Cardio Physiology Flashcards
Where does excitation of the heart usually originate? where is this located in the heart?
sino-atrial node in the right atrium
Describe the ionic basis for the PACEMAKER action potential at the sinoatrial node
- Na+ and K+ influx into the cells (AKA the funny current)
- there is also transient Ca++ influx
this brings the membrane potential up to threshold = action potential in the SA node cells
When the threshold is reached this causes activation of Ca++ channels allowing influx Ca++ = depolarisation
Then there is inactivation of ca++ channels and activation of K+ channels = K+ efflux = repolarisation
How does electrical activity spread:
- from SA to AV node
- From SA node through both atria
- -Within ventricles?
cell-to-cell current flow via gap junctions
What is the role of the AV node?
-only point of electrical contact between atria and ventricles
-cells are small in diameter and have slow conduction velocity
= conduction is delayed to allow atrial systole to precede ventricular systole
How is the action potential spread from the AV node to the ventricles?
Bundle of his and it’s branches and the network of purkinje fibres
Describe the ionic basis for the action potential in atrial and ventricular myocytes?
Cell becomes excited:
Phase 0 - fast Na+ influx (depolarisation)
Phase 1 - closure of Na+ channels and transient K+ efflux
Phase 2 - Mainly Ca++ influx (this happens for a few hundred milliseconds = plateau phase)
Phase 3 - closure of Ca++ and K+ efflux (repolarisation)
Phase 4 - resting membrane potential
How does parasympathetic and sympathetic stimulation affect heart rate?
Parasympathetic stimulation decreases heart rate
Sympathetic increases it
What does vagal tone mean? how does the vagus nerve affect the AV node? Which neurotransmitter is involved and what receptors does this act on?
The VAGUS NERVE (PARASYMPATHETIC supply to the heart) exerts a CONTINOUS influence on the SA node under resting conditions
the VAGAL TONE DOMINATES under NORMAL RESTING CONDITIONS
the VAGAL TONE SLOWS the INTRINSIC HEART RATE from ~100 bpm to produce a NORMAL RESTING HEART RATE of ~70 bpm (it takes longer for the pacemaker cells in the SA node to reach threshold)
Vagus nerve also increases the delay in the AV node
ACh neurotransmitter on muscarinic M2 receptors
What is the sympathetic innervation of the heart? How does sympathetic stimulation affect the heart? What is the neurotransmitter involved and which receptors does this act on?
CARDIAC SYMPATHETIC NERVES supplies SA node and AV node and Myocardium
SYMPATHETIC STIMULATION INCREASES HEART RATE (allows pacemaker cells to reach threshold quicker) and DECREASES AV NODAL DELAY
It also increases the force of contraction
Neurotransmitter is NORADERINALINE acting through B1 adrenoceptors
What does positive and negative chronotropic effect mean?
+ve chronotropic effect = speeds up heart rate
-ve chronotropic effect = slows heart rate
Is cardiac muscle striated? what does this mean? how does excitation spread from one myocyte to the next?
YES - each muscle fibre (AKA myocyte i.e. muscle cells) contains many myofibrils which are the contractile unit of the muscle, these contain actin (thin) and myosin (thick) which slide over eachother in the sliding filament theory (where myosin cross bridges pull actin over myosin via binding sites on actin)
there are no neuromuscular junctions in the heart and excitation is spread via gap junctions
What ion is required to switch on cross bridge formation?
Ca++
How does phase 2 of the action potential in myocytes cause myocyte contraction?
Ca++ influx into cell - this causes calcium induced calcium release from the sarcoplasmic reticulum in the myocyte = activates the contractile machinery = contraction
what does refractory period mean and why is this important for the heart?
REFRACTORY PERIOD: is a period following an action potential in which it is not possible to produce another action potential
During the plateau phase of ventricular action potential the Na+ channels are in the depolarised closed state i.e. they are not available for opening
During the descending phase of action potential the K+ channels are open and the membrane can not be depolarised
The long refractory period is protective for the heart preventing generation of tetanic contractions in the cardiac muscle
What is stroke volume? What is the relation of stroke volume to end diastolic volume and end systolic volume?
Contraction of ventricular muscle ejects the STROKE VOLUME (SV)
This is defined as “the volume of blood ejected by each ventricle per heart beat”
SV = End Diastolic Volume (EDV) – End Systolic Volume (ESV)
How is stroke volume controlled intrinsically?
intrinsically: Changes in STROKE VOLUME are brought about by changes in the end diastolic volume (and changes in the length of muscles fibres in diastole) . (if there is a high EDV, there is a high SV) EDV is determined by cardiac preload (venous return to heart)
What is starlings law of the heart and the frank-starling curve?
The relationship between Venous Return, END DIASTOLIC VOLUME and STROKE VOLUME
It states that “the more the ventricle is filled with blood during diastole (END DIASTOLIC VOLUME), the greater the volume of ejected blood will be during the resulting systolic contraction (STROKE VOLUME)
What is cardiac afterload? how does this affect stroke volume? how does the heart adapt to a high cardiac afterload?
AFTERLOAD means the resistance into which heart is pumping
The extra load is imposed AFTER the heart has contracted
If afterload increases: at first, heart unable to eject full SV, so EDV increases
Force of contraction rises by Frank-Starling mechanism
If increased AFTERLOAD continue to exist (e.g. untreated hypertension), eventually the ventricular muscle mass increases (ventricular hypertrophy) to overcome the resistance
How is stroke volume controlled extrinsically?
This involves NERVES and Hormones
Stimulation of sympathetic nerves INCREASES the FORCE of contraction as it activates more calcium channels mediated via cAMP = positive INOTROPIC effect
Adrenaline and noradrenaline hormones from adrenal medulla have inotropic and chronotropic effect (however these are minor compared with effect of sympathetic nerves)
What is the effect of sympathetic nerve stimulation on the frank-starling curve?
-it shifts the curve to the left: don’t need as much EDV to achieve the same SV
What does a negative inotropic effect change the frank starling curve? what could cause this clinically?
shifts the curve to the right - need more EDV to achieve the same SV.
This happens in heart failure where the contractility of the heart is decreased.
What is cardiac output?
The volume of blood pumped by each ventricle per minute is known as the Cardiac Output (CO)
CO = SV x HR
Do heart valves produce a sound when opening or closing?
closing
What are the 5 events that take place in the cardiac cycle?
1 - passive filling: AV valves open and ventricles fill 80% passively
2 - atrial contraction (P wave on ECG)
3 - isovolumetric ventricular contraction: (After the QRS in ECG) ventricles contract, AV valve pushed shut = first heart sound.
4 - ventricular ejection: intraventricular pressure exceeds pressure in aorta/pulmonary arteries = aortic/pulmonary valve forced open, SV ejected.
5 - isovolumetric ventricular relaxation: (T wave on ECG): Ventricles relax, aortic/pulmonary valves pulled shut = second heart sound. when the ventricular pressure falls below the atrial pressure AV valves pulled open
= new cycle
Why does arterial pressure not fall to zero during diastole?
Arteries recoil to maintain pressure
Which korotkoff sounds are used to record systolic and diastolic BP
1st and 5th
What pressure gradient drives blood around the systemic circulation? how can the pressure be calculated?
pressure gradient between aorta and right atrium:
Pressure gradient = Mean Arterial Pressure (MAP) – Central Venous (right atrial) Pressure (CVP)
What is mean arterial pressure?
Mean Arterial blood Pressure (MAP) is “the average arterial blood pressure during a single cardiac cycle, which involves contraction and relaxation of the heart”
1 way to work this out:
= (2 X diastolic pressure + 1 X systolic pressure) / 3
as diastole lasts 2 times longer than systole in the cardiac cycle
another way to work this out;
MAP can be estimated by adding DBP + 1/3rd of pulse pressure
MAP = DBP + 1/3 difference between SBP and DBP
what is the normal range of MAP, what MAP is needed to perfuse the coronary arteries, brain and kidneys?
70-105 = normal range
At least 60mmHg is needed to perfuse coronary arteries, brain and kidneys
How is MAP related to cardiac output and total peripheral resistance?
Mean Arterial Pressure (MAP) = Cardiac Output (CO) x Total Peripheral Resistance (TPR)
(CO = HR X SV)
What is total peripheral resistance and which blood vessels are the main resistance vessels?
Total Peripheral Resistance is the sum of resistance of all peripheral vasculature in the systemic circulation
Arterioles are the main resistance vessels
How does parasympathetic stimulation affect MAP
-slows heart rate, therefore reduces CO, therefore reduces MAP
How does sympathetic stimulation afftect MAP?
- positive chronotropic and inotropic affect = increases CO
- causes arteriole vasoconstriction = increases total peripheral resistance
- causes vein vasoconstriction = increases venous return = increases SV = increases CO
= increase MAP
Describe the baroreceptor reflex and what does this act to do?
- short term regulation of MAP
baroreceptors in the carotid sinus send signals to the medulla via glossopharyngeal nerve
baroreceptors in the aortic arch send signals to the medulla via vagus nerve
change their firing if there is a change in MAP e.g. standing up
if the MAP DROPS, they fire LESS, parasympathetic stimulation decreases, sympathetic stimulation increases = vasoconstriction/venoconstriction/increased HR
if the MAP RISES, they fire MORE, parasympathetic stimulation increases, sympathetic stimulation decreases = vasodilation
What happens to the baroreceptor reflex if high blood pressure is sustained?
-firing decreases and they re-set to this new normal
what is the main control of MAP in the longer-term?
-blood volume
Relate:
total body fluid
intracellular fluid
extracellular fluid
TBF = ICF + ECF
ICF is usually 2/3 of the total
Relate:
extracellular fluid volume
plasma volume
interstitial fluid volume
ECFV = PV + IFV
What happens to fluid if the plasma volume falls?
compensatory mechanisms shift fluid from IFV to the PV
In a 70kg male how many litres take up plasma, interstitial fluid and intracellular fluid
total body water = 60% body weight = 42 litres
plasma = 3litres interstitial = 11l ECF = 14 litres = 20% body weight
Intracellular fluid = 28 litres = 40% body weight
What are the two main factors that affect extracellular fluid volume?
1: water excess or deficit
2: Na+ excess or deficit
Describe the role of the renin-angiotensin-aldosterone system?
Plays an important role in the regulation of plasma volume and TPR and hence the regulation of MAP
Has three important components (1) Renin (2) Angiotensin (3) Aldosterone
Renin is released from the kidneys and stimulates the formation of angiotensin I in the blood from angiotensinogen (produced by the liver)
Angiotensin I is converted to angiotensin II by Angiotensin converting enzyme - ACE (produced by pulmonary vascular endothelium)
Angiotensin II (1) stimulates the release of Aldosterone from the adrenal cortex (2) Causes systemic vasoconstriction - increases TPR (3) stimulates thirst and (4) ADH release
(Aldosterone (a steroid hormone) acts on the kidneys to increase sodium and water retention – increases plasma volume)
What stimulates renin release?(3) where is it released from?
Renin released from the juxtaglomerular apparatus in the kidney. These include:
(1) Renal artery hypotension -caused by systemic hypotension ( blood pressure)
(2) stimulation of renal sympathetic nerves
(3) Decreased [Na+] in renal tubular fluid – sensed by macula densa (specialised cells of kidney tubules)
What acts as a counter regulator for RAAS?
Atrial natruiuretic peptide:
-released in response to atrial distension and causes:
1: excretion of salt and water in kidneys
2: vasodilation
3: decreases renin release
What is ADH secretion stimulated by? what does it cause?
AKA vasopressin
-Secretion stimulated by (1) reduced extracellular fluid volume or (2) increased extracellular fluid osmolarity (main stimulus)
-causes (1) reabsorption of water in the kidney tubules and (2) vasoconstriction
How is flow related to length of tube and radius of tube?
Flow = L/R to the power 4
what are the extrinsic controls of vascular smooth muscle? what is vasomotor tone?
Nerves:
- sympathetic nerve fibres constrict blood vessels via noradrenaline acting on alpha receptors
- vasomotor tone is that there is always a tonic discharge of sympathetic nerves resulting in continuous release of NA = vessels are partially constricted at rest
Hormones:
- adrenaline from adrenal medulla acting on alpha receptors = vasoconstriction
- adrenaline from adrenal medullar acting on B2 receptors = vasodilation
- Angiotensin 2 = vasoconstriction
- ADH = vasoconstriction
Where are alpha and B2 receptors located?
-B2 receptors: cardiac and skeletal muscle arterioles (they are also in smooth muscle of bronchioles)
-A receptors: skin, gut, and kidney arterioles
= strategic distribution of blood
What is the intrinsic control to relax arteriolar smooth muscle?
Chemical (local metabolites) that relax arteriolar smooth muscle: Decreased local PO2 Increased local PCO2 Increased local [H+] (decreased pH) Increased extra-cellular [K+] Increased osmolality of ECF Adenosine release (from ATP)
Chemical (local humoral agents) that relax arteriolar smooth muscle:
Histamine
Bradykinin
Nitric Oxide (NO) - this is continuously released by endothelial cells of arteries and arterioles
Physical:
- warmth
- stretch: if MAP falls, resistance vessels dilate to regulate blood flow
- sheer stress: Dilatation of arterioles causes sheer stress in the arteries upstream to make them dilate. This increases blood flow to metabolically active tissues
When is nitric oxide released? what does it act as? has it got a long or short half life?
NO is continuously produced by vascular endothelium = potent vasodilator with short half life
Shear stress on vascular endothelium, as a result of increased flow, causes release of calcium in vascular endothelial cells and the subsequent activation of NOS – i.e. flow dependent NO formation
Chemical stimuli can also induce NO formation – receptor stimulated NO formation – many vasoactive substances act through stimulation of NO formation
What is the intrinsic control to cause arteriolar smooth muscle contraction?
Chemicals (humoral agents):
- Serotonin
- Thromboxane A2
- Leukotrienes
- Endothelin - this is a potent vasoconstrictor released from endothelial cells. Its production is stimulated by various agents which cause vasoconstriction
Physical:
- Cold
- stretch: if MAP rises = contract to limit flow
What is the role of endothelium other than an inner lining for blood vessels?
The endothelium is important in maintenance of vascular health
Endothelial damage/dysfunction can be caused by e.g. high blood pressure, high cholesterol, diabetes and smoking
Endothelial produced vasodilators are anti-thrombotic, anti-inflammatory, anti-oxidants
Endothelial produced vasoconstrictors are pro-thrombotic, pro-inflammatory, pro-oxidants
Describe autoregulation of cerebral blood flow?
- if blood pressure rises, vessels constrict to limit blood flow
- if blood pressure falls, vessels dilate to to maintain blood flow
(this is opposite of systemic circulation)
What are the four factors influencing venous return?
- venomotor tone
- blood volume
- skeletal muscle pump
- respiratory pump
What are the 3 intrinsic mechanisms that affect coronary blood flow?
- decrease in P02 cause vasodilation of the coronary arterioles
- metabolic hyperaemia matches flow to demand
- adenosine from ATP is a potent vasodilator
What is the effect of sympathetic stimulation on coronary blood vessels?
- despite alpha receptors being stimulated which act to vasoconstrict the blood vessels this is overridden by:
- circulating adrenaline acting on B2 adrenoceptors to relax vasculature smooth muscle
- sympathetic stimulation increasing heart rate and contractility of the heart via B1 receptors causes a metabolic hyperaemia in coronary blood vessels which causes the coronary vessels to dilate
- sympathetic stimulation
causing an increase in heart rate and contractility = increase in metabolism of heart muscle = inc. in adenosine/metabolites and decrease in P02 = vasodilation
When are the coronary arteries perfused?
diastole
in the brain, what effect does PC02 have on cerebral vasculature?
-increase in PC02 causes cerebral vasodilation
-decrease in PC02 causes cerebral vasoconstriction
= blood flow increases to active parts of brain
describe what can cross the blood brain barrier?
highly permeable to oxygen and carbon dioxide
glucose crosses via faciliated diffusion using specific carrier molecules (brain has an obligatory requirement for glucose)
How does skeletal muscle blood flow change during exercise?
-local metabolic hyperaemia overcomes sympathetic vasoconstrictor activity
-circulating adrenaline acts on B2 receptors = vasodilation
(increase in cardiac output = increases skeletal muscle blood flow many folds)
What is the driving force for fluid flow across capillaries? what kind of fluid can flow across capillary walls?
pressure gradients across the capillary wall
-protein free plasma as it is ‘ultra filtration’
What are the different forces favouring and opposing filtration of fluid across capillaries? what are these forces called?
Favouring:
- capillary hydrostatic pressure (pushes water out)
- interstitial fluid osmotic pressure (pulls water out capillaries) usually minimal
Opposing:
- capillary osmotic pressures (pulls water back in)
- interstitial fluid hydrostatic pressure (pushes water back in) (usually minimal)
how do starling forces affect net filtration pressures at the arteriolar vs venular end of capillary beds?
starling forces favour filtration at the arteriolar end and reabsorption at the venular end
-because capillary hydrostatic pressure is higher at the arteriolar end
During the day does filtration exceed absorption?
Filtration exceeds absorption by 2-4litres and excess fluid is returned to the circulation via lymphatics
What do the starling forces in pulmonary capillaries act to do?
- pulmonary capillary pressure is low and capillary osmotic is high pulling water into the capillaries
- also efficient lymphatic drainage removes any filtered fluid thus preventing accumalation of interstitial fluid
What are the 4 causes of oedema?
1: raised capillary pressure:
- arteriolar dilatation
- raised venous pressure (LVF = pulmonary oedema, RVF = peripheral oedema, prolonged standing = swollen ankles)
2: reduced plasma oncotic pressure (if <30g/l)
- malnutrition
- protein malabsorption
- excessive renal excretion protein
- hepatic failure
3: lymphatic insufficiency:
- lymph node damage
- filariasis (elephantitis)
4: changes in capillary permeability:
- inflammation
- histamine increases leakage of protein
How does heart failure affect the frank-starling curve?
shifts it to the right
-need a higher end diastolic pressure to achieve the same stroke volume
