Cardiovascular

• blood pump into ventricles from atrium

atrial systole

• ventricular volume remains constant

Isovolumetric ventricular contraction

• right ventricle ejects deoxygenated blood into lungs and left ventricle ejects oxygenated blood to systemic circulation.

Ejection.

• Both sets of valves are closed. Ventricles relax.

Isovolumetric ventricular relaxation.

• AV valve are forced open, blood rushes into the relaxing ventricles

Passive ventricular filling.

• in between depolarisation and repolarisation 

• influx of calcium - plateau 

phase 3 of action potential

• pauses in action potential

• increase in this means the heart slows down

effective refractory period

• Recording of the electrical activity of the heart

• Electrodes attached to the surface of the body which detect electrical changes in myocardial cells

• Contraction of any myocyte indicate electrical changes called depolarisation

• used to detect electrical disturbances & abnormalities in heart rhythm

ECG

• Atrial depolarisation

p wave

• Ventricular depolarisation

QRS complex

• Ventricular repolarisation

T wave

• Atrial depolarisation to ventricular depolarisation to ventricular repolarisation

• SA node to atrium to AV node to purkinje fibre to ventricles. 

steps in a normal ECG

• Volume & pressure generated in the ventricle at the end of diastole

• Ventricular end-diastolic volume (VEDV)

• determined by Venous return during diastole and End-systolic volume (remaining blood after contraction)

• Causes lengthening of the myocardial fibres = ventricular stretch

pre-load

• ‘The ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return

• Length-tension relationship of preload to myocardial contractility

Frank-Starling mechanism

• The force needed to be generated to eject blood from the heart

• Varies depending on systemic vascular resistance and ventricular wall tension
  Increase vascular resistance causes am  increase afterload , decrease SV and  increase end systolic volume

afterload

• force of contraction

• Interaction between actin and myosin filaments during cardiac muscle contraction

• Needs energy from ATP, Ca, Na & K •

• Relates to Frank Starling mechanism

Inotrophy

• Influx of Ca2+

• Triggers Ca2+ release from scarcoplasmic reticulum (SR)

• Ca2+ binds to troponin C causing contraction of myofibrils (systole)

• Reuptake of Ca2+ into sacroplasmic reticulum

• Ca2+ efflux of by Na+ / Ca2+ exchange transporter causing relaxation (diastole)

myocardial contractibility

• Increase contractility causes an Increase CO

• CO= The volume of blood pumped out of the heart per minute

• CO = SV x HR

• CO is changed by alterations in SV or HR

effect of cardiac contractibility on cardiac output

• amount of blood pumped out of the ventricle with each contraction

Ejection Fraction (EF) %

• pressure during ventricular contraction

systolic BP

• pressure during ventricular filling / relaxation

Disatolic BP

• regulated to maintain total plasma volume (TPV) and tissue perfusion

Arterial pressure

• RAAS

• ADH

• Natriuretic Peptides

• Aldosterone

factors that maintain the total plasma volume (TPV)

• Determined by changes in diameter of the arterioles

• Vasoconstriction increases pressure

• Vasodilatation decreases pressure

• Baroreceptors

• Hormonal control –RAAS –ADH

peripheral resistance 

• secreted from juxtaglomerular apparatus in kidney

Renin

• secreted from liver

Angiotensinogen

• secreted from the lungs

ACE

• secreted from posterior pituitary gland

ADH

• A sustained elevation of systemic arterial blood pressure (BP)

• Results from a sustained increase in peripheral resistance, increase in blood volume or both.

hypertension

• Elevated BP with unknown cause 

• Most common

• 90-95% of all cases 

• Combination of systolic and diastolic HTN

• risk factors - Cigarette smoking , Diabetes Mellitus , Excess sodium intake , Gender , Elevated serum lipids , Family history

primary hypertension

• Elevated BP with known, specific cause

• Less common

• 5-10% of all cases

• Caused by an underlying disease, eg renal disease

secondary hypertension

• Chronic kidney disease

• Stroke

• Transient ischaemic attack (TIA)

• Peripheral arterial disease (PAD)

• Left ventricular hypertrophy (LVH)

• Angina 

• Myocardial infarction (MI)

• Heart failure (HF)

complications of hypertension

• elevated cholesterol 

• specific kind of arteriosclerosis - the pathological build up of fatty lesion

Atherosclerosis

• chronic disease of the arterial system characterised by abnormal thickening & hardening of wall of vessels

• Tunica intima - layer of vessel affected 

• affects heart, brain, kidney, lungs, liver, limbs

• decrease blood flow 

• causing ischaemic Heart Disease and Myocardial Infarction

Arteriosclerosis

• Hypertension

• Smoking

• Increased low-density lipoprotein & decreased high - density lipoprotein cholesterol 

• Elevated C-reactive protein

• Increased serum fibrinogen

• Diabetes

• Oxidative stress 

• Infection

risk factors of Atherosclerosis

• (in tunica intima)

• Atherosclerosis begins with injury to endothelial cells (ECs) • Injured ECs become inflamed 

• Inflamed ECs CANNOT make normal amount antithrombic agents and vasodilating of cytokines

Endothelial cell injury (steps of atherosclerosis) 1

• Macrophages adhere to injured EC lining

• And release inflammatory cytokines (eg TNFalpha, C-reactive protein)

Adhesion to Endothelium  (steps of atherosclerosis) 2

• Further recruitment of monocytes which differentiate into macrophages

• Lipids accumulated in the vessel intima. 

• Macrophages penetrate intima and engulf lipids

• Macrophages filled with lipids are called FOAM CELLS

Foam cells (step 3)

• Accumulation of foam cells form a lesion called FATTY STREAK

Fatty Streak(step 4)

• Macrophages also release growth factors - increase proliferation of smooth muscle cells (SMCs)

• SMCs migrate to intima

• SMCs in intima produce collagen and migrate over the fatty streak forming a FIBROUS PLAQUE

Fibrous Plaque (step 5)

• The fibrous plaque - calcify - protrude into the vessel lumen - obstruct blood flow to distal tissues (especially during exercise), which may cause symptoms (e.g., angina)

• Plaque that has ruptured is called complicated plaque

Complicated lesion (step 6)

• Once plaque ruptures 

• initiates platelet adhesion and activate clotting cascade leading to THROMBUS formation.

• Thrombus may suddenly occlude vessels causing myocardial ischaemia and infarction

Thrombus (step 7)

• Atherosclerosis affects the coronary arteries

• Any vascular disorder that narrows or occludes the coronary arteries

• Atherosclerosis is main cause

• Reduced blood supply to the heart leads to: IHD (Ischaemic heart disease) = CAD (Coronary artery disease)

coronary artery disease

• Release of clotting factors from injured tissue cells & sticky platelets 

• Series of chemical reactions resulting in the formation of thrombin

• Formation of fibrin & trapping of blood cells (RBC and platelets) to form a clot

• Intrinsic (contact activation) 

• Extrinsic (tissue factor)

blood clotting steps 

• breakdown of blood clots

• Converts plasminogen to plasmin by several products of coagulation and inflammation

• Plasmin is an enzyme that dissolves clots (fibrinolysis) by degrading fibrin and fibrinogen into fibrin degradation products 

• Dissolves thrombi in blood vessels 

• A balance between the amounts of thrombin and plasmin in the circulation maintains normal coagulation and lysis

Fibrinolysis

• Injury – plaque rupture

• Platelet adhesion, activation and aggregation - formation platelet plug 

• Activation of clotting

• Fibrin plus platelet plug forms the framework of thrombus

• Fibrinolysis to degrade the thrombus through action of plasmin 

• Uncontrolled thrombus may rupture ‐> embolus

how atherosclerosis causes clotting

• formed in intact blood vessels

• thrombosis - formation of haemostatic plug (blood clot) within blood vessels

thrombus 

• when clot breaks loose and travels through the bloodstream

Thromboembolism

• Myocardial infarction (MI)

• Stroke

• Deep vein thrombosis (DVT)

• Pulmonary embolus

consequences of Thromboembolism

• Adherence of platelets to damaged endothelium

• Activation of platelets 

• Synthesis and release of mediators of platelet aggregation,

• Mediators increase the expression of GP IIb/IIIa receptors

• Promote platelet aggregation

formation of a platelet plug

• pain due to ischemic heart disease 

• reversible 

angina

• heart rate 

• myocardial contraction 

• preload/afterload

• ventricular wall compression

• coronary vessel openness

• diastolic filling time

• balance in myocardial supply and demand

factors that influence the myocardial oxygen balance  

•  increase Heart rate

•  increase Myocardial contractility

•  increase Ventricular wall tension

•  increase Filling pressure (preload)

•  increase Resistance to ejection (afterload)

increased oxgyen demand in angina is due to 

• decrease Coronary blood flow

• decrease Vessel diameter

• increase Heart rate and Ventricular wall tension

decreased oxgyen demand in angina is due to

• Rupture of an unstable plaque within the coronary artery → leads to an occlusive or non‐occlusive thrombus leads to  Acute coronary syndromes (ACS) 

• ACS leads to myocardial infarction (irreversible myocardial damage)

ischaemic heart disease 

• prolonged ischaemia causing irreversible damage to the heart muscle

myocardial infraction 

• Unstable angina

• non‐ST elevation MI (non‐STEMI)

• ST elevation MI (STEMI)

• ST - aspect of ECG

divisions of Acute coronary syndrome

• erodes vessel wall

effect does atherosclerosis have on the development of an aneurysm

• Sudden, severe chest pain – Similar but more severe and prolonged then angina.

• Some individuals, especially those who are elderly or have diabetes, experience no pain.

• Nausea and vomiting

• Transient increase in HR and BP

• Cold clammy skin

• If the patient develops heart failure:

• pulmonary congestion 

• Rales (inspiratory crackles on auscultation) 

• (abnormal heart sound – “third sound”)

signs and symptoms of myocardial infraction

• Determine if there is muscle damage

• Troponin (especially cardiac specific Troponin T or I) 

• CK‐MB (MB isoenzymes of creatine kinase found in heart)

test for MI

• : localised dilation or a protrusion or bulge of a structure of a vessel wall or cardiac chamber

• Area of weakness & vulnerability 

• Formation is due to disruption of vessel wall

• Atherosclerosis is the most common cause of arterial aneurysms

• hypertension increases stress on the wall

• Aorta ‐ susceptible due to constant stress

aneurysm

• Extra vascular haematoma

• More likely to dissect

• only intermost layer if affected

fake aneurysm

• More likely to burst

• affects all the vessel layers

true aneurysm

Stroke = Brain Attack

 IHaemorrhagic stroke • Fatal stroke • Rupture of a blood vessel  bleeding into brain tissue  oedema  brain compression

stroke

• Cause by obstruction of cerebral vessels by thrombosis or emboli 

Ischaemic stroke (more common) 

• Fatal stroke

• Rupture of a blood vessel causes bleeding into brain tissue causing oedema leading to brain compression

 Haemorrhagic stroke

• Decrease in cardiac output

• Insufficient to meet the oxygen demands of the body, which then leads to heart failure.

• Heart not able to maintain cardiac output 

• inadequate perfusion of tissues or, 

• increased diastolic filling pressure of LV 

• increased pulmonary capillary pressures

• classified in stages due to patient response to physical activity

heart failure

• Hyperlipidaemia

• Hypertension

• Diabetes

• Insulin resistance

• High salt intake

• Cardiomyopathy

• Smoking

risk factors of heart failure

• Coronary artery disease

• Hypertension

• Heart valve disease

• Toxic injury (virus, alcohol, drugs etc) 

• Unknown (20%) 

• Rare cases ‐ pregnancy

heart failure causes

• anoxeria

• nausea 

• polyuria

• pain

signs/symptoms of right side heart failure

• HF with reduced Ejection Fraction

• issue with pumping 

• Loss of contractibility of left ventricle 

• Ejection fraction < 40%

• MOST common

• Decreased cardiac output

• enlarge ventricle

systolic heart failure

• HF with preserved Ejection Fraction

• Preserved systolic function leading to  Normal EF

• Pulmonary congestion

• Stiff left ventricle (LV) leads to  lack compliance

• Impaired diastolic relaxation

• LV does not fill appropriately

• weak ventricle muscles - cant push blood out efficenty

diastolic heart failure

• Systolic or diastolic ventricular dysfunction

• Decreased Left ventricle emptying causing increase end distolic volume and Preload increases

• Increased volume and pressure in left ventricle

• Increased volume in pulmonary veins leading to  capillary bed

• Fluid transduction from capillaries to alveoli leading to alveolar space filled fluid

• PULMONARY OEDEMA I

• ncreased pulmonary vascular resistance

• Increased volume and pressure in LA

• right ventricular failure 

left side heart failure 

• Inability of right ventricle to pump causing increased right ventricular afterload

• Can result from Left HF causing increased left ventricular filling pressure cause increase pulmonary capillary pressure causing increase in right ventricular emptying resistance

• In the absence of Left HF, due to hypoxic pulmonary disease, eg COPD

right side heart failure

• Increased pulmonary vascular resistance

• Decreased right ventricle emptying

• Increased volume & pressure in right ventricle and end disatolic & preload increases

• Increased volume and pressure in right atrium
  Increased volume and pressure in the great veins leading to systemic venous circulation

• Increased volume in distensible organs

• Increased systemic capillary pressure

• PERIPHERAL OEDEMA

events of right side heart failure 

• Increased sympathetic nervous system (SNS)

• Renin‐angiotensin‐aldosterone system (RAAS)

• Antidiuretic hormone (ADH) potent vasoconstrictor

• Endothelins potent vasoconstrictor

• Circulatory catecholamines (sympathetic NA and adrenalin)

• Atrial natriuretic peptides (ANPs)  increases diuresis  decreases SNS, RAAS, ADH

Neurohormonal compensation

• Systemic compensation

• Increase the blood volume and redistribution of blood flow

• Increase erythrocytes to  increase oxygen utilisation

systemic compensation

• Increased HR and cardiac contractility 

• Cardiac dilatation leading to Frank Starling mechanism 

• Myocardial hypertrophy and remodelling

Cardiac compensation

• Neurohumoral short term responses  causes the activation of SNS and RAAS and increased release of ADH and NPs

• Net effect causing vasoconstriction (arteries and veins) maintain BP, cardiac stimulation and increased CO

• However long term neurohumoral responses can also worsen HF by increasing ventricular afterload which decreased SV Also by increasing preload this causing pulmonary and systemic congestion 

• Ventricular remodelling may be beneficial short‐term but harmful in long term causing Ventricular wall stiffness

vicious compensatory mechanism

• Preload = Left ventricular end diastolic volume 

• Increased preload

• increase contractility up to a certain extent - Frank Starling mechanism

• However, long‐term increased preload - further impair contractility

• Increased preload  ventricular wall compression  decrease cardiac perfusion  ischaemia  impaired contractility

impact of preload on cardiac function

• normal CO at higher LVED pressures

compensated Heart failure

• with decreased CO with elevated LVED leading to pulmonary congestion

decompensated heart failure

impact of after load on cardiac function 

• Afterload = increased resistance to ejection

• Increase peripheral vascular resistance (PVR) 

• Increased afterload 

• increased ventricular workload

• ventricle hypertrophy

• Ventricular remodelling further impair contractility

• Disturbance of heart rhythm

• Varies in severity

• “Missed” or rapid beats

• Slow HR – bradycardia

• Fast HR – tachycardia

• Serious disturbances  HF and death

arhythmmias

• in hypertension, the left ventricle has to work much harder to eject blood into the aorta against the greater impedance (resistance) in systemic circulation.

• an increase in force is required to eject blood out of left ventricle leading to increased afterload.

• Increased impedence means there is a reduction in amount of blood ejected from left ventricles and hence a reduction in stroke volume.

• This will means there is more left behind - result in an increased end systolic volume will further result in an increase in preload.

• Preload is the volume and pressure/stretch experienced by the ventricle during diastole, prior to contraction and is influenced by factors such as venous return and end systolic volume.

effect of hypertension on afterload and the secondary effect this has on preload

• Increased afterload reduces stroke volume which increases ventricular end-systolic volume

• decrease cardiac output

• increase in afterload will result in a decrease in stroke volume and therefore decreased cardiac output

• heart cant meet the demands of the myocardium

• increase in ventricular workload leading to an increased demand for oxygen. This will further worsen the angina.

• Increased preload will generally result in increased ventricular wall stretch

• increased myocardial workload and demand for blood.

• worsen the mismatch between blood supply through the atherosclerosed vessels and the demand of the myocardium. All these will further aggravate angina.

how hypertension affects the cardiac output

• Hardening of the arteries’ relates to the pathological changes caused by atherosclerosis developing within the walls of arterial vessels.

• Lipids and cells invade the vessel walls rendering them ‘harder’

• cause occlusion of blood flow in focal areas

hardening of blood vessels

• Plaques contain foam cells which are macrophages that phagocytose cholesterol.

• As the plaque grows, the blood vessels narrow, which increases the blood pressure in the vessel. A fibrous cap is formed growth factors to build the plaque to protect the body from plaque contents leaking into the vessel.

• Over time macrophages produce digestive enzymes that damage the fibrous cap, weakening it. When it ruptures, the contents are released into the circulation this leads to thrombosis development platelet factors adhere to fibrous proteins and aggregate to form platelet plug.

rupture in plaque leads to thrombosis development 

• Highly sensitive CRP (hs-CRP) is an acute phase reactant or protein mostly synthesized in the liver and, of the available options, is an indirect measure of atherosclerotic plaque-related inflammation.

laboratory test is an indirect measure of atherosclerotic plaque

• Myocardial ischemia

trigger for angina pectoris

• QRS

complex (wave) represents the sum of all ventricular muscle cell depolarizations

• Aorta

Pressure in the left ventricle must exceed pressure in which structure before the left ventricle can eject blood

increases preload and increases afterload.

systolic heart failure, what effect does the renin-angiotensin-aldosterone system (RAAS) have on stroke volume