Pathology...pptx

Pathology...pptx

• 1.
  **Course title: Pathology.(i.e. Greek pathos = suffering, and logy = study)…. so, What is pathology? •Pathology is the study of the causes and effects of disease or injury. *As applied to modern medicine, it is the study of disease, as the disease originates at the cellular level, whereas, the cellular disturbances arise from alterations in molecules (genes, proteins, and others) that influence the survival and behavior of cells. Therefore, the foundation of modern pathology is understanding the cellular and molecular abnormalities that give rise to diseases.
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  **Four aspects ofa disease process that form the core of pathology: Its cause (etiology) Mechanisms of its development (pathogenesis) Structural alterations induced in cells & organs (morphological changes) Functional consequences of the morphologic changes (clinical significance)
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  Chapt 1: CellInjury, Cell Death, and Adaptation INTRODUCTION: The field of pathology is devoted [consigned] to understanding the causes of disease and the changes in cells, tissues, and organs that are associated with disease. There are two important terms that will encounter throughout the study of pathology and medicine: • Etiology refers to the underlying causes and modifying factors that are responsible for the initiation and progression of disease. It is now clear that many common diseases, such as hypertension, diabetes, and cancer, are caused by a combination of inherited genetic susceptibility (weakness) and various environmental triggers. Clarifying the genetic and environmental factors underlying diseases is a major subject of modern medicine. • Pathogenesis refers to the mechanisms of development and progression of disease, which account for the cellular and molecular changes that give rise to the specific functional and structural abnormalities that characterize any particular disease.
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  • Thus, etiologyrefers to why a disease arises and pathogenesis describes how a disease develops ****(as fig: shows)*** **fig: Steps in the evolution of disease. Only selected major causes (etiologies) are shown.
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  Thereby; in thischapter we discuss “first the causes, mechanisms, and consequences of the various forms of acute cell injury, including reversible injury and cell death. And then being consider cellular adaptations to stress and conclude with two other processes that affect cells and tissues: *the deposition of abnormal substances and *cell aging. 1.1- CAUSES OF CELL INJURY. *Genetic aberrations can result in pathologic changes as congenital malformations associated with Down syndrome or as the single amino acid substitution in hemoglobin, giving rise to sickle cell anemia… • Genetic defects may cause deficiency of functional proteins, such as enzymes or accumulation of damaged DNA or mis- folded proteins, both of which trigger cell death when they are beyond repair..
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  (deprivation = Deficiency) Themost common cause of hypoxia is ischemia resulting from an arterial obstruction, but oxygen deficiency also can result from inadequate oxygenation of the blood, as in a variety of diseases affecting the lung, or from reduction in the oxygen-carrying capacity of the blood, as with anemia of any cause, and carbon monoxide (CO) poisoning. [Impeded = Obstructed]
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  **Toxins. Potentially toxicagents are encountered daily in the environment; these include air pollutants, insecticides, CO, asbestos, cigarette smoke, ethanol, and drugs. Many drugs in therapeutic doses can cause cell or tissue injury in a vulnerable patient or in many individuals if used excessively or inappropriately. **NB: Even innocuous[harmless] substances, such as glucose, salt, water and oxygen, can be toxic….
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  • Infectious agents.All types of disease-causing pathogens, including viruses, bacteria, fungi, and protozoans, injure cells.
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  • Immunologic reactions.Although the immune system defends the body against pathogenic microbes, immune reactions also can result in cell and tissue injury. Examples are autoimmune reactions against one’s own tissues, allergic reactions against environmental substances. In all of these situations, immune responses cause inflammatory reactions, which are often the cause of damage to cells and tissues..
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  • Nutritional imbalances.Protein–calorie insufficiency among impoverished populations remains a major cause of cell injury, and specific vitamin deficiencies are not uncommon even in developed countries with high standards of living (Chapter 8). Ironically, excessive dietary intake may result in obesity and also is an important underlying factor in many diseases, such as type 2 diabetes mellitus and atherosclerosis. • Physical agents. Trauma, extremes of temperature, radiation, electric shock, and sudden changes in atmospheric pressure all have wide- ranging effects on cells (Chapter 8). • Aging. Cellular senescence results in a diminished ability of cells to respond to stress and, eventually, the death of cells and of the organism…
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  Reversible Cell Injury Reversibleinjury is the stage of cell injury at which the deranged function and morphology of the injured cells can return to normal if the damaging stimulus is removed (Fig. shows). In reversible injury, cells and intracellular organelles typically become swollen because they take in water as a result of the failure of energy-dependent ion pumps in the plasma membrane, leading to an inability to maintain ionic and fluid homeostasis. In some forms of injury, degenerated organelles and lipids may accumulate inside the injured cells.
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  **Fig. shows: Reversiblecell injury and necrosis.
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  • MORPHOLOGY The twomain morphologic correlates of reversible cell injury are cellular swelling and fatty change. • Cellular swelling is commonly seen in cell injury associated with increased permeability of the plasma membrane. When it affects many cells in an organ, it causes pallor (as a result of compression of capillaries), increased turgor, and increase in organ weight. Microscopic examination may show small, clear vacuoles within the cytoplasm; these represent distended and pinched-off segments of the endoplasmic reticulum (ER).This pattern of nonlethal injury is sometimes called hydropic change or vacuolar degeneration. • Fatty change is manifested by the appearance of triglyceride containing lipid vacuoles in the cytoplasm. It is principally encountered in organs that are involved in lipid metabolism, such as the liver, The cytoplasm of injured cells also may become redder (eosinophilic), a change that becomes much more pronounced with progression to necrosis Other intracellular changes associated with cell injury (Fig. shows) include (1) plasma membrane alterations such as blebbing, blunting, or distortion of microvilli, and loosening of intercellular attachments; (2) mitochondrial changes such as swelling and the appearance of phospholipid-rich amorphous densities; (3) dilation of the ER with detachment of ribosomes and dissociation of polysomes; and (4) nuclear alterations, such as clumping of chromatin. The cytoplasm may contain so-called “myelin figures,” which are collections of phospholipids resembling myelin sheaths that are derived from damaged cellular membranes….
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  • Cell Death Whencells are injured they die by different mechanisms, depending on the nature and severity of the insult. • Severe disturbances, such as loss of oxygen and nutrient supply and the actions of toxins, cause a rapid and uncontrollable form of death that has been called “accidental” cell death. • The morphological appearance of accidental cell death is necrosis (Greek, necros = death) • Necrosis is the major pathway of cell death in many commonly encountered injuries, such as those resulting from ischemia, exposure to toxins, various infections, and trauma… • {Table 2.1 Features of Necrosis and Apoptosis]
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  • Necrosis: Necrosis isa form of cell death in which cellular membranes fall apart, and cellular enzymes leak out and ultimately digest the cell. Necrosis produces a local host reaction, called inflammation, that is induced by substances released from dead cells and which serves to eliminate the debris and start the subsequent repair process. • The enzymes responsible for digestion of the cell are derived from lysosomes and may come from the dying cells themselves or from leukocytes recruited as part of the inflammatory reaction. Necrosis often is the culmination of reversible cell injury that cannot be corrected. *Necrosis is characterized by changes in the cytoplasm and nuclei of the injured cells: Cytoplasmic changes. When enzymes have digested cytoplasmic organelles, the cytoplasm becomes vacuolated and appears “moth-eaten. **Apoptosis: A type of cell death in which a series of molecular steps in a cell lead to its death.