GI Ulceration

Question 1

Obj: Risk factors and treatment of gastric ulcers

Answer 1

• ​S

Question 2

Obj: Mechanism of action of anti-ulcer drugs and NSAIDs

Question 3

Obj: NSAID toxicity:

• most common area affected in GIT
• Treatment of gastric vs colonic ulcers
• how to make a diagnosis of NSAID toxicity

Question 4

Obj: How to prevent NSAID Toxicity

Question 5

How is the Equine stomach divided into parts?

Answer 5

• Glandular & nonglandular portions
• separated by the margo plicatus

Question 6

What cells make up the stomach? what are their roles?

Answer 6

• Parietal cells:
  
  • produce HCl
    
    • produced by the H⁺- K⁺- ATPase on luminal side of cell
    • Horses produce HCl continously
  • Stimulated by Vagus nerve (Ach), gastrin and histamine (H2 receptors)
• Chief Cells:
  
  • produce pepsinogen
• Mucus cells:
  
  • Produce mucus
    
    • combines with HCO₃ to form a protective ‘gel’

Question 7

What are the different types of ulcers that affect horses?

Answer 7

• Non-glandular ulcers:
  
  • this portion has less protective factors
    
    • does not have mucus/HCO₃ layer
  • Most protection due to epithelial tight junctions between cells
  • Ulcers are caused by exposure to HCl, pepsin, VFA & Bile acids (duodenal reflux)
• Glandular Ulcers:
  
  • Ulcers result Due to loss of protective factors (mucus/HCO₃ layer and mucosal blood flow)
  • More difficult to treat

Question 8

What are the clinical signs of gastric ulcers in adult horses?

Answer 8

• Non-specific
• Anorexia
• Chronic or intermittent colic
• decreased performance
• ill thrift
• some asymptomatic

Question 9

What are the clinical signs of gastric ulcers in foals?

Answer 9

• bruxism
• salivation
• colicky behavior
• rolling into dorsal recumbency
• interrupted nursing
• weight loss
• diarrhea
• ill thrift
• some asymptomatic

Question 10

What is the concern in foals with clinically ‘silent’ ulcers

Answer 10

Gastric rupture and death possible

Question 11

What is Gastric Outflow Obstruction

Answer 11

• Due to ulcers that stricture in the pylorus or duodenum
  
  • most commonly occur in foals and weanlings
• More severe clinical signs
• poor prognosis

Question 12

How are gastric ulcers diagnosed in horses?

Answer 12

• Gastroscopy - definitive
  
  • Score 0 - 4 (deep ulceration and extensive lesions)
• Fecal occult blood test
  
  • not specific
  • Hemoglobin positive = foregut ulcer
  • Albumin positive = colonic ulcers

Question 13

What are the treatment options for gastric ulcers in horses? How do they work?

Answer 13

• ID and Remove risk factors
• Antacids:
  
  • Temporarily increase gastric pH (2hr)
  • large volume (200ml) q4h
  • not recommended
• Sucralfate:
  
  • Adheres to ulcerated mucosa
  • stimulation of mucus secretion
  • enhanced prostaglandin E synthesis
• H2 Antagonist:
• Proton pump inhibitor:
  
  • Block H⁺ secretion at parietal cell membrane by binding to the H⁺-K⁺-ATPase of the cell
  • Prolonged effect
  • Omeprazole - only FDA approved drug for treatment and prevention against ulcers
• Prostaglandin:
  
  • Misoprostol is a synthetic PGE2 analog
• Feed:
  
  • alfalfa
  • dietary oil

Question 14

What are the most commonly used NSAIDs in horses?

Answer 14

• Phenylbutazone (Bute®)
• Flunixin meglumine (Banamine®)
• Ketoprofen

Question 15

How do NSAIDs work?

Answer 15

• inhibit conversion of arachondonic acid into econsanoids (including prostaglandins and thromboxane) by inhibiting cyclo-oxygenase
• by Decreasing prostaglandins:
  
  • Anti-inflammatory effects
  • attenuate the clinical effects of endotoxin
  • anti-pyretic effects
  • analgesic effects

Question 16

What Cyclo-oxygenases are there? how are they similar/different?

Answer 16

• COX-1:
  
  • constitutively expressed form
  • necessary for homeostasis
  • Found in:
    
    • platelets
    • Kidneys
    • GIT
  • Physiologic affects:
    
    • GIT health
    • protective renal effects
• COX-2:
  
  • inducible form in response to injury - pathologic
  • Produced constitutively in many other organs ( including kidneys of horses
  • Found in:
    
    • fibroblasts
    • chondrocytes
    • endothelial cells
    • macrophages
    • mesangial cells

Question 17

Which cyclo-oxygenase do NSAIDs target?

Answer 17

• Most NSAIDs used in equine medicine are nonselective
• Only Firocoxib is a selective COX-2 inhibitor (approved for use in horses)

Question 18

What are the effects of NSAID toxicity

Answer 18

• Generalized mucosal ulceration throughout GIT
• Right dorsal colitis (ulcers) - most common

Question 19

What are the clinical signs of NSAID toxicity?

Answer 19

• Anorexia
• lethargy
• colic
• diarrhea
• fever
• signs of endotoxemia
• edema
• hypoproteinemia
  
  • hypoalbuminemia
• Electrolyte losses
• prerenal or renal disease
• neutropenia

Question 20

How is NSAID Toxicity Diagnosed?

Answer 20

• clinical signs
• diagnostic tests
  
  • ruling out other disease
• Hx of NSAID use
• Oral exam
• gastroscopy
• ultrasound
  
  • thickened right dorsal colon (>5mm)
  • colonic edema

Question 21

What are the risk factors for developing NSAID toxicity

Answer 21

• Dose:
  
  • high dose & long duration
  • even ‘safe’ doses can induce toxicity
• Age: foals more sensitive (drugs have longer T_½)
• Type of NSAID:
  
  • phenylbutazone > Flunixin > ketoprofen
• Dehydration/hypovolemia

Question 22

What is the treatment for NSAID toxicity?

Answer 22

• Stop ALL NSIADS
• Depends on location:
  
  • Gastric Ulcers (NSAID) - antiulcer medications
  • Colonic Ulcers/Right Dorsal Colitis - more difficult
    
    • Diet change - complete pelleted feed, no/low hay
    • Corn oil - increase linoleic acid and local prostaglandin production)
    • Sucralfate - may help
    • Psyllium mucilloid - may increase production of VFA
  • Renal disease - 2x maintenance of IV fluids (diuresis)
    
    • usually reversible unless oliguric
• Supportive treatment:
  
  • IV crystalloid fluids
  • treat endotoxemia
  • antibiotics
  • analgesics

Question 23

What is the possible sequella of right dorsal colitis?

Answer 23

• Stricture developing as ulcers heals
• may be addressed with surgery
• Prognosis is poor