What is the gross anatomy of the liver - anteriorally?
2 lobes - right (60%), left (40%) Gall bladder just below right lobe Falciform ligament is in between RL and LL, holding them both together
What is the Carnegie Stage system?
23 stages providing a unified developmental chronology, covering only day 0-60 of development
How does the liver receive blood?
Dual blood supply - hepatic artery (20), and hepatic portal vein (80 - venous) All drained into inferior vena cava
What is the purpose of blood delivered to the liver by HPV and HA?
HA - deliver O2 and nutrients HPV - brings blood from gut so that it is filtered before entering the circulation
What is the couinaud classification?
8 functionally independent segments - each has a branch of HPV, HA and HV, so each segment is drain and receives its own blood Each segment can be resected without affecting any other segment
What are the different cell types in the liver?
Hepatic cells, endothelial cells, cholangiocytes, kupffer cells and hepatic stellate cells
What are Hepatocytes and non-parenchymal cells?
Kupffer or hepatic stellate cells are flattened dense cell nuclei that appear to be in sinusoids Hepatocytes are large cells with pale rounded nuclei
What are Hepatic stellate cells and what do they do?
Vitamin A storage, activation means ECM production (fibrogenesis) BUT not really active in healthy liver, but they are very important in causing liver cirrhosis as normal healthy tissue has collagen and become fibrotic
What are Sinusoidal endothelial cells?
Fenestrated - allows lipids and other molecules movement to and from hepatocytes
What are Kupffer cells?
Phagocytosis - RBC breakdown Secretion of cytokines - promote hepatic stellate cells activation causing proliferation, contraction and fibrogenesis
What are the micro-anatomy structures?
Morphological - lobules, portal tracts/triads Functional - acinis, blood flow, bile flow
What is the Surface anatomy of the liver?
Liver is just below diaphragm, 2nd largest organ after skin Largely right sided, but apex of liver is on rhs
What are Acinis?
Unit of hepatocytes divided into 3 zones dependent on proximity to arterial blood supply Functional unit which is less clearly identifed
Hepatocytes in which zones are more susceptible to ischemia and viral hepatitis?
Ischemia - zone 3 Viral hepatitis - zone 1
Where is bile produced and where does it flow to?
Produced by hepatocytes and flows in opposite direction to blood, along canaliculus to bile duct - then towards gall bladder and intestine
What is the function of hepatiocytes?
Protein metabolism, carb metabolism, lipid met, detoxification - all of which needs energy from mitchondria
How is protein synthesis and metabolism carried out in the hepatocyte?
RER does synthesis, GA packages for secretion, and deamination of amino acids (amino group to urea cycle and carbon skeleton is reused)
How and where is carbohydrate metabolism carried out in the hepatocyte?
Glycolysis, gluconeogenesis, glycogenolysis, gluconeogenesis Uses SER, mitochondria, cytoplasmic enzymes
How and where is lipid metabolism carried out in the hepatocyte?
Triglyceride metabolism - FA converted to TG and lipoproteins for transport to energy requiring cells; digested TG chylomicron remnants processed into lipoproteins Bile acid production Using SER, peroxisomes and mitochondria
How and where does detoxification occur in hepatocytes?
Metabolise, modify/detoxify exogenous compounds Using Lysosomes and SER
Give an example of a transamination example
Alanine + alpha oxoglutaric acid --> glutamic acid and Pyruvic acid
How does deamiation take place in situ (liver and muscle)?
Muscle releases alanine into blood, taken to liver where it has the amine group removed, leaving the carbon skeleton (which can then be entered into TCA to make glucose) The amine group is very toxic (NH3) so needs to be transformed into urea, which is water soluble, metabolically inert and non-toxic. Urea is then excreted in urine
What is the role of the liver in fat metabolism?
Fat is main energy store in body, stored in adipose and liver tissue - liver can convert excess glucose and a.a. to fat for storage Metabolise fat for energy source, converting FA to acetyl CoA and can turn acetyl CoA to acetoacetate for transport in blood Synthesises cholesterol, lipoproteins, phospholipids
Why is liver disease important?
It affects 2 million people in the UK and incidence is rising 1 in 50 of all deaths
What is the gross anatomy of the liver posteriorly?
4 lobes: Left, Right, Caudate and Quadrate (next to gallbladder)
What are the 2 types of layers of cells that make up the liver in the embryo?
Endoderm (parenchymal tissue), mesoderm (connective tissue)
What is similar about the liver and biliary system development?
They both share a common origin with the ventral part of the pancreas at the distal foregut/proximal midgut
What are the stages 11, 12, 13, 14, 18 and 18-23 in the carnegie stage?
What are the most important carnegie stages in the liver?
Stage 11, day 29 is most important - liver bud develops, and fuses (kind of) with mesoderm Structure from day 40-60 begins to develop By 8 weeks it starts to migrate By 10 weeks moved completely to RHS
From what does the septum transversum arise in embryology?
The mesoderm - gives rise to parts of thoracic diaphragm and ventral mesentry of foregut in developed human
How is each of the 8 lobes in the couinaud classification numbered?
What is the arrangement of the cells in the liver?
What shape is a liver lobule?
Hexagonal and divided into concentric centrilobar, midzonal and periportal parts
What does a liver lobule look like? FITB
What are portal tracts composed of and where are they located?
Around edges of adjoining lobules - composed of arteriole, branch of portal vein and bile duct
How does the blood flow in the lobule?
De-O2, nutrient rich blood from HPV, O2 blood from hepatic artery flow towards central vein Bile flows opposite direction
What happens to the hepatic bud around week 4 of IUL?
Divides in the pars hepatica and pars cyctica
What does the pars cystica develop into?
The gallbladder and cystic duct around 8 weeks
What is the function of the liver?
Biosynthesis, digestion, energy and metabolism, degradation and detoxification
Where does the liver get its blood supply from?
Rich blood supply - dual with 20% from hepatic artery and 80% from HPV Blood from liver drains into IVC from hepatic vein
How does the liver make glucose from lactate?
Uses the Cori cycle which requires lots of energy Eqn: Lactate->pyruvate->glucose
What is the livers function is glucose regulation?
After a meal, with ^ in BGL, glucose is taken up by tissues and is stored as glycogen mainly in muscle and liver Liver breaking down glycogen maintains BGL in between meals
What is gluconeogenesis?
The process of synthesising glucose from non-carbohydrate sources, e.g. via Cori cycle, via deamination
How many kcal per mole of O2 does carbohydrate and fat burn?
Carb - 120kcal per mole O2 Fat - 100kcal per mole O2
What is the role of the liver in protein synthesis?
Synthesises 90% of plasma proteins -> 15-50g/day Synthesis of blood clotting factors Synthesis of dietary non-essential amino acids by transamination
What is the importance of plasma proteins?
Binding/carrier function, plasma COP (oedema)
Why is deamination carried out?
So a.a. can be used as a food source - occurs primarily on glutamic acid because it is the end product of many transamination reactions
What happens to the ketone bodies produced in the liver?
They are water soluble so don't need carriers to reach muscle
What does the liver synthesise as well as lipoproteins?
What is a problem about lipid transport?
It is hydrophobic so needs an aqueous medium - lipoproteins have TG, cholesterol, phospholipid and a protein coat, which stabilises the lipid
What are the different types of lipoproteins?
VLDL - lots of TG LDL - high cholesterol and phospholipids HDL - high protein content
How can cholesterol be synthesised?
Sterol nucleus from acetyl CoA and is used in synthesis in various compounds including steroid hormones and bile salts
How often is bile secreted?
Continually by liver and stored/concentrated in gallbladder
What are the major components of bile?
Bile salts, cholesterol, phospholipids, bile pigments, bicarbonate ions and water - bile is stable solution together
How is bile formed?
What is the function of bile?
Digestion/absorption of fats, excretion of variety of substances via GIT, neutralise acidic chyme from stomach
Where and how is bile secreted?
Released into duodenum during digestion - small amounts during cephalic, gastric phase due to vagal nerve and gastrin In the intestinal phase CCK stimulates gallbladder contraction, relaxing the sphincter of Oddi
How does bile help with digestion and absorption of fats?
Lipids are poorly soluble in water, so there is a 4 stage process -> secretion of bile and lipases, emulsification, enzymatic hydrolysis of ester linkages and solubilisation of lipolytic products in bile salt micelle
What are the 4 stages of lipid digestion using bile? FITB
How are bile salts composed?
Steroid nucleus, with 2 planar faces - amphiteric
What is the structure of micelles?
Hydrophilic head in contact with surrounding solvent, sequestering the hydrophobic tail regions in the micelle centre
What are the functions of micelles?
Important in absorption, presenting the FA and monoglycerides to the brush border
Where is the micelle absorbed?
Bile salts absorbed in ileum, but lipid absorption is complete by middle of jejunum
What happens to the bile salts after absorption?
Transported back to liver for recycling via enterohepatic circulation
What happens to the monoglycerides/FA after absorption by enterocytes?
Resynthesised into triglycerides by 2 different pathways
What are the 2 pathways of resynthesis of triglycerides?
Monoglyceride acylation and phosphatidic acid pathway
What are chylomicrons and what are they composed of?
Lipoprotein particles synthesised in enterocytes as emulsion Made up of 80-90% TG, 8-9% phospholipids, 2% cholesterol, 2% protein, trace carbohydrate
What happens to the chylomicrons after synthesis?
Transported to GA and secreted across basement membrane by exocytosis - they enter the lacteals (too big for capillaries of villi)
How does the enterohepatic circulation help with bile salt reabsorption?
Active reabsorption of bile salts in terminal ileum - also some is lost to bacterial deconjugation/hydroxylation Bile salt recirculated via HPV back to liver where hepatocytes extrat all bile salts present, which are then reconjugated/hydroxylated before reuse
How many times per meal is the bile salt pool secreted?
How does the liver excrete a variety of substances via GIT?
Liver breaks down/inactivates steroid and peptide hormones, which are secreted into bile for excretion (similar role with drugs) Excretory route for excess cholesterol Excretion of bile pigments - bilirubin from haem breakdown
What other functions does the liver have?
Storage of fat soluble vitamins (ADEK) Storage of iron as ferritin Storage of vit B12 Glycogen and fat store Protection - kupffer cells Ca metabolism - UV light converts cholesterol to vit D precursor, which requires 2x hydroxylation to convert it into active form