Leukocytosis. Leukopenia. The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation  Department of Pathophysiology Leukocytosis. Leukopenia. Lecture presentation Professor Pirozhkov S.V. 2015-2016 education year

Pluripotent stem cell of hematopoiesis Scheme of hematopoiesis Lymphocyte Lymphoid stem cell Erythrocyte Erythroblast CFU eryth. Pluripotent stem cell of hematopoiesis Myeloblast Neutrophil CFU g/m Monoblast Мonocyte Myeloid stem cell CFU eosin. Eosinoblast Eosinophil CFU basoph. Basophiloblast Basophil Platelets CFU mega. Megakaryoblast Megakaryocyte

Stages of neutrophilic myelopoiesis Cell Stage Characteristics Myeloblast The nucleus with the nucleoli Large cell, primary granules appear Promyelocyte Myelocyte Secondary granules appear Metamyelocyte Bean-like nucleus Band Condensed neutrophil band-like nucleus Segmented Condensed neutrophil segmented nucleus

Composition of granules in neutrophils ■ Primary (azurophil) granules: myeloperoxidase lyzozyme cationic protein acid hydrolase elastase nonspecific collagenase defensines cathepsin G phospholipase А2 ■ Secondary (specific) granules: lactoferrin alkaline phosphotase collagenase type IV leukocyte adhesive molecules plasminogen activator AG

Functional disorders of leukocytes DISORDERS OF THE LEUKOCYTE SYSTEM QUANTITATIVE QUALITATIVE Leukocytosis Leukopenia Functional disorders of leukocytes > 9*109 cells/L of blood < 4*109 cells/L of blood Nuclear shifts

Types of leukocytosis based on their biological significance Physiological Pathological Protective/adaptive Functional

Leukocytosis MECHANISMS OF LEUKOCYTOSIS Mobilization from the marginal pool in the vessels (demargination) Increased mobilization from the bone marrow pool Stimulation of leukopoiesis Hemoconcentration “True” leukocytosis “False” leukocytosis

Causes of the stimulation of hematopoiesis ● Infection causes by: bacteria fungi viruses (less commonly) ● Inflammatory process: burns acute myocardial infarction allergy vasculitis ● Myeloproliferative diseases

Types of nuclear shift to the left ◙ Hyporegenerative: increase in band neutrophils in the peripheral blood > 6% slight leukocytosis in the range of 10-11*109/l ◙ Regenerative: increase in band neutrophils and emergence of metamyelocites moderate leukocytosis in the range of 13-18*109/l ◙ Hyperregenerative: considerable increase in band neutrophils, large amount of metamyelocytes, emergence of myelocytes leukocytosis in the range of 20-25*109/l

Causes of increased mobilization of leukocytes from the marginal pool in the vessels (demargination) ► Use of medicines: epinephrine glucocorticoids non-steroidal untiinflammatory drugs ► Psychological and physical stress ►Hereditary deficit of adhesive molecules on the surface of leukocytes

Basophilia - > 0.2*109 basophils/l of blood ● occurs rarely, usually indicates the presence of myeloproliferative disease Monocytosis - > 1*109 monocytes/l of blood ● chronic infection (tuberculosis etc.) ● bacterial endocarditis ● rickettsiosis, malaria ● vasculitis (SLE etc.) ● inflammatory diseases of the intestine (ulcerative colitis) Lymphocytosis - > 4*109 lymphocytes/l of blood ● accompanies monocytosis in many diseases associated with chronic stimulation of the immune system (tuberculosis, brucellosis etc.) ● viral infections (HAV, Epstein-Barr virus, cytomegalovirus)

Leukopenia МECHANISMS OF LEUKOPENIA Intense destruction of leukocytes in the circulation or hematopoietic organs Redistribution in the vessels Impairment of leukopoiesis Hemodilution Increased utilization of leukocytes or loss in the external media “False” leukopenia “True” leukopenia

Manifestations and negative consequences of neutropenia ● Malaise, fever ● Weakness, fatigue ● Severe infections (when the leukocytes counts < 0.5*109/l) ● Ulcerative-necrotic lesions of the mucous membrane of the gingivae, oral cavity and pharynx (agranulocytic pharyngitis) ● Skin infection – small superficial pyogenic abscesses (furunculosis), bacterial invasion of the dermis (cellulitis)

Disorders of the function of granulocytes/monocytes: Abnormal adhesion/aggregation Abnormal microbicidal activity, processing and presentation of antigens Abnormal chemokinesis/chemotaxis or ability to change shape (deformability)