PATHOLOGY OF THE CARDIOVASCULAR SYSTEM

Transcription

1 PATHOLOGY OF THE CARDIOVASCULAR SYSTEM Lecture 4 - Myocardium Shannon Martinson, 2018 VPM 2220 Systemic Pathology II

2 Normal structure 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

3 Normal structure MYOCARDIUM Unlike skeletal muscle, the myocardium has little/no capacity to replace lost myofibers, therefore normal repair is impossible Sarcolemma Sarcoplasm Nucleus Z Z Sarcomere Myofilaments

4 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 have an orderly arrangement in the sarcoplasm Myocardial degeneration: Loss of striations, hypereosinophilia, swelling, dissolution of sarcoplasm and myofibrils, and nuclear condensation.

5 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.

6 MYOCARDIUM NECROSIS Cell Necrosis and Calcification 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++ Ca++ Ca++

7 MYOCARDIUM NECROSIS Cell Necrosis and Calcification Excessive calcium deposits appear microscopically as a darkblue granules in the sarcoplasm Gross: Pale white foci in the myocardium

8 MYOCARDIUM NECROSIS Myocardial Necrosis and Repair Necrosis elicits a leukocytic response Macrophages and neutrophils infiltrate and start phagocytizing necrotic debris

9 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) Images: Dr. C. Legge Gross: Pale white foci in the myocardium

10 MYOCARDIUM NECROSIS Ischemic Myocardial Necrosis Cardiomyocyte necrosis can be : Ischemic Toxic Nutritional Neurogenic Myocardial infarcts Very common in humans: Atherosclerosis Heart attack Rare in animals

11 MYOCARDIUM NECROSIS Toxic Myocardial Necrosis Examples of cardiotoxins: Ionophores Antineoplastic meds Cyclophosphamide Doxorubicin Doxycycline Toxic plants Gossypol White snakeroot Nerium oleander Cassia occidentalis Cantharidin (blister beetle) Myocardial degeneration and necrosis in left ventricle Monensin toxicity in a horse Noah s arkive

12 MYOCARDIUM NECROSIS Nutritional Myopathy White Muscle Disease 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

13 Nutritional Myopathy MYOCARDIUM NECROSIS Pathogenesis White Muscle Disease Selenium and Vitamin E deficiency Free radicals are produced during normal cardiac metabolism Decreased scavenging of free radicals Peroxidation of cell membranes Cardiac and skeletal muscle necrosis and mineralization

14 Nutritional Myopathy MYOCARDIUM NECROSIS White Muscle Disease 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

15 Nutritional Myopathy MYOCARDIUM NECROSIS White Muscle Disease Myocardial Degeneration and Calcification 2 day old calf failure to thrive since birth Sudden collapse brought to AVC Irregular heart rhythm Marked CK and AST Often affects Marked hyperkalemia, hypochloremia, hyponatremia the LV in calves

16 Nutritional Myopathy MYOCARDIUM NECROSIS White Muscle Disease Often affects the right ventricle in lambs Submit samples from the LV and RV for histology

17 Nutritional Myopathy MYOCARDIUM NECROSIS White Muscle Disease Von-Kossa stain for Calcium

18 Neurogenic myocardial necrosis MYOCARDIUM NECROSIS Brain Heart Syndrome Brain trauma can cause myocardial necrosis Possibly due to release of catecholamines Catecholamine release from a pheochromocytoma causes the same lesions Pheochromocytoma in a dog

19 MYOCARDIUM Myocarditis Myocarditis rarely occurs alone, it is typically part of a systemic disease Suppurative Lymphocytic Eosinophilic Hemorrhagic Granulomatous

20 Myocarditis MYOCARDIUM Canine Parvovirus (CPV-2) Parvoviral myocarditis Pathologic Basis of Veterinary Disease. Elsevier 2012 Pathology of Domestic Animals, Elsevier, 2016 Canine parvovirus causes enteritis Can also cause myocarditis in newborn pups

21 Myocarditis MYOCARDIUM Histophilosis Histophilus somni Histophilus somni may cause Thrombotic Meningo-Encephalitis (TME) Bronchopneumonia Myocarditis feedlots especially Arthritis Reproductive problems

22 Myocarditis MYOCARDIUM Causes vasculitis with infarction of the myocardium Often involves the papillary muscles Can also cause multifocal abscesses Can cause acute death or chronic progressive heart failure. Histophilosis Histophilus somni

23 Myocarditis MYOCARDIUM Myocardial Abscesses Trueperella pyogenes Trueperella pyogenes can cause infection and inflammation in many organs In some cases blood dissemination leads to heart abscesses or endocarditis

24 Myocarditis MYOCARDIUM Staphylococcus aureus Tick pyemia 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

25 Myocarditis MYOCARDIUM Taenia spp Cysticercosis Taenia Indirect cycle Cysticercus Gross appearance of cysticerci: Fluid filled cysts containing white larvae FMVZ-UNAM

26 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 Mostly affect dogs and cats Genetic or idiopathic (suspected genetic) in origin Mutations in genes coding for contractile proteins, cytoskeletal proteins, mitochondrial enzymes In animals, most are idiopathic Courtesy of Amanda Kelly Four main forms of Cardiomyopathy 1. Hypertrophic Cardiomyopathy (HCM) 2. Dilated Cardiomyopathy (DCM) 3. Restrictive Cardiomyopathy (RCM) 4. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

27 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 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

28 MYOCARDIUM - CARDIOMYOPATHY Hypertrophic Cardiomyopathy 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 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

29 MYOCARDIUM - CARDIOMYOPATHY Hypertrophic Cardiomyopathy Gross finding: Less common: Ventricular fibrosis HCM is characterized by: Stiff fibers Impaired ability to accept diastolic flow from the left atrium Relatively normal systole until the end-stage

30 MYOCARDIUM - CARDIOMYOPATHY Hypertrophic Cardiomyopathy 10-20% caudal aortic thrombi 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 Pathology of Domestic Animals, Elsevier, 2016

31 MYOCARDIUM - CARDIOMYOPATHY Hypertrophic Cardiomyopathy Histology Normal myocardium HCM: Cardiomyocyte hypertrophy and disarray

32 MYOCARDIUM - CARDIOMYOPATHY Dilated Cardiomyopathy 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 Gross finding: Increased heart mass Biventricular and atrial dilation (eccentric hypertrophy) Thin flabby walls Attenuated papillary muscles

33 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

34 MYOCARDIUM - CARDIOMYOPATHY Restrictive 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 Left congestive heart failure often occurs Few cats survive for more than 1 year after diagnosis Burmese cats and excessive moderator bands in the RCM category

35 MYOCARDIUM - CARDIOMYOPATHY Restrictive 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

36 MYOCARDIUM - CARDIOMYOPATHY From EM Oxford et al. Heart Rhythm September ; 4(9): Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) 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

37 MYOCARDIUM - CARDIOMYOPATHY Other primary myocardial abnormalities Excessive moderator bands Excessive LV moderator bands ( = False tendons) Congenital endocardial fibroelastosis CT Bands span between the IVS and LV free wall Minimal heart enlargement Incidental or a rare cause of LHF

38 MYOCARDIUM - CARDIOMYOPATHY Endocardial fibroelastosis Excessive LV moderator bands ( = False tendons) Congenital endocardial fibroelastosis Hereditary disease in Burmese cats Diffuse endocardial fibrosis LV eccentric hypertrophy Histology: Abnormal deposits of collagen and elastic fibres in the endocardium

39 Sincere thanks to Drs A Lopez and E Aburto, AVC, for their contribution to this material.