Tubuloglomerular feedback mechanism

Fig. 12.1 Main structural components of the nephron. Note particularly how the terminal part of the loop of Henle passes within cellular distances of the afferent arteriole. This forms the anatomical basis for the tubuloglomerular feedback mechanism by which the nephron regulates the incoming blood flow in response to variations in the ionic composition of the fluid that leaves the loop of Henle.

A Dynamic Model of the Tubuloglomerular Feedback Mechanism, Am. J. Physiol. 258, F1448-F1459 (1990). 

Toward the end of the first week of continuous thmjr with a CA inhibitor, resistance develops to its diuretic ti feci. This is primarily due lo two factors. First, there s. marked reduction in the filtered load of HCOr because ib CA inhibitors produce both a 2O0f reduction in the Gfl via the tubuloglomerular feedback mechanism, and a Rste-tion in the plasma concentration of HCO3. When Iheit less HC0.3 present in the luminal fluid, there is less HCO reabsorption to inhibit. Second, the metabolic acklixsiscn ated by these diuretics provides a sufficient amouni it... 

Explain how the myogenic mechanism and tubuloglomerular feedback are responsible for autoregulation of renal blood flow... 

The macula densa, which is involved in tubuloglomerular feedback, is also a factor in the regulation of renin secretion. In fact, this mechanism involving the macula densa is thought to be important in the maintenance of arterial blood pressure under conditions of decreased blood volume. For example, a decrease in blood volume leads to a decrease in RBF, GFR, and filtrate flow through the distal tubule. The resulting decrease in the delivery of NaCl to the macula densa stimulates the secretion of renin. Increased formation of angiotensin II serves to increase MAP and maintain blood flow to the tissues. 

Increased delivery of salt to the TAL leads to activation of the macula densa and a reduction in glomerular filtration rate (GFR) by tubuloglomerular (TG) feedback. The mechanism of this feedback is secretion of adenosine by macula densa cells, which locally causes afferent arteriolar vasoconstriction. This vasoconstriction reduces GFR. Tubuloglomerular feedback-mediated reduction in GFR exacerbates the reduction that was initially caused by decreased cardiac output. Recent work with adenosine receptor antagonists (eg, rolofylline) has shown that it will soon be possible to circumvent this complication of diuretic therapy in heart failure patients. Using rolofylline with a diuretic will make it possible to produce an effective diuresis in patients with heart failure without causing renal decompensation. 

Na-i-K-i-2CI- (NKCC) cotransporter inhibitors, furosemideand bumetanide. NKCC modulation alters vasoconstrictorby a mechanism that does not involve tubuloglomerular feedback responses [259]... 

The result of the combination of myogenic mechanisms and tubuloglomerular feedback is that the net filtration pressure or Pccap is kept reasonably constant over a very wide range of systemic arterial pressures. It should be noted that renal blood flow and GFR change across this range of systemic pressures but to a significantly smaller extent than would be predicted if these autoregulatory mechanisms were not in place. 

There are several potential mechanisms of PG involvement in the pathogenesis of acute renal failure (ARF). Vascular factors are pre-eminent in the initiation and maintenance of acute renal failure. These include control of RBF, autoregulation, tubuloglomerular feedback, the glomerular capillary ultrafiltration coefficient (Kf), the no-reflow phenomenon (which is secondary to capillary endothelial injury and swelling), the renin-angiotensin system and endogenous vasoconstrictors (e.g. catecholamines). 

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