Session 6 Flashcards
Give a small overview of normal liver function
Storage - Glycogen, vitamins, iron, copper
Synthesis - glucose, protein, lipids + cholesterol, bile, coagulation factors, albumin.
Metabolism/detoxification - Ammonia, drugs, alcohol, carbohydrate/lipids
What are the general symptoms of liver disease?
Links to the function of the liver
Can have vague symptoms: ◦ Nausea/vomiting ◦ Fatigue ◦ Anorexia ◦ Abdominal pain
More specidic: Jaundice - bilirubin issue
Oedema/Ascites - albumin deficiency
Bleeding/Easy bruising - clotting factors deficiency
Confusion - ammonia build up
Name some possible causes of acute liver failure
Rapid onset, no previous liver disease
◦ Paracetamol overdose
◦ Other medications e.g. tetracycline, aspirin in children
◦ Acute viral infections e.g. EBV, CMV, Hep A/B
◦ Acute excessive alcohol intake
What is cirrhosis?
Cirrhosis is the ‘end result’ of a lot of conditions
Develops in response to any chronic liver injury
◦ Ongoing inflammation causes fibrosis
◦ Associated with hepatocyte necrosis
◦ Resulting architectural changes (nodules)
These changes occur over the course of years
Irreversible
The end result is:
◦ Impairment of liver function
◦ Distortion of architecture
Has bubbly looking appearance from normal tissue constricted by bands of fibrotic tissue. Liver can shrink from this fibrotic tissue.
What is alcoholic liver disease?
Damage to the liver that occurs after exposure to alcohol
Three main mechanisms by which alcohol can affect the liver:
◦ Fatty change (weeks) due to increased triglyceride production from alcohol metabolism – initially reversible
◦ Alcoholic Hepatitis (years) – initially reversible
◦ Cirrhosis (years) – end stage; irreversible damage
Thought to be partly due to build up of acetaldehyde
Identified by the history
May be asymptomatic, or have general symptoms of liver disease
Fatty liver:
◦ Hepatomegaly
Alcoholic hepatitis:
◦ Rapid onset jaundice, tender hepatomegaly (RUQ pain)
◦ Symptoms of more severe disease e.g. nausea, oedema and ascites, splenomegaly
Aim to reduce alcohol intake
How can infection cause cirrhosis?
Viral Hepatitis Chronic Hepatitis B or C
◦ Blood borne viruses
Potential for chronic infection
Also poses risk for hepatocellular carcinoma
Remember:
- Hep B has a vaccine but no cure - May have symptoms during acute infection
- Hep C has a cure but no vaccine - Majority are asymptomatic during acute infection
What is non-alcoholic fatty liver disease?
Accumulation of triglycerides and other lipids in hepatocytes.
Fat in the liver can lead to damage and inflammation resulting in cirrhosis. Also called Non-alcoholic steatohepatitis - NASH
Linked to insulin resistance.
Becoming more prevalent
Risk factors: ◦ Obesity ◦ Diabetes ◦ Metabolic syndrome (dyslipidaemia) ◦ Familial hyperlipidaemia
Treatment
Reduce risk factors/lifestyle modification
Oral hypoglycaemic agents
How can deposition of copper or iron cause cirrhosis?
Hereditary haemochromatosis
Abnormal iron metabolism
◦ Increased absorption of iron from the small intestine leading to excess deposition (liver stores iron) can affect other body systems e.g. pancreas which can also cause diabetes)
◦ Autosomal recessive
◦ Increased ferritin (beware ferritin is an acute phase response protein so doesn’t necessarily give definite diagnosis)
◦ Risk of developing hepatocellular carcinoma
Treatment is regular venesection so removing blood to lower iron.
Wilson’s disease
Abnormal copper metabolism, copper stored in liver.
◦ Reduced secretion of copper from biliary system -> accumulation in tissues
Can also affect other tissues particularly the brain
◦ Autosomal recessive
◦ Low caeruloplasmin - helps secrete copper.
Describe how autoimmune conditions can cause cirrhosis
Quite rare
Autoimmune hepatitis - autoimmune damage to hepatocytes - increases anti smooth muscle antibody and anti nuclear antibody
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) cause inflammation of the bile ducts. PBC is antimitochondrial antibody (AMA) positive and mainly affects women and PSC is AMA negative and mainly affects men
Name some other causes of cirrhosis unrelated to drugs, infection, deposition of substances or autoimmune conditions
Alpha 1 antitrypsin deficiency
Glycogen storage
Budd-Chiari
What is portal hypertension?
Build up of blood in the portal venous system
◦ Fibrotic liver is not very expansive
◦ Compresses veins entering the liver from the portal venous system
◦ This causes increased hydrostatic pressure in the portal venous system leading to ascites
◦ Also causes a build up of pressure in the splenic circulation leading to splenomegaly When this happens:
◦ Blood can ‘shunt’ from the portal system to the systemic venous circulation via connections (anastomoses) that are not usually used.
◦ This leads to distension of the veins at the site of anastomoses causing varices
Describe the three important sites of varices related to portal hypertension
- Oesophageal (most common)
◦ Upper 2/3 drains into oesophageal veins
◦ The distal portion drains to left gastric vein
◦ When there’s portal hypertension, pressure builds up pushing blood that would normal exit via the left gastric vein instead exits via oesophageal veins and so this can lead to mucosal varices.
◦ If these rupture it can cause significant haematemesis
- Anorectal
Normally blood leaves upper 1/3 of anal canal via superior rectal into inferior mesenteric but when there’s portal hypertension can leave via middle or inferior rectal into internal iliac which drains into the IVC
◦ Between superior and middle / inferior rectal veins
◦ Typically painless (above pectinate line)
◦ Rarely bleed
- Umbilical
◦ Not as common
◦ Ligamentum teres (obliteration of umbilical circulation coming in) links the liver to the umbilicus
◦ Normally no blood flow but connects to portal vein so blood can get backed up here
◦ Caput medusa (medusa like appearance of varices)
What is hepatorenal syndrome?
This is the development of acute Kidney Injury (AKI) in the presence of cirrhosis
Cirrhosis leads to portal hypertension which leads to arterial vasodilation (splanchnic) so RAAS is activated leading to renal artery vasoconstriction which reduces blood flow to the kidney causing AKI
Kidney function improves dramatically if the patient’s liver failure is reversed
What is the structure of the biliary tree?
Right and left hepatic ducts meet to from common hepatic duct which meets the cystic duct from the gall bladder to form the common bile duct which meets the pancreatic duct to form ampulla of vater which drains into the duodenum through the sphincter of oddi.
What are gallstones?
Formed from bile contents:
◦ Cholesterol (most common)
◦ Bile pigments
◦ Mixed Most are radiolucent - don’t show on X-ray.
◦ Comparison to renal calculi (kidney stones) which do show up on X-ray
Risk factors:
Diet and lifestyle
Age - 40s/50s most common
Gender - more common in women
Pregnancy
Pre-existing liver disease
What are the possible complications of gallstones?
Biliary colic
◦ RUQ pain ◦ Typically a few hours after eating a fatty meal (CCK)
◦ Temporary obstruction of a gallstone usually in the cystic duct
◦ Seen on US
◦ No features of inflammation
Management = analgesia, elective cholecystectomy
Acute cholecystitis
◦ Initial presentation very similar to biliary colic
◦ Permanent impaction of a stone in the cystic duct
◦ Inflammatory features
◦ Seen on US – thick wall gallbladder
◦ Murphy’s sign positive - when patient breathes the liver and gall bladder will go down so palpate under right side of ribs and as they breathe your hand will come into contact with the inflamed gall bladder and the patient will feel pain.
Management = initially conservative, then cholecystectomy
Acute (ascending) cholangitis
◦ Infection of the biliary tree
◦ Present with pain, features of inflammation, and jaundice - ‘Charcot’s triad’
◦ Typically due to an impacted common bile duct stone or other obstructive causes and then causes infection behind it.
Management = IV antibiotics, fluids, relieve obstruction
Acute pancreatitis
◦ Acinar cell injury and necrosis
◦ Blockage of pancreatic duct e.g. from gallstones
◦ Evokes an inflammatory response
◦ ‘Autodigestion’ of pancreas as proteases cannot get out of pancreas
Presentation: Epigastric pain ◦ Radiates to back ◦ Often associated with vomiting ◦ Cullen’s (bruising around the umbilical region) and Grey Turner’s (bruising down the flanks of abdomen) sign
Damage to pancreas can lead to release of amylase and lipases which can be measured.
What is Bilirubin? Describe its metabolism
Haemoglobin is broken down into haem and globin by splenic macrophages in the spleen (can also occur in liver but mainly spleen).
Bilirubin is the breakdown product of haem
Initially unconjugated so not water soluble so must bind to albumin.
Conjugated in the liver to become water soluble.
Several outcomes:
- Round and round through enterohepatic circulation
- Converted to urobilinogen in intestines and excreted in faeces as stercobilin (oxidised urobilinogen)
- Goes to kidney from liver as bilirubin (converted to urobilinogen in kidneys) or from intestines as urobilinogen to be excreted in urine as urobilinogen
Briefly summarise types of jaundice and their associated causes and presentations
