P: Regional circulations Flashcards
What increases O2 delivery to myocardial cell?
Increasing coronary blood flow –> supply is flow limited
Increase in cardiac activity triggers a corresponding increase in ___
coronary blood flow
- Driving force is provided by ____.
- Rate of blood flow determined by ____.
- aortic pressure
- constriction/dilation of resistance vessels
____ regulation is the primary controller of resistance of coronary vessels
Metabolic
- Inadequate ____ blood flow, decreased ____ and/or ____ metabolic activity will trigger active hyperemia.
- ____ and ____ are mediators of active hyperemia
- Reduction in [ATP]i results in opening of ____ channels and a ___ –> relaxation of coronary SM
- coronary, arterial O2 content, increased
- Adenosine and nitric oxide (NO)
- K ATP channels, hyperpolarisation
What are the direct effects of stimulation of autonomic nerves on coronary blood flow?
- Direct effects on blood vessels themselves
- Activation of sympathetic nerves: triggers vasoconstriction via alpha-adrenergic receptors on coronary VSM, other coronary vessels express beta-adrenergic receptors (dilation)
- Vagal nerve stimulation slightly dilates coronary resistance vessels
What are the indirect effects of stimulation of autonomic nerves on coronary blood flow?
- Indirect effects result from changes in coronary blood flow caused by changes in the activity of cardiac muscle
- SN activity increases contractility and tachycardia of cardiac muscle –> indirect vasodilation in coronary circulation (increased cardiac activity –> metabolic vasodilatory metabolites –> increase coronary blood flow)
- Vagal activity –> indirect vasoconstriction
- Illustrates primacy of metabolic regulation in coronary circulation
Extravascular compression: contraction of LV slows, halts and temporarily reverses ____.
left arterial blood flow
Blood flow of skeletal muscle is regulated by a combination of ___ and ___ factors.
- At rest: ___
- Exercise: ___
Combination of neural and intrinsic factors.
- At rest: neural regulation
- Exercise: local factors
Resting skeletal muscle: tonic SN activity maintains a degree of ___. Constant ___ release and binding to ____ receptors of VSM in skeletal muscle blood vessels.
- vasoconstriction
- noradrenaline
- alpha1 adrenergic
- Noradrenaline binds ___ and ___ receptors, little affinity for ___ receptors
- Noradrenaline exclusively triggers ____
- alpha and beta1 adrenergic, beta2
- vasoconstriction
- SN activity to skeletal muscle is modulated by ___
- Resistance in skeletal muscle blood vessels contributes a large part of ___
- baroreceptor reflex
- total peripheral resistance
- Carotid artery occlusion reduces ____ –> increased ___ activity immediately reduces muscle blood flow + ___ in MAP
- Release of carotid artery increases ____ –> vasodilation caused by reduced ___ activity greatly increases muscle blood flow + ___ in MAP
- baroreceptor firing, SN, increase
- baroreceptor firing, SN, reduction
What are the vasodilatory metabolites that rapidly increase blood flow in active muscle?
- Adenosine
- K+
- CO2
- lactic acid
Unopposed increased ____ in inactive muscles diverts blood flow to ___ muscles
vasoconstriction, active
- Beginning of exercise, adrenaline (released from ___) has higher affinity for ___ and ___ receptors –> low concentrations of circulating adrenaline preferentially bind ___ receptors —> triggers ___ and ___ blood flow to skeletal muscle
- High concentration of adrenaline: ____ receptors effects predominate –> triggers ____
- adrenal medulla, Beta1 and Beta2, Beta2, vasodilation, increased
- alpha1 adrenergic, vasoconstriction
ACh can trigger ___ release from endothelial cells (potent ___): ACh activates ___
NO, vasodilator, endothelial nitric oxide synthase (eNOS)
Early stages of exercise:
1. ACh spillover from NMJ may diffuse to local blood vessels, promoting ____ production –> VSM ___ and further ____
2. Metabolites in actively contracting muscle induce ___ in microcirculation promoting a ____ with upstream feed arteries –> resultant increase in blood flow elevates ____, release of ____ and further ____
- endothelial nitric oxide (NO), relaxation, vasodilation
- dilation, pressure gradient (ΔP), sheer stress, endothelial-derived NO, vasodilation
During exercise:
- Overall increase in ____ activity, but vasoconstrictor activity in contracting muscles is ___ –> functional ____ (increase activity of a tissue blocks SN activity in the active tissue). ___ may inhibit noradrenaline release from varicosities and also directly opposes ____ of VSM
- Skeletal muscle fibres also contain ____ and contraction increases ____ release –> promote vasodilation locally
- sympathetic, blunted, sympatholysis, NO, alpha2-mediated constriction
- neuronal NOS (nNOS) , NO
What is the technique for measuring limb blood flow called? Explain how it works.
- Venous Occlusion Plethysmography (VOP)
- Venous return from forearm is briefly interrupted by inflating a cuff placed around the upper arm
- Hand circulation = completely occluded with a wrist cuff inflated to > systolic pressure
- Arterial inflow is unaltered –> linear increase in forearm volume overtime (changes in arm circumference + forearm volume measured by a stain-gauge plethysmograph)
- VOP provides a measure of arterial blood flow to that part of the forearm enclosed by 2 cuffs
What’s the main purpose of skin circulation?
Regulation of body temperature
What regulates cutaneous circulation and what do vessels express?
SN activity –> vessels express mostly alpha1 adrenergic receptors (AV anastomoses contract when SN are stimulated, no intrinsic regulation)
What is blushing/blanching caused by?
Blushing: inhibition of SN –> vasodilation of arterioles and AV anastomoses –> increased blood flow to skin in face
Blanching: activation of SN –> vasoconstriction –> decreased blood flow to skin in face
What happens to skin colour following deflation of cuff on arm?
- Inflation occludes inflow of blood into limb
- Deflation –> increased blood flow caused by vasodilatory metabolites –> skin becomes red below point of occlusion (reactive hyperaemia = increased blood flow following ischaemia)
Explain what happens when a region of the body is exposed to cold initially + after sustained exposure and why
Initially:
- Temperature receptors signal to temperature regulating centre of hypothalamus –> stimulates SN activity of skin –> vasoconstriction of resistance/capacitance vessels at that region (local axon reflex) and at other extremities
- Diverts blood from skin at extremities preventing it from being cooled by external cold
Sustained exposure to cold:
- Localized cold vasodilation
- Warm blood flows in skin –> colour becomes flushed (reddening of cheeks)
If coldness persists further: vasoconstriction and vasodilation alternate (local axon reflexes)
Explain what happens when a region of the body is exposed to heat and why
- Heat receptors trigger hypothalamus to inhibit SN activity
- Vasodilation at affected region (local axon reflexes) and at other regions of the body
- Increases flow of warm blood to sub-epidermal circulation –> cooled by proximity to external environment and by perspiration
What stimulates sweat production during exercise/in response to heat?
- Cholinergic sympathetic nerves innervate sweat glands (parasympathetic nerves don’t innervate cutaneous blood vessels)
Sweat production causes an increases in ____, a potent vasodilator
Bradykinin
Bradykinin stimulates formation of ___ –> promotes vasodilation
Nitric oxide (NO)
Exercise causes an overall increase in ____:
1. Initial ____, diversion of blood to ____
2. ___ nerves then promote perspiration/vasodilation as a mechanism to ____
sympathetic outflow:
1. vasoconstriction, active muscles
2. Cholinergic sympathetic , lose heat
Local axon reflexes:
- Sensory nerves activated by ___ and ___ receptors can release neurotransmitters locally
- These act to promote local ___ (skin ___), localised ___ production and pain
- Pain and temperature
- pain and heat
- vasodilation (skin reddening), sweat
Close proximity of major arteries and veins allows ____; cooled venous blood returning from hand is warmed by arterial blood
countercurrent heat exchange
Explain blood supply to brain
- Internal carotid and vertebral arteries deliver blood (via basilar artery) to circle of Willis which loops around the brainstem
- Redundancy in blood: if blockage of a section of the circle –> blood flow from other vessels preserve cerebral perfusion
What’s the equation of central perfusion pressure (CPP)? What does elevated intracranial pressure (ICP) cause?
- CPP = MAP - ICP
- Normally, ICP > CCP
- Elevated ICP (>20 mmHg) reduces CPP –> compression of venous vessels + reduction of blood flow
What is the driving force for brain perfusion?
MAP
Cerebral circulation exhibits autoregulation (myogenic) between ___ and ___ mmHg
60 and 160
What happens to cerebral circulation below 60 mmHg and above 160 mmHg?
- Below 60 mmHg: fainting (syncope) as CPP falls and blood flow is reduced
- Above 160 mmHg: damage to blood-brain barrier –> cerebral oedema
___ factors are paramount in regulating cerebral blood flow
Local
Why does maximum SN activity only increase cerebral resistance by ~20%?
- Metabolic regulation exerts functional sympatholysis (opposition to the stimulation of the SN system)
- Baroreceptor reflex has little effect on cerebral blood flow
____, ____ and K+ regulate blood flow by ____
Vasodilatory metabolites, adenosine, active hyperemia
What is the most important vasodilatory factor in cerebral blood flow?
- Increased production of CO2 by neuronal cells –> increases blood flow
- CO2 diffuses across blood-brain barrier –> reduces pH of cerebrospinal fluid (CSF) –> vasodilation of cerebral arterioles
- Reduction in CPP also reduces washout of CO2 from brain
- Increased PCO2 (hypercapnia) triggers ___
- Decreased PCO2 (hyocapnia) triggers ___
- vasodilation
- vasoconstriction
Explain effect of reduction in O2 on cerebral blood flow
- Initial reduction = not a big effect on haemoglobin oxygen saturation
- PO2 < 50 mmHg = strong vasodilation to maintain O2 supply to brain (rapid activation of SN)
Explain Cushing reflex
- CPP = MAP - ICP
- ICP > MAP –> severe cerebral ischaemia
- Increase in ICP –> shift in brain tissue within skull (herniation)
- Cushing reflex activates SN system –> peripheral vasoconstriction + increase in CO –> increases MAP –> stimulates baroreceptors in carotid bodies –> slows HR drastically (bradycardia)
What is Cushing’s triad?
Hypertension + bradycardia + irregular respirations
In vili there is ___ of O2 directly from arterioles to venules
Countercurrent exchange
What can low intestinal blood flow cause?
- Blood shunted directly from arterioles to venules at base of microvilli
- Reduces O2 supply to mucosal cells at the tip
- Can result in necrosis of villi –> intestinal bleeding
Explain regulation of intestinal blood flow
- SN and intrinsic mechanisms
- Activation of SN –> vasoconstriction of mesenteric arterioles and capacitance vessels via alpha adrenergic receptors –> reduces blood flow to GI tract (especially to villi)
- Occurs especially during exercise (blood diverted to active muscles and heartt)
What are the factors that trigger vasodilation upon ingestion?
- Functional hyperaemia –> increase in blood flow
- Digestive hormones (gastrin) = vasodilatory properties
- Absorption of biomolecules in GI increases metabolic activity of tissue –> adenosine levels increase (vasodilatory properties)
- Breakdown of glucose and fatty acids causes vasodilation
- NO is produced locally to enhance vasodilation
- Parasympathetic nerves only innervate intestinal smooth muscle and glands to increase motility and secretions (may indirectly increase blood flow by stimulating metabolic activity + by producing bradykinin and NO)
- GIT-derived nutrients in portal vein pass from capillaries into liver cells for ___ or reentry into general circulation
- Liver also acts to clear the blood of ___ and ___
- ___ in hepatic artery is required for this metabolic activity
- Another important function of the liver is ____ of blood
- Processing/storage
- Drugs and toxins
- O2
- reservoir
What allows rapid exchange in hepatic circulation?
Leaky capillaries
- Capillaries very ___, lymph fluid has [protein] of 6 g/dl –> oncotic pressure of plasma is ___ in liver
- Hydrostatic pressure in sinusoidal capillaries profoundly affects ___, ____ and ____
- Therefore, ___ is tightly controlled and rates of blood flow in portal venules and in hepatic arterioles are reciprocally regulated
- Porous, low
- Filtration, lymph production and substance exchange
- Hepatic pressure
Explain ascites process
- Heart failure –> increase in central venous pressure (right atrial pressure) –> increases in hepatic venous and hepatic sinusoidal pressures –> increased hydrostatic pressure and hepatic oedema –> accumulation of fluid in abdominal cavity (ascites)
- Also occurs as a consequence of liver cirrhosis which causes portal hypertension
Cerebral vasoconstriction caused by hyperventilation (decrease in ___) results in ___
PCO2, dizziness
- Another important function of the liver is as a ___
- SNS-induced ___ of capacitance venules in the liver can rapidly return half of liver blood to ___ and back into ___ —> occurs during ___ or ___
- reservoir of blood
- constriction, the heart, arterial circulation, exercise, sever blood loos
