Official Step 1 High Yield Concepts Thread

[Transposony]

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

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[aspiringmd1015]

can someone explain the difference b/w T and L calcium channels, and class 1c prolong the ERP in AV node when they primarily work on the ventiruclar ap? is it bc they have class 1a acitivity too?

 

[faisal 2000]

why vit b12 and vit b6, and folic acid deficency can cause DVT ?

 

[Transposony]

why vit b12 and vit b6, and folic acid deficency can cause DVT ?

homocysteine accumulates?

 

[aspiringmd1015]

help.

 

[aspiringmd1015]

does somatostatin work on the enterochromaffin cell, the parietal cell, or both.

 

[faisal 2000]

MOC of Orlistat and its side effects

 

[Keto]

Orlistat is one of the "obesity drugs". Orlistat interferes with pancreatic enzymes (lipases) and causes steatorrhea.

Also important side effect is: Crystalline Nephropathy
(SOMATIC mnemonic, if it works for you: Sulfadiazine Orlistat Methotrexate Acyclovir Triamterene Indinavir Ciprofloxacin)

 

[aspiringmd1015]

Cirrhosis and TPN are a/c with pigment stones only? or also cholesterol stones? it would make sense for both, but FA has it listed under pigment stones. Also when pigment stones are formed, the stones are in an unconj form correct? as in they cant be in a conjugated form with a decreased amount of bile acid to cause them?

 

[faisal 2000]

which drugs and diseases can cause peripheral neuropathy ??

 

[aspiringmd1015]

also in FA pg 353, it states that gastrin is inc by chronic atrophic gastritis due to h. pylori, but isnt it mostly due to the autoimmune gastritis, bc AI gastritis attacks the stomach in the fundus and stomach, and thats where most of the parietal cells are located? THats what sattar mentioned at least.

 

[faisal 2000]

why Antipsychotic drugs are contraindicated in pregnancy ?

 

[aspiringmd1015]

why does FA mention right to left shunt AND V/Q mismatch as seperate causes of hypoxemia? arent shunts a V/q mismatch situation?

 

[Keto]

which drugs and diseases can cause peripheral neuropathy ??

Hi

Most common causes of polyneuropathy are diabetes mellitus, alcohol abuse and HIV. But of course you have to watch out for drug induced neuropathy.

Other etiologies of peripheral neuropathy can be broken down in nutritional (B6, B12), hereditary (Friedreich's ataxia, Charcot-Marie-Tooth), Infections (HIV, Lyme disease), and others. I will focus here on some classical examples of drug induced peripheral neuropathy.


HIV Drugs

• Nucleoside analogues (esp. Didanosine, Stavudine)

A challenge would be here to differentiate between HIV neuropathy and drug-induced neuropathy. Watch out for the classic NRTIs that cause neuropathy or a patient, that is not on triple therapy.

Chemotherapy-induced peripheral neuropathy (CIPN)

• Vincristine
• Cisplatin
• Taxanes (Paclitaxel)

Classic Example: A patient, that is on chemotherapy for weeks and develops now "stocking glove neuropathy". They will ask you is this because of the drug or because of cord compression of a metastasis? A Cord compression would give you also back pain, upper motor symptoms, prominent motor deficits.

Antimicrobial Drugs

• Isoniazid (prevent with B6)
• Linezolid

Immunosuppressive Drugs / Inflammatory drugs

• Colchicine
• Cyclosporine

Toxins

• Arsenic poisoning (chronic)

Classic Example: Wood preservatives, weed killers, pesticides.


As an interesting side note:

• Watch out for a patient with Diabetes, who is taking Metformin and develops polyneuropathy after years of treatment. Metformin interferes with the absorption of folate and B12, and the question is now: Is the neuropathy due to diabetes or B12-deficiency? (Get CBC with MCV and look for your macrocytic anemia with hypersegmented neutrophils. Measure B12 levels.

Have a great day!

 

[faisal 2000]

Hi

Most common causes of polyneuropathy are diabetes mellitus, alcohol abuse and HIV. But of course you have to watch out for drug induced neuropathy.

Other etiologies of peripheral neuropathy can be broken down in nutritional (B6, B12), hereditary (Friedreich's ataxia, Charcot-Marie-Tooth), Infections (HIV, Lyme disease), and others. I will focus here on some classical examples of drug induced peripheral neuropathy.


HIV Drugs

• Nucleoside analogues (esp. Didanosine, Stavudine)

A challenge would be here to differentiate between HIV neuropathy and drug-induced neuropathy. Watch out for the classic NRTIs that cause neuropathy or a patient, that is not on triple therapy.

Chemotherapy-induced peripheral neuropathy (CIPN)

• Vincristine
• Cisplatin
• Taxanes (Paclitaxel)

Classic Example: A patient, that is on chemotherapy for weeks and develops now "stocking glove neuropathy". They will ask you is this because of the drug or because of cord compression of a metastasis? A Cord compression would give you also back pain, upper motor symptoms, prominent motor deficits.

Antimicrobial Drugs

• Isoniazid (prevent with B6)
• Linezolid

Immunosuppressive Drugs / Inflammatory drugs

• Colchicine
• Cyclosporine

Toxins

• Arsenic poisoning (chronic)

Classic Example: Wood preservatives, weed killers, pesticides.


As an interesting side note:

• Watch out for a patient with Diabetes, who is taking Metformin and develops polyneuropathy after years of treatment. Metformin interferes with the absorption of folate and B12, and the question is now: Is the neuropathy due to diabetes or B12-deficiency? (Get CBC with MCV and look for your macrocytic anemia with hypersegmented neutrophils. Measure B12 levels.

Metronidazole and diphtheria cause peripheral neuropathy

 

[aspiringmd1015]

is berylliosis a/c w/ Caplan syndrome?

 

[faisal 2000]

is berylliosis a/c w/ Caplan syndrome?

no. Caplan syndrome associated with Coal Workers' Pneumoconiosis

 

[aspiringmd1015]

it's a/c with most of them, check FA. Only sattar said its only a/c with coal workers.

 

[faisal 2000]

how can we diagnose ankylosing spondylitis ?

 

[aspiringmd1015]

hla typing, and Ct/mri?

 

[faisal 2000]

hla typing, and Ct/mri?

i meant based on symptoms

 

[Keto]

how can we diagnose ankylosing spondylitis ?

Hi

The classical case of Ankylosing Spondylitis will be a young man (or woman (2:1)!) with slowly progressive (over several months and years) low back pain, that is worse in the morning. The patient will have morning stiffness and symptoms improve throughout the day.


Usually your imaging workup in lower back pain would be, to do an x-ray first, and then eventually move to MRI [2]. The diagnosis of Ankylosing Spondylitis is confirmed by plain film (bilateral sacroiliitis). Ankylosing Spondylitis is a seronegative spondyloarthropathy, so rheumatoid factor (RF) and anti-nuclear antibody (ANA) will be negative (other differential diagnosis would be moved down the list). Ankylosing Spondylitis is strongly associated with HLA-B27. 90% of Ankylosing Spondylitis patients will have positive HLA-B27 (but only 5% of the whole population, who are HLA-B27 positive have Ankylosing Spondylitis). So HLA-B27 is not specific for AS testing and is not necessary for the diagnosis of Ankylosing Spondylitis [1]. Watch out for extra articular features of Ankylosing Spondylitis, such as: anterior uveitis, inflammatory bowel disease, aortic regurgitation.

Have a good day!


[1] When does HLA-B27 play a role in diagnosing Ankylosing Spondylitis?
Patients can also be diagnosed with Ankylosing Spondylitis with a negative x-ray, if the MRI shows sacroiliitis or if they are HLA-B27 positive and have other features indicating spondyloarthritis (↑CRP or response to NSAIDs)

[2] When do you do generally MRI first in a patient with acute low back pain?
If you have signs and symptoms of cord compression.

 

[Keto]

it's a/c with most of them, check FA. Only sattar said its only a/c with coal workers.

Caplan syndrome occurs in two conditions:

1. Pneumoconiosis related to mining dust (silica, asbestos, coal)
2. Rheumatoid Arthritis

Caplan syndrome presents with multiple peripheral basilar nodules and airflow obstruction. These nodules are simple rheumatoid nodules [1].

Complication of caplan syndrome is the development of progressive massive fibrosis [2]. But usually, the prognosis of caplan syndrome is favorable and there is no known treatment.

[1] https://en.wikipedia.org/wiki/Rheumatoid_nodule
[2] https://en.wikipedia.org/wiki/Progressive_massive_fibrosis

Impressive x ray showing caplan syndrome:
https://iqradiosign.files.wordpress.com/2013/12/72805380.jpg

 

[Focused1]

Diseases with large platelets on P/S ?

 

[aspiringmd1015]

ITP, BS, and im sure theres others. megaloblastic anemia would cause enlraged megakaryoblasts, not sure about the platelets though.

 

[Focused1]

ITP, BS, and im sure theres others. megaloblastic anemia would cause enlraged megakaryoblasts, not sure about the platelets though.

Chediak Higashi too

Any more ?

 

[aspiringmd1015]

essential thrombocytosis

 

[aspiringmd1015]

w/ IV hemolysis, why would urobilinogen be present in your urine like FA mentions, on pg 393. Hb is water soulble and is urinated out via HB itself or as hemosiderin from the tubules. for urobilinogen to be present in your urine it would have to get conjugated by the liver first and be put in the intestine etc, but that doesnt happen w/ intravascular hemolysis?

Reason for the difference in blood lactate levels between Von Gierke and Cori disease?

youre not hypoglycemic in cori's, in VG you are, so your counter hormones are stimulated, but glucose cant be made, so gets shunted towards lactate i believe.

 

[aspiringmd1015]

how does corporphobilinogen increase in AIP?

 

[aspiringmd1015]

ven if it were to be "intermittent" it would still make heme, it wouldnt stop at coprophobilinogen

 

[Focused1]

w/ IV hemolysis, why would urobilinogen be present in your urine like FA mentions, on pg 393. Hb is water soulble and is urinated out via HB itself or as hemosiderin from the tubules. for urobilinogen to be present in your urine it would have to get conjugated by the liver first and be put in the intestine etc, but that doesnt happen w/ intravascular hemolysis?
youre not hypoglycemic in cori's, in VG you are, so your counter hormones are stimulated, but glucose cant be made, so gets shunted towards lactate i believe.

You need to understand the following pathway of sorts:

Normal: Hemoglobin in Senescent RBC --> Hemoglobin in Plasma (very less IV hemolysis) & Biliverdin and Unconjugated Bilirubin (produced in Spleen mainly EV hemolysis) --> Unconjugated bilirubin in blood bound to albumin as it itself is very lipophilic and hydrophobic --> taken up, conjugated and excreted in conjugated form into bile --> conjugated bile broken down by intestinal bacteria to Urobilinogen (Old terms Urobilin, Stercobilinogen and stercobilin replaced by ONLY urobilinogen now) --> Most Urobilinogen excreted in feces ( gives the color to feces ) --> Some reabsorbed in ileum to plasma --> Urobilinigen in Urine (gives the color)


Pre-Hepatic Jaundice/Hemolysis : Hemoglobin in RBC --> Hemoglobin in Plasma (A lot of IV hemolysis) & Biliverdin and Unconjugated Bilirubin (produced in Spleen mainly EV hemolysis) --> Some hemoglobin gets filtered into renal tubules and leads to hemoglobinuria --> More Unconjugated bilirubin in blood bound to albumin as it itself is very lipophilic and hydrophobic --> More taken up, conjugated and excreted in conjugated form into bile --> More conjugated bile broken down by intestinal bacteria to Urobilinogen (Old terms Urobilin, Stercobilinogen and stercobilin replaced by ONLY urobilinogen now) --> Most Urobilinogen excreted in feces ( more color to feces ) --> more reabsorbed in ileum to plasma --> more Urobilinigen in Urine (More color)

Post-Hepatic Jaundice:Hemoglobin in RBC --> Hemoglobin in Plasma (very less IV hemolysis) & Biliverdin and Unconjugated Bilirubin (produced in Spleen mainly EV hemolysis) --> Unconjugated bilirubin in blood bound to albumin as it itself is very lipophilic and hydrophobic --> taken up, conjugated and excreted in conjugated form into bile --> conjugated bile refluxes to blood --> Conjugated bilirubin in Urine --> No Conjugated Bilirubin in Intestines --> NOT broken down by intestinal bacteria to Urobilinogen (Old terms Urobilin, Stercobilinogen and stercobilin replaced by ONLY urobilinogen now) --> NO Urobilinogen excreted in feces ( NO color to feces ) --> Not reabsorbed in ileum to plasma --> NO Urobilinigen in Urine (NO gives the color)

Hope it helps ! (took me 10 minutes to type out! :-D )

 

[aspiringmd1015]

not sure about the first part, bc like i mentioned in the above post, w/IV hemolysis, the hemoglobin is water soluble, so it just gets urinated out, in contrast to EV hemolysis, the macrophages(ie spleen) take out the rbcs directly and eat them up, and the macrophages are what have the initial enzymes like you mentioned heme oxygenase etc.) so yeah, that wouldnt account for the question i asked,

 

[aspiringmd1015]

also, why isnt there a sideroblastic anemia seeen w/ AIP or porphyria cutanea tardia, are the enzyme deficincies partial/episodic?

 

[Transposony]

Under safety science and quality care:

What are:
1. root cause analysis
2. culture of safety
3. avenues of reporting
4. outcomes data
5. forcing function
6. workaround
7. failure mode/effects analysis
8. effects analysis

Apparently all of these terms have appeared on the test.

 

[chronicidal]

"failure mode and effects analysis" is one term

 

[aspiringmd1015]

w/ regard to trendelenburg, if you stand on the side that is effected, the contralateral side will drop, what if you stand on the normal leg, what will happen then?

 

[Dr Z AU]

w/ regard to trendelenburg, if you stand on the side that is effected, the contralateral side will drop, what if you stand on the normal leg, what will happen then?

The pelvis will maintain it's level since the glute medius on that side is able to support the weight of the body.

Just think trendelenburg = glute med weakness = stretches under tension rather than remain isometrically contracted

 

[Focused1]

Under safety science and quality care:

What are:
1. root cause analysis
2. culture of safety
3. avenues of reporting
4. outcomes data
5. forcing function
6. workaround
7. failure mode and
8. effects analysis

Apparently all of these terms have appeared on the test.

Where do you plan on studying these from ?

 

[Transposony]

Where do you plan on studying these from ?

http://www.ihi.org/education/ihiopenschool/Courses/Pages/default.aspx

http://www.ihi.org/education/IHIOpenSchool/resources/Pages/BobLloydWhiteboard.aspx

http://app.ihi.org/lms/coursedetail...alogGUID=6cb1c614-884b-43ef-9abd-d90849f183d4

https://www.youtube.com/channel/UCr-ODu8TnpqF2sJMi1LCM4w

http://patientsafetyed.duhs.duke.edu/index.html

 

[Transposony]

"failure mode and effects analysis" is one term

Thanks.
That clearly shows my ignorance.

 

[shiralad]

great thanks

 

[Transposony]

Indirect= Free
Direct= Bound

For example, indirect Coombs test detects antibodies against RBCs that are present unbound in the patient's serum.
While direct Coombs test is used to detect the antibodies that are bound to the surface of RBCs.

Similarly, Indirect bilirubin (unconjugated) is free while direct bilirubin (conjugated) is bound to albumin.

Feel free to add/dispute this memory tool.

 

[aspiringmd1015]

if theres a new treatment, not vaccine, but treatment for a communicable disease, will that also lower incedence? i know for a rx that works for noncommunicable diseases won't effect incedence, but not sure about communicable diseases.

 

[Phloston]

Opioid-induced hypoventilation = really high-yield to know that's a normal A-a gradient.

 

[Transposony]

if theres a new treatment, not vaccine, but treatment for a communicable disease, will that also lower incedence? i know for a rx that works for noncommunicable diseases won't effect incedence, but not sure about communicable diseases.

Treatment can never lower incidence since the disease has already happened.
Only prevention can lower incidence.
For infectious diseases, reducing the pool of people with the disease (prevalence) will, over time, reduce new cases (incidence).
This is not a direct effect, rather an effect of decreased prevalence on future incidence(s) of an infectious disease.

 

[Focused1]

Opioid-induced hypoventilation = really high-yield to know that's a normal A-a gradient.

Isn't ALL Hypoventilation associated with a normal A-a gradient ?

 

[aspiringmd1015]

but treatment for a communicable disease can no? as in if i Rx a patient who has gonorrhea, and the prevelence goes down, then its less likely for a new case ie incedence to increase?

 

[Phloston]

Isn't ALL Hypoventilation associated with a normal A-a gradient ?

Yeah but think about how many patients on wards are on opioids. And heroine and organophosphate would be similar.

 

[Phloston]

if theres a new treatment, not vaccine, but treatment for a communicable disease, will that also lower incedence? i know for a rx that works for noncommunicable diseases won't effect incedence, but not sure about communicable diseases.

Treatment can never lower incidence since the disease has already happened.
Only prevention can lower incidence.

I'd be careful with wording here (i.e. using the word never). As an example, you can give oseltamivir/zanamivir for influenza A/B that are Tx but also decrease incidence.

And on that note, O/Z are the answer when they want to know which drug "decreases spread within a community." Or they'll say a drug was given and cells are "packed with virions" (because the virus can't leave the cell).

 

[Transposony]

I'd be careful with wording here (i.e. using the word never). As an example, you can give oseltamivir/zanamivir for influenza A/B that are Tx but also decrease incidence.

I think the keyword here is "treatment"
How can it decrease incidence when the disease has already happened ?
Are you saying that you can treat influenza before it has happened ?
In that case it will be primary prevention and NOT treatment.

 

[Phloston]

I think the keyword here is "treatment"
How can it decrease incidence when the disease has already happened ?
Are you saying that you can treat influenza before it has happened ?
In that case it will be primary prevention and NOT treatment.

O and Z are known treatments for existing disease (decrease prevalence). And they also prevent viral spread (decrease incidence). They do both.