Hematopoiesis and Leukocyte Disorders

what is blood?

main types of blood cells

hematopoiesis- blood cell production

hematopoiesis- bone marrow to circulating blood

neutrophils

-most numerous leukocytes

-polymorphonuclear or “segmented” cells

-primary defense against infections (“pawns”)

-phagocytes

-kill with toxic oxygen species and toxic proteins

bands

-immature neutrophil form

-present in serious infections

-”bandemia” suggests serious infection

-"U-shaped nucleus”

lymphocytes

-second most numerous leukocyte

-pleiform immune functions: antibody production, destroy virus-infected and cancer cells, master coordinators of immune response

lymphocytes

lymphocyte ontogeny

monocytes

-”garbage collectors of the immune system”

-phagocytes that eat: bacteria, senescent cells, tattoos

-antigen presenting cells

-differentiate into macrophages in organs

eosinophil

-minor component of blood

-granules filled with vasoactive compounds

-thought to fight parasites

-mediators of allergy

basophils

-least common leukocyte

-granules contain: heparin, histamine

-normal function unclear

-elevated in hematologic cancers, especially chronic myeloid leukemia

platelets

-anucleate and small

-procoagulant granules

-key components of hemostasis (clotting)

-bind to damaged endothelium via von Willebrand Factor

-production driven by thrombopoietin

thrombopoiesis- platelet production

-megakaryocytes are enormous multinucleated cells in the bone marrow that produce platelets

regulation of platelet production

erythrocyte (RBC)/reticulocyte

-anucleate sacks of hemoglobin

-biconcave disc shape essential to function

-lifespan of 120 days

-production driven by erythropoietin

-reticulocytes: newly released erythrocytes, slightly purple (mRNA), comprise ~1% of RBCs, should increase in anemia

erythropoietin

-regulated erythrocyte production

hematocrit

-one method of determining how many RBCs someone has

-ratio of centrifuged RBCs to total blood volume

-measuring blood hemoglobin concentration is more accurate

mean corpuscular volume (MCV)

-80-100 = normocytic

-<80 = microcytic

->100 = macrocytic

erythrocyte cell membrane and cytoskeleton

-contain many proteins essential to its biconcave disc function

-hereditary spherocytosis

-abnormal cytoskeleton function can cause anemia

-picture actually hereditary elliptocytosis

pathophysiology of spherocytosis/elliptocytosis

-bone marrow

myelopoiesis- WBC production

erythropoiesis- RBC production

complete blood count (CBC)

leukocyte differential

leukopenia

causes of neutropenia

duffy associated neutrophil count

-formerly called “benign ethnic neutropenia”

-inherited absence of Duffy protein on blood cells: protects against endemic malaria in west Africa, causes spurious neutropenia

-major source of endemic racism in hematology: unnecessary hematology referrals and testing, delayed surgeries, exclusion from cancer clinical trials, unnecessary chemotherapy dose reductions

causes of lymphopenia

-HIV/AIDS: hypergammaglobulinemia, lymphocyte count determines AIDS-defining illness risk

-medications: corticosteroids, immunosuppressives and chemotherapy

-viral infections: EBV, CMV

causes of neutrophilia

eosinophilia

-neoplasia

-allergy

-addison’s disease

-collagen-vascular disease

-parasite infection

rare inherited leukocyte disorders (almost never see these)

-lazy leukocyte syndrome

-cyclic neutropenia

-Chediak-Higashi syndrome

-chronic granulomatous disease

-Bruton’s agammaglobulinamia

-severe combined immunodeficiencies

summary