Cardiovascular and Muscle

3 Reasons why heart failure is less common in animals than humans

1. Lipid abnormalities are very rare in animals (and even high cholesterol → low risk of cardiac disease)

2. Idiopathic hypertension is rare in animals

3. 2˚ hypertension is less significant the the 1˚ lesion (eg. CKD will kill before hypertension)

Structure and Function of the Heart

• Left vs. right side

• 4 Chambers (+ functions)

• 4 Valves (+ functions)

L vs. R: Left side must pump blood to a more extensive capillary bed in the systemic circulation vs. the lungs for the right side of the heart

• Systemic BP 3x pulmonary BP → L side of heart 3x bigger than R side to generate the higher BP

Chambers:

1. Right Atrium = Collects deoxygenated blood from systemic circulation

2. Right Ventricle = Pumps blood through lungs

3. Left Atrium = Collects oxygenated blood from lungs

4. Left Ventricle = Distributes oxygenated blood to systemic circulation

Valves: Cusps (flap of fibrous tissue) attached to papillary muscles by chordae tendinae which prevent backflow of blood

1. Right AV = Prevents backflow into RA

2. Pulmonic = Prevents backflow into RA

3. Left AV = Prevents backflow into LA

4. Aortic = Prevents backflow into LV

Describe THREE layers of the heart

1. Endocardium = Single layer of endothelium with small amounts of fibrous connective tissue for protection

2. Myocardium = Myocytes arranged in spiral bundles which form a highly efficient pump

   • Thickness depends on pressure required to pump blood

   • Most richly vascularised muscle in body (supplied by coronary arteries) = 1 capillary/myocyte

   • Exclusive reliance on oxidative metabolic

3. Epicardium = Outer layer of heart made of fibrous tissue attached to the visceral layer of the pericardium

Describe THREE features to observe during necropsy of the heart

1. Colour

   • Pale myocardium = Necrosis/fibrosis

   • Caution: PM muscle contraction (rigor mortis) → Squeezes blood out of myocardial vessels which produces pallor

     • Slice into myocardium: Pallor extending into lumen and papillary muscles = TRUE necrosis/fibrosis

2. Thickness of chamber walls and shape of heart

   • Normal: LV wall 3x thicker than RV wall due to pressure differences

   • Abnormal: LV wall = RV wall (1:1) (systemic and pulmonary BP are similar)

     • DDx: L → R shunt (eg. PDA, VSD, ASD) OR PS, pulmonary hypertension

   • Abnormal: LV > 3x RV wall (5:1)

     • DDx: SAS or HCM

3. Valves

   1. Patency

   2. Ensure valves are convex

   3. Jet lesions

Response of heart to injury (6 steps)

1. Injury to myocardiocytes

2. Myocardium poorly heals via fibrosis ONLY (cannot regenerate)

3. Fibrosis reduces elasticity and contractility of the heart resulting in impaired BP necessary to pump blood forwards

4. 3 - 5 fold functional reserve of heart by 6 compensatory mechanisms

   1. Increase HR

   2. Atrial dilation to increase venous return

   3. Myocyte hypertrophy to increase contractility

   4. Increased blood volume via RAAS

   5. Increased peripheral resistance (vasoconstriction)

   6. Redistribution of blood flow

5. CHF develops when compensatory mechanisms fail and the heart cannot propel sufficient blood

6. Cardiac decompensation = Final stage of heart disease where marked dilation and severe thinning of the heart walls prevents contractility to match (Starling's law no longer maintained) → Rapid progression of cardiac disease and death

Define congestive heart failure (CHF) and effects on forward vs. backward failure

• Clinical syndrome caused by a variety of chronic conditions that reduce heart function

• Develops as the heart cannot adequately propel blood forwards

• Little effect on CO and organ perfusion

  • Heart disease does NOT cause CKD

• Significant effects caused by backing-up of blood behind the heart which cannot pump blood out fast enough

What is this?

• 2 Causes (+ DDx)

• Pathogenesis

• 2 Clinical signs

LCHF = Pulmonary oedema

Causes:

1. Dysfunctional LAV or AoV (endocardiosis) → Regurgitation/insufficiency

2. Left ventricular myocardial necrosis → Weakness (myocarditis or fibrosis)

Pathogenesis:

1. Left side of the heart cannot adequately propel blood into systemic circulation

2. Blood collects in pulmonary circulation → pulmonary congestion

3. Increased pulmonary HP causes fluid to leak from pulmonary capillaries → Pulmonary oedema

   • Pulmonary Oedema (foam on cut surface with swollen, wet and shiny lungs) = Acute LCHF

4. Increased permeability results in leakage of RBCs into alveoli

5. Alveolar macrophages enter the alveolar space to engulf this material

6. Haemosiderin is produced and stored in alveolar macrophages as a result of RBC breakdown

   • Heart Failure Cells = Alveolar macrophages containing granules of haemosiderin formed from RBC breakdown and indicates haemorrhage into the alveolar space

   • Tan lungs = Chronic LCHF

Clinical Signs:

1. Exercise intolerance

2. Nocturnal cough

What is this?

• 4 Causes (+ example DDx)

• Pathogenesis

• 3 Outcomes

RCHF = Nutmeg liver and brisket oedema

Causes:

1. Cor pulmonale = RCHF that develops 2˚ to pulmonary hypertension → Increased afterload

   • Right side of the heart cannot generate sufficient force to propel blood through pulmonary circulation resulting in RCHF

   • DDx:

     1. 2˚ to LCHF (pulmonary hypertension due to congestion)

     2. Equine heaves (high intrathoracic pressure)

     3. Pulmonary fibrosis (high intrathoracic pressure)

2. Heart-filling defects (eg. pericardial effusion)

3. Dysfunction of the pulmonic or right AV valves (endocardiosis)

4. Right ventricular myocardial necrosis (myocarditis or fibrosis)

Pathogenesis:

1. Right side of heart cannot adequately propel blood into pulmonary circulation fast enough

2. Allows blood to collect in systemic circulation → systemic congestion

3. Systemic hypertension

Outcomes:

1. Oedema

   • Dog = Ascites

   • Cat = Hydrothorax

   • LA/horse = Brisket oedema and bottlejaw

   • Anasarca uncommon (do not live long enough for oedema to develop in all cavities AND SC)

2. Congestion of kidneys

   1. Systemic venous congestion results in renal congestion

   2. Reduced blood flow through the juxtaglomerular apparatus results in RAAS activation to increase GFR

   3. RAAS promotes Na+ retention in the tubules which increases blood volume

   4. Attempts to restore CO BUT exacerbates CHF instead due to volume overload → Oedema

3. Nutmeg liver

   1. Congestion of systemic circulation

   2. Dark red blood accumulates in the centrilobular veins of the liver which contrasts with the pale peripheral parts of the lobule (nutmeg liver)

   3. As more blood accumulates, pressure in the central veins increases which causes adjacent hepatocytes to atrophy or die

   4. Hepatocyte death results in cirrhosis (fibrosis of central vein)

   5. Haemosiderin is also found within local macrophages as a result of RBC breakdown

What is this?

TWO types

Cardiac Hypertrophy (no hyperplasia as cardiac cells cannot regenerate)

Types:

1. Physiological hypertrophy (4) = Normal myocardial hypertrophy in response to increased exercise (eg. racehorse or greyhounds) which does NOT cause pathological changes

2. Pathological hypertrophy (4) = 1˚ OR 2˚

   1. 1˚ = Disorder of the myocardium (eg. idiopathic HCM)

   2. 2˚ = In response to non-myocardial disease process (eg. subaortic stenosis or hyperthyroidism)

Is there sufficient CK and AST leakage form cardiac muscle ONLY to detect disease on biochemistry?

NO! Many cardiocytes must die to detect → Death

proBNP

• Definition

• 3 Causes of elevation

• 2 Disadvantages

• 2 Indications

Definition: Natriuretic peptide secreted by the heart to maintain fluid balance and BP regulation in response to:

1. Volume overload

2. Cardiac hypertrophy

3. Hypoxia

-ve:

1. Blood must be collected in a special pink-top tube containing protease inhibitor → Refrigeration → Sent to lab on SAME day

2. Cannot screen for myopathies without clinical signs of CHF (i.e. proBNP cannot distinguish between healthy patients and HCM cats with no CHF)

Indications:

1. Dogs or cats presenting with respiratory signs to distinguish between 1˚ respiratory disease (eg. chronic bronchitis) or heart failure

2. Analysing efficacy of treatment for heart failure

Best way to observe congenital heart defects PM

Fresh tissue specimens (formalin causes myocardial contraction making it impossible to observe subtle lesions associated with congenital disorders)

THREE types of congenital/genetic cardiac disorders

• DDx for each

• Most common DDx in dog vs. cat vs. cow vs. pig

Types:

1. Failure of foetal structures to close (4)

   1. Patent Ductus Arteriosis (PDA)

   2. Atrial Septal Defect (ASD)

   3. Ventricular Septal Defect (VSD)

   4. Tetralogy of Fallot (TOF)

2. Abnormal valve development (4)

   1. Pulmonic stenosis (PS)

   2. Subaortic stenosis (SAS)

   3. Congenital valve malformations

   4. Valvular haematocyst

3. Abnormalities in large blood vessels (3)

   1. Persistent right aortic arch (PRAA)

   2. Transposition of aorta and pulmonary artery

   3. Ectopia cordis

Species Variation:

• Dog = PDA, PS, SAS, PRAA

• Cat = VSD, LAV malformation

• Cow = ASD, VSD, transposition of aorta

• Pig = SAS, VSD

Normal blood flow through a foetal heart and changes after birth

In utero: Blood shunted from R → L side of circulation allowing bypass of pulmonary circulation via

1. Ductus arteriosus = Connects the PA to the Ao

2. Foramen ovale = Opening between the LA and RA

Birth: Shunts close due to BP changes caused by lung inflation

• Ligamentum arteriosum = Remnant of the ductus arteriosus which becomes non-patent at birth

What is this?

• Signalment

• Pathogenesis

• 3 PM features

Patent Ductus Arteriosus (PDA)

Signalment: Dog (esp. female poodle)

1. Ductus arteriosus remains patent at birth (should become the non-patent ligamentum arteriosum)

2. Blood is allowed to travel from the higher pressure Ao → lower pressure PA

3. Increased blood in pulmonary circulation → Pulmonary hypertension and decreased systemic BP

4. BP right side of heart = BP left side of heart

5. Increased RV wall thickness to pump blood through increased afterload → Absence of 3:1 ratio

PM:

1. Dilated ductus arteriosus

2. Absence of 3:1 ratio of LV:RV thickness (1:1) resulting in loss of heart apex normally produced by enlarged LV wall

3. Fibrosis in later stages of disease

What is this?

• Pathogenesis

• PM

Atrial Septal Defect (ASD)

Pathogenesis:

1. Foramen ovale fails to close at birth/incomplete atrial septum development

2. Blood shunts from high-pressure LA to low-pressure RA resulting in pulmonary hypertension

3. BP between right and left side of heart are equal

4. Absence of 3:1 ratio (1:1 ratio)

PM: 1:1 ratio of LV:RV

What is this?

• Pathogenesis

• Location

• PM

• Clinical signs

Ventricular Septal Defect (VSD)

Pathogenesis:

1. Incomplete development of ventricular septum

2. Blood shunts from high-pressure LV to low-pressure RV

Location: Defect immediately below AV valves

PM: 1:1 ratio of LV:RV

Clinical Signs: More severe shunting = More severe clinical signs

Tetralogy of Fallot

• 4 Cardiac abnormalities

• Pathogenesis

• 3 Clinical signs

• Prognosis

Abnormalities:

1. Ventricular septal defect

2. Pulmonic stenosis

3. Transposition of the aorta (shifted to the right and shares the LV and RV)

4. 2˚ Right ventricular hypertrophy

Pathogenesis:

1. Pulmonic stenosis prevents blood flow through the pulmonary artery

2. This causes blood to flow from the the RV → VSD and aorta via aortic transposition (opposite from other congenital defects)

3. 2˚ RV hypertrophy required to pump the blood into the high-pressure left ventricle through the VSD

4. Results in poorly oxygenated blood from RV being pumped into systemic circulation

Clinical Signs:

1. Cyanosis due to deoxygenated blood in systemic circulation (vs. other diseases with high O2 blood through body)

2. Dependent oedema

3. Nocturnal cough due to pulmonary oedema NO PAIN

Prognosis: Better to have ToF than VSD

What is this?

• Pathogenesis

• 4 PM features

Pulmonic Stenosis (PS)

Pathogenesis:

1. Narrowing of the RV outflow channel → Increased RV pressure

2. 2˚ RV hypertrophy required to generate enough blood pressure to squeeze blood through narrow valve

3. High pressure blood squirts from the stenotic pulmonic valve which causes dilation of the pulmonary artery and jet lesions

4. Dilation → slow blood hit by fast blood from squirting PS = turbulence and thrombosis formation

5. ± Developing signs of RCHF with age depending on severity of PS as RV cannot pump blood forward fast enough

PM:

1. RV hypertrophy

2. Jet lesions in the pulmonary artery

3. Pulmonary artery dilation

4. ± RCHF (systemic hypertension)

What is this?

• Pathogenesis

• Onset

• 5 PM features

Subaortic Stenosis (SAS)

Pathogenesis:

1. Thick fibrous band below the aortic valve (defect in the endocardial cushions) narrows the outflow channel of LV → Increased LV pressure

2. 2˚ LV hypertrophy required to generate enough blood pressure to pump blood to systemic circulation

3. High pressure blood squirts from the stenotic aortic valve which causes dilation of the aorta and jet lesions

4. Dilation → slow blood + fast blood from squirting SAS = turbulence and thrombosis formation

5. Thromboembolism travels through the coronary artery openings resulting in multifocal myocardial infarction

6. ± Developing signs of LCHF due to failure of LV hypertrophy or sudden death due to myocardial infarct

Onset: May develop normally into adulthood before signs of CHF develop

PM:

1. LV hypertrophy (*)

2. Jet lesions in the aorta

3. Dilation of the aorta (green)

4. Multifocal myocardial infarction

5. ± LCHF (pulmonary hypertension) NO kidney failure

Congenital Valve Malformations

• Prevalence

• Aetiology

Prevalence: Less common cause of reduced patency

Aetiology: Heritable syndromes of the left or right AV malformation reported in dogs and cats

What is this?

• Definition

• Signalment

• Prognosis

Valvular Haematocyst

Definition: Blood-filled cysts in calves

Signalment: Common in young ruminants

Prognosis: NOT serious and spontaneously regress after several months with no clinical signs

What is this?

• Normal development

• Pathogenesis

• Clinical signs

Persistent Right Aortic Arch (PRAA)

Normal: In utero, foetus has L and R aortic arch → Regression of right aortic arch after birth

• Normal: L = Ao → PA → Oesophagus = R

• PRAA: L = PA → Oesophagus → Ao = R

Pathogenesis:

1. Persistent right aortic arch and regression of the left aortic arch in embryo

2. Oesophagus between the pulmonary artery and the aorta

3. Because the two vessels are on opposite sides of the oesophagus, contraction of the ligamentum arteriosum compresses the oesophagus

4. Chronic regurgitation leading to megaoesophagus proximal to constriction

Clinical Signs: No signs of heart disease (blood flow normal)

• Chronic regurgitation beginning at weaning due to transition to solid foods which cannot pass through

• Death due to aspiration pneumonia

Transposition of the AO and PA

• 3 Types

• Prognosis

Types: Aorta or pulmonary artery are attached to the heart at an aberrant location

1. BOTH arteries in the same ventricle (eg. aorta and pulmonary artery originating from the RV)

2. One artery within BOTH ventricles (eg. Tetralogy of Fallot)

3. Arteries swap ventricles (eg. aorta originates from RV and pulmonary artery originates from LV)

Prognosis: Grave due to marked BP abnormalities → Death at birth or immediate post-natal period as incompatible with life

What is this?

Ectopia Cordis

Rare congenital disease of calves where the heart is located outside the thoracic cavity (entirely outside body or under skin) Calves may survive a few days if under skin

Cardiac Diseases

• 5 Pericardial DDx

• 4 Endocardial DDx

• 5 Myocardial DDx

• 2 Neoplastic DDx

Pericardial DDx:

1. Pericarditis (4)

2. VitE/Se deficiency (4)

3. Haemopericardium (3)

4. Enterotoxaemia (4)

Endocardial DDx:

1. Endocardial mineralisation (3)

2. Valvular endocardiosis (5)

3. Atrial thrombosis (3)

4. Endocarditis (4)

Myocardial DDx:

1. Nutritional deficiencies

2. Toxicity

3. Physical injury and shock

4. Hypertrophic cardiomyopathy (HCM)

5. Dilated cardiomyopathy (DCM)

Neoplastic DDx:

1. RA HSA in dogs (3)

2. Lymphoma in cattle (3)

Overview of the Pericardium

• Normal anatomy (+ function)

• 2 Causes of reduced ventricular filling

Normal: Contains small amount of lubricating fluid to allow contraction and passive filling/relaxation of the heart

Causes of Reduced Ventricular Filling:

1. Pericarditis

2. Cardiac tamponade = Excessive fluid accumulation in the pericardial sac which compresses the heart and prevents it from fully relaxing/filling with blood

What is this?

• Definition

• Aetiology

• DDx

  • Pathogenesis

  • 3 Clinical signs

Purulent Pericarditis = Degenerate neutrophils in pericardial sac

• Chronic = Organisation of adhesions

Aetiology: Pyogenic bacteria

DDx: Bovine Traumatic Reticulopericarditis (aka. Hardware Disease)

1. Cow ingests foreign body (eg. nail) which contains pyogenic bacteria on the surface

2. Peristaltic contraction pushes the foreign body from the reticulum → diaphragm → pericardium

3. Pyogenic bacteria colonise the pericardial sac

4. Cow often survives months before succumbing to RCHF or septicaemia

Clinical Signs: Present with RCHF due to defective heart filling

1. Dependent oedema (bottlejaw and brisket oedema)

2. Nutmeg liver

3. Anorexia and weight loss

What is this?

• Definition

• Aetiology

• 4 DDx

• Pathogenesis

Fibrinous Pericarditis = Increased pericardial fluid containing flecks of fibrin

Aetiology: Haematogenous spread of non-pyogenic bacteria deposits in serous membranes → Fibrinous polyserositis (eg. pericarditis, arthritis, peritonitis, pleurisy)

DDx:

1. Pig = Haematophilus parasuis (Glasser's disease)

2. Horse = Streptococcus zooepidemicus

3. Cattle = Histophilus somni

4. Cat = FIP due to systemic vasculitis

Pathogenesis:

1. Bacteria in blood aggregate in serosal blood vessels of the pericardium and cause damage

2. Results in leakage of fibrin into the pericardial sac which forms adhesions between parietal and visceral pericardium

3. Mature fibrin contracts causing the heart to constrict which prevents adequate filling

4. Results in RCHF ± LCHF

5. Chronic fibrinous pericarditis = Organisation of adhesions

Bread-and-butter heart = Severe fibrinous pericarditis containing large aggregate of fibrin attached to the pericardial surface

What is this? (pig heart)

• Aetiology

• Pathogenesis

• Outcome in other species

Mulberry Heart Disease

Aetiology: Vitamin E/Se deficiency

Pathogenesis: Oxidative damage to myocardial endothelial cells → Leakage of blood and fibrin → Red discolouration from pericardial fluid

Other Species: Myocardial necrosis and mild increased pericardial fluid with small amounts of fibrin (same effect as skeletal muscle)

Haemopericardium (3)

• 2 DDx in dogs

• DDx in pigs/horses

• Prognosis

Dog:

1. Ruptures RA haemangiosarcoma

2. Idiopathic haemopericardium (slower onset with signs of CHF)

Pig/Horse: Spontaneous rupture of proximal Ao

1. Connection of the proximal aorta to LV is weak

2. Strenuous exercise results in increased intracardiac pressure

Prognosis: Blood must be pumped under pressure into the pericardial sac → Rapid/spontaneous death

What is this? (lamb heart)

• Signalment

• Agent

• Pathogenesis

• PM features

Enterotoxaemia (4) aka. Pulpy kidney or overeating disease

Signalment: Young, rapidly growing lambs

Agent: Overgrowth of commensal = Clostridium perfringens Type D

Pathogenesis:

1. Increased CHO intake allows excess to spill into the proximal duodenum resulting in overgrowth of Cl. perfringens

2. Bacteria produce toxins which are absorbed into the bloodstream from the intestinal wall

3. Toxins travel around the body causing vascular damage

4. Damaged blood vessels leak fibrin throughout the body which is easiest to view in the pericardial sac as the smallest enclosed space of the body

PM:

1. Large fibrin clot in the pericardium = Only gross lesion highly suggestive of disease

2. Histology of brain = Definitive diagnosis

3. Renal autolysis = NOT specific for pulpy kidney as caused by high fever at death and stress-induced glucosuria

What is this?

TWO causes

Endocardial Mineralisation (3) → No effect on heart function

Causes:

1. Cattle = Chronic debilitation (eg. Johne's Disease) → Endocardial fibrosis and mineralisation

2. Jet lesions = Focal mineralisations of the perivalvular endocardium caused by blood turbulence that results from insufficiency/regurgitation (squirts of blood hitting the endocardium)

What is this?

• Signalment

• Location

• PM

• Pathogenesis

• Clinical signs

Valvular Endocardiosis (5) aka. Myxomatous mitral valve disease (MMVD)

Signalment: Almost all dogs >10yr have some degree of endocardiosis (most have no clinical signs)

• #1 cause of CHF in dogs

• Esp. CKCS

Location: LAV > RAV » Ao and PA

PM: Valves are smooth, shiny and nodular (vs. endocarditis)

1. ± Atrial dilation

2. ± Atrial jet lesions

Pathogenesis:

1. Mucoid or myxomatous degeneration of collagen fibres within valve cusps

2. → Shortened cusps with areas of nodular thickening

3. Loss of valve patency and reduced function → Regurgitation

4. Backflow of blood from ventricle to atrium → Compensatory atrial dilation and endocardial jet lesions

5. LCHF (left AV valvular endocardiosis)

Clinical Signs:

1. Asymptomatic

2. Nocturnal cough and exercise intolerance with LCHF

Atrial Thrombosis (3)

• Pathogenesis

• DDx

Pathogenesis:

1. 2˚ due to change of heart size, usually atria (eg. cardiomyopathy) OR any loss of patency of AV valves (eg. endocardiosis)

2. Results in slow and turbulent blood flow through the atria that is more likely to clot

3. Atrial thrombus impairs heart function and may result in rapid death if large

4. Pieces of smaller clots break off → Thromboembolism and infarction elsewhere in body

DDx: Feline HCM → Atrial dilation → Atrial thrombosis → Saddle embolism

What is this?

• Signalment

• PM

• Histology

• 2 Risk factors

• 3 Outcomes

Valvular Endocarditis (4)

Signalment: Young production animals (more bacteria circulating the body)

PM: Large, yellow-grey, rough nodular vegetations (cauliflower appearance)

Histology: Layers of fibrin, trapped RBCs, bacteria and neutrophils

Risks:

1. More circulating bacteria from elsewhere in the body (eg. pneumonia or abscess)

2. Valvular turbulence (normally disrupts laminar flow allowing bacteria to strike valve cusps)

Outcomes:

1. ACUTE = Large vegetations prevent normal valve function and may block the valve orifice → Rapid death

2. Pieces of vegetations may break off forming multiple septic emboli

   • L Side (LAV/Ao)

     1. Septic myocardial infarction (coronary arteries)

     2. Septic renal infarction

   • R side (RAV/PA) = Pulmonary abscessation

3. CHRONIC = Survival of endocarditis → Fibrin contraction on valves and healing by fibrosis → Valvular regurgitation and CHF

How does laminar flow prevent normal circulating bacteria from colonising the epithelium?

Blood at the edge of the vessel wall is very thin and low viscosity, while blood in the middle contains large and slow particles (eg. bacteria)

2 causes of myocardial infarct (stroke in animals)

1. Subaortic stenosis in dogs

2. Left-sided septic endocarditis

TWO myocardial infiltrations (2)

1. Adipocytes = Associated with obesity

2. Lipofuscin = Brown age pigment which accumulates in non-dividing cells

NEITHER associated with clinical signs

What is this?

• 2 Presentations

  • Clinical signs

  • PM

  • Histology

• 3 Causes (+ DDx)

Myocardial Necrosis (4)

Presentations:

Acute

Clinical Signs: Many myocytes affected → Acute necrosis and spontaneous death (rare in animals)

PM: White streaks of necrotic myocardium throughout

• Subtle and difficult to detect due to similar appearance to PM rigor mortis and myocyte contraction

Histology: Swelling, hypereosinophilic and loss of cross-striations in myocytes

Chronic

Clinical Signs: Fewer myocytes affected → Survival of acute necrosis and signs of CHF due to heart repairing by fibrosis which prevents strength of forward pumping of blood

PM: Yellow, dry, chalky if marked mineralisation present which is more obvious than the reparative phase

Histology: Macrophage infiltration, fibrosis and mineralisation

Causes:

1. Nutritional Deficiency

   1. VitE/Se = White muscle disease in lambs (RV) and calves (LV)

   2. Potassium

   3. Copper

   4. Thiamine

   5. Magnesium

2. Toxicity

   1. Ionophores (eg. monensin toxicity in horses when fed cattle-feed)

   2. Chemotherapy (eg. doxorubicin)

3. Physical Injury and Shock

   1. CNS lesions and trauma (heart-brain syndrome)

   2. Overexertion

   3. Electrical defibrillation

   4. Haemorrhagic shock

Cardiomyopathy (4)

• Definition

• 2 Aetiologies

• 2 DDx

Definition: Degenerative disease of the myocardium → Reduced heart function and altered blood flow → Sudden death or CHF

Aetiology:

1. Idiopathic 1˚ disease with heritable component (no underlying disease process)

2. 2˚ to another disease process (eg. feline HCM 2˚ to hyperthyroidism)

DDx:

1. Hypertrophic cardiomyopathy (HCM)

2. Dilated cardiomyopathy (DCM)

3. ± Feline endocardial fibroelastosis

What is this? (cat heart)

• 2 Aetiologies

• Signalment

• 4 Presentations

• 3 PM features

• Pathogenesis

Feline Hypertrophic Cardiomyopathy (HCM)

Aetiologies:

1. Idiopathic in younger cats

2. 2˚ to hyperthyroidism OR systemic hypertension with CKD in older cats

Signalment: Idiopathic = Male, large and ~4yr

• Canine HCM = Uncommon, large dogs present with sudden death

Presentations:

1. Sudden death due to:

   1. Reduced chamber volume → Little blood pumped out of ventricle chamber → Compensatory increased HR (>200bpm) → Fibrillation OR

   2. Thrombus blocks AV ostia

2. Die during GA = GA drugs strain CVS resulting in reduced compensatory HR → Increased CHF and reduced CO

3. Develop LCHF

4. Aortic thrombus (saddle emboli 20%) = Compensatory atrial dilation and AV dysfunction → Slow blood with turbulence in atrium → Atrial thrombosis → Aortic trifurcation → Infarct of hindlimbs

PM:

1. LV concentric hypertrophy (increased ventricular wall thickness) and reduced chamber volume

2. Compensatory dilated LA

3. AV valve disrupted and squashed together by hypertrophied ventricular myocardium

Pathogenesis:

1. Degenerative myocardium results in pressure overload due to reduced contractility

2. LV concentric hypertrophy results with compensatory dilated LA

3. Marked thickening of LV wall results in left AV valve dysfunction

4. Regurgitation of blood into dilated LA (heart murmur)

5. Results in turbulent and slowed blood flow → Atrial thrombosis → infarct of the brain, kidney and aortic trifurcation

What is this?

• Signalment (species, breed, sex, age)

• Aetiology

• Location

• Pathogenesis

• PM

Signalment: Large dogs (eg. Great dane), male, 5 - 7yr

• Also breed-specific Dobermans and Boxers

Aetiology: Idiopathic #1

• Cat = Taurine deficiency (grain-free diet) → Chylothorax (heart occludes thoracic duct)

Location: Variable (R/L/both)

Pathogenesis:

1. Ventricular chamber volume increases

2. Ventricular wall becomes stretched and thinner

3. Thin ventricular wall cannot generate sufficient blood pressure to pump blood

4. → RCHF/LCHF

5. Dilated ventricles → Predisposition to thrombi (eg. saddle thrombi)

PM: Globoid heart with chamber dilation and thinning of the ventricular walls (may collapse on PM)

Feline Endocardial Fibroelastosis

Signalment: Burmese and Siamese cats ~4m

Aetiology: Idiopathic or associated with previous endocarditis

Pathogenesis: Diffuse endocardial thickening with little myocardial damage → Reduced chamber volume

Cardiomyopathies in pigs/cattle

Pig: Idiopathic HCM and DCM reported

Cattle: Occasional DCM

Myocarditis (2)

ONE: VIRAL INFECTION

1. Canine Parvovirus

   • Signalment: Puppy <2w (vs. enteric form @ ~12w)

   • Prevalence: Very rare as puppies are rarely born without maternal Ab against CPV due to widespread virus or vaccine of dam OR exposed to CPV immediately after birth

   • Pathogenesis: Parvovirus only infects rapidly replicating cells and replication of the cardiac myocytes cease at 2w of age

   • PM: Diffuse heart pallor and flaccidity

   • Histology: Necrosis and lymphocytic inflammation with large intranuclear basophilic viral inclusions

   • Prognosis: Survival results in CHF with age due to increasing demand of the heart

2. Encephalomyocarditis Virus

   • Signalment: Rare cause of myocarditis of piglets ≤ 4m

   • Source: Enterovirus carried by rats

   • Region: Northern North Island of NZ #1

TWO: BACTERIAL INFECTION

Aetiologies:

1. 2˚ to bacteraemia

   1. Lambs with staphylococcal omphalitis

   2. ALL species with vegetative endocarditis

2. RARE 1˚ bacterial infection (healthy cardiac muscle is highly vascularised and difficult for bacteria to colonise)

   1. Clostridium chauvoei (cardiac blackleg)

   2. Mycobacterium tuberculosis

   3. Clostridium piliformis (Tysser's disease)

   4. Histophilus somni

THREE: PARASITIC INFECTION

1. Toxoplasma gondii

   • Signalment: Puppies and kittens

   • Histology: Multifocal necrosis with lymphoplasmacytic inflammation and protozoal tachyzoites

2. Neospora caninum

   • Signalment: Calves

3. Intermediate stages of tapeworm = Occasional eosinophilic myocarditis due to parasite degeneration

   • eg. Cysticercus ovis aka. sheep measles in the heart (no clinical significance)

Heart Base Tumours (2)

1. Aortic Body Chemodectoma = Neoplasm of the aortic body chemoreceptors

   1. Develop in the wall of the proximal aorta → Occlude the Ao → LCHF

   2. Signalment: Rare and only seen regularly in dogs

   3. Behaviour: Malignant, infiltrative neoplasms which do not metastasise

      • Poor prognosis

2. Neoplasms of Ectopic Thyroid Tissue

Structure of the Vascular System

• 3 Components

• 3 Layers (+ functions)

Components: Same 3 layers with variation in relative thickness of each layer

1. Arteries

2. Veins

3. Lymphatics

Layers:

1. Tunica Intima = Innermost layer of the vascular system continuous with the endocardium of the heart

   1. Consists of small amounts of fibrous tissue and lined by a single layer of endothelial cells which produce anti-coagulation factors

2. Tunica Media = Middle layer continuous with the myocardium

   1. Consists of concentric bands of smooth muscle which produce factors stimulating repair of surrounding cells

   2. Large artery = Smooth muscle contracts to propel blood
      Small arteries and veins = Smooth muscle maintains vascular tone and BP

3. Tunica Adventitia = Outer tough and fibrous layer which is continuous with the epicardium

   • Prevents vessel rupture

4 Types of arterial diseases (+ DDx)

1. Aneurysms and Ruptures (3)

2. Thrombosis and Embolism (3)

3. Degeneration and Necrosis of Arteries

   1. Arteriosclerosis (2)

   2. Atherosclerosis (3)

   3. Calcification (3)

   4. Fibrinoid necrosis (3)

4. Arteritis (4)

   1. Erysipelothrix of pigs

   2. Feline Infectious Peritonitis (FIP) of cats

   3. Malignant Catarrhal Fever (MCF) of cattle

   4. Strongylus vulgaris of horses

   5. Dirofilaria immitis of dogs

   6. Autoimmune vasculitis

Aneurysms (3)

• Definition

• 3 DDx

• Clinical signs

Definition: Focal outpouching of artery caused by reduced wall strength

DDx:

1. Strongylus vulgaris in horses (RARE)

2. Copper deficiency in pigs

   • Essential for normal elastin development

3. Idiopathic aortic aneurysm of male turkeys

Clinical Signs: NOT defected until rapid, fatal arterial rupture (± compression of surrounding organs)

What is this? (pig and horse heart)

• 3 DDx

• Location

• Clinical signs

Arterial Rupture (Ao)

DDx:

1. #1 trauma

2. Spontaneous or exercise-induced proximal Ao rupture of pigs and horses

   1. eg. Guttural pouch myosis in horses → Rupture of internal carotid artery → Rapid death

3. Arteritis caused by local inflammation or neoplasia

Location: Proximal Ao (within pericardial sac)

Clinical Signs: Rapid death due to haemopericardium → Cardiac tamponade

Most common cause of thrombosis in humans

Atherosclerotic plaques = Focal accumulation of fatty fibrous tissue within arterial elastic lamina → Loss of compliance

• NOT clinically significant in animals (except parrots with high fat diet → infarction)

• Seen in hypothyroid dogs but have no clinical signs associated (only important for diagnosis at PM)

Most common cause of thrombosis in animals and location

Atrial Thrombosis due to altered blood flow in atria caused by:

1. Alterations of heart shape (eg. cardiomyopathy)

2. Valvular damage → Regurgitant blood creating turbulence with the slow blood

3. Slowed blood flow due to CHF and compensatory atrial dilation

THREE outcomes of atrial thrombosis

1. Myocardial infarct (L)

2. Renal infarct (L)

3. Saddle thrombus (L)

What is this? (heart or parrot and Ao of cow)

• 2 Causes

• Location

• Clinical significance

Arterial Calcification (3)

Causes:

1. Cow = Debilitation (eg. Johne’s disease)

2. Hypercalcaemia (eg. cholecalciferol toxicity, CKD)

Significance: No effect (Ao #1 = Non-collapsible pipe)

Fibrinoid Arterial Necrosis (3)

• Definition

• 3 DDx

Definition: Necrosis of blood vessels resulting in oedema and haemorrhage within affected organs

DDx;

1. Pig and chicken vitE/Se deficiency

   • Pig:

     • Mulberry Heart Disease = Oedema and haemorrhage of the heart and pericardium

     • Hepatosis Dietetica = Haemorrhage of liver

   • Chicken: Oedema and haemorrhage in cerebellum and skeletal muscle

2. Oedema disease of pigs

3. Uraemia in dogs and cats = Fibrinoid necrosis of gastric and oral blood vessels

What is this?

• Signalment

• Pathogenesis

• Clinical sign

Erysipelothrix rhusiopathiae (4)

Signalment: Pigs and turkeys

• Zoonotic

Pathogenesis:

1. Infection → Septicaemia

2. Bacteria damage endothelium of the superficial blood vessels

3. Leads to thrombosis and multifocal cutaneous infarcts

4. Septicaemia also predisposes the pig to endocarditis and arthritis as there are lots of bacteria circulating the blood

Clinical Sign: Well-demarcated areas of reddening (“diamond skin disease”)

What is this? (cat peritoneal cavity, liver and brain)

• Agent

• Signalment

• Pathogenesis

• 5 Organ systems affected

• PM

• 2 Forms

• 6 Methods of diagnosis

  • Disadvantages

Feline Infectious Peritonitis (FIP)

Agent: Mutated feline enteric coronavirus (FCoV) = FIPV

• FCoV is ubiquitous in cat intestinal tracts but few develop mutated virus

Signalment: Purebred cat <2yr

Pathogenesis:

1. Cat infected with feline enteric coronavirus which colonises the intestinal tract

2. Virus mutates to FIPV in few cats which enables it to leave the intestines and circulate the blood within macrophages

   • Loses affinity for enterocytes and hence no longer infective

3. Circulating FIPV form Ab-Ag complexes which become trapped in smaller blood vessel

4. Inflammatory cells destroy immune complexes AND direct damage of virus → Vasculitis

5. Damaged blood vessels leak protein/fibrin-rich fluid into the body cavities and organs affected

6. Damaged blood vessels also result in thrombosis and infarction in various organs

Organs: Depends on which blood vessels are affected

1. Hepatic common → Multifocal infarcts

2. Renal common → Wedge-shaped infarcts

3. Intestinal

4. Mesenteric

5. Neurological (25% of cats only present with neurological signs)

PM: Variable with aggregates of fibrin and inflammation appearing as multiple white foci overlying the affected blood vessels = Leaked protein

Forms:

1. Dry/non-effusive = No peritoneal fluid and more difficult to diagnose

2. Wet/effusive = Damage to peritoneal blood vessels results in leakage of fluids into the peritoneal cavity and hence easier to diagnose

Diagnosis:

1. FCoV Ab Serology

   • -ve: Ubiquitous nature of disease makes it impossible to interpret a positive test result

2. Hyperglobulinaemia with Polyclonal Gammopathy of SPE

3. Peritoneal Effusion

   • Gross Appearance: Clear to slightly turbid, yellow which may clot due to high fibrinogen

   • Cytology: High protein and low cellularity (neutrophils and macrophages) with purple background

4. PCR of peritoneal fluid = #1

5. Rivalta Test = Drop of peritoneal fluid is placed into weak solution of acetic acid → Drop maintains shape if high protein

   • -ve: Only confirms high protein fluid (eg. exudate too)

6. Histology = Pyogranulomatous vasculitis #1

What is this? (cow)

• Agent

• Signalment

• Pathogenesis

• 5 Clinical signs

• Histology

Malignant Catarrhal Fever (MCF)

Agent: Ovine herpesvirus-2 (OHV-2)

Signalment: Cattle

• ALL sheep and most cattle infected asymptomatically

• FEW cattle develop MCF due to OHV-2 infection

Pathogenesis:

1. Cow becomes infected with OHV-2

2. Virus destroys subset of suppressor lymphocytes causing other lymphocytes to attack blood vessels

3. Results in generalised lymphocytic vasculitis

Clinical Signs: Variable depending on blood vessels affected

1. Ocular lesions = Corneal oedema, conjunctivitis and ulceration

2. GIT = Oral ulceration and diarrhoea

3. Nasal discharge

4. Coronary band ulceration

5. Change in temperament (more aggressive)

Histology: Lymphocytic arteritis (but no fibrin leakage as in FIP)

What is this? (horse)

Pathogenesis

Strongylus vulgaris

Pathogenesis:

1. Migration of larvae in blood vessels causes localised arteritis of the cranial mesenteric artery

2. Aneurysm → Rare rupture

3. Thrombosis → Terminal arterial embolism and intestinal infarction

4 DDx of autoimmune vasculitis

1. Beagle Pain Syndrome = Inflammation caused by auto-Ab against blood vessels in the meninges of the brain and spinal cord → Neck and back pain in dogs

2. SLE

3. Immune-mediated polyarteritis

4. Drug-induced hypersensitivity

What is this? (umbilicus)

Pathogenesis

Omphalophlebitis = Only venous inflammation (phlebitis) common in vet

Pathogenesis:

1. Neonate does not receive adequate colostrum which allows bacteria to infect the umbilical vein

2. Septic embolic develop from the umbilical vein which travel to the liver to cause hepatic abscesses

3. Bacteraemia with septic inflammation of the joints, meninges and kidneys

3 Lymphatic diseases and examples of each

1. Congenital malformation of lymphatics = Rare in dogs, cats and calves resulting in chronically swollen limb with marked pitting oedema

2. Bacterial lymphangitis (eg. Johne's Disease)

3. Damaged thoracic duct of cats → Chylothorax

Hamartoma (2)

Definition: Non-neoplastic developmental defect resulting in localised collection of normal-appearing blood vessels

Signalment: Most common in horses

Treatment: Spontaneous regression or curative surgical excision

Myocytes

• Structure

• 4 Organelles

• 3 Types

  • Metabolism

  • Appearance

  • Example muscle group

Structure: Long and narrow muscle cells which can be as long as the muscle itself (eg. LA myocytes are > 1m)

• Functional unit of the muscle → Many myocytes arranged in bundles (fascicle) which are separated by fibrous tissue

Organelles:

1. Sarcolemma = Cell membrane of the myocyte containing supporting cells (macrophages, satellite cells and fibroblasts)

2. Multiple peripheral nuclei throughout the length

3. Many mitochondria to generate significant energy required for contraction

4. Many myofibrils = Contractile unit/organelle of muscle which contain actin and myosin

   • Many myofibrils within ONE myocyte

Types:

1. Type I fibres (slow twitch cells)

   • Metabolism: Oxidative metabolism ONLY

   • Appearance: Red due to high vascularisation to supply muscles with O2 for slow and sustained contraction

   • Example: Bovine masseter muscle

2. Type IIa fibres (fast twitch cells)

   • Metabolism: Combination of oxidative and glycolytic metabolism

3. Type IIb fibres (fast twitch cells)

   • Metabolism: Glycolytic metabolism ONLY

   • Appearance: White (less vascularised) as designed to generate rapid, short movement

   • Example: Chicken pectoral muscles

Why are damaged myocytes observed in clusters on histology?

Muscle contains more than one type of fibre, and a disease process typically affects one type more severely than the other

Because myocytes are long, damage is usually?

Restricted to ONE part of the myocyte

THREE Responses of Muscle to Injury

• Cause

• Pathogenesis

ONE: Easy Repair and Complete Regeneration

Cause: Sarcolemma remains intact

Pathogenesis:

1. Macrophages from sarcolemma enter the cell to remove necrotic debris

2. Satellite cells enter the myocyte to produce replacement myofibrils which bridge the defect

3. After repair, satellite cells return to the sarcolemma

TWO: Complete Regeneration OR Fibrosis

Cause: Sarcolemma disrupted

Pathogenesis:

1. Sarcolemma disruption causes loss of macrophages and satellite cells

2. Each end of the myocyte bulges TWO possible outcomes

   1. If two ends make contact, sarcolemma is restored to heal myocyte by complete regeneration

   2. If the defect is too extensive, it is bridged by fibrous tissue → Loss of muscle strength and elasticity

THREE: Cell Death

Cause: Damage to ENTIRE cell

Pathogenesis:

• Cell death resulting in mineralisation

• Defect created by lost myocyte is filled with fibrous tissue

Interpreting colour change in muscle on PM

Necrosis: Pale as damaged myocytes swell which squeezes blood from the tissue

Caution:

1. Muscle with high proportion of type IIb fibres (eg. chicken pectoral muscle) is normally paler than muscles with high proportion of type I fibres (eg. bovine masseter muscle)

2. Rigor mortis results in areas of pallor due to skeletal muscle contraction BUT is typically less well-demarcated than true necrosis

Describe TWO ways to classify muscle injury (+ DDx)

1. Distribution

   1. Monofocal = Lesion at ONE site within the body and consistent with a local process (eg. trauma or injection site reaction)

   2. Multifocal = Lesions at MULTIPLE site within the body and consistent with a systemic process (eg. toxicity or VitE/Se deficiency)

2. Time

   1. Monophasic = Lesions that develop during a SINGLE damaging incident → Myocytes ALL at the same stage of degeneration and repair on histology (eg. single fatal toxin ingestion or capture myopathy)

   2. Multiphasic = Lesions caused by REPEATED episodes of muscle damage → Myocytes at different stages of degeneration on histology as cell die at different times (eg. muscular dystrophy, vitE/Se deficiency, canine polymyositis)

      • eg. Normal, recent death = swollen, invaded by macrophages and satellite cells, mineralisation, fibrosis

FIVE Types of changes in muscle size

As myocytes cannot divide, changes in muscle size are limited to atrophy or hypertrophy (no hyperplasia)

1. Denervation atrophy (4)

2. Disuse atrophy (3)

3. Atrophy due to cachexia (3)

4. Physiological hypertrophy (4)

5. Pathological hypertrophy (4)

What is this? (horse larynx)

• Definition

• Pathogenesis

Denervation Atrophy (4) = Laryngeal hemiplegia (horse and dog)

Definition: Denervation of a significant proportion of myocytes → Rapid and marked decrease in myocyte size (vs. disuse atrophy)

• Usually entire muscle atrophies as it is supplied by ONE nerve

Pathogenesis: Long-nerve degeneration

1. Progressive degeneration of the left recurrent laryngeal nerve (longest nerve in body)

2. Denervation of left intrinsic muscles of the larynx

3. Laryngeal hemiplegia and marked atrophy of the LEFT dorsal cricoarytenoid muscle

4. Vocal folds collapse resulting in roaring during exercise

Pathogenesis and characteristics of disuse atrophy (3)

Muscle immobilisation (eg. casting) → Less severe and longer period of atrophy development (vs. denervation atrophy)

• Readily reversible and rarely clinically significant

Atrophy due to Cachexia (3)

• Pathogenesis

• Muscles LEAST affected

Pathogenesis:

1. Marked malnutrition/neoplasia → Cachexia

2. Muscle protein catabolism and atrophy

Least Affected: Postural muscles

Muscle Hypertrophy (4)

• Pathogenesis

• 2 Types

Pathogenesis: Addition of myofibrils within the myocyte

• Extreme = Additional intracellular fibrous tissue → splitting of myocyte

Types:

1. Physiological Hypertrophy = Normal reaction of muscle to increased workload (eg. racehorses in training)

2. Pathological Hypertrophy = Increased muscle mass due to disease process resulting in increased workload of remaining cells (eg. hypertrophy of contralateral limbs or remaining myocytes within the muscle)

List FOUR biochemistry/urinalysis changes associated with skeletal disease

1. Creatine kinase (CK)

2. Aspartate aminotransferase (AST)

3. Myoglobinuria/myoglobinaemia

4. Hyperkalaemia

Creatine Kinase (CK) vs. Aspartate Aminotransferase (AST)

• Advantages

• Disadvantages

Creatine Kinase (CK)

+ve: Specific for skeletal and cardiac muscle

-ve:

1. Artefactual increase in haemolysed samples or hyperbilirubinaemia

2. Short half-life (~4hr) → Monophasic muscle necrosis results in return of CK to normal within 24 - 48hr

Aspartate Aminotransferase (AST)

+ve: Longer half-life than CK (measure in conjunction with CK to assess severity and progression of muscle disease ± prognosis)

-ve: NOT specific for muscle (released by liver and muscle cell damage

Pathogenesis of Mb leakage with muscle necrosis

Feature of SEVERE and active muscle necrosis/degeneration

1. Mb released from damaged and necrotic muscle cells (myoglobinaemia = brown serum)

2. Mb readily filtered by renal glomeruli into urine due to low molecular weight and lack of serum binding (myoglobinuria = brown urine)

3. Mb is toxic to renal tubular cells resulting in acute renal failure (myoglobinuric nephrosis)

Pathogenesis of hyperkalaemia caused by muscle necrosis

Hyperkalaemia may occur in severe, necrotising muscle disease due to widespread release of intracellular K+ and exacerbated by acute renal failure caused by myoglobinuric nephrosis

Muscle Diseases

• 4 Congenital/genetic DDx

• 3 Environmental/physical DDx

• 5 Infectious DDx

• 3 Immune-mediated DDx

• 3 Nutritional/Toxicity DDx

Congenital/Genetic DDx:

1. Congenital muscular hypertrophy (4)

2. Splayleg in pigs and swimmer puppies (3)

3. Malignant hyperthermia (3)

4. Storage diseases (3)

Environmental/Physical DDx:

1. Exertional rhabdomyolysis (5)

2. Capture myopathy (3)

3. Trauma (5)

Infectious DDx:

1. Blackleg (4)

2. Gas gangrene (3)

3. Woody tongue (4)

4. Cysticercosis (3)

5. Sarcocystosis (4)

Immune-Mediated DDx:

1. Polymyositis (3)

2. Masticatory muscle myositis (3)

3. Extraocular myositis

Nutritional/Toxicity DDx:

1. VitE/Se deficiency (4)

2. Iron deficiency

3. Monensin toxicity (3)

Myotonia (1)

Definition: Group of rare inherited diseases causing sustained involuntary contraction of a muscle group

Signalment: Young (6 - 12w) horses, dogs and cats OR goats

Subtypes:

1. Necrotising Subtype (horses, dogs and cats)

   • Pathogenesis:

     1. Often caused by dysfunctional membrane ion channels

     2. Allows sustained muscle contraction

     3. INITIAL: Results in muscle swelling due to hypertrophy and foci of muscle necrosis

     4. LATER: Continue muscle necrosis → Visible muscle atrophy and fibrosis

     5. Clinical Signs: Stiff gait, remarkable exercise intolerance, swelling → atrophied muscles

     6. Histology: Mild - moderate multifocal and multiphasic necrosis and regeneration

2. Benign Subtype (goats)

   • Clinical Sign: Sudden collapse in response to voluntary effort (eg. due to stress) "Fainting goats"

   • Significance: NONE!

Congenital Muscular Hypertrophy (4)

• Signalment

• Pathogenesis

Signalment: Calves (eg. Double-muscle and Belgian Blue) = Selected trait

Pathogenesis:

1. Developmental defect in myostatin = Protein that inhibits muscle growth

2. Results in increased muscle size due to myocyte swelling and reduced IM adipose (≤ 60%)

3. No impaired function BUT issues with dystocia common

Steatosis (2)

Signalment: Incidental condition identified in slaughtered cattle

Pathogenesis: Improper development of myocytes results in replacement with adipose tissue

Histology: Increased adipose separating the myocytes

• Difficult to differentiate from chronic myocyte necrosis

Muscular Dystrophy (1)

Definition: Group of rare genetic defects that develop within cytoskeletal proteins of the myocytes

• eg. Duchenne-type muscular dystrophy #1 due to dystrophin defect which is encoded for by the largest gene in the body

Histology: Multifocal and multiplastic muscle necrosis

Signalment: Rarely seen in several dog breeds (Labrador) and DSH

• ONLY males as x-linked

Pathogenesis:

1. Congenital defect in dystrophin = protein which anchors the myofibrils to the cell membrane

2. Results in excessive movement between the cell membrane and internal parts of the cell each time the muscle contracts

3. Causes cell damage, progressive necrosis and fibrosis of myocytes within muscles throughout the body

Clinical Signs:

1. Stiff gait and exercise intolerance by 10w

2. Muscles initially large due to swelling caused by necrosis → Marked muscle atrophy due to loss of myocytes

3. Aspiration pneumonia due to dysphagia

4. Death due to heart failure (disease affects cardiac myocytes too)

Splayleg in Pigs and Swimmer puppies

• Pathogenesis

• Clinical sign

• Prognosis

Pathogenesis: Weakened adductor muscles (congenital predisposition?)

Clinical Sign: Animal is unable to place legs under their bodies

Prognosis: Spontaneous recovery as the animal ages

What is this? (pig muscle)

• Pathogenesis

• Signalment

• Clinical sign

• PM

• Diagnosis

Malignant Hyperthermia (3) aka. Porcine stress syndrome

Signalment: Pig and human

Pathogenesis:

1. Genetic defect in ryanodine receptor results in loss of normal excitation-contraction coupling

2. Disease triggered by stress or exposure to halothane anaesthetic

3. Large influx of Ca2+ into the myocyte

4. Results in sustained muscle contraction

5. Excessive heat and intracellular lactic acid is produced resulting in myocyte necrosis

6. Death due to hyperthermia or acidosis

PM: Muscles of back, shoulder and thigh are swollen, pale and "cooked"

Histology: Multifocal and monophasic muscle necrosis

Diagnosis: Genetic testing (well-defined)

Storage Disease (3)

• Definition

• Signalment

• Pathogenesis

• Histology

• Diagnosis

Definition: Variety of storage diseases develop due to a variety of inherited enzyme deficiencies

• eg. Polysaccharide storage myopathy of horses #1

Signalment: Up to 50% of horses have varying severity of this disease

• Draft-type horses #1 as bred for more CHO = increased work duration

Pathogenesis:

1. Increased CHO within myocytes allows muscles to contract for longer without rest

2. Results in excess heat and lactic acid production

3. Increased susceptibility to exertional rhabdomyolysis

4. Advanced cases of recurrent exertional rhabdomyolysis results in muscle atrophy and weakness due to necrosis

Histology: Multifocal and multiphasic muscle necrosis

• Consistent with exertional rhabdomyolysis with large quantities of CHO within intact myocytes

Diagnosis: Biopsy

What is this? (horse muscle and kidney)

• Signalment

• Pathogenesis

• 2 Risk factors

• 3 Clinical signs

• PM

• Prevention

Exertional Rhabdomyolysis (5) aka. Tying up, Monday morning disease, sit-fast, azoturia

Signalment: Horse (± greyhound and sled dog)

Pathogenesis:

1. Horse accumulates high levels of IM glycogen

2. Allows oxidation of excessive glycogen in myocytes

3. Results in excessive production of heat and lactic acid

4. Because there is no alarm mechanism in horse muscle to detect excessive heat and lactic acid → Continuous oxidation of glycogen

5. Results in muscle necrosis and increased serum CK

Risks:

1. Horse with PSSM

2. Horses fed high-quality feed and irregularly exercised

Clinical Signs:

1. Stiffness, pain and swelling of muscles immediately after exercise (esp. gluteal and lumbar muscles as used most during exercise)

2. ± Myoglobinaemia (brown serum)

3. ± Myoglobinuric nephrosis (brown urine and AKI)

PM:

1. Pale and swollen muscles

2. Dark brown kidneys

Prevention: Feed lower quality feed or exercise more regularly

What is this? (deer)

• Signalment

• Pathogenesis

• PM

Capture Myopathy (3)

Signalment: Wild deer #1

Pathogenesis:

1. Capture, chase or transport results in sustained adrenaline release

2. Adrenaline results in continuous supply of glycogen to the muscle enabling sustained contraction (vs. exertional rhabdomyolysis which has pre-existing excess glycogen in muscle)

3. Sustain contraction allows accumulation of lactic acid and heat in the muscle

4. Results in myocyte necrosis with TWO outcomes Outcomes

   1. Immediate death due to metabolic acidosis

   2. Survival of acidosis → AKI due to myoglobinaemia

PM:

1. Swollen, pale thigh and back muscles

2. ± Ruptured thigh muscles

3. ± Mb-stained kidneys with survival of acidosis

4. ± Multifocal muscle calcification with survival of acidosis

Downer Cow (5)

• Pathogenesis

• Diagnosis/Prognosis

Pathogenesis:

1. Cow goes down due to 1˚ disease (eg. hypocalcaemia or hypomagneaemia)

2. Weight of animal on trapped limb occludes blood flow resulting in hypoxia and muscle necrosis

3. Necrotic muscle swelling resulting in further hypoxia and necrosis

4. Resultant muscle damage may prevent cow from standing even after 1˚ problem is resolved

Diagnosis/Prognosis: Predictive scale developed to predict which cattle suffered extensive muscle damage and unlikely to ever stand again

1. Muscle enzymes (AST)

2. Number of days recumbent

3. Urea

   • Downer cows have reduced renal perfusion due to dehydration

2 Exotic viral diseases causing muscle disease

1. Blue-tongue (orbivirus)

2. Foot and Mouth Virus (picornavirus)

2 reasons why bacterial colonisation of muscle is RARE (even with severe bacteraemia)

1. Myocytes wrapped in tough cytoskeleton that is hard for bacteria to infiltrate

2. Muscle normally has rich blood supply = Lots of O2 and neutrophils

What is this? (cow muscle)

• Agent

• Signalment

• Pathogenesis

• PM

• Histology

• Diagnosis

Blackleg

Agent: Clostridium chauvoei

Signalment: Cattle ONLY

• ~1yr coming through gates OR bulling injuries

Pathogenesis: Acute necrotising myositis

1. Clostridium chauvoei spores ingested with pasture and enter the bloodstream to travel to the skeletal muscle

2. Spores lie dormant within skeletal muscle as they cannot germinate in healthy, highly oxygenated skeletal muscle

3. Traumatic injury results in muscle hypoxia enabling bacterial germination

4. Bacteria produce toxins causing vasoconstriction

5. Vasoconstriction results in ischaemia and necrosis of surrounding tissue which allows local extension of infection (ample new hypoxic substrate)

6. Vasoconstriction also prevents neutrophils from reaching bacteria (no resolution of infection and impossible to treat with antibiotics)

7. Rapid death within 24hr due to endotoxaemia (release of bacterial toxins and toxic metabolites of necrotic tissue)

PM:

1. Black discolouration of muscle due to venous pooling

2. Emphysematous muscle due to bacterial gas production = Gas bubbles which is palpable as crepitus under the skin

3. Characteristic rancid butter smell from gas produced by bacteria

4. Advanced autolysis due to high fever antemortem

Histology: Monofocal and monophasic necrosis

• No neutrophils (vasoconstrictive toxins)

• Clear spaces between myocytes (gas)

• ± Large G+ bacilli

Diagnosis: History of no vaccination AND histology for definitive diagnosis

• Culture is NOT useful (dead animal → germination of spores)

What is this? (arrow = penetrating wound)

• Signalment

• Agent

• Pathogenesis

• PM

Gas Gangrene aka. Malignant Oedema

Signalment: Herbivores more susceptible than carnivores

• Big head = Ram head butting → Gas gangrene of head

Agent: Clostridium septicum/perfringens/chauvoei/novyi

Pathogenesis:

1. Deep penetrating wounds become infected with clostridium spores from the environment

2. Wounds form an anaerobic environment via hypoxia

3. Critical determinant of disease occurrence depends on speed which the body mounts the immune reaction

   • Slow immune response → Bacterial proliferation and vasoconstrictive toxins production

   • Swift immune response → Macrophages and neutrophils kill bacteria before they multiply and produce toxins

4. Same pathogenesis as blackleg from here

PM: Affected areas range from light-coloured with massive oedema and emphysema to dark and haemorrhagic

Trichinella (1)

Agent: Trichinella spiralis

Prevalence: Reduced prevalence in NZ pigs due to extensive meat inspection and improved management practices

Pathogenesis:

1. Pig becomes infected by eating skeletal muscle containing encysted Trichinella spiralis larvae

2. Larvae develop into adults and produce larvae which encyst within skeletal muscle where they are protected from the immune system

Clinical Sign: Muscle pain

Histology: Curled up larvae visible within swollen, glassy myocytes (nurse cells) surrounded by mild fibrosis and minimal lymphoplasmacytic inflammation

• Occasional cyst degeneration → Exposed larvae → Stimulates acute eosinophilic or pyogranulomatous inflammatory response

Cysticercosis (3)

• Agent

• Signalment

• PM

• Histology

Agent: Cysticercus ovis

Signalment: Sheep and goats = IH (dog = DH)

Pathogenesis:

1. Sheep become infected with Cysticercus ovis from Taenia ovis eggs secreted by dogs in faces

2. Cysts develop in the heart and skeletal muscle of sheep and goats (sheep measles)

3. Dog becomes infected by ingesting encysted larvae in unfrozen/uncooked sheep meat

PM: Numerous small, white foci within skeletal muscle

Histology: Tapeworm larvae surrounded by mild fibrosis and small numbers of inflammatory cells

Sarcocystosis (4)

• Agent

• Lifecycle

• Pathogenicity

Agent: Protozoa (requires TWO hosts to complete lifecycle)

Lifecycle:

1. Protozoan eaten by IH and enters bloodstream

2. After much asexual reproduction, protozoa enter skeletal muscle

3. DH infected by eating contaminated muscle

Pathogenicity: Asymptomatic unless IH ingests lots of protozoan which simultaneously invade myocytes

• Hypersensitivity reaction to encysted protozoa → Eosinophilic myositis

Neosporosis (1)

Agent: Neospora caninum

• Abortion in cattle

• Neuritis and myositis in dogs

Signalment: Puppies and immunocompromised dogs

Clinical Signs: Progressive weakness of HL or rigidity

Prognosis: Poor in advanced cases

What is this?

• Signalment

• Pathogenesis

• Clinical signs

• Serum biochemistry

• Histology

Polymyositis (3)

Signalment: Dog #1

Pathogenesis:

1. Body produces auto-Ab against muscle Ag

2. Results in necrosis and inflammation

Clinical Signs: Periodic flares

1. Muscle pain and swelling

2. Generalised atrophy and weakness due to fibrosis (± limb contracture)

Biochemistry: Chronic mild - moderate elevation in CK/AST

Histology: Multifocal and multiphasic myocyte necrosis

• Regeneration and fibrosis with neutrophilic or lymphoplasmacytic inflammation

What is this?

• Signalment

• Pathogenesis

• Histology

• Treatment

Masticatory Muscle Myositis (3) aka. Eosinophilic myositis and Atrophic myositis

Signalment: Vizsla dogs

Pathogenesis:

1. Body produces auto-Ab against type II masticatory myosin (unique to temporalis and masseter muscles)

2. INITIAL: Necrosis and eosinophilic myositis → Swelling and pain while eating

3. LATER: Myocytes replaced by fibrosis resulting in atrophy

4. Dog starves to death as they cannot open mouths wide enough to et

Histology:

• ACUTE: Multiphasic myocyte necrosis with inflammation ± lots of eosinophils

• CHRONIC: Loss of myocytes and replacement fibrosis

Treatment: Prompt treatment during acute muscle swelling to prevent irreversible replacement of myocytes by fibrosis