Cardiovascular Phsiology

2. 2

3. Fig. 2 A - Valve partly open Fig. 2B - Valve almost completely closed
Photographs of the pulmonary valve viewed from the top—i.e., from the pulmonary trunk looking down
into the right
ventricle.
Fig. 2 A - On the left the valve is in the process of opening as blood flows through it from the right
ventricle into the pulmonary trunk
Fig. 2 B - On the right, the valve is in the process of closing, the cusps being forced together by the
downward pressure of the blood— i.e., by the pressure of the blood in the pulmonary trunk being greater
than the pressure in the right ventricle.
From R. Carola, J. P. Harley, and C. R. Noback, “Human Anatomy and Physiology,” McGraw-Hill, New
York, 1990 (photos by Dr. Wallace McAlpine).
3

4.  Arranged in layers tightly bound together
 Cardiac muscle completely encircles blood-filled chambers
 Contraction of these muscles mimic a squeezing fist
 Converts chemical energy in the form of ATP into force
generation
 Conducting system are in contact with cardiac muscle cells via
gap junctions
 Some cells in the atria secretes a peptide hormone called the
atrial natriuretic peptide (ANP)
 ANP is a powerful vasodilator, and a protein (polypeptide) hormone secreted by
heart muscle cells. It is involved in the homeostatic control of body water, sodium,
potassium and fat (adipose tissue).
 It is released by muscle cells in the upper chambers (atria) of the heart (atrial
myocytes), in response to high blood pressure. ANP acts to reduce the water,
sodium and adipose loads on the circulatory system, thereby reducing blood
pressure.[1]
4

5. 5
Cardiac Muscle
Fig. 3 fist simulates the contracting of the heart
muscle
Web Ref.- fist simulates the
contracting of the heart muscle
acofchattanooga.com
On average the
heart beats approximately:
~ 70 beats per minute
~ 4,200 beats per hour
~ 100,800 per day
~ 705,600 per week
~ 2,822,400 per month
~ 33,868,800 per year (multiply
this number by your age to get an
approximate
total of how many times your
heart has beat thus far).

6. Cardiac Muscle
 Cardiac muscles are striated muscles due to regular
repeating sarcomeres composed of myosin .
 Troponin and tropomysin are present
 Involuntarily controlled
 Arranged in tightly bound layers
 Semi-spindle in shape and short
 contain intercalated discs and T-tubules, which has
sarcoplasmic reticulum lateral sacs that store
calcium
 Completely encircle blood filled chambers.
 An excitable tissue, converts chemical energy in the
form of ATP
 Consists of a conducting system that are in contact
with cardiac muscle cells via gap junctions
 are relatively small (100 µm long & 20 µm wide)
 Have 1 nucleus
Smooth & Skeletal Muscle
 Smooth muscle contains actin &
myosin & contract by a sliding filament
mechanism
 Smooth muscle cells are spindle shaped
and lack striations.
 Smooth muscle has a single nucleus &
is capable of cell division
 Skeletal muscles are striated muscles.
 Somatic nervous system controlled
 Cylindrical in shape
 An excitable tissue, converts chemical
energy in the form of ATP
 Multi nucleated
6
Fig. 4 different muscle cells in the
human body
Web ref.- Cardiac muscle cells ...
nlm.nih.gov

7. Fig. 5 Diagram of an electron micrograph of cardiac muscle.
7
Electron micrograph of cardiac muscle
(Courtesy of Dr. Helen Rarick).
uic.edu

8.  Rich supply of sympathetic and parasympathetic nerve
fibers contained in the vargus nerves
 Sympathetic postganglionic fibers – innervate the
heart - releases norepinehrine
 Parasympathetic nerve fibers – terminate on cells
found in the atria – releases acetylcholine
8
The vagus nerve is either one of two cranial nerves which are extremely
long, extending from the brain stem all the way to the viscera. The vagus
nerves carry a wide assortment of signals to and from the brain, and they
are responsible for a number of instinctive responses in the body.
The vagus nerve helps to regulate heart beat, control of muscle movement
etc.
www.wisegeek.com/what-is-the-vagus-
nerve.htm

9.  The receptors for norepinehrine on cardiac muscle are mainly beta-
adrenergic.
 Beta-adrenergic blockers (β-blockers) are an important class of
drugs for the treatment of various heart diseases, including high
blood pressure, insufficiency of blood flow to the heart muscle
(angina pectoris), irregular heart beat (arrhythmias), thickened heart
muscle (hypertrophic cardiomyopathy), and decreased ability of the
heart to empty or fill normally (heart failure). β-Blockers can also
be used to treat migraine headache and increased pressure of the eye
(glaucoma). No other class of man-made drugs has had such
widespread applicability in clinical medicine.
 Ref: circ.ahajournals.org/content/107/18/e117.full
9

10.  What Is a β-Blocker?
 Hormones known as catecholamines (norepinephrine, epinephrine) activate
or stimulate specific receptors on cell surfaces, known as adrenergic
receptors. A receptor has a specific structure that allows a drug or hormone
to bind to it, similar to a key fitting in a lock.
 The catecholamines are released from nerve endings of the sympathetic
nervous system, an involuntary nerve network that enables the body to
withstand stress, anxiety, and exercise.
10

11.  β-Adrenergic receptors are found in the heart, blood vessels, and the lungs,
and can be stimulated by catecholamine binding, thus increasing the
activity of cells in the body. β-Adrenergic receptor stimulation causes an
increase in heart rate, heart muscle contraction, blood pressure, and
relaxation of smooth muscle in the bronchial tubes in the lung, making it
easier to exercise and expand the lungs.
 When β-blocking drugs are given to patients through a vein or by mouth,
they will block the access of catecholamines to their receptors so that the
heart rate and blood pressure are reduced, and the heart will pump with less
intensity. This, in turn, will reduce the oxygen needs of the heart. The
effects of β-blockers are greatest when catecholamine levels and receptor
numbers are high, as would occur during intense exercise, and are lessened
when catecholamine levels are reduced, as during sleep. β-Blockers usually
do not completely diminish the ability of the heart to respond to stress, but
instead modify the heart’s response
Ref: circ.ahajournals.org/content/107/18/e117.full
11

12.  The hormone epinephrine, from the adrenal medulla,
combines with the same receptors as norepinehrine and
exerts the same actions on the heart.
 The receptors for acetylcholine are of the muscarinic
type.
12

13. 13

14.  Heart pumps blood separately but simultaneously into
the systemic and pulmonary vessels
 The atria contracts first then the ventricles
 Contraction is triggered by depolarization of the plasma
membrane. This occurs in the sinoarterial (SA) node.
 The gap junctions allow action potentials to spread
from one cell to another resulting in excitation of all
cardiac cells.
14

15.  The SA node (normal pacemaker) discharge rate
determines heart rate
 The atrioventricular (AV) node is located at the base of
the right atrium. Here the propagation of action
potentials is relatively slow ( .1s)
 allows for artrial contraction to be completed before
ventricular excitation occurs.
15

16. 16
Diagram of the heart showing the cardiac
conduction system
nottingham.ac.uk

17. 17

18.  The resting membrane is much more permeable to K+ than Na+
 Resting potential is closer to K+ potential than to Na+ equilibrium
potential
 Due mainly to opening of Na+ channels
 Na+ entry depolarizes the cell and sustains the opening of more Na+
channels in +ve feedback
 Permeability to K+ decreases as K+ channels close also contributing to
membrane permeability
 Permeability to Ca+ increases as plasma membrane open and Ca 2+ flows
into the cell.
 L-type Ca2+ channels – (long lasting)
 The flow of +ve Ca+ ions into the cell balances the flow of + K+ ions out
of the cell and keeps the membrane at the plateau value.
18

19. 19

20.  Firstly a progressive reduction in potassium
permeability has potassium channels open during
repolarization
 This gradually closes due to the membrane return to
negative potential
 The pacemaker cells open when the membrane
potential is at negative values
 These nonspecific cation channels conduct mainly an
inward depolarizing sodium current termed F-type
sodium channels.
20

21. 21

22.  T-type sodium channels (T=transient)
 Only opens briefly but contributes to an inward calcium
current and a boost to the pacemaker potential
 Depolarizing phase is caused by calcium influx through
the L-type calcium channel
 The opening of K+ channels repolarizes the membrane
 The return to negative potentials activates the
pacemaker mechanism and the cycle continues
22

23.  Tool used for evaluating the events of the heart
 Charges/currents are caused by the action potentials occurring
simultaneously in many myocardial cells.
 In a typical ECG:
1. P wave corresponds to current flow during atrial
depolarization
2. QRS complex occurs .15s later. It is the result of ventricular
depolarization. N.b differs as a result of the currents in body
fluid change direction
3. T wave the result of ventricular repolarization. Occurs at the
same time as the QRS complex
23

24. 24
The T wave is the
electrocardiographic expression
of repolarization of the ...
vetgo.com

25.  Systole – ventricular contraction and blood ejection
 Diastole – alternating period of ventricular relaxation and blood filling
 Isovolumetric ventricular contraction – ventricles contract but no blood
is ejected as volume is constant
 Ventricular ejection – rising pressure causes the aortic and pulmonary
valves to open
 Stroke volume – the volume of blood ejected from each ventricle during
systole
 Isovolumetric ventricular relaxation – valves are closed, no blood is
entering or leaving, therefore ventricular volume is not changing
 Ventricular filling – AV valves open and blood flows in from the atria
25

26. 26

27. 27

28.  The volume of blood that each ventricle pumps:
 Expressed in liters per minute (L/min)
 The volume of blood flowing through either the
systemic or pulmonary circuit per minute
 Determined by heart rate (HR) x stroke volume (SV):
CO= HR x SV
 Normal range for a resting adult: 72 beats x
.07L=5.0L/min
28

29.  Activity in the parasympathetic nerves causes the heart
rate to decrease
 Activity in the sympathetic nerves causes the heart rate
to increase
 Epinephrine speeds the heart by acting on the beta
adrengenic receptors in the SA node
 Sensitivity to change in body temperature, plasma
electrolyte conc. Other hormones and adenosine
29

30. Three dominant factors affect stroke volume
 Changes in the end diastolic volume (the volume of blood in the ventricles
before contraction known as preload)
 Changes in the magnitude of the sympathetic nervous system input to the
ventricles
 Changes in afterload i.e. the arterial pressures against which the ventricles
pump
30

31.  A length tension relationship as the end diastolic
volume is a major determinant of how stretched the
ventricular sarcomeres are before contraction.
 An increase in venous return automatically forces an
increase in cardiac output by increasing end-diastolic
volume and stroke volume
IMPORTANT:
 The equality of the right and left output must be
maintained
31

32. 32

33. BLOOD CELLS
PLASMA
ARTERIES
ARTERIOLES
CAPILLARIES
VEINS

34. Blood is defined as a mixture of cellular components
suspended in a fluid - plasma.

35. • Average volume of blood: 5–6 L for males; 4–5 L for females
– Hypovolemia - low blood volume
– Hypervolemia - high blood volume
• Osmolarity = 300 mOsm or 0.3 Osm similar to that of coconut water
– This value reflects the concentration of solutes in the plasma
• Salinity = 0.85% ; reflects the concentration of NaCl in the blood
• Temperature is 38C, slightly higher than “normal” body temperature
• Viscosity (thickness) - 4 - 5 (where water = 1)
• The pH of blood is 7.35–7.45; x = 7.4

36. 1. Transport:
–Oxygen from the lungs and nutrients from
the digestive tract
–Metabolic wastes from cells to the lungs and
kidneys for elimination
–Hormones from endocrine glands to target
organs

37. 2. Blood maintains:
◦ Body temperature by absorbing and distributing
heat to other parts of the body
◦ Normal pH in body tissues using buffer systems
◦ Adequate fluid volume in the circulatory system

38. 3. Blood protection:
 Blood prevents blood loss by:
◦ Activating plasma proteins and platelets
◦ Initiating clot formation when a vessel is broken
 Blood prevents infection by:
◦ Synthesizing and utilizing antibodies
◦ Activating complement proteins
◦ Activating WBCs to defend the body against
foreign invaders

39.  Blood is the body’s only fluid tissue
 2 major components
Liquid = plasma (55%)
Formed elements (45%)
 Erythrocytes, or red blood cells
 Leukocytes, or white blood cells
 Platelets - fragments of megakaryocytes in marrow

41.  Liquid part of blood
- Pale yellow made up of 91% water, 9% other
 Three types of plasma proteins:
- Albumin: Important in regulation of water
movement between tissues and blood
- Globulins: Immune system or transport molecules
- Fibrinogen: Responsible for formation of blood
clots

42. • Organic nutrients – glucose, amino acid and
carbohydrates
• Electrolytes – sodium, calcium, potassium,
chloride and bicarbonate
• Non-protein nitrogenous substances – lactic
acid, creatinine and urea
• Respiratory gases – oxygen and carbon dioxide

43. • 7.5m in diameter
• One RBC contains 280 million hemoglobin molecules
• Life span 100-120 days and then destroyed in spleen
• Men- 5 million cells/mm3
• Women- 4.5 million cells/mm3
• Components : Hemoglobin, Lipids, ATP and carbonic anhydrase
• Function
Transport oxygen from lungs to tissues and carbon dioxide from
tissues to lungs

44. • Structure:
Biconcave- Folding increases surface area (30% more surface area)
- plasma membrane contains spectrin
 Give erythrocytes their flexibility
Anucleate-no centrioles, no organelles
◦ End result - no cell division
◦ No mitochondria means they generate ATP anaerobically
 Prevents consumption of O2 being transported

45.  Consists of:
1. Globin molecules(4): Transport carbon dioxide and nitric
oxide
2. Heme molecules(4): Transport oxygen
 Iron is required for oxygen transport

46.  Production of red blood cells
- Stem cells to proerythroblasts to early
erythroblasts intermediate to late to reticulocytes
 Erythropoietin: Hormone to stimulate RBC
production

47. 1. Anemia - when blood has low O2 carrying capacity insufficient
RBC or iron deficiency. Factors that can cause anemia- exercise,
B12 deficiency
2. Polycythemia - excess of erythrocytes, increase viscosity of
blood 8-11 million cells/mm3. Usually caused by cancer, tissue
hypoxia, dehydration; however, naturally occurs at high elevations
4. Malaria - Disease that attacks the RBC, causes high fever

48.  Leukocytes, the only blood components that are
complete cells: 4,800 - 10,000/cubic millimeter
–Protect the body from infectious microorganisms and
remove dead cells and debris
–Can leave capillaries via diapedesis
–Move through tissue spaces (amoeboid motion)
–Many are phagocytic (possess numerous lysosomes)

49.  Leukocytosis – WBC count over 11,000/mm3
–Normal response to bacterial or viral invasion
 Leukopenia - a decrease in WBC count below
4,800/mm3
• Leukemia - a cancer of WBC
• Two major types of leukocytes
–Granulocytes: Neutrophils, Eosinophils, Basophils
–Agranulocytes: Monocytes, Lymphyocytes

50. 1. Neutrophils- Account for 65-75% of total WBC’s
• Neutrophils have two types of granules that:
– Take up both acidic and basic dyes
– Give the cytoplasm a lilac color
– Contain peroxidases, hydrolytic enzymes, and defensins
(antibiotic-like proteins)
• Neutrophils are our body’s bacteria slayers

51. 2. Eosinophils- accounts for 1–4% of WBCs
◦ Have red-staining, bilobed nuclei
◦ Have red to crimson granules
◦ Function:
 Lead the body’s counterattack against parasitic infections
 Lessen the severity of allergies by phagocytizing immune
complexes (ending allergic reactions)

52. 3. Basophils - account for 0.5-1% of all WBCs
– Have U- or S-shaped nuclei with two or three conspicuous
constrictions
– Are functionally similar to mast cells
– Have large, purplish-black (basophilic) granules that contain
histamine
• Histamine – inflammatory chemical that acts as a vasodilator
and attracts other WBCs (antihistamines counter this effect)

53. 4. Lymphyocytes - account for 20-25% or more of WBCs and:
– Have large, dark-purple, circular nuclei with a thin rim of blue
cytoplasm
– Are found mostly enmeshed in lymphoid tissue (some circulate
in the blood)
• Most important cells of the immune system
• There are two types of lymphocytes: T cells and B
cells
– T cells - attack foreign cells directly
– B cells give rise to plasma cells, which produce antibodies

54. 5. Monocytes account for 3–7% of leukocytes
◦ They are the largest leukocytes
◦ They have purple-staining, U- or kidney-shaped nuclei
◦ They leave the circulation, enter tissue, and differentiate into
macrophages

55.  All leukocytes originate from hemocytoblasts
- The mother of all blood stem cells
 Hemocytoblasts differentiate into myeloid stem cells and
lymphoid stem cells
- Myeloid stem cells become myeloblasts or monoblasts
Granulocytes form from myeloblasts
Monoblasts enlarge and form monocytes
- Lymphoid stem cells become lymphoblasts
Lymphoblasts develop into lymphocytes

57.  Leukemia refers to cancerous conditions involving white
blood cells
 Leukemias are named according to the abnormal white
blood cells involved
◦ Myelocytic leukemia – involves myeloblasts
◦ Lymphocytic leukemia – involves lymphocytes
 Acute leukemia involves blast-type cells and primarily
affects children
 Chronic leukemia is more prevalent in older people

58.  Platelets are fragments of megakaryocytes
 Their granules contain serotonin, Ca2+, enzymes, ADP,
and platelet-derived growth factor
 Platelets function in the clotting mechanism by forming a
temporary plug that helps seal breaks in blood vessels
 Platelets not involved in clotting are kept inactive by
nitric oxide (NO) and prostaglandins

60.  Arteries are muscular blood vessels that carry
blood away from the heart(oxygenated and
deoxygenated blood) .
 The pulmonary arteries will carry
deoxygenated blood to the lungs
and the sytemic arteries will carry oxygenated
blood to the rest of the body.

61.  Arteries have a thick wall that consists of three layers.
- The inside layer is called the endothelium
- the middle layer is mostly smooth muscle
- the outside layer is connective tissue.
 The artery walls are thick so that when blood enters
under pressure the walls can expand.

62.  When the left ventricle ejects blood into the aorta, the
aortic pressure rises.
 The maximal aortic pressure following ejection is termed
the systolic pressure (Psystolic).
 As the left ventricle is relaxing and refilling, the pressure
in the aorta falls.
 The lowest pressure in the aorta, which occurs just before
the ventricle ejects blood into the aorta, is termed the
diastolic pressure (Pdiastolic )

63.  When blood pressure is measured using a
sphygmomanometer, the upper value is the systolic pressure
and the lower value is the diastolic pressure.
 Normal systolic pressure is 120 mmHg or less, and normal
diastolic pressure is 80 mmHg or less.
 The difference between the systolic and diastolic pressures is
the aortic pulse pressure, which typically ranges between 40
and 50 mmHg. The mean aortic pressure(Pmean) is the
average pressure (geometric mean) during the aortic pulse
cycle.

64.  Arterial pressure is measured using a sphygmomanometer (i.e.
blood pressure cuff) on the upper arm.
 The systolic and diastolic pressures that are measured represent
the pressure within the brachial artery, which is slightly
different than the pressure found in the aorta or the pressure
found in other distributing arteries.
 As the aortic pressure pulse travels down the aorta and into
distributing arteries, there are characteristic changes in the
systolic and diastolic pressures, as well as in the mean pressure.

65.  The systolic pressure rises and the diastolic pressure falls,
therefore the pulse pressure increases, as the pressure pulse
travels away from the aorta.
 This occurs because of reflective waves from vessel
branching, and from decreased arterial compliance (increased
vessel stiffness) as the pressure pulse travels from the aorta
into systemic arteries. There is only a small decline in mean
arterial pressure as the pressure pulse travels down
distributing arteries due to the relatively low resistance of
large distributing arteries.

66.  An arteriole is a small artery that extends and leads to
capillaries.
 Arterioles have thick smooth muscular walls. These
smooth muscles are able to contract (causing vessel
constriction) and relax (causing vessel dilation).
 This contracting and relaxing affects blood pressure; the
higher number of vessels dilated, the lower blood
pressure will be.

67. Local Controls: are mechanisms independent of hormones and
nerves. Hyperemia occurs when blood flow in an organ
increases by arteriolar dilation in response to an increase in
metabolic activity that causes local changes such as decrease
in O2, increase in CO2 and H+.
Extrinsic Controls: Sympathetic nerves that provide a rich
supply of impulses to arterioles. Release norepinephrine and
cause vasoconstriction
 Hormones such as vasopressin (from posterior pituitary) and
angiotension II (from liver) constrict arterioles.

68.  Heart
- High intrinsic tone; oxygen extraction is very high at rest, and so
flow must increase when oxygen consumption increases if
adequate oxygen supply is to be maintained.
- Controlled mainly by local metabolic factors, particularly
adenosine, and flow autoregulation; direct sympathetic influences
areminor and normally overridden by local factors.
- Vessels are compressed during systole, and so coronary flow
occurs mainly during diastole.

69.  Skeletal Muscle
- Controlled by local metabolic factors during exercise.
- Sympathetic nerves cause vasoconstriction (mediated by
alpha-adrenergic receptors) in reflex response to
decreased arterial pressure.
- Epinephrine causes vasodilation, via beta-adrenergic
receptors, when present in low concentration and
vasoconstriction, via alphaadrenergic receptors, when
present in high concentration.

70.  Kidneys
- Flow autoregulation is a major factor.
- Sympathetic nerves cause vasoconstriction, mediated by
alpha-adrenergic receptors, in reflex response to
decreased arterialpressure and during stress.
Angiotensin II is also a major vasoconstrictor. These
reflexes help conserve sodium and water.

71.  Lungs
- Very low resistance compared to systemic circulation.
- Controlled mainly by gravitational forces and passive
physical forces within the lung.
- Constriction, mediated by local factors, occurs in
response to low oxygen concentration—just opposite
that which occurs in thesystemic circulation.

72.  Brain
- Excellent flow autoregulation.
- Distribution of blood within the brain is controlled by
local metabolic factors.
- Vasodilation occurs in response to increased
concentration of carbon dioxide in arterial blood.
- Influenced relatively little by the autonomic nervous
system.

73.  GI Tract, Spleen, Pancreas, and Liver
- Actually two capillary beds partially in series with each other; blood
from the capillaries of the GI tract, spleen, and pancreas flows via the
portal vein to the liver. In addition, the liver also receives a separate
arterial blood supply.
- Sympathetic nerves cause vasoconstriction, mediated by alpha-
adrenergic receptors, in reflex response to decreased arterial pressure
and during stress. In addition, venous constriction causes displacement
of a large volume of blood from the liver to the veins of the thorax.
- Increased blood flow occurs following ingestion of a meal and is
mediated by local metabolic factors, neurons, and hormonessecreted by
the GI tract.

74.  SKIN
- Controlled mainly by sympathetic nerves, mediated by alpha-
adrenergic receptors; reflex vasoconstriction occurs in
response to
decreased arterial pressure and cold, whereas vasodilation occurs
in response to heat.
- Substances released from sweat glands and noncholinergic,
nonadrenergic neurons also cause vasodilation.
- Venous plexus contains large volumes of blood, which
contributes to skin color.

75.  Capillaries are the smallest of a body’s vessels; they connect arteries and veins, and
most closely interact with tissues.
 They are very prevalent in the body; total surface area is about 6,300 square meters.
Because of this, no cell is very far from a capillary, no more than 50 micrometers
away.
 The walls of capillaries are composed of a single layer of cells, the endothelium,
which is the inner lining of all the vessels. This layer is so thin that molecules such
as oxygen, water and lipids can pass through them by diffusion and enter the tissues.
 Waste products such as carbon dioxide and urea can diffuse back into the blood to
be carried away for removal from the body.


76.  The "capillary bed" is the network of capillaries present
throughout the body. These beds are able to be “opened” and
“closed” at any given time, according to need.
 This process is called auto-regulation and capillary beds usually
carry no more than 25% of the amount of blood it could hold at
any time.
 The more metabolically active the cells, the more capillaries it
will require to supply nutrients.
 Blood velocity decreases as blood passes through the huge cross
sectional area of a capillary.

77.  There are three basic mechanisms by which substances move across
capillary walls to enter or leave the interstitial fluid:
(1) Diffusion is the only important means by which net
movement of nutrients, oxygen and metabolic end products can
occur. Intercellular clefts allow the passage of polar molecules.
Brain capillaries, however, are tight with no intercellular clefts.
Liver capillaries are leaky with large clefts for movement of
substances. The trans-capillary diffusion gradient is setup by
utilization or production of a substance.

78. (2) Vesicle transport allows for the passage of
molecules via endo- and exocytosis.
(3) Bulk flow enables protein-free plasma to move
from capillaries to the interstitial fluid due to hydrostatic
pressure. This is opposed by an osmotic force, resulting
from differences in protein concentration that tends to
move interstitial fluid into the capillaries. Bulk flow also
serves to function in distributing extracellular fluid.

80.  Veins carry blood to the heart.
 The pulmonary veins will carry oxygenated blood to the
heart awhile the systemic veins will carry deoxygenated
to the heart.
 Most of the blood volume is found in the venous system;
about 70% at any given time.

81.  The veins outer walls have the same three layers as the
arteries, differing only because there is a lack of smooth
muscle in the inner layer and less connective tissue on the
outer layer.
 Veins have low blood pressure compared to arteries and
need the help of skeletal muscles to bring blood back to
the heart.

82.  Most veins have one-way valves called venous valves to prevent
backflow caused by gravity.
 They also have a thick collagen outer layer, which helps maintain
blood pressure and stop blood pooling.
 If a person is standing still for long periods or is bedridden, blood
can accumulates in veins and can cause varicose veins.
 The hollow internal cavity in which the blood flows is called the
lumen.

83.  A muscular layer allows veins to contract, which puts
more blood into circulation.
 Veins are used medically as points of access to the blood
stream, permitting the withdrawal of blood specimens for
testing purposes, and enabling the infusion of fluid,
electrolytes, nutrition, and medications.

84.  By the time blood has passed from the capillaries into the venous
system the pressure has dropped significantly.
 The average blood pressure in the venous system is only 2 mmHg
(millimeters of mercury) as compared to an average of 100 mmHg
in the arterial system.
 The low venous pressure is barely adequate to drive blood back to
the heart, particulary from the legs.
 Other mechanisms are needed to aid in the return of blood to the
heart.

85.  The flow of venous blood back to the heart is increased
by the sympathetic nervous system, the skeletal muscle
pump, and the respiratory pump.
 Veins are enervated by sympathetic motor neurons.
 Sympathetic input causes vasoconstriction, which
increases pressure, which drives blood back to the heart.
 When the body needs to mobilize more blood for
physical activity, the sympathetic nervous system
induces vasoconstriction of veins.

86.  Veins pass between skeletal muscles.The contraction of skeletal
muscle squeezes the vein, thus increasing blood pressure in that
section of the vein.
 Pressure causes the upstream valve (furthest from the heart) to
close and the downstream valve (the one closest to the heart) to
open. Repeated cycles of contraction and relaxation, as occurs
in the leg muscles while walking, effectively pumps blood back
to the heart.

87.  While the contraction of skeletal muscle in the legs drives venous
blood out of the lower limbs, the act of breathing helps to drive
venous blood out of the abdominal cavity.
 As air is inspired, the
diaphragm descends and abdominal
pressure increases.
 The increasing pressure squeezes veins
and moves blood back toward the heart.
 The rhythmic movement of venous blood causes by the act of
breathing is called the respiratory pump.
 Venous valves prevent backflow of blood in veins

88. The lymphatic system
Blood volume and long-term regulation of arterial pressure
Counteracting the effects of blood loss through
haemorrhage

89.  The lymphatic system is a network of small organs (lymph
nodes) and tubes (lymphatic vessels/lymphatics) through
which a fluid derived from interstitial fluid (lymph) flows.
 Fig.1illustrates the lymphatic system (green) in relation to
the cardiovascular system (blue and red).
 The lymphatic system is a one-way system whose vessels
constitute a route for the movement of interstitial fluid to
the cardiovascular system. As such it is technically not a
part of the cardiovascular system.

91.  The lymphatic capillaries are the first of the lymphatic
vessels. Numerous lymphatic capillaries are present
in the interstitium of nearly all organs and tissues
and are completely distinct from blood vessel
capillaries.
 They are tubes consisting of a single layer of
endothelial cells resting on a basement membrane,
but have large water-filled channels that are
permeable to all interstitial fluid constituents
including protein.

92.  The interstitial fluid continuously enters the lymphatic
capillaries in small amounts by bulk flow.
 The fluid now known as lymph then flows from the
capillaries into the next set of lymphatic vessels which
converge to from larger and larger lymphatic vessels. At
various points lymph flows through the lymph nodes.
 The entire network ends in two large lymphatic ducts
which drain into the subclavian veins in the lower neck.
This is the point of entry into the cardiovascular system.

93.  The movement of lymph into the cardiovascular system is
very important because the amount of fluid filtered out of all
the blood-vessel capillaries except those in the kidney,
exceeds that reabsorbed by approximately 4L per day. The
lymphatic system returns this 4L also containing leaked
proteins to the blood.
 Failure of the lymphatic system allows the accumulation of
excessive interstitial fluid resulting in massive swelling of the
area involved and is termed edema.
 The lymphatic system also provides the pathway by which
fats absorbed from the gastrointestinal tract reach the blood.

94.  The lymphatic vessels beyond the lymphatic capillaries propel
the lymph within them by their own contractions. The smooth
muscle in the walls exerts a pump-like action by inherent
rhythmical contractions.
 The lymphatic vessels have valves similar to those in veins so
contractions produce a one-way flow towards the point at
which the lymphatics enter the circulatory system.
 The lymphatic-vessel smooth muscle is responsive to stress.
It is inactive when there is no accumulation of interstitial fluid
and hence no entry of lymph into the lymphatics.

95.  Increased fluid filtration out of blood vessel
capillaries increases lymph formation.
 This increased fluid entering the lymphatics
stretches the walls and triggers rhythmical
contractions of the smooth muscle.
 This constitutes a negative-feedback mechanism
for adjusting the rate of lymph flow to the rate of
lymph formation and thereby preventing edema.

96.  The smooth muscle of the lymphatic vessels is
innervated by sympathetic neurons which
undergo excitation in various physiological states
such as exercise and may contribute to increased
lymph flow.
 Lymph flow is also enhanced by forces external
to the lymphatic vessels such as the skeletal
muscle pump and the respiratory pump.

97.  The mean systemic arterial pressure is the
arithmetic product of
◦ the cardiac output (the volume of blood pumped into the
artery per unit time) &
◦ the total peripheral resistance (the sum of resistances to
flow offered by all the systemic blood vessels).

98.  MAP is the major cardiovascular variable being regulated
in the systemic circulation.
 It drives blood flow through all organs except the lungs.
 Its maintenance is required for ensuring adequate blood
flow to these organs.
 The average volume of blood in the systemic arteries
(mean arterial blood volume, MABV) is determined by the
CO and TPR over time in the systemic arteries. It is this
blood volume that causes the pressure.

99.  The relationship which defines MAP as the arithmetic
product of CO and TPR can be formally derived from
the basic equation relating flow, pressure and
resistance.
◦ F = ∆P/R
◦ Therefore, ∆P = F x R
 The systemic vascular system is a continuous series
of tubes so the equation holds for the entire system,
i.e. from the arteries to the right atrium. Therefore,
o ∆P = mean systemic arterial pressure, MAP – pressure in
the right atrium
o F = the cardiac output, CO
o R = the total peripheral resistance, TPR

100.  The pressure in the right atrium is approximately
0mmHg. Thus the equation becomes
◦ MAP =CO x TPR
 An analogous equation can also be applied to
pulmonary circulation.

101.  At steady state the rate at which the heart pumps
blood into the arteries is equal to the total rate at
which blood leaves the arteries via the arterioles.
 This is analogous to a pump pushing fluid into a
container at the same rate as which the fluid leaves
the container via outflow tubes. Shown in Fig 20a
 Thus the height of the fluid in the column ∆P which
is the driving pressure for outflow remains stable.

102.  Recall
Hydrostatic Pressure = pgh
where p (rho) = density of fluid
g = acceleration due to gravity
h = height of the fluid column
 It is defined as the pressure a vertical column of fluid
exerts due to the effects of gravity.
 p and g are constants, so change in pressure is dependent
on change in height.

103.  If the steady state is disturbed by loosening the cuff on one of
the outflow tubes the radius increases reducing its resistance
and increasing its flow.
 More fluid leaves the reservoir than enters pump so the volume
and hence the height of the fluid column decreases until a new
steady state between inflow and outflow is reached.
 Thus at any given pump input change in total outflow resistance
must produce changes in the volume and hence the height
(pressure) in the reservoir once no compensatory adjustments
are made.

104. Figure 20a - Dependence of arterial blood flow
upon total arteriolar resistance
TPR is equated with Total Arteriolar Resistance

105.  During exercise skeletal-muscle arterioles dilate thereby
decreasing resistance.
 As shown in Fig.20b, if only one vascular bed (representative of
the skeletal-muscle arterioles) dilated and the CO and arteriolar
diameter remained unchanged in all the other beds (arterioles of
the other organs), the increased run-off through the skeletal-
muscle arterioles will decrease the MAP.
 To compensate for this decreased resistance the arterioles in
other organs will constrict simultaneously to increase the
resistance rendering the TPR and hence the MAP unchanged. The
brain arterioles will however remain unchanged ensuring a
constant brain blood supply.

106. Figure 20b- compensation for dilation in one bed by
constriction in others
When outflow tube1 dilates outflow tubes 2-4 are simultaneously
tightened. Outflow tube 5 remains unchanged.

107.  It is however important to note that the compensation
method previously described can only maintain the TPR
within certain limits.
 The actual case during exercise is that the skeletal muscle
arterioles will dilate so wide that even complete closure of
the other arterioles will not prevent the total outflow
resistance from falling.
 Thus this example only serves as an intuitive approach to
explain why TPR is one of the two variables that set the
MAP.

108.  Fig. 21 illustrates the grand scheme of factors that
determine the mean systemic arterial pressure. A change
in a single variable will produce a change in the mean
systemic arterial pressure by altering either cardiac output
or total peripheral resistance.
 As a specific example Fig. 22 illustrates how the decrease
in blood volume occurring during haemorrhage leads to a
decrease in the mean arterial pressure.
 Any deviation in arterial pressure like that occurring
during haemorrhage will elicit homeostatic reflexes so that
CO and/or TPR will be changed in the direction required to
minimize the initial change in arterial pressure.

109. Determinants of CO
Determinants of TPR with the addition of the
effect of hematocrit on resistance

111.  Baroreceptor reflexes bring about homeostatic adjustments to
MAP on a short-term basis (seconds to hours) i.e. they function
as short term regulators of MAP.
 They utilize mainly changes in the activity of autonomic nerves
supplying the heart and blood vessels, as well as changes in the
secretion of the hormones (epinephrine, angiotensin II, and
vasopressin) that influence these structures.
 The baroreceptor reflex is activated instantly by any blood
pressure change and attempts to restore blood pressure rapidly
towards normal. It cannot regulate on a long-term basis as
arterial baroreceptors adapt to arterial pressure once it deviates
from its normal operating point for more than a few days. They
will therefore have a decreased frequency of action potential
firing at any given pressure.

112.  Baroreceptor reflexes originate primarily with arterial receptors that respond to
changes in pressure called arterial baroreceptors. They are constituted by the
two carotid sinuses and the aortic arch baroreceptor. Afferent neurons from the
arterial baroreceptors travel to the brain stem and provide input to the neurons
of the cardiovascular control centres there.
 The carotid sinuses are located high in the neck at the point where the carotid
arteries divide.
 At the carotid sinus the artery wall is thinner and contains a large number of
branching vine-like nerve endings that are highly sensitive to stretch.

113.  The degree of wall stretching is directly related to the pressure
within the artery so the carotid sinus serves as pressure receptors, or
baroreceptors.
 The arch of the aorta is functionally similar to the carotid sinuses.
 Fig. 23 illustrates the location of the arterial baroreceptors.

115.  It is important to note that the large systemic veins the pulmonary
vessels and the walls of the heart also contain baroreceptors which
keep the brain cardiovascular control centres constantly informed
about changes in pressure in these areas thus providing a further
degree of regulatory sensitivity. They contribute a feed forward
component of arterial pressure control.
 The primary integrating centre for the baroreceptor reflexes is a
diffuse network of highly interconnected neurons called the
medullary cardiovascular centre, located in the brainstem medulla
oblongata.
 The input received by neurons in this centre determines the outflow
from the centre along neural pathways that terminate upon the cell
bodies and dendrites of the vagus (parasympathetic) neurons to the
heart and the sympathetic neurons to the heart, arterioles and veins.

116.  As illustrated in Figure 24 a decrease in sympathetic outflow to
the heart, arterioles and veins and an increase in parasympathetic
outflow to the heart results when the arterial baroreceptors
increase their rate of discharge (firing of action potentials) and
vice versa.
 Decreased arterial pressure elicits increased plasma
concentrations of the hormones angiotensin II and vasopressin
which raise arterial pressure by constricting arterioles.

117. Figure 24- Neural components of the arterial
baroreceptor reflex
If the initial changes were a decrease in arterial pressure
all the arrows in the box will be reversed.

118.  A decrease in the arterial pressure causes the discharge rate of the
arterial baroreceptors to also decrease. Thus fewer impulses
travel up the afferent nerves to the medullary cardiovascular
centre and induces
◦ Increased heart rate because of increased sympathetic activity to the
heart and decreased parasympathetic activity.
◦ Increased ventricular contractility because of increased sympathetic
activity to the ventricular myocardium.
◦ Arteriolar constriction because of increased sympathetic activity to the
arterioles and increased plasma concentrations of angiotensin II and
vasopressin.
◦ Increased venous constriction because of increased activity to the veins.

119.  The net result is an increased CO (increased heart rate and
stroke volume), increased TPR (arteriolar constriction) and return
of blood pressure toward normal.
 The arterial baroreceptor reflex compensation for decreased
arterial pressure as occurs during a haemorrhage is illustrated in
Fig. 25.
 The compensatory mechanisms do not restore arterial pressure
completely to normal. Toward normal refers to the values before
haemorrhage. For simplicity, reflex increases in angiotensin II
and vasopressin which help to constrict arterioles are not shown.

121.  The major factor for long-term regulation of MAP is blood
volume. This is because it influences venous in turn venous
pressure, venous return, end-diastolic volume, stroke volume and
cardiac output. Thus factors controlling blood volume play a
dominant role in determining blood pressure.
 An increased blood volume increases arterial pressure but this
increased arterial pressure reduces blood volume (particularly the
plasma component of the blood) by increasing the excretion of
salt and water by the kidneys.

122.  Fig. 26 illustrates how the two causal chains constitute
negative-feedback loops that determine both blood volume
and arterial pressure.
◦ An increase in blood pressure causes a decrease in blood volume
which tends to bring the blood pressure back down.
◦ An increase in blood volume raises the blood pressure which tends to
bring the blood volume back down.
 Because arterial pressure and blood volume influence each
other, blood pressure can stabilize in the long run only at a
value at which blood volume is also stable. Thus steady
state blood-volume changes are the single most long-term
determinant of blood pressure.

123. Increase in arterial pressure induces a
decrease in blood volume
Increase in blood volume induces an increase
in arterial pressure

124.  Low blood volume in a haemorrhage produces hypotension (low blood
pressure) .
 Blood loss leads to decreased blood volume, venous pressure, venous
return, arterial pressure and ventricular end-diastolic pressure. These
decrease the stroke volume in the cardiac muscle which hence
decreases cardiac output and the arterial blood pressure
 The most serious consequences of hypotension are reduced blood flow
to the brain and cardiac muscle.

125.  The immediate counteracting response to haemorrhage is the arterial
baroreceptor reflex. Fig. 26 shows how five variables change over time when
there is a decrease in blood volume. It illustrates five simultaneous graphs
showing the time course of the cardiovascular effects of haemorrhage.
 It is important to note that the entire decrease in arterial pressure immediately
following haemorrhage is secondary to the decrease in stroke volume and
hence the CO. All variables shown are increased relative to the state
immediately following the haemorrhage, but not necessarily to the state prior
to the haemorrhage.

127.  The values of the factors changed as a direct result of haemorrhage
(stroke volume, CO and MAP) are restored by the baroreceptor reflex
toward but not to normal.
 In contrast values not altered directly by haemorrhage but only by the
reflex response to haemorrhage (heart rate and TPR) are increased
above their prehaemorrhage values.
 Increases peripheral resistance results from increases in sympathetic
outflow to the arterioles in many vascular beds but not those of the heart
and brain. Thus skin kidney and intestinal blood flow may decrease
markedly.

128.  A second type of compensatory mechanism involves the
movement of interstitial fluid into capillaries.
 The drop in blood pressure and increase in arteriolar constriction
decrease capillary hydrostatic pressure, thereby favouring
absorption of interstitial fluids.
 Thus the initial blood loss and the decreased blood volume is in
large part compensated for by the movement of interstitial fluid
into the vascular system. Fig. 27 illustrates this mechanism.

130.  Approximately 12 to 24 hours after a moderate haemorrhage the
blood volume may be restored virtually to normal by this mechanism.
 At this time the entire restoration of the blood volume is due to
expansion of the plasma volume. This is shown in Table 1.
 Both of these early compensation mechanisms for haemorrhage (the
baroreceptor reflexes and the interstitial fluid absorption) are highly
efficient so that losses of as much as 1.5L of blood approximately
30% of the blood volume can be sustained with only slight reductions
in MAP and CO.

132.  Absorption of interstitial fluid only redistributes the extracellular
fluid. Ultimate replacement of fluid loss involves the control of
fluid ingestion and kidney function.
 Replacement of lost erythrocytes requires the stimulation of
erythropoiesis by erythropoietin. This replacement requires days
to weeks in contrast to the rapidly occurring reflex
compensations described.

133.  “Shock” denotes any situation in which a decrease in blood flow to the
organs and tissues damages them.
 Decrease in blood volume secondary to haemorrhage or loss of fluid
other than blood can result in a type of shock called hypovolemic
shock.
 The heart suffers damage if shock is prolonged. As it deteriorates, CO
declines markedly and shock becomes progressively worse and
ultimately irreversible even if blood pressure is temporarily restored.

135.  Hypotension and hypertension as it relates to the
cardiovascular system.
 Understand the upright posture.
 Discuss the role of exercise in cardiovascular system.
 Discuss what causes heart failure.
 Explain coronary artery disease and heart attack.
 Explain drugs used in hypertension / heart failure
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136. The heart pumps blood into the arteries which goes throughout the
body and cells.
When the heart muscles contract, blood is forced out.
 The contraction is as a result of the heart beating and the pressure
building up.
 This is the systolic blood pressure.
 The relaxation between beats is the diastolic pressure.

137.  Blood pressure is measured in millimeters of Mercury (mm Hg)
 Systolic pressure is when the heart contracts while diastolic pressure
is when it relaxes.
 Normal Blood Pressure:
120 140
80 90
HIGH =

139.  Loss of Blood volume e.g.. hemorrhage. Erythrocytes needs hormone
erythropoietin to stimulate erythropoiesis.
CAUSES
 Reduced blood flow in brain and cardiac muscle.
 Loss of salt which causes a loss of water e.g.. diarrhea, vomiting.
 Strong emotions e.g.. fainting.
 Shock (may be reversible by blood transfusion and therapy).

140. THREE TYPES Of SHOCK
 Hypovolemic – decreased blood volume.
 Low Resistance – decreased in total peripheral resistance.
 Cardiogenic – decrease in cardiac output.

141.  Peripheral resistance: the resistance to pump blood in the
small arterial branches that carry blood to tissues.
 Cardiac output: the volume of blood pumped by heart within a
specified time.

142.  Bleeding or abnormal flow of blood.
 Transfusion helps in restoring blood volume.
 Interstitial fluid goes into the capillaries causing the blood pressure to
drop.
 Increased arteriolar constriction decreases capillary hydrostatic
pressure and interstitial fluid is absorbed.

144.  This is movement from a horizontal/lying position to a
vertical/standing one. The blood vessels are in the same level with the
heart.
 Gravity increases the pressure of the body below the heart and
decreases the pressure force in organs above the heart.
 Increase in capillary pressure caused by gravity, increases filtration of
fluid out of capillaries. This causes swelling of feet after a long period
of standing.

145.  This involves blood vessels of the heart.
 A major contributor to this disease is a build up of
plaque in vessels which slows down blood flow.

146.  Can be noticed from both increase of cardiac output and peripheral
resistance.
 Increased peripheral resistance caused by reduced arteriolar radius.
 Hypertension of unknown cause is called primary hypertension.
 Caused by excessive sodium as a contributing factor.
 Caused by increased release of renin from the kidney.

147.  The cardiac output is low. This is caused by elevated arterial
pressure due to hypertension.
 Heart failure has two groups: diastolic dysfunction and systolic
dysfunction.
 These two groups trigger arterial baroreceptors reflexes. This leads to
pulmonary edema.
 Increased total peripheral resistance.
 Symphatic nerves to arterioles.
 Angiotensin 11 and vasopressin.

149.  Smoking - Homocysteine
 Cholesterol - Hypertension
 Diabetes - Obesity
 Stress

150.  Nutrition – decrease intake of saturated fats.
 Supplements – folic acid reduces blood concentration of amino acid
(HOMOCYSTEINE).
 Alcohol – red wine in moderation has the power to help reduce rush
of heart attack.
 Metabolized methionine and cysteine which is in high amounts has
pro atherosclerosis effects.

151.  Decreased myocardial oxygen demand.
 Increase coronary arteries diameter.
 Decrease effect of hypertension and obesity.
 Decrease total plasma concentration.
 Decrease of blood clot and improving the ability to dissolve them.

153.  Changes in coronary artery cause insufficient blood flow (ischemia)
and myocardial damage can exist.
 Myocardial infraction/heart attack – inadequate coronary blood flow
in exertion or emotional tension.
 Symptoms – prolonged chest pain (more persistent in left arm)-
nausea, vomiting, sweating, weakness, shortness of breath
 This can be diagnosed by an ECG which measures certain protein in
plasma that leak into the blood when muscle is damaged.

154.  Sudden cardiac death during myocardial infraction is due to
ventricular fibrillation where myocardial cells are damaged and causes
abnormal conductive when the ventricular contraction are
uncoordinated.
 Only a small amount of people can be saved by CPR.
 Cardiopulmonary resuscitation- allows small amounts of oxygenated
blood to vital organs after which a more precise treatment is used.
Electric current pass through heart to stop the abnormal electrical
activity.
 Artificial fibrillation causes minor cardiac problems.

155. ARTHEROSCLEROSIS
 Caused by plaque.
 Cells lining the blood vessels get damaged from high LDL
cholesterol
 eg. Smoking high levels.
 increase penetrability of blood vessel walls.
 achieve inflammatory response.
 Immune System sends macrophages.
 Smooth muscle cells in artery try to repair damage.

156. ARTHEROSCLEROSIS
 LDL particles trapped in blood vessel walls.
 Free radicals oxidize LDL cholesterol.
 Macrophages engulf oxidize LDL and swell forming plaque..
 Statins interferes with an enzyme involve in liver synthesis
of Cholesterol which helps control atherosclerosis.

158. CORONARY THROMBOSIS
 Blood Clot.
 Try reducing clotting with Aspirin®
 Statins drug interfere with a critical enzyme involved in liver
synthesis of cholesterol.

159.  ACE inhibitors, prevents the angiotensin converting enzyme ACE which
is an enzyme that converts angiotensin1 to angiotensin 11. This lowers
blood pressure by dilating arteries.
 Types of drugs:
 Enalapril
 Lisinopril
 ramipril

160.  This helps kidney eliminate excess salt and water from body tissues and
blood.
 Drugs: bumetamide, furosemide, microzide, acetazalamide diamox

161.  Reduces cardiac output it slows heart rate reducing stress on heart and
arteries. This prevents the effect of adrenaline.
 Drugs: lopressor, blocadren,normodye, carteolol

162.  Reduce calcium in smooth muscle cells.
 Lower peripheral resistance.
 Blood pressure is reduced by the dilation of arteries.
 Drugs: amlodipine(norvasc), feladipine, nifedipine
(adalat)

163.  This also dilate arteries.
 Drugs: candesartar, losartan, valsartan.

164.  Diuretics.
 Cardiac inotropic drugs ( digitalis)
 This makes heart beat stronger.
 Dobutamine helps to use norepinephrine.
 Dopamine increase amount of norepinephrine in body.
 Aspirin (acetyl salicylic acid ASA).This prevents platelets in blood from
clotting which is forms in atherosclerosis.

165.  Lowers peripheral blood resistance whereby heart work less to pump
blood.
 ACE inhibitor are used as vasodilators.
CALCIUM CHANNEL BLOCKERS:
 used in heart failure, if it is due to high blood pressure. It is used if patient
is not responding to ACE or ARB inhibitors.

166.  Blocks the action of norepinephrine on heart muscles improving systolic
function of the left ventricle.
 Influence the RAS system in kidney.
 Drugs: celiprotol, sotalol, labetalol