Large Animal Medicine Liver 1

Front 1

What provides the venous blood flow to the liver?

Back 1

Goes from small intestine to liver via the portal vein

Front 2

What artery provides blood flow to the liver?

Back 2

Hepatic artery
-25% of cardiac output (massive supply to liver)

Front 3

The arterial and venous supply of the liver (hepatic a. and portal v.) converge into ___________, and exit into central veins

Back 3

Sinusoids

Front 4

What do central veins drain into?

Back 4

The hepatic vein, then into the caudal vena cava

Front 5

What animals do not have a gall bladder?

Back 5

Horses
Camelids

Front 6

Explain the flow of bile.

Back 6

Bile--> canaliculi & bile ducts ---> cystic duct and gall bladder ----> common bile duct--> SI

Front 7

What is enterohepatic cycling?

Back 7

Substance excreted in bile is resorbed from gut and re-circulates in portal blood to the liver, then re-excreted

Front 8

What 3 things naturally undergo enterohepatic cycling?

Back 8

Bile acids
Bilirubin
Urobilinogen

Front 9

What happens to bile acids when there's a biliary tract obstruction?

Back 9

Bile accumulates and then overflows into the blood stream

Front 10

What is an example of a drug that undergoes enterohepatic cycling?

Back 10

Clindamycin- can lead to fatal effects

Front 11

What is the function of Kupffer cells?

Back 11

Clear particulate matter, antigens, endotoxin, bacteria and aged RBCs

Front 12

What happens when there's Kupffer cell compromise?

Back 12

Allows antigen escape (endotoxins, bacteria) and ultimately IgM production---> high globulin

Front 13

How much of the liver's function must be lost before there are signs of insufficiency?

Back 13

75-80%
-excellent capacity for regeneration

Front 14

What is the significance of finding hyperproteinemia on the blood work of an animal who has liver failure?

Back 14

Probably a chronic disease bc increased globulins, meaning it's harder to treat, poorer prognosis

Front 15

What are the 6 functions of the liver?***********

Back 15

1) Carbohydrate metabolism
2) Protein metabolism
3) Fat metabolism
4) Urea synthesis
5) Bile acid synthesis
6) Detoxification

Front 16

What is the major storage site of glycogen?

Back 16

The liver
-liver also regulates blood glucose

Front 17

What are the 3 types of proteins metabolized by the liver?

Back 17

1) Binding proteins
-albumin, transferrin, ferritin, ceruloplasmin, haptoglobin
2) Synthesis of clotting factors and physiological inhibitors
-abnormal bleeding is sign of liver dz*
3) Lipoproteins

Front 18

What does the liver do with regards to fat metabolism? (2)

Back 18

1) Major site of FA and ketone synthesis
2) Major site of cholesterol synthesis and metabolism

Front 19

What will you see on a CBC of an animal has low cholesterol due to liver failure?

Back 19

Abnormal RBC morphology since cholesterol makes up membranes

Front 20

What cells produce NH3 (ammonia)?

Back 20

All cells undergoing active amino acid catabolism

Front 21

What happens to ammonia produced by cells that undergo active amino acid catabolism?

Back 21

Converted to water soluble urea for excretion by the liver

Front 22

How are ammonia and urea levels affected by liver disease?

Back 22

Decreaes BUN and increase blood NH3
-acute severe disease animal may have high blood ammonia or if chronic and severe you will also see very high ammonia levels

Front 23

What is the major fate of cholesterol metabolism?

Back 23

Used to synthesize bile acids

Front 24

What is the function of bile acids?

Back 24

Emulsify fat, absorption of fat soluble vitamins

Front 25

What happens to bile acids after entering the small intestine?

Back 25

Taken up by active transport in the terminal ileum via entero-hepatic circulation

Front 26

What does the liver detoxify from the system? (4)

Back 26

Bilirubin, urea, aromatic amino acids, drugs

Front 27

How does the liver detoxify drugs? How can this be used to diagnose liver failure?

Back 27

Converts them to water soluble metabolites for excretion
-intolerance can be an early sign of liver disease

Front 28

What are 2 types of information that bile acids provide that hepatic enzymes do not?

Back 28

1) hepatic enzymes don't tell about liver function, bile acid accumulation means liver can't do its job
2) Bile acids are very stable compounds

Front 29

True or false. Bile acid synthesis decreases when an animal is in liver failure.

Back 29

False!! Liver keeps making bile acid no matter how sick animal an animal is, important thing is whether or not the liver can take it back up again bc this takes healthy cells and biliary tract
-why get increased bile acids with liver disease

Front 30

What is bilirubin derived from?

Back 30

Hemoglobin (80%) and non-Hb hemoprotein

Front 31

Explain the process of heme metabolism.

Back 31

Heme--> biliverdin --> unconjugated bilirubin, UCB enters liver----> water soluble CB (glucuronyl transferase)

Front 32

What happens to conjugated bilirubin that is formed in the liver, in a healthy animal?

Back 32

CB excreted, but small amount enters blood

Front 33

What is total plasma bilirubin?

Back 33

Total plasma bilirubin: UCB + small amount of CB

Front 34

What happens to conjugated bilirubin once it enters the intestinal tract?

Back 34

Converted to urobilinogen in the bowel

Front 35

What happens to the urobilinogen produced in the bowel?

Back 35

-Some urobilinogen undergoes enterohepatic cycling
-Small amount enters the urine

Front 36

How can you determine if a bile duct is patent via urinalysis?

Back 36

small amounts of urobilinogen in the urine indicate a patent bile duct

Front 37

What color is heme? biliverdin? unconjugated bilirubin?

Back 37

Heme= red
Biliverdin= green
Unconjugated bilirubin= yellow

Front 38

Hyperbilirubinemia can result from an increase in _____ or _____.

Back 38

Unconjugated bilirubin or conjugated bilirubin

Front 39

What are 3 causes of increased unconjugated bilirubin?

Back 39

1) Excess production (hemolysis)
2) Decreased uptake into hepatocytes
3) Disturbed intracellular protein binding or conjugation

Front 40

What are 2 causes of increased conjugated bilirubin (regurgitation into blood)?

Back 40

1) disturbed secretion of CB into canaliculi
2) Intra or extra hepatic bile obstruction
-think: my liver can take up bilirubin and convert it but can't excrete it think about intra or extrahepatic bile duct obstruction

Front 41

What are 4 things that are important components of history in an animal with liver failure?

Back 41

1) Vaccination or transfusion w/ blood or plasma?
2) Potential exposure to plant or chemical toxins
3) History of fever, colic or weight loss
4) Number of affected or exposed animals

Front 42

How do animals tend to present for clinically low grade liver failure?

Back 42

intermittent fever or low grade intermittent colic

Front 43

What do you normally find on physical exam of a large animal with liver failure?

Back 43

-Often not forthcoming
-mild injury often reflected only in biochemical profile
-clinicopathologic testing & diagnostic procedures are very important

Front 44

True or false. There is only a small chunk of liver that can be identified on a physical exam.

Back 44

True, lung covers majority of liver

Front 45

When do clinical signs of liver failure develop?

Back 45

When >75% of liver parenchyma is compromised
-hepatic disease without insufficiency causes few signs

Front 46

What are the pathognomonic signs of liver failure?

Back 46

There are none, sigs of liver failure are multiple and varied

Front 47

What are 3 clinical signs that are very suggestive of liver failure?

Back 47

1) Icterus
2) Hepatic encephalopathy
3) Photosensitization

Front 48

If you have a jaundiced foal what should be on the top of you differentials?

Back 48

Most likely neonatal isoerythrolysis
-very high bilirubin in these foals

Front 49

Icterus is a prominent feature of ______ in horses.

Back 49

Anorexia

Front 50

Icterus is more prominent in animal with elevated_________.

Back 50

Elevated Conjugated bilirubin

Front 51

What is hepatic encephalopathy?

Back 51

CNS dysfunction from hepatic failure

Front 52

What are some signs of hepatic encephalopathy in large animals?

Back 52

Depression, head pressing, walking, circling, ataxia, yawning

Front 53

What are 3 possible causes of hepatic encephalopathy?

Back 53

1) High ammonia
2) Altered CNS neurotransmitter
-Decreased branched chain AAs
-Increased aromatic AAs
3) Severe hypoglycemia may also induce CNS signs

Front 54

What are some differentials for hepatic encephalopathy?

Back 54

-trauma
-Viral encephalomyelitis
-rabies
-leukoencephalomalacia
-brain abscess
-EPM
-blister beetle toxicity
-botulism
-heavy metal toxicity
-gut associated hyperammonemia

Front 55

What are 10 common signs of liver failure?

Back 55

1) Icterus
2) Hepatic encephalopathy
3) Weight loss
4) Colic
5) Depression and anorexia
6) Pruritus
7) Ventral edema/ ascites
8) Hemorrhage
9) Diarrhea
10) Photosensitization

Front 56

Is weight loss usually an acute or chronic sign of liver failure? Why do these animals get weight loss?

Back 56

Chronic- anorexia, altered metabolism

Front 57

Is colic usually a sign of acute or chronic liver failure?

Back 57

Subacute

Front 58

Why do animals with liver failure get colic?

Back 58

-hepatic swelling, biliary obstruction
-Gastric impaction

Front 59

Why do animals with liver failure get ventral edema/ ascites?

Back 59

-Hypoalbuminemia (uncommon in horses)
-Increased portal pressure from hepatic fibrosis

Front 60

What large animal tends to get ventral edema with liver failure?

Back 60

Cattle, horses maintain albumin production well with liver disease

Front 61

Why do animals with liver failure hemorrhage?

Back 61

Impaired factor production (Clotting factors) and vitamin K absorption

Front 62

Which large animal tends to get diarrhea the most often with liver failure?

Back 62

Cattle

Front 63

Why do animals with liver failure get pruritus?

Back 63

Bile acids in skin

Front 64

Why do animals with liver failure tend to get diarrhea?

Back 64

Portal hypertension + increased hydrostatic pressure

Front 65

Does photosensitization tend to occur in animals with acute or chronic liver disease?

Back 65

Chronic disease

Front 66

What are the clinical signs of photosensitization?

Back 66

Erythema and crusting of non-pigmented skin

Front 67

Why do animals with liver failure get photosensitization?

Back 67

Liver can't metabolize chlorophyll so then phyloerythrin accumulates and it reacts with light

Front 68

True or false. Photosensitization means an animal has liver failure.

Back 68

False, plant toxins can cause photosensitization as well

Front 69

True or false. It's normal for large animals to have a small amount of bilirubinuria.

Back 69

FALSE, normal in small animals, but large animals should not have bilirubinuria bc goats, sheep, cattle have very low bilirubin levels and rumen microbes use up lots of bilirubin
- so bilirubinuria w/ no hemolysis= significant liver disease

Front 70

What should you do if an animal has bilirubinuria?

Back 70

Look for evidence of hemolysis, if no evidence of hemolysis then this is very indicative of liver disease

Front 71

What are the 2 types of hepatic enzymes?

Back 71

1) Hepatocellular (leakage) enzymes
2) Cholestatic enzymes

Front 72

Do you expect hepatocellular or cholestatic enzymes to increase more rapidly?

Back 72

Hepatocellular

Front 73

Often there is a mixture of leakage and cholestatic enzymes with liver failure, so how can you determine what the cause is?

Back 73

Usually is mixed, but usually one predominates and shows it's mainly biliary or leaking enzymes

Front 74

Why do leakage enzymes and cholestatic enzymes rarely occur as a single entity?

Back 74

-cellular damage results in cell swelling and secondary occlusion of the biliary tract
-biliary dysfunction causes retention of toxic bile products with secondary cellular damage

Front 75

What are 2 possibilities for why liver leakage enzymes go back to normal after an increase?

Back 75

1) Liver regenerates
2) Liver cells die

Front 76

Do hepatic enzymes reflect liver function?

Back 76

NO, hepatic enzymes are useful for detecting disease, but are not indicators of function

Front 77

An increase of hepatic enzymes reflects what 3 things?

Back 77

1) Leakage from damaged cells
2) Increases in enzyme secreting tissue
and/ or increased intracellular enzyme concentration

Front 78

What are the 4 leakage enzymes?

Back 78

1) ALT
2) AST
3) GLDH
4) SDH

Front 79

What increases the concentration of liver enzymes?

Back 79

Damage to hepatocytes

Front 80

True or false. There is a poor correlation b/w the degree of increase in leakage enzymes and to liver function.

Back 80

True, massive increases can occur with minimal functional deficits
-but generally speaking higher w/ more liver disease

Front 81

What does ALT stand for? Where is it found in large animals?

Back 81

Alanine aminotransferase
-liver has low concentrations

Front 82

What does AST stand for? Where in large animals is it found?

Back 82

Aspartate transaminase
Liver, muscle, red cells, kidney, brain

Front 83

How should you always interpret AST?

Back 83

May be indicative of liver or muscle disease so look at with CK and GGT
-CK is labile
-GGT lasts longer and increases with pretty much any liver issue

Front 84

When do AST levels peak? When do they decrease?

Back 84

Peak at ~24 h after single insult
Decrease 2-3 d

Front 85

If a horse has normal AST is it likely that it has active hepatocellular damage? Why or why not?

Back 85

NO, because AST is very sensitive and increases with even minor insults to liver

Front 86

What is the best indicator for hepatocellular damage in ruminants?

Back 86

GLDH- a mitochondrial enzyme

Front 87

When do GLDH levels peak after a single insult?

Back 87

~24 h

Front 88

What is difficult about measuring GLDH?

Back 88

Short half life and very labile

Front 89

When is sorbitol dehydrogenase release?

Back 89

Specific to hepatocellular damage
-Also increases occur w/ horses with acute GI obstruction or enteritis in horses

Front 90

When are SDH levels helpful?

Back 90

during acute disease, values normalize really quickly because short T1/2

Front 91

What causes SDH increase?

Back 91

Specific for hepatocellular damage

Front 92

Why is SDH rarely measured?

Back 92

Very labile, can only tell you if liver disease is active and ongoing or if normal then either issue resolved or cells have died

Front 93

What 2 enzymes are indicative of active biliary tract disease?

Back 93

ALP & GGT

Front 94

What causes increased induced enzymes (ALP & GGT)?

Back 94

increased de novo synthesis
-drugs: corticosteroids, barbiturates
-cholestasis

Front 95

Where in the body is alkaline phosphatase (ALP) found?

Back 95

Liver, GI, bone isoenzyme

Front 96

When do ALP levels peak?

Back 96

~5-6 days post insult

Front 97

What can cause massive increases in ALP?

Back 97

Bile duct obstruction

Front 98

Is ALP useful in large animals?

Back 98

Useful in horses, but not ruminants due to wide fluctuations in normal animals
-helpful to diagnose rickets in ruminants

Front 99

You have a young animal with a very high ALP and it stiff and doesn't want to move much and doesn't get much sun, what's the most likely diagnosis?

Back 99

Rickets

Front 100

ALP levels are normally high in ________.

Back 100

Neonates

Front 101

When do gamma glutamyltransferase (GGT) levels peak after due to cholestasis? How long does it last?

Back 101

~7 days
-long half life so takes months to decrease

Front 102

Renal GGT is contained within the ______.

Back 102

Urine

Front 103

What are 2 causes of increased GGT?

Back 103

1) Biliary duct obstruction
2) Biliary hyperplasia
-rapid increase in GGT even if primary hepatocellular damage

Front 104

It is very rare for _____ to have normal GGT with liver disease.

Back 104

Horses
-increased GGT w/ right dorsal displacement of the large colon due to bile duct compression
-higher if biliary tract disease

Front 105

GGT is a useful indicator of _____ and ________ in ruminants.

Back 105

liver disease
passive transfer

Front 106

Is it normal for a 1 1/2 week old foal to have a high GGT level? Why or why not?

Back 106

Yes, high for first 2 weeks of life from colostrum
-GGT can be 2-3 x normal

Front 107

What are the 4 non-specific function tests of the liver?

Back 107

1) Bilirubinemia
2) Total protein
3) Urinalysis
4) BUN

Front 108

What are 3 causes of bilirubinemia?

Back 108

1) Fasting
2) Hemolysis
3) Liver failure (not sensitive)

Front 109

What 2 types of liver failure causes bilirubinemia? What type of bilirubin increases with each?

Back 109

1) Early hepatic disease
-Initially increases in UCB
2) Obstructive biliary disease
-Intra or extra-hepatic, early on CB rises
-later on bile retention causes damage, decreased conjugation

Front 110

Bilirubinemia is not a sensitive indicator of liver failure in __________.

Back 110

Ruminants

Front 111

Animals with liver failure can get hypoalbuminemia as reflected by their total protein, but is rare in _______.

Back 111

Horses

Front 112

What will you see on urinalysis of an animal with obstructive biliary disease? When is it most prominent?

Back 112

CB renally excreted
-bilirubinuria prominent in extra-hepatic obstruction

Front 113

When is bilirubinuria highly suggestive of liver failure?

Back 113

In horses

Front 114

When is there increased urobilinogen in the urine?

Back 114

In hemolytic and hepatocellular patterns of icterus
-Not very stable and must be assayed in 1-2 h

Front 115

If an animal has profound bilirubinuria and a lack of urobilinogen, what is this highly suggestive of?

Back 115

Suggests significant bile duct obstruction

Front 116

What are BUN levels like in an animal with liver failure? Why?

Back 116

Decreased BUN due to altered production
-usually w/ severe or acute hepatic failure

Front 117

What normally happens to serum bile acids? What does increased serum bile acid reflect?

Back 117

Normally 95% resorbed from ileum into portal vein and extracted by liver
-Serum increases reflect reduced blood flow or extraction and/or regurgitation into circulation

Front 118

What is the level of serum bile acids that is sensitive for liver disease in horses? Cattle?

Back 118

Horses: > 20 umol/L
-single sample adequate
-increases w/ 3 days of fasting
Cattle: less helpful bc have higher serum bile acids, but great increase signifies liver not working properly

Front 119

What causes the greatest increase in serum bile acids?

Back 119

Portal shunt and cholestasis

Front 120

What does an increase in blood ammonia usually indicate?

Back 120

Diffuse disease or hepatic shunts
-may be normal in patients that have lost up to 60% of hepatic function in other diseases

Front 121

What is the downfall of measuring blood ammonia?

Back 121

Unstable
-ice or fridge samples, analyze w/in 6 hours

Front 122

**What are the landmarks for ultrasonography of the liver on the right and left side of a horse?

Back 122

1) R side: 6th to 15th ICS ventral to the lung
-hard to image on right side in old horses and horses w/ decreased hepatic mass
-horses= T18
2) Left side: 7th to 9th ICS ventral to lung
-does not change w/ age

Front 123

Where do you ultrasound the liver in cattle? Where is the gallbladder?

Back 123

Right side from 8th to 12th ICS
-rumen prevents visualization on left side
-gallbladder: ventral border in 9th-12th ICS

Front 124

Where do you ultrasound the liver in sheep?

Back 124

7th-12th ICS on right side
-Goat and sheep= T13

Front 125

Where do you ultrasound the liver in goats? gallbladder?

Back 125

Liver: 7th to last rib on right side
Gallbladder: extends below ventral border

Front 126

What is the normal appearance of the liver on ultrasonography?

Back 126

-Uniform density
-sharp edges and does not extend beyond CCJ
-anechoic vessels visible
-normal biliary system not visualized-should not shadow

Front 127

Compare the echogenicity of the liver to the spleen and kidney.

Back 127

-less echogenic than spleen (L sidE)
-Hyperechoic to kidney (R side)

Front 128

What are 4 abnormal findings of the liver that can be detected on ultrasonography? What can cause each abnormality?

Back 128

1) Focal increase in echogenicity
-Chronic abscessation or neoplasia
2) Minimally echogenic lesios
-cysts, hematomas, early abscesses
3) Diffuse increase in echogenicity
-fibrosis, inflammation, fatty infiltration
4) Cholelithiasis
-distended bile ducts and hepatomegaly
-hyperechoic shadowing masses

Front 129

What is the benefit of performing an ultrasound guided percutaneous biopsy of the liver?

Back 129

Assists site selection and avoids vessels and other structures

Front 130

What should you do if a pre-biopsy clotting profile is abnormal (often are)?

Back 130

Address w/ fresh plasma pre-biopsy

Front 131

*Where do you take a percutaneous biopsy in a horse?

Back 131

Right 12th ICS
-Just above line from tuba coxa to point of olecranon
-Left only do w/ ultrasound

Front 132

Where do you take a percutaneous liver biopsy in cattle?

Back 132

20-30 cm to R of midline of the back in the area of percussion dullness in the 11th or 12th ICS

Front 133

Where do you take percutaneous liver biopsies in sheep and goats?

Back 133

Same as cattle: 20-30 cm to R of midline of the back in the area of percussion dullness in the 11th or 12th ICS
-or ultrasound or liver palpation via small incision behind the last rib

Front 134

What are the 4 steps to performing a percutaneous biopsy?

Back 134

1) Clip and prepare for sterile biopsy
2) Desensitize SQ, muscle and parietal pleura
3) Stab incision at the CRANIAL aspect of rib
4) Insert needle to contact diaphragm
-then a further 2-4 cm into liver
-use tru-cut or automatic biopsy gun
-move dorsally if no sample, no higher than a line from tuba to POS

Front 135

What do you do after taking the percutaneous liver biopsy?

Back 135

-culture FIRST sample (hopefully cleanest), put remaining cultures in formaline
-ensure sample is dark and sinks! means it is really liver

Front 136

How common are complications with liver biopsies? Why?

Back 136

Uncommon
-even though lung & bowel frequently hit
-clinical bleeding rare even with increases PT/PTT
-can obtain other organs or normal liver tissue in animals with focal disease

Front 137

Why would you do a laparoscopy for liver diagnostics? What side would you perform it on?

Back 137

Right side: some visualization and allows biopsy

Front 138

What is the purpose of performing a hepatobiliary scintigraphy?

Back 138

Evaluates function and biliary patency
-distinguish biliary obstruction from other causes of hyperbilirubinemia
-normal values established for horses

Front 139

When would you perform portovenography?

Back 139

In foals to identify shunts

Front 140

When would you perform an exploratory laparotomy, in terms of liver diagnostics?

Back 140

-For suspected portal shunts
-diagnosis of liver disease in cattle

Front 141

What is the purpose of doing a fecal examination in an animal with liver problems?

Back 141

Liver fluke eggs can be present in ruminants

Front 142

What are 7 poor prognostic indicators of liver disease in large animals?

Back 142

1) Albumin < 2.5 g/ dL in horses
2) Hyperglobulinemia
-often chronic liver dz
3) PT > 30% above normal
4) Very high GGT & ALP w/ normal or low SDH
-chronicity & loss of hepatic mass
5) Marked fibrosis
6) Hepatic encephalopathy or hemolytic crisis
-usually terminal signs
7) Serum bile acids > 50 umol/L
*review case on liver 1