Nephron
● Structural and functional unit of the kidney.
● Each kidney has about 1–1.5 million nephrons.
● Two parts – glomerulus and renal tubule.
Glomerulus
● Tuft of capillaries formed by afferent arteriole.
● Capillaries reunite to form efferent arteriole.
● Afferent wider than efferent → creates high pressure for filtration.
Bowman’s Capsule
● Double-walled cup-shaped structure.
● Inner visceral layer – has podocytes with pedicels forming filtration slits.
● Outer parietal layer – simple squamous epithelium.
● Space between them is capsular space.
● Glomerulus + Bowman’s capsule = Malpighian body.
Proximal Convoluted Tubule (PCT)
● Highly coiled, in the cortex.
● Cuboidal epithelial cells with microvilli (brush border).
● Rich in mitochondria.
● Reabsorbs 70–80% water and salts, glucose, amino acids.
● Secretes H⁺ and NH₃ to maintain pH.
Loop of Henle
● U-shaped, dips into medulla.
● Descending limb – permeable to water, impermeable to solutes.
● Ascending limb – impermeable to water, transports Na⁺, Cl⁻.
● Helps in urine concentration by creating osmotic gradient.
Distal Convoluted Tubule (DCT)
● Short, coiled, in cortex.
● Cuboidal epithelium without brush border.
● Selective reabsorption of Na⁺, Cl⁻, HCO₃⁻.
● Secretes H⁺, K⁺, NH₃ for pH regulation.
● Controlled by aldosterone.
Collecting Duct
● Receives fluid from many DCTs.
● Passes through cortex and medulla to renal pelvis.
● Reabsorbs water under ADH.
● Recycles urea into medulla.
● Maintains pH by secreting H⁺ and K⁺.
Vasa Recta
● U-shaped capillaries around Loop of Henle.
● Maintains osmotic gradient.
● Well developed in juxtamedullary nephrons.
Types of Nephrons
● Cortical nephrons (85%) – short loop, poor vasa recta.
● Juxtamedullary nephrons – long loop, deep into medulla, maintain urine
concentration.
Juxtaglomerular Apparatus (JGA)
● Located where DCT contacts afferent arteriole.
● Contains macula densa, JG cells, and lacis cells.
● JG cells secrete renin when blood pressure drops.
● Renin → Angiotensin → Aldosterone → raises BP and restores GFR.
Urine Formation
Steps
1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion
1. Glomerular Filtration
● Blood filtered under pressure (GHP = 60 mmHg).
● Opposing pressures: BCOP = 30 mmHg, CHP = 20 mmHg.
● Net filtration pressure = 10 mmHg.
● Filtration membrane: endothelium, basement membrane, podocytes.
● GFR: 125 mL/min = 180 L/day.
● Filtration fraction: 18%.
● Autoregulation: myogenic mechanism, JGA, neural control.
2. Tubular Reabsorption
● 99% filtrate reabsorbed.
● Active (Na⁺, glucose) and passive (water, urea) reabsorption.
● Major sites:
○ PCT: bulk reabsorption.
○ Loop of Henle: osmotic regulation.
○ DCT/CD: hormonal control (ADH, aldosterone).
3. Tubular Secretion
● Active removal of wastes from blood into tubule.
● Secretes: H⁺, K⁺, NH₃, organic acids.
● Functions: acid-base balance, ion regulation, detoxification.
Functions of Tubules
Proximal Convoluted Tubule
● Reabsorbs water, Na⁺, glucose, amino acids, vitamins.
● Secretes H⁺ and NH₃.
● Maintains pH and ionic balance.
● Performs isotonic reabsorption.
Loop of Henle
● Descending limb: reabsorbs water, filtrate becomes hypertonic.
● Ascending limb: reabsorbs NaCl, filtrate becomes hypotonic.
● Creates osmotic gradient for concentration.
Distal Convoluted Tubule
● Reabsorbs Na⁺ and water under aldosterone and ADH.
● Reabsorbs HCO₃⁻, secretes H⁺, K⁺, NH₃.
● Fine-tunes pH and ion balance.
Collecting Duct
● Reabsorbs water (under ADH).
● Partially reabsorbs urea for medullary gradient.
● Secretes H⁺, K⁺.
● Produces final urine.
Mechanism of Concentration of the Filtrate
● Depends on Loop of Henle and Vasa Recta.
● Creates osmotic gradient (cortex 300 → medulla 1200 mOsm/L).
● Solutes: NaCl and urea.
Loop of Henle
● Counter-current multiplier.
● Descending limb: water leaves → filtrate concentrated.
● Ascending limb: NaCl leaves → filtrate diluted.
Vasa Recta
● Counter-current exchanger.
● Maintains medullary hyperosmolarity.
● Descending limb: gains solutes, loses water.
● Ascending limb: gains water, loses solutes.
Urea Recycling
● Urea diffuses from collecting duct → interstitium → thin ascending limb.
● Maintains medullary osmolarity.
Result
● Establishes medullary osmotic gradient.
● Enables ADH-mediated water reabsorption.
● Produces concentrated urine (~1200 mOsm/L).
Regulation of Kidney Function
1. ADH (Vasopressin)
● Secreted by posterior pituitary.
● Triggered by osmoreceptors in hypothalamus.
● Increases water permeability of DCT and CD.
● Promotes water reabsorption → concentrated urine.
● Deficiency causes diabetes insipidus (polyuria, thirst).
● Excess → vasoconstriction and ↑BP.
2. Juxtaglomerular Apparatus (RAAS)
● Low BP or GFR → renin release by JG cells.
● Renin → converts angiotensinogen → angiotensin I.
● ACE (lungs) converts it to angiotensin II.
● Angiotensin II: vasoconstriction, ↑BP, stimulates aldosterone.
● Aldosterone: reabsorbs Na⁺ and water, secretes K⁺.
● Increases blood volume and BP, restores GFR.
3. Atrial Natriuretic Factor (ANF)
● Secreted by atria of heart.
● Trigger: high BP or blood volume.
● Causes vasodilation, ↓BP.
● Inhibits renin, aldosterone, and ADH.
● Promotes Na⁺ and water excretion → dilute urine.
● Opposes RAAS and ADH effects.
Micturition
● Process of urine expulsion from bladder via urethra.
● Controlled by micturition reflex.
Storage Phase
● Detrusor muscle relaxed, sphincters closed.
● Stretch receptors inactive.
Voiding Reflex
● 300–400 mL urine → stretch receptors activated.
● Afferent impulses → spinal cord → parasympathetic impulses.
● Detrusor contracts, internal sphincter relaxes.
● Urge to urinate begins.
Voluntary Control
● External sphincter (skeletal muscle) under cerebral control.
● Relaxation → urine expelled.
● Controlled by sacral, pontine, and cortical centers.
Abnormalities
● Anuria: no urine (<100 mL/day).
● Oliguria: low urine (100–400 mL/day).
● Polyuria: excessive urine (>2.5 L/day).
● Dysuria: painful urination.
● Retention: incomplete emptying.
● Incontinence: loss of control.
Composition of Normal Urine
● Color: Pale yellow (urochrome).
● Odor: Aromatic → ammoniacal on standing.
● pH: ~6.0 (range 4.5–8.0).
● Specific gravity: 1.003–1.035.
● Water: 95%.
● Solutes: 5% (urea, uric acid, creatinine, salts).
Abnormal Constituents
● Glucose: diabetes mellitus.
● Albumin: nephritis.
● Ketones: fat metabolism.
● Blood: injury or infection.
● Pus cells: UTI.
● Bile pigments: liver disease.
● Crystals: kidney stones.
Disorders of Excretory System
● Uremia: urea accumulation → dialysis/transplant.
● Renal Failure: loss of kidney function.
○ Acute: sudden, reversible.
○ Chronic: slow, irreversible.
● Renal Calculi: stones (Ca oxalate, uric acid).
● Glomerulonephritis: glomerular inflammation (often streptococcal).
● Symptoms: proteinuria, hematuria, edema.
● Dialysis: artificial waste removal.
Artificial Kidney / Haemodialysis
Need
● Used in renal failure when kidneys can’t remove wastes.
● Prevents uremic poisoning.
Principle
● Works on diffusion through a semipermeable membrane.
● Wastes move from blood → dialysate.
Components
● Dialyzer: semipermeable tubes (cellulose fibers).
● Dialysate: contains salts, glucose, no nitrogen wastes.
● Blood circuit: artery → dialyzer → vein.
● Anticoagulant: heparin prevents clotting.
● Controls: maintain pressure and temperature.
Process
1. Blood withdrawn from artery.
2. Passes through dialyzer with counter-current flow.
3. Wastes diffuse out, clean blood returns to body.
4. Done 2–3 times/week, 4–6 hours/session.
Advantages
● Life-saving for renal failure.
● Removes urea, salts, toxins.
● Maintains acid-base balance.
● Buys time for transplant.
Limitations
● Expensive, time-consuming.
● Risk of infection and nutrient loss.
● Not a permanent cure.
Peritoneal Dialysis
● Uses peritoneum as natural membrane.
● Dialysis fluid introduced into abdominal cavity.
● Wastes diffuse → fluid drained and replaced.
● Home-based, continuous, no anticoagulant needed.
● Risk of peritonitis.
● Less efficient than haemodialysis.