Chapter 18 - Blood

Describe hemoglobin structure

-4 globular protein chains -2 alpha and 2 beta proteins -each protein chain conjugated to nonprotein heme group with iron ion in center -center portion reversibly binds oxygen and carbon

Describe the consequences of inappropriate coagulation

-arm or leg swelling on 1 side of the body -pain in the arm or leg where a blood clot is located -trouble breathing or chest pain when breathing -rapid heart beat -low oxygen levels

What does the blood regulate?

-bicarbonate buffers acids/bases -vasoconstriction and vasodilation for temperature changes -stabilize water balance

Hypoplastic anemia

-caused by a decline in erythropoiesis -about half of all cases of hypoplastic anemia are of unknown or hereditary cause, especially in adolescents and young adults *Potential consequences: -tissues are deprived of O2 (hypoxia/hypoxemia); shortness of breath, lethargy (lack of energy), tissue necrosis (tissue destruction) -reduced blood osmolarity (less cells = more fluid); edema- fluid leaves bloodstream & enters tissues -reduced blood viscosity- less blood flow resistance, heart beats faster, blood pressure drops -heart failure

Secondary polycythemia

-characterized by RBC counts as high as 6 to 8 million RBCs/µL -can result from dehydration because water is lost from the bloodstream while erythrocytes remain and become abnormally concentrated -smoking, air pollution, emphysema, high altitude, excessive aerobic exercise, or other factors that create a state of hypoxemia and stimulate erythropoietin secretion *Dangers are increased blood volume, pressure, and viscosity.

Aplastic anemia

-complete failure or destruction of the myeloid tissue produces -complete cessation of erythropoiesis: leads to grotesque tissue necrosis and blackening of the skin *Potential consequences: -tissues are deprived of O2 (hypoxia/hypoxemia); shortness of breath, lethargy (lack of energy), tissue necrosis (tissue destruction) -reduced blood osmolarity (less cells = more fluid); edema- fluid leaves bloodstream & enters tissues -reduced blood viscosity- less blood flow resistance, heart beats faster, blood pressure drops -heart failure

Chronic leukemia

-develops more slowly and may go undetected for many months; if untreated, the typical survival time is about 3 years -effects: normal cell % disrupted, patient subject to opportunistic infection, anemia & impaired clotting

Primary polycythemia

-due to cancer of the erythropoietic line of the red bone marrow -can result in an RBC count as high as 11 million RBCs/µL and a hematocrit as high as 80% *Dangers are increased blood volume, pressure, and viscosity. Blood volume can double in primary polycythemia and cause the circulatory system to become tremendously engorged. Blood viscosity may rise to three times normal. Circulation is poor, the capillaries are congested with viscous blood, and the heart is dangerously strained. Chronic (long-term) polycythemia can lead to embolism, stroke, or heart failure

Vascular spasms

-first hemostatic mechanisms -prompt constrict broken blood vessel, reducing hemorrhage

How does the blood protect?

-formed elements destroy pathogens -platelets plug holes in blood vessels -globulins help eliminate infections agents

Inadequate erythropoiesis/hemoglobin synthesis

-iron-deficiency anemia, characterized by small pale erythrocytes -usually caused by blood loss without getting enough dietary iron to compensate for it *Potential consequences: -tissues are deprived of O2 (hypoxia/hypoxemia); shortness of breath, lethargy (lack of energy), tissue necrosis (tissue destruction) -reduced blood osmolarity (less cells = more fluid); edema- fluid leaves bloodstream & enters tissues -reduced blood viscosity- less blood flow resistance, heart beats faster, blood pressure drops -heart failure

Coagulation

-last hemostatic mechanisms -conversion of plasma protein fibrinogen into insoluble fibrin threads to form framework of clot -includes intrinsic and extrinsic mechanisms

List the possible causes of hypoxemia in the body

-loss of blood -high altitudes -sedentary person starts exercise program

Describe the process of erythrocyte death & disposal

-membrane proteins deteriorate and become fragile -w/o nucleus, RBC cannot synthesize protein spectrin found in membrane -many get trapped in narrow vessels of spleen and are hemolyzed -kidneys can also split hemoglobin molecules to recyclable portions

Average hemoglobin concentration

-men: 13 to 18 g/dL -women: 12 to 16 g/dL

Average RBC count

-men: 4.6 to 6.2 million RBCs/µL -women: 4.2 to 5.4 million RBCs/µL

Average hematocrit

-men: 42% and 52% -women: 37% and 48%

Pernicious anemia

-occurs when stomach glands fail to produce intrinsic factor (necessary for B12 absorption) -autoimmune disease in which antibodies destroy stomach tissue; can also be hereditary *Potential consequences: -tissues are deprived of O2 (hypoxia/hypoxemia); shortness of breath, lethargy (lack of energy), tissue necrosis (tissue destruction) -reduced blood osmolarity (less cells = more fluid); edema- fluid leaves bloodstream & enters tissues -reduced blood viscosity- less blood flow resistance, heart beats faster, blood pressure drops -heart failure

What does blood transport?

-oxygen from lungs to tissues, carbon dioxide from tissues to lungs -hormones -urea to kidneys -nutrients

Platelet plug formation

-second hemostatic mechanisms -broken vessel exposes collagen and platelet pseudopods stick to damaged vessel and other platelets; pseudopods contract and draw walls of vessel together forming a platelet plug; platelets degranulate releasing a variety of substances; positive feedback cycle

Describe the functions of platelets

-secrete vasoconstrictors -form temporary platelet plugs -secrete procoagulants (clotting factors) -initiate the formation of a clot-dissolving enzyme -secrete chemicals that attract neutrophils and monocytes to sites of inflammation -internalize and destroy bacteria -secrete growth factors that stimulate mitosis in fibroblasts and smooth muscle and thereby help to maintain and repair blood vessels

Define fibrinolysis or dissolution of a clot

-small cascade of reactions with a positive feedback component -factor XII catalyzes the formation of a plasma enzyme kallikrein -kallikrein converts the inactive protein plasminogen into plasmin -thrombin also activates plasmin, and plasmin indirectly promotes the formation of more kallikrein, thus completing a positive feedback loop

What percentage of WBCs are basophils?

0%-1%

What percentage of WBCs are monocytes?

2%-8%

What percentage of WBCs are lymphocytes?

20%-40%

What percentage of plasma protein is globulin?

36%

What percentage of whole blood is erythrocytes?

37%-52% (average 45%)

What percentage of plasma protein is fibrinogen?

4%

What percentage of WBCs are neutrophils?

40%-70%

What percentage of whole blood is plasma?

47%-63% (average 55%)

What percentage of plasma protein is albumin?

60%

What percentage of plasma is water?

92%

Explain how hemostasis is a positive feedback cycle

As platelets aggregate, they undergo degranulation—the exocytosis of their cytoplasmic granules and release of factors that promote hemostasis. Among these are serotonin, a vasoconstrictor; adenosine diphosphate (ADP), which attracts more platelets to the area and stimulates their degranulation; and thromboxane A2, an eicosanoid that promotes platelet aggregation, degranulation, and vasoconstriction.

Explain erythrocyte homeostasis

Classic negative feedback. If the count should drop (for example, because of hemorrhaging), it may result in a state of hypoxemia (oxygen deficiency in the blood). The kidneys detect this and increase their EPO output. Three or four days later, the RBC count begins to rise and reverses the hypoxemia that started the process.

Conditions improved through erythropoiesis, leukopoiesis, or neither

Erythropoiesis: sickle cell disease, anemia, hemolysis, hemorrhage, hypoxia Leukopoiesis: leukopenia Neither: leukemia, hematology, primary and secondary polycythemia

List the major types of WBCs

Granulocytes: Neutrophils, Eosinophils, Basophils Agranulocytes: Lymphocytes, Monocytes

What are the components of the circulatory system?

Heart, blood vessels, and blood

Which of the following is the correct sequence in the breakdown of the non-iron portion of the heme?

Heme, biliverdin, bilirubin, conjugated bilirubin, bilirubin derivatives, feces and urine

Hemophilia

Hereditary diseases characterized by deficiencies of one factor or another; sex-linked, occurs predominantly in males (inherit it only from their mothers), The lack of factor VIII causes classical hemophilia (hemophilia A), which accounts for about 83% of cases. Lack of factor IX causes hemophilia B, which accounts for 15% of cases. Factors VIII and IX are therefore known as anti-hemophilic factors A and B. A rarer form called hemophilia C (factor XI deficiency) is autosomal and not sex-linked, so it occurs equally in both sexes.

Platelet repulsion

Method to prevent inappropriate coagulation where platelets do not adhere to the smooth prostacyclin-coated endothelium of healthy blood vessels.

Dilution

Method to prevent inappropriate coagulation where small amounts of thrombin form spontaneously in the plasma, but at normal rates of blood flow, the thrombin is diluted so quickly that a clot has little chance to form. If flow decreases, however, enough thrombin can accumulate to cause clotting. This can happen in circulatory shock, for example. When output from the heart is diminished and circulation slows down, widespread clotting throughout the circulatory system may occur.

Anticoagulants

Method to prevent inappropriate coagulation where thrombin formation is suppressed by anticoagulants that are present in the plasma. Antithrombin, secreted by the liver, deactivates thrombin before it can act on fibrinogen. Heparin, secreted by basophils and mast cells, interferes with the formation of prothrombin activator, blocks the action of thrombin on fibrinogen, and promotes the action of antithrombin. Heparin is given by injection to patients with abnormal clotting tendencies.

How are leeches used in medicine?

Preventing clots: -hirudin: first known anticoagulant discovered in the saliva of the medicinal leech; polypeptide that prevents clotting by inhibiting thrombin Dissolving formed clots: -hementin: produced by giant Amazon leech - -tissue plasminogen activator (TPA): works faster, is more specific, and now made by transgenic bacteria

How is the structure of erythrocytes related to function?

RBCs rely exclusively on anaerobic fermentation to produce ATP; cytoplasm consists mainly of 33% hemoglobin

T/F: Free bilirubin is transported by the blood to the liver.

True

T/F: Iron is transported in the blood by transferrin.

True

List some causes of disseminated intravascular coagulation (DIC)

Widespread clotting within unbroken vessels, limited to one organ or occurring throughout the body. Usually triggered by septicemia (bacteria in bloodstream) but also occurs when blood circulation slows markedly (as in cardiac arrest). Marked by widespread hemorrhaging, congestion of the vessels with clotted blood, and tissue necrosis in blood-deprived organs.

Adults have _____L of blood

Women: 4-5L Men: 5-6L

What are the major plasma proteins?

albumins, fibrinogen, globulins

Embolus

any abnormal traveling object in the bloodstream, such as agglutinated bacteria or blood cells, a blood clot, or an air bubble

Acute leukemia

appears suddenly, progresses rapidly, and causes death within a few months if it is not treated effects: normal cell % disrupted, patient subject to opportunistic infection, anemia & impaired clotting

In the breakdown of hemoglobin, the globin chains _________.

are broken down by macrophages into amino acids

Leukemia

cancer of hemopoietic tissue that produces high number of circulating leukocytes and their precursors effects: normal cell % disrupted, patient subject to opportunistic infection, anemia & impaired clotting

Sickle cell disease

cause by recessive allele that modifies the hemoglobin beta chain *Potential consequences: -tissues are deprived of O2 (hypoxia/hypoxemia); shortness of breath, lethargy (lack of energy), tissue necrosis (tissue destruction) -reduced blood osmolarity (less cells = more fluid); edema- fluid leaves bloodstream & enters tissues -reduced blood viscosity- less blood flow resistance, heart beats faster, blood pressure drops -heart failure

Thrombus

clot that forms in a blood vessel or heart chamber; may break free and travel in the bloodstream as a thromboembolus

What is the function of fibrinogen?

clotting, soluble precursor of fibrin

Describe the function of prostacyclin

coats endothelium making it smooth, inhibits platelet activation (platelet repellant), and is also an effective vasodilaton

What is the function of albumin?

colloid osmotic pressure, major contributor to blood viscosity, transports lipids, hormones, calcium, and other solutes, buffers blood pH

What kind of tissue is blood?

connective tissue because it has a matrix; more matrix vs cells (plasma in blood is at higher proportion than cells: 55% liquid, 45% actual cells)

What is the function of tissue plasminogen activator (TPA)?

converts plasminogen into the clot-dissolving enzyme plasmin, works faster, is more specific, and now made by transgenic bacteria

Thalassemia

deficiency or absence of alpha or beta hemoglobin *Potential consequences: -tissues are deprived of O2 (hypoxia/hypoxemia); shortness of breath, lethargy (lack of energy), tissue necrosis (tissue destruction) -reduced blood osmolarity (less cells = more fluid); edema- fluid leaves bloodstream & enters tissues -reduced blood viscosity- less blood flow resistance, heart beats faster, blood pressure drops -heart failure

Describe the structure of a typical erythrocyte

discoidal cell with a biconcave shape (thick rim and a thin sunken center); lack nucleus, mitochondria, and organelles

What is streptokinase?

enzyme made by streptococci bacteria, used to dissolve clots in coronary vessels, digests almost any protein

What does thrombin do?

enzyme that converts fibrinogen to fibrin to form a clot

What does plasmin do?

fibrin-dissolving enzyme that breaks up the clot

Thrombosis

formation or presence of a thrombus, abnormal clotting of blood in an unbroken blood vessel

Explain the process of erythropoiesis

hemopoietic stem cells, CFUs, erythroblasts, reticulocytes, erythrocytes -begins when a hemopoietic stem cell becomes an erythrocyte colony-forming unit, which has receptors for erythropoietin (hormone secreted by the kidneys) -EPO stimulates the ECFU to transform into an erythroblast (normoblast) -erythroblasts multiply, build up a large cell population, and synthesize hemoglobin -nucleus shrivels and is discharged from the cell, now called a reticulocyte, named for a temporary network (reticulum) of ribosome clusters transcribing the cell's remaining mRNA (polyribosomes) -reticulocytes leave the bone marrow and enter the circulating blood; in a day or two, the last of the polyribosomes disintegrate and disappear, and the cell is a mature erythrocyte

Leukocytosis

high WBC count (>10,000/uL) causes: infection, allergy, disease, dehydration, emotional disturbances

How does osmolarity affect the body?

if too high, bloodstream absorbs too much fluid from the tissues, thus causing hypertension and strain on the heart/arteries; if too low, the blood stream transfers fluid to the tissues causing edema and hypotension

Lymphoid leukemia

involves uncontrolled lymphocyte or monocyte production (acute or chronic) effects: normal cell % disrupted, patient subject to opportunistic infection, anemia & impaired clotting

What nutrients are required for erythropoiesis?

iron (key nutrient) folic acid vitamin B12 vitamin C copper

What percentage of whole blood is the buffy coat?

less than 1%

Leukopenia

low WBC count (<5000/uL) causes: radiation, poisons, infectious disease effects: elevated risk of infection

What is hemoglobin concentration?

measure of concentration of hemoglobin in a given volume of packed RBCs (hemoglobin/hematocrit)

What is hematocrit?

percentage of total volume that is cells, centrifuging blood forces formed elements to separate from plasma (light float to top, heavy sink bottom)

What are the components of blood?

plasma, RBC, WBC, platelets

Thrombocytopenia

platelet count below 100,000/mL causes include bone marrow destruction by radiation, drugs, poisons, or leukemia. Signs include small hemorrhagic spots in the skin or hematomas in response to minor trauma

Which is more abundant: WBCs or platelets?

platelets are the second most abundant formed elements, but are so small that they contribute even less than WBCs to the blood volume

What is the function of aspirin?

prevent clots by suppressing thromboxane A2

What is hemopoietic tissue?

produce formed elements (RBCs, WBCs, platelets); arise from hemopoietic stem cells (HSC) or pluripotent stem cells (PPSC)

What is myeloid hemopoiesis?

production of all seven formed elements in red bone marrow

What is lymphoid hemopoiesis?

production of lymphocytes in the lymphatic tissues and organs

How does viscosity affect the body?

protein deficiency can cause decreased viscosity causing blood to flow too easily, and excess causes blood to flow sluggishly; both lead to serious cardiovascular problems

where is hemopoietic tissue found?

red bone marrow and lymphatic tissues

Describe the structure of a platelet

small fragments (2 to 4 µm) of marrow cells called megakaryocytes complex internal structure that includes lysosomes, mitochondria, microtubules and microfilaments; granules filled with platelet secretions; and a system of channels called the open canalicular system, which opens onto the platelet surface; no nucleus

Explain the process of thrombopoiesis

some hemopoietic stem cells develop receptors for thrombopoietin and, under its influence, become megakaryoblasts megakaryocyte sprouts long tendrils called proplatelets which are sheared off by blood flow, and break up into platelets as they travel in the bloodstream and small vessels of the lungs

What is fibrin?

sticky, fibrous protein formed from fibrinogen in blood, tissue fluid, and lymph; forms matrix of blood clot

Define viscosity

the resistance to flow

What is the function of coumarin and warfarin?

they are vitamin K antagonists that prevent clots

Define osmolarity

total molar concentration of dissolved particles in 1 L of solution due to transfer of nutrients and wastes between the blood & tissue fluids (total molarity of dissolved particles that cannot pass through blood vessel wall)

What is the function of globulin?

transport and immune system defense functions

Functions of blood

transport, protection, regulation

Myeloid leukemia

uncontrolled granulocyte production (acute or chronic) effects: normal cell % disrupted, patient subject to opportunistic infection, anemia & impaired clotting

What happens to the blood if both the amount of erythrocytes and protein increases?

viscosity and osmolarity increase

List the components of plasma

water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and other compounds