Physiology Flashcards
Bundle of pacemaker cells
Sinoatrial Node
Location of Sinoatrial node
Upper right atrium proximal to the entry of Superior Vena Cava
A heart controlled by the SA Node is said to be in…
Sinus Rhythm
Only area of the heart where the impulse can pass from the atria to the ventricle
Atrioventricular Node
What is the function of the AV node
To delay the spread of the impulse between atria and ventricle to allow complete atrial systole
Speed the impulse down the ventricular walls to the apex where the excitation occurs
Bundle of His
Purkinje Fibres
Determines the heart rate
Reciprocal action of the parasympathetic and sympathetic
nervous system.
Parasympathetic nerve that controls the heart rate
X cranial or vagus nerve
What dominates the heart under resting conditions
Vagal tone, at rest parasympathetic impulses dominate
Parasympathetic system innovates in the heart
SA and AV node
Sympathetic system innovates in the heart
SA, AV and Myocardium
On an ECG. P is
Atrial depolarization
On an ECG. QRS is
Ventricular depolarization, atrial repolarization is masked
On an ECG. T is
Ventricular repolarization
On an ECG. P to R is
Largely due to AV node delay
On an ECG. S to T is
Ventricular systole
On an ECG. T to P is
Diastole
What can cause changes to action potentials
Nerves Hormones Cardiac disease pH and electrolyte imbalances Drugs
Resting Potential of Ventricular cells
Around -90mV
Phase 4
Outward flux of K+ is dominant
Background leakage of Na+
Na+/K+ ATPase imports K+ exports Na+ regulates membrane potential
In Phase 4 what ion channels are dominant
Inward Rectifier K+ channels or Iki
What drug inhibits the Na+/K+ ATPase
Digoxin - slightly depolarizes membrane so slows heart rate but increases force of contractiom
Threshold Potential
Around -65mV
Maximum Potential reached during Phase 0
Around +30mV
Phase 0
Rapid opening of voltage gated Na+ channels leads to depolarization
Voltage gated Na+ channels quickly deactivate
In which type of cells is Phase 1 most dominant
Cells with a prominent phase 2 such as Purkinje fibres or epicardial cardia muscle
Type of ion channels open in Phase 1
Transient Outward K+ channels or Ito
Phase 1
Outward K+ flow is dominant repolarization
Rapid opening of Ito channels by voltage gated K+ channels
Na+ Channels closed
Phase 2
Due to balance in conductances inward depolarising Ca2+ and outward repolarizing K+ causes a plateau
What is the importance on Phase 2
Entry of Ca2+ into the cell acts as a trigger releasing intracellular Ca2+ from sarcoplasmic reticulum triggering contraction
Where is Intracellular Ca2+ stored
Sarcoplasmic Reticulum
What type of ion pumps lead to the plateau in Phase 2
Long acting Ca2+ or Ica,L
At what voltage are L-type Ca2+ channels activated
Around -30mV
Phase 2- Which K+ pumps are active in 4 but decreased?
Iki or Inward Rectifier Potassium Channels
Phase 2- Which K+ pumps continue to exert repolarizing effect initially but reduce over time?
Ito or Transient Outward Potassium Channels
Phase 2- Which ion pumps are voltage activated and increase over time?
Voltage activated delayed rectifier potassium channels- Ik
- Iks are slower so open later
- Ikr are initial channels
What is the effect of blocking Ica,l or L-type Ca2+ channels?
Reduce duration of Phase 2 and the force of contraction
What is the effect of blocking Ik or delayed rectifier potassium channels?
Increase duration of phase 2
Phase 3
Outward K+ current exceeds Ca2+ entry so repolarization occurs
Why does hyperpolarization occur in Phase 3
L-type Ca2+ channels have inactivated whilst
,Ikr initially the Iks and then Iki dominates in late phase 3, K+ channels have opened
Difference in atrial Cardiac muscle to ventricle in terms of AP
Phase 2 is much less evident as an additional K+ channel causes final hyperpolarization to occur faster
What additional K+ channel causes hyperpolarization to cur faster in Atrial cells
Ultrarapid delayed rectifier potassium channel or Ikur
Phase 0 AV and SA nodes
Activation of voltage gated L-type Ca2+ but no rapid Na2+ so slower depolarization
What 3 time and voltage dependent conductances occur in Phase 4 in AV and SA nodes
Outward flow of K+ is reduced , IK is reduced so repolarising factor is reduced
Inward ICa,L effect gradually increases driving membrane potential up until reaches threshold- Phase 0
End of phase 3 HCN channels activated Na+ influx into cell during depolarization
What is special about HCN Channels
They are activated by hyperpolarization
What do HCN channels do?
Upon activation they trigger a funny current or If, which conducts Na+ into the cell and increase membrane potential slightly
HCN during sympathetic stimulation
Channels activate more readily as sensitive to cAMP as a result the slope of the pacemaker potential is increased increasing heart rate
HCN during parasympathetic stimulation
Block the HCN channels prohibiting Na+ influx so slope of pacemaker potential is increased reducing heart rate
Selective blocker of HCN
Ivabradine,
Used in angina not first line
Reduces heart rate so reduces O2 consumption as a result less toxic build up of waste products alleviating the symptoms
Sympathetic Neurotransmitter
Noradrenaline and adrenaline
What receptor does the sympathetic system activate
B1 adrenoreceptors in nodal and myocardial cells
Effect of activating sympathetic receptor
Gs coupled protein is activated and the alpha subunit stimulates adenyl cyclase to increase intracellular cons of cAMP
What does adenyl cyclase do
Increases conversion of ATP to cAMP
What does cAMP
Acts as a secondary messenger activating several processes in the cell
Sympathetic effect on heart
Increased If and ICa,L- reduces threshold value and increases slope of pacemaker potential Increases contraction Increases Stroke volume Increases Conduction velocity in AV node Automacity increases Reduces duration of systole Increases rate or reactivation Cardiac hypertrophy over long time
Why under sympathetic influence is the contraction and stroke volume increased?
As increased ICa,L more Ca2+ is taken in during phase 2 as a result increased sensitisation of proteins to Ca2+
Why under sympathetic influence is the period of systole reduced?
More Ca2+ is taken in so reaches threshold for Ca2+ needed to trigger contraction faster
Why under sympathetic influence is the reactivation period faster?
As increased Na+/K+ ATPase so membrane potential is restored faster
Chronotropic effect
Those that change the heart rate
Dromotropic effect
Changes rate of conductance in AV node
Automacity
Tendency for non nodal cell to develop spontaneous activity
Lucitropic
Changes rate of Diastole
Parasympathetic Neurotransmitter
Acetylcholine
Parasympathetic Receptor
M2 muscarinic receptors
Effect of activating Parasympathetic Receptor
Gi coupled protein receptor
Alpha subunit inhibits adenyl cyclase
Beta/Gamma dimer opens specific K+ channels
Causes hyperpolarization
What specific K+ channels are activated by Beta/Gamma subunit
G protein inward rectifiers or GIRKs
Parasympathetic effect
Increases threshold reduced pacemaker potential
Reduced If and ICa,L
Reduced atrial contractility
Decreased AV conduction as hyperpolarized
Why is contractility in parasympathetic innovation only on atria?
As no parasympathetic innovation of ventricles
Negative Effect of parasympathetic innovation
May trigger atrial fibrillation or tachycardia as impulse is unable to pass into ventricle
What channels on the Sarcoplasmic Reticulum are activated by extrinsic Ca2+ entering the cytoplasm?
Ryanodine type 2 channels
How does Ca2+ cause contraction?
Binds to Troponin C and shifts tropomyosin out of actin cleft
Cross bridge forms between actin and myosin resulting in contraction
How is Ca 2+ removed from cytoplasm to allow relaxation
Na+/Ca2+ exchanger removes Ca2+ from cell
Ca2+ ATPase activates which pumps Ca2+ into sarcoplasmic reticulum
How does relaxation of muscles occur?
When sarcoplasm concentration of Ca2+ is reduced enough Ca2+ dissociates from troponin c which breaks the cross bridge between actin and myosin
Is cardiac muscle striated?
Yes as light and dark filaments are lined up
What ensures the cardiac cells are mechanically joined
Desmosomes, ensure that tension created is transmitted
What allows the electrical current to pass between cells?
Gap Junctions
What is the contractile unit of a cardiac myocyte?
Myofibril
What is the thin light filament?
Actin
What is the thick dark filament?
Myosin
What is the functional unit in a myofibril?
Sarcomere
What type of reaction is the contraction of cardiac muscle?
ATP dependent, Ca2+ is also required
Why is the refectory period so long in cardiac muscle?
As the Na+ channels are closed and the K+ channels are open so depolarization is unable to occur
What does the refractory period in cardiac muscle prevent ?
Tetanic Contraction, continuous contraction, allowing diastole to occur.
What is cardiac preload
How much the muscle is stretched
What brings about changes in the stroke volume?
Changes in diastolic length of myocardial fibres
What brings about changes in the diastolic length of fibres?
End diastolic volume
What directly effects the end diastolic volume?
The volume of venous return
Starling law of the heart
The more the ventricle is filled (EDV) the greater the volume of blood ejected during systole
What does stretching cardiac muscle do?
Pushes the contraction cardiac muscle to optimum
Increases troponins affinity for Ca2+
Achieved by increasing venous return
Afterload
Pressure heart pumps into
Effect of increased after load
Ventricle can’t pump out full stroke volume
Increases the EDV
As a result of frank starlings mechanics of the heart, contraction rises to overcome
What can chronic high after load or hypertension lead to?
Hypertrophy of the myocardium
When do heart sounds occur
Upon the closing of the heart valves
What is the mitral valve?
This is the left atrioventricular valve
First Heart Sound
Lub formed when the Atrioventricular and Mitral valves close, S1
Second heart sound
Dub formed when aortic and pulmonary valves close, S2
Five stages of the cardiac cycle
Passive filling Atrial Contraction Isovolumetric ventricular contraction Ventricular Ejection Isovolumetric Ventricular relaxation
Difference in cardiac and smooth muscle
No troponin in smooth muscle, calcium binds to calmodulin instead
Whats does the calmodulin Ca2+ complex do?
It activates myosin light chain kinase which phosphorylates the light myosin chain causing contraction
How does smooth muscle relax
cGMP protein kinase G activates a myosin light chain phosphatase
The MLCP de-phosphorylates the myosin light chain causing relaxation
What is the target of most drugs
cGMP is pharmacologically synthesised
What to endothelial cells react to?
Histamine, Bradykinin, ADP, 5-HT
What does the activation of receptors by vasodilation substances trigger
Influx of Ca2+ init the cell, calmodulin complexes form which activates eNOS enzymes.
What do activated eNOs enzymes do
Synthesise NO from L-arginine
Action of NO
Diffuses directly into the smooth muscle cell where it activates guanylate cyclase
Guanylate cyclase
Converts GTP into cGMP- required for smooth muscle relaxation
Protein Kinase for contraction
Protein Kinase A
Protein Kinase for relaxation
Protein Kinase G
Protein Kinase G
Increase Ca2+ ATPase and new Ca2 + membrane ATPase increasing removal of Ca2+ from cytoplasm
K+ channels open hyperpolarising cell membrane
Where is the main site of systemic vascular resistance?
Arterioles
What is resistance related to
Directly proportional to viscosity and length of blood vessel
Indirectly proportional to radius of blood vessel to the power of 4
Is there parasympathetic innervation to vascular smooth muscle?
Very little only penis and clitoris have significant
What does increasing the sympathetic discharge do?
increases vasomotor tone increasing constriction
Adrenalines affect of Alpha receptors
Found on kidney gut skin etc causes vasoconstriction
Adrenalines affect on B2 receptors
In cardiac skeletal muscle etc causes vasodilation
What other hormones cause Vasoconstriction?
Angiotensin II and antidiuretic hormone- intermediate control
Intrinsic control
Matching blood flow to metabolic demands, overrides extrinsic nerves and hormones
What kind of output is the sympathetic nerves
Thoracolumbar
Where do sympathetic nerves synapse?
At ganglion outside the spinal column but not on the organs
What are the post synaptic nerves that innervate the heart called and to which vertebrae do they correspond to?
Cardiopulmonary Splachnic nerves T1 to T5 and lower cervical
What is the cardio plexus
Located posterior to aorta on superior heart border, where the sympathetic fibres mingle with parasympathetic and visceral afferent nerves
What is sympathetic ganglion neurotransmitter?
Acetylcholine
What is the sympathetic neurotransmitter to the organ?
Noradrenaline
What is the parasympathetic neurotransmitter for both the ganglion and the organ?
Acetylcholine
What is the difference between post synaptic nerves in the sympathetic and parasympathetic system?
The parasympathetic nerves are much shorter as the ganglion is located on the surface of the organ itself
Viscerent afferent reflex
Baroreceptros relayed via Vagus nerve
Viscerent Afferent Pain
Relayed by sypathetic system
What percentage of O2 does the coronary circulation absorb under resting conditions?
75%
Intrinsic control of coronary circulation
Decreased pO2 causes vasodilation, metabolic hyperaemia matches flow to demand
Adenosine a by-product of ATP breakdown is a vasodilator
Extrinsic control- functional sympatholysis
Despite sympathetic innervation upon sympathetic vasomotor increase, arterioles dilate due to intrinsic override
What is the effect of increasing the heart rate on coronary blood flow?
As the coronary arteries fill on diastole if you shorten diastole blood flow decreases
Function of the circle of willis
Means if one of the larger arteries are blocked due to anastomoses brain will still be supplied with oxygenated blood- if a branch of it is blocked small area it supplies is deprived
What vessels supply the brain?
Right and left internal carotid arteries
Vertebral arteries form the basilar artery
How long can grey matter survive without O2 before damage
3 minutes
What are the two types of stroke?
Haemorrhage- vessel burst and bleeds into the brain
Emboli- Vessel is blocked off
Within what range is the coronary BP autoregulated?
60-100mmHg MAP
Does sympathetic stimulation or baroreceptor reflex have any effect on the coronary BP
Very little sympathetic and no baroreceptor
MABP rise in coronary causes?
Vasoconstriction to limit blood flow
MABP falls in coronary causes?
Vasodilation to increase blood flow
Affect of a MABP of less than 50mmHg?
Confusion fainting brain damage
What does a decrease in pCO2 trigger?
Vasoconstriction, hence hyperventilation causes you to faint
What other way is the blood flow affected in the brain?
For unknown reasons active areas of the brain have increased blood flow
How do you work out the cerebral perfusion pressure CPP?
CPP=MAP- ICP
ICP is inter cranial pressure usually 8-13mmHg
What can cause an increased ICP and in turn reduce perfusion to the brain?
Head trauma bleeding brain swelling etc
Brain tumour
What is the blood brain barrier?
Formed by the cappiliaries in the brain that have very tight intercellular junctions
What is the Blood brain barrier permeable to?
CO2 O2, Glucose is transported across by facilitated diffusion
What is the blood brain barrier impermeable to?
H+ ions catelchoamines proteins, this protects brain from the effect of fluctuating levels in the blood
What is the pulmonary pressure?
10% of systemic pressure
What is the reason for allow pulmonary pressure?
So the absorptive forces exceed filtration to prevent build up of oedema
