Medical School · Year 2 · Renal · includes a quiz and discussion video

Lecture 1: Renal Anatomy and Histology

Unit 2.1: Renal System

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the gross anatomy of the kidneys and urinary tract
2. Identify the components of the nephron and their functions
3. Describe the renal vasculature and its unique features
4. Explain the histology of glomerular and tubular structures
5. Describe the juxtaglomerular apparatus and its role
6. Correlate renal structure with function

Gross Anatomy of the Kidney

The kidneys are essential organs responsible for filtration, homeostasis, and endocrine functions. Understanding their anatomical relationships and internal organization provides the foundation for comprehending renal physiology and pathology.

Location and Relations

The kidneys occupy a retroperitoneal position on the posterior abdominal wall, extending from approximately the T12 to L3 vertebral levels. The right kidney sits slightly lower than the left due to the presence of the liver superiorly. Each kidney measures approximately 11 cm long, 6 cm wide, and 3 cm thick, weighing about 150 grams. Important anatomical relations include the adrenal glands capping the superior poles, the liver on the right and spleen on the left, segments of the colon anteriorly, and the diaphragm superoposteriorly.

External Features

The hilum is the medial indentation where the renal vessels, nerves, lymphatics, and ureter enter or exit the kidney. The renal artery enters posterior to the renal vein, which lies anterior to the renal pelvis. A fibrous renal capsule provides the immediate covering of the kidney parenchyma. Perirenal fat surrounds the kidney within the renal fascia (Gerota's fascia), which also encloses the adrenal gland within the same compartment.

Internal Structure

When sectioned coronally, the kidney reveals distinct regions. The cortex is the outer granular-appearing layer containing all glomeruli, proximal and distal convoluted tubules, and cortical portions of collecting ducts. The medulla comprises the inner region, organized into conical renal pyramids with their bases at the corticomedullary junction and apices (papillae) projecting into the minor calyces. The medulla contains loops of Henle, medullary collecting ducts, and vasa recta. Columns of Bertin are extensions of cortical tissue extending between pyramids. The minor calyces cup the papillae and collect urine, merging to form two to three major calyces, which in turn drain into the funnel-shaped renal pelvis continuing as the ureter.

<image>Panel A: Coronal section of the kidney showing the outer cortex in reddish-brown with granular texture containing glomeruli and convoluted tubules. Panel B: Inner medulla with triangular pyramids (8-12) showing striations of collecting ducts converging toward papillae, with columns of Bertin extending between pyramids. Panel C: Collecting system with minor calyces surrounding each papilla, merging into major calyces that drain into the funnel-shaped renal pelvis at the hilum. Panel D: Hilum structures showing the renal artery entering posteriorly, renal vein anteriorly, ureter emerging from the pelvis, fibrous capsule, and surrounding perirenal fat.</image>

Renal Vasculature

The kidney receives 20-25% of cardiac output despite comprising less than 1% of body weight, reflecting the organ's primary filtration function. The vascular architecture is uniquely organized to support both filtration and tubular reabsorption.

Arterial Supply

The renal artery arises from the aorta at the L1-L2 level and enters the kidney at the hilum. It divides into five segmental arteries, each supplying a distinct renal segment without collateral circulation—making these end arteries where occlusion leads to infarction. Segmental arteries branch into interlobar arteries that course between pyramids toward the cortex. At the corticomedullary junction, interlobar arteries become arcuate arteries that arch along this border. Interlobular arteries (also called cortical radiate arteries) ascend through the cortex, giving rise to afferent arterioles that supply individual glomeruli.

The Two Capillary Beds

The kidney is unique in possessing two capillary beds arranged in series. The glomerular capillaries are high-pressure, fenestrated vessels optimized for filtration. Blood exits the glomerulus via the efferent arteriole, which then supplies either peritubular capillaries (surrounding cortical tubules and facilitating reabsorption) or the vasa recta (paralleling medullary loops of Henle). This arrangement allows independent regulation of filtration and reabsorption.

Venous Drainage

Venous drainage parallels the arterial supply in reverse: interlobular veins drain to arcuate veins, then interlobar veins, and finally the renal vein. The left renal vein is longer, crossing anterior to the aorta to reach the inferior vena cava, and receives the left gonadal and left adrenal veins.

Vasa Recta

The vasa recta are specialized capillaries arising from efferent arterioles of juxtamedullary nephrons. They descend parallel to the loops of Henle into the medulla before looping back toward the cortex. This hairpin configuration enables countercurrent exchange, which preserves the medullary osmotic gradient essential for urine concentration while still delivering oxygen and nutrients.

<image>Panel A: Arterial branching pattern from aorta through renal artery to segmental arteries (5 branches), interlobar arteries between pyramids, arcuate arteries at corticomedullary junction, and interlobular arteries ascending through cortex to afferent arterioles. Panel B: Magnified glomerulus showing afferent arteriole entering, glomerular capillary tuft, and efferent arteriole exiting. Panel C: Two capillary beds in series with glomerular capillaries (high-pressure filtration) connecting via efferent arteriole to peritubular capillaries (low-pressure reabsorption) around cortical tubules. Panel D: Vasa recta descending into the medulla alongside loop of Henle for countercurrent exchange, with blood flow noted as 20-25% of cardiac output.</image>

The Nephron Overview

The nephron is the functional unit of the kidney, with approximately one million nephrons per kidney. Each nephron consists of a renal corpuscle for filtration and a tubular system for modifying the filtrate.

Nephron Components

The renal corpuscle comprises the glomerulus (a capillary tuft) and Bowman's capsule (a cup-like structure collecting filtrate), together responsible for ultrafiltration. The proximal convoluted tubule (PCT) performs bulk reabsorption, recovering approximately 65-70% of filtered sodium, water, glucose, amino acids, and bicarbonate. The loop of Henle creates the medullary concentration gradient through its descending and ascending limbs. The distal convoluted tubule (DCT) performs fine-tuning of sodium, calcium, and other electrolytes under hormonal regulation. The collecting duct traverses from cortex to medullary papilla, performing final concentration or dilution of urine under ADH control and acid-base regulation.

Nephron Types

Two populations of nephrons exist based on location. Cortical nephrons (85%) have glomeruli in the outer cortex and short loops of Henle that extend only into the outer medulla. Juxtamedullary nephrons (15%) have glomeruli near the corticomedullary junction and long loops of Henle that extend deep into the inner medulla, reaching the papillary tip. These juxtamedullary nephrons are essential for maximum urinary concentration, as their long loops contribute to establishing the full medullary gradient.

<image>Panel A: Complete nephron with labeled segments including renal corpuscle (Bowman's capsule surrounding glomerulus), proximal convoluted tubule with brush-bordered eosinophilic cells, and descending thin limb with simple squamous epithelium. Panel B: Continuation of nephron segments showing ascending thin limb, thick ascending limb with cuboidal cells, distal convoluted tubule without brush border, connecting tubule, and collecting duct. Panel C: Cortical nephron (85%) with short loop barely entering outer medulla and peritubular capillaries surrounding tubules. Panel D: Juxtamedullary nephron (15%) with glomerulus near corticomedullary junction, long loop extending to papillary tip, and vasa recta paralleling the loop through demarcated cortex, outer medulla, and inner medulla zones.</image>

Renal Corpuscle

The renal corpuscle is the site of plasma ultrafiltration, producing approximately 180 liters of filtrate daily. Its specialized structure creates a selective filtration barrier.

Structure

The glomerulus is a tuft of anastomosing capillaries derived from the afferent arteriole and draining into the efferent arteriole. Bowman's capsule is a double-layered epithelial cup surrounding the glomerulus. The parietal layer is simple squamous epithelium lining the outer capsule. The visceral layer consists of podocytes (specialized epithelial cells) intimately associated with glomerular capillaries. Bowman's space is the cavity between these layers where filtrate collects before entering the proximal tubule.

The Filtration Barrier

The filtration barrier is a three-layered structure determining what passes from blood into Bowman's space. The glomerular endothelium consists of fenestrated endothelial cells with pores of 70-100 nm lacking diaphragms. These fenestrae allow free passage of plasma but retain blood cells. The glomerular basement membrane (GBM) is a specialized extracellular matrix composed of type IV collagen (providing structural framework), laminin (for cell attachment), nidogen (cross-linking components), and heparan sulfate proteoglycans (providing negative charge that repels negatively charged proteins like albumin). The podocytes (visceral epithelium) extend foot processes (pedicels) that interdigitate around capillaries, connected by slit diaphragms containing nephrin, podocin, and other proteins that form the final size-selective barrier.

Together, these layers create a barrier that is freely permeable to water and small solutes but restricts passage of proteins larger than albumin (approximately 69 kDa) and maintains charge selectivity that limits filtration of negatively charged molecules.

<image>Panel A: Renal corpuscle cross-section showing glomerular capillary tuft within Bowman's capsule, with parietal layer of flat squamous cells lining the outer capsule and visceral layer of podocytes covering the capillaries. Panel B: Bowman's space separating layers with filtrate flow arrows, vascular pole showing afferent arteriole entering and efferent arteriole exiting, and urinary pole transitioning to proximal tubule. Panel C: Electron microscopy view of filtration barrier showing fenestrated endothelium with 70-100 nm pores and trilaminar GBM (lamina rara externa, lamina densa, lamina rara interna). Panel D: Podocyte foot processes with slit diaphragms (20-40 nm) between them, filtration direction arrows, and negative charges depicted as minus signs on heparan sulfate of GBM.</image>

Glomerular Cells

Four cell types contribute to glomerular structure and function, each with distinct roles in maintaining filtration and responding to injury.

Endothelial Cells

Glomerular endothelial cells are highly fenestrated, with pores that lack the diaphragms seen in most other fenestrated capillaries. This allows high hydraulic conductivity for filtration. The glycocalyx coating these cells contributes to the charge barrier. Endothelial cell injury (as in thrombotic microangiopathies) disrupts the filtration barrier.

Podocytes

Podocytes are terminally differentiated epithelial cells of the visceral layer. The cell body floats in Bowman's space, projecting primary processes that further divide into secondary foot processes (pedicels). Adjacent foot processes interdigitate in a zipper-like pattern, connected by slit diaphragms. The slit diaphragm is a specialized cell junction containing nephrin, podocin, CD2AP, and other proteins essential for barrier function. Podocyte injury, detachment, or loss leads to proteinuria, as seen in minimal change disease, focal segmental glomerulosclerosis, and diabetic nephropathy. Because podocytes cannot regenerate significantly, their loss is particularly consequential.

Mesangial Cells

Intraglomerular mesangial cells reside between capillary loops, supported by mesangial matrix. They provide structural support for the glomerular tuft. Being contractile (containing actin and myosin), they can regulate filtration surface area in response to vasoactive substances. Mesangial cells are phagocytic, clearing trapped macromolecules and immune complexes from the GBM. They also produce growth factors, cytokines, and matrix components. Mesangial proliferation and matrix expansion are features of IgA nephropathy and diabetic nephropathy.

Parietal Epithelial Cells

These simple squamous cells line Bowman's capsule. They transition to podocytes at the vascular pole and to proximal tubular epithelium at the urinary pole. Recent evidence suggests parietal epithelial cells may serve as progenitors for podocyte replacement in some conditions.

<image>Panel A: Cross-section of glomerular capillary loop showing endothelial cells with fenestrations lining the lumen and GBM separating endothelium from epithelium. Panel B: Podocyte with cell body in Bowman's space and foot processes contacting GBM, with inset magnifying slit diaphragm showing nephrin and podocin proteins spanning between adjacent foot processes. Panel C: Mesangial cells (stellate-shaped) between capillary loops surrounded by mesangial matrix, with arrows indicating functions of structural support, contraction, and phagocytosis. Panel D: Parietal epithelial cells lining outer capsule with transition zone at urinary pole where parietal cells become proximal tubule cells.</image>

Proximal Tubule

The proximal tubule is responsible for the bulk reabsorption of filtered solutes and water, recovering approximately 65-70% of the glomerular filtrate.

Structure

The proximal tubule is divided into three segments: S1 (early convoluted portion), S2 (late convoluted portion), and S3 (straight portion or pars recta descending toward the medulla). The total length is approximately 14 mm. Histologically, the epithelium is simple cuboidal with prominent eosinophilic (pink-staining) cytoplasm due to abundant mitochondria. Cell boundaries appear indistinct on light microscopy because of extensive lateral interdigitation.

Histologic Features Reflecting Function

The brush border (apical microvilli) dramatically increases surface area for reabsorption, creating the "brush border" appearance on microscopy. This is the most distinctive feature distinguishing proximal from distal tubule. Abundant mitochondria provide ATP for active transport, particularly powering the basolateral Na⁺/K⁺-ATPase. Basolateral membrane infoldings increase surface area for the numerous transporters located there. Lateral intercellular spaces accommodate the large volumes of fluid moving through the paracellular pathway.

Functions

The proximal tubule performs massive reabsorption of nearly all useful filtered substances. Sodium reabsorption (65-70%) is coupled to glucose, amino acids, phosphate, and bicarbonate via apical cotransporters, driven by the low intracellular sodium concentration established by basolateral Na⁺/K⁺-ATPase. Water reabsorption (65%) follows passively via aquaporin-1 channels, which are constitutively active (not regulated by hormones). Glucose reabsorption is essentially complete under normal conditions via SGLT2 (90%) and SGLT1 (10%). Amino acids are nearly completely reabsorbed (99%) via multiple transporters. Bicarbonate reabsorption (80-90%) occurs through the action of carbonic anhydrase. The proximal tubule also secretes organic anions and cations, including drugs and toxins.

<image>Panel A: Light microscopy comparing proximal tubule (PT) with prominent eosinophilic cells, indistinct borders, and brush border narrowing the lumen versus distal tubule (DT) with clearer borders, less eosinophilic cytoplasm, no brush border, and wider lumen. Panel B: Proximal tubule cell apical surface with tall microvilli (brush border) and labeled transporters including SGLT2 for glucose, NHE3 sodium-hydrogen exchanger, and amino acid cotransporters. Panel C: Proximal tubule cell cytoplasm with densely packed mitochondria and basolateral membrane showing extensive infoldings with Na+/K+-ATPase (3 Na+ out, 2 K+ in). Panel D: Transport direction arrows showing glucose, amino acids, Na+, and water moving from lumen to interstitium, with bar graph of reabsorption percentages (Na+ 65-70%, water 65%, glucose 100%, amino acids 99%, HCO3- 80-90%).</image>

Loop of Henle

The loop of Henle extends from the cortex into the medulla and back, establishing the osmotic gradient necessary for urine concentration.

Segments

The thin descending limb is lined by simple squamous epithelium with few organelles, reflecting limited metabolic activity. It is highly permeable to water (via aquaporin-1) but has low permeability to sodium chloride. As tubular fluid descends into the hyperosmotic medulla, water exits passively, concentrating the tubular fluid.

The thin ascending limb, present only in long-looped (juxtamedullary) nephrons, is also simple squamous epithelium but lacks aquaporins, making it impermeable to water. It has moderate permeability to sodium chloride, which diffuses passively into the increasingly less concentrated interstitium as fluid ascends.

The thick ascending limb (TAL) consists of cuboidal epithelium with abundant mitochondria reflecting high metabolic activity. It actively reabsorbs approximately 25% of filtered sodium via the NKCC2 transporter (Na⁺-K⁺-2Cl⁻ cotransporter) on the apical membrane. Critically, it is completely impermeable to water, earning it the name "diluting segment"—fluid becomes progressively hypotonic as solute is removed without water following.

NKCC2 and Potassium Recycling

The NKCC2 transporter requires all three ions (Na⁺, K⁺, and Cl⁻) for function. Because luminal potassium concentration is limiting, potassium is recycled back into the lumen via ROMK potassium channels. This recycling generates a lumen-positive electrical potential that drives paracellular reabsorption of calcium and magnesium. Loop diuretics (furosemide, bumetanide) block NKCC2, inhibiting sodium reabsorption, abolishing the lumen-positive potential (causing calcium and magnesium wasting), and impairing the medullary gradient (reducing concentrating ability).

<image>Panel A: Thin descending limb with simple squamous cells showing water arrows exiting toward increasingly hyperosmotic interstitium (300 to 600 to 1200 mOsm/kg). Panel B: Thin ascending limb with NaCl arrows exiting passively and water impermeable symbol, followed by thick ascending limb with cuboidal cells performing active NaCl transport. Panel C: Magnified thick ascending limb cell showing apical NKCC2 (1 Na+, 1 K+, 2 Cl- entering) and ROMK channel recycling K+ to lumen creating lumen-positive potential. Panel D: Basolateral Na+/K+-ATPase and Cl- channels with paracellular Ca2+ and Mg2+ reabsorption driven by lumen-positive potential, and furosemide blocking NKCC2.</image>

Distal Tubule and Collecting Duct

These segments perform fine-tuning of electrolytes and final concentration or dilution of urine under hormonal control.

Distal Convoluted Tubule

The DCT is lined by cuboidal epithelium lacking a brush border, distinguishing it from the proximal tubule. Cells have abundant mitochondria for active transport. The apical NCC transporter (Na⁺-Cl⁻ cotransporter) mediates sodium and chloride reabsorption, accounting for approximately 5% of filtered sodium. Thiazide diuretics block NCC.

The DCT is the major site of regulated calcium reabsorption. Calcium enters through apical TRPV5 channels, binds intracellular calbindin for transport across the cell, and exits via basolateral NCX (Na⁺/Ca²⁺ exchanger) and Ca²⁺-ATPase. Parathyroid hormone increases calcium reabsorption by upregulating these components. Interestingly, thiazide diuretics increase calcium reabsorption (useful in treating hypercalciuria) by lowering intracellular sodium, which enhances NCX-mediated calcium exit.

Collecting Duct Cells

The collecting duct traverses from cortex through outer and inner medulla to the papilla. Two main cell types are present. Principal cells (light-staining) possess apical ENaC (epithelial sodium channel) for sodium reabsorption and ROMK channels for potassium secretion, plus aquaporin-2 on the apical membrane for ADH-regulated water reabsorption. Basolateral aquaporins-3 and -4 are constitutively present. Aldosterone increases ENaC and Na⁺/K⁺-ATPase expression, enhancing sodium reabsorption and potassium secretion.

Intercalated cells (dark-staining) regulate acid-base balance. Type A intercalated cells secrete H⁺ via apical H⁺-ATPase while reabsorbing bicarbonate via basolateral Cl⁻/HCO₃⁻ exchanger (AE1)—active in acidosis. Type B intercalated cells do the opposite: secrete bicarbonate apically and reabsorb H⁺ via basolateral H⁺-ATPase—active in alkalosis.

Drugs Targeting the Collecting Duct

Potassium-sparing diuretics act here: amiloride and triamterene directly block ENaC, while spironolactone and eplerenone block the mineralocorticoid receptor, preventing aldosterone's effects.

<image>Panel A: DCT cell with apical NCC transporter (Na+ and Cl- entering), basolateral Na+/K+-ATPase and Cl- channels, and thiazide blocking NCC. Panel B: Calcium transport pathway in DCT showing apical TRPV5, intracellular calbindin, and basolateral NCX plus Ca2+-ATPase, with PTH stimulating these components. Panel C: Collecting duct principal cell with apical ENaC (Na+ in), ROMK (K+ out), AQP2 (water in when ADH present), basolateral Na+/K+-ATPase and AQP3/4, and aldosterone stimulating ENaC. Panel D: Intercalated cells showing Type A with apical H+-ATPase and basolateral AE1 for acid secretion, Type B with reversed polarity for base secretion, and drug icons showing amiloride blocking ENaC and spironolactone blocking MR.</image>

Juxtaglomerular Apparatus

The juxtaglomerular apparatus (JGA) is a specialized structure at the vascular pole of the glomerulus that regulates glomerular filtration rate and renin release.

Components

Three cell types constitute the JGA. Juxtaglomerular (JG) cells are modified smooth muscle cells in the wall of the afferent arteriole near the glomerulus. They contain renin-storing granules visible on electron microscopy. JG cells are innervated by sympathetic nerve fibers (β₁-receptors) and release renin in response to decreased renal perfusion pressure (sensed via stretch receptors), decreased NaCl delivery to the macula densa, and sympathetic nervous system activation.

Macula densa cells are specialized epithelial cells of the thick ascending limb where it contacts its own glomerulus. These cells are taller and more closely packed than adjacent TAL cells, with nuclei aligned toward the lumen (hence "macula densa" meaning dense spot). They sense tubular sodium chloride concentration via apical NKCC2 and respond by signaling to JG cells and the afferent arteriole.

Extraglomerular mesangial cells (lacis cells) occupy the triangular space between the afferent arteriole, efferent arteriole, and macula densa. They provide structural support and communication between macula densa and JG cells.

Tubuloglomerular Feedback

This mechanism links tubular flow to glomerular filtration. When GFR increases, more sodium chloride reaches the macula densa. The macula densa senses elevated NaCl via NKCC2 and releases ATP and adenosine. Adenosine causes afferent arteriolar constriction, reducing GFR back toward normal. The converse occurs with decreased GFR: reduced NaCl at the macula densa triggers afferent dilation and renin release, restoring GFR. This negative feedback loop stabilizes GFR despite fluctuations in blood pressure.

<image>Panel A: Vascular pole of glomerulus showing afferent arteriole with JG cells containing renin granules in its wall, efferent arteriole exiting, and glomerular capillaries. Panel B: Thick ascending limb curving back to contact its own glomerulus with macula densa segment (taller cells with crowded nuclei) apposed to afferent arteriole. Panel C: Extraglomerular mesangial cells (lacis cells) filling triangular space between vessels and macula densa with gap junction connections. Panel D: Tubuloglomerular feedback loop showing increased GFR leading to increased NaCl at macula densa, ATP/adenosine release, and afferent constriction; opposite arm showing decreased NaCl leading to afferent dilation and renin release; renin stimuli listed as decreased perfusion pressure, decreased NaCl, and sympathetic activation.</image>

Urinary Tract

The urinary tract conducts urine from the renal pelvis to the external environment and provides storage in the bladder.

Ureter

The ureters are muscular tubes approximately 25 cm long with a diameter of 3-4 mm. The wall consists of three layers: the mucosa lined by transitional epithelium (urothelium), a muscularis with an inner longitudinal and outer circular smooth muscle layer (reversed from the gut), and an outer adventitia. Peristaltic waves propel urine from renal pelvis to bladder.

Three physiological narrowings are clinically important as sites where kidney stones commonly lodge: the ureteropelvic junction (UPJ) where the renal pelvis becomes the ureter, the pelvic brim where the ureter crosses the iliac vessels, and the ureterovesical junction (UVJ) where the ureter enters the bladder.

Urinary Bladder

The bladder is a hollow, distensible muscular organ with capacity of 400-600 mL. The mucosa is lined by transitional epithelium (urothelium) which can stretch from 5-7 cell layers when empty to 2-3 layers when distended. The muscularis (detrusor muscle) consists of three indistinct layers of smooth muscle that contract during micturition. The trigone is a smooth triangular area between the two ureteral orifices and the internal urethral orifice; this region has a different embryological origin and does not expand with filling.

Transitional Epithelium

Urothelium is a specialized stratified epithelium unique to the urinary tract. Surface cells (umbrella cells) are large, dome-shaped, often binucleate, and contain uroplakins—specialized proteins that form plaques creating a highly impermeable barrier against urine. This prevents reabsorption of urinary waste products and protects underlying tissues from the hypertonic, acidic, and potentially toxic urine. The epithelium stretches without increasing permeability—a unique adaptation.

Urethra

The male urethra is approximately 20 cm long, divided into prostatic (through prostate), membranous (through urogenital diaphragm), and spongy (penile) portions. The female urethra is only about 4 cm long, opening anterior to the vagina. This shorter length makes women more susceptible to urinary tract infections.

<image>Panel A: Full urinary system showing kidneys with ureters descending along psoas muscles, crossing iliac vessels at pelvic brim (narrowing marked), entering bladder at posterolateral base with trigone marked between ureteral orifices and internal urethral orifice. Panel B: Male urethra with prostatic, membranous, and spongy segments labeled; inset showing shorter female urethra. Panel C: Ureter wall layers in cross-section showing transitional epithelium mucosa, inner longitudinal muscle, outer circular muscle, and adventitia; three ureteral narrowings marked at UPJ, pelvic brim, and UVJ. Panel D: Transitional epithelium in relaxed state (multiple layers with dome-shaped umbrella cells) versus distended state (stretched thin with flattened umbrella cells), with uroplakin plaques on apical surface of umbrella cells.</image>

Summary

The kidneys are retroperitoneal organs with an outer cortex containing glomeruli and an inner medulla containing pyramids with loops of Henle and collecting ducts.

The nephron is the functional unit, comprising the renal corpuscle for filtration and the tubular system for modification. Cortical nephrons (85%) have short loops, while juxtamedullary nephrons (15%) have long loops essential for maximum urine concentration.

The renal corpuscle consists of the glomerulus and Bowman's capsule. The filtration barrier has three layers: fenestrated endothelium, glomerular basement membrane (providing size and charge selectivity), and podocyte foot processes with slit diaphragms.

Podocyte injury leads to proteinuria. Mesangial cells provide structural support, contract to regulate filtration area, and clear macromolecules.

The proximal tubule has a prominent brush border and performs bulk reabsorption of 65-70% of filtrate. The loop of Henle establishes the medullary gradient, with the thick ascending limb (diluting segment) actively reabsorbing sodium via NKCC2.

The distal convoluted tubule reabsorbs sodium via NCC and is the site of PTH-regulated calcium reabsorption. The collecting duct contains principal cells (sodium reabsorption via ENaC, potassium secretion, ADH-regulated water reabsorption) and intercalated cells (acid-base regulation).

The juxtaglomerular apparatus links tubular sodium sensing (macula densa) to GFR regulation and renin secretion (JG cells).

Key Terms

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