Kidneys reabsorption

Vitamin D is a family of closely related molecules that prevent rickets, a childhood disease characterized by inadequate intestinal absorption and kidney reabsorption of calcium and phosphate. These inadequacies eventually lead to the demineralization of bones. The symptoms of rickets include bowlegs,... 

FUNCTION Stimulates kidney reabsorption of sodium back into the circulation, with loss of potassium. 

Parathyroid hormone (PTH) Primary hyperparathyroidism causes hypercalcemia, hypophosphatemia, and increased urinary cAMP hypoparathyroidism causes hypocalcemia and hyperphosphatemia, often with soft-tissue calcification and tetany and convulsions. Binds to cell-surface receptors and activates adenylate cyclase increases bone mineralization and activity of renal lot-hydroxylase in kidney, reabsorption of Ca " " increases and reabsorption of phosphate decreases. 

Uricosuric agents increase the rate of excretion of uric acid. In humans, urate is filtered, secreted, and reabsorbed by the kidneys. Reabsorption predominates, and the amount excreted usually is 10% of that filtered. This process is mediated by a specific transporter, which can be inhibited see Chapter 2). 

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

In subsequent studies attempting to find a correlation of physicochemical properties and antimicrobial activity, other parameters have been employed, such as Hammett O values, electronic distribution calculated by molecular orbital methods, spectral characteristics, and hydrophobicity constants. No new insight on the role of physiochemical properties of the sulfonamides has resulted. Acid dissociation appears to play a predominant role, since it affects aqueous solubiUty, partition coefficient and transport across membranes, protein binding, tubular secretion, and reabsorption in the kidneys. An exhaustive discussion of these studies has been provided (10). 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

In the kidney, ANG II reduces renal blood flow and constricts preferentially the efferent arteriole of the glomerulus with the result of increased glomerular filtration pressure. ANG II further enhances renal sodium and water reabsorption at the proximal tubulus. ACE inhibitors thus increase renal blood flow and decrease sodium and water retention. Furthermore, ACE inhibitors are nephroprotective, delaying the progression of glomerulosclerosis. This also appears to be a result of reduced ANG II levels and is at least partially independent from pressure reduction. On the other hand, ACE inhibitors decrease glomerular filtration pressure due to the lack of ANG II-mediated constriction of the efferent arterioles. Thus, one important undesired effect of ACE inhibitors is impaired glomerular filtration rate and impaired kidney function. 

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

Oedema refers to an accumulation of interstitial fluid to a point where it is palpable or visible. In general this point is reached with a fluid volume of 2-3 liters. Oedema formation is the result of a shift of fluid into the interstitial space due to primary disturbances in the hydraulic forces governing transcapillary fluid transport and of subsequent excessive fluid reabsorption by the kidneys. Deranged capillary hydraulic pressures initiate oedema formation in congestive heart failure, and liver cirrhosis whereas a deranged plasma oncotic pressure... 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Vasopressin (Rtressin Synthetic) and its derivatives, namely lypressin (Diapid) and desmopressin (DDAVP), regulate the reabsorption of water by the kidneys. Vasopressin is secreted by the pituitary when body fluids must be conserved. An example of this mechanism may be seen when an individual has severe vomiting and diarrhea with little or no fluid intake. When this and similar conditions are present, die posterior pituitary releases the hormone vasopressin, water in die kidneys is reabsorbed into die blood (ie, conserved), and die urine becomes concentrated. Vasopressin exhibits its greatest activity on die renal tubular epithelium, where it promotes water resoqition and smooth muscle contraction throughout die vascular bed. Vasopressin has some vasopressor activity. 

Excretion via the kidney can be a straightforward question of glomerular filtration, followed by passage down the kidney tubules into the bladder. However, there can also be excretion and reabsorption across the tubular wall. This may happen if an ionized form within the tubule is converted into its nonpolar nonionized form because of a change in pH. The nonionized form can then diffuse across the tubular wall into plasma. Additionally, there are active transport systems for the excretion of lipophilic acids and bases across the wall of the proximal tubule. The antibiotic penicillin can be excreted in this way. 

Sodium SGLTl -dependent unidirectionai transporter Small intestine and kidney Active uptake of glucose from lumen of intestine and reabsorption of glucose in proximal tubule of kidney against a concentration gradient... 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

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