Liver Disease Flashcards
What is the CMO 2016 Alcohol Guidance?
- Don’t regularly drink more than 14 units per week
- Spread evenly over 3 or more days
- Heavy drinking sessions increases risks
- Have several drink-free days a week
- Drink slowly, with food and water
What groups are likely to be most affected by drinking?
Young adults, elderly, low body weight, other health problems, on medications/drugs
What is the superior part of the liver covered by?
Diaphragm, pleura and lung
What is the inferior partof the liver covered by?
Diaphragm and pleura
What is the percussion sound of the superior part of the liver?
Dullness
What is the percussion sound of the inferior part of the liver?
Flatness
What are the principle functions of the liver?
Cholesterol metabolism Drug metabolism Carbohydrate metabolism Fatty acid metabolism Ammonia metabolism Protein synthesis Bile formation
What are the functions of bile?
Cholesterol/phospholipid homeostasis Electrolyte balance Conjugated bilirubin excretion Functional bile acid circulation Drug excretion
After aiding in digestion, where are bile salts reabsorbed?
By specialised mucosa in the terminal ileum
How is hepatitis A virus transmitted?
Transmission via faecal-oral route
What does Hep A lead to?
Replicates in hepatocytes (RNA virus)
Hepatocyte necrosis
Lymphocyte infiltration
How is Hep A excreted?
Bile –> faeces
What are clinical symptoms of Hep A?
Jaundice, dark urine, pale stools, anorexia
What is chronic liver disease?
A permanent and usually progressive pathological change throughout the liver
What happens to the liver in chronic liver disease?
Lobular architecture deranged
- Fibrosis and nodular regeneration (cirrhosis)
repeated injury to liver
What are the 3 main causes of chronic liver disease?
- Alcohol
- Fatty Liver Disease
- Hepatitis C
What are the other causes of chronic liver disease (less common)?
- Hepatitis B
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Auto-immune liver disease
What are the morphological results of cirrhosis?
- Hepatocytes damaged and function poorly
- Sinusoidal/cannalicular pathways disturbed
- Disrupted intrahepatic biliary drainage
- Disturbed vascular perfusion
What are the clinical effects of cirrhosis?
Jaundice Ascites Encephalopathy Portal hypertension Splenomegaly Bleeding tendency Endocrine abnormalities Renal failure Hepatocellular carcinoma
What is biliary obstruction ‘obstructive jaundice’?
Obstruction of the extrahepatic biliary system
Decreased excretion of bile
What is biliary obstruction commonly due to?
Gallstones or pancreatic cancer
What are the clinical effects of biliary obstruction?
Jaundice Dark urine Pale stools Itching Pain Steatorrhoea Weight loss Vitamin deficiencies Disturbed lipid metabolism
What is fatty liver disease caused by?
Alcohol, drugs, diabetes, obesity
What is the metabolic syndrome?
Metabolic syndrome is a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes
What is the ‘deadly quartet’?
- Abdominal obesity
- Diabetes mellitus
- Dyslipidaemia
- Hypertension
How does the liver play a role in protein synthesis?
Important site of protein synthesis for all circulating proteins except antibodies
- Albumin
- Apolipoproteins
- Clotting factors
How does the liver play a role in protein degredation?
Urea synthesis
Transamination and oxidative deamination of amino acids produces ammonia, which is converted in the liver to urea for safe disposal
How does the liver play a role in carbohydrate metabolism and glucose homeostasis?
Synthesis of glycogen in liver (for storage) and its availability for breakdown to help maintain blood glucose levels.
Liver is main site of gluconeogenesis where glucose is synthesised from other metabolites and used to maintain blood glucose levels during fasting
How is the liver involved in lipid metabolism?
Lipoprotein production: VLDL, LDL, HDL
Fatty acids and cholesterol synthesised in the liver (important for energy and maintenance of cell membrane)
How is the liver involved in bile metabolism?
Bile (acids/salts) synthesised in the liver
Liver important in production of bilirubin (comes from breakdown of haem)
What are bile salts synthesised from?
From cholesterol
How is the liver involved in processing hormones, drugs and toxins?
Cytochrome P450 system (involved in reactions that detoxify drugs etc normally by increasing their solubility)
How is the liver involved in immunological function?
Kupffer cells (ensure bacteria and other antigens from GI tract are degraded before entering general circulation)
Pit cells (liver associated NK cells)
What are the major causes of liver disease?
- Viral hepatitis
What viral hepatitis’s can cause liver disease?
Hepatitis A, B, C, E
What is hepatitis?
An inflammatory condition of the liver. It’s commonly caused by a viral infection, but there are other possible causes of hepatitis. These include autoimmune hepatitis and hepatitis that occurs as a secondary result of medications, drugs, toxins, and alcohol
Describe hepatitis A?
Most common globally (where sanitation is poor as spread through faecal-oral route), but usually least serious
Describe hepatitis B?
Spread through sexual contact, IV drug use, vertical (birth –> remain chronically infected)
More acute illness, may become chronic (1-5%) which brings risks of liver cancer and cirrhosis (treatment usually uneffective)
Describe hepatitis C?
Normally asymptomatic and chronic (treatment usually effective)
Transmitted through blood and blood products (i.e. re-use of needles)
Describe hepatits E?
Commonest in UK, resolves in most patients (normally from undercooked meat or shellfish, faceal-oral route)
Normally resolves on its own
Who does hepatitis D affect?
Only those who have hep B as hep D virus needs presence of hep B to survive
What can chronic infections of the liver lead to?
Fibrosis and cirrhosis
What is jaundice?
Yellow tinge to the skin/eyes due to build up of bilirubin
Vaccines for which hepatitis’ are available?
Hep A and B
What are the symptoms of Hep A?
Nausea, anorexia, jaundice
What are the symptoms of Hep B?
Majority have no symptoms during early stages
More severe than hep A: fever, nausea, anorexia, jaundice, rashes, pain, swelling of joints (polyarthritis)
Treat the symptoms !
What are the symptoms of Hep C?
Normally asymptomatic –> often diagnosed only when patient presents with chronic liver disease
What does alcoholic liver disease cause?
Inflammation and fatty acid accumulation –> causes fibrosis and cirrhosis
How does alcohol affect the brain function?
Inhibits the reticular activating system (RAS)
What does the RAS regulate?
The cerebral cortex (front part of brain)
What is the effect of the alcohol inhibiting the RAS?
Diminish intellectual faculties and reduces inhibitory effect of cerebral cortex on other areas –> lack of integration between sensory and motor control (loss coordination, judgement, control over movement)
How does alcohol metabolism affect the liver?
Increase in fatty acid synthesis and decrease in fatty acid metabolism in the liver
Resulting in accumulation of triacylglycerols (triglycerides) in hepatocytes
Inflammation (alcoholic hepatitis)
What is non-alcoholic fatty liver disease (NAFLD)?
Accumulation of triacylglycerols in hepatocytes which is not related to alcohol
What are the risk factors for NAFLD?
Obesity, hypertension, insulin resistance and type 2 diabetes, hyperlipidaemia
What do the majority of people with NAFLD develop?
Fat accumulation can be associated with inflammation (non-alcoholic steatohepatitis, NASH) which may develop into fibrosis and cirrhosis
What are the symptoms of NAFLD?
Normally asymptomatic until complications of liver disease and cirrhosis present e.g. jaundice, ascites, bleeding, HCC
Micronodular cirrhosis cause?
Stellate cells synthesise additional collagen (effectively scar tissue)
What does the disturbance of normal liver during cirrhosis affect?
Normal liver bile and blood flow through liver –> cells become swollen with fat droplets (steatosis)
As liver becomes inflamed there is evidence of immune cell infiltration
What can be seen at cellular level in cirrhosis?
Fat droplets and mallory bodies (aggregates of denatured keratin proteins)
What inherited conditions may cause cirrhosis of liver?
Galactosaemia, glycogen storage disease, Wilson’s disease
How can bile duct damage lead to cirrhosis of liver?
Bile accumulates and damages liver tissue
How can immune mediated damage lead to cirrhosis?
1ary biliary cirrhosis (autoimmune diseases)
How can drugs, toxins or infections lead to cirrhosis?
Reactions to drugs, parasitic infections
Distinguish hepatitis from cirrhosis of liver?
Hepatitis –> inflammation, reversible
Cirrhosis –> scarring, largely irreversible
What is albumin?
Albumin is a protein made by your liver. Albumin helps keep fluid in your bloodstream so it doesn’t leak into other tissues. It is also carries various substances throughout your body, including hormones, vitamins, and enzymes
What can low levels of albumin indicate?
Liver damage as insufficient hepatocytes for synthesis of albumin
What are low levels of albumin associated with?
Oedema and ascites (fluid in the abdomen) leading to swollen abdomen
Where is bilirubin conjugated? What is it conjugated with?
In the liver - conjugated with glucuronic acid (making it soluble in water) and it is released into bile duct
How can liver damage lead to a build up of bilirubin?
Lack of conjugation reaction due to damage to liver cells or blockage of bile duct due to extrinsic compression can lead to build up of bilirubin in plasma –> jaundice
How do increased levels of alkaline phosphatase indicate liver damage?
Released from damaged bile duct
How do increased enzyme levels in the plasma indicate damage?
Release of enzymes into plasma results from cell damage not increased synthesis
How do increased alanine transaminase and aspartate transaminase levels indicate liver damage?
Indicate liver damage as enzymes are released into plasma from damaged hepatocytes
What is the AST/ALT ratio?
The ratio between the concentrations of the enzymes aspartate transaminase (AST) and alanine transaminase (ALT)
o Ratio used as indicator of ongoing liver damage not degree of liver damage
What does an increased AST/ALT ratio suggest?
o Increased ratio suggests increasing degrees of fibrosis and indicates alcoholic liver disease
What do elevated y-glutamyl transferase levels imply?
Induced by alcohol and is an early indicator of liver dysfunction
What are other liver tests?
- Biopsy
- Ultrasound
What are key symptoms of liver disease?
- Jaundice
- Ascites
- Oesophageal varices
- Itchy skin
- Steatorrhea
- Easy bruising or bleeding
- Hypoglycaemia
What is ascites?
Fluid retention in the abdomen
What is oesophageal varices?
Caused by portal hypertension and leads to vomiting blood
Fibrosis in the liver disrupts the flow from the portal vein through the liver as there is increased resistance
- Route of least resistance is found –> communications between portal venous system and systemic circulation open up e.g. veins in lower oesophagus and upper stomach (varices) which can start to bleed
How can liver disease lead to itchy skin?
Build up of bile salts in the skin
How can liver disease lead to steatorrhea?
Due to pancreatitis –> lack of lipase secreted means fats can’t be broken down (fat in faeces)
How can liver disease lead to easy bruising or bleeding?
- Decrease in synthesis of clotting factors by liver
- Poor absorption of vitamin K (vital for creating full active clotting proteins)
- Platelet counts reduced
How can liver disease lead to hypoglycaemia?
Glycogenolysis (breakdown of liver glycogen) and gluconeogenesis don’t work well as liver is damaged so fewer hepatocytes to store glycogen or undertake gluconeogenesis
How does the metabolism of alcohol affect gluconeogenesis?
Breakdown of ethanol produces large amounts of NADH –> this inhibits entry of precursors such as pyruvate and lactate into gluconeogenesis –> gluconeogenesis is inhibited by alcohol breakdown which makes heavy drinkers hypoglycaemia (why alcohol makes you hungry)
What are heavy drinkers given if brought into hospital?
Glucose and thiamine (B1)
Why are heavy drinkers given thiamine (B1) injection?
Have a thiamine deficiency
Why do heavy drinkers have a thiamine deficiency?
o Deficiency due to poor diet (chaotic lifestyle, alcohol prioritised, malnourished)
o Damage to GI tract by alcohol reduces thiamine absorption
What is thiamine needed for?
- Needed to metabolise glucose
- Required as cofactor for pyruvate dehydrogenase catalyses ‘link’ reaction for entry of pyruvate into Krebs cycle:
Pyruvate + Coenzyme A + NAD+ Acetyl CoA + CO2 + NADH + H+
If the ‘link’ reaction is inhibited due to lack of thiamine, what happens?
If this reaction is inhibited, pyruvate is converted to lactate, leading to lactic acidosis
What is consequence of lactic acidosis?
Consequence is neurological damage (confusion, ataxia, coma) known as Wernicke-Korsakoff Syndrome (WKS)
Why can you not drink with certain drugs?
Competition between alcohol and many other drugs for cytochrome P450 enzymes causes slower clearance of both drugs and alcohol if taken together which increases risk of side effects and effect of alcohol
What drugs can you not drink. with?
Antidepressants, NSAIDs, antibiotics, benzodiazepines, antihistamines
What are problems when prescribing drugs to heavy drinkers?
o Chronic alcohol usage induces synthesis of CYP450 enzymes – leading to increased metabolism of prescribed drugs
o Increased dosage may be needed to obtain therapeutic effects
