Excretion 2

• Major functions of the kidney


  • Regulate body fluid volume and osmolality (e.g. plasma)
  • Electrolyte balance (e.g. sodium)
  • Formation of urine and resulting excretion of metabolic waste products and toxins
  • Acid-base balance
• Kidney basic structure


  • Ureter
  • Cortex
  • Medulla
  • Renal Pyramids
  • Renal Pelvis
• Vertebrate kidneys form urine, remainder of urinary system is ductwork that carries urine to bladder or hindgut
• Nephron


  Basic functional unit of kidney
• Glomerular Filtration


  1. Glomerulus and Bowman's capsule perform ultrafiltration

  2. Proximal and distal tubules perform specific reabsorption and secretion

  3. Loop of Henle and collecting duct perform osmoconcentration (only in birds and mammals)
• Every minute ~20% of our blood passes into the kidneys
• Glomerular membrane

  • 3 layers form fine molecular sieve: Glomerular capillary wall, Basement membrane, Inner layer of Bowman's capsule (podocyte cells)
• Glomerular capillary blood pressure is the major force that causes glomerular filtration
• Changes in glomerular filtration rate (GFR) result primarily from changes in glomerular capillary pressure
• Juxtaglomerular Apparatus (JGA)


  This structure is involved in regulation of GFR
• Tubular reabsorption


  1. Involves passive and active transport

  2. Tremendous amounts involved, highly selective and variable process

  3. Na+ reabsorption vital for reabsorption of Cl-, glucose, amino acids and water

  4. Na+ reabsorption regulates of osmolality

  5. Kidneys regulate phopshate but not glucose reabsorption

  6. Waste products (except some urea) not reabsorbed
• Humans: filter ~180 litres of blood per day, ~99% of reabsorbed, ~1.5 litres of urine produced
• Proximal Tubule


  Most of the reabsorption, also major site for secretion (with the exception of K+)
• Distal tubule and collecting ducts


  Determine final amounts of water, Na+, K+ and H+ excreted in urine (i.e. "fine tuning")
• Renin-angiotensin-aldosterone system (RAAS)


  Stimulates Na+ reabsorption in distal tubules and collecting ducts, elevates blood pressure, stimulates thirst and hunger
• Atrial and brain natriuretic peptides (ANP, BNP)


  Antagonize the RAAS, inhibiting: Na+ reabsorption, reducing blood pressure
• Renin-Angiotensin System


  Angiotensinogen from liver, Renin from JGA, Converting enzyme in lung, Angiotensin I, Angiotensin II, Aldosterone, Na+ and H2O retention, Increased blood volume and pressure
• Tubular secretion


  H+ secretion is important in acid-base balance, K+ secretion is controlled by aldosterone, Organic anion and cation secretion helps eliminate foreign compounds from the body, Plasma clearance, the volume of plasma cleared of a particular substance per minute, is used to characterize secretion
• Why does colour of urine change?

  Diluted (Contain lots of water, e.g. Winter day), Concentrated (Little water, smaller volume, e.g. Hot summer's day)
• Osmoconcentration


  Medullary vertical osmotic gradient is established by countercurrent multiplication with the thick ascending limb of the loop pumping NaCl out without water following, Interstitial NaCl build up draws water out of descending limb
• Vertical Osmotic gradient in the human renal medulla: Cortex: 300 mOsm, Medulla: 1200 mOsm
• Countercurrent exchange within the vasa recta blood vessels


  Conserves the medullary vertical osmotic gradient
• Concentration of urine


  Fluid passing down CD meets ever increasing medullary concentrations, therefore water removed by osmosis, water permeability of CD increases with presence of anti-diuretic hormone (vasopressin)
• Brain


  Measures relative water concentration of blood plasma (osmoreceptors in hypothalamus), brain secretes vasopressin from posterior pituitary gland in response to a decrease in body water content
• Vasopressin


  In dehydration, triggers insertion of aquaporin water channels (AQP2) into epithelial membrane of collecting duct cells, water drawn out to conserve water (anti-diuresis), In overhydration, no vasopressin released, so water retained in collecting duct lumen, so water is then excreted from the body in urine (diuresis)
• Renal collecting duct cell membrane water permeability


  No vasopressin present: Low water permeability, Vasopressin present: High water permeability, Water channels inserted into cell membrane
• Vasopressin (ADH) regulation


  Vasopressin causes AQP2 to move to the apical membrane of collecting duct cells
• Different osmoconcentrating abilities among species depend on nephron anatomy and metabolic rates, Animals with long loops and high metabolic rates capable of highest levels of osmoconcentration
• Functions of nephron regions

  • Proximal tubule: Most water reabsorbed, Most salts reabsorbed
  • Descending limb of loop of Henle: A little water reabsorbed, No salts reabsorbed
  • Ascending limb of loop of Henle: No water reabsorbed, Some salts reabsorbed
  • Distal tubule: Some water reabsorbed, Some salts reabsorbed
  • Collecting Duct: A little water reabsorbed (VARIABLE), No salts reabsorbed
• The Inner Medulla Mystery


  1. Proposed answer: Passive urea recycling in the inner medulla contributes to hypertonicity (and prevents urea diuresis)

  2. Problem: Countercurrent multiplication process nicely explains outer medulla gradients, but does not fully explain high osmolality of inner medulla
• Renal Urea Transporters


  UT-A in CD cells, IMCD urea permeability controlled by vasopressin
• UT-A knockout mice: lower urea levels in medulla BUT still have high levels of NaCl
• Other suggested explanations for the Inner Medulla Mystery: "Pelvic pumping" enhances concentration, external osmolytes (not yet tested), 3 counter-current systems in inner medulla