Cardiovascular Module PDF

🧪 Cardiovascular Module Cellular and Systematic Pathology Date @November 14, 2024 Lecturer Dr J Nicol Week Week8-9 Learning Objectives Normal blood vessel structure...

🧪 Cardiovascular Module Cellular and Systematic Pathology Date @November 14, 2024 Lecturer Dr J Nicol Week Week8-9 Learning Objectives Normal blood vessel structure The process of haemostasis, thrombosis & embolism The process of atherosclerosis & its functional consequences The prevalence, signs, symptoms and treatment of peripheral vascular disease Factors that determine blood pressure – CO & TPR, sympathetic & parasympathetic nervous systems & Renin-Angiotensin-Aldosterone (RAA) system The prevalence, categorisation & definition of hypertension The difference between primary and secondary hypertension and possible causes The potential consequences of hypertension The main features of a hypertensive crisis & malignant hypertension The main features of both acute and chronic diseases of veins The features, diagnosis and treatment of pulmonary embolism Cardiovascular 1  Cardiovascular disease Major cause of death in the western world 48% of all deaths in Europe - 4 million /yr Serious healthcare resource implications levels of obesity increasing levels of diabetes increasing increasing elderly population 200,000/yr deaths in UK alone It is also a major cause of disease in other developed countries. Why do you think that is? Diets are generally improving in Northern and Western Europe but deteriorating in Southern and Central Europe. Obesity is increasing across Europe. Diabetes is increasing across Europe Functions of the endothelium Cardiovascular 2  Regulates smooth muscle tone Regulates permeability of vessel wall Defence against pathogens Provides an anti-thrombolytic surface & involved in haemostasis ROLE OF NITRIC OXIDE Nitric Oxide –powerful vasodilator released from endothelial cells ↑ diameter of coronary arteries ↑ blood flow to myocardium. Cardiovascular 3  CARDIOVASCULAR DISORDERS Narrowing (or blockage) of the arteries reduces blood flow to tissues. Possible causes are atherosclerosis, thrombosis or embolism. Haemostasis Cardiovascular 4  Three events occur: 1. Vascular spasm - neurally mediated vasoconstriction 2. Primary haemostatic response - platelet plug formation; platelets join together and change shape to plug wound 3) Secondary haemostatic response - blood clotting; activation of the coagulation cascade, formation of a thrombus Haemostasis can be triggered by damage to a blood vessel or by events occurring out with the blood vessel within the tissue giving rise to production of a tissue factor. Thrombosis Inappropriate spontaneous formation of a haemostatic plug in the absence of bleeding (e.g. damage to the endothelium) Cardiovascular 5  A pathological problem, can cause blockage of blood vessels Arterial thrombus –”white thrombus”; consists mainly of platelets and leukocytes in a mesh of fibrin; associated with atherosclerosis Venous thrombus – “red thrombus”; similar to blood clot; consists mainly of red blood cells and fibrin (e.g. deep vein thromboses (DVTs)) Parts of a thrombus can break off (whether arterial or venous) forming an embolus that lodges in the lungs or coronary vessels etc. This can be fatal. Embolism This is an abnormal mass of matter that enters a vessel and causes blockage in a smaller vessel Solid – blood clot, fat, bone marrow following fracture Liquid – amniotic fluid entering maternal circulation during childbirth due to high intra-abdominal pressure Gaseous – air from lungs Abnormal mass of matter that gets lodged in a blood vessel. Comes from within the vascular system. Matter entering the vessel could be - Solid, Gaseous, Liquid. Cardiovascular 6  Classes of lipoproteins Chylomicrons – Transport tri-glycerides (TGs) and cholesterol (C) from GI tract to tissues where TGs are released and remnants are taken to the liver for storage, creation of bile acids or released into: Lipoproteins have a central core of hydrophobic lipids surrounded by a hydrophilic coat of phospholipids, free cholesterol and apolipoproteins. There are 4 main classes: Very low density lipoproteins (VLDLs) – transport C and new TGs to the tissues including fat and muscle, where TGs are removed as before, leaving: Low density lipoproteins (LDLs) – mainly C, which is taken up by tissues and some by liver via specific LDL receptors High density lipoproteins (HDLs) – absorb C from cell breakdown in tissues (including arteries), convert it to cholesterol esters and transfer it to LDLs and VLDLs High plasma levels of LDLs and low plasma levels of HDLs increases risk of atherosclerosis High plasma levels of HDLs and low plasma levels of LDLs is protective Pathophysiology of atherosclerosis development Initial injury to endothelium – many causes e.g. high BP, increased LDL, reduced HDL, diabetes. Endothelium becomes inflamed Macrophages are attracted to the area and release inflammatory mediators such as CRP, TNF-α Free radicals oxidise LDL Macrophages engulf Cholesterol & LDL to form foam cells that move into the intima Cardiovascular 7  Fatty streaks are formed Macrophages release growth factors that stimulate proliferation (growth) of underlying smooth muscle Collagen is deposited over the fatty streak Plaque develops Cardiovascular 8  Effect of plaque accumulation The fibrous plaque can calcify and protrude into the vessel lumen and decrease blood flow. Some plaques are unstable & may rupture That will result in initiation of platelet accumulation & adhesion, blood clotting and formation of a thrombus (clot). Blood flow can be severely compromised leading to acute coronary syndrome (ACS) Atheromas Can result in Ischaemic Heart Disease (IHD) [coronary blood vessels no longer allow sufficient blood flow], Peripheral Vascular Disease (PVD) [occurs when vessels supplying extremities are affected] & Cerebrovascular disease (CVD) & Aneurysms (A) [damage to a major blood vessel] Risk Factors Hyperlipidaemia Cardiovascular 9  Hypertension Diabetes mellitus Obesity Age Male sex Family history Smoking The first 3 risk factors are the triad of conditions that increase the risk x20 Cardiovascular 10 Cardiovascular 11  Atheromatous Lesions dependent upon - anatomic location, age & sex, exposure to risk factors Risk Factors; Hypercholesterolaemia Cigarette Smoking, Hypertension, Diabetes VASCULAR EFFECTS OF ATHEROMA - ANEURYSM Weakness in blood vessel wall as plaque erodes wall, ↑ inflammation, enzymes released Peripheral vascular disease Most common cause of PVD is atherosclerosis Mainly affects the lower extremities, flow of blood to areas obstructed Superficial femoral and popliteal arteries most often affected Lesions affecting lower leg and foot mainly due to obstruction of tibial, common peroneal and pedal vessels Cardiovascular 12  PVD - WHO DOES IT AFFECT? Most common in men >60 years old About 1 in 5 of population >65 years Risk factors similar to those in atherosclerosis i.e. advanced age, male sex, diabetes, smoking Gradual process, at least 50% occlusion before ischaemic symptoms arise Primary symptom is “intermittant claudication” i.e. pain on walking Affects 1 in 20 of those >65 Calf pain most common as gastrocnemius muscle most active in walking Cardiovascular 13  SIGNS AND SYMPTOMS Pain on walking Thinning of skin and subcutaneous tissues on lower limbs Progressive atrophy of leg muscles Cool foot with weak or absent popliteal or pedal pulses Blanching of limb on elevation and reddening when dependent (effect of gravity on perfusion pressure) Progression to pain at rest, ulceration and gangrene May lead to amputation DIAGNOSIS OF PVD Physical examination for visible signs Palpation of femoral, popliteal, posterior tibial and dorsalis pedal pulses Ankle-to-arm ratio (tibial and brachial systolic pressures, ratio of 0.9 indicates occlusion) Doppler ultrasound detection of pulses Cardiovascular 14  MRI arteriography, CT arteriography, contrast angiography TREATMENT OF PVD Treatment has 2 main goals: 1) to reduce risk of cardiovascular events 2) to reduce symptoms Cardiovascular risk lowered by drugs such as those used in atherosclerosis therapy i.e. Anti-platelet agents, lipid lowering drugs, anti-hypertensives etc. Also lifestyle changes Patients advised to “walk through” the claudication to encourage development of collateral vessels Surgery e.g. femoropopliteal by-pass, angioplasty or balloon catheterisation, reserved for those with disabling claudication Blood pressure The pressure waves exerted on the vessels by the blood as it is ejected from the heart which is given as two figures: Upper – systolic, heart contracts Lower – diastolic, heart relaxes between beats Blood pressure = cardiac output x total peripheral resistance Must be maintained within tight limits ARTERIAL BLOOD PRESSURE Cardiovascular 15  Systolic/diastolic Ideally 120mmHg/80mmHg PRESSURE WAVE IN SYSTEMIC ARTERIES Vascular resistance Arteries contain a thick layer of circular smooth muscle Cardiovascular 16  This can respond to activation of the sympathetic nervous system (and some chemical vasoconstrictors e.g. adrenaline, thyroid hormones) by contracting This narrows the lumen of the vessel causing a reduction in blood flow i.e. the resistance to normal blood flow is increased, (so total peripheral resistance is increased) Small adjustments to vessel radius results in substantial changes in resistance so if the diameter of the lumen is reduced by constriction, thickening or blockage of the vessel wall this also increases resistance to normal blood flow. Effects of autonomic NS on BP Fight or flight Sympathetic nerves release Noradrenaline- acts on beta1- adrenergic receptors in heart Increased heart rate Acts on alpha1- adrenergic receptors in vessels Increases smooth muscle tome Rest and restore Parasympathetic nerves release Acetylcholine- acts on M2(muscarinic)receptors Decreases heart rate Factors affecting BP Cardiovascular 17  Hormonal influences on blood pressure 1. Sympathetic Nervous System - ↑CO & vasoconstriction 2. Antidiuretic Hormone (ADH) - vasoconstriction 3. Atrial Natriuretic Peptide (ANP) – vasodilation & salt & H2O loss in urine 4. Renin – Angiotensin – Aldosterone (RAA) system - ↑reabsorption of Na+ & H2O & vasoconstriction 5. Erythropoietin via effects on RBC production & ↑ blood viscosity RENIN ANGIOTENSIS ALDOSTERONE (RAA) SYSTEM Cardiovascular 18  Demonstrates the substances involved which have an impact on blood pressure. Blood pressure categories Hypertension STATISTICS 32% of men and 30% of women have hypertension. Most important risk factor for coronary heart disease CHD (the UK 's leading cause of premature death), stroke, diabetes and chronic kidney disease. Cardiovascular 19  People may not be aware they have it as it has no symptoms. This has earned hypertension a reputation as the ‘silent killer'. As many as 70% of adults, in UK, with Type 2 diabetes have hypertension. Tackling hypertension is essential to those national strategies for CHD, stroke, diabetes and chronic kidney disease. DEFINITION Hypertension is defined as a persistent raised blood pressure of over 130-139 systolic and/or 80-90mmHg diastolic. Most forms of primary hypertension are due to elevated total peripheral resistance (TPR), therefore a result of increased smooth muscle tone in the vessels A lot of treatments for high blood pressure is to increase relaxation of smooth muscle in blood vessels. TYPES OF HYPERTENSION Essential/Primary hypertension (90-95% of all cases) No known cause Associated with: +40 years, Obesity, Physical inactivity, Smoking/alcohol, Genetic predisposition Secondary hypertension (5-10% of cases) Renal disease (activation of RAAS) Endocrine disease e.g. phaeochromocytoma - high levels of catecholamines Primary hyperaldosteronism - increased blood sodium Cushing syndrome - gluco & mineralo-corticoid effects Cardiovascular 20  Congenital adrenal hyperplasia - Rare enzyme deficiencies so deficient in cortisol, ↑ ACTH stimulates adrenal androgens COMPLICATIONS OF HYPERTENSION ESSENTIAL / PRIMARY HYPERTENSION Insidious onset, generally asymptomatic Common Clinical Manifestations Chronic headaches - last for days Dizziness or Vertigo Blurry or double vision. Drowsiness Nausea Shortness of breath. Cardiovascular 21  Heart palpitations Fatigue - general tiredness Nosebleeds A strong need to urinate often (especially during the night) Tinnitus (a ringing or buzzing in the ears) EFFECTS ON HEART Concentric left ventricle hypertrophy Variable with poor correlation to pressure Individual variation - some can double in size, others hardly change to the same pressure Hypertrophied ventricle stiffer - with poor relaxation and poor filling Increased distance between myocyte and blood supply - increased diffusion distance EFFECTS ON ARTERIES Tunica media thickens with smooth muscle hypertrophy Greatest effect is in small resistance vessels Longstanding pressure gives rise to arteriosclerosis Medial smooth muscle is replaced by collagen Loss of arterial compliance Increased systolic pressure Thickened intima accompanies dilation EFFECTS ON ARTERIOLES Cardiovascular 22  Chronically - Arteriolosclerosis Some vascular beds affected more than others e.g. retina, kidney Glomerular arterioles most severely affected - results in increased permeability or filtration pressure Sclerosis of the glomeruli and atrophy of nephrons Thickening of the arteriolar wall with characteristic ‘onion skin’ lesion in kidney of patient with severe hypertension HYPERSENSITIVE KIDNEY COMPLICATIONS AND PROGNOSIS OF HYPERTENSION Cardiovascular 23  Progression of atheroma Cardiac failure Cerebral haemorrhage Aneurysms Development of malignant hypertension. HYPERTENSIVE CRISIS AND MALIGNANT HYPERTENSION Rare, affecting approx. 1% population with hypertension, but it is potentially fatal Hypertensive crisis is presentation with sudden steep rise in BP (>180/>120 mmHg) but can be differentiated: with no end organ damage is known as hypertensive urgency with presence of end organ damage is known as hypertensive emergency/malignant hypertension. Further damage to arterial tree, tissue damage plus increases risk of thrombosis Symptoms -- Headache, visual disturbances, nausea, chest pain, numbness or weakness in arms/legs, shortness of breath, reduced urine output, cardiac & renal failure etc. Complications include brain damage (stroke/seizure), cardiac damage (angina, heart failure, arrythmias), kidney failure, blindness, fluid in lungs Multiple causes - e.g. renal (renal artery stenosis, glomerulonephritis etc.) or endocrine disease (phaeochromocytoma, Cushings etc.), coarctation of the aorta (congenital narrowing of aorta), central nervous system disorders (e.g. head injury, cerebral infarction/haemorrhage), pregnancy (pre-eclampsia), withdrawal of anti-hypertensives, drugs including recreational drugs (e.g. cocaine, amphetamines) Who is at risk? - Younger patients at higher risk than older ones, Individuals of African American heritage, men and smokers are at higher risk Cardiovascular 24  Contributing factors - Accelerated disease in anyone with a history of kidney failure or renal artery stenosis Survival - 5-year survival with treatment approx. 75-84%; If untreated average survival is less than 2 years Chronic diseases of veins Leg varicosities very common during pregnancy or obesity (both due to increased intra-abdominal pressure), or in occupations that involve heavy lifting or prolonged standing Incidence rises with age, 50% in people >50 years Most common in females 30 to 50 years, especially with familial predisposition Prolonged exposure to this increased pressure causes valves to become incompetent so reflux causes further enlargement Blood vessels becomes dilated, wall thins leading to stretching and bulging Varicose veins resulting in aching legs and oedema. Acute diseases of veins Venous thrombosis, or thrombophlebitis – the presence of a thrombus and accompanying inflammation in the vessel wall Most common in older individuals Can be superficial or deep (with more serious consequences) Affects mainly lower limbs, common after operations and recumbent illnesses e.g. deep vein thrombosis –DVT Caused by factors identified by Virchow’s triad (see next slide) Can present as inflammation i.e. pain, swelling, muscle tenderness, fever, malaise, elevated white cell count Cardiovascular 25  Can occasionally be initially asymptomatic (50% of cases), possibly because vessel is not completely occluded Risk factors for venous thrombosis Vessel wall injury Endothelial damage (e.g. smoking, immune activity, inflammation) Trauma, surgery, catheters Hypercoagulability Deficiencies of anti-coagulant proteins (e.g. anti-thrombin III, protein S) Dehydration (e.g. concentration of clotting factors) Oral contraceptives , HRT Stasis Immobility (e.g. paralysis, bed rest following illness, long sedentary travel) Cardiovascular 26  Pulmonary embolism Emboli can be thrombus from injury, accidentally injected air, fat from bone marrow or amniotic fluid from ruptured membranes at time of delivery Pulmonary emboli arise when blood borne substance lodges in the pulmonary artery and blocks blood flow Most occur from deep vein thrombosis (DVT) of lower limbs, especially in patients who have been bedridden or with limited mobility (aircraft passengers etc.) Smokers and females on HRT at most risk Symptoms depend on location of obstruction but include chest pain, dyspnoea and increased respiratory rate DIAGNOSIS Pulmonary emboli can be fatal (often rapidly so) Early detection and treatment is essential Diagnostic tests include venography, ultrasonography, a pulmonary ventilation/perfusion scan (V/Q scan) and D-dimer assessment With increasing awareness of situations known to promote DVTs and pulmonary emboli the focus is now on prevention strategies TREATMENT Main emphasis is on prevention of DVTs e.g. use of graded compression elastic stockings (flight socks) Early mobilisation of patients following surgery or childbirth Also prophylactic use of anti-coagulants e.g. low molecular weight heparin to bed-ridden in hospital Cardiovascular 27  Treatment of existing emboli with thrombolytic (clot buster) therapies (e.g. streptokinase, recombinant tissue plasminogen activators, tPA) and anti- coagulants e.g. heparin Also surgical procedures to reduce the risk of emboli travelling to lung e.g. venous ligation ISCHAEMIC HEART DISEASE Learning objectives You should understand: Epidemiology and Risk factors for IHD Features of the normal heart and coronary blood supply Clinical presentation of IHD Acute Coronary Syndrome including NSTEMI & STEMI Cellular changes & Structural changes Effects of myocardial necrosis Sudden death & complications of acute infarction Epidemiology Major cause of death in Western countries. UK’s biggest killer – 146000 heart attack cases Every 6mins someone dies from a heart attack Every 11mins a man dies from a heart attack Every 13mins a woman dies from a heart attack Serious healthcare resource implications Cardiovascular 28  Predominantly due to ‘Life-style’ -25% of all men and women in UK are obese, 30% of children in UK are overweight or obese Inherited hyperlipidaemias & diabetes Risk factors Increasing age Male gender Raised plasma cholesterol / Hyperlipidaemia Raised blood pressure Smoking Diabetes mellitus Increased levels of certain clotting factors Obesity Lack of exercise Physiological features of normal heart Energy Requirements are high Limited endogenous fuel stores e.g. ATP Heart requires continuous good blood supply to maintain ATP levels Uses 80% of available oxygen in coronary blood supply Increased work needs more myocardial blood supply Interruptions in blood supply can have dire results Cardiovascular 29  Coronary blood supply Perfusion is unusual: In coronary arteries perfusion occurs due to pressure in aorta (pressure generated by heart) Myocardial blood flow low is regulated mainly by need of cardiac muscle for oxygen (many metabolites are vasodilatory, particularly adenosine) Heart influences own blood supply by compressing intramyocardial and subendocardial vessels during systole Exercise mediates increased flow by relaxation of small arteries and arterioles and during strenuous exercise demand for O2 increases and coronary flow increases x4 Any blockage limits blood supply to a clearly defined region Clinical presentation Stable Angina – predictable pain on exercise e.g. climbing stairs Unstable Angina – unpredictable chest pain Myocardial Infarction (MI) – NSTEMI & STEMI Myocardial necrosis Sudden death Consequences of coronary artery atherosclerosis Cardiovascular 30  Layers of cardiac wall Subendocardial / transmural Cardiovascular 31  These terms are a description in terms of pathology - damage may affect endocardium, myocardium or epicardium of all of these If damage affects whole wall – transmural or if damage is more limited it might be sub endocardial. Damage may depend on any reperfusion that occurs. Note: reduction of blood flow→ hypoxia→ tissue necrosis is a spectrum Cardiovascular 32  Consequences of plaque STABLE ANGINA The fibrous plaque can calcify and protrude into the vessel lumen and decrease blood flow. Narrowing of a coronary artery due to atherosclerosis and/or coronary vasospasm that is transient and usually resolves with rest is stable angina where a stable plaque reduces blood flow Cardiovascular 33  Predictable chest pain when O2 demand exceeds a known level - (walking up stairs). 50% reduction in width this equates to 75% reduction cross sectional area Can be treated using nitric oxide donors (e.g. glyceryl tri-nitrate) which are metabolized to yield nitric oxide (potent vasodilator) or by coronary angioplasty ACUTE CORONARY SYNDROME Some plaques are unstable & may rupture That will result in initiation of platelet accumulation & adhesion, blood clotting and formation of a thrombus (clot). Disruption of a plaque can result in acute coronary syndrome ranging from unstable angina to a myocardial infarction. If an unstable plaque ruptures and platelets adhere and blood clotting occurs followed by thrombosis this is called unstable angina which may progress to a myocardial infarction Effects depends on the extent and duration of occlusion ~ UA, NSTEMI AND STEMI ~ If an atherosclerotic plaque is ruptured and blood clotting is triggered this may obstruct a coronary vessel leading to ischaemia (reduced oxygen) or infarction (damage) or necrosis (cell death). Unstable angina (UA) - Reversible cardiac ischaemia - Perfusion is restored before significant damage to myocardium occurs Non-STEMI : blood flow is interrupted resulting in damage to myocardium directly under the endocardium (inner layers). Clot formation occurs over plaque. No ST elevation occurs in ECG STEMI : continuing coronary occlusion by clot can result in damage extending from the endocardium to the epicardium (through cardiac wall Cardiovascular 34  transmural MI). ST elevation occurs in ECG ~ UNSTABLE ANGINA ~ Unpredictable chest pain e.g. pain may occur at rest differs in frequency, intensity and character Over first 3 months 4% of patients will die suddenly 15% will suffer a myocardial infarction some will undergo spontaneous remission Anti-platelet drugs, e.g. aspirin and clopidogrel, appear to have a beneficial effect Biomarkers of cardiac damage Levels of troponin are markers of necrosis of cardiac myocytes. cTNT & cTNI are usually assessed The presence of creatinine kinase-MB is also indicative of myocardial injury Their presence are an indication of cardiac proteins being released from the damaged cardiac myocytes and diffuse into the interstitial spaces and then into the blood. *Remember basic muscle physiology - calcium binds to troponin Cardiovascular 35  BIOMARKERS IN ACS UA – no markers as flow restored NSTEMI may have markers if myocardium injured but not necessarily necrosis but risk of recurrent clot formation STEMI - ischaemic damage and death of cardiac tissue, extent of damage depends on how much tissue is affected, length of occlusion, tissue requirements, collateral vessels. Greater risk of cardiac dysfunction Cardiovascular 36  General pathology Information on blockages gained through post-mortem exam and experimental animals Myocardium starved of a blood supply rapidly ceases to contract Consequences of an infarct influenced by coronary artery anatomy and collateral blood flow Damage is time dependent ECG abnormalities help in diagnosing Cardiovascular 37  Cellular, biochemical and structural changes due to ischaemia GENERAL Oxygen levels fall Cardiac enzymes found in blood Mitochondrial oxidation fails Cardiovascular 38  ATP rapidly decreased to 0 by 40-60mins Lactate levels increase – anaerobic respiration Creatine phosphate falls to 0 within 15 minutes Increased H+ levels inhibit myosin ATPase Decreased fatty acyl CoA can disrupt cell membranes All of these lead to lack of contraction INITIAL 0 - 12 hours - Infarct not grossly visible However, at 30+ mins: Ultrastructural damage Reduced glycogen granules Cellular chromatin appears dense Mitochondria swell in size Golden hour for treatment – either thrombolysis or primary percutaneous coronary intervention (PPCI) 1-2 hours - beginning of irreversible damage - membrane blebbing At this stage improving blood flow to the tissues can cause severe reperfusion injury FURTHER 4-12 - hours beginning of coagulation necrosis Detectable levels of serum cardiac markers e.g. myoglobin, creatinine kinase (CK-MB) and troponins (Troponin I & Troponin T) Cardiovascular 39  MI - 12 to 24 hours after Infarcted area is pale with blotchy discolouration. Coagulation necrosis, oedema, neutrophilic infiltration and contraction band necrosis. MI - 24 to 72 hours after Cardiovascular 40  Macroscopically area appears pale Light microscopy changes occur Heavy neutrophilic presence Complete coagulation necrosis of fibres Loss of muscle striation MI - 3 to 10 days after Macrophages appear Early disintegration and phagocytosis of necrotic fibres Dead muscle appears shrunken and yellow. Granulation tissue at the edge of the infarct MI - weeks to months after Cardiovascular 41  Over time, progressive collagen deposition Collagen fibres replace damaged muscle fibres Collagen cannot contract and cannot conduct electrical impulses - problems with heart function (arrhythmias) Sudden death due to ischaemia Death within 6hrs of the onset of symptoms in a previously symptom-free patient, accounts for 60% of such fatalities. 50% of patients dying suddenly from IHD are said to have been unaware that they had CVD Primary cause is ventricular fibrillation e.g. action potentials being generated from several ectopic sites - no co-ordination, heart wriggles like bag of worms, no pumping activity Increased levels of intracellular cardiac enzymes Complications of acute infarction Myocardial rupture - occurs in three forms: 1) External myocardial rupture 2) Rupture through intraventricular septum (tissue that divided left and right sides) 3) Rupture of papillary muscles (muscles that are attached to valves) Other complications: Arrhythmias Cardiovascular 42  Acute pericarditis (inflammation of the outer covering of heart) Cardiovascular 43