Step 1 Complicated Concepts Thread

[TheSeanieB]

ASK AND ANSWER TOUGH QUESTIONS RELATED TO STEP 1.

Starting with me:
physiologic chloride shift - When CO2 diffuses into a RBC, it quickly converts with H2O to H+ and HCO3- so that CO2 will continue to passively diffuse into the RBC. The HCO3- is then excreted into the plasma by a Cl-/HCO3- exchanger. When the RBC enters the pulmonary capillaries, the process reverses. HCO3- is taken up by exchange for a Cl-. It combines with H+ to creates CO2 +H2O. The CO2 then diffuses out of the RBC and ultimately into the alveoli. This process allows for maximal CO2 excretion by a RBC.

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[tiedyeddog]

anyone have a logical reasoning of why bronchiectasis is an obstructive disease? It seems like in all of the other obstructive diseases the small bronchial airways narrow, which causes increased airflow resistance.

If bronchiectasis is pathology widening of the large bronchial structures, why is this obstructive?

Pathoma (pg 91) says there is increased air way trapping... what does this mean in relation to obstruction?

edit: never mind, think I found out why. http://thorax.bmj.com/content/55/3/198.full

large airways dilate but the small airways are made smaller by the infiltrate associated with decreased clearance and chronic infiltration.

 

[Myxedema]

Although it is true that bronchi and bronchioli become dilated in bronchiectasis, the important point in understanding the obstruction seen in this disease is the destruction of the muscle and elastic tissue. Recall that expiration is driven by the recoil of the elastic tissue (hence elastic recoil). If this elastic tissue is lost, then the driving force behind expiration is lost, which leads to air trapping inside the alveoli. This process is also found in emphysema, where loss of elastic tissue leads to decreased elastic recoil, which results in closure of small airways during expiration, which ultimately leads to air trapping.

 

[tiedyeddog]

Although it is true that bronchi and bronchioli become dilated in bronchiectasis, the important point in understanding the obstruction seen in this disease is the destruction of the muscle and elastic tissue. Recall that expiration is driven by the recoil of the elastic tissue (hence elastic recoil). If this elastic tissue is lost, then the driving force behind expiration is lost, which leads to air trapping inside the alveoli. This process is also found in emphysema, where loss of elastic tissue leads to decreased elastic recoil, which results in closure of small airways during expiration, which ultimately leads to air trapping.

So, does compliance decrease in all of the obstructive diseases? They all work via this decreased recoil principle and not just emphysema?

 

[JP2740]

LMN v.s. muscle damage. How will the patient present differently with regards to how the muscles are positioned? What causes pain in either group?

I thought in neuron damage, you'll be frozen in a position that is the opposite of it's function, if it causes flexion, you'll be fixed in extension. Is this the same for muscle damage?

 

[JP2740]

So, does compliance decrease in all of the obstructive diseases? They all work via this decreased recoil principle and not just emphysema?

compliance increases in emphysema

 

[tiedyeddog]

compliance increases in emphysema

you're right, my bad.

 

[JP2740]

you're right, my bad.

And I think the answer to your question is yes but not 100% sure.

 

[TheSeanieB]

Can someone explain the pain mechanism of GERD? I am confused bc I was under the impression that the nociceptors of the GI are only sensitive to stretch.

 

[JP2740]

Can someone explain the pain mechanism of GERD? I am confused bc I was under the impression that the nociceptors of the GI are only sensitive to stretch.

Go boil a hot cup of water and drink it with a straw and tell me what you think then lmao

 

[issey]

...

 

[223556]

Based on pedigree's alone is there away of telling autosomal dominant vs x-linked dominant appart? since both can theoretically affect men and women in every generation?

Had this same question the other day. Male to male transmission is how you determine the difference. I'll let you figure it out and you'll never forget it.

 

[loveoforganic2]

Inhaled anesthetics... High AV gradient corresponds to high tissue solubility and slow onset.... I cannot make that fact make sense for the life of me. The brain counts as a tissue I would assume..?

 

[loveoforganic2]

Also, if anyone has a ddx for absent thymic shadow, it would be much appreciated... stupid uworld.

 

[xeroun]

Also, if anyone has a ddx for absent thymic shadow, it would be much appreciated... stupid uworld.

Di George
Thymic Aplasia due to stress
Bruton agammaglobulinemia
Congenital hypogammaglobulinemia
lymphopenic agammaglobulinemia
Nezelofsyndrome
Transposition of the great vessels
Ebstein anomaly

Source

Inhaled anesthetics... High AV gradient corresponds to high tissue solubility and slow onset.... I cannot make that fact make sense for the life of me. The brain counts as a tissue I would assume..?

See Here For good explanation

 

[issey]

question about hardy weinberg:

If your giving the probability of having a disease in a population as say 1/5000 how would you calculate the carrier frequency for x linked vs autosomal recessive diseases? I think I know how to do it but I just need some reinforcement on the concepts.

thanks in advance

 

[loveoforganic2]

Di George
Thymic Aplasia due to stress
Bruton agammaglobulinemia
Congenital hypogammaglobulinemia
lymphopenic agammaglobulinemia
Nezelofsyndrome
Transposition of the great vessels
Ebstein anomaly

Source



See Here For good explanation

gracias

 

[loveoforganic2]

UW QID 595... don't really have a question... but are you kidding me? Never heard of such a thing even tangentially

 

[xeroun]

question about hardy weinberg:

If your giving the probability of having a disease in a population as say 1/5000 how would you calculate the carrier frequency for x linked vs autosomal recessive diseases? I think I know how to do it but I just need some reinforcement on the concepts.

thanks in advance

X linked recessive disease: Males have only 1 X so genotypic freq equation would differ between males and females. Males allele frequency AND Genotypic frequency: p+q =1. Females Allele frequency: p +q = 1 and genotypic frequency is p^2 + 2pq + q^2 = 1. If you know incidence of x linked disease in male then frequency is equal to q.

Females:
p^2 is frequency of XX <---- homozygote dominant
2pq = frequency of Xx. <--- They are carriers
q^2 = frequency of xx <--- They express disease

So if they say incidence of G6PD is 1/5000 in males. q = 1/5000 for that disease.
If they say incidence of G6PD is 1/5000 in Females. q^2 = 1/5000 --> q = (1/5000)^1/2.
Female carriers would be 2pq. p= 1- (1/5000)^1/2. 2((1- (1/5000)^1/2)((1/5000)^1/2)


Autosomal Recessive: No difference between sexes

Frequency of A allele = p
Frequency of a allele = q
p + q = 1
p^2 + 2pq + q^2 = 1
p^2 is frequency of AA --> homozygote dominant
2pq = frequency of Aa. <--- They are carriers
q^2 = frequency of aa <--- They express disease

So if they say the incidence of Cystic Fibrosis is 1/5000 in this population.
q^2 = 1/5000 <--- you have to be aa(or q^2) to have disease.
q = (1/5000)^1/2 <---- this gives you frequency of the a allele in population
p= 1- q --> 1- ((1/5000)^1/2) <---- This gives you frequency of A allele in population
2pq = 2((1- (1/5000)^1/2)((1/5000)^1/2)<---- These are the Aa. They are the carriers.

Hopefully that made some sense...

 

[issey]

X linked recessive disease: Males have only 1 X so genotypic freq equation would differ between males and females. Males allele frequency AND Genotypic frequency: p+q =1. Females Allele frequency: p +q = 1 and genotypic frequency is p^2 + 2pq + q^2 = 1. If you know incidence of x linked disease in male then frequency is equal to q.

Females:
p^2 is frequency of XX <---- homozygote dominant
2pq = frequency of Xx. <--- They are carriers
q^2 = frequency of xx <--- They express disease

So if they say incidence of G6PD is 1/5000 in males. q = 1/5000 for that disease.
If they say incidence of G6PD is 1/5000 in Females. q^2 = 1/5000 --> q = (1/5000)^1/2.
Female carriers would be 2pq. p= 1- (1/5000)^1/2. 2((1- (1/5000)^1/2)((1/5000)^1/2)


Autosomal Recessive: No difference between sexes

Frequency of A allele = p
Frequency of a allele = q
p + q = 1
p^2 + 2pq + q^2 = 1
p^2 is frequency of AA --> homozygote dominant
2pq = frequency of Aa. <--- They are carriers
q^2 = frequency of aa <--- They express disease

So if they say the incidence of Cystic Fibrosis is 1/5000 in this population.
q^2 = 1/5000 <--- you have to be aa(or q^2) to have disease.
q = (1/5000)^1/2 <---- this gives you frequency of the a allele in population
p= 1- q --> 1- ((1/5000)^1/2) <---- This gives you frequency of A allele in population
2pq = 2((1- (1/5000)^1/2)((1/5000)^1/2)<---- These are the Aa. They are the carriers.

Hopefully that made some sense...

wow that was awesome. thanks!

 

[Suncrusher]

Can someone explain the pain mechanism of GERD? I am confused bc I was under the impression that the nociceptors of the GI are only sensitive to stretch.

I'm unsure whether or not that is true lower down in the GI tract, but take it from someone who (embarrassingly) has had "pill esophagitis" (like a demented geriatric patient) due to taking a malarone pill about 30 seconds before flopping on a bed and falling asleep instantly due to sheer exhaustion: the human esophagus can definitely sense chemical irritation.

 

[Choo]

Inhaled anesthetics... High AV gradient corresponds to high tissue solubility and slow onset.... I cannot make that fact make sense for the life of me. The brain counts as a tissue I would assume..?

I was looking for the answer for this too. All I found was that high AV gradient reflects lipid:blood partition and means that the drug will be bound to albumin, which will make it equilibrate more slowly.

 

[loveoforganic2]

Malignant HTN a cause of secondary hyperaldosteronism

UW gave that as a fact. I was able to find one research article possibly linking it being due to renal artery thrombosis, but overall there's a dearth of information on the matter in any shape or form. I could possibly see it being d/t to too much reactive hyperplasia of the arterioles, but I'd love any additional explanation

 

[rueby25]

Can someone explain the pain mechanism of GERD? I am confused bc I was under the impression that the nociceptors of the GI are only sensitive to stretch.

Not sure where you got this idea, per se. They are typical nociceptors, though they are thought to be adenosine mediated in that area. The acid irritates the esophagus, causing the pain, just like you might expect. The poor localization can also help account for the pain perception, as reflux pain is often due to irritation much higher in the esophagus. That being said, I wouldn't worry too much about this. Doesn't seem like a terribly high yield topic...

 

[TheSeanieB]

Does anyone know what the benefit in taking an antacid is over simple baking soda which I believe is NaHCO3-?

 

[Choo]

Does anyone know what the benefit in taking an antacid is over simple baking soda which I believe is NaHCO3-?

It would taste like table salt, it has sodium and you get eliminate one less H+ compared with CaCO2.

 

[issey]

Friends,

Needed some help with a couple of quick question:

#1. 52 year old male presents with chills, sweating and dark colored urine. Physical exam is unremarkable blood analysis reveals: AST: 185. ALT: 189. Total Bilirubin: 2.9 mg/dl Direct: 1.5 mg/dl. Hep B surface antigen: negative. Abdominal images are negative for gallstones. He most likely is suffering from:

A. Drug or alcohol induced liver disease
B. Excess blood hemolysis
C. Gastric Ulcers
D. Gilbert
E. Lack of Vitamin A

My thoughts: So it looks to be elevation of Conjugated bilirubin, but no obstruction as an answer choice? Dubin Johnson/Rotor isn't in the FOILS nor is 2ndary biliary cirrhosis? So I have officially no clue

#2. 38 year old male attempts to commit suicide by turning his car on in his garage. Neuronal damage will be found in:

A. Amygdala
B. Globus Pallidus
C. Hypoglossal nucleus
D. Red Nucleus
E. Ventral posterior lateral thalamic nucleus.

My thoughts: ummm where is hippocampus?

#3. 26 year old Male presents with progressive anorexia and malaise of six months. A swelling is present in the left hypochondriac region that can be palpated as a firm mass under the left costal margin. He takes a deep breath and the swelling moves downward. The Organ most likely affected:

A. duodenum
B. Left Kidney
C. Liver
D. Pancreas
E. Spleen

My thoughts: migratory thrombophlebitis of pancreas?

#4. A 10 month old has been crying for several hours. Her mother states the infant hasn't had a bowel movement for several days, but her appetite had been normal until today. On physical examination the abdomen is distended and very tender. The most likely diagnosis is?

A. Hirschsprung
B. Intestinal adhesions
C. Intussusception
D. Meconium Ileus
E. Pyloric stenosis

My thoughts: intussusception?

 

[tk0102]

#2. 38 year old male attempts to commit suicide by turning his car on in his garage. Neuronal damage will be found in:

A. Amygdala
B. Globus Pallidus
C. Hypoglossal nucleus
D. Red Nucleus
E. Ventral posterior lateral thalamic nucleus.

My thoughts: ummm where is hippocampus?

Wow. Where did you get these questions?

The answer is B, for unclear reasons. But, out of those choices, maybe because it's in a watershed region?

http://www.ajronline.org/doi/full/10.2214/AJR.07.2425

 

[issey]

Wow. Where did you get these questions?

The answer is B, for unclear reasons. But, out of those choices, maybe because it's in a watershed region?

http://www.ajronline.org/doi/full/10.2214/AJR.07.2425

don't ask

 

[hardee17]

ABEC is what I would pick, awfully vague items. I think goljan touched on GP for CO poisoning.

 

[CaptainSSO]

ABEC is what I would pick, awfully vague items. I think goljan touched on GP for CO poisoning.

also what i would pick

for the first question, the ast>alt, which is a sign for alcoholic hepatitis. hemolysis would be indirect bilirubin, gastric ulcers have nothing to do w/ the question, gilbert would be unconjugated as well, and lack of vit. a would be more like night blindness/squamous metaplasia/keratitis

b. CO can affect globus pallidus, read that in medium robbins a long time ago. i wouldn't worry about that it's probably not ever going to come up. but now you know anyway

e. probably EBV mono w/ splenomegaly

c. hirschsprung and meconium ileus will both present w/in the first few days. hypertrophic pyloric stenosis within 3-6 wks i think. intestinal adhesions is more of an artifact of surgery IIRC, due to scar tissue formation

 

[Transposony]

Di George
Thymic Aplasia due to stress
Bruton agammaglobulinemia
Congenital hypogammaglobulinemia
lymphopenic agammaglobulinemia
Nezelofsyndrome
Transposition of the great vessels
Ebstein anomaly

Can anyone explain why the thymic shadow is absent in Bruton agammaglobulinemia since it is a B cell disorder and T-cell are actually increased in this condition?
I can understand why the lymphoid tissue like adenoids & peyers patches may be hypoplastic but why Thymus?
I looked up medscape where it does not mention that thymic shadow is absent.

The spleen, the tonsils, the adenoids, the Peyer patches in the intestines, and the peripheral lymph nodes may all be reduced in size or absent in individuals with X-linked agammaglobulinemia (XLA).

 

[issey]

Friends,

Comparing between tamponade vs pericarditis. Is it safe to say that since BOTH can have JVD, that the way you distinguish between the two based on lab values is hypotension and distant heart sounds in tamponade? Perhaps also electrical alterans ?

 

[TheSeanieB]

Does exercise have any effect on urine pH and drug clearance?

 

[cage92]

i know betablocker are contraindicated in mechanism since it block symp symptoms of hypoglycemia? but diabetic patient are hyperglycemic and other issue it is al contraindicated since it block hepatic gluconeoogeneis why i need gluconeogenesis in diabetic( since metformin treatmennt block gluconeogenes)

 

[Myxedema]

Friends,

Comparing between tamponade vs pericarditis. Is it safe to say that since BOTH can have JVD, that the way you distinguish between the two based on lab values is hypotension and distant heart sounds in tamponade? Perhaps also electrical alterans ?

An excellent question, which requires a good understanding of the terms themselves:

- Pericarditis: Inflammation of the pericardium. Because of this inflammation, serous/pus fluid can fill between the layers of pericardium, which is named as pericardial effusion. Thus, pericarditis can create pericardial effusion, which can enlarge the pericardial sac.
- Enlargement of pericardial sac: Like I've mentioned above, pericardial effusion can enlarge the pericardial sac, but that is not the only cause. Blood may also fill this sac and enlarge it (hemopericardium), caused by conditions such as aortic dissection.
- Cardiac tamponade: So far, we've talked about enlargement of the pericardial sac. This enlargement can take place over a relatively long period time, which would not compromise the cardiac function. However, if this enlargement of pericardial sac takes place over a short period of time, even a relatively smaller enlargement can restrict cardiac filling, which produces cardiac tamponade.

In short, enlargement of perdicardial sac, which may or may not be due to pericardial effusion created by pericarditis, can result in cardiac tamponade if it happens too quickly.

So why discuss all this? I hope by now it's clear that pericarditis can cause cardiac tamponade, so "pericarditis vs. tamponade" is not really an applicable concept. It is important to differentiate between a patient with or without cardiac tamponade, as this condition is rapidly fatal.

A patient with pericarditis, but without tamponade:

A 42-year-old woman who has a history of RA presents to the outpatient cardiology clinic with a new onset of chest pain. Upon questioning, she say that her chest pain occurs "in the middle", gets better when she sits up. She says the pain is not associated with exertion, and over-the-counter antacid tablets provided no relief. Cardiac examination reveals a continuous rubbing sound heard all over the precordium. Her vital signs are within normal limits. EKG shows elevation in all ST leads with PR depression. Suspecting pericarditis, transthoracic echocardiography is ordered, which shows roughly 500 mL of fluid accumulated in the pericardial sac.

A patient with tamponade

A 37-year-old man is brought to the emergency department after being stabbed in the chest following a bar fight. The patient is unconscious and cannot be aroused. History obtained from the paramedics in non-contributory. A pertinent physical examination shows a penetrating wound in the left 4th intercostal space near the precordium. Cardiac auscultation reveals distant heart sounds*. In addition, the patient's jugular veins are distended*. Vital signs are: T: 37,3C, BP: 90/60 mm Hg*, P: 129/min. You notice that the patient's blood pressure fluctuates with inspiration. One such measurement shows a BP of 78/57 mm Hg**. EKG shows alternating heights of QRS complexes with every beat***. A clinical diagnosis of cardiac tamponade is given, and emergent echocardiography immediately followed by pericardiocentesis is performed. Echocardiography shows the accumulation of blood and confirms the diagnosis of hemopericardium with cardiac tamponade.

- Things marked with (*) are Beck's triad, which is seen in tamponade: (1) Distant heart sounds, (2) Distended jugular veins, (3) Hypotension.
- Pulsus paradoxus, which is >= 10 fall in BP with inspiration and marked with (**), is a strong indicator of cardiac tamponade.
- Electrical alternans is another feature of cardiac tamponade, and is marked with (***).

Compare these with the previous patient: Heart sounds were not distant, but there was a friction rub. Jugular veins were not distended. Her vital signs were normal, there was no hypotension. Pulsus paradoxus wasn't present. And instead of electrical alternans, ST elevation in all leads with PR depression was seen.

 

[TheSeanieB]

Does anyone understand why mirtazapine causes sedation when it is an alpha-2 blocker, increasing NE and seratonin?

 

[Pinkleton]

Does anyone understand why mirtazapine causes sedation when it is an alpha-2 blocker, increasing NE and seratonin?

I believe it is a strong antihistamine. The sedation goes away after a few weeks

 

[donaldduck]

hey guys kinda of weird question that i couldn't seem find online anywhere, but how does our immune system kill cells that are infected HIV? Do we make antibodies to structural components or do CTL's do the job?

 

[loveoforganic2]

hey guys kinda of weird question that i couldn't seem find online anywhere, but how does our immune system kill cells that are infected HIV? Do we make antibodies to structural components or do CTL's do the job?

We do make antibodies (this is the basis of diagnosis), but this wouldn't be the mechanism of attack of infected cells. I would assume it'd be CTL's and NK cells

 

[hardee17]

What happens to the Hb curve from an individual who is acclimatized to high altitude and then descends to sea level? Anyone ever encounter this?

 

[loveoforganic2]

What happens to the Hb curve from an individual who is acclimatized to high altitude and then descends to sea level? Anyone ever encounter this?

I would imagine nothing at first, with it slowly returning to how it normally would be at sea level (left shifted) as 2,3-BPG synthesis was decreased. The only thing you're changing by moving to sea level is PAO2

 

[wanderer]

hey guys kinda of weird question that i couldn't seem find online anywhere, but how does our immune system kill cells that are infected HIV? Do we make antibodies to structural components or do CTL's do the job?

I believe the CD4 cells undergo apoptosis, so that the main effector cells would be CTLs and possibly NK cells.
Remember it's a virus so intracellular proteins would be presented complexed to MHC-I. And there's the potential for the NK pathway as well - not sure if this happens - edit - see here: https://en.wikipedia.org/wiki/Natural_killer_cell#Innate_resistance_to_HIV.3F

 

[loveoforganic2]

What accounts for the existence of the physiologic 5-15 mmHg A-a gradient? I think a UW question said it was mixing with bronchial vein blood, but I'm pretty sure those drain into the right atrium

 

[Transposony]

What accounts for the existence of the physiologic 5-15 mmHg A-a gradient? I think a UW question said it was mixing with bronchial vein blood, but I'm pretty sure those drain into the right atrium

Bronchial veins

The bronchial veins are small vessels that return blood from the larger bronchi and structures at the roots of the lungs. The right side drains into the azygos vein, while the left side drains into the left superior intercostal vein or the accessory hemiazygos vein.

The bronchial veins are counterparts to the bronchial arteries; however they only carry ~13% of the blood flow of the bronchial arteries.[1] The remaining blood is returned to the heart via the pulmonary veins.[1]

 

[loveoforganic2]

Bronchial veins

edit: Woops nvm, misread the last part. Thanks. I had read that wiki page and made the same misreading error. So the majority of the bronchial arteries drain into the pulmonary vv. if I'm reading that correctly?

 

[Transposony]

edit: Woops nvm, misread the last part. Thanks. I had read that wiki page and made the same misreading error. So the majority of the bronchial arteries drain into the pulmonary vv. if I'm reading that correctly?

No, the majority of blood from bronchial arteries drain into the central venous system (and therefore right atrium). however, a small percentage (~13%) of blood from bronchial arteries via bronchial veins (and also Thebesian veins) drains into the pulmonary veins (and therefore left atrium).

It's not explained very well @ Wikipedia.

Here is a better description:

The origin and distribution of the bronchial vasculature vary considerably between and among species both at the macro- and microvascular level. Bronchial vessels usually originate from the aorta or intercostal arteries, entering the lung at the hilum, branching at the mainstem bronchus to supply the lower trachea, extrapulmonary airways, and supporting structures; this fraction of the bronchial vasculature drains into the right heart via systemic veins. Bronchial vessels also supply the intrapulmonary airways as far as the level of the terminal bronchioles where they form extensive anastomoses with the pulmonary vasculature; this systemic-to-pulmonary blood drains via pulmonary veins to the left heart.

Here is a very good diagram explaining it all.

 

[loveoforganic2]

That helped a bunch, thank you!

 

[ChessMaster3000]

Hey everyone, does anyone know the pathophys behind the fact that children with atrial septal defects have a tendency towards recurrent respiratory traft infections?

 

[skyblue2000]

Can anyone exam question 80 in UW? I keep reading this question but I can't seem to understand why HIDA is better than an ultrasound? Is it just comparing acalculous to calculous reasons... And that HIDA can detect both whereas ultrasound can only do calculous?

 

[JP2740]

i know betablocker are contraindicated in mechanism since it block symp symptoms of hypoglycemia? but diabetic patient are hyperglycemic and other issue it is al contraindicated since it block hepatic gluconeoogeneis why i need gluconeogenesis in diabetic( since metformin treatmennt block gluconeogenes)

Hypoglycemia is an adverse effect of diabetic medications. Diabetics usually are alerted to this by the symptoms they experience.