cardiovascular system

• AREA - area per unit volume is determined by capillary density
• DIFFUSION RESISTANCE - affected by the nature of the molecule, the barrier and the capillary density
• CONCENTRATION GRADIENT - the large the gradient the faster the diffusion rate, to maintain concentration gradient flow must be sufficient
• SUPPLY & DEMAND - increasing metabolism > increased flow this is know as the perfusion rate.

• brain -750 ml/min
• kidney - 1200 ml/min
• heart - 300-1200 ml/min
• skeletal muscle - 1000-16000 ml/min
• skin - 200-2500ml/min
• gut - 1400 -2400ml/min

in total - 5 - 25 l/min

• arterioles - resistance vessels
• veins - capacitance vessels

• elastic to permit recoil > maintaining blood pressure during diastole
• tunica intima: endothelium, narrow subendothelium with discontinuous elastic lamina
• tunica media: 40-70 fenestrated elastic membranes with smooth muscle cells and collagen between lamellae
• tunica adventitia: thin layers of fibroelastic connective tissue containing vasa vasorum, nerves and lymphatics

• tunica intima: endothelium, thick subendothelium - with internal elastic lamina
• tunica media: 40 layers of smooth muscle joined by gap junctions to give co-ordinated contraction
• tunica adventitia: thin layer of firbroelastic connective tissue with some vasa vasorum, nerves and lymphatics

• resistance vessels
• endothelium wrapped in smooth muscle cells
• tunica adventitia is layers of fibroblasts

the smooth muscle is not continuous and instead forms pre-capillary sphincters

• diffusion vessels
• single layer endothelium and basement membrane
• pericytes are a branching outer layer that divide into smooth muscle cells and fibroblasts

• there are three types of capillaries: fenestrated, sinusoids and continuous
• continuous are most common and have tight cell junctions
• fenestrated are found in the gut, endocrine glands and glomerulus
• sinusoids are found in the liver, spleen and bone marrow they allow cells to move between blood and tissue

• post capillary venules are just endothelium and pericytes they are more permeable than capillaries
• venules contain valves and gradually accumulate smooth muscle fibres which are the start of the tunica media

• tunica intima: thin
• tunica media: 2-3 layers of smooth muscle cells
• tunica adventitia: well developed

• capacitance vessels
• thin walls more connective tissue than muscle
• larger diameter then associated arteries
• well developed aadventitia

miss out capillaries

small blood vessels that supply large blood vessels with blood

veins that accompany arteries helping with blood temperature and return to the heart

• swollen enlarged veins
• caused by dysfunctional valves which allow back flow of blood

• inferior middle mediastinum
• between the sternum and the oesophagus

• inextensible sac
• inner serous layer which itself is formed of an inner visceral layer and an outer perital layer - between these layers is a space with a few drops of lubricating fluid

there is then also a outermost fibrous layer

• involuntary
• 3 layers - endocardium, myocardium, epicardium
• low electrical resistance between the cells of the myocardium means they all contract together during systole

found in the SA node control the rate of the heart

• at rest the pacemaker cells in the SA node produce approximately one action potential per second
• this produces a short atrial systole followed by a longer ventricular systole (280ms)
• this is followed by diastole (700 ms)
• in diastole the ventricles relax and the pressure falls causing opening of the AV valves - blood can then flow from the atria into the ventricles throughout diastole
• atrial systole pushes the remaining blood into the ventricles and then about 150 ms the ventricles contract - the rise in pressure forcibly closes the AV valves and once the pressure exceeds the diastolic pressure in the arteries the outflow valves open

• s1 - lup - closure of AV valves at start of ventricular systole
• s2 - dup - closure of outflow valve at the end of systole

• 
• a = atrium contracting tricuspid valve open
• c = small back flow into atrium as ventricle contracts
• x = atrium relaxing then filling
• v = atrium tense and full
• y = tricuspid valve open

• RA = 0-8mmHg
• LA = 1-10 mmHg
• RV = 15-30/0-8
• LV = 100-140/1-10
• pulmonary artery = 15-30/4-12
• aorta = 100-140/60-90

• anterior left ventricle
• some right ventricle
• intraventricular septum

• posteriorlateral left ventricle
• left atrium

• right atrium
• AV & SA nodes

• apex
• intraventricular septum

Cephalocaudal folding brings heart into chest region

Lateral folding creates primative heart tube from fusion of endocardial tubes - this tube is suspended in a cavity by a membrane that degenerates

The tube receives blood supply from the caudal pole and begins to pump blood around the first aortic arch into the dorsal aorta

• The tube continuous to elongate and on day 23 looping begins - (cephalic portion bends ventrally,
• caudally and to the right AND caudal portion bends dorsally, cranially and to the left)

This creates the cardiac loop by day 28

• Looping occurs so that the primordium of the RV is by the outflow tract and the primordium of the LV is by the inflow tract and the atrium is dorsal to the bulbus
• cortis

After looping the atrium and ventricle communicate by the atrioventricular canal

The L and R horns are equal in size but venous return switches to the R – L reseeds and R horn is absorbed enlarging the atria

The RA develops from the sinous venosus and the primordial atrium. The LA develops from a small part of the primitive atrium and the proximal part of the pulmonary vessels

Once looping has occurred we need septation to have two pumps in series

Septation of the atrioventricular canal – growth of endocardial cushins

Atrial septation – septum primum grows down towards endocardial cushins, the gap is called the ostium primum, before it closes apoptosis forms the ostium secundum to replace it. The septum secundum then grows up leaving a crescent shape whole at the bottom called the foramen ovale (fossa ovalis after birth)

Ventricular septation – the muscular septum grows up forming most of the septum the membranous septum is made of CT and grows down from the cushins

Septation of the outflow tract – endocarcial cushins form in the truncus arteriosus as the grow they twist around each other forming a spiral septum

• lungs are non functional
• oxygenated blood come via the placenta from the mother
• blood comes via liver > RA > LA > LV > body
• some blood goes into the RV so the muscle can develop but it by-passes the lungs using the ductus arteriosus
• at birth the ductus arteriosus, RtoL shunt and the ductus venosus must all close

• ASD - osteum secundum defect/patent foramen ovale/ primum atrial defect > increase pulmonary blood flow > RV volume overload > right heart failure - fixed splitting of s2
• obstructive lesions - aortic/pulmonary stenosis > split s1+systolic murmor, coarctation of the aorta > radial femoral delay, mitral stenosis > loud s1
• VSD - LtoR shunt > pulmonary venous congestion > pulmonary hypertension
• PDA - lack of prostaglandins from mother and bradykinins from lungs means DA fails to close > heart failure, continuous murmor

• complex LtoR shunts
• transposition of the great arteries - this is only viable with patent ductus arteriosus or AV shunt
• tetralogy of fallot = pulmonary stenosis + VSD + RV hypertrophy + over-riding aorta

• contraction of vascular and visceral smooth muscle
• some endocrine and exocrine secretions
• force and rate of heart contraction

SYPATHETIC - post ganglionic cardiac nerve from the sympathetic trunk innervates the SA & AV nodes and the myocardium . release of NA acts on B1 receptors inc. HR and force of contraction (in cAMP > phosphorylation of Ca channels > inc Ca entry > inc force of contraction) + increases slope of pacemaker potential

PARASYMPATHETIC - 10th cranial nerve/vagus nerve synapses in wall of the heart with SA and AV nodes the post ganglionic cells release ACh with acts on M2 receptors > dec HR (-ve chronotrophic) and dec AV node conduction velocity. it also slows pacemaker potential by opening K channels via cAMP.

• most vessels = sympathetic innervation, A1 receptors sympathetic output normal = vasomotor tone, dec = dilation, inc = constriction
• cardiac muscle, skeletal muscle, liver = sympathetic innervation A1and B2 receptors - circulating adrenaline has higher affinity for B2 receptors > vasodilation

sypathomimetics: adrenaline (cardiac arrest & anaphylactic shock), dobutamine (B1 agonist - give in cardiogenic shock), salbutamol (B2 agonist -asthma)

adrenoceptor agonists: prazosin (A1 antagonist - inhibit NA action on smooth muscle - treat hypertension), atenolol (B1 antagonist - slow HR and reduce force of contraction)

cholinergics: pilocarpine (muscarinic agonist - treat glucoma), atropine (muscarinic agonist - inc HR, cause bronchiodilation - dilate pupils for eye exam)

• s: NA acts on A1 receptor > pupil dilates
• p: ACh acts on M3 receptor > pupil constricts

• s: NA acts on A1 receptors > thick viscous secretion > dry mouth
• p: ACh acts on M3 receptor > watery mucus high enzyme content

• s: circulating adrenaline acts on B2 receptors > dilation
• p: ACh acts on M3 receptors > constriction

• s: NA acts on B1 receptors > inc firing > inc HR
• p: ACh acts on M2 rceptors > reduced firing > reduced HR

• s: NA acts on B1 receptors > inc contractile force
• p: ACh acts on M2 rceptors > reduced contractile force

s: NA acts on B1 receptors > inc contractile force

s: NA acts on A1 receptors > constriction

s: NA acts on B2 receptors > dilation

• s: NA acts on A1 receptors > constriction of blood vessels
• p: ACh acts on M3 receptors > dilation of BVs > erection

s: NA acts on A1/2 receptors > ejaculation

s: NA acts on A1 & B1 receptors > lipolysis

s: NA acts on A1/2 & B2 receptors > glycogenolysis

s: NA acts on A1 receptor > salt and water retention

s: ACh acts on M3 receptors > secretion

s: NA acts on A2 & B2 receptors > constriction of sphincters, NA act on all receptor > decreased motility

p: ACh acts on M3 receptors > inc motilty , inc secretion and relaxation of sphincters

• the volume of blood passing a given point per unit time
• Q= P/R

• the rate of movement of fluid particles along the tune
• V = Q/area
• V is proportional to 1/SA

• LAMINAR - high central velocity
• TURBULENT - flow resistance greatly increased - hear bruit

the property of a fluid that resists the force tending to cause the fluid to flow, the higher the viscosity the lower the velocity

resistance is proportional to rxrxrxr

reduces the resistance of the capillaries as there are so many in parallel

• as the vessel stretches the resistance falls
• as the pressure drops the vessel collapses causing a cease in blood flow before the pressure reaches zero

arteries stretch during systole and recoil during diastole maintaining an even pressure

if the walls were rigid then pressure would be very high in systole and zero in diastole

if the circulation to a part of the body is cut off for a short amount of time when blood flow is restored there is a massive increase in to this area for a short amount of time while metabolites (H, K, adenosine) which cause vasodilatation are washed away once they are washed away the SM of the BV can constrict again

• if supply pressure changes the flow to the tissue changes
• this alters metabolite concentration
• this alters arteriole resistance
• thus correct blood flow to the tissue is maintained

• arterial pressure DOWN
• venous pressure UP

• arterial pressure UP
• venous pressure DOWN

• arterial pressure UP
• venous pressure DOWN

• arterial pressure DOWN
• venous pressure UP

CO = STROKE VOLUME X HEART RATE

• ventricular filling: starlings law more in = more out
• force of contraction - can be increased by sympathetic activity
• HR

• stretched muscle contracts harder so if more blood is put into the heart by high venous pressure the harder it will contract and the higher the stroke volume will be
• 

• vasodilation around the gut
• fall in TPR
• rise in venous pressure therefore fall in arterial pressure
• the high venous pressure > increase in CO - Starlings law
• low arterial pressure triggers SNS > Inc HR
• demand met

• if HR increases initially with no other change
• venous pressure falls
• so SV falls
• so CO is normalised
• - the heart is controlled by the circulation

• massive increase in demand and muscle pumping > inc venous return
• the increase in venous pressure is a problem as it tends to overfill the heart
• overfilling is prevented by a rise in heart rate as soon as exercise begins from the brain

• blood pools in superficial leg veins
• central venous pressure falls
• so starlings law causes CO to fall
• - this doesn't work because both arterial and venous pressure have changed in the same direction
• SPECIAL MECHANISM - baroreceptors increase HR as venous pressure falls and TPR increases by minimising perfusion to the skin and gut this defends the arterial pressure

failure of this = postural hypotension

• reduced blood volume > low venous pressure > low CO >low arterial pressure
• baroreceptors detect and increase HR and TPR
• this helps arterial pressure but further lowers venous pressure
• to raise venous pressure the vessels constrict and fluid moves from extracellular into circulation

• blood volume is controlled by the kidney
• if blood vol is increased for days
• venous pressure increases
• CO increases
• arterial pressure increases
• TPR increases > further rises in arterial pressure > high BP

• heart rate is dependant upon the ANS
• baroreceptors in the carotid sinus and aortic arch detect stretch and send messages to the medulla

bainbridge reflex = if venous pressure rises HR rises

• 
• in diastole the cell membrane potential is most permeable to K so the membrane potential is close to Ek at around -80mV
• spread of activity raises the cells to threshold by an initial depolarisation this opens voltage gated Na channels so equilibrium moves towards Ena
• Na channels are quickly inactivated but by this point the Ca channels are open
• Ca channels cause a large influx of Ca causing contraction they remain open for the rest of systole and when they close K channels open

• 
• pacemaker cells are normally found in the SA node
• the spontaneously generate APs
• the dont have fast Na channels so the upward stroke is dependant on Ca channels that also close quickly
• they have a feature called pacemaker potential - the membrane depolarises at a steady rate until it reaches threshold - HR is dependant on the steepness of the pacemaker potential

• arrhythmias can be tachycardia, bradycardia, atria flutter, atrial fibrillation, ventricular fibrillation
• they can be caused by: ectopic pacemaker activity due to a damaged area of myocardium,
• 4 classes of dugs:
• 1. voltage dependant Na channel blockers - lidocaine - prevents after depolarisations but allows normal HR used after MI if patient shows signs of ventricular tachycardia to prevent VF
• 2. B blockers - atenalol - blocks SNS acting on B1 receptors in the heart > decrease slope of pacemaker potential > dec HR - used after MI to prevent VF reduces O2 requirement of the heart, can also be used to treat slow conductance of the AV node or used in hyperthyroid to reduce affects on the heart
• 3. K channel blockers - prolong AP by lengthening ARP - used to treat tachycardia associated with Wolff-Parkinson-White syndrome
• 4. Ca channel blockers - dec slope of pacemaker potential, dec AVN conductance, dec force of contraction, cause coronary and peripheral vasodilation

• the idea is the reduce the force of contraction, reduce CO, reduce tissue perfusion and oedoma
• 1. cardiac glycosides - digoxin - block Na/K-ATPase causing a rise in intracellular Na this reduces the effect of NCX and thus more Ca is stored in the SR +ve inotrphic affect and also reduce HR
• 2. ACE inhibitors
• 3. diuretics
• 4. B blocker

• reduce workload of the heart - B blockers, Ca channel antagonists, organic nitrates
• improve blood supply to the heart - organic nitrates, Ca channel antagonists

• diuretics
• ACE inhibitors
• B blockers
• Ca channels antagonists
• A1 adrenoceptor antagonists

• used in AF, acute MI, mechanical valves
• heparin - inhibits thrombin
• warfrin - antagonises vit K
• asprin - anti platelet

• RA-On the right arm, avoiding thick muscle.
• LA-In the same location that RA was placed, but on the left arm this time.
• RL-On the right leg, lateral calf muscle
• LL-In the same location that RL was placed, but on the left leg this time.
• V1-In the fourth intercostal space (between ribs 4 & 5) just to the right of the sternum (breastbone).
• V2-In the fourth intercostal space (between ribs 4 & 5) just to the left of the sternum.
• V3-Between leads V2 and V4.
• V4-In the fifth intercostal space (between ribs 5 & 6) in the mid-clavicular line (the imaginary line that extends down from the midpoint of the clavicle (collarbone)).
• V5-Horizontally even with V4, but in the anterior axillary line. (The anterior axillary line is the imaginary line that runs down from the point midway between the middle of the clavicle and the lateral end of the clavicle; the lateral end of the collarbone is the end closer to the arm.)
• V6-Horizontally even with V4 and V5 in the midaxillary line. (The midaxillary line is the imaginary line that extends down from the middle of the patient's armpit.)
• 

• rate
• rhythmn
• axis
• p wave
• qrs complex
• pr interval
• st segment
• t wave
• 

• a) st elevation
• b) inverted t waves
• c) pathological q waves

• not itself a problem but may indicate CAD, electrolyte disturbance ...
• prolonged PR interval

• some atrial impulses not conducted to the ventricles
• 3 types
• mobitz type 1: progressive lengthening of PR intervals and then a failed conduction
• mobitz type 2: most beats are conducted but occasional missing QRS complex
• 2:1, 3:1... more P waves than QRS complexes

• no conduction from atria to ventricles can be caused by MI or fibrosis of bundle of His pacemaker required
• no relationship between P and QRS
• abnormal QRS

bundle branch block no conduction is carried down right side but left is as usual causes a M in lead v1 and a W in lead v6

may indicate atrial septal defect

• v1 = W
• v6 = M
• may also be t wave inversion

may indicate aortic stenosis, ischaemic disease or possibly an MI

multiple P waves for each QRS complex

• abnormal random QRS can be any shape
• if occur early in t wave of a proceeding beat can lead to VF

• atrial muscle contracts independantly of the SA node
• no p waves
• irregular base line
• irregular QRS
• normal shaped QRS

• muscle fibres contract independantly
• no pattern

• the lung have two circulations
• the bronchial circulation - part of the systemic and the pulmonary circulation
• the pulmonary circulation works with low resistance and low pressures
• low resistance is due to short wide vessels lots of capillaries and little smooth muscle in the arterioles
• hypoxic pulmonary vasoconstriction ensures ventilation perfusion matching

• rigid cranium doesn't allow for volume expansion
• increases in intercranial pressure impair intercranial bloodflow
• impaired blood flow to vasomotor control regions of the brain stem increase sympathetic activity
• increases arterial pressure
• helps maintain cerebral blood flow

• brain receives 20% of CO
• meets o2 need by having high density capillaries, short diffusion distance, high basal flow rate and high o2 extraction rate
• neurones are very sensitive to hypoxia

• arise from aortic sinuses
• blood flow is mainly in diastole
• capillary density is high
• capillaries produce lots of O/NO to dilate vessels
• there are few anastomoses
• prone to atheroma

• must be able to increase o2 delivery and nutrient delivery and remove metabolites
• it has a role in regulating arterial BP
• resistance vessels have strong sympathetic innervation
• cap density depends on muscle type postural muscle have very high density
• vasodilators = adenosine K and H

• Main function = body temp regulation
• acral/apical skin has specialised structures called atereovenous anastomoses
• apical skin has a high SA to volume volume ratio
• under neural control
• inc sympathetic tone of AVAs reduce blood flow to apical skin raise core body temp

heart fails to maintain adequate circulation for the needs of the body despite adequate filling pressures

• primary cause is ischaemic heart disease
• other causes = hypertension, dilated cardiomyopathy - bugs drugs and pregnancy, valvular heart disease, pericardial disease, arrhythmias

NYHA class 1-4

• right sided heart failure
• left sided heart failure
• congestive heart failure
• systolic HF- pump failure
• diastolic HF - failure of relaxation

• fatigue
• exertional dyspnoea
• orthopnea
• paroxysmal nocturnal dyspnoea
• tachycardia
• cardiomegaly
• mitral regurge
• peripheral oedema
• basal pulmonary crackles

• most common is secondary to LHF
• others = chronic lung disease, PE, pulmonary hypertension, tricuspid valve disease
• LtoRshunts
• isolated right ventricular cardiomyopathy

• fatigue
• dyspnoea
• anorexia
• nausea
• raised JVP
• tender smooth hepatic enlargement
• oedema
• ascites
• pleural effusion

• lifestyle modifactions
• diuretics
• ACE inhibitors
• nitrates
• B blockers
• anti-arrhythmias
• surgery

• CO = 5l/min
• SV = 75 ml
• LV end systolic vol = 75 ml
• LV end diastolic vol = 150 ml
• ejection fraction = > 50 %

• inc LV capacity
• reduced LV CO
• thinning of myocardium
• mitral valve incompetence
• neuro-hormonal activation
• cardiac arrhythmias

• loss of muscle
• unco-ordinated abnormal contraction
• changes in ECM - increase in type iii collagen, slippage of myocardial fibre orientation
• changes in cellular structure and function

• SNS - early compensation to improve CO > damage
• RAAS - activated by poor kidney perfusion or SNS > elevated angiotension II > LV hypertrophy, myocyte dysfunction and worsens hypertension
• NATRIURETIC HORMONES - balance effects of RAAS on vascular tone
• ADH - inc water retention > inc co > inc stress on walls

• this is normally in elderly females with a history of hypertension/obesity/diabetes
• normal LV function but concentric LVH
• impaired relaxation of heart > impaired LV filling > raised PA pressure > low CO > triggers neuro-hormonal response

• angina
• MI
• pericarditis
• aortic dissection
• aortic aneurysm
• PE
• infection
• reflux
• peptic ulcer
• cervical disc degeneration

characterised by lack of oxygen to heart muscle causing ischaemia main reason is CAD

• caused by atherosclerlosis
• starts with fatty streak > foam cells + smooth muscle cells > plaque
• risk factors = age, male, family history, high cholesterol . low HDLs, hypertension, smoking, diabetes, LVhypertrophy, obesity, alcohol

• this is a symptom
• often caused by CAD
• exercise stress test may show ST elevation

• no necrosis
• plaque rupture
• > 90 % occulsion

• MI necrosis secondary to interuption of blood supply
• full occulsion
• complications - arrhythmias, LV failure, cardiogenic shock,

• creatine kinase MB
• troponin 1
• released by dead myocytes

• thrombolysis and angioplasty
• asprin
• Bblockers
• anti coagulants

• acute condition of inadequate blood flow throughout the whole body
• can be due to a fall in TPR or CO

• TPR - anaphylaxis/sepsis > distributive shock
• CO -
• - haemorrhage/burns > hypovolaemic shock
• - MI/ heart failure > cardiogenic shock
• - cardiac tamponade/PE > mechanical shock

• distributive > tachycardia, warm red extremities, strong pulse
• other > tachycardia, weak pulse, cold and clamy extremities

• unresponsive
• lack of pulse
• can be asytole or VF
• correction by defibrilation and give adrenaline