Liver path general features

Question 1

What are the major primary diseases of the liver?

Answer 1

Viral hepatitis

Alcoholic liver disease

NAFLD (non-alcoholic fatty liver disease)

Hepatocellular carcinoma

Question 2

Hepatic damage can also occur as secondary result of extra-hepatic diseases, including?

Answer 2

cardiac decompensation

Metastasis

Extrahepatic infections

Question 3

How is the liver able to compensate for mild-moderate damage?

Answer 3

There is a large functional reserve

Question 4

Are liver diseases typically acute or chronic?

Answer 4

Chronic (insidious)

Exception is acute hepatitis in viral hepatitis, and fulminant hepatitis

Question 5

What are the typical cellular signs of liver pathology

Answer 5

Hepatocyte degeneration and intracellular accumulations

Hepatocyte necrosis and apoptosis

Inflammation

Fibrosis

Regeneration

Question 6

How may a liver progress to failure?

Answer 6

Through massive parenchymal damage (fulminant hepatitis)

Or through repeated waves of damage over a long period of time (seen in chronic liver diseases)

Question 7

What is the threshold for hepatocyte loss before the onset of liver failure?

Answer 7

80-90%

Question 8

What is the mortality of liver failure without transplantation?

Answer 8

80%

Question 9

What is the definition of acute liver failure?

Answer 9

Progression of liver damage to hepatic encephalopathy within 6 months

Question 10

Does fulminant liver failure occur quicker than acute liver failure?

Answer 10

Yes

Fulminant failure is within 2 weeks, acute is within 6 months

Question 11

What are the primary causes of acute liver failure?

Answer 11

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)

Question 12

Does the liver need to undergo overt necrosis to suffer liver failure?

Answer 12

No

Hepatocyte function can be viable but unable to perform normal function, as with tetracycline toxicity and acute fatty liver of pregnancy

Question 13

What are the three categories of liver failures?

Answer 13

Acute

Chronic

Failure without overt necrosis

Question 14

Name 6 clinical features of hepatic failure

Answer 14

Jaundice

Asterixis

Hypoalbuminaemia

Hyperammonaemia (contributes to encephalopathy)

Foetor hepaticus (from porto-systemic shunting)

Palmar erythema

Spider angiomas

Question 15

What is the aetiology of palmar erythema and spider angiomas in liver failure?

Answer 15

Impaired oestrogen metabolism in the liver leading to hyperoestrogenaemia

Decreased inactivation of vasoactive endotoxins by the liver (palmar erythema)

Question 16

What are some major causes of death in hepatic failure?

Answer 16

Hepatic encephalopathy

Hepatorenal syndrome

Hepatopulmonary syndrome

Question 17

Describe the aetiology of coagulopathy in hepatic failure, and the consequence that has back on the liver

Answer 17

Impaired hepatocyte function leads to paucity of clotting factors

Gastrointestinal bleeding

Uptake of blood in intestines leads to further metabolic load

Question 18

What is elevated in the blood to specifically cause hepatic encephalopathy?

Answer 18

Nitrogenous wastes, in the form of ammonia

Question 19

How do astrocytes cause hepatic encephalopathy?

Answer 19

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

Question 20

What is hepatorenal syndrome?

Answer 20

Renal failure in patients with advanced chronic liver disease

Question 21

What diagnosis would be suspected in a patient with pre-renal uraemia and liver failure?

Answer 21

Hepatorenal syndrome

Question 22

T/F hepatorenal syndrome responds to fluid replacement

Answer 22

False

Question 23

Is urea the best way to measure renal function on a background of liver failure/disease?

Answer 23

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

Question 24

What leads to hepatorenal syndrome?

Answer 24

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

Question 25

What is hepatorenal syndrome type 1?

Answer 25

Rapidly progressive deterioration in circulatory and renal function Median survival of <2 weeks

Question 26

What is hepatorenal syndrome type 2?

Answer 26

Slow deterioration of circulation and renal function Median survival of ~6 months

Question 27

How do you treat hepatorenal syndrome?

Answer 27

IV albumin + vasoconstrictors (replenish depleted volume) Haemodyalisis for support Liver transplant will most likely be needed eventually

Question 28

If a patient has liver failure, what complications need to be monitored for?

Answer 28

GI bleeding, esp oesophageal varices Sepsis Encephalopathy Hypoglycaemia Spontaneous bacterial peritonitis

Question 29

What blood tests should be performed daily on a liver failure patient?

Answer 29

FBC, U&E, LFT + INR

Question 30

What special consideration should be given to prescribing drugs to a liver failure patient?

Answer 30

Whether the drug has hepatic metabolism

Question 31

What drugs should not be given to a liver failure patient?

Answer 31

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

Question 32

What characterises hepatopulmonary syndrome?

Answer 32

Tried of chronic liver disease, hypoxaemia, and intra-pulmonary vascular dilations (IVPDs)

Question 33

How will a patient with hepatopulmonary syndrome appear when seated upright?

Answer 33

They will have dyspnoea and hypoxaemia (platypnea and orthodeoxia respectively)

Question 34

What is thought to cause hepatopulmonary syndrome?

Answer 34

Increased hepatic production of, or reduced hepatic clearance of, vasodilators (esp NO)

Question 35

What two processes lead to the symptoms of hepatopulmonary syndrome?

Answer 35

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)

Question 36

What are some poor prognostic markers in liver failure/disease?

Answer 36

Grade III/IV encephalopathy (stupor, significant confusion/coma) Albumin 40yrs Late onset hepatic failure worse than fulminant failure

Question 37

What characterises cirrhosis histologically?

Answer 37

Loss of normal hepatic structure throughout entire liver Extensive fibrosis Expanding regions of regeneration (gives it the distinctive nodular gross appearance)

Question 38

What are main causes of cirrhosis?

Answer 38

Chronic alcohol abuse NASH Chronic infection (HBV/HCV) Autoimmune disease Haemachromatosis, alpha1 anti-trypsin deficiency, Wilson's disease Vascular (Budd-Chiari syndrome)

Question 39

List the three central pathogenic processes of cirrhosis

Answer 39

Hepatocyte death ECM deposition by myofibroblasts (converted from stellate cells) Vascular reorganisation

Question 40

Is cirrhosis always symptomatic?

Answer 40

No 40% of patients are asymptomatic until decompensation or simple disease progression

Question 41

What are some signs found in cirrhosis patients?

Answer 41

Leuconychia, clubbing Hyperdynamic circulation Dupuytrens contractures Spider naevi and other signs of portal HTN Hepatomegaly (or small liver, in late disease)

Question 42

Is coagulopathy a complication of cirrhosis?

Answer 42

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

Question 43

What are some decompensation events for cirrhosis?

Answer 43

Superimposed hepatic metabolic load (from systemic infection or GI haemorrhage) Hepatopulmonary syndrome leading to hypoxia (^ stress)

Question 44

T/F cirrhosis is a major risk factor for hepatocellular carcinoma

Answer 44

True Must screen every 3-6 months in cirrhosis patients

Question 45

How can cirrhosis be treated?

Answer 45

Transplant is the only cure Treat causes (eg infection, alcohol etc) Treat symptoms (eg support body systems)

Question 46

How can hepatic encephalopathy be treated?

Answer 46

Lactulose (moves ammonia into gut lumen) Antibiotics (lowers ammoniagenic bacteria populations in gut; Rifaximin)