kidneys

kidneys The kidneys are situated on each side of the vertebral column, at the level of the last (twelfth) rib. Each kidney is about 12 cm long and weighs about 150 g — about the size of a fist. Despite their small size, the two kidneys receive an enormous blood flow — about 1.2 litres/min in an adult — which is a quarter of the total output of the heart (5 litres/min).

One of the main functions of the kidneys is the removal from the body (excretion) of waste products such as urea, uric acid, and creatinine. However, the kidneys' role is not merely excretion. They are also regulatory organs, controlling the volume and the composition of the body fluids and maintaining the correct osmolality, ion concentrations, and acid–base status of the body.

Each kidney is bean-shaped, with a slit opening — termed the hilus — through which pass the renal artery and vein, the renal nerves and lymphatics, and the ureter, which connects the kidney to the bladder (Fig. 1). A tough connective tissue capsule covers the outer layer of the kidney, the cortex. The deeper part of the kidney, the medulla, consists of a number (6–18) of conical pyramids, the tips of which (papillae) project into the funnel-shaped urine collectors — the renal calyxes (calices) — which merge to form the funnel-shaped upper end of the ureter — the renal pelvis. (Renal, pertaining to the kidney, from its Latin name, ren.)

The nephron is the functional unit of the kidney. (Nephros is the Greek for kidney.) Each kidney has about one million nephrons, and the total length of the nephrons in the body is about 100 miles!

The nephron begins as a Bowman's capsule — the blind end of the nephron — invaginated by a knot of capillaries, the glomerulus (glomerular capillaries). A Bowman's capsule and its glomerular capillaries are together termed a renal corpuscle. Sir William Bowman, British surgeon and histologist, described this in 1842.

The rest of the nephron consists of the proximal convoluted tubule, proximal straight tubule, loop of Henle, and distal convoluted tubule. The distal tubules join to form collecting tubules which in turn join to form collecting ducts, which open at the tip of the renal papilla (Fig. 2).

The Bowman's capsules, proximal tubules, and distal tubules are situated in the renal cortex, whereas the loops of Henle and the collecting ducts extend down through the medulla.

The function of the kidneys is to produce urine, a fluid of variable volume and composition (within limits), depending on the need of the body to excrete or conserve water or solutes. The first step in the production of urine is the filtration of plasma passing through the kidney. This filtration (sometimes called ultrafiltration as it occurs at the molecular level rather than gross particle level) occurs from the glomerular capillaries into the Bowman's capsule to form tubular fluid. The glomerular filter prevents plasma proteins from passing into the nephrons, but is permeable to all other plasma constituents (such as ions, glucose, amino acids, urea, etc). Thus filtration in the kidney is essentially non-selective — substances which the body needs to retain are filtered, as well as those substances which need to be excreted.

Filtration is the bulk flow of water through a semipermeable membrane (filter), carrying with it those solutes which can pass through the filter. As mentioned above, the glomerular filter only excludes plasma proteins. Water moves by bulk flow through the filter as a consequence of pressure gradients. Immediately upstream and downstream from the glomerular capillaries, there are blood vessels which have smooth muscle in their walls, so that they can constrict or dilate, and so alter the resistance to the flow of blood. These vessels are, respectively, the afferent and efferent arterioles. They permit precise regulation of the hydrostatic pressure of the blood in the glomerular capillaries, which is maintained at a higher level than in capillaries in other parts of the body. This force drives plasma from the glomerular capillaries into the nephrons. However, two forces work in opposition to this movement. One is the osmotic pressure exerted by the plasma proteins, which increases as filtration proceeds and the proteins, because they are not filtered, get more concentrated. The other force opposing filtration is the hydrostatic pressure within the Bowman's capsule. The resultant is a net filtration pressure which diminishes as blood flows through the glomerlus. The amount of filtration that actually occurs is known as the glomerular filtration rate, or GFR. It is about 120 ml/min (180 l/day). This seems an enormous volume — and it is an enormous volume — but it is important to realize that it is only a small fraction of the total plasma delivered to the kidneys in the blood. In this respect, the kidneys are rather different from our everyday experiences of filters. For example, when we make filter coffee, we pour water over coffee in the filter, and essentially all the water goes through the filter, leaving a ‘sludge’ of coffee grounds in the filter. If all of the plasma delivered to the kidneys passed through the glomerular filters into the nephrons, the filters would be clogged with a ‘sludge’ of red cells, white cells, and plasma proteins. This is prevented because only 20% of the plasma arriving at the filter actually passes through. The remaining 80% continues into the efferent arterioles.

The volume of plasma in the whole of the circulating blood is only about 3 litres, yet we filter 180 litres per day of it. This apparently paradoxical situation is possible because, after filtration, almost all (99%) of the plasma is reabsorbed along the nephron, so can be filtered again and again (60 times a day!). The selectivity of the kidney — how it is able to conserve some substances and excrete others — is due to the transport processes (reabsorption and secretion) which occur along the nephron, modifying the composition of the glomerular filtrate.

In the nephrons, the terms ‘reabsorption’ and ‘secretion’ indicate the direction of movement. Reabsorption is movement of a substance from the tubular fluid, through the tubular cells or between them and thence into the blood. Secretion is movement in the opposite direction.

If a transport process is directly linked to the consumption of metabolic energy, it is termed ‘active’. In the kidney, the quantitatively most important active transport process is the reabsorption of sodium ions (Na⁺). Up to 80% of the kidneys' oxygen consumption drives this process, and because the energy comes from the breakdown of adenosine triphosphate (ATP), Na⁺ active transporters are termed ATPases. There are many other transporter molecules in the nephron cells, many driven by gradients (e.g. for Na⁺) set up by active transport. Such transport is termed ‘secondary active’ for example, glucose reabsorption is via a transporter which also carries Na⁺ into the cell, with the driving force being the Na⁺ concentration gradient set up by the active transport of Na⁺ out of the cell. In addition to ATPases and transporter molecules, nephron cell membranes also contain proteins which constitute ‘channels’ for the passage of ions, neutral molecules or water.

The proximal tubule reabsorbs about 70% of the filtered Na⁺, 70% of the filtered water, and, normally, 100% of the filtered glucose and amino acids. Diabetes mellitus, the condition in which glucose is excreted in the urine, is caused by the failure to maintain the normal plasma level of glucose. In diabetes mellitus the plasma glucose concentration is increased, so the filtered load of glucose is increased; if the increase is big enough the nephrons are unable to reabsorb it all, and some appears in the urine.

The sodium which is reabsorbed in the ascending loop of Henle is not accompanied by water, since this part of the nephron is impermeable to water. Consequently, Na⁺ transport at this site lowers the solute concentration of the tubular fluid, and raises that of the fluid in the interstitial space of the medulla, which surrounds the tubules. This high medullary concentration is the osmotic driving force for water reabsorption in the collecting tubules under the influence of ADH (see below).

Just how efficient the kidneys are at controlling our body fluid volume is demonstrated by the constancy of the body weight from day to day. Even if you spend the evening in the pub and drink a couple of kilograms of beer, your body weight will be back to normal the next day!

The volume of urine excreted by the kidneys can vary between 400 ml/day, and about 25 L/day. The main determinants of urine volume are the osmotic concentration of the body fluids, and the effective circulating volume (the volume of blood circulating around the body in the vascular system). These regulate the urine volume primarily by affecting the release or production of hormones which control renal function.

If our fluid intake is less than the fluid loss, the body fluid osmotic concentration (osmolality) increases — the solutes of the body are in a smaller volume than normal, so their concentration is higher. This increased osmotic concentration is detected by ‘osmoreceptors’ in the brain, and these lead to the release, from the posterior pituitary gland, of the peptide antidiuretic hormone (ADH), also called vasopressin. This hormone circulates in the blood and binds to ‘V2’ receptors on the cells of the kidneys' collecting tubules. It causes them in effect to become more permeable to water, by incorporating water channels in their cell membranes. Because there is always an osmotic gradient tending to move water out of these tubules into the fluid around them and thence into the blood, more water is reabsorbed, the volume of urine is decreased and it becomes more concentrated. The raised osmolality of the body fluids is thus corrected. Because of this continual homeostatic mechanism, the urine volume, which can range from 400 ml/day to 25 litres/day is primarily determined by the level of circulating ADH. A typical volume is 1.5 litres/day.

Decreases in the effective circulating volume also increase ADH release, but in addition such decreases increase the release of renin from the juxtaglomerular apparatus of the kidney (a region of each nephron where the afferent arteriole and distal tubule are in contact). Renin is an enzyme, which acts on a plasma protein (a₂ globulin) to release a 10-amino acid peptide, angiotensin I. This in turn is converted, by an enzyme present in blood vessel walls, (ACE — angiotensin converting enzyme), to an 8 amino acid peptide, angiotensin II.

Angiotensin II increases nephron Na⁺ reabsorption. Since water follows Na⁺, water reabsorption also increases, and urine volume falls. Angiotensin II acts directly on the nephrons, and also causes ADH release and the release of another Na⁺-retaining hormone, aldosterone.

Another important regulatory function of the kidney is the control of acid–base homeostasis. In general, the metabolism of the body produces excess H⁺, and this is secreted into the urine by the nephron cells. The pH of the blood and extracellular fluid is kept constant at 7.4, but to achieve this, the kidneys can vary the urine pH from 4.5–8.0.

Kidney function may become impaired, leading to renal failure. There are many potential causes of renal failure, including reduction of the renal blood supply (e.g. as a result of major haemorrhage), toxins and disease organisms, and blockages of the urinary tract. If the kidneys fail, one of the first signs is the accumulation of urea and other nitrogenous waste in the blood —uraemia. This may require treatment by dialysis or by organ transplantation. However, other problems associated with failing kidneys relate to the fact that the kidneys are themselves important endocrine glands. They produce the hormone erythropoietin, which stimulates bone marrow to produce red blood cells, and also convert the precursor form of vitamin D to the active form. Both of these functions can be disrupted in renal failure, leading to anaemia and to disturbance of calcium supply to the bones.

If just one kidney fails, or is surgically removed, then changes take place in the remaining one to enable it to maintain homeostasis. Although the number of nephrons in the surviving kidney does not increase, the glomerular filtration rate of each individual nephron increases, so that the overall glomerular filtration rate increases to approach that which was previously achieved with two kidneys.

Chris Lote

Bibliography

Lote, C. J. (2000). Principles of renal physiology, (4th edn). Kluwer, Amsterdam.

See also acid–base homeostasis; dialysis; urine; water balance.See urogenital system.