B2 Physiology of Cardiac Muscle Flashcards
What are the functional parts of the cardiac muscle?
Myocyte
Sarcomere
Actin & Myosin
Troponin & Tropomyosin
What is a myocyte?
Bundles of spirally arranged myofibrils
How many myosin molecules are in a myofilament?
300
What are myocytes made from?
Myofilaments
What is a sarcomere?
Basic individual contractile unit
The distance between two Z lines on a myofibril?
What are myofilaments made from?
Myofibrils
How do sarcomeres relate to muscle contraction?
Shortening of lots of sarcomeres - muscle contraction
What is actin?
Thin filament contributing to structure of sarcomere
What is myosin?
Thick filament contributing to structure of sarcomere; has two heads
What does myosin contain that is necessary for muscle contraction?
ATPase
What is regulatory protein complex?
Thin filaments which are made up of actin and a chain of globular protein.
What are the three types of troponin?
T
C
I
What is the role of Troponin T?
Tropomyosin attachment
What is the role of Troponin C?
Ca2+ binding (when it’s released from sarcoplasmic reticulum)
What is the role of Troponin I?
Inhibits actin and myosin binding (Until troponin C has bound Ca2+)
When are troponin and tropomyosin present in the blood?
After myocyte damage (e.g. heart attack)
What is the first step of excitation - contraction coupling (ECC)?
Receptors activated at neuromuscular synapse
What happens after receptor activation in the ECC process?
Release of Ca2+ from sarcoplasmic reticulum
What happens after Ca2+ is released from the sarcoplasmic reticulum?
Troponin- I is released from the troponin molecule
What happens to the actin to allow cross linking of actin and myosin?
Myosin binding sites are exposed
What happens after cross linking of the two filaments?
ATP attaches to the myosin head
What effect does the ATP attachment have on the filaments?
Cross bridges detach
What does the term ‘power stroke’ mean?
Myosin filaments rotate towards the centre of the sarcomere
What happens after the cross bridges detach?
Myosin hydrolyses the ATP
What does the myosin head do with the energy from hydrolysed ATP?
Reorientates itself
How does contraction occur on the level of the sarcomere?
The myosin stays in the same place but binds to different segments of actin, resulting in actin sliding towards the M line
What is the M line?
The vertical mid line of the sarcomere
What type of nerve terminal is involved in cardiac muscle contraction?
Sympathetic
Where are the nerve terminals in cardiac muscle contraction?
SA and AV nodes
What is released at the sympathetic nerve terminals?
Noradrenaline
What does noradrenaline bind to on the post-synaptic membrane?
B1 receptors
What is the result of noradrenaline binding to B1 receptors in the process of cardiac muscle contraction?
G protein gets activated
What is the role of G protein in cardiac muscle contraction?
It converts ATP to cAMP
What is the role of cAMP in cardiac muscle contraction?
It activates B-adrenoreceptor kinase
What is B-adrenoreceptor kinase?
A protein kinase
What is the role of B- adrenoreceptor kinase in cardiac muscle contraction?
Ca2+ in the sarcolemma gets phosphorylated
What effect does Ca2+ phosphorylation have on cardiac muscle contraction
Increased Ca2+ means increased speed and force of contraction
What is transmembrane potential?
The voltage difference across a cell membrane
What causes transmembrane potential?
The accumulation of negative ions within the cell
How is a transmembrane potential set up?
Stimulation of the cell
What does a transmembrane potential result in?
Ion transfer across the membrane
Voltage change
How is an action potential triggered in heart muscle?
Cell to cell depolarisation in cardiac myocytes
Spontaneous in cardiac pacemaker cells
What is the difference between action potentials triggered betwene cardiac myocytes and in pacemaker cells
In myocytes there is a fast response
In cardiac pacemaker cells there is a slow response
Why are action potentials prolonged in cardiac muscle?
To allow for complete atrial systole before ventricular systole starts.
What happens during repolarisation?
K, Na and Ca returns the cell membrane to resting potential
Myocyte in refractory period- will not respond to a further stimulus.
What are the cardiac pathways through the heart?
SAN -> AVN -> Bundle of His -> Bundle branches -> Purkinje Fibres
How long does the cardiac cycle usually last (how long is a single heart beat)
0.8s
What is the average person’s heart rate?
72 beats/min
What are the two basic components of the cardiac cycle?
Systole and diastole
How do you calculate heart rate?
time divided by speed
How is the direction of blood flow controlled?
Valves
How many phases are in the cardiac cycle?
5
What is the first phase of the cardiac cycle?
Atrial systole
What does the P wave represent on the ECG?
Atrial systole
How much more blood the ventricles from atrial systole?
30%
Which valves are open during atrial systole?
Mitral and tricuspid
What is the benefit of atrial systole over passive filling of the ventricles?
More blood enters the ventricles
Ventricles are stretched improving the strength of contraction
What is Starling’s law?
The ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return.
What is the second phase of the cardiac cycle?
Isometric ventricular contraction
What happens to the ventricles in the second phase of the cardiac cycle?
The ventricles change in shape but not volume and the valves are still closed.
Atrial diastole
Where is phase 2 of the cardiac cycle on the ECG?
The peak of the QRS complex
What causes the first heart sound (S1/’Lub’)
The Mitral and Tricuspid valves closing
What causes the C wave?
Blood bulging back into the atria and against the valves causing a small pressure increase.
What is the third phase of the cardiac cycle?
Ejection phase
What happens during the ejection phase of the cardiac cycle?
50%-70% of the ventricular contents is ejected until the pulmonary/aortic valves close
What part of the ECG represents the ejection phase?
ST segment
When do the aortic and pulmonary valves close?
When the aortic/ pulmonary trunk pressure is higher than the ventricles
What causes the second heart sound (S2/’Dub’)?
The Aortic and Pulmonary valves closing
What is the fourth phase of the cardiac cycle?
Isometric ventricular relaxation
What happens during isometric ventricular relaxation?
Cardiac myocytes repolarise All valves closed Both chambers are in diastole Ventricuar pressure falls Atria fill from veins so the atrial pressure starts to rise
What part of the ECG represents isometric ventricular relaxation?
T wave
What is the fifth phase of the cardiac cycle?
Slow filling
What happens during slow filling?
Mitral/ Tricuspid open
Blood from veins filling atria
Pressure in atria eventually rises to above ventricular pressure
What part of the atrial trace represents slow filling?
V wave
How much of the venous blood actually enters the ventricles?
70%
What factors influence cardiac output?
Stroke volume
Heart rate
What is the another name for Starling’s law
Frank-Starling Effect
Why does a higher diastolic volume mean higher contractility mean a higher stroke volume?
Increasing fibre length results in increased velocity of contraction
Increasing diastolic volume increases the length of the cardiac muscle fibres in the ventricles
What does the P-R interval show?
The period of time from onset of P wave to start of QRS complex (normally 0.12-0.2s)
What does the Q wave represent?
Excitation of intraventricular septum
What does the R wave represent?
Excitation of apex and free walls
What does the S wave represent?
Excitation of regions near the base of the heart
How long does the QRS complex last?
0.06-0.1s
What kind of shape does a normal T wave have?
Assymetrical
True or false? The T wave may be followed by a small U wave repolarisation of papillary muscle
True
What does the ST segment show?
The period between the end o ventricular depolarisation and the beginning of ventricular repolarisation
What does the QT interval show?
Total time taken for depolarisation and repolarisation of the ventricles
Why is it that the after a myocardial infarction, the ST segment can appear raised or lowered?
Baseline changes
How long is the QT interval on average?
0.35-0.45s
True or false? QT interval varies with heart rate?
True
What is sinus rhythm?
Heart rhythm is determined by the SA node
What cells are responsible for generating the spontaneously unstable membrane potential?
Pacemaker cells
What is the normal sinus rate range?
60-100 beats/min
What is bradycardia?
Slow heart beat (
What is tachycardia?
Fast heart beat (>100 beats/min)
What is the commonest form of arrhythmia?
Atrial Fibrillation
What increases the prevalence of atrial fibrillation?
Age
How is atrial fibrillation caused?
Multiple re-entrant circuits sweeping around atrial myocardium which may hit the SA node causing irregular ventricular contraction
How would atrial fibrillation present on an ECG?
P-Waves absent
Wavy irregular baseline of fibrillation waves - 300-600 beats/min
What is inotropy?
Force of contraction
What is chronotropy?
Timing of impulse firing/ heart rate
What is the effect of digoxin on the heart?
Cardiac glycoside
Increases force of contraction
Decreases conduction in AV node
What is the effect of adrenaline on the heart?
Increases heart rate, inotropy and automaticity
Between digoxin and adrenaline, which drug doesn’t have an effect on automaticity?
Digoxin
What are adrenaline’s pharmalogical mechanisms of action?
Acts on B1-adrenoreceptors via cAMP on SAN, atrial muscle, AVN and ventricular muscle
What types of cells does the cardiac muscle have?
Myocardial cells
Conduction cells
What are myocardial cells?
Cells responsible for generating pumping pressure to pump blood around body; cells- connected
What are conduction cells?
Cells responsible for rapidly spreading electrical signals to myocardial cells
How are myocardial cells connected?
Via intercalated discs with gap junctions.
Why do conduction cells spread electrical signals to myocardial cells?
To coordinate pumping.
Give an example of conduction pathway cells?
Bundle of His
Purkinje fibres
What are the three layers in the walls of blood vessels known as?
Tunics
What is the innermost layer of a blood vessel, histologically?
Tunica Interna (Intima)
What is the middle layer of a blood vessel, histologically?
Tunica Media
What are the properties of the tunica interna/intima?
Continuous with endocardial lining of heart
Smooth surface so blood flows through smoothly
Simple squamous epithelium
What are the qualities of the simple squamous epithelium in the tunica interna?
Short diffusion path
Site where chemical signals are sent/received
Site for synthesis of various agents
What are the qualities of the basement membrane in the tunica interna?
Provides physical support base for epithelial layer.
Framework of collagen fibres
Anchors epithelium to underlying connective tissue
Regulates molecular movement
What are the qualities of the internal elastic lamina in the tunica interna?
Thin sheet of elastic fibres
Variable number of window-like openings (facilitate diffusion from tunica interna to tunica media)
What allows for the diffusion of materials from the tunica interna to the tunica media?
Window like openings in internal elastic lamina of tunica interna
What is the tunica media?
Muscular and connective tissue layer
What layer varies the most among different vessel types?
Tunica media
What is the primary role of muscle cells?
To regulate the diameter of the lumen
What does the tunica media mainly consist of?
Smooth muscle cells
Elastic fibres
When does vasoconstriction occur?
Sympathetic stimulation
Vascular spasm to limit blood loss after damage
What separates the tunica media from the tunica externa?
External elastic lamina
Between the tunica media and the tunica externa, which layer does the external elastic lamina belong to?
Tunica media
What is another name for the tunica externa?
Tunica Adventitia
What is the tunica externa?
Outer covering of blood vessel
What is the tunica externa made from?
Elastic and collagen fibres
What type of nerve does the tunica externa contain?
Autonomic
What is the term used to describe tiny blood vessels that supply the tissues of the vessel walls?
Vasa vasorum
What does vasa vasorum mean?
Vessels to the vessels
Where can you see vasa vasorum?
The aorta
What are the roles of the vasa vasorum
Supplying vessel wall with nerves and self-vessels
Helps anchor vessels to surrounding tissues
What are the roles of the aorta/large arteries?
Contain blood at high pressure
Distributing blood to smaller vessels
What are larger arteries known as?
Elastic arteries
Why are vasa vasorum frequent on larger arteries
Poor oxygen diffusion across thicker surfaces (i.e. larger arteries)
What are smaller arteries known as?
Muscular arteries
What is the role of smaller arteries/ arterioles?
Site of flow control since there is a significant pressure drop across arterioles
Why are larger arteries more elastic?
They have a greater proportion of tunica media which contains the elastic fibres
What are the vessels with the smallest diameter called?
Capillaries
What are the qualities of capillaries?
Diameter comparable with blood cells Extensive network Total cross sectional area large Thin walled Tunica media almost absent Occasional pericytes
What are the three types of capillary?
Continuous
Fenestrated
Discontinuous
What is the most common type of capillary?
Continuous
What are fenestrated capillaries?
Capillaries found in tissues with high exchange function - endothelium appears to have pores for exchange- these are known as fenestrations
What is the structure of fenestrated capillaries?
Regular, contain diaphragm material
What organs would have a high exchange function?
Small Intestine
Kidney
Endocrine Glands
Where are discontinuous tissues found?
In tissues where there is cell as well as molecule exchange.
What organs would have cell as well as molecule exchange?
Liver
Spleen
What are the qualities of discontinuous capillaries?
Gaps between endothelial cells
Irregular fenestrations
Large sub-endothelial space
Sub-endothelial space occupied by specialised cells
What is the primary purpose of venules and veins?
To be a low pressure collecting system
What are the structures of venules and veins?
No internal elastic lamina underlying endothelium
Relatively thin tunica media for lumen size
True or false? Venules and veins have the abilility to change their capacity
True - some capacity
How do the venules and veins move blood back to the heart?
Valves and ‘muscle pump’.
What is the cardiac muscle made of?
Cardiac myocytes
What junctions are between intercalated disks?
Gap
Adherens
How are signals transmitted between intercalated disks?
Electro-chemical coupling
Mechanical link
How is it that the heart can function aerobically?
Metabolic substrates
What does blood pressure depend on?
Cardiac output and peripheral resistance
What factors affect peripheral resistance?
Blood viscosity
Dimensions of vessel
Blood volume
What are the properties of lymphatic vessels?
Lined by endothelium Extremely low pressure Thin walled (Normally endothelium only) Valves Non-continuous circulation
Why is lymphatic circulation non-continuous?
It drains fluid from tissues and ultimately drains it into the venous system, it’s doesn’t find its way back to tissues
What does lymph filter through?
Lymph nodes
What is the structure of smooth muscle?
Individual long thin cells (spindle shaped)
Actin-myosin contractile system not in sarcomeres
Central oval shaped nuclei
In comparison to striated muscle, does smooth muscle have more or less contractility?
More
What is the speed of smooth muscle contraction in comparison to striated?
It is slower
How is smooth muscle able to maintain tension?
Low ATP consumption
Where is smooth muscle typically found?
Walls of vessels and tissues
Is smooth muscle somatic or autonomic in terms of nerve control?
Autonomic
What kind of pressure do individual tissues generally start off with?
High
Why do different tissues have different pressures?
They can choose what blood pressure they want
Other than heart rate and peripheral resistance, what else determined cardiac output?
Tissue demand
How is tissue flow locally determined?
Tissue demand; acts by changing resistance
What formula is used to calculate blood flow?
Change in pressure gradient / Resistance
What is the average cardiac output in humans?
5L/min
What happens to cardiac output if there is an increase in venous return?
Cardiac output increases
True or false? Blood pressure and cardiac output are independent of each other
True
How can you relate blood flow to the radius of the vessel?
Flow is proportional to the 4th power of the radius of the vessel.
How is blood flow mechanically controlled?
Muscle sphincters in pre-capillary arterioles constrict/open the vessels (changing vessel radius)
Is flow within a vessel linear?
No
What is the effect of pressure on vessels?
Pressure distends vessels decreasing peripheral resistance
What is the effect of blood pressure on blood flow?
Blood pressure increases blood flow
What is peripheral resistance?
The friction-like force decreasing blood flow along a vessel
How is peripheral resistance/flow measured
Pressure drop/ flow
How is blood flow increased during exercise?
Increase in blood pressure from profound decrease in resistance
Can an increase in blood pressure result from a decrease in peripheral resistance?
Yes. If there is an increase in venous return from the reduced peripheral resistance it can increase cardiac output and therefore blood pressure
What happens chemically during exercise?
Metabolic waste products cause local vasodilation
Hypoxia
Increased CO2
Sheer stress (NO)
How is blood pressure neurologically controlled?
ANS-Keeps systemic BP high
Sympathetic control
What are the centres in the brain responsible for controlling BP?
Vasomotor centre in medulla
Vasoconstrictor
Vasodilator
Cardioinhibtory
How do sympathetic nervous fibres work to control blood pressure?
Release noradrenaline (NA) NA binds to a-receptors -> Vasoconstriction-> Increased peripheral resistance = Increased BP
How do sympathetic fibres (SNS) affect heart rate?
Increasing heart rate
Inotropic
Lusitropic
What does continuous constriction mean?
At rest there is underlying SNS though it can be turned off with anaesthesia
Where are arterial baroreceptors located?
Aortic arch
Carotid sinuses
Baroreflexes
How are carotid sinus baroreceptors stimulated?
Stretch - Signals transmitted to brain stem via afferent limbs of cranial nerve
Very sensitive
How do baroreflexes work to control blood pressure?
Cause increased/decreased sympathetic outflow -> constriction/ relaxation of pre-capillary sphincters
What happens to our blood flow when we stand up?
Fall in blood pressure
Vasoconstriction by SNS
Arteries increase in BP
Veins increase in venous return
Where can other arterial baroreceptors be found?
Low pressure receptors
Atrial stretch
Chemoreceptors
CNS Ischemia
Where would low pressure receptors be found?
In lower pressure part of circulation
What do atrial stretch receptors do?
Cause renal arteriolar dilation
Cause a decrease in ADH
How do chemoreceptors detect a decrease in blood pressure?
A decrease in PaO2
What is pressure diuresis?
Increased BP causes increased blood flow to kidneys -> increased urination and decreased BP
What happens to blood pressure when there is an increased salt and water uptake?
BP increases
How does kidney disease relate to BP?
A higher BP is required to remove the same amount of salt and water
What does RAAS stand for?
Renin Angiotensin Aldosterone System
What do the kidneys rely on to function that the heart produces?
High blood pressure
What happens in the kidneys if blood pressure decreases?
The juxtaglomerular apparatus releases renin
Is the RAAS system long term or short term? Why?
Long-term
Use of hormones
What does renin do after being released?
Converts angiotensinogen to angiotensin I (both are inactive)
What happens to angiotensin I after being produced?
It is converted to the active form - angiotensin II by ACE
What are the roles of angiotensin II?
Causes vasoconstriction, vascular hypertrophy and release of aldosterone
What receptors does angiotensin act on?
AT1 and AT2
What is the role of aldosterone?
Induces salt and water retention
How does increasing salt and water retention increase blood pressure?
Salt itself draws water towards it via osmosis.
Increasing water retention increased blood volume and therefore blood pressure.
Are there any other hormonal mechanisms for blood pressure control?
Natriuretic peptides
Arginine vasopressin
How do Natriuretic peptides control blood pressure?
Decrease in BP
They respond to stretch
Salt loss
Vasodilation
How does arginine vasopressin (ADH) control blood pressure?
Increase in BP
Vasoconstriction
Water retention
What do ACE inhibitor drugs usually end in?
-pril
What do angiotensin recepto blockers (ARBs) usually end in?
-sartan
What do antimineralcorticoids do?
Diuretic- Interfere with aldosterone by stopping it from retaining Na+ and water -> causes urination
What do alpha blockers generally do?
Block alpha receptors so noradrenaline can’t bind
Decrease peripheral resistance and BP
Decrease heart rate
What do beta blockers generally do?
Bind to beta receptors so adrenaline and noradrenaline from SNS can’t
What do calcium antagonists do?
Inhibit Ca2+ from entering smooth muscle cells.
This results in vasodilation because the smooth muscles in sphincters don’t contract.
What do calcium antagonist drugs usually end in?
-ipine
