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pathophysiology of NEB in periparturient dairy cattle
- dairy cows have a NEB during transition period - drop in dry matter intake before parturition and increased energy demand in early lactation.
- Can't eat enough, so mobilize NEFAs form adipose. Liver can't export LDL very well so stores. Other pathway, Acetyl CoA goes to Krebs or becomes ketones.
- Excessive NEFA and ketones are normal in transition cows, excessive is the problem.
- inability to adapt to early lactation vs underfeeding
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Cut-points for blood BHB classification of hyperketonemia
- Mild hyperketonemia: ≥ 1.2mmol/L
- severe hyperketonemia: ≥ 3.0 mmol/L
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Treatments for hyperketonemia (>1.2, >3), hepatic lipidosis, nervous ketosis
- subclinical (BHB ≥ 1.2 mmol/L): propylene glycol SID PO (glc precursor and reduces insulin sensitivity) via oral drench, Vitamin B12 (more krebs = less ketones). NOT STEROIDS
- clinical (BHB ≥ 3.0 mmol/L): dextrose 0.5-1 bottle IV, propylene glycol, Vitamin B12, NOT STEROIDS
- hepatic lipidosis: repeated 1/2 bottles of dextrose BID PRN, may take days, Propylene glycol, vitamin B12, NOT STEROIDS
- nervous ketosisIV dextrose, propylene glycol, B12
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Sequelae associated with liver abscess formation
- caudal vena cava thrombosis syndrome (CVCT): extension of abscesses into caudal vena cava, phlebitis and thrombus formation. can obstruct blood flow to heart, or cause pulmonary emboli (lung abscesses), cardiac infarction, endocarditis.
- weight loss, increased resp effort, necrotic breath, hemoptysis and/or epistaxis, death, vagal syndrome, chronic diarrhea/ascites (rare)
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bacterial causes of disease associated with liver fluke migration (2)
- bacillary hemoglobinuria/redwater: clostridium novyi type D. spores in soil, germinate in liver. Flukes cause necrotic anaerobic environment, toxins cause hepatic necrosis and intravascular hemolysis. (death or almost death, thin blood and hemoglobinuria, pale icteric mm)
- Black Disease: infectious necrotic hepatitis, clostridium novyi type B. Death but normal urine and rapid putrefaction of of tissues.
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sheep copper needs, normal food and molybdenum ratio
- need 4-6ppm copper to avoid deficiency
- normal is 8-11 ppm (but this could even be toxic)
- Molybdenum is a copper antagonist, lowers levels. Sulfates also decrease copper accumulation
- Cu:Mo = 6:1 or 10:1
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Places ruminants might get too much copper
- minerals and foods for swine, cattle, horses, chickens, rabbits, even meat or show goats. Milk replacer.
- soybean meal and corn distiller grain
- swine or poultry manure spread on grass, then eaten by sheep
- footbaths using copper sulfate or drinking water treated with copper to control algae or snails
- copper oxide wire particles for haemonchus control
- diet too low in calcium, molybdenum, zinc or sulfate
- liver damage duet o eating pyrrolizidine alkaloids
- breed susceptibility: suffolk and texel better at absorbing minerals
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Copper poisoning pathogenesis
- sheep/goats/camelids fed too much copper, copper accumulates in liver. Stays even if STOP feeding copper.
- Stressful event causes release of lots of copper at once.
- hemolytic crisis (plasma copper increase 24-48h pre). Copper increases and glutathione decreases in RBC. Methemoglobinemia and heinz bodies. Splenic sequestration or intravascular hemolysis
- may be prehemolytic necrosis 6-8wks pre (LDH and AST increase)
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senecio
- plant that causes liver disease in ruminants, esp cattle.
- Liver cells can't divide, so can't replace.
- Increases copper storage
- enzootic icterus
- also heliotropium, echium. Pyrrolozidine alkaloids
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signs of leptospirosis
- differential for copper poisoning
- fever
- hemolytic anemia, hemoglobinuria
- icterus
- abortion
- tetracycline to treat
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copper storage in llamas
- from concentrate feeds
- not icteric
- no hemoglobinuria
- enlarged liver, hepatic necrosis.
- Need 5-10ppm dietary copper (sheep levels, NOT goat)
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clinical signs of copper poisoning (and necropsy)
- anorexia, lethargy, increased RR, icterus (muddy from metHb), coffee-colored urine, arched back from kidney pain
- maybe petechial hemorrhages and photosensitization (edema and necrosis), or bloody urine, tubular necrosis and high liver copper without icterus.
- Necropsy: yellow mm and fat, dark grey kidneys, spongy brain deterioration, necrosis in liver. Submit liver and kidney, liver may have release ALL copper.
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copper poisoning ddx
- Lepto! Oxytet, but think copper first
- Haemonchus!
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Treatment for copper poisoning
- IV fluids to flush
- Blood transfusion PRN
- methylene blue to convert methemoglobin back to hemoglobin (long withdrawal). OR penicillamine, oral ammonium molybdate plus sodium sulfate or gypsum. ammondium tetrathiomolybdate
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3 causes of liver abscesses in small ruminants
- listerial hepatitis: neonates, miliary lesions. Stop feeding contaminated food.
- omphalophlebitis: dip navels, clean lambing pen
- caseous lymphadenitis: corynebacterium pseudotuberculosis: liver or lung abscesses in adults, weight loss, maybe external lymph node abscesses in herd
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fasciola hepatica
- from aquatic snails, rare in NY.
- Acute fluke disease = peritonitis from migration of flukes vs chronic disease from fibrosis in bile ducts.
- hypoproteinemia, anemia.
- Keep OUT OF WATER
- eggs don't float on a fecal, black trails of feces in liver.
- albendazole and clorsulon kill flukes, high dose closulon kills younger. IVERMECTIN WON'T
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Fascioloides magna
- deer fluke, sheep and goats abnormal hosts
- Huge, aimless wandering of 1-2 flukes can be fatal in 6 months
- Not patent in sheep and goats (no eggs)
- albendazole
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dicocoelium dendriticum
- terrestrial snails and ants/slime balls
- tiny flukes
- bile duct hypertrophy and eventual cirrhosis
- not very pathogenic (no migration)
- albendazole
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treatment of liver flukes
- Keep away from wet areas
- albendazole kills adults
- clorsulon at high doses kills juvenile (only in Ivomec Plus)
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Black disease
- clostridium novyi B
- 100% acute mortality
- spores already in liver, fluke migration makes necrotic, anoxic places for them to grow.
- Exotoxins cause rapid death.
- Infectious necrotic hepatitis
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side of horse to access liver
- right
- only 25% have access on L side (but that can be useful)
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Go-to enzyme for equine liver disease
- GGT (biliary injury, epithelium
- SDH and GLDH have too short of half-lives (good for tracking treatment progress, hepatocellular, AST too)
- ALP has no value in a horse
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LIver failure in equine
- RARE (disease is common)
- 60-70% hepatocyte loss.
- Liver disease that has progressed to loss of liver function
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Clinical signs of liver failure in horses
- mostly cortical, HEPATIC ENCEPHALOPATHY
- marked icterus
- discolored urine (shake, bubbles look green!)
- weight loss (in chronic)
- dermatitis
- colic
- lar par
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Tests for equine liver failure
- Bilirubin: direct/conj most specific because you don't see it without GB/liver failure, but both. 25% rule says >25% of bilirubin is conjugated, significant biliary obstruction is part of disease process
- Ammonia
- clotting times
- Bile acids: no need for pairs, constant secretion. >25 = liver prob. Prognostic indicator in CHRONIC
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Equine prognostic indicators in liver failure
- bile acid leel in CHRONIC liver disease of equines, only indicates disease in acute
- neuro signs (uncontrolled HE)
- U/S findings/liver biopsy
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causes of liver failure (7)
- obstructive/cholestatic
- acute hepatic necrosis (like Theiler's)
- toxic (plants)
- metabolic (HL)
- vascular
- chronic inflammatory/immune mediated
- neoplastic
- unknown/idiopathic
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Cholangioheptatitis in equines.
def
signs (6)
dx (3)
MO (4)
tx (5)
px
- BILIARY disease with obstruction
- infection +/- sludge +/- stone (s)
- inflammatory conditions of proximal GI tract can lead to cholelith formation.
- signs: icterus, photosensitivity, abdominal pain, fever, CNS signs (rare), weight loss
- dx: U/S, biopsy/aspirate, culture
- MO: e coli, enterbacter, clostridium, actinobacillus
- tx: abx (enro or TMP/S + metro), fluids, +/- DMSO to keep sludge from becoming stones, ursodiol, sx for unresponsive/fibrotic
- px: good if tx works within 7-10d.
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Theiler's Disease, aka serum hepatitis
- acute hepatocellular necrosis following serum or plasma administration (occasionally without) like tetanus antitoxin (6-10wks)
- usually in fall
- adult horses
- rapid progression.
- due to equine parvovirus (horses have lots of liver viruses! Nonprimate hepacivirus causes dz but not failure)
- signs: neuro/HE, icterus, discolored urine, colic, sweating.
- high GGT
- tx: supportive for HE (lactulose, fluids with glc and K+, neomycin/rifaximin, laxatives, NSAIDs, pentoxyfilline), fluids, nutritional support.
- Dead or recovering in 3-5d
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Conditions that can cause increased ammonia and HE (10)
- dehydration
- constipation
- hypokalemia
- GI bleed
- infection
- systemic inflammation
- hyponatremia
- low head position
- excessive sedation
- hyperthermia
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Tyzzer's Disease
- Clostridium piliforme
- acute fatal hepatitis and bacteremia in 5-36d foals
- usu March-May
- signs: acute, depression, fever, seizure, icterus, diarrhea, tachycardia, tachypnea.
- Lab: leukopenia, acidosis, hypoglycemia, high GGT, AST, SDH, abnormal bilirubin, PT, PTT
- tx: tetracycline or Ampi + Gentamicin, or TMP/S + pencillin, fluids, nutritional support (branch chain amino acids
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Plants that cause equine liver failure (3)
- pyrrolizidine alkaloids
- alsike clover
- panicum grasses
- generally poor px
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pyrrolidizing alkaloid toxicity
most toxic parts
what it does
signs (5-6)
dx (5)
tx (6)
what not to use
- flowers and seeds most toxic, then leaf, stem, root
- cytotoxic and anti-mitotic (hepatocytes), cumulative
- signs: neuro, icterus, colic, weight loss, photosensitivity. Usu acute regardless of exposure
- dx: signs, opportunity, multiple horses involved, liver biopsy. Can do assay/analysis
- tx: HE, fluids, pentoxyfilline, moderate protein in diet, antioxidants (vit E, Bs, SamE), zinc
- not colchicinepoor prognosis
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Aslike clover hepatopathy in equines
signs (4)
tx (2)
px
- signs: icterus, photosensitization, neuro, colic
- tx: remove from source! Supportive
- px: fair to good
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panicum in equines
- colic, depression, liver failure, photosensitivity
- liver biopsy (fibrosis, mononuclear infiltration)
- kleingrass, switchgrass, fall panicum.
- Remove source, supportive, anti-oxidant
- poor prognosis
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iron toxicity in equines (2 places iron deposits)
- rare
- hemochromatosis: deposition into hepatocytes = toxicity
- hemosiderosis: kupffer cells, no damage to liver
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iron in neonates
- normal at birth, neuro on day 2, dead on day 3
- liver <1/2 normal weight, dark and rubbery. Severe bile ductule proliferation, mild portal tract fibrosis, massive hepatocellular necrosis, lobular collapse
- do NOT give iron-containing products before colostrum! Alzheimer II cells.
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Neonatal Isoerythrolysis and hepatic failure
- increased volume of blood administered = increased liver failure likelihood
- anemic hypoxia vs iron overload
- poor prognosis
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hepatic lipidosis in equines
who
why
what
prevention
px
- ponies, minis, donkeys
- NEB disorder!! Also stress, breed, pregnancy/lactation, obesity, Cushings rarely
- liver swells, fulminant hepatic failure
- prevent: basic attention to nutritional and metabolic needs. Routine health care
- px: good if tx fast!
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Hyperlipemia in horses
signs (3-4)
dx (7 but 3 are easy)
tx (6)
- signs: anorexia, depression/HE, jaundice, colic, ventral edema
- dx: breed, hx, signs, hypertriglyceridemia, hyperlipemia, elevated enzymes, abnormal liver function test
- tx: correct predisposing, nutritional support (FEED - enteral and/or parenteral), supportive (fluids, NSAIDs), insulin CRI, heparin, pergolide for Cushings
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vascular causes of hepatic encephalopathy
- PSS
- portal vein thrombosis
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PSS in equines
signalment
signs
dx
medical, sx tx
- signalment: 6-12wks
- signs: cerebral dysfunction (blind, sz, circling etc)
- dx: signs, high blood ammonia, bile acids, imaging
- medical tx: temporary. Lactulose, abx PO, sz control, laxatives, good carb, low protein forage
- sx tx: ligation, coil or umbrella embolization, cellophane banding, ameroid ring. 50% success
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chronic active hepatitis
- chronic portal inflammation that extends into the parenchyma, with piecemeal necrosis and fibrosis
- cirrhosis: advanced fibrosis leading to function failure
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chronic liver disease
causes
signs
lab
dx
tx
nutrition
avoid
- causes: infectious (bacteria, virus), toxic, immunologic, neoplastic
- signs: clinically silent (elevated enzymes), weight loss, photosensitivity, jaundice, depression, lethargy, anorexia, colic, fever, acute onset of HE
- lab: elevated enzymes (esp GGT but less than cholangitis. Hepatocellular vary). Low BUN, albumin. High globulins, bile acids, direct bilirubin
- dx: biopsy (severity of fibrosis, inflammation, location of dz, biliary stasis, megalocytosis)
- tx: treat initiating, minimize loss of weight and muscles, prevent infection/dermatitis etc, pentoxifylline, abx for neutrophilic (TMS), steroids for lymphocytic, colchicine (anti-fibrotic), SAMe, urodiol, milk thistle for oxidative, zinc
- nutrition: glc and easily digested carbs, modest fat. Lots of calories and protein
- avoid: Cu, Fe, Manganese, Vit A.
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Hepatic neoplasia
- lymphoma
- cholangiocarcinoma (weight loss, appetite loss, hypoglycemia)
- hepatoblastoma
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hepatic encephalopathy
- high concentrations of ammonia passes BBB.
- Systemic inflammation and sepsis from endotoxemia or bacterial translocation, breakdown products of injured hepatocytes, cytokine storm increase ROS causing systemic effects, increases permeability of BBB. Iron is pro-inflammatory
- decrease enteric-derived neurotoxins (ammonia), decreasing cerebral edema, correcting glucose, electrolyte and acid-base, maintaining perfusion and oxygenation. K+, neomycin, lactulose to trap ammonia. Protect from sunlight, Pentoxifylline to stop fibrosis. SAMe to prevent oxidative.
- Sedation may cause lowering of the head, which worsens cerebral edema.
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