Just to add: gonadal dysgenesis is "defective development of the gonads in an embryo, with reproductive tissue replaced with functionless, fibrous tissue, termed streak gonads" per wiki. This is common in Turner's syndrome. External genetalia are typically normal at birth.

Just to add: gonadal dysgenesis is "defective development of the gonads in an embryo, with reproductive tissue replaced with functionless, fibrous tissue, termed streak gonads" per wiki. This is common in Turner's syndrome. External genetalia are typically normal at birth.

My dumb ass thought ketonemia was like anemia of ketones or something and thus meant low ketones so I almost put fatty acid oxidation (hypoketotic hypoglycemia). FYI ketonemia is high ketones.

Defects in fatty acid oxidation would also be corrected with the sugar additions so even if you suck at medical vocab you could rule it out.

"Simple rules of the brainstem" (credit to our anatomy gods at UofL for organizing, also this image is fucking great for visual learners):

1. There are 4 structures always in the ‘midline‘ beginning with M
• Motor pathway (or corticospinal tract): damage results in contralateral weakness of the arm and leg
• Medial Lemniscus: damage results in contralateral loss of vibration and proprioception in the arm and leg
• Medial longitudinal fasciculus: damage results in ipsilateral inter-nuclear ophthalmoplegia (failure of adduction of the ipsilateral eye towards the nose and nystagmus in the opposite eye as it looks laterally)
• Motor nucleus and nerve: damage results in ipsilateral loss of the cranial nerve that is affected (III, IV, VI or XII)


2. There are 4 structures to the ‘side‘ (lateral) beginning with S
• Spinocerebellar pathway: damage results in ipsilateral ataxia of the arm and leg
• Spinothalamic pathway: damage results in contralateral alteration of pain and temperature affecting the arm, leg and rarely the trunk
• Sensory nucleus of CN V: damage results in ipsilateral alteration of pain and temperature on the face in the distribution of CN V (this nucleus is a long vertical structure that extends in the lateral aspect of the pons down into the medulla)
• Sympathetic pathway: damage results in ipsilateral Horner’s syndrome, that is partial ptosis and a small pupil (miosis)


3. The rule of CN 4’s (also found in FA2020 p504)
• 4 cranial nerves in the medulla (IX-XII)
• 4 in the pons (V-VIII)
• 4 above the pons (2 in the midbrain= III, IV, 2 in the cortex= I, II)
• The 4 motor nuclei that are in the midline are those that divide equally into 12 (except I and II), including III, IV, VI and XII (V, VII, IX and XII are in the lateral brainstem)

I definitely did not know this, but apparently smoking can worsen GERD due to tendency of nicotine to cause relaxation of the lower esophageal sphincter. Smoking is also linked to stomach ulcers due to interference with gastric mucosa and acid production. Just don't smoke kids. Don't do drugs. Stay in school forever like med students.

My take is that prior to confronting her or persuing a diagnosis of factitious disorder, you would want to "prove" your suspicions. The best way to do this is to measure C-peptide concentration because if she really was having odd endogenous insulin spikes, C-peptide would be elevated as well (C-peptide is released endogenously when insulin is released, thus elevated endogenous insulin secretion = elevated C-peptide). If it is factitious disorder, her C-peptide would be normal, and you could go from there.

Factitious disorder FA2020 p566

Also interesting to note that C-peptide measurement can be used in determination of the cause of hypoglycemia from medication in a diabetic - glyburide (sulfonylureas) cause increased endogenous insulin and thus C-peptide is increased in hypoglycemia caused by sulfonylurease; hypoglycemia from exogenous insulin overdose has normal C-peptide

From what I can tell, the gist of this question is that he has SCID and since the SCID child has basically no immune system (particularly because the lack of T-cell immunity) there is a higher chance of transfusion-associated graft versus host disease (TA-GVHD) so blood products have to be irradiated.

Here is a medscape reference with who requires irradiated RBCs due to increased risk of TA-GVHD for your perusing.

Incidence = number of new cases / number of people at risk in a given period of time.

This question does not give you enough data because we do not know the total number of people at risk, we do not know if some of these people had cararacts prior and thus would not be considered in the at risk population, and we do not know which are new diagnoses (let alone the amount of new diagnoses total in the year since it is supposed to be an annual incidence).

Basically, this could be used to estimate prevalence but incidence is not the same.

The study found a negative coorelation. Coorelation is used to express associations between two variables. Negative coorelation coefficients mean that there is a general inverse relationship between the variables, i.e. as one increases the other decreases.

The coorelation coefficient, r, is the slope of the relationship found between the variables.

Here is a graphical depiction of coorelation.

In hypothesis testing, the alpha value is the probability of making a Type I error. This is the type of error mentioned in the question.

• Type I error - you find a difference when a difference doens't really exist.
• One way of remembering this is that this is what scientists "want" to make: they want to find a significant difference in their data, thus it is the "first mistake" they'd make.
• Alpha is the probability you are willing to accept that you could have made a type I error (i.e. an alpha value of 0.05 means there is a 5% probability you could make a type I error and reject the null hypothesis when you should not)


• Type II error - you do not find a difference when you should have because a true difference really exists
• Beta is the probability that you make a type II error
• Power is equal to (1 - beta)
• Power can be increased by increasing sample size, and thus with a larger sample you have a lower probability of making a Type II error
• Power can also be increased by increasing expected effect size or increasing precision. It is interesting to note accuracy has no effect on power.

FA2020 p263

My way of remembering formulas for specificity and sensitivity is that sPecificity has false Positive in it and seNsitivity has false Negative. Then the other variable is the opposite.

So the formula for sPecificity = true negative / (false Positive + true negative)

• In this case, the true negative (tested negative and are actually normal) = 113
• False positive (tested positive but are actually normal) = 1

Specificity = (113) / (113+1) = 113/114 = 0.99123 = 99.123%

NOTE: Negative and positive predictive value have the name of the variables used in them!

• Negative predictive value = true negative / (true negative + false negative)
• Positive predictive value = true positive / (true positive + false positive)

FA2020 p257

Tetracyclines are bacteriostatic and bind the 30S subunit to prevent attachment of aminoacyl-tRNA. Doxycycline and other tetracyclines are commonly used for refractory acne.

Other answers:

• Ciprofloxacin is a fluoroquinilone that inhibits DNA gyrase/topoisomerase II
• Erythromycin is a macrolide that inhibits protein synthesis by blocking translocation (macroslide) binding the 23S of the 50S ribosome subunit
• Penicillin is a beta lactam that is a D-Ala-D-Ala analog that binds to penicillin binding proteins (transpeptidases) and blocks peptidoglycan cross-linking
• Rifampin is an antimycobacterial drug which inhibits DNA dependent RNA polymerase

Supraphysiologic levels of iodine can temporarily turn off thyroid peroxidase. This is the Woldd-Chaikoff effect (FA2020 p331). Thus, high levels of potassium iodide given externally will prevent organification of the radioactive iodine and allow time for clearance from the body.

Bethanechol is a muscarinic cholinergic antagonist with no action on nicotinic ACh receptors. Bethanechol is commonly used to treat urinary retention by activating bladder smooth muscle via M3 Gq receptors that function by increasing phospholipase C conversion of PIP2 (phosphoinositide) to IP3 and DAG (FA2020 p240, p237, p238).

Wrong answers:

• Atropine is a muscarinic antagonist which would non increase phosphoinositide turnover but decrease it (FA2020 p241)
• Neostigmine is an indirect cholinergic agonist that works by inhibiting acetylcholinesterase that does work at the muscarinic synapse as well and is used for myasthenia gravis as well as postoperative ileus and urinary retention
• Succinylcholine is a depolarizing muscarinic agonistnthat causes sustained depolarization and prevents contraction, used as a paralytic in anesthesia (FA2020 p551)
• Trimethaphan is a drug that counteracts cholinergic transmission at the nicotinic receptors of the autonomic ganglia and therefore blocks both the sympathetic nervous system and the parasympathetic nervous system. It is used to treat hypertension

The burnt almond smell and noncyanotic dyspnea is characteristic of cyanid poisoning. Cyanide poisoning is treated with nitrites because nitrites oxidize hemoglobin to form methamoglobin which binds cyanide, allowing less toxicity. Thiosulfate is often added to increase renal excretion as thiocyanate. Cyanide toxicity may also be treated with hydroxycobalmin, which binds cyanide.

FA2020 p667 has differentiation of cyanide from CO poisoning.

She has malignant hyperthermia which is a life-threatening complication more common with inhaled anesthetics or succinylcholine (FA2020 p550). Susceptibility is caused by mutations in RYR1 gene encoding for the voltage sensitive calcium channel. The treatment is dantrolene which blocks the release of calcium from the sarcoplasmic reticulum by blocking the ryanodine receptors (RYR).

She has > or equal to 2 symptoms including positive (hallucinations) and negative (flat affect, social withdrawal) symptoms which have been present for >6months, supporting the diagnosis of schizophrenia. Thus, she should be started on an atypical antipsychotic (i.e. olanzapine) which is first-line for schizophrenia.

Beta-thalassemia minor is the only potentially asymptomatic disease of the answer choices. It is asymptomatic because even though it leads to underproduction of the beta chain, there is compensation by increased HbA2. It causes a microcytic anemia, as seen (FA2020 p418).

• Aplastic anemia would have decrease in every cell type and would more likely be symptomatic
• Folic acid deficiency and B12 deficiency both cause macrocytic anemia, and B12 would have added neuroligic deficits
• Sickle cell disease would definitely be symptomatic and she would have history of the disease. It also causes a hemolytic anemia. Sickle cell trait could be asymptomatic.

This is a partial mole because of the presence of fetal parts. Complete moles have no fetal parts, partial moles have fetal parts(PARTial = fetal PARTs). (FA2020 p642)

This woman's cardiac arrest caused a period of loss of blood flow and ischemia in the kidney that has led to acute tubular necrosis. In ATN there is an inciting event then an oliguric phase. In ATN, there is death of renal tubular epithelial cells that slough off and form muddy brown granular casts. Keep in mind the proximal tubule and thick ascending limb are the part of the kidney most susceptible to hypoxic injury. [FA2020 p602]

This girl has an ectopic thyroid that has remained attached to the tongue by thyroglossal duct. The mass can be identified as an ectopic thyroid rather than a thyroglossal duct cyst due to the uptake to Tc99 pertectnetate. Thus, a biopsy would show thyroid follicles. (FA2020 p326)

Prader-Willi syndrome is characterized by hyperphagia, severe obesity, and intellectual disability. None of the pother disorders listed are characterized by hyperphagia to the point of Prader-willi. [FA2020 p58]

• Angelman is the other disorder of imprinting (like Prader-Willi) except it is characterized by seizures, ataxia, severe intellectual disability, and inappropriate laughter.
• Down syndrome is characterized by intellectual disability, single palmar crease, duodenal atresia and heart defects are common [FA2020 p63]
• Fragile X syndrome is the most common inherited cause of intellectual disability and is characterized by autism, long face with large jaw and everted ears, mitral valve prolapse, and hypermobile joints [FA2020 p62]
• Williams syndome is a neurodevelopmental disorder of mild intellectual disability, outgoing personality, hypercalcemia, and elvin face (Will Ferrel in Elf, FA2020 p64)

He has alpha-1 antitrypsin deficiency which is causing panacinar emphysema and liver damage. This is the major disease to think of when you have a young-ish patient who presents with liver and lung issues. (FA2020 p392)

From the stem: hyperinflation combined with decreased diffusion capacity and decreased FEV1 points toward emphysematous change; lower lobe predominance is seen in panacinar emphysema; hepatomegaly pointing to liver involvement

NOTE: diffuse idiopathic interstitial fibrosis would cause a decreased diffusion capacity, but this is a restrictive lung disease which would not have hyperinflation but instead decreased lung volume

The association of heroin overdose and "pinpoint pupils" is the big giveaway. Not sure how relevant these extreme short stem buzzword questions are anymore because I think they are moving away from them.

My take on this question is that he is about to be diagnosed with advanced stage pancreatic cancer, which has a high mortality rate. On its own, pancreatic adenocarcinoma is not associated with any of the psychological disorders. However, a diagnosis of a terminal condition or advanced cancer of any kind that would require aggressive treatment with poor prognosis would be associated with major depression. Thus, he is at most risk of major depressive disorder.

This man likely has diabetic neuropathy and thus would have neuropathic pain. Neuropathic pain is described as a burning pain as compared to the other kinds of pain.

Here are some differences between nocioceptive and neuropathic pain.

Here is a chart of descriptors used for neuropathic v nocioceptive pain.

Immunohistochemistry uses fluorescently tagged antibodies to bind specific antigens on tissues. In this case, an antibody could be directed against CD44v10 variant protein used to tag the cells in the samples that express the variant. This is also useful because it can be done on slides of paraffin embedded tissue.

• Affinity column chromatography is used to separate a biochemical mixture based on interaction between antigen/antibody, enzyme/substrate, receptor/ligand, etc. but would not be useful in pre-embedded tissues or this case
• Density gradient centrifugation is used on mixtures to separate them into components and is particularly useful in separating cell suspensions, such as in separating blood into layers to get the buffy coat with WBCs
• Northern blot is for RNA and fluorescently tags a piece of RNA present in a sample
• PCR is for identifying/anplifying a DNA segment
• Reverse transcriptase (RT) PCR is typically used to measure expression levels of an mRNA
• Southern blot is for identifying a DNA segment in a digest

Tuberous sclerosis is characterized by HAMARTOMASS [Hamartomas in CNS and skin, Angiofibromas , Mitral regurgitation, Ash-leaf spots , cardiac Rhabdomyoma, (Tuberous sclerosis), autosomal dOminant; Mental retardation (intellectual disability), renal Angiomyolipoma , Seizures, Shagreen patches, FA2020 p525]

If you didn't know what hamartomas look like (i.e. me), here is a picture of what they were describing. They also describe seizures, subependymal calcified nodules (likely hamartomas of the CNS), and a cardiac mass, which is likely a rhabdomyoma. These are characteristic of Tuberous Sclerosis.

Wrong answer explanations:

• Familial hypertrophic cardiomyopathy is associated with sudden death in athletes, not seizures and hamartomas.
• Gardner Syndrome is also called familial colorectal polyposis and is a form of familial adenomatous polyposis.
• Glycogen storage disease Type I is Von Gierke disease, which presents with hepatosplenomegaly and severe fasting hypoglycemia typically in infancy.
• Multiple Endocrine Neoplasia Type I is associated with all the P's -> Pancreatic, Parathyroid, and Pituitary (pancreatic endocrine tumors, parathyroid adenomas, and pituitary tumors)

The stem describes tenderness in the anatomical snuffbox ("radial aspect of the wrist between the abductor pollicis longus and extensor pollicic brevis"). This is indivative of a fracture of the scaphoid bone. One of the more common complications is avascular necrosis of the proximal scaphoid bone. [FA2020 p449]

Osteomalacia is defective mineralization of osteoid and can be caused by vitamin D deficiency. Because of the deficiency in vitamin D, there is decreased absorption of calcium in the gut leading to overall hypocalcemia. This hypocalcemia causes increased excretion of PTH, but since PTH uses vitamin D to mediate its effects the calcium deficit is not corrected. This results in overall decrease of Ca2+ with increase of PTH.

FA2020 p463 and p70

She has left homomynous hemianopia, which can be due to lesion of the contralateral optic tract or as in this case lesion to the contralateral occipital lobe. It is not mentioned explicitly but this causes macular sparing. (FA2020 p542 gives the visual field defects)

A furuncle is a boil, typically caused by staphylococcal infection. Thus, it can be deduced that the food poisoning is due to staphylococcus aureus, which forms a heat stabile enterotoxin not destroyed by cooking. Ingestion of the preformed enterotoxin causes vomiting.

Based on the systemic findings (weight loss, night sweats, cachectic, looks chronically ill) and emigration from India (where TB is more common so the NBME likes to throw it in), miliary TB should be suspected. (FA2020 p140).

None of the other answers would cause the generalized illness to the same degree as TB.

Pulsatile mass in the abdomen combined with severe abdominal pain, decreased blood pressure, pail and lethargic all point to dissection of an abdominal aortic aneurysm. This would cause decreased femoral pulses due to loss of blood flow to the lower extremities.

Key aspects to knowing this is dilated caridomyopathy:

• S3 - S3 is a heart sound associated with dilated cardiomyopathy and heart failure (increased filling pressures, may also be associated with mitral and aortic regurg but those would be associated with a murmur, FA2020 p287)
• Displaced apical impulse and cardiomegaly - dilated cardiomypathy makes a big heart (FA2020 p308)
• Reduced ejection fractions, swelling, shortness of breath - signs of decompensated heart failure, reduced ejection fraction is a sign of systolic dysfunction (not diastolic dysfunction as seen with resrtictive diseases, p309)

Based on the question stem and the autoanitbodies given (butterfly rash combined with anti-dsDNA/anti-Sm/antiphospholipid), this woman has classic lupus. SLE is associated with cytopenias, so thrombocytopenia is the best choice of the available answers. Thrombocytopenia is common in lupus (FA2020 p470)

• HUS is associated with E.coli or Shigella infection and not Lupus. Lupus kidney disease is diffuse proliferative glomerulonephritis.
• Macrocytic anemia is typically caused by B12 or folate deficiency and not associated with lupus. Lupus anemia is typically anemia of chronic disease, which is normocytic, or due to inadequate RBC production or iron deficiency, which is microcytic.
• Multiple nucleated erythrocytes are found in leukemias when the RBCs are being "pushed" out of the bone marrow, or in diseases where the bone marrow is highly stressed. Lupus does not typically cause this.
• I am not 100% sure why rouleax formation is wrong, because as far as I understand any condition that increases monoclonal Abs can cause rouleaux formation, but I am assuming it is just not as common/likely, hence thrombocytopenia which is very common is the better answer

I don't like this question for many reasons, but basically he has sarcoidosis (noncaseating granulomas with no pathogen found on biopsy) which according to First Aid is more common in African-American females. Since he is African-American that is his risk factor (FA2020 p676).

Lentigo maligna is a type of melanoma (FA2020 p484), hence why it is important the lesion is brown/black with irregular borders and enlarging (all hallmarks of melanoma). The biopsy description also fits lentigo maligna, but even if you are not a pathologist the description that fits cancer and and "atypical melanocytes" should point you to lentigo maligna.

• Acanthosis nigricans is thickening (acanthosis means epidermal hyperplasia) and darkening of skin in folds and creases associated with insulin resistance
• Actinic keratosis is a premalignant lesion that is a small, rough, erethematous or brownish papule/plaque
• Compound nevus is a type of mole that is slightly elevated, brown or light brown, and has regular borders. It is not fast-growing.
• Sebhorreic keratosis are "stuck-on" flat, greasy, pigmented squamous epithelial proliferation of immature keratinocytes with keratin-filled cysts. Rapid onset of multiple indicates possible GI malignancy.

FA2020 p482, 477 and 484

Multiple Myeloma CRAB: (FA2020 p431)

• hyperCalcemia
• Renal involement
• Anemia
• Bone lytic lesions and Back pain

Multiple myeloma is also associated with rouleaux formation because of increased serum protein (in this case globulin chains from secreting plasma cells). Rouleaux formation increases sedimentation rate.

Salmonella is a common cause of osteomyelitis in sickle cell patients (FA2020 p422). Apparently this is a fact they want us to know.

Giant cell (temporal) arteritis commonly presents in older females with unilateral headache and sudden loss of vision. Swelling and tenderness over the temporal artery is also a common finding. Elevated ESR also points to the diagnosis. (FA2020 p314).

ALS would present more commonly with upper and lower motor neuron signs together. Cerebral infarction presents with different stroke signs, and this presentation does not fit any potential stroke presentation (found FA2020 p514). Though multiple sclerosis may present with acute optic neuritis (painful vision loss), it is a relapsing/remitting course of disease and more commonly presents in women in their 20-30s; it also would not be associated with elevated ESR or swelling. Trigeminal neuralgia is episodes of shooting/shocking pain in a trigeminal region that typically lasts less than 15 minutes, not for days as described here.

Normal pressure hydrocephalus presents with the classic triad of "wet, wobbly, and wacky":

• Wet - urinary incontinence
• Wobbly - gait apraxia
• Wacky - cognitive dysfunction (memory issues)

FA2020 p522

According to the BrosWorld deck, they tend to try to hide the classic triad in longer stems (such as this one), even though they give the triad outright in the first sentence.

Pick disease is the old name for frontotemporal dementia and early changes are more likely to be personality change or aphasia. Alzheimers is a slow progression of memory loss and not typically associated with urinary incontinence. Parkinson would typically present with symptoms like tremor, rigidity, or shuffling gait. A cerebral neoplasm can cause a variety of neurologic symptoms but is more likely to present with symptoms like headaches and focal neurologic deficits.

Segmented neutrophils should be the largest population of leukocytes. This girl has had a very low neutrophil population since birth, indicative of congenital neutropenia. All other cell counts are normal (RBC count and hematocrit at birth are actually high but normalize by 1 month).

None of the other disorders would cause severe neutropenia. SCID and DiGeorge are more likely to have lymphopenia. Congenital CMV causes hearing loss, seizures, rash, chorioretinitis, and periventricular calcifications. Alloimmune hemolytic disease of the newborn would present with anemia.

The most common hormone secreting tumor of the pituitary is a prolactinoma (FA2020 p526)

The inferior constrictor is innervated by the vagus nerve (all pharyngeal muscles except the stylopharyngeus are innervated by the vagus nerve; the stylopharyngeus is innervated by the glossopharyngeal). It is motor fibers because these muscles are involuntary skeletal muscles.

This individual has Zenker Diverticulum, which leads to an outpouching between the thyropharyngeus and cricopharyngeus and presents with the symptoms described (dysphagia, halitosis, FA2020 p384).

Here is a 2.5 minute video on the pharyngeal constrictors and innervation if you are a more visual learner.

Here is an image of the pharynx and innervation.

This woman has pulmonary hypertension, likely pulmonary arterial hypertension characterized by increased pulmonary artery pressure with a normal pulmonary capillary wedge pressure (remember pulmonary capillary wedge pressure is associated with left atrial pressure). PAH endothelial dysfunction causes an imbalance in vasoconstrictors (such as endothelin) and vasodilators (NO and prostacyclin). [FA2020 p679]

BosENtan, used to treat PAH, is an ENdothelin antagonist (FA2020 p686)

This is staphylococcal toxis shock syndrome, commonly associated with tampon use or nasal packing (as in this case). TSST1 (toxic shock syndrome toxin) is a superantigen that nonspecifically activates T-lymphocytes by binding to MHC II and the TCR. (FA2020 p135)

He has cystic fibrosis which is an autosomal recessive disease. You can tell its CF because these individuals are more likely to have pseudomonas colonization and they have high sweat chloride due to a defect in the CFTR ATP-gated chloride channel. (FA2020 p60)

Clostridium perfringins is a common cause of myonecrosis and would be described as a large gram(+) rod (FA2020p138).

• Bacillis subtilis is a motile gram + rod known as hay bacillis found in soil and the intestines of humans. It is almost never pathogenic and used in probiotic supplements.
• Bacteroides fragilis is an anaerobe like clostridia but it is a gram negative rod. It is found in lung abscesses from aspiration.
• Listeria monocytogenes is a gram positive rod but it is more associated with consumption of unpasturized dairy or deli meats and it causes listeriosis which can present from mild gastroenteritis to meningitis. It can be associated with sepsis but more commonly in the elderly, immunocompromised, or newborns and would not be associated with myonecrosis.
• StaphyloCOCCUS aureus is a gram positive cocci.

This man has acute intermittent porphyria which is a deficiency in porphobilinogen deaminase because: (FA2020 p425)

• Painful abdomen
• Port-wine colored urine (burgundy urine)
• Precipitated by drugs - triggered by TMP/SMX
• Psychological disturbances - irrational behavior
• Family history
• Increased 5-ALA and porphobilinogen which are the two prior substances in the heme synthesis pathway that would be backed up

For gonadal drainage: (FA2020 p624)

• Testes/ovaries drain to paraaortic lymph nodes
• Body of uterus/cervix/superior bladder to external iliac
• Prostate/corpus cavernosum, proximal vagina/cervix, and anus above pectinate to internal iliac
• Distal vagina/vulva, scrotum, and anus below pectinate to superficial inguinal
• Glans penis to deep inguinal

Basically, the superficial inguinal drains the skin below the umbilicus (except the popliteal area) and the other answers except the correct one are not associated with gonadal drainage

Lymph drainage FA2020 p97

Pregnancy causes hypervolemia which can increase the risk of aortic dissection in Marfans syndrome

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721114/)

The -navirs are protease inhibitors, so a mutation in protein processing would cause resistance.

She has rheumatoid arthritis which characteristically has rheumatoid factor and anti-cyclic citrullinated peptide (more specific). Rheumatoid factor is IgM reactive with the IgG Fc region (FA2020 p115)

Statins (which are HMG-CoA reductase inhibitors and inhibitors of cholesterol synthesis) cause upregulation of the LDL receptor and increase in LDL receptor recycling.

This woman is taking lithium which predisposes her to nephrogenic diabetes insipidus, where the kidney stops responding appropriately to antidiuretic hormone (ADH). This leads to urine dilution and plasma concentration, causing hypernatremia and excessive thirst/urination.

ADH has its primary site of action in the collectung ducts of the kidney, so the abnormal function is in the collecting ducts.

FA2020 p574, 338, and 392

Here, we want to know loading dose which is equal to the volume of distribution x target concentration in plasma.

So our loading dose = 1.81L/kg x 10mg = 18.1mg/kg

She is a 55kg person so 18.1mg/kg x 55kg = 995.5 mg which approximates to 1000mg total loading dose.

Important Pharm Equations to Remember

This patient likely has Gilbert syndrome (FA2020 p394).

This is because his hyperbilirubinemia occurs during periods of stress and is relatively benign. Gilbert's syndrome has elevated unconjugated bilirubin because there is a mild deficiency in UDP-glucuronyltransferase conjugation. Thus, the cause is decreased conjugation of bilirubin.

Carotid sinus massage is a mechanism of inducing activation of the parasympathetic system. This is because the baroreceptors in the carotid sinus.

Caortid sinus massage --> activation and increased firing of baroreceptors --> transmission to solitary nucleus via glossopharyngeal nerve --> decreased sympathetic output and increased parasymapthetic output v --> increased AV node refractory period and decreased HR

FA2020 p296

The ductus arteriosus is kept patent by prostaglandins (which is why the baby is started on a prostaglandin drip id we need to keep the ductus patent in some hypoxic congenital heart diseases).

Thus, to close the PDA, prostaglandins are decreased. cyclooxygenase inhibition (COX) is one way of decreasing prostaglandins and is the physiologic way of closing the ductus as well as how we close it if necessary (to close a PDA you give a baby NSAIDs, FA2020 p486).

Ejection fraction = (EDV-ESV) / EDV

Basically it is the amount of blood they get out in a stroke, so it would be the blood in before minus the blood left after a stroke/systole, divided by the blood in before the stroke.

FA2020 p285

A cleft lip/palate with no associated anomalies has multifactorial etiology (FA2020 p621). There is no evidence of associated syndrome or inheritance, so it is multifactorial.

Here is a simplified image of the NF-kappaB pathway. NF-kB is important in transcription of inflammatory genes. A lot of PAMPs (pathogen associated molecular patterns) and inflammatory signals lead to activation of NF-kB which in turn mediates a whole heck of a lot of immune-related responses.

Botulism toxin acts via proteases that cleave SNARE and prevent acetylcholine release at the neuromuscular junction (FA2020 p132). Thus, it does not directly affect the post-synatpric muscle cell. If you add external acetylcholine, you would still have a completely normal response. This eliminates all but two answers.

The end plate potential (EPP) would be affected by botulism toxin because the end plate potential is the change in voltage that occurs at the postsynaptic muscle motor endplate after an action potential in the motor neuron axon triggers release of many acetylcholine vesicles. Normally, an action potential in the motor neuron will cause influx of calcium that leads to fusion of Ach vesicles (requiring SNARE) and exocytosis, releasing large quantities of Ach into the synapse which can then bind and trigger an EPP in the muscle. With botulism, fusion of the Ach vesicles is inhibited so less Ach is released and the EPP is blunted. Notably, the voltage is the same as the mEPP which is the voltage after random occurrence of Ach release (see below).

A miniature end plate potential (mEPP) is the voltage change that occurs when one vesicle of acetylcholine is released. These occur randomly. mEPP would not be affected by botulism toxin because it is the produce of random fusion of a vesicle which could still occur after administration of botulism toxin.

Here is an image reminding the difference between EPP and mEPP.

Based on the history (consumption of large amounts of alcohol and elevated serum amylase/lipase with hypocalcemia), this man likely has acute pancreatitis (FA2020 p397). One of the major complications is autodigestion of tissues, such as what is seen in the image.

Barbituate overdose causes CNS depression that can lead to hypoventilation. In Hypoventilation due to CNS depression, there is hypoxemia with a normal A-a gradient because the alveoli themselves are not injured and rather there is simply less oxygen overall reaching the alveoli due (FA2020 p669). A normal A-a gradient is around 10 mmHg (estimated as age/4+4, FA2020 p668). CO2 will also be increased because of retention of more "stale air" in the alveoli and lower respiration which allows less expiration of CO2.

Deoxyhemoglobin has a higher pKa than oxyhemaglobin and thus will accept hydrogen ions more readily. This is important in the ability to "carry" CO2 as the main mechanism of CO2 transport is actually conversion of CO2 to HCO3- (CO2 + H2O -> HCO3- + H+), thus deoxyhemaglobin carries the H+ while HCO3- is transported in the plasma to the lungs. Carbaminohemaglobin is actually only about 20% of the CO2 trasnport and CO2 dissolved as CO2 is 10%; trasnport as HCO3- is around 70% of the CO2 transport.

Here is another image of the process.

Another important aspect of the process to take note of that they like to ask about is the chloride shift. Chloride moves the opposite direction as HCO3- in the RBC. Thus at tissues where we are generating HCO3- from CO2 and need to pump it out of the cell, chloride moves into the cell.At the alveoli where we need to pump HCO3- back into the RBC to turn it into CO2, chloride moves out of the cell.

Other answers:

• 2,3BPG will bind and stabilizes deoxyhemaglobin making it less attracted to oxygen, shifting the hemaglobin dissosiation curve right.
• Deoxyhemaglobin has a higher capacity to form carbanimohemaglobin
• Deoxyhemaglobin has a higher pKA than oxyhemaglobin (this is why it can accept hydrogen ions more readily)
• Competition for binding site is not a major mechanism for the ability to carry CO2 as most CO2 is "carried" by conversion to HCO3-
• Nitric oxide binding is not a mechanism of CO2 carry.

Important aspects of volatile (gas) anesthetics: (FA2020 p549):

• MAC (minimum alveolar concentration): essentially the ED50 for inhaled anesthetics, this is the minimum concentration of anesthetic that causes a response in 50% of patients
• LOW MAC means HIGH potency - more potent drugs would have a lower minimum amount needed to be present in the alveoli in order to exert their effect.
• LOW MAC is related to HIGH lipid solubility (higher oil/gas partition coefficient) - more lipid soluble agents tend to be more potent because of their increased ability to cross the BBB
• MACs are additive (i.e. one gas at 1.5 MAC = two gases at 0.75 their respective MACs)
• Blood/gas partition coefficient: an expression of solubility; anesthetics with a low blood gas partition coefficient have a rapid onset/offset
• i.e. LESS plasma solubule anesthetic = FASTER onset/offset
• This is because less plasma soluble agents will "fill up" their maximum amount in the blood reservoir quicker and thus are pushed down their concentration gradient into the brain quicker; i.e. they quickly saturate the blood and will move on to affecting the brain quicker
• MAC and blood/gas partition coefficient also tend to be inversely related -- higher MAC = lower blood/gas partition coefficient and vice versa; thus many of the more potent anesthetics have a longer time for onset/offset

This woman has a carcinoid tumor, associated with carcinoid syndrome characterized by flushing, wheezing, and diarrhea. (FA2020 p 352) Based on her CXR I'd say she probably has a bronchial carcinoid tumor. Tumor cells would be chromogranin(+).

Carcinoid syndrome is a paraneoplastic syndrome caused by secretion of serotonin (5-HT). It is treated with a somatostatin analog like octreotide and the presence of 5-HIAA in the urine can be a marker (5-HIAA is a serotonin breakdown product).

EBV is associated with nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and primary CNS B-cell lymphoma. (FA2020 p226 for oncogenic microbes)

This indicidual has CATCH22 DiGeorge Syndrome, caused by failure in the development of the 3rd and 4th pharyngeal pouches (FA2020 p116). This is evidenced by the hypocalcemia (agenesis of parathyroids), facial deformities, and conotruncal abnormality (right sided aortic arch).

Big thing is being able to ensure you know it is pharyngeal POUCH not cleft or arch. Pharyngeal arch derivatives are on FA2020 p620. Pharyngeal pouch derivatives are p621. And pharyngeal cleft derivatives are p619. (Aortic arch derivatives are p619 as well, if you want to complete the circle)

Treacher-Collins is error in 1st and 2nd pharyngeal arch derivatives which can present with craniofacial abnormalities, zygomatic and mandibular hypoplasia, and hearing loss. Pierre Robin is similar and presents with micrognathia, glossoptosis, cleft palate, and airway obstruction. Neither of these would present with hypocalcemia.

Here is a summary of derivatives of neural crest cells. Also FA2020 p613 for embryologic derivatives [MOTEL PASSES - Melanocytes, Odontoblasts, Tracheal cartilage, Enterochromaffin cells, Leptomeninges (arachnoid, pia), PNS ganglia (cranial, dorsal root, autonomic), Adrenal medulla, Schwann cells, Spiral membrane (aorticopulmonary septum), Endocardial cushions (also derived partially from mesoderm), Skull bones]

Premature infants have a lack of surfactant which decreases compliance of the lungs and increases the lung elastic recoil (FA2020 p665).

The high surface tension is the main contributor to elastic recoil in the lung of a neonate. Because the surface tension is high due to lack of surfactant, recoil is also high, and the lungs and alveoli have more tendancy to collapse.

Unpasturized dairy is a huge clue for Listeria. Listeria is also a gram(+) coccobacilli [FA2020 p139]

This is a case of albinism, most likely due to decreased tyrosinase activity or decreased tyrosine transport (both are required in synthesis of melanin). Thus, there is a normal number of melanocytes and a decreased amount of melanin.

Vitilligo (characterized by irregular hypopigmented patches) is caused by destruction of melanocytes and thus would have decreased melanocytes.

FA2020 p476

Here is my take: a ventricular septal defect in infancy allows for left to right shunting of blood in the ventricles. This causes an increased pressure in the right ventricle (due to more blood being pushed into it) and a decreased pressure in the left ventricle. Because there is more blood in the pulmonary circulation from the shunt, I think the left atrial pressure would also be increased in an early VSD.

SO when you repair the VSD, the left ventricle pressure will be increased compared to when the shunt was present (it is no longer losing blood), the right ventricle pressure will be decreased (it is no longer getting blood from the shunt), and the left atrial pressure will be decreased (there is no longer overload of the pulmonary system returning to the left atrium).

FA2020 p298

Parathyroid hormone is responsible for increasing blood calcium by ultimately increasing gut absorption, increasing bone resorption, and increasing kidney reabsorption. Since it serves to increase gut absorption of calcium, concentration in the feces would be decreased. (FA2020 p332)

This woman has the classic signs of vitamin C deficiency, or scurvy: easy bruising, petichiae, perifollicular hemorrhages, gum disease, and slow wound healing. Vitamin C is necessary for proper hydroxylation of proline and lysine in collagen. (FA2020 p69 [nice])

Thyroid hormone has an intracellular receptor which binds to DNA, thus the only answer that makes sense is nuclear/retinoid X binding to DNA (FA2020 p337). Other things that have intracellular receptors are steroid hormones and vitamin D.

Chloroquine does not adequately kill the dormant liver form of malaria (hypnozoite), and thus for infections that have a hypnozoite stage treatment requires addition of primaquine (which does adequately kill hypnozoites) to prevent relapse from release of the infection back into the blood. [FA2020 p157]

Hypnozoites are the dormant form of malaria in the liver (think hypno as in sleeping from hypnosis). Plasmodium vivax and ovale have the hypnozoite stage and thus require the addition of primaquine.

Though ampicillin and ceftriaxone are both considered beta lactam antibiotics, Most cephalosporins have intrinsic resistance to the beta-lactamases that inactivate other beta-lactams (FA2020 p189). Cephalospoin resistance is caused by structural changes in the transpeptidases (also called penicillin binding protein), or inactivation by cephalosporinases (a specific type of beta-lactamase)

The kidney converts 25-hydroxycholecalciferol into 1,25-hydroxycholecalciferol (FA2020 p70).

Here is an image with the steps of active vitamin D synthesis.

One of the more important things to know about tamoxifen is that it is an estrogen antagonist in the breast but agonist in the uterus and bone. (FA2020 p443 and p656). This causes increased risk of endometrial hyperplasia and cancer on tamoxifen.

NOTE: Even though it is agonist in bone (technically), it is not used commonly for postmenopausal therapy for osteoporosis due to the agonist activity in the uterus. Raloxifene is used instead, which is agonist at bone but antagonist at breast and uterus. Raloxifene is not as strong as an antagonist at breast so it is not used for breast cancer treatment.

This man has overdosed (potentially on opioids due to the severe respiratory depression), which is causing him to hypoventilate (less breaths/minute and shallow breaths).

Hypoventilation leads to:

• Decreased O2 from decreased overall ventilation
• Increased CO2 because you are not expelling as much CO2 in breaths. He is also retaining more residual air with shallow breaths so there is more CO2.
• Acidosis from retained CO2
• Slightly increased bicarb (from normal of 24mEq/L) but not fully compensated because this is primarily a respiratory alkalosis and compensation thus takes time

Lipopolysaccharide, or LPS, is the primary endotoxin mediator of gram(-) sepsis leading to septic shock. This woman likely has sepsis from E. coli, a gram negative bacterium which produces LPS, based on her history indicating a UTI. E.coli are the most common cause of UTI. (FA2020 p133)

This is left homonomous hemianopia, which is caused by lesion to the contralateral optic tract (D). This occurs because the nasal retinal fibers (temporal visual field) cross at the optic chiasm while the temporal retinal fibers (nasal visual field) do not. See FA2020 p542 or here for image.

Lesion of the optic nerve (A or C) would cause complete blindness in either eye.

Lesion of the optic chiasm (B) causes bitemporal hemianopia.

Lesion to the left optic tract (E) would cause right homonomous hemianopia.

F and G are the oculomotor nerves.

The description points to pancreatic insufficiency due to steatorrhea (fat in the stool, likely due to insufficiency of pancreatic lipase) and muscle fiber in the stool (which points to incomplete protein digestion, likely due to insufficiency of pancreatic proteases).

Further, he has no deficiency in carbohydrate absorption as evidenced by the D-xylose test (which indicates an intact mucosa for absorption and does not require digestive enzymes, FA2020 p373); and he has no abnormalities on biopsy of the intestine.

Thus, the primary issue is pancreatic insufficiency and supplementation of pancreatic enzymes is most helpful.

The median nerve is responsible for abduction of the thumb and sensation over the first three digits.

It is also the nerve commonly compressed in carpal tunnel syndrome which gives similar symptoms (FA2020 p459, 451)

The combination of recurrent sinopulmonary/ear infections and situs invertus (right sided heart tones and right sided stomach bubble) indicate Kartagener's Syndrome, a defect in dynein. Sinopulmonary infections are predisposed due to the lack of active cilia, and situs invertus is common due to the necessity of cilia in establishing the body axis.

FA2020 p49

Clostridium tetani and Cornybacterium diphtheriae are part of an inactivated toxoid vaccine with Bordatella pertussis (Tdap and DTap consist of Tetanus toxoid, diptheria toxoid, and acellular pertussis, hence ap)

FA2020 p111

This woman has a mature cystic teratoma, which in females is usually benign. This can be deduced from the presence of multiple mature tissues from all three germ layers that are not normally native to the ovary. Teratomas are derived from germ cells. (FA2020 p646)

Note to keep in mind: immature teratomas and other germ cell tumors are malignant in females, and in males even mature teratomas of the testes also may be malignant (all germ cell tumors in males are malignant)

C3,4,5 keep the diaphragm alive (i.e. the phrenic nerve) and irritation of the diaphragm can cause referred pain to the left shoulder due to C5 (FA2020 p663).

Lesion of the hippocampus results in anterograde amnesia (FA2020 p511, think 50 First Dates kind of forgetting).

Also, the hippocampus is one of the most vulnerable places to ischemic injury (pyramidal cells of the hippocampus, p512)

FA2020 p144

An USMLE testable fact about salmonella species is that antibiotic use actually prolongs the excretion of the organism. Fun fact(?) for memorization as there is no clear answer as to why that I could find.

Key aspects of the question:

• Hypokinesis of the posterior left ventricle with increasing activity levels - in my opinion this is the primary clue to stenosis of the right coronary artery. This is because the posterior heart is supplied by the posterior descending artery, which in most people who have right dominant coronary circulation is a branch of the right coronary artery.
• "When climbing stairs" and the hypokinesis being present on stress testing - this helps you to know the condition is only exacerbated in exercise, and stenosis of the RCA generates symptoms in exercise because in excersise the increase in oxygen demand typically causes dilation of the coronary vessels to accomadate. When there is stenosis, the vessel cannot dilate and thus there is transient ischemia of the area the vessel supplies (this is potentially exacerbated by the coronary steal phenomenon in a stress test which can occur with administration of vasodilators) FA2020 p304

Increase in oxygen consumption is the normal response to exercise and alone is not pathologic. Extravascular compression of the coronary arteries is also considered normal and nonpathologic; this is why most coronary blood flow occurs during diastole and why the endocardium is most susceptible to ischemia.

The primary mechanism of inflammation "tumor" or swelling is increased permeability of the endothelium which leads to leakage of fluids (FA2020 p213)

Here is a normal hysterosalpingogram.

Comparing this to the image given, you can see there is no entrance of the dye into either fallopian tube or spillage, so both are blocked.

This woman has Polycystic ovarian syndrome. This can be deduced because of the high LH:FSH ratio (>2), high BMI, and presence of withdrawal bleeding in a progesterone withdrawal test. In polycystic ovarian syndrome, there is increased release of androgens from theca interna cells. These androgens can cause symtoms commonly associated with PCOS (hirsutism, acne) but can also be aromatized to estrogen in adipose tissue. The presence of estrogens in this form causes constant negative feedback on the hypothalamus and dysregulation in the appropriate levels of the gonadotropins (see here and here)

Here is a comparison graph of the hormone levels in a normal menstrual cycle to PCOS.

A progesterone withdrawal test is used to help determine the cause of amenhorria. If withdaral bleeding occurs, it means the patient has sufficient estradiol and the amenorrhia is due to anovulation. If no withdrawal bleeding occurs, it means the patient either has chronic anovulation without estrogen, a nonreactive endometrium, or a problem with uterine outflow. In our patient's case, she has withdrawal bleeding so she has anovulation, a common symptom of polycystic ovarian syndrome.

FA2020 p 612 has early fetal development. Here are the explanations for the answers:

• The syncytiotrophoblast mediates early implantation in the first week and this is when hCG secretion begins. Further, it forms concuttently with the cytotrophoblast from the trophoblast.
• The bilaminar disc (two layers) is present during week two, and gastrulation occurs during week 3 and 3 germ layers are the product.
• The neural tube is not fully formed until day 21 but the neural plate is formed on day 18 (FA2020 p490)
• The embryo is NOT resistant to teratogens here, neural tube defects can occur if the embry is exposed to teratogens in week 3. Earlier than this the embryo is in an "all or nothing" stage and death of the embryo is more likely to occur if the embryo is exposed.
• The somites form adjacent to the neural groove prior to sclerotome migration.

Basically, even without knowing all the exact days of development, most answers can be eliminated based on having the events in the incorrect order or having an incorrect aspect about development (i.e. the syncytiotrophoblast forms concurrent with the cytotrophobast, 3 germ layers are present after gastrulation, the embryo is never truly resistant to teratogens after implantation, the sclerotome forms from somites so somites have to come first).

Here is a general overview of the first three weeks of development after fertilization.

Here is another one if that doesn't do it for ya.

The esophagus is a component of the foregut of the gut tube, which is lined with endoderm. Pure esophageal atresia can occur due to failure to recanalize. (FA2020 p359) See here for slide explanation.

Here is another diagram of the esophagus and laryngotracheal tube development showing the lumen lined with endoderm covered in splanchnic mesoderm.

There are a few ways to get to the answer of the splice error:

• The mutation caused "skipping" of an exon. Splicing is the process where introns are spliced out and exons are spliced together before exporting the mRNA. Retained introns or skipping of an exon is likely a result of an error in splicing.
• The mutation itsself is GT to AT. In RNA this would be GU to AU. GU is a known component of the 5' splice site (FA2020p42), so this also points to splice site mutation.
• None of the other mutations adequately describe why an exon would be skipped. You could reason a nonsense mutation (a mutation that introduces a stop codon) could "skip" the last exon or so because it trunctuates the protein. However, the mutation does not fit any that introduce a stop codon (the stop codons are UAA, UGA, and UAG... none of these have AU in them!)

Other info: this boy has phenylketonuria, though multiple mutations can lead to this so it would not help in answering this question.

This is likely Herpes Simplex Virus 1 (based on the vesicular lesions on the lip) which remains dormant in sensory ganglia, most commonly the trigeminal ganglion (FA2020 p164).

Peroxisomes are where degradation of very long chain fatty acids occurs (as well as phytanic which is a branched chain fatty acid and pipecolic which is an alpha amino acid) [FA2020 p47]

This is intranuclear opthalmoplegia, associated with damage to the medial longitudinal fasciculus (MLF). If you haven't really memorized this yet because you thought this was a minor thing (like me) you should because they really enjoy asking questions on it according to basically every practice test. (FA2020 p543)

How you know:

• She has a conjugate gaze palsy of adduction but she can still converge (i.e. the medial rectus is not paralyzed because she can still cross here eyes)
• It is more commonly seen in MS

TL;DR: Even with Type I or II renal tubular acidosis the ammoniagenesis from glutamine is not impaired and thus is the main source of ammonia.

Here is my take: Based on her history and measured plasma values, this girl likely has one of the "low potassium" renal tubular acidoses, either Type I or Type II (see this chart for reasoning based on measured values or this image for fun colorful renal tubular acidosis and FA2020 p593)

Then, we are told that she has a defect in "ammoniagenesis". In the renal tubules, ammonia is generated in two primary ways: via direct conversion of glutamine to ammonia in the proximal tubule which is then secreted into the tubule, or by NH3 combining with with H+ in the collecting tubules (which I guess they are considering a separate ammoniagenesis pathway even though its all kinda related?). See this diagram or this diagram

Assuming our girl has Type I renal tubular acidosis, there will be decreased availability of hydrogen ions in the renal tubules to combine with NH3. Thus, the primary source of ammonia production in this patient will be glutamine (which is the major source of ammoniagenesis in a normal person anyways).

Further reasoning - Type I is impaired secretion of hydrogen ions into the lumen, so there will be less hydrogen ions available. She likely has type I because this is primarily treated with potassium citrate (both to buffer and to prevent renal stones which are a common complication). Even if she had Type II the increased excretion of bicarb would also buffer more H+ leaving less for ammoniagenesis in the NH3/H+ combination fashion.

Contrarily, Type 4 renal tubular acidosis (hyperkalemic) results in decreased synthesis of ammonia in the proximal tubules, which we know she does not have because of her low potassium.

The proteasome degrades ubiquitin-tagged proteins into amino acids and releases ubiquitin for recycling.

See here for picture illustration of the process.

This has to do with incidence of the disease.

• Incidence = number of new cases / total number AT RISK in a certain time period

In the first year, the incidence of the disease is 32/1000 = 3.2%

32 people are removed from the population for treatment, and we are assuming other variables remain the same meaning incidence remains the same. The new number of people infected in the next year will be 3.2% x AT RISK population:

• 3.2% x (1000 - 32) = 30.976 ~ 31 people

Interviewing the subjects as a means of measuring the exposure introduces the risk of recall bias which would bias the measurement of the exposure. Recall bias occurs when individuals with a disease tend to recall exposure more in retrospective studies (FA2020 p260)

Occult blood testing of the stool has a notoriously low sensitivity for picking up cancer (i.e. it has a very high rate of false negatives), and thus in this individual with an increased risk of colorectal cancer based on family history you would not want to use occult blood test for fear of a false negative result (where the test was negative but the individual actually had cancer).

"It exhibited a sensitivity of 12.9%-79.4% with a specificity of 86.7%-97.7% for CRC screening in many studies."

FA2020 p388 lists screening guidelines for colorectal cancer.

In this individual with what would be considered a higher pretest probability, the test would be known to have a higher positive predictive value and a lower negative predictive value. It is not uncertainty surrounding these that would affect the decision (FA2020 p257)

As sample size increases, confidence interval narrows (FA2020 p263). So decreasing the sample size would increase the width of the confidence interval.

If you are like me and need a rationale for this rather than just memorization, this happens because the standard error decreases with increasing sample size.

• Remember a 95% confidence interval is approximately equal to the sample mean +/- 2(SE).
• The Standard Error is equal to the standard deviation divided by the square root of the sample size
• SO if you increase the sample size, you decrease the SE which decreases the width of the confidence interval

Here is a good general explanation of confidence intervals, confidence level, and sample size with numbers:

http://www.opentextbooks.org.hk/ditatopic/9471

The girl is having absence seizures (staring into space, 3 second bursts of 3/sec spike-and-wave activity). The first-line treatment for absence seizures is ethosuximide. (FA2020 p544 and 517)

He presents with an anticholinergic toxidrome: hot as a hare, dry as a bone, mad as a hatter (FA2020 p241, the anticholinergic toxidrome is the same as an atropine overdose and jimsonweed actually contains atropine).

The antidote for antichlinergics is phyostigmine, an acetylcholinesterase inhibitor that acts as an indirect cholinergic agonist. (FA2020 p240)

Cimetidine is one of the cytochrome p450 inhibitors which would allow increase of the concentration of diazepam to toxic levels by inhibiting its elimination. (https://en.wikipedia.org/wiki/Diazepam)

SICKFACES.COM when I Am Really drinking Grapefruit Juice (FA2020 p252)

HbS homozygosity indicates Sickle Cell disease. Streptococcus pneumoniae is associated with sepsis in patients with Sickle Cell (due to autosplenectomy causing increased risk of infections with encapsulated organisms) [FA2020 p136 and 422]

Streptococcus pneumoniae is susceptible to penicillin and prophylactic penicillin can decrease risk of infection.

Sickle cell patients would also be at increased risk of infection with E.coli, H. influenzae and neisseria (as they are encapsulated, p127) but they run less of a risk than Strep pneumo than causing sepsis in sickle cell patients. Salmonella is the most common cause of osteomyelitis in sickle cell patients but again is not what we would primarily be concerned with in this baby.

https://pediatrics.aappublications.org/content/141/3/e20172182

Praziquantel is one of the anthelminthic therapies used to treat cestodes and trematodes (FA2020 p200).

Specifically, this girl is presenting with Schistosoma mansoni, diagnosable by the appearance of the egg with a lateral spine in the stool (FA2020 p160). Schistosoma mansoni causes hepatosplenomegaly and ascites due to a propensity for infection of the liver leading to granulomatous reaction and fibrosis. Freshwater snails are the intermediate host with transmission occurring in freshwater, and specifically S. mansoni is found widely across Subsaharan Africa and parts of South America.

Here is a good atricle for additional info on Schistosoma and its species.

The other important schistosoma to know is S. haematobium which infects the bladder and is associated with squamous cell carcinoma of the bladder.

Ondansetron is a powerful antiemetic that works by antagonizing serotonin 5HT3 receptors. It is given for postoperative nausea and chemotherapy-induced nausea (FA2020 p400)

Give mesna with cyclophosphamide to prevent hemorrhagic cystitis (FA2020 p251)

Sildenafil is a PDE5 inhibitor that runs the risk of causing hypotension in patients on nitrates due to the synergy of the mechanisms of action. [FA2020 p246]

Nitrates, like nitroglycerin, work by increasing NO production which in turn acts to increase cGMP in smooth muscle causing vasodilation. PDE5 inhibitors act by decreasing the breakdown of cGMP in smooth muscle, enhancing the action of NO to cause vasodilation. Thus, when combined there can be systemic vasodilation that leads to dangerous hypotension.

For diabetic nephropathy (as evidenced by her microproteinuria), ACE inhibitors or angiotensin receptor blockers (-sartans, such as irbesartan) are first line for preventing progression of the disease. They also help to further control blood pressure. Thus, an ARB would be the best choice of the answers given.

Peutz-Jeghers syndrome is an autosomal dominant syndrome associated with hyperpigmented macules on the mouth, lips, hands, and genetalia as well as increased risk of breast and GI cancers. [FA2020 p387]

This patient presents with the characteristic hyperpigmented macules as well as positive occult blood test which could be indicative of an underlying GI malignancy. Peutz-Jeghers is also associated with numerous hamartomas throughout the GI tract which could be associated with the patient's general GI symptoms due to their ability to cause blockage.

Other answers:

• Cowden disease - multiple hamartoma syndrome that increases risk of breast, thyroid, uterine, and other cancers; it is not associated with the hyperpigmented macules
• Gardner syndrome - familial adenomatous polyposis + osseous and soft tissue tumors
• Muir-Torre syndrome - rare hereditary autosomal dominant cancer syndrome thought to be a subtype of HNPCC (Lynch syndrome)
• Neurofibromatosis - not associated with GI issues and typically have a very different presentation (FA2020 p525) - NF1 = cafe-au-lait spots, lisch nodules, pheochromocytoma, seizures, cutaneous neurofibromas, etc.; NF2 = bilateral vestibular schwannomas, juvenille cateracts, meningiomas, ependymomas

Removal of the spleen makes individuals more susceptible to encapsulated bacterial infection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenza, etc). Thus you can eliminate all but two answers.

Streptococcus pneumoniae is the most common cause of viral meningitis in individuals 6months to 6 years and over 60 years old. It is the second most common cause (after Neisseria) in individuals 6-60years.

Our patient is 55. Of the answer choices given, S. pneumoniae would be the most likely cause of her meningitis.

The combination of "stairs, chairs, and hair" symtoms of proximal myopathy, dermatologic symptoms (rash) and positive antinuclear antibody (ANA) makes dermatomyositis the most likely diagnosis [FA2020 p471].

The other autoimmune conditions listed (which could be associated with ANA) are not likely to have the same muscular involvement. Myscular dystrophy does not have dermatologic involvement or ANA+.

Atrial myxomas are the most common cardiac tumor in adults (FA2020 p316).

Myxomas can cause "ball-valve" obstruction in the left atrium associated with syncopal episodes. Myxoma is a myxoid tumor of primative connective tissue and is composed of myxoma cells in a gelatinous glycosaminoglycan matrix. Thus, the description of a heterogenous pedunculated mass would fit.

Aarterial emboli can associated with myxomas, though none occurred in this patient.

Polyarteritis nodosa is a medium vessel vasculitis associated with different stages of transmural inflammation with fibrinoid necrosis of vessels. [FA2020 p314]

Because this is a vasculitis that affects medium vessels, it can affect the arteries supplying the muscles and thus cause segmental ischemic necrosis from loss of blood supply.

This is eclamsia because of the hypertension in pregnancy with symptoms of end-organ damage and failure combined with siezures (FA2020 p643).

None of the other answers are consistent with the presentation. Epilepsy alone does not cause the symptoms of end organ damage (elevated liver enzymes, lactate dehydrogenase, and inability to urinate), renal disease alone likewise would not cause the combination of symptoms. Sepsis and septic shock causes hypotension not hypertension as seen in this patient. There is no specific drug toxidrome that matches the combination of symptoms.

Prostatic carcinoma commonly metastasizes to bone and forms osteoBLASTIC lesions (different than most cancers that cause ostroclastic lesions) [FA2020 p223]

Small cell lung cancer can also cause osteoblastic lesions, but much less commonly and it would likely be associated with other symptoms/paraneoplastic syndromes.

Giant granules in neutrophils and eosinophils combined with immunodeficiency (recurrent infections) and partial albinism is characteristic for Chediak-Higashi which is caused by defect in the lysosomal trafficking regulator gene [FA2020 p116]

Hairy cell leukemia is notable for staining tartrate-resistant acid phosphatase positive (TRAP positive) and for having hairy cytoplasmic projections [FA2020 p432].

If you did not know this, you could eliminate other answers based on the stem:

• Lymphomas would have swollen lymph nodes
• It mentions the lymphocytes as the issue and he has lymphocytosis, so you can eliminate the myelogenous leukemias and focus on the ones from the lymphocytic cell lines
• Acute lymphoblastic leukemia most commonly occurs in children and is associated with immature B/T-cells that are TdT+, so you can eliminate this
• Chronic myelogenous leukemia is slowly progressing and associated with smudge cells, so it also does not match the descriptors.

This man has gout, and acute attacks of gout can be triggered by alcohol consumption as alcohol metabolites compete for excretion with uric acid in the kidney (FA2020 p467). Uric acid levels can be normal during acute attacks (as in this patient).

Tobacco use is a major risk factor for pancreatic adenocarcinoma (FA2020 p398).

Diabetes is also a major risk factor but carries less of a risk than smoking.

FA2020 p225 also has a list of carcinogens and associated cancers.

This is Wegener's granulomatosis (granulomatosis with polyangiitis) for the following reasons: (FA2020 p314)

• Recurrent sinusitis, perforation of nasal septa, pulmonary nodules - symptoms of Wegener's
• PR3-ANCA = antibodies against proteinase 3, this is the primary clue and requires that you know that anti-PR3 is the same thing as c-ANCA which is characteristic of Wegener's

She has a microcytic anemia with no major symptoms, normal vital signs, no history of illness, and normal other cell counts. Of the answers, iron deficiency anemia is the only one that fits that description and makes sense because she is a premenopausal woman (women are at risk of iron deficiency anemia due to monthly bleeding).

Aplastic anemia would have low platelets and leukocytes as well. Sickle cell and thalassemia would lokely present with a hemolytic anemia and jaundice or some other symptoms (plus they are present from birth). B12 deficiency is megaloblastic anemia and has neurological symptoms.

This is acute pericarditis (FA2020 p313) for the following reasons:

• Pain exacerbated by inspiration and decreased by leaning forward
• Friction rub (harsh scratchy sound present in both systole and diastole)
• Associated with rheumatoid arthritis (autoimmune conditions are associated with fibrinous pericarditis)
• No true pulsus paradoxus (pulsus paradoxus is >10mmHg decrease in systolic blood pressure during inspiration and is associated with cardiac tamponade though it can be seen in consrtrictive pericarditis as well)

Here is a diagram of the listening locations for each valve/heart murmur.

This is aortic stenosis because they are listening over the aortic area and it is a systolic murmur. Rationally, it makes sense that aortic stenosis is systolic because in systole you would be attempting to push blood out through a stenotic valve and it would cause a murmur.

Likewise, aortic regurgitation is in diastole because it is during relaxation of the ventricle that the blood will be regurgitated back from the aorta to the ventricle causing a murmur.

FA2020 p290-291

She has osteoporosis which has led to compression fracture. Postmenopausal women are at highest risk due to age and decreased estrogen levels (estrogen withdrawal). [FA2020 p462]

Ironically, smoking is not as strong of a risk factor as female gender and postmenopause.

The prostatic plexus of the pelvic splanchnic nerves is in close proximity to the prostate and risks damage.

This is mesenteric artery stenosis causing postpranidal intestinal ischemia/angina. I definitely did not know this answering the question and I personally got to the answer by attempting to logically think through the symptoms:

• Weight loss and abdominal pain in general pointed to intestinal ischemia of some sort and since most absorption of nutrients happens in the jejunum, ischemia there would cause weight loss. Jejunum is supplied by SMA
• Bruit to me meant a larger vessel was blocked since to be able to hear it it has to be a pretty large vessel, SMA is one of the larger arteries listed
• No liver symptoms (i.e. jaundice) so eliminated hepatic artery

If anyone has a better explanation please offer it.

Plasmodium vivax/ovale have a dormant hypnozoite form which infects the liver and can remain dormant. This is why P. vivax/ovale must be treated with primaquine on top of chloroquine (because only primaquine can kill the hypnozoites in the liver) [FA2020 p157]

An additional important fact, Plasmodium vivax/ovale have the "tertian" (48-hour) fever cycle on the first and third day.

NOTE: You would also NOT want to use chloroquine to treat P. falciparum because resistance is too high among that species. However, this is not the reasoning given in the question.

This boy has DiGeorge Syndrome (CATCH22) due to failure of development of the 3rd and 4th pharyngeal pouches: [FA2020 p116]

• Cardiac defects (conotruncal abnormalities)
• Abnormal facies
• Thymic hypoplasia/aplasia (leading to T-cell deficiency and immunodeficiency)
• Cleft palate (our boy does not have but it is common)
• Hypocalcemia (due to agenesis/aplasia of the parathyroid glands
• 22q11 microdeletion

Vinblastine works by binding tubulin and inhibiting microtubule formation. This inhibits cell division.

Basically, this question is asking which of the following cell types is nondividing/would not need functioning microtubules.

Enterocytes in crypts (which divide to replace intestinal epithelium(, keratinocytes of the stratum basale (which divide to to replace skin), and erythroblasts (blasts are stem cells) are all dividing cells and thus could be affected by vinblastine. Cortical thymocytes are also dividing cells, as they will divide to create progeny T-cells through the process of T-cell maturation.

Thus, the only non-affected cell is ventricular cardiomyocytes.

Blue sclera and multiple fractures is indicative of ostoegenesis imperfecta (brittle bone disease), which is caused by defect in collagen synthesis due to an error in procollagen formation (FA2020 p50 and 51). There are multiple types that vary in severity.

En FU virtide is a ... FU sion inhibitor.

Binds gp41 and inhibits fusion and entry of the virus.

The key here is this man has no history of bleeding problems yet he has an extremely prolonged PTT (associated with the intrinsic coagulation cascade pathway). This is suggestive that he is deficient in the "unnecessary" factor of the intrinsic pathway, factor XII. (FA2020 p412)

Factor XIIa (Hageman's factor) of the intrinsic pathway activates prekallikrein to kallikrein.

Histamine release, phagocytosis, and C5a generation are not associated with the intrinsic coagulation cascade. Platelet aggregation impairment could be associated with increased PTT (i.e. vWF deficiency, p428), but not that extreme of prolongation without symptoms of bleeding issues.

Fragile X syndrome is X-linked dominant inheritance associated with a trinucleotide repeat in FMR1 (FA2020 p62).

Even if you did not know this fact, fragile X syndrome (a disease affecting the X chromosome) should be X-liked of some sort.

Knowing the disease is X-linked, you can get to the answer because in the couple, the father is the only one with a family history of the disease. Whether the disease was X-linked recessive or X-linked dominant, if the father had the diseased X-chromosome he would have the disease (as males only have one X chromosome). Since the father does not have the disease, he does not have the chromosome and thus cannot pass it on. Thus, the chance of their child having the disease is 0%

Bartonella henslae is transmitted by cat bite/scratch and can lead to cat scratch disease which presents with a red bump on the skin, fatigue, discomfort, and swollen lymph nodes draining the injury. (FA2020 p149)

Of the answers, toxoplasma gondii can also be spread by cats (cat feces), but in otherwise healthy people it causes a mono-like illness and would not have skin manifestations.

This boy has cystic fibrosis, which is caused by a defect in the CFTR gene which codes for an ATP gate chloride channel. The most common mutation leads to a misfolded protein (defect in protein structure) that results in the protein being retained in the RER and not transported to the cell membrane. (FA2020 p60)

-alol and -ilol (i.e. labetalol and carvadilol) are nonspecific blockers of alpha and beta receptors. (FA2020 p245)

• Hydralazine increases cGMP and causes smooth muscle relaxation via vasodilation. It is used in acute hypertension and is safe to use in pregnancy.
• Phenoxybenzamine is an irreversible nonspecific alpha blocker used pre-surgically in pheochromocytoma.
• Phentolamine is a reversible nonspecific alpha blocke given in some cases of severe acute hypertension such as for hypertensive crisis from MAOis.
• Trimethaphan is a blocker of the presynaptic nicotinic AcH receptors for both the sympathetic and parasympathetic nervous systems.

B labels the spleen, which is removed in ITP because the splenic macrophages are responsible for phagocytosing platelets (FA2020 p427)

Renal papillary necrosis is a common complication of sickle cell disease which would cause gross hematuria (FA2020 p602, p422).

Glomerulonephritis would be associated with RBC casts rather than gross hematuria (casts are present if they are released from the glomerulus or tubules). Nephrolithiasis (kidney stones) are not associated with sickle cell and would likely be associated with crystals of some sort on urinalysis. Prostatitis would likely present with more WBCs and does not commonly present with hematuria but rather urgency and dysuria. Transitional cell carcinoma is rare in the kidney and transitional cell carcinoma of the bladder is associated painless hematuria.

The superior mesenteric artery supplies the distal duodenum to the proximal 2/3 of the transverse colon, so the jejunum is within its territory (FA2020 p364). None of the other answers are in the SMA territory.

This man presents with classic features of Parkinson Disease which is caused by degeneration of dopamine producing neurons in the substantia nigra (FA2020 p520)

The description points toward small cell carcinoma of the lung (a small blue cell tumor, FA2020 p684, 228)

Small cell lung cancer has a very high association with ectopic ADH secretion as a paraneoplastic syndrome. Ectopic secretion of ADH (SIADH, p338) leads to hyponatremia primarily by increased volume and subsequent inhibition of the RAAS (renin-angiotensin-aldosterone system) which causes loss of sodium.

The facial nerve exits the skill via the internal acoustic meatus where it will traverse through the inner ear cavity (FA2020 p505 and 506). The facial nerve also innervates the muscles of facial expression and thus would cause her ipsilateral facial weakness (facial nerve lesions p532).

"Vincristine crisps the nerves" (FA2020 p441)

Vincristine is a common cause of chemotherapy-associated peripheral neuropathy (with cisplatin also having an association with neuropathy but not being used for breast cancer). Vincristine acts by binding tubulin and inhibiting microtubule polymerization. This affects cancer cells by inhibiting division, but also affects axons by inhibiting axonal transport.

This question can be answered by a process of elimination approach in my opinion: (FA2020 p638)

• Because he has testes that formed, he has to have the SRY gene and thus the Y chromosome which eliminates 46,XX and 47,XXX.
• This is not a normal-looking biopsy and the question asks about a chromosomal abnormality so you can eliminate 46,XY.
• Mosaic karyotype 45,X/46,XY is associated with Turner's syndrome. These individuals present with female external genetalia and testes undescended or rarely descended into the labia majora. They would not have scrotal testes, and thus this eliminates this answer.

This leaves only 47,XXY which is Kleinfelter's syndrome and is associated with testicular atrophy and extensive fibrosis and hyalinization leading to infertility.

Neural crest cells migrate to form the aorticopulmonary septum and abnormalities associated with neural crest migration in the heart include tetrology of fallot, transposition of the great arteries, and persistent truncus arteriosus. Fusion of the aorticopulmonary septum with the muscular ventricular septum is what forms the membranous septum, so patients with a persistent truncus arteriosus will have VSD as well. (FA2020 p280)

I think this is Strongyloides stercoralis (threadworm) is a roundworm whose larvae live in soil and who can cause pulmonary disease. It has the ability to penetrate skin from the soil but can also be obtained by ingesting feces contaminates soil (FA2020 p159) https://www.cdc.gov/parasites/strongyloides/gen_info/faqs.html

Most intestinal roundworms are fecal-oral route except strongyloides which can also penetrate skin, hookworm (necator americanus) which only penetrates skin, and trichinella which can come from undercooked meats (especially pork) but whose symptoms do not match that of the patient. Trichinella larvae enter the blood stream and infect muscle and can also cause trichinosis with fever, nausea, vomiting, periorbital edema, and myalgia.

This woman's history is characteristic of multiple sclerosis (FA2020 p 523) which is a demyelinating disorder of the CNS. Oligodendrocytes make up the myelin sheathes in the CNS and are attacked in multiple sclerosis.

This is MS because:

• Acute optic neuritis is characteristic (painful loss of vision)
• Pyrimidal tract demyelination with spasticity and weakness is characteristic
• Oligoclonal banding in CSF and T2 weighted lesions in white matter on MRI are diagnostic

Even if you did not get MS from the stem, the white matter lesions point you to specifically myelinated lesions, and the oligodendrocytes make up myelin sheaths in the CNS.

First order elimination: a constant FRACTION of drug is metabolized per unit time (i.e. elimination rate is proportional to the drug concentration)

This differs from zero order elimination where a constant amount of drug is metabolized per unit time (i.e. rate stays constant)

In this question:

• In two hours, 2.5 mg of 12.5 mg is metabolized, which is a fraction of 2.5/12.5 = 0.2 or 20%
• Thus, in another two hours, another 20% will be metabolized since this is first-order elimination
• 20% of 10 is 2 and 10-2 = 8

FA2020 p232

This man is presenting with the classic findings of vitamin B12 deficiency: megaloblastic anemia (anemia and high MCV) with neurologic findings. (FA2020 p69 [nice])

B12 requires intrinsic factor in order to be absorbed appropriately. Intrinsic factor is made by parietal cells of the stomach.

Orchiectomy will remove the testosterone stimulus prostatic cancer cells are dependent upon for growth and division. With removal of this stimulus, the cells will undergo apoptosis (scattered shrunken cells are apoptotic bodies).

The other answers are unlikely:

• Corpora amylacea are small hyaline masses in the prostate gland of unknown significance. It would not be a change from normal to find these.
• Edema is unlikely as this is more characteristic of diseases like prostatitis where inflammatory cytokines cause leaky blood vessels. Orchiectomy would not cause prostatic inflammation.
• There is no stimulus for hypertrophy and rather with orchiectomy you are removing a growth stimulus.
• Necrosis of the blood vessel walls is not likely because the blood vessels are not affected by the loss of the androgens, rather the actual prostatic cells are.
• Widespread necrosis is also not likely as this is not the mechanism of death after testosterone removal (death will occur by apoptosis rather than necrosis) and widespread necrosis is more characteristic of infarct or something that causes massive sudden tissue death.

This is anesthesia being given via lumbar puncture. [FA2020 p507]

The needle will pass through the supraspinous ligament, intraspinous ligament, and ligamentum flavum before entering the epidural space.

The anterior longitudinal ligament is on the anterior side of the spinal cord. The costotransverse would not be punctured. Image of the anterior longitudinal and costotransverse spinal ligaments here.

The denticulate ligament is what holds the pia mater to the dura mater. Since this is likely epidural anesthesia it would not be punctured.

The posterior longitudinal ligament is on the posterior portion of the vertebral body but is anterior to the spinal cord, and thus would not be punctured.

The blood:gas partition coefficient is the ratio of concentration of anesthetic in the blood vs. in the lungs when a steady state is reached. Blood/gas partition coefficient is an expression of solubility of the drug in plasma, and less soluble agents have a faster onset/offset.

MAC (minimum alveolar concentration) is the concentration of anesthetic in the lungs where 50% of the population does not move in response to a surgical srtandard stimulus. It is analogous to ED50 in other areas of pharmacology. MAC is increased with decreasing solubility (decreaseing blood/gas partition coefficients) and decreased potency. If you think about it this would make sense because if a drug is less soluble or not as potent, you have to administer more of the drug and thus would have to have a higher minimal alveolar concentration to see an effect. [FA2020 p549]

NOTE: MAC is additive so if you mix two gases at 0.75% of their MACs, you get a total 1.5% MAC. Thus for the question, you are essentially administering the same TOTAL MAC to each group, so it is not the difference in MAC that is causing the difference observed.

The brain:gas partition coefficient, more commonly called the oil:gas partition coefficient, is used as a surrogate for the amount of anesthetic in the brain and corresponds to lipid solubility. CNS drugs must be lipid soluble or actively transported. As these are inhlaed anesthetics, the lipid solubility actually does not greatly contribute to time of onset/offset; instead the plasma solubility is the limiting factor. Oil/gas partition coefficient would be associated with the drug potency.

Sublingual nitroglycerin is commonly given to relieve anginal pain as described. The MOA of nitroglycerin is vasodilation by increasing NO release which subsequently increase cGMP in smooth muscle, causing relaxation (FA2020 p318).

NADPH oxidase initiates the respiratory burst (FA2020 p109) which is vital for appropriate intracellular killing of phagocytosed organisms.

Nocardia is a gram(+), weakly acid-fast bacteria that forms long, branching filaments resembling fungi. (FA2020 p139). Nocardia commonly causes pulmonary infection in the immunocompromised.

For the other answers: Fungi would not be gram (+) so you could eliminate Candida. Pneumocystis is "dented ping pong balls" and not filamentous on bronchoscopy. StreptoCOCCUS is a gram(+) coccus, not a rod. Bacillus anthracis is a gram(+), spore-forming rod that can have "medusa-head" halo of projections but his history does not have an exposure that would point to pulmonary anthrax (wool-sorters disease) and further it would still not be described as filamentous. Pulmonary anthrax also would likely have widened mediastinum on CXR.

This man has HSV meningitis. The treatment of choice is acyclovir/valacyclovir which are guanosine analogs which preferentially inhibit viral DNA polymerase by chain termination (FA2020 p201). Cidofovir also preferentially inhibits viral DNA polymerase and is used for acyclovir-resistant HSV. Foscarnet is also a viral DNA/RNA polymerase inhibitor used for acyclovir-resistant HSV.

Remember HSV are DNA viruses (HHAPPPPy) (p163)

Other answers:

• Neuraminadase inhibitors (oseltamivir[tami-flu], zanamavir) are used for influenza
• Protease inhibitors are used for HIV (-navir) and hepatitis C (-previr)
• Reverse transcriptase inhibitors are used for HIV (NNRTIs and NRTIs). Foscarnet is technically also a reverse-transcriptase inhibitor but is used for acyclovir resistant HSV.
• RNAase A inhibitor is not a viral treatment

Prader-Willi syndrome occurs due to a defect in the paternal chromosome 15 which causes issue because of imprinting that occurs silencing the maternal chromosome. If there is not a functioning paternal allele, any maternal allele will be silenced leading to lack of a functional copy of the alleles and disease.

Imprinting is when certain alleles are expressed differently depending on which parent they are inherited from. Genes are silenced specific to either maternal or paternal origin, and therefore only one allele is expressed. If the NON-silenced gene is dysfunctional or absent, then there will not be expression of a functioning allele, and thus disease results.

The two primary disorders of imprinting are P rader-Willi (caused by dysfunctional Paternal chromosome 15) and Angel M an (caused by dysfunctional Maternal UBE3A on chromosome 15).

In this individual, he has Prader-Willi syndrome but does not have the customary deletion on the arm of chromosome 15. Remembering in Prader-Willi that the paternal chromosome is typically dysfunctional and the maternal genes are silenced, it can be assumed that in order to have the disorder he had two copies of the maternal chromosome and both were silenced, producing a functional deletion even though he does not have the actual deletion.

Another way of thinking of this is the genes that prevent Prader-Willi will always be silenced on maternal chromosomes, so even if he has normal maternal chromosomes he will have a lack of function and thus Prader-Willi syndrome unless he has a normal paternal chromosome.

Syringomyelia (syrinx) is known for causing loss of pain and temperature sensation as one of the first symptoms due to the damage of the anterior white commisure of the spinothalamic tract (FA 2020 p530, p492)

The description of the loss of sensation of pain and temperature to both upper extremities as well as to a portion of the trunk describes the characteristic "cape-like" distribution.

Type II pneumocytes secrete surfactant from lamellar bodies (FA2020 p661)

Premature infants are at risk for neonatal respiratory distress syndrome due to inadequate production of surfactant.

A continuous, machine-like murmur is characteristic of a patent ductus arteriosus (FA2020 p291, p298)

The patency of the ductus arteriosus is maintained by prostaglandins (hence why newborns who need to keep a patent ductus arteriosus due to other heart defects are put on prostaglandin drips).

In this newborn's case, the patent ductus arteriosus is not necessary (there are no signs of additional heart defect that would necessiate it) and thus we want to close it.

To close a PDA, we would want to inhibit prostaglandins somehow, and cyclooxygenase inhibitors (NSAIDs) inhibit the production of prostaglandins and thus would speed up closure of the ductus arteriosus. IV indomethacin or ibuprofen are most commonly used to close the PDA.

Though inhibition of phospholipase A2 by corticosteroids would also serve to inhibit production of prostaglandins, this is more nonspecific and could be associated with more unwanted side effects. Coritcosteroids in a newborn are more often used for neonatal respiratory distress syndrome to elicit production of surfactant.

The first-line treatment for acute management of deep venous thrombosis is unfractionated or low-molecular weight heparin. The MOA of heparin is binding to and potentiation of the action of antithrombin III. (FA2020 p671, p436)

Here is a diagram showing the coronary arteries.

Important related facts to remember:

• LAD (left anterior descending) comes off left coronary - LAD is blocked in anterior infarctions
• LCX (left circumflex) comes off left coronary and the left marginal artery comes off the LCX - LCX is blocked in lateral infarctions and some posterior (if left dominant)
• Right coronary artery supplies the entire right side of the heart and gives rise to the right marginal artery - RCA is blocked in most posterior infarctions and infarctions affecting the right ventricle
• Which artery gives rise to the posterior descending artery determines the "dominance" of the heart - PDA from the RCA is right dominant [right dominant is most common], PDA from the left circumflex is left dominant

Also found FA2020 p283

Cystic fibrosis commonly leads to pancreatic insufficiency and thus impaired absorption of the fat soluble vitamins (ADEK). Vitamin E can cause demyelination fo the posterior columns and spinocerebellar tract (FA2020 p60, p70)

Vitamin E deficiency can appear similarly to vitamin B12 deficiency due to the neurologic effects appearing similar, but the history of cystic fibrosis points to fat soluble vitamin E deficiency. Further, B12 deficiency is not a choice.

• Folic acid (B9) deficiency causes megaloblastic anemia and does not cause neurologic symptoms. Deficiency can be caused by phenytoin, methotrexate, or sulfonamides. Deficiency in pregnancy is associated with neural tube defects.
• Vitamin A deficiency causes night blindness, dry skin, squamous metaplasia, corneal degeneration, and immunosupression.
• Vitamin B6 (pyridoxine) deficiency causes sideroblastic anemia, convulsions, hyperirritability, and peripheral neuropathy. Deficiency is commonly associated with isoniazid.
• Vitamin D deficiency causes rickets in children and osteomalacia in adults (both bone issues) as well as hypocalcemia and associated hypocalcemic tetany.

Right lung because the right main stem bronchus is more vertical and slightly wider and lower lobe because of gravity

This can also be thought of similarly to where abscesses from aspiration will be found (FA2020 p685) - most typically right for the reason mentioned above; lower lobe if upright and middle or upper posterior segments if lying down on their back.

Here is a slide/explanation with a diagram:

https://i.paste.pics/7f64029bdc3b54306b1fa674a380170f.png

Cranial nerve and vessel pathways FA2020 p505

"Standing room only" for the pathways of V1, V2, and V3

• V1: Superior orbital fissure
• V2: Foramen rotundum
• V3: Foramen ovale

Microglia are phagocytic cells and are responsible for clearing debris/necrotic tissue as well as releasing inflammatory mediators (FA2020 p493)

• Astrocytes are the most common glial cell in the CNS and are responsible for generation of the blood brain barrier as well as for reactive gliosis in damage (FA2020 p493)
• Important things to know about the neuron reaction to damage would be that the cell body undergoes chromatolysis after axonal injury and distal to the site of injury the axon undergoes Wallerian degeneration. (FA2020 p495)
• Oligodendrocytes are the myelin sheath forming cells of the CNS.
• Satellite cells are basically the peripheral nervous system version of astrocytes and have a supportive nutritive function in the PNS.

This is goodpasture syndrome which has antibodies directed against alveolar and glomerular basement membranes (FA2020 p596)

The key hints are:

• Lung involvement
• Crescent formation (indicating rapidly progressive "crescentic" glomerulonephritis)
• "Linear" deposits of IgG and C3 - this is characteristic of Goodpasture because the antibodies are to the glomerular basement membrane so they deposit all along the glomerulus basement membrane leading to linear immunofluorescence.
• Remember that the other main lung/kidney combination, granulomatosis with polyangiitis, is Pauci immune with no immunofluorescence and they will usually mention ANCA

Li Fraumeni syndrome is associated with a loss of function mutation in p53 (FA2020 p224, p46)

p53 is a modulator at the G1/S restriction point. p53 activation in the presence of DNA damage, misfolded protein, and hypoxia leads to activation of BAK/BAX and subsequent activation of the apoptotic pathway (p208). Thus, loss of function of p53 will lead to impaired regulation of apoptosis and uninhibited cell division in cancer cells.

Li Fraumeni syndrome is associated with multiple tumors at a young age (SBLA - sarcoma, breast, leukemia, adrenal)

In eukaryotes, the 5' methylguanosine (m7G) cap is important in the initiation of translation because eukaryotic initiation factors (eIFs) identify the cap and help assemble the ribosome at that site (FA2020 p45).

The absence of a 5' m7G cap would thus require a different sequence to allow translation initiation and ribosomal entry (i.e. an internal ribosomal entry site).

The 5' and 3' untranslated regions are more important in regulation of translation and termination of translation, respectively, and their absence would not aid translation of the viral mRNA. The 3' poly-A tail is important for protection of eukaryotic mRNA from degradation and aiding in exportation from the nucleus; its absence would not aid translation. A very short open reading frame would not make a significant difference in ability to be translated (the open reading frame is the part of the mRNA able to be translated).

This is metastatic renal cell carcinoma (FA2020 p605) for the following reasons:

• Polycythemia - this is the primary clue, as it is associated with ectopic EPO (erythropoitin) secretion in paraneoplastic syndromes (FA2020 p228), which can be caused by pheochromocytoma, renal cell carcinoma, heptocellular carcinoma, hemangioblastoma and leiomyoma. Of these, only liver and kidney would be a choice given and hepatocellular carcinoma is incorrect because he did not have any associated finding of jaundice, hepatomegaly, ascites, or anorexia (FA2020 p392). Plus, the liver does not commonly metastasize to brain whereas kidney does (FA2020 p223)
• Hypercalcemia - this is likely indicative of PTHrP secretion, and renal cell carcinoma is one of the cancers that can do this. However, this is fairly nonspecific as there are many cancers that can secrete PTHrP.
• Heamaturia - suggestive of kidney/urinary tract involvement
• Negative for carcinoembryonic antigen - this is a nonspecific marker mainly for colon and pancreatic cancers (FA2020 p226)

The colon from the splenic flexure to upper rectum drain to the inferior mesenteric lymph nodes (FA2020 p97).

You can remember this because this is a part of the hindgut which is supplied by the inferior mesenteric artery.

NOTE: The anal canal has different lymphatic drainage that is worth noting (FA2020 p366) - above the pectinate line and lower rectum drains to the internal iliac lymph nodes and below the pectinate line drains to the superficial inguinal lymph nodes.

Yellow nodules (cholesterol deposits) on the achilles tendons have a very high association with Type II familial dyslipidemia, or familial hypercholesterolemia. This is caused most often by a defect in the LDL receptor function. (FA2020 p94)

The description of "spindle cells arranged in small cluseters" with amyloid staining as well as the mention of C-cells (which secrete calcitonin) points to a medullary thyroid carcinoma which commonly secretes calcitonin. (FA2020 p343)

Though this was not asked and not required to answer the question, she also has a history of pheochromocytoma which points to her having one of the MEN2 syndromes, as MEN2A and MEN2B are both associated with pheochromocytoma and medullary thyroid carcinoma! (FA2020 p351)

Thymoma is most commonly associated with myasthenia gravis as a paraneoplastic syndrome (FA2020 p228)

Myasthenia gravis is characterized by antibodies to the acetylcholine receptor and commonly presents with ptosis, diplopia, and ophtalmoplegia [p472]

FA2020 p256

This would be a prospective cohort as they are looking at two groups with and without risk factors and assessing disease incidence.

UWorld has a super pretty picture which helps visually explain the differences (Copyright UWolrd, blah blah buy UWorld)

In a normal distribution, one standard deviation on either side of the mean will contain 67% of the data set (68-95-99 rule).

FA2020 p262

FA2020 p258

Odds ratio = (250/250) / (50/150) = 3

• Clinical trial Phase I - healthy volunteers asking is it safe [FA2020 p256]
• Phase II is small # people with the disease - does it work, optimal dosing, side effects?
• Phase III is larger # with disease - is it good or better? (randomized controlled trial phase)
• Phase IV - postmarketing surveillance

The centripetal rash (beginning on the extremeties and spreading to the trunk) is characteristic of Rocky Mountain Spotted Fever caused by Ricketsia rickettsii whose vector is a tick. It presents with headache, fever, and rash. The treatment for all of the Rickettsial illnesses is doxycycline. (FA2020 p150)

Thiazide diuretics can cause hypokalemia (FA2020 p609).

The question stem is referring to a conjugate vaccine. This is because conjugate vaccines convert T-independent antigens (polysaccharides) into T-dependent antigens by conjugating them with a protein. [FA2020 p127]

Remember that in order for a T-cell to be able to respond to an antigen via MHC, it MUST be a protein. Thus, T-dependent (dependent on T-cells) responses are to proteins. T-dependent responses are overall better because then B-cells can then undergo affinity maturation and class switching through interaction with T-cells. So, by conjugating bacterial polysaccharides to proteins, the immune response will be a more robust T-dependent reaction and will yield better protection. [FA2020 p103]

Conjugate vaccines exist for encapsulated bacteria (as the capsules are polysaccharide and would need to be conjugated to protein to improve response). These are Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae

You can remember these encapsulated organisms and their conjugate vaccine because they are THE SAME organisms that you become susceptible to when you have a splenectomy and which necessitate vaccination.

This has to do with the algorithm of treating shock. Septic (a type of distributive) shock as well as hypovolemic shock are treated with IV fluid resuscitation (FA2020 p310). Crystalloid fluids are first-line choice, and normal saline (0.9%, isotonic) is first-line specifically in cases of shock.

5% dextrose in water and 0.45% saline is hypertonic and not useful here.

5% dextrose alone is isotonic in the bag but physiologically hypotonic. It is more often given for fluid replacement after severe dehydration.

0.45% saline only is hypotonic and not useful here.

3% saline is hypertonic and not useful here.

• Here is a chart of the fluid resuscitation for the different kinds of shock
• Here is a chart of the different kinds of IV solutions and in general when to use them
• Here is another chart of IV solutions and uses cause I like charts
• And here is an image showing in general when to give normal saline (0.9% saline)

Spironolactone has a special use in hepatic ascites (FA2020 p609).

Spironolactone is the drug of choice for initial treatment of ascites due to cirrhosis

The big hint here is EXTREME respiratory depression which is characteristic of opioid overdose, so he should be given naloxone. [FA2020 p570 has drug intoxication and withdrawal syndromes]

Ibutilide is a Class III antiarrhythmic drug. Most Class III antiarrhythmics are associated with Torsdaes de Pointes as a complication [FA2020 323]

Other drugs associated with Torsades de Pointes are drugs that induce prolonged QT including: Class IA antiarrhythmics, some antibiotics like macrolides, antipsychotics like haloperidol, TCAs, and some antiemetics like ondansetron [FA2020 p294].

Loratadine is a second generation antihistamine and thus would be preferred in this patient as it does not cause sedation. [FA2020 p686]

Since he works operating heavy machinery, it would be preferred to put him on a second generation antihistamine. Bropheniramine, hydroxyzine, and diphenhydramine are first generation antihistamines which cause sedation.

Ranitidine is a histamine H2 blocker used to decrease secretion by parietal cells in peptic ulcer disease, gastritis, and gastric reflux [FA2020 p399]

Aminoglycosides (like gentamycin) are bactericidal via irreversible inhibition of the initiation comblex by binding the 30S subunit [FA2020 p191]

• Amoxicillin is a beta-lactam antibiotic which works by binding and inhibiting penicillin-binding proteins (transpeptidases) and block cross-linking in the cell wall [p187]
• Ciprofloxacin is a bactericidal fluoroquinolone which acts by inhibiting DNA gyrase (topoisomerase II) and topoisomerase IV [p195]
• Erythromycin is a macrolide (the macrolides are ACE - azithromycin, clarithromycin, and erythromycin) which acts by inhibiting protein synthesis via bindind to the 50S subunit and preventing translocation (macroslides) [p193]
• Sulfamethoxazole is a sulfonamide which acts by inhibiting dihydropteroate synthase therfore inhibiting folate synthesis [p194]

Omeprazole is a proton pump inhibitor which affects the bioavailability of itraconazole presumably by interfering with absorption as it decreases gastric pH.

https://www.ncbi.nlm.nih.gov/pubmed/9626921

https://www.ebmconsult.com/articles/ppi-proton-pump-inhibitors-decrease-absorption-itraconazole

A postinfarction fibrinous pericarditis can occurs 1-3 days after MI [FA2020 p307 has post-infarction complications and the days they are associated with].

Also, friction rubs are characteristic of pericarditis.

Terminal complement deficiencies (C5-C9) are associated with recurrent Neisseria infection [FA2020 p107]

This woman likely has endometriosis, characterized by cyclic pelvic pain, bleeding, and associated with infertility (FA2020 p648). It is associated with "chocolate cysts" on the ovaries. Proliferative endometrial tissue would be found on biopsy

Endometriosis scar tissue/adhesions can cause the uterus to stick in a backwards position (retroverted) according to https://www.healthline.com/health/womens-health/tilted-uterus

Polycystic ovarian syndrome is associated with obesity would also likely have symptoms of hisutism and acne as well as infertility. It also presents with amenorrhea or oligomenorrhea. [FA2020 p645]

This man has SIADH (syndrome of inappropriate antidiuretic hormone) which is likely caused by a paraneoplastic syndrome associated with small cell lung cancer (FA2020 p228)

This man presents with hyonatremia, hypochloremia, normal potassium, normal BUN and creatinine, decreased plasma osmolality, and increased urine osmolality. SIADH is characterized by urine osmolality>serum osmolality and hyponatremia (p338). This is because ADH triggers retention of water by insertion of awuaporins into the collecting tubules. The increased body water triggers decreased secretion of renin and decreased activation of the renin-angiotensin-aldosterone system. Less aldosterone leads to less retention of sodium and less excretion of potassium. This combined with dilution from retention of water leads to hyponatremia with potassium normal. BUN/creatinine are unaffected because the kidneys are undamaged.

This is NOT ectopic ACTH secretion because that would lead to Cushing's syndrome which does not have the characteristic osmolality differences and increased cortisol can mimic mineralocorticoids leading to hypernatremia.

This is feedback inhibition of the RAAS (renin-angiotensin-aldosterone system) axis. Increased aldosterone will feedback and inhibit renin secretion of the kidney. (FA2020 p588)

In agreement with the other post: (see FA2020 p331)

You would want to check FREE T4 because pregnancy increases Thyroid binding globulin. It is possible she might have increased overall T4, but NOT have hyperthyroidism because the free T4 is normal (i.e. her increases amount of thyroid binding globulin has bound more T4, and since our bodies respond to the concentration of free T4 only, the hypothalamus should ensure that the free T4 is kept constant; this would appear as increased overall T4)

Another way of thinking of this:

• Overall T4 = bound T4 + free T4

If we increase bound T4 and keep free T4 the same, we would still increase overall T4. Thus to know if she truly has hyperthyroidism we must look at free T4 concentration.

Atrial myxomas are the most common cardiac tumor in adults, and they may cause embolus complications hence our lady's painless loss of vision, likely due to central retinal artery occlusion [FA2020 p316]

The histology is characteristic of a myxoma with gelatinous material and cells immersed in glycosaminoglycans.

According to Daddy Goljan, basically for primary heart tumors if its an adult its a myxoma, if its a kid its a rhabdomyoma.

A couple ways to approach this question: (Vitamins found starting FA2020 p65)

• Pale, bulky stools with increased fat concentration - This is indicative of fat malabsorption. Even without identifying the child's disorder (likely cystic fibrosis because of this and the lung involvement) you can use this tid-bit of info to narrow the answers to the vitamins that are poorly absorbed in fat malabsorption (i.e. the fat-soluble vitamins ADEK). This would eliminate all but two answers, and being able to realize that vitamin D is associated with Rickets in children (bone issues, NOT neuro) while vitamin E is associated with neurologic issues (because of its antioxidant properties) would lead you to the answer.
• If you did not realize that they were trying to get at fat malabsorption, you can still narrow down the answers if you know the other deficiencies. As mentioned above, vitamin D is rickets/bones so it can be eliminated. Vitamin C deficiency is scurvy which presents with swollen gums, easy bruising, weakened immune response, anemia, etc. none of which include neuro symptoms as described. Niacin (vitamin B3) deficiency leads to pellegra which is associated with the 4 D's - diarrhea, dermatitis, dementia, and death; and this boy does not have dermatologic symptoms and his neurologic symotoms are not characteristic. Biotin (vitamin B7) deficiency is rare and associated with dermatitis, enteritis, and alopecia. Vitamin E associated with ataxia and demyelination of the posterior columns leading to decreased position and vibration sense, so it matches the symptoms.\

This man likely has an indirect inguinal hernia (because they are more common in men and overall, and weightlifting puts you at risk for development) [FA2020 p370)

A possible complication of hernias is strangulation of bowel that gets trapped.

This is one of the main consequences of liver failure. [FA2020 p389]

The proposed mechanism is an imbalance in free testosterone and estrogen caused by defect in sex hormone binding globulin (more free estrogen = gynecomastia).

Fibromuscular dysplasia is a common cause of renal artery stenosis in young/middle aged females (FA2020 p 604)

Fibromuscular dysplasia is associated with the characteristic beads on a string appearance on angiogram (p300).

Hyaline arteriolosclerosis is thickening of vessel walls secondary to plasma protein leak, commonly found in essential hypertension or diabetes (p301).

This man has Kartagener syndrome, which has immotile cilia due to a dynein arm defect (FA2020 p49)

Important question parts that point to Kartagener syndrome:

• Recurrent sinusitus and bronchitis - lack of motile respiratory cilia predisposes these individuals to upper respiratory tract infections
• Potential infertility - he is 35 and he is married with no children (though it never mentioned he had tried for children), individuals with this defect have immotile sperm and thus reduced fertility
• *Point of maximal impulse at the 4th intercostal space on the right - This is indicative of *situs invertus which is heavily associated with Kartagener syndrome. This is probably the "buzz" for the question that should point you to the diagnosis and therefore answer
• The nasal polyps with squamous metaplasia are also associated with Kartagener syndrome

DISTRIBUTIVE SHOCK (I.E. SEPTIC OR ANAPHYLAXIS) ARE THE ONLY SHOCKS WITH INCREASED CARDIAC OUTPUT!

FA2020 p310

This man presents with hypothermia (septic shock can present with hyper or hypothermia), tachycardia, and low blood pressure with increased cardiac output, characteristic of septic shock. Further distributive shock is associated with severe decrease in systemic vascular resistance while other forms of shock have increased systemic vascular resistance.

This woman has gout which is associated with hypertension and diabetes and attacks can be precipitated by diuresis (such as with furosemide). Negatively biorefringent crystals (uric acid crystals) are also characteristic of gout. Gout is associated with kidney stones (nephrolithiasis). [FA2020 p467]

This individual has ankylosing spondylitis (FA2020 p469)

Ankylosing spondylitis is a seronegative spondyloarthritis (meaning not associated with rheumatoid factor) more common in men which has symmetric involvement of the spine and sacroiliac joints. Symptoms include inflammatory lower back pain which improves with exercise and is worsened by immobility. X-rays of the sacroiliac joint would help confirm the diagnosis by showing ankylosis (joint fusion) characteristic of this disorder.

Just to add to the explanation here is what you would see in the others (most on FA2020 p484)

• Basal cell carcinoma:
• "Palisading" nuclei as well as nests of neoplastic basal cells.
• Typically presents as a pearly, indurated nodule but can be a scaling plaque


• Keratoacanthoma:
• Resembles squamous cell carcinoma in that it is a rapidly growing dome shaped nodule with a keratin filled center
• On histology it basically presents as a crater filled with keratin


• Malignant melanoma:
• Bad boi, look for the ABCDEs (asymmetry, border irregularity, color variation, diameter >6mm, and evolution)
• On histology you see melanocyte proliferation below the basement membrane and it just looks uglier


• Merkel cell carcinoma:
• Rare and typically appears as flesh colored or bluish nodule

IgG can be aquired from the mother by crossing the placenta, but IgM cannot. Thus, the presence of IgM indicates that the baby has encountered the infection in utero and generated its own antibodies to the infection. So the baby has congenital CMV. (See FA2020 p105 for information on immunoglobulin isotypes)

NOTE: IgM is the first antibody formed in response to infection and for most serologies IgM presence will be indicative of ongoing infection.

Epstein-Barr virus is associated with lymphomas (endemic Burkitt Lymphoma, Hodgkin lymphoma, CNS B-cell lymphoma), nasopharyngeal carcinoma, and lymphoproliferative disease in transplant patients. (FA2020 p164)

Here is a chart of virus-associated cancers and their viruses. Also found FA2020 p226.

• CMV is not associated with cancer but is associated with AIDS retinitis and esophagitis.
• Hepatitis B is associated with hepatocellular carcinoma.
• HHV-8 is associated with Kaposi sarcoma in AIDS patients (an endothelial neoplasm, FA2020 p478)
• HTLV-1 (human T-CELL...) is associated with adult T-cell leukemia

Below are links to pictures of what each organism would look like on a stain:

• Babesiosis is fever and hemolytic disease predominantly in the northeast US, usually presents with classic "maltese cross" in RBCs [FA2020 p157]
• Leishmaniasis can be cutaneous with ulcer presentation or visceral with spiking fevers, hepatosplenomegaly, and pancytopenia. The amastigotes are present in macrophages not RBCs [FA2020 p158]
• Malaria is caused by the plasmodium species and presents with trophozoite ring forms in RBCs. It is transmitted by the anopheles mosquito and is endemic in parts of Africa. It causes fever, headache, anemia, and splenomegaly [FA2020 p157]
• Toxoplasmosis is is an intracellular parasite but a small numbr exist extracellularly as tachyzoites in blood; it can also cause tissue cysts filled with bradyzoites. In immunocompetent hosts it produces mono-like symptoms but in immunocompromised it will dissiminate and cause ring-enhancing brain/tissue abscesses. [FA2020 p156]
• Trypanosomiasis can be caused by Trypanosoma bruceii (African sleeping sickness, p156) or Trypanosoma cruzii (Chaga's disease, South America, p158). These organisms are extracellular on blood smear.

A few of the hints that point to rheumatoid arthritis over the other answers:

• Younger age of onset and female - rheumatoid arthritis is an autoimmune disease and can thus present in younger females whereas osteoarthritis is from wear and tear so it is usually older individuals (FA2020 p466 for osteoarthritis vs rheumatoid)
• Sparing of the distal interphylangeal joints (DIP are spared in rheumatoid arthritis) and bilateral - in the other disorders there is not necessarily selectivity for the PIP and MCP, and they would not necessarily be bilateral (i.e. gout is not necessarily bilateral) wheras rheumatoid arthritis is bilateral
• Pannus formation - the formation of nodular pannuses is characteristic of rheumatoid arthritis over other disorders (especially once gout is eliminated the presence of nodules points most to rheumatoid arthritis)
• SLE would be likely be associated with other associated symptoms (p470)
• Also the arthritis in lupus is nonselective for joint type
• Scleroderma does not commonly present with arthritis or joint pain (p473)

He has Huntington's disease (hence the irritability, depression, and chorea - sudden, jerky, purposeless movements) (FA2020 p520)

Huntington's is autosomal dominant so family history would be apparent.

Wegener granulomatosis, also called granulomatosis with polyangiitis, is a vasculitide that commonly presents with the triad of focal necrotizing vasculitis, necrotizing granulomas in the lung and upper airway, and necrotizing crescentic glomerulonephritis (FA2020 p 314 and 596)

Wegener is associated with chronic sinusitis, hemoptysis, and PR3-ANCA (antineutrophil cytoplasmic antibody, formerly called c-ANCA).

None of the other answers are associated with ANCA except Churg-strauss syndrome. Churg-strauss syndrome (also called eosinophilic guanulomatosis with polyangiitis) is associated with MPO-ANCA (formerly called p-ANCA). However, Churg-strauss does not have lower respiratory involvement, hemoptysis, or patchy lung opacities on CXR.

Ringing in his ears (tinnitus) combined with mixed metabolic acidosis-respiratory alkalosis is hallmark of aspirin overdose (salicylate poisoning) [FA2020 p486]

• He is in metabolic acidosis (his HCO3- is also low)
• He is in respiratory alkalosis (his PaCO2 is low)

You might be thinking - is the PCO2 low because compensation?

Use Winter's formula: PCO2 = 1.5(HCO3-) + 8 (+ or - 2)

1.5(19)+8 = 36.5 so he should have a PCO2 34.5 to 38.5

His PCO2 is 30 so he has cocominant respiratory alkalosis.

[Acid base and Winter's equation FA2020 p592]

Tracheoesophageal atresia is associated with increased amniotic (polyhydramnios) fluid due to the inability of the fetus to swallow the amniotic fluid (FA2020 p641 and 359).

• Cleft lip is not associated with swallowing abnormality and therefore not associated with polyhydramnios.
• Encephalocele is a neural tube defect where the brain protrudes through the skull and into a sac-like covering. It is not associated with polyhydramnios (anencephaly which is a completely open skull with no forebrain is associated with polyhydramnios due to lack of swallowing center in the brain)
• Renal agenesis would be associated with OLIGOhydramnios (too little amniotic fluid) because the baby cannot produce urine. This leads to Potter's sequence (FA2020 p578)
• Urethral obstruction would also lead to oligohydramnios due to decreased urine production.

The question is essentially asking which of the following would be associated with Bulemia with purging (the woman's condition). The best answer is parotid gland enlargement (FA2020 p567)

Lichen sclerosus is a vulvular pathology involving thinning of the epidermis with fibrosis/sclerosing dermis, most commonly presenting with skin fragility (paper-thin) in post-menopausal women (FA2020 p644)

The other answers do not fit:

• Candidal infection = itchyness and cottage cheese discharge; the excessive itching can lead to lichen sclerosus but would also be treated by the miconazole
• HPV = genital warts or cervical cancer
• Trichomoniasis = itchy with green smelly discharge, see organisms on microscopy
• Urethral prolapse = rare, painful, would not cause these symptoms and would cause swelling in urethral area

Total gastrectomy = absence of parietal cells

Parietal cells are necessary to secrete intrinsic factor which binds vitamin B12 to allow absorption.

Also his symptoms (which fit the description of subacute combined degeneration) are characteristic of B12 deficiency.

FA2020 p69 (insert sunglasses emoji here)

Uterine conditions FA2020 p648

• Adenomyosis - extension of uterine endometrial glandular tissue into the uterine myometrium; would present with dysmenorrhea or abnormal uterine bleeding with a uniformly enlarged soft and globular uterus
• Endometrial hyperplasia - abnormal endometrial gland proliferation, abundant tissue but no dysplasia; presents with heavy bleeding during menses, more common in nulligravid due to excess estrogen
• Endometrial metaplasia - metaplasia is transformation of one cell type to another; this can be a benign process or associated with malignancy but would not likely present with abundant tissue on curretage
• Endometriosis - endometrium-like glands/stroma outside of the uterine cavity (in ovary, pelvis, or peritoneum); presents with PAIN and heavy bleeding or dysmenohorrea
• Endometritis - inflammation of the endometrium, associated with retained products of conception or foreign body

Osteomyelitis is a common complication of sickle cell disease and can be distinguished here because of the elevated WBC/neutrophil (indicating bacterial infection). It is important to note the most common cause of sickle cell osteomyelitis is Salmonella or Staph aureus (in a healthy individual the most common cause is Staph aureus). [FA2020 p180 and 422]

I don't like how they are asking this, but I think what they are getting at is that after the stent placement ("subsequent to the stent placement") there will be reperfusion injury to the myocardial tissue which occurs through free radical injury and therefore membrane lipid peroxidation is the best answer (FA2020 p210 mentions membrane lipid peroxidation as a mechansism of free radical damage and lists reperfusion injury after thrombolytic therapy as a type). Elevations in the cardiac enzymes I assume are because of the injury to the cells.

Cyclophosphamide is an alkylating agent which cross-links DNA at guanine and interferes with DNA replication (FA2020p441)

Other alkylating agents that interfere with DNA replication include busulfan, isofosfamide, nitrosureas and procarbazine (procarbazine is nonspecific).

Other answers:

• Imatinib/dasatinib/nilotinib targets the BCR-Abl tyrosine kinase and are used for CML (p443)
• Caspase 3 is not a direct target of any chemotherapeutic.
• DNA histone deacetylase is the target of HDAC inhibitors, not in First Aid but approved for some T-cell lymphoma.
• DNA polymerase alpha is one of the eukaryotic DNA polymerases. It is responsible for initiation and some synthesis of lagging strand but does not have the high processivity of Pol delta. It is not directly targeted in any therapy.
• DNA topoisomerase II inhibitors include etoposide, teniposide (primarily solid tumor use, p442), doxorubicin, danorubicin (solid tumors, leukemia, lymphoma, p439). DNA Top I inhibitors are also important antitumor agents, including irinotecan and topotecan (p442)
• Epidermal growth factor receptor tyrosine kinase (EGF tyrosine kinase) inhibitor is Erlotinib, and it is important in combatting non-small cell lung cancer (p442)

Caspofungin inhibits cell wall synthesis in fungi by inhibiting synthesis of beta-glucans (FA2020 p200).

Fat, fourties, female is at increased risk for gallstones because of her liver increasing cholesterol synthesis. (FA2020 p396)

He has an upper motor neuron lesion which is causing paralysis on his left lower side, so he will have hyperreflexia on this side. Thus the deep tendon reflex will actually be increased/strongest in his left achilles tendon initially after the accident. [FA2020 p529]

Warfarin inhibits epoxide reductase which interferes with synthesis of the vitamin K dependent clotting factors. Of the clotting factors, VII has the shortest half-life and thus will be first to be decreased to 50%.

NOTE: Protein C also has an extremely short half-life and its decrease before that of the clotting factors can cause an initial hypercoaguable state after warfarin is begun. This is why heparin therapy is used to "bridge" patients.

This individual has horizontal conjugate gaze palsy, likely intranuclear opthalmoplegia which is commonly a symptom of MS (hence her relapsing remitting history) [FA2020 p543]

Intranuclear opthalmoplegia can be caused by a lesion in the medial longitudinal fasciculus, which is located at "C" on the diagram. Here is a picture pointing out the MLF, which cooresponds to C on the diagram.

The Medial Longitudinal Fasciculus is what allows for cross-talk between CNVI and CNIII for conjugate gaze.

This is Dissiminated Intravascular Coagulation (FA2020 p428)

DIC is a consumption coagulopathy (clotting factors are activated EVERYWHERE so they quickly produce microthombi and are consumed, allowing for bleeding). Thus, the individuals present with a consumption of coagulation factors leading to increased bleeding time, increased PT/INR, increased PTT, low fibrinogen and other clotting factors as well as a consumption of platelets leading to thrombocytopenia. Because there is widespread clotting factor activation, they also have signs of widespread microthombi sich as schistocytes and increased fibrin degradation products.

Answering this question requires general knowledge of the catecholamine synthesis pathway (FA2020 p83).

The approach I took to this question was mainly elimination of wrong answers:

• MAO (monoamine oxidase) could be eliminated because she is lacking epinephrine and since MAO is involved in the breakdown of catecholamines, a deficiency in MAO would increase concentrations of norepinephrine and other catecholamines.
• Norepinephrine transporter could be eliminated because inhibition of reuptake of norepinephrine would, again, increase norepinephrine concentrations and she has decreased concentration.
• Tyrosine hydroxylase can be eliminated because it is the first step in catecholamine synthesis and required for dopamine synthesis, and as she has increased dopamine this step is not deficient.
• Amino acid decarboxylase, or L-amino acid decarboxylase also called DOPA decarboxylase, is also required in dopamine synthesis and can be eliminated because of her increased dopamine concentration.

This leaves the answer, dopamine beta-hydroxylase.

Splenectomy is indicated for hereditary spherocytosis because it is an intrinsic hemolytic anemia where the spleen is destroying the red cells even though they could technically function fine. Thus splenectomy will prevent premature removal by the spleen (FA2020 p422).

Sickle cell disease causes autosplenectomy/splenic infarct/sequestration but splenectomy is not indicated because the spleen is not contributing to the symptoms of sickle cell, the symptoms are caused by the vasoocclusive disease.

Cyclosporine is an immunosuppressant that blocks T-cell activation by preventing IL-2 transcription (FA2020 p120)

Even without remembering the mechanism of cyclosporine, the answer could be inferred as most medications used after kidney transplant (cyclosporine, tacrolimus, sirolimus, basiliximab) block T-cell activation. This mechanism MAKES LOGICAL SENSE because T-cells are the primary mediators of acute rejection, which is what we are trying to prevent directly after a kidney transplant.

This is Neurofibromatosis Type I, which is an autosomal dominant disease (FA2020 p60, 525)

Even if you did not know this fact, you could likely guess autosomal dominant based on the inheritance pattern and general disease described. It is VERY COMMON in the family on one side (the mothers) and it did not skip a generation. Autosomal recessive skips generations. Mitochondrial with variable penetrance could be possible, but the disease pattern for mitochondrial are myopathies, metabolic, or optic neuropathy. X-linked would have ALL of the sons of the mother affected (whether it was dominant or recessive).

This is Pemphigus Vulgaris (FA2020p480)

It can be distinguished because of the flaccid bullae (blisters), epidermal acantholysis (acantholysis means loss of intercellular connections resulting in loss of cohesion between keratinocytes), and intraepidermal blistering.

Pemphigus vulgaris is due to formation of autoantibodies against desmosomal proteins.

Not an answer choice but the reason they said "intact basal layer of keratinocytes adherent to the basement membrane" is to distinguish it from Bullous pemphigoid, which is where sutoantibodies against HEMIdesmosomes cause the keratinocyte layer to peel away from the basement membrane. The blisters are often tense in bullous pemphigoid as well.

Monoclonal antibodies used for inflammatory bowel disease include infliximab and adalimumab, both of which are directed against TNFalpha (FA2020 p382, 122, 487)

Another way of thinking about this is to think about common therapeutic antibodies used as well as the function of the other things listed to eliminate them. TNFalpha is commonly blocked by biologics for therapy in autoimmune and inflammatory disease, and generally it makes sense it would be beneficial to block as it is one of the primary pro-inflammatory cytokines

Bradykinin is involved in inflammation but has no major therapeutic Abs targeting it. C5a is an anaphylotoxin, and though monoclonal antibodies targeting C5 do exist they are used to treat paroxysmal noturnal hemoglobinuria. C5a does not play a major role in the pathogenesis of IBD. Blocking class I MHC antigens does not make sense, as antigens are what elicit the immune response and are presented to T-cells and there are millions of possible antigens that could be presented that are eliciting the inflammatory response. If you block class I MHC ittself it would also be extremely detrimental as then CD8 T-cells would not be able to respond to any infection/etc. Fibrin is involved in the clotting pathway and would not be beneficial to block in IBD. PGE2 is associated with pain, but it is not targeted by any therapeutic antibodies.

Aflatoxin is from Aspergillus and is associated with contact with stored grains or nuts (hence peanut farmer. Aflatoxin increases risk of hepatocellular carcinoma [FA2020 p225 and 392]

One hard part of this question (aside from remembering the semi-random carcinogen) is knowing that this is hepatocellular carcinoma even though they try to throw you off with a positive Anti-HepA IgG. Anti-HepA IgG can be found from prior infection or from vaccination and actually protects against reinfection (FA2020 p174), and based on his other negative serology he is unlikely to have a hepatitis virus currently active. Further, the finding of a single lesion with the histology that includes dysplasia and no normal architecture screams cancer.

Nitrosamines are associated with gastric carcinoma. Nicotine on its own is not associated with cancer but smoking is associated with loads of squamous cancer and transitional cell carcinoma of the bladder, among others. Mercury is not specifically associated with any cancer but can cause toxicity.

This man has malignant hyperthermia, a rare but life-threatening complication of some anesthetics (particularly the volatile/inhaled) (FA2020 p550)

The treatment is dantrolene, a ryanodine receptor antagonist which decreases calcium release from the sarcoplasmic reticulum (Dantrolene is also used as a treatment for neuroleptic malignant syndrome).

If you want a refresher on what the heck a ryanodine receptor (RYR) is: (FA2020 p456)

• In skeletal muscle, the RYR is the calcium channel on the sarcoplasmic reticulum which is coupled to a voltage sensitive dihydropyridine calcium channel.
• Remember skeletal muscle is calcium channel induced calcium release, so it is an actual physical coupling of the receptors which causes the RYR to open (this is different than in cardiac muscle where the RYR are calcium induced, and it is a binding of calcium that triggers their opening)
• In the heart, dihydropyridine receptors are also called L-type calcium channels or Long-acting. T-type are a completely different channel and are transient (respond to lower voltage). RYR are still RYR but a different subtype than in skeletal muscle.

T10 is the dermatome level for the umbilicus, hence the periumbilical discomfort (Landmark dermatomes FA2020 p510)

In appendicitis, the first pain is generalized referred pain and comes from stimulation of visceral afferents (which is why it is poorly localized). Pain eventually localizes as irritation to the parietal peritoneum occurs (FA2020 p383)

This protein is an uncoupling agent (likely thermogenin which is found in brown adipose and serves to increase heat production. Uncoupling agents will cause increased permeability of the mitochondria membrane, necessitating more oxygen consumption in order to generate the same ion gradient. Since more oxygen is consumed to generate the same gradient, more oxygen would be consumed to generate the same amount of ATP, so the ratio of oxygen consumption to ATP generation increases. (FA2020 p78)

Another way of thinking about this is that oxygen will continued to be consumed to attempt to generate the gradient, but the leaky membrane will prevent the gradient from being formed properly and therefore prevent ATP from being formed. Thus there is the same amount of oxygen consumed for little to no ATP being made so again the ratio of oxygen consumption to ATP generation increases. This is closer to what actually happens in the body but I found it easier to think about it the first way.

This boy likely has ADHD (disruption and inability to concentrate in more than two settings [school and home]). First-line treatment for ADHD in children are stimulants such as methylphenidate/ amphetamines, which work by increasing release of dopamine and norepinephrine. (FA2020 p572)

Preferred medications for select psychiatric treatments also p572

The most commonly used medications for erectile dysfunction are the phosphodiesterase inhibitors (specifically PDE5 inhibitors which include Sildenafil/Viagra). (FA2020p246)

PDE5 inhibitors (-afils) work by inhibiting the hydrolysis of cGMP by phosphidiesterase, increasing cGMP levels in smooth muscle cells causing relaxation/dilation and allowing the corpora cavernosa to fill with blood (viola, erection).

This individual is suffering from hypocalcemia, which explains the seizures, twitching (reason for Chvostek sign - tapping of the facial nerve causing contraction of the muscles), and spasms (similar to Trousseau sign - inflation of the blood pressure cuff causing carpal spasm). It also may present with QT prolongation and numbness and tingling (as described). It is also important to note that though mild hypocalcemia causes hyporeflexia, extreme hypocalcemia can lead to hyperreflexia, tetany, parasthesias, and seizures (see here). Basically you cannot bank on the reflexes.

Hypercalcemia would present with stones (renal), bones(pain), groans(abdominal pain), thrones( urinary frequency), psychiatric overtones(anxiety, altered mental status).

The others answers are incorrect because:

• Bicarbonate disturbances are related to acid/base imbalance and would not present with the symptoms described.
• Chloride:
• Hypochloremia (associated with excessive vomiting) is typically accompanied by hyponatremia and typically presents with weakness/fatigue and dehydration.
• Hyperchloremia disturbances are generally related to kidney issues and when signs present they are dehydration, excessive thirst, fatigue, and dry mucus membranes
• Potassium:
• Hypokalemia presents with muscle cramps, spasm, and weakness but also with cardiac anomalies (arrhythmias) and flattened T-waves on ECG.
• Hyperkalemia presents with wide QRS and peaked T waves on ECG, weakness, and arrhythmias.
• Sodium:
• Hyponatremia can cause seizures and stupor, but it also typically presents with nausea and vomiting, weakness/fatigue, and confusion. Here is a good hyponatremia pneumonic (SALTLOSS - Stupor, Anorexia[nausea, vomiting], Lethargy, Tendon reflexes decreased, Limp muscles/weakness, Orthostatic hypotension, Seizures, Headache)
• Hypernatremia presents with irritability and stupor

Electrolyte Disturbances: FA2020 p591

This is normal menopause (FA2020 p636). Average age of onset is 51 years (our woman is 52). Hot flashes are a common symptom.

In menopause, the ovaries stop secreting estrogen (17beta-estradiol is an estrogen) due to a decline in the number of ovarian follicles with age. FSH is increased because the feedback inhibition is removed. The source of estrogen after menopause becomes peripheral conversion of androgens.

The key here is "wound healing". TGF-beta is a vital cytokine in the healing process as well as in attenuation of immune response (FA2020 p216)

FGF, TGF-beta, VEGF, PDGF, EGF (all GROWTH factors ending in GF which promote healing) as well as metalloproteinases (for remodeling) are vital in the wound healing process.

TGF-beta and IL-10 are the two "resolution" cytokines vital in attenuating the immune response. FA2020 p108 has important cytokines.

The kidney secretes prostaglandins in a paracrine fashion, and prostaglandins dilate the afferent arteriole to increase renal blood flow (FA2020 p589).

Here is a diagram.

This is an epidural hemorrhage, as noted by the biconvex shaped hematoma on CT. Epidural hemorrhages are due to rupture of the middle meningeal arteries (FA2020 p513) Epidural hematomas commonly have loss of consciousness, then a lucid interval before quick decline to coma.

Shearing of the bridging veins occurs in subdural bleeds. Subdural hematomas present as a "crescent moon" shape on CT. Seen in shaken baby syndrome.

Subarachnoid hemorrhage is usually caused by rupture of a saccular aneurysm or AV malformation and leads to the "worst headache of my life" and blood molding to the cerebral sulci. The sigmoid and transverse sinuses are dural venous sinuses. Dural venous sinus thrombosis with secondary venous hypertension can cause subarachnoid bleed but is rare.

Bleeding from the lenticulostriate arteries presents as an intraparenchymal hemorrhage within the basal ganglia ans is commonly due to hypertension. These would present as hypodense areas within the brain tissue rather than on the exterior.

This woman is showing signs of HELLP syndrome (Hemolysis, elevated liver enzymes, low platelets) [FA2020 p643] HELLP can lead to DIC.

A blood smear will show schistocytes.

HELLP syndrome is a manifestation of severe preeclamspia (hypertension after 20 weeks with either proteinuria or end-organ dysfunction).

This child likely has a meningomyelocele (neural tube defect caused by failure of the neuropores to fuse in week 4, FA2020 p491). Neural tube development in general occurs weeks 3-8 (FA2020 p612) which corresponds most closely to days 15-40. Organogenesis and most vital development also occurs during this period.

Days 1-10 are typically "all or nothing" in that a defect would cause fetal demise.

Days 60-75 (~weeks 8-10) are associated with external genital development, palate and teeth.

The most critical periods are typically over by week 10 (see this chart)

In androgen insensitivity syndrome, the testes may descend and push through into the labia majora. Thus the labia majora corresponds to the scrotum. (FA2020 p639)

Here is a diagram of corresponding embryological structures. FA2020 p622 discusses sexual differentiation but doesn't go as in depth with which exact structures correspond.

He has Vibrio cholera, as indicated by the gram-negative comma shaped organism and "rice water" stool and travel history. Cholera toxin causes constitutive activation of adenylyl cyclase leading to increased cAMP, increased chloride secretion and extreme watery diarrhea (FA2020 p146)

(Organisms with exotoxins FA2020 p132)

She has a craniopharyngioma, the most common childhood supratentorial tumor which is derived from remnants of Rathke's pouch (FA2020 p528). Craniopharyngiomas commonly have calcification and can cause hypopituitary issues (like low HGH). Suprasellar is also the location of the pituitary, and pituitary tumors in general cause bitemporal hemianopsia due to compression of the optic chiasm.

Rathke's pouch (where craniopharyngiomas and anterior pituitary are derived from) is derived from the surface ectoderm of the oral cavity.

Note that the neurohypophysis (posterior pituitary) is derived from neural ectoderm while the adenohypophysis (anterior pituitary) is derived from surface ectoderm of the oral cavity.

His low urine specific gravity combined with excessive thirst and urination indicates diabetes insipidus, which can be central (defect in the posterior pituitary production of ADH) or nephrogenic (kidney nonresponsive to ADH). (FA2020 p338)

Seeing as it asks us to ID the endocrine organ (and he does not have history indicative of nephrogenic, the less common variety), this indicates central diabetes insipidus and defect in posterior pituitary ADH production.

The 3 D's of Pellagra: Diarrhea, dermatits, dementa (and death)

He presents with the classic triad of symptoms for pellagra, vitamin B3/niacin deficiency. (FA2020 p67)

• This is not beriberi (B1/thiamine deficiency) - Beriberi may present with polyneuropathy and muscle wasting but not skin findings or diarrhea. Wet beriberi may also present with heart failure/cardiomyopathy. (FA2020 p66)
• Scurvy (C/ascorbic acid deficiency) presents with swollen gums, easy bruising, petichiae, corkscrew hairs, and weakened immune response (FA2020 p69)
• Wernicke syndrome (B1/thiamine) presents with confusion, ophthalmoplegia, and ataxia and is associated with chronic alcoholism. May progress to Korsakoff syndrome which is severe amnesitic disorder, confabulation, and personality change (p66)
• Whipple disease is caused by the bacteria Trophyrema whippili and is characterized by foamy PAS+ macrophages in the intestinal lamina propria, malabsorption, cardiac symptoms, arthralgias, and neuro symptoms are common (p381)

This can be identified as a splice site mutation because:

• It is not within the exon (coding region) so it cannot be a missense or nonsense mutation
• Missense is the coding of the wrong amino acid
• Nonsense is the premature insertion of a stop codon
• It is occurring in the intron, and since the majority of splice sites are GT-AG, this causes an alternative splice site (see here)
• Mutations are by definition an error that has been permanently incorporated into the DNA and thus the progeny of the cell so they are unlikely to interfere with replication (though mutations in the promotor region might interfere with transcription)
• Polyadenylation occurs after translation and mutations (unless they are in the proteins responsible for polyadenylation) are unlikely to interfere with polyadenylation. PolyA polymerase does not require a transcript

Eukaryotic mRNA processing = FA2020 p41

Even without knowing the splice site mutation code, the answer can be inferred from elimination.

This is likely poison ivy, which is a Type IV (delayed) hypersensitivity mediated by T-cells. [FA2020 p112]

Notes to point to poison ivy: itchy linear vesicles (as the leaf touched), camping trip, on the extremities which would likely be exposed

Delayed type hypersensitivity helpful hint: the rash did not appear until a few days after he had returned from camping (5 days ago camping, 2 day history of rash)

He has Clostridium difficile infection secondary to his course of amoxicillin. C. diff causes pseudomembranous colitis via toxins A (enterotoxin) and B (cytotoxin) [FA2020 p138].

Looking at the symptoms, they fit with cerebellar issue, as the cerebellum is responsible for modulating movement and aiding in coordination and balance. [FA2020 p499]

She does not have paralysis or parasthesia but rather lack of control of movement, making injury to the cerebrum less likely. Further, her issues are not localized to the upper or lower extremity and do not fit with any syndrome of spinal cord. Ataxia is also typically a buzzword for associations with the cerebellum. In this case, her limb ataxia is likely from a metastasis to the left cerebellar hemisphere.

If you want to review:

Common brain lesions can be found FA2020 p511.

Spinal lesions can be found FA2020 p530.

The basics of this question are what are the major chemotactic factors that attract neutrophils to the site of injury.

These are: IL-8, C5a, LTB4, kallikrein, and platelet activating factor

FA2020 p406 and 215

Important cytokines are on p108

The two most common defects in fatty acid metabolism are systemic primary carnitine deficiency and medium-chain acyl-CoA dehydrogenase deficiency or MCAD [FA2020 p89]. Both can present with physically normally appearing babies as the primary issues occur later (MCAD between 3 and 24 months and some variations of carnitine deficiency don't present until adolescence). Often the main danger is "hidden" in neonates unless prolonged fasting occurs because the individuals will go into hypoketotic hypoglycemic and can die. Thus, they are put on the newborn screens along with other disorders of fatty acid metabolism.

Thus, this neonate would have likely normal appearing physical exam and general labs. The best test of the list would be to look at acylcarnitine concentrations, which can be used to detect many disorders of fatty acid metabolism and some organic acidemias (https://neurology.testcatalog.org/show/ACRN)

Amino acids are not associated with fatty acid metabolism. ABG and electrolytes would likely be normal and would not be helpful in diagnosis. Lactic acid levels would be useful in neonates to give an idea of oxygen delivery to tissues, but is not useful here.

This is a choriocarcinoma, or a rare malignant trophoblastic tumor developed during/after pregnancy [FA2020 p642]. It is characterized by increased serum beta hCG and "cannonball" metastases to the lung. Biopsy would show trophoblastic tissue with no chorionic villi present.

Dermatomes! (YAY!) Also see FA2020 p452 for lower extremity nerves.

T10 dermatome is the level of the umbilicus.

L1/L2 would be upper medial and anterior thigh, not down to the foot. The most common buzzwords for injury (less likely via the mechanism in this question) would be absent cremasteric reflex as this is where the genitofemoral nerve originates. The cremasteric nerve is usually injured in laproscopic surgery.

L3/4 is correct because this cooresponds to the correct dermatome for the shooting pain.

S1/2 is associated with sciatica (sciatic nerve is L4-S3), which would be a shooting pain beginning in the buttocks and shooting down to the heel (see dermatomes). This is not described here. Also this is less likely because the sacral spinal cord is fused and less likely to get bony outgrowths. The most common cause of sciatica is an L5 bulging disc causing S1 compression.

S4/5 injury is associated with perianal numbness and potential fecal incontenence(pudendal nerve is S2-S4). However this injury would not be atypical because the sacral spinal cord is fused and less likely to have bony outgrowths causing compression.

She has Mycoplasma pneumoniae which causes walking (atypical, interstitial) pneumonia and increase in cold agglutinins (IgM)

FA2020 p150

If you are a sketchy person (which I am not), I am pretty sure Mycoplasma is depicted in the cold, or as a guy on skis in drug ones, which can help you remember cold agglutinins. Also Mycoplasma -> IgM (the letter M).

Also (for immuno nerds or rationalizers), IgM is the first antibody to be produced so it would make sense that you would have IgM this early in the infection which can cause cold agglutination (she has only been sick for a few days). IgG causes warm agglutination, which is typically seen in more chronic processes like SLE and CLL (FA2020 p423). No idea if that is the actual mechanism but it is how I keep them straight in my mind and makes sense.

FA2020 p116

Leukocyte adhesion deficiency presents with late separation of the umbilical cord, absence of pus (since pus is made of neutrophils), and dysfunctional neutrophils leading to recurrent skin and mucosal infection

LAD is due to a defect in LFA-1 integrin on phagocytes causing deficiency in adhesion and transmigration.

She has Heparin induced thrombocytopenia, which can be deduced due to the decrease in platelet count after medication administration and the fact that she was being treated for a massive PE. Heparin is used for immediate anticoagulation of PE and to treat DVT recurrence (FA2020 p436).

Symptomatic HIT (Type 2) is caused by development of IgG antibodies against platelet bound factor 4.

The mechanism of heparin is potentiation of the action of antithrombin, which decreases the action of thrombin and factor Xa and therefore acts as an anticoagulant

First step to approach this problem is to eliminate Listeria monocytogenes (it is a gram positive ROD) and both staphylococcal species (Staph is always catalase positive), which leaves us with Streptococcus pneumoniae and Enterococcus faecalis.

Strep pneumoniae is an alpha hemolytic strep while enterococcus is typically gamma hemolytic, so seeing as there is no hemolysis on blood agar (meaning gamma hemolytic), Enterococcus is the correct answer. VRE (vancomycin resistant enterococcus) are also an important cause of nosocomial infections such as from his venous catheter.

Here is a good algorithm/flow chart for gram positive identification!

The Congo Red staining showing characteristic birefringence (usually described as apple green) is indicative of amyloid (FA2020 p212). Her findings are characteristic of secondary amyloidosis with serum amyloid A which can cause restrictive cardiomyopathy and nephrotic syndrome and is associated with rheumatoid arthritis.

Amyloid protein composition is misfolded aggregates of beta-pleated sheets.

This is basically a question of terminology. (FA2020 p219)

Invasive means it has penetrated the basement membrane but "microinvasive" would assume it has not invaded surrounding tissues as it has not metastasized.

A primary means of protein degradation within the cell is ubiquitination of proteins which targets them for degradation by the proteosome. (see image)

E6 hijacks this system and causes ubiquitination of p53 (see image)

Basically if there is a question about degradation of a protein in the cell its likely through ubiquitination.

Pelvic splanchnic nerves carry the parasympathetic fibers that are responsible for hindgut intestinal motility including voiding (image). [FA2020 p364].

Diabetes mellitus can cause nerve damage and gastroparesis, treated with metoclopromide (FA2020 p400).

These individuals have a poluymorphism in the breakdown pathway of 6-MP. Like most polymorphisms in drug breakdown pathways, this will lead to buildup of toxic metabolites unless the drug dose is decreased (i.e. the 6-MP will be shunted into the pathway that makes the toxic 6-thioguanine).

6-MP and its prodrug azothioprine inhibit purine synthesis (FA2020 p36 and p440).

This mainly has to do with the location of the SA node (see here). The SA node is located in the atrial wall at the junction of the superior vena cava and right atrium.

The AV node lies near the back of the intraventricular septum near the opening of the coronary sinus (the triangle of Koch defines the AV node location)

Other fun facts from UWorld about ablation and different sites of origin, etc:

• Between the tricuspid and inferior vena cava (cavotricuspid isthmus) is the most likely location of a reentrant circuit causing atrial flutter
• The pulmonary vein ostia is the most likely site of origin for AFib and therefore most likely targeted for catheter ablation to correct Afib
• The right ventricular outflow tract and papillary muscles are the most likely site of origin for Idiopathic VTach (though it is more commonly from ischemic tissue)
• An accessory pathway bypassing the AV node is the cause of Wolff-Parkinson-White syndrome (characteristic delta wave upstroke) and AV reentrant tachycardia
• A slow pathway that reenters the AV node is the cause of AV nodal reentrant tachycardia and the slow pathway would be targeted for ablation

Alendronate is a bisphosphonate which acts as a pyrophosphate analog and binds hydroxyapatite in bones and inhibits osteoclast activity. (FA2020 p486)

As a general rule, most drugs of osteoporosis inhibit osteoclast activity and bone resorption somehow (the bisphosphonates, calcitonin mimetics [directly bind a receptor on osteoclasts], estrogens/SERMs [inhibit PTH mediated bone resorption and cytokine secretion], Denosumab [mAb which inhibits RANKL which typically activates osteoclasts]). The ONLY FDA approved medication which has the ability to stimulate bone formation is teriparatide.

(FA2020 p462 osteoporosis)

Maxillary nerve injury (specifically the infraorbital nerve) is an important potential complication of orbital rim fractures (e.g. blow out fractures) [See here]

Here is a picture of the territories of the different branches of the trigeminal nerve for sensation which could help you answer this question as he has numbness under the eye to the upper lip.

Orbital floor fractures can lead to entrapment of the inferior rectus, which can be a cause of pain on upward gaze and diplopia when asked to look upward. This is an ophthalmologic emergency (https://emedicine.medscape.com/article/825772-overview).

Hormone sensitive lipase (HSL) is the enzyme which degrades triglycerides stored within adipocytes (FA2020 p93). Thus, it makes sense that it is activated in times of fasting and suppressed in the fed state.

Insulin would inhibit HSL, as insulin is a fed state enzyme secreted by the pancreas and would want to trigger storage of triglycerides.

In contrast glucagon is secreted in response to hypoglycemia by the pancreas and will trigger fasted state activation. In terms of the fed/fast state I always think of glucagon and epinephrine kind of like a superhero and their side kick, because they usually work together in the fasting state on similar targets to ensure the body has enough energy (this helps me remember that epinephrine and glucagon are fasting state hormones). Here though is epinephrine's big action away from glucagon, where glucagon has minimal effect and epinephrine has the big action of activating HSL! Glucagon has a minor role and other catecholamines and ACTH can also serve to activate HSL as well.

Another example of the synergistic work of glucagon and epinephrine is in glycogen breakdown (FA2020 p85). Both will trigger cAMP increase and protein kinase A activation which will phosphorylate glycogen phosphporylase and activate it (FAST PHOSPHORYLATE! Hormone sensitive lipase is actually phsophorylated to activate it as well).

FUN FACT: Hormone sensitive lipase actually got its name because it was sensitive to epinephrine!

This is a Congenital Diaphragmatic Hernia (FA2020p370).

Conginital diaphragmatic hernias are caused by a congenital defect of the pleuroperitoneal membrane which allows contents of the abdominal cavity to herniate upward, and displace the contents of the thorax (hence why our baby has displacement of the mediastinal contents to the right). This also leads to lung malformation and respiratory distress (hence the low apgar scores). Because the stomach is likely herniates upward, a nasogastric tube placed would appear in the left mediastinum (because that is where the stomach is). Further, there is an absence of bowel gas in the abdomen likely because the bowels are herniated into the thorax.

Here is a great image showing the timeline for the different pubertal changes in males and females. Tanner stages are found in FA2020 p673.

In females, the earliest detectable sign of pubertal change is breast bud development which only slightly precedes pubic hair development. In males, testicular enlargement is the first detectable sign.

The patient's history of 2 years decreased force of urinary stream and increased need to urinate throughout the night combined with his age is suggestive of benign prostatic hypertrophy causing obstriction of the urethra. He subsequently developed renal failure characterized by bilateral hydronephrosis and dilated ureters, suggesting "backup" of urine likely due to obstruction from prostatic hypertrophy. This "backup" puts back pressure into the kidney tubules and ultimately bowman's space, and thus causes increased hydrostatic pressure in Bowman's space leading to decreased GFR and renal failure.

This question is essentially asking what happens to sympathetic and parasympathetic efferents in the setting of hypovolemia/dehydration. In this setting, there would be lower blood pressure and thus this would cause reduced firing of the carotid baroreceptors, ultimately leading to feedback which stimulates the sympathetic nervous system (to increase heart rate and cause peripheral vasoconstriction in order to compensate for hypovolemia) while also inhibiting the parasympathetics.

L uteinizing hormone stimulates L eydig cells to make testosterone. (FA2020 p628)

Primary gonadal dysfunction (general hypogonadism)would result in low testosterone but high luteinizing hormone because less testosterone is available to cause feedback inhibition in the pituitary. This also makes sense because if the cells are not making enough testosterone but the pituitary thinks they should be, it will keep trying to tell them to make testosterone by secreting more and more luteinizing hormone (LH).

Central dysfunction (dysfunction at the level of the pituitary/hypothalmus or hypogonadotropic hypogonadism) would have low LH because either LH cannot be secreted or there is an issue with understanding the feedback of low testosterone.

Thus measuring LH will let us know where our patient's dysfunction lies.

Sleeps better sitting upright - left heart failure symptoms

JVD and anke edema - right heart failure symptoms

Right heart failure with backup into the venous system causes edema by increasing capillary hydrostatic pressure (the push pressure) and "pushing" more fluid into the interstitial tissue space.

Decreased plasma colloid oncotic pressure (the pull pressure) could technically also cause edema but this would be likely more associated with a history of symptoms of loss of protein (i.e. liver failure and inability to make albumin or kidney issues and proteinuria).

The description cooresponds to rhabdomyolysis which is excessive breakdown of skeletal muscle tissue that can lead to excessive release of myoglobin into the blood which causes myoglobinuria and kidney damage. Rhabdomyolysis can be precipitated by overexertion (such as a triathalon) and commonly presents with weakness and muscle tenderness and may also present with shortness of breath due to fluid buildup in the lungs.

Rhabdomyolysis will present with elevations in creatinine kinase as well as myoglobin, but it is the elevated myoglobin which causes the symptoms and acute kidney injury as seen in this patient. Creatinine kinase elevation causes no toxic effects, even though it occurs, as reported here.

Here is another article about rhabdomyolysis as it is not covered in depth in First Aid.

Ligation of the internal iliac artery is used to stop postpartum uterine bleeding while preserving fertility as the ovarian arteries provide collateral circulation (FA2020 p640).

Here is an image showing the uterine artery coming off the internal iliac with the ovarian artery collateral.

Other answers:

• The external iliac gives rise to the femoral artery, inferior epigastric artery, and the deep circumflex iliac artery
• The internal pudendal artery supplies the external genetalia and perineum via arteries such as the inferior rectal artery (anal canal BELOW the pectinate line), perineal artery, and ldorsal/deep arteries of the clitoris or dorsal/deep arteries of the penis
• The median sacral artery is small and supplies the coccyx/sacrum/lumbar vertebrae
• The obturator artery is a branch of the internal iliac which gives off the pubic branch (supplies pelvic muscles) and acetabular branch (supplies head of the femur)

The image shown is one of asbestosis (asbestos bodies resemble dumbbell, as seen here and found FA2020 p677). Aside from the image, he also has the major risk factor of asbestosis of working in a shipyard. Asbestosis typically affects the lower lobes of the lungs (hence the bibasilar crepitant crackles) and carries the ability to cause reticulonodular pulmonary infiltrates / fibrosis.

Similar to the pathology behind silicosis fibrosis, alveolar macrophages respond to aesbestos and release fibrogenic factors.

Alveolar macrophages phagocytize foreign materials, release cytokines and alveolar proteases.

Type I pneumocytes make up the alveolar lining, and Type II pneumocytes generate surfactant and can proliferate into Type I pneumocytes in response to alveolar damage. Kulchitsky cells are cells of origin of small cell lung cancer. Clara cells (now called club cells) are nonciliated bronchiolar exocrine cells that secrete a component of surfactant, degrade toxins, and act as reserve cells.

The description of symptoms (right blown pupil, difficulty in eye movement) coorespond with damage to the oculomotor nerve. In this section, letter A is labelling the oculomorot nerve.

Here is a diagram of the middle cranial fossa coronal section labelled. Here is another diagram.

Mycobacterium leprae likes cool temperatures (FA2020 p141)

Mycobacterium leprae is an acid-fast bacteria which can cause two skin manifestations:

• Lepromatous presents diffusely over the skin and with leonine facies and is more serious with a largely Th2 response and high bacteria load
• Tuberculoid (what our patient has) presents with a few hypoesthetic hairless skin plaques with a largely Th1 response and low bacteria load

Leprosy likes cool temperatures so it infects skin and superficial nerves. Even without knowing the organism, the link could also be potentially inferred!

Struvite stones (ammonium magnesium phosphate) commonly form staghorn caliculi.

Other clues in the question stem which point to struvite stones:

• Bacteria in the urine - struvite stones are caused by infections with urease positive bacteria (Proteus mirabilis, Staph saprophyticus, Klebsiella)
• High urine pH - because urease positive organisms produce ammonia, this will alkalinize the urine and contribute to formation of struvite stones

FA2020 p598 has different types of kidney stones.

Cysteine and uric acid stones are both treated with alkalinization of the urine and more associated with acidic urine. Cysteinuria, though it is associated sometimes with staghorn caliculi, is also hereditary, begins in childhood, and is not associated with bacteriuria. Calcium oxalate and calcium phosphate stones are less often associated with staghorn caliculi.

TL;DR: The proper formation of granulomas to wall off TB requires CD4 Th1 cells and marcophages

TB (mycobacterium tuberculosis) begins its life cycle inside of the lungs by being phagocytized by alveolar macrophages abd undergoing intracellular growth and replication within the macrophages. NONactivated macrophages lack the ability to kill TB. In a normal person, some of the macrophages will present TB antigens to CD4 cells and secrete IL12, inducing differentiation to Th1 cells which will then begin the process of granuloma formation. No CD4 T-lymphocytes means no activation of macrophages for granuloma formation, so the macrophages will have deficient function.

FA2020 p217 has the steps of granuloma formation:

• APCs present antigens to CD4 helper T-cells and secrete IL12 to cause differentiation into Th1 cells
• Th1 cells secrete IFNgamma to activate macrophages and induce granuloma formation
• Activated macrophages have better intracellular killing of pathogens such as TB and will increase cytokine secretion (e.g. TNFalpha) to cause formation of epitheliod macrophages and giant cells
• TNFalpha is necessary for maintenance of granulomas

NOTE: Langhans giant cells are formed by activated macrophages after granuloma formation has been already been initiated

This requires knowledge of MOA for phosphodiesterase inhibitors (which are also used for erectile dysfunction). All phosphodiesterase inhibitors will inhibit phosphodiesterase, which normally catalyzes hydrolysis of cAMP or cGMP, so they will work by increasing cAMP/cGMP levels! [FA2020 p246]

NOTE: do not get confused by the addition of NO as an answer, though arteriole dilation by phosphodiesterase inhibitors works in part by enhancing NO activity on smooth muscle, it does not increase the concentration of NO. NO triggers increased cGMP to dilate smooth muscles, and phosphodiesterase inhibitors prevent breakdown of this cGMP, so they work in synergy!

I love this question because we are all obviously trained radiologists...

In reality, rather than identifying every X-ray given and trying to match it to the question stem, the best way to approach this question is to identify what his most likely issue(s) and match to the general characteristic of an X-ray, going to the X-rays looking for these characteristics.

He is an alcoholic with foul smelling (ding anaerobic) sputum. Because he is an alcoholic he is at risk for aspiration pneumonia and anaerobic pulmonary abscesses from aspiration (which is why they mentioned the bouts of blacking out). So what are the characteristics of these diseases? Aspiration pneumonia is a lobar pneumonia which would present with lobar infiltration (see here for example). Pulmonary abscess would present with cavitation and an air-fluid line (see here for example with air fluid level pointed out and here for cavitation/abscess pointed again).

Thinking of this now approach the X-rays looking for specific findings. One has the air fluid level and cavitation, so that is the answer (it is an abscess). None of the others have lobar infiltrate and are either more diffuse or hilar so they should be ruled out.

Water does not require transport proteins or energy for absorption, and transepithelial transport means it must go through the epithelial cells. C is the best match.

This is neonatal physiologic jaundice (FA2020 p393), which is primarily due to immature UDP-gluconuryosyltransferase causing an unconjugated bilirubinemia. The mechanism is decreased conjugation of bilirubin.

Answering this question requires you understand the mechanism of osteoclast stimulation by parathyroid hormone (FA 2020 p332).

Parathyroid hormone stimulates osteoclases indirectly by stimulating the release of RANKL bu osteoblasts which will bind to RANK receptor on osteoclasts and stimulate the resorption of bone. This is a paracrine process because paracrine signaling refers to stimulation by neighboring cells (short distances).

The first thing to look at is potassium, which would decrease because insulin facilitates intracellular shift of potassium (which is why it is used as a treatment for hyperkalemia!). This leaves only two potential answers!

The next thing I immediately noticed was that our patient's labs indicated anion gap metabolic acidosis (likely due to diabetic ketoacidosis). Administration of insulin would improve this condition, and one of the main things that would occur is correction of acidosis, so pH would increase. The other parts of the answer also make sense, as bicarbonate begins to return to normal with the increase in pH and less necessity for use in buffering, BUN decreases as the kidney damage occurring can be mostly reversed, and blood CO2 increases because there is no longer the need for respiratory compensation of the metabolic acidosis.

TL;DR: You want the most sensitive test first to rule out the disease in negatives (least likelihood of false negative) and the most specific test next to "rule in" only true positives (least likelihood of false positives) [FA2020 p257]

The way I always think of sensitivity and specificity is in relation to false negatives and false positives.

• High Se N setivity means you are less likely to have false Negatives (someone who has the disease but tests negative)
• High s P eceificity means you are less likely to have false Positives (someone who tests positive but does not have the disease)

In this question, you want to ensure you are only treating those who actually have the disease, or in other words that you want to minimize your false positives. The best way to do this is maximize sPecificity. Test 1 has 100% specificity meaning it will have essentially NO false positives which is great so we definitely want to use it (eliminating all but two options)! The better way to ensure you are catching as many cases as possible while still only getting true positives is to test with test 3 first, which has a much higher sensitivity. That way we are ruling out disease in the negatives of test 3. This also adds to our ability to only truly treat those with disease as we have ruled out disease in our first negative population, then we test the positives to "rule in" disease with a highly specific test.

The issue with using Test 1 first and only testing the positives is we know the positives from test 1 are likely true positives, as the highly specific test would have a basically zero false positive rate. At that point there would be no point in testing with test 3, as we have basically a true positive population. The issue is we have missed a lot of diseased due to the low sensitivity and high false negative rate of test 1.

Another way to think of this is to remember the formulas (as seNsitivity contains false Negatives, and sPecificity contains false Positives in the formulas; see FirstAid):

• sensitivity = true positive / (true positive + false negative) = 1 - false negative rate --> higher sensitivity means less rate of false negatives
• specificity = true negative / (true negative + false positive) = 1 - false positive rate --> higher specificity means less rate of false positives

SPIN/SNOUT also helps to remember that specific tests rule in disease, and sensitive tests rule out disease

This is G6PD deficiency. (FA2020 p422)

G6PD deficiency causes a hemolytic anemia when individuals are exposed to antimalarials due to the increased oxidative stress. This is due to the deficiency in replenishing NADPH which is necessary to replinish reduced glutathione which aids in quenching free radicals.

Propanolol is a nonselective beta blocker:

• Blockade of beta-1 receptors: beta-1 typically cause an increase in heart rate, so blockade causes decrease in heart rate and contractility. CO = HR x SV so there is an overall decrease in cardiac output
• Blockade of beta-2 receptors: beta-2 receptors normally cause relaxation of smooth muscle and vasodilation, so blockade causes constriction and therefore increases total peripheral resistance (decreased radius leads to increased resistance)

The key to answering this is that she seems unconcerned with her symptoms, which is a hallmark of conversion disorder (la belle indifference) [FA2020 pg 566]

Illness anxiety disorder would be preoccupation with having a certain illness, and inability to be reassured when there are negative findings.

Depersonalization/derealization is a dissociative disorder and "out of body experience" with a feeling of detachment from the body or environment.

Brief psychotic disorder would present more likely with delusions, hallucinations, or some other characteristic of psychosis.

PTSD would present after an extremely traumatic event when symptoms such as anxiety, flashbacks, hyperarousal, and nightmares persist for greater than 1 month after the event.

TL;DR: Renal cell carcinoma can present with polycythemia (due to increased erythropoietin) and hypercalcemia (due to PTHrP) [FA2020 p228]

So the question is what is the primary cancer? He has two tumor locations (kidney and lungs), which could be primary or from metastases.

I narrowed it down to metastatic renal cell carcinoma and bronchogenic squamous cell carcinoma (see below). The only other infoemation really given that could allow us to distinguish is the lab values indicating paraneoplastic syndromes. These are both known to cause paraneoplastic syndromes which can cause hypercalcemia. So focusing on the polycythemia, this is more specific for renal cell carcinoma because no lung cancer secretes EPO.

I eliminated undifferentiated carcinoma because it is too nonspecific and metastatic transitional cell carcinoma because it is rare in the kidney (with no paraneoplastic syndrome typically associated which could cause the lab abnormalities) and there is no mention of bladder.

Multiple myeloma can have renal involvement but does not typically involve the lungs and would present with bone lytic lesions and anemia rather than polycythemia. [FA2020 p431]

Oral rehydration therapy commonly consists of sugar/electrolyte water because of the ability to utilize the sodium glucose symporter. Where sodium goes, water follows, so by hydrating with this mixture it allows for an osmotic "pull" of water into the intestines.

Here is an article with more detail and a pretty diagram: https://basicmedicalkey.com/therapy-of-viral-gastroenteritis/

TL;DR: T-cells are primarily responsible for both acute (weeks to months) and chronic (months to years) rejection; this would be acute rejection [FA2020 p119]

Hyperacute rejection (minutes): from pre-formed antibodies in the recipient which trigger an immune response in the recipient via complement activation (Type II hypersensitivity)

Acute Rejection (weeks to months): recipient T-cells recognize donor MHC on donor dendritic cells (Type IV hypersensitivity); humoral component (Type II hypersensitivity) to a lesser extent AFTER the T-cells have recognized the MHC as foreign

Chronic (months to years): recipitent T-cells recognize alloantigens [which are antigens which would be self in a normal tissue in the donor, but are recognized as foreign in the recipient] presented by recipient dendritic cells (Type IV hypersensitivity); humoral component (Type II hypersensitivity) AFTER the T-cells have recognize the MHC as foreign

Penicillin can cause a direct Coombs + autoimmune hemolytic anemia

The Direct Coomb's test involves anti-Ig antibody (Coombs reagent) added to patient’s RBCs. RBCs agglutinate if the RBCs are already coated with antibodies (indicating that the body is making antibodies that bind the RBCs). RBCs tagged with antibodies are destroyed in the spleen. Penicillin is thought to act as a hapten binding with proteins on the RBCs and triggering an antibody response against the penicillin-RBC complex [FA2020 p423]

TL;DR: This is Ewing sarcoma because it is a young boy with small blue cell bone tumor in the diaphysis of the femur

Ewing sarcoma is a malignant bone tumor common in young boys <15y.o. typically found in the diaphesis (middle) of long bones (particularly femur) or pelvic flat bones. It is a small blue cell tumor, meaning the descriptor of small, uniform, hyperchromatic cells with high nucleus:cytoplasm ratio. It also has an "onion skin" periosteal reaction in the bone (described as tissue surrounded by concentric layers of reactive bone in the question). Not mentioned is the association with t(11;22). [FA 2020 p 464]

Why the others are wrong:

• Chondrosarcoma is a tumor of malignant chondrocytes (catilage) and found mainly in the pelvis, proximal fever, and humerus
• Eosinophilic granuloma is is a rare, benign tumor-like disorder characterized by clonal proliferation of Langerhans cells and the most common varient of Langerhans cell histiocytosis.Would likely say something about Birbeck granules in the stem and would have associated symptoms such as rash [FA 2020 p434]
• Multiple myeloma is a plasma cell dyscrasia [FA 2020 p431] with overproduction of (typically) IgG. Characteristics include CRAB - hyperCalcemia, Renal involvement, Anemia, Back/Bone pain due to punched out lytic bone lesions (typically of the spine)
• Nephroblastoma/Wilm's Tumor is the most common renal malignancy of early childhood and presents as a flank mass [FA 2020 p 606]
• Osteosarcoma (or osteogenic sarcoma) is a primary bone tumor common in men <20. It is typically found in the metaphysis (tips) of long bones. Histology shows pleiomorphic osteoid producing cells. On X-ray you would potentially see a Codman triangle (elevation of periosteum) or sunburst pattern
• Small lymphocytic lymphoma is essentially the same thing as chronic lymphocytic leukemia. It is considered a non-Hodgkin lymphoma of B-cells and the most common leukemia of adults (as CLL). Smudge cells would likely be seen on peripheral blood smear. It would not likely present as an osteolytic lesion and is unlikely in children. [FA2020 p432]

Niemann-Pick is a lysosomal storage disease that is a deficiency in sphingomyelinase that leads to a buildup of sphingomyelin (Niemann picks his nose with his sphinger)

Sphingomyelinase is considered a lysosomal hydrolase

Scurvy is the deficiency in Vitamin C. Vitamin C is necessary for hydroxylation of proline and lysine residues in collagen. Prolyl hydroxylase is responsible for the hydroxylation of proline (see this Wikepedia article)

This individual has active Hepatitis B, as evidenced by their Hepatitis B surface antigen positivity. Hepatitis B virus productively infects hepatocytes. The CD8 cells will thus attack the hepatocytes.

Another way of approaching this question is to notice AST and ALT elevation are typically indicative of hepatocyte damage.

Ito cells are the same thing as stellate cells, and their primary function is to store vitamin D and fat and produce ECM when activated. Kupffer cells are the liver's macrophages. Bile duct epithelium is not infected in hepatitis.

ANG-II (angiotensin II) preferentially constricts the efferent arteriole. (FA2020 p588) This preserves GFR by the "back pressure" pushing filtration to occur.

ACE inhibitors block the conversion of ANG-I to ANG-II.

Here is a good diagram.

And here is a labelling of the parts of the glomerulus.

I am assuming this is just something we are expected to know; tubular reabsorption requires the most oxygen because it would consume the most ATP out of the processes in the kidney?

So I hate this question because you can know what the diagnosis is and still miss it.

TL;DR: This is lead poisioning, so there is basophilic stippling in a peripheral blood smear [BUT ringed sideroblasts would also be found in the bone marrow]

Why this is lead poisoning: (FA2020 p425)

• Microcytic Anemia (caused by lead inhibition of ferrocheletase and ALA dehydratase)
• Environmental exposure (ammunition at the range, he is an officer)
• GI effects (crampy abdominal pain)
• Neurological effects (headache, irritability, distractability, forgetful, motor weakness)

Why it is NOT the other answers:

• Auer rods - characteristic of acute myelogenous leukemia which would present with pancytopenias (his WBCs are normal) along with circulating myeloblasts on peripheral smear; median age onset 65 years and he has no risk factors
• Oval Macrocytes - in macrocytic anemias (B12 or folate deficiency), this is microcytic as indicated by MCV
• Pleomorphic lymphocytes - occur in chronic lymphocytic leukemias and infectious mono, both which have different symptomotologies
• Ringed sideroblasts - are from lead poisoning but are in the bone marrow
• Scistocytes - characteristic RBC which has been through a clogged vessel and sheared off, found in microangiopathic hemolytic anemias (MAHAs) like thrombotic microangiopathies like TTP and HUS (typically normocytic anemia and different presentation; a question would likely give you more info on the thrombolytic pathway if they wanted you to choose this; we didn't even get a platelet count here)
• Target Cells: found in HbC disease (glutamic acid to lysine in hemoglobin, causes extravascular hemolysis), liver disease, asplenia, and Thalassemia (deletions in either alpha or beta chain of hemaglobin, causes anemia that would be present from childhood and would not have neuro symptoms)

This ratio is used to determine appropriate production of lung surfactant, so this baby would not have appropriate production of surfactant if birthed at the time of the ratio calculation. It would go into neonatal respiratory distress syndrome.

TL;DR: surfactant decreases lung recoil, so the lack of surfactant in this baby will cause an increased recoil which will decrease the functional residual capacity (FA 2020 p661-662)

Surfactant is necessary to decrease surface tension of alveoli and increase compliance of the lungs (remember when the lungs have greater compliance, this makes the lungs easier to fill). Surfactant also helps to prevent alveolar collapse as the lack of surfactant allows there to be varying surface tensions between large and small alveoli (Law of Laplace), so lack of surfactant would lead to widespread atelectasis (alveolar collapse). Because surfactant serves to decrease these forces which normally favor collapse of the lung, it also serves to decrease the lung recoil.

Lack of surfactant in a baby = increased alveolar surface tension, lower compliance, more alveolar collapse, more recoil (less residual volumes)

Total lung capacity is unchanged because with enough force you can still expand the lungs to full capacity.

This is my best interpretation with a source and paragraph from the source listed:

In anemia, hemoglobin available is decreased. This causes decreased oxygen binding, and ultimately less oxygen is available for release onto tissues.

• PaO2 will be normal-ish because the arterial blood will still equilibrate in the lungs even though the hemoglobin binding is decreased (think of CO poisoning where PaO2 looks normal).
• Arterial O2 content is actually decreased because there is less oxygen total available (less hemoglobin bound to oxygen)
• Mixed venous O2 content (%) is decreased for a similar reason and also for the reason listed below
• Venous PO2 is slightly decreased because there is higher oxygen extraction at tissues due to the compensatory mechanisms from less total O2 being delivered and less O2 being unloaded (since there is less hemaglobin bound O2 in the first place in anemia)
• PCO2 is normal-ish for similar reasons to the first bullet

"The circulatory adjustments in response to anemia will be similar to those of the preceding case. In order to maintain tissue oxygen consumption at baseline levels associated with a normal oxygen carrying capacity of blood, the reduction in oxygen delivery will lead to an increase in capillary perfusion, and oxygen extraction will increase. Arteriolar dilation and viscosity reduction (for the case of a reduction in Hct) will cause blood flow and oxygen delivery to increase. Both oxygen extraction and oxygen delivery will continue to increase until the oxygen requirements of the tissues are met or until the capacity to increase oxygen extraction and delivery has been reached. The resulting situation is one in which venous oxygen content and PvO2 are less than normal. Since PaO2 is normal for all the anemic situations considered, this defect is not sensed by the respiratory chemoreceptors. Thus, increasing the inspired oxygen fraction is not helpful except for the case of CO poisoning, where high inspired oxygen (e.g., 100% oxygen at ambient barometric pressure or placement of the subject into a hyperbaric chamber) competes with CO binding at the heme site (recall Haldane's first law)." - https://www.ncbi.nlm.nih.gov/books/NBK54113/

Many opioids (like morphine) are potent histamine releasers, which can cause puritis and anaphylactoid reactions (such as seen in this patient with the facial flushing, drop in blood pressure and corresponding increase in heart rate). Puritis is actually a common side effect of morphine.

Source: First Aid and

https://www.ncbi.nlm.nih.gov/pubmed/22417016