Patterns In Liver Diseaase Module 4

Front 1

describe the liver structure of the hepatic lobule

Back 1

Front 2

what percentage of the blood supply enters the liver through the portal vein and hepatic artery

Back 2

- 60-70 % via portal vein

- 30-40% via hepatic artery

Front 3

describe how blood passes through the liver

Back 3

1. it enters through the hepatic artery, bile duct or portal vein

2. passes through acinar zone / periportal (closest to afferent blood supply)

3. passes through acinar zone 2/ midzonal

4. passes through zone 3/centrilobular

5. leaves via the terminal hepatic vein to the caudal vena cava

Front 4

what defences does the liver have

Back 4

- skin

- rib cage

- Kupffer cells

Front 5

what are Kupffer cells

Back 5

- fixed macrophages in sinusoid lumen on endothelial cell surface

- important in endotoxin removal from portal blood

Front 6

what defences does the biliary tree have

Back 6

- mucosal secretion - IgA from gastrointestinal plasma cells

- terminal sphincter in front of common bile duct that stops parasites/bacteria passing down into liver

Front 7

what problems can affect the portals of entry to the liver

Back 7

1. direct extension due to penetrating trauma

2. haematogenous entry of parasites/bacteria which ends up in the sinusoid and causes Kupffer cell localisation

3. retrograde biliary transport (going backwards) which creates ascending parasitic or bacterial infectious gain access

Front 8

give an example of liver damage in bovines

Back 8

bovine traumatic reticuloperitonitis with abscessation due to liver damge by eg small wires or nails causing direct extension from GIT

Front 9

how do poisonous plants like ragwort cause liver damage

Back 9

they contain alkaloids which are converted to pyrrolic esters by cytochrome P450 enzymes

Front 10

which species are mmost susceptible to ragwort toxicity

Back 10

pigs>cattle/horses> sheep

Front 11

what would a cell with ragwort toxicity look like histologically

Back 11

- presence of megalocytes (massive hepatocytes) due to remaining hepatocytes trying to replace those lost by necrosis

Front 12

describe how liver abscesses are formed in cattle

Back 12

caused by grain overload, rumen overload or carbohydrate engorgement

leads to lactic acidosis

leads to ruminitis -bacteria accumulate and pass to the portal vein

this causes hepatocellular necrosis, hepatic abscesses and hepatitis

Front 13

how is the liver damaged in navel ill in calves

Back 13

1. bacterial contamination of navel at birth

2. infection tracks up umbilical cord

3. causes multiple hepatic abscesses

Front 14

what are the mechanisms of liver injury

Back 14

- metabolic bioactivation of chemicals - cytochrome P450 to reactive species

- stimulation of autoimmunity

- stimulation of apoptosis

- disruption of calcium homeostasis due to cell surface blebbing and lysis

- canalicular injury (bile travels in caniculae)

- mitochondrial injury

Front 15

what are the main targets of liver injury

Back 15

- epithelial cells - hepatocytes, biliary epithelium

Front 16

what cellular changes occur with sub-lethal/reversible injury

Back 16

- cell swelling - hydropic degeneration, steatosis/lipidosis

- cell atrophy (cell shrinkage)

Front 17

what cellular changes occur with lethal?irreversible injury

Back 17

- necrosis - stimulates an immune response

- apoptosis - doesnt stimulate any cell response

Front 18

what are the three patterns of hepatocellular degeneration and necrosis

Back 18

1.random

2. zonal

3. massive

Front 19

what cellular changes are seen with random neccrosis

Back 19

- multifocal necrosis

- single cell/small number of affected cells

- viruses, bacteria, protozoa

Front 20

what are the characteristics of zonal necrosis

Back 20

- produces an enlarged, rounded liver

- specific zones degenerate

- mainly in centrilobular zone

Front 21

what are the characteristics of massive necrosis

Back 21

- effects entire lobule of liver (but not whole liver) or contiguous lobules (lobules next to each other)

Front 22

where are random hepatocellular necrosis like herpesvirus most common

Back 22

neonates/foetuses since the cant thermoregulate

Front 23

how would a liver with canine infectious hepatitis (CAV1) appear

Back 23

Front 24

why does zonal necrosis most often occur in the centrilobular zone

Back 24

this area recieves the least oxygenated blood so is susceptible to hypoxia and has the greatest enzymatic activity which activate compounds to toxic forms

Front 25

what are possible causes of zonal necrosis

Back 25

severe anaemia, right siided heart failure, passive congestion of liver which causes hypoxia due to blood stasis

Front 26

what do hepatic circulatory disturbances cause

Back 26

passive venous congestion due to increased pressure in the hepatic veins and venules relative to the portal venules

Front 27

what are the possible causes of hepatic circulatory disturbances

Back 27

- congestive heart failure

- partial obstruction of larger hepatic veins or caudal vena cava

Front 28

hepatic circulatory disturbances can cause acute passive congestion what are the features of this

Back 28

sudden engorgement with blood which can then cause anaphylaxis, shock or euthanasia

Front 29

hepatic circulatory disturbances can cause chronic passive congestion, what are the features of this

Back 29

- red centrilobular zones of congestion with loss of hepatocytes due to necrosis

- pale swollen periportal hepatocytes with fatty degeneration

Front 30

what is massive necrosis

Back 30

necrosis of an entire lobule or neighbouring lobules

Front 31

what would a liver with massive necrosis look like

Back 31

early - slightly swollen, smooth surface, dark parenchyma

- histologically - areas of haemorrhage and connective tissue

late - liver small with wrinkled capsule

- histologically - collapsed lobule with stroma and collagen replacing hepatocytes

Front 32

give an example of massive necrosis

Back 32

leptospirosis

Front 33

disturbances to bile flow and icterus can cause hepatic injury, how would the liver normally appear

Back 33

signs of jaundice/icterus due to hyperbilirubinaemia

yellow/brown, green/brown

Front 34

what are the 5 stages of the normal metabolism and elimination of bilirubin

Back 34

1. breakdown of old red blood cells

2. extrahepatic bilirubin is bound to serum forming a bilirubin-albumin complex which is delivered to the liver

3. hepatocellular uptake

4. glucuronidation in the ER - products are water soluble and readily excreted in bile

5. gut bacteria deconjugate bilirubin and degrade it to the colourless urobilinogens whichh are excreted in urine and faeces

Front 35

how can the portals of entry to the biliary system be damaged

Back 35

by direct extension

by haematogenous entry of parasites from blood

by retrograde biliary transport which gives access to bacterial or parasitic infections

Front 36

what is cholangiohepatitis

Back 36

a disease starting in the biliary system and spreading to the liver parenchyma

Front 37

what can liver fluke cause

Back 37

chronic cholangitis

ectasis (dilation of a hollow organ)

stenosis (abnormal narrowing of a passage in the body)

Front 38

how does the liver respond to injury

Back 38

-regeneration - hepatocyte growth factors

- fibrosis

- biliary hyperplasia

Front 39

how can the pattern of fibrosis suggest the underlying cause of the liver damage

Back 39

- centrilobular fibrosis = chronic toxic change/chronic venous congestion

- periportal fibrosis = chronic inflammatory changes

Front 40

what is cirrhosis

Back 40

scarring/fibrosis of the liver due to long term liver damage with hyperplastic nodule formation

Front 41

what are the causes of cirrhosis

Back 41

- chronic toxicity

- inflammation

- bile duct obstruction

- right sided heart failure

- inherited metabolism disorders

- idiopathic

Front 42

how does cirrhosis lead to oedema

Back 42

1. causes decreased albumin production

2. leads to hypoproteinaemia

3.leads to decreased oncotic pressure

4. oedema