• Clinical science

Basics of hematology

Abstract

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 hematopoietic stem cells located primarily in the bone marrow: red blood cells (RBCs), white blood cells (WBCs), and platelets. Red blood cells (RBC, erythrocyte) are hemoglobin-carrying cells that primarily transport oxygen. White blood cells (WBC, leukocyte) 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.

Introduction

  • 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:
      1. Lymphoid precursor cells: origin of lymphocyte and natural killer cells
      2. Myeloid precursor cells: origin of erythrocytes, granulocytes, and megakaryocytes
    • 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).

References:[1][2][3][4]

Bone marrow

Overview

Bone marrow is the spongy, soft tissue that fills the hollow space within bones. 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 of the bone 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).

Cells Characteristics
Adventitial reticular cells
Mesenchymal stem cells
Macrophages
  • Located around sinusoids, in the extravascular surface of the marrow

Growth factors for hematopoiesis

This section focuses on the effect growth factors and cytokines have on bone marrow. For systemic effects, see the immune system.

Growth factor Characteristics Function
Stem cell factor

Granulocyte-monocyte colony-stimulating factor

(GM-CSF)

  • Produced by endothelial cells and T cells

Granulocyte colony-stimulating factor

(G-CSF)

Monocyte colony-stimulating factor

(M-CSF)

  • Promotes mitosis, differentiation, and activity of monocyte colony-forming units
Erythropoietin
  • Produced by endothelial cells in the peritubular capillaries of the kidney and hepatocytes
Thrombopoietin
  • Primarily produced in the liver
  • Stimulates thrombopoiesis by promoting megakaryocyte colony-forming units

Red cell line - erythrocytes

Erythropoiesis: red blood cell (RBC, erythrocyte) production

Stages of erythropoiesis Causes of erythropoiesis pathology
RBC precursor cells
Proerythroblast
Erythroblast

RBC physiology

Diagnostic parameters

  • Hemoglobin (Hb)
    • 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: ↓ anemia, ↑ polycythemia
    • Hb level is composed of the following components:
      • Heme
      • Globin
        • The globular protein from hemoglobin is a tetramer consisting of 4 individual subunits that bind heme. Between 95–98% of adult hemoglobin (Hb) is HbA1; , which consists of two alpha chains and two beta chains.
        • Clinical significance: thalassemia
Description Reference value Decrease Increase
Mean corpuscular volume (MCV) Average volume of one RBC 81–100 fL (normocytic)

Microcytic RBCs (e.g., iron deficiency)

Macrocytic RBCs (e.g., in vitamin B12 deficiency)
Mean corpuscular hemoglobin (MCH) Average hemoglobin mass of one RBC 27–34 pg (normochromic)

Hypochromic RBCs (e.g., iron deficiency)

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 fraction of reticulocytes of all circulating RBCs. Represents erythropoietic activity. 0.5–1.5% Insufficient erythropoiesis (e.g., aplastic anemia) Reactively increased erythropoiesis (e.g., in hemolysis or blood loss)
Corrected reticulocyte count (RI) Absolute reticulocyte count × (patient hematocrit/normal hematocrit ) 1-3%
Reticulocyte production index (RPI)

Absolute reticulocyte count/reticulocyte maturation time × (patient hematocrit/normal hematocrit

In anemia: > 3 normal, < 2 inadequate
Red blood cell distribution width (RDW) Measure of the variation in the size of red blood cells 13%–15% Increased variation in size (called anisocytosis) is a result of conditions that decrease RBC production (e.g. Vitamin B12 deficiency, iron deficiency, sideroblastic anemia).

Erythrocyte morphology and hemoglobin variants

References:[5][6][7][8][8][9][10][11][12][13]

White cell line - leukocytes

Definition Causes
Leukopenia
Leukocytosis
  • > 10,000/μL
Leukemoid reaction
  • leukocyte alkaline phosphatase (LAP) score
  • Typically secondary to infections or drugs (e.g., steroids)
  • Associated with certain solid tumors (e.g., lung and kidney cancer) Mimics a hematopoietic malignancy.

References:[14][15]

White myeloid cell line - granulocytes, mast cells, and monocytes

White myeloid blood cell (leukocyte) production

Granulocytes

Myeloid cell Characteristics Function Increase Decrease
Neutrophil granulocyte (neutrophils)
  • 50–65% of all leukocytes in the blood
  • Diameter: around 12 μm
  • Maturation: Band neutrophils develop into segmented granulocytes over the course of 4–5 days.
  • Migration to the site of inflammation → identification, destruction, and phagocytosis of extracellular infectious agents (bacteria, fungi)
  • Neutropenia (mild: 1000–1500 cells/μL; moderate: 500–1000 cells/μL; severe: < 500 cells/μL → see agranulocytosis):
    • Bone marrow damage
    • Viral infections, e.g., hepatitis
    • On rare occasions in bacterial infection: typhoid fever
    • Kostman syndrome

Eosinophil granulocyte (eosinophils)

  • 1–4% of all leukocytes
  • Eosinophilic (= acidophile) granules → stained pink/red on H&E stain
  • Diameter: around 12 μm
  • Histamine attracts eosinophils to the site of inflammation.

Basophil granulocyte

  • Around 1% of all leukocytes
  • Diameter: around 10 μm
  • Basophilic granules containing histamine and heparin often obscure the nucleus.
  • Surface receptors for IgE
  • Remain in the bloodstream for minutes before migrating into tissue
  • Basopenia

Monocyte

  • Around 3–7% of all leukocytes
  • Diameter: around 5–20 μm
  • Remain in the bloodstream for only around 8 hours before migrating to tissue
  • Monocytosis (> 500/μL or > 7%)

Mast cell

References:[16][17][8][18][19][20][21][22][23][24]

Lymphocytes

Lymphopoiesis (lymphocyte production)

Lymphocyte physiology

  • Concentration: 1000–4000/μL cells
    • Abnormal lymphocyte concentration: See table below.
Definition Causes
Lymphocytosis Increase in number of lymphocytes in the blood to > 4000/μL (absolute) or > 50% (relative)
Lymphocytopenia (lymphopenia) Decrease in number of lymphocytes in the blood to <1000/μL(absolute) or around < 20% (relative)

Lymphocytes are constantly looking for "their" antigen. They account for 20–45% of all leukocytes in the blood!

Natural killer cells (NK cells)

T-lymphocytes (T cells)

Subpopulations Important surface markers Function

Cytotoxic T cells (T-killer cells)

CD8 positive Recognize foreign (mostly viral) antigens presented via MHC-I receptors 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 lymphocytesimmunoglobulin 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

Natural killer T cells (NKT cells)

  • Share characteristics of natural killer (NK) cells and T cells [25]
  • Have T-cell receptors
  • Recognize glycolipids presented via CD1d

B lymphocytes (B cells)

References:[26][15][27][28][29][30][31][32][32]

Agranulocytosis

References:[33][34]

Platelets

Platelet Production

Platelet physiology

  • Function: : forms plug in bleeding vessel (primary hemostasis)
  • Lifespan: circulation for 8–9 days
  • Concentration: 150,000 to 450,000/μL cells
    • Abnormal platelet production: See table below.
Definition Causes
Thrombocytosis Increase in number of platelets in the blood to > 400,000/μL (absolute)
Thrombocytopenia Decrease in number of lymphocytes in the blood to < 150,000/μL (absolute)

References:[35]

Clinical significance

last updated 11/17/2018
{{uncollapseSections(['i4XJQy', 'Nac-ka0', 'NDc-ee0', 'macVOa0', '5aciOa0', 'nac7Oa0', 'MacMOa0', 'lhcvVX0', 'KncU810', 'B9czpe0'])}}