4 elements of blood
RBC, WBC, platelets, plasma
Volume of blood which is composed of cells relative to the total volume
Hematocrit
When hematocrit is low
<30% Anemia
When hematocrit is high
> 60% Polycythemia
Most common plasma protein
Albumin
Types of globulins
Gamma (immuno), alpha and beta (non-immune)
Inactive form of thrombin
Prothrombin
Plasma protein that in a cascade of blood clotting reactions is transformed into fibrin
Fibrinogen
Formed elements of human blood
Blood cells and platelets
Fills erythrocytes
Hemoglobin
Peripheral membrane protein that forms a meshwork of fibers on the cytoplasmic side of the plasma membrane
Spectrin
Provides binding between spectrin filaments and integral membrane proteins
Ankyrin
Mutation of spectrin
Hereditary spherocytosis
Characterized by the presence of red blood cells of different size in the peripheral blood
Anisocytosis
When RBCs are irregularly shaped
Poikilocytosis
Parts of hemoglobin HbA
2 alpha and 2 beta
Hemoglobin HbA2
2 alpha and 2 delta
Hemoglobin HbF
2 alpha and 2 gamma
What vitamin is necessary for incoporation of iron into the RBC?
B12
Cause of sickle cell anemia
Point mutation in beta globin chain of hemoglobin A
Universal blood recipients
AB
When Rh+ of newborn reacts with Rh- mom resulting in IgG crossing the placenta
Erthroblastosis fetalis
What do you give Rh (-) moms with Rh (+) babies?
RhoGAM
Condition with more than 12,000 WBC per mm3
per mm3 is called what?
Leukocytosis
Condition with less than 5,000 WBC is called what?
Leukopenia
2 Major categories of WBCs
Granulocytes and agranulocytes
3 types of granulocytes
Neutrophils, eosinophils, basophils
Classic characteristic of granulocytes
nuclues divided into lobes, hence why they are names polymorphonuclear leukocytes (PMNs)
2 major types of granules in granulocytes
Azurophilic and specific granules
Staining of asurophilic granules
purple
Staining of specific granules
dark blue (basophilic
granules), orange (eosinophilic granules), or do not stain at all (neutrophilic
granules)
Which WBCs can divide and which cannot?
Granulocytes are non-dividing, agranulocytes can divide
2 Types of agranulocytes
Lymphocytes and monocytes
Most common WBC in the peripheral blood
Neutrophil
Appearance of neutrophils
Fairly large cells with mulilobed nuclei (have Barr body in females that looks like a drumstick)
3 types of granules in neutrophils
Neutrophilic bactericidal proteins, asurophilic (lysosomes), tertiary (gelatinase and glycoproteins)
What diseases is neutropenia associated with?
autoimmune dieases and acquired immune deficiency syndrome
What is formed when endothelial cell cyotkines trigger neutrophils to adhere to the walls?
Marginating pool
After adhering to the endothelial wall, what happens to neutrophils?
Migrate into the tissue thru the endothelium of the postcapillary venules to become tissue neutrophils
What type of immunity are neutrophils associated with?
Cell-mediated immunity via phagocytosis of bacteria
What does the binding of chemotatic agents to the plasma membrane of a neutrophil cause?
The release of tertiary and neutrophilic granules
What interleukin do neutrophils produce and what does it do?
IL-1 induces fever
Morphology of eosinophils
Bilobed nucleus with numerous granules
Types of eosinophilic granules
Cytotoxins, neurotoxins, histaminase
Role of cytotoxins
Designed to destroy protozoan and helminthic parasites. (Includes major basic protein, eosinophil cationic protein, and eosinophil peroxidase)
Role of neurotoxin
Designed to cause dysfunction in the parasite’s nervous system
When are eosinophils commonly found in the peripheral blood?
Parasitic infections and allergic reactions
Rarest WBC
Basophil
Morphology of basophils
Smallest granulocyte, lobed nucleus, basophilic granules with histamine and heparin
Major function of basophils
Produce histamines
When are basophils most commonly found in the peripheral blood?
Chronic granulocytic leukemia and chicken pox
Most common agranulocyte
Lymphocytes
3 main types of lymphocytes?
T cells, B cells, Natural Killer Cells
Most common type of lymphocyte
T cell
Where do T cells mature?
Thymus
How are T cells characterized?
T cell receptor and CD3
What do T cells produce?
Cytokines to direct and recruit other cells of the immune system
3 Types of T cells
T helpers, Regulatory T cells, Cytotoxic T Cells
Characteristics of T helper cells
CD4+, cytokines activate/stimulated B cell proliferation/differentiation, promotes cell mediated immunity, activates macrophages/T cells/mast cells
Characteristics of Regulatory T cells
CD4+, cytokines inhibit functions of other leukocytes, inhibit autoimmunity
Characteristics of Cytotoxic T cells
CD8+, activated by helper Ts, destroy cells carrying antigen (cell mediated immunity)
Cell responsible for transplant rejections
Cytotoxic T cells
Main function of B cells
Produce antobodies (Ig) aka humoral immunity
Characteristics of B cells
surface immunoglobin
Activation of B cells
1 exposure triggers primary immune response, small B cells go thru maturation and get programmed into large lymphocytes, divide into plasma cells to produce antibodies
Large lymphocytes programmed during their development to kill certain virus-infected calls and some types of tumor cells
Natural Killer cells
Blood cancer that involves undifferentiated precursor cells
Acute lymphocytic leukemia
Blood cancer that involves partially differetiated cells
Chronic lymphocytic leukemia
Characteristics of monocytes
Large cells, kidney-shaped nucleus, cytoplams with many lysosomes and mitochondria
Anucleate particles that are abundant in human blood
Platelets
2 main parts of platelets
Peripheral zone (hyalomere) and Central zone (granulomere)
Components of hyalomere of platelets
Cytoskeletal elements
Components of granulomere of platelets
Lysosomes, alpha granules, dense granules
Contents of alpha granules
Adhesion proteins, clotting factors (vWF and fibrogen)
Contents of dense granules
Factors involved in platelet adhesion (serotonin and ADP)
What happens when collagen in exposed in a damaged blood vessel?
Platelets adhere to collagen
Released by platelets to promote adhesion and vasoconstriction
Thromboxane, serotonin, ADP
Causes the clot to contract
Actin and myosin filaments of the platelet cytoskeleton
Released by adhered platelets’ alpha granules
Platelet thromboplastic factor (coagulation factor)
What is platelet thromboplastic factor’s role?
Converts inactive prothrombin into thrombin
Role of fibrin
Forms a dense meshwork of fibers in the area where the blood vessel is damaged that acts as the skeleton for the clot
Provides a sticky surface for clot assembly
Platelets
Autoimmune disease that is caused by the deficiency pf platelets
Thrombocytopenia
Signs and symptoms of thrombocytopenia
Larger and more active platelets formed, spontaneous hemorrhages (beneath skin and mucous membranes), Tx with steriods
Process of blood cell formation
Hemopoiesis
Origin of blood cells
Mesodermal and arise from mesenchyme
Precursor blood cell
Hemopoietic stem cell (aka pluripotential blood stem cell PPSC)
2 Major progenitor cells from HSC
Common myeloid progenitor and common lymphoid progenitor
What do common myeloid progenitors give rise to?
Megakeryocyte/Erythocyte progenitors (forms RBCs, magekaryocytes, and platelets) and Granulocyte/monocyte progenitors ((neutrophils, eosinophils, and basophils), mast
cells, and monocytes.
What do common lymphoid progenitors give rise to?
T/B cells and NKC
What stimulates hemopoiesis?
Colony-stimulating factors
produced by macrophages, endothelial cells, and fibroblasts. It
stimulates the formation of granulocytes
Granulocyte CSF aka filgrastim
produced by T-lymphocytes, endothelial cells, and fibroblasts. It stimulates the production of granulocytes and macrophages
Granulocyte + macrophage CSF aka sargramostim
produced by macrophages, endothelial cells, and fibroblasts.
It stimulates the formation of macrophages
Macrophage CSF
Produced by T cells to stimulate the production of all myeloid cells
Interleukin-3
Produced in the kidney cells to stimulate RBC production
Eryhtropoietin aka epoetin
Stimulates production and differentiation of megakaryocytes and increases platelet count.
Thrombopoietin (clinically used to improve clotting)
Produced by the stromal cells in the bone marrow and stimulates the production of platelets similar to TPO
IL-11 aka oprelvekin
4 major phases of prenatal hemopoeisis
Mesoblastic, hepatic, splenic, myeloid
Phase that begins during the 2nd week of development. When blood islands are formed from the yolk sack mesenchyme
Mesoblastic phase
Phase that begins during the 6th week of development. Nucleated erythrocytes are present during this stage and white blood cells start appearing by the 8th week
Hepatic phase
Phase that begins during the 12th week of development and continues along with the hepatic stage
Splenic phase
Phase that takes place in bone marrow, begins durign the 5th month and continues into postnatal stage
Myeloid phase
6 Stages of erythropoiesis
Proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, Orthochromatophilic erythroblast, Reticulocyte, mature erythrocyte
Erythroblast phase with a deeply basophilic sytoplasm and hemoglobin form a distinctive lake
Basophilic erthroblast
Erythroblast phase that exhibits mitotic activity
Polychromatophilic erythroblast
Erythroblast phase with a smal, dense nucleus with a pinkish hempglobin
Orthochromatophilic erythroblast postmitotic cell
What does the presense of reticulocytes in the peripheral blood indicate?
Increased levels of RBC production in the bone marrow
5 stages of Granulopoiesis
Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band form, mature neutrophil
Largest cell in the granulopoiesis lineage
Promyelocyte (contains azurophilic granules)
Stage of granulopoiesis that contains specific granules and exhibits activity
Myelocyte
Stage of granulopoiesis that does not exhibit mitotitic activity
Metamyelocyte
Stage of granulopoiesis that has a horse-shaped nucleus
Band form
Stages of monocytopoiesis
Monoblast, promonocyte, monocyte
Stages of thrombopoiesis
Megakaryoblast, megakaryocyte
Formed from the megakaryocyte
Platelet