Liver and its Functions Flashcards
What divides the liver into 2 lobes?
→ Falciform ligament
What is the biliary tree?
system of ducts to transport bile out of the liver into small intestine
Where is the blood supply of the liver from?
→ Portal vein - Blood returning from the GI tract
- 75%
→ 25% - hepatic artery
Where do the central veins of the liver lobules drain?
→ Into the hepatic vein
→ Back into the vena cava
What do hepatocytes do?
→ 60% perform most metabolic functions
What do Kupffer cells do?
→ 30% types of tissue macrophages
What cells other than hepatocytes and kupffer cells does the liver have?
→ Stellate
→ Endothelial
What is the functional unit of the liver?
→ Hepatic lobule
→hexagonal plates of hepatocytes around central hepatic vein.
→at each of 6 corners is triad of branches of portal vein, hepatic artery and bile duct
What is around the central hepatic vein?
→ Hexagonal plates of hepatocytes
→ At each of the 6 corners is a triad of branches of the portal vein, hepatic artery and bile duct
Where does blood enter the lobules from and flow to?
→ Branches of the portal vein and hepatic artery
→Flows through small channels called sinusoids that are lined with hepatocytes
→ Hepatocytes remove toxic substances from the blood
→ Blood exits the lobule through the central vein
→ Blood flows in opposite direction to the bile
What is the oxygenation like at the hepatic artery?
→ Oxygen rich
Why does blood leaving the lobule have low levels of O2?
→ Hepatocytes near the sinusoids have used up the O2
Describe the flow of bile
→ Bile is secreted by hepatocytes → Series of channels between cells (canaliculi) →Small ducts → Large ducts → Anastomose onto common bile duct
How does the livers microstructure support its role?
→ Large SA - exchange of molecules
→ Sophisticated separation of blood from bile
→ Specific positioning of pumps to achieve localization of materials
How is portal blood filtered?
→ Through the sinusoid - removal of gut bacteria
What is bile?
→ Complex fluid : Water, electrolytes + mix of organic molecules
→ Organic molecules : bile acids, cholesterol, bilirubin + phospholipids
What are the functions of bile?
→ Essential for fat digestion + absorption via emulsification
→ Bile and pancreatic juice neutralize gastric acid as it enters the small intestine
→ Elimination of waste products from blood - bilirubin + cholesterol
→ 500mg of cholesterol converted to bile acids per day
Describe how bile gets to the gall bladder
→ Bile from hepatic ducts
→ Common bile duct
→ Duodenum or diverted via cystic duct
→ Gall bladder
→ Concentrated and stored (30-50ml)
→Released by cholecystokinin in response to presence of fat in duodenum
Causes contraction of gall bladder and relaxation of the sphincter
How is entry of bile into the duodenum controlled?
→ Opening of the sphincter of Oddi
What is bilirubin?
→ Yellow pigment formed from the breakdown of Hb
→ Useless and toxic but made in large quantities so must be eliminated
How are aged RBCs destroyed?
→ Dead/ damaged RBCs are digested by macrophages throughout the body
→ Fe is recycled
→ Globin chains are catabolized
→ Hb cannot be recycled so it is eliminated into bilirubin
How is bilirubin formed?
→ Heme is converted into free bilirubin in a series of steps
→ Released into the plasma and it is carried around bound to albumin
→ Free bilirubin is absorbed by hepatocytes and conjugated with glucuronic acid
→ Conjugated bilirubin is secreted into bile and metabolized by bacteria in the intestinal lumen
→ Eliminated in feces + urine
→Unconjugated bilirubin is conjugated to glucuronic acid
What is the major metabolite in feces?
→ Stercobilin
What is the major metabolite in urine?
→ Urobilin and urobilinogen
How is jaundice caused?
→ Excessive quantities of free or conjugated bilirubin accumulate in ECF
What are the symptoms of jaundice?
→ Yellow discolouration of the skin, sclera and mucous membranes
What is green jaundice caused by?
→ mutation of biliverdin reductase
facilitates the conversion of biliverdin to bilirubin
What is pre hepatic jaundice?
→ excessive RBC breakdown
→ Excess unconjugated bilirubin is not excreted & remains in circulation
→Can be treated with phototherapy- causing isomerisation of bilirubin
→RBC are broken down after birth to have adult haemoglobin
What is hepatic jaundice?
→ Hepatocyte damage
→Excess conjugated &/ unconjugated bilirubin
What is post hepatic jaundice?
→ excess conjugated bilirubin
→ Obstruction into passage of duodenum
→ Enters circulation & into urine
→ pruritus(itch)
What is used for neonatal jaundice in low resource countries?
→ Sunlight canopies
→Filters out most of the or sunburn. ray (UVA, UVB, UVC, IR etc) but allows therapeutic blue light to pass through » decreases risk of over-heating
What toxic substances does the liver metabolize?
→ bilirubin
→ ammonia
→ hormones
→ Drugs & exogenous toxins
How are steroid hormones inactivated?
→ By conjugation & excretion
Why is accidental overdose common with paracetamol?
→ Narrow therapeutic index
How can accumulation of fats in the liver be alleviated?
→ By secreting lipids into the blood
What can be an effect of impaired detoxification?
→ Gynecomastia
→Enlargement of breast in men due to oestrogen accumulation
What blood clotting factors are made in the liver?
→ Fibrinogen
→ Prothrombin
→ V, VI, IX, X, XII
What is needed to make all the clotting factors?
→ Vitamin K
→Vitamin K is essential for formation of pro-thrombin and factors II,VII, IX & X
Converted within liver
The reduced Vit K is oxidised by carboxylase
Warfarin will block conversion of oxidised Vit K to reduced form
What do stellate cells act as?
→ Important deports for storage of fat soluble vitamins (A,D,E,K)
What does liver dysfunction lead to?
→ Fat malabsorption
→ Vitamin deficiency
What vitamin does the liver store?
→ Vitamin B12
→ Folate
What happens with a vitamin B12 deficiency?
→ Pernicious anaemia
How is iron stored in the liver?
→ As ferritin
How is bile secreted?
By hepatocytes:
synthesize bile salts, cholesterol & other organic constituents)
By epithelial cells lining bile ducts:
produce large quantity of watery solution of Na+ & HCO3-stimulated by hormone Secretin in response to acid in duodenum.
Formation of bile acids…
→Cholesterol is converted into bile acids cholic & chenodeoxycholic acids.
→primary BAs are conjugated with amino acids glycine and to a lesser degree taurine in humans.
→This increases solubility, minimises passive absorption, and makes the BAs resistant to cleavage by pancreatic carboxypeptidase
→Exist as Na+ salts in intestine bile salts
→Bacterial metabolism in intestines- Secondary Bile Acids
What is spider angioma?
→ an enlarged blood vessel in the skin (resembling the body of a spider), from which smaller blood vessels extend resembling the spider’s legs.
→more than five is indicative of liver damage.
How do gallstones arise?
Imbalance in the chemical make-up of bile inside the gallbladder leads to gallstones.
→Gallstones can form anywhere along the biliary tract
What are the two types of gallstones?
Cholesterol (80%) & Pigment (20%)
Describe cholesterol gallstones
Risk factors cholesterol stones:
High fat diet
increased synthesis of cholesterol
Inflammation of GB epithelium changes absorptive characteristic of mucosa.
excessive absorption of H20 & bile salts cholesterol concentrates.
What are the risk factors of pigment gallstones?
Risk factors = obesity, excess oestrogen (e.g. during pregnancy), HRT
What is the enterohepatic circulation of bile acids?
traverse the hepatocyte and are actively secreted into canalicular bile,
What forms the protective barrier?
→Kupffer cells-found in sinusoids
Represent approx 80% of all fixed tissue macrophages
→function as mononuclear phagocyte system (MPS)
→exposed to blood from gut that contain pathogenic substances.
→clear gut-derived endotoxin from portal blood
What happens after partial hepatectomy?
(removal of 70% of liver) or in response to toxic injury, they rapidly re-enter cell cycle and proliferate
→regeneration is rapid and proliferation stops once the original mass of the liver is established
What types of cells are involved in liver regeneration?
Does NOT involve liver stem cells or progenitor cells, but replication of mature functioning liver cells
What are the two pathways of liver regeneration?
Growth-factor mediated pathway → most important HGF (hepatocyte growth factor) and TGFα (transforming growth factor alpha)
Cytokine signalling pathway using IL-6 via TNFα binding to its receptor on Kuppfer cells
What is the role of lipopolysaccharides in liver regeneration?
→upregulated after liver injury or hepatectomy and reach the liver through the portal blood supply
→They activate hepatic non-parenchymal cells
→increase the production of tumour necrosis factor (TNF) and interleukin (IL)-6.
Describe the mechanism of liver regeneration
→increase in the production of tumour necrosis factor (TNF) and interleukin (IL)-6 by LPS.
→insulin, epidermal growth factor; EGF norepinepherine, hepatocyte growth factor; HGF. →Cooperative signals from these factors allow the hepatocytes to overcome cell-cycle checkpoint controls and move from G0, through G1, to the S phase of the cell cycle.
→leads to DNA synthesis and hepatocyte proliferation.
→TNF-alpha is blocked until synthesis is completed
What is the purpose of liver function tests?
→Screen for liver infections, such as hepatitis
→Monitor the progression of a disease, such as viral or alcoholic hepatitis, and determine how well a treatment is working
→Measure the severity of a disease, particularly scarring of the liver (cirrhosis)
→Monitor possible side effects of medications
What are the most common sections of the LFT?
Alanine aminotransferase (ALT)
Aspartarte aminotransferase (AST)
Alkaline phosphatase (ALP) - enzyme found in bile duct, indicates obstruction in bile flow
Gamma glutamyl transferase (GGT or ‘Gamma GT’) – also indicates obstruction
Bilirubin - jaundice
Albumin - decreased in chronic liver disease/malnutrition
Clotting studies, i.e. prothrombin time (PT) or international normalised ratio (INR) - if low levels of clotting factors are present, the prothrombin time is longer.
What is the cystic duct?
allows bile to flow in and out of the gallbladder for storage and release.
What is the role of sphincter of Odii?
controls entry into the duodenum
What are the pathways of liver regeneration?
Gut-derived factors, such as lipopolysaccharide (LPS), are upregulated and reach the liver through the portal blood supply.
→They activate hepatic non-parenchymal cells (including Kupffer cells and stellate cells) and increase the production of tumour necrosis factor (TNF) and interleukin (IL)-6.
→Other factors are released from the pancreas (insulin), duodenum or salivary gland (epidermal growth factor; EGF), adrenal gland (norepinepherine), thyroid gland (triodothronine; T3) and stellate cells (hepatocyte growth factor; HGF).
→allow the hepatocytes to overcome cell-cycle checkpoint controls and move from G0, through G1, to the S phase of the cell cycle.
→Stellate cells produce hepatocyte growth factor allowing it to move to S-phase
→TNF-alpha is blocked until synthesis is completed
