Liver anatomy and function Flashcards
the liver
- is your largest solid organ
- 1/50 th of your body weight
- located in right upper quadrant
- composed of 2 lobes separated by the falciform ligament
Variations in gross liver anatomy
Genetic variations – hereditary anatomical displacement, accessory lobes
Internal factors – portal thrombosis, cardiac cirrhosis, fibrosis and atrophy
External factors – impression effects (diaphragm, tight belts/corsets, coughing/emphysema)
Riedels and accessory lobes and Clefts or Fissures
Lobular atrophy
the liver can be divided into functional bits
Liver can be divided into segments
Based upon blood supply and bile drainage
Each segment has an independent system
Important for ………..*
Within each segment the tissue can be
Divided into lobule/ acinus –
the functional units of the liver
These are composed of :
plates of hepatocytes
sinusoidal channels
Inlet and exit blood vessels
bile canaliculi
the liver has an unusual blood supply
Portal vein – venous blood from gut (75%)
Hepatic artery – arterial blood (25%)
Estimated 25% of cardiac output enters
liver (1.3L+/min).
Blood content up to 30% of liver weight
and up to 15% of total blood content
Blood enters, mixes in the sinusoids and
drains via hepatic veins into the IVC near
the right atrium
Liver stroma
Connective Tissue – capsule
perivascular
portal tract
reticular network
Composed of ECM materials – dynamic and complex macromolecules
mainly collagens (I, II, III, IV, V and VI) produced by stellate cells
Half life 30 days, hydroxyproline produced as metabolite (MMPs)
Glycoproteins (FN, LN etc) link cells to collagen/ECM
Bidirectional communication between cells - integrins
liver ECM modifies cellular function
lobule or acinus ?
acinus - centred on portal tracts
lobule - centred on central veins
portal space - branches of portal vein , hepatic artery and bile duct
fibrosis and cirrhosis lead to disruption of lobular architecture
Hepatocytes
60-65 % of liver tissue
100 billion cells
Polarised polyhedral epithelial cells
20-30uM
Low mitotic index
Are the main functional cells
Very versatile
Biliary epithelium
1-3 % of liver tissue
Form collecting vessels of increasing size to collect canalicular bile
Polarised cuboidal or columnar epithelial cells
Dense basement membrane
Transport properties
Secretion
biliary epithelium vary in size and can be targets of disease
Endothelium
Squamous epithelial cells
Line the hepatic vasculature
Protect the parenchyma from blood cells, bacteria and viruses
Filter fluids
Normal endothelial functions – anti-thrombogenic surface
regulation of coagulation
Selective uptake of solutes and particles
Scavenging of waste products
hepatic endothelial cells regulate immune cell movement into the liver
kupffer cells
Hepatic macrophages located within the sinusoids
80% of all macrophages in the body
Multiple functions including phagocytosis, regulation of the microcirculation,
removal of endotoxin
Very active receptor-mediated endocytosis
Can produce cytokines, present antigen and stimulate immune responses
stellate cells
Also called Ito cells or lipocytes
15% of non hepatocyte cells in liver
Perisinusoidal fat/retinoid storing cells
Star shaped with multiple membrane
processes and branching structure
Can transform to a more fibroblast-like
morphology in disease
digestive functions of the liver
Carbohydrate and fat metabolism
Protein metabolism
Storage of vitamins and minerals
cholesterol synthesis
essential component of cell membranes - establishes proper membrane permeability and fluidity
an important component for the production of bile, acids, steroid hormones ,and vitamin D
Production of bile
About 0.5L produced per day by hepatocytes
Recycled 6-8 times a day…..to recycle bile salts
A few 100ml can be stored in the gallbladder
Released into the intestine on demand
Involved in the emulsification of fat in the intestine
Fat soluble vitamin uptake (A,D,E,K)
Also for excretion of some substances which cant be cleared by kidneys
(cholesterol, bilirubin)
Detoxification functions of the liver
PHASE 1 Metabolism (eg oxidation by P450 enzymes)
PHASE 2 Metabolism (eg conjugation)
CYPs are the major enzymes involved in drug metabolism and deactivation – either
directly or by facilitated excretion from the body.
CYPs are also responsible for bioactivation of some compounds.
Levels vary with age, gender, individual and cell/organ (or even area in organ)
Synthetic functions of the liver
Production of useful proteins :
Albumin (50% of all plasma protein)
Fibronectin and components of the coagulation cascade
Plasminogen
Alpha-1 antitrypsin
Transferrin
Hepcidin
Functions and detox capacity of the liver change with age
cellular changes -
- accumulation of oxidized proteins
- decline in autophagy level
- changes in nuclear volume and vacuolation
functional change
- decline in total bilirubin
- decline in liver specific cytochrome P450
- reduction in bile acid synthesis and bile flow
morphological change
- dark colour due to accumulation of lipofuscin
- loss of volume
- ECM deposition
Immune function of the liver
Protection against pathogen arriving in blood
Phagocytosis of old or dying cells
Innate immune functions
Induction of tolerance
the normal liver contains resident populations of immune cells - There are approximately 1010 lymphocytic cells in the normal liver
Cirrhosis has dramatic and life-threatening complications
- portal hypertension
- ascites
- varices in the oesophagus
-renal failure
the main drivers of cirrhosis in the EU are viral infection , alcohol and metabolic syndrome
Viral Hepatitis
Viruses selectively infect hepatocytes (A-E)
Very strong immune response causes severe hepatitis
The immune system then kills the infected hepatocytes
Some viruses are cleared whilst some cause a chronic
ongoing infection and immune response which drives the
development of fibrosis and end stage liver failure
Viral hepatitis
HBV – up to 0.7% of EU population chronically
infected
Vaccine has helped
But responsible for 30% cirrhosis cases and 15%
primary liver cancer
HCV – up to 3.6 % of EU population chronically
infected
Very long disease course
90% of those infected probably don’t know it
alcohol
Europe is the heaviest drinking area of the world
20% of the EU population (>15 years of age) report
heavy drinking on occasion (5 drinks in a session)
69% of primary liver cancer in France attributed to alcohol
Metabolic associated steatotic liver disease ( MASLD )
More than 50% of adults in EU countries can be considered overweight or obese
Presence of fatty accumulation in greater than 5% of hepatocytes
Ranges from just fat to hepatitis and fibrosis
Increased risk of developing HCC
26% higher health costs for patients with fatty liver disease
Common pathways drive development of fibrosis in the liver
damage -
- virus / infection
- toxin / ethanol
- autoimmunity
