P: Regional circulation Flashcards
Resting coronary blood flow:
around 225ml/min
What is active hyperemia?
vasodilatory metabolites released when levels of O2 in coronary myocytes becoming insufficient.
Mediators of active hyperemia and their respective mechanisms?
adenosine and nitric oxide.
Reduction in [ATP]I results in an opening of K channels + hyperpolarisation –> relaxation of vascular smooth muscle.
Direct effect of sympathetic nerves on blood vessels :
Vasoconstricts via alpha adrenergic receptors on coronary VSM
Indirect effect of sympathetic nerve activity:
increased cardiac activity produces metabolic vasodilatory metabolites –> increases coronary blood flow. So indirectly causes vasodilation.
Myocardial infarction:
- Decreased cardiac output
- Pulmonary oedema from buildup of blood
- Fibrillation of heart
- Rupture of heart
Basal high SN activity:
- Maintains degree of vasoconstriction
- Binds to a and adrenergic receptors on VSM
- Modulated by baroreceptors
Carotid artery occlusion
- Reduces baroreceptor firing
- Increases SN activity immediately reducing muscle blood flow
- Contributes large increase in MAP
Release of carotid artery
- Increases baroreceptor firing
- Vasodilation caused by reduced SN activity increase muscle blood flow
- Reduction in MAP
Vasodilatory metabolites
Adenosine, K+, CO2, lactic acid. Increase blood flow in active muscle.
VSM in exercising skeletal muscle in response to adrenaline concentration changing:
At start of exercise, low adrenaline concentrations only bind to B1 and B2 receptors, causing vasodilation and increased blood flow to skeletal muscle.
As exercise gets more intense, adrenaline starts binding to a-adrenergic receptors, producing vasoconstrictor effects.
ACh relation to nitric oxide
- Ach can trigger nitric oxide release from endothelial cells
- Activates endothelial nitric oxide synthase
- Endothelial mediated regulation of blood flow
Early stage of exercise
- Ach from neuromuscular junction may also diffuse to local blood vessels promoting NO production, VSM relaxation + vasodilation
- Metabolites in actively contracting muscle induce dilation in microcirculation promoting a pressure gradient with upstream feed arteries.
- Increase in blood flow elevates shear stress, release of NO and further vasodilation
Nitric Oxide during exercise
- NO can cause function sympatholysis –> vasoconstrictor activity blunted as NO inhibits noradrenaline release + opposes a2-mediated constriction of VSM
- Skeletal muscle fibres contain neuronal NOS which increase NO release during contraction which can promote local vasodilation.
Cutaneous circulation:
- Arterioles feed blood into capillaries which loop under epidermis
- Blood flows into complex venous plexus which acts as blood reservoir
- Specialised shunts, arteriovenous anastomoses feed blood into plexuses directly from subcutaneous arteries.
Cutaneous circulation regulation:
- Requirement for O2 and nutrients is low - circulation is mainly needed to regulate body temperature
- Regulated by SN activity: vessels express mostly a-adrenergic receptors
- At normal temperatures skin circulation is subject to a high degree of adrenergic tone.
- Increase SN activity: vasoconstriction of arterioles and AV anastomoses –> reduction of flow into skin capillaries
- Inhibition of SN: vasodilation, increased blood flow.
Reactive hyperaemia:
increased blood flow following ischaemia –> vasodilatory metabolites.
Effects of exposure to cold:
- Vasoconstriction of capacitance vessels at that region & other extremities
- Temperature receptors signal to temperature regulating centre of hypothalamus, stimulates SN activity to skin
- Diverts blood from extremities
- With sustained exposure, initial vasoconstriction is following by localized cold vasodilation –> warm blood flows in and skin becomes flushed
Cholinergic sympathetic nerve innervations:
innervate sweat glands + stimulate sweat production during exercise/ in response to heat
What is bradykinin?
- Produces by sweat
- Potent vasodilator
- Stimulates formation of NO
- Perspiration and increased blood flow to skin happen simultaneously
Effects of exercise increasing sympathetic outflow:
- Initial vasoconstriction, diversion of blood to active muscles
- Cholinergic sympathetic promote perspiration + vasodilation
Countercurrent heat exchange:
Arteries and veins are very close, so cooled venous blood returning from cold hand can be warmed by arterial blood; can happen in opposite direction if exposed to heat.
How is blood circulated into brain?
- Internal carotid and vertebral arteries deliver blood via basilar artery to circle of Willis, which loops around brainstem
- Cerebral arteries carry blood to brain tissue
Intracranial pressure increased by:
- Intracranial bleeding
- Cerebral oedema
- Tumour
Effect of increase intracranial pressure:
- Collapses veins
- Decreases effective cerebral perfusion pressure
- Reduces blood flow
Cerebral perfusion pressure equation:
MAP-ICP
Effect of less than 60mmHg in brain
Fainting
Effect of more than 160mmHg in brain
Damage to BBB, can cause cerebral oedema
How does CO2 regulate cerebral blood flow:
- Most important vasodilatory factor
- Increases in CO2 elicit large increases in cerebral blood flow
- CO2 can diffuse across BBB and reduce pH of cerebrospinal fluid
- Reduction of pH triggers vasodilation of cerebral arterioles
Reduction in CPP also reduces washout of CO2 from brain.
Hypercapnia vs hypocapnia
Hypercapnia = increased Pco2
Hypocapnia = decreased pco2
ICP > MAP
severe cerebral ischaemia
Cushing reflex
Response to increased ICP and decreased cerebral blood flow.
1. Cerebral ischaemia stimulates sympathetic system: a-adrenergic receptors binding causes vasoconstriction of blood vessels –> hypertension. B-adrenergic receptor binding increases HR.
2. Hypertension stimulates baroreceptors –> parasympathetic system decreases HR = tachycardia.
3. Hypertension causes irregular breathing.
Cushing’s triad:
Hypertension, bradycardia + irregular respirations –> symptoms in a patient with brain trauma & increased ICP.
Intestinal circulation
- Extensive vascular network which supplies all layers of GI tract down to tips of villi
- Countercurrent exchange of O2 from arterioles to venules in villi
- Blood is shunted directly from arterioles to venules at base of microvilli - reduces O2 supply to mucusal cells at tip and can result in necrosis of villi
Regulation of intestinal blood flow:
- Increased by functional hyperaemia (increase in functional activity of tissue increases blood supply)
- Digestive hormones such as gastrin have vasodilatory properties
- Absorption of biomolecules in GI increases metabolic activity of tissue
- Adenosine levels increase –> vasodilation
- NO produced locally
- Parasympathetic nerves only innervate intestinal SM and glands to increase motility and secretions .
Hepatic circulation:
- Liver receives 25% of cardiac output
- Portal venules and hepatic arterioles enter centre fof acinus and deliver blood into capillary network (sinusoids)
- Sinusoidal capillaries are very leaky, permitting rapid exchange
- Sinusoids radiate to periphery of acinus and connect with hepatic venules, veins and inferior vena cava.
What are ascites and how do they occur?
- Heart failure results in an increase in CVP
- Increases hepatic venous + hepatic sinusoidal pressures
- Increased hydrostatic pressure and hepatic oedema –> accumulation of fluid in abdominal cavity (ascites)
- Can occur as a consequence of liver cirrhosis which causes portal hypertension.
Intrinsic mechanisms to control blood flow:
- Myogenic regulation
- Endothelial-mediated regulation
- Metabolic regulation
Extrinsic mechanisms to control blood flow:
- Neural (sympathetic)
- Hormonal (adrenaline)
