Liver Flashcards
What are the functions of the liver?
Glucose + fat metabolism
Detoxification + excretion
Bilirubin
Ammonia
Drugs/hormones/pollutants
Protein synthesis
Albumin
Clotting factors – vitamin K
Defence against infection
What is the anatomy of the liver?
4 lobes - RIGHT, LEFT, CAUDATE + QUADRATE
Receives blood from the hepatic artery and portal vein.
Blood leaves through the hepatic vein.
Made up of repeating identical cells
2 sources of blood entering it: hepatic artery and the portal vein
Hepatic artery arises from the celiac artery so shares its BS with the upper bowel. It supplies all of the bile with oxygenated blood + some of the liver. The portal vein supplies all of the liver with blood that has drained from the bowel wall (therefore allows liver to process nutritional components from bowel) - partially deox as already has given some to bowel
What is bile?
Formed in the liver
Stored + concentrated in the gallbladder
Gallbladder is stimulated to contract + release stored bile by cholecystokinin (CCK)
This is released upon detection of food (fats) in stomach
Bile aids emulsification + digestion of fats
Contains
Cholesterol
Bile pigments - from broken down Hb
Phospholipids
What are the different LFTs?
Albumin = protein made by the liver, marker of function (useful for seeing severity of chronic liver disease. In acute disease, levels may be normal) IF LOW = OEDEMA
Bilirubin - raised = obstruction within biliary system (e.g. gallstone/pancreatic tumour pressing against bile ducts). But remember could also be raised by increased production in the first place.
Prothrombin time = how long does it take the blood to clot (to clot blood needs vitamin K which is made by the liver so without it time is prolonged). Often converted into INR
Alkaline phosphatase (ALP) - non-specific. Abnormal = liver or bone probs. Raised = consistent w biliary obstruction. Aminotransferases (Alanine aminotransferase (ALT) + aspartate aminotransferase (AST)) - markers of hepatocellular injury GGT - don’t worry about too much. Mainly used to confirm a raised ALP is due to biliary origin (is more fluctuating so not as reliable)
Albumin helps transport things in the blood that are not soluble in water, + it helps keep fluid in the correct place in the body. Low albumin= oedema , low protein so fluid leaks out
INR is the same as PT but expressed as a ratio
Raised alkaline phosphatase can also be caused by liver or bone malignancy, primary biliary cirrhosis, Paget’s disease of the bone and many other things.
In patients with cholestasis (e.g., due to gallstones), ALT and AST can increase slightly, with a higher rise in ALP (“an obstructive picture”).
If ALT and AST are high compared with the ALP level, this is more indicative of a problem inside the liver with hepatocellular injury (“a hepatitic picture”).
GGT enzyme produced by both damaged and proliferative bile duct cells.
also raised by binge drinking for example
What are bile pigments?
Bile pigments = substances formed from haem when old/damaged erythrocytes are broken down by macrophages (specifically KUPFFER CELLS) in the spleen/liver
What is jaundice?
Pre-hepatic = excess breakdown of Hb -\> increased unconjugated bilirubin (caused by EXCESS HAEMOLYSIS) Hepatic = failure of hepatocytes to take up, metabolise or excrete bilirubin Post-hepatic = obstruction of biliary system
In pre-hepatic conjugated bilirubin is still made + excreted normally so you have normal wee + poo
Causes:
Maleria
Sickle cell anaemia
Haemolytic disease of the newborn
Gilberts syndrome
Hepatic has raised conjugated + unconjugated
Hepatic causes:
Viral hepatitis
Drugs
Alcohol
Cirrhosis
Conjugated bilirubin can’t be got rid of so builds up. Absent urobilinogen
Pruritis as there are bile salts in circulation
Post-hepatic causes:
Gallstones
Pancreatitis (head of the pancreas blocks CBD)
V high AST/ALT suggests liver disease
What are the signs and symptoms of jaundice?
What is Charcot’s triad?
What are gallstones?
Biliary colic = Pain associated with the temporary obstruction of the cystic/common bile duct by a stone migrating from the gallbladder (no signs of cystic inflammation). When it falls back into the gallbladder symptoms resolve.
Cholelithiasis = formation of gallstones
Gallstone formation risk factors? 4Fs: Fat, Fertile, Forty, Female, Fhx
Colicky RUQ pain - worse after eating large/fatty meals (may radiate to epigastrum + back)
Can be assoc w N&V
Fat entering the digestive system causes cholecystokinin (CCK) secretion from the duodenum. CCK triggers contraction of the gallbladder, which leads to biliary colic. Patients with gallstones and biliary colic are advised to avoid fatty foods to prevent CCK release and gallbladder contraction.
Most gallstones are made of cholesterol. Can be asx
What is cholecystitis?
Gallstone is blocking the cystic duct -> bile builds up -> gallbladder becomes distended -> vascular supply decreases -> inflammation
Severe RUQ pain
Fever + fatigue
+ve Murphy’s sign = severe pain on deep inhalation when examiners hand is pressed into RUQ
What is cholangitis?
Prolonged common bile duct blockage -> bile does not flush out the tubes so bacteria can climb up the GI tract -> biliary tree infection
As bile cannot enter GI tract -> obstructive jaundice
Severe RUQ pain w/ fever (rigors) + yellowing skin
May present as septic (+ have some pancreatitis)
How do you investigate biliary disease?
TO SEE IF CHOLECYSTITIS/CHOLANGITIS:
FBC + CRP - signs of an inflammatory response is suggestive of cholecystitis
LFTs - raised ALP is assoc w biliary pathology (bilirubin + ALT are usually normal - but bilirubin is increased in cholangitis)
Amylase - to check for pancreatitis (will be raised)
DIAGNOSTIC TEST TO CONFIRM GALLSTONES = Transabdominal USS (stones, gallbladder wall thickness, duct dilation)
Magnetic Resonance Cholangio-Pancreatography (MRCP) - produces detailed image of biliary system - used if USS shows no stones in duct but there is dilatation or raised bilirubin
Endoscopic Retrograde Cholangio-Pancreatography (ERCP) - an endoscope is inserted down the oesophagus, past the stomach, to the duodenum + opening of common bile duct. Main indication is to clear stones. Can inject contrast to visualise system.
CT scans are less useful - for DDx
If cholangitis may want to do blood cultures
How are biliary diseases treated?
Analgesia
IV fluids if dehydrated
Antibiotics if inflammation/infection (i.e. fever)
Cholecystectomy (gallbladder removal - gallstones are likely to reoccur if not) - indicated in symptomatic px or where there are complications. Usually laparoscopic
ERCP + stenting to mechanically clear blockage from bile duct
Treat any sepsis asap in cholangitis!
What is acute liver injury?
Acute: results in damage to + loss of cells
Causes
Viral A, B, EBV
Drugs - paracetamol poisoning
Vascular – ischaemia
Obstruction – usually bile
Congestion – from heart failure
What is chronic liver injury?
Chronic: eventually leads to fibrosis (when severe = cirrhosis)
Cirrhosis – disorganisation + fibrous scarring
Varices – due to portal hypertension
Hepatoma
Causes
Alcohol
Viral B, C
Autoimmune
Metabolic (excess iron - haemochromatosis, copper – Wilson’s)
How does acute liver injury present?
Malaise
Nausea
Anorexia
Jaundice
How does chronic liver injury present?
Ascites (fluid accumulation in the peritoneal cavity)
Oedema
Haematemesis (ruptured varices) – vomiting blood
Malaise
Anorexia
Wasting
Easy bruising (since liver produces clotting factors)
Itching
Erythema nodosum
Spider naevi
Hepatomegaly
Abnormal LFTs
Jaundice (rarer)
Confusion (rarer)
Asterixis - flapping tremor
Get varices due to portal hypertension - biggest cause is cirrhosis. When the liver is injured myofibroblasts contract which resists BF
Also get splenomegaly as it -> splenic vasodilation
What is liver disease?
Alcoholic liver disease
Fatty liver -> alcoholic hepatitis -> cirrhosis
Non-alcoholic fatty liver disease
Healthy -> steatosis -> steatohepatitis -> fibrosis -> cirrhosis
Will have the sx + signs mentioned earlier. May have none.
RUQ pain
Nausea
Vomiting
Diarrhoea
Hepatomegaly
Ascites
Jaundice
Spider naevei
Most common cause of chronic liver dis in western world
Men in 40-50s
- Alcohol related fatty liver Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks.
- Alcoholic hepatitis Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.
- Cirrhosis This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
Non alcholic fatty liver disease (NAFLD) forms part of the “metabolic syndrome” group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes. It is estimated that up to 30% of adults have NAFLD. It is characterised by fat deposited in liver cells. These fat deposits can interfered with the functioning of the liver cells. NAFLD does not cause problems initially, however it can progress to hepatitis and cirrhosis.
How is liver disease investigated?
Bloods
FBC - elevated MCV, LFTs show elevated ALT + AST. ALP elevated later on in the disease, clotting will show elevated PT, U&Es (GGT very raised in alcoholic)
USS- may show the earlier fatty changes, can also show cirrhosis. A fibroscan is a specialised USS for the liver measuring fibrosis + steatosis
Liver biopsy - will confirm dx
Also in Fatty
Enhanced Liver Fibrosis (ELF) blood test + NAFLD fibrosis score
Endoscopy - to assess for + treat oesophageal varices
CT + MRI - fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.
How is liver disease treated?
Alcoholic
Stop drinking permanently - detoxification regime.
Vitamins + nutrient supplementation
Steroids for short term outcomes
Complications of cirrhosis - portal hypertension, varices, ascites, hepatic encephalopathy
Liver transplant (must be obtained from alcohol 3 months prior to referral)
Fatty
Weight loss + exercise
Control diabetes, BP + cholesterol
Avoid alcohol
Wernicke-Korsakoff encephalopathy (presents with ataxia, confusion + nystagmus)
Fatty liver is reversible cirrhosis is not
Alcoholic hepatitis: • Nutrition must be maintained with enteral feeding + if necessary vitamin supplementation • Steroids show short-term benefit • Infections should be treated and/or prevented; anti-fungal prophylaxis should be used • Stop drinking alcohol for life
Alcoholic cirrhosis: • Reduce salt intake • Stop drinking for life • Avoid aspirin + NSAIDs • Liver transplantation
Delirium Tremens
Delirium tremens is a medical emergency associated with alcohol withdrawal with a mortality of 35% if left untreated. Alcohol stimulates GABA receptors in the brain. GABA receptors have a “relaxing” effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors) having a further inhibitory effect on the electrical activity of the brain.
Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol. When alcohol is removed from the system, GABA under-functions and glutamate over-functions causing an extreme excitability of the brain with excess adrenergic activity. This presents as:
Acute confusion
Severe agitation
Delusions and hallucinations
Tremor
Tachycardia
Hypertension
Hyperthermia
Ataxia (difficulties with coordinated movements)
Arrhythmias
Managing Alcohol Withdrawal
The CIWA-Ar (Clinical Institute Withdrawal Assessment – Alcohol revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.
Chlordiazepoxide (“Librium”) is a benzodiazepine used to combat the effects of alcohol withdrawal. Diazepam is a less commonly used alternative. It is given orally as a reducing regime titrated to the required dose based on the local alcohol withdrawal protocol (e.g. 10 – 40 mg every 1 – 4 hours). This is continued for 5-7 days.
Intravenous high-dose B vitamins (pabrinex). This should be followed by regular lower dose oral thiamine.
Wernicke-Korsakoff Syndrome (WKS)
Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency.
Features of Wernicke’s encephalopathy
Confusion
Oculomotor disturbances (disturbances of eye movements)
Ataxia (difficulties with coordinated movements)
Features of Korsakoffs syndrome
Memory impairment (retrograde and anterograde)
Behavioural changes
Wernicke’s encephalopathy is a medical emergency and has a high mortality rate if untreated. Korsakoffs syndrome is often irreversible and results in patients requiring full time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.
What are the complications of liver disease?
Alcohol withdrawal
tremor, sweating, headache, craving and anxiety -> hallucinations -> seizures
-> Delirium tremens - treat with benzodiazepines (or diazepam)
Wernike-Korsakoff syndrome - alcohol excess leads to thiamine (vitamin B1) deficiency - give THIAMINE
Wernikes encephalopathy (medical emergency with high mortality rate) becomes Korsakoffs syndrome (irreversible, need full time care)
Ataxia, confusion, nystagmus, memory impairment
Mallory-weiss tear
Acute/chronic pancreatitis
What is liver cirrhosis?
The end stage of all progressive liver diseases. Irreversible once fully developed
Loss of normal hepatic architecture with bridging fibrosis + nodular regeneration.
This affects the BF through liver -> increased resistance -> portal HTN.
GD Dx is liver biopsy
Has a classification score called Child-Pugh - Ascites, encephalopathy, (high) bilirubin, (low) albumin + (long) prothrombin given 1-3 + added up to give a score
