A 12-year-old boy is found on a routine auditory screening to have mild high frequency hearing impairment. On exam, he has no ear pain, no focal neurological deficits, and no cardiac murmurs. He has not had any recent illness. Laboratory studies show: Serum: Creatinine: 0.7 mg/dl Protein: 3.8 g/dl Antistreptolysin O titer: 60 Todd units (12-166 normal range) Urinalysis: Microscopic heme Protein: 4+ RBCs: 6/hpf A kidney biopsy is taken. Which of the following findings is most characteristic of this patient’s disease?

“Basket-weave” pattern of basement membrane on electron microscopy

Thickened “tram-track” appearance of basement membrane on electron microscopy

“Spike and dome” appearance on electron microscopy

Crescent-moon shapes on light microscopy

Large eosinophilic nodular lesions on light microscopy

A 22-year-old man comes to the physician because of a 2-week history of cough and decreased urination. The cough was initially nonproductive, but in the last few days he has coughed up small amounts of blood-tinged sputum with clots. He has not had any fevers, chills, or weight loss. He has smoked one pack of cigarettes daily for 5 years. Pulse is 115/min and blood pressure is 125/66 mm Hg. Physical examination shows dried blood around the lips. Serum studies show a creatinine of 2.9 mg/dL. Results of a serum antineutrophil cytoplasm antibody test are negative. A biopsy specimen of the kidney is most likely to show which of the following light microscopy findings?

Fibrin crescents in Bowman space

Thinning of the basement membrane

Expansion of the mesangial matrix

Enlarged and hypercellular glomeruli

Neutrophilic infiltration of the capillaries

A 20-year-old man comes to the clinic complaining of fever and a sore throat for 5 days. He receives oral penicillin from his primary doctor. After a day of antibiotic treatment, he developed gross hematuria. As a child, he recalls having multiple episodes of hematuria. The vital signs are within normal limits. On physical examination, pharyngeal edema and cervical lymphadenopathy are present. His laboratory examination reveals the following: WBC 11,000/mm3 Neutrophils 76% Lymphocytes 23% Eosinophils 1% Platelets 150,000/mm3 Hemoglobin 14 g/dL Hct 41.2% BUN 16 mg/dL Creatinine 0.9 mg/dL ASO titer 100 Urinalysis shows hematuria but no proteinuria. Immunofluorescence shows granular IgA immune complex deposits in the mesangium. Hepatitis B, hepatitis C, and HIV serology are negative. ASO titers and C3 levels are within normal limits. What is the most likely diagnosis?

Penicillin-induced hypersensitivity reaction

A 13-year-old boy is brought to the physician because of swelling around his eyes for the past 2 days. His mother also notes that his urine became gradually darker during this time. Three weeks ago, he was treated for bacterial tonsillitis. His temperature is 37.6°C (99.7°F), pulse is 79/min, and blood pressure is 158/87 mm Hg. Examination shows periorbital swelling. Laboratory studies show: Serum Urea nitrogen 9 mg/dL Creatinine 1.7 mg/dL Urine Protein 2+ RBC 12/hpf RBC casts numerous A renal biopsy would most likely show which of the following findings?

Granular deposits of IgG, IgM, and C3 on immunofluorescence

Effacement of podocyte foot processes on electron microscopy

Splitting and alternating thickening and thinning of the glomerular basement membrane on light microscopy

Mesangial IgA deposits on immunofluorescence

"Spike-and-dome" appearance of subepithelial deposits on electron microscopy

A 35-year-old woman who was recently ill with an upper respiratory infection presents to the emergency department with weakness in her lower limbs and difficulty breathing. Her symptoms began with a burning sensation in her toes along with numbness. She claims that the weakness has been getting worse over the last few days and now involving her arms and face. Currently, she is unable to get up from the chair without some assistance. Her temperature is 37.0°C (98.6°F), the blood pressure is 145/89 mm Hg, the heart rate is 99/min, the respiratory rate is 12/min, and the oxygen saturation is 95% on room air. On physical examination, she has diminished breath sounds on auscultation of bilateral lung fields with noticeably poor inspiratory effort. Palpation of the lower abdomen reveals a palpable bladder. Strength is 3 out of 5 symmetrically in the lower extremities bilaterally. The sensation is intact. What is the most likely diagnosis?

Acute disseminated encephalomyelitis

A 19-year-old woman is brought to the emergency room by her mother. She found her daughter pale, cold to the touch, and collapsed next to her bed earlier this morning. The patient has no previous medical or psychiatric history, but the mother does report that her daughter has not had her periods for the last 3 months. In the emergency department, the patient is alert and oriented. Her vitals include: blood pressure 80/60 mm Hg supine, heart rate 55/min. On physical examination, the patient appears pale and emaciated. A urine pregnancy test is negative. She is suspected of having an eating disorder. Which of the following treatment options would be contraindicated in this patient?

Selective serotonin reuptake inhibitors

A 12-year-old boy comes to the physician for the evaluation of intermittent blood-tinged urine for several months. Four months ago, he had an episode of fever and sore throat that resolved without treatment after 5 days. During the past 2 years, he has also had recurrent episodes of swelling of his face and feet. 5 years ago, he was diagnosed with mild bilateral sensorineural hearing loss. His brother died of a progressive kidney disease at the age of 23. The patient appears pale. His temperature is 37°C (98.6°F), pulse is 70/min, and blood pressure is 145/85 mm Hg. Slit lamp examination shows a conical protrusion of both lenses. Laboratory studies show a hemoglobin concentration of 11 g/dL, urea nitrogen concentration of 40 mg/dL, and creatinine concentration of 2.4 mg/dL. Urinalysis shows: Blood 2+ Protein 1+ RBC 5–7/hpf RBC casts rare Which of the following is the most likely underlying cause of this patient's symptoms?

Autosomal-recessive kidney disease

Type II hypersensitivity reaction

Nephritic syndrome disorders for USMLE Step 2 CK: High-Yield Pathology Lessons

Nephritic Syndrome - PHAROH's Revenge

Glomerular inflammation causing hematuria, hypertension, oliguria, and azotemia.

📌 PHAROH Mnemonic:

Post-streptococcal GN: Common cause in children.
Hypertension: Due to salt/fluid retention.
Azotemia: ↑ BUN & Creatinine.
RBC casts in urine: Pathognomonic for glomerular bleeding.
Oliguria: Low urine output (< 500 mL/day).
Hematuria: Cola-colored urine.

Nephritic Syndrome Histopathology Patterns

⭐ Post-streptococcal GN shows a "lumpy-bumpy" granular pattern on immunofluorescence due to IgG, IgM, and C3 deposition along the GBM and mesangium.

Post-Infectious GN - Sore Throat, Sore Kidney

Etiology: Follows Group A β-hemolytic Strep (GAS) infection, typically pharyngitis (1-3 wks prior) or impetigo (3-6 wks prior).
Pathogenesis: Type III hypersensitivity reaction. Deposition of immune complexes (IgG, IgM, C3) against streptococcal antigens (e.g., SpeB) in glomeruli.
Clinical: Acute nephritic syndrome triad:
- Periorbital edema
- Cola-colored urine (hematuria)
- Hypertension
Labs: ↑ ASO or anti-DNase B titers; ↓ C3 levels.
Microscopy:
- LM: Diffusely hypercellular, proliferative glomeruli with neutrophils.
- IF: Granular, "starry sky" deposits of IgG and C3.

EM of post-streptococcal glomerulonephritis with humps

⭐ Classic finding: Subepithelial electron-dense deposits ("humps") on EM.

IgA Nephropathy - Berger's Recurring Bleed

Most common primary glomerulonephritis globally. Affects children and young adults.
Presents as episodic gross hematuria, often concurrent with a URI or GI infection (synpharyngitic hematuria).
Pathogenesis involves mesangial deposition of aberrantly glycosylated IgA1 immune complexes.
Serum complement levels are typically normal.
Often benign and self-limiting, but 20-40% may progress to chronic renal failure over decades.

⭐ Henoch-Schönlein Purpura (HSP) is the systemic vasculitis form of IgA nephropathy.

Severe Syndromes - Crescents & Heredity

Rapidly Progressive Glomerulonephritis (RPGN): Characterized by crescent formation in Bowman's space, leading to rapid renal failure.
Alport Syndrome: Hereditary nephritis from a Type IV collagen mutation (X-linked). Presents as a triad of renal disease, sensorineural deafness, and ocular abnormalities (e.g., lenticonus).
- EM shows GBM splitting, creating a "basket-weave" appearance.
- 📌 Mnemonic: "Can't see, can't pee, can't hear a bee."

Alport Syndrome: EM of GBM basket-weave appearance

⭐ Goodpasture syndrome is caused by autoantibodies against the alpha-3 chain of type IV collagen in the glomerular and alveolar basement membranes.

High‑Yield Points - ⚡ Biggest Takeaways

Nephritic syndrome is a clinical pentad: hematuria (RBC casts), hypertension, azotemia, oliguria, and mild proteinuria (<3.5 g/day).

Post-streptococcal GN follows a GAS infection; see subepithelial "humps" and low C3.

IgA nephropathy (Berger disease) is the most common GN, with mesangial IgA deposits after a mucosal infection.

Rapidly progressive GN (RPGN) is defined by crescents in Bowman's space, causing rapid renal failure.

Alport syndrome is an X-linked defect in Type IV collagen causing nephritis, deafness, and ocular defects.

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