Cardio Part 1 Flashcards
What are the 2 tools that can be used for ethical dilemma analysis/consideration?
- Seedhouse’s Ethical Grid
- Create autonomy
- Respect person equally
- Respect autonomy
- Serve needs first - The Four Quadrant Approach
- Medical Indications
- Patient preferences
- Quality of life
- Contextual Features
Talk about atherosclerosis
From the Greek
athero = gruel or paste and sclerosis= hardness
- Is the principal cause of heart attack, stroke and gangrene of the extremities
- Is one of the major causes of death in Europe, USA & Japan
- The main problem is plaque rupture leading to thrombus formation, partial/complete arterial blockage leading to a heart attack
Q: which is the best-known risk factor for coronary artery diseas?
- Obesity
- Diabetes
- Gender
- Age
Age (thisss)
Tobacco Smoking
High Serum Cholesterol
Obesity
Diabetes
Hypertension
Family History
Talk about the distribution of atherosclerotic plaque.
- Found within peripheral and coronary arteries
- Focal distribution along the artery length
- Distribution may be governed by haemodynamic factors:
> Changes in flow/turbulence (eg at bifurcations) cause the artery to alter endothelial cell function. Wall thickness is also changed leading to neointima. Altered gene expression in the key cell types is key.
What are the key cell types in a plaque?
Key cell types are endothelial cells, smooth muscle cells, macrophages, fibroblasts
What are the 3 main layers of arterial wall?
Arterial wall layers are endothelium, media, adventitiia.
Q: Which of the following is not in artery walls?
Tunica intima
Tunica media
Epithelial cells
Neutrophils
Epithelial cells
This is because its endothelial cells not epithelial!
Talk about the structure of an Atherosclerotic Plaque.
An atherosclerotic plaque is a complex lesion consisting of :
- Lipid
- Necrotic core
- Connective tissue
- Fibrous “cap”
Eventually the plaque will either occlude the vessel lumen resulting in a restriction of blood flow (angina), or it may “rupture” (thrombus formation – death).
Talk about the Response to Injury hypothesis of Atherosclerosis.
First suggested in 1856 by Rudolph Virchow and updated by Russell Ross in 1993 and 1999:
- Initiated by an injury to the endothelial cells which leads to endothelial dysfunction.
- Signals sent to circulating leukocytes which then accumulate and migrate into the vessel wall.
- Inflammation ensues
What are the good sides and bad sides of inflammation?
Good side:
Pathogens
Parasites
Tumors
Wound healing
Bad side:
Myocardial reperfusion injury
Atherosclerosis
Ischaemic heart disease
Rheumatoid arthritis
Asthma
Inflammatory bowel disease
Shock
Excessive wound healing
What ignite inflammation in the arterial wall?
LDL - can pass in and out of the arterial wall
in excess it accumulates in arterial wall, and undergoes oxidation and glycation.
Endothelial dysfunction (Response to Injury hypothesis)
Talk about the stimulus for adhesion of leukocytes.
Once inflammation is initiated, chemoattractants (chemicals that attract leukocytes) are released from endothelium and send signals to leukocytes.
Chemoattractants are released from site of injury and a concentration-gradient is produced.
What are the Inflammatory Cytokines Found in Plaques?
IL-1 - canakinumab
IL-6 – tocilizumab**
IL-8
IFN-g
TGF-b
MCP-1
(C reactive protein)
What are the steps of leukocytes recruitment to vessel walls.
- Capture (selectins)
- Rolling (selectins)
- Slow rolling (selectins)
- Firm adhesion (integrin and chemoattractants)
- Transmigration (integrin and chemoattractants)
Talk about the first step in Progression of Atherosclerosis (pathology based on Stary and Virmani).
Fatty Streaks
Earliest lesion of atherosclerosis
Appear at a very early age (<10 years)
Consist of aggregations of lipid–laden macrophages and T lymphocytes within the intimal layer of the vessel wall
Talk about the step 2 in Progression of atherosclerosis.
Intermediate Lesions
Composed of layers of :
- Lipid-laden macrophages (foam cells)
- Vascular smooth muscle cells
- T lymphocytes
- Adhesion and aggregation of platelets
to vessel wall
- Isolated pools of extracellular lipid
Talk about the Step 3 in the progression of atherosclerosis.
Fibrous Plaques or Advanced Lesions
- Impedes blood flow
- Prone to rupture
- Covered by dense fibrous cap made of ECM proteins including collagen (strength) and elastin (flexibility) laid down by SMC that overlies lipid core and necrotic debris
- May be calcified
- Contains: smooth muscle cells, macrophages and foam cells and T lymphocytes
Talk about Step 4 in the progression of atherosclerosis.
Plaque rupture
- Plaques constantly grow and recede.
- Fibrous cap has to be resorbed and redeposited in order to be maintained.
- If balance shifted eg in favour of inflammatory conditions (increased enzyme activity), the cap becomes weak and the plaque ruptures.
- Basement membrane, collagen, and necrotic tissue exposure as well as haemorrhage of vessels within the plaque
- Thrombus (clot) formation and vessel occlusion
Talk about Step 5 in Progression of Atherosclerosis.
Plaque Erosion
Second most prevalent cause of coronary thrombosis
Lesions tend to be small ‘early lesions’
A thickened fibrous cap may lead to collagen triggering thrombosis rather than tissue factor (as in plaque rupture)
A platelet-rich clot may overlie the luminal surface.
There is usually a small lipid core
What are the differences between Comparison of plaque rupture and plaque erosion?
Ruptured plaque has a large lipid core with abundant inflammatory cells. Eroded plaques have a small lipid core, disrupted endothelium, more fibrous tissue and a larger lumen. Plaque rupture has red thrombus while plaque erosion has white thrombus. Red thrombus = rbcs and fibrin, white thrombus platelets and fibrinogen.
Briefly summarise the process of atherogenesis.
- Healthy vasculature
- Endothelial activation
- Early lesion
- Advanced lesion
- Atherothrombosis
- Shear stress
- Leukocyte adhesion, rolling and migration
- Cytokine release and leukocyte recruitment
- Platelet adhesion and activation
- VSMC migration and proliferation
- Fibrous cap and foam cell accumulation
- Plaque rupture and thrombosis
What is the treatment for coronary artery disease?
PCI - Percutaneous Coronary Intervention
2 million + procedures / year worldwide
More than 90% of patients require stent implantation
Restenosis was a major limitation, no longer though due to drug eluting stents
What are coronary stents used in patients today made of?
- metal
- plastic
- polymers
- Metal (usually steel or titanium)
- Polymers used in animal stent
What is the drug that is usually coated on stent?
- Sirolimus
- Reduce cell proliferation
What are some useful drugs in atherogenesis?
Aspirin – irreversible inhibitor of platelet cyclo-oxygenase
Clopidogrel/Ticagrelor – inhibitors of the P2Y12 ADP receptor on platelets and other drugs with antiplatelet actions
Statins – inhibit HMG CoA reductase, reducing cholesterol synthesis
PCSK9 inhibitors – monoclonal antibodies that inhibit PCSK9 protein in the liver which leads to improved clearance of cholesterol from the blood.
What are the specific and generic anti-inflammatory drugs for ischaemic events in patients?
Specific: an antibody called canakinumab
Generic: Colchicine
Talk about the summary of atherogenesis.
Atherosclerotic lesions are dynamic - changing with age and health status
Environmental factors are key, including genetics
Molecular mechanisms in plaques are becoming known and can be targeted with drugs.
Major cell types involved in atherogenesis are endothelium, macrophages, smooth muscle cells and platelets
Inflammation is critical in the plaque life cycle
Stents plus medical therapies have been hugely successful treatments built upon knowledge of the fundamental biology of the vessel wall
Relate smoking with atherogenesis
one cell layer endothelial layer, nicotine kills the endothelial layers, genetic background might can regenerate in some people that are smoking, but mostly not
Where in the human anatomical structure do we usually see a plaque?
in the aortic arch - usually where we see a plaque- change in flow and turbulence will lead to altered endothelial artery function
Talk about LDL and atherogenesis.
LDL getting in, making endothelial cells sticky, neutrophil and macrophage gets into the vessels wall, roll along, proliferate, lipid layer is growing, send signals and cells start to multiply and migrate and form fibrous cap, when it get large, enzyme is produced to eat the vessel walls, the blood in the lumen can get in and see a big clot, lead to MI, or can cause partial blockage; or there might be vessels remodelling
What is acute coronary syndrome?
This term covers a spectrum of acute cardiac conditions from unstable angina to varying degrees of evolving myocardial infarction (MI) which include Q wave infarction and non-Q wave infarction.
Talk about unstable angina.
*Clinical classification includes:
*Cardiac chest pain at rest
*Cardiac chest pain with crescendo pattern
*New onset angina
*Diagnosis:
> history
> ECG
> troponin (no significant rise in
unstable angina)
Talk about acute MI
*ST-elevation MI can usually be diagnosed on ECG at presentation
*Non-ST-elevation MI is a retrospective diagnosis made after troponin results and sometimes other investigation results are available
Talk about pathological Q waves in ECG.
Pathological Q waves imply a greater extend of MI, R wave is generated by viable myocardial, if you lost the viable cells - pathological Q waves
*May also be defined retrospectively as non-Q
wave or Q-wave MI on the basis of whether new pathological Q waves develop on the ECG as a result of it
*ST elevation MI and MI associated with LBBB are associated with larger infarcts unless effectively treated (and therefore more likely to lead to pathological Q wave formation, heart failure or death)
What are the possibel 3 patterns that can happen in a non-Q wave MI?
- Poor R wave progression
- ST elevation
- Biphasic T wave (up and down)
What are the symptoms of myocardial infarction?
*Cardiac chest pain
*unremitting
*usually severe but may be mild or absent
*occurs at rest
*associated with sweating, breathlessness, nausea and/or vomiting
*one third occur in bed at night
What are the risk factors of MI?
Higher risk associated with higher age, diabetes, renal failure, left ventricular systolic dysfunction (elevated NTproBNP level) and other risk factors
What are the initial management of MI?
*Get in to hospital quickly – 999 call
*Paramedics – if ST elevation, contact primary PCI centre for transfer
*Take aspirin 300mg immediately
*Pain relief
What is the hospital management for MI?
*Make diagnosis
*Bed rest
*Oxygen therapy if hypoxic
*Pain relief – opiates/ nitrates
*Aspirin +/- platelet P2Y12 inhibitor
*Consider beta-blocker
*Consider other antianginal therapy
*Consider urgent coronary angiography e.g. if
troponin elevated or unstable angina refractory to medical therapy
Talk about Atherogenesis and atherothrombosis.
- Normal (clinically silent)
- Fatty Streak (clinically silent)
- Fibrous Plaque (Angina
Claudication/PAD) - Atherosclerotic plaque (Angina
Claudication/PAD) - Plaque rupture/ Fissure and thrombosis (MI, Ischaemic Stroke, Critical Leg Ischaemia, Cardiovascular death)
Talk about the causes of Acute Coronary Syndrome.
- *Rupture of an atherosclerotic plaque and
consequent arterial thrombosis is the cause in the majority of cases - *Uncommon causes include
*stress-induced (Tako-Tsubo) cardiomyopathy - coronary vasospasm without plaque rupture
*drug abuse (amphetamines, cocaine)
*dissection of the coronary artery related to
defects of the vessel connective tissue
*thoracic aortic dissection
What is troponin?
- Protein complex regulates actin:myosin contraction
*Highly sensitive marker for cardiac muscle injury
*Not specific for acute coronary syndrome
*May not represent permanent muscle damage - Positive also in:
- gram negative sepsis
- pulmonary embolism
- myocarditis
- heart failure
- arrhythmias
- cytotoxic drugs
- …………………and more!
Talk about role of soluble platelet agonists in thrombus formation at site of vascular damage.
The endothelium is disrupted, exposure to collagen, subendothelium matrix , thrombotic response, ADP is released by platelets after binding, activated platelet has pseudopodia, easier interaction among themselves, platelet aggregation
Link Aspirin to platelet activation and blood clotting.
Aspirin block thromboxane A2, positive feedback loop is reduced, less likely blood clot will occlude the coronary artery
Irreversible inactivation of cyclo-oxygenase 1
How can we utilise the fibrinolytic system?
mimic it as a therapeutic system
What to do when there is high cholesterol due to genetic reasons and have high risk of atherogenesis?
High cholesterol is mostly genetic - too much LDL cholesterol, take statin to switch it off since you cant switch off the gene
Talk about the fibrinolytic system.
- Endothelium produces TPA (Tissue Plasminogen Activator)
- TPA catalyses the conversion of Plasminogen to Plasmin
- Plasmin catalyses the conversion of fibrin to fibrin degradation products
What are the 3 P2Y12 antagonists out there?
- Clopidogrel
- Prasugrel
- Ticagrelor
Stop the amplification of platelet activation
What is the dual antiplatelet therapy?
P2Y12 inhibitors in combination for aspirin
*Increase risk of bleeding so need to exclude
serious bleeding prior to administration
What are the examples of GP IIb IIIa?
Abciximab
Tirofiban
Eptifibatide
Talk about GP IIb IIIa antagonists.
*Only intravenous drugs available
*Used in combination with aspirin and oral P2Y12 inhibitors in management of patients undergoing PCI for ACS
*Increase risk of major bleeding so used selectively
*Reducing use globally due to more effective oral antiplatelet therapy
*Still useful in STEMI patients undergoing primary PCI to cover delayed absorption of oral P2Y12 inhibitors in these patients (due to opiates delaying gastric emptying)
Talk about anticoagulants
Used in addition to antiplatelet drugs
* Target formation and/or activity of thrombin
*Inhibit both fibrin formation and platelet activation
* Fondaparinux (a pentasaccharide) used in NSTE ACS prior to coronary angiography = safer than heparins as low level of anticoagulation used
* Full-dose anticoagulation used during PCI: options are heparins (usually unfractionated heparin; some centres use enoxaparin, a low-molecular-weight heparin) or the direct thrombin inhibitor bivalirudin (expensive, not used in Sheffield)
*High dose heparin used during cardiopulmonary bypass for CABG surgery
Talk about Overview of pharmacological
therapy in ACS.
- Initial pain relief if necessary – morphine + metoclopramide, nitrates
- Aspirin and P2Y12 inhibitor combination (assuming no contraindications
and confirmed diagnosis) - Anticoagulant: fondaparinux or heparin
- Consider intravenous glycoprotein IIb/IIIa antagonists for STEMI patient
undergoing primary PCI - Anti-anginal therapy – beta blocker, nitrates, calcium antagonist
- Secondary prevention – statins, ACEI, beta blocker, other antihypertensive
therapy - Heart failure patients – diuretic, ACEI, beta blocker, aldosterone antagonist
(spironolactone, epleronone) - Fibrinolytic therapy may be used for acute STEMI if primary PCI not
available
What is the treatment of choice for STEMI?
Primary PCI
- Predilation of occluded coronary artery
- Positioning of stent
- Deployment of stent
- Repeat angiogram after a few months
Talk about Revascularisation for NSTE ACS.
*Coronary angiography usually performed for patients with troponin elevation or unstable angina refractory to medical therapy
* PCI most frequent revascularisation procedure
*CABG surgery used in about 10% of patients with NSTE ACS
*Uncommonly, patients may have severe diffuse CAD not amenable to revascularisation
* Some patients may have no obstructive coronary artery disease due to
* Actual diagnosis not ACS
* Plaque rupture without significant stenosis and resolution of obstructive thrombus by the time of angiography
* Stress-induced (Tako-Tsubo) cardiomyopathy without obstructive
coronary artery disease
Why is clopidogrel unreliable compared to prasugrel?
Clopidogrel is a pro-drug. Activation of clopidogrel via cytochrome P450
enzymes (CYPs) and inactivation, this means the effect of clopidogrel depends on body metabolism, which some of the factors include:
- Dose
- Age
- Weight
- Disease states such as diabetes mellitus
- Drug-drug interactions e.g. omeprazole and strong CYP3A inhibitors
- Genetic variants: CYP2C19 loss-of-function alleles
What is ticagrelor?
An oral reversibly-binding P2Y12 antagonist
What are the adverse effects of tricagrelor?
*Common to all P2Y12 inhibitors:
*Bleeding e.g. epistaxis, GI bleeds, haematuria
*Rash
*GI disturbance
*Idiosyncratic
*Dyspnoea: usually mild and well-tolerated, but occasionally not tolerated and requires switching to prasugrel or clopidogrel (which are not associated with the same adverse effect but do not have the same evidence for long-term mortality reduction)
*Ventricular pauses: usually sinoatrial pauses, may resolve with continued treatment
Prasugrel vs. ticagrelor?
Better outcomes with prasugrel – but many trial limitations and better patients outcomes with ticagrelor in South Yorkshire so still some doubts
What is the Duration of dual antiplatelet therapy?
P2Y12 inhibitor may be continued for longer than 1 year after ACS if there is a high risk of further ischaemic events in aspirin-treated patients who do not have an excessive risk of life-threatening bleeding
Talk about ACS (acute coronary syndrome) management in a nutshell.
- Make the diagnosis: history, ECG, troponin +/- coronary angiography; consider other diagnoses if uncertain
- Pain relief as necessary: opiates (but can delay absorption of P2Y12 inhibitor); nitrates for unstable angina/coronary vasospasm (may be ineffective for MI)
- Check no active or recent life-threatening bleeding/severe anaemia
- If ST elevation, arrange primary PCI (PPCI) if possible
- Initial cardiac monitoring for arrhythmia
- Initial antithrombotic therapy: dual antiplatelet therapy (DAPT) + anticoagulant; may use GPIIb/IIIa antagonist for PPCI
- Revascularisation if MI or refractory/high risk unstable angina and if
feasible - Secondary prevention: DAPT duration individualised; high dose statin (e.g.
atorvastatin 40-80mg daily); blood pressure control; beta blocker if LV dysfunction, heart failure or ongoing ischaemia; aldosterone antagonist if heart failure and K+ not high
Talk about the normal structure of the heart.
- Normal weight 280-340 g male, 230-280 g female
- Two sides, right thinner than left
- Two stage electrical generated contraction
- Sarcomere proteins
- Contraction initiated by depolarisation and changes to calcium concentration
- Protein conformational change – contraction
- Removal of calcium (energy dependent) for relaxation to occur
What are the Two types of cardiac myocytes?
- Atrio-ventricular conduction system – slightly faster conduction
- General cardiac myocyte
All cells can act as pacemaker
Normal cardiac conduction
Normal coronary circulation
Blood flow through myocardium from aortic root is diastolic
Talk about Myocardial hypertrophy and heart failure.
- Normal systolic ejection fraction 60-65%
- Failure to transport blood out of heart = cardiac failure
- Cardiogenic shock = severe failure
- Frank–Starling mechanism and pericardial sac limitations
Cardiac/volume increases as venous return increases
If you exceed stretch capability of sarcomeres then cardiac contraction force diminishes
Myocardial hypertrophy can be an adaptive/ physiological response ~ athletes/pregnancy
Hypertrophic response triggered by angiotensin 2, ET-1 and insulin-like growth factor 1, TGF-β»_space;» These activate mitogen-activated protein kinase
Poor adrenergic sensitisation in cardiac failure
Some loss of cardiac myocytes during life is expected
but significant loss will impair cardiac contraction.
Talk about different type of heart failure.
Left sided cardiac failure – pulmonary congestion and then overload of right side.
Right sided cardiac failure with venous hypertension and congestion.
Diastolic cardiac failure (HFpEF) ~ Stiffer heart
Talk about Fetal embryogenesis.
The heart comprises a single chamber until the fifth week of gestation, then divided by intra-ventricular and intra-atrial septa from endocardial cushions. The muscular intra-ventricular septum grows upwards from the apex of the heart producing the four chambers and allowing valve development to occur.
Talk about congenital heart disease.
> > may complicate up to 1% of all live births.
= misplaced structures or arrest of the progression of normal structure development.
* VSD 25-30%
* ASD 10-15%
* PDA 10-20% (Patent ductus arteriosus)
* Fallots 4-10% (Tetrallogy of fallots)
* PS 5-7%
* Coarctation 5-7%
* AS 4-6%
* TGA 4-10%
* Truncus arteriosus 2%
* Tricuspid atresia 1%
Talk about the multifactorial inheritance of congenital heart disease.
One child with defect increases probability of second child with another defect.
* Single genes associated = trisomy 21 (Downs), Turner Syndrome (XO) and di-George Syndrome.
* Homeobox genes particularly associated
* Infections – Rubella
* Drugs – thalidomide, alcohol, phenytoin, amphetamines, lithium, eostrogenic steroids
* Diabetes also associated with increased risk of congenital heart disease
Talk about the classification reflect of congenital heart disease.
- cyanosis, present or absent
- whether this occurs from birth ….. or whether it develops later.
What are the types of CHD that have left to right shunt?
- VSD, ASD, PDA, truncus arteriosus, anonymous pulmonary venous drainage, hypoplastic left heart syndrome
What are the types of CHD that have right to left shunt?
- Tetralogy of Fallot, tricuspid atresia
What are the types of CHD that have no shunt?
- Complete transposition of great vessels
- Coarctation
- Pulmonary stenosis
- Aortic stenosis
- Coronary artery origin from pulmonary artery
- Ebstein malformation
- Endocaradial fibroelastosis
Talk about Eisenmenger’s syndrome.
Initial left – right shunting
Pulmonary hypertension
right side»_space; left side shunting associated with right side cardiac failure and right side cardiac hypertrophy
Talk about patent foramen ovale.
- Probe patent 17%
- Paradoxical emboli DVT»_space;> CNS infarction!
- Ostium secundum, 90% variable sized opening = central defect in central septum.
- Ostium primum type defect in lower part of septum primum
- Other types exist.
Eventually produces cardiac arrhythmias, pulmonary hypertension, right ventricular hypertrophy and cardiac failure. Risk of infective endocarditis.
Talk about Persistent/ patent ductus arteriosus (PDA),
beyond birth, is unusual, since the vessel usually occludes by fibrotic change after vascular spasm as the neonate starts breathing.
The left – right side shunting eventually means the lung circulation is overloaded with pulmonary hypertension and right side cardiac failure subsequently.
Risk of infective endocarditis.
Can be closed surgically, by catheters or by prostaglandin inhibitors (Indomethacin).
Talk about tetralogy of fallot.
Four main features
* Pulmonary stenosis
* Ventricular septal defect
* Dextraposition/over-riding ventricular septal defect
* Right ventricle hypertrophy
Characteristic boot-shape on radiology and macroscopically.
Often associated with other cardiac abnormalities.
As a result of the pulmonary stenosis, right ventricle blood is shunted into the left heart producing cyanosis from birth. Surgical correction usually is performed during the first two years of life, as progressive cardiac debility and risk of cerebral thrombosis increases.
Talk about Complete transposition of the great arteries (TGA).
This involves the aorta coming off the right ventricle and the pulmonary trunk off the left ventricle.
Male bias, and particular associated with diabetes. Survival is only possible if there is communication between the circuits and virtually all have an atrial septal defect allowing blood mixing.
Treatment = arterial switch with less than 10% overall mortality.
Talk about the coarctation of the aorta.
- This is secondary to an excessive sclerosing/obliterating process that normally closes the ductus arteriosus, extending into the aortic wall.
- The net result is a narrowing of the aorta just after the arch, with excessive blood flow being diverted through the carotid and subclavian vessels into systemic vascular shunts to supply the rest of the body.
- Particularly associated with Turner’s syndrome, and with an association with Berry aneurysms of the brain.
- Persistence of the posterior shelf.
- Discrepant blood pressures in upper and lower part of the body.
- Complications of cardiac failure, rupture of dissecting aneurysm, infective endarteritis, cerebral haemorrhage, stenosis of bicuspid aortic valve (associated).
- Treatment = dilatation (stenting) of stenosed segment.
Talk about Endocardial fibroelastosis.
- Secondary endocardial fibroelastosis = a frequent complication of congenital aortic stenosis and coarctation. Profound dense collagen and elastic tissues deposited on endocardial aspect of the left ventricle produces progressive stiffening of the heart and cardiac failure. Similar changes may affect the valves.
- Primary endocardial fibroelastosis, may follow a familial pattern.
Both are relatively rare.
Talk about Dextrocardia.
The normal anatomy of the heart is versed with rightward orientation of the access. It can occur without abnormal positioning of the visceral organs but is usually associated with severe cardiovascular abnormalities.
It is more often associated with other organ isomerism.
Talk about ischemic heart disease.
- Angina (standard, Prinzmetal/unstable, accelerated/crescendo)
- Myocardial infarction
- Chronic congestive cardiac failure ~ 75% of these patients with dilated/failing hearts reflect ischaemic heart disease
- Sudden death
Risk factors
1. systemic hypertension
2. cigarette smoking
3. diabetes mellitus
4. elevated cholesterol
Also ….obesity, increasing age, male sex, family history, oral contraceptive pill, sedentary life habit, personality features etc
What are the reasons for imperfect blood supply to the heart that can cause ischaemic heart disease?
- Atherosclerosis
- Thrombosis
- Thromboemboli
- Artery spasm
- Collateral blood vessels
- Blood pressure/cardiac output/heart rate
- Arteritis
Also anaemia, altered oxygen dissociation curve, carbon monoxide, cyanide
Increased demand from hypertension, valvular heart disease, hyperthyroidism, fever, thiamin (B1) deficiency, catecholamine stress….
Healthy individual has coronary reserve 4-8 times of resting blood flow
Coronary arteries have no resistence in practical terms
Constriction/dilation of small intramyocardial branches, < 400 µm diameter.
For relatively limited foci of stenosis up to 75% of cross section coronary artery architecture can be lost without impairment of blood flow.
At 90% limited blood supply during exercise/demand may be significant.
What are the other conditions that limit coronary flow?
- Coronary arteritis
- Dissecting aneurysm of aorta
- Syphilitic aortitis, congenital abnormality of coronary artery origin
- Myocardial bridge
What are the different pattern of infarction?
- Subendocardial/patchy infarction (type 2)
- Transmural infarction. (type 1)
Complications of infarcts differ according to which territory has compromised.
Dating of myocardial infarction
Talk about Reperfusion of ischaemic myocardium.
Followed the development of clot-busting agents and angioplasty techniques. Reperfusion of completely infarcted tissue can produce significant haemorrhage. The reperfusion allows oxygen delivery and a further degree of injury as a result of generation of superoxide radicals etc.
What are the pathological complications of ischaemic damage?
- Arrhythmias (supraventricular and ventricular)
- Left ventricular failure – cardiogenic shock.
- Generally reflects >40% muscle damage
- Extension of infarction, rupture of the myocardium (into pericardial space, between chambers, across papillary muscle insertion)
Talk about Aneurysm.
This is a dilation of part of the myocardial wall, usually associated with fibrosis and atrophy of myocytes.
Variable fatty tissue replacement may also occur.
The dilatation of the thin walled sac allows blood stasis and thrombosis.
Risk of subsequent embolism of such material.
Talk about pericarditis.
Pericarditis (Dressler syndrome).
Inflammation of the sac surrounding the heart (pericarditis). It’s believed to occur as the result of the immune system responding to damage to heart tissue or damage to the sac around the heart (pericardium). The damage can result from a heart attack, surgery or traumatic injury.
This is a delayed pericarditic reaction following infarction (2-10 weeks).
All therapeutic models aim to improve blood supply along the coronary vessels affected, and to restore blood to ischaemic parts of the myocardium.
* Thrombolytic enzymes
* Percutaneous translumenal coronary angioplasty (PTCA)
* Coronary bypass grafting
* Other techniques (laser – drill)
* Stents
* (transplantation)
Talk about hypertension effect on the heart.
- WHO classification >140/90 mm Hg. Hypertensive heart disease – reflects cardiac enlargement due to hypertension, and in the absence of other cause.
- Compensatory hypertrophy of the heart initially with increased myocyte size, squaring of the nuclei and slight increase of the interstitial fibrous tissue.
Initially able to handle the increased workload, eventually the hypertrophy no longer compensates. - Falling amount of oxygen delivery to cardiac myocytes produces further fibrosis and progressive contractile dysfunction.
- Often associated with coronary atheroma and ischaemic heart disease – aggravating situation.
- Particularly associated with fatal intracerebral haemorrhage.
Talk about Cor pulmonale.
= Right ventricular hypertrophy and dilatation due to pulmonary hypertension.
May reflect an acute event.
* Embolisation of material into the pulmonary circuit, but is more common chronically reflecting a variety of lung disorders.
* Chronic bronchitis and emphysema
* Pulmonary fibrosis
* Cystic fibrosis
* Recurrent emboli
* Primary pulmonary hypertension
* Peripheral pulmonary stenosis
* Intravenous drug abuse
* High altitude
* Schistosomiasis
* Abnormal movement of the thoracic cage (Pickwickian syndrome, kyphoscoliosis, neuromuscular disorders etc).
Classically disproportionate right ventricular hypertrophy as compared with the left.
Progressive features of right side cardiac failure with venous overload, peripheral oedema and progressive hepatic congestion.
Talk about acute rheumatic fever.
Group A β-haemolytic streptococcus infection
usually upper respiratory tract.
Remains a major factor with regard to heart disease in the developing world.
Peak age of pathology 9-11 years, but can occur in adults.
Development of immunity against the streptococcal pharyngitis produces antibodies that cross react with cardiac myocytes and valvular glycoproteins.
This produces localised inflammation and subsequent scarring.
Clinical features:
Carditis, (cardiomegaly, murmurs, pericarditis and cardiac failure) polyarthritis, chorea, erythema marginatum and subcutaneous nodules.
Minor criteria for diagnosis include:
previous history of rheumatic fever, arthralgia, raised CRP, ESR and white cell count.
Antibodies against group A streptococcal antigens, anti-streptolysin O, anti-DNAse B and anti-hyaluronidase.
Symptoms and features diminish after 3-6 months.
Some patients die acutely and are shown to have granulomatous foci of inflammation (Aschoff body, Anitchkov cells and some giant cells). There may be pericarditis and endocarditis.
What are the complications of Acute rheumatic fever?
Chronically scarring and deformity produces contracture of the valve and chordae tendinae. These may subsequently calcify and distort blood flow allowing localised thrombosis. They also provide ideal settling sites for bacteria within the blood stream, and the development of infective endocarditis.
»> Progressive cardiac dysfunction as a result of the slowly distorting valvular function.
What are some other diseases that affect cardiac valves?
SLE, rheumatoid arthritis, ankylosing spondylitis and other connective tissue disorders.
