Liver Flashcards
Function of liver:
Carbohydrate metabolism Lipid metabolism Protein and amino acid metabolism Synthesis of plasma proteins Synthesis and secretion of bile Drug and poison detoxification Detoxification of amonia through urea cycle Clearance of damaged cells, proteins, hormones
Hepatic artery:
Brings oxygenated blood to liver
Hepatic portal vein :
Low in oxygen
Brings nutrients from gut, spleen, pancreas
The liver….
Filters blood coming from digestive tract before passing it to rest of body…
…transforms and degrades substances and either returns them to the blood or excretes them into the bile
How hepatocytes process compounds:
1) Uptake of substance from the blood across the basolateral membrane
2) Transport of substance within the hepatocyte
3) The substance may be modified by enzymes in the hepatocytes
4) The hepatocyte excretes the substance or its products into the bile across the apical membrane or back into the blood through the basolateral membrane
Liver disease:
Hepatitis – inflammation of the liver triggers cell death by necrosis or apoptosis
Caused by…
- infection = hepatitis A, B, C, D, E viruses
- drugs = alcohol/paracetamol
- inherited = haemochromatosis, Wilson’s disease
- autoimmune = type 1 diabetes, sjogren’s syndrome
- hypertension, disbetes, obesity caused fatty liver
Acute hepatitis:
Inflammatory process triggers cell death by necrosis or apoptosis
Most common cause is by viral infection (A, B, C, D or E)
Also caused by certain drugs or poisons e.g. ethanol
Chronic hepatitis:
Viral infection (B, C or D)
Primary autoimmune disorders
Therapeutic drug-induced
Genetic disease e.g. Wilson’s disease
Fulminant (dramatic and overall) hepatic failure:
Viral infection (A, B, D, yellow fever…)
Poisons and toxins e.g. death cap mushroom, ethanol, halothane, paracetamol
Ischaemia or hypoxia – vascular occlusion, circulatory failure, sepsis with shock
Glycolysis =
Breakdown of glucose to pyruvate or lactose
Gluconeogenesis =
Conversion of non glucose molecules to glucose
Glycogenesis =
Glycogen formation
Glycogenolysis =
Glycogen breakdown
After eating:
Blood glucose increases
Increase insulin
Leads to glycogenesis
Between meals:
Increase glucagon
Decrease insulin
Leads to glycogenolysis/gluconeogenesis
Glucose release into bloodstream
Cholesterol:
Important component of call membranes
Precursor for bile acids
Precursor for steroid hormones
Bile acids…
- are formed from cholesterol in the hepatocytes
- 90% of bile acids are recirculated by the enterohepatic circulation system
Bile functions:
- Bile provides the sole excretory route for many solutes not excreted by the kidneys
- Secreted bile salts and acids are required for normal lipid digestion
Jaundice:
Yellow skin and sclera
Result of build up of bilirubin in the blood
Caused by…
Increased destruction of red blood cells or haemolysis
Decrease in ability of hepatocytes to conjugate bilirubin to glucuronic acid
- defect in ability of hepatocyte to absorb bilirubin (Gilbert’s syndrome)
- inability to conjugate bilirubin because of a deficiency in glucuronyl transferase (Crigier-Najjar syndrome and neonatal hyperbilirubinaemia)
- problems in transferring bilirubin-glucuronate to the biliari canaliculi (Dubin-Johnson and Rotor’s syndromes)
Blockage of biliary ducts by gall stones or tumour
Anti HBV (hepatitis B virus) approaches…
1) Entry inhibitors – impair viral propagation
2) DNA inhibitors/DNA destruction
3) Silencing – stop HBV RNA from forming
4) HBV RNA interference – knock down production of HBV proteins
Cirrhosis:
Cirrhosis is an irreversible damage to normal liver structure where scar tissue replaces healthy cells
- hepatic injury
- fibrosis
- nodular regeneration
Cause… excess alcohol consumption or HBV/HCV
Liver with chronic injury:
High density matrix containing fibril forming collagens.
Proliferating vitamin A deficient lipocytes
Loss of microvilli and fenestrations
Cirrhosis increases vascular resistance in the liver
The increase in vascular resistance increases pressure and decreases blood flow through the hepatic portal vein. This results in formation of alternative return routes to the heart.
Effects of portal hypertension :
oesophageal varices (prone to bleeding) enlarged spleen dilated abdominal veins ascites (abdominal fluid retention) haemarrhoides bile acid deficiency with malabsorption of fat and fat-soluble vitamins hyperglycaemia
Effects of liver cell failure :
hypoglycaemia coma jaundice ascites tendency to bleed (decreased prothrombin) anaemia ankle oedema fetor hepaticus (breath smells like a freshly opened corpse!)
During a paracetamol overdose…
- major pathway is saturated
- increased proportion oxidized to NAPBQI and conjugated with glutathione
- glutathione reserves become exhausted
- build-up of the toxic non-conjugated NAPBQ = liver cell necrosis
