L3: Liver Path

fx (5)

-processing dietary carbohydrates, lipids, amino acids, and vitamins

-metabolic balance

• lipid and glucose turnover, synthesis and storage

-synthesis and turnover of plasma proteins

• clotting factors, albumin, vitamin K, etc

-detoxification and biliary excretion of endogenous wastes and xenobiotics

-innate immunity

• Kupffer cell filtration, cytokine synthesis, and Pit cells

what is the functional unit of the liver?

-wedge shaped acinus or polyhedral lobule

summary:

zone 1 hepatocytes

-surrounded by blood with the highest concentration of O2, insulin, glucose, and AAs

-principal site of gluconeogenesis, protein synthesis, aerobic metabolism, urea, lipid and cholesterol metabolism

summary:

zone 3 hepatocytes

-furthest from blood inflow

-site of glycolysis, lipogenesis, and biotransformation due to ^ cytochrome p450 levels

term:

limiting plate

-area that separates the portal tract CT

note:

pig lobules

-delineated by fibrous tissues

-easy to visualize

what happens to defect hepatocytes in zone 2?

-can dissociate from cords if the adhesions are lost

blood flow:

portal v

-from forestomach/glandular stomach, intestines, spleen, pancreas

-rapid clearance of nutrients, xenobiotics, microorganisms

-blood flow to sinusoids

blood flow:

hepatic a

-oxygenated blood

-disperse into the peribiliary capillary plexus > sinusoids

summary:

hepatocytes

-arranged in single-cell plates/cords bordered with sinusoids

-sinusoids are lined with endothelial cells

-gap between the endothelial cells and hepatocytes – Space of Disse - usually not visible by light microscopy

-Kupffer cells – within the sinusoid

-Stellate cells – within space of Disse

summary:

sinusoids

-special fenestrated endothelium facilitates passage of fluids and particulates into the perisinusoidal space (Space of Disse)

-with damage, 'capillarization'/ loss of fenestrations interferes with uptake and secretion.

summary;

Kupffer cells

-fixed tissue macrophages within the sinusoidal lumens

-remove particulates, dead cells and bacteria-filtering organ

-cytokine and pro-inflammatory mediator secretion

summary:

pit cells

-large granular lymphocytes with NK cell activity in sinusoidal lumens

-innate immunity

summary:

ito cells/hepatic stellate cells

-within the perisinusoidal space

-secretes extracellular matrix of sinusoids

-inflammation causes extra secretion = capillarization + contractile element production restricting blood flow

-regulate microvascular tone and sinusoidal flow

-store lipid droplets rich in vitamin A

-notable aged carnivores

Kupffer cell

-visible from accumulated intracytoplasmic pigment (age or injury)

Ito cells

-perisinusoidal space

-ntracytoplasmic lipids (why they look like fat droplets)

blood flow:

central vv

sinusoidal blood flow → central vv → CaVC

flow:

lymphatic drainage

-perisinusoidal space → lymphatics (capsule & portal tracts) → hepatic nodes (hilus)

summary:

canaliculi

-intercellular space between 2 hepatocytes isolated by tight junctions

-secretes bile.

-difficult to recognise unless distended

summary:

biles ductules

-canaliculi connect to bile ductules via the canal of Hering (w/ oval cells)

-multiply with severe hepatic injury

-blood vessels

-bile duct

-hepatocyte

-oval cells

summary:

bile ducts

-cuboidal or low columnar epithelium

-modify bile composition and secrete substances

-recognisable as part of the portal triads

• hepatic artery, hepatic portal venule, and bile duct

fx:

gallbladder

-bile storage before release into the GIT

liver:

postmortem

-breaks down fast

-core site within body → kept at a higher temperature

-bacteria rapidly spread from the gut

-gas bubbles + bile imbibition in surrounding tissues

-bile imbibition

-gas bubbles

Which hepatocytes are most susceptible to direct-acting toxicants?

A. zone 1- Periportal

B. zone 2- Midzonal

C. zone 3- Periacinar/ centrilobular

C.

-receive the least amt of blood so can not handle more stress

-lots of P450 enzymes that metabolize toxins

Which hepatocytes are most susceptible to hypoxia and/ or indirect or metabolically activated toxicants?

A. zone 1- periportal

B. zone 2- midzonal

C. zone 3- periacinar/ centrolobular

C.

-least amt of oxygen so can will experience hypoxia first

developmental anomalies (2)

-cysts

-biliary atresia

summary:

cysts

-serous cysts: young animals, capsular, incidental

-biliary cysts

• associated with polycystic kidney disease in cats, Westies, and Swiss Freiberger horses

-serous cyst attached by a stalk to the hepatic capsule

(calf)

types:

congenital vascular anomalies

-congenital arteriovenous fistulae- dogs & cats

-portal vein hypoplasia- dogs

-portal microvascular dysplasia- dogs

-sequelae:

• portal hypertension & acquired extrahepatic shunts

congenital vascular anomalies

how?

-arteriolar proliferation and parenchymal fibrosis

-hepatic parenchyma atrophy (serum bile acids)

types:

portosystemic shunts

-congenital

-acquired

portosystemic shunts types:

congenital

-intrahepatic = patent foetal ductus venosu

• large breed dogs; Irish wolfhounds

-extrahepatic = portal vein/ tributory> vena cava or azygos vein

• small breed dogs (Yorkies, Maltese), cats

portosystemic shunts types:

acquired

-secondary to portal hypertension: post necrotic scarring

-thin wall, tortuous portal v/tributary → VC

K9

Congenital intrahepatic shunt, persistent patent ductus venosus

Congenital extrahepatic portocaval shunt in a dog

Multiple acquired portosystemic vascular shunts in a dog with chronic liver disease.