Cell Morphology - Lecture Notes PDF

HEMATOLOGY Introduction PREAMBLE PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY.  PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for detai...

HEMATOLOGY Introduction PREAMBLE PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY.  PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES Unit Objectives are your study guide (not this PowerPoint) Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1 INTRODUCTION Hematology: the study of blood and blood forming tissues. Blood consists of 55% plasma and 45% formed elements. Formed elements include erythrocytes, leukocytes, and thrombocytes. COMPONENTS OF WHOLE BLOOD Figure 17.2 2 ERYTHROCYTES Normal range 4.5-5.9 million per mm3 in adults. Biconcave shape. Diameter 7 microns. Cells for transport of O2 and CO2. Life span 120 days. LEUKOCYTES Normal range 4.4-11.3 thousand per mm3 in adults. Five types. Size 8-20 microns. Involved in fighting infection, combating allergic reactions, and immune responses. Except for lymphocytes white cells life span is approximately 10 days 3  THROMBOCYTES Smallest cells in the blood. Normal range 150,000- 400,000. Active role in coagulation and hemostasis. Cellular Morphology and Foundations of Genetic Hematopoietic Disorders CHAPTER 3 4 CELLULAR STRUCTURE Cellular Membrane  semipermeable separation between the cellular components, the organelles, and the surrounding environment. CELLULAR STRUCTURE Fluid Mosaic Model  Dynamic fluid structure with globular proteins floating in lipids  1. Cell membrane – made up of:  proteins  phospholipids  cholesterol  traces of polysaccharide 5  CELLULAR STRUCTURE 2. Lipids (as phospholipids) are arranged in two layers  polar (charged) phosphate ends are toward inner and outer surfaces with the fatty acid ends toward the interior of membrane  Protein molecules may be incorporated into the lipid bilayer or associated with either the outer or inner surface membranes  Polysaccharides (glycoproteins or glycolipids) are attached to the membrane CELLULAR STRUCTURE Functions  Lipid bilayer – impermeability of membrane  Protein – acts as transport molecule, for the rapid penetration of polar and non-lipid soluble substances. Determines and protects shape and structure of membrane (attached to microtubules and microfilaments)  Carbohydrates (polysaccharides) – surface antigens – functions in recognition of and interaction between cells. 6 MOVEMENT ACROSS CELL MEMBRANE Cytoplasmic membrane maintains cellular integrity of interior of cell by controlling and influencing passage of materials in and out of cell Osmosis – net movement of water molecules through a semipermeable membrane.  Normally water molecules move in and out of cell membrane at an equal rate producing no net movement  If concentration gradient exists, movement of water molecules will be greater from areas of low solute to areas of higher solute concentration.  Basic principle underlying the Erythrocyte Fragility Test – alterations in the erythrocyte membrane can be observed by placing RBC’s in varying concentrations of NaCl. OSMOSIS Osmotic pressure – pressure exerted by water molecules inside membrane at equilibrium In low sodium concentration, the net movement of water is into the cell which will cause the cell to lyse. In high sodium concentration, the net movement of water is out of the cell which will cause cell crenation 7  DIFFUSION Diffusion is an important process in overall cellular physiology, such as the physiological activities of the erythrocyte. This passive process (requires no energy) through a semipermeable membrane may also be referred to as dialysis. Movement of molecules from an area of greater concentration to an area of lesser concentration Diffusion is dependent on: 1. solubility of molecules in liquids 2. Temperature 3. Concentration gradient via hydrophilic regions (where proteins create a pore like opening 4. Calcium ions affect permeability of membranes. ↑ in Ca in fluid around cell or accumulation of Ca in cytoplasm of cell can decrease permeability ACTIVE TRANSPORT Active transport is another essential membrane function.  Particularly important as a metabolic regulator is sodium-potassium-adenosine triphosphatase (Na-K-ATPase).  This enzyme provides the necessary energy to drive the sodium-potassium pump, a fundamental ion transport system.  Sodium ions are pumped out of the cells into extracellular fluids where the concentration of sodium is higher than it is inside the cell.  This movement of molecules is referred to as moving against the concentration gradient and requires energy. The energy-producing activities of the mitochondria are heavily dependent on this process. 8 MOVEMENT ACROSS CELL MEMBRANE Endocytosis is a process of engulfing particles or molecules with formation of membrane-bound vacuoles in the cytoplasm 1) pinocytosis – engulfment of fluids which are discharged into the cytoplasm 2) phagocytosis – engulfment and destruction of particles – the vacuole containing the particle is fused with lysosomes and digestive enzymes are emptied into the vacuole for its destruction. CELL VOLUME HOMEOSTASIS Maintenance of a constant volume despite extracellular and intracellular osmotic challenges is critical to the integrity of a cell. In most cases, cells respond by swelling or shrinking by activating specific metabolic or membrane-transport processes that return cell volume to its normal resting state. These processes are essential for the normal function and survival of cells. 9 REACTIVE AND NEOPLASTIC GROWTH PROCESSES Adaptive cell changes Anaplasia—highly pleomorphic and bizarre cytologic features associated with malignant tumors Atrophy—decrease in the number or size of cells Dysplasia—abnormal cytologic features and tissue organization Hyperplasia—increase in the number of cells in a tissue Hypertrophy—increase in the size of cells Metaplasia—change from one adult cell type to another ORGANELLES OF THE CELL Cytoplasmic Organelles are functional units of a cell that can only be viewed with an electron microscope. Staining with Wrights stain aids in differentiating features of the cells. 10 CYTOPLASMIC ORGANELLES AND METABOLITES #1 Organelles are functional units of a cell.  Cytoplasm  70% to 90% water; Contains proteins, lipids, carbohydrates, minerals, salt and water  Background for all chemical reactions that takes place in the cell  Embedded in cytoplasm are the organelles  Centrioles are two central spots inside of the centrosomes.  Endoplasmic reticulum (ER):  An extensive lace-like network, composed of membranes enclosing interconnecting cavities or cisterns  Classified as either rough (granular) or smooth (agranular)  Rough ER:  Contain ribosomes  Protein production  Smooth ER:  Site of lipid synthesis and fat breakdown for energy usage CYTOPLASMIC ORGANELLES AND METABOLITES #2 Golgi apparatus:  Appears as a horseshoe-shaped or hook-shaped organelle with an associated stack of vesicles or sacs Lysosomes:  Contain hydrolytic enzymes that aid in cellular digestion Microbodies:  Small, intracytoplasmic organelles, limited by a single membrane that is thinner than the lysosome Microfilaments:  Solid structures, consisting of the protein actin and the larger myosin filaments 11 CYTOPLASMIC ORGANELLES AND METABOLITES #3 Microtubules:  Small, hollow fibers composed of polymerized, macromolecular protein subunits, tubulin Mitochondria:  Composed of an outer smooth membrane and an inner folded membrane (cristae)  The cristae contain the enzymes and other molecules that carry out the energy- producing reactions of the cell.  The granules of the matrix function as binding sites for calcium and contain some deoxyribonucleic acid (DNA) and some ribosomes that are similar to those found in microorganisms.  The reaction located on the inner membrane of the mitochondria is enzyme- controlled, energy-producing, and electron transfer-oxidative. CYTOPLASMIC ORGANELLES AND METABOLITES #4 Ribosomes:  Small dense granules.  Lack membranes.  Found both on the surface of the rough ER and free in the cytoplasm.  Contain a significant proportion of ribonucleic acid (RNA) and are composed of unequally sized subunits.  The presence of many ribosomes produces cytoplasmic basophilia (blue color) when a cell is stained with Wright stain.  The complex of messenger RNA (mRNA) and a ribosome serves as the site of protein synthesis. 12 CELLULAR INCLUSIONS AND METABOLITES Glycogen is a long-chain polysaccharide, a storage form of carbohydrate that is detectable with a special cytochemical stain, the periodic acid-Schiff (PAS) stain. Ferritin is a common storage form of iron. It is often found in iron-rich dense bodies referred to as telolysosomes.  The term siderosome is used to refer to iron-saturated telolysosomes.  Histologists refer to granular, iron-rich brown pigment as hemosiderin. NUCLEAR CHARACTERISTICS The nucleus is surrounded by a nuclear envelope, which consists of an inner and an outer membrane. Inside the nucleus, within the inner nucleoplasm, are the  Nucleoli (singular, nucleolus)  Chromatin 13 NUCLEAR ENVELOPE CHROMATIN CHARACTERISTICS #1 To dictate the nature of proteins that can be synthesized, thereby controlling the function of the cell To transmit information for cellular control from one generation to the next 14  CHROMATIN CHARACTERISTICS #2 Proteins associated with the nucleic acids are divided into  Basic, positively charged histones  Believed to be essential to the structural integrity of chromatin  Important in facilitating the conversion of the thin chromatin fibers seen during interphase into the highly condensed chromosomes seen in mitosis  Less positively charged nonhistones  Thought to play other roles, including genetic regulation CHROMATIN CHARACTERISTICS #3 A general model of the organization of DNA and histones depicts a regular spacing arrangement. The complete unit, the nucleosome, consists of a string of DNA wrapped around a histone core. 15 CHROMOSOMES Genetic material that exists as diffuse elongated chromatin fibers prior to mitosis. During cellular division the stands condense into short visible structures Number is constant within each species – humans have 46 chromosomes arranged into 23 pairs, one member of each pair inherited from the father and the other inherited from the mother. 22 pair are autosomes (body chromosomes) and one pair represents the sex chromosomes, either XX or XY. Chromosomes can be grown, harvested, stained, and banded to produce a karyotype CHROMOSOMES 16 CHROMOSOMAL ALTERATIONS Deletion is defined as the loss of a segment of chromosome. Considered a structural aberration. Translocation is the process in which a segment of one chromosome breaks away (is deleted) from its normal location and is usually transposed onto another chromosome (is added). Considered a structural aberration. Trisomy is the failure of a homologous chromosome to separate from its sister chromatid. This leads to a set of three chromosomes in place of the normal pair. Considered a numerical aberration. CHROMOSOME ABNORMALITY Chromosomal Deletion Chromosomal Translocation Trisomy 21 and 13 17 CLINICAL USE OF CYTOGENETICS Clinical cytogenetics contributes to understanding inborn or acquired genetic problems by providing a low-power screening method for detecting isolated or missing chunks of chromosomes. ACTIVITIES OF THE NUCLEUS—INTERPHASE Interphase is where DNA is replicated (or doubled). Interphase is now divided into three subphases:  G1, first gap: 6 to 8 hours; nucleoli become visible, and the chromosomes are extended and metabolically active.  S phase: approximately 6 hours; actual DNA replication, during which growth and metabolic activities are minimal.  G2, second gap: 4 to 5 hours; second period of growth, where DNA can synthesize RNA and proteins to prepare for mitosis. 18 FOUR PHASES OF MITOTIC DIVISION M phase is the period of actual cell division. Prophase is the period of replicated strands of chromatin that become tightly coiled, distinctive structures. Metaphase is the period when identical sister chromatids move to the center of the spindle (the equatorial plate). Anaphase begins as soon as the chromatids are pulled apart and lasts until the newly formed chromosomes reach the opposite poles of the spindle. Telophase is the period when the chromosomes arrive at opposite poles of the cell in early telophase. MITOTIC DIVISION Nuclear division (karyokinesis)  Nucleus divides in half and is followed by cytokinesis. Division of cytoplasm (cytokinesis)  The cytoplasm around the two new nuclei becomes furrowed and the cytoplasmic membrane “pinches” in.  The “pinching” is caused by contraction of a ring of microfilaments. 19 G0 PHASE Characterized as a state of mitotic inactivity. Can be stimulated by hormones during this stage to reenter the mitotic cycle.  This can result in overstimulation and subsequent abnormal proliferation. Other nucleated cells, such as nerve cells, lose their ability to undergo mitosis and remain in G0 permanently. APOPTOSIS Apoptosis is a means of distinguishing a morphologically distinctive form of programmed cell death that is associated with normal physiology. Apoptosis versus necrosis:  Necrosis is “passive” cell death, with no known regulatory mechanisms.  Apoptosis is “active” cell death, with known molecular mechanisms. 20 APOPTOSIS VERSUS NECROSIS DISORDERS OF DECREASED OR INCREASED APOPTOSIS Decreased apoptosis:  Leukemia  Systemic lupus erythematosus (SLE)  Follicular lymphoma  Cancers with p53 mutations Increased apoptosis:  Acquired immunodeficiency syndrome (AIDS)  Aplastic anemia  Myelodysplastic syndromes (MDS) 21 MEIOSIS FOUNDATIONS OF GENETIC INTERACTIONS A gene is a segment of DNA that is arranged along the chromosome at a specific position called a locus. Each gene has a unique sequence of nucleotides that is transcribed into mRNA. In most cases, the coding sequences, or exons, are interrupted by intervening noncoding sequences, or introns. 22 GENETIC ALTERATIONS A change in the gene is caused by mutation producing a change in the actual structure of DNA. SICKLE CELL MUTATION #1 23 SICKLE CELL MUTATION #2 SICKLE CELL MUTATION #3 24 ONCOGENES Cancer including leukemias and lymphomas is caused by alteration in oncogenes, tumor-suppressor genes, and microRNA genes. A multistep process of sequential alteration in several, often many, oncogenes, tumor-suppressor genes, or microRNA genes in the affected cells. PROTOONCOGENES Many viral oncogenes have normal counterparts in the human genome, called protooncogenes. Protooncogene activity in normal growth include:  Growth factors  Growth factor receptors  Signal transducers  Transcription factors 25 CANCER STEM CELLS When a normal hematopoietic precursor cell, a stem cell, or more differentiated progenitor cell acquires a cancer-inducing mutation, it is called a hematopoietic neoplasm or cancer-initiating cell. A cancer-initiating cell produces a cancer stem cell. Most malignancies arise from diverse abnormal cell populations. The hematopoietic equivalent of the cancer stem cell is the leukemic stem cell. TUMOR PROTEIN, P53 p53 gene is important in regulation of the cell cycle and functions as a tumor suppressor. p53 can activate the repair of DNA when damaged, can hold the cell cycle at the G1/S regulation point until DNA can be repaired and continue in the cell cycle, and can initiate apoptosis if DNA damage is beyond repair. Mutations in p53 cause disruption of the housekeeping of damaged cells thereby leading to uncontrolled cell proliferation or cancer. 26 POSTAMBLE READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 27