Filtration and reabsorption

A reasonable assumption is that the active secretion mechanism in the kidney can also be described by the well-stirred model. However, the kidneys have several mechanisms that may determine renal clearance of a drug, including passive filtration and reabsorption. 

The amount of calcium excreted into the urine reflects intestinal absorption, skeletal resorption, and renal tubular filtration and reabsorption. Under fasting conditions, the intestinal and renal components are relatively fixed, and calcium excretion (miUigrams per 100 mL of GF) in the fasting state is used to assess the skeletal component. A value exceeding 0.16 mg/lOO mL (>0.04 mmol/L) of GF usually implies an increase in osteoclastic bone resorption. This test is useftil in assessing renal stone disease and high-turnover osteoporosis. 

The autoregulation response should ultimately arise from the action of multiple precapfllary sphincters and resistance arterioles in the microcirculation. The control of flow in a microvascular model was analyzed by Mayrovitz et al. [1978]. This model included muscular arterial and venous vasomotion, capillary filtration and reabsorption, and lymph flow. Tissue pressure was assumed to be regulated and was used to provide the control pathway for the activation of the precapiUary sphincter. Local flow was found to vary considerably with periodic sphincter activity. This model demonstrated that autoregulation of flow is likely to find its genesis at the microcirculatory level. 

Several intrarenal factors are involved in the production of concentrated urine, including especially the attaiiunent and maintenance of high interstitial osmolality in the medulla as a result of solute filtration and reabsorption, and of the countercurrent concentrating mechanism, which depends in turn on normal medullary blood flow. Urinary concentrating ability can therefore not be associated with a specific aspect of renal function but serves rather as reflection of its general integrity, and can thus prove useful for screening purposes. 

Convection is a process by which a substance is dragged along by the flow of fluid hence the term solvent drag is used to describe this type of transport. The flow is powered by osmotic or hydrostatic pressure gradients which exist across tissue boundaries. The kidney is an example of an organ which depends on hydrostatic pressure-driven convection for filtration of substances by the glomerulus and osmotic-pressure driven convection for solute reabsorption in the proximal tubule. Filtration and reabsorption by blood capillaries depends on Starling s relationship ... 

Interfere wrth action of sulfhydryt enzymes in energy metabolism, causing necrosis in eneigy-dependent proximal tubules most metals are corKentrated in tubule cells during renal filtration and reabsorption... 

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. 

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 and water balance are primarily regulated by the kidney Reductions in nephron mass decrease glomerular filtration and subsequent reabsorption of sodium and water, leading to edema. 

The kidneys are located on the posterior part of the abdomen on either side of the spine, below the diaphragm, and behind the liver and stomach. They are bean-shaped and weigh approximately 150 grams (0.33 lb) each. The primary function of the kidneys is excretion. They work to excrete waste products through a series of steps involving glomerular filtration, secretion, and reabsorption. The kidneys also have several endocrine (e.g., production of erythropoietin and renin) and metabolic (e.g., vitamin D activation and drug metabolism) functions. 

Note that, except for capillary hydrostatic pressure, the magnitude of these forces remains constant throughout the length of the capillary. The capillary hydrostatic pressure decreases steadily as blood flows from the arteriolar end to the venular end of the capillary. The steady decline in this pressure results in filtration of fluid at one end and reabsorption of fluid at the other end of the capillary. 

Increased capillary hydrostatic pressure promotes filtration and inhibits reabsorption. As a result, excess fluid is forced out of the capillary into the interstitial space. An increase in capillary pressure is generally caused by an... 

Sodium reabsorption. Sodium is reabsorbed by different mechanisms as the filtrate progresses through the tubule. Sodium ions leave the filtrate and enter the tubular epithelial cell by way of the following processes (see Figure 19.4) ... 

Sodium is freely filtered at the glomerulus. Therefore, any factor that affects GFR will also affect sodium filtration. As discussed previously, GFR is directly related to RBF. In turn, RBF is determined by blood pressure and the resistance of the afferent arteriole (RBF = AP/R). For example, an increase in blood pressure or a decrease in resistance of the afferent arteriole will increase RBF, GFR, and, consequently, filtration of sodium. The amount of sodium reabsorbed from the tubules is physiologically regulated, primarily by aldosterone and, to a lesser extent, by ANP. Aldosterone promotes reabsorption and ANP inhibits it. The alterations in sodium filtration and sodium reabsorption in response to decreased plasma volume are illustrated in Figure 19.6. 

The rate of total body clearance accounted for by the kidney. Its magnitude is determined by the net effects of glomerular filtration, tubular secretion and reabsorption, renal blood flow, and protein binding. 

The balance of filtration at the glomerulus and reabsorption and secretion in the tubules allows the kidneys to maintain homeostasis of extracellular fluid, nutrients and acid-base balance and to excrete drugs and metabolic waste products. 

Oligonucleotide targeting to the kidney is more feasible than to many other tissues as a result of the glomerular filtration and tubular reabsorption of these poly-anionic agents. The effect is temporary allowing the therapy to be terminated when desired. Up until now, data has only been available on the kinetics and some renal and extra-renal effects of oligonucleotides in healthy animals. 

In calves and cows, SDM was excreted by glomerular filtration minus tubular reabsorption its renal clearance was urine flow correlated, and amounts to half of the creatinine clearance. The SCH2OH hydroxy metabolite was excreted by glomerular filtration and partly by tubular secretion, whereas both Na-SDM and SOH were excreted predominantly by tubular secretion (15 . The main metabolite in urine SCH2OH was 23 to 55 % of the administered dose (Table III). The urine concentration—time curves for SDM and its metabolites are illustrated in Figure 7 for a high SDM dosage. 

In congestive heart failure the drug elimination is retarded due to decreased perfusion and congestion of liver, also reduced glomerular filtration and increased tubular reabsorption. 

The main action of thiazides is exerted on the early segment of distal tubule or cortical diluting segment. They inhibit reabsorption of sodium and chloride. The thiazides enter the tubule partly by glomerular filtration and partly by active secretion into the proximal tubule. At usual therapeutic doses, the major portion of the diuresis is due to an inhibition of reabsorption in the more distal parts of the nephron. 

The methylxanthines—especially theophylline—are weak diuretics. This effect may involve both increased glomerular filtration and reduced tubular sodium reabsorption. The diuresis is not of sufficient magnitude to be therapeutically useful. 

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