Introduction to the liver Flashcards
What is the largest gland in the body?
The liver
What is the biliary tree?
o system of ducts to transport bile out of the liver into small intestine
How many lobes is the liver divided into and by what ligament?
- The liver is divided into 2 primary lobes by the falciform ligament
What is the green duct and what does it deliver and into what?
- Green sac is the gall bladder with common bile duct delivering bile into the duodenum.
What does each lobe receive of its own?
Each lobe receives its own blood supply.
Where is approximately 75% of blood supply to the liver from?
- ~75% of blood supply from portal vein
Where is approximately 25% of the blood supply to the liver from?
- ~25% from hepatic artery
Where do the central veins of liver loubles drain into and back to what?
- Central veins of liver lobules drain into hepatic vein and back to the vena cava
What are 2 primary cells of the liver?
– Hepatocytes
– Kupffer cells
– Others are liver endothelial cells & stellate cells
What is the functional unit of the liver?
• Functional unit is the hepatic lobule
What is the hepatic lobule?
– Hexagonal plates of hepatocytes around central hepatic vein
What do hepatocytes perform?
perform most metabolic functions of the liver
What are Endothelial Kupffer cells aa type of?
Type of macrophage?
What are Endothelial Kupffer cells?
phagocytic activity by removing aged/damaged red blood cells, bacteria, viruses and immune complexes
Where doe blood enter through into lobules through and then flows where?
- Blood enters the lobules through branches of the portal vein and hepatic artery, then flows through small channels called sinusoids that are lined with primary liver cells
Blood entering the lobule vs blood leaving the lobule
- The blood entering the lobule (at the hepatic artery, indicated in red) is relatively oxygen rich, but the blood leaving the lobule contains only low levels of oxygen (at the terminal hepatic venule, indicated in blue) because hepatocytes along the sinusoids have used up much of the available oxygen.
Pathway involved in the biliary system?
Bile secreted by hepatocytes ↓ series of channels between cells (canaliculi) ↓ small ducts ↓ large ducts ↓ anastomose onto common bile duct
How does the liver’s microstructure support its roles?(3points)
- Massive surface area for exchange of molecules
- Sophisticated separation of blood from bile.
- Specific positioning of pumps to achieve specific localisation of materials (at a cellular level).
What is portal blood filtered through and what is removed?
- Portal blood filtered through sinusoid removal of gut bacteria /antigens
What happens as blood flows through intestinal capillaries?
- As blood flows through intestinal capillaries it picks up many bacteria from intestine
What is bile?
– Complex fluid = water, electrolytes + mix of organic molecules
What is bile essential for?
– Essential for fat digestion & absorption via emulsification
What does bile with pancreatic juice do and what does it aid with?
– Bile + pancreatic juice neutralises gastric juice as it enters the small intestine aids digestive enzymes
What does bile eliminate?
– Elimination of waste products from blood in particular bilirubin & cholesterol
Where do hepatocytes initially secrete bile and where does it flow afterwards?
– Initially the hepatocytes secrete bile into the canaliculi, which flows into the bile ducts and contains large amounts of bile salts, cholesterol and other organic constituents.
How is bile modified afterwards?
– It is then modified by water and bicarbonate-rich secretion from epithelial ductal cells.
Movement of bile from hepatic duct to the gall bladder
Bile from hepatic ducts ↓ common bile duct ↓ duodenum OR diverted via cystic duct ↓ GALL BLADDER ↓ concentrated & stored (30-50ml)
What is entry into the duodenum controlled by?
- Entry into the duodenum is controlled by opening of the Sphincter of Odii
Where can bile be diverted into and via what?
Bile can also be diverted into the gall bladder via the cystic duct where it is stored and concentrated 5-fold.
What is bilirubin ?
– Yellow pigment formed from breakdown of haemoglobin
What are the properties of bilirubin?
– Useless & toxic but made in large quantities
What gives bile its colour?
– The yellow pigment bilirubin is what gives bile its colour
How are dead/damaged RBC digested?
- Dead/damaged RBC digested by macrophages throughout body
What happens to Fe3+ from dead/damaged RBC’s?
- Fe3+ is recycled
What cannot be recycled from a damaged or dead RBC and therefore what happens to it?
- Haem (porphyrin) cannot be recycled → eliminated
Where is RBC digested predominantly?
- RBC digested throughout the body and predominantly in spleen
What are globin chains and what are they catabolized to?
- Globin chains are proteins and catabolized to various amino acids and then reused
What is haem converted into in a series of steps?
- Haem converted into free bilirubin in a series of steps
What is haem released into and carried around bound to?
- Released into plasma – carried around bound to albumin
What is free bilirubin absorbed by and conjugated with what?
- Free bilirubin absorbed by hepatocytes → conjugated with glucuronic acid
What is conjugated bilirubin secreted into and what is it metabolised by and eliminated into?
- Conjugated bilirubin secreted into bile → metabolised by bacteria intestinal lumen & eliminated into faeces/urine
What is the major metabolite in faeces and therefore what color does it give?
- Major metabolite in faeces is Stercobilin – brown colour
What is the major metabolite in urine and what is the color given off?
- In urine – Yellow urobilin & urobilinogen
What happens to albumin bound bilirubin in order to be absorbed into hepatocytes?
- Albumin-bound bilirubin is stripped of albumin and absorbed into hepatocytes.
Once bilirubin is stripped off albumin, what is it broken down to?
- Part of the bilirubin is broken down to colourless substances
What do hepatocytes produce once part of the bilirubin is broken down and what is it converted into?
hepatocytes produce urobilinogen, and colonic bacteria convert this to stercobilinogen.
What can both urobilinogen and and stercobilinogen be oxidised into?
o Both substances can be oxidised to yellow urinary urobilin and brown faecal stercobilin.
In what cases is renal excretion of urobilin and stercobilinogen increased?
o The renal excretion of urobilin and stercobilinogen is increased in cases of hepatitis and other damage to hepatocytes.
What is jaundice?
• Excessive quantities of either free or conjugated bilirubin accumulate in ECF
What are the symptoms of jaundice?
– a yellow discoloration of the skin, sclera and mucous membranes is observed
What is green jaundice caused by?
o Caused by a mutation of the biliverdin reductase gene
Haemolytic jaundice
- Excessive breakdown of RBC
- Excess unconjugated bilirubin not excreted and remains in circulation
Hepatic jaundice
- Hepatocyte damage
- Excess conjugate or unconjugated bilirubin
Post hepatic jaundice
- Excess conjugated bilirubin
- Obstruction to passage into duodenum
- Enters circulation and into the urine
What is liver vital in and what does it metabolize and excrete?
Liver is vital in the metabolism & excretion of various substances that can be toxic to body:
– Bilirubin
– Ammonia
– Hormones e.g. all steroid hormones (androgens, oestrogens, cortisol, aldosterone, thyroxine)inactivated by conjugation & excretion
– Drugs & exogenous toxins e.g. asprin, paracetamol, ethanol
Where are all steroid hormones and thyroxine inactivated and catabolized?
– All steroid hormones (oestrogen, androgens, cortisol & aldosterone) & thyroxine are inactivated & catabolised in liver
What are most steroids excreteds as?
– Most steroids excreted as glucuronide/sulphate conjugates
What can impairment in liver function lead to?
– Hence impairment in liver function can lead to overactivity of hormonal system
In how many phases does liver metabolize drugs and hormones in?
2 phases
What happens in phase 1 ofwhen the liver metabolizes drugs and hormones?
– Phase 1 (primarily oxidation/reduction) – occurs in smooth ER, catalysed primarily by family of cytochrome P450 enzymes common feature to make substrate into polar compound
What happens in phase 2 of when the liver metabolizes drugs and hormones?
– Phase 2 (conjugation) to make it more water soluble….ie. Glucuronyl is most prevalent
What does elimination occur via?
– Elimination via ATPase pumps
Phase 3 is also possible, what happens?
– The conjugate substance is eliminated into blood or bile using ATPase pumps.
What is paracetamol aka?
• Paracetamol aka acetaminophen
How many phases does paracetamol o/d have?
2 phases
When is paracetamol not to be taken?
Not to be taken after alcohol consumption
What happens in the liver during a paracetamol o/d?
- In paracetamol o/d, the liver enzymes are saturated and glutathione stores rapidly depleted
What are the symptoms on the liver and kidneys after paracetamol O/D?
liver necrosis and damage to kidney by toxic metabolites.
What does paracetamol o/d involve?
o Treatment involves giving N-acetylcysteine, the precursor to glutathione which increases its levels.
How many phase effects does paracetamol o/d have?
Paracetamol o/d has 2 phase effect
What is the first step in the metabolism of alcohol?
oxidation of ethanol to acetaldehyde catalysed by the enzyme alcohol dehydrogenase containing the coenzyme NAD+
Ethanol metabolsim
- The conversion of pyruvic acid to lactic acid requires NADH.
- Pyruvic Acid + NADH + H+ —> Lactic Acid + NAD+
- This pyruvic acid is intended for conversion into glucose by gluconeogenesis, but since most of it gets converted to lactic acid then this pathway is inhibited, which could result in hypoglycemia from lack of glucose synthesis. Also, the excess NADH produced by alcohol metabolism can result in acidosis from lactic acid build-up. - Excess NADH may be used as a reducing agent in two pathways involved in lipogenesis–one to synthesize glycerol and the other to synthesis fatty acids. As a result, heavy drinkers may initially be overweight.
- The NADH may be used directly in the electron transport chain to synthesize ATP as a source of energy. This reaction has the direct effect of inhibiting the normal oxidation of fats in the fatty acid spiral and citric acid cycle. Fats may accumulate or acetyl CoA may accumulate with the resulting production of ketone bodies. Accumulation of fat in the liver can be alleviated by secreting lipids into the blood stream. The higher lipid levels in the blood may be responsible for heart attacks.
What is excess acetaldehyde itself and what does it lead to?
The excess acetaldehyde itself is toxic to the liver leading to hepatitis and cirrhosis
What condition is the alcohol flush reaction and due to what reason does it occur?
- Alcohol flush reaction is a condition in which the face and/or body experiences flushes or blotches, due to an accumulation of acetaldehyde
What can acetaldehyde accumulation be caused by?
- The acetaldehyde accumulation can be caused by a missense polymorphism that encodes the enzyme, acetaldehyde dehydrogenase (ALDH2)
What is ALDH2 normally responsible for?
normally responsible for breaking down acetaldehyde, a product of the metabolism of alcohol
Liver problems caused by alcohol (Fatty liver)
o Alcohol abuse can lead to the accumulation of fat within the liver cells.
Liver problems caused by alcohol (Alcoholic hepatitis)
o Excessive use of alcohol can cause acute and chronic hepatitis (inflammation of the liver).
Liver problems caused by alcohol(Alcoholic cirrhosis)
Common causes include excessive alcohol intake, chronic hepatitis B and C infection, intake of certain chemicals and poisons, too much iron or copper, severe reaction to drugs and obstruction of the bile duct
What are the effects of impaired detoxification?
- Gynecomastia
What is gynecomastia due to?
due to alcoholic cirrhosis
What do blood clotting factors include?
– Fibrinogen
– Prothrombin
– Nearly all the other factors e.g. V, VI, IX, X, XII
What is vitamin K essential for the formation of?
- Vitamin K is essential for formation of pro-thrombin and factors II,VII, IX &
What can happen to blood clotting factors in severe liver disease?
in severe liver disease, excessive bleeding may result due to lack of these factors.
What are hepatocytes important depots for?
• Hepatocytes (stellate cells in particular) are important depots for storage of fat-soluble vitamins D, K, E and Vit A
What does liver dysfunction eventually lead to?
– Liver dysfunction ⇒ fat malabsorption ⇒ vitamin deficiency
What specigic vitamin B does the liver store and how long does it last?
• Stores Vit B12 and enough stored to last 2-3 years
What does Vit B12 deficiency lead to?
– Vit B12 deficiency ⇒ pernicious anaemia
The liver stores folate which is required in what?
Liver Stores folate, which is required in early pregnancy.
What is Iron stored as in the liver and when can it be released?
• Iron is stored as ferritin, which can be released when needed (blood-Fe buffer)
When may vitamin deficiency occur?
• Vitamin deficiency may occur when there is malabsorption of fat due to liver dysfunction
What do hepatic cells contain large amounts of, and what do they combine reversibly with?
• Hepatic cells contain large amounts of apoferritin protein, which combines reversibly with Fe (when in excess) to form ferritin, until needed.
What does ferritin release when Fe in circulating body fluids is low?And hence what does it act as?
• When Fe in circulating body fluids reaches low level, the ferritin releases Fe. Hence acts as a blood iron buffer as well as storage system.
