Bio 4311 Basic Concepts of Disease PDF

Bio 4311 Basic Concepts of Disease  Disease » any deviation from or interruption of the normal structure or function of a part, organ or system of body Pathology (patho ‐ Greek for disease) » study Definitions of structural and functional c...

Bio 4311 Basic Concepts of Disease  Disease » any deviation from or interruption of the normal structure or function of a part, organ or system of body Pathology (patho ‐ Greek for disease) » study Definitions of structural and functional changes in: cells, tissues, and organs of the body that cause or are caused by disease Pathophysiology deals with the changes in body function caused by disease  Defined as a cause of disease Biological agents: bacteria, virus Definitions etc. Etiology: Physical forces: trauma (wound, injury), burns, radiation etc. Chemical agents: poisons, alcohol, toxins etc. Nutritional excesses and deficits Etiology Disease causing agents are nonspecific and many different agents can cause disease of a single organ A single agent/event can lead to multi organ disease Most disease states have multiple causes Multiple factors may predispose you to a particular disease (risk factors) Combination of genes and environmental factors may lead to disease (and don’t forget stress!!) Diseases of unknown cause are “idiopathic”  how the disease process develops and evolves Definitions Pathogenesis: sequence of cellular and tissue events that take place from time of initial contact with an etiologic agent until the ultimate expression of a disease Definitions Clinical Manifestations: manifestations are the signs and symptoms of a disease Symptoms: subjective complaint that is noted by a person with a disorder e.g. pain, difficulty breathing Sign: a manifestation that is noted by an observer e.g. elevated temperature, a swollen extremity  Acute Definitions Evolution of a Subacute disease Chronic  Epidemiology is the study of disease in populations looks at patterns, such as race, age, dietary habits, lifestyle, or geographic location of persons affected Definitions with a particular disorder e.g. determining whether cardiovascular disease is caused by smoking and whether risk Epidemiology: of heart disease decreases when smoking ceases determines how a disease spreads, how to control it, how to prevent it and how to eliminate it Definitions WHO – World Health Organisation The WHO is the directing and coordinating authority for health within the United Nations system. It is responsible for providing leadership on global health matters, shaping the health research agenda, setting norms and standards, articulating evidence-based policy options, providing technical support to countries and monitoring and assessing health trends. Study questions Who is the WHO? How does a disease evolve? What are the three stages? Do they happen in order usually? What is epidemiology? What does it study? Describe two examples of epidemiology What is the difference between a sign and a symptom? Which one would high blood pressure be? What about when someone says they have heart palpitations? What is the etiology of a nut allergy? BASIC CONCEPTS OF DISEASE I. CELL ADAPTATION II. CELL INJURY III. MECHANISMS OF CELL INJURY IV. CELL DEATH Cellular Adaptation cells have the ability to adapt when faced with stresses that when homeostasis is not endanger its normal structure achieved, disease occurs and function; this adaptation assists cells to survive and maintain function there are limits to cellular a cell can return to its adaptation; if faced with pre‐adaptive state once the overwhelming stresses, a cell signal for adaptation is may become injured or even removed die adaptive changes can be normal or abnormal depending on whether the response was mediated by an appropriate or inappropriate stimulus Types of adaptation Change in size Change in cell number Change in cell type Change in size, shape and organization (dysplasia) Intercellular accumulations and abnormal storage of products Cellular adaptation Cellular adaptation Hypertrophy: refers to an increase in cell size; leads to an increase in functioning tissue mass due to an increased workload‐ e.g. skeletal and cardiac muscle tissue the increase in cell size involves an increase in cellular components needed to help cell adapt to work demands with muscle cells, more actin, myosin and enzymes are produced exercise can lead to normal physiologic hypertrophy disease conditions can lead to pathologic hypertrophy there is a limit to hypertrophy whereby further increase in tissue mass can no longer compensate for increased demands Cellular adaptation Hyperplasia: refers to an increase in number of cells in an organ or tissue only occurs in tissues with cells that are still able to divide (mitotic) e.g. epidermal cells, glandular cells, intestinal epithelium hormonal hyperplasia – breast and uterine enlargement during pregnancy are due to estrogen stimulation compensatory hyperplasia – the regeneration of the liver after partial removal pathologic hyperplasia – excessive estrogen production can lead to endometrial hyperplasia and abnormal menstrual bleeding Cellular adaptation Metaplasia: a reversible change in which one adult cell type is replaced by another adult cell type. change in cell type occurs within same primary tissue group (e.g. epithelial vs connective tissue) possible reprogramming of undifferentiated stem cells that are present in the tissue undergoing the metaplastic changes usually a response to chronic irritation and inflammation and allows for substitution of cells that are better able to survive the conditions  example of pathologic metaplasia – change from ciliated columnar epithelium to stratified squamous epithelium in the airways of a Metaplasia smoker examples example of physiologic metaplasia – during inflammatory response, monocytes (WBC) moves to injured area and transforms into macrophages Cellular adaptation Dysplasia: deranged cell growth that leads to changes in size, shape and appearance some dysplasia can appear due to chronic irritation or inflammation this adaptation serves no specific function can be reversible if irritating stimulus is removed it is thought to be a precursor to cancer Cellular adaptation Intracellular Accumulations: represent a buildup of substances that cells cannot immediately use or dispose of, may include normal body substances – lipids, carbohydrates, bilirubin – that are present in abnormal amounts abnormal endogenous products, such as those resulting from inborn errors of metabolism exogenous products, such as environmental agents and pigments that cannot be broken down by the cell Cell Injury physical agents ‐ mechanical This can occur in a variety of ionizing radiation (gamma rays, forces, temperature extremes, ways mainly: xrays), and electrical forces free radical injury or hypoxia ultraviolet radiation (bring on radiation –> the suntan), Depends on the duration and intensity of the agent, to determine if there is an injury chemical agents – drugs, lead nonionizing radiation (heat, to the cell (reversible damage) toxicity, light, radio waves) or death of the cell (irreversible damage): biological agents – viruses, bacteria, fungi, protozoa nutritional imbalances – due to hypoxia, ischemia, malnutrition  MECHANISMS OF CELL INJURY Free radical injury: free radicals are highly reactive chemical species that can lead to cell injury reacting with key cellular components or setting off chain reactions leading to widespread damage ∗ high reactivity is due to unpaired electron reactions can lead to damage of cell membranes, cross‐linking of proteins, inactivation of enzyme systems, or damage to the nucleic acids that make up DNA free radicals are formed during normal cellular reactions, including energy generation, breakdown of lipids and proteins and inflammatory processes Mechanisms of cell injury molecular oxygen is the most frequent source of free radicals normally, most cells have chemical mechanisms that protect them from free radicals Damage occurs when the cell is: deprived of oxygen, exposed to certain chemical agents, radiation or other injurious agents This Photo by Unknown Author is licensed under CC BY-ND Mechanisms of cell injury Protection against free radicals: Antioxidants (exogenous or endogenous) to block synthesis or inactivate. Includes vitamins C and E and beta‐carotene Enzymes to break down superoxide to peroxide  Mechanisms of cell injury Hypoxic Cell Injury: refers to cells suffering from a lack of oxygen which interrupts production of ATP well‐differentiated cells, such as in the brain and heart require large amounts of oxygen brain cells begin to undergo permanent damage after 4 to 6 minutes of oxygen interruption of ATP production will lead to ionic imbalances and cellular swelling deprivation due to the failure of the sodium/potassium pump, (an active transport pump **needs atp) Hypoxia can be due to an inadequate amount of cellular membranes (plasma membrane as well as those of organelles) will become oxygen in the air, respiratory disease, ischemia leaky, which will lead to loss of enzymes, other proteins, RNA (decreased blood flow to an organ) reversible if oxygenation is restored; however, if not restored the cell DIES Study questions How do cells get injured? Do they always die? What are the differences in hyperplasia, hypertrophy, atrophy, dysplasia, and metaplasia? Which ones possibly lead to cancer What can we do to protect our cells from injury?