PHTH1012 002 Cell Pathology.pdf

Cell Pathology MORPHOLOGY Learning Outcomes Describe Normal structure and function of cells Describe fully the cause and process of cell and tissue damage The Normal Cell Normal Cell structure  Cell Membrane  Nucleus  Cytosol and Organelles Endoplasmic reticulum  Mitochondria  Golgi Apparatus...

Cell Pathology MORPHOLOGY Learning Outcomes Describe Normal structure and function of cells Describe fully the cause and process of cell and tissue damage The Normal Cell Normal Cell structure  Cell Membrane  Nucleus  Cytosol and Organelles Endoplasmic reticulum  Mitochondria  Golgi Apparatus Function Of Cells  Energy Production  Protein Synthesis  Cellular Communication  Homeostasis Maintenance  Immune Response Why should we care? CELL INJURY Cell Injury  The onset of structural and functional alterations caused by pathology initiates with cellular injury within the tissues. Cell injury can be:  Reversible (non-lethal)  Irreversible (lethal)  Aetiology of Cell Injury           Hypoxia & Ischemia Physical Agents Chemical Agents & Drugs Microbial Agents Immunological Agents Nutritional Derangements Aging Psychogenic Diseases Iatrogenic Factors Idiopathic Diseases Pathogenesis of Cell Injury  Type / Duration / Severity of Injurious Agent  Type / Status / Adaptability of Target Cells  Underlying Intracellular Phenomena  Morphologic Consequences Common examples of morphologic changes of Reversible Cell Injury:  Hydropic Change  Fatty Change  Hyaline Change  Mucoid Change Hydropic Change Hydropic change means accumulation of water within the cytoplasm of the cell. Other synonyms used are cloudy swelling (for gross appearance of the affected organ) and vacuolar degeneration (due to cytoplasmic vacuolation). Fatty Change  Fatty change, steatosis or fatty metamorphosis is the intracellular accumulation of neutral fat within parenchymal cells.  The deposit is in the cytosol and represents an absolute increase in the intracellular lipids.  It is especially common in the liver but may occur in other non-fatty tissues like the heart, skeletal muscle, kidneys (lipoid nephrosis or minimum change disease) and other organs. Reversible Cell InjuryStructural Alterations  Changes in Membrane Integrity:  Structural Alterations:  Disturbances in the lipid bilayer and protein components of the cell membrane.  Potential formation of membrane blebs and irregularities in membrane structure. Reversible Cell InjuryStructural Alterations  Organelle Abnormalities:  Mitochondria:  Functional Impact: Impaired oxidative phosphorylation affecting ATP production.  Structural Changes: Swelling of the mitochondrial matrix. Reversible Cell InjuryStructural Alterations  Endoplasmic Reticulum (ER): Functional Impact: ER stress affecting protein folding and synthesis. Structural Changes: Distension and dilation of the ER cisternae.  Golgi Apparatus: Functional Impact: Altered processing and trafficking of proteins. Structural Changes: Disorganization and fragmentation of Golgi stacks. Reversible Cell Injury- Structural Alterations  Cytoplasmic Changes:  Granularity:  Microscopic Features: Increased granularity visible under light microscopy.  Composition: Aggregation of organelles, proteins, or cellular debris contributing to granularity.  Vacuolization:  Microscopic Features: Formation of vacuoles within the cytoplasm.  Mechanism: Accumulation of cellular substances or water-filled vesicles. Reversible Cell Injury- Structural Alterations  Nuclear Morphology:  Preservation of Nuclear Structure: Nucleus typically maintains its integrity, ensuring the preservation of genetic material. Chromatin remains relatively unaltered, allowing for potential recovery. Reversible Cell Injury Response  Inflammatory Responses:  Mild Inflammatory Mediator Release:  Release of cytokines, chemokines, and other mediators in response to cellular stress.  Recruitment of immune cells to the site of injury, aiming at removal of the stressor. Cellular Adaptations-Chronic Cell injury Atrophy Cellular AdaptationsChronic Cell injury Hypertrophy Hyperplasia Metaplasia Dysplasia Atrophy Reduction of the number and size of parenchymal cells of an organ or its parts which was once normal is called atrophy. Atrophy may occur from physiologic or pathologic causes. Hypertrophy is an increase in the size of parenchymal cells resulting in enlargement of the organ or tissue, without any change in the number of cells. Hypertrophy may be physiologic or pathologic. Hypertrophy In both cases, it is caused either by increased functional demand or by hormonal stimulation. Hypertrophy without accompanying hyperplasia affects mainly muscles. Hyperplasia Hyperplasia is an increase in the number of parenchymal cells resulting in enlargement of the organ or tissue. Quite often, both hyperplasia and hypertrophy occur together. All body cells do not possess hyperplastic growth potential. Hyperplasia    Cells that can undergo hyperplasia: Labile cells (e.g. epithelial cells of the skin and mucous membranes, cells of the bone marrow and lymph nodes) and Stable cells (e.g. parenchymal cells of the liver, pancreas, kidney, adrenal, and thyroid),  NOT  Permanent cells (e.g. neurons, cardiac and skeletal muscle) have little or no capacity for regenerative hyperplastic growth.  Metaplasia is a reversible and adaptive cellular change in which one mature cell type is replaced by another mature cell type, often in response to chronic irritation, inflammation, or stress.  This process involves the transformation of one specialized cell type into another that is better suited to withstand the challenging environment.  However, if the stimulus persists for a long time, epithelial metaplasia may transform into cancer.  Metaplasia is broadly divided into 2 types: epithelial and mesenchymal. Metaplasia Dysplasia  Dysplasia means ‘disordered cellular development’, often accompanied with metaplasia and hyperplasia; it is therefore also referred to as atypical hyperplasia.  Dysplasia occurs most often in epithelial cells.  Epithelial dysplasia is characterised by cellular proliferation and cytologic changes. Irreversible Cell Injury & Cell Death Irreversible Cell InjuryStructural Alterations  Cellular Membrane Damage: Description: Severe disruption of the cell membrane integrity. Mechanism: Extensive membrane damage leads to leakage of intracellular contents and loss of cellular boundaries. Irreversible Cell InjuryStructural Alterations  Organelle Breakdown:  Mitochondrial Damage:  Description: Severe structural and functional impairment, including mitochondrial swelling and loss of cristae.  Consequence: Irreversible damage to the powerhouse of the cell, impacting ATP production.  Nuclear Changes:  Description: Condensation of chromatin, nuclear fragmentation (karyorrhexis), or complete dissolution of the nucleus (karyolysis).  Consequence: Loss of nuclear integrity, preventing cellular recovery. Irreversible Cell Injury- Structural Alterations  Cytoplasmic Changes:   Formation of Cytoplasmic Vacuoles:  Description: Large vacuoles containing cellular debris.  Mechanism: Accumulation of degraded organelles and proteins, indicative of cellular degradation. Amorphous Densities:  Description: Aggregation of dense, amorphous material in the cytoplasm.  Consequence: Sign of advanced cellular damage and disruption of normal cellular composition. Apoptosis Morphology of Cell Death Necrosis Gangrene Pathologic Calcification Apoptosis  Apoptosis is a form of ‘coordinated and internally programmed cell death’ having significance in a variety of physiologic and pathologic conditions.  A form of cell death which is controlled and regulated by the rate of cell division; when the cell is not needed, pathway of cell death is activated (‘cell suicide’) and is unaccompanied by any inflammation and collateral tissue damage. Necrosis  Necrosis is defined as a localised area of death of tissue followed by degradation of tissue by hydrolytic enzymes liberated from dead cells; it is invariably accompanied by inflammatory reaction. Necrosis  Morphological Changes:  Cell Swelling (Oncosis):  Description: Necrosis often involves cellular swelling, a condition known as oncosis, leading to an increase in cell volume.  Consequence: The swelling contributes to the overall enlargement of affected cells. Necrosis  Rupture of Cell Membrane: Description: Necrotic cells experience disruption of the cell membrane, leading to leakage of cellular contents into the extracellular space. Consequence: This rupture contributes to inflammation in the surrounding tissue. Necrosis  Inflammatory Response:  Release of Cell Contents:  Description: Necrosis results in the release of cellular contents, including enzymes, proteins, and other intracellular molecules, into the extracellular matrix.  Consequence: This release triggers an inflammatory response as the immune system responds to clear cellular debris and damaged tissue. Types of Necrosis  Coagulative Necrosis  Liquefaction Necrosis  Caseous Necrosis  Fat Necrosis  Fibrinoid Necrosis Types of Necrosis Causes Effects on the Cell Typical Areas of Involvement Coagulative Necrosis - Ischemia (lack of blood supply) - Infarction (tissue death due to blood vessel blockage) - Denaturation of cellular proteins, loss of cell structure - Preservation of tissue architecture for a period - Gradual replacement by scar tissue -Heart, kidney, spleen, solid organs. Liquefactive Necrosis - Bacterial or fungal infections - Abscess formation - Rapid breakdown of cells, formation of liquid mass - Formation of pus within affected areas - Potential tissue liquefaction and cavity formation - Brain (abscess formation), areas of bacterial infection Caseous Necrosis - Tuberculosis (granulomatous infections) - Fungal infections - Formation of cheeselike, amorphous mass - Distinctive appearance under microscopy - Lungs (associated with tuberculosis), lymph nodes Types of Necrosis Causes Effects on the Cell Typical Areas of Involvement Fatty Necrosis - Trauma or inflammation affecting adipose tissue - Pancreatitis - Breakdown of fat cells, formation of chalky white areas - Inflammation of surrounding tissue -Breast, Pancreas Fibrnoid Necrosis - Trauma to blood vessel wall - Formation of fibrinlike material in vessel walls - Blood vessels, particularly in autoimmune disorders Gangrene  Gangrene is a form of necrosis of tissue with superadded putrefaction.  The type of necrosis is usually coagulative due to ischaemia (e.g.in gangrene of the bowel, gangrene of limb).  It is characterised by primarily inflammation provoked by virulent bacteria resulting in massive tissue necrosis.  The end-result of necrotizing inflammation and gangrene is the same but the way the two are produced, is different. Gangrene  2 main forms of gangrene:  Dry and  Wet, and a variant form of wet gangrene called gas gangrene.  In all types of gangrene, necrosis undergoes liquefaction by the action of putrefactive bacteria. Pathologic Calcification  Deposition of calcium salts in tissues other than osteoid or enamel is called pathologic or heterotopic calcification.  Dystrophic Calcification   Deposition of calcium salts in an area of damaged tissue. Can occur in soft tissue.  Eg calcific tendinitis Metastatic calcification  Occurs with hypercalcemia Aetiology of Cell Injury           Hypoxia & Ischemia Physical Agents Chemical Agents & Drugs Microbial Agents Immunological Agents Nutritional Derangements Aging Psychogenic Diseases Iatrogenic Factors Idiopathic Diseases Aetiology of Cell Injury   Physical Agents:  Mechanical Trauma: Direct mechanical force can disrupt cell membranes, organelles, and cytoskeleton structures, leading to cell lysis or damage.  Temperature Extremes: Extreme temperatures can alter membrane fluidity, denature proteins, and disrupt cellular structures. Chemical Agents:  Toxins and Poisons: Chemical substances can interfere with cellular functions by disrupting membranes, inhibiting enzymes, or inducing oxidative stress.  Chemical Burns: Corrosive chemicals directly damage cell membranes and proteins, leading to cell death and tissue destruction. Aetiology of Cell Injury  Infectious Agents:   Microorganisms: Pathogens can directly damage cells through invasion, toxin production, or induction of inflammatory responses. Immunological Reactions:  Autoimmune Reactions: In autoimmune diseases, the immune system mistakenly targets and attacks healthy cells, leading to inflammation and tissue damage.  Hypersensitivity Reactions: Excessive immune responses, such as Type II or Type III hypersensitivity, can cause tissue damage through immune complex deposition or direct cell destruction. Aetiology of Cell Injury   Genetic Factors:  Genetic Mutations: Mutations can lead to malfunctioning proteins, disrupted signaling pathways, or abnormal cell cycle regulation, contributing to cell injury.  Genetic Disorders: Inherited genetic disorders can affect cellular metabolism and function, causing cell injury over time. Nutritional Imbalances:  Nutrient Deficiencies: Lack of essential nutrients, such as vitamins and minerals, can impair cellular metabolism and lead to cell dysfunction or death.  Excess Nutrients: Overconsumption of nutrients, especially certain fats and sugars, can contribute to metabolic disorders and cellular damage. Aetiology of Cell Injury   Oxygen Deprivation (Hypoxia):  Ischemia: Reduced blood flow limits oxygen supply, leading to energy depletion, mitochondrial dysfunction, and eventual cell injury or death.  Anoxia: Complete lack of oxygen prevents oxidative phosphorylation, causing rapid ATP depletion and severe cellular damage. Radiation:  Ionizing Radiation: Generates free radicals, causing DNA damage and disrupting cellular structures. Leads to cell cycle arrest, apoptosis, or potential initiation of cancer.  Ultraviolet (UV) Radiation: Causes DNA damage, particularly in skin cells, leading to mutations and increasing the risk of skin cancer. Aetiology of Cell Injury  Inflammatory Responses:  Chronic Inflammation: Prolonged release of inflammatory mediators, such as cytokines and reactive oxygen species (ROS), contributes to tissue damage and cell injury.  Autoimmune Inflammation: Immune cells target and attack healthy tissues, leading to chronic inflammation and tissue destruction. Aetiology of Cell Injury  Psychological Stress:   Chronic Stress: Prolonged stress can dysregulate the immune system, increase inflammation, and contribute to conditions such as cardiovascular disease and immune disorders. Aging:  Cellular Senescence: Accumulation of cellular damage over time, including telomere shortening, oxidative stress, and genetic mutations, contributes to aging-related cell injury and dysfunction. Resources  Miller MA, Zachary JF. Mechanisms and Morphology of Cellular Injury, Adaptation, and Death. Pathologic Basis of Veterinary Disease. 2017:2–43.e19. doi: 10.1016/B978-0-323-35775-3.00001-1. Epub 2017 Feb 17. PMCID: PMC7171462.  Pathology : implications for the physical therapist (Fourth). (2015).. Elsevier Saunders.  Pathology illustrated (Eighth). (2018).. Elsevier. END