PHARM 101
A 64-year-old woman with hypertension and diabetic nephropathy is started on lisinopril. Two weeks later, her serum creatinine increases from 1.1 to 1.8 mg/dL. She also develops hyperkalemia. Which renal vascular change best explains these findings?
Answer: Efferent arteriolar dilation
Why?
-> ACE inhibitors ↓ angiotensin II → ↓ efferent arteriolar constriction → ↓ glomerular hydrostatic pressure → ↓ GFR.
Trap: NSAIDs constrict the afferent arteriole. ACE inhibitors dilate the efferent arteriole.
ACEi = “Efferent exits.”
-A 67-year-old man with hypertension develops sudden-onset chest pain. ECG shows ST elevations in leads II, III, and aVF. Which coronary artery is most likely occluded?
Answer: RCA (Right coronary artery)
Why?
-> Inferior wall = usually RCA.
Trap: If the vignette also gives hypotension + bradycardia, think RCA → AV nodal ischemia.
A 6-month-old boy has recurrent bacterial and viral infections. He has markedly decreased levels of all immunoglobulin classes. Flow cytometry shows absent mature B cells. Which gene is most likely mutated?
Answer: BTK
Diagnosis: X-linked agammaglobulinemia.
Why?
-> Bruton tyrosine kinase is required for B-cell maturation.
Step 1 clue:
Male infant + recurrent infections after ~6 months + absent B cells = BTK.
A 47-year-old man with bipolar disorder treated with lithium develops polyuria and polydipsia. Serum sodium is 151 mEq/L and urine osmolality is low. Administration of desmopressin produces minimal change in urine concentration. Which mechanism is most likely responsible?
Answer: Decreased responsiveness of collecting duct principal cells to ADH
Why?
-> Lithium enters principal cells through ENaC and interferes with ADH signaling → ↓ aquaporin-2 insertion → nephrogenic diabetes insipidus.
Trap:
Central DI → responds to desmopressin
Nephrogenic DI → does NOT
Treatment: amiloride can block lithium entry through ENaC.
A 24-year-old woman presents with pleuritic chest pain and dyspnea 3 days after giving birth. ECG shows sinus tachycardia. Chest x-ray is normal. She is hemodynamically stable. Which finding would most strongly support the suspected diagnosis?
Answer: Filling defect in a pulmonary artery on CT pulmonary angiography
Diagnosis: (PE) Pulmonary embolism.
Trap: A normal CXR does not exclude PE.
A patient with cirrhosis develops confusion and asterixis. What substance accumulates and what medication is used for treatment?
Answer: Ammonia → lactulose, Hepatic Encephalopathy
Why?
-> Cirrhosis → impaired hepatic detoxification → accumulation of ammonia.
Ammonia crosses the BBB → astrocyte dysfunction → altered mental status + asterixis.
Lactulose traps NH₃ as NH₄⁺ in the colon and promotes its excretion.
Step 1 pearl:
Asterixis + cirrhosis = hepatic encephalopathy
A 35-year-old woman taking sertraline is prescribed linezolid for a resistant bacterial infection. Several days later, she develops agitation, diaphoresis, diarrhea, hyperreflexia, and inducible clonus. Which mechanism best explains her symptoms?
Answer: Excess serotonergic activity
Why?
-> Linezolid has MAO-inhibiting activity. Combined with an SSRI → excessive serotonin.
Trap: Severe rigidity + hyporeflexia suggests NMS, not serotonin syndrome.
Step 1 pearl:
Serotonin syndrome = clonus + hyperreflexia.
A 43-year-old man has hemoptysis, weight loss, and night sweats. Chest x-ray shows an upper-lobe cavitary lesion. Biopsy shows granulomas with central caseous necrosis. Which immune response is primarily responsible?
Answer: Th1-mediated macrophage activation via IFN-γ
Why?
-> TB requires cell-mediated immunity.
Trap: Th2 → eosinophils/IgE, not TB control.
A 33-year-old woman has hypertension, muscle weakness, and polyuria. Labs show K⁺ 2.7 mEq/L, HCO₃⁻ 32 mEq/L, renin low, and aldosterone low. Which abnormality is most likely present?
Answer: Increased ENaC activity
Diagnosis: Liddle syndrome.
Why?
-> ENaC gain-of-function → ↑ Na⁺ reabsorption → hypertension.
Then:
↑ Na⁺ reabsorption → ↑ K⁺ secretion → hypokalemia
and ↑ H⁺ secretion → metabolic alkalosis
Because ENaC is activated independently of aldosterone: renin ↓ + aldosterone ↓
patient has episodic headaches, sweating, palpitations, and severe hypertension. What tumor is likely responsible and what metabolic pathway is being affected?
Answer: Pheochromocytoma → catecholamine excess
Why?
-> Catecholamine-secreting tumor → episodic:
Headache + sweating + palpitations + hypertension
Tumor arises from chromaffin cells of the adrenal medulla.
Produces:
Diagnosis: elevated metanephrines.
Step 1 pearl:
Think MEN2 when you see pheochromocytoma.
A 61-year-old man with atrial fibrillation taking warfarin presents with intracranial hemorrhage. INR is 7.2. Which of the following is the most appropriate treatment?
Answer: 4-factor PCC (Prothrombin complex concentrate) + IV vitamin K
Why?
-> PCC immediately replaces factors II, VII, IX, X, while vitamin K restores endogenous synthesis.
Trap: Fresh frozen plasma can be used if PCC isn't available, but PCC is preferred for rapid reversal.
A 70-year-old man develops sudden painless loss of vision in his right eye. Fundoscopic examination shows a pale retina with a cherry-red spot at the macula. Which vessel is most likely occluded?
Answer: Central retinal artery
Why?
-> Retinal ischemia causes diffuse retinal pallor while the macula retains its reddish appearance because it receives some choroidal blood supply.
Step 1 pearl:
“Cherry-red spot” = central retinal artery occlusion
A 31-year-old woman presents with fatigue and petechiae. Labs show Hb 7.2 g/dL, platelets 12,000/mm³, elevated LDH, indirect hyperbilirubinemia, and creatinine 2.0 mg/dL. Peripheral smear shows schistocytes. PT and PTT are normal. Which enzyme is most likely deficient?
Answer: ADAMTS13
Why?
-> TTP = severe ADAMTS13 deficiency → accumulation of ultra-large vWF multimers → platelet-rich microthrombi.
Trap: DIC also causes schistocytes, but:
TTP → normal PT/PTT
DIC → prolonged PT/PTT
-A patient develops loss of pain and temperature sensation bilaterally in the upper extremities. Vibration and proprioception are intact. Which spinal cord structure is most likely damaged?
Answer: Anterior white commissure
Why?
-> Pain/temp fibers cross through the anterior white commissure after entering the spinal cord.
Diagnosis: Syringomyelia.
Classic association: Cervical enlargement → cape-like distribution.
A 43-year-old woman with schizophrenia treated with haloperidol develops fever, severe generalized rigidity, altered mental status, and autonomic instability. CK is 12,000 U/L. Which of the following mechanisms most directly caused this condition?
Answer: Dopamine D₂ receptor blockade
Why?
-> This is neuroleptic malignant syndrome.
D₂ blockade → dysfunction of dopamine pathways involved in:
Severe muscle rigidity → muscle breakdown → ↑ CK.
Trap: Serotonin syndrome has hyperreflexia/clonus, whereas NMS has “lead-pipe” rigidity.
A 59-year-old woman develops progressive dysphagia to solids and liquids. Endoscopy shows a dilated esophagus without an obstructing mass. Barium swallow shows a “bird-beak” appearance. Which histologic finding is most likely?
Answer: Loss of myenteric plexus ganglion cells
Diagnosis: Achalasia.
Why?
-> Loss of inhibitory neurons → impaired LES relaxation + absent peristalsis.
Association: Increased risk of esophageal squamous cell carcinoma.
A 19-year-old man has recurrent episodes of severe abdominal pain, anxiety, and dark-colored urine. He recently started a barbiturate-containing medication. He has no fever or leukocytosis. Neurologic examination is normal between episodes. Urine testing is positive for porphobilinogen. Which enzyme is deficient?
Answer: Porphobilinogen deaminase
Diagnosis: Acute intermittent porphyria.
Why?
-> ↓ porphobilinogen deaminase → accumulation of ALA and porphobilinogen → neurovisceral attacks.
Trap: No photosensitivity in AIP.
STEP 1 pearl:
Abdominal pain + psychiatric symptoms + neuropathy + dark urine
A 63-year-old man develops sudden weakness of the right arm and leg. Examination shows right-sided hemiparesis and loss of vibration/proprioception on the right. His tongue deviates to the left when protruded. Which artery is most likely affected?
Answer: Left anterior spinal artery/paramedian branches of the vertebral artery
Why?
-> Medial medulla contains:
Therefore:
Left medial medulla → right weakness + right proprioception loss + left CN XII palsy.
Step 1 pearl:
Medial medullary syndrome = “12 + motor + medial lemniscus.”
A young woman develops hemoptysis and hematuria. Labs show rapidly progressive glomerulonephritis. Kidney biopsy shows linear IgG deposition along the GBM. What is the diagnosis, and what is the target antigen?
Answer: Goodpasture Syndrome → anti-α3 chain of type IV collagen
Why?
-> Autoantibodies attack the α3 chain of type IV collagen in:
Therefore:
Hematuria + rapidly progressive GN + hemoptysis
Biopsy:
Linear IgG deposition along the GBM
That's the key distinction.
Compare:
Goodpasture
→ linear IgG
SLE
→ “full house” immune complex deposition
Post-strep GN
→ granular “lumpy-bumpy” deposition
Step 1 memory:
Goodpasture = Good lungs + Good kidneys → anti-GBM