L6 - Physiology of Circulation and Pathophysiology of HTN

What are the major functions of the circulatory system?

Deliver O2 and nutrients to tissues; remove CO2 and wastes; transport hormones and WBCs; distribute heat for temperature regulation.

What is the function of the aorta and large conduit arteries?

Transport blood to tissues under high pressure; they have relatively low resistance.

What is the function of small arteries and arterioles?

Control blood flow to tissues by vasoconstriction and vasodilation; they are the major site of vascular resistance and an important site of action for antihypertensive drugs.

What is the function of capillaries?

Exchange nutrients, gases, and wastes between blood and tissues.

What is the function of the venous system?

Return blood to the heart (venous return); veins operate under relatively low pressure.

What are the 3 major layers of a blood vessel from inside → outside?

Tunica intima → Tunica media → Tunica externa (adventitia).

What is the tunica intima?

The innermost vessel layer; contains endothelium that directly contacts blood and provides a slick surface that reduces friction.

How does the endothelium regulate vessel diameter?

Endothelial cells release vasodilators and vasoconstrictors. Healthy endothelium favors vasodilators such as NO; damaged endothelium favors vasoconstrictors such as endothelin-1 and superoxide.

What is the tunica media?

The middle layer containing smooth muscle and elastic fibers; smooth muscle contracts or relaxes to change vessel diameter and regulate resistance, blood flow, and BP.

What is the tunica externa (adventitia)?

The outer layer containing collagen fibers, nerves, lymphatic vessels, and vasa vasorum; it protects, reinforces, anchors, and nourishes larger vessels.

What are vasa vasorum?

Small blood vessels that supply the outer portions of large blood vessels.

What is a myoendothelial junction?

A connection between endothelial cells and vascular smooth muscle through projections and gap junctions; allows direct electrical communication and is common in small resistance arteries and arterioles.

How does membrane potential affect vascular smooth muscle contraction?

Depolarization → Ca2+ channel opening → Ca2+ influx → contraction; hyperpolarization → decreased Ca2+ entry → relaxation.

What directly activates MLCK during vascular smooth muscle contraction?

Ca2+ binds calmodulin → Ca2+-calmodulin activates myosin light-chain kinase (MLCK) → myosin phosphorylation → contraction.

How does nitric oxide (NO) cause vascular smooth muscle relaxation?

NO → guanylate cyclase (GC) → ↑ cGMP → PKG → activation of MLCP → myosin dephosphorylation → relaxation.

Which receptors promote vasoconstriction through Gq signaling?

α1 (epinephrine/norepinephrine), ETA (endothelin-1), AT1 (angiotensin II), and V1 (vasopressin).

Which receptors promote vasodilation through Gs signaling?

β2 (epinephrine), A2 (adenosine), and IP (prostacyclin/PGI2).

What is blood flow?

The quantity of blood passing a given point in the circulation per unit time, usually expressed as mL/min or L/min.

What is laminar blood flow?

Organized flow in which blood velocity is greatest in the center of the vessel and slower near the vessel walls.

What is turbulent blood flow?

Disordered blood flow caused by high flow rate, obstruction, sharp turns, or rough surfaces; turbulence increases resistance.

What is the relationship between pressure, flow, and resistance?

F = ΔP/R. Flow increases when the pressure gradient increases and decreases when resistance increases.

What does ΔP represent?

The pressure difference between two ends of a vessel: P1 − P2. It is the driving force for blood flow.

If ΔP increases while resistance stays constant, what happens to blood flow?

Blood flow increases because flow and pressure gradient are directly proportional.

If resistance increases while ΔP stays constant, what happens to blood flow?

Blood flow decreases because flow and resistance are inversely proportional.

What is blood flow through the entire systemic circulation equivalent to?

Cardiac output (CO).

What is total peripheral resistance (TPR), also called systemic vascular resistance (SVR)?

The total resistance to blood flow throughout the systemic circulation.

What is the relationship between BP, CO, and TPR?

BP = CO × TPR.

How can BP be related to HR, SV, and TPR?

BP = (HR × SV) × TPR because CO = HR × SV.

What are the major factors that regulate vascular resistance and blood flow?

Vessel diameter/radius, blood viscosity/hematocrit, and pressure.

What is Poiseuille's equation for blood flow?

F = πΔPr⁴/(8ηl), where ΔP = pressure gradient, r = vessel radius, η = viscosity, and l = vessel length.

Why is vessel radius extremely important for blood flow?

Flow is proportional to radius⁴, so even a small change in radius produces a very large change in blood flow.

What happens to flow when vessel radius increases?

Flow greatly increases because F ∝ r⁴; vasodilation therefore increases blood flow and decreases resistance.

What happens to flow when vessel radius decreases?

Flow greatly decreases because F ∝ r⁴; vasoconstriction therefore decreases blood flow and increases resistance.

What happens to blood flow when blood viscosity increases?

Resistance increases → blood flow decreases.

How does hematocrit affect blood viscosity and flow?

↑ hematocrit → ↑ viscosity → ↑ vascular resistance → ↓ blood flow.

What happens to blood flow when vessel length increases?

Resistance increases → blood flow decreases because flow is inversely proportional to vessel length.

What is blood flow autoregulation?

A local mechanism that maintains relatively constant tissue blood flow/perfusion despite changes in arterial pressure.

Approximately what arterial pressure range allows effective blood flow autoregulation?

About 70–175 mmHg.

What is the purpose of autoregulation?

Ensure tissues receive adequate nutrients and maintain relatively steady perfusion despite fluctuations in arterial pressure.

What are the major acute mechanisms of local blood flow autoregulation?

Metabolic/vasodilator theory, oxygen lack theory, and myogenic theory.

What are the major long-term mechanisms of local blood flow regulation?

Angiogenesis, increased vascularity, and formation of collateral vessels.

What is the metabolic/vasodilator theory of autoregulation?

↑ tissue metabolism or ↓ O2/nutrient delivery → accumulation/release of local vasodilators → arteriole dilation → ↓ resistance → ↑ blood flow.

Which local metabolites promote vasodilation when tissue metabolism increases?

Adenosine, ATP/ADP, CO2, histamine, K+, and H+.

What is the oxygen lack theory of autoregulation?

Low O2 or nutrients reduce vascular smooth muscle contraction → metarterioles and precapillary sphincters dilate/open → ↑ tissue blood flow.

What is the myogenic response (Bayliss effect)?

↑ intraluminal pressure stretches vascular smooth muscle → smooth muscle contracts → vasoconstriction, helping maintain constant tissue blood flow.

What is the sequence of the myogenic response to increased pressure?

↑ intraluminal pressure → stretch sensor activation → smooth muscle depolarization → voltage-gated Ca2+ channel activation → Ca2+ influx → vasoconstriction → reduction of blood flow toward normal.

Is the myogenic response caused by tissue metabolism?

No. It is an intrinsic response of vascular smooth muscle in the tunica media to stretch/pressure.

What happens when intraluminal pressure decreases during the myogenic response?

Less stretch → less smooth muscle contraction → vasodilation → helps restore blood flow.

How can healthy endothelium promote vasodilation?

Shear stress, ACh, or bradykinin stimulate release of NO, PGI2, and EDHF → vascular smooth muscle relaxation.

How does prostacyclin (PGI2) cause vasodilation?

PGI2 → Gs → adenylyl cyclase → ↑ cAMP → PKA → inhibition of MLCK → smooth muscle relaxation.

How does EDHF cause vasodilation?

EDHF opens endothelial K+ channels → K+ efflux → endothelial-to-smooth-muscle hyperpolarization → ↓ Ca2+ entry → relaxation.

What substances promote endothelial-mediated vasoconstriction in cardiovascular disease?

Endothelin-1 (ET-1), PGH2/thromboxane A2 (TXA2), and superoxide.

How do ET-1 and TXA2 promote vasoconstriction?

Gq → PLC → IP3 → ↑ intracellular Ca2+ → Ca2+-calmodulin → MLCK activation → smooth muscle contraction.

How does superoxide promote vasoconstriction?

Superoxide inactivates NO, reducing NO-mediated vasodilation and favoring contraction.

How can endothelial dysfunction contribute to hypertension?

Damaged endothelium produces/favors vasoconstrictors and reduces NO-mediated vasodilation → ↑ vascular resistance → ↑ BP.

What is angiogenesis?

Formation of new blood vessels in response to long-term tissue blood flow needs.

What are collateral vessels?

Alternate vascular pathways that develop to provide blood flow around an obstructed or inadequate pathway.

How do angiogenesis and collateral vessels affect blood flow long-term?

They increase tissue vascularity/alternate pathways and can reduce vascular resistance and pressure over time.

What primarily provides neural control of blood vessels?

The autonomic nervous system, especially the sympathetic nervous system.

What is the major vascular effect of sympathetic stimulation?

Primarily vasoconstriction → ↑ vascular resistance → ↑ BP.

What is the major cardiovascular role of the parasympathetic nervous system?

Primarily regulates the heart through the vagus nerve → ↓ heart rate and slight ↓ contractility; it has much less direct control over systemic vessels.

Which vessels receive sympathetic innervation?

Most vessels except capillaries, precapillary sphincters, and some metarterioles; small arteries, arterioles, large veins, and the heart are sympathetically innervated.

Why are sympathetic nerves to small arteries and arterioles important?

They can change vessel diameter → change vascular resistance → regulate blood flow and BP.

How can sympathetic overactivity contribute to hypertension?

Excess sympathetic activity causes increased vasoconstriction and vascular resistance, raising BP.

What is the vasomotor center?

A cardiovascular control center in the brainstem that regulates sympathetic vasoconstriction/vasodilation and helps regulate heart function and BP.

What does the vasoconstrictor area of the vasomotor center do?

Excites sympathetic vasoconstrictor neurons → vasoconstriction and increased BP.

What does the vasodilator area of the vasomotor center do?

Inhibits the vasoconstrictor area → decreases sympathetic vasoconstriction.

What does the sensory area of the vasomotor center do?

Receives circulatory sensory information and uses it to regulate the vasoconstrictor and vasodilator areas.

What is the baroreceptor reflex?

A rapid negative-feedback reflex that detects changes in arterial pressure and adjusts autonomic activity to maintain relatively constant BP.

Is the baroreceptor reflex the same as local blood flow autoregulation?

No. Baroreceptors regulate systemic BP through neural reflexes; autoregulation locally regulates tissue blood flow according to local conditions.

Where are the major arterial baroreceptors located?

Carotid sinus and aortic arch.

Which baroreceptors are especially important/sensitive for BP regulation?

Carotid sinus baroreceptors.

What happens in the baroreceptor reflex when BP increases?

↑ BP → ↑ baroreceptor stretch/firing → CNS decreases sympathetic and increases parasympathetic activity → ↓ HR/contractility + vasodilation → ↓ CO and TPR → ↓ BP.

What happens in the baroreceptor reflex when BP decreases?

↓ BP → ↓ baroreceptor firing → CNS increases sympathetic and decreases parasympathetic activity → ↑ HR/contractility + vasoconstriction → ↑ CO and TPR → ↑ BP.

What happens to baroreceptors in chronic hypertension?

They can reset to operate around a higher BP, limiting their ability to correct chronic hypertension.

What is the chemoreceptor reflex?

A reflex in which chemoreceptors detect ↓ O2, ↑ CO2, or ↑ H+ and stimulate the vasomotor center → ↑ sympathetic activity → ↑ BP.

Where are peripheral chemoreceptors located?

Carotid bodies and aortic bodies.

Where are central chemoreceptors located?

In the medulla.

At approximately what BP does the chemoreceptor reflex become important?

When arterial pressure falls below about 80 mmHg.

What is the CNS ischemic response?

Severely reduced cerebral blood flow → CO2 accumulation in the brain → powerful stimulation of the vasomotor center → massive sympathetic vasoconstriction → ↑ arterial pressure.

When does the CNS ischemic response become important?

Generally when arterial pressure falls below about 60 mmHg, with strongest activation at extremely low pressures around 15–20 mmHg.

What is the overall hierarchy of acute BP reflexes as BP falls?

Baroreceptor reflex provides normal moment-to-moment BP control → chemoreceptor reflex becomes important below ~80 mmHg → CNS ischemic response becomes important below ~60 mmHg.