WEEK 5 - Hepatic Disorders Flashcards
What is the purpose of the hepatic portal system?
- Allows the liver to take out glucose for storage after meals
- Allows toxic molecules to be partially detoxified before blood moves on to the heart
What is hepatitis?
Inflammation of the liver characterised by:
Hepatomegaly Poor appetite Abdominal discomfort Abnormal liver function Jaundice Clay coloured stool Tea coloured urine
What are the causes of hepatitis?
Infection - viral, bacterial, parasitic
Alcohol
Drugs and toxins
Transfusion of incompatible blood
Characteristics of Hep A?
- RNA virus
- Transmitted via faecal-oral route (contaminated food/water)
- Asymptomatic infection in children
- High risk groups: travellers, men who have sex with men
Characteristics of Hep B?
- Transmitted parenterally, sexually and perinatally
- DNA virus
- Becomes chronic after six months
- The earlier the age of infection the greater the likelihood of carrying it for life
Characteristics of Hep C?
- RNA virus
- Effects intravenous drug users (spread parenterally)
- Becomes chronic after 6 months
- Can cause liver failure if left untreated
- Only 1 in 4 will recover
Characteristics of Hep D?
- RNA virus
- Can only occur in people with Hep B
- Can be prevented with Hep B vaccine as they share molecules of their viral coats
- Causes a more severe infection
- Spread parenterally, sexually and perinatally (same as Hep B)
Characteristics of Hep E?
- No vaccine, has many strains
- Linked to undercooked meat and seafood
- Spread via faecal-oral route
Characteristics of Hep G?
- Structurally similar to Hep C
- Little or no symptoms
- Spread parenterally, sexually and perinatally
What is the pathophysiology of hepatitis?
- Causes direct cellular injury: necrosis and scarring of hepatocytes, hyperplasia and infiltration by mononuclear phagocytes
- Leads to an immune response that damages and obstructs the bile ducts
What clinical manifestations occur in acute fulminating hepatitis?
Necrosis
Encephalopathy
Liver failure
Death
Clinical testing for hepatitis?
- Abnormal LFTs = raised AST (aspartate transaminase) and ALT (alanine transaminase)
- ALP = biliary system obstruction (lines the biliary duct)
- LFTs may be in normal range in chronic liver disease
Describe the four stages of hepatitis
- Incubation period - most infectious during this time
- Prodromal phase - early, non specific syndrome: fatigue, GI disturbances, weight loss, anorexia, headache, rash, fever, jaundice (last step)
- Icteric phase - jaundice, yellow skin, itching, tea coloured urine, clay coloured stool, fatigue, hepatomegaly
- Recovery phase - jaundice and other S&S subside, liver function returns to normal, full recovery in most people
Diagnosis of hepatitis?
Not based on symptoms alone as they are nonspecific
- Blood tests for virus-specific antibodies
- HBsAg - Hep B specific antigen
LFTs for liver function indication
Treatment for acute viral hepatitis?
- Restriction of physical activity
- Low fat and high carb diet
- Smaller, more frequent meals to spread out metabolism
- Hand washing and avoid contact with bodily fluids
(no real treatment)
Treatments for chronic hepatitis?
- HepB: treatments to slow progression
- HepC: curable with 95% success rate
What is hepatic encephalopathy?
- Neurological impairment secondary to hepatic dysfunction
- Characterised by neural disturbances due to increased ammonia levels
How does ammonia cause neural disturbances?
- Ammonia is a byproduct of protein metabolism
- Inability of the liver to detoxify ammonia = ammonia build up = reaches the brain via the BBB
- Ammonia is metabolised into glutamine - interferes with neurotransmitters, astrocyte oedema = brain herniation, oedema, death
Diagnosis of hepatic encephalopathy?
- Hx of liver disease in addition to:
- Signs and symptoms
- Blood tests (for high ammonia levels)
Treatment for hepatic encephalopathy?
- Fluid and electrolyte correction
- Restrict dietary protein
- Neomycin (eliminates bacteria for protein metabolism)
- Lactulose (promotes excretion of ammonia)
What is liver cirrhosis?
Occurs at the end of chronic liver disease
Irreversible inflammatory condition where liver tissue is replaced by dysfunctional fibrotic tissue
What are the different types of liver cirrhosis?
- Alcoholic cirrhosis
- Biliary cirrhosis
- Post-necrotic cirrhosis
- Metabolic cirrhosis
Pathophysiology of liver cirrhosis?
Poorly understood
- Fibrosis due to inflammation and necrosis
- Functional hepatocytes replaced by scarred nodules
- Leads to a hard, dysfunctional liver
- Obstruction to vascular network reduces the blood flow to the liver and may lead to portal hypertension
- Biliary duct obstruction leads to bile stasis and leakage of bile = necrosis of hepatocytes, jaundice and pain
Pathophysiology of alcoholic cirrhosis?
Metabolism of alcohol produces acetaldehyde = damages hepatocytes, causes inflammation
Pathophysiology of biliary cirrhosis?
Obstruction of biliary duct blocks bile flow = inflammation and scarring of hepatocytes
Primary - autoimmune condition
Secondary - physical obstruction (tumours, gallstones, pancreatitis)
Pathophysiology of post-necrotic cirrhosis?
Severe damage from viral hepatitis, drug toxicity or autoimmune disease - necrotic tissue is replaced with fibrous nodular scar tissue
Pathophysiology of metabolic cirrhosis?
Disorders associated with metabolic function eg. Wilson’s disease, heamochromatosis
Clinical manifestations of alcoholic cirrhosis?
- Anorexia
- Fatigue
- Nausea
- Infection
- Weight loss
- Hepatomegaly
- Pain in the right upper quadrant
Diagnostic tools for alcoholic cirrhosis?
Clinical hx
LFTs
Liver biopsy
Treatment for alcoholic cirrhosis
Cessation of alcohol
Rest
Correct diet
Management of complications
Clinical manifestations of biliary cirrhosis?
Jaundice
Itching
Abdominal pain
Fatigue
Diagnosis of biliary cirrhosis?
Serologic tests = increased bilirubin, ALP and lipids - issues with bile ducts
Liver biopsy
Cholangiography
Treatment of biliary cirrhosis?
- Corticosteroids and azathioprine = suppress immune response
- Resolve cause of obstruction
- Liver transplant
What is portal hypertension?
High blood pressure in the portal venous system, most commonly due to cirrhosis, hepatitis or left sided heart failure
What is normal blood pressure in the portal system and what does it increase to in portal hypertension?
Normal = 3mmHg
Portal HTN = >10 mmHg
What are the clinical manifestations of portal HTN?
- Increased pressure leads to collateral vessel development in the oesophagus, stomach
- Varices (distended veins) = melina and anaemia
- Splenomegaly
- Ascites
What is ascites?
Accumulation of fluid in the peritoneal cavity, also known as third spacing, due to sodium retention in the kidneys
What are the clinical manifestations of ascites?
- Abdominal distension and discomfort
- Dyspnoea
- Difficulty walking
Treatment for ascites?
- Dietary restriction of Na+
- K+ sparing diuretics
- Paracentesis to drain the peritoneal space
When does hepatic necrosis occur?
Final stages of liver disease, occurs when 80-90% of the liver has undergone necrosis, prolonged insult tot he liver
Causes of fulminant hepatic failure (acute)?
- Hep A, B, D and E
- Viruses in immunocompromised patients
- Paracetamol OD
- Liver ischaemia secondary to hepatic venous obstruction
- Cardiogenic shock or neoplasms
Causes of chronic hepatic failure?
- Alcohol abuse and cirrhosis
- Cytotoxic drugs (eg. methotrexate)
- Genetic metabolic diseases
Treatment of liver failure?
- Eliminating alcohol consumption
- Decreasing ammonia intake by controlling protein intake
- Preventing infection
- Transplant
Which of the hepatitis viruses are DNA and which are RNA?
DNA: Hep B
RNA: Hep A, C, D
?? unknown: Hep E, G
