Pathogenesis of Veterinary Disease

General
Icterus Prehepatic - increased production of circulating bilirubin d/t lysis of erythrocytes
Hepatic - impaired scavenging/processing of bilirubin d/t hepatocellular insufficiency
Posthepatic - impaired excretion of bilirubin d/t biliary disease
Mechanisms of neoplastic Mesothelioma: 1) direct irritation by asbestos, 2) disruption of mitotic spindle by asbestos fibres-aneuploidy,
transformation chromosomal damage, 3) generation of iron-dependent ROS; 4) induces MAPK and ERK-1/2 signaling - stimulation
of c-Jun and AP-1 protooncogenes
 Growth advantage - produce/respond to many growth factors (PDGF-A/B, EGF, TGF-B); may have abnormal
Wnt/Frizzled pathway signalling
 Immortalization - telomerase activity increased in 90% of mesotheliomas
 Absence of Tumor Suppressor Genes - loss of p14, p16 (involved in P53/Rb signaling); loss of NF2-merlin
 Apoptotic Avoidance - increased expression of antiapoptotic Bcl-xL
 Angiogenesis - produce VEGF
 Matrix interactions - express collagens, matrix metalloproteinases
Carney Complex Protein kinase A regulator gene (PKRAR1A) mutation???
Amyloidosis Reactive Amyloidosis - Chronic inflammation > release of IL1& 6 by macrophages > synthesis of SAA by
hepatocytes > limited proteolysis > amyloid deposited as β-pleated sheets in glomeruli, interstitium and/or
tubular basement membrane > protein leakage through damaged glomeruli > proteinuria.
Type I Hypersensitivity Production of IgE antibody → immediate release of vasoactive amines and other mediators from mast cells;
recruitment of inflammatory cells (late-phase reaction)
Type II Hypersensitivity Production of IgG, IgM → binds to antigen on target cell or tissue → phagocytosis or lysis of target cell by activated
complement or Fc receptors; recruitment of leukocytes
Type III Hypersensitivity Deposition of antigen-antibody complexes → complement activation → recruitment of leukocytes by complement
products and Fc receptors → release of enzymes and other toxic molecules
Type IV Hypersensitivity Activated T lymphocytes → i) release of cytokines and macrophage activation; ii) T cell-mediated cytotoxicity
Th1 responses T-helper-1 (TH1) subset  synthesizes and secretes IL-2 and interferon-γ (IFN-γ) but not IL-4 or IL-5  delayed
hypersensitivity, macrophage activation, and synthesis of opsonizing and complement-fixing antibodies, such as
IgG2a in mice, all of which are actions of IFN-γ
Th2 responses TH2 cells produce IL-4, IL-5 and IL-13 but not IL-2 or IFN-γ  synthesis of other classes of antibodies, notably IgE
(mediated by IL-4 and IL-13), activation of eosinophils (mediated by IL-5)
Haptenization Adsorption of a small, nonimmunogenic molecule to a large carrier molecule (such as a protein) to produce an
immunogenic complex, inducing an immune response
Acquired Melanosis (pigs) - ingestion of acorns by genetically predisposed pigs  swine tyrosinase acts on phenolic substances found in
acorns  increase the biosynthesis and the anomalous storage of melanin?

Cancer Biology
Cachexia
Paraneoplastic hypercalcemia ectopic production of Parathyroid-related protein (PTH-rP) - mobilization of
Acute Tumor Lysis syndrome in rapid and widespread lysis of tumor cells  massive release of intracellular components such as nucleic acids,
mice potassium, and phosphorus  disseminated microemboli composed of nuclear and cytoplasmic debris derived
from lysed tumor cells  mechanical obstruction of capillary beds  death
Mechanisms of viral malignant Subgroup J Avian Leukosis virus – associated histiocytic sarcoma – in ovo/neonatal infection  persistent
transformation viremia  ChL5 (myelomonocytic cells and activated T Lymphocytes), CD45 (hematopoietic except erythoid,
platelets), and MHC class II – positive tumors arising from splenic ellipsoids and red pulp  metastasis to liver,
kidney, and other organs
Equine Sarcoid – Bovine Papillomaviruses 1/2 express E5 major transforming oncoprotein  binds PDGF-BR 
activating PI3K-AKT-cyclinD pathway  proliferation ; also activation of activation of phosphor-JNK and phosphor-
JUN
Self-sufficiency in growth Tumors have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation
signals (Oncogenes) - protooncogenes - constitutively expressed  oncoproteins endow cell with self-sufficiency in growth
Growth Factors (PDGF-B/SIS; FGF/HST-1; INT-1; TGF-B/TGF-a; HGF)
 Growth Factor Receptors (EGF-R family/ERB-1/2; CSF-1R/FMS; neurotropic factors receptor/RET; PDGFR; stem
cell factor receptor/KIT)
 Proteins involved in Signal Transduction (GTP-binding proteins/K-RAS, HRAS, N-RAS; nonreceptor tyrosine
kinase/ABL; Ras signal transduction/BRAF; WNT signal transduction/B-catenin)
 nuclear regulatory proteins (C-MYC, N-MYC, L-MYC)
 cell cycle regulators (cyclins/cyclin-D, cyclin-E; cyclin-dependent kinase/CDK4)
Insensitivity to growth- Tumors may not respond to molecules that are inhibitory to the proliferation of normal cells such as transforming
inhibitory signals (tumor growth factor-β (TGF-β), and direct inhibitors of cyclin-dependent kinases.
suppressor genes) - TGF-βreceptor, E-cadherin SMAD 2 and SMAD 4  Growth inhibition, Cell adhesion
Failure of TGF-B signalling (inactive TGF-B receptor, diminished SMAD-2/4)  diminished CDK inhibitors
(Cip/Kip, INK4a)  uncontrolled CDK4 complex formation  failure of brake mechanisms on cell cycle
progression from G1/S

(diminished B-catenin expression) Diminished E-cadherin expression  disaggregation of cells

- NF-1  Inhibition of RAS signal transduction and of p21 cell-cycle inhibitor

Loss of NF-1  diminished neurofibromin  uncontrolled RAS-GTP binding and activation  continuous cell
proliferation signalling

- NF-2  Cytoskeletal stability

Loss of NF-2  diminished merlin  diminished actin-CD44 binding  unstable cell-matrix interactions 
abnormal contact inhibition

- APC/ β-catenin  Inhibition of signal transduction

Diminished APC  failure of downregulation of B-catenin, increased translocation to nucleus  forms
 complex with TCF  upregulation of cMYC, cyclin D1, etc  upregulated cell proliferation

Altered B-catenin - E-cadherin interaction  altered cell adhesiveness

- PTEN  PI-3 kinase signal transduction

Diminished PTEN activity  diminished transcription of p27 Kip/Kip cell-cycle inhibitor and stabilizing protein
 uncontrolled CDK4 complex formation  failure of brake mechanisms on cell cycle progression from G1/S

- RB  Regulation of cell cycle

RB mutation (knock-out or abnormal E2F binding site)  failure of transcription of E2F transcription factors 
uncontrolled CDK4 complex formation  failure of brake mechanisms on cell cycle progression from G1/S

- p53  Cell-cycle arrest and apoptosis in response to DNA damage

- Failure of p53 signalling  diminished CDK inhibitors (Cip/Kip, INK4a)  uncontrolled CDK4 complex
formation  failure of brake mechanisms on cell cycle progression from G1/S

- DNA damage  DNA-dependent protein kinase and ATM (ataxia-telangectasia mutated) activation  lack
of phosphorylation of p53 and protein unfolding  unable able to bind to DNA  fails to stimulate
transcription of several genes that mediate cell-cycle arrest and apoptosis

- WT-1 p16(INK4a)  Nuclear transcription; Regulation of cell cycle by inhibition of cyclin-dependent kinases
Diminished p16(Ink4a) activity  lost capacity to block cyclin D-CDK4 activity and to prevent RB
phosphorylation during the cell cycle

- BRCA-1 and BRCA-2  DNA repair

- KLF6  Transcription factor
Diminished KLF6  decreased transcription of Cip/Kip cell-cycle inhibitor p21

Evasion of apoptosis Tumors may be resistant to programmed cell death, as a consequence of inactivation of p53 or other changes
- BCL-2
Overexpression of BCL-2  accentuated protection from mitochondrial pathway of apoptosis

- P53
Diminished expression of p53  diminished transcription of proapoptotic genes (BAX, BID)

Defects in DNA repair Tumors may fail to repair DNA damage caused by carcinogens or unregulated cellular proliferation
- DNA mismatch Repair Abnormalities: MSH2(2p16), MLH1 (3p21) genes
Failure of nucleotide mismatch repair  progressive accumulation of abnormalities in various genes
(protooncogenes, TSGs)  microsatellite instability

- nucleotide excision repair – failure of repair of pyrimidine crosslinks  impaired DNA replication
- recombination repair
- ATM gene
Diminished expression of ATM (ataxia-telangiectasis) gene  impaired dectection of DNA double-strand
breaks (ionizing radiation, O2 free radicals)  diminished phosphorylation of p53  failure of cell cycle arrest
and apoptosis

- BRCA genes (BRCA-1/2)

Diminished BRCA-1/2 expression  diminished RAD51 binding  impaired repair of double-strand DNA
breaks, chromatin remodelling

Limitless replicative potential – Tumor cells have unrestricted proliferative capacity, associated with maintenance of telomere length and function
Telomerase Enhanced telomerase expression  loss of normal telomere shortening with cell replication  failure of telomere-
mediated, p53-dependent proliferative arrest/apoptosis
Sustained angiogenesis Tumors are not able to grow without formation of a vascular supply, which is induced by various factors, the most
important being vascular endothelial growth factor (VEGF)
- production of angiogenic factors (HIF-1a-mediated expression of VEGF)
- loss of angiogenesis inhibitors – mutation of p53  diminished thrombospondin-1 expression, accentuated
VEGF, HIF-1a
Mechanisms of Tumor metastases are the cause of the vast majority of cancer deaths and depend on processes that are intrinsic
metastasis/invasion to the cell or are initiated by signals from the tissue environment
1) Invasion of Extracellular Matrix: detachment of cells from one another
- (diminished catenin expression ) - downregulation of E-cadherin  diminished homotypic adhesions between
cells
2) attachment ot matrix components
- Atypical expression/distribution of laminin and fibronectin receptors, increased/atypical expression of integrins
 invasion of basement membrane, attachment to ECM components
3) degradation of ECM
- abnormal/enhanced expression of serine, cysteine, matrix metaloproteinases (particularly Type IV collagenases
MMP2, MMP9)
- matrix degradation releases growth promoting, angiogenic/antiangiogenic, chemotactic factors
4) migration of tumor cells
5) Vascular dissemination and homing of tumor cells
- homotypic adhesions between tumor cells, heterotypic adhesions with platelets (promotes survival and
implantability)
- Degradation of ECM (as above)
- CD44 expression (a normal Tcell adhesion molecule used to migrate to selective sites through interactions with
high endothelial venules) – expression may favour metastasis
- tumor metastasis homing mediated by:

Cyclooxygenase activity in
cancer
Alimentary
Palatoschisis (Cleft Palate)
Cheiloschisis (Hare Lip)
Odontoma
Dentigerous Cyst
Diarrhea
Segmental
intestinal/colonic/anal aplasia
(Atresia coli/ani)
Meckel's Diverticulum -
Colonic Aganglionosis (Lethal
White Foal Syndrome)
Equine Dysautonomia (Grass
Sickness)
Mycotic Rumenitis
Rumenal Tympany (Bloat)
MCT-associated duodenal
ulceration
Cardiovascular
Vitamin D-related metastatic
mineralization
Atherosclerosis
Scurvy
Ionophore Toxicosis
E. coli-associated Edema
Disease
Fibrinosuppurative pericarditis Traumatic Reticuloperitonitis/Pericarditis (Hardware Dz) - Ingest wire foreign body > penetrates reticulum
High-Altitude Disease
Viral Vascular Disease
Type III Hypersensitivity
Vasculitis
- adhesion molecule-ligand interactions in endothelium of target tissues
- chemokine receptor expression on tumor cells – homing to tissues in which chemokine ligand is expressed
Sialyl-Lea – E-selectin ligand -
T and Tn antigens -
genetic abnormalities (inherited?); excessive administration of Vit A during gestation (dogs); administration of
cortisone during gestation (Dogs) --> Failure of fusion of lateral palatine processes --> Aspiration pneumonia,
emaciation
Failure of fusion of maxillae along midline (philtrum) --> Aspiration pneumonia, emaciation
hamartoma of enamel organ --> mix of fully-differentiated dental components: Complex - do not form dental
structures; Compound - form numerous differentiated but abnormal dental structures ("denticles")
dental dysgenesis - abnormal proliferation of cell rests of Malassez --> epithelial-lined cyst; may contain
rudimentary/malformed teeth --> may become impacted with keratin; may cause fistula formation
four major mechanisms by which diarrhea may occur:
1) Malabsorption with or without bacterial fermentation  osmotic diarrhea. Generally, this is a problem of the
small intestine, but secondary colonic malfunctions can occur because of malabsorption of bile salts and fatty
acids that stimulate fluid secretion in the large intestine.
2) Hypersecretion by a structurally intact mucosa. This activity results in a net efflux of fluid and electrolytes
independent of permeability changes, absorptive capacity, or exogenously generated osmotic gradients.
3) Exudation caused by increased capillary or epithelial permeability (protein-losing enteropathy).
4) Hypermotility (increased rate, intensity, or frequency of peristalsis)  decreased mucosal contact time,
digestion and absorption of nutrients should be less efficient  decreased motility in some diseases allows for
increased bacterial proliferation; some enterotoxins can stimulate intestinal motility
- segmental ischemia
- peritonitis
- failure of development of luminal epithelial primordium
retention of stalk of yolk sac  omphalomesenteric duct remnant (blind-ended sac near termination of ileum)
White patterned horses (esp. vero foals). Ile118Lys endothelin receptor B (EDNRB) mutation --> failure of
migration of neuroblasts from neural crest - congenital lack of myenteric and/or submucosal plexuses in distal
colon/anus - contracted/nonperistaltic distal colon - proximal megacolon (Model for the Hirschprung aganglionosis
of humans).
Unknown pasture toxin > Toxic intestinal ganglion cell necrosis > progressive craniocaudal impaction. Seasonal.
Hares also affected.
Grain overload > rumenal acidosis > mucosal damage > opportunistic fungal inf > vasculitis > ischemia &
mucosal ulceration
Bloat, Primary or frothy - ingestion of legumes > stable foam formation > foam obstructs cardia and inhibits
normal eructation > rumenal distention > respiratory distress > death from anoxia
Bloat, Secondary - Failure of eructation (vagal indigestion) > distention of rumen > respiratory distress > death
due to anoxia
Bloat line - Bloat > elevated intra thoracic pressure > decreased venous return (passive congestion) > cyanosis
of extra-thoracic (cervical) esophageal mucosa and pallor of intra-thoracic esophageal mucosa
Mast Cell Tumor somewhere in body > histamine release > ↑ gastric parietal cell HCl secretion > pyloric mucosal
damage & ulceration
Chronic granulomatous disease (M. avium paratuberculosis) - Macrophages Produce Vit D Analog > Aortic
Mineralization
Hypothyroidism or DM > ↓ lipoprotein lipase activity > ↑ cholesterol > atherosclerosis
Guinea pig, P, red-vented bulbul bird, northern shrike, Indian pipstrels, channel catfish, & primates normally lack
L-Gulonolactone Oxidase necessary for Vit C synthesis
Pathogenesis: Lack L-Gulonolactone Oxidase > dietary Vit C defic > ↓ lysine & proline hydroxylation > impaired
Type 1 & 4 collagen synthesis > weakened vessel walls (physeal cartilage deformity) > periarticular hemorrhage
(&/or osteochondrodysplasia)
Toxic exposure to Lasalocid/Monensin > Exchange of cations for protons across cell membranes without using ion
channels > decreased ATP production, increased ATP utilization (to maintain cation concentrations) > cell death >
Myocardium necrosis and fibrosis
Edema of Eyelids, Mesocolon, Gallbladder, Glandular Portion of Stomach, Mesenteric LNs, Larynx, & Lungs;
Hydrothorax & Hydropericardium; Bilaterally Symmetric Brainstem Malacia
E. coli Inf > Shiga-like toxin prod > endothelial damage > ↑ vascular permeability > edema (various tissues)
In brain: Shiga like toxin type IIe > Necrosis of smooth muscle cells in the arteriole and arteries > vascular
compromise > infarction
wall & diaphragm into pericardium > fibrinous pericarditis & epicarditis
High altitude > chronic hypoxia > pulmonary artery vasoconstriction > right ventricular hypertrophy & failure >
chronic passive congestion > edema
Bluetongue - Culicoides (midge, gnat) bites sheep > hematopoietic cell viral replication > viremia > widespread
endothelial cell viral replication & damage > hemorrhage, edema, thrombosis, & infarction - Hemorrhage at the
Base of the Pulmonary Artery; Rumenal Pillar Hemorrhage & Necrosis
Non-effusive FIP - Coronaviral inf of møs > weak cell-mediated immune response > virus persists in møs >
pyogranulomatous inflam (non-effusive form)
Purpura Hemorhagica - Streptococcus equi equi Ag/Ab complexes. Ag/ab complex vasculitis.
Aleutian Mink Disease - Parvoviral inf of lymphocytes >viral release > immune complex deposition in vessels,

Parasitic Vascular Disease
Human Familial hypertrophic
cardiomyopathy
Human familial dilated
cardiomyopathy
Boxer arrhythmogenic right
ventricular cardiomyopathy
Marfan Syndrome
Coagulation
Vitamin K-deficient
hemorrhagic diathesis
Saddle Thrombus
Simmental Thrombopathia
Rambouillet Sheep
Coagulopathy
Disseminated Intravascular
Coagulation
Hepatobiliary-associated
hemorrhagic diatheses
Uremic coagulopathy
Hemophilias
Inherited Thrombasthenia
Hypercoagulability of
glomerular disease
Endocrine
Mature onset diabetes for the
Young (MODY)
Ferret Hyperadrenocorticism
Primary Hyperparathyroidism
Hyperplastic Goiter
Thyroid peroxidase deficiency
in Rat Terriers, Toy Fox Terrier
Multiple Endocrine Neoplasia
Syndrome in cats, humans
Diabetes Mellitus
Diabetes Insipidus
Cushing's Disease
Hypothyroidism
Hyperthryoidism
Haemolymphatic
Congential Erythrocytic
Porphyria
Protoporphyria
Pyruvate Kinase Deficiency
Phosphofructokinase deficiency Point mutation in M gene for erythrocyte/muscle phosphofructokinase deficiency  haemolytic anemia,
Estrogen Myelotoxicosis
glomeruli, & other tissues > plasmacytic vasculitis, GN, splenomegaly/hepatomegaly, & hypergammaglobulinemia
Effusive FIP - Coronaviral inf of møs > no cell mediated response > viremia > non-neutralizing antibodies
deposited in vessel walls > fibrinonecrotic peritonitis & vasculitis (effusive form)
Strongylus vulgaris infarcts - Ingestion of L3 larvae of Strongylus vulgaris > larvae enter wall of cecum and
colon and molt to L4 larvae > penetrate arterioles > migrate up the vessel along the intima > localize in cranial
mesenteric artery and its branches along the aorta > arteritis, thrombosis + aneurysm > + emboli to small and
large intestine > intestinal infarction and abdominal pain (colic).
AD; various mutations involving sarcomeric proteins of cardiac myocytes (Cardiac B-myosin heavy chain; Cardiac
troponin T; Cardiac troponin I; A-tropomyosin; Ventricular myosin essential light chain; Cardiac myosin-binding
protein C)
Documented mutations in dystrophin, myosin
AD; humans – mutations in ryanodine receptor 2 gene and desmoplakin gene
Mutation in Fibrillin Gene  abnormal collagen crosslinking?  megaloglobus, ectopia lentis; degeneration of
elastic laminae  aortic, pulmonary arterial, coronary arterial dissecting aneurysm and rupture
Ingest rodenticide/clover > coumarin toxicity > ↓ Vit K > ↓ Vit K-dep coag factors (II, VII, IX, & X) > hemorrhage
Feline - HCM --> left atrial enlargement>blood turbulence/stasis > thromboembolism formation > distal aortic
and ilial thrombosis (Note: Sometimes assoc w/ hyperthyroidism)
Calcium diacylglycerol guanine nucleotide exchange factor I mutation  ????
Mutations in g-glutamyl carboxylase deficient??  diminished vitamin K-dependent coagulation parameters
1) failure of metabolism of vitamin K
2) failure of synthesis of coagulation factors (all but Factor 8), anticoagulant factors, fibrinolytic factors
3) failure of scavenging of activated coagulation factors, anticoagulant factors (such as FDPs), fibrinolytic factors
Protein-losing nephropathy  loss of antithrombin III in the urine  hypercoagulable state(  atrial thrombosis
(hamsters))
Inactivating mutations for Beta cell function (human):
- glucokinase  rate-limiting step for glucose metabolism in beta cells
- insulin gene transcriptional regulators PDX1, HNF1a, HNF4a
Adrenal cortical hyperplasia/adenoma/carcinoma > estrogenic hormone secretion > swollen vulva, hypocellular
marrow, nonregen anemia, & alopecia
cytochrome b5 (cyt b5)  allosteric regulator that selectively enhances the 17,20-lyase activity of
P450c17  androgen synthesis
Functional parathyroid adenoma/adenomatous hyperplasia > excessive PTH secretion
Clinicopathologic Findings: Hypercalcemia, hypophosphatemia, elevated alkaline phosphatase due to bone
resorption.
Iodine Defic, Goiterogenic Agents (Brassica sp., Sulfonamides, Thiouracil, etc.), Iodine Excess, or Congenital
Enzyme Defect Affect Hormone Synthesis (Corriedale, Dorset Horn, Merino, & Romney Sheep, Afrikander Cattle, &
Saanen Dwarf Goats)
Pathogenesis: Any of the above causes >inadequate thyroxine synthesis > ↓ free T4 & T3 > stim TSH secretion
> follicular cell hypertrophy & hyperplasia
AR Thyroid peroxidase deficiency  congenital hypothyroidism  CNS hypomyelination
Menin gene mutations  development of multiple tumors in parathyroid, pituitary, pancreatic endocrine tumors
Shorthorns, Holsteins – AR hereditary deficiency of uroporphyrinogen III cosynthase > Defective heme synthesis >
accumulation of porphyrin pigment in bone or teeth, porphyrinuria, epidermolysis and exudative dermatitis
(photosensitization), and hemolytic anemia
Limousins - deficiency of ferrochelatase > accumulation of protoporphyrin in the skin > absorption of UV light
energy by protoporphyrin > epidermolysis and exudative dermatitis (photosensitization) (NO discoloration of
teeth, urine, or anemia)
Pyruvate kinase deficiency  Diminished ability to synthesize ATP  diminished erythrocyte lifespan 
osteosclerosis, hemochromatosis, myelofibrosis
hemosiderosis, EMH, slowly-progressive myodegeneration with myocyte vacuolation and PAS-positive, diastase-
resistant inclusions
Ferret - prolonged estrus - prolonged Hyperestrogenism – bone marrow suppression/toxicosis – thrombocytopenia,
anemia – hemorrhages
Anemia of Chronic Disease
Acute intravascular hemolysis Equine Lentivirus (EIA) - Virus adsorbed on erythrocytes > IgM, IgG attachment to virus > complement
Hemolytic anemia in Japanese Lack band 3 integral protein (necessary to link lipid bilayer of erythrocyte membrane to cytoskeleton) 
Black Cattle
Neonatal isoerythrolysis
Severe Combined
Immunodeficiency (SCID)
Bovine Leukocyte Adhesion
Deficiency
Hepatobiliary
Hepatic Lipidosis
Hepatic Glycogenosis
Pyrrolizidine Alkaloid Toxicosis Crotalaria, Senecio, Cynoglossum, Heliotropium, Echium,, Amsinckia, Symphytum ingestion > Cytopathic effect
Corriedale sheep
hyperbilirubinemia
Congenital Erythrocytic
Protoporphyria in Limousin,
Blonde d’Aquitaine cattle
Glycogen storage disease type Hepatic and renal G-6-Pase deficiency  accumulation of glycogen and lipid in hepatocytes, RTE; hypoglycemia
Ia (Maltese)
Familial AA Amyloidosis
(Familial Mediterranean Fever)
Human Wilson Disease
Bedlington terrier copper-
associated hepatopathy
Copper Storage Disease
Human Hemochromatosis
A1 antitrypsin deficiency
Biliary Toxicosis
Hemosiderosis/haemochromato AR abnormality in HFE gene  diminished hepcidin activity?  enhanced absorption from GIT  iron
sis
Hepatosis Dietetica
Clostridial Necrotizing Hepatitis Bacillary Hemoglobinuria (Red Water) - Dormant Clostridium haemolyticum spores in Kupffer cells > hepatic
Hepatic
Fusobacteriosis/Actinomycosis
Ascites
Increase in IL-1, IL-10, TNF-a, IFN-g --> increased production of Ferritin, Transferrin, Divalent Metal Trasporter 1
--> increased iron storage in RES  inhibition of erythropoiesis (reduced EPO receptors, secretion; reduced Stem
Cell Factor; apoptosis)
Increase in IL-6, action of LPS --> increased production of hepcidin --> decreased iron absorption, increased
sequestration in RES (inhibition of Ferroportin)
Increase in TNF-a, erythrophagocytosis --> decreased RBC half-life
activation > hemolysis; bone marrow hyperplasia and then atrophy; ag-ab membranous glomerulonephritis; virus
within macrophage cytoplasm (ISH)
haemolytic anemia, stunted growth
Mare sensitized to fetal RBC sire inherited-antigens in utero > foal ingests anti-RBC antibodies in colostrum > IV
hemolysis > icterus, hemoglobinemia, hemoglobinuria, splenomegaly, & anemia w/ erythroid marrow hyperplasia
Arab foals - V(D)J gene defect > blocked development of B & T lymphocytes > Immunosuppression >
Opportunistic adenovirus and Pneumocystis carinii pneumonia
Holstein calves – AR inherited single point mutation (adenine to guanine) at position 383 of the CD18 gene 
impaired expression of the beta2 integrin (CD11a,b,c/CD18) of the leukocyte adhesion molecule on neutrophils 
failure of extravasation of neutrophils  persistent marked neutrophilia  bacterial infections, delayed wound
healing and stunted growth  ulcers on oral mucous membranes, severe periodontitis, loss of teeth, chronic
pneumonia and recurrent or chronic diarrhea
Guinea Pigs, Rabbit, Cow, Ferret, Cat, Horse, Sheep, Macaque, & Camelids: Obese animal > anorexia
(after parturition in dairy cattle, before parturition in beef cattle, during preg & lactation in horses, during preg in
rabbits & GPs, & with Vit B12 & cobalt defic in sheep) > ↑ adipose tissue lipid mobilization > overwhelms
hepatocellular FA oxidation & VLDL formation > hepatocellular lipid accum
Watanabe rabbits - genetic defect in low-density lipoprotein receptor gene causing hypercholesterolemia,
hepatic lipidosis
Diabetes Mellitus - Reduced insulin-dependent glucose uptake by cells  accelerated lipolysis from adipose
tissue
Hyperglycemia secondary to diabetes mellitus > glucose uptake by the liver (not insulin-dependent as in in
muscle, fat, fibroblasts) > excess intrahepatocellular glucose stored as glycogen.
and mitosis inhibition causing hepatic portal fibrosis with bile duct hyperplasia and megalocytes. (Also
photosensitivity dermatitis).
Mutation in canalicular multispecific organic anion transporter (cMOAT)  accumulation of black pigment in
hepatocyte lysosomes
Ferrochelatase deficiency  accumulation of protoporphyrin pigments in portal regions, Kupffer cells, sinusoidal
endothelium, hepatocytes
Mutation of Pyrin gene expression  inadequate inhibition of IL-1B activity (human)
AR mutation of WD gene  dysfunction of ATP7B cationic transport protein  abnormal secretion and excretion
of copper
AR abnormality in MURR1 gene  abnormal segregation of copper in hepatocytes
Sheep - simple Cu excess in diet OR Mb deficiency OR pyrollizidine alkaloid ingestion > chronic accumulation of
copper in liver > sudden release of copper into vasculature > intravascular hemolysis with release of hemoglobin
> acute tubular necrosis, hemoglobinuria, hepatic necrosis
AR abnormality in HFE gene  diminished hepcidin activity?  enhanced absorption from GIT  iron
accumulation
Deficient secretion of a1 antitrypsin  cirrhosis, accumulation of PAS-positive, diastase-resistant material (altered
forms of a1-antitrypsin) in hepatocytes
Facial Eczema of Sheep - ingestion of dead rye grass (Lolium) infected with Pithomyces chartarum fungi that
produces sporodesmin toxin > necrotizing cholangiohepatitis > cholestasis > increased phylloerythrin due to
decrease excretion > UV light activation > cutaneous free radical production > facial eczema
accumulation (human)
Vit E/Selenium defic > peroxidative damage of capillary membranes > ↑ vascular permeability, thrombosis, &
ischemia > tissue necrosis
injury from Fasciola hepatica migration > ↓ oxygen tension > spore germination > Phospholipase C toxin prod >
hepatocellular necrosis & IV hemolysis > icterus, hemoglobinemia, & hemoglobinuria
Black Dz (Infectious Necrotic Hepatitis) - Dormant Clostridium novyi (usually Type B) spores in liver> hepatic
injury from Fasciola hepatica migration > ↓ oxygen tension > spore germination > toxin prod > hepatocellular
necrosis
Damaged rumenal mucosa > bacterial invasion > spread to liver via portal vein > hepatic necrosis
Mechanical and dynamic influences on blood flow through a damaged liver (fibrosis and nodular
expansion impede blood flow, dynamic influences of stellate cell contraction and hepatic vein smooth muscle that
affect portal venous pressure)  portal hypertension
+ Increased generation/impaired clearance of Various factors that regulate splanchnic blood flow
(including histamine, nitric oxide, endothelins, atrial natriuretic peptide (ANP), calcitonin gene regulated peptide
(CGRP), TNF-α, substance P and vasoactive intestinal peptide (VIP), produced locally in splanchnic circulation,
normally cleared by liver)
 Increased splanchnic arteriolar blood flow

Ductal Plate malformations
Cytochrome P450-related
intoxication
Direct Hepatotoxicity
Smooth Endoplasmic Reticulum
Induction
DNA adduct formation
Toxic Induction of
Autoimmunity
RNA interference
Hepatic Arteriovenous Fistula Acquired (subsequent to abdominal trauma, rupture of hepatic artery aneurysms, secondary to hepatic vein
obstruction or cirrhosis with extreme portal hypertension)  Mixing of higher pressure arterial blood with venous
blood  retrograde flow into portal vein, arterialization of portal circulation, development of portal hypertension
 opening of vestigial, low-resistance collateral extrahepatic portosystemic communications (acquired
extrahepatic shunts).
Glycogen storage disease
type Ia
(von Gierke's disease)
Metabolic Diseases
Hypoglycemia
Hyperglycemia
Lactic Acidosis
Integumentary
Epitheliogenesis Imperfecta
Ehlers-Danlos syndrome
Ichthyosis
Pemphigus complex diseases
 increased hydrostatic pressure in splanchnic capillaries
 over-production of splanchnic lymph
 increased portal pressure, sodium retention, increased cardiac output,
 induced contraction of stellate cells and intrahepatic vascular smooth muscle, could restrict venous outflow
through established portosystemic collateral veins
+ Reduced synthesis of albumin and globulins by failing liver  reduced vascular oncotic pressure
+ Dysregulation of autonomic regulation of splanchnic blood flow
Disruption or failure of the epithelial-mesenchymal interaction during fetal development of the liver 
 congenital hepatic fibrosis (CHF; calf), Caroli disease, von Meyenburg complexes, Caroli syndrome (dogs, rats),
autosomal recessive polycystic kidney disease (ARPKD), and autosomal dominant polycystic kidney disease
(ADPKD; mice, pck strain), biliary atresia (dog,foal)
Loss-of-function mutations in hepatic and renal glucose-6-phosphatase (G6Pase)  increased hepatic glycogen
storage, diminished blood glucose
- hypoglycaemia of hepatic insufficiency: severe diffuse hepatic necrosis 
1) inadequate gluconeogenic enzyme activity for conversion of amino acids to glucose
2) reduced functional hepatic mass for sufficient gluconeogenesis
3) insufficient storage of glycogen to sustain euglycemia between interdigestive intervals
4) abnormal response to glucagon
- dogs with large hepatic tumors (hypoinsulinemia)
- beta cell tumors, rare non-beta cell tumors
- rare congenital enzyme deficiencies; usually suggested by abnormal glycogen retention:
- glucose-6-phosphatase deficiency – impaired hydrolysis of glucose-6-phosphate to glucose;
accumulation of glycogen in liver
- amylo-1,6-glucosidase deficiency (debrancher enzyme) – impaired conversion of glycogen to
glucose-6-phosphate
- lysosomal acid alpha-glucosidase deficiency – glycogen accumulation
- hyperglycemia of hepatic insufficiency
- defective insulin metabolism  peripheral hyperinsulinemia  overcompensation of catecholamines,
glucocorticoids, glucagon  hyperglycemia during fasting period
- Inadequate delivery of O2 to tissues
- stagnant hypoxia (shock, vascular occlusion)
- demand hypoxia (strenuous exercise)
- repiratory hypoxemia
- hemoglobic hypoxia (anemia, methemoglobinemia)
- Increased production by metabolic pathways
- grain overload
- defective metabolic pathways for aerobic glycolysis
- Hyperammonemia – urea toxicosis, , ammoniated forage toxicosis
- pyruvate dehydrogenase deficiency
- lactic acidosis of hepatic insufficiency
- metabolism of lactate to glucose may be compromised with severe liver disease
- others - sepsis, canine babesiosis, transfusion of stored blood or packed RBCs
AR or spontaneous mutation
Deficiency of enzyme amino procollagen peptidase (which is required for oxidative deamination of terminal lysine
residue on procollagen > defective cross-linkage of collagen > weak abnormal collagen
Failure of dissolution of desmosomes > retention of keratinized cells > icthyosis > death from septicemia in
calves and dogs
Pemphigus foliaceus - Autoimmune breakdown of intercellular attachments via IgG attach of desmoglein 1 
intracorneal pustular (and acantholytic) dermatitis with alopecia and crusts
Bullous Pemphigoid - IgG bind to the bullous pemphigoid antigen II, a collagen type 17 present within
hemidesmosomes of the lamina lucida of the basement membrane zone > subepidermal clefting

Mechanobullous Disease
Photosensitization
Necrotizing Steatitis
Cutaneous Infarction
Epidermolysis bullosa simplex Mutations in basal cell keratins 5 and 14  abnormal assembly of keratin intermediate filaments  cytolysis of
Junctional epidermolysis
bullosa
Dystrophic epidermolysis
bullosa
Epidermolysis Bullosa Acquisita production of autoantibodies against collagen VII (normally forms the fibrous 2-dimensional network of lamina
Bovine Collagen dysplasia
Proteoglycan deficiency
Waardenburg syndrome
Peibaldism
Albinism
Chediak-Higashi syndrome
Uveodermatologic Syndrome immune-mediated attack against melanin or melanocytes
(Vogt-Koyanagi-Harada-like
syndrome
Laminitis
Muscular
Ischemic Myopathy
Malignant Hyperthermia/PSS
Clostridial myositis
Masticatory Myositis
White Muscle Disease
Pemphigus Vegetans - Autoimmune breakdown of intercellular attachments via IgG attach of desmoglein 3
(dogs – desmoglein-1)  suprabasilar pustular (and acantholytic) dermatitis with mucosal ulceration
Defective development and / or deficiency of hemidesmosomes > mild mechanical trauma leads to detachment
of basal cells from basement membrane > bulla formation > sloughing of skin, foals slough hooves. Seen in foals,
sheep, dogs.
Primary (St. John's Wart, Buckwheat, phenothiazine, tetracycline, thiazides, sulfonamides), Secondary
(hepatogenous), & Inherited (Bovine Congenital Porphyria in Holsteins & Shorthorns & Bovine Erythropoietic
Protoporphyria in Limousins)
Photosensitization, primary, type I - ingestion of Hypericum/Fagopyrum à ultraviolet light exposure à
activation of photodynamic compounds deposited in skin à free radical production à cutaneous necrosis (non-
pigmented areas)
Photosensitization, sedondary/hepatogenous, (type III) - ingestion of Brachiaria
decumbens/Senecia/Crotalaria à liver damage with cholestasis à Accumulation of phylloerythrin > UV light
exposure > activation of the photodynamic agent à ulcerative photodynamic dermatitis
Inherited: Defect in Uroporphyrinogen III Cosynthetase (Bovine Congenital Porphyria) or Ferrochelatase (Bovine
Erythropoietic Protoporphyria) > defective heme synthesis > photodynamic agent accum (porphyrin) >
photosensitization
Vit E/Selenium defic > peroxidative damage of capillary membranes > ↑ vascular permeability, thrombosis, &
ischemia > tissue necrosis
Ergotamine Toxicosis - Ingestion of plant containing Claviceps purpura > Ergotamine toxin > vasoconstriction
& thrombosis of pedal vessels > gangrenous pododermatitis
Frostbite - Cold temp > vasoconstriction > ischemia & necrosis
Erysipelothrix rhusiopathiae inf > septicemia > dermal vasculitis, thrombosis, & necrosis > cutaneous
infarcts
Other Causes of Gangrenous Pododermatitis: Fescue Toxicity
basal cells  intraepidermal clefting
Deficiency or abnormality in one of the hemidesmosome-associated proteins (laminin-5, collagen 17(aka BPAG2
or BP180), integrin a6B4, LAD-1)  subepidermal clefting at lamina lucida in BM
Mutation in the anchoring fibril protein type 7 collagen (COL7A1 in cats)  subepidermal clefting in superficial
dermis, below lamina densa
densa) in sublamina densa anchoring fibrils  autoimmune subepidermal blistering disease(collagen IV IHC -
detected more commonly above subepidermal vesicles than below)
Mutation in gene for procollagen I N-proteinase (excises amino-propeptide of type I and II procollagens)
abnormal collagen precursor molecules  abnormal assembly of collagen fibers (ribbon-shaped) with
diminished tensile strength  dermatosparaxis
Mutation of gene that codes proteoglycan core molecule
Cats - AD mutation with complete penetrance  melanocytopenic hypomelanosis; incomplete penetrance for
deafness
Horses (Waardenburg Type 4 (Hirschprung disease))  White patterned horses (esp. vero foals). Ile118Lys
endothelin receptor B (EDNRB) mutation --> failure of migration of neuroblasts from neural crest - congenital lack
of myenteric and/or submucosal plexuses in distal colon/anus - contracted/nonperistaltic distal colon - proximal
megacolon (Model for the Hirschprung aganglionosis of humans).
Mutations in gene excoding c-kin TKR, gene for stem cell factor (receptor ligand)  diminished proliferation and
survival of malenoblasts  localized melanocytopenic hypomelanosis
Mutation in tyrosinase gene lack of activity  absent melanin synthesis
Mutation in beige gene (involved in generating cellular organelles)  formation of giant melanosomes 
diminished secretion to keratinocytes  color dilution
- two basic hypotheses, vascular and toxic-metabolic:
- vascular hypothesis  digital ischemia is the primary event
- toxic-metabolic hypothesis  direct damage to epithelial cells of the laminae or to the basement membrane,
and that the vascular lesions are secondary
Downer Cow Syndrome - hypocalcemia – weak cow – downer cow – pressure-induced muscle ischemia –
necrosis
Deep Pectoral Myopathy of Turkeys, Chickens - excessive exercise > swelling of supracoracoid and
pectoralis profundus muscles > compression of muscle within tight osteofascial compartment > vascular
occlusion > ischemia > coagulative necrosis of muscle (Zenker’s necrosis).
Ryr-1 (ranitidine) gene mutation (encodes Ca release channel) > defective ryanodine receptor > Halothane
anesthesia or stress > ↑ Ca release & muscle contraction > ↑ O2 & glycogen consumption & ATP depletion>
necrosis & hyperthermia
Blackleg - Ingestion of spores of Clostridium chauvoei > deposition in muscle > trauma or transient ischemia to
muscle > anaerobic environment > growth of latent spores > secretion of cytolytic exotoxins (lecithinases,
hemolysin, deoxyribonuclease, hyaluronidase) > necrosis of endothelium and myofibers
Circulating antibody to Type IIM myofibers in masticatory muscles (masseter, temporal, & pterygoid muscles) >
immune complex deposition > myositis & myofiber atrophy
Vit E/Selenium defic > peroxidative damage of capillary membranes > ↑ vascular permeability, thrombosis, &
ischemia > tissue necrosis
Contagious Foot Rot
Caprine Myotonia
Miniature Schnauzer myotonia AR mutation in skeletal muscle voltage-dependent chloride chanel (ClC-1) (see Malignant Hyperthermia below)
Malignant Hyperthermia
X-linked Muscular Dystrophy
Nemaline Myopathy
Hyperkalemic Periodic Paralysis AD mutation in muscle sodium channel  increased open time and sodium influx  compensatory loss of muscle
Congenital Muscular
Hyperplasia
Polysaccharide Storage
Myopathy
Knockdown Syndrome
Myopathy in Turkeys
epidermal maceration > invasion of F. necrophorum > induction of interdigital dermatitis > secondary infection
with B. nodusus > necrosuppurative digital dermatitis +/- extension to underlying tissues with osteomyelitis,
tenosynovitis, and arthritis
AD mutation in skeletal muscle voltage-dependent chloride channel ClC-1  causes decreased skeletal muscle
chloride channel conductance  ionic instability of sarcolemmal membrane  myotonia
Mutation in gene encoding skeletal muscle calcium release channel (RYR1)  hypersensitive and heightened
ligand-gating of the Ca-release channel  sustained increase in cytoplasmic Ca levels and subsequent activation
of the actin-myosin contractile proteins  depletion of glycogen stores, hypoxemia, and accumulation of heat,
hyperkalemia, lactic acid, and metabolic and respiratory acidosis
X-linked mutation in genes (xmd) encoding Dystrophin  progressive myodegeneration
Three mutations (slow alpha tropomyosin 3, nebulin, actin)  contractile dysfunction and rod formation
(composed of a-actinin)  progressive myodegeneration
potassium  may further activate sodium channels  altered resting muscle membrane potential  increased
muscle action potentials – muscle fasciculations and spasms
Deficient activity of myostatin  unregulated skeletal muscle
AD mutation in glycogen synthase I gene (GYS1)  accumulation of polysaccharide within skeletal myocytes
monensin in feed  induce lower hepatic concentrations of vitamin E  predispose the turkeys to skeletal
myopathy

Nervous
Coup-contrecoup Cerebral 1.Head freely movable.
contusions 2.Head accelerated rapidly (by being struck by a broad object, such as an automobile) or decelerated rapidly
(head strikes pavement after a fall from a standing position).
3.Because the brain does not fill the cranial vault, it may lag behind the movement of the cranium when the head
is accelerated or decelerated rapidly.
4.As a result, the inside of the cranial vault may strike the stationary brain at the point of impact (coup injury), or
the lesion may occur on the opposite side (contrecoup), either from the stretching and tearing of vessels at that
site or by the brain being struck by the inside of the cranial vault on the opposite side when there is reduced
amount of cerebrospinal fluid buffer present.
Cerebellar Hypoplasia Cerebellar hypoplasia, BVD: In utero viral inf > inf & necrosis of cerebellar external germinal cells > defective
Purkinje cell localization & maturation > cerebellar hypoplasia
Bovine- in utero infection of Bovine Pesti Virus (BVD), Akabane virus;
Cat- Feline panleukopenia virus (in utero);
Sheep- Border disease (Pestivirus),Cache valley fever virus;
Dog- Segmental hypoplasia - canine herepes virus, canine Parvo virus;
Pig- Hog cholera virus (Pestivirus),sows treated with organophosphate during pregnancy;
Goat- Cache valley fever virus, copper deficiency;
Birds- Fowl glioma- inducing virus (avian leucosis virus group A)
Hydranencephaly/Porencephaly Bluetongue In utero viral inf around 40-75 days gestation > inf & necrosis of undiff cerebral subventricular cells >
cerebral cavitation
Cyclopia ingestion of Veratrum californicum by dam between 9-14 d gestation > steroidal alkaloids (Cyclopamine and
jervine, potent teratogens) > inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic
development) > inhibit neural tube development > cyclopia, CNS malformations, arrhinencephalia
Spina bifida Separation Defect in fusion site I of neural tube
Leukoencephalomalacia Ingest moldy corn w/ Fusarium moniliforme > Fumonisin B1 toxin > inhibition of ceramide synthesis > cytotoxic
sphinganine & sphingosine accum > vascular and direct cellular toxicity > leukoencephalomalacia
Focal Symmetric Lambs - Fed on lush pasture or high grain diet > Clostridium perfringens Type D intestinal overgrowth > epsilon
Encephalomalacia toxin activated by trypsin > endothelial damage > ↑ vascular permeability & edema > focal brain hypoxia &
necrosis
Nigropallidal encephalomalacia in horses - Centaurea solstitialis (Yellow star thistle) OR Centaurea repens
(Russian knapweed) chronic ingestion (repin, a sesquiterpene lactone) > gluthatione depletion > increase of
reactive oxygen species (ROS) > bilaterally symmetric necrosis of the globus pallidus and substantia nigra
Polioencephalomalacia Dietary deficiency of thiamine OR thiamine destruction by sulfites OR diet containing thiamine antagonists OR
grain overload w/reduction in number of microorganisms that synthesize thiamine and an increase in
microorganisms that produce thiaminase > reduction in thiamine > decreased thiamine pyrophosphate > low ATP
(Thiamine is a cofactor in the hexose monophosphate shunt, the metabolic pathway for glucose in the brain, and
the Krebs cycle) > reduction in sodium-potassium pump > loss of osmotic control > cell swelling and necrosis of
neurons > increased intracranial pressure and laminar cortical necrosis (CCN)
In canine ,fox,cat,mink – chastek paralysis (absolute dietery requirement) CAUDAL COLLICULI (mid brain)
In ruminants- 1, Thiamine deficiency 2. Water depriviation –Na+ toxicosis 3. High S intake 4. high CHO diet –
acidosis –Rumen microflora alteration
Feline Ischemic Aberrant cerebral Cuterebra larva migration > thrombosis & occlusion of middle cerebral artery > cerebral
Encephalopathy ischemia & necrosis
Botulism zinc-binding metalloprotease - cleaves specific proteins on synaptic vesicles - prevents release of acetylcholine
from vesicles at nerve terminals - flaccid paralysis
Tetanus wound - innoculation of bacteria into tissue - proliferation and death of bacteria - production of toxin
Tetanospasmin - absorbed by local motor nerves zinc-binding metalloprotease - cleaves synaptobrevin on
synaptic vesicles - inhibition of glycine, GABA release by inhibitory neurons ("Renshaw cells") - extensor spasm,
hyperesthesia
Bovine Citrullinaemia Abnormal activity of arginosuccinate synthetase  accumulation of citrulline  CNS – astroglial swelling; Liver –

Maple Syrup Urine Disease
Ceroid Lipofuschinosis
Primary Hyperoxaluria in the
cat
Lafora Disease
Feline Toxic Peripheral
neuropathy
Rosenthal Fiber
Encephalopathy
Polyarteritis nodosa
Hepatoencephalopathy
Salt Intoxication
Status spongiosus
Neuroexcitotoxicity
Metabolic Polyneuropathy
Domoic Acid
STORAGE DISEASES
Sphigolipidoses
GM1 Gangliosidosis
GM2 Gangliosidosis
Glucocerebrosidosis
Type A and B
Sphinogomyelinoses
hepatocellular hydropic swelling
Branched chain ketoacid decarboxylase deficiency  elevated leucine, isoleucine, valine  Myelin sheath
splitting (status spongiosis)
Recessive defect in lysosomal or mitochondrial function; deficiency in palmitoyl protein thioesterase in some 
accumulatioof sphinoglipid activating proteins A and D, subunit c of mitochondrial ATPase Cerebral atrophy,
lipofuschin accumulation
Deficient activity of D-glycerate dehydrogenase  L-glyceric aciduria, hyperoxaluria, heavy deposition of oxalate
crystals in renal tubules; neurofilamentous accumulations and Wallerian degeneration in proximal axons of spinal
motor neurons, ventral roots, intramuscular nerves and dorsal root ganglia
Mutations of EPM2A (Laforin) and EPM2B (Malin) (humans)
Inherited deficiency of D-glycerate dehydrogenase  focal swelling and accumulation of neurofilaments in axons
and motor nerves  Wallerian degeneration
AD mutations in genes encoding GFAP cytoskeletal protein  accumulation of disorganized fibers in axons 
formation of eosinophilic deposits (Rosenthal Fibers)  neurologic dysfunction
Ammonia toxicity - shunting or hepatic failure  dietary ammonia that bypasses removal on first pass through
hepatic portal circulation  accumulates in general circulation, crosses blood-brain barrier  encephalopathy:
 decreased expression of microsomal Na-K-dependent ATPase in brain
 ATP consumption in glutamine production -  ATP availability
  excitability (mild ↑ in NH3)
 disturbed malate-aspartate shuttle  ↑ glycolysis
 brain edema (acute liver failure)
  glutamate, altered glutamate receptors
  BBB transport of glutamate, tryptophan, octopamine
 CNS tissue lacks mechanisms for urea cycle – metabolizes ammonia via astrocytic enzymes glutamine
synthetase and dehydrogenase to form glutamine – toxic?
 Elevated blood ammonia is postulated  accumulation of glutamine in astrocytes 
osmotic stress and astrocyte swelling  consequences of which include altered gene
expression, changes in multiple neurotransmitter systems, and brain edema
 Ammonia can be directly neurotoxic
• altering neurotransmission
• potentially contributing to cerebral energy failure - inhibition of -ketoglutarate
dehydrogenase, a rate-limiting enzyme in TCA cycle
↓ alpha-ketoglutarate  Diversion from Urea Cycle for NH3 detoxification  ↓ ATP availability
Glutamine  altered BBB amino acid transport
Aromatic Amino Acids   neurotransmitter synthesis; ↓ DOPA;  Altered neuroreceptors;  ↑ production of
false neurotransmitters
Short-chain Fatty Acids  decreased expression of microsomal Na-K-dependent ATPase in brain; uncouples
oxidative phophorylation  impairs oxygen utilization; displaces tryptophan from albumin - ↑ free tryptophan
False Neurotransmitters - Tyrosine  Octopamine  impairs norepinephrine action; Phenylalanine 
Phenylethylamine  impairs norepinephrine action; Methionine  Mercaptans; synergistic with other toxins (NH3,
SCFA); gut-derived  fetor hepaticus; ↓ microsomal Na-K-dependent ATPase in brain
Tryptophan  Directly neurotoxic; ↑serotonin inhibition
Phenol (derived from Phenylalanine, Tyrosine)  Synergistic with other toxins;  ↓ a multitude of cellular
enzymes  neurotoxic and hepatotoxic
Bile Acids  Membranocytolytic effects alter cell/membrane permeability  BBB more permeable to other HE
toxins  impaired cellular metabolism due to cytotoxicity
GABA  hyperpolarize neuronal membrane  neural inhibition; ↑ BBB permeability to GABA in HE
Endogenous Benzodiazepines: hyperpolarize neuronal membranes  neural inhibition
Hypoglycemia: severe diffuse hepatic necrosis  hypoglycaemia (below)  convulsions
1) inadequate gluconeogenic enzyme activity for conversion of amino acids to glucose
2) reduced functional hepatic mass for sufficient gluconeogenesis
3) insufficient storage of glycogen to sustain euglycemia between interdigestive intervals
4) abnormal response to glucagon
Initial dehydration phase (osmotic loss of water from brain secondary to an increased blood sodium
concentration)  influx of ionic sodium, potassium, chloride into brain  inhibits anaerobic glycolysis  influx or
production of organic molecules (amino acids, polyols, methylamines)  osmoles result in cell swelling upon
rehydration  osmotic differential cannot be equalized quickly enough to prevent edema of the brain  clinical
signs and typical lesions result
-
- degenerative cardiomyopathy (proposed pathogenesis) - primary or at least initial direct interaction of domoic
acid with receptors that are suspected to exist in the heart  myocardiocyte apoptosis
AR B-galactosidase deficiency  accumulation of GM1 ganglioside Neurons have foamy or granular cytoplasm
AR B-hexosaminidase deficiency  accumulation of GM2 ganglioside Neurons have foamy or granular
cytoplasm
Deficiency of glucocerebrosidase (catalyzes conversion of glucocerebroside to ceramide)  accumulation
eosinophilic cytoplasmic vacuoles in cytoplasm of neurons (PAS-), hepatic Kupffer cells (PAS+)
Deficient activity of sphinomyelinase  accumulation of Gangliosides, cholesterol, shingomyelin in neurons,
macrophages in liver, spleen, lymph node, adrenal, bone marrow, lung – expansion of organs by foamy
macrophages
Niemann-Pick type c disease
(Type C Sphingomyelinosis)
Galactosialidosis
Galactocerebrosidosis (Globoid AR Galactosylceramidase deficiency  abnormal myelination, accumulation of Galactosylceramide and
cell leukodystrophy)
Glycoproteinoses
a-mannosidosis
Acquired a-mannosidosis
B-mannosidosis
a-L-fucosidosis in English
Springer Spaniels
Mucopolysaccharidoses
N-acetylglucosamine-6-
sulfatase deficiency (Nubian
Goat) (Sanfillipo Disease,
MPSIII)
Arylsulfatase-B deficiency
(Siamese and shorthairs)
(Maroteaux-Lamy syndrome,
MPSIV)
B-glucuronidase-deficient
mucopolysaccharidosis (Sly
disease, MPSVII)
Glycogenoses
a-1,4-glucosidase deficiency
Amylo-1,6-glucosidase
deficiency (glycogen storage
disease type III)
Polyglucosan body disease
(glycogen storage disease type
IV)
Myophosporylase Deficiency
(Type V glycogenosis)
Acid Maltase Deficiency
Mucolipidoses
Mucolipidosis II
Murine Mucolipidosis Type II
Murine Mucolipidosis Type II
Ophthalmic
Primary Glaucoma
Secondary Glaucoma
Cataract
Marfan Syndrome
Retinal Atrophy of Irish Setters AR mutation in cGMP phosphodiesterase beta-subunit gene (PDE6B)  diminished hydrolysis of cGMP toxic
(Rod-Cone dysplasia type
1/rcd1)
Rod-Cone degeneration in
miniature poodles, cocker
spaniels, others
Ocular albinism and
hypopigmentation
Coloboma
Deficient activity of a cholesterol transporter, NPC1 protein, or a soluble lysosomal cholesterol-binding NPC2
protein  accumulation of Gangliosides, cholesterol, shingomyelin in neurons, macrophages in liver, spleen,
lymph node, adrenal, bone marrow, lung – expansion of organs by foamy macrophages
Combined deficiency of B-galactosidase and a-neuraminidase activity
Galactosysphongosine  toxic to oligodendroglia  Hypomyelination, globoid cell accumulation (macrophages)
inherited galactocerebrosidase deficiency > accumulation of psychosine in the lysosomes of macrophages
(globoid cells) and necrosis of oligodendrocytes > demyelination
Deficiency in a-mannosidase  accumulation of mannose-containing oligosaccharide in secretor epithelial
neurons, endothelia, mixed macrophages, fibrocytes; +/- hypomyelination
Ingestion of swainsonine in Astralagus/Oxytropis/Swainsona > inhibition of lysosomal alpha-mannosidase >
accumulation of alpha-mannosidose within lysosomes > acquired alpha-mannosidosis
Deficiency in B-mannosidase  accumulation of mannose-containing oligosaccharide; hypomyelination
AR deficiency of a-L-fucosidase  accumulation of fucose-containing compounds as glycosylasparagines in
neurons, astrocytes, microglia, perivascular macrophages; accumulation of macrophages and myxoid perineureal
ground substance in nerves
N-acetylglucosamine-6-sulfatase deficiency  accumulation of heparin sulphate as lucent flocculent material in
lysosomes in arterial smooth muscle, cardiac myocytes, fibroblasts, macrophages, hepatocytes, Kupffer cells,
chondrocytes; accumulate of PAS+ gangliosides in neurons (interference with neuraminidase activity)
Arylsulfatase-B deficiency  accumulation of heparin sulphate as lucent flocculent material in lysosomes in
arterial smooth muscle, cardiac myocytes, fibroblasts, macrophages, hepatocytes, Kupffer cells, chondrocytes
B-glucuronidase deficiency  widespread neurovisceral storage, cytoplasmic inclusions appear empty or with
sparse granular-lamellar material; excrete excess chondroitin-6-sulfate and chondroitin-4-sulfate in urine
AR deficiency in a-1,4-glucosidase  glycogen accumulation in skeletal and cardiac muscle, neurons, glia, liver,
elsewhere
Amylo-1,6-glucosidase deficiency  glycogen accumulation in liver, muscle, myocardium, neurons, glia
Deficiency of glycogen-branching enzyme  polyglucosan bodies in neurons, liver, myocardium
Deficient myophosphorylase activity  Accumulation of glycogen in muscle, neurons
Deficient Acid maltase activity  accumulation of glycogen in skeletal muscle, myocardium, neurons
AR Amylo-1,6-glucosidase deficiency  retinal degeneration, accumulation of oligosaccharides,
mucopolysaccharides, lipids in bone, cartilage, skin, connective tissues; occasional lipid inclusions in
cerebrocortical neurons, sciatic nerve axons
Mutation in gene encoding a/B subunit precursor for ClcNAc-1-Phosphotransferase  retinal degeneration,
accumulation of oligosaccharides, mucopolysaccharides, lipids in bone, cartilage, skin, connective tissues;
occasional lipid inclusions in cerebrocortical neurons, sciatic nerve axons
Mutation in gene encoding g subunit precursor for ClcNAc-1-Phosphotransferase  retinal degeneration,
accumulation of oligosaccharides, mucopolysaccharides, lipids in bone, cartilage, skin, connective tissues;
occasional lipid inclusions in cerebrocortical neurons, sciatic nerve axons
absence or underdeveloped outflow tracts with incomplete cleavage of iridocorneal angle.
NZW rabbits: autosomal recessive with incomplete peneterance
Lens Luxation - may involve several factors including anterior dislocation of the vitreous causing pupillary block
and accumulation of degenerate zonular material within the trabecular meshwork
Neovascular Galucoma  Tissue Hypoxia (retinal detachment, iridociliary tumor)  evolution of angiogenic
factors into vitreous/aqueous humor  angiogenesis within anterior iris  formation of fibrovascular memebrane
over anterior surface of iris and drainage angle
Diabetic Cataract - Excess glucose due to hypoinsulinemia or insulin insensitivity > shunts to sorbitol synthesis >
excess sorbitol increases lens osmotic pressure > increased uptake of water > hydropic degeneration and rupture
of lens fibers > diabetes cataract
Mutation in Fibrillin Gene  abnormal collagen crosslinking?  megaloglobus, ectopia lentis; degeneration of
elastic laminae  aortic, pulmonary arterial, coronary arterial dissecting aneurysm and rupture
effecs to outer retinal segments
Diminished incorporation of docoshexaenoic acid into outer rod segments?
Mutation of SLC24a5 cation carrier  hypopigmentation of iris, ciliary body, RPE, reduced size and pigmentation
of melanosomes in melanocytes, other neural crest-derived cell lines
Otic
Waardenburg syndrome
Pancreatic
Zollinger-Ellison Syndrome
Pancreatitis, acute
Reproductive - Male
Freemartinism
Acquired Feminization
Cystic Prostatic Hyperplasia
Spermatic Granuloma
Reproductive - Female
Pyometra
XXY syndrome
Male Pseudohermaphroditism
(Androgen Insensitivity)
XX sex reversal
XY sex reversal
Ovarian/Parovarian Cysts
Cystic Uterine/Vaginal
Structures
Persistent Estrus
Mastitis
Cystic Endometrial Hyperplasia
Respiratory
Familial Neonatal Respiratory - SP-A deficiency is associated with bronchopulmonary dysplasia and/or increased susceptibility to bacterial
Distress
Atrophic Rhinitis
Guttural Pouch Mycosis
Laryngeal Hemiplegia (horses) Trauma to the left recurrent laryngeal nerve. (e.g. pressure by abscesses in strangles due to Streptococcus equi,
Toxic Pneumonitis
Primary Ciliary Diskinesia
Ectodyplasin-1 deficiency
Bronchiectasis
Bronchiolitis obliterans
Emphysema
Pulmonary Dysmaturity
Recurrent airway
obstruction (horse)
Cats - AD mutation with complete penetrance  melanocytopenic hypomelanosis; incomplete penetrance for
deafness
Function gastrin-producing beta cell tumor > hypergastrinemia > hypersecretion of gastric acid > severe gastric
ulceration
meal high in fat > intrapancreatic activation of phospholipase and elastase > pancreatic damage > release of
inflammatory mediators > necrotizing pancreatitis with hemorrhage and fat saponification
Female fetus co-twin w/ male > placental vascular anastomoses & shared hormones (anti-Müllerian hormone) >
masculinization of female genital tract
Sertoli Cell Tumor > Hyperestrogenism, Elevated Inhibin > Gynecomastia, Myelotoxicosis (Non regenerative
anemia, Thrombocytopenia, Granulocytopenia), Squamous metaplasia of Prostate gland acini
Ferret - Hyperestrogenism (adrenocortical tumor) - squamous metaplasia of glandular prostate epithelium +
keratin & pus filled cyst
Release of spermatozoa into interstitium (trauma, necrosis) > highly sulfated amino acid content (similar to
keratins) + immune-privileged tissue niche > immune recognition and Th1 response - granuloma formation
Persistant corpus luteum – Increase Progesterone- Increase endometrial gland activity, decrease myometrial
activity – colonization of bacteria from urinary tract, decrease uterine leukocyte response and maintains closed
cervix,glandular secretions enhance bacterial growth
XXY karyotype  male phenotype
Tfm mutation – deficiency in intracellular androgen receptors  insensitive to masculinising effects of normal
androgens  female external genitalia (blind-ended vagina), nor female internal genital structures, testes in
ovarian position, no male accessory sex glands
Abnormal masculinising gene (Sxr, SOX9; polled gene)
AD or Y chromosomal mutation  XY karyotype with female phenotype
infection
- SP-B mutations result in alveolar proteinosis, failure of formation of tubular myelin, and/or diffuse alveolar
damage
- SP-C mutations in humans cause fibrosis of alveolar septa with infiltration of mononuclear cells (similar to
idiopathic pulmonary fibrosis)
- SP-D deficient mice develop alveolar lipidosis with type II pneumocyte proliferation
Bordetella bronchiseptica inf allows Pasteurella multocida inf > Type A & D toxin prod > degen of osteoblasts &
chondroblasts > turbinate bone resorption (osteopenia)
Aspergillus nidulans guttural pouch infection> erosion of int. carotid artery > hemorrhage
idiopathic) > demyelinization and axonal degeneration in nerve > neurogenic atrophy of left cricoarytenoideus
dorsalis muscle > lack of laryngeal dilatation on inspiration > distension of lateral ventricles of larynx > roaring
Cattle - Ingest L-Tryptophan (in lush pasture (rape, kale & turnip tops) or foggage) > converted to 3 methylindole
in rumen >carried in blood to lung > further metabolized by Clara cells > free oxygen radical formation > Type I
pneumocyte injury & necrosis > edema, hyaline membranes, & emphysema > Type II pneumocyte hyperplasia
(Ingestion of stinkwood (unidentified toxins), Perilla mint (Perilla mint ketone), & moldy sweet potatoes (4
ipomeanol), Micropolyspora faeni spore hypersensitivity (bovine farmer's lung), smog, pit gases, BRSV infection, &
reinf w/ Dictiocaulus viviparus cause similar lesions)
AR inherited defects in one of hundreds of proteins that comprise the structural or functional (motile) components
of cilia/flagella  impaired motility of respiratory, urogenital, otic, retinal, ventricular, embryonal cilia, sperm
flagella  respiratory infections, inner ear infections, situs inversus, hydrocephalus
X-linked mutation of ED-1 gene (TNF-related signalling molecule involved in ectodermal development) 
hypotrichosis, hypodontia, reduced eccrine glands, respiratory squamous metaplasia with rhinotracheitis, lack of
respiratory mucous glands
Various factors that increases the recruitment of macrophages and leukocytes in the lungs (cigarette smoking,
pollution, or defects in the synthesis of antiproteases, such as homozygous α1-antitrypsin deficiency)  imbalance
between proteases released by phagocytes and antiproteases produced in the lung as a defense mechanism (the
protease-antiprotease theory)  proteolytic destruction of alveolar walls
induced by persistent/repeatedexpsoure to allergens (dust, molds, pollens, bacterial components  mucus
hyperproduction, neutrophilic inflammation, bronchoconstriction; smooth muscle hyperplasia, fibrosis, lymphoid
hyperplasia; diminished expression of Clara cell secretory protein with disease  diminished anti-inflammatory
activity
Skeletal
Osteogenesis Imperfecta
Arthrogryposis
Metaphyseal Growth Arrest
Lines
Rickets
Reptile Metabolic Bone Disease Dietary vitamin D3 deficiency &/or lack of UVB light > ↓ intestinal Ca absorption > ↓ plasma Ca > ↑ PTH > ↑ Ca
Articular Gout
Fibrous Osteodystrophy
Human Achondroplasia
Spider Lamb syndrome (Ovine AR point mutation in FGFR3 gene + mechanical stress  abnormal development of ossification centers in bones
Chondrodysplasia)
Osteogenesis imperfecta
Porcine Scurvy
Complex Vertebral
Malformation
Pituitary Dwarfism
Osteochondrosis
COL1A1 or COL1A2 gene mutations > defective Type I collagen > impaired lamellar bone formation & osteopenia
Cause: Akabane virus > Loss of ventral motor neurons- Denervation muscle atrophy- arthogryposis (fixation of
hind limb joints)
Blue tongue, Lupine (Anmodendrine), Poison Hemlock
Autosomal Recessive (Charolais Breed)
Malnutrition > ↓ cartilage growth > ossification > improved nutrition > resumption of cartilage growth & growth
arrest line formation
P or vit D deficiency > inadequate mineralization of physeal cartilage > blood vessels cannot penetrate the
maturing cartilage and primary spongiosa (spicules of cartilage) cannot be resorbed > persistence of primary
spongiosa and cartilage cores within secondary spongiosa > osteoid fails to be mineralized > osteodystrophy with
osteopenia
resorption from bone >↓ bone density > replacement by fibrous CT (fibrous osteodystrophy)
metabolic defect in the secretion of urates by the kidney tubules due to genetics or high protein diet > chronic
hyperuricemia > deposition of urates in synovium and periarticular tissues > urate granuloma formation >
articular swelling
Renal dz/nutritional defic > Ca/P imbalance > ↑ PTH > ↑ Ca resorption from bone >↓ bone density >
replacement by fibrous CT
Mutation in cartilage fibroblast growth factor receptor 3  diminished response to growth signals.
developing by endochondral ossification postnatally
AD (rarely AR) mutations in collagen I genes (COL1A1 and COL1A2)  abnormal Type I collagen synthesis 
diminished osteoid matrix synthesis  excessive bone/dental fragility, joint laxity, blue sclera
Spontaneous AR mutation in L-gulonolactone oxidase  diminished synthesis of ascorbic acid  deficiency in
hydroxylysine  diminished synthesis/deposition of collagen, diminished intermolecular cross-links between
collagen fibers; also impaired differentiation of osteoblasts, hypertrophy of chondrocytes  impaired
endochondral ossification  metaphyseal subperiosteal hemorrhage, osteopenia; diminished ossification of zone
of provisional calcification, increased medullary mesenchyme
monogenic autosomal recessive hereditary defect; point mutation from G to T at nucleotide position 559 in bovine
solute carrier family 35, member 3 gene (SLC35A3)  changes amino acid sequence of uridine 5'-diphosphate-N-
acetylglucosamine transporter protein from a valine to a phenylalanine in position 180  proportional dwarfism,
symmetrical arthrogryposis, multiple malformations of cervical and thoracic parts of vertebral column

Urinary
Chronic Renal Failure Stage 1 (Diminished Renal Reserve) – progressive renal disease  acute loss of nephrons  diminished GFR
without loss of urea/creat clearance or loss of concentrating ability
Stage 2 (Renal Insufficiency) – sufficient loss of nephrons  loss of concentrating ability (polyuria,
isosthenuria), urea/creat excretion (azotemia)
Stage 3 (Renal Failure) – persistent poly/isosthenuria, azotemia, inadequate control of water/electrolyte
balance  uremia, electrolyte imbalances
Stage 4 (End-stage renal failure, oliguric or anuric renal disease) – few nephrons filter plasma  marked
azotemia, oliguria/anuria with isosthenuria
Azotemia Def’n – intravascular increase in nitrogenous wastes (normally excreted by kidneys)
Prerenal azotemia – functional hypovolemia, anemia  diminished renal perfusion  reduced renal filtration +
ischemic injury to RTE  azotemia
Azotemia of hypoadrenocorticism – Aldosterone deficiency  impaired renal excretion of K+ 
bradycardia  decreased cardiac output; diminished renal retention of Na+  diminished renal retention of
H2O   functional hypovolemia  prerenal azotemia
Azotemia of protein-losing nephropathy – glomerular loss of albumin  hypoalbuminemia  decreased
plasma colloidal osmotic pressure  functional hypovolemia  prerenal azotemia
Renal azotemia – injury to nephrons (loss, hypoperfusion, diminished glomerular permeability, increased renal
interstitial pressure, increased intratubular pressure)  decreased GFR  azotemia
Postrenal azotemia – obstruction of flow of urine within lower urinary tract (ureters, bladder, urethra)  release
of vasoactive substances (angiotensin, prostaglandins)  constriction of glomerular arterioles  decreased GFR;
transient increase in tubular hydrostatic pressure  decreased GFR
Nonobstructive postrenal azotemia - accumulation of urine in abnormal body spaces (peritoneum, soft
tissues)  passive absorption of urea, creatinine into blood (in peritoneum, urea equilibrates faster than
creatinine)
Uremia Def’n – “urine in the blood”; clinical signs reflecting renal failure
Ulcerative and necrotic stomatitis – ammonia concentration and secretion in saliva  physicochemical injury to
oral mucosa and blood vessels  necrosis
Atrial and aortic thrombosis – endothelial and subendothelial injury
Hypoplastic anemia – increased erythrocyte fragility  increased turnover; diminished renal EPO secretion 

Visceral Gout
Emphyematous Cystitis
Hemoglobinuria/Hemoglobinuri Bacillary Hemoglobinuria (Red Water) - Dormant Clostridium haemolyticum spores in Kupffer cells > hepatic
c nephrosis
NSAID-induced Renal Papillary NSAID admin > inhibits COX 1 & 2 > inhibits prostacyclin (PGI2) > renal vessel vasoconstriction > renal papillary
Necrosis
Glomerulonephritis
Protein-losing Nephropathy
Hypercoagulability of
glomerular disease
Renal Amyloidosis
Enzootic Hematuria
X-linked Hereditary
Nephropathy of Samoyeds
Polycystic Renal Disease
Congenital Cystinuria
Pyelonephritis
Renal Cyst formation
Urolithiasis
Hydronephrosis
Gentamycin Toxicosis
Acetaminophen Toxicosis
Renal Hypertension
Infectious Disease (Bacterial)
E. coli
diminished BM erythropoiesis
Soft tissue mineralization – Altered Ca-Ph metabolism  mineralization of blood vessels in lungs, stomach,
pleura, kidneys
Uremic gastric ulceration –
Renal secondary Hyperparathyroidism - Chronic renal disease > decreased production of calcitriol by kidney
and hyperphosphatemia > decreased intestinal absorption of Ca, hypocalcemia due to systemic precipitation,
decreased inhibition of PTH secretion > increased PTH secretion > bilateral parathyroid hyperplasia;
Clinicopathologic findings: Hypo- to normocalcemia, hyperphosphatemia, nonregenerative anemia
Fibrous Osteodystrophy – Chronic Renal dz/nutritional defic > Ca/P imbalance > ↑ PTH > ↑ Ca resorption from
bone >↓ bone density > replacement by fibrous CT
Other lesions – myocardial necrosis, ulcerative endocarditis, ileus,
renal failure due to infectious/nutritional/toxic> decreased urate excretion > hyperuricemia > urate deposition on
visceral organs such as liver/myocardium/spleen or serosal surfaces like pleura/pericardium/air sacs
Glucosuria due to Diabetes Mellitus or Fluid Administration > Infection of Urinary Bladder with Glucose-
Fermenting Bacteria > Emphysema in the Bladder Wall
injury from Fasciola hepatica migration > ↓ oxygen tension > spore germination > Phospholipase C toxin prod >
hepatocellular necrosis & IV hemolysis > icterus, hemoglobinemia, & hemoglobinuria
Copper Toxicosis (sheep) - High copper &/or low molybdenum diet > hepatocellular copper accum >
hepatocellular insult > copper release > lipid peroxidation of RBCs > IV hemolysis & hemoglobinuria
Red Maple (Acer rubrum) Toxicosis (horses)- Ingestion of wilted red maple leaves > oxidative damage >
methemoglobinemia, formation of Heinz bodies, and hemolysis > renal hemoglobin casts and tubular
degeneration due to vasoconstriction, hypoxia, direct toxic effects of bilirubin
ischemia & necrosis
Protein-losing nephropathy  loss of antithrombin III in the urine  hypercoagulable state(  atrial thrombosis
(hamsters))
Glomerular amyloidosis > proteinuria (also renal papillary necrosis if interstitial) > ↓ plasma albumin > ↓ plasma
colloid osmotic pressure > edema (anasarca) (Note: In female hamsters, often assoc w/ left atrial thrombosis)
chronic ingestion of Bracken Fern > Quercetin (carcinogen > TCC)
X-linked mutation in exon 35 of COL4A5 gene (encodes alpha 5(IV) collagen chain  suspected to lead to
inadequate corsslinking of type 4 collagen in glomerular BM  failure of transition from a1/a2 to a3/a4/a5 network
of type 4 collagen  progressive glomerulosclerosis, mulitlaminar splitting of lamina densa of BM with electron-
dense particles between splits
AD or AR mutations of PKD genes  altered polycystin protein production  altered cell-cell and cell-matrix
interactions; altered tubular epithelial growth and differentiation  cyst formation in kidneys, liver; occasionally
pancreas (AD)
AR Nonsense mutation of Slc3a1 gene  defective renal resorption of dibasic amino acids (lysine, arginine,
ornitine, cysteine  predisposed to urolithiasis
Cystitis + endotoxemia (from infecting gram-negative bacteria)  diminished competency of vesiculoureteral
valve and abnormal ureteral peristalsis  reflux of bacteria-contaminated urine to renal pelvis and collecting
ducts
+/- urethral obstruction  increased pressure within urinary bladder  enhanced vesiculoureteral reflux
Four mechanisms of renal cyst formation are considered plausible:
1.Obstruction of nephrons can cause increased luminal pressure and secondary dilation.
2.Modifications in extracellular matrix and cell-matrix interactions result in weakened tubular basement
membranes allowing saccular dilation of tubules.
3.Focal tubular epithelial hyperplasia with production of new basement membranes, increased tubular secretion,
and increased intratubular pressure causes development of enlarged, dilated tubules.
4.Dedifferentiation of tubular epithelial cells results in loss of polarity of cells with abnormal cell arrangements in
tubules, reduced tubular fluid absorption, increased intratubular pressure, and dilation of tubules.
Enteroinvasive E. coli - ingestion and intestinal colonization by ETEC à expression of E.coli attaching and
effacing factor (EAE) and secretion of shiga-like toxin 1or2 > necrosis of enterocytes > necrotizing and ulcerative
enteritis
Enteroadherent/Enteropathogenic Collibacillosis - attach to microvillus border of enterocytes and gall
bladder epithelium (cups and pedestals, via intimin) - loss of microvillus structure - loss of glycocalyx digestive
enzymes - maldigestive/malabsorptive diarrhea
Enterotoxigenic Colibacillosis (Neonatal enteritis) - ETEC colonize small intestine via fimbria (F4, 6,18) >
enterotoxin LT 1 activatation of adenylate cyclase causing increased cAMP AND enterotoxins ST 1&2 activate
guanylate cyclase causing increased GMP > increased secretion of Cl, Na, HCO3, water into lumen (secretory
diarrhea)
Enterotoxemic Colibacillosis (Edema disease) - ingestion and intestinal colonization by F18ab positive
enterotoxigenic E.coli > expression of E.coli attaching and effacing factor (EAE) and secretion of shiga-like toxin
IIe variant (Verotoxin) > toxin binds to globotriaosylceramide receptors on endothelial cells > widespread
vascular damage and edema (mesocolon, eyelid, etc)
Enterohemorrhagic E. coli - attach to microvillus border of enterocytes and gall bladder epithelium (cups and
pedestals, via intimin-HP90 receptor binding) - tyrosine phosphorylase activity - increases intracellular Ca -
releases inositol phosphate - loss of microvillus structure; release of bacterial hemolysin - mucosal absorption -
necrosis
Salmonella adhesion of bacteria to apical membranes of intestinal M cells, enterocytes, goblet cells - secretion of endotoxins,
verotoxins, enterotoxins - upregulation of CXC cytokines (IL-8, GRO-a, GCP2), IL-1B, IL-1 R-a, IL-4 - neutrophil
influx - phagocytosis by macrophages - transported to regional LNs, via portal circulation to liver; endotoxemia
with endothelial damage and thrombosis
Porcine Rectal Stricture - Salmonella typhimurium inf > thrombosis of cranial hemorrhoidal artery > ulcerative
proctitis > segmental rectal scarring & stricture & megacolon (per Thomson's) OR: Salmonella typhimurium
infection > damage & ischemia in areas supplied by pudendal & caudal mesenteric arteries > ulcerative proctitis
> segmental rectal scarring & stricture & megacolon (per J&K)
Mycobacterium bovis (TB) - intracellular survival (mycoside glycolipids form a barrier to phagosomal-lysosomal fusion and digestion
- cell wall glycolipids/waxes + peptidoglycan - adjuvant activity - recruitment/stimulation of macrophages - IL-12
--> IFN-g and IL-2 immune response (CD4+ lymphs) - delayed-type hypersensitivity response and granuloma
formation - impaired bacterial replication and spread - latent infection - reactivated with immune suppression
Mycobacterium avium ssp. ingestion - penetration of GI mucosa - taken up by macrophages
paratuberculosis
Mycobacterium avium, M. ingestion - granulomatous enteritis - hepatitis - other sites
genovense
Mycobacterium leprae Lepromatous form - no CMI
Tuberculoid form - vigorous CMI
Intermediate form - intermediate CMI
Clostridial Necrotizing Hepatitis Bacillary Hemoglobinuria (Red Water) - Dormant Clostridium haemolyticum spores in Kupffer cells > hepatic injury
from Fasciola hepatica migration > ↓ oxygen tension > spore germination > Phospholipase C toxin prod >
hepatocellular necrosis & IV hemolysis > icterus, hemoglobinemia, & hemoglobinuria
Black Dz (Infectious Necrotic Hepatitis) - Dormant Clostridium novyi (usually Type B) spores in liver> hepatic
injury from Fasciola hepatica migration > ↓ oxygen tension > spore germination > toxin prod > hepatocellular
necrosis
Clostridium chauvoei myositis Ingestion of spores of Clostridium chauvoei > deposition in muscle > trauma or transient ischemia to muscle >
(bovine) - Blackleg anaerobic environment > growth of latent spores > secretion of cytolytic exotoxins (lecithinases, hemolysin,
deoxyribonuclease, hyaluronidase) > necrosis of endothelium and myofibers
Clostridium septicum myositis wound infection - innoculation of bacteria into tissues - bacterial proliferation and toxin production
(equine)
Clostridium septicum ingestion of frozen foods containing spores - exotoxin evolution - exotoxemia
abomasitis (Braxy)
Clostridium perfringens (Type A proliferation of bacteria - elaboration of alpha toxin - mucosal necrosis and enterotoxemia; prediposed to by
- alpha toxin; type B - beta antibiotic administration, dietary chages
toxin)
Clostridium difficile (Types A, B,
C, D)
Subacute Clostridium exposure - intestinal epithelial necrosis + secretory component?; secretion of CPA and CPB2 - uncertain of
perfringens type A (CPA, CPB2, involvement in pathogenesis (CPB2 is expressed in 90% of cases); some strains produce CPE, associated with
CPE toxins?) similar lesions
Clostridium perfringens type C - exposure - Clostridial attachment to apical villus intestinal epithelium - desquamation of epithelium - infiltration of
beta toxin (CPB) basement membrane/lamina propria - necrosis (secretion of CPB toxin) - toxemia
Clostridium perfringens type D lambs on good-quality feed - proliferation of bacteria - elaboration of epsilon toxin - absorption of epsilon toxin
(epsilon toxin) (Pulpy Kidney into bloodstream - endothelial injury and edema
Disease)
Clostridial Enterotoxemia - Lambs - Fed on lush pasture or high grain diet > Clostridium perfringens Type D intestinal overgrowth > epsilon
Focal Symmetric toxin activated by trypsin > endothelial damage > ↑ vascular permeability & edema > focal brain hypoxia &
Encephalomalacia necrosis
Nigropallidal encephalomalacia in horses - Centaurea solstitialis (Yellow star thistle) OR Centaurea repens
(Russian knapweed) chronic ingestion (repin, a sesquiterpene lactone) > gluthatione depletion > increase of
reactive oxygen species (ROS) > bilaterally symmetric necrosis of the globus pallidus and substantia nigra
Clostridium piliformis infection via gastrointestinal system - systemic infection of liver, heart; associated with stress
C. difficile-associated per os or parenteral administration of narrow-spectrum antibiotic with antibacterial activity against Gram-positive
Antibiotic-induced bacteria (esp. with penicillin/bacitracin/ampicillin (excreted in bile) (normal gut flora are G+ Lactobacillus and
dysbacteriosis (Guinea Pigs) streptococci))  disruption of gut microflora  decrease in cultivable Gram-positive bacteria within 12 hr  up to
a 10,000,000-fold increase in Gram-negative bacteria (high incidence of bacteremia due to Escherichia coli has
also been observed in treated animals) and enterotoxigenic C. difficile
C. difficile-associated narrow-spectrum antibiotic (vancomycin, lincomycin, clindamycin, ampicillin, erythromycin, cephalosporins,
Antibiotic-induced gentamicin, penicillin)  loss of Gram-negative aerobic bacteria or other clostridia?  overgrowth with C. difficile
dysbacteriosis (hamsters)  elaboration of toxin  acute colitis, diarrhea, and death; may occur as an endogenous infection (organism has
been isolated from the intestinal tract of normal hamsters)
Botulism Exotoxicosis zinc-binding metalloprotease - cleaves specific proteins on synaptic vesicles - prevents release of acetylcholine
from vesicles at nerve terminals - flaccid paralysis
Tetanus Exotoxicosis wound - innoculation of bacteria into tissue - proliferation and death of bacteria - production of toxin
Tetanospasmin - absorbed by local motor nerves zinc-binding metalloprotease - cleaves synaptobrevin on
synaptic vesicles - inhibition of glycine, GABA release by inhibitory neurons ("Renshaw cells") - extensor spasm,
hyperesthesia
Hepatic Damaged rumenal mucosa > bacterial invasion > spread to liver via portal vein > hepatic necrosis
Fusobacteriosis/Actinomycosis
Fusobacterium necrophorum abrasion/trauma - bacterial colonization - bacterial toxin production - necrosis
Laryngitis
Contagious Foot Rot epidermal maceration > invasion of F. necrophorum > induction of interdigital dermatitis > secondary infection
with B. nodusus > necrosuppurative digital dermatitis +/- extension to underlying tissues with osteomyelitis,
tenosynovitis, and arthritis
Erysipelothrix rhusiopathiae septicemia > dermal vasculitis, thrombosis, & necrosis > cutaneous infarct
Strep equi ssp. equi (Lancefield virulence factors:
group C streptococcus) - hyaluronic acid capsule - mediates binding of bactera to host cells, resistance to phagocytosis
- M protein and a second cell wall constituent - bind fibrinogen, prevent deposition of C3 - block opsonization
- peptidoglycan - activates complement by alternate pathway - neutrophil chemotaxis
- streptolysin, other cytotoxin? - necrosis of neutrophils
Equine Pleuritis
Grain overload
Purpura Hemorhagica
Atrophic Rhinitis
Bordetella bronchiseptica
Lawsonia intracellaris
Rhodococcus equi
Burkholderia mallei
Burkholderia pseudomallei
Histophilus somni
Mannheimia haemolytica
Pasteurella multocida
Mycoplasma bovis
Mycoplasma mycoides
mycoides small colony type
(Contagious Bovine
Pleuropneumonia)
Corynebacterium bovis
Brachyspira hyodysenteriae
Staphylococcus aureus
(primates)
Edwardsiella ictaluri (Hole in
the Head Disease)
Listeria Monocytogenes
Corynebacterium
pseudotuberculosis
Infectious Disease (Viral)
Cerebellar hypoplasia, viral
Streptococcus equi ssp. Zooepidemicus, S. equi ssp. equi, Actinobacillus suis-like bacteria, other streptococci,
Pasteurella spp., Bordetella bronchiseptica, and E. coli, Bacteroides, and Fusobacterium; Mycoplasma felis
appears to result from aspiration (mixed infection, often unilateral); risk factors include: transportation with held
elevated (aspiration of tracheal pool of bacteria); generat anesthesia; stress; viral infection
sudden change to highly fermentable diet - growth of Gram-positive bacteria (Strep bovis, Lactobacillus spp.) -
evolution of lactic acid – rumenal acidosis (pH<5.5) – systemic acidosis; increased evolution of dissociated fatty
acids - ruminal atony - increased osmolality of rumen content - dehydration (osmotic effect)
Streptococcus equi equi Ag/Ab complexes. Ag/ab complex vasculitis.
Bordetella bronchiseptica inf allows Pasteurella multocida inf > Type A & D toxin prod > degen of osteoblasts &
chondroblasts > turbinate bone resorption (osteopenia)
intracellular pathogen with heat-sensitive gene expression: first wave - filamentous hemagglutinin, pertactin,
fimbriae (adhesion); second wave - genes regulating motility, iron scavenging, urease and phosphatase activity
virulence factors: adenylate cyclase toxin (RTX toxin) - pore former allows entry of adenlyate cyclase component -
increased cAMP - impaired leukocyte phagocytosis, oxidative burst; lipooligosaccharide - endotoxin activity;
peptidoglycan-derived tracheal cytotoxin - induces cells to produce NO - induces ciliostasis and apoptosis of
ciliated epithelium
receptor-ligand-mediated invasion of enterocytes  bacteria-induced stimulation of intestinal crypt epithelial cells
of small intestine (largely ileum) - necrosis of proliferating crypt cells with hemorrhage - attraction of
macrophages; induces immune suppression - reduction in CD8+ T cells and B cells; infection of macrophages -
secretion of TNF-a - vascular permeability and hemorrhage
survives engulfment by macrophages (prevention of phaosome/lysosomal fusion - pyogranulomatous
inflammatory response (cytokine secretion by infected macrophages?); clearance of infection requires:
- CD4+ T-cells - produce IFN-g - activate macrophages to produce bacteriocidal products
- CD8+ T-cells - induce lysis of infected macrophages
- opsonization of bacteria - optimized macrophage killing
organisms traverse pharyngeal mucosa, and perhaps intestinal mucosa - conveyed to lungs where lesions almost
always occur -hematogenous spread is believed to result in nasal, cutaneous, and lymph node lesions
bacterim survives in macrophage phagolysosomes - elicits a granulomatous and suppurative response
virulence factors: iron-scavenging malleobactin; secreted proteases (degrade host tissues); capsular
polysaccharide; resistance to phagocyte-mediated killing; LPS/endotoxin-derived polysaccharide - serum
resistance
- predisposed to by impaired pulmonary defenses (viral infection, stress, temp fluctuations, noxious gases)
- proteins that bind Fc Ab component - prevent complement activation
- Lipooligosaccharide - proinflammatory
- transferrin-binding protein
- vasculitis may be mediated by endothelial apoptosis
- facultative intracellular pathogen (monocytes; impairs phagocytic actions of macrophages, neutrophils, induces
neutrophil apoptosis, macrophage degeneration)
- predisposed to by impaired pulmonary defenses (viral infection, stress, temp fluctuations, noxious gases)
- leukotoxin (CD18-mediated pore-former)
- LPS - proinflammatory, procoagulant, complement activation
- capsular polysaccharide (resistance to phagocytosis and complement-mediated killing)
- transferrin-binding proteins A and B
- O-sialoglycoprotease
- neuraminidase
- AgG1-specific protease
- outer membrane proteins
- fimbriae
- predisposed to by impaired pulmonary defenses (viral infection, stress, temp fluctuations, noxious gases)
- antiphagocytic capsule
- neuraminidase activity
- induces apoptosis of lymphocytes
- suppression of lymphocyte responses to mitogens
- impaired neutrophil activation
- high frequency variation in expression of surface lipoproteins - evasion of humoral response
- galactan in mucus capsule induces necrosis, thrombosis, inflammation
Primarily occurs in athymic nude mice (immunocompetent mice may have subclinical infection) > hyperplastic
dermatitis
cytotoxic hemolysin is primary virulence factor; acts synergistically with anaerobic colonic microflora
cutaneous injury and innoculation - cellulitis - bacteremia - endocarditis/visceral showering - secondary immune
complex glomerulonephritis
multifocal cutaneous ulceration 2o to thrombosis; septicemic lesions in other organs;
In utero viral inf > inf & necrosis of cerebellar external germinal cells > defective Purkinje cell localization &
maturation > cerebellar hypoplasia
Bovine- in utero infection of Bovine Pestivirus (BVD), Akabane virus;
Cat- Feline panleukopenia virus (in utero);
Sheep- Border disease (Pestivirus),Cache valley fever virus;
Dog- Segmental hypoplasia - canine herpes virus, canine Parvo virus;
Pig- Hog cholera virus (Pestivirus)
Goat- Cache valley fever virus
Birds- Fowl glioma- inducing virus (avian leucosis virus group A)
Hydranencephaly/Porencephaly Bluetongue or Border Disease Virus In utero viral inf around 40-75 days gestation > inf & necrosis of undiff
, viral
Retroviruses
Retroviral pathogenicity
Equine Lentivirus (EIA)
Ovine/caprine Lentivirus
(Maedi/visna virus)
Caprine Arthritis/Encephalitis infection - viremia - insufficient HI/CMI - latency (months-years) in monocytes - activation of latent provirus by
Virus (Caprine Lentivirus)
Feline Immunodeficiency Virus infection/replication in CD4+Th cells, macrophages, astrocytes, microglia - chronic viremia - progressive
(Retrovirus - Lentivirus)
Feline leukemia virus (feline
gammaretrovirus-A/B)
Enzootic Bovine Leukosis -
Bovine Leukemia Virus
Ovine pulmonary
adenocarcinoma virus
(Jaagsiekte sheep retrovirus)
(betaretrovirus)
Avian retrovirus
(alpharetrovirus – Type C
oncornavirus) - Lymphoid
Leukosis
Avian retrovirus
(alpharetrovirus – Type C
oncornavirus) -
Erythroblastosis/Myeloblastosis
Parvoviruses
Parvoviral enteritis
Canine parvovirus-2
Feline panleukopenia virus
(feline parvovirus)
Aleutian Mink Disease
Coronaviruses
Coronaviral/Rotaviral enteritis selective destruction of mature villus cells - villus atrophy - malabsorption - diarrhea
Bovine enteric coronavirus
Endogenous mutant of Feline infection of epithelium of upper respiratory tract/intestine, regional lymph nodes - spontaneous mutation of FeCV?
enteric coronavirus
Infectious Bronchitis virus
(coronavirus)
Bovine Respiratory Coronavirus virus replicates in upper respiratory tract, rarely lungs
Orbiviruses
Bluetongue (orbivirus)
African Horse Sickness virus
(Equine Orbivirus - Reovirus)
Pestiviruses
Persistently Infected BVDV
BVDV enteritis - Mucosal
Disease
Acute BVDV infection
Acute Lethal BVDV (Type 2
Bovine pestivirus)
Thrombocytopenic BVDV
cerebral subventricular cells > cerebral cavitation
Receptor-mediated entry into target cells  viral genome undergoes reverse transcription (RNA DNA) 
1) In quiescent cells, may remain in cytoplasm
2) In actively dividing cells, may enter nucleus  integrated into host genome
a) proviral genome may remain untranscribed for months-years
b) proviral genome may be transcribed, producing infectious virus that causes membrane blebbing and rupture
(cell death)
c) proviral genome may contain viral oncogenes (v-Onc)  uncontrolled cell proliferation (acute-transforming
viruses)
d) proviral genome may insert near a host protooncogene  insertional mutagenesis (viral promoters cause
overexpression of cell protooncogene product)
Virus adsorbed on erythrocytes > IgM, IgG attachment to virus > complement activation > hemolysis; bone
marrow hyperplasia and then atrophy; ag-ab membranous glomerulonephritis; virus within macrophage
cytoplasm (ISH)
infection - viremia - infection of choroid plexus epithelium, fibroblasts, endothelial cells, monocytes - insufficient
HI/CMI - latency (months-years) in monocytes - activation of latent provirus by maturation into macrophages -
immunopathology due to persistent viral antigen; infection of alveolar macrophages - proinflammatory cytokines -
recruitment and activation of leukocytes - fibrosis, smooth muscle hyperplasia
maturation into macrophages - immunopathology due to persistent viral antigen
impairment of CMI due to reduced CD4+ cells - opportunistic infection
infection - local lymphoid replication - transient viremia - viral replication in lymphoid tissues, marrow - persistent
viremia - extensive infection of marrow, GI tract, salivary glands, bladder, respiratory tract
immne suppression may relate to p15E envelope protein
Enzootic Bovine Leukosis - infection of B-cells - expression of Tax and Rex regulatory gene proteins - B-cell
lymphoma
- prolonged latency (2 yrs); disease more likely in certain breeds; B204unknown mechanism of oncogenesis;
envelop protein is sufficient to induce similar tumors in immunosufficient mice
in B-cells, provirus integrates closely to host c-myc oncogene - viral replication triggers cell replication; provirus
genome may contain c-onc proto-oncogene - generate oncoproteins - stimulate cell transformation (fast-
transforming strains)
provirus integrates closely to host c-erbB oncogene - viral replication triggers cell replication
Virus inf of crypt epith cells during S/G2 cell cycle phase > utilize host cell DNA polymerase to replicate > necrosis
oral infection - viremia - replication in thymus, tonsils, retropharyngeal and mesenteric LNs, spleen - infection of
intestinal crypt epithelium (6d)
replication in oropharyngeal lymphoid tissues - viremia - infection of lymph nodes, spleen, thymus, bone marrow,
intestinal crypts (other rapidly-dividing cell types)
Parvoviral inf of lymphocytes >viral release > immune complex deposition in vessels, glomeruli, & other tissues >
plasmacytic vasculitis, GN, splenomegaly/hepatomegaly, & hypergammaglobulinemia
infection of intestinal epithelium (fascilitated by digestive enzymes - trypsin) - villus atrophy - malabsorptive
diarrhea; lymphoid infection (mesenteric LNs) - lymphoid depletion; rarely infects lungs
- dissemination within phagocytes - immune response - antigen-antibody complex formation - immun complex
deposition within blood vessels - complement activation - C3b production - neutrophil chemotaxis -
granulomatous-pyogranulomatous vasculitis
- Effusive form - lack of CMI, primarily humoral response > viremia > non-neutralizing antibodies deposited in
vessel walls > fibrinonecrotic peritonitis & vasculitis (effusive form)
- Noneffusive form - Coronaviral inf of møs > weak cell-mediated immune response > virus persists in møs >
pyogranulomatous inflam (non-effusive form)
primary infection of respiratory mucosal epithelium; some nephrotropic strains
Culicoides (midge, gnat) bites sheep > hematopoietic cell viral replication > viremia > widespread endothelial cell
viral replication & damage > hemorrhage, edema, thrombosis, & infarction - Hemorrhage at the Base of the
Pulmonary Artery; Rumenal Pillar Hemorrhage & Necrosis
virus replicates in lymph nodes, spleen, thymus, pharyngeal mucosa - infection of capillary endothelium
Type 1 Noncytopathic Bovine Viral Diarrhea virus (bovine pestivirus) - immunotolerant animals with persistent
infection in utero (<100d gestation) with noncytopathic infection
In utero inf w/ noncytopathic BVD virus (less than 4 months)> develop immunotolerance & persistent inf >
postnatal inf w/ cytopathic strain > inf epith > mucosal dz w/ necrotizing stomatitis, esophagitis, enteritis, etc.
Type 1 Noncytopathic Bovine pestivirus infection - replication in epithelium/palatine tonsils - viremia - infection of
lymphocytes and monocytes - necrosis of epithelia/leukocytes, limited submucosal vasculitis
virulent Type 2 BVDV strain
Type 2 Bovine pestivirus infection - reduced circulating platelets and impaired function
"Hairy Shakers"
Feline Herpesvirus-1
(varicellovirus-
alphaherpesvirus)
Herpesviruses
Canine Herpesvirus-1
(varicellovirus-
alphaherpesvirus)
Porcine herpesvirus-1
(varicellovirus-
alphaherpesvirus)
Equine Herpesvirus-1 and –4
(varicellovirus-
alphaherpesvirus)
Malignant Catarrhal Fever
Africa - Alcephaline
herpesvirus-1 (Rhadinovirus-
Gammaherpesvirus)
Other - Ovine Herpesvirus-2
(Rhadinovirus-
Gammaherpesvirus)
bovine herpesvirus-1
(varicellovirus-
alphaherpesvirus)
Gallid herpesvirus-2
(alphaherpesvirus) - Marek's
Disease
Herpesvirus simiae/Simian
Herpesvirus B (Cercopithecine
herpesvirus-1)
Elephant Endotheliotropic
Herpesviruses (EEHV 1-3,
probosciviruses,
betaherpesviruses)
Paramyxoviruses
Canine Distemper Virus
(Morbillivirus - paramyxovirus)
infection prior to 6 months of
age
Canine Parainfluenzavirus-2
(Rubulovirus - Paramyxovirus)
Hendra Virus (Henipahvirus -
Paramyxovirus)
Rinderpest Virus (Morbillivirus -
Paramyxovirus)
Bovine/Ovine Respiratory
Syncytial Viruses (Bovine
Pneumovirus - Paramyxovirus)
bovine parainfluenza virus-3
(paramyxovirus - respirovirus) alveolar macrophages (impaired phagocytosis/oxidative killing, induce contact-mediated suppression of
Avian Paramyxovirus type 1
(Avulovirus - Paramyxovirus) - Velogenic strains are highly pathogenic, mesogenic less pathogenic, lentigenic low pathogenicity; Viscerotropic
velogenic Newcastle DV
Rhabdoviruses
Rabies (Rhabdovirus-
Lyssavirus)
Orthomyxoviruses
Equine Influenza Virus
(Orthomyxovirus type A
subtype H3N8)
Swine influenza virus
(Orthomyxovirus Type A)
Avian Influenza virus (Type A Hemaggliutinin mediates virus interactions with cell receptors, with later cleavage mediating fusion of cell
orthomyxovirus)
Adenoviruses
Canine adenovirus type I
(Mastadenovirus)
Equine adenovirus A (Equine
Adenovirus-1; Mastadenovirus)
Bronchopneumonia
persistent congenital infection of lambs with Border disease virus (ovine pestivirus) - fetal malformations (CNS
hypomyelinogenesis, hydranencephaly/ porencephaly, skeletal immaturity, decreased secondary hair follicles)
viral replication in nasal mucosa, tonsils, pharynx - cytolytic infections of mucosal epithelial cells and
establishment of latency in the trigeminal ganglion, optic nerve, olfactory bulb, and cornea - reactivation of latent
infection is often of unknown cause, but may be triggered by corticosteroid therapy, stresses associated with
environmental changes, or parturition; virus replicates optimally at temperatures less than 37oC; thus, most
infections are limited to the upper respiratory tract and conjunctiva; neonates - subnormal temperatures - viremia
- infection of vascular endothelium, parenchymal organs
viral replication in nasal mucosa, tonsils, pharynx - subnormal temperatures - viremia - infection of vascular
endothelium, parenchymal organs
virus replicates in mucus membranes of nasopharynx, tonsils - spread to regional LNs, CNS via CN axons - viremia
- infection of multiple organs; transplacental infection; latency
viral replication in nasopharynx and associated lymphoid tissues - endothelial infection
contact with infected host species (Wildebeest, sheep) - probably respiratory infection - cell-associated viremia -
possible immune-mediated disease
virus replicates in upper respiratory tract - spread via nasolacrimal ducts
infection of nervous system, lymphocytes (primary) and other tissues
bite by infected monkey - local inflammation and vesicle formation, necrosis - invasion of CNS by peripheral
nerves
Endotheliotropism  ascites, widespread visceral edema, petechiae, and capillary damage, grossly visible renal
medullary hemorrhage, a tropism for larger veins and arteries in various tissues, relatively high density of renal
herpetic inclusions, and involvement of the retinal vessels
- less selective organ tropism, and this may confer a higher degree of virulence for EEHV3
infection depends on haemagglutinin (mediates viral attachment to host cell) and fusion glycoproteins
- (penetration of host cell, fusion of infected and uninfected cells); replication in bronchial LNS, tonsils - leukocyte-
mediated viremia - inadequate CMI/HI - infection of mononuclear cells of lymphatic, alimentary, respiratory
systems, nervous systems - infection of alimentary, respiratory, urogenital, endocrine systems, foot pads, glial
cells, ependymal cells, neurons; destruction of ameloblasts
impaired mucociliar clearance; increased bronchoconstrictive response to agonists such as histamine
fruit bat reservoir - vascular tropism in lungs - spread of virus by infected macrophages to vasculature of brain,
liver, kidneys, liver, myocardium, spleen
respiratory infection - replication in tonsils and lymph nodes - leukocyte-mediated viremia - dissemination to
spleen, bone marrow, lymphoid tissues, epithelium of respiratory and alimentary tracts
virus replicates in respiratory epithelium, causes local necrosis
infection + stress - replicates in macrophages and alveolar epithelium - impaired mucociliary function, damage to
lymphocyte responses) - impaired antibacterial defenses
viral replication in respiratory tract - primary viremia - multiplication in parenchymal organs - secondary viremia;
strains produce respiratory disease, enteric disease, Neurotropic strains produce nervous and respiratory disease
bite - virus infects in muscle at site of wound (via nicotinic ACh receptor?) and multiplies - infects sensory neurons
- axonal transport to CNS (protected from immune system) - multiplies in CNS - travels down peripheral nerves -
infects salivary gland, cornea, tonsil
infection of upper and lower airway epithelium; Hemaggliutinin mediates virus interactions with cell receptors,
with later cleavage mediating fusion of cell membrane and virus envelope (Ab protect against infection);
Neuraminidase mediates virus release from infected cells (Ab prevent disease/contagion)
infection of upper and lower airway epithelium; Hemaggliutinin mediates virus interactions with cell receptors,
with later cleavage mediating fusion of cell membrane and virus envelope (Ab protect against infection);
Neuraminidase mediates virus release from infected cells (Ab prevent disease/contagion)
membrane and virus envelope (Ab protect against infection); Neuraminidase mediates virus release from infected
cells (Ab prevent disease/contagion)
replication in tonsils, Peyer's patches - localization and replication in liver and kidney
Uveitis - Type 3 (immune complex) hypersensitivity to persistent viral antigen - complement activation -
neutrophil attraction and injury
small white foci, mainly in Arabian foals with congenital combined immunodeficiency
Bovine Adenovirus
Togaviruses
Eastern Equine Encephalitis;
Western Equine Encephalitis; viremia - infection of many tissues (including brain, via exposed nerve endings or neuromuscular junctions)
Venezuelan Equine Encephalitis
(Togaviruses - Alphaviruses)
Arteriviruses
Equine Arteritis Virus
(Arterivirus)
Porcine reproductive and
respiratory syndrome
Picornaviruses
Foot and Mouth Disease Virus
(Bovine Aphthovirus -
Picornavirus)
Swine vesicular diseas virus
(Enterovirus - picornavirus)
Avian encephalomyelitis virus
(hepatovirus - picornavirus)
Flaviviruses
Ovine Flavivirus (Louping Ill)
Poxviruses
Lumpy Skin Disease Virus
(Capripoxvirus)
Sheeppox (Capripoxvirus)
Goatpox (Capripoxvirus)
Orf Virus (Parapoxvirus)
Swinepox virus (Suipoxivirus) Transmitted by sucking louse (Haematopinus suis) - skin trauma
Fowlpox viruses (avipoxvirus) entry via abrasions; carried by mosquitos
Myxoma virus (leporipoxvirus) - transmitted by biting insects; replicates in epithelial cells, fibromas in SQ and dermis
Myxomatosis, Shopes Fibroma
Asfarviruses
Porcine Asfarvirus
Circoviruses
Porcine circovirus-2
Beak and feather disease virus infection of cells of immune system, feather follicular epithelium
(circovirus)
Chicken anemia virus
(Gyrovirus - Circovirus)
Birnaviruses
Infectious bursal disease virus infection (oral, respiratory, conjunctival) - infection of lymphohistiocytic cells in liver, jejunum, duodenum, cecum -
(avibirnavirus serotype 1)
Caliciviruses
Rabbit hemorrhagic disease
virus and European Brown Hare
Syndrome Virus (Calicivirus -
Lagovirus)
Papillomaviruses
Equine Sarcoid (BPV-1/2)
Infectious (Fungal)
Mycotic Rumenitis
Guttural Pouch Mycosis
Aspergillus fumigatus
Blastomyces dermatitidis
Histoplasma capsulatum
Cryptococcus neoformans var
neoformans
Cryptococcus neoformans var
gatii
Candida albicans
may predispose to bacterial pneumonia by injuring ciliate epithelium, impairing alveolar macrophages
innoculation by an infected insect (mosquito) - primary viral replication in lymph nodes - primary and secondary
repiratory infection - replication in pulmonary macrophages - replication in bronchial LNs - viremia - infection of
endothelial cells - necrosis
presumed mucosal portal of entry  virus replication in local macrophages  transient viremia  dissemination
of phagocytic cells to the lungs and other organs, such as the thymus, liver (Kupffer cells), spleen, all lymph
nodes, and intestine  known to induce apoptosis as a mechanism of cell destruction and persistent infection as
a mechanism of dissemination
viral replication in pharynx - viremia - infection of epithelium via dermal papilla; vesicle formation secondary to
lysis fo infected cells and release of cytoplasm
infection of epithelium - viremia - generalized infection of lymphoid tissues
ingestion - infection of duodenum - viremia - infection of visceral organs, brain
transmitted by Ixodes ricinus - biphasic fever - progressive nervous dysfunction
spread by biting flies - percutaneous infection - systemic spread (endothelium, keratinocytes, fibrocytes, skeletal
muscle, macrophages, pericytes, glandular epithelium) - thrombosis-infarction-
infection - viremia - dissemination of virus to skin, lymph nodes, spleen, kidney, lungs; vasculitis 2o to immune
complex deposition?
infection - viremia - dissemination of virus to skin, lymph nodes, spleen, kidney, lungs
infection of cutaneous abrasions
oronasal infection - viral replication in pharynx, tonsils, lymph nodes - viremia - infection of lymphoreticular
system within marrow, lymph nodes, lungs, kidneys, liver
initial infection - viremia - infection of multiple organs
infection of day-old chicks - viremia - infection of T-cells in Thymic cortex and bursa, hematopoitic cells of bone
marrow - aplastic anemia and immune suppression
infection of B-cells in Bursa of Fabricius - Viremia - infection of thymus, Harderian gland, spleen - depletion of
Bursa - impaired immune response
oronasal infection - infection of mononuclear phagocytes
transformation activity of the virus is due to the binding of the E5 to the platelet-derived growth factor β receptor
(PDGFβ-r)  downstream activation of PI3K–AKT–cyclin D3
Aspergillus fumigatus, Candida albicans, Absidia corymbifera, Rhizomucor (Mucor) pusillus; Mortierella spp.
Grain overload > rumenal acidosis > mucosal damage > opportunistic fungal inf > vasculitis > ischemia &
mucosal ulceration
Aspergillus nidulans guttural pouch infection> erosion of int. carotid artery > hemorrhage
uncertain whether disease relates to exposure dose or impaired nasal defenses; immune suppression is only
rarely reported; Antibiotics?
inhalation of mycelial forms - convert into yeast forms - proliferate in lungs - disseminated via blood and
lymphatic vessels; Th1 immune responses associated with protection in mouse models
- BAD-1 - surface protein - mediates adhesion to host cells, may modulate inflammatory response
- cell wall polysaccharide a-glucan - may protect against killing by macrophages
yeast invades tissues, causes necrosis, replicates in macrophages
inhalation of basidiospores (yeast cells) from contaminated dust - nasal disease - infection may progress by local
spread to brain, aspiration to lung, or hematogenous spread to brain, eyes, lymph nodes, skin and other organs;
disease only occurs with immune suppression
- thick capsule - glucuronoxylomannan, other mannose-rich polysaccharides - impairs phagocytosis, activates
complement, and may suppress T cell responses
- ability to synthesize melanin - may scavenge oxygen radicals produced by activated macrophages, and
modulate the host immunoinflammatory response
- secretion of eicosanoids and mannose protein that modulate immune and inflammatory responses
- production of superoxide dismutase and laccase that augment resistance to oxidative killing
underlying debility/immunodeficiency; antibiotic therapy (destruction of normal oropharyngeal flora); elevated
blood glucose
Coccidioides immitis
Microsporum canis and
Trichophyton
Infectious (Ectoparasites)
Sarcoptes scabei
Demodex canis
Ctenocephalides felis
(common)
Ctenocephalides canis
Infectious (Nematodes)
Strongylus vulgaris
Toxocara cati (usually large
burdens)
Toxascaris leonina
entrapped larval Toxocara cati larval migration in stomach wall - tissue reaction to antigens in larval feces, sheath, saliva
Strongyloides stercoralis
Eucoleus aerophilus
Aelurostrongylus abstrusis
Oslerus rostratus
Spirocerca lupi
Oslerus osleri (upper)
Crenosoma vulpis
Angiostrongylus vasorum
Filaroides hirthi (lower)
Andersonstrongylus milksi
Parascaris equorum
Strongyloides westerii
Oxyuris equi
Ostertagia ostertagia
Teladorsagia circumcincta
Oesophagostomum radiatum third stage larvae are ingested, penetrate deeply into small intestinal wall, excyst, molt to fourth stage - mature
Oesophagostomum
columbianum
Oesophagostomum dentatum
Bunostomum spp.
Trichostrongylus spp.
Nematodirus spp.
Inhalation of airborne arthroconidia is usual route of infection; local inoculation occasionally causes a cutaneous
lesion that does not usually progress to systemic infection
infection of stratum corneum and hairs/follicles
intrepidermal migration - excretion - hypersensitivity
mites proliferate - follicular dilation and hyperkeratosis - follicular plugging - follicular rupture - furunculosis
reaction (foreign body reaction against keratin)
infestation - feeding injects proteolytic enzymes and histamine-like substances - immediate and delayed-type
hypersensitivity responses
Ingestion of L3 larvae of Strongylus vulgaris > larvae enter wall of cecum and colon and molt to L4 larvae >
penetrate arterioles > migrate up the vessel along the intima > localize in cranial mesenteric artery and its
branches along the aorta > arteritis, thrombosis + aneurysm > + emboli to small and large intestine > intestinal
infarction and abdominal pain (colic).
Toxocara - infection by ingestion (milk, environment), horizontal transmission - infective larvae penetrate
intestine - liver (portal bloodstream) - lungs (caudal vena cava) - larval development in alveoli - coughed and
swallowed - development of adults - ova passed in feces
Toxascaris - ingestion of intermediate host - no hepatopulmonary migration
both free-living and parasitic forms; larvae enter host by skin penetration, transplacentally or (rarely) ingestion -
migrate into bloodstream - lung airways - coughed and swallowed - intestinal tract
parasitizes the trachea and bronchi of wild canids, domestic dogs, and occasionally cats; eggs are laid in the
airways, move with mucus to the pharynx, are swallowed and passed in the feces - larvae undergo initial
development in the egg, and then progress to the infective stage within earthworms, which are a required
intermediate host - Eggs also hatch in about 40 days under suitable environmental conditions, but the resulting
larvae are apparently not infective - After ingestion of the earthworm, the larvae reach the lungs in ~1 week and
are mature in the trachea in about 25 days
adults (slender and up to 1 cm long) live in terminal bronchioles and alveolar ducts - eggs form nodular deposits
in alveoli, where they embryonate and hatch to give first-stage larvae - larvae reach the airways and are passed
in the feces - Snails and slugs are intermediate hosts, while birds, rodents, frogs, and lizards are paratenic
(transport) hosts - life cycle can be completed if a cat eats either an intermediate host or a paratenic host -
Infective larvae migrate to the lungs and reach maturity ~4-6 weeks after ingestion of the third-stage larvae
viviparous parasite; death of parasite provokes intense suppuration, mineralization, fibrosis
stomach - aorta - esophagus - discharge ova into esophageal lumen
acquired from the dam through grooming or regurgitative feeding; thin-walled embryonated eggs are coughed up
and swallowed and many hatch before being passed as infective larvae in the feces à do not require an
intermediate host à first-stage larvae of O. osleri are immediately infective, and pups are infected by ingestion of
larvae in the saliva, tracheobronchial secretions, or feces of their dams à Larvae migrate from the gut through the
blood to the lung à develop into fifth-stage larvae by 5 weeks after infection, and tracheal nodules are detectable
at 10 weeks and well developed by 18 weeks
snails and slugs are intermediate hosts - Adult worms reside in bronchioles and small bronchi - After a prepatent
period of 18-21 days, adults produce larvae that are passed in the feces for about 8 months
Adults inhabit pulmonary arteries and right ventricle of dogs and foxes; eggs pass via the blood to the lungs,
where the larvae hatch, penetrate into alveoli, are coughed up and passed in the fecesà prepatent period is 38-57
days. Snails and slugs serve as intermediate hosts.
adults live in alveoli and respiratory bronchioles àhas a direct life cycle, and infective first-stage larvae are passed
in the feces; many infections are probably acquired from the dam
molluscan intermediate host has been proposed, but the life cycle is unknown
infection by ingestion (milk, environment), horizontal transmission - infective larvae penetrate intestine - liver
(portal bloodstream) - lungs (caudal vena cava) - larval development in alveoli - coughed and swallowed -
development of adults - ova passed in feces
administration of anthelmintics with large parasite burdens - death of large numbers of ascarids - impaction and
obstruction
both free-living and parasitic forms; larvae enter host by skin penetration, transplacentally or (rarely) ingestion -
migrate into bloodstream - lung airways - coughed and swallowed - intestinal tract
parasites inhabit lumen of distal colon/rectum - lay eggs on perineum
infection - enter gastric glands - lymphonodular hyperplasia, eosinophilic inflammation - induce mucus cell
hyperplasia and atrophy of Chief and parietal cells - maldigestion
in colon - either encyst in colonic wall and form mineralizing granulomas or mature into adults
infection of infective larvae by ingestion (milk, environment), horizontal transmission, dermal penetration -
migration to intestine - development of adults - ova passed in feces
direct life cycle - thrid stage larvae are rendered infective by abomasal pH - larvae burrow into crypts but do not
penetrate - crypt hyperplasia and paradoxical crypt atrophy - malabsorptive and protein-loss enteropathy
overwinter to become infective - fourth and fifth-stage larvae reside in deeper layers of mucosa - villus atrophy;
 rarely cause disease
Cooperia spp nematodes live between small intestinal villi - pressure necrosis
Dictyocaulus viviparus, D. third-stage larvae ingested - penetrate wall of intestine - migrate via lymphatics to mesenteric lymph nodes -
filariae molt to fourth-stage larvae - travel by way of lymph and blood to enter lungs about 7 days after infection - final
molt to fifth-stage larvae in bronchioles - adults develop in larger airways - eggs are embryonated when laid,
hatch rapidly - First-stage larvae are expelled from lung by coughing, are swallowed, and then passed in feces -
development to infective third-stage larvae occurs on ground over the next 5-7 days
Hemonchus contortus infection - enter gastric glands - emerge as adults - feed on blood through abomasal mucosa - severe anemia and
(barberpole worm) hypoproteinemia
Muelleria capillaris - Multiple Adults in nodular lesions in alveoli and rarely in bronchioles, but are usually not visible at necropsy - lay eggs -
1-20 mm diameter (usually 2-4 rapidly hatch - first-stage larvae are coughed up, swallowed, and passed in feces - intermediate hosts are various
mm) subpleural nodules in slugs and snails - infective stage is reached after 2 molts in intermediate host - sheep and goats swallow the
dorsal regions of caudal lobes intermediate hosts - larvae migrate to lungs, presumably via lymphatics, and break out into alveoli - infections are
Protostrongylus rufescens - acquired gradually, and large worm burdens are seldom observed in animals <6 months of age
2-4cm diameter angular firm,
tan nodules distributed
throughout lungs
Neostrongylus linearis - 1-
4mm red-violet or grey-pink
nodules in caudal lung
Cystocaulus creatus - 5-
20mm diameter dark firm
nodules in dorsocaudal lung;
brown-black hair-like worms
Ascaris suum (Roundworm) infection by ingestion (milk, environment), horizontal transmission - infective larvae penetrate intestine - liver
(portal bloodstream) - lungs (caudal vena cava) - larval development in alveoli - coughed and swallowed -
development of adults - ova passed in feces
Strongyloides spp. both free-living and parasitic forms; larvae enter host by skin penetration, transplacentally or (rarely) ingestion -
migrate into bloodstream - lung airways - coughed and swallowed - intestinal tract
Globocephalus spp. infection of infective larvae by ingestion (milk, environment), horizontal transmission, dermal penetration -
migration to intestine - development of adults - ova passed in feces
Macracanthorhynchus arthropod intermediate host; attach to wall of GI tract
hirudinaceus
Balisascaris procyonis ingestion of embryonated eggs  the larvae are released in the intestine and undergo aggressive somatic and
(aberrant migration) pulmonary migration  severe damage, particularly in the central nervous system, is attributed to the rapid
growth of the larvae, ability to migrate into the brain (resulting in extensive trauma in target areas), metabolic
wastes and enzymes elaborated by the parasite (may evoke a vigorous inflammatory response)

Trematodes
Alaria spp. paratenic hosts - frogs, snales, mice
Nanophyetus salmincola snail and fish as intermediate hosts
Paragonimus kellicoti first intermediate hosts are small aquatic snails; second intermediate host is a freshwater crab or crayfish -
crayfish is eaten by the definitive host - metacercariae are liberated in the intestine and migrate across the
peritoneal and pleural cavities to the lungs - passage through the pleura is marked by multiple small hemorrhages
and foci of eosinophilic and fibrinous pleuritis that heal as small umbilicated scars
Fascioloides magna, Fasciola aberrant parasite migration within liver
hepatica

Cestodes
Taenia pisiformis/taeniaformis attach to GI wall via anterior scolex - absorb nutrients via outer surface - compete with host for nutrients
Dipylidium caninum (flea
tapeworm)
Diphyllobothrium spp.
Mesocestoides spp.
Anaplocephala perfoliata
Paranoplocephala mamillana
Monezia spp
Taenia saginata
Cysticercosis (Cysticercus infected by contamination of food with cat feces  eggs of this tapeworm are ingested  migrate through the
fasciolaris, Taenia bowel and often encyst in the liver
taeniaformis)
Coenurus cerebralis CNS of the sheep is invaded by Coenurus cerebralis, the cystic larval stage, or metacestode, of the tapeworm
Taenia multiceps. ingestion of the larval stage by the carnivore (occurs when carnivore ingests raw, infected
sheep's brain or offal) - Taenia multiceps then lives in small intestine of carnivores - sheep get infected by
consuming herbage contaminated with onchospores or Taenia eggs - embryos then pass via the blood to the CNS
Hymenolepsis nana (“dwarf Direct or indirect (via arthropod IH) life cycle with cercocystis in villi – possible zoonosis
tapeworm”).

Infectious (Microparasites)
Cystoisospora spp.
Eimeria bovis, zuernii, leukarti,
arloingi, christenseni, Eimeria
nina-kohl-yakimovae
Isospora suis
Giardia lamblia
Cryptosporidium parvum
Neorickettsia helminthoeca
Entamoeba histolytica
Bovine Enteric Chlamydiosis
(Chlamydophilia psittaci)
Babesia bovis
Encephalitozoon cuniculi
Infectious (Other)
Ovine or bovine neurotropic
prion?
Kennel Cough
ingestion of sporulated oocyst (2 sporocysts containing 4 sporozoites) - sporozoites excyst - invade enterocytes -
merogony (asexual reproduction - schizont containing many merozoites) - rupture of host cell and reinvasion -
gametogony (sexual reproduction - female macrogametocyte fertilized by male microgametocyte) - oocyst
ruptures from host cell, passed in feces, sporulates
infection - attach to enterocyte microvilli - membrane damage - decreased absorption of
monosaccharides/disaccharides - bacterial fermentation - osmotic diarrhea
Protozoa displace microvilli - enclosed by surface cell membranes (not vacuolated - intracellular but
extracytoplasmic) -
ingestion of salmon containing infected fluke (Nanophyetus salmincola)
fecal-oral transmission; cell associations are mediated by adhesins; intracellular organism
chlamydia are endocytosed - multiply in epithelial cell apices - liberated into lamina propria
altered RBC glycocalyx - "stickier" RBCs - adhesion to capillary endothelium
Dwarf rabbits may be more susceptible; obligate intracellular Gram-positive microsporidian; persist for up to 6
weeks at RT, mature spore stage has coiled polar filament to inject sporoplasm; oral or respiratory infection 
spores pass via mononuclear cells into systemic circulation → high blood flow organs (liver, kidney, lung → brain ~
1 month); development of sporoblasts within cytoplasmic vacuole → xenoma → spores shed in urine
polymorphisms in PrP gene influence susceptibility; exposure to PrP-sc prion induces conformational change in
normal PrP - PrP-sc forms abnormal protein aggregates/polymers in brain
Canine Adenovirus-2 (Mastadenovirus)'+/- canine parainfluenzavirus (Rubulavirus - Paramyxovirus) '+/-Bordetella
bronchiseptica '+/- Canine Adenovirus-2 (Mastadenovirus) '+/- Canine Herpesvirus-1 (varicellovirus-
alphaherpesvirus) '+/- Canine Reovirus '+/- Mycoplasma spp.