Blood and Hematopoiesis
Rahul's Noteblog
Notes on Histology
Blood and Hematopoiesis
What is Blood?
• Blood is an extremely loose connective tissue specialized as a transportation vehicle.
• It does not contain a fibrillar component aside from fibrin. 5-6 liters per 150 lb.
• Diagnostic tool.
Function of Blood
1. Respiratory gas transport, oxygen and carbon dioxide.
2. Transport of:
a. Waste products.
b. Nutrients.
c. Hormones.
d. Antibodies.
e. Heat.
3. Transport route for cells associated with the immune system.
Blood Components Upon Centrifugation
• Plasma layer: Fluid component is plasma. from which interstitial fluid is derived.
• Primarily water 55% of total blood content without clotting proteins.
Plasma proteins
Albumins:
• Constitute the bulk of the proteins and bind such items as fatty acids thus serve a transport function.
Globulins:
• A diverse group including antibodies.
Fibrinogen:
• Soluble protein that polymerizes to form insoluble protein fibrin during clotting
Buffy Coat:
• These are leukocytes & platelets.
• Packed cells, mainly RBC.
Hematocrit:
• This is an estimate of the volume of packed RBC per unit volume of blood.
• Females 35-45% of volume of whole blood.
• Males 40-50%.
• Drop in hematocrit could mean anemia, not enough RBC being produced.
• Hematocrit of accident victims is closely monitored because sudden drop could indicate hemorrhage into the peritoneal cavity.
Differential Count:
• Neutrophils 55-60%
• Eosinophils 1-3%
• Basophils 0.7%
• Lymphocytes 25-33%
• Monocytes 3-7%
• Wright & Giemsa stains used for blood.
Erythrocytes:
• Main function is gas exchange.
• Fundamentally a biconcave reinforced bag of hemoglobin.
• 33% of RBC is hemoglobin.
• 66% water.
• Amount of hemoglobin: 13.5g/100 ml blood (female) and 15g/100ml blood (male).
• Total surface area 3,800 square meters.
• Normally never leave the circulation.
• No nucleus.
Abnormal Forms:
• Variation in size, shape & staining intensity diagnostic of various types of anemia (reduction below normal number of RBC).
Anisocytosis:
• Variation in size macrocytes - diameter greater than 9 micrometers microcytes - diameter less than 6 micrometers.
Poikilocytosis:
• Abnormal shape hyper- & hypochromia.
Why are RBCs Shaped Biconcavely?
• Biconcave shape increases surface area 30% more than a sphere.
• Shape also allows hemoglobin to be closer to the surface thereby decreasing the diffusion distance.
A and B Blood Groups:
• RBC plasmalemma contains inherited carbohydrates that act as antigens & are responsible for blood groups.
• The A & B antigens determine blood groups.
• Persons who lack the A or B antigen or both have antibodies against the missing antigen(s).
• If they are transfused with blood containing the missing antigen, that make antibodies against the RBC.
Rh Groups:
• Rh groups (first identified in Rhesus monkeys, hence the abbreviation) are a complex of more than 2 dozen antigens.
• Three of these Rh antigens (C, D & E) are common in the population such that 85% of Americans possess these antigens on their RBC surfaces and are thus said to be Rh+.
• When an Rh- pregnant woman delivers her first Rh+ baby, enough of the baby's blood is likely to enter her circulation to induce formation of anti-Rh antibodies.
• During a subsequent pregnancy with an Rh+ fetus, those antibodies will attack the RBC of the fetus causing erythroblastosis fetalis.
• Prenatal & postnatal transfusions are necessary to prevent death to the newborn unless the mother has received anti-Rh agglutins before or shortly after the birth of her first Rh+ baby.
Rouleaux:
• Columnar-shaped aggregate of RBC in stagnant blood on thick smears.
• Results from surface tension & glycoproteins on RBC surface.
Reticulocytes:
• They are immature RBC and are present as 1-2% of RBC.
• They are released from bone marrow and mature to RBC within 24-48 hours.
• They still contain rRNA in their cytoplasm and it stains with brilliant cresyl blue to appear as a thin filament.
• Used diagnostically: Elevated amounts indicates RBC are not being maintained 120 days but are being removed rapidly & bone marrow is trying to keep the RBC number up by releasing them before they are mature.
• In sickle cell, RBC are cleared in the spleen due to their spiny shape so marrow releases immature RBC to compensate.
• This shift to more immature cells is called a shift to the left.
• A rise in the proportion of circulating reticulocytes is called reticulocytosis.
Erythropoietin
• Reticulocyte number is controlled by the kidney hormone, erythropoietin.
• It stimulates the rate of production when the body is not getting enough oxygen.
• After RBC circulate 120 days, their plasmalemma becomes less flexible & protrusions form.
• They are cleared in the spleen & liver by macrophages.
• Iron present in hemoglobin is recycled back to the marrow & reused in hemoglobin production.
Megakaryocytes
• Megakaryocytes in bone marrow fragment along cell demarcation lines to break off cell fragments called platelets or thrombocytes.
• 150,000-400,000/mm2 blood.
• Stay in circulation 8-10 days before being cleared by the spleen.
• Platelets are involved in clotting and as such maintain the integrity of the cardiovascular system by repairing damaged endothelium by stimulating the fibrin system to produce clots.
Platelets
Platelets are 2-4 microns in diameter & have:
• Fuzzy coat - helps attach to a damaged site.
• Hyalomere - perimeter area adjacent to plasmalemma with marginal MT band & actin active in filopodia during migration & aggregation.
• Granulomere with granules alpha granules - contain factors that facilitate vessel repair, platelet aggregation & coagulation of blood.
• Ex. fibrinogen, platelet derived growth factor that stimulates proliferation of of smooth muscle & fibroblasts to help repair wound.
Granulomere
• Delta or dense granules contain factors that facilitate platelet aggregation & adhesion as well as vasoconstriction.
• Ex. calcium, serotonin which promotes smooth muscle contraction.
• Lambda granules - lysosomes that aid in clot resorption.
Events in clot formation
• Platelets have receptors for basement membrane components & collagen & adhere to an area of damaged endothelium.
• Binding causes degranulation of platelet contents.
• Serotonin causes lumen to narrow & blood flow is reduced.
• Clotting factors promote fibrin production & clot formation.
• Fibrin polymerizes into a meshwork, platelets change shape & become spiny & attach to fibrin.
• MT & MF in platelets interact to reduce the clot by 90%.
• Platelet derived growth factor stimulates fibroblast division & repair occurs.
• Clot is later dissolved.
Leukocytes
• White blood cells.
• Not permanent components of the blood.
• Migrate to tissues & perform various functions.
Granulocytes
• Contain specific granules with various functions & azurophilic granules (lysosomes).
• Granulocytes are named because of their staining characteristics.
Neutrophils
• Live 6-7 hours in circulation & 1-4 days in connective tissue.
• In acute infection they are the first troops into battle, they are the equivalent of calling 911.
• They leave the circulatory system at the site of infection & attack foreign agents by phagocytosis.
• Neutrophils can survive in anaerobic environment such as inflamed or necrotic areas.
In females the inactive X chromosome is condensed & present as a drumstick or Barr body. Nucleus has 2-5 segments.
Granules
1. Several different types specific for a variety of bacteria.
2. Involved in inflammatory response.
3. Ex. lactoferrin, phagocytin.
Azurophilic granules:
• Lysosomes.
Monocytes
• 2-8% of WBC.
• A lot of pale gray cytoplasm.
• Kidney shaped nucleus.
• Circulate only a few days, 8-10, then migrate to tissue where they differentiate into macrophages and assist neutrophils for several months.
• Monocyte-macrophage system consists of circulating, their bone marrow precursors & fixed macrophages.
• Kupffer cells of liver.
• Microglia Langerhans cells of skin.
• Antigen presenting cells of lymphoid organs.
Inflammation
Classic symptoms of acute inflammation:
• Swelling.
• Redness.
• Heat.
• Pain.
• Loss of function (Pyrexia = fever).
• Acute inflammation is a generally localized process that is initiated by an injurious agent, like bacteria.
• It can occur anywhere.
• To name it, attach -itis to the name of a body part, laryngitis, sinusitis, tonsillitis, appendicitis.
What happens in inflammation?
1. Transient vasoconstriction of arterioles, which may last only a few seconds, quickly followed by vasodilation via relaxation of arterioles & precapillary sphincters.
2. Endothelium of venules become leaky & plasma moves between cells margins out to the tissue spaces (exudation) causing edema that produces swelling & tissue tenderness due to pressure on sensory nerve endings.
3. Loss of function can be produced by build up of tissue fluid interfering with movements of the affected part.
4. Chemotaxis attracts neutrophils to the area of inflammation. (Emergency, call 911)
5. Neutrophils become "sticky" and attach to the walls of venules.
6. Neutrophils attach to the margins of the vessel walls, thus this attachment is called margination.
7. This process is mediated by P-selectins, etc.
8. Diapedesis occurs where neutrophils escape the circulation & enter the tissue space.
9. Neutrophils phagocytose the invading agent
10. Neutrophils are further stimulated by the presence of antigen-antibody complexes where an antigen has combined with an antigen of an invading agent.
11. Local accumulations of dead or dying neutrophils, broken down tissue cells & dead or dying pathogens form the creamy yellow pus.
12. Monocytes are attracted to the area & enter the tissue via diapedesis and assist neutrophils.
13. Monocytes are the "garbage men" they clean up after the initial battle. They hang around because they have a longer lifespan than neutrophils (months vs days).
14. If the inflammation continues, bone marrow greatly increases production of neutrophils & monocytes for months or even years, sometimes at the rate of production 20 to 50 times normal.
15. Fibroblasts enter the area to repair the connective tissue & new vessels sprout. The world of the "Tissue Wars" is once again peaceful & happy.
Basophils:
• 0.5-1% WBC
• Exact lifespan unknown but thought to be short.
• Are motile (mast cells are long lived & sessile)
• Nucleus is obscured by overlying granules.
• Mediate allergic responses.
• Granules with heparin & histamine.
• Can generate leukotrienes.
Eosinophils:
• 1-3% WBC Bilobed nucleus.
• Lifespan 6-10 hours in blood & 8-12 days in tissue.
• Limits duration & intensity of allergic response.
• Neutralizes histamine.
• Inhibits vasoactive substances produced by mast cells & basophils.
• Inhibits mast cell degranulation.
• Controls infections by parasitic larvae.
• Have affinity for antigen-antibody complexes.
Lymphocytes:
• 20-50% WBC.
• Large nuclear to cytoplasmic ratio.
• Thin rim of blue cytoplasm.
• Many functionally different types.
• B lymphocytes differentiate in bone marrow & mediate humoral immunity, a process that requires the presence of immunoglobulins in the blood.
• T lymphocytes differentiate in the thymus & mediates cellular immunity, a process that requires living cells as opposed to immunoglobulins.
B lymphocytes:
• When stimulated by antigen proliferate & differentiate into plasma cells that produce antibodies.
• Found in mammary glands, epithelia, spleen, lymph nodes.
T lymphocytes:
• T lymphocytes occur as several types, most lymphocytes in the blood (80%) are T lymphocytes.
• Helper T cells - regulate activity of T & B cells positively.
• Suppressor T cells - regulate T & B negatively.
• Cytotoxic T cells (killer T cells, natural killer cells) kills other cells including tumor cells, virus-infected cells & foreign grafts.
• Null cells - may represent circulating stem cells.
Immunologic Memory:
• Both T & B cells have immunologic memory.
• Once exposed to an antigen, lymphocytes undergo mitosis and some form Effector cells, ex. B cells differentiate into plasma cells & produce antibodies.
• Memory cells remain quiescent until they encounter the antigen again & can mount a rapid & vigorous response.
Prenatal Hematopoiesis
• Mesoblastic phase - occurs in blood islands of the embryo yolk sac from week 2-6 (mesoblast = mesoderm).
• Generally produce nucleated RBC.
• Hepatic phase -at 6 weeks blood islands form in the liver primordium & produce non-nucleated RBC.
• In month 2 granulocytes & megakaryocytes appear & somewhat later in the spleen.
• Myeloid phase - occurs in month 4 when blood vessels invade the cartilage model & stem cells enter the circulation & are carried to marrow where they take up residence.
How does multi-organ hematopoiesis occur?
• It is believed that the successive sites of hemopoiesis are seeded by stem cells carried in the bloodstream from the previous site of blood formation.
• All blood cells arise from a single stem cell in marrow.
• It is pluripotential because it can produce all blood cell types.
• These proliferate to form.
Lymphoid and myeloid cells
1. Lymphoid cells that become lymphocytes that differentiate in lymph nodes, spleen & thymus.
2. Myeloid cells that develop in marrow. Both of these cell lines are multipotential stem cells because their potential is restricted only to certain types of cells.
Bone Marrow:
• Red bone marrow hemopoietically active; 10% of adult marrow.
• In adults in pelvis, ribs, sternum, body of vertebrae, bones of cranial vault, cancellous regions of femur & humerus.
• Yellow bone marrow is mostly fat.
• In newborns, all marrow is red but most later becomes yellow.
Erythropoiesis:
• Takes about 1 week.
General tendencies:
• Smaller cell round nucleus cytoplasm from very basophilic to acidophilic loss of nucleus & organelles.
Polychromatophilic Erythroblast:
• Last stage capable of division.
• Mixed red/blue cytoplasm.
• Nucleus checkered.
• No nucleolus, ribosome production stops.
• More hemoglobin, more eosinophilia.
• Basophilic erythroblast.
• Hemoglobin synthesis begins.
• Proerythroblast (erythroblast, rubriblast).
• Royal to pale blue cytoplasm due to many ribosomes.
Orthochromatophilic Erythroblast:
• Acidophilic erythroblast.
• Eccentric condensed dark nucleus extruded & cleared by macrophages in marrow.
Reticulocyte
Few remaining ribosomes stained with brilliant cresyl blue.
• No nucleus.
• In a few days become mature RBC.
• A reserve of reticulocytes is greater than in the circulation.
RBCs cleared
• Old RBCs are cleared in the spleen & iron liberated from degradation of hemoglobin is returned to marrow for reuse.
• Bone marrow can produce 6 million RBC/sec.
Granulopoiesis
General tendencies:
• Condensation & lobulation of nucleus.
• Development of granules.
Myelocyte
• Round nucleus.
• Smaller.
• Greater number of specific granules.
• Last cell capable of mitosis.
Promyelocyte
• Basophilic cytoplasm & azurophiloc granules (lysosomes).
Myeloblast
• Large irregular nucleus & moderately basophilic cytoplasm.
Metamyelocyte
• Nucleus denser & indented.
• Specific granules 80% of granule population Band or stab cell Nucleus horse-shoe shaped & lobes form mature cell.
Lymphopoieis & Monopoiesis
Although these processes occur in marrow, immature stages are not readily identifiable.
T lymphocyte formation
• Stem cell in marrow travels to thymus.
• All immature T cells produced by age 10 when the thymus degenerates.
• Travel to spleen.
• When T cells encounter an antigen they respond by making thousands of T cells specific for that antigen.
• Have a very long life span.
B lymphocyte formation
Stem cells in marrow Travel to spleen where similar steps as previously stated occur.
Additional Reading:
Basic Histology
1. Introduction to Histology
2. Basic Cell Physiology
3. Actin, Microtubules, and Intermediate Filaments
4. Mitochondria, Nucleus, Endoplasmic Reticulum, Golgi
5. Epithelium (Epithelial Tissue)
6. Connective and Adipose Tissue
7. Types of Cartilage
8. Osteogenesis
9. Nervous Tissue
10. Muscle Tissue
11. Cardiovascular System
12. Blood and Hematopoiesis
13. Lymphoid Tissue
14. Digestive Tract I: Oral Cavity
15. Digestive Tract II: Esophagus through Intestines
16. Liver, Pancreas, and Gall Bladder
17. Respiratory System
18. Integument
19. Urinary System
20. Endocrine System
21. Male Reproductive System
22. Female Reproductive System
23. Eye and Ear
Medical Images
Useful Medical Images & Diagrams (link opens in a new window)
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