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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