Liver Disease: Liver Cirrhosis Pathophysiology Flashcards
Assessing Liver Function
§ There is no quantifiable way to determine severity
§ Usually a qualitative assessment by reviewing all labs and looking at
patterns of abnormalities
§ Important to determine if function is affected
§ Child-Pugh score is the most common severity index for cirrhosis
§ Always put assessment (labs, score etc.) into context based on history
and physical exam
Which of the following lab tests are used to measure liver synth fxn?
Biosynthetic Capabilities
Both album in and INR
Fully measure fxn of liver
AST does not measure fxn (for inflammation)
liver fxn: albumin, clotting factors § True measure of liver function § Albumin § Prothrombin time/INR § Synthetic reserves requires substantial impairment before changes are seen
§ Blood liver enzymes – Aspartate aminotransferase (AST) – Alanine aminotransferase (ALT) –Gama-glutamyl transpeptidases (GGT) – Alkaline phosphatases (ALP) § Bilirubin § Albumin § INR
Liver Function Tests (LFT)
LFT is a misnomer, these tests measure damage/inflammation but not function
§ LFT are often non-specific tests
§ Should not be used for diagnosis alone, need to consider patient history, physical exam and other investigations.
§ Consider that liver has enormous reserve, not sensitive to low levels of damage or dysfunction
§ LFT’s can not be used to directly determine doses for medications as they do not measure function (unlike renal function tests)
Ammonia
§ Ammonia is taken by the liver and converted to urea where it is excreted by kidneys.
§ Increased levels of ammonia can be seen with hepatocellular disease or portal hypertension
§ Accumulation of ammonia is associated with hepatic encephalopathy from hepatic cirrhosis
Normal range 17 – 41 µmol/L
Child Pugh Score
§ Classifies patients into mild, moderate or severe hepatic dysfunction
§ Add up scores to categorize into A, B or C
Determine if surgery should happen
A: 5-6 pts, good for surgical risk, 90% 1 yr survival
B: 7-9, moderate, 80%
C: 10-15. poor, 45%
what factors determine child pugh score
bilirubin albumin INR encephalopathy (none, medically controlled, poorly controlled) ascites
End Stage Liver Disease
§ Fibrosis
–Diffuse and irreversible
§ Parenchymal architecture of liver disrupted by interconnecting fibrous scars
–Vascular architecture is reorganized
§ Parenchymal nodules created by regeneration of hepatocytes
§ The stimuli for fibrous tissue deposition is unknown
§ Collagen deposition occurs in all parts of the lobule
§ Activated stellate cells (involved with storage of retinoids) may be the major source of collagen synthesis
§ Once they become activated, develop features of fibroblasts.
§ Fibrous tissue accumulation results in disruption of hepatic blood flow, resistance to portal blood flow and elevation of portal blood pressure
End Stage Liver Disease
pathophys
Kupffer cells specialized macrophages
Activated in fibrosis that produces a bunch of inflamm mediators, Cytokines
That may result in activate stellate cells resuling in collagen release
§ Once they become activated, develop features of fibroblasts.
§ Fibrous tissue accumulation results in disruption of hepatic blood flow, resistance to portal blood flow and elevation of portal blood pressure
Alcohol Effects on the Liver
§ Alcohol leads to 3 forms of liver disease:
–Hepatic steatosis
–Alcoholic hepatitis
–Cirrhosis
Hepatic Steatosis
§ Fatty liver, lipid droplets accumulate in hepatocytes
§ From chronic intake of alcohol (15-20 years of drinking)
§ Shunting of normal substrates away from catabolism and moved towards lipid biosynthesis, impaired assembly and secretion of lipoproteins
§ Initially there is little or no fibrosis
§ Reversible with abstinence from alcohol
§ LFT changes: mild elevation of bilirubin, ALP, GGT
GGT specific from alcohol abuse
Alcoholic Hepatitis
§ Associated with hepatocyte swelling and necrosis
Inflamm of liver Ongoing
§ Mallory bodies: hepatocytes with cytokeratin intermediate filaments and other proteins accumulated
Mallory bodies found in cytoplasm, leratin like filaments
- Filaments improtant for maintaining structure
They become damaged and other proteins accumulat
§ Increase in neutrophils which accumulate around degenerating liver cells, influx of inflammatory cells
§ Fibrosis is present
§ Symptoms can vary from no symptoms to fulminant hepatic failure
§ About 1/3 will develop cirrhosis with repeated bouts of alcohol
Alcoholic Hepatitis
liver function tests:
§ Increase in liver function tests:
–AST>ALT (>2 fold increase)
–GGT>ALP
•remember getting GGT if elevated ALP will determine hepatic source
•GGT may be >2.5 fold increase to ALP - often indicates alcohol abuse
§ Increase in bilirubin (both conjugated and unconjugated)
Alcoholic Cirrhosis
§ Alcoholic cirrhosis is the final form of liver damage seen with alcohol, it is irreversible
§ Liver becomes a shrunken, deformed organ
§ End-stage alcoholic cirrhosis looks very similar to viral hepatitis or other end stage liver disease
§ Women have a higher risk of alcoholic cirrhosis, as well hepatic damage occurs faster compared to men
§ Cirrhosis may develop without evidence of steatosis or alcoholic hepatitis beforehand
explain relationship b/w normal liver, steatosis, cirrhosis, hepatitis
normal liver can lead to steatosis, hepatitis
steatosis can lead to hepatitis with severe exposure
abstinence can reverse and hepatitis to steatosis
continued exposure of steatosis leads to cirrhosis
repeated attacks of hepatitis leads to cirrhosis
Alcohol Consumption and Risk
14 g of alcohol
About 5ounces of wine
§ Short term: Ingestion of up to 60-80 gm of alcohol (equal to ~6 beers or 8 oz of liquor) 1 – 3 days can produce a mild, reversible hepatic changes
such as fatty liver
§ Chronic: Intake of 60 - 80 gm/day or more daily for >10 years is associated with cirrhosis, these numbers are for men. In women, the risk has been as low as 20 gm/day
What is the safe amount of alcohol consumption?
In the absence of a clear understanding on the pathogenetic factors influencing liver damage, no safe upper limit can be proposed.
