Renal physiology
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Renal physiology is the study of the physiology of the kidneys.
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Functions of the kidney
Filtration of wastes
The kidney removes from the blood many organic wastes, ammonia, urea, and other metabolic byproducts that may otherwise be harmful to the body.
Secretion of hormones
- Secretion of erythropoietin, which regulates red blood cell production in the bone marrow.
- Secretion of renin, which is a key part of the renin-angiotensin-aldosterone system.
- Secretion of the active form of vitamin D, calcitriol, and prostaglandins.
Sodium and water homeostasis
There is a stable balance of sodium and water in the body. The major homeostatic control point for maintaining this stable balance is renal excretion.
The kidney is directed to excrete or retain sodium via the action of aldosterone, antidiuretic hormone (ADH, or vasopressin), atrial natriuretic peptide (ANP), and other hormones.
Acid-base homeostasis
The body is very sensitive to its pH level. Outside the range of pH that is compatible with life, proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself.
The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced.
Sources of acid gain:
- Carbon dioxide (since CO2 and H2O form H2CO3, carbonic acid, in the presence of carbonic anhydrase)
- Production of nonvolatile acids from the metabolism of proteins and other organic molecules
- Loss of bicarbonate in diarrhea or urine
Sources of acid loss:
- Use of hydrogen ions in the metabolism of various organic anions
- Loss of acid in the vomitus or urine
When acid loss exceeds acid gain, alkalosis occurs. When gain exceeds loss acidosis occurs. There are various renal responses to acidosis and alkalosis.
Responses to acidosis:
- Bicarbonate is added to the blood plasma by tubular cells.
- Tubular cells reabsorb more bicarbonate from the tubular fluid.
- Collecting duct cells secrete more hydrogen and generate more bicarbonate.
- Ammoniagenesis leads to increased buffer formation (in the form of NH3)
Responses to alkalosis:
- Excretion of bicarbonate in urine.
- This is caused by lowered rate of hydrogen ion secretion from the tubular epithelial cells.
- This is also caused by lowered rates of glutamine metabolism and ammonia excretion.
Buffering of hydrogen ions
Any substance that can reversibly bind hydrogen ions is called a buffer. Hydrogen ions are buffered by extracellular (e.g., bicarbonate) and intracellular buffers (including proteins and phosphate).
Mechanisms
The kidney's ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion.
Filtration
The blood is filtered by nephrons, the functional units of the kidney. Each nephron begins in a renal corpuscle, which is composed of a glomerulus enclosed in a Bowman's capsule. Cells, proteins, and other large molecules are filtered out of the glomerulus by a process of ultrafiltration, leaving an ultrafiltrate that resembles plasma (except that the ultrafiltrate has negligible plasma proteins) to enter Bowman's space. Filtration is driven by Starling forces.
The ultrafiltrate is passed through, in turn, the proximal tubule, the loop of Henle, the distal convoluted tubule, and a series of collecting ducts to form urine.
Reabsorption
Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. It is called reabsorption (and not absorption) because these substances have already been absorbed once (particularly in the intestines). Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), and then the transport of these substances from the interstitium into the bloodstream. These transport processes are driven by Starling forces, diffusion, and active transport.
In some cases, reabsorption is indirect. For example, bicarbonate (HCO3-) does not have a transporter, so its reabsorption involves a series of reactions in the tubule lumen and tubular epithelium. It begins with the active secretion of a hydrogen ion (H+) into the tubule fluid via a Na/H exchanger:
- In the lumen
- The H+ combines with HCO3- to form carbonic acid (H2CO3)
- Luminal carbonic anhydrase enzymatically converts H2CO3 into H2O and CO2
- CO2 freely diffuses into the cell
- In the epithelial cell
- Cytoplasmic carbonic anhydrase converts the CO2 and H2O (which is abundant in the cell) into H2CO3
- H2CO3 readily dissociates into H+ and HCO3-
- HCO3- is facilitated out of the cell's basolateral membrane
Some key regulatory hormones for reabsorption include aldosterone, which stimulates active sodium reabsorption, and antidiuretic hormone, which stimulates passive water reabsorption. Both hormones exert their effects principally on the collecting ducts.
Secretion
Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport.
Usually only a few substances are secreted. These substances are present in great excess, or are natural poisons.
Measurement of renal function
A simple means of estimating renal function is to measure pH, blood urea nitrogen, creatinine, and basic electrolytes (including sodium, potassium, chloride, and bicarbonate). As the kidney is the most important organ in controlling these values, any derangement in these values would suggest renal impairment.
A more formal test of renal function would be to measure the glomerular filtration rate; usually a creatinine clearance test is performed but other markers, such as the plant polysaccharide inulin, may be used as well.
Para-aminohippuric acid (PAH) is a renal analysis tool which estimates the total renal blood flow.