A 60-year-old African American woman presents to her family physician with shortness of breath on exertion. She also describes shortness of breath when she lies down to go to bed at night, as well as recent swelling in her ankles. Past medical history is significant for long-standing hypertension, for which she takes amlodipine and lisinopril. Her temperature is 36.8°C (98.2°F), the heart rate is 90/min, the respiratory rate is 15/min, and the blood pressure is 135/80 mm Hg. The physical exam is significant for JVD, lower extremity pitting edema, laterally displaced PMI, left ventricular heave, bilateral pulmonary crackles, and an S4 heart sound. Chest X-ray demonstrates pulmonary vascular congestion, Kerley B lines, and cardiomegaly. Echocardiogram demonstrates a preserved ejection fraction. Kidney biopsy would likely demonstrate which of the following?

Intimal thickening and medial hypertrophy

Thinning of the intima and media

A 50-year-old man is brought to the hospital after being found unresponsive in his bed in the morning. He is declared dead on arrival in the emergency room. His wife states that he always had uncontrolled hypertension despite being on multiple medications. An autopsy is performed, and the cause of his death is found to be a hemorrhage in his right basal ganglia. On microscopic examination, the branches of the renal artery have concentric endothelial proliferation with prominent narrowing of the lumen resulting in focal ischemia and hemorrhage of the renal parenchyma. Which of the following is most likely related to the findings in this patient?

Raised renin level in the blood

Raised cholesterol level in the blood

Elevated ammonia level in the blood

Raised calcium level in the blood

Elevated C-reactive protein in the blood

A previously healthy 40-year-old woman comes to the physician because of a 3-day history of fever, headaches, and fatigue. She also reports a persistent tingling sensation in her right hand and numbness in her right arm that started this morning. Physical examination shows pallor, mild scleral icterus, and petechiae on her forearms and legs. On mental status examination, she appears confused and is only oriented to person. Laboratory studies show: Hemoglobin 11.1 g/dL Platelet count 39,500/mm3 Bleeding time 9 minutes Prothrombin time 14 seconds Partial thromboplastin time 35 seconds Serum Creatinine 1.7 mg/dL Total bilirubin 2.1 mg/dL A peripheral blood smear shows fragmented erythrocytes. Which of the following is the most likely underlying cause of this patient's condition?

Antibodies against double-stranded DNA

Absence of platelet GpIIb/IIIa receptors

A 53-year-old woman presents with a severe headache, nausea, and vomiting for the past 48 hours. Vitals show a blood pressure of 220/134 mm Hg and a pulse of 88/min. Urinalysis shows a 2+ proteinuria and RBC casts. Which of the following renal lesions is most likely to be seen in this patient?

Acute interstitial nephritis (AIN)

A 62-year-old man comes to the physician because of fatigue and swelling of the lower legs for 3 weeks. One year ago, he had an 85% stenosis in the left anterior descending artery, for which he received 2 stents. He was diagnosed with hepatitis C 5 years ago. He has type 2 diabetes mellitus and arterial hypertension. Current medications include aspirin, metformin, and ramipril. He does not smoke or drink alcohol. His temperature is 37°C (98.6°F), pulse is 92/min, and blood pressure is 142/95 mm Hg. Examination shows 2+ pretibial edema bilaterally. The remainder of the examination shows no abnormalities. Laboratory studies show: Hemoglobin 10.2 g/dL Leukocyte count 6500/mm3 Platelet count 188,000/mm3 Serum Na+ 137 mEq/L Cl− 105 mEq/L K+ 5.2 mEq/L Urea nitrogen 60 mg/dL Glucose 110 mg/dL Creatinine 3.9 mg/dL Albumin 3.6 g/dL HbA1C 6.8% Urine Blood negative Glucose 1+ Protein 3+ WBC 0–1/hpf A renal biopsy shows sclerosis in the capillary tufts and arterial hyalinosis. Which of the following is the most likely underlying mechanism of this patient's findings?

Membranoproliferative glomerulonephritis

A 48-year-old man is brought to the emergency department by his wife because of a 3-day history of increasing confusion and lethargy. He complains of decreased urine output and abdominal pain for the past month. Two months ago, he was hospitalized for pyelonephritis and treated with ceftriaxone. He has a history of chronic hepatitis C. He does not take any medications. He appears pale and irritable. His temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 98/60 mm Hg. On mental status examination, he is oriented to person but not to time or place. Physical examination shows scleral icterus and jaundice. There is 2+ pitting edema of the lower extremities. The abdomen is distended with a positive fluid wave. Laboratory studies show: Hemoglobin 10.1 g/dL Leukocyte count 4300/mm3 Platelet count 89,000/mm3 Prothrombin time 19 sec Serum Urea nitrogen 71 mg/dL Glucose 99 mg/dL Creatinine 3.5 mg/dL ALT 137 mg/dL AST 154 mg/dL Urinalysis shows no abnormalities. The FeNa is < 1%. Ultrasound of the kidneys is unremarkable. Intravenous fluids are administered for 36 hours but do not improve urine output. Which of the following is the most likely cause of the kidney dysfunction in this patient?

Renal interstitial inflammation

A 67-year-old man presents with pain in both legs. He says the pain is intermittent in nature and has been present for approximately 6 months. The pain increases with walking, especially downhill, and prolonged standing. It is relieved by lying down and leaning forward. Past medical history is significant for type 2 diabetes mellitus, hypercholesterolemia, and osteoarthritis. The patient reports a 56-pack-year history but denies any alcohol or recreational drug use. His vital signs include: blood pressure 142/88 mm Hg, pulse 88/min, respiratory rate 14/min, temperature 37°C (98.6°F). On physical examination, the patient is alert and oriented. Muscle strength is 5/5 in his upper and lower extremities bilaterally. Babinski and Romberg tests are negative. Pulses measure 2+ in upper and lower extremities bilaterally. Which of the following is the next best step in the management of this patient?

CT angiography of the lower extremities

Epidural corticosteroid injection

A 70-year-old man is brought to the emergency department by his wife because of lethargy, confusion, and nausea for the past 2 days. He has previously been healthy and has no past medical history. His only medications are a daily multivitamin and acetaminophen, which he takes daily for hip pain. Vital signs are within normal limits. He is disoriented to place and time but recognizes his wife. The remainder of his physical examination shows no abnormalities. Laboratory studies show a hemoglobin concentration of 9.1 g/dL, a serum calcium concentration of 14.7 mg/dL, and a serum creatinine of 2.2 mg/dL (previously 0.9 mg/dL). Which of the following is the most likely underlying mechanism of this patient's condition?

Overproliferation of plasma cells

Increased serum levels of 1,25-hydroxyvitamin D

Excessive consumption of calcium

Excess PTH secretion from parathyroid glands

Renal vascular diseases for USMLE Step 2 CK: High-Yield Pathology Lessons

Hypertensive Nephropathy - Pressure Cooker Kidneys

Pathophysiology: Chronic hypertension → pressure-induced injury to renal arterioles, leading to luminal narrowing and ischemia.
Benign Nephrosclerosis (Chronic HTN):
- Gross: Symmetrically atrophic kidneys with a fine, granular cortical surface.
- Micro: Hyaline arteriolosclerosis (glassy, pink thickening of arteriole walls), leading to glomerulosclerosis, tubular atrophy, and interstitial fibrosis.
Malignant (Accelerated) Hypertension:
- Micro: Fibrinoid necrosis and hyperplastic arteriolosclerosis ("onion-skinning").
- Gross: "Flea-bitten" appearance from petechial hemorrhages.

⭐ Exam Favorite: The pathognomonic finding for malignant hypertension is hyperplastic arteriolosclerosis, described as "onion-skinning" of arterioles due to concentric smooth muscle proliferation.

Renal Hyaline Arteriolosclerosis Micrograph

Renal Artery Stenosis - The Clogged Pipe

Etiology: Narrowing of one or both renal arteries, most commonly due to:
- Atherosclerosis (~90%): Elderly males; involves renal artery ostium.
- Fibromuscular Dysplasia (FMD): Younger females; classic "string of beads" appearance on angiography.
Pathophysiology: Reduced renal blood flow triggers the Renin-Angiotensin-Aldosterone System (RAAS), leading to severe secondary hypertension.

Renal artery fibromuscular dysplasia, "string of beads"

Clinical Clues:
- Resistant hypertension, especially in patients <30 or >55 years.
- Audible abdominal bruit.
- Recurrent "flash" pulmonary edema.
- Acute kidney injury (↑ Cr >30%) after starting an ACE inhibitor or ARB.

⭐ Unilateral stenosis leads to hypertension; bilateral stenosis can cause both hypertension and renal failure, especially with ACE inhibitor use which preferentially dilates the efferent arteriole, dropping GFR.

Thrombotic Microangiopathies - Tiny Clot Chaos

Schistocytes and helmet cells in thrombotic microangiopathy

Pathophysiology: Endothelial injury triggers widespread platelet activation and microthrombi formation in small vessels.
Clinical Triad: Microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ injury (especially kidney and CNS).

Thrombotic Thrombocytopenic Purpura (TTP):
- Cause: ↓ ADAMTS13 activity (autoimmune Ab or genetic). Leads to large vWF multimers that trap platelets.
- 📌 FAT RN Pentad: Fever, Anemia, Thrombocytopenia, Renal failure, Neurologic signs.
Hemolytic Uremic Syndrome (HUS):
- Typical (D+ HUS): Shiga-like toxin (E. coli O157:H7) injures endothelium. Often follows dysentery.
- Atypical (aHUS): Dysregulated complement activation.
- Presents with more prominent acute kidney injury.

⭐ Key diagnostic clue: Peripheral smear shows schistocytes. Unlike in DIC, coagulation studies (PT/PTT) are characteristically normal.

Embolic & Infarctive Disease - Sudden Blockade

Etiology: Thromboembolism from the left heart is the most common cause, often secondary to atrial fibrillation or mural thrombi post-myocardial infarction.
- Other sources include septic emboli (endocarditis) and cholesterol emboli (atheroembolism).
Pathology: Results in wedge-shaped, pale (anemic) infarcts with a base on the cortex and apex pointing to the medulla.
- A thin subcapsular rim of cortex is often spared due to dual blood supply from capsular vessels.
- Microscopy shows coagulative necrosis.
Clinical: Sudden onset of flank pain, hematuria, and fever.
Labs: Markedly elevated serum lactate dehydrogenase (LDH) is a classic finding.

Renal Infarct: Pale, Wedge-Shaped Necrosis

⭐ Renal infarcts are pale (anemic) because the renal arteries are end-arteries with no significant collateral flow. Occlusion leads to ischemic coagulative necrosis without hemorrhage, unlike organs with dual circulation (e.g., lung, liver).

Renal Artery Stenosis is a key cause of secondary hypertension, driven by atherosclerosis in older men or fibromuscular dysplasia in young women.

Malignant hypertension shows fibrinoid necrosis and hyperplastic "onion-skin" arteriolosclerosis, creating a "flea-bitten" kidney appearance.

Thrombotic microangiopathies (TTP/HUS) feature platelet-rich thrombi in glomeruli, causing MAHA and acute kidney injury.

Atheroembolic disease follows vascular procedures, with cholesterol crystal emboli, livedo reticularis, and eosinophilia.

Renal vein thrombosis is a major complication of nephrotic syndrome (especially membranous nephropathy).

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