Filtration glomerular

The first step in the formation of urine is glomerular filtration. The barrier to filtration is designed to facilitate the movement of fluid from the glomerular capillaries into Bowman s capsule without any loss of cellular elements or plasma proteins. Maximizing GFR has two advantages  

Filtration barrier. The filtration barrier is composed of three structures  

Like the walls of other capillaries, the glomerular capillary wall consists of a single layer of endothelial cells. However, these cells are specialized in that they are fenestrated. The presence of large pores in these capillaries makes them 100 times more permeable than the typical capillary. These pores are too small, however, to permit the passage of blood cells through them. 

The basement membrane is an acellular meshwork consisting of collagen and glycoproteins. The collagen provides structural support and the negatively charged glycoproteins prevent the filtration of plasma proteins into Bowman s capsule. 

The inner wall of Bowman s capsule consists of specialized epithelial cells referred to as podocytes. This layer of epithelial cells is not continuous instead, the podocytes have foot-like processes that project outward. The processes of one podocyte interdigitate with the processes of an adjacent podocyte, forming narrow filtration slits. These slits provide an ample route for the filtration of fluid. 

During the normal operation of mammalian kidneys, a large amount of fluid (about one fifth to one third of the plasma voliune) passes through the endothelium of the glomerular capillaries. This process may be regarded as ultrafiltration, resulting from an imbalance in transcapillary hydraulic (AP) and osmotic pressures (An). The flow rate J can be written as 

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The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

Technetium-99m mertiatide (A/-[Ai-[A/-[(benzoylthio)acetyl]glycyl]glycine) is a renal imaging agent. It is excreted by the kidneys via active tubular secretion and glomerular filtration. The kit vial is reconstituted by using 740—3700 MBq (20—100 mCi) of Tc pertechnetate and boiling for 10 minutes. 

The overall effect in most animals is to stimulate intestinal absorption of calcium with a concomitant increase in semm calcium and a reduction in parathyroid hormone (PTH). Modest hypercalcemia allows the glomerular filtration rate to remain stable and hypercalciuria to occur because of increased filtered load of calcium and reduction of tubular resorption of calcium with reduced PTH. However, with further increases in semm calcium, the glomerular filtration rate decreases, resulting in an even more rapid increase in semm calcium and the subsequent fall in urinary calcium. 

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. 

Aldosterone, the most potent of the mineralocorticoids (Figure 25.43), is involved in the regulation of sodium and potassium balances in tissues. Aldosterone increases the kidney s capacity to absorb Na, Cl, and HgO from the glomerular filtrate in the kidney tubules. 

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. 

In the kidney, bradykinin increases renal blood flow, whereas glomerular filtration rate remains unaffected. 

As a general rule, increases of renal blood flow and/ or glomerular filtration rate (GFR) correlate rather well with increased urinary excretion of solutes and water. The underlying causes for this correlation are not fully understood, but they reflect incomplete adjustments of tubular reabsorption to an increase of tubular electrolyte load. 

Glomerular filtration rate (GFR) is the volume of plasma-like fluid that is filtered per unit time across the glomerular capillary membranes to enter the tubular space. Filtrate formation is driven by the net filtration pressure that is equal to the capillary hydrostatic pressure diminished by the sum of capillary oncotic... 

Luzius Dettli was not only the first who described the linear function for the dependence of diug elimination on glomerular filtration rate. He was also the first who proposed the fundamental dose adjustment recommendation, the proportional dose reduction rule. Two alternatives are given to either reduce the single dose (D) or extend the interval (Tau). 

Urographic contrast agents are contrast agents which possess the characteristics of very little enteral absotp-tion, almost no protein binding or uptake into cells, an extracellular (interstitial) distribution and glomerular filtration. These pharmacokinetics are due to very little interaction with the organism, resulting in very low toxicity, preferably nonionic (neutral) molecules. 

Decreased serum proteins Decreased renal mass, blood flow, and glomerular filtration rate... 

West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J Pediatr 32a 10-18. 

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. 

G-CSF Granulocyte colony-stimulating factor GDP Guanosine 5 -diphosphate GEC Glomerular epithelial cell GF-1 An insulin-like growth factor GFR Glomerular filtration rate... 

Small studies have shown improvement in glomerular filtration rate and gastrointestinal mucosal perfusion when norepinephrine is utilized in resuscitated septic shock... 

Another key feature of the thiazide-type diuretics is their limited efficacy in patients whose estimated renal function is reduced, such as the elderly. For example, patients with estimates of reduced renal function, such as those with a glomerular filtration rate (GFR) below 30 mL/minute, should be considered for more potent loop type diuretics such as furosemide. Clinicians often fail to either reconsider the role of thiazide diuretics prescribed to individuals whose renal function has been declining or fail to recognize the likely prevalence of renal compromise in the elderly to begin with. 

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