Renal Physiology and Urine Formation

Tubular Reabsorption

  • Selective transepithelial process.
  • All organic nutrients are reabsorbed.
  • Water and ion reabsorption are hormonally regulated.
  • Includes both active and passive processes.
  • Occurs via two routes:
    • Transcellular: Movement through the tubule cells.
    • Paracellular: Movement between tubule cells.

Transcellular vs. Paracellular Routes

  • Transcellular Route:
    • Involves transport across the luminal membrane, diffusion through the cytosol, transport across the basolateral membrane, and movement through the interstitial fluid into the capillary.
  • Paracellular Route:
    • Involves movement through leaky tight junctions, particularly in the proximal convoluted tubule (PCT).

Key Steps in Reabsorption

  • Step 1: Transport across the luminal membrane.
  • Step 2: Diffusion through the cytosol.
  • Step 3: Transport across the basolateral membrane (often involving the lateral intercellular spaces).
  • Step 4: Movement through the interstitial fluid and into the capillary.

Na+ Transport and Concentration Gradients

  • At the basolateral membrane, Na^+ is actively pumped into the interstitial space by the Na^+-K^+ ATPase.
  • Active Na+ transport creates concentration gradients that drive:
    • "Downhill" Na^+ entry at the luminal membrane.
    • Reabsorption of water by osmosis.
    • Reabsorption of organic nutrients and certain ions by cotransport at the luminal membrane.
    • Diffusion of lipid-soluble substances via the transcellular route.
    • Diffusion of Cl^−, K^+, and urea via the paracellular route.

Reabsorption Mechanisms

  • Primary Active Transport:
    • Example: Na^+-K^+ ATPase pump.
  • Secondary Active Transport:
    • Reabsorption of organic nutrients and ions via cotransport with Na^+.
  • Passive Transport (Diffusion):
    • Lipid-soluble substances (transcellular).
    • Cl^−, Ca^{2+}, K^+, and urea (paracellular).
    • Water (osmosis).

Regulation of Urine Concentration and Volume

  • Osmolality: Number of solute particles in 1 kg of H_2O. Reflects the ability to cause osmosis.
  • Osmolality is expressed in milliosmols (mOsm).
  • The kidneys maintain plasma osmolality at ~300 mOsm using countercurrent mechanisms.

Countercurrent Mechanism

  • Occurs when fluid flows in opposite directions in two adjacent segments of the same tube.
  • Examples:
    • Filtrate flow in the loop of Henle (countercurrent multiplier).
    • Blood flow in the vasa recta (countercurrent exchanger).

Role of Countercurrent Mechanisms

  • Establish and maintain an osmotic gradient (300 mOsm to 1200 mOsm) from the renal cortex through the medulla.
  • Allow the kidneys to vary urine concentration.

Countercurrent Multiplier

  • The long loops of Henle of the juxtamedullary nephrons create the medullary osmotic gradient.
  • Descending Limb:
    • Permeable to H_2O. Impermeable to NaCl.
    • As filtrate flows, it becomes increasingly concentrated as H_2O leaves the tubule by osmosis.
    • Filtrate osmolality increases from 300 to 1200 mOsm.
  • Ascending Limb:
    • Impermeable to H_2O. Permeable to NaCl.
    • Filtrate becomes increasingly dilute as NaCl leaves, eventually becoming hypo-osmotic to blood at 100 mOsm in the cortex.
    • NaCl leaving the ascending limb increases the osmolality of the medullary interstitial fluid.
  • Filtrate entering the loop of Henle is isosmotic to both blood plasma and cortical interstitial fluid.

Urea Recycling

  • Urea moves between the collecting ducts and the loop of Henle.
  • Secreted into filtrate by facilitated diffusion in the ascending thin segment.
  • Reabsorbed by facilitated diffusion in the collecting ducts deep in the medulla.
  • Contributes to the high osmolality in the medulla.

Countercurrent Exchanger: Vasa Recta

  • The vasa recta maintain the osmotic gradient.
  • Deliver blood to the medullary tissues.
  • Protect the medullary osmotic gradient by preventing rapid removal of salt and by removing reabsorbed H_2O.
  • Highly permeable to H_2O and solute.
  • Nearly isosmotic to interstitial fluid due to sluggish blood flow.
  • Blood becomes more concentrated as it descends deeper into the medulla and less concentrated as it approaches the cortex.

Formation of Dilute Urine

  • Filtrate is diluted in the ascending loop of Henle.
  • In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine.
  • Na^+ and other ions may be selectively removed in the DCT and collecting duct, decreasing osmolality to as low as 50 mOsm.

Formation of Concentrated Urine

  • Depends on the medullary osmotic gradient and ADH.
  • ADH triggers reabsorption of H_2O in the collecting ducts.

Diuretics

  • Chemicals that enhance urinary output.
    • Osmotic diuretics: substances not reabsorbed (e.g., high glucose in a diabetic patient).
    • ADH inhibitors: alcohol.
    • Substances that inhibit Na^+ reabsorption and obligatory H_2O reabsorption: caffeine and many drugs.

Reabsorption in Different Tubule Segments

  • Proximal Convoluted Tubule (PCT):
    • 65% of filtrate volume reabsorbed.
    • Na^+, glucose, amino acids, and other nutrients actively transported; H_2O and many ions follow passively.
    • H^+ and NH4^+ secretion and HCO3^− reabsorption to maintain blood pH.
    • Some drugs are secreted.
  • Descending Limb of Loop of Henle:
    • Freely permeable to H_2O. Not permeable to NaCl.
    • Filtrate becomes increasingly concentrated as H_2O leaves by osmosis.
  • Ascending Limb of Loop of Henle:
    • Impermeable to H_2O. Permeable to NaCl.
    • Filtrate becomes increasingly dilute as salt is reabsorbed.
  • Distal Convoluted Tubule (DCT):
    • Na^+ reabsorption regulated by aldosterone.
    • Ca^{2+} reabsorption regulated by parathyroid hormone (PTH).
    • Cl^− cotransported with Na^+.
  • Collecting Duct:
    • H_2O reabsorption through aquaporins regulated by ADH.
    • Na^+ reabsorption and K^+ secretion regulated by aldosterone.
    • H^+ and HCO_3^− reabsorption or secretion to maintain blood pH.
    • Urea reabsorption increased by ADH.

Physical Characteristics of Urine

  • Color and Transparency:
    • Clear, pale to deep yellow (due to urochrome).
    • Drugs, vitamin supplements, and diet can alter the color.
    • Cloudy urine may indicate a urinary tract infection.
  • Odor:
    • Slightly aromatic when fresh.
    • Develops ammonia odor upon standing.
    • May be altered by some drugs and vegetables.
  • pH:
    • Slightly acidic (~pH 6, with a range of 4.5 to 8.0).
    • Diet, prolonged vomiting, or urinary tract infections may alter pH.
  • Specific Gravity:
    • 1.001 to 1.035, dependent on solute concentration.

Chemical Composition of Urine

  • 95% water and 5% solutes.
    • Nitrogenous wastes: urea, uric acid, and creatinine.
    • Other normal solutes: Na^+, K^+, PO4^{3−}, SO4^{2−}, Ca^{2+}, Mg^{2+}, and HCO_3^−.
  • Abnormally high concentrations of any constituent may indicate pathology.

Abnormal Urinary Constituents

  • Glucose (Glycosuria):
    • Possible cause: Diabetes mellitus.
  • Proteins (Proteinuria or Albuminuria):
    • Nonpathological causes: excessive physical exertion, pregnancy, high-protein diet.
    • Pathological causes: heart failure, severe hypertension, glomerulonephritis, often initial sign of asymptomatic renal disease.
  • Ketone Bodies (Ketonuria):
    • Possible cause: Excessive formation and accumulation of ketone bodies, as in starvation and untreated diabetes mellitus.
  • Hemoglobin (Hemoglobinuria):
    • Possible causes: transfusion reaction, hemolytic anemia, severe burns, etc.
  • Bile Pigments (Bilirubinuria):
    • Possible causes: Liver disease (hepatitis, cirrhosis) or obstruction of bile ducts from liver or gallbladder.
  • Erythrocytes (Hematuria):
    • Possible causes: Bleeding urinary tract (due to trauma, kidney stones, infection, or neoplasm).
  • Leukocytes (Pyuria):
    • Possible cause: Urinary tract infection.

Ureters

  • Convey urine from kidneys to bladder.
  • Retroperitoneal.
  • Enter the base of the bladder through the posterior wall.
  • As bladder pressure increases, distal ends of the ureters close, preventing backflow of urine.
  • Three layers of the wall:
    • Lining of transitional epithelium.
    • Smooth muscle muscularis (contracts in response to stretch).
    • Outer adventitia of fibrous connective tissue.

Renal Calculi

  • Kidney stones form in renal pelvis.
  • Crystallized calcium, magnesium, or uric acid salts.
  • Larger stones block ureter, cause pressure and pain in kidneys.
  • May be due to chronic bacterial infection, urine retention, increased Ca^{2+} in blood, or altered pH of urine.

Urinary Bladder

  • Muscular sac for temporary storage of urine.
  • Retroperitoneal, on pelvic floor posterior to pubic symphysis.
    • Males—prostate gland surrounds the neck inferiorly.
    • Females—anterior to the vagina and uterus.
  • Layers of the bladder wall:
    • Transitional epithelial mucosa.
    • Thick detrusor muscle (three layers of smooth muscle).
    • Fibrous adventitia (peritoneum on superior surface only).
  • Collapses when empty; rugae appear.
  • Expands and rises superiorly during filling without significant rise in internal pressure.
  • Trigone:
    • Smooth triangular area outlined by the openings for the ureters and the urethra.
    • Infections tend to persist in this region.

Micturition

  • Urination or voiding.
  • Three simultaneous events:
    • Contraction of detrusor muscle by ANS.
    • Opening of internal urethral sphincter by ANS.
    • Opening of external urethral sphincter by somatic nervous system.