Nephrology Syllabus

List the main causes of transcellular potassium shifts that alter serum K+ without changing total body K+.

Factors driving K+ INTO cells (lowering serum K+): insulin, β2-agonists, alkalosis. Factors driving K+ OUT of cells (raising serum K+): acidosis (esp. mineral acids), cell lysis, hyperosmolarity, digoxin (Na+/K+-ATPase inhibition), and β-blockade.

Describe the classic ECG progression of worsening hyperkalemia.

Peaked T waves → PR prolongation and P-wave flattening → widened QRS → sine-wave pattern → ventricular fibrillation/asystole. IV calcium gluconate is given first to stabilize the myocardium (it does not lower K+).

What are the emergency treatments to shift and remove potassium in acute hyperkalemia?

Stabilize membrane: IV calcium gluconate. Shift K+ into cells: insulin + glucose, β2-agonist (albuterol), sodium bicarbonate (if acidotic). Remove K+ from body: loop diuretics, cation-exchange resins/binders (patiromer, sodium zirconium), and hemodialysis (definitive).

How do the kidney and gut normally regulate calcium and phosphate via PTH?

PTH (from low serum Ca2+) increases renal Ca2+ reabsorption (distal tubule), decreases phosphate reabsorption (proximal tubule → phosphaturia), and stimulates $1\alpha$-hydroxylase to make active vitamin D ($1,25$-dihydroxyvitamin D), which raises gut absorption of both Ca2+ and phosphate.

Explain the mineral bone disorder of chronic kidney disease (CKD-MBD).

Failing kidneys retain phosphate and cannot make $1,25$-(OH)$_2$ vitamin D → hypocalcemia and hyperphosphatemia stimulate PTH → secondary (then tertiary) hyperparathyroidism and renal osteodystrophy. Elevated FGF-23 rises early. Treatment: phosphate binders, active vitamin D analogs, calcimimetics.

Write the Henderson-Hasselbalch equation for the bicarbonate buffer system.

$$pH = 6.1 + \log_{10}\!\left(\frac{[\ce{HCO3^-}]}{0.03 \times P_{CO_2}}\right)$$ Normal arterial values: $pH = 7.40$, $[\ce{HCO3^-}] = 24$ mEq/L, $P_{CO_2} = 40$ mmHg.

Give the formula for the serum anion gap and its normal range.

$$AG = [\ce{Na+}] - ([\ce{Cl-}] + [\ce{HCO3^-}])$$ Normal is approximately $8{-}12$ mEq/L (correct for albumin: add ~2.5 mEq/L per 1 g/dL albumin below 4). An elevated gap indicates accumulation of unmeasured anions.

Contrast the causes of high-anion-gap versus normal-anion-gap metabolic acidosis (mnemonics).

High anion gap (GOLD MARK / MUDPILES): glycols, oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, ketoacidosis. Normal (hyperchloremic) anion gap (HARDASS/USED CARP): diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors, ureteral diversion, saline infusion, hypoaldosteronism.

State Winter's formula for the expected respiratory compensation in metabolic acidosis.

$$P_{CO_2}\ (\text{expected}) = 1.5 \times [\ce{HCO3^-}] + 8 \pm 2$$ If measured $P_{CO_2}$ is higher than predicted, there is a concurrent respiratory acidosis; if lower, a concurrent respiratory alkalosis.

Compare the three types of renal tubular acidosis (RTA) by defect, urine pH, and serum K+.

Type 1 (distal): impaired H+ secretion, urine pH > 5.5, hypokalemia, risk of stones. Type 2 (proximal): impaired $\ce{HCO3^-}$ reabsorption, urine pH variable (<5.5 when severe), hypokalemia. Type 4: aldosterone deficiency/resistance, urine pH < 5.5, hyperkalemia. All are normal-anion-gap acidoses.

Define nephrotic versus nephritic syndrome by their defining features.

Nephrotic: proteinuria $> 3.5$ g/day, hypoalbuminemia, edema, hyperlipidemia/lipiduria (podocyte injury). Nephritic: hematuria with dysmorphic RBCs/RBC casts, hypertension, oliguria, azotemia, and moderate (sub-nephrotic) proteinuria (glomerular inflammation).

What is the most common primary cause of nephrotic syndrome in children, and its key pathology and treatment?

Minimal change disease. Light microscopy is normal; electron microscopy shows diffuse podocyte foot-process effacement; no immune deposits. It is highly steroid-responsive (corticosteroids).

Describe IgA nephropathy (Berger disease) — the most common primary glomerulonephritis worldwide.

Mesangial deposition of IgA immune complexes. Classically presents with episodic gross hematuria 1–3 days after a mucosal (upper respiratory) infection ('synpharyngitic'). Immunofluorescence shows mesangial IgA. Related systemically to IgA vasculitis (Henoch-Schönlein purpura).

What are the two histologic patterns of primary focal segmental glomerulosclerosis (FSGS), and its clinical significance?

FSGS shows sclerosis affecting some glomeruli (focal) and only part of each affected tuft (segmental), with foot-process effacement on EM. It is a leading cause of nephrotic syndrome in adults (especially in Black patients, linked to APOL1 variants) and is often steroid-resistant, progressing to ESRD.

Which primary glomerulonephritis is classically post-infectious, and what are its serologic and biopsy findings?

Post-streptococcal (post-infectious) glomerulonephritis, ~1–3 weeks after group A strep pharyngitis or skin infection. Findings: low C3 complement, elevated ASO/anti-DNase B titers; biopsy shows enlarged hypercellular glomeruli with subepithelial 'humps' on EM and granular ('starry-sky') IgG/C3 on IF.

List the three classic causes of rapidly progressive (crescentic) glomerulonephritis by immunofluorescence pattern.

(1) Linear IF — anti-GBM disease (Goodpasture, with pulmonary hemorrhage). (2) Granular IF — immune-complex GN (lupus, post-infectious, IgA). (3) Pauci-immune (no deposits) — ANCA-associated vasculitis (GPA, MPA, EGPA). All show crescents on biopsy and cause rapid loss of renal function.

Describe diabetic nephropathy, the most common cause of secondary glomerular disease and ESRD.

Chronic hyperglycemia causes GBM thickening and mesangial expansion, with pathognomonic Kimmelstiel-Wilson nodules. It progresses from hyperfiltration → microalbuminuria → overt proteinuria → declining GFR. ACE inhibitors/ARBs and SGLT2 inhibitors slow progression.

How is lupus nephritis classified, and which class is most severe?

ISN/RPS classes I–VI: I minimal mesangial, II mesangial proliferative, III focal, IV diffuse proliferative, V membranous, VI advanced sclerosing. Class IV (diffuse proliferative) is the most common and most severe, often with 'wire-loop' lesions and full-house IF (IgG, IgM, IgA, C3, C1q).

What is the target antigen in primary membranous nephropathy, and its EM appearance?

The phospholipase A2 receptor (PLA2R) on podocytes is the target autoantigen in ~70–80% of primary cases. EM shows subepithelial immune-complex deposits with 'spike and dome' basement membrane projections; it is a leading cause of nephrotic syndrome in adults.

Define acute interstitial nephritis (AIN), its most common cause, and the classic clinical triad.

AIN is an immune-mediated inflammation of the renal interstitium causing acute kidney injury, most often drug-induced (NSAIDs, β-lactams/antibiotics, PPIs, diuretics). Classic triad (present in a minority): fever, rash, and eosinophilia; urinalysis may show sterile pyuria and white-cell casts, sometimes eosinophiluria.

How is acute interstitial nephritis managed?

Prompt discontinuation of the offending drug is the mainstay; most patients recover renal function. Corticosteroids may be used for severe or persistent cases (especially drug-induced or those not improving after withdrawal). Delayed treatment risks progression to chronic interstitial fibrosis.

What are common causes of chronic interstitial nephritis, and its urinary/imaging hallmarks?

Causes include analgesic nephropathy (chronic NSAID/phenacetin use, causing papillary necrosis), chronic lithium, lead/cadmium exposure, sarcoidosis, Sjögren, and obstructive/reflux nephropathy. Features: bland urine, tubular dysfunction (concentrating defect, tubular proteinuria), and small scarred kidneys with progressive CKD.

Distinguish benign from malignant (accelerated) hypertensive nephrosclerosis pathologically.

Benign nephrosclerosis: hyaline arteriolosclerosis and fibroelastic intimal thickening with a finely granular ('grain-leather') cortical surface. Malignant nephrosclerosis: fibrinoid necrosis and hyperplastic 'onion-skin' arteriolitis producing flea-bitten petechial cortex, seen with severe/accelerated hypertension and acute renal failure.

What are the two main pathologies causing renal artery stenosis and their typical patient demographics?

(1) Atherosclerosis (~90%) — older patients, ostial/proximal lesions, cardiovascular risk factors. (2) Fibromuscular dysplasia — younger women, 'string-of-beads' appearance of the mid-to-distal artery. Both cause renovascular hypertension via RAAS activation.

Why can starting an ACE inhibitor precipitate acute kidney injury in bilateral renal artery stenosis?

In severe stenosis, GFR is maintained by angiotensin II-mediated efferent arteriolar constriction. ACE inhibitors/ARBs block this, dropping glomerular filtration pressure and causing a sharp rise in creatinine/AKI (especially with bilateral stenosis or a stenotic solitary kidney).

Define thrombotic microangiopathy (TMA) and its characteristic laboratory triad.

TMA is endothelial injury causing microvascular platelet thrombi. Triad: microangiopathic hemolytic anemia (schistocytes, elevated LDH, low haptoglobin), thrombocytopenia, and organ (often renal) injury. The Coombs test is negative. Umbrella includes HUS and TTP.

Contrast typical HUS, TTP, and atypical HUS in pathophysiology.

Typical HUS: Shiga toxin (E. coli O157:H7) after bloody diarrhea, predominantly renal, most common in children. TTP: severe ADAMTS13 deficiency → large vWF multimers → more neurologic involvement, fever; treat with plasma exchange. Atypical HUS: uncontrolled alternative complement activation; treated with eculizumab (anti-C5).

What is the principle of hemodialysis and the physical processes it uses?

Blood is passed across a semipermeable membrane against dialysate flowing countercurrent. Solute removal is by diffusion (down concentration gradients) and convection; fluid removal is by ultrafiltration driven by a transmembrane pressure gradient. It clears small solutes (urea, K+) and corrects acid-base/volume.

What is the preferred long-term vascular access for hemodialysis, and why over alternatives?

A native arteriovenous (AV) fistula is preferred — lowest rates of infection and thrombosis and greatest longevity, though it requires weeks to mature. AV grafts are next; tunneled central venous catheters have the highest infection and thrombosis risk and are least preferred.

How does peritoneal dialysis work, and name its most important infectious complication.

Dialysate is instilled into the peritoneal cavity; the peritoneal membrane acts as the semipermeable surface for diffusion of solutes, while an osmotic agent (glucose/icodextrin) drives ultrafiltration of water. The major complication is peritonitis (cloudy effluent, abdominal pain), typically from gram-positive skin flora.

What is the preferred donor source and the main immunologic barrier in kidney transplantation, and the classic maintenance immunosuppression regimen?

Living-donor kidneys have the best graft and patient survival. HLA matching (and ABO compatibility) plus a negative crossmatch minimize rejection. Standard maintenance triple therapy: a calcineurin inhibitor (tacrolimus), an antimetabolite (mycophenolate), and corticosteroids (prednisone).

Differentiate hyperacute, acute, and chronic kidney transplant rejection.

Hyperacute: minutes–hours, preformed anti-donor antibodies → thrombosis, requires immediate graft removal. Acute: days–months, cellular (T-cell) and/or antibody-mediated → treated with steroids/antibody therapy. Chronic: months–years, progressive interstitial fibrosis/tubular atrophy and vasculopathy → gradual, largely irreversible graft loss.

Describe autosomal dominant polycystic kidney disease (ADPKD): genetics, key renal features, and extrarenal manifestations.

Mutations in PKD1 (chromosome 16, ~85%, more severe) or PKD2 (chromosome 4). Bilateral enlarging renal cysts cause hypertension, hematuria, flank pain, stones, and progression to ESRD by middle age. Extrarenal: hepatic cysts, berry (intracranial) aneurysms, mitral valve prolapse, and colonic diverticula.

Contrast autosomal recessive (ARPKD) with autosomal dominant polycystic kidney disease.

ARPKD (PKHD1 gene, fibrocystin) presents in infancy/childhood with bilateral enlarged kidneys and dilated collecting ducts, often with oligohydramnios/Potter sequence and congenital hepatic fibrosis (portal hypertension). ADPKD presents in adulthood with dominant inheritance, PKD1/PKD2 mutations, and berry aneurysm/hepatic cyst associations.