16: Blood Flow and the Control of Blood Pressure

Blood vessel walls

• multiple layers of smooth muscle, elastic connective tissue, fibrous connective tissue, and inner lining (endothelium)

Endothelium

• active tissue

• secretes paracrine signaling molecules

• involved in regulating blood pressure, BV growth, material absorption

tunica intima

• includes endothelium and underlying elastic tissue

• innermost layer of the blood vessel wall

Arteries

• large diameter

• thick walls

• high amounts of elastic tissue and smooth muscle

• moderate fibrous tissue

• small endothelium

• must withstand high pressure

• 
  

Arterioles

• small diameter

• thin walls

• small endothelium

• moderate smooth muscle

Capillaries

• smallest diameter

• thinnest walls

• only endothelium present

• thin to facilitate exchange

• main site for exchange between blood and interstitial fluid

• NO smooth muscle or elastic tissue

Venules

• small diameter

• thin walls

• small endothelium

• moderate fibrous tissue

Veins

• large diameter

• thinner walls than arteries

• moderate elastic tissue

• high smooth muscle

• moderate fibrous tissue

• small endothelium

• thinner walls + more fibrous tissue to accommodate blood return to the heart

Vascular smooth muscle

• present in most blood vessels

• arranged in circular or spiral layers

• responsible for controlling vessel diameter

• muscle tone = maintain partial contraction at all times

Vasoconstriction

• decreases the diameter of the vessel lumen

Vasodilation

• increases it

Pericytes

• contractile cells surrounding capillaries

• forms mesh-like layer and regulates capillary permeability

• more pericytes ensures less leaky capillaries

Angiogenesis

• formation of new blood vessels

• regulated by balance of cytokine growth factors

  • angiogenic factors (vascular endothelial growth factor (VEGF)

  • fibroblast growth factor (FGF)

  • both promote vessel growth

• antiangiogenic factors

  • inhibit vessel growth

Flow (F)

• directly proportional to pressure difference and inversely to resistance (R)

• F = delta P / R

resistance to blood flow

• determined by radius of blood vessels, length of vessels, and viscosity of the blood

Blood pressure is highest in the arteries

• decreases continuously as blood moves through the circulatory system

• because resistance from vessel walls and friction between blood cells

• high pressure is maintained due to arterial elastic walls and energy storage during ventricular contraction

Pulse Pressure

• difference between systolic and diastolic pressure

• Pulse Pressure = Systolic Pressure - Diastolic Pressure

Mean Arterial Pressure (MAP)

= Diastolic Pressure + 1/3 (Pulse pressure

• MAP is proportional to the product of CO and arterial Resistance )

Hypotension

• low blood pressure

• insufficient driving force for blood flow

• reduced oxygen supply to the brain, dizziness, or fainting

Hypertension

• high blood pressure

• increased risk of blood vessel rupture

• 
  

Sphygmomanometer

• measures arterial blood pressure

• when cuff is inflated above systolic pressure, arterial blood flow stops

  • no sound heard because artery is completely compressed

• Cuff pressure is slowly released and falls between systolic and diastolic pressure

  • blood begins to flow through the compressed artery

  • creates turbulent flow and Korotkoff sounds per pulse

  • systolic pressure

• Cuff pressure drops below diastolic pressure, artery is no longer compressed, blood flow becomes smooth, and Korotkoff sounds disappear

• diastolic pressure

4 factors influencing MAP

• total blood volume

• cardiac output (effectiveness of the heart as a pump)

• resistance of the system to blood flow (arteriolar diameter)

• relative distribution of blood between arterial and venous vessels (venous diameter)

Peripheral Resistance (R)

• higher CO increases MAP if resistance remains constant

• primarily set by arteriolar diameter

• opposes blood flow out of the arteries

• increased resistance raises MAP if CO is unchanged

Arteries hold about 11% of total blood volume

• veins hold about 60%

• veins a reservoir that can shift blood to arteries as needed

Frank Starling Law

• venous constriction decreases venous volume and increases arterial volume and MAP

• enhances venous return and cardiac output

If arteries constrict…

• blood flow out of arteries decreases and MAP increases

• If CO decreases, arterial blood volume and MAP decrease

• If veins constrict, venous blood volume decrease, arterial volume and MAP increase

Increased blood volume raises MAP, while decreased blood volume lowers it

Poiseuille’s Law

• resistance to blood flow (R) is directly proportional to the length (L) of the vessel and viscosity (n) of the blood

• inversely proportional to the fourth power of the vessel radius: (r)^4

• vessel length and blood viscosity are usually constant, changes usually because of vessel radius

• arterioles = main site of variable resistance, contributing over 60% of total systemic resistance bc of smooth muscle (changes radius via contractions/relaxation)

Arterial resistance is regulated by:

• sympathetic reflexes

  • maintain mean arterial pressure and direct blood flow to tissues as needed

• Hormones

  • act on arterioles and influence kidney function, affecting blood pressure and volume

• Local control mechanisms

  • adjust blood flow to match metabolic needs of tissues (heart and skeletal muscle)

Key chemicals mediating vasoconstriction

• Norepinephrine (alpha receptors)

  • baroreceptor reflex, sympathetic neurons

• serotonin

  • platelet aggregation

  • smooth muscle contraction

• Endothelin

  • local control

• Vasopressin

  • increases blood pressure during hemorrhage

• Angiotensin II

  • increases blood pressure

Key chemicals mediating vasodilation

• epinephrine

  • increases blood flow to skeletal muscle, heart, and liver, from adrenal medulla

• Acetylcholine

  • erection reflection (via NO)

• Nitric Oxide

  • local control

• Bradykinin

  • increases blood flow

• Adenosine

  • matches blood flow to metabolism

• Decreased O2, Increased CO2, H+, K+

  • increase blood flow to match metabolism

• Histamine

  • increases blood flow

• Natriuretic peptides

  • reduce blood pressure

• Vasoactive intestinal peptide

  • digestive secretion and smooth muscle relaxation

Tonic release of norepinephrine from sympathetic neurons maintains arteriolar tone

• norepinephrine binds to alpha receptors on vascular smooth muscle, causing vasoconstriction

Most systemic arterioles are controlled by sympathetic neurons

• except those involved in erection reflection

  • vasodilation involved via parasympathetic mechanisms

Changes in sympathetic signal rate alter arteriole diameter

• increased norepinephrine release (higher signal rate) leads to vasoconstriction (decreased diameter)

Epinephrine from adrenal medulla also binds to alpha-receptors

• reinforces vasoconstriction, but alpha receptors have lower affinity for epinephrine than for norepinephrine

Epinephrine binds to B2-receptors on arterioles of the heart, liver, and skeletal muscle

• causes vasodilation

• these receptors are not innervated and respond mainly to circulating epinephrine

During fight or flight response

• increased sympathetic activity and epinephrine release cause vasoconstriction in nonessential organs

• vasodilation in heart, skeletal muscle, and liver

  • enhances blood flow to active tissues and divert away from less essential areas

Cardiovascular Control Center (CVCC) from CNS

• maintain adequate MAP to ensure sufficient blood flow to the brain and heart

• receives input from other brain regions, allowing it to selectively adjust blood flow to specific organs/tissues without affecting others

• integrating center

Baroreceptor Reflex

• main homeostatic control for MAP

• baroreceptors are stretch-sensitive mechanoreceptors located in carotid arteries and aorta

  • alter firing rate

  • increased BP → stretches baroreceptors + increased firing rate + CVCC increases parasympathetic output + decreased sympathetic output

    • less sympathetic output = less norepinephrine release = vasodilation, less peripheral resistance, decreased contraction → heart rate → cardiac output

    • more parasympathetic output = slows heart rate

  • decreased BP → reduces firing rate

• continuously monitors blood pressure to the brain and the body

• provides rapid adjustments to changes in blood pressure by altering cardiac output and/or peripheral resistance

relationship between mean arterial pressure, cardiac output, and peripheral resistance

• MAP proportional to CO x TPR

  • CO = cardiac output

  • TPR = total peripheral resistance

• 
  

Blood flow through the lungs equals total cardiac output

• all blood must pass through the lungs for oxygenation

Arterioles are arranged in parallel

• all receive blood simultaneously from the aorta

• total flow through all arterioles equals cardiac output

Constriction of an arteriole increases upstream arterial pressure (before constriction)

• decreases pressure downstream (after constriction)

• Total blood flow remains constant

  • even when individual arterioles constrict

  • distribution of flow shifts to vessels with lower resistance

Myogenic autoregulation

• allows arteriolar smooth muscle to regulate blood flow by adjusting resistance in response to changes in blood pressure

• blood pressure increases + stretches the arteriole wall, smooth muscle constricts → raises resistance and decreases blood flow to counteract initial pressure increase

• stretching of vascular smooth muscle opens mechanically gated channels, allowing cations to enter and depolarize the cell membrane

Depolarization opens voltage-gated Ca2+ channels

• influx

• incoming Ca2+ binds to calmodulin, activating myosin light chain kinase (MLCK)

  • increases myosin ATPase activity and crossbridge cycling, resulting in muscle contraction

Local Control of Blood Flow

• alter arteriole resistance

• regulates capillary blood supply to match tissue metabolic needs

• Arterioles constrict to decrease blood flow into capillary beds

  • dilate to increase blood flow into capillary beds

Paracrine Factors

• gases (O2, CO2, NO)

• released by endothelial or surrounding cells and mediate these changes in arteriole diameter

Active hyperemia

• when increased tissue metabolism leads to decreased O2 and increased CO2

• arterioles dilate, resistance decreases, blood flow increases to supply more O2

Reactive hyperemia

• after a temporary reduction in blood flow (occlusion)

• metabolic vasodilators (CO2, H+, NO) accumulate

• when flow resumes, arterioles dilate, causing a surge in blood flow until vasodilators are cleared and normal tone returns

Capillaries

• primary site for nutrient exchange of materials between blood and tissues

• density correlates with tissue and metabolic activity:

  • high metabolic rate = more capillaries per unit area

capillary walls

• extremely thin

• single layer of flattened endothelial cells on a basal lamina

• diameter only enough for RBCs to line up and pass

Continuous Capillaries

• leaky junctions between endothelial cells

• allows water and small solutes to pass

• found in muscle, connective, and neural tissue

• form blood brain barrier with tight junctions to protect neural tissue

Fenestrated Capillaries

• large pores (fenestrations) that permit rapid passage of high volumes of fluid

• kidney and intestine

• absorptive epithelia

Sinusoids

• modified, wider vessels in bone marrow, liver, spleen

• fenestrations and gaps between cells

• lack of basal lamina allow free exchange of proteins

• enable new blood cells to enter circulation

Transcytosis

• process in which vesicles transport proteins and macromolecules across the endothelium

• vesicles fuse to form temporary channels for exchange

Velocity of blood flow is inversely proportional to the total cross-sectional area of blood vessels

• as total cross-sectional area increases, velocity of blood decreases

• capillaries have largest total cross-sectional area, so have lowest velocity to accommodate for exchange between blood and interstitial fluid

Flow rate is determined by cardiac output, not by cross-sectional area

• cross-sectional area doesn’t affect flow rate

Exchange between plasma and interstitial fluid

1. movement between endothelial cells (paracellular pathway)

2. movement through the cells (endothelial transport)

• small dissolved solutes and gases move primarily by diffusion

  • lipid solubility dependent

  • diffusion rate is determined by concentration gradient

  • Oxygen and carbon dioxide diffuse freely across the endothelium

  • capillaries with leaky junctions allow most small solutes to diffuse freely

    • continuous capillaries restrict blood cells and most plasma proteins from passing through cell junctions

  • larger solutes and proteins are transported via vesicular transport (transcytosis)

  • vesicles can fuse to form open channels

Bulk Flow

• mass movement of fluid across capillary walls

  • caused by hydrostatic and osmotic pressure gradients

• Absorption

  • movement into capillaries

• Filtration

  • movement out of capillaries

Hydrostatic Pressure (Ph)

• pushes fluid out of capillaries

• starling force

Colloid osmotic pressure

• created by plasma proteins

• pulls fluid into capillaries

• starling force

• pressure much higher than in interstitial fluid, favoring water movement from interstitial fluid into plasma

Net Pressure

• Net pressure = Ph - pi

• If positive → net filtration

• If negative → net absorption

• usually capillaries transition from net filtration at arterial end to net absorption at venous end

Lymphatic System

• returns filtered fluid and proteins to the circulatory system

• transports absorbed fats from the small intestine

• filters pathogens for immune defense

Lymphatic Circulation

• starts with tiny, dead-end lymph capillaries near most blood capillaries

• capillaries have thin, overlapping endothelial cells

Lymph

• interstitial fluid, proteins, and particulates that enter capillaries by bulk flow

• lymph flow reliant on smooth muscle contractions, endothelial contractile fibers, one-way valves, and external compression from skeletal muscle activity

• immobilization = edema = fluid accumulation

Lymph vessels

• contain semilunar valves that ensure one-way flow, similar to veins

• lymph flows through progressively larger vessels, passing through lymph nodes that contain immune cells for pathogen filtration

• lymph is returned to the venous blood at the junction under the collarbones

Edema

• results from disrupted fluid exchange between circulatory and lymphatic systems

• Inadequate lymph drainage

  • lymphatic obstructions from parasites

  • cancer

  • fibrotic tissue growth

  • fluid accumulation in tissues

• Excessive capillary filtration relative to absorption

  • increased capillary hydrostatic pressure bc of elevated venous pressure → more fluid leaves capillaries → edema

• Decreased plasma concentration

  • reduces blood colloid osmotic pressure (pi), weakens force that draws fluid back into capillaries

• Increased interstitial proteins

  • from excessive protein leakage

  • lowers colloid osmotic pressure gradient

  • promotes net filtration out of capillaries