Wk1- Ch. 1, 2, 4, 7 Pathophysiology PDF

Chapters 1, 2, 4, 7 Introduction to Pathophysiology Homeostasis & Adaptive Response to Stressors Cell Injury, Aging, and Death Neoplasia don't cover everything in-class so watch video....

Chapters 1, 2, 4, 7 Introduction to Pathophysiology Homeostasis & Adaptive Response to Stressors Cell Injury, Aging, and Death Neoplasia don't cover everything in-class so watch video. Introduction to Pathophysiology Chapter 1 About This Chapter Pathophysiology Health and Disease Disease Distribution What is pathophysiology? The study of the functions of the human body in the disease state /Pathologic State. Interrelated topics in pathophysiology: Etiology Pathogenesis Clinical manifestations Treatment implications What is pathophysiology? (cont.) Etiology caused the disease Whe Study of causes or reasons for a particular disease or injury Classifications: Idiopathic = Cause is unknown of ↳ think idiot, so idk consequences ~ Iatrogenic = Cause results from unintended or unwanted medical , Physician caused treatment Risk Factor: A factor that increases the likelihood of disease you'lldon't mean get it , it's just likelihood. Pathogenesis Development or evolution of disease, from initial stimulus to ultimate ↳ like flow chart expression of manifestations of the disease The step it. the ledto it or caused Description of how etiologic factors alter physiologic function and lead to clinical manifestations that are observed in a particular disorder/disease What is pathophysiology? (cont.) Clinical Manifestations Signs: objective or observed manifestation of disease measurable ex-BP ↳ ex-bruise Symptoms: subjective feeling of abnormality in the body ↳ ex-headache , lethargy Stages and Clinical Course Latent period: time between exposure of tissue to injurious agent and first appearance of S&S. Also refers to a period during an illness when S&S temporarily become mild, silent, or but you dut know disappears you yet So in. , Prodromal period: time during which first S&S appears, cres of flu. indicating onset of disease seeing · LB , it's like Acute phase: disease/illness reaches its full intensity ~ feeling at worst What is pathophysiology? (cont.) Stages and Clinical Course (cont.) Acute clinical course: short-lived; may have severe manifestations but shorter duration Chronic clinical course: may last months to years, sometimes following an acute course Exacerbation: a sudden increase in severity of disease or S&S Remission: decrease in severity, signs, or symptoms; may indicate disease is cured Convalescence: stage of recovery after a disease, injury, or surgical procedure S Pathophysiology Question Which of the following is an example of the clinical manifestation known as a sign? A. Nausea ~ B. Bruise C. Headache D. Loss of appetite What is pathophysiology? (cont.) Want to consider patient/individual in nursing , this class is general. Treatment Implications Understanding the etiology, pathogenesis, and clinical consequences of a particular disorder/disease/illness may just w/ses you ant want to deal determine which treatments could be helpfulS go but cause , treat cause , ses an+ just put a bandaid on it. away. Most pathophysiology textbooks focus on general treatment implications rather than specifics Concepts of Normality in Health and Disease Individual Factors: Cultural considerations: each culture defines health and illness in a manner that reflects their experience Age differences: a normal value at one age may not be normal at age 20s vs Old another age (X: infant vs.. Gender differences: a normal value for men may not be normal for women or vise versa qVS of ex.. Other Factors: Situational differences: determine whether a derivation from normal is abnormal or an adaptation mechanism just stay shid be looked So the whole at , not values. Time variations: may impact how the body responds from day to night, or at varying times (circadian rhythm) Factors Affecting Patterns of Disease Distribution gomovie "Contagen" Concepts of Epidemiology Epidemiology: study of the patterns of disease involving populations; examining the occurrence, incidence, prevalence, transmission, and distribution of diseases in large groups of populations/people Types Endemic disease: native to a local region ↓ Epidemic disease: spread to many people at the same time & Now it's spreading , ↓ Pandemic disease: spread to large geographic areas eX-COVID-19 Factors Affecting Patterns of Disease Age, ethnic group, gender Socioeconomic factors/lifestyle considerations, geographic location Factors Affecting Patterns of Disease Distribution (cont.) Levels of Prevention Primary: altering susceptibility or reducing exposure for susceptible ↓ getting vaccines ex: immunizations flu other persons. altering your chance of getting the disease Preventitie. Secondary: early detection, screening, and management of disease detect to familynx manage it ex-yearly blood , work to check Alc level as of type I diabetes. LB a bit. Tertiary: rehabilitation, supportive care, reducing disability, and restoring effective functioning ↳ trying to get back to full help  Levels of Prevention Mr. BK is a 53-year-old man being seen in the primary care clinic. He tells you he went to a health fair and was told he had an elevated blood sugar. At his last visit it was also elevated and you find out his brother and mother have Type II diabetes. 1. When looking at the level of prevention, which level(s) would the health fair fall under: Primary, Secondary or Tertiary? ~ secondary Disease Prevention Question Which of the following is an example of primary prevention? ~ A. Maintaining routine immunizations B. Screening for cancer C. Rehabilitating after a stroke D. Performing monthly breast exams Homeostasis & Adaptive Response to Stressors Chapter 2 About This Chapter Homeostasis Stressors, risk factors, general adaptation response Types of stress and treatments What Is Homeostasis? healthy in homeostasis , when hot ,. illness Homeostasis is a state in which all symptoms are in balance at an ideal “set point” despite alterations within the body Homeostatic response: mechanistic, predictable series of orchestrated internal events basically help body go back homeostasis as way. to to in What type of parameters must be controlled? Osmolarity, temperature, pH Nutrients, water, Na+, Ca2+, oxygen, hormones What Is Allostasis? Takes Situation into consideration. Allostasis: ability to successfully adapt to challenges. A dynamic process that maintains or reestablishes homeostasis in light of environmental and ex-HR4 during exercise which you technically lifestyle changes. during exercise you dut want , , be low want to too. So it's an adaption That's healthy.. Homeostasis Review Circle the correct answers within each statement about control mechanisms of the human body: When David runs a mile, his muscles release heat, which causes his body temperature to increase. In efforts to return his temperature back to normal, his sweat glands are likely to ~ (increase, decrease) secretions, and blood vessels of his skin are ~ likely to (dilate, constrict). These mechanisms are examples of ~ (positive, negative) feedback control mechanisms because they - alter a parameter such as temperature in the (same, opposite) direction as it had originally been changed. Homeostasis Review Circle the correct answers within each statement about control mechanisms of the human body: ~ Most control systems of the body are (positive, negative). They ~ introduce (stability, instability) into a system. An example is ~ release of the pancreatic hormone insulin in response to (elevated, decreased) blood glucose level. The effect of insulin is to (raise, ~ lower) blood glucose level.  ↑ moderate stress ↳ happiest healthiest Stress & Risk Factors less productive Stressors are agents or conditions that can endanger homeostasis Physical, chemical, emotional, biological, social, or cultural Vary in scope, intensity, and duration When an external stressor disrupts homeostasis, illness may occur ↓ Feedback control systems adapt to changes to restore homeostasis We experience stress every day. In small doses, stress can be beneficial: Increases energy and alertness. Keeps us focused on the problem at hand When stress becomes too great it becomes a problem, damaging health, mood productivity, relationships, quality of life 5 makes you happier. Reactions to stress vary depending on genetics, gender, past experiences, cultural influences, developmental stage, and age RISK FACTORS: not stressors, but conditions or situations that increase the likelihood of encountering a stressor  According to Hans Selye’s General Adaptation 2 GAS Syndrome, the body reacts to stress in the following stages: Physical or psychological stressor Alarm Reaction gets body going dealw/stress 13tstep: to Arousal of CNS begins, flight-or-fight response, sympathetic NS involved Epinephrine, NE, and other hormones are released, causing an increase in HR, vasopressin cortisol & ex : , , etc. contractility, oxygen intake (respiratory rate), and mental activity everyone gets involved so. Resistance 2nd stage: Activity of the nervous and endocrine systems in an attempt to return to homeostasis Allostatic state: Refers to the activity of various systems in attempting to restore homeostasis Recovery Exhaustion Point where body can no longer return to homeostasis Allostatic overload: “cost” of body’s organs and tissues for an excessive or ineffectively regulated allostatic response Organ damage begins (onset of disease) maybe even death , General Adaptation Syndrome (cont.) Other responses Corticotropin-releasing hormone (CRH) production ~ causes rel of cortisol. Antidiuretic ~Vasopressin/ADH hormone release Sympathetic nervous system (SNS) activation and catecholamines (E and NE) Renin-angiotensin-aldosterone pathway activation IRAA) (increase BP, increase blood volume) Review Slide GAS (cont.): Neuroendocrine interactions in response to stress Stressful stimuli excite receptors which relay to the hypothalamus The stress response is then mediated by catecholamines (E, NE) and glucocorticoids (cortisol) 13 12 LB Stressors itself exhib + I stressors signs and change the internal symptoms environment of part of of the ↑ as a nurse, you the body change Want to deal. Not this With this - LB general adaption response has it's own I I general adaptation signs and response helps maintain symptoms of the normal function in spite general adaptation of the stressor response Signs = Objective evidence of disease perceived by the examiner (ex: labs, bleeding) Symptoms = Subjective evidence of disease perceived by the patient (ex: headache, back pain) General Adaptation Syndrome (cont.) Why is it important to know the general adaptation syndrome? When you see a client, they will not only exhibit signs and symptoms of the underlying disease but also of the So see ses of GAS aldisease b) GAS Therefore, you need to know what those signs and symptoms are because if you try to suppress the general adaptation syndrome, you may make the client worse by interfering with natural natural coping coping mechanisms mechanism GAS: Cortisol - The “Stress Hormone” Diverts metabolism from building tissues to Hypothalamus supply energy to deal with the stress CRH Corticotropic rel n. Primary glucocorticoid Anterior pituitary Promotes appetite and food-seeking adrenocorticotropin Causes signs & symptoms of chronic stress ACTH rel n.. Increased blood glucose, stronger sympathetic Adrenal cortex system effect on heart rate Decrease nonessential activities like: Cortisol Hormone production, metabolic rate, reproductive functions Alters glucose, Suppresses fat, and protein inflammatory Bone formation, red and white blood cell metabolism and immune production (immune system depression, responses anti-inflammatory effects) GAS: Antidiuretic Hormone (ADH) Also called vasopressin Causes vasoconstriction Makes kidneys reabsorb water from urine to blood  GAS: Sympathetic System - “Fight or Flight” Response Rapid response to trauma, emergency Pain, fear, low BP Epinephrine and norepinephrine released hypothalamus Both attach to adrenergic receptors SNS activated Norepinephrine: SNS neurons Causes vasoconstriction and raises BP Norepinephrine Reduces gastric secretions - adrenal medulla Increases night and far vision Epinephrine released into blood Epinephrine: Enhances myocardial contractility, ii) Heart Blood vessels increases HR and CO Causes bronchodilation Increases glucose release from the liver ↑ HR & Vasoconstrict skin, (glycogenolysis) Contractility gut, & kidney ↑ BP GAS: Renin-Angiotensin- Aldosterone Pathway Kidneys release Renin Activated by: Converts Angiotensinogen into Sympathetic system Angiotensin I Decreased blood flow to kidneys ACE ANG I: weak vasoconstriction Angiotensin II Angiotensin-converting enzyme (ACE) Adrenal Cortex ANG II: stronger vasoconstriction Aldosterone Also stimulates the adrenal cortex to Kidney release Aldosterone Aldosterone released Reabsorb Na+ and water Secrete K+ ↳ Na+/K+ ATPase in nephrons activated by.. 3 out , zin Kidneys reabsorb Na+ and H2O Increased blood volume and BP Kidneys secrete K+ GAS: Other Endorphins Endogenous opioids (body’s natural pain relievers) Raises pain threshold Produce sedation and euphoria Oxytocin Produced during childbirth and lactation Associated with bonding and social attachment Thought to moderate stress response and produce a calming effect Stress Review Use these words to answer the following questions: Alarm Exhaustion Resistance Arrange in correct sequence the 3 phases of the GAS: ~ Alarm, resistance alarm Resistance, - - Exhaustion exhaustion Which phase involves action of pituitary, sympathetic nerves, and ↑ adrenal medulla and cortex hormones? Alarm alarm In which phase does the body try to fight back? ~ Resistance resistance But if these mechanisms fail, then the stage of ___ (with possible ~ death) occurs. Exhaustion exhaustion GAS Review Which stage of the general adaptation syndrome facilitates the individual’s allostatic restoration of homeostasis? A. Alarm B. Resistance C. I Exhaustion D. Allostatic load  A woman is brought into the hospital after a motorcycle accident. She presents with: Increased heart rate Low blood pressure old be hemmoraging -. No urine production Dilated pupils No bowel sounds Elevated blood glucose Pale, sweaty skin What should be fixed first? Why? & Sympathetic NS Most of these signs and symptoms are caused by the GAS: ↑ HR, no urine, no bowel sounds, pale, sweaty skin, dilated pupils, and ↑ blood glucose. They indicate the body's attempt to deal with an emergency Once the emergency is dealt with, they should resolve on their own The GAS ↑ HR and caused vasoconstriction, so BP should be normal. The abnormal Low BP should be addressed If you What symptom ~addressed a sign of would the GAS you address instead, you first might and lower why? her BP even more IR[WBP WhTheAcasvenormitosiasosS · show Stress Review Match these parts of the brain with the stress-related functions: Cerebral cortex Hypothalamus Thalamus Limbic system Reticular activating system (RAS) Conveys sensory information about stressors to different parts of the brain: Hypothalmus ThalamusCerebral Cortex Thalmus "2 didn't trustself , , Facilitate mental alertness during stress: RAS RAS earcuses you ~ Involved primarily with emotional aspects of stress: Limbic Limbic Coordinate autonomic and endocrine response to stress: ~ Hypothal mus Hypothalamus Stress Can Affect the Immune System by… nonessential · supresses/depresses of as it considers Decreasing immune cell production in bone marro Decreasing thymus activity & maturation of T-cell Overall, stress and cortisol suppresses the immune system Type of Stress: 1) Physiologic Stress Stress-induced changes in body functions (Physicall Detected by body’s normal regulatory sensors The body alters function to restore normal balance When normal balance is restored, negative feedback stops the reaction Type of Stress: 2) Psychosocial Stress more Psychosocial stress refers to events of psychological or social origin which challenge homeostasis Adverse environments or life experiences (i.e., natural disasters, war, loss of job) fighting trends family issues , w/ , , etc. Position in a social hierarchy, isolation, discrimination Directly affects the CNS even though not physical. ↑ meaning It turns on the stress responses, even when the body’s internal sensors have not detected an imbalance Do the stress responses solve the person’s problem? NO. Type of Stress: 3) Acute Stress > - sudden onset, short duration. Acute stress response: Pounding headache, cold Moist skin, stiff neck Activate neural pathways that mediate: Arousal, alertness, focused attention, aggression For persons with limited coping abilities, acute stress response can by detrimental In some situations, acute arousal can be life threatening, physically immobilizing a person when movement would avert catastrophe (e.g., moving out of the way of a speeding car) but instead freeze. Acute Stress Which organs of the body would you expect to see damaged by acute stress? Why? Think of wht the GAS acts on, so organs... Ischemia llow blood supply) Skin, Skin GI Gl tract , tract, kidneys = sustained vasoconstriction , Kidney-sustained vasoconstriction causing The heart = O demand o supply exceeds causing ischemia. > · ↳overworking. The heart = O2 demand exceeds O2 supply Type of Stress: 4) Chronic Stress Chronic stress, or long-term stress Sympathetic activity and cortisol are elevated - even in acure Complications result from the reduced immune response more likely to get ill. Long-term exposure to stress can lead to serious health problems because it disrupts nearly every body system: ๏ Raise blood pressure ๏ Suppress the immune system ๏ Increase the risk of heart attack and stroke ๏ Contribute to infertility, speed up the aging process ๏ Can rewire the brain, increasing vulnerability to anxiety and depression example of Chronic stress: PTSD Is Characterized by 3 Types of Symptoms Post-traumatic stress disorder, a type of chronic stress Sympathetic system is activated Cortisol levels are decreased ~ usually in chronic ,it is. For our class a Clevated but not here Due to experiencing a potentially life-threatening event: war, hurricanes,. tsunamis, child abuse, etc. Less then half of people exposed to traumatic experiences suffer from PTSD 3 Symptoms of PTSD 1.Intrusion: Reexperiencing an event through “flashbacks - so intruding E can cause I 2.Avoidance: Emotional numbing, disrupt personal relationships, depression 3.Hyperarousal: Increased irritability, concentration difficulty, exaggerated startle reflex, increased vigilance and concern over safety Memory problems, sleep disturbances, excessive anxiety Stress Review Identify the pattern of stressors in each case as: Acute Chronic sustained Chronic intermittent Jamal, age 5, has had middle ear infections 4 times in the past 2 ~ years: Chronic Chronic intermittent Intermittent Joe, age 40, was diagnosed with amyotrophic lateral sclerosis (ALS, Lou Gehrig disease, a progressive neurodegeneration of motor neurons) at 37. He still speaks and swallows, but most of his body ~ is paralyzed: Chronic Chronic sustained Sustained Stephanie develops a respiratory infection that leads to pneumonia within the first few days after she begins attending day care during a ~ viral epidemic: Acute Acute Adaptation to Stress is Determined by: Physiologic Reserve = The ability of body systems to increase their differs indiv for each function given the need to adapt (i.e., heart rate) LB In class ex w/obesity have lower reserve , ↳ resting 70 Max -220 ~ 1200 - 70) , someone 20 age 200 130 bpm physiologic.. - reserve Someone extremely healthy have higher. ex-20 , so LB Greater physiologic reserve , better Time = Adaptation is more efficient when changes occur gradually. adaption instead of all once. Losing a liter of blood though chronic GI bleeding over a week has mild effect while a sudden hemorrhage causing a rapid loss will cause hypotension and shock Health Status = Physical and mental health determines physiologic and psychological reserves and is a strong determinant of the ability So someone who is to adapt already adapt sick wht as well as someone who is That's healthy someone who is sick is , why always getting sick , Age = Capacity to adapt is decreased with extremes of age (infants and elderly) 2 adapt These demo ant , as well. Adaptation to Stress (cont.) Genetic Endowment = Genetic variability In Africa, the gene for sickle cell anemia persists because it provides resistance to infection with the malaria parasite Hardiness = Individuals’ emotional reactions to stressful situations and their coping mechanisms adaptibility change ex: to Psychosocial Factors = Social support helps withstand stress Nutrition = Deficiency or excess of essential nutrients Influences enzymes, immune response, wound healing Obesity predisposes to atherosclerosis, hypertension eX'. Sleep-Wake Cycle = Sleep restores function, tissue regeneration for ex: Circadian rhythms affect function (hormone secretion, immune, LB physical and psychological function). int's why sleep is valuable Adaptation to Stress Review Circle the person who is likely to adapt better in each case. Then identify from the list the adaptation factor involved: Age Health status Psychosocial factors Timing of onset Timing of onset Loss of 25% of total blood volume in: Timing of onset Jeanette, by arterial hemorrhage within a period of 3 minutes Irma, by bleeding from a peptic ulcer over the course of 3 months Prolonged diarrhea in: Age Aga Jamie, who is 2 months old Cassandra, who is 20 years old Treatments of Stress Disorders Avoid coping behaviors that impose a health risk ex: smoking drinking , , excessive eating ,. etc Instea d... Provide alternative strategies by consciously using higher brain centers to help control the sympathetic system's activity: Relaxation response - Sit quietly in a comfortable position, deeply relax muscles, breath with awareness, maintain positive attitude ·. very good for like yoga , meditation ,etc you Imagery - try to involve all senses to try to relax , ex-imagine beach Music therapy – reduce stress, pain, feelings of loneliness Massage therapy – relieve muscle tension Biofeedback – learn to control physiologic functioning by monitoring response to stress with immediate feedback (muscle tension with EMG, heat, sweat, etc.) ↳ 2x: ECh eX *  Mr. Smith had some “hard times” in the Army … But he “dealt with it” and has become a successful air traffic controller ↳ very stressful job , Mr. Smith is: 50 years old, overweight, has increased BP Has occasional tachycardia, insomnia, and GI discomfort High HR. He has had several colds already this year, and wants a flu shot What about his case might be stress-related?. All of it tech Answer Most of his conditions are stress-related Increased sympathetic activation could be contributing to his ↑ BP and HR, and GI discomfort Increased cortisol could be suppressing his immune system, leading to the frequent infections ↑ cortisol suggests chronic stress not PTSD. Cortisol levels are reduced in PTSD Is he suffering from PTSD? is not elevated his is No, be cortisol ,. bC keeps getting sick So high cortisol.  His Doctor Has Recommended Relaxation Therapy … CX : go do yoga meditate. , Mr. Smith is furious about this “new age gobbledygook”. How will you explain its physiological basis to him? Relaxation therapy is aimed at gaining control of the automatic stress responses, via hypothal to reduce mus the levels of epinephrine and cortisol in his bloodstream sosas can go away. Because the higher brain centers can activate sympathetic and parasympathetic systems, consciously manipulating the higher centers by meditation or visualization can help control the sympathetic system's activity If Mr. Smith is unable to believe this, he should try biofeedback biofeedback training, in which he would receive an objective indication of how well he had reduced the response from a sensor The way he can understand it works be motivated to keep going. General Adaptation Syndrome E paleness in skin ↓ urrne Production Renin-angiotensin-aldosterone system Create a flow chart showing how the following topics fit together in the renin- angiotensin-aldosterone system: Renin reacts with angiotensinogen to form angiotensin I Na+ and H2O reabsorbed Stimulates adrenal gland to secrete aldosterone Kidneys release renin into blood K+ secreted Increased blood volume Decreased blood flow to kidneys Angiotensin-converting enzyme in lungs converts angiotensin I to angiotensin II K+ loss Aldosterone activates Na+/K+ pump in distal tubules of nephrons Renin-angiotensin-aldosterone system decreased blood flow to kidmy gland to Stimulates adrenal gland to screre aldestrone Kidney rel Renin into. blood Ald activates Na+ /1 + pump in. distal tubules of nephrons. Renin reacts w/ angiotensinogen to form angiotensin 1. Na+ EHy0 K"secreted. reabsorbed ACE in lungs convert ang. I -ang 2. ↑ BV + 1053 Cell Injury, Aging, and Death Chapter 4 Content the comes up in future topics Baseline. , About This Chapter Reversible cell injury Cellular adaptation Irreversible cell injury Etiology of cell injury Cell aging Reversible Cell Injury upmost common ! Hydropic swelling: cellular swelling due to accumulation of water 1st manifestation of most forms of reversible cell injury Results from malfunction of Na+/K+ pump with accumulation of LB Sout , 2 in whelp intracellular Na+ & Since +20 from ATP swells. into cella. This wht causes it. goes follows , Any injury that results in loss of energy (ATP) will also result in swelling Characteristics: Large, pale cytoplasm Dilated ER Swollen mitochondria 3 organelles also swell. Cells in organs increase in size and weight Tncorgan itself. is doing this (T) Normal Cell Cell Swelling Reversible Cell Injury (cont.) Intracellular Accumulations: excess accumulations of substances ↳ good things or bad Leads to cellular injury due to: Toxicity Immune response Fatty Liver Taking up cellular space Characterized by accumulation of : Excessive amounts of normal intracellular substance Abnormal substances from faulty metabolism synthesis Particles that the cell is unable to degrade Common site of accumulation = Liver Cellular Adaptation Adaptive Cellular Responses in response to altered demand Smaller Ex-muscles after being. in cast get smaller. ~ sea less. Soused more bigger. - amut. ↑, size doesn't change & Nof something completly diff. LB. Cellular Adaptation (cont.) Atrophy = Cells shrink and reduce function used as much anymore muscic > not. ex : General causes: Decreased functional demand, disuse, denervation & nore longer attached to no Ischemia interrupt > blood flow to the part of more severe muscle for ex · body. Nutrient starvation Normal Interruption of endocrine signals Persistent cell injury Hypertrophy = Increase in cell mass and S augmented functional capacity Hypertrophy General cause: lopp of atrophys - Increased cellular protein content Increase functional demand n Lumen of ventricle now much smaller, Ch+ fill w/blood as well. Cellular Adaptation (cont.) Hyperplasia = Increase in functional capacity related to an increase in cell number due to mitotic division General causes = Increased physiologic demand, hormonal stimulation, persistent cell injury, chronic irritation of epithelial cells Metaplasia = Replacement of one differentiated cell type with another General causes = Adaptation to persistent injury, with replacement of a cell type that is better suited to tolerate injurious stimulation Fully reversible when injurious stimulation is removed Example - epithelial cells of airways due to cigarette smoke (columnar to squamous) Dysplasia = Disorganized appearance of cells because of abnormal variations in size, shape, and arrangement General causes: adaptive effort to persistent injury gone astray Significant potential to transform into cancerous cells (preneoplastic lesions) Irreversible Cell Injury roBF interruption Necrosis = Cell death, usually due to ischemia or toxic injury Necrosis occurs when the injury is too severe to cell starts So die. Local and systemic indicators of necrosis: Pain, elevated serum enzyme levels, inflammation (fever, increased WBC, malaise (feeling of discomfort, unease)), loss of function & tissue in the 4 types of tissue necrosis, depends on tissue type: know wht kind of fissues seen in to Coagulative (most common) = process begins with ischemia, ends with degradation of plasma membrane [heart] Liquefactive = liquification of lysosomal enzymes, formation of abscess or cyst from dissolved dead tissue [brain] Fat necrosis = Death of adipose tissue, appears as chalk white area, usually due to trauma or pancreatitis [pancreas] Caseous necrosis = characteristic of lung damage secondary to tuberculosis (bacterial infection), resembles clumpy cheese [lung] Irreversible Cell Injury (cont.) so larger Gangrene = Cellular death (necrosis) in a large area of tissue Results from interruption of blood supply to a part of the body Ischemia Dry Gangrene = Form of coagulative necrosis characterized by blackened, dry, wrinkled tissue separated by a line of demarcation from healthy tissue Wet Gangrene = Form of liquefactive necrosis, typically found in internal organs, can be rapidly fatal Gas Gangrene = Results from infection of necrotic tissue by anaerobic bacteria (Clostridium), characterized by formation of gas bubbles in damaged muscle tissue, can be rapidly fatal Irreversible Cell Injury (cont.) can be namal Gabnormal , Apoptosis = Programmed cell death Normal Process- LB Can occur in response to injury that does not directly kill the cell. The severe cell damage increases p53, a protein that triggers the cell’s own death to contain iniuy Activates a cellular suicide response Sacrifices self else. away from everything Not always a pathologic process Does not cause inflammation Etiology of Cellular Injury What causes it ? Ischemia = Interruption in blood flow Ischemia causes tissue hypoxia (low oxygen in tissues) ↓ me Results in power failure in the cell Due to lack of 11 believe aerobic energy Ischemia is the most common cause of cell injury and injures cells as lack of BF is less of nutments a waste faster than hypoxia alone Combination of disruption of oxygen supply with accumulation of metabolic waste (lactic acidosis) causing cell dysfunction Ischemic injury can be reversible but not after plasma, It caught early mitochondrial, and lysosomal membranes are critically damaged Etiology of Cellular Injury (cont.) Nutritional Injury = Not having adequate amounts of fats, carbohydrates, proteins, vitamins, and minerals which are essential for normal cellular function Nutritional deficiency may result from: Poor intake Altered absorption in G1 tract - blood Impaired distribution by circulatory system ex: blockage in BV. Inefficient cellular uptake Common causes of malnutrition: Poverty Chronic alcoholism Acute/chronic illness Self-imposed dietary restrictions Malabsorption syndromes Etiology of Cellular Injury (cont.) Infectious and Immunologic Injury = Bacteria and viruses Added injury may occur indirectly by triggering body’s immune response Chemical Injury = Toxic chemicals or poisons Physical and Mechanical Injury = Extremes in temperature Abrupt changes in atmospheric pressure Mechanical deformation Electricity Ionizing radiation  S Cellular Aging Cellular Basis of Aging = Cumulative result from: Progressive decline in proliferation and reparative capacity of cells Basically cells no longer ableto repairs & Exposure to environmental factors Mechanism of aging DNA damage causes aging happen to. Reduced proliferative capacity of stem cells Accumulation of metabolic damage Strands of DNA at ↓ the endof chromosomes Theories of aging Programmed senescene theory bel. natural process already part of DNA. Free radial theory when you > - free e-causes arand trying to steal e- copy you dnt antioxidants , whichis why so good Physiologic changes of aging. copy all of telomere Age-related decrease in functional reserve Inability to adapt to environmental demand When you un out, no Y longer can basically aged out. Cellular Aging Review A patient who is 85 years old reports to a health care provider every year for a flu shot. This is an important preventive intervention because: A. telomeres increase with age. B. immune and respiratory reserves decline with age. C. rigor mortis can lead to somatic death and aging. D. radiation sickness can make the flu and aging worse. Neoplasia Chapter 7 About This Chapter Cancer Epidemiology Risk factors Classifications Cell cycle Genetic mechanism of cancer Benign vs. malignant tumors Manifestations of cancer Cancer Cancer cells first develop from a mutation in a single cell that grows (proliferates) without the control that characterizes normal The issrecomes wome cell growth, do not die off (apoptosis) to keep the number of cells constant, and may spread to other sites (metastasis) test agressive it Neoplasia means “new growth” and implies abnormality of cellular growth. Can refer to both benign and malignant growth. Tumor refers to a mass. Can be both benign or malignant I Malignant tumor is cancer Benign tumor is generally easily cured Epidemiology Cancer is the 2nd leading cause of death in the US, only to cardiovascular disease Most cancer deaths occur in individuals over the age of 55 Men have a 1:2 and women and 1:3 risk of developing cancer obvi , can happen to kids , 5-year survival rate: 66% varys on kind Where. Survival rates can be 4 Early screening aids in early detection and prognosis 1/3 of cancer deaths may be attributable to lifestyle factors: Tobacco use, nutrition (high-fat, alcohol), obesity, sun exposure (UV ↳ smoking rays, skin cancer), sexual exposure to HPV (cervical cancer) Additional risk factors: eX : Viruses, radiation exposure, chemicals (asbestos), compromised immune system, genes, hormones wht be able to fight off abnormal cells. Risk Factors Tobacco use - death rate from lung cancer has increased (may be directly related to smoking) Lung cancer has the worst survival rate Also linked to pancreatic, kidney, bladder, mouth, esophageal, and cervical cancer Classification Cancers are classified by the tissue or cells it originates from: so where/origin Epithelial tissue – carcinomas Glandular tissue – adenocarcinomas Connective, muscle, and bone tissue – sarcomas Brain tissue, spinal cord – gliomas Pigment cells – melanomas Plasma cells – myelomas Lymphatic tissues – lymphomas Leukocytes – leukemia Erythrocytes - erythroleukemia The Cell Cycle and Growth Factor Receptors 2X: Pretend Breast issue Normally, the # of cells produced = the # material Nucleus carries of cells that die, thus the total number of to create. anything cells in the body remain constant estrogen so ~ Cells divide only when they are told to do so by growth factors which cause stable cells to enter the cell cycle and divide Growth factors attach to receptors and often work by affecting G proteins turning on enzymes and second messengers to signal the cell to divide. & end resultprocess Normal btw This cell is ready to respond to growth factors from another cell estrogen recepta E LB , go back Genetic Mechanisms of Cancer Carcinogen - Potential cancer-causing agent the can cause mutation. abt likelihood ) the more ↳ of Cancer i exposure don't mean you'll get it , all you're exposed to , < risk. So. Proto-oncogene - the normal genes that code for normal proteins Normal f things/grath ↓ LD LB used in cell division ' for normal things Growth factors Growth factor receptors Cytoplasmic signaling molecules (G proteins, enzymes that produce second messengers) Nuclear transcription factors Genes that turn the production of these proteins on and off Genetic Mechanisms of Cancer (cont.) Not normal i Oncogenes are mutated proto-oncogenes (introduced by a retrovirus, lost/damaged DNA sequence, error in replication) Cancer-causing gene. They still code for the proteins needed for cell division, but they might produce... Ibasically smthng goes wrong mutated) words how mutation as it's. In other , effects proto-oncogenes. Too much of the protein as it turns it on. An abnormal protein Inot working as it shid) Protein that turns on all by itself instead of smthing else causing it Protein that is made when it is not needed in thet cell Protein that cannot turn cell division off Protein that should be made by a different cell Genetic Mechanisms of Cancer (cont.) codes forr... & like quality-control ~ every step of the way. Tumor suppressor gene form checkpoint tumor-suppressor proteins formation of tumors that usually stop division of mutated cells stopping supresses by so cell division if it notices mutations. They keep most mutations from developing into cancer Include: cyclins, cyclin-dependent kinases Low activity or mutations of these genes lead to more cancers So the more you have of this gene , less risk of cancer. Cyclins make sure the cell has Cyclins measure made the proteins needed to whether the cell separate the chromosomes has grown large enough to divide Cyclins check that the DNA has been correctly duplicated  This Cell Has Been Infected with a Cancer-Causing Virus ↳ so it turns on proto-ocogene the codes for growth factors shid be off , , causing this to be ocogene factors when it shidnt & also make growth. What has changed?g How could it promote 1. uncontrolled cell division? What oncogene is to blame? This cell is not only making growth factor receptors but also its own growth factors It is stimulating itself to grow. It is stimulating itself to grow! Growth factor The oncogene could be a modified receptor gene for the growth factor or a modified gene that controls the activity of the Growth growth factor gene factors  If You Want to Stop This Cell from Dividing, What Should You Do? Give a drug that stop other cells from making the growth factor? effect be No diff l. cell making Not much effect because the cell is the itself is , at the site. making growth factors itself Give a drug that block growth factor receptors? Potentially old growth factor this cell is Could work. It prevents the growth work , prevents the making from attaching to its receptors. factor this cell is making from attaching to its receptors Give a drug that inactivates growth factors in the extracellular fluid? Growth factor is rel in ECF May Inactivate factor cld work.The Could growth work. The growth factortois ,. growth factor before binds it receptor towas prevent. A receptor released into the ECF. May inactivate the growth stimuli. growth factor before it binds receptors Growth factors eCf  Here’s Another Cell with the Same Cancer – but slightly diff. GFEGF receptor made in same part of Golgi Would Any of These Treatments Work?. A drug that stopped other cells from making the growth factor? No same reason , ((Baft shrinking?I ↳ (GF) as last slide. A drug that blocked the growth factor receptors? NO bC GF already receptor being. binded to rel , A drug that inactivated growth factors in the extracellular fluid? No baclastarea a turned on This cell is creating growth factors and receptors in the same part of the ER, so they attach and stimulate growth before they are released from the cell. No treatment affecting ECF growth factor or it's receptors No treatment growth affecting extracellular will affect this cells , growth factors or cell surface receptors will affect this cell's growth LB abt KeY GLOCK ,  Development of Cancer is f Multistep Nature of Carcinogenesis Initiation: initial mutation occurs Promotion: mutated cells are stimulated to divide Progression: tumor cells compete with one another and & for resources Start to sees Es as a develop more mutations result , it's manifestations. which make them more aggressive  LB S go back , helpful, Any Cell Can Mutate, But … In normal cells, “grown-up” cells are called differentiated because they are different from one another Before sell · , stem. 3 When undifferentiated, rapidly * early ↳ so on dividing cells mutate, they. form rapidly dividing tumors - malignant tumors Sobe likely more & ex: col breatti ↳ ~ making unditshaventomewhat there supposedta , mutation has more influence/power More agressived makes. & When differentiated, “working” cells mutate, they form differentiated “working” tumors - benign tumors not as bad , tend to 2 - - not mastisized.. "This is be cells the have differentiated have become morelikethece theresupposedtobe ,soatsompoint ot This So.... Benign Tumors be happens in ~ differented cells Cells look like normal tissue cells May perform the normal function of the tissue (like secreting hormones) This may lead to oversecretion Usually have a capsule around them ↓so... Usually do not invade neighboring tissues But they can damage nearby organs by compressing them · It's still a growth/mass so... Malignant Tumors phappens earlier Cells do not look like normal adult cells Malignant Lung where not differented. Do not perform normal functions of the organ Tumor Invades May secrete hormones of other tissues - Surrounding eX : now will Progesterore Tissues rel. No clear boundaries and send “legs” out into surrounding tissue (word cancer means “crab” and is based on these crablike legs)Get legs dnt go hard and as cancer rid of , let , to Divide rapidly, so: Tumors grow quickly Mutate faster and can change type ↳ so within the growth , they're not going to be the same type of cell. Can compress and/or destroy surrounding tissues ↳ likebenign. Commonly produce telomerase (an enzyme that repairs telomeres and may be a key for attaining immortality) divide forever > - get so allows it to shorter. telomeres as ant Metastasis – process by which cancer cells escape their tissue of origin and initiate new colonies of cancer in distant sites I Cells in a primary tumor develop the ability to escape and travel in the blood often - whthappens Metastasis occurs in 3 ways: Circulation through the circulatory and lymphatic system Accidental transplantation during surgery Spreading to adjacent organs and tissues Imagine you were a cancer cell. What abilities would you need to survive in the tumor? Tumor cells need to deal with crowding, competition for food and O2, and ) ↳ things rypical needs all the cells need waste products of other tumor cells. There is active competition within the. tumor, and the toughest, most aggressive cells are selected. Growth will be limited if they can't attract a blood supply by releasing angiogenesis factors What abilities would you need to metastasize? To metastasize, a cell must be able to move, eat a hole in the blood vessel, survive against turbulence, high O2 levels and predatory WBCs It must stop itself in the capillaries, eat a hole in the wall, and get out into the new tissue, divide in the new conditions and fight off the WBCs in the new tissue. Very few cells succeed in metastasizing! ↳ which is why it's strongest cells as survival of the fitest. Tammy Has Liver Cancer … Her doctor did an initial molecular diagnosis and put her on targeted therapy; the tumor shrank by almost 75% Two years later the tumor was growing again, and this time it did not respond to the drug Last year she was diagnosed with metastases in her femur that has not responded to the drug either ↳ same drug Tammy wants to know why the cancer cells stopped responding. Are they not all the same cells? which is whatever the remained Not same cell as maligent tumor tend to grow mutate Tumor cells are prone to mutate, so there are often a wide range of , did Only after 75 %. remaining resistant cells are to treatment. cells; chemotherapy selected for cells that resisted treatment When the tumor regrew, it contained more of the resistant cells She needs a new treatment. ~ LB ab+ wht she wants Warning Signs of Warning Signs of Cancer CAUTION Cancer in Children CHILDREN Change in bowel or bladder habits Continued, unexplained as kids weight loss ↳ as they suld be growing , A sore that does not heal consistent Headaches with vomiting in the morning Unusual bleeding or discharge Increased swelling or persistent pain in Thickening or lump in breast or bones or joints elsewhere Lump or mass in abdomen, neck, or Indigestion or difficulty swallowing elsewhere Obvious change in wart or mole Development of whitish appearance in pupil of the eye Nagging cough or hoarseness Recurrent fevers not caused by infections Excessive bleeding or bruising Noticeable paleness or prolonged tiredness 71 Manifestations of Cancer 1. Changes in organ function Not functioning as it shid ex-breast tissue making. Cortisol , Organ damage, inflammation, failure Benign tumors may overproduce normal organ secretions Malignant tumors may cause overproduction, but more commonly decreases production of normal organ secretions starts producing random · normone. 2. Nonspecific signs of tissue breakdown - this why some get smaller skinner. Protein wasting, bone breakdown 3. Paraneoplastic syndrome Consequences of hormones being secreted by tumor cells. Ex-producing too much thyroid H.The results of the rel is #3 ↳ so change in organ function.. 4. Bone marrow suppression Contributes to anemia, leukopenia (low WBC), and thrombocytopenia (low platelets) Manifestations of Cancer 4. Local effects of tumor growth & neighboring +issue. Bleeding Compression of blood vessels /crush Compression of lymph vessels (edema) Compression of hollow organs (i.e., GI obstruction) Compression of nerves (pain, paralysis) causes 5. Cancer cachexia syndrome include Weight loss, generalized weakness, increased metabolic rate Loss of appetite (anorexia), nausea/vomiting 6. Pain 7. Immune system suppression pairs W/#4 Worksheet 5 - Oncogenesis A woman has breast cancer. The doctor found the cells have very high levels of estrogen receptors. What proto-oncogene do you think was mutated in this cancer? ↳ growth facta The activator or repressor gene(s) for estrogen receptors How could the mutated proto-oncogene have caused the cells to grow? Estrogen is a breast tissue growth stimulator; ↑ estrogen receptors will ↑ the growth more to bind to signal How would each of the following therapies work on this cancer? (a) Tamoxifen (an antiestrogen drug) By ↓ estrogen, it would ↓ the growth signal (b) An antibody to the tumor cells with a toxin attached to it The antibody would provide targeted delivery of the toxin to the tumor cells target therapy (c) Lumpectomy followed by local radiation makes sure you dut miss anything Locala radiation Lumpectomy would remove the cells. After , causes lethal mutations in cells in the S and M phases of the cell cycle; rapidly dividing cancer cells are more often in these phases and thus more vulnerable radiation Chemo target cell in process of ↳ to the radiation dividing(tht's why side effectsl Chemo is systemic ,. rad is localized..  LB Worksheet 5 - Oncogenesis A second woman has breast cancer, but her tumor cells have normal levels of estrogen receptors. Instead, they have G proteins that are constantly active, ↳ soalways telling cell to grow producing high levels of the cyclic AMP. How could this cause the cells to grow?. cAMP, a second messenger, may turn on enzymes inside the cell, causing cell division to occur whether the cell is stimulated or not Which of the three treatments in the previous slide (Tamoxifen-an antiestrogen drug, antibody to the tumor cells with a toxin attached to it, or lumpectomy followed by local radiation) probably would not work well for this client? Why? Tamoxifen. This client’s problem doesn’t seem to be increased activity of estrogen receptors, so ↓ estrogen may have no effect  Chapter 1 Summary Etiology, pathogenesis, treatment Levels of prevention (primary, example: vaccination (secondary, example: regular exams) (tertiary, example: counseling on medications) Stages of disease (latent, prodromal, acute, chronic, exacerbation, remission, convalescence) Epidemiology (endemic, epidemic, pandemic)  Chapter 2 Summary Homeostasis, allostasis GAS stress response (stages, hormones, nervous system, norepinephrine) Factors that determine how we adapt to stress Treatments of stress disorders  Chapter 4 Summary Etiology of cell injury (ischemia, nutritional, infection, chemical, physical) Reversible cell injury (hydropic swelling, intracellular accumulation) Cellular adaptation (atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia) Irreversible cell injury (apoptosis, necrosis – coagulative, liquefactive, fat, caseous)  Chapter 7 Summary Cancer classification, primary (original location) vs. secondary (where it spread to) Carcinogen, proto-oncogene, tumor suppressor genes Cellular differentiation (malignant vs. benign) Tumor markers (produced by normal cells, helps determine cancer origin, helps identify progression of cancer, may be released into the blood) Cancer manifestations Malignant vs. benign Cancer treatment, chemotherapy, chemotherapy side effects (anemia, nausea, bleeding, infection)