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u/Fellainis_Elbows

Am I doing something wrong or do I just need to be more patient?
▲ 1 r/SourdoughStarter

Am I doing something wrong or do I just need to be more patient?

Have been following Grant Bakes 3 phase starter guide. Had my false rise on like day 3 and since then nothing but a few bubbles. I’m feeding 1:1:1 every 48 hours currently with warmed up tap water and wholewheat flour. At 24 hours after feeding there’s very minimal bubbles. It’s currently about 21C in my house. For the last few days I’ve been keeping it in the microwave next to a bowl of hot water to try and warm things up.

Picture is what it looks like today on day 21 at about 40hrs post the last feed.

u/Fellainis_Elbows — 1 day ago
▲ 62 r/IntensiveCare+1 crossposts

My understanding is the following:

  1. Hepatic fibrosis -> increased resistance to blood flow -> blood backs up into portal vessels​
  2. Increased shear stress on blood vessels in portal/splanchnic circulation -> NO production​
  3. Vasodilation everywhere (but splanchnic > systemic because more exposed to NO)​
  4. MAP maintained via compensatory vasoconstricting mechanisms which preferentially effect systemic vessels (less exposed to NO) -> renal hypoperfusion -> RAAS/ADH/sympathetic activation -> sodium & water retention & increased cardiac output with increased HR despite low SVR and MAP = "hyperdynamic" circulation

In the above model I can explain the production of ascites pretty easily. There’s increased pressure in the portal system and congestion of the liver and mesentery / intestines -> fluid leaks out of these due to an increased hydrostatic pressure gradient -> fluid collects in peritoneal space.

What I can’t explain very easily is peripheral oedema. Even though there’s increased total body water and sodium there is decreased SVR and MAP. Therefore I can’t explain this based on an increased hydrostatic pressure gradient forcing fluid out into the interstitium.

What about oncotic pressure you say? We all know cirrhotics produce less albumin and that albumin contributes to intravascular oncotic pressure preventing oedema… However, we also now know that that is bunk. See a whole heap of literature in the last 15 years starting with Levick and Mickel and Thomas Woodcock on the revised starling equation.

We know from studies on nephrotic syndrome (https://www.kidney-international.org/article/S0085-2538(15)55610-X/fulltext ) and malnutrition (https://pmc.ncbi.nlm.nih.gov/articles/PMC9014367/) that hypoalbuminaemia does NOT drive oedema or third spacing and that separate mechanisms are involved in these conditions. In patients with nephrotic syndrome and oedema for example the interstitial oncotic pressure actually drops in parallel to the intravascular oncotic pressure such that there’s no change in the gradient. Serum albumin often being low in oedematous states is correlation, not causation. 

What I’m left with is simply increased permeability. I think this might explain things. Cirrhotics have a baseline endotoxaemia + increased circulating NO which would plausibly increase fluid movement out into the interstitium by itself.

Does anyone know if there’s any literature that’s looked into this question or mechanism? I struggled to find anything with a quick search.

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u/Fellainis_Elbows — 23 days ago