Blood

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What makes up Hemoglobin

4 protein chains (globins) and a heme molecule with an iron ion

Types of globin chains?

Two alpha chains and two beta chains

How many of each globin chains are in adult hemoglobin?

Two alpha, two beta. the four pelypeptide chains each bind to a ringlike hemegroup.

What is significant about fetal globin?

It has a higher affinity for oxygen than adult hemoglobin. Contains two alpha and two gamma polypeptide chains per globin molecule. after birth, fetal erythrocytes carrying hemoglobin F are rapidly destroyed by the liver and the babies erythrocytes begin producing hemoglobin A (adult hemoblin).

What binds to the iron? How many molecules of this can bind to each hemoglobin?

a hemoglobin can transport four molecules of oxygen because each iron atom can combine reversibly with one molecule of oxygen. a single red blood cell contains about 250 million hemoglobin molecules.

What is the name of hemoglobin when it is bound to oxygen?

oxyhemoglobin

What percentage of oxygen in blood is bound to hemoglobin?

...

What color is hemoglobin when it is bound to oxygen?

Ruby Red

What is hemoglobin called when it is bound to carbon dioxide?

carbaminohemoglobin

What percentage of carbon dioxide in the blood is bound to hemoglobin?

20%

What is hemoglobin called when it is not bound to either carbon dioxide or oxygen?

deoxyhemoglobin

What color is blood when it is not bound to oxygen?

Dark Red

What is the name of Stem cells for erythrocytes?

Hemocytoblast, or pluripotent hematopoietic stem cell

The stem cells for erythrocytes are located in what type of tissue?

Red bone marrow

Where is red bone marrow found in adults?

Found chiefly in the bones of the axial skeleton and girdles, and in the proximal epiphyses of the humerus and femur

As the erythroblast matures, what happens to the size of the nucleus? To the cell?

The cell divides many times and hemoglobin is synthesied and iron accumulates as they turn into a late erythroblast and then a normoblast. when a normoblast has accumulated almost all of its hemoglobin, it ejects most of its organelles and its nucleus degenerates and is punched off (gets smaller then is gone, the cell gets smaller)

What is a reticulocyte?

a young erythrocyte. the result of the ejection of the organelles and the nucleus degenerating and pinching off, allowing the cell to collapse inward and eventually assume the biconcave shape. it contains a scant reticulum of clumped ribosomes.

How does a reticulocyte differ from a mature red blood cell?

they have a scant reticulum (network) of clumped ribosomes

Does a reticulocyte have hemoglobin?

yes

What is the expected percentage of reticulocytes in the blood?

1-2%

What does an increased number of reticulocytes in the blood indicate?

indicates abnormal rates of erythrocyte formation. too many erythrocytes is undesirably vicious. blood becomes too thick and its harder for heart to pump and to reach tissue.

What hormone(s) regulates RBC production?

eryhtopoietin (EPO), a glycoprotein hormone

What organ (s) release Eryhtopoietin or glyoprotein hormones?

kidneys play major role, but also liver

What is happening in the tissues of the body (what is there too little or too much of) that causes an increase in the release of erytoproietin or glycoprotein hormones?

When certain kidney cells become hypotoxic oxygen sensitive enzymes are unable to carry out their normal functions of degrading an intracellular signaling molecule called hypoxia-inducible factor (HIF), as HIF accumulates, it accelerates the synthesis and release of erythropoietin.

There are a number of substances that are needed for cells to divide and therefore are needed for erythropoiesis. There are 3 nutrients and 2 vitamin (or vitamin-like) substances. What are they?

nutrients (amino acids, lipids, and carbohydrates), iron, and Vitamin B12 and folic acid

Inadequate levels of a B vitamin are caused by the stomach producing low levels of a substance that is necessary for the B vitamin to be absorbed in the stomach. What B vitamin is involved and what substance is produced in the stomach?

Vitamin B12. an intrinsic factor produced by the stomach mucosa must be present for vitamin B12 to be absorbed by intestinal cells. consequently, the developing erythrocytes grow but do not divide, and large pale cells called macrocytes result.

What type of anemia occurs when the stomach does not produce enough intrinsic factor?

Pernicious anemia occurs usually when the intrinsic factor is deficient. Pernicious anemia is due to a deficiency of vitamin B12.

There is one ion that is needed only to make RBCs. What ion is this?

iron

What does iron bind to when it is transported in the blood?

bound to a transport protein called transferrin

What is iron called when it is bound to another molecule and stored within cells?

ferritin and hemosiderin

Destruction of Red Blood Cells

Macrophages in the spleen and liver phagocytize old RBCs (fragile, membranes beginning to break down)

How many days is the average lifespan of a Red Blood Cell?

100-120 days

What are the 3 major components of hemoglobin?

Heme, globin, iron

What is the fate of each of these components after the old RBCs have been phagocytized?

dying erythrocytes are engulfed and destroyed by macrophages.

Which component of RBC is broken down into its parts that are then used throughout the body?

The heme of their hemoglobin is slit off from globin. its core of iron is salvaged, bound to protein (as ferritin or hemosiderin) and stored for reuse.

Which component's final fate is to be excreted in the urine (making it yellow) and feces (making them various shades of brown)?

the balance of heme is degraded to bilirubin, a yellow pigment that is released to the blood and binds to albumin for transport. bilirunin is picked up by liver cells which in turn secrete it (in bile) into the interestine, where it is metabolized to urobilinogen and most of this degraded pigment leaves the body in feces as a brown pigment called stercobilin, the protein (globin) part of hemoglobin is metabolized or broken down to amino acids and released to the circulation.

When we describe a blood type, are we describing the type of antigens found on the surface of the cells or the antibodies found in the plasma?

Antigens found on the cells

One system of typing blood has four different categories (blood types) that can occur. For this system, we are not clear on why the antibodies develop when the infant has not been exposed to the antigen. Scientists think that maybe the infants are exposed to the antigen through the food they eat. Name each of the blood types and their antigens and antibodies (agglutinogens and agglutinins).

A (antigens- A, antibodies-B), B (antigens-B, antibodies-A), AB (antigens-none, anitbodies- A and B), and O (antigens-A,B, anitbodies- none).

When we do blood typing, we add the blood to test tubes that contain antibodies to the A antigen, antibodies to the B antigen and antibodies to the Rh antigen. If the blood clumps in test tube B, it indicates that the antibodies have bound to (agglutinized) the B antigens on the surface of the RBCs. This person has what type of blood?

type B

The Rh (or D) system is another system for typing blood. When we type for the Rh system, we say that a person is either _+__ or __-__ for the D antigen. If a person does not have the D antigen and they have not been exposed to D blood, do they have antibodies (agglutinins) for the D antigen?

Yes they have the D Antigen

What type of tissue is blood?

Connective tissue

blood Composition: major divisions and their amount

Plasma (55%)
Buffy coat (<1% of whole blood)
Red blood cells (45%)

What is the hematocrit?

% of the total volume of a blood sample. (erythrocytes normally consistute about 45% of total volume of a blood sample.)

What is an average hematocrit for males? For females?

normal hematocrit values in men is 47% +/- 5%. In females, it is 42% +/- 5%.

pH of blood

Slightly alkaline, with a pH between 7.35-7.45

Temperature of blood

(38 C or 100.4 F)

How much blood does a person have?

Blood accounts for about 8% of body weight.. males is about 5-6 L and females is about 4-5 L

Blood Transports and distributes what?

Distribution functions of the blood:
-delivering oxygen from the lungs and nutrients from the digestive tract to all body cells
-transporting metabolic waste products from cells to elimination sites (to the lungs for elimination of carbon dioxide, and to the kidneys for disposal of nitrogenous wastes in urine.
-transporting hormones from the endocrine organs to their target organs

Blood regulates what?

Regulatory function of the blood include:
-maintaining appropriate body temperature by absorbing and distributing heat throughout the body and to the skin surface to encourage heat loss
-maintaining normal pH in body tissues. many blood proteins and other blood borne solutes act as buggers to prevent excessive or abrupt changes in blood pH that could jeopardize normal cell activities. additionally, blood acts as the reservoir for the body's "alkaline reserve" of bicarbonate atoms.
-maintaining adequate fluid volume in the circulatory system/ salts (sodium chloride and others) and blood proteins act to prevent excessive fluid loss from the bloodstream into the tissue spaces. as a result, the fluid volume in the blood vessels remains ample to support efficient blood circulation to all parts of the body.

Blood protects against what? What components of blood are used in each type of protection?

Protective functions of the blood include:
-preventing blood loss. when a blood vessel is damaged, platelets and plasma proteins initiate clot formation, halting blood loss.
-preventing infection. drifting along in blood are antibodies, complement proteins, and white blood cells, all of which help defend the body against foreign invaders such as bacteria and viruses.

Plasma : Plasma is made up of what types of molecules

1. water (what percentage?)
90% of plasma volume - it is the dissolving and suspending medium for solutes of blood; absorbs heat
2. proteins (what percentage?)
plasma proteins make up 8% of volume. they all contribute to osmotic pressure and maintain water balance in blood and tissues; they all have other functions as well.

What are the three major proteins in blood?

-albumin: 60% of plasma proteins, produced by livers; main contributor to osmotic pressure
-globulins: 36% of plasma proteins
-alpha, beta: produced by liver, most are transport proteins that bind to lipids, metal ions, and fat soluble vitamins
-gamma: antibodies released by plasma cells during immune response
-fibrogen: 4% of plasma proteins; produced by liver; forms fibrin threads of blood clot

Other substances found in blood

-nonprotein nitrogenous substances: by products of cellular metabolism such as urea, uric acid, creatinine, and ammonium salts
-nutrients (organic): materials absorbed from digestive tract and transported for use throughout body; include glucose and other simple carbohydrates, amino acids (digestion products of proteins), fatty acids, glycerol and triglycerides (fat products), cholesterol, and vitamins
- electrolytes: cations include sodium, potassium, calcium, magnesium; anions include chloride, phosphate, sulfate, and bicarbonate; help maintain plasma osmotic pressure and normal blood pH
-respiratory gases: oxygen and carbon dioxide; oxygen mostly bound to hemoglobin inside RBCs; carbon dioxide transported dissolved in plasma as bicarbonate ion or CO2, or bound to hemoglobin in RBCs.
-hormones: steroid and thyroid hormones carried by plasma proteins

Formed Elements: what are the three major types of formed elements and where are they made?

1. Red Blood Cells-cells that have expelled their organelles and nuclei (aka erythrocytes)
2. White blood cells- complete cells (aka leukocytes)
3. Platelets-fragments of megakaryocytes
-They are formed in the red bone marrow
What are the relative sizes of the formed elements?
-Red blood cells: about 7.5 Micrometers in diameter
-Leukocytes:
-granulocytes:
-neutrophil: 10-12 micrometers, eosinophil: 10-14 micrometers, basophil: 10-14 micrometers
-arganulocytes:
-lymphocyte: 5-17 micrometers, monocyte:14-24 micrometer
-platelets: 2-4 micrometers

physical characteristics of RBCs

-small cells, shaped like biconcave discs (flattened disks with concave centers), appear lighter in color at centers than their edges.

Why is the shape of RBCs important

-the spectrin net is deformable, giving erythrocytes flexibility to change shape as necessary-to twist, turn and become cup shaped as they are carried passively through capillaries with diameters smaller than themselves, and then to resume their biconcave shape
-its small size and biconcave shape provide a huge surface area relative to volume (about 30% more surface area than comparable spherical cells). the biconcave disc shape is ideally suited for gas exchange because no point within the cytoplasm is far from the surface.

What is the compostition of the RBC (what is inside it)

-mature erythrocytes are bound by a plasma membrane but lack a nucleus and have no organelles. they are little more than "bags" of hemoglobin (the RBC protein that functions in gas transport). other proteins are present such as antioxidant enzymes that rid the body of harmful oxygen radicals, but most function mainly to maintain the plasma membrane or promote changes in RBC shape. spectrin- protein that maintains biconcave structure
-97% hemoglobin the molecule that binds to and transports respiratory gases

How does the number of RBCs contribute to the overall physical characteristics of the plasma? (What happens when there are too many or too few?)

When there are too many RBCs the viscosity of the blood becomes too thick and is harder to flow, and when there are too few the blood is thin and flows too rapidly.

Which of the factors matter in a transfusion to an Rh- person?

Person who is Rh- should only recieve Rh- blood
Receiving antibodies, giving antigens

Which factors matter in a transfusion to an Rh+ person?

Person who is Rh+ should only recieve Rh- or Rh+ blood
Receiving antibodies, giving antigens

If an Rh- person is exposed to Rh+ blood for the first time, what will happen to the Rh- person?

the immune system becomes sensitized and begins producing anti-Rh antibodies against the foreign antigen soon after the transfusion. hemolysis does not occur after the first such transfusion because it takes time for the body to react and start making antibodies.

If the same person is exposed to Rh+ blood again, what will happen to the Rh- person?
the second time and every time after a typical transfusion reaction occurs in which the recipient's antibodies attack and rupture the donor RBC's.

If this person (Rh-) is a mother with a Rh+ fetus, what could the mother be administered and how would it protect her and her fetus?

The mother could be administered RhoGAM which is a serum containing anti-Rh agglutins. bu agglutinating the Rh factor, it blocks the mother's immune response and prevents her sensitization.

Why is agglutination during a transfusion or in pregnancy a problem?

the moms antibodies will cross through the placenta and destroy the babys RBCs, producing a condition known as hemolytic disease of the newborn or erythroblastosis fetalis. the baby becomes anemic and hypoxic, brain damage and death can result in severe cases.

When there is excessive bleeding, leading to a decrease in the volume of blood, is restoration of volume or oxygen carrying capacity more of an immediate concern?

blood volume must be replaced immediately to restore adequate circulation.

How is excessive bleeding, leading to a decrease in the volume of blood dealt with?

replacing blood volume consists of replacing that isotonic salt solution. normal saline or a multiple electrolyte solution that mimics the electrolyte composition of plasma are the preferred choices

correct definition of anemia?

a condition in which the blood has abnormally low oxygen carrying capacity.

2 specific factors that would cause anemia due to insufficient erythrocytes

1. insufficient number of red blood cells: conditions that reduce the red blood cell count include blood loss, excessive RBC destruction, and bone marrow failure.
-hemmorrhagic anemias: result from blood loss. in acute hemorrhagic anemia, blood loss is rapid (stab wound), it is treated by blood replacement. slight but pesistent blood loss (hemorrhoids or bleeding ulcer) causes chronic hemorrhagic anemia. once the promary problem is resolved, normal erythropoietic mechanisms replace the deficient blood cells
-hemolytic anemias: erythrocytes rupture, or lyse, prematurely. hemoglobin abnormalities, transfusion of mismatched blood, and certain bacterial and parasitic infections are possible causes.
-aplastic anemia: may result from destruction or inhibition of the red marrow by certain drugs and chemicals, ionizing radiation, or viruses. in most cases, cause is unknown. because bone marrow destruction impairs formation of all formed elements, anemia is just one if its signs. defects in blood clotting and immunity are also present.

What causes anemia due to low hemoglobin content?

low hemoglobin content: when hemoglobin molecules are normal, but erythrocytes contain fewer than the usual number, a nutritional anemia is always suspected:
-iron deficiency anermia: generally a secondary result of hemmorrhagic anermias, but it also results from inadequate intake of iron containing food and impared iron absorption. iron treatment is available.
-athletes anermia: athletes that exercise vigorously, their blood colume expands and can increase by as much as 35% over time. since this increased volume effectively ilutes the blood components, a test for the iron content of the blood at such times would indicate iron deficiency anemia. blood components return to physiological levels within a week or so after the athlete resumes a normal level of activity.
-pernicious anemia: due to deficiency of vitam B12. intrinsic factor is deficient and since it is needed for B12 to be avsorbed by intestinal cells, B12 cells become insufficient

What causes anemia due to abnormal hemoglobin?

abornal hemoglobin: production of abnormal hemoglobin usually has a genetic basis.
-thalassemias: typically seen in people of mediterranean ancestry (greeks and italians). one of the globin chains is absent or faulty, and the erythrocytes are thin, delicate, and deficient in hemoglobin.
-sickle cell anemia: the havoc caused by the abnormal hemoglobin, hemoglobin S (HbS), results from a change in just one of the 146 amino acids in a beta chain of the globin molecule. this alteration causes the beta chains to link together under low ozyfen conditions, forming stiff rods so that the hemoglobin S becomes spiky and sharp. this causes the red blood cells to become crescent shaped when they unload the oxygen molecules or when the oxygen content of the blood is lower than normal (vigorous exercise or other activities) these shaped erythrocytes rupture easily and dam up small blood vessels which leaves the victim gasping for air and in extreme pain.

Po;ycythemia can be caused by increased levels of EPO, being at high altitudes or blood doping. Having more blood cells provides greater oxygen carrying capacity, so why can it be a problem for the body?

It increases blood viscosity (the blood becomes thicker) and it makes it harder for the heart to pump.

Name 3 differences (anatomical and/or functional) between erythrocytes and leukocytes.

-3 differences between erythrocytes and leukocytes
1. leukocytes have nucleus, erythrocytes are anucleate
2. leukocytes are spherical, erythrocytes are biconcave
3. There are more erythrocytes in the blood than leukocytes

Red blood cells are located in blood vessels. While there are some white blood cells in the blood vessels, where are most white blood cells found?

-Most of the WBC are found: able to slip out of capillary vessels (diapedesis) and the circulatory system is simply their means of transport to areas of the body where they where they are needed to mount inflammatory responses

When we say that white blood cells are attracted to a site of injury or information, they are responding to chemical signals left by the damaged tissue and other WBCs. What specific name is given to movement of white blood cells towards chemical signals?

Positive Chemotaxis

When white blood cells move, they have ameboid movement. When this movement is between endothelial cells of the blood vessels, the movement is called...

Nitric oxide and prostacyclin

There are 5 basic types of WBCs (leukocytes). Name each type of WBC, give a prominent physical characteristic, explain what its main function is, and indicate if it phagocytizes.

5 leukocytes
1. neutrophils: nucleus is multi lobed, function is to phagocytize bacteria
2. eosinophils: nucleus is bilobed, red cytoplasm granules, function is to kill parasitic worms and has a complex role in allergy and asthma, it does phagocytize
3. basophils: nucleus is bilobed, large purple/black granules, function is to release histamine and other mediators of inflammation, contains heparin (an anticoagulant), acts as a vasodilator and attracts other WBCs to inflamed sites, does not phagocytize
4. lymphocytes: nucleus is spherical or indented, pale blue cytoplasm, function is to mount immune responses by direct cell attack or via antibodies,does not phagocytize
5. monocytes: nucleus U or kidney shaped, grey, blue cytoplasm, function is phagocytosis-develop into macrophages in the tissues, does phagocytize

To remember the prevalence of WBCs in the blood, what sentence is useful to remember?

NEVER LET MONKEYS EAT BANANAS -most common to least common in blood

The functions of the white blood cells can be remembered by the acronym "DAR". D=defend against pathogens. What do the A and R represent?

Attack abnormal cells, remove toxins and waste

The acronym "MEN" represents the phagocytic cells. What cells are phagocytic?

Monocytes, Eosinophils, Neutrophils (M.E.N.) -phagocytic

Basophils are a type of white blood cell that has granules that contain histamine which acts as a vasodilator (makes blood vessels dialate) and attracts white blood cells. There is another cell type, not derived from the hemocytoblast stem cells, that has similar functions. What is the name of this cell type?

eosinophil

Lymphocytes differentiate into 3 separate "specialties". T lymphocytes develop in the thymus , can become cytotoxic cells (killing infected cells) and attacking Tumors. B lymphocytes and NK cells develop/mature in the bone marrow. What will B cell (derivatives-plasma cells, derived from B lymphocytes are the actual cells) produce in response to an infection?

Antibodies

What is the major role of NK (Natural Killer) cells.

Lyse - kills cancer cells and virus infected body cells before the adaptive immune system is activated.

B and T lymphocytes are the major components of specific immunity. NK cells and the other white blood cells are the major components of the what immunity?

innate immunity

When monocytes leave the blood vessels, what do they become?

Macrophages - actively phagocytic and are crucial in body's defenses against viruses, bacertial parasites, and chronic infection

What cell type is the most active and sturdy phagocyte?

neutrophils

When there is an infection and the white blood cells respond, what type of dead leukocyte is a part of the pus?

Neutrophils

Hemacytoblasts are stem cells for what cell types?

Hemocytoblast -> promegakaryocyte [megakaryoblast -> megakaryocyte] -> Platelets

Myelod stem calls give rise to what type(s) of formed element(s)?

Eosinophils, Basophils, Neutrophils, Monocytes

Lymphoid stem cells give rise to what type(s) of formed element(s)?

Lymphocytes

Megakaryoblasts give rise to what formed element(s)?

megakaryocyte -> platelets

What does the suffix "cytosis" indicate?

More than the usual number of cells

If you had erythrocytosis, what would that mean?

an excess number of erythrocytes (red blood cells)

What does the suffix "penia" mean?

lacking or deficiency

If someone had leucopenia, what would that mean? what causes it?

decrease number of white blood cell. it is drug induced

Leukemia and leukocytosis both are a condition in which there are too many white blood cells? How do they differ (be sure to address the cause)?

Leukocytosis is a high wbc count and it is a normal response to bacterial or viral invasion. Leukemia is too many white blood cells because the bone marrow is totally occupied with cancerous leukocytes.

Distinguish between a thrombus and an embolus. Which one poses a greater risk to health?

A thrombus is a clot that develops and persists in an unbroken blood vessel. if the thrombus is large enough, it may block circulation to the cells beyond the occlusion and lead to death of those tissues. for example, if the blockage occurs in the coronary circulation of the heart, the consequences may be death. an embolus is what a thrombus becomes when it breaks away from the vessel wall and floats freely in the blood stream. it usually is no problem until it encounters a blood vessel too narrow for it to pass through, which it then becomes an embolism, obstructing the vessel. for example, emboli that get trapped in lungs dangerously impair the ability of the body to obtain oxygen. a cerebral embolism may cause a stroke.

Excessive bleeding can occur because of a decrease in platelets as well as an increase in platelets. How can this occur? What is the name of each condition?

Thrombocytopenia: platelets are deficient. causes spontaneous bleeding from small blood vessels all over the body. even normal movements lead to widespread hemmorrhage, evidenced by many small purple dots caled petechiae on the skin. it can arise from any condition that suppresses or destroys the red bone marrow, such as bone marrow malignancy, exposure to ionizing radiation, or certain drugs.
Diseminated intravascular coagulation involved both widespread clotting and severe bleeding. results from septicemia or incompatible blood transfusions.

What is hemophilia?

Hemophilia refers to several different hereditary bleeding disorders that have similar signs and symptoms.

Hemophilia C, with a defect in the gene that codes for Factor XI is recessive, and is not sex linked. If both the mother and the father have a mutated gene and a normal gene for Factor XI, if they have 4 children what is the chance that one of them will display abnormal coagulation?

50%

Why might problems with the liver lead to problems with clotting?

when the liver is unable to synthesize its usual supply of procoagulants, abnormal, and often severe, bleeding occurs. the causes can range from an easily resolved vitamin K deficiency to nearly total impairment of liver function (as in hepatitis or cirrhosis).

Why are Calcium and Vitamin K important in clotting?

Vitamin K is not directly involved, but associated with forming the factors
Calcium is a necessary cofactor for binding. Low calcium means bad clotting.

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