Proximal convoluted tubule

• K+ transport

  1. Passive 60-70% movement - solvent drag in early PCT

  2. Primary active transport of K+ with Na+ in PCT

  3. Secondary active transport of K+ with Na+ and Cl- in Loop of Henle (NKCC2)
• Urea

  • A breakdown product of amino acid metabolism
  • Filtered at glomerulus
  • Freely secreted and absorbed by tubular membranes
  • Passively reabsorbed (& by solvent drag in PCT) & by diffusion in medullary collecting duct (MCD)
  • As water diffuses across PCT membrane into interstitial fluid this increases conc. of urea in tubular fluid
  • So urea moves down conc. gradient back into plasma in peritubular capillaries
  • Hence urea transport is dependent on water transport
  • Secreted in LOH via urea transporter (UT2)
  • UT1-4 UTA1 &3 in IMCD
• Na+ reabsorption mechanisms

  1. Na+/K+/Cl- symport on apical membrane

  2. Na+ channels (ENaC)

  3. Na+/Cl- cotransporters
• Symptoms of glucosuria

  • Electrolyte imbalance
  • Pruritus (itching)
  • Low BP
  • Polyuria
• Fanconi's syndrome

  • Mutation in genes encoding for specific transporters in nephron
  • Damage to transporters in PCT
  • Suffers excess loss of bicarbonate, glucose, AA, phosphates
  • Polyuria (osmotic diuresis)
  • Osteomalacia/rickets
• Familiar Renal Glucosuria

  • Genetic disorder
  • Mutation in Na+/glucose active transport mechanism in the renal PCT
  • Inadequate reabsorption of glucose in PCT
  • Glucose lost in urine
  • Very different to Diabetes Mellitus where transporter saturated
• Describe body fluid distribution

  There is 32-40L of fluid in the body, which accounts for around 60-70% of body weight.

  • Intracellular fluid: 40%
  • Extracellular fluid:
  • Interstitial fluid: 15%
  • Plasma: 5%

  Concentration of solutes in the body fluid= 290-300 mOsmol
• Outline the function of the kidneys

  1. Glomerular filtration: blood is filtered to produce plasma like filtrate
  2. Tubular reabsorption: removal of useful solutes from the filtrate to be reabsorbed into the blood
  3. Tubular secretion: removal of additional solutes from the blood into the filtrate
  4. Conservation of water: removal of water from the filtrate and return to the blood
• Describe the function and structure of the PCT

  Long length to maximise SA, as well as microvilli and mitochondria for active transport. It is responsible for bulk reabsorption of a great variety of substances by osmosis, water, or active transport, sodium, glucose, amino acids and urea. It is also responsible for tubular secretion, where tubular cells secrete substances, such as H+ ions, into the filtrate in order to maintain the balance of other body fluids. As you move down the PCT, the lumen increases and there are less microvilli. As well as this there are less S1 cells and more S3 cells.
• What is solvent drag?

  This describes the diffusion of water molecules, driven by osmotic pressure, which carries solute particles along with it. Water diffuses through aquaporins in the cell membrane or between cells. The most common channel in aquaporin 1.
• Describe a uniport

  This is a type of transporter where one substance moves down its concentration gradient in one direction. It allows the movement, via diffusion, of large polar molecules, e.g., glucose via GLUT2 on the basolateral membrane.
• Describe and cotransporter/symporter

  This is a transporter where more than one solute is moving in the same direction.
• Describe an antiporter/exchanger

  This is a transporter where more than one solute is moving in opposite directions
• Describe some examples of primary active transporters

  1. Na+ and K+ ATPase antiporter on the basolateral membrane
  2. H+ ATPase uniport on the apical membrane
  3. H+ K+ ATPase antiporter on the apical membrane

  
• Describe secondary active transport

  Movement of a substance against its concentration gradient by utilising the movement of another substance, usually Na+ moving down its concentration gradient. These can be symports, such as Na+/glucose SGLT-1, or antiporters such as Na+/H+.
• Draw a diagram showing the types of mediated transport

  Basolateral membrane: GLUT 1 and GLUT 2

  Apical membrane: SGLT 1 and SGLT 2

  
• Describe how glucose transport is compromised in diabetes mellitus

  In people with Diabetes Mellitus there is often saturation of SGLT1 and SGLT2 in the PCT apical membrane due to hyperglycaemia. This means that glucose remains in the urine, which is known as Glycosuria. Glucose will also draw in water from the filtrate, leading to dehydration and changes in GFR due to alteration of blood volume.
• Describe the action of SGLT2 inhibitors

  This is often utilised as a treatment for type II diabetes. These drugs, known as glifozins, can reduce glucose reabsorption in the PCT and reduce plasma glucose levels by blocking SGLT2 transporters. However, this produces side effects such as increased risk of UTI and poor renal function.
• Describe the action of OATS

  1. Alpha-ketoglutarate is pumped out of the cell across the basolateral membrane and into the plasma.
  2. This movement is coupled with the entering of organic anion into the cell.
  3. Organic anions can then leave the cell across the apical membrane.
• Describe HCO3- transport

  1. CO2 and H2O move passively into the cell
  2. Cytoplasmic enzyme carbonic anhydrase II and IV converts them into to H+ and HCO3-
  3. 90% HCO3- is reabsorbed across the basolateral membrane via NBCe1 and SCL26A6