VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su

GI Disease
Fetus/ Neonates ® very young | Juvenile ® young animal or immunocompromised | Any age ® non-specified
All Animals
Age group Agent Manifestation
Fetuses/Neonates Herpes Viremia
Multifocal necrosis of liver
Staph/ strep (chronic) Liver abscess
Juvenile Clostridium piliformes Tyzzer’s disease
Mf necrotizing hepatitis +/- colitis
Any age Mycobacterium tuberculosis (many Granulomas / hepatic granulomas
different causes)
Taenia spp. Immature cysticerci in horses, pigs, ruminants
Adult in SI od dogs
Tracks
Echinococcus granulosus Ruminant> pigs, horse, dog
Zoonotic Larval cysts
Echinococcus multilocularis Various rodents > aberrant IH can be all animals and
Zoonotic human
Cyanobacteria Ruminants> SA
Massive necrosis of liver
Congestion
Chronic liver disease
Pyrrolizidine alkaloid Pigs > horse
Cattle> Sm ruminants
Megalocytosis (stop mitosis and apoptosis)
Chronic hepatic fibrosis
Demarcated regenerative nodules
Dental plaque and caries (herbivores) Digestion of organic matrix and bacteria invasion
Paranasal sinus empyema
Periodontal disease and gingivitis Inflammation
Tooth absecess, loss, bacteremia
Vesicular stomatitis Ruminant, horse, pigs
Superficial stomatitis ® erosive and ulcerative

Small Animals
Age group Agent Manifestation
Fetus/Neonates Distemper Nervous signs
Enamel hypoplasia
Parvovirus Malabsorptive and exudative diarrhea
Fibrinonecrotic enteritis
No crypts
Parvo myocarditis
Cerebellar hypoplasia (cats)
Juvenile Canine Adenovirus-1 Multifocal necrosis of liver
Vasculitis (corneal edema)
Cystospora (coccidia) Fluid diarrhea yellow-mucoid
Giardia Intermittent diarrhea
Trichomonas fetus (cats) Abortion
Chronic LI diarrhea
E coli (dogs <2 yrs old) Histiocytic ulceratic colitis
Adult Neutrophilic cholangitis / feline May be a part of triaditis with concurrent extrahepatic
progressive lymphocytic cholangitis bile duct obstruction, IBD and pancreatitis in cats
Any age Leptospirosis interrogans Liver and kidney signs
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Zoonotic Cholestasis
Pre-hepatic jaundice
Interstitial nephritis
Acute hemolytic crisis
Xylitol toxicity Dogs
Massive necrosis of liver (Z3)
Acetaminophen toxicity Cat > ferret, dog
Z2 necrosis/ oxidative injury
Acute hepatic failure
Chronic copper hepatoxicity Liver cirrhosis (esp zone 3)
(COMMD1 gene mutation ® impaired Cu excretion in
bile)
Hemangiosarcoma Flat tumours, blood filled cavities
Eosinophilic granuloma complex Ulcerative stomatitis
Responsive to steroids
Squamous cell carcinoma Ulcerative stomatitis
Lymphoplasmacytic stomatitis/ Idiopathic
gingivitis
Candida/ Thursh Coagulative necrosis
Hookworm Exudative diarrhea
Protein loss and bleeding
Hemorrhagic enteritis
Ascarids (toxocar canis and toxcara cati Nutrient competition
Obstruction
Taenia taeniformis (cats) Nutrient competition
Diplydium caninum (dogs) Obstruction
Trichuris vulpis (dogs) Hemorrhagic typhilitis
Coronavirus Attneuated villus tip
4-6d to recover
CIP in cats ® wet and dry form (granulomas)
Camylobacter jejuni Possible mild enterocolitis?
Neoickettsia helminthoeca Transmitted by flukes ® salmon poisoning ® fever
Induced granulomas
Acute hemorrhagic diarrhea syndrome Causal stomach necrosis
- Clostridium type A? Melena
Histoplasma capsulalum Systemic granulomas (LN, liver etc)
IBD (multifactorial/ immune mediated) Lymphocytic and plasmocytic enteritis
Neoplasia Squamous cell carcinoma Common in cats mouth
Locally aggressive and infiltrate, slow to metastasize
Gastric adenocarcinoma Loss of rugal pattern
Aggressive
Lymphoma Most common GIT
Focal, segmental, diffused
T cell > B cell
Adenocarcinoma Stricture
Thickening of wall
Mesenchymal tumours Can be anywhere (LI> SI> Stomach)
Well demarcated
Rectal papillary adenoma Looks like polyp
Distal rectal mucosa
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Equine
Age group Agent Manifestation
Fetus/Neonates Rhodococcus equi Pyogranulomas in GIT, LN, lungs
Bronchopneumonia ® coughed up and swallowed in
large numbers
Rotavirus Undifferentiated diarrhea
Cryptosporidium Undifferentiated diarrhea
Strongyloides westeri Undifferentiated diarrhea
Actinobacillus equuli Abscesses throughout the body
Bacteremia
+/- Diarrhea with hemorrhage
Juvenile Lawsonia intracellularis Malabsorptive diarrhea
Thickened intestinal wall
Collision necrosis of enterocytes
Adult Salmonella typhimimurim Chronic ® button ulcers
Ulcerative typhlocolitis
Stricture

Duodenitis proximal jujunitis (5-10yr) Necrohemorrhagic enteritis

Unknown cause
Potomac horse fever Infected macrophage and enterocype
Colic
Watery diarrhea (chronic)
Cyasthastome Watery diarrhea
Flecks in dairrhea
Nodular eosinophilic colitis with intralesional nematode
(in deep mucosa)
Necrohemorrhagic typhlocolitis when L4 emerges
Strongylus vulgaris Endoarteritis of cranial mesenteric artery
(S edentatus is rare( Trhomboemboli ® aterial infarction of watershed areas
Anoplocephala perfoliate At ileocecal junction
­Risk of Spasmodic colic, ileal impaction, intussusception
(ileocecal or ceocolic)
Stomach bots: Gastrophilus intestinalis Incidental
and nasalis
Parascaris equorum Ill-thrift
Heavy burden can cause obstruction, perforation
NSAID intoxication Ischemic necrosis and ulceration
Any age Parvovirus Theiler’s disease ® dishrag liver, generalized zonal Z2
and Z3 to massive necrosis
Acute hepatic failure
Clostridium perfringens type C Occasionally in adults, usually in young
Beta toxin
Clostridium difficile Any age
A and B toxin
Salmonella typhimimurim Adults:
Chronic ® button ulcers
Ulcerative typhlocolitis
Stricture
Young:
Peracute foal diarrhea
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Ruminants
Age group Agent Manifestation
Fetus/Neonates ETEC* 1-3d
* = small ruminants EPEC Acute yellow/ white diarrhea
F5 fimbria

Clostridium perfringens type D Angiotoxin e-toxin that causes edema disease of small
ruminants
Pulpy kidney, petechia, encephalomalacia, edema
Clostridium perfringens type C Beta toxin
Necrosis of the endothelium
Rotavirus*/ corona virus Villus atrophy
Severe diarrhea
Cryptosporidium parvum* Intermittent diarrhea, malabsorptive
Watery, profuse
Villus atrophy
Coccidia* > 18d
Eimeria Scour with blood/ mucus
Fibrinohemorrhagic typhlocolitis
Nervous signs ® often die
In kid/ lamb SI ® mf proliferative enteritis (like lawsonia)
Persistent infection BVD Infected fetus at 30-120d of gestation
Mucosal disease BVD 4m to 2 years old
Severe diarrhea, dehydration, ulcers
Mutated or simultaneous strains of BVD virus
Adult Corynebcaterium pseudotuberculosis Caseous granulomas
(sm ruminant)
Fusobacterim necrophorum Liver abscess
Coagulative necrosis of liver
Truperella pyogenes Liver abscess
Classic BVDV Leukopenia
Oculonasal discharge
Severe acute BVD Severe ulcers
Enteritis and diarrhea
Lymphoid depletion
BVD - Thrombocytopenia Hemorrhagic syndrome with epistaxis, mucosal
hemorrhage, bloody diarrhea
Winter dysentery – bovine corona Green black bloody mucoid diarrhea
virus Spontaneous recovery <4d
Mycoplasma avium subsp Johne’s disease
paratuberculosis Clinical sign >2-5 year old
Granulomatous ileitis +/- ulcers
Malabsorption
Hypoproteinemia
Jejunal hemorrhage syndrome – Sudden death
clostridium perfringens type A? Mechanical obstruction from clotted blood
Necrohemorrhagic enteritis
Any age Clostridium haemolyticum or novyi Liver necrosis and hemolysis
Beta toxin production ® focal hepatic necrosis and
intravascular hemolysis ® fatal
Ddx: copper toxicity in sheep
Taenia ovis/ cysticercus ovis Deadly in sheep
(Intermediate stage) Yellow green cyst in muscle
Emerging disease in Ontario
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Taenia hydatigena (cysticercus
tenuicollis)
Fasciola hepatica Chronic irritation and stricture/ cholangitis
Fasciola magna Adult reside in liver
Can kill a sheep
Parapox virus Proliferating and necrotizing popular stomatitis
(superficial stomatitis)
Actinbacillus lingers Pyogranulomatous togue
Actinomyces bovis Necrotizing and proliferative osteomyelitis
Salmonella High fever
1. Bloody diarrhea or undifferentiated
2. Acute fibrinous necrotizing enterocolitis
3. Dublin – sepsis
FMD Vesicular ulcerative stomatitis of face, teat, feet
Malignant catarrhal fever Lymphoproliferation
Vasculitis
Multisystemic disease
Ulcers in urinary and respiratory tract (mucosal lesions)
Necrotizing arteritis
Ostertagia ostertagi / telodorsagia Diffuse proliferative abomasitis (moroccan leather)
circumcinta Diarrhea and wasting
Haemonchus contortus (sheep) Diffuse pallor
Anemia
Hypoproteinemia
Bottle jaw

Swine
Age group Agent Manifestation
Fetus/Neonates ETEC Colibacillosis
Secretory diarrhea
Intact villi
F4
LT and ST virulence factors to ­ Na and Cl secretion
C difficile Fibrinonecrotic typhlocolitis
A and B toxin Ascites
C perfringens type A Mild nonspecific neonatal mucoid diarrhea
C perfringens type C Sudden death, bloody segmental necrohemorrhagic
Beta toxin enteritis
Rotavirus Villus atrophy
Malabsorptive diarrhea
Coronavirus TGE
PED
Villus atrophy
Malabsorptive diarrhea
Coccidia (cystoisospora suis) Villus atrophy and erosion
Undifferentiated diarrhea
Malasborptive diarrhea
Weaned pigs STEC (edema disease) F18
Shigatoxin
Enterotoxaemia and agiotoxic
Vasculitis, edema
EPEC (Post weaning collibacillosis) Secretory diarrhea
Finisher Brachyspira hyodysenteriae Fibrinohemorrhagic erosive typhlocolitis with mucus
Whipworms Ill thrift diarrhea
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Trichuris suis Milk spots
PCV-2 Multisystemic
Watery diarrhea
Granulomatous disease
Lympholysis and depletion but filled with macrophages
Any age Ascaris suum Milk spots in liver, granulomas, fibrosis
Salmonella enterica – cholerasuis Septicemia, vasculitis
Button ulcers
Mf necrosis, pneumonia
Usually fatal
Salmonella enterica – typhurium Stricture near rectum
Megacolon upstream
Lawsonia intracellularis (weaned & Porcine intestinal adenomatosis – proliferative
grower-finisher) Necrotic enteritis – necrotizing
Proliferative hemorrhagic enteropathy
Clostridium Summary
Clostridium haemolyticum or novyi® ruminant clostridial disease
Clostridum piliformes ® tyzzer’s disease
Clostridium perfringens Type A ® jejunal hemorrhagic syndrome (ruminants) acute hemorrhagic diarrhea syndrome (SA)
Clostridium perfringens Type C ® Beta toxin, necrohemorrhagic enteritis
Clostridium perfringens Type D ® e-toxin angiotoxin, overeating disease, pulpy kidney
Clostidium difficile ® A and B toxin ® typhocolitis
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Clinical Biochemistry
Liver origin enzyme
- ALT
- AST
- GLDH (large animals ALT)
- SDH (USA labile)
Muscle origin enzyme
- CK
- AST
- ALT (must be coupled with muscle injury)
Red cell
- AST leakage from erythrocytes into serum (far away transport)
Enzyme Abbreviation Sources
Alanine aminotransferase ALT Hepatocytes (small animal)
Leakage Skeletal myocytes (massive trauma to release)
Aspartate aminotransferase AST Hepatocytes
Leakage Skeletal ^ cardiac myocytes
RBC
Glutamate dehydrogenase GLDH Hepatocytes (all animals)
Leakage
Sorbitol (iditol) dehydrogenase SDH (DH) Hepatocytes (short half-life)
Leakage Large animals
Creatine kinase CK (CPK) Skeletal and cardiac myocytes
Leakage
Amylase Not often abbrv (AMS) Pancreatic acinar cells
Leakage
Lipase Not often abbrv (LPS) Pancreatic acinar cells
Leakage Hepatic tumour
Induced enzymes
- Stimulus ® ­ production
• Days rather than hours to increase
• Increase can be caused by cellar injury
- Enzyme enters blood, increased activity measured
Enzyme Abbreviation Sources
Alkaline phosphatase ALP Hepatocytes
Induced Bile duct epithelium
Osteoblast (bone isoenzyme)
Steroid induction in dogs or hyperadrenocorticism
(Steroid ALP)
Gamma-glutamyltransferase GGT Bile duct epithelium
Induced Hepatocytes
Hepatocellular injury – leakage enzyme (U/L)
- Alanine aminotransferase – ALT
• SA
- Glutamate dehydrogenase – GLDH
• LA and birds
- Aspartate aminotransferase – AST
• Crummy enzyme in a lot of cells
- Sorbitol (iditol) dehydrogenase – SDH
• Lactate dehydrogenase – LDH
• Arginase – ARG
• Ornithine carbamoyltransferase – OCT
• In USA instead of GLDH
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Enzyme Species Notes
ALT Cat & dog Liver specific for hepatocyte injury or necrosis (unless there is severe muscle injury from
history, then ALT can be from muscle)
- ALT ­ within 12 hours of liver injury (not always immediate)
- If damage resolves, ALT comes down in 2-3 weeks
- May ­ with anticonvulsants administration (eg. phenobarbital - causes damage)
- Not useful in LA or birds
Investigate further when:
- If ALT 2x normal or persistently increased (~1 month)
- Even with marked increases in ALT, liver can regenerate within 3 d ® nothing to see
on biopsy/ pointless (acute liver injury biopsy is useless)
- Only biopsy if increased ~1 month (predicts on going trauma and damage so you can
see something on trucut biopsy)
- Perform coagulation testing first due to possible ¯ liver function
At risk animals
- Middle-aged to older dogs (chronic hepatitis is common)
- Cats (lymphoplasmacytic hepatitis)
® Prompt diagnosis & therapy may increase survival time
- Young dog – consider portosystemic shunt
- Dogs with very poor oral health (+/- ↑ ALP) due to bacteria
- If marked then think toxin
AST Cat, dog, Not liver specific:
horse, * Liver origin (compare to ALT)
bovine * Muscle origin (compare to CK)
* RBCs (serum pink?)
* Pancreas (compare to lipase / amylase, etc.)
Generally, parallels ALT but not typically as high
If damage stops, decreases over 2-3 weeks
GLDH Horse, - Sensitive and specific for hepatocellular injury
bovine, - Uncommonly measured in USA – reagent availability
birds - Don’t use in SA because we have ALT
(cat, dog)
SDH Horse, - There is stability & half-life are issues if not refrigerated / frozen
bovine - Used in USA for detection of liver damage
(cat, dog)
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Induced Enzymes
- ALP – biliary epithelial cells & hepatocyte canalicular surfaces
- GGT – biliary epithelial cells
- Markers of cholestasis, drug effects, endocrinopathies, bone lysis
- Both SA and LA
- Possible ® Cushing and prednisone
Enzyme Species Notes
ALP Cat, dog, Cholestasis
horse, - Liver ALP is predominant isoenzyme
bovine - Induction from cholestasis can be marked
- Can see 4-5x increase in dogs
- Generally takes several days to see increase on biochem
- Cat – less dramatic increases than dogs; but important as T1/2 is short (6 hours). Any ­
is a concern (can imply on going damage)
- LA – Ref interval wide, therefore less sensitive (GGT is a better)
- Horses ® may increase with colic
- Cattle ® works but cholestasis is less common
Other diseases
- Endogenous / exogenous corticosteroids ® induction of ALP in dogs
• equires 7 d exposure
• “sALP” steroid ALP
• Hyperadrenocorticism – good sensitivity, poor specificity ® sALP­ but other
things can cause increase in sALP too
• Can remain increased weeks to months
• If sALP is NOT increased in the dog ® it means hyperadrenocorticism is less
likely (RULE OUT)
- Anticonvulsant therapy (phenobarbital) & phenylbutazone ® can ­ALP
- Hepatic lipidosis/ hyperthyroidism in cat
- ALP is not just liver specific ® present in liver, bone, intestine, kidney, placenta, WBC
But T ½ is shorter for isoenzyme from other sources
Bone-ALP Cat, Dog, - Normal in young animals (growing) 2-3x adult value (higher in foals)
Horse, - Adult animals – 2-4x increase with:
Bovine • Neoplasia involving bone
• Osteomyelitis
Hyperparathyroidsm
• Hyperthyroidism cats
GGT Cat, dog, Cholestasis
horse, - Increase in total bilirubin
bovine - Then look at conj or unconj to see if its pre or post hepatic
- Most GGT is from biliary tree
- More specific for cholestasis than ALP, esp. LA and cats (i.e., fewer things cause it to
increase, it’s not present in bone, etc.)
- Takes longer to increase than ALP
- One source for GGT = liver
- Steroid induction happens in dogs – mild
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Electrolytes
Electrolyte Due to Examples
Sodium & Chloride
Requires knowledge of hydration status
Hyponatremia & Excess loss of NaCl rich fluids or decrease GIT, Renal, sweating, 3rd space loss
hypochloremia intake
Hypochloremia Excess loss of HCl rich fluids only Vomiting
Sequestration ® LDA, GDV
Hyponatremia & Increased total body water Edematous state ® CHF, cirrhosis, nephrotic
hypochloremia syndrome, iatrogenic
Hyperglycemia Mannitol
Dilution of sodium and chloride
Expanding vasculature
Hypernatremia & Dehydration or inadequate water intake Pure water loss ® panting, high fever, heat stress,
hyperchloremia diabetes
Excess Na intake Ingestion ® salt poisoning
IV administration
­ Aldosterone
Hyperchloremia Renal tubule acidosis Less common
Selective HCO3 loss
Potassium
Serum K is not a reliable indicator of total body K (intracellular and extracellular)
Low serum K always indicate TBK depletion
Hyperkalemia Shift from ICF to ECF Acidemia
Muscle damage
In vitro hemolysis – pseudohyperkalemia
Increased TBK ¯ excretion (renal failure, ruptured bladder,
hypoadrenocorticism)
Iatrogenic
Hypokalemia Decreased intake Anorexia, poor diet
Shift from ECF to ICF Alkalemia
Increased loss ETEC diarrhea, sweating, reneal, burns
Hyperosmolality
A. Increased solutes:
• Hypernatremia, hyperglycemia, azotemia/uremia
® Normal osmol gap (Osm measured – Osm calc = )
• Ethylene glycol toxicity, mannitol or radiographic contrast medium, methanol, paraldehyde
® Increased osmole gap
B. Decreased ECF volume
• water loss > electrolyte loss
® Dog hot day
Hyperosmolality may or may not cause clinical problems
- Without fluid shift
• ICF osmo = ECF osmo
• Uremia
• No clinical signs attributable to increased osmolality
- With fluid shift
• ICF osmo < ECF osmo
• Salt toxicity, diabetes mellitus, EG toxicity
• Neurological signs attributable to increased ECF osmolality
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Dehydration – Laboratory evidence
- Dehydrated animal – albumin USG, PCV
- Look at the sodium and chloride
• Both elevated ® hypertonic dehydration
® Dehydration due to pure water loss as with evaporation from the respiratory tract from panting
® Water loss > NaCl loss
• Sodium and chloride within reference interval ® isotonic dehydration
® Renal disease or diarrhea
® Water loss = NaCl loss
® High albumin, Na Cl within reference
• Both below reference interval ® hypotonic dehydration
® Secretory diarrhea, vomiting, heat stress
® Sweating horse
® NaCl loss > water loss
Acid-Base
Metabolic acidosis: Loss of HCO3
A. Increase in acid – titrating out HCO3
• Ketones (diabetes, ­ b-hydroxybutyrate, ­ in lactate, shock, unperfused tissue anaerobic metabolism)
• lactate
• uremic acid (kidney failure)
• toxin (ethylene glycol, salicylate, NH4Cl)
B. Decreased base – loss of HCO3
• Diarrhea, ileus, ptyalism (ruminants can’t swallow saliva), urinary loss
- Compensation = respiratory alkalosis
• ¯ pCO2
• ¯ HCO3
Respiratory acidosis: Gain of pCO2
A. Hypoventilation
• Anesthesia, abnormal muscle function, diffuse pulmonary disease
• altered CNS function (anesthesia)
• ­ pCO2 (hypercapnia)
• Large animal under GA
- Compensation = metabolic alkalosis
• Kidney try to bring more bicarb back into body
Metabolic alkalosis: Loss of HCO3 Gain
A. Sequestration/ loss of HCl
• Abomasum/ rumen (DA)
• Blocked pylorus (foreign body)
• Vomiting/ reflux (vomiting stomach content)
• Ileus (bicarb hanging on in stomach)
B. Increased base
• Administration of HCO3 (iatrogenic)
- Compensation ® respiratory acidosis
• ­pCO2
• Mild increase in pCO2 on blood gas
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Respiratory alkalosis: Loss of pCO2
A. Hyperventilation
• Hypoxemia
B. Hyperthermia stimulation of medullary respiratory centre
• See ¯ pCO2 on blood gas
- Compensation ® metabolic acidosis
Mixed acid-base disorders
- Respiratory and metabolic both with underlying abnormality
- Therefore, both affect pH
• e.g., Simultaneous metabolic acidosis & respiratory acidosis
• e.g., High AG with low chloride
- The compensatory response to a primary abnormality is NOT considered a mixed disturbance
- Low pCO2 = hyperventilation
Anion gap
- Biochemical profile: Na+ K+ Cl- HCO3-
• Cations: Ca2+ Mg 2+
• Anions: proteins, phosphate, sulfate, lactate, metabolite of
ethylene glycol, salicylate
- AG=(Na+ +K+)–(Cl- +HCO3-)
• Hypoproteinemia ® decreased AG
• Hyperproteinemia ® increased AG

Strong ion gap

- Clinical Pathology reference intervals
• 15-26 mmol/L SA
• 13-22 mmol/L LA
- When SID is high we have alkalemia
- When SID is low we have acidemia
- Alkalemia
• Loss of Cl-
® DA, Vomiting etc
• Increased Na+ or K+
® Dehydration
® ­ potassium (hypoadrenocorticism/ no aldosterone)
- Acidemia
• Increased Cl
® Not common
• Loss og Na, K, HCO
® Secretory diarrhea, losing Na and HCO3
® Renal tubular acidosis
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Minerals
Hypocalcemia
- Hypoalbuminemia – ionized Ca normal
- Pancreatitis ® lead to inflammation of fatty tissue and calcium is precipitate out of it and lead to calcemic
• Saponification of fat
• Calcium precipitates out of damaged fatty tissue
- Kidney failure
• Hypovitaminosis D – Dogs, cats, cattle
- Hypoparathyroidism
- Decreased intake or absorption (ruminants)
- Milk fever – calcium into milk
Clinical signs of hypocalcemia
- Dogs: generalized tetany, seizures
- Cows: hyperesthesia (pain) and tetany early, paresis to flaccid paralysis, later
• Exagerated response to pain signals
• No calcium to contract muscle
- Nervousness, anorexia, stilted gait ® hypomagnesium ddx
- Hyperventilation, numbness

Hypercalcemia
- Kidney disease in horses
- Vitamin D toxicosis
• Vitamin D analogue creams (exogenous)
- Osteolytic bone lesions
• Bone lesion
• Osteomyelitis
- Primary hyperparathyroidism
• ­ hormones secreted
- Hypoadrenocorticism
• Dehydration in Addison patient?
- Multiple myeloma (2 reasons)
• ALP, Calcium ­­
• Immunoglobulin attract calcium
- Neoplasia - PTH-rp production
• T-cell lymphoma
• Anal sac carcinoma
Clinical signs
- Concentrating ability of collecting duct of kidney
- PU/PD
• Interferes with concentrating ability
• Tends to cause renal failure by tubuloglomerular mineralization
• Aquaporin – water goes out to urine
- Lethargy, weakness, constipation
- Mineralization of soft tissue
• When calcium and phosphorus are increased
• Calcium x phosphorus product
® > 5.6 predicts tissue mineralization
® >70 in US units ® mineralization
® Mineralization of glomeruli, tubule, gastric mucosal, kidney
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Hypophosphatemia
Less common finding
- Parturient paresis in cows
- Vitamin D deficiency / malabsorption
- Diabetic ketoacidosis & treatment with insulin ® glucose ® phosphorus goes into cell
- Early hyperparathyroidism and humoral hypercalcemia of malignancy (HHM)
• Phosphorus activity
• Ca cause kidney damage
Hyperphosphatemia
- 6 months ® growth of bone so high phosphorus (normal)
• Phosphorus and ALP to make bone
- 12-yo ® cardiac disease, ¯ GFR, history, bad USG (n= 1.030),
kidney disease
• Not good to be high P
• Dehydration
• Shock
• Iso-urine (same as plasma) not good
- 8-yo ® hemolytic anemia, release of phosphorus
Magnesium
- Serum– red top – mmol/
- Serum Mg ® poor indicator of total body Mg
• 3 fractions similar to Ca
• Ionised Mg, but is not measured
• NB: cows can have near-normal serum Mg and tetany due to low CSF Mg
® Can have down cow or they are super crazy
- ¯ GFR will ­magnesium
- Some hormonal influence but not strictly hormonally regulated like Ca
• Intestinal absorption
• Renal excretion
• Milk excretion
Excretion of Mg
- Feces – unabsorbed
- Kidney
• ¯ GFR ® ­ Mg
• ­ GFR ® ¯ Mg
- Mammary gland during lactation
• Milk has 5x as much Mg as serum
Hypomagnesemia
- Hypoalbuminemia (hypoproteinemia)
- Malabsorption ® GI loss, lack of update
- ­ GFR ® ­ renal loss
- Cattle on Mg deficient or K-rich pasture
• Hypomagnesemic tetany
• Clinical sign
® Hyperexcitability
® Tremors, fasciculations, ataxia, tetany
® Cardiac arrhythmias – heart sounds loud
Hypermagnesemia
- Decreased GFR ® ­ Mg
• Dehydration
• Anuric kidney failure or urinary obstruction
- Iatrogenic
• Mg-containing laxatives or antacids
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Lipids & Proteins
Lipemic samples
- Caused by triglyceride chylomicrons post prandially
- Or VLDL that contain triglyceride (less common reason)
Hypolipidemia
- Hypopcholesterolemia
1. Liver failure / portosystemic shunt
® Often result in hypocholesterolemia
® Not enough to make cholesterol
® PS: Nothing is getting to liver
® NB: animals with concurrent cholestasis (bile and cholesterol not getting out, hyperbilirubinemia
and hypercholesterolemia)
2. Hypoadrenocorticism (Addison disease)
® Bilateral adrenal affected
3. Hypocholesterolemia and hypotriglyceridemia
® Maldigestion/ malabsorption (bad smell) ® no pancreatic lipase or there is problem with
mucosal barrier (lymphoma, lymphangiectasia)
® Protein losing enteropathy ® lymphoma, lymphangiectasia ® loss of lipid from body
® Cachexia starvation
Primary hyperlipemia
- Inherited
- Miniature schnauzers
Secondary hyperlipidemia
- Primary is inherited and uncommon (diagnosis of exclusion)
1. Dog
• Hyperadrenocorticism, hypothyroidism, diabetes mellitus (DM), cholestasis, pancreatitis, obesity
• Protein-losing nephropathy (PLN), glucocorticoids, phenobarbital (treatment of seizure)
• Idiopathic hyperlipidemia of miniature schnauzers with pancreatitis ß mechanism not determined
2. Cat
• Negative energy balance (NEB), cholestasis, hyperthyroidism, DM
• Protein-losing nephropathy (PLN), obesity, glucocorticoids
• Pancreatitis ß mechanism not determined
3. Ruminant, pony, minature horses, donkey, sheep, llamas
• NEB, Negative energy balance ® fatty liver
• Pituitary Pars Intermedia Dysfunction (PPID) & Equine Metabolic Syndrome (EMS) – horses & ponies
(obesity) ® can’t process lipids properly
• Pregnancy toxemia of sheep

Serum protein abnormalities

- Hyperfibrinogenemia
• Inflammation
• Dehydration (TS­, albumin­)
- Hypofibrinogenemia
• Consumptive coagulopathies – disseminated intravascular coagulation (DIC)
• ¯ production
• Liver failure
- Hyperproteinemia
• ­ albumin +/- ­globulin
® Dehydration (hemoconcentration)
* Skin tent/ PCV/ urea/ creatinine/ USG
® (Corticosteroid-associated ® making animal pee more)
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
• ­ globulin and ¯ albumin
® Increased protein synthesis
* Albumin decreases to balance out plasma oncotic
pressure
A. Due to infectious & non-infectious inflammatory disease
(®fibrinogen from liver)
* Chronic inflammation ® a broad base peak and not
higher than albumin
B. B-cell neoplasia (lymphoma / multiple myeloma) ® B cell
differentiate to plasma cell
* Can have clonal proliferation of globulins
* Monoclonal gammopathy ® single type of plasma cell
replicated many times ® spike in one reason (as tall or
taller than albumin spike)
Multiple myeloma – Monoclonal gammopathy
- Require findings
1. Monoclonal gammopathy
2. Increased plasma cell in bone marrow
• >20 percent
• Unusual to see plasma cells in peripheral blood
3. Bence-jones proteinuria (light chains)
4. Lytic lesion in bones (rare in cats)

Common Causes of hypoproteinemia

- Increased loss
- Inadequate production
- Inadequate intake
- Dilution
Hypoproteinemia – patterns of loss
- ¯ Albumin and ¯globulin
• Protein losing Enteropathy
® Lose globulin and albumins
® inadequate plane of nutrition
® Sterrahea, bad smelling
• Hemorrhage ® ancylostomiases, parasitism, haemonchus, ulcer
® Something taking blood out
® Chronic ulceration, parasitism
• Exudative skin disease
® Loss of protective barrier of skin
® Plasma oozing out of capillary
® Loss from system
• Lead to: Pan-hypoproteinemia (all proteins lobe)
® Decrease of protein over all
- ¯ albumin
• PLN (nephropathy)
® Hallmarks are low albumin and high cholesterol
® Hypercoagulable
® Can lose plasma oncotic pressure ® ascites
• KIDNEY***
® Kidney not functioning ® losing albumin, anti-thrombin, lose plasma oncotic pressure ® possible
to get ascites (water in abdominal cavity ® decrease vascular fill)
® Protein in the urine
® Amyloid formation ® nephrotic syndrome ® alpha 2 macroglobulin damage
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
- ¯ albumin and ­ globulins
• Inflammation
• Advanced liver disease and <20% functional tissue
® Not enough of Kupffer cells so antigen end up in the lymph nodes ® B cells start producing
immunoglobulin and turn to plasma cell ® ­­ plasma cells
® And also ¯ albumin due to liver failure
• Disease: Cirrhosis, neoplasia, necrosis, inflammation
• PSS leading to hepatic atrophy
- ¯ globulin
• Failure of passive transfer (FPT)
® Foal or calf biochem
• Give replacement plasma
- ¯ albumin and ¯ globulin (iatrogenic)
• PLE, malabsorption/ maldigestion
• Cachectic states (neoplasia?, not able to eat, TNFa­)
• Intestinal parasitism
• Hemodilution (if too much fluid)
• Repeated effusion (bad)
• ¯ albumin and ¯ globulin due to iatrogenic reasons
® Hemodilution
® Repeated effusion draining
Hemolymphatics
Bone marrow
- Function
• Major hematopoietic organ in adults
• Major site for B-cell development throughout life (except birds)
Hyperplasia (increased demand)
- Loss of RBC/ platelet
• Hemorrhage, hemolytic anemia etc
- Inflammatory stimulus
• Liver abscess, pneumonia
- See Reddening of end osteo bone marrow*

Replacement (myelophthisis)
- Myelofibrosis, chronic leukemia
- Replaced by cell, fibrous tissue
- Serous atrophy of fat is a type of replacement
• Cachexia, starvation
• Fat is metabolized, bone marrow reticular cells produce the mucoid substance
Neoplasia
- Lymphoma, multiple myeloma, osteosarcoma etc
Infection
- Osteomyelitis
- Infection in the bone
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Thymus
- What % of T-cells exit the Thymus? 2%
- 2 main cell types of thymus
• Lymphocyte
® Little blue cells in lobules
• Epithelial cell (Hassall’s corpuscles)
® Big
- Involution ~6 mos - Sexual maturation
- 3 zones
• Subscapular: T- cells from bone marrow enter
thymus
• Cortex: positive/ negative selection + TCR
rearrangement
• Medulla: negative selection
Spontaneous idiopathic thymic hemorrhage
- Proposed pathogenesis
• Thymic involution ®
• Diagnosis of exclusion
- Required: Currently undergoing thymic involution
• Signalment: begins at 6-12 mos depending on the breed
Ingestion of anticoagulant rodenticide
- Absence of evidence of thymic involution
- Extensive hemorrhage
- Pre-onset to sexual maturation
- No history of trauma
- Died Suddenly
- Vit K deficiency
- R/O: Trauma, anticoagulant rodenticide
• History: 11-month canine
• Physical examination
• Clotting times
• Examination of ingesta
• Toxicological screening for anticoagulant rodenticides
Thymoma
- Multilobulated mass
- Thymoma
- Uncommon
- Diffuse or localized
- Thymoma (thymic carcinoma) = localized mass
• Different types of thymoma ® epithelial or lymphoid rich or mixed
- Paraneoplastic syndrome with thymoma
• Dog: Myasthenia gravis
• Cat exfoliative dermatitis
Pathogenesis of MG
- Myasthenia gravis secondary to thymoma
- Muscles affected
• Esophagus
• Eyelids
- Thymoma ® develop autoantibodies against thymic myoid cells (which have ach receptors) ® antibodies in
systemic circulation ®bind to achr on posynpatic membrane at the NMJ ® prevent ach binding ® prevent
muscle contraction ® muscle weakness
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Spleen
Histiocytic sarcoma
- Type 1: Macrophage (red pulp)
• Ddx:
® lymphoma and amyloidosis
- Type 2: dendritic cell (white pulp)
• Ddx:
® metastatic neoplasia and abscess
® Could also be lymphoma maybe

Lymphoma
- can look diffused or nodular

Abscess

Infarction
- On the edge of the organ
• Always on the margin
• Never in the centre
- White vs. dark infarct ® difference is in age
- Dark red and bright red ® venous or arterial
Hemangiosarcoma
- How do we differentiate between hematoma and
hemangiosarcoma?
• Histology
- Sampling
• Fix it in clinic for a few days
• Wrap it and moisten with formalin

Congestion
- DDX
• Barbiturates
• Volvulus
• Septicemia

Amyloidosis
- Margins are expanded
- Waxy appearance
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su

Siderotic plaques
- Normal attachment parts of the spleen
- Build-up of blood product and minerals
- Not significant and increase with age
- Rough looking
Traumatic fracture
- Separated and functional
- Splenosis

Lymphatics
Lymphedema
- Lymphatic obstruction most common, arteriovenous shunt
- Edema in lymph
Lymphangitis
- Usually occurs with lymphadenitis, not as primary lesion
- See the little tubes into intestine
- Johne’s disease
Lymphangiectasia
- Developmental
- Acquired: obstruction (neoplasia, inflammation) but usually idiopathic
- Protein losing enteropathy clinically with dilated lacteals histologically

Lymphangiosarcoma
- Neoplasia of lymphatics
- Cats: Ventral abdomen, poor prognosis
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Lymph node
Sizes/ hyperplasia
- Does it go back to normal or not?
- If it stays big ® neoplasia?
- Reversible?
• Hyperplasia is
• Neoplasia is not
Strangles
- Streptococcus equi ssp. equi
- Mandibular and retropharyngeal lymph nodes
- Spread to abdominal lymph nodes = gastric strangles
Caseous lymphadenitis (CLA)
- Diffused or nodular
- Pathogenesis
• Skin wound (shearing) → Corynebacterium pseudotuberculosis penetrates skin → drains to regional lymph
node → systemic circulation → localizes to internal lymph nodes, lungs, spleen
Granulomatous lymphadenitis
- PCV-2 in pigs
- Mycobacterium bovis avium (johnes)
- Bronchial lymph nodes
Neoplasia
- Lymphoma
• Neoplastic lymphocytes forming solid tumours
• Secondary leukemia possible
- Leukemia
• Neoplastic lymphocytes in bone marrow and blood
• Secondary formation of solid tumour possible
• More likely in blood (not setting up shop)
® Bovine lymphoma
- Enzootic (BLV associated)
• Multicentric
• Widely distributed in LNs
• Uterus, abomasum, myocardium, spinal
- Sporadic (not BLV)
• Multicentric
® Calves <6 mos
® LNs and organs and bone marrow
• Thymic
® 6-24 mos
® Massive enlargement
• Cutaneous

Mucosa-associated lymphoid tissue (MALT)

- Lymphocytes and dendritic cells in mucosa of organs ® BALT, GALT, CALT etc, peyer’s patches, bursa of fabricius,
pharyngeal and palatine tonsils
- Act as sentinel protecting mucosal barrier
- B- cell development in Peyer’s patches (ruminants) and Bursa of farbicus (birds)
- Pathology
• Atrophy ® viral, toxin, radiation
• Hyperplasia ® antigenic stimulation
• Inflammation ® eg. tonsilitis
• Neoplasia ® eg. lymphoma, SCC
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Hemolymphatic System (Bienzle)
Conditions affecting the hemolymphatic system
1. Hypoplasia or atrophy ® immunodeficiency Components of the
2. Hyperplasia ® immune reactivity hemolymphatic system
- Thymus
3. Inflammation ® aka lymphadenitis
- Spleen
4. Infection
- Bone marrow
5. Neoplasia - Lymph nodes
- Cells in blood ® granulocyte,
Hypoplasia: SCID in dogs lymphocyte, RBC, platelet,
- Lymphocytes do not go beyond being a T lymphocyte ® they don’t make monocyte
cytotoxic lymphocyte or plasma cells
- Presentation
• Opportunistic organisms can cause illness
- Diagnosis
• Look at total antibody
• CBC ® lymphopenia
• Globulins ® immunoglobulins

Normal process of cell-mediated immunity

1. Naïve helper T lymphocyte meet antigen
2. Produce cytokine to help B lymphocytes become plasma cells
and cytotoxic lymphocytes to become killer cells
[Produce interleukins (2, 4, 9, 15) to make cytotoxic leukocytes
and plasma cells]

Hypoplasia: SCID in horses

- Enzyme (recombinase) that makes new lymphocyte receptors is dysfunctional ® they don’t recombine genes ®
non-diverse lymphocytes
- Arabian horses – 1 defective copy
- Presentation Normal process of making a
lymphocyte receptor
• Opportunistic infection, bloody diarrhea
- Ability to make new receptors
- Diagnosis
- Cut chromosome and put them
• Low globulins back together (recombinase)
• NK cells are intact
• May recognize lipid molecules on antigens

Hyperplasia: Reactive lymphoid - Inflamed lymph nodes are

- Immune system working TENDER to touch
- Follicular hyperplasia ® B cells - Lymphoma lymph nodes are NOT
- Paracortical hyperplasia ® T cells tender
- Sinus histiocytosis ® macrophages
- Cell function
• T cell – produce cytokine that influence B cell to become plasma cells
• Plasma cells – attach to bacteria
• Cytotoxic T cells – cell lysis
- After antigen has been delt with, lymph node will return to normal size (apoptosis)
- Only memory lymphocytes survive and stay in the lymph node
- Diagnosis of immune activation
• Hyperglobulinemia
• Inflammatory cells
• Serum amylas A
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Bone Marrow (Bienzle)

Cell type Circulation length

Neutrophils Less than a day, highly active
Eosinophils Live in tissue for a while, don’t stay in blooe for long (IL-5, Basophil)
Platelet 10 days
Erythrocyte 120d in dogs
60-70d in cats
® if something happens to precursor cells you will see neutropenia first
® 2-3 days to produce erythroid or granulocytes in bone marrow
® 6 days to produce new neutrophil from undifferentiated precursor cell
® Proportion of granulocyte precursor to erythroid precursor (M:E) = 1:1 in dogs and cats, 1:2 in large animals
Bone marrow biopsy
- Core biopsy
• Formalin fixed, paraffine embedded
- Bone marrow aspirate
• Thick blood, make direct smear

Blood samples
Cell Function/ characteristics
Neutrophils - Storage pool in bone marrow
- Wall of blood vessel
- In blood
- Stress causes ­
Lymphocytes - Long lived cells
- Mostly in tissue and lymphatics
- Stress cause ¯ (stay in lymph nodes instead of circulating)
Rubricyte - Mature RBC that can carry oxygen
- Maturation ® decrease in size and nucleus becomes dense ® apoptosis ®
nucleus expelled ® become RBC and circulate for longer
Granulocyte - Immature granulocytes (metamyelocyte) have indent nucleus that is band
- Mature ® segmented nucleus
Megakaryocyte and - Only normal giant cell
osteoclast - Megakaryocyte ® give rise to platelets, multilobulate nuclei
- Osteoclast ® individual nuclei
- Can be in bone marrow

Bone marrow in relation to peripheral blood (CBC)

Regenerative anemia - Polychromatophils in blood
- Many erythrocytic percursors (rubricytes)
Suppurative - Neutrophils
inflammation with left - Septic= see bacteria
shift - Looks blue
Hemolytic anemia - Agglutination of RBC
- Spherocytes
- Ghost cells (lysed RBC)
- Free hemoglobin in blood
- Large numbers of rubricytes in bone marrow (dark cells)
Heinz body - Oxidative damage
- Oxidation of hemoglobin
Immune-mediated - Petechia hemorrhage on mucous membrane
thrombocytopenia - See a lot of megakaryocytes
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Non-regenerative - Iron deficient anemia
anemia - Due to: chronic blood loss from GI tract- tumour, lymphoma, carcinoma
- Blue staining = hemosiderin that has iron
- Hypochromic RBC
- Low MCHC, low Hct/ Hgb/ RBC
Lead toxicity - Abnormal rubricytosis
- No maturation of RBC
Multiple myeloma - Neoplastic clonal cell
- Diverse immunoglobulin is not occurring
- Monoclonal peak – only 1 globulin

Acute lymphocytic - Non-regenerative anemia

leukemia - Mitoti figures
- Almost no rubricytes
- Predominantl round blue cells
- Bone marrow involvement ® Undifferentiated cells
- Marked cytopenia
- Sick animal
- Rapidly progressing (fatal)

Chronic leukemia - Rare

- Large number of normal cell in blood
- Chronic neutrophilic leukemia, lymphocytic leukemia
Myelodysplastic - Production of abnormal cells
syndrome - Chronic cytopenia, not very ill
Bone marrow - Aplastic anemia
hypoplasia - Pancytopenia
- Infections causes ® anaplasma, parvovirus, FeLV
- Drugs ® estrogen, phenylbarbital, chemo
- Toxin ® bracken fern
- Idiopathic ® autoimmune
Myelofibrosis - Overgrowth of bone marrow cavity by fibroblasts
- Caused by aberrant cytokine production by chronic bone marrow stimulation
® LEUKEMIA, idiopathic
- Cannot aspirate
- Diagnose depend on biopsy
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Lymphoma
- Most common cancer in animals, most are malignant
- All ages
- Nodal vs. extranodal lymphoma
Cause of lymphoma
- Clonal proliferation at any stage of lymphocyte ® naïve T lymphocyte, activated T lyphocyte, resting B
lymphocyte, precursor lymphocyte, plasma cell, NK cells, lymphocytes in MALT
- Lymphocytes normally rearrange DNA for receptors ® more prone?
- Pro-oncogenes
Lymphoma in dogs
- Middle-aged
- Multiple large LN – non painful
- Hypercalcemia is commonly associated with T-cell lymphoma
• Tumour production of PTH-like molecules that cause bone resorption, intestinal Ca absorption, renal Ca
preservation
Diffuse lymphoma Most common
Nodular (follicular) Uncommon
lymphoma Big follicles that are relatively uniform

- Diagnosis 20-40 % nodal lymphomas and all

• Aspirate one or several enlarged lymph nodes and make 5-10 thin mediastinal lymphomas are T cell origin
smears – Majority of lymphomas are B cell
• Submit unstained slides to lab lymphomas
• Usually can diagnose from cytology (dog)
- Features
• Primary ocular, nervous, GI, renal
• Do not have lymphocytosis but lymphopenia ® blood is not a good way to diagnose
• Secondary leukemia possible
Lymphoma in cats
- More frequently extranodal ® eg. CNS, intestinal lymphoma, kidney Mediastinal lymphoma almost always T
(bilateral), liver cell type
- T cells more common
- in FeLV and FIV infected cats and associated with hypercalcemia
Feline leukemia virus - Retrovirus
- Picks up cellular proto-oncogenes
- Uncommon
- Only mediastinal lymphoma is common with FeLV infected
cats
Feline immunodeficiency - Retrovirus
virus - Slow progressive disease
- Loss of CD4+ helper cells
- Opportunistic infections
- Aggressive extranodal lymphomas common with FIV cats
- Indirect effect (no virus in tumour cells)

Lymphoma in horses
- T cell lymphoma > B cell lymphoma
- Associated with inflammation and anemia
- Cutaneous lymphoma
• Older horses
• Wax and wane in response to steroids
- Mesenteric lymphoma
• Associated with immune hemolytic anemia
• T cell origin
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
- Gammopathy is more common in horses
Lymphoma in ruminants
- Due to BLV infection
- Persistent lymphocytosis
- Lymph nodes + abdominal organs
- Rare in young cattle
Lymphoma classification
- Histopathology : Architecture and morphology of lymph node
• Diffuse
• Nodular
- Immunophenotype
• CD expression of tumour cells
- Good prognostic information in dogs
- Cytogenetic, molecular testing
Cause of hypercalcemia
1. Primary hyperparathyroidism (increased PTH)
2. Hypercalcemia of malignancy (PTH-like factor) - lymphoma, anal sac
Hypercalcemia interferes with renal tubular
apocrine adenocarcinoma, other carcinomas
function ® lead to renal mineralization ®
3. Renal failure - aberrant PTH secretion? azotemia
4. Hypervitaminosis D (rodenticides, granulomatous disease)
5. Hypoadrenocorticism (Addison's disease) Renal dysfunction ® reduce EPO production
6. Osteolysis (tumors, infection)

Derm Path (Foster & Bienzle)

Skin Biopsies
• Minimum of 3 samples (6 is good)
• Indications for
o Nodular skin lesion, suspected epitheliotropic lymphoma, fail to respond to therapy, suspected
autoimmune disease, persistent alopecia
o Clinical work up is unsuccessful
• Reasons to NOT do a skin biopsy
o Pattern is not specific enough to indicate the cause of disease
o Requires clinical separation of causes
Epithelium
- Stratum basale ® basement layer
- Stratum spinosum ® spinosal keratinocyte with desmosomes
- Stratum granulosum ® granular keratinocyte Definition:
- Stratum corneum ® squamous keratinocyte, lipid substance – Tricho and pilo = Hair
important for innate immunity Kerato = keratin producing
Hair follicle Acantho = spiny
- Infundibulum ® outer, epidermis part of hair follicle Fibro = dermal and SC connective tissue
- Isthmus ® middle of hair follicle, sebaceous duct and arrector pili Myxo = watery. Loose in SQ
- Inferior portion ® bulb and dermal papilla of hair follicle Leiomyo = arrector pilli muscle
- Alopecia = loss of hair, disease of hair production or secondary Rhabdomyo = skeletal muscle
alopecia Lipo = adipose tissue
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su

Neoplasia
- Infundibular keratizing acanthoma ® Superficial/infundibulum follicular neoplasm
- Tricholemmoma ® Middle / isthmus and inferior follicular neoplasm
- Pilomatrixoma ® Inferior/ deep follicle neoplasm
- Trichoepithelioma ® Combination of follicular components that are neoplastic
- Soft tissue sarcoma ® mesenchymal neoplasm
- Feline injection site sarcoma ® highly infiltrative and metastatic

Inflammatory pattern analysis

Inflammatory Non-inflammatory
• Crusting dermatitis (inflammation) • Cornification (scaling dermatosis)
• Perivascular dermatitis • Follicular disorders
• Vesiculopustular dermatitis • Collagen disorders
• Folliculitis, furunculosis sebaceous adenitis • Pigment disorders
• Nodular dermatitis • Physiochemical injury
• Vasculitis • Pigment disorder
• Panniculitis • Physiochemical injury
• Cytotoxic/ interface

Pruritis Perivascular dermatitis

Definition:
Actinic effect ® loss of hair due to exposure to sun
Erythema, red skin ® vascular dilation and endothelial hypertrophy ®
Pruritis ® perivascular dermatitis
Wheal/ hives ® dermal edema
Perivascular dermatitis ® histo for pruritis

Pathogenesis of pruritus
Sensory nerve or neural • Direct stimulation of nerve ® phantom limb, trauma, nerve sheath tumour
processor disease
Sensory detector system • Direct stimulation of IENF (non-inflammatory) ® dry skin (xerosis) or
pruritus intraepidermal lymphocytes
• Chemical mediators (inflammatory) ® insect bite & histamine release, mast
cell degranulation (IgE mediated)
Mechanisms of pruritis
• Dry skin (xerosis)
• Histamine and vasoactive amines from insect bites
• Mast cell degranulation
• Lymphocytes in epidermis

Scaling skin disease Hyperkeratosis

Diseases
• Sebaceous adenitis ® result in scaling skin disease
o Sebum is required for skin barrier function
o No sebum ® inadequate protection of skin and cause hyperkeratosis (scaling)
• Reactive hyperplasia ® Secondary cornification disorders
• Nasodigital hyperkeratosis® Primary cornification disorder - failure to release corneocytes
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Definition:
Comedones ® follicles plugged with keratin
Scale ® accumulation of loose fragment of keratin (stratum corneum) due to decreased loss or increased
production
Flakes ® Dandruff, white, red, brown, yellow
Plaque ® >1 cm flat elevation
Acanthosis ® increase in stratum spinous layer of epithelium
Parakeratosis ® retention of nuclei in stratum corneum, abnormal cornification
Hyperkeratosis ® increase stratum corneum layer
Hyper granulosis ® Increase stratum granulosum layer
Follicular dilation and keratosis ® same thing as comedones
Vesiculopustular disease ® scaling skin disease

Crusting skin disease

Vesiculopustular
Disease
dermatitis
- Pemphigus foliaceous ® Immune mediated disease, non-infectious crusting skin
disease
- Intraepidermal vesiculopustular dermatitis ® Very common, bacterial, fungal, immune mediated
- Subepidermal vesiculopustular dermatitis ® Rare, congeintal ulceration or acquired
- Hemidesmosome disease ® Lifting epidermis from dermis formation of ulcer, erosions (caused by neutrophils,
ringworm, immune mediated)
Pathogenesis
- Damage to keratinocyte and intercellular bridge (desmosome, hemidesmosome and basement membrane)
- Intraepidermal (common) ® bacterial, fungal, pemphigus disease
- Subepidermal (rare)

Definition:
Crust ® Inflammatory exudate that is dried, attached to surface of skin, colour reflects content
Edema ® Low protein fluid
Vesicle ® Fluid filled pocket, due to inflammation (dermatitis), small
Bulla ® Large >1 cm vesicle
Serocellular crust ® Exudate + cell (similar to crust)
Pustules ® When there’s aggregates of neutrophils or eosinophils, small, elevation of epidermis
Vesicular and pustular dermatitis ® Crusting skin disease, aka vesiculopustular dermatitis
Subprabasalar ® Above basal layer vesicle
Subepiderma ® Under basal layer vesicle
Balloon degeneration ® Cell swelling
Spongiosis ® Edema within the cells of epidermis

Nodular skin disease

Disease
- Folliculitis ® Inflammation of follicle (luminal target center, mural target wall of follicle), mainly caused by
bacteria, dermatophyte, demodex
- Furunculosis ® Inflamed follicle and ruptured
- Nodular skin diseases ® Target hair follicle and adnexa or targets panniculus
- Sebaceous adenitis ® Inflammation of sebaceous gland, type of mural folliculitis, lack of sebum lead to dry skin
and hyperkeratosis (similar to scaling skin disease – vesiculopustular disease)
- Patterns
o Folliculitis: follicular targeting
> Sebaceous adenitis
o Nodular: diffuse dermatitis, in dermis but no follicular targeting
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
> Bacteria, mycobacteria, fungi, protozoa
o Panniculitis: deep nodules with subcutaneous fat

Definition:
Papule ® Small elevation of skin that is palpable as a solid mass, not fluid filled
Nodule ® Solid elevation in skin greater than 1 cm, involve dermis
Diffuse dermatitis ® In dermis but no follicular targeting
Panniculitis ® Deep nodule restricted to the subcutaneous fat
Folliculitis ® follicular targeting

Erosive and depigmenting diseases

Disease
- Leukoderma ® loss of pigment/ vitiligo
- Hypothrichosis ® congenital lack of hair
- Caused by 3 patterns
o Vesiculopustular disease
o Epidermal cytotoxic disease
o Vasculitis

Definition:
Macule ® Non palpable lesion that is result of alteration of skin pigmentation
Excoriation ® Partial loss of epidermis
Ulceration ® Full thickness loss of epidermis
Kenogen ® Resting follicle with no club hair
Anagen ® Active follicle
Catagan ® Regressing follicle
Telogen ® Resting follicle with hair
Exogen ® Release of club hair

Cytopathology of cutaneous tumours

Round cell tumours
Mast cell – Dogs • Benign to highly malignant
• Big round cells
• Easy to diagnose
• Accompanied by eosinophils
• Isocytosis isokaryosis
• Solitary or multiple, cutaneous, subcutaneous, or internal organs
Mast cell – Cats • Skin, spleen
• Few are malignant in cats
• Often accompanied by eosinophils
Histocytoma • Mostly in young dogs
• Non-haired lesion
• Regression without treatment is common
• Normally no granules, not much pigment and relatively uniform nucleus size
Skin lymphoma Epitheliotropic ® travel into surface layer of skin in epithelium
• Mucosa, paws, skin
• Need histopath for diagnosis
• Head, face
• Non-ulcerated
• Older animals
• T-cell localized or widespread
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
• Chemo is best option
Non-epitheliotropic
• Below epidermis
• Discrete “lumps”
• Waxing nad waning tumours in horses
• Most often B cell type
• Chemo is best option
Plasmacytoma • Tumours os mature plasma cells
• Skin, oral mucosa (larynx, trachea), rectum
• Amendable to cytologic diagnosis
• Benign in dogs, malignant in cats (locally invasive)
• Surgical excision can be curative
Transmissible venereal • Face and genitalia
tumour (TVT) • Histiocytic and neural crest cell origin
Melanoma • Cutaneous ® benign
• Muco-cutaneous or interdigital area ® malignant
• Mostly benign in older grey horses
• Iris melanoma (infiltrative and some metastatic) in cats
Mesenchymal subcutaneous tumours
Lipoma • Common, soft, fatty aspirates
• Liposarcoma has a different appearance and is malignant
Soft tissue stromal • Fibroma, soft tissue sarcomas, leiomyoma
(spindle) cell tumours • Slow growing
• Rarely metastasize
• FNA samples are adequate
Epithelial tumours
• Readily aspirated
• Able to distinguish benign and malignant tumour on cytology
• But can’t distinguish between subtypes
Papilloma • Benign tumours of squamous epithelium
• Viral induced
Squamous cell • Malignant tumour o squamous epithelium
carcinoma • Distinct cytologic feature ® keratin in cytoplasm, nuclear to cytoplasmic
asynchrony, anisocytosis and anisocytosis
Basal cell tumour • Trichoblastoma
• Surgical excision is mostly curative
• Often pigmented in cats
Sebaceous tumours • Tumour of the adnexa
• Highly vacuolated cytoplasm
• Mostly benign
Perianal tumour – Dog • Modified sebaceous gland
• Apocrine gland may give rise to adenocarcinoma ® malignant and cause
hypercalcemia
Perianal tumour – Cat • Apocrine tumours at base of ear ® ceruminous gland adenoma and carcinoma in
ear canal
Cysts and benign hair • Benign
follicle tumours • Epidermal, sebaceous cell or follicular cell
• Cannot distinguish with cytology
• Typical finding ® cell debris, cholesterol crystal, keratin, macrophage, neutrophil
Mammary tumours – • Many benign
Dog • Cytological appearance is NOT predictive of tumour behaviour
Mammary tumour – Cat • Many malignant
• Treating with progestin can cause fibroadenomatous hyperplasia
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Endocrine Pathology (Kirkbright)
Disease in dogs
Pituitary gland • Intermedia adenoma (Pars distalis)
o Productive: ACTH
Adrenal cortex • Nodular hyperplasia
o Incidental, non-productive
• Adenoma ® Cushing’s
o Productive: cortisol
• Atrophy ® Addison’s
o All 3 layers hypofunction
Adrenal medulla • Pheochromocytoma
o Productive or non
o Benign or malignant
• Metastases esp carcinoma and melanoma
Thyroid gland • C cell or follicular carcinoma
o Productive or non
• Idiopathic follicular atrophy/ inflammation ® Hypothyroidism
o Hypofunction
Parathyroid gland • Diffuse hyperplasia
o Secondary hyperparathyroidism
o Productive
• Adenoma
o Primary hyperthyroidism
o Productive
Endocrine pancreas • Islet cell tumour ® Insulinoma
o Carcinoma > adenoma
o Productive
Chemoreceptor • Aortic body Chemodectoma
o Non-productive
o Brachycephalic

Disease in cats
Adrenal medulla • Metastases (esp lymphoma)
o Hypofunction of the gland
Thyroid gland • Follicular adenoma/ adenomatous nodular hyperplasia ® Hyperthyroidism
o Productive
Parathyroid gland • Diffuse hyperplasia
o Secondary hyperparathyroidism
o Productive
• Adenoma
o Primary hyperparathyroidism
o Productive
Endocrine pancreas • Degeneration hydropic or amyloid deposition of islets ® Diabetes mellitus
o Hypofunction
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Disease in horses
Pituitary gland • Adenoma/ multinodular hyperplasia (Pars intermedia)
o Productive
o POMC derivatives
o Insignificant ACTH
Adrenal cortex • Incidental ectopic nodules
• Diffuse hemorrhage and congestion
Adrenal medulla • Pheochromocytoma
o Productive or non-productive
o Benign or malignant
• Metastases esp melanoma
Thyroid gland • C cell or follicular adenoma/ nodular hyperplasia
o Non-productive
Parathyroid gland • Diffuse hyperplasia
o Secondary hyperparathyroidism
o Productive
o AKA “Big head” / “Bran disease”

Disease in ruminants
Adrenal medulla • Pheochromocytoma
o Productive or non-productive
o Benign or malignant
• Metastases esp lymphoma
Thyroid gland • Fetus neonates: Diffuse follicular hyperplasia (goiter) ® hypothyroidism
o Hypofunction
• Bulls: C cell carcinoma
o Non-productive

Disease in ferrets
Adrenal cortex • Hyperplasia & carcinoma > adenoma
o Zona reticularis ® hyperestrogenemia
o Productive
Endocrine pancreas • Islet cell tumour ® insulinoma
o Carcinoma > Adenoma
o Productive

Pituitary Gland
• Most common disease ® proliferation
o PDH Cushing’s
o PPID
o Nodular cortical hyperplasia
> Incidental & common in old dogs
• Dogs and horses

Adrenal Gland
• Diseases
o Cortical neoplasm of adrenal gland (early gonadectomy)
> Older dogs and neutered ferrets
> Due to loss of negative feedback on pituitary gonadotrophs
o ADH Cushing’s ® ZF and ZR
o Addison’s ® All 3 layers
o Iatrogenic administration of glucocorticoids ® All 3 layers
o Pheochromocytoma ® medullary proliferation
> Cattle, dogs, horse
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
• Normal C:M ratio ® 1:2, 1:1, 2:1
o Cortex ® yellow grossly
o Medulla ® red grossly
Thyroid
• Disease
o Follicular adenoma
> Cat (hyperthyroidism common) and horse
o Follicular carcinoma
> Dog
o C-cell adenoma
> Horse
o C-cell carcinoma
> Dog, bull
o Goiter
o Hypothyroidism (dogs)
Parathyroid
• Disease
o Secondary ® diffuse hyperplasia due to renal failure, dietary imbalance, feline hyperthyroidism
o Primary ® parathyroid adenoma
> Functional tumour
o Pseudohypoparathyroidism (humoural hypercalcemia of malignancy) ® Anal sac gland adenocarcinoma
and T-cell lymphoma
> ­ PTH-rp and PTH ¯
Endocrine pancreas
• Disease
o Diabetes mellitus ® amyloid deposition or hydropic degeneration in cats
> Type 1: immune mediated destruction
> Hepatomegaly (fatty liver)
o Pancreas insulinoma
> Isleb B cell neoplasm
> Dogs and ferrets
Chemoreceptor organ
• Disease
o Chemodectoma
> Aortic body (more common)
> Carotid body
Endocrinology (Bienzle)
Canine hyperadrenocorticism (Cushing’s)
a) Pituitary tumour producing ACTH (majority)
o Adenoma symmetry
o ­ Cortisol and ­ ACTH
b) Adrenal tumour
o Adenoma or carcinoma
o Asymmetry
o ­ Cortisol and normal ACTH
c) Iatrogenic (corticosteroid)
o Smaller adrenal glands due to exogenous sypply (bilateral)
Diagnostic approach
1. Clinical suspicion
a. History – depression, PUPD
b. Hematology – stress leukogram (SMILED, neutrophilia/leukopenia)
c. Biochemistry – sALP elevation, cholesterol
d. Urinalysis – isosthenuria (1.008-1.012), mild proteinuria
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
2. Screening test (Sn>Sp)
a. sALP
b. Urinary cortisol/ creatinine ratio (morning sample)
> High NPV and sensitivity
3. Confirmatory test
a. Low dose dexamethasone suppression
> @ 8hrs 90% od hyperadrenocorticism have >40 nmol/L of cortisol
> @ 4hr some suppression = could be Pituitary
> @ 4 hr NO suppression = could be Adrenal
b. ACTH stimulation test
> Inject ACTH IV and measure cortisol at 1 hr (dog) ½ hr (cat)
> Hyperadrenocorticism (hyperplastic adrenals) = exaggerated response of ­ plasma cortisol
® PDH – 85% will have exaggerated response
® ADH – 60% will have hyper-response
4. Distinguish between PDH or ADH
a. Low dose dexamethasone suppression
b. High dose dexamethasone suppression
> Adrenal tumour secrete cortisol entirely independent of negative feedback
> Most dogs with pituitary tumour will suppress
c. Endogenous ACTH concentration
> Measure ACTH
> PDH ® ACTH overproduction
> ADH ® ACTH underproduction
Feline hyperadrenocorticism
• Uncommon
• Almost always pituitary origin
• Insulin resistance/ diabetes mellitus related
• Diagnosis
o Hyperglycemia, gucosuria, increase ALT
o Big faces
o Dexamethasone suppression test
o Plasma ACTH
o Urinary cortisol/ creatinine ratio
Equine hyperadrenocorticism
• Pituitary pars intermedia dysfunction
• Hypertrichosis, hyperglycemia, PUPD, glucosuria
• Common in older horses
• Lack dopamine production, neurogenerative
• Overproduction of POMC ®ACTH precursor
• Diagnosis
o Endogenous ACTH
• Treat with pergolide (dopamine agonist)
Ferret hyperadrenocorticism
• Bald ferret
• Adrenal hyperplasia or adrenal carcinoma (sometimes adenoma)
• Diagnosis
o Imaging, measure sex hormones

Canine Hypoadrenocorticism (Addison’s)

• Disease of young to middle aged females
• ¯ cortisol and aldosterone
• Often present in crises
• Atrophy and hypofunction of adrenal cortical cells
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Diagnostic approach
1. Clinical suspicion
a. Bradycardia, hypovolemic
b. Hematology – lack stress leukogram
c. Biochemistry – electrolyte abnormalities, prerenal azotemia, hypercalcemia, hypoglycemia
d. Urinalysis – inadequate concentration
2. Screening test
a. Na/K ratio – Hyponatremia and hyperkalemia (<23:1)
3. Confirmatory test
a. ACTH stimulation test
> Adrenals are atrophied ® nothing will happen (<30 nmol/L at baseline and <50 nmol/L at 1 hour)

Canine Hypothyroidism
• Most commonly primary
• Immune reaction - T3 is more biologically active than T4
Diagnostic approach - rT3 is inactive
1. Clinical suspicion - T4 enter cell and is de0ionated to free T3
a. Breed – English setter, Doberman, golden retriever - Most bound to thyroid-binding globulin
b. Age – mid age
c. Clinical sign – weight gain, lethargy, dermatopathy
d. Biochemistry – fasting hypercholesterolemia and hypotriglyceridemia (milky serum)
2. Confirm hypothyroidism
a. Total T4 concentration - <8 nmol/L is very likely
> Drugs that decrease T4
® Glucocorticoid
® NSAID
® Phenobarbital
® Androgen
® Sulfonamides
> Drugs that increase T4
® Narcotic analgesic
® Halothane
® Prostaglandin
® Insulin
b. Free T4
> Bypass euthyroid sickness (distinguish between euthyroid from hypothyroid)
> <9 pmol/L
c. Endogenous TSH concentration
> ­­ TSH (>0.70 ng/ml)

Feline Hyperthyroidism
• Common in aged cats (12yrs)
• Multinodular
Diagnostic approach
1. Clinical suspicion
a. Clinical signs – weight loss, PUPD, hyperactivity, tachycardia
b. Physical exam – palpable cervical mass, small kidney
c. Stress leukogram
d. Elevated hematocrit
e. Azotemia
f. Hyperphosphatemia
g. ­ALT and ALP
h. Steatorrhea
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
2. Confirmatory test
a. Total T4 (>75 nmol/L)*
b. Free T4
c. Imaging
d. T3 suppression test
> Giving T3 (oral) should suppress TSH and decrease T4
> Hyperthyroid cats T4 secretion by adenomatous thyroid gland is unresponsive to ¯ TSH
concentrations

Equine Hyperthyroidism
• Older horses
• Emaciation, tachycardia, polyphagia, polydipsia
• Thyroid adenoma or adenocarcinoma

Primary Diabetes Mellitus in Dogs: Type I

• Insulin deficient diabetes
• Loss of B cell (lymphocytes destroy) Enzymes produced by exocrine pancreas
® Lipase and amylase
• Young-middle age
• Dependent on insulin treatment
• Autoimmune?
Diagnostic approach
1. Physical exam
a. Clinical sign – PUPD, polyphagia, polyureic, blindness when glucose infiltrate to eyes (cataracts)
b. Hepatomegaly
2. Lab abnormalities
a. Urinalysis – GLUCOSURIA, can’t concentrate urine, UTI
b. Hematology – hyperglycemia
c. Biochemistry - ­ ALT, pancreatitis, hyperlipidemia
3. IV glucose tolerance test
Monitoring diabetes
• Glucose curve
• Fructosamine

Diabetic Ketoacidosis (Diabetes General)

• Breakdown protein and fat due to starvation
• Hyperglycemia gets worse
• Ketone bodies are toxic and acidic
• Urine ketone test (test acetoacetate)

Primary Diabetes Mellitus in Cats: Type II

• Insulin resistant diabetes
• Dysfunctional B cells
• Gradual onset and non-insulin dependent for a long time
• Older age
• Hyperglycemic
• Chronic over-secretion of insulin ® co secretion of islet amyloid polypeptide ® insoluble amyloid destruct B cells
(scarring)
Glucose tolerance test
• Longer period of hyperglycemia after glucose injection
• Everything is delayed and higher ® takes longer for insulin to increase and bring down

Secondary Diabetes Mellitus

• CHO intolerance secondary to insulin antagonist (epinephrine, cortisol, glucagon, growth hormone)
• Transient diabetes mellitus that may resolve or become sub-clinical
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su

Pancreatic insulinoma
• Tumour of pancreatic beta cells ® insulin production
• Malignant
• Cause weakness and seizure
• Diagnose with fasting hypoglycemia with normal/ high insulin concentration
• Most common in ferrets
• Surgery can be curative

Pancreatic Gastrinoma
• Excessive gastrin secretion ® vomiting, diarrhea, GI ulcer, pancreatic mass
• Diagnose with basal gastrin concentration
• Poor prognosis, metastasis common

Pancreatic Glucagonoma
• Tumour of pancreatic alpha cells
• Dogs only
• Superficial necrolytic dermatitis ® breakdown of AA on skin
• See gluconeogenesis, glycogenolysis, ketogenesis

Hyperparathyroidism
• Chief cell adenoma
• Causes hypercalcemia ® very bad PTH act on:
• Soft tissue mineralization, GI abnormality, kidney disease - Bone ® resorption of Ca
• Diagnosed with persistent hypercalcemia and increased serum PTH - Intestine ® Ca absorption
• DDX ® hypercalcemia of malignancy (T- cell lymphoma and - Kidney ® Ca reabsorption
apocrine adenocarcinomal of anal gland), hypoadrenocorticism, hypervitaminosis D
• Reptiles ® secondary hyperparathyroidism from high P low Ca diet

Hypoparathyroidism
• Abrupt neuromuscular abnormalities
• Diagnosed by persistent severe hypocalcaemia and hyperphosphatemia in absence of azotemia
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Respiratory Cytology (Bienzle)
Diagnostic methods
Nasal washes and prints - Chronic discharge, nasal masses, FB
- Aggressive sampling necessary
Tracheal washes - Collection of cells in the large airways
- Cricothyroid cartilage as landmark
- Trachea normally has no leukocytes
- See: Blastomyces dermatitidis, suppurative inflammation, aspiration pneumonia
Bronchoalveolar lavage - Pass endoscope through nasopharynx to the distal bronchi
- Specific sites
- See: oslerus osleri noules, inflammation (asthma)
Alveolar macrophage
- Phagocytose mucus/RBC/carbon, recycle surfactant
Lymphocytes and neutrophils
- Immune response
- Occasion neutrophils is normal
- Predominant in suppurative inflammation
Ciliated epithelial cells
- Come from bronchi
- Viral infection if they can’t attach
Pleural fluid analysis & - Should have low leukocytes
percutaneous aspirates - Protein concentration, cell concentration
Airway diseases
Non-septic inflammatory - Indoor housing: dust, moulds, bacteria
airway disease (Heaves) - - Chronic inflammation
horses - Constricted airways, smooth muscle hyperplasia, chronic inflammation
Inflammatory airway - ­ cell concentration in BAL
disease - young horses - ­ macrophages & lymphocytes, neutrophils, +/- eosinophils, mast cells
- Excess mucus, Cough, Exercise intolerance
- No respiratory distress at rest!
Recurrent airway - Predominantly neutrophils, No toxic changes
obstruction – chronic in - Variable increase in mast cells and lymphocytes
older horses - Profound lung architectural and functional changes (not seen on BAL)
- Fibrosis
Exercise induced - Hypertension of pulmonary arteries
pulmonary hemorrhage - Caudodorsal lobes are affected
- Rupture of lung capillaries
- Contribution of IAD? Poor quality air?
- RBC outside of blood stream are INFLAMMATORY
Bacterial and viral - Pneumonia, absecess in lung and lymph nodes
infection of equine - Bacteria ® Rhodococcusequi, Streptococcus zooepidemicus, S.equi
respiratory tract – foals to - Viral ® Equine herpes virus, rhinovirus, influenza virus
yearling - Bacterial infections: suppurative +/- macrophage inflammation, organisms present ®
need to culture
- Viral infections: no specific cytological changes, fever, cough

Non-septic inflammatory - Chronic exposure to environmental allergen with predilection for inducing IL-5
airway disease - dogs and production ® eosinophil proliferation
cats - Chronic irritation from pollutants, smoke, viral infections ® IL-8 production,
suppurative inflammation, interstitial fibrosis
Allergies - dog - ­ eosinophils (BAL)
- Small airway disease - BAL
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
- Excess mucus
- Often have blood eosinophilia
Asthma - cat - brief history of illness
- Eosinophils typically predominate
- Blood eosinophilia variable
- Bronchial asthma, acute & chronic bronchitis
Parasitic airway disease - Metazoan organisms induce eosinophilic and basophilic inflammatory response with
tissue invasion
- Need for fecal examination, lung wash
Chronic bronchitis - Environmental or viral
- Small airway disease: BAL with suppurative inflammation, excess mucus production
Bacterial mycotic - Bordetella bronchiseptica:
pneumonia Infectious tracheobronchitis ® Organism adheres to cilia
- Aspergillus ® systemic
- Mycoplasma ® Immunosuppressed
- Histoplasma ® Pigeon disease
Aspiration pneumonia - Debilitated patient? Brachycephalic? Myasthenia gravis? Megaesophagus?
- Cytological hallmarks: keratinized squamous epithelial cells, mixed bacteria, plant
(feed) material
Neoplasia - Metastatic cancer
- Usually multiple lung masses unless primary
Cardio-Respiratory Pathology (Caswell)
Respiratory Pathology
Functional anatomy
- Nasal cavity and nasopharynx
o Air conduction
o Removal of large particulates
o Warming and humidification of air
o Olfaction
- Trachea, bronchi, bronchioles
o Air conduction
o Defence
- Alveoli – Gas exchange
Cells in the respiratory tract
Trachea and bronchi - Ciliated epithelial cells
- Goblet cells & submucosal glands
- Mucus and hypophase
Bronchioles - Few ciliated epithelial cells or goblet cells, no submucosal glands
- Club cells: non-ciliated cells
Alveoli - Type I pneumocytes (membranous)
o 95%
o Allow gas exchange
- Type II pneumocytes (cuboidal)
o Progenitor cells – differentiate to type I pneumonocytes
o Secrete surfactant lipids and protein
- Alveolar macrophages
o Derived forom blood monocytes
o Injest and remove inhaled particulates, recycle or degrade surfactant,
produce inflamamtory mediators
Pulmonary intravascular - Macrophages in blood vessels of: cat, horse, ruminants, pig
macrophage - But not normally in: dog, rodents, humans
- Removal of particulates from blood (bacteria, opsonized RBCs)
General pathology of the lung
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Hyperemia and - Inflammation
congestion - Presence of inflammatory cells or fibrin
Congestion - Pooling of blood in lungs
- Mild diffuse congestion is normal after death
- Left heart failure ® pulmonary congestion
Edema - Vascular permeability (bronchopneumonia)
- Reduced oncotic pressure (glomerular disease)
- Increased venous pressure (left heart failure)
- Lymphatic obstruction
Atelectasis
- Reversible collapse of alveoli without injury to alveolar septa
- Collapsed and reddened lung
- Causes airway obstruction Bronchiolar obstruction and pneumothorax disturb
Alveolar emphysema negative pressure ® cause atelectasis (obstruction
- Enlargement of alveolar airspace due to destruction of prevents ventilation of alveoli)
alveolar walls (air filled space)
- Permanent change
- Rare

Air trapped in alveolus = will resolve and return to normal

Emphysema = permeant change to the wall

Anatomic patterns of pneumonia

Pattern Gross lesion Histo Sequelae
Bronchopneumonia • Exudate in airspace • Neutrophils +/- fibrin • Infection
• Bacterial infection • +/- damage to airway or eliminated® fibrin
• Cranial ventral consolidation (except alveolar epithelium removed from
for actinobacillus which is caudal and plasmin (fibrinolysis)
primary viral pneumonia) • Infection not
• Fibrinopurulent bronchopneumonia = eliminated ®chronic
shipping fever suppurative
• Pneumonia + pleuritis = bronchopneumonia,
pleuropneumonia abscess formation,
bronchiostasis
Interstitial pneumonia • Damage to the alveolar epithelium or • Hyaline membrane •

endothelium • Type II pneumocytes

• Alveolar edema
• Can occur concurrently with
bronchopneumonia
Bronchinterstitial • Subcategory of interstitial pneumonia • Damage to the epithelium
pneumonia • Combine bronchiolar necrosis +
alveolar injury ® damage to epithelium
and exudate present in airspace
Embolic pneumonia • Pneumonia from hematogenous • •

infection
• Multifocal nodular lesions throughout
the lung
Airway disease • No specific pattern • Bronchial necrosis • Can lead to bacterial
• Damage to the bronchi and bronchioles • Less ciliated epithelial cells pneumonia
® no mucus clearance • Infiltration by
• Club cells (no-ciliated) lymphocyte,
respond to inflammation neutrophils ® airway
obstruction
• Repair
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su

On PM a thrombus in a large pulmonary artery ® due to embolism

In situ, thrombi are usually microscopic
Coughing
- Elicited by irritation/ impingement of bronchus
- Fluid leakage leading to pulmonary edema
Multilayered lung defence Summary of lung defences
1. Mucociliary clearance & cough rapidly eliminates inhaled particles - Particle entrapment
- Periciliary layer (hypophase) and mucous layer - Mucociliary clearance and cough
- Trapping of particles by mucus
- Protein in lung ® antibody and surfactant
- Clearance of mucus to the nasopharynx
2. Proteins in lung lining fluid
- Alveolar macrophages
- Block colonization, kill or opsonize bacteria that reach the lungs - Recruited cells ® neutrophil and
- Antibody lymphocytes
- Surfactant proteins A and D - Type I pneumocytes ® alveolar gas
- Defensins exchange
- Lactoferrin - Type II pneumocyte ® progenitor cells
- Lactoperoxidase
3. Alveolar macrophages
- Phagocytosis of particles & bacteria 3 predisposing causes for in situ thrombosis?
- Killing pathogens - Glomerular disease, ¯ antithrombin
- Sepsis
- Recruitment of inflammatory cells
- Corticosteroid therapy
4. Recruited cells - Vascular disease, HW, pulmonary
- “Housekeeping” in the alveoli vascular disease
- Enhance lung defences 2 sources of emboli?
- Jugular vein
- Neutrophils, macrophages: phagocytosis and killing of bacteria - Right AV valve
- Lymphocytes: activate macrophages to become better killer - Emboli from somewhere else!

Species specific patterns

Species Bronchopneumonia Interstitial Bronchinterstitial Embolic Airway
Dogs • Kennel cough • Interstitial lung • Canine distemper • Blastomycosis - • Distemper,
(bordetella disease metastatic CAV-2
bronchiseptica) (diffused/ neoplasia • Corona
• Distemper anterior) • FHV, calici
• Streptococcus (cats)
• Staphylococcus • Young cats –
• Aspiration metastrongyle
pneumonia • Liver flukes
• Pasteurella (cats) (paragonimus
kellicotti)

Cattle • Shipping fever • Lush forage in • Viral pneumonia – Metastatic • BHV-1

(Pasteurella, late summer ® BDV, Parainfluenza neoplasia (rare) or • BRSV
Mannheim tryptophan Corona, Herpes secondary • PIV-3
hemolytica, metabolism ® 3 • IBR infection ® • Corona
histophilus somni, methylendol systemic bacteria •

Mycopalsma bovis) toxicity

• IBR (w ulceration) (rubbery)
• Mycoplasma bovis • Bovine
(granulomas; mid respiratory
ear) syncytial virus
• Larval migration
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Horse • Strangles (strep • Actinobacillus • Herpes Mycoplasma felis • Heaves
equi equi) equi in foals • Hyaline membrane • EHV-1, EHV-4
• Strep • Hyaline disease & Meconium • Guttural
zooepidemicus membrane aspiration (type I pouch
• Rhodococcus equi disease in foals pneumocyte injury) mycosis
(empyema,
puss in
guttural
pouch)

Swine • Swine influenza • PRRS • PRRSV, PCV-2

• Mycoplasma • Porcine
hyopneumoniae circovirus
(pink-tan) (rubbery)
• Pasteurella, • Swine influenza
haemophilus, strep,
bordetella (purple-
red)
• Actinobacillus
Sm Lentiviral
•

ruminants pneumonia
a(maedi visna)
Bovine lungworm ® Dictyocaulus viviparus (caudal bronchi)

Pathogenesis of shipping fever

- Impair respiratory defences by infecting ciliated epithelium to ¯ mucocilliary clearance, alveolar macrophage to ¯
antibacterial function
- Mannheima hemolytica produce leikotoxin ® necrosis of macrophage and neutrophil
- Mycoplasma bovis ® also causes polyarthritis and caseonecrotic bronchopneumonia

Morphology
- Cranioventral lobar pattern ® black, purple lobules
- Fibrinopurulent exudate ® harden alveoli
- Interlobular septa distended by edema and fibrin
- Foci necrosis around

Aspiration vs. Diffuse lesion

- Vomiting ® aspiration ® bronchopneumonia
o Presence of localized lung lesion + mixed culture of enteric bacteria suggests aspiration pneumonia
o Predisposing lesions in a dog
> Megaesophagus
> Persistent right aortic arch
> Cleft palate
> Thymoma
- Reduced mucosal barrier ® septicemia ® diffuse lesion
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Pathogenesis of airway obstruction
- Bronchoconstriction ® edema ® necrotic cells fill lumen

Disease Characteristics Cause

Hydrothorax - Edema of pleural space - Heart failure: increased venous pressure
- Clear filled (transudate) - Hypoproteinemia: reduced oncotic pressure
- Lung compression - Lymphatic obstruction
Chylothorax - Milky pleural fluid, rich in triglyceride - Heart failure: Increased central venous pressure
and lymphocytes, represents loss of prevents drainage of lymph from the thoracic
lymph fluid into the pleural space duct into the vena cava.
- Many cases are idiopathic.
- Uncommonly due to obstruction of the thoracic
duct by tumours or other
- Cat with HCM
Pyothorax - Neutrophils - Cat with HCM
Hemothorax - Blood in the cavity - Trauma (eg. fractured ribs),
- Ruptured tumours (especially hemangio-
sarcoma)
- Anticoagulant rodenticide toxicity, and thymic
hemorrhage syndrome in young dogs
Pleuritis - Inflammation - Bacteria via 3 routes – external penetrating injury,
- Usually, bacterial extension from bacterial pneumonia or ruptured
lung abscess, hematogenous spread
- Penetrating injury (dogs)
- Histophillis somni
- FIP (cats)
Pleural - Respiratory distress - Tumour invade the pleura and spread
neoplasm - Pulmonary adenoma
- Meothelioma
Pneumothorax - Air in the pleural space - Incision of diaphragm
- Atelectasis of lung
- Penetrating wound
- Rupture of pulmonary bulla

3 ways bacteria enter pleural cavity

- Hematogenous
- External injury (trauma)
- Underlying lesion
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Cardiovascular Pathology
Disease of the endocardium
Endocardiosis: degenerative lesion
Disease Myxomatous mitral valve disease
Cause Chronic degeneration of the valve (common)
Lesion Shiny smooth-surfaced nodules
Diagnosis Sudden death
Rupture of chordae tendinae
Myocardial ischemia (underperfusion of myocardium)
Hemopericardium, hemorrhage
Sequelae Valvular incompetence
Cardiomegaly (left sided, myocardial hypertrophy, eccentric (dilation of chamber))
Left atrial rupture
Heart failure ® gongested lung

Pathogenesis
Valve disease ® regurgitation ® atrial dilation ® rupture ® hemopericardium
Endocarditis:
Disease Valvular endocarditis
Cause Bacteremia, thrombosis and neutrophil infiltration
Lesion Thickened focal heart valve with vegetation, dull surface, fibrin and neutrophil covered
Diagnosis Neutrophil and fibrin on valve
Lesion can grow into mass that protrudes
Rough irregular surface
Sequelae Heart failure due to valvular incompetence or stenosis
Thromboembolism to lungs (from right side)
or kidney and myocardium (left side)
Pulmonary edema (left side) and ascites (right side)
Septic emboli
Dilation of the atrium
Heart Failure
- Left sided
o Left AV valve or aortic valve lesion ® endocardiosis, endocarditis
o Myocardial disease ® cardiomyopathy, myocardial necrosis, myocarditis
o Cardiac anomalies ® SAS, PDA, VSD
- Right sided
o Right AV valve or pulmonic valve lesions ® endocardiosis, endocarditis
o Cor pulmonale due to ­ resistance to pulmonary blood flow
o Consequences of left heart failure
Pathogenesis of heart failure
¯ CO ­renal blood flow ctivation of RAS system ® sodium and water retention ® leading to:
• Peripheral edema
• ­ blood volume and exacerbates heart failure
• ¯ pulmonary blood flow ® hypoxemia
• ­ erythropoiesis ® polycythemia
¯ blood flow to heart via coronary arteries ® myocardial ischemia
Inability to move Left sided congestive heart failure
venous blood forward - Left atrial dilation
- Pulmonary congestion and edema
- Hemosiderin-laden macrophage in pulmonary alveoli (heart failure cells)
- Hydrothorax
- Hemosiderin
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Right sided congestive heart failure
- Subcutaneous edema, ascites (in cats), hydrothorax
- Hepatomegaly
- Nut meg liver in cattle and dogs (fibrosis, necrosis, fatty degeneration, congestion)

Disease of the myocardium

HCM
Disease Cardiac hypertrophy (diastolic failure)
Cause Increase workload
Lesion Eccentric hypertrophy: increase myocardial mass with dilated lumen (volume overload)
- Shunt or leaky valve ® volume overload ® eccentric hypertrophy
Concentric hypertrophy: increased myocardial mass with a small lumen (pressure overload, subaortic
stenosis)
- Stenosis of outflow tract ® pressure overload ® concentric hypertrophy
Diagnosis Gross
- Left ventricular hypertrophy should beL:R > 3:1, diseased HCM 5:1
- Increased heart weight (normal 5.8 (2.8-8.8) g/kg
- Left atrial dilation, if heart failure
- ± Obstruction of aortic outflow tract
Histo
- Myocardial fibrosis
- ± Fatty replacement of myofibres
- ± Myofibre disarray
Sequelae - Inadequate perfusion of myocardium
- Increase myocardial oxygen consumption
- Compromised efficient laminar flow of blood within the ventricle, inefficient turbulent flow
- ¯ cardiac output and turbulent flow ® saddle thrombus
ARVC
Disease Restrictive cardiomyopathy
Cause Arrhythmogenic right ventricular cardiomyopathy in boxer dogs and cats
Lesion Myocardial fibrosis and replacement of myofibers with adipocytes
Diagnosis Gross
- normal, or right ventricular dilation
Histo
- right ventricular fibrosis & fatty replacement
Sequelae Sudden death, due to arrhythmia; syncope, right heart failure
RCM
Disease Restrictive cardiomyopathy in Cats
Cause Like HCM but no concentric hypertrophy
Lesion Myocardial fibrosis or endocardial fibrosis
Diagnosis Dilation of left atrium (+/- RA)
Endocardium thickened/ fibrosis
Ventricle not thickened or dilated
Sequelae Restricted filling during diastole on echo
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
DCM
Disease Dilated cardiomyopathy (DCM) (systolic failure)
Cause Idiopathic (primary in certain breeds of dogs)
Myocardial necrosis, inflammation, unknown
Volume overload from MMVD or shunt (PDA, VSD)
Diet deficiency of taurine
Monensin
Lesion Both ventricles and atria usually dilated
Thinned ventricular walls
Endocardium diffusely thickened and white
Diagnosis Gross
- Increased weight of heart
- Valve lesions or myocarditis or necrosis
Histo
- Variation in myofiber size and interstitial fibrosis
Sequelae Unable to contract during systole
Myocardial Necrosis
White muscle disease - Deficiency in vitamin E and selenium
- Myocardial or skeletal muscle necrosis
- Mineralization
Mulberry heart disease of pigs - Multifocal or diffuse myocardial hemorrhage ® fibrinous pericarditis
(strep suis septicemia can appear identical)
- Hyaline degeneration or fibrinoid necrosis of myocardial arteriole and
necrosis of cardiac myofibres (histo)
Myocardial toxins - Monensins/ ionophores ® soft patchy area of pallor
- Doxorubicin
Ischemic necrosis - Reduced myocardial perfusion
- Thrombosis of coronoary arteries
- Excessive cardiac hypertrophy
Capture myopathy - Overworked myofibres
Myocardial Infection and inflammation
Histophilus somni - Myocarditis in feedlot cattle
- Acute onset of left heart failure
- Focal area of coagulation necrosis or abscessation of left ventricular
papillary muscle
- Pulmonary edema
- Microaerophilic pathogen
- Focal necrosis
Clostridial myositis – blackleg - Clostridium chauvoei
- Heart or skeletal muscle
- Focal red-black dry lesion
- Fibrinous pericarditis
Suppurative myocarditis - Any species due to bacteremia
Lymphocytic myocarditis - Rare and no gross lesions
- Caused by toxoplasmosis, canine parvovirus (in neonates), BVDV in calves,
foot and mouth disease
- Histopathology to diagnose
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Disease of the pericardium
Hydropericardium
- Fluid in pericardial sac; transudate
- Causes are similar to those of edem: congestive heart failure, hypoproteinemia
- Usually does not impair heart function unless fluid accumulates very rapidly
Hemopericardium
- Accumulation of blood in pericardial sac
- Cause
o Rupture right atrial hemangiosarcoma, ruptured left atrium secondary to mitral valve disease, rupture
base of aorta in horse
o Anticoagulant rodenticide toxicity
o Trauma
- Could lead to cardiac tamponade and right heart failure (fail to fill during diastole)
o Pericardial fluid or fibrosis ® prevent filling ot heart during diastole ® right side failure
Pericarditis
- Cause
o Blood-born spread (bacteremia)
> E. coli septicemia in neonates
> Streptococcus suis and histophillus parasuis (glasser’s disease) (pig)
o Penetrating wound
> Hardware disease
o Myocardial abscess rupture
o Blackleg (clostridium chauvoei) (cattle)

Pathology of the blood vessels

Arterosclerosis*
- Fibrosis of tunica intima of arteries
- ¯ elasticity and narrowing of lumen
- Often incidental
Atheriosclerosis
- Deposition of lipid in the wall of larger arteries
- Rare in domestica animals
- Caused by hypothyroidism ® hypercholesterolemia ® lipid metabolism altered
Arterial and endocardial mineralization
- “Metastatic”
o Vitamin D toxicity – Johne’s disease
- “Dystrophic”
o Vascular injury of many causes

Heart dissection
1. Cut off apex
2. Start at right auricle ® open up whole atrium
3. Continue down the right AV valve (tricuspid)
4. Cut up pulmonic valve and out the pulmonary
artery
5. Cut at left auricle across left atrium
6. Cut down left AV valve (mitral)
7. Cut up aortic valve to aorta
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Laboratory Evaluations of the Renal System (Beeler-Marfisi)
Laboratory Tests
- Serum
o Urea
> Azotemia = ­ nitrogen waste
o Creatinine
> 100% should goes in urine
> Created by muscle tissue at a steady state
o Phosphorus
o SDMA
> 100% should go in urine and produced at a steady state
> More sensitive than creatinine
o Potassium
o Albumin
- Urine
o Urinalysis
> Gross evaluation; dipstick; micro evaluation
> Urine protein: urine creatinine ratio
® Locates area that is leaking (glomerulus or tubule)
Diagnosis of Kidney Disease
Chronic Kidney Disease Acute Kidney Injury/ Disease
- Anemic: Mild normocytic normochromic - Not anemic
- Electrolytes stable, potassium normal or ¯ - Electrolyte imbalance: ­­ Potassium
- Poor body condition - Oliguric/ anuria
- May have uremia ® stomatitis, neuro sign, - ­ SDMA, creatinine, urea abruptly
GI upset, CVS sign - Azotemia
- Toxciants
- ¯ GFR hallmarks:
o SDMA, urea, creatinine will ­
- PLN hallmarks:
o Proteinuria
o ¯ albumin
- Pre-renal urea increased due to:
1. Carnivorous diet Glomerular filtration = SDMA, urea,
2. ­ Endogenous protein catabolism creatinine
3. Ruminant vagal indigestion ® rumen stasis, ¯ GFR
- ¯ Urea due to: Collecting duct = USG
1. Liver failure Horse/ Cattle= 1.025
2. Portosystemic shunt Dog = 1.030
3. ¯ water resorption in tubules (eg. diabetes) Cat = 1.035
4. Protein malnutrition (TMR lacking)
5. Loss in caudal GIT in horses
- Pre-renal creatinine increased due to
o Expected in well-muscled individuals
- ¯ Creatinine due to:
1. Young animal
2. Muscle atrophy (older animal)
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Interpretations
Azotemia and USG
Status Parameters
Kidney failure - Azotemia + isosthenuria (USG 1.008-1.012)
- Unable to concentrate urine, especially if dehydrated
Need further assessment and - Isosthenuria but not azotemic
know hydration status - Maybe they were given fluids
- Must repeat
Obstruction / blockage - Post renal azotemia
- Feline lower urinary tract disease
- USG appropriate initially ® want to avoid rupture/ hydronephrosis
Proteinuria
Type Reason
Pre-renal - Increased protein in blood
- Physiological (fever/ exercise), hypertension (heart disease), multiple myeloma
- Hemoglobinuria due to red cell lysis ® IMHA, copper toxicity, Heinz body anemia
- Colostrum
Renal - Glomerular proteinuria: Charge and filter altered, see hypoalbunemia on biochemistry
- Tubular proteinuria: glomerulus is fine, normal albumin on biochemistry.
Acute or congenital kidney disease, transport protein not working (Fanconi’s
syndrome), gentamicin acute kidney injury, proximal tubule damage
Post-renal - Hemorrhagic/ inflammation
- Renal or bladder calculi
- Toxin ® nwarfarin
- Trauma, neoplasm
UPCR
- When you have low albumin but normal globulin ® run this test
- Proteinuria between 0.2-2.0 ® tubular or glomerular
- Proteinuria >2.0 ® glomerular (severe)
Clinical term USG Range
- Healthy = <0.2
- When abnormal – come back to trend in 2-4 weeks Hyposthenuria <1.008
- Borderline – come back in 2 months Isosthenuria 1.008-1.012
USG
Minimally concentrated 1.013-1.030 (dogs)
- Polyuria and isosthenuria from kidney urine 1.013-1.040 (cats)
o 2/3 nephron damage
o Acute kidney injury Hypersthenuria >1035 (dogs)
o Chronic kidney disease >1.045 (cats)
- Isosthenuria due to others
o Diuresis/ endocrine/ drugs
o Medullary washout
Nephrotic syndrome
o Hypercalcemia
o Fanconi syndrome - Protein losing nephropathy leading
- Hyposthenuria to abdominal transudation
o Body is actively getting rid of water - Hypoabuminemia
o Diabetes - Hypercholesterolemia
- Edema
- Hypercoagulabel state (loss of
antithrombin)
 VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Urinalysis (Beeler-Marfisi)
Complete urinalysis
1. Gross assessment
- Colour
- Turbidity ® spin down, cells cast, crystals (things that can’t dissolve)
2. USG
- Anything that dissolve ® ions, protein and molecules
- Ignore dipstick USG
3. Chemical evaluation
- Glucose (30s) - Blood
o Not present tin health o Reaction to iron ® positive reaction
o Normal in puppies up to 8 weeks that indicate myoglobin, hemoglobin,
(immature tubules) RBC lysis
- Bilirubin (30s) o False negative ® ascorbic acid
o Expect bilirubinuria before bilirubinemia o False positive ® bleach
o If normal USG then its ok to get 1+ in - pH (60s)
DOGS o Dog, cat, herbivores on milk ® 5.5-7.5
o DDX o Herbivore ® 7.0-8.5
> Liver disease o Alkaline pH
> Bile duct obstruction > UTI (proteus, staph, ureases)
> Hemolysis > Low protein diet
> Starvation > Respiratory or metabolic
> Pyrexia alkalosis
> *Horses OFF feed ® 12-24 hr of > Crystal
fast* o Acidic pH
> Cats with DM or > Glucocorticoid
hyperthyroidism > Protein catabolism
o False negatives due to ® aged sample, > Furosemide
ascorbic acid, light exposure > Renal tubular, metabolic
- Ketone acidosis
o Detection of acetoacetic acid & acetone > Hypochloremia metabolic
(not B-OHB which is done in blood test) alkalosis ® DISPLACED
o Expect ketonuria before ketonemia abomasum
o DDX - Protein (60s)
> Negative energy balance o Detects albumin (negative charge)
> Diabetic ketoacidosis o Confirm with sulfosalicylic acid
> Insulinoma turbidimetric test

4. Microscopic examination of sediment

- Urine sediment preparation ® spin down and pipette leaving 10% of starting volume
- 10x power field (LPF): Squamous epithelial cells and casts
o <2 fine granular or hyaline casts = OK
Red urine ® spin it down to see why it is red
o Absence of cast does not rule out kidney
disease Hematuria - Pallet at the bottom + clear urine
- 40x power field (HPW): WBC, RBC, Epithelial cell, Intravascular - PCV decreased
Crystal, Bacteria hemolysis - Plasma is pink
o Well concentrated urine + <5 WBC or Myoglobinuria - Normal PCV
RBC = OK
o >5 WBC = NOT GOOD - Clear plasma
o Isosthenuria + WBC + RBC = NOT GOOD - AST & CK ­ (muscle trauma)
o No bacteria doesn’t mean no infection
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Crystalluria
Common crystals Uncommon crystals
- Struvite - Calcium oxalate monohydrate
- Bilirubin - Ammonium biurate
- Calcium carbonate - Cystine
- Amorphous - Drug crystals
- Calcium oxalate dihydrate

- Cat and dog with alkalinuria

Struvite - Associated w urease-producing bacteria
- Looks parallel, headless guy going yay!

- Lightbulb appearance
- Orange, round
`Bilirubin - Normal especially with well concentrated
urine
- Can have babesia canis adherent ®
intravascular hemolysis

- Normal in: horse, guinea pig, rabbits

Calcium
- Looks like 2 pompoms stuck together
carbonate
- Greenish pink at edge

Amorphous - Low numbers in healthy dogs

calcium or - Alkalinuria
phosphate -

Calcium
- Normal in: dogs, cats, horses
oxalate
dihydrate - Diamond

Calcium - BAD
oxalate - Ethylene glycol intoxication
monohydrate - Looks like double ended picket fence

- Suggest liver dysfunction or PSS

Ammonium
- Common in Dalmatian and English bulldogs
biurate
- ­ammonia, ­bile acid, ¯ urea
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
- 6 flat sides
- Inherited defect in renal tubular transport of
Cystine AA cystine
crystals - Androgen responsive in males
- Form uroliths repeatedly
- Bad for males

- Common in TMS
Drug crystals
- Unequal pompoms

Casts
- Counted as number/ LPF (10x)
- Normal <2/ LPF in concentrated urine

- Abnormal when >2/ LPF

- Glomerular disease
Hyaline casts
- Rounded end, parallel smooth side
- Easier to see stained

Fine granular
- Abnormal when >2/LPF
cast

- Epithelial
- Fatty
- RBC
- WBC
- Waxy
Abnormal
casts
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Urinary Pathology (Lillie)
Lower urinary tract Diseases
- Function
o Urination
o Keep pathogen out (vesicoureteral valve)
- Disruption of urination
o Obstruction
> Urolithiasis
> Congenital anomalies, inflammation, neoplasia
o Upstream dilation
> Hydronephrosis, hydroureter, hydrourethra, bladder rupture
- Predisposing factors to disease
o High levels of calculogenic material
o Urine pH
o ¯ water intake
Common Stones
Dogs Cat Cow Sheep Horse
Struvite Struvite Silica Silica Carbonate
Oxalate Oxalate Struvite Struvite
Purines (urate/ uric Carbonate Oxalate
acid, xanthine) Clover stone
Cystine Carbonate

Struvite urolith Urate

- Magnesium ammonium phosphate hexahydrate - Dalmatians
- Infection stone ® female > male - Ammonium biurate stone in PSS dogs
- White, chalky - Green-brown
- Less soluble at ­ pH Xanthine
- Cats and cows - Dog > sheep, cattle
- Hereditary deficiency in xanthine oxidase
Silica urolith - Yellow-red
- Ruminant > dog > horse Cystine
- Dogs ® GSD, old English sheep dogs - Dogs
- Newfies
- Yellow-brown, waxy

Obstruction
- Sites
o Dogs: proximal end of the os penis Predisposing factors to disease
o Cats: anywhere - High levels of calculogenic
- Partial obstruction material
o Hydronephrosis - Urine pH
- Complete obstruction - ¯ water intake
o Rupture
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Cystitis
- Defense
o Tamm-horsfall mucoprotein, IgA, IgG, GAG, oligosaccharides ® prevent adhesion
o Acidic urine in cats and dogs
o Phagocytosis via mucosal urothelial cells
o Urothelium
o Flow
- Offense
o Urinary stasis / obstruction
o Trauma of epithelium ® urolith, catheter, chemical, diabetes
o Cystocentesis
- Causes of cystitis
o Ascending bacteria, (rectal + cutaneous)
> Uropathogenic E.coli
> Proteus vulgaris
> Strep and stap
o Species specific pathogens
> Cattle – Corynebacterium renale
> Pigs – actinobaculum suis (alkaline environment, leading cause of death in sows)
- Pathology
o Red, inflamed
o Diffused or multifocal
o Thickened
o Altered valve function
Neoplasia
- Cow, dogs cats
- Urothelial cell carcinoma
o Invasive and malignant
- Botryoid rhabdomyosarcoma
o Stromal tumour
o Benign
o Young animals, big dogs, female> male
o Spindle shaped cell/ muscle striations on hiso
Bovine enzootic hematuria
- Braken fern
- Cause benign and malignant tumours
- Toxic compounds and ventral bladder pooling
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Kidney Diseases
- 0.5% BW; 25% crdiac output; 10% O2 consumption
- End artery system Ratio of cortex: medulla ® 1:2 or 1:3
Hydronephrosis - Capsule does not expand
- Dilation of kidney via urine
- Especially medulla
- Pressure atrophy
- Unilateral ® can get far before you find it
- Bilateral ® easily see clinically

Juvenile nephropathy - Congenital/ hereditary

(renal anomaly) - Uremia at 6 mos
Renal dysplasia - Abnormal structures
o Blind ended collecting duct
o Atypical tubular epithelium
o Primitive duct
- Inappropriate structures
- Hypoplasia, aplasia
- Ureteral abnormalities
Renal cysts - 3 mechanisms
o Obstructive
o Altered tubular basement membrane
o Disorder of tubular epithelial cells
- Polycystic kidney disease
o PKD1 mutation in persians
o +/- hepatic and pancreatic cysts
o Bilateral convoluted tubules expand ® renal failure
- ARPKD – cairns, westies, sheep, persians
- CPKD – all domestic species, fatal
Medullary necrosis - Most blood goes to the cortex (prostaglandin regulated)
- NSAIDs (COX 1 inhibitor) can cause hypoxia
Papillary necrosis - Acute papillary necrosis ® hematuria, proteinuria, casts, oliguria
Infarct - Septic emboli
o Bacteria obstruction
- Wedge shaped
o Accurate or interlobular artery
Renal neoplasia - Carcinoma ® horse, cow, dogs (male>female)
- Nephroblastoma ® chickens, pig
- Lymphoma ® cats (diffused or multinodular white)

Glomerular Diseases
- 2 basic needs of kidney
o Adequate inflow (perfusion)
o Adequate functional mass (GFR)
o Adequate outflow (no obstruction)
- Glomerular filter
o By size and charge
o Endothelium ® fenestrated with anionic coat
o Basement membrane ® fenestrated with anionic coat
o Epithelium ® anionic and filtration slit
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
Glomerulonephritis
- Types: (clinically the same and drift toward glomerulosclerosis)
a) Membranous – cats “Proteinuria, occurring in the
b) Proliferative absence of urinary tract
c) Membranoproliferative – dogs, horse, ruminants inflammation, is suggestive of
d) Glomerulosclerotic glomerular damage”
- Proteinuria in the absence of UTI = glomerular damage
- Pathogenesis
o Circulating antigen-antibody immune complex
o Deposition in subendothelial, subepithelial, intramembranous
o Chronic ® fibrosis and scarring
Amyloidosis Outcome of massive
proteinuria
- Massive proteinuria without fibrosis
- Thrombosis ® LOSS of
- Amyloid deposit in glomeruli ® thrombosis and hepatic failure
antithrombin III and
- Reactive amyloidosis plasminogen activator
- Damage via pressure atrophy caused by amyloid deposition - Nephrotic syndrome
- Common in older dogs - Hypoproteinemia/
- Hypercoagulable hypoalbuminemia
Embolic nephritis - Hyperlipidemia
- Small emboli ® single/multiple abscess - Edema
- Large emboli ® infarct, abscess
- Agents
o Actinobacillus equuli (foals)
o Eysipelothrix (pigs)
o Truperella ypogenes (cattle)
o E. coli (calves)
o Corynebacterium pseudotuberculosis (sheep)
- Appearance
o Gross: White spots w hyperaemia = WBC or tumour
o Histo: Blue = bacteria and inflammatory cells

Tubules Diseases
Acute renal failure
- 75% loss of function
- ­ K ® cardiotoxic, pulmonary edema, metabolic acidosis
1. Acute tubular necrosis (Toxin, bacteria, virus, drugs) Interstitial nephritis agents
- Acute tubular necrosis Horse Equine viral arteritis
o Due to Cattle White spotted kidney
> Hypoxemia, anemia Leptospira interrogans
o PCT is most susceptible (due to ­ metabolic rate (canicola)
o Macroscopic lesions minimal MCF
- Ethylene glycol toxicity Sheep Sheepox
o Peracutely: neurological disease and acidosis Pigs Leptospira (Pomona)
o Tubular necrosis with crystals PRRS
o Metabolite is toxic (glycoaldehyde, glycoxylate) Dogs Leptospira (canicola), CHV-1
- Hemoglobinuric nephrosis
o Dark black kidney
o Due to
> Copper toxicosis in sheep
> IMHA in dogs
> Red maple in horses
VETM* 4490 Systems Pathology Exam Summary Notes Jolin Su
- Interstitial nephritis (due to infectious causes)
o Leptospirosis
> Appears to be multifocal
o E. Coli/ White spotted kidney
> Calves
> Common, incidental
- Granulomatous
o FIP in cats Urinary tract is normally
> Resembles lymphoma sterile
o Harry vetch toxicosis plant (Prussic acid)
> Lesion follows blood vessel, could be cryptococcus as well Vesicoureteral calve ®
2. Obstruction compromised in obstruction
3. Ischemia (Vasculitis, emboli) which ­ reflux
- Patchy focal tubular necrosis
- Damage of both basement membrane and epithelial cells lead to scarring

Acute Pyelonephritis
- NB endotoxin (gram negative) can inhibit normal ureteral peristalsis ® bacteria can make it up to kidney
- See fibrosis due to chronic inflammation
- Unlike infarcts the lesion goes all the way from cortex to medulla
o Medulla is highly susceptible to bacterial infection
o A poor blood supplies Pathology:
o ­ NH3 inhibits complement activation Pelvis and ureters are inflamed, papilla
- Etiology and medulla are necrotic and eroded,
o Cystitis especially at renal poles. Pus in kidney
o Rectal flora (E. coli, especially cats)
o Corynebacterium renale (cows)
o Actinobaculum wuis
Metastatic mineralization
- Calcium phosphorus imbalance ® precipitate
- Alkaline pH in tissue
- Especially subpleural in dogs
Uremia
- Clinical syndrome
- ¯GFR filtration ® elevation of blood urea and creatine
- Multisystemic disease
o Hyperkalemia, acidosis, pulmonary edema
o Ulcerative glossitis
o ALWAYS Azotemic
- Changes
Uremic glossitis Oral ulcer and necrotic stomatitis
Local vasculopathy or direct toxicosis of ammonia
Uremic gastropathy Ulcerative and hemorrhage necrotic gastritis
Horse and cattle get ulcerative and hemorrhage colitis
Ischemia, vasculopathy
Uremic pneumopathy Pulmonary edema and mineralization
Pulmonary, atrial, aortic thrombosis Damage to endothelium and severe protein loss ® loss of
antithrombin III and plasminogen activator in urine
Pericarditis Fibrinous
Tissue mineralization (dogs) Pericardium, soft tissue, artery
Ionized calcium and phosphorus precipitate