PATHOLOGY OF THE CARDIOVASCULAR SYSTEM Shannon Martinson, 2018 VPM 2220 – Systemic Pathology II http://people.upei.ca/smartinson/ Lecture 4 - Myocardium
PATHOLOGY OF THE CARDIOVASCULAR SYSTEM
Shannon Martinson, 2018 VPM 2220 – Systemic Pathology II
http://people.upei.ca/smartinson/
Lecture 4 - Myocardium
• The myocardium has striations (sarcomeres)
• Myocardial fibres are branched and join each other
through the intercalated disks
• The cardiomyocytes contain abundant mitochondria
and myoglobin
MYOCARDIUM
Normal structure
Sarcomere
Z Z
Myofilaments
Nucleus
Sarcolemma Sarcoplasm
Unlike skeletal muscle, the myocardium has little/no capacity to replace lost myofibers, therefore normal repair is impossible
MYOCARDIUM
Normal structure
• Cardiomyocytes are susceptible to damage from hypoxia, free radicals, viruses, bacteria, toxins, etc • Microscopically, degeneration and necrosis are similar to that in skeletal muscle
Normal Myocardium: Striation and myofilaments have an
orderly arrangement in the sarcoplasm
Myocardial degeneration: Loss of striations, hypereosinophilia,
swelling, dissolution of sarcoplasm and myofibrils, and nuclear condensation.
MYOCARDIUM – NECROSIS
Degeneration and Necrosis
• Cardiomyocytes are susceptible to damage from hypoxia, free radicals, viruses, bacteria, toxins, etc • Microscopically, degeneration and necrosis are similar to that in skeletal muscle
Normal Myocardium: Striation and myofilaments are orderly
arranged in sarcoplasm
Myocardial degeneration: Loss of striations, hypereosinophilia,
swelling, dissolution of sarcoplasm and myofibrils, and nuclear condensation.
MYOCARDIUM – NECROSIS
Degeneration and Necrosis
• Calcium plays an important role in normal cardiac physiology • In many degenerative diseases this mineral is sequestered in the sarcoplasm / organelles of
the cardiomyocytes • Causes myocardial calcification or mineralization
Ca++
Ca++
MYOCARDIUM – NECROSIS
Cell Necrosis and Calcification
Ca++
Ca++
MYOCARDIUM – NECROSIS
Cell Necrosis and Calcification Excessive calcium deposits appear microscopically as a dark-blue granules in the sarcoplasm
Gross: Pale white foci in the myocardium
MYOCARDIUM – NECROSIS
Myocardial Necrosis and Repair • Necrosis elicits a leukocytic
response • Macrophages and neutrophils
infiltrate and start phagocytizing necrotic debris
Images: Dr. C. Legge
MYOCARDIUM – NECROSIS
Myocardial Necrosis and Repair • Cardiac muscle has almost no
capacity to repair • Necrotic tissue is replaced by
connective tissue (fibroblasts) • Results in myocardial fibrosis
(scarring)
Gross: Pale white foci in the myocardium
MYOCARDIUM – NECROSIS
Ischemic Myocardial Necrosis
• Myocardial infarcts • Very common in
humans: • Atherosclerosis
→Heart attack • Rare in animals
Cardiomyocyte necrosis can be : • Ischemic • Toxic • Nutritional • Neurogenic
MYOCARDIUM – NECROSIS
Toxic Myocardial Necrosis
Myocardial degeneration and necrosis in left ventricle • Monensin toxicity in a horse
Examples of cardiotoxins: • Ionophores • Antineoplastic meds
• Cyclophosphamide • Doxorubicin
• Doxycycline • Toxic plants
• Gossypol • White snakeroot • Nerium oleander • Cassia occidentalis
• Cantharidin (blister beetle)
Noah’s arkive
• Affects farm animals
• Often manifests as sudden death
• Occurs mostly in rapidly growing animals
• Exacerbated by exercise or stress
• Can affect fetuses and cause abortion
• For unknown reasons, sometime WMD affects only skeletal muscle, or cardiac muscle, and sometimes both
• Responds well to treatment, but only at the early stages of the disease
MYOCARDIUM – NECROSIS
Nutritional Myopathy White Muscle Disease
MYOCARDIUM – NECROSIS
Nutritional Myopathy White Muscle Disease
Selenium and Vitamin E deficiency
Decreased scavenging of free radicals
Peroxidation of cell membranes
Cardiac and skeletal muscle necrosis and mineralization
Free radicals are produced during normal cardiac metabolism
Pathogenesis
White Muscle Disease
MYOCARDIUM – NECROSIS
Nutritional Myopathy
• 2 day old calf – failure to thrive since birth • Sudden collapse – brought to AVC • Irregular heart rhythm • Marked ↑CK and AST • Marked hyperkalemia, hypochloremia, hyponatremia
White Muscle Disease
MYOCARDIUM – NECROSIS
Nutritional Myopathy
• 2 day old calf – failure to thrive since birth • Sudden collapse – brought to AVC • Irregular heart rhythm • Marked ↑CK and AST • Marked hyperkalemia, hypochloremia, hyponatremia
Myocardial Degeneration and Calcification
• Often affects the LV in calves
White Muscle Disease
MYOCARDIUM – NECROSIS
Nutritional Myopathy
• Often affects the right ventricle in lambs
• Submit samples from the LV and RV for histology
White Muscle Disease
MYOCARDIUM – NECROSIS
Nutritional Myopathy
Von-Kossa stain for Calcium
Pheochromocytoma in a dog
• Brain trauma can cause myocardial necrosis • Possibly due to release of catecholamines
• Catecholamine release from a pheochromocytoma causes the same lesions
Brain Heart Syndrome
MYOCARDIUM – NECROSIS
Neurogenic myocardial necrosis
Myocarditis rarely occurs alone, it is typically part of a systemic disease
MYOCARDIUM
Myocarditis
Suppurative Lymphocytic
Eosinophilic Hemorrhagic
Granulomatous
• Canine parvovirus causes enteritis
• Can also cause myocarditis in newborn pups
MYOCARDIUM
Myocarditis Parvoviral myocarditis
Pathology of Domestic Animals, Elsevier, 2016 Pathologic Basis of Veterinary Disease. Elsevier 2012
Canine Parvovirus (CPV-2)
• Histophilus somni may cause
• Thrombotic Meningo-Encephalitis (TME)
• Bronchopneumonia
• Myocarditis – feedlots especially
• Arthritis
• Reproductive problems
MYOCARDIUM
Myocarditis Histophilosis
Histophilus somni
MYOCARDIUM
Myocarditis Histophilosis • Causes vasculitis with infarction of the myocardium • Often involves the papillary muscles • Can also cause multifocal abscesses Histophilus somni
Can cause acute death
or chronic progressive
heart failure.
• Trueperella pyogenes can cause infection and inflammation in many organs
• In some cases blood dissemination leads to heart abscesses or endocarditis
MYOCARDIUM
Myocarditis Myocardial Abscesses
Trueperella pyogenes
• Staphylococcus aureus often causes systemic infections in lambs and kids
• One of the lesions is myocarditis which progresses from acute to chronic to
organized myocardial abscesses
MYOCARDIUM
Myocarditis Tick pyemia Staphylococcus aureus
FMVZ-UNAM
Indirect cycle
Cysticercus Taenia
Gross appearance of cysticerci: • Fluid filled cysts
containing white larvae
MYOCARDIUM
Myocarditis Cysticercosis Taenia spp
Cardiomyopathy refers to a myocardial abnormality that results in changes in cardiac wall thickness, causes electrical disturbances and often results in sudden unexpected death
• Genetic or idiopathic (suspected genetic) in origin • Mutations in genes coding for contractile proteins,
cytoskeletal proteins, mitochondrial enzymes • In animals, most are idiopathic
MYOCARDIUM - CARDIOMYOPATHY
Courtesy of Amanda Kelly
Mostly affect dogs and cats
Four main forms of Cardiomyopathy 1. Hypertrophic
Cardiomyopathy (HCM) 2. Dilated Cardiomyopathy
(DCM) 3. Restrictive Cardiomyopathy
(RCM) 4. Arrhythmogenic Right
Ventricular Cardiomyopathy (ARVC)
• So called “Secondary cardiomyopathies” • Non-genetic in origin
• Hyperthyroidism in cats • Concentric ventricular hypertrophy
• Taurine deficiency in cats • Eccentric biventricular hypertrophy
• Must also rule out anomalies such as congenital shunts, valvular disease and hypertension
MYOCARDIUM - CARDIOMYOPATHY
Cardiomyopathy refers to a myocardial abnormality that results in changes in cardiac wall thickness, causes electrical disturbances and often results in sudden unexpected death
• Most common form of feline cardiomyopathy • Clinical signs include: lethargy, discomfort / hiding,
dyspnea, tachypnea, acute paralysis of the hindlimbs; or no overt signs but detection of murmur
• Occasionally causes sudden death • Anesthetic death
Hypertrophic Cardiomyopathy
MYOCARDIUM - CARDIOMYOPATHY
Gross finding: • ↑ Heart mass • Concentric hypertrophy • Symmetric or Asymmetric
• LV • IVS • +/- RV
• Left atrial dilation
• Most common form of heart disease in the cat
• Affects males more than females (2:1) • Maine Coon and Ragdoll cats
• Inherited defects in cardiac myosin binding protein gene
Hypertrophic Cardiomyopathy
MYOCARDIUM - CARDIOMYOPATHY
HCM is characterized by: • Stiff fibers • Impaired ability to accept diastolic flow from
the left atrium • Relatively normal systole until the end-stage
Gross finding: • Less common:
• Ventricular fibrosis
10-20% caudal aortic thrombi
Hypertrophic Cardiomyopathy
MYOCARDIUM - CARDIOMYOPATHY
Pathology of Domestic Animals, Elsevier, 2016
• Cats with saddle thrombi may present with pain, hind end paresis, cold hind limbs and weak or absent femoral pulses (uni or bilateral)
Gross finding: • Less common:
• Atrial thrombosis
Hypertrophic Cardiomyopathy
MYOCARDIUM - CARDIOMYOPATHY
Normal myocardium HCM: Cardiomyocyte hypertrophy and disarray
Histology
• Most common form of canine cardiomyopathy • Most common in large breed dogs
• Clinical signs include: dyspnea, depression, weight loss, syncope, murmur, arrhythmia, abdominal distension
• Occasionally - sudden death with no preceeding signs
MYOCARDIUM - CARDIOMYOPATHY
Dilated Cardiomyopathy
Gross finding: • Increased heart mass • Biventricular and atrial dilation
(eccentric hypertrophy) • Thin flabby walls • Attenuated papillary muscles
MYOCARDIUM - CARDIOMYOPATHY
Dilated Cardiomyopathy • Eccentric hypertrophy resembling DCM occurs in cats and farmed foxes - secondary to a dietary taurine deficiency
DCM is characterized by: • Progressive cardiac dilation • Decreased contractile force • Systolic dysfunction
Histology: • Subtle changes
• Wavy attenuation of cardiomyocytes • Degeneration and fibrosis
Restrictive Cardiomyopathy
MYOCARDIUM - CARDIOMYOPATHY
• Primarily in cats • Often used as a functional term rather than disease
entity • Diagnosed based on echocardiography • Characterized by left ventricular stiffness and
impaired diastolic function • Ventricular thickness is typically normal • Systolic function is usually normal • One (left) or both atria are enlarged
• Murmurs and dysrhythmias are common Pathology texts often include endocardial fibroelastosis of Burmese cats and excessive
moderator bands in the RCM category
• Left congestive heart failure often occurs • Few cats survive for more than 1 year after diagnosis
Restrictive Cardiomyopathy
MYOCARDIUM - CARDIOMYOPATHY
• Gross findings • LV fibrosis
• Endocardial • Myocardial
• Atrial enlargement • +/- Mural thrombi
Left ventricular endocardial fibrosis
• Some cases may represent end-stage HCM or infarction from HCM
• Some cases may be preceded by endomyocarditis
From: Kimura Y et al. Pathological Features and Pathogenesis of the Endomyocardial Form of Restrictive Cardiomyopathy in CatsJ CompPath 2016, Vol 155
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
MYOCARDIUM - CARDIOMYOPATHY
• Primarily in Boxer dogs • Striatin gene mutation
• Less often in other dog breeds and in cats
• May see • Ventricular arrhythmias • Syncope • Heart failure • Sudden death
• Gross findings • +/- Dilation of the right ventricle
• Histology: • Replacement of RV (+/- LV) cardiomyocytes by
adipose or fibroadipose tissue
From EM Oxford et al. Heart Rhythm. 2007 September ; 4(9): 1196–1205.
Excessive LV moderator bands
( = False tendons)
Congenital endocardial fibroelastosis
Other primary myocardial abnormalities
MYOCARDIUM - CARDIOMYOPATHY
Excessive moderator bands
• CT Bands span between the IVS and LV free wall
• Minimal heart enlargement • Incidental or a rare cause of LHF
Excessive LV moderator bands
( = False tendons)
Congenital endocardial fibroelastosis
MYOCARDIUM - CARDIOMYOPATHY
www.studyblue.com/notes/note/n/cardiomyopathy-and-heart-failure/deck/3232147
Endocardial fibroelastosis
• Hereditary disease in Burmese cats • Diffuse endocardial fibrosis • LV eccentric hypertrophy • Histology: Abnormal deposits of
collagen and elastic fibres in the endocardium
http://www.photomazza.com/?Felidae
Sincere thanks to Drs A Lopez and E Aburto, AVC, for their contribution to this material.