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84 Cards in this Set
- Front
- Back
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What do RBCs (erythrocytes) do?
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Transport hemoglobin
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What do RBC's contain?
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Contain carbonic anhydrase:
Catalyzes the reaction between CO2 and H20 H2CO3 allowing the blood to transport CO2 in the form of bicarbonate ion (HCO3-) Acid-base buffer |
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What is the shape of RBCs?
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Are biconcave discs
Shape can change as the cells squeeze through capillaries |
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Average number of red blood cells per cubic millimeter
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Males = 5.2 x 106 (±300,000)
Females = 4.7 x 106 ((±300,000) |
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In terms of RBCs, what can they do?
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Have the ability to concentrate hgb in the cell fluid up to about 34 grams per 100 milliliters of cells
Each gram of hgb is capable of combining with 1.34 milliliters of O2 |
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Where are RBC's produced?
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Produced in the bone marrow
During fetal life produced in the liver, spleen, lymph nodes During the last month of gestation and after birth RBCs are produced in the bone marrow Bone marrow of all bones produces RBCs until the individual is 5 years old After 20 years of age RBCs produced in the marrow of the vertebrae, sternum, ribs and ilia |
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All blood cells derived from where? (Including RBCs and WBCs)
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All blood cells derived from the pluripotential hematopoietic stem cell (PHSC)
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The intermediate stage cells are what kinds of cells?
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The intermediate stage cells are committed stem cells (CFU-E, CFU-GM,CFU-M)
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Growth inducers do what?
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Growth inducers control reproduction and growth of the different stem cells, i.e. interleukcin-3
Both growth inducers and differentiation inducers are proteins |
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First RBC in the series is what?
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First RBC in the series is a proerythroblast
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what is derived from the proerythroblast?
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From proerythroblast is derived the basophil erythroblast
Stain with basic dyes, have accumulated very little hemoglobin |
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From basophil erythroblast, what is derived?
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From basophil erythroblast is derived the reticulocyte
Still has small amount of basic staining material (remnants of golgi apparatus, mitochondria, etc) During reticulocyte stage the cell passes from the bone marrow to the blood capillaries by diapedesis (squeezing through the pores of the capillary membrane) |
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What comes from the reticulocyte?
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From the reticulocyte comes the mature erythrocyte
Does not have basophilic material Does not have nucleus |
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What is RBC production regulated by?
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Tissue Oxygenation
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What does decreased tissue oxygenation cause?
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Decreased tissue oxygenation causes an increased rate of production of RBC
Anemia, high altitudes, poor blood flow (cardiac failure), pulmonary disease Erythropoietin enhances RBC production In the absence of erythropoietin hypoxia has little or no effect in stimulation of RBC production |
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In normal individual what percentage of erythropoietin is formed in the kidneys and what percentage is formed in the liver
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In normal individual 90% of erythropoietin is formed in the kidneys and 10% is formed in the liver
Is why individual becomes anemic with renal disease Norepinephrine, epinephrine and several prostaglandins stimulate erythropoietin production |
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Erythropoietin stimulates the production of what?
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proerythroblasts
After proerythroblasts are formed erythropoietin accelerates the rate of passing through the different erythroblastic stages |
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The erythropoietic cells of the bone marrow are some of the most rapidly growing and reproducing cells in the body.
Vitamin B12 and folic acid are required for the maturation of RBC What is essential for the synthesis of DNA (are required for the formation of thymidine triphosphate) |
Vitamin B12 and folic acid are required for the maturation of RBC
Are essential for the synthesis of DNA (are required for the formation of thymidine triphosphate) |
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What happens wit maturation failure?
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Failure to absorb Vitamin B12 from the GI tract
Pernicious anemia – have atrophic gastric mucosa which fails to produce normal gastric secretions Parietal cells secrete decreased intrinsic factor The intrinsic factor binds with Vit B12 and makes it available for absorption by the gut |
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Where is Vitamin B-12 stored?
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Once it is absorbed from the gut it is stored in the liver
The liver slowly releases Vit B12 for use by the bone marrow The minimum amount of Vit B12 required daily to maintain normal RBC maturation is 1-3mg Liver stores 1000 times the daily requirement 3-4 years of defective Vit B12 absorption is necessary to cause maturation failure anemia Individuals with sprue often have difficulty absorbing both Vit B12and folic acid |
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Discuss synthesis of hemoglobin.
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Synthesis begins in the proerythroblasts and continues into the reticulocyte stage
Succinyl CoA (a product of the Krebs cycle) combines with glycine and forms a pyrrole molecule Four pyrroles combine and form protoporphyrin IX which combines with iron and forms the hemoglobin chain Each heme molecule combines with a globulin and forms a hemoglobin chain |
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What is the hemoglobin molecule formed by?
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Four hemoglobin chains combine to form the hemoglobin molecule
Each hemoglobin chain has an atom of iron therefore, 4 molecules of oxygen can be transported by each hemoglobin molecule |
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Discuss the hemoglobin chain
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Depending on the amino acid composition of the chain the hemoglobin can vary
Alpha, beta, gamma and delta chains Hemoglobin A is a combination of two alpha chains and two beta chains Sickle cell hemoglobin is due to the substitution of valine for glutamic acid in each of the two beta chains |
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What might happen to the hemoglobin chain in sickle cell?
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When sickle cell hgb is exposed to low oxygen it forms crystal sin the RBC and these make it almost impossible for the RBC to pass through small capillaries.
Moreover, the spiked end of the crystals are likely to rupture the cell membranes which leads to sickle cell anemia |
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What is the total quantity of iron in the body and what is the composition of it?
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Total quantity of iron in the body is 4-5 grams 65% in hgb, 4% in myoglobin, 1% in various heme compounds, 15-30% is stored in the form of ferritin, 0.1% is combined with transferrin in the blood plasma
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Iron is absorbed from where and is deposited where?
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Iron is absorbed from the small intestine and combines with apotransferrin in the plasma and forms transferrin
Iron is bound loosely and can be released to any tissue cell Excess iron in the blood is deposited in the liver hepatocytes and to a lesser degree in the reticuloendothelial cells of the bone marrow |
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How is ferritin and hemosideran formed?
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In the cell iron combines with apoferritin to form ferritin
If the total quantity of iron in the body exceeds the amount that the apoferritin storage pool can accommodate, the iron forms an extremely insoluble form called hemosiderin. |
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What happens if the plasma iron level is low?
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If the plasma iron level is low some of the iron in the ferritin storage pool is removed and transported by transferrin in the plasma to areas where it is needed
The transferrin molecule binds strongly with receptors in the cell membranes of erythroblasts in the bone marrow. It enters the erythroblasts by endocytosis and the transferrin delivers the iron directly to the mitochondria Heme is synthesized in the mitochrondria |
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What happens if an individual does not have adequate quantities of transferrin in their blood?
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it can cause hypochromic anemia (RBC that do not contain enough hemoglobin).
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What happens when RBC are destroyed?
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When RBC are destroyed, the hgb is released is ingested by monocyte macrophage cells and the iron is stored in the ferritin pool until it is needed for the formation of new hgb
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Describe the life span of RBCs
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RBC circulate an average of 120 days
As they age the metabolic systems become less active and the RBC become more fragile When the RBC becomes more fragile it can rupture during passage through some tight spots of the circulation Many self-destruct in the spleen |
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Discuss destruction of RBCs
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When RBC ruptures hgb is released and phagocytized by macrophages – especially the Kupfer cells in the liver and macrophages of the spleen and bone marrow
Iron is released into the blood where it is carried by transferrin To the bone marrow for production of new RBC To the liver for storage as ferritin The porphyrin portion is converted by the macrophages into bilirubin which is released into the blood, passed through the liver and secreted into the bile. |
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Describe anemia in general
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Anemias – decreased hgb in the blood (too few RBC, or too little hgb in the cells)
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What is blood loss anemia?
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Blood loss anemia
In chronic blood loss RBC are produced, which are smaller than normal and contain too little hgb (microcytic hypochromic anemia) |
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What is aplastic anemia?
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Aplastic anemia – bone marrow aplasia
Lack of functioning bone marrow Gamma radiation X-ray treatments Chemicals and drugs |
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What is megaloblastic anemia?
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RBC grow too large and have odd shapes (fragile membrane)
Decreased Vit B12 or decreased folic acid or decreased intrinsic factor Atrophy of stomach mucosa (pernicious anemia) Loss of entire stomach – gastrectomy Intestinal sprue |
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What is hemolytic anemia?
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abnormalities of RBC make the cell fragile
Hereditary spherocytosis – RBC are small and spherical not biconcave discs Can’t withstand compression forces |
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Describe Sickle cell anemia
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Sickle cell – RBC have hgb-S – contain faulty beta chains
Decreased O2 causes hgb-S to precipitate into long crystals inside the RBC The crystals elongate the cell (sickle) The crystals make the cell fragile Sickle cell crisis – viscous circle decreased O2 sickling ruptured RBC further decreased O2 more sickling and increased RBC destruction further decreased O2 etc. |
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What is erythroblastosis fetalis?
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Erythroblastosis fetalis – Rh-positive RBC in the fetus are attacked by antibodies from an Rh-negative mother
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What are the effects of anemia?
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Decreased cells viscosity decreased resistance to blood flow in peripheral tissues increased quantities of blood flow through tissues increased return to the heart increased cardiac output
Decreased transport of O2 peripheral vasodilation further increase in return to heart increased output to higher level During states of increased tissue demand for O2 (exercise) extreme tissue hypoxia occurs and acute cardiac failure results One of the major effects is greatly increased cardiac output and increased pumping workload in the heart |
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What is Secondary polycythemia?
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Caused whenever the tissues become hypoxic because of decreased O2 in the breathed air (high altitudes, cardiac failure)
The blood-forming organs produce large quantities of extra RBC Physiologic polycythemia occurs in individuals who live at high altitudes |
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What is polycythemia vera?
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Polycythemia vera
A pathological condition caused by a genetic aberration in the hemocytoblastic cells that produce the RBC Increased HCT Increased total blood volume Vascular system becomes engorged Increased viscosity capillaries becoming plugged |
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What are the effects of polycythemia?
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Sluggish blood flow
Decreased rate of return to heart due to increased viscosity offset by increased rate of return (increased venous return) due to increased blood volume Ruddy complexion with a bluish tint |
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Where are WBCs formed and where are they transported?
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Formed partially in the bone marrow
Granulocytes and monocytes Few lymphocytes Formed partially in the lymph tissue Lymphocytes Plasma cells After formation, are transported via the blood stream to areas of the body where they are needed |
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What are the six types of leukocytes?
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Polymorphonuclear neutrophils
Polymorphonuclear eosinophils Polymorphonuclear basophils Monocytes Lymphocytes Plasma cells |
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Describe some specifics about the 6 kinds of leukocytes
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The first 3 types are the polys or the granulocytes
The granulocytes and monocytes protect from invading organisms by phagocytosis The lymphocytes and plasma cells function with the immune system Platelets are fragments of megakaryocyte and their function is to activate the blood clotting mechanism |
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What are the 2 lineages of WBCs?
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Myelocytic from the myeloblast
Lymphocytic from the lymphoblast |
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When released from the bone marrow, do granulocytes have a long or short life span?
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Granulocytes once released from the bone marrow have a short life span
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Discuss the life span of the granulocytes
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4-8 hrs in blood (transit time)
4-5 days in tissues where needed The total life span is shortened to 3-4 hrs in times of serious tissue infection Granulocytes proceed more rapidly to the infected area and during the course of performing their function (phagocytosis) are destroyed. |
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Whats the life span of monocytes?
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Monocytes life span
10-20 hrs in the blood Wander through capillary membranes to enter the tissue Once in the tissues the monocytes swell and become tissue macrophages In this form can live for months unless they are destroyed performing phagocytosis These tissues macrophages are the basis of the tissue macrophage system. |
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Where do lymphocytes enter the circultory system? And where do they go?
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Lymphocytes enter the circulatory system with the lymph drainage
After a few hours they pass out of the blood back into the tissues by diapedesis This process is repeated again and again Lymphocytes have a lifespan of weeks to months Longevity depends on the body’s need |
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Platelets are replaced how often?
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Every 10 days.
30,000 platelets are formed each day for each microliter of blood |
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What do Neutrophils and tissue macrophages do?
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attack and destroy invading bacteria, viruses, etc
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By which process do Neutrophils and monocytes squeeze through the pores of the capillaries?
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diapedesis
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How do Neutrophils and macrophages move through the tissues?
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by ameboid motion
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True or false: Different chemical substances in the tissue can attract neutrophils and macrophages
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true
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Chemotaxis caused by products in inflamed tissue. Describe some of those products
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Bacterial or viral toxins
Degenerative products of the inflamed tissues Products of the complement system Reaction products caused by plasma clotting in the inflamed area |
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True or False: Chemotaxis depends on the concentration gradient of the chemotatic substance
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True
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Define Phagocytosis
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cellular ingestion – occurrence depends on 3 selective processes
Most natural structures in tissue have smooth surfaces which resist phagocytosis Phagocytosis occurrence is increased if surface is rough Most natural substances in the body have protein coats that repel phagocytes Most dead tissue and foreign particles have no protective coat and are thus subject to phagocytosis The immune system develops antibodies against bacteria, etc The antibodies adhere to the bacterial membranes and make the bacteria especially susceptible to phagocytosis Antibody molecule combines with the C3 product attaches to receptors on the phagocyte membrane and thereby initiates phagocytosis The selection and consequent phagocytosis is opsonization |
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A single neutrophil can usually phagocytize how many bacteria?
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3-20 bacteria
Project pseudopods which engulf the particle and form a phagocytic vesicle (phagosome) |
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Phagocytosis – cellular ingestion – occurrence depends on 3 selective processes:
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Most natural structures in tissue have smooth surfaces which resist phagocytosis
Phagocytosis occurrence is increased if surface is rough Most natural substances in the body have protein coats that repel phagocytes Most dead tissue and foreign particles have no protective coat and are thus subject to phagocytosis |
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The immune system develops antibodies against bacteria, etc
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The antibodies adhere to the bacterial membranes and make the bacteria especially susceptible to phagocytosis
Antibody molecule combines with the C3 product attaches to receptors on the phagocyte membrane and thereby initiates phagocytosis The selection and consequent phagocytosis is opsonization A single neutrophil can usually phagocytize 3-20 bacteria Project pseudopods which engulf the particle and form a phagocytic vesicle (phagosome) Macrophages are more powerful phagocytes than are the neutrophils Can phagocytize up to 100 bacteria Can engulf large particles Whole red blood cells or malarial parasites After digesting particles can extrude the residual products and survive and function for many more months |
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Neutrophils and macrophages contain bactericidal agents (peroxiome)
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Oxidizing agents
Superoxide (O2-) H202 (hydrogen peroxide) OH- Myeloperoxidase – catalyzes the reaction between O2O2 and CL- to form hypochlorite Hypochlorite is very bacteriocidal |
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What is reticuloendothelial systems?
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The combination of monocytes, mobile macrophages, fixed tissue macrophages, and a few specialized cells in the bone marrow, spleen, and lymph nodes
Is also the monocyte – macrophage system |
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What are Histiocytes?
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local tissue macrophages in the skin or subcutaneous tissue
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What are lymph nodes?
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a network of sinuses lined by tissue macrophages
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True or False: Large numbers of tissue macrophages are present as integral components of the alveolar walls?
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True
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The sinusoids of the liver are lined with what?
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The sinusoids of the liver are lined with tissue macrophages termed Kupffer cells
This particulate filtration system is so effective that almost none of the bacteria from the GI tract is successful in passing from the portal blood into the general circulation. |
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If an invading organism succeeds in entering the general circulation, what organs deal with it?
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If an invading organism succeeds in entering the general circulation the tissue macrophage system of the spleen and bone marrow is used.
In these tissues macrophages have become entrapped by the reticular meshwork of the two organs |
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What is the red pulp lined with?
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The trabeculae of the red pulp are lined with macrophages as are the venous sinuses
This passage of blood through the cords of red pulp allows the phagocytosis of unwanted debris in the blood Old and abnormal RBC |
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Inflammation happens when?
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Multiple substances released by injured tissue and cause secondary changes in the surrounding uninjured tissue
Characterized by Vasodilation of the local blood vessels Consequent excess local blood flow Increased permeability of the capillaries Allows leakage of large quantities of fluid into the interstitial spaces Clotting of fluid in the interstitial spaces Due to fibrinogen and other proteins leaking from the capillaries Migration of granulocytes and monocytes into the tissue Swelling of the tissue cells |
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Tissue changes are due to what?
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histamine, bradykinin, serotonin, prostaglandins, products of the complement system, products of the blood clotting systems, lymphokines (released by sensitized T cells)
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What is one of the first results of inflammation...and what is the intensity of the inflammatory process due to?
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One of the first results of inflammation, is “walling off” the injured area.
Tissue spaces and lymphatics are blocked by fibrinogen clots Fluid barely flows through these areas Delays the spread of bacteria or toxic products Intensity of the inflammatory process is usually proportional to the degree of tissue injury |
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what is the first line of defense?
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Tissue macrophage is first line defense
Within minutes after inflammation begins the macrophages already present begin phagocytosis and enlarge Sesile macrophages become mobile These processes occupy the first hour Then, Neutrophils from the blood travel to and invade the inflamed area (1-1+ hrs) Is caused by inflamed tissue products Alter the inside of the capillary endothelium and cause neutrophils to adhere to the surface (margination) Alter the capillary so that neutrophils may enter the tissue space by diapedesis Chemotaxis of the neutrophils to the inflamed area End result is that during the first several hours after tissue injury or damage the area is supplied with neutrophils |
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Neutrophilia occurs when?
What is the 3rd line of defense? |
Neutrophilia occurs after the first few hours after the onset of acute, severe inflammation
Neutrophil count increases from 4-5 thousand to 15-25 thousand per microliter Occurs due to inflammation products acting on the bone marrow and causes the stored neutrophils to be released Third line of defense is a second macrophage invasion of the area Monocytes from the blood enter the tissue and enlarge and become macrophages Number of monocytes circulating and stored in the marrow is small (more time required: several days) Monocytes require 8 hrs to mature to macrophages After several days to weeks macrophages dominate the inflamed area |
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What is the 4th line of defense?
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Fourth line of defense is increased production of granulocytes and monocytes by the bone marrow
Factors from activated macrophages in the inflamed area control the macrophage and neutrophil response |
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What is the cause of the increased production of both granulocytes and monocytes?
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The cause of the increased production of both granulocytes and monocytes is GM-CSF (granulocyte-monocyte colony-stimulating factor)
G-CSF and M-CSF stimulate granulocytes and monocyte respectively TNF (tumor necrosis Factor and IL-1 (Interleukin-1) in combination with the colony stimulating factors provides a powerful feedback mechanism |
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Pus formation occurs when?
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Pus formation occurs after neutrophils and macrophages phagocytize – it is dead neutrophils and macrophages, necrotic tissue and tissue fluid
After suppression of the infection, the dead cells and necrotic tissue autolyze over a period of days |
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Discuss eosiniphils
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Eosinophils – normally are 2% of the blood leukocytes
Are weak phagocytes Are produced in large numbers in individuals with a parasite infection Eosinophils attach to parasites and release substances that kill them Most parasites are too large to be phagocytized Eosinophils release from their granules (modified lysosomes) Hydrolytic enzymes Highly reactive forms of oxygen Highly larvacidal polypeptide (major basic protein) Eosinophils moreover have a propensity to accumulate in tissues in which allergic reactions occur Most cells and basophils participate in allergic reactions and release eosinophil chemotactic factor The eosinophils are believed to detoxify some of the inflammation-inducing substances released by mast cells and basophils Eosinophils are also thought to phagocytize and destroy allergen-antibody complexes This would prevent excess spread of the local inflammatory process |
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Discuss some properties of basophils
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Are similar to most cells
Both liberate heparin into the blood Both release histamine, bradykinin, and serotonin Mainly released by mast cells |
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Do eosinophils or basophils play a role in allergic reactions?
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Both play role in allergic reactions
IgE has a propensity to become attached to mast cells and basophils Then when the antigen reacts with the antibody the resultant antigen-antibody complex causes the mast cell or basophil to rupture and release histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis and lysosomal enzymes Cause local vascular and tissue reactions that cause many of the allergic manifestations |
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What is Leukopenia?
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Leukopenia – bone marrow produces too few white blood cells
Leaves body unprotected – allows invasion by everpresent bacteria Within 2 days after bone marrow stops producing WBC ulcers may appear in mouth, colon, may develop severe respiratory infection Without treatment, death often occurs in less than a week after acute total leukopenia begins |
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What is leukemia?
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Uncontrolled production of WBC
Many abnormal WBC – undifferentiated and bizarre May be lymphocytes or myelogenous If cells differentiated: eosinophetic, basophilic, neutrophilic, may be chronic The more undifferentiated usually means more acute often leading to death |
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Describe some of the effects of leukemia
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Effects of leukemia
Metastatic growth of leukemic cells May invade surrounding bone and cause pain and weakness of the bone leading to fractures Almost all leukemias eventually spread to spleen, lymph nodes and liver Development of infection Anemia Bleeding due to thrombocytopenia Metabolic starvation due to excessive use of metabolic substrates by the growing cancerous cells |
