• stem cells
• GF's
• microenvironments

tightly regulated

• self renewal
• differentiation

• during fetal life
  • starts with yolk sac
  • then liver and spleen for second trimester
• begining in second trimester, bone marrow hematopoiesis begins to rise and peaks at birth, then:
  • higest in vertebra
  • next highest is sternum
  • thrid highes is rib
  • lowest in tibia and femur (drop off during second decade of life)

• CSF (colony stimulating factors)
• interleukins
• erythropoietin

• erythrocytes
  • 5 days to release
  • 16 progeny from each stem cell
  • survive 120 days
• granulocytic (esp. neutrophils)
  • 14 days to release
  • 16-32 progeny from each stem cell
  • survive 1-4 days
• megkaryocytic
  • 5 days to release
  • hundreds of progeny from each stem cell
  • survive 8-11 days

• specimen types
  • aspirate (can smear or allow it to clot)
  • core biopsy (bone sample)
• sites
  • posterior, superior iliac spine
  • sternum (aspirate only)
  • anterior tibia (young kids)

• marrow cellularity (estimate only)
• myeloid:erythroid ratio- normal 3:1
• maturation of hematopoietic lineage
• low frequency elements- plasma cells, histiocytes, lymphocytes (found in small numbers)
• iron stores- histiocytic and sideroblastic
• foreign cells (metastatic neoplasm)
• microorganism

• cellularity- in young children, 90% or in elderly, 30%
• general maturation of hematopoetic lineage (aspirate is better)
• fibrosis
• foreign cells
• granulomas
• microorganisms- esp. mycobact., fungi
• bone morphology

• anemia, neutropenia, thrombocytopenia
• leukemia evaluation
• metastatic neoplasm
• selected infectious agents

after less invasive tests have been exhausted

• decreased Hct
• decrease Hb conc.
• decrease RBC count

• gender (after puberty, higher in male)
• age (higher in newborn, low in children, then pop to adult levels in puberty)
• high altitude living (decrease oxygen tension induce increase erythropoietin production)
• posture (prolong bed rest decrease values)
• stress, extreme exercise- increase values
• dehydration- increase values (hemoconcentration)
• overhydration (ex: IV fluids)- decrease values (hemodilation)

pathophys

morphologic

• decrease RBC production
• increase RBC destruction (hemolytic anemia)
• increase RBC loss (acute hemorrhage)

• primarily affect stem cells
  • aplastic anemia
  • pure red cell aplasia (only RBC effected)
  • myelodysplastic syndrome
  • anemia of renal failure (EPO deficiency)
• afect differentiating cells
  • impair DNA synthesis
    • B12 or folate deficiency
    • impair B12, folate metabolism
  • impair Hb synthesis
    • iron deficiency
    • thalassemia (decrease globin chain syn.)
    • sideroblastic anemia (defective heme synthesis)
  • multiple mechanism
    • anemia or chronic disease
    • myelophthisic anemia (space occupying disease of bone marrow)

• extracorpuscular
  • immune mediated
  • non immune mediated
• intracorpuscular
  • acquired
  • inherited
    • RBC membrane defects
    • RBC enzyme deficiencies (G6PDH)
    • globin chain structural defects
    • globin chain synthesis defects

• normocytic
• microcytic
• macrocytic

• aplastic anemia
• anemia of chronic disease (some)
• myelophthisic anemia
• hemolytic anemia (most EXCEPT thalessthemia)
• acute blood loss

• iron deficiency
• thalassemia
• sideroblastic anemia
• anemia of chronic disease (some)

• B12 or folate deficiency
• certain antineoplastic drugs

• fatigability
• dyspnea on exertion
• faintness
• vertigo
• palpitation
• angina pectoris
• claudication
• tinnitis
• headache

• general features- due to reduced oxygen carrying capacity of blood
  • tissue hypoxia
  • compensatory mechanism to prevent tissue hypoxia
• specific features
  • related to specific etiology of anemia

• pallor
• tachycardia
• hypotension
• systolic murmor

• history of GI or GU bleed- iron deficiency
• PICA (eating unusual things like clay, starchy foods, chew ice)- iron deficiency
• jaundice- hemolytic anemia
• dark urine- hemolytic anemia
• neurologic complaints- B12 deficiency

• dry atrophic skin and nail changes- iron deficiency
• jaundice- hemolytic anemia
• red, swollen tongue- B12 deficiency
• certain neurologic signs- B12 deficiency

• rate at which anemia develops
  • ability to compensate over time
• degree of cardiac or pulmonary compensation
  • young people tolerate better than older
• metabolic requirements
  • increase in metabolic requirements makes anemic patietns worse (ex: pregnancy)
• underlying disease states

• Hct, Hb, RBC count (CBC)
• RBC indices (CBC)
• peripheral smear evaluation
• reticulocyte count
• iron studies
• B12 and folate studies
• Hb degradation products
• specific tests for hemolytic anemia
• bone marrow examination

• WBC count (total)
• WBC differential count (% and absolute counts)
• Hct
• Hb
• RBC count
• RBC indices
  • MCV
  • MCH
  • MCHC
  • RDW
• platelet count

• definition- measure of average volume (size) of individual RBC
• used to classify anemias morphologically

• measure of average total Hb content of individual RBC
• parallel MCV and MCHC

• measure of average concentrations of Hb in individual RBC
• decreased in microcytic anemia

• RBC morphology
  • size- variation (anisocytosis), microcytic, normocytic, macrocytic
• Hb concentration
  • normochromic
  • hypochromic
• number of immature RBC
  • polychromasia (just been released from bone marrow, still got a little too much RNA, so a lil larger and bluer)
  • nucleated RBC's
• shape
  • variation (poikilocytosis)
  • specific shapes

• normal (discocyte)
• target cell (codocyte)
• teardrop cell (dacryocyte)
• fragmented RBC (schistocyte)
• sickle cell (drepanocyte)
• ovalocyte (elliptocyte)
• spherocyte
• burr cell (echinocyte)
• acanthocyte

• platelet number and morphology
• WBC number and morphology

• RBC stained for RNA; immature RBC have residual RNA
• quantitation of number of immature RBC present in peripheral blood
• corrected reticulcyte count
  • corrected reticulocyte count (%) = raw reticulocyte % x (patients Hct/mean normal Hct)

• serum iron
  • total iron present of serum
• total iron binding capacity
  • total capacity of serum to bind iron
  • reflection of serum transferrin level
• serum ferritin
  • reflect total body iron storages

• serum vit B12 (cobalamin)- good reflection of body stores
• serum and RBC folate
  • serum level is labile (reflects recent intake in diet)
  • RBC levels better measure of total body stores
• Schilling test (not done)
  • once useful in det. cause of vit B12
  • difficult for patient and associated with analytical problems
• IF blocking Ab
  • high specificity
  • when positive in patient of low vit B12, dx of autoimmune pernicious anemia

• Coombs test
• RBC enzyme assay for G6PDH
• test for sickeling Hb
• Hb electrophoresis to quantify Hb A2, F
• sucrose hemolysis, HAM's, specific red cell Ag tests for PNH
• osmotic fragility, RBC membrane protein test for hereditary spherocytosis

• amount of erythropoiesis in marrow
  • total cellularity
  • M:E ratio
• erythrocytic maturation sequence
• iron stores
  • histiocytes
  • sideroblastic
• hematopoietic or metastatic neoplasms

1. there is a decrease in partial pressure of oxygen
2. this is sensed by oxygen senser in kidney
3. it will respond by increase production of EPO
4. leads to stimulation of production of only cells committed to RBC linieage