The liver Flashcards
Describe the blood supply to the liver
- Double blood supply
- Hepatic artery (rich in oxygen, 30% of hepatic blood)
- Portal vein (from gut, 70% hepatic blood, rich in nutrients, poor in oxygen)
Where does the portal vein come from?
- Intestine
- Pancreas
- Spleen
Describe the venous drainage of the liver
- Vessels merge to form hepatic veins
- These merge to cauda vena cave to go back to heart
Name the lobes of the liver
- Quadrate in the middle
- Left and right each divided into lateral and medial
- Caudate (very caudal)
Describe the histological layers of the liver
- M esothelium on the outside (peritoneum) (single layer of cells)
- Then hepatic (Glisson’s capsule)
- Then hepatocytes
- Hepatic stroma made up of thin fibres of connective tissue
Describe the portal triad in the liver
- Made up of hepatic artery, portal vein and bile duct
- Surrounded by connective tissue
- If very large may also contain lymphatic vessels and autonomic nerves
What are hepatic sinusoids?
- Fenestrated blood vessels running along the plates of hepatocytes
- Portal and hepatic arterial blood mix in the sinusoids
What are the central veins?
- Found at the centre of classic hepatic lobule
- Receive blood from siusoids, return to circulation via hepatic vein
What cells make up the walls of bile ducts?
Simple cuboidal epithelium
What cells make up the walls of the blood vessels?
- Flat endothelial
- Thinner endothelium is vein, thicker is artery
Describe the arrangement of the hepatocytes
- Arranged into plates
- Have junctions
- Plates arrange to form the sinusoids
What is the limiting plate?
The discontinuous border of hepatocytes that forms the outer boundary of the portal tract
Describe the classical hepatic lobule
- Hexagonal shape
- Lines between portal triads with central vein in the centre
Describe the portal lobule
- Portal triad in the centre
- Triangular shape
- Points at central veins
Describe the hepatic acinus
- Oval shape
- Each end is central vein
- Sides at portal triads
- Can be divided into zones 1, 2 and 3
Compare the flow of the blood and bile in the liver
- Blood flows out of vessels and into sinusoids
- Bile being produced by hepatocytes and flows in opposite direction in bile ducts
- Blood and bile to not mix, are not within sma structure
Describe zone 1 of the portal acinus
- Closest to portal tract
- Receives most oxygenated blood
- Susceptivble to direct acting toxicants
Describe zone 3 of the portal acinus
- Furthest away
- Receives least blood
- Highest biotransformative/detoxification activity
- More P450 cytochrome enzyme present (metabolises toxins)
- More susceptive to hypoxic injury
- Injury by toxic substances that are metabolically activated by P450
Name the 4 main cell types found in the liver
- Hepatoytes
- Endothelial cells
- Kupffer cells (sinusoidal macrophages)
- Ito cells (hepatic stellate cells
Where are Ito cells found?
- Between endothelial cells adn hepatocytes may have space of Disse
- Ito cells found in this space
Describe the morphology of hepatocytes
- Polyhedral
- Round nucleus
- Prominent nucleolus
Describe the functions of the hepatocytes
- Most hepatic functions
- Metabolise and store minerals absorbed from small intestine
- Secrete bile
Desribe the morphology of Kupffer cells
Macrophage like
Describe the functions of Kupffer cells
Defend against vascular-carried pathogens and remove debris
Describe the morphology of Ito cells
- Contain big intracytoplasmatic vacuoles (lipid)
- Nucleus at periphery
Describe the functions of Ito cells
- Involved in tissue fibrosis
- Involved in retinol metabolism (store vit A)
Describe the biliary tree in the liver
- Bile canaliculi are intercellular channels formed between adjacent hepatocytes, isolated by occluding junctions
- Canals of Hering between the bile canaliculi and bile ducts
- Drainage is from bile ducts of portal tracts
Describe the function of smooth endoplasmic reticulum in hepatocytes
- Contains main enzyme of detoxification (cytochrome P450)
- Involved in lipid and glycogen metabolism
Desribe the function of peroxisomes in hepatocytes
Contain enzymes involved in detoxification (catalase)
Describe the function of the rough endoplasmic reticulum in hepatocytes
- Binds ribosomes engaged in translating mRNA to proteins
- Protein and lipid modifications
Describe the function of the golgi apparatus
- Associated with protein secretion (important for bile secretion)
- Involved in protein and lipid modifications
Describe the function of mitochondria
Aerobic energy supply (ATP production)
Describe the function of lysosomes in hepatocutes
Digestion of macromolecules
Describe the function of glycogen
Short term storage of glucose
Describe the function of lipid droplets in hepatocytes
Storage of esterified fatty acids
What is the function of the gall bladder?
Storage, concentration and release of bile
What is the function of bile?
- Fat digestion
- Hepatic excretion
What are the histological layers of the gall bladder?
- Mucosa (epithelium, lamina propria)
- Muscular layer
- Adventitia/serosa
- NO MUSCULARIS MUCOSAE OR SUBMUCOSA
Describe the structure of the gall bladder
- Fibromuscular sac lined by simple columnar epithelium
- Folds if not distended
Describe the role of the liver in detoxification of foreign chemicals
- Exogenous matter
- Dose makes poison (anything toxic in right amount)
- Liver can identify and detoxify chemicals that are in excess of normal
- Turn over of drugs in body controlled by cytochrome P450
- Hydrophilic drugs excreteed easily
- Hydrophobic go to liver, CYPs add reactive handle so can be acted on (phase 1)
- In phase 2 conjugated handle worked on to make it polar and be excreted
Describe the removal of endogenous waste in the liver
- Haem breakdown in macrophages
- Damaged RBCs taken up by macrophages, haem portion and globin portion
- From globin portion derive amino acids
- High quantitiy of bilirubin produced, goes to bile, excreted by liver
- Iron stored as ferritin and can be reused
- Albumin transports things in blood, conjugates with bilirubin and takes it to liver
- Secreted via bile
- Small amount of urobilinogen reabsorbed from SI, most excreted
Describe the role of the liver in nitrogen excretion
- In absortpive state and post-absorptive state ammonia needs to be dealt with
- AA produced, excreted as urea
- Ammonia toxic, excreted a urea
- Shuttled back to liver by hepatic portal vein
Describe the role of the liver in energy metabolism and homeostasis
- Central control of metabolism
- Without cannot maintain homeostasis
- Glycolysis, gluconeogenesis, glycogenolysis etc all take place in liver
- Maintain blood glucose levels
Describe the clinically important liver enzymes
- Aspartate aminotransferase (AST)
- Alanine amio transferase (ALT)
- Compare ratios of these to asses liver function
List the important plasma proteins
- Serum albumin
- VLDL, HDL
- Fibrinogen and prothrombin
- Transferrin
- Complement proteins
What is the role of serum albumin?
- Highly abundant
- Carrier protein for anything that needs to travel in blood stream but is too small to do so itself
- Maintains osmotic pressure
- Synthesised exclusively by hepatocytes
- Hypoalbuminemia not specieif for liver disease
What is the role of fibrinogen and prothrombin
Needed in coagulation cascade
Describe the role of transferrin
- Iron transport
- Produced in liver to an extent but mostly elsewhere
Describe apolipoproteins
- Each lipoprotein has own set of apolipoproteins
- Are functional proteins
- Activate enzymes
- Bind receptors
- Stabilise lipoprotein
Describe amino acid metabolism in the liver
- Used in urea cycle
- Ornithine takes up ammonia molecule, form scitrulline via carbomoyl phosphate, conversion back through arginine = ornithine and molecule of urea
- Not used in fish or birds
Describe the role of the liver in lipid metabolism
- Bile sats needed to produce smaller fat droplets
- Produced in liver
- Form amphipillic micelles with lipidcore, water soluble exterior
- Once larger made smaller have action of pancreatic lipase
- Degradationof products and produce micelles
- Pores on these micelles allow monoglycerides and FFAs to be released into enterocyte to be absorbed by gut
- TAGs resynthesised and form chylomicrons within enterocytes
Desribe the role of the liver in cholesterol production
- 3 carbon molecule ACA converted to 6 carbon mevalonate via HMG-CoA (enzymatic process)
- Mevaloate loses a carbon by decarboxylation => 5 carbon isoprene
- 30 carbon squalene produed by joining these
- Goes on to form cholesterol via lanosterol
- Once C6 produced commited to cholesterol production
How do statins prevent cholesterol production?
- Prevent reduction from C3 to C6 molecule
- Once C6 produced, commited to cholesterol production
Where on the cholesterol structure are steroid hormones modified?
Carbon 17
List substances synthesised by the liver
- Cholesterol
- Glycogen
- Bile acids
- TAGs
Describe the role of the liver in immune regulation
- Kupffer cells
- Complement synthesis and metabolism
- Line walls of sinusoids
- Mostly for breakdown of RBCs
- Also pick up bacteria and otehr particles absorbed from gut
- Screen and stop bacteria entering systemic circulation
What molecules are stored in the liver
- Glycogen
- Water soluble vitamins
- Fat soluble vitamins
- Iron
Desribe the role of the liver in the production of clotting factors
- Liver synthesises all coagulation factors except VIII (Von Willebrand’s)
- Among these are vitamin K-dependent factors (2, 7, 9, 10)
- Also synthesises inhibitors of coagulation and fibrinolysis and fibrinolytic proteins
- Clears and catabolises activated coagulation factors, plasminogen activators adn breakdown of products of fibrinolysis such as fibrin degradation products
