Functions of Peripheral Circulation

1. Contain the blood

2. Exchange nutrients, waste products, and gases with tissues

3. Transport

4. Regulate blood pressure, along with cardiac output

5. Control direction of blood flow

6. Participate in thermoregulation

Peripheral Circulation and Regulation

Blood Vessel Structure and Function

Blood vessels – ‘closed system’

• delivery system of dynamic structures that begins and ends at heart

• Work with lymphatic system to circulate fluids

Arteries - delivery

• carry blood away from ventricles

• oxygenated except for pulmonary circulation and umbilical arteries of fetus

• closer to the heart, greater the pressure artery must tolerate

Capillaries - exchange

• Numerous small vessels = high surface area

• direct contact with tissue cells; directly serve cellular needs

• ‘endothelium’ only one layer of squamous cells

Veins - return

• carry blood toward atria

• deoxygenated except for pulmonary circulation and umbilical veins of fetus

• Built to tolerate lower blood pressures and prevent backflow

60,000 miles of vessels in average body

Venous system

Large veins(capacitancevessels)

Largelymphaticvessels

Arterial system

Arteriovenousanastomosis

Lymphaticsystem

Lymphaticcapillaries

Postcapillaryvenule

Sinusoid

Metarteriole

Terminalarteriole

Arterioles(resistancevessels)

Musculararteries(distributingarteries)

Elasticarteries(conductingarteries)

Heart

Small veins(capacitancevessels)

Lymphnode

Capillaries(exchangevessels)

Precapillarysphincter

Thoroughfarechannel

Note subdivisions and by-pass vessels

Arteries run deep, whereas veins are both deep and superficial

Venous pathways are more interconnected

Smooth Muscle – see last portion of Ch. 9

• Found in walls of most hollow organs:• Unitary SM: digestive, urinary, reproductive

• Gap junctions unify the muscle sheets into functional syncytium

• Multi-unit SM: Respiratory, circulatory (except in smallest of blood vessels), skin • Gap junctions generally absent, individual units must be stimulated directly

• Not found in heart – heart contains cardiac muscle, not smooth

• Most smooth muscle organized into sheets of tightly packed fibers

• Many organs contain two layers of sheets with fibers oriented at right angles to each other – but not in blood vessels• Longitudinal layer: fibers run parallel to long axis of organ

• Contraction causes organ to shorten

• Circular layer: fibers run around circumference of organ• Contraction causes lumen of organ to constrict

Differences Between Smooth and Skeletal MuscleCharacteristic Skeletal Muscle Smooth Muscle

Fiber Characteristics 1. Long, thin, multinucleate fibers2. Myofibrils highly organized into sarcomeres 3. Troponin/Ca+2 binding moves tropomyosin4. Sliding actin pulls on Z disks5. Sarcomeres arranged parallel to the length of the fiber shortening fiber during contraction

1. Small, spindle-shaped, fibers each with a central nucleus2. No sarcomeres, actin and myosin present but myosin is short with heads along entire length3. No troponin – calmodulin instead causes P addition to myosin4. Sliding actin pulls on intermediate filaments and dense bodies anchored to the sarcolemma5. Actin/myosin arranged diagonally causing cell to ‘corkscrew’ when contracted

Connective Tissue Involvement

Connective tissue throughout including organized layers: endo-, peri- and epimysium

Some endomysium present

Linkage to the Nervous System

Neuromuscular junction contains chemical synapse between motor neuron and individual fiber

Autonomic neurons terminate forming diffuse junctions between neuron varicosities and areas containing multiple fibers

Excitation-ContractionCoupling

1. Triads consisting of one T-tubule flanked by SR terminal cisterns located at the each of each A Band. 2. Ca+2 stored in SR stimulates cross bridge formation

1. No T-tubules or terminal cisterns, no pattern to SR. Extracellular Ca+2 primary stimulus for contraction. 2. Caveolae in sarcolemma contain gated Ca+2 channels

Fiber to Fiber Communication

1. NONE2. Contraction of one fiber does not cause contraction of another

1. Gap junctions between fibers spread depolarization cell to cell2. Synchronized contraction like cardiac muscle

Innervation of Smooth Muscle

Sources of Ca2+ for Smooth Muscle Contraction

Intermediate Filaments and Dense Bodies of Smooth Muscle Fibers Harness the Pull Generated by Myosin Cross Bridges

Smooth Muscle Contraction

• Slow, synchronized – slow to contract, slow to relax• Can stay contracted for long periods without fatigue

• Pacemaker cells present in some organs• Waves of contraction occur regularly in organs like intestines

• Exhibits tone in many organs

• Neurotransmitters and hormones may stimulate contraction or relaxation• ACh stimulates bronchial SM to contract; Norepinephrine inhibits causing

relaxation

• Highly dependent on location: NE in blood vessel SM causes contraction

• Stretch-relaxation response• In most cases, forces that stretch SM cause relaxation of fibers

• Length vs tension response more tolerant of stretch

Photomicrograph of Artery and Vein

lumen

Or externa

Structure of Blood Vessel WallTunica intima

• Smooth, friction-reducing, innermost layer in contact with blood

• Endothelium: simple squamous epithelium lines lumen of all vessels is continuous with endocardium

Tunica media

• Middle layer composed mostly of smooth muscle and sheets of elastin

• Sympathetic vasomotor nerve fibers innervate this layer

• Thickest in arteries - responsible for maintaining blood flow and blood pressure

Tunica externa

• Outermost layer of wall

• mostly loose collagen fibers that protect and reinforce wall and anchor it to surrounding structures

• Infiltrated with nerve fibers, lymphatic vessels, and Vasa vasorum

Capillaries

• Endothelium with sparse basal lamina

Tunica media(smooth muscle and elastic fibers)

• External elastic membrane

Tunica externa(collagen fibers)

• Vasa vasorum

Artery Vein

LumenLumen

Valve

Endothelial cells

Basement membrane

Capillarynetwork

Capillary

Tunica intima

• Endothelium

• Internal elastic membrane

• Subendothelial layer

Vasomotor tone: what’s up with that?

conducting arteries-maintain pressure between contractions

distributing arteries -deliver to organs

resistance arteries-control perfusion locally

capacitance vessels - Serve as blood reservoir

Red bloodcell in lumen

Intercellularcleft

Endothelialcell

Endothelial nucleus

Tight junction Pinocytoticvesicles

Pericyte

Basementmembrane

Continuous capillaries are the least permeable and most common.

Continuous Capillaries:• Abundant in skin, muscles, lungs, and CNS.• Often have associated pericytes.• Pinocytotic vesicles ferry fluid across the endothelial cell.• Brain capillary endothelial cells lack intercellular clefts and have tight junctions around

their entire perimeter.

Continuous capillary

Capillaries

• Functions: exchange between blood and interstitial fluid

• Small diameter vessels force RBCs to pass in single file• Slows flow and promotes exchange

• Thin tunica intima; in smallest vessels, one cell forms entire circumference

• Supply almost every cell, except for cartilage, epithelia, cornea, and lens of eye

Red bloodcell in lumen

Intercellularcleft

Fenestrations(pores)

Endothelialcell

Endothelialnucleus

Basement membrane Tight junction

Pinocytoticvesicles

Fenestrated capillary

Fenestrated capillaries have large fenestrations (pores)

that increase permeability.

Fenestrated Capillary:

Occur in areas of active filtration (e.g., kidney) or absorption (e.g., small intestine), and areas of endocrine hormone secretion.

• Fenestrations are Swiss cheese–like holes that tunnel through endothelial cells.• usually covered by a very thin diaphragm• Readily allows solute and fluid movement.

• In some digestive tract organs, the number of fenestrations in capillaries increases during active absorption of nutrients.

Nucleus ofendothelialcell

Red bloodcell in lumen

Endothelialcell

Tight junction

Largeintercellularcleft

Incompletebasement membrane

Sinusoid capillary

Sinusoid capillaries are the most permeable and

occur in limited locations.

• Allow large molecules and even cells to pass across their walls.• Blood flows slowly through their channels.• Macrophages may extend processes through the clefts to catch “prey” or, in liver, form part of the

sinusoid wall.

Sinusoidal Capillaries:

• Occur in liver, bone marrow, spleen, and adrenal medulla.• Have large intercellular clefts as well as fenestrations; few tight junctions; incomplete basement

membranes.• Are irregularly shaped and have larger lumens than other capillaries.

Anatomy of a capillary bed.

Sphincters open—blood flows through true capillaries.

Precapillary

sphincters Metarteriole

Vascular shunt

Terminal arteriole Postcapillary venule

Terminal arteriole Postcapillary venule

Thoroughfare

channel

True

capillaries

Sphincters closed—blood flows through metarteriole –

thoroughfare channel and bypasses true capillaries.

• Capillary bed: interwoven network of capillaries between arterioles and venules

• Microcirculation: flow of blood through bed

Capillary beds vessels

1. Vascular shunt: channel that connects arteriole directly with venule (metarteriole–thoroughfare channel)

2. True capillaries: actual vessels involved in exchange

50

40

30

20

10

0

5000

Relative cross-sectional area ofdifferent vesselsof the vascular bed

4000

3000

2000

1000

0

Total area(cm2) of thevascularbed

Velocity ofblood flow(cm/s)

Venules• postcapillary venules consist of endothelium and a few pericytes

– Very porous; allow fluids and WBCs into tissues

• Larger venules have one or two layers of smooth muscle cells

Veins•Have all tunics

• Large lumen and thin walls make veins good storage vessels

•Blood pressure lower than in arteries, so adaptations ensure return of blood to heart

Relative proportion of blood volume throughout the cardiovascular system.

Pulmonary blood

vessels 12%

Heart 8%

Capillaries 5%

Systemic arteries

and arterioles 15%

Systemic veins

and venules 60%

Venous reservoir provides a source of blood to fill dilating arteries upon initiation of exercise – compensation to maintain blood pressure

Cap

illar

y tr

ansp

ort

mec

han

ism

s

Basementmembrane

Endothelialfenestration(pore)

Intercellularcleft

Pinocytoticvesicles

Caveolae

Transportvia vesiclesor caveolae(largesubstances)

Movementthroughfenestrations(water-solublesubstances)

Movementthroughintercellular clefts(water-solublesubstances)

Diffusionthroughmembrane(lipid-solublesubstances)

Lumen

3

21

4

Fluid Movements Out of Capillaries

Capillary pressures •35 mm Hg at beginning of capillary bed •∼17 mm Hg at the end of the bed•Low capillary pressure is desirable

• Fluid is forced out clefts of capillaries at arterial end, and most returns to blood at venous end

• Bulk fluid flow across capillary walls causes continuous mixing of fluid between plasma and interstitial fluid; maintains interstitial environment.

•Direction and amount of fluid flow depend on two opposing forces • Hydrostatic pressures• Colloid osmotic pressures

Hydrostatic pressure (HP)

• Capillary hydrostatic pressure (HPc)

• Interstitial fluid hydrostatic pressure (HPif): assumed to be zero because lymphatic vessels drain interstitial fluid

Capillary colloid osmotic pressure (oncotic pressure, OPc)

• Remember the presence of plasma proteins

Interstitial fluid colloid osmotic pressure (OPif)

• inconsequential

Hydrostatic-osmotic pressure interactions

• Net filtration pressure (NFP): • NFP = (HPc + OPif) − (HPif + OPc)

• Net fluid flow out at arterial end (filtration)

• Net fluid flow in at venous end (reabsorption)

• More fluid leaves at arterial end than is returned at venous end• Excess interstitial fluid is returned to blood via lymphatic system

HPif = 0 mm Hg

NFP = 10 mm Hg

HPc = 35 mm Hg

OPif = 1 mm Hg

OPc = 26 mm Hg

Osmotic pressure (OPif) in interstitial fluid “pulls”fluid out of capillary.

Hydrostatic pressure(HPif) in interstitial fluid“pushes” fluid intocapillary.

Hydrostatic pressure in capillary(HPc) “pushes” fluid out of capillary.

Osmotic pressure in capillary(OPc) “pulls” fluid into capillary.

Boundary

(capillary wall)

Interstitial fluidCapillary lumen

How do the pressures drive fluid flow across a capillary?

Net filtration occurs at the arteriolar end of a capillary.

Let’s use what we know about pressures

to determine the net filtration pressure

(NFP) at any point. (NFP is the pressure

driving fluid out of the capillary.) To do

this we calculate the outward pressures

(HPc and OPif) minus the inward

pressures (HPif and OPc). So,

As a result, fluid moves from thecapillary into the interstitial space.

NFP = (HPc + OPif) − (HPif + OPc)

= (35 + 1) − (0 + 26)

= 10 mm Hg (net outward pressure)

NFP= −8 mm Hg

HPif = 0 mm Hg

HPc = 17 mm Hg

OPc = 26 mm Hg

OPif = 1 mm Hg

Net reabsorption occurs at the venous end of a capillary.

Hydrostatic pressure in capillary“pushes” fluid out of capillary.The pressure has droppedbecause of resistanceencountered along the capillaries.

Osmotic pressure in capillary“pulls” fluid into capillary.

Boundary(capillary wall)

Interstitial fluid

Hydrostatic pressure ininterstitial fluid “pushes”fluid into capillary.

Osmotic pressure ininterstitial fluid “pulls” fluid out of capillary.

Again, we calculate the NFP:

NFP = (HPc + OPif) − (HPif + OPc)

= (17 + 1) − (0 + 26)

= −8 mm Hg (net inward pressure)

Notice that the NFP at the venous endis a negative number. This means thatreabsorption, not filtration, is occurringand so fluid moves from theinterstitial space into the capillary.

Capillary lumen

Arterial side NFP = 10; venous side NFP = -8Capillary bed NFP is therefore 10 – 8 = 2 mm Hg2 mm Hg pressure causes a net fluid loss from bed to tissues

Venule

Arteriole

Lymphatic

capillary

The big picture

Each day, 20 L of fluid filters from

capillaries at their arteriolar end and

flows through the interstitial space.

Most (17 L) is reabsorbed at the

venous end.

17 L of fluid per

day is reabsorbed

into the capillaries

at the venous end.

Fluid moves

through the

interstitial space.

For all capillary beds, 20 L

of fluid is filtered out per

day—almost 7 times the

total plasma volume!

About 3 L per

day of fluid

(and any leaked

proteins) are

removed by the

lymphatic

system

Control Over Blood Pressure and FlowBlood pressure (BP)

• Expressed in mm Hg, systolic over diastolic

• Measured as systemic arterial BP in large arteries at same level as heart

• Pressure gradient provides driving force that keeps blood moving from higher- to lower-pressure areas

Blood flow

• Measured in ml/min

• Overall is relatively constant when at rest, varies at individual organ level, based on needs

Resistance (peripheral resistance)

• Measurement of amount of friction blood encounters with vessel walls, generally in peripheral (systemic) circulation

• Three important sources of resistance• Blood viscosity• Total blood vessel length• Blood vessel diameter

Laminar flow – frictional forces slow blood in direct contact with endothelium

Turbulent flow – constrictions in vessel interrupt laminar flow, eddys result

• Blood viscosity• The thickness or “stickiness” of blood due to formed elements and plasma

proteins

• Increased viscosity equals increased resistance

• Increasing hematocrit increases viscosity

• Total blood vessel length• The longer the vessel, the greater the resistance encountered

• Essentially remains constant once adulthood is reached

• Goal of blood pressure regulation is to keep blood pressure high enough to provide adequate tissue perfusion, but not so high that blood vessels are damaged• Example: If BP to brain is too low, perfusion is inadequate, and person loses

consciousness

• If BP to brain is too high, person could have stroke

Systolic pressure

Mean pressure

Diastolicpressure

0

20

40

60

80

100

120

Blo

od

pre

ssure

(m

m H

g)

• Pumping action of heart generates blood flow

• Pressure results when flow is opposed by resistance

• Systemic pressure is highest in aorta and declines throughout pathway• Steepest drop occurs in

arterioles

Pulse Pressure = 120-80 mmHg or 40 mmHg

Arterial Blood Pressure

•Pulse pressure and mean arterial pressure (MAP) both decline with increasing distance from heart•With increasing distance, flow is nonpulsatile

with a steady MAP pressure

Measuring Arterial Blood Pressure using auscultatory methods and a sphygmomanometer

1. Wrap cuff around arm superior to elbow2. Increase pressure in cuff until it exceeds systolic pressure

in brachial artery3. Pressure is released slowly, and examiner listens for

sounds of Korotkoff with a stethoscope

Venous Blood Pressure

•Small pressure gradient, only about 15 mm Hg

•Factors aiding venous return1. Backflow prevention - Venous valves 2. Muscular pump3. Respiratory pump4. Sympathetic venoconstriction5. Large-diameter lumens offer little resistance 6. Hydraulic ‘filling’ effect7. Larger number of vessels compared to arteries8. Anastomosis common

The muscular pump.

Venous valve(open)

Contractedskeletalmuscle

Vein

Venous valve(closed)

Direction ofblood flow

Regulation of Blood Pressure

•Maintaining blood pressure requires cooperation of heart, blood vessels, and kidneys• All supervised by brain

•Three main factors regulating blood pressure• Cardiac output (CO)• Peripheral resistance (PR or just R)• Blood volume

•Blood pressure varies directly with CO, PR, and blood volume

Poiseuille’s LawSimplifying: Flow = π (P) r4

----------------8 v l

1. Resistance to flow is caused by viscosity, vessel length, and vessel radius1. Once mature, length of vessel fairly constant – no impact 2. Viscosity and flow are inversely proportional – Homeostatic mechanisms

control viscosity3. Small changes in radius or diameter (vasoconstriction/dilation)

significantly impact flow

2. Minimum pressure differential required - no difference, no flowa) Must maintain pressure above critical closing pressureb) Heart as the generator of pressure can compensate

•P = P1 – P2 or the change in pressure over the length of the vessel

• v is the viscosity of the blood• l is the length of the blood vessel from P1 to P2

• r is the radius of the blood vessel (diameter = 2r)• π is a constant

Regulation of Blood Pressure

MAP = SV HR R

•Anything that increases SV, HR, or R will also increase MAP• SV is affected by venous return (EDV)• HR is maintained by medullary centers • R is affected mostly by vessel diameter

Regulation of Blood Pressure

•Factors can be affected by:•Short-term regulation: neural controls

• Neural controls operate via reflex arcs that involve:• Cardiovascular center of medulla

• Baroreceptors

• Chemoreceptors

• Higher brain centers

•Short-term regulation: hormonal controls•Long-term regulation: renal controls

Baroreceptor reflex

Baroreceptors

in carotid sinusesand aortic arch

are stimulated.

Rate of

vasomotor impulsesallows vasodilation,

causing R.CO and R

return bloodpressure to

homeostatic range.

Sympathetic

impulses to heartcause HR,

contractility, and

CO.

Impulses from baroreceptors

stimulate cardioinhibitory center(and inhibit cardioacceleratory

center) and inhibit vasomotor center.

Stimulus:

Blood pressure(arterial blood

pressure rises

above normalrange).

CO and R

return blood pressure to

homeostatic

range.

Vasomotor

fibers stimulatevasoconstriction,

causing R.

Stimulus:

Blood pressure(arterial blood

pressure falls below

normal range).

Baroreceptors

in carotid sinusesand aortic arch

are inhibitedSympathetic

impulses to heartCause HR,

contractility, and

CO.

Impulses from baroreceptors

activate cardioacceleratory center(and inhibit cardioinhibitory center)

and stimulate vasomotor center.

Homeostasis: Blood pressure in normal range

2

3

4b

5

4a

1

54b

1

2

3

4a

Short-Term Regulation: Neural Controls (cont.)

• Chemoreceptor reflexes• Aortic arch and large arteries of neck detect increase in CO2, or drop

in pH or O2

• Cause increased blood pressure by:• Signaling cardioacceleratory center to increase CO

• Signaling vasomotor center to increase vasoconstriction

• Influence of higher brain centers• Reflexes that regulate BP are found in medulla

• Hypothalamus and cerebral cortex can modify arterial pressure via relays to medulla• increases blood pressure during stress

• mediates redistribution of blood flow during exercise and changes in body temperature

Short-Term Mechanisms: Hormonal Controls

• Hormones regulate BP in short term via changes in peripheral resistance or long term via changes in blood volume

• Adrenal medulla hormones• Epinephrine and norepinephrine from adrenal gland increase CO and

vasoconstriction

• Angiotensin II stimulates vasoconstriction

• ADH (or vasopressin): high levels can cause vasoconstriction

• Atrial natriuretic peptide decreases BP by antagonizing aldosterone, causing decreased blood volume

An error here

Arterial pressure

Blood volume

Aldosterone

Mean arterial pressure

Blood volume

Mean arterial pressure

Filtration by kidneys

Urine formation

Arterial pressure

Inhibits baroreceptors

Sympathetic nervoussystem activity

Water intakeWater reabsorption

by kidneys

Sodium reabsorption

by kidneys

ADH release by

posterior pituitary

Vasoconstriction;

peripheral resistanceThirst via

hypothalamusAdrenal cortex

Angiotensin II

Angiotensin converting

enzyme (ACE)

Secretes

Initial stimulus

Physiological response

Result

Direct renal mechanism

Angiotensin I

Angiotensinogen

Renin releasefrom kidneys

Indirect renal mechanism (renin-angiotensin-aldosterone)

Summary of Factors that Increase MAPActivity ofmuscularpump andrespiratory

pump

Fluid loss fromhemorrhage,

excessivesweating

Crisis stressors:exercise, trauma,

bodytemperature

Baroreceptors

Release of ANPP

Vasomotor tone;bloodbornechemicals

(epinephrine,NE, ADH,

angiotensin II)

Dehydration,high hematocrit

Body size

Conservationof Na+ and

water by kidneys

Blood volumeBlood pressure

Blood pHO2

CO2

ChemoreceptorsBloodvolume

Venousreturn

Activation of vasomotor and cardio-acceleratory centers in brain stem

Strokevolume

Heartrate

Diameter ofblood vessels

Bloodviscosity

Blood vessellength

Peripheral resistanceCardiac output

Mean arterial pressure (MAP)

Initial stimulus

Physiological response

Result

Control of Blood FlowTissue perfusion: blood flow through body tissues; involved in:

1. Delivery of O2 and nutrients to, and removal of wastes from, tissue cells

2. Gas exchange (lungs)

3. Absorption of nutrients (digestive tract)

4. Urine formation (kidneys)

• Rate of blood flow is controlled by extrinsic and intrinsic factors• Extrinsic control: sympathetic nervous system and hormones control blood flow

through whole body

• Intrinsic control: Autoregulation (local) control of blood flow: blood flow is adjusted locally to meet specific tissue’s requirements• Local arterioles that feed capillaries can undergo modification of their diameters• Organs regulate own blood flow by varying resistance of own arterioles• Metabolic controls – smooth muscle response to metabolic wastes• Myogenic controls – smooth muscle response to increasing and decreasing MAP• Long-term autoregulation – angiogenesis and vessel enlargement

Intrinsic and extrinsic control of arteriolar smooth muscle in the systemic circulation

Intrinsic controls

(autoregulation)

• Metabolic or myogenic controls

• Distribute blood flow to individual

organs and tissues as needed

Vasoconstrictors

Myogenic

• Stretch

Metabolic

• Endothelins

Sympathetic tone

Neural

Hormonal

• Angiotensin II

• Antidiuretic hormone

• Epinephrine

• Norepinephrine

Extrinsic controls

• Neural or hormonal controls

• Maintain mean arterial pressure

(MAP)

• Redistribute blood during exercise

and thermoregulation

Metabolic

• Prostaglandins

• Adenosine

• Nitric oxide

O2

CO2

H+

K+

Neural

Hormonal

• Atrial natriuretic

peptide

Sympathetic tone

Vasodilators

Brain

Heart

Skeletalmuscles

Skin

Kidneys

Abdomen

Other

750

250

1200

500

1100

1400

600

750

750

12,500

600

600

400

1900

Total blood flow duringstrenuous exercise17,500 ml/min

Total bloodflow at rest5800 ml/min