, shown here, is the functional unit of the kidneys. Its parts are labelled except the (gray)
connecting tubule located after the (dark red) distal convoluted tubule and before the large (gray) collecting duct (mislabeled
collection duct). The kidneys excrete a variety of waste products produced by
metabolism into the urine. The microscopic structural and functional unit of the kidney is the
nephron. It processes the blood supplied to it via filtration, reabsorption, secretion and excretion; the consequence of those processes is the production of
urine. These include the nitrogenous wastes
urea, from protein
catabolism, and
uric acid, from
nucleic acid metabolism. The ability of mammals and some birds to concentrate wastes into a volume of urine much smaller than the volume of blood from which the wastes were extracted is dependent on an elaborate
countercurrent multiplication mechanism. This requires several independent nephron characteristics to operate: a tight hairpin configuration of the tubules, water and ion permeability in the descending limb of the loop, water impermeability in the ascending loop, and active ion transport out of most of the ascending limb. In addition, passive
countercurrent exchange by the vessels carrying the blood supply to the nephron is essential for enabling this function. The kidney participates in whole-body
homeostasis, regulating
acid–base balance,
electrolyte concentrations,
extracellular fluid volume, and
blood pressure. The kidney accomplishes these homeostatic functions both independently and in concert with other organs, particularly those of the
endocrine system. Various endocrine hormones coordinate these endocrine functions; these include
renin,
angiotensin II,
aldosterone,
antidiuretic hormone, and
atrial natriuretic peptide, among others.
Formation of urine .
Filtration Filtration, which takes place at the
renal corpuscle, is the process by which cells and large proteins are retained while materials of smaller molecular weights are filtered from the blood to make an
ultrafiltrate that eventually becomes urine. The adult human kidney generates approximately 180 liters of filtrate a day, most of which is reabsorbed. The normal range for a twenty four hour urine volume collection is 800 to 2,000 milliliters per day. The process is also known as hydrostatic filtration due to the hydrostatic pressure exerted on the capillary walls.
Reabsorption Reabsorption is the transport of molecules from this ultrafiltrate and into the peritubular capillary network that surrounds the nephron tubules. It is accomplished via selective
receptors on the luminal cell membrane. Water is 55% reabsorbed in the proximal tubule. Glucose at normal plasma levels is completely reabsorbed in the proximal tubule. The mechanism for this is the Na+/glucose cotransporter. A plasma level of 350 mg/dL will fully saturate the transporters and glucose will be lost in the urine. A plasma glucose level of approximately 160 is sufficient to allow glucosuria, which is an important clinical clue to diabetes mellitus. Amino acids are reabsorbed by sodium dependent transporters in the proximal tubule.
Hartnup disease is a deficiency of the tryptophan amino acid transporter, which results in
pellagra.
Secretion Secretion is the reverse of reabsorption: molecules are transported from the peritubular capillary through the interstitial fluid, then through the renal tubular cell and into the ultrafiltrate.
Excretion The last step in the processing of the ultrafiltrate is
excretion: the ultrafiltrate passes out of the nephron and travels through a tube called the
collecting duct, which is part of the
collecting duct system, and then to the ureters where it is renamed
urine. In addition to transporting the ultrafiltrate, the collecting duct also takes part in reabsorption.
Hormone secretion The kidneys secrete a variety of
hormones, including
erythropoietin,
calcitriol, and
renin.
Erythropoietin (EPO) is released in response to
hypoxia (low levels of oxygen at tissue level) in the renal circulation. It stimulates
erythropoiesis (production of red blood cells) in the
bone marrow.
Calcitriol, the activated form of
vitamin D, promotes intestinal absorption of
calcium and the renal
reabsorption of
phosphate. Renin is an
enzyme which regulates
angiotensin and
aldosterone levels.
Blood pressure regulation Although the kidney cannot directly sense blood, long-term regulation of
blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the
extracellular fluid compartment, the size of which depends on the plasma
sodium concentration. Renin is the first in a series of important chemical messengers that make up the
renin–angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones
angiotensin II and
aldosterone. Each hormone acts via multiple mechanisms, but both increase the kidney's absorption of
sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure. Conversely, when renin levels are low, angiotensin II and aldosterone levels decrease, contracting the extracellular fluid compartment, and decreasing blood pressure.
Acid–base balance The two organ systems that help regulate the body's acid–base balance are the kidneys and lungs.
Acid–base homeostasis is the maintenance of
pH around a value of 7.4. The lungs are the part of respiratory system which helps to maintain acid–base homeostasis by regulating
carbon dioxide (CO2) concentration in the blood. The respiratory system is the first line of defense when the body experiences and acid–base problem. It attempts to return the body pH to a value of 7.4 by controlling the respiratory rate. When the body is experiencing acidic conditions, it will increase the respiratory rate which in turn drives off CO2 and decreases the H+ concentration, therefore increasing the pH. In basic conditions, the respiratory rate will slow down so that the body holds onto more CO2 and increases the H+ concentration and decreases the pH. The kidneys have two cells that help to maintain acid-base homeostasis: intercalated A and B cells. The intercalated A cells are stimulated when the body is experiencing acidic conditions. Under acidic conditions, the high concentration of CO2 in the blood creates a gradient for CO2 to move into the cell and push the reaction HCO3 + H ↔ H2CO3 ↔ CO2 + H2O to the left. On the luminal side of the cell there is a H+ pump and a H/K exchanger. These pumps move H+ against their gradient and therefore require ATP. These cells will remove H+ from the blood and move it to the filtrate which helps to increase the pH of the blood. On the basal side of the cell there is a HCO3/Cl exchanger and a Cl/K co-transporter (facilitated diffusion). When the reaction is pushed to the left it also increases the HCO3 concentration in the cell and HCO3 is then able to move out into the blood which additionally raises the pH. The intercalated B cell responds very similarly, however, the membrane proteins are flipped from the intercalated A cells: the proton pumps are on the basal side and the HCO3/Cl exchanger and K/Cl co-transporter are on the luminal side. They function the same, but now release protons into the blood to decrease the pH.
Regulation of osmolality The kidneys help maintain the water and salt level of the body. Any significant rise in
plasma osmolality is detected by the
hypothalamus, which communicates directly with the
posterior pituitary gland. An increase in osmolality causes the gland to secrete
antidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels.
Measuring function Various calculations and methods are used to try to measure kidney function.
Renal clearance is the volume of plasma from which the substance is completely cleared from the blood per unit time. The
filtration fraction is the amount of plasma that is actually filtered through the kidney. This can be defined using the equation. The kidney is a very complex organ and
mathematical modelling has been used to better understand kidney function at several scales, including fluid uptake and secretion. ==Clinical significance==