cardiovascular 4 Flashcards
describe the following results from a left to right shunt: bounding pulse, continuous murmur, mitral valve leak
Bounding pulse - Increase in systolic and decrease in diastolic resulting in increased pulse pressure
- Increase systolic pressure - ejection of blood from the heart - stroke volume increased as increase end diastolic volume (more blood going around lungs back into left atrium and ventricle)
- Decrease diastolic pressure - blood volume and arteriolar resistance - blood volume is decreased as leakage of blood into the PDA - loss of pressure
Continuous murmur - cannot hear S1 and S2 heart sounds - generally caused by PDA
Mitral valve leak - compensatory method for increased volume is eccentric hypertrophy resulting in stretched heart which can pull apart the mitral valve causing incompetence
What are the consequences of a patent ductus arteriosus
1) left to right shunt - more blood being pumped around pulmonary circulation
2) eccentric hypertrophy of left ventricle due to increase in volume
3) can result in increase resistance in pulmonary system - cor pulmonale due to remodelling of the vessels
4) changes the shunt to right to left
5) differential cyanosis - PDA after brachiocephalic and left subclavian therefore they are getting oxygenated blood (cranial body) while caudal body gets mixture of oxgenated and deoxygenated blood as bypassing the lungs
What are the 4 clinical signs of right to left shunt
1) Red mucus membrane - differential cyanosis results in increase red blood cell production resulting in increased PCV and therefore more intense red in cranial mucus membranes
2) Blue mucus membrane in caudal areas - differential cyanosis results in deoxygenated blood within the caudal area
3) Weakness hind-limbs - differential cyanosis results in deoxygenated blood in the caudal area
4) Seizures - differential cyanosis results in increase red blood cell production (explained above) resulting in increased viscosity of the blood and therefore decrease flow within the brain as increase resistance - resulting in hypoxic damage to areas of the brain - seizures
what are the 2 treatment options for right to left shunts and what wouldn’t you do
Cannot undergo surgery as permanent remodelling of the pulmonary vessels has already occurred and therefore closing the PDA will only increase the resistance in the pulmonary system which will lead to right sided congestive heart failure
1) Chemotherapeutic drugs to suppress red blood cell production
- Body is responding to hypoxia from low circulating blood volume by increasing red blood cell production resulting in increased viscosity which in turn leads to seizures therefore to reduce seizures decrease red blood cells
2) Blood letting
- Need to be careful about how much blood you take out of the animal as taking out red blood cells that are already deoxygenated
- Remove blood to decrease blood volume - this will activate RAAS which increases water retention and therefore helps counteract the increase in red blood cells - reducing the viscosity and therefore decreasing the seizures
What are the possible adverse effects of myocardial degeneration, necrosis, inflammation or neoplasia on cardiac function
- if animals survive the initial phase the damaged areas will undergo reparative fibrosis
- neoplasm - intra-pericardial haemorrhage (with risk of cardiac tamponade), impairment of chamber filling or emptying, valvular insufficiency, intra-cardiac thrombosis and hence thromboembolism, and/or metastasis to other sites
what is the common cause of arrhythmia/dysrhythmia
secondary to myocardial damage rather than to primary lesions of the cardiac conduction system
- - injuried myocadrium may depolarise repeatedly independent on conduction tissue
What are potnetial causes of hydropic or fatty degeneration of cardiac myofibres
hydropic - problems with Na+/K+ pump - hypoxia
fatty degeneration - hepatic insufficiency - increase fatty acids in the blood
What is brown atrophy of the heart, In which species is it most commonly seen and when
- atrophy is often accompanied by gross dark brown discolouration of the myocardium (“brown atrophy”) due to severe intra-cellular accumulation of golden-brown lipofuscin pigment (“wear-and- tear pigment”) caused by cumulative peroxidative injury to phospholipids of cell and organelle membranes
- high-producing dairy cows, particularly Ayrshire cows (in which there may be a genetic predisposition
What are the two main forms of tissue mineralisation and for each describe a cause
Dystrophic mineralisation
- white muscle disease (due to vitamin E or selenium deficiency
Metastatic minearlisation -
may be prominent grossly in such conditions as vitamin D toxicity and vitamin D analogue poisoning
when is the capacity of mitotic division of cardiac myofribres lost
decreases in late foetal life and is lost in the early neonatal period
Where are foci of myocardial necrosis most likely to be found in the heart and why
left ventricle, especially in the subendocardial myocardium of the interventricular septum and in the papillary muscles (these are the sites of greatest chamber wall tension development during systole)
How long must a patient survive after necrosis of cardiac myofibres before the lesions are likely to become grossly obvious and what gross lesions might you see
4-12 hours post-injury when subtle pallor may emerge
18-24 hours - necrotic zone is pale maybe dystrophic mineralisation
2-4 days - necrotic foci become more prominent due to reactive hyperaemia with neutrophil and macrophages
7 days - fibroplasia
list 4 causes of mycardial necrosis and what do they attack
1) ischaemia/hypoxia - shock
2) excess catecholamines - overdose of synpathomimetric drugs
3) nutritional deficiencies - vitamin E/selenium deficiency - white muscle disease
4) drugs and chemical toxins - fluoroactetate 1080
Attack cardiac and skeletal myofibres
how long can cardiac myofibres tolerate hypoxic conditions and why common in humans
20-30 minutes of hypoxia - necrosis of cardiac myofibres
consequence of atherosclerosis of the coronary arteries with thrombosis +/- thromboembolism
List 3 causes of myocardial ischaemic/hypoxic injury
1) thrombosis/thromboembolism of coronary arterial branches
2) aged animals - lumina of coronary arteries and arterioles may decrease because of arteriosclerosis/arteriolosclerosis
3) dilated and hypertrophied hearts
What are the circumstances in domestic animals in which β-adrenergic stimulation of the myocardium can result in myocardial necrosis
overdose with negative inotropic drugs (e.g. β-adrenergic blockers such as propanolol
List 4 plants that contain toxins capable of causing myocardial necrosis and what species most likely to be intoxicated
1) Avocado leaves - horses, birds
2) phalaris - sheep
3) fluoroacetate containing plants - ruminants
4) canola oil
What is the aetiopathogenesis of white muscle disease (nutritional myopathy) and which
animals are most likely to be affected?
Most likely effect domestic ruminants such as lambs and calves
- highly unpredictable occurrence, with triggering factors including rapid growth in juvenile animals, unaccustomed exercise, cold weather, dietary factors (e.g. high intake of unsaturated fatty acids from pasture plants), iron injections that increase demand for anti-oxidants etc
what gross lesions would you expect to find in a lamb or beef calf that has died from white muscle disease
mineralisation on major skeletal muscles of the shoulder, myocardium (right ventricle lambs, left ventricle calves)
What is the aetiopathogenesis of mulberry heart disease in young pigs
excellent nutritional condition at 2-4 months of age
- sudden death is due to acute right- and/or left-sided congestive heart failure +/- ventricular arrhythmia
What cardiac lesions might you expect to find in a pig that has died from mulberry heart
disease
multifocal to diffuse haemorrhage in the epicardium, myocardium and subendocardium and patchy myocardial pallor due to multifocal necrosis
usually only minor dystrophic mineralisation of the affected myocardium
List 4 large groups of causes of myocarditis and examples within
1) viruses - canine parvovirus
2) protozoa - toxoplasma gondii
3) helminths - nematodes
4) bacteria - clostridium
How do you reach a diagnosis of
cardiomyopathy
Always by exclusion of other possible causes - further down the diagnosis steps
what are the gross characteristics of hypertrophic cardiomyopathy what common in and what effect on function
- cardiomegaly with prominent concentric hypertrophy of the LV and IV septum
- common in cats
- myocardial contractility is usually increased or normal but diastolic filling of the ventricles is decreased (i.e. diastolic failure)
What are the 3 major forms of cardiomyopathy
1) hypertrophic cardiomyopathy
2) dilated cardiomyopathy
3) restrictive cardiomyopathy
what are the gross characteristics of dilated cardiomyopathy, what major effect does it have on cardiac function and which species most common in
- heart appears flabby and the chambers thin-walled
- characterised by decreased myocardial contractility, increased end-diastolic volume of the ventricles and decreased ventricular ejection (i.e. systolic failure)
- common in dogs
what was previously an important cause for cardiomypoathy in cats
causal association with taurine deficiency was recognised in the late 1980s and the taurine content of commercial diets was increased accordingly
what effect does restrictive cardiomyopathy have on cardiac function, which species common
- stiffness, reduced ventricular compliance and impaired diastolic filling of especially the LV
- myocardial contractility is usually normal
- mainly seen in middle-aged or older cats
what is a common consequence of cardiomyopathy in cats and what clinical signs would alert you to this
intra-cardiac thrombosis and thromboembolism
- typically see sudden onset of bilateral or unilateral hindlimb paresis, with absence of femoral pulses, cool hindlimbs, cyanotic nail beds and firm painful hindlimb muscles
- the ischaemic hindlimb muscles undergo dry gangrene
what neoplasm can involve the heart in dogs, what is the most common form and where does it arise and how behave
metastases from malignancies arising elsewhere but some may be primary
haemangiosarcoma
- arises as a red-black haemorrhagic mass subepicardially in the wall of the right atrium or at the entrance to the right auricle
○ tends to metastasise widely, often as “cannonball” metastases to the lungs
what is the tumour that commonly involve heart in ruminants
Peripheral nerve sheath tumour
List some differentials for gross appearance of small cream-white foci randomly scattered in the heart
1) dystrophic or metastatic minearlisation - white muscle disease
2) fluid fluid parasitic cysts
3) multifocal myocarditis from bacteia, virus, parasite
4) causes of myocardial necrosis such as ischaemia/hypoxia, plant toxins
what 4 sympathetic compensatory effects of heart failure and negatives
1) vasoconstriction - increase TRP and maintain BP but increase afterload
2) increase HR and SV so increase in CO but increase work
3) renal effects - increase BP by retention of H2O and Na - increase preload
increased TRP to maintain BP - increase afterload
4) cardiac hypertrophy to increase SV - increase work of contraction
What occurs with chronic activation of sympathetic nervous system
1) Reduced baroreceptor sensitivity–> maintained sympathetic drive even when MAP is appropriate
2) Down regulation of beta receptors in the heart–> reduced capacity of heart to respond to sympathetic stimulation
Chronic activation of RAAS
• Persistent vasoconstriction –> increased pre load and afterload
• Increased blood volume–> increased preload
• Increased angiotensin–> decreased baroreceptor sensitivity myocardial toxicity
What are the 3 downsides of cardiac hypertrophy
1) Decreased capillary and mitochondrial density –> decreased energy supply
2) Decreased inotropy and lusitropy
- decreased inotropy–> “weak” heart (systolic heart failure)
- decreased lusitropy–> “stiff” heart (diastolic heart failure)
3) Increased risk of arrythmias
- Poor supply of oxygen to cardiac myocytes
What are the 5 main groups of drugs to treat heart failure
1) positive inotropes
2) negative inotropes
3) diuretics
4) vasodilators
5) antiarrythmics
what do positive ionotropes do, how problematic and list the 4 classes
- increases cardiac contractility by increasing intracellular calcium - increase workload on heart - may be bad
1) Cardiac glycosides
2) B adrenoceptor agonists (mimic adrenalin and noradrenalin)
3) Phosphodiesterase inhibitors
4) Calcium sensitisers
Cardiac glycosides what class of drug, example and mechanism of action
positive iontropes - digoxin
- Inhibit Na/K ATPase pump
- Increased intracellular Na
- Decreased Na movement into cell
- Decreased exchange of calcium out of cell - increase intracellular concentration - increase contractility
explain the effects Cardiac glycosides have on the heart
positive iontrope
- Direct effect on the myocardium:
○ Shortened refractory period in atria & ventricles
- Vagal effects on pacemaker tissues:
○ Slowed AV conduction
○ Vagal effect on SA and AV nodes (slowing of HR) - increase vagal tone
- Decreased sympathetic drive- mediated from medullary cardiovascular centre
Explain the possible toxic effects of cardiac glycosides
Low therapeutic index (TI = max non toxic dose/minimum effective dose • Na/K ATPase pumps are everywhere! - Myocardial effects--> arrhythmias - G-I signs - CNS signs - Ototoxicity • Hypokalaemia exacerbates toxicities… Digoxin competes with K+ for the Na/K ATPase pump so decrease retention of K+ in kidneys - hypokalaemia - also occurs with diuretics so could be an issue if use together
Beta adrenoreceptor agonists what type of drug in heart failure, effects, adverse effects and examples
positive inotropes
- use in severe acute heart failure
- increase HR
adverse effects - arrhythmias, increase work load on heart
1) dobutamine - beta 1 specific
2) adrenaline - beta 1 and 2 - trachycardia
Phosphodiesterase inhibitors what type of drug in heart failure and effects
positive inotrope Inhibition of phosphodiesterase - Less b’down of cAMP - Higher cAMP--> - Increased Ca influx --> - Increased cardiac contractility
Calcium sensitisers what type of drug in heart failure, example, effect and how does it work
Pimobendan
• Similar mechanism to other PDE inhibitors ( increased Ca (intracellular) through increased cAMP)
- potent vasodilatory - reduce pre and afterload
- don’t know how it works
negative inotropes how work and the 2 classes
- To reduce the work load on a failing heart
1) Beta adrenergic antagonists
2) Calcium channel blockers
Beta antagonists what type of drug in heart failure, effect and side effects
negative inotropes
Decreased cardiotoxic effects of excessive sympathetic drive - improving beta receptor expression
• Decreased activation of RAAS so decreased afterload and preload
- decreased HR and contractility
- Increased ‘window’ for coronary perfusion
Side effects
- Some animals relying on sympathetic drive to survive in this state and therefore may push animal into decompensatory heart failure so need to consider whether have the proper reserve
- Broncho constriction in asthmatics (more humans)
- Hypoglycaemia in diabetics
- Bradycardia and heart block
- Fatigue
- Cold extremities
- Heart failure at higher doses
what type of vessels are most vunreable to compression, occlusion, neoplastic invasion by extension of inflammation from adjacent tissues
veins and lymphatics due to narrower walls than arteries and arterioles
how is the inner and outer half of the wall of a blood vessel suppplied with oxygen
- vasa vasorum supply the tunica adventitia and outer half of the tunica media
- the tunica intima and inner half of the tunica media are avascular and rely on oxygen and nutrient diffusion from the vessel lumen
How do vascular smooth muscle cells respond to sustained increase in blood volume or pressure
by undergoing hypertrophy and, to a lesser extent, hyperplasia
what causes hypertrophy of the smooth muscle cells of arterioles and what are possible consequences
- sustained hypertension (increased blood pressure) or hyperperfusion (increase blood flow)
- consequence is further hypertension as lumen decreases - increasing resistance to flow
what circumstances does sustained arteriolar vasoconstriction occur and what is the possible consequence
1) sustained vasoconstrction in cold climates - frost bite
2) mycotoxins
consequence - sustained arteriolar vasoconstriction - exacerbation of the hypertension (due to increased vascular resistance) +/- downstream ischaemic tissue injury
What does arteriosclerosis look like grossly, what is the clinical significance and is it common
- may not be grossly obvious, slightly raised, thickened, wrinkled intima
- rarely clinical significance
- common in older domestic animals
what are the characteristic lesions of atherosclerosis, when is it likely to develop and what is the clinical significance
1) atheroma (fibrofatty plaque) - core of lipid covered by fibrous cap
2) fatty streak - soft, smooth, lipid-rich
- myocardial infarction, and ischaemic injury in peripheral tissues
- generally not clinically significant
list 5 circumstances in which fiibrinoid change develop in domestic animals
1) renal failure
2) system hypertension
3) vasculitis
4) selenium/vitamin E deficiency
5) oedema disease in pigs
in what disease states is arterial mineralisation occur
areas of vasculitis, arteriosclerosis, atherosclerosis or thrombosis
Apart from trauma, what are potential causes of arterial rupture in domestic animals
- spontaneous rupture pf uterine artery, internal carotid artery, aorta - tears in ascending aorta, pulmonary artery (less common)
What are the potential consequences of vasculitis
- depend on the size, number and type of vessels involved, the degree of associated thrombosis, haemorrhage and oedema, presence of collateral circulation etc
- vessel wall damage
what is the usual cause of lymphoedema and what is the difference between primary and secondary lymphoedema
Primary - results from anomalous development of lymphatic system inadequate formation of lymphatic channels
secondary - obstruction of previously normal efferent lymphatics
what are the two main tumors arising from vascular endothelium in domestic animals
1) Haemangioma - benign tumor - blood filled spaces
2) haemangiosarcoma - malignant neoplasm, older dogs and german shepherds common
Antiarrythmics what is important to remember and how
remember to treat the patient – not the arrhythmia
1) Direct damage to the heart-
- eg chamber enlargement, cardiomyopathy, myocarditis, myocardial ischaemia
2) Systemic abnormalities
- Eg electrolyte or acid-base imbalances , toxicity – drugs,uraemia, septicaemia, pyometra, hypoxia, fever, endocrine disorders e.g. hyperthyroidism, autonomic activity- pain, gastric dilatation/ volvulus
what are some clinical signs of arrhythmias and mechanism
1) Lack of substrate delivery due to inadequate cardiac output
- exercise intolerance
- weakness, syncopal episodes
- chest pain/ angina : difficult to document in animals
2) Electrical instability
- syncope, sudden death - ventricular fibrillation
3) Refractory or worsening heart failure
- sudden development of dysarrythmia (e.g. atrial fibrillation or ventricular tachycardia) may lead to decompensation of previous stable congestive signs
How to diagnose arrhythmias
ECG
-normal heart rate, regular rhythm, P wave for every QRS
what are the 5 classes/drugs of antiarhymtic drugs
1) Sodium channel blockers
2) Beta blockers
3) Potassium (outward) channel blockers
4) Calcium channel blockers
5) Other drugs eg digoxin
Sodium channel blockers what type of drug mechanism of action, special characteristic and therefore when most useful
Mechanism of Action:
- block movement of Na+ which myocytes need to contract however pacemaker cells do not
Use dependence - more active sodium channels have a greater likelihood of being blocked herefore more excitable ( eg ectopic) cells are more likely to be blocked
Rogue pacemaker cells that are spontaneously depolarising - sodium channel blockers can stop this by allowing SA node to reset
sodium channel blockers side effects
1) can promote arrhythmia
2) wrong dose can have effect on nervous tissue
beta blockers effects
- Inhibit sympathetic stimulation to heart
- Control dysrhythmias driven by excessive sympathetic tone
- Used in atrial tachycardias
- Slow sinus (SA) rate - effect the pacemaker cells - driven by SA node
○ Slow AV conduction
beta blockers uses and example
- Use in patient that is dependent on sympathetic drive can be lethal - decompensate patient and push into heart failure
- Used in humans to treat stress induced tachycardia
- Used in dogs to treat fear related behaviours - behavioural specialist
• Examples: propranolol
calcium channel blockers what used for with heart. mechanism of action, when used
arrythmias
L-‐Type Calcium Channel Blockers
- Bind to Calcium channel from inside - Use dependence again
- Render channel inactive
- Cells dependent on these channels for depolarisation are more likely to be affected ie NODAL tissues
- Useful in atrial tachycardias- ventricular tachycardias are not responsive
Calcium channel blockers effects and the selectivity
Effects
- Nodal /conducting tissue–> decreased heart rate, & AV conduction (pacemaker tissue)
- Myocardium –> decreased force of contraction
- Vascular smooth muscle –> relaxation
Vascular: myocardial selectivity:
- Verapamil 1:1 therefore more use in arrhythmia
- Diltiazem 7:1 some vascular effects
- Amlodipine 14:1 vascular ( antihypertensive)
Digoxin what is the mechanism to help with ventricular arrhythmias
- Vagal effects on pacemaker tissues:
- Slowed AV conduction - increase risk of rogue pacemaker establishing itself
- direct effect on myocardial NA/K ATPase
Atrial fribrillation and ventricular tachycardia what drugs to use
Atrial 1) digoxin, beta blocker, calcium channel blocker 2) Na channel blocker Ventricular 1) sodium channel blocker
what are the following general effects of negative iontropes, positive inotropes, diuretics, vasodilators, antiarrhythmics
Positive inotropes increase cardiac contractility, cardiac output
Negative inotropes decrease cardiac contractility, decrease preload
Diuretics decrease preload (volume overload)
Vasodilators decrease preload, afterload or both
Antiarrhythmics increase cardiac output
what are the consequences of Mitral Valve Endocardiosis
○ Resulting in left atrial enlargement
○ Results in atrial fibrillation - no obvious P waves, irregular R-R intervals,
○ Also resulting in left-sided cardiac failure resulting in pulmonary oedema
why is there an increase in fractional shortening in mitral valve endocardiosis
1) Responding reduced ejection fraction, reduced cardiac out - sympathetic nervous system activation - increase contractility
2) Responding to stretch of the ventricle, increase distance between myofibrils resulting in optimal length-tension relationship
Mitral valve endocardiosis list the initial treatment
Restore oxygen supply decrease pulmonary oedema
1) Diuretics - Frusemide - given intravenously until oedema resolves once resolves decrease dose to prevent side effects of acid-base abnormalities, dehydration and electrolyte imbalance
2) Provide an oxygen enriched atmosphere and reduce oxygen demand with rest
Reduce preload
1) Diuretics - Frusemide - reduce blood volume to reduce venous return which reduces
2) Pimobendan - peripheral vasodilating to reduce preload (also increases contractility
What treatment would you provide after the ascites so once right sided heart failure has developed with mitral valve endocardiosis
1) Spironolactone - add a potassium sparing diuretic as frusemide can decrease potassium which can have an effect on the side effects of digoxin
2) Digoxin - depleted potassium greater effect as digoxin competes with K+ for the active site on the Na+/K+ ATPase and therefore depletion in K+ will result in increased effects of digoxin
Mechanism for the development of ascites secondary to congestive heart failure
Stretch of the heart due to increase end diastolic volume resulting from the regurgitation of the mitral valve - pulling apart of the tricuspid valve resulting in tricuspid valve incompetence - increase regurgitation into right atrium - congestion into cranial and caudal vena cava - increase hydrostatic pressure in abdomen - net filtration in venous end of capillary - ASCITES
What are the 4 classes of Diuretics and example of each
1) Proximal Convulted Tubule - carbonic anhydrase inhibitor
2) loop diuretics - Frusemide
3) Distal Convoluted Tubule - Thiazides
4) collecting duct - spironolactone
Proximal convoluted tubule mechanism of action
Carbonic Anhydrase Inhibitor
- Prevents formation of H+ and therefore prevent H+ being exchanged for Na+ at the apical membrane
○ Increase loss of bicarbonate in urine
○ Increase loss of Na+ and water
Loop Diuretics mechanism of action and possible problems
Frusemide
- Inhibits Na/K/2Cl cotransporter
- Most powerful diuretics
- May cause
○ Hypokalaemia as K+ is secreted into tubular lumen via channel and reabsorbed via the cotransporter that is inhibit by this diuretic
Potentiate toxicity of cardiac glycosides
Distal convoluted tubule diuretics mechanism of action and what may cause
Thiazides
- Inhibit Na/Cl luminal cotransporter so drop Na+ and Cl- levels
- Also cause potassium loss due to increased flow rate through collecting duct
○ Hypokalaemia
○ Hypoantraemia - low Na+ blood levels
collecting duct diuretic mechanism of action
- Potassium sparing diuretics
1. Spironolactone: synthetic aldosterone inhibitor - Decreased luminal Na+ channels
- Decreased Na/K/ATPase on basal membrane - increase loss of Na+ and decreases loss of K+
