Cirrhosis Overview | Clinical Presentation



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 an alcoholic liver disease or subject to a viral attack for a long time like an HB V 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 our wives erotic 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 will 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 para sinusoidal space here's a pretty basic layout of the basic functional unit of the liver you've got the portal vein in the hepatic artery that combined into a sinusoid which then goes into the central vein and these are all aligned with hepatocyte right along these though you've also got a bile duct and all these three constitute a portal triad so the Paris sinusoidal space which literally means around the sinusoidal space and stellate cells are about here and usually in healthy tissue these guys's main function is to store vitamin A and are otherwise considered quiescent 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 stellate cells lose vitamin A proliferate and start secreting transforming growth factor beta 1 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 the fluid inside the pressure starts to build up leading to INTRUST sinusoidal 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 per Otoniel cavity that's why cirrhosis leads to excess proto neo fluid a condition called ascites and can result in complications like congestive 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 or 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 bay we 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 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 jerky hands when outstretched and is even more toxins build up eventually patients can progress to a coma also since the liver plays a big role in metabolizing estrogen into inactive metabolites that can be removed from the blood and excreted patients can also experience complications due to increased estrogen in the blood like gynecomastia spider angiomas and palmar erythema and since the liver usually conjugates bilirubin they'll 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 is not functioning right you can have a decreased amount of albumin in the blood or hypoalbuminemia 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 to recap the general symptoms of cirrhosis early on with a small amount of scarring in fibrosis we call it compensated cirrhosis meaning that the liver can still do a lot of its job in this case somebody with cirrhosis might not have any symptoms or they might have nonspecific symptoms like weight loss weakness or fatigue later on though with extensive scarring the liver progresses to decompensated cirrhosis and it can't function normally at this point a lot of the described symptoms start to develop like jaundice and paratus or itchy skin ascites hepatic encephalopathy which can lead to confusion and easy bruising from localization factors for diagnosis the gold standard is a liver biopsy which is taking a tiny sample of the liver tissue and examining it under a microscope common lab findings include elevated serum bilirubin as well as elevated liver enzymes like ass part 8 amino transferase or AST and alanine aminotransferase or alt where AST is usually more elevated than alt also alkaline phosphatase or ALP and gamma glue to mil transpeptidase or GG t can also be elevated and there might also be thrombocytopenia or low platelet count as to treatment generally the scarring in cirrhosis is irreversible so first of all it's important to prevent continued liver damage by identifying the underlying cause in treating that for example stopping alcohol consumption or antiviral treatment for those with hepatitis C with advanced cirrhosis though where the liver stops functioning a liver transplant might be needed all right as a quick recap cirrhosis is when inflammation and liver damage causes the liver to become fibrotic and develop scar tissue causes include things like excessive alcohol consumption or prolonged viral attack like from hepatitis B or hepatitis C virus over time as the liver becomes less functional symptoms like jaundice ascites easy bruising and hepatic encephalopathy develop diagnosis is often done with a biopsy or through lab tests and treatment for advanced cirrhosis is to treat the underlying cause but sometimes the liver transplants required you

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