Histology 2: Blood and Hemopoiesis Flashcards
Relative % of total blood volume that is HCT? What is considered clinically anemia? What is considered clinically polycythemia?
Normal HCT is approx. 45% of total blood volume with plasma making up the remaining ~55%.
Anemia is an HCT below 30%
Polycythemia is HCT above 60%
Importance of Albumin?
Accounts for 1/2 of plasma protein and is made in the liver.
Most important for regulation of colloid osmotic pressure of blood, helps maintain blood/tissue fluid volumes.
Acts as carrier protein and aids in transport of hormones, metabolites and drugs.
Two important clotting factors, and function in clotting cascade.
Prothrombin: inactive form of thrombin. Thrombin in an enzyme that facilities platelet aggrigation and in the presence of Ca++ converts fibrinogen to fibrin.
Fibrinogen: largest plasma protein, converted to fibrin. Fibrin polymerizes and forms a dense network at sides of blood vessel damage (i.e. clot).
Erythrocytes: function, characteristics, 2 important plasma membrane components.
Carries gases in blood vessels.
Biconcave disk, 7.5 um diameter, 2.6 um thick at edge and 0.75 um thick at center.
Mature RBC’s do not have organelles.
Spectrin: forms network on cytoplasmic side of plasma membrane. Bind find to actin and to Ankyrin.
Ankyrin: provides binding between spectrin filaments and integral membrane proteins (band 3 protein)
Clinically important info about erythrocytes, mutations of membrane proteins, pathological morphological changes in erythrocytes.
Hereditary Spherocytosis: result of mutation in spectrin gene in that the erythrocyte is unable to maintain biconcave shape and becomes spherical.
Anisocytosis: presence of red blood cells of varying size in peripheral blood.
- -Megalocytes: abnormally large RBCs >9um
- -Poikilocytosis: irregularly shaped RBCs, w/ diameter < 6um called microcytes.
Which live longer, mononuclear agranulocytes or polymorphonuclear granulocytes?
Mononuclear agranulocytes
What types of leukocytes are polymorphonuclear granulocytes?
Neutrophils
Eosinophils
Basophils
What types of leukocytes are mononuclear agranulocytes?
Lymphocytes
Monocytes
Neutrophils: relative abundance, cellular morphology, life cycle, functions.
Comprise 60-70% of blood leukocytes, 3,000-6,000/uL blood.
Fairly large cells, multilobed nuclei, few mitochondria, often called polymorphonuclear leukocytes (PMNs).
Females have a second x-chromosome which shows up as a Barr-body on the nucleus and is drumstick shaped.
3 types of granules present:
- Azurophilic: non-specific/primary, represent lysosomes
- Neutrophilic: specific/secondary, lysozymes and lactoferrins
- Tertiary: gelatinase and collagenases
Produced in bone marrow and released into circulation. Life span of 1-4 days in tissue.
First line of defense, endocytosis of particles and then destroyed with Respiratory Burst.
Produce IL-1, which induced fever
Eosinophils: relative abundance, cellular morphology, life cycle, functions.
Rare in peripheral blood (2-4%)
Similar size to neutrophils, bilobed nucleus.
Contain eosinophilic (specific) granules and azurophilic granules.
- Cytotoxins: designed to destroy protozoan and helminthic parasites. Major Basic Protein (MBP), eosinophil cationic protein (ECP) and eosinophil peroxidase.
- Neurotoxins: eosinophil-derived neurotoxin, causes neuro dysfunction in parasites.
- Histaminase: breaks down histamine
Most common during parasitic infection (ex. trichinosis).
Phagocytize antigen-antibody complexes and modulate inflammatory response.
Also increase numbers during allergic reactions and help break down histamine and inhibit mast cell degranulation.
Basophils: relative abundance, cellular morphology, life cycle, functions.
Rares of WBCs in normal blood smears (0.5-1.5%)
Smallest granulocyte (8-10um), bilobed nucleus, contain basophilic granules which contain histamine and heparin.
Major function is the production of histamine, very similar to Mast Cells. Commonly seen during chronic granulocytic leukemia and chicken pox.
Lymphocytes: relative abundance, cellular morphology, life cycle, functions.
Second most common WBC (20-30%), most common agranulocyte.
Vary in size from 6-14um, depending on stage of development.
3 subtypes:
T-lymphocytes
B-lymphocytes
Natural Killer (KN) cells
T-lymphocytes: types, characteristics
Arise from bone marrow but mature in thymus. Characterized by T-cell receptor on surface. Produce cytokines to help recruit and direct other immune cells.
T-Helper cells:
-acive and stimulate proliferation of B-cells, stimulate proliferation of B-cells into plasma cells. Activate and proliferate T-cells, activate Mast Cells, activate Macrophages and increase phagocytosis.
T-Cytotoxic Cells (CD4):
-activated by TH cells and destroy antigen presenting cells. Responsible for destroying infected cells and also responsible for the transplant rejection.
Supressor T lymphocytes (CD8):
-suppress antibody formation by B cells, down regulate ability of T cells to initiate a cellular response.
B lymphocytes: characteristics
Arise and mature in bone marrow.
Function is to produce antibodies (immunoglobin). Reside in lymphoid and connective tissues.
Natural Killer (NK) Cells
large lymphocytes that are programmed during development to kill certain virus-containing cells and some types of tumor cells.
Acute vs. Chronic Lymphocytic Leukemia
Acute: rapidly progressing blood CA involving undifferntiated precursor cells. More common in children, responds well to treatment.
Chronic: slow progression, involves partially differentiated cells. Responds poorly to treatment but in many cases is indolent.
Monocytes: characteristics, types/examples, function.
Circulate in peripheral blood and adhere to vessel walls, moving by ameboid movement.
Differentiate in body tissues into the various parts of the mononuclear phagocytic system including; macrophages, osteoclasts, alveolar macrophages, liver Kupffer cells, macrophages of lymph nodes, speen and microglial cells of brain.
Make up 4-6% of peripheral blood leukocytes.
Can be very large (12-20 um)
Bean shaped nucleus
Basophilic cytoplasm w/ many small azurophilic granules (lysozymes), well developed Golgi, small amount of RER and many small mitochondria.
Platelets; structure, zones, characteristics
Anucleated particles abundant in blood (200,000-400,000/mL)
Lifespan of 8-10 days
Biconvex discoid cell particles, diameter between 2-4um
Few mitochondria and many granules
Peripheral zone/hyalomere, made mostly of cytoskeletal elements including G-actin, F-actin and spiral of microtubles which help form the discoid shape.
Central zone/granulomere, contains 3 types of vesicles; lysozomes, a-granules, dense granules.
- -alpha-granules contain clotting factors such as von Willebrand factor, thromboplastic factor, fibrinogen.
- -Dense granules contain factors involved in platelet adhesion such as serotonin, ADP. Serotonin is also a vasoconstrictor.
Common myeloid progenitor cell lineage derivatives (CFU-GEMM):
Megakaryocyte/Erythrocyte Progenitor (M/EP) cells - platelets and erythrocytes
Granulocyte/monocyte Progenitor (G/MPs or CFU-GM) cells: differentiate into the precursors for neutrophils, eosinophils, basophils, and monocytes.
Common lymphoid progenitor cell lineage derivatives (CFU-L)
Give rise to T lymphocytes, B lymphocytes, and NK cells
Major Colony-Stimulating Factors (CSF):
Granulocyte-CSF: produced by macrophages, endothelial cells, fibroblasts.
Macrophage-CSF: produced by macrophages, endothelial cells, fibroblasts.
Granulocyte + Macrophage-CSF: produced by T-lymphocytes, endothelial cells, fibroblasts.
Interleukin 3 (IL-3): produced by T lymphocytes. Stimulates production of all myeloid cells.
Erythropoietin (EPO): produced by kidney cells. Stimulates RBC production.
Prenatal to Postnatal Hemopoieses; locations and timing
Prenatal:
- Mesoblastic phase: 2nd week of embryonic development, blood islands formed in yolk sack mesoderm. Erythroblasts present at this stage.
- Hepatic phase: 6th week of development, continues to 5-7th months. Nucleated erythrocytes present, WBCs begin appearing at 8th week.
- Splenic phase: starts in 12th week, continues w/ hepatic phase until 5-6th months.
- Myeloid phase: bone marrow, beings in 5th month.
Postnatal:
- only in bone marrow.
- immature cells are largest; prominent euchromatic nucleus, predominate nucleoli, dark-staining basophilic cytoplasm secondary to intense protein synthesis.
Erythropoiesis (erythroid CFU-E lineage): 5-6 stages.
Starts from common myeloid progenitor cells (CMP). Stimulated by hypoxia, high altitude, anemia, hemorrhage.
Stimulated by:
-erythropoietin (EPO), IL-3
Proerythroblast:
-largest cell, actively dividing, large spherical nucleus, 1-2 nucleoli, deeply basophilic cytoplasm, organelles and ribosomes abundant, HgB present.
Basophillic erythroblast:
-reduced size, chromatin is more dense (heterochromatic), nucleus 70% original size, DEEPLY BASOPHILIC cytoplasm, organelles still present.
Polychromatophilic erythroblast:
-stains acidophilia and basophilia due to increasing HgB, distinctive checkerboard pattern to cytoplasm staining. Still has mitotic activity.
Normoblast or orthochromatophilic:
-small in size, dense nucleus 25% original size, cytoplasm is pinkish (eosinophilic) from HgB.
Reticulocyte:
-nucleus is extruded and ingested by macrophage. No longer mitotically active. 80% of mature HgB levels, 4 days to develop into RBC. Normally account for 1-2% total erythrocytic count, if elevated shows active RBC production in bone marrow.
Granulopoiesis (granulocyte-monocyte CFU lineage CFU-GM); influencing factors, stages
Stimulated by:
-G-CSF, GM-CSF, IL-3.
Myeloblast:
-large cell, oval euchromatic nucleus, 3-5 nucleoli, basophilic cytoplasm w/o granules, ribosomes and RER present, mitotically active.
Promyelocyte:
-largest cell in lineage, clumping of chromatin. Cytoplasm basophilic w/ azurophilic granules (lysosomes) present (produced only at this stage). Mitotically active.
Myelocyte:
-still large cell, smaller nucleus. First stage to exhibit SPECIFIC GRANULES (baso, eosino, neutro). Golgi complex forms clearing around nucleus called perinuclear clear zone. Mitotically active.
Metamyelocyte:
-bean shaped heterochromatic nucleus, SPECIFIC GRANULES well expressed, NO MITOTIC activity.
Band Form:
-stage just before lobulation, horseshoe shaped nucleus, 1-2% of blood granulocytes normally, if increased called a “left shift”, possibly indicative of granulocytic leukemia.
Segmented stage:
-last stage, nucleus is segmented and loved; multilobed (neutrophil), bilobed (eosinophil and basophil).
Monocytopoiesis (granulocyte-monocyte CFU lineage CFU-GM); influencing factors, stages
Influenced by:
M-CSF, GM-CSF, IL-3.
GMP stem cells also give rise to dendritic cells.
Monoblast: large cell that resembles myeloblast
Promonocyte: small cells w/ basophilic cytoplasm, clearly indented nucleus, nucleoli present.
Monocyte: large amount of RER, fine azurophilic granules. Mature monocytes enter blood stream and mature in tissue as macrophages.
Lymphopoiesis; progenitor cell, location, derivatives
Common lymphoid progenitor cell (CLP), becomes T cells, B cells, and NK cells.
Formation takes place in bone marrow but programming takes place in thymus (T cells), bone marrow/GALT (B cells), lymph nodes (NK cells).
Thrombocytopoiesis (Megakaryocyte CFU lineage); lineage, influencing factors.
Produced in bone marrow from common myeloid progenitor (CMP) cells.
Influenced by IL-3, GM-CSF.
Megakaryoblast: large stem cell formed from stem cell w/o cytokinesis, results in polyploid cells, nucleus is ovoid and slightly indented.
Megakaryocyte: gigantic polyploid cell, 16n. Very large, lobulated nucleus. As cytoplasm is pinched off platelets are formed (4000-8000 per)
Blood clotting cascade; steps, factors.
- Collagen exposed by damage to blood vessel, platelets adhere to collagen.
- Platelets activated and release THROMBOXANE, SEROTONIN, ADP.
- Actin and Myosin slide along one another, bringing the exposed edges of vessel into approximation. Clot contracts.
- Platelets adhere to one another and release Alpha-granules which contain platelet thromboplastic factor.
- Platelet thromboplastic factor converts prothrombin to thrombin.
- Thrombin converts fibrinogen to fibrin.
- Fibrin forms dense meshwork and act as skeleton for clot
- Platelets provide sticky surface for clot assembly.
