Cellular Adaptations and Cell Death 2022 Part 2 PDF

Cellular Adaptations and Cell Death: Part 2 Cellular Responses to Injury and Stress Reversible if stimulus minor, transient and removed...

Cellular Adaptations and Cell Death: Part 2 Cellular Responses to Injury and Stress Reversible if stimulus minor, transient and removed Normal Cell Inherentl y STRES injurious S stimulus Stress exceeds Adaptation adaptabilit Cell Injury y Irreversib Severe and le progressive Cell death is Cell Death: the key event Apoptosis or in the Necrosis development of many Causes of Cell Injury and Death Oxygen Deprivatio n Nutritiona l Physical Imbalance Agents s Cell Injur y Chemical Immune s and Reactions Drugs Infectious Agents  Causes of cell injury – Oxygen deprivation Oxygen deprivation is HYPOXIA and is impairs aerobic metabolism It can be a solitary phenomenon – Oxygen problems e.g. altitude – Haemoglobin problems e.g. anaemia  Causes of cell injury – Oxygen deprivation It can reflect problems with blood supply, this is called: Ischaemia – Local e.g. embolus – Systemic e.g. cardiac failure Ischaemia is worse than hypoxia as there loss of delivery of other elements e.g. nutrients and build up of toxins and so cell injury is quicker and more severe Ischaemia- Atheresclerosis Causes of cell injury - Physical  Physical: Heat or Cold Cell homeostasis- temperature Changes- metabolic pathways and protein structure Heat: Coagulate/breakdown protein Cell necrosis Disruption of skin- infection and loss of water Degrees Cold: Frostbite Ischaemia- vasoconstriction, coagulation Ice crystals  Physical- Electrical Direct damage to cells Current path- path of least resistance Heart- change the rhythm -> cardiac arrest  Causes of cell injury - Chemical Chemicals can damage cells: – Directly – As a result of metabolism and generation of breakdown products The main modes of damage by chemicals are: – Perturbation of the osmotic environment of cell – Disruption of biochemical reactions e.g. if ATP levels drop below critical levels, affected cells will die – Compromising the integrity of the cell membrane Chemicals that cause damage range from oxygen and water up to poisons  Chemical- Corrosive substances Direct injury Acid – Coagulation- denatured proteins – Eschar- less penetration Base – Liquefies- denature proteins and liquefy fat – Deep penetration  Chemical- Paracetamol Indirect injury 3 pathways of breakdown – Glucuronidation – Sulfation – N-hydroxylation- toxic metabolite OD – Glucuronidation + Sulfation saturated – Build up of toxic NAPQI – cell membrane damage  Causes of cell injury - Infections From Fungi, Rickettsiae to Prions – E.g. viruses can take over the protein production machinery and subvert it entirely to the production of new virions  Infections: Bacterial Direct injury – E. coli- UTIs an directly lyse urinary tract cells- enzyme – Exotoxins- released by bacterium- Botulinum Indirect – Innate immune response- neutrophils can destroy normal tissue – pneumonia – Endotoxins- released by dead bacterium- stimulate inflammatory response  Infections: Viral Infect cells – Replication Infected cell death – Apoptosis – Killed by immune system Causes of cell injury – Immune  Immune- Allergies Hypersensitivity- acute is Type 1 Allergen – Urticarial rash – Anaphylaxis Causes of cell injury - Nutrition  Nutrition- insufficiency Vitamin C deficiency- Scurvy  Nutrition- Excess Vitamin A toxicity – Liver toxicity – General symptoms- headache, nausea, yellow discolouration of skin Obesity – Insulin resistance – Arterial disease Cellular Responses to Injury and Stress Reversible if stimulus minor, transient and removed Normal Cell Inherentl y STRES injurious S stimulus Stress exceeds Adaptation adaptabilit Cell Injury y Irreversib Severe and le progressive Cell death is Cell Death: the key event Apoptosis or in the Necrosis development of many  Types of Cell Death APOPTOSIS NECROSIS Pathologic or physiologic Pathologic Internally controlled Enzymatic cell Nuclear dissolution digestion Cell contents leak out  Apoptosis Physiological Pathological Embryogenesis Cells with DNA Involution of hormone damage dependent tissue Cells with Endoplasmic Cell loss in Reticulum Stress proliferating cell Some infections e.g. populations Viruses Elimination potentially Pathological atrophy if harmful lymphocytes a duct is obstructed Cells no longer required Apoptosis Apoptosis  Necrosis Coagulati ve Liquefacti Fibrinoid ve Tissue Necros is Fat Caseous Gangreno us  Coagulative Cells are non-vital i.e. the nucleus is not identifiable but the structure of the tissue still visible histologically Reflects cell death WITHOUT enzymatic digestion of the tissues Commonly seen in ischaemic injuries (except in the brain)  Liquefactive Tissue is replaced by liquefied material Reflects cell death accompanied with enzymatic digestion of the tissues e.g. post inflammation NB: Brain is the exception as liquefactive necrosis is seen post ischaemia due to lack of architecture of tissue Caseous Looks like cottage cheese Seen in infection with Tuberculosis Gangrenous Necrosis of limb- often lower leg Coagulative necrosis- multilayer +/- Liquefactive necrosis (wet gangrene)  Fat Necrosis of adipocytes- pancreatitis/breast Breakdown of fat cells -> fatty acid leakage -> bind to calcium (fat saponification) Inflammatory reaction Fibrinoid Immune-mediated- complexes of antigens and antibodies in vessel walls Complexes + fibrin leak out of vessel walls Vasculitis Learning Outcomes Describe physiological and pathological examples of hyperplasia, hypertrophy, atrophy and metaplasia Define the terms dysplasia and neoplasia Explain the patterns of cellular adaptation seen secondary to non-lethal cell damage Outline the causes and patterns of cellular response to noxious stimuli Outline the mechanisms and targets of cell damage Thank you