Local Control Of Blood Flow Flashcards
What determines blood flow?
Tissue metabolic need
Increased metabolic activity correlated well with increased blood flow
Individual organs regulate own blood flow according metabolic requirements
What are the 2 factors affecting local control of blood flow?
Extrinsic Tone- TPR HR MAP= CO * TPR Controlled by nerves/hormones
Intrinsic/local control
Flow to organ capillaries controlled by arteriole vasoconstriction. Independent of nerves/hormone
Intrinsic/local control
-most impt in renal, cerebral and coronary
Less so in skel muscle
Little to none in skin
Summarize metabolic control of blood flow
- Metabolic (Active, functional) hyperemia
- Reactive (post-ischemic) hyperemia
Increased tissue metabolism—> increased release of vasodilator metabolites, endothelial secretions and paracrines—> vasodilation of blood vessels—> increased blood flow —> increased supply of oxygen, and nutrients as long as metabolism is increased
What is metabolic (active) hyperemia?
Increase in blood flow to an organ due to an increase production of vasodilator metabolites and endothelial secretions
Explains the increase in blood flow to skeletal and cardiac muscle during exercise
Describe reactive (post-ischemic) hyperemia
Temporary occlusion of a blood vessel—> build up of metabolites downstream of the occlusion—>vasodilation downstream—> increased blood flow
The longer the period of occlusion the longer the subsequent hyperemia
Describe myogenic control of blood flow
Blood flow is indirectly proportional to MAP (Bulk flow or Darcy’s law)
If MAP rises, blood flow is expected to increase
But between MAP of 60/80-160 mm Hg there is NO appreciable increase in blood flow (flow regulated)
Myogenic response. It is responsible for autoregulation of blood flow.
- stretch of blood vessel wall (by increased pressure)
- contraction of the smooth muscle of resistance arterioles
- decreased radius, increased resistance
- keep blood flow constant
What is the myogenic response for decreased blood pressure?
If blood pressure drops (moves to left)-vasoconstriction to reduce flow
If blood pressure increases (moves to right)-vasoconstriction to reduce blood flow
Important kidney and brain
Where is autoregulation most important?
Autoregulation most important in resistance arterioles of:
- cerebral circulation
- renal circulation
What is the function of autoregulation in myogenic control?
Safeguards blood flow to individual organs when BP falls
Stabilizes capillary perfusion pressure (prevents edema should BP rise)
What are the metabolic vasodilators?
Adenosine
H+
Low PaO2(hypoxia)
Interstitial K+
How is adenosine metabolic vasodilator?
Formed from AMP (particularly in skeletal and cardiac muscles). Good correlation between metabolic rate in cardiac muscle, adenosine content and coronary blood flow. (In renal constrictor)
How is H+ a metabolic vasodilator?
Cerebral blood vessels very senstive change PCO2 and [H+]. Arterial pCO2 important regulator of cerebral blood flow.
How is low PaO2(hypoxia) a metabolic vasodilator?
PaO2 normally about 100 mm Hg. PaO2<40 mm Hg—> vasodilation increase in blood flow helps to restore the oxygen supply to the tissue. Exception: lungs -hypoxia constrits pulmonary vessels
Why is interstitial K+ a metabolic vasodilator?
Skeletal muscle & brain activity—> increased K+ with increased action potentials. Skeletal muscle [K+]o increase from 4 mM —> 9mM. Increased K+ —> paradoxical relaxation of Vascular smooth muscle-(vasodilation) and increased blood flow
What is reactive (post-ischemic) hyperemia?
Hypoxia
Hypoxia —> vasodilation
- activation of different K+ channels (KATP and Kir).
- hyperpolarization abd L-type Ca2+ channel closure
-Vascular myocytes (smooth muscles) relax in hypoxia
Explain the paradoxical effect of hyperkalemia
Hyperkalemia due to increased activity of cardiac/skeletal muscles- local increases in K+ ions. Local control of blood flow via vasodilation of smooth muscle (active hyperemia)
Most cells: hyperkalemia reduces driving force, thus decreased K+ efflux and membrane depolarization
Paradoxical effect in smooth muscle: depolarization NOT occur! Hyperkalemia reduces driving force BUT opens special K+ channels! Increased conductance of K+ activated K+ channels offsets reduced driving force. Thus membrane doesn’t depolarize.
K+ activated K+ channels & hyperkalemia
- Channel conductance via channel, and Na/K pump activity increased
- Increased K+ ion efflux, offsets decreased DF, stabilizes Vm near Ek or hyperpolarized cell membrane
Closure of L-type Ca2+ channels
-Smooth muscle relaxation (recall some resting tone exists in vasculature smooth muscle )
Contrast paradoxical effect in smooth muscle and normal cells
In normal cells: Hyperkakemia is an increase in K+ on the outside of the cell . Thus decreases the driving force and causes the RMP more positive. Depolarization can occur even quicker
Smooth muscle: hyperkalemia ow still an increase of K+ on the outside of the cell. This transiently decreases but it’s offset by the special K+ channels
Depolarization dies not occur in this case Because K+ leaves cell via special K+ channels —> hyperpolarization —> vasodilation
Explain endothelial control of blood flow
Paracrine agents: endothelial cells secreted and act on adjacent myocytes.
Prostacyclin (PGI2) Vasodilator
- a prostaglandin
- inhibits platelet aggregation
- produced in response to thrombin
Both NO (or EDHF) and prostacyclin limit spread of platelet aggregation and prevent uncontrolled vascular thrombosis
NO- vasodilator (formerly endothelium derived hyperpolarizing factir(EDHF) or EDRF; R= relaxing
Main stimulus for NO production= shear stress at endothelial cell (detected by glycocalyx on endothelial lumen)
Stimulates guanylyl Cyclase —> increased cGMP—> vasodilation
Continually modulates basal vascular tone
Responsible for:
- flow induced vasodilation of exercise
- vasodilation of erection
- vasodilation of infkammation
What hormones are involved in endothelial control of blood?
Circulating hormones
Paracrine hormones
Shearing forces
Hypoxia
E.g, acetylcholine, bradykinin, histamine via H1receotirs, VIP, substance P
Describe endothelin control of blood flow
Endothelin (ET-1)-vasoconstrictor
Contributes to basal vascular tone
Associated with pathological states
Increased endothelin levels found in:
- Hypoxia: partly responsible fir pulmonary hypertension seen at high altitudes.
- Preeclampsia (acute hypertension of pregnancy)
- cardiac failure: may contribute to the characteristic renal and peripheral vasoconstriction
- Strokes: levels are increased in the CSF following subarachnoid hemorrhages, brain injury. Contributes to cerebral vasospasm
Migraines: likely increase cerebral pressure abd play a role in migraines
How does NO activate smooth muscle relaxation ?
Paracrine activity of NO
- ligand act on endothelial cells
- NO generated via NO synthase activity on L-arginine
- NO diffuses to vascular SM cell
- Increased cGMP
- decreased Ca2+ concentration
- relaxation of vascular smooth muscle
- vasodilation
What is the role of NO in inflammation and endotoxins shock?
Results from specific activation of inducible NOS (iNOS) , which has higher activity than endothelial NOS)eNOS)
Inflammatory response: bradykinin, substance P, thrombin activate both endothelial NOS (eNOS) and inducible NOS(iNOS) (increased NO)
bacterial response: stimulates monocytes and macrophages release of interferon-gamma- a potent stimulator of iNOS (increased NOS)
-Can result in severe hypertension- endotoxin shock
How can angina be treated?
Angina pectoris- poor blood flow to the heart
Nitrate drugs: nitroglycerin (glyceryl trinitrate), generates NO via aldehyde dehydrogenase. (Also used as an explosive)
What is the mode of action of nitroglycerin/ glyceryl trinitrate in treating angina?
Increased cGMP—> vasodilation (venodilation> arteriolar dilation)
Venodilation leads to decreased CVP which leads to decreased preload (EDV) which then leads to decreased SV
Decreased S., decreases oxygen demand of heart muscle
Uses: angina pectineus- poor blood flow to heart
What is the significance of Thromboxane as a vasoconstrictor?
Prostaglandin: thromboxane A2(vasoconstrictor): platelets from aravhifknic acud via COX. Involved in clotting and helps to stop bleeding. Inappropriate platelets activation —> thromboxane release can cause coronary vasospasm
Clinical box- thrombosis: clot within blood vessel
Thromboxane—> platelet aggregation
Aspirin (in low doses) inhibits Thromboxane formation in platelets
Aspirin—> prevent thrombosis in coronary atheroma
What autocoid vasoconstrictors act through paracrine control of blood flow?
Serotonin 5HT (vasoconstrictor)
Prostaglandin (vasodilator/vasoconstrictor )(discussed I’m endothelial section
What us function of Serotonin 5HT (vasoconstrictor) ?
Paracrine blood flow- from platelets during clotting- vasoconstriction (stops the bleeding ).
Coronary circulation: atheromatous coronary arteries: inappropriate platelet activation—> 5-HT release can cause coronary vasospasm
Cerebral circulation: partly responsible cerebral vasospasm (migraine, following a subarachnoid hemorrhage)
What autocoids act as vasodilators in paracrine control of blood flow?
NO
Histamine (vasodilator): from mast cells —> inflammatory response. Dilated arterioles and constricts veins and increase venular permeability. Redness abd edema of inflammation
Bradykinin (vasodilator ): stimulates nociceptors abd is a potent algogen (pain producer). Via nitric oxide (NO)
Prostaglandin: prostacyclin/PGI2, PGE2 (vasoconstrictors): released from endothelial cells
What is the sympathetic effect on blood flow?
Tonic sympathetic activity on blood vessels—> partially constructed
Decreased sympathetic activity—> vasodilation
Increased sympathetic tone—> vasoconstriction
Sympathetic tone in one organ can be regulated independently of other tissues
Describe parasympathetic activity
Limited distribution to blood vessels
Release ACh which binds to muscuranic receptors
Activation of M receptors —> increased NO —> vasodilation
Contrast the effects of epinephrine and norepinephrine on blood flow
Plasma conc. EPI: B2 - vasodilation, increased. HR, decreased TPR, increased CO, little change in MAP
NE- vasoconstriction a1, increased HR
Acts on a1 and B1 receptors
On graph, transient increase in HR (B1 receptors)
HR later decreases (baroceptor reflex)
What is the main differentiation in epinephrine and nkrep?
Epinephrine can cause BITH vasodilation and vasoconstriction
Differential action of epinephrine on a and B receptors due to concentration
At normal plasma concentrations of epinephrine: preferentially binds B2 receptor—> vasodilation (in liver/ skeketal muscle), increased HR, and decreased TPR
Drug concentrations epinelhrine (higher than physiological ): preferentially binds a1 receptor—> vasoconstriction
(And at normal concentrations is causes vasoconstriction skin abd splachnic/gut circulations)
Differentiate intrinsic and extrinsic regulation
Intrinsic- autoregulation- control of LOCAL blood flow at local/ organ arteriole level. Satisfy tissue/ organ metabolic demand
Extrinsic regulation- mainly concerned with control of mean arterial pressure (MAP) and TPR. Maintain blood pressure to ALL parallel arteries for tissue/organ perfusion
