- Clinical science
Hematology is the study of blood and the disorders related to it. Human blood is composed of ∼45% cellular components and ∼55% plasma. Blood has many functions, including transporting oxygen, regulating body temperature, and supporting the immune system. The cellular component consists of three major cell types, all of which arise from located primarily in the bone marrow: red blood cells (RBCs), white blood cells (WBCs), and platelets. Red blood cells (RBC, erythrocytes) are hemoglobin-carrying cells that primarily transport oxygen. White blood cells (WBC, leukocytes) take the form of either granulocytes or lymphocytes. Granulocytes are part of the innate immune system and play a key role in the immune response to bacteria, fungi, and parasites. Lymphocytes are highly antigen-specific, meaning they are able to target specific infectious agents, primarily viruses. Platelets are the other major cellular component of blood and are small anucleate cells produced from megakaryocytes in the bone marrow. This learning card provides an overview of the production, morphology, and most important functions of blood cells.
Function of blood
- Transports oxygen, nutrients, metabolic waste products
- Regulation of body temperature, signal transmission, acid-base homeostasis, and immune response
Composition of blood
- 60–80 mL blood/kg body weight ≅ 5 L blood for an adult weighing 70 kg/154 lbs
- 45% cellular components (→ hematocrit), 55% plasma
Production of blood
- Location: bone marrow; the spleen and liver are the primary sites before birth
- Hematopoietic stem cells can differentiate into any type of blood cell and give rise to all blood cells through the following two precursor cells:
- Left shift (or blood shift): an increase in immature precursor cells; (e.g., increase in band neutrophils with rod-shaped nuclei in response to acute inflammation) in the blood. In most cases, infection is the cause of a left shift.
- A reactive increase of a cell line ends in "-cytosis" (e.g., leukocytosis); neoplastic increase is referred to as "-emia" (e.g., leukemia).
Bone marrow is the spongy, soft tissue that fills the hollow spaces within cancellous (spongy) bone. It is composed of stromal cells and stem cells, which are the progenitors of all five blood cell lineages. Hematopoiesis is the main function of the bone marrow. It also filters aging RBCs and houses immune cells (e.g., plasma cells).
|Red marrow||Yellow marrow|
Stromal cells do not participate in the process of hematopoiesis. However, they play a critical role in maintaining and regulating the process. These cells remove potentially harmful cells or products (e.g., self-reactive cells by clonal deletion).
|Adventitial reticular cells|
|Mesenchymal stem cells|
Growth factors for hematopoiesis
|Stem cell factor|| || |
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|Thrombopoietin|| || |
Erythropoiesis: red blood cell (RBC, erythrocyte) production
- Location: red bone marrow; before birth, the spleen and liver are the primary site of production
- Duration: : Production and maturation of RBCs takes about 1 week.
- Regulation: primarily (EPO); as well as other hematopoietic growth factors, including; granulocyte-macrophage colony-stimulating factor (GM-CSF); , stem cell factor (SCF), and interleukin 3 (IL-3).
|Stages of RBC differentiation||Causes of erythropoiesis pathology|
|RBC precursor cells|| |
Life span: about 120 days; enter peripheral blood as reticulocytes
- Peripheral reticulocytes indicate active erythropoesis
- Circulating reticulocytes are identified by the presence of cytoplasmic ribosomal RNA which stains with methylene blue
- Oxygen and CO2 transport
- Buffering in acid-base homeostasis
- Impaired in hemolytic anemia
- Generate ATP exclusively from glycolysis
- Reference range: ♂ 13.5–17.5 g/dL; (2.09–2.71 mmol/L); ♀ 12–16 g/dL (1.86–2.48 mmol/L)
- Clinical significance: ↓ , ↑
Hb level is composed of the following components:
- Cellular component of blood (erythrocytes account for 99% HCT)
- Reference range: ♂ 41%–53%; ♀ 36%–46%
|Mean corpuscular volume (MCV)||Average volume of each RBC||81–100 fL (normocytic)||Macrocytic RBCs (e.g., in vitamin B12 deficiency)|
|Mean corpuscular hemoglobin (MCH)||Average mass of hemoglobin in each RBC||27–34 pg (normochromic)||Hyperchromic RBCs (e.g., in vitamin B12 deficiency)|
|Mean corpuscular hemoglobin concentration (MCHC)||Calculated as hemoglobin/hematocrit: mean hemoglobin concentration of all RBCs||30–36 g/dL||Possibly in iron deficiency, thalassemia||E.g., in spherocytosis|
|Absolute Reticulocyte count||The percentage of all erythrocytes that are reticulocytes. Represents erythropoietic activity.||0.5–1.5%||Insufficient erythropoiesis (e.g., aplastic anemia)||Increased erythropoiesis (e.g., secondary to hemolysis or blood loss)|
|Corrected reticulocyte count (RI)||Absolute reticulocyte count × (patient hematocrit/normal hematocrit )||1-3%|
|Reticulocyte production index (RPI)||In anemia: > 3 normal, < 2 inadequate|
|Red blood cell distribution width (RDW)||Measure of the variation in the volume of red blood cells||13%–15%||Increased variation in size (called anisocytosis) is a result of conditions that decrease RBC production (e.g. , , ).|
- Leukocytes are classified as either:
|Leukocytosis|| || |
White myeloid blood cell (leukocyte) production
- Location: bone marrow
- Duration: variable
- Stages of granulopoiesis: pluripotent hemopoietic stem cell → common myeloid precursor cell → myeloblast → promyelocyte → eosino/neutro/basophilic myelocyte → metamyelocyte → band cell → granulocytes (eosino/neutro/basophil)
- Stages of monocyte development: pluripotent hemopoietic stem cell → common myeloid precursor cell → myeloblast → monoblast → promonocyte → monocyte
- Stages of mast cell development: pluripotent hemopoietic stem cell → common myeloid precursor cell → mast cell
- Lifespan: variable
- Function: See table below.
- Blood concentration: 2400–6900/μL
|Neutrophil granulocyte (neutrophil)|
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Lymphopoiesis (lymphocyte production)
T cells mature in the thymus (absent in ).
- Positive selection
- Negative selection
- B cells mature in the bone marrow.
- Mature cells migrate to lymph nodes.
- T cells mature in the thymus (absent in ).
- Somatic recombination: random recombination of gene segments coding for lymphocyte receptors that enables a cell to specialize in responding to a specific antigen
- Central tolerance: apoptosis induced in autoreactive cells (respond to self-antigens)
- Mature lymphocytes circulate through the bloodstream, migrate into tissue, and return to the blood via lymphatic vessels.
- Peripheral tolerance: Mature cells that respond to self-antigens become anergic (lose their function) or undergo apoptosis.
- Abnormal lymphocyte concentration: See table below.
|Lymphocytosis||Increase in number of lymphocytes in the blood to > 4000/μL (absolute) or > 50% of all leukocytes (relative)|
|Lymphocytopenia (lymphopenia)||Decrease in number of lymphocytes in the blood to <1000/μL (absolute) or < 20% of all leukocytes (relative)|
NK cells arise from lymphoid precursor cells, but receptors can be activated with or without binding antibodies or a major histocompatibility complex.
Detection and destruction of cells that do not express MHC-I receptors
- Cells infected with viruses (especially herpes viruses)
- Tumor cells
- Kill via
- Induction of apoptosis (granzymes, perforin)
- Antibody-dependent cell-mediated cytotoxicity (activated by binding of CD16)
- Cytokine production: INF-γ and TNF-α
- Function enhanced by IFN-α and IFN‑β, IL-2, IL-12
- Detection and destruction of cells that do not express MHC-I receptors
- T-cell receptor: a complex of proteins of the immunoglobulin superfamily, which binds antigen bound to major histocompatibility complexes on other cells
|Subpopulations||Important surface markers||Function|
|CD8 positive||Recognize foreign (mostly viral) antigens presented via MHC-I and, depending on the scenario, trigger apoptosis or cell lysis of the presenting cell|
|T-helper cells They require antigen presenting cells equipped with MHC-II receptors → recognize presented antigens → cytokine release||TH1 cells||CD4 positive||Initiate the cellular immune response → macrophage stimulation|
|TH2 cells||Initiate humoral immune response in cooperation with B lymphocytes → immunoglobulin production|
|TH17 cells||Tissue inflammation, both pro- and anti-inflammatory|
|Regulatory T cells (Tregs, suppressor T cells)||Limit and protect against excessive immune response|
|Memory T cells||CD4 & CD8 positive||Conservation/memory of a specific acquired immune response|
- CD4/CD8 quotient Some diseases can be characterized by either an increase or decrease in CD4 lymphocytes compared to CD8 lymphocyte levels.
- Part of the
- Important surface marker: CD20
- The surface of B lymphocytes contains B-cell receptors that are highly specific to certain antigens.
If a naive B-cell receptor is presented with an antigen, the B cell is activated and migrates to the germinal center of a lymph node or the spleen.
- Further development
- Activation is triggered.
- If a naive B-cell receptor is presented with an antigen, the B cell is activated and migrates to the germinal center of a lymph node or the spleen.
- Definition: : an absence of granulocytes; (i.e., an absolute neutrophil count (ANC) of zero); may also be used to refer to severe neutropenia
Etiology and pathophysiology:
Drug-induced agranulocytosis (∼ 70% of cases):
- Immune-mediated mechanism (type II hypersensitivity reaction)
- Drug toxicity mechanism: direct damage to myeloid precursors
- MNEMONIC: Causes Pretty Major Collapse To Defense Cells – Clozapine, Propylthiouracil, Methimazole, Carbamazepine, Ticlopidine, Dapsone, Chloramphenicol
- Antithyroid drugs: ; , , ,
- Antiinflammatory drugs: sulfasalazine, NSAIDs
- Antibiotics: t; , dapsone
- Antipsychotic drugs:
- Anticonvulsants: ; , , ,
- Cardiovascular drugs: antiarrhythmics (, flecainide), ticlopidine
- Antifungal agents: , flucytosine
- Drug-independent agranulocytosis (∼ 30% of cases)
- Drug-induced agranulocytosis (∼ 70% of cases):
- Clinical presentation: triad of aphthous stomatitis, sore throat , and fever
- Treatment (of drug-induced agranulocytosis):
- Monitoring of the white blood cell count and differential after starting such drugs as clozapine
- Location: bone marrow
- Duration: Production and maturation of platelets takes about 1 week.
- Regulation: Thrombopoietin (secreted by the liver and kidneys) stimulates megakaryocyte proliferation and maturation in the bone marrow.
- Stages of thrombopoiesis: myeloid precursor cell → megakaryoblasts → megakaryocytes → platelets
- Function: : forms plug in bleeding vessel (primary hemostasis)
- Lifespan: circulation for 8–9 days
Concentration: 150,000 to 450,000/μLcells
- Abnormal platelet production: See table below.
|Thrombocytosis||Increase in number of platelets to > 400,000/μL (absolute)|
|Thrombocytopenia||Decrease in number of platelets to < 150,000/μL (absolute)|| |