Blood PDF

C H A P T E R 18 BLOOD Emile L. Boulpaep Blood is a complex fluid consisting of plasma—extracellular fluid on account of the volume occupied by proteins and fluid rich in proteins—and of formed elements—red blood their electrical charge (see Table 5-2). cells (RBCs), white blood ce...

C H A P T E R 18 BLOOD Emile L. Boulpaep Blood is a complex fluid consisting of plasma—extracellular fluid on account of the volume occupied by proteins and fluid rich in proteins—and of formed elements—red blood their electrical charge (see Table 5-2). cells (RBCs), white blood cells (WBCs), and platelets. Total Plasma proteins at a normal concentration of ~7.0 g/dL blood volume is ~70 mL/kg body weight in the adult woman account for a colloid osmotic pressure or oncotic pressure and ~80 mL/kg body weight in the adult man (see Table 5-1). of ~25 mm Hg (see p. 470). Principal plasma proteins are albumin, fibrinogen, globulins, and other coagulation factors. The molecular weights of plasma proteins range BLOOD COMPOSITION up to 970 kDa (Table 18-1). The plasma concentration of albumin ranges from 3.5 to 5.5 g/dL, which provides the Whole blood is a suspension of cellular body with a total plasma albumin pool of ~135 g. Albumin elements in plasma is synthesized by the liver at a rate of ~120 mg/kg body If you spin down a sample of blood containing an anticoagu- weight per day and, due to catabolism, has a half-life in the lant for ~5 minutes at 10,000 g, the bottom fraction contains circulation of ~20 days. Urinary losses of albumin are nor- formed elements—RBCs (or erythrocytes), WBCs (leuko- mally negligible (40 mm thick in certain inflammatory disorders). This rate of fall is called the erythrocyte sedimentation rate (ESR). Although it is nonspecific because so many different conditions can cause it to increase, the ESR is still widely used mobility (Fig. 18-2A): albumin, α1-globulins, α2-globulins, by clinicians to assess the presence and severity of inflamma- β-globulins, fibrinogen, and γ-globulins. The three most tion. It is a simple technique, easily performed in a physician’s abundant peaks are albumin, fibrinogen, and γ-globulins. office. As an example of its utility, a patient with an inflamma- The γ-globulins include the immunoglobulins or antibodies, tory process that naturally waxes and wanes, such as lupus erythematosus, may present with nonspecific complaints which can be separated into IgA, IgD, IgE, IgG, and IgM. such as fatigue, weakness, and achiness. An elevated ESR Immunoglobulins are synthesized by B lymphocytes and would suggest that these complaints are due to the reactiva- plasma cells. tion of the disease and not just to a poor night’s sleep or Clinical laboratories most often perform electrophoresis depression. of blood proteins on serum instead of plasma (see Fig. 18-2B). Table 18-1 shows the major protein components  Chapter 18 Blood 431 A PLASMA PROTEINS Bone marrow is the source of most blood cells Alb 1 2 12  If you spread a drop of anticoagulated blood thinly on a glass slide, you can detect under the microscope the cellular ele- ments of blood. In such a peripheral blood smear, the fol- lowing mature cell types are easily recognized: erythrocytes; granulocytes divided in neutrophils, eosinophils, and baso- Gc Hpt AT3 Pl CRP phils; lymphocytes; monocytes; and platelets (Fig. 18-3). -Lp C1q Hematopoiesis is the process of generation of all the cell 1Ac types present in blood. Because of the diversity of cell types generated, hematopoiesis serves multiple roles ranging from 1At Tf 2M C3 Fibr the carriage of gases to immune responses and hemostasis. C4 IaTl C5 Pluripotent long-term hematopoietic stem cells (LT-HSCs) Pre A 1Ag -LP IgM constitute a population of adult stem cells found in bone C1Inh Hpx marrow that are multipotent and able to self-renew. The C1s IgA IgD(E) short-term hematopoietic stem cells (ST-HSCs) give rise Cer to committed stem cells or progenitors, which after prolif- eration are able to differentiate into lineages that in turn give Alb IgG rise to burst-forming units (BFUs) or colony-forming units C1r FB Fibrinogen (CFUs), each of which ultimately will produce one or a limited number of mature cell types: erythrocytes, the mega- B SERUM PROTEINS karyocytes that give rise to platelets, eosinophils, basophils, Alb 1 2 12  neutrophils, monocytes-macrophages/dendritic cells, and B or T lymphocytes and natural killer cells (Fig. 18-4). Soluble factors known as cytokines guide the development of each lineage. The research of Donald Metcalf demonstrated the importance of a family of hematopoietic cytokines that stim- ulate colony formation by progenitor cells, the colony- Gc AT3 Pl CRP stimulating factors. The main colony-stimulating factors Hpt -Lp C1q are granulocyte-macrophage colony-stimulating factor 1Ac (GM-CSF; see p. 70), granulocyte colony-stimulating factor Notice absence (G-CSF), macrophage colony-stimulating factor (M-CSF), 1At 2M Tf C3 interleukin-3 (IL-3) and IL-5 (see p. 70), thrombopoietin C4 of fibrinogen. IaTl C5 (TPO), and erythropoietin (EPO; see pp. 431–433). Pre A 1Ag -LP IgM GM-CSF is a glycoprotein that stimulates proliferation of C1Inh Hpx a common myeloid progenitor and promotes the production C1s IgA IgD(E) of neutrophils, eosinophils, and monocytes-macrophages. Cer Recombinant GM-CSF (sargramostim [Leukine]) is used Alb IgG clinically after bone marrow transplantation and in certain C1r FB acute leukemias. G-CSF and M-CSF are glycoproteins that guide the ultimate development of granulocytes and monocytes- Figure 18-2 Electrophoretic pattern of human plasma and serum pro- teins. Normal concentration ranges are as follows: total protein, 6 to macrophages/dendritic cells, respectively. Recombinant G- 8 g/dL; albumin, 3.1 to 5.4 g/dL; α1-globulins, 0.1 to 0.4 g/dL; α2-globulins, CSF (filgrastim [Neupogen]) is used therapeutically in 0.4 to 1.1 g/dL; β-globulins, 0.5 to 1.2 g/dL; γ-globulins, 0.7 to 1.7 g/dL. neutropenia (e.g., after chemotherapy). M-CSF is also re- quired for osteoclast development (see p. 1057 and Fig. 52-4). IL-3 (also known as multi-CSF) has a broad effect on multiple lineages. The liver and the kidney constitutively that are readily resolved by electrophoresis. Proteins present produce this glycoprotein. IL-5 (colony-stimulating factor, in plasma at low concentrations are identified by immuno- eosinophil), a homodimeric glycoprotein, sustains the termi- logical techniques, such as radioimmunoassay (see p. 976) nal differentiation of eosinophilic precursors. or enzyme-linked immunosorbent assay. Not listed in TPO binds to a TPO receptor called c-Mpl, which is Table 18-1 are several important carrier proteins present the cellular homolog of the viral oncogene v-mpl (murine in plasma: ceruloplasmin (see p. 970), transcobalamin (see myeloproliferative leukemia virus). On stimulation by TPO, p. 937), corticosteroid-binding globulin (CBG; see p. 1021), the Mpl receptor induces an increase in the number and insulin-like growth factor (IGF)–binding proteins (see size of megakaryocytes—the cells that produce platelets— p. 996), sex hormone–binding globulin (SHBG or TeBG; see which thereby greatly augments the number of circulating pp. 1119–1120), thyroid-binding globulin (see pp. 1008– platelets. 1009), and vitamin D–binding protein (see p. 1064). The EPO, N18-2 which is homologous to TPO, is pro- liver synthesizes most of the globulins and coagulation duced by the kidney and to a lesser extent by the liver. This factors. N18-1 cytokine supports erythropoiesis or red cell development  Chapter 18 Blood 431.e1 N18-1 Plasma Proteins Contributed by Emile Boulpaep Protein Conventional Units International Units Protein, total 6.4–8.3 g/dL 64.0–83.0 g/L Electrophoresis Albumin: 3.5–5.0 g/dL 35–50 g/L α1-globulin: 0.1–0.3 g/dL 1–3 g/L α2-globulin: 0.6–1.0 g/dL 6–10 g/L β-globulin: 0.7–1.1 g/dL 7–11 g/L γ-globulin: 0.8–1.6 g/dL 8–16 g/L Acid phosphatase M: 2.5–11.7 U/L F: 0.3–9.2 U/L Alanine aminotransferase (ALT, SGPT) M: 10–40 U/L 0.17–0.68 µkat/L F: 7–35 U/L 0.12–0.60 µkat/L Albumin 3.4–4.8 g/dL 34–48 g/L Alkaline phosphatase 25–100 U/L Adult (>20 yr) 0.43–1.70 µkat/L Amylase 27–131 U/L 0.46–2.23 µkat/L Angiotensin I