Intro to hematopoesis and bone marrow morph wk7w10 Flashcards
Erythropoisis
- regulated by erythropoietin, a hormone synthesized by the kidney
- nutrients required include iron, B-12, folate
- normal bone marrow function
RBC morphology and disease
- microcytic
- macrocytic
- normocytic with abnormal shapes
- iron deficiency, thalassemia
- folate, B12 deficiency
- hereditary spherocytosis, sickle cell disease
clincal presentation of iron deficiency
- fatigue, breathlessness
- pica- persistent compulsive desire to ingest certain food or non-edible items like ice, clay, plaster
- sore mouth, angular stomatitis, palor
Megaloblastic anemia
- B12 and folic acid deficiency
- bone marrow hypercellular with increased megablasts
- all hematopoetic lineages show nuclear to cytoplasmic dyssynchrony
- SMEAR= macrocytic anemia, hypersegmented neutrophils
Rouleaux formation
- increased paraproteins in the blood
- multiple myeloma
agglutination
IgM mediated
Causes include viral infections like Influenza, Mycoplasma
Cold Agglutinin Disease
Neutrophils (PMNs)
Life span is 5.4 days. Neutrophils play an important role as the first line of defense in bacterial infections
Primary granules- MPO, elastase, defensins, cathepsins
Secondary granules- lactoferrin
Tertiary granules- cathepsin, gelatinase
Granulocytes spend 9 days in the marrow, 3-6 hours in the blood and 1-4 days in the tissues.
Neutrophil development
myeloblast->promyelocyte->myelocyte->metamyelocyte->band->neutrophil
Neutrophils- primary defense against infections
Phagocytosis
Secretion of anti- microbial agents
Neutrophil extracellular trap (NET)- release fiber like material that forms a web around the organisms and kill them extracellularly
Basophils
- affinity for basic dyes
Least common of the granulocytes representing 0.01- 0.3% of white cells
They have receptors that bind to IgE immunoglobulin that is involved in parasitic infections and allergies.
Contains granules with histamine, heparin, elastase, proteoglycans that are released during inflammatory response to parastiic infections and allergens such as pollen, helminths
Basophilia – increased basophils can be seen in chronic myeloid leukemia
Eosinophils
- affinity for acidic dyes
- Constitute 1-6% of the total white cells. Life span of 8-12 hours in circulation
- Involved in allergies and infections (parasitic)
- Secrete numerous leukotriens cytokines and mediators of allergic response, asthma pathogenesis
Lymphocytes
Mononuclear cells-
T-cell – thymus derived cells ,cellular immunity,T-helper cells- CD4
T-suppressor cells- CD8
B-cells- bone marrow derived, humoral immunity ( secrete antibody)
NK- cells- Natural killer cells
Lymphopenia- HIV , reduced CD4 counts
Lymphocytosis- Leukemia/ lymphomas
Monocytes
Replenish the macrophage dendritic system
Inflammation-
- Phagocytosis
- Antigen presentation activating the complement pathway
- Cytokine production
Mononuclear cells with a kidney shaped nucleus and pale blue cytoplasm with vacuoles
Reasons for leukocytosis
- neutrophila
- eosinophila
- basophilia
- lymphocytosis
- neutrophila: bacterial infections, heat stroke, stress neutrophilia, drugs, steroids, hereditary neutrophilia
- eosinophila: parasitic infections, allergies, lymphoma, cancers
- basophilia: CML
- Lymphocytosis: TB, viral infections, pertussis, infectious mononucleosis
- Monocytosis: chronic infections, lupus, ulcerative colitis, malaria
Plasma Cells
Originate in the bone marrow and are terminally differentiated B-lymphocytes
Plasma cells secrete abundant immunoglobulins and play an important role in humoral immunity
Usually not circulate in the peripheral blood
Multiple Myeloma
Multiple Myeloma – Neoplasm arising from malignant plasma cells. It affects the bone marrow and the normal hematopoetic elements are replaced by malignant plasma cells.
The neoplastic plasma cells secrete paraproteins which causes kidney problems and interferes with the normal antibody secretion by plasma cells.
Hence patients are prone to cytopenias due to bone marrow involvement, renal failure and accumulation of paraproteins in abnormal sites leading to functional defect.
Clinical features of MM is CRAB: calcemia, renal failure, anemia , bone lesions
Platelets
Platelets are cytoplasmic blebs arising from the megakaryocyte.
The normal life span of platelets is 7-10 days.
Normal platelet count 150-350,000.
The hormone responsible for platelet production is thrombopoetin produced by the **liver and kidney **
Platelet deveopment
hematopoietic stem cell->promegakaryocyte->megakaryocyte->platelets released
Thrombocytopenia diseases
DIC- disseminated intravascular coagulation
TTP- thrombotic thrombocytopenic purpura
ITP- immune thrombocytopenia
Medications- heparin, antibiotics, H2 blockers
Bonemarrow Aplastic Anemia, Leukemia, MDS(myelodysplastic syndrome)
Thrombocythemia diseases
Primary- Myeloproliferative process- CML, PV, ET
Secondary- acute phase reactant, iron deficiency, acute blood loss, post splenectomy, steroids, epinephrine, chronic infections
Clinical findings of platelets
Petechae and purpura
History of easy or spontaneous bruising
Mild to moderate mucosal membrane bleeding
- Gingival bleeding, menorrhagia, epistaxis
Normal count but loss of platelet function
causes
Uremia- renal failure
Liver disease
Prosthetic valves
Aspirin or NSAIDs or other drugs (many!)
Congenital (intrinsic platelet defects)- Bernard Soullier syndrome, Glanzmann’s thrombasthenia
