liver histology - medicine 3

1

M3 sem 1 case 7:

Liver Microstructure

COMMONWEALTH OF AUSTRALIA

Copyright Regulations 1969

WARNING

This material has been reproduced and communicated to you by or on behalf of Adelaide University pursuant to Part VB of the Copyright Act 1968 (the Act).

The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of

copyright protection under the Act.

Do not remove this notice.

Presenter:

Dr Julie Haynes, Anatomy & Pathology, room N127,

Medical School.

Phone: 8313 5769, email: [email protected]

J Haynes 2006 © Human liver has minimal CT & lobulation is indistinct.

M3 sem 1 case 7, Image 1 - Liver Lobulation

2

J Haynes 2006 ©

The micrograph shows that pig liver has more connective tissue than

human liver and shows the arrangement of hepatocytes into classical

lobules. All blood flowing from the edge of the lobule drains into the

central vein. Centrals veins sublobular veins hepatic veins inferior

vena cava.


The hexagonal classical liver lobule:

•hexagon plates of cells

•central vein with radiating strands of hepatocytes, separated by sinusoids.

•portal triads in ‘corners’ of hexagon; consist of hepatic artery, hepatic portal vein & bile duct

•Classical lobule based on blood drainage of the liver.

J Haynes 2006 ©


portal triad

3

Fawcett DW. Concise Histology, Chapman and Hall, New York, 1997

The classical lobule

- considers the drainage of blood


The liver acinus

(or functional unit)

- considers the

blood supply

hepatic acinus •Considers blood supply.

•diamond shaped,

zone 1 (perilobular)

•cells have have first access to oxygen and nutrients in the blood ;

zone 2 (mid zone)

•cells are less favoured;

zone 3 (centrilobular)

•cells are least favoured

Cells in zone 3 are most vulnerable to damage from hypoxia, poor perfusion and certain toxins (eg. alcohol) whereas cells in zone 1 are affected least.

Fawcett DW. Concise Histology, Chapman and Hall, New York, 1997


4

Blood flow in classical

lobule (blue)

•At portal triads, blood in

branches of hepatic portal

vein &hepatic artery enter

sinusoids.

•Flows to central veins that

empty into sublobular

veins, hepatic veins & then

inferior vena cava.

•Bile flow in classical

lobule (green)

•Canaliculi, small gaps

between hepatocytes,

drain bile to periphery of

lobules into the smallest

epithelial lined bile ducts at

the portal triads Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005


M3 sem 1 case 7, Image 7 - Liver

• In the medium power view of the liver (pig) identify D, E, & F. What

label is the closest to cells in zone 3 of the liver acinus?

F

D

E

E

5


In the high power view of the liver: From what adjoining structure(s) has the fluid

in H come? From what adjoining structure(s) has the fluid in I come? From what

adjoining structure(s) has the fluid in J come? From what adjoining structure(s)

has the fluid in K come?

H

H

H H

H

I

I

J

K

M3 sem 1 case 7, Image 9A - Liver

The HP micrograph shows sinusoids and hepatocytes. Sinusoids are wide tortuous blood channels that

allow maximum exchange between blood & hepatocytes. They are incompletely lined by endothelial cells

& phagocytic cells (Kupffer cells). Space of Disse (not seen in routine sections of normal liver) is present

between sinusoids and hepatocytes and is where the actual exchange between hepatocytes and blood

occurs. Bile canaliculi are also not shown in routine sections. Hepatocytes are large cells (compare size

with RBCs); vesicular nucleus indicates active protein production and patchy cytoplasmic staining (not

shown in this photo) is due to abundant glycogen. Lipid appears as round clear droplets in hepatocytes.

Kupffer

cell?

endothelial

cell

B

lipid

endothelial cell

6

M3 sem 1 case 7, Image 9B - Liver

The HP micrograph shows sinusoids and hepatocytes. Hepatocytes are large

cells (compare size with RBCs); vesicular nucleus indicates active protein

production and patchy cytoplasmic staining is due to abundant glycogen.

J Haynes 2006 ©

J Haynes 2006 ©

M3 sem 1 case 7, Image 9C - Liver Sinusoids

The HP view shows Kupffer cells stained bright pink.

7

M3 sem 1 case 7, Image 10 - Liver Sinusoids

The electron micrograph shows (1) Kupffer cell, lining a sinusoid &

(2) Ito cell in space of Disse

Kupffer cell Ito cell

sinusoid

microvilli of hepatocyte in space of Disse

Ross, MH, & Pawlina, W. Histology, 5 ed, Lippincott, Williams & Wilkins, Baltimore, 2006.

sinusoid

J Haynes 2006 ©

M3 sem 1 case 7, Image 11 – Bile Canaliculi

The high power micrograph shows bile canaliculi, stained by a special technique

to show alkaline phosphatase. Canaliculi are in between hepatocytes and the bile

in them drains to bile ducts at the periphery of the classical lobules.

8

The top LM drawing shows how the intercellular spaces connect together to form a drainage system that flows into the epithelial lined bile ducts in the portal triads.

The bottom EM drawing shows the ultrastructure of hepatocytes. Note the Space of Disse where exchange between hepatocytes and blood takes place and the small intercellular spaces, canaliculi, where bile is secreted.

sinusoid

Kupffer cell

endothelial cell

space of Disse

Ito cell

Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005

M3 sem 1 case 7, Image

12 – Bile Canaliculi

bile canaliculus


• The HP micrograph shows a portal triad. Identify the triad components A, B,

and C. What would be present in abundance in cell D but not cell E?

B

C C

A cell E

cell D

9

17

M3 sem 1 case 7, Image

14A – Hepatocyte

Structure and Function • many organelles

• much synthesis

• high energy requirements

• each cell has multiple

biochemical activities

• many enzymes in SER &

RER are part of metabolic

pathways

• e.g. alanine aminotransferase

(ALT) Catalyses transfer of

amino group from analine to

alpha-ketoglutamate, to form

pyruvate & glutamate.

18

M3 sem 1 case 7, Image 14B – Glycogen Storage

Carbohydrate storage in the

liver. Glycogen storage is

associated with the smooth

endoplasmic reticulum (SER).

When glucose is needed,

glycogen is degraded. In

several diseases, glycogen

degradation is depressed,

resulting in abnormal

intracellular accumulations of

glycogen.


10

19

M3 sem 1 case 7, Image 14C – Protein Production in

Hepatocytes

Proteins produced by hepatocytes

are synthesized in the RER,

modified and packaged in

Golgi complex, secreted by

exocytosis.

The impairment of protein

synthesis in liver diseases and

starvation leads to several

complications, since most of

these proteins are carriers,

important for the blood’s

osmotic pressure and for

coagulation – e.g. albumin,

fibrinogen, and prothrombin


M3 sem 1 case 7, Image 14D – Bile Acids Secretion

Mechanism of secretion of bile

acids.

About 90% of bile acids are

reabsorbed in the intestine and

transported to the liver to be

recycled.

The remaining 10% are

synthesized in the liver by the

conjugation of cholic acid with the

amino acids glycine and taurine.

This process occurs in the smooth

endoplasmic reticulum (SER).

Alkaline phosphatase is bound to

canaliculi membrane and is

cleaved by bile acids during

secretion. In bile obstruction AP

enters the blood.


11

21

M3 sem 1 case 7, Image 14E

– Bilirubin Secretion

Water-insoluble bilirubin from hemoglobin

degradation in macrophages is tightly

bound with albumin in transport in the

blood.

Glucuronyltransferase in the SER of

hepatocytes conjugates bilirubin with

glucuronic acid to form water-soluble

bilirubin glucuronide. It is then secreted

into canaliculi.

When bile secretion is blocked, the yellow

bilirubin or bilirubin glucuronide is not

excreted; it accumulates in the blood,

and jaundice results.

More common cause of jaundice is the

obstruction of bile flow as a result of

gallstones or tumours of the pancreas.


22


The diagram shows a different focus of functions for hepatocytes relating to their location in

the liver acinus. After eating, cells in zone I are the first to take up glucose and store it as

glycogen. They are also the first to release glucose back into the blood after fasting. Cells in

zone II and zone III have progressively less access to glucose and oxygen. Cells in zone III

have more enzymes associated with anaerobic activities (e.g. glycolysis).

M3 sem 1 case 7, Image 15 – Hepatocyte Function

12

M3 sem 1 case 7: Answers

• M3 sem 1 case 7, Image 7 Ans: D = central vein, E = sinusoids, F = hepatic portal

vein (branch). Label D is closest to cells in zone 3.

• M3 sem 1 case 7, Image 8 Ans: H: from hepatic artery and hepatic portal vein; I: from

canaliculi; J: from hepatic artery; K: from hepatic portal vein.

• M3 sem 1 case 7, Image 13 Ans: A = bile duct tributary ; B = branch of hepatic portal

vein; C = branch of hepatic artery. Cells D contain glycogen..

liver histology - medicine 3

Documents