Renal compensatory mechanisms

In addition to excess sodium intake, abnormal renal sodium retention may be the primary event in the development of hypertension, and it includes abnormalities in the pressure-natriuresis mechanism. In hypertensive individuals, this theory proposes a shift in the control mechanism preventing the normalization of blood pressure. The mechanisms behind the resetting of the pressure-natriuresis curve may include afferent arteriolar vasoconstriction, decreased glomerular ultrafiltration, or an increase in tubular sodium reabsorption.4 Other theories supporting abnormal renal sodium retention suggest a congenital reduction in the number of nephrons, enhanced renin secretion from nephrons that are ischemic, or an acquired compensatory mechanism for renal sodium retention.9... 

Cardiac glycosides bring about diuresis by increasing both cardiac output and renal blood flow the latter in turn reverses the renal compensatory mechanism activated in congestive heart failure. Consequently, the production of aldosterone is reduced, sodium retention is reversed, and the excretion of edematous fluid is enhanced (Figure 35.5). 

Chronic renal failure is associated with long-term exposure to toxins and is mostly related to the secondary pathological changes triggered by the initial injury. These secondary changes are compensatory mechanisms to maintain the function of the whole kidney, but they eventually result in... 

In each form of cholestasis, atypical bile adds, such as monohydroxy bile acids, aUo-bile adds, 1- or 6-hydroxylated bile acids and their sulphated or glucuronidated derivatives, are found in the sermn and/or urine. In cholestasis, the increase in the neosynthesis of atypical bile adds that pass into the kidney can be seen as a compensatory mechanism which eliminates potentially hepatotoxic bile acids by renal clearance. The highest renal excretion quota is demonstrated by tetrahydroxy bile acids. 

Furosemide is a widely used loop diuretic indicated for the treatment of different pathological conditions such as congestive heart failure, hepatic cirrhosis, and chronic renal failure. It has a narrow absorption window and mainly absorbed from the stomach and the upper part of the small intestine. Following administration of furosemide, the natriuretic effect rapidly disperses and is concealed before the next administration. This problematic aspect in furosemide therapy is mostly attributed to the natural homeostatic compensatory mechanisms. Lately, it has been demonstrated that the diuretic and natriuretic effects of furosemide can be significantly improved, following a continuous input (intravenous infusion) compared to immediate release DFs. Beside the narrow absorption window, this pharmacodynamic feature of the drug provides another rationale for the development of a GRDF for furosemide. 

The renal toxicity of ciclosporin has been described as being an adverse effect of the drug on the compensatory mechanisms of the kidney, without effects on proximal tubular function (urea and sodium reabsorption) (91). A rise in serum creatinine concentration may be adequate to identify acute-onset ciclosporin nephrotoxicity, but it is not suitable for identification of chronic, late-onset ciclosporin nephrotoxicity (92). 

This system is important in the excretion of acids in the urine, as is explained in the section on renal compensatory mechanisms. 

The compensatory mechanisms for metabolic alkalosis include both respiratory compensation and, if physiologically possible, renal compensation. 

The compensatory mechanisms respond to respiratory alkalosis in two stages. In the first stage, erythrocyte and tissue buffers provide H ions that consume a small amount of HCOT The second stage becomes operational in prolonged respiratory alkalosis and depends on the renal compensation as described for metabolic alkalosis (decreased reclamation of bicarbonate). 

In mixed respiratory and metabolic acidosis, there is a failure of compensation. The respiratory disorder prevents the compensatory decrease in PaC02 expected in the defense against metabolic acidosis. The metabolic disorder prevents the buffering and renal mechanisms from raising the bicarbonate concentration as expected in the defense against respiratory acidosis. In the absence of compensatory mechanisms, the pH decreases markedly. 

Hypoxia decreases resistance to blood flow in many vascular beds. This could be a compensatory mechanism to increase blood flow to the hypoxic region. In the coronary, cerebral, renal, and skeletal muscle circulations this hypoxic vasodilation is attenuated by glibenclamide, suggesting a role for K xp channels in the response (von Beckerath et al., 1991 Daut et al.,... 

Fluid or water overloading may occur when excessive thirst is induced by a test compound, inappropriately high intravenous infusion rates, cardiac failure, or failure of renal excretion to act as a compensatory mechanism. This may cause reductions of plasma sodium, protein, albumin, and osmolality values. The osmolality of a test solution for intravenous administration may affect fluid balance when the injection volumes are relatively large compared to the ECF volume of the animal (Michel... 

Diuretics are drugs that increase the rate of urine flow clinically useful diuretics also increase the rate of excretion of Na+ (natiiuresis) and an accompanying anion, usually CD. Most clinical applications of diuretics aim to reduce extracellular fluid volume by decreasing total-body NaCl content. Although continued administration of a diuretic causes a sustained net deficit in total-body Na+, the time course of natriuresis is finite because renal compensatory mechanisms bring Na+ excretion in line with Na+ intake, a phenomenon known as diuretic braking. Compensatory mechanisms include activation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone axis, decreased arterial blood pressure (which reduces pressure natriuresis), hypertrophy of renal epithelial cells, increased expression of renal epithelial transporters, and perhaps alterations in natriuretic hormones such as atrial natriuretic peptide. 

Patients with chronic parenchymal renal disease show a fall in RBF and GFR during treatment with NSAID, including aspirin . In chronic glomerulonephritis, afferent arteriolar dilatation may be a compensatory mechanism in the maintenance of filtration. A study of patients with systemic lupus erythematosus revealed an abnormal increase in basal PGE2 excretion consistent with the postulated means of compensation. In other aetiologies of renal insufficiency, including diabetes, hypertension and interstitial nephritis, there is acute worsening of renal function with NSAID " ... 

Patients with primary proximal tubular acidosis usually have stable serum HCO3 levels in spite of the reduced acid excretion. The compensatory mechanism is not known, but reduced endogenous acid production can probably be excluded. A more likely adaptation is the formation of additional bases at the expense of bone CaC03. Some patients with primary proximal acidosis present skeletal demineralization, reduced levels of CO3 in the hydroxyapatite crystals, and increased calcium losses in the feces. Patients with proximal renal acidosis are usually symptomless, and except in cases of acid overproduction, the prognosis is usually favorable. 

In chronic hypercapnia, the full compensatory mechanism is placed in gear. The central events are increased acid secretion by the kidney (ammonium plus titrable acid) and increased reabsorption of bicarbonate (HCO3). Indeed, the maximum renal reabsorption of bicarbonate rises with the increase in Pco2 levels in blood. 

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