THE BLOOD
Functions of Blood
Blood has three general functions:
1. Transportation. blood transports oxygen from the lungs to the cells of the body and
carbon dioxide from the body cells to the lungs for exhalation. It carries nutrients
from the gastrointestinal tract to body cells and hormones from endocrine glands to
other body cells. Blood also transports heat and waste products to various organs for
elimination from the body.
2. Regulation. Circulating blood helps maintain homeostasis of all body fluids. Blood
helps regulate pH through the use of buffers (chemicals that convert strong acids or
bases into weak ones).
3. Protection. Blood can clot (become gel-like), which protects against its excessive
loss from the cardiovascular system after an injury. In addition, its white blood cells
protect against disease by carrying on phagocytosis. Several types of blood proteins,
including antibodies, interferons, and complement, help protect against disease in a
variety of ways.
Physical Characteristics of Blood
The temperature of blood is 38°C about 1°C higher than oral or rectal body
temperature, and it has a slightly alkaline pH ranging from 7.35 to 7.45. The color of
blood varies with its oxygen content. When saturated with oxygen, it is bright red.
When unsaturated with oxygen, it is dark red. Blood constitutes about 20% of
extracellular fluid, amounting to 8% of the total body mass. In human the blood
volume is 5 to 6 liters in an average-sized adult male and 4 to 5 liters in an averagesized adult female.
Components of Blood
Whole blood has two components: (1) blood plasma, and (2) formed elements,
which are cells and cell fragments. Blood is about 45% formed elements and 55%
blood plasma. Normally, more than 99% of the formed elements are red blood cells
(RBCs). Pale, colorless white blood cells (WBCs) and platelets occupy less than 1%
of the formed elements.
Blood Plasma
When the formed elements are removed from blood, a straw-colored liquid called
blood plasma (or simply plasma) is left. Blood plasma is about 91.5% water and
8.5% solutes, most of which (7% by weight) are proteins. called plasma proteins.
Hepatocytes (liver cells) synthesize most of the plasma proteins, which include the
albumins (54% of plasma proteins), globulins (38%), and fibrinogen (7%). Certain
blood cells develop into cells that produce gamma globulins, an important type of
globulin. These plasma proteins are also called antibodies or immunoglobulins
because they are produced during certain immune responses. Foreign substances
(antigens) such as bacteria and viruses stimulate production of millions of different
antibodies. An antibody binds specifically to the antigen that stimulated its production
and thus disables the invading antigen. Besides proteins, other solutes in plasma
include electrolytes, nutrients, regulatory substances such as enzymes and hormones,
gases, and waste products such as urea, uric acid, creatinine, ammonia, and bilirubin.
Formed Elements
The formed elements of the blood include three principal components:
red blood cells (RBCs), white blood cells (WBCs), and platelets. RBCs and WBCs
are whole cells; platelets are cell fragments. Several distinct types of WBCs—
neutrophils, lymphocytes, monocytes, eosinophils, and basophils—each with a
unique microscopic appearance, carry out these functions. Following is the
classification of the formed elements in blood:
I. Red blood cells
II. White blood cells
A. Granular leukocytes (contain conspicuous granules that are visible under a light
microscope after staining)
1. Neutrophils
2. Eosinophils
3. Basophils
B. Agranular leukocytes (no granules are visible under a light microscope after
staining)
1. T and B lymphocytes and natural killer (NK) cells
2. Monocytes
III. Platelets
The percentage of total blood volume occupied by RBCs is called the hematocrit, a
hematocrit of 40 indicates that 40% of the volume of blood is composed of RBCs.
The normal range of hematocrit for adult females is 38–46% (average 42%); for adult
males, it is 40–54% (average 47%).
FORMATION OF BLOOD CELLS
called hemopoiesis or hematopoiesis. Red bone marrow becomes the primary site of
hemopoiesis in the last 3 months before birth, and continues as the source of blood
cells after birth and throughout life.
RED BLOOD CELLS
Red blood cells (RBCs) or erythrocytes contain the oxygen-carrying protein
hemoglobin, which is a pigment that gives whole blood its red color. In human a
healthy adult male has about 5.4 million red blood cells per microliter (µL) of blood,
and a healthy adult female has about 4.8 million. RBCs are biconcave discs with a
diameter of 7–8µm.
RBC Physiology
Each RBC contains about 280 million hemoglobin molecules. A hemoglobin
molecule consists of a protein called goblin, composed of four polypeptide chains
(two alpha and two beta chains); a ring like nonprotein pigment called a heme is
bound to each of the four chains. At the center of each heme ring is an iron ion
(Fe2+) that can combine reversibly with one oxygen molecule, allowing each
hemoglobin molecule to bind four oxygen molecules. Each oxygen molecule picked
up from the lungs is bound to an iron ion. As blood flows through tissue capillaries,
the iron–oxygen reaction reverses. Hemoglobin releases oxygen, which diffuses first
into the interstitial fluid and then into cells. Hemoglobin also transports about 23% of
the total carbon dioxide, a waste product of metabolism. (The remaining carbon
dioxide is dissolved in plasma or carried as bicarbonate ions.)
Blood flowing through tissue capillaries picks up carbon dioxide, some of which
combines with amino acids in the globin part of hemoglobin. As blood flows through
the lungs, the carbon dioxide is released from hemoglobin and then exhaled.
WHITE BLOOD CELLS
Functions of WBCs
In a healthy body, some WBCs, especially lymphocytes, can live for several months
or years, but most live only a few days. During a period of infection, phagocytic
WBCs may live only a few hours. WBCs are far less numerous than red blood cells;
at about 5000–10,000 cells per microliter of blood, they are outnumbered by RBCs by
about 700:1. Leukocytosis, an increase in the number of WBCs above 10,000/µL, is a
normal, protective response to stresses such as invading microbes, strenuous exercise,
anesthesia, and surgery. An abnormally low level of white blood cells (below
5000/µL) is termed leukopenia.
Once pathogens enter the body, the general function of white blood cells is to combat
them by phagocytosis or immune responses.
To accomplish these tasks, many WBCs leave the bloodstream and collect at sites of
pathogen invasion or inflammation. Once granular leukocytes and monocytes
leave the bloodstream to fight injury or infection, they never return to it.
Lymphocytes, on the other hand, continually recirculate — from blood to interstitial
spaces of tissues to lymphatic fluid and back to blood. Only 2% of the total
lymphocyte population is circulating in the blood at any given time; the rest is in
lymphatic fluid and organs such as the skin, lungs, lymph nodes, and spleen.
WBCs leave the bloodstream by a process termed emigration also called diapedesis,
in which they roll along the endothelium, stick to it, and then squeeze between
endothelial cells.
Neutrophils and macrophages are active in phagocytosis, they can ingest bacteria
and dispose of dead matter. Several different chemicals released by microbes and
inflamed tissues attract phagocytes, a phenomenon called chemotaxis.
Eosinophils leave the capillaries and enter tissue fluid. They are believed to release
enzymes, such as histaminase, that combat the effects of histamine and other
substances involved in inflammation during allergic reactions. Eosinophils also
phagocytize antigen–antibody complexes and are effective against certain parasitic
worms. A high eosinophil count often indicates an allergic condition or a parasitic
infection. At sites of inflammation, basophils leave capillaries, enter tissues,
and release granules that contain heparin, histamine, and serotonin. These
substances intensify the inflammatory reaction and are involved in hypersensitivity
(allergic) reactions
Basophils are similar in function to mast cells, connective tissue cells that originate
from pluripotent stem cells in red bone marrow. Like basophils, mast cells release
substances involved in inflammation, including heparin, histamine, and proteases.
Mast cells are widely dispersed in the body, particularly in connective tissues of the
skin and mucous membranes of the respiratory and gastrointestinal tracts.
Lymphocytes are the major soldiers in immune system battles. Most lymphocytes
continually move among lymphoid tissues, lymph, and blood, spending only a
few hours at a time in blood. Three main types of lymphocytes are B cells, T cells,
and natural killer (NK) cells. B cells are particularly effective in destroying bacteria
and inactivating their toxins. T cells attack viruses, fungi, transplanted cells, cancer
cells, and some bacteria, and are responsible for transfusion reactions, allergies, and
the rejection of transplanted organs. Immune responses carried out by both B cells and
T cells help combat infection and provide protection against some diseases.
Natural killer cells attack a wide variety of infectious microbes and certain
spontaneously arising tumor cells.
Monocytes take longer to reach a site of infection than neutrophils, but they arrive in
larger numbers and destroy more microbes. On their arrival, monocytes enlarge and
differentiate into wandering macrophages, which clean up cellular debris and
microbes by phagocytosis after an infection. As you have already learned, an increase
in the number of circulating WBCs usually indicates inflammation or infection.
PLATELETS
Between 150,000 and 400,000 platelets are present in each microliter of blood. Each
is irregularly disc-shaped, 2–4µm in diameter, and has many vesicles but no nucleus.
Their granules contain chemicals that, once released, promote blood clotting. Platelets
help stop blood loss from damaged blood vessels by forming a platelet plug. Platelets
have a short life span, normally just 5 to 9 days. Aged and dead platelets are removed
by fixed macrophages in the spleen and liver.
HEMOSTASIS
Hemostasis,
is a sequence of responses that stops bleeding. Three mechanisms reduce blood loss:
(1) vascular spasm, (2) platelet plug formation, and (3) blood clotting (coagulation).
Vascular Spasm
When arteries or arterioles are damaged, the circularly arranged smooth muscle in
their walls contracts immediately, a reaction called vascular spasm. This reduces
blood loss for several minutes to several hours, during which time the other
hemostatic mechanisms go into operation.
Platelet Plug Formation
Considering their small size, platelets store an impressive array of chemicals. Within
many vesicles are clotting factors, ADP, ATP, Ca2+, and serotonin. Also present are
enzymes that produce thromboxane A2, a prostaglandin; fibrin-stabilizing factor,
which helps to strengthen a blood clot; lysosomes; some mitochondria; membrane
systems that take up and store calcium and provide channels for release of the
contents of granules; and glycogen.
Platelet plug formation occurs as follows:
●1 Initially, platelets contact and stick to parts of a damaged blood vessel, such as
collagen fibers of the connective tissue underlying the damaged endothelial cells. This
process is called platelet adhesion.
●2 Due to adhesion, the platelets become activated, and extend many projections that
enable them to contact and interact with one another.
.●3 They release ADP so become sticky, and the stickiness recruits and activates
other platelets to adhere to the originally activated platelets. This gathering of
platelets is called platelet aggregation.
Eventually, the accumulation and attachment of large numbers of platelets form a
mass called a platelet plug.
Blood Clotting
The process clotting or coagulation, is a series of chemical reactions that culminates
in formation of fibrin threads. Thrombosis—clotting in an undamaged blood vessel.
Clotting involves several substances known as clotting (coagulation) factors. These
factors include calcium ions (Ca2+), several inactive enzymes that are synthesized by
hepatocytes (liver cells) and released into the bloodstream, and various molecules
associated with platelets or released by damaged tissues.
Clotting can be divided into three stages;
●1 Two pathways, called the extrinsic pathway and the intrinsic pathway, lead to
the formation of prothrombinase. Once prothrombinase is formed, the steps involved
in the next two stages of clotting are the same for both the extrinsic and intrinsic
pathways, and together these two stages are referred to as the common pathway.
●2 Prothrombinase converts prothrombin (a plasma protein formed by the liver) into
the enzyme thrombin.
●3 Thrombin converts soluble fibrinogen (another plasma protein formed by the
liver) into insoluble fibrin. Fibrin forms the threads of the clot.
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The Extrinsic Pathway
The extrinsic pathway of blood clotting is so named because a tissue protein called
tissue factor (TF), also known as thromboplastin, leaks into the blood from cells
outside (extrinsic to) blood vessels and initiates the formation of prothrombinase. In
the presence of Ca2+, TF begins a sequence of reactions that ultimately activates
clotting factor X. Once factor X is activated, it combines with factor V in the
presence of Ca2+ to form the active enzyme prothrombinase, completing the extrinsic
pathway.
The Intrinsic Pathway
The intrinsic pathway of blood clotting is so named because its activators are either
in direct contact with blood or contained within (intrinsic to) the blood; outside tissue
damage is not needed. If endothelial cells become roughened or damaged, blood can
come in contact with collagen fibers in the connective tissue around the endothelium
of the blood vessel. In addition, trauma to endothelial cells causes damage to platelets,
resulting in the release of phospholipids by the platelets. Contact with collagen fibers
(or with the glass sides of a blood collection tube) activates clotting factor XII which
begins a sequence of reactions that eventually activates clotting factor X. Platelet
phospholipids and Ca2+ can also participate in the activation of factor X. Once factor
X is activated, it combines with factor V to form the active enzyme prothrombinase
(just as occurs in the extrinsic pathway), completing the intrinsic pathway.
The Common Pathway
The formation of prothrombinase marks the beginning of the common pathway. In the
second stage of blood clotting, prothrombinase and Ca2_ catalyze the conversion of
prothrombin to thrombin. In the third stage, thrombin, in the presence of Ca2_,
converts fibrinogen, which is soluble, to loose fibrin threads, which are insoluble.
Thrombin also activates factor XIII (fibrin stabilizing factor), which strengthens and
stabilizes the fibrin threads into a sturdy clot. Plasma contains some factor XIII,
which is also released by platelets trapped in the clot.
Clot Retraction
Once a clot is formed, it plugs the ruptured area of the blood vessel and thus stops
blood loss. Clot retraction is the consolidation or tightening of the fibrin clot. The
fibrin threads attached to the damaged surfaces of the blood vessel gradually contract
as platelets pull on them.
BLOOD GROUPS AND BLOOD TYPES
The surfaces of erythrocytes contain a genetically determined assortment
of antigens composed of glycoproteins and glycolipids. These antigens, called
agglutinogens occur in characteristic combinations. Based on the presence or absence
of various antigens, blood is categorized into different blood groups.
ABO Blood Group
The ABO blood group is based on two glycolipid antigens called A and B. People
whose RBCs display only antigen A have type A blood. Those who have only antigen
B are type B. Individuals who have both A and B antigens are type AB; those
who have neither antigen A nor B are type O.
Blood plasma usually contains antibodies called agglutinins that react with the A or
B antigens if the two are mixed. These are the anti-A antibody, which reacts with
antigen A, and the anti-B antibody, which reacts with antigen B.
You do not have antibodies that react with the antigens of your own RBCs, but you do
have antibodies for any antigens that your RBCs lack. For example, if your blood type
is B, you have B antigens on your red blood cells, and you have anti-A antibodies in
your blood plasma.
Transfusions
A transfusion is the transfer of whole blood or blood components (red blood cells
only or blood plasma only) into the bloodstream or directly into the red bone marrow.
However, the normal components of one person’s RBC plasma membrane can trigger
damaging antigen–antibody responses in a transfusion recipient. In an incompatible
blood transfusion, antibodies in the recipient’s plasma bind to the antigens on the
donated RBCs, which causes agglutination, or clumping, of the RBCs. Agglutination
is an antigen–antibody response in which RBCs become cross-linked to one another.
When these antigen–antibody complexes form, they activate plasma proteins of the
complement family. In essence, complement molecules make the plasma membrane
of the donated RBCs leaky, causing hemolysis or rupture of the RBCs and the release
of hemoglobin into the blood plasma. The liberated hemoglobin may cause kidney
damage by clogging the filtration membranes.
Consider what happens if a person with type A blood receives a transfusion of type B
blood. The recipient’s blood (type A) contains A antigens on the red blood cells and
anti-B antibodies in the plasma. The donor’s blood (type B) contains B antigens and
anti-A antibodies. In this situation, two things can happen. First, the anti- B antibodies
in the recipient’s plasma can bind to the B antigens on the donor’s erythrocytes,
causing agglutination and hemolysis of the red blood cells. Second, the anti-A
antibodies in the donor’s plasma can bind to the A antigens on the recipient’s red
blood cells, a less serious reaction because the donor’s anti-A antibodies become
so diluted in the recipient’s plasma that they do not cause significant agglutination
and hemolysis of the recipient’s RBCs.
People with type AB blood do not have anti-A or anti-B antibodies in their blood
plasma. They are sometimes called universal recipients because theoretically they can
receive blood from donors of all four blood types. They have no antibodies to attack
antigens on donated RBCs. People with type O blood have neither A nor B antigens
on their RBCs and are sometimes called universal donors because theoretically they
can donate blood to all four ABO blood types. Type O persons requiring blood may
receive only type O blood. In practice, use of the terms universal recipient and
universal donor is misleading and dangerous.
Blood contains antigens and antibodies other than those associated with the ABO
system that can cause transfusion problems. Thus, blood should be carefully crossmatched or screened before transfusion.
Rh Blood Group
The Rh blood group is so named because the Rh antigen, called Rh factor, was first
found in the blood of the Rhesus monkey.
People whose RBCs have Rh antigens are designated Rh+ (Rh positive); those
who lack Rh antigens are designated Rh- (Rh negative).
Normally, blood plasma does not contain anti-Rh antibodies. If an Rh- person receives
an Rh+ blood transfusion, however, the immune system starts to make anti-Rh
antibodies that will remain in the blood. If a second transfusion of Rh+ blood is given
later, the previously formed anti-Rh antibodies will cause agglutination
and hemolysis of the RBCs in the donated blood, and a severe reaction may occur.
Plasma Proteins
Plasma proteins are the major components of plasma. They consist of albumin,
globulin, and fibrinogen. Most plasma proteins are manufactured in the liver. Some
plasma proteins (immunoglobulins/ antibodies) are made by specific lymphocytes.
The plasma proteins have varied functions.
They serve to maintain the pH of the blood at 7.4. Some protein components are
antibodies that recognize specific antigens. A few of the clotting factors are proteins.
Some proteins serve as transport carriers for hormones, metals, amino acids, fatty
acids, enzymes, and drugs.
Because the protein molecules are large and the capillary walls are impermeable to
them, substances escape filtration by the kidneys and stay longer in the blood when
they are bound to proteins. The protein fractions exert an osmotic force of about 25
mm Hg across the capillary wall. This force tends to pull water into the blood from
the surrounding fluid compartments, such as the interstitial compartment, and
maintains the blood volume.
In individuals with protein deficiency, the reduction of this force is responsible for
the edema that develops.
Cerebrospinal fluid
Embedded within the brain are four ventricles or chambers that form a
continuous fluid-filled system. In the roof of each of these ventricles is a
network of capillaries referred to as the choroid plexus. It is from the
choroid plexuses of the two lateral ventricles (one in each cerebral
hemisphere) that cerebrospinal fluid (CSF) is primarily derived. Due to
the presence of the blood–brain barrier, the selective transport
processes of the choroid plexus determine the composition of the CSF.
Therefore, the composition of the CSF is markedly different from the
composition of the plasma. However, the CSF is in equilibrium with the
interstitial fluid of the brain and contributes to the maintenance of a
consistent chemical environment for neurons, which serves to optimize
their function.
The CSF flows through the ventricles, downward through the central
canal of the spinal cord, and then upward toward the brain through the
subarachnoid space that completely surrounds the brain and spinal cord.
As the CSF flows over the superior surface of the brain, it leaves the
subarachnoid space and is absorbed into the venous system. Although
CSF is actively secreted at a rate of 500 ml/day, the volume of this fluid
in the system is approximately 140 ml. Therefore, the entire volume of
CSF is turned over three to four times per day.
The one-way flow of the CSF and the constant turnover facilitate its
important function of removing potentially harmful brain metabolites.
The CSF also protects the brain from impact by serving as a shockabsorbing system that lies between the brain and its bony capsule.
Finally, because the brain and the CSF have about the same specific
gravity, the brain floats in this fluid. This reduces the effective weight of
the brain from 1400 g to less than 50g and prevents compression of
neurons on the inferior surface of the brain.
The Lymphatic System
In general, the fluid moving out of the capillaries exceeds that entering it from the
interstitial fluid compartment. Also, large protein particles tend to accumulate in this
compartment. These proteins may be particles that have leaked from the blood into
the capillaries, cell waste products, or remains of dead tissue.
Being large, these proteins cannot be easily removed by the capillaries, however,
another mechanism—the lymphatic system—is in place to remove excessive fluid
and proteins.
FUNCTIONS OF THE LYMPHATIC SYSTEM
The function of the lymphatic system is to return excess fluid and protein from the
interstitial fluid compartment back into the blood circulation. If the protein is not
returned to the blood, the plasma colloid osmotic pressure will drop, and it will not be
possible for fluid to stay inside the circulatory system.
Defense is another important function of this system. Lymphoid tissue is responsible
for the production, maintenance, and distribution of lymphocytes, a class of white
blood cells that participates in defense.
The white blood cells in the lymphatic system remove foreign agents that have
entered the interstitial region.
In the intestine, lymphatics help carry fat and large particles to the liver. In the kidney,
adequate lymphatic flow is required for concentrating the urine.
Lymph Vessels
The lymphatic system is similar to the cardiovascular system because it, too, has
vessels, often called lymphatics. Lymphatics are present in almost all the regions
of the body; however, they are absent from the central nervous system and such
regions as the cornea, lens, cartilage, and epithelium that lack a blood supply.
The smallest vessels—the lymphatic capillaries— arise as blind-ended tubes in the
interstitial spaces. These capillaries have thinner walls, and they are larger than blood
capillaries. The lymph capillaries are highly permeable and allow large particles to
easily enter the vessel. The endothelial cells lining the capillaries have gaps that allow
the particles to enter. In addition, the cells overlap with each other, with the overlap
acting as one-way valves.
Anchoring filaments—proteins attached to the endothelial cells—also help adjust the
width of the gaps. When there is more fluid inside the lymph capillaries, the width of
the gap becomes smaller, allowing less fluid in and preventing backflow of fluid.
When there is more fluid in the interstitial compartment, the anchoring filaments are
pulled and the gap widens, allowing more fluid to enter the capillaries.
The lymph capillaries in the intestines (lacteals) are located in the center of the villi.
The lymph in the lacteal carries a high fat content, giving the lymph a creamy, white
appearance. Lymph flowing through the lacteals is referred to as chyle.
From the periphery, the networks of capillaries join and rejoin others to form larger
lymphatic vessels. The lymphatic vessels resemble veins, with an endothelium,
smooth wall muscles, and adventitia. The inner lining of these large vessels is thrown
into folds to form valves. Lymph vessels have numerous valves located every few
millimeters, giving the vessels a beaded appearance. At various intervals, the lymph
vessels open into lymphatic tissue called lymph nodes. Lymphatic vessels from the
lymph nodes join others and progressively become larger until they communicate
with two collecting vessels, the thoracic duct or left lymphatic duct, the largest of
these vessels, and the right lymphatic duct. The lower end of the thoracic duct is
enlarged and is known as the cisterna chyli. The thoracic duct and the right lymphatic
duct are located in the thoracic cavity. The thoracic duct is about 38–45 cm (15–17.7
in) long and runs parallel to the vertebral column. The right lymphatic duct is much
shorter, about 1.5 cm (0.6 in) long. Both ducts open into the blood vessels in the neck
(on the left and right side, respectively) at the junction of the subclavian and internal
jugular vein. Thus, lymph is emptied into the blood circulation. The thoracic duct
collects lymph from the left side of the body and from the right side of the body
inferior to the diaphragm. The right lymphatic duct collects The thoracic duct and the
right lymphatic duct are located in the thoracic cavity. The thoracic duct is about 38–
45 cm (15–17.7 in) long and runs parallel to the vertebral column. The right lymphatic
duct is much shorter, about 1.5 cm (0.6 in) long. Both ducts open into the blood
vessels in the neck (on the left and right side, respectively) at the junction of the
subclavian and internal jugular vein. Thus, lymph is emptied into the blood
circulation.
The thoracic duct collects lymph from the left side of the body and from the right side
of the body inferior to the diaphragm. The right lymphatic duct collects
Lymph and Lymph Flow
The lymph or lymph fluid, a clear, pale yellow fluid, is the overflow fluid from the
tissue spaces with the same composition as the interstitial fluid. It carries large
proteins and waste from different parts of the body.
Lymph vessels, unlike blood vessels, do not have extensive smooth muscle around
them to aid the flow. Also, the lymphatic system does not have a pump equivalent to
the heart to circulate the fluid. This system, therefore, must rely on other mechanisms
to move the fluid toward the neck. Lymph vessels have one-way valves to help direct
the fluid. Lymph is also propelled to a large extent by the passive and active
movements of skeletal muscles. In addition, the pulsation of arteries lying close to the
lymph vessels helps propel the lymph. Another important mechanism that draws the
lymph upward is the respiratory movements. When a person inspires, the pressure
drops in the thorax and increases in the abdomen. This difference in pressure is
sufficient to “suck” the lymph into the thorax and the venous system.
Changes in posture, passive compression, and massage can also aid lymph flow. The
smooth wall muscles of the lymphatic vessels also help move lymph by contracting
when distended. The rate of flow increases with physical activity. It has been
estimated that about 2–4 liters of lymphatic fluid and the equivalent of 25% to 50% of
the total circulating plasma protein is returned to the circulation every day.