Liver path general features Flashcards
What are the major primary diseases of the liver?
Viral hepatitis
Alcoholic liver disease
NAFLD (non-alcoholic fatty liver disease)
Hepatocellular carcinoma
Hepatic damage can also occur as secondary result of extra-hepatic diseases, including?
cardiac decompensation
Metastasis
Extrahepatic infections
How is the liver able to compensate for mild-moderate damage?
There is a large functional reserve
Are liver diseases typically acute or chronic?
Chronic (insidious)
Exception is acute hepatitis in viral hepatitis, and fulminant hepatitis
What are the typical cellular signs of liver pathology
Hepatocyte degeneration and intracellular accumulations
Hepatocyte necrosis and apoptosis
Inflammation
Fibrosis
Regeneration
How may a liver progress to failure?
Through massive parenchymal damage (fulminant hepatitis)
Or through repeated waves of damage over a long period of time (seen in chronic liver diseases)
What is the threshold for hepatocyte loss before the onset of liver failure?
80-90%
What is the mortality of liver failure without transplantation?
80%
What is the definition of acute liver failure?
Progression of liver damage to hepatic encephalopathy within 6 months
Does fulminant liver failure occur quicker than acute liver failure?
Yes
Fulminant failure is within 2 weeks, acute is within 6 months
What are the primary causes of acute liver failure?
Infection (hep viruses, CMV, yellow fever)
Drugs (paracetamol, isoniazid, halothane)
Toxins (mushroom toxin, tetrachloride)
Vascular (Budd-Chiari syndrome, veno-occlusive disease)
Other (alcohol, haemochromatosis, alpha1-anti-trypsin deficiency, Wilson’s disease, fatty liver of pregnancy)
Does the liver need to undergo overt necrosis to suffer liver failure?
No
Hepatocyte function can be viable but unable to perform normal function, as with tetracycline toxicity and acute fatty liver of pregnancy
What are the three categories of liver failures?
Acute
Chronic
Failure without overt necrosis
Name 6 clinical features of hepatic failure
Jaundice
Asterixis
Hypoalbuminaemia
Hyperammonaemia (contributes to encephalopathy)
Foetor hepaticus (from porto-systemic shunting)
Palmar erythema
Spider angiomas
What is the aetiology of palmar erythema and spider angiomas in liver failure?
Impaired oestrogen metabolism in the liver leading to hyperoestrogenaemia
Decreased inactivation of vasoactive endotoxins by the liver (palmar erythema)
What are some major causes of death in hepatic failure?
Hepatic encephalopathy
Hepatorenal syndrome
Hepatopulmonary syndrome
Describe the aetiology of coagulopathy in hepatic failure, and the consequence that has back on the liver
Impaired hepatocyte function leads to paucity of clotting factors
Gastrointestinal bleeding
Uptake of blood in intestines leads to further metabolic load
What is elevated in the blood to specifically cause hepatic encephalopathy?
Nitrogenous wastes, in the form of ammonia
How do astrocytes cause hepatic encephalopathy?
They clear the hyperammonaemia with the conversion of glutamate to glutamine
Excess glutamine in the brain causes an osmotic imbalance, resulting in net water shift into neurons -> cerebral oedema
What is hepatorenal syndrome?
Renal failure in patients with advanced chronic liver disease
What diagnosis would be suspected in a patient with pre-renal uraemia and liver failure?
Hepatorenal syndrome
T/F hepatorenal syndrome responds to fluid replacement
False
Is urea the best way to measure renal function on a background of liver failure/disease?
No; urea is synthesised in the liver
Creatine is better as it does not rely on the liver functioning correctly and better reflects only the kidneys
What leads to hepatorenal syndrome?
Decreased renal perfusion pressure due to systemic vasodilation
Activation of the renal sympathetic nervous system with vasoconstriction of the afferent renal arterioles
Increased synthesis of renal vasoactive mediators, which decrease GFR
RAAS system activation worsens renal vasoconstriction
What is hepatorenal syndrome type 1?
Rapidly progressive deterioration in circulatory and renal function
Median survival of <2 weeks
What is hepatorenal syndrome type 2?
Slow deterioration of circulation and renal function
Median survival of ~6 months
How do you treat hepatorenal syndrome?
IV albumin + vasoconstrictors (replenish depleted volume)
Haemodyalisis for support
Liver transplant will most likely be needed eventually
If a patient has liver failure, what complications need to be monitored for?
GI bleeding, esp oesophageal varices
Sepsis
Encephalopathy
Hypoglycaemia
Spontaneous bacterial peritonitis
What blood tests should be performed daily on a liver failure patient?
FBC, U&E, LFT + INR
What special consideration should be given to prescribing drugs to a liver failure patient?
Whether the drug has hepatic metabolism
What drugs should not be given to a liver failure patient?
Diuretics (^ risk of encephalopathy)
Hypoglycaemics (already at risk of hypoglycaemia)
Saline containing IV’s
Sedatives (confuse hepatic encphalopathy diagnosis)
Paracetamol, isoniazid, oestrogen, 6-mercaptopurine and methotrexate, salicylates, tetracycline
What characterises hepatopulmonary syndrome?
Tried of chronic liver disease, hypoxaemia, and intra-pulmonary vascular dilations (IVPDs)
How will a patient with hepatopulmonary syndrome appear when seated upright?
They will have dyspnoea and hypoxaemia (platypnea and orthodeoxia respectively)
What is thought to cause hepatopulmonary syndrome?
Increased hepatic production of, or reduced hepatic clearance of, vasodilators (esp NO)
What two processes lead to the symptoms of hepatopulmonary syndrome?
Vasodilation causes ventilation-perfusion mismatch (too much perfusion for the same ventilation)
Late in the syndrome there is high output failure (fast blood flow through capillaries lessens time in capillary for RBCs, worsening hypoxia)
What are some poor prognostic markers in liver failure/disease?
Grade III/IV encephalopathy (stupor, significant confusion/coma)
Albumin 40yrs
Late onset hepatic failure worse than fulminant failure
What characterises cirrhosis histologically?
Loss of normal hepatic structure throughout entire liver
Extensive fibrosis
Expanding regions of regeneration (gives it the distinctive nodular gross appearance)
What are main causes of cirrhosis?
Chronic alcohol abuse
NASH
Chronic infection (HBV/HCV)
Autoimmune disease
Haemachromatosis, alpha1 anti-trypsin deficiency, Wilson’s disease
Vascular (Budd-Chiari syndrome)
List the three central pathogenic processes of cirrhosis
Hepatocyte death
ECM deposition by myofibroblasts (converted from stellate cells)
Vascular reorganisation
Is cirrhosis always symptomatic?
No
40% of patients are asymptomatic until decompensation or simple disease progression
What are some signs found in cirrhosis patients?
Leuconychia, clubbing
Hyperdynamic circulation
Dupuytrens contractures
Spider naevi and other signs of portal HTN
Hepatomegaly (or small liver, in late disease)
Is coagulopathy a complication of cirrhosis?
Yes
Decreased production of clotting factors II, VII, IX and X cause ^ INR)
Also, if cholestasis present, decreased micelle entry into small intestine reduces vit K absorption with resulting lowering of clotting factor production
What are some decompensation events for cirrhosis?
Superimposed hepatic metabolic load (from systemic infection or GI haemorrhage)
Hepatopulmonary syndrome leading to hypoxia (^ stress)
T/F cirrhosis is a major risk factor for hepatocellular carcinoma
True
Must screen every 3-6 months in cirrhosis patients
How can cirrhosis be treated?
Transplant is the only cure
Treat causes (eg infection, alcohol etc)
Treat symptoms (eg support body systems)
How can hepatic encephalopathy be treated?
Lactulose (moves ammonia into gut lumen)
Antibiotics (lowers ammoniagenic bacteria populations in gut; Rifaximin)
