USMLE Step 1 - Renal Physiology & Acid-Base Disorders

To filter blood, forming an ultrafiltrate that is largely protein-free and cell-free, based on size and charge.

GFR is the volume of plasma filtered per unit time. It's determined by the net filtration pressure (hydrostatic and oncotic pressures across the glomerular capillary) and the hydraulic permeability and surface area of the glomerular capillaries ($K_f$). Factors include glomerular hydrostatic pressure, Bowman's capsule hydrostatic pressure, and glomerular capillary oncotic pressure.

Renal clearance is the volume of plasma completely cleared of a substance per unit time. The formula is $C=\frac{U\times V}{P}$, where $U$ is the urine concentration of the substance, $V$ is the urine flow rate, and $P$ is the plasma concentration of the substance.

Inulin is the gold standard because it is freely filtered, not reabsorbed, and not secreted. Creatinine is commonly used clinically as an approximation, though it is slightly secreted, leading to a slight overestimation of GFR.

Para-aminohippuric acid (PAH) is used because it is freely filtered and actively secreted by the tubules, such that nearly all PAH entering the kidney is cleared from the plasma in a single pass. This allows for an accurate estimation of ERPF.

The PCT reabsorbs about 60-70% of filtered Na+, water, Cl-, K+, HCO3-, glucose, amino acids, and phosphate. Key transporters include SGLT2 (Na+/glucose cotransporter) and Na+/H+ exchanger. It also secretes organic acids and bases.

The TAL is crucial for creating the medullary osmotic gradient. It actively reabsorbs Na+, K+, and Cl- via the Na-K-2Cl cotransporter (NKCC2) but is impermeable to water, leading to dilution of the tubular fluid.

Carbonic Anhydrase Inhibitors (e.g., Acetazolamide) act primarily on the Proximal Convoluted Tubule (PCT). They inhibit carbonic anhydrase, reducing HCO3- reabsorption and Na+/H+ exchange, leading to increased HCO3- and Na+ excretion, and a metabolic acidosis.