Intro to hematopoesis and bone marrow morph wk7w10

Question 1

Erythropoisis

Answer 1

• regulated by erythropoietin, a hormone synthesized by the kidney
• nutrients required include iron, B-12, folate
• normal bone marrow function

Question 2

RBC morphology and disease

1. microcytic
2. macrocytic
3. normocytic with abnormal shapes

Answer 2

1. iron deficiency, thalassemia
2. folate, B12 deficiency
3. hereditary spherocytosis, sickle cell disease

Question 3

clincal presentation of iron deficiency

Answer 3

• fatigue, breathlessness
• pica- persistent compulsive desire to ingest certain food or non-edible items like ice, clay, plaster
• sore mouth, angular stomatitis, palor

Question 4

Megaloblastic anemia

Answer 4

• B12 and folic acid deficiency
• bone marrow hypercellular with increased megablasts
• all hematopoetic lineages show nuclear to cytoplasmic dyssynchrony

- SMEAR= macrocytic anemia, hypersegmented neutrophils

Question 5

Rouleaux formation

Answer 5

• increased paraproteins in the blood
• multiple myeloma

Question 6

agglutination

Answer 6

IgM mediated
Causes include viral infections like Influenza, Mycoplasma
Cold Agglutinin Disease

Question 7

Neutrophils (PMNs)

Answer 7

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.

Question 8

Neutrophil development

Answer 8

myeloblast->promyelocyte->myelocyte->metamyelocyte->band->neutrophil

Question 9

Neutrophils- primary defense against infections

Answer 9

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

Question 10

Basophils

Answer 10

• 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

Question 11

Eosinophils

Answer 11

• 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

Question 12

Lymphocytes

Answer 12

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

Question 13

Monocytes

Answer 13

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

Question 14

Reasons for leukocytosis

1. neutrophila
2. eosinophila
3. basophilia
4. lymphocytosis

Answer 14

1. neutrophila: bacterial infections, heat stroke, stress neutrophilia, drugs, steroids, hereditary neutrophilia
2. eosinophila: parasitic infections, allergies, lymphoma, cancers
3. basophilia: CML
4. Lymphocytosis: TB, viral infections, pertussis, infectious mononucleosis
5. Monocytosis: chronic infections, lupus, ulcerative colitis, malaria

Question 15

Plasma Cells

Answer 15

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

Question 16

Multiple Myeloma

Answer 16

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

Question 17

Platelets

Answer 17

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 **

Question 18

Platelet deveopment

Answer 18

hematopoietic stem cell->promegakaryocyte->megakaryocyte->platelets released

Question 19

Thrombocytopenia diseases

Answer 19

DIC- disseminated intravascular coagulation

TTP- thrombotic thrombocytopenic purpura
ITP- immune thrombocytopenia

Medications- heparin, antibiotics, H2 blockers

Bonemarrow Aplastic Anemia, Leukemia, MDS(myelodysplastic syndrome)

Question 20

Thrombocythemia diseases

Answer 20

Primary- Myeloproliferative process- CML, PV, ET

Secondary- acute phase reactant, iron deficiency, acute blood loss, post splenectomy, steroids, epinephrine, chronic infections

Question 21

Clinical findings of platelets

Answer 21

Petechae and purpura

History of easy or spontaneous bruising

Mild to moderate mucosal membrane bleeding
- Gingival bleeding, menorrhagia, epistaxis

Question 22

Normal count but loss of platelet function

causes

Answer 22

Uremia- renal failure

Liver disease

Prosthetic valves

Aspirin or NSAIDs or other drugs (many!)

Congenital (intrinsic platelet defects)- Bernard Soullier syndrome, Glanzmann’s thrombasthenia