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🫀Anatomy and Physiology II

Parts of the Nephron

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Why This Matters

The nephron is where the magic of kidney function actually happens—it's the structural and functional unit that transforms blood into urine through a carefully orchestrated sequence of filtration, reabsorption, and secretion. When you're tested on renal physiology, you're really being asked to demonstrate that you understand how each nephron segment contributes to homeostasis: maintaining fluid balance, regulating electrolytes, controlling blood pressure, and eliminating metabolic waste. These aren't isolated concepts—they connect directly to cardiovascular physiology, acid-base balance, and hormonal regulation.

Don't just memorize the parts in order like a shopping list. Instead, focus on what each structure does and why its unique features make that function possible. Ask yourself: Is this segment about filtering, reabsorbing, secreting, or regulating? What makes it permeable or impermeable? What hormones act here? When you can answer those questions, you'll nail both multiple-choice questions and FRQs that ask you to trace a molecule's journey or explain how the kidney responds to dehydration.


Filtration: Where It All Begins

The nephron's first job is to create filtrate from blood plasma. This happens in the renal corpuscle, where high pressure forces water and small solutes out of the blood while retaining cells and large proteins. The key principle here is pressure-driven bulk filtration across a selectively permeable barrier.

Renal Corpuscle (Bowman's Capsule and Glomerulus)

  • Glomerulus—a specialized capillary tuft where glomerular filtration occurs; fenestrated endothelium allows passage of water, ions, glucose, and small molecules while blocking blood cells and most proteins
  • Bowman's capsule—double-walled epithelial cup that surrounds the glomerulus and collects filtrate; the visceral layer contains podocytes with filtration slits
  • Filtration membrane—three-layer barrier (endothelium, basement membrane, podocytes) that determines what enters the tubular system; damage here causes proteinuria

Afferent Arteriole

  • Delivers blood to the glomerulus—its diameter directly controls how much blood enters for filtration
  • Regulates glomerular filtration rate (GFR)—vasodilation increases GFR, vasoconstriction decreases it; responds to sympathetic input and local signals
  • Autoregulation site—myogenic response and tubuloglomerular feedback maintain stable GFR despite blood pressure fluctuations

Efferent Arteriole

  • Carries filtered blood away from the glomerulus—smaller diameter than afferent arteriole helps maintain high glomerular pressure
  • Critical for GFR regulation—constriction increases glomerular pressure and filtration; targeted by angiotensin II during low blood pressure
  • Supplies downstream capillaries—branches into peritubular capillaries (cortical nephrons) or vasa recta (juxtamedullary nephrons)

Compare: Afferent vs. efferent arteriole—both regulate GFR, but afferent controls blood entering the glomerulus while efferent controls blood leaving. Constricting the afferent decreases GFR; constricting the efferent increases it. If an FRQ asks how angiotensin II maintains GFR during hypotension, efferent constriction is your answer.


Bulk Reabsorption: Reclaiming the Essentials

After filtration, the nephron must recover valuable substances before they're lost in urine. The proximal convoluted tubule handles the heavy lifting, reabsorbing most filtered water, sodium, glucose, and amino acids. This segment prioritizes quantity over fine-tuning—it's about getting back what the body can't afford to lose.

Proximal Convoluted Tubule (PCT)

  • Reabsorbs 65-70% of filtered water and sodium—uses Na⁺/K⁺-ATPase on the basolateral membrane to drive secondary active transport of glucose, amino acids, and other solutes
  • Brush border (microvilli)—dramatically increases surface area for absorption; loss of this border (as in acute tubular necrosis) severely impairs reabsorption
  • Secretes organic acids and bases—eliminates drugs, toxins, and metabolic waste like creatinine; important for drug clearance and clinical kidney function tests

Compare: PCT vs. DCT—both are convoluted tubules, but the PCT handles bulk reabsorption (~65-70% of filtrate) with extensive microvilli, while the DCT fine-tunes electrolytes under hormonal control with fewer microvilli. Think of PCT as "wholesale" and DCT as "retail."


Concentration Gradient: Creating the Osmotic Engine

The kidney's ability to produce concentrated urine depends entirely on the osmotic gradient in the renal medulla. The Loop of Henle and its parallel blood supply (vasa recta) work together through countercurrent mechanisms to establish and maintain this gradient. Without this system, you couldn't conserve water during dehydration.

Loop of Henle

  • Descending limb—permeable to water but not solutes; water leaves by osmosis as tubular fluid descends into the hypertonic medulla, concentrating the filtrate
  • Ascending limb—impermeable to water; actively transports Na⁺, K⁺, and Cl⁻ out via NKCC2 transporters (thick segment), diluting the tubular fluid while adding solutes to the medullary interstitium
  • Countercurrent multiplier—the opposing flow directions and different permeabilities create a progressively concentrated medulla (up to 1200 mOsm/L at the papilla); essential for producing concentrated urine

Vasa Recta

  • Specialized capillaries paralleling the Loop of Henle—found only in juxtamedullary nephrons; supply oxygen and nutrients to the medulla without washing away the osmotic gradient
  • Countercurrent exchanger—blood flowing down gains solutes and loses water; blood flowing up loses solutes and gains water; passive process that preserves medullary hypertonicity
  • Clinical relevance—damage to vasa recta impairs urine concentrating ability; explains why medullary ischemia causes concentrating defects

Compare: Countercurrent multiplier (Loop of Henle) vs. countercurrent exchanger (vasa recta)—the Loop creates the medullary gradient through active transport, while the vasa recta preserves it through passive exchange. Both require parallel, opposite-flow arrangements, but one is active and one is passive.


Fine-Tuning: Hormonal Control of Final Composition

The distal nephron segments—DCT and collecting duct—make final adjustments to urine composition based on the body's current needs. These segments respond to hormones like aldosterone, ADH, and parathyroid hormone to precisely regulate electrolyte and water balance. This is where homeostatic feedback loops meet nephron anatomy.

Distal Convoluted Tubule (DCT)

  • Hormone-regulated reabsorptionaldosterone increases Na⁺ reabsorption (and K⁺ secretion); parathyroid hormone increases Ca²⁺ reabsorption
  • Secretes K⁺ and H⁺—principal cells handle potassium; intercalated cells manage acid-base balance by secreting H⁺ or reabsorbing bicarbonate
  • Contains macula densa cells—specialized epithelial cells that sense tubular Na⁺/Cl⁻ concentration and signal to the juxtaglomerular apparatus; part of tubuloglomerular feedback

Collecting Duct

  • Final water reabsorption siteADH (antidiuretic hormone) inserts aquaporin-2 channels, making the duct permeable to water; without ADH, dilute urine is produced
  • Urea recycling—reabsorbs urea in the inner medullary portion, contributing ~50% of the medullary osmotic gradient; regulated by ADH
  • Convergence point—multiple nephrons drain into each collecting duct, which merges into the renal pelvis; final opportunity to modify urine before excretion

Compare: DCT vs. collecting duct—both respond to hormones, but DCT primarily handles electrolytes (aldosterone, PTH) while the collecting duct primarily handles water (ADH). An FRQ about dehydration response should focus on ADH and the collecting duct; one about hyperkalemia should focus on aldosterone and the DCT.


Vascular Support: Reabsorption and Secretion Partners

The peritubular capillaries form a low-pressure network that receives everything the tubules reabsorb and delivers substances for secretion. These capillaries complete the circuit—without them, reabsorbed materials would have nowhere to go.

Peritubular Capillaries

  • Surround cortical nephron tubules—arise from efferent arterioles; low hydrostatic pressure and high oncotic pressure favor reabsorption from interstitial fluid
  • Reabsorption highway—water, glucose, amino acids, Na⁺, and other reabsorbed substances enter here to return to systemic circulation
  • Secretion source—deliver waste products (H⁺, K⁺, drugs, creatinine) to tubular cells for secretion into the filtrate

Compare: Peritubular capillaries vs. vasa recta—both are post-glomerular capillaries, but peritubular capillaries serve cortical nephrons and handle general reabsorption/secretion, while vasa recta serve juxtamedullary nephrons and specifically preserve the medullary gradient. Location determines function.


Regulation: The Nephron's Control Center

The juxtaglomerular apparatus acts as a sensor-effector unit that monitors filtrate composition and blood pressure, then adjusts nephron function accordingly. This structure integrates local feedback with systemic hormonal control.

Juxtaglomerular Apparatus (JGA)

  • Location—where the DCT contacts the afferent arteriole; includes juxtaglomerular (JG) cells, macula densa, and extraglomerular mesangial cells
  • Renin release—JG cells (modified smooth muscle in afferent arteriole wall) secrete renin when blood pressure drops or macula densa senses low Na⁺/Cl⁻; initiates the renin-angiotensin-aldosterone system (RAAS)
  • Tubuloglomerular feedback—macula densa cells detect high NaCl in filtrate (indicating high GFR) and signal afferent arteriole constriction to reduce GFR; local autoregulation independent of systemic hormones

Compare: JGA vs. baroreceptors—both sense pressure changes, but the JGA monitors renal perfusion and responds by releasing renin (hormonal), while arterial baroreceptors monitor systemic pressure and respond via autonomic reflexes (neural). The JGA provides slower, sustained regulation; baroreceptors provide rapid adjustments.


Quick Reference Table

ConceptBest Examples
FiltrationGlomerulus, Bowman's capsule, afferent/efferent arterioles
Bulk reabsorptionProximal convoluted tubule
Concentration gradientLoop of Henle (descending/ascending), vasa recta
Hormonal fine-tuningDistal convoluted tubule, collecting duct
Water balance (ADH)Collecting duct
Electrolyte regulation (aldosterone)DCT, collecting duct
Countercurrent mechanismsLoop of Henle (multiplier), vasa recta (exchanger)
GFR regulationAfferent arteriole, efferent arteriole, JGA

Self-Check Questions

  1. Which two nephron segments are impermeable to water, and how does this impermeability serve different functions in each?

  2. A patient has low ADH levels. Which nephron structure will be most affected, and what will happen to urine concentration?

  3. Compare the roles of the afferent and efferent arterioles in regulating GFR. How would constricting each one differently affect filtration?

  4. The Loop of Henle and vasa recta both use countercurrent arrangements. Explain how one creates the medullary gradient while the other preserves it.

  5. An FRQ asks you to trace the path of a glucose molecule from the glomerulus back to the bloodstream. Which structures are involved, and what transport mechanisms move glucose at each step?