Physiology Flashcards
Where does excitation of the heart originate?
In the pacemaker cells of the sino-atrial node
Where is the sino-atrial node located?
In the upper right atrium close to where the Superior Vena Cava enter the right atrium
What is Sinus Rhythm?
A heart controlled by the sino-atrial node is said to be in sinus-rhythm
What is the pacemaker potential?
The pacemaker potential is the slow depolarisation of membrane potential to a threshold
Cause of pacemaker potential?
1) Decrease in Potassium efflux
2) Na and K influx (Funny current)
3) Ca influx due to T-type channels
All these cause a rise in positive charge in the cell, leading to depolarisation
What causes the rising phase of action potential in pacemaker cells?
Activation of long lasting L-type Ca channels leading to Ca influx
What causes the falling phase of action potential in pacemaker cells?
Inactivation of L-type Ca channels and activation of K channels leading to K efflux
Cell to cell spread of excitation in the atria?
Via gap junctions
Significance of slight delay at the AV node?
The conduction is delayed in the AV node. This allows atrial systole (contraction) to precede ventricular systole
What is phase 0 in cardiac myocytes action potential?
Opening of Na channels leading to a fast influx of Na, rising phase of action potential
What is the plateau phase of action potential?
The membrane potential is maintained near the peak of action potential for few hundred milliseconds in cardiac myocytes
How does Autonomic Nervous System influence the heart rate?
Sympathetic stimulation increases the heart rate
Parasympathetic stimulation decreases heart rate
What division of the ANS dominates the resting heart rate?
The vagal nerve - parasympathetic dominates resting heart rate by exerting a continous vagal tone
What is normal resting heart rate?
Between 60-100 beats per minute
How does Atropine affect the heart rate?
The Vagus nerve (parasympathetic) uses Acetylecholine as a neurotransmitter through Muscarinic M2 receptors to slow the heart rate down. However, Atropine is a competitive inhibitor and blocks this, speeding up heart rate. Used in extreme bradycardia
Effect of Vagal stimulation on heart rate?
Vagal stimulation leads to cell hyperpolarization. It takes longer to reach the threshold as the slope of pacemaker decreases; decreasing action potential frequency. Negative chronotropic effect
Effect of Noradrenaline on pacemaker cells?
Noradrenaline causes the slope of pacemaker potential to increase. Hence, pacemaker cells reach threshold quicker and frequency of action potential increases. Positive chronotropic effect
What is autorythmicity of the heart?
The heart is capable of beating rhythmically in the absence of external stimuli
Events during the cardiac cycle
Passive Filling Atrial Contraction Isovolumetric ventricular Contraction Ventricular Ejection Isovolumetric ventricular Relaxation
What produces the first heart sound (Lub)?
When ventricular pressure exceed aortic pressure, the AV valves shut producing the first heart sound.
What produces the second heart sound (Dub)?
When the ventricular pressure falls below aortic/pulmonary pressure: aortic/pulmonary valves shut. This is S1 and signal starts of Systole
What produces the dicrotic notch in aortic pressure curve ?
The valve vibration produces the dicrotic notch in aortic pressure curve. This is S2 and signals Diastole
Cardiac ausculatations
2nd intercoastal right – Aorta, right – Pulmonary
4th intercoastal space – Tricuspid
5th intercoastal space – Mitral
Use both bell and diaphragm
How does arterial pressure not fall to zero during diastole?
The aorta and arteries are elastic. They stretch when filled with blood and recoil when empty. This keeps the blood flowing forward and hence arterial pressure never falls to zero.
Explain the Jugular Venous Waveforms
JVP is an indirect measure of central venous pressure
a - Atrial contraction
c - Contraction of ventricle while tricuspid valve bulges into the atria
v - Ventricular filling, atrial filling leading to rise in atrial pressure
What provides mechanical adhesion between intercalated discs?
The Desmosomes within the intercalated discs provide mechanical adhesion between adjacent cardiac cells
What are contractile units of muscle?
Myofibrils
What are myofibrils made of?
The myofibrils have alternating segments of thick (Myocyin) and thin (Actin) protein filaments. These are arranged into Sarcomeres.
How is muscle tension produced?
Muscle tension is produced by sliding of actin filaments on myocin filaments. Force generation depends upon ATP-dependent interaction between thick (myosin) and thin (actin) filaments
What proteins block Myosin binding sites?
Tropomyosin and Troponin. Calcium causes a conformational change that switches on cross bridge formation.
ATP is only needed for contraction?
False, ATP is needed for contraction and relaxation
When does Calcium influx occur in ventricular muscles?
Calcium influx occurs during the plateau phase
How is more Calcium released from the Sarcoplasmic Reticulum for contractile machinery?
Extracellular Calcium moves into the cell which induces Calcium release from Sarcoplasmic Reticulum
What causes Calcium to go back into the Sarcoplasmic Reticulum?
When action potential has passed, Ca++ influx ceases, Ca++ re-sequestered in SR by Ca++-ATPase, heart muscle relaxes
Significance of the refractory period?
The long refractory period prevents generation of tetanic contraction
Intrinsic control of stroke volume
Intrinsic control of the stroke volume involves change in diastolic length of myocardial fibres
What determines end diastolic volume?
Venous return to the heart
What determines cardiac preload?
End diastolic volume
What does the Frank Starling Law of the heart state?
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 other benefit does the heart receive from maximising stretch
Stretch also increases the affinity of troponin for Ca++
What is afterload?
Afterload means the resistance into which heart is pumping
What happens if afterload increases?
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
Extrinsic control of the heart?
The extrinsic control of the heart involves nerves and hormones
Effect of sympathetic fibres on stroke volume
Sympathetic fibres use the neurotransmitter Noradrenaline. This increases the force of contraction (positive inotropic effect) by increasing activation of Calcium channels. It also has a positive chronotropic effect - increase heart rate
Effect of parasympathetic nerves on ventricular contraction
Very little innervation of ventricles by vagus nerve, very or no effect on stroke volume. Vagal stimulation has major influence on rate, not force, of contraction
Hormonal control of stroke volume
Adrenaline and noradrenaline released from adrenal medulla have inotropic and chronotropic effect
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
Approx 5 litres per minute (70 ml SVx70 bpm=4900ml)
What is pulse pressure?
Pulse pressure is the difference between systolic and diastolic blood pressures
Pulse pressure is normally between 30 and 50 mmHg
What Korotkoffs sound is blood pressure recorded at?
1st - Systolic peak
5th - Diastole when sound disappears
What drives blood flow around systemic circulation?
A Pressure Gradient between the Aorta (AO)
and the Right Atrium (RA) drives the blood around the systemic circulation
Pressure gradient = Mean Arterial Pressure (MAP) – Central Venous (right atrial) Pressure (CVP)
What is mean arterial blood 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”
MAP = 2*Diastole+Systole / 3 (or)
MAP = DBP + 1/3 Pulse Pressure
Mean arterial pressure formula
Mean Arterial Pressure (MAP) = Cardiac Output (CO) x Systemic Vascular Resistance (SVR)
What is Systemic Vascular Resistance?
Systemic Vascular Resistance (sometimes referred to as “Total Peripheral Resistance”) is the sum of resistance of all vasculature in the systemic circulation
What are the major resistance vessels in the body?
The arterioles
How does sympathetic stimulation of arterioles/veins affect Mean Arterial Blood Pressure?
Sympathetic stimulation of the arterioles causes vasoconstriction leading to an increase in systemic vascular resistance, increases MAP
It also causes vasoconstriction in the veins, causing an increase in stroke volume and cardiac output; increasing MAP
Short term regulation of MAP is by?
Baroreceptor complex which are pressure sensors connecting the carotid baroreceptors (Glossopharyngeal nerve-10th) and aortic baroreceptors (Vagal nerve-9th) to the Medulla
What regulates MAP during postural change?
The Baroreceptors Reflex
Baroreceptors Reflexes in the Prevention of Postural Hypotension
The venous return to the heart decreases - effect of gravity upon standing
mean arterial pressure (MAP) very transiently decreases
This reduces the rate of firing of baroreceptors
The vagal tone to the heart decreases and the sympathetic tone to the heart increases. This increases the heart rate (HR) and stroke volume (SV)
The sympathetic constrictor tone increases. This increases the systemic vascular resistance (SVR) - arterioles are the main site for SVR
The sympathetic constrictor tone to the veins increases the venous return (VR) to the heart and stroke volume
What is postural hypotension?
Results from failure of Baroreceptor responses to gravitational shifts in blood, when moving from horizontal to vertical position
What happens if plasma volume falls?
If plasma volume falls, compensatory mechanisms shifts fluid from the interstitial compartment to the plasma compartment
What contains more fluid, intra or extracellular?
Total body fluid = Intracellular fluid (2/3rd) + Extracellular Fluid (ECF) - normally 1/3rd of the total
What controls extracellular fluid volume?
Water and Sodium excess/deficit
Hormones Which Regulate Extracellular Fluid Volume include
The Renin-Angiotensin- Aldosterone System - RAAS Natriuretic Peptides – NPs Antidiuretic Hormone (Arginine Vasopressin) - ADH
What is the limiting step in the RAAS system?
Renin Secretion from the juxtaglomerular apparatus in the kidney is the Rate Limiting Step for RAAS
What causes release of Renin from the juxtaglomerular apparatus in the kidney?
Renal artery hypotension -caused by systemic hypotension (decrease blood pressure)
Stimulation of renal sympathetic nerves
Decreased [Na+] in renal tubular fluid – sensed by macula densa (specialised cells of kidney tubules)
Which cells monitor tubular fluid Sodium?
Macula densa (specialised cells of kidney tubules)
Which cells release Renin?
The granular cells
What acts as a counter regulatory system for the Renin-Angiotensin-Aldosterone System (RAAS)?
Natriuretic Peptides (NPs)
What causes release of Natriuretic Peptides?
Released in response to cardiac distension or neurohormonal stimuli
Effects of Natriuretic Peptides (NPs)?
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
Two types of Natriuretic Peptides?
These are: Atrial Natriuretic Peptide (ANP) and Brain-type Natriuretic Peptide (BNP)
When is Atrial Natriuretic Peptide released?
ANP is released in response to atrial distension (hypervolemic states). It is a 28 amino acid peptide synthesised and stored by atrial muscle cells (atrial myocytes)
Where is Brain type Natriuretic Peptide synthesized?
Heart ventricules, brain (where it was originally identified) and other organs
What natriuretic peptide can be measured in patients with heart failure?
Serum BNP and the N-terminal piece of pro-BNP (NT-pro-BNP, 76 amino acids) can be measured in patients with suspected heart failure
What are anti-diuretic hormones also known as?
Vasopressin. Peptide hormone derived from a prehormone precursor synthesised by the hypothalamus and stored in the posterior pituitary
Secretion of Antidiuretic Hormones is stimulated by?
Secretion stimulated by (1) reduced extracellular fluid volume or (2) increased extracellular fluid osmolality (main stimulus) or increased plasma osmolality
What does increased plasma osmolality mean?
Too much water in the body. A low level of salt in the blood. This can be caused by some medicines, including diuretics and certain blood pressure medicines.
Effects of Antidiuretic hormone
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
Role of antidiuretic hormone is hypervolaemic shock
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)
The resistance to blood flow is mainly controlled by?
The resistance to blood flow is mainly controlled by vascular smooth muscles through changes in the radius of arterioles
Resistance depends on?
Resistance to blood flow is: directly proportional to blood viscosity and length of blood vessel; and inversely proportional to the radius of blood vessel to the power 4
Extrinsic nerual control of vascular smooth muscles
The vascular smooth muscles are supplied by sympathetic nerve fibers. The neurotransmitter is noradrenaline acting on alpha receptors
What is vasomotor tone?
Vascular smooth muscles are partially constricted at rest. This is called the vasomotor tone
How does adrenaline from adrenal medulla affect vascular smooth muscles?
Adrenaline acting on alpha receptors causes vasoconstriction
Adrenaline acting on beta2 receptors causes vasodilation
alpha receptors are predominant in skin, gut, kidney arterioles
beta2 receptors are predominant in cardiac and skeletal muscle arterioles
What mediates intrinsic control of smooth muscles?
Local metabolic changes within an organ influences the contraction of arteriolar smooth muscles
In addition to metabolites, other local chemicals released within an organ (local humoral agents) influence the contraction of arterial and arteriolar smooth muscles
Temperature -
Cold - causes vasoconstriction
Warmth - causes vasodilatation
What causes vasodilation and metabolic hyperaemia?
Decreased local PO2 Increased local PCO2 Increased local [H+] (decreased pH) Increased extra-cellular [K+] Increased osmolality of ECF Adenosine release (from ATP)
Humoral agents that cause vasodilation
Histamine
Bradykinin
Nitric Oxide (NO) - this is continuously released by endothelial cells of arteries and arterioles
What enzyme is involved in continuous release of Nitric Oxide from vascular endothelium?
Nitric Oxide Synthase (NOS) acts on L-Arginine
Types of Nitric Oxide formation
Flow dependent NO formation-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
Receptor stimulated NO formation - Chemical stimuli can also induce NO formation
Humoral agents that cause vasoconstriction
Serotonin
Thromboxane A2
Leukotrienes
Endothelin - this is a potent vasoconstrictor released from endothelial cells.
What is myogenic response?
Myogenic responserefers to acontractioninitiated by themyocytecell itself instead of an outside occurrence or stimulus such as nerve innervation. Myogenic mechanisms in the kidney are part of the autoregulation mechanism which maintains a constant renal blood flow at varying arterial pressure.
Myogenic response to stretch?
If MAP rises resistance vessels automatically constrict to limit flow
If MAP falls resistance vessels automatically dilate to increase flow
Important in tissues like brain and kidneys
Effect of increasing venomotor tone
Increase venomotor tone increases end diastolic volume, increasing stroke volume and hence mean arterial blood pressure
Increasing vasomotor tone increases systemic vascular resistance and hence mean arterial pressure
What acts as a pump to return venous blood to the heart?
Large veins in limbs lie between skeletal muscles
Contraction of muscles aids venous return
Acute cardiovascular response to exercise
Sympathetic nerve activity increases
HR & 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
What does metabolic hyperaemia induce after exercise?
Overcomes vasomotor drive to cause vasodilation
Decrease systemic vascular resistance and decrease diastolic blood pressure
What is shock?
An abnormality of the circulatory system resulting in inadequate tissue perfusion and oxygenation
Steps causing cascade to cellular failure in shock
Shock - Inadequate tissue perfusion - Inadequate oxygenation - Anaerobic metabolism - Accumulation of waste products - Cellular failure
Difference cardiac output and stroke volume
Cardiac Output (CO) is the volume of blood pumped by each ventricle of the heart per minute Where, Stroke Volume is the volume of blood pumped by each ventricle of the heart per heart beat
What are the axes on the Frank-Starling curve
Y axis - Stroke volume (ml)
X axis - End Diastolic Volume (ml)
What is cardiogenic shock?
Cardiogenic shockis a life-threatening medical condition resulting from an inadequate circulation ofblooddue to primary failure of theventriclesof theheartto function effectively (decreased cardiac contractility)
Causes of different types of shocks
Hypovolaemic shock - Loss of blood volume
Cardiogenic shock - Loss of contractility
Obstructive shock - Increase in intrathoracic pressure
Neurogenic shock - Loss of sympathetic tone
Vasoactive shock - Release of vasoactive mediators
Cause of inadequate tissue perfusion
Decrease cardiac output and decrease blood pressure
Causes of hypervolaemic shock
Haemorrhage, vomiting, diarrhoea, excessive sweating
This causes low blood volume - low cardiac output - low blood pressure
Compensatory mechanisms can maintain blood pressure until?
Compensatory mechanisms can maintain blood pressure until >30% of blood volume is lost
What occurs in haemorrhagic shock
Loss of blood volume, hypotension, tachycardia, decrease in pulse pressure, increase in respiratory rate, low urine output
What causes cool periphery in haemorrhagic shock
Increased Systemic Vascular Resistancevia Baroreceptor Reflex
The cardiovascular centre is where in the brain
Medulla
What stimulation decreases slope of pacemaker cells?
Parasympathetic stimulation decreases slope of pacemaker cells, slows conduction via AV node and slows heart rate
What phase of ventricular action potential causes calcium-induced calcium release?
Calcium influx during the plateau phase of action potential
