Cell Adaptation, Cell Injury and Cell Death Pathology:- is the study of structural and functional abnormalities that are expressed as diseases of organs and systems. Modern pathology, proposed that injury to the smallest living unit of the body, the cell, is the basis of all disease. The plasma membrane establish a structural and functional barrier between its internal milieu and a hostile environment. in several ways: 1-It maintains a constant internal ionic composition against very large chemical gradients between the interior and exterior compartments. 2- It selectively admits some molecules while excluding or extruding others. 3- It provides a structural envelope to contain the informational, synthetic and catabolic - constituents of the cell. 4- It provides an environment to house signal transduction molecules that mediate communication between the external and internal milieus. At the same time, to survive, a cell must be able to adapt to adverse environmental conditions, such as changes in temperature, solute concentrations or oxygen supply, cells encounter many stresses because of changes in their internal and external environments, and this patterns of response to such stresses comprise the cellular basis of disease. 1-Reactions to Persistent Stress and Cell Injury: *Reduced Functional Demand *Inadequate Supply of Oxygen *Insufficient Nutrients *Interruption of Trophic Signals *Persistent Cell Injury *Increased Pressure *Aging *Chronic Disease Cell injury (cell death): it is the variable changes in morphological and functional properties of cell occurs due to internal or external causes (ex. Chemical, physical, infectious and genetic agents), that obligate cell to respond for preserving normal hemostasis (adaptation) or death (necrosis) when the injury factors sever cell unable to 1
adept, cell may also killed by another pathway even when it have the ability to adept for saving other cells and tissue by programed cell death (apoptosis). Mechanisms and Morphology of Cell Injury: All cells have efficient mechanisms to deal with shifts in environmental conditions. Thus, ion channels open or close, harmful chemicals are detoxified, metabolic stores such as fat or glycogen may be mobilized and catabolic processes lead to the segregation of internal particulate materials. Types of cell damages: 1-Reversable (adaptable) (fatty change, cellular swelling). 2-Irreversable (non-adaptable) (necrosis, apoptosis). A) Adaptation: 1-Atrophy:- Is an Active Response to an Altered Environment That Results in Reduced Function orsize of Cells or Organs, atrophy is often noted as decreased size or function of an organ, which may occur under both pathologic and physiologic circumstances. Adipose tissue and skeletal muscle, which respond rapidly to changes in demand for energy storage and contractile force, respectively. When a muscle is immobilized and the need for contraction decreases ( unloading ), myocytes institute selective adaptive mechanisms include: Protein synthesis: Shortly after unloading, protein synthesis Decreases Protein degradation: Particular ubiquitin-related specific protein degradation pathways Gene expression: There are selective decreases in transcription of genes Signaling: The checks and balances that control the levels of upregulation and downregulation of intracellular signaling species change. Energy utilization: A selective decrease 2
2-Hypertrophy Is an Increase in Cell Size and Functional Capacity, When trophic signals or functional demand increases, adaptive changes to satisfy these needs lead to increased cellular size (hypertrophy) and, in some cases, increased cellular number (hyperplasia). Mechanisms of Cellular Hypertrophy *Cellular Remodeling in Hypertrophy: enhanced proteasomal degradation *Signaling Mechanisms in Hypertrophy: many types of signaling may lead to cell hypertrophy 3-Hyperplasia Is an Increase in the Number of Cells in an Organ or Tissue. Hormonal Stimulation: Changes in hormone concentrations can elicit proliferation of responsive cells. 4-Metaplasia Is conversion of one differentiated cell type to another. usually an adaptive response to chronic injury, persistent and usually fully reversible. 5-Dysplasia Is Disordered Growth and Maturation of the Cellular Components of a Tissue, it is a preneoplastic lesion, in that it is a necessarystage in the multistep cellular evolution to cancer. 6-Calcification May Occur as Part of Normal Development or as a Reflection of an Abnormal Process, Metastatic calcification reflects deranged calcium metabolism, in contrast to dystrophic calcification, which has its origin in cell injury. 7-Hyaline Refers to any material that has a reddish, homogeneous appearance when stained with Hematoxylin and Eosin. 8-Hydropic Swelling Is a reversible increase in cell volume, characterized by a large, pale cytoplasm and a normally located nucleus reflects acute reversible cell injury. Subcellular changes include Endoplasmic reticulum, Mitochondria, Plasma membrane and Nucleus. 9-Fatty change: accumulation of fat and triglyceride in cellular cytoplasm, sever fatty changer can effect cellular function. 10-Ischemic Cell Injury Usually Results From Obstruction to the Flow of Blood 3
Oxidative Stress Is a key trigger for cell injury and adaptive responses. Included Reactive Oxygen Species (OH), Hydroxyl Radical H2O2 with ferrous iron (Fe2_), Peroxynitrite interaction of two free radicals, The effectiveness of cellular defenses against oxygen free radicals may determine the outcome of oxidative injury it depends on * Detoxifying Enzymes * Scavengers of ROS 11-Mutations my impair cell function without causing cell death 12-Intracellular storage is retention of materials within the cell (Nutrients, Degraded phospholipids, Substances that cannot be metabolized, Overload of normal body constituents, Abnormal proteins/ ex. Fat, Glycogen, Inherited Lysosomal Storage Diseases, Cholesterol, Abnormal Proteins, Lipofuscin, Melanin, Exogenous Pigments eg. Anthracosis refers to the storage of carbon particles in the lung and regional lymph nodes) B)-Cell Death (Necrosis) Stages of necrosis:- 1-pyknosis; clumping of chromosomes and shrinking of the nucleus of the cell, 2-karyorrhexis; fragmentation of the nucleus and break up of the chromatin into unstructured granules 3-karyolysis; dissolution of the cell nucleus Necrotic Cell Death results from exogenous cell injury and is reflected in geographic areas of cell death. 1-Coagulative necrosis is a morphologic term that refers to light microscopic alterations in dead or dying cells shortly after a cell s death, its outline is maintained. 2-Liquefactive Necrosis when the rate of dissolution of necrotic cells is considerably faster than the rate of repair 4
3-Fat necrosis specifically affects adipose tissue and most commonly results from pancreatitis or trauma. The unique feature determining this type of necrosis is the presence of triglycerides in adipose tissue. 4-Caseous necrosis is characteristic of tuberculosis, in caseous necrosis, unlike coagulative necrosis, the necrotic cells fail to retain their cellular outlines. 5-Fibrinoid Necrosis is an alteration of injured blood vessels, in which insudation and accumulation of plasma proteins cause the wall to stain intensely with eosin. Cells May Participate Actively in their own death (apoptosis) Apoptosis is a form of cellular suicide in which the cell participates actively in its own demise. a mechanism by which individual cells utilize their own signaling systems to sacrifice themselves for the preservation of the organism. removal of apoptotic cells by Tissue Macrophages occurs without an inflammatory reaction. Apoptosis participates in developmental and physiologic processes, deletes mutant cells, defense against dissemination of Infection. 5
Qestions:- 1-Define pathology, cell injury, cellular necrosis, apoptosis. 2-Enumerate five reactions to persistent stress and cell injury. 3- Enumerate five cellular adaptable changes and discuss one. 4- Enumerate five cellular non-adaptable changes and discuss one. 5-Write briefly with draw the stages of necrosis. 6- The effectiveness of cellular defenses against oxygen free radicals may determine the outcome of oxidative injury it depends on. 7- Refers to any material that has a reddish, homogeneous appearance when stained with Hematoxylin and Eosin. 8- In necrosis cellular outline is maintained. 9- necrosis fail to retain their cellular outlines. 10- In necrosis the dissolution faster than repairing. 6