Liver and Friends Flashcards
What are the 7 functions of the liver?
- Oestrogen regulation
- Detoxification
- Metabolism of carbohydrates
- Albumin production
- Clotting factor production
- Bilirubin regulation
- Immunity
What is alcoholic liver disease?
Liver damage caused by excess alcohol intake
Describe the epidemiology of alcoholic liver disease
- Most common cause of chronic liver disease in the western world
- Usually presents in men in 40s-50s
What are 2 causes of alcoholic liver disease?
- Excessive consumption of alcohol (main)
- Some genetic predisposition
Describe the order of alcoholic liver disease
Fatty liver (steatosis) –> alcoholic hepatitis –> cirrhosis
Describe the pathophysiology of fatty liver (steatosis)
- Metabolism of alcohol produces fat in the liver
- Cells become swollen with fat with large amounts of alcohol
- Fat disappears on alcohol abstinence
- Alcohol directly affects stellate cells (fat-storing cells) which are transformed into collagen-producing myofibroblast cells
Describe the pathophysiology of alcoholic hepatitis
- Fatty change and infiltration by polymorphonuclear leukocytes and hepatocyte necrosis
- Presence of mallory bodies and giant mitochondria
What are 4 signs of alcoholic liver disease?
- Hepatomegaly
- Ascites
- Rapid onset jaundice
- Encephalopathy
What are the symptoms of fatty liver (alcoholic liver disease)?
Usually asymptomatic
What are 4 symptoms of alcoholic hepatitis (alcoholic liver disease)?
- Nausea and vomiting
- Diarrhoea
- Anorexia
- RUQ pain
What is a symptom of alcoholic cirrhosis (alcoholic liver disease)?
May be asymptomatic
- Spider naevi (clusters of RBCs visible under skin)
What are 8 investigations for patients with alcoholic liver disease?
- LFTs
- FBC
- PTT (increased)
- Abdominal ultrasound
- Fibroscan
- Endoscopy
- CT/MRI
- Liver biopsy
Describe LFT results for patients with alcoholic liver disease
- GGT = very raised
- AST:ALT = raised ratio (2:1)
Describe FBC results for patients with alcoholic liver disease
- Macrocytic anaemia (elevated MCV)
- Thrombocytopenia
- Hypoglycaemia
What is the recommended alcohol consumption?
- No more than 14 units per week for both men and women
- No more than 5 units in a day
How do you calculate the number of units of alcohol?
Strength (ABV) x volume (ml) / 1,000
What is the treatment for alcoholic liver disease?
- Lifelong abstinence from alcohol
- Corticosteroids (to control inflammation)
- IV thiamine
- Diet high in vitamins and proteins
- Liver transplant
What are 5 complications of alcoholic liver disease?
- Liver failure
- Wernicke-Korsakoff encephalopathy
- Acute/chronic pancreatitis
- Mallory-Weiss tear
- Increased risk of cancers (particularly breast/mouth/throat)
What is non-alcoholic fatty liver disease?
Range of conditions caused by a build-up of fat in the liver
Describe the epidemiology of non-alcoholic fatty liver disease
25% of population
What are 3 risk factors for non-alcoholic fatty liver disease?
- Obesity
- Diabetes
- Hyperlipidaemia
Describe the order of non-alcoholic fatty liver disease
Healthy –> steatosis –> steatohepatitis –> fibrosis –> cirrhosis
What are 2 signs of non-alcoholic fatty liver disease?
- Hepatomegaly
- Jaundice
What are 5 symptoms of non-alcoholic fatty liver disease?
Asymptomatic
1. Nausea and vomiting
2. Diarrhoea
3. Fatigue
4. Malaise
5. RUQ pain
What are 4 investigations for patients with non-alcoholic fatty liver disease?
- LFTs (raised ALT and sometimes AST)
- CT/MRI
- Ultrasound
- Liver biopsy
What is the treatment for non-alcoholic fatty liver disease?
- Reduce weight
- No effective drug treatments
What is autoimmune hepatitis?
Liver inflammation due to the immune system attacking hepatocytes
Describe the epidemiology of autoimmune hepatitis
- Type 1 occurs in adults (typically women in 40s-50s around/after menopause)
- Type 2 occurs in children (typically teenagers/early 20s)
What are 4 signs and symptoms of autoimmune hepatitis?
- Hepatosplenomegaly
- Fatigue
- Fever
- Jaundice
What are 5 investigations for patients with type 1 autoimmune hepatitis?
- Biopsy
- Raised ALT and AST
- Anti-nuclear antibodies (ANA)
- Anti-smooth muscle antibodies (acin-acin)
- Anti-soluble liver antigen (anti-SLA/LP)
What are 4 investigations for patients with type 2 autoimmune hepatitis?
- Biopsy
- Raised ALT and AST
- Anti-liver kidney microsomes-1 (anti-LKM1)
- Anti-liver cytosol antigen type 1 (anti-LC1)
What is the treatment for autoimmune hepatitis?
- High dose steroids e.g. prednisolone, azathioprine
- Usually successful in inducing remission but is required life long
- Liver transplant (can recur)
What is viral hepatitis?
Inflammation of the liver as a result of direct viral infection
Describe the epidemiology of Hepatitis A
- Most common viral hepatitis worldwide
- Common in Africa and South America
How is Hepatitis A spread?
- Faecal oral route (facilitated by overcrowding and poor sanitation)
- Arises from ingestion of contaminated food/water e.g. shellfish
What are 3 risk factors for Hepatitis A?
- Shellfish
- Travellers
- Food handlers
Describe the pathophysiology of Hepatitis A
- Small, unenveloped RNA virus (picornavirus)
- Incubation period of 28 days
- Viral replication occurs in infected hepatocytes
- Hepatocytes destroyed due to immune response and viral life cycle
- = acute hepatitis
- Viral particles excreted in bile then faeces
What are 3 signs of Hepatitis A?
- Cholestasis
- Jaundice (after 2 weeks)
- Hepatomegaly (after 2 weeks)
What are 4 symptoms of Hepatitis A?
- Nausea and vomiting
- Anorexia
- Abdominal pain
- Dark urine and pale stool (after 2 weeks)
What are 2 investigations for patients with Hepatitis A?
- Raised ALT
- Antibody to HAV (IgM)
What is the treatment for Hepatitis A?
- Resolves without treatment in 1-3 months
- Treat symptoms = analgesia
- Avoid alcohol
- Vaccination
What are 2 complications of Hepatitis A?
- Cholestatic hepatitis
- Acute liver failure (rare)
How is Hepatitis B spread?
Direct contact with blood/bodily fluids (needles, sexual, IV drugs users, vertical transmission etc.)
What are 6 risk factors for Hepatitis B?
- Healthcare personnel
- Emergency/rescue teams
- CKD/dialysis patients
- Travellers
- Homosexual men
- IV drug users
Describe the pathophysiology of Hepatitis B
- Enveloped DNA virus
- HBsAg produced in excess by infected hepatocytes
- Virus penetrates into hepatocytes and loses its coat
- Virus core is transported to nucleus without processing
= acute and chronic hepatitis
What are 2 signs of Hepatitis B?
- Jaundice
- Hepatomegaly
What are 3 symptoms of Hepatitis B?
- Flu-like symptoms
- Fever
- Pruritus (itchy skin)
What are 3 investigations for patients with Hepatitis B?
- Blood = raised ALT
- Antibody tests:
- HBsAG (Hep B surface antigen)
- HBsAb (Hep B surface antibody)
What is the treatment for Hepatitis B?
- Most people fully recover from infection within 2 months
- Vaccination
- Stop smoking and drinking alcohol
- 10% go on to become chronic hepatitis B carriers
- Antiviral medication e.g. pegylated interferon-alpha 2a (48 week long treatment course)
What are chronic hepatitis B carriers?
Hepatitis B virus DNA has integrated into the host’s DNA so viral proteins continue to be produced
What are 2 complications of Hepatitis B?
- Cirrhosis and chronic infection –> hepatocellular carcinoma
- Fulminant hepatic failure (rare)
Describe the epidemiology of Hepatitis C
Six numbered genotypes = no.1 affects 50% of cases, no.2 and 3 make up 40%
How is Hepatitis C spread?
Via blood/bodily fluids (e.g. poorly sterilised instruments, shared needles etc.)
Describe the pathophysiology of Hepatitis C
- Enveloped RNA virus
- Incubation period of 6-9 weeks
- Chronic infection causes a slowly progressive fibrosis over years
What are 3 symptoms of Hepatitis C?
Often asymptomatic in acute phase but in chronic:
1. Malaise
2. Weakness
3. Anorexia
What are 2 investigations for patients with Hepatitis C?
- Hepatitis C antibody screening test
- Hepatitis C RNA testing
What is the treatment for Hepatitis C?
- 1/4 fight off and make full recovery
- 3/4 become chronic
- No vaccine available
- Stop smoking and drinking alcohol
- Curable with direct acting antiviral medications e.g. pegylated interferon-alpha 2a (8-12 week course)
What are 2 complications of Hepatitis C?
- Liver cirrhosis
- Hepatocellular carcinoma
How is Hepatitis D spread?
Blood-borne transmission (sexually, IVDU)
Describe the pathophysiology of Hepatitis D
- RNA virus
- Only occurs in people who are also infected with Hepatitis B
- Attaches to HBsAg to survive
What are 2 signs of Hepatitis D?
Signs of acute HBV infection:
1. Jaundice
2. Hepatomegaly
What are 3 symptoms of Hepatitis D?
Symptoms of acute HBV infection:
1. Flu-like symptoms
2. Fever
3. Pruritus
What is the treatment of Hepatitis D?
Same treatment as HBV:
- Stop smoking and drinking alcohol
- Antiviral medication e.g. pegylated interferon-alpha 2a (48 week long treatment course)
What is the complication of Hepatitis D?
Increases complications/disease severity of hepatitis B
Describe the epidemiology of Hepatitis E
Most common cause of acute hepatitis in the UK
How is Hepatitis E spread?
Faecal-oral transmission (raw/undercooked pork meat)
Describe the pathophysiology of Hepatitis E
- RNA virus
- Usually results in self-limiting acute hepatitis
What are the symptoms for Hepatitis E?
95% of cases are asymptomatic (usually self-limiting)
What is the investigation for patients with Hepatitis E?
Serology
What is the treatment for Hepatitis E?
- Often not required
- Treat symptoms
- No vaccine available
What is a complication of Hepatitis E?
Can progress to cirrhosis in immunocompromised (rare)
What is liver cirrhosis?
Scarring of the liver (fibrosis) caused by continuous, long-term liver damage - chronic inflammation and damage to hepatocytes
What are the 4 main causes of liver cirrhosis?
- Alcoholic liver disease
- Non-alcoholic fatty liver disease
- Hepatitis B
- Hepatitis C
What are 2 rarer causes of liver cirrhosis?
- Hereditary haemochromatosis (HH)
- Wilson’s disease (WD)
Describe the pathophysiology of liver cirrhosis
- Damaged hepatocytes are replaced with scar tissue (fibrosis)
- Fibrosis affects the structure and blood flow through the liver
- This increases resistance in the vessels leading into the liver (portal hypertension)
What are 4 signs of liver cirrhosis?
- Jaundice
- Hepatosplenomegaly
- Ascites
- Asterixis (inability to maintain sustained posture with subsequent brief, shock-like, involuntary movements)
What are 5 symptoms of liver cirrhosis?
- Spider naevi/caput medusae
- Palmar erythema
- Gynaecomastia
- Testicular atrophy
- Bruising
What are the 7 investigations for patients with liver cirrhosis?
- Bloods
- Imaging (CT/MRI/ultrasound/fibroscan)
- Endoscopy
- Liver biopsy
- Enhanced liver fibrosis blood test
- Child-Pugh score
- MELD score
What are the results of bloods in patients with liver cirrhosis?
- High AST:ALT ratio
- High bilirubin
- Decreased albumin
- Increased PTT/NR
- Thrombocytopenia
- Hyponatraemia
What is the enhanced liver fibrosis blood test?
< 7.7 = none to mild fibrosis
7.7-9.8 = moderate fibrosis
>9.8 = severe fibrosis
What does the child-pugh score calculate?
Indicates severity of cirrhosis
What does the MELD score calculate?
Gives a percentage estimated 3 month mortality
What is the treatment for liver cirrhosis?
- High protein, low sodium diet
- Fluids
- Analgesia
- Alcohol abstinence
- Liver transplant
What are 6 complications of liver cirrhosis?
- Malnutrition
- Portal hypertension, varices, variceal bleeding
- Ascites and spontaneous bacterial peritonitis
- Hepato-renal syndrome
- Hepatic encephalopathy
- Hepatocellular carcinoma
What is jaundice?
Yellow discolouration of sclera and skin due to hyperbilirubinaemia
What is the jaundice threshold?
Occurs at bilirubin levels roughly greater than 50 umol/L
What are 3 causes of pre-hepatic jaundice?
- Haemolytic anaemia (e.g. sickle cell, malaria)
- Gilbert’s syndrome
- Criggler-Najjar syndrome
What are 6 causes of intrahepatic jaundice?
- Alcoholic liver disease
- Viral/autoimmune hepatitis
- Iatrogenic
- Hereditary haemochromatosis
- Primary biliary cirrhosis/primary biliary cholangitis
- Hepatocellular carcinoma
What are 3 causes of posthepatic jaundice?
- Intra-luminal causes e.g. gallstones
- Mural causes e.g. cholangiocarcinoma, stricture, drug-induced cholestasis
- Extra-mural cases e.g. pancreatic cancer, abdominal masses (e.g. lymphoma)
What is bilirubin?
Breakdown product from catabolism of haem (formed from destruction of RBCs)
What usually happens to bilirubin?
- Conjugates with liver (becomes water soluble)
- Excreted via bile into GI tract
- Excreted in faeces as urobilinogen/stercobilin
- 10% of urobilinogen is reabsorbed into bloodstream and excreted via kidneys
Describe the pathophysiology of pre-hepatic jaundice
- Excessive breakdown of RBCs
- Liver overwhelmed to conjugate bilirubin
- = unconjugated hyperbilirubinaemia
- = unconjugated bilirubin in bloodstream
Describe the pathophysiology of intrahepatic jaundice
- Dysfunction of hepatic cells
- Liver loses ability to conjugate bilirubin
- Cirrhotic liver can cause obstruction
- = unconjugated and conjugated bilirubin in bloodstream
Describe the pathophysiology of post-hepatic jaundice
- Obstruction of biliary drainage
- Bilirubin is conjugated but cannot be excreted
- = conjugated bilirubin in bloodstream
Describe the clinical presentation/investigations of pre-hepatic jaundice
- Yellow sclera and skin
- Normal urine and stool
- No itching
- Normal LFTs
Describe the clinical presentation of intrahepatic jaundice
- Yellow sclera and skin
- Dark urine and pale stool
- Itching
- Abnormal LFTs
Describe the clinical presentation of post-hepatic jaundice
- Yellow sclera and skin
- Dark urine and pale stool
- Itching
- Abnormal LFTs
What are the 2 causes of Wernicke’s encephalopathy and Korsakoff syndrome?
- Alcohol excess
- Thiamine (vitamin B1) deficiency
Describe the pathophysiology of Wernicke’s encephalopathy and Korsakoff syndrome
- Thiamine is poorly absorbed in the presence of alcohol
- Thiamine deficiency causes damage to the hypothalamus and thalamus
- Further deficiency leads to damaged nerve cells and supporting cells in the CNS
- Wernicke’s = acute phase
- Korsakoff = chronic phase
What are 3 symptoms of Wernicke’s encephalopathy?
- Confusion
- Ataxia (difficulty with coordinated movements)
- Oculomotor disturbances
What are 3 symptoms of Wernicke’s encephalopathy?
- Confusion
- Ataxia (difficulty with coordinated movements)
- Oculomotor disturbances
What are 2 symptoms of Korsakoff’s syndrome?
- Memory impairment
- Behavioural changes
What is the treatment for Wernicke’s encephalopathy?
- Thiamine supplementation
- Abstaining from alcohol
What are complications of Wernicke’s encephalopathy and Korsakoff’s syndrome?
- Death if left untreated
- Korsakoff’s syndrome is irreversible and usually results in patients requiring full time institutional care
What is hepatic encephalopathy?
Changes in the brain that occur due to build up of toxins in the blood, particularly ammonia
What are 6 causes of hepatic encephalopathy?
- Constipation
- Electrolyte disturbance
- Infection
- GI bleed
- High protein diet
- Medications (particularly sedatives)
Describe the pathophysiology of hepatic encephalopathy
- Liver cirrhosis causes functional impairment of hepatocytes
- Hepatocytes cannot metabolise ammonia into harmless waste products
- Collateral circulation occurs in chronic liver disease (consequence of portal hypertension)
- Collateral vessels are made between portal and systemic circulation so ammonia can bypass liver
What are 2 symptoms of acute hepatic encephalopathy?
- Confusion
- Reduced consciousness
What are 3 symptoms of chronic hepatic encephalopathy?
- Personality changes
- Memory changes
- Mood changes
What is the treatment for hepatic encephalopathy?
- Laxatives (to clear ammonia from gut)
- Antibiotics (to reduce no. of bacteria in gut that produce ammonia)
- Nutritional support
Describe the epidemiology of pancreatic cancer
- 99% in exocrine component of pancreas
- More common in males >60
- Majority are adenocarcinomas
What are 7 risk factors for pancreatic cancer?
- Smoking
- Excessive alcohol/coffee intake
- Excessive use of aspirin
- Diabetes
- Chronic pancreatitis
- Family history
- Genetic mutations (presence of PRSS-1 mutation)
Describe the pathophysiology of pancreatic cancer
- Originates in ductal epithelium and evolves from pre-malignant lesions to full-invasive cancer
- 60% arise in pancreatic head
- 25% arise in body
- 15% arise in tail
- Tumour in head can grow large enough to compress the bile ducts and cause obstructive jaundice
- Tend to spread and metastasise early, particularly to liver, peritoneum, lungs and bones
What are 2 signs of pancreatic cancer?
- Acute pancreatitis
- Courvoisier’s law = palpable gallbladder and jaundice is usually caused by cholangiocarcinoma or pancreatic cancer
What are 3 symptoms of pancreatic cancer?
- Anorexia
- Weight loss
- Jaundice
What is a symptom of pancreatic cancer (body and tail)?
Epigastric pain that radiates to the back that is relieved by sitting forward
What are 3 symptoms of pancreatic cancer (head)?
Painless obstructive jaundice:
1. Yellow skin and sclera
2. Dark urine and pale stools
3. Generalised itching
What are 3 investigations for pancreatic cancer?
- Abdominal ultrasound/CT
- Biopsy
- Carbohydrate antigen 19-9 tumour marker = raised
What is the treatment for pancreatic cancer?
- Surgery
- Palliative therapy (often diagnosed late and has a very poor prognosis - 5% 3 year survival)
What are 4 surgeries for pancreatic cancer?
- Total pancreatectomy
- Distal pancreatectomy
- Radical pancreaticoduodenectomy (Whipple procedure)
- Pylorus-preserving pancreaticoduodenectomy (PPPD - modified Whipple procedure)
What are 5 palliative therapies for pancreatic cancer?
- Stents (to relieve biliary obstruction)
- Surgery to improve symptoms (e.g. bypassing biliary obstruction)
- Palliative chemotherapy
- Palliative radiotherapy
- End of life care
Describe the epidemiology of hepatocellular carcinoma
80% of primary liver cancers
What are 4 risk factors for hepatocellular carcinoma?
Liver cirrhosis due to:
1. Viral hepatitis B and C
2. Alcohol
3. Non alcoholic fatty liver disease
4. Other chronic liver disease
What are 2 signs of hepatocellular carcinoma?
- Hepatomegaly
- Ascites
What are 9 symptoms of hepatocellular carcinoma?
Often remains asymptomatic for a long time
1. Fever
2. Malaise
3. Weight loss
4. Abdominal pain
5. Anorexia
6. Nausea/vomiting
7. Jaundice
8. Pruritus
9. RUQ pain
What are 4 investigations for patients with hepatocellular carcinoma?
- CT/MRI liver
- Biopsy
- Alpha-fetoprotein (ATP) = raised
- Bloods = clotting abnormalities/deranged LFTs
What is the treatment for hepatocellular carcinoma?
- Poor prognosis
- Surgical resection
- Radiofrequency ablation
- Chemo/radiotherapy (palliative)
- TACE (transarterial chemoembolism - blocks blood supply to tumour)
- Kinase inhibitors (inhibits proliferation of cancer cells)
- Liver transplant
Describe the epidemiology of cholangiocarcinoma
- 20% of primary liver cancers
- Usually >50
- 90% = ductal adenocarcinomas
- 10% = squamous cell carcinomas
What are 2 risk factors for cholangiocarcinoma?
- Associated with primary sclerosing cholangitis (10%)
- Viral hepatitis B and C
What are 2 signs of cholangiocarcinoma?
- Hepatomegaly
- Ascites