Ch 33 Hepatobililary

Question 1

Where does most cell regeneration occur in the liver?

Answer 1

Rappaport’s zone 1 (portal). Then cells are pushed to the central lobular area.

Question 2

At what point post product administration does acute serum hepatitis occur?

Answer 2

4-8 weeks

Question 3

Which clotting factors are produced by the liver?

Answer 3

Factors I, II, V, VII, IX, and X

Question 4

Briefly, what is the pathogenesis and common differential diagnoses for equine icterus?

Answer 4

Failure of uptake, conjugation, or excretion of bilirubin.
Massive hemolysis, bile blockage, equine fasting/anorexia

Question 5

Briefly, what is the pathogenesis and common differential diagnoses for bovine ascites?

Answer 5

Portal hypertension and lymph leakage via cirrhosis or veno-occlusion.
Cardiac failure, hypoproteinemia, cushing’s syndrome

Question 6

How do you diagnose hepatic encephalopathy?

Answer 6

1. Blood ammonia: liver isn’t metabolizing it to urea. But poor correlation
2. Clinical signs: neurologic, ruminants show tenesmus or vocalize. Horses develop central blindness or headpress, excitable
3. Possibly postmortem: increased CSF glutamine?

Question 7

Which are the hepatic ‘leakage enzymes’? What do they indicate, respectively?

Answer 7

AST, SDH, GLDH, LDH. Indicate hepatocellular injury or necrosis
1. Aspartate aminotransferase: From liver, muscle, erythrocytes, and heart.
2. Sorbitol dehydrogenase: Short t-1/2, acute dz indicator. Liver-specific. May elevate due to dehydration or hypoxia, not liver disease necessarily

3. Glutamate dehydrogenase: Liver-specific, not elevated in chronic dz
4. Lactate dehydrogenase: Not specific. Short 1-1/2. Also in erytrocytes

Question 8

What are the ‘cholestatic’ enzymes? What do they indicate?

Answer 8

GGT (gamma glutamyltransferase): Liver-specific. High in colostrum-drinking neonates. May elevate with colonic displacement due to bile duct compression.

ALP (Alkaline phosphatase): Liver, bone, intestine, macrophages, placenta. Nonspecific.

Both more likely to elevate in chronic disease. Associated with biliary obstruction

Question 9

What is the most sensitive indicator of liver disease in the horse?

Answer 9

GGT. Levels stay elevated for weeks

Question 10

What can serum urea nitrogen indicate in liver disease. How can it be misleading in cattle?

Answer 10

SUN/BUN: Liver produces urea, so if SUN drops, could indicate liver disease. HOWEVER, can also drop if a ruminant is off feed, because the bacteria are using it all to make protein

Question 11

What is the half life of albumin in the horse vs cattle and sheep?

Answer 11

Horse: 19.4 d
Cow: 16.5 d
Sheep: 14 d

Reduced in chronic liver disease

Question 12

What type of amino acid increases in liver disease?

Answer 12

Aromatics… short branched chain aa’s are decreased

Question 13

How can bilirubin indicate liver damage? What does it tell you?

Answer 13

-Incr bilirubin ddx: liver failure, bile blockage, hemolysis, or fasting (horse).

-In horse/cattle, rising bilirubin = retained unconjugated BIL. The direct(conjugated) to Tbil ratio can also rise in liver disease.
-Bile blockage/intrahepatic cholestasis increases Direct: total ratio
-Increased DIRECT(conjugated) bil usually due to hemolysis
-Blocked bile ducts will increase the conjugated AND unconjugated bil
-Equine TBil increases with fasting due to reduced removal.
-Normal ruminant Tbil is low
-

Question 14

Which is the most sensitive indicator for liver function?

Answer 14

Bile acids. In horses, > 20 umol/L is specific for nonsurvival.
Cattle have much higher ranges

Question 15

What indicators would spell a poor prognosis in liver disease?

Answer 15

-Albumin < 2.5 or incr. globulin
-Prothrombin time > 30% normal
-Greatly elevated GGT, ALP, with normal or decreased SDH or LDH.
-Marked fibrosis
-Signs of hepatic encephalopathy

Question 16

Where are liver biopsies collected in the horse?

Answer 16

Horse: R 14th IC space, at intersection of tuber coxae to point of shoulder. Needle directed slightly cranial-ventral, with US guidance

Cow: 11th right ICS intersected with horizontal line from PL fossa

Question 17

How is idiopathic acute hepatitis/Theiler’s disease, diagnosed in horses?

Answer 17

Bloods: high UC or total bilirubin, high bile acids and hepatocellular & cholestatic enzymes. Low BUN, hyperammonemia, prolonged clotting time, decr albumin

PCR for serum or liver Equine parvovirus-hepatits

Biopsy: Centrilobular & midzonal necrosis. Pale, eosinophilic granular mass outlining necrotic hepatocytes.

Question 18

What causes infectious necrotic hepatitis/black disease? How does it cause disease?

Answer 18

-Clostridium novyi type B. Exotoxins alpha and beta
-Occurs when larval migration of liver flukes has created damage enough for an anaerobic environment
-Patho: Alpha toxin and beta toxin:
Alpha toxin inhibits guanosine triphosphatases by glycosylation
Beta toxin is a necrotizing lecithinase.

Enters animal by ingestion from soil, then disseminates into kupffer cells and whole macrophage system. Anaerobic conditions allow spores to vegetate and proliferate, release toxins –> coagulative necrosis, then exotoxins disseminate. Sudden death

Question 19

How is Black disease diagnosed?

Answer 19

Necropsy: areas of coagulative necrosis yellow-white, with hyperemic zones
+
Isolating C. novyi type B from the liver: culture, fluorescent antibody ID of impression smears, toxin ID
OR: gram stain an impression smear to find gram positive rods,

Question 20

What is the pathogenesis of bacillary hemoglobinuria?

Answer 20

Agent: Clostridium haemolyticum. Has a beta toxin, a phospholipase C causing hepatocyte necrosis, hemolysis, and damages capillary endothelium. Causes hepatic necrosis and intravascular hemolysis.
-Sudden death in cattle and livestock
-Assoc with fluke migration
-Ingested from soil, hangs out in macrophages, lives in kupfer cells for long time. Localized anaerobic liver area leads to spore germination, proliferation, toxin production, necrosis, and thrombus formation

Animals > 1 yr old.

Question 21

How do you diagnose bacillary hemoglobinuria?

Answer 21

Bloods: Incr hepatic enzymes and TBil. PCR for organism and toxin (cattle).
Urine: Hemoglobinuria.
Smears: blood, peritoneal fluid, liver, or spleen.
Necropsy: Fluorescent antibody tests on impression smears from a liver ‘infarct’.

Question 22

How should liver enzymes and indicators be interpreted in the neonatal foal?

Answer 22

-TBil is incr due to converting fetal hemoglobin to adult
-ALP incr due to osteoblasts
-GGT elevated for 2-4 weeks (but only slight in SDH).
-Serum bile acids incr for first 6 weeks

Question 23

What is Tyzzer’s disease, and what is its pathophysiology?

Answer 23

-Acute hepatitis of foals 7-42 d old
-Blame: Clostridium piliforme. Gram neg, flagellated, intracellular obligate anaerobe
-Isolates E and R1 usually in horses
-Die in 2-48 hours. Spontaneous or in outbreaks.
-Contributors (patho unknown): young dams, high protein diet to dams, crowded conditions,

Question 24

How would you diagnose Tyzzer’s?

Answer 24

-Cx: neuro, colic, found dead, fever.
-Overwhelming sepsis
-Incr bile acids, bili, liver enzymes,

*Necropsy: Acute, widespread multifocal necrosis and hepatitis. Filamentous bacteria at lesion periphery. Silver or giemsa stain.

Question 25

How might late-term infection with EHV-1 affect a weak but live-born foal?

Answer 25

-Severe, multifocal necrotizing hepatitis with inclusion bodies. -NOT elevated liver enzymes -General respiratory distress

Question 26

How are neonatal isoerythrolysis and liver failure related? What causes this and how can you reduce the risk?

Answer 26

-Multiple blood transfusions (esp if 4L+) can cause iron overload, and chronic hypoxia from NI can cause liver failure -Deferoxamine: iron chelator increases urinary iron clearance and prevents iron tox in healthy foals. Give 12hr prior to transfusion

Question 27

What is kernicterus? How does it develop?

Answer 27

Bilirubin encephalopathy. Can result from NI as well because unconjugated bilirubin is toxic to the CNS. -Esp if TBil > 27.

Question 28

How does iron toxicity occur in foals?

Answer 28

*Foals given iron before receiving colostrum! See Cx 2-5 d later: hepatic encephalopathy, icterus, elevated GGT, ALP, ammonia, TBil, PCV. Seizures, depression, ataxia. Small livers with prominent bile duct proliferation, hepatic cell necrosis, and changes in the brain

Question 29

What is the pathophysiology of pyrrolizidine alkaloid toxicity?

Answer 29

-Indirectly toxic; bioactivated via hepatic metabolism -Pyrroles crossling double-strand DNA, then an antimitotic effect. -Hepatocytes cannot divide so become megalocytes. When they die, they're replaced by fibrosis -Toxic effects seen when hepatonecrosis and fibrosis lead to loss of function Downstream effects: Fibrosis disrupts bloodflow, prevents regeneration and leads to portal hypertension. -Ruminants: see diarrhea and ascites, rectal prolapse, weight loss, tenesmus -Horses: neuro signs, weight loss, slight icterus.

Question 30

What are the clinical signs of fasciolosis in ruminants? What aspects of fluke infestation cause these?

Answer 30

Proliferative cholangiohepatitis Cattle 1. Nutritional stress: less fertile, longer calving interval, lightweight calves 2. Anemia: blood feeding flukes 3. Depression, anorexia, anemia, biliary hyperplasia: Proline, from fluke metabolism Sheep/goats: most damaged -Fatal ascites, abdominal hemorrhage, pallor, icterus: massive fluke entry into bile ducts 6-10 weeks post infection -Chronic: submandibular edema, ascites, emaciation

Question 31

How do you diagnose fluke infestation?

Answer 31

Fecal sedimentation High probability of losses indicated when >10 eggs per 2gram. *also elevated GGT, GDH, eosinophilia Eggs are amber, larger, and more rounded at the operculum than Paramphistomum eggs

Question 31

How do you diagnose PA toxicity?

Answer 31

Vague: Elev GGT and ALP. Bile acids >>> Inc bilirubin later. *Biopsy or necropsy shows: 1. Fibrosis 2. Bile duct proliferation 3. Megalocytosis

Question 32

Which organism is most commonly implicated in bovine hepatic abscesses, and what are the virulence factors?

Answer 32

Fusobacterium necrophorum: gram neg, pleomorphically rod-shaped anaerobe. (also in calph diphtheria, footrot) Normally inhabits the rumen, in higher conc in cattle fed more grain (starch). Virulence factors: MANY. But Leukotoxin is #1. Subspecies necrophorum produces more leukotoxin. Subspecies funduliforme produces less. Enters portal blood through damaged rumen (rumenitis), establishes infection in the liver. **THere's a vaccine targeting leukotoxin and outer membrane proteins!

Question 33

Which is the second most commonly isolated organism in bovine hepatic abscesses?

Answer 33

Trueperella pyogenes: gram pos rod. -Esp likes the ruminal wall -Facultative aerobe

Question 34

What, in brief, is the pathophysiology of bovine hepatic abscesses? How do bacterial virulence factors play a role in this?

Answer 34

1. Sudden change to high energy diet or other cause of rumenal acidosis or ingestion of damaging materials. 2. Damaged rumen wall is susceptible to colonization by F. necrophorum 3. F. necrophorum accesses blood, makes rumenal wall abscesses, and sheds bacterial emboli to portal circulation 4. Bacteria filtered by liver NOW THE VIRULENCE FACTORS 1. proteases, dermonecrotic agents, cytotoxic allows further rumen wall damage 2. Leukotoxin prevents phagocytosis 3. Release cytolytic products that damage liver 4. Makes itself an anaerobic environment by killing other cells

Question 35

What are the most commonly isolated bacteria in equine hepatic abscesses?

Answer 35

Strep equi, E coli, bacteriodes fragilis, etc

Question 36

What are the primary prepartum risk factors of hepatic lipidosis?

Answer 36

BCS > 4.0; severe feed restriction, excess feed energy, long calving intervals

Question 37

What are the postpartum risk factors of hepatic lipidosis?

Answer 37

Concurrent diseases, reduced DMI, sudden changes in feed

Question 38

What are the risk factors in does and ewes for pregnancy toxemia?

Answer 38

Ewes: 2 or more lambs Dose: 3 or more kids Both: last 2-4 weeks gestation, obese dam, poor quality feed, cold weather, lack of exercise, stress of movement during risk period, excessively thin does/ewes

Question 39

How do you diagnose pregnancy toxemia?

Answer 39

Ketones in urine before detected in blood. -Acidosis, low Calcium and potassium BHB > 1 mmol/L

Question 40

What are the primary causes of equine hyperlipidemia?

Answer 40

Overproduction of VLDL, especially the abnormal type VLDL1 with reduced apolipoprotein B100 and B48 content, which enables greater TG content Decreased caloric intake.

Question 41

How do you diagnose hyperlipemia?

Answer 41

Triglycerides in serum > 500 Opaque/fatty plasma , fatty liver and kidneys on necropsy

Question 42

What triad of clinical signs indicates equine cholelithiasis?

Answer 42

1. Recurrent colic 2. Intermittent pyrexia 3. Icterus

Question 43

Where are choleliths more likely to be seen on ultrasound?

Answer 43

The cranioventral right hepatic lobe, ICS 6-8 Also see dilated bile ducts