List the functions of the hepatocyte with examples
Synthesis
- Albumin
- Lipoproteins
- Coagulation factors (2, 7, 9, 10)
- Glycogen
- Urea
- Bile salts
- Cholesterol
Excretion/Detoxification
- Bilirubin
- Bile salts
- Ammonia
- Alcohol
- Drugs
- Toxins
Storage
- CHO, lipids, iron, copper,
- vitamins A,D,E,K
Distinguish between acute and chronic liver disease
- ACUTE
- Onset days, weeks after exposure
- Resolve within 3 months (usually)
- CHRONIC
- Present for more than 6 months
- Lead to and are associated with cirrhosis (or irreversible scarring of the liver)
List some categories of liver syndromes
- Acute hepatitis
- Hepatobiliary disorders – cholestasis (impaired bile flow)
- Chronic liver disease/cirrhosis
- Without liver failure (compensated cirrhosis)
- With liver failure (hepatic decompensation)
- Hepatic malignancies (infiltration) - primary or secondary
- Isolated hyperbilirubinemias (not due to above)
List some acute liver diseases
- Viral hepatitis (HAV, HBV, HCV, HDV, HEV,
other –CMV, EBV) - Other infections: bacterial, parasitic
- Toxic - hepatic drug reactions
- Vascular disorders (eg. cardiac failure - ischaemia reperfusion injury)
- Fatty liver disorders - more often chronic
- Alcoholic liver disease - more often chronic
- Autoimmune hepatitis - more often chronic
- Other metabolic disorders, e.g., haemochromatosis, Wilson’s disease
List the features of acute hepatitis aka hepatocullular necrosis
Acute hepatitis (hepatocellular necrosis)
- Anorexia (profound), nausea, vomiting
- Lethargy
- Jaundice common
- Scleral icterus especially in people of colour
Acute hepatitis (hepatocellular necrosis)
- also:
- Dark urine: bilirubin-uria
- Tender (soft) liver
- Acute liver failure - not making clotting factors hence bruising/bleeding,
prolonged coagulation time (not corrected by vitamin K injection)
- Liver biochemistry: ALT >10 fold increased;
changes in BR, GGT, ALP less specific
Definec holestasis and describe the presenting symptoms
Cholestasis
- Impaired bile flow
- Jaundice common
- Dark urine: bilirubinuria
- Pale stools
- Malabsorption - long chain fatty acids,
fat-soluble vitamins (impaired coagulation)
- Pruritus
List the causes of biliary obstruction
There are many causes, the most common of which is due to mechanical obstruction of CBD
- gallstones: pain, fever, jaundice (triad)
- malignancy: pancreatic head, bile duct, other
- scarring: primary or secondary sclerosing cholangitis
- infection eg cholangitis, parasites
Some molecular (“medical”) causes
- Drug-induced cholestasis (eg amoxycillin/clavulanic acid)
- Cholestasis of pregnancy
- Primary biliary cholangitis (PBC, formerly known as PB cirrhosis)
List soem common causes of chronic liver disease
Common causes of CHRONIC liver disease
- Hepatitis viruses (B, C)
- Alcohol (NHMRC 2021 guidelines) vs 2009
- no more than 10 std drinks a week, no more than 4 in a day
- Metabolic disorders
- Non-alcoholic fatty liver disease (NAFLD, MAFLD), including non-alcoholic steatohepatitis (NASH, MASH) -> can progress to cirrhosis
- Iron storage disorder - haemochromatosis
List some rarer causes of chronic liver diseases
- Drugs and other toxins, e.g., methotrexate, arsenic
- Metabolic disorders
- Copper storage disorder - Wilson’s disease (children, young adults)
- Glycogen storage diseases (babies)
- Autoimmune diseases
- autoimmune hepatitis
- primary biliary cholangitis (PBC)
- primary sclerosing cholangitis
Describe the presentation of liver failure with portal hypertension
- Ascites
- Dilated abdominal wall veins
- Muscle wasting (check shoulders, buttocks, thighs)
- Fullness left flank (splenomegaly)
Describe ascites pathophysiology
- Cirrhosis
- Low albumin
- Low colloid oncotic pressure -
- High portal pressure
- Increased capillary hydrostatic pressure
- High aldosterone and ADH
- Na+, water retention
- Low albumin
Inevitably leading to
- Fluid transudation
- ascites
Describe the features of cirrhosis and deceompensated liver failure
- Jaundice
- Ascites
- Impaired protein synthesis, coagulopathy
- Catabolism: muscle wasting
Describe some of the features of hepatic encephalopathy
- mood or personality swings
- behaviour and impulse control issues
- problems with memory, concentration, thinking
- consciousness, lucidity, sleep pattern changes
- coordination and motor function issues
- loss of autonomy, ability to self-care
- issue of clearing ammonia
Describe the complications of cirrhosis
- Portal hypertension
- Portal hypertensive gastropathy (vascular ectasia - oozy lining of stomach, vessels markedly dilated)
- Oesophago-gastric varices (catastrophic upper gastrointestinal bleeding)
- Thrombocytopenia (TPO down)
- Ascites/ hepatic encephalopathy
- Bacterial infection – impaired immunity (reduced complement synthesis), especially spontaneous bacterial peritonitis, septicaemia, pneumonia
Metabolic Defects
- Hypoglycemia
- Gluconeogenesis, glucose intolerance, diabetes
- Impaired drug clearance (CYP-mediated metabolism, hepatic blood flow)
Circulatory Disorders
- renal failure - hepatorenal syndrome (renin-angiotensin-aldosterone, ADH activation)
- hepatopulmonary syndrome (NO–> hypoxia, clubbing, pulmonary hypertension)
Briefly describe HCC
- 2nd most common cause of cancer death worldwide
- Incidence trebled in Australia and USA last 3 decades
- Regard as a complication of cirrhosis (>90% of cases)
- Most common in chronic viral hepatitis (B, C, B+C)
- … and longstanding cirrhosis, especially males, HBV/HCV, alcohol, fatty liver (NASH)
- Cholangiocarcinoma – less common; different associations e.g., primary sclerosing cholangitis, schistosomiasis
Describe the clinical approach to someone with liver disease
- HISTORY
- Features of acute hepatitis, biliary tract disease, cholestasis, cirrhosis, etc
- Risk factors (viral hepatitis, alcohol, medication, family history, metabolic disease - changes in body mass/shape)
- PHYSICAL EXAMINATION
- Liver size, consistency; spleen
- Jaundice, features of chronic liver disease, liver failure
- LIVER BIOCHEMISTRY and other lab tests
List some clinical features of liver disease
- Anorexia
- Confusion - enceph
- Dark urine - bilirubin
- Scratch marks
- Liver tenderness
- Black stools - depends, eg yes if varices
- Peripheral stigmata: high sensitivity, spider naevi from SVC: nipple line to head
Briefly describe what to look for on LFT
- Patterns of pathophysiology – hepatocellular, cholestatic, mixed
- Degree of change: increased, decreased, fold change
- Very little about prognosis and liver function (albumin, bilirubin, PT), fibrotic progression (platelets)
- Nonspecific changes most common - many causes; some trivial, some critical
- Any persistent elevation in liver tests – INVESTIGATE!
List the liver enzymes*
- ALT – alanine aminotransferase (30 - 40 U/L)
- AST – aspartate aminotransferase (30- 40 U/L) (also in cardiac, skeletal muscle, brain, kidney)
- ALP – alkaline phosphatase (also in bone) (20 -110 U/L)
- GGT – gamma glutamyltransferase (< 45 U/L)
- Raised ALP in presence of raised GGT – suggestive ALP of liver origin
- BR (2 – 20 U/L)
- ULN: upper limit of normal
- Normal ranges: provided
List some causes of raised liver enzyme test results
Hepatocellular Pattern (ALT > 2X ULN)
- CAUSES – alcohol, drugs, viral hepatitis, fatty liver, haemochromatosis, autoimmune hepatitis
Cholestatic Pattern (ALP > 2X ULN)
- CAUSES – choledocholithiasis, drugs, malignancy, primary biliary cholangitis (PBC), primary sclerosing cholangitis
Mixed
- CAUSES - fatty liver, alcohol, drugs, viral hepatitis
Provide examples of pathology and results
- Hepatitis (Hepatic Necrosis, Necro-Inflammatory Change):
- ALT >2 -5 x ULN, GGT raised, ALP less raised
- Cholestasis:
- ALP >2x ULN, GGT raised, ALT less raised; bile acids raised; conjugated hyperbilirubinemia (often), prolonged prothrombin time/INR, corrected by vitamin K injection
- Cirrhosis (Chronic Liver Disease):
- (May be normal); low albumin, prolonged PT, low platelets
- Infiltration, Malignancy:
- Non-specific - elevated GGT, ALP, ALT
- Hyperbilirubinemia:
- Conjugated or unconjugated (Gilbert’s syndrome)
- (Isolated) Unconjugated hyperbilirubinemia
Describe Gilbert’s and Crigler-Najjar
Gilbert’s Syndrome
- Common: 3-7%
- Defect (extra TATA sequence) in promoter of bilirubin UDP-glucuronosyl transferase (BR-GT)
- Life-long, mild (BR rarely exceeds 50 µmol/L)
- Worse with fasting, stress
- No bilirubinuria; other LFTs normal
- No symptoms (minimal jaundice)
Crigler-Najjar Syndrome
- Very rare
- Babies/children
- Absent BR-GT
- BR often >500 µmol/L – need phototherapy, plasma exchange to avoid brain damage (kernicterus)
Describe lab results for cirrhosis
Liver Biochemistry
- BR normal or raised
- ALT, AST - normal or raised: AST to ALT ratio >1
- ALP, GGT - normal or raised
Tests of Liver Synthetic Function
- Serum albumin - normal or LOW
- Prolonged prothrombin time
- Low platelets (↓thrombopoeitin)
Other:
- Anaemia common (GI blood loss), renal function, electrolytes- hyponatraemia due to dilutional effect, hypoglycemia, raised blood ammonia
What else are LFTs used for?
Model for End Stage Liver Disease
- Scoring system used for liver transplant candidates (‘urgency’)
- Based on 3 routine lab tests: BR, PT, Cr
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Coeliac19
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Intra-abdominal sepsis28
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GERD27
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Liver disease32
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Alcohol22
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Haemochromatosis14
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IBS IBD18
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Gallstones23
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Acute pancreatitis and chronic*15
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Viral hepatitis19
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Hepatitis C16
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CRC20
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Cirrhosis, CLD complication, fatty liver disease29
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CONSEQUENCES OF OBESITY18
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Control of body weight6
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Surgery to cure obesity and diabetes5
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Nutrition in adults20
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Nutrition in infants21
