Elaine M. Keohane*
6
OUTLINE Cell Organization Plasma Membrane
Membrane Proteins Membrane Carbohydrates Nucleus
Chromatin Nuclear Envelope Nucleoli Cytoplasm
Ribosomes
Endoplasmic Reticulum Golgi Apparatus Mitochondria Lysosomes
Microfilaments and Interme-diate Filaments
Microtubules Centrosomes
Hematopoietic Microenvi-ronment
Cell Cycle
Regulation of the Cell Cycle Cell Death by Necrosis and
Apoptosis
*The author extends appreciation to Keila B. Poulsen, whose work in prior editions provided the foundation for this chapter.
OBJECTIVES
After completion of this chapter, the reader will be able to:
1. Describe the structure, composition, and general function of cellular membranes.
2. Describe the structure, composition, and function of components of the nucleus, including staining quali-ties visible by light microscopy.
3. Describe the structure, composition, and general function of the cytoplasmic organelles in the cell, in-cluding staining qualities visible by light microscopy, if applicable.
4. Describe the general structure and function of the hematopoietic microenvironment.
5. Associate the stages of the cell cycle with activities of the cell.
6. Describe the role of cyclins and cyclin-dependent ki-nases in cell cycle regulation.
7. Discuss the function of checkpoints in the cell cycle and where in the cycle they occur.
8. Differentiate between apoptosis and necrosis.
K
nowledge of the normal structure, composition, and function of cells is fundamental to the understanding of blood cell pathophysiology covered in later chapters.From the invention of the microscope and the discovery of cells in the 1600s to the present-day highly sophisticated analysis of cell ultrastructure with electron microscopy and other technolo-gies, a remarkable body of knowledge is available about the structure of cells and their varied organelles. Complementing these discoveries were other advances in technology that enabled detailed understanding of the biochemistry, metabo-lism, and genetics of cells at the molecular level. Today, highly sophisticated analysis of cells using flow cytometry, cytogenet-ics, and molecular genetic testing (Chapters 30, 31, and 32) has become the standard of care in diagnosis and management of many malignant and non-malignant blood cell diseases.
This new and ever-expanding knowledge has revolutionized the
diagnosis and treatment of hematologic diseases resulting in a dramatic improvement in patient survival for many conditions that previously had a dismal prognosis. With all these advances, however, the visual examination of blood cells on a peripheral blood film by light microscopy still remains the hallmark for the initial evaluation of hematologic abnormalities.
This chapter will provide an overview of the structure, com-position, and function of the components of the cell, the he-matopoietic microenvironment, the cell cycle and its regula-tion, and the process of cell death by apoptosis and necrosis.
CELL ORGANIZATION
Cells are the structural units that constitute living organisms (Figures 6-1 and 6-2). Cells have specialized functions and con-tain the components necessary to perform and perpetuate these
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PART II Blood Cell Production, Structure, and Function• Other unique subcellular structures and organelles that sup-port the various cellular functions.1
Table 6-1 summarizes the cellular components and their functions, which are explained in more detail later.
PLASMA MEMBRANE
The plasma membrane serves as a semipermeable outer bound-ary separating the cellular components from their surrounding environment. The cell membrane serves four basic functions:
(1) it provides a physical but flexible barrier to contain and protect cell components from the extracellular environment;
(2) it regulates and facilitates the interchange of substances with the environment by endocytosis, exocytosis, and selective permeability (using various membrane channels and trans-porters); (3) it establishes electrochemical gradients between the interior and exterior of the cell; and (4) it has receptors that allow the cell to respond to a multitude of signaling molecules through signal transduction pathways.2
Relevant to hematology, the membrane is also the location of cell surface glycoprotein and glycolipid molecules (surface markers or antigens) used for blood cell identity. Each type of blood cell expresses a unique repertoire of surface markers at different stages of differentiation.3 Monoclonal antibodies are used to identify a blood cell’s surface antigens using flow cytom-etry (Chapter 32). An international nomenclature was devel-oped, called the cluster of differentiation, or CD, system, in which a CD number was assigned to each identified blood cell surface antigen.4 Over 350 CD antigens have been identified on blood Nuclear pore
Rough endoplasmic reticulum Perinucleolar chromatin
Euchromatin Heterochromatin
Free ribosomes Smooth endoplasmic reticulum Nucleolus Nuclear envelope Chromatin
Microfilaments Glycogen aggregates
Golgi complex
Vacuole Mitochondria
Lysosome Microtubule Centriole
Figure 6-1 Cell organization and components.
Nuclear pore
Golgi body
Nucleolus Nucleus
Lysosomes
Mitochondria Rough endoplastic reticulum Figure 6-2 Electron micrograph of a cell. (From Carr JH, Rodak BF:
Clinical hematology atlas, ed 4, St. Louis, 2013, Saunders.)
functions. Regardless of shape, size, or function, human cells contain:
• A plasma membrane that separates the cytoplasm and cellular components from the extracellular environment;
• A membrane-bound nucleus (with the exception of mature red blood cells and platelets); and
CHAPTER 6 Cellular Structure and Function
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cells.3 The CD nomenclature allows scientists, clinicians, and laboratory practitioners to communicate in a universal language for hematology research and diagnostic and therapeutic practice.
In addition to the plasma membrane, many components found within the cell (e.g., the mitochondria, Golgi apparatus, nucleus, and endoplasmic reticulum) have similarly con-structed membrane systems. The red blood cell membrane has been the most widely studied and serves as an example of a cell membrane (Figure 9-2).
To accomplish its many requirements, the cell mem-brane must be resilient and elastic. It achieves these qualities by being a fluid structure of proteins floating in lipids. The lipids are phospholipids and cholesterol arranged in two layers. The phosphate end of the phospholipid and the hydroxyl radical of cholesterol are polar-charged hydro-philic (water-soluble) structures that orient toward the ex-tracellular and cytoplasmic surfaces of the cell membrane.
The fatty acid chains of the phospholipids and the steroid
Organelle Location Appearance and Size Function
Plasma membrane Outer boundary of cell Lipid bilayer consisting of phospholipids, cholesterol, proteins; glycolipids and glycoproteins form a glycocalyx
Provides physical barrier for cell; facili-tates and restricts cellular exchange of substances; maintains electro-chemical gradient and receptors for signal transduction
Nucleus Within cell Round or oval; varies in diameter;
composed of DNA and proteins
Controls cell division and functions; and contains genetic code
Nucleolus Within nucleus Usually round or irregular in shape;
2-4 mm in diameter; composed of ribosomal RNA and the genes coding it, and accessory proteins;
there may be one to several within the nucleus
Synthesizes ribosomal RNA and assem-bles ribosome subunits
Ribosomes Free in cytoplasm; also on outer surface of rough endoplasmic reticulum
Macromolecular complex composed of protein and ribosomal RNA; com-posed of large and small subunits
Synthesizes proteins
Rough endoplasmic reticulum
Membranous network throughout cytoplasm
Membrane-lined tubules that branch and connect to nuclear membrane;
studded with ribosomes
Synthesizes most membrane-bound proteins
Smooth endoplasmic reticulum
Membranous network throughout cytoplasm
Membrane-lined tubules contiguous with rough endoplasmic reticulum;
does not have ribosomes
Synthesizes phospholipids and steroids;
detoxifies drugs; stores calcium
Golgi apparatus Next to nucleus and rough endoplasmic reticulum
System of stacked, membrane-bound, flattened sacs
Modifies and packages macromolecules for other organelles and for secretion Mitochondria Randomly distributed in cytoplasm Round or oval structures; 3-14 nm in
length, 2-10 nm in width;
membrane has two layers; inner layer has folds called cristae
Produces most of the cell’s ATP by oxidative phosphorylation
Lysosomes Randomly distributed in cytoplasm Membrane-bound sacs; diameter varies
Contains hydrolytic enzymes that degrade unwanted material in the cell Microfilaments Near nuclear envelope, plasma
membrane, and mitotic processes
Double-stranded, intertwined solid structures of actin; 5-7 nm in diameter
Supports cytoskeleton and motility
Intermediate filaments Cytoskeleton Solid structures 8-10 nm in diameter;
self-assemble into larger bundles
Provides strong structural support
Microtubules Cytoskeleton and centrioles, near nuclear envelope and Golgi apparatus
Hollow cylinder of a- and b-tubulin forming 13 protofilaments; 20-25 nm in diameter
Maintains cell shape, motility, and mitotic process
Centrosome Near nucleus Composed of two centrioles, each
having nine sets of triplet microtubules; 150 nm in diameter, 300-500 nm in length
Contains centrioles that serve as insertion points for mitotic spindle fibers
TABLE 6-1 Summary of Cellular Components and Functions