Outline the problems that arise from kidney failure and discuss the use of renal dialysis and transplants for the treatment of kidney failure Kidney failure affects tens of thousands of people each year in the UK If one kidney fails, one can survive with one functioning kidney If both kidneys fail, death will result within about 2 weeks without medical treatment Death often results from build up of potassium ions... ... which causes heart failure

Filters blood under pressure Damaged by excessive pressure Adjusts pH of blood Adjusts water content of blood in response to ADH Selectively reabsorbs glucose, amino acids, vitamins, sodium and chloride ions Reabsorbs water NOTE: regulation of water balance helps regulate blood volume which helps regulate blood pressure

Chronic kidney failure Progressive, long term kidney failure – takes place over a number of years Possible causes: - Bacterial infection of pelvis and surrounding tissue - Nephritis: inflammation of glomeruli due to antibodies to other infections attacking tissue - Damage due to high blood pressure - Damage due to obstruction of ureter, bladder or urethra - Diabetes mellitus (sugar diabetes) - Atherosclerosis – reduces blood supply to kidney

Chronic kidney failure Nephrons are progressively destroyed, leading to: - Reduced quantity of urine - Dilute urine - Dehydration - Salt imbalance - Severe high blood pressure - Coma and convulsions

Acute kidney failure Relatively sudden failure of kidney Possible causes: - Loss of blood supply to kidney... ... possibly as a result of blood loss in accident ... ... heart failure... ... or toxic chemicals - Severe bacterial infection or nephritis - Physical damage to kidney - Obstruction of ureters, bladder or kidney

Acute kidney failure Leads to: - Little or no urine produced - Accumulation of nitrogenous waste in blood - Salt imbalance - Pain Often reversible if treated QUICKLY

‘Renal Dialysis’ or ‘Haemodialysis’ Used to remove waste products such as urea, excess ions such as potassium and excess water from the blood when the kidneys are incapable of doing this

Blood is passed diverted through the dialysis machine. The dialyser contains a semi-permeable membrane made of cellulose acetate or nitrate (e.g. Visking tubing) Blood flows on one side of the dialysis membrane and a dialysis fluid flows on the other side Waste materials and excess salts and water diffuse across the dialysis membrane into the dialysis fluid.

Trap for air bubbles Reservoir of fresh dialysis fluid Used From patient circulation To patient Dialyser Heater

The dialysing fluid is formulated to ensure that only waste products and excess substances diffuse across the membrane Note: for diffusion to occur, there must be a concentration gradient for the substance concerned to diffuse down The dialysing fluid contains no urea or other excretory products, ensuring that these diffuse rapidly A countercurrent system ensures that the concentration of urea etc is always higher on the blood side of the dialysis membrane

The concentration of glucose, mineral ions and other useful The concentration of glucose, mineral ions and other useful substances is the same in the dialysing fluid as in normal blood plasma These substances will only diffuse across into the dialysis fluid if their levels in the plasma are above normal levels The dialysing fluid also contains dextran – a polysaccharide which cannot pass through the dialysing membrane The level of dextran ensures that the water potential of the dialysing fluid is the same as normal plasma If the plasma contains excess water, this will move into the dialysing fluid by osmosis.

If the blood and dialysing fluid flow in the same direction (concurrent flow), then the concentration gradient between adjacent regions of blood and dialysing fluid will drop as diffusion takes place along the length of the dialysing membrane 100 70 45 50 30 Flow Diffusion Gradient This will cause the rate of diffusion to slow as we move along the length of the dialysing membrane

In a counter-current system, the concentration gradient is maintained along the length of the dialysis membrane 100 80 60 40 20 Flow Diffusion Gradient

Kidney transplants First kidney transplants were performed in 1960’s ~1800 transplants are performed each year in UK Number of transplants is limited by: availability of donors availability of good tissue match with patient Kidney transplants have high survival rates Tissue rejection is prevented with use of drugs such as cyclosporin A which damp the immune response As you only need one kidney, close relatives can act as donors (reduces risk of rejection)

Kidney transplants Transplants are cheaper than dialysis - Cost of dialysis was ~£20 000/year in mid 90’s - Post-transplant drug therapy cost ~£3000/year Quality of life for patient is better if procedure is successful