The Human Body PJ1311 Lecture 2 - Cell Death PDF

The Human Body PJ1311 Lecture 2: Cell Death Dr Alina Oknianska 1 Learning Objectives and Exam Revision Advice You should be able to discuss cell death and various mechanisms of cell injury and cellular response to stress and cell injury...

The Human Body PJ1311 Lecture 2: Cell Death Dr Alina Oknianska 1 Learning Objectives and Exam Revision Advice You should be able to discuss cell death and various mechanisms of cell injury and cellular response to stress and cell injury 2  Overview of Cellular Response to Stress and Injury Cells active in the environment Constantly changing to meet demands and extracellular stresses Maintain normal homeostasis Cells encounter physiologic stresses or pathologic stimuli Adaptation – preserve viability and function 3  Overview of Cellular Response to Stress and Injury If adaptive ability exceeded or external stress is harmful – causes cell injury Cell injury reversible within certain limits Severe or persistent stress results in irreversible injury and cell death Cell death: essential process in normal cells and key aspect of development 4 Overview of Cellular Response to Stress and Injury 5  Causes of Stress and Injury Grouped into categories Oxygen deprivation (hypoxia) Chemical agents Infectious agents Immunological reactions Genetic Defects Protein deficiencies (enzymes), 6  Causes of Stress and Injury Grouped into categories Nutritional imbalances Effects on cells and growth Physical agents Trauma, change in temperature, pH etc Aging 7  Cellular Adaptations to Stress Adaptations – reversible changes to cells in response to environmental changes Physiological adaptations Response to normal stimulation – hormones and chemical mediators Pathological adaptations Response to stress – modulate structure and function to escape injury 8  Cellular Adaptations to Stress : Pathological Adaptations The most common morphologically apparent adaptive changes are Hypertrophy (increase in cell size) Hyperplasia (increase in cell number) Atrophy (decrease in cell size) Metaplasia (change in cell type) 9  Cellular Adaptations to Stress : Hypertrophy Increase in size of the cells – increase in organ size No new cells – just bigger Due to increased amounts structural proteins and organelles Happens when non dividing cells exposed to stress E.g. myocardium and skeletal muscle cells 10  Cellular Adaptations to Stress : Hypertrophy Physiologic or pathogenic Caused by increased functional demand or specific hormonal stimulation Example Weightlifter develop muscles by hypertrophy of skeletal muscles – increased workload 11  Cellular Adaptations to Stress : Hypertrophy Example Cardiac enlargement due to constant strain of high blood pressure (hypertension) 12  Cellular Adaptations to Stress : Pathological Adaptations The most common morphologically apparent adaptive changes are Hypertrophy (increase in cell size) Hyperplasia (increase in cell number) Atrophy (decrease in cell size) Metaplasia (change in cell type) 13  Cellular Adaptations to Stress : Hyperplasia Increase in number of the cells – increase in organ size Only occurs in cells capable of replication May occur with hypertrophy in response to similar stimuli Physiologic or pathologic 14  Cellular Adaptations to Stress : Hyperplasia Physiologic hyperplasia Hormonal hyperplasia – e.g. development of female breast during puberty and pregnancy Compensatory hyperplasia – e.g. portion of organ removed (liver) Pathologic hyperplasia Excessive hormone or growth factor stimulation e.g. HPV causes skin warts 15  Cellular Adaptations to Stress : Hyperplasia If becomes irreversible – dysplasia Leads to cancer 16  Cellular Adaptations to Stress : Pathological Adaptations The most common morphologically apparent adaptive changes are Hypertrophy (increase in cell size) Hyperplasia (increase in cell number) Atrophy (decrease in cell size) Metaplasia (change in cell type) 17  Cellular Adaptations to Stress : Atrophy Decrease in size of cells (shrink) by loss of cell substance – decrease in size of organ Reduced protein synthesis and increased degradation Cells have reduced function BUT not dead Often accompanied by autophagy (“self eating”) 18  Cellular Adaptations to Stress : Atrophy Physiologic and pathogenic Decreased workload – e.g. immobilisation of limb in fracture cast Aging and reduced blood supply 19  Cellular Adaptations to Stress : Pathological Adaptations The most common morphologically apparent adaptive changes are Hypertrophy (increase in cell size) Hyperplasia (increase in cell number) Atrophy (decrease in cell size) Metaplasia (change in cell type) 20  Cellular Adaptations to Stress : Metaplasia Reversible change – one cell type replaced by another Cells sensitive to particular stress replaced by other more resistant cell type. Believed to be result of “genetic reprogramming” of stem cells Most common in epithelial cells – short lived and replaced from stem cells May result in reduced function or increased21  Cellular Adaptations to Stress : Metaplasia Example – squamous change in respiratory epithelium of cigarette smokers 22 Cellular Adaptations to Stress : Summary 23  Overview of Cell Injury and Cell Death Cell injury results when severely stressed cells no longer able to adapt or exposed to inherently damaging agents 24  Mechanisms of Cell Injury Main sites of damage in cell injury 25  Overview of Cell Injury and Cell Death : Reversible Cell Injury Early stage or mild forms of injury Functional and morphological changes reversible if stimulus removed 26  Overview of Cell Injury and Cell Death : Reversible Cell Injury Morphological changes in reversible cell injury e.g. kidney tubules – swelling of cells and surface blebs Normal Reversible 27  Overview of Cell Injury and Cell Death : Reversible Cell Injury Changes in reversible cell injury e.g. DNA damage – cell cycle arrest 28  Overview of Cell Injury and Cell Death : Cell Death Continuing damage – injury becomes irreversible 29  Overview of Cell Injury and Cell Death : Cell Death Changes in irreversible cell injury e.g. DNA damage and aging – senescence permanent cell cycle arrest in G1 Large flatten cells Increased vacuoles Cytoplasmic granularity 30  Overview of Cell Injury and Cell Death : Cell Death Morphological changes in irreversible cell injury e.g. kidney tubules – loss of nuclei, fragmentation of cells and leakage of Normal contents Reversible Irreversible 31 Overview of Cell Injury and Cell Death : Cell Death 32  Overview of Cell Injury and Cell Death : Cell Death Two types of cell death 33  Overview of Cell Injury and Cell Death : Cell Death Necrosis Major pathway of cell death in many commonly encountered injuries Always a pathological process Apoptosis Cell deprived of growth factors DNA or proteins damaged beyond repair Has many normal functions – not always associated with injury 34 Overview of Cell Injury and Cell Death : Cell Death 35  Cell Death : Necrosis Degradative actions of enzymes on lethally injured cells Morphological alterations Nuclear shrinkage, fragmentation and dissolution Breakdown of plasma and organelle membranes 36  Cell Death : Necrosis Necrosis of collection of cells in tissue or organ Death of tissue or sometimes entire organ Kidney infarct (yellow) 37  Cell Death : Necrosis Necrosis of collection of cells in tissue or organ Death of tissue or sometimes entire organ Brain and lung (tuberculous) 38 Overview of Cell Injury and Cell Death : Cell Death 39  Cell Death : Apoptosis Activated by tightly controlled suicide program Cell activate enzymes which degrades itself Plasma membrane remains intact but is recognised by phagocytes No cellular contents leaks out No inflammatory response 40  Cell Death : Apoptosis Morphological alterations Cell shrinkage and chromatin condensation Membrane blebbing and nuclear fragmentation Apoptotic body formation Phagocytosis by surrounding tissue 41  Cell Death : Apoptosis https://www.youtube.com/watch?v=NwkHcwIoBRg https://www.youtube.com/watch?v=1vaEVcMfa1E 42  Cell Death : Apoptosis Induced by both physiological and pathological conditions Physiological conditions Eliminate cells no longer needed and maintain cell populations in tissue. Pathologic conditions Eliminates cells genetically altered or injured beyond repair No host reaction – damage contained 43  Cell Death : Apoptosis Mechanisms of apoptosis 44 Thank You! 45