Cell Injury-1 PDF

# Cell Injury-1 ## ALMAARefa University, College of Medicine Dr. Gehan Abdelmenam ## Intended Learning Objectives - List causes of cell injury. - Describe forms of Adaptation with an example for each. - Recall types of cell injury. - Describe mechanisms and morphology of reversible cell injury....

# Cell Injury-1 ## ALMAARefa University, College of Medicine Dr. Gehan Abdelmenam ## Intended Learning Objectives - List causes of cell injury. - Describe forms of Adaptation with an example for each. - Recall types of cell injury. - Describe mechanisms and morphology of reversible cell injury. - Recall definition, causes, and consequences of hypoxic cell injury - Describe mechanisms of irreversible cell injury. ## Introduction - Cells are constantly exposed to a variety of stresses. - Cells try to adapt themselves to overcome a stressful condition. - When stress is severe or of prolonged duration, cell injury results. ## Causes of Cellular Injury - **Physical Agents** - Hypoxia - Mechanical trauma - Burns - Radiations - Electric shock - **Chemical Agents** - Poisons (toxins) - Insecticides - Alcohol - Tobacco. - **Infectious Agents** - Viruses - Bacteria - Fungi - Parasites. - **Immunologic Reactions** - Anaphylaxis - Autoimmune disease. - **Genetic Derangements** - Abnormal proteins (Hemoglobinopathies). - Abnormal or absent enzymes (storage disorders). ## Adaptation - **Hyperplasia:** Increase in cell number, for example: compensatory hyperplasia of the kidney after nephrectomy. - **Hypertrophy:** Increase in cell size. An Example is the left ventricle due to aortic stenosis or systemic hypertension. - **Atrophy:** Decrease in cell number and/or size. An Example is skeletal muscle atrophy after paralysis. - **Metaplasia:** Change of one type of cell to another type of the same category. For example, epithelial to epithelial or connective tissue to connective tissue, for example: | Tissue | Normal | Metaplasia | Stimulus | | --------------- | ----------------------- | --------------------- | ----------------------------- | | Airways | Pseudostratified columnar epithelium | Squamous epithelium | Cigarette smoke | | Urinary bladder | Transitional epithelium | Squamous epithelium | Bladder stone | | Esophagus | Squamous epithelium | Columnar epithelium | Gastro-esophageal reflux (Barrett's Esophagus) | | Endocervix | Columnar epithelium | Squamous epithelium | Hormonal changes | - An illustration of this type of cell adaptation can be seen in the airways. There is a change from the normal ciliated columnar epithelium lining bronchi and bronchioles to stratified squamous epithelium. - This is usually in response to chronic irritation, such as cigarette smoke. ## Cell Injury - **Cell Injury may be:** - **Reversible:** If the affected cells can recover from the injury. - **Irreversible:** If the affected cell dies. ## Reversible Cell Injury - **Mechanisms of Reversible Cell Injury:** - **There is a disturbance in the function of:** - **Cell Membrane:** Leading to loss of structural integrity and loss of function. - **Mitochondria:** Leading to decreased energy production (decrease ATP). - **Ribosomes:** Leading to decreased protein synthesis. - **Accumulation of Oxygen Derived Free Radicals:** For example, Hydrogen peroxide. ## Hypoxic Cell Injury - The most common cause of cell injury. - **Definition:** Inadequate oxygenation of tissue. - **Causes:** - **Hypoxemia:** Decrease in the amount of oxygen dissolved in the plasma. - **Hemoglobin Related Abnormalities:** Anemia. - **Ischemia:** Decreased arterial blood flow to tissues. Usually due to atherosclerosis. ## Consequences of Tissue Hypoxia - Decreased synthesis of ATP by oxidative phosphorylation causing ATP depletion. - This leads to: - **Impaired Na+/K+-ATPase pump:** Diffusion of Na+ and water into cells, resulting in cellular swelling. - **Shifting to Anaerobic Glycolysis:** Leads to accumulation of lactic acid. Decrease in intracellular pH leads to denaturation of proteins. Decreased activity of many enzymes leads to clumping of nuclear chromatin. - **Ribosomal Detachment:** Leads to decreased protein synthesis. Decreased protein synthesis leads to decreased synthesis of apolipoproteins (lipid carriers in the blood), resulting in accumulation of lipid in the cell (fatty change). ## Morphology of Reversible Cell Injury - **Cell Swelling:** - The first manifestation of cell injury. - Occurs when cells fail to maintain ionic and fluid homeostasis. - Manifests as small clear vacuoles inside the cytoplasm. - Also known as hydropic change. - **Fatty Change:** - Manifested by the appearance of lipid vacuoles in the cytoplasm. - Seen in the kidney, heart, and liver. ## Irreversible Cell Injury - **Mechanism of Irreversible Cell Injury:** - Persistent or severe injury (severe hypoxia or anoxia) takes the cell to the "point of no return" where the injury becomes irreversible. - At this point, no intervention can save the cell. - Severe mitochondrial damage is the hallmark of irreversible injury. ## Mitochondrial Damage - Marked reduction in ATP production leads to mitochondrial damage. - This results in the formation of high conductance channels (mitochondrial permeability transition (MPT) channels). - This results in the release of cytochrome c into the cytosol, which is a trigger for cell death. ## References - Robbins and Cotran Pathologic Basis of Disease, 9th edition, 2014 (Kumar, Abbas, Aster) - Robbins Basic Pathology 10th edition, 2017 (Kumar, Abbas, Aster)