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NBME 29 (Original Questions) Full Step 1 Walkthrough & Explanations (Mega Compilation) — Transcript

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0:00Hello everyone. I've compiled a list of
0:01200 questions that are very important
0:03for you to know by the time you finish
0:04MBME29. Each of these compilation videos
0:06takes about 20 hours of work. And so if
0:08you find this helpful, I would really
0:09love it if you could just like and
0:10subscribe. If you want a guaranteed way
0:11to pass this exam, visit ivytutoring.net
0:14to get access to a tutor from Harvard
0:15Medical School. Let's dive into question
0:17one. Here we have a 35-year-old man
0:19brought to the emergency department
0:20after collapsing after multi-day
0:22wilderness survival challenge. Fun fact,
0:23that was my first mayor badge as a Boy
0:25Scout, the wilderness survival one. He
0:27has not eaten in 4 days and reports
0:29dizziness and fatigue. Physical exam
0:31shows dry mucous membranes and mild
0:33orthostatic hypotension. His breath has
0:36a fainty fruity odor. Blood glucose 61.
0:39Bicarb 20. Annion gap 16. We got some
0:42positive ketones. Urine analysis is also
0:44positive for ketones. There's no glucose
0:46in the urine. Which of the following
0:47most directly contributes to the ketone
0:49body formation in this patient's current
0:52state? So 35year-old man, he's got 4
0:55days of starvation. What we need to know
0:56for this question is that the brain can
0:58run on fat in a way. During prolonged
1:00fasting, the body burns fat for fuel,
1:02but the brain cannot use fatty acids
1:05directly. Instead, your liver converts
1:08that fat into ketone bodies. So, thank
1:10you, liver. And that reaction can take
1:12place because of the buildup of acetal
1:14COA from fatty acid oxidation. But
1:16there's a catch. The TCA cycle slows
1:19down because oxalacetate is diverted to
1:21make glucose. So all that acetal COA
1:24right here piles up and gets shunted
1:26into ketogenesis. And so this patient
1:28after days without food shows the signs
1:30of fruity breath, low glucose, and
1:33positive ketones. This guy's body is
1:35running low on glucose cuz he's starved.
1:37Or you'll see untreated type 1 diabetes.
1:40So it has to have another fuel source,
1:42and that's where the ketone bodies come
1:43in. But if your body has no insulin, the
1:45body's like, "Oh my gosh, I'm starving."
1:46And then fat gets broken down. Fatty
1:48acids go to the liver. And normally
1:50acetto COA enters into the TCA, the KB
1:52cycle. But during fasting or diabetes,
1:55oxylacetate is used for gluconioenesis.
1:57And that means the TCA cycle is going to
1:59be slowing down. So the result is, oh my
2:01gosh, we got all this acetal coa. It's
2:04just sitting around. And that's when the
2:05liver converts the extra acetal coa
2:08into, wait for it, ketone bodies. So we
2:11got a dude has eaten. No glucose. No big
2:13deal. Let's burn fat. Check it out. We
2:15just made acettocoa and normally that
2:16goes to the TCA cycle to make energy.
2:18But during fasting or diabetes, the body
2:21uses oxalacetate to make sugar and this
2:23is a process you guys know called
2:24gluconioenesis. And so there's not
2:26enough oxalacetate to go through the KB
2:29cycle. Uh-oh indeed. And so all this
2:31extra acetal COA has nowhere to go. So
2:34the liver turns it into ketone bodies.
2:37So why are these ones wrong? Impaired
2:39hypatic uptake of glucose. That's seen
2:41in type 1 diabetes but not starvation.
2:42Ketogenesis is driven by acetal COA
2:45availability. Decrease NADH to NAD+
2:48ratio. Actually, the opposite would
2:50happen. Beta oxidation increases NADH.
2:54I want you to think of NAD+ like a
2:56sponge that just picks up electrons. I
2:58want you to think of NADH like the used
3:00version. It's full of electrons. And so
3:02this ratio, that is to say NADH to NAD+,
3:05tells us how much electron carrying fuel
3:08is available for energy reactions in the
3:10cell. And during fat breakdown, also
3:12known as beta oxidation, it creates
3:14acetal coa NADH and FADH2. And so this
3:17electron carrying fuel availability
3:19ratio is going to be elevated. You're
3:21making more of NADH. And high NADH to
3:25NAD+ ratio slows down the KB cycle
3:28because NADH tells the cells, "Hey guys,
3:30we got enough energy. Look at me. I'm
3:31full of electrons." And this causes
3:33acetal coa to build up. Why? Cuz it
3:35can't enter into that TCA cycle as
3:37easily. And what happens as we now know
3:40to the extra acetal coa? Well, it gets
3:42shunted over to make some more ketone
3:43bodies. How about inhibition of
3:45carnitine transport to the mitochondria?
3:47That would block fatty acid entry.
3:48There'd be less fate oxidation. So
3:50that's the opposite. And e enhanced
3:52glycolysis. That would be suppressed in
3:55fasting. Hpatocytes prioritize
3:56gluconneogenesis over glycolysis. And in
3:59case that's confusing, glycolysis is the
4:01breaking down of glucose to pyuvate to
4:04make energy. It's what the body does
4:06when there's plenty of glucose
4:07available. But if you're fasting or you
4:08have type 1 diabetes, there's not enough
4:10glucose inside the cell. And so this
4:12solution, our body's solution for
4:14turning glucose into pyuvia to make
4:15energy is not a good one anymore. And so
4:18the liver is like, "Oh my gosh, let's
4:19switch gears. Let's stop breaking down
4:21glucose." Glycolysis and we'll start
4:24making glucose. And that is known as
4:26gluconneogenesis.
4:28So for step one, you need to know you
4:30are not you. When you're hungry, fed
4:32state, glycolysis is on. You're burning
4:34that glucose. It's off here and on here.
4:38If you're fed, insulin is high. And if
4:40not, insulin is low and glucagon is high
4:42because gluconogenesis is on. So
4:45enhanced glycolysis and hpatocytes is
4:48incorrect because the liver isn't
4:50breaking down glucose. It's trying to
4:52make more. Are you ready for question
4:53number two? A 70-year-old woman underos
4:56evaluation for chronic aspiration
4:57pneumonia during neurologic testing. A
4:59cotton swab is used to gently stimulate
5:02the left side of her or ferinx, but no
5:04gag reflex is elicited. What's damaged
5:06is the glossopherringial nerve. That's
5:07the afrant limb of the gag reflex. So if
5:10you touch one side of the throat and
5:11there's no gag reflex, but the other
5:13side works fine, then what's missing is
5:15the aference sensory limb. Aference is
5:17for your senses. I like to remember this
5:19by thinking, "Wow, that affected me. I
5:21felt that sensory and that's carried out
5:23by the glossophrenial nerve. So cranial
5:25nerve 9 detects the stimulus on the back
5:27of the throat and it passes it to
5:29medulla. And then the vagus nerve, which
5:31is cranial nerve 10, contracts the
5:33muscles causing the gag. And if one side
5:35does not sense anything but the muscles
5:37still work well when triggered from the
5:39other side then it's an afrant problem.
5:41Cranial nerve 9 glossopherringial. Now
5:44there's a lot more you could see on test
5:45day. So let's explain some of these
5:46other things. The high yield buzzy
5:47stuff. Anytime you have apps and gag,
5:49you should think of glossophringial and
5:51Vegas apherrant eent. If for instance
5:54this question were to ask about cranial
5:55nerve 10 being damaged, then the
5:56stimulus would be detected but no motor
5:58response would happen. The
6:00glossopherrenial does sensory from the
6:02ferings and taste to the posterior 1/3
6:04of the tongue. There's something called
6:06the jugular fammen syndrome. That's if
6:08you have a mass like a tumor metastasis
6:10or schwanoma that compresses the area of
6:12the jugular fammen then you can get the
6:14loss of the 9 10 11. Nine is loss of gag
6:17reflex dysphasia. 10 would be
6:19horarsseness pallet drop uvula
6:21deviation. 11 is a weak shoulder shrug.
6:24You'd have the SCM and the trap
6:25weakness. So if you see horarsseness,
6:27shoulder weakness and a loss of gag
6:29reflex, it's a jugular fammen problem.
6:30Now there's also Wallenberg syndrome
6:32that is caused by an occlusion of the
6:34posterior inferior cerebellar artery,
6:36stroke in the lateral medela. This
6:38affects the 9 and 10 nuclei. So you get
6:40a loss of the gag reflex, but it also
6:42affects the spinalic tract. You get a
6:44contraateral pain and temperature loss.
6:46You also get damage to the vestibular
6:47nuclei. Horner syndrome is super
6:48important. It's the triad of
6:49ipssolateral. So same side signs of
6:51disruption to the sympathetic
6:52intervation to the face. Ttosis, meiosis
6:54and hydrosis. tois means the drooping
6:56eyelid and that's due to the loss of the
6:57superior toarsel muscle which is
6:59sympathetically driven. Meiosis is the
7:00constricted pupils and that's due to the
7:02loss of the pupilary dilator muscle
7:04which is sympathetic. And then
7:05inhydrosis that's the lack of sweating.
7:07So you have decreased sweat gland
7:09stimulation and all those three are on
7:11the same side of the face. So it's a
7:13three neuron chain and all this to say
7:14if the location is a lung apex then
7:16think of a panco tumor and that's
7:18epsilateral her. If it's an internal
7:20corateed artery, then you think of
7:21dissection and that's painful hero
7:22syndrome. And a spinal cord trauma could
7:24be brown sicard syndrome. It's like the
7:26hemise section. But yeah, basically know
7:28that ipsolateral means like the same
7:29side and that's because the sympathetic
7:31fibers do not cross. They stay on the
7:32same side the whole way. So if you knock
7:34out the sympathetic chain on the right,
7:35then all symptoms will also show up on
7:37the right. Okay, just wanted to explain
7:38orange syndrome. And I think this is a
7:40good illustration of the principle. Just
7:42review one part of a question. Zoom out.
7:44Get the whole picture. Cover all the
7:45areas you're weak in. Ready for number
7:47three? So here we have a 58-year-old man
7:49history of hyper lipidmia presented to
7:51the emergency department with a sudden
7:52onset nausea chest tightness dizziness
7:54ECG shows ST elevation in these inferior
7:57leads there's no crackles and clear
7:59jugular venus distension which of the
8:00following arteries is most likely oluded
8:02answer right coronary now this is just a
8:04table you have to memorize 2 three AVF
8:06this is all right coronary artery the
8:08lateral would be 1 V5 V6 AVL that's the
8:11left lateral wall V1 to V4 is covered by
8:14the lad the septal is V1 V2 that's also
8:16the lad but it's the septal branch and
8:17the posterior is V7 to V9, but that's
8:20not on the 12 lead, right? That can be
8:21your RCA or the LCX. And there you see
8:24ST depressions in the V1 to V3, which is
8:26just the posterior. So here's our
8:28diagram. The inferior right here,
8:30lateral leads, inferior, lateral,
8:32septal, anterior. This is a cool
8:33pneumonic 12F looks like inferior. This
8:36shows the magnitude and direction and
8:37lead one. There's the inferior, lateral,
8:39lateral, lateral, septal, antior. Last
8:42one. Inferior, lateral lateral, septal,
8:44antior. Now you might be wondering
8:45what's all the stuff I hear about ST
8:47elevations. Well ST elevations mean for
8:49step one that you have a transmural
8:50inffection. So ST segment increase shows
8:53there's a full thickness injury from the
8:55epicardium to the endocardium. And the
8:57reason why is that dead moardial cells
8:59cannot repolarize. You have persistent
9:01deolarization and so the baseline shifts
9:03down and the ST segment looks elevated
9:04on the EKG. This is caused by an acute
9:07thrombotic occlusion of a coronary
9:09artery and so you have complete blockage
9:10and that means there's no blood flow. So
9:12it starts with eskeemia then it causes
9:13injury and then there's an infar
9:15cascade. Now if this question asked
9:16about like the anterior STE with
9:18hypotension then you'd say okay it's
9:19anterior 1 to4 L. If they asked about ST
9:23depression then it' be the posterior MI.
9:24If it's a young Asian male then it's
9:26bugata a mutation that causes
9:28dysfunctional sodium channels and it
9:30leads to polymorphic ventricular
9:32ticardia. Kind of like torsads but it's
9:33seen in young Asian males. At least
9:35that's how they'll ask about it on step
9:37one. And that has a risk of sudden death
9:38by the way. All right question four.
9:39where we have a 55-year-old man with
9:41familial cholesterolmia. They started on
9:43new medication after he develops a
9:44statin associated myalgis. Basically,
9:46he's got some aches and pains in his
9:47muscles and tendons. The drug works
9:49locally in the GI tract is not absorbed
9:50systemically. Over time, the LDL levels
9:52decline, but he begins experiencing
9:54bloating and fats soluble vitamin
9:55deficiencies. Which mechanism explains
9:56the lipid lowering effect of the agent?
9:58Okay, so it's not statin, it's something
10:00else. And before we dive into the
10:01correct answer here, I think it's
10:03important to know the lay of the land.
10:05There's something called a very low
10:06density lipoprotein. That's the fat
10:08delivery truck that your liver sends out
10:10to deliver triglycerides. I mean, look
10:12at all those L's. You can tell that it's
10:14made by the liver. L li liver. It's
10:16metabolized into LDL, which is more
10:18cholesterol-rich. The purpose is to
10:20deliver triglycerides to muscle, fat,
10:22and tissues. This eventually turns into
10:24LDL, and that carries mostly
10:26cholesterol. And before we dive into the
10:28answer, you'd also need to know what
10:29LCAD is. Now, this is the highdensity
10:32lipoprotein that makes cholesterol safe
10:34to carry. It makes HDL useful. It turns
10:37the trash cholesterol into packable
10:39cholesterol that HDL can return to the
10:42liver. So very nice of LCAT to do that
10:43for us. We're almost there. What about
10:45cholesterine? Well, that's the bile acid
10:47resin. It binds the bile acids in the
10:49gut so that you can poop them out. And
10:50this forces the liver to make more
10:52cholesterol. So the effect is decreased
10:54cholesterol in the blood. So think of
10:55this as you're flushing out the bile. So
10:57the liver panics and uses more LDL
10:59cholesterol to make bile. And that means
11:01your LDL is going to drop because you're
11:03flushing it out and you need that stuff.
11:04You know, it's like tissues. Yes,
11:05they're useful if you're sick, but then
11:07you're used up and you have less tissues
11:08in the box after you've been sick. All
11:10right, so this guy right here delivers
11:12dietary triglyceride to the body. It has
11:15tons of triglyceride, very low density
11:17that delivers the liver made
11:18triglycerides. So has some cholesterol
11:20but lots of triglyceride. There's LDL
11:22and LDL delivers cholesterol to the
11:24tissues and this is mostly cholesterol.
11:26And there's HDL and that picks up
11:28cholesterol from the tissues to the
11:29liver. So it has cholesterol esters. And
11:31then there's LCAT and that makes
11:33cholesterol packable for HDL. Elcat's
11:35such a nice guy to help out the HDL like
11:36that. So, which mechanism explains the
11:39lipid lowering effect of this agent?
11:41There's a fat soluble vitamin deficiency
11:43and that's due to the loss of bile.
11:45Okay, so that's the first clue. We also
11:46know this acts on the GI tract. It's not
11:48absorbed. So, we're binding those bile
11:49acids and we're excreting them in the
11:51feces. And as we spoke of before, this
11:53causes the increased LDL receptor
11:55expression. So, the liver is pulling
11:56more cholesterol from the blood. Why?
11:58Because the liver loses bile acids and
12:00it must make more. So, it makes up its
12:03own cholesterol stores. So the end
12:04result is going to be an upregulation of
12:06LDL receptors because this is a bile
12:07acid resin. Choleistramine that's the
12:09drug that's what we're introducing here
12:10acts as the binding site of bile acids
12:12increasing their excretion and so we
12:14compensate by making more LDL receptors.
12:16LCAT inhibition would disrupt the HDL
12:19maturation. But basically we need to
12:20know this is bile acid resin which binds
12:22bile acids in the gut and it forces the
12:25liver to use its cholesterol stores to
12:26make more bile. So it lowers LDL by
12:29increasing LDL receptor expression. And
12:31the drug's non-absorbed gut limited
12:33nature causes the GI effects and vitamin
12:35K deficiency which explains things like
12:37prolonged PT for instance they could
12:39tell you about or any of the ADK vitamin
12:42deficiencies because that bile acid
12:44resin is gone. So the most important
12:45parts of this question are we know bile
12:47acids are made from cholesterol in the
12:48liver. We know they're stored in the
12:49gallbladder and they're released in the
12:51datadum after a fatty meal and their job
12:53is to emulsify fats, right? It helps you
12:55absorb dietary fats like ADK.
12:57Cholesterine binds bile acids in the
12:59gut, prevents reabsorption in the
13:01terminal and you poop out bile acids
13:03instead of recycling them. So there's
13:05less bile in the gut and the fat cannot
13:07be emulsified properly and so you get
13:09poor absorption of vitamins like ADK fat
13:12soluble vitamin deficiencies. A you know
13:14causes night blindness, dry skin, D bone
13:16softening, ricketetts, ostealia,
13:17hypocalcemia, e neuropathy, hemolyic
13:19anemia, it's an antioxidant and K
13:22bleeding time. Next practice question,
13:2360-year-old woman underos routine
13:24follow-up after completing adjacy.
13:26That's like the secondary therapy for
13:28estrogen receptor positive breast
13:29cancer. She's taking daily oral
13:31medication that has been shown to
13:32significantly reduce the risk of
13:34infection in women with hormone
13:35sensitive tumors. She has not
13:36experienced hot flashes. Which of the
13:38following best describes the mechanism
13:39of action of the drug that she's taking?
13:41Trying to hide the answer. Don't look.
13:43But what should immediately come to mind
13:44here is temoxifen and relax. These are
13:46selective estrogen receptor modulators.
13:49That's why when I was creating these
13:50questions for the first time, I wrote
13:51down SERM because this is a selective
13:53estrogen receptor modulator question.
13:55And these guys are cool because they're
13:56agonist in some tissues and antagonist.
13:58So you should be thinking of two things.
14:00One breast tissue and two the
14:01endometrium. One in breast tissue both
14:03are antagonists. So temoxifen and
14:06relaxophene block estrogen receptors in
14:08the breast. So this is used in breast
14:09cancer prevention or treatment. And our
14:11goal is to stop the estrogen driven
14:13tumor growth. Okay. So they both work on
14:15the breast tissue. However, the
14:17endometrium is different. Tmoxifen is an
14:19estrogen agonist in the endometrium.
14:22Uh-oh. It increases the risk of
14:23endometrial hyperplasia. Relaxophene
14:25however is an antagonist in the
14:26endometrium. So there's no increased
14:28risk of endometrial cancer and it's
14:29safer in postmenopausal women. And the
14:31way to remember this way that I like to
14:32remember this is T stands for terrible.
14:34It's terrible because it can cause the
14:35indometrium problems. And then R is
14:38respectful because it does not cause
14:39those in the endometrium. I don't know
14:41whatever worked right but they both are
14:43agonist for bone protection. So it's
14:46also used in osteoporosis prevention in
14:48postmenopausal women and especially is
14:49favored here because of the lower cancer
14:51risk. Right? So, it's protective of the
14:52bone and they do protect bone, but they
14:54cause clots to form. Remember, they're
14:56selective estrogen receptor modulators
14:58and so they mimic estrogen in some
14:59tissues and block it in others. And so,
15:01in the bone, estrogen is protective,
15:02right? And so, the serms are mimicking
15:04that less we forget estrogen inhibits
15:07osteoclass. It's like guys, we got to
15:09prevent that bone absorption and ser as
15:12estrogen agonist at these bone
15:13receptors. And so, tmoxifen and
15:15relaxophine increase bone mineral
15:17density. And so, it's used for
15:18osteoporosis. Now, estrogen's all over
15:20the body, right? And in the liver,
15:21estrogen is a proagulant. Estrogen
15:23increases the synthesis of clotting
15:24factors. I don't know if you knew that.
15:26Which ones? 27910. And both temoxifen
15:28and roxophene act as agonists. The
15:30result is increased clotting factor
15:31production. So you have an increased
15:32risk of DVT. Wild, huh? So the bone
15:35estrogen agonist. Liver estrogen
15:37agonist. Breast estrogen antagonist,
15:40right? So you decrease that cancer
15:41growth. Endometrium tomoxifen is
15:44terrible. It's an agonist there.
15:45Increased cancer risk, but it's an
15:47antagonist there. It's respectful of the
15:48endometrium. Hopefully that made tons of
15:50sense and that's why your answer is
15:51competitive blockade of estrogen
15:52receptor in the breast tissue. This is a
15:54serum. That's what it does. You can look
15:55at these associations and these
15:57buzzwords. Feel free to pause, but we're
15:59going to be moving on, folks. I want
16:00this to be as efficient and high yield
16:01as possible. My goal is you guys are
16:03sitting at home like, "Oh my gosh, I
16:04can't study anymore." And then you found
16:05this YouTube channel, you're like, "Oh,
16:06sick. Let's get the popcorn going."
16:07Okay, question six. We got a new nasal
16:09spray, baby. Seasonal allergic renitis.
16:12We got 200 adults randomly assigned to
16:14receive either the spray or the placebo.
16:16What's the answer? This is a randomized
16:17control trial. There's a lot of anxiety
16:19to pick something as simple as a control
16:21trial, which is like the backbone of all
16:23of science, randomized control, the gold
16:25standard. But the takeaway here on step
16:26one is pick what you're familiar with.
16:28They're testing high yield topics at the
16:29end of the day. If you keep picking
16:30things that you're familiar with and
16:31have confidence, then you're going to do
16:32well. Let's say they give you a weird
16:33one, case control. Well, for this one, I
16:35want you to think of the Odds ratio. For
16:37example, here you'd compare patients
16:39with lung cancer versus without, and you
16:41check their prior smoking status. So,
16:42you start with the outcome. Another odd
16:45odd outcome. See, I just this is how I
16:48remember it. O for case control. Another
16:51one they can give you as a crossover
16:52study. That's where each subject gets
16:54both treatments and then they're
16:56separated by wash out period. So each
16:57subject is essentially their own
16:58control. And so one group would get drug
17:01A and then drug B and then the other
17:03group gets the reverse. That's
17:04crossover. I think of Bojack Horseman.
17:06Wow. Is this a crossover episode only
17:07for both switching and reversing? That's
17:09the answer that I get Bojack in my mind
17:10as I study for step one. Rather Mr.
17:11Peanut Butter. I digress. That's
17:13randomized control. Cross-sectional is a
17:15snapshot in time. It measures the
17:16exposure and outcomes simultaneously.
17:18And what they're always going to test
17:19you on for this one is the prevalence.
17:20And there's no temporality for this. So
17:22for an example, they could survey 5,000
17:23people on smoking and the current lung
17:25function today in time. That's
17:27cross-sectional. Prospective cohort
17:28study starts with the exposure and then
17:30you follow forward. In this one, you
17:32study risk factors. Risk factors for
17:34cohort. We assess the relative risk for
17:35perspective cohort. That's the easiest
17:37way to remember this. Once I had that in
17:39my brain, these questions became super
17:40easy. All right, for the next question.
17:42Whenever you see these images, you
17:44should think of mono sodium urate. These
17:46are gout. For some reason, it looks like
17:48Star Wars. I don't know. But yeah, this
17:49is gout. You see it on test day, you
17:51just click it immediately. And here we
17:52have a 58-year-old man who's got acute
17:53pain and swelling of his right ankle
17:55that began overnight. He has a history
17:56of hypertension and chronic kidney
17:58disease. Examination shows arithmatis,
17:59tender and warm ankle joint with limited
18:02range of motion. Aosentesis is
18:03performed. Synovial fluid has 25,000 or
18:06greater white blood cells and
18:07needle-shaped crystals that appear
18:09yellow. Okay, this is gout. The answer
18:10is C. But equally interesting are the
18:12buzzwords and associations for other
18:13answer choices. If they said
18:15needle-shaped negatively bringent
18:16crystals negative needle needle negative
18:19and gout is a negative condition you do
18:21not want it pseudo gout a little bit
18:22more positive. I don't know that's just
18:23the way I think about it. If they show
18:24enveloped or dumbbell shaped then it is
18:27going to be calcium oxalate and that's
18:28often seen with ethylene glycol
18:30poisoning. If you see cholesterol
18:32clefts, that's chronic inflammation
18:33often rheumatoid eusions in atheromomas.
18:36By the way, an atheroma, also known as
18:38an atheromatus plaque, is a buildup of
18:39fats and cholesterol and other
18:40substances in the inner layer of the
18:42artery. So calcium pyrophosphate that's
18:44linked to aging, maybe hemocromattosis,
18:46hyperarathyroidism. These conditions
18:48cause inorganic pyrophosphate levels or
18:50calcium levels and they promote the CPPD
18:53crystal formation. That's calcium
18:54pyroofhosphate deposition disease.
18:56calcium oxalate that's seen with
18:57ethylene glycol poisoning vitamin C
18:59overuse or Crohn's disease. Three, you
19:01have fab malabsorption that increases
19:02the oxalate absorption. Our answer is
19:04sodium monurate and that's just gout,
19:07right? It's associated with cellis, high
19:09purine turnover, tumor lis syndrome or
19:11alcohol use and cholesterol is just
19:12going to be long-standing fusions with
19:14the rheumatoid arthritis due to the
19:15chronic synovial inflammation. So let's
19:17see what these explanations are. Classic
19:19gout negatively by fringen. Calcium
19:21pyrophosphate has the romboid shaped.
19:23Kidney stones would be seen with calcium
19:24oxalate, not the joints. Cholesterol is
19:26found in lipid diffusions. Hydroxy
19:28appatite would be calcific tendinitis.
19:30Now the last thing that might test you
19:31on with this is oxalate is a normal
19:32byproduct of metabolism right from
19:34oxalate vitamin C. And it's usually
19:36excreted in the urine after it binds to
19:38calcium in the gut. So it's got to find
19:39its friend calcium. And if oxalate
19:41levels are too high or if calcium is not
19:43available, then it'll form insoluble
19:44calcium oxilate crystals in the renal
19:46tubules. And these crystals can obstruct
19:48the tubules and it causes acute tubular
19:51necrosis or renal failure. And this is
19:53seen in antifreeze ethylene glycol
19:54poisoning, right? Because it's
19:55metabolized by alcohol dehydrogenase
19:57glycolate to form which then leads to
19:59oxalate. So anytime you increase oxalate
20:01or decrease calcium, you have to be
20:02worried about these guys cuz this is
20:03going to be metabolized oxalate and you
20:05have excess oxalate load. Then you have
20:06crystal formation. In Crohn's disease,
20:08the fat binds calcium in the gut. So you
20:10have less calcium to bind to the
20:11oxalate, right? The fat is taking care
20:13of the calcium in Crohn's and so
20:14freeoxide is now absorbed in the colon
20:16instead of being excreted and that leads
20:17to secondary hyperoxileria and you get
20:20kitty stones. So envelopes or dumbbell
20:22shaped. Oh and by the way why is it high
20:25an gap metabolic acidosis? That's
20:26because obviously ethylene glycol causes
20:28the formation of these acids and these
20:30are organic acids and so they donate.
20:32What do acids do? They donate. Thinking
20:34back to organic chemistry in college
20:35hydronium ions and they lower the pH and
20:37they consume bicarbonate. So it
20:38increases the acid load. So you deplete
20:40bicarbonate causing metabolic acidosis.
20:42And that's your like mud piles, right?
20:44Methanol, deformic acid, uremia, renal
20:47failure, diabetic keto acidosis. I
20:48should probably write this down. Mud
20:49piles,
20:51methanol, uremia, diabetic keto
20:53acidosis, propyline glycol, bing bing,
20:57and iron, lactic acidosis, ethylene
20:59glycol, and S stands for salicellate.
21:01That's your late phase. So yeah, watch
21:02out for hypocalcemia crystals in the
21:04urine with calcium oxalate. You treat
21:06with measol or ethanol. Those are
21:08competitive inhibitors of alcohol
21:09dehydrogenase and also bicarbacidosis
21:11and you can even do hemmoialysis if it's
21:14super severe. So yeah, fpazol isol is
21:15the antifreeze antidote. That's pretty
21:17much all you need to know about on step
21:18one, but basically it just blocks that
21:19first step. You're preventing the
21:21formation of the toxic metabolites.
21:22You're inhibiting alcohol dehydrogenase.
21:26All right, next we have a 13-year-old
21:27girl brought to the clinic for school
21:29physical. She's got concerns that she's
21:31significantly shorter than her
21:32classmates. She's always been the small
21:34size and her mom didn't start menrating
21:35till 16 in the fifth percentile weight
21:3730th. This is a late bloomer and our
21:39condition causes a temporary delay in
21:41the skeletal growth. You have normal
21:42predicted adult height. It's just slow
21:44but consistent. Now, if the growth curve
21:46were to flatten, so like if it's not
21:47growing consistently, if it like
21:48flattens, then that's going to be an
21:49endocrine or a systemic illness. But if
21:52you have normal velocity but low
21:53percentile, then it could be familiar
21:55short stature. So familiar short
21:57stature, that's like normal velocity.
21:59Here we have delayed, so it's
22:00constitutional. Next question we have, a
22:0224 year old woman has a 5-day history of
22:04joint pain, blotchy rash of her upper
22:06limbs. She started treatment with a
22:07mouse derived monoconal antibbody for
22:09severe alastic anemia. She's got tender
22:11swollen wrist and knees. Arithatus
22:14maculopapular lesions on her chest and
22:15forearms. Lab studies show lucasite
22:17count of 7,800, ESR of 55, compliment C3
22:21of 68, which is low. What describes the
22:23mechanism? The answer is immune complex
22:24deposition. She's got serum sickness,
22:26which is type 3 hypersensitivity. It's 1
22:28to two weeks after you have a foreign
22:29monoconal antibbody. We have fever,
22:31alphalgia, rash, low compliment.
22:34Alpharalgia is just pain at your joints.
22:35By the way, here are the other answers
22:36and why they're wrong. Now, there's a
22:37pneumonic that you can know for these
22:39type of hypersensitivity reactions. Acid
22:41cuz type one is allergy or anaphylactic.
22:44Two is cytotoxic. That's antibbody
22:46mediated. Three is the immune complex.
22:48And then four is delayed. That's T- cell
22:50mediated. So the aniflactic has mediated
22:53activation of mass cells and this
22:54requires a prior sensitization. So here
22:57you have histamines, lucro
22:58prostaglandins they cause vasoddilation
23:00bronco spasms and the onset here is just
23:01minutes. So think like a bee sting,
23:03peanuts, shellfish, penicellin, allergic
23:05rhinitis like hay fever, asthma, eczema
23:08like attopic dermatitis, uticaria which
23:10is hives, food allergies, things like
23:11that. Type two is a cytotoxic antibbody
23:13mediated reaction and the mechanisms
23:15here are through IGG and IGM and these
23:18bind to the antigens on cell surface and
23:19they trigger compliment activation which
23:21is ITP. You could also have receptor
23:23related problems like Graves disease,
23:24myosthenia gravis, pimpagus vulgaris,
23:25that's the anti-esmogleon. So pimpus
23:28vulgaras is the antid-desmagleen. Bolis
23:30pmpagoid is anti-hemism and those are
23:32all type two. Then there's type three
23:34that's where you actually form the
23:35complexes. These guys are IGG, the
23:37antigen antibbody complexes that form in
23:39circulation and they deposit in the
23:41tissue. So they activate your compliment
23:42system and that's why we have the low
23:43compliments in this question. Attract
23:44the neutrfils inflammation of tissue
23:46damage and the onset is like days. So
23:48here's serum sickness, right?
23:49antivenenom monocal antibbody penicellin
23:52that's the stuff you think of another
23:54big one too is going to be lupus the DNA
23:56antiDNA complexes that form postropocal
23:58glam lifritis polyritis nosa
24:01hypersensitivity pneuminitis that's like
24:02farmer's lung all these immune complex
24:04depositions complent activation lowc3
24:07neutrfils fibonoid necrosis vasculitity
24:10these are all type three
24:11hypersensitivity reactions type four is
24:13the delayed cell mediated type that's
24:15where you have the CD4 TH1s or the CD8
24:18cytotoxic T- cells and there No
24:19antibodies involved. This is macrofage
24:21and cytoines that drive the
24:22inflammation. The onset is 48 to 72
24:23hours. So here you think of like a skin
24:25test. Tuberculosis is a skin test.
24:27Contact dermatitis. That's like poison
24:28ivy, nickel, latex, even immune. You
24:31could also have some autoimmune problems
24:32like type 1 diabetes. That's your beta
24:34cell destruction by your CD8 positive
24:36tea cells. Multiple scerosis. That's
24:38where you have tea cells against your
24:39myin basic protein. Hashimotoyroiditis,
24:42gon beret, ciliac and graph rejection.
24:44So like acute transplant, graph versus
24:46host disease. You have a delayed
24:48response. It's T- cell mediated. There's
24:49macrofase activation granulomaas, no
24:51antibodies, and enduration after 48
24:53hours. So that's everything there is to
24:54know about type 1, 2, 3, and four. And
24:56then you look at this one, you go, okay,
24:57we've got serum sickness. That's a type
24:59three immune complex. This is one to two
25:00weeks after the exposure of monocomal
25:02antibodies. They have the mouse
25:03monocomal antibbody. And so you have low
25:05compliments. This is definitely going to
25:06be activation. And so our answer is C.
25:08That's how you do it. All right. For
25:09question 10. Here we have a 55-year-old
25:11man with a 5-year history of rheumatoid
25:12arthritis. Has worsening fatigue over
25:14the last 3 months. He denies blood loss,
25:15no change in diet, takes methtoresate
25:17and NSAIDs. Lab results show all of this
25:19good stuff. What's the cause of his
25:21anemia? The answer is increased hepsy
25:23mediated iron sequestration. This is
25:25anemia of chronic disease. You know this
25:26is also known as anemia of inflammation.
25:28Very common tested cause of normocitic
25:31microitic anemia especially in
25:32hospitalized or chronically ill
25:34patients. So they're probably going to
25:35have like lupus. They're going to be on
25:36some cortical steroid prennazone for
25:37instance. And this is where you're
25:39trapped in the storage, right? You have
25:40anemia of inflammation. And what's
25:42interesting about this guy is that the
25:43iron is totally present. It's just like
25:44locked away. And interestingly, you have
25:46increased heepsidon from the liver which
25:49inhibits feraporin. Basically, iron is
25:51present, but you can't use it cuz
25:52heepsiden is a peptide hormone that's
25:54produced by the liver especially during
25:55inflammation. This is triggered by IL6.
25:58So, inflammation time, right? And it
25:59binds heepsidon to feraportin and that
26:01that binding triggers internalization
26:04and it degrades the feraportin and it
26:05prevents the iron export into the
26:07plasma. Serum iron even though there's
26:09increased feritin. And I like to think
26:11of TIBC as how much your body wants the
26:13iron. It doesn't cuz it has a lot of it.
26:15So it's low as well. And the MCV is
26:17normal to low. So feraportin is the only
26:20known cellular iron exporter. And so
26:22heepsidon is the master iron regulator.
26:24So it's like the lock on the iron gate,
26:26right? You have inflammation and that
26:27locks and it tightens things. So imagine
26:29your dude right here, he's an interasite
26:31in the gut, right? He's just absorbing
26:32dietary iron and he sends the iron to
26:35the blood. Well, heepsidon triggered by
26:37the IL6 active inflammation is like,
26:39"Hey bud, stop that." And so heepsidon
26:41blocks that export. Or imagine you got
26:42another guy. He's a macroofage and he's
26:44like, "I'm going to recycle iron from
26:45the scinesscent red blood cells. I'm
26:47going to release the iron." Well,
26:48Hepsidon goes, "Let me take that. I'm
26:50going to trap that iron." And imagine
26:52our last dude is like a hypatocite. He's
26:53like, "Oo, I'm going to store the iron.
26:55I'm going to regulate the plasma iron."
26:56And then Hepsidon's like, "Nope, you're
26:58not going to release that, bud." So,
26:59it's just like stopping things. It's
27:00binding to feraportin and it's just
27:02halting things and it's being trapped.
27:03And so you're withholding iron from the
27:05pathogens, right? From from an
27:07evolutionary standpoint, that's what
27:08we're doing cuz pathogens need iron,
27:10too. But and so your body's like, "Oh my
27:12gosh, I got all these pathogens. I'm not
27:13going to share my iron." But in chronic
27:14inflammation, right? This protective
27:16mechanism, which is awesome. Thank you,
27:17Evolution. Is now maladaptive. And you
27:20have anemia, right? You need iron, too.
27:22Oh, man. The body's so funny. But yes,
27:24this is a hepiden mediated blockade of
27:27the iron release. All right, folks. That
27:29does it. We finished the first 10. I'm
27:30going to take a break, maybe do a couple
27:32curls with my calcium oxalate dumbbells.
27:33And I want you guys to stretch your
27:35legs, do something fun, treat yourself.
27:37You're going to do great things with
27:38your life. Just know you're going to get
27:39through this. You will get through this.
27:40It takes a little bit more time. Who
27:42cares? Life is long and short at the
27:43same time. Enjoy yourself. Like and sub
27:45if you like this channel. Hoping to give
27:46you guys highquality resources. We got a
27:48lot of things. Check out the link in the
27:49description if you want tutoring kind of
27:51like what we did today, but more
27:52personalized to you. Guaranteeing that
27:53you're going to get a pass on step one.
27:55Click the links in the description. You
27:56can get an inerson tutor. And we're also
27:58launching some courses soon. Take care
27:59y'all. We'll see you soon. Hello
28:01everybody. I recorded two hours of
28:02footage and it all was muted. So, really
28:06quickly, I'm going to blitz through MBME
28:0829. All original questions, everything
28:10you need to know. We're going to go from
28:1223 all the way to 50. All right, let's
28:14dive into it. In this question, we have
28:15a 70-year-old man undergoing resection
28:17for stage 2 pancreatic cancer enrolled
28:19in a long-term perspective trial
28:22tracking postoperative survival. The lab
28:25below shows the proportion of patients
28:26alive at the start of the year and how
28:27many survived through the following
28:29year. All right. And then it progresses
28:30through and they're asking us, hey,
28:32what's the probability he'll survive
28:34through year four? And the answer is
28:35literally just C. It's exactly this
28:37value. Now, what's interesting is this
28:39is a Kaplan mayor survival curve and
28:40this is a non-parametric statistical
28:43approach where you just analyze the time
28:45to event data and it's used for survival
28:47analysis. Parametric would be like a t
28:49test, a nova, linear regressions, right?
28:51You assume normality, linearity, all
28:52that stuff. Non-parametric is the Keplan
28:55mayor survival curve like in this
28:56question. So really easy. Parametric
28:59just means you're fitting your data to a
29:00mold. Non-parametric is you're just
29:02letting the data decide the mold. And
29:04that in itself is even overkill. All you
29:06need to do is just kind of look at this
29:07little table and say, okay, you're four.
29:09It's here. Boom. Boom. When you're
29:11dealing with biosats, I had somebody ask
29:12me, "Hey, can you do bioats questions?"
29:14And I said, "Yes, soon." Biostats, don't
29:16overthink it. Just memorize the formulas
29:18and then have the confidence to be able
29:19to select the answers because they're
29:21usually pretty easy or they're
29:22formulaic. They don't expect you to do
29:23large calculations. That's biostats.
29:25Next. All right, in our next question,
29:27we have a 5-year-old girl brought to the
29:28clinic for swelling around her eyes and
29:29abdomen that developed over the past
29:30week. Her parents report she had mild
29:32upper respiratory infection two weeks
29:34ago and someone update the image to show
29:36like a young boy or young girl. You can
29:38see right there in the image that's the
29:40demographic we're talking about. And on
29:41exam, we have parallel edema, distended
29:43abdomen, shifting dullness and normal
29:44blood pressure. Your analysis shows four
29:46plus protein but no hematia. Serum
29:48creatinin is normal. Albamin is 1.6.
29:50Cool. And this is the most important
29:52part I think reveals widespread affement
29:53of pot foot process. This is minimal
29:56change disease. Now the case breakdown
29:57here is definitely going to be you do
29:59not have blood in this disease. It's
30:00protein area hypoalmia. What does that
30:03mean? That's when you have low levels of
30:05albmen in the blood and it causes the
30:07fluid to leak out of the blood vessels
30:08and accumulate in other body tissues.
30:10Right? So you're going to have like the
30:11swelling in the legs, the abdomen, the
30:13lungs. And this is usually because of
30:14like a liver disease or increased loss
30:17like in kidney disease and and even
30:19burns. And the treatment is really just
30:20focused on managing the root cause. So
30:22hypoalenemia that's going to be minimal
30:24change disease and on light microscopy
30:27this is super super important it looks
30:28totally normal if you see normal on
30:30light microscopy you see a facement of
30:32the potytes click it move on that's
30:34super easy points on test day and it
30:35responds super well to steroids outport
30:38syndrome hearing loss is what you'd see
30:40with that splitting of the GBM focal
30:42segmental glamial sclerosis this is
30:43going to be super common in Africa
30:44descent HIV but you would see segmental
30:47sclerosis not minimal change hence
30:49minimal change disease membranous
30:51neuropathy That's another nefertic
30:52syndrome and it's thickened GBM and also
30:55you have the sub epithelial deposits in
30:56adults. So minimal change disease really
30:59think of in the children and IGA
31:01nephropathy is hematia post infection.
31:03All right. In our next question we have
31:04a 42-year-old woman undergoing
31:06exploratory lprotomy. Leparottomy is an
31:08incision into the abdominal cavity in
31:10preparation for surgery. It's given
31:11under general anesthesia. During the
31:12procedure she receives introvenous
31:14medication medication to facilitate
31:16relaxation. breathing ceases despite
31:19preserved spontaneous frenic nerve
31:21firing. Her pupils are reactive and all
31:22that stuff. However, no thoracic
31:24abdominal excursions are noted. Which of
31:26the following drugs was administered?
31:27Pecurronium is the answer. So the setup
31:29in this question and I'll zoom in to my
31:30notes when I did this the first time is
31:32the air flow is stopping right and the
31:34diaphragm is not moving and the frenic
31:36activity is still continuing right. So
31:37what does that mean? That means that the
31:38brain and the nerves are still firing
31:40but the abdominal pressure that stops
31:42changing. What does that mean? The
31:43muscles are not responding. So here's
31:45like the the key logic. If the nerve
31:47signal is still firing, but the muscles
31:50don't move, then the block has to be at
31:52the neuromuscular junction, right? And
31:53that's post synaptic. So that's exactly
31:55what a non depolarizing neuromuscular
31:58blocker is going to do. And so boom,
32:00there's our answer. We pick our
32:01non-polarizing neuromuscular blocker and
32:03it competitively inhibits acetylcholine
32:04at the nicotinic receptors in the
32:06neuromuscular junction. So the frenic is
32:07going, diaphragm can't contract. Sooline
32:09would have initial faciciculations. It's
32:11a deolarizing blocker. So you'd have
32:13brief muscle activity before paralysis,
32:15not just cessation prior to motion.
32:17Propal that depresses the CNS nerve
32:20activity would be decreased with that
32:21one. Fentanyl, opioid, they said they
32:23didn't have opioid signals, right?
32:24Opioids, barbituates, those guys would
32:26depress the CNS anyways. And so that
32:28would cause the frenic nerve to go down.
32:30Halopane volatile anesthetic cause a CNS
32:33depression. They could give you other
32:34things. Tetradoxin, lidocaine, right?
32:36Those guys will block the nerve or just
32:39like kill the heart, right? The frenic
32:40nerve activity also would decrease or
32:42disappear. And then non-depolarizing
32:44blockers like tubercurine, coronium,
32:47those guys, those medications allow the
32:49nerve to still be active but the muscle
32:51is paralyzed. Non-deolarizing blockers,
32:54right? And so just thinking about this
32:55practically like your nerve is firing.
32:56Acyoline is released into the
32:58neuromuscular junction and then
33:00acetylcholine binds to the nicotinic
33:02acetylcholine receptors on the muscle
33:04end plate and this opens the ion
33:06channels and that lets the sodium go in
33:08the potassium go out and then that
33:10causes end plate deolarization.
33:11Depolarization spreads and the muscle
33:12contracts. Well, non-deolarizing
33:14blockers like tubocurine, rockaronium,
33:17bracuronium those are competitive
33:18antagonists at these nicotinic
33:20acetylcholine receptors and so the
33:21acetylcoline can't bind and so there's
33:23no deolarization and the muscle is then
33:24flaccid and paralyzed. So the nerve
33:26activity is still normal, right? The
33:28frenic nerve is still firing, but
33:29there's no muscle contraction and it's
33:30reversible with acetyloline eststerase
33:32inhibitors. So what's an example of how
33:34this is reversible? Neoigmine. So more
33:36acyloline would then flood the synapses
33:37and it'll outcompete the blocker if you
33:39give them acetyloline eststerase
33:41inhibitors. It stops the breakdown,
33:42allows more of it so they can flood and
33:44out compete this blocking stuff. All
33:46right? So yeah, cytooline is an
33:47acetylcholine receptor agonist, right?
33:49It binds and opens that channel. It
33:51causes persistent deolarization and the
33:52muscle can't repolarize so it stays
33:54paralyzed. Those are depolarizing
33:56blockers like system cooling. Maybe
33:58another way I don't want to like beat
33:59this dead horse, but like think of it
34:01like a lock and a key. Non-deolarizing
34:03that's like a fake key jams the lock and
34:05the real key can't get in, right? So the
34:07door is going to stay shut. Also known
34:09as paralysis. Depolarizing would be the
34:11real key gets stuck in the lock and it's
34:13just not going to be able to reset.
34:14There's no contraction. I don't know,
34:15maybe that's too simple of an example.
34:17Non-deolarizing, they sit right there.
34:19Antagonist blocks acetilcoline. Muscle
34:21never deolarizes. Flip paralysis. And
34:23then the deolarizing blockers, those
34:25guys act like acetylcholine. They bind
34:27that receptor a little bit too strongly,
34:29you know, and they cause big
34:30deolarization faciculations and they
34:32stay stuck. So you can't reset them. So
34:34it's also paralysis. Depolarizing,
34:36non-deolarizing. All right. In this next
34:37question here, the demographic can
34:39change. I think in the previous practice
34:40question that I made when I recorded
34:42this the first time, it was a
34:4275-year-old. Hence the photo. In our
34:44practice question now, we have a
34:4530-year-old preschool teacher presenting
34:47in the clinic in January. Two days of
34:48fever, cold, oh, fever, chills,
34:50headache, sore throat, bodyaches. Rapid
34:51antig antigen tests. confirms influenza
34:54A. She started on seltamavir. The drug
34:56most likely prevents which step in the
34:58viral life cycle. All right. So the way
34:59that the virus works, the influenza life
35:01cycle is the virus uses hemoglutin to
35:04bindic acid on the epithelial cells and
35:07that's how it gets inside and it's
35:08inside the nucleus. Then the viral RNA
35:10is replicated and now the virus buds
35:13outside of the cell membrane. But first
35:15it's got to get in with hemoglutin to
35:16bind the cylic acid on the epithelial
35:18cell. But yeah, eventually later on new
35:20viruses they butt out but they're stuck
35:21on the host cell right they're still
35:23bound to that scyic acid and so
35:25neuromminades and it cuts it and frees
35:27it. So if you give them
35:28neurommenminadase inhibitors like osel
35:30tamavir then it will block that step you
35:32know it blocks that step so they can't
35:34get out cyic acid can't be cut the
35:37infection does not spread from cell to
35:38cell and the symptoms are going to get
35:40shorter and the illness is less severe
35:41so you're blocking the release of that
35:44virus from the epithelial cells and so
35:46if we look at our question our answer is
35:47indeed going to be the cleavage of the
35:49surface scyic acid residues all right
35:51there's our explanation neurommenaday
35:53cleave scyic acid residues freeing the
35:55budding virons of oel tamavir inhibits
35:57that trapping them inside limiting the
35:59viral spread. Fusion is hemoglutin
36:01mediated transcription of RNA's negative
36:04sense into mRNA is done by the viral RNA
36:07dependent RNA pulymerase. Assembly of
36:09nucleio caspid in the cytoplasm
36:11influenza replicates it and translation
36:13of the viral pulymerase proteins.
36:14Translation in is host ribosome mediated
36:17and occurs before the butdding. All
36:18right, now this one is actually super
36:19duper simple so I don't want to harp on
36:20it too much. Broken hairs of varying
36:22lengths, triricotillamania, irregular
36:24patches of alipcia. Now this is often
36:26seen in obsessivempulsive disorders,
36:28repetitive tension relieving behavior.
36:30It's a female predominance, hence our
36:32demographic over here with their
36:33generated image as comorbid with
36:35anxiety. And basically in this
36:36condition, we have physical stress and
36:37anxiety, repetitive hair pulling,
36:39tension relief. And now how would this
36:40present in a question? Well, here we
36:41have a 12-year-old girl brought to
36:42clinic due to patchy hair loss. And so
36:44you immediately know that it's going to
36:45be D, irregular hair loss, broken hairs
36:47of different lengths, and also emotional
36:48distress, recent bullying, right? And
36:50this is an impulse control disorder.
36:52Now, why is not all these other answers?
36:53Lovium has diffused hair shedding. It's
36:55not going to be the patchy and broken.
36:56Androgenic progressive thinning, vineia
36:58capitus, scaly patches, the black dots,
37:00alpia, ariata, smooth circular patches.
37:03So really, it's just the nature of it.
37:05And that's why I wrote this when I
37:06recorded for the first time. Varying
37:07lengths. That's the huge huge deal
37:09there. Varying lengths. That's all you
37:11need to know for this one. All right,
37:12moving on to SGLT1s
37:1428. So now we're going to see this in a
37:16cute little baby. In this case, we have
37:17a two-month old girl evaluated for
37:19persistent watery diarrhea and poor
37:21weight gain. She's exclusively
37:22breastfed. Physical exam shows
37:24irritability and dry mucous membranes.
37:25Lab reveals metabolic acidosis. Stools
37:28demonstrate low pH. Oral glucose
37:30challenge is given. Serum glucose does
37:32not rise. But when you give him
37:33fructose, diarrhea improves. What
37:35mechanism is deficient? The answer is
37:37indeed C. Sodium glucose co-ansport and
37:40the interasy. So we got a little
37:41youngster, right? Breastfed. And so
37:44lactose, which is comprised of glucose,
37:46glactose and you have watery acidic
37:48diarrhea and reducing substances in the
37:50stool. Why? because the sugars are not
37:52being absorbed and so oral glucose is
37:54not changing the sugar. So the glucose
37:55is not being absorbed but the fructose
37:57is fine and the fructose pathway is
37:58intact. That tells us that glute 5 is
38:00working because that's going to be our
38:01fructose pathway. Glute 5 all good to
38:03go. So the key physiology here is that
38:05there's glucose and glactose absorption
38:06via the SGLT1 right and that is a sodium
38:10dependent transport and fructose
38:12absorption via the glute 5 is
38:13independent of sodium and so it's fine.
38:15So this is SGLT1 deficiency. you can't
38:18absorb glucose or glactose and it causes
38:20diarrhea, dehydration, reducing such
38:21sugars in the stool, but the fructose
38:22absorption totally normal. Now, another
38:24thing, SGLT1s, these are in the small
38:26intestine in the muscle. Think about it.
38:27You have four muscley limbs, right?
38:29Especially if you're lifting your
38:31calcium oxalate dumbbells. Sucrace
38:32deficiency shows after introduction of
38:34solid foods. Cool. I think this baby is
38:36cool. Like and sub if you're doing Peds.
38:38PE is the best specialty out there. You
38:40guys deserve way more money. All right.
38:41Next, our demographic has changed. It's
38:43going to be an elderly patient. In this
38:45question, we have for instance a
38:4668-year-old man with a history of hyper
38:48lipidmia and mild exertional dysmia that
38:50comes in for routine evaluation. He
38:51denies chest pain, palpitations,
38:53orthopia, physical exam, you detect a
38:54late peaking systolic murmur best heard
38:56of the right upper sternal border
38:58radiating to the crowited crowded
38:59upstroke is delayed and diminished. Echo
39:01cardiogram reveals concentric left
39:03ventricle hypertrophy and a heavily
39:05calcified aortic valve. What explains
39:07this pathology? The answer is a chronic
39:09mechanical injury from the valve
39:12function. Now, you need to be aware of
39:13something called a calcified aortic
39:14valve. In my other practice question, I
39:16had a 76-year-old male with
39:18calcification. And this is going to be
39:19seen with a systolic ejection murmur
39:21along the left sternal border. So, in
39:23elderly patients, it's the repetitive
39:24kind of micro trauma that happens with
39:26opening and closing. And that leads to
39:28aortic stenosis, which produces a
39:29crescendo day crescendo systolic
39:31ejection murmur. And it's common in
39:33patients that are greater than 65, let's
39:34say, especially have no history of
39:36rheumatic fever or congenital bicuspid
39:38valve. So this is calcific stenosis age
39:41related it's just age obstruction and
39:43left ventricle hypertrophy because of
39:45that stenosis you got a parter
39:46post-traumatic when it's fuse commissers
39:49or mital involvement prior bacteria
39:50endocarditis would be regurgitation not
39:53stenosis accelerated atherosclerosis
39:55would contribute to calcification but
39:56this is just mechanical wear deposition
39:59would be restrictive cardiammyopathy all
40:01right here's the next demographic let's
40:03say middle-aged man middle-aged woman
40:05not too important here 41-year-old woman
40:07here presenting to emergency department
40:08with a two-day history of persistent
40:10right shoulder and upper abdominal pain.
40:12Recently lost 30 lbs over 4 months
40:14through a low carb, high protein crash
40:15diet. She's got some nausea, low-grade
40:17fever, 101.1 KLRC. Just kidding.
40:21Temperature on exam. She winces and
40:23abruptly stops inspiration during
40:25palpation of the right upper quadrant.
40:27Labs reveal all this good stuff. What's
40:29the diagnosis? All right. So, the big
40:31things that I see in this question, and
40:32I've written some notes over here
40:34before, is we have some rapid weight
40:36loss, right? So here we have losing a
40:38lot of pounds in a short amount of time.
40:39So that's like a risk of a gallstone T
40:41ratio, right upper quadrant tenderness.
40:43That's what we're seeing here. There's
40:44no blood in the stool, right? So that
40:46means it's not like a GI bleed. But that
40:47rapid weight loss increases the
40:49cholesterol stimulation to the bile. So
40:50so like you get more of that cholesterol
40:52and then you get obstructed cystic ducts
40:54and that causes an inflamed gallbladder
40:56wall leading to acute choleiccyitis. So
40:59that's the right upper quadrip,
41:00luccoytosis, biliary lab stuff. And
41:02there are a couple of answers that you
41:03should always be thinking about with
41:05these types of questions. One of them is
41:07acute pancreatitis and that would have
41:08elevated amalayise and lipase levels.
41:11It's super important to know those two
41:13lab values for acute pancreatitis. Small
41:15bowel obstruction there's no signs of
41:17obstruction. That'd be like a prior
41:18surgery or distension. Hepatitis A would
41:20be recent travel jaundice malaise all
41:21that stuff. And gastritis is NSAID use
41:23alcohol. Nawing epigastric pain would be
41:25gastritis. They could also say things
41:26like try to get you on gird. Gird would
41:28be seen with a burning chest epigastric
41:30pain not right upper quadrant pain.
41:32Burning epigastric gird could a proton
41:35pump inhibitor. You could also be seeing
41:36or on test they might ask you about like
41:38a fatty liver and that's usually just
41:40completely silent or even chronic.
41:42There's no lucostosis or anything like
41:43that in the fatty liver or a peptic
41:45ulcer they could get you on and that's
41:46pain GI bleeds a cold blood and that's
41:48not going to be seen in this patient
41:50right the peptic ulcer would maybe cause
41:51some bleeding so fat female fertile 40
41:54and if you wanted to you could even add
41:55fat weight loss right that's an extra
41:57extra risk as well. All right. Next, we
41:59have a 64-year-old woman with advanced
42:00multiple scerosis, admitted to long-term
42:02care facility, recurrent
42:02hospitalizations of a urinary tract
42:04infections, wheelchair bound, has
42:06difficulty moving her lower extremities,
42:08physical exam, she's alert, minimally
42:09interactive, BMI is at 19. What's most
42:11effective in preventing skin breakdown?
42:13The things to look out for on test day
42:14for this condition is going to be
42:15paraplegia. So, somebody is like
42:17immobile usually is how they'll ask
42:19this. They're admitted with a urinary
42:21tract infection and you're trying to
42:22prevent the skin breakdown. So, you
42:24should think of decuitous ulcers, right?
42:26Does skin breakdown from prolonged
42:27pressure on bony sites? Where are your
42:29bony sites? Well, it's like your elbows,
42:31right? Your scalp, your heel, your
42:33sacrum. So, the mechanism is increased
42:35pressure. This is really interesting.
42:36Increased pressure causes a decreased
42:38blood flow that causes eskeeia that
42:39causes tissue death that causes ulcers.
42:41This question is really actually kind of
42:42a good one because you're trying to
42:43protect the ulcers. You don't want the
42:45ulcers to happen, but you have to
42:46recognize that this person is a
42:47long-term care facility, wheelchair
42:49bound. They're sitting on their butt all
42:51day, right? And and they have a lot of
42:53pressure points at the bony sites. And
42:55so that bony pressure causes less blood
42:57flow causes that eskeeia and that causes
42:59tissue death. So really a really good
43:01question here and you need scheduled
43:02turning and repositioning. So the answer
43:03C, you got to reposition. Just because
43:05of the low BMI does not mean high
43:07protein mal nutrition. You should
43:09instead think about what the questions
43:10exactly asking. Topical antibiotics that
43:13would treat the infection not the
43:14eskeemia. Barrier cream helps with
43:16moisture but not preventing necrosis
43:18caused by eskeeia. Antiseptic washes nah
43:21that would not prevent eskeemic
43:22cultures. And now this is actually
43:23really slept on. Like not a lot of
43:24people, no pun intended, I guess. But
43:26yeah, it's about over 2.5 million
43:29patients in the US develop pressure
43:31ulcers every single year. And many of
43:32them are entirely preventable, right? So
43:34if you guys are rounding on a physician
43:36someday, you should be like, "Hey, have
43:37you moved from that position in a
43:38while?" Like, let's move. Yeah. Let's
43:39get the blood flowing. But maybe some
43:41other things they might try to get you
43:42on would be like arterial blood flow.
43:44And that' be for like vascular disease
43:45ulcers, not pressure ones. They could
43:47also get you on nutritional stuff,
43:48right? That'll help the healing, but
43:49it's not going to stop the ulcers from
43:50forming. They could also get you on like
43:52bacterial skin flora stuff, right?
43:54That's bacteria that infects the ulcers
43:55after they form, but it's not the actual
43:56cause of it or like venus stenosis. And
43:59those are just different types of
44:00ulcers. So, they're going to test you on
44:01different ulcer types. Usually known
44:02that it's pressure ulcer. All right,
44:04going to hide the answer here and move
44:05on to 32. 64 year old man, 15-year-old
44:08history. So, different demographics
44:10here. Female could be as well around the
44:12same age, but we got poorly controlled
44:14type 2 diabetes, chronic fatigue, bone
44:17aches. Look at that phosphate. It's
44:18high. Should be 2 to fourish. So
44:20phosphate then maybe there's a kidney.
44:22Oh yeah, look at that [ __ ] Holy cow.
44:24Big old kidney problem. Bun. All right.
44:25So what's the abnormality thing going on
44:27here? Well, definitely we're having
44:29trouble because we have kidney problems,
44:31right? It seems like there's kidney
44:32problem that's causing secondary
44:33hyperarathyroidism. And so our answer is
44:35going to be C. Let's talk about this
44:37though. So in the other question I
44:38recorded, I had a 58-year-old female. In
44:40this question, we have a 64 year old
44:42man. So the kidneys make vitamin D. And
44:44that's kind of crazy, right? Because it
44:46makes you think of like the calcium of
44:47it all. And that that it's helpful
44:49because in renal failure you have
44:50decreased vitamin D and decreased
44:52calcium absorption. So calcitrial being
44:54vitamin D is helpful. But yeah, it helps
44:56the gut absorb the calcium. That's the
44:57whole role of the vitamin D. That's one
44:59of the reasons why the kidney makes it.
45:00Phosphate is like the trash, you know,
45:02get it out of there. So in renal
45:03failure, you have decreased vitamin D.
45:04So that causes hypocalcemia because you
45:06don't have that calcotriol. So you can't
45:08absorb the calcium. And also the
45:09phosphate secretion decreases. You have
45:11hyper phosphatemia, more of it. You're
45:12like, "Oh my gosh, too much of it, can't
45:13get rid of it." hypocalcemia,
45:15hyperosphemia that stimulates the
45:16parathyroid gland causing secondary
45:18hyperarathyroidism. And so on the labs
45:20you'll see low calcium, high phosphates,
45:22high PTH. And now the the question that
45:24I usually get and I'll allow you guys to
45:26kind of see my beautiful face and my
45:27room. Check it out. By the way, I'm
45:29doing this because you guys told me that
45:31you'd prefer this over the green screen.
45:33Let me know if that's still the case cuz
45:34the green screen is kind of fun, you
45:35know. But anyways, you might be
45:37wondering, okay, why does the PTH go up
45:39in chronic kidney disease? The kidneys
45:41normally help the calcium and the
45:42phosphate be balanced, right? So you
45:45convert the vitamin D calcitrial. We
45:46talked about this. Well, in chronic
45:47kidney disease, we obviously don't have
45:49calcitrial. So the gut does not absorb
45:50as much calcium and so there's
45:51hypocalcemia and there's no phosphate
45:53excretion. And what's kind of even worse
45:55is that this extra phosphate that's just
45:57like in our body is going to bind the
45:59free calcium and that then lowers the
46:02ionized calcium even more. And then the
46:04parathyroids are like, "Oh my freaking
46:05gosh, we have low calcium here and
46:07that's our one job, right? to keep the
46:09calcium normal and so we need to secrete
46:11more parathyroid hormone and so that's
46:12secondary not caused by like some tumor
46:15or something there it's secondary to the
46:16other issue of the kidneys secondary
46:18hyperarathyroidism PTH goes up in
46:20response to chronic low calcium and high
46:22phosphate so PTH tries to fix things
46:24it's like let's increase the bone
46:25reabsorption let's let's like stimulate
46:26those osteoclass let's release that
46:28calcium and that phosphate and let's
46:29stimulate the kidney let's also
46:31stimulate the kidney this is PTH
46:32speaking so that we can make calcitrial
46:35but then the kidneys are damaged right
46:36so that's not going to work very well
46:38and you increase the calcium
46:39reabsorption in the kidney and again
46:40this is limited in chronic kidney
46:42disease and so that PTH is just going to
46:43be rising and rising but the calcium is
46:45never fully going to normalize and so
46:47you have persistent high barathyroid
46:49hormone all right so it's low calcium
46:51high phosphate high PTH hopefully I
46:54explained that well if you guys think
46:55this is helpful please like and
46:56subscribe takes a long time to make
46:57these videos double time if you forget
46:59and do this accidentally but yes it's on
47:01it's blue okay good all right guys and
47:03gals there was a study that I read
47:05recently that said women physicians are
47:07like just holistically better than male
47:08physicians. They have like better
47:09outcomes for patients. And I was like,
47:11that makes sense. Anyways, we are on
47:13question 33. I'm going to try to speed
47:14through these, but our demographic for
47:16this question is going to be somebody
47:17who's like pretty fit. Reminds me of
47:18that Modern Family episode. I want to
47:20dance to the ballet. 29-year-old ballet
47:22dancer presents with chronic right knee
47:23pain after high impact performances.
47:25Imaging shows thinning of the articular
47:28cartilage, but nobody involvement.
47:29Biopsy of the affected tissue reveals
47:30reduced hydration and compression
47:31tolerance. Which biochemical feature of
47:33normal cartilage molecule explains the
47:34ability of the to maintain the high
47:36water content in physiological
47:38conditions? Okay. Now on the surface
47:39this this can be pretty tough but like
47:40what this question is asking is
47:42essentially why does cartilage via
47:44chondroitin sulfate swell and occupy
47:46more space in water than it does in a
47:49dry solid. And and so what we need to
47:50know is that there's this thing called
47:52chondroitin sulfate. I'm going to zoom
47:53in. I've taken notes in this before.
47:55This is a glycosaminoglycand or g a as
47:58you may have seen it in your med school
47:59classes. Gags have tons of negative
48:02charges. In fact, anytime you guys see,
48:04this is a little tip. Anytime you see
48:05sulfate, just click negative charge.
48:07It's going to be the answer. I swear
48:08like every single time. I've seen so
48:09many times where sulfate is just
48:11negatively charged is the answer. And
48:13yeah, negativity, right? It attracts
48:14lots of water, the hydration shell,
48:16right? So, and so you have the
48:17negatively charged that repels each
48:19other and the molecules spread out and
48:20the negativity that attracts a lot of
48:22water. And so, that together makes a
48:23gel-like space occupying shock absorbing
48:26structure that's good for cartilage. And
48:28so our answer is high density sulfate
48:29and caroxilate groups. Let's explain
48:30this a little better. Condroitin sulfate
48:32is rich in sulfate and caroxilate. So
48:34it's highly negatively charged attracts
48:36water through these electroic
48:38interactions leading to repulsion
48:39between chains. Hydrated mixture allows
48:41cartilage to absorb mechanical stress.
48:43Hyaluronic acid does not explain
48:44hydration. Lizal degradation would be a
48:47storage disorder not water retention.
48:48Coalent linkage it's for anchoring not
48:50swelling and n glyosillation would be
48:53protein glycosillation not the hydration
48:55behavior. All right. So maybe there's a
48:56way that you can remember this by saying
48:58gag on water, right? Gags gag on water.
49:00Glycosaminoglycans have negative charges
49:03and so they soak up the water and that
49:05gel cushion can form. I want to make
49:07this super duper simple. I worry that I
49:08over complicated this one. Maybe I
49:10didn't. I don't know. But basically
49:11chondroitin sulfate has tons of
49:12negatively charged molecules. Negative
49:15repels negative that causes these
49:16molecules to spread out. Negative
49:17attracts water. It swells. Becomes
49:19gel-like. That's the answer. That's it.
49:20They're going to try to be like, "Oh,
49:22but collagen. Oh, you've seen collagen
49:24before. Or what what if I said collagen
49:25binding? Don't you have to choose that
49:26because you know what collagen is? I
49:28don't know, maybe I'm projecting, but
49:29that's how I feel sometimes. Structural
49:31support, right? Anytime you see
49:32collagen, think structure, right? Not
49:34swelling. How about coalent bond with
49:36core proteins, right? That's how
49:37proteoglycans are built. That's not why
49:39they expand, right? Coalent bonds do not
49:41tell you necessarily about the
49:42expansion. And they could try to get you
49:43with like the end stuff. They'll say,
49:45"Oh, what about the n-lin
49:46oligosaccharides?" Well, that's a
49:48glyoprotein modification. And it's just
49:50going to be unrelated. So, gags gag on
49:51water. They have negatively charged.
49:53They soak up the water and they cause
49:54that gel cushion to form. Hopefully that
49:56makes some sense. All right, next we
49:57have a 27-year-old man collapsing while
50:00hiking in Arizona. Been exposed to high
50:01heat for hours. Didn't drink water. His
50:03vital stoic cardia hypotension. By the
50:05way, always drink water. Check this out.
50:07It's so good. So good for your kidneys.
50:09This is how much you need to drink in a
50:10day. It's probably more than you
50:11thought, but I digress. Anyways, this
50:13could be any any demographic. It could
50:14be an older woman, could be older man,
50:16could be whatever. So, I'm just putting
50:17that question demographic up there. But
50:18yeah, the serum is 150. Dehydrated state
50:21is what we're talking about. And what's
50:23most critical in helping to conserve the
50:24water? It is the ura transport into the
50:26meillary interstitium from the
50:27collecting duct. So the answer is C. And
50:30a way that you could see this is like
50:31okay a a man or a woman is running a
50:33marathon. They get dehydrated. And that
50:35dehydration means you got increased
50:38plasma. Osmolality is the concentration
50:39of a solution as expressed by the total
50:41number of solute particles per kilogram.
50:43Okay? So you got a lot of solute. And
50:44the brain senses this. The brain's like,
50:46"Oh my gosh, we got a lot of solute.
50:47Let's release the hounds. Let's release
50:49ADH." Like Mr. Burns. ADH is a fancy
50:52little thing. It's also known as a
50:53vasopressin. All right. Now, the main
50:55job of ADH is to put the aquaporins in
50:57the collecting duct. Chunk, chunk,
50:58chunk, chunk. Just puts them there,
51:00right? Hey guys, let's upregulate the
51:01aquaporins. It also has a side job. And
51:03that side job, it's side hustle is it
51:06increases the ura reabsorption through
51:07the medularary collecting duct. All
51:09right. So, we're increasing that ura as
51:11well, that absorption. And the ura
51:12really helps the vidola stay salty,
51:14right? The high osotic gradient. I took
51:16a class on like nefrology at Harvard
51:18from one of like the most foremost
51:20experts on the kidneys and I swear every
51:22five minutes he'd say we need to
51:23preserve the osmotic gradient of the
51:25kidney. So yeah, it's super important
51:27that we just like preserve that osmotic
51:28gradient. And here's our explanation.
51:30Dehydration response by increasing ADH
51:32not only increases aquaporn insertion
51:33for water absorption but also increases
51:34ura transport medularary interition. The
51:37ura makes a gradient drawing more water
51:39out of the collecting ducts and
51:40concentrating them. So it's all about
51:41that gradient, right? ADH is the main
51:43hormone that saves water. It adds water
51:45channels to the duct and it pulls ura
51:47back into the duct making the medola
51:49extra salty and that helps it suck out
51:52even more water. All right, so ADH adds
51:54water adds ura. That's how I want you to
51:55think of ADH and we're done with that
51:57question at least. All right, we're
51:58going to have to go quickly. Macroitic
52:00anemia, alcoholism, seizure,
52:01macroytosis, hyper segmented neutrfils,
52:03low retic count, ineffective
52:05erthropoesis is what that means. So you
52:07see macroitic anemia, low folate intake,
52:09rapid depletion, B12. And then the other
52:11thing to know about B12 is that it has
52:13an increase in both, right? Vitamin B12
52:15deficiency takes years to develop and
52:17you can see both increase in homoyine
52:18and MMA. All right, so for this question
52:2035, the big things to look out for are
52:22macroitic anemia, a retic count is low.
52:24That means we're not making red blood
52:25cells very well. And there's also
52:26alcoholism, malnutrition, that's a
52:28vitamin deficiency, and the stores of
52:30folate are going to run out super
52:31quickly, but then the vitamin B12
52:32deficiency takes years to develop.
52:34Right? So here we have a 44-y old woman
52:36brought in by a roommate, confused,
52:37tremulinous, history of alcohol use
52:40disorder. The answer is going to be a
52:41folic acid deficiency. Here are the
52:43answers and the explanations. They're
52:44going to try to trap you various ways.
52:45They might say lead toxicity that's
52:47microit. Might say iron deficiency
52:49that's also microitic. Betathalismia
52:50that's also microitic. Thamine
52:52deficiency. They could see like warnicks
52:54and sephylopathy, but that's not going
52:55to be a cause of anemia, right? So they
52:57could do a whole bunch of things.
52:58Vitamin B12 is another one to look out
53:00for, but a B12 deficiency takes years to
53:03develop and folate runs out more
53:04quickly. Alcoholism and malnutrition
53:05tells you it's probably like a vitamin
53:07deficiency. You might be wondering okay
53:08like folic acid deficiency vitamin B12
53:10deficiency which one is like alcohol is
53:12more related with folate deficiency it's
53:13much more common much faster and for B12
53:16deficiency the causes are usually
53:17pernicious anemia gastric bypass Crohn's
53:19disease vegan diet so the stores are a
53:20lot a lot less for folate so it runs out
53:22in weeks to months all right next we're
53:24going to be talking about a 27-year-old
53:26kindergarten teacher presents with
53:27spontaneous gum bleeding widespread beta
53:29coverage from a cold two weeks ago here
53:31are her labs what's the underlying
53:32mechanism it's auto antibody mediated
53:34platelet destruction so you know it's
53:36might like a young woman here who's a
53:38kindergarten teacher. You can see our
53:40photo. Easy bruising, viral illness a
53:42month ago, thrombocytoenia, bone marrow
53:44smears, right? Which are like
53:45meggaarioytes. Viral infection causes
53:48the way that that this typically works.
53:50This is by the way ITP is like a ruling
53:51out diagnosis, but you have a viral
53:53infection and then the immune system
53:55gets all activated and then you start to
53:56make antibodies against the platelets
53:58and that is anti-GP2B3A
54:01and so the platelets get destroyed in
54:03the spleen. spleen the bone marrow is
54:04still healthy so it just makes more and
54:06that's why you have meggaariotes it's
54:08like a good positive response that
54:09you're trying to do you're trying to
54:11build meario so you can respond to the
54:13lost platelets and this is immune
54:15thrombocyopedia and papura it's an
54:16immune problem all right they could try
54:18to trick you in various ways here are
54:20some trap answers bone marrow failure
54:22that would have hypocellular marrow B19
54:24is a plastic splenex sequestration
54:26splomegaly but here actually they didn't
54:27mention spleengaly interestingly enough
54:29but yeah the sequestration would not
54:30necessarily come from a viral illness
54:32dic C elevated PT and PTT and and just
54:35briefly on the spleen you might ask okay
54:37so if platelets are being destroyed in
54:38the spleen then why would not the spleen
54:41like be the answer or in the answer and
54:42so like this question is going to ask or
54:44question you might see is what's the
54:45most likely cause of the thrombocyopenia
54:47well the cause is immune mediated
54:49destruction of the platelets and the
54:50spleen is the place where destruction
54:51happens but the mechanism is still auto
54:53body antibbody mediated pl antibbody
54:56mediated platelets optinization and it's
54:58the splenic macrofasages that clear them
55:00and so if it said like splenic
55:01sequestration as the cancer like big
55:03spleens from sterosis or portal
55:04hypertension. Well, that's kind of a
55:06different mechanism, right? So, in
55:07sequestration, the spleen traps the
55:09platelets mechanically. In ITP, it's the
55:11auto antibodies that target the
55:12platelets and it just happens to be the
55:13spleen that recognizes and destroys
55:14them. Hopefully, that makes sense. Think
55:15of it this way. Big spleen
55:17thrombocytoenia by sequestration. Normal
55:20spleen, recent infection, meggaario,
55:22that's probably ITP.
55:24I know that can be confusing at times,
55:26so I just wanted to kind of point that
55:27out. Oh, I should probably have written
55:28that down. Big spleen, thrombocyopenia,
55:30normal spleen, recent infection with
55:32that autoimmune activation and the
55:35presence of meggaarioytes and low tells
55:38you got ITP, right? Peripheral immune
55:40destruction. All right. In our next
55:41question, we have a 59-year-old man
55:43could also be a woman. The 40 pack
55:44presents with new onset fatigue,
55:45elevated blood pressure, and difficulty
55:46rising from chairs. He denies pain or
55:48sensory changes, physical exam, shows
55:49moonface, e central obesity, and
55:51decreased muscle bulk in the thighs,
55:53fasting glucose of 178. T reveals
55:55central pulmonary mass encasing the
55:57right main broncus main bronchus which
56:00hormone is most likely responsible for
56:01the muscle weakness oh and biopsy shows
56:03small dark blue cells of chromog and a
56:05well we had moon faces and central
56:06obesity and that tells us is cushing
56:08syndrome and that's usually hypoglycemia
56:09you see like you know proximal muscle
56:11weak proximal proximal muscle weakness
56:14you know trouble standing up but this is
56:16kind of a tricky one right because and
56:17also this is important like I kind of
56:19lit up you saw whenever I saw central
56:21pulmonary mass and that's because I I've
56:24made a couple videos on this and the
56:25last recording I did that was two hours
56:26long. I went through and I explained all
56:28of the lung diseases. I should like
56:30release the muted version of that
56:31because I get so excited when I talk
56:32about this because there's a really
56:33simple way of not missing questions like
56:35this in the future. But here I know that
56:37this is small cell or it's going to be
56:38squamous cell if it's central. And so
56:41small cell carcinoma can secrete ectopic
56:43hormones. So that could kind of explain,
56:44you know, the muscle weakness, the
56:45hypoglycemia, the Cushing syndrome
56:46stuff. And you can have a tumor that
56:48secretes ACT and that overstimulates the
56:49adrenal cortex and that causes the
56:51increased cortisol explaining the
56:52Cushing. Isn't this crazy? like medicine
56:54is kind of crazy sometimes but here the
56:56answer is adrenocortic adrenoortropic
56:59hormone and it's because of that ectopic
57:01act from the small cell and here I think
57:03it's like super important to actually
57:05look at these answer choices vasopressin
57:07inappropriate ADH would cause
57:08hyponetreia not hypoglycemia so it ain't
57:11vasopressin calcetonin medillary thyroid
57:13carcinoma inhibits bone reabsorption not
57:15with cushing this one PTHP that's
57:18hypoglycemia malignancy that'd be
57:20squamus it causes calcia not
57:22hypercortisol so that keeps you into the
57:24different type of cancer IGF-1
57:26acromegaly. So yeah, there are some
57:28tumors that make you diabetic, weak,
57:29puffy spa, puffyfaced and it doesn't
57:32even touch your pancreas or your
57:33pituitary gland. It's the paranoplastic
57:35syndromes of the small lung cell cancer
57:37cell you should think of. PTHRP
57:39parathyroid hormone related protein and
57:40that one causes an increase of calcium.
57:42All right, looks like I did graffiti all
57:43over this question in my last video.
57:45This one, aspirin makes it worse. Let's
57:46talk about when aspirin exacerbates
57:48things. Well, there's something called
57:49aspirin exacerbated respiratory disease.
57:51It's associated with chronic rhinositis
57:53with nasal polyps. Here we have a 29
57:58year old woman, but it could be anybody
57:59and especially somebody young like it
58:01could be like a 15 year old girl or boy
58:04for instance that's kind of like this
58:06demographic and they have onset asthma
58:08presents with shortness of breath and
58:09wheezing 30 minutes after taking an
58:11overthec counter. So it's aspirin
58:12exacerbated and you have to know the
58:14mechanism of aspirin is cycle oxygenase.
58:15All right. So they have non- selective
58:17irreversible inhibi inhibition of cox 1
58:19and two phospholipase A2 steroids
58:21inhibit it five lip oxygenase dilutin
58:23blocks it lucatrine downstream and
58:25prostate is downstream as well so yeah
58:27aspirin can make asthma worse so it's
58:29important to remember gluccocorticoids
58:30can block phospholipase A2 but that's
58:32like way upstream and then aspirin and
58:34NSAIDs block cox and then zilutin blocks
58:37five lipooxygenase and montalucas blocks
58:39the lucatine receptors all right this
58:41next one's pretty easy it's just an
58:42opioid overdose pinpoint peoples is what
58:44you need to know low low respiratory
58:45rate there's to try it for opioid
58:47intoxication. 23-y old man unconscious
58:49at a bus station. Small bag of crushed
58:50pills is found. Withdrawals to pain does
58:52not open the eyes. Horse speak.
58:53Basically, he's got a CNS depression.
58:55Brea predypnia. So, his respiratory rate
58:57is like super low. That's opioids. And
58:59so, the answer is D. Pulse is decreased,
59:01respiration is decreased, pupils are
59:03constricted. Super simple. The mental
59:04status you have like a sleepy comese
59:06patient. The breathing is depressed.
59:07It's slow, shallow, heart rate is
59:09radicardic. And hypotension, the pupils
59:11are pinpoint. That's opioid overdose. I
59:13feel like a lot of people know this one.
59:15So, those are the notes that I took on
59:16the last one. And by the way, you give
59:17him an inlloxxone for that. That's the
59:19antidote. All right. So, here we have a
59:2029-year-old woman, 34 weeks gestation,
59:23presents to her primary care physician
59:25with a three-day history of fever,
59:26myalgia, loose stool. She nice cough,
59:28dysphoria, and rash. She has no pets.
59:30She ate cheese, fruit platters, smoked
59:31salmon, febrile, luccoytosis, catalase
59:34positive, grandpositive with tumbling
59:35motility. What led to this? It's the
59:37eating of the soft cheese. Right. This
59:38is lististeria. So, the blood culture
59:40shows small grandpositive rod. And
59:42here's just a matter of memorizing all
59:43these rods, which is so silly because we
59:45can just look them up on the internet.
59:46But don't get too cynical yet. Things
59:47will change eventually. Fever, nausea,
59:49headache, that's what you should look
59:49for in this one. Catalace positive,
59:51tumbling motility. What else about
59:52lististeria? It grows in cold
59:53temperatures. So it survives in
59:54unpasteurized dairy, their soft cheeses,
59:56cold deli meats, all that stuff. And the
59:58high-risisk patients are going to be
1:00:00pregnant women. I would say nine times
1:00:01out of 10, that's going to be your
1:00:02demographic. Also like you know,
1:00:03neonates, elderly, immuno compromised,
1:00:05but for some reason on step they just
1:00:06love asking about the pregnant woman.
1:00:08And so in pregnancy you have like mild
1:00:10flu illness in the mom but it can cause
1:00:12choreo amniitis, fetal demise, neonatal
1:00:16sepsis, menitis, all that stuff. Okay,
1:00:18here are the explanations. Raw poultry,
1:00:19camplebacttor risk, smoked salmon, less
1:00:21likely for lististeria, diarrhea,
1:00:23shagella, but they're the blood you'd
1:00:25see tons of shagella farm animals ecoli
1:00:27associated. So lististeria likes lunch
1:00:29meat. That's how you remember it. This
1:00:30next one is one of my favorites for some
1:00:31reason. Water syndrome. The pathophysiz
1:00:33you have a vipratic islet cell tumor. VP
1:00:36binds intestinal epithelial receptors,
1:00:37increases the camp, chloride, sodium and
1:00:39water secretion. You get just tons of
1:00:40watery diarrhea and it inhibits gastric
1:00:42acid. You treat it with somatin labs.
1:00:44Low potassium, low chloride, high by
1:00:47carb, increased VIP. Octriotide inhibits
1:00:50VIP secretion. So here we have a
1:00:5246-year-old woman could also be a dude
1:00:54as in her demographic there. Progressive
1:00:56fatigue, lightheadedness, and six days
1:00:58persistent profuse watery diarrhea is
1:00:59what we're thinking of. And so you give
1:01:01satastatin analog the trap answers
1:01:03pancreatic enzyme. That'd be for
1:01:05steadorhea, nonatory diarrhea. Leperide
1:01:08is an opioid analog. Different
1:01:09mechanism. Insulin infusion for
1:01:11hypoglycemia or DKA. H2 receptor
1:01:14antagonism is for acid suppression. So
1:01:16yeah, a rare pancreatic tumor is what
1:01:17this person's got. You can actually
1:01:19cause up to like three liters of watery
1:01:21diarrhea. So it's just like profound
1:01:22watery diarrhea. So you also get
1:01:24hypotension, hypocalemia. The stool
1:01:26output is like 3.5 liters a day. It's
1:01:28associated with men one syndrome. arises
1:01:30from the pancreatic tail octriotide
1:01:32flush face watery diarrhea
1:01:34hypocchloryria or achlory and
1:01:36hypocalemia it's a vipoma pancreatic
1:01:40neuroendocrine tumor secretreting the
1:01:42vasoactive intestinal peptide all right
1:01:44next what's the swelling that enlarges
1:01:46with crying indirect it's a
1:01:47communicating hernia softucible mass in
1:01:50the groin lateral to the inferior
1:01:52vessels this is going to be seen in kids
1:01:54I remember that because ki d kid I
1:01:57indirect processes vaginal Alice fails
1:01:59to obliterate leaving a pathway and then
1:02:02the abdominal contents herniate in there
1:02:03and it's indirect. So it could be a
1:02:05super youngster like this cute little
1:02:06baby on the top. And so here's our
1:02:08question. Two-month old male evaluated
1:02:09for swelling of his left groin. The
1:02:10parents noticed during diaper changes.
1:02:12Swelling enlarges when the child cries
1:02:13and disappears when he's calm. On
1:02:15examination, a soft non-tender reducible
1:02:17bulge is not in the left groin. What's
1:02:18going on? It's a lateral to the inferior
1:02:20and superior to the inguinal ligament.
1:02:21Indirect. What about all these other
1:02:23answer choices? Well, we kind of got to
1:02:24know them. Inferior to the inguinal is
1:02:26femoral. That's in women. For step one,
1:02:28just think it's in women. Just they're
1:02:29not going to test you on harder than
1:02:30that. Superior to ligament, direct
1:02:32inguinal in adults, medial to the
1:02:34vessels, not going to see anything
1:02:36there, especially not above the
1:02:37transversal fascia. Femeral canal,
1:02:40lateral, again, femoral hernia
1:02:41territory. So, we got a young kiddo and
1:02:43a groin bulge that worsens whenever they
1:02:45cry and it goes away whenever they're
1:02:46resting. Indirect inguinal hernia every
1:02:48single time. It's the failure of the
1:02:49processes vaginalis to close. And the
1:02:51anatomy is the indirect inguinal hernia.
1:02:53So it will pass through the deep
1:02:54inguinal ring into that canal in the
1:02:57superficial ring. So it can even reach
1:02:58the scrotum and it's lateral to the
1:03:01inferior epigastric. Remember MDs lie
1:03:03medial direct lateral indirect lateral
1:03:05to the inferior and it's superior to the
1:03:07inguinal ligament. And so direct
1:03:09inguinal hernia is medial to the
1:03:11inferior epigastric through this hes
1:03:12triangle. And the femoral hernia is
1:03:14inferior to the inguinal ligament.
1:03:17Right? So it's all about that inguinal
1:03:18ligament. Right? If it's medial to the
1:03:20inferior epigastric, then it is a direct
1:03:23inguinal hernia. If it is lateral to the
1:03:25inferior epigastric, then it is an
1:03:27indirect hernia. Remember, IMD's lie.
1:03:30Lateral, indirect, medial, direct. Older
1:03:32people, kids. Done. All right, let's
1:03:34talk about par, the party. For those of
1:03:36you who have gone to parties, I've never
1:03:38gone to a party before, but I hear
1:03:39they're fun. We have a 54y old woman.
1:03:41Could be a man as well, so check our
1:03:42demographic image here. Could be either.
1:03:44six-year history of type two diabetes
1:03:46follow visit blood glucose remains
1:03:48elevated despite maximum doses of
1:03:49metformin and we're now going to try a
1:03:50medication that imp improves insulin
1:03:52sensitivity by binding to a nuclear
1:03:53receptor one month later we have mild
1:03:55weight gain which drug the mechanism
1:03:57action peroxazone proliferator activated
1:04:00receptor gamma I have a video on all
1:04:01these drugs but here we got the way that
1:04:03you'll see this on test day is
1:04:04somebody's going to have type two
1:04:05diabetes they're going to be on like
1:04:07glyide or surfonhea and metformin and
1:04:10they're still not going to go anywhere
1:04:11with it the next step after you've tried
1:04:13a glyide like surfora or a metformin,
1:04:15you're next going to go to poglitazone.
1:04:17The mechanism there is very clear. It's
1:04:19you glitter, you need glitter to go to
1:04:20the party. That's how I remember it. So
1:04:22glitzone to go to the party. Okay? So it
1:04:23binds the par it binds the par gamma and
1:04:27I I like to say the gamma is like a y
1:04:29glitter zone glitter to the paroxazone
1:04:32proliferator activated receptor gamma.
1:04:34That's what it stands for. So the par
1:04:36gamma is a nuclear transcription factor
1:04:38that's found in the atapose muscle liver
1:04:40and the activation increases the gene
1:04:42expression for the insulin sensitivity.
1:04:43And so you have better glucose uptake by
1:04:45the muscle and the fat and then you have
1:04:46decreased apatlucanogenesis. It's not a
1:04:48glp1 agonist like lel glutide that
1:04:51increases insulin secretion and
1:04:52decreases glucagon. So you remember
1:04:54glitazone or you can remember p for par
1:04:56and p for poglitazone but yeah either
1:04:58way that's for peripheral sensitivity.
1:04:59Now let's look at these explanations.
1:05:01activates PPR Y ademma weight gain. AMPK
1:05:03would be metformin. DPPP4 inhibition
1:05:06citagglytin SGLT2 flows in the liver
1:05:09promotes glucosera. Potassium channel
1:05:11inhibition sane reas causing insulin
1:05:13secretion. Cool beans. All right. Now,
1:05:15this is about where I was when I lost
1:05:16the recording last time, but there's a
1:05:18really easy hack for this question.
1:05:20Basically, if you see an
1:05:21African-American individual or somebody
1:05:23from the southeast kind of Asian
1:05:25descent, it's like maybe a sailor. They
1:05:27get lots of sun, but they don't sunburn
1:05:28is the point. So dark skin has like
1:05:30protective melanin, right? And so
1:05:32basically they would be at melanoma risk
1:05:34and in darker skin the UV related
1:05:36melanomas are like less common, right?
1:05:38Because melanin is protective. And so
1:05:39anytime you see that kind of scenario
1:05:42forming on your question stem,
1:05:44immediately lock in acry lintigenous
1:05:46melanoma. That's a darker linear streak
1:05:49on the nail beds in patients with darker
1:05:50skin. And that's how they're going to
1:05:51test on test day. I know it's just it is
1:05:53what it is. The classic sites are going
1:05:55to be the palms, the soles, and the
1:05:56nails. And it's most common in
1:05:57African-American and Asian patients.
1:05:59That's just how it is. That's how they
1:06:00test it. And like other answer choices
1:06:03like the the chest, forehead, all that
1:06:04stuff. Those are like sites for UV
1:06:06related melanomas and superficial
1:06:08spreading and non lintigo malignant. But
1:06:10that's less common in darker skin. So
1:06:11the darker skin really lends you more
1:06:13toward the acmelanoma. All right. Now,
1:06:14this one is wild because almost as soon
1:06:16as I recorded this, I went out and
1:06:18bought this mouse so I can make better
1:06:20videos for you guys on Facebook
1:06:21Marketplace. And I met somebody who had
1:06:23this condition. She literally told me
1:06:25that she had acute inflammatory
1:06:26demiinating poly ridiculopathy. And I
1:06:28was like, that is a mouthful. And also,
1:06:30I've never actually that was the first
1:06:32time I'd seen a patient with that. But
1:06:34anyways, 35-year-old woman, 4 days
1:06:36progressive weakness, difficulty
1:06:37climbing, tingling in her toes, episode
1:06:40diarrhea after eating undercooked
1:06:41poultry, lumbar puncture reveals
1:06:42elevated protein with white blood cell
1:06:44count, answers, antibbody mediated
1:06:46demolination of the peripheral nerves.
1:06:47So yeah, this is kind of pointing out
1:06:49gam but like specifically the acute
1:06:51inflammatory deilating polymoropathy and
1:06:53so it's post-infectious autoimmune cross
1:06:56reactions. The antibodies attack the
1:06:57myelin of the peripheral nerve roots and
1:06:59demalination slows the conduction time.
1:07:01So polio anterior horn is polomiitis not
1:07:04ascending asymmetric spinal atrophy of
1:07:06the muscles axonal cortical spinal loss
1:07:09and ALS postnaptic acoline is mythenia
1:07:12gravis or what's interesting is that gon
1:07:14beret is the most common cause of acute
1:07:16flaccid paralysis in the United States
1:07:17today it's not polio it's gon bare okay
1:07:19this next one I'm not going to over
1:07:21complicate it it's basically if somebody
1:07:22has vaginal dryness they're going to
1:07:23have low estrogen so this is obviously
1:07:25going to be a female but like maybe you
1:07:26think of postpartum breastfeeding
1:07:28dyseria pale dry vaginal mucosa 56 6
1:07:31weeks out, lactation causes increased
1:07:32prolactin that inhibits the G&RH that
1:07:34inhibits downstream later on estrogen.
1:07:36And the mechanism is important. It's low
1:07:38G&RH to low FSH to low LH to low
1:07:40estrogen. But then here in our practice
1:07:42question, we have elevated prolactin and
1:07:43that's what's causing the estrogen
1:07:44that's low. Mensy not resume since
1:07:46delivery. Low estrogen is definitely
1:07:48going to be correlated to vaginal
1:07:49dryness. All right. Here are the other
1:07:51answer choices. Increased luteinizing
1:07:52hormone would be PCOS, but here it's
1:07:54lactation. So this is suppressed.
1:07:56Decreased prolactin impairs milk
1:07:58production that would not cause pain
1:07:59during sex. Increased estrogen. So yeah,
1:08:01breastfeeding mothers can experience
1:08:03vaginal dryness. And it this isn't
1:08:05because of menopause at all. This is
1:08:06like prolactin stuff. In fact, it might
1:08:08explicitly test you on patients who are
1:08:11before menopause just so they can get at
1:08:13the prolactin's effect on the lowering
1:08:15of estrogen. But yeah, it's an
1:08:16interesting mechanism. Got to know it.
1:08:18All right, onto our next one. Here we
1:08:19have a 65-year-old man, a 5-year history
1:08:21of poorly controlled hypertension. And
1:08:23they're going to give him a CPAP and
1:08:24it's going to say, "Hey, what's going to
1:08:25change? just going to be a reduction in
1:08:26your blood pressure and that's
1:08:27interesting but you know usually the way
1:08:28the last get is we got like some
1:08:30patients usually it's going to be like
1:08:31kind of obese loud snoring daytime
1:08:33sleepiness obstructive sleep apnnea all
1:08:35those symptoms OSA and hypertension
1:08:37diabetes kidney dysfunction all that
1:08:38stuff and they're treating with a CPAP
1:08:40basically an OSA which is obstructive
1:08:42sleep apnnea you have repeated airway
1:08:44obstruction at night and you have drops
1:08:46in the O2 and that causes sympathetic
1:08:48surges and so the sympathetic surges
1:08:50cause a big swing in the blood pressure
1:08:51and that's sustained in daytime
1:08:53hypertension and so CPAP prevents the
1:08:55airway collapse and that reduces the
1:08:56apnecic episodes and that lowers the
1:08:58blood pressure and it's not going to be
1:08:59the pulse because that's not
1:09:00consistently lowered with CPAP
1:09:02creatinin. So sleep apnnea can
1:09:04technically can worsen your chronic
1:09:06kidney disease but the CPAP like doesn't
1:09:08fix it so that's not going to be the
1:09:10answer. Here's some good answer choices
1:09:11that you can choose between uric acid
1:09:13would be gout associations not CPAP
1:09:15related renal fun dysfunction is
1:09:16elevated creatinin but not with the
1:09:18CPAPs weight loss. CPAP alone does not
1:09:20cause weight loss. Glucose CPAP helps
1:09:22insulin sensitivity modestly but does
1:09:24not normalize it. All right, next we're
1:09:25going to talk about imunoglobulin
1:09:26switching. Isoype switching happens
1:09:28after the antigen stimulation. So you
1:09:30got the heavy and the light chains and
1:09:31they each have variable regions. So
1:09:33there's the the variable region is what
1:09:35you should know and that's unique,
1:09:36right? It's unique for every antibody.
1:09:37It never changes even after the V DJ
1:09:41switching. And the constant regions are
1:09:42determined by the class like IGM, IG,
1:09:44IGA, IG, IG. And the isotype class
1:09:47switching that happens after antigen
1:09:48exposure with help from the T- cells. So
1:09:50you have CD40 lian cytoines and the
1:09:52constant region of the heavy chain gets
1:09:54swapped. So IGM to IGG and the variable
1:09:56region that stays the same. The constant
1:09:58region are the parts that change during
1:10:00the isotype switching. So here's our
1:10:01question. 24-year-old man has a vaccine
1:10:04composed of an activated virus. 2 weeks
1:10:05later serum shows high levels of IGG
1:10:07specific to the viral antigen. This
1:10:09process involved genetic recombination
1:10:10of which portion of the imunoglobulin
1:10:12molecule? It's the constant region cuz
1:10:13class switching involves the constant
1:10:14one like going from IGM to G while
1:10:16preserving the VDJ recominated region
1:10:19allowing the B cell to retain its
1:10:20antigen specificity while gaining
1:10:22theector functions. All right, those are
1:10:24the other answers. But yeah, every
1:10:25single antibody that you have or that
1:10:27you make after vaccine starts with an
1:10:29IGM, even the IGG and the IGAs. All
1:10:31right, guys, we're almost there. We are
1:10:33so close to the finish line. All right,
1:10:34so here we have a 22-year-old college
1:10:36student is confused in her dorm room.
1:10:37Multiple empty cold medications nearby.
1:10:39Vitals are stable, but look at that.
1:10:412,100 ALT
1:10:442250.
1:10:46What's the mechanism of this hpattoxic
1:10:48effect? It is lipid proxidation due to
1:10:50the oxidative free radicals. This is
1:10:53acetaminophen overdose. Accumulation of
1:10:54napq toxic metabolite. Glutathine is
1:10:56depleted. Napqi causes lipid proxidation
1:10:59and death. So acetaminophen overdose is
1:11:01actually the most common cause of acute
1:11:02liver failure in the United States. And
1:11:04usually they have like a normal exam.
1:11:06The questions I like to ask this is like
1:11:07a younger student in college or somebody
1:11:09else. But but typically at normal doses
1:11:11it's safely handed this medication is
1:11:13safely handled by the phase 2
1:11:14conjugation like glucaronidation or
1:11:16sulfation but at overdose you get some
1:11:19saturation right you get excess
1:11:20acetaminophen that's shunted to the sip
1:11:22450 metabolism and so cip 450 makes
1:11:24napqi right it's a toxic metabolite and
1:11:27so what that does is it's normally
1:11:29detoxified by glutathione but in
1:11:31overdose glutathione storage get gets
1:11:32depleted and so now you have a lot of
1:11:34napqi and you get proxidation of the
1:11:36lipids in the cell membranes and the
1:11:38treatment is N acetal cysteine. That's
1:11:40the secret. All right, last question.
1:11:42And I really worked this one up.
1:11:44Basically, we have a 72year-old man or
1:11:46woman. As you can see in this
1:11:47demographic image, it could be either.
1:11:48And the reason I'm trying to do that is
1:11:50I want you guys to be exposed of not
1:11:51just locked into this one patient. I
1:11:52want to give you a range of the
1:11:54demographic that's affected because I
1:11:55think that's helpful as you take the
1:11:56step one exam to think about what types
1:11:58of patients you can and cannot see as
1:12:00opposed to just being like, "Oh, it's a
1:12:01woman this time. I could be a man." But
1:12:04here we're kind of testing like some
1:12:05moardial problems like congestive heart
1:12:08failure stuff and so it's going to be
1:12:09somebody elderly. But I digress. A
1:12:1172-year-old woman in this case history
1:12:13of long-standing hypertension presents
1:12:14with progressive dismia and orthopnia.
1:12:16We have a normal left ventricular
1:12:17ejection fraction but increased left
1:12:18atrial size and signs of impaired
1:12:20diastolic filling. Myioardial biopsy
1:12:22reveals normal sarcimeic structure but
1:12:23increased systolic calcium levels during
1:12:25diastily. Which of the following
1:12:26mechanisms is most likely impaired in
1:12:28this patient's cardiammyioytes? The
1:12:29answer is the function of the sodium
1:12:32calcium exchanger. That's diastolic
1:12:34calcium clearance. Now, especially if we
1:12:36look at heart failure with preserved
1:12:38ejection fraction, we have that poor
1:12:40mioardial relaxation, not the poor
1:12:42contraction. Contraction's fine, it's
1:12:44just the relaxation's not. So, you
1:12:46preserve the ejection fraction. We have
1:12:47a circa dysfunction and chronic
1:12:49congestive heart failure. So, it's the
1:12:51inability to restore the low calcium
1:12:53concentration during diastilly. So
1:12:55basically what's happening is like after
1:12:56contraction the calcium is not cleared
1:12:58from the cytoplasm and so you can't
1:13:00relax you just can't rel there's so much
1:13:02in the body that's like that you just
1:13:03can't let go and after contraction the
1:13:05calcium must be removed it has to be and
1:13:08that's mainly done by what how is this
1:13:10done by the sodium calcium exchanger it
1:13:13pumps the calcium out in exchange for
1:13:15the sodium to come in and that's how you
1:13:17restore the baseline before you can
1:13:19actually start the next beat of the
1:13:21heart right it's not the fast sodium
1:13:22channels cuz what do those guys do the
1:13:24fast sodium Those are the deolarization,
1:13:26right? That's that's phase zero. That's
1:13:27the fast deolarization. Inward rectifier
1:13:30potassium that stabilizes the resting
1:13:32potential. Lype calcium channels that
1:13:34lets the calcium in, right? That's the
1:13:36phase 2 plateau. And the ryanodine
1:13:38receptors that releases the calcium to
1:13:40trigger that. So the ranodine release,
1:13:42it's the sodium calcium exchanger.
1:13:44That's what's happening here. All right,
1:13:45guys. We did it. Man, dja vu. It's been
1:13:47fun kind of doing this twice. I've
1:13:49actually gone through and finished all
1:13:50the way to 90. So, I'm going to try to
1:13:52finish the rest of these as soon as
1:13:54possible. If you guys like this format,
1:13:55please let me know. Is that better
1:13:56lighting? Let me know as well. Should I
1:13:58have all of my lights on or is this
1:13:59better? Anyways, I hope you guys are
1:14:00doing super well. And remember, you're
1:14:02going to pass this exam in due time.
1:14:04Take care of yourselves. No feeling that
1:14:05you have is final. Make sure to
1:14:06prioritize your mental health. And let
1:14:08me just like show you guys something.
1:14:10You live in a tiny little blue dot.
1:14:12That's you. And all of your problems,
1:14:13they seem like they're the biggest in
1:14:14the world, but that's only because of
1:14:16your perspective, right? We don't have
1:14:18control of very much, but a change in
1:14:20our perspective is very easily
1:14:21accessible through meditation and
1:14:23gratitude. So remember, if you're
1:14:24feeling a little bit overwhelmed, take a
1:14:26pause before watching the next little
1:14:27couple videos, watch a movie, do
1:14:29something that's fun for you, lift your
1:14:30calcium oxide dumbbells, and remember,
1:14:32we don't have a lot of time here on
1:14:34Earth, so make the most of it. We'll see
1:14:35you guys in the next video. Adios. All
1:14:37these questions are original. Here we
1:14:38have a 25-year-old woman delivering a
1:14:40term male infant. She reports
1:14:42self-limiting illness with fever, rash,
1:14:44joint pains. Okay, so the mama is sick
1:14:45and she does not get medication. And
1:14:47then the newborn has a murmur. Oh no.
1:14:49Bilateral white pupilary reflexes. Okay.
1:14:51Some vision problems and also failed
1:14:52auditory. Okay. So vision, hearing that
1:14:54is a triad for reubella. It's cataracts,
1:14:57sensory neural deafness, and also a
1:14:59heart defect. In this case, looks like
1:15:00it's a patent arteriosis. So basically
1:15:02in this question, we got a mom who's got
1:15:04a mild illness like a fever, rash, and
1:15:05posturricular lympopathy. Aruricular, by
1:15:07the way, just means like the ear. So
1:15:09posterior to the ear lympadnopathy. and
1:15:11it's going to clear, but then the fetus
1:15:12is going to be in trouble because now
1:15:14the kid's going to have maybe like a
1:15:15blueberry muffin lesion with extra
1:15:17medularary hematopolesis in the skin.
1:15:19And there's actually a vaccine for this.
1:15:20It's the MMR vaccine. It's a live
1:15:21attenuated vaccine. And you just have to
1:15:23notice that triad of the cataracts, the
1:15:25hearing loss, and also the heart
1:15:26defects. And that's reubella, especially
1:15:28if it's like a torch infection. You
1:15:30might be saying, okay, cool beans.
1:15:31What's a torch infection? Well, that
1:15:33would be like toxo. Other is like
1:15:35syphilis, reubella, which is the answer
1:15:37to this question. C stands for CMV
1:15:39cytogly virus. And then H stands for
1:15:41HSV. And they present differently, but
1:15:42toxo you need to know it's like raw
1:15:44meats and then cat feces. And the big
1:15:45one for reubella is cataracts, PDA,
1:15:48blue- ray muffin rash. And they usually
1:15:50have an MMR that's not given, like a
1:15:52vaccine that's not given, and it should
1:15:54should be before pregnancy. And I
1:15:55figured these are kind of difficult
1:15:56sometimes, so I wanted to cover them.
1:15:58Like CMV, that's transplental vaginal.
1:16:01It could be like mild or monolike
1:16:03maternal symptoms. Now in CMV, you can
1:16:05also have cororedinitis. That's a big
1:16:06old fancy word for saying that you got
1:16:08inflammation of the coroid and the
1:16:09retina of the eye. It's part of the
1:16:10uvial tract. You can also be seen with
1:16:12the blueberry muffin rash for this one
1:16:13too. And it's the most common congenital
1:16:16viral infection. Now what's interesting
1:16:17about HSV as one of the torch infections
1:16:20is that actually occurs during pregnancy
1:16:22and you'll get painful genital vesicles.
1:16:24There's usually a vicular rash and
1:16:26encphilitis that's seen. So looking at
1:16:28our answer choices, a vicular rash is
1:16:31zoster or HSV would be CMV. and anemia
1:16:34with target cells that's a talismia so
1:16:36liver problems but yeah now you know
1:16:38torch the congenital infections that
1:16:39cross the placenta and affect the fetal
1:16:41development but some other ones that are
1:16:42important like HIV that can be
1:16:44vertically transmitted but it causes
1:16:46immuno deficiency usually not congenital
1:16:48malf formations in HIV HTLV which is the
1:16:51one right here this is a retrovirus that
1:16:53causes adult tea cell leukemia that can
1:16:56cause limb hypoplasia cutaneous scarring
1:16:58but this is not common unless you have
1:16:59an early pregnancy but these guys here
1:17:00on the right these guys are your torch
1:17:02pathogens like CM MV this a sensory
1:17:04neural hearing loss per ventricular
1:17:06calcifications microphily blueberry
1:17:08stuff herpes so herpes that's acquired
1:17:10during delivery you should think of a
1:17:11C-section if there's active lesions but
1:17:13yeah this causes vicular lesions
1:17:15seizures and sephilitis reubella was the
1:17:17answer to this cataract deafness PDA
1:17:19toxins raw me cat feces hydrophilis
1:17:21corbrenitis and intricraanial
1:17:22calcifications would be seen with toxo
1:17:24and syphilis goes with that saddle nose
1:17:26right there that's the other right so
1:17:27that's the snuffles disclamating rash
1:17:30like when the skin starts to just come
1:17:32off in scales also Hutchinson's teeth,
1:17:34saber shin, saddlen nose. All right, so
1:17:35hopefully that's a good little recap on
1:17:37all this stuff. These next two questions
1:17:38we're going to fly through pretty
1:17:39quickly. One is uncomplicated grief and
1:17:41I think the most important thing that
1:17:42you should do on step is distinguish
1:17:44this from depression. So uncomplicated
1:17:46grief can take many forms, but it's
1:17:48never going to have five of the sigaps.
1:17:50So five of eight for two weeks would be
1:17:52medical depression. But here we're not
1:17:54having medical depression, it's just
1:17:55uncomplicated grief. Medical depression
1:17:57is a bit more interesting. Being on the
1:17:58exam you have sleep changes, loss in
1:18:00interest, guilt, energy loss,
1:18:02concentration, difficulties, appetite,
1:18:03psycho motor and and these ideations.
1:18:05The sleep comes from the serotonin
1:18:06interest loss is from the dopamine. The
1:18:08guilt is a prefrontal cortex
1:18:10dysfunction. Energy loss HP axis and
1:18:13also females are twice as likely and so
1:18:15there's a hormonal influence as well.
1:18:16Cortisol is known instigator. There's
1:18:18something called the stress diiathesis
1:18:19model. Although people are thinking that
1:18:21electrical circuits and voltage has a
1:18:22lot to do with it these days, but
1:18:24they're not going to really test you on
1:18:25that. But yeah, cortisol might disrupt
1:18:26the HPA axis causing dysregulation of
1:18:28dopamine and serotonin which can cause
1:18:30mood disorder. But the stress diiathesis
1:18:33model says maybe there are instigating
1:18:34stress factors which can cause medical
1:18:36depression. But that's two weeks five
1:18:39out of eight of the the sigaps and is
1:18:41different than uncomplicated grief which
1:18:42can take many forms. Okay, that's all I
1:18:44wanted to say for that one. I think if
1:18:46you know the difference between
1:18:47uncomplicated grief and depression then
1:18:48you're going to be good to go. And so
1:18:50that's going to cover that topic for
1:18:51MBB29. Now for 53 I want to talk about
1:18:54colon malibancies. Now on step two
1:18:56especially less on step one but still
1:18:58may be seen. You have right-sided or
1:19:00proximal colon problems and then you
1:19:02have the leftsided which are more
1:19:03distal. The right sided is typically
1:19:05seen with iron deficiencies like iron
1:19:07deficiency anemia, fatigue, weight loss,
1:19:09all that stuff. Left side is usually
1:19:10bowel habit changes like obstruction,
1:19:12blood streaks, stools, things like that.
1:19:14On this right side it's going to be more
1:19:15of a silent bleeder. And by the way, the
1:19:17reason I'm drawing it right and left is
1:19:18because when you're practicing to become
1:19:19a physician, we always want to imagine
1:19:20that we have a person there, right? So
1:19:22this is their right side of their body.
1:19:23This is the left side. So just getting
1:19:24in a habit of that. When you're reading
1:19:25X-rays, you always got to flip it. So
1:19:26silent bleeding versus the apple core
1:19:28would be seen on the left side. Right
1:19:30side is a little bit more likely to be
1:19:31involved in lynch syndrome. So I'd think
1:19:33of that for step one. Whereas the right
1:19:35side more FAP, more sporadic. But it's
1:19:37also important to distinguish between a
1:19:39lot of these cancer kind of instigating
1:19:40syndromes like FAP familial adenomatus
1:19:44polyposis, Lynch syndrome, PJER
1:19:47syndrome. And with FAP there is a 100%
1:19:50risk of colonic cancer. And the key word
1:19:53you should think about lynch is
1:19:54microatellite instability. There it is.
1:19:56And you can have right-sided cancers
1:19:57endometrial ovarian risk. Marilyn Lynch,
1:19:59the CEO, right? Cervical endometrial
1:20:02ovarian risk. Pager that has the weird
1:20:05mutation associated with it. The STK 11.
1:20:08It's also automal dominant. They all
1:20:09are. A hemorratoma is a non-cancerous or
1:20:12benign growth that's made up of like an
1:20:14abnormal mixture of cells and tissues
1:20:15that are normally found in that area
1:20:17that it occurs. It's not cancerous and
1:20:19typically you find it incidentally and
1:20:21this can happen in various parts of the
1:20:22body but the lungs are typically where
1:20:24we note it and here with pure sugar you
1:20:26can also have mucaneous pigmentation so
1:20:28on the li like the lips the oral mucosa
1:20:31stuff like that there's a risk of GI and
1:20:33pancreatic and breast cancers as well
1:20:34but yeah apple core on the left side
1:20:36iron deficiency on the right side bowel
1:20:38changes would be a little bit more
1:20:39leftsided so like the pencil thin stools
1:20:41constipation that stuff micro satellite
1:20:43instability is the hallmark of lynch
1:20:44syndrome and then you should know for
1:20:46fap the APC C gene. It's like uphold
1:20:48carrot is how I like to think of that.
1:20:50Lynch has the MLH1 microatellite
1:20:52instabilities. Puge Jagger is the STK11
1:20:55mutations. So if you're feeling good
1:20:56about that, let's do your practice
1:20:57question. We have a 61-year-old man
1:20:59comes to the clinic with fatigue and
1:21:00shortness of breath on exertion. He has
1:21:01no history of GI bleeding, but routine
1:21:03labs reveal a hemoglobin level of 9.5.
1:21:06Colonoscopy reveals a mass in the
1:21:08ascending colon. Biopsy shows a
1:21:09moderately differentiated
1:21:11adenocarcinoma. Which of the following
1:21:13is the most likely underlying mechanism
1:21:14in this patient? Okay, the answer is
1:21:16going to be there's a DNA mismatch
1:21:18repair problem. Lynch syndrome,
1:21:20aphletoxin, you think aspiggilis,
1:21:22hpatoscellular carcinoma, hepatitis B
1:21:24also carcinoma there, HPV would be E6 E7
1:21:27associations and estrogen, breast cancer
1:21:30patho. So yeah, many causes of colon
1:21:32cancer develop without any symptoms at
1:21:34all. And so if you see a new iron
1:21:35deficiency like in this patient and it's
1:21:37going to be like an older man, maybe
1:21:39like a post-menopausal woman, then maybe
1:21:41you should think of colon cancer until
1:21:42you're proven otherwise. And there are
1:21:44two major pathways that drive this.
1:21:45There's the adenote carcinoma sequence
1:21:47that involves APC crass p-53, right? APC
1:21:51then crass mutation then loss of p-53.
1:21:54That's the adenoma carcinoma sequence.
1:21:56And then there's the micro satellite
1:21:58instability. That is the MSI pathway.
1:22:01And in the MSI pathway, that's the
1:22:02mismatch repair problem with Lynch
1:22:04syndrome. And right sided tends to bleed
1:22:07while the leftsided tends to obstruct.
1:22:09So here we had a right-sided mass. So,
1:22:11it's probably going to be an MSI pathway
1:22:13stuff. So, it's a mismatch repair gene
1:22:15problem. All right. The next topic is
1:22:16anytime you have a mean, median, and a
1:22:19mode question, you should just be super
1:22:20thorough. They might ask you, hey, what
1:22:22would change if we have like a.5 and 6,
1:22:26and we change this.5 to a 6. Well, then
1:22:28it'd be two point sixes and so the mode
1:22:30would change and also the median and the
1:22:32mean would both rise, right? So, just be
1:22:34super thorough. They're super easy
1:22:35questions. Don't miss those points.
1:22:37That's all I needed to say for that
1:22:38question. 54. Okay, for next question we
1:22:40have a 17-year-old girl who is evaluated
1:22:42for prolonged menstrual periods and easy
1:22:44bruising. She reports frequent nose
1:22:46bleeds in childhood and gum bleeding
1:22:47during dental cleanings. So we're
1:22:49already thinking of von Wilbrands which
1:22:50the following is a primary defect. It's
1:22:52the decreased platelet binding to the
1:22:54subendothelial collagen. Impaired
1:22:55platelet adhesion is what you should
1:22:57think of and vonilbrin factor normally
1:22:59tethers these platelets to the
1:23:00subendothelial collagen of the GP1B. The
1:23:022B3A is Glman's and Glansman's is a big
1:23:05old name and so it has more numbers
1:23:08whereas like Bernard Soier BS there's
1:23:11only one B in that. So BS Bernard and so
1:23:14I like to think of that's GP 1B. I
1:23:16wonder if that's an answer choice. No
1:23:17it's not but you get the idea. Gland's
1:23:18been super long name so it has a super
1:23:20long GP 2B 3A and that's all you really
1:23:22need to know. It's the aggregation
1:23:23problem though not adhesion. aggregation
1:23:25feels like it has more numbers
1:23:26associated than adhesion does and that's
1:23:29why I think of it as 2B3A as opposed to
1:23:31just the one auto antibodies ITP
1:23:34thrombopetin megaitic thrombocyopenia
1:23:37that's a low platelet count and vitamin
1:23:38K would be 27910 and so you have a
1:23:41normal platelet count there it's just
1:23:42that there's increased bleeding time
1:23:43because the the pllets are there they
1:23:45just can't stick you also have mucaneous
1:23:46bleeding so nose bleeds minid gum
1:23:49bleeding you have increased PTT because
1:23:51vonilam carries and stabilizes the
1:23:54factor eight and wrist seed and tests
1:23:56are abnormal that means it's defective.
1:23:57Bernardilier the giant and I wanted to
1:23:59throw Chidiac as well. That's just
1:24:00infections in albina. It's kind of
1:24:01unrelated but sometimes people mistake
1:24:03that because it also has the giant stuff
1:24:05but this is a different type of giant
1:24:06and glandsman's of course we mentioned
1:24:08that's when you have no aggregation
1:24:09whereas these guys are no adhesions. All
1:24:11right for the next question here we have
1:24:13a 67y old man presenting with fatigue
1:24:16generalized bone pain. He's lost 8 lbs
1:24:18unintentionally. So maybe some type of
1:24:20cancer. Oh we got renal issues as well.
1:24:22Hypercalis. I think this is multiple
1:24:24myoma. And so the answer is going to be
1:24:27D osteoclastic activation by tumor
1:24:29cytoines. Indeed this is multiple myoma
1:24:31which does not have PTHP that's squamous
1:24:34cell stuff vitamin D analoges granulatus
1:24:36disease sarcoid stuff parathyroid would
1:24:38not have light chains GI calcium
1:24:40absorption is vitamin D excess these
1:24:42benones are the white chains you see
1:24:44bone pain and multiple myoma and low
1:24:46formation there's the crab calcia renal
1:24:48anemia bone lesion this one's super
1:24:50pathommonic but you could see the
1:24:52macrofase infiltration stuff so IL1 is
1:24:54elevated TNF alpha MIP1 these are all
1:24:57the kind of big giveaways for the
1:24:59mechanism action for multiple myoma also
1:25:01the rank L through the activation of
1:25:03NFCappa B you cause an increase of the
1:25:06osteoclass causing these litic bone
1:25:07lesions which is indicative of multiple
1:25:10myoma okay so that's how you think and
1:25:11diagnose multiple myoma on test A for
1:25:13step one you might see like IL1 TNF
1:25:16alpha factors that stuff okay in our
1:25:19next question we have a 31-year-old
1:25:20woman presenting with intense vulvar
1:25:22itching burning and thick white vaginal
1:25:24discharge she recently completed a
1:25:26course inclinia for dental abscess
1:25:29Pelvic exam shows athemma of the vulva
1:25:31and clumpy white discharge. This is
1:25:32Canada vulva vaginitis. 4.3 is the pH
1:25:35and first line is fluconazol which
1:25:37causes the inhibition of argustal
1:25:39synthesis via cytochrome P450
1:25:41inhibition. All right. There are a
1:25:42couple of antifungals and things we got
1:25:43to know. So asils that causes the
1:25:46inhibition of erostral synthesis. So no
1:25:48argust there. Pines like that those will
1:25:50bind the aostral and cause the pore
1:25:51formation. There you should think of
1:25:52amphostatin aocandons. These guys are
1:25:55big big players. they inhibit the
1:25:57betalucan synthesis and so it will just
1:26:00cause no cell wall to exist. So if a lot
1:26:02of the aols and the polyines like
1:26:03nastatin and stuff they aren't working
1:26:05then maybe consider this drug so you can
1:26:07just literally wipe out the cell wall.
1:26:08The stopping of the D NA and the RNA is
1:26:11the job of fluticosine. If you give them
1:26:13turbinophene then it causes a buildup of
1:26:14squaline which is toxic that's used for
1:26:17latinia infection. So antifungal
1:26:18mechanisms like are used for vulva
1:26:20vaginal candidasis and you know it was
1:26:22candidasis because of that thick white
1:26:24cottage cheese stuff. Also the pseudoh
1:26:26highay on the koh prep tells you it's
1:26:29diagnostic under the microscope and the
1:26:30pH that is low like 4.5 or less will
1:26:33distinguish it from the or bacterial
1:26:35vaginosis and then the recent
1:26:36antibiotics or contraceptive use those
1:26:38are common triggers here and so you use
1:26:40an ail antifungal that targets a
1:26:43synthesis through the sip 450 inhibition
1:26:45you might also have some interesting
1:26:46associations and risk factors like one
1:26:48of them is actually diabetes diabetes or
1:26:50imunosuppression right it'll impair your
1:26:52host defenses pregnancy is one because
1:26:54you have hormonal changes Fluconazole,
1:26:56miconazole, those guys inhibit the 14
1:26:58alpha demethyl which is a sip 450
1:27:01enzyme. Arrogostral is the fungal cell
1:27:04membrane component. It's like kind of
1:27:05like cholesterol in humans. This is a
1:27:07good way to think about it. And so
1:27:08Canada normally colonizes the vagina as
1:27:10part of the flora and the antibiotics
1:27:11and the hormonal changes decrease the
1:27:12lactobacilli that increases the Canada
1:27:15overgrowth. And so then Canada starts to
1:27:16make those pseudohate in the tissue and
1:27:18ailles like fuconazole inhibit the sip
1:27:20450 dependent demethyls and that causes
1:27:23decreased elgostral synthesis and also
1:27:24membrane dysfunction and so it's a
1:27:26fungatic effect right the yeast just
1:27:28can't grow they can't replicate it's
1:27:30amazing and usually on the koh prep
1:27:32you'll see the budding yeast and
1:27:33pseudohifa so yep give them fucconol and
1:27:36know that it inhibits the demethylation
1:27:38through the sip 450 so yes it's the
1:27:40fungus among us kind of like the Pokemon
1:27:42but yep your asils they target the
1:27:44fungal Sip 450 14 alpha demethylise
1:27:48resistance can happen through e-llex
1:27:50pumps. Sip 450 is partially affected so
1:27:52it can interact with warrin and phenotin
1:27:54and those 450 susceptible medications.
1:27:57Penetrates the CNS used in crypto Canada
1:27:59coxidioconazole is used in hysto. Here's
1:28:02another practice question. Start on
1:28:03medication. How does it work?
1:28:05Bloxenostral 14 alpha demethylase.
1:28:07Membrane pores is amphosaran b or
1:28:09neistatin which there they are on this
1:28:11nice sheet here. Glucan synthes is the
1:28:13aminoins that stop the the cell wall.
1:28:15These synthes 5 fu flucidazine stops
1:28:18nucleic acid synthesis and squaline
1:28:20epoxidation. Turbinophene inhibits
1:28:22squaline epoxidase. So causes the
1:28:23squaline growth kills youria. For the
1:28:26next question you might see somebody
1:28:27with I've seen a lot of questions on
1:28:28this on on different MMEs. Blisters how
1:28:31do blisters happen? So the pathophys of
1:28:32the blisters is you get mechanical
1:28:34thermal infectious injury. You lose the
1:28:36desmosome integrity. Now you get the sub
1:28:38epidermal like in bololis pmpagoid seen
1:28:40in frictions and burns. Here's a
1:28:42practice question. 76-y old man large
1:28:43tense blisters. Nakolski sign is
1:28:45negative. Auto antibodies against the
1:28:46hemismal proteins. Bispmphoid. Negative.
1:28:49Nicoleki positive would have been the
1:28:51shearing on the rubbing which is pmpagus
1:28:53vulgaras not bullis. So yeah those
1:28:55hemisesomes
1:28:56they are super important. They anchor
1:28:58the keratinocytes to the basement
1:29:00membrane. That's just like the cells
1:29:01that produce keratin. The key features
1:29:02are linear IGG and C3. Here's another
1:29:05practice question. 74y old woman several
1:29:07large tense blisters on her trunk. She's
1:29:09got linear deposition of IGG. What's
1:29:11going on? Dysfunction of the anchors to
1:29:13the basal cell to the basement membrane.
1:29:15Bulis pmpagoid. It's when you attack the
1:29:16hemism. Think of the H attacking
1:29:19attaching hemi. Attach it to the
1:29:20basement membrane. Now the linkage
1:29:22itself the desmosomes are attacked to
1:29:23pimpus vulgaras. Neutrifil migration
1:29:25selectance and integr homing CLA and
1:29:28tight junctions would be in the
1:29:29intestinal and the renal epithelium. So
1:29:31seen in elderly, itching, that kind of
1:29:33stuff, blistering. All right, this one's
1:29:36really interesting. Here we have a
1:29:3732-year-old man presenting with rapidly
1:29:38enlarging thigh mass. Biopsy has a
1:29:40pleomorphic polyiffiated cell with scan
1:29:43cytoplasm and hyperchromatic nuclei. We
1:29:45have strong positivity for Desmond. All
1:29:47right, so Desmond, what is that? Muscle.
1:29:49Anytime I say the word muscle, I got to
1:29:50do some exercises. So yeah, it's smooth
1:29:51muscle, right? Desmond is a muscle
1:29:53specific intermediate. And here you
1:29:54really have to know your tissue markers,
1:29:55right? So on muscle tumors, you have
1:29:57Desmond. And I did this beforehand,
1:29:58right? Those guys are the intermediate
1:30:00filaments in the muscle cells. They're
1:30:02positive in like rabdtomyolysis or
1:30:04leoyio sarcomomas. Anything with a myio
1:30:06in it, right? Myo desine. The cytoerotin
1:30:08is in the epithelial cells. That's
1:30:10positive in carcinomomas, right? The
1:30:11skin, the glands. For the nerves, you
1:30:13should think of the central, the
1:30:14peripheral neuronal support, gal cells.
1:30:16And the marker there that you should
1:30:18probably know is GFAP. And GFAP is an
1:30:19astroy marker. So glyobblastoomas,
1:30:22appendimomas. And the last one I think
1:30:24I'll just add for completion is S100.
1:30:26That's for melanocytes like melanomas,
1:30:28langangeran cells, schwanomomas. So they
1:30:30could ask you this in a number of ways.
1:30:31They could say we got like a
1:30:33six-year-old boy. He's got a big old
1:30:34mass and it's spindle-shaped tumor. It's
1:30:36got cross striations and it's positive
1:30:38for myoggenine and Desmond. And then
1:30:41they'll say, "Hey, what's the
1:30:42diagnosis?" And you're going to say it's
1:30:43a rabbi saroma or something like that
1:30:45with a Mayo in it because of the Desmond
1:30:47Gold.
1:30:48>> All right, for this next question, I
1:30:50think it's important to know just what
1:30:51is peritonitis like what even is it?
1:30:54Well, I guess if you break apart the
1:30:55word, you know, it's peritonitis is an
1:30:57inflammation ititis of the paritineal
1:30:58lining of the abdominal cavity. And
1:31:00you're going to see just like acute
1:31:02painful and life-threatening
1:31:04presentations. Now, it can be primary,
1:31:05it can be secondary. So, primary is like
1:31:07cerosis or like a nefertic syndrome. And
1:31:10secondary would be like a a perforation
1:31:11or a GI tract thing. Maybe you have a
1:31:14like a peptic ulcer that that ruptures
1:31:16or you have appendicitis,
1:31:18diverticulitis, some sort of a trauma.
1:31:20Or you could even have a tertiary
1:31:22peritonitis and that's after you give
1:31:24treatment. So there's post-operative or
1:31:26immunocmpromised patients who will
1:31:27suffer from this. And the big thing here
1:31:29is the rebound tenderness. So if you
1:31:31lift the hand, oh that's more pain than
1:31:33it was when you were pressing down,
1:31:34right? That is rebound tenderness.
1:31:36Guarding and rigidity. That's the
1:31:38involuntary muscle tightening. There's
1:31:40also a board-like abdomen that people
1:31:42describe. It's classic for the surgical
1:31:44abdomen. And you'll you'll have absent
1:31:46bowel sounds. So it's a it's a paralytic
1:31:48ilas. You could also have diffuse
1:31:49abdominal pain, fever, tacic cardia. The
1:31:52way to think about this on on board's
1:31:53questions is okay, there's going to be
1:31:54like a trigger. Maybe there's a GI
1:31:56perforation. Maybe there's a bacterial
1:31:57infection. Maybe there's a leak of the
1:31:58bile. Who knows? There's irritants in
1:32:00the peritineal cavity, right? There's
1:32:02bacteria, there's acid, there's feces,
1:32:03who knows what? Maybe somebody had their
1:32:06stomach cut open and cat feces got into
1:32:08I don't know a million things, right?
1:32:10Massive inflammatory response. And then
1:32:12you get excedate and neutrfils that
1:32:14flood the cavity. Okay, what is excate?
1:32:16Well, that's any mass of cells or fluid
1:32:18that has seeped out of the blood
1:32:19vessels, especially in inflammation.
1:32:21That's what excavate means. So, you have
1:32:22that and neutrfils all up in your cavity
1:32:25causing pain, edema, paralytic ilas. And
1:32:27so, the signs you look for would be
1:32:29fever, hypotension, and also maybe
1:32:30shock. And you'll especially have shock
1:32:32if you don't treat this thing. So, with
1:32:33that being said, we have a 68-year-old
1:32:35man. He's got diffused abdominal pain,
1:32:37free andal air, and thickened sigmoid
1:32:39colon consistent with perforated
1:32:40diverticulitis. There it is. Boom.
1:32:42There's the trigger we talked about.
1:32:43Autopsy shows a yellow tan strands of
1:32:45the liver capsule in the paritinium.
1:32:47Which of the following is most likely
1:32:48component? It's fibbrin. So he's got
1:32:50this perforated bell and I'll move so
1:32:51you can see these explanations.
1:32:52Bacterial parasiticis. He's got the
1:32:54oxidate. Inflammatory stuff is happening
1:32:56and it's fibbrin that traps the
1:32:57bacteria. The fibbrin's like, "Oh my
1:32:59gosh, guys, we're having a problem.
1:33:00Let's like trap this bacteria so that it
1:33:01can't spread. But if you have like
1:33:03fibbrin on your tissues, then that's
1:33:05going to cause some problems. It's not
1:33:06type four collagen. That's the basement
1:33:08membrane stuff. It's not elastin. That'd
1:33:10be the stretchiness. Not lamin. Laminine
1:33:12is a big old carbohydrate group that's
1:33:13seen just on the extracellular surface
1:33:15of pretty much every single organism.
1:33:16And hyaluronic acid that's good for
1:33:18retaining moisture. I don't know if you
1:33:20guys have ever used that. It's like a
1:33:21kind of like a moisturizer. It's seen in
1:33:23like your eyes, like all over your body.
1:33:24Keeps the moisture going. All right, for
1:33:2661, anytime you see the word eskemia and
1:33:28they're talking about the the renal
1:33:30tubules, then you should always think of
1:33:31the proximal convoluted tubial. And
1:33:33that's just always the case. And that's
1:33:35all I want you to know for 61. Super
1:33:36easy. I'm not going to harp on something
1:33:37if it's not important or could be stated
1:33:39very quickly and succinctly. Next, on
1:33:41that same vein, what do you do if you
1:33:43have a lot of kind of pale looking, weak
1:33:44looking red blood cells? Well, you just
1:33:46think immediately of iron deficiency
1:33:48anemia. Iron deficiency anemia can be
1:33:49caused by a lot of things like
1:33:50gastrointestinal blood loss. It's
1:33:52microitic, hypochromic, you know, pale.
1:33:54You're just losing that iron, right? So,
1:33:56it's just pale. They're it'll look like
1:33:58this, like they're kind of hollowed out
1:33:59a little bit. And I know you guys want a
1:34:01practice question, so I'm going to go
1:34:02ahead and give you one here. 76-y old
1:34:04woman has exertional fatigue. Look at
1:34:06that. Anemia, MCV is low. Microitic.
1:34:10What is the underlying cause? Bleed.
1:34:12It's a GI bleed. Microitic, hypochromic,
1:34:14low feritin, iron deficiency anemia
1:34:16every single time. You confirm this with
1:34:17colonoscopy. Bada bing, bada boom. Here
1:34:19are the reasons that it's not these
1:34:20things. B12, hyper segmented,
1:34:22autoimmune, spheric, militus plastic
1:34:24would have pansopenia, bone maroplasia,
1:34:26has low stuff. Lover tick pansopenia.
1:34:28All right, 63. I'm just going to remind
1:34:30you of the same question of like 61 just
1:34:32PCT eskeeia. They're es schemic parts of
1:34:35the body that you need to worry about,
1:34:36but if it's in the kidneys, PCT every
1:34:38time. Next we're going to go to 64. Here
1:34:40we have a 58-year-old male. Chronic
1:34:42right flank pain recurrent fevers foul
1:34:44smelling urine. He has a history of
1:34:45multiple urinary tract infections. Large
1:34:48radiopic stone conforming to the shape
1:34:50of renal kalouses pH of 8.2 lucasite
1:34:53estray is positive and stuvite crystals.
1:34:55What's the most likely positive
1:34:56organism? What's causing this? The big
1:34:58thing here is this pH that's super basic
1:35:00and the one that you should think of
1:35:01then is proteus morabilis. Also other
1:35:03proteuses like proteus vulgaras but
1:35:05basically proteus is a uras positive
1:35:08organism that increases the pH you get
1:35:10the struite stones it's not ecoli that'd
1:35:13be the most common uti bug not myopplasm
1:35:15that lacks the cell wall it's not
1:35:16interaccus doesn't produce uras and not
1:35:19clubsella it's less common in the stone
1:35:21formation and really if they're looking
1:35:22at something basic than do proteius
1:35:24marabilis all right for the next one
1:35:26we're going to distinguish between these
1:35:27two slip capital femoral epithesis and
1:35:29oshkid slaughters right so what's the
1:35:31difference well the age group can be
1:35:33similar, but the slipped is usually in
1:35:35growth spread periods and Oshkot is for
1:35:37athletic kids. And that's pretty much
1:35:39all you need to know. Like that alone
1:35:41will help you distinguish Oshkot
1:35:42slaughters because you you'll be
1:35:43athletic in that one. And then typically
1:35:45the body type is obese. In a slip cap,
1:35:47you have displacement of the femoral
1:35:48head whereas this one's tractionitis.
1:35:50Basically, it's like the growing pains
1:35:52but with the particular place that the
1:35:54muscle attaches cuz these kids are
1:35:56strong. They're athletes. Okay, that's
1:35:57the big difference here. We're just
1:35:58going to look at some clinical if you
1:35:59see Ashklaughter sporty teen below the
1:36:01knee. All right, in this next question,
1:36:02we have a 2-year-old boy brought to the
1:36:04pediatrician due to frequent re
1:36:06respiratory infections, satosinly,
1:36:07developmental decay. And we see coarse
1:36:09facial features, cornal clouding, and we
1:36:11have a deficiency of alpha lyon.
1:36:14This is the giveaway here. And the
1:36:16corial clouding, so it's hurlers. It
1:36:18can't be hunters because hunters need
1:36:19their cornea to see. So it has to be
1:36:21hurlers. It ain't why? Cuz that would be
1:36:23a mano6 phosphate thing. So it's not
1:36:25that gouch taste. Here's the explanation
1:36:27for those glucoserite. Glucosidase
1:36:30deficiency is gouch. You'd have apatos
1:36:31splomegaly and bone crisis and tay saxs.
1:36:34I pretend that this is an X and I say
1:36:35hex. Tay-ax and that causes cherry red
1:36:38noat splenomegaly. That's the big deal.
1:36:41Easy peasy lemon squeezy, right? Sure
1:36:42thing, bubbing. All right. Next up here
1:36:44we have a 24-year-old woman comes to the
1:36:46ED with nausea, vomiting, abdominal
1:36:48pain, history of type one examination.
1:36:50She has she's tick tic typnic and
1:36:52dehydrated. Which of the following
1:36:53explains the initial evaluation a drop
1:36:54in the potassium? So yeah, her potassium
1:36:56concentration is going to drop. Anytime
1:36:58you see that you should probably be
1:37:00thinking about insulin and the answer is
1:37:01indeed potassium shifting out of the
1:37:03cells due to insulin deficiency. She has
1:37:05that acidic thing going on. It's DKA
1:37:07hypoglycemia ketosis in ion gamab
1:37:10metabolic acidosis. Now normally insulin
1:37:12deficiency prevents the potassium
1:37:13uptake. So you have too much potassium
1:37:15and acidosis causes the hydrononeium
1:37:17ions to shift in the cells and then the
1:37:18total potassium is low because of the
1:37:20loss through osmotic diaresis and
1:37:22vomiting. It's not B because may
1:37:24increase but it's not the driver and
1:37:26diaries contributes to body loss not
1:37:28initial elevation and poor intake can
1:37:30worsen hypocalemia. Insulin helps it
1:37:31shift in. Now I also wanted to do some
1:37:34pituitary stuff and hypothalamus stuff
1:37:35that the hypothalamus stimulates FSH and
1:37:37LH. The anterior pituitary stimulates
1:37:39spermatogenesis in the males and
1:37:41follicular growth in the female.
1:37:42Interior pituitary also makes LH which
1:37:45stimulates the latig cells and then the
1:37:46gonads themselves make the testosterone,
1:37:47estrogen, estrogen and progesterone. Now
1:37:50the sererati cells those secrete inhib
1:37:52and that inhibits FSH. The granulosa in
1:37:55the female makesh hormones. So and
1:37:57that's like the granulos in the female.
1:37:59Just wanted to go over some of those and
1:38:00also some other commonly confused ones
1:38:02FSH. There you get cerolely cell
1:38:04activation and sperm production with
1:38:05inhib lh and that's testosterone
1:38:07synthesis and the testosterone is
1:38:10actually a negative hback is a negative
1:38:12feedback instigator of the testosterone
1:38:14causes negative feedback and also male
1:38:16secondary sex characteristics and
1:38:18inhibin inhibits FSH only. So the names
1:38:20kind of do what you think they do which
1:38:22is fortunate. All right. Next, you have
1:38:23a 29-year-old man, 3we history of
1:38:25painless bilateral languinopathy and
1:38:28single painless ulcer, unprotected
1:38:30intercourse, multiple partners, meopri
1:38:32therapy is what? So, this is bacterial
1:38:33transepidase. But we need to know
1:38:35because of that painless genital ulcer
1:38:37jinker. The painless bilateral
1:38:39impenopathy is primary syphilis that's
1:38:41caused by a trapema. And the first line
1:38:43is always going to be penicellin because
1:38:44it binds to the bacterial transepase and
1:38:46disrupts the cell wall integrity. It's
1:38:48not 30s. It's imunoglycosides. It's not
1:38:50first line for syphilis. It's not DNA
1:38:52dependent RNA pulymerase. It's rafampen
1:38:54stuff for TB. It's not dihydropterate
1:38:57synthes. It's inhibited by sulfonomides.
1:38:59And it's not micolic acid. That's the
1:39:01isinasid for tuberculosis. It's a
1:39:03penicellin cell wall synthesis
1:39:06inhibition through bacterial
1:39:07transepidase binding. All right. Next,
1:39:09we have a six-year-old boy brought to
1:39:10the position due to persistent abdominal
1:39:12mass during routine checkup. They
1:39:13noticed he's got a smooth, firm,
1:39:16non-tender mass. In abdominal
1:39:17ultrasound, we have a 9 cm solid renal
1:39:19mass. Genetic analysis shows deletion of
1:39:2111 p13 mutation in the gene encoding
1:39:24which protein the answer is a so this
1:39:26was a kiddo so it was wilms tumor
1:39:27nephroplast we had a large unilateral
1:39:29flank pain histologology shows blastimal
1:39:31the blue cell components and it's the
1:39:34WT1 gene which is the paired box the
1:39:36pack domain WT1 is located right there
1:39:38on 1113 you know that if you watch our
1:39:41chromosome video has the you think of
1:39:43that as like the 11 L Wilms all right
1:39:45it's not polycystin that's going to be
1:39:47autotoal dominant polycystic kidney
1:39:49disease it's type four that's alpport
1:39:51not epithelial sodium channel that's in
1:39:52little syndrome and it's not ura
1:39:54transport that affects the concentrating
1:39:56ability this is Wilms all right and the
1:39:58last question here 29-year-old man with
1:40:00HIV presents with the follow-up after
1:40:02recent change in his anti-retroviral
1:40:04therapy regimen recent lab has
1:40:05significant decline the viral load and
1:40:06increasing CD4 T- cell count while
1:40:08Tegravir is most likely to inhibit which
1:40:11of the following steps tegra integration
1:40:14it's right in the name the answer C so
1:40:16there are some steps to the HIV
1:40:17replication cycle that are worth knowing
1:40:19First you have to attach right that
1:40:20attachment you have GP120 binding to CD4
1:40:24and those would be your entry I mean
1:40:26that's your entry step and so you block
1:40:27it with entry inhibitors like Mario
1:40:29veroke or any of the CCR5 antagonists
1:40:33and then we have fusion and I love these
1:40:35cuz it's right in the name infertide
1:40:37right it's when you try to fuse with the
1:40:38host membrane so you have to stop the
1:40:40fusion with the things that have few in
1:40:42their name fusion and then there's the
1:40:43uncoding process and another big one is
1:40:46any of the navier those are proteus is
1:40:49inhibitors right and the proteiase
1:40:50inhibitors they affect that protein
1:40:53processing phase so with the HIV drugs
1:40:55when in doubt it's all in the name
1:40:57integra it inte helps with the
1:40:59integration right it's used in that step
1:41:01in feveride the fusion step right the
1:41:04neers you're never going to be able to
1:41:06protein process that's how you remember
1:41:07them all right we just did 51 all the
1:41:10way to 70 if you found this helpful like
1:41:11and subscribe we'll see you guys in the
1:41:13next one hello everybody welcome back
1:41:15today we're on question 71 I've heard
1:41:16all of your feedback the majority of you
1:41:18guys wanted no green screen so you can
1:41:20see all the fun stuff going back in the
1:41:21room around question 71. I've also been
1:41:24working on adding AI generated images
1:41:26which should go roughly with each
1:41:27question. The image will correspond to
1:41:29somebody who could have a similar
1:41:30condition and I'll explain each one. So
1:41:32we have a 6-month old boy evaluated for
1:41:34weight gain current respiratory
1:41:36infection. All right, so you can see it
1:41:37just updated on exam heistnic mild
1:41:40subcostal retractions cardiac
1:41:41oscultation reveals grade four to six
1:41:43holystolic murmur at the lower. So, it's
1:41:45that left sternal border and that hollow
1:41:47systolic 4 to6 sound which really queue
1:41:50you into that diagnosis. Now, they could
1:41:51have asked this a different way. So,
1:41:52here's a new question. Here we have a
1:41:53six-month old infant broadband for
1:41:55evaluation of poor feeding and frequent
1:41:58respiratory infections. Kipnic
1:41:59hippamegaly grade four to six holostolic
1:42:01murmur at the left lower sternal border.
1:42:04Now, they're saying which complication
1:42:05is most likely the condition if left
1:42:07untreated. So, we established this is a
1:42:09VSSD. So there's chronic increased blood
1:42:11flow through the pulmonary vascule and
1:42:13that's due to this left to right shunt.
1:42:15And so the answer is going to be
1:42:16pulmonary arterial hypertension. Okay,
1:42:18here's your explanation. Here's some
1:42:20other ones why the wrong aortic
1:42:21dissection is not associated with
1:42:22congenital septile defects. Aortic
1:42:24valve. For that one, you should think of
1:42:26abnormal or previously damaged heart
1:42:27valves and dental procedures. That's
1:42:29subacute associations. So for this next
1:42:32question, there's a 19-year-old man with
1:42:33a known VSSD and on exam, he has a new
1:42:36holystolic murmur, splinter hemorrhaging
1:42:38of his fingernails. He had dental
1:42:40cleaning that is going to be
1:42:41streptococcus virardance. It's the most
1:42:43common cause of subaccute bacterial
1:42:45endocarditis on abnormal valves.
1:42:47Stafarius causes acute endocarditis on
1:42:50normal valves. Interaccus is seen in the
1:42:52elderly with GU procedures. Staff
1:42:54epidermitis is in prosthetic valves and
1:42:56sudamonus would be rare but in IV drug
1:42:58use it would have rapid severe valve
1:43:01destruction. All right. So the answer is
1:43:02going to be dopamine but there's a
1:43:04really strong argument for serotonin as
1:43:06well if you chose that. Now it's not
1:43:07tyroine. That's an amino acid precursor
1:43:09which is not metabolized by an MAO which
1:43:12by the way MAO inhibitors block the
1:43:14mitochondrial monoamine oxidase and that
1:43:17degrades these things. So if you block
1:43:19it then you have increased serotonin or
1:43:21epinephrine dopamine and epinephrine or
1:43:22you could have serotonin syndrome and
1:43:24other problems like that. But this is
1:43:25seen in treatment resistant depression
1:43:27that's improved with phenylene and
1:43:29transcycloproine transipamine. So you're
1:43:32blocking the monoamine catabolism and
1:43:35they mentioned aged cheese and red wine
1:43:37along with severe headaches and
1:43:38hypertension because tyramine escapes
1:43:40the first pass mechanism when m is
1:43:42inhibited. So tyramine containing foods
1:43:45like aged meats, cheese, wine, soy those
1:43:48are contraindicated also like tremodol,
1:43:50St. John's ward, linenolid, those can
1:43:52cause serotonin syndrome. And so this
1:43:54mau normally is going to daminate 5HT,
1:43:57norepinephrine, you know, DA,
1:43:59epinephrine, but you inhibit it. And so
1:44:01you have increased vicular stores and
1:44:03it's not serotonin, though that could
1:44:05increase since we're more dealing with
1:44:07our hypertensive crisis, not as much
1:44:09serotonin syndrome. You know, they could
1:44:11have said something like epinephrine as
1:44:12well, but that hypertensive crisis is
1:44:14less serotonin and more doperic or
1:44:16epinephrine associated. Okay, so in this
1:44:19question, we have an 8-year-old girl.
1:44:21She's been tripping while walking, got
1:44:22double vision when looking to the left,
1:44:24so she can't look to the left. Her
1:44:25parents also know been dragging her
1:44:26right leg. So her right leg is dragging.
1:44:28And on exam, she's got impaired left eye
1:44:30abduction and broad-based unsteady gate,
1:44:32increased muscle tone on the right lower
1:44:33limb with brisk reflexes, which the
1:44:35following is the diagnosis is pyocitic
1:44:37astroytoma, the pawns, slow growing
1:44:39brain tumor, astroytoma. So she's got
1:44:42the left abducence nerve policy.
1:44:44Cerebral at taxexia, right sided, upper
1:44:45motor neuron science, not gamay, that's
1:44:47ascending paralysis. Gixit taxia,
1:44:49genetic and symmetric gate taxia.
1:44:51Neuroblast would have lower motor neuron
1:44:53science, not the brain stem stuff. And
1:44:55cerebilitis causes bilateral taxia after
1:44:58a postviral infection. Cool beans. So
1:45:00yeah, not the ascending, not bilateral
1:45:02problems. We see the brain stem
1:45:04problems, not spinal metastasis because
1:45:06that would cause lower motor neuron
1:45:08problems. And acute cerebilitis would be
1:45:10after some sort of an infection. And so
1:45:11our answer is A. And I think my
1:45:13microphone cut off on this one. So I'm
1:45:15going to redo it. A 22-year-old man will
1:45:17be shown up there. They have severe
1:45:19onset abdominal pain and vomiting for 3
1:45:21hours. So there's our guy. He has no
1:45:23past medical history. Abdomen is
1:45:25distended. Contrast shows his dadum does
1:45:27not cross the midline. So he's got a lot
1:45:28of his guts are just on the right side
1:45:30and normally they're going to be spread
1:45:31without. So he's got some sort of
1:45:32intestinal rotation. Twisting of the
1:45:34bowel around the narrow mesenteric base.
1:45:36Genatreasia is common in neonates. Meals
1:45:40dverticulum has bleeding and
1:45:41obstruction. Stenosis causes chronic
1:45:44partial obstruction. Hersbrungs failure
1:45:46to pass mcconium. All right, so that's
1:45:48another practice question. My mic was
1:45:49off when I did it though. All right, for
1:45:51this next one, we're talking about
1:45:52phenol alanine elevation. So there's a 2
1:45:55week old male newborn found to have
1:45:57elevated serum phenol alanine. His
1:45:59parents follow a low phenol alanine
1:46:00formula strictly, but at 3 months he
1:46:02develops tremors. Port fails to be
1:46:04milestones. Which the following best
1:46:05explains his symptoms? The answer is
1:46:06defective metabolism of tetra
1:46:08tetrahydrobiopter. So he's got
1:46:10hyperphenol anemia with a neurological
1:46:13dysfunction even though he has dietary
1:46:14therapy. Phenylanine transporter defect
1:46:16that would impair the absorption but not
1:46:18cause the elevated levels. Lack of
1:46:19tyrosine would not cause the
1:46:20neurological defects you see branch
1:46:22chain and maple syrup not PKU homogenate
1:46:25oxidase deficiency is alopenura that
1:46:28have the dark urine. All right so
1:46:29there's your practice question. you
1:46:30can't metabolize phenol alanine and this
1:46:32is inherited in an autotoal recessive
1:46:34fashion and you would treat them by just
1:46:36giving BH4 because BH4 is the required
1:46:38co-actor for four phenol alanine
1:46:39hydroxilase also for tyroine hydroxilase
1:46:42and tryptophen hydroxilase it drives the
1:46:44synthesis of catakolamines and serotonin
1:46:46so if it's deficient then it'll cause
1:46:47increased in plusamine and serotonin
1:46:50decrease so you could have neuro
1:46:51findings despite a low malanine diet and
1:46:54you treat them with BH4 sapterin and
1:46:57also L-dopa carbodopa and five hydroxy
1:46:59tryptophen, but you should just look out
1:47:01for any positive newborn screens with
1:47:03high phenol alanine and worsening neuro
1:47:05symptoms on a low phenol alanine diet.
1:47:08Yep, there's the BH4 defect. All right,
1:47:10a study finds annual death rate from
1:47:12cardiovascular disease is 4.8 out of
1:47:1410,000 in diabetics and 2.1 out of
1:47:1710,000 in non-diabetics. The attributal
1:47:18risk is just this minus that. 4.8 minus
1:47:202.1 is 2.7. All right, the attributal
1:47:23risk, this is super easy. You just do
1:47:25that minus that and you're good to go.
1:47:27So, yep, the attributal risk. So RR is
1:47:29the relative risk and you just subtract
1:47:31them and you're good to go. It's super
1:47:32simple. All right, so now we're on 80.
1:47:34I'm going to keep working on optimizing
1:47:35the system so we can keep generating
1:47:36better images over here. But if you
1:47:39found this enjoyable or helpful, then
1:47:41like and subscribe. Hello everybody.
1:47:42Welcome back to MBME 29. Today we are
1:47:45going to be starting off strong.
1:47:47Question 81. These videos take several
1:47:49hours to make, so please be sure to like
1:47:50and subscribe. Also, I've been listening
1:47:52to your feedback. There's no green
1:47:53screen today, just my wonderful back
1:47:55room cuz that's what you guys decided on
1:47:56in the polls. And we'll start here with
1:47:58a practice question 81. A randomized
1:48:00control trial compares a new
1:48:01chemotherapeutic agent to standard care
1:48:04in patients with stage three colurectal
1:48:06cancer. After three years of follow-up,
1:48:08they report this data. The hazard ratio
1:48:09for recurrence in the new drug compared
1:48:11to the standard therapy is 72 and the
1:48:14confidence interval for 95% is between48
1:48:17and 1.16. So that 72 tells us that there
1:48:21is maybe some sort of a reduction
1:48:23recurrence. But this confidence interval
1:48:25means that it's not statistically
1:48:26significant. So the answer is C. There's
1:48:28no statistically significant difference
1:48:30in the recurrence between the groups. So
1:48:31the trick here is you have to determine
1:48:33if this contains one or not. And this
1:48:35one does contain one. And so you can't
1:48:37tell if it's going to be positive or
1:48:38negative. All right. So this next one is
1:48:40commonly seen in elderly women. So I've
1:48:42changed that photo. And our practice
1:48:43question is, a 68-year-old retired
1:48:46librarian presents with persistent upper
1:48:48back pain after reaching to a cupboard.
1:48:50She has a history of rheumatoid
1:48:51arthritis and has been on prednazone for
1:48:53the past four years. Physical
1:48:54examination reveals kyphosis. That's
1:48:57like the hunching of the back. And point
1:48:58tenderness over the thoracic spine. Ner
1:49:01exam is normal and dexa. Uh-oh. That's
1:49:02like an osteoporosis thing. Negative 2.9
1:49:04at the femoral neck. We've got serum
1:49:07calcium phosphate ALP and PTH within
1:49:09normal limits. What is the most likely
1:49:11finding? Well, she had her
1:49:13gluccocorticoid use and we see fragility
1:49:15and kyphosis and so there is a loss of
1:49:17the tbecular with preserved
1:49:19vanularization. So it's thinned out. So
1:49:21often times the patient will present
1:49:23with some sort of a condition like
1:49:25polymyalgramatica for which they're
1:49:27using chronic predinazone and
1:49:29gluccocorticoids actually accelerates
1:49:30bone reabsorption or you also might have
1:49:32a history of hypertension. Oftentimes in
1:49:34these patients, you'll have multiple
1:49:35vertebral compression fractures after
1:49:37they fall and then they'll be like,
1:49:39"Hey, here's a biopsy." And then they'll
1:49:40give you questions about that biopsy and
1:49:43you have normal mineralization. Whereas
1:49:45osteomacia and ricketetts is defective
1:49:47mineralization. So you have a wide
1:49:48osteoid. You should also look out for
1:49:50osteopetis. That's increased
1:49:52mineralization. It's thick scleretic
1:49:54bone, but it's also brittle.
1:49:56>> Brittle, that's petrosis. There's also
1:49:59page's disease of bone. And there you
1:50:00have thickened tbecula and also mosaic
1:50:03lamelar bone with a high turnover rate.
1:50:05And then cortical thickening is
1:50:06definitely not osteoporosis. It's more
1:50:08like paj. So that thinned tbecula that
1:50:11is osteoporosis especially of normal
1:50:14labs. Okay. So here's your explanation.
1:50:15So yeah look out for that silent bone
1:50:17loss gluccocorticoid induced
1:50:19osteoporosis. And the way to really
1:50:21think about this to bring this home is
1:50:22the bone has two major components. You
1:50:25have cortical bone and you have tbacular
1:50:26bone. So the cortical bone is super
1:50:28compact and that gives you your outer
1:50:30shell. The trabacular bone is really
1:50:32spongy and it's the inner lattice work
1:50:33especially inside the vertebrae and the
1:50:35hips. So trabacula is the thin little
1:50:37struts that distribute the forces and
1:50:39give you the strength. And in
1:50:41osteoporosis there's normal
1:50:42mineralization but there's just like
1:50:44less bone. And so osteoclast activity is
1:50:47greater than osteoblast activity. And so
1:50:49there's net bone reabsorption. So both
1:50:50tbacular and cortical bone are thin but
1:50:53the tbecular bone will go first because
1:50:55it has more surface area and a higher
1:50:56turnover and that's why thinned tbacula
1:50:59will show up on biopsy of osteoporosis
1:51:01because the tbcula are fewer and thinner
1:51:04and the cortex is also going to be
1:51:05pretty thin too but there's
1:51:07mineralization that's normal. So like
1:51:09the mineralization basically refers to
1:51:10the quality of the bone matrix and
1:51:12there's no wide osteoid seams or
1:51:15defective calcifications and so it's
1:51:16just osteoporosis because if there was
1:51:18defective mineralization that's called
1:51:20osteomacia basically that's where the
1:51:22osteoid is laid down but then it's not
1:51:24calcified so you get soft bone in
1:51:26osteomalacia. If it were increased
1:51:28mineralization then that's way too much
1:51:30mineral and the bone would be super
1:51:31dense but it's super brittle osteopetis
1:51:35and then thickened cortex tbacula that's
1:51:37page disease and that's chaotic
1:51:39remodeling and thick but structurally
1:51:40unsound. This next one we have a
1:51:4229-year-old woman presented to the
1:51:43neuroc clinic with complaints of
1:51:44persistent muscle weakness in her hands
1:51:46and trouble letting go of objects. So
1:51:48some muscle problems, progressive
1:51:50thinning of her hair and difficulty
1:51:51climbing stairs. She had cataract
1:51:53surgery at age 25. on exam percussion of
1:51:55the phenar eminence produces delayed re
1:51:57relaxation. Her mother reportedly had
1:51:59mild difficulty with speech as well in
1:52:01her later years. This is anticipation.
1:52:03So you're thinking okay trucleotide
1:52:05repeat disorders maybe myonic distrophe.
1:52:07Somebody in another chat mentioned hey
1:52:09do you have any videos on Huntington?
1:52:11Yes we do trucleotide repeat disorder
1:52:14video. Check that on the channel. But
1:52:15her younger brother also died of
1:52:16respiratory failure. So this is
1:52:17anticipation involving a repeat
1:52:19expansion of the non-enccoding DNA. This
1:52:22is mitonic distrophy type one G. C
1:52:25stands for cataracts, T stands for tupe
1:52:26and then the G stands for gonadyl
1:52:28atrophy or infertility and that's the
1:52:30triad and monic distrophe that you
1:52:32should know and that's how you link it
1:52:33up with cataracts tupe atrophy.
1:52:35Imprinting would be angel man prader
1:52:37willy chromosomal non-isjunction is
1:52:39tricome. The key to this one is just
1:52:41kind of recognizing what the condition
1:52:42is because of the cataracts the tupe the
1:52:44gonatal atrophy stuff. It could also be
1:52:46seen with myotonia that's like delayed
1:52:47relaxation after contraction. So and a
1:52:50good example of this is you can't
1:52:51release a handshake. You can't relax.
1:52:53Also hatchetface deformity. So that's
1:52:55like a lack of facial expression.
1:52:57Andythmias cardiammyopathy is like
1:52:58cardiac conduction defects. Anticipation
1:53:01is the problem here. Sarcomiric point
1:53:03mutation would be hypertrophic
1:53:04cardiammyopathy. So yeah watch for the
1:53:06grip myotonia early cataracts and
1:53:09cardiac complications. That's the cag
1:53:11kag triucleide repeat expansion autoomal
1:53:14dominant inheritance pattern. You see
1:53:15cororeia, athtosis, that's like
1:53:17dance-like movements and it also comes
1:53:19with cognition impairments like
1:53:21dementia, progressive cognitive decline,
1:53:22psychiatric stuff like depression,
1:53:24irritability, psychosis, and it's
1:53:25atrophy of the codate nucleus, decreased
1:53:28acetylcholine, and decreased GABA is the
1:53:30way that I like to remember that because
1:53:32C A stands for codate atrophy and
1:53:35decreased GABA because the codate
1:53:37nucleus is what's damaged. Whereas you
1:53:39contrast that with monic distrophe and
1:53:41that's we discussed cataracts toupe
1:53:44gonadatal problems. All right. Now the
1:53:46reason we have this photo up here is
1:53:48because you also might see you got like
1:53:49a young mother and this mom is having
1:53:51some of the symptoms or maybe the
1:53:53throughout the family you see symptoms
1:53:55of monic distrophe and then it's going
1:53:57to ask about the little kiddo and the
1:53:59little kiddo is already seeing those
1:54:01deformities and so you know it's going
1:54:03to be anticipation. So those trucleotide
1:54:06repeats are the problem. Hence my little
1:54:08photo there. Let me know in the comments
1:54:10where you would like me to be. If it's
1:54:11better if I hide the answer for a sec or
1:54:13something like that, I don't know. But
1:54:15the reason I have in this photo an
1:54:17elderly man is cuz you might be seeing
1:54:19this in somebody who's got some sort of
1:54:20a myioardial inffection. And this guy
1:54:22might have some sort of a respiratory
1:54:24problem. Let's say he's got like a
1:54:25bronco spasm. There's this thing that
1:54:27you need to be aware of called aspirin
1:54:29exacerbated respiratory disease. And
1:54:31that is due to cox inhibition and the
1:54:33shunting of arachidonic acid to the
1:54:35lucatrines. So, you're not going to give
1:54:37this guy aspirin, are you? No. Cuz he's
1:54:39got aspirin exacerbated problems. And
1:54:41so, you have to give him something else
1:54:43like an antiplatlet. All right. So, this
1:54:44is just one of the demographics you
1:54:46might see in this question. But now,
1:54:47let's dive into our question of a
1:54:4958-year-old woman who is admitted for
1:54:51unstable anga. She underos cardiac cath
1:54:53revealing 90% occlusion of the lad. A
1:54:56drug eluting stent is placed. History
1:54:59includes adult onset asthma and episodic
1:55:02wheezing. Aspirins withheld. What is the
1:55:05mechanism of the drug that's added? All
1:55:06right, you probably heard of clipadil
1:55:08the gr drugs. Clitadril the mechanism is
1:55:12it blocks the platelet ADP receptor and
1:55:14you get decreased ADP mediated
1:55:16activation of GP 2B3A receptors and
1:55:21those guys are going to cause decreased
1:55:23platelet aggregation and I like to
1:55:25remember aggregation because it's two
1:55:27and three which are the bigger numbers
1:55:29whereas adhesion with von willilibbran
1:55:31or glandsman is just the one which
1:55:33adhesion for some reason does not feel
1:55:35as numerous or as large as aggregation.
1:55:40So it's decreased aggregation due to
1:55:41clipidadril's inhibition of the ADP
1:55:44receptor. Now they might give you some
1:55:45trap answers and we'll look at some of
1:55:47these and I'll move myself out of the
1:55:48way. Now patients with aspirin
1:55:49intolerance are given ADP receptors to
1:55:52prevent aggregation. Thromben inhibition
1:55:54would be the gatrans not antiplatlets.
1:55:57Inhibiting cylo oxidase 1. That's
1:56:00literally the mechanism of action of
1:56:01aspirin. So you can't do that. Don't
1:56:04worry we won't give them aspirin. We'll
1:56:05give them cycle oxygenase one
1:56:07inhibitors. Same thing. inhibits direct
1:56:08activation of factor 10A. Well, that's
1:56:11the 10A in their name. I love that they
1:56:13did that by the way. XA, XA, and
1:56:16anti-coagulants, which are not your
1:56:17primary antiplatlets, and stimulating
1:56:19the process analoges. It's using
1:56:21pulmonary hypertension. They also might
1:56:23tell you other things for instance
1:56:24activating adenazine, diaminise. Well,
1:56:27zenazine actually inhibits platelet
1:56:29activity. So, that would be wrong.
1:56:30Doesn't have anything to do with
1:56:31serotonin either. Anything that inhibits
1:56:34gamma caroxilation is going to be
1:56:36warrin. And warin is not an antiplatlet.
1:56:38It's an anti-coagulant. And you might be
1:56:40saying, okay, well, what's the
1:56:41difference? Antiplat, anti-coagulant.
1:56:43Well, anti-platlets obviously work on
1:56:44the platelets. Examples are aspirin
1:56:46through the COX one 2 inhibition, which
1:56:49decreases TXA2, clipadrol, which
1:56:51literally blocks the ADP, MAB blocks
1:56:54GP2B3A, diritimal inhibits
1:56:56phosphodeststerase, increasing camp, and
1:56:58causes less platelet aggregation. Now,
1:57:00anti-coagulation drugs actually work on
1:57:03that whole cascade. So they inhibit the
1:57:04clotting factors and you use these for
1:57:07venus clots, DVTs, pulmonary ambisms,
1:57:09AIB and examples are Hepin, direct 10A
1:57:11inhibitors, direct thrombin inhibitors,
1:57:13warpherin, vitamin K dependent, gamma
1:57:16caroxilation of 27910, protein C and S.
1:57:19Don't you just love gamma? I think it's
1:57:21the third letter of the Greek alphabet.
1:57:23But yeah, so a big takeaway, arterial
1:57:25events like the MI and stroke, you need
1:57:27antiplatlets and then Venus events, you
1:57:29need anti-coagulant. And the reason why
1:57:31is these arterial clots they form in
1:57:33high sheer stress environments the
1:57:35arteries and so platelets dominate they
1:57:37adhere to the ruptured athoscotic plaque
1:57:40they're composed of plateletri stuff and
1:57:41it looks white so MI stroke
1:57:43anti-platelets that's why you need
1:57:45aspirin clipadril that stuff the venus
1:57:47stuff is the red red clots low flow low
1:57:50shear and coagulation cascade you have a
1:57:52fibbrin mesh and trapped red blood cells
1:57:54so it's really all about that sheer
1:57:55stress all right so postmiion stroke
1:57:57antipllets DVT pulmonary amalism aphib
1:58:00anti-coagulants, school beans. All
1:58:02right, for this question, we might see
1:58:04several different demographics, but here
1:58:05we have a middle-aged woman. And in our
1:58:07question, we have a 35-year-old man
1:58:09who's referred to by his employer due to
1:58:11concerns about his p persistent
1:58:13isolation and disengagement at work. He
1:58:15lives alone. He has no friends or
1:58:17significant relationships and says he
1:58:19prefers working the night shift because
1:58:20people are exhausting. This is clear.
1:58:22All right. Avoidance would be if he
1:58:24fears rejection. Odd beliefs and stuff
1:58:27is schizotypal. MD is not depressed and
1:58:30he's not narcissistic. So, that's kind
1:58:32of an easy breakdown there. That's kind
1:58:35of all there is to it. I don't want to
1:58:37take more time to explain something if
1:58:38it's a simple piece of logic that gets
1:58:40you there. Some other things you might
1:58:42need to look out for is they prefer
1:58:44solitary activities. There's a lack of
1:58:45desire for close relationships and
1:58:47restricted emotional expression.
1:58:49Schizoid. You should think schisvoid.
1:58:51Schisoid, the void of emotions,
1:58:53detached. All right. Now I'm giving you
1:58:55guys another example of a demographic
1:58:57you might see on test day for this
1:58:59condition. My goal is to help you think
1:59:01of a clinical scenario where sure in the
1:59:03question se it says 67y old man but you
1:59:07also might see a 65year-old woman. And
1:59:09in this question one of the key and most
1:59:11important factors is the smoking
1:59:13history. He's got a 45 packear history
1:59:16crackles dullness percussion the right
1:59:17lower lung field. Chest CT shows 5.2 2
1:59:21cm centrally located mass and the right
1:59:24main bronchus. Okay, so there's some
1:59:26really important points here and our
1:59:27answer is squamus cell but another one
1:59:29that I want you to think about is small
1:59:31cell. Now I put the explanation here on
1:59:33the screen for you to see. He's got
1:59:35pneumonia and hypercalcemia. Also
1:59:37anytime that you take keratin pearls,
1:59:38it's squamous cell. The tumor secretes
1:59:40PTHRP or parathyroid hormone related
1:59:43protein and that leads to hypercalcemia
1:59:46with low PTH. So it's like doing the job
1:59:49of PTH but it's like an imposttor that's
1:59:51squamous cell for you. Now why is it not
1:59:52small cell? Well what I wanted you guys
1:59:55to know is that small cell is also
1:59:57central and that one would show
1:59:58neuroindocrine markers not the keratin
2:00:00pearls and you'd have rapid growth and
2:00:01early metastasis. So a good answer
2:00:03choice because it's central large is
2:00:05peripheral and that's how I want you to
2:00:06think about it. Just be like large
2:00:08peripheral done a carcinoid tumor would
2:00:10have very differentiated neuroendocrine
2:00:11cells and chromogren a positive stained
2:00:14adnocarcinoma is peripheral. So guys,
2:00:17the easiest way to do this, I promise,
2:00:18is just think peripheral versus central.
2:00:21And how do you know it's central? What
2:00:22has an S sound? Central
2:00:26cell, small cell, S sound, central.
2:00:29That's the way to think about it. It's
2:00:30the easiest way, I promise. Adeno
2:00:32peripheral, large peripheral. So you
2:00:33cross them out immediately. And then
2:00:34carcoid tumor, neuroendocrine,
2:00:36chromogran is what should come to mind
2:00:38with carcinoid. But yeah, so speaking of
2:00:40other demographics, you might find it
2:00:42could be an elderly woman. She's a
2:00:44smoker, right? She's got just been
2:00:45smoking her whole entire life and maybe
2:00:48she's got some fever, some coughing,
2:00:49hemopasis, but the finding is going to
2:00:51have to be a right or left middle lobe
2:00:54consolidation, a hiler mass. So like a
2:00:56central lesion. So squamous cell, small
2:00:59cell and then adno and bronco aviola
2:01:02carcinoma and large cell that stuff
2:01:04that's peripheral but squamus and small
2:01:05is central and central. You need to know
2:01:07that and then you have to know
2:01:08parathyroid hormone like protein is
2:01:11related to squamus whereas the small
2:01:13cell has all other sorts of goo
2:01:15associated with it act sih
2:01:18neuroindocrine goo
2:01:23myself up I don't know why but yeah adno
2:01:26what's there to say about adno it's the
2:01:28most common overall especially in
2:01:30non-smokers in fact here don't smoke
2:01:33guys because if you go to your doctor's
2:01:34office they're going to be like do you
2:01:35smoke and If you don't smoke, you're
2:01:37probably not going to have squamous cell
2:01:38carcinoma, right? So, you're saving
2:01:40yourself a whole form of cancer just by
2:01:42not smoking. So, please don't do it to
2:01:43yourself. Unless you have ambitions to
2:01:45take over Europe or conquer Ukraine or
2:01:47some other territory, in which case,
2:01:48smoke all you want. I digress. I'm just
2:01:50trying to think like what advice would I
2:01:51give to young Hitler. I'd probably be
2:01:52like, "Yeah, smoke all you want, man."
2:01:54Okay, I should probably just stop this
2:01:55train of thought right now. Anyways,
2:01:56adnocarcinoma is the most common lung
2:01:58cancer overall. large cell carcinoma
2:02:00undifferiated often peripheral it's
2:02:02super aggressive that's large cell and
2:02:04like lymphas those can involve the hiler
2:02:06nodes but you'd have like systemic B
2:02:09symptoms are you familiar with the B
2:02:10symptoms like night sweats weight loss
2:02:11lympadnopathy all that stuff but smoking
2:02:14really makes the primary lung cancer
2:02:15diagnosis a lot more likely than like a
2:02:17lymphoma so yeah squamus cell central
2:02:19lung cancer strongly associated with
2:02:21smoking can cause bronchial obstruction
2:02:23as well and that could lead to things
2:02:24like post-obstructive pneumonia but omg
2:02:27what's post-obstructive pneumonia Well,
2:02:29that's an infection that develops in the
2:02:30lung tissue distal to the blocked
2:02:33airway. So, it's usually a tumor, but it
2:02:35could be something else, a structure for
2:02:36body. By the way, I have trained an AI
2:02:39model on everything you need to know for
2:02:40step one using widely available step one
2:02:42materials. And so, all of these
2:02:44explanations are going to be
2:02:45deliberately curated so that they are
2:02:47high yield for you. And I'd be happy to
2:02:48go into that in another video. But the
2:02:51resources that you're seeing here, I'm
2:02:52not just saying airway obstruction for
2:02:54no reason or distal infection stuff. The
2:02:56only reason you're getting this these
2:02:57associations central lung cancers
2:03:00squamus and small because they are
2:03:01important and will be tested on step
2:03:03one. I'll never tell you anything
2:03:04besides my random funny aides and memes
2:03:06that it's not high yield for step one.
2:03:08At least that's my goal. And please call
2:03:09me out on that and give me feedback. I
2:03:11love the feedback. All right, moving on.
2:03:13The big clue for the exam is pneumonia
2:03:14that keeps recurring in the same exact
2:03:16location over and over again. Definitely
2:03:18think post-obstructive pneumonia. So you
2:03:19might see in the proximal right middle
2:03:21lobe bronus. So you get that pooling and
2:03:23the post obstructive pneumonia right
2:03:25there. All right, leaving the
2:03:26explanations on the screen for a second
2:03:27there for you. All right, question 86.
2:03:29We got a researcher. This is you. We're
2:03:31studying nerve regeneration in lab rats.
2:03:34Group A receives a crush injury to the
2:03:36sciatic nerve and group B has the optic
2:03:38nerve. So already what's coming to mind?
2:03:40Sciatic peripheral optic central. At the
2:03:42end of the study, histoologgical
2:03:44examination reveals robust external
2:03:45regrowth and remination in group A.
2:03:48That's cuz it's peripheral but no
2:03:50regeneration in B. What best explains
2:03:52this is the exonal regrowth is inhibited
2:03:55by the CNS gal derived proteins. So the
2:03:57optic nerve is part of the central
2:04:00nervous system and it's mileelinated by
2:04:01what? Oligodendrittes
2:04:03and those guys release inhibitory
2:04:05molecules. You don't need to know those
2:04:06but like no go a mag all that stuff and
2:04:09they block axonal regeneration.
2:04:11Basically some nerves regenerate and
2:04:13some can't. CNS axons will fail to
2:04:16regenerate every single time. You might
2:04:18say, "Oh, well, the optic cayazm is
2:04:20crossing." But who cares? The axons
2:04:22can't regenerate long before that. So,
2:04:24it's not anything to do with neural
2:04:25crest cells either. The PNS peripheral
2:04:28nervous system neurons and ganglia are
2:04:29neural crust derived. But the optic
2:04:31nerve is CNS. It's from the dianphylon,
2:04:34the neural tube. So, kind of different
2:04:36embryological origin there. And it's
2:04:38pretty much all there is for this one.
2:04:40CNS axons don't regenerate because
2:04:43they're mileelinated by ilodendrites
2:04:45which release inhibitory factors unlike
2:04:47swan cells in the peripheral nervous
2:04:49system that can promote regrowth. And
2:04:51you guys might be wondering, okay, why
2:04:52though? From an evolutionary
2:04:53perspective, doesn't make sense to just
2:04:54always be able to regrow. For my
2:04:56undergrad at Harvard, I studied
2:04:57evolutionary biology and happen to know
2:04:58a little bit about this. Basically,
2:05:00evolution has decided stability should
2:05:02be prioritized over regrowth for the
2:05:05central nervous system. Think about the
2:05:06peripheral nervous system, right? You
2:05:07need to regrow it. You get your limb
2:05:09chopped off. Ouch. You get it crushed,
2:05:10right? A crush entry. We have to regain
2:05:12the movement of our periphery, right?
2:05:14So, the swan cells go to the rescue. But
2:05:15the CNS, there you have tons of billions
2:05:18of connected neurons. And if you regrow
2:05:20them, uh-oh, all of a sudden, my
2:05:22eyeballs connected to my elbow. Not
2:05:24good. You could even get hallucinations,
2:05:26seizures, all that stuff. And so, yes,
2:05:28if there were some divine technician
2:05:30that could come down and rewire you,
2:05:32then yes, it's a great idea to regrow
2:05:34them. But in an evolutionary landscape
2:05:36that's prone to mistakes, miswiring,
2:05:39aberant circuits, and wasted energy on
2:05:41inaccurate repair can all take place.
2:05:43And so, Aiththoth
2:05:45or whatever, whoever made you, random
2:05:48chance by natural selection, has decided
2:05:50it's in your best interest not even to
2:05:51mess with that. So, that's the
2:05:52evolutionary mechanism behind CNS and
2:05:54PNS design trade-offs. Cool beans. Okay,
2:05:56there's the explanation for you. All
2:05:58right. And it's all about the
2:05:59mileination patterns, right? Myination
2:06:00patterns, the inhibitory proteins of the
2:06:02CNS. So you learn something new every
2:06:04day. Kind of fun, kind of quirky, kind
2:06:05of cool. All right. The demographic that
2:06:07you might see in the next question could
2:06:08be man, woman, elderly. Basically, what
2:06:11USML was trying to do for this topic at
2:06:13least is they're trying to say, "Hey,
2:06:16how could we get somebody in a
2:06:17demographic for colon cancer?" And so
2:06:18that's why I've given you this woman up
2:06:20here who meets that criteria, maybe. So,
2:06:22in our question that I've made myself,
2:06:24we have a 66-year-old man presenting
2:06:27with progressive fatigue, vague
2:06:28abdominal discomfort, decreased appetite
2:06:30over the last 4 months, dark stools,
2:06:32unintentional weight loss, so cancer.
2:06:34Oh, wow. 50-year smoker and alcohol
2:06:36consumption. Hemoglobin is eight,
2:06:38heatrate 26. Look at that mean
2:06:41corpuscular volume. Normal estp
2:06:44plate count is crazy high. Which organ
2:06:47is most like involved in the metastatic
2:06:49spread? Okay, so the answer is the liver
2:06:51and let's talk about why. Our labs show
2:06:53us colonic adnocarcinoma and colon
2:06:55cancer most often metastasizes first to
2:06:58the liver. And how does it do that?
2:07:00Well, there's this awesome thing called
2:07:02the portal venus system and GI blood
2:07:04will drain and you'll go from the
2:07:06superior inferior mesenteric veins to
2:07:08the portal vein to the liver. And so the
2:07:10colon cancer can metastasize and the
2:07:12liver will get that metastasis. So the
2:07:14liver metastasis is more common than
2:07:16primary liver tumors like for instance
2:07:19hepatoscellular carcinoma. It's even
2:07:21more common than that right now. Why is
2:07:23it not the brain? That's the site for
2:07:25lung melanoma and renal metastasis. Why
2:07:27not the lungs? That's common for
2:07:29sarcomomas and renal but colurectyl
2:07:31drains from the liver. Skin metastasis
2:07:33is rare seen in melanoma and breast. And
2:07:35then the bone typical prostate, breast
2:07:37and lung. So basically the hard part
2:07:39about this question is the liver is the
2:07:41most common site for metastasis of the
2:07:43GI cancers and the the reason why I'll
2:07:46explain here. So blood from the colon
2:07:49and the rectum drains into the SMV
2:07:52drains the right colon the IMV drains
2:07:54the left and they both join the portal
2:07:56vein to the liver. So basically all
2:07:58these tumor cells are going to be
2:07:59shedding in the venus blood and going
2:08:00straight to the liver. It's the first
2:08:02pass filter. The liver obviously has a
2:08:04huge blood supply, 25% of your cardiac
2:08:06output and it's got some leaky stuff to
2:08:07it. The penetrated sinosoids and you've
2:08:10got some growth factors there and so
2:08:11it's really good for tumor growth. Now
2:08:13lung cancer spreads to the brain,
2:08:15adrenal and bone, right? Because there
2:08:17we have systemic venus return to the
2:08:19rest of the systemic circulation.
2:08:21Prostate and breast, there you have bone
2:08:23metastasis that's common just because
2:08:24the micro environment there is really
2:08:25nice for it. And melanoma can spread
2:08:27everywhere, skin, brain, liver, lung.
2:08:29But how do you know that granny has
2:08:31cancer? Well, I told you about the age,
2:08:33right? So, we had cancer risk at that
2:08:35age. Anyways, then there's
2:08:36constitutional symptoms, right? We get
2:08:37the the weight loss. There's also GI
2:08:39symptoms, the chronic constipation,
2:08:40maybe you'll see. And you could even
2:08:42inspect it and they'll show like some
2:08:43sort of a mass and it'll be like a firm
2:08:45rectal mass. But also look at that MCV,
2:08:47right? Check out also look at this MCV.
2:08:50Now, in elderly adults, this is iron
2:08:52deficiency anemia until it's proven
2:08:54otherwise. So, in this setting, the
2:08:55occult blood loss is from a colctal
2:08:58tumor, right? That's the the number one
2:09:00cause. And if it were gynecological in
2:09:01nature then you wouldn't find the rectal
2:09:03wall tumor either. If it's hematlogic
2:09:05like think like a lymphoma for instance
2:09:07then the mass would not localize so
2:09:08clearly to the rectum and the labs would
2:09:10be a little bit different too. So you
2:09:11see rectal colonic mass iron deficiency
2:09:13anemia and weight loss that's that's
2:09:15colonic you know and then you think the
2:09:17number one metastasite is the liver. So
2:09:19that's the answer. All right look I
2:09:20found a picture of you on the web. A
2:09:22research team is developing novel
2:09:24vaccine against mafu influenza type B
2:09:26using capsular polyaccharides to enhance
2:09:28immunogenicity. They're testing several
2:09:29conjugation strategies in mice. One
2:09:31formulation combines polysaccharides
2:09:32with bacterial protein recognized by
2:09:34tolike receptor 5. What's the outcome of
2:09:36this approach? Well, the answer is
2:09:37increased switching to IGG via T
2:09:41dependent activation. Now, the problem
2:09:43here is that polysaccharides like nicer
2:09:46menitis or rather the capsule that they
2:09:48possess by themselves will have T-C cell
2:09:50independent antigens. So, they activate
2:09:52the B cells directly, but the response
2:09:55is mostly IGM, right? that's shortlived.
2:09:58There's no memory of it. So to get IGG
2:10:01class switching in memory, you need T-
2:10:03cell help. So how do we get those T-
2:10:04cells in there? Well, we're going to
2:10:06conjugate the polysaccharide to a
2:10:07protein carrier. And the question is,
2:10:09which protein carrier are we going to
2:10:10use? Well, we want something that's
2:10:12strong amogenic. We want something that
2:10:14activates antigen presenting cells and
2:10:16something that stimulates T- helpper
2:10:17cells because that will promote B cell
2:10:19class switching to get that stronger
2:10:21response. And so we conjugate it to
2:10:23fleellin to like receptor 5 liand
2:10:25provides T- cell dependent antigen
2:10:27presentation and innate immune
2:10:29stimulation. It promotes the class
2:10:31switching memory B cell formation and
2:10:32higher titers. It's perfect. Enhanced
2:10:34IgA is mucosal. IgA is good for that.
2:10:37But we're targeting the IGG. Cytotoxic
2:10:39Tlymphosytes. Cytotoxic 8. Think MHC1.
2:10:44So polyaccharides don't enter the
2:10:45systolic oh cytoolic pathway needed for
2:10:48CD8 positive T- cell activation and
2:10:50immune tolerance repeat exposure without
2:10:53co- stimulation that's when you should
2:10:54think of tolerance and antibodies
2:10:56without T- cell involvement why would
2:10:57you need that that's what we're trying
2:10:59to solve so it would be E and yeah so
2:11:01basically these these pure
2:11:03polysaccharide vaccines like those that
2:11:05are used against meninja caucus they
2:11:07don't work very well in infants and
2:11:09that's because they only trigger a very
2:11:10weak IGM response with no memory but if
2:11:12you had a flegillan And then the whole
2:11:14thing will be treated like it's a
2:11:15protein antigen. And now if it's a
2:11:17protein antigen, the B cells can be
2:11:18like, "Oh my gosh, let me show this to
2:11:19my MHC2 buddies." And then the T-H
2:11:22helpper cells are going to be like, "Oh
2:11:23my gosh, let's do a helper response. Oh
2:11:25my gosh, let's make IG." And that's how
2:11:27we get that reaction. And to receptor 5,
2:11:29that's just icing on the cake. It's not
2:11:31going to be other stuff like
2:11:32dinotropenol. That's a toxic
2:11:34mitochondri. You wouldn't just use like
2:11:36a sugar cuz sugars will just stabilize
2:11:38things. And lipopolysaccharides are
2:11:40amunogenic, but they're too toxic and
2:11:43they can share sometimes they can share
2:11:45epitopes with host cells. So you would
2:11:46not necessarily want to use a
2:11:48lipopolyaccharide. Pulmitic acid is just
2:11:50like a common, you know, lactic acid or
2:11:52fatty acid. Those aren't immunogenic. So
2:11:55yeah, just look out for something
2:11:56amogenic, something that would help with
2:11:58the situation with the TLR5 liand
2:12:01causing the T- cell dependent reaction
2:12:03and flugglen's perfect for that. You get
2:12:04class switching, memory formation, and
2:12:06all that good stuff. Now this next
2:12:08demographic is probably going to be
2:12:09elderly. It could be a man or a woman
2:12:11for instance like what we see up here
2:12:13who just falls. They could have an
2:12:14interotro cancer fracture something like
2:12:16that. And the problem is they've got
2:12:18their like a shortened externally
2:12:19rotated leg or some sort of a hip
2:12:21fracture. And there's a pneumonic that's
2:12:23super helpful for this. P go Q.
2:12:26P stands for purformis. G is the
2:12:30superior. O stands for opterator. G is
2:12:32another one of the jamalises. I think
2:12:33it's like jamalis inferior. O is also
2:12:36the opterator but this one's the
2:12:37externis and this one's the internus. So
2:12:40it's the opterator jamlis jamlis
2:12:42opterator. So go o gq is a quadratus
2:12:46feorous. Okay. So p goq
2:12:50that's the pneumonic and those are the
2:12:52lateral rotator groups and they all
2:12:54insert around the greater trocanter and
2:12:56they're the prime movers for lateral
2:12:58rotation. So here we have a 60-year-old
2:13:00man difficulty walking left hip pain
2:13:02after slipping while getting out of the
2:13:03bathtub. His left leg is shortened, lies
2:13:06externally rotated compared to the
2:13:08right. What contributes to the external
2:13:09rotation of the thigh and maybe impaired
2:13:11opt.
2:13:14And that's all there is to it. Glutius
2:13:15medius is abduction because usually
2:13:17people say maximus and it's abnormal if
2:13:19you say medius. That's how I remember
2:13:21it. Sartorius, Taylor's muscle, hip
2:13:23flexion and knee flexion. Vasis
2:13:25lateralis, knee extension, adductor
2:13:27longus. Well, adduction. So, yep.
2:13:29Fractured hip. It'll rotate your entire
2:13:31leg out like it's a broken hinge. All
2:13:33right. An extra demographic is going to
2:13:34be some young boy or young girl. In this
2:13:37case, we have a young girl is brought to
2:13:38the clinic after collapsing during a
2:13:40school choir rehearsal. She has no prior
2:13:43medical history, but has required
2:13:45hearing aids since infancy. On exam,
2:13:48she's alerted with normal vitals. Her
2:13:49ECG shows a QT interval of 520. Genetic
2:13:53testing reveals mutation in a gene
2:13:54involved in cardiac repolarization,
2:13:56which the following best describes
2:13:58mutated protein. All right, this is Jeal
2:14:01Lange Nielson syndrome. It's congenital
2:14:03long QT syndrome caused by mutations of
2:14:05the voltage gated potassium channel. So
2:14:07here's our explanation and you might be
2:14:09wondering why is it potassium? Well,
2:14:11normal cardiac repolarization has
2:14:12outward potassium currents and if the
2:14:15potassium channel function is defective
2:14:16then it's delayed repolarization and
2:14:18delayed repolarization has a longer QT
2:14:21interval. And so the prolongation
2:14:23predisposes towards sod to point syncopy
2:14:25or sudden death. And what's with the
2:14:27deafness, right? The inner ear cells
2:14:28also rely on potassium channels. So
2:14:30that's what's interesting about this
2:14:31condition and they recycle the potassium
2:14:33to the endolymph which is you know just
2:14:35like the fluid in the membranous
2:14:36labyrinth of the ear and there's
2:14:37dysfunction there right so you have
2:14:38congenital sensory neural hearing loss
2:14:40and is automal recessive where you have
2:14:41the cardiac problems and you also have
2:14:43the ear problems there's also another
2:14:45variant of this that's called romano
2:14:46ward which is automal dominant and
2:14:48that's only involving the cardiac
2:14:49there's no like hearing loss with that
2:14:50one and they're going to try to get you
2:14:51with all sorts of answers for this one
2:14:53they could ask about neurotransmitter
2:14:56calcium for instance and that can be
2:14:58implicated in like ep epilepsies and
2:15:00some arrhythmias but definitely not long
2:15:03QT syndrome. They could try to get you
2:15:05talking abouturgic receptors you know
2:15:07that would be the parasympathetic
2:15:09slowing of the heart rate and that's
2:15:10just not related to QT stuff. They'll
2:15:12get you about like gap junctions that's
2:15:14involved in propagation not
2:15:16repolarization and it's not betadinurgic
2:15:18because that could exacerbate it but the
2:15:20receptor is not mutated. All right so
2:15:22there you go. Hopefully this has been
2:15:23helpful. These are 10 more questions. If
2:15:25it was like and subscribe let me know
2:15:27how I can improve. Do you guys like this
2:15:29demographic image for each question?
2:15:31Would you like for it to pertain exactly
2:15:33to this question or just general
2:15:34demographics so that I can generalize
2:15:35these questions better and open up the
2:15:37conversation that way? Let me know what
2:15:38you think and we'll see you guys in the
2:15:40next video. Hello everybody. Today we're
2:15:42going to be continuing with NVMe 29.
2:15:44This takes so many hours of work. If
2:15:47you're benefiting from this, please like
2:15:48and subscribe. My goal is to help you
2:15:50pass step one. Here we go. In our first
2:15:52question, we have a 60-year-old man
2:15:53comes to the emergency department due to
2:15:54hematis. reports progressive fatigue and
2:15:57early satity. He has history of alcohol
2:15:59use disorder. On examination, he has
2:16:00distended abdomen and shifting dullness
2:16:02with multiple spider angata on his
2:16:05chest. Lab studies show mild
2:16:07thrombocyopenia and hypoendoscopy
2:16:09reveals prominent gastric varies.
2:16:11Imaging shows spleenomegaly and anodular
2:16:14liver. Increased venus pressure and
2:16:15which of the following vessels is most
2:16:16directly responsible for the formation
2:16:18of gastric veraces. So here the answer
2:16:20choices and the answer is indeed the
2:16:21left gastric vein. And they can ask this
2:16:23several ways. middle-aged older man,
2:16:25he's going to have alcohol use. That's
2:16:27guaranteed, right? Why alcohol use?
2:16:29Because that increases the risk of
2:16:31cerosis. And on exam, you see the spider
2:16:33angular
2:16:34liver stuff. That means cerosis. That's
2:16:37step one's way of being like, dude, this
2:16:38this guy has a seros liver. And on CT,
2:16:40you see like a mass in the liver.
2:16:42Anytime you have a mass in the liver,
2:16:43what does that mean? Well, that's going
2:16:45to be a possible hpatoscellular
2:16:47carcinoma, which is also commonly seen
2:16:48in serotics. And so they'll ask hey like
2:16:51which vein is going to be developing the
2:16:52hypertension due to this cerosis. So in
2:16:54order to answer this question we have to
2:16:56know a little bit about the portal venus
2:16:58anatomy. Let's just call this your liver
2:17:00right here and plug it into this liver.
2:17:02We have got a portal vein kind of
2:17:04running along like that. So yeah that's
2:17:05our portal vein. And again this big
2:17:07thing right here this is the liver.
2:17:08Here's like our portal vein. Going off
2:17:10of that you can have this which is known
2:17:12as the left gastric vein. And of course
2:17:14this right here is our pancreas which
2:17:16makes this right here the superior
2:17:18mesenteric vein. Then you have you know
2:17:19like your middle collic, your right
2:17:21collic, juno ilial veins. Here's your
2:17:23inferior mesenteric vein and of course
2:17:25your splenic vein which takes you out to
2:17:27your spleen. But right here that right
2:17:29here is the left gastric vein. And so
2:17:31the portal vein is formed by the splenic
2:17:33vein, superior mesenteric vein right
2:17:35there. So those are splenic vein,
2:17:37superior mesenteric vein and the left
2:17:39gastric vein right there. That's what
2:17:41forms it. And these tributaries include
2:17:43the short gastric veins, right? Those
2:17:45drain into the splenic vein. Anything
2:17:47draining into the portal vein is going
2:17:49to be subject to portal hypertension.
2:17:51And that's because this big old liver
2:17:53right here is serotic. How do we know
2:17:55it's serotic? Because he's an alcoholic.
2:17:57And also because of spiderjimata and
2:17:59hard nodular liver. Also the mass tells
2:18:02us hpatoscellular carcinoma. And a
2:18:04common cause of hpatosular carcinoma is
2:18:06cerosis. And so they're they're going to
2:18:08try to trick you in various ways. They
2:18:09might say like, oh, the hpatic vein.
2:18:12Well, that drains out of the liver into
2:18:14the IVC. And so that's a little more
2:18:16like budari syndrome, the hpatic vein
2:18:18thrombosis, not cerosis. All right, so
2:18:20they might try to trick you like that.
2:18:22In our answer right here, we know the
2:18:24left gastric vein drains both the lesser
2:18:26curvature of the stomach and the lower
2:18:27esophagus. In portal hypertension,
2:18:29increased resistance causes the backup
2:18:31there causing those varices. Short
2:18:33gastric varices which also contribute to
2:18:35gastric veraces drains this blank vein
2:18:37which joins the portal vein. The left
2:18:39renal vein would be nutcracker syndrome.
2:18:41Hpatic vein is as we mentioned budari
2:18:43syndrome. Right? Superrenal drains the
2:18:45adrenal gland and inferior frenic drains
2:18:47the diaphragm. So if they try to get you
2:18:49on like renal vein then you should say
2:18:51no that's not the answer. Why? Because
2:18:52that drains the kidney into the IVC. One
2:18:56thing we do know is that this short
2:18:57gastric vein that drains into the
2:18:59splenic and the portal vein and that's
2:19:01affected in portal hypertension. And so
2:19:02you get the high pressure right there.
2:19:04All right. For question 92 I wrote down
2:19:06the word infusion because that's the
2:19:08most important part of this question. We
2:19:09have a 22-year-old female who collapses
2:19:11after a marathon. And look at that.
2:19:13Blood pressure super low. Neck veins are
2:19:14flat. But then we give her isotonic
2:19:16saline and the heart rate drops to 92.
2:19:19Blood pressure improves to 105. What
2:19:21best describes the new hemodynamic state
2:19:24on the graph showing cardiac and
2:19:25vascular curves? Well, it's going to be
2:19:27the same cardiac function curve, but the
2:19:29vascular function curve is shifted to
2:19:31the right. Now, in our question, we have
2:19:32a 22-year-old female, but you can also
2:19:34have a male as well. Totally fine
2:19:36demographic wise. Basically, we have a
2:19:38young trauma patient with large blood
2:19:40loss and hypoalmic shock. The findings
2:19:42then would be tacicardia, hypotension
2:19:44and lacerations with hemorrhage. Right?
2:19:46That's typically how this could present
2:19:48or they could just be dehydrated. And
2:19:49then for management, you give them a
2:19:51rapid infusion. You do volume
2:19:52resuscitation. And what happens in
2:19:54hypoalmia is you have a decreased
2:19:56preload. Right? That's the right atrial
2:19:59pressure. And you also have a decreased
2:20:01stroke volume and cardiac output. And so
2:20:03the body, how is that going to
2:20:04compensate? Well, the body's going to
2:20:05compensate with increasing your heart
2:20:07rate, increasing your arterial
2:20:09constriction, systemic vascular
2:20:11resistance. But whenever you give
2:20:12fluids, you're increasing the blood
2:20:14volume, right? So, you're increasing the
2:20:15mean systemic filling pressure. And on
2:20:18that vascular function curve, it's going
2:20:19to shift it to the right since the Venus
2:20:22return improves at any given right
2:20:25atrial pressure. So, it's like we have
2:20:26your cardiac output here, you have your
2:20:28central venus pressure right here. And
2:20:30it's like this on the continuum. You
2:20:31start here, you end up here. You go
2:20:33higher in both. The contractility does
2:20:35not change though, right? You got a
2:20:36healthy heart. There are no inotropes
2:20:37that are given. So the curve is going to
2:20:39stay on that exact same line, but the
2:20:41new intersection point is going to move
2:20:42up along the cardiac curve. So you have
2:20:44a higher right atrial pressure. Why do
2:20:46you have a higher right atrial pressure?
2:20:47More preload. There's also higher
2:20:49cardiac output, right? That's the Frank
2:20:51Starling mechanism. And there's no
2:20:52change in the contractility. And so
2:20:54you're just going to be on that same
2:20:56kind of curve line, but the pressure
2:20:58increased and the cardiac output also
2:21:00increased as well. and it's increased
2:21:01because of the Frank Starley mechanism,
2:21:03right? The contractility being lowered
2:21:05would be like if you if you were on a
2:21:07different line. So basically the the
2:21:09high yield takeaway here is that fluids
2:21:11cause a rightward shift of the vascular
2:21:13function. Inotropes cause an upward
2:21:15shift of the cardiac function curve.
2:21:17Venodilators cause a leftward shift of
2:21:19the vascular curve and hemorrhages cause
2:21:21a leftward shift as well on the vascular
2:21:24curve. All right, so that's the high
2:21:25yield takeaway for this graph. Okay,
2:21:28next we have a 24 year old woman. It
2:21:30could also be a young man as well. So we
2:21:33have both represented in the
2:21:34demographics. Presenting with painful
2:21:36swelling of her left forearm 3 days
2:21:38after scraping in our rock climb. Exam
2:21:40shows arythemma warmth and pilent
2:21:42drainage from the 2 cm area. Biopsy
2:21:44reveals an abundant neutrfil and
2:21:47adjacent vascule but limited
2:21:49infiltration into the tissues. Further
2:21:51analysis shows reduced endothelial
2:21:53expression of a molecule normally
2:21:55upregulated by TNF alpha and IL1 to
2:21:57mediate luccoy rolling. Which of the
2:21:59following molecules is deficient? All
2:22:01right. So those are the answers. Now
2:22:03what I want to teach about this question
2:22:04is you might have all sorts of things.
2:22:07An infection and an abscess from a
2:22:09splinter right and what's happening is
2:22:11we have neutrfils and also other
2:22:13lucasytes. They have to leave the
2:22:14bloodstream and enter into the tissue.
2:22:16Right? And by the way a neutrfilic is
2:22:17just something that is stained by
2:22:19neutral dyes. That's why they call it
2:22:20neutrfilic. These are the white blood
2:22:22cells that are important in the immune
2:22:24system that help to fight your body's
2:22:25infections. And usually you have
2:22:26neutrfilia in infections, inflammation
2:22:28and other neoplastic processes. So like
2:22:31you know cancers can cause them. Think
2:22:33like chronic myoid leukemia as well.
2:22:35Tumors can cause this. Basically they
2:22:37are the key components of the immune
2:22:38system, the first responders to
2:22:40infection, inflammation. But you can
2:22:41also see them elevated in cancer and due
2:22:43to stress reactions and certain
2:22:44medications. So they're elevated in a
2:22:46whole lot of things. So basically our
2:22:48neutrfils and our lucasytes leave the
2:22:50bloodstream. They have to enter the
2:22:51tissue. And this question is essentially
2:22:53asking which adhesion molecule first
2:22:55tethers the lucasytes to the
2:22:57endothelium. So we have to know the
2:22:59lucasite extravisation sequence. It's
2:23:01super super testable. I've drawn this a
2:23:03couple times but first is margination
2:23:05and rolling. And there we have the
2:23:07selectants. So you have e selectin p
2:23:09selectin on the endothelium and it binds
2:23:12lewis on the lucasytes and that way it
2:23:15can roll along the vessel wall. So if
2:23:16you know that you know this answer and
2:23:18you got it. tight adhesions is the ICAM
2:23:20the VCAM those bind the integrants and
2:23:23there you think LFA1 MAC1 VA4 on the
2:23:26lucasytes that's the ICAM the adhesion
2:23:29then you have transmigration also known
2:23:31as diipides that happens with PCAM
2:23:33that's CD31 which if you guys know my
2:23:35PEG system is MAT and so I imagine him
2:23:37rolling out a mat and then just passing
2:23:39right on through the endothelial cells
2:23:40cuz that's what diabetesis like trans
2:23:42migration is and then we have last one
2:23:44is the migration to the actual site and
2:23:46that's the chemotaxis And chemotaxis is
2:23:49directed by IL8. Also C5A, they love
2:23:52that one for some reason. LTB4 and
2:23:54Calocrine is the last one that they'd
2:23:56ever ask you about. All right, so those
2:23:57are the steps. So we know our answer is
2:23:59selectant. And they could ask you all
2:24:01sorts of things. Here are some examples.
2:24:03The integrants from adhesion not
2:24:05rolling. You're integrating collagen
2:24:07structural not involved in the
2:24:08recruitment stuff. Caderins are the cell
2:24:11junctions non-immune stuff. Matrix metal
2:24:13proteines degrade ECM. So yes, this is
2:24:16essentially a question about the
2:24:17molecular velcro. It slows down the
2:24:18white blood cells before they fight the
2:24:20infections. You have to know that's the
2:24:21selectins. Cadherins, they help with the
2:24:23adhesion between epithelial. So like the
2:24:25zonadherins, desmosomes, that's more of
2:24:27the caderin job. So it's not the right
2:24:29answer. Extracellular extracellular
2:24:32matrix proteins. That's like the
2:24:33collagen, fibonnectin, laminin. That's
2:24:36scaffolding. All right, we're not
2:24:37talking about the scaffolding here.
2:24:38We're talking about the selectins, the
2:24:39velcro that helps the lucasytes come on
2:24:42in and stay there. G- proteins are for
2:24:44intracellular signaling. So, yep, we're
2:24:46talking about the rolling step, the
2:24:48rolling phase. All right, here we have a
2:24:5028-year-old woman found being stranded
2:24:52in the mountains for 6 days. So, you can
2:24:54see there are also other demographics it
2:24:56could be. Here's a man. He's also been
2:24:58stranded. Access to melted snow, but
2:25:00there's no food. So, she's got water,
2:25:02but no food. Which of the following
2:25:03changes is most likely occurring? Well,
2:25:05I've taken some notes here. We have
2:25:07water, we have no food. That means that
2:25:09means that we are in a starving state,
2:25:11right? So, we're well past the glycogen
2:25:13depletion because the glycogen stores
2:25:15are usually gone after like 24 hours.
2:25:17And the fuel use is going to change. The
2:25:19brain relies on glucose and also ketone
2:25:22bodies. Muscles and other tissues rely
2:25:24on fatty acid oxidation. So, the
2:25:26pathways that are upregulated would be
2:25:28gluconneogenesis because that's how
2:25:30we're going to make new glucose if we
2:25:32don't have any lipolyis and also beta
2:25:35oxidation. Maybe also ketogenesis and
2:25:37protein catabolism because that will
2:25:39provide us with our gluconneogenic
2:25:41substrates. And the down reggulated
2:25:43pathways because these guys are
2:25:44upregulated would be your glycolysis,
2:25:47glycogen synthesis. It's already
2:25:48exhausted, right? Fatty acid synthesis
2:25:51and protein synthesis. And how they're
2:25:53going to get you is they're going to ask
2:25:54about these intermediates and
2:25:55substrates. They're going to say, "Okay,
2:25:56would this be elevated or not?" Now, you
2:25:58guys are probably looking at this one
2:26:00from your MCAD days and saying, "I've
2:26:01seen that before." Well, that is going
2:26:03to be downregulated. that normally
2:26:05activates glycolysis through PFK1 and in
2:26:07starvation we suppress that right so
2:26:09we're going to bring that down what
2:26:11about pyuvate kynise well that is the
2:26:13last step of glycolysis and so that's
2:26:15also going to be down it's suppressed so
2:26:16that the substrates can go into the
2:26:18gluconogenesis instead and then there
2:26:20are some other steps that are involved
2:26:22in gluconneogenesis right and that's
2:26:24like glucos 6 phosphatase that's going
2:26:26to be upregulated that's the final step
2:26:28in gluconioenesis right that's where you
2:26:30release the free glucose into the blood
2:26:32and pepsk K is the key step in
2:26:35gluconioenesis as well. So Pepsi K is
2:26:37going to be elevated whereas the other
2:26:39guys are going to be decreased. So
2:26:41prolonged fasting the liver shifts
2:26:43toward the glucose production and also
2:26:45export not utilization. And so the key
2:26:47aspect of this topic is knowing that
2:26:49pepsk and glucose 6 phosphatase are
2:26:52upregulated and glycolysis enzymes like
2:26:54pyuvate kynise PFK1 through fructose 26
2:26:59bifphosphate are going to be
2:27:00downregulated. So downregulated,
2:27:02upregulated, glycolysis, gluconioenesis.
2:27:05And so our answer is increased
2:27:07phosphenol pyuvate, pepk and glucose 6
2:27:10phosphatase. There we go. The answer is
2:27:12D. Pyuvate kynise and fructose 26 bif
2:27:15phosphate promotes gly glycolysis.
2:27:17Malanil coa is seen in the fed state
2:27:19downregulated in fasting. Suppressed
2:27:22G6PAs
2:27:24well that's needed to release the
2:27:25glucose in the bloodstream so you can't
2:27:26suppress it. high citrate. Citrate
2:27:29builds up only in high energy fed
2:27:31states. So yeah, your liver actually
2:27:32kind of turns into like a glucose
2:27:34factory after 24 hours of not eating.
2:27:37Your liver is like, "Let me fix that."
2:27:39So your body is starved of food and it
2:27:41just adapts. Your hormones just change
2:27:43and it just flips your metabolism
2:27:44around. No big deal. All right. In our
2:27:46next question, we have a 35-year-old
2:27:48woman presenting with fatigue, blurry
2:27:50vision, and persistent dry cough. She
2:27:51has recent joint stiffness, and painful
2:27:53red nodules in the shins. I'm also
2:27:55giving you this demographic because I
2:27:57think it's super important to also know
2:27:59for test day. Her temperature is 99.5.
2:28:02Blood pressure is 10 120 over 76.
2:28:06Opthalmologic exam shows interior
2:28:08viitis. Bilateral hiler lympadinopathy
2:28:11is present. We also have elevated ACE
2:28:13levels. Trans bronchial biopsy revealed
2:28:16well-formed non-gaciating granulomaas.
2:28:18This should all be making us think of
2:28:19sarquidosis. Bilateral hympadnopathy,
2:28:22uvitis, aiththemmaosum. Are you kidding
2:28:25me? This is sarcoidosis 100% of the
2:28:27time. Now, what's the predisposing
2:28:28factor? Well, anytime you see a patient
2:28:31with bilateral hiler adinopathy
2:28:33lympadnopathy and maybe they'll have
2:28:35like a paratrachial enlargement and on
2:28:37biopsy, they're always going to show you
2:28:39nonaciating granulomaas. What they're
2:28:42trying to tell you, they're just
2:28:43screaming it out to you is sarcidosis.
2:28:45Okay, there's some key diagnostic
2:28:47features for sarcidosis. non-inciating
2:28:49granulomaas, bilateral hilo
2:28:51lympadnopathy, and African-American
2:28:53population and also women. Those are the
2:28:56most important things to know. You
2:28:57should also know outside of that that
2:28:59it's like 20 to 40 years old. I've never
2:29:01seen a question whether or not
2:29:02African-American women 20 to 40
2:29:05bilateral hympadinopathy and nonian
2:29:07granulmas just just literally click
2:29:09sarcoidosis. It is right every single
2:29:11time. Anytime you see those patient
2:29:13characteristics, it's going to be
2:29:14saridosis. Now the manifestations are
2:29:16uvitisthemodosa hypercalcemia and the
2:29:19hypercalcemia is interestingly from
2:29:21increased alpha hydroxilase activity in
2:29:23the macrofasages and I think this is an
2:29:25important mechanism to know the
2:29:27macrofasages increase alpha hydroxilase
2:29:30and you could also see restrictive lung
2:29:32disease if it's chronic as well and so
2:29:34what I'm doing here in this question is
2:29:35I'm just teasing out these risk factors
2:29:37which are super high yield in the exam
2:29:38these days sarcoidosis non-case heating
2:29:40hypercalcemia female sex it's all strong
2:29:43bird exposure hypersensitivity numinitis
2:29:45Smoking is not a risk factor for it. In
2:29:47fact, it may actually be protective.
2:29:49Northern European ancestry is not it.
2:29:51It's African-American ancestry and
2:29:53travel to Arizona's coxidio micosis
2:29:56paciating granulomis. Now, sarquidosis
2:29:58is often called, interestingly enough,
2:30:00the great mimic because it can resemble
2:30:02like everything from like lung cancer to
2:30:04tuberculosis, honestly. Okay. Next, we
2:30:06have a 13-year-old boy recovering after
2:30:08surgery for a displaced supraondular
2:30:11humorous fracture. after his arm was
2:30:13immobilized in a long arm cast for 4
2:30:15weeks. After followup, he reports
2:30:16difficulty performing push-ups, which he
2:30:18used to do them easily. Physical exam
2:30:20reveals visible muscle thinning of the
2:30:22triceps and deltoid. Which of the
2:30:23following is most likely observed? So,
2:30:25we got a young kid, forearm fracture,
2:30:26immobilized, and a cast. And then 3
2:30:29weeks later, the muscles are no longer
2:30:31going to be used. What happens to these
2:30:32immobilized muscles? For this one, we
2:30:34have to talk about use and disuse. So
2:30:37active loaded muscles have increased
2:30:39metabolic rate, increased mitochondrial
2:30:42activity and also increased angioenesis
2:30:44and that's through veg f. You also have
2:30:46increased capillary density and you have
2:30:48increased local vasoddilators like
2:30:50adenazine, lactate, CO2, hydrononeium
2:30:53ions, right? So you're going to have
2:30:54like increased blood flow. If you're
2:30:56inactive, then you kind of have the
2:30:58opposite. You have decreased trophic
2:31:00stimulation. There's another word for
2:31:01that would be like you have atrophy,
2:31:03increased atrophy. You also have
2:31:05decreased metabolic demand. There's
2:31:06atrophy of the sarcimeirs and most
2:31:08importantly we decrease your veg.
2:31:10There's decreased angioenesis signals.
2:31:12There's decreased capillary density. So
2:31:14he has his arm immobilized and the
2:31:16answer is going to be microvascular
2:31:18density. So yeah, you just hold your arm
2:31:20like this. Don't even move it. Put in a
2:31:22cast 3 weeks your muscles are going to
2:31:23shrink and also the blood supply does
2:31:25too. It starves your muscles. Now these
2:31:27other answers are interesting. Increased
2:31:29mitochondrial biogenesis would be like
2:31:30if you're training for a marathon doing
2:31:32endurance training, you could see that.
2:31:33Increased tissue oxygen extraction would
2:31:35be eskeeia. Hi, one alpha expression
2:31:38hypoxia. That's when it's not reaching
2:31:40the tissues. And increased intracellular
2:31:41lactate would be anorobic glycolysis.
2:31:44That's wrong because inactive muscles
2:31:45don't perform anorobics. Next, we have a
2:31:4724-year-old man with recurrent
2:31:49generalized tonicclonic seizures that
2:31:51began 3 weeks ago. Immigrated to the
2:31:54United States from Guatemala. Tonight is
2:31:56any history of trauma, substance use or
2:31:58past medical issues. Neurologic exam is
2:31:59unremarkable between episodes.
2:32:01Non-contrast CT of the brain reveals
2:32:03multiple cystic and calcified lesions
2:32:05scattered throughout the cerebral
2:32:06cortex. Some with central dodlike
2:32:08structures. Blood tests are normal
2:32:10except for mildenophilia.
2:32:12Which of the following is most likely
2:32:14causal organism? Now you could also see
2:32:15this in old, young, male, female. And so
2:32:18here I have a young female. This person
2:32:21is usually going to be an immigrant of
2:32:23Guatemala, Mexico, something like that.
2:32:25So, multiple cystic calcified lesions,
2:32:28central dotlike structures, and their
2:32:30new onset seizures. Usually, the most
2:32:32important things to know about this
2:32:34particular issue is that they're going
2:32:35to be previously healthy. They're from
2:32:37Mexico or Guatemala. They're an
2:32:39immigrant essentially. And then out of
2:32:41the blue, they have some short amount of
2:32:42time where they start to get seizures.
2:32:44And then the CT of the brain shows
2:32:45multiple calcified nodules and also some
2:32:47cysts. So cyst and nodule everything
2:32:50else is pretty normal. So it's really
2:32:52that multiple cystic and calcified brain
2:32:54lesions that's in somebody from Latin
2:32:56America that tells you it's neuroscystic
2:32:58crosis. So watch out for that dot sign
2:33:01tinusia. It's the larae that are
2:33:03responsible and the seizures are common
2:33:05due to the inflammatory response around
2:33:07these cysts. So the cysts get all ugly,
2:33:10inflammation happens, you have one week
2:33:12of just seizing in a previously healthy
2:33:14person from an endemic region and also
2:33:16you have some nodules. That's pretty
2:33:18much all there is to know about
2:33:19tenosolium. Now they'll try to confuse
2:33:21you and they'll try to make you think of
2:33:23other conditions like cryptocous
2:33:24neopformance but that one is not going
2:33:26to lead to the symptoms we see in this
2:33:28patient necessarily rather it leads you
2:33:30a little bit more toward menitis and
2:33:31that's usually in immunompromised
2:33:33individuals not previously healthy
2:33:34people and definitely you aren't going
2:33:36to see multiple cystic lesions herpes
2:33:38simplex virus would cause encphilitis
2:33:40and that's usually in the temporal lobe
2:33:42necrosis and HIV predisposes you to
2:33:45operistic so CNS infections listia
2:33:48causes menitis and abscess test
2:33:50streptoccus pneumonia that's meningitis
2:33:53toxo would have multiple ring enhancing
2:33:55lesions inimunompromised you have to
2:33:57know that this is a previously healthy
2:33:58child all right or a previously healthy
2:34:0024y old man started 3 weeks ago all
2:34:02right here we have a 28-year-old woman
2:34:05it could also be a 28 or something year
2:34:07old man just showing you a different
2:34:08demographic could be nearly anybody
2:34:11nasal congestion watery rhinora sneezing
2:34:13for the past couple days the symptoms
2:34:14occur every April and October okay so
2:34:17some allergies you have boggy
2:34:19pale nasal mucosa with clear discharge.
2:34:22She wants immediate relief for the
2:34:23upcoming job interview. What drug are
2:34:25you going to give her? Probably
2:34:26fenylphrine. Short-term relief. Kind of
2:34:28contraindicated in the elderly because
2:34:30of beer's criteria. Short-term relief
2:34:31would be an alpha 1 adinuric agonist. So
2:34:34there's our answer B. And the
2:34:35pathophysiology is interesting here. In
2:34:37allergic rhinitis, you have histamine
2:34:39release and parasympathetic activation.
2:34:41And that causes vasoddilation and
2:34:43increased secretions of the nasal mucos.
2:34:45And so for treatment longterm you give
2:34:46them intraasal cortical steroids like
2:34:49oral intraasal antihistamines. So you
2:34:52stop those histamines from spreading
2:34:54out. And short-term immediate relief you
2:34:56give them an alpha 1 adinuric agonist.
2:34:59That could be topical oral
2:35:00decongestions. So alpha 1 adinuric
2:35:03agonist would be like phenylphrine,
2:35:05zolene, pseudoephidine. Those are alpha
2:35:071 activators vasoc constricting. And so
2:35:09they constrict on that nasal mucosa and
2:35:12you get decreased edema, decreased
2:35:14secretions and rapid relief. You also
2:35:16have alphaurgic antagonist and those
2:35:18guys would cause you know vasoddilation
2:35:20and that would make things worse.
2:35:21Betaurgic agonist like albuterol use
2:35:24this for broncoilation for asthma.
2:35:26Betaurgic antagonist would be like
2:35:27propanol. Nicotinic
2:35:30agonist would be like nicotine that
2:35:32would not even help. So our answer is
2:35:33indeed going to be B. While the
2:35:35miscarrenic antagonist would have a
2:35:36drying effect wouldn't have that relief.
2:35:38It's more used for COPD. H1 histamine
2:35:40receptor antagonism used for itching and
2:35:43sneezing slower onset not ideal for
2:35:44acute relief. Lucatrine Montalucast used
2:35:47for asthma not fast acting and a cortica
2:35:49steroid nasal spray would be long-term
2:35:51control slower. So a lot of people have
2:35:53allergic grinitis. The reason why is cuz
2:35:55that springtime pollen will hit and so
2:35:57you know you got to get some some sort
2:35:58of relief. So you got to constrict that
2:36:00nasal mucosal vessel. All right. All
2:36:01right. So, here we have a 31-year-old
2:36:03woman with a history of poorly
2:36:04controlled type 1 diabetes. Evaluation
2:36:06of chronic bloating and early saty. It's
2:36:09not specific to female. So, I've given
2:36:11you a male over here as well. She
2:36:12started on a new medication that binds
2:36:14to receptor in the smooth muscle of the
2:36:16upper GI tract and improves gastric
2:36:18motility. What describes the mechanism?
2:36:20All right. So, we're increasing the
2:36:21contractility of the stomach. Well,
2:36:22there's this thing called the migrating
2:36:24motor complex, the MMC, and that causes
2:36:27the the waves of the electrical and
2:36:29contractile activity that occur during
2:36:31fasting about every 90 to 120 minutes.
2:36:33And so the function is going to be it
2:36:35clears the residual food and bacteria
2:36:37between the meals. It's like a
2:36:38housekeeping. And motel is the hormone
2:36:41that initiates that motor complex. It
2:36:44activates the G-proin coupled receptors.
2:36:46It increases the gastric contractions,
2:36:48you know, the antrum, the fundus. It
2:36:49stimulates the paristtoalsis of the
2:36:51small bowel. And so clinically like
2:36:52arythrammyosin which is a modalin
2:36:54receptor agonist is used to stimulate
2:36:56the gastric motility. So our answer is B
2:36:58the activation of the modilin receptors.
2:37:00Gastropriesis diabetes impaired MMC
2:37:03modilin agonist like ariththramthyosin
2:37:05stimulated D2 antagonist metropomide
2:37:08acts this way but causes extra perimeal
2:37:10symptoms like tardive disynesia. It
2:37:11improves motility indirectly not through
2:37:14the MMC. 5HT3 blockade, odancetron does
2:37:18not stimulate motility but it does block
2:37:20the ematic pathway. Hydrronium potassium
2:37:23ATPAS inhibitor proton pump inhibitor
2:37:25that reduces the acid on the motility
2:37:27CB-1 promotes the hunger. So basically
2:37:30for this question we need to know that
2:37:31your stomach has its own cleaning cycle
2:37:33every 90 minutes or so. When you're not
2:37:35eating there's this migrating motor
2:37:37complex. It's powered by modolin and
2:37:39ariththroyioin
2:37:41can actually mimic that. So serotonin is
2:37:43more of a modulator of you like that 5HT
2:37:45your motility and secretion but the
2:37:47effects are going to be super broad and
2:37:48stuff. The direct triggering of the MMC
2:37:51like this question is asking is going to
2:37:53be motil. Norepinephrine will be
2:37:55sympathetic that would decrease
2:37:56motility. Acetylcholine would be a
2:37:58veagal parasympathetic so would
2:37:59stimulate secretion and motility but
2:38:01it's not going to be the most specific
2:38:02example. Bind to the smooth muscle of
2:38:04the upper GI tract and improve the
2:38:06motility. Motelin 28-year-old healthy
2:38:08man is hiking a mountain lodge situated
2:38:10at elevation where the atmospheric
2:38:11pressure is at 600 avular carbon dioxide
2:38:14partial pressure is 40 respiratory
2:38:16exchange is8 what is his estimated
2:38:18aviolar partial pressure all right so
2:38:19breaking this down atmospheric pressure
2:38:21is 600 that's where like our altitude is
2:38:24fraction of oxygen ambient air is 21 and
2:38:26this is going to stay constant at
2:38:28altitude the water vapor is constant at
2:38:3047 so you would subtract that from
2:38:32atmospheric pressure and we use the
2:38:34avular gas exchange equation equation,
2:38:36which is going to be this guy right
2:38:38here. So, we just plug it in to our
2:38:40equation and we get 66. And we have to
2:38:42subtract the water vapor. That's like
2:38:44the only hard part of this is
2:38:45subtracting the water vapor and you get
2:38:4666. Now, I hate this cuz it's a lot of
2:38:48just memorization, right? The big thing
2:38:50to know is that the fraction of inspired
2:38:52oxygen room air would be 21. You just
2:38:54have to know that of the water vapor
2:38:56pressure at the body temperature is 47.
2:38:58That's what you need to know. If you
2:39:00know that, you're good to go. Okay,
2:39:01these two variables are worth
2:39:03memorizing. And with that, we'll see you
2:39:05soon for the rest of the video. Hello
2:39:07everybody. MVME 29, question 101. All
2:39:10right, this is an ethics question. We
2:39:11need to make sure that we always
2:39:12validate the emotions. Okay, so here's
2:39:14your practice question. 23-year-old
2:39:16college student is brought by his sister
2:39:18due to changes of behavior the past 8
2:39:19months. She reports he has isolated
2:39:21himself, stopped attending to classes,
2:39:22and frequently mumbles himself in his
2:39:23room. He has not bathed. He's unckempt.
2:39:26Makes eye contact. His sister begins to
2:39:28cry, saying, "I don't even recognize
2:39:29him." Which of the following is the most
2:39:31appropriate initial response by the
2:39:32physician? The answer is that must be
2:39:33incredibly difficult. Can you tell me
2:39:35more? Always validate first. Right? When
2:39:37everybody anybody describes emotion when
2:39:39discussing a medical concern, the
2:39:40physician should always be like, I, you
2:39:42know, I agree that it's ex emotion that
2:39:44you're feeling. Always validate. After
2:39:46you validate, then you can start to ask
2:39:47the open-ended questions. Okay, they're
2:39:49the trap answers why they're wrong. So,
2:39:51here are some notes. Validate emotions.
2:39:52Ask open-ended questions. Don't dump to
2:39:54diagnosis. Don't offer judgmental advice
2:39:56like, "Oh, you need a shower." Also, be
2:39:58on the lookout for positive symptoms of
2:39:59hallucination. Negative symptoms would
2:40:01be the poor hygiene, social withdrawal.
2:40:03Schizophrenia would have both clusters
2:40:05over 6 months. All right. Next, we have
2:40:06a 73y old man, but it could also be a
2:40:08woman. Here I have that in my
2:40:10demographic photo. Coming for routine
2:40:11evaluation reporting no significant
2:40:13complaints. Lab shows an M spike of 2.1
2:40:17serum protein electropheresis bone.
2:40:19Mirror biopsy shows 5% plasma cells. His
2:40:21hemoglobin is 13.2 calcium 9. Crain
2:40:24is.9. He denies bone pain and fatigue.
2:40:28Weight loss has noic lesions. Which of
2:40:30the following is the diagnosis? Correct
2:40:31answer is D monchromal gmopathy of
2:40:34undetermined significance. So there are
2:40:36some things that we have to kind of know
2:40:37here. The M spike would be less than
2:40:39three for this condition and also less
2:40:41than 10% of your plasma cells in the
2:40:43marrow. And most important like on step
2:40:45one is to know these crab symptoms. You
2:40:47probably heard of crab. Really good
2:40:49acronym. That's hypercalcemia, renal
2:40:51failure, anemia, bone lesions. He denied
2:40:54those things. It's super important that
2:40:55they mentioned that. And this condition
2:40:56is benign, but it can progress later on
2:40:58to a melanoma. It's about like 1% per
2:41:00year. There are some other answers like
2:41:02smoldering and I'd say okay what's
2:41:04smoldering myoma? That's an M spike
2:41:06that's greater than three grams per
2:41:08deciliter or greater than 10% plasma
2:41:10cells. And there you would have your
2:41:11crab findings, right? So it's all about
2:41:13the hypercalcemia, renal failure, anemia
2:41:15and the bone lesion stuff. There's also
2:41:16Walden micro Waldenstrom macrolin
2:41:19globular anemia. Waldenstrom macrolabbul
2:41:22anemia and there you have an IGM spike,
2:41:25not an IGG spike. There you have like
2:41:27headaches, blurred vision, bleeding,
2:41:29neuropathy, that stuff. Chronic liver
2:41:30disease and chronic inflammation that
2:41:32causes polychromal hyperamoglobinia, not
2:41:34a sharp monocomal spike. So what we're
2:41:37going to be doing on a question like
2:41:38this is we have to match it to the
2:41:39vignette. Right here we have an M spike
2:41:40of less than 10% in the marrow and no
2:41:42crab features. Multiple myoma has those
2:41:44litic bone lesions and you need greater
2:41:46than 10% of the plasma. Smoldering
2:41:48multiple myoma would be asymptomatic
2:41:50with an M spike of greater than three.
2:41:52Here we had an M spike of less than
2:41:54three. Waldenstrm has a monocchromal
2:41:56IGM. You know that because the M there
2:41:58Waldenstrum IgM hyper viscosity and CLL
2:42:01would have the smudge cells. And the way
2:42:03I like to remember this one is I can see
2:42:05clearly now the smudge has gone. Right?
2:42:08I can see CL I always remember cleanly
2:42:11now the smudge is gone. Lymphocytosis
2:42:12with smudge cells. All right. So we got
2:42:14a 73y old totally fine but now we have
2:42:16an M spike 5% plasma cells. There's no
2:42:19crab MGS early stage clonal plasma cell
2:42:22disorder for management. It's just
2:42:24monitoring you know labs and symptoms
2:42:26and no treatment is necessarily needed
2:42:27with this monocchromal gumopathy of
2:42:29uncertain significance. So simply just
2:42:31to make it really clear anytime you see
2:42:34multiple myoma you should look out for
2:42:35crab symptoms and also you need greater
2:42:38than three gram per deciliter spike or
2:42:40greater than 10% of the plasma cells and
2:42:43also you need those crab symptoms.
2:42:45Smoldering is greater than three spike
2:42:47but no symptoms. Walden strumm is an IGM
2:42:50spike, not IGG. Chronic liver disease
2:42:53and inflammation would have a polyclonal
2:42:55increase, not just one single sharp
2:42:57spike. So we got this disease kind of
2:42:59harmless for now, but that's what's
2:43:00going on in this patient. Okay, next we
2:43:02are on 103 here. In a study of vascular
2:43:04permeability, researchers apply a mild
2:43:07heat stimulus in the dorsal skin of rats
2:43:08for 20 seconds and observe bifphasic
2:43:12extravisation of the injected die. First
2:43:15peak occurs in 20 minutes. Second
2:43:16broader peak after 4 to 6 hours.
2:43:18Follow-up trial group of rats
2:43:20pre-treated with non-stating H1 blocker.
2:43:23Which of the following best describes
2:43:24the effect of the antihistamine? Okay,
2:43:26so basically after you get like a burn,
2:43:28you have two waves of leakiness, which
2:43:31is another word for extravisation,
2:43:34leakiness. There's an early one and
2:43:36there's a late one. This early one is
2:43:37just minutes after and it's driven by
2:43:39mast cell histamine and that is H1 that
2:43:42causes arterial vasoddilation and
2:43:44venular endothelial gap formation and so
2:43:47this causes the plasma to go ahead and
2:43:49leak out. Then there's this later peak
2:43:51that's hours later and that's driven by
2:43:52the cytoine mediators from the damaged
2:43:54tissue and it's recruited lucasytes so
2:43:56like TNF alpha1
2:44:00prostaglandins bradkinine all that
2:44:02stuff. So an antihistamine will block
2:44:04the early histamine mediator response
2:44:06and it'll blunt that first one.
2:44:08Antihistamine and not necessarily this
2:44:10second one. Cytoine mediated
2:44:12inflammation persists independent of
2:44:13histamine preventing both peaks. Delays
2:44:16onset of the second peak. Cytoines are
2:44:17released. Attenuates only the late peak.
2:44:19Antihistamine does not affect
2:44:20prostaglandins and cytoines. Has no
2:44:22effect. Histamine clearly mediates the
2:44:25initial vascular response. So here's a
2:44:27little explanation if you want to pause.
2:44:28There's that first wave, second wave,
2:44:30first wave. Mass cells dump histamine
2:44:32get dilation and capillary leakage early
2:44:34fluid leak and then cytoines TF alpha
2:44:36show up there's a second wave right so
2:44:38our first histamine mass cells and then
2:44:41you have the swelling that's caused by
2:44:43the cytoines histamine cytoines all
2:44:46right so in this next question we need
2:44:47to know about the external iliac artery
2:44:49there's the soaz major there's our
2:44:51femoral artery common iliac external
2:44:54inferior epigastric and the deep
2:44:56circumlex iliac artery there's this
2:44:58inguina ligament here now there are a
2:45:00couple of things There's the uterero
2:45:02pelvic junction. That's where the renal
2:45:03pelvis meets the urer. There's the
2:45:05pelvic brim. That's where the urer
2:45:07crosses the external iliac vessels. So,
2:45:09you know, urinal pelvis, urtors,
2:45:12bladder, urer, external iliac. So, as
2:45:15major, just trying to show this from
2:45:16different angles. Uelic junction right
2:45:18here. Uliac artery right here. There's a
2:45:20good little drawing. So, this uterelic
2:45:22junction, that's where the renal pelvis
2:45:24meets the urer. You can see it right
2:45:25here. Uicular junction, that's where the
2:45:27urer enters the bladder. And the pelvic
2:45:29brim is where the urer crosses the
2:45:32external iliac vessels. Right? So those
2:45:34are kind of the big three sites, the
2:45:36urer narrowing sites. And that's where
2:45:37the stones often will get stuck. And so
2:45:39in this question, they're going to be
2:45:40like, "Hey, we got like a stone. It's
2:45:42just chilling. It's above the sacraliac
2:45:44joint." Okay. Well, that's going to be
2:45:45the pelvic brim. And at the pelvic brim,
2:45:48the urer crosses the external iliac
2:45:50vessel. And that is what narrows the
2:45:52passage. So here you can kind of see it
2:45:54in this photo. I zoom in right there.
2:45:56See how it's kind of crossing right
2:45:58there, right at the pelvic brim, your
2:45:59pelvic junction. Yeah, this is a pretty
2:46:01good photo. You can kind of see these
2:46:02three distinct spots where it's going to
2:46:03be narrowed at and those are the
2:46:05external iliac. So in this question, we
2:46:07have a 28-year-old G1, 20 week, sudden
2:46:11right-sided cramping, flank pain,
2:46:13anterior thigh with nausea, no fever,
2:46:15passes anterior to which structure iliac
2:46:18artery. Here's explanation. And we kind
2:46:19of looked over this together, but what
2:46:20there is to know is that the uriteral
2:46:22stones are going to get stuck at the
2:46:24three most distinct and kind of
2:46:26predictable choke points. Uropo pelvic
2:46:28junction, the pelvic brim, utericular
2:46:30junction. So it's where the urer crosses
2:46:32the external iliac vessels and then
2:46:34where the urer actually enters into the
2:46:35bladder. Those are the three areas you
2:46:37should know. And so it's just above that
2:46:39sacroiliac joint. That's the pelvic
2:46:41brim. And at that pelvic brim, you're
2:46:43going to cross the external iliac
2:46:45vessel. Tada. All right. For this one,
2:46:46we're going back to the drawing board.
2:46:47We were on question 104. So let's talk
2:46:50about an ROC curve. So typically how
2:46:52this plays out is the y-axis. This is
2:46:54like the sensitivity. See how it says
2:46:56true positives? That's the same thing as
2:46:57sensitivity. X-axis is one minus the
2:47:00specificity, which is to say the false
2:47:01positive rate. And so you know, if it's
2:47:04higher up, then that means it's more
2:47:05sensitive. There are fewer false
2:47:07positives. And so if you're looking for
2:47:08like a fatal disease, the most important
2:47:10thing is you don't want to miss anybody
2:47:11who has it, right? You want that cut
2:47:13point to be at where the highest
2:47:15sensitivity is. If you pick a very
2:47:17sensitive cut point, then you're going
2:47:18to get more false positives that has
2:47:20lower specificity. And that's fine if
2:47:21you're screening because positives can
2:47:23then be confirmed with more specific
2:47:24follow-up testing. But false negatives,
2:47:26like missed cases being deadly, that's
2:47:28super bad. So on an ROC curve like over
2:47:31here would be the highest sensitivity.
2:47:33So if it's a serious disease, but it's
2:47:35treatable, definitely pick the most
2:47:36sensitive test. And you can remember
2:47:38this by if it's sensitive, remember
2:47:40snout sensitivity being negative rules
2:47:42out the disease. So here it says a new
2:47:45bloodbased assay is being developed to
2:47:48detect an aggressive cancer that is
2:47:49asymptomatic early but rapidly fatal if
2:47:52not treated. ROC curve below
2:47:53demonstrates five potential cut points
2:47:54based on assay values. The goal is to
2:47:57use this assay for populationwide
2:47:59screening. Which cut point should be
2:48:01selected to maximize early disease
2:48:03detection? And then they're going to
2:48:04give you an ROC curve that kind of looks
2:48:05like this. And it's going to be the one
2:48:07that's highest up, right? Because that's
2:48:08going to be sensitivity. Sensitivity. If
2:48:11you're sensitive, it's truly a positive
2:48:13trait, right? In a person. You want
2:48:14somebody who's sensitive in a person,
2:48:15right? Well, it's truly a positive
2:48:17trait. So, it's true positive. You want
2:48:19that to be as high as possible because
2:48:21snout. If it's sensitivity, it has a
2:48:23high sensitivity, but it's negative,
2:48:24that rules out the disease, snout. So,
2:48:27the answer is E, which is right here,
2:48:29super high up. The other ones are going
2:48:31to be lower. Yep. ROC stands for
2:48:33receiver operating characteristic. You
2:48:35don't want somebody thinking that
2:48:36they're fine, but they're not. If the
2:48:37disease is fatal, if it's not fatal,
2:48:39sure it's fine. So that's the RSC curve.
2:48:41All right. Here we have a 17-year-old
2:48:42male evaluated for academic difficulties
2:48:44and behavioral issues. His teachers
2:48:46report poor social interaction and
2:48:49repetitive speech. On exam, he has long
2:48:51narrow face, enlarged ears, and
2:48:53macroorganism.
2:48:54Family history reveals maternal
2:48:56grandfather with late onset tremor and
2:48:58atexium. We have a lot of these 250 CG
2:49:01repeats. That was overkill of them to
2:49:03say. Which of the following describes
2:49:05the consequence of this mutation? It is
2:49:06the transcriptional silencing through
2:49:08DNA and methylation. All right. So this
2:49:10we move on is fragile X. The GG stands
2:49:13for giant gonads. That's the way to
2:49:16remember it. But it's a CGG expansion of
2:49:18the fivep prime UTR of the R1 gene FMR1.
2:49:22So that region becomes hyperthylated.
2:49:24The methylation blocks the transcription
2:49:26factor RNA pulymerase access and then
2:49:28the transcription gets silenced. So you
2:49:30decrease FMR1 mRNA. So you can remember
2:49:33this as like the giant gonads the C gg
2:49:36or you can say it causes it to go quiet
2:49:39causes gene to go quiet fMR1 giant
2:49:43gonads fragile axe the phenotype is
2:49:46intellectual disability long face large
2:49:47ears so maybe another way you can
2:49:49remember this too is the C kind of looks
2:49:51like large ears on a person see like
2:49:53that and then giant gonads all right so
2:49:55you kind of can imagine a person and
2:49:57that's just the way that has stuck with
2:49:59me for fragile X it's not increased
2:50:01translation
2:50:02It's not actually translated. It's
2:50:03silenced. Increased intron splicing
2:50:05affects the mRNA, but the transcript's
2:50:07not made there. Incorporation, it's not
2:50:09applicable. It's in a non-coding region,
2:50:10never entering. Impaired nuclear export,
2:50:13there's no mRNA to export due to the
2:50:15transcriptional silencing. It's the most
2:50:17common inherited cause of intellectual
2:50:19disability. So, the splicing defects,
2:50:21that's the intron exxon stuff. MRNA
2:50:23degradation, that's poly A issues.
2:50:26Incorporation, the repeats are not
2:50:28transcribed at the m mRNA. they're going
2:50:30to silence upstream. So like all these
2:50:32like repeats that you have, the repeats
2:50:35are not transcribed into mRNA, they just
2:50:37silence. So methylation would reduce the
2:50:40binding of RNA polymerase as well. Also,
2:50:42I realized that my photo was kind of
2:50:44blocking everything there, but hopefully
2:50:45you can see my notes here on fragile X.
2:50:47And now I'm going to move on to 107. All
2:50:49right, here a 71-year-old woman is
2:50:51presenting with difficulty swallowing
2:50:52that began gradually over the past 3
2:50:54months. She reports occasional coughing
2:50:55while eating and has unintentionally
2:50:57lost 4 lbs. She denies an eodenaphasia
2:51:00or regurgitation. Her recent medical
2:51:02history shows hypertension and remote
2:51:03history of roheatic fever. Chest X-ray
2:51:05shows cardiomegaly with a prominent left
2:51:07heart border. Berium esophag reveals
2:51:10posterior displacement of the mid
2:51:11esophagus. Which of the following is
2:51:13most likely responsible for these
2:51:14symptoms? Okay, you have to know how the
2:51:16heart sits for this one. So, I'm going
2:51:18to go ahead and give you the answer.
2:51:19It's the left atrium that's the most
2:51:20posterior chamber of the heart. It lies
2:51:22just in front of the esophagus of the
2:51:24medastinum. And if the left atrium
2:51:26enlarges for instance if we were to have
2:51:28dilated cardiammyopathy right if
2:51:31something like that were to happen or
2:51:32you were to have like a mitro valve
2:51:34disease or something like that then it
2:51:35can press up and displace the esophagus
2:51:37and that will show up on the barerium
2:51:39swallow as a posterior indentation and
2:51:41that will cause dysphasia especially to
2:51:43solids. The left ventricle that's more
2:51:46inferior and also lateral. The right
2:51:48atrium that forms the right heart
2:51:49border. The right ventricle is the most
2:51:51anterior chamber and the superior vennea
2:51:53is not adjacent to the esophagus. So
2:51:55left atrium lies directly anterior to
2:51:57the esophagus and posterior to the
2:51:58medastinum. So yep, an enlarged heart
2:52:01can make it hard to swallow. That's the
2:52:03main story here. You have to know that
2:52:05it's left atrium which sits like
2:52:07directly in front of your esophagus. And
2:52:08always try to envision like a patient in
2:52:10front of you staring at you like you're
2:52:12diagnosing them. That left side, the
2:52:13heart's kind of tilted like this. Looks
2:52:15like a boot inside of their body. Also
2:52:17on that last one, if you want to
2:52:18remember, LA stands for lies against.
2:52:21Maybe that's an easy way to remember it.
2:52:22It lies against the esophagus. LA, left
2:52:25atrium. Okay. Next, we have a
2:52:2626-year-old man presenting the clinic
2:52:28with recurrent episodes of colored urine
2:52:30that last 1 to two days after episodes
2:52:32of fngitis. He denies dyseria or flank
2:52:34pain. Past medical history is
2:52:36unremarkable. Blood pressure is 140 over
2:52:3888. Physical exam is normal. Urine
2:52:40analysis shows three plus blood, two
2:52:42plus protein. and dysmorphic red blood
2:52:44cells. Renal biopsy shows granular
2:52:46immune deposits and serum C3 and C4 are
2:52:49normal. Okay, this is IgA IgA
2:52:51nephropathy. So we got a dude, he's got
2:52:53some episodes of some brown urine
2:52:55hematia that appears during a
2:52:57respiratory infection, URI GI problem
2:52:59and this is going to be IgA nephropathy,
2:53:02burger disease. This happens because of
2:53:04mucosal infections like respiratory GI
2:53:06and that will trigger an IgA
2:53:08overproduction is the mechanism and that
2:53:11deposits in the glomemeular messium. And
2:53:13so on biopsy you have granular IgA
2:53:15deposits in the meantium and you could
2:53:17think of other options like IGD nobody
2:53:19really cares about that one that's only
2:53:21on the autoimmune B cells or IGM that's
2:53:24really early in the process of the
2:53:26immune response. It's not going to be
2:53:28the driver of burger disease at all.
2:53:29That's IgA and Ig is allergic reactions,
2:53:32not the kidney. So IGA nephropathy, the
2:53:34infections activate the IgA. You get
2:53:37hematia with colds or GI problems.
2:53:40Here's an explanation. Linear IGG would
2:53:42be good pasture syndrome. Full house
2:53:44pattern lupus low compliment all that
2:53:46stuff. IGM focal segmental
2:53:49glomemecerosis is a pattern in HIV.
2:53:52Subepithelial humps IGG and C3 is
2:53:54postpocal glomephritis. So it causes
2:53:57blood in the urine just like a day or
2:53:59two after you have an upper respiratory
2:54:01infection. All right, here's some more
2:54:02information about it. Granular IGA in
2:54:04the messenium nephropathy with the young
2:54:05adult hematia after upper respiratory
2:54:07infection or GI red blood cell cast and
2:54:09normal C3. It's not lupus or good
2:54:11pasture. Linear IGG is a type two
2:54:13hypersensitive reaction reaction where
2:54:15the answer is good pastures. You have a
2:54:17glomemeular basement membrane and inside
2:54:20of that the alpha 3 chain of type 4
2:54:22collagen is damaged with those IGGs. So
2:54:25you have linear IGG staining. IgA would
2:54:27be granular, not linear. Also involves
2:54:29the lung. Smopsis would be seen. All
2:54:31right. In this next question, look, it's
2:54:32you, a researcher. Oops, there we go.
2:54:35They're comparing the energy yield of
2:54:37different organic compounds, each
2:54:38containing six carbon atoms. Researcher
2:54:40observes that one compound generates
2:54:42significantly more, which the following
2:54:43characteristic most likely explains the
2:54:45higher ATP yield, has a greater number
2:54:46of hydrogen atoms. So basically, I don't
2:54:50know if you guys have seen those awesome
2:54:51animations, but the human body as like a
2:54:53turbine system where it just shuttles
2:54:54these hydrononeium ions to make ATP.
2:54:57That's pretty much how it works inside
2:54:58of your cells. And so more hydrogen
2:55:00atoms just means that there's a molecule
2:55:02that is more reduced. So it can donate
2:55:04more electrons to NAD+ and FAD also to
2:55:08make more NADH and FADH2. That causes
2:55:10more ATP for oxidative phosphorilation.
2:55:13And that is why fatty acids which have a
2:55:15very it's a very hydrogen-rich molecule
2:55:18yield more ATP than carbon you know than
2:55:20carbs or alcohol right does that make
2:55:22sense we have all these hydrogens right
2:55:24so it's like the turbine can really get
2:55:25going with those fatty acids it's not
2:55:27like the aldahhides or the keto stuff
2:55:29that's already partially oxidized right
2:55:30so you have fewer electrons that you
2:55:32give up it's not going to be oxygen
2:55:33atoms right it's not oxygen atoms
2:55:35because more oxygen means more oxidized
2:55:38and so you have less potential for that
2:55:39ATP generation the amino groups don't
2:55:42drive a lot electron yield. Nitrogen has
2:55:44to be removed first. The amino groups
2:55:46have to literally go through the ura
2:55:48cycle before the ATP can be harvested.
2:55:50So here's some explanation. Hydroxal
2:55:52groups partially oxidized. Less hydrogen
2:55:55available. The carbonial have already
2:55:56been oxidized. They already lost their
2:55:58electrons. Peptides nitrogen containing.
2:56:01So it's all about those hydrogen atoms.
2:56:04Oh yeah. All right. This is a great
2:56:06question. And see if you can get it just
2:56:08only based on the description alone.
2:56:1020-year-old college student urgent care.
2:56:12Acute chest pain, shortness of breath
2:56:13after playing basketball, denied cough,
2:56:15fever, trauma. He has a history of
2:56:17asthma with albuterol. He's anxious to
2:56:19hypnic vitals are 98.6. His trachea is
2:56:22midline and oscultation breath sounds
2:56:24are decreased on the right side of his
2:56:26body. Percussion says hyper resonance
2:56:28over the same area. All right, what's
2:56:29the finding? The answer is going to be
2:56:31decreased breath sounds on the right. I
2:56:33know it already said that, but the point
2:56:35here is to identify and describe
2:56:37spontaneous pneumthorax. If you have a
2:56:39young male with asthma and thin body
2:56:41habitus, they might have a ruptured
2:56:42little bleb there and hyper resonance
2:56:44and decreased breath sounds shows you
2:56:46that you have some air in that plural
2:56:47space. So there's primary spontaneous
2:56:50pneumthorax that's a rupture of the
2:56:52apical subplural blebs usually in tall
2:56:55thin males when they're exerting
2:56:56themselves. Tension pneumthorax will
2:56:59also add the tracheal deviation JVD and
2:57:02severe hypotension and for that you need
2:57:04an emergency needle decompression. So
2:57:06pneumothorax right pneumothorax you
2:57:09think of the P for popped lung you have
2:57:11abs and breath sounds hyper resonant
2:57:13percussion and sudden chest pain these
2:57:16are good to know too increased tactile
2:57:17fematis pneumonia but is decreased
2:57:20because of air insulation crackles lung
2:57:22disease diffuse wheezing would be an
2:57:24asthma bronchial breast sounds left apex
2:57:27would be consolidation there's about one
2:57:29in 20,000 healthy males experiences this
2:57:31but yeah somebody's got like the chest
2:57:33pain shortness of breath all of a sudden
2:57:34an x-ray shows a left pneumothorax A
2:57:36left pneumthorax, by the way, would just
2:57:38mean that there's air in the plural
2:57:40space. And so in pneumothorax, the lung
2:57:42collapses and you hear like very little
2:57:44or no breath sounds on that particular
2:57:46side. And the chest also sound it sounds
2:57:48kind of like hyper resonance and like
2:57:50hollow whenever you tap it. Crackles
2:57:52tell you about pneumonia, fluid,
2:57:54fibrosis. Wheezes tell you about asthma
2:57:57and run is mucus in the airways. So
2:57:59pneumothorax is the collapsed lung
2:58:01causes decreased breath sounds on the
2:58:03affected side. So really just to drive
2:58:05this home, what about like a normal
2:58:07pneumthorax? Well, a normal pneumthorax
2:58:09air gets into the plural space and the
2:58:12lung on that side collapses. So pressure
2:58:14is inside that plural space and it
2:58:16starts to equal the atmospheric
2:58:18pressure. It's not building, right? And
2:58:20there's no tracheal deviation in a
2:58:21normal pneumthorax or there's like a
2:58:23really mild that's like toward the
2:58:25collapse, but don't worry about that.
2:58:27That's only if there's volume loss like
2:58:28in lectus tension pneumthorax. That's
2:58:31where you have that high pressure.
2:58:33Percussions hyper resonant just like in
2:58:35pneumothorax. Breath sounds are
2:58:36decreased or absent but the trachea
2:58:38deviates away from the affected side
2:58:40because of that pressure pushing the
2:58:41medastinum. Adalcttois is the lung
2:58:44collapse because of that obstruction. So
2:58:46usually in adaltoysis it's like a mucus
2:58:48plug or maybe have like some sort of a
2:58:50tumor and the breath sounds decrease on
2:58:52that affected side. The percussion is
2:58:53dull. So the trachea deviates toward the
2:58:55affected side. The volume loss pulls it
2:58:57over. Plural eusion is where fluid
2:58:59collects in the plural space there. The
2:59:01breath sounds are going to decrease for
2:59:03a plural eusion. It's going to be dull
2:59:05in the trachea has a small eusion,
2:59:06usually none. A large eusion, it can
2:59:08deviate away cuz like the fluid
2:59:09literally pushes it out. And the only
2:59:10other thing we haven't really covered is
2:59:12consolidation. For instance, pneumonia
2:59:14and that's the avoli that are filled
2:59:15with pus or fluid. The breath sounds
2:59:17there, bronchial, crackles, zagophony,
2:59:20percussions, dull, and the trachea stays
2:59:21midline there. So just in general I
2:59:24think what you should remember is that
2:59:26pressure pushes right tensionthorax
2:59:28large diffusion the trachea goes away
2:59:31volume decrease like adalcttois the
2:59:33trachea goes toward you and then
2:59:34regarding like the breath sounds
2:59:36percussion and all that stuff in the
2:59:38pneumothorax you have air in the plural
2:59:39space right and so the breath sounds are
2:59:41going to be decreased but the percussion
2:59:43is going to be hyper resonant hollow and
2:59:45the trachea is simple midline you know
2:59:48nothing but if there's tension then it
2:59:50deviates away so it's numoththorax for
2:59:52you breast The sounds decrease,
2:59:53percussion's hyper resonant. Adeltis has
2:59:55a collapsed lung and there you have the
2:59:57breath sounds decrease there. The
2:59:59percussion is dull. There's no air and
3:00:01the trachea is toward the affected side.
3:00:03Plural eusion. You have fluid in the
3:00:04plural space. So the breath sounds are
3:00:06decreased. You have that that dull kind
3:00:08of percussion stuff and it's away from
3:00:11that eusion. If it's a plural eusion
3:00:12fluid, if there's like a lot of fluid
3:00:14pushing it out of the way, breath sounds
3:00:15for consolidation would be bronchial,
3:00:17maybe some crackles, increased femitus
3:00:20for consolidation. Percussion's dull and
3:00:22the trachea stays midline. So remember
3:00:24air is hyper resonant and you have
3:00:26decreased sounds. Fluid fusion
3:00:28consolidation atisis would be dull and
3:00:30then pressure pushes trachea away and
3:00:32volume pulls it toward you pulls it
3:00:35toward the affected side. All right,
3:00:36that was 100 to 110. So like and
3:00:39subscribe if this was helpful. We'll see
3:00:41you guys in the next video. Hello
3:00:42everybody, welcome back. This is my
3:00:44original question 111. A 59-year-old man
3:00:47with a 10-year history of type two
3:00:48diabetes and hypertension presents with
3:00:51worsening fatigue diffused bone pain. He
3:00:52reports muscle cramps, paritis on his
3:00:54lower legs. He's taking leinipril and
3:00:56insulin. Lab values, low calcium, high
3:00:59phosphate. H is elevated. Gradin is
3:01:01elevated. Normal 25 hydroxy vitamin D
3:01:04and low 125. What explains these
3:01:06symptoms? All right, so this is chronic
3:01:08kidney disease secondary
3:01:09hyperarathyroidism. Basically what you
3:01:11look out for in this one is
3:01:12hypocalcemia, hyperphosphatia because
3:01:15you can't get rid of it. Why? Because
3:01:16your kidneys aren't working even though
3:01:18you have low calcium and phosphate. And
3:01:20what happens here is this is chronic
3:01:21kidney disease. So you have decreased
3:01:24GFR and that causes your phosphate to be
3:01:27retained which then leads to
3:01:28hypocalcemia and that's where the PTH
3:01:31starts to rise. So it can help you with
3:01:32your hypocalcemia. So you get that
3:01:34chronic kidney disease phosphate
3:01:36retention. the phosphate retention binds
3:01:38the serum calcium. And if you can't
3:01:39activate vitamin D, that makes this
3:01:41hypocalcemia problem even worse. So low
3:01:43calcium, high PTH and low activated
3:01:46vitamin D. All right, there's the
3:01:47explanation. In metastatic bone lesions,
3:01:49you'd see hypercalcemia. In oima, you'd
3:01:52see a vitamin D deficiency. Hypo would
3:01:54have low. In primary has high calcium
3:01:56are also going to develop bone
3:01:58abnormalities over time. And that's
3:02:00because the kidneys stop doing their
3:02:01job. They stop converting vitamin D to
3:02:03its active form. And without the active
3:02:05form, the 125 form, you can't uptake a
3:02:08sufficient amount of that calcium. All
3:02:09right. Now, for this next question, I'd
3:02:10like for you to take a look at this
3:02:12drawing that I've done and tell me what
3:02:13is the condition associated with this
3:02:15drawing. Now, I know I'm not the best
3:02:16artist, but it's going to be associated
3:02:18with this question. A young boy, it
3:02:20could be anything. Presents with
3:02:21progressive disysmia and dry cough for
3:02:23the past 3 days. Shannon renal
3:02:25transplantation 8 weeks ago and has been
3:02:27untacy, micopenolate, and predazone.
3:02:30Temperature is at 101.8.
3:02:32Respiratory rate is at 28 and the chest
3:02:35exam shows bilateral crackles. Chest
3:02:37radiography shows diffuse interstitial
3:02:39infiltrates. Bronchiola lavage reveals
3:02:41large monuclear cells with basophilic
3:02:43nuclear inclusions. PCR detects DNA
3:02:46virus. Which immune cell dysfunction
3:02:48most likely contributed to this
3:02:49condition. All right, we know it's a DNA
3:02:51virus and in fact this is going to be a
3:02:53latent herpes virus. This is H HV5 which
3:02:57is a correct answer. So CMV pneumonia is
3:02:59an opportunistic T- cell suppressed
3:03:01related infection after a transplant. So
3:03:03the CMV infected cells present viral
3:03:06antigens via the MHC1 complex and those
3:03:10are recognized by the CD8 positive tea
3:03:13cells and that leads to the perforin
3:03:14granzyme mediated killing the prevention
3:03:16of viral replication and so you often
3:03:19see this with T- cell suppression and
3:03:20postrplant amunosuppressive therapy in
3:03:23the hisytologology you see the ally
3:03:24inclusions. So yeah, CMV is T- cell
3:03:26mediated cenaphils is against the
3:03:28helmets natural killer cells CMV evades
3:03:32adaptive T- cell immunity. All right,
3:03:34here are the associations. Transplants
3:03:36CD4 below 50 graph versus host disease.
3:03:39It's a DNA virus. You suppress those CD8
3:03:41positive tea cells and that can cause
3:03:43reactivation in the lungs causing avular
3:03:45damage. Treatment is gainy valycllir.
3:03:48All right, next question. Look, that's
3:03:50you right there. A researcher is
3:03:52studying the binding properties of novel
3:03:55tetromeic protein to its signaling
3:03:56molecule. She constructs a graph of lian
3:03:59concentration and notices the binding is
3:04:00sigmoidal. That means positive
3:04:02cooperativity among the binding sites.
3:04:04So the receptor lian binding curve has a
3:04:06sigmoidal shape with a steep increase in
3:04:08the binding over the narrow range of the
3:04:10hormone concentrations. All right. So
3:04:11this is just a question about
3:04:12cooperivity and this graph right here is
3:04:15going to be a cooperative graph. The
3:04:16sigmoidal shape whereas this one is not
3:04:18the cooperative graph. Cooperative
3:04:20sigmoidal. That's all we need to know.
3:04:21All right. For this next question, we
3:04:22have a 16-year-old boy. Cystic fibrosis
3:04:24comes to the clinic. Has multiple
3:04:26pulmonary exacerbations the past six
3:04:27months. FV1 is 40 45% predicted. BMI
3:04:3110th percentile. He skips nebulizer
3:04:34treatments because they take too long.
3:04:36He's alert and cooperative. What should
3:04:38be the initial response? It should be
3:04:39acknowledge. Acknowledge the challenges
3:04:41of adhering to a time-consuming regimen.
3:04:43So your steps should always be you
3:04:45acknowledge, you validate, and then you
3:04:47problem solve later. So first you have
3:04:49to acknowledge then later you solve
3:04:50this. Always acknowledge and try to
3:04:52understand what makes the adherence
3:04:54difficult. You have to acknowledge the
3:04:55frustration and explore the barriers and
3:04:57then you use motivational interviewing
3:04:59where you express empathy. You roll with
3:05:01the resistance and you support
3:05:02self-efficacy. And you have to first
3:05:04empathize. You have to say hey you know
3:05:06I know it's hard to miss these insulin
3:05:08injections. First you have to empathize
3:05:10and then you have to validate and then
3:05:12you can solve the problem. Explore those
3:05:13barriers. Acknowledge that it's
3:05:15challenging. For the next question, we
3:05:16have a 45year-old Vietnamese woman,
3:05:18progressive nasal obstruction and
3:05:20intermittent epistaxis. Epistaxis over
3:05:22the last 3 months. She's noticed a
3:05:24fullness of the left side of her neck.
3:05:26She's got a firm non-tender mass in the
3:05:27left posterior cervical chain.
3:05:29Fangiocopy reveals a frial mass in the
3:05:31lateral wall of the nasoperings. She's
3:05:33got Epstein's bar. What is the most
3:05:35likely diagnosis? Nasophrenial
3:05:36carcinoma. It's just textbook right
3:05:38there. So nasophrenial carcinoma is a
3:05:40malignancy that arises from the
3:05:42epithelium of the nasoperings. And
3:05:43that's because there's this this FOSA
3:05:45there's the recess in the lateral
3:05:47nasoparangial wall and this is really
3:05:49associated with EBV especially if you
3:05:51see somebody from southern Asia,
3:05:52Southeast Asia and North Africa and this
3:05:55presents with a nonquamus carcinoma but
3:05:58there are also going to be some
3:05:59keratinizing subtypes as well. The thing
3:06:01to look out for is positive staining on
3:06:03Epstein's bar virus, nuclear antigens.
3:06:05And so the symptoms are going to be
3:06:06nasal symptoms, right? Congestion,
3:06:08epistaxis, ear symptoms, the Asian tube
3:06:11obstruction, conductive hearing loss,
3:06:13cranial nerve involvement as well. You
3:06:15can see, you know, horarsseness,
3:06:16dysphasia, see some cranial nerve 9 and
3:06:1810 action, cervical lympadnopathy as
3:06:20well. And to treat this, we use
3:06:23radiation and chemotherapy. But this is
3:06:25linked EBV is linked to nasophrenial
3:06:27carcinoma, especially in Asian
3:06:29populations. And this is present with
3:06:30epistaxis, nasal obstruction and
3:06:32cervical node involvement. Now let's
3:06:34talk about what this is not because
3:06:36that's also equally important. This is
3:06:38not diffuse large bell lymphoma. While
3:06:40EBV can be associated with diffuse large
3:06:42cell especially in imunocmpromised
3:06:44patients, it is a lymphoid neoplasm not
3:06:46an epithelial carcinoma. So this patient
3:06:48has a keratin positive tumor and that
3:06:50means it's epithelial origin and so it's
3:06:52not going to be a lymphoma and so it
3:06:53can't be diffused large cell lymphoma.
3:06:55But you should be thinking of you know
3:06:58large B cell lymphoma and
3:06:59imunocmpromised patients in lymphoid
3:07:01neoplasm but not epithelial carcinoma.
3:07:03That's why it's not diffused B cell. Why
3:07:04is it not HPV like oropharrenial
3:07:06squamous cell carcinoma HPV? Well HPV is
3:07:09associated with oropharrenial cancers
3:07:11that's like the tonsils the base of the
3:07:13tongue and not the nasoparangial and
3:07:15those tumors also are a little bit
3:07:16different. and they stain P16 positive
3:07:18not EBNA positive and it's more common
3:07:21in like western countries okay so not it
3:07:23squamous cell carcinoma of the nasal
3:07:25vestibial that's located in the external
3:07:27ns and unrelated to HPV so basically the
3:07:32high yield recap for this is you got
3:07:33somebody from Southeast Asia with a
3:07:34nasal obstruction hearing loss and
3:07:36lympadnopathy then it's going to be a
3:07:37nasoprangial carcinoma likely epste
3:07:39virus you're going to see keratin and
3:07:41that shows you that it's an epithelial
3:07:43origin and epsenar antigens like the
3:07:45ebna a positivity that means you have
3:07:48epsin spar virus involvement and that
3:07:50makes nofrangingial carcinoma the best
3:07:52answer. So that is the recap on this
3:07:54question. All right this question
3:07:55typically going to be an older patient.
3:07:5761 former pianist presents with a
3:08:00progressive stiffness and aching of her
3:08:01right thumb and wrist that began over
3:08:03the past 5 months. The pain is
3:08:05aggravated by playing and relieved by
3:08:06rest. That should make you already think
3:08:08of osteoarthritis. So piano, you know,
3:08:10it could be tennis coaching, it could be
3:08:12a lot of things. repetitive joint use.
3:08:13It's typically in elderly patients, you
3:08:16know, maybe late 50s, early 60s.
3:08:18Osteoarthritis is the degenerative joint
3:08:20disease that's caused by mechanical wear
3:08:22and tear. You literally break down that
3:08:24articular cartilage and that causes the
3:08:26formation of subcondrial sclerosis,
3:08:28osteophytes, and joint space narrowing.
3:08:30So look out for that repetitive stress.
3:08:32Senovial findings are going to be
3:08:34non-inflammatory
3:08:35and also less than 2k white blood cell.
3:08:38Clear fluid, normal glucose, no
3:08:40crystals. So osteoarthritis is a
3:08:42mechanical joint disease. Morning
3:08:43stiffness less than 30 minutes improves
3:08:44with use. Synovial fluid is
3:08:46non-inflammatory. So there's pseudo gout
3:08:48would be the deposition of calcium
3:08:50pyrophosphate dehydr dehydrate in the
3:08:52joint cartilage. That's pseudo gout. And
3:08:54that would typically be with larger
3:08:55joints, you know, like the knee, wrist,
3:08:57shoulder. And there you would have
3:08:59positively brentent romboid shaped
3:09:02crystals. Romboid shaped crystals. If
3:09:04the answer were something like the
3:09:06deposition of calcium pyrophosphate
3:09:08positively bifringent romboid shaped
3:09:10crystals. So that's pseudogout. Also
3:09:12immune complex mediated synovial
3:09:14inflammation is seen in rheumatoid
3:09:16arthritis and other autoimmune
3:09:17inflammatory arthritities. Rheumatoid
3:09:19arthritis is symmetrical and
3:09:21polyarticular. It also has morning
3:09:23stiffness and inflammatory synovial
3:09:25fluid. So you have a lot of white blood
3:09:27cells in the fluid. It's not going to be
3:09:28an acute bacterial infection in the
3:09:30joint space either. Here we have joint
3:09:31space narrowing. But if they were to say
3:09:33there's like some infection in the joint
3:09:35space, then that could be septic
3:09:37arthritis and that has acute onset,
3:09:39severe pain, arythemma, warmth, perulent
3:09:42synovial fluid, white blood cells are
3:09:43going to be galore, just like 50k of
3:09:45them just all around. And if it said
3:09:47monosodium urate, then that's just gout.
3:09:49That'd be sudden painful swollen joint
3:09:51in the first MTP. So you'd have the
3:09:53needle-shaped negatively by fringent if
3:09:55it were gout. All right, so that's how
3:09:56to distinguish between all of these
3:09:58different conditions here. You can read
3:09:59about them here. All right, next we have
3:10:01a 28-year-old man going to the clinic
3:10:02with four months of persistent diarrhea.
3:10:04The stool has blood in it, constant
3:10:06feeling of needing to defecate even
3:10:07after using the toilet. Colonoscopy
3:10:09shows mucosal inflammation from the
3:10:11rectum to the splenic flexure.
3:10:13Cryptabsises and distortion. Which of
3:10:15the following complications is this
3:10:17patient most at risk for developing? The
3:10:19answer is colorectal carcinoma because
3:10:20this is ulcerative colitis. So the
3:10:22things to look out for are bloody
3:10:24diarrhea, tenism which is the continual
3:10:26reoccurrent need to evacuate the bowels,
3:10:29left lower quadrant pain, athemma no
3:10:31dosum and also with UC you have the
3:10:33fryable mucosa and continuous
3:10:36involvement starting at the rectum and
3:10:38the biopsy shows crypt abscesses and
3:10:40mucosa sub mucosa limited inflammation.
3:10:43So what happens here is it starts in the
3:10:44rectum and it extends proximally in a
3:10:47continuous fashion and so inflammation
3:10:48is limited to the mucosa and the sub
3:10:50mucosa. It's not transmural. The biopsy
3:10:52has crypt abscesses. There's not skip
3:10:55lesions or granulomaas. So that's
3:10:57ulcerative of colitis, mucosal,
3:10:58submucosal, inflammation, continuous
3:11:00involvement. Always rectal involvement.
3:11:02Every single time going to have rectal.
3:11:04That's why we wanted to mention the
3:11:06tennis in this question. Always rectal
3:11:08involvement. Crypt abscesses, no
3:11:10granulomaas. There's a risk of
3:11:12colorectal carcinoma and it's associated
3:11:14with primary sclerosinitis
3:11:16and piana. All right. Now, some other
3:11:18answer choices that they could have
3:11:19given you are like transmural
3:11:21inflammation with granuloma formation.
3:11:23That would be Crohn's disease cuz
3:11:25Crohn's disease is a different beast,
3:11:27but there are a lot of similarities.
3:11:28Crohn's has skip lesions. There's also
3:11:31cobblestone mucosa and it can affect any
3:11:34part of the GI tract, any part. This is
3:11:36also associated with fistula strictures
3:11:38and non-caseing granulomus. Now they're
3:11:41also going to try to get you on
3:11:42diverticulitis and that's common in
3:11:44elderly adults and you would see left
3:11:46lower quadrant pain there. You'd also
3:11:48you would not have bloody diarrhea and
3:11:50there's also not going to be diffuse
3:11:51mucosal inflammation on colonoscopy and
3:11:53they could also try to get you on
3:11:55another question with cediff and that is
3:11:57typically after antibiotic use you have
3:11:59watery diarrhea there andoscopy shows a
3:12:01yellow white pseuda membrane that's not
3:12:03continuous mucos ulceration they could
3:12:05also try to ask about eskeeia you know
3:12:07acute messenteric eskemia usually it'll
3:12:09be like an SMA occlusion something like
3:12:11that that's associated with sudden onset
3:12:13severe pain lactic acidosis and also
3:12:15risk factors like atrial
3:12:17fibrillation, but this person just has
3:12:19ulcerative colitis, just a chronic
3:12:21disease causing bloody diarrhea and
3:12:22inflammation starting in the rectum.
3:12:23That's what you need to know about
3:12:24ulcerative colitis. The inflammation is
3:12:26limited to just the surface layers of
3:12:28the colon and it spreads in a continuous
3:12:29path, continuous, unlike Crohn's
3:12:31disease, which just skips all around and
3:12:33then it digs super deep into the bell
3:12:35wall. All right, for the next question,
3:12:36we have a 46-year-old man. He's got
3:12:38bipolar disorder treated with lithium.
3:12:41He's drinking tons of water. And what we
3:12:43know about lithium is that it actually
3:12:45impairs the ability of that collecting
3:12:47duct to reclaim the water because it
3:12:49stops that ADH. So what describes the
3:12:51tubular fluid tonicity relative to the
3:12:54plasma? Let's talk about the
3:12:55pathophysiology here. Lithium therapy
3:12:57for bipolar disorders disrupts the V2
3:13:00channels and so you get hyperetreia and
3:13:02increased serum osmolality. Why? Because
3:13:05that water leaves. The water is gone. It
3:13:08can't be re-uptaken by those V2 channels
3:13:09anymore. So the lithium inhibits the V2
3:13:12receptor signaling. The collecting duct
3:13:14fails to absorb the water and now the
3:13:16urine is just full of water. So the
3:13:19medelary gradient gets washed out and so
3:13:21then you just lose the ability to
3:13:22concentrate at all. And hypermreia,
3:13:25polyypipssia, polyura, you have no
3:13:26improvement even after you give him
3:13:28desmopressin. Now we have to know what's
3:13:29happening in the proximal convoluted
3:13:31tubule and that's the segment that
3:13:32reabsorbs 65% of the filtered sodium and
3:13:36water. That happens isotonically because
3:13:38both solutes and the water are
3:13:40reabsorbed proportionally. The tubular
3:13:41fluid osmolality remains isotonic and
3:13:43that's always true. It's true in every
3:13:45condition even nephroenic diabetes and
3:13:47typus. And the DCT the distal convoluted
3:13:49tubule is impermeable to water but it
3:13:51actively reabsorbs sodium and so the
3:13:53tubular fluid becomes dilute or
3:13:55hypotonic as the solids are removed. But
3:13:57in normal and DI patients the segment
3:14:00will be lowering the tubular osmolality.
3:14:03So you'll see hypotenicity there and the
3:14:05medularary collecting duct is at the end
3:14:07and in healthy patients that's the site
3:14:09of the ADH action and that's where water
3:14:11is reabsorbed through the aquaporins but
3:14:13in nephrogenic DI aquaporn insertion
3:14:15will fail because of that lithium that
3:14:17interferes with the V2 receptor mediated
3:14:19camp signaling and so no water is
3:14:21absorbed and so this can be diluted and
3:14:22hypotonic even in the medula where the
3:14:24interstial osmolality is high. So even
3:14:26though you have high plasma osmolality,
3:14:28the urine is dilute because of the
3:14:29collecting ducts and desmarapressin
3:14:31fails to concentrate whereas it would
3:14:33really help if this were just central
3:14:35DI. So without that camp aquaporins
3:14:37can't work. Proximal tubule is going to
3:14:39be normal but the collecting duct is
3:14:41hypotonic because these guys are
3:14:42watertight and then you can't absorb it
3:14:44at the end. So it's also hypotonic as
3:14:46well. All right, there are the kidneys.
3:14:47All right, here's the next question. We
3:14:48have a 43-year-old man admitted with a
3:14:50high-grade fever, altered mental status
3:14:52and painful swollen right thigh. had
3:14:53minor surgery. 104 super high fever.
3:14:56Knee with paprepitus. He is abundant.
3:14:59Withdrawals from painful stimuli. Here
3:15:01are the labs. What describes the
3:15:02mechanism? All right. So for this
3:15:04question, we have to know what's
3:15:05happening. And this is toxic shock
3:15:07syndrome. How do we know? We got a
3:15:09fever, hypotension, multiple organ
3:15:12dysfunction, so renal and hypatic. And
3:15:14there's diffuse arithmatic rash after
3:15:16nasal surgery. And that's a known risk
3:15:18factor for toxic shock. And that's
3:15:20because of the nasal packing that's
3:15:22colonized by stafloccusarius. So toxic
3:15:25shock is caused by stafloccusarius via
3:15:27the tssts1 pathway or streptococcus
3:15:30piogynous through exotoxin A or C. And
3:15:32they both share the same mechanism for
3:15:34toxic shock. And the mechanism is you
3:15:36have that toxic shock syndrome toxin T
3:15:39SST1 that binds non-specifically to the
3:15:43T receptors and the MHC class 2
3:15:46molecules on the antigen presenting
3:15:49cells. It bypasses the normal antigen
3:15:51specificity and it activates 20% of the
3:15:53T- cells at once. And so that's a huge,
3:15:55as you can imagine, cytoine release. And
3:15:57so now you're just swarmed in IL2, IFN
3:16:00gamma from T- cells, IL1, TF alpha from
3:16:03macrofasages, and that leads to a
3:16:04cytoine storm. So you have shock, organ
3:16:07failure, and rash. So that's our answer
3:16:09is C. Trap answers caspace, cleavage to
3:16:12apoptosis. Definitely not toxic shock.
3:16:14That's like a viral bacterial
3:16:16manipulation. Inactivation of EF2 that's
3:16:18dtheria and sedamonus leithin
3:16:20hydrarolysis is clustrdian perfenens
3:16:22alpha toxin serum proteas disrupting the
3:16:25junctions is exfoliative tox of
3:16:27stafarius and scalded skin syndrome that
3:16:29is exfoliative toxin in stafarius and
3:16:32scalded skin syndrome. So yep it's the
3:16:35bacteria that makes your immune system
3:16:37go into overdrive. All right, for the
3:16:38next question, we got a little baby.
3:16:404-day old infant presents with vomiting,
3:16:42lethargy, poor feeding. Examination
3:16:44reveals signs of dehydration and
3:16:46ambiguous genitalia. Sodium is 122,
3:16:48potassium 6.5. So that's a low sodium,
3:16:50high potassium, glucose of 48. Oh,
3:16:53genetically female. So this is
3:16:55congenital adrenal hyperplasia. And they
3:16:57give us the 17 is markedly elevated as
3:16:59well. And that's diagnostic for it. 11
3:17:01beta hydroxilase, that'd be hypertension
3:17:03due to excess. 11 deoxxycortico 11 d 11
3:17:07deoxycorticosterone
3:17:09but this patient is hypotensive and so
3:17:12that can't be the answer so it's going
3:17:13to be 21 hydroxilase deficiency causing
3:17:16that elevated 17 aromatase that's
3:17:19involved in the maternal verilization
3:17:21during pregnancy does not cause salt
3:17:22wasting at all 17 alpha hydroxilase that
3:17:25would cause hypertension and sexual
3:17:27infantilism and this guy right here is
3:17:28super rare probably won't see it on test
3:17:30day but the takeaway for this question
3:17:32is that 21 hydroxilate
3:17:34is required to make cortisol and
3:17:37aldoststerone and so deficiency leads to
3:17:39lower cortisol, lower aldoststerone and
3:17:41increased antigens. So you get the
3:17:43viralization in the XX infants and 21
3:17:46hydroxilase deficiency is the most
3:17:48common cause of congenital adrenal
3:17:50hyperplasia and it affects newborns with
3:17:52ambiguous genitalia salt wasting crisis.
3:17:53So hyperutriia, hypercalcemia and
3:17:56dehydration and also elevated 17 hydroxy
3:17:59progesterone. You give him
3:17:59gluccocorticoids and mineral corticoid
3:18:02replacement. All right. In this
3:18:03question, we have a 10-year-old boy
3:18:04brought to the pediatric clinic for
3:18:06evaluation of skin nodules and fatigue
3:18:08on exertion. His father died at 36 from
3:18:10myioardial inffection. Photoscopic exam
3:18:13shows gray white deposits near the
3:18:15corneal margins. Lab shows total
3:18:17cholesterol 620 LDL 540. All right. So,
3:18:20what's happening here? You can see these
3:18:23firm yellow nodules, these tendons,
3:18:25anthomas. He might also have some you
3:18:27have some corial problems some corial
3:18:29arcus an elevated LDL cholesterol. These
3:18:32are hallmarks of familial hyper
3:18:34cholesteria and this is due to a
3:18:35defective or absent LDL receptor
3:18:37mediated endoccytosis. So you have high
3:18:39LDL right like look at that that's
3:18:41extremely high tendons anthoma so like
3:18:44the Achilles and extensor extensor
3:18:46tendons and lipid deposition as well can
3:18:48occur in the cornea and premature
3:18:50cardiovascular symptoms so like chest
3:18:52pain disysmia things like that and so
3:18:54the answer is going to be the impaired
3:18:55clin dependent LDL receptor endoccytosis
3:18:58and so the pathophysiology of familial
3:19:00hyper cholesterol anemia familial hyper
3:19:02cholesterol anemia is a mutation of the
3:19:05LDL receptor or on the apo 00 or the
3:19:08PCK9 those proteins and the LDL
3:19:11receptors on the hpatocytes bind the LDL
3:19:13to internalize it through the receptor
3:19:14mediated endoccytosis and that relies on
3:19:16the the clatherine coded pits. So yeah,
3:19:19if you see somebody who has like a heart
3:19:20attack before they have their driver's
3:19:22license, then they probably have FH.
3:19:23Look for tendons and coronial arcus and
3:19:26LDL levels above 500. Just a dead
3:19:28giveaway and then you have to know the
3:19:29mechanism. Cabulin deficiency
3:19:31non-clatherine endoccytosis not LDL. So
3:19:33that's why A is wrong. These are the
3:19:35mutations they're different diseases.
3:19:37Apo C2 would raise triglycerides because
3:19:40you can't clear the kyomicrons and snare
3:19:42defect affects the vesicle fusion. All
3:19:45right, hopefully you guys found this
3:19:46helpful. If you did, please consider
3:19:48liking and subscribing and we'll see you
3:19:49guys in the next video. Hello everybody.
3:19:51Welcome back. Look, I just figured out
3:19:53how to use this microphone. This is MBME
3:19:5529. I've created original questions that
3:19:57cover topics that I believe are
3:19:58important for you to have mastered by
3:20:00the time you finish this exam. So, here
3:20:02we go. Our first question involves a
3:20:0466-year-old man. It could also be a
3:20:06female, hence our demographic photo
3:20:08here. With chronic kidney disease and
3:20:09hypertension presents with sudden onset
3:20:11left ankle pain and swelling, he has
3:20:13difficulty bearing weight and reports
3:20:14chills and fatigue. Temperature is
3:20:15101.8. 8 on examination left ankle is
3:20:18warm ariththmatus and tender novial
3:20:20fluid white blood cell count of 78k 94%
3:20:23neutrfils gram shows abundant neutrfils
3:20:25been benacteria which the following is
3:20:26most likely the cause of the patient
3:20:28symptoms okay so in this type of patient
3:20:30you're going to see typically it's some
3:20:32sort of like a sudden fever might have
3:20:35like a very painful knee and then maybe
3:20:37also diabetes something like that all
3:20:40these things are pointing to infection
3:20:42risk and then you look at the joint
3:20:43fluid and what do we see white blood
3:20:45cell count that's pretty high in
3:20:46neutrfils, septic arthritis, and also
3:20:49they could tell you that, hey, there's
3:20:50no there no crystals, then it's not gout
3:20:52or pseudogout. And also, they'll mention
3:20:54that it's cloudy. They'll give you some
3:20:55detractor answers. For instance, they'll
3:20:57say, oh, is it gout? Well, no, that has
3:20:59your castic crystals and fewer white
3:21:00blood cells. Is it pseudogout? No,
3:21:03pseudo gout would have calcium crystals
3:21:05and there's none of that. What about
3:21:07DVT? Well, that would cause a leg
3:21:09swelling, not that hot red joint. Okay,
3:21:12so that's the way to think about this
3:21:13question. The cause is septic arthritis.
3:21:15That's the cause. Calcium pyroofhosphate
3:21:17is pseudogramboid crystals.
3:21:19Arythemodosum
3:21:21which are the nodules in the shins. Skin
3:21:23manifestation reactive arthritis is post
3:21:25infectious and it' be asymmetric
3:21:27oligoarthritis after some sort of an
3:21:29infection. Not going to be as acute
3:21:31arthrosis, bloody aspirate. So yeah,
3:21:34septic arthritis can actually just
3:21:35destroy a joint in like 48 hours.
3:21:37They'll present with acute red hot joint
3:21:40pain and also some systemic signs like
3:21:42fever. In our next question, we have a
3:21:449-month old boy from Middle Eastern
3:21:45descent brought to the clinic for palar
3:21:48poor feeding hpatosplenomegaly. Lab
3:21:50testing reveals a hemoglobin level of
3:21:525.8. Now, this could be a male, could be
3:21:54a female. Perhaps smear shows microitic
3:21:57hypocchromic RBCs with numerous
3:21:59nucleated red cells. Genetic testing
3:22:01confirms a mutation affecting intron
3:22:03exxon splicing of both beta globin
3:22:06alles. What explains the anemia? It's
3:22:08the accumulation of unpaired alpha
3:22:10globin chains. So normal adult
3:22:12hemoglobin so HPA has two alpha and also
3:22:16two beta chains and inthalmia major
3:22:19mutations like splice site defects will
3:22:22greatly reduce the betalobin production
3:22:24and so alphaglobin is still going to be
3:22:26made normally and so there's an
3:22:27imbalance there's too many there are too
3:22:29many alpha chains and not enough beta
3:22:30chains and so extra alpha chains will
3:22:32clump together you'll get these alpha 4
3:22:35tetimer which are insoluble and they
3:22:37damage the red blood cells and they
3:22:38cause severe anemia so those would be
3:22:40increased
3:22:41Beta tetimer would be a feature of
3:22:43alphaalismia
3:22:45which makes sense because two alphas two
3:22:47betas is what's needed for adult
3:22:48hemoglobin and so the answer is the
3:22:50accumulation of the unpaired alpha
3:22:51chains that's what's happening here so
3:22:53yep it's betalcemia major gammoglobin
3:22:56tetimer would be barts and
3:22:59alphaththalmia lowo would be anemia of
3:23:02chronic disease deltaglobin here we
3:23:04should definitely just be thinking of
3:23:05like alpha beta for yourthalmas
3:23:08betalismia would have a decreased beta
3:23:10beta chains and so you have excess alpha
3:23:12chains. Alphaththalmia has decreased
3:23:14alpha chains so you have excess beta
3:23:15chains or you know your gamma tetramse
3:23:18thethalmia essentially denotes the
3:23:20deficiency is the way to think about
3:23:21that. Okay. Next we have a 27-year-old
3:23:23woman with a history of scutzoffective
3:23:25disorder brought to the emergency
3:23:26department due to confusion and muscle
3:23:27stiffness. This could also be you know a
3:23:29man, elderly man, elderly woman
3:23:32whatever. She recently started on
3:23:34respirone 4 days ago following an acute
3:23:37psychotic episode. After arrival, her
3:23:38temperature is 40° Celsius of 105. Holy
3:23:43Toledo muffins. That's high. Heart rate
3:23:45130. Physical exam reveals generalized
3:23:48muscle rigidity. Okay, so already I know
3:23:50that this is neurolleptic malignant
3:23:52syndrome because look at that fever. Oh
3:23:54my goodness. They took a dopamine
3:23:56blocking antisycchotic and now their
3:23:57fever is through the roof. Definitely
3:23:58neurolleptic malignant syndrome. So they
3:24:01probably started like yeah respirone
3:24:03could be halalodol like a high potency
3:24:06antiscychotic and now they have a super
3:24:08high fever muscle rigidity that lead
3:24:10pipidity is how it's commonly known so
3:24:12the answer is indeed C neurolyptic
3:24:14malignant syndrome after you have a
3:24:16dopamine blocking antiscychotic you get
3:24:19that muscle rigidity altered mental
3:24:20status they'll be disoriented they might
3:24:22be agitated they have autonomic
3:24:24instabilities ticardia labile BP
3:24:27increased CK the muscle breakdown from
3:24:29the rigidity will also take place. The
3:24:31mechanism of action is important to
3:24:33cause here is you have that antagonism
3:24:34of your D2 receptors. Your nigradal and
3:24:37your pathways are going to be blocked
3:24:39from antiscychotics like alipirol or
3:24:41spiritone. Nigradal blockade causes
3:24:43severe muscle rigidity that lead pipe
3:24:45rigidity and the hypothalamic blockade
3:24:48causes the loss of the dopamine
3:24:49regulation and autonomic instability and
3:24:51hyperothermia. So you have sustained
3:24:52rigidity, muscle breakdown and that
3:24:55increases your CK and rabdomiolysis. So
3:24:58first of all, how do we treat this? We
3:24:59have to stop the antisycchotic. You have
3:25:01to give supportive care, right?
3:25:02Hydration, cooling. Dantrine is going to
3:25:05inhibit the ryanodine receptors in the
3:25:07skeletal muscle, right? You got to
3:25:08inhibit those. But dantine and that
3:25:11would cause less calcium release and so
3:25:12less rigidity, less heat. Brocryptine,
3:25:15mantadine. These are dopamine agonists
3:25:18and they restore the dopamine signaling.
3:25:19Neurolctability syndrome is too much
3:25:21dopamine blockade, decrease dopamine
3:25:23activity, cause rigidity, fever, and
3:25:24autonomic dysfunction. That's what's
3:25:26going on. Serotonin syndrome, hyper
3:25:28reflexia clonus, malignant hypothermia,
3:25:30exposure to anesthetics, no surgical
3:25:33anesthesia history there, so it's not
3:25:34going to be malignant hypothermia. Tart
3:25:36of disynesia would be lip smacking
3:25:38coria, that stuff. And this is super
3:25:40important because it has a mortality
3:25:41rate of like 20% if it's untreated.
3:25:43Next, we have a 2-year-old girl with a
3:25:44denazine diaminas deficiency undergoing
3:25:47experimental gene therapy with an
3:25:49integrating retroviral vector. After
3:25:51initial improvement in immune function,
3:25:53she returns with persistent fevers,
3:25:54fatigue, cervical lympadnopathy.
3:25:56Peripheral blood smear reveals
3:25:58lymphoblast. Flowcytometry reveals T-
3:26:00cell markers. Kerotyping is normal, but
3:26:02molecular analysis reveals vector
3:26:04insertion upstream of the tal one gene.
3:26:06What explains the mechanism of her
3:26:08condition? Adenazine diamin deficiency.
3:26:10All right, so this is probably going to
3:26:11be a young kiddo boy, girl. We got some
3:26:14T- cell markers and vector insertion
3:26:16upstream of the gene. All right, so
3:26:18what's happened here? This is T- cell
3:26:20leukemia after gene therapy and this is
3:26:22a risk when retroviral vectors integrate
3:26:25near the enkco genes like tal one gene.
3:26:27So this is mechanism called insertional
3:26:29mutogenesis. You activate the ankco
3:26:31genes and it leads to clonal malignant
3:26:33transformation. And there are some
3:26:35things to watch out for for questions
3:26:37like this. What comes to mind should be
3:26:39you should be on your radar. You should
3:26:41be thinking about like p-53 because the
3:26:43p-53 deactivation that's common in tons
3:26:45of cancers but retroviral gene is going
3:26:48to be different. You could be thinking
3:26:49about PRB phosphorilation that's
3:26:51downstream cell cycle control. It's not
3:26:53caused by retroviral insertion. You
3:26:56should be thinking of other cancer
3:26:57associations. Maybe that 922
3:27:00Philadelphia chromosome for BCRL
3:27:04Philadelphia chromosome for CML other
3:27:06reverse transcription like you know P10
3:27:08is a tumor suppressor. But we're looking
3:27:10for what causes our leukemia. Here it's
3:27:12going to be integration of a trans gene
3:27:14and you're a pro a protoonco gene. And
3:27:17it's important if you have a a denazine
3:27:19diaminise deficiency then you've got
3:27:21skid, right? The boy in the bubble
3:27:22disease. It's an Xlink severe biona
3:27:25deficiency disorder. And so you're going
3:27:27to use retroviral gene therapy. So a
3:27:29virus carries a normal copy of the
3:27:32missing gene and it integrates into the
3:27:34child's bone marrow and the stem cells.
3:27:36Those are the cells that make the normal
3:27:37immune cells. And at first it's working,
3:27:39but then years later the child gets like
3:27:41T- cell leukemia. So the question that
3:27:43they're really asking is like, okay, how
3:27:45did this happen with the skittyw skin
3:27:46skid? They're asking what went wrong.
3:27:48Well, retroviruses don't choose where
3:27:50they insert the DNA. They just kind of
3:27:51integrate randomly into the host
3:27:52genomes. And so some unlucky ones, the
3:27:55virus inserts the DNA right next to an
3:27:57enco gene and that causes the enco gene
3:27:59to be turned on too strongly and then
3:28:01you get cell growth, which is cancer. So
3:28:03this is insertional mutagenesis. Now
3:28:06what you should know about p-53, PRB and
3:28:09also P10 is that these guys are tumor
3:28:13suppressor genes. So the mutations there
3:28:15would cause cancer not from retroviral
3:28:17insertion. So the Philadelphia
3:28:18chromosome, the BCRL CML, that's not
3:28:21related to gene therapy at all. But the
3:28:22big takeaway for this question is that
3:28:24retroviral gene therapies have risks.
3:28:26They can cause random integration and
3:28:28activation of anka genes. And if you
3:28:30activate your anka genes, then boom, you
3:28:31got leukemia. So that's what they're
3:28:32testing you on. All right. Okay,
3:28:33question 125. 65-year-old woman, history
3:28:36of type 2 diabetes and hypertension,
3:28:38presents of confusion, progressive
3:28:39fatigue over the last 3 days. Could be
3:28:41an elderly man as well. She missed her
3:28:43diialysis session early that week. Vital
3:28:45show heart rate of 98, T of 36° Celsius.
3:28:49She has perorbital and pedalma.
3:28:51Neurological exam shows us asteris.
3:28:53What's the cause of her disturbance
3:28:54here? And they give us a ton of labs.
3:28:56All right, so what's going on in these
3:28:58labs? Do they give us a pH? Oh, yeah,
3:29:00there it is. Okay. I was like, wow,
3:29:01where's the pH? 7.3. Okay, so that's
3:29:04that's low. So we're dealing with
3:29:05academia. ACO3 at 12. Okay, well that's
3:29:08low. So that's metabolic acidosis. PCCO2
3:29:12is at 25. That's also low. So that means
3:29:14the lungs are compensating with some
3:29:16hyperventilation. And now let's
3:29:17calculate that annion gap. And anytime
3:29:19you do the annion gap, it is the sodium
3:29:22minus all the negative stuff. So like
3:29:24chloride, bicarbonate. And we're going
3:29:26to get a pretty high annion gap when we
3:29:27do that. Normally it's like less than
3:29:2912. This is going to be pretty high. And
3:29:30so the causes of the inion gap elevated
3:29:33in gap metabolic acidosis are mud piles.
3:29:36So that would be methanol, uremia which
3:29:39is to say
3:29:40>> renal failure.
3:29:41>> D stands for DKA, P is propyline glycol,
3:29:44heag glycol, ghostbusters, I is inh or
3:29:49iron, L is lactic acidosis, E is
3:29:52ethylene glycol, it's mud piles, so it's
3:29:54salicycates. So here we have severe
3:29:57congestive heart failure. So very high
3:29:58creatin 8.4 and four also high BUN.
3:30:01There's no ketones in the urine, no
3:30:03glucose in the urine, no drinking
3:30:04alcohol. This is not keto acidosis. And
3:30:06so it's going to be uremia from acute
3:30:08kidney injury due to cigestive heart
3:30:09failure. Why? Cuz the the kidneys are
3:30:11not being profused. So we got some
3:30:13uremia going on here. Betadeema uremia.
3:30:16The sick kidneys cannot excrete the
3:30:18acid. You get uremia. High anap
3:30:20metabolic acidosis. That's what's going
3:30:21on in this question. Okay, here we got a
3:30:2231-year-old woman presented with 9-month
3:30:24history of progressive vision
3:30:26difficulties. Notice some spontaneous
3:30:29nipple discharge. Pretty easy question.
3:30:31This is going to be probably that nipple
3:30:33discharge is probably going to be
3:30:34prolactinoma that inhibits the
3:30:35gonadotropin releasing hormone. So
3:30:36that's our answer. Maybe a way that we
3:30:38can make this question a little harder
3:30:39is we can look at a kind of diagram like
3:30:41this. And here we have to know that this
3:30:43right here is pointed to the
3:30:44hypothalammus. This right here is the
3:30:46phalamus. That's going to be like the
3:30:47midbrain. And here's where you'd have
3:30:49like a pituitary problem, pituitary
3:30:51adenoma. And that could be like some
3:30:53optic cayazm compression of the
3:30:55pituitary adenoma. So here she's got
3:30:56visual testing unable to see objects and
3:30:59in this case we have hyperpolinmia
3:31:01suppressing the G&R manifesting
3:31:02amenorhea and low LH and FSH the
3:31:05pituitary mass is pressing against the
3:31:07optic kayazm explaining her biteal
3:31:08hemopia which looks like that it's the
3:31:10loss of the vision on the outer half
3:31:12okay and our next question we could have
3:31:1529year-old pesticide factory worker
3:31:17maybe it's male maybe it's a female
3:31:19brought emergency department complains
3:31:20of blurry vision excessive sweating and
3:31:22abdominal cramping diaphic bradic cardia
3:31:25and wheezing But pinpoint pupils
3:31:27parasympathetic to activation
3:31:28parasympathetic activation. Colleague
3:31:30mentioned he was exposed to some barrel
3:31:32of organic phosphate. The toxin most
3:31:33likely forms a coalent bond with which
3:31:35amino acid residue. You just have to
3:31:37memorize this one. It's serereine. This
3:31:38is DFP dipopropyl fluoro phosphates.
3:31:41It's an organo phosphate that
3:31:43irreversibly inhibits acetyloline
3:31:44eststerase by binding to the serereine
3:31:46residue at its active site. So
3:31:47acetyloline eststerase is the enzyme
3:31:49that normally breaks down acetylcholine.
3:31:51At its active site, there's a serereine
3:31:53amino acid that does the actual chemical
3:31:55cutting. So you get an organo phosphate
3:31:57that would stick to the serereine and
3:31:59it'll block it forever. So acetylon
3:32:00estesteres can't work. So acetylcholine
3:32:03builds up and you get an over
3:32:04stimulation of the nerves and you get a
3:32:05colonergic crisis. So to answer this one
3:32:07correctly, we have to know the mechanism
3:32:09of organo phosphate poisoning especially
3:32:11at the molecular level. Organo
3:32:13phosphates maybe a child has this as a
3:32:16pesticide. It's a chemical like da
3:32:18isopropyl. Floro phosphate is a potent
3:32:20irreversible inhibitor of acetyloline
3:32:22eststerase and so it binds to the
3:32:24serarine residue at the active site of
3:32:25cetyloline eststerase enzymes. You might
3:32:28think it's histadine and that is part of
3:32:29the catalytic triad but organo
3:32:31phosphates do not bind to histadine. It
3:32:33participates in proton transfer during
3:32:35the catalyis but it is not the
3:32:38nucleophile itself. So a pesticide-like
3:32:40chemical is poisoning a kiddo or
3:32:42poisoning somebody and it irreversibly
3:32:44inhibits acetyloline eststerase and that
3:32:45an enzyme you have to know uses the
3:32:48serereine residue to break down
3:32:49acetylcholine. The toxin covealently
3:32:51binds to the serarine and it stops the
3:32:53enzyme and it causes too much
3:32:54acetylcholine which leads to sweating,
3:32:56the twitching and the weakness. And so
3:32:58seririne is going to be the target
3:32:59there. Next we have a 61-year-old woman.
3:33:01It could also be a man. So I've drawn a
3:33:03man there brought to emergency
3:33:05department by her daughter who says the
3:33:07patient began speaking nonsense. Okay,
3:33:09so this is probably going to be
3:33:11wornizophasia nonsense. You know, they
3:33:13could also say, "All right, we got like
3:33:15an old woman or a man brought to the
3:33:18emergency room by her daughter." And
3:33:19basically what they're trying to get you
3:33:21to understand is the language processing
3:33:23region of the brain like Waricki's area.
3:33:25And the way that Waricki's area and
3:33:27Warick's aphasia looks, it's the left
3:33:29posterior superior temporal gyrus.
3:33:31That's Waricki's area, right? It lies in
3:33:33the domino the dominant hemisphere
3:33:35usually left and it corresponds to the
3:33:37broadman's area 22. But there if you
3:33:39have like an MCA like a middle cerebral
3:33:41artery stroke then you can have fluent
3:33:42aphasia where the speech is fluent and
3:33:44has normal grammar but the rate is
3:33:47nonsensical or paraphasia word
3:33:49substitutions molisms made up and
3:33:52invented words impaired repetition or a
3:33:54lack of insight. So war is just word
3:33:56salad right MCA stroke posterior
3:33:58superior temporal gyrus. So the answer
3:34:00is the inability to repeat simple
3:34:02phrases here you have that's also
3:34:04involved aphasia. So the warning keys
3:34:06area is also involved in repetition. So
3:34:08repetition would definitely be impaired
3:34:10there. Slow effortful would be brocus
3:34:12hemiparesis of the right arm. Brocus
3:34:14aphasia with frontal lobe involvement.
3:34:16Right-sided sensory neglect parietal
3:34:18lesion. Inability to recall three
3:34:20objects would be short-term memory
3:34:21problems. This is bornizasia. All right.
3:34:23Here we have a three-year-old male
3:34:24infant born 36 week gestation. Develops
3:34:26irritability, poor feeding, intermittent
3:34:28tonic clonic movements. Temperature
3:34:3196.6. examination shows tense bulging
3:34:34anterior frontal. His mother did not
3:34:36receive prenatal care and her membranes
3:34:39ruptured 32 hours prior to delivery. Lab
3:34:41stud show luccoytosis and blood cultures
3:34:43pending. Which of the following organism
3:34:44is most likely responsible? So might see
3:34:46some elevated protein in the labs maybe
3:34:48the glucose would be low. Why blood
3:34:51cells could be like elevated? There's a
3:34:53neutrfil predominance. Basically we have
3:34:55to understand neonatal bacteria menitis
3:34:57and the pathogen based on the clinical
3:34:59signs and lab findings all that stuff.
3:35:01Now E.coli Poli is the most common cause
3:35:03of early onset neonat menitis especially
3:35:05in the first 72 hours of life. So some
3:35:07risk factors they might usually say is
3:35:09the lack of prenatal care premature
3:35:11rupture of the membranes prematurity and
3:35:13this is a gram negative lactose
3:35:15fermenting rod and so you can easily
3:35:18identify this on macanki agar. It causes
3:35:20fulminant presentation so poor feeding
3:35:22temperature instability bulging front
3:35:24and seizures and coma. CSF findings in
3:35:27bacterial menitis are going to include
3:35:29high white blood cell count with
3:35:30neutrfil predominance, low glucose and
3:35:33elevated protein. The elevated protein
3:35:34is due to the increased permeability and
3:35:36the inflammation. Low glucose is because
3:35:38the bacteria are just going to be
3:35:39chomping away. They're going to be
3:35:40eating that glucose. High white blood
3:35:41cell with neutrfil predominance makes
3:35:43some sense too. Basically, this ecoli is
3:35:46just causing the sepsis causing menitis
3:35:48in this kiddo and it's just hours or
3:35:50days after the birth which kind of gives
3:35:52it away. You give him ain and
3:35:54genttoyasin as well for empiric
3:35:56firstline treatment. Now the question is
3:35:58how do we distinguish this from other
3:35:59diseases? Well hypothermia seizure
3:36:01bulging fineel means we got a CNS
3:36:04infection and ecoli across the bloodb
3:36:05brain barrier. Lististeria is much less
3:36:08common especially in the absence of
3:36:09maternal food exposure. Strepne
3:36:11pneumonia be rust coloreditis media.
3:36:13Staff epidermititis has shunt associated
3:36:16infections more like with a catheter.
3:36:18Niceria menitis. You'd see that in
3:36:21college dorm rooms. Early onset neonatal
3:36:23menitis is probably going to be E.coli
3:36:25just because like usually they'll give
3:36:27you some sort of a CSF culture. That'll
3:36:29make it really clear. Just they might
3:36:31even tell you it's a gram negative rod
3:36:32if they're being easy. Lactose
3:36:34fermenttor that's unique to E.coli.
3:36:36Nerium menitis that affects older
3:36:38infants, children, and adolescence, not
3:36:40neonates. Sheptoccus pneumonia is more
3:36:42common in toddlers and older children.
3:36:44So this is really just a timeline thing.
3:36:45Listia could be early neonatal menitis
3:36:48but it's a gram positive rod not a gram
3:36:50negative rod and it's usually with like
3:36:52some contaminated food or transplantal
3:36:54transmission something like that for
3:36:55lististeria. So the big kind of takeaway
3:36:58here is that we have a newborn with
3:37:00seizures and a bulging fontel which is
3:37:02neonatal menitis. CSF has a bacterial
3:37:04infection and usually the culture will
3:37:07show like lactus fermenting stuff and
3:37:08that will point to ecoli but yep crosses
3:37:11the blood rim barrier ecoli. Let's do
3:37:13one more question here. All right, here
3:37:14we have a 30-year-old woman, fatigue,
3:37:16dark urine, diffuse itching for the past
3:37:1810 days. Returned from a trip abroad.
3:37:20She was prescribed and document for
3:37:22presumed respiratory infection. Begin to
3:37:25gain new contraceptive pills six weeks
3:37:27ago. On examination, she has mild
3:37:29scleralis and associations on the
3:37:31forearm. Lab studies reveal. Whoa. Hi
3:37:33Billy Rubin. Which of the following is
3:37:35most likely in this patient? Wow, look
3:37:37at that GGT. Normal is like 0 to 30.
3:37:40That's 280. So this is going to be some
3:37:42sort of a drug induced liver injury. The
3:37:44total Billy Rubin should be way lower
3:37:47than that. Usually like 0.1 to 1.2.
3:37:49Direct that's also like super crazy
3:37:52high. Should be like nothing to like 0
3:37:55like to.3. Alkaline phosphatase it's
3:37:58also super high. Should be 40 to 120.
3:38:00About 80 to 40. Super high. ALT about 7
3:38:04to 50 something. 56. That's a little bit
3:38:08high. The GGT is off the charts my guy.
3:38:10All right. So we have some form of drug
3:38:13induced liver injury. The answer is
3:38:15dilated bile caniculi containing bile
3:38:18plugs. So they have choleastatic
3:38:20symptoms, right? Paritis, sclerous, dark
3:38:23urine. Started taking a new pill, you
3:38:25know, that helps to understand that's
3:38:27the medication causing this. But the lab
3:38:29values really just give this away. We
3:38:30have disproportionate like super
3:38:32elevated alkaline phosphotas and GGGT
3:38:35relative to the A and the ALT. And
3:38:38that's going to be suggestive of
3:38:39cholestasis. That's the slowing or like
3:38:42the blockage of the bile flow from the
3:38:44liver to the small intestine. There's
3:38:46also direct hyperbole anemia that
3:38:48supports the impaired flow of the bile.
3:38:50And so the reason why it's these bile
3:38:53plugs because we know it's cholestasis
3:38:55is another way of saying drug induced
3:38:57cholestasis is marked by canalicular
3:38:59dilation of the bile plugs. elevated
3:39:01ALP, GGGT and mild ALT, AS elevation as
3:39:05well and it's associated with oral
3:39:07contraceptive and antibiotics like
3:39:08amoxicylin cluinates and also herbal
3:39:11toxins. Now it's not going to be some
3:39:13form of necrosis that would show super
3:39:15high ALT and A like in the thousands
3:39:17here but there's no evidence of that.
3:39:19It's not we're not seeing any signs of
3:39:21chronic liver disease like hypoalibmia
3:39:23and prolonged PT. Apatosellular
3:39:25ballooning and degeneration would be
3:39:26steepitis from alcoholic or also
3:39:29non-alcoholic fatty liver diseases would
3:39:31be apatoscellular ballooning and that's
3:39:33associated with macrovicular steattosis
3:39:36that's over time not acute iron
3:39:37deposition in apatocytes and the cup for
3:39:39cells that would be hereditary
3:39:41heocromattosis would be cup for cells
3:39:43well iron deposition for sure and so
3:39:45you'd have elevated ferotin transfer in
3:39:47saturation so basically we have a woman
3:39:49who's developed some drug induced
3:39:50colostasis after starting herbal
3:39:52supplements her labs show high ability
3:39:54root high LP GGT classic for choleastic
3:39:58drug induced liver injury. So it shuts
3:40:00down the bile transport system. Oral
3:40:02contraceptives can do that with
3:40:03especially when they combine with
3:40:04antibiotics. So colatic drug induced
3:40:06liver injury is what's going on with
3:40:07this patient right here. All right, if
3:40:09you found this helpful, then like and
3:40:10subscribe. We'll see you guys in the
3:40:11next one. Welcome back to MBME29. Today
3:40:13we're continuing with question 11. These
3:40:15are all original questions. Like and
3:40:17subscribe. So here a 3-year-old girl is
3:40:19brought to the clinic by her parents due
3:40:20to concerns about developmental
3:40:22regression. She had a normal development
3:40:24until about 18 months of age when she
3:40:25began losing the ability to speak and
3:40:27stopped using utensils or toys with her
3:40:30hands. Over the past several months, she
3:40:31has developed repetitive clapping
3:40:33motions and frequently rings her hands
3:40:35together. Parents noticed her head
3:40:37appears smaller compared to other
3:40:38children her age. Physical exam, she has
3:40:40a blank facial expression and she
3:40:42periodically hyperventilates. Which of
3:40:43the following is the most likely
3:40:45underlying mechanism of this condition?
3:40:46Okay, those are our answer choices. So,
3:40:48this condition is RED syndrome. It's a
3:40:50mutation in the Mech P2 gene, which is
3:40:53an Xlink dominant mutation that's
3:40:55usually lethal in males. So, Mech P2,
3:40:58it's a critical transcription repressor
3:41:00that keeps the genes in check in the
3:41:02neurons. When it fails, the neurons
3:41:04can't mature normally. And usually, this
3:41:05is going to be present in girls between
3:41:07about 6 to 18 months who are developing
3:41:09normally and then they start to regress.
3:41:11So, you should look for the loss of
3:41:12language, hand function, microphille,
3:41:15and also the hand ringing movements.
3:41:16There also going to be some strange
3:41:18breathing patterns. And here's a more
3:41:19in-depth breakdown. Ted repeat would be
3:41:21fragile X. Deletion of 15 Q is angel
3:41:24man's. Imprinting would be like prader
3:41:25willies. There you see obesity hypotonia
3:41:28as well. And tumor suppressor loss is
3:41:30leaf from any not related to
3:41:31neurodedevelopmental regression. So the
3:41:33big clue here is the regression. The
3:41:35mutation on mechp in the ext chromosome
3:41:37is the answer. Okay. For our next
3:41:38question, we have a 76y old woman. She's
3:41:41brought to the emergency department for
3:41:42sudden onset severe upper abdominal
3:41:44discomfort and repeated dry heaving
3:41:46after large meal. She's got intermittent
3:41:48bloating, difficulty swallowing,
3:41:50especially after lying down. She denies
3:41:52recent alcohol use or prior history of
3:41:54ulcers. Vitals show hypotension and
3:41:56teacardia. Physical exam has epigastric
3:41:58tenderness and mild abdominal
3:42:00distension. A nasogastric tube cannot be
3:42:02advanced to the stomach. Chest X-ray
3:42:04shows large retrocardiac air fluid
3:42:07level. What's the most likely
3:42:08predisposing factor for this condition?
3:42:09And the answer is a parasophageal hernia
3:42:12allowing gastric displacement. So when
3:42:14the stomach rotates on itself, it causes
3:42:16a rare and life-threatening emergency
3:42:18called gastric vulvus. You should think
3:42:20about it like a twisted balloon. The air
3:42:21and the contents just can't escape. And
3:42:23so you get what's called Bortchard's
3:42:24triad. You have epigastric pain, dry
3:42:27heaving, and the inability to pass an NG
3:42:29tube. So there's that twisting and
3:42:30inability to pass. Now what lets this
3:42:32happen? Most often it's a parasophageal
3:42:35hernia. It's a type of hernia where part
3:42:37of the stomach will slip through the
3:42:38diaphragm beside the esophagus. That
3:42:40kind of looks like this. So we have our
3:42:41normal diaphragm, normal stomach, weak
3:42:43diaphragm, hyal hernia, and here is our
3:42:46parasophageal hernia. There's our
3:42:48parasophageal hyal hernia. So part of
3:42:51the stomach is literally slipping
3:42:52through the diaphragm beside the
3:42:53esophagus. And the clues that tell us
3:42:55it's an underlying chronic hernia
3:42:56condition would be that history of
3:42:58postmeal bloating and dysphasia. So
3:43:00that's why our answer is D. Trap
3:43:02answers, gallstone migration. There
3:43:04you'd have intermitted right upper
3:43:06quadrant pain and pancreatitis. Dadinal
3:43:07ulcer with fibrosis that would present
3:43:09with chronic outlet obstruction. So and
3:43:11that gastric outlet obstruction is where
3:43:13you have persistent vomiting, early
3:43:14satity because there's a mechanical
3:43:16obstruction and this is seen where
3:43:18causes of this are peptic ulcer disease,
3:43:20gastric cancer and infiltrative
3:43:21diseases. You'd have non-billis
3:43:23vomiting. It's associated with peptic
3:43:24ulcer disease, gastric cancer, chronic
3:43:26use, pancreatic carcinoma. It also has
3:43:28some infectious causes like TB. And all
3:43:30that's happening here is there's chronic
3:43:31inflammation or a tumor that causes a
3:43:34progressive narrowing of this pyloric
3:43:36canal you can see here. And so gastric
3:43:37emptying becomes impaired and you get
3:43:39retention of the gastric contents that
3:43:41can cause vomiting. So you get a loss of
3:43:42hydrronium and also chloride and so you
3:43:44get metabolic alkyossis and then the
3:43:46kidney will compensate and you get
3:43:47paradoxal acidia. That's where you try
3:43:49to conserve sodium at the expense of
3:43:50hydrogen. So all this to say that's
3:43:52dadinal ulcer with fibrosis would be
3:43:54that condition. Mar rotation with the
3:43:56lad bands is common in infants that
3:43:57would have bilis vomiting and incest
3:43:59deception has the current jelly stools
3:44:01and colicki abdominal pain. Okay, next
3:44:04we'll call the last one a bonus and
3:44:05we'll call this one 12. Here we have a
3:44:0672year-old male presents to the
3:44:08emergency department because he fainted
3:44:09while getting up from the toilet. He's
3:44:11got mild diarrhea for the past 2 days
3:44:12not been eating and drinking. Well, he
3:44:14takes Linipril and chloraladone for
3:44:16hypertension. Supine blood pressure is
3:44:18132. After standing 2 minutes, his blood
3:44:20pressure drops to 98. What describes the
3:44:21immediate changes that occur when you're
3:44:23standing up? So I've drawn this person
3:44:24laying down and then standing up.
3:44:26There's less blood return. So it's
3:44:27hypoallmic state causes less venus
3:44:30return and there's going to be less of
3:44:31that firing because there's less blood
3:44:33to fire those receptors. And then that
3:44:35lack of profusion of oxygen or increase
3:44:37of CO2 is going to cause cerebral
3:44:39profusion to decrease. So this is
3:44:41hemodynamic orthostatic hypotension.
3:44:43This is seen in hypoalmia or shock
3:44:45states. You have decreased blood
3:44:46pressure and cerebral hypoprofusion. So
3:44:49when you stand up suddenly then gravity
3:44:51pulls the blood into the legs and that
3:44:53causes decrease venus return and so you
3:44:55have a decreased preload that decreases
3:44:57the stroke volume as you decrease the
3:44:58cardiac output and that decreases the
3:44:59arterial pressure that's sensed by the
3:45:01barrel receptors in the crowded sinus
3:45:02and also the aortic arch and the
3:45:04decreased barreceptor firing normally
3:45:06increases you know the sympathetic tone
3:45:08but here you have decreased
3:45:09parasympathetic firing and so in
3:45:11autonomic failure this compensation is
3:45:12blunted and so you have cerebral
3:45:14hypoprofusion and syncopy usually we we
3:45:16describe this as a 20 mm mercury a
3:45:18systolic blood pressure or a greater
3:45:20than 10 change in diastolic pressure
3:45:22drop when you your stamp and the
3:45:24culprits that you'll often see with this
3:45:25are like your diuretics alpha blockers
3:45:27TCA Parkinson meds diabetes that kind of
3:45:29thing and that decreased cerebral
3:45:31profusion comes directly from that
3:45:33decreased mean arterial pressure when
3:45:35the MAP fails then the cerebral blood
3:45:36flow will drop and so you might have
3:45:38brain hypoxia so you get dizziness
3:45:40blurred vision syncopy weakness and the
3:45:42brain is just super sensitive to the
3:45:43drops in profusion for instance even a
3:45:4510 to 15 mm mercury drop in map can
3:45:49reduce the cerebral blood flow by about
3:45:5120 to 30%. And that's enough to cause
3:45:53syncopy in vulnerable patients. That's
3:45:55why they're typically going to be
3:45:56elderly like the 72-year-old male. For
3:45:58this next question, we have a 39year-old
3:46:01male undergoing evaluation for chronic
3:46:03mucinous candidasis. As part of the
3:46:05immune workup, he receives intrammal
3:46:07injection of heat killed candida. After
3:46:0948 hours, a test site shows 15 mm area
3:46:12of induration with surrounding athemma.
3:46:14Which of the following is most likely
3:46:16the predominant immune cell type at the
3:46:18ejection site? The answer is
3:46:20macrofasages. So here we have a positive
3:46:22candidate skin test. Very similar to a
3:46:23PPD test. They're both type four
3:46:25hyperensitive reactions. The delay is
3:46:27driven by TH1 cell activation. Then that
3:46:29attracts your macroofages. Plasma would
3:46:31be type two and three. Phils is type
3:46:33one. Neutrfils are acute, not delayed.
3:46:35Natural killers would target the virally
3:46:37infected ones but not the primary
3:46:38mediators here. So basically if you
3:46:40inject Canada antigen into somebody's
3:46:42skin and you check back a couple of days
3:46:43later then you're no longer testing just
3:46:45for a fungus you're actually testing for
3:46:46the tea cells because that enderated
3:46:48hump at 48 hours is not pus that is the
3:46:51result of a type 4 hypersensitivity
3:46:53reaction and that is driven by TH1 cells
3:46:55and macrofasages. So macrofasages are
3:46:57the main aectors they're recruited by
3:46:59interferon gamma from the activated tea
3:47:01cells and they release the enzymes and
3:47:03the cytoines that cause the tissue
3:47:05swelling and the firmness. So it's all
3:47:06about the cell mediated immunity. Okay,
3:47:09next. This is an ethics lesson. We would
3:47:10all do well to listen and validate
3:47:12before speaking. So, always think about
3:47:14patient autonomy. Think about listening
3:47:15to what their concern is. Ask them more
3:47:16questions about it. So, we'll make up a
3:47:18question. This guy's got diabetes type
3:47:19one. He says, I'm not sure. All you've
3:47:21done is stick me once. And instead of
3:47:22saying, just, you know, trust me, I'm a
3:47:23doctor. Or, do you want
3:47:24anti-depressants? Or something crazy
3:47:26like that. You just say, could you tell
3:47:27me about some of your concerns? Or,
3:47:29could you tell me what you think this
3:47:30is? Try to open up the conversation.
3:47:32Question marks are always a good thing.
3:47:33Patient anxiety often mass deep fears.
3:47:35So, you have to have empathetic
3:47:37listening. Don't jump to facts without
3:47:38emotional validation or else you can
3:47:40shut down the conversation. For this
3:47:42question, let me ask you, are these your
3:47:44rods? No, these are our rods.
3:47:48You guessed it. The next whose answer is
3:47:50a cumious leukemia. Well, you might come
3:47:52up with central palar thrombocyopenia.
3:47:54And that's what we've done here. A
3:47:5535-year-old man has fatigue, easy
3:47:56bruising, nose bleeds. He's got some
3:47:58pitikia over his lower limbs and mild
3:48:00palar. Look at those platelets. And we
3:48:02have numerous large blasts with open
3:48:04chromatin and a few containing
3:48:06needle-shaped cytoplasmic inclusions.
3:48:09Our rods in your question you might also
3:48:10have mentioned 15 to 17 transllocation
3:48:12increased risk of DICE. You talk about
3:48:14down syndrome where you have an
3:48:15increased risk of AML or mutations in
3:48:17the myo progenitor cells. Could have
3:48:18mentioned the cytoineas low HB white
3:48:20blood cells that could be high the CD-13
3:48:23positive on the flowcytometry. basically
3:48:24could have gone a lot of ways but acute
3:48:26myoid leukemia is a clonal malignancy of
3:48:30myoid progenitor cells in where the bone
3:48:33marrow now this is characterized by
3:48:34super rapid proliferation of the
3:48:37immature myoid cells those are called
3:48:39myoblasts you get bone marrow failure
3:48:41because of the crowding out of the
3:48:42normal hematopois and this can happen at
3:48:44any age but it's most commonly in adults
3:48:46that are greater than 65 years old but
3:48:48any age and what causes this is a
3:48:50genetic mutation at 1517 that's the APL
3:48:53subtype that involves the PML
3:48:56R alpha fusion gene and you treat it
3:48:59with all transinoic acid. There are some
3:49:01risk factors to look out for on test
3:49:02day. One would be chemo or radiation.
3:49:04You can have therapy related AML, myoid
3:49:07displastic syndrome that can progress to
3:49:09AML and then of course down syndrome
3:49:10especially if it's before the age of
3:49:12five can predispose you as well. And
3:49:14some lesser known ones are the benzene
3:49:16exposure, smoking, industrial solvents,
3:49:18fuconia anemia, bloom syndrome and other
3:49:20DNA repair mechanisms. But the pathophys
3:49:23for AML is very important. You have
3:49:25myoid stem cells that acquire mutations
3:49:27and then they start to just bang out all
3:49:28these immature precursors and then those
3:49:30fail to differentiate and so you get a
3:49:32bunch of blasts in the marrow and that
3:49:34crowds out the normal cells. You get
3:49:35anemia, thrombocyopenia, neutropenia.
3:49:38You can't make stuff because the bone
3:49:39marrow ain't working anymore. It's too
3:49:40crowded. And so the blast then start to
3:49:42spill into the blood. So you have an
3:49:43elevated white blood cell count and
3:49:45possibly DIC at least in acute
3:49:47promolytic leukemia. So usually you'll
3:49:50see greater than 20% myoblasts in the
3:49:53bone marrow that's diagnostic for it and
3:49:54then our rods not your rods are the red
3:49:56needleike inclusions in the cytoplasm of
3:49:58the blasts and also importantly you see
3:50:00MPO positivity on these stains but
3:50:03that's probably too easy they won't tell
3:50:04you that. Cool. That's question 15 in a
3:50:06nutshell. Now for this next one we have
3:50:07a 65year-old woman. She's brought to the
3:50:09E. She's got fever, chills, productive
3:50:11cough for the last 4 days. Her speedum
3:50:13is yellow green. She has puritic chest
3:50:15pain and mild shortness of breath.
3:50:17temperature is 39 to 102.4 degrees
3:50:19Fahrenheit. Which of the following
3:50:20findings is most likely present? The
3:50:22answer is increased tactile fitus over
3:50:24the left lower lobe. This is interesting
3:50:26because when pneumonia hits the sound
3:50:29actually travels better because the lung
3:50:31tissue is going to be consolidated. So
3:50:33in lowar pneumonia you're not going to
3:50:35block the sound you're going to amplify
3:50:36it. So increased tactile fitus and
3:50:38bronchial breath sounds. You can also
3:50:40have egophony you know the e to a change
3:50:43sound. If you hear dullness to
3:50:44percussion and harsh tubular breathing
3:50:46sounds in the periphery, then that's a
3:50:48huge big red flag for pneumonia. So here
3:50:49are some of the buzzwords we talked
3:50:51about. Here are the associations. So
3:50:53plural eusion would have decreased and
3:50:55dullness and decreased breath sounds.
3:50:57Numo would have decreased femitis but
3:50:59hyper resonance. That's super important
3:51:00for your tension for pneumothorax air.
3:51:02And then lowardonia has all three sounds
3:51:05increased. The pathophys is that there's
3:51:07an infection of the avular excidate that
3:51:09replaces the air with fluid and pus that
3:51:11increases the conduction because it's
3:51:12consolidated and it vibrations you can
3:51:13hear and the percussion is dull. It's
3:51:15not hyper resonant because it's filled
3:51:16with fluid content. So yeah, the
3:51:18vibrations don't lie. Importantly, the
3:51:19signs of pneumonia are going to be like
3:51:20the cough, you know, you get like the
3:51:22fever or like some yellow sputum, stuff
3:51:24like that. Also, maybe they'll have some
3:51:25pain on the right side of their chest
3:51:26whenever they breathe in and then
3:51:28they'll have like some sort of a fever.
3:51:29So you look at that, you say, "Oh my
3:51:30gosh, that's pneumonia." Pneumonia is
3:51:32going to have consolidation of that pus
3:51:33in the avular excuteate. that air is
3:51:35going to be gone, so it's going to be
3:51:36consolidated. So, all these sounds are
3:51:37going to be increasing on the affected
3:51:39side. So, you have increased tactile
3:51:40framitis. Does that make sense? If that
3:51:41made sense, then be sure to like and
3:51:43subscribe. Next, we're going to talk
3:51:44about the kidney. So, there's a
3:51:4568-year-old man. He's admitted to the
3:51:47ICU following septic shock secondary to
3:51:49peritonitis. He was hypotensive. Now, on
3:51:51day two, his urine output decreases.
3:51:53Which of the following nephron segments
3:51:54is most likely to show irreversible
3:51:55injury? And that's the proximal
3:51:57convoluted tubial. Now, I want to do
3:51:58something fun on this question. First,
3:51:59I'm going to explain, but then I want to
3:52:01talk about how this applies to the rest
3:52:02of the human body. So we have eskeemic
3:52:04acute tubular necrosis after septic
3:52:06shock. The proximal tubule is the most
3:52:08susceptible to that. It's the first site
3:52:09injured during hyper profusion. And you
3:52:11can look at the iron sodium to confirm
3:52:13intrinsic renal failure. The collecting
3:52:15duct is also affected but less
3:52:17metabolically active than the proximal.
3:52:19It's less susceptible. Glaryi, DCT,
3:52:22these are all less metabolically active
3:52:24and so not as susceptible. So the part
3:52:25that works the hardest is the part that
3:52:27breaks under pressure as the proximal.
3:52:28Now with that being said, what are some
3:52:30other areas of eskeemic necrosis and
3:52:32lesions that you can have? So we
3:52:34mentioned the proximal tubule, but a
3:52:35huge one is obviously going to be the
3:52:37brain. That's the most sensitive tissue
3:52:38to hypoxia and hypopusion. There you
3:52:40have irreversible neuronal injury that
3:52:42can happen even just 3 to 5 minutes out.
3:52:44And so the especially vulnerable areas
3:52:46are like the hippocampus, the perkingi
3:52:48cells of the cerebellum, neoortex
3:52:50layers, that stuff. Also the heart. Ever
3:52:52heard of a heart attack? It's kind of a
3:52:54thing, huh? So the subendocardium of the
3:52:56left ventricle is the most at risk area.
3:52:58is the furthest from the coronary blood
3:53:00supply and experiences the highest
3:53:01pressure during cy. Okay. Now, how about
3:53:03the intestines? There's some watershed
3:53:05areas that are vulnerable. One is the
3:53:06splenic flexure region. That's between
3:53:08the SMA and the retoigmoidal junction.
3:53:10That's between the IMA and the
3:53:11hypogastric. It's poorly profused. You
3:53:12get hypotension and eskeemic colitis in
3:53:14the elderly and posttop patients. Now,
3:53:16the big one is the retina. So, those
3:53:17guys have high oxygen demand and there's
3:53:19no collateral flow. And so, if you have
3:53:20central retinal artery occlusions, then
3:53:22you're going to have painless vision
3:53:24loss. No oxygen, central retinal
3:53:26arteries accluded. Cool. Beans. Okay,
3:53:28our next topic is going to be the sun.
3:53:29Mr. Sun came up and you smiled at me.
3:53:32So, what is this crazy weird thing that
3:53:34I've drawn? That is a cholesterol
3:53:36precursor that's found in the skin. It
3:53:38plays two roles and then two, it's
3:53:39precursor to vitamin D3 and it has to be
3:53:42exposed to UVB sunlight. So, it's formed
3:53:45in the cholesterol synthesis pathway
3:53:47just before the cholesterol itself and
3:53:48it plays a big role in vitamin D
3:53:49production. So in the epidermis the UVB
3:53:52hits it it converts it to pre vitamin D3
3:53:54and then vitamin D3 coliferol travels to
3:53:58the liver and I'll write this down and
3:53:59we get the activated 125 dihydroxy
3:54:02vitamin D which is calcitrial and that's
3:54:04our active vitamin D. So skin liver
3:54:07kidney and if you have kidney failure
3:54:08then you have low active vitamin D right
3:54:11liver disease then sunscreen will cause
3:54:13decreased vitamin D synthesis and I
3:54:14think we're ready for a question. So, we
3:54:16have a 16-year-old male moved to
3:54:18California, spending most days
3:54:19skateboarding on the beach. He's got the
3:54:21juice. Okay. Anyways, past 3 months,
3:54:23he's grown 6 centimeters in height,
3:54:25increased appetite and energy, alkaline
3:54:26phosphotase levels are within normal
3:54:28range for his age. Which of the
3:54:30following is most directly responsible
3:54:31for his increased intestinal calcium
3:54:33absorption? The answer is the
3:54:35transcriptional effects of UV activated
3:54:36dermal chiciferol. So that's the
3:54:39conversion of that 7 D hydro cholesterol
3:54:42and the vitamin D3 in the skin that
3:54:44causes our active vitamin D and that
3:54:46helps us get our calcium and phosphate
3:54:47absorption. So here's the pathway
3:54:49radiation 7D dehydro cholesterol to
3:54:52choliciferol vitamin D3 liver makes it
3:54:54into 25 kidney through one alpha
3:54:57hydroxilase converts it to 125 and we
3:54:59get the transcription of our channels
3:55:00and that binds calcium inside of the
3:55:02entites allows more calcium to be
3:55:03absorbed. So, there's a pathway from the
3:55:06sun to calcium in your body pointing to
3:55:09me or thank you, son. All right, this
3:55:10one's going to be super duper buzzy. We
3:55:12have a 70-year-old man presenting to
3:55:14primary care physician for evaluation of
3:55:15gate instability. His wife notices
3:55:17progressive worsening handwriting,
3:55:18difficulty rising from chairs and
3:55:20hallucinations. They could also say
3:55:21cogill rigidity. This is definitely
3:55:23Parkinson. So, what is the protein
3:55:25composition? The answer is alphasuclean.
3:55:27This is a memorization question. So,
3:55:29what is alphasuclean? It is a neuronal
3:55:31protein that's involved in the synaptic
3:55:33vessels regulation and neurotransmitter
3:55:34release especially dopamine and it's
3:55:36found in the presaptic terminals and
3:55:38when it's misfolded alphasuclean becomes
3:55:40insoluble and it can aggregate and
3:55:41that'll cause Louis bodies right and so
3:55:43this is involved in Parkinson disease
3:55:45where the Louis bodies in the substantia
3:55:47[ __ ] pars compacta and I'll show you
3:55:49that there we go there's a healthy
3:55:51there's a substanti right you lose that
3:55:53dopamine and another one is louisibody
3:55:54dementia and that's in the cortical
3:55:55neurons so that would be our louisibody
3:55:57dementia so if you look at alphasuclean
3:55:59you think oh man one's Parkinson's one's
3:56:00Louis body dementia. Yeah, but it's
3:56:02multiple things, right? There's also
3:56:03multi-system atrophy. There are a lot of
3:56:06alpha nucleanopathies, but the pathophys
3:56:08is basically you have alpha nuclean as
3:56:10misfolds. It can aggregate into like
3:56:11Louis bodies and then it impairs
3:56:13neuronal function and survival. So look
3:56:15for Louis bodies and also Parkinson
3:56:16stuff, but the answer is definitely
3:56:17alphasuclean. Think of a for abnormal
3:56:19synapse. Alpha. Okay, there is our
3:56:21explanation. I'll move myself out of the
3:56:22way so you can see Louis bodies
3:56:24alphauclean. Beta amalloid is
3:56:25Alzheimer's. Tao is Alzheimer's frontto
3:56:28temporal. So different changes in the
3:56:29personality. Louis would have
3:56:30helinations Louis bodies pron protein
3:56:33associated with spondo form changes
3:56:35TDP43 found an ALS. Okay. Now for this
3:56:38one we have a clinical trial. We're
3:56:40evaluating the anti-hypertensive drug
3:56:42utility. 40 patients in stage 1
3:56:44hypertension are randomly assigned to
3:56:45receive either the new drug or a
3:56:46different one. 8 weeks later we get the
3:56:48means and we want to determine if
3:56:49there's a difference in the means. What
3:56:50are you going to do? Student t test.
3:56:52It's how you compare the means of two
3:56:54things. Unpaired student t. Kai squared
3:56:56categorical data male female dead alive.
3:56:58Paired is when the same subjects are
3:57:00measured twice before and after. ANOVA
3:57:02is for three or more and linear
3:57:04regression predicts the dependent
3:57:05variable based on a couple independent
3:57:07variables. So a student t test would
3:57:09calculate the p value based on the
3:57:10difference of the means. This guy over
3:57:12here you look at the difference between
3:57:13them, the standard deviations, the
3:57:14sample sizes, all that stuff. And if the
3:57:15p value is less than 005, you reject the
3:57:18null hypothesis and it means that this
3:57:20new method probably had an effect.
3:57:21Student t is two group means. Paired t
3:57:24test is before and after. ANOVA is three
3:57:26or more. And kai square is for
3:57:28proportions. All right, guys. Hopefully
3:57:29that was helpful. We just finished 10
3:57:30more questions. Please be sure to like
3:57:32and subscribe if you found this
3:57:34interesting. Make sure you guys get your
3:57:35physical exercise in today. Let's not
3:57:36waste any time. Let's dive right in.
3:57:3817-year-old girl is brought to the
3:57:40emergency department with high fever,
3:57:41phototohobia, and particular rash. She
3:57:44has a history of two prior
3:57:45hospitalizations for neria. That should
3:57:47immediately make us think of deficiency
3:57:49in the MAC complex formation. And indeed
3:57:51our correct answer is the deficiency of
3:57:52the terminal complement components. All
3:57:54right. So this is a very easy question.
3:57:55I want to break it down simply. The
3:57:56terminal complement pathway which is C5
3:57:59to C9 forms what's called the membrane
3:58:02attack complex and the MAC creates pores
3:58:05in the membrane of gram negative
3:58:07bacteria. And so a deficiency in these
3:58:09compliments especially C6 7 8 or 9
3:58:12causes an inefficient MAC formation and
3:58:15that allows for these gram negative
3:58:17bacterium for instance neria infections.
3:58:19think niceria menitis or nera ganorrhea
3:58:22to be able to form and other infections
3:58:23are not as common because optinization
3:58:26which occurs via the C3B pathway is
3:58:29usually intact. So this is a really
3:58:31basic immunology question. It's about
3:58:33the compliment system. You should look
3:58:34for a deficiency in C5 to C9. If you
3:58:37have recurrent niceria bacteria all
3:58:39right there's our explanation. Let's
3:58:41look at the trap answers and why they're
3:58:42wrong. C1 eststerase inhibitor. So that
3:58:45deficiency causes what's known as
3:58:47hereditary angioadema not infections.
3:58:50And the pathophysiz there is you have
3:58:51increased brady kinanine because of the
3:58:53unchecked calocrints which are the
3:58:55family of the serereirine proteases that
3:58:57are involved in all sorts of things like
3:58:59blood pressure regulation inflammation
3:59:00tissue remodeling all that stuff. So
3:59:02with C1 estrays inhibitors you should
3:59:04think of the condition known as brady
3:59:05kindinam mediated angioadeema because
3:59:07that's life-threatening swelling of the
3:59:08deep layers of the skin or the mucosal
3:59:10tissues. And this is actually different
3:59:11than histamine mediated angiodma which
3:59:13often includes like hives and itching.
3:59:16This type is non-pitting and it's not
3:59:18accomplished by udicaria. I don't want
3:59:20to get too deep into the weeds here but
3:59:21this pathophys involves the contact
3:59:23system which is a plasma protein cascade
3:59:26that's responsible for inflammation and
3:59:28that causes an excessive accumulation of
3:59:30bradyin and bradkin is a vasoddilator
3:59:32that increases the vascular permeability
3:59:34and leads to fluid leaking from the
3:59:35blood vessels into the surrounding
3:59:37tissues. And so C1 estra inhibitor
3:59:40that's a key enzyme that normally
3:59:41inhibits that contact system. And so if
3:59:43it's deficient or dysfunctional
3:59:46hereditary angioadeema or something else
3:59:48that will cause uncontrolled activation
3:59:50of the pathway and then you have
3:59:51unchecked calocrine activity and plasma
3:59:53calocrine will not be properly inhibited
3:59:55and that's what causes the excessive
3:59:56bradkin. Also be on the lookout for
3:59:58angotensin converting enzyme ACE. That's
4:00:01a metabolizer of bradyinine and so if
4:00:03you give somebody an ACE inhibitor that
4:00:05will block that process and it leads to
4:00:06bradyinine buildup and that can be a
4:00:08life-threatening angiodma. All right, so
4:00:10we dove way into that option. IgA
4:00:12deficiency would have recurrent mucosal
4:00:15infections does not explain the niceria.
4:00:17So think mucus for that one. Factor H
4:00:19deficiency atypical hemolytic uremic
4:00:22syndrome that regulates the alternative
4:00:24pathway which is not selected for
4:00:25niceria and beta 2 microlobuline
4:00:28deficiency would be an absent MHC class
4:00:301 and so that's associated with CD8
4:00:32positive T- cell which remember MHC1 *
4:00:358= 8 whereas MHC class 2 * 4 would equal
4:00:388 so this is noniceria but individuals
4:00:41who do not have the C5 to C9 complexes
4:00:44are at about 7,000fold increased risk of
4:00:47getting infection ctions. Okay, so there
4:00:49are the buzzwords and the associations.
4:00:51One thing I want to note is that factor
4:00:53B and H should make you think of the
4:00:55alternative complent pathway. Factor B
4:00:57makes C3 convertase and factor H
4:01:00regulates that convertase. And so if
4:01:01those are deficient, you have
4:01:03uncontrolled compliment and that's
4:01:04atypical HUS, not Niceria infections.
4:01:07And then the other thing to know is that
4:01:08these beta 2 micro microglobulins are
4:01:11components of the MHC class one
4:01:13molecules and so deficiency impairs CD8
4:01:15positive T- cell activation. The long
4:01:17story made short here that recurrent
4:01:19nicer infection should make you think of
4:01:21MAC C5 to C9. All right, for our next
4:01:24topic, I like this title, don't drink
4:01:26and dose. So, let's dive in. We have a
4:01:2821-year-old college student presenting
4:01:30with follow-up after beginning treatment
4:01:32for chlamial urethritis with oral
4:01:34doxycycline. He reports that despite
4:01:35strict adherence to his dosing schedule,
4:01:37his symptoms have not improved over the
4:01:40last 5 days. Further questioning reveals
4:01:42that he takes his medication every
4:01:43morning with a bunch of milk products.
4:01:46Which of the following is likely the
4:01:47explanation for the reduced efficacy?
4:01:49The answer is complexation with dietary
4:01:51calcium. So we have a patient coming in
4:01:53with acne treatment using tetracycline
4:01:55but it stops working when he has milk
4:01:57essentially. So to answer this question
4:01:59we have to know what tetracyc are like
4:02:00tetracyc doxycycline monocyc. These are
4:02:04bacterioatic antibiotics that inhibit
4:02:07protein synthesis by binding to the 30S
4:02:10ribosomal subunit and they are highly
4:02:12sensitive to a process known as
4:02:13keelation and that's when the b or poly
4:02:15dentate lian bonds with a metal or a
4:02:18metal ion and it forms a stable ring
4:02:20structure known as a chilate ring.
4:02:22Usually keation is a treatment for
4:02:23people who have too much metal in their
4:02:24body. It removes the metals and other
4:02:26elements right because the chilator is
4:02:27attached to the metals in your body and
4:02:28your body can then get rid of those
4:02:30metals through the urine and the feces.
4:02:31as we were saying are super susceptible
4:02:34and sensitive to keelation. So diovalent
4:02:36cations ions like calcium, iron,
4:02:38magnesium they bind to tetracycans in
4:02:41the GI tract and this forms insoluble
4:02:43complexes that cannot be absorbed and so
4:02:44you have decreased bioavailability. And
4:02:46the thing that you should know then okay
4:02:48why are we talking about all of these
4:02:49awesome dialent cations ions? Well milk
4:02:52contains calcium check the charge
4:02:55dialent so that chelates tetracyc and it
4:02:58prevents its reabsorption. So this is an
4:02:59antimicrobial tetraycling question. In
4:03:01the pharmacology realm, you do not take
4:03:03milk, that is to say calcium, a dvillan
4:03:06ion, or ant acids. Why? Because that's
4:03:08also going to have magnesium, which is
4:03:10also dvalent or any iron containing
4:03:12preparations because dvillain cations
4:03:14ions can inhibit the drugs absorption in
4:03:16the gut. A enhanced metabolism by hpatic
4:03:20enzymes. Nope, doesn't use the sip
4:03:21heavily. C competition with other ones.
4:03:24That'd be like warin displacement. It
4:03:25has nothing to do with the protein
4:03:26binding competition with warrin.
4:03:28Degradation in acidic environment that's
4:03:30acid labile drugs and altered renal
4:03:33excretion. Toxycycline is mostly fe
4:03:35excreted. So yeah, drinking milk can
4:03:37actually make your antibiotics stop
4:03:39working. Also be on the lookout for
4:03:40things like iron supplements. In another
4:03:42world, they could have asked this
4:03:43question differently. Calcium
4:03:44supplements, ant acids, magnesium is
4:03:47dvalent, even you know zinc. Just be
4:03:50aware of the effect that chilators can
4:03:51have on tetracyc and anything that binds
4:03:53the 30s subunit. In our next question,
4:03:55we have a 56-year-old woman presenting
4:03:57with worsening fatigue and decreased
4:03:59urine output over the past 2 weeks. She
4:04:01also notes spotting of blood after
4:04:03intercourse and pelvic discomfort. Her
4:04:04past medical history includes chronic
4:04:06tobacco use and no recurrent gynecologic
4:04:09exams. Lab results show elevated serum
4:04:12creatin and bun. Pelvic ultrasound shows
4:04:14bilateral hydrotorittors and
4:04:16hydronphosis. No stones or masses are
4:04:19noted in the kidneys and irriters.
4:04:20Pelvic examination reveals ulcerated
4:04:22cervical leion. Which of the following
4:04:24is most likely the cause of her renal
4:04:25findings? Before diving into the answer,
4:04:27I want to explain the lay of the land.
4:04:29Cervical cancer when it's locally
4:04:30invasive can spread laterally and
4:04:32involve the parimetrium and the urittors
4:04:34especially near the ureicular junction.
4:04:37And that is what's causing in this
4:04:39patient the bilateral ureiteral
4:04:41obstruction. And that leads to the
4:04:42hydrotorittors, hydronosis and
4:04:45post-renalmia. And what is post-renal
4:04:48ismia? That's when you have an increased
4:04:50bun to creatin ratio. So this is a
4:04:53reproductive female gynecological tumor
4:04:55question. You just have to know the only
4:04:56common cancer that causes bilateral ural
4:04:59obstruction due to a local invasion.
4:05:01It's invasive squamous cell carcinoma of
4:05:04the cervix. It can invade locally and
4:05:05invade the urittors and that can then
4:05:07cause the renal failure. And the most
4:05:09common site of the distant metastasis in
4:05:11cervical cancer is actually going to be
4:05:14the lungs. Now I just wanted to clarify
4:05:16post-renalmia and how it relates to BU
4:05:18and creatinin. So amia is just a fancy
4:05:21word of saying hey we've got elevated
4:05:24waste products primarily BU and there
4:05:26are three categories that you should
4:05:27know. There's prenal, intrinsic and
4:05:30post-renal.
4:05:32Intrinsic is where you actually have
4:05:33damage to the kidney itself. There you
4:05:35should think of acute tubular necrosis.
4:05:37Postrenal is an obstruction of urinary
4:05:38outflow stones in this case cervical
4:05:41cancer. And so in post-renalmia, what
4:05:44happens is you have an obstruction. The
4:05:45urine backs up to the bone in space. If
4:05:48you have increased hydrostatic pressure
4:05:49that reduces while GFR depends on the
4:05:52stling forces across the glomemeular
4:05:55capillary membrane. There's a blockage
4:05:56downstream, right? Like cervical cancer
4:05:58compressing against the urittors. The
4:06:00urine then backs up to the renal pelvis
4:06:02and then in the collecting ducts and the
4:06:04tubules and ultimately all the way into
4:06:06Bowman's space. Bowman's like, "Yo,
4:06:09because of this blockage, you're in my
4:06:10space." Now, why does this lower GFR?
4:06:12Well, that increased pressure in the
4:06:14Bowman space pushes against the
4:06:15filtration of the plasma from the
4:06:16capillary. And so, even if glomemeular
4:06:18pressures are high, the net filtration
4:06:20pressure will drop as the GFR decreases.
4:06:22Maybe a good analogy for this is imagine
4:06:24you're trying to pour water through a
4:06:26hose into a bottle, but then the bottle
4:06:28is like full and it's like sealed. That
4:06:30water has nowhere to go and so pressure
4:06:32is going to build up and stop more water
4:06:34from flowing. So, just to make sure that
4:06:35we're getting this topic right, and
4:06:36again, I don't want to go too much into
4:06:38the weeds, but this is super important.
4:06:39You should know what pressure increases
4:06:41in post-renal acute kidney injury and
4:06:43that is hydrostatic pressure. And where
4:06:45does it occur? In Bowman's space and
4:06:47then what's the immediate effect? It
4:06:48decreases the GFR. That's what's
4:06:50important. Okay, I feel like I had to
4:06:52explain that briefly. And you should
4:06:53know there are all sorts of BU creatin
4:06:55ratios. For prenal, you've got like 20
4:06:58to1 BUN to creatin. For intrinsic, it's
4:07:01less than 15. It's at 15 to1, but then
4:07:04later it's less 15 to1. So in early
4:07:06post-renal the BUN is increased because
4:07:09ura reabsorption continues and creatinin
4:07:12stays low in the serum. But don't get
4:07:14too bogged down on that. This is just
4:07:16outflow obstruction stones BPH
4:07:18neoplasms. That's what we're looking at.
4:07:20You know maybe even congenital
4:07:21abnormalities that stop that flow. It's
4:07:23postrenal. So obstruction you have
4:07:24elevated B1 to creatinin ratio. Cool
4:07:27beans. I think those are some cool
4:07:28beans. All right. Here are some of the
4:07:29answer choices. Clear cell would be a
4:07:31renal mass. High-grade cirrus. Carcinoma
4:07:33of the ovary might compress them if
4:07:35large but it's less common. Bilateral
4:07:36unless it's super big and adnocarcinoma
4:07:38of the colon you'd have change in the
4:07:39bowel habits and obstruction would need
4:07:41to be extensive and posterior. So
4:07:42cervical cancer can cause kidney failure
4:07:45because it doesn't necessarily stay
4:07:46locally. It invades the tissues next to
4:07:48the cervix and it compresses the urtors.
4:07:49So yep that's cervical cancer. All
4:07:50right. Here we have a 62-y old man. It
4:07:53could also be a female, you know,
4:07:55middle-aged. It could be a lot of
4:07:56things. I'm going to go ahead and pop up
4:07:57right here a 62-year-old man. So he's
4:08:00got a history of roheatic heart disease
4:08:01presenting with sudden onset diffuse
4:08:03abdominal pain for the last 3 hours. He
4:08:04describes the pain as 10 out of 10
4:08:05constant. On exam he's a diaphetic and
4:08:08has irregularly irregular pulse. What's
4:08:10the mechanism behind his condition? The
4:08:12answer is a mural thrombus formation and
4:08:14embleization. So it's acute meenteric
4:08:16eskemia due to embolism of the left
4:08:17atrial thrombus. He's got mitro stenosis
4:08:20and it predisposes him to thrombus
4:08:22formation. So the SMA is the most common
4:08:24abdominal vessel that gets blocked in a
4:08:26cardiac embolis and that's because you
4:08:28recognize the irregularly irregular
4:08:30results here which is AIB. So the atria
4:08:33stops contracting effectively and so the
4:08:34blood starts to pull then that causes a
4:08:37thrombus. So you can see this in several
4:08:38different ways. They could have asked
4:08:40about you know a male they have
4:08:41abdominal pain irregularly irregular
4:08:44pulse that's always going to be the case
4:08:45and every single time you see that it's
4:08:46aphib. They might say there's an opening
4:08:48snap or there's some diastolic murmur.
4:08:50That's mital stenosis, right? And on
4:08:52imaging, you could see maybe the small
4:08:53bowel and colon distension. Basically,
4:08:56what's happened is there's acute
4:08:57messenteric eskeeia. There's
4:08:58embleization, which is the procedure
4:09:00where you know block or close off a
4:09:02blood vessel using a substance called an
4:09:04embleizing agent. It's used to treat
4:09:06different conditions like abnormal blood
4:09:07vessels, internal bleeding, tumors, all
4:09:09that stuff. But the cause could be the
4:09:11embleization of the atrial thrombus due
4:09:13to aphib. So aphib causes the stasis of
4:09:15the blood in the left atrium especially
4:09:18when it's enlarged such as in mital
4:09:20stenosis and so that leads to thrombus
4:09:22formation embleization to systemic
4:09:24circulation and the superior mesenteric
4:09:26artery is super susceptible why because
4:09:29it's got high flow lot of blood going
4:09:31through there and it's also got a narrow
4:09:33angle and so you can have a sudden
4:09:34occlusion of the SMA that causes eskeeia
4:09:36and that's why the small intestine is
4:09:38having problems and the transverse colon
4:09:40are having problems it's sudden
4:09:41abdominal pain that is out of proportion
4:09:43to the exam. This is severe. In the
4:09:46question, we had severe pain. So, it's
4:09:47not it hypotension induced watershed
4:09:49infuction that affects the splenic
4:09:51flexure and the rectus sigmoidal
4:09:52junction that's seen in shock states
4:09:54affecting the lowflow areas not the SMA.
4:09:56They could also ask about hemorrhaging.
4:09:58Well, that would lead to hypoprofusion
4:10:00and non-lusive eskeemia. So, that's in
4:10:01the watershed areas like B. Basm of
4:10:03splenic arteries. That' be in cocaine
4:10:05use, intense phasic constriction and
4:10:07local thrombosis due to endothelial
4:10:08erosion. You don't have athoscerosis
4:10:10history. So, embolism is primary here.
4:10:12It's not some sort of a plaque rupture,
4:10:13right? That'd be atheroscerosis, like a
4:10:15coronary artery disease or something
4:10:16like that. And that can trigger a local
4:10:18thrombus, but it's a lot less likely in
4:10:20the embolism in somebody who has aphib
4:10:22and no athoscerotic risk factors. And a
4:10:25thrombosis is is very possible, but
4:10:27you'd have to look out for something
4:10:28like a hypercoagulable state,
4:10:29antifhospholipid syndrome or cancer. So
4:10:32it's less likely in the embolism. If
4:10:33somebody's got a that's usually going to
4:10:35be the cause of the embolism. So the
4:10:36most common artery that's affected by
4:10:38emolic acute messenteric eskemia is
4:10:40definitely the SMA. And the classic EKG
4:10:42finding is irregularly irregular rhythm
4:10:45and that's Aphib. And the valvular
4:10:47disease that predisposes you to Aphib
4:10:49and also left atrial enlargement which
4:10:52is the cause of this patient's condition
4:10:53is mitro stenosis. All right. And our
4:10:55next question we have a 60-year-old
4:10:57woman with a 10year history of poorly
4:10:59controlled type 2 diabetes. This could
4:11:01also be a man as well. So I've got my
4:11:02demographic photo representing that.
4:11:04Discomfort in the lower legs for the
4:11:06past 3 months. She says the pain is
4:11:08worse at night and describes it as
4:11:09tingling fire ants crawling up from my
4:11:11feet. She finds some relief warming her
4:11:13feet. On exam, she has decreased
4:11:16vibratory sensation and pinp pricking of
4:11:18below the knees, diminished ankle
4:11:20reflex, and intact motor strength, which
4:11:21the following describes the nature of
4:11:22her pain. The answer is burning pain.
4:11:24And what we have to do is recognize that
4:11:26male or female, what this patient is
4:11:28experiencing is called it's diabetic
4:11:30peripheral neuropathy. The most common
4:11:32type is symmetric distal sensory motor
4:11:34polyuropathy. And it's burning because
4:11:37neuropathic pain is described as burning
4:11:39or tingling, electric shocks, pins and
4:11:41needles. That's what people feel. It's
4:11:43worse at night and that's because it's
4:11:44unmasked whenever it's not, you know,
4:11:46the patient's not distracted. It's
4:11:48improved by warmth like a hot bath and
4:11:50vasa dilation can actually improve that
4:11:52micro circulation. So what we have here
4:11:54is an endocrine question, diabetes,
4:11:56diabetic complications. We have a
4:11:58symmetric distal sensory motor
4:11:59polyuropathy, glove and stocking
4:12:01distribution with burning and tingling
4:12:02pain. Stabbing is for vidiculopathy or
4:12:05localized nerve impingement. Cramping
4:12:07for muscle fatigue, aching, muscular,
4:12:09skeletal or inflammatory pain and
4:12:11tightness. Could be spasticity or
4:12:13claudication. And what's crazy is 50% of
4:12:15diabetic patients develop peripheral
4:12:16neuropathy sometime in their life. So it
4:12:18starts with just some numbness, maybe
4:12:20some tingling in the toes. Then you have
4:12:22a lot of burning pain that people
4:12:23recognize in the night time. It's not
4:12:25collicky pain that's seen in visceral
4:12:26pain like the renoccolic or bowel
4:12:28obstruction and it's like often sharp
4:12:30and the cramping itself is often due to
4:12:33muscle eskeeia or an electrolyte
4:12:35imbalance. A sharp pain is sematic pain
4:12:38and trauma, not burning or electrical
4:12:40pain. And so they might also ask you
4:12:42what type of nerve fibers are affected
4:12:44first in diabetic neuropathy. And the
4:12:46answer there is the small fibers, pain
4:12:49and temperature. That explains the
4:12:50burning pain. And those guys are the
4:12:51vibration fibers, the propriception
4:12:54fibers. And so the treatment for this is
4:12:56you give them TCAs which is kind of
4:12:59confusing at first but amipptalene is
4:13:01what you give these patients SNRIs like
4:13:04duloxitine and gabapentin or pregabulin
4:13:06but you have to avoid long-term
4:13:08treatments of like opioids those are not
4:13:10first line for neuropathic pain
4:13:12neuropathic you give them a TCA
4:13:16SNRI or gabapentin all right so diabetic
4:13:19small fibers to large fibers burning
4:13:21pain TCAs SNRIs gabapentin
4:13:24That's the lay of the land. That's what
4:13:26you need to know. All right. Next, a
4:13:2748-year-old man with a 25 packear
4:13:29history of smoking presents to his
4:13:31primary care physician with motivation
4:13:32to quit smoking. Be male, female,
4:13:34obviously. So, my demographic just
4:13:36chosen a female. He's tried nicotine
4:13:38patches and buproprion without success.
4:13:40He has prescribed a medication that
4:13:41mildly stimulates nicotenic receptors
4:13:43while simultaneously reducing the reward
4:13:45effects of nicotine. What's the
4:13:46pharmacologic classification of this
4:13:48agent? It is a partial agonist at the
4:13:50nicotinic acetylcoline receptor. So we
4:13:52have a heavy smoker, right? They could
4:13:54have tons of packs a day for a long time
4:13:56and they've tried quitting and they need
4:13:57pharmacologic help. And so the doctor
4:13:58will choose a drug that has to do two
4:14:00things. One has to reduce cravings and
4:14:02it also has to block the CNS stimulation
4:14:04from nicotine. So we needed a drug that
4:14:06acts at the nicotinic receptor but is
4:14:07not fully activated. And so we need a
4:14:09partial agonist. So they've given them
4:14:11chantics also known as vernocine. It's
4:14:14the partial agonist at that nicotinic
4:14:15acetylcholine receptor in the CNS. It
4:14:17stimulates the receptor just enough to
4:14:20reduce these cravings, but it also
4:14:22blocks the full activation of nicotine.
4:14:23So, it blunts that reward pathway. And
4:14:25so, the dual action helps people prevent
4:14:27and like reduce their withdrawal
4:14:29syndromes, but also prevents the relapse
4:14:31because it makes smoking less rewarding.
4:14:32So, pharmacologically, you have the
4:14:33psych drugs that cause the smoke
4:14:35sessation here. And it's cycling as a
4:14:37partial agonist at the nicotinic
4:14:38receptors. Now, it's not a complete
4:14:40agonist, right? Full agonist like
4:14:41nicotine itself would just activate the
4:14:43receptor fully. And so you need
4:14:45replacement therapy like patches or gum
4:14:47to do that but it would not block the
4:14:49CNS stimulation. It would just mimic
4:14:51smoking. Antagonist would block nicotine
4:14:54from binding but it does not reduce the
4:14:55cravings. Buproprion is close. It's an
4:14:57atypical anti-depressant and it's also a
4:15:00nicotinic antagonist and dopamine
4:15:01norinephrine reuptake inhibitor but it's
4:15:03not as effective at reducing those
4:15:05cravings directly. And it's not an
4:15:06inverse agonist because that's rare in a
4:15:08clinical farm and that would like do the
4:15:10opposite of the receptor activation. So
4:15:12that would even worsen the withdrawal.
4:15:13So you definitely would not use that
4:15:14there. And so we have to know for this
4:15:16question what is vernicle's mechanism of
4:15:18action and for that we have to know is a
4:15:19partial agonist of the alpha 4 beta 2
4:15:23nicotinic acetyloline receptor and what
4:15:25are the major side effects of it nausea
4:15:27vivid dreams neuroscychiatric symptoms
4:15:29like depression suicidal ideation but we
4:15:32should also know some pharmacologic
4:15:34options for smoking sensation. So we
4:15:35talked about verocine that's partial
4:15:37agonist. We also have talked about
4:15:38buproprion that's norepinephrine and
4:15:40dopamine reuptake inhibitor and also a
4:15:42nicotinic antagonist. And then there's
4:15:44nicotine replacement therapy just the
4:15:45gum and the patches that is a full
4:15:47agonist. And so the question is why do
4:15:49we care about nicotinic receptors and
4:15:51smoking sensation? Well nicotine and
4:15:52nicotinic receptors like what's the
4:15:54connection there? Because nicotine binds
4:15:56and stimulates the nicotinic
4:15:57acetylcholine receptors in the central
4:15:59nervous system, right? That's how
4:16:00nicotine works. And so nicotine is an
4:16:02exogenous agonist at the CNS nicotenic
4:16:05receptor. And so you have a dopamine
4:16:06release because of that and that causes
4:16:08the addiction. It's the dopamine
4:16:10release. The nicotine exogenous
4:16:11influence nicotinic receptors nicotine
4:16:13nicotinic dopamine that's the whole
4:16:15stick. And so nicotine crosses that BBB
4:16:18the bloodb brain barrier and it binds to
4:16:19the alpha 4 beta 2 subtype of the
4:16:22acetylcoline receptor in the vententral
4:16:25tegmental area the VTA and that leads to
4:16:27the dopamine release into the nucleus
4:16:29encumbent. And then you have reward.
4:16:31You're like oh my gosh I really love
4:16:32that sensation. And so verenocine helps
4:16:34because it's a partial agonist at the
4:16:36alpha 4 beta 2 receptor of the nicotinic
4:16:38acetylcoline receptor and it stimulates
4:16:40just enough to reduce those cravings.
4:16:41It's a partial dopamine release. It's
4:16:43like okay I kind of like that but it
4:16:44also blocks the nicotine from binding
4:16:45right. So it blunts the four the full
4:16:47reward and so you get less withdrawal
4:16:49less reinforcement if you relapse and
4:16:51it's easier to quit. So verocine partial
4:16:53agonist at the nicotinic acetylcoline
4:16:55receptor cool beans got to reduce those
4:16:57cravings got to block that nicotinic
4:16:58reward. All right, our next question. We
4:17:00have a 42-y old man presenting with 10
4:17:01days of severe right-sided headaches.
4:17:04The last 20 to 40 minutes. He says the
4:17:05pain is excruciating. Centered behind
4:17:08his eye occurs daily at 2 a.m. waking
4:17:10him from sleep. So, this is recurrent
4:17:12unilateral short duration severe
4:17:14headache with autonomic features like
4:17:15trigger pattern with alcohol and also
4:17:18like a nocturnal timing. So, all these
4:17:20things are pointing us to a cluster
4:17:21headache and that is indeed our answer.
4:17:23So, we have recurrent short duration
4:17:25severe headaches. Often times what
4:17:26they'll do is they'll pick a side.
4:17:27Usually they'll say like h we got the
4:17:29left side it's like 30 60 minutes it
4:17:30occurs daily usually at night there's
4:17:32some tearing and redness of the eye and
4:17:34it's ipsilateral there's nasal
4:17:35congestion that's also and then when we
4:17:37drink alcohol it causes more pain to
4:17:39occur. So basically what we usually look
4:17:41out for for a cluster headache is
4:17:42unilateral and severe and it's behind
4:17:45the eye or the temple and it's
4:17:46associated with autonomic symptoms on
4:17:48the same side. So think lacrimmation,
4:17:51conjunctival injection, nasal
4:17:53congestion, rhinora and sometimestosis
4:17:55or meiosis like partial horner syndrome
4:17:57and it occurs in clusters. You should
4:17:58also know that 100% oxygen is abortive
4:18:00and verapamil is prophylactic. So
4:18:03migraine with autonomic features these
4:18:04are longer 4 to 72 hours and not male
4:18:07predominant. Proxismal hemicrania
4:18:09response to endamethasin that's going to
4:18:10be rare in men and also you're really
4:18:12not going to see that tested on step
4:18:14one. Many more frequent attacks would be
4:18:15seen there. Trigeminal neuralgia would
4:18:17have electric shock pain that's
4:18:18triggered whenever you touch something.
4:18:20Temporal arthritis is jaw claication and
4:18:22the ESR would be elevated and here you
4:18:24have vision changes as well. So alcohol
4:18:26is the trigger but it's not the
4:18:27pathogenesis involves the hypothalamic
4:18:29activation not just vasoddilation.
4:18:31Allergic rhinitis can mimic some of the
4:18:32symptoms like lacrimmation and
4:18:34congestion but it's usually mild not
4:18:36painful just it's not just basic
4:18:38allergies right there's no like severe
4:18:40headache there it's not triggered by
4:18:41alcohol would not be non-epotic and it's
4:18:44not like a CNS neoplasia cuz there you'd
4:18:46have the brain tumors that are
4:18:47progressive and constant dull headache
4:18:48and it's often worse in the morning or
4:18:50with a balva maneuver and it would not
4:18:52cause a reproducible short sharp daily
4:18:54attack especially wouldn't have ips
4:18:55lateral autonomic symptoms and that
4:18:57giant cell arthritis we talked about
4:18:59another big factor there is it occurs in
4:19:01patients that are greater than 50 years
4:19:03old. Headache is often diffuse and it's
4:19:04localized to the temples and it seem
4:19:06with jaw claudication, vision loss and
4:19:08elevated ESR levels. This patient is
4:19:10actually pretty young relatively
4:19:11speaking and so it's not going to be a
4:19:15jaw claudication issue with temporal
4:19:17arthritis giant cell arthritis. So yeah,
4:19:20the first line abort of treatment for
4:19:22the cluster headache is 100% oxygen.
4:19:23Give them a non-rebreather mask and
4:19:25first line prophylactic is vapamil. And
4:19:27what helps you distinguish this from
4:19:28other headaches? If you have a male is
4:19:30greater than female, nocturnal onset,
4:19:31seasonal pattern, and the pain is like
4:19:34super super severe. That's cluster
4:19:35headache. All right. Here we have a
4:19:362-year-old boy. Could be a girl as well.
4:19:38So, I have given the demographic picture
4:19:40of a girl. Looks like she's tugging on
4:19:41her ear. She's got some fussiness, runny
4:19:44nose and cough. Pulls your ear and she
4:19:45cries. Which the following describes the
4:19:47anatomical route? The answer is ferx to
4:19:49the auditory tube to the middle ear.
4:19:50This is acuteitis media because it
4:19:52travels in the nasop ferinx to the
4:19:54middle ear of the via the auditory tube.
4:19:56In young children, inflammation traps
4:19:58and you get the infection. So oftent
4:19:59times they have a history of chronic
4:20:00otitis media and they have a sore
4:20:02throat, mild cough, ear pain,
4:20:04irritability, they pull on their ear,
4:20:05that that kind of stuff. There's usually
4:20:07some fluid behind the tempanic membrane
4:20:09and all of that leads you to think of
4:20:10acute otitis media. And so you have to
4:20:12know the way that that spreads. So the
4:20:14ustation tube is another word for the
4:20:16auditory tube. And that's why students
4:20:18will miss this particular topic because
4:20:20they don't realize the station tube is
4:20:22the auditory tube and it connects the
4:20:23nasop ferinx to the middle ear. And so
4:20:25in children, you have a really tiny
4:20:27short and wide tube and it's more
4:20:30horizontal than in adults. And that
4:20:33makes it easier for upper respiratory
4:20:35infection pathogens to ascend from the
4:20:36nasop fernx into the middle ear. And so
4:20:39you have the result of fluid
4:20:40accumulation and inflammation which is
4:20:43you know going to lead to otitis media.
4:20:44So this is just like head ear nose and
4:20:46throat question otitis media infection
4:20:48of the middle ear. The pathogens ascend
4:20:50from the nasop ferinx via the ustation
4:20:51tube to the middle ear. It's not the
4:20:53lenop ferinx. The ustation tube connects
4:20:55to the middle ear, not the inner ear.
4:20:57Oro oro ferinx there's no communication
4:20:59like that. Nasal is unrelated to the
4:21:01cookia. Tracheal is part of the lower
4:21:03respiratory tract. There's no direct
4:21:05connection to the estian tube and
4:21:07mastoid to middle is adjacent to the
4:21:08middle but the secondary sites of
4:21:09infection. And this is actually super
4:21:11common. 80% of children are going to
4:21:12experience at least one episode of
4:21:13theitis media in their life by the age
4:21:15of three. It's that horizontal
4:21:16construction in the young little kids,
4:21:19the shorter ear, the wider ear, the
4:21:21horizontal ear, all that stuff.
4:21:22Acuteitis media goes through the
4:21:24estation tube to the middle ear. All
4:21:25right. If anybody asks, just say that my
4:21:27numbers are modern art because that is a
4:21:29wonky looking three. In this question,
4:21:30we have 800 adults after 3 months 180 in
4:21:33the intervention and 40 skip multiple
4:21:35sessions. We want to see the primary
4:21:36outcome based on the original group.
4:21:38This is intention to treat. So you
4:21:40analyze all based on the initial group
4:21:41allocation. This is super simple. It's
4:21:43just intention to treat analysis. All
4:21:45participants are analyzed in groups that
4:21:47they were in originally. That's all
4:21:49there is to this. It's super simple.
4:21:51intention to treat. Moving on to the
4:21:52next one. All right. Step one loves to
4:21:54ask about anastmosis. We have a
4:21:5668-year-old man with a history of
4:21:57hypertension and smoking undergoing
4:21:58elective open surgical repair of the
4:22:00infraal abdominal aortic aneurysm.
4:22:02Interoperatively, the left testicular
4:22:04artery is liated to allow vascular
4:22:06access. Postoperatively, he has no signs
4:22:08of testicular eskeeia. Which artery is
4:22:10most likely maintaining profusion to the
4:22:12left testes? All right. So, the key to
4:22:14this question is knowing where the
4:22:15testicular artery originates and who
4:22:16backs it up when it's lost. The answer
4:22:18is the artery to the ductus deference.
4:22:20If the testicular artery is damaged or
4:22:22liated. So this is just anosis question.
4:22:24So here's the explanation. Superior
4:22:25vicular artery supplies the dome.
4:22:27Internal pudental gives rise to the
4:22:29scrutal branches but not anosis with the
4:22:31testes. Middle rectal artery supplies
4:22:33the rectum. Superficial epigastric is a
4:22:35branch of the femoral artery. Supplies a
4:22:36lower abdomen. All right. So this is
4:22:37just an anastmosis question. And on the
4:22:39sub exam you can see a lot of these
4:22:40anastasmosis questions like there's the
4:22:42SMA to the IMA. If you have a AAA repair
4:22:45then the IMA is sacrificed. So you need
4:22:46the SMA collaterals. Here's a practice
4:22:49question about that. Basically, a guy
4:22:50under goes a procedure. What do you do?
4:22:52Middlecolic via the arc of realin.
4:22:55That's the collateral pathway for the
4:22:56middlecolic artery. So, just just know
4:22:57that the SMA touch the IMA. And there
4:22:59are all sorts of anastasis to know like
4:23:01GI tract, SMA, IMA, ciliac with SMA,
4:23:04portal with systemic. You have esophagus
4:23:07the esophageal esophageal veraces.
4:23:09Rectum the analctyl veraces and the
4:23:11umbilicus, the capet medusa, that's the
4:23:13parameical with the epigastric. Rectum
4:23:15has the superior rectal with the middle
4:23:16inferior and left gastric with the
4:23:18azygus. The pelvic reproductive you have
4:23:20ticular ovarian artery with the artery
4:23:22of the ductus deferrons or the uterine
4:23:24artery. So uterine ovarian artery
4:23:26abducted deferrons ticular. Know those
4:23:28two things together. Uterine artery
4:23:30ovarian artery in a hyerectomy liation
4:23:32of uterine artery must spare the urer
4:23:34and ovarian artery preserves the
4:23:36profusion to the ovary. In the thoracic
4:23:38wall you have internal thoracics and
4:23:39intercostals bronchial and pulmonary
4:23:41arteries. In the lower limb you have
4:23:42inferior epigastric and superior. The
4:23:44deep circumlex with the ilio lumbar
4:23:47supplies the iliac crest. The brain has
4:23:48the circle willis anterior and posterior
4:23:51communicating arteries. And so here's a
4:23:52big old list. These are all the
4:23:54anastasimosces that you probably need to
4:23:55know on test day. Celiac SMA ovarian
4:23:58uterine portal systemic sma
4:24:00bronchopulmonary IMA external iliac
4:24:03thoracic intercostals. If you guys found
4:24:06this helpful then please consider liking
4:24:08and subscribing and we'll see you guys
4:24:09in the next video. Hello everybody.
4:24:10Welcome back. We're on MBME 29141. These
4:24:13are all original questions. Here we go.
4:24:15A 55-year-old woman with long-standing
4:24:18history of autoimmune hepatitis presents
4:24:19with confusion and irritability. Now, in
4:24:21this question, we have a woman, but in
4:24:22the relevant demographic, I've displayed
4:24:24a man. And that's just to demonstrate
4:24:25how you shouldn't be locked into the
4:24:27female demographic for this particular
4:24:28condition. But I'm going to go ahead and
4:24:30change it to a female. Now, we can
4:24:32visualize this patient. Her daughter
4:24:33reports the patient was recently treated
4:24:35for cellulitis and hasn't had a bowel
4:24:36movement in 3 days. Vital signs are
4:24:38stable. On exam, she is disoriented and
4:24:40has flapping tremor when asked to extend
4:24:42her arms. Her abdomen is distended. Lab
4:24:44show A of 86. ALT of 74. Ammonia is 118.
4:24:47B1 is a 10. Codin is 0.9. Which of the
4:24:50following best explains her symptoms? So
4:24:52that flapping tremor is called astrixis.
4:24:54And the correct answer to this question
4:24:55is hypermonia.
4:24:57It's a paddic encphylopathy triggered by
4:24:59constipation and infection leading to
4:25:02elevated ammonia and CNS toxicity.
4:25:04Asterexis is the key sign that flapping
4:25:07hand tremor and that is due to metabolic
4:25:08encphylopathy which is most often from
4:25:10hyperammonia. Now you can also see
4:25:12cerosis that's portoymic shunting and
4:25:14decreasing the ammonia clearance and if
4:25:16you decrease the ammonia clearance then
4:25:18some of it can actually cross the bloodb
4:25:20brain barrier and that can cause
4:25:21astroite swelling and then cerebral
4:25:23edema and so the symptoms that you'll
4:25:25see in a patient who has this disorder
4:25:27or who has a lot of ammonia would be
4:25:29confusion drowsiness asterxis sigma
4:25:32cerosis like jaundice spider anga escap
4:25:35medus some things that precipitate this
4:25:38are GI bleeds infections hypocalemia
4:25:41constipation, sedatives and for
4:25:43treatment you give them lactulus and
4:25:45refaxamon to reduce the gut florammonia
4:25:47production. So if you see that flapping
4:25:48tremor and cerosis sigmata and altered
4:25:51mental status then it's going to be
4:25:52hypermonia or hpatic and encphylopathy
4:25:54and that can be the case even if they
4:25:56don't literally give you the ammonia
4:25:57levels. So just to make sure we got this
4:25:58down, a question that you should be able
4:26:00to answer is what is the pathophysiology
4:26:02of aststeris in cerosis and that's the
4:26:04buildup of ammonia, right? It's the
4:26:05impaired aststery metabolism and the
4:26:07aststerytes are the gleal cells which
4:26:10are non-neuronal cells that support and
4:26:12protect the neurons in the central
4:26:14nervous system you know the brain and
4:26:15the spinal cord. You should also know of
4:26:17some other systemic conditions besides
4:26:19liver failure that can cause arexis and
4:26:21that would be renal failure uremia and
4:26:23hypercapneia which is CO2 retention. So
4:26:25let's talk about the difference between
4:26:26hpatic and sephylopathy and you do need
4:26:28to know this for step one and uremic
4:26:29encphylopathy or renal failure. So in
4:26:31hpatic you start with the cerosis that
4:26:33leads to a CO2 necrosis causing dismia,
4:26:37confusion, sinosis, COPD exacerbation
4:26:40and asterisics can be seen there. But
4:26:42those are the only causes on step one
4:26:45that would lead to asteristics which is
4:26:46the flapping tremor. And it's actually
4:26:48defined as the sudden brief lapses in
4:26:51sustained posture whenever like the hand
4:26:53is flapping whenever the arms and wrists
4:26:55are extended. But I would conceptualize
4:26:57this as metabolic encphylopathy.
4:26:59Encphylopathy is just a fancy way of
4:27:01saying conditions that affect the
4:27:03function of the brain and cause changes
4:27:05in the mental state. Anything that
4:27:06disrupts the brain's normal activity and
4:27:08leads to symptoms like confusion,
4:27:09altered consciousness and seizures would
4:27:11be classified as an encphylopathy. So
4:27:13that could be infections, you know,
4:27:14viral like encphilitis, bacterial like
4:27:17menitis or even parasitic infections. It
4:27:19could be trauma, you know, head injury,
4:27:21stroke, tumors, autoimmune disorders,
4:27:23you know, multiple scerosis, lupus, and
4:27:25even genetics. But in sephylopathy most
4:27:27commonly would be confusion, altered
4:27:29mental state, seizures, memory problems,
4:27:31difficulty speaking and understanding
4:27:32language, that sort of thing. Usually
4:27:34when we diagnose it, we do blood tests
4:27:35for infections, metabolic imbalances,
4:27:38and imaging studies due to CT or an MRI
4:27:40of the brain to rule out structural
4:27:41abnormalities. And you can also get an
4:27:43EEG that monitors the brain activity and
4:27:45detect seizures. All right, that about
4:27:47wraps it up. Let's go to the next
4:27:48question. 142. We have a 68-year-old
4:27:50woman with a history of chronic insomnia
4:27:52and weight loss is started on
4:27:53acetylopram after being diagnosed with
4:27:56major depressive disorder. This
4:27:57medication primarily enhances the
4:27:59serotic signaling from neurons located
4:28:01at which structure? Well, it's
4:28:02serotonin, the Ralph nuclei. So, SSRIs
4:28:05inhibit the reuptake of serotonin. We
4:28:07all know this. And the Ralph nuclei is
4:28:09the primary search nuclei. And so, you
4:28:11should really pick this with anything
4:28:13related to serotonin. Now, you have cell
4:28:14bodies in the midline brain stem
4:28:17reticular formation like the midbrain,
4:28:18the pawns, and the the medulla. And the
4:28:20neurons here convert L tryptophen to
4:28:23serotonin 5HT. And they project widely
4:28:25to the cortex, the hypocampus, the
4:28:26hypothalamus, and the spinal cord. So
4:28:28fuoxitine, serotillene, peroxitine,
4:28:31those guys all block the serotonin
4:28:33transporter and so you increase the
4:28:34serotonin in the synaptic cleft that
4:28:36obviously increases increases your
4:28:37sleep, your appetite regulation. So
4:28:39serotonin is synthesized in the raph
4:28:41nuclei. So here I've updated the patient
4:28:42demographic for this question. Here's
4:28:44some trap answers why they're wrong.
4:28:45VTA's dop is dopamineergic involved in
4:28:47the reward. We had a question about that
4:28:49on our last set of 10. Hypothalamus
4:28:51regulates homeostasis but not the source
4:28:53of serotonin. The locus curious produces
4:28:55norepinephrine. Nucleus bacillus isurgic
4:28:58so it's important in Alzheimer's. This
4:29:00is just depression. You should know the
4:29:01mechanism of serotonin causing 5HT to
4:29:03stay longer on the cleft. El tryptophen
4:29:05is a metabolic precursor for serotonin
4:29:07synthesis. Okay, for the next question,
4:29:09it could be a man or a woman. Here we
4:29:10have a 41-year-old man with chronic
4:29:12tension type headaches has started on a
4:29:14new medication for prophylaxis. One week
4:29:15later, he presents with abdominal
4:29:17bloating, constipation, and difficulty
4:29:19urinating. Vitals are stable. He has dry
4:29:20mucous membranes and decreased bowel
4:29:22sounds on exam. Neurologic exam is
4:29:24normal. Which of the following
4:29:25neurotransmitter effects is most likely
4:29:28responsible for his current symptoms? So
4:29:30here's our patient demographic though it
4:29:32could be a female and our answer is D.
4:29:33Miscarinic acetylcholine receptor
4:29:35blockade. So they have constipation and
4:29:36dry mouth and urinary retention. Those
4:29:38are antiolinergic symptoms and this
4:29:40could be because they use a tricyclic
4:29:42anti-depressant to stop the headache.
4:29:43TCA's block mucinic receptors. Now, this
4:29:45is really interesting because the
4:29:47question stem is going to give you
4:29:48constipation and they're going to give
4:29:50you urinary retention and that they
4:29:52started a new anti-depressant or they'll
4:29:54have you infer the anti-depressant.
4:29:56Feeling blue started on something new,
4:29:57constipation, urinary retention. Okay?
4:30:00So, all these things are happening at
4:30:01once and you have to know the mechanism
4:30:02of action because they're not going to
4:30:03ask like which neurotransmitter blockade
4:30:05is is actually causing this. And so,
4:30:07tricyclic anti-depressants, these are
4:30:09known as TCAs. They are less selective
4:30:12and so they block a lot of things. They
4:30:14block 5HT and norepinephrine uptake and
4:30:17that's the therapeutic part of it,
4:30:18right? They're misuscreen acetylcoline
4:30:20receptor blockers and that is going to
4:30:22contribute to the side effect profile.
4:30:24You typically don't want those but
4:30:25that's how they're going to test you
4:30:27because of that constipation that
4:30:28urinary stuff is because of that
4:30:29miscarrenic acetylcholine receptor stuff
4:30:31and it's because the TCAs which were
4:30:32taken for depression. So the depression
4:30:34was treated with TCAs. The TCA is caused
4:30:37through the blocking of miscinic stuff,
4:30:38the constipation and the urinary
4:30:40symptoms. That's the way these problems
4:30:41work and that's why I think they're kind
4:30:43of interesting. They're good questions.
4:30:44Now, they also can block the histamine
4:30:46and these are H1 receptors and that
4:30:48causes sedation and weight gain. They
4:30:50block alpha 1 adinurics. They block the
4:30:53mucus and that causes the anticolinergic
4:30:56effects, the urinary retention,
4:30:57constipation, the dry mouth. And they're
4:30:59going to try to get you. They always
4:31:00anytime you see a question about TCAs,
4:31:02they'll try to trick you in all sorts of
4:31:04ways. One of them that they love asking
4:31:05is dopamine. And dopamine is blocked by
4:31:07antiscychotics causing extra pureal
4:31:09symptoms. You might see some
4:31:10hyperproinia but not constipation and
4:31:13urinary problems. So it's not going to
4:31:14be dopamine associated. And let's look
4:31:16at the answers here. So dopamine
4:31:17antagonism would be antisycchotics not
4:31:20constipation. Alpha 1 blockade causes
4:31:22orthostatic hypotension. H1 antagonism
4:31:24sedation weight gain. And GABA agonism
4:31:26would be benzo and barbs sedation but
4:31:29not anticolinergic effects. So yeah
4:31:31anti-depressants can make you stop
4:31:32pooping at least TCAs. All right. So
4:31:34those are the buzzwords. Dry mouth
4:31:35urinary retention constipation hot as a
4:31:37hair dry as a bone blind as a bat red as
4:31:39a beat as a hatter anticolinergic
4:31:41toxidrome pneumonic elderly patient
4:31:43they're super sensitive to it TCAs the
4:31:45tryptoines for MDDD also for migraine
4:31:48prophylaxis and the blocking of the H1
4:31:50receptors can cause that sedation and
4:31:52the alpha 1 adonergic blockade causes
4:31:54orthostatic hypotension there's the
4:31:56pathophys that we kind of talked about
4:31:57is blocking the mucus receptors and so
4:32:00you have less contraction of the bladder
4:32:01less paristalsis and that would be
4:32:03urinary retention and constipation
4:32:04respectively blockage of the salivary
4:32:06glands that's the dry mouth and the
4:32:07central effects of delirium and
4:32:09confusion in the elderly. I think we
4:32:10covered that question pretty thoroughly.
4:32:11Okay, so the next question we have a
4:32:1328year-old Olympic sprinter who has
4:32:16undergone muscle performance testing.
4:32:18During the experiment, her vasis
4:32:20lateralis is electrically stimulated to
4:32:22contract to contract under isotonic
4:32:24conditions at varying loads. Researchers
4:32:26observe the maximum shortening velocity
4:32:27of the muscle does not increase beyond a
4:32:29certain point despite higher frequencies
4:32:30of stimulation and sufficient ATP
4:32:32availability. What determines the
4:32:33maximum velocity of muscle fiber
4:32:35shortening under these conditions? The
4:32:37answer is meosin ATPA's activity. Now
4:32:39here I actually want to go up to the
4:32:40buzzwords first. Crossbridge cycling you
4:32:42know about the actin the meosin heads.
4:32:43ATP hydraysis is required to reset the
4:32:46meosin and isotonic contraction is when
4:32:48the muscle shortens under constant
4:32:50tension. And the rate limiting step here
4:32:52is how fast meosin can detach and
4:32:54reccock and reattach. It's biochemical.
4:32:56It's not electrical. Type two is the
4:32:58fast fibers. Higher measin ATP's
4:33:00activity. Thyroid hormone increases
4:33:01expression of the fast meosin heavy
4:33:03chains and so faster ATPAS causes faster
4:33:05detachment and attachment and quicker
4:33:07shortening. And here's the motor neuron
4:33:08fires. Acetyloline is released into the
4:33:10neuromuscular junction. Then it
4:33:11deolarizes calcium is released exposes
4:33:14the actin. Meosin binds the actin power
4:33:16stroke. Sarccomir shortens. ATP binds
4:33:19meosin detaches from actin hydrayzeed
4:33:21restocks. And so it's the rate of the
4:33:22shortening that affects the rate of the
4:33:23cycle. Now isotonic contraction is when
4:33:25the muscle generates a constant tension
4:33:28while the length is changing. That's
4:33:29isotonic contraction. There's
4:33:30concentric, that's muscle shortening
4:33:32while contracting. And there's
4:33:33eccentric, that's muscle lengthening
4:33:34under the tension. The speed of
4:33:36shortening is determined by how fast the
4:33:39cross bridges cycle between actin and
4:33:41meosin. I remember they tested me on the
4:33:42actin measin binding. In one of my
4:33:44biology classes at Harvard, we had to
4:33:46list all of the subs to the cycle. And I
4:33:48think that's overkill. But I would say
4:33:50one of the most important things to know
4:33:51is that first you have the meosin and
4:33:53the ADP the binding of the actin the
4:33:55crossbridge formation and then ATP binds
4:33:58meosin and that's the detachment phase
4:34:00and then you have ATP hydrarolysis and
4:34:02that's where the meosin is reccocked and
4:34:04the cycle will repeat. So faster ATP
4:34:07binding and hydrarolysis means you have
4:34:08faster measin cycling which means you
4:34:10have faster sarccomir shortening and so
4:34:12the rate of the crossbridge turnover
4:34:14determines the max velocity of the
4:34:15isotonic contraction. Wow, we got in the
4:34:17weeds there. Let's make this super
4:34:18simple. Isotonic contraction are the
4:34:20changes in length under constant load.
4:34:22The speed is determined by how fast the
4:34:25cycle happens. Faster cycle, faster
4:34:27shortening. Okay, three things we need
4:34:28to know. What determines max velocity?
4:34:30That's the rate of the cycling, the ATP
4:34:31turnover. And in smooth muscle, why is
4:34:34contraction slower? That's because the
4:34:35cycling is slower, which allows for
4:34:37sustained tone. Okay? And if any of you
4:34:39guys are like, "Oh my gosh, what's going
4:34:41on?" Then look at these buzzwords right
4:34:43here. And you see this right here
4:34:44lifting a dumbbell. That's where the
4:34:46muscle shortens while you're holding a
4:34:48constant weight. That would be isotonic
4:34:49contraction. The muscle is shortening
4:34:51while holding a constant weight. What
4:34:52makes the muscle shorten? The meosin
4:34:54pulls the actin. That causes the
4:34:55sarcimeir to shorten and then the muscle
4:34:57shortens. What controls the speed of
4:34:59that though? Well, the speed is how fast
4:35:01the meosin head can grab the actin, pull
4:35:03and do the power stroke, let go, you
4:35:06know, where the ATP binds and then reset
4:35:08and try again. That cycle is called the
4:35:10crossbridge cycle. And so faster
4:35:12recycling means faster shortening. And
4:35:13they can try to trip you up in all sorts
4:35:15of ways. They could ask about the action
4:35:16potential amplitude, the frequency.
4:35:18Well, the amplitude is just all or
4:35:20nothing, right? It doesn't change how
4:35:21fast the contraction happens. The
4:35:23frequency, more frequency would just
4:35:25mean stronger force, not faster
4:35:27shortening. And it actually does not
4:35:28involve your sodium potassium ATPs
4:35:31because that's just involved in the
4:35:32maintenance of the ion balance, not the
4:35:34contraction speed itself. So the big
4:35:36takeaway here is the maximum rate of
4:35:38muscle shortening depends on how fast
4:35:41the meosin heads cycle cross bridges
4:35:43with actin and that's powered by ATP. So
4:35:46if you choose ATP on that you'll be
4:35:47right. The force is how many cross
4:35:49bridges are working and the speed is how
4:35:50fast the crossbridge cycles. All right
4:35:52this could be a boy or a girl. Here we
4:35:54have a six-month-old girl is evaluated
4:35:56for macroephily and delayed motor
4:35:58milestones. Her parents report she's
4:36:00unable to sit, unsupported and has poor
4:36:02head control. Physical exam shows
4:36:04hypotonia and increased head
4:36:06circumference. Neurologic exam reveals
4:36:08downward gaze and increased limb tone.
4:36:10MRI of the brain demonstrates a large
4:36:12fluid-filled cavity in the place of the
4:36:13cerebellar vermis. Enlargement of the
4:36:16fourth ventricle, elevation of the
4:36:17tentorium. Which of the following
4:36:18embryological structures is most likely
4:36:20implicated in this patient's condition?
4:36:21And we have all these classic answers.
4:36:23So we unfortunately have to know the
4:36:24step one embryology chart for the brain
4:36:26vesicles and the adult derivatives. Now
4:36:28the dianphylon is derived from the
4:36:30proenphylon. The adult structure that is
4:36:32formed is the phalamus and the
4:36:33hypothalamus and the retina and this is
4:36:35from the third ventricle. The
4:36:36misinphylon is derived from the
4:36:38misphylon and the adult structure that's
4:36:40formed would be the midbrain and you
4:36:42should and you should assoc and you
4:36:43should associate the misphylon with the
4:36:46cerebral aqueduct. The metanflon is
4:36:48derived from ramenflon and that gives
4:36:50rise to the pawns and the cerebellum and
4:36:53that's the upper fourth and the
4:36:54telensephylon is derived from the
4:36:56proenphylon and that forms the cerebral
4:36:58hemispheres basil ganglia and it's
4:37:00associated with the lateral ventricles.
4:37:02Okay. So the metanflon would be
4:37:04associated with your pawn cerebellum
4:37:05fourth ventricle that's dandy walker.
4:37:07The misenflon the midbrain that'd be
4:37:09associated with cranial nerve three four
4:37:11nuclei and the cerebral aqueduct
4:37:12obstruction so hydrophilis. The
4:37:14dianphylon would be the phthalamus, the
4:37:16hypothalamus and the retina. And there
4:37:18you'd see like cranoparrenioma
4:37:20compressing the hypothalamus. And the
4:37:21telensphylon defects in the telenphylon
4:37:23would cause hollowosenphily. And so if
4:37:25the question mentions the cerebellum and
4:37:26the fourth ventricle, then you should
4:37:27think of the metflon. And if it mentions
4:37:29the cerebral hemispheres, the lateral
4:37:31ventricles, you should think of the
4:37:32telenphylon. L for lateral, tel
4:37:34andphilon, lateral ventricles,
4:37:36telenphylon, lateral ventricles,
4:37:38midbrain, M for midbrain. And so here
4:37:40it's the cerebellum and the fourth
4:37:42ventricle that we're talking about. And
4:37:43so it is the metanflon. This is Dandy
4:37:45Walker malf for failed development of
4:37:47the cerebellar vermis. They're the trap
4:37:49answers and why they're wrong. And so
4:37:50the hindb brain, specifically the
4:37:53medphylon, is supposed to form the
4:37:55cerebellum in the fourth ventricle, but
4:37:56it's not here. All right. Next, we have
4:37:57a six-year-old boy presenting with
4:37:59evaluation due to rapidly growing
4:38:01nodular lesions on his scalp and cheeks.
4:38:03His parents mentioned that he's allergic
4:38:04to the sun. Reminds me of bench warmers.
4:38:06And had frequent blistering sunburns
4:38:07after brief outdoor play during infancy.
4:38:09All right, this could be a female as
4:38:11well, but I'm going to go ahead and give
4:38:12you both. So I'll generate a photo of
4:38:14this patient over here. There we go.
4:38:16Which of the following DNA processes is
4:38:18most likely defective in this patient?
4:38:19Blistering sunburns. All right. This is
4:38:21zerodma pigmentotosum. How do I know?
4:38:23Early onset photosensitivity and
4:38:25increased cancer risk. You'll see
4:38:26recurrent blistering, severe sunburns
4:38:28after sun exposure. That's why they said
4:38:30he's allergic to the sun. Also
4:38:31freckling, dry atrophic skin. And the
4:38:34mechanism for this is kind of one you
4:38:35just memorize. In fact, one of the
4:38:36earliest videos of the 790 I have on my
4:38:38channel was about nucleotide excision
4:38:40repair. Now how this works I'll go over
4:38:42to 146 is it starts with the sun right
4:38:45the sun has UV light and that forms
4:38:47peritamine thyodine dimer and nucleotide
4:38:50excision repair removes those so it's
4:38:52doing a great job removing those and the
4:38:54mechanism is endonuclease cuts out the
4:38:56damaged DNA segment DNA polymerase fills
4:38:59in that gap and DNA liase seals the
4:39:01strand that's the mechanism by which
4:39:03nucleotide excision repair deals with
4:39:06the formation of peritamine DRS by UV
4:39:08light but if you have a defect there
4:39:10then your pit amine dimers will persist
4:39:12and you have mutations and skin cancer.
4:39:14The sun is indeed a deadly laser and so
4:39:16this occurs in the G1 phase of the cell
4:39:18cycle and you see skin cancer in
4:39:21children. I would have designed it
4:39:22differently but it was not up to me and
4:39:24they'll try to get you with different
4:39:25answer choices. For instance, base
4:39:27excision repair. What's that all about?
4:39:29Well, that's just fixing the damaged
4:39:30bases, right? The deamination of
4:39:32cytosine to uricel, not UV dimers. They
4:39:34could also get you with mismatch repair.
4:39:36That fixes the DNA replication errors.
4:39:38And anytime you see mismatch repair, you
4:39:40should immediately be thinking of lynch
4:39:41syndrome. ATM kynise at taxexia
4:39:44tangactasia. You'll see recurrence
4:39:46infections and cerebellar atrophy.
4:39:48Exonucleus proof reading. That'd be
4:39:49errors in DNA replication, not the UV
4:39:51damage. Base excision would be from
4:39:53oxidative and alkalated base damage.
4:39:55Mismatch repair, microatellite
4:39:57instability, think lynch. So if you see
4:39:59on test day a kid who's not old enough
4:40:01to even ride a bike and he already has
4:40:02skin cancer, then what's actually
4:40:04happening is zeroderm pigmentotosum.
4:40:06There's the path of fizz that I kind of
4:40:08spelled out earlier. You accumulate
4:40:09those enco genes in the tumor suppressor
4:40:11mutations because that neer pathway does
4:40:14not identify the bulky lesions and
4:40:16remove them via endonucleus. So you can
4:40:18definitely see endonucleaz as an option
4:40:20here. In fact, I believe in the world
4:40:22bank there is a question where the
4:40:24answer is endonucleases and it's
4:40:25zerodmap pigmentotosum. You can see why
4:40:27that's how they ask about this condition
4:40:29UV light exposure. How do you get rid of
4:40:30them? Endonucleus activity but it's
4:40:32defective here. So you get skin cancer
4:40:34in a young kiddo. All right, next
4:40:35question. Okay, here there is a
4:40:3769-year-old man with diabetes. It could
4:40:39be a female as well, probably a similar
4:40:41age though undergoing emerent
4:40:43perccutaneous coronary invent
4:40:44intervention for an inferior ST
4:40:46elevation myioardial inffection.
4:40:48Coronary angography reveals a left
4:40:50dominant circulation and critical
4:40:52stenosis in the vessel refusing the
4:40:54diaphragmatic surface of the heart and
4:40:56atrial ventricular node. They plan to
4:40:57place a stent through which vessel must
4:41:00the catheter pass in order to reach the
4:41:01affected vessel. All right, I'm going to
4:41:02update the patient demographic so you
4:41:04can see this particular patient that
4:41:05we're talking about. Here he is. Nice
4:41:07guy. All right. Now, this question is
4:41:09easy to miss unless you have all of the
4:41:12blood supply of the heart down pat. We
4:41:13have to go from the left coronary artery
4:41:15to the posterior descending. Now, the
4:41:16way to think about this for exams is a
4:41:18right dominant heart is different from a
4:41:19left dominant heart. And in right
4:41:21dominant, the RCA gives rise to the PDA.
4:41:24But in a left dominant heart, the left
4:41:25circumlex gives rise to the PDA. That's
4:41:27the difference. And if it's co-ominant,
4:41:28then both the RCA and the left circumlex
4:41:31contribute. So there's a patient with a
4:41:32left dominant circulation and so the
4:41:33catheter has to be put in the circumlex
4:41:35and then it goes to the PDA. It's kind
4:41:37of like a memorization thing. Now if
4:41:38it's right dominant then sure it's just
4:41:39the right coronary artery. That's 85% of
4:41:41the cases. The RCA supplies the PDA and
4:41:43the AV node. But in left dominant the
4:41:45left circumlex supplies the PDA and the
4:41:47AV node. Now I want to make this simple
4:41:49for every single heart supply question
4:41:51that you ever get in the future. Let's
4:41:52name the arteries. For instance, here we
4:41:54have the anterior intervententricular
4:41:56artery LA and that supplies the anterior
4:41:59left ventricle wall, the anterior 2/3 of
4:42:01the interventricular septum. So, left
4:42:03coronary gives rise to LA and it
4:42:04supplies the anterior 2/3 of the
4:42:07interventricular septum. Left coronary
4:42:08also gives rise to the left circumlex
4:42:11that supplies the lateral and the
4:42:13posterior left ventricular wall. Now,
4:42:15the aorta gives rise to the right
4:42:17coronary artery and that would involve
4:42:19the inferior wall of the left ventricle.
4:42:21And then this question is asking about
4:42:23the tough case with our PDA posterior
4:42:25descending. And that's tricky because in
4:42:27right dominant individuals it's the RCA
4:42:29but in left dominant individuals it's
4:42:31the left circumlex. Okay. So the PDA is
4:42:33the weird one. And the way to think
4:42:35about this is like public display of
4:42:36affection. I just think it's right.
4:42:38You're right if you think it's right PDA
4:42:40and you're left alone if you circumvent
4:42:43the PDA. Whatever gets you there. But
4:42:45most of the time the PDA origin comes
4:42:47from the right coronary artery. Most of
4:42:48the time it's like in 85% of of people,
4:42:51but they always have to ask about the
4:42:53five or the 8% of people from which it
4:42:54comes from the left circumlex. And
4:42:56that's the left dominant heart. And
4:42:57sometimes it's co-ominant as well. So
4:42:59left dominant, you really got to watch
4:43:00out and they're going to if it's left
4:43:01dominant, it's probably going to be the
4:43:02circumlex. That's how I think about it.
4:43:04All right. And our next question, we
4:43:05have a six-year-old boy brought to the
4:43:07clinic with recurrent joint swelling and
4:43:08behavioral issue. He bites. Oh, that's
4:43:11sad. Selfmeilation. All right. So that
4:43:12immediately cues us into C. This is lean
4:43:15syndrome. You treat with alpineol and
4:43:17feic stat. That's the decreasing of the
4:43:19zanthinoxidase activity. This is one of
4:43:20the first conditions that I covered in
4:43:21my I believe it's MBME26. Question one.
4:43:24Yeah, this is like one of the saddest
4:43:25little conditions. It's intellectual
4:43:27disabilities that are seen since
4:43:28infancy. You know, the biting of the lip
4:43:30and the and the fingers. You have severe
4:43:31gout as well. Uric acid crystals,
4:43:33hematia and flank pain. It's an X linked
4:43:35inheritance pattern. You should watch
4:43:37the MBME26 recap video where I cover
4:43:39topics like this. But HGPRT is the key
4:43:41enzyme in the purine salvage pathway and
4:43:43its function to turn into GMP.
4:43:45Definitely go watch that video if you
4:43:46want a more in-depth explanation. But
4:43:48without HGPRT, you cannot salvage
4:43:50periods and then they get shunted into
4:43:52degradation and then that increases the
4:43:54uric acid and that leads to gout kidney
4:43:56stones and then the neuro symptoms. You
4:43:58treat with alipurol and fubixistat that
4:44:01blocks the zanthine oxidase to decrease
4:44:04the uric acid production. But it's leech
4:44:059 syndrome is absent HGPRT. A new a way
4:44:08you can remember this one is you know
4:44:10it's a really sad symptom that they have
4:44:11the self-biting and stuff and you could
4:44:13think that they have an absent parent
4:44:15and then I like to think of HG P RT the
4:44:19PRT kind of sounds like parent absent
4:44:23parent helps me remember that leash nan
4:44:25syndrome with the poor behavior in the
4:44:27child the neuro symptoms caused by the
4:44:29increase of that uric acid is because of
4:44:31like absent parent behavior whatever
4:44:33helps increasing uric acid intellectual
4:44:35disability self mutilation aggression
4:44:36gout and coro athtosis and that's just a
4:44:39movement disorder that's marked by a
4:44:41combination of cora with the rapid jerky
4:44:43and involuntary movements and athosis
4:44:45which involves the slow wiring and
4:44:47twisty movements. All right, so there's
4:44:49the explanation. Adenazine Damnas is
4:44:51skid oritate phosphoral transferase is
4:44:54megaloplastic anemia and responsive to
4:44:56B12. Xanthine oxidase is treated with
4:44:58alpernol carbonyl phosphate synthetase 2
4:45:01is a denovo puritamine synthesis defect.
4:45:04This is a purine salvage pathway and
4:45:05they could try to confuse you. They
4:45:06could give you glycine pathways which
4:45:09would cause encphylopathy if it were
4:45:10defective. Or they could give you serene
4:45:12problems or even zanthine oxidase.
4:45:15Zanthine oxidase converts zanthine to
4:45:17uric acid and so deficiency causes
4:45:19decreased uric acid and increased
4:45:21zanthine stones which is the opposite
4:45:23problem. There's not a deficiency in
4:45:25zanthine oxidase. It's quite the
4:45:26opposite my friend. So yep gout
4:45:28aggression retardation tonic movements
4:45:30donia. That's what you should look out
4:45:32for. Hgprt. All right. So here, this
4:45:35could be a man or a woman. So I'll go
4:45:37ahead and give you a demographic of
4:45:38both. First, we'll start with the woman
4:45:39and then we'll move over to what it
4:45:41might look like on a man. So 29-year-old
4:45:43man comes to a clinic due to recurrent
4:45:46clusters of painful blisters on the left
4:45:47side of his face. By the way, let me
4:45:49know if you'd like both of the patient
4:45:50demographics or if you just prefer the
4:45:52one relevant to the question. I think
4:45:54it's good to expand your horizons so you
4:45:56don't just lock in on one patient
4:45:57demographic for cold sores, for
4:45:58instance. But I digress. Would love to
4:46:01hear feedback. 29-year-old man. He's got
4:46:03the blisters as you can see there.
4:46:04Similar issues in college triggered by
4:46:06stress group vesicles of arithmetic base
4:46:08along the maxillary distribution. Okay,
4:46:10so it follows a distribution. What
4:46:12enabled the virus to establish the
4:46:13latency? It's retrograde axon transport.
4:46:16All right, so you might see painful
4:46:17blisters on the lips and it's recurrent
4:46:19and has like maybe a 10-year history.
4:46:21That's going to be herpes. It's HSV1
4:46:23usually. HSV2 is also possible. And they
4:46:26love this question. How does HSV get
4:46:29from the skin to the sensory ganglion
4:46:31for the latency? So the way that this
4:46:33works is HSV infects the epithelial
4:46:35cells of the mucaneous sites. So it's
4:46:38going to be the lips and the virus then
4:46:39hijacks the neuronal microtubules and it
4:46:42moves retrograde. That means backward or
4:46:44toward the cell body into the trigeminal
4:46:46ganglion for oral lesions. And there it
4:46:49establishes latency and it's basically a
4:46:51fancy way of saying you're hiding. It's
4:46:52like a game of hide-and-seek in the
4:46:54immune system. And on reactivation, HSV
4:46:56then travels anterogde anterrade which
4:46:59is forward toward the axon terminal. You
4:47:02know retrograde backward toward the cell
4:47:03body grade is toward that terminal. I'll
4:47:05say it again. Retrograde backward toward
4:47:07the body. You know like retro arcade
4:47:09games their old time. So you go backward
4:47:10toward the body the opposite way of
4:47:12where the synapse would travel and then
4:47:13they can go anterror grade afterwards
4:47:15and they go forward toward the axon
4:47:16terminal back to the skin causing the
4:47:18vesicles. That's usually what they like
4:47:20to ask about this. Now let's look at
4:47:21some of these answer choices. This is
4:47:23pretty much what I said here in the
4:47:24explanation more or less. It does also
4:47:26mention that there's movement that uses
4:47:28the dinen motor protein to move against
4:47:30the polarity toward the neuronosoma. But
4:47:32interrogate is reactivation. Exocytosis
4:47:35would be the releasing of viral
4:47:36particles, not how they move within
4:47:38neurons. Protein translation happens
4:47:39inside the affected cells.
4:47:41Neurotransmitter diffusion is
4:47:42irrelevant. HSV does not use synapses
4:47:44and neurotransmitters to spread. Some
4:47:46key terms here are action potential,
4:47:47which is electrical signaling, and
4:47:49that's not used by viruses for
4:47:50transport. protein synthesis which is
4:47:52needed to replicate the virus but it's
4:47:53not the way the latency is established
4:47:56and so maybe three questions that I
4:47:57would ask to make sure that you'd have
4:47:58this topic down pat would be one which
4:48:01process establishes the HSV latency and
4:48:04that's retrograde axon transport two
4:48:06which process reactivates it that's
4:48:08agrade axon transport and then three
4:48:10which antiviral is a guanosine analog
4:48:13that blocks viral DNA polymerase and
4:48:15that's a cycllov also valycllovir or
4:48:17famicycllovere the cyclloveres these are
4:48:19antivirals They are guanosine analoges
4:48:22that block viral DNA pymerase. And I
4:48:24actually have seen this on a test
4:48:27question before that the mechanism for
4:48:29asycllovere valycllovere and
4:48:31famicycllovere is that they are
4:48:32guanosine analoges and they are
4:48:35activated by viral thyodine kynise. They
4:48:37are phosphorolated and then you inhibit
4:48:39the viral DNA pulymerase. So there's a
4:48:41chain termination. It's using HSV12
4:48:44VZV as well. also chickenpox. It's not
4:48:47great for CMV because it's a poor
4:48:48substrate for CMV's kynise. Gan cyclloh
4:48:50is a guanocide analog for CMV. So
4:48:52gansycycllovere is a little bit better
4:48:54for cm cytogly virus and rib is a guan
4:48:56guanazine analog for RSV and HCV but
4:49:00asycllovere is activated. So think
4:49:02asycllovere associate this with with HSV
4:49:051 and two but asycllo for activated by
4:49:08viral kynise and it's used for all
4:49:10herpes. A aaa all herpes activated by
4:49:13vocal kinace HSV or VZV and VZV as well.
4:49:17Now I have to tell you one more thing
4:49:18because you're going to get tested on
4:49:20this. Asycllovere balancy famicycir
4:49:23these mechanisms are guanazine analoges.
4:49:24We talked about this. Ganzy is a
4:49:26guanazine analog that inhibits viral DNA
4:49:28pymerase. And then phoscarnate is a
4:49:30pyroofosphate analog that directly
4:49:32inhibits viral DNA. There's no
4:49:34activation required for phoscarnate.
4:49:35Sedophavir requires only a host kynise
4:49:38not the viral kynise. So just make sure
4:49:40you know the difference there. This guy
4:49:42right here is going to be seen with CMV
4:49:43reditis. That's like its use. The use
4:49:46for asycllover vycllovere and famcycll
4:49:48is going to be hsv1 and and vzv. The use
4:49:51for gan cycllovere is cmv and you can
4:49:54remember that because g kind of looks
4:49:56like a c gan cycllovere. It requires the
4:49:59viral kynise and thyodine kynise is
4:50:01required for asycllover. But phoscarnate
4:50:03does not need kynise activation and
4:50:05sudopavir requires only the host kynise.
4:50:07All right, this next question is super
4:50:08crazy easy. So, I'm not going to dwell
4:50:10on it a lot. It's just the difference
4:50:11between precision and accuracy. The
4:50:13answer is method A is more precise than
4:50:14B cuz A has less coefficient of
4:50:16variation. And B has this. And that's
4:50:18how you know it's precision. So,
4:50:19precision is another way of saying
4:50:20consistency. Look at these dots. They're
4:50:22consistently in the same spot, but
4:50:23they're not accurate cuz they're not in
4:50:24the middle. Look at this dot. It's
4:50:25accurate, but then it's maybe not
4:50:27precise cuz all the other ones are
4:50:28randomly placed. All right. So,
4:50:30precision is consistency. And the
4:50:31coefficient of variation quantifies how
4:50:33consistent measurements are relative to
4:50:35the mean. And so, the lower CV means
4:50:37greater precision. Okay. Super easy
4:50:39question and we have done the first 150.
4:50:41If you found this helpful, please like
4:50:42and subscribe. If not, just let me know
4:50:44how I can improve. I'm always happy to
4:50:45continue improving this channel. If you
4:50:47guys need tutoring from a Harvard tutor,
4:50:48just let me know. That's a good way to
4:50:50guarantee that you'll pass this exam.
4:50:51We'll see you guys in the next video.
4:50:53Hello everybody and welcome back to
4:50:54MBME29. All these questions that you're
4:50:56about to see are original. They are made
4:50:58by me. They are not copied from the
4:51:00MBME, but it's everything that I think
4:51:01you should know by the time you take
4:51:02your step one exam. So, let's dive right
4:51:04in. Question 151. A 16-year-old girl is
4:51:07referred to the endocrinologist for
4:51:08evaluation of primary amenoria. She is
4:51:11short for her age and has a broad chest
4:51:12with widely spaced nipples. This is
4:51:14Turner syndrome. She has 45X in 12 out
4:51:17of 20 metaphases and XX in the remaining
4:51:20cells which best explains the patient's
4:51:22carotype. The answer is postygotic
4:51:24mitoic non-isjunction. So you have two
4:51:26cell lines that are different which is
4:51:28mosaicism and mosaic turners arises from
4:51:31mitoic post-fertilization events. This
4:51:33is from non-disjunction early in
4:51:35embryogenesis. So some of the daughter
4:51:37cells lose an X and the others are
4:51:40normal. Here's our explanation. Myotic
4:51:42non-disjunction would be all cells
4:51:43affected. It'd be uniform across the
4:51:45board, just the X. For instance, Xlink
4:51:48deletion is the loss of a gene, not a
4:51:50whole chromosome. So it wouldn't create
4:51:51the 45X karotype. Genomic imprinting
4:51:55would have different gene expression,
4:51:56not chromosomal loss. And balance
4:51:58transllocation would not have monosomi.
4:52:01So up to 30% of Turner syndrome cases
4:52:03aren't 45x across the board. Some have
4:52:05mosaicism. So their body is made up of
4:52:08two different cell populations. So
4:52:10Turners remember there's mosaic Turners
4:52:12caused by motic error postsygotic and
4:52:14non-mosaic turners which is a myiotic
4:52:17error which is all cell lines affected.
4:52:19In our next question, a healthy
4:52:2028-year-old woman comes for
4:52:22preconception counseling. Her husband
4:52:23has a family history of autotosomal
4:52:25recess metabolic disorder that affects
4:52:27glyos degradation. His younger brother
4:52:29was affected but both parents are
4:52:31healthy. The disorder affects one out of
4:52:32every 90,000 individuals in the general
4:52:34population. The patient has no family
4:52:36history of genetic conditions and is not
4:52:38consent. Based on this information,
4:52:39what's the approximate probability that
4:52:41the patient is a carrier? So here we use
4:52:43Hardy Weineberg. Disease incidence is Q
4:52:45^2 which is equivalent to 1 over 90 K.
4:52:48That's the first step. Then we take the
4:52:50square root of both sides which gives us
4:52:511 over 300. And the carrier frequency is
4:52:542 PQ. So 2 * Q * P gives you 1 over 150.
4:52:59All right. So this is the formula you
4:53:01need to know for Hardy Weinberg
4:53:02equilibrium. That's the rare disease in
4:53:04question. So we take the square root 1
4:53:06over 300 and we get 150 as our answer.
4:53:09And the reason that we know that P is 1
4:53:11is because P plus Q is always 1 and Q is
4:53:14super super small and so P is very close
4:53:17to one. So I approximated it as one.
4:53:19That's Hardy Weenberg equilibrium. Okay.
4:53:20Here we have a 62-y old woman. Could
4:53:22also be a man. Hence the relevant
4:53:24demographic. Undergoing chemotherapy for
4:53:26breast cancer. Presents with easy
4:53:27bruising and small red spots on her
4:53:29lower legs. She denies recent trauma. On
4:53:31examination, there are numerous one to 2
4:53:34millm non-blanching arithmatic macules
4:53:36in the shins and forearms. Her gums are
4:53:37slightly bleeding during oral exam.
4:53:38Which of the following is the underlying
4:53:40cause of these symptoms? So it seems
4:53:41like she has chemotherapy induced
4:53:42thrombocyopenia. There's the photo of
4:53:44our patient. This has led to peticia. So
4:53:46the answer is going to be suppression of
4:53:48megaarioite precursors. So let's look at
4:53:50the brief explanation. Bone marrow
4:53:52suppression has led to auto body
4:53:54mediated red blood cell destruction
4:53:55would be spiricytes and jaundice.
4:53:57Inhibition of vitamin K affects the
4:53:59coagulation cascade on the platelets.
4:54:00Activation of plasminogen to plasine
4:54:02cause bleeding from multiple sites.
4:54:04That's the increased d-dimer seen in
4:54:05DIC. Congenital deficiency of factor 8
4:54:08would be hemophilia. So really tiny
4:54:10non-blanching super small pitique
4:54:12indicates that we probably have a
4:54:13primary hemostasis problem. You should
4:54:16think of low platelets whenever you see
4:54:17this or platelet dysfunction. So you
4:54:19have beta and mucinous bleeding you have
4:54:22in the gums epistaxis and that means we
4:54:24have a decreased platelet count it's
4:54:26impaired production from the meggaario
4:54:28because of all the destruction so
4:54:30primary hemostasis involves the
4:54:32platelets cause a patia perura and
4:54:35mucosal bleeding secondary hemostasis
4:54:38would be coagulation factors as deep
4:54:39tissue joint muscle bleeds and large
4:54:42echimosis so a protein C deficiency
4:54:44would be a risk for thrombosis not
4:54:46bleeding okay so here's what's happening
4:54:48We have the small red purple dots
4:54:50showing up in the skin because there are
4:54:52a lot of vessels under stress there
4:54:53because you don't have enough platelets
4:54:55and so the blood is leaking out. So
4:54:56there are not enough platelets. You can
4:54:58see this because she's getting
4:54:59chemotherapy. Chemo hurts the bone
4:55:00marrow. So you can't make the platelets.
4:55:02No platelets means bleeding. Pique.
4:55:04That's what's happening here. Here are
4:55:05the traps to avoid. Vitamin K relates
4:55:07with PT. Hemophilia would be joint
4:55:09bleeding. Red blood cell problems would
4:55:11be anemia. Too much plasma is DIC. All
4:55:14right. In this next question, a
4:55:1645-year-old man begins a new medication
4:55:17that acts as an alossteric inhibitor of
4:55:20the liver enzyme involved in fatty acid
4:55:21oxidation. Kinetic analysis with and
4:55:23without medication is a rightward shift
4:55:25on the curve. Maximum velocity remains
4:55:27unchanged. The answer is increased CM
4:55:29because this is alossteric inhibition.
4:55:31So here's alossteric inhibition. It
4:55:33alters the active site. Here are the
4:55:35differences between competitive,
4:55:36uncompetitive, non-competitive, and
4:55:38mixed. The Bmax always goes down except
4:55:40for competitive. And here the effect on
4:55:42the KM is increased and it's binding to
4:55:44the enzyme. That's competitive
4:55:45inhibition. And it's important to know
4:55:46in competitive inhibition you're binding
4:55:48to the active site. In all you're
4:55:49binding elsewhere. So here we have an
4:55:51alossteric inhibitor, not a molecule
4:55:53that's competing for that active site.
4:55:55It's all about the active site because
4:55:56competitive is reversible with the
4:55:58increased substrate and alossteric is a
4:56:00regulatory site that affects the enzyme
4:56:02confirmation. And it's the shape of the
4:56:04tur it's the shape of the curve that can
4:56:05tell you if it's competitive inhibition
4:56:07versus alossteric. So for instance, here
4:56:08would be a simple one and here is an
4:56:10alossteric one. And the way to think
4:56:12about this is in our simple one here you
4:56:14have an enzyme let's say and that makes
4:56:16this the active site and so you have a
4:56:18substrate that comes and binds right
4:56:19there. Whereas in the alossteric one we
4:56:21have an aector that binds right here and
4:56:23it causes that different looking graph.
4:56:26All right there we go. So here's the
4:56:28entire chart. So you can see alossterics
4:56:29working on different enzymes. Hyperbolic
4:56:31would be competitive. Sigmoidal is
4:56:33alossteric. Okay. In the next question,
4:56:35we have a 27-year-old woman presenting
4:56:36with acute pelvic pain and light vaginal
4:56:38spotting. She reports her last menstrual
4:56:40period was 7 weeks ago. Medical history
4:56:41is notable for prior chlamydia infection
4:56:432 years ago treated with antibiotics.
4:56:45Urine pregnancy test is positive and
4:56:46transvaginal ultrasound shows no
4:56:48intrauterine gestational sack. Serum
4:56:51beta hcg is 1,800. Which of the
4:56:54following most likely contributed to the
4:56:56patient's condition? It's a history of
4:56:58treated chlamial infection. They could
4:57:00also say it's some other ganacle or
4:57:02gorrhea infection that she had. The
4:57:04reason being chlamydia can cause tubal
4:57:06inflammation and scarring and that
4:57:07predisposes you to ectopic pregnancy.
4:57:09High beta hCG points to an ectopic
4:57:12gestation. Look at that level. So on
4:57:14step one, the big risk factors for
4:57:15ectopic pregnancy are going to be pelvic
4:57:17inflammatory disease that's most often
4:57:18caused by chlamydia or niceria. Also
4:57:21tubal surgery that can leave behind
4:57:22scarring and a previous ectopic
4:57:24pregnancy increases the risk and
4:57:25intrauterine devices and in vitro fert
4:57:28fertilization. So, it's going to be some
4:57:30previous infection, history of treated
4:57:32chlamydia infection or gorrhea. That's
4:57:34going to be the answer to the question
4:57:35like this. All right. So, there's your
4:57:37explanation here. The trap answers why
4:57:39they're wrong. Think we're going to move
4:57:40on to the next question. All right. So,
4:57:42here we have a six-year-old girl, could
4:57:43also be a young boy as well, is brought
4:57:45to the pediatrician for evaluation of
4:57:46worsening scalp tenderness. Her parents
4:57:48report that she has been more irritable
4:57:49and tired of last week. Physical exam
4:57:51shows a soft, mildly tender mass on the
4:57:54left parietal bone. T-can shows a 3 cm
4:57:56litic lesion in the parietal skull. A
4:57:58biopsy reveals numerous monuclear cells
4:58:00with nuclear grooves and infiltrate rich
4:58:03and acaphils. We have positive CD1A and
4:58:06S100. All right. So when I'm looking at
4:58:10this question, what I see is a young
4:58:12person. They have some litic skull
4:58:13lesions. They have infiltrate and then
4:58:16S100 positivity and CD1 positivity. So
4:58:19you should look out for those skolitic
4:58:21lesions, the tenderness over the oipital
4:58:23bone. And all of this should make you
4:58:25think of Lingerhan's cell hyocytosis. So
4:58:28the pathophys here is there's clonal
4:58:30proliferation of the langangerhan cells.
4:58:31These are specialized ditritic cells and
4:58:33they call them burbec granules. They're
4:58:34like tennis racket shaped. And on in the
4:58:36imuninohistochemistry will show CD1
4:58:38positivity and S100 positivity and
4:58:40langan positivity. All right. So look
4:58:42out for bone lesions also seen with the
4:58:45skin rash and it can involve the bone
4:58:47marrow of the lungs, the lymph nodes,
4:58:48the endocrine glands. So you have a
4:58:50child with litic bone lesions, a skin
4:58:51rash, recurrentitis media and a mass
4:58:53infecting the mastoid. So it's lingerhan
4:58:55cell hysteocytosis. You see burbec
4:58:57granules and CD1A S100 lingeran it's
4:59:01positive. Look for the bone lesions and
4:59:03if you see an eczema like rash, diabetes
4:59:05and cipotus, you know indicating
4:59:07posterior pituitary involvement then
4:59:08it's HSC triad. So here are the trap
4:59:11answers. Osteoid osteoma nocturnal pain
4:59:14relieved by NSAIDs in the femur and
4:59:15tibia not the skull. Wing circum is
4:59:17onion skin perostial reaction presents
4:59:20with systemic symptoms and bone cyst
4:59:22would be blood filled space on imaging
4:59:24typically multiloculated without that
4:59:27CD1A positivity and you should look out
4:59:29for those burbick granules. Now it's not
4:59:32enough to just think of bone lesions and
4:59:33you're done on step one. There are
4:59:35several conditions which can cause bone
4:59:36lesions and the one we're talking about
4:59:38is LCH which is langangeran cell
4:59:40hyocytosis and that's in children. The
4:59:42location is going to be the skull, the
4:59:44ribs and the long bones. In this
4:59:46condition, you see litic bone lesions,
4:59:47skin rash, recurrentitis media,
4:59:50diabetes, and cypitus, the ancular
4:59:51Christensen triad. And really look out
4:59:53for that CD1A positivity. Now, there's
4:59:55another condition that can cause these
4:59:57litic lesions, and that is euing saroma.
4:59:59And Euing saroma is commonly seen in
5:00:01boys that are younger than 15. They have
5:00:03long bone, litic lesions, diaphosis,
5:00:05pelvis, the ribs, and there you have
5:00:07very painful, often systemic symptoms.
5:00:10They have fever. And one thing with
5:00:12ewing is going to be an increased ESR.
5:00:14Now another litic lesion problem is
5:00:17osteocaroma. That's biodal. So elderly
5:00:20patients with page and radiation are
5:00:22going to be the demographic for osteio
5:00:24saroma. Or they could just be like 10 to
5:00:2620 but it's biodal. So not in between
5:00:30more on the extremes of the age chart
5:00:32but not right there. You'll see pain
5:00:34swelling and that has a sunburst pattern
5:00:36with a codman triangle and malignant
5:00:38osteoblasts. And the last litic lesion
5:00:41that you should know is metastasis to
5:00:42the bone that's seen in adults. And
5:00:44typically that involves the axial
5:00:45skeleton. So the spine, the pelvis, the
5:00:48ribs, the skull. And maybe you should
5:00:50also think of a solitary bone cyst as
5:00:52another option that's seen in children
5:00:53and adolescence. In the metis of the
5:00:55long bones, it's incidental and it's
5:00:58like a fluid fil cavity. It's benign.
5:01:00It's not malignant. So just to sum all
5:01:02this up, ling your hands cell
5:01:04hysteocytosis is going to be seen in
5:01:06children with skull lesions and a rash.
5:01:09It's a dendritic problem. Euing would be
5:01:11ooh they have onion skin. They also have
5:01:13that transllocation for euing as well.
5:01:15Osteocaroma has the sunburst near the
5:01:17knee and the teens. Metastasis is
5:01:20commonly seen in adults. It's a the most
5:01:22common malignant bone lesion overall.
5:01:24And then cysts are just benign. Okay. So
5:01:26those are all of the lesion associations
5:01:28you need to know for step one. All
5:01:29right. So for this one, we are
5:01:31conducting a study where we start with
5:01:33the exposure status, exposed versus
5:01:35unexposed, and then we track them over
5:01:37time and we compare the outcomes. That's
5:01:39a cohort study. And so relative risk is
5:01:41used in these studies. Odds ratio is
5:01:43used for case control and
5:01:45cross-sectional is used in a prevalence
5:01:47ratio. These three things are what you
5:01:49need to memorize. Cool. Okay. In this
5:01:51question, we have a 62-y old man
5:01:52admitted to the ICU with acute
5:01:54necroizing pancreatitis. Day three, he
5:01:56develops worsening dismia and hypoxia.
5:01:58He's intubated. Chest X-ray shows
5:01:59bilateral diffuse capacities. PAO2 to
5:02:02Fio2 ratio is 130 millimeters mercury.
5:02:06Broniovolar lavage shows no organisms.
5:02:09Lung biopsy shows avular septal
5:02:10thickening and acophilic material lining
5:02:12of the avular spaces. What describes the
5:02:14primary mechanism responsible for his
5:02:16lung findings. Okay. So this guy has
5:02:17ARDS and the answer is neutrfil induced
5:02:19injury to pulmonary epithelium and
5:02:22endothelium. It's non-cardiogenic cause
5:02:24of edema. This is acute to respiratory
5:02:26distress syndrome. And the timeline is
5:02:27interesting here because this develops
5:02:29within days after some sort of trauma or
5:02:31sepsis event. The findings are dysmia,
5:02:34hypoxmia. Hypoxmia is low oxygen in the
5:02:37blood, diffuse crackling and bilateral
5:02:39fluffy infiltrates, fluffy infiltrates
5:02:41on the chest X-ray. Now the pathology
5:02:44here is a cytoine storm in burn patients
5:02:47that causes neutrfil activation and then
5:02:48injury to the avular epithelium and that
5:02:51increases the vascular permeability
5:02:52causing proteinrich excutate to fill the
5:02:54avoli and that causes highline membrane
5:02:57formation. Okay, so the big key word to
5:02:59look for is highline highline membrane
5:03:01formation. On autopsy it'll be firm
5:03:03hyperemic lungs with widen septa and
5:03:06highline membranes. That's ARDS. It's
5:03:08not immune complex deposition that'd be
5:03:10glifitis or vasculitis. It's not type
5:03:12two pneumocy loss that's seen and
5:03:13neonatal RDS but acute respiratory
5:03:15distress syndrome involves both of them
5:03:17with neutrfil predominance type one
5:03:19hypersensitivity would be aniflaxis and
5:03:22asthma is mediated it's not relevant
5:03:24here and fibroblast would be idiopathic
5:03:26pulmonary fibrosis ards is acute not
5:03:29chronic interstial lung disease and this
5:03:31is a pretty serious condition and
5:03:32something like 40% of patients who are
5:03:34in the ICU with ARDS are not going to
5:03:37survive all right so here's the
5:03:38breakdown macrofasages release cytoines
5:03:40like TNF alpha and I1 one which summon
5:03:42neutrfils and there's that inflammation
5:03:44because of trauma sepsis or severe
5:03:46pancreatitis. The neutrfils dump enzymes
5:03:48and ROS that shred the avular epithelium
5:03:51that leads to proteinrich fluid entering
5:03:52into the avoli and those guys make the
5:03:54highline membranes that you see and the
5:03:56patient then has severe hypoxia because
5:03:58of these highline formations. The lungs
5:04:00aren't working very well and that PO2
5:04:02ratio drops Berlin's criteria for arts.
5:04:05So this is neutrfil induced injury to
5:04:06the pulmonary epithelium. All right, in
5:04:08our next question, we have a 72-year-old
5:04:10man or it also could be a woman as seen
5:04:12in this question. Has a history of
5:04:13poorly controlled hypertension, type 2
5:04:15diabetes. This is probably going to be a
5:04:16stroke, something. Yep, she has wide
5:04:18flailing movements of her left arm and
5:04:19leg. He is alerted and oriented. Could
5:04:22be male or female. Neurological exam
5:04:24reveals no cranial nerve abnormalities.
5:04:25MRI shows a small infarct in the deep
5:04:27brain structure. Which one is it? It's
5:04:28the subthalamic nucleus. Hemibblismas
5:04:31damage in the contrlateral subthalamic
5:04:34nucleus. It inhibits things through the
5:04:35indirect pathway. And so if you lose
5:04:37that inhibition then that causes
5:04:39uncontrolled movement and this is often
5:04:40due to lacunar strokes and the shedding
5:04:42of hypertension and diabetes. So here
5:04:44are the associations but the answer is
5:04:45going to be C the subthalamic nucleus.
5:04:48So you can see it right there. Now the
5:04:49associations hypertension would lead to
5:04:51lacunar strokes. So that's like the
5:04:53small vessels deep inside of your brain
5:04:55including the basil ganglia. Non-cutic
5:04:57hypoglycemia can mimic hemiolismas due
5:04:59to metabolic insult to the basil
5:05:00ganglia. Huntington's disease would have
5:05:02cora not hemibbismas and Wilson's would
5:05:04be copper deposition the basil ganglia.
5:05:06So here you have an es schemic stroke of
5:05:07the subflammic nucleus often lacunar
5:05:09thealamus becomes overactive because you
5:05:11lose that indirect pathway the
5:05:13decreasing of the inhibition and it's
5:05:15unilateral because it's just going to be
5:05:17on that one side the contrlateral limbs.
5:05:19Now there's difference between cori and
5:05:20hemibilism. Cora is involuntary regular
5:05:22purposeless flowing movements affects
5:05:24the distal limbs the face and the trunk
5:05:26continuous but unpredictable it's
5:05:27dancelike. Hemibblismas is sudden wild
5:05:30and flinging unilateral much faster.
5:05:34Coras and Huntington's and Sidenham cora
5:05:36affects the cotted nucleus whereas
5:05:38subflamic nucleus is contrlateral
5:05:39hemiblismas. All right, this next
5:05:41question is going to be really easy.
5:05:42Typically, it's going to be a young boy,
5:05:43but it could also be a female.
5:05:459-year-old girl is brought to the clinic
5:05:47because her teachers report that she
5:05:48often daydreams during class, forgets
5:05:50assignments, and seems to struggle with
5:05:51completing tasks at home. She says says
5:05:54she takes hours to finish homework
5:05:55unless supervised. no history of
5:05:56seizures, trauma, vision, and hearing
5:05:58issues. She meets developmental
5:05:59milestones and is otherwise healthy.
5:06:01They're going to give her a treatment.
5:06:02She's got ADHD. What are they going to
5:06:04give her? The answer C. Promotion of
5:06:05presinaptic dopamine and norepinephrine
5:06:07release. So, she has inattentive ADHD.
5:06:10So, you give her a stimulant and it
5:06:11increases dopamine and norepinephrine
5:06:13release in the prefrontal cortex. So,
5:06:15inattention with hyperactivity across
5:06:16settings during childhood, the first
5:06:18line stimulant would be methylenidates
5:06:20or aetamine salts. These guys have
5:06:22increasing they increase the pressaptic
5:06:24release of dopamine and norepinephrine
5:06:26and also the attention the reward
5:06:27processing is dopamine. The attention is
5:06:29norepinephrine. NMDA receptor blockade
5:06:31would be in ketamine unrelated to ADHD.
5:06:33Potentiating GABA would be benzbituates
5:06:36and that would be sedative. Serotener
5:06:38reuptake inhibition is used in
5:06:39depression anxiety and alpha 2
5:06:42antagonist would increase norepinephrine
5:06:44but not in a controlled way. They're
5:06:46adjunctive not primary therapy. So you
5:06:48can give them as part of something but
5:06:49it's not the primary therapy. And this
5:06:50is crazy because 10% of children in the
5:06:52United States are diagnosed with ADHD.
5:06:54So distractability, distractability,
5:06:56impulsivity, poor task completion as
5:06:58early as kindergarten. You give them
5:07:00stimulants, they power up the brain,
5:07:01boosting dopamine, norepinephrine just
5:07:03lets you focus. So we got a 9-year-old
5:07:05girl in attentive ADHD. Remote those
5:07:07presinaptic dopamine and norepinephrine
5:07:09release and you're good to go. Hopefully
5:07:10you guys have found this helpful. If it
5:07:11was, like and subscribe, and we'll see
5:07:12you guys in the next video. All right,
5:07:14our patient demographic could be a male
5:07:15or a female. So I'm going to include the
5:07:17female here. We're now in question 161.
5:07:19Again, all these questions are
5:07:21completely original. I've made them for
5:07:22you to prepare for step one. They're not
5:07:24copied from the MBME, but it's
5:07:25everything that you need to know by the
5:07:26time you finish your preparation for
5:07:28step one. So, here we go. 55-year-old
5:07:29woman, history of major depressive
5:07:31disorder and chronic alcohol use is
5:07:33admitted for severe nausea and fatigue.
5:07:35Lab show low sodium and she started on
5:07:38introvenous saline therapy. 3 days
5:07:39later, she becomes unable to speak and
5:07:41show profound weakness in all limbs.
5:07:42Neurological exam reveals an awaken and
5:07:44alert patient with disarthria bilateral
5:07:46babinsky signs and marked quadriplegia
5:07:48sensation and eye movements are intact.
5:07:50Which of the following structures is
5:07:51affected? The answer as you can see is
5:07:52the pawns. The reason why this is
5:07:54osmotic demilination syndrome. Here I've
5:07:56taken some notes as I've gone through
5:07:57all these questions beforehand. But the
5:07:59big thing you should know is somebody
5:08:00walks into the clinic and they've got
5:08:02super severe hyponetriia and then
5:08:04they're started on some saline therapy
5:08:060.9% saline and then later they develop
5:08:09disartharthria which is the difficult or
5:08:11unclear articulation of speech that
5:08:13otherwise is totally linguistically
5:08:14normal. Also quadripesis which is
5:08:17weakness or paralysis in all four limbs
5:08:19so arms and legs quad and the babinsky
5:08:21sign. And all these symptoms should make
5:08:23you think of a brain stem issue
5:08:25specifically in the brain stem the pawns
5:08:27and it's classic central pontine
5:08:29mileinolyis or CPM. This is also known
5:08:32as osmotic demalination syndrome ODS.
5:08:35And the pathophys is important to
5:08:37understand when you have chronic
5:08:38hyponetriia and it's corrected way too
5:08:40rapidly then water is going to shift out
5:08:42of the brain cells and that causes
5:08:44deination particularly in the pawns
5:08:46because the pawns has the cortical
5:08:48spinal and the cortical bulber tract and
5:08:51the cortical bulbar tracts. So that's
5:08:52what causes the disarthria dysphasia the
5:08:55lockedin syndrome if it's super severe.
5:08:57So this is a neurological this is a
5:08:59question in neurology about deinating
5:09:01disorder. Let's talk about what it's
5:09:03not. Internal capsule that'd be motor
5:09:05stroke that would cause hemipesis not
5:09:07quadripollegia with disarthria. Pure
5:09:08motor for internal capsule. Internal I
5:09:11just want you to link that to motor.
5:09:12Cerebellar vermis that would cause some
5:09:14trunkal atexia. Probably should move
5:09:16away from the mic to demonstrate what
5:09:18that looks like. But there you'd have
5:09:19preserved eye movement. The medulla that
5:09:21would be involved in cranial nerve 9 to
5:09:2312 dysfunction not locked in. So you
5:09:25should think respiration issues would be
5:09:27seen there. Basil ganglia would have
5:09:29movement disorders like cora and
5:09:30rigidity. All right. So there's our guy.
5:09:32There's our patient. They got the
5:09:33slurred speech, quadriplegia, binsu
5:09:36sign. That's what you should look out
5:09:37for. And I wanted to make an image that
5:09:39you guys can kind of see this in your
5:09:41mind because all these test questions
5:09:42can feel pretty abstract, but you should
5:09:44teach, you should pretend each test
5:09:46question is a new patient. And now I
5:09:48really want to break down some specifics
5:09:49here. You might have also been tempted
5:09:51to put something like mythenia gravis or
5:09:53say that this is related to the
5:09:55neuromuscular junction. It is however
5:09:57not related to the neuromuscular
5:09:58junction because disorders like myastia
5:10:00gravis do not cause upper motor neuron
5:10:02science and that's what Babinsk's reflex
5:10:04is. Plus this would have no connection
5:10:06to sodium which was our big clue. You
5:10:08might have been tempted to put gon beret
5:10:11syndrome or something like that like a
5:10:12peripheral nerve disease but that
5:10:14presents with a reflexia and ascending
5:10:16paralysis not upper motor neuron signs
5:10:18and a normal mental status. By the way
5:10:20my favorite artist Sufjan Stevens had
5:10:22gamber syndrome so look that up if
5:10:24you're curious. It's good to have an
5:10:25anchor in your mind about these things.
5:10:27So yes, this is osmotic demination
5:10:29syndrome and the actual cause is the
5:10:32rapid correction of the hyponetreia. You
5:10:35would see acute paralysis, disarthria,
5:10:37dysphasia, locked in syndrome. And the
5:10:39way that you remember this is you say
5:10:40this phrase in your head from low to
5:10:42high the pawns will die. All right? So
5:10:44put that on a t-shirt from low to high
5:10:46the pawns will die. Rapid increase of
5:10:48the sodium causes CPM. Now quick recall
5:10:50drill and by the way in the comments let
5:10:52me know if you want me to go into this
5:10:54much depth or if you prefer that I go
5:10:56quicker but just a quick recap which
5:10:58tracks are affected in central pontine
5:10:59minitis the answer is the cortical
5:11:02spinal and the cortical bulbar. The next
5:11:04recap question what is the safe rate for
5:11:06sodium correction? We mentioned this was
5:11:08too quick. So how quickly should you do
5:11:10it? Well, the answer is about 6 to 8
5:11:12mill equivalents per liter per day and
5:11:14some sources can say it's up to 10 to
5:11:1612, but lower is going to be safer for
5:11:18chronic hypo nutriia. All right. So, the
5:11:21big tip that I would give you with this
5:11:23question is anytime you see an alcoholic
5:11:25or a malnourished patient that has
5:11:26severe hyponetreia and they have
5:11:28neurologic symptoms after the sodium
5:11:30correction, then you should immediately
5:11:31be thinking of osmotic demation
5:11:33syndrome. And the first time I was going
5:11:35over this question, I drew this out for
5:11:37you guys, too. So, you can see low
5:11:38sodium. By the way, if this is helpful,
5:11:40please consider liking and subscribing.
5:11:41Videos take dozens of hours to make, and
5:11:43I'm doing it so that you have another
5:11:44way to study for step one, step two,
5:11:45step three. Let me know in the comments
5:11:47if you like the patient photo and also a
5:11:49relevant demographic photo. All right,
5:11:50let's not waste any more time. Next
5:11:52question. But basically, we got a
5:11:5345-year-old man presenting with a
5:11:54six-month history of intermittent chest
5:11:56discomfort. This could be a woman as
5:11:57well, hence my relevant demographic
5:11:58photo up there in the corner. Typically
5:12:00occurs after dinner, especially when he
5:12:02eats fried or spicy foods. He has gained
5:12:0420 pounds over the past year, and often
5:12:05lies on the couch shortly after meals.
5:12:07He denies weight loss, difficulty
5:12:08swelling, and gastrointestinal bleeding.
5:12:10He has tried over-the-c counter ant
5:12:11acids with partial relief and physical
5:12:13examination is normal. Which of the
5:12:14following mechanisms is most likely
5:12:16contributing to his symptoms? Okay, we
5:12:18have a couple of options here. We have
5:12:19to understand what's going on. So, the
5:12:21symptoms are postprandial burning chest
5:12:23pain that worsens with large or fatty
5:12:25meals. The timing, they don't really
5:12:28mention this in this question, but
5:12:29typically it's daytime and it worsens
5:12:31after you have fried foods. and ant
5:12:34acids were great, but now it's
5:12:36refractory. There's no dysphasia,
5:12:38there's no weight loss, there's no
5:12:38bleeding, and the history has maybe some
5:12:41recurrent symptoms. If this is a female,
5:12:42you might see like, you know, this
5:12:44happens whenever she's pregnant or
5:12:45something like that. And so, we should
5:12:46have a differential diagnosis list. And
5:12:48one of the top differentials should be
5:12:50gastroosophageal reflux disease. GIRD.
5:12:52You heard with PERD. Just kidding.
5:12:54That's a Parkinson quote. But this is
5:12:56GIRD. And so, the answer is going to be
5:12:57veagal stimulation causing transient
5:12:59lower esophageal sphincter relaxation.
5:13:01And the pathophys is important. The
5:13:03lower esophageal sphincter normally
5:13:05prevents acid from refluxing up. And so
5:13:07if that's too relaxed, you know, the
5:13:09vagus nerve is mediating that transient
5:13:12lower esophageal sphincter relaxation
5:13:14after meals. If it's too relaxed, then
5:13:15it allows the gastric contents to then
5:13:17enter into the esophagus. And so fatty
5:13:19foods, you know, large meals and
5:13:21chocolate, that kind of stuff, increases
5:13:23these relaxations. And repeated acid
5:13:25exposure causes mucosal irritation. And
5:13:28then that's what causes the symptoms of
5:13:30heartburn and regurgitation. All right,
5:13:32so here's the explanation. I've kind of
5:13:34said most of this already, but it's
5:13:36triggered by the veagal pathways that
5:13:38help it to relax to allow the gastric
5:13:40contents to reflux into the esophagus
5:13:42after lying down or having fatty meals.
5:13:44Why is not somatastatin induced decrease
5:13:46in bicarb? Well, that inhibits the acid,
5:13:48not bicarbonate. And so it helps not
5:13:50hurt. And it asks, what's contributing
5:13:51to this? And so is actually helping not
5:13:54contributing to that gastron
5:13:55overprouction. Pepsinogen is not the
5:13:57driver. Acid refluxes secrete mediated
5:14:00inhibition of gastric acid secretion
5:14:01that would reduce the acid alleviating
5:14:03symptoms and CCK induced gallbladder
5:14:05contraction would involve fat digestion.
5:14:08All right, so here's a relevant photo of
5:14:09the patient. Again, let me know if you
5:14:11think this is helpful and I'll start to
5:14:12include in the future. There are some
5:14:14things to know and one of those things
5:14:15is gastrin actually increases the lower
5:14:18esophageal sphincter tone and that helps
5:14:20to prevent the reflux and so it's
5:14:22protective against gird. So gastrin is
5:14:23not the right answer. Somatastatin
5:14:25inhibits gastric acid secretion and so
5:14:28that's not the answer either. Veagal
5:14:29inhibition would be wrong because veagal
5:14:31nerve stimulates esophageal paristalsis
5:14:34does not inhibit it and so gird is not
5:14:35due to the impaired esophageal
5:14:37contractions. It's due to the lower
5:14:39esophageal relaxation. So the key
5:14:42takeaway for this question is it's
5:14:44obviously a GI question about the
5:14:45esophagus and it's gird gird is the word
5:14:48gird gird gird gird gird is the word
5:14:50transient lor esophageal relaxation
5:14:52fatty foods caffeine alcohol chocolate
5:14:54large meals that kind of stuff esophagus
5:14:57could be a complication that you see
5:14:58from this esophagitis and strictcture
5:15:01and also adnocarcinoma and the treatment
5:15:03is lifestyle change proton pump
5:15:05inhibitors and anytime that you're
5:15:08taking this silly test and you see
5:15:09postprandial heartburn that is worse
5:15:11with fatty acid foods and it's good if
5:15:13you should think of the lower esophageal
5:15:15sphincter dysfunction. Now another
5:15:16question they could ask you know we
5:15:18can't cover everything but we can try to
5:15:20flesh out these topics as well as
5:15:21possible which neurotransmitter mediates
5:15:24the lower esophageal relaxation in gird
5:15:27and the answer is nitric oxide which is
5:15:30released by veagal stimulation is the
5:15:32neurotransmitter that mediates that
5:15:34lower esophageal sphincter relaxation.
5:15:36What is the most dangerous long-term
5:15:37complication of gird? Well, this is
5:15:39actually going to be via that Barretts
5:15:41esophagus pathway that I mentioned. It's
5:15:43esophageal adnocarcinoma. And
5:15:45adnocarcinoma is just a fancy way of
5:15:46saying a malignant tumor that's formed
5:15:48from the glandular structures in
5:15:51epithelial tissues. That's what
5:15:52adnocarcinoma means. All right, question
5:15:55163. Here we have a 72-year-old woman
5:15:57could be as like a young boy, an
5:15:59adolescent, as you can see here in this
5:16:01photo. Just want to make sure you're not
5:16:02super locked into this demographic. But
5:16:04they are admitted to the ICU with
5:16:05altered mental status, hypotension, and
5:16:07high fever. Her blood pressure remains
5:16:09low despite receiving aggressive IV
5:16:11fluid resuscitation. A norepinephrine
5:16:14infusion is started. The agent primarily
5:16:16acts by increasing vascular smooth
5:16:18muscle tone through stimulation of what?
5:16:19All right, let's get the lay of the
5:16:21land. If we have a patient who comes
5:16:22with shock, then we're probably going to
5:16:24want some vasoc constriction. And a
5:16:26great vasoc constrictor is the alpha 1.
5:16:27And indeed, norepinephrine in things
5:16:30like septic shock is going to target the
5:16:32alpha 1 receptor causing vasoc
5:16:34constriction. And it also causes some
5:16:37beta 1 effects as well. And by the way,
5:16:39the shock type that is best treated by
5:16:42beta 1 stimulation is cardiogenic shock.
5:16:44That's where you have the low cardic
5:16:46output. And the receptor that causes
5:16:47vasa dilation of the renal arteries at
5:16:49low dopamine doses is the D1 receptor.
5:16:52But what you should think of for this
5:16:53question is alpha 1 agonist like
5:16:55norepinephrine or highdosese dopamine
5:16:57are good for treating septic shock or
5:16:59situations where you have increased SVR.
5:17:01And so if you see vasoddilation and
5:17:03bounding pulses and warm extremities
5:17:05then you should probably be thinking of
5:17:06septic shock. Another word for this is
5:17:08distributive shock and that's where you
5:17:10have the vasoddilation. And so how do
5:17:11you treat all that vasoddilation? Alpha
5:17:131 agonism because that causes vasoc
5:17:16constriction. All right.
5:17:17Sonorepinephrine exerts its primary
5:17:19action in stimulating alpha 1's causing
5:17:21vasa constriction. This raises SVR and
5:17:24is helpful in septic shock. Dopamine 1
5:17:26that causes renal vasoddilation but it's
5:17:28used for the it's associated with the
5:17:30renal profusion. Beta 1 adinuric
5:17:32receptors increases heart rate and
5:17:34contractility. Beta 2 helps with
5:17:36broncoilation vasoddilation and alpha 2
5:17:38activation leads to decreased
5:17:40norepinephrine release lower BP and is
5:17:42harmful in shock. All right. So those
5:17:44are the explanations and this is
5:17:46important because sepsis is one of the
5:17:47top causes of death in the ICU and if
5:17:49you start them on an early visopressor
5:17:51it could save their life and the problem
5:17:53with septic shock is that the vessels
5:17:54are way too relaxed and the reason why
5:17:56is because they have cytoines like TNF
5:17:58alpha and 1 and they're causing
5:18:00widespread vasoddilation. So fluid
5:18:02resuscitation is really important but if
5:18:04it stays low if the mean arterial
5:18:07pressure still stays low like let's say
5:18:09like under 65 then it's time to
5:18:11introduce a vasopressor and
5:18:12norepinephrine is the hero drug there
5:18:14and the reason why is because of that
5:18:15alpha 1 agonism and those are GQ coupled
5:18:19receptors and they activate then phase C
5:18:21and that clamps down on the vessels to
5:18:23make them go tight. All right so there's
5:18:25the image of our patient you can see
5:18:26alter mental status he's got his IV in
5:18:29there he's undergoing septic shock. All
5:18:31right. On our next question, we have a
5:18:32seven-year-old girl running barefoot and
5:18:34her family lawn accidentally scrapes her
5:18:36foot on a sharp sprinkler head. Within
5:18:3820 minutes, her right foot becomes
5:18:40swollen, warm, and red. Physical exam
5:18:42shows localized tenderness and influent
5:18:43edema. Which of the following best
5:18:44explains the mechanism of fluid
5:18:46accumulation? All right, so we have some
5:18:47localized edema within 20 minutes.
5:18:49Within 30 minutes, what's the primary
5:18:50mechanism at play? Now you can see this
5:18:52in a lot of different scenarios but here
5:18:53we have histamine mediated endothelial
5:18:56contraction and this is due to
5:18:58reversible gap formation in the
5:18:59postcapillary venules and that gap
5:19:01allows leakage of plasma proteins and
5:19:03fluid to go into the interstitial space
5:19:05and that causes excutative edema. All
5:19:07right. So trap answers veg that would be
5:19:09involved in chronic processes and cancer
5:19:11not acute stuff but it would increase
5:19:13the permeability just not acute red for
5:19:14direct necrosis increased hydrostatic
5:19:17pressure would be heart failure or DVT
5:19:18that's a transudate not exudate and
5:19:20immune complex deposition would be a
5:19:22type three hypersensitivity which would
5:19:23be more systemic or delayed all right so
5:19:25you stub your toe get a scrape first
5:19:27responders of the mass cells releasing
5:19:29histamine that opens up the small gaps
5:19:31histamine binds and triggers
5:19:33cytokeleletal contraction making the
5:19:35wall leaky and then the fluid in the
5:19:37immune cells spill out. So you get
5:19:38warmth, redness and swelling there. It's
5:19:40the endothelial gap formation. All
5:19:42right. So there's an example of our
5:19:43little patient. Now you could also see
5:19:45this. If somebody gets stung by a bee
5:19:48for instance, then the bee venom can
5:19:50actually contain phospholipes A2 which
5:19:52disrupts the cell membrane and it
5:19:54activates arachidonic acid pathways and
5:19:56that actually triggers a mass cell
5:19:58activation. So a similar kind of
5:19:59mechanism that we were talking about and
5:20:00that mass cell deganulation causes the
5:20:03release of histamine. So now we got
5:20:05histamine and histamine causes
5:20:06vasoddilation. So that improves the
5:20:08blood flow. So if you get stung by a
5:20:10bee, you get increased blood flow. But
5:20:12you also have edema because you get
5:20:13contraction of the endothelial cells
5:20:15that causes the gaps to form the
5:20:17intercellular gaps that increases
5:20:19vascular permeability and you get fluid
5:20:21and protein leak into the interstitium.
5:20:23So that's localized swelling and edema.
5:20:25All right. So here are some buzzwords.
5:20:27Endtheal contraction, histamine,
5:20:28bradkinine, transdate versidate. Got to
5:20:30watch out for the histamines,
5:20:31lucatrines, increased permeability. And
5:20:33there's the pathophys. Some things to
5:20:35look out for, some topics that you need
5:20:36to know for step one is how to
5:20:38distinguish this from de margination.
5:20:40And that's what happens with cortisol
5:20:42with cortisol and steroids or stress and
5:20:44this does not cause edema. You should
5:20:46know fibbrin that's involved in the
5:20:48clotting not going to be involved in a
5:20:49sting. Vasoddilation increases blood
5:20:52flow and also redness and warmth but it
5:20:54does not increase vascular permeability.
5:20:56So it's not just vasoddilation. Question
5:20:58is really getting at the gap junction
5:21:00formation. So this is kind of an
5:21:02immunology inflammation question and the
5:21:05vascular changes that you see there. So
5:21:07histamine causes endothelial contraction
5:21:10that increases permeability leading to
5:21:12excutate which is proteinrich
5:21:14accumulation and it's seen in the early
5:21:16phase of inflammation. So histamine
5:21:18bradkin lucatrines CDE4 this contributes
5:21:21to endothelial cell contraction gap
5:21:23formation in the postcapular venules
5:21:25increased permeability oxidation and
5:21:27edema. So, a quick rapid recall for you
5:21:30just to make sure you got this. Which
5:21:31inflammatory mediator causes both
5:21:33vasoddilation and increased vascular
5:21:35permeability? Well, the answer is, of
5:21:37course, histamine. Yay, we learned
5:21:38something. What type of vessel is most
5:21:40affected in inflammatory fluid leakage?
5:21:41Well, that is the post capillary venial.
5:21:44And what's the difference between
5:21:45exidate and transidate? Oxidate is going
5:21:47to be proteinrich and that's due to
5:21:49inflammation because of increased
5:21:50permeability. Transidate is protein 4
5:21:53and that's because of hydrostatic
5:21:54pressure or decreased encodic pressure.
5:21:56So if they ask about localized edema
5:21:58after some sort of sting or allergy,
5:22:00then it's going to be histamine,
5:22:02endothelial gap junctions that causes
5:22:04excidation. All right, this next one is
5:22:06just kind of like an ethics principle
5:22:08here. Always apologize. Even if it's not
5:22:10your fault, apologize because they're
5:22:11feeling bad. Don't ever make any excuses
5:22:13whatsoever. Don't try to explain or say,
5:22:16"Oh my gosh, it's all Bob Jones's
5:22:18fault." Just say, "Hey, I'm sorry. My
5:22:20bad." And then say, focus on whatever
5:22:22concern they have. Don't get caught up
5:22:24in the weeds of your own ego. Just
5:22:26apologize. No excuses. All right, that's
5:22:28ethics. Next. Okay, on to our next
5:22:30practice question here. A 73-year-old
5:22:32man, could be a woman as well. Goes to
5:22:33primary care physician with fatigue and
5:22:34lightadedness when walking uphill. He
5:22:36denies chest pain, reports occasional
5:22:39near fainting spells. On exam, his
5:22:41corateed pulse is slowly rising and
5:22:42weak. Crowded oscultation reveals a
5:22:44harsh systolic murmur lattice of the
5:22:46second right intercostal space.
5:22:47Radiating toward the neck, there's no
5:22:49peripheral edema and echo cardiogram
5:22:51shows concentric left ventricular
5:22:53hypertrophy with normal ejection
5:22:54fraction. Which of the following is the
5:22:56most likely cause of his symptoms? Okay,
5:22:57so here's our guy. So you can see well
5:22:59he is an elderly patient and so the
5:23:02answer is going to be calcification of
5:23:03the aortic valve leaflets. Basically
5:23:05aortic stenosis due to calcific
5:23:07degeneration. We know this because of
5:23:09the crescendo decresendo murmur,
5:23:11corroted radiation and delayed upstroke.
5:23:12Now the symptoms you might have to look
5:23:14out for on test day are fatigue,
5:23:16lightadedness, especially if they're
5:23:17exerting and near syncopy. The exam
5:23:19would show a slow rising weak crowded
5:23:22pulse. There's also a harsh systolic
5:23:24murmur at the second right intercostal
5:23:26space and that radiates to the neck and
5:23:28you have concentric left ventricle
5:23:29hypertrophy with normal ejection
5:23:31fraction. All those signs kind of point
5:23:33toward aortic stenosis and the key
5:23:35finding really in aortic stenosis is the
5:23:37crescendo day crescendo quality and the
5:23:39second right interender costal space
5:23:40because that's the location of the
5:23:41aortic valve slow rising or weak pulse
5:23:43like pulsus parvis at tardis that's high
5:23:46for aortic stenosis as well and the
5:23:48pathophase for this is actually pretty
5:23:50simple we basically just have a stenotic
5:23:52valve and that causes resistance to
5:23:54outflow and that leads to pressure
5:23:55overload and so the left ventricle
5:23:57compensates with concentric hypertrophy
5:23:59and that preserves the ejection fraction
5:24:01at first and eventually you have
5:24:03decreased CO2 on exertion and you get
5:24:06syncopy and fatigue and anga. So this is
5:24:08kind of like a heart murmur
5:24:09cardiovascular question and the triad to
5:24:11look out for you can remember by saying
5:24:13it's sad if somebody has a stenosis
5:24:15that's because of pulmonary congestion
5:24:16as the left ventricle pressure starts to
5:24:18back up and really it's unique because
5:24:20it radiates to the corateed. All right,
5:24:22here's some trap answers. Mixatis
5:24:24degeneration of the mitro valve would
5:24:26have a click late systolic murmur seen a
5:24:28mitro valve prolapse rheumatic fusion
5:24:30opening snap diastolic rumble infected
5:24:33destruction of pulmonic valve that'd be
5:24:34a diastolic murmur with IV drug use and
5:24:36papillary muscle rupture acute mitral
5:24:39reg with hypotension and flash pulary
5:24:41edema usually postMI all right so the
5:24:43most common cause of acute stenosis in
5:24:45the elderly is calcification
5:24:47known as senile calcific
5:24:50type of murmur that increases with
5:24:51squatting and decreases with valva is
5:24:53aortic stenosis. And the difference in
5:24:55left ventricular remodeling between
5:24:56aortic stenosis and aortic regurgitation
5:24:59is that in stenosis you have concentric
5:25:01hypertrophy, pressure overload. And in
5:25:03aortic regurgitation, you get eccentric
5:25:05hypertrophy, volume overload. For the
5:25:07next question, we have a 60-year-old man
5:25:08with a history of BPH presenting to the
5:25:10emergency department with fever,
5:25:12dyseria, leftsided flank pain for 24
5:25:14hours, experienced difficulty voiding.
5:25:16Temperature 101, abdominal exam shows
5:25:18super pubic fullness and left coast
5:25:19vertebral angle tenderness. Urine
5:25:21dipstick is positive for lucasite
5:25:23estrays but negative for nitrates. Urine
5:25:25culture shows grand gram positive coxyen
5:25:27pairs and chains which the following is
5:25:28most likely. So it's grand positive and
5:25:30all the all these signs are pointing
5:25:31toward interaccus ficalis. We know this
5:25:34is like a urinary tract infection of
5:25:35some sort. We know that he has like
5:25:37pylonritis and it's like a bug
5:25:38identification question and it's
5:25:40grandpositive and so I diagnose this guy
5:25:42with acute pylonritis and the
5:25:44pathophysiology is that we have a
5:25:45grandpositive coox eye and chains. So
5:25:47our answer is C. Now here's the
5:25:49explanation but essentially this
5:25:50organism is catalas negative and it's
5:25:52part of the normal GI tract the flora
5:25:55and it can grow in bile and sodium
5:25:57chloride and it's pyr positive. Now you
5:25:59might be thinking okay well I thought
5:26:01that the most common or whatever was
5:26:02ecoli and you would indeed be right but
5:26:05that is gram positive. How about
5:26:07sheagela? You might have thought okay
5:26:08does toast shagella no because that's a
5:26:11gram negative rod and it causes bloody.
5:26:13Anytime you see shagella think blood in
5:26:15the urine and it's not piogynous not
5:26:17strep group A strep that would be
5:26:18fngitis cellulitis necroizing fasculitis
5:26:21necroizing fasciitis not a urinary
5:26:23problemsella is gram negative and the
5:26:26muccoid colon is encapsulated and
5:26:29sapiticus always think of young sexually
5:26:31active females with UTI it's rare in
5:26:32elderly men so the demographic is
5:26:34different in that one all right next we
5:26:35got a 64-y old man could also be a woman
5:26:37probably similar age undergoing
5:26:38treatment for diffuse large bell
5:26:40lymphoma his chemotherapy regimen
5:26:42includes anthro recycling agent
5:26:44initially responsible to therapy but
5:26:45then later after 6 months he has
5:26:48progressive exertional dispnia orthopia
5:26:50and bilateral lower extremity edema
5:26:52physical exam shows by basler crackles
5:26:54JVD and third heart sound echo
5:26:56cardiogram reveals dilated left
5:26:57ventricle and ejection fraction of 30%
5:26:59what describes the mechanism all right
5:27:00so there's a new patient that fits this
5:27:02question's demographic and the answer is
5:27:04going to be oxidative injury from free
5:27:05radicals and we said anthror but maybe
5:27:08it would have helped if you missed this
5:27:10question to know doxy rubicon which is
5:27:12an anthroyc it's ly used and that
5:27:13develops cardiomyopathy and the
5:27:15mechanism of toxicity is what you need
5:27:16to know. So doxy rubicon any of like the
5:27:18rubicons will intercolate the DNA and
5:27:21inhibit toposomeas 2 but the
5:27:24cardiotoxicity will be caused by iron
5:27:26dependent generation of free radicals
5:27:28and that leads to lipid proxidation of
5:27:30the cardiammyio and so you get myioy
5:27:32necrosis and dilated cardiammyopathy. So
5:27:34the cardiammyopathy is dose dependent
5:27:36and the causes of dilated
5:27:37cardiammyopathy in this question is
5:27:39clearly from that anthroyc from the doxy
5:27:41rubeson. So hisystologically you have
5:27:43myophibbral losses, vaccization which is
5:27:45the formation of vacules, the small
5:27:47membrane bound sacks within the cells
5:27:49and those can be a sign of cellular
5:27:50stress and also interstatial fibrosis
5:27:52you might see. So really a way to
5:27:54simplify this question it's just a just
5:27:55a nice little easy farm question and
5:27:57you're giving them some sort of like an
5:27:58anti-tumor antibiotic you know doxy
5:28:00rubicon and that causes dilated
5:28:02cardiammyopathy which is a dose limiting
5:28:04toxicity. You have free radical induced
5:28:06damage to the myioytes. And so you could
5:28:08give them something like that's an iron
5:28:11chilator that prevents cardiotoxicity.
5:28:12Okay. Some trap answers why they're
5:28:13wrong. Beta amalloid would be
5:28:15restrictive cardiammyopathy and
5:28:16amalidosis. Calcium phosphate distrophic
5:28:19calcification. Immune complexes would be
5:28:21lupus myocarditis. So Dr. Ruben enters
5:28:23the cardiac cells goes through redux
5:28:25cycling turns out reactive oxygenating
5:28:27species. They punch holes in the heart
5:28:29muscle cells causing apoptosis and
5:28:30dilated cardiammyopathy. That's what we
5:28:32give them to protect. All right. And now
5:28:34some of you guys might be wondering
5:28:34about EGFRs. So EGFR inhibitors
5:28:38lextoximab are actually going to cause a
5:28:40papular postular rash non-c
5:28:42cardiammyopathy. Papular postular just
5:28:44means you have the papules which are the
5:28:45small little raised bumps and the
5:28:47pastules which are pus filled. So you
5:28:49get that redness, the flushing of the
5:28:50skin, the raised bumps with pus and
5:28:52that's related to blood vessel dilation,
5:28:54bacterial overgrowth, that kind of
5:28:56stuff. It's not the abnormal myoglobin
5:28:58because myoglobin release. Anytime you
5:29:00think of myoglobin release, you should
5:29:01think of rabdomiolysis,
5:29:03not chemotherapy induction. And vincine
5:29:05would cause impairment of actin
5:29:07synthesis. That's Vin Christine's job.
5:29:09All right. In our next question, we have
5:29:11a 2-year-old male neonates born at 39
5:29:13weeks gation, noted for severe
5:29:14respiratory distress after birth.
5:29:16Physical exam shows nasal flaring,
5:29:18grunting, subcostal retractions, abdomen
5:29:19is scaffoid. Breath sounds are
5:29:21diminished on the right. Heart sounds
5:29:23more prominent on the left. Chest X-ray
5:29:24shows bowel loops occupying the right
5:29:25thoracic cavity with leftward medicinal
5:29:27shift. Which of the following structures
5:29:29most likely failed to develop properly?
5:29:30And our answer is C. The right pluro
5:29:33peritineal membrane. I see this more as
5:29:34a memorization question, but typically
5:29:36you have like a full-term newborn. They
5:29:38got respiratory distress and they have
5:29:40abdominal contents in the thorax
5:29:42somewhere. It's a congenital
5:29:43diaphragmatic hernia. Then you just have
5:29:45to memorize that congenital
5:29:47diaphragmatic hernia is due to that
5:29:49failure to fuse the right plur the
5:29:51pluroparitinal membrane with the septum
5:29:53transversum. That's what causes the
5:29:55hernia. It's that failure to fuse. And
5:29:56the thorax by the way is the part of the
5:29:58body on any mammal that's between the
5:29:59neck and the abdomen. And so it's
5:30:01usually referring to like the cavity
5:30:02that's enclosed by the ribs. It's like
5:30:03that that breast bone area that dorsal
5:30:05vertebrae. Usually it has the chief
5:30:07organs of circulation and respiration.
5:30:09So what happens in this little baby is
5:30:11that you have the compression of those
5:30:13developing lungs and pulmonary
5:30:15hypoplasia and respiratory failure. And
5:30:17so this is often associated with
5:30:18persistent pulmonary hypertension of the
5:30:20newborn. Think of this as an embryology
5:30:22question and diaphragm development
5:30:24question. It's a congenital
5:30:25diaphragmatic hernia because of the
5:30:27defective development of the
5:30:28pluroparitinal membrane and that leads
5:30:29to pulmonary hypoplasia and it's usually
5:30:32leftsided and that's the reason being
5:30:34that the liver protects the right side.
5:30:35Okay, here the trap answers whether
5:30:36wrong. Septum transversum is rarely the
5:30:38sole defect here. Pulmonary endoderm
5:30:41affects lung tissue development. Plurop
5:30:42paricaricardial fold separates the
5:30:44paricardium and the plural cavity.
5:30:45Cervical somites provide the muscle. So
5:30:47the diaphragm is kind of like a little
5:30:49quilt. It's made of pluroparitinal
5:30:51membrane. Transverse and somites. What
5:30:52happens here is that the abdominal
5:30:53organs slip through the hole into the
5:30:56thorax pulmonary hypoplasia. Now you
5:30:58can't breathe. Now the abdomen's sunken
5:31:00because the bowel is not in the belly.
5:31:01It's in the chest. Wild. Now some other
5:31:03answers you could see would be like the
5:31:04diaphragmatic cruise and that gives
5:31:06support but it's not the side of the
5:31:07herniation and septum transversum is
5:31:10what actually forms the central tendon
5:31:12that's possible but it would form the
5:31:13rare central hernia not CD8. All right.
5:31:16Now, look at this absolutely adorable
5:31:17infant. 3-month old male, could be
5:31:19female, as you can see here, born at
5:31:21term, 9 lb, has an enlarged tongue,
5:31:24prominent umbilical hernia, asymmetry of
5:31:26the limbs in the right leg appearing
5:31:27longer than the left. Abdominal
5:31:28ultrasound shows heterogeneous mass of
5:31:30the right kidney. Genetic analysis
5:31:31demonstrates loss of maternal
5:31:32methylation through imprinting on 11:15.
5:31:34Which of the following best explains the
5:31:36pathogenesis of this patient's
5:31:37condition? Okay, so there's a little
5:31:38little baby that represents this
5:31:40demographic in this question. Super
5:31:42cute. Pediatrics is the absolute best,
5:31:43by the way. Now this is a condition
5:31:44known as Beck with Widman syndrome. And
5:31:47a couple of things are seen here. One is
5:31:48excessive birth weight and maybe some
5:31:50post-nasal overgrowth. They typically
5:31:52have a large tongue macro glossia.
5:31:54That's super classic for BWS. They could
5:31:57also have that stork bite, but that
5:31:58could be kind of non-specific. And one
5:32:00thing to really look out for that's
5:32:01super high yield that they're going to
5:32:02test you on is the abnormal mass Wilms
5:32:05tumor. That's a high yield for BWS. And
5:32:07there's a genetic mutation of 11 p15.
5:32:10It's the abnormal methylation which is a
5:32:12huge clue as well. And the path of fizz
5:32:15here is that there's a loss of
5:32:16imprinting or uniparental daisome of
5:32:19that 11p5. And so that affects the
5:32:22insulin like growth factor 2 which is
5:32:24the paternally expressed growth promoter
5:32:26or could affect the maternally expressed
5:32:27growth suppressor. And so normally one
5:32:30parental al is active, right? We're
5:32:32familiar with imprinting there. But in
5:32:33BWS both alals are expressed and so
5:32:36there's overgrowth. So you're expressing
5:32:37IGF-2 which is the paternally expressed
5:32:40growth promoter and you're also
5:32:42expressing the maternally expressed
5:32:43growth expressor and imprinting is the
5:32:45epigenetic silencing of only one
5:32:48parental alil and it's mediated by DNA
5:32:50methylation and histam modification. An
5:32:52example of that is Prader Willy starts
5:32:53with a P and so which one's deleted? The
5:32:55P. Angel man, what success to you is the
5:32:57man in that. So it's maternal deletion.
5:32:59And Beck with Weidman is a bilelic
5:33:02paternal like expression. It's not
5:33:03heteroplasm, that's mitochondrial DNA
5:33:06variation. It's not anticipation, that's
5:33:08like Huntington's disease or monic
5:33:10distrophe. It's not plyotropy, that's
5:33:12one gene. So plyotropy is one gene that
5:33:14affects many other systems. An example
5:33:16of that is PKU. And the most common
5:33:19tumor seen with Beckwith is Wilm's
5:33:20tumor. So look out for the nephrolasts
5:33:24and the gene that's normally maternally
5:33:25imprinted and overexpresses IGF-2. So
5:33:27it's abnormal imprinting is the loss of
5:33:29methylation on the maternal alil and
5:33:31that causes biic expression and so the
5:33:33answer is epigenetic silence failure.
5:33:35All right. So it's not Huntingtons or
5:33:36fragile X, that'd be triplets.
5:33:38Mitochondrial heteroplasm. Variable
5:33:40expression chromosomeal non-disjunction.
5:33:42That's like downs and germ line would be
5:33:44multiple affected siblings but normal
5:33:46parents. All right, here are the
5:33:47buzzwords. Microsomia, IGF-2
5:33:50overexpression, neisleas, poor widest
5:33:53stain common in syndromes involving
5:33:54overgrowth and vascular malf formations
5:33:56in Wilms, renal malignancy, macrosia,
5:33:59big tongue, abnormal methylation, defect
5:34:01of the maternal. And so the maternal
5:34:03suppressor normally silences through
5:34:05methylation, but in BWS, the maternal
5:34:07methylation's lost, and so you can't
5:34:09suppress that gene, so you just get
5:34:11dad's growth factor. Mom was supposed to
5:34:12press the mute button. She didn't, and
5:34:14now the baby is playing twice as loud. I
5:34:15like that. Guys, thank you so much for
5:34:17watching these 10 questions. Well,
5:34:18everybody, welcome back. Here are 10
5:34:20more questions that are going to help
5:34:20you pass step one. In our first
5:34:22question, a double blind randomized
5:34:24clinical trial investigates the effect
5:34:26of novel therapy in patients with acute
5:34:28mioardial inffection. Patients are
5:34:30randomized to receive either the
5:34:31experimental therapy or a placebo within
5:34:336 hours. The relative risk of the
5:34:35recurrent MI in the treatment group is
5:34:3765 and the confidence interval is 04
5:34:41to.9. Relative risk of all cause
5:34:43mortality is82 and the 95% confidence
5:34:46window is
5:34:4859 to 1.12. Now the question is which of
5:34:51the following best summarizes the
5:34:53findings for the treatment group
5:34:54compared to the placebo and the answer
5:34:56is significantly lower risk of MI
5:34:58recurrence but no significant difference
5:35:00in mortality. All right. So what is
5:35:02first of all relative risk? We need to
5:35:03know that is the likelihood of an
5:35:05outcome like death, disability,
5:35:07mioardial inffection between the
5:35:09treatment group and the control group,
5:35:11those who get the placebo. And the
5:35:12formula is literally just the risk of
5:35:14the treated over the control. And if the
5:35:16relative risk equals one, that means
5:35:18there's no difference. If relative risk
5:35:19is greater than one, then the treatment
5:35:21increases the risk. Like let's say it's
5:35:23two, that means it's bad. And if the
5:35:25relative risk is less than one, then the
5:35:26treatment reduces the risk, which is
5:35:28good. But there's also this thing called
5:35:29a confidence interval. Typically, we use
5:35:31a 95% confidence interval. And that
5:35:33tells you if we repeated this study 100
5:35:35times, the true relative risk would fall
5:35:38within the range 95 times. And so, for
5:35:40the relative risk to be statistically
5:35:42significant, the entire 95% confidence
5:35:44interval has to be above or has to be
5:35:48below one because if it includes one,
5:35:50then it could go up or down and it
5:35:52wouldn't be statistically significant.
5:35:53And that's why in this question, there's
5:35:54no significant difference in mortality
5:35:56in this group because the confidence
5:35:57interval includes one. You don't know if
5:35:59it's gone up or down. It's not
5:36:01statistically significant. That's all
5:36:02you need to know for this first
5:36:03question. In this next question, a
5:36:0572-year-old woman, it could be a man.
5:36:07That man could look like this, but for
5:36:09our purposes, it's a 72-year-old woman
5:36:11with congestive heart failure that
5:36:12started on a new diuretic to manage
5:36:14volume overload. After 5 days, she
5:36:16presents with new onset fatigue and
5:36:18lightheadedness. Her labs show sodium
5:36:20134, potassium 2.8, bicarb 33, chloride
5:36:2392, pH 7.48. What describes the acid
5:36:27base and volume status in this patient?
5:36:29All right, so looking at that pH, we
5:36:30know that it's going to be alkalossis.
5:36:32So we can cross off the acidosis. I've
5:36:34gone ahead and updated the patient
5:36:35demographic for this question. And the
5:36:37reason why is because loop diuretics can
5:36:39cause the loss of sodium and the loss of
5:36:41potassium and chloride that results in
5:36:43volume contraction. And so the answer is
5:36:45alkalossis volume contraction. The
5:36:47volume contraction then activates the
5:36:49renin aldostrone angotensin system. So
5:36:51now if aldostrone is active, it'll
5:36:53promote hydrronium ion and potassium
5:36:55loss. that leads to metabolic
5:36:56alkalossis. And so the mechanism that
5:36:58you have to know is that loop diuretics
5:37:01activate the RAS system that leads to
5:37:03increased hydrronium and potassium loss
5:37:07in the urine and that leaves behind a
5:37:09relative excess of bicarbonate. And
5:37:11specifically how this works is a loop
5:37:13diuretics cause volume loss. They block
5:37:15the sodium potassium the sodium
5:37:18potassium chloride reabsorption in the
5:37:20thick ascending limb. And the loss of
5:37:22sodium means you have less water
5:37:23reabsorption, right? because water
5:37:25follows sodium and so you have less
5:37:26water reabsorption and that means volume
5:37:28contraction. Now volume contraction
5:37:30means RAS activation which is the renin
5:37:32angioensin 2 aldoststerone system and so
5:37:35eldoststerone what does that do it
5:37:36increases the sodium reabsorption at the
5:37:39expense of potassium and hydrronium
5:37:42hydrronium secretion and that's in the
5:37:44collecting duct. So hydrronium loss
5:37:45leads to alkalossis obviously right
5:37:47there's less acid in the blood that's
5:37:48alkyossis and that happens through the
5:37:50type A and circulated cells in the
5:37:51collecting duct where the hydrononeium
5:37:53ions are exchanged for sodium via
5:37:55aldoststerone. So eldoststerone goes and
5:37:56it's like hey let's exchange
5:37:57hydrononeium ions for that sodium. Maybe
5:37:59a good way to think about contraction
5:38:01volume contraction is like imagine this
5:38:03right here is a nice warm bowl of soup.
5:38:06Yummy. That's a nice soup. And if you
5:38:08boil it down or imagine it's just full
5:38:09of water. If you boil this down that's
5:38:11volume contraction. Then the
5:38:13concentration of bicarbonate increases
5:38:15even if you don't add any more base.
5:38:18That's contraction alkyossis. There's a
5:38:20relative excess of bicarbonate due to
5:38:22the fluid loss. So this is a classic
5:38:25renal question on diuretics acidbased
5:38:27disturbances. So loops lose volume lose
5:38:30hydrronium ions and that causes
5:38:32alkyossis because of that relative
5:38:34increase in the bicarbonate. Next we
5:38:35have a 36-year-old man has to be a man
5:38:37presents with two-month history of dull
5:38:39scruttal heaviness and swelling on the
5:38:41left side. He works at a warehouse and
5:38:42notices the mass worsens by the end of
5:38:44the shift. He denies pain, fever, trauma
5:38:46or urinary symptoms. Physical exam
5:38:48reveals soft irregular mass superior to
5:38:50the left testes that enlarges with valva
5:38:52and does not translluminate. His creatin
5:38:54is 2.6. Urine analysis shows mild
5:38:57proteinura. What best explains these
5:38:59scrotal findings? All right, so we got a
5:39:00dude could be a little older. This guy's
5:39:02a little younger. They might have
5:39:04several conditions. They might say
5:39:05you've got diabetes, you got
5:39:06hypertension, but we do note that the
5:39:08creatinin is 2.6. That is elevated. So
5:39:10that means he has chronic kidney
5:39:11disease. All right. So now maybe they
5:39:13also say that he has some sort of
5:39:15perorbital or lower extremity edema. You
5:39:17might have some unilateral left. Usually
5:39:19they'll say scrotal swelling and there's
5:39:21a mass just superior to the testicle.
5:39:23And they'll say that it enlarges with
5:39:25valva. So this is our classic varicoseal
5:39:27due to renal vein hypertension. And this
5:39:29is like when the p the patient bears
5:39:31down like the valva maneuver then the
5:39:33venus pressure increases and the veins
5:39:35that are already dilated become more
5:39:36prominent. And a varicose seal is the
5:39:38dilated veins in the panenopform plexus.
5:39:42And so increased pressure makes the vals
5:39:44makes the veins swell even more. And
5:39:46that causes the mass to get larger when
5:39:47you're standing or during bala maneuver.
5:39:49And that's why they have to say the mass
5:39:51enlarges when they're standing or doing
5:39:52balva or they're decompressing when
5:39:54supine something like that. A hydra seal
5:39:56can slightly enlarge. Cancer would have
5:39:58no change. Torsion would have acute
5:40:00pain. Epigitis would be painful. And a
5:40:02cyst would not change as well. Here's a
5:40:05brief explanation. leftsided because the
5:40:06left drains the left gonatal there's an
5:40:08obstruction compression elevates venus
5:40:10pressure in the barrical and then also
5:40:11diabetes history leads one to think of
5:40:13the kidney disease kidney damage
5:40:15contributing to venus hypertension
5:40:17abdomio saroma would be painless
5:40:18testicular torsion would be sudden
5:40:20severe high writing testes inguinal mass
5:40:22extension may translinate as well and
5:40:25the epidmal cyst would be painless round
5:40:27fluid fil mass that transluminates and
5:40:29does not enlarge with valva this is
5:40:31pretty common 50% of men have it don't
5:40:33know it and it's because the left vein
5:40:34drains into the left renal vein which is
5:40:36then sandwiched between the aorta and
5:40:37the superior mesenteric artery. So when
5:40:39pressures rise you think the left side
5:40:40look for the bag of worms that doesn't
5:40:42trans elilluminate. Answer is varicosil.
5:40:44All right for this next question step
5:40:46one loves to ask you about vitamins A,
5:40:48D, E and K. Bill biliaryia you need to
5:40:52know is the absence or obstruction of
5:40:54the extra hypatic bile ducts that leads
5:40:56to cholestasis means the bile cannot
5:40:59reach the intestine. You know literally
5:41:00this means the stasis of that bile. No
5:41:03bile means that you cannot form your my
5:41:04cells and so you have decreased fat
5:41:06absorption induced vitamin deficiencies
5:41:08and vitamin E is one that causes
5:41:10neurologic problems and who a little
5:41:12baby as you can see here look at that
5:41:14little baby so cute and so you see
5:41:16jaundice pale stools dark urine
5:41:18hyperbilly rubmia and these deficiencies
5:41:21if untreated it can cause cerosis and
5:41:23liver failure so in our question we have
5:41:25the photo here it is a 6- week old girl
5:41:28brought to the pediatrician for
5:41:29persistent jaundice her mother notes
5:41:31that her stools have become increasingly
5:41:33pale and urine appears dark. On exam,
5:41:35the infant has hpatomegaly and scleral
5:41:37ictus. Lab studies showed direct
5:41:39elevated direct Billy Rubin and alkaline
5:41:41phosphotase. Hyus scan reveals failure
5:41:44of the radioracer to reach the dadum.
5:41:46The patient underos surgical
5:41:47intervention to restore bile flow. She
5:41:49is at risk of developing a deficiency in
5:41:51which of the following nutrients? Answer
5:41:52ad vitamin E. So look out for the
5:41:55jaundice, the pale stools, congenital
5:41:57billy billiaratriia is the diagnosis
5:42:00usually here. Biliary atreasia means
5:42:02there's no bile. No bile means there's
5:42:04no fat absorption at least deficient
5:42:06absorption because bile is needed to
5:42:08emulsify the fats. Right? So if you
5:42:10don't have the bile then the fats can't
5:42:12be absorbed and you get stattera and
5:42:14stattera is just the presence of a lot
5:42:15of fat in the stools and so they're
5:42:17going to be oily and bulky and foul
5:42:19smelling. Everything else is going to be
5:42:20water soluble like B6 B12. Here's the
5:42:23brief explanation. You might see for
5:42:25instance spinal cerebral degeneration
5:42:27and hemolytic anemia in infants. Not
5:42:29asorbic acid that's water soluble. These
5:42:31are all going to be water soluble.
5:42:32Nyasin, thamine, ribboflavin, and
5:42:34ascorbic acid. All right. Fat deficiency
5:42:36because there's no bile. That's the way
5:42:37to think about this question. You will
5:42:39100% see ADK on your test. No doubt. All
5:42:42right. In our next question, it could be
5:42:44a male or a female, but I'm putting the
5:42:46female demographic cuz I feel like it's
5:42:49going to be more common that way. A
5:42:5068-year-old man presents with fatigue,
5:42:52diffused bone pain, and difficulty
5:42:53climbing stairs over the past year. He
5:42:55has a history of alcohol use disorder
5:42:56and recently was treated for chronic
5:42:58pancreatitis. Physical exam shows
5:43:00tenderness of the ribs and thighs.
5:43:02Calcium is low, phosphate is low, ALP is
5:43:05high, PTH is high, 25 is super low. What
5:43:08explains these symptoms? The answer is
5:43:10going to be, well, first, why don't you
5:43:12decide, and I'll give you some potential
5:43:14clues here. There's diffused muscle
5:43:16pain, maybe some proximal weakness for a
5:43:17long time, typically like 6 months or
5:43:19so. And the pain worsens with activity.
5:43:21There's a tender shin surface. You got,
5:43:24you know, bone pain essentially is what
5:43:25that means. There's proximal muscle
5:43:27weakness, metabolic myopathy. If it's a
5:43:30female, then they could have or maybe
5:43:32another clue would be lack of sunlight
5:43:34exposure. They have decreased calcium,
5:43:36increased parathyroid hormone. And if
5:43:37it's decreased calcium, that means a
5:43:38secondary hyperarathyroidism. And so in
5:43:41adults, if you're noting defective
5:43:43mineralization, then it could be due to
5:43:45several things. One of them is going to
5:43:46be vitamin D deficiency. It could also
5:43:48be a calcium deficiency and also it
5:43:50could be a phosphate deficiency. And if
5:43:53that happens, the bones are going to
5:43:54become soft and weak and painful. So if
5:43:56you have low calcium and high PTH that's
5:43:58secondary hyperarathyroidism and the
5:44:00most common cause in the elderly for
5:44:02instance here's an elderly man could be
5:44:04an elderly woman most commonly causes
5:44:06vitamin D deficiency so the answer is
5:44:07osteomacia it's the adult equivalent of
5:44:09ricketetts all right pet's disease of
5:44:12bone mosaic laminer bone is wrong
5:44:14because the alp is elevated but these
5:44:16guys are normal in vette the bone pain
5:44:19is localized non- diffuse vitamin D
5:44:21resistant ricketetts would be in
5:44:22children's multiple myoma litic lesions
5:44:25hyper for calcia. That's wrong because
5:44:26of the low calcium and the lack of the
5:44:28renal dysfunction, the M spike and the
5:44:30anemia. Primary hyperarathyroidism,
5:44:32classic stones, bones, groans,
5:44:34psychiatric overtones. They have that
5:44:36would cause hypercalcemia. This is
5:44:37hypocalcemia. All right, there is the
5:44:39mechanism. Now, it's not
5:44:41hypoparathyroidism because that would
5:44:43show low PTH and low calcium. But here
5:44:45we have high PTH. It's working. We just
5:44:47can't do anything because of that
5:44:49vitamin D deficiency. So, we can't get
5:44:50enough calcium. That's why we're
5:44:51increasing the PTH. It's not metastatic
5:44:53breast cancer that causes hypercalcemia,
5:44:56not hypocalcemia. It's not primary
5:44:58because primary would have increased
5:45:00calcium and increased parathyroid
5:45:01hormone. And it's not osteoporosis
5:45:03because that will usually show normal
5:45:05labs. It's usually asymptomatic until
5:45:07they have some sort of a fracture. So
5:45:08vitamin D deficiency means you have
5:45:10defective mineralization of the osteoid.
5:45:12Low vitamin D means low calcium and
5:45:13phosphate triggering compensatory PTH
5:45:15which worsens phosphate loss and tries
5:45:17to maintain calcium by breaking down the
5:45:19bone. But without enough vitamin D, the
5:45:21bones cannot mineralize well enough,
5:45:22leading to pain, fractures, and muscle
5:45:23weakness. Now, vitamin D does not create
5:45:25calcium. It does help your body absorb
5:45:27it from the gut. So without it, you eat
5:45:29the calcium, but it passes right through
5:45:31with vitamin D and induces expression of
5:45:33the calcium binding proteins. And if
5:45:34you're deficient, you can't absorb the
5:45:35calcium at all. Right? Your blood
5:45:37calcium will drop in the parathyroid
5:45:38glands are going to freak out and be
5:45:40like, "Oh my gosh, secondary
5:45:41hyperyroidism time. Let's try to save
5:45:44this patient." All right? And that's
5:45:45that question. In this next question, we
5:45:46have a 43-year-old woman brought to the
5:45:48emergency department after being found
5:45:50unconscious in her apartment. On exam,
5:45:51she's hypotensive and unresponsive.
5:45:54Okay, this could be a man as well. T
5:45:56shows a large adrenal hemorrhage after
5:45:58stabilization. Her serum cortisol is
5:46:00undetectable. Okay, so here's our
5:46:01patient demographic for this question.
5:46:04ACT is remarkably elevated, marketkedly
5:46:06elevated. Which of the following cells
5:46:08is most likely responsible for increased
5:46:10hormone and driving cortisol? All right.
5:46:13So, everybody knows that the answer here
5:46:15has something to do with ACT. We know
5:46:17that. Now, what we don't know and what's
5:46:19hard to learn is that the anterior
5:46:21pituitary is where the CR stimulates ACT
5:46:25adrenocropic hormone and ACT is secreted
5:46:28by the basoils specifically the
5:46:30corticotroes and it's derived from palm
5:46:32C and you will see this in the MBMES and
5:46:34the adrenal cortex the zonopiculata is
5:46:36where ACT stimulates the cortisol
5:46:38production. So, to answer this question
5:46:40we have to know a couple of things. We
5:46:42got to know basophils in the anterior
5:46:43pituitary include corticotroes,
5:46:46thyrorroes and gonadotroes. So cortico
5:46:48would be like act. Thyotroes would be
5:46:50like TSH. Gonatroes would be LH and FSH.
5:46:53That's the anterior pituitary. You can
5:46:54think of it like the base that you build
5:46:56off of. So basoils. You can also think
5:46:58of B flat, right? B flat because FSH,
5:47:02LH, ACT, TSH, B flat. And so our answer
5:47:05is basil of the anterior pituitary
5:47:07because the ACT is elevated and that is
5:47:09because of the corticotroof stimulation.
5:47:11So primary adrenal insufficiency due to
5:47:13the unreal this leads to unregulated ACT
5:47:16secretion from the pituitary basoils.
5:47:18Follicular of the thyroid makes thyroid
5:47:20hormone in response to TSH. Chromophin
5:47:22cells releases epinephrine
5:47:23norepinephrine. Parvosellular neuron of
5:47:25the hypothalamus produces CR. It's
5:47:27upstream but it's not the source of ACT.
5:47:30Acetaphil of the anterior pituitary
5:47:32makes the growth hormones not B flat. So
5:47:34as I mentioned before, ACT comes from
5:47:36the adrenadulla. It's produced in the
5:47:38anterior pituitary by the basopils,
5:47:40specifically the corticotroes. They
5:47:42respond to CR. They cleave the palm C
5:47:44into ACT, MSH, and betaendorphine. Now
5:47:47just to be super clear, the accetoils,
5:47:49those stain, you should think of
5:47:51prolactin and growth hormone. And the
5:47:52way to remember those would be pig.
5:47:54Prolactin growth hormone. Think of a
5:47:56really toxic, a really acidic pig.
5:47:57Basopils, you remember B flat, FSH, LH,
5:48:00ACT,
5:48:02TSH. All right, just to do a quick quiz
5:48:04for you. What's growth hormone?
5:48:05Acetaphil. What's TSH? Basopil. What's
5:48:08prolactin? Acettoil. ACT LH basopils.
5:48:12You got it. All right. In our next
5:48:14question, we have a 55-year-old man, but
5:48:16could also be a female, as denoted in my
5:48:18demographic photo right here. So, this
5:48:20man presents with acute shortness of
5:48:22breath and puritic chest pain while
5:48:23climbing stairs. He returned from a
5:48:2510-hour flight. DVT is now in our minds.
5:48:27History of hypertension. Wow. Yep.
5:48:29Typnic oxygen sat of 88 X-ray normal
5:48:33ventilation profusion scan reveals
5:48:35profusion defect to the right lower lobe
5:48:36which vessel provides collateral
5:48:37oxygenation oxygenated blood to the lung
5:48:40parankma. All right, I've updated the
5:48:42patient demographic so you can see what
5:48:43this guy looks like. That's how he
5:48:45presents. Now, what is the answer? Okay,
5:48:47so they can present this a couple of
5:48:48ways. They'll say this person has a lot
5:48:50of chest pain, you know, the cough,
5:48:52they're smoker. If it's a maybe they'll
5:48:55say it's a female taking oral
5:48:56contraceptives. That's like an increased
5:48:58emolic risk. You might see some sinus
5:49:00teacardia on the ECG and a pulmonary
5:49:03embolism. What's interesting about that
5:49:04is that you actually have a normal chest
5:49:06X-ray. And this scan is going to show a
5:49:09profusion defect in the right upper
5:49:11lobe. And now that's all well and good.
5:49:14We know it's a pulmonary ambism. Easy.
5:49:16But they're asking which artery provides
5:49:17collateral blood flow to that spot. So
5:49:19you have to know the blood supply of the
5:49:20lungs. I think it's worth talking about
5:49:23the lungs for a sec and pulmonary
5:49:25circulation generally. So here's our
5:49:27heart. This originates from the right
5:49:28ventricle to the pulmonary trunk and
5:49:30then it divides into the right and the
5:49:31left pulmonary arteries and that
5:49:33delivers de oxygenated blood to the
5:49:35lungs for gas exchange. But there's also
5:49:37this thing right cuz that's that's the
5:49:39pulmonic circulation. It's pretty low
5:49:40pressure. It originates from the right
5:49:42ventricle. There's also this other type
5:49:43and it's bronchial circulation. So what
5:49:45I've described here this is what people
5:49:47think of usually pulmonary circulation.
5:49:50But now I want you to think of bronchial
5:49:52circulation and that has systemic
5:49:54collateral influence and that comes from
5:49:55the aorta. So here's our heart. It's
5:49:57like a little boot comes from the aorta
5:49:58and the interccoal arteries and it
5:50:01supplies oxygenated blood to bronchi and
5:50:04the lung parankma and the visceral
5:50:06plura. And that can bypass blocked
5:50:09pulmonary arteries and maintain the
5:50:10profusion. And on the right side the
5:50:12right bronchial artery typically comes
5:50:14off of the interccoal artery and it
5:50:17supplies the right lung and that
5:50:18includes the upper lobe. And so the
5:50:20answer is the right bronchial artery.
5:50:22Bronchial arteries arise from systemic
5:50:24circulation like the aorta and cause the
5:50:26oxygenated blood to be actually given to
5:50:28what makes the lungs work. When they're
5:50:30obstructed, bronchial circulation does
5:50:32the collateral stuff. It's not
5:50:33subclavian that feeds the upper
5:50:35extremity in parts of the thorax, not
5:50:36pulmonary trunk that carries
5:50:37deoxxygenated blood. A left coronary
5:50:39artery that's for cardiac profusion and
5:50:41internal thoracic artery would be
5:50:42mediastinum and the chest wall supply
5:50:44not used in the lung parankma. All
5:50:46right, so there's the explanation and
5:50:48they're going to try to, you know,
5:50:49confuse you with all sorts of different
5:50:50arteries that they could flow at you.
5:50:51For instance, they might talk about the
5:50:53brachiophalic that supplies the head,
5:50:55the neck, and the right arm.
5:50:57Brachioalic, not the lungs, though. They
5:50:59might say is the left pulmonary artery.
5:51:01Well, that supplies the left lung, not
5:51:03the right side. So, if they're asking
5:51:04about the left, maybe, but that's not
5:51:06the right answer. The internal thoracic
5:51:08supplies the anterior chest wall and the
5:51:10sternum, not the lungs. And the right
5:51:11coronary supplies the heart. So, the way
5:51:13to think about this is you have
5:51:14pulmonary arteries. Those are
5:51:15deoxxygenated blood into the avoli and
5:51:17then the bronchial arteries the systemic
5:51:18oxygenated blood to the bronchi visceral
5:51:20plura and the supporting lung tissues.
5:51:22So the pulmonary system is for avoli
5:51:25bronchial is for the plura the prankma
5:51:28and it does more collateral stuff. In
5:51:29this question we have a 29year-old woman
5:51:30presenting with palpitations excessive
5:51:32sweating and anxiety after delivering a
5:51:34baby. She had unintentional weight loss
5:51:36despite a normal appetite. She denies
5:51:37neck pain or tenderness. 98.2 her 105 BP
5:51:42122 over 82. Her thyroid is
5:51:44symmetrically enlarged but non- tender.
5:51:46Free T4 is high. TSH that's low. 24-hour
5:51:50radio iodine uptake is super high. And
5:51:52the anti thyroid proxidized antibbody is
5:51:54positive. What's the cause? All right.
5:51:56Now, this one is kind of hard to see
5:51:58sometimes on test day, but there's going
5:51:59to be somebody who recently had a baby
5:52:01and they're feeling nervous, tremulous,
5:52:03they have some weight loss. There's
5:52:05basically thyroid symptoms. They have a
5:52:07firm, non-tender, enlarged thyroid. And
5:52:11there's low TSH and high or normal free
5:52:14T4. There's usually low radioactive
5:52:16iodine uptake. But what happens is you
5:52:18actually release that thyroid hormone
5:52:20from the thyroid gland in what is
5:52:22actually a form of subacute lymphocyic
5:52:24thyroiditis called postpartum
5:52:25thyroiditis. And this is seen within one
5:52:28year postpartum. And the pathophys is
5:52:30kind of crazy. Basically there's a
5:52:31lympositic infiltration of the thyroid
5:52:34gland and then it destroys the
5:52:36follicles. Just just absolutely wrecks
5:52:38them. And that releases obviously
5:52:40pre-formed T3 and T4. So now you have
5:52:44transients like oh my gosh we have all
5:52:45this T4 but then it's followed by a
5:52:48hypothyroid phase because it's not going
5:52:49to last forever. And then the gland is
5:52:51not making new hormone and so there's
5:52:52not going to be iodine uptake needed. So
5:52:54it's postpartum thyroiditis. Autoimmune
5:52:56stimulation would be Graves. Iodine
5:52:58induced synthesis think amiotarone not
5:53:01postpartum. Thyroid adenoma hot nodules
5:53:03have focal increased uptake not diffuse
5:53:06low uptake. TSH secretreting high TSH
5:53:09high T4 would be seen if there's low
5:53:10uptake it's a hormone leak high uptake
5:53:12hormone over production now this is
5:53:14self-limited painless thyroiditis that's
5:53:16seen and up to like one year after
5:53:17delivery transient hyper thyroid to
5:53:20hypothyroid to uyroid that's the life
5:53:22cycle of it you have low reactive iodine
5:53:25uptake and you might be wondering okay
5:53:26well why is there low uptake well that
5:53:29level that we've been talking about the
5:53:30radioactive iodine uptake that measures
5:53:32how much iodine the thyroid actively
5:53:34takes up and it's used to distinguish
5:53:36between types of hyper repair
5:53:37thyroidism. So uptake, the thyroid is
5:53:39overactive. It makes too much of the
5:53:40hormone, and that's if it's increased.
5:53:42But if the uptake is decreased, then the
5:53:44thyroid is damaged. That's pretty much
5:53:45all there is to say about that. Leaky
5:53:47gland means low uptake. All right, here
5:53:49we have a 24-year-old woman presenting
5:53:50with a 10-day history of mild itchy rash
5:53:52for the first time. She first noticed
5:53:54the single large salmon colored patch in
5:53:55her upper thigh. Few days later, she has
5:53:57small lesions on her trunk and upper
5:53:59arms. The new lesions are oval, slightly
5:54:01raised, and follow the natural skin
5:54:03lines of her back. She denies fever
5:54:05chills. She takes oral contraceptive and
5:54:07is otherwise healthy. What's the correct
5:54:08answer? All right, so it starts with a
5:54:09single oval patch on the abdomen that is
5:54:12known as Harold's patch and spreads over
5:54:13the trunk in the back. There's no
5:54:15systemic symptoms, right? There's no
5:54:17fever or chills or sweats. She's
5:54:18sexually active, but she's healthy
5:54:20otherwise. And the image has multiple of
5:54:22those oval scaly kind of looking
5:54:24lesions. Well, if you know the Herald
5:54:26patch and it's followed by that
5:54:28Christmas tree pattern, there's a rash.
5:54:30That's the classic presentation for
5:54:32petrius rosia. usually have like the
5:54:34oval scaly plaques and the langers lines
5:54:37which is like the skin tension lines on
5:54:39the trunk. It's usually viral triggered
5:54:41and self-limited and it's common in
5:54:42young adults. So the answer is B. The
5:54:45initial herald patch followed by oval
5:54:47lesions in the Christmas tree pattern
5:54:49along the langers lines. Tineia corpus
5:54:51would have annular lesions with central
5:54:54clearing. So that kind of like ring
5:54:56shape but it would not spread in
5:54:58symmetric trunk pattern and you would
5:54:59need antifungals for this. Secondary
5:55:01syphilis would be on the palms and
5:55:03soles. Psoriasis vulgaras would be
5:55:05silvery scale and that's usually seen on
5:55:07the elbows and the knees. Starts with
5:55:09that solitary oval salmon colored leion
5:55:11that shows up first on the thigh or the
5:55:13trunk and then you get plaques that kind
5:55:14of look like kind of like those like
5:55:17Christmas wreaths on the back of the
5:55:18abdomen. And there's no systemic signs.
5:55:20Usually just goes away on its own. All
5:55:21right, that's that question. By the way,
5:55:23if you're finding this helpful, please
5:55:24consider liking and subscribing. It
5:55:25really makes a big difference for the
5:55:26channel. Also, we just launched
5:55:29ivymed.net the beta. So, go ahead and
5:55:31check that out. And if you want to
5:55:32tutor, just visit IvyTutoring. There
5:55:34you'll be able to get access to
5:55:36one-on-one tutoring with a Harvard
5:55:37graduate like myself. It's a good way to
5:55:39guarantee the past step one. All right.
5:55:40So, in this question, we have a
5:55:4242-year-old man, could be a female as
5:55:43well. Presents to the emergency
5:55:45department with severe upper abdominal
5:55:46pain that began suddenly 2 days ago. He
5:55:48describes the pain as sharp, constant,
5:55:50and radiating to the back. What's that?
5:55:52While you think I've just updated the
5:55:54patient demographics, you can actually
5:55:55visualize this exact patient in addition
5:55:57to another demographic. But this should
5:55:59be making you think of acute
5:56:00pancreatitis. Constant. It's the sharp
5:56:02constant radiating to the back kind of
5:56:04thing. Nausea. Vomited twice since the
5:56:06onset. He drinks approximately 8 to 10
5:56:08beers daily and has done so for a long
5:56:09time. He feels ill. He's got a fever.
5:56:11Abdomen is distended. He's got some
5:56:13discoloration because of bruising below
5:56:15his skin noted around the umbilycus.
5:56:17Look at that lipase level. Holy cow.
5:56:19That's a cute pancreatitis. That's your
5:56:21cue. You also have low calcium. It's got
5:56:23acute pancreatitis written all over it.
5:56:25Honestly, now why is this a cute
5:56:26pancritis? Why were we like, "Oh my
5:56:28gosh, this is obvious." It's cuz there's
5:56:30a triad of symptoms. And the first one
5:56:32is epigastric pain that radiates to the
5:56:36back. Let me move this guy so you can
5:56:37see my notes here. Gastric pain that
5:56:39radiates to the back. That's the first
5:56:41thing. You also have nausea or vomiting
5:56:43for the second thing. And the third
5:56:45thing is a history of gallstone or
5:56:47alcohol. And the specific physical sign
5:56:49is the gray turner sign. That's the
5:56:50echimosis of the flanks. And that's
5:56:52because of the retroparitinal
5:56:54hemorrhaging. And that's just the
5:56:55hemorrhaging, pancreatitis. So
5:56:57gallstones, obesity, diabetes, and
5:56:59actually female is going to be another
5:57:01risk factor as well. But a huge dead
5:57:04giveaway. If they're super nice to you,
5:57:06super crazy nice. Then they're also
5:57:08going to show you the elevated amalayise
5:57:10and lipes, especially lipes. As you can
5:57:13see in this question that I made for you
5:57:14guys, look at this lipase level. My
5:57:16goodness, have you ever seen a lipase
5:57:18level that high? Acute pancreatitis. All
5:57:20right, so here the trap answers.
5:57:21perforated peptic ulcer that would cause
5:57:23free air to be in the diaphragm but you
5:57:25don't have any mention of that eskeemic
5:57:26colitis would be elderly bloody diarrhea
5:57:29watershed areas alcoholic hepatitis
5:57:31would be as greater than ALT and the
5:57:33transaminases are mild alcoholic and
5:57:37choleiccyitis that's right upper
5:57:39quadrant pain and this is actually
5:57:40important to know so I'm going to write
5:57:41this down for choleaccyitis you should
5:57:43think of right upper quadrant pain
5:57:45Murphy sign as well and gallstones and I
5:57:48want to get into this in a second but
5:57:49just before I do I want to explain about
5:57:50The pancreas looks like this. I know
5:57:52beautiful drawing, right? But in acute
5:57:54pancreatitis, you have autodigestion of
5:57:56the pancreas by pancreatic enzymes. And
5:57:58that causes there's this pneumonic that
5:58:00you have to know. Get smashed. And G is
5:58:03gallstones. E is ethanol. T is trauma. S
5:58:06is steroids. M is mumps. A is
5:58:09autoimmune. S is scorpion. H is
5:58:12hypercalcemia and also hyper
5:58:15triglyceridemia. E is ERCP. And D stands
5:58:18for drugs. And the drugs there could be
5:58:20like as aoprne, fruomide, thioides,
5:58:23balproate
5:58:25that kind of thing. Now it's important
5:58:26to know that this is not shos triad or
5:58:29acute chingitis. That's the right upper
5:58:31quadrant pain, the fever, the jaundice
5:58:33because in that there's no back pain or
5:58:35there's there's also no gray there's no
5:58:38gray turner sign. And it's not a rupture
5:58:40of the AAA cuz that would be in older
5:58:42males with shock and a pulsatile mass.
5:58:45They're typically not going to give you
5:58:46a woman for this. In my experience, it's
5:58:48not a ruptured ectopic thing that have
5:58:50vaginal bleeding. And some signs to look
5:58:52out for literal signs are like colon
5:58:54sign. That's an hemorrhagic
5:58:55pancreatitis. And the big thing to look
5:58:57out for is lipes. They love asking about
5:58:59lipes with acute pancreatitis. That's
5:59:01number one. And then the number one
5:59:02cause of acute pancreatitis is the G and
5:59:04the get smashed. It's the gallstones.
5:59:07And the complications there are
5:59:08pseudosis, necrosis, hemorrhaging, ards,
5:59:10and hypocalcemia. So look out for those
5:59:12gallstones, alcohol, gray turner. And
5:59:15the gray turner sign by the way is that
5:59:16bluish discoloration the echimosis of
5:59:18the flanks due to the retroparitinal
5:59:20hemorrhaging and that usually happens
5:59:21like 24 48 hours after the bleeding
5:59:23begins. That's gray turners. The colon
5:59:25sign is also seen in the hemorrhagic
5:59:27pancreatitis. There's also this thing
5:59:29that's not tested but like it's called
5:59:30the fox sign which is pretty cool.
5:59:32That's like really severe pancreatitis
5:59:34and that's like located in like the
5:59:35upper thigh ingueno ligament area. But I
5:59:38promised that I would go back to this
5:59:39choleicitis because it's super
5:59:41important. The choleicitis versus
5:59:42pancreatitis. So acute choicyitis would
5:59:45have right upper quadrant pain whereas
5:59:47acute pancreatitis would have epigastric
5:59:49pain to the back. This guy would be seen
5:59:50with Murphy sign and that's like the
5:59:52inspiratory arrest on the right upper
5:59:54quadrant palpation whereas we talked
5:59:55about the other signs for acupancitis
5:59:57like gray turner colon sign and the
5:59:58triggers are going to be gallstones for
6:00:01both but acupancritis also likes alcohol
6:00:04in the question stems and usually for
6:00:06bolicyitis you look at the lipase levels
6:00:08and they're normal and that's why I made
6:00:09a big deal out of this lipase level
6:00:11because in pancreatitis lipase is
6:00:13elevated every single time and usually
6:00:15you'll see some sort of a gallstone with
6:00:17this one whenever you do imaging on
6:00:19choleiccyitis and on pancreatitis you
6:00:21have a CT scan you see a swollen
6:00:23pancreas you might see some pseudocystis
6:00:26or something like that and the treatment
6:00:27for colicyitis is a colcystectomy but
6:00:29the treatment for acute pancreatitis
6:00:30would be like IV fluids you know pain
6:00:32control that kind of stuff also you know
6:00:33mo no per nothing by the mouth treatment
6:00:37for acute pancreatitis so rapid quiz the
6:00:40two signs that suggest retroparitinal
6:00:41hemorrhaging and pancritis what are they
6:00:43colon sign the umbilicus and then the
6:00:45gray turner sign which is the flanks
6:00:46what's the test of choice for
6:00:47diagnosingitis
6:00:49Right upper quadrant ultrasound. Right
6:00:51upper quadrant. Remember, very different
6:00:52than pancreatitis. What test is used? If
6:00:54right upper quadrant ultrasound is
6:00:55equivocal, but you still have the sus
6:00:57suspicion for it, you do a h high scan.
6:00:59You know that nuclear medicine which is
6:01:01involved in nuclear medicine. All right,
6:01:03I think we explained that pretty well.
6:01:04If you found this helpful, please
6:01:05consider liking and subscribing. Visit
6:01:07the new website. Just doing this to be
6:01:08as helpful as possible. It'd be great if
6:01:10you could spread awareness of this
6:01:12channel. We'll see you guys in the next
6:01:13video. Hello everybody. Welcome back. We
6:01:15only have 20 questions more to go. So
6:01:17get that popcorn popping and let's learn
6:01:18the most important content you will need
6:01:20to know by the time you take step one.
6:01:22For our first question, we have a
6:01:2329-year-old woman presenting to the
6:01:25gynecology clinic for evaluation of
6:01:27primary infertility. As part of her
6:01:29workup, she underos a fllororoscopic
6:01:30procedure involving contrast ejection
6:01:32into the cervix to assess the uterine
6:01:34and tubal architecture. Imaging reveals
6:01:36symmetrical opacification of the uterine
6:01:38cavity. Bilateral narrow linear
6:01:41structures extending laterally. In
6:01:42contrast, materials seen diffusely in
6:01:44the pelvis beyond the tubes. She reports
6:01:46no discomfort. What's the interpretation
6:01:48of her finding? So she is taking a
6:01:49hysterero salpingoggram and it looks
6:01:51like it's showing that there are patent
6:01:52tubes which is a normal finding and so
6:01:54the answer is normal finding indicating
6:01:56tubal pedency. All right. So the way to
6:01:58think about this is the fallopian tubes
6:02:00are the only direct passage between the
6:02:02inside of the reproductive tract and the
6:02:04open abdominal cavity. Contrast in the
6:02:07parishium does not indicate that there
6:02:09is a leak. It only means that the tubes
6:02:11are open. And if they're open that means
6:02:13they are working. That's how God made
6:02:14them. And it's very common for you to
6:02:16think, oh man, the contrast in the
6:02:17parisian that means there's a rupture.
6:02:19But a rupture would show irregular
6:02:21outlines and also really chaotic
6:02:23extravisation and also you would be
6:02:25presenting with pain and bleeding.
6:02:27That's not the case here. So in a
6:02:28hysterosalping
6:02:30or HSG, you have contrast injected into
6:02:33the cervix to evaluate the uterine
6:02:35cavity and the fallopian tube patency.
6:02:37And a normal finding is smooth contour
6:02:40linear filling of bilateral fallopian
6:02:42tubes and there should be free contrast
6:02:44spillage into the peritineal cavity.
6:02:46That would be normal for the fallopian
6:02:48tube. All right, moving on to the next
6:02:50question. All right, for this one we're
6:02:51going to talk about choleiccytoinine
6:02:52CCK. It's released in response to fatty
6:02:55acids in the datadinum. So it stimulates
6:02:57that pancreatic enzyme secretion,
6:02:59gallbladder contraction, and bile
6:03:00release. Here's our question. An
6:03:02investigator studying a gastrointestinal
6:03:04hormone secretion in response to
6:03:05different macronutrients. On trial, a
6:03:08mixture rich in long fatty acids is
6:03:10delivered. What is observed? The answer
6:03:13increased choicesin. Fatty acids
6:03:15stimulate CCK release from eye cells.
6:03:18They also might ask you about the
6:03:19sphincter of OD relaxation to digest the
6:03:21fats. So the small intestine actually
6:03:24has hormone sensing cells and they
6:03:26detect whenever they see fat and they
6:03:29send chemical instructions to the
6:03:31pancreas and the gallbladder. Increased
6:03:33GIP would stimulate insulin. VIP is for
6:03:37secretary diarrhea. Motelin would be
6:03:39inhibited by food intake. Those are
6:03:41related to fasting and migration motor
6:03:43complexes. So fasting states for motelin
6:03:45suppressed gastrin that would mildly
6:03:47occur with fatty acids but it's not the
6:03:49main mechanism at play for fatty acids
6:03:52in the dwatinum stimulating those CCK
6:03:54that's CCK release. The goal is to
6:03:56maximize lipid digestion. All right. In
6:03:58our next question, a 24year-old graduate
6:03:59student is enrolled in neuroscience
6:04:01research examining the neural effects of
6:04:03psychoactive drugs. During the study,
6:04:05she receives a dose of simulant compound
6:04:07and her brain activity is monitored via
6:04:09functional MRI. The imaging shows
6:04:11increased activity in the nucleus
6:04:12encumbent, prefrontal cortex and VTA?
6:04:15These findings most likely reflect
6:04:16increased neurotransmission in which
6:04:18pathway? So we have noradenergic,
6:04:21serotic, dopamineergic, coneric and
6:04:24GABA? This is a dopamine pathway in the
6:04:26VTA. And they could make it more
6:04:28difficult and ask which of the dopamine
6:04:30pathways is it? And if they ask that
6:04:32it's important to know the misoortical
6:04:34and the misolyic dopamineergic pathways
6:04:36are the key circuits underlying drug
6:04:38reinforcement and addiction. And the VTA
6:04:41vententral tegmental area projects
6:04:43dopamine to the nucleus ccumbent the
6:04:45misolyic pathway and the nucleus
6:04:47ccumbent then projects to the prefrontal
6:04:49cortex and that's through the
6:04:50misoccortical pathway. So that's the
6:04:52pathway and that misoccortical pathway
6:04:55through to the prefrontal cortex
6:04:56mediates the conscious experience of
6:04:58pleasure and craving and compulsory
6:05:01nature drug seeeking that kind of stuff
6:05:03and virtually all drugs of abuse of
6:05:05cocaine and opioids nicotine alcohol and
6:05:08sedative hypnotics increased dopamine
6:05:10release somehow in those pathways. Now
6:05:12let's look at why these answers are
6:05:13wrong. Norinergic would be associated
6:05:15with arousal memory and encoding.
6:05:17Serotonin is mood regulation. It's
6:05:19disregulated in depression.
6:05:22would be prefrontal cortex associated
6:05:23attention and learning. GABA is
6:05:26associated with the cotta nucleus motor
6:05:27inhibition. So once again it's that VTA
6:05:30that sends the dopamine rich projections
6:05:32to the nucleus encumbent that's the
6:05:34pleasure hub and then it loops in with
6:05:35the prefrontal cortex. So in this
6:05:37student they're increasing the
6:05:38activation of the nucleus ccumbent the
6:05:40VTA and the prefrontal cortex and that
6:05:41is why she is feeling the dopamine rush.
6:05:43Now you might ask why is not an
6:05:44endorphin? Well endorphins are actually
6:05:46not for step one going to be recognized
6:05:47as reinforcement pathways. Endogenous
6:05:50opioids can modulate dopamine but they
6:05:52do not directly go through those
6:05:53pathways. The norineric the
6:05:55norepinephrine through the locuselius
6:05:57increases alertness and arousal. All
6:05:59right. In our next question we have
6:06:01could be a man or a woman but in this
6:06:02case it's a 59year-old woman with a
6:06:04history of hyper lipidmia and diabetes
6:06:07presents to the ED with crushing
6:06:09subternal chest pain radiating to her
6:06:11left arm. She reports increasing
6:06:12frequency of similar episodes in the
6:06:13past. ST depressions and leads four to
6:06:16six. Which the following substance is
6:06:17most likely prevented from binding.
6:06:20Droponum one is elevated. She's
6:06:21administered aspirin, clipadil,
6:06:23nitroglycerin, and heperin. And an IV
6:06:26medication that inhibits the final step
6:06:27of aggregation. So if it's aggregation,
6:06:29it's going to be fibbrinogen. And our
6:06:30answer is indeed C. And for this one, we
6:06:32have to know our GPS. GP2B3A
6:06:35on activated platelets is the final
6:06:37common pathway for aggregation because
6:06:39its extracellular domain binds
6:06:41fibbrinogen which cross links the
6:06:42adjacent platelets and so a biximab will
6:06:45block the GP2B3A and prevent
6:06:47fibbrronogen binding and it also will
6:06:49halt the propagation of the thrombus.
6:06:51ADP to P2Y12
6:06:54would be platelet activation and
6:06:56upregulation that is blocked by
6:06:57clpitadil not bymab. Adenazine increased
6:07:00camp. It'd be anti-agregatory
6:07:03and serotonin is released from dense
6:07:05granules. A way to think about this is
6:07:07vonilbrand factor binds gp1b for
6:07:10adhesion and fibbrronogen binds gp2b 3a
6:07:15for aggregation and biximmab is going to
6:07:18block this latter pathway. Fibbrinogen
6:07:20allows platelet cross-linking and
6:07:22aggregation. Unstable angine and stemi
6:07:24is what this patient was suffering from
6:07:26and so they gave aiximab to block that
6:07:28interaction and halt the thrombus
6:07:30growth. Brandon is adhesion. Thromoxin
6:07:32A2 is vasa constriction and platelet
6:07:34activation but it's upstream. Serotonin
6:07:35is released from the granules and ADP
6:07:38stimulates pllet activation. So it
6:07:40promotes that expression but it does not
6:07:41bind it. So it's the final step in that
6:07:43platelet aggregation pathway is the
6:07:45protein GP 2B3A. Next, we have a
6:07:48six-month-old boy brought to the clinic
6:07:50due to persistent coughitis media and
6:07:51several episodes of pneumonia since he
6:07:53stopped breastfeeding. His birth history
6:07:55is unremarkable. He has no palpable
6:07:57lymph nodes or tonsils. Cytometry shows
6:07:59absence of IGM. Well, it's not going to
6:08:01be hyperigg syndrome then. It's going to
6:08:03be xlink a gamoglobanmia. Flowcytometry
6:08:06shows some normal CD3T cells and absent
6:08:09or near absent IGMs. Those are B cells.
6:08:12And that would be the classic failure
6:08:13for B cell maturation. And it's these
6:08:15infections that begin after 6 months.
6:08:17And why is it after 6 months? Because
6:08:19that's when the IGG will start to wne
6:08:22from the mother. And the ideology is BTK
6:08:24brutin tyrosine kynise mutation. It's X
6:08:27linked and it blocks the preB to
6:08:30immature B development. And so you have
6:08:31a very low B cell count and
6:08:33panhypoglobinia.
6:08:35So that would be low IGG, low IGA, low
6:08:39IGM, low IG. You'll have small or absent
6:08:42tonsils and lymph nodes and though
6:08:44almost every single time are going to
6:08:46try to make you think that it's
6:08:47something else like skid but that would
6:08:49be decreased T- cells and B cells. It
6:08:51would have basically a low CD3 positive
6:08:54count as well and also opportunistic
6:08:56infections would be present. Hyperiggm
6:08:58would have normal B numbers with high
6:08:59IGM hence the name. Selective IgA
6:09:02deficiency would have normal B and T
6:09:03cell numbers only the IgA would be low
6:09:06and mo deficiency would be neutrfil
6:09:08killing defect and the lymphosy
6:09:09phenotype would be normal. Okay, for
6:09:11this next one, I just wanted to speak
6:09:13very briefly because it's kind of easy.
6:09:14It's just acne in athletes and military
6:09:17trainees. It can be due to friction. You
6:09:19can treat it with retinoids which
6:09:21decrease the keratinization, benzyl
6:09:23peroxide or antibiotics. Here's some
6:09:25myths about acne. And they might say,
6:09:26"Hey, we have a 17-year-old male who has
6:09:29eruption on his back and shoulders after
6:09:30he's wearing pads during practice. What
6:09:32is the contributing factor? It's
6:09:34mechanical irritation from sports
6:09:35equipment. Acne can be caused by the
6:09:37follicular occlusion, increased sebum
6:09:39production, and then the bacteria gets
6:09:41trapped there. That's what's happening.
6:09:42It's not the fatty food, and it's not a
6:09:44fungal infection like malisthesia
6:09:46because that would not have the
6:09:46comedones. So, yep, you're wearing a
6:09:48helmet, you're playing football. Watch
6:09:50out for this. In our next question, we
6:09:51have a 24-year-old woman presenting with
6:09:53concerns about increased facial hair and
6:09:55difficulty losing weight. You should
6:09:57already be thinking of some PCOS, coarse
6:09:59hair on the jawline, and indeed it is
6:10:01polycystic ovarian syndrome. Super easy
6:10:03diagnosis. Oligummenorhea, iritism,
6:10:06obesity, elevated LH and FSH ratio. No
6:10:09signs of realization or cushioning good
6:10:11features, but they do have that kind of
6:10:12facial hair growth just a tiny bit.
6:10:15They're the trap answers why they're
6:10:16wrong, but watch out for irregular menes
6:10:18and also this is due to obesity which
6:10:20increases the risk of insulin resistance
6:10:22and you have polycystic ovaries on
6:10:24ultrasound. Androgen secretreting
6:10:26ovarian tumor is wrong because they
6:10:28don't have clitoromegaly or deepening
6:10:29voice and testosterone is elevated but
6:10:31not dramatically high. Cushing syndrome
6:10:34that presents with the stry moon faces
6:10:35in the buffalo hump but you don't see
6:10:37those signs. She lacks central obesity
6:10:39and proximal muscle weakness. Idiopathic
6:10:42heretism. It's not idiopathic because
6:10:45the cycles were abnormal. Primary
6:10:47hypothyroidism, fatigue and weight gain
6:10:49and bradic cardiac cold intolerance
6:10:50would be seen. And this is actually
6:10:51super common. About 10% of reproductive
6:10:53age women. All right, there are the
6:10:55buzzwords. All right, here's another
6:10:56relatively easy one. 20-year-old man
6:10:58comes emergency department. Look at that
6:11:00pressure 196. So I would immediately
6:11:02start thinking of bifio chromosytoma and
6:11:03so the next step would be start
6:11:05phoxybenzamine before surgery could be a
6:11:07male or a female as you can see here
6:11:09here's an example of a patient you give
6:11:11alpha adinergic blockade with
6:11:12phoxybenzamine it's non- select to be
6:11:14reversible to to prevent the
6:11:15hypertensive crisis and so there's a
6:11:17triad here it's peroxismal headaches
6:11:19palpitations and refractory hypertension
6:11:21if you're put on a beta blocker like
6:11:23mtopriol without an alpha blockade
6:11:25they're not going to actually worsen the
6:11:26crisis because you get unopposed alpha
6:11:27adinergic constriction this comes from
6:11:29the chromophin cells the neural press
6:11:31cells in the adrenal medulla and you
6:11:32should do a 24-hour urine catakolamine
6:11:35medinephrine screen because the
6:11:36metinephrines are going to remain
6:11:37elevated between the attacks and on
6:11:39preop you have to do it's imperative
6:11:42that you do an alpha blocker first like
6:11:44phoxybenzamine or doxyosen doxyosen and
6:11:47then the beta blocker so you can expand
6:11:49the volume with the fluids and for the
6:11:51genetics you should think of men 2 a 2b
6:11:54you know the r von hippolindow or NF1
6:11:56screen in young patients so it's
6:11:58episodic catakolamine surges and you
6:12:00diagnose them with metinephrines and you
6:12:02have to treat the alpha before the beta
6:12:04and then you do surgical resection. So
6:12:05you can't get propanol first or ledol
6:12:08even though that has mixed alpha and
6:12:10beta activity. Definitely you cannot
6:12:12observe somebody's viochromes. Well, you
6:12:14just want to watch somebody die. So the
6:12:16answer is not E. For the next question,
6:12:18we have a 32-year-old man. Could also be
6:12:19a female here. Blood pressure 168 over
6:12:22106. We got a high pitch brew in the
6:12:24left upper quadrant. Plasma's renin at
6:12:26200 on the left and then 12 on the
6:12:28right. We can see some narrowing of the
6:12:30left renal artery. The vasa constrictor
6:12:32responsible for this is produced where?
6:12:34The answer pulmonary endothelial cells.
6:12:36And the reason why is because angotensin
6:12:381 is converted to angioensin 2 by the
6:12:40ACE AC located at the pulmonary vascular
6:12:43endothelium. And this condition is known
6:12:46as renovvascular hypertension from the
6:12:48right renal artery stenosis like an
6:12:51abdominal brewy. And so what happens is
6:12:53you have decreased renal profusion and
6:12:54that causes the juxtolular cells to then
6:12:57release renin that converts
6:12:58angotensinogen into angotensin 1. Then
6:13:01angotensin converting enzyme ACE in the
6:13:03pulmonary endothelium converts
6:13:04angotensin 1 into angotensin 2. That's a
6:13:08potent vasoc constrictor that raises
6:13:10blood pressure and so the vasoc
6:13:12constrictor emerges from the pulmonary
6:13:13vascule. And so the answer is D.
6:13:16Renomaculadensa would be detecting the
6:13:18tubular sodium chloride and signals the
6:13:20cells but does not make angotensin.
6:13:22Adrenal zonopiculata for that you should
6:13:24think of cortisol glio basement membrane
6:13:27is involved in filtration and the hpatic
6:13:29cinosidal endothelium would be
6:13:31angotensinogen and so angotensin 2 is
6:13:34the systemic vasoc constrictor that
6:13:35increases the systemic vascular
6:13:37resistance and preferential epherent
6:13:39arterial constriction. It maintains the
6:13:41GFR. So for therapy here you do
6:13:43revascularization, angoplasty or stent.
6:13:45For fibrouscular dysplasia or critical
6:13:48stenosis you give like an ARB or an ACE
6:13:50inhibitor as well and unilateral disease
6:13:53but that could also precipitate acute
6:13:55renal injury and bilateral renal
6:13:58arterial stenosis by dropping that
6:14:00epherent tone. All right, for this one
6:14:02we have a 65-year-old woman with poorly
6:14:03controlled hypertension started on new
6:14:05medication. 2 weeks later she reports
6:14:07new onset ankle swelling and occasional
6:14:09headache. Her pressure has decreased
6:14:11from 168 to 130. We have some pitting
6:14:13edema though which mechanism explains
6:14:15the hypertensive effect of this drug.
6:14:16Okay, the answer is going to be the
6:14:18decreased arterial resistance but we
6:14:20have to know the drug dihydropiritin
6:14:22calcium channel blockers act primarily
6:14:23on the vascular smooth muscle. Examples
6:14:25of this would be like emloopene and they
6:14:28block the LT type calcium channels in
6:14:31the vascular smooth muscle and that
6:14:32causes arterial vasoddilation which then
6:14:35decreases the SVR which is the afterload
6:14:37and decreases the blood pressure and it
6:14:39has a minimal effect on the heart rate
6:14:40and the contractility unlike non
6:14:42dihydroparodines like dilotism and these
6:14:45dihydropiritine calcium blockers are
6:14:47first line anti-hypertensives especially
6:14:49in black patients and those with
6:14:51isolated systolic hypertension so the
6:14:53elderly and common side effects can the
6:14:55peripheral edema and the way that I like
6:14:56to remember that is you think of these
6:14:58as legs and you think of this as the
6:14:59edema because it's the LT type
6:15:00peripheral edema from arterial dilation
6:15:03which then increases the capillary
6:15:04hydrostatic pressure it's not increased
6:15:07capacitance of the venus vessels
6:15:08nitrates would work there not calcium
6:15:10blockers that'd be veno dilation B
6:15:12decreased cardiac contractility that'd
6:15:14be seen with vapimal dilotiz not
6:15:17dihydropodines
6:15:18suppression of sympathetic outflow would
6:15:20be a central alpha agonist like
6:15:22clonedine and reduction of intravascular
6:15:24volume would be natures, thioides and
6:15:26lute diuretics. Now 50 million Americans
6:15:28are treated for high blood pressure and
6:15:30this is the drug that only targets the
6:15:31blood vessels not the heart dihydroperod
6:15:33and calcium blockers like
6:15:34emloopeneapene.
6:15:36Heart rate is affected by beta 1
6:15:38adinuric antagonists like mtopylol and
6:15:40propanol. The blood volume can be
6:15:42affected by diuretics. The veins
6:15:44affected by nitrates but CCBs are
6:15:46anti-hypertensives that inhibit the
6:15:48calcium influx and that causes
6:15:49vasoddilation and decreased arterial
6:15:52resistance. All right, this one is super
6:15:54simple, so we'll go quickly. An
6:15:558-year-old girl is admitted after
6:15:57prolonged exposure to chemical fire in a
6:15:58factory near her home. She develops
6:16:00worsening dismia, hypoxia, diffused
6:16:02bilateral infiltrates on chest X-ray. A
6:16:04novel agent is designed to mitigate the
6:16:06inflammatory cascade. What is it? The
6:16:08answer is interlucan 10. Interlucan 10
6:16:11is the anti-inflammatory one. And ARDS
6:16:13is a diffuse inflammatory lung injury
6:16:15where you have increased capillary
6:16:17permeability and proteinrich edema and
6:16:20you have decreased compliance and a VQ
6:16:21mismatch. And that damage is driven by
6:16:23the pro-inflammatory cytoines like TNF
6:16:25alpha, IL1 and the neutrfils recruitment
6:16:28and activation and also NFPAPA B
6:16:30mediated gene programs. So IL 10 is
6:16:33anti-inflammatory and so it helps with
6:16:34ARDS. It inhibits the activated
6:16:36macrofasages. It decreases the MHC2
6:16:40expression and also TH1 cytoines will be
6:16:44decreased by IL10 and examples of those
6:16:46would be like IL2 or interferon gamma.
6:16:50And so it dampens the inflammatory
6:16:51cascade, lowers I2, lowers interferon
6:16:54gamma. Now IL6 is a cute phase reactant.
6:16:56Interferon gamma is a macrofase
6:16:58activator. So it kind of does the
6:16:59opposite here. GM CSF would be a
6:17:01granular site booster and lucatream B4
6:17:03is involved in chemotaxis. For our next
6:17:06question, we have a 52-year-old woman
6:17:07presenting with eight months of
6:17:09worsening shortness of breath and a dry
6:17:10cough. She has a 15-year history of
6:17:12renods phenomenon. High resolution shows
6:17:14bilateral basil reticulations and
6:17:16honeycombing. Which of the following is
6:17:18most likely the cause of the patient's
6:17:20symptoms? All right, so this is
6:17:21pulmonary involvement and sclerodma.
6:17:23This person has systemic sclerosis
6:17:25scleroderma. And we know this because
6:17:26they have renods. That's when the hands
6:17:28turn really white in the cold and also
6:17:30diffuse skin thickening of the face, the
6:17:32neck, the shoulders, the arms, the
6:17:34fingers. And there's also esophageal
6:17:36reflux and dismatility, joint stiffness,
6:17:38and progressive disysmia and a dry
6:17:40cough. And you have dermal collagen
6:17:42deposition. And so the answer to this
6:17:44question, which of the following is most
6:17:45likely the cause is going to be
6:17:47interstatial lung fibrosis because of
6:17:49that diffuse sclerosis? The interstitial
6:17:51lung is the complication. The
6:17:52honeycombing supports pulmonary
6:17:54fibrosis. Answers on why they're wrong.
6:17:56Cryptogenic has subaccute flu-l like
6:17:58symptoms and patchy avular infiltrates.
6:18:00That's not going to be sclerodma.
6:18:01Pulmonary ambolism that'd be super
6:18:03acute, not gradual fibrosis. Chronic
6:18:06bronchitis would have a productive
6:18:07cough. And small cells is a
6:18:09paraneoplastic syndrome. And there's no
6:18:11smoking history here. So pulmonary
6:18:12fibrosis is super serious. It's one of
6:18:14the leading cause of death in patients
6:18:15with a systemic sclerosis. So they have
6:18:17skin tightening, renods, gird and a dry
6:18:20cough, sclerodma. It's fibrosis of the
6:18:22avular septa and reticulations and
6:18:24honeycombing will really help you lock
6:18:25in that answer. And this can progress to
6:18:27pulmonary arterial arterial hypertension
6:18:29from the vascular remodeling. But the
6:18:31primary parneal process is definitely
6:18:33definitely going to be fibrosis. And
6:18:35there's some other answers as well like
6:18:37they could have given you emphyma or
6:18:38something that's obstructive caused by
6:18:40smoking. Also you could see alpha 1
6:18:42antitrien not fibrosis. They could also
6:18:45try to get you with granulomatus
6:18:46inflammation like sarcoid tuberculosis A
6:18:48or GPA not sclerodma though. Lung
6:18:51cancers like PNA or PE would not match
6:18:54that chronic course. And then
6:18:56bronchiacttois has a bunch of recurrence
6:18:58infections. Cystic fibrosis cartaginers
6:19:00that kind of stuff. All right the next
6:19:02question we have a 62-year-old man
6:19:03history of chronic tobacco use
6:19:04presenting with progressive headaches.
6:19:06MRI shows heterogeneously enhancing
6:19:08lesions on the right parietal lobe with
6:19:10surrounding edema. Biopsy shows
6:19:11malignant cells with high nucleus to
6:19:13cytoplasmic ratio. Iminohistochemistry
6:19:15shows positivity of cytoin. Very
6:19:17important there. And so what is it going
6:19:19to be then? Well, cytoin and so it's
6:19:21probably going to be epithelial cell and
6:19:22that probably would suggest a metastatic
6:19:24carcinoma as well. But cytoins are the
6:19:26intermediate filaments of the epithelial
6:19:28origin. And the brain mass whose tumor
6:19:30cells stay positive for cytoarotin most
6:19:33likely would be like a metastatic
6:19:34carcinoma epithelial would not primarily
6:19:37be like a gle or a neuronal tumor. And
6:19:40so there are some markers that you have
6:19:41to know that I'll write down. Some of
6:19:42the most important markers are for
6:19:44epithelial astroytes mezenime muscle and
6:19:48also the neurons. So epithelial would be
6:19:51cytoarotin. Aststerytes is GFAP.
6:19:54Mezenine would be vimementin. Muscle is
6:19:56desine. And the neurons would be
6:19:58neuropilament. So epithelial is
6:20:00cytoarotin. So you think of desine, he's
6:20:02like a really strong guy. Think of your
6:20:04own thing for GFAP. Epithelial, I like
6:20:06to think of that like the keratinization
6:20:08neuro with neurons and it makes it
6:20:10pretty simple to memorize that. So
6:20:12cytoin positivity means epithelial
6:20:14derivation. And so if it's a brain mass
6:20:16or something like that, it might be a
6:20:17metastatic carcinoma from the epithelial
6:20:19origin. And that's why the answer is
6:20:21epithelial even though it's in the
6:20:22brain. So epithelial would be metastatic
6:20:24to the brain. And it's all because of
6:20:26how that's stained cytoin. Smooth muscle
6:20:28would be desine with the muscle origins.
6:20:30Astressy would be GFAP endothelial cell
6:20:33is CD3134 and a neuron neuropilament
6:20:36neuron neuropilament. So really it's
6:20:37just a onetoone matching game and it's
6:20:39cytoin positivity in this particular
6:20:41question. In our next question, we have
6:20:43a 59year-old man with a history of
6:20:45mantle cell lymphoma beginning his first
6:20:46cycle of anti- CD20 monoconal antibbody
6:20:49therapy. 30 minutes into the infusion,
6:20:51he develops rigorous diffused muscle
6:20:53aches and a fever. His blood pressure
6:20:54and respiratory rate are stable. He has
6:20:56no rash, wheezing, or facial swelling.
6:20:58What is the most likely cause of the
6:20:59symptoms? Well, we got a fever. We got
6:21:01muscle aches after an infusion. So, it's
6:21:03going to be a cytoine storm. Okay, so
6:21:05there is our nice man. I actually think
6:21:07I'm going to generate somebody who's
6:21:08like 59 years old. He looks very young.
6:21:10And this is actually something you
6:21:12really have to look out for in minutes
6:21:13to hours because nearly half of the
6:21:15patients receiving their first retoximab
6:21:17infusion will experience some sort of a
6:21:19reaction cytoine release syndrome driven
6:21:21by the B cells. And we know retoximab
6:21:24binds to the CD20 on the B cells and
6:21:26that triggers their activation and when
6:21:27they break down it causes TNF alpha and
6:21:29IL6 and those guys are troublemakers.
6:21:31They'll cause the fever, chills, muscle
6:21:33pain but it's not histamine or
6:21:35definitely not anaphilaxis. So
6:21:37compliment mediated would be
6:21:38hemoglobinura and jaundice. Mass cell
6:21:41deganulation, udicaria, hives, bronco
6:21:43spasm, activation. Antibbody dependent
6:21:46would be natural killer cells if it's
6:21:48cellular cytotoxicity if it's cellularly
6:21:50cytotoxic. And serotonin syndrome would
6:21:53cause hyperflexia and clonus and
6:21:55agitation. All right, so there is the
6:21:57new updated photo for that last
6:21:58question. And now we're already on to a
6:22:00new one. And here we have a 72-year-old
6:22:03woman. This could be a man as well as
6:22:04undergoing evaluation for persistent
6:22:06fatigue and an unintentional weight
6:22:07loss. Imaging reveals retroparitinal
6:22:09mass and biopsy shows poorly
6:22:11differentiated cells with high nuclear
6:22:13to cytoplasmic ratios.
6:22:15Aminohistochemistry reveals the tumor
6:22:18cells lack expression of MHC class1.
6:22:20Flytometry of the patient's peripheral
6:22:22blood shows an increased activity of
6:22:23CD56. These lymphosytes are most likely
6:22:26to induce apoptosis of the tumor cells
6:22:28through which mechanism? All right. The
6:22:29answer for inducing apoptosis is the
6:22:31recognition of cells that lack the MHC1
6:22:34expression. This is a classic feature of
6:22:35many tumors. And you might say, hey,
6:22:37I've seen fast and fast L that's
6:22:39involved in death. And yes, it's seen in
6:22:41T- cell mediated apoptosis, but not the
6:22:44natural killer shell method. That is a
6:22:46totally different mechanism. Natural
6:22:47killer cells preferentially destroy
6:22:48malignant tumor cells with decreased or
6:22:50absent MHD class one expression. That's
6:22:53their whole deal. They're like, you have
6:22:55a passport, you have a passport. Oh, I
6:22:57don't see your MHD class one expression.
6:22:59you're dead. That's how it works. IL2
6:23:01and interferon gamma secretion that
6:23:04would be activating the macrofasages and
6:23:05T- cells, not direct cytotoxicity. And
6:23:08AD86 is the T- cell stimulation that's
6:23:10irrelevant to the natural killer cells
6:23:12which don't have those receptors. And
6:23:13these natural killers are first
6:23:14responders. Basically, you're holding up
6:23:17every single cell is holding up this
6:23:19thing, the MHC1 that's like don't kill
6:23:21me. And sometimes these tumor cells,
6:23:24they're being really clever and they
6:23:25just delete that and but then they
6:23:27delete that to avoid detection. but it
6:23:28it ends up killing them because the
6:23:30natural killer cells are like, "You
6:23:31don't have a passport." And they just
6:23:33attack them. All right, our next topic
6:23:35that we're going to cover is actually
6:23:36going to be an ethics question. You need
6:23:38to make sure you ask open-ended
6:23:39questions and you validate and recognize
6:23:41that emotional states can change. And
6:23:43so, you have to check people's
6:23:44understanding. You don't give stats and
6:23:46premature reassurance. All right, so we
6:23:47got a dude surgical resection. He's
6:23:50like, "Hey, I finished, but I still feel
6:23:51scared. What should I do now?" What do
6:23:52you say? You say, "You sound concerned.
6:23:54Can you tell me more about what's
6:23:55worrying you right now?" Open-ended is
6:23:57what you need. Can you tell me more?
6:23:58Like what are you specifically afraid
6:24:00of? That's what you need to be asking in
6:24:01these scenarios. Open-ended questions if
6:24:03somebody expresses concern so that you
6:24:05can ask for their understanding and then
6:24:07you can tailor the discussion according
6:24:08to their gaps and their needs and their
6:24:10concerns. But first, you have to ask. By
6:24:12the way, we just launched Ivy Med, which
6:24:14helps you master every major exam. If
6:24:16you want a Harvard tutor who teaches the
6:24:17ACT, SAT, MCAT, USMLE, any of that, then
6:24:20just visit ivytutoring.net. All right,
6:24:22for this one, it's super simple. Burnt
6:24:24sugar odor. That's due to isolucine
6:24:27metabolism byproducts. You'll see a baby
6:24:29with vomiting, lethargy, hypotonia, 3 to
6:24:31seven day old infant onset after feeding
6:24:33starts. Branch chain amino acids
6:24:35accumulate. It's an autotoal recessive
6:24:36inheritance and you get keto acidosis
6:24:38and cerebral edema because of those
6:24:40elevated branched chain keto acids.
6:24:42There's a deficient enzyme of the branch
6:24:44chain alpha keto acid dehydrogenase
6:24:46complex that causes these guys to build
6:24:49up the branch chain ones. And leucine is
6:24:51neurotoxic so it causes encphylopathy in
6:24:53a coma and it smells like burnt maple
6:24:55syrup. That's all you need to know for
6:24:56this. So, we got a young kiddo. Poor
6:24:57feeding, irritability. He was healthy,
6:24:59but now he can't. Now he's got a sweet
6:25:01odor. Maple syrup. It's a deficiency in
6:25:03what? Branch chain alpha ketoid keto
6:25:06acid. Super simple. One of the easiest
6:25:08questions out there. And that's a cute
6:25:10little photo of that neonate there for
6:25:12that question. Here's some other ones on
6:25:14why they're wrong. Ornithine transcarba
6:25:16would be ura acid defect, hypermonia,
6:25:18not sweet smelling. Homogen oxidase
6:25:20would be aptanura with a dark urine.
6:25:23Cythion beta synthesis will lead to the
6:25:26morphenoid habitus lens dislocation not
6:25:28minionates. All right, next one. We have
6:25:30a 27y old man. I guess we can use this
6:25:32guy. There he is. Goes to the clinic
6:25:34after injuring his right middle finger
6:25:35while rock climbing. He slipped.
6:25:37Ouchies. And he has a sudden pop in his
6:25:39finger. He was gripping and he held it.
6:25:41All right. So now, what structure is
6:25:43damaged? This is a memorization one.
6:25:44It's the flexure digtor fundus. And the
6:25:46way that I like to remember this one is
6:25:48the jersey finger. Because if you're
6:25:49ever playing flag football and you drag
6:25:51get somebody's jersey like this guy's
6:25:52rock climbing he goes then you are going
6:25:54to be damaging the flexor digtorum
6:25:56profundus and it's funny because it
6:25:58seems like a small injury but I'm like
6:25:59oh that was a profound injury it just
6:26:01helps me remember it radial nerve
6:26:02supplies the extensors not the flexors
6:26:04flexor digtorum superficialis flexes the
6:26:06pip not the dip pip not the dip see the
6:26:10difference digtorm superficialis and
6:26:12this one is the dip so superficial the
6:26:14ular is involved in digits four to five
6:26:17and intrinsic hand muscles Extensor
6:26:19controls the index finger extension like
6:26:22that. So, high yield msk flex dtor
6:26:24profundus. There it is. Jersey finger.
6:26:26Yep. You can't flex the dip joint. And
6:26:28now for our last question. We're almost
6:26:30there, guys. You're one question away
6:26:33from watching Futurramama or whatever it
6:26:34is you like to do. Walking your dog, who
6:26:36knows, going and working out.
6:26:3862-year-old woman presents with
6:26:39progressive left axillary swelling for
6:26:42the past 3 months. She denies fever,
6:26:44night sweats, and weight loss. Physical
6:26:46exam shows 3 cm firm non-tender lymph
6:26:49node in the left axilla. Excision biopsy
6:26:51shows preserved nodular architecture
6:26:53with small cleave cells. And we got CD19
6:26:5710 BCL2 positive and monocomal cappa
6:26:59light chain restriction and there is no
6:27:01expression of your T- cells CD5 or CD23.
6:27:05Which of the following abnormalities is
6:27:06the most likely characteristic? All
6:27:08right. Did you get this one right? Do
6:27:09you know what the answer is? So on
6:27:11questions like this you have a firm
6:27:12slowly growing cervical node over like
6:27:15maybe two months it's an endolin course
6:27:17and they talk about maybe on CDs on the
6:27:20flowcytometry they talk about CD19
6:27:22positivity what's that that's a B cell
6:27:24they might also mention CD10 what's that
6:27:25that's the germinal center marker and
6:27:27that's actually a hallmark for something
6:27:28what is it a hallmark for that's right
6:27:30for you guys in the back that said it
6:27:31good job that my friends is the giveaway
6:27:33CD10 is the giveaway because faux
6:27:35folicular folicular lymphoma light chain
6:27:39restriction is something you could also
6:27:40mention as well and on histology you
6:27:42have the nodular follicular architecture
6:27:44I wonder why bcl2 positivity and that
6:27:47bcl2 positivity is actually from the T14
6:27:51to 18 the transllocation it's the IGBC2
6:27:55transllocation and there we there we
6:27:57have it guys the answer is C because
6:27:59this person has felicular lymphoma 14
6:28:02follicular 14 follicular lymphoma bcl2
6:28:06overexpression remember that F sound 14
6:28:09follicular Now 11 to 14 11. Look at all
6:28:13those L's. 1 1 1 1. That's how you know
6:28:17that 1 one1 has all the L's because it's
6:28:20mantle cell. Look three L's in that.
6:28:23There are three L's in that and there
6:28:24are three ones in this. That's how you
6:28:26remember mantel is 11 to 14. 814 is a MC
6:28:30transllocation seen in Burke kids
6:28:31lymphoma. You remember this because it's
6:28:33mixed. You have a kid who's 8 years old
6:28:36and you have like an adolescent and it's
6:28:37mixed demographic there. Burk kid, which
6:28:40would be a rapidly growing mass. And
6:28:42then the 922. For this one, I like to
6:28:43envision a Philadelphia football player
6:28:46wearing a jersey with 922, and that's
6:28:48CML or BLLL, not slow growing lymphas.
6:28:52And a deletion would be seen in chronic
6:28:55lympositic leukemia. So, we have a
6:28:56transllocation that hijacks that BCL2
6:28:58gene and lets them cheat death. They can
6:29:01never die. Which, by the way, I think
6:29:03that humans will get there. I think
6:29:04anticnesscent technology is reaching the
6:29:06point that in my lifetime there will be
6:29:07some people who are born who won't die
6:29:10for hundreds if not thousands of years
6:29:11wild to think about. That's the
6:29:12importance of getting an education. But
6:29:14yes, I digress. This is felicular
6:29:16lymphoma. It's indolent germinal centers
6:29:18bell lymphoma. CD19 positivity, CD10
6:29:21positivity, BCL2 positivity, light chain
6:29:24restricted often is going to be T1418
6:29:27transllocation. All right, so remember
6:29:28your CD markers. You should be good to
6:29:30go. Congratulations guys, we did it. Can
6:29:32you believe it? We have finished 200 of
6:29:35these original questions. They're done.
6:29:37If you guys found this helpful, then
6:29:39please share ivymed.net or
6:29:41ivtutoring.net to your friends. We're
6:29:43launching a step one prep course as you
6:29:45can see here. Now, a lot of this is
6:29:46still in beta, but we have our
6:29:48analytics. We have an entire medical
6:29:49library and the goal is to make this
6:29:51totally free and extremely cheap for you
6:29:54guys as we continue to add more
6:29:55features. But we're making an
6:29:57interactive medical library with
6:29:58question banks, with flashcards
6:30:00integrated into Onkey. can also plug in
6:30:02to other things like UWorld. This is
6:30:04going to be amazing. So, visit
6:30:05ivymed.net
6:30:07and visit ivytutoring right here,
6:30:08ivytutoring.net if you'd like a
6:30:10one-on-one tutor. That's a way that you
6:30:12can guarantee that you'll pass step one.
6:30:13You know, it's one thing to just chant
6:30:14it and just study like crazy, which I
6:30:16encourage you to do. Watch all these
6:30:18videos, pass this silly exam. It is a
6:30:20silly exam. It's just a bunch of
6:30:21factoids. But if you really want to make
6:30:23sure that you pass it like 100%, then
6:30:25just visit ivytutoring.net, fill out the
6:30:27form, and we'll give you a Harvard tutor
6:30:28who's going to make sure that you pass
6:30:29the exam. Guys, you're troopers. Thanks
6:30:31for sticking with it. I love reaching
6:30:33out to you guys, interacting with the
6:30:35community. I want to build like a super
6:30:36positive community here. There's some
6:30:38students who email me, which by the way,
6:30:40email me at [email protected],
6:30:42and they'll say, "Hey, I just can't do
6:30:44any more studying for the day." And I'm
6:30:45like, "No worries. I got to send out
6:30:47some emails. I got some work calls that
6:30:48I got to make. Why don't we just hop on
6:30:50a Zoom call? You can just sit there on
6:30:51the other side and I'll put a Pomodoro
6:30:53timer on and we can just get through
6:30:54this exam." I really deeply care about
6:30:56you guys and I want to make sure that
6:30:58you're taking care of yourself in this
6:30:59prep time. Dedicated period is like
6:31:01crazy. It's not a psychologically like
6:31:03balanced time and you need to take care
6:31:04of your mental health, your physical
6:31:05health. Make sure you guys are working
6:31:07out. Make sure you're going on runs,
6:31:08taking your dog for a walk. One of the
6:31:10greatest ironies of medicine is that we
6:31:11do too little prepare and prevent and
6:31:14way too much repair and repent. As a
6:31:16future physician, you are sacrificing
6:31:18your mid to late 20s, your early 30s so
6:31:20that you can help other patients who are
6:31:22suffering. That's very commendable. But
6:31:23don't disregard your health, physical
6:31:25and mental, as you prepare for this
6:31:27test. Remember, if you're struggling, no
6:31:29thought is final. Tomorrow's going to be
6:31:31a new day. You can always reinvent
6:31:32yourself. The only thing we actually
6:31:34have in life is the present. Everything
6:31:36else is either a memory or a best guess
6:31:38about what's going to happen in the
6:31:39future. Reframe those best guesses with
6:31:41cognitive behavioral therapy. Make sure
6:31:43that you selft talk in a way that's
6:31:44positive and try to find a lot of
6:31:46fulfillment as you go through your
6:31:47medical career. Really excited for you
6:31:48guys. Thank you so much for coming
6:31:50along. Thanks for liking and
6:31:51subscribing. If you didn't, thank you
6:31:53for just being out there, for putting in
6:31:54the good work every single day of your
6:31:56life, for helping other people, for
6:31:57showing up today for others and for
6:31:59yourself. Give yourself a pat on the
6:32:01back. And with that, all I'll say is
6:32:03we'll see you in the next video. You
6:32:04guys take care.
6:32:04>> For me, it's pretty hard to know.
6:32:10[Music]
6:32:12I think you really do that.
6:32:15I guess this time I'll go.
6:32:19[Music]
6:32:22Do you hear me?
6:32:28[Music]
6:32:33Do I miss you?
6:32:42[Music]
6:32:45I can't listen what you say. I can't
6:32:48handle what you're talking about.
6:32:54So
6:32:56I really didn't mean
6:32:59but how can you possibly know
6:33:07I keep forgetting what we're talking
6:33:08about. I wish you could listen
6:33:14to the night in the kitchen when we were
6:33:17kissing.
6:33:21I miss spending time with you.
6:33:27[Music]
6:33:50You have to give a little
6:33:54that you stay mine.
6:33:56[Music]
6:34:00You still tell her it all
6:34:04and I fret when you're alive.
6:34:12How do I get
6:34:18[Music]
6:34:23away?
6:34:26I do it all the time.
6:34:31[Music]
6:34:34We keep forgetting what we're talking
6:34:36about. I want you to see what you're
6:34:38missing.
6:34:40I wish we could stop
6:34:43sitting in the sea.
6:34:48I'm missing time with you.
6:34:54[Music]

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