Exam 2 Flashcards
Path of O2 in airway
o Alveolar Epithelium ->
o Fused basement membranes ->
o Capillary endothelium ->
o CO2 goes in reverse (20x more diffusible than O2)
Normal Structure Alveolar epithelium
Pneumocytes o Type 1: • Squamous • little repaire • no regen o Type 2: • Cuboidal, microvilli • Can regen • Produce surfactant
Normal structure bronchioles
o Clara cells act as stem cells
o Used for enzymatic detox
Nutritional Vs Functional blood supply in lungs
o Functional
• From R heart for gas exchange
o Nutritional
• From L heart to interstitial tissue in lungs
Ventilation / perfusion mismatch
o Blood & air are not getting to same place
o Due to block of blood supply or block of airway
Acid Base Balance in lungs
Respiratory alkalosis
• due to HYPERventilation = blow off CO2
Respiratory Acidosis
• due to HYPOventilation = too much CO2
Metabolic Acidosis
• Respiratory compensation: HYPERventilation
Metabolic Alkalosis
• Respiratory compensation: HYPOventilation
Define: tachypnea, dyspnea, cyanosis, hemoptysis, epistaxis, stridor, stertor
o Tachypnea- rapid breathing o Dyspnea - labored breathing o Cyanosis - blue skin due to decreased blood O2 or circulation o Hemoptysis – coughing blood o Epistaxis – nose bleed o Stridor - harsh grating sound o Stertor - snoring
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3 Routes of entry of organisms into lungs, & natural defenses for those routes
Inhalation (airborne) • Sneezing, coughing, bronchoconstriction • Mucociliary clearance • Phagocytosis by alveolar macrophages • Hyperplasia = chronic resp Dz
Hematogenous (blood borne)
• Intravascular macrophages
Direct Extension (penetrating)
Primary Ciliary Dyskinesia
o Genetic defect in ciliary morphology ->
o Defective ciliary movement ->
o Defective mucociliary clearance ->
o Predisposition to infection
Defenses against blood-borne respiratory agents in dogs & rodents Vs ruminants, cats, pigs, horses
Dogs, rodents, humans
• phagocytosed by Kupffer cells and splenic macrophages
ruminants, cats, pigs, horses
• pulmonary intravascular macrophages
4 Main Causes of Impairment of Respiratory Defenses
Viral:
• Destruction of cilia,
• impaired pulmonary alveolar macrophage function
• often predisposes to bacterial infection
Bacterial:
• Inhibit cilia,
• survival and replication in macrophages
• can predispose to other bacteria
Toxic gasses:
• Direct injury to tracheal/bronchial epithelial cells and pneumocytes
Immunodeficiency:
• not very common
Cellular Response to Acute & Chronic Mucosal Damage in Respiratory Tract
Acute Mucosal damage:
• Decreased cilia + increased goblet cells
• Inflammation - hyperemia, edema, neutrophils
• Impaired mucociliary clearance
• Ciliated epithelium will repair IF basement membrane is intact or scar if not
Chronic Mucosal Damage • Goblet cell hyperplasia • Fibrosis • Squamous metaplasia • Decreased clearance and increased airway resistance
Cellular Response to Smooth Muscle, Alveoli, & Interstitium Damage in Respiratory System
Smooth Muscle
• Hyperplasia/hypertrophy of smooth muscle = increased airway resistance
Alveoli
• Type II pneumocyte hyperplasia = reduced gas exchange
Interstitium
• Interstitial fibrosis = reduced ventilation of alveoli
Developmental Abnormalities of the nasal cavity & sinuses
brachycephalic dogs:
• Noisy inspiration
• May have obstruction w/ cyanosis and collapse during exercise
• Elongation of soft palate causing obstruction of glottis -> increased inspiratory effort.
Cleft palate
• Milk and food from nostrils = sneezing, nasal discharge
• Associated with aspiration pneumonia.
Atrophic Rhinitis: predisposing factors, offending agents, pathogenesis
Predisposing factors: • infectious (bacteria +/- viral), • environment, • genetics, • nutrition
Agent
• Bordatella bronchiseptica + Pastuerella multocida
Pathogenesis:
• Toxins from Pasteurella stimulate osteoclasts & inhibit osteoblasts -> degeneration and remodeling of nasal turbinates
Epistaxis: 3 places it may originate & causes
Blood may originate from w/in nasal cavity
• Causes: Trauma, inflammation, ethmoid hematoma
Blood may originate distal to the nasal cavity
• Causes: Guttural pouch mycosis, neoplasia, pneumonia, exercise-induced pulmonary hemorrhage in horses
Blood may not necessarily be due to local disease
• Causes: Platelet / coagulation defects
Nasal Cavity Neoplasias: most common types in dogs, cats, & sheep
Most common in dogs & most are malignant
• nasal carcinoma/adenocarcinoma
Cats
• squamous cell carcinoma, lymphoma
Sheep
• Enzootic nasal carcinoma (retrovirus)
Non-neoplastic Nodules in Nasal Cavity
- Nasal polyps (cat/horse)
* Cysts (horse)
Equine pharyngeal lymphoid hyperplasia: basics, signs, gross lesions, histo
- Most common cause of partial upper airway obstruction in horses (esp 2-3 yr old racehorses, 30- 60%)
- Regress with age
- Etiology unknown: likely chronic bacteria + environment
Signs
• Stridor, changes in voice, dysphagia, cough, dyspnea in severe cases
Gross Lesions
• White foci in dorsolateral pharynx
Histo
• Lymphoidnodules
Brachycephalic airway syndrome
- Stenotic nare and elongated soft palate -> laryngeal edema
- Can have severe upper airway obstruction
- Common in Bulldogs, boxers, boston terriers, pugs, Pekinese
- Signs: Sturdor (snoring), exercise intolerance, +/- severe dyspnea, cyanosis
Necrotic Laryngitis
- Aka laryngeal necrobacillosis or calf diphtheria
- Calves: damage to laryngeal mucosa (feed, balling gun) - > Secondary bacterial infection -> Local inflammation/necrosis, risk of pneumonia, risk of local airway obstruction
Laryngeal hemiplagia
• AKA roaring
Horses
• Atrophy of dorsal and lateral cricoarytenoid muscles
• Denervation due to primary or secondary disease of left recurrent laryngeal nerve -> affects L side
Dogs
• Laryngeal paralysis
Neoplasia affecting pharynx/larynx
Dogs: very rare tonsilar squamous cell carcinoma
Issues w/ guttural pouch
Guttural pouch Tympany
• distention with fluid and gas
Guttural Pouch Empyema
• distention with purulent exudate
Guttural pouch Mycosis
• fungal infection
Guttural Pouch Mycosis: entry, lesion, signs
- fungal infection
- Most common problem with the guttural pouch
- Usually unilateral
Entry
o Inhalation of mold spores from feed/environment
Lesion
o Fibrinonecrotic exudate- necrosis and inflammation
Signs
o Epistaxis- Unilateral or bilateral, acute or intermittent
o Nerve damage
Disease & Other Causes of inflammation in trachea
- Canine Infectious tracheobronchitis
- Herpes viruses - Infectious Bovine Rhinotracheitis, Equine Rhinopneumonitis
- Secondary to collapsing trachea, other trauma
Signs of tracheal inflammation
- Non-productive honking cough
* Obstruction (in birds)
Tracheal anomalies
- Agenesis
* Hypoplasia (bulldogs)
Tracheal collapse: cause & signs
- Wide dorsal tracheal membrane
- Small breed dogs
Causes:
• Trauma, obesity, masses may exacerbate
Signs • Dry, honking cough • Dyspnea (worse with stress/exercise) • Cyanosis • +/- secondary pneumonia
Restrictive Respiratory Failure
- Pathology that results in restriction of inflation of the lungs
- Intrapulmonary
- extrapulmonary
Pathophysiology • Restriction of lung inflation limits ventilation -> • Low O2 Normal CO2 -> • Rapid, shallow respirations -> • Low CO2 -> • respiratory alkalosis
Intrapulmonary Restrictive Respiratory Failure
Lesions in alveolar and interlobular septa o Interstitial edema o Interstitial pneumonia o Alveolar Fibrosis o Type II pneumocyte hyperplasia
• Effect is less compliant walls
Extrapulmonary Restrictive Respiratory Failure
Lesions in pleural cavity, mediastinum, thoracic wall
o Pleural effusion (fluid in pleural cavity)
o Pneumothorax
(air in pleural cavity)
o Deformities (or masses)
Obstructive Respiratory Failure: pathophysiology & mechanisms
• Pathology that results in reduced ventilation of the lungs
Pathophysiology • Obstruction of air flow in lungs reduces ventilation -> • Low O2 & High CO2 -> • Rapid/deep respiration -> • Low O2 High CO2 -> • respiratory acidosis
Mechanisms
• Obstruction of movement of air in airways or alveoli
• Exudative pneumonia- exudates fill alveoli
• Pulmonary edema – edema in alveoli
• Bronchitis or bronchiolitis- exudates, mucous, hyperplastic epithelium obstructs airways
Recurrent Airway Obstruction (RAO, Heaves)
- Horses
- Likely allergic
- Diffuse bronchiolitis - epithelial hyperplasia, mucous
Signs o Cough o Tachypnea o Wheeze o Exercise intolerance o Dyspnea- Expiratory -> “heave line” o Weight loss
Feline Asthma: pathogenesis, respiratory signs, other signs
Pathogenesis
o Obstruction of small airways
->
o Bronchiolar smooth muscle hyperplasia and constriction
o Hypertrophy/hyperplasia of mucous glands
Respiratory signs
o Normal at rest
o Coughing to severe respiratory distress when stressed
o Lung sounds normal to crackles and wheezes
Other signs:
o Anorexia, weight loss
o Peripheral eosinophilia in 30%
Pulmonary Edema: Pathogenesis & mechanisms
Pathogenesis:
• Fluid accumulates in the interstitium restricts lung inflation
for variable length of time
->
• Fluid in alveoli occurs abruptly
->
• Increased rate and depth of respiration
->
• Loud lung sounds initially (quiet with severe edema)
Mechanisms
• Increased permeability
• Increased hydrostatic pressure or Decreased oncotic pressure
• Impaired lymphatic drainage
Increased Permeability leading to pulmonary edema
- cytokines -> inflammation ->
- damage to pneumocytes & endothelium ->
- leaky vessels -> high protein fluid
Hemodynamics of pulmonary edema
Increased Hydrostatic Pressure
o Left heart failure - cardiogenic edema
o Hypervolemia/fluid overload
Decreased Oncotic Pressure
o Hypoalbuminemia
Impaired Lymphatic drainage in pulmonary edema
- Least common mechanism
* Neoplasia blocking lymphatics
Acute Respiratory Distress Syndrome (ARDS): symptoms, pathogenesis
• Diffuse damage to alveolar wall
Symptoms
o Sudden onset of severe dyspnea, tachypnea
Pathogenesis
o Activation of pulmonary macrophages ->
o Cytokine Release
->
o Stimulation of neutrophils – release enzymes + free radicals ->
o Damage to endothelium and alveolar epithelium ->
o Severe Edema
Atelectasis
• Collapse or incomplete expansion of alveoli
Congenital:
• Failure of lungs to expand at birth
Acquired
• Restrictive - pressure on lungs - > fibrosis
• Obstructive - collapse distal to obstruction due to resorbed fluid
Emphysema
- Emphysema- air trapped in alveoli or interstitium
- Reduced ventilation -> ventilation/perfusion mismatch
- Expiratory dyspnea
- Hypoxia and hypercapnia
Pulmonary Hypertension
• Increased pulmonary vascular resistance
Causes
• Vasoconstriction
• Vascular obstruction
• Vascular volume overload
Usually secondary to other dz
• Cardiac dz, lung dz, thromboembolism, hypervolemia
Cellular Changes in Pneumonia
Fibrin
o Sign of acute severe injury
Neutrophils
o Predominate with most bacterial infections
Macrophages
o Alveolar macrophages come quickly
o More macrophages with chronicity
Alveolar septal response to Pneumonia
Acute
o Edema and leukocytes in the interstitium
Chronic
o Squamousmetaplasia
o Fibrosis
o Non-suppurative inflammation
Transient Vs Chronic Injury in pneumonia
Transient Injury
• Complete repair in <1wk
Chronic Injury
• Fibrosis (restricts alveoli)
Classification of pneumonia
Etiology
o bacterial, viral, parasitic, toxic
Type of inflammation
o Suppurative
o Fibrinous
o granulomatous
Distribution o Cranioventral - o Lobar o Diffuse o multifocal
Morphologic type
o Broncho
o Interstitial
o bronchointerstitial
Distribution of Pneumonia
- Multifocal - granulomatous
- Lobular (ruminants)
- Lobar – usually cranioventral
- Dorsocaudal - parasitic
- Diffuse
Bronchopneumonia; facts, Resp signs, Systemic signs
- Most common pneumonia
- Origination of inflamm @ bronchiolar-alveolar junction
- Aerongenous
- Bacterial
- Cranioventral
Respiratory Signs o Productive cough o Tachypnea o Dyspnea o Wheeze o Exercise intolerance
Systemic Signs o Lethargy o Anorexia o Fever o Weight loss o Rough coat
Suppurative Bronchopenumonia
o Obstructive due to exudates
o Often bilateral, cranioventral (lobar), or lobular
o Acutely lungs are swollen and consolidated
o Over time exudates resolve, lung often atelectatic
Fibrinosuppurative Bronchopneumonia; basics, histo
o more severe than suppurative o lobar pattern o Protypical example: Shipping fever o Can be caused by aspiration o Hemorrhage, fibrin, necrosis o Complete resolution is uncommon
Histo
• Acute - massive fibrin + neutrophils in airspaces
• Chronic- Fibrosis of severely damaged tissues = permanent changes
Interstitial Pneumonia; histo, entry & two types of damage
Histo
• diffuse to patchy damage to alveolar septa
• Type II pneumocyte hyperplasia
Entry
o Aerogenous – inhalation of toxic gases
o Hematogenous – spread via the blood (most common)
Primary epithelial damage
o Toxic gasses, local generation of toxic compounds by metabolism in clara cells
o Damage secondary to viral infections
Primary endothelial damage
o Septicemia, DIC, migrating parasite larvae, endotheliotropic viruses, immune complex disease
Acute Bovine Pulmonary Edema & Emphysema (fog fever); pathogenesis, symptoms, histo
o Example of interstitial pneumonia
Pathogenesis
• Cow used to poor forage moved to lush pasture (high in L-tryptophan) ->
• L-tryptophan converted to 3-methylindole in rumen ->
• 3-MI absorbed into circulation ->
• Metabolized to toxic intermediate by Clara cells (toxic to pneumocytes and endothelium) ->
• Necrosis ->
• Acute edema and interstitial emphysema
Symptoms
• Severe dyspnea, froth from mouth, mouth breathing, extended neck
• NO FEVER
Histo
• Edema, emphysema, Type II pneumocyte hyperplasia
Chronic Interstitial Pneumonia; histo, gross lesions, causes
Histo Lesions
• alveolar fibrosis
• Macrophages, lymphocytes, plasma cells in interstitium
Gross Lesions
o Lungs don’t collapse
o rib impressions on surface of lungs
Causes
o Viral (mostly)
o Mycoplasma
Embolic Pneumonia
- Septic emboli lodge in lungs
- Bacteria trapped in vessels -> infections spreads into interstitium
- random multifocal distribution
Granulomatous Pneumonia; causes
- Well circumscribed, variably sized, firm nodules
- May be mineralized
- Random distribution
- Usually chronic
- aerogenous or hematogenous
Causes
o Fungi, bacteria, foreign material, migrating parasites
Neoplasia of the lungs
- Primary = uncommon
- Metastatic from other place common
- Ex: Feline lung-digit syndrome
Feline Lung Digit Syndrome
- primary pulmonary tumor (carcinoma or adenocarcinoma)
- commonly metastasize to digits
- mass on digits in cats indicative of pulmonary neoplasia
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Reserve Capacity of the kidney
- Can lose 66% of nephrons and have normal function
- loss of ~70% of nephrons = Isosthenuria
- loss of 70-75% of nephrons = Azotemia
- Further nephron loss = Renal Failure and Uremia
Function of the glomerulus
- Filtration barrier between blood and urinary space
* Restricts cells & proteins
Function of Proximal convoluted tubules
- Protein resorption (few that made it thru glomerulus)
- Resorption of 65% H2O, amino acids, glucose, Na, K, Cl
- High metabolism = sensitive to hypoxia & toxins
Function of Loop of Henle
- Resorption of 20% H2O, Na, Cl
* Maintains concentration gradient in medulla
Function of Distal Convoluted Tubule
- Resorption of water due to ADH
- Resorption of Na and excretion of K due to ALD
- Save the Na pee the potassium
Function of Collecting Duct
Resorption of H2O due to ADH
Blood Flow in the nephron
o nephrons required to maintain conc. gradient of interstitium
o conc. gradient in interstitium required for functional nephron
4 Nephron Endocrine Functions
Produces renin (RAS) o increases blood vol
Erythropoietin production
o In response to hypoxia
o Stimulates RBC production
Activates Vit D
o Helps Ca absorbtion
Degradation of PTH
o Ca homeostasis
How does renin increase blood volume?
o Decreased renal profusion (dehydration, hemorrhage, heart failure, etc) ->
o production of renin ->
o converts angiotensinogen into angiotensin I ->
o Ang I into Ang II by ACE produced by lungs ->
o Ang II vasoconstricts arterioles AND
o Ang II goes to pituitary to stimulate ADH production ->
o ADH causes resorption of water in distal tubules AND
o Ang II works on adrenal gland to produce ALD AND
o Ang II constricts efferent arterioles to insure time to filter blood
Azotemia
o Elevated BUN/creatinine
o Consequence of reduced GFR
Pre-renal
• Decreased renal profusion
• Azotemia but maintaining conc ability
Renal
• When >75% of nephrons are non-functional
• Azotemia w/ loss of ability to concentrate urine (isosthenuria)
Post Renal
• Obstruction of outflow of urine
Uremia
o Clinical syndrome due to renal failure
o Functional reserve of kidney lost
o Acute kidney injury or chronic renal failure
o Many multisystemic symptoms
Signs of Kidney Disfunction
- Azotemia
- Uremia
- change in urine quantity
- change in urine conc.
- Proteinuria
- Hematuria
- Glucosuria
- Urinary Casts
- Changes in production of erythropoietin, calcitrol, renin
Requirements to conc urine & chsnges in urine due to kidney dysfunction
Requirements to conc urine
• Functional interstitium
• ADH responsive epithelial cells in distal nephron
• ADH
o Polyuria
Isosthenuria: osmolarity of urine = plasma
• w/ Azotemia: likely renal failure
• No azotemia: may be appropriate or renal dz because conc. ability lost before azotemia shows
Proteinuria
Pre-renal
• Hemoglobinuria, myoglobinuria, bilirubinuria, ketonuria
Renal • Glomerular • increased permeability (very high) • Tubular • inability to resorb proteins (typically low)
Post Renal
• Most common
• Lower urogenital tract dz
Calcitrol & Renal Failure
o active Vit D3
o Produced via 1α-hydroxylase in renal tubular cells
o Promotes absorption of Ca from gut
o Chronic renal failure (CRF) can be associated with hypocalcemia
Erythropoietin & Renal Failure
o Produced by kidney in response to hypoxia
o Stimulates RBC production
o Chronic renal failure (CRF) can be associated with non-regenerative anemia
Renin & Renal Failure
o Chronic renal failure (CRF) -> increased renin ->
o Increased blood vol. ->
o Hypertension
Renal Dz Vs Renal Failure Vs End Stage Kidney
Renal Dz
o Lesions in kidney
Renal Failure
o Clinical syndrome due to decreased renal function
End stage
o Chronic, irreversible, progressive dz that results in common pathologic state
o Comparable to cirrhosis of liver
Kidney Response to Injury
o New nephrons not formed following renal maturation
o Nephron function is all or nothing
o Damage to one component = decreased function of other components
Glomerular Response to Injury
Acute
• Proliferation or necrosis of cells
• Rupture or thickening of basement membrane
• Infiltration of inflammatory cells
Chronic
• Atrophy and fibrosis of glomerular tuft
Tubule Response to Injury
- Epithelial cells: Degeneration, necrosis, atrophy
* Epithlium can regenerate if basement membrane is intact!
Interstitial Response to Injury
Acute:
• edema,
• hemorrhage,
• inflammation
Chronic:
• inflammation,
• fibrosis
Pre-renal disorders (Circulatory); USG, causes
Underperfusion
• Decreased GFR = azotemia w/ concentrated urine
• Activation of RAS
• If severe and prolonged -> Ischemic necrosis
Hyperemia / Congestion
• Acute septicemia
Hemorrhage
• Renal cortical or large
Infarction
• Vascular occlusion (wedge)
• Necrosis + hemorrhage -> fibrosis
Cortical necrosis
• DIC secondary to septicemia, endotoxemia
Medullary necrosis
• due to NSAIDs
How do NSAIDs cause medullary necrosis
- NSAIDs ->
- decreased prostaglandins ->
- vasoconstriction ->
- local ischemia ->
- necrosis
Pre-renal disorders (ADH disturbance)
o Diabetes insipidus
Neurogenic
• Pituitary gland does not produce ADH
• No ADH -> decreased urine concentration -> PU/PD
• Kidneys are normal
Nephrogenic
• ADH produced normally
• Kidney’s can’t respond -> decreased urine concentration
Pre-renal disorders (ALD disturbance)
Deficiency
• Adrenocortical insufficiency
• Excessive loss of Na & retention of K
• Elevated K -> bradycardia
Excess
• Excessive RAS activation
• congestive heart failure
4 Signs of Glomerular Dz
o Proteinuria
• Most important loss of Albumin
• Protein loss > resporptive capacity of PCT -> Proteinuria
• No azotemia & No change in GFR
o Hypoalbumenia
o Edema
• Decreased oncotic P -> activation of RAS -> fluid retention
o Hyperlipidemia
• Hypoalbuminemia -> increased synthesis of lipoproteins
Glomerular Nephritis basic & early stages Vs progressive
o “Inflammation” of the glomerular tuft
o common cause of renal failure in dogs
o usually cannot identify Ag involved
Early stages
• Urine concentrating ability is still intact
Progressive
• Loss of entire nephron -> renal failure/uremia/etc
Classification of Glomerular Nephritis
Membranous
• thickening of capillary basement membranes
Proliferative
• increased cellularity of glomerular tuft
Membranoproliferative
• Both
Pathogenesis of Glomerular Nephritis
- Endogenous or exogenous Ag Binds Ab ->
- Ag/ab complex circulates and lodges in glomerular capillaries ->
- Fix complement -> inflammation + bioactive mediators
Gross & Histological Lesions of Glomerular Nephritis
Gross Lesions • Often none! • Glomeruli may be prominent (red dots) • Chronic • Renal fibrosis = shrunken, granular, pale grey dots
Histo Lesions • Cellular proliferation • Thickening of the basement membrane • Abnormally porous • Glomerulosclerosis
Amyloidosis
o Less common than glomerular nephritis
o Amyloid may be deposited in other sites
o Mostly dogs, sometimes cows
o Present w/ CRF
o Always chronic, progressive and irreversible
o Breed dispositions: shar pei, Asian cats
Amyloidosis: Gross & Histological Lesions
Gross Lesions • Acute: o none • Chronic: o capsular surface irregular & mottled o iodine makes glomeruli black & prominent
Histology
• Amorphous eosinophilic material w/in glomeruli
• Congo red stain = apple green
• Advanced cases: extensive fibrosis
• Surviving tubules contain abundant protein casts
Amyloid; where is it deposited, 2 forms
- Insoluble fibrillary protein that is resistant to proteolysis
- Deposited in mesangium between endothelium and basement membrane
Forms:
• Reactive
• Idiopathic
Renal Tubule dysfunction; symptoms, causes
o Impaired urine concentrating ability -> Isosthenuria, PU/PD
Pre-renal
• Diabetes Insipidus
• Adrenocortical
Renal
• Loss of sufficient nephrons
Uremia & causes
- clinical syndrome associated with fluid, electrolyte, hormone imbalances, and metabolic abnormalities due to renal failure
- FATAL if not corrected
Causes
• Electrolyte/fluid imbalance
• Uremic toxins
Uremia Pathophysiologies
- Dehydration
- Edema
- Metabolic acidosis
- Non-regenerative anemia
- Vomiting
- Ulcerative/necrotic stomatitis
- Malaise, lethargy
- Weight loss
- Electrolyte Issues
Changes in K, P, Ca due to Uremia in dogs, cats, cows, horses
Potassium and blood pH
• Dogs, cats, horses:
• Hyperkalemia and acidosis: oliguric or anuric (AKI)
• Hypokalemic: polyuric (CRF)
• Cattle:
• Hypokalemic: alkalosis, decreased intake, increased salivary excretion
• Alkalosis + hypochloremia: Sequestration in atonic abomasum
Phosphorous • Dogs, cats, horses: • Hyperphosphatemia • Decreased renal clearance • Cattle: • +/- hyperphosphatemia • Salivary secretion
Calcium • difficult to predict! • Dogs, cats, cattle: • Usually low normal to mild hypocalcemia in CRF • Secondary hyperparathyroidism • Horses: • Often hypercalcemic • Normally have high renal excretion
Gross Lesions of Uremia
o Ulcerative and hemorrhagic gastritis
o Gastric mucosal mineralization
o Subpleural intercostal mineralization
o Chronic renal lesions + Renal mineralization
Renal Secondary Hyperparathyroidism; basics & pathogenesis
o Sequel to chronic renal failure
Pathogenesis • CRF -> • Increased phos retention + decreased Ca absorption -> • Hyperphosphatemia and hypocalcemia -> • PTH secretion -> • Ca resorption from bone
Renal Secondary Hyperparathyroidism; lesions
Renal fibrous osteodystrophy
• Increased PTH -> demineralization of bone -> replacement with fibrous connective tissue
• Dogs: Rubber jaw
Soft tissue mineralization
• Dystrophic & metastatic
• Common in stomach, lungs, pleura, kidneys
Acute Kidney Disease; presentation & general causes
Presentation
• Sudden loss in nephron function
• Failure of excretory, hemodynamic and filtration functions
• Potentially reversible if diagnosed and treated early
Causes o Inadequate renal perfusion o Urinary obstruction o Massive renal infection o Massive/multiple renal infarctions o Acute tubular necrosis
Acute Tubular necrosis; basics & pathogenesis
- Most common cause of Acute kidney injury
- Ischemic or toxic damage
- NOT inflammatory
Pathogenesis
• Sudden death of tubular epithelial cells ->
• Shedding casts into tubular lumen ->
• dead cells cause Intratubular obstruction ->
• filtrate leaks back into kidney ->
• Damage to tubules causes increase in Renin ->
• Excessive vasoconstriction & GFR
Causes of Acute Tubular necrosis in horses, cattle, dogs, cats, all species
Horses
o Aminoglycoside antibiotics
o Rhabdomyolysis
o NSAIDs
Cattle o Heavy metals o Plants Oak leaf poisoning o Hemo/myoglobinuria o Leptospirosis
Dogs o Grapes, o NSAIDs, o aminoglycosides, o chemo therapteutics, o antifungals o Leptospirosis
Cats
o Lilies
o NSAIDs
All Species!
o Ethylene glycol!!
Acute Tubular necrosis gross lesions & histo
Gross Lesions
• minimal renal swelling
Histology
• PCT most susceptible to ischemic and toxic insults
• Tubular epithelial degeneration and necrosis
• Sloughing of cellular tubular into lumina
• Interstitial edema
Chronic Renal Failure basics & first function lost
- An irreversible and progressive disease
- First function lost is concentration ability -> PU/PD
- Poor long term prognosis, but many patients with CRF often survive months to years
- Can progress to end stage kidney
Chronic Renal Failure: Gross & Histo Lesions
Gross:
o Shrunken, firm, vaguely nodular kidney
o Loss of parenchyma + replacement by fibrosis
Histo:
o Interstitial fibrosis
o Sclerotic glomeruli
o Mononuclear tubulointerstitial inflammation
o Thin, dilated tubules with attenuated epithelium
Causes of Chronic Renal Failure
- Inciting cause is not evident
- Any portion of nephron targeted
- Congenital
- Chronic pyelonephritis
- Ischemia
- Glomerularnephitis
- Amyloidosis
- Acute kidney injury w/ a lot of damage
Acute Kidney Injury Vs Chronic Renal Failure: frequency of urination, clinical symptoms, lab findings, imaging findings
Frequency of Urination
o AKI: Oliguric/Anuric
o CRF: Polyuric
Clinical findings
o AKI: symptoms of underlying cause
o CRF: Thin, rough hair coat, pale
Lab findings
o AKI: Hyperkalemia, hyperphosphatemia
o CRF: Hypokalemia, hyperphosphatemia, anemia, hyperparathyroidism
Gross/imaging findings
o AKI: kidneys normal to enlarged
o CRF: kidneys small
Interstitial Nephritis: basics & 2 forms
- inflammation in the interstitium
- Often mild and incidental
- Usually associated with some degree of fibrosis (if chronic)
Suppurative
• usually bacterial and hematogenously spread
Nonsuppurative:
• lymphoplasmacytic or granulomatous
Causes of Suppurative Interstitial Nephritis
o Leptospirosis o White spotted kidney o MCF o FIP o Infectious canine hepatitis o Systemic granulomatous disease
Pyelonephritis: basics and what does a UA look like
- Inflammation centered on renal pelvis
- Ascending infection
- Often Bilateral & Females
- Animals usually sick/painful
- progress to renal failure
UA:
• casts, hematuria, proteinuria, bacteruria,
pyuria
Progressive Renal Nephropathies in dogs
- Dysplasias of several breeds
- unknown inheritance pattern
- Persistent PU/PD, progressing to CRF
- Severe bilateral renal fibrosis in young dogs
Interstitial Amyloidosis
- amyloid in interstitium of lungs
- Cats w/ CRF
- Cause unknown
- +/- glomerular amyloidosis
- takes up congo red stain
Granulomatous Nephritis
- Systemic granulomatous disease
* Classic example: FIP
Papillary Necrosis
• Caused by NSAIDs
Renal Neoplasias
o Primary renal neoplasia
• uncommon
Epithelial:
• Renal adenoma/adenocarcinoma or transitional cell carcinoma
Mesenchymal:
• Rare
o Multicentric
• Lymphoma (cats, cattle, chicken)
o Metastatic
• More common
o Embryonic
• Nephroblastoma (pigs & dogs)
Developmental Anomalies of kidneys
o Aplasia, hypoplasia, dysplasia
o Ectopic kidneys
o Fused kidneys
o Polycystic kidneys (cats)
Renal Parasites
Dogs
• Dioctophyma Renale
Pigs
• Stephanurus dentatus
Signs of Post renal dysfunction
o Incontinence o Anuria o Pollakiuria o Dysuria o Stranguria o UTI
UTI
- Inflammatory
- Common in Dogs & cats
- Can be subclinical
- Can extend to genital structures.
- Can result in septicemia
- Bacteria: fecal in origin
- Horses: Foaling injury or urogenital conformation
Cystitis; two causes
Caused by toxin (few)
Caused by bacteria (most)
Chronic cystitis
- Mucosal hyperplasia
- Nodular lymphoplasmacytic infiltrate
- Chronic inflammation or irritation
- Mycotic cystitis may occur
Urolithiasis; basics & risk factors
- Oversaturation of urine substances -> precipitation and growth
- May lodge in urinary tract -> Life threatening!
- Common sites of obstruction dependent on species
- Males predisposed
Risk Factors • UTI • urine stasis • urine pH • hereditary
Feline Urologic Syndrome (FUS) or Lower Urinary Tract Disease (FLUTD): clinical signs & presentation
• Multifactorial disease
Clinical signs
• Dysuria, hematuria, crystalluria, inappropriate urination, urethral obstruction
Clinical presentation
• Obstructed
• Unobstructed- recurrence possible
Ruptured Bladder
- Foals (during birth), Steer, goats
* Measure abdominal Cr/K vs serum Cr/K
Neoplasia of Lower Urinary Tract: basic & symptoms
- Transitional Cell Carcinoma
- Most common near trigone
- In cattle, may be associated with Braken Fern
Symptoms
• Dysuria, hematuria, obstruction
3 Developmental Abnormalities of lower urinary tract
Patent urachus
Persistent urachal remnant
• May predispose to cystitis
Ectopic ureters
• Ureters open directly into the urethra
• incontinence
Bacterial cystitis: risk factors, symptoms, lesions
- Lower urinary tract = sterile
- Ascending infection
Risk Factors o Retention of urine o Trauma o Glucosuria -> Emphysematous cystitis o Obstruction
Symptoms
o Dysuria & pollakiuria
o Urine: Cloudy, odiferous, red-tinged
o Pyuria, hematuria, bacteruria
Lesions
o Thickened bladder wall w/ Edema & inflammatory infiltrates
Define: systole, diastole, pre-load, after load
Systole:
o ventricular contraction
o “pumping”
Diastole
o the period of ventricular relaxation
o “filling”
Preload
o The quantity of blood returning to the heart during diastole
o Diastolic wall stress
o Related to venous pressure
Afterload
o Impedance to ventricular emptying
o Systolic wall stress
o Related to systemic blood pressure
Define: cardiac output & stroke volume
Cardiac Output
o Stroke volume x heart rate OR
o Blood pressure / systemic Vascular Resistance
Stroke Volume
o Increases when myocardial contractility & preload are increased
o Decreases when afterload is increased
Renin-angiotensin system
o Activated in response to low Cardiac output
o Goal: Increasing blood volume
by maintaining systemic blood pressure
o Renal failure -> systemic hypertension & hypervolemia
Forward Vs Backward Heart Failure
Forward:
o Poor Cardiac output
Backward:
o Back up into venous circulation (Congestive heart failure
Acute L Ventricular Failure; forward, backward, causes
Forward Failure
o Decreased CO -> Decreased Systemic BP -> Increased Sympathetic Tone ->
o Shunting of blood from skin, GI tract, and kidneys to brain and heart
o Pale mucous membranes
o Oliguria
Backward Failure
o Decreased CO -> Backup into left atrium -> lungs ->
Pulmonary congestion and edema
Causes o Large ventricular septal defects o Infarction of left ventricle o Bacterial endocarditis o Acute myocarditis o Conduction failure
Acute R Ventricular Failure; forward, backward, causes
Forward Failure
o Decreased CO -> Decreased pulmonary BP -> Increased Sympathetic Tone ->
o Shunting of blood from skin, GI tract, and kidneys to brain and heart
o Pale mucous membranes
o Oliguria
Backward Failure
o Decreased CO -> Backup into R atrium -> systemic ->
o Systemic congestion of liver
Causes
o Pulmonary thromboemboli
o Acute myocarditis
o Infarction of right ventricle
Acute biventricular failure
• Right ventricle is a weaker muscle -> signs primarily of right heart failure first
Causes
o Acute, severe, bilateral myocarditis
o Cardiac tamponade
3 forms of Chronic Heart Failure
• Failure of Adaptive mechanisms -> Decompensated -> decreased Cardiac output
Left sided CHF
o Back up/congestion in lungs
Right sided CHF
o Back up/congestion in systemic circulation (liver)
Physical signs of congestive heart failure L Vs R
Left (Respiratory symptoms) o Rales (alveolar edema) o Frothy, pink expectorant o Shortness of breath, tachypnea o Dyspnea o Cough
Right (systemic venous congestion) o Generalized venous engorgement (jugular pulse) o Hepatomegaly o Ascites o Pleural effusion (cats L & R) o Pericardial effusion (cats L & R) o Dependent peripheral edema o Weight gain (retained fluid)
3 Heart Adaptations to injury
Cardiac Dilation
o Frank-Starling Phenomenon
• as a myocyte stretches, the contractile force is increased
o W/ excessive stretch, contractile strength is decreased
o Seen in decompensated heart failure
o Triggers hypertrophy
Cardiac Hypertrophy
o To relieve stress on wall, cells grow large = “stronger”
o Pressure overload = concentric hypertrophy
o Volume overload = eccentric hypertrophy
Activation of Neuro-hormonal Mechanisms
Activation of Neuro-hormonal Mechanisms in response to heart injury
o Increased HR, stronger contractions, vasoconstriction
AND
o Decreased cardiac output ->
o Activation of renin-angiotensin system ->
o Vasoconstriction
o Increased ADH -> water retention
o Increased aldosterone -> Na & water retension
o All can lead to cardiac edema
2 Mechanisms behind Cardiac Edema
Backwards failure
• increased systemic/pulmonary venous pressure ->
• hemodynamic edema
Forward failure
• activation of RAS -> water retention -> hypervolemia -> edema
Treatment of Cardiac Failure
o Goals = Improve CO
Forward failure
• Increase stroke vol -> Increase CO
• Decrease afterload -> increase CO
• Arteriodilators, diuretics, ACE inhibitors, beta blockers
Backward Failure
• Decrease/normalize preload -> decrease congestion
• Venodilators, diuretics, ACE inhibitors, cardiac conduction modulators
Cor Pulmonale
o Heart dz secondary to lung or pulmonary vessel dz
Acute
• Usually secondary to thrombus/embolus in pulmonary artery or its large branches
Chronic
• Usually secondary to chronic hypoxia and/or pulmonary hypertension
• Ex: brisket & heartworm Dz
Chronic Cor Pulmonale: Brisket Dz
- Cattle pastured >6000 ft
- Low O2 -> chronic hypoxia ->
- Chronic pulmonary hypertension ->
- R ventricular backwards failure -> peripheral edema
Chronic Cor Pulmonale: Heartworm Dz
• Adult Dirofilaria immitis live in pulmonary arteries ->
• pulmonary hypertension
&
• Worms cause damage to vessels -> pulmonary hypertension
&
• Migration of worms can predispose to pneumonia -> chronic hypoxia -> pulmonary hypertension
Basics of Aortic Valve Dz
o Stenotic, regurgitant, or both
Aortic stenosis
• stenosis of valve = smaller opening -> increase L ventricular P -> concentric L ventricular hypertrophy
Aortic Insufficiency
• Leaky valve -> blood leaks back into LV -> heart must increase Vol of blood pumped -> L ventricular dilation & eccentric hypertrophy
Endocardiosis: basics, groos, & histo
- Chronic degenerative valvular dz
- Older animals, Dogs, (small breeds)
- Murmur
- Does NOT always cause Cardiac Failure
- Left A-V (mitral) most common
Gross
• Thick, smooth, white, opaque nodules
Histo
• Myxomatous degeneration
Pathophysiology of endocardiosis
- Abnormal valve ->
- Regurgitation ->
- left atrial dilation + left ventricular dilation ->
- eccentric hypertrophy ->
- decrease COutput ->
- increased Renin ->
- increased blood volume ->
- increased preload
Valvular endocarditis: basics & gross/histo lesions
- Infection/ inflammation of endocardium lining the valves
- No age or species predilection
- Dogs: Mitral is most common
- Ruminants: Tricuspid most common
- Murmurs are common
- Does NOT always cause cardiac failure
- Undulant fever
Gross
• Rough, yellow, grey, red, friable
Histo
• Fibrin, bacteria, leukocytes
Pathophysiology of Valvular endocarditis
- Bacteremia + endothelial injury/turbulence/hypercoagulability ->
- Bacterial adherence to valve ->
- Proliferative/inflammatory lesion ->
- Septicemia, thromboembolism, glomerulonephritis, valvular fibrosis, myocardial abscessation
Dilated Cardiomyopathy
- Congestive heart failure is often the first sign
- All 4 chambers are enlarged, Thin, flabby
- Dobermans and Boxers
- Probably genetic
Hypertrophic Cardiomyopathy & what are the results
- Most common in cats
- Ventricular Hypertrophy without dilation
- Genetic in Maine Coon
Results
o Decreased ventricular vol & resistance to filling = reduced preload
o Obstruction to outflow = increased afterload
o Myocardial necrosis = decreased contractility
o Atrial thrombosis = reduced preload
Restrictive Cardiomyopathy
- Less common
- Mostly in cats
- Decreased diastolic vol due to fibrosis
Secondary Cardiomyopathy causes in cats; Nutritional causes in other animals, gross/histo lesions
- Systemic dz
- Can be from hyperthyroidism in cats, toxins, or injury
Mostly nutritional cause
• Vit E/selenium deficiency -> dz in cows & pigs
• Taurine deficiency -> dilated cardiomyopathy in cats
• Grain free -> dilated cardiomyopathy in dogs
Gross
• Pale streaks, fibrosis/minerlization
Histo
• Cellular degeneration/necrosis, Fatty change, Fibrosis, mineralization
Hydropericardium
• Clear to straw colored, watery, fluid
Causes • Any causes of generalized edema • Toxemias • Anemia (esp in pig) • Neoplasms • Idiopathic
Hemopericardium
• Blood
Causes • Rupture of hemangiosarcoma • Rupture aorta • Ruptured myocardium • Iatrogenic
Pericarditis basics, gross, & route
- Inflammation w/in pericardium
- serous, fibrinous, purulent exudate
Route • Hematogenous • Extension from myocarditis • Extension from lymphatics • Traumatic penetration
Traumatic Pericarditis
• Reticulopericarditis = “Hardware Disease”
Pathophysiology
• Cattle swallows wire/nail/sharp object ->
• normal ruminal/reticular contractions ->
• penetration of object through diaphragm & pericardium ->
• direct implantation of bacteria
Can cause
o Fibrinopurulent pericarditis
o Restrictive/constrictive pericarditis
o Congestive heart failure
Cardiac Compression; acute & chronic causes & result
• Rise in intrapericardial pressure -> compression of great veins, atria, & ventricles (R side first)
Acute Causes
• cardiac tamponade
• Hemorrhage
• Acute heart failure
Chronic
Causes
• Effusions, constrictive pericarditis, tumors
Result
• congestive heart failure (right sided)
Congenital Cardiac Dz: signalment & concequences
Young animals w/ • Cardiac murmur • Polycythemia • Cyanosis • Congestive heart failure
Consequence
• Shunting of blood
• Obstruction of blood flow
Treatment of Cardiac Failure: increase SV, Decrease Afterload, decrease Preload
Increase SV
• (+) ionotropes
• cardiac conduction modulators
Decrease Afterload • arteriodilators • ACE inhibitors • beta blockers • diuretics
Decrease Preload
• venodilators
• ACE inhibitors
• diuretics
4 Congenital Cardiac Defects
Congenital shunts
• L to R or R to L
Pulmonic Stenosis
• Constriction of pulmonary artery or valve
Aortic Stenosis
• Constriction of endocardium just below aorta
Persistent R Aortic Arch
• Ligamentum arteriosum forms a band over the esophagus -> megaesophagus
L to R Congenital Shunt
o Oxygenated blood from L side goes through the lungs a second time
o No cyanosis
o Due to ventricular septal defect OR
Patent ductus arteriosus (PDA)
• Small patency
• SVR > pulmonary vascular resistance
R to L Congenital Shunt
o Poorly oxygenated blood from the R heart bypasses the lungs
o CYANOSIS
Tetralogy of fallot • Ventricular Septal Defect • Subpulmonic Stenosis • Overriding (Dextraposed) Aorta • Right Ventricular Hypertrophy
Patent ductus arteriosus (PDA)
• Large & chronic
• Pulmonary arterial hypertension->
• increased pulmonary vascular resistance > systemic vascular resistance -> right ventricular hypertrophy -> right to left shunt
Endocardiosis V Endocarditis
Endocardiosis • Dogs • Older • Afrebrile • Murmur • Smooth, white, nodular expansions of the valve • Myxomatous degeneration
Endocarditis • Any species • All ages • Undulant fever • Murmur • Rough, friable, tan/grey/red aggregates on the valve • Inflammation, fibrin, necrosis
Arteriosclerosis
- not common in vet med
* affects primates & birds due to old age & inappropriate diet
Arteritis
- Feature of many infectious and immune-mediated diseases
- Viral, Bacterial, Mycotic, Parasitic, Immune mediated
- Ex: Verminous Arteritis
Verminous Arteritis
• Horses
Pathophysiology
o Larvae migrate through colonic wall into mesenteric arterioles to root of the cranial mesenteric artery
->
o Damage to arteries ->
o inflammation (arteritis), dilation (aneurysm), thrombosis ->
o downstream ischemia/infarcts in gut
Arterial Rupture
• Due to trauma, abnormality, or spontaneous
Horses
o Aortic rupture
o Carotid artery rupture secondary to guttural pouch infection
Turkeys
o Aortic rupture
Arterial Occlusion
Thrombosis
o damage to vessel wall -> local clotting
Thromboembolism
o formation of thrombus -> embolizes -> flows downstream -> obstruction
Aneurysms
- dilation due to abnormal blood flow
- Usually arterial
- Caused by congenital anomaly, trauma, arteritis, etc
Venous Dz
- Portocaval shunts
- Phlebitis (inflammation)
- Venous thrombosis
Primary Cardiac Tumors
Hemangiomas
• Benign neoplasms of the skin of dogs
Hemangiosarcomas
• Spleen and right atrium in dogs
• Highly metastatic!
Hemangiopericytomas
Rhabdomyomas and rhabdomyosarcomas
• Rare
Metastatic & Heart Base Tumors
Metastatic
• Lymphoma
Heart Base
• Aortic body tumors
• Ectopic thyroid/parathyroid
Words for White & Grey Matter of Brain
o Leuko – white
o Polio - grey
Lesion Localization Supratentorial V Infratentorial
Supratentorial
• Focal lesion will affect contralateral side
• Signs of dysfunction: Behavior, Initiation of Movement, Seizures
Infratentorial
• Brainstem & cerebellum
• Focal lesion will affect ipsilateral side
• Signs of Dysfunction: Wakefulness, Breathing, Vestibular System
Upper Motor Neuron Dz Vs Lower Motor Neuron Dz
Upper Motor Neuron Dz
• Paresis (weakness)
• Hyperreflexia/clonus = lack of inhibition of myotactic reflexes
• Spasticity/hypertonia = lack of inhibition of lower motor neurons
Lower Motor Neuron Dz • Hypotonia/flaccidity • Hyporeflexia/areflexia • Paresis/paralysis • Muscle atrophy
Lesion Localization in Spinal Cord
C1-C4 (cervical)
• UMN signs to all 4 limbs
C5-T2 (cervicothoracic)
• LMN to front limbs
• UMN to hind limbs
T3-L3 (Thoracolumbar)
• UMN signs in hindlimbs
L4-S2 (lumbosacral)
• LMN signs to hindlimbs, perineum, pelvic viscera
S3-C
• Controls tail
CNS Response to Injury
- Limited regeneration
- Damage to cell body = loss of nerve & axon
- Damage to axon = necrosis of axon distal to injury (Wallerian degeneration)
Wallerian Degeneration on Histo
- Swollen hypereosinophilic axons = spheroids
- Swollen myelin sheaths = vacuoles in white matter
- Microglia phagocytose degenerate axon = Gitter Cell
- Gitter cell + swollen myelin sheath= digestion chamber
Space Occupying Lesions in CNS
- CNS encased in bone
- Little swelling = compression
- “Benign” hemorrhage or edema = profound CNS signs/damage
CNS & Susceptibility to Injury
- pathogens that would not necessarily cause disease in other tissues cause severe CNS disease
- Neurons > oligodendroglia > astrocytes > microglia > endothelium
Neurons
• most susceptible
• Minimal energy Stores
• High oxygen needs
Portals of Injury for Infectious Dz of the brain
- Direct extension (stab, ear)
- Hematogenous
- Leukocyte migration
- Retrograde axonal migration
Abscesses in Brain; histo & clinical signs
• Uncommon
Histo:
• Neutrophils and macrophages, necrosis, gliosis at periphery
Clinical signs:
• Dependent on location
• Tissue damage + space occupying lesion
Suppurative meningitis/meningioencephalitis; who does it affect, portal, common bacteria, clinical signs, gross & histo lesions
• Common in young food animals
Portal
• Usually septicemia
Common organisms:
• E coli, Salmonella sp, Streptococcus sp
Clinical signs • Usually ill- fever, anorexia • Depression • Cranial nerve deficits • Seizures/coma
Gross:
• Pale yellow, cloudy meninges
• +/- hemorrhage
Histo:
• Neutrophils +/- bacteria
Listeria Monocytogenes; basics & associated syndromes
- Gram (+) bacteria
- ruminants
- source is poorly cured silage
Syndromes
• Abortion
• Encephalitis
• Septicemia
Listeria Monocytogenes; portal, histo, clinical signs
Portal:
• Invasion of sensory and motor nerves in oral cavity ->
• Retrograde + anterograde extension up trigeminal nerve (CN5) ->
• trigeminal ganglion ->
• brainstem (pons)
Histo
• Suppurative inflammation (microabscesses)
Clinical Signs • Dullness • Circling • CN deficits • Fever
Thrombotic Meningoencephalitis; who does it affect, organism involved, portal, gross & histo, clinical signs
• usually feedlot cattle
Organism
• Histophilus somni, gram (–) bacteria
Portal
• Hematogenous
Gross
• Random multifocal hemorrhage
Histo
• Vasculitis with thrombosis
• Secondary suppurative inflammation, necrosis
Clinical Signs
• Fever, anorexia, depression
• Variable neurologic signs
• Ataxia, circling, head pressing, blindness, death
Distemper Virus (morbilivirus); Basics, Initial signs, Pathogen/phys,
- Vaccines = severely reduced incidence
- Wildlife reservoirs
Initial signs:
• conjuncitivis, rhinitis, diarrhea
Pathogen/phys • Aerosolization between animal -> • local, then systemic lymph -> • leukocytes -> • brain -> • Oligodendrocytes -> • demyelination -> • encephalomyelitis
Distemper Virus (morbilivirus); Histo & Associated Lesions
Histo • Random multifocal • Nonsuppurative perivascular cuffs • Vacuolation of the white matter • Cytoplasmic and intranuclear inclusions
Associated Lesions
• Hard foot pads
• Enamel hypoplasia
Distemper Virus (morbilivirus); 2 Clinical Syndromes
• 50-70% subclinical
“Classic” encephalitis (acute)
• Unvaccinated puppies
• Early - Fever, conjunctivitis, respiratory signs, V/D, death
• Neurologic signs - seizures, myoclonus, “Chewing gum fits”
“Old Dog” encephalitis (chronic)
• Slowly progressive
• Less seizures, myoclonus
• Circling, compulsive walking, blindness, paralysis
Rabies Virus (Lyssavirus); exposure, portal, histo, incubation period, 3 main clinical manifestations
Exposure
• Bite wounds
Portal
• Retrograde axonal transmission
Histo
• Nonsuppurative encephalitis
• Negri bodies: intracytoplasmic inclusion bodies
• Use fresh brain
Incubation Period
• 1-8wks
3 Main Clinical Manifestations
• Prodromal ->
• Furious/excitatory ->
• Dumb/Paralytic
West Nile Virus (Flavivirus); basics, gross, histo, clinical signs
- Infects Birds, horses, people
- Transmission by mosquitos
- Viremia -> hematogenous spread to CNS
Gross
• Multifocal petechiae, esp gray matter of brainstem and spinal cord
Histo
• Non-suppurative polioencephalomyelitis
Clinical Signs
• Fever, depression,
• Ataxia
• Paresis- paralysis
Differential Diagnosis for horses w/ Acute nonsuppurative meningoencephalomyelitis
- West Nile Virus
- Eastern Equine Encephalitis,
- WEE, VEE
- Equine Herpesvirus
- Rabies Virus
- Equine Protozoal Myelitis
Fungal Dz of the CNS; basics, common Dzs, Portal
- Granulomatous Inflammation
- Often part of systemic infection
- Often forms a mass-like lesion
Common Fungal Dz • Cryptococcus felis/neoformans • Blastomycosis dermatitidis • Histoplasma capsulatum • Coccidiodes immitus
Portal
• Inhaled-> lungs -> hematogenous -> CNS
• Direct nasal extension
Cryptococcocus neoformans; basics, portal, gross/histo lesions
- Primarily infects cats
- Thick mucopolysaccharide coat protects from immune response
Portal
o Direct extension from nasal infection
o hematogenous secondary to pulmonary infection
Gross
o “Cysts in the brain”
Histo
o Many organisms
o +/- inflammation
Toxoplasma gondii; basics, pathogenesis, gross, histology, clinical signs
- Results in disseminated dz, CNS infection, or abortion
- definitive host (full life-cycle) = cats
- Immunocompromised hosts
Pathogenesis in intermediate hosts o Hematogenous to CNS-> o infects endothelial cells + leukocyte trafficking -> o Form cysts in brain -> o tachyzoites rupture out -> o necrosis and inflammation
Gross
o none to small foci of malacia/hemorrhage
Histology
o necrosis, gliosis, protozoal organisms
Clinical signs
o Seizures, paresis, weakness, depression, circling, blindness, ataxia
Neospora cranium
- Similar to toxoplasma
- Definitive host = dogs
- CNS dz in dogs
- Abortion in cows
- Diagnostic: IHC, PCR
Two Types of Parasitic CNS Diseases
Migration in aberrant host
• EX: Larvae of Baylisascaris procyonis (round worm of raccoons) -> CNS disease in dogs (and humans)
Normal host w/ aberrant migration
Prions - Transmissible Spongiform Encephalopathies; High efficacy transmission V Low efficacy
• Very long incubation period (only seen in adults)
High Efficiency Transmission
• Animal to animal spread common (ingestion at birth)
• Ex: CWD, Scrapie
Low Efficiency Transmission
• No animal to animal transmission
• Ex: BSE - transmitted by contaminated feedstuffs
Prions - Transmissible Spongiform Encephalopathies; pathogenesis, histo, clinical signs in sheep deer cattle
Pathogenesis
• Ingestion ->
• proliferates in lymphoid tissue ->
• splanchic nerves & retrograde axonal transport ->
• spinal cord and brain ->
• gradual accumulation of abnormal prion protein in astroglia and neurons
Histo • Vacuolar degeneration of neurons • Neuronal loss • Astrogliosis • NO inflammation
Clinical Signs Sheep o Scrapie o Severe pruritis = wool loss, weight loss, incoordination o Genetic resistance/susceptibility
Elk and Deer
o Chronic Wasting Disease
Cattle
o BSE/ “Mad cow disease”
o Hyperexcitability, incoordination, aggressiveness
Granulomatous meningoencephalitis; who gets it, gross, histo
• Typically young, small breed dogs
Gross
o Focal - presents as mass lesion
o Disseminated - typically progressive, multifocal signs
Histology
o Angiocentric to coalescing
o Macrophages and lymphocytes (nonsuppurative)
o Commonly in brainstem and midbrain
Necrotizing Encephalitides; two types, who gets it, clinical signs, gross, histo
- necrotizing meningoencephalitis,
- necrotizing leukoencephalitis
- young small breed dogs
- overlapping neuropathology
Clinical signs
o Multifocal & variable
o seizures, depression, circling, vestibular-cerebellar, visual deficits, death
o Rapidly fatal
Gross
o Necrotizing lesions & Cavitation
o NME- cerebral cortices and meninges
o NLE- periventricular white matter, brainstem
Histology
o Necrosis + non-suppurative inflammation
MUE
o meningoencephalitis of unknown origin
o used when animal is still alive
o refers to:
- necrotizing meningoencephalitis,
- necrotizing leukoencephalitis
- Granulomatous meningoencephalitis
Thiamine Deficiency in Ruminants; basics, gross, histo, clinical signs
o B1 via microbes in rumen
o Changes in ruminal flora due to acidodis = thiaminase producing bacteria
o Thiaminase containing plants (Bracken fern, horsetail)
o Ingestion of sulfur (corn, sugar cane)
o results in polioencephalomalacia
Gross
• Necrosis cerebral hemispheres (if severe)
• Autoflourescence
Histo
• Laminar cortical necrosis
Clinical Signs
• ataxia, cortical blindness, seizures, death
Thiamine Deficiency in Carnivores; basics, gross, histo, clinical signs
o need B1 in diet o Fish containing thiaminases o Decreased thiamine intake o Excessive heating of foods o Preservation of meat with sulfites o Upper GI disease causing decreased absorption o results in polioencephalomalacia
Clinical Signs
• Depression, anorexia, neck ventroflexion, ataxia, paresis, seizures
Gross
• Malacia- Caudal colliculi, bilaterally symmetric
Histo
• Neuronal necrosis
• Neuropil vacuolation/gliosis
DfDx for Polioencephalomalacia in ruminants
- Changes in ruminal flora
- Thiaminase containing plants
- Sulfur toxicity
- Lead toxicity
- Water deprivation/Salt toxicity
Clostridium perfringens type D Enterotoxemia; basics, pathogenesis, clinical signs, gross, histo
- Pulpy kidney disease or overeating disease
- GI tract bacteria produce TOXIN = Neurologic disease
- Sheep»_space;> goats > cattle
Pathogenesis o Change in feed -> o Intestinal overgrowth of C. perfringens type D -> o production of EPSILON TOXIN -> o damages endothelium -> o edema and ischemic necrosis
Clinical Signs
o Death
Gross
o Bilaterally symmetric (leuko) encephalomalacia
o Autolysis (Pulpy kidney)
Histology
o Vascular degeneration and necrosis
o Edema
o Secondary necrosis
Nigropallidal Encephalomalacia in Horses ; cause, gross, histo, clinical signs
• Caused by yellow starthistle or Russian knapweed
Gross
o Globus pallidus/substantia nigra
o Malacia
Histo
o Neuronal necrosis
o Neuropil vacuolation
Clinical Signs
o Acute presentation after chronic grazing
o Persistent chewing movement and difficulty prehending food/swallowing
o Death due to progressive starvation/emaciation
o Depression, somnolence
Leukoencephalomalacia in Horses; cause, gross, histo, clinical signs
• “moldy corn poisoning” = mycotoxin
Gross
o Malacia in the white matter of the cerebrum
Histo
o Necrosis & vacuolation
Clinical Signs
o Depression, head pressing, aimless wandering, blindness, seizures
Concussion V Contusion
Concussion:
o temporary loss of consciousness following head trauma
o diffuse change w/ no detectable lesions
Contusion
o Focal brain injury - hemorrhage
o Coup and contrecoup lesions
Acute Brain Swelling & Infarcts
Acute brain swelling
o Not cerebral edema
o unregulated vasodilatation following trauma
Infarcts
o Thrombosis or embolism in the cerebrospinal arterioles.
Cerebral edema; 4 types, gross lesions
• Causes loss of blood brain barrier
Vasogenic Edema
o leaky vessels
o Fluid w/in extravascular/extracellular space
Cytotoxic Edema
o intracellular edema
Hydrostatic Edema
o increased CSF pressure
o Fluid w/in periventricular space (whitematter)
Hypo-osmotic edema
o Over consumption of water, loss of sodium
o Fluid w/in extracellular and intracellular spaces
Gross
o Flattening of the sulci and gyri
o Transtentorial herniation of the cerebrum
o Herniation of the cerebellum through foramen magnum
Cerebellar Hypoplasia; gross, histo, clinical signs
- Usually secondary to in utero viral infections
- Panleukopenia (parvovirus) in cats or BVD in cattle
Gross
o Small cerebellum
Histo
o Loss of external granular layer
Clinical Signs
o Often aborted
o Vestibular signs
Cerebellar Abiotrophy
- Similar to hypoplasia, but loss of Purkinje cells occurs AFTER birth
- Rare
Clinical signs
o after about 4 months of age
o progressive
o Ataxia, vestibular dysfunction
Hydrocephalus
• fluid within ventricular system
Congenital
o Genetic disorders
o Inflammation with in utero infections
Acquired
o After birth: inflammation, neoplasia
Hepatic encephalopathy
- Liver failure or PSS
- Toxins absorbed by GI tract
- Alteration in transmembrane movement of amino acids, water and electrolytes
- Inhibit action potentials in neurons
Clinical Signs o Most severe after eating o Depression o Vomiting o Head Pressing o Seizures
Lyposomal Storage Dz
- Disruption of lysosomal degradation
- Genetic or toxic
- Accumulation of products -> cellular dysfunction & death
Histo
o Swollen neurons
CNS Neoplasia
Meningioma
o Most common
o Arises from meninges
Astrocytoma, Oligodendroglioma
o Difficult to distinguish grossly
o Aggressiveness varies
Ependymoma
o Cells lining ventricles
o Causes secondary hydrocephalus
Metastatic Tumors
o Hematogenous or direct extension
Equine Protozoal Myelitis; cause, gross, histo, clinical signs
Cause
o Sarcocystis neurona from oppossum feces
Gross
o Multifocal, random necrosis/hemorrhage
Histo o Gray and white matter (random) o Necrosis and hemorrhage o Mixed inflammation o Gliosis o parasitic cysts
Clinical Signs
o Ataxia
o Muscle atrophy
o Urinary incontinence
Spinal Fractures & Trauma
- May cause shearing
- May cause hemorrhage
- May cause compression and damage
- Wallerian degeneration of axons will occur cranial and caudal to site of trauma
Cervical Stenotic Myelopathy; gross, histo, clinical signs
- Wobbler’s Dz
- Young large breed dogs & horses
Gross
o May see narrowed spinal canal
o Radiography is often more sensitive than necropsy
Histo
o Wallerian degeneration
Clinical Signs
o Paresis and ataxia of all 4 limbs
o Loss of conscious proprioception
Static
o narrow spinal canal
Dynamic
o spinal canal narrows depending on position of head
Intervertebral Disc Dz; types, gross, histo, clinical signs
- Dogs
- Degeneration of intervertebral disc
- Severity depends on amount of compression & speed it occurs
Type 1
o Degeneration of nucleus pulposus
o Rupture & extrusion of disc material
o usually acute
Type 2
o Degeneration of annulus fibrosus
o Weakening & protrusion of disc
o usually chronic
Gross
o Extrusion or protrusion of disc into spinal canal
o +/- collapse of the disc space
Histo
o Wallerian degeneration
Clinical Signs
o Pain
o Paresis
o Paralysis
Fibrocartilagenous Emboli (FCE); gross, histo, clinical signs
• Fibrocartilage from nucleus pulposus in vessels causes infarction in spinal cord
Gross
o Infarction
Histo
o Fibrocartilage evident in vessels
Clinical Signs
o Acute onset
o Paresis/Paralysis
Basics of Syringomyelia & Spinal Bifida
Syringomyelia • Cyst in spinal cord filled with CSF Spinal Bifida • Failure of closure of spinal canal during development
Spinal Cord Neoplasias
Uncommon
• Meningiomas
• Gliomas
• Thoracolumbar spinal cord tumors
Acute Idiopathic Polyradiculoneuritis (Coonhound Paralysis); what is it, histo, clinical signs
• Inflammation of peripheral nerve and spinal roots
1-2 weeks following “exposure” • Raccoon bites • Vaccination • Campylobacter • Suspected autoimmune
Histo
• Degeneration & inflammation of peripheral nerves
Clinical signs • Progressive paresis -> paralysis • Bladder/bowel/tail movements normal • Death may occur via respiratory paralysis • May recover with supportive care
Colonic Aganglionosis (lethal whit foal syndrome)
- Foals born w/o myenteric & submucosal ganglia in colon
* Born normal, soon die due to atony of colon and failure to pass feces
Peripheral Nerve Neoplasia
- Schwannoma (schwann cells)
- Peripheral Nerve Sheath Tumor (fibroblasts)
(these are soft tissue sarcomas)
Clostridium Tentani (tetanus); what is it, clinical signs
- Enters nerve endings near wound -> retrograde axonal transport to CNS -> neural-neural junctions
- Prevents release of neurotransmitters by inhibitory interneurons
- Horses, cows, sheep»_space;> dogs & cats
Clinical Signs • Muscle rigidity/stiffness • Hyperesthesia • Hyperreflexia • Muscle spasticity and hypertonia • Colic
Clostridium Tentani (tetanus) Pathogenesis
- Endospores ubiquitous in environment ->
- Wound ->
- anaerobic conditions ->
- vegetative form ->
- neurotoxins (tetanospasmin) ->
- Toxin released when bacterial dies
- Binds at NMJ ->
- Absorbed and transported via axon to spinal cord ->
- Crosses synapse to presynaptic inhibitor neuron ->
- Blocks release of inhibitor neurotransmitters ->
- Loss of inhibition -> rigidity and hyperreflexia
Clostridium Botulinum (botulism)
- Ingestion of feed contaminated w/ toxin
- Toxin binds receptors on presynaptic terminals of peripheral cholinergic synapses
- Toxin is taken up by the neuron and blocks release of acetylcholine
- Results in flaccid paralysis
Myasthenia Gravis
- blockade of signaling at neuromuscular junction ->
- Weakness and atrophy of skeletal muscles and/or esophagus
Autoimmune
• Abs to acetylcholine receptors
• Idiopathic or paraneoplastic
Congenital
• Deficiency of acetylcholine receptors
