Kidneys

• Kidney


  Mammalian organ that regulates the composition of the blood by removing waste products and helping to maintain the volume of water and concentration of mineral ions
• Ultrafiltration


  1. Occurs between the glomerulus and the Bowman's capsule

  2. High blood/hydrostatic pressure in the glomerulus capillaries forces water and small solute molecules out of the blood plasma into the Bowman's capsule

  3. Only molecules with a relative molecular mass of < 69,000 pass through

  4. Blood cells and most proteins are too large to be filtered out of the blood plasma, and so they remain in the glomerular capillaries
• Glomerulus and capsule filter system


  • Filtrate must cross 3 barriers before entering the Bowman's capsule: capillary wall of the glomerular capillaries, basement membrane of the glomerular capillary, podocytes - specialised epithelial cells forming the wall of the Bowman's capsule
• Glomerular filtration rate is around 180 dm3 per day in humans, while the volume of urine produced is only around 1.5 to 2.0 dm3 per day
• Selective reabsorption


  1. Occurs in the proximal convoluted tubule

  2. Main molecules selectively re-absorbed are: all glucose, all amino acids, 80-85% of the water, some ions, a little urea

  3. Reabsorption occurs from the filtrate in the proximal convoluted tubule into the blood plasma in the surrounding capillaries
• Adaptations of the proximal convoluted tubule for reabsorption

  • Long to increase surface area, microvilli on the luminal membrane to increase surface area, tight junctions between cells to ensure movement occurs through cells not between them, one cell thick wall for short reabsorption distance, surrounded by capillaries for short reabsorption distance, many mitochondria to provide ATP for active transport, many protein carriers/channels in the epithelial membranes for transport, large RER network to synthesise protein carriers and channels
• Descending limb of loop of Henle

  Water leaves by osmosis, moving from a higher water potential (in the filtrate) to a lower water potential (in the medulla), Na+ and Cl- ions diffuse from the medulla into the filtrate, as water leaves the filtrate and ions diffuse in, the filtrate becomes more concentrated/water potential decreases
• Ascending limb of loop of Henle

  In the lower, thinner region, Na+ and Cl- ions diffuse out, in the upper, thicker region, Na+ and Cl- ions are actively transported out of the filtrate into the medulla, ascending limb wall is impermeable to water (no aquaporins), so water cannot leave, as ions leave the filtrate and water cannot follow, the filtrate becomes less concentrated/water potential increases
• Counter-current multiplier system

  The descending limb and ascending limb arrangement, the changes that occur in the filtrate concentration as it moves through the loop of Henle results in a decreasing water potential going down the medulla, the longer the Loop of Henle, the greater the countercurrent multiplier effect and the lower the water potential of the medulla can become
• Longer loops of Henle

  More water can be reabsorbed as the medulla can be made even more salty/lower water potential
• Osmoreceptors


  Cells in the hypothalamus of the brain that can detect a fall in water potential and trigger the release of antidiuretic hormone (ADH)
• ADH


  Binds to receptors on the cell surface membranes of the cells in the collecting ducts, causes insertion of more aquaporins into the luminal cell surface membranes, making collecting duct cells more permeable to water, more water is reabsorbed by osmosis from the collecting duct into the medulla, and then the blood plasma
• A lower volume of more concentrated urine is produced
• ADH


  Cells in the hypothalamus of the brain contain osmoreceptors that are able to detect a fall in water potential. The osmoreceptors work by losing water through osmosis when the water potential of the blood falls. This triggers the neurosecretory cells in the hypothalamus to produce ADH, which is secreted into blood capillaries.
• ADH action


  1. ADH binds to receptors on the cell surface membranes of the cells in the collecting ducts

  2. Causes insertion of more aquaporins into the luminal cell surface membranes

  3. Making collecting duct cells more permeable to water

  4. More water is reabsorbed by osmosis from the collecting duct into the medulla, and then the blood plasma

  5. A lower volume of more concentrated urine helps the blood plasma water potential to return to a normal level

  6. ADH is slowly broken down (half life of 20 mins) to reduce the stimulation of the collecting ducts
• Urea reabsorption from the Collecting Duct


  As filtrate moves down the collecting duct and water is re-absorbed the urea concentration increases. The steep concentration gradient created means some urea is re-absorbed from the filtrate into the medulla. This helps lower the medulla water potential aiding re-absorption of water from the collecting duct.
• If the water potential of the blood is too high

  • Osmoreceptors in the hypothalamus are not stimulated
  • No nerve impulses are sent to the posterior pituitary gland
  • No ADH released
  • Aquaporins are moved out of the luminal membranes of the collecting duct cells
  • Collecting duct cells are no longer permeable to water
  • The filtrate flows along collecting duct but loses no water and is very dilute
  • A large volume of dilute urine is produced
  • This flows from the kidneys, through the ureters and into the bladder
• Distal convoluted tubule (DCT)

  The distal convoluted tubule (DCT) can reabsorb mineral ions in order to maintain the balance of mineral ions in the blood. The concentration of Na+ ions is monitored and if it falls below a set point the cells in the outer part of the adrenal gland secrete the hormone aldosterone. Aldosterone switches on genes that produce carrier proteins for Na+. These carriers pump sodium ions out of the filtrate so that can be reabsorbed back into the bloodstream.
• Kidney failure may be acute (more likely to be reversible) or chronic.
• Testing for kidney disease


  We can test the blood for levels of the waste product creatine. This gives us an estimate of the glomerular filtration rate (GFR given in cm3/min). A higher concentration of creatine in the blood indicates a lower GFR which suggest a problem with the kidneys. However, GFR does decrease with age, even in healthy individuals, and creatine concentrations are higher in men than women.
• We can survive fine with only one functioning kidney. However, when both are damaged and appropriate treatment is lacking, the body cannot control levels of water and ions, blood pressure will increase, waste products such as urea build up, bones may weaken, joint pain may occur, and anaemia may develop.
• Kidney failure treatments


  • Dialysis
  • Kidney transplant
• Haemodialysis


  Dialysis involves separating large and small molecules using a partially permeable membrane. Haemodialysis involves regular visits to the hospital which take several hours each time. It also places restrictions on what patients eat in order to avoid excessive build up of urea between dialysis sessions.
• Peritoneal dialysis


  An alternative form of dialysis in which a catheter is placed into the abdominal cavity and the dialysate is pumped into the space. Dialysis occurs across the peritoneum (lining of the abdomen). This is left for several hours and then the fluid is drained and discarded.
• Kidney transplant


  The transplanted organ may be from a living donor or may be taken from a donor shortly after death. The new kidney must be connected to the blood supply and to the bladder to enable it to function. A transplant can drastically improve patients lives, however the immune system would react against the new organ unless immunosupressant drugs are given.
• Presence of any glucose in the urine suggests a failure in homeostatic control of glucose levels and/or kidney failure.
• Pregnancy testing


  Urine samples can be used in pregnancy testing. Pregnancy testing sticks contain monoclonal antibody molecules that are specific to a hormone produced during pregnancy (human chorionic gonadotropin, hCG) that becomes present in the mother's urine. The antibodies in the testing sticks all originate from a single clone of B lymphocyte cells that all produce the same antibody specific to hCG, which minimises the chances of false test results.
• Testing athletes


  Athletes may be tested for drugs such as anabolic steroids (increase muscle mass) which may improve their performance e.g. by speeding up recovery or increasing endurance.
• Gas Chromatography


  Urine sample vaporised in the presence of gaseous solvent and passed through machine. Each substance dissolves differently = Retention Time. Substance is absorbed into the lining and analysed to create a chromatogram. Compared to standard samples of drugs.