These notes are intended to accompany lectures in Human Physiology by Dr. Peter King at Francis Marion University, Florence, SC 29501.
Why don't we have cells as big as elephants?
Surface area to volume ratio decreases with size.
This limits transport of nutrients and wastes.Multicellular organisms
like humans have a problem getting materials to and from cells.
Many invertebrates have open circulatory systems where some
important organs are bathed in blood and diffusion from other
tissue allows exchange of nutrients and wastes.
All vertebrates have closed cardiovascular systems that move blood
in an orderly and controlled manner around the body.
Although it is called a closed system in fact it is not completely
closed. Fluid continually is lost from capillaries and enters
the interstitial space between cells, carrying nutrients.
This fluid is returned to the cardiovascular system by the lymph
system.
A closed system are more efficient as it allows greater exchange
rates because of the constant flow of blood.
The vertebrate body is approximately 70% water.
This is distributed in the body in three major categories
Intracellular water 45%
Interstitial water 20%
Plasma 5%
Cardiovascular system is responsible (together with the lymphatic
system) for moving the water and maintaining homeostasis of the
interstitial fluid that baths the cells.
Cells are constantly exchanging ions, gases, nitrogenous waste,
amino acids sugars etc. with the interstitial fluid in order to
maintain there own internal environments.
Added to the distribution of solutes is the distribution of heat.
Blood is the fluid that is pumped throughout the cardiovascular
system.
It is strictly classified as a connective tissue and has special
cells and a matrix. Unlike other connective tissues the matrix
is fluid and the fibrous proteins are dissolved
The specialized cells are the formed elements and the matrix is
the plasma.
The formed elements are:
erythrocytes
leukocytes
platelets
Plasma makes up the balance about 55% of the approx. 5.5 liters of blood in
a human.
The formed elements are easily separated by centifusion.
This is a common test to produce an individuals hematocrit - a rough
test of erythrocyte volume.
Normal hematocrits range from 42-52 in males and 37-47 in females.
Plasma
Plasma is a light yellow fluid, water and dissolved solutes.
Solutes include ions (Na+, K+ etc.), dissolved gases,
and organic molecules such as, glucose, aminoacids, hormones, enzymes and plasma
proteins.
Plasma proteins make up about 8% of plasma (by weight).
Three main types
albumins
globulins
fibrinogen
Plasma proteins make up about 8% of plasma
Albumins - most abundant (60% of proteins), produced in the liver to
maintain osmotic balance between blood and tissue.
Globulins - (36% of proteins) alpha, beta and gamma
alpha and beta; produced in liver, transport proteins,
lipids and lipid soluble vitamins
gamma; released by B lymphocytes and plasma cells, antibodies
Fibrinogen - produced in liver, converted to fibrin (insoluble) to form
blood clot.
Other - enzymes, hormones etc
Plasma reflects the water balance of the body. Dehydartion results in an increased osmolarity of plasma which stimulates water retention.
Formed elements - blood cells and platelets produced in bone
marrow from hemocytoblasts.
Erythrocytes are red blood cells. Biconcave cells, about 7mm
diameter, no nucleus, no mitochondria or other normal organelles. There are
about 5,000,000 in each ml of blood. They last about 120 days. Each second about
2.5 million new erythrocytes are produced or about 200 billion each day.
Each cell contains about 280,000,000 molecules of hemoglobin. Hemoglobin binds
oxygen increasing the amount dissolved in blood.
Leukocytes are nucleated and have mitochondria. Have the ability to leave the bloodstream (diapedesis). Almost invisible they are named after histological stains. They are grouped as granular or agranular
Granular leukocytes - all phagocytes
Eosinophils, granules stain with eosin (pink). 1-4% of leukocytes.
Granules are lysosomes full of unique digestive enzymes. Defense
against parasitic worms. Also phagocytize foreign proteins and
immune complexes.
Basophils, granules stain with a blue basic stain. Rarest
of leucocytes. Granules contain histamine, an inflammatory
chemical that act as a vasodilator, increases capillary permeability,
and attracts other leukocytes. Mast cells in other connective
tissue almost identical.
Neutrophils are the most common leukocytes and granules
take up eosin and basic blue to create a lilac color. Granules
contain digestive enzymes (lysosomes) and antibiotic proteins.
Attracted to sites of inflammation, particularly to phagocytize
bacteria (and some fungi).Numbers increase greatly during
acute bacterial infections.
Agranular leukocytes
Monocytes, largest of the leukocytes. Move to the tissue and differentiate
into very mobile macrophages (large active phagocytes). Increase greatly
during infections, particuarly viral and intracellular bacterial infections.
Activate lymphocytes.
Lymphocytes, second most numerous lymphocyte. Not many in blood, most
migrate to lymph nodes and spleen.
T-lymphocytes act directly against virus infected cells and tumors.
B-lymphocytes produce plasma cells which produce antibodies (immunoglobulins)
Platelets
Platelets are not cells, but cytoplasmic fragments of large cells called megakarycytes.
Lack a nucleus but can move through tissue.Have an important role in blood clotting.
Hematopoiesis
All blood cells form from cells that originate in the yolk sac of the embryo,
migrate to the embryonic liver and then to the bone marrow after birth.
Formation of erythrocytes, erythropoiesis, is very active. 2.5 million
erythrocytes produced every second in adults. The hormone (a cytokine) Erythropoietin
is secreted by the kidneys in response to low oxygen levels in blood,
it binds to hemocytoblasts, causing them to differentiate into erythroblasts.
Developing erythrocytes produce hemoglobin. Maturation takes about 3 days and
cells live about 120 days. Old erythrocytes destroyed by macrophages in the
spleen. Hemoglobin is converted to bilirubin which is filtered in the liver
and excreted in bile.
Formation of leukocytes stimulated by a variety of cytokines (colony-stimulating
factors and interleukins).
Bone marrow transplants important in the treatment of many blood
disorders because it replaces stem cells, hemocytoblasts.
Blood types
Blood is commonly typed using the ABO system. This is caused
by erythrocyte membrane antigens. Antigens are present
on all cells and are used by the bodies immune system to recognize
self. Antibodies recognize antibodies of nonself.
It becomes important in blood cells because of the prevalence
of blood transfusions (and fortuneately it is a simple system).
There are only 2 antigens in this ABO system.
Type A blood has antigen AType B blood has antigen BType AB
blood has antigens A and BType O blood has no A or B antigens
A problem arises because of antibodies.
Type A blood has antibody B (anti B)
Type B blood has anti A
Type AB blood has no anti A or anti B
Type O blood has anti A and anti B
Antibodies binding to antigens cause clumping of erythrocytes
or agglutination.
ABO system caused by one gene position with three alleles,
IA, IB and i, with IA and IB being co-dominant and i being recessive.
What blood type would an individual be with a genotype of IA,
i?
type A
Genotype IA, IB ?
type AB
Genotype i,i?
type O
Back to the cardiovascular system
Our circulation is divided into a pulmonary circulation
(to the lungs) and a systemic circulation (to the body).
These have separate functions i.e the pulmonary circulation allows
blood to be oxygenated and dump carbon dioxide, the systematic
circulation distributes blood to the body.
Blood is pumped through these systems by the heart.
So how does the heart work?
The human heart is basically two pumps with two inlets and two
outlets.
Blood is expelled when cardiac muscle contracts and the volume
inside the chambers decreases.
Blood flow is directed by pressure variances and a series of valves (tricuspid,
bicuspid and 2 semilunar valves) which prevent backflow.
A heartbeat consists of a rhythmical contraction (systole)
of the cardiac muscle followed by relaxation (diastole).
Contraction is initiated at the sinoatrial node.
The sinoatrial (SA) node is the pacemaker. It consists
of specialized muscle fibers that have 'leaky' membranes and undergo
regular depolarization, i.e. after a refractory period Na+ enters
the cell depolarizing it toward threshold (spontaneous depolarization).
Action potentials in the SA node spread to other cells via
gap junctions. The AP spreads across both atria at a rate
of 0.8-1.0 m/s.
Atria are insulated from the ventricles and the AP does not travel
unimpeded across the entire heart.
The atrial AP stimulates cells in the atrioventrical (AV) node.
These are specialized muscle cells that conduct the AP slowly
(0.03 - 0.1m/s) to the ventricle.
This slow down of conduction is important in allowing
blood time to fill the ventricles.
The atrioventricle (AV) node cells conduct the AP to other faster
conducting cells, the bundle of His, right and left bundle
branches and finally to the Purkinje fibers (5m/s).
Ventricular contraction begins about 0.1 - 0.2 seconds after contraction
of the atria.
Purkinje fibers stimulate cardiac muscle and a wave of
contraction sweeps across the ventricle from the apex.
An action potential in a cardiac fiber is slightly different from skeletal muscle. Rapid inflow of Na+ is followed by a more sustained inflow of Ca++, which sustains depolarization and extends the refractory period. Eventually K+ channels open and the cell is repolarized. A cardiac muscle twitch will last in the order of 0.3 seconds.
Electrical activity can be recorded on an electrocardiogram
(ECG or EKG). The water in our body make it a good conductor
of electricity and the depolarization events of the heart can
be measured on the skin surface.
A cardiac cycle produces 3 distinct ECG waves, P, QRS and T.
The P wave represents the spread of atrial depolarization.
QRS wave represents ventricular depolarization.
T wave represents ventricular repolarization
The base heart rate is determined by the pacemaker cells in
the SA node. The SA node is influenced by the autonomic nervous
system.
Parasympathetic stimulation via the vagus nerve (ACh) decreases
heart rate.
ACh increases K+ leakage in the pacemaker cells
and it therefore takes longer to depolarize to the threshold level.
Norepinephrine from the sympathetic nervous system increases
Na+ and Ca++ conductance and possibly
reduces K+ outflow during repolarization and increases
heart rate.
Epinephrine from the adrenal gland will also have this effect.
Cardiac output is a combination of heart rate and stroke
volume.
Heart rate is controlled by autonomic input.
Stroke volume is controlled by 3 factors
1. end diastolic volume - determined by pressure in the
veins and atrial contraction.
2. total peripheral resistance
3. force of contraction - autonomic control - norepinephrine
increases force of contraction, and stretch.
The Frank-Starling law of the heart describes the intrinsic property of the heart that as end diastolic volume increases, the cardiac muscle is stretched and within normal limits becomes more efficient (remember length of muscle and force of contraction) and force increases to expel contents.
After the blood leaves the heart it enters arteries.
The elastic walls of arteries absorb some of the pressure from
ventricular contraction and keep the blood flowing during diastole.
Small arteries or arterioles are the site of greatest resistance
to blood flow.
Contraction of circular smooth muscle in arterioles is a major
control mechanism for blood flow control. There are also circular
sphincters in some capillaries.
Capillaries are exchange sites for blood vessels. Combined
cross-sectional area of all capillaries is much larger than other
blood vessels and blood velocity is correspondingly low.
Capillary diameter is only just big enough to allow passage of
red blood cells.
Endothelial cells are very thin to facilitate diffusion.
Capillaries often have pores or fenestra to increase allow
secretion of plasma.
Solutes with small molecular weight diffuse from the blood.
Most proteins are held in capillaries.
Some fluid forced through endothelium (semipermeable membrane)
by blood hydraulic pressure.
Colloidal osmotic pressure caused by proteins in blood increases
as fluid is lost until equilibrium achieved.
Plasma proteins essential to retain fluid in blood.
Are capillaries always filled with blood?
No, capillaries are not always filled with blood.
e.g. Blood flow to skin very variable and used for thermoregulation.Blood
flow to muscle can increase by 30x during exercise in human athlete.
Secretion of plasma with its accompanying dissolved nutrients
is important for our cells.There is 4 times the amount of fluid
in the interstitial fluid than in out blood vessels.
i.e. 3-3.5 L in plasma, 11-13L in interstitial fluid.
Each of our cells needs the homeostatic balance of the interstitial
fluid to provide a healthy environment.
The interstitial fluid is drained by the lymphatic system.
Everywhere there are capillaries there are lymph vessels.
Lymph nodes are expanded areas of lymph vessels that
contain many phagocytes and lymphocytes.
Lymph vessels drain back into the subclavian veins and the fluid
rejoins the cardiovascular system.
The cardiovascular system is not entirely closed and part of the
fluid in our bodies is circulating from blood to tissue and back
to the blood.
Blood leaving the capillary beds enter venules and then veins.
Blood pressure is very low in veins and blood tends to gather
here. About 60-70% of blood is in the veins and it is somewhat
of a reservoir that can be mobilized by contraction of these blood
vessels
Valves are present to prevent backflow and skeletal
muscle contraction is important to move the blood.
Control of blood flow
Overall blood pressure is maintained within normal limits (homeostasis) by a
negative feedback system. Mean arterial pressure (MAP) in the systemic system
is 90 mm Hg ranging from about 120 mm Hg during systole and 80 mm Hg during
diastole (BP 120/80). MAP in the pulmonary system is only 15 mm Hg.
Baroreceptors (actually stretch receptors) are located in the aortic
arch and the carotid arteries. These are connected to the the medulla oblongata.
The vasomotor control center and the cardiac control center alter stroke rate
and stroke volume and peripheral resistance to maintain pressure.
Changes in peripheral resistance directs blood to various organs.
Other intrinsic controls allow increased blood flow to an organ as metabolism
increases. Lack of oxygen, build up of carbon dioxide, decreased pH for example
all promote vasodilation.
Extrinsic control is control by the autonomic nervous system. This can
work in conjunction with intrinsic controls. During exercise intrinsic controls
cause vasodilation in skeletal muscle. Sympathetic stimulation reinforce this
response and redirect blood by constricting vessels to the GI tract.
Increased oxygen demand
During activity the increased oxygen demand is met in part by increased
cardiac output. This can be achieved by increased stroke volume and/or increased
heart rate.
Cardiac output does not increase in proportion to oxygen consumption.
Balance of oxygen demand supplied by greater extraction of oxygen from blood.
Average human increase oxygen consumption by about 12x during hard exercise. Heart rate increases 2.5x, stroke volume increases about 1.5x, oxygen extraction increases by 3x.
Circulation to the skin can be controled by normal arteriole
constriction but a second mechanism exists.
Arteriovenous anastomoses (connections) can be opened to bypass
dermal capillaries. This mechanism is extremely important for
control of body heat.
Normal blood pressure is an important feature of health as
it ensures proper distribution of blood and along with it nutrients
for all our cells.
Heart function is an integral part of distributing the blood and
heart malfunction is the leading cause of death in humans.
Clinical question
Why is edema a result of heart failure?
A number of drug types are prescribed for high blood pressure including beta blockers, calcium channel blockers and ACE inhibitors. How do they work?
This webpage was created by Peter King. Please contact the
the author with comments at pking@fmarion.edu.
Last edited July 20, 2010.
http://people.fmarion.edu/pking/humanphys/cardiovas.html
copyright Peter King.