Renal tubules function

The proteinuria and aminoaciduria, and acidosis and glucosuria where they occur, are probably caused by reversible inhibition of some functions of the renal tubule. There would appear to be no structural damage to the kidney. However, 2 children developed nephrolithiasis while being treated with a low-lactose diet (B7, C5), The time course of events, when galactose is withdrawn from and returned to the diet, suggests that some metabolite of galactose accumulates in the cells of the renal tubules and has an inhibitory effect on the reabsorption of a number of substances. 

A plethora of methods has been developed to evaluate renal function by dynamic renography and remote analysis of the excretion of renal function markers. The underlying principle is that the kidneys excrete a majority of small hydrophilic molecules and their clearance, secretion, or fixation in the kidney is quantifiable. When a renal marker in plasma is filtered through the glomeruli, the accumulation of the filtrate in the Bowman s capsule. One or more of the following events may occur in the renal tubule once a marker is filtered or is in plasma [171] ... 

The filtered and secreted marker may irreversibly bind to renal tubule, making their quantification in urine of little value. They are primarily used for static imaging of the kidneys and to obtain information about the functional renal mass. Tc-dimercaptosuccinic acid and Tc-glucoheptonate are good examples of such markers [172 -175]. 

Stability The marker for GFR measurement should be biologically inert, which implies the absence of binding to plasma proteins, reabsorption in the renal tubule, deleterious effect on renal function, and intact excretion of the filtrate in the urine without degradation. This biological inert criterion, albeit difficult to achieve synthetically, confers an enormous advantage for speedy regulatory approval, especially if small doses are used. 

Animal studies indicate that the primary toxic effect of uranium exposure is on the kidney, with particular damage to the proximal tubules. Functionally, this may result in increased excretion of glucose and amino acids. Structurally the necrosis of tubular epithelium leads to formation of cellular casts in the urine. If exposure is insufficient to cause death from renal failure, the mbular lesion is reversible with epithelial regeneration. Although bone is the other major site of deposition, there is no evidence of toxic or radiocarcinogenic effects to bone or bone marrow from experimental studies. ... 

Desoxycorticosterone causes an increase in reabsorption of sodium ions and excretion of potassium ions from the renal tubules, which leads to increased tissue hydrophilicity. This facilitates an elevated volume of plasma and increased arterial pressure. Muscle tonicity and work capability are increased. It is used for an insufficiency of function of the adrenal cortex, myasthenia, asthenia, adynamia, and overall muscle weakness. Synonyms of this drug are percorten, docabolin, cortitron, and others. 

Hartnup disorder Is a rare condition caused by impaired resorption of neutral amino acids (especially tryptophan, alanine, threonine, glutamine, and histidine) In the renal tubules and malabsorption In the Intestine, resulting from mutations that lead to defective function of a neutral amino acid transporter. 

Lithium is completely absorbed after oral administration reaching peak concentrations after 1-3 hours. Lithium is not metabolized and almost completely excreted unchanged in the urine with a half-life of on average 24 hours, but increasing to 40 hours or longer in the elderly and in patients with compromised renal function. After excretion 70-80% is reabsorbed by proximal renal tubule where it competes with sodium for reabsorption. Therefore low sodium levels decrease lithium excretion with consequent risks for lithium toxicity. 

Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1957 that a practical and powerful diuretic agent (chlorothiazide) became available for widespread use. 

This chapter is divided into three sections. The first section covers renal tubule transport mechanisms. The nephron is divided structurally and functionally into several segments (Figure 15-1, Table 15-1). Many diuretics exert their effects on specific membrane transport proteins in renal tubular epithelial cells. Other diuretics exert osmotic effects that prevent water reabsorption (mannitol), inhibit enzymes (acetazolamide), or interfere with hormone receptors in renal epithelial cells (aldosterone receptor blockers). The physiology of each segment is closely linked to the basic pharmacology of the drugs acting there, which is discussed in the second section. Finally, the clinical applications of diuretics are discussed in the third section. 

A form of salt loss in infancy was long considered to be due to renal tubules that were refractory to aldosterone. Recent studies have described variant roots of the condition, either mutations in the mineralocorticoid receptor, the genes coding the epithelial sodium channel (ENaC), or other causes [6]. Many infant patients recover spontaneously, probably due to maturation of proximal tubular function. 

A family of integral proteins discovered by Peter Agre, the aquaporins (AQPs), provide channels for rapid movement of water molecules across all plasma membranes (Table 11-6 lists a few examples). Ten aquaporins are known in humans, each with its specialized role. Erythrocytes, which swell or shrink rapidly in response to abrupt changes in extracellular os-molarity as blood travels through the renal medulla, have a high density of aqua-porin in their plasma membranes (2 X 105 copies of AQP-1 per cell). In the nephron (the functional unit of the kidney), the plasma membranes of proximal renal tubule cells have five different aquaporin types. 

Most diuretics act upon a single anatomic segment of the nephron (Figure 15-1). Because these segments have distinctive transport functions, the first section of this chapter is devoted to a review of those features of renal tubule physiology that are relevant to diuretic action. The second section is devoted to the basic pharmacology of diuretics, and the third section discusses the clinical applications of these drugs. 

Chloramphenicol may be administered either intravenously or orally. It is completely absorbed via the oral route because of its lipophilic nature and is widely distributed throughout the body. It readily enters the normal CSF. The drug inhibits the hepatic mixed function oxidases. Excretion of the drug depends on its conversion in the liver to a glucuronide that is then secreted by the renal tubule. Only about 10% of the parent compound is excreted by glomerular filtration. 

Carnitine is present in biological systems as both carnitine and acylcarnitines generated in tissues (see next section). Carnitine deficiency may be a primary defect due to a genetic defect in carnitine transport systems or may be secondary to other metabolic derangements. Normal carnitine homeostasis requires reabsorption of carnitine in the renal tubule via a specific transport protein. This same transport protein is responsible for the accumulation of carnitine in heart and skeletal muscle. If this transport system is not functional, then carnitine cannot reach tissues, and primary carnitine... 

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