AO Nursing 3366: Mechanisms of Defense, Inflammation & Immune Function PDF

AO Nursing 3366 Pathologic Processes: Implications for Nursing REQUIRED READING DOCUMENT #3 Mechanisms of Defense: Inflammation and Immune Function and Disorders Instructions: 1. Read this entire RRD (Required Reading Document) and other documents mentioned. 2....

AO Nursing 3366 Pathologic Processes: Implications for Nursing REQUIRED READING DOCUMENT #3 Mechanisms of Defense: Inflammation and Immune Function and Disorders Instructions: 1. Read this entire RRD (Required Reading Document) and other documents mentioned. 2. Work on Assignment #3 and submit by designated deadline. Note about objectives /outcomes and studying for this course: For ALL content in this course, the student will be able to DESCRIBE/DISCUSS/IDENTIFY correlations (links) between pathophysiology of the disease and its clinical manifestations. In other words, #1: how does the pathophysiology of a particular disease cause the signs and symptoms, and #2: if a patient presents the signs and symptoms of a disease, be able to use critical thinking to figure out the disease process that is most likely in that context. Objectives /outcomes for this subject: DESCRIBE/DISCUSS/IDENTIFY: 1. basic aspects of 1st line of defense and effects of pathologies such as Sjogren’s syndrome. 2. Basic aspects of 2nd line of defense, including; normal inflammatory processes: role of mast cells; plasma protein acute phase reactants; biochemical mediators such as histamine, prostaglandins, leukotrienes, cytokines; clotting cascade; and phagocytes such as neutrophils and macrophages. relationship of above processes to acute local and systemic manifestations (such as sepsis); diagnostic tests such as CRP; and basic treatment modalities. disorders of hyper-inflammation such as septic shock and of hypo-inflammation, such as phagocyte and complement deficiencies. 3. Basic aspects of 3rd line of defense, including normal immunocyte processes, including roles of cell-mediated and humoral systems differences between active & passive immunity and their subcategories natural and artificial therapeutic / preventative measures such as vaccinations & immunoglobulin therapy immune deficiency disorders such as AIDS and the relationship of: o its epidemiological considerations, portal of entry and transmission prevention. o its pathophysiology, including mechanisms of action of its causative retrovirus, HIV. o diagnostic & monitoring tests, S&S, and basic treatment modalities. o opportunistic infections such as CMV retinitis, thrush, Pneumocystis Pneumonia (PCP), & Kaposi’s sarcoma, and their significance. hypersensitivities such as o allergic reactions, including anaphylaxis. o autoimmune processes such as Graves’ disease, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, Goodpasture’s, hemolytic reactions, Type I diabetes, multiple sclerosis, celiac disease o alloimmune reactions such as blood transfusions, Rh factor incompatibility of fetuses, histocompatibility OUTLINE I. Overview of Normal Defense Mechanisms A. General description of body’s defenses B. Innate (AKA “natural”) resistance C. Acquired (AKA “adaptive”) immunity II. First line of defense-- physical/mechanical and biochemical barriers & what can breach them A. Overview B. Skin and its glands C. Membranes / glands of body openings III. Second line of defense--NORMAL inflammatory process IV. Abnormalities of inflammation (ie, abnormalities in 2nd line of defense) A. “Not enough” inflammation B. “Too much” inflammation. C. Therapeutics for inflammation  V. Third line of defense—Normal immunocyte response VI. Abnormalities in immunocyte response (ie, abnormalities in 3 rd line of defense) A. Hypersensitivities—“too much” immunocyte response B. Immunodeficiencies—“not enough” immunocyte response I. Overview of body’s normal defense mechanisms A. General description of body’s defenses 1. an interaction and coordination of responses to stressors; ex of stressors: a. invasion by a foreign body, such as microbe, splinter, etc b. development of unnatural dangers, such as cancer cells. 2. the body’s defense systems in total is sometimes called “the immune system” which for clarity of learning can be split into the two big categories of innate resistance and acquired immunity. B. Innate (AKA “natural”) resistance-- the defense mechanisms we are born with; this includes: (Note: 1st line, 2nd line, and 3rd 1. 1st line of resistance (first defense against invasion)--body’s physical barriers, line defenses will which are immediate (response occurs at the time of contact with a stressor) be described and non-specific (the response process is the same, regardless of the type of separately, but in stressor). actuality these 2. 2nd line of resistance (secondary defense against invasion)-- inflammation, are closely interdependent.) which is also immediate and non-specific 3. innate category can also include states of resistance that are related to our species: human beings are naturally resistant to some infectious agents that cause illness in other species and vice versa: ex-- a. canine distemper cannot be “caught” by humans b. West Nile virus can infect birds, humans, horses, but not dogs or cats. C. Acquired (AKA “adaptive”) immunity-- 3rd line of defense 1. being able to resist certain diseases or conditions due to immunocyte immunocytes are lymphocytes involvement (B-cells & T-cells) 2. this type of response is delayed (response occurs later than the time of contact with a stressor) and specific (different immunocytes respond to different types of stressors). **************************************************************************************************** II. First line of defense--physical/mechanical and biochemical barriers & what can breach them A. Overview 1. part of innate resistance set of defensive responses-- includes skin & its glands, and membranes / glands of body openings 2. responds immediately & non-specifically to each stimulus 3. if a stressor breaches (breaks down) these defenses, 2nd & 3rd lines of defense are next in line to defend us. B. Skin and its glands 1. examples of defensive roles: a. protects more vulnerable areas underneath from simple environmental hazards b. desquamation of skin: shedding of skin cells = bacteria shed too c. various glands in skin secrete sweat, which has antibacterial & antifungal properties: 1) attack cell walls of certain bacteria.  2) contribute to making the skin actually acidic (ph 3 to 5), making it inhospitable to most bacteria. 2. stressors that can breach this defense-- lacerations, abrasions, punctures, etc C. Membranes / glands of body openings 1. eyes’ defense a. tears: blinking causes lacrimal glands to spread tears over eyes & the tears drain into lacrimal ducts, washing the eye regularly b. eyelashes c. stressors that can breach these defenses 1) dry eye syndrome—manufacturing of tears slows down; happens to some degree to almost everyone as they age 2) Sjogren’s syndrome—autoimmune disease that dries up all lubricating fluids in the body. 2. respiratory system defenses a. viscosity of mucus in nose plus hair traps bacteria (same with wax & hair in ears) b. cilia of cells in bronchi can “sweep” away foreign bodies c. cough reflex—if a foreign body is inhaled and reaches the carina, cough reflex stimulated. d. stressors that can breach these defenses: 1) cigarette smoking changes bronchial cells—no more cilia. (metaplasia) 2) cough reflex suppression such as in head injury or stroke. 3. gastrointestinal (GI) system defenses a. saliva contains protective enzymes b. stomach—HCl destroys most microbes c. gag reflex / vomiting gets rid of injurious agents such as harmful bacteria. d. bowels: 1) in the normal bowel are many “good flora” – microbes which do not harm us but do keep out malicious microbes by competing for food. 2) defecation: gets rid of injurious agents such as harmful bacteria. e. stressors that can breach these defenses: 1) Sjogren’s—dries up saliva, so less protection in mouth 2) anything that changes the bowel flora can leave us open to invading microbes; ex of something that might change the bowel flora- antibiotics can wipe out bowel flora. 4. genitourinary (GU) system defenses a. flow of urine washes away microbes b. vaginal secretions slightly acidic—kills bacteria. c. stressors that can breach these defenses 1) decreased urine flow, as in kidney stones or kidney failure 2) anything that changes vaginal acidity, such as douching  SEE CONCEPT MAP: NORMAL INFLAMMATION & IMMUNOCYTE RESPONSE, page 1 *****In order to understand diseases and disorders of inflammation & immunocyte response (2nd & 3rd lines of defense), you must completely understand the “norms” of inflammation & immunocyte response. Thoroughly read the following notes & the concept map “normal inflammation & immunocyte response” (also prep #4 as needed). *********************************************************************************************** III. Second line of defense-- NORMAL inflammatory process A. Process of normal inflammation 1. inflammation is a state of INNATE defense characterized by: a. being immediate and nonspecific (responds right away to every stressor in the same way) b. expected manifestations such as a certain (“normal”) degree of swelling, heat, erythema (redness), & pain. (SHEP) 2. inflammation is a normal, important body mechanism that helps us defend against stressors, begin the healing process, and call in the 3rd line of defense as needed: 3. because inflammation is an uncomfortable process it is often mistakenly thought of as an abnormal state. nomenclature—in many (but not all a. examples of situations that are “normal”—the body is trying to help cases), an you heal—but painful: inflammation to an 1) first line of defense (skin) is breached (ie. a cut or laceration from a area is indicated by knife→ area becomes red and sore as normal inflammation takes adding “itis” to an place → immediately, certain processes take place during organ or area: ex: appendicitis— inflammation which result in clot formation to stop bleeding→ inflammation of the fibrin components are weaved together to form a scab to appendix; seal the breach → eventually it becomes less painful as it heals. pancreatitis; otitis 2) a cut becomes infected→ inflammation increases and becomes (ear); laryngitis more painful but eventually it heals. (larynx), etc 3) you get an upper respiratory infection—the fever and aches are miserable, but you finally get well. 4. a normal inflammatory process is usually acute and short-lived 1) only considered a disorder when it “gets out of control,” occurs inappropriately, and/or becomes chronic (lasts longer than 2 weeks). 2) example of chronic inflammation: bacteria with cell walls that are resistant to breakdown by the phagocytes, or irritants (chemicals, a retained splinter or dust particles) that cause a prolonged inflammatory response. 5. purposes of inflammatory response--to facilitate shifting of substances from blood into injured / irritated tissue to: a. “clean up” the area, begin the clotting process, and ultimately promote healing. b. stimulate and enhance immunocyte response (i.e, the 3rd line of defense) as needed Inflammatory mediators are a subset of biochemical 6. components of the inflammatory response: mediators-- substances that act on the body in a variety of ways.  a. step 1: irritation /injury of tissue triggers same response anywhere in your body → stimulates “LEAKINESS” in three ways: 1) irritated /injured cells that make up the tissue undergo disruption to metabolic pathway, which leads to loss of 1 cell membrane integrity & leakage of fluid & other substances from all injured cells in the area (see page 3 of alt. tiss. lecture for mini concept map on this) 2) also, mast cell degranulation occurs: a) here & there throughout any tissue area in the body 2 are a specialized type of cell called MAST CELLS b) when they are stimulated by an irritant or injury, they will degranulate—that is, “leak” chemical “granules” c) these are local inflammatory mediators called, histamine, leukotrienes and prostaglandins (HLP) 3 3) HLP causes capillaries in the area to swell up but at the same time sort of “relax” (this is called vasodilation). The capillary becomes more permeable, then “leaks” plasma from the blood vessel into the tissue. a) the “leaked” plasma contains neutrophils, clotting factors & fibrin. b) if more inflammation is needed, the SYSTEMIC inflammatory mediators come to the area via the bloodstream to pour “FUEL ON THE FIRE;” these are called acute phase reactants -- examples are CRP (C-reactive protein) , complement, circulating prostaglandins (& many others). Two important points: Examples of acute phase 1) LINKING PROCESS WITH S&S: the capillary swelling and reactants (APR): cellular leakage that is part of most inflammatory response is partly what C-reactive protein (CRP), causes the S&S of swelling, heat, erythema & pain (the swelling causes circulating irritation to nerve endings in the area→ pain). prostaglandins, kinins, cytokines, complement & 2) No matter where the inflammation is occurring, the elements of all more clotting elements these steps in the process will be there in one way another. like factors. NOTE: ALWAYS think b. step 2: the neutrophils (phagocytic WBCs from the blood) and vasodilation & macrophages (phagocytic cells in the tissue) phagocytize (“eat” & “leakiness” of capillaries & other blood vessels destroy) any dirt, debris, dying tissue, and/or microbes they might when you think of find in the tissue area. inflammation, because no matter where and under Review of select leukocyte (WBC) types : (See prep & book for more info) what circumstances Mast cells—WBCs that are found in tissue instead of blood. inflammation is Macrophages--start life as circulating monocytes , & end up in the tissue as their home; they occurring, there is going are another type of “permanent” WBC of the tissue ; phagocytize microbes & other duties to be a degree of Neutrophils circulating phagocytes -- kill microorganisms in blood and tissue. vasodilation & increased Lymphocytes: T-lymphocytes & B-lymphocytes; AKA the immunocytes. capillary permeability in the area. This is very important in 1) the combination of plasma, phagocytes, dead tissue cells, understanding the effects of inflammation in bacteria, fibrin, etc, results in a thick fluid called exudate various disease processes as we study them throughout the course. 2) when there is little microbe involvement this exudate is a clear gold color (the color of the plasma that is leaking out in the area) and is called serous exudate; if there is also some blood, it is called serosanguinous.  3) if there is more microbe & WBC involvement—ie, infection— the exudate becomes especially thick & whitish or yellowish; this is known as purulent exudate or pus. d. step 3: if bacteria, viruses, or other microbes are a part of the “mix” above, macrophages will have phagocytized & processed them and now need help from the 3rd line of defense— the lymphocytes—which will help to kill the microbes, but will also create memory (immunity) of the microbe; to involve the lymphocytes, the macrophages will: Chemotactic substances: biochemical 1) secrete chemotactic substances to “call” immunocytes (usually mediators that summon OTHER T cell/CD4 lymphocytes) to come to the area via the substances to a certain area, or to increase in amount. bloodstream 2) display remnants of the microbes on their cell membranes as a guide to the T-lymphocytes: “this is our enemy… now create some more defenses.” e. step 4: clotting factors, platelets, and fibrin come together in various ways in the area to create healing, granulating tissue. Terms easy to confuse: Degranulation—breaking apart of mast cells with spillage of granules of biochemical mediators into tissue. Granulating tissue—pink, healthy, healing tissue. Granuloma—a hunk of tissue that has been chronically inflamed & is now essentially just scar tissue. 7. inflammatory response can be local (either local externally or local internally) or systemic (see #8) a. local external example—laceration or abrasion to skin. b. local internal examples: 1) appendix gets irritated by a piece of food or microbe→ normal inflammation responds to the irritation→ appendicitis (appendicitis becomes a disease process, because it is ultimately harmful to the body, but the initial inflammation was a normal defense of the body.) 2) pleuritis—inflammation of pleura when irritated by, for example, a lung cancer cell. 3) thyroiditis—thyroid is inflamed because of autoimmune attack. This is what we know so far about normal inflammation: When a tissue gets irritated or injured, local cells leak, and also mast cells of the tissue degranulate– ie, break down & release granules of certain biochemical mediators (such as leukotrienes, prostaglandins, and histamine) that cause capillaries in the area to vasodilate and then “leak.” This allows phagocytes (mostly neutrophils) & coagulatory substances to “leak out” of the blood and reach the injured area of tissue to help begin the healing process. There is also usually a thick fluid called exudate—a “soup” of phagocytes, dead tissue cells, bacteria, fibrin, etc.—which can be serous, serosanguinous, or purulent (“pus”), depending on its composition. If more inflammation is needed, circulating inflammatory mediators called acute phase reactants come to the area and increase all the above processes. In the area of injury, whether externally or internally, the combination of these processes causes the typical redness, swelling, heat, and pain of inflammation. If all goes well, healthy pink granulation tissue evolves at the irritation/injury site & healing is near complete. 8. NORMAL systemic inflammatory response a. overview 1) the steps in a systemic response are basically the same as a local one, but without a specific focus; systemic inflammatory response happens when the body needs the extra help of the  systemic “cavalry” like more leukocytes (leukocytosis) and more acute phase reactants (often causing fever) 2) any stressor (trauma, infection, etc.) which activates and involves a local inflammatory response can then cause the activation of a systemic inflammatory response. b. examples of normal systemic inflammatory response 1) a localized injury with infection of the big toe → local inflammation is initiated →local inflammatory mediators activate a systemic inflammatory response. 2) a localized infection of the bladder → local inflammation begins → the microbe or the microbes toxins enter the blood stream (bacteremia) → activates a systemic inflammatory response (cast of characters in the inflammatory mix: histamine, prostaglandin, leukotrienes, PLUS acute phase reactants such as CRP, large numbers of WBC’s). 3) a traumatic injury occurs (car accident) → local inflammation is initiated → local inflammatory mediators activate a systemic inflammatory response. c S&S of systemic inflammation may include; 1) malaise, aches & pains 2) fever (from response to increased prostaglandins & acute phase reactants) a) purpose of fever: has beneficial effect of directly killing some microorganisms b) but also can have deleterious effects heat dilates (1) fever can dilate blood vessels→ too much vessels; cold vasodilation = low blood pressure constricts vessels (2) also, fever increases metabolic rate→ may cause decompensation in very ill, debilitated, and/ or elderly patients. 3) lab tests As inflammatory mediators a) CBC will show increased WBCs – leukocytosis increase, they will exert more (1) leukocytes (WBCs) increase in number as they are chemotactic influence on WBCs—ie, “COME ON! JOIN “summoned” to the areas of inflammation. THE PARTY—WE MIGHT NEED (2) the WBC subtype that is usually most increased is YOUR HELP TO ATTACK neutrophils→ neutrophilia; ex of lab report MICROBES!” Neutrophils, showing leukocytosis and neutrophilia: especially will increase in (1) total WBCs count = 15,000 K/ul number, since they are key phagocytes. (norm~5-10,000) (2) percentage of neutrophils = 88% (norm~50-75%) b) serum CRP will often be elevated because it is an acute phase reactant – “fuel on the fire.”  FYI: Another blood test showing inflammation is an ESR (AKA sedrate). How ESR (erythrocyte sedimentation rate) works in showing that there is an inflammatory process: 1. An ESR tests how quickly RBCs will drop down to become “sediment” at the bottom of a test tube of blood. The usual, normal rate (speed) is ~ 15mm/hr. 2. The RBCs will tend to clump together if there are inflammatory entities such as fibrin in the plasma around the RBCs. As they clump, they will be heavier than usual and drop to the bottom faster. An example of an elevated ESR is 100mm/hr—a very high rate seen in acute inflammatory processes such as osteomyelitis **************************************************************************** (inflammation / infection of bone). SEE CONCEPT MAP: ALTERATIONS IN MECHANISMS OF DEFENSE IV. Abnormalities of Inflammation (ie, abnormalities in the 2nd line of defense) A. “Not enough” inflammation 1. defect in phagocytic functions Anyone with not enough a. quantitative defect (example—from chemotherapy) inflammation will be extra 1) leukopenia --deficiency in WBCs susceptible to infections. 2) specific deficiency in neutrophils-- neutropenia b. qualitative defects 1) chemotactic defects—won’t respond appropriately when “summoned.” 2) impaired function; ex—phagocytes damaged by diabetes mellitus have decreased ability to fight microbes. 2. complement deficiencies a. these are a group of disorders that stem from a genetic defect in synthesis of complement proteins b. patients who have defects in these have problems that are very similar to those seen in patients with antibody deficiencies— they will be extra susceptible to infections. C. Abnormalities of inflammation: “too much” inflammation 1. overview a. if all goes well, inflammation is usually acute and short-lived – it “gets the job done” as efficiently as possible and goes away, paving the way “Shock”—low BP for continued healing that causes b. abnormal inflammation is one in which inflammation goes into S&S; usually lower than 80 or “overdrive” and/or becomes chronic; examples include SIRS, sepsis 90 systolic. septic shock & chronic inflammation disorders. 2. SIRS – systemic inflammatory response syndrome a. occurs when a normal systemic inflammatory response goes into overdrive – the normal “braking” system of the inflammatory process does not occur. Instead, wide spread systemic inflammation occurs in the entire body, not just in the original injured or inflamed area. b. this excessive systemic inflammation contributes to widespread impaired tissue function and organ damage.  1) a localized injury with infection of the big toe → local inflammation is initiated →local inflammatory mediators activate a systemic response → instead of healing, systemic inflammation goes into overdrive → SIRS → widespread tissue/organ damage c. SIRS is present when 2 (usually more) of the following S & S are present; 1) unexplained change in mental status (confusion, not as awake ***Do memorize and remember, and alert as normal). “now and forever,” 2) fever of more than 100.4° F normal 3) increased heart rate temperature =98.6 ° F 4) increased respiratory rate 5) abnormal white blood cell count (WBC) 3. sepsis a. occurs when there is a known or suspected infection AND the person has SIRS. 1) a localized injury with infection of the big toe → local SIRS = “overdrive” of inflammation is initiated →local inflammatory mediators activate wide spread systemic a systemic response → inflammation overdrive → S&S of SIRS inflammation with related S&S → sepsis b. nurses are KEY to the early recognition of the S&S of SIRS and Sepsis = SIRS + infection the identification of sepsis so appropriate treatment can be started early. Suspect sepsis and “save lives”. Mortality (death of Septic shock = sepsis + low blood pressure a patient) increases by 10% every hour that treatment is delayed. Why? Because treatment, within the first hour of sepsis S&S, prevents…. http://www.survivingsepsis.org 4. septic shock a. occurs when sepsis (infection + SIRS) is complicated by low blood pressure. b. high levels of systemic inflammatory mediators trigger widespread, (normal arteries have a extreme vasodilation = no arterial vessel “tone” as arteries become certain “vasomotor too relaxed, “floppy”→ blood pools in periphery instead of being part tone”– the muscles in of circulation→eventually low blood volume reduces amount of O2 their walls constrict & being brought to tissues as well as decreasing BP dilate as body needs.) c. S&S of septic shock: 1) SIRS S&S – change in mental status, fever, increased heart rate, increased resp rate, abnormal white blood cells (WBCs) + 2) low BP. Low BP causes ischemia to organs so patient can have renal failure, respiratory failure, heart failure or death. 3. chronic inflammation a. difference between acute & chronic inflammation is duration—chronic lasts weeks or longer, regardless of cause b. inflammation can be prolonged to become chronic, due to persistent bacterial contamination, foreign objects (splinters, etc), autoimmune processes (discussed later)