Introduction to the Liver Flashcards
Describe distinguishable features of the liver
- Largest gland (2nd largest organ)
- Numerous functions; impacts all body systems
What is the significance of the livers structure?
Major aspects of it’s structure influence it’s functions:
- vascular system
- billiary tree
3D arrangement of liver cells with vascular and biliary systems
Describe the structure of the liver
Divided into 2 lobes by the falciform ligament
- each lobe has own blood supply
What is the role of the gallbladder?
Stores bile (is green sac)
How does bile reach the duodenum?
The common bile duct delivers bile into the duodenum
Describe the venous blood supply of the liver
majority (75%) of liver blood supply is venous blood from the portal vein, carrying blood returning from GI full of digested products
Describe the arterial blood supply to the liver
25% from the hepatic artery
Describe the venous blood flow in the liver
Blood from the central veins in the liver lobules drain into the hepatic vein and then into vena cava
What are the 2 primary cells of the liver?
Hepatocytes (60%) Kupffer cells (30%)
What is the function of hepatocytes?
perform most metabolic functions
What is the role of the endothelial kupffer cells?
(type of macrophage)
carry out phagocytic activity by removing aged / damaged rbcs, bacteria, viruses and immune complexes
How does the liver deal with toxic substances?
Hepatocytes remove toxic substances, including alcohol from the blood
exits lobule through central vein (hepatic venule)
Describe the counter-current flow of blood and bile
Blood flows in the opposite direction to bile
What is the functional unit of the liver?
Hepatic lobules
What are hepatic lobules?
Hexagonal plates of hepatocytes around a central hepatic vein
At each 6 corners there’s a triad of portal vein, hepatic artery and bile duct branches
Describe the flow of bile through the billiary system
Bile secreted by hepatocytes ↓ series of channels between cells (canaliculi) ↓ small ducts ↓ large ducts ↓ anastomose onto common bile duct
What is the benefit of the liver’s micro-structures?
Provides large SA for the exchange of molecules
How does the liver remove toxins?
Blood enters lobules through branches of the portal vein and hepatic artery, into smaller channels (sinusoid) lined with hepatocytes which pick up any bacteria from the intestine
What is bile?
Greenish-yellow liquid consisting of complex mix of water, electrolytes and organic molecules:
- bile acids
- cholesterol
- bilirubin
- phospholipids
What is the role of bile?
Essential for fat digestion & absorption via emulsification
Bile + pancreatic juice neutralises gastric juice as it enters the small intestine aids digestive enzymes
Elimination of waste products from blood in particular bilirubin & cholesterol
500mg of cholesterol converted to bile acids per day
What are the 2 stages of bile secretion?
- By hepatocytes:
- Bile salts, cholesterol & other organic constituents
- By Epithelial cells lining bile ducts
- Large quantity of watery Na+ & HCO₃⁻ solution
What causes the secretion of bile?
Release stimulated by secretin hormone in response to acid in the duodenum
Describe in detail the flow of bile
- Initially hepatocytes secrete bile into canaliculi
- Flows into bile ducts containing lots of bile salts,
cholesterol and other organic constituents. - Modified by water and bicarbonate-rich secretion from
epithelial ductal cells
How does the gallbladder end up storing bile?
Bile from hepatic ducts ↓ common bile duct ↓ duodenum OR diverted via cystic duct ↓ GALL BLADDER ↓ concentrated & stored (30-50ml) ↓ Released by CCK in response to fat in the duodenum
What is the role of the sphincter of Oddi?
controls entry of bile into duodenum
What is bilirubin?
Yellow pigment formed from breakdown of haemoglobin
Useless & toxic but made in large quantities
(~6g/day) → must be eliminated
What is the average lifespan of RBCs?
120 days
What happens to dead / damaged RBCs?
Digested by macrophages throughout body:
- Spleen
- Liver
- Red bone marrow etc.
What is the fate of the Fe from breakdown of RBCs?
Fe is recycled and stored in liver
What happens to the globin chains after RBC breakdown
Globin chains are protein → catabolized into amino acids for protein synthesis
What is the fate of haeme groups after RBC breakdown?
Haeme (porphyrin) cannot be recycled → eliminated
Explain how haeme is eliminated
Haem → bilverdin → bilirubin → liver → incorporated into bile
Outline how bilirubin is eliminated
- Haeme converted into free bilirubin, (intermediate
product is biliverdin) - Released into plasma; carried around body to liver
bound to albumin - Free bilirubin absorbed by hepatocytes → conjugated
with glucoronic acid (to become soluble in bile) - Conjugated bilirubin secreted into bile → metabolised
by bacteria intestinal lumen & eliminated into faeces /
urine
What pigments cause the colour of urine and faeces?
Major metabolite in faeces is Stercobilin – brown colour
In urine – Yellow urobilin & urobilinogen
What is jaundice?
Excessive quantities of free or conjugated bilirubin accumulated in ECF causing a yellow discoloration of skin, sclera and mucous membranes
What is the normal bilirubin content in the plasma?
Normal plasma [bilirubin] <17µmol/L (1.0 mg/dl),
How much bilirubin is required to cause discolouration?
discolouration > 34-51µmol/L (2-3mg/dl)
What is the sclera?
opaque, white outer layer of the eye
What are the 3 types of jaundice that can occur?
Pre-hepatic (haemolytic)
Hepatic
Post-hepatic (obstructive)
Explain the cause of Pre-hepatic (haemolytic) jaundice
Excessive RBC breakdown
Excess conjugated bilirubin not excreted - remains in circulation
Give an example of pre-hepatic jaundice
e.g. Neonatal jaundice
- baby in anaerobic environment in womb so lungs filled
with fluid
- switch to air when born →lots of RBCs broken down
Treatment: Light therapy (UV)
converts bilirubin→water soluble compound
Describe hepatic jaundice and its causes
Extensive (>80%) hepatocyte damage caused by:
- cirrhosis
- drugs
- Hepatitis A, B, C, E
- Gilbert’s syndrome
- excess (un)conjugated bilirubin
Give an example of hepatic jaundice
e.g. Gilbert’s Syndrome
- congenital disorder; patients have decreased enzyme to
conjugate bilirubin with glucoronic acid
- increases unconjugated bilirubin
What is post-hepatic (obstructive) Jaundice?
Excess conjugated bilirubin - enters circulation + urine
(v. dark urine)
Obstruction of passage into duodenum
What causes post-hepatic (obstructive) jaundice?
gallstones
carcinoma
pancreas/bile ducts
Which toxic substances does the liver metabolise?
Bilirubin Ammonia Hormones - e.g. inactivates all steroids: (androgens, oestrogen, cortisol, thyroxine, aldosterone) Drugs + exogenous toxins - e.g. aspirin, paracetamol, ethanol
What are the 2 phases the liver metabolises drugs and hormones in?
Phase 1 - oxidation/reduction
Phase 2 - Conjugation
*not all drugs require both phases
Explain what occurs in Phase 1 of metabolism
Primarily oxidation / reduction
Occurs in SER
Catalysed mainly by Cytochrome P450 family
=> polar compound formed
What happens in stage 2 of liver metabolism?
Conjugation to form a water soluble product
Glucoronyl is most prevalent
How are metabolised drugs / hormones excreted?
Elimination occurs via ATPase pumps
What is the chemical name of paracetamol?
acetaminophen
Why is overdose common with paracetamol?
Has a narrow therapeutic index so deliberate/accidental overdose is common
What is the maximum dose of paracetamol to be taken?
4 g/day or 1 g/dose
*not to be taken after alcohol consumption
How does the detoxification of paracetamol occur?
Metabolised by 3 pathways:
- Glucoronidation
- Sulfation (20-30%)
- N-hydroxylation and dehydration
- Intermediate = NAPQI (toxic)
- detoxified by GSH conjugation
What is the effect of Paracetamol overdose?
Liver enzymes become saturated
GSH stores are depleted
=> NAPQI builds up
Causes liver necrosis and kidney damage
How is paracetamol overdose treated?
Via infusion of N-acetyl cysteine (GSH precursor) to conjugate NAPQI
What are the 2 effects (phases) of Paracetamol overdose?
- damage not immediate
- effective treatment but given too late
Where in the body is alcohol removed from?
Only in the liver
What happens to alcohol consumed?
Alcohol →acetaldehyde (via alcohol dehydrogenase)
=> produces NADH used by pyruvic acid→lactate
=> lactate build up = acidosis
How does alcohol consumption lead to hypoglycemia?
pyruvic acid is a substrate for gluconeogenesis
=> can develop hypoglycemia after drinking
- reducing BGL
What is the fate of the NADH produced from alcohol metabolism?
NADH enters fat metabolism to generate FA and glycerol
→FA burnt off as energy→acetyl coA (driven by NADH)
→acetyl CoA→ketone bodies rather than entering tca
What happens if FA can’t enter the tca?
build up as ketone bodies
form excess lipids and are deposited in adipose tissue
What is the fate of acetaldehyde production from alcohol metabolism?
Acetaldehyde is toxic - needs removal:
Acetaldehyde→Acetate→circulation
via acetaldehyde dehydrogenase
Explain why alcohol flush reaction occurs so commonly among asians?
50% of asians have ALDH2 deficiency due to mutation of copy 1 gene → accumulation of acetaldehyde → alcohol flush reaction
What are the stages of alcohol induced liver damage?
Fatty liver → Liver fibrosis → cirrhosis
Describe a fatty liver caused by alcohol
Deposits of fat causes liver enlargement
Strict abstinence can lead to a full recovery
Describe liver fibrosis
Scar tissue forms on liver
Recovery is possible, but scar tissue remains
Describe liver cirrhosis
Growth of connective tissue destroys liver cells
Damage is irreversible
What are the effects of impaired detoxification?
Gynecomastia due to alcoholic cirrhosis
Name blood clotting factors synthesised in the liver
Fibrinogen
Prothrombin
nearly all other factors e.g. V, VI, IX, X, XII
What is the significance of vitamin K in coagulation factor synthesis?
Vitamin K is essential for prothrombin formation and Factors II, IX VII and X
What effect does liver damage have on clotting factors?
In severe liver disease, excessive bleeding may result due to a lack of coagulation factors
Outline the storage that occurs in the liver
Hepatocytes - depots for fat soluble vitamins: K, D, E A
Stores Vit. B12 , folate and Iron as ferritin
What is the consequence of liver dysfunction?
fat malabsorption→vit. deficiency
What is the effect of Vit. B12 deficiency?
pernicucus anemia
What is the requirement of folate?
Required during pregnancy
