: CFU-GM Þ monoblast Þ promonocyte Þ monocyte (takes about 6 days; occurs in bone marrow)
monocyte
Þ macrophage (monos circulate 1-3 days, then enter tissue and differentiate into the various forms of macrophages depending on the tissue (Kupffer cells, osteoclasts, microglial cells, etc)
monocytes are released from the BM as soon as they are ready, there is no reservoir as with PMNs
Abnormalities of Monocytes and Macrophages
(1) Moncytopenia
: defined as monocytes < 300/mm3
causes: aplastic anemia: no monocytes being made
hairy-cell leukemia: B-cell malignancy suppresses monocyte production
glucocorticoid therapy: immune suppression Þ greater susceptibility to infection
(2) Monocytosis
: defined as monocytes > 800/mm3
benign or physiologic: cells may be activated as in immune or inflammatory response; or ‘compensatory’ in neutropenia
malignant: may be leukemia involving the monocyte lineage; or lymphoma involving true histiocytes
(3) Hemotophagocytic syndromes
: hematophagocytosis is usually a non-specific finding
hematophagocytosis lymphohistiocytosis
: pediatric disorder where macs gobble up RBCs, platelets, and other white cells; is not a malignancy, but poor prognosis; may be due to infection or may be familial
: essentially lipid storage disease; inherited ß in lysosomal activity Þ accumulation of glycolipid in monos/macs Þ hepatosplenomegaly, pulmonary disease, skeletal lesions, neuro impairments; there is no increase in circulating macs
Gaucher’s disease
: autosomal recessive deficiency of
b -glucosidase Þ accumulation of glucocerebroside in macs
genetics: chromosome 1, over 40 mutations described;
clinical: hepatosplenomegaly; pulmonary disease,
Ý acid phosphatase, PAS-positive material in macs
treatment: IV glucocerebrosidase (placenta derived - it takes 1 ton of placenta to treat one person/1 year)
Neiman-Pick disease
: autosomal recessive deficiency of sphingomyelinase Þ accumulation of sphingomyelin (duh!)
Lymphopenia: defined as <3000/mm3 in children, <1500/mm3 in adults
caused by: decreased production (immunodeficiency syndromes); increased destruction (HIV infection, irradiation, cytotoxic drugs); increased intestinal lymphatic loss (due to impaired lymphatic gut drainage i.e. Whipples Disease)
Mononucleosis syndromes
(lymphophagocytosis): acute febrile illness characterized by lassitude, pharyngitis, lymphadenopathy, splenomegaly, liver function abnormalities, usually in young adults, abnormal lymphocytosis
Classic Mononucleosis
: EBV infection of B-cells leads to polyclonal expansion and hyperglobulinemia; this leads to a CD8+ T-cell and NK cell response to the EBV antigen expressed on the B-cells
monospot test: tests for the characteristic heterophile antibodies which are IgM which react with animal RBC
EBV infected B-cells are suppressed, but they persist for life; re-activation can occur with immune suppression