Theme 9: Cardiovascular Pathology I & II Flashcards
What is the definition of ischaemic heart disease?
generic designation for a group of syndromes resulting from myocardial ischaemia
What is myocardial ischaemia?
an imbalance between demand and supply of oxygenated blood to the heart
What is by far the most common cause of ischaemic heart disease?
coronary artery thrombosis
Other than coronary artery thrombosis, what is another cause of ischaemic heart disease?
hypertrophy of cardiac muscle (increases demand and leads to imbalance)
What are the 4 IHD syndromes?
- Myocardial infarction –> Long duration and severe ischaemia causes myocardial death
- Angina pectoris –> ischaemia is less severe and doesn’t cause myocardial death
- Chronic IHD with heart failure
- Sudden cardiac death
How does angina present?
classic central chest pain
what are the 3 types of angina pectoris?
- stable angina - chest pain aggrevated by exercise or increased demand
- prinzmetal angina - due to vasospasms and usually associated with stress
- Unstable angina - cardiac chest pain initiated independant of exertion
Why does chronic IHD cause heart failure?
atherosclerotic changes that narrow the coronary arteries resulting in a longer duration, less severe ischaemia resulting in decreased contractility of cardiac myocytes, resulting in heart failure
Which 3 syndromes make up acute coronary syndrome?
- Myocardial infarction
- Unstable angina
- Sudden cardiac death
What is the biggest killer of both men and women in the UK?
Ischaemic heart disease
What are the risk factors for IHD?
- High BP
- lipid profile abnormalities
- diabetes
- not total cholesterol but HDL and TC:HDL ratio
- smoking
- sedentary lifestyle
Explain the pathogenesis of MI
Myocardial ischaemia is a consequence of reduced blood flow in the coronary arteries in the heart due too:
- fixed vessel narrowing
- abnormal vascular tone as a result of atherosclerosis
- endothelial dysfunction
This leads to an imbalance between myocardial oxygen supply and demand
What is the definition of a myocardial infarction?
- death of cardiac muscle from prolonged ischaemia
- can be transmural or subendocardial
Where does an MI usually begin? Why?
- in the subendocardium
- this is the least perfused area of the ventricular wall
- this then leads to transmural infarction
What is an atheromatous plaque made up of?
- Fibrous cap - smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization
- Necrotic center - cell debris, cholerstol crystals, foam cells, calcium
- Media
What are the steps leading to an MI?
- Acute plaque changes
- Platelet aggregration
- Thrombus formation
- Occlusion of coronary artery
Explain the appaearance of the myocardium at the start of infarction, up to 6 weeks later
<24 hrs: normal
1-2 days: pale, oedema, myocyte necrosis, neutrophils
3-4 days: yellow with haemorrhagic edge, myocyte necrosis, macrophages
1-3 week: pale, thin, granulation tissue then fibrosis
3-6 week: dense fibrous scar
What are the complications of an MI?
- arrhythmias (either directly or by limited perfusion to the conduction system e.g SA node –> will occur suddenly)
- congestive heart failure
- thromboembolism
- pericarditis
- ventricular aneurysm
- cardiac tamponade (haemopericardium)
- cardiogenic shock
What are the blood markers of IHD?
- Troponins T&I
- raised post MI, pulmonary embolism, heart failure and myocarditis - Creatine kinase
- Myoglobin
- Lactate dehydrogenase isoenzyme 1
- Aspartate transaminase
What is the definition of hypertension?
a sustained diastolic pressure greater than 90 mmHg or sustained systolic pressure greater than 140 mmHg
What are the causes of primary hypertension?
multifactorial:
- genetic - insulin resistance (metabolic syndrome)
- environmental (obesity, alcohol, smoking, stress, Na+ intake)
How do we calculate blood pressure?
BP = cardiac output x peripheral resistance
both these variables are affected by many factors
Explain how the Renin-angiotensin-aldosterone system works
- drop in blood pressure/ fluid volume
- renin released from kidney
- renin converts angiotensinogen (in liver) into angiotensin I
- ACE converts angiotensin I to angiotensin II
- Angiotensin II acts on the adrenal gland to stimulate the release of aldosterone
- Aldosterone acts on the kidneys to stimulate reabsorption of salt and water
- Angiotensin II acts directly on blood vessels, stimulating vasoconstriction
What are the functions of angiotensin II?
- Constricts resistance vessels thereby increasing systemic vascular resistance and arterial pressure
- Stimulates sodium transport (reabsorption) at several renal tubular sites, thereby increasing sodium and water retention by the body
- Acts on the adrenal cortex to release aldosterone, which in turn acts on the kidneys to increase sodium and fluid retention
- Stimulates the release of vasopressin (ADH) from the posterior pituitary, which increases fluid retention by the kidneys
- Stimulates thirst centres within the brain
- Facilitates norepinephrine release from sympathetic nerve endings and inhibits norepinephrine re-uptake by nerve endings, thereby enhancing sympathetic adrenergic function
- Stimulates cardiac hypertrophy and vascular hypertrophy
what are some causes of secondary hypertension?
- Endocrine - cushing syndrome, acromegaly, thyroid disease
- Adrenal - conn’s disease, pheochromocytoma
- Renal - diabetic nephropathy, renal vascular disease, chronic glomerulonephritis
- CVS - aortic coarctation, renal artery stenosis
- Drugs - NSAIDs, oral contraceptives, steroids
What is malignant hypertension?
Bp > 180/120
- clinical signs and symptoms of organ damage develop
- acute hypertensive encephalopathy
- and/or nephropathy
What is hypertensive heart disease?
systemic (left sided) –> hypertrophy of the heart is an adaptive response to pressure overload that can lead to myocardial dilation, congestive heart failure and sudden death
What is the criteria for hypertensive heart disease?
left ventricular concentric hypertrophy and history or pathological evidence for hypertension
What is Cor Pulmonary?
- pulmonary (right sided) hypertensive heart disease
- right ventricular hypertrophy, dilation and potential heart failure secondary to hypertension caused by disorders of the lung or pulmonary vasculature
What are the causes of cor pulmonale?
- Diseases of the pulmonary parenchyma - COPD, cystic fibrosis, bronchiectasis
- Diseases of pulmonary vessels - thromboembolism, arteritis, drugs
- Disorders affecting chest movement - kyphoscoliosis
- Disorders inducing pulmonary arterial compression
What is Pickwikian syndrome
obesity related hypoventilation syndrome
- prevents normal chest movement
- can lead to cor pulmonale
What is an aneurysm?
a localised abnormal dilation of a blood vessel or the wall of a heart
What are the two types of aneurysm?
- True aneurysm - when dilated section is bounded by arterial wall components or the attenuated wall of the heart
- False aneurysm (pseudoaneurysm) - a breach in the vascular wall leading to an extravascular haematoma that communicates freely with the intravascular space
What is an arterial dissection?
- arises when blood enters the wall of an artery, as an haematoma dissecting between its layers
- dissections may, but do not always, arise in aneurysmal arteries
What are the two types of shapes of true aneurysms?
saccular - unilateral
fusiform - bilateral
What are the causes of aneurysms?
- atherosclerosis
- cystic medial degeneration (accompanies marfan syndrome)
- trauma
- congenital defects
- infections (mycotic aneurysms)
What is the most common cause of an abdominal aortic aneurysm?
atherosclerosis
How does an aortic dissection present?
with ‘knife-life’/ piercing chest pain
What is a hypertensive emergency
high BP with potentially life-threatening symptoms and signs indicative of acute impairment of one or more organ systems (brain, eyes, heart, aorta, or kidneys).
What is the most common cause of LVH?
Essential hypertension
What factors can cause heart failure?
- coronary artery disease
- hypertension
- cardiomyopathy
- arrhythmias
- valvulardisease
- congenital heart disease
- anamia
- thyroid disease
- alcohol
What is congestive heart failure?
- occurs insidiously or suddenly
- cumulative effects of chronic workload (hypertension and valve diseases) –> insidious
- acute haemodynamic stress (fluid overlodad and large myocardial infarction) - sudden
Explain the pathogenesis of left sided heart failure
- Hypertension/ valvular disease or myocardial infarction cause pressure and/or volume overload
- Increase cardiac work
- Increase wall stress
- Cell stretch and enhanced contractility
- Hypertrophy and/or dilation
What is the Frank Sterling Law of the Heart?
“As the ventricular volume increases and stretches the myocardial muscle fibres, the stroke volume increases up to its maximum capacity. This allows the cardiac output to be synchronised with the venous return, the arterial blood supply and the wall length without depending on external regulation”
How can the heart compensate for cardiac disfunction?
- Activation of renin-angiotensin-aldosterone system
2. Release of norepinephrine
What are the clinical effects of left sided failure due to?
- low cardiac output and hypoperfusion of tissues
- pulmonary congestion
What are the signs and symptoms of left sided heart failure?
- orthopnea
- dyspnoea
- PND (paroxysmal nocturnal dyspnoea)
- blood tinged sputum
- cyanosis
- pulmonary hypertesion
What are the effects of reduced kidney perfusion? (as a result of low cardiac output)
- Pre-renal azotemia
- abnormally high levels of nitrogen containing compounds on the blood can lead to AKI and increased serum creatinine - renin-angiotensin-aldosterone activation
- effect of RAAS is to increase salt and fluid retention
What are the causes of right sided heart failure?
- left sided heart failure (causes back up blood in left side of heart so blood becomes backed up in lungs)
- cor pulmonale
What are the signs and symptoms of right sided heart failure?
systemic and portal venous system engorgement –> portal hypertension, fluid accumulation
- congestive splenomegaly
- ascites
- odema
- plural and pericardial effusions
- transudates
What is stenosis?
- failure of valves to open completely, impeding flow
- leads to pressure overload
what is regurgitation or incompetence?
- failure of valves to close completely allowing reverse flow
- leads to volume overload
What is the cause of aortic stenosis in over 70s?
senile calcification of anatomically normal aortic valve
What is the cause of aortic stenosis in over 50-70s?
Calcification of a deformed (congenitally bicuspid aortic valve)
What are the 3 consequences of aortic stenosis?
- LVH
- ischaemia
- cardiac decompensation
- angina
- CHF
what causes mitral stenosis?
rheumatic fever
How can an infection with group A streptococcus result in heart failure?
- can lead to rheumatic fever
- can damage heart valves (now rare in UK due to antibiotics)
What are the acute signs of mitral stenosis?
- inflammation
- aschoff bodies
- anitschknow cells
- pancarditis (inflammation of the entire heart)
- vegetations can form on chordae tendinae at leaflet junction
What are the chronic signs of mitral stenosis?
- thickened valves
- commissural fusion
- thick, short, chordae tendinae
In rheumatic heart disease, what is the most common valve to be affected?
mitral valve
Which criteria is used for the diagnosis of acute rheumatic fever?
Jones Criteria:
- evidence of preceding streptococcal infection
- 2 major manifestations, or
- 1 major + 2 minor
What are examples of major manifestations of acute rheumatic fever?
- migratory polyarthritis (joint pain)
- myocarditis
- subcutaenous nodules
- erythema marginatum of skin
- sydenham chorea
What are examples of minor manifestions of acute rheumatic fever?
- CRP increased
- arthralgia
- fever
- elevated ESR
- prolonged PR interval
- anamnesis of rheumatism
- leukocytosis
What are the causes of aortic regurgitation?
- rheumatic fever
- infectious endocarditis
- aortic dilatations - syphilis, RA, marfan
What are the causes of mitral regurgitation?
- mitral valve prolapse e.g in marfans
- infectious
- fen-phen –> anti-obesity drug linked to heart valve problems
- papillary muscles, chordae tendinae can tear
- calcification of mitral ring
During what weeks in embryonic development does the heart develop?
week 2-7
In what week do the heart tubes fold and fuse and the heart beats for the first time?
week 3
In what week of embryological development do valves develop?
week 7
What is an ASD?
Atrial septal defect:
abnormal fixed opening in atrial septum caused by incomplete tissue formation that allows communication of blood between the left and right atria
How are ASDs classified?
According to their location:
1. Secundum (90%): due to a defective fossa ovalis (near centre of atrial septum)
- Primum (8%): adjacent to AV valves, mitral cleft
- Sinus venosus (2%): near entrance of SVC with anomalous pulmonary veins draining to SVC or RA
What is the most common congenital heart defect?
VSD (ventricular septal defect)
What other CHD do VSDs typically present with?
Tetralogy of fallot (only 30% of VSDs are isolated)
How are VSDs classified?
According to location and size:
- membranous VSD: 90% involve the membranous septum
- Infundibular VSD: 10% involve the muscular septum or lie below the pulmonary valve
What are the 4 conditions that feature in tetralogy of fallot?
- Large VSD
- Overriding aorta
- Pulmonary valve stenosis
- Right ventricular hypertrophy
Why does tetralogy of fallot occur?
due to anterosuperior displacement of the infundibular septum during embryogenesis
How can congenital heart defects can be divided?
- cyanotic (blood from right to left –> skips lungs)
- acyanotic (blood from left to right–> skips body, most common)
What are the charactertistic features of cyanotic CHDs?
boot shaped heart and squatting (increases peripheral vascular resistance)
What are 3 types of obstructive CHD?
- co arctation of aorta
- pulmonary stenosis/atresia
- aortic stenosis/ atresia
What is co arctation of the aorta?
- Congenital narrowing of the aorta usually where the ductus arteriosus inserts
- M>F 2:1
- turner syndrome (XO) frequently have it
What are the 3 types of coarctation of the aorta?
- Preductal – narrowing before ductus arteriosus
- Ductal – narrowing occurs at the location of the ductus
- Post ductal – narrowing occurs distal to the ductal
What are the features of hypoplastic left heart syndrome?
- small (hypoplastic) aorta
- atrial septal defect opening between the atria
- patent (open) ductus arteriosus
- small (hypoplastic left ventriculum)
when the aorta and left ventricle is underdeveloped
high pressure on only the right side leads to lung damage before the neonate is born
Which chromosome abnormality predisposes to VSD?
trisomy 21
Which environmental factors can increase risk of CHD?
- rubella (congenital rubella syndrome)
- gestational diabetes
- teratogens –> TORCH
