Cardiovascular Physiology (??????)

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Cardiovascular Physiology(??????)

• Qiang XIA (??), PhD
• Department of Physiology
• Room C518, Block C, Research Building, School of
  Medicine
• Tel [phone]
• Email xiaqiang_at_zju.edu.cn

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Vascular Physiology(?????)
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?
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Lecture Outline

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

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Functional parts of blood vessels

• Elastic vessels (Windkessel vessels)
• (????)
• Resistance vessels (Precapillary resistance
  vessels)(????)
• Exchange vessels(????)
• Capacitance vessels(????)

• Distribution vessels(????)
• Shunt vessels(????)

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Hemodynamics(?????)

• Blood flow
• Q DP/R (P1-P2)/R

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Q cardiac output, 5 L/min R total peripheral
resistance PA aortic pressure

• Q PA/R

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Resistance of blood flow
Poiseuille Law QpDPr4/8hL h viscosity r
radius of the vessel L length of the vessel
R 8hL/pr4
Q DP/R
Jean Louis Marie Poiseuille \pwä-'z?i\ (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.
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r main determinant of blood flow
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• 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

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• 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.

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Arteries
Arterial blood pressure(????)
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Blood pressure measurement1. Direct (invasive)
measurement technique
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2. Indirect (non-invasive) measurement technique
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Systolic pressure (SP,???) the maximum arterial
pressure reached during peak ventricular
ejection Diastolic pressure (DP,???) the minimum
arterial pressure just before ventricular
ejection begins Pulse pressure (PP,??) the
difference between SP and DP Mean arterial
pressure (MAP,?????) the average pressure in the
cardiac cycle (DP1/3PP)
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• Mean arterial pressure (MAP)

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To estimate systolic and diastolic pressures,
pressure is released from an inflatable cuff on
the upper arm while listening as blood flow
returns to the lower arm.
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Click here to play the Sphygmomanometry Flash
Animation
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Classification of blood pressure for adults age
18 years and older
Blood Pressure Classification Chart Blood Pressure Classification Chart Blood Pressure Classification Chart
Category Systolic (mm Hg) Diastolic (mm Hg)
Normal Lower than 120 Lower than 80
Prehypertension 120 - 139 80 - 89
Hypertension   Hypertension   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 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 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.
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• Factors affecting arterial blood pressure
• Stroke volume
• Heart rate
• Peripheral resistance
• Elastic vessels
• Blood volume

Ventricular ejection
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• Q PA/R

Q cardiac output (CO) R total peripheral
resistance (SVR) PA aortic pressure (MAP)
MAP CO ? SVR
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The blood moved in a single 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
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Arterial pulse(????)
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In response to the pulsatile contraction of the
heart pulses of pressure move throughout the
vasculature, decreasing in amplitude with
distance
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Arterial pulse recorded in different vessels
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Arterial pulse recorded under different
conditions
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Clinical Application of Arterial Pulse

• ?

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Systematic examination of pulses Systematic examination of pulses 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/
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Microcirculation(???)
Function Transfer of substances between blood
the tissues
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Structure of microcirculation
A-V shunt
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3 pathways

• Circuitous channel (Nutritional channel)(????)

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• Thoroughfare channel(????)

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• Arteriovenous shunt (A-V shunt)(?-????)

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

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Arterioles(???)

• 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

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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 a1 and a2
  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

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Dynamic adjustments in the blood distribution to
the organs is accomplished by relaxation and
contraction of circular smooth muscle in the
arterioles.
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Click here to play the Arteriolar Radius Blood
Flow Flash Animation
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Click here to play the Arteriolar Resistance
BP Flash Animation
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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(????)
• Flow autoregulation(??????)
• Reactive hyperemia(?????)
• Local response to injury(????????)

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

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• 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

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Extrinsic Control

• Sympathetic nerves(????)
• Parasympathetic nerves(?????)
• Noncholinergic, nonradrenergic autonomic neurons
  (NO or other noncholinergic vasodilator
  substances)(NANC)
• Hormones (epinephrine, angiotensin II,
  vasopressin, atrial natriuretic peptide)

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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.
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Renin-angiotensin system(??-???????)
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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
angiotensin II-generating enzyme
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Robert Toto Biff F. Palmer. Am J Nephrol
200828372380
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Vasopressin(?????)
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Endothelium-derived vasoactive substances

• Vasodilator factors
• PGI2 prostacyclin(????)
• EDRF (endothelium-derived relaxing factor, nitric
  oxide)
• EDHF (endothelium-dependent hyperpolarizing
  factor)

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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
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• 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.
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• Vasoconstrictor factors Endothelin-1(???-1)

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Major factors affecting arteriolar radius
Diversity among signals that influence
contraction/relaxation in vascular circular
smooth muscle implies a diversity of receptors
and transduction mechanisms.
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• 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)

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• 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)

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Capillaries(????)

• Main function
• Exchange of nutrients and metabolic end products

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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.
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Capillary walls are a single endothelial cell
in thickness.
The capillary is the primary point exchange
between the blood and the interstitial fluid
(ISF). Intercellular clefts assist the exchange.
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Structure of capillary wall
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Structure of the 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

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Relationship between total cross-sectional area
and flow velocity
Six balls in per minute mandates six balls
out per minute. Therefore, the velocity of the
balls in the smaller tubes is slower.
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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.
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• Diffusion
• Pinocytosis
• Filtration and Reabsorption

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Net filtration pressure (or Effective filtration
pressure)
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EFP ?Filtration EFP - ? Reabsorption
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Click here to play the Fluid Change Across
Capillary Wall Flash Animation
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Effects of arteriolar vasodilation or
vasoconstriction on capillary blood pressure
Dynamic changes in vasodilation/vasoconstriction
in the arterioles regulate downstream pressures
and flow rates.
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• 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

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Venous pressure and venous return (?????????)
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• Venous pressure
• Peripheral venous pressure(?????)--
• the pressure in the peripheral veins
• Central venous pressure (CVP,?????)--
• the pressure in the thoracic vena cava the
  right atrium 412cmH2O

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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.
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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 45 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.

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

• Contraction of venous smooth muscle
• Sympathetic neurons
• Hormonal and paracrine vasodilators and
  vasoconstrictors
• Skeletal muscle pump
• Respiratory pump

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Venous valve
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Varicose vein(????)
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Varicose vein
great saphenous vein
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Venous flow is assisted by the skeletal muscle
pump mechanism working in combination with
one-way valves.
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• Respiratory activity (Respiratory pump)

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Alterations in venous return alter
end-diastolic volume (EDV) increased EDV
directly increases stroke volume and cardiac
output.
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The Lymphatic System (????)

• The lymphatic system is a network of small organs
  (lymph nodes) and tubes (lymphatic vessels)
  through which lymph flows

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Lymphatic fluid, formed by the slight mismatch
between filtration and absorption in the
capillaries, returns to the blood in the veins.
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Terminal lymphatics
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Lymphatic pump
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Relation between interstitial fluid pressure and
lymph flow
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Significance of lymphatic return

• Absorption of proteins
• Transportation of fat and other nutrients
• Balance between plasma and interstitial fluid
• Protection

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Elephantiasis (???) 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.
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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!
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• 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.

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• 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

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A summary of dynamic changes in MAP and TPR.
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Blood loss causes a reduction in MAP, which, if
left unchecked, would result in rapid and
irreversible damage to the brain and the heart.
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The End.