define erythema

when cells are injured or damaged, and die off, usually that dead tissue, that was previously full of living cells, becomes fibrotic, meaning it becomes thickened with heaps and heaps of protein and forms scar tissue. so, when your liver is constantly forced to process alcohol, like in alcoholic liver disease, or subject to a viral attack for a long time, like in hbv, or anything else that causes a long term, or chronic, state of liver cell, or hepatocyte, destruction and inflammation, your liver can become seriously scarred and damaged to the point where it’s no longer reversible,

at which point it becomes fibrotic, and, in the liver, we call this process cirrhosis. because it’s usually irreversible, cirrhosis is often referred to as “end -stage” or “late-stage” liver damage. when liver cells are injured, they start to come together and form what are called regenerative nodules. you can think of these as colonies of living liver cells. and these are one of the classic signs of cirrhosis, and are why a cirrhotic liver is more bumpy, as opposed to a smooth, healthy liver.

also, with cirrhotic liver tissue, you’ll see that, in between these clumps of cells, or nodules, is fibrotic tissue and collagen. here’s a classic histology image of cirrhotic tissue, this clump of cells in the middle is the regenerative nodule, and these blue stains surrounding it are the bands of protein from the process of fibrosis. if we zoom out a bit and look at it with the naked eye, we’ll again see these nodules, which have fibrotic protein bands in between. alright, but how do these bands of fibrotic tissue form though?

well, fibrosis is a process mediated by these special cells called stellate cells, that sit between the sinusoid and hepatocyte, known as the perisinusoidal space. here’s a pretty basic layout of the basic functional unit of the liver, you’ve got the portal vein and the hepatic artery that combine into a sinusoid, which then goes into the central vein, and these are all lined with hepatocytes, right? along with these though, you’ve also got a bile duct, and all these three constitute a portal triad.

so the perisinusoidal space, which literally means “around the sinusoidal space”, and stellate cells are about here. and usually, in healthy tissue, these guys’ main function is to store vitamin a, and are, otherwise, consideredquiescent, or sort of dormant. when the hepatocytes are injured though, they secrete paracrine factors that “activate” and sort of change the stellate cells. when activated, these stellatecells lose vitamin a,

proliferate, and start secreting secreting transforming growth factor beta1, or tgf-beta, which then causes them to produce collagen, which is the main ingredient in extracellular matrix, fibrosis, and then scar tissue. as this fibrotic tissue builds up, it starts to compress the central veins and sinusoids. it’s thought that in a healthy,normal state, these stellate cells play key roles in the natural wound-healing process,

but when the liver cells are constantly injured, the stellate cells are constantly activated, and so, they constantly produce collagen and factors that lead to fibrosis. and this is when complications due to cirrhosis start to crop up. as those central veins and sinusoids become compressed and push on thefluid inside, their pressure starts to build up, leading to intrasinusoidal, or sometimes called, portal hypertension, which is this higher pressure in the portal veins.

higher portal vein pressure means that fluid in the blood vessels is more likely to get pushed into tissues, and across tissues into large open spaces like the peritoneal cavity. that’s why cirrhosis leads to excessperitoneal fluid, a condition called ascites, and can result in complications likecongestive splenomegaly and hypersplenism, where the spleen becomes enlarged because all this fluid and blood can’t get into the liver, and backs up into the spleen instead. in the same way, your circulatory system starts diverting blood away from the liver because of the high liver pressures, and this is known as a portosystemic shunt.

and this happens because blood flow follows the path of least resistance and, basically, shunts away from the portal system and towards the systemic system of circulation. though not fully understood, these changes in portal flow ultimately trigger renal vasoconstriction, so increased resistance in the renal circulation, which decreases blood flow through the kidneys, leading to decreased filtration, and hepatorenal failure, where kidney failure follows liver failure.

the fibrotic tissue, pressure buildup, and diversion of blood from the hepatic circulation essentially reduces the number of functional sinusoidal veins, and the number of functional portal triads in general. as you have less and less of these basic liver functional units, your liver becomes less and less able to do its job of detoxification, right? when the liver isn’t detoxifying the blood, these toxins can get into the brain and start causing mental deficits, a condition known as hepatic encephalopathy. although there are several neurotoxins

that are thought to contribute to the development of these mental changes, the best understood factor is ammonia in the blood, which is produced mainly in the gastrointestinal tract. usually, the liver plays a huge role in removing ammonia, and stopping it from going into the systemic circulation. as the liver becomes more damaged, these, and other toxins, get into the brain, and patients might develop asterixis, where they have tremoring or jerkyhands when outstretched and, as even more toxins build up,

eventually patients can progress to a coma. also, since the liver plays a big role in metabolising oestrogen into inactive metabolites that can be removed from the blood and excreted, patients can also experience complications due to increased oestrogen in the blood, like gynaecomastia, spider angiomata, and palmar erythema. and, since the liver usually conjugates bilirubin, there will be increased unconjugated bilirubin in the blood from a less-functional liver, and that can lead to jaundice.

another important job of the liver is producing albumin. so, again, if the liver’s not functioning right, you can have a decreased amount of albumin in the blood, or hypoalbuminaemia. finally, the liver helps in making clotting factors or proteins that help coagulate your blood, so when you aren’t producing these coagulation factors, you can develop issues related to your ability to coagulate blood, which you need in order to stop blood loss after an injury, right?

so, at this point, it’s pretty clear that when your hepatocytes get injured to the point of no return, and start to form permanent scar tissue, and your liver becomes cirrhotic, there can be a lot of potential complications that can follow.