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Nutrients necessary for RBC maturation are
DeficientMegaloblastic Anemia
Iron Deficiency Anemia
Aplastic Anemia
Anemia of Renal Disease
Anemia of Chronic Disease
Myelopthisic Anemia
Anemia Caused by Lead Poisoning2
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Ineffective DNA synthesis
Impaired nuclear development
Megaloblast
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Vit B12 or Folate
Deficiency
Chemotherapeutic
Agents
Inherited Defects
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Decreased intake◦ Inadequate intake, Vegetarians
Increased Requirement◦ Pregnancy
◦Hyper thyroidism
◦Disseminated Cancer
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Impaired Absorption◦ Intrinsic Factor Deficiency
PERNICIOUS
GASTRECTOMY
◦ Malabsorption states
◦ Diffuse Intestinal Disease
◦ Ileal resection, ileitis
◦ Parasites – hook/tapeworms
◦ Bactrial overgrowth in Blind Loops
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More in Scandinavian & English Speaking
Blacks & Hispanics in US
Common in OLD Age 50’s-80’s
Maybe Strong Genetic predisposition
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Immune – mediated destruction of gastric mucosa
Autoreactive T-cell response initiates autoAbprod’n.
Result to Chronic atrophic gastritis
Types of AutoAb◦ 75%Type I – Blocks binding of B12 to IF
◦ Type II – Prevent Binding of IF - B12 to IlealReceptor
◦ Type III – Not specific, common in elderly not R/T pernicious
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Insidious onset
Progressive anemia
Atrophic glossitis & Gastric atrophy◦ Seen in pernicious anemia
◦ Intestinalization of gastric epithelium Gastric Ca
CNS in ¼ of cases◦ Spastic paraparesis Sensory ataxia
◦ Severe paresthesia in the L.E.
Tx by giving oral / parenteral B12◦ Halt progression of Neuro s/s but not GI changes
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Moderate – Severe Megaloblastic Anemia
Leukepenia & Thrombocytopenia
Mild Jaundice – peripheral hemolysis of rbc
Neurological – Posterolateral spinal tracts
Schillings test – Decreased uptake of radioactive B12
Low B12
Elevated Homocysteine & Methylmalonic acid◦ More Sensitive than B12
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Manifestation same as B12 Deficiency◦ Except Neurological s/s
Folic acid is sensitive to heat, boiling, frying, steaming ◦ Brocolli, lettuce, asparagus, lemons, banana
Casues:1. Decreased intake
2. Increased requirement
3. Impaired use
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Decreased intake Increased Requirement
Impaired Use
1.INADEQUATE INTAKE- Chronic Alcoholics - Elderly
1. Pregnancy2. Infancy3. Hemolytic anemia4. Disseminated Cancer
FOLATE ANTAGONIST DRUGS
- Chemotherapeuticdrugs
- Damage or Inhibit
DNA synthesis- Affect rapidly
dividing cells
2. IMPAIRED INTESTINAL ABSORPTION
- TROPICAL SPRUE, - SI ymphoma- Drugs – oral
contraceptives- phenytoin
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Pancytopenia- intramedullary destruction of precursor( apoptosis )
Macrocytes (+) – high MCV but not MCHC◦ Thicker , Well – Hemoglobinized
◦ No Central pallor
Retic – Low
Large & Hypersegmented Neutrophils
BM markedly Hypercellular with Asynchronous maturation of N/C
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Most common nutritional disorder in the world.
Prevalence of iron deficiency anemia is
◦ Higher in the developing countries,
◦ Toddlers & adolescent girls
◦ Women of childbearing age
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Balance : 1 mg iron absorbed / day
Daily iron requirement :◦ 7-10mg (men ) 7-20mg ( women )
◦ Ascorbic acid , Citric acid, Amino acids enhance absorption
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Iron absorbed by duodenum & Jejunum transported by Transferrin Liver & BM Incorporated to Developing rbc in BM
Iron is stored as Hemosiderin( aggregates ) or Ferritin ( complexedwith Apoferittin )
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◦ Inadequate dietary iron
◦ Pregnancy , Lactation
◦ Chronic blood loss – GIT bleeding or tumors
Most common cause in Western countries
◦ Impaired absorption
◦ Menstrual , parturition, Vaginal Bleeding
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Morphology: Clinical Manifestation:
BM – mild to moderate erythroid hyperplasia◦ Dxtic : Disappearance of
stainable iron in macrophages in BM ( Prussian Blue Stain )
Microcytic Hypochromicrbc
Pencil rbc Anisopoikilocytosis No Reticulocytosis Low Serum Ferritin High TIBC
Anemia Severe Cases:
◦ GLOSSITIS, ANGULAR STOMATITIS, KOILONYCHIA
Treatment:◦ Iron Supplement
◦ Treat the cause
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Disorder of Pleuripotential stem cell
Lead to BM failure Pancytopenia
Most are Idiopathic
Other Causes:◦ Radiation – whole body, dose dependent
◦ Chemotx
◦ Immune reaction due to viral infxn
◦ Idiosynchratic reactions- dose independent
Chloramphenicol
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Immunologically mediated suppression
Stem cells drugs, infectious agent
environmental insults
Genetically Altered stem cell
1. Evokes a T cell-mediated immune response (IFN-gamma and TNF-alpha)
POTENT INHIBITOR OF STEM CELL FUNCTION
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2. Give rise to clonal population with reduced proliferative capacity
APLASTIC ANEMIA
Either pathway
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BONE MARROW
GRANULOCYTOPENIA
THROMBOCYTOPENIA
INJURY TO OTHER
ORGANS
•HYPOCELLULAR
•DRY TAP
•BACTERIAL INFN
•BLEEDING
•LIVER, KIDNEYS
etc.
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Unpredictable◦ Recovery if w/draw toxic drugs in some
Allogenic BM transplant
Immunosuppressive therapy◦ Antithymocyte Globulin
◦ Cyclosporine
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ANEMIA TYPE DESCRIPTION BONE MARROW BLOOD
Anemia of Renal Dse
Erythropoeitin Lack of ErythroidPrecursor
NormocyticNormochromic
rbcBurr Cells+ Schistocytes
Anemia of ChronicDisease
Block in the use ofStorage iron
MalignancyChronic Inflam.
Increased Iron Stores in
Macrophages
Mild – ModerateNormocytic to Microcytic
Anemia
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MyelopthisicAnemia
Bone marrow Infiltration
Infiltration by processes such as
Carcinoma / Granulomas
NormocyticAnemiaTeardrop rbcImmature
GranulocytesN-rbc
Anemia of Lead Poisoning- Ingestion of
lead paint orexposure
Hgb Synthesis Ringed Sideroblast(Impaired iron use by rbc precursors )
MicrocyticHypochromicrbc
Basophilic Stippling
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POLYCYTHEMIA32
Abnormally high rbc and Hgb
Type:1. RELATIVE – HEMOCONCENTRATION
DEHYDRATION
STRESS ( Gaisbock syndrome)
Patient is Obese, hypertensive , anxious
POLYCYTHEMIA33
2. ABSOLUTE
Primary A. Intrinsic Abn of myeloid stem cells
Polycythemia vera
B. Mutation in erythropoietin receptor
Cause Hyperresponsiveness to eryhtropoietin
POLYCYTHEMIA34
SecondaryHigh eryhtropoietin
Appropriate - Adaptive
Inappropriate secretion of hormone
Liver/ Renal Cell Ca