BLOOD

Blood is not an epithelial tissue, and it’s not loose or dense connective tissue; it’s classified as a “special connective tissue”. You have about 5 liters of blood, but that is only half of the body fluid. The other half includes fluid around each cell, and joint fluids, etc.

PLASMA  EXTRACELLULAR FLUID

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SYNOVIAL FLUIDS, JOINTS, CSF

Blood consists of the following:

A.Plasma

B.Red blood cells

C.White blood cells

D.Platelets

Plasma is what the blood cells float around in. If you spin a blood sample in a test tube, the red blood cells sink to the bottom, and you’ll see the yellow plasma on top. Some people who need blood just need the packed RBCs, others need the plasma, and some need whole blood, which is both plasma and RBCs. The plasma also carries around the platelets and some white blood cells.

PLASMA CONTENTS

  1. Water (90%)
  2. Dissolved substances (10%)
  3. Proteins
  4. Albumin (egg white). Most common protein in blood (needed for homeostasis of blood volume and blood pressure)
  5. Antibodies
  6. Clotting factors; main one is called fibrin.
  7. Lipoproteins (move fats through blood: HDL, LDL)
  8. Nutrients
  9. Glucose (main energy source)
  10. Amino Acids (builds proteins)
  11. Wastes (urea)
  12. Gases (O2, CO2, Nitrogen)
  13. Electrolytes = ions (Na+, K+, Cl-, Ca++)

BLOOD CELLS

  1. ERYTHROCYTES (Red blood cells): These are among the smallest cells in the body. There are about 5 million of them in each of us. Their structure is simple; like a doughnut with the hole not fully cut out.
  2. These are among the smallest cells in the body
  3. They have no nucleus
  4. Biconcave to increase surface area
  5. Filled with hemoglobin (Hgb), which carries O2 throughout the body. Oxygenated Hgb is bright red, deoxy Hgb is deeper red, almost a bluish-purple.
  6. Hemoglobin consists of 2 alpha units and 2 beta units. Hemoglobin abnormalities are classified by which unit is deformed. The heme group is where the oxygen molecule binds. An iron (Fe++) molecule is in the middle, which attracts the oxygen to the heme group.
  7. Average life span is 120 days. Old ones are destroyed in the spleen and liver, and Hgb and iron are recycled.
  8. In one day, 100 billion of these cells are destroyed, and 100 billion are made: where?
  9. Red bone marrow.

DISORDERS OF RBCs

POLYCYTHEMIA is too many red blood cells; can cause blood clots. Need to donate blood frequently.

ANEMIA: Anemia can be caused by many things:

–Too few RBC’s

–Iron deficiency

–Hemorrhagic anemia (person lost blood)

–Hemolytic anemia (immune disorder, infection, blood transfusion)

  • G6PD deficiency

–Hemoglobin abnormalities

  • Pernicious anemia (lack of vitamin B12 or intrinsic factor)
  • Thalassemia
  • Sickle cell disease
  • Megaloblastic anemia (pernicious anemia)

ANEMIA: Any condition of RED BLOOD CELLS in which the blood’s capacity for carrying oxygen is diminished.

HYPOXIA is lack of oxygen to tissues.

It can be caused from:

Ischemia (reduced blood flow to a tissue)

Malfunctioning hemoglobin

Increasing altitude

Characteristic sign of anemia: see reticulocytes in the blood (immature red blood cells). Remnants of the nucleus are still in the cell.

DETAILS ABOUT SOME TYPES OF ANEMIA

Hemolytic anemia (immune disorder, infection, blood transfusion)

Hemolysis means rupture of RBC’s. Hemolytic anemia can be hereditary (born with the genes that cause the disease) or acquired. Hereditary factors include immune disorders and G6PD deficiency. Acquired causes include infections (malaria), and receiving the wrong blood type in a transfusion.

G6PD deficiency (hereditary, X-linked; almost all are males)

G6PDH is an enzyme which is important for RBC metabolism. G6PD is the most common human enzyme defect. A person with this would have a hard time maintaining iron in a reduced state, and they develop hereditary (NOT acquired) hemolytic anemia in response to a number of causes, most commonly infection or exposure to certain medications, chemicals, or ingestion of fava beans.

HEMOGLOBINOPATHIES (HEMOGLOBIN ABNORMALITIES)

Pernicious anemia(Megaloblastic anemia)

Caused by lack of vitamin B12 or intrinsic factor

When a person has gastric bypass surgery, the stomach is no longer able to produce intrinsic factor, which is needed to absorb vitamin B12, which is needed to make hemoglobin in RBC’s.

Without this vitamin, the blood cells are fewer and much larger than normal (megaloblastic). The surgery patient must take vitamin B12 shots or sublingual supplements for the rest of their life.

Thalassemia

A hereditary form of anemia where the RBCs have abnormal hemoglobin that deforms the cells into many types of unusual shapes, including spherocytes (small and round), target cells (looks like a target) and tear drops.

Sickle cell disease

A hereditary mutation resulting in one valine amino acid substituted for glutamic acid.

Present in African Americans more than in other groups, and is always characterized by sickled erythrocytes.

The sickle shape helps prevent malaria infections, but it also causes blood clots.

BLOOD TESTS FOR RBCs

RBC, Hgb, Hct

Red blood cell (RBC) count is a count of the actual number of red blood cells per volume of blood. Both increases and decreases can point to abnormal conditions.

Hemoglobin (Hgb) measures the amount of oxygen-carrying protein in the blood.

Hematocrit (Hct) measures the percentage of red blood cells in a given volume of whole blood.

HEMATOCRIT

A quick screening test for anemia is the hematocrit.

A drop of blood is drawn up a small glass capillary tube and the tube is centrifuged to pack the red blood cells at the bottom with the plasma on top.

Hematocrit measures the percentage of blood volume that consists of erythrocytes.

The hematocrit is the ratio of packed red blood cells to total blood volume.

Normal is about 45% (46% for men and 38% for women.)

BLOOD TYPING:The ABO SYSTEM

Blood typing is the technique for determining which specific protein type is present on RBCs.

Only certain types of blood transfusions are safe because the outer membranes of the red blood cells carry certain types of proteins that another person’s body will think is a foreign body and reject it.

These proteins are called antigens (something that causes an allergic reaction). There are two types of blood antigens: Type A and Type B.

A person with Type A antigens on their blood cells have Type A blood.

A person with Type B antigens have Type B blood.

A person with both types has type AB blood.

A person with neither antigen has type O blood.

If a person with type A blood gets a transfusion of type B antigens (from Type B or TypeAB, the donated blood will clump in masses (coagulation), and the person will die.

The same is true for a type B person getting type A or AB blood.

Type O negative blood is called the universal donor, because there are no antigens, so that blood can be donated to anyone. Type AB positive blood is considered the universal acceptor, because they can use any other type of blood. This blood type is fairly rare.The rarest blood type is AB negative.

RH FACTOR

There is another term that follows the blood type. The term is “positive” or “negative”. This refers to the presence of another type of protein, called the Rh factor. A person with type B blood and has the Rh factor is called B-positive.

A person with type B blood and no Rh factor is called B-negative.

The reason this is so important is that if an Rh- mother has an Rh+ fetus in her womb (from an Rh+ father), her antibodies will attack the red blood cells of the fetus because her body detects the Rh protein on the baby’s red blood cells and thinks they are foreign objects. This is called Hemolytic Disease of the Newborn (HDN).

This can be prevented if the doctor knows the mother is Rh- and the father is Rh+, because that means the baby has a 50% chance of being Rh+ like the father.

Therefore, anytime a mother is Rh-, even if the mother says the father is Rh-, you can’t be sure who the father is, so they will proceed as though the baby may be Rh +.

They will give her an injection of a medicine (rhogam) that will prevent her immune system from attacking the baby.

Rhogam

Rhogam is given at 18 weeks into the pregnancy and again within 72 hours after giving birth.

It is usually given within 2 hours after giving birth since you can’t trust the patient to return after they leave the hospital.

The first baby is not at risk; during the first birth, the placenta tears away and that’s when the baby’s blood cells get into the mother’s bloodstream.

She then forms antibodies against the Rh factor, which are ready to attack the second fetus.

The baby does not make the Rh factor until about 18 weeks into the pregnancy.

LEUKOCYTES (White blood cells):There are different kinds; all fight infection.

1) BASOPHILS: Few in body. Their blue granules are filled with histamines, which help fight infection by vasodilation, increasing the number of WBCs to the infection site. Antihistamines interfere with the function of basophils.When a basophile leaves the circulation to enter the tissues, it becomes a MAST CELL.

2) EOSINOPHILS:Function to fight allergies and parasitic infections. During these conditions, their numbers increase.

3) NEUTROPHILS: The most abundant type of WBC. They are the first to respond to infection. They phagocytize (eat) bacteria and also destroy bacterial toxins in body fluids. Nucleus – has two to six lobes

  • Neutrophils are the white blood cells that contribute to immunity mainly by engulfing BACTERIA and foreign bodies (thorns, dirt, etc) in a process called phagocytosis.
  • They release the contents of their lysosomes onto the invader, dissolving it.
  • When a bacterium has a capsule, it makes it hard to phagocytize, so the neutrophil requires opsonization by antibodies.
  • Some bacteria have evolved a slippery capsule around them as a defense against phagocytosis. The neutrophil cannot engulf this type of bacteria. Neither can a macrophage.
  • When an antibody attaches to this type of bacteria, the neutrophil can now grab onto the antibody like a handle, enabling it to phagocytize the bacteria.
  • This process of facilitation of phagocytosis is called OPSONIZATION.
  • When the invader has the antibody attached to it, it is called an ANTIGEN-ANTIBODY COMPLEX.
  • If a bacterium does not have a capsule, the neutrophil can destroy it without opsonization. The antibody can also destroy the bacterium by itself by popping the cell membrane.
  • But when a capsule is present, the neutrophil and antibody work best together.
  • Neutrophils are also the ones that primarily destroy the dissolved toxins that bacteria secrete into body fluids.

4) MONOCYTES:Like neutrophils, they phagocytize (eat) bacteria, old cells, and foreign bodies. They have more types of lysosome enzymes than neutrophils so they are better at killing difficult pathogens.They also use antibodies for opsonization.

  • When they leave the bloodstream and enter the tissues, they are calledMACROPHAGES.

5) LYMPHOCYTES: Effective in fighting infectious organisms like body cells infected with viruses They act against a specific foreign molecule (antigen)

Two main classes of lymphocyte

–B cells – Originate in the bone marrow, mature into plasma cells. A mature plasma cell fights infection by producing antibodies

–T cells – Originate in the thymus gland. They attack foreign cells directly (including organ transplants!)

B CELLS: – mature into plasma cells

PLASMA CELLSsecrete antibodies; the antibodies are what kill the attacking cell. Antibodies attack in two ways:

–They attach to bacteria and pop the cell membrane

–They attach to encapulated bacteria to help neutrophils phagocytize them.

Mononucleosis: Epstein Barr virus attacks B lymphocytes. It is characterized by inflammation of lymph vessels (lymphangitis). Lymphangitis: lymph vessel inflammation; usually from infection. Infected lymphocytes have a

characteristic scalloped edge where they touchRBC’s

T CELLS

1.Coordinate the immune response by recruiting other white blood cells

2.They can directly destroy bacteria by popping their cell membrane.

3.They can also destroy body cells infected with viruses.

4.T cells attack foreign cells directly by popping the cell membrane.

5.They do not need to phagocytize the invading cell. They do not need the assistance of antibodies.

6.T-cells can therefore kill a body cell that has become infected with viruses.

7.T cells are the cells that attack organ transplants!

8.Immunosuppression drugs are designed to inhibit the action of T cells.

9.T cells are attacked by the HIV (AIDS) virus.

10.The thymus gland secrets certain hormones which can cause T cells to become immunocompetent (makes the cells mature and start to work)

There are several types of T cells. The main types are

Cytotoxic (Killer) T cells

–Go out and directly kill bacteria or infected host cells

Helper T cells

–Release chemicals called “cytokines” to stimulate the B cells to produce antibodies against the bacteria. Cytokines also call in more white blood cells of all types to join in the war.

Suppressor T cells

Stop the immune process when it is over, and also "tell" some B-Cells to "remember" how to destroy that specific pathogen. Those B-cells then become Memory B-Cells. They can react to the same pathogen faster, the next time it invades. Memory B-cells already have the proper antibodies stored up for that pathogen.

Summary

A pathogen somehow gets past the body's physical and chemical barriers and the inflammation response.

The pathogen is engulfed by a macrophage (or neutrophil).

The macrophage releases the contents of its lysosomes onto the bacterium and dissolves most of it. There are still some pieces of the bacterium’s cell membrane left. The macrophage then forces the surface proteins of the bacterium (antigens) to it's own cell surface.

Helper T-Cells touch these surface antigens, make a copy of their shape, and present them to B-cells to make antibodies against them.

These Helper T-Cells begin to multiply and have two main roles.

The first is to activate B-Cells and "tell" them how to neutralize the pathogen by presenting the pieces of the bacterium cell membrane so the B-cells can make antibodies.

The B-Cells (now called Plasma cells because they have been activated) begin to multiply and produce the antibodies to neutralize this specific pathogen.

The second role of Helper T-Cells is to activate the Killer T-Cells.

Killer T-Cells can either destroy the pathogen itself (bacteria), or destroy the entire body cell which is infected (viruses).

When the immune response is over, Suppressor T-Cells stop the process and also "tell" some B-Cells to "remember" how to destroy that specific pathogen. Those B-cells now become Memory B-Cells.

DISORDERS OF WBCs

LEUKEMIA: Cancer of the blood is called leukemia. It actually only involves the white blood cells. Something goes wrong in one stem cell, and it starts making huge amounts of clones of itself which don’t work right and not enough normal white blood cells are made. Therefore, the body cannot fight infection. It’s better to send a young cell with no weapons to the war than to send nothing at all!

There are many types of leukemias.

Think of Leukemia as too few mature white blood cells.

–Classified as lymphoblastic (too many immature lymphocytes) or

–myeloblastic (too many immature neutrophils)

People with severe leukemia may need a bone marrow transplant.

First, all of their WBC’s have to be killed off with a medicine because they are mostly malfunctioning anyway.

A donor has a small cylinder of bone removed from their hip. This is ground up and given by i.v. to the recipient.

The new WBC’s may kill the patient or it may save their life. It is done as a last resort.

WBC Count

White blood cell (WBC) count is a count of the actual number of white blood cells per volume of blood. Both increases and decreases can be significant.

White blood cell differential looks at the types of white blood cells present. There are five different types of white blood cells, each with its own function in protecting us from infection. The differential classifies a person's white blood cells into each type: neutrophils (also known as segs, PMNs, granulocytes, grans), lymphocytes, monocytes, eosinophils, and basophils.

Terms

Excess neutrophils: neutrophilia

Few neutrophils: neutropenia

Antibodies

Antibodies (also known as immunoglobulins, abbreviated Ig) are proteins made by plasma cells.

They are used to identify and neutralize foreign objects, such as bacteria and viruses.

They are typically made of basic structural units—each with two large heavy chains and two small light chains—to form a unit shaped like the letter “Y”

The tips of the “Y” have receptors that are specific for a particular antigen.

The stem of the “Y” can be grasped by a phagocyte.

The small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen binding sites, to exist.

This region is known as the hypervariable region. Each of these variants can bind to a different target, known as an antigen.

This huge diversity of antibodies allows the immune system to recognize an equally wide diversity of antigens.

IMMUNITY:B Cells that have matured into plasma cells which have made antibodies are now called Memory lymphocytes, after their first war.

Most people are sick more often as children than as adults in their 20s through 30s because we build up many varieties of MEMORY LYMPHOCYTESduring childhood, providing immunity from more and more antigens during adulthood.