Week 11 Flashcards
Cardiovascular and respiratory responses comprise:
Local vasodilation in exercising muscle
-upon which is superimposed
Exercise reflex:
-cortical influences (volition)- central command
Increased respiration which provides increased O2 supply to muscles
Comparison of cardiovascular responses evoked by static and dynamic exercise
Static exercise: higher HR is static, increased ABP greater in static (Increased SP and DP)
In static, increased muscle blood flow during contraction is small, increased blood flow occurs after
Local effects in exercising muscle
Exercise hyperaemia- “local” vasodilation
—K+, Pi, adenosine
—graded with exercise intensity
— tends to decrease TPR
Counteracted by mechanical influences of contraction:
Therefore:
-increase in muscle blood flow is rhythmic in dynamic exercise, tends to decrease TPR
Muscle blood flow may not increase during static exercise- hyperaemia occurs after contraction- TPR tends to increase during static contraction
NB: skeletal muscle pump helps to maintain or increase EDV
-rhythmically in dynamic exercise
-at onset only, in static exercise
Exercise reflex
K+, Pi, adenosine also stimulate metaboreceptors in exercising muscle: and joint receptors stimulated in dynamic exercise
Afferent activity—> CNS
—> subthalamic locomotor region (SLR) “exercise integrating are”
Reflex:
-increased respiration (increase motor activity to diaphragm and intercostal muscles)
-increased HR and contractility (increased sympathetic, decreased parasympathetic) -> increased CO
-increased sympathetic noradrenergic activity:
—GIT, kidney, skin and all skeletal muscle-> vasoconstriction -> TPR
Via connections with:
-central respiratory neurones
-cardiac vagal motor neurones
-RVLM to sympathetic pre-ganglionic neurones
Central command- from cortex- to SLR- reinforces exercise reflex. Responsible for 10% of total changes
Overall exercise
Sympathetic vasoconstriction in exercising muscle is overcome by exercise hyperaemia- functional sympatholysis, complicated by mechanical compression
In dynamic exercise increase in CO is distributed to exercising muscle and away from resting muscle, GIT, Kidney, skin
- on balance TPR changes little. Small increase ABP (increase SP and DP)
In static exercise TPR more likely to increase- large increase ABP (Increase SP and DP)
Baroreceptors reflex buffers rise in ABP but set point is increased
Cerebral circulation- pressure Autoregulation- (myogenic vasoconstriction if ABP increases)
Skin circulation- when body temperature increases. Vasoconstriction in skin is overcome by thermoregulatory reflex. Decrease in sympathetic activity- vasodilation
Matching of increase in O2 consumption, CO2 production and increase in Ve during progressive exercise test- dynamic exercise
Reflex increase in respiration is evoked by metaboreceptors- exactly matches increase in CO2 production
PaO2 and PaCO2 and pH remain constant until anaerobic threshold. Ie no stimulation of chemoreceptors
Lactate — fatigue
H+ stimulates peripheral chemoreceptors
Coronary circulation
NB cardiac work= CO x ABP approx
Exercise increases cardiac work
Requires increases coronary vasodilation
Induced by local accumulation of adenosine
Systolic and diastolic pressure raised
Much greater increase in cardiac work in static exercise therefore greater coronary vasodilation is required
So static exercise more likely to be a problem for patients with coronary artery disease- angina, ST segment changes, ectopic beats, MI
Advise- dynamic exercise
Comparisons
Static exercise- fatigue occurs relatively quickly
-O2 delivery to contracting muscle is limited
-metabolites accumulate in muscle K+, Pi, adenosine and lactic acid
—stimulate metaboreceptors more
—enhances exercise reflex
—produces pain
Cardiovascular risk- increase ABP during contraction
-stroke, aneurysm
-may be decrease ABP after contraction. Postural hypotension
Dynamic exercise can be much more prolonged- fatigue takes longer because muscle receives increased blood flow
Good for cardiovascular health
CVS response to exercise
Acute exercise:
Responses include-
- metabolic dilation of muscle blood vessels (eg K+, H+, adenosine ATP, Pi); B-mediated dilation
-increased cardiac output to muscle ~20% at rest to 86% in maximal exercise ie from 1L/min to 22L/min
-requires complex regulation of heart and blood vessels
Chronic exercise (training):
-evokes adaptive responses- increased ability to meet energy demands
-beneficial effects on CVS
-important for athletes, recreationally active and patients with CVS and R disease
-key to rehabilitation from CVS events
CVS response to exercise training (endurance training- aerobic metabolism)
Performance determined by the maximum rate of O2 transport from lungs to mitochondria
VO2 max, muscle perfusion, diffusion
VO2 max: The rate of maximum O2 uptake from the air and/or the rate of maximum O2 use by the mitochondria
NB: during aerobic exercise ventilation is matched to metabolism
O2 uptake in the lungs and therefore VO2 max dependent on:
Maximum achievable cardiac output (resting CO 5L/min, maximum CO in athlete 25L/min)
Haematocrit; 98.5% of O2 carried by RBCs
Resting VO2= 250ml/min-1 (trained and untrained), VO2 max untrained 3L/min, VO2 max trained 5L/min
VO2 max: stroke volume
Aerobic training:
-muscle cells increase length not width
-eccentric hypertrophy stimulated by growth factors released due to aerobic exercise such as insulin-like GF or IGF. Enlargement in size of chamber without increasing wall thickness
Exercise training increases inotropy: for a given preload can produce greater SV at rest
Laplace’s law= P=2T/r
-the effect of Laplaces law on pressure generation in the hypertrophy of exercise training is offset by the changes in inotropy and preload
VO2max: maximal cardiac output
Resting O2 demand unchanged
Resting CO unchanged
SV increased
HR decreased
Eg CO= 5L/min, SV=120ml therefore HR only needs to be 42bpm
Training increases resting EDV (preload):
-increased chamber size
-increased circulating blood volume
-increased central venous pressure
EDV 170ml and SV 120ml
What causes the bradycardia
Increased tonic vagal activity at SAN;
-slower HR, cells more hyperpolarised, decreasing pacemaker potential
Increased local ACh release: at SAN stimulate muscarinic receptors
Decreased intrinsic pacemaker activity
Changes in autonomic activity result in:
-decreased resting HR
-decreased ABP
Also evidence that there is decreased sympathetic activity but mechanism unknown
Maximum Heart Rate
220-age
Similar in all individuals because much more dependent on age
VO2 max: vascular changes
In the heart:
-increased number of arterioles
-increased coronary artery diameter
-decreased vascular resistance
-increased blood flow
-increase perfusion additional capillaries in cardiac muscle
The increase in myocyte length in eccentric hypertrophy is accompanied by:
-increase in capillary number
-increase in capillary: fibre ratio
-decreased diffusion distance (9um)
Angiogenesis
VO2max: vascular changes in muscle
Maximum muscle blood flow is increased by: arterial expansion, increased capillary number
Conduit artery diameter increases eg. Femoral artery diameter increases by 7 -9% decreases resistance increase flow
R proportional 1/r^4
Capillaries: number and density increase, C:F increases, angiogenesis- induced by VEGF, increased SA and decreased distance for diffusion
Increased muscle mitochondria -below sarcolemma- close to capillaries and minimise diffusion distance
Arterioles: number and density increase, increased sheer stress, arterialisation of caps
Increased sheer stress results in:
-upregulation of eNOS
-up regulation of antioxidant enzymes
-increased bioavailability of vasodilator NO
-increased vascular health
Increased muscle myoglobin- oxygen storing increasing availability
VO2max: haematocrit
Training at sea level does not chronically change Hct
Training at altitude can stimulate erythropoiesis and therefore increase performance back at sea level
-effect on Hct on VO2 max and performance exploited
-use of EPO
-use of blood doping
-difficult to detect- EPO endogenous hormone; range or normal Hcts; Hct also dependent on plasma volume
CVS rehabilitation
Main benefits of exercising come from:
Change in balance of autonomic activity:
-decreased sympathetic and increased parasympathetic
-endothelial dysfunction and altered autonomic activity are features of:
—coronary artery disease
—hypertension
—atherosclerosis
-therefore training should improve this
Enhanced blood vessel dilator function:
-decreased reactive oxygen species, increased vasodilator nitric oxide
-exercise training will also lead to beneficial effects on the heart muscle:
—eccentric hypertrophy
—increased inotropy (particularly important in CHF)
NICE guidelines on exercise 19-65 years
People at high risk of, or with CVD should do the following:
-at least 150min of moderate intensity aerobic activity
-75min of vigorous aerobic activity
-a mix of moderate and vigorous activity
-muscle strengthening activity on 2 or more days/week
CVD patients avoid heavy lifting
Decreased resting blood pressure and heart rate
Long term benefits of exercise
Improve cholesterol
Control body weight and shape
Reduce diabetes risk
Reduce stress
Boost confidence
CVS rehabilitation- other benefits
Better understanding of condition
AIDS recovery
Encourages lifestyle changes
Reduces risk of further problems
During moderate whole body exercise (eg running, swimming, cycling)
Vagal influences on the sinoatrial node are inhibited
What does NOT occur as a result of the metaboreceptor reflex stimulated by K+, Pi and adenosine in skeletal muscle
Vasodilation of skeletal muscle blood vessels in the exercising muscle
Effect of local influences instead of
What occurs as a result of aerobic exercise training used in cardiac rehabilitation
Increased nitric oxide and decreased superoxide production in the endothelium
Chronic heart failure (HF)
Heart failure is the inability of the heart to supply adequate blood flow and therefore oxygen delivery to peripheral tissues and organs (or can do but only with large reflex and adaptive changes)
Over 900000 people in the UK have heart failure
30-40% of patients diagnosed with heart failure die within a year
Symptoms: rapid weight gain, shortness of breath, increased swelling in lower body, trouble sleeping, frequent dry hacking cough, loss of appetite
Adaptive processes: (eg sympathetic stimulation, volume loading and hypertrophy) can help the heart initially but can be deleterious in the long-term
Most common cause of heart failure- development post myocardial infarction (MI)
No blood flow (ischaemia) to a specific area of the myocardium
Tissue becomes:
-hypoxic (low O2)
-hypercapnic (high CO2)
-glycolytic and acidotic (low pH)
-nutrient depleted (no substrate supply so reliant on glycogen and fat store metabolism)
-tissue at risk of necrosis
What is a myocardial infarction and how is it treated acutely
Complete occlusion of blood vessel- ischaemia
During MI elevation of ST segment
Primary balloon angiography can break through the thrombus and balloon inflates opening occlusion
Primary stent placement
Reintroduction of blood flow to region of myocardium
Percutaneous coronary intervention PCI: reduces mortality incidence due to acute MI: fewer people dying from acute MI but more people living with heart failure
Other important causes of heart failure
Pressure overload- hypertension, aortic stenosis
Contractile dysfunction- ischaemic heart disease, congential cardiomyopathies
Heart failure leads to changes in the starling ventricular function curve
For a given EDV stroke volume is much lower than normal healthy heart
But in early stages of heart failure the ejection fraction might be preserved: EF= SV/EDV
Baroreceptors reflex stimulation baroreceptors
ABP= CO xTPR
CO = SV x HR
Carotid sinus baroreceptors in internal carotid artery. Carotid sinus nerves into Glossopharyngeal nerves IX
Aortic arch baroreceptors into vagus nerve X
Baroreceptor reflex stimulation
Decreased ventricular function
Decreased SV and CO
Decrease ABP
Decrease baroreceptor afferent activity to CNS
-decreased vagal activity to SAN, increased symp to SAN, increased symp activity to ventricular muscle
-increased HR and contractility (increased SV)
—increased CO
But increasing workload (metabolic demand) of the heart just to maintain SV and CO at rest promotes pathological hypertrophy and beta blockers
Baroreceptor reflex stimulation adrenal gland
Decreased ABP-> decreased baroreceptor afferent activity to CNS
-increased sympathetic activity to adrenal glands
-releases mainly adrenaline (but also noradrenaline) on cardiac myocytes to increase contractility on SAN cells and increase HR
(Patients with HF have chronically high plasma catecholamines (NA and Adr)
Cardiac effects via B1 receptors supplement those of sympathetic nerves
Again increasing workload (metabolic demand) of the heart just to maintain SV and CO promotes pathological hypertrophy
Consequences of persistent adrenergic stimulation of the heart
Initially: increase in cardiac contractility and stroke volume
Later:
-activation B1 adrenoceptors increase cAMP and PKA which phosphorylates key targets in cardiac myocytes-> L-type calcium channels and phospholamban
-phosphorylation of Ca2+ handling proteins which can lead to dysfunctional Ca2+ homeostasis, contractile dysfunction and arrhythmia
Later: pathological hypertrophy
Later: beta adrenoceptor internalisation (reduced expression in B1 adrenoceptors on cardiomyocytes), loss of adrenergic sensitivity partially explains exercise intolerance. No way of increasing contractility during exercise.
Example arrhythmia mech in HF: delayed afterdepolarisations DADs
When you get persistent sympathetic stimulation, elevation in SR calcium load
An increase in beta-adrenoceptor stimulation increases PKA activity
Elevated phosphorylation of L-type ca2+ channel, RyR2 and PLB overall acts to increase the SR ca2+ load and further raise the probability of spontaneous Ca2+ leak
This elevates risk of DADs band triggered activity
-Ca2+ leaking, removal via NCX evoking positive inward current from 3Na+, small depolarising current
-delayed afterdepolarisation DADs- if gets up to threshold for Na+ channels can trigger action potentials, ectopic AP, own spontaneous activity can spread if in multiple cells in ventricle= ventricular arrhythmia
beta blockers and calcium channel blockers should act to reduce the SR Ca2+ load, reducing the risk of DADs, ectopic activity and arrhythmia
Blood volume loading- Kidney and baroreceptor
Decrease ABP
-decrease in baroreceptor afferent activity to CNS - increase sympathetic activity to kidney
-decrease wall tension in renal afferent arterioles
-decrease Na+ delivery to macula densa
—increases renin release
Converting angiotensinogen to angiotensin I—ACE—> increase angiotensin II
Patients with HF have chronically high plasma angiotensin II
Blood volume loading- kidney and baroreceptor angiotensin II
Increases ATII
-adrenal cortex —> aldosterone secretion
-ADH release posterior pituitary
-increase thirst via hypothalamus
—ADH and aldosterone increase water reabsorption
—thirst increase water intake
—increasing blood volume
Blood volume loading consequences
Increase blood volume -> increase central venous pressure> increase rate of cardiac filling -> increase EDV
Initially the increase in blood volume allows SV to be preserved at rest (along with increased contractility)
Later: persistent volume loading go beyond the plateau of starling curve and SV can no longer be sustained
Oedema in heart failure
If there is mismatch in LV and RV CO due to failing heart then blood can start to accumulate in the systemic or pulmonary vascular system
This can lead to an increase in capillary hydrostatic pressure, elevated capillary filtration leading to oedema- worsened by progressive increases in total blood volume
Review of capillary filtration Starlings hypothesis
Pulmonary circulation normal : net loss of fluid from lung into capillary
Pulmonary circulation in Left HF: elevated capillary hydrostatic pressure greater than opposing force, net force driving fluid out capillaries into interstitium, pulmonary oedema, accumulation of fluid in lungs
Pulmonary oedema
Increased diffusion distance for gas exchange- diffusion impairment
Arterial hypoxia
Shortness of breath- feeling of oxygen starvation (primal emotion)
Peripheral chemoreceptor activation
Hypoxia in the lung itself could lead to hypoxic pulmonary vasoconstriction and pulmonary hypertension
Possibly overcome by giving 100% oxygen
Longer term therapy- loop diuretics, ACE inhibitors and AT1R antagonists
Cardiac hypertrophy
High blood pressure (pressure loading) and/or chronic sympathetic stimulation (increased cardiac work) can lead to pathological cardiac mass enlargement. (Valve disease/regurgitation can also cause HF and hypertrophy)
Reducing afterload with vasodilators, surgical valve replacement and beta blocker therapy (to reduce cardiac work) have the potential to reduce development of hypertrophy in HF
But hypertrophy:
-increases susceptibility to ischaemia
-increases incidence of arrhythmias
-increases incidence of sudden death
