Liver general Flashcards
Functions of the liver
Glucose and fat metabolism
Detoxification and excretion
Protein synthesis
Defence against infection (reticulo-endothelial system)
Give examples of chemicals in the body which are detoxified and excreted
Biilirubin
Ammonia
Drugs/hormones/pollutants
Example of proteins synthesised by the liver
Albumin
Clotting factors
Types of liver injury
Acute
Chronic
What can result from acute liver injury
Recovery
Liver failure
Acute causes of liver failure
Viral (A, B, EBV) Drugs, Alcohol Vascular Obstruction Congestion
Chronic causes of liver failure
Recovery
Cirrhosis
Liver failure (varies, hepatoma)
Presentation of acute liver injury
Malaise, nausea, anorexia
Occasionally jaundice (doesn’t occur with everyone)
Rare:
-Confusion (encephalopathy)
-Bleeding
-Liver pain
-Hypoglycaemia (since liver breaks down glycogen to glucose, also the liver is the bodies major glucose store)
Presentation of chronic liver injury
Ascites Oedema (varices) Malaise Anorexia Wasting Easy bruising (since the liver produces clotting factors) Itching Hepatomegaly Abnormal LFTs Rare = Jaundice, Confusion
What are ascites?
Fluid accumulation in the peritoneal cavity
Examples of Liver Function Tests (LFTs)
Serum albumin
Bilirubin
Prothrombin time
Examples of liver biochemistry tests - is this a types of liver function test?
Liver biochemistry tests give NO index of liver function:
Aminotransferases
Alkaline Phosphate
In acute liver disease, what is expected from initial albumin levels?
May be normal
Low albumin is a bad prognostic sign
In LFTs, is bilirubin normally all conjugated or unconjugated?
All unconjugated
What can cause prolonged prothrombin time and what can it be a marker of?
Marker of synthetic function.
Sensitive indicator due to its short half-life for both acute and chronic liver disease.
Longer P time can result from vitamin K deficiency.
What is effect of biliary obstruction on Prothrombin time?
Biliary obstruction leads to low concentration of bile salts
Results in poor absorption of vitamin K and thus deficiency in vitamin K means reduced coagulation and longer prothrombin time
Give examples of amino-transferases that can be measured to assess liver biochemistry
Where are amino-transferases found?
Enzymes are found in hepatocytes and leak into blood with liver cell damage. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT)
Which aminotransferase is more specific to the liver?
ALT - Alanine Aminotransferase
Rise only occurs in liver disease
AST also present in heart, muscle, kidney and brain
In what other cases are Aspartate aminotransferases high, other than liver damage?
Hepatic necrosis
Myocardial infarction
Muscle injury
Congestive cardiac failure
What colour is bilirubin?
Yellow (contributes to colour of bile)
What are bile pigments formed from
Haem portion of Hb when old/damaged erythrocytes are broken down in the spleen and liver
What is the predominant bile pigment?
Bilirubin
What cells break down old or damaged erythrocytes and where are these cell found?
Macrophages
Spleen, bone marrow, liver (Kupffer cells here)
When erythrocytes are ingested by macrophages, what are they initially broken into?
Haem and globin
What is globin broken down into
Amino acids which can be used to generate new erythrocytes in the bone marrow
What is haem broken down into
Biliverdin
Fe2+ (transported to bone marrow to be implemented into new erythrocytes by transporter transferrin)
CO
What happens to biliverdin from haem breakdown?
Biliverdin is reduced by biliverdin reductase into UNCONJUGATED BILIRUBIN (toxic and must be secreted)
Why is unconjugated bilirubin bound to albumin in the blood
Lipid soluble and thus insoluble in blood
Must be transported bound to albumin to the liver
What happens to unconjugated bilirubin when it reaches the liver
GLUCURONIDATION
In liver, unconjugated bilirubin undergoes the addition of a glucuronic acid to make it soluble to be excreted under the action of UDP Glucuronyl Transferase, which converts it to CONJUGATED bilirubin
What enzyme converts unconjugated bilirubin to conjugated bilirubin
UDP Glucuronyl Transferase
In what condition do you have a deficiency in UDP Glucuronyl transferase and what is the result of this?
Gilbert’s syndrome
Raised unconjugated bilirubin
What happened to conjugated bilirubin once it enters the small intestine
Travels until it reaches the Ileum or beginning of colon, where it is reduced under the action of intestinal bacteria to form Urobilinogen
How is Urobilinogen formed
Conjugated bilirubin undergoes hydrolysis reaction under the action of intestinal bacteria, reducing it to form urobilinogen
(glucuronic acid group is removed)
What happens to urobilinogen once formed
10% is reabsorbed into the blood and bound to albumin (as is lipid soluble) and transported back to the liver.
90% remaining is oxidised by a different type of intestinal bacteria to form stercobilin
What happens to the 10% of urobilinogen that is transported back to the liver
Urobilinogen oxidised to urobilin
Here it is either recycled into bile or transported into the kidneys where it is excreted in urine - responsible for yellowish colour of urine
What happens to stercobilin
Excreted into faeces - responsible for the brownish colour
Types of jaundice
Unconjugated aka Pre-hepatic
Conjugated (Hepatic and Post-hepatic) aka Cholestatic
What causes the yellow discolouration of the skin in jaundice
Raised serum bilirubin
Give examples of Unconjugated or pre-hepatic causes of jaundice
Gilberts syndrome (deficiency in UDP Glucuronyl transferase) Haemolysis
Give examples of causes of (Conjugated/Cholestatic) Hepatic jaundice
Liver disease: Hepatitis -Viral (A, B, C, EBV) -Drug -Immune -Alcohol Ischaemia Neoplasm Congestion (congestive heart failure)
What is EBV
Epstein–Barr virus
Herpes simplex virus
Causes of post-hepatic jaundice
Bile duct obstruction due to: Gall-stone in Bile Duct Gall-stone in gallbladder/cystic duct pressing on the Common Bile) - Mirizzi syndrome Stricture Blocked stent
Describe presentation of Pre-hepatic jaundice
Urine = Normal
Stools = Normal
Itching = No
Liver tests = normal
Describe presentation of Cholestatic (hepatic or post-hepatic) jaundice
Urine = dark
Stools = may be pale
Itching = maybe
Liver tests = Abnormal
Useful questions for diagnosis jaundice
Dark urine, pale stool, itching? (if yes then likely cholestatic, not pre-hepatic) Symptoms? Past History? Drug Hx Social Hx
Jaundice: What symptoms would you ask about?
Biliary pain (right upper abdomen that radiates to shoulder)
Rigors
Abdomen swelling
Weight loss
Jaundice: What past history topics would you ask about?
Biliary disease/intervention? Malignancy? Heart failure? Blood products? Autoimmune disease?
What topics of social history would you ask in jaundice/liver disease
Alcohol? Potential Hepatitis contact: -Irregular sex? -IV drug use? -Exotic travel?
Diagnostic tests of liver
Liver enzymes - very high AST/ALT suggests liver disease
Biliary obstruction - 90% have dilated intrahepatic bile ducts on ultrasound
What is a hepatocellular carcinoma
cancer of the hepatocyte
Hepatocellular carcinoma clinical presentation
Fever, malaise, weight loss
Right upper quadrant pain, jaundice (late)
Hepatomegaly, ascites
Hepatocellular carcinoma aetiology
Hep B and C, Aflatoxin, alcohol, haemochromotosis, cirrhosis and anabolic steroids
Hepatocellular carcinoma epidemiology
90% of primary liver cancers (however 90% of cancer in the liver is a result of metastasis)
Hepatocellular carcinoma diagnosis
CT and biopsy
Hepatocellular carcinoma treatment
Surgery to resect individual tumours.
Liver transplant if multiple
Define liver failure
Loss of the livers ability to regenerate or repair
Types of liver failure
Fulminant hepatic failure
Late-onset hepatic failure
Chronic decompensated hepatic failure
Liver failure clinical presentation
Hepatic encephalopathy Abnormal bleeding Ascites Jaundice Mental state shows drowsiness and confusion, due to cerebral oedema
What are the differences between the types of liver failure
Time of liver failure relative to illness:
Fulminant hepatic failure = within 8 weeks of onset of underlying illness
Late-onset hepatic failure = 8-26 wks since onset of underlying illness
Chronic decompensated hepatic failure = latent period >6 months
Liver failure pathophysiology
Depends on aetiology.
Generally:
the destruction of hepatocytes,
the development of fibrosis in response to chronic inflammation,
the destruction of the architecture of the nodules of the liver removes the ability of the liver to adequately perform functions, repair and regenerate
Liver failure aetiology
Various: Toxins Infections Neoplastic e.g. Hepatocellular carcinoma Metabolic Others e.g. Acute fatty liver of pregnancy, ischaemia, autoimmune liver disease
Liver failure aetiology examples of toxins
Alcohol
Paracetamol poisoning
Liver failure aetiology examples of infections
Viral hepatitis
Epstein-Barr virus
CMV
Liver failure aetiology examples of Metabolic causes
Wilsons
A1AT deficiency
Haemochromatosis
Liver failure epidemiology
1/100,000
Paracetamol poisoning most common cause in acute liver failure
Liver failure diagnosis
Raised bilirubin Glucose low (no gluconeogenesis)
Liver failure treatment in more severe cases
Transplant
Complications of liver failure
Infection
Haemorrhage
(Hypoglycaemia)
