Pathophysiology is the study of abnormal functions or breakdown of homeostasis in diseases. It examines the mechanisms by which lesions are produced and their functional implications. Key events in the history of pathophysiology include Hippocrates introducing ethical medicine, Galen proposing the humoral theory, and advances in microscopy and staining techniques in the 19th century enabling the study of cells and microorganisms. Major developments in the 20th century included identifying DNA as the genetic material, cloning animals, and completing the Human Genome Project to sequence the entire human genome.
Pathology is the scientific study of disease through examination of tissues and cells. Key terms include:
- Pathology examines structural and functional changes in disease (pathophysiology examines disordered function).
- Disease is a condition causing discomfort, while illness is one's reaction to disease through symptoms and signs.
- Syndromes describe combinations of symptoms from altered physiology. Important tissues include lesions in patients and pathologic changes seen macroscopically and microscopically. Etiology examines causal factors and pathogenesis examines how lesions are produced.
The document discusses cellular responses and adaptations to stress and injury. It provides an overview of how normal cells require specific environmental conditions to function properly and will try to adapt to changes through processes like hypertrophy, hyperplasia, atrophy and metaplasia. If cells cannot adapt to stress, either reversible or irreversible injury can occur, potentially leading to cell death through necrosis or apoptosis. The mechanisms of cellular injury include oxidative stress, depletion of ATP, calcium dysregulation, and damage to organelles like mitochondria and lysosomes.
This document discusses various types of cellular adaptations: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia. Atrophy is a reduction in cell size and number. Hypertrophy is an increase in cell size but not number. Hyperplasia is an increase in cell number. Metaplasia is a change from one adult cell type to another. Dysplasia refers to abnormal cell shapes and sizes that can progress to cancer. Cellular adaptations provide clues for pathologists to diagnose disease.
Cell injury can occur through various acquired and genetic causes and results in cellular adaptations or cell death. Reversible cell injury causes cellular swelling and fatty change, while irreversible injury leads to necrosis, apoptosis, or autolysis/heterolysis. Necrosis is characterized by loss of membrane integrity and cellular contents, resulting in nuclear changes like pyknosis, karyorrhexis, and karyolysis. In contrast, apoptosis is a programmed form of cell death where the cell activates enzymes to degrade its own DNA and proteins while keeping the plasma membrane intact.
This document discusses the pathology of reactivity and resistance in organisms. It defines reactivity as an organism's ability to alter its functional activity and systems to adapt to new environmental conditions and ensure survival. Resistance is described as an organism's stability when facing pathogenic factors. The document then categorizes and explains the different types of reactivity and resistance, including specific vs nonspecific, active vs passive, primary vs secondary, and more. It also outlines the physiological levels and systems that regulate reactivity, such as the nervous, endocrine, immune, and monocyte-macrophage systems.
1. Tissue repair involves regeneration of injured tissue or replacement by connective tissue scarring. It involves cell proliferation and interaction between cells and the extracellular matrix.
2. Tissues are divided into continuously dividing, stable, and permanent groups based on their ability to proliferate. Continuously dividing tissues like skin regenerate easily while permanent tissues like neurons cannot regenerate after injury.
3. Growth factors and the extracellular matrix play important roles in tissue repair by stimulating cell growth and movement. Repair occurs through regeneration in labile tissues and scarring in others when injury is too severe for regeneration.
This document discusses etiology and pathogenesis of cell injury. It defines cell injury as changes in a cell's internal and external environment due to various stresses from etiological agents. The cellular response depends on host factors like cell type and extent of injury. Injury can result in reversible or irreversible cell injury depending on factors like agent type/duration and cell adaptability. Common causes of cell injury include hypoxia, ischemia, toxins, microbes, nutrition imbalances, and aging. Ischemia and hypoxia are the most frequent causes of cell injury in humans. Reversible injury involves ATP depletion and membrane changes, while irreversible injury brings further damage including to mitochondria and nuclei, leading to cell death.
This document provides an introduction to pathology, outlining key figures in the field and subdivisions of pathology. It defines pathology as the study of structural, biochemical and functional changes in cells, tissues and organs that underlie disease. Pathology is broadly divided into general pathology, which deals with general disease principles, and systemic pathology, which studies diseases pertaining to specific organs and body systems. Systemic pathology includes histopathology, cytopathology, hematology, microbiology, chemical pathology, immunology, experimental pathology, geographic pathology, medical genetics, and molecular pathology.
Pathology is the scientific study of disease through examination of tissues and cells. Key terms include:
- Pathology examines structural and functional changes in disease (pathophysiology examines disordered function).
- Disease is a condition causing discomfort, while illness is one's reaction to disease through symptoms and signs.
- Syndromes describe combinations of symptoms from altered physiology. Important tissues include lesions in patients and pathologic changes seen macroscopically and microscopically. Etiology examines causal factors and pathogenesis examines how lesions are produced.
The document discusses cellular responses and adaptations to stress and injury. It provides an overview of how normal cells require specific environmental conditions to function properly and will try to adapt to changes through processes like hypertrophy, hyperplasia, atrophy and metaplasia. If cells cannot adapt to stress, either reversible or irreversible injury can occur, potentially leading to cell death through necrosis or apoptosis. The mechanisms of cellular injury include oxidative stress, depletion of ATP, calcium dysregulation, and damage to organelles like mitochondria and lysosomes.
This document discusses various types of cellular adaptations: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia. Atrophy is a reduction in cell size and number. Hypertrophy is an increase in cell size but not number. Hyperplasia is an increase in cell number. Metaplasia is a change from one adult cell type to another. Dysplasia refers to abnormal cell shapes and sizes that can progress to cancer. Cellular adaptations provide clues for pathologists to diagnose disease.
Cell injury can occur through various acquired and genetic causes and results in cellular adaptations or cell death. Reversible cell injury causes cellular swelling and fatty change, while irreversible injury leads to necrosis, apoptosis, or autolysis/heterolysis. Necrosis is characterized by loss of membrane integrity and cellular contents, resulting in nuclear changes like pyknosis, karyorrhexis, and karyolysis. In contrast, apoptosis is a programmed form of cell death where the cell activates enzymes to degrade its own DNA and proteins while keeping the plasma membrane intact.
This document discusses the pathology of reactivity and resistance in organisms. It defines reactivity as an organism's ability to alter its functional activity and systems to adapt to new environmental conditions and ensure survival. Resistance is described as an organism's stability when facing pathogenic factors. The document then categorizes and explains the different types of reactivity and resistance, including specific vs nonspecific, active vs passive, primary vs secondary, and more. It also outlines the physiological levels and systems that regulate reactivity, such as the nervous, endocrine, immune, and monocyte-macrophage systems.
1. Tissue repair involves regeneration of injured tissue or replacement by connective tissue scarring. It involves cell proliferation and interaction between cells and the extracellular matrix.
2. Tissues are divided into continuously dividing, stable, and permanent groups based on their ability to proliferate. Continuously dividing tissues like skin regenerate easily while permanent tissues like neurons cannot regenerate after injury.
3. Growth factors and the extracellular matrix play important roles in tissue repair by stimulating cell growth and movement. Repair occurs through regeneration in labile tissues and scarring in others when injury is too severe for regeneration.
This document discusses etiology and pathogenesis of cell injury. It defines cell injury as changes in a cell's internal and external environment due to various stresses from etiological agents. The cellular response depends on host factors like cell type and extent of injury. Injury can result in reversible or irreversible cell injury depending on factors like agent type/duration and cell adaptability. Common causes of cell injury include hypoxia, ischemia, toxins, microbes, nutrition imbalances, and aging. Ischemia and hypoxia are the most frequent causes of cell injury in humans. Reversible injury involves ATP depletion and membrane changes, while irreversible injury brings further damage including to mitochondria and nuclei, leading to cell death.
This document provides an introduction to pathology, outlining key figures in the field and subdivisions of pathology. It defines pathology as the study of structural, biochemical and functional changes in cells, tissues and organs that underlie disease. Pathology is broadly divided into general pathology, which deals with general disease principles, and systemic pathology, which studies diseases pertaining to specific organs and body systems. Systemic pathology includes histopathology, cytopathology, hematology, microbiology, chemical pathology, immunology, experimental pathology, geographic pathology, medical genetics, and molecular pathology.
Pathology is the scientific study of disease through examination of organs, tissues, bodily fluids, and sometimes whole bodies. It involves studying the structural and functional changes caused by disease. Pathologists examine samples through various methods including gross examination, histopathology, immunohistochemistry, and electron microscopy to diagnose disease and understand disease processes and causes. The main subdivisions of pathology are anatomical pathology, clinical pathology, forensic pathology, and neuropathology.
Healing occurs through regeneration or scar formation depending on the cell and injury type. Wound healing follows two main pathways: primary intention for clean surgical wounds where edges are approximated, or secondary intention for wounds with separated edges and more tissue death. The process involves inflammation, granulation tissue formation, re-epithelialization, wound contraction and ECM deposition. Several local and systemic factors can delay healing including infection, poor blood supply, drugs, and nutritional deficiencies.
This document discusses cell injury and cell death. It defines cell injury as a change in cell structure, metabolism or function that impairs its vital activity. Causes of cell injury include internal stresses like metabolic imbalances and external stresses such as physical agents, toxins, and chemicals. Cell injury can be reversible or irreversible and lead to cell death through mechanisms like necrosis, autolysis, or apoptosis. Signs of cell injury include morphological changes, functional impairments, and metabolic derangements. Specific types of cell injury discussed include fatty change, pigmentation, calcification, amyloidosis, and various forms of necrosis.
Cells can adapt to changes in their environment through various processes including hyperplasia, hypertrophy, atrophy, metaplasia, and dysplasia. Hyperplasia is an increase in cell number, hypertrophy is an increase in cell size, and atrophy is a decrease in cell size or number. Metaplasia is a reversible change where one adult cell type replaces another. Dysplasia involves disordered cellular development and proliferation with cytological abnormalities. These adaptations allow cells to survive stresses and ensure tissue homeostasis.
This document discusses different types of cell death known as necrosis. It defines necrosis as irreversible damage to cells that cannot be corrected and involves failure of ATP generation, membrane damage, and damage from reactive oxygen species. The document outlines several patterns of necrosis including coagulative necrosis where tissue architecture is preserved, liquefactive necrosis where tissue turns into a viscous liquid, and caseous necrosis where tissue has a cheesy, yellow-white appearance. It also discusses specific forms of necrosis that can occur in conditions like infections, gangrene, acute pancreatitis, and immune reactions.
Pathological calcification involves the abnormal deposition of calcium salts in tissues other than bone. There are two main types: dystrophic calcification occurs in dead or damaged tissue with normal calcium levels, while metastatic calcification affects normal tissues and results from disorders that increase calcium levels in the blood (hypercalcemia). Dystrophic calcification is seen in areas of necrosis, atherosclerotic plaques, and infarcts. Metastatic calcification commonly involves the kidneys, lungs, blood vessels, and stomach, and is caused by hyperparathyroidism, bone destruction, or excessive vitamin D intake.
This document defines inflammation and describes the key cellular and vascular events involved. Inflammation is the body's response to injury or infection, and involves vascular changes such as increased blood flow and permeability, as well as cellular events like the migration of white blood cells. These events are mediated by chemical signaling molecules called mediators, which help regulate the inflammatory response. The document outlines the major mediators involved and their roles in vascular changes, cellular recruitment, and resolution of inflammation.
This document summarizes different types of reversible cell injury seen microscopically, including hydropic change, hyaline change, mucoid change, and fatty change. Hydropic change is characterized by cytoplasmic vacuolation and swelling of cells. Hyaline change results in a glassy, eosinophilic appearance of intracellular or extracellular proteins. Mucoid change describes excess intracellular or extracellular mucin accumulation. Fatty change or steatosis involves intracellular accumulation of neutral fats within cells. Each type of change is described in detail with examples and microscopic images.
1) Chronic inflammation is inflammation of prolonged duration that can occur following acute inflammation or persistently as active inflammation, often resulting in tissue destruction and repair processes.
2) Causes of chronic inflammation include persistent infections, prolonged exposure to toxic agents, and autoimmunity.
3) Morphological features of chronic inflammation are characterized by infiltration of mononuclear cells like macrophages and lymphocytes, tissue destruction by these inflammatory cells, and attempts at repair through fibrosis and new blood vessel formation.
Principles of cell injury and cellular adaptation .pptMirza Anwar Baig
This document provides an overview of cell injury and adaptation. It discusses various causes of cell injury including hypoxia, infections, physical and chemical agents. The pathogenesis and morphology of reversible and irreversible cell injury is explained. Cellular adaptations such as atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia are defined. Necrosis and apoptosis are compared as two types of cell death. Specific examples of cell injuries and adaptations in different organ systems are also presented.
Fatty change, also known as steatosis, is the abnormal accumulation of triglycerides within parenchymal cells. The most common location is the liver, as it is responsible for fat metabolism. Fatty change can be caused by toxins, alcohol abuse, protein malnutrition, diabetes mellitus, obesity, or anoxia. Alcohol abuse and diabetes associated with obesity are the most common causes of fatty liver. In diabetes, insulin resistance results in triglyceride accumulation in liver cells through impaired fatty acid oxidation, increased fatty acid synthesis and uptake, and decreased secretion of VLDL from the liver. Fat-laden liver cells are sensitive to oxidative stress damage from free radicals, which can cause mitochondrial and cell membrane
Hyperplasia is an increase in the number of cells in an organ due to increased cell proliferation. There are two types of hyperplasia: physiological and pathological. Physiological hyperplasia occurs normally, such as the growth of breast tissue during puberty and pregnancy or the compensatory growth of liver cells after partial resection. Pathological hyperplasia is caused by excessive hormones or growth factors and can lead to conditions like endometrial hyperplasia or benign prostatic hyperplasia. The hyperplastic process remains controlled and will disappear if the initiating signals subside.
This document discusses chronic inflammation. It describes chronic inflammation as inflammation of prolonged duration involving ongoing inflammation, tissue injury, and attempts at repair. Chronic inflammation is characterized by mononuclear cell infiltration, tissue destruction, and attempts at healing through fibrosis and angiogenesis. Macrophages are a key player in chronic inflammation by secreting cytokines, growth factors, enzymes, and other inflammatory mediators that can cause both inflammatory tissue injury and repair. Granulomatous inflammation is a distinctive pattern of chronic inflammation seen in some infectious and noninfectious conditions, where macrophages form aggregates surrounded by lymphocytes called granulomas in an attempt to control difficult to eradicate agents.
The document summarizes the process of hemostasis (prevention of blood loss after injury) which involves vascular constriction, platelet plug formation, and coagulation. It describes the roles of platelets, coagulation factors, fibrinolysis, and endothelial cells in hemostasis and thrombosis. Abnormalities that can cause bleeding disorders or thrombosis are also listed.
Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis.
Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.
Cell injury and Cellular Adaptation: PathologyHarshit Jadav
This document discusses various types of cell injury, including reversible and irreversible injury. It outlines several causes of cell injury, such as hypoxia, physical agents, chemicals/drugs, microbial agents, immunologic agents, and nutritional derangements. The document also discusses various cellular adaptations that cells undergo in response to stress, including atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia. Overall, the document provides an overview of the different forms of cell injury, causes of injury, and adaptive cellular responses.
This document provides an overview of amyloidosis, including:
- Amyloidosis is characterized by extracellular deposition of misfolded proteins that form insoluble fibrils, damaging tissues.
- There are different types classified by the misfolded protein involved, including AL, AA, and rare forms.
- Organs commonly affected include the kidney, heart, GI tract, and nerves.
- Diagnosis involves biopsy of affected tissues and staining with Congo red to identify amyloid deposits.
- Prognosis depends on type and organ involvement, with generalized amyloidosis having a poor prognosis of around 2 years.
Basics of hyperlipoproreinemia in an easy and understandable way.gives a brief picture of the disease , it's cauusitive agents and clinical sequelae following it.
This document discusses environmental and nutritional pathology. It covers common exposures like outdoor air pollution, medications, tobacco, and alcohol. Tobacco is a major cause of preventable death, linked to cancers of the lung, esophagus, and other organs. Alcohol abuse can cause fatty liver, hepatitis, cirrhosis, and neurological issues due to thiamine deficiency. Medications like oral contraceptives and hormone replacement therapy may increase risks of blood clots and some cancers. Occupational diseases frequently involve repeated trauma or toxic exposures affecting the lungs and skin.
Necrosis is the death of cells and living tissue. It is caused by factors such as hypoxia, toxins, or trauma. There are several types of necrosis that are distinguished by their appearance and tissue effects. Coagulative necrosis involves cell death while maintaining tissue structure. Liquefactive necrosis completely digests dead cells. Caseous necrosis, seen in tuberculosis, has a cheese-like appearance.
Recent Human Anatomy: Regional and Clinical in three volumes is based on the Anatomy syllabus for MBBS-I course in India, as per the recommendation of the Medical Council of India (MCI) and All India Institute of Medical Sciences (AIIMS). It covers the entire range of prescribed topics in General Anatomy, Gross Anatomy, Embryology, Histology, Neuroanatomy, and Clinical Anatomy.
Features
• About 500 MCQs in each volume (with answers) to help prepare for objective tests, including NEET
• Over 500 clear, full-colour illustrations
• Comprehensive treatment of Clinical Anatomy, including clinical importance of Anatomy, clinical methods to examine a patient, and surgical procedures, to prepare students for further clinical studies
• Complete yet concise descriptions in Gross Anatomy with the use of tables
• Presentation of Histology of organs and their Histophysiology with illustrated diagrams
• Histology of tubular organs described from the inner to the outer side, for better comprehension
• An efficient approach to the study of Neuroanatomy, top downwards
This document provides an overview of the PATH 201 General Pathology course. It includes the course contents which cover topics like cell injury, growth disturbances, inflammation, and neoplasia. Recommended textbooks are listed. The document also defines pathology as the study of derangements in living organisms in response to injuries. It briefly outlines some career paths in veterinary pathology and discusses the history of pathology from ancient concepts to modern developments in anatomy, microscopy, germ theory, and molecular biology.
Pathology is the scientific study of disease through examination of organs, tissues, bodily fluids, and sometimes whole bodies. It involves studying the structural and functional changes caused by disease. Pathologists examine samples through various methods including gross examination, histopathology, immunohistochemistry, and electron microscopy to diagnose disease and understand disease processes and causes. The main subdivisions of pathology are anatomical pathology, clinical pathology, forensic pathology, and neuropathology.
Healing occurs through regeneration or scar formation depending on the cell and injury type. Wound healing follows two main pathways: primary intention for clean surgical wounds where edges are approximated, or secondary intention for wounds with separated edges and more tissue death. The process involves inflammation, granulation tissue formation, re-epithelialization, wound contraction and ECM deposition. Several local and systemic factors can delay healing including infection, poor blood supply, drugs, and nutritional deficiencies.
This document discusses cell injury and cell death. It defines cell injury as a change in cell structure, metabolism or function that impairs its vital activity. Causes of cell injury include internal stresses like metabolic imbalances and external stresses such as physical agents, toxins, and chemicals. Cell injury can be reversible or irreversible and lead to cell death through mechanisms like necrosis, autolysis, or apoptosis. Signs of cell injury include morphological changes, functional impairments, and metabolic derangements. Specific types of cell injury discussed include fatty change, pigmentation, calcification, amyloidosis, and various forms of necrosis.
Cells can adapt to changes in their environment through various processes including hyperplasia, hypertrophy, atrophy, metaplasia, and dysplasia. Hyperplasia is an increase in cell number, hypertrophy is an increase in cell size, and atrophy is a decrease in cell size or number. Metaplasia is a reversible change where one adult cell type replaces another. Dysplasia involves disordered cellular development and proliferation with cytological abnormalities. These adaptations allow cells to survive stresses and ensure tissue homeostasis.
This document discusses different types of cell death known as necrosis. It defines necrosis as irreversible damage to cells that cannot be corrected and involves failure of ATP generation, membrane damage, and damage from reactive oxygen species. The document outlines several patterns of necrosis including coagulative necrosis where tissue architecture is preserved, liquefactive necrosis where tissue turns into a viscous liquid, and caseous necrosis where tissue has a cheesy, yellow-white appearance. It also discusses specific forms of necrosis that can occur in conditions like infections, gangrene, acute pancreatitis, and immune reactions.
Pathological calcification involves the abnormal deposition of calcium salts in tissues other than bone. There are two main types: dystrophic calcification occurs in dead or damaged tissue with normal calcium levels, while metastatic calcification affects normal tissues and results from disorders that increase calcium levels in the blood (hypercalcemia). Dystrophic calcification is seen in areas of necrosis, atherosclerotic plaques, and infarcts. Metastatic calcification commonly involves the kidneys, lungs, blood vessels, and stomach, and is caused by hyperparathyroidism, bone destruction, or excessive vitamin D intake.
This document defines inflammation and describes the key cellular and vascular events involved. Inflammation is the body's response to injury or infection, and involves vascular changes such as increased blood flow and permeability, as well as cellular events like the migration of white blood cells. These events are mediated by chemical signaling molecules called mediators, which help regulate the inflammatory response. The document outlines the major mediators involved and their roles in vascular changes, cellular recruitment, and resolution of inflammation.
This document summarizes different types of reversible cell injury seen microscopically, including hydropic change, hyaline change, mucoid change, and fatty change. Hydropic change is characterized by cytoplasmic vacuolation and swelling of cells. Hyaline change results in a glassy, eosinophilic appearance of intracellular or extracellular proteins. Mucoid change describes excess intracellular or extracellular mucin accumulation. Fatty change or steatosis involves intracellular accumulation of neutral fats within cells. Each type of change is described in detail with examples and microscopic images.
1) Chronic inflammation is inflammation of prolonged duration that can occur following acute inflammation or persistently as active inflammation, often resulting in tissue destruction and repair processes.
2) Causes of chronic inflammation include persistent infections, prolonged exposure to toxic agents, and autoimmunity.
3) Morphological features of chronic inflammation are characterized by infiltration of mononuclear cells like macrophages and lymphocytes, tissue destruction by these inflammatory cells, and attempts at repair through fibrosis and new blood vessel formation.
Principles of cell injury and cellular adaptation .pptMirza Anwar Baig
This document provides an overview of cell injury and adaptation. It discusses various causes of cell injury including hypoxia, infections, physical and chemical agents. The pathogenesis and morphology of reversible and irreversible cell injury is explained. Cellular adaptations such as atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia are defined. Necrosis and apoptosis are compared as two types of cell death. Specific examples of cell injuries and adaptations in different organ systems are also presented.
Fatty change, also known as steatosis, is the abnormal accumulation of triglycerides within parenchymal cells. The most common location is the liver, as it is responsible for fat metabolism. Fatty change can be caused by toxins, alcohol abuse, protein malnutrition, diabetes mellitus, obesity, or anoxia. Alcohol abuse and diabetes associated with obesity are the most common causes of fatty liver. In diabetes, insulin resistance results in triglyceride accumulation in liver cells through impaired fatty acid oxidation, increased fatty acid synthesis and uptake, and decreased secretion of VLDL from the liver. Fat-laden liver cells are sensitive to oxidative stress damage from free radicals, which can cause mitochondrial and cell membrane
Hyperplasia is an increase in the number of cells in an organ due to increased cell proliferation. There are two types of hyperplasia: physiological and pathological. Physiological hyperplasia occurs normally, such as the growth of breast tissue during puberty and pregnancy or the compensatory growth of liver cells after partial resection. Pathological hyperplasia is caused by excessive hormones or growth factors and can lead to conditions like endometrial hyperplasia or benign prostatic hyperplasia. The hyperplastic process remains controlled and will disappear if the initiating signals subside.
This document discusses chronic inflammation. It describes chronic inflammation as inflammation of prolonged duration involving ongoing inflammation, tissue injury, and attempts at repair. Chronic inflammation is characterized by mononuclear cell infiltration, tissue destruction, and attempts at healing through fibrosis and angiogenesis. Macrophages are a key player in chronic inflammation by secreting cytokines, growth factors, enzymes, and other inflammatory mediators that can cause both inflammatory tissue injury and repair. Granulomatous inflammation is a distinctive pattern of chronic inflammation seen in some infectious and noninfectious conditions, where macrophages form aggregates surrounded by lymphocytes called granulomas in an attempt to control difficult to eradicate agents.
The document summarizes the process of hemostasis (prevention of blood loss after injury) which involves vascular constriction, platelet plug formation, and coagulation. It describes the roles of platelets, coagulation factors, fibrinolysis, and endothelial cells in hemostasis and thrombosis. Abnormalities that can cause bleeding disorders or thrombosis are also listed.
Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis.
Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.
Cell injury and Cellular Adaptation: PathologyHarshit Jadav
This document discusses various types of cell injury, including reversible and irreversible injury. It outlines several causes of cell injury, such as hypoxia, physical agents, chemicals/drugs, microbial agents, immunologic agents, and nutritional derangements. The document also discusses various cellular adaptations that cells undergo in response to stress, including atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia. Overall, the document provides an overview of the different forms of cell injury, causes of injury, and adaptive cellular responses.
This document provides an overview of amyloidosis, including:
- Amyloidosis is characterized by extracellular deposition of misfolded proteins that form insoluble fibrils, damaging tissues.
- There are different types classified by the misfolded protein involved, including AL, AA, and rare forms.
- Organs commonly affected include the kidney, heart, GI tract, and nerves.
- Diagnosis involves biopsy of affected tissues and staining with Congo red to identify amyloid deposits.
- Prognosis depends on type and organ involvement, with generalized amyloidosis having a poor prognosis of around 2 years.
Basics of hyperlipoproreinemia in an easy and understandable way.gives a brief picture of the disease , it's cauusitive agents and clinical sequelae following it.
This document discusses environmental and nutritional pathology. It covers common exposures like outdoor air pollution, medications, tobacco, and alcohol. Tobacco is a major cause of preventable death, linked to cancers of the lung, esophagus, and other organs. Alcohol abuse can cause fatty liver, hepatitis, cirrhosis, and neurological issues due to thiamine deficiency. Medications like oral contraceptives and hormone replacement therapy may increase risks of blood clots and some cancers. Occupational diseases frequently involve repeated trauma or toxic exposures affecting the lungs and skin.
Necrosis is the death of cells and living tissue. It is caused by factors such as hypoxia, toxins, or trauma. There are several types of necrosis that are distinguished by their appearance and tissue effects. Coagulative necrosis involves cell death while maintaining tissue structure. Liquefactive necrosis completely digests dead cells. Caseous necrosis, seen in tuberculosis, has a cheese-like appearance.
Recent Human Anatomy: Regional and Clinical in three volumes is based on the Anatomy syllabus for MBBS-I course in India, as per the recommendation of the Medical Council of India (MCI) and All India Institute of Medical Sciences (AIIMS). It covers the entire range of prescribed topics in General Anatomy, Gross Anatomy, Embryology, Histology, Neuroanatomy, and Clinical Anatomy.
Features
• About 500 MCQs in each volume (with answers) to help prepare for objective tests, including NEET
• Over 500 clear, full-colour illustrations
• Comprehensive treatment of Clinical Anatomy, including clinical importance of Anatomy, clinical methods to examine a patient, and surgical procedures, to prepare students for further clinical studies
• Complete yet concise descriptions in Gross Anatomy with the use of tables
• Presentation of Histology of organs and their Histophysiology with illustrated diagrams
• Histology of tubular organs described from the inner to the outer side, for better comprehension
• An efficient approach to the study of Neuroanatomy, top downwards
This document provides an overview of the PATH 201 General Pathology course. It includes the course contents which cover topics like cell injury, growth disturbances, inflammation, and neoplasia. Recommended textbooks are listed. The document also defines pathology as the study of derangements in living organisms in response to injuries. It briefly outlines some career paths in veterinary pathology and discusses the history of pathology from ancient concepts to modern developments in anatomy, microscopy, germ theory, and molecular biology.
Introduction to human anatomy for ms studentDiribaErko
This document provides an overview of the history of anatomy from ancient times to modern day. It discusses early Greek physicians like Hippocrates and Aristotle and their contributions. During the Renaissance period, scientists like Leonardo da Vinci and Andreas Vesalius made significant advances through human dissection. Major developments continued into the 19th century with discoveries like the cell, genetics, and X-rays. The document also defines key anatomical terminology and describes the regional, clinical, and systemic approaches to studying human anatomy.
This document provides an introduction to histopathology. It discusses that histopathology is the branch of pathology that deals with tissue changes associated with disease, using microscopic examination of biopsy specimens. It also provides background on pathology, noting that pathology involves the study of structural and functional changes in tissues that cause disease. Several pioneers in the fields of anatomy, microscopy, and cellular pathology are discussed, including Hippocrates, Aristotle, Van Leeuwenhoek, Morgagni, Bichat, and Virchow. Basic terminology used in pathology is defined.
Veterinary medicine was separated from human medicine in 1761 with the founding of the first veterinary school in Lyon, France. Before this, doctors treated both humans and animals. The modern era of biomedical research began in the late 18th century with discoveries like Edward Jenner's smallpox vaccine and Robert Koch's findings about bacteria transmission. Key early scientists who studied cells under microscopes in the 1600s-1800s helped develop the cell theory. In the post-18th century period, many important researchers from various countries made contributions to medicine. As science and technology advanced, medicine became more reliant on medications and pharmacology while adopting evidence-based practices.
The document provides an overview of various subjects and topics in basic medical science. It includes sections on anatomy, embryology, biochemistry, histology, epidemiology, biostatistics, molecular biology, genetics, cell biology, endocrinology, general pathology, immunology, microbiology, physiology, pathophysiology, pathology, pathogenesis, neuroscience, pharmacology, toxicology, medicine, medical history and other related topics. Each section provides definitions and background information on the topic.
Modern biology is a broad field composed of many interconnected subdisciplines that study life at different scales. While diverse, biology is unified by some key concepts like evolution, cells as the basic unit of life, and genes as the basic unit of heredity. Subdisciplines include biochemistry, molecular biology, botany, cellular biology, physiology, ecology, and evolutionary biology. Biology has developed significantly since ancient times, with major advances in microscopy revealing cells and advances in genetics revealing DNA as the carrier of heredity. The modern synthesis of Darwin's theory of evolution by natural selection with genetics and population genetics formed the foundation of modern biology.
Anatomy is the study of the structures of living organisms. The field began with early Greeks who first performed dissections to understand the human body. Over time, anatomists used improved tools like microscopes and staining techniques to study smaller structures from the cellular level onward. A key figure was Andreas Vesalius in the 16th century, whose work overturned Galen's anatomical theories and established anatomy on a basis of direct observation. Modern anatomy relies on tools like electron microscopes and molecular techniques to examine subcellular and molecular structures. Comparative anatomy also compares structures across species to understand evolutionary changes.
The document provides a history of the Physiology Department at Cairo University's Faculty of Veterinary Medicine. It traces the department back to its establishment in the early 20th century when the first veterinary school was opened in Egypt. It details the early leadership of the department and contributions of pioneering professors. It also outlines the department's growth over the decades as it took on more staff, expanded its research activities, and became more specialized in different areas of physiology. The history shows how the department has played a key role in developing the field of veterinary physiology in Egypt.
The Nobel Prize is awarded annually for achievements in physics, chemistry, physiology or medicine, literature, and peace. The prizes were first awarded in 1901 in accordance with Alfred Nobel's will. The 1901 prizes in physiology or medicine were awarded to Emil von Behring for his work on diphtheria antitoxin and Paul Ehrlich for his work on immunity and chemotherapy. Subsequent prizes have been awarded for major advances in understanding the immune system, including discoveries of monoclonal antibodies, the major histocompatibility complex, immune tolerance, and the roles of dendritic cells and innate immunity.
This document provides an overview of the history and relevance of microbiology. It discusses how microbiology is the study of microorganisms that cannot be seen with the naked eye. It outlines the diversity of microorganisms and their ubiquitous nature. The document also describes the development of the field from early theories of disease to the acceptance of germ theory in the late 19th century. This included the development of tools like microscopes and experiments that disproved spontaneous generation. The impact of microorganisms on human health and ecosystems is also summarized.
This document provides an introduction to chemotherapy. It discusses the history of chemotherapy from ancient uses of medicinal plants to treat infections to major discoveries of antibiotics in the 20th century. These include Fleming's discovery of penicillin, Waksman's discovery of streptomycin, and the mass production of penicillin during World War II. The document defines key terms related to infectious diseases and chemotherapy and outlines principles of antimicrobial therapy including mechanisms of selective targeting, therapeutic index, identification of infecting organisms, and empiric therapy prior to identification.
This biotech slideshare explain about Pathology. Different kinds of pathology. Different instruments used in detection of of any pathology related diseases like Sonography and X-ray.
The document provides a history of veterinary pathology, beginning with early evidence of disease in ancient human remains. As civilization developed and domestication of animals increased, comparative pathology using animal dissection helped improve understanding of human anatomy and disease. Important early figures included Heterphilos, Erasistratos, and Virchow, whose work at abattoirs advanced meat inspection and disease study. The 1800s saw calls for standardized necropsy procedures and disease descriptions. Veterinary pathology lagged behind human pathology until the 1940s, when training programs grew in North America and Europe, advancing the field.
The integumentary system consists of the skin, hair, nails, and glands. The skin is composed of three layers - the epidermis, dermis, and subcutaneous tissue. The epidermis is made of stratified squamous epithelium and provides a protective barrier. Below the epidermis lies the dermis, a vascular connective tissue layer. Below the dermis is the subcutaneous tissue. Skin appendages include hair, nails, and glands that secrete substances like sebum. The integumentary system functions to regulate body temperature, prevent fluid loss, provide immune protection, produce vitamin D, and allow for sensation.
The document summarizes the bones that make up the axial and appendicular skeleton in humans. The axial skeleton consists of 80 bones including the skull, vertebral column, rib cage, and hyoid bone. The appendicular skeleton contains 126 bones and includes the shoulder girdle, upper limbs, pelvic girdle, and lower limbs. Key bones of the appendicular skeleton are the humerus, radius, ulna, carpals, metacarpals, phalanges, femur, tibia, fibula, tarsals, metatarsals and phalanges.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help boost feelings of calmness, happiness and focus.
The document discusses the mechanisms that regulate blood pressure in the short term, including the nervous system and chemicals. It explains that the nervous system, including the baroreceptor reflex and chemoreceptors, controls blood pressure by changing peripheral resistance within seconds or minutes in response to changes in blood pressure. The document also outlines the roles of the vasomotor center, sympathetic and parasympathetic activity, and adrenal glands in short term blood pressure regulation.
The document discusses the vascular system and blood vessels. It describes the three layers of blood vessels - tunica intima, tunica media, and tunica externa. It also explains the double circulation system, with the pulmonary circuit pumping blood to the lungs and the systemic circuit pumping blood to the body's systems. The systemic system can be divided into the coronary, renal, and hepatic portal circulations.
The document discusses the benefits of meditation for reducing stress and anxiety. Regular meditation practice can help calm the mind and body by lowering heart rate and blood pressure. Making meditation a part of a daily routine, even if just 10-15 minutes per day, can offer improvements to mood, focus, and overall feelings of well-being over time.
Cells communicate with each other through chemical and mechanical signals. In multicellular organisms, cell signaling allows cells to specialize and coordinate their functions from distant organs. Cells communicate through chemical messengers like hormones and neurotransmitters that act as signals between cells. Cell communication guides processes like development, homeostasis, and cell migration. There are several types of cell signaling including endocrine, paracrine, autocrine, and direct cell junctions through gap junctions and desmosomes. Contact inhibition is a process where normal cell growth stops upon contact with other cells.
This document summarizes key aspects of lipid metabolism and hyperlipidemia management. It defines lipids and lipoproteins, describes their normal roles and abnormalities. Mechanisms and examples of different drug classes for treating hyperlipidemia are provided, including statins, fibrates, bile acid sequestrants, nicotinic acid, ezetimibe, and PCSK9 inhibitors. Their mechanisms, therapeutic uses, side effects and drug interactions are concisely outlined. Non-drug management including lifestyle changes and therapeutic lifestyle counseling are also mentioned.
Parkinsonism is a chronic neurodegenerative disease typically affecting men over age 50, characterized by shaking, rigidity, and difficulty with motor control and movement. Common drugs used to treat Parkinsonism symptoms include L-Dopa combined with Carbidopa to increase dopamine levels; dopamine agonists like Pergolide and Bromocriptine which activate dopamine receptors; MAO-B inhibitors like Selegiline; and anticholinergic agents such as Benzhexol that reduce muscle stiffness and tremors.
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The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
Introduction and scope of anatomy and physiologyJaineel Dharod
This document provides an introduction to human anatomy and physiology. It defines anatomy as the study of body structures and physiology as the study of body functions. It describes the levels of structural organization from chemical to cellular to tissue to organ to system to organism. Key body systems include the digestive and circulatory systems. Basic life processes that distinguish living things from non-living things are also outlined, including metabolism, responsiveness, movement, growth, differentiation, and reproduction. Homeostasis and the body's feedback systems that maintain stable internal conditions are then discussed.
- Toxicology is the scientific study of adverse effects of chemicals on living organisms. It involves observing and reporting symptoms, mechanisms, detection and treatments of toxic substances in relation to human poisoning.
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This document provides an overview of anatomy and physiology. It defines anatomy as the study of body structures and their relationships, and physiology as the study of body functions. It discusses the basic life processes like metabolism, responsiveness, movement, growth, differentiation, and reproduction. It also introduces homeostasis as the body's process of maintaining equilibrium, and describes the different body fluids, including intracellular fluid, extracellular fluid, interstitial fluid, blood plasma, lymph, cerebrospinal fluid, synovial fluid, and fluids of the eye. Key anatomical and directional terminology is also covered.
Oxidized low-density lipoproteins induce endothelial cell activation and expression of adhesion molecules, leading to monocyte adhesion and transmigration into the intima where they become macrophages. Macrophages incorporate modified lipoproteins and become foam cells, while an inflammatory response causes smooth muscle cell migration and replication in the plaque. Macrophages in the plaque have abnormal lipid metabolism and reduced cholesterol efflux, accumulating apoptotic and necrotic debris to form a necrotic core.
Chronic inflammation can be classified into two main types: chronic non-specific inflammation characterized by non-specific cell infiltration, and chronic granulomatous inflammation characterized by the formation of granulomas. Granulomas are circumscribed inflammatory lesions composed predominantly of aggregated macrophages called epithelioid cells rimmed by lymphocytes. Granulomas form via a process involving macrophage engulfment of pathogens, recruitment of CD4+ T cells, and cytokine signaling. The typical structural composition of a granuloma includes epithelioid cells, multinucleate giant cells formed by epithelioid cell fusion, lymphocytes, central necrosis in some conditions, and peripheral fibrosis during healing. Diseases that form granulomas include tuberculosis
This document discusses receptor occupancy theory and dose-response curves. It explains that receptor occupancy theory is based on the law of mass action, where response comes from a drug occupying a receptor. A dose-response curve shows the observed effect of a drug as a function of its concentration in the receptor compartment. The curve reaches an asymptotic maximum when all receptor sites are occupied. The drug-receptor interaction is characterized by drug binding to the receptor, followed by a response in the biological system. The affinity of drug binding is governed by chemical forces that cause reversible association with the receptor. This relationship depends on the forward association rate and reverse dissociation rate. At equilibrium, the dissociation constant is the ratio of the off-rate and on
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Are you looking for a long-lasting solution to your missing tooth?
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8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
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Cell injury; complete chapter
1. 1 Cell Injury - Pathophysiology
• Explanation of Pathophysiology:
The word ‘Pathology’ is derived from two Greek words—pathos meaning suffering, and logos meaning
study. Pathology is, thus, scientific study of structure and function of the body in disease; or in other
words, pathology consists of the abnormalities that occur in normal anatomy (including histology) and
physiology owing to disease.
Another commonly used term with reference to study of diseases is ‘pathophysiology’ comprised by two
words: pathos = suffering; physiology = study of normal function. Pathophysiology, thus, includes study
of disordered function or breakdown of homeostasis in diseases. Pathologists are the diagnosticians of
disease.
• Health & Disease:
Health may be defined as a condition when the individual is in complete accord with the surroundings,
while disease is loss of ease (or comfort) to the body (i.e. dis-ease).
• Difference between Disease, illness & Syndrome:
A term commonly confused with disease is illness. While disease suggests an entity with a cause, illness is
the reaction of the individual to disease in the form of symptoms (complaints of the patient) and physical
signs (elicited by the clinician). Though disease and illness are not separable, the study of diseases is done
in pathology while the learning and management of illnesses is done in wards and clinics.
In addition to disease and illness, there are syndromes (meaning running together) characterized by
combination of symptoms caused by altered physiologic processes.
• Common Terminologies a Healthcare professional should be aware of:
Patient is the person affected by disease.
Lesions are the characteristic changes in tissues and cells produced by disease in an individual or
experimental animal.
Pathologic changes or morphology consist of examination of diseased tissues.
Pathologic changes can be recognized with the naked eye (gross or macroscopic changes) or studied by
microscopic examination of tissues.
Causal factors responsible for the lesions are included in etiology of disease (i.e. ‘why’ of disease).
Mechanism by which the lesions are produced is termed pathogenesis of disease (i.e. ‘how’ of disease).
Functional implications of the lesion felt by the patient are symptoms and those discovered by the
clinician are the physical signs.
Clinical significance of the morphologic and functional changes together with results of other
investigations help to arrive at an answer to what is wrong (diagnosis), what is going to happen
(prognosis), what can be done about it (treatment), and finally what should be done to avoid
complications and spread (prevention) (i.e. ‘what’ of disease).
2. 2 Cell Injury - Pathophysiology
History of Pathophysiology:
PRE-Historic ERA (till 1500 AD):
Hippocrates introduced ethical concepts in the practice of medicine and is revered by the medical
profession by taking ‘Hippocratic oath’ at the time of entry into practice of medicine.
Hippocratic teaching was propagated in Rome by Roman physicians, notably by Cornelius Celsus (53 BC-7
AD) and Cladius Galen (130–200 AD). Celsus first described four cardinal signs of inflammation—rubor
(redness), tumor (swelling), calor (heat), and dolor (pain).
Galen postulated humoral theory, later called Galenic theory. This theory suggested that the illness
resulted from imbalance between four humors (or body fluids): blood, lymph, black bile (believed to be
from the spleen), and biliary secretion from the liver.
The hypothesis of disequilibrium of four elements constituting the body (Dhatus) similar to Hippocratic
doctrine finds mention in ancient Indian medicine books compiled about 200 AD—Charaka Samhita, a
finest document by Charaka on medicine listing 500 remedies, and Sushruta Samhita, similar book of
surgical sciences by Sushruta, and includes about 700 plant-derived medicines.
ERA of Gross Pathology (1500 – 1800 AD):
The beginning of the development of human anatomy took place during this period with the art works
and drawings of human muscles and embryos by famous Italian painter Leonardo da Vinci (1452–1519).
Dissection of human body was started by Vesalius (1514–1564) on executed criminals. His pupils, Gabriel
Fallopius, (1523–1562) who described human oviducts (Fallopian tubes) and Fabricius, who discovered
lymphoid tissue around the intestine of birds (bursa of Fabricius) further popularized the practice of
human anatomic dissection for which special postmortem amphitheaters came in to existence in various
parts of ancient Europe.
Richard Bright (1789–1858) who described nonsuppurative nephritis, later termed glomerulonephritis or
Bright’s disease; Thomas Addison (1793–1860) who gave an account of chronic adrenocortical
insufficiency termed Addison’s disease; and Thomas Hodgkin (1798–1866), who observed the complex of
chronic enlargement of lymph nodes, often with enlargement of the liver and spleen, later called
Hodgkin’s disease.
Towards the end of 18th century, Xavier Bichat (1771–1802) in France described that organs were
composed of tissue and divided the study of morbid anatomy into General Pathology and Systemic
Pathology. R.T.H. Laennec (1781–1826), another French physician, dominated the early part of 19th
century by his numerous discoveries. He described several lung diseases (tubercles, caseous lesions,
miliary lesions, pleural effusion, bronchiectasis), chronic sclerotic liver disease (later called Laennec’s
cirrhosis) and invented stethoscope.
ERA of Technological Development in pathology (1800 – 1950):
Sophistication in surgery led to advancement in pathology. The anatomist-surgeons of earlier centuries
got replaced largely with surgeon-pathologists in the 19th century. Pathology started developing as a
diagnostic discipline in later half of the 19th century with the evolution of cellular pathology which was
3. 3 Cell Injury - Pathophysiology
closely linked to technology advancements in machinery manufacture for cutting thin sections of tissue,
improvement in microscope, and development of chemical industry and dyes for staining.
The discovery of existence of disease-causing microorganisms was made by French chemist Louis Pasteur
(1822–1895), thus demolishing the prevailing theory of spontaneous generation of disease and firmly
established germ theory of disease. Subsequently, G.H.A. Hansen (1841–1912) in Germany identified
Hansen’s bacillus as causative agent for leprosy (Hansen’s disease) in 1873. While the study of infectious
diseases was being made, the concept of immune tolerance and allergy emerged which formed the basis
of immunisation initiated by Edward Jenner.
Paul Ehrlich (1854–1915), German physician, conferred Nobel prize in 1908 for his work in immunology,
described Ehrlich’s test for urobilinogen using Ehrlich’s aldehyde reagent, staining techniques of cells and
bacteria, and laid the foundations of clinical pathology (Fig. 1.5).
Christian Gram (1853–1938), Danish physician, who developed bacteriologic staining by crystal violet.
D.L. Romanowsky (1861–1921), Russian physician, who developed stain for peripheral blood film using
eosin and methylene blue derivatives.
Robert Koch (1843–1910), German bacteriologist who, besides Koch’s postulate and Koch’s phenomena,
developed techniques of fixation and staining for identification of bacteria, discovered tubercle bacilli in
1882 and cholera vibrio organism in 1883.
Sir William Leishman (1865–1926) who described Leishman’s stain for blood films in 1914 and observed
Leishman-Donovan bodies (LD bodies) in leishmaniasis.
Robert Feulgen (1884–1955) who described Feulgen reaction for DNA staining and laid the foundations
of cytochemistry and histochemistry.
Karl Landsteiner (1863–1943) described the existence of major human blood groups in 1900 and was
awarded Nobel prize in 1930 and is considered father of blood transfusion.
Modern Pathology (Post 1950):
21st
century have made it possible to study diseases at molecular level. The major impact of advances in
molecular biology are in the field of diagnosis and treatment of genetic disorders, immunology and in
cancer. Some of the revolutionary discoveries during this time are as under;
• Description of the structure of DNA of the cell by Watson and Crick in 1953.
• Identification of chromosomes and their correct number in humans (46) by Tijo and Levan in 1956.
• Identification of Philadelphia chromosome t (9;22) in chronic myeloid leukemia by Nowell and
Hagerford in 1960 as the first chromosomal abnormality in any cancer.
• In Situ Hybridization introduced in 1969 in which a labelled probe is employed to detect and
localize specific RNA or DNA sequences ‘in situ’ (i.e. in the original place).
• Recombinant DNA technique developed in 1972 using restriction enzymes to cut and paste bits of
DNA.
• In 1983, Kary Mullis introduced polymerase chain reaction (PCR) i.e. “xeroxing” DNA fragments
which revolutionized the diagnostic molecular genetics.
4. 4 Cell Injury - Pathophysiology
• In 1997, Ian Wilmut and his colleagues at Roslin Institute in Edinburgh, successfully used a
technique of somatic cell nuclear transfer to create the clone of a sheep; the cloned sheep was
named Dolly. This has set in the era of mammalian cloning.
• In April 2003, Human Genome Project (HGP) consisting of a consortium of countries, was
completed which coincided with 50 years of description of DNA double helix by Watson and Crick
in April 1953. The sequencing of human genome reveals that human genome contains
approximately 3 billion of the base pairs, which reside in the 23 pairs of chromosomes within the
nucleus of all human cells. Each chromosome contains an estimated 30,000 genes in the human
genome, which carry the instructions for making proteins. The HGP gave us the ability to read
nature’s complete genetic blueprint for building each human being. All this has opened new ways
in treating and researching an endless list of diseases that are currently incurable.
5. 5 Cell Injury - Pathophysiology
CELL INJURY AND CELLULAR ADAPTATIONS
Cells are the basic units of tissues, which form organs and systems in the human body. In 1859,
Virchow first published cellular theory of disease, bringing in the concept that diseases occur due
to abnormalities at the level of cells. Since then, study of abnormalities in structure and function
of cells in disease has remained the focus of attention in understanding of diseases. Thus, most
forms of diseases begin with cell injury followed by consequent loss of cellular function. Cell injury
is defined as a variety of stresses a cell encounters as a result of changes in its internal and external
environment.
In general, cells of the body have inbuilt mechanism to deal with changes in environment to an
extent. The cellular response to stress may vary and depends upon the following variables:
a) The type of cell and tissue involved.
b) Extent and type of cell injury.
Various forms of cellular responses to cell injury may be as follows:
Figure 1: Cellular Adaptation under Stress
A. When there is increased functional demand, the cell may adapt to the changes which are
expressed morphologically and then revert back to normal after the stress is removed
(cellular adaptations)
B. When the stress is mild to moderate, the injured cell may recover (reversible cell injury),
while when the injury is persistent cell death may occur (irreversible cell injury).
C. The residual effects of reversible cell injury may persist in the cell as evidence of cell injury
at subcellular level (subcellular changes), or metabolites may accumulate within the cell
(intracellular accumulations).
6. 6 Cell Injury - Pathophysiology
THE NORMAL CELL
Different types of cells of the body possess features which distinguish one type from another. However,
most mammalian cells have a basic plan of common structure and function, except the red blood cell
which is devoid of nucleus.
The Principle components of a cell are: Cell Membrane, Nucleus, Nucleolus, Endoplasmic Reticulum
(Smooth/Rough), Ribosome (protein factory), Mitochondria (Powerhouse), Vacuole (packaging center of
proteins), Golgi Complex, Cytoplasm, Centrioles, etc.
Figure 2: Principle components of a cell
• Nucleus: The Centre of cell with genetic information
• Nucleosome: Condensed chromosomes and DNA
• Rough Endoplasmic Reticulum & Smooth Endoplasmic Reticulum: Sites for protein
synthesis and packaging
• Ribosomes: Protein Factory (translation site)
• Golgi body & Lysosomes: The packaging unit
• Mitochondria: The powerhouse of the cell (Produces ATP)
• Centrioles: Transporters of cell organelles during cell division
7. 7 Cell Injury - Pathophysiology
ETIOLOGY OF CELL INJURY
The cells may be broadly injured by two major ways:
A. By genetic causes
B. By acquired causes
Based on underlying agent, the acquired causes of cell injury can be further categorized as under:
1. Hypoxia and ischemia
2. Physical agents
3. Chemical agents and drugs
4. Microbial agents
5. Immunologic agents
6. Nutritional derangements
7. Aging
8. Psychogenic diseases
9. Iatrogenic factors
10. Idiopathic diseases
1. HYPOXIA AND ISCHAEMIA
Cells of different tissues essentially require oxygen to generate energy and perform metabolic functions.
Deficiency of oxygen or hypoxia results in failure to carry out these activities by the cells. Hypoxia is the
most common cause of cell injury. Hypoxia may result from the following:
✓ The most common mechanism of hypoxic cell injury is by reduced supply of blood to cells due to
interruption i.e. ischemia.
✓ However, hypoxia may result from other causes as well e.g. disorders of oxygen-carrying RBCs
(e.g. anemia, carbon monoxide poisoning), heart diseases, lung diseases and increased demand
of tissues.
2. PHYSICAL AGENTS
Physical agents in causation of disease are as under:
✓ mechanical trauma (e.g. road accidents);
✓ thermal trauma (e.g. by heat and cold);
✓ electricity;
✓ radiation (e.g. ultraviolet and ionizing); and
✓ rapid changes in atmospheric pressure.
3. CHEMICALS AND DRUGS
An ever-increasing list of chemical agents and drugs may cause cell injury. Important examples include
the following:
✓ chemical poisons such as cyanide, arsenic, mercury;
✓ strong acids and alkalis;
✓ environmental pollutants;
✓ insecticides and pesticides;
✓ oxygen at high concentrations;
✓ hypertonic glucose and salt;
✓ social agents such as alcohol and narcotic drugs; and therapeutic administration of drugs.
8. 8 Cell Injury - Pathophysiology
4. MICROBIAL AGENTS
Injuries by microbes include infections caused by bacteria, rickettsia, viruses, fungi, protozoa, metazoan,
and other parasites.
5. IMMUNOLOGIC AGENTS
Immunity is a ‘double edged sword’ it protects the host against various injurious agents but it may also
turn lethal and cause cell injury e.g.
✓ hypersensitivity reactions;
✓ anaphylactic reactions; and
✓ autoimmune diseases.
✓ Immunologic tissue injury
6. NUTRITIONAL DERANGEMENTS
A deficiency or an excess of nutrients may result in nutritional imbalances. Nutritional deficiency diseases
may be due to overall deficiency of
nutrients (e.g. starvation),
protein calorie (e.g. marasmus, kwashiorkor),
minerals (e.g. anemia),
or trace elements.
Nutritional excess is a problem of affluent societies resulting in obesity, atherosclerosis, heart disease and
hypertension.
7. AGING
Cellular aging or senescence leads to impaired ability of the cells to undergo replication and repair, and
ultimately lead to cell death culminating in death of the individual.
8. PSYCHOGENIC DISEASES
There are no specific biochemical or morphologic changes in common acquired mental diseases due to
mental stress, strain, anxiety, overwork and frustration e.g. depression, schizophrenia. However,
problems of drug addiction, alcoholism, and smoking result in various organic diseases such as liver
damage, chronic bronchitis, lung cancer, peptic ulcer, hypertension, ischemic heart disease etc.
9. IATROGENIC CAUSES
Although as per Hippocratic oath, every physician is bound not to do or administer anything that causes
harm to the patient, there are some diseases as well as deaths attributed to iatrogenic causes (owing to
physician). Examples include occurrence of disease or death due to error in judgment by the physician
and untoward effects of administered therapy (drugs, radiation)
10. IDIOPATHIC DISEASES
Idiopathic means “of unknown cause”. Finally, although so much is known about the etiology of diseases,
there still remain many diseases for which exact cause is undetermined. For example, most
common form of hypertension (90%) is idiopathic (or essential) hypertension. Similarly, exact etiology of
many cancers is still incompletely known.
9. 9 Cell Injury - Pathophysiology
Pathogenesis of Ischemic and Hypoxic injury
Figure 3: Sequence of events in the pathogenesis of reversible and irreversible cell injury caused by hypoxia/ischemia.
Hydroxyl radicle Mechanism of cell injury
Figure 4: Mechanism of cell death by hydroxyl radical, the most reactive oxygen species.
10. 10 Cell Injury - Pathophysiology
MORPHOLOGY OF CELL INJURY
After having discussed the mechanisms of various forms of cell injury, we now turn to light microscopic
morphologic changes of reversible and irreversible cell injury. Depending upon the severity of cell injury,
degree of damage and residual effects on cells and tissues are variable. In general, morphologic changes
in various forms of cell injury can be classified as:
Morphology of Reversible cell injury:
Following morphologic forms of reversible cell injury are included under this heading:
1. Hydropic change (cloudy swelling, or vacuolar degeneration)
2. Fatty change
3. Hyaline change
4. 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). The common causes are bacterial toxins, chemicals,
poisons, burns, high fever, intravenous administration of hypertonic glucose or saline etc. Cloudy swelling
results from impaired regulation of sodium and potassium at the level of cell membrane. This results in
intracellular accumulation of sodium and escape of potassium. This, in turn, leads to rapid flow of water
into the cell to maintain iso-osmotic conditions and hence cellular swelling occurs.
Fatty Change (Steatosis): It is the intracellular accumulation of neutral fat within parenchymal cells. Liver
is the commonest site for accumulation of fat because it plays central role in fat metabolism. Fatty change
in the liver may result from one of the two types of causes:
1. Conditions with excess fat (hyperlipidemia), exceeding the capacity of the liver to metabolize it.
2. Liver cell damage, when fat cannot be metabolized in it.
11. 11 Cell Injury - Pathophysiology
Hyaline Change: The word ‘hyaline’ means glassy (hyalos = glass). Hyaline change is associated with
heterogeneous pathologic conditions. It may be intracellular or extracellular.
Intracellular hyaline is mainly seen in epithelial cells. A few examples are as follows:
1. Hyaline droplets in the proximal tubular epithelial cells in cases of excessive reabsorption of plasma
proteins.
2. Hyaline degeneration of rectus abdominis muscle called Zenker’s degeneration, occurring in typhoid
fever. The muscle loses its fibrillar staining and becomes glassy and hyaline.
3. Nuclear or cytoplasmic hyaline inclusions seen in some
viral infections.
Extracellular hyaline is seen in connective tissues. A few examples are as under:
1. Hyaline degeneration in leiomyomas of the uterus.
2. Hyaline arteriolosclerosis in renal vessels in hypertension and diabetes mellitus.
3. Hyalinized glomeruli in chronic glomerulonephritis.
Mucoid Changes: Mucus secreted by mucous glands is a combination of proteins complexed with
mucopolysaccharides. Mucin, a glycoprotein, is its chief constituent. Mucin is normally produced by
epithelial cells of mucous membranes and mucous glands, as well as by some connective tissues like in
the umbilical cord.
EPITHELIAL MUCIN: Following are some examples of functional excess of epithelial mucin:
1. Catarrhal inflammation of mucous membrane (e.g. of respiratory tract, alimentary tract, uterus).
2. Obstruction of duct leading to mucocele in the oral cavity and gallbladder.
3. Cystic fibrosis of the pancreas.
4. Mucin-secreting tumors (e.g. of ovary, stomach, large bowel, etc.)
CONNECTIVE TISSUE MUCIN: A few examples of disturbances of connective tissue mucin are as under:
1. Mucoid or myxoid degeneration in some tumors e.g. myxomas, neurofibromas, fibroadenoma, soft
tissue sarcomas, etc.
2. Myxoid change in the synovium in ganglion on the wrist.
SUBCELLULAR ALTERATIONS IN CELL INJURY
These occur at the level of cytoskeleton, lysosomes, endoplasmic reticulum and mitochondria.
1. CYTOSKELETAL CHANGES: Components of cytoskeleton may show the following morphologic
abnormalities:
i) Defective microtubules:
a. Poor sperm motility causing sterility.
b. Immotile cilia syndrome: Immotile cilia of respiratory tract and consequent chronic infection due
to defective clearance of inhaled bacteria.
ii) Defective microfilaments:
a. In myopathies
b. Muscular dystrophies
iii) Accumulation of intermediate filaments:
Various classes of intermediate filaments may accumulate in the cytosol.
For example: Neurofibrillary tangles in Alzheimer’s disease are composed of neurofilaments and paired
helical filaments.
12. 12 Cell Injury - Pathophysiology
2. LYSOSOMAL CHANGES: Lysosomes contain powerful hydrolytic enzymes. Heterophagy and autophagy
are the two ways by which lysosomes show morphologic changes of phagocytic function.
i) Heterophagy: Phagocytosis (cell eating) and pinocytosis (cell drinking) are the two forms by which
material from outside is taken up by the lysosomes of cells such as polymorphs and macrophages to form
phagolysosomes. This is termed heterophagy. Microbial agents and foreign particulate material are
eliminated by this mechanism.
ii) Autophagy: This is the process by which worn out intracellular organelles and other cytoplasmic
material form autophagic vacuole that fuses with lysosome to form autophago-lysosome.
iii) Indigestible material: Some indigestible exogenous particles such as carbon or endogenous substances
such as lipofuscin may persist in the lysosomes of the cells for a long time as residual bodies.
iv) Storage diseases: A group of lysosomal storage diseases due to hereditary deficiency of
enzymes may result in abnormal collection of metabolites in the lysosomes of cells.
3. SER CHANGES: Hypertrophy of smooth endoplasmic reticulum of liver cells as an adaptive change may
occur in response to prolonged use of barbiturates.
4. MITOCHONDRIAL CHANGES: Mitochondrial injury plays an important role in cell injury. Morphologic
changes of cell injury in mitochondria may be seen in the following conditions:
i) Megamitochondria: Megamitochondria consisting of unusually big mitochondria are seen in alcoholic
liver disease and nutritional deficiency conditions.
ii) Alterations in the number of mitochondria may occur. Their number increases in hypertrophy and
decreases in atrophy.
iii) Oncocytoma in the salivary glands, thyroid and kidneys consists of tumor cells having very large
mitochondria.
iv) Myopathies having defect in mitochondria have abnormal cristae.
Accumulation of Various components inside the cell:
Cholesterol Deposits: As in Atherosclerosis, the foam cell deposits
Protein Deposits: As in proteinuria, antitrypsin deficiency, etc.
Glycogen Deposits: As in diabetes melitus and GCD (glycogen storage disease)
Pigment Deposits: Endogenous Pigments (Melanin, Hemoprotein, Lipofuscin) causing disease like
alkaptonuria, albinism, etc. and Exogenous pigments (Pollutants, Metals (lead, silver), Ink of Tattoo)
causing several toxicities in cell.
13. 13 Cell Injury - Pathophysiology
CELLULAR ADAPTATIONS
For the sake of survival on exposure to stress, the cells make adjustments with the changes in their
environment (i.e. adapt) to the physiologic needs (physiologic adaptation) and to non-lethal pathologic
injury (pathologic adaptation).
In general, the adaptive responses are reversible on withdrawal of stimulus. However, if the irritant
stimulus persists for long time, the cell may not be able to survive and may either die or progress further
e.g. cell death may occur in sustained atrophy; dysplasia may progress into carcinoma in situ. Thus, the
concept of evolution ‘survival of the fittest’ holds true for adaptation as ‘survival of the adaptable’.
Figure 5: Cellular adaptation forms
Five basic adaptations that a cell undergoes as depicted in figure are as follows:
1. Hyperplasia
2. Hypertrophy
3. Atrophy
4. Metaplasia
5. Dysplasia
1. 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. Hyperplasia occurs due to increased recruitment of cells for any function.
A. Physiological:
14. 14 Cell Injury - Pathophysiology
a. Hormonal: Influence of hormonal stimulation. Hyperplasia of the female breast
epithelium at puberty or in pregnancy pregnant uterus, normal endometrium after a
normal menstrual cycle.
b. Compensatory: hyperplasia occurring following removal of part of an organ, like
Regeneration of the liver following partial hepatectomy, Regeneration of epidermis
after skin abrasion, nephrectomy on one side, there is hyperplasia of nephrons of the
other kidney.
B. Pathological: Excessive stimulation of hormones or growth factors, as in Endometrial
hyperplasia, wound healing - of granulation tissue due to proliferation of fibroblasts and
endothelial cells. Skin warts from hyperplasia of epidermis due to human papilloma virus.
Pseudo carcinomatous hyperplasia of the skin.
2. Hypertrophy: 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.
In both cases, it is caused either by increased functional demand or by hormonal stimulation.
Hypertrophy without accompanying hyperplasia affects mainly muscles. In nondividing cells too,
only hypertrophy occurs.
A. Physiologic hypertrophy. Enlarged size of the uterus in pregnancy is an excellent example of
physiologic hypertrophy as well as hyperplasia.
B. Pathologic hypertrophy. Hypertrophy in cardiac muscle may occur in a number of
cardiovascular diseases. Due to increased function of cells of heart.
The relationship between hyperplasia and hypertrophy: Although hypertrophy and hyperplasia are two
distinct processes, frequently both occur together, and they well be triggered by the same mechanism.
3. Atrophy: Reduction of the number and size of parenchymal cells of an organ or its parts which
was once normal is called atrophy (compared from hypoplasia which is the term used for
developmentally small size, and aplasia for extreme failure of development so that only
rudimentary tissue is present).
A. Physiologic Atrophy: Atrophy is a normal process of aging in some tissues, which could be due to
loss of endocrine stimulation or arteriosclerosis. For example:
✓ Atrophy of lymphoid tissue in lymph nodes, appendix and thymus.
✓ Atrophy of gonads after menopause.
✓ Atrophy of brain with aging.
B. Pathological Atrophy: The Causes are as under:
a. Starvation atrophy. In starvation, there is first depletion of carbohydrate and fat stores
followed by protein catabolism. There is general weakness, emaciation and anemia referred
to as cachexia seen in cancer and severely ill patients.
15. 15 Cell Injury - Pathophysiology
b. Ischemic atrophy. Gradual diminution of blood supply due to atherosclerosis may result in
shrinkage of the affected organ e.g. i) Small atrophic kidney in atherosclerosis of renal artery.
ii) Atrophy of brain in cerebral atherosclerosis.
c. Disuse atrophy: Prolonged diminished functional activity is associated with disuse atrophy of
the organ e.g. Wasting of muscles of limb immobilized in cast or Atrophy of the pancreas in
obstruction of pancreatic duct.
d. Neuropathic atrophy. Interruption in nerve supply leads to wasting of muscles e.g.
Poliomyelitis, Motor neuron disease and Nerve section.
e. Endocrine atrophy. Loss of endocrine regulatory mechanism results in reduced metabolic
activity of tissues and hence atrophy e.g. Hypopituitarism may lead to atrophy of thyroid,
adrenal and gonads. Or Hypothyroidism may cause atrophy of the skin and its adnexal
structures.
f. Pressure atrophy. Prolonged pressure from benign tumors or cyst or aneurysm may cause
compression and atrophy of the tissues e.g. Erosion of spine by tumor in nerve root. Erosion
of sternum by aneurysm of arch of aorta.
g. Idiopathic atrophy. There are some examples of atrophy where no obvious cause is present
e.g. Myopathies, Testicular atrophy.
4. Metaplasia: Metaplasia is a reversible change in which one adult cell type is replaced by another
adult cell type. It is Loss of Differentiation property of cell. Causes: Changes in environment,
Irritation or inflammation or Nutritional. For Example: Squamous cells turn into Columnar cells:
Intestinal metaplasia in healed chronic gastric ulcer and Barrett’s esophagus.
5. 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 characterized by cellular proliferation and cytologic changes:
✓ Increased number of layers of epithelial cells
✓ Disorderly arrangement of cells from basal layer to the surface layer
✓ Loss of basal polarity i.e. nuclei lying away from basement membrane
✓ Cellular and nuclear pleomorphism
✓ Increased nucleocytoplasmic ratio
✓ Nuclear hyperchromatism
✓ Increased mitotic activity.
The two most common examples of dysplastic changes are the uterine cervix and respiratory
tract.
16. 16 Cell Injury - Pathophysiology
CELL DEATH (IRREVERSIBLE CELL INJURY)
Cell death is a state of irreversible injury. It may occur in the living body as a local or focal change
(i.e. autolysis, necrosis and apoptosis) and the changes that follow it (i.e. gangrene and pathologic
calcification), or result in end of the life (somatic death). These pathologic processes involved in
cell death are described below.
NECROSIS: A localized area of death of tissue followed by degradation of tissue by hydrolytic
enzymes liberated from dead cells; it is invariably accompanied by inflammatory reaction. This
series of events of spontaneous death of group of cells or tissue is termed as Necrosis.
Necrosis can be caused by various agents such as hypoxia, chemical and physical agents, microbial
agents, immunological injury, etc. NOTE: Necrosis can only be pathologic, whereas apoptosis can
be physiological or pathological.
Two essential changes characterize irreversible cell injury in necrosis of all types:
1. Denaturation of proteins (Structural & Functional): Structural proteins are denatured and
hence structural integrity of cell is lost and membrane degenerates causing leak of protease
enzymes, leading to more protein digestion in nearby cells also.
NOTE: Necrosis cannot occur in Single cell, it always affects group of cells or tissue because of
leakage, whereas apoptosis can occur in selective cell.
2. Cell digestion by lytic enzymes (Autolysis & Heterolysis): Autolysis is degeneration by self-
released enzymes and heterolysis is degeneration by enzymes of pathogens.
Types of Necrosis: Coagulative, Liquefaction, Caseous, Fat and Fibrinoid
A. Coagulative: This is the most common type of necrosis caused by irreversible focal injury,
mostly from sudden cessation of blood flow (ischemia), and less often from bacterial and
chemical agents. The organs commonly affected are the heart, kidney, and spleen.
B. Liquefaction: also called colliquative necrosis occurs commonly due to ischemic injury and
bacterial or fungal infections. It occurs due to degradation of tissue by the action of powerful
hydrolytic enzymes. The common examples are infarct brain and abscess cavity.
C. Caseous: Caseous necrosis is found in the center of foci of tuberculous infections. It combines
features of both coagulative and liquefactive necrosis. Microscopically it looks like cheese.
D. Fat: Fat necrosis is a special form of cell death occurring at two anatomically different
locations but morphologically similar lesions. These are: following acute pancreatic necrosis,
and traumatic fat necrosis commonly in breasts.
E. Fibrinoid: Fibrinoid necrosis is characterized by deposition of fibrin-like material which has
the staining properties of fibrin. It is encountered in various examples of immunologic tissue
injury (e.g. in immune complex vasculitis, autoimmune diseases, Arthus reaction etc.),
arterioles in hypertension, peptic ulcer etc.
17. 17 Cell Injury - Pathophysiology
APOPTOSIS: Apoptosis is a form of ‘coordinated and internally programmed cell death’
having significance in a variety of physiologic and pathologic conditions (apoptosis is a Greek
word meaning ‘falling off’ or ‘dropping off’). The term was first introduced in 1972 as distinct
from necrosis by being 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.
Physiologic Processes:
1. Organized cell destruction in sculpting of tissues during development of embryo.
2. Physiologic involution of cells in hormone-dependent tissues e.g. endometrial shedding,
regression of lactating breast after withdrawal of breast-feeding.
3. Normal cell destruction followed by replacement proliferation such as in intestinal
epithelium.
4. Involution of the thymus in early age.
Pathologic Processes:
1. Cell death in tumors exposed to chemotherapeutic agents.
2. Cell death by cytotoxic T cells in immune mechanisms such as in graft-versus-host disease
and rejection reactions.
3. Progressive depletion of CD4+T cells in the pathogenesis of AIDS.
4. Cell death in viral infections e.g. formation of Councilman bodies in viral hepatitis.
5. Pathologic atrophy of organs and tissues on withdrawal of stimuli e.g. prostatic atrophy
after orchiectomy, atrophy of kidney or salivary gland on obstruction of ureter or ducts,
respectively.
6. Cell death in response to injurious agents involved in causation of necrosis e.g. radiation,
hypoxia and mild thermal injury.
7. In degenerative diseases of CNS e.g. in Alzheimer’s disease, Parkinson’s disease, and chronic
infective dementias.
Mechanism of Apoptosis: 1. Initiation 2. Execution 3. Phagocytosis
1. Initiation: This step generally initiates activation of CASPASE by two mechanisms:
A. Extrinsic Pathway: Regulated by External factor such as T-Lymphocyte, it activates FAS-FADD
pathway and activates CASPASE CASCADE
B. Intrinsic Pathway: Regulated by internal factor, BCL2 and BAX Proteins initiates leakage of
Cytochrome C from mitochondria, which further activates CASPASE CASCADE
2. Execution: Lots of Caspases are activated and they break cell into various parts, in very organized
manner such that no enzyme or any component leaks out. Plasma membrane itself surrounds
various parts that are broken down into pieces. There is formation of Apoptotic Blebs. The plasma
membrane of the apoptotic cell remains intact, but the membrane is altered in such a way that
the cell and its fragments become avid targets for phagocytes.
3. Phagocytosis: Phagosomes identify these blebs and engulf it to digest the dead cell.
18. 18 Cell Injury - Pathophysiology
SUMMARY OF PROCESSES:
Figure 6: Apoptosis Mechanism
Figure 7: Comparison of Necrosis and Apoptosis
For Animated video on Apoptosis Click Here: https://www.youtube.com/watch?v=-vmtK-bAC5E
19. 19 Cell Injury - Pathophysiology
FAQ (Frequently asked questions):
Q1. Enlist the etiological factors of Cell injury and explain mechanism of injury caused by radiation.
Q2. Explain mechanism of hypoxic and ischemic cell injury.
Q3. Explain Morphology of cell undergoing Reversible injury
Q4. What are subcellular alterations in cell injury? Write a brief note.
Q5. Explain various modes of Cellular adaptations with suitable examples.
Q6. Explain the molecular concept of Programmed cell death.
Q7. What is Necrosis? and How many types of necrosis are there?
Q8. Write in brief about the difference between Apoptosis and Necrosis.
Self-Evaluation Test
(If you are able to define all the following terms you are crystal clear with this chapter)
Pathology Physiology Pathophysiology Disease
illness Syndrome Etiology Iatrogenic
Idiopathic Adaptation Hypoxia Ischemia
Hydropic Change Steatosis Hyaline change Mucoid Change
Autophagy Hyperplasia Metaplasia Dysplasia
Hypertrophy Atrophy Hypoplasia Necrosis
Apoptosis Phagocytosis Pinocytosis Apoptotic Blebs