PPY400-1 - Intro Processes of Human Disease I PDF

Welcome to PPY400! Processes of Human Disease I Seneca College BScN Program Winter 2025 PPY400 Winter 2025 Dr. David Anderson [email protected] Office: Room 1128 I can be available before and after class Office hours: email me and we’ll set up a time to...

Welcome to PPY400! Processes of Human Disease I Seneca College BScN Program Winter 2025 PPY400 Winter 2025 Dr. David Anderson [email protected] Office: Room 1128 I can be available before and after class Office hours: email me and we’ll set up a time to meet.  PPY400 Intro to human disease & fundamental principles of homeostatic mechanisms How alterations in homeostatic mechanisms can disrupt the human body. Cell injury, cell death, and wound healing Inflammation, Immunity and Infection Pain-mechanisms, theories, and bodily responses Fluids, Electrolytes, and Acid-Base Balance/Imbalances Stress and Disease GI Disorders Cardiovascular Disorders Respiratory Disorders Endocrine System Disorders Musculoskeletal Disorders Modes of Instruction 1 class per week, 4 hours per class All classes are lecture-style Lecture power points are posted on Blackboard under “Course Content” as units Lecture slides will be posted online before each class Please (optional) print off lecture slides before class so you can follow along as I talk. You can add notes and extra information during class Modes of Instruction Textbook: Hubert, R.J. & VanMeter, K.C. (2023). Gould’s pathophysiology for the health professions (7th ed.). Elsevier. We Class Content Weekly Preparation e k 1 Course introduction Chapter 1 and 5 Cell injury, cell death, and wound healing 2 Pain Chapter 4 Inflammation and Immunity Chapter 5 Wound Healing 3 Immune pathology Chapter 7 Introduction to Infection Chapter 6 Stress and disease Chapter 26 4 TEST 1 20% (weeks 1-3) Fluid, Electrolyte and acid/base Pathology (self study) Chapters 2 5 Gastrointestinal Disorders disorders of the alimentary canal and peritoneum Chapter 17 disorders of the gallbladder and pancreas 6 Cardiovascular Disorders atherosclerosis, PVD Chapter 12 Vascular disorders (HTN) 7 Cardiovascular Disorders Assignment Due CAD Chapter 12 ACS STUDY BREAK 8 TEST 2 20% (weeks 4-7) Cardiovascular Disorders HF Chapter 17 Arrhythmias, Venous Thrombosis, Pulmonary Embolism 9 Respiratory Disorders principles of respiratory dysfunction Chapter 13 Hypoxemia and Hypercapnia Respiratory Insufficiency and Failure 10 Respiratory Disorders Chapter 13 Asthma, COPD, Pneumonia 11 TEST #3 20% (Weeks 8-10) Endocrine Disorders Chapter 16 - Diabetes 12 Endocrine Disorders Chapter 16 - Thyroid and Adrenal disorders 13 Musculoskeletal Disorders Chapter 9 - Bone fractures - Rheumatoid Arthritis, Osteoarthritis - Ankylosing Spondylitis - Osteoporosis 14 TEST 4 20% (NOT COMPREHENSIVE)  Modes of Evaluation Test #1 20% Test #2 20% Test #3 20% Test #4 (not comprehensive) 20% Assignment 10% Quizzes 10% TOTAL 100% All tests are written on-campus, at the beginning of class. Quizzes may be online or in-class Promotion Note: a minimum grade of “C+” is required for promotion to PPY500. A “C+” is a final mark of at least 65%. If you have concerns or questions about your mark at any point during the term, please come talk to me! The earlier we try to fix the problem, the better. Hint to succeed: DO NOT MISS QUIZZES OR TESTS! If you miss a test, you will not be allowed a re-write unless you notify me BEFORE the date of the test No re-writes for quizzes Re-writes are very rare. If you miss a test, you will receive a mark of “0”. You must have acceptable documentation to support an absence for a test. This is serious, do not lose marks by simply missing an evaluation! More hints to succeed… Always attend class! A large amount of material is covered in each class. If you must miss class, make sure a classmate takes notes and collects any handouts for you Participate in class discussion Read your notes/textbook before class Ask questions More hints to succeed… Turn off cell phones!!! If you use a laptop…no FB, emails etc. Pay attention You can always have a coffee or snack, just take the garbage outside. Keep the communication lines open. Lecture #1 Cell Injury, Aging and Death Intro from Chapter 1 Chapter 5 Pathophysiology Pathophysiology is the study of abnormalities in physiologic functioning of living beings. Pathophysiology examines disturbances of normal mechanical, physical, and biochemical function; either caused by a disease or resulting from an abnormal syndrome or condition. includes 4 topics: etiology, pathogenesis, clinical manifestations, and treatment implications Pathophysiology 1) Etiology – the study of the causes or reasons for the disease -identification of causal factors that provoke a disease or injury Ex. The influenza virus is the etiological factor that causes the flu “idiopathic” – the causes of the condition are unknown “iatrogenic” – disease/condition was caused unintentionally by a medical treatment Etiology continued… Most disorders are a result of several different etiological factors Ex. Coronary heart disease is a result of an interaction of genetic predisposition, diet, smoking, hypertension, lifestyle etc. “Risk Factor” – if this etiological factor is present, the probability of disease development is increased Ex. Your risk for lung cancer development increases if you smoke. Pathophysiology 2) Pathogenesis – the development or evolution of a disease, from the initial stimulus to the ultimate expression of the disease manifestations. -the sequence of physiological events that occur in response to an etiological factor Ex. the progression from fat deposit to clogged artery in coronary heart disease is the pathogenesis of the disorder. Pathophysiology 3) Clinical Manifestations - indications that the disease exists in a person; the disease becomes evident. Ex. fever is a manifestation that indicates the presence of disease Some diseases manifest quietly, that is, they are silent at onset and are detected only after it is far advanced. Health care professionals look for signs and symptoms to determine if a disease has manifested Signs and Symptoms “Signs” – objective manifestations; observed through clinical examination or by biochemical analysis, diagnostic imaging, lab test etc. Ex. elevated temperature, swollen extremity, changes in pupil size. “Symptoms” – subjective feelings of an abnormality in the body; reported by the affected individual Ex. “pain”, “difficulty breathing”, “dizziness” Stages of Disease Latent/Incubation period – the interval between exposure of a tissue to an injurious agent and the first appearance of signs and symptoms Prodromal period – the appearance of the first signs and symptoms; onset of disease -symptoms are often nonspecific: headache, nausea, lack of appetite etc. Acute Phase – disease reaches full intensity; greatest severity of signs and symptoms Stages of Disease continued Silent or Latent Period – if signs and symptoms become mild or disappear during the course of disease Subclinical Stage – disease is well established but patient functions normally (may not know they are sick) “acute” – a condition with relatively severe manifestations but runs a short course (hours, days or a few weeks) “chronic” – condition lasts for months or years Stages of Disease Some diseases follow courses of alternating “exacerbations” and “remissions” “exacerbations” – sudden increase in severity of a disease or signs & symptoms “remissions” – a stop or decline in severity of signs and symptoms of a disease Convalescence – stage of recovery after a disease, injury, or surgical operation “sequela” is a subsequent pathological condition such as scarring or deformation; a “complication” is a new or separate process that arises secondary to the original disease Stages of Disease Pathophysiology 4) Treatment Implications – the etiology, pathogenesis, and clinical manifestations lead to the prescription of treatment that may help with signs and symptoms. Cells Review normal cell form (anatomy) and function (physiology) Gould’s p.546, ANP100 notes Especially:  Recall receptors and ligands  Recall cell transport mechanisms  Recall cell respiration Cell Metabolism Cell Injury, Aging and Death Disease processes are often presented in terms of whole-body effects; but it is ultimately the cells that are affected. Cancer affects multiple organ systems, but is the result of alterations in cell function. Therefore, we must understand the general characteristics of cellular injury, adaptation, aging and death. Cellular Adaptation and Transformation (3) Cells can adapt to their environment and stimuli in a number of ways: Atrophy: Decrease in cell size Hypertrophy: Increase in cell size Hyperplasia: Increase in cell number Dysplasia: Cells display increased mitosis, are varying sizes and shapes, and have large nuclei. They are considered pre-cancerous. Neoplasia: Cells are dividing out of control and have abnormal cell Cell Injury Reversible Cell Injury – if the cell change is mild or short lived; the cell withstands the assault and can return to normal activity Often a result of cellular swelling and the accumulation of excess substances within the cell “Hydropic Swelling” – cellular swelling due to the accumulation of water; usually a result of malfunction of the Na+/K+ pump. Hydropic Swelling Failure of the pump to remove sodium (Na+) from the cell means water accumulates inside the cell (water always follows sodium!) Hydropic swelling is characterized by large, pale cytoplasm, dilated ER, and swollen mitochondria Severe hydropic swelling leads to ruptured ER, forming large water-filled vacuoles The more hydropic cells in an organ = increased size and weight of that organ  “Intracellular Accumulations” – excess substances in cells; cause cellular damage if they are toxic, provoke immune responses, or generally occupy space needed for normal cell functions. Normal intracellular substances that tend to accumulate are lipids, carbohydrates, glycogen, and proteins; could be due to faulty metabolism or lack of enzymes, or due to genetics/disease processes. Fatty Liver The liver is a common site of intracellular lipid accumulation Fats are normally stored, metabolized and synthesized in the liver Excessive alcohol intake is often associated with fatty liver; thought to result from toxic effects of alcohol on liver cells and the preferential metabolism of alcohol instead of fat Fat-filled liver cells compress cellular components to one side and cause tissue to appear yellow and greasy; liver increases in size and weight Fatty Liver Large intracellular vacuoles of lipid in liver tissue http://www.elements4health.com Intracellular Accumulations continued Other common accumulated substances include: sorbital in neurons of diabetics, inorganic particles such as calcium and tar, mineral dusts such as iron, lead, and coal (common in lung tissue) Calcium deposits are common in the heart, blood vessels and eyes  causing obstruction Cellular Adaptation Cellular adaptation is a response to persistent, sub-lethal stress Reversible adaptive cell changes include; atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia These changes are reversible if the cellular stress is removed Atrophy Atrophy - cells decrease in size Can be a result of: 1) Disuse 2) Denervation 3) Ischemia (inadequate blood supply to tissue) 4) Nutrient starvation 5) Interruption of endocrine signals 6) Persistent cell injury 7) Aging  Atrophy Atrophy is the cell’s attempt to minimize its energy and nutrient consumption by decreasing intracellular organelles and other structures A decrease in functional demand can lead to “disuse atrophy”. Ex. If an extremity is immobilized in a cast, shrinkage of skeletal muscle can occur Tissue can return to normal size if activity is resumed Hypertrophy Hypertrophy is an increase in cell mass; response to increased physiologic or pathophysiologic demands Increase in size is typically due to the increase in cellular protein content Cells can return to normal size, but may not if changes to connective tissue structures is extensive For example, repeated exercise can increase skeletal muscle mass and strength = hypertrophy of individual muscle cells  Hypertrophy continued Negatively, some organs undergo unwanted stress causing them to hypertrophy; for example, hypertrophy of cardiac muscle cells due to hypertension. Hyperplasia Hyperplasia is an increase in the number of cells Usually a result of increased physiologic demands or hormonal stimulation; but is also due to persistent cell injury Liver enlargement is often a result of hyperplasia in response to drug detoxification and increased stress on the liver. Calluses and corns on the skin are an example of hyperplasia of epithelial cells! Chronic irritation causes mitotic division of cells to increase numbers!  Metaplasia Metaplasia is the replacement of one differentiated cell type with another Often a result of an adaptation to persistent injury; new cell type can handle the stress Most common: replacement of glandular epithelium with squamous epithelium In response to chronic irritation by smoke; ciliated columnar epithelium in the bronchial mucosa is changed to stratified squamous epithelium Reversible when harmful stimulus is removed Some cancers of the lung, cervix, stomach and bladder are thought to derive from metaplasic epithelium Dysplasia Dysplasia is disorganized growth; abnormal variations in size, shape and arrangement of cells Commonly seen in hyperplastic squamous epithelium (when cells are increasing in number) and in the intestine Dysplastic cells have great potential to transform into cancerous cells Seems to be an adaptive strategy gone wrong Dysplasia http://www.colposcopy.org.uk/ cervicalsmears.htm Irreversible Cell Injury Cellular death occurs when an injury is too severe or prolonged to allow cellular adaptation or repair Necrosis and Apoptosis are two processes that contribute to cell death Necrosis results from ischemia or toxic injury and is characterized by cell rupture, spilling of contents into ECF and inflammation Apoptosis is a response to injury that does not directly kill the cell, but triggers events that activate cell suicide. Necrosis Necrosis is “death and degradation of body cells or tissues in response to injurious events” Necrotic cells have shrunken nuclei, swollen cell volume, dispersed ribosomes, disrupted plasma and organelle membranes Once the plasma membrane is disrupted, the cell will die Copstead-Kirkhorn, L.C. & Banasik, J.L. (2009). Pathophysiology (4th ed.) Necrosis When cells die, their contents are released into the blood stream The appearance of certain intracellular enzymes in the blood tells the body which organ is damaged and to what extent The body responds with a general inflammatory response (general malaise, fever, increased heart rate, increased WBC count, and loss of appetite)  Types of Necrosis – depends on type of tissue affected 1. Coagulative – most common type; due to ischemic injury  loss of plasma membrane ability to keep electrochemical gradient  influx of calcium ions and mitochondrial dysfunction  breakdown of plasma membrane and nucleus -coagulative necrotic area is hard, solid and full of denatured proteins - Area is slowly dissolved by proteolytic enzymes  Types of Necrosis continued 2. Liquefactive – common in the brain; can be a result of bacterial infection -body will form an area of localized WBCs that will digest dead cells  liquid debris - Dissolution of dead cells occurs quickly in a liquefied area of lysosomal enzymes and dissolved tissue (abscess or cyst) http://library.med.utah.edu  Types of Necrosis 3. Fat necrosis – death of adipose tissue; usually a result from trauma or pancreatitis -activated digestive enzymes are released from pancreas or injured tissue -enzymes attack the cell membranes of fat cells  release triglycerides  convert to free fatty acids  form chalky white calcium chunks http://www.radswiki.net Types of Necrosis continued 4. Caseous – characteristic of lung tissue damaged by tuberculosis (TB) -areas of dead lung tissue are white, soft, fragile, clumpy and are walled off by WBCs -these clumps of necrotic debris may stay in the lung forever http://www.mevis-research.de Gangrene Cellular death involving a large area of tissue Usually results when blood supply is disrupted to a particular body part (toes, leg etc) Tissue will die without oxygen and become necrotic “dry gangrene” is a form of coagulative necrosis  tissue is black, dry and wrinkled “wet gangrene” is a form of liquefactive necrosis  typically found in internal organs (tissue looks black and often smells foul due to invasion of bacteria) Wet gangrene is life-threatening due to fast spread of tissue damage and toxin release into blood Gangrene continued “gas gangrene” is the formation of bubbles of gas in damaged muscle tissue  results from infected necrotic tissue by anaerobic bacteria  infection spreads rapidly Apoptosis If cells are no longer needed, they activate a cellular death pathway resulting in cell suicide Unlike necrosis, apoptosis is clean, tidy and does not cause inflammation Apoptosis is consistently occurring as tissues repair and remodel Apoptosis can also be pathological; for example, cell suicide is thought to be the major cause of tissue death following an MI Apoptosis is also a primary factor in diseases such as heart failure and dementia Apoptosis continued Apoptosis can be trigged by extrinsic signals; withdrawal of “survival” signals from neighbouring cells/fluid or activating of “death receptors” will activate the apoptotic pathway Intrinsic triggers, such as irreparable damage can cause a cell to cause its own death Neighbouring cells are prompted to ingest apoptotic cells because a phospholipid that is normally located on the outside of cells is flipped inside  this indicates the cells is dead and needs to be discarded Types of Cell Injury Living cells need a constant supply of oxygen to produce ATP Lack of oxygen is called hypoxia and results in power failure within the cell Tissue hypoxia is most often caused by ischemia (interruption of blood flow to an area) but can also be caused by heart failure, lung disease, and RBC disorders Ischemia is dangerous to cells because it not only disrupts blood supply, but also deprives the cell of nutrients and allows waste to build up ATP production will fail  Na+/K+ pump will fail  hydropic swelling Ischemia and Hypoxia: Cellular Energy Failure: Some cells are highly sensitive to oxygen deprivation because especially when ATP requirements are high and they have limited capacity for anaerobic metabolism during ischemia (ie: neurons) Mitochondrial dysfunction due to lack of cellular oxygen→ initiation of anaerobic glycolytic pathways; pyruvate converted to lactate; hydrogen ions → cellular acidosis; inadequate energy supply leads to deterioration of ion gradients  Na+, Ca2+ accumulate inside cell; Ca2+ overload injury Ischemia and Hypoxia (cont.) Excitatory Amino Acids: Glutamate Excessive glutamate may be released because of impaired membrane integrity  Reuptake mechanisms also fail to remove excess glutamate ~energy- dependent processes Excess glutamate stimulates nearby neurons that then take up large amounts of injurious Ca2+ ions → Ca2+ overload injury  Accompanying H20 inflow → neural swelling (cytotoxic edema) Glutamate also binds to NMDA receptors, stimulating nitric oxide (NO) production in neurons  excess NO may increase the production of reactive nitrogen species (free radicals) which damage cellular components Glutamate Normally glutamate binds with AMPA receptors to open Na+ channels (depolarization) at synapse ATP is required for re-uptake If glutamate is not removed, a second receptor is stimulated to open for Ca++ (water follows = cytotoxic edema/swelling) Increased IC Ca++ impairs mitochondrial function and produces increased nitric oxide (NO) leading to free radical production Ischemia and Hypoxia (cont.): Calcium Overload Injury The influx of Ca2+ ~ energy failure and glutamate is accompanied by mitochondrial energy failure which decreases mitochondrial ability to sequester Ca2+ → further Ca2+ overload and mitochondrial damage Excess intracellular Ca2+ activates an enzyme cascade → phospholipase activation, free radical formation and membrane damage → cell death (apoptosis) Reperfusion Injury Secondary injury When oxygen reenters cells, erratic transfer of electrons to oxygen can produce reactive oxygen products that behave as free radicals ◦ Resulting cell membrane damage yields more oxygen free radicals and mediators of inflammation Return of blood flow also brings inflammatory chemicals to area More types of cell injury Nutritional – adequate amounts of fats, carbs, proteins, vitamins and minerals are needed from the cells external environment Nutritional excesses are just as dangerous (toxic) as deficiencies Cells are also injured by bacteria and viruses Toxic chemicals and poisons Physical and mechanical forces: temperature, pressure, deformation, electricity, radiation etc. Cellular Aging and Death Cellular aging is the cumulative result of the decline in proliferative and reparative capabilities of the cells combined with exposure to environmental factors that cause damage to the cells The “programmed senescence theory” states that aging is the result of an internal genetic program; studies showed that cells taken from older individuals divided less frequently than cells from younger individuals The theory concludes that every cell can only replicate a finite number of times; thought to be because the cell chromosome (telomeres) shortens with each cell division until it becomes dormant or dies Read more in text Oxidative Stress The “free radical theory” states that cellular aging is a result of accumulated metabolic cell damage over time. The higher the cell’s metabolic rate, the greater the production of oxygen free radicals  cause damage to the cell membrane Also known as oxidative stress Oxidative Stress Oxidative stress is an imbalance of free radicals and antioxidants in the body, which can lead to cell and tissue damage. Oxidative stress occurs naturally and plays a role in the aging process. Free radicals, including reactive oxygen species, are molecules with one or more unpaired electron Antioxidants are substances that neutralize or remove free radicals. The neutralizing effect of antioxidants helps protect the body from oxidative stress. Wound Healing Goal is to restore damaged tissue 2 possibilities: REGENERATION or REPLACEMENT Tissue Regeneration:  Injured cells are replaced by same type  Little to no evidence of previous injury  Only possible when cells have capacity to undergo mitosis  Some cells undergo mitosis throughout lifespan – good repair: most epithelial tissues Some cells stop mitosis at maturity but with appropriate stimuli can undergo regeneration (some liver, muscle and nervous system cells) Some cells seem to have no capacity for mitosis under any circumstances: most neurons, cardiac muscle cells – leave scar tissue – no regeneration  The presence of an intact ECM ensures a complete repair: provides rigidity to bone, tension to soft tissues, growth factors, nutrients, adhesive glycoproteins to connect cells to the ECM, H2O, structural proteins etc. FIBROUS REPAIR: REPLACEMENT When: Injury is severe and/or ECM is unable to assist or cells affected are unable to undergo mitosis: Replacement occurs with c.t. = scar tissue 1. Mast cell degranulation: release histamine and other chemicals to signal injury and activate inflammation 2. Granulation tissue is formed: very vascular, innitially disorganized collection of capillaries and fibroblasts  ANGIOGENESIS: new blood vessels are formed from damaged blood vessels –new endothelial cells and smooth muscle cells are formed and organized at site of injury FIBROGENESIS: fibroblasts migrate to site and secrete ECM deposits to healing tissues SCAR TISSUE: builds on granulation tissue and matures with little vascularization Regulation of Healing Chemical mediators and growth factors  ie: histamine, prostaglandins, complement, clotting and kinin systems, immunoglobulins, IGF’s and more Two Roles: 1. chemoattractants – attract repair factors to site of injury 2. mitogens – increase the proliferation of cells in healing HEALING PROCESS 1st Goal: fill space and restore continuity Regeneration is ideal 1st Intention Healing: no loss of tissue – simple wounds (ie: incision) 2nd Intention Healing: loss of tissue –burns, larger wounds: increased possibility of infection, complications and loss of function 3 Phases of healing: Inflammation, Proliferation, Remodelling INFLAMMATORY PHASE Onset of Injury: hemostasis, blood clotting etc.  Then vasodilation, leaking of plasma and WBCs into damaged tissues  Cellular phase: removal of foreign bodies, angiogenesis and arrival of fibroblasts PROLIFERATIVE PHASE From 2-3 days to weeks in duration:  Fibroblast activity is main factor: deposit collagen, growth factors etc. for angiogenesis and cell proliferation: granulation tissue within 24-48 hrs.  Epithelialization: epith. Cells migrate, proliferate and differentiate to form new surface layer  peaks in 5-7 days and continues for 2-3 weeks REMODELLING PHASE After 3 weeks or so and can last more than 6 months Synthesis and lysis of collagen to increase organization and strength (not to 100%) 2nd intention healing leaves obvious scarring and often loss of function Factors Affecting Healing Nutrition: need adequate amounts of lipids, CHO, pro-, minerals and vitamins Vit. A: stim. Epithelialization, capillary formation, collagen sysnthesis Vit. C: promotes pro- and collagen synthesis Zinc: increases cell proliferation Bloodflow: supplies nutrients and factors, removes wastes  Age: young: gtr capacity for healing but reduced ability to resist infection  As we age: reduced ability to produce collagen (decreased fibroblast activity), decreased elasticity of tissues (fragile), more prone to chronic wounds, injury often because of other underlying disease (DM, CVD etc.) Stress: increased stress depresses inflammatory processes.