Official Step 1 High Yield Concepts Thread

[Transposony]

---

Members don't see this ad.

Let's discuss our doubts/offer clarifications about mechanisms/concepts for Step 1

ASK ANY QUESTIONS here.

To kick start the thread here is something I didn't know:

1. Penicillin-binding proteins (PBPs) are actually enzymes (transpeptidases & carboxypeptidases) which cross-link peptidoglycan. Penicillins binds to these enzymes and inactivating them thereby preventing cross-linkiing of peptidoglycan.

2. Periplasmic space (Gram -ve) contain proteins which functions in cellular processes (transport, degradation, and motility). One of the enzyme is β-lactamase which degrades penicillins before they get into the cell cytoplasm.
It is also the place where toxins harmful to bacteria e.g. antibiotics are processed, before being pumped out of cells by efflux transporters (mechanism of resistance).

There are three excellent threads which you may find useful:

List of Stereotypes

Complicated Concepts Thread

USMLE images

 

[stepone2015]

What germ layer is the cornea from? UW says surface ecto, DIT said neural crest.

Outter epithelial layer is surface ectoderm. Rest is neural crest.

 

[aspiringmd1015]

regarding the germ layers. Men2a is associated with the RET gene, which controls neural crest migration. But why are the parathryoids effects in this? arent the parathyroid glands made from the endoderm? Bc it makes sense why pheo occurs and why medullary Ca of the thyroid occurs

 

[aspiringmd1015]

or bc the pth glands come from the 3rd pouch? are the pouchers neural crest derived or something

 

[stepone2015]

regarding the germ layers. Men2a is associated with the RET gene, which controls neural crest migration. But why are the parathryoids effects in this? arent the parathyroid glands made from the endoderm? Bc it makes sense why pheo occurs and why medullary Ca of the thyroid occurs

I don't know for sure, but I do know that RET is involved with other cancers as well. Papillary thyroid cancer also can involve the RET gene, so it's possible RET plays an important part of parathyroid growth.

 

[aspiringmd1015]

i read soem previous post of the well respected transposony saying that bile acid sequestrants cause gall stone formation, but it doesnt right? also im not 100% on the mechanism behind fibrates causing gallstones. Any help?

 

[aspiringmd1015]

with EHEC, does the renal failure occur bc of the decreased BF to the kidney, or bc of verotoxin inhibiting protein synthesis within the kidney itself?

 

[seminoma]

***UWSA2 question. *** Ignore if you don't want to see it.



Question says that a group of patients with a specific HLA haplotype do not mount an IgG response against an injected recombinant viral protein. The question is something like "which of the following is likely to be defective in these patients?".

Two answer choices that I think make sense. 1. Antigen presentation by B cells. 2. Antigen recognition by T cells.

Correct answer is #1. Basically the explanation describes MHC1 vs MHC2 and then says that patients with MHC that do not bind (recognize) the antigen will not be able to present them to T cells. That makes sense to me. But isn't part of the MHC2-Ag-Tcell complex CD4/TCR interacting with the APC-MHC and without that interaction the T cell doesn't recognize the antigen and doesn't secrete cytokines to promote IgM --> IgG class switch?

So how can we pick one answer over the other?

Edit: Is this related to the fact that B cells don't need CD4 help to class switch to IgG? So even with ****ty CD4-interaction, B cells can adequately mount an IgG response on their own?

 

[aspiringmd1015]

^wow, didnt know that. Thought it was compulsory for th2 cells for the class switch. How does adrenal insuffieciency cause ovarian failure? i was thinking increased ACTH which would increase androgens, aromatize, shut off fsh and lh, so no ovulation, but with adrenal insufficiency, your reticular would be shot too no?

 

[psylocke]

***UWSA2 question. *** Ignore if you don't want to see it.



Question says that a group of patients with a specific HLA haplotype do not mount an IgG response against an injected recombinant viral protein. The question is something like "which of the following is likely to be defective in these patients?".

Two answer choices that I think make sense. 1. Antigen presentation by B cells. 2. Antigen recognition by T cells.

Correct answer is #1. Basically the explanation describes MHC1 vs MHC2 and then says that patients with MHC that do not bind (recognize) the antigen will not be able to present them to T cells. That makes sense to me. But isn't part of the MHC2-Ag-Tcell complex CD4/TCR interacting with the APC-MHC and without that interaction the T cell doesn't recognize the antigen and doesn't secrete cytokines to promote IgM --> IgG class switch?

So how can we pick one answer over the other?

Edit: Is this related to the fact that B cells don't need CD4 help to class switch to IgG? So even with ****ty CD4-interaction, B cells can adequately mount an IgG response on their own?

#1 Makes sense...The CD4+/ TCR binds to MHC2-(processed)ag on the surface of the B cell, but it's the B cell that's initially required to bind the whole antigen first in order to present it. The T cells don't recognize the antigen per say, but rather peptide fragments of the antigen loaded on the MHC2. Perhaps that's the distinction they were testing?

Re your edit: B cells don't need CD4 help for ab production and class switching in cases of thymus independent antigen.

 

[aspiringmd1015]

if its a thymud independent antigen, it wouldnt class switch though correct? it would stay as an igM producing antibody.
Does raloxifenes antagonist effect on the endometrium only work premenopausally? or is it also a postmenopausal effect

 

[psylocke]

if its a thymud independent antigen, it wouldnt class switch though correct? it would stay as an IgM producing antibody.
Does raloxifenes antagonist effect on the endometrium only work premenopausally? or is it also a postmenopausal effect

It would mostly be IgM. If you review the literature however, there are models with evidence of class switching in response to TI antigen, yet there is debate about how substantial and lasting those antibodies are.
http://jem.rupress.org/content/203/2/305.full
http://www.nature.com/icb/journal/v86/n6/full/icb200817a.html

 

[aspiringmd1015]

With PBC, why does the pruritis mostly manifest at night? i was maybe thinking bc at night you become alkalotic so maybe that has something to do with it(like PNH) but couldnt make the connection.

 

[seminoma]

with EHEC, does the renal failure occur bc of the decreased BF to the kidney, or bc of verotoxin inhibiting protein synthesis within the kidney itself?

Going to say decreased RBF because of microthrombi. Never learned about toxin effects outside the intestine so my guess is that means they are irrelevant.

With PBC, why does the pruritis mostly manifest at night? i was maybe thinking bc at night you become alkalotic so maybe that has something to do with it(like PNH) but couldnt make the connection.

Pretty sure bile acid synthesis peaks early AM and then again in the evening/night. The pruritus isn't entirely due to BDG in the blood (evidenced by the fact that pruritus precedes jaundice in the pathogenesis), but the circadian nature of bile acid and cholesterol synthesis is my best guess.

 

[seminoma]

FA (pg 274) says beta blockers decrease contractility "(acutely)". What is the "acutely" getting at?

 

[aspiringmd1015]

beta blockers allow for greater filling of the myocardium dont they, how does erythryomycin cause cholestasis?

 

[seminoma]

beta blockers allow for greater filling of the myocardium dont they, how does erythryomycin cause cholestasis?

They do, but that doesn't affect contractility.

 

[CodeRedDew]

FA (pg 274) says beta blockers decrease contractility "(acutely)". What is the "acutely" getting at?

I think the "acutely" implies that it isn't a chronic/irreversible change vs. something like dilated cardiomyopathy. I'm not 100% sure though, but that's what I took it as. So in essence, beta-blockade → ↓ cAMP → ↓ intracellular calcium → acute reduction in contractility (since contractility is dependent on the amt. of intracellular Ca2+) -- Idk if I answer your question lol

 

[lovemango]

i read soem previous post of the well respected transposony saying that bile acid sequestrants cause gall stone formation, but it doesnt right? also im not 100% on the mechanism behind fibrates causing gallstones. Any help?

Look up UW QID #67 & 165. The explanations mention that fibrates suppress cholesterol 7a-hydroxylase activity → increased concentration of cholesterol in bile. Bile acid resins reduce hepatic cholesterol, which activates HMG-CoA reductase and thus also increase the cholesterol in bile, leading to gallstones.

 

[seminoma]

FA says the funny current is "mixed Na/K inward current". The funny-current channels follow the usual rule of sodium influx and potassium efflux though, right?

 

[Transposony]

Pretty sure bile acid synthesis peaks early AM and then again in the evening/night. The pruritus isn't entirely due to BDG in the blood (evidenced by the fact that pruritus precedes jaundice in the pathogenesis), but the circadian nature of bile acid and cholesterol synthesis is my best guess.

Could relative sensory deprivation at night as compared to daytime may also be a contributing factor ?
The same reason the toothache is worse at night.

 

[aspiringmd1015]

Look up UW QID #67 & 165. The explanations mention that fibrates suppress cholesterol 7a-hydroxylase activity → increased concentration of cholesterol in bile. Bile acid resins reduce hepatic cholesterol, which activates HMG-CoA reductase and thus also increase the cholesterol in bile, leading to gallstones.

i see, but with resins i thought it was the deficiency of the actual bile salts that played a bigger role, with being unable to solubulize the cholesterol, thus a "relative" cholesterol deficiency

 

[psylocke]

FA says the funny current is "mixed Na/K inward current". The funny-current channels follow the usual rule of sodium influx and potassium efflux though, right?

It's an inward current of Na+ and K+ (permeability ratio Na+/K+ of 0.2)...
When the channel gets activated by hyperpolarization there's an inward flow of both K+ and Na+ but more of the latter.

 

[seminoma]

i see, but with resins i thought it was the deficiency of the actual bile salts that played a bigger role, with being unable to solubulize the cholesterol, thus a "relative" cholesterol deficiency

More like a relative bile salt deficiency. Poop out all your bile salts = pisses off the liver = liver takes up more LDL to make more cholesterol to make more bile salts. Excess cholesterol and not enough bile salts to solubilize it = cholesterol gallstones.

 

[aspiringmd1015]

btw any idea on the erythryomycin cholestasis effect? or is this idiopathic

 

[seminoma]

Nitrates + Beta blockers. Additive or synergistic? Have found info saying both.

 

[seminoma]

Does apical V/Q increase or decrease with exercise?

 

[psylocke]

Does apical V/Q increase or decrease with exercise?

V/Q should decrease and approach 1 (compared to normal when apical V/Q is 3) ...But you're question has me thinking what factors in to this, is it only due to the increase of blood flow to the upper areas because of the increase in capillary recruitment?

 

[stepone2015]

V/Q should decrease and approach 1 (compared to normal when apical V/Q is 3) ...But you're question has me thinking what factors in to this, is it only due to the increase of blood flow to the upper areas because of the increase in capillary recruitment?

I think it's: increase resp rate -> decr PACO2 -> cap dilation in that region
The compensatory incr cardiac output goes there (decr resistance as well) and pushing V/Q towards 1.

 

[seminoma]

V/Q should decrease and approach 1 (compared to normal when apical V/Q is 3) ...But you're question has me thinking what factors in to this, is it only due to the increase of blood flow to the upper areas because of the increase in capillary recruitment?

Yup, I think it's a good question to test your understanding of regional differences in V/Q. It seems counterintuitive that V/Q would ever decrease and I think it would be an easy mistake to make under stress/test pressure.

I think it's: increase resp rate -> decr PACO2 -> cap dilation in that region
The compensatory incr cardiac output goes there (decr resistance as well) and pushing V/Q towards 1.

PaO2 and PaCO2 are normal in exercise and that makes me think PAO2 and PACO2 are also normal (not decreased PACO2). Hyperpnea (vs hyperventilation) 2/2 the increased PvCO2 and decreased PvO2 doesn't overcompensate or cause a reduced PACO2. I believe the main mechanism is increased CO from increased SV and HR causes apical vasodilation and making zone 1 (PA>Pa) more like zone 2 or zone 3 (Pa>PA).

 

[Transposony]

The balance of laboratory sensitivity and specificity requires that patients with positive HIV enzyme immunoassay results should undergo testing using the HIV western blot for confirmation. Which of the following is loaded onto the nitrocellulose paper that forms the “blot” in the HIV western blot?

A) Antibodies against viral proteins isolated from donors
B) Viral proteins
C) Viral nucleic acids
D) Viral proteins from the patient’s serum
E) Antibodies against viral proteins isolated from the patient

 

[Transposony]

A 45-year old woman presents to his family physician with a 2-month history of night sweats and fever and a cough that has been worsening over the last 3 weeks. She is a emergency department nurse in inner city Los Angeles; 3 months ago she cared for recent immigrant from Haiti with similar symptoms. His chest x-ray is positive for consolidation in the middle lobe of the right lung. What would a biopsy of affected tissue from this woman’s lung most likely reveal?

a. Deposition of antibody-antigen complexes
b. Edema with a serous exudate
c. Enlarged macrophages surrounded by lymphocytes
d. Large numbers of neutrophils within a suppurative exudate
e. Syncytia and intranuclear inclusions

 

[Transposony]

A biotechnology company is developing a vaccine against a bacterium that has been causing outbreaks of severe infections in children. The vaccine is comprised of purified proteins secreted by the bacterium in adjuvant. Clinical trials have been promising; injected children develop protective antigen-specific antibodies. Which of the following is most likely to be the most important mechanism of pathogenesis associated with this bacterium?

A) Antigenic variation
B) Biofilm formation
C) Capsule production
D) Exotoxins
E) Intracellular growth

 

[psylocke]

Yaaasss! I needed questions about lab techniques and vaccines.. They always trip me up.

The balance of laboratory sensitivity and specificity requires that patients with positive HIV enzyme immunoassay results should undergo testing using the HIV western blot for confirmation. Which of the following is loaded onto the nitrocellulose paper that forms the “blot” in the HIV western blot?

A) Antibodies against viral proteins isolated from donors
B) Viral proteins
C) Viral nucleic acids
D) Viral proteins from the patient’s serum
E) Antibodies against viral proteins isolated from the patient

B. It's the separated viral proteins after electrophoresis that are transferred.

A biotechnology company is developing a vaccine against a bacterium that has been causing outbreaks of severe infections in children. The vaccine is comprised of purified proteins secreted by the bacterium in adjuvant. Clinical trials have been promising; injected children develop protective antigen-specific antibodies. Which of the following is most likely to be the most important mechanism of pathogenesis associated with this bacterium?

A) Antigenic variation
B) Biofilm formation
C) Capsule production
D) Exotoxins
E) Intracellular growth

A... ? But the bit about clinical trials being promising is putting me off...

 

[aspiringmd1015]

last one is D, exotoxin(diptheria), and the 45 year old should be TB, so C?

 

[CodeRedDew]

The balance of laboratory sensitivity and specificity requires that patients with positive HIV enzyme immunoassay results should undergo testing using the HIV western blot for confirmation. Which of the following is loaded onto the nitrocellulose paper that forms the “blot” in the HIV western blot?

A) Antibodies against viral proteins isolated from donors
B) Viral proteins
C) Viral nucleic acids
D) Viral proteins from the patient’s serum
E) Antibodies against viral proteins isolated from the patient

E -- I'm not sure though, but this made the most sense to me since a Western involves protein.

Edit: oops, yup definitely read that wrong. Read it as "what would you add to the nitrocellulose paper" lol. Yeah I'd go with B as @psylocke said

 

[aspiringmd1015]

V/Q should decrease and approach 1 (compared to normal when apical V/Q is 3) ...But you're question has me thinking what factors in to this, is it only due to the increase of blood flow to the upper areas because of the increase in capillary recruitment?

at the same time the V/Q at the base of the lungs would increase correct? to make it = in all areas of the lung

 

[psylocke]

at the same time the V/Q at the base of the lungs would increase correct? to make it = in all areas of the lung

During exercise, because you have increased perfusion to the zone 1, the regional differences in V/Q from apex to base become less so collectively the ratio tends to 1. Think about it the way @seminoma mentioned above; the V/Q ratio in zone 1 becomes more similar to that of zone 2 and 3.

 

[aspiringmd1015]

Can CIS be labeled as a carcinoma(even though no BM invasion?) just came across a ? on UW stating DCIS as comedocarcinoma. I figured it couldnnt be comedocarcinoma although camedo is the most common form of DCIS, but the carcinoma in the name threw me off, guess i figured wrong.

 

[seminoma]

What causes RBC casts besides glomerulonephritis?

Can CIS be labeled as a carcinoma(even though no BM invasion?) just came across a ? on UW stating DCIS as comedocarcinoma. I figured it couldnnt be comedocarcinoma although camedo is the most common form of DCIS, but the carcinoma in the name through me off, guess i figured wrong.

Same issue I had with BAC the other day.

 

[seminoma]

Patient diagnosed with chronic untreated HCV presents with glomerulonephritis. Which type is it?
Same patient undergoes appropriate treatment for his acute renal injury as well as chronic HCV. He recovers from the renal damage, but months later he presents with nephrotic syndrome that you suspect was caused by his HCV treatment. Which type is it?

 

[CodeRedDew]

Patient diagnosed with chronic untreated HCV presents with glomerulonephritis. Which type is it? MPGN type 1
Same patient undergoes appropriate treatment for his acute renal injury as well as chronic HCV. He recovers from the renal damage, but months later he presents with nephrotic syndrome that you suspect was caused by his HCV treatment. Which type is it? FSGS due to IFN treatment? Can't remember if any of the other HCV drugs cause kidney damage.

 

[aspiringmd1015]

any known specific drugs that give you a false positive VDRL? drug induced lupus drugs maybe

 

[aspiringmd1015]

Can CIS be labeled as a carcinoma(even though no BM invasion?) just came across a ? on UW stating DCIS as comedocarcinoma. I figured it couldnnt be comedocarcinoma although camedo is the most common form of DCIS, but the carcinoma in the name threw me off, guess i figured wrong.

my bad, comedocarinomas straight out of FA, shouldve seen it, pg 590. fack

 

[aspiringmd1015]

Vit C toxicity's a/c with calcium oxalate stones, is this because vitamin C enhances oxalates absorption? or does it acidify the urine? Goljan also mentions that vitamin C toxicity can cause uric acid stones, so im assuming its because it acidifies the urine?

 

[stepone2015]

Vit C toxicity's a/c with calcium oxalate stones, is this because vitamin C enhances oxalates absorption? or does it acidify the urine? Goljan also mentions that vitamin C toxicity can cause uric acid stones, so im assuming its because it acidifies the urine?

Acidification may play a role, but I believe the main cause is because vitamin C competitively binds Tamm-Horsfall protein in the urine, which normally would have bound oxalate. Increasing free oxalate in the urine increases the risk of forming calcium oxalate stones.

 

[aspiringmd1015]

so theres no assocation with uric acid stones then?

 

[stepone2015]

so theres no assocation with uric acid stones then?

Uric acid can also bind Tamm-Horsfall to prevent crystallization. XS vitamin C can cause UA stone formation as well. Left that bit out, sorry.

 

[stepone2015]

75 year old woman presents to the ER with tachypnea, confusion, and excessive thirst. Her son, who brought her in, explains that she was diagnosed over 20 years ago with type 2 diabetes mellitus that had been controlled with insulin, and she has Alzheimer's disease. Finger stick shows a significantly elevated serum glucose, and blood labs reveal a wide anion gap acidosis and significant ketonemia.

What is the pathogenesis for her current condition?

 

[CodeRedDew]

75 year old woman presents to the ER with tachypnea, confusion, and excessive thirst. Her son, who brought her in, explains that she was diagnosed over 20 years ago with type 2 diabetes mellitus that had been controlled with insulin, and she has Alzheimer's disease. Finger stick shows a significantly elevated serum glucose, and blood labs reveal a wide anion gap acidosis and significant ketonemia.

What is the pathogenesis for her current condition?

Not sure, but is it destruction of pancreatic islet cells via pancreatic adenocarcinoma; poor prognosis.

 

[dfib slim]

75 year old woman presents to the ER with tachypnea, confusion, and excessive thirst. Her son, who brought her in, explains that she was diagnosed over 20 years ago with type 2 diabetes mellitus that had been controlled with insulin, and she has Alzheimer's disease. Finger stick shows a significantly elevated serum glucose, and blood labs reveal a wide anion gap acidosis and significant ketonemia.

What is the pathogenesis for her current condition?

Did she forget to take her insulin and now is in DKA?