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.
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
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%)
2 mins
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.
Monocyte
- Differentiates into macrophage in tissues
- Large, kidney-shaped nucleus (Image)
- Extensive “frosted glass” cytoplasm.
- Found in blood
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
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
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
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.
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.
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
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).
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
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
Fetal Erythropoiesis
- YOLK SAC
- 3–8 weeks
- Liver
- 6 weeks–birth
- Spleen
- 10–28 weeks
- Bone marrow
- 18 weeks to adult
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.
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
2 mins
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.
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
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.
