Hematopoietic Dysfunction PDF

CHAPTER 13 Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System Box 13.1 815  Mechanisms of Disease in Bone Marrow and Blood Cells BONE MARROW Hypoplasia Hyperplasia Dysplasia Aplasia Neoplasia Myelophthisis (fibrosis, metastatic neoplasia) Necrosis Inflammation BLOOD CELLS Figure 13.6 Megak...

CHAPTER 13 Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System Box 13.1 815  Mechanisms of Disease in Bone Marrow and Blood Cells BONE MARROW Hypoplasia Hyperplasia Dysplasia Aplasia Neoplasia Myelophthisis (fibrosis, metastatic neoplasia) Necrosis Inflammation BLOOD CELLS Figure 13.6 Megakaryocyte, Canine Bone Marrow Aspirate. Note the cell’s very large size, lobulated nucleus, and abundant granular cytoplasm. Wright’s stain. (Courtesy Dr. M.M. Fry, College of Veterinary Medicine, University of Tennessee.) adult animals are primarily dependent upon extramedullary lymphocyte production and kinetics, and not lymphopoiesis by the marrow. In healthy nonruminant mammals, lymphocytes are the second most numerous blood leukocyte. According to conventional wisdom, cattle normally have higher numbers of lymphocytes than neutrophils in circulation. However, recent studies suggest that is no longer the case, most likely because of changes in genetics and husbandry. In most species, the majority of lymphocytes in blood circulation are T lymphocytes. The concentration of blood lymphocytes decreases with age. Increased destruction Hemorrhage (especially erythrocytes) Consumption (platelets) Neoplasia Altered distribution Abnormal function binding sites for the extrinsic tenase (factors III, VII, and X), intrinsic tenase (factors IX, VIII, and X), and prothrombinase (factors X, V, and II) coagulation complexes. Platelet glycoprotein surface receptors include those for binding vWF (GPIb-IX-V), collagen (GPVI), and fibrinogen (GPIIb-IIIa), which facilitate platelet aggregation and adherence to subendothelial collagen. Expansion of surface area and release of granule contents are aided by a network of membrane invaginations known as the open canalicular system. This system is not present in horses, cattle, and camelids. Methods for Examination of the Bone Marrow Gross and Microscopic Examination Thrombopoiesis. Thrombopoiesis—from thrombos (Gr., clot)— refers to the production of platelets, which are small (2 to 4 μm), round to ovoid, anucleate cells within blood vessels. Platelets have a central role in primary hemostasis but also participate in secondary hemostasis (coagulation) and inflammatory pathways (see Chapter 2, Vascular Disorders and Thrombosis, and Chapter 3, Inflammation and Healing). Thrombopoietin (Tpo) is the primary regulator of thrombopoiesis. The liver and renal tubular epithelial cells constantly produce Tpo, which is then cleared and destroyed by platelets and their precursors. Therefore, plasma Tpo concentration is inversely proportional to platelet and platelet precursor mass. If the platelet mass is decreased, less Tpo is cleared, and there is subsequently more free plasma Tpo to stimulate thrombopoiesis. The earliest morphologically identifiable platelet precursor is the megakaryoblast, which undergoes nuclear reduplications without cell division, termed endomitosis, to form a megakaryocyte with 8 to 64 nuclei. As the name suggests, megakaryocytes are very large cells, much larger than any other hematopoietic cell (Fig. 13.6; also see Fig. 13.1). Megakaryocytes neighbor venous sinusoids, extend their cytoplasmic processes into vascular lumens, and shed membrane-bound cytoplasmic fragments (platelets) into blood circulation. Orderly platelet shedding is partially facilitated by β1-tubulin microtubules within megakaryocytes. Platelets circulate in a quiescent form and become activated by binding platelet agonists, including thrombin, adenosine diphosphate (ADP), and thromboxane. Platelet activation causes shape change, granule release, and relocation of procoagulant phospholipids and glycoproteins to the outer cell membrane. Specific procoagulant actions include release of calcium, von Willebrand factor (vWF), factor V, and fibrinogen, as well as providing phosphatidylserine-rich Information on this topic is available at www.expertconsult.com. Complete Blood Count Information on this topic is available at www.expertconsult.com. Additional Tests Information on biopsies, direct antiglobulin test, flow cytometry, immunophenotyping, and polymerase chain reaction (PCR) is available at www.expertconsult.com. Hemostasis Testing Information on this topic is available at www.expertconsult.com. Dysfunction/Responses to Injury Bone Marrow Mechanisms of bone marrow disease are summarized in Box 13.1. Hematopoietic cells’ response to injury is dependent upon whether the insult is on the marrow or within extramarrow tissues. In general, marrow-directed injury or disturbances result in production of abnormal hematopoietic cells (dysplasia), fewer hematopoietic cells (hypoplasia),c or a failure of hematopoietic cell development (aplasia). Dysplasia, hypoplasia, and aplasia may be specific for one cThe term “hypoplasia” is used differently with regard to the bone marrow versus nonmarrow sites. Outside of the marrow, hypoplasia is used to indicate that a tissue or organ failed to initially develop. Marrow hypoplasia indicates that hematopoietic cells decreased production after normal development. This would be termed “atrophy” in nonmarrow sites. CHAPTER 13 Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System Bone marrow is not routinely sampled during postmortem examinations. However, indications for bone marrow evaluation include suspected leukemia, metastatic neoplasia within bone marrow, or infectious myelitis, as well as cytopenia(s) or hematopoietic dysplasia of unknown cause. Multimodal evaluation is ideal, including a recent (