18. PHYSIOLOGY OF URINE FORMATION

The cells of the body produce nitrogenous wastes which are transported via blood to the kidneys. Here they are converted into urine by three processes: 1) Ultrafiltration (Glomerular Filtration), 2) Tubular Reabsorption, and 3) Tubular Secretion.

Ultrafiltration is a passive process involving hydrostatic pressure to force fluids and solutes across a membrane. The glomerulus filters wastes more efficiently because its filtration membrane has a larger surface area and is thousand times more permeable to water and solutes compared to other capillary beds.

The glomerular capsule’s inner part is made up of three layers (collectively called the filtration membrane) acting as barriers or filters:

  1. Fenestrated Glomerular Capillary Endothelial Cells: Have perforations (gaps of 70-100 nm); leakier than other capillaries; prevent exit of blood cells and platelets.
  2. Basal Lamina: Thin layer of extracellular matrix gel; collagen fibres form a meshwork; prevents entry of substances >8 nm diameter; negatively charged collagen repels negatively charged plasma proteins.
  3. Podocytes: Form visceral layer of glomerular capsule; finger-like pedicels interlock to form narrow filtration slits; allow entry of substances <6-7 nm diameter.

NFP is the total pressure gradient which drives water across the filtration membrane to reach the capsular space. Three main forces act on the glomerular bed:

  • Glomerular Hydrostatic Pressure (GHP): Blood pressure in glomerular capillaries (≈ 50 mmHg) – promotes filtration
  • Capsular Hydrostatic Pressure (CHP): Pressure exerted by fluid in capsular space (≈ 10 mmHg) – opposes filtration
  • Glomerular Colloid Osmotic Pressure (GCOP): Due to plasma proteins (≈ 30 mmHg) – opposes filtration

NFP = GHP – (GCOP + CHP) = 50 – (30 + 10) = 10 mmHg

GFR is the amount of filtrate produced by both kidneys per minute. Normal GFR ≈ 125 ml/min. Kidneys form around 180 litres of filtrate per day. Since the body contains only 3 litres of plasma, the kidneys filter the entire plasma volume about 60 times a day.

Tubular reabsorption is a selective transepithelial process that begins when the filtrate enters the proximal tubules. Reabsorbed substances enter the blood via two routes:

  • Transcellular Route: Substances pass through luminal membrane → diffuse across cytosol → pass through basolateral membrane → enter peritubular capillaries
  • Paracellular Route: Movement of substances between tubule cells through tight junctions (leaky in proximal nephron for Ca²⁺, Mg²⁺, K⁺, Na⁺)

Tubular reabsorption is either passive (ATP not required) or active (requires ATP directly or indirectly) depending on the substances being transported.

Tubular secretion clears the plasma of unwanted substances (reverse of reabsorption). H⁺, K⁺, NH₄⁺, creatinine, and certain organic acids are either synthesised in tubule cells and secreted, or reach the filtrate by passing through tubule cells from peritubular capillaries. The PCT is the major secretion site, but cortical parts of collecting ducts are also active.

  1. Disposing of Substances: Removes drugs and metabolites tightly bound to plasma proteins
  2. Eliminating Undesirable Substances: Removes urea and uric acid (nitrogenous wastes) – 40-50% of urea in filtrate is excreted
  3. Eliminating Excess K⁺ Ions: Aldosterone-driven active tubular secretion into DCT and collecting ducts
  4. Controlling Blood pH:
    • Low blood pH (acidic): Tubular cells secrete more H⁺, produce more HCO₃⁻ → raises blood pH
    • High blood pH (alkaline): Cl⁻ ions are reabsorbed and excreted via urine
ProcessLocationDirectionKey Feature
Glomerular FiltrationRenal CorpuscleBlood → Bowman’s CapsulePassive; driven by hydrostatic pressure
Tubular ReabsorptionRenal Tubules (mainly PCT)Lumen → BloodSelective; active or passive
Tubular SecretionRenal Tubules (PCT, DCT, Collecting Duct)Blood → LumenRemoves wastes; controls pH and K⁺
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