Blood vessels and blood pressure

I.  Introduction

- distribution of CO at rest

-  basic organization of the CV system

II.  Hemodynamics overview

A.  Blood flow, blood pressure, resistance

-blood flow:  volume of blood flowing through vessel/organ/ circulation per minute; as far as systemic circulation, blood flow = CO

-blood pressure: pressure gradient between 2 points in vasculature

-resistance:  opposition to flow due to friction

• Flow (F) = Pressure (P)/ Resistance (R)

B. Factors influencing resistance

- Pouiseuille-Hagen formula:  R = 8hL/pr⁴

• viscosity (h)-- friction of fluid molecules as they slide over one another

  • hematocrit

  • plasma protein concentration

  • constant for CV system

• length -- longer the vessel, greater surface area, greater resistance to flow

  • constant for CV system

• radius -- changing radius greatly alters surface area of vessel exposed to a given volume of blood

  • decreasing radius -- tremendously increases resistance

  • increasing radius -- tremendously decreases resistance

- by simplification, Pouiseuille-Hagen formula:  R = 1/r⁴

C.  Factors influencing blood flow in systemic circulation:  summary

• Flow (F) = Pressure (P)/ Resistance (R)

• CO = BP/R --> CO = BP x r⁴

III.  Arteries

A.  Functional anatomy

• intima -- single layer of endothelial cells

• media -- varying amounts of collagen, elastin, and smooth muscle

  • elastic arteries

  • muscular arteries

• adventitia -- fibrous connective tissue

B.  Low-resistance vessels -- blood rapidly moves from heart to tissues

C.  Pressure reservoirs -- provide driving force for blood during diastole, secondary pumps

- note that despite contraction-relaxation cycles, blood pressure through capillaries does not fluctuate -- not pulsatile

• during systole more blood enters arteries from heart than leaves them due to resistance of smaller vessels downstream

  • arteries expand temporarily, hold "excess" ejected blood

• during diastole heart does not pump blood into arteries, stretched arterial walls recoil, "excess" blood pushed to vessels downstream

• thus arteries play role in dampening pressure fluctuations occurring during cardiac cycle in ventricles

D.  Arterial pressure

- arterial pressure not constant as volume of blood entering arteries during systole is 1/3 greater to volume of blood leaving arteries during diastole

• systolic pressure:  highest pressure in arteries at peak of ejection (120 mm Hg)

  • only 1/3 of blood that enters arteries during this period leaves these vessels

• diastolic pressure:  lowest pressure in arteries during cardiac cycle (70 mm Hg)

  • lowest pressure achieved in arteries as blood is draining into remainder of vessels during diastole

• pulse pressure:  systolic pressure - diastolic pressure

• mean arterial pressure: (map) average pressure in artery throughout 1 turn of the cardiac cycle

  • (diastolic + 1/3PP)

III.  Arterioles

-  media proportionately the predominant layers, composed primarily of smooth muscle

- are the major resistance vessels of the vascular tree

• mean arterial pressure before arterioles is 93 mm Hg; pressure of blood leaving arterioles is 37 mm Hg

• arteriolar resistance also converts pulsatile systolic-diastolic pressure swings in arteries to non-pulsatile pressure seen in capillaries

• resistance changes achieved by varying radius of vessels

  • small change in radius, large change in resistance to blood flow and thus blood pressure

    • vasodilation

    • vasoconstriction

  • thus arterioles are prime controllers and regulators of blood pressure

-  arterioles display a state of partial constriction, vascular tone -- establishes a baseline resistance to blood flow

-  state of partial constriction due to:

• myogenic activity of arteriolar smooth muscle

  • SM membrane potential varies without hormonal or neural influences, results in self-regulated contractile activity

  • sympathetic fibers innervate media -- vasomotor fibers

    • tonically discharge

    • release norepinephrine -- in most beds maintains basal vascular tone

    • no parasympathetic innervation to arterioles

      • vasoconstriction -- increase sympathetic discharge

      • vasodilation -- decrease sympathetic discharge

• sympathetic fibers innervate media -- vasomotor fibers

  • tonically discharge

  • release norepinephrine -- in most beds maintains basal vascular tone

  • no parasympathetic innervation to arterioles

    • vasoconstriction -- increase sympathetic discharge

    • vasodilation -- decrease sympathetic discharge

A.  Local control of arteriolar radius

-  variably distributes cardiac output among various systemic beds so that blood flow matches tissues' metabolic needs

1. autoregulation:  capacity of tissues to regulate own blood flow
   • metabolic hypothesis
     • accumulation/absence of metabolites produces vasodilation/vasoconstriction of arterioles, respectively
       • pCO₂
       • pO₂
       • lactic acid 
       • adenosine
       • K⁺
       • temperature
   • myogenic hypothesis
     • vessel responds to increased stretch by reflex contraction
     • vessel responds to decreased blood flow by myogenic relaxation -- increases blood flow through area
   • example of reactive hyperemia -- response of blood vessel to occlusion
     • what happens when occlusion removed
     • what is role of myogenic and metabolic autoregulation processes in response?
2. control by substances secreted by endothelium (chemicals acting in paracrine fashion within vessel wall)
   • growth factors
     • role in vascular development/disease
     • PDGF, VEGF
   • vasoactive substances:  affect SMC tone
     • prostaglandin- vasodilation, inhibit platelet aggregation
     • thromboxane A2- vasoconstriction, platelet aggregation
     • EDRF (nitric oxide- NO)- increase intracellular Ca++ induces NO production in endothelial cells, produces relaxation of smooth muscle cells in adjacent media
     • endothelins- most potent vasoconstrictors known; produced by endothelial cells; stimuli varied -- increased shear stress, growth factors, hormones

B.  Systemic control of arteriolar radius

1. control by hormones- systemic regulation of arteriolar diameter
   • circulatory kinins - bradykinin
     • small polypeptides split away from a₂-globulins by enzymes in plasma or ISF
     • relax vascular SM through NO   
     • increase capillary permeability, attract leukocytes
   • norepinephrine/epinephrine
     • norepinephrine 
       • released by vasomotor fibers in arteriole media
         • high affinity for a receptors -- generalized vasoconstrictor effect
         • can bind b receptors -- vasodilatory effect
       • less abundant of adrenal medullary hormones
     • epinephrine
     • most abundant of medullary hormones
       • high affinity for b receptors -- vasodilatory effect
         • dilates vessels in skeletal muscle
   • atrial natriuretic factor (ANF)
     • decreases blood pressure by promoting fluid loss from plasma
   • vasopressin (ADH) -- elevates blood pressure
     • promotes water reabsorption in kidneys
     • vasoconstrictor
   • angiotensin II
     • part of renin-angiotensin-aldosterone cascade
     • important in maintenance of blood pressure during hemorrhage and shock
   • histamine
     • inflammatory response
2. Neural regulation of BP- systemic regulation of cardiovascular function

- Flow (F) = Pressure (P)/ Resistance (R)

- CO = BP/R --> CO = BP x r⁴

- since resistance is varied by altering arteriolar diameter, resistance is peripheral in circulation -- total peripheral resistance (TPR)

- CO = BP/TPR --> BP = CO x TPR

- thus can vary blood pressure by changing cardiac output and varying resistance of arterioles

• vasomotor tone maintains vascular tone of arterioles

  • maintains adequate driving pressure of blood to all systemic beds

    • if all arterioles dilate, blood pressure falls substantially, lose adequate driving force for blood flow

  • individual beds can use autoregulatory and local mechanisms to fine adjust amount of blood flow -- however need pressure head to drive flow

IV.  Capillaries

-  sites of exchanges (solutes and fluids) between blood and the tissues

-  exchanges between blood and the tissues are passive

• diffusion -- solutes

• bulk flow -- fluid

-  capillary structure permits such functions:

• diffusing molecules travel very short distances between blood and ISF and cells

• capillaries very narrow

• capillaries are very thin -- 1 mm diameter

  • single layer of flattened endothelial cells

• total surface area of capillaries is tremendous

  • influence on velocity of blood flow:  recall that velocity is displacement per unit time (cm/s) while flow is volume per unit time (cm³/s)

  • velocity (V) is proportional to flow (F) divided by area

  • V=F/A (cm/s = cm³/s/cm²)

• structure of capillary wall

  • exchanges possible across cell

    • diffusion

    • vesicular transport

  • exchanges possible between cell junctions

    • exact amount regulated by state of junction -- tight junction integrity and dynamics

  • exchanges possible via "pores" in cells, fenestrations

- a capillary bed and regulation of capillary perfusion:

• arteriole

• metarteriole -- thoroughfare channel

• true capillaries

  • precapillary sphincters -- open or close in response to metabolic status of tissue; work with arteriole autoregulation in control of perfusion through vascular bed

• post-capillary venule

- capillary exchanges -- diffusion of solutes across capillary wall

• exchanges occur between plasma and ISF (80% ECF)

  • composition of ISF reflects composition of plasma (20% ECF)

    • thus regulate composition of plasma to regulate composition of ISF (most ECF)

• exchanges of solutes by simple or facilitated diffusion

- capillary exchanges -- bulk flow

• movement of protein-free plasma out of capillary into ISF (filtration) at arterial end of capillary; movement of protein-free fluid from ISF into capillary (reabsorption) at venule end of capillary

• occurs because of differences between hydrostatic and osmotic pressures of plasma and ISF

  • outward pressures

    • capillary hydrostatic pressure

    • ISF osmotic pressure

  • inward pressures

    • plasma osmotic pressure

    • ISF hydrosatic pressure

• in most capillaries outward pressures prevail and arteriolar end and inward pressure greater at venule end

  • some capillaries reabsorption along full length

  • some capillaries filtration along full length

• note that on average more fluid filters out at arteriole end than at venule end

  • this fluid returned to circulation by lymphatics

  • other roles of lymphatics -- immune, GI absorption of fat

- clinical example of capillary dynamics -- edema

• reduced concentration of plasma proteins

  • renal failure

  • liver failure

  • protein deficient-diet

• increased permeability of capillary walls

• increased venous pressure

  • pregnancy -- edema in legs

• blockage of lymph vessels -- elephantiasis

V.  Veins

- veins are capacitance vessel -- on average 64% of blood in circulatory system at one time found in veins

- pressure gradient that drives flow through veins very small; veins have structural adaptation that allow them to perform their function -- return blood to heart -- despite this low gradient:

• very thin walls, little elastin

• little myogenic tone

• large radii -- offer very little resistance to flow

• have valves -- unidirectional flow of blood through veins

  • valve dysfunction

    • varicose veins

    • hemorhoids

-  factors that affect venous capacity will influence venous return and thus cardiac output (Starling's law):

• effect of vasomotor sympathetic tone on venous return

  • vasoconstriction decreases venous capacity and increases venous return

  • vasodilation increases venous capacity and decreases venous return

• effect of skeletal muscle activity on venous return

  • increased skeletal muscle activity milks veins -- increases venous return

• effect of respiratory pump

  • inspiration -- intra-thoracic pressure less than intra-abdominal -- suction of blood to heart

• cardiac suction

VI.  Regulation of blood pressure

1.  Short term regulatory mechanisms:  neural regulation of BP

- cardiovascular center (CV) in the medulla:

• Vasomotor center (VM): gives rise to sympathetic fibers that innervate smooth muscles of arterioles and veins; tonically discharges, arterioles always partially constricted, vasomotor tone; increased sympathetic activity will increase vasomotor tone (vasoconstriction); decreased sympathetic activity will decrease vasomotor tone (vasodilation)
• Cardioaccelerator center (CA): gives rise to sympathetic fibers that when activated increase HR and contractility of cardiac muscle
• Cardioinhibitory center (CI): gives rise to parasympathetic fibers that cause a decrease in HR.

1. innervation of blood vessels (sympathetic)

-adrenergic fibers

-cholinergic fibers

-originate in VM center (VC)

2.  innervation of heart (sympathetic)

-originate in VM center (CA)

3.  innervation of heart (PS)

-originate in CI center

-examine tonic discharge of each

• tonic discharge of VC- affects to veins and arterioles
• tonic discharge of CA vs CI- which one predominates

4.   Afferents to cardioregulatory center

a.   baroreceptors - via glossopharyngeal and vagus nerve to CV center; be familiar with neural pathway and examples of baroreceptor function.

-  baroreceptor resetting in hypertension

b.   chemoreceptors  -- role in blood pressure regulation