Week 4: Macrocytic Anemia Macrocytosis Macrocytosis Vitamin B12 Vitamin B12 Folic acid Folic acid Megaloblastic changes Megaloblastic changes Pernicious anemia Pernicious anemia Schilling test Schilling test Hypersegmented PMN Hypersegmented PMN Bone marrow analysis WBC precursors Liver disease Polycythemia and erythremia PV Newborn CBC

Bone Marrow Analysis Aspirate Aspirate  Particles in fluid part of marrow  Differential count Biopsy Biopsy  Solid part of the marrow  Cellularity Clot section Clot section

AspirationBiopsy

WBC Precursors Myeloblast Myeloblast Promyelocyte Promyelocyte  Primary azurophilic granules Meylocyte Meylocyte  Specific granules Metamyelocyte Metamyelocyte Band, stab Band, stab Segmented neutrophil, PMN Segmented neutrophil, PMN

Myeloblast Promyelocyte Neutrophilic Myelocyte

Segmented neutrophil and lymphocyte

Mast cell and histiocyte Megakaryocyte Plasma cell Mast cell

Histiocyte Fat cell Macrophage

Osteoclasts Giant cellOsteoblasts

Non-Megaloblastic Macrocytosis Alcoholism Alcoholism  Poor nutrition  Cirrhosis Liver disease Liver disease Reticulocytosis Reticulocytosis  Hemolytic anemia  Hemorrhage

Megaloblastic Anemia Hemolytic changes Hemolytic changes Waxy pallor Waxy pallor Neurologic changes with B12 deficiency Neurologic changes with B12 deficiency Glossitis, beefy red or smooth pale tongue Glossitis, beefy red or smooth pale tongue

Causes of Megaloblastic Anemia Folate deficiency Folate deficiency  Dietary (green leafy vegetables)  Malabsorption B12 deficiency B12 deficiency  Dietary  Fish tapeworm (D latum) Pernicious anemia Pernicious anemia  Lack of gastric intrinsic factor (IF) for absorption

B12 Metabolism Bind to cobalophilin (cobalamine binding protein) in saliva and gastric secretion Bind to cobalophilin (cobalamine binding protein) in saliva and gastric secretion Bind to IF (from parietal cell) in the duodenum Bind to IF (from parietal cell) in the duodenum Cbl-IF complex bind to receptor (cubilin) at distal ileum for mucosal absorption Cbl-IF complex bind to receptor (cubilin) at distal ileum for mucosal absorption 1% B12 can be absorbed without IF (megadose of B12 for IF deficiency, no need for IV) 1% B12 can be absorbed without IF (megadose of B12 for IF deficiency, no need for IV)

Autoimmune mechanism for PA

Megaloblastic Lab Changes MCV up to 140 fL MCV up to 140 fL Howell-Jolly bodies and Cabot rings Howell-Jolly bodies and Cabot rings Hypersegmented PMN Hypersegmented PMN Pancytopenia Pancytopenia BM with low M:E ratio BM with low M:E ratio Megaloblastic morphology (giant bands and metas) B12 and folate assays RBC folate (long term indicator) IF antibody (PA) Schilling test (obsolete)

Megaloblastic anemia Megaloblastic BM Hypersegmented PMN

Other Apparent Macrocytoses Cold agglutinin Cold agglutinin  Prewarm samples Hyperglycemia Hyperglycemia  Osmotic changes Clot Clot Rouleaux Rouleaux

Polycythemia Vera A type of myeloproliferative disorder (MPD) A type of myeloproliferative disorder (MPD) Independent of EPO Independent of EPO High total RBC mass (by radio tagging) High total RBC mass (by radio tagging)

Secondary Polycythemia Dehydration (decreased plasma volume) Dehydration (decreased plasma volume) Increased O 2 demand (e.g., emphysema, high elevation) Increased O 2 demand (e.g., emphysema, high elevation) High EPO (e.g., kidney tumor) High EPO (e.g., kidney tumor)