Carlos Shared "22 Hematology" - 146 Picmonics

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22 Hematology

Erythrocyte (RBCs)
Carries O2 to tissues and CO2 to lungs.
Anucleate and lacks organelles; biconcave (image) , with large surface area-to-volume ratio for rapid gas exchange.
Life span of 120 days.
Source of energy is glucose (90% used in glycolysis, 10% used in HMP shunt).
Membrane contains Cl−/HCO3 − antiporter, which allows RBCs to export HCO3 − and transport CO2 from the periphery to the lungs for elimination.
Spectrin is the cytoskeletal protein that gives the erythrocyte its shape
Types
Erythrocytosis = polycythemia = increased hematocrit.
Anisocytosis = varying sizes
Poikilocytosis = varying shapes
Reticulocyte = immature RBC; reflects erythroid proliferation.
Bluish color on Wright-Giemsa stain (a supravital stain) of reticulocytes represents residual ribosomal RNA.
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Thrombocyte (platelet)
Involved in 1° hemostasis
Small cytoplasmic fragment derived from megakaryocytes
Life span of 8–10 days
When activated by endothelial injury, aggregates with other platelets and interacts with fibrinogen to form platelet plug
Contains dense granules (ADP, Ca2+) and α granules (vWF, fibrinogen, fibronectin).
Approximately 1⁄3 of platelet pool is stored in the spleen.
Thrombocytopenia or decreased platelet function results in petechiae.
vWF receptor: GpIb
Fibrinogen receptor: GpIIb/IIIa
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WBC Differential Lab Value
White Blood Cells (WBC)
5-10 (5,000-10,000)
Leukocyte Differential
Neutrophils (50%-70%)
Bands (2%-5%)
Segs (50%-70%)
Lymphocytes (20%-40%)
Monocytes (4%-8%)
Eosinophils (2%-4%)
Basophils (0.5%-1.5%)
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Neutrophil
Acute inflammatory response cell.
Increased in bacterial infections.
Phagocytic.
Multilobed nucleus (Image)
Specific granules contain leukocyte alkaline phosphatase (ALP), collagenase, lysozyme, and lactoferrin.
Azurophilic granules (lysosomes) contain proteinases, acid phosphatase, myeloperoxidase, and β-glucuronidase.
Hypersegmented neutrophils (nucleus has 6+ lobes) are seen in vitamin B12/ folate deficiency.
Increased band cells (immature neutrophils) reflect states of increased myeloid proliferation (bacterial infections, CML).
Important neutrophil chemotactic agents: C5a, IL-8, LTB4 (Leukotriene B4), kallikrein, platelet-activating factor.
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Monocyte
Differentiates into macrophage in tissues
Large, kidney-shaped nucleus (Image)
Extensive “frosted glass” cytoplasm.
Found in blood
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Macrophage
Phagocytoses bacteria, cellular debris, and senescent RBCs.
Long life in tissues.
Macrophages differentiate from circulating blood monocytes (Image)
Activated by γ-interferon
Can function as antigen-presenting cell via MHC II
Name differs in each tissue type (eg, Kupffer cells in the liver, histiocytes in connective tissue)
Important component of granuloma formation (eg, TB, sarcoidosis)
Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock
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Eosinophil
Defends against helminthic infections (major basic protein)
Bilobate nucleus
Packed with large eosinophilic granules of uniform size (Image)
Highly phagocytic for antigenantibody complexes
Produces histaminase, major basic protein (MBP, a helminthotoxin), eosinophil peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin.
Causes of eosinophilia = NAACP
Neoplasia
Asthma
Allergic processes
Chronic adrenal insufficiency
Parasites (invasive)
Immune response to helminths
Eosinophils act by type I and type II hypersensitivity reactions in responding to helminths
Type I— neutralization of histamine and leukotrienes
Type II—eosinophils attach to surface of helminths via IgE and release cytotoxins (eg, major basic protein) contained in their granules
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Basophil
Mediates allergic reaction
Densely basophilic granules (image) contain heparin (anticoagulant) and histamine (vasodilator)
Leukotrienes synthesized and released on demand
Basophilic—staining readily with basic stains
Basophilia is uncommon, but can be a sign of myeloproliferative disease, particularly CML
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Mast cell
Mediates allergic reaction in local tissues.
Mast cells contain basophilic granules (image) and originate from the same precursor as basophils but are not the same cell type.
Can bind the Fc portion of IgE to membrane.
IgE crosslinks upon antigen binding causes degranulation, leading to release of histamine, heparin, tryptase, and eosinophil chemotactic factors.
Involved in type I hypersensitivity reactions
Cromolyn sodium prevents mast cell degranulation (used for asthma prophylaxis).
MAST CELLS ACTIVATED BY
Tissue trauma
Complement proteins C3a and C5a
Cross-linking of cell-surface IgE by antigen
antigen response
Immediate response involves release of preformed histamine granules, which mediate vasodilation of arterioles and increased vascular permeability.
Delayed response involves production of arachidonic acid metabolites, particularly leukotrienes.
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Dendritic cell
Highly phagocytic antigen-presenting cell (APC) (Image)
Functions as link between innate and adaptive immune systems
Expresses MHC class II and Fc receptors on surface
Called Langerhans cell in the skin.
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Lymphocyte
Refers to B cells, T cells, and NK cells
B cells and T cells mediate adaptive immunity
NK cells are part of the innate immune response
Round, densely staining nucleus with small amount of pale cytoplasm (image)
Lymphocytes are highly sensitive to radiation; lymphopenia is the earliest change to emerge after whole body radiation
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B cell
Part of humoral immune response.
Originates from stem cells in bone marrow and matures in marrow.
Migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue).
Undergo immunoglobulin rearrangements to become naive B cells that express surface IgM and IgD.
When an antigen binds to surface IgM or IgD, B cells differentiate into plasma cells (which produce antibodies IgM or IgD) and memory cells.
Can function as an APC to CD4+ helper T cells via MHC II
CD40 receptor on B cell binds CD40L on helper T cell, providing 2nd activation signal.
Helper T cell then secretes IL-4 and IL-5 (mediate B-cell isotype switching, hypermutation, and maturation to plasma cells).
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T cell
Mediates cellular immune response.
Originates from stem cells in the bone marrow, but matures in the thymus.
T cells use TCR complex (TCR and CD3) for antigen surveillance
T cells differentiate into cytotoxic T cells (express CD8, recognize MHC I), helper T cells (express CD4, recognize MHC II), and regulatory T cells.
CD28 (costimulatory signal) necessary for T-cell activation. B7 on APC binds CD28 on CD4+ helper T cells providing 2nd activation signal
Activated CD4+ helper T cells secrete cytokines that "help" inflammation and are divided into two subsets.
Th1 subset secretes IL-2 (T cell growth factor and CD8+ T cell activator), IFN-y (macrophage activator) and IL-12 (Induces differentiation of T cells into Th1 cells.)
Th2 subset secretes IL-4 (facilitates B-cell class switching to IgG and IgE), IL-5 (eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA), and IL-10 (inhibits Th1 phenotype).
The majority of circulating lymphocytes are T cells (80%).
CD4+ helper T cells are the primary target of HIV.
Helper T cell secretes TGF-β, IL-6 and differentiates into Th17
TGF-β helps differentiate helper T cells into Treg (T cell regulator cells)
IL-4, IL-10 inhibit Th1 differentiation
IFN-γ inhibits differentiation into Th2
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Plasma cell
Produces large amounts of antibody specific to a particular antigen
“Clock-face” chromatin distribution and eccentric nucleus
Abundant RER
Well-developed Golgi apparatus
Found in bone marrow and normally do not circulate in peripheral blood
Multiple myeloma is a plasma cell cancer
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Fetal Erythropoiesis
YOLK SAC
3–8 weeks
Liver
6 weeks–birth
Spleen
10–28 weeks
Bone marrow
18 weeks to adult
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Hemoglobin development
Embryonic globins: ζ and ε.
Fetal hemoglobin (HbF) = α2γ2
Adult hemoglobin (HbA1) = α2β2
HbF has higher affinity for O2 due to less avid binding of 2,3-BPG, allowing HbF to extract O2 from maternal hemoglobin (HbA1 and HbA2) across the placenta.
HbA2 (α2δ2) is a form of adult hemoglobin present in small amounts.
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Blood Types and Compatibilities
ABO Compatibility
No Antigens (Type O Blood)
Universal Donor
A Antigen (Type A Blood)
B Antigen (Type B Blood)
AB Antigen (Type AB Blood)
Universal Recipient
Rhesus (Rh) Compatibility
Rh (Rhesus) Antigen
Never Rh+ to Rh-
Considerations
Blood Transfusion
Obstetric Patient
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Rh hemolytic disease of the newborn
IgM does not cross placenta; IgG does cross placenta.
Rh⊝ mothers exposed to fetal Rh⊕ blood (often during delivery) may make anti-D IgG.
In subsequent pregnancies, anti-D IgG crosses the placenta leading to hemolytic disease of the newborn (erythroblastosis fetalis) in the next fetus that is Rh⊕.
Administration of anti-D IgG (RhoGAM) to Rh⊝ pregnant women during third trimester and early postpartum period prevents maternal anti-D IgG production.
Rh⊝ mothers have anti-D IgG only if previously exposed to Rh⊕ blood.
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ABO hemolytic disease of the newborn
Usually occurs in a type O mother with a type A or B fetus.
Can occur in a first pregnancy as maternal anti-A and/or anti-B IgG antibodies may be formed prior to pregnancy
Does not worsen with future pregnancies.
Presents as mild jaundice in the neonate within 24 hours of birth
Treatment is phototherapy or exchange transfusion
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Hemoglobin electrophoresis
On a gel, hemoglobin migrates from the negatively charged cathode to the positively charged anode.
HbA migrates the farthest, followed by HbF, HbS, and HbC.
This is because the missense mutations in HbS and HbC replace glutamic acid ⊝ with valine (neutral) and lysine ⊕, respectively, impacting the net protein charge.
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