Urinary system

C cortex Cp capsule H hilum M medulla P papilla U ureter

Renal failure occurs for a variety of reasons and may be acute or chronic. Irreversible severe renal failure is inevitably fatal unless some form of renal replacement therapy is undertaken. Current options for renal replacement therapy include renal dialysis and renal transplantation. Dialysis may take the form of haemodialysis or, less commonly, peritoneal dialysis. Renal transplantation requires a donor, which can often involve a long wait until a suitable HLA-compatible donor is found. Those individuals lucky enough to have a compatible and willing family member are able to receive a donated kidney from them. This highlights the inbuilt redundancy of the kidneys whereby an individual can survive and be perfectly healthy with only one kidney. Stem cell research may in future provide a third option for renal replacement, the possibility of growing one’s own perfectly matched new kidney (or heart or pancreas) from one’s own stem cells.

AA arcuate artery Ai interlobar artery AV arcuate vein C calyx Cx cortex G glomerulus IA interlobular artery MR medullary ray P renal pelvis RC renal corpuscle RP renal papilla T tubule U ureter V interlobular vein

A afferent arteriole BC Bowman’s capsule BS Bowman’s space C glomerular capillary E endothelial cell GBM glomerular basement membrane I interstitium M mesangium N mesangial cell nucleus P podocyte PCT proximal convoluted tubule S parietal epithelial cell

AA afferent arteriole BS Bowman’s space EA efferent arteriole G glomerulus IA interlobular artery N podocyte nucleus P ₁ podocyte primary process P ₂ podocyte secondary process RT renal tubule

BC Bowman’s capsule BM glomular basement membrane BS Bowman’s space C capillary loop E endothelial cell F fenestration FS filtration slit IPS interpodocyte space M mesangial cell MM mesangial matrix P podocyte P ₁ podocyte primary process P ₂ podocyte secondary foot process SPS subpodocyte space

Diabetic nephropathy is the most common cause of renal failure in affluent countries . The incidence of type 2 diabetes is increasing, an increase that is felt to be largely due to changing lifestyles, with increasing obesity and decreasing exercise, although there is little doubt that genetic factors are also important. Usually one of the earliest signs of diabetic nephropathy is proteinuria, which may eventually progress to the nephrotic syndrome and progressive chronic renal failure. The microscopic features in these cases include thickening of the mesangial basement membrane and an increase in mesangial matrix, often called diabetic glomerulosclerosis. In normal glomeruli, the balance between deposition of new and removal of old mesangial matrix is very tightly controlled. Recent research is beginning to tease out the mechanisms underlying these clinical features, including chemical mediators such as transforming growth factor β (TGF-β) that induce increased deposition of mesangial matrix in response to high glucose concentrations. This mesangial matrix has a different composition to normal matrix, including increased amounts of type I and type III collagen which are not easily removed from the glomerulus. However, other factors, including direct podocyte injury and changes in the slit pore membrane, also contribute to the characteristic proteinuria that precedes frank renal failure.

Diabetics also tend to suffer from vascular disease, hypertension and increased infections in the kidney, and all of these tend to contribute to the development of end-stage renal failure .

BB brush border BM basement membrane C peritubular capillaries CP mesangial cell cytoplasmic process DCT distal convoluted tubule E endothelial cell J cell junction L glomerular capillary lumen PCT proximal convoluted tubule MC mesangial cell MM mesangial matrix P ₁ podocyte primary process P ₂ podocyte secondary foot process SPS subpodocyte space

Damage to the renal tubules is a fairly common cause of acute renal failure. Acute tubular necrosis usually occurs due to a sudden drop in the blood supply to the kidney, for example due to severe dehydration or massive blood loss. The cells of the renal tubules are highly metabolically active and so they are very susceptible to damage when the blood supply is compromised. As noted above, this is particularly so for the cells of the proximal convoluted tubule as they have a very high oxygen requirement.

The tubular epithelial cells will often recover if the underlying cause is treated and the patient is supported effectively during the acute phase of their illness. Often, during the recovery phase, the patient will produce very large volumes of dilute urine ( polyuria ), highlighting the key role of the tubular epithelial cells in reabsorbing water from the glomerular ultrafiltrate . Careful management of fluid balance is critical during recovery.

BM basement membrane BM _E basement membrane of endothelium Cap capillary E endothelium J junctional complex L lysosome M mitochondrion Mv microvilli P cell process S supporting tissue V pinocytotic vesicle

AA afferent arteriole DCT distal convoluted tubule J juxtaglomerular cell L lacis cell MD macula densa

Hypertension is a common condition in middle-aged and elderly persons. Most cases are considered to be idiopathic (which simply means that the mechanism has not yet been elucidated). However, there are certainly genetic factors as well as lifestyle components underlying many, if not most, cases. A much smaller proportion of hypertensive patients, especially younger patients, have hypertension associated with renal disease. Many different types of renal disease may lead to hypertension; a classic example is the acute hypertension seen in patients with post-infectious glomerulonephritis. Many other chronic renal conditions, including diabetic nephropathy, IgA nephropathy and a range of other common conditions lead to secondary hypertension.

Conversely, hypertension can also lead to renal failure. The classic example of this is patients with accelerated hypertension who have acute renal failure with classic vascular changes in their renal biopsy at presentation. However, chronic untreated lower-level hypertension also typically leads to chronic renal damage in a pattern sometimes called ‘benign nephrosclerosis’, a misleading name as it can lead to chronic renal failure which may require renal replacement therapy.

A thick ascending limb of loop of Henle BM tubular basement membrane CD collecting duct CT collecting tubule IC intercalated cell S supporting tissue T thin limb of loop of Henle V vasa recta

BL basal lamina BM basement membrane C collagen fibrils CT collecting tubule D lipid droplet H loop of Henle L leukocyte N nucleus of interstitial medullary cell P cytoplasmic process of interstitial medullary cell S supporting tissue V vasa recta

A adventitia C circular muscle layer DB duct of Bellini E transitional epithelium IL inner longitudinal muscle layer of bladder L longitudinal muscle layer of ureter LP lamina propria OL outer longitudinal muscle layer of bladder PCS pelvicalyceal space SM smooth muscle U ureter Um umbrella cell V blood vessel