Lecture 11: Special Circulations

Resistance

Blood flow and distribution are regulated by _________________ in the arterial microcirculation

Arterioless

-vessels that regulate bulk flow

Precapillary Spincters

-regulate number of perfused capillaries for exhchange

-affect oxygen extraction

Cardiac Output (CO)

the quantity of blood pumped into the aorta per unit time and is the sum of all factors that control tissue perfusion

Acute Control

-control of flow

-rapid changes in vessel diameter (autoregulation)

Long-term Control

-control of flow

-slow, progressive changes in vessel and number

seconds to minutes

time span of acute regulation of blood flow

Baroreceptor Reflex

The primary reflex pathway for homeostatic control of blood pressure

Decreased

low blood pressure leads to _______________ baroreceptor firing

Decreased

_____________________ parasympathetic outflow leads to increased heart rate and contractility

Decreased; increased

Low BP and decreased baroreceptor firing leads to _________________ parasympathetic and _____________________ sympathetic outflow

Norepinephrine and Epinephrine

Increased Sympathetic Flow results in release of __________________ and ________________________ from adrenal gland

Arginine Vasopressin (AVP)

a peptide hormone from the posterior pituitary that promotes water conservation

Atrial Natriuretic Peptide (ANP)

A hormone, secreted by the heart, that normally reduces blood pressure, inhibits drinking, and promotes the excretion of water and salt at the kidneys.

Decreased

low blood volume results in __________________ atrial filling and myocyte stretch

Vasodilation

Vasodilation or Vasoconstriction?

-smooth muscle relaxation

-resistance decreases

-blood flow increases

Vasoconstriction

Vasodilation or Vasoconstriction?

-smooth muscle contraction

-resistance increases

-blood flow decreases

Compresses

high pressure in surrounding tissue ______________________ vessels

Distends

Low pressure in surrounding tissue _________________ vessels

Myogenic Response

Increased intravascular pressure causes active _____________________________

remains relatively constant

As pressure increases, resistance increases, and Flow __________________________

remains relatively constant

As pressure increases, radius decreases,

Wall tension ___________________________

Vasodilator Metabolites

Increased metabolic rate in active tissues promotes release of ______________________________

Vasodilation

Multiple contributors to

metabolic ________________________:

• Adenosine

• decreased O2

• CO2

• H+

• Lactic acid

• Decreased ATP

• K+

• Osmolality

• Arachidonic acid metabolites

Acute

which would be an example of hypertensive crisis?

Long term

which would be an example of chronic HTN

Pressure-Flow Autoregulation

Intrinsic ability of a vascular bed to regulate its own flow over a wide range of intravascular pressures

Reserve

-The capacity for increasing flow within a bed at any given pressure

-No additional capacity to increase flow

Reserve

Autoregulatory Range

60-140 mmHg

range where flow is independent of pressure due to autoregulation

Endothelial-derived relaxing factors

EDRF

Endothelial-derived constriction factors

EDCF

Endothelial-derived hyperpolarizing factor

EDHF

Myoendothelial Junction

-communication between endothelium and smooth muscle cells

-gap junctions can be found here

-Prostaglandins

-EDHF

-Nitric Oxide (NO)

Substances synthesized by endothelial cells lining the blood vessels that when released, alter the degree of relaxation or contraction of vascular smooth muscle

Vasodilation

Lipophilic gas released from endothelial cells in response to stimuli to cause ___________________

NO

viscous flow of blood (or some vasoconstrictors, ANG II) causes shear stress on vascular walls that contorts endothelial cells to induce _______ release

M3

receptor for parasympathetic dilation of vascular smooth muscle

α1

recepor for sympathetic constriction of vascular smooth muscle

Histamine

• Causes arteriolar dilation and venous constriction

• The combined effects cause ↑Pc and increased filtration out of the capillaries resulting in local edema

• Released in response to tissue trauma

Bradykinin

• Causes arteriolar dilation and venous constriction

• Produces increased filtration out of capillaries and local edema

Serotonin

• Causes arteriolar constriction and is released in response to blood vessel damage to help prevent blood loss

Vasodilators

E-series prostaglandins are ____________________

Vasoconstrictors

F-series prostaglandins are _____________________

Vasodilator

Prostacyclin is a ____________________ in several vascular beds

Vasoconstrictor

Thromboxane A2 is a ______________________

Endothelin

• Potent vasoconstrictor, present in endothelial cells via endothelin converting enzyme (ECE)

• Binds to G-protein receptors in VSMCs and endothelial cells

• Formation & release stimulated by Ang II, ADH, thrombin, cytokines, ROS, & shear stress

Endothelin

• Inhibited by endothelial derived vasodilators (e.g., NO), specifically when ETB receptors are bound

• Implicated in pathogenesis of HTN, coronary vasospasm, and HF

• Presence increased with endothelial damage

Endothelial Dysfunction

-Major role in the development of atherosclerosis

-associated with diabetes/metabolic

syndrome, hypertension, smoking, and physical inactivity

-shift to a proinflammatory, prothrombic state with impaired vasodilation

• Involves decreased NO bioavailability

• Impaired flow mediated dilation (FMD); assessed by ultrasound in brachial artery

Hours to Weeks

time span fo long term control of blood flow

Normal

If MAP is chronically elevated over time, local blood flow approaches _____________ despite increased pressure

Vascular Remodeling

-important when metabolic needs change

-arterioles and capillaries can change in number and size to adapt

Vascular Remodeling

1. ↑ in Angiogenic factors & formation of new blood vessels

2. Rarefaction of vessels

3. Development of collateral circulation in response to occlusion

4. Vascular remodeling in response to chronic changes in blood flow or pressure

Vascular Remodeling

Ability to form blood vessels is the defining characteristic of an endothelial cell

Hyperemia

redness of the skin due to increased blood flow

Active Hyperemia

Increased blood flow to a tissue when its energy demands/metabolism increase

Reactive Hyperemia

-Exaggerated flow that occurs after temporary ischemia

-accumulation and washout of metabolites

-continues until O2 debt is repaid

Reactive Hyperemia

Active Hyperemia

Splanchnic Circulation

blood flow through the stomach, small intestine, large intestine, pancreas, spleen, & liver

Splanchnic Circulation

-Vascular supply is highly interconnected & primarily occurs by way of celiac, superior & inferior mesenteric arteries

-Provides collateral pathways, lessens the risk of ischemia in the event of occlusion

No

does the circulatory system distribute splanchnic blood flwo equally to all digestive organs

increases

Blood flow _______________ sequentially as food progresses along GI tract

Liver

what organ is in parallel AND series with other splanchnic organs?

30%

Splanchnic Circulation receives _____% of CO

Constrict

During high sympathetic output (exercise, hemorrhage); splanchnic arteries and veins __________________

Postprandial Hyperemia

Blood flow to GI tract increases 8 fold following meal

Countercurrent Exchange

the exchange of a substance between two fluids flowing in opposite directions

Microvessels in villi

in splanchnic circulation, what vessels branch into numerous capillaries that are highly permeable to facilitate absorption of nutrients from GI tract

15%

Cerebral Circulation receives about _____% CO

Cerebral Circulation

• Averages 50-60 mL/min/100g

• Remains relatively constant (autoregulation)

-neural, myogenic, and metabolic control

vasoconstriction

in cerebral circulation: increase in transmural pressure results in _______________________

Oxidative

(therefore intolerant of ischemia)

describe brain metabolism

Cerebral Circulation

-no lymphatics

• Blood flow highly autoregulated:

• Localized active hyperemia primarily via increased pH

-BBB

Respiratory Acidosis

-hypercapnia (high blood Pco2) cayses global drop in brain pH and global brain hyperemia

Stroke

-any disruption of brain blood flow

-can be ischemic or hemorrhagic

[CO2] & [H+]

If blood flow severely decreases causing cerebral ischemia, local ______________ and _______________increases greatly

Medulla

In the ischemic pressor response, there is stimulation of the sympathetic vasomotor control areas in the _________________

Ischemic Pressor Response

-stimulation of sympathic vasomotor control

-systemic arterial pressure rises as high as the heart can pump to clear out CO2 and H+

-can elevate MAP

-can cause occlusion of peripheral vessels

Ischemic Pressor Response

-operates as emergency pressure control system when cerebral arterial pressure and blood flow decreases to lethal levels

• <60 mmHg, with greatest stimulation at 15-20 mmHg

Cushing's Reflex

-special type of ischemic response resulting from ↑CSF pressure

• Initiates CNS ischemic response that causes the arterial pressure to rise

Ischemic Pressor Response

Aerobic Exercise

Capacity to increase blood flow > 20-fold during __________________

At Rest

At Rest or During Exercise:

• Sympathetic (and myogenic) tone; high

vascular resistance and low flow

• Low O2 extraction

During Exercise

At Rest or During Exercise:

• active hyperemia

• Low vascular resistance and high flow

• High O2 extraction

Cutaneous Circulation

• Sympathetic inputs

• Sympathetic adrenergic

• Sympathetic cholinergic

• Temperature regulation

Vasoconstriction

in cutaneous circualtion, cold results in sympathetic adrenergic response causing __________________

Vasodilation

in cutaneous circualtion, heat results in withdrawal of sympathetic response causing __________________

Sweating/Vasodilation

in cutaneous circualtion, High heat and stress results in sympathetic cholinergic response causing __________________

Right and Left Coronary Artery

Entire blood supply to myocardium derives from ______________________________

5%

Coronary Circulation receives ______% of CO

Coronary Circulation

• Averages 70 mL/min/100g

• Work of heart can increase 6-9x and coronary flow can increase 3-4x to supply heart

• Adenosine and NO - most important vasodilators here

Resting

In coronary circulation, High O2 extraction under ________________ conditions (70 - 80%) - meet

increased demand by increasing flow.

Adenosine

key metabolic dilator of coronary circulation

Endothelial NO

important for flow mediated filation in coronary circualtion

Sympathetic

___________________ stimulation of the heart increases coronary flow due to increased heart rate, and contractility (active hyperemia).

Endocardium

in reference to coronary circulation, what is susceptible to ischemia due to vascular compression during systole

Left coronary artery

What artery?

Early Systole: isovolumetric contraction of ventricle compresses vessels & aortic pressure is low, reversed flow

Mid-Late Systole: as aortic pressure increases so does coronary

flow, but doesn’t peak

Diastole: ventricles relaxed & aortic pressure still high, coronary

flow is high (~80%)

Right Coronary Artery

Which Artery?

Systole: contributes more flow due to lower wall tension of right ventricle, no reversal

Diastole: virtually negligible augmentation of flow