Introduction To Pathology - Cell Death (PDF)

INTRODUCTION TO PATHOLOGY  PATHOLOGY Pathology – study of disease; describes the effects, progress and consequences of disease and attempt to determine the cause and underlying mechanisms. 2 main division: Anatomic Pathology Clinical Pathology  PATHOLOGY: DIVISION...

INTRODUCTION TO PATHOLOGY  PATHOLOGY Pathology – study of disease; describes the effects, progress and consequences of disease and attempt to determine the cause and underlying mechanisms. 2 main division: Anatomic Pathology Clinical Pathology  PATHOLOGY: DIVISION Anatomic Pathology – primarily consists of tissue evaluation from: individual cells from a pap smear, fine needle aspiration of a mass, or evaluation of the entire body in an autopsy, and everything in between. Surgical Cytopathology Forensic  PATHOLOGY: DIVISION Clinical Pathology – clinical pathology covers most of the laboratory medicine: routine tests such as glucose and sodium, molecular tests for cancer markers, and genome sequencing Includes numerous areas: BB, Microbio, Hema, Chem, Molebio  FIELD OF PATHOLOGY Devoted to understanding the causes of disease and the changes in cells, tissues, and organs that are associated with disease and give rise to the presenting signs and symptoms  FIELD OF PATHOLOGY Etiology – underlying causes and modifying factors responsible for initiation and progression of disease Pathogenesis – mechanism of development and progression of disease  CAUSES OF DISEASE Environmental Factors Genetic Factors  CAUSES OF DISEASE: ENVIRONMENTAL FACTOR Physical agents – Trauma, radiation, both ionizing and non-ionizing, extremes of temperature and electrical power. Chemical poisons – Toxic to all tissues Infections and Infestations – Viruses, bacteria, fungi, protozoa Nutritional deficiencies and excesses – Inadequate supply, inefficient transport within the body, dietary excess Abnormal immune reactions – Normally protective immune system become deranged and damage individual  CAUSES OF DISEASE: ENVIRONMENTAL FACTOR Hypoxia and Ischemia – common causes of cell injury Hypoxia – oxygen deficiency Ischemia – reduced blood supply The most common cause of hypoxia is ischemia resulting from an arterial obstruction  CAUSES OF DISEASE: GENETIC FACTOR Normal genes – genetic polymorphism strongly influence SUSCEPTIBILITY and RESISTANCE to disease Susceptibility of fair skin to damage by UV light (skin cancer) Individual’s HLA type strongly influence Abnormal genes – mutations which give rise to disease (affect single base pair, chromosomal translocation, extra chromosome)  OVERVIEW OF CELLULAR RESPONSES TO STRESS AND NOXIOUS STIMULI Cells actively interact with their environment, constantly adjusting their structure and function to accommodate changing demands and extracellular stresses. The intracellular milieu of cells is normally tightly regulated, state referred to as homeostasis.  OVERVIEW OF CELLULAR RESPONSES TO STRESS AND NOXIOUS STIMULI As cells encounter physiologic stresses or potentially injurious conditions, cells undergo adaptation Cell injury – if the adaptive capability exceeded or stress is inherently harmful Reversible – cell can return to stable baseline Irreversible – death of affected cells  CELL DEATH Necrosis – morphological manifestation of accidental cell death Apoptosis – morphologic appearance of most types of regulated cell death Necroptosis – regulated cell death shows feature of both necrosis and apoptosis  CELL DEATH: NECROSIS Rapid and uncontrollable form of death Inevitable end result of severe damage that is beyond salvage Happens accidentally; injury is too severe to be repaired by many cellular constituents Cellular membrane fall apart, cellular enzymes leak out Elicit a local host reaction called inflammation  CELL DEATH: MORPHOLOGIC CHANGES OF CELLS IN NECROSIS Cytoplasmic changes – increased eosinophilia (increased binding to eosin) – glassy, homogeneous appearance (loss of glycogen particles) – when enzyme digested cytoplasmic organelles becomes vacuolated “moth-eaten”  CELL DEATH: MORPHOLOGIC CHANGES OF CELLS IN NECROSIS Nuclear changes – assume one of the 3 patterns breakdown of DNA and chromatin Pyknosis – nuclear shrinkage and become dense Karyorrhexis – fragmentation of pyknotic nucleus Karyolysis – nucleus fades and dissolves  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Coagulative necrosis Form of necrosis which the underlying tissue architecture is preserved for at least several days after death of cells in the tissue Affected tissue take on a firm texture Characteristic of infarcts (cell death caused by ischemia) in all solid organs except the brain Hallmark appearance: “tombstone” Ex: MI  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Liquefactive necrosis Seen in focal bacterial and occasionally fungal infx because microbes stimulate rapid accumulation of inflammatory cells, and enzymes of leukocytes digest “liuefy” the tissue Obscure reason, hypoxic death of cells within the CNS often evokes liquefactive necrosis Complete destruction of cells/ Dead cells are completely digested Ex: Cerebral infarct  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Gangrenous necrosis Not a distinctive pattern of cell death but still commonly used Condition of a limb that has lost its blood supply and has undergone coagulative necrosis Bacterial infx is superimposed 3 types Dry gangrene Wet gangrene Gas gangrene  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Dry Gangrene – occurs in the toes and feet of elderly people/ diabetics suffering from gradual arterial occlusion. Ex: Distal limbs Wet Gangrene – tissues are moist at the start of the process due to venous congestion/ occlusion or edema. Ex: Bacterial Infx Gas Gangrene – caused by exotoxin-producing bacteria  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Caseous necrosis Most often encountered in foci of tuberculous infx Caseous means “cheeselike” referring to the friable yellow-white appearance of the area of necrosis on gross examination Cheesy and white appearance Tissue architecture is completely obliterated and cellular outlines cannot be discerned Microscopically appears as an amorphous eosinophilic appearance  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Fat necrosis Refers to focal areas of fat destruction, resulting from the release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity Chalky white appearance Ex: Pancreatitis  CELL DEATH: PATTERN OF GROSS APPEARANCE IN NECROTIZED ORGAN/ CELLS Fibrinoid necrosis Special form of necrosis Usually occurs in immune rxn in which complexes of Ags and Abs are deposited in the walls of blood vessels, but may also occur in severe hypertension.  CELL DEATH: APOPTOSIS Activate precise set of molecular pathways that culminate in death “Regulated” cell death Eliminates cells with a variety of intrinsic abnormalities and promotes clearance of the fragments of dead cells WITHOUT eliciting inflammation. (cleared with little leakage)  CELL DEATH: APOPTOSIS Physiologic apoptosis – during normal development of an organism, some cells die and are replaced by new ones – Unwanted cells are eliminated without eliciting potentially harmful inflammation. Pathologic apoptosis – eliminates cells that are damaged beyond repair. Seen in DNA damage CELL DEATH: CAUSES OF APOPTOSIS CELL DEATH: MECHANISM OF APOPTOSIS CELL DEATH: NECROSIS VS APOPTOSIS  SOMATIC DEATH Death of an organism as a WHOLE Primary Changes Secondary Changes  SOMATIC DEATH: PRIMARY CHANGES Circulatory Failure Respiratory Failure CNS Failure SOMATIC DEATH: SECONDARY CHANGES Algor Mortis – first demonstrable change (cooling of body) Rigor Mortis – stiffening of the body Livor Mortis – purplish discoloration or lividity of skin Putrefaction – rotting or decomposition of body by bacterial action Greenish blue discoloration, Muscle softening/ loss of rigor mortis, Skin peeling Autolysis – liberation of hydrolytic enzymes (self-digestion of cells) Postmortem Clotting – settling and separation of RBC from the fluid phase Dessication – drying and wrinkling of the cornea and anterior chamber