Glomerulus Health Dictionary

Each kidney comprises over a million of these microscopic units which regulate and control the formation of URINE. A tuft of capillaries invaginates the Bowmans capsule, which is the blind-ending tube (GLOMERULUS) of each nephron. Plasma is ?ltered out of blood and through the Bowmans capsule into the renal tubule. As the ?ltrate passes along the tubule, most of the water and electrolytes are reabsorbed. The composition is regulated with the retention or addition of certain molecules (e.g. urea, drugs, etc.). The tubules eventually empty the ?ltrate, which by now is urine, into the renal pelvis from where it ?ows down the ureters into the bladder. (See KIDNEYS.)... nephron

Each of the two KIDNEYS ?lters a large volume of blood – 25 per cent of cardiac output, or around 1,300 ml – through its two million glomeruli (see GLOMERULUS) every minute. The glomeruli ?lter out cell, protein, and fat-free ?uid which, after reabsorption of certain chemicals, is excreted as urine. The rate of this ultra?ltration process, which in health is remarkably constant, is called the glomerular ?ltration rate (GFR). Each day nearly 180 litres of water plus some small molecular-weight constituents of blood are ?ltrated. The GFR is thus an indicator of kidney function. The most widely used measurement is CREATININE clearance and this is assessed by measuring the amount of creatinine in a 24-hour sample of urine and the amount of creatinine in the plasma; a formula is applied that gives the GFR.... glomerular filtration rate (gfr)

Diseases affecting the kidneys can be broadly classi?ed into congenital and genetic disorders; autoimmune disorders; malfunctions caused by impaired blood supply; infections; metabolic disorders; and tumours of the kidney. Outside factors may cause functional disturbances – for example, obstruction in the urinary tract preventing normal urinary ?ow may result in hydronephrosis (see below), and the CRUSH SYNDROME, which releases proteins into the blood as a result of seriously damaged muscles (rhabdomyolosis), can result in impaired kidney function. Another outside factor, medicinal drugs, can also be hazardous to the kidney. Large quantities of ANALGESICS taken over a long time damage the kidneys and acute tubular NECROSIS can result from certain antibiotics.

K

Diagram of glomerulus (Malpighian corpuscle).

Fortunately the body has two kidneys and, as most people can survive on one, there is a good ‘functional reserve’ of kidney tissue.

Symptoms Many patients with kidney disorders do not have any symptoms, even when the condition is quite advanced. However,

others experience loin pain associated with obstruction (renal colic) or due to infection; fevers; swelling (oedema), usually of the legs but occasionally including the face and arms; blood in the urine (haematuria); and excess quantities of urine (polyuria), including at night (nocturia), due to failure of normal mechanisms in the kidney for concentrating urine. Patients with chronic renal failure often have very di?use symptoms including nausea and vomiting, tiredness due to ANAEMIA, shortness of breath, skin irritation, pins and needles (paraesthesia) due to damage of the peripheral nerves (peripheral neuropathy), and eventually (rarely seen nowadays) clouding of consciousness and death.

Signs of kidney disease include loin tenderness, enlarged kidneys, signs of ?uid retention, high blood pressure and, in patients with end-stage renal failure, pallor, pigmentation and a variety of neurological signs including absent re?exes, reduced sensation, and a coarse ?apping tremor (asterixis) due to severe disturbance of the body’s normal metabolism.

Renal failure Serious kidney disease may lead to impairment or failure of the kidney’s ability to ?lter waste products from the blood and excrete them in the urine – a process that controls the body’s water and salt balance and helps to maintain a stable blood pressure. Failure of this process causes URAEMIA – an increase in urea and other metabolic waste products – as well as other metabolic upsets in the blood and tissues, all of which produce varying symptoms. Failure can be sudden or develop more slowly (chronic). In the former, function usually returns to normal once the underlying cause has been treated. Chronic failure, however, usually irreparably reduces or stops normal function.

Acute failure commonly results from physiological shock following a bad injury or major illness. Serious bleeding or burns can reduce blood volume and pressure to the point where blood-supply to the kidney is greatly reduced. Acute myocardial infarction (see HEART, DISEASES OF) or pancreatitis (see PANCREAS, DISORDERS OF) may produce a similar result. A mismatched blood transfusion can produce acute failure. Obstruction to the urine-?ow by a stone (calculus) in the urinary tract, a bladder tumour or an enlarged prostate can also cause acute renal failure, as can glomerulonephritis (see below) and the haemolytic-uraemia syndrome.

HYPERTENSION, DIABETES MELLITUS, polycystic kidney disease (see below) or AMYLOIDOSIS are among conditions that cause chronic renal failure. Others include stone, tumour, prostatic enlargement and overuse of analgesic drugs. Chronic failure may eventually lead to end-stage renal failure, a life-threatening situation that will need DIALYSIS or a renal transplant (see TRANSPLANTATION).

Familial renal disorders include autosomal dominant inherited polycystic kidney disease and sex-linked familial nephropathy. Polycystic kidney disease is an important cause of renal failure in the UK. Patients, usually aged 30–50, present with HAEMATURIA, loin or abdominal discomfort or, rarely, urinary-tract infection, hypertension and enlarged kidneys. Diagnosis is based on ultrasound examination of the abdomen. Complications include renal failure, hepatic cysts and, rarely, SUBARACHNOID HAEMORRHAGE. No speci?c treatment is available. Familial nephropathy occurs more often in boys than in girls and commonly presents as Alport’s syndrome (familial nephritis with nerve DEAFNESS) with PROTEINURIA, haematuria, progressing to renal failure and deafness. The cause of the disease lies in an absence of a speci?c ANTIGEN in a part of the glomerulus. The treatment is conservative, with most patients eventually requiring dialysis or transplantation.

Acute glomerulonephritis is an immune-complex disorder due to entrapment within glomerular capillaries of ANTIGEN (usually derived from B haemolytic streptococci – see STREPTOCOCCUS) antibody complexes initiating an acute in?ammatory response (see IMMUNITY). The disease affects children and young adults, and classically presents with a sore throat followed two weeks later by a fall in urine output (oliguria), haematuria, hypertension and mildly abnormal renal function. The disease is self-limiting with 90 per cent of patients spontaneously recovering. Treatment consists of control of blood pressure, reduced ?uid and salt intake, and occasional DIURETICS and ANTIBIOTICS.

Chronic glomerulonephritis is also due to immunological renal problems and is also classi?ed by taking a renal biopsy. It may be subdivided into various histological varieties as determined by renal biospy. Proteinuria of various degrees is present in all these conditions but the clinical presentations vary, as do their treatments. Some resolve spontaneously; others are treated with steroids or even the cytotoxic drug CYCLOPHOSPHAMIDE or the immunosuppressant cyclosporin. Prognoses are generally satisfactory but some patients may require renal dialysis or kidney transplantation – an operation with a good success rate.

Hydronephrosis A chronic disease in which the kidney becomes greatly distended with ?uid. It is caused by obstruction to the ?ow of urine at the pelvi-ureteric junction (see KIDNEYS – Structure). If the ureter is obstructed, the ureter proximal to the obstruction will dilate and pressure will be transmitted back to the kidney to cause hydronephrosis. Obstruction may occur at the bladder neck or in the urethra itself. Enlargement of the prostate is a common cause of bladder-neck obstruction; this would give rise to hypertrophy of the bladder muscle and both dilatation of the ureter and hydronephrosis. If the obstruction is not relieved, progressive destruction of renal tissue will occur. As a result of the stagnation of the urine, infection is probable and CYSTITIS and PYELONEPHRITIS may occur.

Impaired blood supply may be the outcome of diabetes mellitus and physiological shock, which lowers the blood pressure, also affecting the blood supply. The result can be acute tubular necrosis. POLYARTERITIS NODOSA and SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) may damage the large blood vessels in the kidney. Treatment is of the underlying condition.

Infection of the kidney is called pyelonephritis, a key predisposing factor being obstruction of urine ?ow through the urinary tract. This causes stagnation and provides a fertile ground for bacterial growth. Acute pyelonephritis is more common in women, especially during pregnancy when bladder infection (CYSTITIS) spreads up the ureters to the kidney. Symptoms are fever, malaise and backache. Antibiotics and high ?uid intake are the most e?ective treatment. Chronic pyelonephritis may start in childhood as a result of congenital deformities that permit urine to ?ow up from the bladder to the kidney (re?ux). Persistent re?ux leads to recurrent infections causing permanent damage to the kidney. Specialist investigations are usually required as possible complications include hypertension and kidney failure.

Tumours of the kidney are fortunately rare. Non-malignant ones commonly do not cause symptoms, and even malignant tumours (renal cell carcinoma) may be asymptomatic for many years. As soon as symptoms appear – haematuria, back pain, nausea, malaise, sometimes secondary growths in the lungs, bones or liver, and weight loss – urgent treatment including surgery, radiotherapy and chemotherapy is necessary. This cancer occurs mostly in adults over 40 and has a hereditary element. The prognosis is not good unless diagnosed early. In young children a rare cancer called nephroblastoma (Wilm’s tumour) can occur; treatment is with surgery, radiotherapy and chemotherapy. It may grow to a substantial size before being diagnosed.

Cystinuria is an inherited metabolic defect in the renal tubular reabsorption of cystine, ornithine, lysine and arginine. Cystine precipitates in an alkaline urine to form cystine stones. Triple phosphate stones are associated with infection and may develop into a very large branching calculi (staghorn calculi). Stones present as renal or ureteric pain, or as an infection. Treatment has undergone considerable change with the introduction of MINIMALLY INVASIVE SURGERY (MIS) and the destruction of stone by sound waves (LITHOTRIPSY).... kidneys, diseases of

Nephrotic syndrome is one of PROTEINURIA, hypo-albuminaemia and gross OEDEMA. The primary cause is the leak of albumin (see ALBUMINS) through the GLOMERULUS. When this exceeds the liver’s ability to synthesise albumin, the plasma level falls and oedema results. The nephrotic syndrome is commonly the result of primary renal glomerular disease (see KIDNEYS, DISEASES OF – Glomerulonephritis). It may also be a result of metabolic diseases such as diabetic glomerular sclerosis and AMYLOIDOSIS. It may be the result of systemic autoimmune diseases such as SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) and POLYARTERITIS NODOSA. It may complicate malignant diseases such as MYELOMATOSIS and Hodgkin’s disease (see LYMPHOMA). It is sometimes caused by nephrotoxins such as gold or mercury and certain drugs, and it may be the result of certain infections such as MALARIA and CROHN’S DISEASE.... nephrotic syndrome

Inflammation of the glomeruli (see glomerulus), affecting both kidneys. Damage to the glomeruli hampers the removal of waste products, salt, and water from the bloodstream, which may cause serious complications.

Some types of glomerulonephritis are caused by immune complexes (components of the immune system produced in response to infection) becoming trapped in the glomeruli. The condition occurs in some autoimmune disorders. Infectious diseases such as malaria and schistosomiasis are important causes of glomerulonephritis in tropical countries.

Mild glomerulonephritis may produce no symptoms. Some sufferers experience a dull ache over the kidneys. The urine may become bloodstained. Loss of protein into the urine may cause oedema (see nephrotic syndrome). Hypertension is a potentially serious complication. Long-term glomerulonephritis is a common cause of chronic kidney failure.

Diagnosis involves kidney function tests, urinalysis, and kidney biopsy. Treatment depends on the cause and severity of the disease. Children with nephrotic syndrome usually respond to corticosteroid drugs. In adults, kidney failure can sometimes be prevented or delayed by drug treatment and dietary control to reduce the work of the kidneys.glomerulosclerosis Scarring caused by damage to the glomeruli (see glomerulus). Mild glomerulosclerosis occurs normally with age. Glomerulosclerosis may occur in some severe types of glomerulonephritis. It is also sometimes associated with diabetes mellitus, hypertension, AIDS, or intravenous drug abuse. glomerulus A filtering unit of the kidney that consists of a cluster of capillaries enclosed in a capsule and supplied with blood from the renal artery. Each glomerulus is a part of a larger filtering unit called a nephron. Filtered blood eventually leaves the kidney via the renal vein.

(See also glomerulonephritis.)... glomerulonephritis

A rare autoimmune disorder causing inflammation of the glomeruli in the kidney (see glomerulus) and the alveoli in the lungs, and anaemia. It is a serious disease; unless treated early it may lead to lifethreatening bleeding into the lungs and progressive kidney failure. The disease is most common in young men, but can develop at any age and in women. Sometimes, it responds to treatment with immunosuppressant drugs and plasmapheresis. People who have severe or repeated attacks require dialysis and, eventually, a kidney transplant.... goodpasture’s syndrome

the cup-shaped end of a *nephron, which encloses a knot of blood capillaries (glomerulus). It is the site of primary filtration of the blood into the kidney tubule. [Sir W. P. Bowman (1816–92), British physician]... bowman’s capsule

the part of a *nephron comprising the blood capillaries of the glomerulus and its surrounding Bowman’s capsule. [M. Malpighi (1628–94), Italian anatomist]... malpighian body

n. an epithelial cell in the *glomerulus that spreads over the capillary basement membrane and has branching tentacle-like processes that interdigitate with adjacent cells. The podocytes leave gaps or thin filtration slits. The slits are covered by slit diaphragms, which are composed of a number of cell-surface proteins including *nephrin, podocalyxin, and P-cadherin, which ensure that large molecules, such as albumin and gammaglobulin, are not filtered. Podocytes are damaged in *minimal change nephropathy and a major target of injury in *HIVAN.... podocyte

6.5 cm wide, 5 cm thick, and weighs around 140 grams.

Adult kidneys have a smooth exterior, enveloped by a tough ?brous coat that is bound to the kidney only by loose ?brous tissue and by a few blood vessels that pass between it and the kidney. The outer margin of the kidney is convex; the inner is concave with a deep depression, known as the hilum, where the vessels enter. The URETER, which conveys URINE to the URINARY BLADDER, is also joined at this point. The ureter is spread out into an expanded, funnel-like end, known as the pelvis, which further divides up into little funnels known as the calyces. A vertical section through a kidney (see diagram) shows two distinct layers: an outer one, about 4 mm thick, known as the cortex; and an inner one, the medulla, lying closer to the hilum. The medulla consists of around a dozen pyramids arranged side by side, with their base on the cortex and their apex projecting into the calyces of the ureter. The apex of each pyramid is studded with tiny holes, which are the openings of the microscopic uriniferous tubes.

In e?ect, each pyramid, taken together with the portion of cortex lying along its base, is an independent mini-kidney. About 20 small tubes are on the surface of each pyramid; these, if traced up into its substance, repeatedly subdivide so as to form bundles of convoluted tubules, known as medullary rays, passing up towards the cortex. One of these may be traced further back, ending, after a tortuous course, in a small rounded body: the Malpighian corpuscle or glomerulus (see diagram). Each glomerulus and its convoluted tubule is known as a nephron, which constitutes the functional unit of the kidney. Each kidney contains around a million nephrons.

After entering the kidney, the renal artery divides into branches, forming arches where the cortex and medulla join. Small vessels come o? these arches and run up through the cortex, giving o? small branches in each direction. These end in a tuft of capillaries, enclosed in Bowman’s capsule, which forms the end of the uriniferous tubules just described; capillaries with capsule constitute a glomerulus.

After circulating in the glomerulus, the blood leaves by a small vein, which again divides into capillaries on the walls of the uriniferous tubules. From these it is ?nally collected into the renal veins and then leaves the kidney. This double circulation (?rst through the glomerulus and then around the tubule) allows a large volume of ?uid to be removed from the blood in the glomerulus, the concentrated blood passing on to the uriniferous tubule for removal of parts of its solid contents. Other arteries come straight from the arches and supply the medulla direct; the blood from these passes through another set of capillaries and ?nally into the renal veins. This circulation is con?ned purely to the kidney, although small connections by both arteries and veins exist which pass through the capsule and, joining the lumbar vessels, communicate directly with the aorta.

Function The kidneys work to separate ?uid and certain solids from the blood. The glomeruli ?lter from the blood the non-protein portion of the plasma – around 150–200 litres in 24 hours, 99 per cent of which is reabsorbed on passing through the convoluted tubules.

Three main groups of substances are classi?ed according to their extent of uptake by the tubules:

(1) SUBSTANCES ACTIVELY REABSORBED These include amino acids, glucose, sodium, potassium, calcium, magnesium and chlorine (for more information, see under separate entries).

(2) SUBSTANCES DIFFUSING THROUGH THE TUBULAR EPITHELIUM when their concentration in the ?ltrate exceeds that in the PLASMA, such as UREA, URIC ACID and phosphates.

(3) SUBSTANCES NOT RETURNED TO THE BLOOD from the tubular ?uid, such as CREATINE, accumulate in kidney failure, resulting in general ‘poisoning’ known as URAEMIA.... structure each kidney is about 10 cm long,

(JGA) a microscopic structure within the kidney that is important in regulating blood pressure, body fluid, and electrolytes. It is situated in each nephron, between the afferent arteriole of the glomerulus and the returning distal convoluted tubule of the same nephron. The JGA consists of specialized cells within the distal tubule (the macula densa), which detect the amount of sodium chloride passing through the tubule and can secrete locally acting vasoconstrictor substances that act on the associated afferent arteriole to induce a reduction in filtration pressure (tubuloglomerular feedback). Modified cells within the afferent arterioles secrete *renin in response to a fall in perfusion pressure or feedback from the macula densa and form a central role in the renin-*angiotensin-aldosterone axis. Mesangial cells support and connect the macula densa and the specialized cells in the afferent arteriole and have sympathetic innervation, facilitating the renin response to sympathetic nervous stimulation.... juxtaglomerular apparatus

a common cause of the *nephrotic syndrome in adults. The diagnosis is established by renal biopsy, which shows diffuse global subepithelial deposits within the glomerulus. Most cases of membranous nephropathy are idiopathic, but there are associations with infection (e.g. hepatitis B), malignancy (especially lung cancer), autoimmune disease (e.g. SLE, Hashimoto’s disease), and drugs (e.g. gold and penicillamine). Recent studies suggest that idiopathic membranous nephropathy is an autoimmune disease with antibodies directed against an antigen (PLA2R, a phospholipase A2 receptor) on the *podocyte cell membrane. Without treatment, outcome is very variable: some patients will make a full recovery, while others will progress to end-stage kidney failure. Immunosuppressant treatment is often tried when there is evidence of declining renal function.... membranous nephropathy

the commonest cause of *nephrotic syndrome in children and an important cause of this syndrome in adults. The condition is so named because of the apparent lack of abnormalities seen on light microscopy of biopsy samples. Changes can, however, be seen on electron microscopy, with effacement of the *podocyte foot processes along the glomerular basement membrane. It is postulated that minimal change disease is a T-cell disease and that *cytokine damage to the podocytes leads to loss of the selective filtering characteristics of the glomerulus. The condition usually responds to corticosteroids and has a good prognosis, but there is clinical overlap with primary *focal segmental glomerulosclerosis, which may have similar histological appearances in its early stages, tends not to respond to steroids, and is associated with a poor renal prognosis.... minimal change nephropathy

n. hardening of the arteries and arterioles of the kidneys. Benign nephrosclerosis is associated with essential hypertension. There is preferential involvement of the preglomerular arterial vessels, primarily the afferent arteriole and the interlobular artery. The classic arterial lesion, which is termed arteriolosclerosis, involves replacement of smooth muscle cells in the media of the vessel by connective tissue. There is often evidence of ischaemia in the glomerulus and *tubulointerstitium. Functionally there may be some degree of renal impairment. End-stage renal failure is uncommon, but more likely to occur in Afro-Caribbeans. Malignant nephrosclerosis is the hallmark of *malignant hypertension, with arterioles showing mucoid change, endothelial cell swelling, and fibrinoid necrosis. The lumen of the vessel is reduced and red cells fragmented in their passage through the narrowing. The kidney shows petechial haemorrhage on the subcapsular surface, with mottling and areas of infarction. Malignant nephrosclerosis can lead to a very rapid destruction of renal function and is recognized as a potential cause of acute renal failure.... nephrosclerosis