Introduction to Pathology: Cellular Adaptations, Injury, and Death PDF

Faculty of veterinary system Veterinary medicine program Introduction to Pathology Cellular Adaptations, Injury, and Death Dr: Mohamed M.M. Metwally Date: -/-/2024 Professor of Veterinary Pathology  What is pathology? ❑ Pathology is the study (logos) of suffering (pat...

Faculty of veterinary system Veterinary medicine program Introduction to Pathology Cellular Adaptations, Injury, and Death Dr: Mohamed M.M. Metwally Date: -/-/2024 Professor of Veterinary Pathology  What is pathology? ❑ Pathology is the study (logos) of suffering (pathos). ❑ Pathology is focused on the study and diagnosis of diseases. ❑ Pathology provides the scientific foundation for the practice of medicine. ❑ Why do we study pathology? - Pathology is the bridge between science and medicine. It underpins every aspect of patient care, from diagnostic testing and treatment advice to using cutting-edge genetic technologies and preventing disease. - In the last 100 years, we’ve seen significant reductions in illnesses such as polio and major advances in blood transfusion, vaccination, and treatment of inherited conditions. This is all thanks to the pioneering work of pathologists ❑ Aspects of a disease process that form the core of pathology 1. The cause (etiology) 2. Pathogenesis 3. Morphologic changes 4. Functional disorders and stepwise process of the structural changes clinical significance disease development characteristic of the the clinical signs, course, disease and prognosis of the disease. ❑ Causes of cellular adaptation, injury, and death 1. Infectious agents; bacteria, viruses, fungi, and parasites 2. Physical irritants; e.g., extremes of temperature, ionizing radiation, heatstroke, mechanical trauma, sudden change in atmospheric pressure, radiation, and electric shock. 3. Chemical irritants; e.g., caustic agents, poisons, venom, environmental pollutants, alcohol, and drug abuse. 4. Hypoxia, and anoxia; e.g., lack of blood supply (ischemia) or inadequate oxygenation of the blood. 5. Nutritional imbalances; e.g., protein, and vitamin deficiencies, and nutritional excesses 6. Endogenous causes; e.g., genetic defects, hypersensitivity, and autoimmune reactions Response of cells to stresses and stimuli In response to excessive physiologic stresses or certain pathologic stimuli, normal cells can adapt by altering their function, size, and/or number. If the limits of the adaptive capability are exceeded, or if the adaptive response is not possible, cell injury (damage or even death) is carried out. This cell injury is reversible to a certain point. If the stimulus persists or is severe enough from the beginning, the cells reach the point of no return and suffer irreversible cell injury and cell death. o Reversible injury (degeneration): is the injury that can be reversed; normal cellular function is restored. o Irreversible injury: is a permanent pathologic change and may result in cell death. ❑ Cellular adaptations are reversible functional and structural responses to excessive physiologic stresses and some pathologic stimuli allowing the cell to survive and continue to function. o The cells can adapt through the following processes: 1. Atrophy is a decrease in the size of cells after reaching their normal mature size. 2. Hypertrophy is the increase in the size of cells. 3. Hyperplasia is the increase in the number of cells. 4. Metaplasia is the change of one type of basic tissue to another type of the same basic tissue. e.g., the transformation of simple squamous epithelium to stratified squamous epithelium. 5. Dysplasia is the morphologic abnormality in the shape, size, and/or orientation of cells. Examples of reversible cell injury 1. Cell swelling (cloudy swelling, vacuolar and hydropic degenerations): occurs when the regulatory mechanisms that control the normal ionic balance of a cell fail, and sodium and water enter the cell. 2. Fatty change (lipidosis, steatosis) abnormal intracellular accumulation of neutral fat (triglycerides) in non-fatty tissue, particularly in the liver. The main causes include increased mobilization of lipids from adipose tissue, impaired removal or increased synthesis of fatty acids by the liver, and reduced formation or secretion of lipoproteins Normal liver Fatty liver  Cell death It is the permanent loss of cellular functions associated with irreversible structural changes This may occur through several mechanisms including, but not exclusive to: - 1) Apoptosis: Programmed cell death. 2) Necrosis: Pathological unregulated cell death within the living body. 3) Necroptosis: regulated necrosis often triggered by TNF-alpha or other death ligands. 4) Pyroptosis: Inflammasome-mediated cell death with inflammatory consequences, often triggered by pathogens or danger signals. It occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. 5) Ferroptosis/Oxytosis: Iron-dependent regulated cell death triggered by oxidative stress, characterized by iron and lipid peroxidation product accumulation. ▪ Autophagy: Cellular self-digestion, where cells degrade and recycle their own components. It can delay or prevent cell death or promote it under certain conditions. ▪ Somatic death (biological death) is the irreversible cessation of all vital functions of an organism, including the heart, lungs, and brain. It is the biological end of life.  Apoptosis (cellular suicide) ▪ Apoptosis is an evolutionarily conserved cell death pathway that is responsible for the proper culling of cells during normal development and the maintenance of homeostasis The morphological features of apoptosis 1- Shrinkage of the cell (cytoplasmic and nuclear condensation) 2- Blebbing of the cell membrane 3- Fragmentation of the nucleus 4- Fragmentation into membrane-bound apoptotic bodies 5- Phagocytosis by neighboring cells  Types of apoptosis A. Physiological 1. Normal cells at the end of their life span. e.g., erythrocytes death (eryptosis). 2. Hormone-dependent tissues as milk-producing epithelial cells in the mammary gland after lactation. B-Pathological 1- Cells infected with viruses. 2- Cells of the immune system. The effector cells must be removed to prevent them from attacking body constituents. (Any defect in the apoptotic machinery is associated with autoimmune diseases). 3- Cells with DNA damage. (Cells respond to DNA damage by increasing their production of P53; a potent inducer of apoptosis). 4- Cancer cells; Radiation and chemicals used in cancer therapy induce apoptosis.  Necrosis The morphological features of necrosis 1- Cellular swelling: due to swelling of organelles, such as the endoplasmic reticulum and mitochondria 2. Nuclear changes a- Pyknosis: shrinkage of the nucleus (the nucleus appears small and very dark). b- Karyorrhexis: fragmentation of the nucleus into numerous granules. c- Karyolysis: lysis of the chromatins (nucleus just fades away) 3- Loss of cellular membrane integrity 4- Leakage of the cellular contents 5- Immune response (inflammation).  Main differences between apoptosis, and necrosis Apoptosis Necrosis ▪ Physiological or pathological ▪ Always pathological ▪ Single cell affected ▪ Group of cells affected ▪ Energy dependent ▪ Energy independent ▪ Cell shrinkage ▪ Cell swelling ▪ Blebbing of the cell membrane ▪ Loss of cellular membrane integrity ▪ Formation of apoptotic bodies ▪ Leakage of the cellular contents ▪ Phagocytosis by neighboring cells ▪ Phagocytosis of the necrotic cells by (no inflammation) immune cells (inflammation)  Types of necrosis (morphological patterns of necrosis) 1. Coagulative necrosis Results from denaturation of cellular proteins. Characterized microscopically by maintenance of tissue architecture (for at least a couple of days) and loss of cellular details. Most are seen in ischemic, hypoxic, and toxemic conditions. Normal testis Coagulative necrosis in testis 2. Liquefactive necrosis - Results from enzymatic digestion of cells. Microscopically, characterized by transformation of the tissue into a liquefied, or liquid-filled cavity. Mostly seen with a pyogenic bacterial infection. e.g., abscesses (pus appears microscopically as basophilic structureless material), and in necrotic brain tissue (appears microscopically as empty spaces). 3. Caseous necrosis - Is a combination of coagulative and liquefactive necrosis. The dead cells disintegrate but are not completely digested. It is characterized by the transformation of the tissue into friable, dry, and slightly greasy cheese-like material. Microscopically, the caseous material appears as eosinophilic, and basophilic debris (a mixture of coagulated protein and lipid). Most are seen with certain pathological conditions such as TB, and certain fungal infections (histoplasmosis, cryptococcosis, and coccidioidomycosis). 4. Fat necrosis: - It is the necrosis of adipose tissue, resulting from the release of stored triglycerides in the adipocytes and its breakdown by lipases into fatty acids and glycerol (absorbed). The fatty acids may combine with ions like sodium, potassium, and calcium. Types of fat necrosis 1. Pancreatic fat necrosis (internal or abdominal): occurs only in the abdominal cavity as a result of fat-splitting by pancreatic lipase due to injury, rupture, or inflammation of the pancreas. 2. Traumatic fat necrosis (external): occurs in the subcutaneous and intermuscular fat. Where the lipase enzyme is liberated after traumatic injury. ▪ Grossly the affected part may be bright yellow (saponification), yellow-gray (fibrosis), or chalky white (calcification). Fat necrosis: ▪ Microscopically, early lesions show non- nucleated adipocytes, foamy (lipid-laden) macrophages, and sometimes multinucleated giant cells. Older lesions develop fibrosis with a few foamy macrophages, multinucleated giant cells, and sometimes dystrophic calcification 5. Gangrenous necrosis - Gangrene is a massive ischemic tissue necrosis. It may be ❑ Dry gangrene (coagulative necrosis) occurs when the blood supply to tissue is cut off. The area becomes dry, shrinks, and turns black. ❑ Wet gangrene (moist gangrene) (liquefactive necrosis) occurs if bacteria invade this tissue. This makes the area swell, drain fluid, and smell bad.