Free MCAT study guide — Biological and Biochemical Foundations of Living Systems
Renal physiology is a high-yield MCAT topic that integrates biology, chemistry, and physics. The kidneys filter approximately 180 liters of plasma daily, but only excrete 1-2 liters of urine, demonstrating the efficiency of tubular reabsorption. You must understand the structure and function of the nephron: the glomerulus and Bowman's capsule (filtration), proximal convoluted tubule (bulk reabsorption), loop of Henle (countercurrent multiplier system), distal convoluted tubule (fine-tuning under hormonal control), and collecting duct (final concentration under ADH control). Key concepts include glomerular filtration rate (GFR) and the Starling forces that drive filtration, the countercurrent multiplier and exchanger systems that establish the medullary osmotic gradient, and the hormonal regulation of kidney function by aldosterone, ADH (vasopressin), atrial natriuretic peptide (ANP), and parathyroid hormone (PTH). You should also understand acid-base balance, including how the kidneys regulate blood pH through bicarbonate reabsorption and hydrogen ion secretion, and how to interpret arterial blood gas values to distinguish respiratory from metabolic acidosis or alkalosis.
Each kidney contains approximately one million nephrons, the functional units of the kidney. Blood enters the glomerulus (a capillary tuft) via the afferent arteriole and exits via the efferent arteriole. The glomerular filtration barrier consists of three layers: fenestrated capillary endothelium, basement membrane (negatively charged, repels proteins), and podocyte foot processes (filtration slits). Filtration is driven by Starling forces: glomerular hydrostatic pressure (favors filtration, approximately 55 mmHg) minus Bowman's capsule hydrostatic pressure (opposes, approximately 15 mmHg) and glomerular oncotic pressure (opposes, approximately 30 mmHg). Net filtration pressure is approximately 10 mmHg. GFR is normally about 125 mL/min or 180 L/day. The filtrate contains water, electrolytes, glucose, amino acids, and small molecules but NOT proteins or blood cells. GFR is regulated by myogenic autoregulation, tubuloglomerular feedback (macula densa sensing NaCl delivery), and sympathetic nervous system input.
The PCT reabsorbs approximately 65% of filtered sodium, water, and solutes. The apical membrane contains sodium-glucose cotransporters (SGLT2), sodium-amino acid cotransporters, and sodium-hydrogen exchangers (NHE3). The basolateral Na+/K+ ATPase maintains the sodium gradient driving all these transporters. Glucose reabsorption has a transport maximum (Tm): when plasma glucose exceeds approximately 180 mg/dL (the renal threshold), glucose appears in the urine (glucosuria), as occurs in uncontrolled diabetes. Water follows solute reabsorption osmotically (obligatory water reabsorption). The PCT also reabsorbs all filtered bicarbonate (via carbonic anhydrase on the apical surface) and secretes organic acids, drugs (such as penicillin), and hydrogen ions. PAH (para-aminohippuric acid) is both filtered and secreted, making it useful for measuring renal plasma flow. The filtrate leaving the PCT is isosmotic to plasma (approximately 300 mOsm/L).
The loop of Henle establishes the medullary osmotic gradient essential for urine concentration. The thin descending limb is permeable to water but not to solutes, so water leaves osmotically as the tubule descends into the hyperosmotic medulla, concentrating the filtrate. At the hairpin turn, osmolarity reaches approximately 1200 mOsm/L in juxtamedullary nephrons. The thick ascending limb is impermeable to water and actively transports NaCl out via the NKCC2 (Na-K-2Cl) cotransporter on the apical membrane. This makes the filtrate dilute (approximately 100 mOsm/L) as it exits the ascending limb, while the medullary interstitium becomes hypertonic. Loop diuretics (furosemide) inhibit NKCC2, preventing the formation of the medullary gradient and reducing the kidney's ability to concentrate urine. The vasa recta (peritubular capillaries around the loop) act as countercurrent exchangers, preserving the medullary gradient by equilibrating with the interstitium passively without washing it out.
The distal convoluted tubule (DCT) is the site of fine-tuned regulation. Aldosterone (from the adrenal cortex, stimulated by angiotensin II and hyperkalemia) acts on principal cells to increase sodium reabsorption and potassium secretion via ENaC and ROMK channels. Aldosterone also increases Na+/K+ ATPase expression. ADH (vasopressin, from the posterior pituitary) acts on the collecting duct to insert aquaporin-2 channels, increasing water reabsorption and producing concentrated urine. Without ADH (as in diabetes insipidus), the collecting duct is impermeable to water, and large volumes of dilute urine are produced. PTH acts on the DCT to increase calcium reabsorption. Atrial natriuretic peptide (ANP), released by atrial myocytes in response to volume expansion, inhibits sodium reabsorption and aldosterone secretion, promoting natriuresis and diuresis. The RAAS system: renin (from juxtaglomerular cells) converts angiotensinogen to angiotensin I, which is converted to angiotensin II by ACE in the lungs. Angiotensin II vasoconstricts and stimulates aldosterone release.
The kidneys regulate acid-base balance by reabsorbing filtered bicarbonate (mainly in the PCT), secreting hydrogen ions (via H+ ATPase and H+/K+ ATPase in intercalated cells), and generating new bicarbonate through the excretion of ammonium (NH4+) and titratable acids (H2PO4-). Metabolic acidosis (low blood pH, low bicarbonate) can result from diabetic ketoacidosis, lactic acidosis, or diarrhea (loss of bicarbonate). The respiratory compensation is hyperventilation (blowing off CO2, Kussmaul breathing). Metabolic alkalosis (high pH, high bicarbonate) results from vomiting (loss of HCl) or excessive aldosterone. Respiratory acidosis (high CO2, low pH) results from hypoventilation (COPD, respiratory depression). Respiratory alkalosis (low CO2, high pH) results from hyperventilation (anxiety, high altitude). The Henderson-Hasselbalch equation (pH = pKa + log[HCO3-]/[CO2]) is used to understand the relationship between these variables. Normal arterial blood: pH 7.40, pCO2 40 mmHg, HCO3- 24 mEq/L.
Renal clearance is the volume of plasma completely cleared of a substance per unit time. Clearance = (Ux * V) / Px, where Ux is urine concentration, V is urine flow rate, and Px is plasma concentration. Inulin clearance equals GFR because inulin is freely filtered, not reabsorbed, and not secreted. Creatinine clearance is used clinically as an approximation of GFR. If a substance's clearance is less than inulin, it is being reabsorbed (e.g., glucose, amino acids, water). If clearance is greater than inulin, it is being secreted (e.g., PAH). PAH clearance approximates renal plasma flow (RPF) because PAH is nearly completely removed from plasma in one pass through the kidney. The filtration fraction (FF) = GFR/RPF, normally about 20%. Understanding these calculations is essential for MCAT quantitative reasoning in passage-based questions.
GFR is approximately 125 mL/min or 180 L/day; only 1-2 L of urine is produced daily.
The PCT reabsorbs 65% of filtered sodium and water, and all glucose and amino acids.
The descending limb of the loop of Henle is permeable to water; the ascending limb is impermeable to water.
The thick ascending limb uses NKCC2 to actively transport NaCl, diluting the filtrate.
Aldosterone increases Na+ reabsorption and K+ secretion in the collecting duct.
ADH inserts aquaporin-2 in the collecting duct to reabsorb water.
Diabetes insipidus: lack of ADH or resistance to ADH causes dilute urine and polyuria.
RAAS: renin -> angiotensin I -> (ACE) -> angiotensin II -> aldosterone + vasoconstriction.
ACE inhibitors treat hypertension by blocking angiotensin II production.
Inulin clearance = GFR (gold standard); creatinine clearance approximates GFR clinically.
PAH clearance approximates renal plasma flow (RPF).
Filtration fraction = GFR / RPF, normally about 20%.
The juxtaglomerular apparatus contains macula densa cells (sense NaCl) and juxtaglomerular cells (secrete renin).
Loop diuretics (furosemide) inhibit NKCC2; thiazide diuretics inhibit NCC in the DCT.
Confusing the descending limb (permeable to water, concentrates filtrate) with the ascending limb (impermeable to water, dilutes filtrate).
Forgetting that the afferent arteriole brings blood TO the glomerulus and the efferent arteriole takes blood AWAY.
Mixing up aldosterone (Na+ reabsorption, K+ secretion) with ADH (water reabsorption only).
Assuming glucose always appears in urine -- it only appears when plasma glucose exceeds the renal threshold (about 180 mg/dL).
Confusing renal clearance with excretion rate -- clearance is volume of plasma cleared, not amount excreted.
Forgetting that respiratory compensation for metabolic acidosis is hyperventilation (decreased CO2), not hypoventilation.
Mixing up the primary disturbance with the compensation in acid-base problems.
Practice tracing a molecule of water or sodium through the entire nephron, noting what happens at each segment. Draw a diagram of the nephron and label each segment with its permeabilities, transporters, and hormonal regulation. The MCAT frequently presents scenarios where a hormone is elevated or a transporter is inhibited and asks you to predict the effect on urine composition and volume.
Work through clearance calculations: given urine concentration, urine flow rate, and plasma concentration, calculate clearance and determine whether a substance is reabsorbed or secreted relative to inulin. Practice acid-base problems by identifying the primary disturbance (look at pH first, then CO2 and HCO3-) and predicting the compensatory response. Use the mnemonic: metabolic problems have respiratory compensation and vice versa.
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