Hepatic system disease Flashcards
What are some functions of the liver? [8]
1) Xenobiotic detoxification and metabolism
2) Decomposition of erythrocytes and excretion of bilirubin
3) Bile production
4) Cholesterol synthesis
5) Carbohydrate Metabolism
6) Protein synthesis
7) Hormone production
8) Storage
What is jaundice?
An elevation of serum biirubin above the normal limit (9mmol/L) 35 mmol/L
How is bilirubin metabolised in circulation?
Erythrocytes are broken down which releases haemoglobin
What happens to haemoglobin after breaking down?
The globin is metabolised and amino acids are recycled
The haem is converted to bilirubin, bound to albumin
How is bilirubin metabolised in the liver?
Dissociates from albumin and enters hepatocytes
What two components is bilirubin conjugated with?
Two glucouronic acids
Which enzyme causes the conjugation?
UDP-glucuronyl transferase
What property of bilirubin allows it to be secreted into the biliary canaliculi and bile?
It is water-soluble
What can bilirubin be digested into?
Urobilinogen
How is neonatal jaundice caused?
Bilirubin accumulates due to low glucuronyl transferase
What happens to unconjugated bilirubin in blood of babies?
It increases which causes diffusion into basal ganglia causing toxic encephalopathy
How do you treat jaundice in babies?
Expose the baby to blue fluorescent light as it converts bilirubin to a water-soluble isomer hence they can be excreted into bile without conjucation to glucoronic acid
What is Haemolytic Jaundice?
XS RBC lysis where bilirbuin if produced faster than the rate of conjugation by the liver
What happens to the blood, urine and stool during haemolytic jaundice?
Increase in unconjugated bilirubin in the blood
In urine the urobilinogen is increased
Stool is normal
What is Hepatocellular Jaundice?
Conjugated bilirubin is not efficiently secreted into bile.
What happens to the blood, urine and stool during haemolytic jaundice?
Blood- increased BOTH unconjugated and conjugated bilirubin
ALT & AST levels are markedly elevated
Urine-Bilirubin is present in urine, yellow brownish
Stool- Normal to Pale
What is obstructive jaundice?
Bile duct obstruction wherein conjugated bilirubin is prevented from passing to intestine; passed to blood increasing circulatory conjugated bilirubin
What happens to the blood, urine and stool during obstructive jaundice?
Blood: increased conjugated bilirubin ALT is mildly elevated
Urine: Bilirubin in urine, urobilinogen reduced
Stool: Pale (low stercobilin)
What is hepatitis?
Inflammation of the Liver
What is acute hepatitis?
Inflammation develops quickly and lasts short
What are examples of viral hepatitis?
Hepatits A
Hepatitis B
Hepatitis C
Hepatitis E
Give some information on Hepatitis A?
RNA Virus
Short incubation period
No chronic state
No carrier state
What is Hepatitis E?
Acute, self-limited, more severe liver damage, it is not lifelong, no treatment
What is Hepatitis B?
DNA Virus Spread by blood products, sexually Long incubation Carriers Fever malaise,anorexia, nausea 5-10%
What is the treatment for Hepatitis B?
Interferon alpha-2a recommended for initial treatment of adults with chronic hep B.
antivirals
5-10%
What is Hepatitis C?
RNA Virus
Blood, sexually
What is the treatment for Hepatitis C?
Sofosbuvir, uridine nucleotide analogue inhibits HCV polymerase, preventing viral replication
anti retrovirals
85% chronic
What is autoimmune hepatitis?
Autoantibodies against hepatocytes
What are the presentations of autoimmune disease?
Jaundice
RUQ Pain
May be associated with other autoimmune conditions
How do you treat autoimmune hepatitis?
Immunosuppressants (steroid, azathioprine)
What is cirrhosis?
Hepatocytes replaced by non-functional tissue
Hepatic failure
Portal vein hypertension adn shunting of blood aroun dliver
What are some causes of cirrhosis?
Alcohol Drugs and Xenobiotics Chronic Viral Hepatitis Autoimmune Hepatits Chronic Bile duct blockage Wilson's disease
What are some signs and symptoms od cirrhosis?
oedema - portal hypertension Gallstones Coagulation defects Peripheral neurpathy REduced Mental function Oesophageal and Gastric Varices and bleeding Jaundice
Treatment for cirrhosis?
Treat oedema with salt restriction and diuretic
Treat the chronic hepatic encephalopathy with laxatives and oral antibacterials
Treat the variceal haemorrhage with platelet transfusion
How does pathogenesis of alcoholic liver disease take place?
XS NADH via alcohol dehydrogenase therefore increased lipids
What is hepatic steatosis?
Lipid droplets accumulate in hepatocytes
What happens during alcohol-induced hepatocellular damage?
Induction of P450
Free radicals
adduct formation
What happens during alcohol-mediated hepatitis?
Swelling of hepatocytes
Mallory bodies (eosinophillic cytoplasmic inclusions)
Neutrophillic reaction
Fibrosis
What happens during alcohol-mediated cirrhosis?
liver becomes brown shrunked and non-fatty
entrapped hepatocytes
What are the clinical features of alcoholic liver disease?
Hepatic Steatosis
Alcoholic hepatitis
Alcoholic cirrhosis
What are the 3 hepatocyte zones?
1) Centrilobular (lowest O2)
2) Periportal (highest O2)
3) Midzone
What are the factors associated with DILI?
Inherent drug toxicity
Dose
Drug metabolites
Genetic polymorphism
DILI?
Drug Induced Liver injury
Mechanism of DIALD HAlothane Hepatitis
Look up youtube video
What is mitochondrial toxicity presesntation?
affects aerobically active tissues LOOk up
Drug biotransformation and elimination is a liver function
Drug elimination may be reduced in patients with significant liver dysfunction - thus blood levels may be higher for longer (toxicity vs effectiveness
Low clearance drugs
Often relatively little effect until end stage liver failure/cirrhosis as drug metabolism is relatively well preserved
High clearance drugs
Affected by portosystemic shunts - markedly increased systemic bioavailability of oral drugs
• Drug levels in blood may get very high
