HY lecture notes:

32M + pneumothorax that does not resolve following placement of a chest tube; Dx? –> ruptured bronchus or rupture of intrathoracic trachea.

32M + pneumothorax with a persistent air leak despite chest tube placement; Dx? –> ruptured bronchus or rupture of intrathoracic trachea.

32M + contralateral tracheal deviation + low BP; Dx? –> tension pneumothorax; Tx = needle decompression followed by chest tube. If out in the field (i.e., not in hospital), if there is penetrating chest trauma, tape over the wound on three sides only, so air can exit but not enter. Tension pneumothorax need not be associated with penetrating chest trauma, but this is one of the most common etiologies.

Mechanism of low BP in tension pneumothorax? –> answer = compression of venous structures (IVC).

25M + tall +/- uses cocaine + has dyspnea + air in pleural space; mechanism? –> rupture of subapical bleb causing spontaneous pneumothorax; Tx = can technically observe if very small and patient stable; however answer on USMLE will still be needle decompression followed by chest tube.

35F + C-section 24-48 hours ago + crackles at both lung bases; Dx? –> atelectasis; normally the fever is within 24 hours, but a Q on one of the forms says “two days after surgery.”

48M + motor vehicle accident (MVA) + rib fractures + paradoxical breathing (i.e., chest wall moves outward with exhalation and inward with inhalation); Dx? –> flail chest.

48M + MVA + has severe pain and/or bruising over the sternum; Dx? –> myocardial contusion –> do an ECG + monitor in hospital due to high risk of arrhythmia. Get troponins.

This is where things get hard for the surg shelf:

48M + MVA + rib fractures + underlying infiltrates + no other info given in the stem; Dx? –> pulmonary contusion. The Q will not say “white-out of the lung” –> too easy / buzzwordy of a description.

48M + MVA + no rib fractures + lobar infiltrates + no other info given in the stem; Dx? –> pulmonary contusion –> need not have rib fractures for pulmonary contusion.

48M + MVA +/- rib fractures + O2 sats decrease when 2L of fluid is given; Dx? –> pulmonary contusion –> contused lung is very fluid sensitive.

48M + MVA +/- rib fractures + severe pain/bruising over the sternum + O2 sats decrease when 2L of fluid is given; Dx? –> myocardial contusion, not pulmonary contusion –> weird, because the stem said the O2 sats decreased with fluid, but the pain/bruising over the sternum “wins.”

Pulmonary contusion isn’t a diagnosis of exclusion per se, but I’ve noticed across NBME Qs that the presentation is fairly non-specific.

Essentially:

Is there paradoxical breathing? Yes? Ok, flail chest. No? Ok, not flail chest.

Do they mention a persistent air leak despite a chest tube? Yes? Ok, ruptured bronchus. No? Ok, not ruptured bronchus.

Do they say bruising/pain over the sternum? Yes, Ok, myocardial contusion. No? Ok, not myocardial contusion.

Do they say pulmonary infiltrates on CXR in the setting of trauma and I’ve eliminated the above three Dx? Yes? Ok, pulmonary contusion is likely answer.

HY lecture notes:

Short clip, but some hard transfusion concepts, so the brevity is warranted.

—

Antiphospholipid syndrome (APS) will normally present as in vivo thromboses despite in vitro increase in aPTT. This paradoxical presentation is how you make the Dx.

Phospholipid is needed for the in vitro aPTT test to run, so if there are Abs against it, then the test is prolonged (i.e., it cannot run as smoothly). However antibodies against phospholipid will also cause platelet clumping intravascularly, resulting in thrombotic events.

Antiphospholipid syndrome can be caused by different types of antibodies, such as anti-beta-2-microglobulin or anti-cardiolipin. If the disease occurs in SLE, then the antibodies are simply called “lupus anticoagulant.”

Antiphospholipid syndrome is a notable cause of recurrent miscarriage due to thromboses in placental vasculature (uteroplacental insufficiency).

Patients with APS can have a false (+) VDRL, the serological screening test for syphilis (secondary and later).

Where things get hard for Surg shelf:

There’s a Q on one of the forms where they give you a 22-year-old male with thromboses. They give you no other information. Answer is antithrombin III deficiency. APS is also listed but is wrong.

AT III deficiency normally presents in patients with chronic nephrotic syndrome (e.g., diabetic glomerulonephropathy) who lose AT III in the urine, often leading to renal vein thromboses. But AT III deficiency can also be an inherited condition.

In order to make the contrast, presumably the question will tell you that aPTT is elevated (normal 25-40 seconds) if they want APS.

If they don’t mention aPTT elevation, APS will be the answer if they mention (as discussed above):

• Recurrent miscarriage and/or
• Patient who has lupus and/or
• False (+) VDRL.

HY lecture notes:

Pathologic jaundice in peds = must have at least one of the following:

1. Any jaundice on the first day of life (first 24 hours of life), period = pathologic.
2. Jaundice present after one week if term, or after two weeks if preterm = pathologic.
3. Total bilirubin >15 mg/dL.
4. Direct bilirubin >10% of total bilirubin, even if total bilirubin is <15 mg/dL.
5. Rate of change of increase in bilirubin >0.5 mg/dL/hour.

Biliary atresia in neonates shows up on surgery shelves, as with the above student on one of the practice forms. In turn there is some overlap with pediatric shelf for this diagnosis and management.

The standard vignette is a neonate who has total bilirubin of, e.g., 14 mg/dL, with a conjugated (direct) bilirubin of 12 mg/dL.

So at first you’re like, “I don’t get it though. The total bilirubin is normal.” Yes, but the direct bilirubin is >10% of total, so it’s still pathologic jaundice.

Surg shelf wants “liver biopsy” as the next best step in management.

If they ask for treatment, go straight to “liver transplant.”

If neonate has pathologic jaundice (not due to biliary atresia) and they ask for treatment, choose “phototherapy” first, followed by “exchange transfusion” if they tell you they already tried phototherapy to no avail.

Breastmilk jaundice vs breastfeeding jaundice:

Breastmilk jaundice = due to beta-glucuronidase in breast milk, which leads to de-conjugation of intestinal bilirubin + increased enterohepatic circulation –> jaundice that starts on day 3-5 and peaks at 2-3 weeks –> Tx = stop breastfeeding for ~48 hours (and do bottle feeding), which leads to a rapid decrease in bilirubin; once breastfeeding is resumed, bilirubin might rise, but not back to pathologic levels.

Breastfeeding jaundice = insufficient feeding (e.g., failure of suckling, etc.) + decreased milk intake leads to reduced intestinal clearance of bilirubin –> increased enterohepatic circulation –> jaundice that peaks at 3-5 days –> Tx = formula feeding (fluid + caloric supplementation).

Physiologic jaundice is the answer if all bilirubin parameters are in the normal range. So they can say in the vignette that the neonate is slightly jaundiced and is attaching to the breast poorly during feeds, but if all of the bilirubin parameters are in the normal range, the answer is physiologic jaundice, not breastfeeding jaundice.

HY lecture notes:

How does isolated left heart failure present? → fluid in the lungs (pulmonary edema) +/- pleural effusion; orthopnea, paroxysmal nocturnal dyspnea (PND); depending on the etiology of the heart failure, the structure of the heart will take on different characteristics, but the important point about LH failure is fluid in the lungs → also really important you know that pulmonary capillary wedge pressure (PCWP) is increased in any LH pathology (even if the pressure is within the acceptable range prior to full-blown LH decompensation, the PCWP is still increased relative to the patient’s original baseline in LH pathology.

What is PCWP? → equal to left atrial pressure; if you stick a catheter through the venous circulation all the way back to the right heart, and then into the pulmonary circulation, and then into a distal pulmonary capillary such that it can’t go any farther, the pressure reverberations are said to best reflect those of the left atrium. The USMLE is obsessed with PCWP; you need to know it is increased not just in cardiogenic shock, but also in LH pathology as I’ve stated above.

High PCWP occurs if there is any left heart pathology. Not just in cardiogenic shock, but also in mitral stenosis (increased afterload on LA → so more pressure in LA → higher PCWP) or mitral regurg (higher preload in LA → higher pressure → higher PCWP), as well as any cause of left ventricular hypertrophy (if the LV is experiencing a pressure or volume overload, that effect will back up to the LA).

In aortic stenosis → higher afterload on LV (concentric hypertrophy) → therefore higher afterload on LA → higher PCWP.

In aortic regurg → higher preload on LV (eccentric hypertrophy) → therefore higher preload on LA → higher PCWP.

It should also be noted that it is very rarely stated that the left atrium “hypertrophies”; the LV will hypertrophy; the LA will dilate. Any pathology at the level of the mitral valve or later (LV, aortic valve, or aorta) will cause left atrial dilatation and increased PCWP.

Most pleural effusions are due to either congestive heart failure (CHF) or malignancy.

CHF = left heart failure + right heart failure.

The most common cause of right heart failure is left heart failure.

Therefore in CHF, PCWP is high → this increased pulmonary pressure leads to pulmonary hypertension (where there is actual hypertrophy of the tunica media of the pulmonary arteries) → backs up to the RV → right heart failure.

So let’s say you’ve got fluid in the lungs, but they say PCWP is normal → that means the fluid in the lungs can’t be due to left-heart origin because, if it were, PCWP would have to be high.

ARDS (acute respiratory distress syndrome) presents with normal PCWP. ARDS is when proteinaceous fluid leaks out into the alveoli bilaterally and is frequently due to sepsis, trauma, or pancreatitis. So USMLE Qs like to say, e.g., 50M alcoholic with abdo pain gets dyspnea with bilateral infiltrates + his PCWP is normal → Dx = ARDS.

In ARDS, pO2/FiO2 must be less than 300. It is treated with low-tidal-volume mechanical ventilation (prevents barotrauma) + permissive hypercapnia (we allow CO2 to be slightly elevated [>44 mmHg] to prevent barotrauma).

For cor pulmonale, probably the most important piece of info regarding this condition is that PCWP is normal, which tells you the cause of the RH failure cannot be from LH origin. For instance, if you have a guy with COPD who also has heart disease, if his PCWP is elevated, then we cannot conclude that his right heart failure is a result of the lung disease in isolation because increased PCWP can lead to RH failure.

—

Hypovolemic shock: low VR, low CO, high TPR, low PCWP

Distributive shock (anaphylactic, septic, neurogenic): high VR, high CO, low TPR, normal PCWP

Cardiogenic shock: low VR, low CO, high TPR, high PCWP

HY lecture notes:

87F + coffee bean sign on AXR + obstipated; Dx? → sigmoid volvulus.

Tx for sigmoid volvulus? → answer on surgery NBME = “sigmoidoscopy-guided placement of rectal tube.”

How do you Dx congenital midgut volvulus? → upper-GI series (AXR + contrast follow-through of esophagus, stomach, and duodenum with barium or gastrografin).

Where do most colonic ischemic ulcers occur? → watershed areas → splenic flexure (watershed of SMA and IMA) + sigmoidal-rectal junction (watershed of IMA and hypogastric artery).

72M + advanced CVD + bloody stool; Dx? → ischemic colitis (due to ischemic ulcer).

79M + Hx of atrial fibrillation + severe, acute, diffuse abdo pain; Dx? → acute mesenteric ischemia caused by mural thrombus embolizing to SMA or IMA.

Above 79M; next best step in Mx? → mesenteric arteriography.

Above 79M; Tx? → antibiotics (for necrotic bowel) then laparotomy (to remove necrotic bowel) → they will tell you in last line of vignette that IV Abx are administered and then ask for the next step, which is just laparotomy. It should be noted that the literature mentions various Txs like embolectomy, but the USMLE wants resection of nonviable bowel as the answer.

52F + short episode of ventricular fibrillation + defibrillated + now has severe abdo pain; Dx? → acute mesenteric ischemia due to ischemia caused by VF, not an embolus → antibiotics; CT if stable; if unstable go straight to laparotomy.

55F diabetic + Hx of intermittent claudication + Hx of abdo pain 1-2 hours after eating meals; Dx? → chronic mesenteric ischemia (CMI) caused by severe atherosclerosis of SMA or IMA (essentially angina of the bowel).

55F diabetic + Hx of CABG + Hx of abdo pain 1-2 hours after eating meals; next best step in Dx? → mesenteric arteriography (CMI).

55F diabetic + Hx renal artery stenosis + Hx of abdo pain 1-2 hours after eating meals; Tx? → angioplasty + stenting (CMI) to restore blood flow.

Patient with CMI who has a 2-day Hx of severe abdo pain + fever; Dx? → acute mesenteric ischemia (acute on chronic due to a thrombosis; essentially akin to an “MI” of the bowel) → do mesenteric arteriography to Dx; Tx with Abx + laparotomy to remove necrotic bowel.

69M + LLQ pain + fever = diverticulitis → Dx with CT with contrast of abdomen → Tx w/ Abx (metronidazole, PLUS fluoroquinolone or Augmentin; USMLE won’t ask you the exact Abx, but you should be aware that metro covers anaerobes below the diaphragm) → never do a colonoscopy on someone with suspected diverticulitis, as you may cause perforation. However, after the diverticulitis is fully treated + cleared, patient will need a follow-up colonoscopy to rule out malignancy.

C diff + fever of 104F + tachy + diffuse abdominal pain; next best step in Mx? → AXR → look for toxic megacolon → Tx w/ NPO (nothing by mouth), NG decompression + rectal tube (decompression) + Abx (vancomycin or fidaxomicin) + steroids (if UC) + correct any electrolyte imbalances (sometimes low K) → if patient doesn’t improve with conservative therapy, must do surgery (subtotal colectomy + ileostomy); do not do a colonoscopy on a patient with toxic megacolon as this will cause perforation.

HY lecture notes:

Recurrent bouts of acute pancreatitis cause chronic pancreatitis –> pancreatic enzymes will usually be normal on the NBME/USMLE because of exocrine pancreas burn out – i.e., recurrent tissue damage leads to defective enzyme secretion. Patients need pancreatic enzyme replacement as the Tx.

Patients with chronic pancreatitis will present with steatorrhea because of decreased lipase secretion –> impaired fat absorption –> can also lead to fat-soluble vitamin deficiencies.

On one of the IM or Surg forms, they have “pancrelipase” as the answer.

44M + fasting glucose of 112 mg/dL + dark skin on forearms + arthritis; Dx? –> hereditary hemochromatosis –> AR, chromosome 6, HFE gene, C282Y or H63D missense mutations account for 90% –> “Bronze diabetes” –> hyperpigmentation (from hemosiderin deposition) + diabetes due to iron deposition in tail of pancreas (normal fasting glucose is 72-99 mg/dL; impaired fasting glucose [pre-diabetic] is 100-125 mg/dL; diabetic is two fasting glucoses 126 or greater, or a single HbA1c >6.5%, or any random glucose >200 mg/dL) + third finding such as arthritis, cardiomyopathy, or infertility.

44M + fasting glucose of 130 mg/dL + hands are sore + x-ray of hands shows DIP involvement; what’s the Dx for the type of arthritis? –> answer = pseudogout, not osteoarthritis. Student says wtf? The two most common etiologies for pseudogout are hemochromatosis and primary hyperparathyroidism (pseudogout is calcium pyrophosphate deposition disease, and will present as either a monoarthritis of a large joint such as the knee, or as an osteoarthritis-like presentation of the hands.

Tx of hereditary hemochromatosis –> serial phlebotomy, not chelation therapy.

44M patient above + USMLE asks what’s the mechanism for his disease –> answer = “increased intestinal absorption of iron.”

44M above + next best step in Dx? –> check serum ferritin (>300 ug/L in men + post-menopausal women; or >200 in premenopausal women; USMLE will always say >300 so don’t worry).

Why do men get hemochromatosis younger + with worse Sx than women? –> menstruation slows progression of disease.

What is secondary hemochromatosis? –> aka transfusional siderosis (amazing to remember if you want to sound sophisticated) –> due to chronic blood transfusions –> each transfusion of RBCs contains iron –> seen classically in beta-thalassemia major or any other patients receiving ongoing transfusions.

Tx for secondary hemochromatosis (transfusional siderosis) –> chelation therapy (e.g., deferoxamine), not serial phlebotomy.

Blind loop syndrome

Normally bacterial growth in small bowel is limited by peristalsis + normal flow of digestive contents. In the case of physical or peristaltic disruption, bacterial overgrowth in the small bowel may ensue, leading to diarrhea and malabsorption. Blind loop syndrome may be seen in the setting of surgery, strictures, fistulae, achlorhydria. Treatment is with doxycycline or rifaximin.

Dumping syndrome

In the setting of roux-en-y procedure (gastric bypass), hyperosmolar chyme from the stomach may enter the duodenum too quickly, leading to a spike in insulin secretion and hypoglycemia. This also can be accompanied by diarrhea. On the USMLE: gastric bypass Hx + hypoglycemia + diarrhea = Dumping syndrome.

Pseudomembranous colitis

For C. difficile, choose “ingestion of spores” as the etiology, not “bacterial overgrowth.” The latter refers to Blind loop syndrome.

Patient takes Abx for several days + has watery diarrhea; Dx? –> difficile (pseudomembranous colitis).

Patient takes Abx for several days + has crampy LLQ pain + bloody diarrhea; Dx? –> difficile à this is on a 2CK NBME –> Yersinia enterocolitica was also listed and was wrong; this is a good distractor because Y. enterocolitica causes pseudoappendicitis due to ileitis / mesenteric adenitis, but is RLQ pain, not LLQ.

Which Abx cause C. diff overgrowth? –> clindamycin, cephalosporins, ampicillin are highest yield.

Dx of C. difficile? –> answer = stool AB toxin test, not stool culture (exceedingly HY).

Tx of C. difficile? –> guidelines as of Feb 2018 say oral vancomycin first-line, not metronidazole –> apparently UW is updated on this too now –> note that vanc is given orally –> apart from C. diff, it’s always given IV because it has terrible oral bioavailability, but in the case of C. diff, where we want the drug confined to the lumen of the colon, that makes sense.

Mechanism of colonic necrosis in C. diff colonic necrosis? –> answer = “cytoskeletal disruption.”

Patient is treated with vanc for C. diff but gets recurrence weeks later; why? –> answer = “regermination of spores.”

C. diff + fever of 104F + tachy + diffuse abdominal pain; next best step in Mx? –> AXR –> look for toxic megacolon –> Tx w/ NPO (nothing by mouth), NG decompression + rectal tube (decompression) + Abx (vancomycin or fidaxomicin) + steroids (if UC) + correct any electrolyte imbalances (sometimes low K) –> if patient doesn’t improve with conservative therapy, must do surgery (subtotal colectomy + ileostomy); do not do a colonoscopy on a patient with toxic megacolon as this will cause perforation.

HY lecture notes:

Person who’s vomiting; what’s the biochemical disturbance? –> hypokalemic hypochloremic metabolic alkalosis –> low K, low Cl, high pH, high bicarb, low H, anion gap normal (even though it’s alkalosis, not acidosis, the USMLE will still ask an arrow for the anion gap here).

2-week-old male + forceful non-bilious vomiting; Dx? –> hypertrophic pyloric stenosis.

Dx of pyloric stenosis? –> abdominal ultrasound to show olive-shaped hypertrophied pylorus.

Tx of pyloric stenosis? –> myomectomy.

Who gets pyloric stenosis? –> first-born males (weird, but it’s on an old NBME) + neonates taking oral erythromycin for chlamydial ophthalmia neonatorum (erythromycin is a motilin-receptor agonist).

2-week-old male + bilious vomiting; Dx? –> duodenal atresia, annular pancreas, congenital midgut volvulus, or Hirschsprung (correct, Hirschsprung can present with bilious vomiting).

2-week-old + Down syndrome + bilious vomiting + passed meconium ok; Dx? –> duodenal atresia.

2-week-old + Down syndrome + bilious vomiting + slow to pass meconium; Dx? –> Hirschsprung.

How do you Dx duodenal atresia? –> abdominal x-ray (AXR) showing double-bubble sign (very HY).

2- week-old + bilious vomiting + triple bubble sign; Dx? –> jejunal atresia.

How do you Dx Hirschsprung? –> rectal manometry, followed by confirmatory rectal biopsy showing absence of ganglion cells.

Mechanism for Hirschsprung? –> failure of migration of neural crest cells distally to the rectum.

How do you Dx congenital midgut volvulus? –> upper-GI series (AXR + contrast follow-through of esophagus, stomach, and duodenum with barium or gastrografin).

Failure to pass meconium at birth. Most likely cause overall? –> cystic fibrosis.

18-month-old + intermittent abdominal pain + crying + blood in stool; Dx? –> intussusception.

18-month-old + intermittent squatting + crying + FOBT positive; Dx? –> intussusception.

18-month-old + occasionally brings legs to chest + vomits + FOBT positive; Dx? –> intussusception.

18-month-old + occasionally brings legs to chest + vomits + FOBT negative; Dx? –> volvulus –> this is congenital midgut volvulus.

Presentation sounds like intussusception but no blood per rectum –> answer = congenital midgut volvulus.

Cause of intussusception? –> >99% are in kids under age 2; caused by lymphoid hyperplasia due to viral infection (e.g., rotavirus) or recent vaccination; if in adult (usually elderly), it is caused by colorectal cancer.

Dx and Tx of intussusception? –> USMLE wants enema as the answer. Even though ultrasound can be done which shows a target sign, the USMLE always wants enema. And it can be any type. I’ve seen “air contrast enema”, “air enema,” “contrast enema,” all as answers. I also had a student simply get “water-soluble contrast enema” on the exam, which means gastrografin. Barium would refer to regular contrast.

HY lecture notes:

Random point for pediatrics is that pregnancy can occur before one’s first period, so if they give you, e.g., a 13F who’s never had a menstrual period but who presents with signs and symptoms suggestive of pregnancy (i.e., nausea/vomiting, suprapubic mass, etc.), consider pregnancy as an answer. One of the pediatric forms has a Q where the answer was “beta-hCG” in this scenario.

HY is differentiating polycystic ovarian syndrome (PCOS) from hypothyroidism from Cushing syndrome. This applies to pediatrics as well and there are many questions on it.

High BMI female + irregular menstrual cycles –> anovulation.

Anovulation + hirsutism –> PCOS.

Anovulation. Cause USMLE wants? –> insulin resistance –> causes abnormal GnRH pulsation.

Why hirsutism in anovulation –> abnormal GnRH pulsation causes high LH/FSH ratio.

Why high LH/FSH ratio important in anovulation/PCOS –> ovulation stimulated when follicle not ready –> no ovulation (anovulation) –> follicle retained as cyst.

What’s LH do? –> Stimulates theca interna cells (females) and Leydig cells (males) to make androgens.

What’s FSH do? –> Stimulates granulosa cells (females) and Sertoli cells (males) to make aromatase; also primes follicles.

Tx for PCOS –> if high BMI, weight loss first always on USMLE.

Tx for PCOS if they ask for meds and/or weight loss already tried –> OCPs (if not wanting pregnancy); clomiphene (if wanting pregnancy).

PCOS increases risk of what –> endometrial cancer (unopposed estrogen).

PCOS will present on the USMLEs + various shelf exams as missed periods, not gradually prolonged periods. The cysts are the result of follicles that literally did not rupture, meaning ovulation does not occur.

14F + low mood + gradually increasing fatigue + menstrual cycles gradually increasing in length + BMI 26; Dx? –> hypothyroidism (Hashimoto).

16F + proximal muscle weakness + increased creatine kinase + low mood + fatigue; Dx? –> Hashimoto.

15MM + decreased ability to get up from chair unassisted + HR 60; Dx? –> Hashimoto.

17M + total cholesterol 300 mg/dL + high hepatic AST + HR 55; Dx? –> Hashimoto (hypothyroidism can cause bradycardia, high cholesterol, and high AST [the latter is weird, correct]).

Hashimoto parameters –> high TSH, low T3, low T4, decreased iodine uptake

Mechanism for Hashimoto –> antibodies against thyroperoxidase + thyroglobulin; anti-microsomal.

Histo of Hashimoto –> lymphocytic infiltrate (asked on one of the 2CK NBME forms weirdly enough).

Tx for Hashimoto = levothyroxine (synthetic T4).

Key point regarding menstruations is that periods gradually increase in length + become heavier;  although hypothyroidism and PCOS can present with amenorrhea, PCOS won’t present with gradually increasing length + heaviness the same way hypothyroidism will.

Cushing disease Qs can present with either increased length of menstrual cycle + heaviness of periods, or missed periods altogether (insulin resistance –> anovulation/PCOS). However you’ll be able to differentiate in the vignette because they’ll throw in other signs of Cushing like purple striae.

One Cushing Q on a 2CK form gave just gradually increasing heaviness of periods + acanthosis nigricans –> the reason the answer wasn’t PCOS is because, once again, we’d expect missed periods with PCOS.

It is suspected that the mechanism for menstrual dysfunction in hypothyroidism is as follows: low T3/T4 –> decreased negative feedback at hypothalamus –> increased TRH –> increased prolactin release –> GnRH dysfunction. It should be noted that prolactin is regulated two ways: 1) dopamine inhibits prolactin release, and 2) TRH (not TSH) directly stimulates it.

Should also be noted that Cushing disease in children can present as precocious puberty and/or stunted growth, rather than as Cushingoid appearance.

HY lecture notes:

Two main types of hemolytic disease of the newborn:

1. Rhesus factor (-) type
2. ABO type

Rh (-) type:

Always a mother in second pregnancy or later. Never in first pregnancy.

Mom who is Rh (-) does not have Rh antigen on her RBCs, nor does she have antibodies against Rh antigen.

If the father of the fetus is Rh (+), there is a high chance the fetus is also Rh (+).

During parturition, if there is mixing of the fetal and maternal blood (i.e., during traumatic labor), the mother’s immune system will recognize the Rh antigen on the fetal RBCs as foreign, and in turn will develop IgM (and then later IgG) antibodies against it.

In subsequent pregnancies, the mother’s IgG against Rh factor will cross the placenta and attack the fetal RBCs that have Rh on the surface (assuming Rh + fetus).

This results in hemolysis in the fetus of varying severities. The fetus may become severely anemic in utero, requiring transuterine blood transfusions, or may experience pathologic jaundice following birth.

Maternal Rh status must be assessed during first pregnancy.

For second pregnancies-onward:

At 28 weeks gestation + prior to labor, the Rh (-) mom will receive RhoGAM to prevent her immune system from creating antibodies against Rh just in case there is mixing of her blood with the fetus’s. RhoGAM refers to Rh immunoglobulin that will bind to and mop up any antigen that has entered her circulation.

RhoGAM is not just given at 28 weeks + at parturition, but it is also administered to women who undergo any form of instrumentation (i.e., chorionic villus sampling, amniocentesis, etc.), or who experience spontaneous abortion, or procedural abortion, or abruptio placentae.

The USMLE wants you to know that you do indirect Coomb’s test at the first trimester checkup. This will take the mother’s serum, mix it with laboratory Rh (+) RBCS, and see if there’s agglutination. If there’s agglutination, this says the mother has developed antibodies against Rh antigen from the prior pregnancy and will NOT go on to receive RhoGAM later in pregnancy. In other words, if she’s already made antibodies against Rh antigen, it’s too late to give her RhoGAM because it won’t change anything.

ABO type:

USMLE will usually give you an O+ mom in her first pregnancy, and they will say the fetus is either A or B blood type.

Antibodies we normally produce against opposing blood types (e.g., person with B blood has antibodies against A blood) are IgM and do not cross the placenta.

However patients with O blood will have a fraction of their antibodies that are IgG and can cross the placenta.

This means a mother who is O blood, in her first pregnancy, can have a fetus who experiences in utero hemolysis, or a neonate who experiences hemolytic disease of the newborn. The fetus/neonate must be A or B blood type.

A couple high-yield points here:

1. ABO type hemolytic disease of the newborn can absolutely occur in a pregnancy where the mom is Rh negative. But the USMLE will always give you an Rh + mom because they want to assess that you even know what ABO type HDN is. In other words, the question writers are aware that some students might see Rh negative status, and without even understanding the mechanisms, guess the diagnosis of HDN correctly. So they want to weed out students who haven’t heard of ABO type HDN by giving you an Rh + mom.
2. ABO type hemolytic disease of the newborn can occur in any numbered pregnancy. The USMLE will usually give you a first pregnancy because the mother with O blood who has IgG antibodies had these antibodies prior to the first pregnancy.

Bottom line:

Rh (-) HDN = 2nd pregnancy onward in Rh – mom with Rh + fetus.

ABO HDN = 1st pregnancy in O mom with A or B fetus. Mom can be Rh – and in 2nd pregnancy onward, but USMLE will give you 1st pregnancy with an O+ mom.

HY lecture notes:

Pathologic jaundice in peds = must have at least one of the following:

1. Any jaundice on the first day of life (first 24 hours of life), period = pathologic.
2. Jaundice present after one week if term, or after two weeks if preterm = pathologic.
3. Total bilirubin >15 mg/dL.
4. Direct bilirubin >10% of total bilirubin, even if total bilirubin is <15 mg/dL.
5. Rate of change of increase in bilirubin >0.5 mg/dL/hour.

Most common vignette in peds regarding this stuff is biliary atresia.

They’ll give you a neonate who has a total bilirubin of, e.g., 13 mg/dL, with a direct (conjugated) bilirubin of 12 mg/dL.

At first you might be like, “Wait, but total bilirubin is fine isn’t it?” Yeah, but the direct bilirubin is >10% of total. Direct bilirubin should be under 1.3 mg/dL if this were physiologic jaundice.

When you get this type of vignette, choose “liver biopsy” as the next best step; if they ask for the treatment, go straight to “liver transplant.”

If neonate has pathologic jaundice (not due to biliary atresia) and they ask for treatment, choose “phototherapy” first, followed by “exchange transfusion” if they tell you they already tried phototherapy to no avail.

Breastmilk jaundice vs breastfeeding jaundice:

Breastmilk jaundice = due to beta-glucuronidase in breast milk, which leads to de-conjugation of intestinal bilirubin + increased enterohepatic circulation –> jaundice that starts on day 3-5 and peaks at 2-3 weeks –> Tx = stop breastfeeding for ~48 hours (and do bottle feeding), which leads to a rapid decrease in bilirubin; once breastfeeding is resumed, bilirubin might rise, but not back to pathologic levels.

Breastfeeding jaundice = insufficient feeding (e.g., failure of suckling, etc.) + decreased milk intake leads to reduced intestinal clearance of bilirubin –> increased enterohepatic circulation –> jaundice that peaks at 3-5 days –> Tx = formula feeding (fluid + caloric supplementation).

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Before even telling you what G6PD is or why it’s significant, you need to know this:

Ok cool. Now that that’s out of the way, the reason the USMLE gives a fuck about G6PD is because it’s used to generate NADPH.

Why is NADPH important? Because it’s production ultimately leads to the mopping up of free radicals and the neutralizing of oxidizing agents and H₂O₂.

Adding an extra piece of info, NADPH helps convert oxidized glutathione into reduced glutathione. The latter is a reducing agent that neutralizes oxidizing agents.

In turn, G6PD deficiency can lead to hemolysis secondary to oxidative stress.

Questions classically mention an African-American boy with decreased hematocrit after receiving a drug (e.g., dapsone, primaquine, sulfonamides).

But hemolysis can also occur with consumption of fava beans (favism).

The reduced lifespan of a bite cell RBC = ↑ RBC turnover = ↑ resistance to malaria.

The last factoid:

Pyruvate kinase is the last enzyme of glycolysis (PEP → pyruvate). ATP is produced in this step.

Pyruvate kinase deficiency → decreased ATP → decreased RBC Na/K ATPase activity → Na builds up inside RBC → RBC swelling + lysis.

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1. What is the inheritance pattern of G6PD deficiency?

 AR

 AD

 XR

 XD

G6PD deficiency is XR.

2. What kind of RBCs do you see on a blood smear in G6PD deficiency?

Degmacytes (bite cells)

3. What are Heinz bodies?

Heinz bodies are denatured/oxidized hemoglobin inside RBCs.

4. G6PD deficiency leads to decreased production of which critical molecule?

NADPH

5. Name three drugs that notably cause hemolysis in G6PD deficiency.

Dapsone, primaquine, sulfa drugs (various)

There are many drugs that can cause hemolysis in G6PD deficiency. I mention the above ones because of their high-yieldness on the USMLE.

6. What are the two most common causes of hemolytic anemia secondary to an enzyme deficiency?

G6PD deficiency (#1); Pyruvate kinase deficiency (#2)

7. Which of the following best describes G6PD deficiency? (Select all that apply)

 Decreased NADPH production

 Decreased NADP+ production

 Decreased -S-S- production

 Decreased -SH production

 Decreased oxidized glutathione

 Decreased reduced glutathione

G6PD deficiency directly leads to decreased NADPH production. This causes decreased ability to convert oxidized glutathione (-S-S-) to reduced glutathione (-SH), since NADPH is a reducing agent.

8. What food can precipitate G6PD crisis?

Fava beans

9. What would the bilirubin level be in someone with G6PD crisis?

>1.0 mg/DL; with an isolated increase in unconjugated bilirubin.

Normal bilirubin level is 1.0 mg/dL, with direct being 0.1 mg/dL. In the event of hemolysis, bilirubin will rise. The liver has a high capacity to handle bilirubin, so conjugated should not increase, even in the event of significant hemolysis. If conjugated rises, there is almost certainly an obstruction etiology.

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