Gastrointestinal Pathology:
• GIT Development
• Pharmacology: Absorption via GIT + other routes
• Pathology of Alimentary System
• Pathology of Stomach / Abomasum
• Pathology of Intestines + Peritoneal Cavity
• Pathology of Exocrine Pancreas • Pathology of Liver
• Clinical Pathology of GIT
• Clinical Pathology of Pancreatic Disease:
• Pathophysiology of Vomiting + Regurgitation:
• Infectious causes of Prehension Disorders
• Microbial causes of GIT disease: Viruses
• Microbial causes of GIT disease: Bacteria
• Physiology of GIT Pain
• Ruminant GIT Pain: Non-infectious
• Ruminant GIT Pain: Infectious
• Diarrhoea: Pathophysiology
• Diarrhoea: Bacteria
• Diarrhoea: Protozoa
• Diarrhoea: Virus
• GIT Viral Control
• GIT Cestodes (tapeworms) – LA + SA
• GIT Nematodes – LA
• GIT Nematodes – SA
• GIT Trematodes (flukes) – Ruminants
• GIT Parasite Control
• P1) GIT Parasites – anaemia, diarrhoea + ill-thrift
• P2) Alimentary Tract Pathology
• T3) LA Pain – Enteritis, Bloat, Flukes
• T4) SA Pain – Hookworm, Cestodes, Parvovirus
• T5) Comparing sources of Diarrhoea
• T6) Parasite IPM Type Scenario
Introductory lecture:
D Degenerative → chronic organ failureA Anomalous → congenital, colic, oesophagus
M Metabolic → bloat, acidosis, colic
N Nutritional+ neoplastic → sarcomas, colic, food-induced scours
I Inflammatory+ infectious + idiopathic → parasites, pancreatitis / hepatitis, diarrhoea
T Traumatic+toxic → poisons, gut stasis (autointoxication, vomiting)
V Vascular → circulatory thrombosis, horse strongyles
Causing clinical signs → removal metabolites / blood, damager gut lining (protein losing gastro-enteropathy causing hypoproteinaemic oedema), interfering with digestion / absorption (damage), blockage of gut / BD, irritation of mucosa by larvae causing diarrhoea / secretion, migration through gut wall
Production of pathology → toxicity by changing gut structure of flora, migration through tissues / residence in tissue, host reaction with inflammation
Host = ↓ parasite load on host, ↑ immunity, ↓ access to infection (off environment with heavy burden)
Parasite = ↓ no. in environment (desiccation), ↓ access to host, ∆ stock if host specific (sheep → cattle → horse) Control point in HPE:
• ↓ environmental contaminants → ↓ adults in host (H = drench), kill off infective stages (E, P = heat, desiccation), manage intermediate H
• ↓ L3 exposure → pasture environment (E), manage susceptible ind differently (H), clean H2O (flukes)
GIT Development:
Formation of simple gut
→ yolk sac partially internalised as gut lumen, epi lining from endoderm + remainder of wall by splanchnic mesoderm (head = fore-, lateral = mid-, tail = hind-)• During yolk sac invagination, vitelline a. follow → primordium of GIT BV [cranial mesenteric a.]
Attachments:
• Dorsal wall via dorsal mesentery (persists as mesenteries)
• Ventral wall via ventral mesentery (remnant – lesser omentum, falciform ligament, median ligament of bladder) Stomodeum @ proximal foregut
Mid gut elongated outside body cavity (1st trimester) → physiological herniation [jejunum / caecum]
Foregut Pharynx, lower RT, oesophagus, stomach, proximal duodenum, liver, biliary system, pancreas
Midgut Distal duodenum, jejunum, ileum, caecum, proximal colon
Hindgut Distal colon, rectum, anal canal, urinary bladder, urachus, majority urethra
Stomach
→ gut dilation cranial to ST (moves caudally as lungs expand / oesophagus elongates) • Greater curvature moves dorsally• Rotation → entry on L + exit on R:
o 90° on longitudinal axis → greater curvature to L (2nd wk in dog); ruminant compartments
o 90° on dorsoventral axis → distal end from caudal to R (4-5th wk in dog)
o 1st rotation = forms primordium of omental bursa [btw gastric a. + stomach]
o Ruminant → greater curvature = ruminoreticulum; lesser = omasum; distal stomach = abomasum)
Liver:
Hepatic diverticulum → grows from foregut into ventral mesentery + towards ST
• Parenchyma develop from HP → also ventral pancreatic diverticulum + cystic diverticulum [gall bladder] o Endoderm = hepatocytes, bile canaliculi, hepatic ducts
o Splanchnic mesoderm = CT
• During expansion of HD → engulfs vitelline then umbilical v. (= hepatic sinusoids) + other become hepatic portal v. • Ductus venous (within liver primordium) links umbilical v. with caudal VC (provides maternal O2 blood)
• L umbilical v. becomes enlarged + R umbilical v. regresses early • Ligamentous venous → postnatal ductus venous
Primordial liver → relationship to ST via coronary ligaments + L / R ligaments Haematopoietic role → some haematopoietic cell clusters (↑ in foetus) Cystic duct → derived from cystic diverticulum (not in horse)
Pancreas
→ 2 diverticula from foregut forming ventral (R @ DD) / dorsal (L @ stomach) diverticulum • Diverticular fuse as gut expands → becomes complete pancreatic body + lobeso 2 ducts (horse, dog); 1 duct (pig, ruminant, cat – other regresses) • Pancreatic / accessory pancreatic duct @ major / minor duodenal papilla
Midgut
→ U-shaped loop forms when gut elongates at a rate > than body length • Consists of cranial + caudal limb → diverticulum with caudal limb = caecumo Cranial limb = distal duodenum, jejunum
o Caudal limb = ileum, caecum, ascending colon, proximal transverse colon • Connected to yolk sac via narrow stalk regresses during gut elongation
• Cranial mesenteric a. through loop
• Rotation → cranial limb elongated > caudal limb elongation + around cranial mesenteric a. primordium (RoM) o ↑ in pigs → caecum in L – others all on R
• Physiological herniation of midgut through umbilical cord → dog @ 30 dys; pig @ 20 dys o Return with ↓ size of mesonephroni + growth of abdominal wall
o Omphalocele = failure of loop to return
Hindgut
→ distal transverse colon, descending colon, rectum, anal canal, part of UT • Proximal → pushed to L when cranial limb of midgut loop returns• Distal (cloaca) → btw allantoic diverticulum + cloacal membrane
• Urorectal septum:
o Horizontal fold → cranial septum (extends from cranial end of junction of allantoic diverticulum + hindgut toward cloacal membrane)
o Lateral ridges → caudal septum (ridges fuse medially)
• Cloacal division:
o Dorsal → rectum / anus (terminates at anal membrane)
o Ventral → urogenital sinus (terminates @ urogenital membrane – linked to allantois by urachus)
Histogenesis of intestinal wall:
• Temporary occlusion of gut lumen with proliferation of endodermal cells → recanalization via vacuoles o Failure = atresia ani or coli
• Villi formation + cellular differentiation
Pharmacology: Absorption via GIT + other routes:
Xenobiotic absorption = proportion of administered drug that accesses systemic circulation • 𝐵𝑖𝑜𝑎𝑣𝑎𝑖𝑙𝑎𝑏𝑖𝑙𝑖𝑡𝑦 (𝐹) =𝐴𝑟𝑒𝑎 𝑢𝑛𝑑𝑒𝑟 𝑒𝑥𝑡𝑟𝑎𝑣𝑎𝑠𝑐𝑢𝑙𝑎𝑟 𝑟𝑜𝑢𝑡𝑒 𝑐𝑢𝑟𝑣𝑒
𝐴𝑟𝑒𝑎 𝑢𝑛𝑑𝑒𝑟 𝑖𝑛𝑡𝑟𝑎𝑣𝑎𝑠𝑐𝑢𝑙𝑎𝑟 𝑟𝑜𝑢𝑡𝑒 𝑐𝑢𝑟𝑣𝑒
• Don’t always have IV route = poor formulation or toxic (Fluoxetine –thick, viscous, causes ion inbalance) o Calculate relative bioavailability → compare A under extravascular route
o True bioavailability → compare to IV route
Enteral → GIT route
Parenteral route → into GIT other than oral
Oral route = non-painful, easy administration
• Some cause oesophageal irritation → strictures [antibiotics in cats (give with water)] • 75% drug absorbed within 1-3hrs (particularly carnivores) → 3 hrs for emesis if poisoned
Duodenal absorption → depends on:
• Lipid solubility → pH ∆ drug into its uncharged (better) or charged forms
• Whether carrier mediated transport available → ↑ young for Ca channels (susceptible to Pb poisoning – same carriers) • Molecule size → ↑ for small
Factors:
• Gastric → slow gastric emptying ↓ absorption (opioids ↑ pyloric tone + ↓ gastric emptying), low pH can destroy some drugs (penicillins – particularly carnivores)
• Intestinal (no time to absorb)→ ∆ motility ↓ (↑ = hypomotile = hypovolaemia / hypotensions; ↓ = hypermotile = diarrhoea) o ↓ blood in exercise ↓ absorption
• Fibrous food in herbivores = drug meshed in fibrous material • Drug factors = size, tablet compression
• Oral elixa = easier to absorb but if compressed doesn’t work well + enteric protective coating • Metabolism by gut microbes
• Ruminal dilution • Duodenal length
• Fibrous diet can trap drugs in GIT lumen • Differences in transit times in ssp
Ruminate = only parasiticides orally (only things that affect the gut directly) [otherwise everything is IM or SC or IV]
Food + absorption in carnivores → ↑ oral absorption, ↓ irritation (aspirin), some don’t want food • Lipophilic drugs = greater absorption with lipophilic foods
Even if poor oral absorption, some are still orally:
• Aminoglycosides (lipophobic) against gram -ve aerobes
• Neomycin (aminoglycoside) → used topically in GIT, cornea, conjunctive, aural mucoas, skin, intramammary preparations • Hydrophobic
Neomycin → aminoglycoside antibacterial agents (hydrophilic – effective against gram -ve bacteria) • Use = cornea, conjunctiva, aural mucosa, skin, intramammary
• Little oral absorption → inactivated by GIT / liver enzymes + GIT microbes during 1st pass metabolism
Opiods → few orally available (↑ 1st pass metabolism) or ↑ dose required Inhalational administration:
• Volatile general anaesthetic (halothane, isoflurane)
• Nebulisation = aqueous drug dissolved in fine water droplets + inhaled for bronchial disease
IV 100% bioavailability (↓ mg required / kg) - some drugs are not available
- some drugs are only IV → some anaesthetic induction agents (thripentone, propofol) - difficult with hypotension (cardiac arrest) + oedematous tissue (pump heart)
- infusion → small concentration administered continuously (avoid peaks / troughs) → good for rapidly metabolised drugs (dopamine, dobutamine, fentanyl)
SC / IM
IM = better drug absorption SC = less painful
Pharmacology Practical:
Green vomiting = metaldehyde poisoning (snail / slug bait – shaking, frothing at mouth, fever, waning consciousness), grass Red faeces = low intestinal haemorrhage (trauma, infection, rodenticide poisoning (warfarin = anticoagulant → microhaemorrhages become macrohaemorrhages = mostly internal))
Lipophilic drugs → goes everywhere including gut lumen (down concentration gradient)
1) Pharmacokinetic process of absorption → proportion of administered drug / xenobiotic that gets into circulation by any route
2) Difference btw absorption + bioavailability of a xenobiotics → absorption = difficult to measure; bioavailability = how we measure absorption (see absorption, distribution + elimination)
3) Routes for GIT → rectal (poor absorption – anticonvulsants = stimulates defecating + falls out [diazepam] 4) Absorption per os (PO) → duodenum (all ssp)
5) Ssp differences in absorption → transit t, diet (fibrous trapping), microbes, ruminal dilution, duodenal length, metabolism, pH
6) Window of opportunity to induce vomiting / emesis using an emetic → 75% absorbed within 3 hours, so 4 hours
7) When not to induce vomiting → if it causes damage when coming back up (megaoesophagus, corrosive, foreign body (sharps), already vomiting / dehydrated, recent abdominal surgery, ssp can’t vomit)
Emetics at home = hydrogen peroxide, very salty water, mild dishwashing liquid
8) Techniques if animal ingested toxin > 4 hrs ago:
• Fluids
• Gastric lavage (activated charcoal by endotracheal tube = stomach pumping – binds toxins but may cause constipation) • Surgical removal
• Oral chelation for heavy metals (binds to minimise absorption) • Cathartics (reduce transit time – risk dehydration)
• Enemas (not much use – microlax for acute constipation > obstruction) • Stabilise if acutely poisoned (airways, breathing, circulation)
• Decontamination
• Intralipid therapy → IV intralipid emulsion for fat soluble drugs (alcohol toxicity – absorbed very lipophilic drugs) • After metabolism → use CYP450 modulators
• ↑ secretion → ↑ GFR (water soluble substances, IV fluids, contraindicated in anuric patients) = check fluid overload
9) Gastric ulc:
• NSAIDs + glucocorticoids, change in pH / mucosa, long surgery (dehydration), diet (horse – maintain grazing) • CS = inappetence, weight loss, lethargy, vomiting, diarrhoea
• Gastric perforation + peritonitis, septicaemia • ↑ pH = inhibit parietal cells, proton-pump inhibitor • Protect ulc whilst its healing = sucralfate (coats)
• You might use high NSAID for some GIT cancers → co-administer with prostaglandin analogue
10) Reducing gastric acid secretion:
• Proton pump inhibitors → reduce H+ released into lumen
• Histamine 2 receptors inhibitors → no Ac / cAMP to stimulate H+/K+ ATPase receptors
Pathology of Alimentary System:
CS = inappetence, anorexia, vomiting (active - ↓ horse / rat = ↑ cardiac sphincter), diarrhoea, constipation, dysphasia, ptyalism (drooling), halitosis (bad breath), vomiting (active), regurgitation (passive), diarrhoea, chronic weight loss
• Replace lost fluid to maintain diarrhoea (except cholera)
GIT defence → pH, lymphoid tissue, saliva (protect MM → equine gastric ulcers due to dry feed); microflora, secreted Ig, vomit, proteolytic enzymes, ↑ epi turnover (3-4 dys), peristalsis (diarrhoea) to shed pathogen
Oral Cavity:
Defence → SS epi with ↑ regeneration, microflora, taste to reject toxins, saliva with digestive enzymes, pH, mucosal IgA / lysoenzyme secretions
Disrupting microflora = diet ∆, antibiotic use
1) Teeth → causes dysphagia (difficulty eating)
Malocclusion + uneven wear Brachygnathia (short mandible) or prognathia (long mandible) - horse → maxillary molars abrading mandibular mucosa - rodents → overgrown incisors + molars
Enamel hypoplasia Viruses infect ameloblasts during enamel formation (< 6 mths) / before teeth erupt
Retained teeth Deciduous teeth → supernumerary as adults (sharper with gingival step)
2) Mucosal stomatitis → diffuse inflammation
• Direct injury → foreign bodies (grass, bones) + chemicals (detergents, caustics = ulc) • Systemic or local disease:
Vesicular Fluid accumulates in epi then vesicles coalesce → erodes + 2° infection - viral path = FMD, vesicular stomatitis
- CS = anorexia, lameness (vesicles @ coronary band), ↑ morbidity (↓ production + PI)
FMD Picornavirus of cloven-hoofed = ruminants, pigs
- @ lips, buccal, tongue, coronet, interdigital skin, udder
- ↑ morbidity + ↓ mortality → ↓ production due to lameness + can’t eat
- infection via vesicles → inhalation + ingestion causes viraemia + localised @ epi / LN
Autoimmune Pemphigus foliaceous → auto-Ab against keratinocytes’ desmosomes / hemidesmosomes in epi. causing ulc / crusting
Ulcerative or erosive
Can present as end stage vesicular stomatitis but no vesicular stage - uraemia
- virus → feline calicivirus, mucosal disease (BVD), blue tongue, malignant catarrhal fever, equine viral rhinotacheitis
Uraemic Accumulated metabolites due to renal failure (urea breakdown by bacteria → NH3 = ulc)
Papular - contagious ecthyma
- Scabby mouth → Parapox virus that enters via abrasion @ sheep mouth, udder, coronary band + anus (pustules → scabs = eosinophilic cytoplasmic inclusion bodies in early disease)
Suppurative Actinobacillosis (wood tongue) → tongue is enlarged, firm with diffuse fibrous proliferations + granulomas - retropharyngeal LN = multifocal, well demarcated yellow lesions
Eosinophilic granuloma complex
Lesions affect skin, mucocutaneous junction + oral cavity (cat > dog) - reaction pattern rather than disease
- lesions → indolent ulcer (low grade), eosinophilic granuloma (inner thighs), eosinophilic plaque - cats = allergy, insect + inhalant hypersensitivity or autoimmune [genetic]
- indolent ulcers @ skin, mucocutaneous junction, oral cavity, upper lip, hard palate - eosinophilic granulomas @ tongue, palate
- eosinophilic plaques @ abdomen, thighs
Catarrhal WBC + slough cells
Granulomatous Pyogranulomatous with macrophages
3) DoG:
• Oral cancers readily metastasise + invade tissue
Gingival hyperplasia Gingival overgrowth
Brachycephalics → 30% boxers > 5 yrs
Epulis Excessive growth of gingiva = benign except 1 into gingiva
- all benign → acanthomatous epulides (malignant acanthomatous ameloblastomas) - fibrous or fibromatous
- gingival hyperplasia → epulis → fibroma → fibrosarcoma
Papillomavirus Ssp specific → cattle, horse, dog
- hyperplastic lesions (benign hyperplasia) → malignant transformation to SCC (@ cattle UT / GIT → hyperplasia → cysts → cancer)
- self-limiting within 1 yr
Oral melanoma - commonly malignant in dogs
- some are amelanotic → don’t make melanin (pink)
Oral fibrosarcoma - 20% oral tumours in cats
Oral SCC - cat tongues / dog tonsils
Oral chondrosarcoma Oral osteosarcoma
