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In cirrhosis -- renal failure
In kaplan due to intense vasocontriction of afferent arteriole ..
In UW .. generalized vasodilation causes decrease TPR .. decrease renal perfusion ...
...... actually what happens ?? .. as both of them make sense ...
 

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They are both correct!

The statement decreased TPR leading to decreased renal blood flow is not correct physiologically. Because when you have decreased resistance you definitely have more flow.

However, the story in HRS as I guess, is that increased ATII has resulted in renal vasoconstriction yet a decrease in "total" peripheral vascular resistance due to activation of the SNS that has attempted to increase the cardiac output and caused a hyperdynamic circulation.

So probably both Kaplan and UW are correct here, but am not sure.
 

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HRS is the most advanced stage of the various pathophysiologic derangements that take place in patients with cirrhosis. The hallmark of HRS is intense renal vasoconstriction that starts at an early time point and progresses with worsening of the liver disease. The underlying mechanisms that are involved in HRS are incompletely understood but may include both increased vasoconstrictor and decreased vasodilator factors acting on the renal circulation. Type 2 HRS is gradually progressive and arises in association with the progression of cirrhosis, whereas type 1 is an acute deterioration in kidney function associated with severe renal vasoconstriction and failure of compensatory mechanisms that are responsible for maintenance of renal perfusion. Four interrelated pathways have been implicated in the pathophysiology of HRS. The possible impact of each one of these pathways on renal vasoconstriction and the development of HRS varies from one patient to the other. These pathways include:
  1. Peripheral arterial vasodilation with hyperdynamic circulation and subsequent renal vasoconstriction;
  2. Stimulation of the renal sympathetic nervous system (SNS);
  3. Cardiac dysfunction contributing to the circulatory derangements and renal hypoperfusion;
  4. Action of different cytokines and vasoactive mediators on the renal circulation and other vascular beds.
Peripheral Arterial Vasodilation
In the setting of liver dysfunction and portal hypertension, the effective circulating volume decreases secondary to (1) increase in splanchnic blood pooling as a result of increased resistance of blood flow through the cirrhotic liver and (2) vasodilation of the systemic and splanchnic circulation resulting from increased vasodilator production due to cytokine production. The low effective circulating volume unloads the high-pressure baroreceptors in the carotid body and aortic arch with subsequent compensatory activation of the SNS, the renin-angiotensin-aldosterone system (RAAS) and nonosmotic release of vasopressin. This results in a hyperdynamic circulation with increased cardiac output (CO), decreased systemic vascular resistance, hypotension, and vasoconstriction of the renal vessels. With cirrhosis progression, further splanchnic vasodilation occurs, creating a vicious cycle that favors more systemic vasodilation and subsequent renal vasoconstriction. Although this hypothesis provides a rational and simple explanation to the hemodynamic changes that take place in cirrhosis and HRS, it has not been tested in human studies. However, the markedly reduced systemic vascular resistance despite elevated norepinephrine, renin, and aldosterone levels is well documented and is compatible with peripheral vasodilation. Studies by Fernandez-Seara and others demonstrate that the degree of hepatic decompensation directly correlates with the degree of hyperdynamic circulation and inversely correlates with the arterial BP, with the most extreme hemodynamic changes noted in patients with HRS. Finally, the improvement in the hemodynamic and neurohormonal parameters and reversal of HRS with systemic vasoconstrictor administration (discussed below) provide additional support to the peripheral vasodilation role in renal hypoperfusion and vasoconstriction. It becomes sensible, then, to ask why renal vasoconstriction persists despite the presence of systemic vasodilation. It has been demonstrated that with liver disease progression and before the development of HRS, femoral artery blood flow decreases, whereas mesenteric blood flow continues to rise. Importantly, it was showed a correlation between the reduced femoral blood flow and the renal blood flow (RBF) in patients with decompensated cirrhosis, including patients with HRS. Similar correlation is also noted between the cerebral and the upper extremities blood flows and the RBF. In addition, studies in animal models and humans with cirrhosis consistently demonstrate that the splanchnic circulation is the main vascular bed responsible for the peripheral vasodilation, especially in advanced liver disease. These findings suggest that at an early stage, both the splanchnic and the peripheral circulations are vasodilated and contribute to the genesis of the hyperdynamic circulation. However, with cirrhosis progression, the splanchnic circulation becomes the primary vascular bed responsible for the maintenance of the hyperdynamic state, with subsequent stimulation of the compensatory vasoconstrictor mechanisms leading to vasoconstriction of extrasplanchnic vascular beds, including the kidney.

Reference: http://cjasn.asnjournals.org/cgi/content/full/1/5/1066
 

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Moreover, cirrhosis is a condition of high estrogen levels circulating into the bloodstream: defective liver function --> low levels of produced binding proteins --> estrogens are in their active forms, instead of being bound to proteins.

Estrogens cause vasodilation through mechanisms irrelevant to their classic interaction with the DNA, but instead through membrane endothelial receptors & NO.

This estrogen-induced vasodilation has been postulated to be responsible for palmar erythema, spider nevi, gynecomastia (spironolactone may also have a contribution, though) and even hepato-renal & hepato-pulmonary syndromes.

(The above is just a humble wannabe Ob-Gyn's contribution to a very fascinating, on pathophysiology grounds, topic :))
 

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What about the renal V.C

Moreover, cirrhosis is a condition of high estrogen levels circulating into the bloodstream: defective liver function --> low levels of produced binding proteins --> estrogens are in their active forms, instead of being bound to proteins.

Estrogens cause vasodilation through mechanisms irrelevant to their classic interaction with the DNA, but instead through membrane endothelial receptors & NO.

This estrogen-induced vasodilation has been postulated to be responsible for palmar erythema, spider nevi, gynecomastia (spironolactone may also have a contribution, though) and even hepato-renal & hepato-pulmonary syndromes.

(The above is just a humble wannabe Ob-Gyn's contribution to a very fascinating, on pathophysiology grounds, topic :))
Nice explanation that makes sense, but your theory did not explain the intense afferent arteriolar vasoconstriction seen in HRS!
 

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@laithbv

The kidneys recognize peripheral vasodilation as a reduction in effective circulating blood volume, i.e. the blood "pools" in the periphery (an extrapolation of this example would be neurogenic shock). So, the kidney initiates the appropriate responses to save as much fluid as possible.

This is how I have understood it (in an oversimplified version, I have to admit...). Any more professional contributions would be welcome!
 

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It's a physiologic puzzle

The pathophysiologic basis of HRS is not yet fully understood. The dilemma is that studies have consistently shown two observations:

  1. Renal vasoconstriction
  2. Systemic vascular vasodilation and decreased arterial pressure.
I agree with laithbv and the others that this is certainly counter-intuitive and does not go with our understanding of physiology. That's why theories (I repeat theories) have risen to explain this conflict.

One of the most acceptable theories is that the activated RAAS and SNS are responsible for the renal vasoconstriction yet the splanchnic circulation is resistant to that effect because of local NO production making the overall systemic resistance drops and hypotension results.

By the way, this conflict of decreased systemic resistance and renal vasoconstricion is not only seen in HRS but it is also puzzling physiologists studying Septic and Anaphylactic shock models.
 

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in cirrhosis there is a paradox of iintrahepatic decrease of No ( which represent the functional part of increased portal hypertension ) and increased extrahepatic NO ( --> systemic VD) so
* the increased No in systemic circulation --> Syst. VD --> decreased renal blood folw --> renal ischemia --> +RAAS ---> VC of afferent arteriole of kidney
* with more cirrhosis ( Note that HRS occurs with very late cirrhosis ) --> more paraox of decreaed intrahepatic No but increased extrahepatic NO ---> ++++ VD of systemic circulation ---> ++++++ VC of afferent arteriloe of glomeruli --- > decreased GFR --- > prerenal renal faliure
 
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