Special Circulation Flashcards
What is auto-regulation?
Maintain organ blood flow via vascular smooth muscle contraction/relaxation. Specific to brain, kidney, heart. Aldo called Bayless myogenic response/ myogenic response
What is functional sympatholysis?
Where local control of blood flow overrides sympathetic activity. Transient vasoconstriction due to increased sympathetic drive (a-receptors), but followed by vasodilation due to locally released metabolites. Important in skeletal, heart and brain
What is hyperemia?
Increased blood flow in a tissue or organ. Usually due to local control of blood flow
What is metabolic hyperemia?
Increased metabolic activity results in local increases in metabolite concentrations. Metabolites override sympathetic activity (functional sympatholysis). E.g. inhibition of sympathetic mediated vasoconstriction during exercise
Outline sympathetic control of blood flow control
Sympathetic
- post-ganglionic fibers release NE onto target organs
- adrenal medulla releases NE and E into bloodstream
- both act on a1 and a2 adrenoreceptors —> vasoconstriction
- general sympathetic tone provides basal levels of vasoconstriction throughout the circulatory system which contributes to TPR
Outline the impact of parasympathetic influence in blood flow
Minor importance
- post-ganglion fibers release acetylcholine
- ACh mediates vasodilation-this is important in blood vessels of the penile erectile tissue
What is the problem with coronary circulation ?
The coronary circulation receives about 5% of CO at rest, which is considerable given its limited size. O2 extraction from blood is high at about70% at rest. To get more O2 to the h3art blood flow must increase, hence O2 delivery to heart is flow limited
How is coronary blood flow regulated?
Local control (metabolic hyperemia)
- dominant mechanism for regulating coronary blood flow
- working heart muscle releases vasoactive metabolites (NO, adenosine)
Sympathetic control (less important):
- brief vasoconstriction via a receptors
- less important than local control due to functional sympatholysis, I.e. local effects override sympathetic vasoconstriction
Autoregulation
- still debated, appears to operate largely via local metabolic control
- No ckear evidence fir myogenic autoregulation
Describe coronary circulation layout
- O2 is supplied by coronary arteries on epicardium
- heart muscle does not obtain O2 from ventricle /atria lumens
- absence of inter-coronary vascular or collateral vascular connections means that blockage of an artery leads to ischemia downstream of block
- some cope for angiogenesis and collaterization within the myocardium to improve blood supply in long-term ischemic areas of cardiac muscle
What are the mechanical effects on coronary blood flow?
- systole= vascular compression
- diastole= maximal flow
- pressure differences less in right ventricles
How can tachycardia impact coronary blood flow?
- shorter diastole reduces flow
- overridden by metabolic (active) hyperemia(vasodilation)
- oxygen consumption of heart is very high (increased in exercise) relies on oxidative mechanism
Why is metabolic hyperemia important?
Most important for increasing coronary blood flow *adenosine
Coronary blood flow and metabolic activity of the heart must be limked
What are the effects of increasing heart rate on coronary blood flow?
At high HRs duration of diastole is decreased
This leads to decreased coronary perfusion, build up of vasodilator metabolites- ensuring adequate coronary blood flow
O2 consumption of heart very high (increased in exercise). Relies on oxidative metabolism.
Coronary blood flow a d metabolic activity of heart must be tightly linked
What are the effects of exercise on coronary blood flow?
Exercise leads to increased oxygen demand
O2 extraction from blood already high (about 75% at rest )
Increased O2 demand met by increased coronary blood flow
At rest, CBF= 80 ml/100 gm tissue
In exercise= 400
Increased blood flow mediated by metabolic vasodilators (active hyperemia). Response is very rapid
Vasodilators: adenosine, NO, K+, and H+
What is the role of sympathetics in coronary blood flow?
Symp. NS activated in exercise
Symp. NS- transient coronary vasoconstriction (via a1) AND inotropic and chronotropic (via B1)
This leads to increased metabolic activity—> increased vasodilator metabolites—> metabolic hyperemia—> increased coronary blood flow
Symp. Effects in exercise increase metabolism of the heart which triggers metabolic hyperemia resulting in a functional sympatholysis
Metabolic hyperemia is far more important in regulating coronary blood flow because there is functional sympatholysis
What are the clinical correlates of coronary blood flow?
O2 supply/O2 demand ratio important
O2 supply= CBF x arterial O2 content
O2 demand= myocardial O2 consumption (= CBF x A-VO2 difference)
Decreased O2 supply/ O2 demand=myocardial hypoxia (ischemia)
What are the diseases of coronary circulation ?
Coronary vascular reserve
- difference between max flow via vasodilation and flow at rest
- Disease decreases coronary reserve as arterioles cannot compensate (by dilation) fir shortened diastole and increased metabolic demand
Coronary blood flow reduction
- e.g. with coronary atherosclerosis
- decreased myocardial O2 supply
- effects: myocardial ischemia, angina pectoris(chest pain)
- metabolic switch to anaerobic glycolysis, FFA oxidation
Complete flow back
- rapid nutrient depletion
- infarcts, necrosis
Describe how coronary heat disease leads to ischemic heart disease
Leading cause of death in the west
Result in: sudden death(coronary occlusion)
Progressive weakening of the heart, cardiac failure
Cause: atheromatous plaques in coronary vessels
Due to: poor diet, genetic predisposition
What are the clinical impact of atheromatous plaque?
- Leads to progressive narrowing of coronary artery—> insufficient O2 to meet demands—> cardiac ischemia which leads to both angina and myocardial infarction
- leads to Protrusion through endothelium—> comes into contact with flowing blood—> platelets aggregate fibrin deposited—> thrombus formed—> occlude coronary artery—> cardiac ischemia
What are the symptoms of angina pectoris?
Chest and/or l3ft arm pain
What is angina pectoris?
Triggered when cardiac O2 demand excess supply
- with exercise and coronary atherosclerosis
- with cold and stress via increased sympathetic vasoconstriction
- coronary occlusion: triggered with exercise
- coronary vasospasm: triggered at rest
Indicates Ann underlying insufficiency of coronary vascular reserve
- usually due to narrowed coronary arteries e.g. with atherosclerosis
- ischemic heart muscle releases algogenic (pain generating) substances, e.g. substance P
Pain radiates down left arm because cardiac chemisensitive afferents converge with somatic afferents
-radiating (when pain includes source organ and extends beyond ) versus refferred pain (pain doses not include source organ /area)
What is the goal of angina treatment?
Decrease oxygen demand, of increase oxygen supply
Increase oxygen with surgery- by pass, stents
Decreased oxygen demand with drugs that decrease prel9ad, decrease HR & contractility
What is used to treat angina?
- Decreased oxygen by decreased work load
- decreased work load by decreased contractility, decreased preload, and decreased afterload
Anti anginal drugs
Nitroglycerin: venodilation (and arteriolar dilation)
Beta blockers: decreased HR and contractility
Ca channel blockers: decreased contractility, decreased afterload and preload (vasodilation)
Describe the metabolic needs of skeletal muscle
Has highly variable metabolic needs
, receiving between 18% at rest and 80% during intense exercise of total CO. Tonic, sympathetic mediated vasoconstriction restricts blood flow at rest. High energy demands during exercise are met by increased blood flow due to locally mediated vasodilation
Contrast blood flow in skeletal muscle in rest and contraction
At rest- vasoconstriction
- rich sympathetic innervation mediated basal vasoconstriction
- normal TPR & MAP
- Low concentrations of vasoactive metabolites at rest do notovverrude sympathetic control
During exercise- vasodilation
- functional sympatholysis: local control (active/reactive hyperemia due to vasoactive metabolites like lactate, K+, adenosine) overrides sympathetic vasoconstriction
- massive increase in blood flow to muscle (capillary recruitment)
- TPR & MAP changes depending on static vs dynamic exercise
Contrast dynamic and static exercise
Phasic, dynamic exercise
- e.g. running
- active hyperemia due to metabolites
- blood flow is not interrupted
- capillary recruitment—> reduced local resistance
- sympathetic control maintains global TPR & MAP
Static exercise
- e.g. weightlifting
- sustained contractions block blood flow—> increased local resistance & TPR
- increased TPR abd cardiac output can lead to increased MAP
- vasodilation after contraction due to ischemia and build-up metabolites
- reactive or ischemia hyperemia
What is intermittent claudication?
Pain and cramping in legs during exercise
Caused by peripheral vascular disease due to atheromatous plaques in arteries supplying legs
Describe cerebral circulation
At rest, the cerebral circulation receives about 15% of CO, a large proportion because the human brain has high O2 consumption abd metabolic needs. Local control dominates, sympathetic innervation is sparse
What are the features of cerebral circulation?
Critical circulation, maintained at any cost
- disruption of blood flow for seconds- unconsciousness
- for minutes- irreversible brain damage, death
- Circle of Willis: interconnecting arterial vessels safety mechanism fir cerebral perfusion, especially if an artery occluded
Brain requires glucose as energy source
- ketones can also be metabolized during starvation
- some cells, e.g. retinal photoreceptors, can only use glucose as they do not have mitochondria
Mechanical effects: increased intracranial pressure—> decreased blood flow
Vasoactive metabolites: CO2, H+ (pH), adenosine
Explain autoregulation in cerebral circulation
Blood flow remains at constant at pressures 60-180 mmHg
Due to autoregulation (bayliss myogenic response)
Less than 60 mmHg—> decreased perfusion —> confusion, unconsciousness
Chronic high blood pressure shifts autoregulation curve to right, maintaining blood flow at higher pressures
What is the impact of PO2 in cerebral circulation ?
-Large drop in PO2(hypoxemia) required fir significant increases in blood flow (below 50 from normal 95 mm.Hg)
What is the impact of PCO2 in cerebral circulation?
- blood flow sensitive to small changes in PCO2
- PCO2 alters pH via formation of carbonic acid, sensed by chemoreceptors
- Increased PCO2 (hypercapnia)—> vasodilation
- Decreased PCO2 (hypocapnia)—> vasoconstriction
What are the key roles of control mechanisms ?
- central perfusion (whole brain):
- (bayliss) myogenic autoregulation
- regional changes
- metabolic hyperemia is dominant control mechanism
- regional increased in neuronal activity —> increased oxygen demand
- metabolic hyperemia links blood flow to metabolic demand
- astrocytes are important in ‘neurovascular coupling’
- research use: BOLD fMRI infers neuronal activity by measuring local blood oxygen levels
Sympathetic control:
- minimal effect on cerebral blood flow
- sparse sympathetic innervation in cerebral arterioles and arteries
What is the key determinant if cerebral blood flow?
CPP (Cranial perfusion pressure)= MAP - ICP
Not MAP - CVP (central venous pressure) as in other tissues
Not elevated ICP, e.g.m due to TBI( concussion), is very dangerous
What increases intracranial pressure?
ICP increased by:
-intracranial bleeding
- cerebral edema
- tumor
What does increase in ICP cause?
- collapse veins
- decreases effective CPP reduces blood flow
Describe pulmonary circulation
All of CO enters the pulmonary circulation. Local control of blood flow is most important, sympathetic control least important. Mechanical effects due to lung inflation also play a role
Differences to other circulations
- low pressure (8- 20 mmHg at rest)
- low resistance to flow
- receives 100% cardiac output (CO), from right ventricle
Hypoxia causes local vasoconstriction in the lungs
- purpose of lungs is to oxygenate blood
- blood flow is optimized to alveolar regions rich in oxygen by reducing flow to poorly oxygenated alveoli
- vasoconstriction around oxygen-poor alveoli via O2 sensing K+ channels (Euler-Liljestrand mechanism)
Vasoactive metabolites also cause vasoconstriction in hypoxic alveoli
Summarize cutaneous circulation
Skin has a relatively constant, low metabolic rate, receiving about 4% of CO at rest (1-60% with extreme cold/heat). Oxygen needs are easily met by low blood flow, increased blood flow is most important for temperature regulation
How is cutaneous circulation controlled?
Sympathetic control (most important): -Arteriovenous (AV) anastomoses are bypass vessels between cutaneous arteries, and veins, Innervated by adrenergic sympathetic fibers
- vasodilation of AV shunts allows blood to enter venous plexuses without having to pass through the skin surface capillaries, thus reducing heat loss
- key for temperature control
- flow through AV shunts can range from 0 to 1 L/min, severely reducing TPR and MAP
Local control (weak):
- temperature
- weak reactive hyperemia
- weak autoregulation
Explain cutaneous thermoregulation
Normothermic conditions
-low skin blood flow (about 5% of cardiac output)
During cold stress
- increased sympathetic vasoconstrictor activity (cutaneous vessels )
- reduced skin blood flow improves thermal insulation
During heat stress
- increased sympathet8c cholinergic vasodilator activity
- increased skin blood flow, can reach 60% of CO!
- allows more heat dissipation as high skin blood flow delivers heat to the skin surface
- cutaneous pooling out of blood due to heat exposure without sufficient acclimatization can reduce MAP dangerously
- can induce syncope (fainting) and ischemic damage in O2^- sensitive organs like intestines
Explain skin blood flow responses to cold stress and heat stress in nonglabrous skin
- under nonthermic conditions, skin blood flow is relatively low (approx. 5% of cardiac output ) and skin vessels receive relatively minor neural inputs from active vasoconstrictor and vasodilator nerves
- During cold stress, reductions of skin and internal temperatures lead to reflex increases in sympathetic nonadrenergic vasoconstrictor nerve activity. Increased vasoconstrictor system tone reduces skin blood flow, th7s increasing thermal insulation and conserving body heat.
- During heat stress, increasing skin and internal temperatures lead to reflex increases in sympathetic cholinergic sudomotor activity. Increased activity of the vasodilator system leads to potentially dramatic increases in skin blood flow that can reach 60% of cardiac output. High skin blood flow delivers heat to the skin surface where it is removed to the environment primarily through evaporation of sweat
Summarize neural controls of thermoregulation effectors in human skin
- thermoregulation reflexes are mediated by the afferent inputs 9f internal and skin temperature
- These afferent inputs are integrated in the preoptic anterior hypothalamus and spinal cord areas of the central nervous system
- Efferent control of blood vessels and sweat glands in glabrous skin is mediated by nomadrenergic vasoconstrictor nerves and cholinergic sudomotor nerves, respectively
- In nonglaborous skin regions, efferent control of blood vessels is effected through a system of dual sympathetic innervation, nor adrenergic active vasoconstrictor nerves and cholinergic active vasodilator nerves
- Sweat glands also receive cholinergic sympathetic innervation; however, whether cholinergic sudomotor nerves are one and the same is not known
