Cell injury, apoptosis & death I 2024 - Copy.pptx

Cell injury, apoptosis & death - I  Diagnosis of disease  Cell injury and death  Mechanisms of cell injury Learning outcomes  To know the main approaches to diagnose a disease  To understand the concept of cell injury and cell death  To describe mechanisms of cell injury Cell injury, apoptosis...

Cell injury, apoptosis & death - I  Diagnosis of disease  Cell injury and death  Mechanisms of cell injury Learning outcomes  To know the main approaches to diagnose a disease  To understand the concept of cell injury and cell death  To describe mechanisms of cell injury Cell injury, apoptosis & death - I  Diagnosis of disease  Cell injury and death  Mechanisms of cell injury Diagnosis To identify (diagnose) a disease in an individual 1. Clinic history to document symptoms 2. Examine the patient for clinic signs 3. Performing investigations Diagnostic laboratory test To be made on a sample from a patient, and the results help to allocate the case to a diagnostic group 1. Quantitative measurement: interpreted in relationship to a “normal” range of values 2. Subjective assessment: based on the assessment of a pathologist Diagnostic laboratory test Serum insulin level test Diagnostic laboratory test Cervical epithelial cells (slide) Epidemiological approach The study of disease in populations and the distribution of diseases in relation to place and time  Identification of the possible causes and modes of acquisition of disease  Involves recording and analysis of data about a disease in groups of people rather than in an individual alone Epidemiology Aims:  Providing aetiological clues to the causes of disease  Planning preventive measures  Provision of adequate medical facilities  Population screening for early diagnosis Example of epidemiology Hepatitis Delta Virus (HDV) Example of epidemiology Age-specific prevalence of coronary heart diseases - Australia 2004-05 Basic approaches Epidemiology establishes the association between a risk factor and the occurrence of a disease but not the causal relationship  Prospective studies  Subjects followed over time  Risk factors monitored  Relative risk determined  Retrospective studies  Looking backward over a period of time  Past exposure to suspected aetiological factors examined  Odds ratio determined  Cross-sectional studies  Prevalence between different populations at a particular time  Mainly for public health planning  Assess the association between risk factors and a disease, but limited In lecture case study and discussion A researcher is studying a disease and finds that the relative risk of developing the disease for people who drink coffee is 0.5. Which of the following conclusions is most appropriate? a) Coffee drinkers are four times as likely to develop the disease as those who do not drink coffee b) Coffee drinkers are twice likely to develop the disease as those who do not drink coffee c) Those who do not drink coffee are twice as likely to develop the disease as coffee drinkers d) Those who do not drink coffee are four times as likely to develop the disease as coffee drinkers e) Coffee is the most likely cause of the disease Autopsies  May be performed for legal or medical purpose  Information can be used for clinical audit, education, medical research  Diagnostic discrepancies are revealed by autopsies in ~30% of cases Autopsies Medicolegal autopsies: To determine the cause of death To collect evidence that may be used in the prosecution of those alleged to be responsible for the death To be performed by state forensic pathologists Autopsies Clinical autopsies (Non-medicolegal): On patients who die in hospital with unclear diagnosis or other reasons, but very useful information can be gathered from autopsies In class MCQ test Medico-legal autopsies are only performed by: a) Forensic scientists b) Home Office pathologists c) General practitioners d) Coroners e) Police officer Cell injury, apoptosis & death - I  Diagnosis of disease  Cell injury and death  Mechanisms of cell injury Cellular injury and cell death  Normal cells adapt in response to challenges to meet new demands  Cell Injury: If challenge is too great, or for too long, cells fail to meet this demand and show signs of injury: change or loss of function; change of morphology 1) Reversible 2) Irreversible  Irreversibly injured cells undergo further morphologic changes, recognized as cell death 1) Necrosis 2) Apoptosis Progress and changes in cell Injury Endoplasmic reticulum Nucleus Mitochondria injury recovery Reversible ER, mitochondri a swelling Chromatin clamping Death Necrosis Irreversible Cell injury, apoptosis & death - I  Diagnosis of disease  Cell injury and death  Mechanisms of cell injury Causes of cell injury  Oxygen deprivation: Hypoxia; Ischemia  Physical agents: Mechanical trauma; Extreme temperature Chemical agents and Drugs: Cyanide; CO; Alcohol Infectious agents: Viruses; Bacteria; Immunologic reactions: Anaphylactic reaction to a protein Nutritional imbalances: Deficiencies of specific vitamins; Undernutrition and overnutrition Genetic derangements: Sickle cell anaemia      Mechanisms of cell injury Complex and unknown in many cases Principles in the study of cell injury:    Cellular response to stimuli depends on: the type, severity and duration of injury Consequences of injury depends on: the type, state and adaptability of injured cells Cell injury results from functional and biochemical abnormalities in one or several of essential cellular components Injury by oxygen-derived free radicals (Reactive oxygen species, ROS) Definition: Free radicals are chemical species with a single unpaired electron in the outer orbit e.g. ®  ROS Generation: (within cells) - Absorption of radiant energy: ultraviolet light, x-rays - Reduction-oxidation reactions - Transition metals donate or accept free electrons during intracellular reactions: H2O2 + Fe2+ → Fe3+ + OH + OH- Nitric oxide (ONOO-) Reactions relevant to ROSinduced cell injury  Lipid peroxidation of membranes Oxidative damage is initiated when the double bonds in unsaturated fatty acids of membrane lipids are attacked by oxygen-derived free radicals  Oxidative modification of proteins oxidation of amino acid residue side chains, formation of protein-protein cross-linkages (e.g., disulfide bonds), and oxidation of the protein backbone, resulting in protein fragmentation  DNA damage: Reactions with thymine in nuclear and mitochondrial DNA produce single-stranded breaks in DNA Summary  Diagnosis of disease, laboratory, epidemiology & autopsy  Cell injury and death: concept and process  Mechanisms of cell injury: causes & main mechanisms of cell damage  Injury by ROS: oxidative modification of lipid; protein & DNA damage