Physiology Flashcards
Excitation of the heart normally originates in?
Pacemaker cells in the SA node
Where is the SA node located?
The upper right atrium close to where the Superior Vena Cava enters the right atrium.
A heart controlled by the sino-atrial node is said to be….
in sinus rhythm
Explain why potential is generated in the SA node
The cells in the SA node have no stable resting membrane potential.
The cells in the SA node generate regular spontaneous pacemaker potentials.
The spontaneous pacemaker potential takes the membrane potential to a threshold
Every time the threshold is reached an action potential is generated
This results in the generation of regular spontaneous action potentials in the SA nodal cells
How is the potential generated in the SA node spontaneous
In the pacemaker cells the permeability to K+ does not remain constant between action potentials
The pacemaker potential (i.e. the slow depolarisation of membrane potential to a threshold) is due to:
Decrease in K+ efflux
Na+ and K+ influx (the funny current)
Transient Ca++ influx (T-type Ca++ channels)
Once the threshold is reached the rising phase is caused by:
Activation of long lasting (L-TYPE Ca++ CHANNELS) resulting in Ca++ influx
The falling phase is caused by:
Inactivation of L-type Ca++ channels and
Activation of K+ channels resulting in K+ efflux
Explain how excitation spreads in the heart
Originates in SA node, spreads by cell to cell conduction to atrioventricular node.
From AV node impulse passes by special pathway through bundle of His.
This has left and right ventricles, passes through purkinje fibres.
The Bundle of His and its branches and the network of Purkinje fibers allow rapid spread of action potential to the ventricles
Excitation of the ventricles spreads by cell to cell conduction again.
How does cell to cell conduction work?
Flows by gap junctions
Purpose of the AV node
The AV node is the only point of electrical contact between atria and ventricles
The AV node cells are small in diameter and has slow conduction velocity
This allows atria to complete contraction before the ventricles contract.
Where is the AV node located?
The base of the right atrium; just above the junction of atria and ventricles
Explain the plateau phase of action potential
The membrane potential is maintained near the peak of action potential for few hundred milliseconds
This is called the plateau phase of action potential
It is a unique characteristic of contractile cardiac muscle cells
The plateau phase is mainly due to influx of Ca++ through L-type Ca++ channels
The heart rate is mainly influenced by the _________
Sympathetic stimulation _____the heart rate
Parasympathetic stimulation _____ the heart rate
ANS
increases
decreases
Under resting conditions what does the vagus nerve do?
Exerts a continuous influence on the SA node. Vagus nerve supplies both the SA and the AV node. Vagal tone dominates under resting conditions. Vagal tone slows the intrinsic heart rate from ~100 bpm to produce a normal resting heart rate of ~70 bpm
Normal resting heart rate is usually
60-100bpm
Define bradycardia and tachycardia
Bradycardia= resting heart rate under 60bpm Tachycardia= resting heart rate more than 100bpm
Vagal stimulation ____1____ heart rate and ______2____ AV nodal delay (_____3___ the slope of pacemaker potential)
Neurotransmitter is ____4___ acting through _______5____ Receptors
Vagus exerts a _______6_____ effect on heart (decreases heart rate)
1 slows 2 increases 3 decreases 4 acetylcholine 5 muscarinic M2 receptors 6 negative chronotropic effect
Cardiac sympathetic nerves supplies ______1_____
Sympathetic stimulation ____2____ heart rate and ____3____ AV nodal delay.
Neurotransmitter is _____4____
1 SA node and AV node and myocardium
2 increases
3 decreases
4 noradrenaline acting through B1 adrenoceptors
Positive inotropes?
Negative inotropes?
Positive inotropes increase contractility
Negative inotropes decrease contractility
Normally heart valves produce a sound when they __1___, but normally not when they ___2___
1 shut
2 open
5 stages of the cardiac cycle?
1 Passive filling 2 Atrial contraction 3 Isovolumetric ventricular contraction 4 Ventricular ejection 5 Isovolumetric ventricular relaxation
Describe passive filling
- Pressure in atria and ventricles close to zero
- AV valves open so venous return flows into the ventricles
- Aortic pressure ~ 80 mmHg, and aortic valve is closed
- Similar events happen in the right side of the heart, but the pressures (right ventricular and pulmonary artery) are much lower
- Ventricles become ~ 80% full by passive filling
Describe atrial contraction
Atria contract to fill the rest of the ventricles
Describe Isovolumetric ventricular Contraction
Ventricles contract
Ventricular pressure rises
When the ventricular pressure exceeds atrial pressure the AV valves shut
This produces the first heart sound (LUB)
The aortic valve is still shut, so no blood can enter or leave the ventricle
Describe ventricular ejection
When the ventricular pressure exceeds aorta/pulmonary artery pressure the Aortic/pulmonary valves open. The SV is ejected by each ventricle leaving behind the ESV. Aortic Pressure rises. There will be ventricular depolarisation. The ventricles relax and the ventricular pressure start to fall. When the ventricular pressure falls below aortic/pulmonary pressure: aortic/pulmonary valves shut. This produces the second heart sound (DUB)
Describe isovolumetric ventricular relaxation
Closure of aortic/and pulmonary valves signals the start of the isovolumetric ventricular relaxation
As the ventricles are shut the tension falls around a closed volume. When the ventricular pressure falls below atrial pressure, AV valves open and the heart starts a new cycle.
The first heart sound (S1) is caused by closure of_____1_______. It sounds like a “lub”
• S1 heralds the beginning of _____2___
• The second heart sound (S2) is caused by closure of ____3____. It sounds like a “dub”
• S2 heralds the end of systole and the beginning of ___4____
1 mitral and tricuspid valves
2 systole
3 aortic and pulmonary valves
4 diastole
What is the all or none law of the heart?
Electrical excitation always spreads to all the cardiac myocytes.
What do desmosomes do?
- The Desmosomes within the intercalated discs provide mechanical adhesion between adjacent cardiac cells.
- They ensure that the tension developed by one cell is transmitted to the next.
Describe the role of calcium in excitation contraction coupling
- Ca2+ is released from the sarcoplasmic reticulum (SR)
- Calcium needs to enter the cell to trigger the release of more calcium from the sarcoplasmic reticulum.
- Calcium in plateau phase results in more calcium being released from SR
- Intracellular calcium rise results in enough calcium to activate contractile machinery
- Once the action potential is generated calcium is actively pumped back out into the SR.
What is the purpose the long refractory for the heart?
Protection against excessive heart rate
Define stroke volume
Stroke volume= the volume of blood ejected by each ventricle per heart beat= end diastolic volume- end systolic volume= blood ejected by contraction of ventricular muscle
What is Frank Starling Mechanism/ Starling’s Law of the Heart?
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)
Define cardiac preload and after load
- Preload= how much ventricular muscle is stretched with blood, how much blood is in the heart before contraction.
- Afterload= afterload means the resistance into which heart is pumping. The extra load is imposed after the heart has contracted.
- Sympathetic stimulation shifts the Frank starling curve to the ___1____
- Heart failure shifts the curve to the ___2___
1 left
2 right
Define cardiac output
The volume of blood pumped by each ventricle per minute= SV x HR= 5l per minute.
Explain phase 4 of the fast response
Resting membrane potential Outward flux of K+ is dominant IK1 potassium channels Small inwards leak of sodium Ion concentration gradients maintained by Na/K ATPase
Explain phase 0 of the fast response
The upstroke
Fast inward flux of sodium ions
Sodium potential is not reached cause channels open quickly but then quickly go into non-conducting state
Explain phase 1 of the fast response
Early repolarisation
Outward flux of K+ is dominant
Ito potassium channels for transient efflux
Na+ channels are inactive
Explain phase 2 of the fast response
This is the plateau
Inward flux of Ca2+ is roughly balanced by outward flux of K+
Ca2+ channels are Ical
Calcium coming into the cell at this point causes release of calcium from the sarcoplasmic reticulum (calcium induced calcium release)
Ca2+ is depolarising but K+ is hyperpolarising
Plateau exists for as long as the balance remains
Explain phase 3 of the fast response
This commences at the end of phase 2 when outward K+ currents exceed inwards Ica
During the plateau Ical slowly decrease due to inactivation of L-type channels whereas Ikr and Its slowly activate in succession
3 different K+ currents contribute to repolarisation.
Mechanism for which sympathetic stimulation can increase cardiac rate and force?
Noradrenaline activates beta 1 receptors these are GCPRs and intracellular concentrations of cyclic AMP are increased resulting in increased funny current.
Sympathetic stimulation causes increased conduction velocity in the AV node which is a
positive dromotropic effect
Sympathetic stimulation decreases systole due to… this is a ….
due to increased uptake of Ca2+ into the sarcoplasmic reticulum
positive lusitropic action
M2 receptors coupling through Gi protein results in….
inhibition of adenylyl cyclase and reduces cAMP and opens potassium channels in the SA node.
Define blood pressure
The outwards pressure (hydrostatic) exerted by the blood on blood vessel walls.
What is hypertension defined as?
Clinic blood pressure of 140/90 mmHg or higher and day time average of 135/85 mmHg or higher.
Define pulse pressure and what it usually is
The difference between systolic and diastolic blood pressures. Normally between 30 and 50.
Define Mean Arterial Blood Pressure
The average arterial blood pressure during a single cardiac cycle, which involves contraction and relaxation of the heart.
Define Systemic Vascular Resistance
The sum of resistance of all vasculature in the systemic circulation.
What is the minimum MAP required to perfuse the brain, heart and kidneys?
60 mmHg
What are acute changes in blood pressure controlled by?
Baroreceptor reflex
Where is the cardiovascular control centre?
The medulla of the brainstem
What process happens if there is reduced blood pressure?
Reduction in blood pressure will result in a decrease in the number of afferent impulses from the baroreceptors. The sympathetic activity will increase and as a result, the SVR, HR and the stroke volume will all increase. Decrease in vagal activity (parasympathetic nerve). All these changes will result in increasing the blood pressure back to normal.
What happens if there is increased blood pressure?
This happens in situations like exercise or stress. Increased blood pressure will result in stretching of the stretch receptors. This increases the frequency of afferent impulses. Increase in vagal activity (parasympathetic nerve). Stroke volume and heart rate decrease. Finally, the blood pressure is decreased back to normal.
What are the major resistance vessels?
Arterioles
Where are baroreceptors located
In the carotid sinus and arch of the aorta
When may the baroreceptor reflex be important?
When someone stands up suddenly
Explain postural hypotension
- Postural Hypotension= Failure of Baroreceptor responses to gravitational shifts in blood, when moving from horizontal to vertical position
- Risk factors= age related, medications, certain diseases, reduced intravascular volume and prolonged bed rest
- A positive result is indicated by a drop, within 3 minutes of standing from lying position: in systolic blood pressure of at least 20 mmHg (with or without symptoms) or a drop in diastolic blood pressure of at least 10 mm Hg (with symptoms)
- Symptoms may include those of cerebral hypoperfusion such as: lightheadedness, dizziness, blurred vision, faintness and falls
Explain why baroreceptors only regulate blood pressure short term
- Baroreceptors firing decreases if high blood pressure is sustained
- Baroreceptors “re-set” - they will fire again only if there is an acute change in MAP above the new higher steady state level
- Therefore, the Baroreceptors cannot supply information about prevailing steady state blood pressure
How is long term blood pressure controlled?
Regulation of extracellular fluid as if plasma volume falls fluid would be shifted into the plasma from the ECF and increasing or decreasing blood volume will affect blood pressure (starlings law) as stroke volume and heart rate will decrease or increase accordingly
Three hormone systems that help regulate ECF
- The Renin-Angiotensin- Aldosterone System – RAAS
- Natriuretic Peptides – NPs
- Antidiuretic Hormone (Arginine Vasopressin) - ADH
Renin-angiotensin-aldosterone system increases or decreases blood pressure
increases blood pressure
What are the three components of the RAAS
Three components renin, angiotensin and aldosterone
What is initially released from the kidneys in RAAS and what does it stimulate formation of?
Renin stimulates angiotensin
3 things angiotensin does in RAAS
Angiotensin stimulates the release of Aldosterone from the adrenal cortex. Causes systemic vasoconstriction - increases SVR. It also stimulates thirst and ADH release
What does aldosterone do in RAAS?
Acts on the kidneys to increase sodium and water retention – increases plasma volume
What stimulates renin/ switches on RAAS?
- Renal artery hypotension -caused by systemic hypotension ( decreased blood pressure)
- Stimulation of renal sympathetic nerves
- Decreased [Na+] in renal tubular fluid – sensed by macula densa (specialised cells of kidney tubules)
Describe the role of NPs (Natriuretic peptides)
- Released in response to cardiac distension or neurohormonal stimuli
- They cause excretion of salt and water in the kidneys, thereby reducing blood volume and blood pressure
- Decrease renin release - decrease blood pressure
- Act as a vasodilators - decrease SVR and blood pressure
- NPs provide a counter-regulatory system for the Renin-Angiotensin-Aldosterone System (RAAS)
Describe the role of ADH in control of blood pressure
- ADH acts in the kidney tubules to increase the reabsorption of water (conserve water) - i.e. concentrate urine (antidiuresis)
- This would increase extracellular and plasma volume and hence cardiac output and blood pressure
- ADH (vasopressin) also acts on blood vessels to cause vasoconstriction - increase SVR and blood pressure: the effect is small in normal people but becomes important in hypovolaemic shock (e.g. haemorrhage)
What contains most of the blood volume under resting conditions?
The veins
What factors can influence stroke volume?
Pre-load/myocardial contractility/after-load
Main site of systemic vascular resistance is…
The arterioles
- Usually blood viscosity and length remains _____1_____ so to change SVR ____2____ is used.
- You can change the flow a lot by varying the radius a ___3___ amount.
1 fairly constant
2 radius
3 small
- The vascular smooth muscles are supplied by _____1_____ nerve fibres. The neurotransmitter is ____2_____ acting on alpha receptors
- They are partially constricted at rest. This is called the ____3____ tone.
- The vasomotor tone is caused by ______________4________________
1 sympathetic
2 noradrenaline
3 vasomotor
4 tonic discharge of sympathetic nerves resulting in continuous release of noradrenaline
- Adrenaline is released from the ____1______
- Effect of adrenaline is largely organ specific. It depends on the predominant type of receptor
- Adrenaline acting on alpha receptors causes ___2___
- Adrenaline acting on beta 2 receptors causes _____3_____
- alpha receptors are predominant ______4______
- beta 2 receptors are predominant _____5____
- This helps with strategic redistribution of blood e.g. during exercise
1 the adrenal medulla 2 vasoconstriction 3 vasodilation 4 in skin, gut, kidney arterioles 5 in cardiac and skeletal muscle arterioles
Chemical factors that can stimulate vasodilation?
Metabolic hyperaemia
histamine, bradykinin and NO (in inflammation)
2 mechanisms that result in NO formation?
- Sheer 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
Chemical factors that can stimulate vasoconstriction?
Serotonin, Thromboxane A2 and Leukotrienes and Endothelin
Physical factors that can cause vasoconstriction and vasodilation?
- Temperature
- Myogenic response to Stretch: If MAP rises resistance vessels automatically constrict to limit flow. If MAP falls resistance vessels automatically dilate to increase flow. This is important in tissues like brain and kidneys
- Sheer stress: Dilatation of arterioles causes sheer stress in the arteries upstream to make them dilate. This increases blood flow to metabolically active tissues
5 factors that influence venous return?
- Increased venomotor tone (pushes blood from veins to heart)
- Increased blood volume (more blood overall obviously more blood returns to the heart)
- Increased skeletal muscle pump
- Increased respiratory pump
- Increased atrial pressure
Describe how the respiratory pump works in terms of venous return
- During inspiration, intrathoracic pressure decreases and intraabdominal pressure increases
- This increases pressure gradient for venous return and creates a suction effects that moves blood from veins towards the heart
- Increasing rate and depth of breathing increases venous return to the heart
Describe how the skeletal muscle pump works in terms of venous return
Contraction of muscles pushes blood towards the heart as large veins in limbs lie between the skeletal muscles.
Acute CV responses to exercise?
- Sympathetic nerve activity increases
- HR and SV increase. This increases the cardiac output (CO = SV x HR)
- Sympathetic vasomotor nerves reduce flow to kidneys & gut - vasoconstriction
- In skeletal and cardiac muscle, metabolic hyperaemia overcomes vasomotor drive - vasodilatation
- Blood flow to skeletal and cardiac muscles increase in proportion to metabolic activity
- The increases in CO increases systolic BP. The metabolic hyperaemia decreases SVR and decreases DBP (i.e. the pulse pressure increases)
- Post exercise hypotensive response
Chronic response to exercise?
• People who exercise regularly will have reduced blood pressure
Adaptations of coronary blood flow?
- High Capillary Density
- High Basal Blood Flow
- High Oxygen Extraction (~75% compared to 25% whole body average) under resting conditions
Extra O2 in the heart (when required) cannot be supplied by increasing O2 extraction as there is already ____1_______
Extra O2 can only be supplied by increasing ____2_____
1 very high rate of oxygen extraction
2 coronary blood flow
Decreased Po2 causes ______ of the coronary arterioles
vasodilatation
Direct sympathetic stimulation from __1___ results in __2____
Overall there is ___3____ as the increased CO and SV results in metabolic hyperaemia and stimulation of adrenaline release acting on ___4____
1 Alpha receptors stimulated by noradrenaline
2 vasoconstriction
3 vasodilatation
4 beta 2 receptors
Peak left coronary flow occurs during ___1 __so shortening this (e.g. increasing heart rate) ____2____ coronary flow. Even if you don’t have diseased arteries you could still get ischaemia because of fast heart rate.
1 diastole
2 decreases
Most of the coronary blood flow and myocardial perfusion occurs in _______ when the subendocardial vessels from the left coronary artery are not compressed
diastole
The brain is supplied by…
internal carotids and vertebral arteries
___1_____(formed by two vertebral arteries) and _____2___ arteries anastomose to form ___3______
1 basilar
2 carotid
3 The Circle of Willis
Major cerebral arteries will arise from _____1____ meaning cerebral perfusion should be maintained even if _____2___________
1 The circle of Willis
2 one carotid artery gets obstructed
Direct sympathetic stimulation has ___1____ effect in overall cerebral blood flow. Changes __2___ brought around by nerves. It is an intrinsic ability. Participation of the brain in baroreceptor reflexes ___3____
1 little
2 are not
3 negligible
If MABP in brain rises, resistance vessels automatically _______1_______
If MABP falls, resistance vessels automatically _________2________
1 constrict to limit blood flow
2 dilate
Increased Pco2 causes __1___ this is why ____2____ could lead to fainting.
Cerebral vasodilatation
hyperventilation
Increasing ICP (e.g. due to head injury, or brain tumour) decreases____1____ and ____2_____. Also, some conditions which increase ICP can lead to ____3______
1 Cerebral perfusion pressure
2 Cerebral blood flow
3 failure of autoregulation of cerebral blood flow
The blood brain barrier refers to…
The very tight intercellular junctions between cerebral capillaries.
Cerebral capillaries are highly permeable to ____1_____ Glucose crosses the BBB by _______2______ Brain has obligatory requirement for glucose. The BBB is exceptionally impermeable to ____3____ This helps protect brain neurones from ____4_____
1) O2 and CO2
2) Facilitated diffusion using specific carrier molecules
3) hydrophilic substances such as ions, catecholamines, proteins etc
4) fluctuating levels of ions etc in blood.
Hypoxia causes _____1____ of pulmonary arterioles which is the opposite effect of hypoxia on systemic arterioles. This helps _________2_______
1 Vasoconstriction
2 divert blood from poorly ventilated areas of lung
Resting blood flow in skeletal muscles is low because of ________1___________
During exercise, ______2_______ overcomes sympathetic vasoconstrictor activity. Circulating adrenaline causes ___3_____ (B2 adrenergic receptors)
Plus, increased cardiac output during exercise _________4___________
1 sympathetic vasoconstrictor tone
2 local metabolic hyperaemia
3 vasodilation
4 increases skeletal muscle blood flow many folds
Plasma proteins generally ______ cross the capillary wall
cannot
Starling forces favour filtration at __1___ end and reabsorption at __2___ end
1 arteriolar
2 venular
Major forces involved in systemic trans capillary fluid flow?
PC - capillary hydrostatic pressure
pi sign C - capillary osmotic pressure
During a day filtration exceeds reabsorption by 2- 4 litres. Excess fluid is returned to the circulation via _______________
the lymphatics as lymph
Pulmonary capillary hydrostatic pressure is low which means the forces favouring __1___ are much lower allowing the lungs to resist __2___
1 filtration
2 oedema
Oedema causes diffusion distance to ___1_____ which results in ____2_____.
1 increase
2 compromised gas exchange and decreased compliance
4 causes of oedema
Raised capillary pressure
Reduced plasma osmotic pressure
Lymphatic insufficiency
Changes in capillary permeability
Heart failure results in __1___ oedema, lymphatic insufficiency usually causes ___2____ oedema
1 pitting
2 non-pitting (as fluid cannot be pushed into the lymphatics if they are blocked hence there will be no pitting).
If pressure is raised in left atrium this will put a back pressure in the ____1____, raising hydrostatic pressure in the ___1___ so fluid will be pushed into the __2___ causing ___3___.
Right ventricular failure will cause _____4______ as this raises hydrostatic pressure in the ___5_____
1 pulmonary veins 2 lung tissue 3 pulmonary oedema 4 peripheral oedema of the ankles and sacrum 5 systemic capillaries
An alternative way to measure MAP?
DBP +1/3 of the pulse pressure
What is the normal range of MAP?
70-105mmHg
What produces dicrotic notch in atrial pressure curve?
Vibration of valve shutting
What is adenosine?
A potent vasodilator
