I was hoping I could ask you a few questions. I’m finding there is a lottttt of contradictory information.
- According to starling forces, decreased plasma oncotic pressure should increase GFR, but according to nephrotic syndrome, decreased albumin will cause edema and overall decrease GFR. Which one should I believe?
- In general, it’s said that AT2 at low levels dilates the afferent arteriole to increase GFR, but at high level it constricts both efferent and afferent to decrease GFR. However, the SNS, which stimulates renin, constricts all arterioles in the body as well as activates the RAAS system. How does that work? Is the SNS more immediate until the aldosterone system is ready to say okay go ahead and dilate the afferent I’m ready to take up the water anyway?
- This is a very basic question but sometimes I have moments of self doubt and this is one of them: So we always say edema is fluid buildup in ISF due to increased hydrostatic or decreased oncotic pressure (like nephritic syndrome hypoalbumineia) right? So why does fluid build up in ISF as opposed to go inside the cell where I guess technically there is more stuff to pull it in?
- How does K suppress ammonia genesis?
Thank you very much!
Let’s take these one by one,
Nephrotic syndrome and GFR. Don’t connect those neurons. Proteinuria does not cause an immediate and hemodynamic change in GFR that is clinically meaningful. Yes, you are right that lower oncotic pressure should increase GFR, but those increases in GFR will be trimmed by tubuloglomerular feedback so that in the end there is not a meaningful change in GFR. Likewise the nephrotic syndrome will cause fluid to leak from the blood vessels decreasing effective circulating volume lowering renal plasma flow. However, once again these changes in volume are small enough that the kidney easily compensates with changes in AT2, PGE, filtration fraction, etc so that GFR remains stable.
Over a long time, proteinuria causes chronic kidney disease and decreases renal function, but not by the mechanisms you described.
Of note the model you are talking about with nephrotic syndrome causing fluid to leave the blood vessels and that resulting in decreased perfusion of the kidney is a model called underfill hypothesis of edema in nephrotic syndrome. Most nephrologists now ascribe by the overfill hypothesis which states that the primary abnormality is not loss of fluid from the capillaries from the decreased albumin, but increased sodium absorption by the diseased kidney. This results in volume overload and that causes the edema.
As I understand it angiotensin is only a vasoconstrictor. The proximal tubule is dilated by prostaglandin E. In volume depletion there is release of renin which activates angiotensin 2 (with help of angiotensin converting enzyme). Angiotensin 2 vasoconstricts both the afferent arteriole and efferent arteriole. But since the afferent arteriole is so much bigger to begin with, after the angiotensin 2 induced vasoconstriction the resistance in the afferent arteriole is less than the resistance in the efferent arteriole, this serves to increase the intraglomerular pressure, forcing more plasma through the glomerular slit membranes and increasing the filtration fraction and maintaining GFR in the face of volume depletion.
And yes the SNS is more immediate and the renin angiotensin aldosterone system is a bit slower.
Where fluid builds up depends on what is being altered. In nephrotic syndrome, the (underfill) theory states (I’m an overfill believer) that decreased plasma albumin lowers the oncotic pressure drawing fluid from the interstium back into the capillaries at the venous end. This means more of the fluid remains in the interstium leading to edema. The oncotic agent of note here is albumin which determines the flux of fluid between the interstitial and plasma compartment.
In order to shift fluid between the intracellular and extracellular compartments you would need to change sodium and potassium which are the chief osmotically active particles of interest between those two compartments.
Hyperkalemia causes potassium to shift into the cells. To maintain electroneutrality hydrogen leaves the cell. One cation in, one cation out. The loss of hydrogen ions makes the cell alkalotic. This rise in pH tricks the proximal tubule cell into believing the entire body is suffering from metabolic alkalosis and since ammonia generation is used to increase hydrogen excretion, and correct metabolic acidosis, metabolic alkalosis shuts down ammonia generation.