Cardiovascular Physiology（心血管生理学）

Qiang XIA ( 夏强 ), MD & PhDDepartment of Physiology

Room C518, Block C, Research Building, School of MedicineTel: 88208252

Email: xiaqiang@zju.edu.cn

Vascular Physiology （血管生理学）

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Lecture Outline

• Functional parts of blood vessels• Hemodynamics• Arterial blood pressure• Microcirculation• Venous pressure and venous return• The lymphatic system

Functional parts of blood vessels

Elastic vessels (Windkessel vessels)

（弹性血管）

Resistance vessels (Precapillary

resistance vessels) （阻力血管） Exchange vessels （交换血管）

Capacitance vessels （容量血管）

Distribution vessels （分布血管）

Shunt vessels （短路血管）

Hemodynamics （血流动力学）

• Blood flow

Q= P/R = (P1-P2)/R

Q= PA/RQ: cardiac output, 5 L/minR: total peripheral resistancePA: aortic pressure

Poiseuille Law: Q=Pr4/8L: viscosity

r: radius of the vessel

L: length of the vessel

Q= P/R

Resistance of blood flow

R= 8L/r4

Jean Louis Marie Poiseuille \pwä-'zəi\ (April 22, 1799 - December 26, 1869) was a French physician and physiologist.Poiseuille was born in Paris, France.From 1815 to 1816 he studied at the École Polytechnique in Paris. He was trained in physics and mathematics. In 1828 he earned his D.Sc. degree with a dissertation entitled Recherches sur la force du coeur aortique. He was interested in the flow of human blood in narrow tubes.

r: main determinant of blood flow

If the radius of an arteriole is halved, its resistance will fall to ___ of its original value.

A 1/2

B 1/4

C 1/8

D 1/16

E 1/32

Decreasing the radius of a vessel by one-half its original radius will have what effect upon blood flow to distal portion?

A Blood flow will decrease to 50% of original flow.

B Blood flow will decrease by 25% of original flow.

C Blood flow will decrease to 10% of original flow.

D Blood flow will decrease to 6% of original flow.

Arteries

Arterial blood pressure （动脉血压）

Blood pressure measurement1. Direct (invasive) measurement technique

2. Indirect (non-invasive) measurement technique

Systolic pressure (SP ，收缩压 ): the maximum arterial pressure reached during peak ventricular ejection

Diastolic pressure (DP ，舒张压 ): the minimum arterial pressure just before ventricular ejection begins

Pulse pressure (PP ，脉压 ): the difference between SP and DP

Mean arterial pressure (MAP ，平均动脉压 ): the average pressure in the cardiac cycle (=DP+1/3PP)

Mean arterial pressure (MAP)

To estimate systolic and diastolic pressures, pressure isreleased from an inflatable cuff on the upper arm whilelistening as blood flow returns to the lower arm.

Blood Pressure Classification Chart

Category Systolic (mm Hg) Diastolic (mm Hg)

Normal Lower than 120 Lower than 80

Prehypertension 120 - 139 80 - 89

Hypertension

Stage 1 140-159 90-99

Stage 2 160 or higher 100 or higher

Adapted from The Seventh Report on the joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), NIH Publication No. 03-5233, May 2003

The classification chart is based on adults, aged 18 and older, who are not taking high blood pressure medicines and who are not acutely ill. If systolic and diastolic measurements fall into different categories, the higher category should be used to classify the person's blood pressure status.

Classification of blood pressure for adults age 18 years and older

Factors affecting arterial blood pressure

• Stroke volume• Heart rate

• Peripheral resistance• Elastic vessels• Blood volume

Ventricular ejection

Q= PA/R

Q: cardiac output (CO)

R: total peripheral resistance (SVR)

PA: aortic pressure (MAP)

MAP = CO SVR

1 2

3

5

4

The blood moved in asingle heart contraction stretches out the arteries, so that their recoil continues to push on the blood, keeping it moving during diastole.

Movement of blood into and out of the arteries during the cardiac cycle

Arterial pulse （动脉脉搏）

In response to the pulsatile contraction of the heart:

pulses of pressure move throughout the vasculature, decreasing in amplitude with distance

Arterial pulse

recorded in different

vessels

Arterial pulse

recorded under

different conditions

Clinical Application of Arterial Pulse

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Systematic examination of pulses:

Which and what order? Where and how? Why?1. Radial artery •Radial side of wrist.

•With tips of index and middle fingers.•To assess rate and rhythm.•Simultaneously with femoral to detect delay.•Not good for pulse character.

2. Brachial artery •Medial border of humerus at elbow medial to biceps tendon.•Either with thumb of examiner's right hand or index and middle of left hand.

•To assess pulse character.•To confirm rhythm.

3. Carotid artery •Press examiner's left thumb against patient's larynx.•Press back to feel carotid artery against precervical muscles.•Alternatively from behind, curling fingers around side of neck.

•Best for pulse character and, to some extent, left ventricular function.•To detect carotid stenosis.•At resuscitation (CPR).

4. Femoral artery •Patient lying flat and undressed.•Place finger directly above pubic ramus and midway between pubic tubercle and anterior superior iliac spine.

•To assess cardiac output.•To detect radiofemoral delay.•To assessperipheral vascular disease.

5. Popliteal artery •Deep within the popliteal fossa.•Compress against posterior of distal femur with knee slightly flexed.

•Mainly to assess peripheral vascular disease.•In diabetics.

6. Dorsalis pedis (DP) and tibialis posterior (TP) arteries (foot)

•Lateral to extensor hallucis longus (DP).•Posterior to medial malleolus (TP).

•As above.

7. The abdominal aorta •With the flat of the hand per abdomen, as body habitus allows.

•In peripheral vascular disease.•To detect aneurysmal swelling.

From: http://www.patient.co.uk/

Microcirculation （微循环）

Function:Transfer of substances between blood & the tissues

Structure of microcirculation

A-V shunt

• Circuitous channel (Nutritional channel) （营养通路）

3 pathways

A-V shunt

12

3

4

5

• Thoroughfare channel （直捷通路）

A-V shunt

12

3

4

5

• Arteriovenous shunt (A-V shunt) （动 - 静脉短路）

A-V shunt

12

3

4

5

• Blood travels from artery to arteriole to capillary to venule to vein

Arterioles （微动脉）Two major roles:

• To be responsible for determining the

relative blood flow in individual organs at

any given MAP• To be a major factor in determining MAP

Arterioles

• Small precapillary resistance vessels (10-50 μ) composed of an endothelium surrounded by one or more layers of smooth muscle cells

• Richly innervated by sympathetic adrenergic fibers and highly responsive to sympathetic vasoconstriction via both α1 and α2 postjunctional receptors

• Represent a major site for regulating systemic vascular resistance• Rhythmical contraction and relaxation of arterioles sometimes

occurs (i.e., spontaneous vasomotion)• Primary function within an organ is flow regulation, thereby

determining oxygen delivery and the washout of metabolic by-products

• Regulate, in part, capillary hydrostatic pressure and therefore influence capillary fluid exchange

Dynamic adjustments in the blood distribution to the organs is accomplished by relaxation and contraction of circular smooth muscle in the arterioles.

Local Control of Blood Flow

• The mechanism independent of nerves or hormones by which organs and tissues alter their own arteriolar resistances, thereby self-regulating their blood flows– Active hyperemia （主动充血）– Flow autoregulation （血流自身调节）– Reactive hyperemia （反应性充血）– Local response to injury （对损伤的局部反应）

Active hyperemia and flow autoregulation differ in their cause but both result in the production of the same local signals that provoke vasodilation.

Local control of organ blood flow

• Reactive hyperemia – When an organ or tissue has had its blood supply completely occluded, a profound transient increase in its blood flow occurs as soon as the occlusion is released

• Response to injury – Tissue injury causes a variety of substances to be released locally from cells or generated from plasma precursors. These substances make arteriolar smooth muscle relax and cause vasodilation in an injured area

Extrinsic Control

• Sympathetic nerves （交感神经）• Parasympathetic nerves （副交感神经）• Noncholinergic, nonradrenergic autonomic

neurons (NO or other noncholinergic vasodilator substances) （ NANC ）

• Hormones (epinephrine, angiotensin II, vasopressin, atrial natriuretic peptide)

Sympathetic stimulation of alpha-adrenergic receptors cause vasoconstriction to decrease blood flow to that location.

Sympathetic stimulation of beta-adrenergic receptors lead to vasodilation to cause an increase in blood flow to that location.

Renin-angiotensin system （肾素 - 血管紧张素系统）

ANGII can be produced directly by conversion of angiotensinogen by the tissue plasminogen activator (tPA), cathepsin G and tonin or by hydrolysis of angiotensin I by chymase and cathepsin G.

CAGE = chymostatin-sensitive angiotensinII-generating enzyme

Robert Toto & Biff F. Palmer. Am J Nephrol 2008;28:372–380

Vasopressin （血管升压素）

•Vasodilator factors

•PGI2 – prostacyclin （前列环素）

•EDRF (endothelium-derived relaxing factor, nitric oxide)

•EDHF (endothelium-dependent hyperpolarizing factor)

Endothelium-derived vasoactive substances

The 1998 Nobel Prize in Physiology or Medicine

Nitric oxide as a signaling molecule in the cardiovascular system

Louis J Ignarro Ferid Murad Robert F Furchgott

Sildenafil, the prototypical PDE5 inhibitor

A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. These drugs are used in the treatment of erectile dysfunction, and were the first effective oral treatment available for the condition. Because PDE5 is also present in the arterial wall smooth muscle within the lungs, PDE5 inhibitors have also been explored for the treatment of pulmonary hypertension, a disease in which blood vessels in the lungs become abnormally narrow.

•Vasoconstrictor factors – Endothelin-1 （内皮素 -1 ）

Diversity among signals that influence contraction/relaxationin vascular circular smooth muscle implies a diversity of receptors and transduction mechanisms.

Major factors affecting arteriolar radius

From the biologically active substances produced from arachidonic acid which are listed below, select which is a vasodilator and platelet aggregation inhibitor produced by endothelial and smooth muscle cells

A Thromboxane A2

B Lipoxin A

C Lipoxin B

D Leukotriene C4

E Leukotriene D4

F Leukotriene B4

G Leukotriene F4

H Leukotriene E4

I Thromboxane B2

J Prostacyclin (PGI2)

From the biologically active substances produced from arachidonic acid that are listed below, select which one is synthesized by platelets and promotes vasoconstriction.

A Thromboxane A2

B Lipoxin A

C Lipoxin B

D Leukotriene C4

E Leukotriene D4

F Leukotriene B4

G Leukotriene F4

H Leukotriene E4

I Thromboxane B2

J Prostacyclin (PGI2)

Capillaries （毛细血管）

• Main function:

Exchange of nutrients and metabolic end products

Capillaries lack smooth muscle, but contraction/relaxation of circular smooth muscle in upstream metarterioles and precapillary sphincters determine the volume of blood each capillary receives.

The capillary is the primary point exchange between the blood and the interstitial fluid (ISF).

Intercellular clefts assist the exchange.

Capillary walls are a singleendothelial cell in thickness.

Structure of capillary wall

•Continuous: found in muscle, skin, lung, central nervous system

•Fenestrated: found in exocrine glands, renal glomeruli, intestinal mucosa

•Discontinuous: found in liver, spleen, bone marrow

Structure of the capillary wall

Six balls in per minute

mandates six balls out per minute.

Therefore, the velocity of the balls in the smaller tubes is slower.

Relationship between total cross-sectional area and flow velocity

There are many, many capillaries, each with slow-moving blood in it, resulting in adequate time and surface area for exchange between the capillary blood and the ISF.

• Diffusion

• Pinocytosis

• Filtration and

Reabsorption

Movement of fluid and solutes into the blood is called absorption.

Absorption

Filtration

Movement of fluid and solutes out of the blood is called filtration.

Net filtration pressure (or Effective filtration pressure)

EFP + Filtration

EFP - Reabsorption

EFP

Pc

Dynamic changes in vasodilation/vasoconstriction in thearterioles regulate downstream pressures and flow rates.

Effects of arteriolar vasodilation or vasoconstriction on capillary blood pressure

In which of the following lists of blood vessels is the sequence of vessels arranged from highest to lowest total cross-sectional area in the body?

A Arteries, arterioles, capillaries, veins

B Arterioles, capillaries, arteries, veins

C Capillaries, arterioles, veins, arteries

D Veins, capillaries, arterioles, arteries

E Arteries, veins, arterioles, capillaries

Venous pressure and venous return（静脉血压与静脉回流）

• Venous pressure

– Peripheral venous pressure （外周静脉压）──

the pressure in the peripheral veins

– Central venous pressure (CVP ，中心静脉压 )──

the pressure in the thoracic vena cava & the right

atrium 4~12cmH2O

Central venous pressure measurements were obtained for three astronauts (indicated by different colors). Notice the dramatic CVP changes that occurred during launch as well as when the astronauts arrived in space.

Measurement of central venous pressure

Jugular venous pressure is a clinical measure of central venous pressure. It is the height of the pulsating column of blood in the great veins draining into the right atrium and, in malaria, is a useful measure of over- or under-hydration (hyper- or hypovolaemia).

Jugular venous pressure is the vertical distance, measured in cm, between the venous pulsation in the neck and the sternal angle (junction of the second rib with the sternum) when the patient is propped up on pillows at 45 to the horizontal. In this position, the sternal angle marks the level of the right atrium. The height of the jugular venous pressure is normally 4–5 cm. In order to measure it, the patient should be made as comfortable and relaxed as possible. It is difficult or impossible to identify venous pulsation if the neck muscles are contracted. Try to achieve good (oblique) lighting of the neck. Look for the jugular venous pulse in the internal jugular vein or its external jugular tributaries on both sides of the neck with the patient's chin tilted up and slightly away from you. The following characteristics help to distinguish jugular venous pulsation from carotid arterial pulsation. The jugular venous pulse:

•has two waves for every single carotid artery pulsation; make this comparison by gently palpating the carotid pulse on the opposite side of the neck; •falls with inspiration and rises with expiration (except where there is cardiac tamponade); •can be obliterated by pressing firmly but gently with the back of the index finger placed horizontally just above the clavicle at the root of the neck; •may be visible only when the patient is lying flat (in cases of hypovolaemia) or when the patient is sitting upright at 90 (for example, in severe congestive cardiac failure); •is usually impalpable.

At rest, approx. 60% of the total blood volume is in the veins. Sympathetically mediated venoconstriction can substantially increase venous return to the heart.

Determinants of venous pressure

• Contraction of venous smooth muscle

–Sympathetic neurons

–Hormonal and paracrine vasodilators and vasoconstrictors

• Skeletal muscle pump

• Respiratory pump

Venous valve

Varicose vein （曲张静脉）

Varicose vein

great saphenous vein

Venous flow is assisted by the skeletal muscle pumpmechanism working in combination with one-way valves.

Respiratory activity (Respiratory pump)

Alterations in “venous return” alter end-diastolic volume (EDV);increased EDV directly increases stroke volume and cardiac output.

• The lymphatic

system is a network

of small organs

(lymph nodes) and

tubes (lymphatic

vessels) through

which lymph flows

The Lymphatic System（淋巴系统）

Lymphatic fluid, formed by the slight mismatch between filtration and absorption in the capillaries, returns to the blood in the veins.

Terminal lymphatics

Lymphatic pump

Relation between interstitial fluid pressure and lymph flow

• Absorption of proteins

• Transportation of fat and other nutrients

• Balance between plasma and interstitial fluid

• Protection

Significance of lymphatic return

Elephantiasis（象皮肿）Chronic, often extreme enlargement and hardening of cutaneous and subcutaneous tissue, especially of the legs and external genitals, resulting from lymphatic obstruction and usually caused by infestation of the lymph glands and vessels with a filarial worm.

Elephantiasis

Also known as lymphatic filariasis, this condition occurs when parasitic worms (any of several types of filaria worms) infest the lymphatic system.  The filaria are transmitted by mosquitoes to the blood and can build a population in the lymph nodes, blocking fluid drainage from arms, legs, genitals, or breasts.  It is called elephantiasis (literally, "elephant condition") because in extreme cases, the arms and legs look like the limbs of an elephant. Elephantiasis affects over a 100 million people around the world.  However, most cases are not as extreme as in this photo!

http://upload.wikimedia.org/wikipedia/commons/1/19/Filariasis_01.png

Lymph flow from the foot is:

A Increased when an individual rises from the supine to the standing position.

B Increased when the foot is massaged.

C Increased when capillary permeability is decreased.

D Decreased when the valves of the leg veins are incompetent.

E Decreased in exercise.

A 68-year-old Asian female presents to your practice with severe swelling of the left leg. The right leg appears normal. All other tests are normal except for an eosinophilia noted on CBC. You suspect lymphatic blockage, possibly due to parasitism. Which of the following contributes to circulation of lymph through the lymphatic system?

A Decreased interstitial fluid pressure

B Intrinsic pumping by the collecting lymphatics

C Negative pressure at the termination of the thoracic duct

D Protein in the interstitial fluid

E Decreased arterial blood pressure

A summary of dynamic changes in MAP and TPR.

Blood loss causes a reduction in MAP, which, if left unchecked, would result in rapid and irreversible damage to the brain and the heart.

The End.