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1

Normal Liver Mass

1500g
Largest organ

2

Normal Portal Pressure

5 - 10 mm Hg
Low pressure

3

Hepatocytes - Do they all do the same thing?

No!!!!
They have functional heterogeneity

4

Liver's borders

Right 5th rib
Left 6th rib
Right 9th rib

Feel it below the 9th rib and it's HUGE!!!!!!

5

Contents of the portal vein

Collection of venous blood from spleen, splenic vein, SMA, IMA

6

Portal Hypertension

Obstruction to portal vein flow causing pressure to increase above 10mm Hg

7

Post-Hepatic Hypertension

Rarest kind of portal HTN

Congenital webs of the IVC

8

Intra-Hepatic Hypertension

Most common type of portal HTN

Cirrhosis
Other types of pathology

9

Pre-Hepatic Hypertension

Thrombosis blocking entry to the portal vein

10

How many lobes?

2!

11

Components of the liver

2 Lobes
Glisson's Capsule (smooth! IT IS SMOOTH!!)
Falciform Ligament

12

Real divisions of the liver

8 Segments
4 on the left, 4 on the right
Each has its own vascular and biliary pedacle

13

Two sources of blood for the liver

Celiac Trunk > Hepatic Artery > Left & Right Lobes
Splenic Vein + IMA + SMA > Portal Vein

14

Biliary Tree

Bile conducted from ducts inside into common hepatic duct which meets with cystic duct to join the GI tract

15

Lobule

One functional unit of hepatocytes.
Central vein in the center
Arterial flow at the periphery
No connective tissue divisions between lobules the way pigs do!!!

16

Central veins

Marked by venous endothelium

17

Portal tracts

Collagen tracts that carry 3 tubes:

Bile duct
Artery
Vein

Can fibrose in pathways leading to other portal tracts when inflammation fucks that shit up

18

Blood path through a lobule

Portal tracts at periphery
Contents flow through sinudoids in the periportal regions
Undergo hella changes
Enter central veins to go back to the heart.

19

Bile Cannaliculi

Collect bile, interanastomose and form the canal of herring, which drains into the individual bile ducts that drain into the hilum and the common bile duct.

20

Where do the progenitor (stem) cells in the liver live?

The Canal of Herring

21

Description of Lobule

Radiating Cords
Nicely organized
Once Cell Thick (so nicely bathed)

22

Central Veins

Anastomose into Hepatic Veins (R & L)
Exit to IVC

23

Portal Tract on Histo

Nothing but collagen, fibroblasts and triad of structures
Inflammatory

24

Bile Duct

Tube of cuboidal epithelium

25

Limiting Plate

The hepatocytes at the edge of the Portal Tract
Chronic Hepatitis - Lymphocytes and inflammatory cells can infiltrate this structure and cause fibrosis

26

Mixing of Portal Venous and Hepatic Arterial Blood

Hepatic artery branches give off small twigs which empty arterial (oxygenated) blood into the periportal sinusoids directly outside the portal tract connective tissue

27

Chronic Hepatitis

Ground Glass Inclusions
Lymphocytes and other inflammatory cells cross limiting plate

28

Space of Disse

Type III Collagen
Discontinuous Array

29

Least oxygenated hepatocytes

Right around the central vein
They die quickly because they receive the least-oxygenated blood

30

Lipofuscin Pigment

Phagolysosomes with "Wear & Tear" cell debris
Brown Pigment Junk

Appears in Heart, Liver, and Adrenal. Myocytes particularly.
See it first in the hepatocytes surrounding central veins

31

Areas from Portal Tract to Central Vein

Periportal
Midzonal
Centrilobular

Each is about 7 cells wide
~22 hepatocytes from portal tract to central vein

32

Periportal Area - Zone 1

Best oxygen
Oxygen tension is 65mm Hg
Area where chronic hepatitis is most active
Gluconeogenesis
Bile Salt Synthesis

33

Centrilobular Area - Zone 3

Oxygen tension is 35 mm Hg
Furthest from oxygen
Most vulnerable to shock/ischemia
Contains drug metabolizing enzymes
Cytochrome p450s
Area where alcohol is metabolized

34

Acinar Zones

Another interpretation of
Zone 1 - Best perfusion
Zone 2 - Midzonal
Zone 3 - Centrilobular

35

Zone 1

Chronic Hepatitis
NH3 Metabolism (OTC & CPS Enzymes

36

Midzonal - Zone 2

Protein Synthesis

37

Zone 3

Drug Metabolism
Ischemia/Shock
Glutamine Synthetase Enzyme

38

Pit Cell

Natural Killer Cell
Tumor Surveillance

Tumor cells from GI tract come back in portal vein
Pit cells KILL THOSE BITCHES

39

Kupffer Cell

Macrophages
Contain multiple pseudopodia
Lie in waiting along endothelial surfaces
Phagocytose microbes

40

Endothelial Cells

Contain fenestrae in the sieve plate
Allow smallecules to move from Sinusoids into the Space of Disse

41

Space of Disse

Contains scattered discontinuous Collagen III fibers
Contains Ito (Stellate) cells
No basement membrane
Low pressure system (Dependent on how tight or loose the endothelial cells are, or how tight or loose stellate cells are

42

Stellate (Ito) Cells

Chief fibrotic source for the liver
Stores vitamins
Lies in wait for liver damage
Releases collagen on damage
Have little triangular basophilic nuclei (like little hats) over a vacuole of Vitamin A (fat soluble)

43

Canal of Hering

Bile canalliculi narrow to tubes lined by single cuboidal epithelium as they approach the bile ducts.
Progenitor cells live in that part
They can differentiate into whatever types of cells you need!!

44

Overdose of Vitamin A

Hyperplasia in Space of Disse

45

Endothelin and NO

Released in order to modify tension of endothelial cells and stellate cells

46

Bile Pumps

There are different bile pumps in the canaliculi
Studying these will reveal new forms of jaundice

BSEP
FIC-1
OATP

47

BSEP

Bile Salt Exporter Pump
Inhibited if you have septic shock from LPS

48

FIC-1

Familial Intrahepatic Cholestasis-1
Causes of jaundice in the liver itself

49

OATP

Organic anion transport pump

50

Cholestasis

Impaired bile secretion

51

Jaundice

Sallow yellow skin
Icteric sclera

52

LFTs

Liver Function Tests
Total Protein
Albumin
Globulin
Bilirubin Total
Bilirubin Direct (conjugated)
Bilirubin Indirect (unconjugated)
AST
ALT
Alk Phos

53

Total Protein

6.7 - 8.6 g/dL

54

Albumin

3.5 - 5.5 g/dL

55

Globulin

2.0 - 3.5 g/dL

56

When a hepatocyte dies, what is released?

AST/ALT

57

Pressure on bile ducts and canaliculi?

Elevated Bilirubin/Direct bilirubin
Alk Phos goes up
GGT (gammaglutamyl transferase)
5'NT (5' nucleotidase)

58

Synthesis

Synthetic proteins
Total Protein
Albumin

59

Synthesized in hepatocytes

Clotting Factors (I - II - V - VII - IX)
Albumin
Complement Proteins

60

Largest grey thing on EM

Erythrocytes

61

How does the liver regenerate?

Like medusa

62

How often do hepatocytes divide?

Every 400 Days

63

How many times can a hepatocyte divide?

70 Times

64

Regeneration after injury

Cell Division (eg hepatitis)

65

Severe Loss of tissue - Regeneration

From progenitor cells! (eg fulminant hepatitis)

66

Cirrhosis

An example of ABNORMAL REGENERATION with abnormally thick liver-cell plates
Cords are no longer 1 cell thick, but 3 or 4 cells thick
Blood can't squeeze through!! THAT SUXXXX
Portal fibrosis

67

Embryonic origins of liver

Gut ectoderm

68

Septum transversum

Primitive diaphragm running horizontally
Gut from narrow tube growing into connective tissue plate

69

22 Days post-blastocyst

Foregut endoderm goes into septum transversum.
Vitelline veins go into sinusoids

70

26 days post-blastocyst

Cystic Bud
(Cystic duct & gall bladder)

71

7 - 8 weeks

Portal vein
Portal tract
Sinusoids
Liver cords (many cells thick)

72

9 - 10 weeks

Bile duct plates (BDP) develop
Differentiation of periportal hepatocytes to bile duct epithelium (bile duct plate)

73

23 weeks and later

Double-lined tube regresses, is remodeled, and disappears
One portion moves into the tract to become the intralobular bile duct
Some liver diseases affect this remodeling (Polycistic Liver Disease)