Week 8 Flashcards
Vasoconstriction and vasodilation of arterioles alter resistance to flow
Vasodilation- increases flow
Normal tone-all arterioles slightly constricted at rest
Vasoconstriction- decreases flow
Controlled by:
-endothelial factors
-local mechanisms
-central neural mechanisms
-hormonal mechanisms
Constriction of arterioles
Constriction of arterioles to one organ decreases flow to that organ. Eg skin in cold conditions
Constriction of arterioles to multiple organs can increase TPR and therefore increase ABP
Useful for maintaining ABP during standing or haemorrhage
Endothelial control
Dilation:
-NO synthesised continuously by nitric oxide synthase converting L arginine. Leads to fall in Ca2+ levels in SMC causing vasodilation, helps to increase coronary blood flow in exercise when cardiac activity and metabolism are increased
-prostaglandins PGE, PGI2, EDHF(endothelium derived Hyperpolarisation factor)
-lots of triggers: circulating hormones, paracrine hormones, shear stress due to increased blood flow and local hypoxia
-in coronary artery disease NO synthesis reduced, this limits increases in coronary flow in exercise and limits cardiovascular ability
Constriction:
-endothelins: Ang-II, trauma, acts via intracellular calcium release, increases levels leads to contraction. Some forms hypertension can be treated with endothelin blockers
-thromboxane
-PGF
Local factors metabolic mechanisms
Adenosine, K+, CO2, H+- vasodilator
Lactate
Vasodilation, increased blood flow
Resistance vessels close by are very sensitive to these byproducts and vasodilation of arterioles occur locally in tissue. Increase oxygen and nutrient supply to tissue either by action on vascular smooth muscle or endothelium
Active or functional hyperaemia
An increase in flow due to an increase in the metabolic activity
Proportional to need
Reactive hyperaemia
Transient increase in flow seen after period of no flow usually due to arterial occlusion
Eg seen in muscles after isotonic contraction such as weightlifting. Thought to be due to build up of metabolites during occlusion which are then washed out in hyperaemia causing vasodilation
Central neural mechanisms
Most vascular smooth muscle has tonic vasomotor tone due to ongoing sympathetic nerve activity SNA
- decreased SNA= vasodilation
-normal tone (some degree of vasoconstriction)
-increased SNA= vasoconstriction
All vessels including skeletal muscle a1 adrenoceptors
Skeletal muscle also has B2 adrenoceptors
when NA released from increased SNA binds to a1 causing vasoconstriction but binds weakly to B2 receptor
In response to increased sympathetic nerve activity the a1 receptor effect predominates in skeletal muscle
Little or no parasympathetic innervation (only in exocrine glands of head and genitalia)
Hormonal mechanisms adrenaline
What if plasma adrenaline increases
The presence of a and B receptors on arterioles indicates that circulating adrenaline will also be capable of changing radius of arterioles
Although primary effect of circulating adrenaline is increasing HR and contractility it tends to cause vasodilation as it has a high affinity for B2 receptors
However as plasma adrenaline increases the dominant receptor response changes to a receptor causing vasoconstriction
In response to circulating adrenaline the B2 receptor effect predominates in skeletal muscle (fight or flight)
Hormonal mechanisms
ADH (vasopressin)— vasoconstriction V1 receptor
Angiotensin II— AT1 receptor causing vasoconstriction
Local factors
Myogenic mechanisms: reflex vasoconstriction in response to increase intravascular pressure, when lumen suddenly expands smooth muscle responds by contracting to restore original diameter
Autoregulation: metabolic and myogenic. Resistance vessels dilate at low pressure to maintain optimal flow and constrict at high pressure.
- cerebral vessels autoregulate between ~60-150mmHg
- kidney vessels autoregulate between ~80-200mmHg
A-vO2 difference
Depends on oxygen demand in tissue
Large a-vO2 difference (eg in heart) high oxygen consumption
Smaller a-vO2 difference (eg kidney and skin) consume less oxygen
Vascular anatomy
Left coronary and right coronary artery
Lines epicardial surface
Acts as distribution vessels, branches into myocardium acts as resistance vessels
Ventricles have higher supply than atria, LV higher blood supply
Coronary arteries derived from aorta just distal to aortic valve
Coronary veins adjacent to arteries, venous drainage into coronary sinus which empties into right atrium
Some drained via thesbian veins, small drop in O2 content in systemic blood
Coronary arteries
Supplies the myocardium and must maintain continues flow for normal function (low capacity for anaerobic metabolism)
Receives ~5% CO at rest
Extracts almost maximum amount of O2 possible at rest
Very large a-Vo2 difference even at rest high oxygen consumption
In coronary circulation the regulation of flow is responsible for matching oxygen supply to metabolic demand
Any increased demand for O2 must be met by large flow increases
Large endothelial surface area for exchange, reduces diffusion distance will facilitate oxygen delivery to tissues. 1 capillary per myocyte
Cardiac tissue myoglobin
Has 3.4g/l myoglobin
Can only bind 1 molecule oxygen much higher affinity than Hb
In capillaries coronary circulation Hb can handover oxygen to myoglobin inside cardiac muscle cells
This myoglobin transfers oxygen to next myoglobin molecule and so on, speeds up diffusion oxygen through muscle cell to mitochondria
Control of coronary flow
Coronary arteries exhibit myogenic auto regulation in pressure range 50-150 mmHg
Any change in pressure met with change in resistance to maintain flow
Coronary flow reserve- difference between resting level of flow and maximum flow that could be obtained by dilating vessels, used as an indicator of the ability of flow to increase when heart is stressed, reduced in some cardiac conditions
Allows blood flow to increase 5 times above resting auto regulatory level when CO increased
Some sympathetic control but overridden by local control
Metabolic/functional hyperaemia dominant form of regulation
An increase in metabolic activity fall in coronary blood flow or fall in myocardial PO2 release adenosine (breakdown product of ATP)
Adenosine is a vasodilator acts by reducing intracellular Ca2+ in vascular smooth muscle cells
Prostaglandins
Low O2, high CO2
NO
K+ (extracellular K+ levels also rise when cardiac work increases may contribute to initial increase in coronary perfusion but is unlikely to mediate sustained rises in coronary flow)
Vasodilation increases blood flow
Flow interruption
Oxygen deficit myocardial hypoxia
Stenosis of left coronary artery- commonly occurs in large epicardial arteries, needs to exceed 60-70% reduction in diameter to have significant effect on flow
Coronary artery disease: such as atherosclerosis, also causes endothelial damage and dysfunction, prostacyclin, falls in NO
Cardiac tissue hypoxia—> angina—> stable angina (fixed stenosis, demand ischaemia, not normally life threatening). Unstable angina—> (thrombus) indicates danger of vessels becoming completely occluded, supply ischaemia. Interventions; balloon angioplasty, stent, coronary bypass graft surgery
Left coronary flow
Most blood flows to the left myocardium during diastole (85%)
Aortic pressure (Pin) during diastole determines flow
Max during early diastole
At high HR diastole is shortened and reduces time for perfusion
Coronary perfusion pressure: aortic diastolic pressure- LVEDP
Extravascular compression in left ventricular wall
Contracting myocytes collapse vessels
Arterial blood is forced back towards aorta
Reversal of blood flow through vessels supplying the left ventricular wall during systole (extra vascular compression)
Must maintain totally secure O2 supply to brain tissue
Grey matter (receives 100ml/min/100g VO2 at rest~7ml O2/min/100g)- high oxidative metabolism, very sensitive to hypoxia
Low oxygen leads to: loss of consciousness>4 min leads to neuronal damage
Local flow alters according to activity (metabolic/functional hyperaemia)
Structural adaptations
Circle of Willis: 2 internal carotid and 2 vertebral arteries, anastomose
Short arterioles, dense capillary network
Relatively high vascular resistance
Cerebral perfusion maintained if carotid artery obstructed
High capillary density aids gas exchange
Large SA
Reduces diffusion distance
Brain capillary endothelial cell
Tight junctions: not leaky, prevents bulk flow and diffusion of water and ions that’s seen between capillary cells in systemic circulation
Cellular basis of blood-brain barrier
Blood brain barrier
Lipophilic solutes (cerebral capillary permeable): such as O2, CO2, alcohol, nicotine, caffeine
Amino acids pass using transport proteins
Epithelial cells have 5-6x mitochondria as muscle epithelium
When K+ in interstitium increases due to neuronal activity K+ is pumped out by Na+/K+ ATPase regulates K+ concentrations
Cerebral capillaries form tight junctions (no bulk flow)
No vesicular transport
Protects neurones
Maintains environment
Functional adaptations
High basal flow- high O2 extraction
Regulation of other organs safeguards cerebral circulation- peripheral vasoconstriction (except heart) can maintain arterial pressure therefore cerebral flow
Autoregulation well developed between 60-150mmHg
Resistance vessels dilate at low pressure to maintain optimal flow and constrict at high pressure
Below 60mmHG- mental confusion and syncope
Cerebral vessels are very responsive to arterial CO
Hypercapnia (high PaCO2> 5KPa) induces vasodilation cerebral vessels
Useful during asphyxia to maintain O2 delivery
Endothelial NO and Fall in myocyte pH mediate vasodilation
Small pial arteries dilate more than larger cerebral arteries in response to CO2
Hypocapnia (low PaCO2<5kPa) causes vasoconstriction will 1/2 cerebral flow
Responsible for dizziness during hyperventilation
Cerebral vessels are less responsive to levels of arterial O2
Hypoxia (low PaO2)
Moderate hypoxia evokes little change in cerebral flow
Severe hypoxia leads to vasodilation- adenosine, K+, NO so systemic hypoxia only has minor overall affect on cerebral flow.
Will evoke hyperventilation through stimulation carotid chemoreceptors- fall in arterial CO2–cerebral vasoconstriction
Systemic hypoxia evokes hyperventilation so hypoxic vasodilation often masked by hypocapnic vasoconstriction
Neuronal activity-evoked functional hyperaemia
Factors important in coupling tissue metabolism to local flow:
-neuronal activity increased potassium permeability membranes, increase interstitial K+
-adenosine (metabolic messenger)
-neuronal nitric oxide
-metabolites released from astrocytes during increased activity
-CO2, increased levels can cause vasodilation
Flow shifts with mental focus to keep net cerebral flow constant
Is nervous control important in determining cerebral flow
Maximal sympathetic stimulation increases resistance by only 20-30%
Baroreceptors have little influence on cerebral flow
Sympathetic stimulation shifts autoregulatory curve to right: to protect brain from damaging effects elevated pressure, this will make individual more susceptible to reduced perfusion if BP falls below lower end of autoregulatory range
Autonomic nerves have little effect on cerebral flow
Vascular problems
Raised intracranial pressure ICP
3 intracranial constituents: tissue, blood, CSF
ICP raised by:
-intracranial bleeding
-cerebral oedema
-tumor
Increased ICP:
-collapses veins
-decreased effective CPP
-reduce blood flow
Cerebral perfusion pressure: mean ABP-ICP (normally 0-10)
Postural syncope if baroreflex/autonomic activity impaired eg ageing, neuropathy
Transient ischaemic attack TIA
Cerebrovascular accident (stroke)
-ischaemic stroke occurs when there’s atherosclerosis or blood in extra cerebral artery
-haemorrhagic stroke- weakened vessel wall ruptures causing bleeding in the brain
Function cutaneous circulation
Provide skin with modest metabolic requirements
Regulate body temperature
Skin is major thermoregulator
Receives ~10% CO
Cutaneous blood flow can vary from 1-200 ml/min/100g
