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
↑ ↓
SYNOVIAL FLUIDS, ETC
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
- Water (90%)
- Dissolved substances (10%)
- Proteins
- Albumin (egg white). Most common protein in blood (homeostasis)
- Antibodies
- Clotting factors called fibrinogen and fibrin.
- Lipoproteins (move fats through blood: HDL, LDL)
- Nutrients
- Glucose (main energy source)
- Amino Acids (builds proteins)
- Wastes (urea)
- Gases (O2, CO2, Nitrogen)
- Electrolytes = ions (Na+, K+, Cl-, Ca++)
BLOOD CELLS
- 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.
- They have no nucleus
- Filled with hemoglobin (Hgb), which carries O2 throughout the body. Oxygenated Hgb is bright red, deoxy Hgb is a deeper red.
- Average life span is 120 days. Old ones are destroyed in the spleen and liver, and Hgb is recycled. Every day, about 100 billion of these cells are destroyed, and 100 billion are made: where? Red 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)
- Hereditary spherocytosis
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.
Hereditary spherocytosis
The red blood cells shrink over time due to problems with the red blood cell membrane.
Many of the RBC’s look small and round.
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.)
Mean Corpuscular Volume
Mean corpuscular volume (MCV) is a measurement of the average size of your RBCs.
The MCV is elevated when your RBCs are larger than normal (macrocytic), for example in anemia caused by vitamin B12 deficiency.
When the MCV is decreased, your RBCs are smaller than normal (microcytic) as is seen in iron deficiency anemia or thalassemias.
Mean Corpuscular Hemoglobin
Mean corpuscular hemoglobin (MCH) is a calculation of the average amount of oxygen-carrying hemoglobin inside a red blood cell.
Macrocytic RBCs are large so tend to have a higher MCH, while microcytic red cells would have a lower value.
Mean Corpuscular Hemoglobin Concentration
Mean corpuscular hemoglobin concentration (MCHC) is a calculation of the average concentration of hemoglobin inside a red cell.
Decreased MCHC values (hypochromia) are seen in conditions where the hemoglobin is abnormally diluted inside the red cells, such as in iron deficiency anemia and in thalassemia.
Increased MCHC values (hyperchromia) are seen in conditions where the hemoglobin is abnormally concentrated inside the red cells, such as in burn patients and hereditary spherocytosis, a relatively rare congenital disorder.
Red Cell Distribution Width
Red cell distribution width (RDW) is a calculation of the variation in the size of your RBCs.
Having RBC’s with various shapes is called aniscocytosis.
Having RBC’s with various shapes is called poikilocytosis.
In some anemias, such as pernicious anemia, anisocytosis and poikilocytosis causes an increase in the RDW.
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.
Microbiology
To understand the function of white blood cells, you will need to learn some general concepts and terminology from Microbiology:
–Pathogen
–General size of bacteria and viruses
–Antigen
Pathogen “Path” = disease “ogen” = generating
A pathogen is something that causes disease.
A biological pathogen is a bacterium, virus, fungi, yeast, protozoa, worms, etc.
A non-biological pathogen can be a toxic chemical, asbestos, etc.
Usually, the term “pathogen” refers to a biological pathogen.
Sizes of Pathogens
Bacteria are so small that hundreds of them can fit inside one white blood cell. However, bacteria usually do not invade body cells. They live between the cells of the body, using up nutrients in the area, and they cause harm by secreting toxins.Viruses are so small that thousands of them can fit inside the NUCLEUS of one white blood cell.They always try to invade body cells because they need a piece of our DNA or RNA in order to replicate.When a body cell has been invaded by a virus, the entire cell must be killed by a white blood cell.
Antigen
An antigen is anything that causes an immune response, which isn't necessarily a biological pathogen (disease-causing organism).
A non-biological antigen can be pollen, dust, grass, or anything that a person is allergic to.
Pollen can be an antigen to a person with allergies, but it is not an antigen to a person without allergies, because no immune response was launched.
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.
What’s the Difference between Neutrophils and Monocytes/Macrophages?
There are 10x more neutrophils in the bloodstream than monocytes/Macrophages. Consider neutrophils to be the most numerous white blood cell.
However, there are more macrophages in the tissues of the body. They are everywhere!
Neutrophils live only a few days. Monocytes/Macrophages live a few months. Lymphocytes live for years.
Monocytes/Macrophages are larger and slower than neutrophils, but they can phagocytize larger organisms and more of them.
Neutrophils usually just phagocytize bacteria until they die. Macrophages phagocytize and then take pieces of the dead bacteria and present them to lymphocytes so a larger immune response can occur.
There are two types of phagocytes: Neutrophils and macrophages.
Neutrophils and macrophages both mainly function by phagocytizing bacteria (not viruses).
Neutrophils and macrophages eat bacteria more easily after an antibody attaches to the bacteria. This is called an antigen-antibody complex. The antibody enables the neutrophil or macrophage to grab onto the bacteria more easily.
Lymphocytes are mostly needed to kill off body cells infected by viruses.
Neutrophils just phagocytize bacteria and secrete chemicals to recruit more white blood cells to the site.
Unlike neutrophils, macrophages have surface receptors; these "recognize" the surface of the pathogen’s cell membrane.
Macrophages phagocytize the bacteria, pop their lysosomes onto it, and dissolve it, except for some pieces of the bacteria’s cell membrane.
The macrophage places these pieces of bacteria on its own cell membrane, and finds a lymphocyte to present it to.
Macrophages present these pieces to T cell lymphocytes and to B cells lymphocytes.
The lymphocyte feels the shape of the bacteria pieces on top of the macrophage, (this is called “antigen presentation”) and the lymphocyte can then launch an attack on the rest of the bacteria still alive in the body.
In this way, the macrophage recruits even more lymphocytes to join the war.
So, what is a lymphocyte?
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