Vascular Control Flashcards
What is the equation for flow?
Flow = Pressure difference/ resistnace
- Resistance generated in small arteries
- R = 1/radius
- Small changes in diameter can largely and temporarily change blood flow in a vessel
Which organs have the highest oxygen consumption?
- Liver and GI
- Kidney much lower than distribution(filtration)
- Skeletal muscle- increases with exercise
- Heart uses more than blood supply suggests
What is the equation for tissue perfusion?
- Perfusion = pressure gradient/resistance
- Flow takes path of least resistance
- R - 1/r^4
What is the equation for total resistance in the system with parallel vascular beds?
- Total resistance in system = 1/resistance of any given arterial bed
- Each tissue can regulate its own resistance
Describe how exercise effects blood flow to parallel vascular beds
- HR and SV increases
- Amount of blood going to tissues increases
- Regional control is needed- because every vascular bed in every tissue behave the same way
- This is why individual beds are self-regulatory
Describe smooth muscle contraction
- Depolarisation of membrane and opening of voltage gated Ca channels
- Ca influx and Ca induced Ca release from intracellular stores
- Contraction via MLCK activation
- Overlapping of myosin filaments and constriction
Describe activation in smooth muscle
- Agonist-induced increase in Ca through opening of ligand-gated Ca channel or inositol triphosphate
- Diacyl glycerol release of Ca from stores
- No changes in membrane potential
Describe Level 1 intrinsic control
- Mechanical stimuli- myogenic stretch and shear response
- Response of artery to physical force that acts upon them ,autoregulation
Describe Level 2 Intrinsic control
- Local mediators released via cells in vicinity that affect what vascular smooth muscle is doing
- Either constricts/dilates underlying smooth muscle
- Endothelial regulation + other metabolites and autacoids in response to local demands
Describe level 3 extrinsic control
- Systemic regulation (nerve and hormones)
- Sympathetic activation constricts arteries
What parts of the body are primarily intrinsic?
- Brain, kidney and heart
- Local control regulating flow
- Not extremely influenced by what happens globally
- Global change has limited impact on what is happening in brain/heart
Is the skin intrinsic or extrinsic and why?
- Primarily extrinsic
- Blood flow to skin about thermal regulation
- If one is cold, blood flow to skin decreased
- Cool peripheries consequence of low pressure
Is skeletal muscle intrinsic or extrinsic?
- Primarily extrinsic at rest
- During exercise, local metabolites tend to dominate (more local)
Describe the myogenic response of smooth muscle
- Stretch–> contraction
- Exact mechanism unknown- involves increase in intracellular stores
- Seen in many vascular beds (cerebral, renal etc.)
- Arteries always slightly constricted- basal tone, can be in/decreased, stabilises flow and prevents excessive perfusion
- Important in auto-regulation
What are the roles of vascular endothelium?
- Interface btwn blood and body tissues
- Controls blood coagulation
- Regulated vascular structure
- Mediated inflam responses
- Regulates vascular tone
What mediators does vascular endothelium release?
- Nitric oxide
- Endothelins
- Prostaglandins (PGE2, PGI2)- platelet aggregation
What is NO and how is it produced?
- NO produced by NO synthase
- Forms eNOS + nNOS constantly produce NO
- inducible iNOS in smooth muscle and macrophages
- NO- vasodilator released by shear stress and ACH and bradykinin
- Anti-thrombogenic/atherogenic
Describe the NO pathway
- Receptor bind- Ca influx, phosphorylation of eNOS
- Arginine–> citrulline + NO
- Diffuses into lumen preventing platelet aggregation
- Also diffuses down to smooth muscle- activates guanylate cyclase
- Production of cyclic GMP
What disruptions are there to NO pathway?
- Loss of eNOS/Arginine- no NO produced- thrombogenic surface
- Damage of endothelium, reduces NO capacity, increased resistance and generation of a thrombogenic surface
What drugs interact with NO pathway?
- Nitrates, e.g. GTN in angina- act as NO is released via metabolism
- Phosphodiesterase inhibitors (t5), e.g. sildenafil (Viagra) for ED and pulmonary HT, prevents breakdown of cyclic GMP
What other endothelial pathways are there (other than NO)?
- Prostaglandins- NSAIDS, arachidonic acid metabolites
- Prostacyclin, PGI2, PGE2- act of adenylate cyclase- cAMP
- Endothelial-derived hyperpolarise factos hyperpolarise smooth muscle causing relaxation
- important in microvasculature
- K influx
What can endothelial damage lead to?
- Atherosclerosis and hypercholesterolaemia
- Diabetes and metabolic syndrome
- Smoking
- Hypertension/ preeclampsia
- Ageing and menopause
- Less relaxation and more platelet aggregation
Describe metabolites in vascular control
- Number of waste products- some vasoactive
- Increased CO2, K, H+ and adenosine and O2 promote vasodilation
- Acidity- dilates muscle
- Adenosine- go up when O2 levels fall and insufficient ATP made- drives relaxation of vascular system-> promotes dilation and perfusion
- Increased oxygen consumption and metabolism decreases resistance and drives increased perfusion
What is metabolic hyperaemia?
- Increased metabolic rate in tissue- increases O2 turnover
- Accumulation of metabolites- CO2, H+, K+, adenosine
- All O2 consumption will produce more CO2- acidity
- Local vasodilation, lowered resistance increases flow
- Accumulated metabolites flushed out
- Appropriate blood flow to match metabolic rate
What other autocoids are there?
- Produced by many cells- local action
- Released by cells near vessels- immediate impact
- Pathological (e.g. inflammation)
- E.g. histamine, bradykinin, serotonin, eicosanoids and prostanoids (prostaglandins, thromboxanes, leukotrienes)
- Mixture of dilators and constrictors
Describe extrinsic neuronal/hormonal control
- Vascular system mainly SNS (central control)
- Increases HR + SV, vasoconstriction via α-1 adrenoceptors
- PNS less common along with other sensory fibres
- Very few arteries
- Number of hormones are also vasoactive- either constrict or dilate vessels
Describe vasoconstrictor fibres
- Sympathetic- vascular tone
- Drive slight constricted level of arteries
- NA- α-1 adrenoceptors
- Increased symp activity increases vasoconstriction
- Symp cholinergic- ACh
- PNS mediated by ACh and some non- adrenergic/ cholinergic transmitters
- Nociceptive C-fibres mediated by neuropeptides such as CGRP
- Not all sympathetics
What are huge indicators of sympathetic activation?
- Cold clammy peripheries
- Tachycardic, tachypnoeic
Describe vasoactive hormones
- Adr from adrenal medulla
- Part of sympathetic activation, NA acts at α, and Adr at β
- Predominantly dilatory
- Constriction/ dilation is vascular bed dependent
- Ang II acts on AT receptors potent vasoconstrictor
- Vasopressin (ADH)- vasoconstrictor
- Insulin and oestrogens- dilator
