L7*-Liver cell biology & function & motility

Question 1

Brief explanation of the liver.

Answer 1

-The liver is closely associated with other abdominal organs.
- 1/50th of your body weight
- Liver located in right upper quadrant
- Composed of 2 lobes separated by the falciform ligament.
- Gallbladder is just underneath the liver

Question 2

Tell me 4 different variations in gross liver anatomy. (do I need to know this?)

Answer 2

1. Genetic variations – hereditary anatomical displacement, accessory lobes
2. Internal factors – portal thrombosis, cardiac cirrhosis, fibrosis and atrophy
3. External factors – impression effects (diaphragm, tight belts/corsets, coughing/emphysema) Riedels and accessory lobes and Clefts or Fissures.
4. Lobular atrophy

Question 3

Where does the hepatic drains directly into?

Answer 3

duodenum.
Hepatic bile contains bule acids, cholesterol, bilirubin(waste product from RBCs) that assist in emulsifying fats for absorption.

Question 4

What is the functional unit of the liver and what is it based on ? and what are they composed of within them ?

Answer 4

Lobule/acinus
-liver can be divided into segments. based upon blood supply and bile drainage. within each segment, the tissue can be divided into lobule /acinus.
-These are composed of plates of hepatocytes, sinusoidal channels, inlet and exit blood vessels, bile canaliculi.

Question 5

Describe the unusual blood supply to the liver.

Answer 5

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

Question 6

What contains in the liver stroma( supportive connective tissue framework within the liver) ?

Answer 6

Connective tissue - capsule, perivascular, portal tract, reticular network

composed of ECM materials - dynamic and complex macromolecules, mainly collagen (I,II,III,IV,VI) produced by stellate cells.

half life of 30 dys, hydroxyproline produced as metabolite (MMPs)

glycoproteins (FN,LN) link cells to collagen/ECM

Bidirectional communication between cells - integrins

Question 7

Describe hepatocytes found in the liver.

Answer 7

-60-65& of liver tissue
-100 billion cells
-polarised polyhedral epithelial cells
-20-30uM
-Low mitotic index

-Hepatocytes are the main functional cells of the liver and they are very versatile.
Versatile => hepatocytes can adapt to perform a wide range of essential tasks like metabolism, detoxification, protein synthesis, bile production, immune function.

Question 8

Describe Biliary epithelium in the liver.

Answer 8

1-3% of live tissue
-Form collecting vessels of increasing size to collect canalicular bile
-Polarised cuboidal or columnar epithelial cells
-dense basement membrane
-transport properties
-secretion

Question 9

Describe endothelium in the liver

Answer 9

-Squamous epithelial cells
- Line the hepatic vasculature
- protect the parenchyma from blood cells, bacteria and viruses
-Filter fluids
-normal endothelial functions like anti-thrombogenic surface, regulation of coagulation
-selective uptake of solutes and particles
-scavenging of waste products

Question 10

Describe Kupffer cells in the liver.

Answer 10

-these are the hepatic macrophages located within the sinusoids > filters blood, engulfs pathogens, clearing debris, regulate immune response liver.
-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 response.

Question 11

Describe Stellate cells in the liver

Answer 11

-also called Ito cells / lipocytes
-15% of non hepatocyte cells in liver
- perisinusoidal fat / retinoid storing cells
-star shaped with multiple membrane which processes and branching structure.
- can transform to a more fibroblast-like morphology in disease.

Question 12

Name few general functions of the liver.

Answer 12

-Digestive functions of the liver.
-cholesterol synthesis
-Production of bile
-detoxification functions
-synthetic functions for proteins and other useful proteins
-immune function of the liver

Question 13

Describe the ‘digestive’ function of the liver.

Answer 13

-carbohydrate and fat metabolism
-protein metabolism
-storage of vitamins and minerals

Question 14

Describe the cholesterol synthesis in the liver.

Answer 14

-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.

Question 15

Describe the production of bile in the liver.

Answer 15

-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 can’t be cleared by kidneys (cholesterol, bilirubin)

Question 16

Describe the detoxification functions of the liver. and what are the 2 phases in detoxification in the liver.

Answer 16

-foreign compounds are converted into water soluble then into bile and urine > GENERAL

Phase 1 - metabolism (oxidation by P450 enzymes)
Phase 2 - Metabolism (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.

*metabolism and detoxification levels vary with age, gender, individual and cell/organ.

Question 17

Name any useful proteins synthesised by the liver.

Answer 17

-Albumin (50% of all plasma protein)
-Fibronectin and components of the coagulation cascade.
-Plasminogen
-Alpha-1 antitrypsin
-Transferrin
-Hepcidin

Question 18

Lastly, describe the immune function of the liver.

Answer 18

-Protection against pathogen arriving in blood.
-phagocytosis of old or dying cells
-innate immune functions
-induction of tolerance

Question 19

What complications does Cirrhosis cause in the body ? and what are the 3 main causes of the cirrhosis.

Answer 19

Complications :
-Portal hypertension
-Ascites
-Renal failure
-Varices in the oesophagus

Causes :
-viral infection
-alcohol and metabolic syndrome

Question 20

Describe in detail about Viral hepatitis

Answer 20

-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.

Question 21

Describe MASLD and what does it stand for ? and what other complications can MASLD can bring ?

Answer 21

MASLD - Metabolic Associated Steatotic Liver Disease.
-in people with obese or overweight
-presence of fatty accumulation in greater than 5% of hepatocytes.
-ranges from just fat to hepatitis and fibrosis
-Increased risk of developing HCC-Hepatocellular carcinoma

Complications:-
Obesity, Diabetes, Dyslipidaemia, hypertension, Insulin resistance, Lipotoxicity, Oxidant stress, Apoptosis, Inflammation.