Nephron Study Guide

📖 Core Concepts Nephron – the kidney’s microscopic functional unit; composed of a renal corpuscle (glomerulus + Bowman’s capsule) and a renal tubule. Filtration (ultrafiltration) – passive passage of plasma through the glomerular capillary wall into Bowman’s space, driven by hydrostatic pressure; proteins and cells stay in the blood. Reabsorption – movement of water and solutes from tubular fluid back into peritubular capillaries; can be passive (diffusion) or active (ATP‑driven pumps). Secretion – active transport of substances from peritubular capillaries into the tubular lumen. Counter‑current multiplication – the loop of Henle creates a hyperosmotic medullary interstitium, allowing the collecting duct to reabsorb water under ADH influence. Juxtaglomerular Apparatus (JGA) – sensor‑secretory complex (macula densa, juxtaglomerular cells, extraglomerular mesangial cells) that regulates renin release and thus the renin‑angiotensin‑aldosterone system (RAAS). Hormonal regulators – ADH (water permeability), aldosterone (Na⁺ reabsorption / K⁺ secretion), atrial natriuretic peptide (ANP; Na⁺ secretion), parathyroid hormone (PTH; Ca²⁺ reabsorption, phosphate secretion). --- 📌 Must Remember Nephron count: 1–1.5 million per kidney. Filtration fraction: 20 % of plasma is filtered; 80 % continues in peritubular capillaries. Proximal tubule reabsorption: ≈80 % of filtered glucose, >50 % of filtered Na⁺, most water, and all amino acids. Loop of Henle: Descending limb – water‑permeable, solute‑impermeable. Thin ascending limb – solute‑permeable, water‑impermeable. Thick ascending limb – actively pumps Na⁺ (and Cl⁻), water‑impermeable → creates medullary hypertonicity. Collecting duct water reabsorption: up to 75 % when ADH is present. Hormone actions: Aldosterone → ↑ Na⁺ reabsorption, ↑ K⁺ secretion (distal tubule & collecting duct). ANP → ↑ Na⁺ secretion (distal tubule). PTH → ↑ Ca²⁺ reabsorption, ↑ phosphate secretion (distal tubule). Juxtaglomerular cells release renin → angiotensin I → angiotensin II → vasoconstriction + aldosterone release. --- 🔄 Key Processes Glomerular Filtration Blood enters glomerulus via afferent arteriole → high hydrostatic pressure (efferent arteriole narrower) → plasma forced through three filtration barriers → filtrate in Bowman’s space. Proximal Tubule Reabsorption Brush‑border microvilli ↑ surface area. Na⁺/glucose co‑transporters (SGLT) reclaim glucose & Na⁺; water follows osmotically. Majority of filtered Na⁺, water, amino acids, bicarbonate reabsorbed. Loop of Henle Counter‑Current Multiplication Descending limb: water exits (aquaporins) → filtrate becomes hypo‑osmotic. Thin ascending limb: NaCl diffuses out → interstitium gradually concentrates. Thick ascending limb: Na⁺ actively pumped out (NKCC2) → further raises interstitial osmolality; impermeable to water. Distal Tubule & Collecting Duct Regulation Aldosterone binds receptors → ↑ Na⁺ channels (ENaC) & Na⁺/K⁺‑ATPase → Na⁺ reabsorption, K⁺ secretion. ADH → V2 receptors → cAMP → insertion of aquaporin‑2 → water reabsorption. ANP → cGMP → inhibits Na⁺ reabsorption. Secretion (e.g., K⁺, H⁺, drugs) Active transporters in distal tubule/collecting duct move waste into lumen for excretion. --- 🔍 Key Comparisons Cortical vs. Juxtamedullary Nephrons Loop length: short vs. long (deep medulla). Proportion: majority cortical; 15 % juxtamedullary. Function: juxtamedullary create the medullary osmotic gradient (critical for water reabsorption). Descending vs. Ascending Limb of Loop of Henle Permeability: descending – water‑permeable, solute‑impermeable; ascending – water‑impermeable, solute‑permeable (thin) or actively transports Na⁺ (thick). Aldosterone vs. ANP Aldosterone → ↑ Na⁺ reabsorption, ↓ Na⁺ excretion; ANP → ↑ Na⁺ excretion, ↓ Na⁺ reabsorption. PTH vs. Aldosterone (on distal tubule) PTH → ↑ Ca²⁺ reabsorption, ↑ phosphate secretion. Aldosterone → ↑ Na⁺ reabsorption, ↑ K⁺ secretion. --- ⚠️ Common Misunderstandings “All filtered glucose is reabsorbed” – true only when plasma glucose ≤ renal threshold; excess appears in urine (glycosuria). “Loop of Henle only reabsorbs water” – the thick ascending limb actively reabsorbs Na⁺/Cl⁻, generating the gradient; water reabsorption occurs later in the collecting duct under ADH. “ADH acts on the proximal tubule” – ADH’s primary effect is on the collecting duct; the proximal tubule is already maximally permeable to water. “Renin is released by the glomerulus” – renin comes from juxtaglomerular cells (specialized smooth‑muscle cells) in the afferent arteriole, not from the glomerulus itself. --- 🧠 Mental Models / Intuition “Sieve + Pipe” – Think of the glomerulus as a sieve (filters plasma) and the tubule as a pipe with selective “valves” (transporters) that add back what the body needs. “Thermos Flask” – The loop of Henle is a thermos: the thick ascending limb “heats” (adds solutes) to the medulla, while the descending limb “cools” (loses water), establishing a temperature (osmotic) gradient. “Hormone Switchboard” – Aldosterone = “Na⁺‑ON, K⁺‑OFF”; ANP = “Na⁺‑OFF”; ADH = “Water‑ON”. Remember the on/off pattern to decide net direction of reabsorption. --- 🚩 Exceptions & Edge Cases High‑protein diet → increased urea reabsorption in the inner medullary collecting duct, enhancing medullary osmolality. Chronic kidney disease – nephron loss ≈50 % early in disease, mimicking normal aging; remaining nephrons undergo hyperfiltration. Diuretics – loop diuretics block NKCC2 in thick ascending limb, collapsing the medullary gradient → massive diuresis. --- 📍 When to Use Which Identify the segment → look at the transport property: Water‑permeable, no solute transport → descending limb. Active Na⁺ pump, water‑impermeable → thick ascending limb. Brush‑border, bulk reabsorption → proximal tubule. Hormonal influence → ADH present → expect water reabsorption in collecting duct. Aldosterone elevated → anticipate increased Na⁺ reabsorption & K⁺ secretion in distal nephron. ANP elevated → expect reduced Na⁺ reabsorption (natriuresis). --- 👀 Patterns to Recognize “20 % filtration, 80 % reabsorption” – most of the filtered load is reclaimed before the loop of Henle. “Long loop = strong gradient” – juxtamedullary nephrons (long loops) are the primary drivers of the medullary hyperosmolarity. “Hormone‑driven segment specificity” – ADH → collecting duct; Aldosterone → distal tubule & collecting duct; PTH → distal tubule. “Counter‑current flow” – parallel, opposite‑direction flow in descending vs. ascending limbs; essential for multiplication. --- 🗂️ Exam Traps Choosing the wrong limb for water transport – many students pick the ascending limb; remember only the descending limb is water‑permeable. Confusing aldosterone with ADH – aldosterone affects Na⁺/K⁺, not water permeability; ADH controls water channels. Assuming all nephrons have the same loop length – cortical nephrons have short loops; juxtamedullary have long loops (critical for concentrating urine). Renin source misidentification – renin comes from juxtaglomerular cells, not from the glomerulus itself. “All filtered solutes are reabsorbed” – glucose has a threshold; phosphate, urea, and creatinine are partially secreted. ---