BLOOD

CARDIOVASCULAR SYSTEM

By the time a human embryo is a only few mm in size, it needs energy & produces wastes faster than diffusion can remove. A system to perform transport is needed and thus by the end of the 3rd week the heart beats while other organ systems have barely begun. Fluid necessary in body since the differentiated cells of the body can't get their own food or move away from their wastes. These specialized cells are also less able to protect themselves from temperature changes, pH changes, & toxic chemicals. The cardiovascular system must help control the composition of the fluid which bathes the cells. Blood therefore serves three main functions:

--it transports oxygen, nutrients, heat, wastes, hormones, & enzymes

--it regulates pH with buffers; the water in blood resists temperature change

--it protects the body from blood loss & microbes

BLOOD

Blood represents about 8%of the human body weight: this is 5-6 liters in average male and 4-5 liters in the average female. When blood is centrifuged (spun) the components of blood are separated according to weight. Blood is 55% plasma, 45% formed elements (blood cells). The blood cells can be divided into red blood cells (erythrocytes), white blood cells (leukocytes), and platelets.

hematocrit

A) PLASMA

Plasma is 91.5% water, 7% protein, 1.5% other (wastes, urea, hormones, creatine, ammonia). Most of the blood proteins are made in the liver. Their roles include transport, fighting disease, controlling the movement of water, and clotting.

B) ERYTHROCYTES (red blood cells)

Erythropoiesis (the process of making red blood cells) begins as proerythroblasts synthesize the protein hemoglobin. At later stages, the nucleus is ejected from the cell and the cell becomes biconcave. The flexible biconcave cells can squeeze through the endothelial cells lining the marrow and enter the blood. Hemoglobin contains a protein portion (globin) and a non-protein heme group that binds oxygen.

hemoglobin

There are 5.2 million red blood cells per ml of blood in a male, 4.8 million per ml in a female. The amazing total of 25 trillion cells in an adult humans means that red blood cells compose about 1/3 the cells in the human body! More than 99% of blood cells are red blood cells. One third of the weight of a red blood cell is hemoglobin which is made before the loss of the ribosomes and nucleus. Each cell has about 280 million molecules of hemoglobin.

As the saying goes, blood is thicker than water. The proteins in blood plasma make plasma thicker than water alone; the cells increase blood’s viscosity even more. Normally, rbcs compose 40% volume of the blood; this measure is called the hematocrit. (Once blood is centrifuged, the ratio of the volume of rbcs to the total blood volume is used to determine the hematocrit.) Hematocrits in men are higher than in women on average (due to the effects of testosterone and menstruation

Hemoglobin is the respiratory pigment in vertebrate red blood cells. The following images are of blood smears of a bony fish, frog, turtle, and human. The human slide shows a reticulocyte, the precursor to circulating red blood cells which has not yet ejected its nucleus.

fishfrog

turtlehuman

Sickle Cell Anemia

In the genetic disorder sickle cell anemia, a mutation which affects the shape of the protein hemoglobin can alter the shape of red blood cells (because they contain so much hemoglobin). These abnormally shaped cells can clog capillaries and block blood flow to tissues.

sickle cell anemia

The chains of sugar molecules on the surfaces of red blood cells (or the lack of them) determine a person's blood type. A person's immune system will attack sugar chains which are perceived as foreign.

blood typeblood type

2) LEUKOCYTES (white blood cells)

Most leukocytes are located in peripheral tissues rather than in the blood, only about 2% are actually in the blood. They travel through blood looking for disturbances in your body's normal functioning. If they detect the appropriate signal, demonstrate both chemotaxis (the ability to move towards the signal) and emigration or diapedesis (they can fit between small spaces between cells and pass through capillary walls due to their ability to move in an amoeboid fashion). Microbe toxins, colony stimulating factors, & kinins (produced by damaged tissues) may attract leukocytes (especially neutrophils & macrophages).

Some leukocytes (neutrophils, macrophages, monocytes) phagocytize (engulf) microbes and may kill with chemicals such as lysozyme, defensins, & strong oxidants. Eosinophils undergo the exocytosis of these chemicals onto parasites that are too large for phagocytosis. Basophils facilitate the inflammatory response. Most leukocytes live only a few days and during an infection they may only survive a few hours. Because they are so short-lived, 75% of blood cells made by the bone marrow (perhaps 4-6 million per second are leukocytes.

Neutrophil

neutrophil neutrophil

Eosinophil

eosinophil eosinophil

Monocyte (which mature into macrophages)

monocyte monocyte

Lymphocyte

lymphocyte lymphocyte

Basophil

basophil


The types of white blood cells have fixed percentages in the blood and a differential white blood cell count examines these percentages. Changes from normal values may be useful in diagnosing a patient's problem:


--neutrophils increase due to burns, stress, inflammation, & bacterial infections; decrease after radiation and in B12 deficiencies
--eosinophils increase due to allergies, parasitic infections, and autoimmune diseases; decrease in stress and Cushings syndrome
--basophils: increase in allergies, hypersensitivities, cancers, hypothyroidism; decrease during pregnancy, ovulation, stress, hyperthyroidism
--lymphocytes: increase in viral infections, immune disorders, some leukemias
--monocytes: increase in viral or fungal infections, tuberculosis


Leukemia is the uncontrolled production and accumulation of immature leukocytes; since this decreases the numbers of red blood cells and platelets made, leukemia patients are in danger of anemia, hemorrhaging, and infection.

Note the abnormally high numbers of white blood cells (staining purple) in the blood from a leukemia patient in the following images.
leukemia leukemia

3) PLATELETS:

In the bone marrow, very active cells known as metamegakaryocytes shed bits of cytoplasm surrounded by cell membrane into the bloodstream, these are known as platelets. The average metamegakaryocyte produces 1000-1500 platelets and there are 250,000-400,000 platelets per ml of blood. They are only 2-4 um in size and have no nucleus. They are full of granules that have chemicals to promote clotting. They live only about 5-9 days and are visible as the small purple cells between the red blood cells in the following images..

plateletsplateletplatelets
Normally, platelets are repelled from each other and the blood vessel walls.

platelets

Platelets have 3 functions after bleeding begins: they form a platelet plug to block the break in the blood vessel, they induce coagulation (form a fibrin clot), and they help maintain endothelial lining of blood vessels. After vascular damage has occurred, platelets release their granules, form a platelet plug (in the first image below), and induce the blood protein fibrinogen to form the fibrin of the blood clot (second image).

clotting

clotting


Fibrinolysis is the dissolution of clots; no clot is meant to last forever. Clots which have formed inappropriately can be dissolved as well.


Anything floating in the blood (even an air bubble) that may potentially block a blood vessel is called an embolus. Inappropriate clots may form such plugs in undamaged blood vessels in a process known as thrombosis.
Thrombolytic agents (kallikrein, tPA, streptokinase) can be injected into the body to dissolve clots. Anticoagulants (such as heparin and warfarin) prevent blood from clotting in the first place
Platelets may start the formation of clots in response to irregular endothelial surfaces, artificial heart valves, or endothelial lipid plaques
Low daily doses of aspirin decreases the formation of a thrombus (by inhibiting the clotting factor thromboxane) and thus decrease the risk of heart attack and stroke.
Hemophilia is a genetic disease caused by the inability to make a clotting factor. Hemophiliacs are in danger of hemorrhage if they are cut. There are different kinds of hemophilia but each involves the lack of a clotting factor. Hemophilia types A and B are sex-linked while type C isn't. Tragically, most hemophiliacs who received blood transfusions through 1982-85 were contaminated with HIV.