USMLE Step 1 - High-Yield Renal Pathophysiology & Acid-Base Disorders Flashcards

Question 1

How is Glomerular Filtration Rate (GFR) calculated using clearance, and why is Inulin clearance the gold standard?

Accepted Answer

Inulin is freely filtered and neither reabsorbed nor secreted, so $GFR = C_{inulin} = \frac{U_{inulin} 	imes V}{P_{inulin}}$. Clinically, **creatinine clearance** is used to estimate GFR, though it slightly overestimates GFR due to mild tubular secretion.

Question 2

What equations determine Effective Renal Plasma Flow (eRPF) and Total Renal Blood Flow (RBF)?

Accepted Answer

$eRPF = C_{PAH} = \frac{U_{PAH} 	imes V}{P_{PAH}}$. Total $RBF = \frac{RPF}{1 - 	ext{Hematocrit}}$. PAH clearance underestimates true RPF by ~10% because PAH is not 100% extracted in a single pass.

Question 3

Define Filtration Fraction (FF) and describe how Angiotensin II alters GFR, RPF, and FF.

Accepted Answer

$FF = \frac{GFR}{RPF}$ (Normal ~20%). **Angiotensin II** preferentially constricts the *efferent arteriole*, which increases GFR and decreases RPF, resulting in a **significantly increased FF** ($\uparrow FF$).

Question 4

How is the Serum Anion Gap calculated, and what threshold defines a High Anion Gap Metabolic Acidosis (HAGMA)?

Accepted Answer

$	ext{Anion Gap} = [Na^+] - ([Cl^-] + [HCO_3^-])$. Normal range is **8–12 mEq/L**. Anion gap $> 12 	ext{ mEq/L}$ indicates HAGMA due to the accumulation of unmeasured organic anions consuming bicarbonate.

Question 5

What are the primary etiologies of High Anion Gap Metabolic Acidosis (MUDPILES)?

Accepted Answer

Mnemonic **MUDPILES**:
- **M**ethanol
- **U**remia
- **D**KA
- **P**ropylene glycol / Paracetamol
- **I**soniazid / Iron
- **L**actic acidosis
- **E**thylene glycol
- **S**alicyates (late)

Question 6

What is Winter's Formula, and how is it used to evaluate respiratory compensation in metabolic acidosis?

Accepted Answer

Predicts expected arterial $P_{CO_2}$: $	ext{Expected } P_{CO_2} = 1.5 	imes [HCO_3^-] + 8 \pm 2$.
- If actual $P_{CO_2} > 	ext{expected}$: Concomitant **respiratory acidosis**.
- If actual $P_{CO_2} < 	ext{expected}$: Concomitant **respiratory alkalosis**.

Question 7

Compare urine pH and potassium levels in Renal Tubular Acidosis (RTA) Types 1, 2, and 4.

Accepted Answer

- **Type 1 (Distal)**: Distal $H^+$ secretion defect. Urine $pH > 5.5$. **Hypokalemia**. Associated with kidney stones.
- **Type 2 (Proximal)**: Proximal $HCO_3^-$ reabsorption defect. Urine $pH < 5.5$ (eventually). **Hypokalemia**.
- **Type 4 (Hyperkalemic)**: Hypoaldosteronism or aldosterone resistance. Urine $pH < 5.5$. **Hyperkalemia**.

Question 8

What key clinical and lab features distinguish Nephrotic Syndrome from Nephritic Syndrome?

Accepted Answer

- **Nephrotic**: Massive proteinuria ($>3.5 	ext{ g/day}$), hypoalbuminemia, generalized edema, hyperlipidemia, and fatty casts ("Maltese cross").
- **Nephritic**: Hematuria (dysmorphic RBCs, RBC casts), hypertension, oliguria, azotemia, and mild-to-moderate proteinuria ($<3.5 	ext{ g/day}$).

Question 9

What light and electron microscopy findings characterize Minimal Change Disease (MCD)?

Accepted Answer

- **Light Microscopy**: Normal glomeruli.
- **Electron Microscopy**: Effacement (flattening) of **podocyte foot processes**.
- **Clinical**: Most common nephrotic syndrome in children; selective albuminuria; highly responsive to **corticosteroids**.

Question 10

What immunofluorescence (IF) and electron microscopy (EM) pattern is diagnostic for Membranous Nephropathy?

Accepted Answer

- **EM**: **"Spike and dome"** appearance with subepithelial immune complex deposits.
- **IF**: Granular IgG and C3 deposition along the basement membrane.
- **Etiology**: Idiopathic (anti-PLA2R antibodies), drugs (NSAIDs), HBV/HCV, or solid malignancies.

Question 11

What are the risk factors, demographics, and light microscopy findings in Focal Segmental Glomerulosclerosis (FSGS)?

Accepted Answer

- **Demographics/Risk**: Most common in **African Americans and Hispanics**; associated with **HIV**, heroin use, sickle cell disease, and massive obesity.
- **LM**: Focal and segmental sclerosis with hyalinosis.
- **Outcome**: Poor response to steroids; frequently progresses to end-stage renal disease (ESRD).

Question 12

Describe the classic triad, complement levels, and electron microscopy findings in Post-Streptococcal Glomerulonephritis (PSGN).

Accepted Answer

- **Presentation**: Hematuria (tea-colored urine), hypertension, periorbital edema 1–4 weeks post-GAS infection.
- **Labs**: Low serum $C3$.
- **EM**: Large **subepithelial "humps"** (immune complex deposits).
- **IF**: Starry sky granular pattern ($IgG, IgM, C3$).

Question 13

What pathognomonic lesion is seen on light microscopy in Rapidly Progressive Glomerulonephritis (RPGN), and what composes it?

Accepted Answer

Characterized by **crescents** in Bowman's space on light microscopy. Crescents consist of **fibrin**, **macrophages**, and proliferating parietal epithelial cells. RPGN rapidly leads to renal failure within days to weeks.

Question 14

How do timing and complement levels differentiate IgA Nephropathy (Berger Disease) from PSGN?

Accepted Answer

- **IgA Nephropathy**: Recurrent gross hematuria occurring **concurrently or within 1–3 days** of an upper respiratory or GI infection ("synpharyngitic"). $C3$ levels are **normal**.
- **PSGN**: Hematuria develops **1–4 weeks** after a streptococcal infection. $C3$ levels are **decreased**.

Question 15

What is the genetic defect, clinical triad, and renal EM finding in Alport Syndrome?

Accepted Answer

- **Genetics**: X-linked dominant mutation in **Type IV collagen** ($\alpha-5$ chain).
- **Triad**: Sensorineural hearing loss, ocular abnormalities (anterior lenticonus), and progressive hematuria/nephropathy.
- **EM**: Irregular thinning and thickening of GBM with a **"basket-weave"** appearance.

Question 16

Where do Loop Diuretics act, what is their molecular mechanism, and what electrolyte abnormalities do they cause?

Accepted Answer

- **Site**: Thick ascending limb (TAL) of Henle's loop.
- **Mechanism**: Inhibits the $Na^+/K^+/2Cl^-$ (NKCC2) cotransporter, disrupting the corticomedullary osmotic gradient.
- **Electrolytes**: Hypokalemic metabolic alkalosis, hypomagnesemia, and **hypocalcemia** ("Loops Lose $Ca^{2+}$"). Also causes ototoxicity.

Question 17

What is the site of action, mechanism, and electrolyte profile of Thiazide Diuretics?

Accepted Answer

- **Site**: Early Distal Convoluted Tubule (DCT).
- **Mechanism**: Inhibits the $Na^+/Cl^-$ (NCC) cotransporter.
- **Electrolytes**: Hypokalemic metabolic alkalosis, hyponatremia, **hypercalcemia** (increases $Ca^{2+}$ reabsorption), and **hyperuricemia** (can precipitate gout).

Question 18

Differentiate the mechanisms of action between Spironolactone and Amiloride in the collecting tubule.

Accepted Answer

- **Spironolactone / Eplerenone**: Competitive antagonists at the **mineralocorticoid (aldosterone) receptor**; decrease $Na^+$ channel and $Na^+/K^+$ ATPase synthesis.
- **Amiloride / Triamterene**: Directly block Epithelial Sodium Channels (**ENaC**).
- **Both**: Cause hyperkalemia and hyperchloremic metabolic acidosis.

Question 19

How do ACE Inhibitors impact renal hemodynamics, and why are they contraindicated in bilateral renal artery stenosis?

Accepted Answer

ACE inhibitors block Angiotensin II, causing **preferential vasodilation of the efferent arteriole**. This decreases intraglomerular hydrostatic pressure and drops GFR. In bilateral renal artery stenosis, GFR is dependent on efferent constriction; ACEi use leads to **acute renal failure** ($\uparrow 	ext{creatinine} > 30\%$).

Question 20

Match Bartter, Gitelman, and Liddle syndromes to their diuretic equivalents or mutated transporters.

Accepted Answer

- **Bartter Syndrome**: AR defect in NKCC2 in TAL. Mimics **loop diuretic** overuse (hypokalemia, metabolic alkalosis, $\uparrow U_{Ca}$).
- **Gitelman Syndrome**: AR defect in NCC in DCT. Mimics **thiazide diuretic** overuse (hypokalemia, metabolic alkalosis, $\downarrow U_{Ca}$, hypomagnesemia).
- **Liddle Syndrome**: AD gain-of-function mutation causing $\uparrow$ **ENaC** activity. Mimics **hyperaldosteronism**, but with **low renin and low aldosterone**.

USMLE Step 1 - High-Yield Renal Pathophysiology & Acid-Base Disorders

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