Liver microanatomy

Question 1

Where is the liver located?
What are the 2 basic functions of the Liver?

Answer 1

• In the upper right quadrant of the abdomen deep to rib 7-11
  >An organ that:
• Filters the blood from the GI tract
• Production + exocrine secretion of bile

Question 2

Name and explain the 7 functions of the liver.

Answer 2

1- Fat synthesis and breakdown
Oxidise triglycerides to provide energy
Synthesis of plasma lipoproteins
Synthesis of cholesterol and phospholipid

2- Carbohydrate synthesis and breakdown
Conversion of carbohydrate and proteins into fatty acid and triglyceride
Regulation of blood glucose by glycogen synthesis and breakdown

3- Protein synthesis and breakdown
Synthesis of plasma proteins e.g. albumen and clotting factors
Synthesis of non essential amino acids
Gluconeogenesis
Deamination of amino acids to produce urea

4- Detoxification of drugs and toxins
Alcohol, natural substances e.g. steroid hormones, proteins

5- Storage: vitamins (e.g. B12), minerals (e.g. copper, iron) and glycogen

6- Vitamin D activation

7- Bile synthesis and secretion

Question 3

• What type of blood does the liver receive from the GI tract, From what blood supply?

Answer 3

• Deoxygenated > Via Hepatic Portal vein
  = Rich in: Fat, carbohydrates and proteins
• There may be some toxins

Question 4

What does the liver do to the blood is receives from the GI tract?

Answer 4

1- Breaks fat, carbohydrates and proteins down
2- Detoxifies any toxins or drugs to make them less harmful
- ^ All of these once broken down and safe are returned into the deoxygenated blood to the systemic circulation

Question 5

1- What are the 2 vascular inputs of the liver?
2- What is the 1 venous output of the liver?
> Describe what there function.

Answer 5

1-
- Hepatic artery proper: O2 input to liver, keeps hepatocytes alive allowing to function as specialised epithelial cells
- Hepatic portal vein: O2 poor but nutrient-rich blood from GI. It passes to the liver for filtration before returning to the systemic circulation.

2-
- Hepatic veins (which drain into inferior vena cava): return deoxygenated blood to the systemic circulation

Question 6

What is the portal triad?

Answer 6

• Hepatic portal vein and Hepatic artery proper enter the liver
• Bile duct leaves the liver
  > Via Porta Hepatice

Question 7

What are the 2 locations of the portal triad?

Answer 7

1- The porta hepatis
2- Within the substance of the liver itself

Question 8

Liver makes Bile and is therefore a gland.
How is bile drained from the liver?

Answer 8

1- Bile is formed in the liver by hepatocytes
2- Travels through R+L hepatic ducts join at hilum of liver (Porta hepatis)
3- Common hepatic duct
4- Cystic duct ( Spiral valve - 2 way pathway)
5- Gal bladder
6- Cystic duct
7- Bile duct

Question 9

1- Where is bile stored? What is bile needed for?
2- What causes bile to be excreted?

Answer 9

1- Gal bladder > Fat absorption.
2- Excreted from the gallbladder into the duodenum in response to appropriate hormonal stimulation

Question 10

What kind of cells are hepatocytes? What are their 2 functions?

Answer 10

• Absorptive epithelial cells
  > Filter blood + Produce bile

Question 11

How are hepatocytes arranged? What lies between each plate of hepatocytes?

Answer 11

• Plates or cords of cells, with their absortive surfaces facing away from adjacent hepatocytes
  > Between each plate of hepatocytes are sinusoids =

Question 12

What are sinusoids?

Answer 12

Specialised vessels formed by a fenestrated endothelium, which means they have holes in them, and a discontinuous basement membrane.

> Allow substances to easily pass out of the blood and to come into close contact with the hepatocytes.

Question 13

What vessels do sinusoids receive blood from? What does this cause?

Answer 13

• Branches of both the hepatic portal vein and the hepatic artery proper.
  = Mixed blood is formed.

> > Substances from this mixed blood in the sinusoids are then able to pass through the holes in the fenestrated endothelium to enter an area called the space of Disse.
- This space is in close proximity to the absorptive surface of the hepatocytes

Question 14

What feature do hepatocytes have to maximise absorption?

Answer 14

• The surface of the hepatocytes is rich with microvilli to maximise surface area for absorption.

Question 15

Once bile is made by hepatocytes, where does it enter?

Answer 15

• Bile produced on basal surface of hepatocytes leaves the cell to enter a space called the bile canaliculus, or canaliculi for plural.
  > The bile in the canaliculi drains into the left + right hepatic ducts which combine to form the common bile duct.

Question 16

What happens to blood in the sinusoid as it moves through hepatocytes? Where does this blood then drain into?

Answer 16

• The mixed blood becomes increasingly more venous.
• It then drains into the central vein and towards the portal triad which ultimately passes into one of three hepatic veins.
• These veins then drain into the inferior vena cava allowing the filtered and deoxygenated blood to re-enter the systemic circulation.

Question 17

What is the structure of sinusoidal capillaries?

Answer 17

• Large intercellular gaps that allow free movement of proteins and cells across the endothelial lining - allowing for effective transport between blood and hepatocytes via the Space of Disse.

> High Kf

Question 18

What are the 2 additional cells found in the liver? What is their functions?

Answer 18

Stellate cell
Contain lipid droplets for vitamin A storage
Production of ECM and collagen when activated

Kupffer cell
Phagocytic
Remove spent erythrocytes
- reticuloendothelial system

Question 19

How are the plates of hepatocytes arranged?

Answer 19

• Radial manner to form Hepatic lobules
  > These polygonal shapes are bordered by a ring of portal triads, are bound by connective tissue and contain a single central vein (that receives venous, filtered blood)

Question 20

What does this histological slide represent?

Answer 20

Central vein of a single hepatic lobule
> Projecting out from the central vein are the sinusoids which in life would contain the mixed hepatic artery and hepatic portal vein blood.

Question 21

Label the histological slide of the portal areas.
Where would this collection of structures be found?

Answer 21

• At each corner of the hepatic lobule, with smaller branches running along the boundary between lobules to supply sinusoids running towards the central vein.

Question 22

What is Liver Acini?

Answer 22

• Functional unit of Liver
  > Crosses over two adjacent lobules, in a diamond shape with its apices at the two central veins of the two contributing lobules.

Question 23

What are the 3 zones of an Acini?

Answer 23

• An acinus is divided into 3 zones based upon the distance from the portal triad branches
• Zone 1 receives blood with the highest concentration of oxygen, but also the highest concentration of toxins absorbed by the gut
• Blood then flows through the sinusoid into zone 2 and ultimately zone 3.
• Zone 3 blood therefore has a low oxygen concentration but also a lower proportion of toxins

Question 24

1- Which zone does toxic damage mainly occur in?
2- Which zone does ischaemic damage mainly occur in?

Answer 24

1- Zone 1
2- Zone 3

Question 25

Compare how hepatocyte plates are organised structurally and functionally.

Answer 25

- Structurally via lobules - Functionally via acini

Question 26

What does this image show?

Answer 26

-Hepatocytes arranged into plates with the sinusoids lined by endothelial cells in between adjacent hepatocytes. - R = red blood cells (dark colour because very electron-dense) - H = hepatocytes - E = endothelial cells - D = space of Disse. Its between the endothelial cells and the hepatocytes - S = sinusoids - L = lipid - M = mitochondria - B = bile canaliculi (minute gaps between hepatocytes)

Question 27

What happens to hepatocytes when you ingest high concentrations of toxins ie alcohol, drugs?

Answer 27

1. Alcohol/drugs pass into the blood leaving the gut. 2. The liver then receives this blood via the hepatic portal vein. 3. This blood mixes with the oxygenated blood from the hepatic artery to run through the sinusoids of the hepatic lobules. 4. This **exposes the hepatocytes in close proximity to the sinusoids** to high levels of the toxins and therefore damages them and ultimately **kills** these cells 5. The **gaps left** by the **dead hepatocytes** cause the sinusoid to become full of twists and turns

Question 28

What happens to stellate cells when you ingest high concentrations of toxins ie alcohol, drugs?

Answer 28

- Stellate cells become **myofibroblasts which produce connective tissue** causing scarring of the liver

Question 29

What do the combined effects of the damaged hepatocytes and stellate cells ultimately cause?

Answer 29

- **Portal hypertension** by making it harder for the blood to pass through the sinusoid - = this **increases pressure within the portal venous system** (because the hepatic portal vein is 1 of the 2 blood vessels feeding into the sinuisoids) - = this makes it harder for venous blood returning from the gut to pass through the liver and back into the inferior vena cava - The tributaries of the hepatic portal vein **(splenic vein, superior mesenteric vein and inferior mesenteric vein)** therefore also become pressurised.

Question 30

There are 4 sites where venous drainage to the hepatic portal system and venous drainage directly in to the inferior Vena Cava overlap. What are they? And what does portal hypertension in these areas cause?

Answer 30

- **around the umbilicus** - **inferior part of the oesophagus** - **ano-rectal junction** - within the walls of the ascending and descending colon. > Pressure at these sites increases and some blood that would normally pass through the hepatic portal system flows instead **directly into the tributaries of the Inferior Vena Cava, thus bypassing the liver**. This abnormal blood flow **stretches the small vessels at these sites of anastomosis and produces clinical symptoms.**

Question 31

What are the clinical symptoms produced by portal hypertension at these 4 sites?

Answer 31

Sites of porto-systemic anastomoses portal hypotension causes: - Oesophgeal varices - Ani-rectal varices - Caput medusae (umbilicus)

Question 32

Why can failure of the liver to filter blood cause serious effects all over the body?

Answer 32

- Because the liver has a huge amount of functions which cause knock-on downstream effects all over the body

Question 33

Name some signs of liver pathology? - What is the classic presentation of pitting oedema?

Answer 33

- The skin does not bounce back when pressed.