Liver Flashcards
What are the main properties of the liver
. Second largest organ in the human body ( after skin )
. Make up 2-3% body mass = heavy and large organ ( 3 pounds)
.It accounts for 20-30% of the total oxygen consumption-very metabolically active
. Filters 1.4L blood every minute
How many lobes does liver have
2
(Ieft and right)
Although if you lift liver, look from back = 4 lobes ( 2 smaller lobes = cordate lobe and quadrant lobe = but most are 2 main lobes
Where is liver located
Below diaphgram
What is a liver a place of
Where old rbc’s are broken down.
Each rbc has life span of 110 days - after, body breaks them down and processes them
What is role of phagocytic cells in liver
Recruit dysfunctional rbc’s from circulation - breaking them down
Why is detoxification and elimination of toxic substances important in liver
- Make sure everything coming from digestive tract isnt infected as primary source of infection is what we injest and take in, gut is full of bacteria - dont want in systemic circulation
- Bacteria taken in through diet, waste products generated through food consumption, toxins produced, natural drugs, prescription medication long term = liver failure
SO IMMUNE SURVEILLANCE CELLS IN LIVER KEEP US CLEAN
What are the main functions of the liver
. Metabolism
. Uptake of nutrients delivered from the digestive tract via portal vein
- Temporary nutrient storage ( glucose-glycogen). Synthesis, storage, interconversion, and degradation of metabolites ( nutrients taken in )
- The regulated supply of energy - rich intermediates and building blocks for biosynthetic reactions
. Vitamin storage ( maintains Fe reserve )
. Produces coagulation factors
. Detoxification - removal of toxins from blood/toxic substances - excretion of substance with bile, urine, faeces
.Bile production -from breakdown of rbc’s - produce bile salts - digestion of lipids
. Kupffer cells ( macrophages ) - lining vessels of liver
What does liver do
Maintains the bodies chemical and metabolic homeostasis - keeps everything at ultimate level
What are coagulation factors
Proteins continuously flowing around blood plasma ready to form clots when injury = dont bleed to death
Why have a mineral and vitamin storage
Just incase go through starvation period = reserves
Due to continous flow in of molecules - factory -turn them into other building blocks of life - make new amino acids,sugars and cholestrol - pumped out into blood to other cells
What are most of the toxins
Lipid based - so 1st turn them into water loving molecule = changes properties of molecule
What is the main mineral liver store
Iron
What are the main exit routes for excretion of substances
- Bile
- Urine
- Stools - faeces
What are the 2 lobes in the liver separated by
Falciform ligament- separates the lobes and holds liver in place suspended below diaphragm - holds them apart from each other, makes connections with diaphgram
What does each lobe contain
Lobule
What is a lobule
Little hexagonal structures composed of blood vessel , bile canaliculi , blood vessels come together to form sinusoid
What are lobules comprised of
Hepatocytes which are specialised cells and surrounded by reticular fibre. Main cells in liver
What else is found in the liver
- Connective tissue support - thin connvective tissue capsule
- Interlobual spaces - support blood vessels and bile ducts
- Reticular fibres - collagen III - lots of proteoglycan ( flexibility - space out collagen fibres as water loving ) - around hepatocytes
Where do lobes sit
Below diaphgram
Why are livers large and heavy
Don’t want it slumping down onto gut otherwise its force all stool out of you - suspended in place
Where does blood come in and out in the liver
Blood in through portal vein and Hepatic artery
Blood out through Central Vein
Where do blood from portal vein and hepatic artery mix
In hepatic sinusoids
What is bile secreted by and where does it leave
Through bile ducts
Bile flowing in opposite direction. Hepatocytes secrete bile fluid and runs back towards corner points and exits through bile ducts
What is role of hepatocytes
Take up nutrients and healthy O2 supply
What does liver need
Healthy supply of blood
What is the process of dual blood supply into liver
- Oxygen rich blood flows from the hepatic artery from the aorta - need about 30/40% O2
- Nutrient rich oxygen poor blood from portal vein that comes from digestive system
These flow past hepatocytes
HEPATIC ARTERY - O2 BLOOD
PORTAL VEIN - NUTRIENT RICH BLOOD
What is the hepatic artery
Direct branch off the abdominal aorta
What shape is lobule
Hexagonal
What colour is liver and why
Dark brown
Due to high density of blood vessels surrounding it
When blood mixes = hepatocytes are red and produces bile which runs opposite direction back out corner of lobule
Structure of hepatocytes
- Run through each liver lobule and sinusoids and exit out through central vein
- Have direct surface opposing blood vessel directly = lots of capillaries though
- Microvilli to increase surface area
- Adjacent hepatocyte cells have tight junctions to prevent fluid flowing between hepatocytes
- Bile canaliculi run between hepatocytes
What does each lobule have
Incoming portal vein and hepatic artery at each corner of hexagon - flow inwards
What runs through middle of each lobule and what happens here
Central vein
Blood exits here
What is at each corner of hexagon that makes up lobule and what does it form
Blood vessels Portal vein Bile duct Hepatic artery TOGETHER forms PORTAL TRIAD - 6 per lobule, 1 in each corner, shared with lobuls next to it.
Structure of hepatic sunusoids
- They are blood vessels made up of endothelial cells
- They are fenestrated - allow easy flow of plasma but not erythrocytes
What separates hepatocytes and hepatic sinusoids ?
Vasculature Disse’s space
What’s Disse’s space ?
Separates hepatocytes and hepatic sinusoid and contain plasma and dendritic cells
Function of dendritic cells
- Immune cells - sit it in Disse’s space
- Activate rest of immune system
- Detect if anything in there that could indicate infection in there
- Send out chemical messengers - recruit rest of immune system starting with neutrophils and lymphocytes later
Function of kupfer cells
- Perform phagocytic function to remove protein complexes and small particles from the blood
- They also perform immune surveillance against toxic material from the gut and pathogens from the intestinal flora
- Immune cells which are inside of synocoids
Carbohydrate metabolism in liver
- Store excess glucose as glycogen ( glycogenesis )
- Break down of glycogen to glucose ( glycogenolysis )
- Convert galactose and fructose to useable glucose
- Gluconeogenesis - formation of glucose from other molecules ( non carbs ) i.e. use keto acids
What is liver main place for
Where you can store xs carbs, xs glucose in form of glycogen
What happens during glycogenolysis and glycogenesis
Glycogenesis - xs sugar detected in systemic circulation, taken out and stored as glycogen in liver, under chemical signal of insulin
Glycogenolysis - low levels of blood glucose can send signal to release glucagon = breakdown of glycogen to glucose = increase glucose in systemic circulation
What is the glucose buffer
- high blood glucose level - liver - glycogen formation - normal blood glucose
- fall in blood glucose level - liver - glycogenolysis - normal blood glucose
Function of glucose buffer
Regulates amount of free floating glucose in body
Why do you need to regulate amount of glucose in body
Any change in systemic blood glucose levels = toxicity of cells around body = diabetes - misregulation of blood glucose levels
What happens when high glucose levels in blood
Endothelial cells dysfunction = microvascular diseases e.g. diabetic retinography - leaking blood vessels in retina.
Also direct effect on neurons in body, high glucose levels can kill off neuron - scotomas in vision as you kill of retinal ganglion cells
Why do we need glucose
- Brain uses glucose as main energy source - as it doesnt have capacity to do gluconeogenesis itself
- Red blood cells rely on glucose as their only energy source - cant produce glucose themselves as glucose is the only energy source
How much reserves of glucose is there in glycogen stores and what is the daily requirment
- Glucose reserve of 190 g in glycogen store
- Need 160 g glucose to function = depleted all glucose reserves
What does gluconeogenesis ensure
- Helps maintain systemic glucose level in liver so brain and muscles have sufficient supply to meet demand
- Provides an alternative pathway to produce glucose from carbon skeletons to keep brain going when demand exceeds glucose stores
Substrates can be amino acids, glycerol, lactate
i.e Amino acids - keto acids - glycerol
What is process of triglyceride breakdown
triglyceride + water ———-> 3 fatty acid + glycerol
fatty acid - beta-oxidationto produce ATP - for metabolism
glycerol - gluconeogenesis to produce glucose - by producing C skeleton
Triglyceride separates fatty acid chain from glycerol
Process of lipid metabolism in the liver
. Anabolism : turn lipids into other things to build storage structures
- synthesis of cholesterol ( in liver from lipids ) and fatty acids
- synthesis of lipids from carbohydrates and amino acids ( lipogenesis )
. Catabolism - beta oxidation of fatty acids to produce ATP
What is lipogenesis
Take xs glucose and turn it into fatty acids stores through lipogenesis
Process of protein metabolism in liver
- Liver is the primary site of deamination of amino acids - oxidative deamination = produce NH3, urea cycle in liver, urea out into blood
- Ammonia is turned into urea through urea cycle
- Interconversion of amino acids ( transamination )
- Site of plasma protein synthesis
What vitamins does liver store
. vitamin A ( 10 month store ) . vitamin D ( 4 month store ) . vitamin B12 ( 1 year store ) . vitamin E and K . Folate
What is main mineral stored in liver
Iron
How is iron stored in liver
- Iron stored as part of the molecule ferritin in the liver
- Iron in blood bound transferrin - binds with apoferritin in liver to form ferritin .
What happens when blood iron levels fall
Ferritin releases free iron to bind to transferrin in blood
Where does most VitD come from
Activation of molecules after UV exposure - summer - enough to keep going in winter = good supplement to take in winter
What is VitA essential for
Vision and a lot of processes
So have capacity to store for long time in case theres deficiencies in diet
What is Vit B12 a source of
Meat - not in plant
If low in B12 - skin conditions e.g. eczema
What can VitA act as
Mutagen
During development - if very high levels of vitA -interrupts with lot of signalling pathways required for formation of limbs/proper head
So when pregnant - dont eat liver due to it having high levels of vitA - shouldn’t be consuming any xs during gestation of fetus - mutation in baby and stop taking multivitamins when pregnant
What coagulation factors does the liver produce ?
- factor 10
- factor 9
- factor 7
- fibrinogen
- prothrombin
Why are factor 10,9 and 7 important
Activation proteins that activate clotting
Factor 10 also involved in inactivation of other parts of immune system - directly kill of pathogens from pore in cell surface of bacteria and kill it or act as signalling molecule - bind to protein secreted by pathogen
Why are fibrinogen and prothrombin important
Clotting process in wound heeling due to inflammation
What is coagulation factor
Protein free floating in blood, activated through different pathways
What happens during liver detoxification
Hepatocytes convert toxins into non-toxic metabolites which can be excreted from the body
What toxins do our bodies deal with each day
- Breakdown products from hormones and neurotransmitters
- Drug
- Pollutants
- Insecticides and pesticides
These pass across, enter blood stream and filtered out by liver
What are the 2 primary classes of chemical compound ( toxin )
- hydrophilic ( dissolves in water ) polar : can be excretes in bile or urine - easy to get rid of, liver doesnt have to do much
- lipophilic ( dissolves in lipids ) non-polar : must be converted to hydrophilic to be excreted by bile, urine or stool
What is liver detoxication performed by
Hepatocytes
What are the two phases of converting lipophilic into hydrophilic ?
phase 1 : functionalisation
phase 2 : conjugation
What happens in phase 1 functionalisation ?
- Enzymes : oxidoreductases e.g. cytochrome P450 and hydrolases introduce reactive/polar groups into toxins chemical structure
- Some become polar positive and are excreted through the kidney
- Others are now reactive but need further metabolism and enter phase 2
= SPECIFIC ENZYMES PUT IN POLAR GROUPS ONTO CHEMICAL STRUCTURE - MAKE IT HYDROPHILIC
What happens in phase 2 conjugation ?
- Reactive molecules undergo conjugation reactions
- This makes them stable ( non-reactive ) but water soluble ( hydrophilic ) can be excreted via urine , bile and stool - end up with hydrophilic compound in end
What are 2 pathways of conjugation
Sulfation - Adding sulfur groups
Acetylation -Adding acetyl groups
What does phase 1 leave you with
Functionalised molecule thats now reacted
Why do we need massive reserves of nutrients in the liver
For metabolism
What does bile contain ?
. water . cholesterol . bile salts . buffering ions ( bicarbonate ) . bile pigment ( bilirubin and biliverdin )
What is pH and colour of bile
PH 8
greeny yellow in colour
Function of bile
- Secreted into duodenum
- Aids in digestion of fats
Where does bile flow through when made by hepatocytes ?
- Flows through bile canaliculi between cells
- Flows into common bile duct
- Stored in gall bladder
What is secretion of bile into duodenum controlled by ?
- Hormones : secretin , gastrin and somatostatin
- Vagus nerve
Where are kupffer cells found and what is its function
- Adherent to sinusoidal epithelial cells inside the sinusoid
Resident liver macrophages
Perform scavenger and phagocytic functions to remove protein complexes, small particles, senescent red blood cells, and cell debris from the blood
Also perform immune survelence against gut -derived toxic materials, incuding endotoxin LPS and pathogens from intestinal flora
