Chapter 9 Stress and Adaptation General Adaptation Syndrome
(GAS) Hans Selye Stress as a term to mean an orchestrated set of
bodily responses to any form of noxious stimuli Selye injected rats
with ovarian extract and saw: Enlarged adrenal cortex Thymic
atrophy Bleeding ulcers in stomach and duodenum Stages of the
General Adaptation Syndrome (GAS) Alarm stage: arousal of body
defenses CNS aroused fight-or-flight concept Generalized
stimulation of the sympathetic nervous system and the HPA
(Hypothalamus-pituitary-adrenocortical axis) resulting in release
of catecholamines and cortisol Resistance or adaptation stage: Body
selects the most effective and economical channels of defense
Remove it or adapt to it If body does not adapt, it goes into the
exhaustion stage Adaptation implies that an individual has
successfully created a new balance between the stressor and the
ability to deal with stress Exhaustion stage: compensatory
mechanisms breakdown Resources are depleted and signs of wear and
tear appear, stress overwhelms the bodys defenses/disease or death
Increased cortisol levels = GI ulcers, etc. Homeostasis: the
purposeful maintenance of a stable internal environment Does not
occur by chance is the result of organized self-government
Physiologic processes opposing change each stress response
involves: Operates by negative feedback mechanisms constancy of the
internal environment When monitored function or value decreases
below the set point of the system, the feedback mechanism causes
the function or value to increase (ideally back to within set
point) When the function or value is increased above the set point,
the feedback mechanism causes it to decrease A sensor detects a
change An integrator/comparator sums and compares incoming data
with set point (normal) Effector system returns the sensed function
to within the range of the set point (normal) Functions of the
bodys control systems Regulate cellular function Control life
processes Integrate functions of the different organ systems Stress
A state manifested by symptoms that arise from the coordinated
activation of the neuroendocrine and immune systems (GAS)
Neuroendocrine responsesHormones associated with the stress
responseSource of the hormonePhysiologic effects
Catecholamines (NE, epinephrine)Locus Caeruleus (LC, adrenal
medullaIncrease in insulin release and increase in glucagon release
resulting in increased glycogenolysis, gluconeogenesis, lipolysis,
proteolysis, and decreased glucose uptake by peripheral
tissues.Increase in HR, cardiac contractility, and vascular smooth
muscle contractions.Relaxation of bronchial smooth muscle.
Corticotropin-releasing factor (CRF)HypothalamusStimulates ACTH
release from anterior pituitary and increased activity of the LC
neurons.
Adrenocorticotropic hormone (ACTH)Anterior pituitaryStimulates
the synthesis and release of cortisol.
Glucocorticoid hormones (e.g., cortisol)Adrenal
cortexPotentiates the actions of epinephrine and glucagon.Inhibits
the release and/or actions of the reproductive hormones and
thyroid-stimulating hormone.Produces a decrease in immune cells and
inflammatory mediators
Mineralocorticoid hormones (e.g., aldosterone)Adrenal
cortexIncreases sodium absorption by the kidneys.
Antidiuretic hormone (ADH vasopressin)Hypothalamus, posterior
pituitaryIncreases water absorption by the kidneys.Produces
vasoconstriction of the blood vessels.Stimulates the release of
ACTH.
Locus Caeruleus Central to the neural component of the
neuroendocrine response to stress Densely populated with neurons
that produce NE and is thought to be the central integrating site
for the ANS response to stressful stimuli LC-NE system has afferent
pathways to the hypothalamus, the limbic system, the hippocampus,
and the cerebral cortex Corticotropin-releasing factor (CRF) A
small peptide hormone found in both the hypothalamus and in
extrahypothalamic structures (limbic system and brain stem) Growth
hormones: decrease during stress Thyroid hormones: decrease during
stress Reproductive hormones: may decrease during stress ADH (from
posterior pituitary): increased = water retention and
vasoconstriction Cortisol (from adrenal cortex): suppresses immune
function, increases glucose levels = decreased healing, suppressed
inflammatory process, reduces WBCs to fight infections, stimulates
gastric acid secretion NE and epinephrine Everyday wear and tear on
the body Adaptation The ability to respond to challenges of
physical or psychological homeostasis and to return to a balanced
state Stressors Events or environmental agents responsible for
initiating the stress response Can be endogenous (age, gender,
genes) or exogenous (diet, environment) or a mix of both NOT ALL
STRESS IS DETRIMENTAL Types of stress Eustress: mild, brief,
controllable stress Distress: severe, long uncontrolled stress
Allostasis Physiologic changes in the neuroendocrine, autonomic and
immune system in response to altered homeostasis Factors affecting
ability to adapt Physiological reserve and previous learning Time:
acute or chronic Genetics Age: very old and very young less
adaptable Health status: other illnesses present may interfere with
adaptation Nutrition: deficiency or excess Sleep-wake cycles:
immunity affected Hardiness Psychosocial factors Physiologic
reserve The ability of the body systems to increase their function
given the need to adapt RBCs and oxygen your body can carry more
than you actually use Anatomic reserve Paired organs that are nor
needed to ensure the continued existence and maintenance of the
internal environment Lungs, kindeys, and adrenals you have 2 of
each so you can survive!! PTSD Intrusion (flashbacks) The
occurrence of flashbacks during waking hours or nightmares in which
the event is relived, often in vivid and frightening detail
Avoidance (emotional numbing) The emotional numbing that
accompanies this disorder and disrupts important personal
relationships-depression- may have survivor guilt Hyperarousal
(irritability, vigilance, exaggerated startles reflex, over concern
with safety) The presence of increased irritability, difficulty
concentrating, an exaggerated startle reflex, and increased
vigilance and concern over safety Must have these symptoms for at
least a month for a diagnosis of PTSD Nonpharmacologic tx for
stress Relaxation techniques Guided imagery Music therapy Massage
Biofeedback Cellular Adaptation, Injury, and Death All disease
processes and most injuries are a result of cellular injury or
death Cellular adaptation A cell responds to it environment by
adjusting structure and function to meet demands In response to
physiologic stresses or pathologic stimuli, cells adapt to achieve
a steady state (homeostasis) The adaptive responses are: Atrophy
(decrease in size) Cell shrinks in an attempt to reduce its
workload Hypertrophy (increase in size) 2 types Physiologic A
uterus enlarges in response to estrogen signals Pathologic The
enlargement of the heart in response to hypertension Hyperplasia
(increase in number) Cells that are capable of mitotic division
will accelerate mitosis in order to increase their number and
functional ability Metaplasia (change in form) When exposed to
persistent injury, cells will replace themselves with a different
type that is better able to deal with that injury Example: Barretts
Esophagus after long exposure to reflux Dysplasia A dysfunctional
effort to adapt Usually considered pre-neoplastic Cellular injury
In early stages, mild forms of cell injury us reversible in the
injurious agent is removed Continual cell damage and injury causes
an irreversible state that the cell cannot recover from and the
cell dies Causes of cell injury Oxygen deprivation Hypoxia most
common cause of cell injury Cell swells Anaerobic glycolysis tries
to compensate Lactate is produced Cellular pH, impairing other cell
functions This process can be reversed until plasma membrane and
mitochondrial membranes are critically damaged Interferes with
cellular metabolism and generation of ATP NO O2 = NO ATP! Decrease
in ATP slows cell processes The energy dependent Na+K+ pump Na+
accumulates in the cell drawing water in Highly reactive oxygen
species (ROS) Highly volatile free radicals will react with any
chemical with which they come in contact with Can damage proteins,
fats, DNA Chemical agents Some toxic chemicals are inherently
reactive Heavy metals (lead, mercury) Toxic gases (carbon monoxide)
Corrosives (acids, alkalis) Antimetabolites (cyclophosphamide,
vincristine) Physical agents Mechanical forces Direct trauma to
cell membranes Blunt force trauma Direct penetrating trauma
Hypothermic injury Severe vasoconstriction and increased blood
viscosity causes ischemia With continued exposure, vasodilation may
occur Cytosol freezes and intracellular ice crystals form
Hyperthermic injury Microvascular coagulation Increased metabolic
processes Direct tissue destruction Electrical injury Cells of the
body act as conductors of electricity Neural and cardiac impulses
are interrupted Hyperthermic destruction occurs Current flows
through the path of least resistance Electromagnetic radiation
Direct-hit: breakage of chemical bonds holding DNA together
Ionizing radiation: orbital electrons are knocked off Activated
oxygen molecules act like free radicals and steal other electrons
Genetic damage Radiation induced cell death Infectious agents
Immunological reactions Genetic defects Nutritional imbalances Most
vitamins, minerals, and some amino acids must come from diet Cell
injury can come from a deficiency or excess of nutrients Aging
Reversible cell injury and cell death Cell destruction and removal
can involve 2 mechanisms Apoptosis Programmed cell death Highly
selective process that eliminates injured and aged cells thereby
controlling tissue regeneration Cell death/necrosis Refers to cell
death in an organ or in tissues that are still part of a living
person Cellular autodigestion Also initiates an inflammatory
process In contrast to apoptosis which functions in removing cells
so new ones can replace them, necrosis often interferes with cell
replacement and tissue regeneration Gangrene occurs with a
considerable mass of tissue undergoes necrosis Types of necrosis
Liquefaction neuron and glial cells of the brain Turn to softened
center of abscess with discharge of contents Cells dies but
catalytic enzymes are not destroyed Coagulation Dead cells convert
to gray, firm mass Opaque state Seen in heart, kidney, and adrenal
glands Caseous exclusive to TB Body walls this off and middle
becomes white, soft, and fragile Dead cells persist as a
cheese-like debris in lungs Immune mechanism Gangrene (wet/dry/gas)
When a considerable amount of tissue undergoes necrosis Dry SLOW
Affected tissues becomes dry and shrinks, skin wrinkles Color
changes to dark brown or black Causes an inflammatory reaction Line
of demarcation between dead and healthy tissue Typically and
arterial problem Mainly confined to the extremities (clot) Wet
RAPID It is a form of liquefaction necrosis Due to interference of
venous blood return Affect area is cold, swollen, and pulseless
Skin is moist, black, and under tension Blebs form on the surface
Liquefaction occurs Foul odor caused by bacterial action Can become
systemic = death if not stopped Can affect internal
organs/extremities Dry can convert to wet if bacteria invade Gas
RAPIDLY FATAL Gangrene that results from clostridium bacteria,
usually clostridium perfringes Anaerobic spore-forming organisms
Produce toxins that cause cell membrane to dissolve = edema, death
to muscle cells, renal failure Prone to occur in trauma and
compound fractures in which dirt and debris are embedded in wounds
Produces hydrogen sulfide gas This is why it is so serious and
rapidly fatal Antibiotics are used and may need surgical
intervention and amputation to stop the spread Phases of wound
healing Inflammatory Begins at time of injury Prepares wound
environment for healing Hemostasis first (to promote blood
clotting) Next come the vascular and cellular phases of
inflammation Cleans debris (phagocytosis) WBCs Promotes growth of
blood vessels Attracts fibroblasts Proliferative Begins 2-3 days
after injury, may last 3 weeks Fibroblasts synthesize collagen
(peaks in 5-7 days) Proliferation of fibroblasts and vascular
endothelial cell form granulation tissue serve as foundation of
scar tissue Tissue is fragile, bleeds easily due to newly
developing capillary beds Remodeling (Maturation) Begins 3 weeks
after injury; lasts for months to 2 years Continuous remodeling:
collagen synthesis and lysis of scar tissue cell Increases tensile
strength of the wound over time Really only ever gets to 70-80% of
normal strength
Neoplasia Characteristics of cancer Disorder of altered cell
differentiation and growth results in neoplasia (new growth) Growth
is uncoordinated and relatively autonomous Lacks normal regulatory
controls over cell growth and division Tends to increase in size
and grow after stimulus eases or needs of the organism are met
Components of tissue renewal and repair Cell proliferation Process
of cell division Inherent adaptive mechanism for replacing body
cells Cell differentiation Process of specialization New cells
acquire the structure and function of cells they replace Apoptosis
A form of programmed cell death to eliminate unwanted cells Cell
division G1 (gap 1): the postmitotic phase DNA synthesis ceases,
while ribonucleic acid (RNA) and protein synthesis and cell growth
take place S phase: DNA synthesis occurs Gives rise to 2 separate
set of chromosomes, one for each daughter cell G2 (gap 2): the
premitotic phase DNA synthesis ceases RNA and protein synthesis
continues M phase: the phase of cellular division or mitosis Stem
cells Reserve cells that remain inactive until there is a need for
cel replacement Self-renewal Potency Totipotent: produced by
fertilization of an egg Can differentiate into embryonic and
extraembryonic cells Pluripotent: can differentiate into the three
germ layers of the embryo (echoderm, mesoderm, endoderm: all
organs) Multipotent: give rise to only a few cell types Unipotent:
give rise to one type of differentiated cell, but retain the
property of self-renewal Muscle satellite cell Epidermal stem cell
Spermatogonium Basal cell of the olfactory epithelium Tumors Adding
the suffix oma to the parenchymal tissue type from which the growth
originated Neoplasms Benign Slow, progressive rate of growth that
may come to a standstill or regress An expansive manner of growth
Inability to metastasize to distant sites Composed of
well-differentiated cells that resemble the cells of the tissue of
origin Malignant Grow rapidly and spread widely Have the potential
to kill regardless of their original location Compress blood
vessels and outgrow their blood supply, causing ischemia and tissue
necrosis Rob normal tissues of essential nutrients Liberate enzymes
and toxins that destroy tumor tissue AND normal tissue Factors that
differentiate benign and malignant tumors Cell characteristics
Benign = well-differentiated cells Malignant = loss of
differentiation in cells Manner of growth Benign = expansive manner
of growth, but typically remain in one place Malignant = use
seeding, direct invasion, and blood/lymph to grow Rate of growth
Benign = slow and progressive Malignant = rapid and spread widely
Potential for metastasizing or spreading Benign = little chance of
metastasizing Malignant = great chance of metastasizing Tendency to
cause tissue damage Benign = tissue damage minimal Malignant =
compresses blood vessels causing ischemia and tissue necrosis
Liberates enzymes that may kill both tumor tissue but healthy
tissue as well Capacity to cause death Benign = may press on vital
organs, but overall lower potential of death Malignant = may
rapidly invade or seed into organs and other sites which give high
chance of death Anaplasia = term used to describe the loss of
differentiation in cancerous tissue cells Genes that control cell
growth and replication Proto-oncogenes normal genes that become
cancer causing oncogenes if mutated They are heavily involved in
growth factors and promoted cancer when turned on They get
erroneously activated Tumor suppressor genes They actually inhibit
cellular proliferation, but when switched off they can create an
environment in which cancer is promotes TP53 gene mutation in this
gene is implicated in the development of breast, lung, and colon
cancer Genes that control programmed cell death or apoptosis Genes
that regulate repair of damaged DNA Steps involving the
transformation of normal cells into cancer cells Initiation
irreversible event Cell exposed to doses of carcinogenic agents
making them susceptible to malignant transformation Proliferation
is required (cell must be able to divide) Promotion Unregulated
accelerated growth in already initiated cells caused by various
chemical and growth factors Progression Tumor cells acquire
malignant phenotypic changes that promote invasiveness, metastatic
competence, autonomous growth tendencies, and increased karyotypic
instability DNA damage (mutation) Initiation Proliferation (growth
promoters) promotion Development of cancerous phenotype progression
Detectable tumor size is 1 cm by then it already has 1 billion
cells in it Tumors cannot grow more than about 2mm unless they grow
blood vessels into the tumor (angiogenesis) Treatments Chemotherapy
Radiation Contraindicated in childhood cancer treatment as it has
been shown to have long-lasting and even delayed effectsInnate and
Adaptive Immunity Immune response Immune response = the collective,
coordinated response of the cells and molecules of the immune
system to protect against infectious disease Purpose of the immune
system To neutralize, eliminate, or destroy microorganisms that
invade the body To recognize and eliminate aberrant cell like
cancer Immune Defenses Innate/NON-specific immunity The natural
resistance a person is born with Adaptive/Specific immunity 2nd
line of defense Response is less rapid than innate, but more
effective Can also produce undesirable effects: Allergies: an
excessive immune response Autoimmune disease: immune system
recognizes self-tissue as foreign Components of the immune system
Skin, mucous membranes, phagocyte system, lymphoid system (spleen,
thymus gland, and lymph nodes), bone marrow Principle cells in the
immune system Lymphocytes: recognize and respond to foreign
antigens Accessory cells: Macrophages and dendritic cells
(monocytes) Function as antigen-presenting cells by the processing
of a complex antigen into epitopes required for the activation of
lymphocytes Mediators of immune system Cytokines Soluble proteins
secreted by cells of both the innate and adaptive immunity
Chemokines Cytokines that stimulate the migration and activation of
immune and inflammatory cells Colony-stimulating factors Stimulate
the growth and differentiation of bone marrow progenitors of immune
cells Cells in innate immunity Macrophages Dendritic cells bridge
between innate and adaptive immunity Mast cells NK cells Can be
divided into 2 main subsets based on their ability to excrete
proinflammatory cytokines Ability to spontaneously kill target
organisms which relies on the recognition of specific PAMPs with
the microorganism type Complement proteins Basophils Eosinophils
Neutrophils Granulocytes Cells in adaptive immunity B cells
antibodies T cells CD4+ T cells CD8+ T cells Components for Innate
immunity Epithelial barriers Phagocytic cells (neutrophils and
macrophages) NK cells Plasma proteins Opsonins facilitates
phagocytosis Cytokines chemical signaling TNF (tumor necrosis
factor) Interleukins (IL) Interferons (IFN) Chemokines Acute-phase
proteins/reactants Two types Mannose-binding ligand binds
specifically to mannose residues C-reactive protein binds to both
phospholipids and sugars that are found on the surface of the
microbes Both act as costimulatory opsonins and enhance the binding
of phagocytic cells to invading microorganisms Complement system a
process that involves plasma proteins found in the blood which are
essential for the activity of antibodies When foreign bodies
invade, this system activates Primary function: promotion of
inflammation and destruction of the microbes Three phases of
complement system reactions Initiation or activation Activation by
one of the three pathways listed below Amplification of
inflammation All pathways lead to the activation of complement
protein C3 and its enzymatic cleavage into C3b (larger) and C3a
(smaller) segments C3a = chemoattractant for neutrophils C3b =
becomes attached to the microbe and acts as an opsonin for
phagocytosis and acts as an enzyme to cleave C5 into 2 components
C5a = produces vasodilation and increases vascular permeability C5b
leads to late-step membrane attack responses Membrane attack
response C3b bind to other complement proteins to form an enzyme
that cleaves C5 C5a = stimulates the influx on neutrophils in the
vascular phase of acute inflammation C5b = remains attached to the
microbe initiates the formation of a complex of complement proteins
C6, C7, C8, and C9 into a membrane attack complex protein, or pore
that allows fluids and ions to enter and cause cell lysis Multiple
pathways that result in recognizing microbes and complement system
activation Classic pathway Activated by certain types of antibodies
bound to antigen and is part of humoral immunity Lectin pathway
Activated by plasma lectin that binds to mannose on microbes and
activates the classical pathway in the absence of antibody
Alternative pathway Activated on microbial cell surfaces in the
absence of antibody Is a component of innate immunity Cytolysis
Opsonization Chemotaxis Anaphylaxis Adaptive immunity Types of
adaptive immune response Humoral immunity/antibody mediated
Mediated by molecules in the blood The principal defense against
extracellular microbes and toxins Cellular immunity/cell mediated
Mediated by specific T lymphocytes Defends against intracellular
microbes such as viruses Lymphocytes B cells Humoral immunity that
have memory Produce antibodies Matures in the bone marrow and
differentiate into memory cells or immunoglobulins IgA found in
mucous, saliva, tears, and breast milk. Protects against pathogens
IgD part of the B cell receptor. Activates basophils and masts
cells IgE protects against parasitic worms. Responsible for
allergic reactions IgG Secreted by plasma cells in the blood. Able
to cross the placenta into the fetus IgM may be attached to the
surface of a B cell or secreted into the blood. Responsible for
early stages of immunity Antigens are substances foreign to the
host that can stimulate an immune response Production begins about
72 hours after exposure Antibodies recognize antigens Receptors on
immune cells Secreted proteins
T cells Cell mediated immunity that have memory Destroys
antigens Matures in the thymus Regulatory cells (helper and
suppressor cells) Assist in orchestrating and controlling the
immune response Helper T cells activate other lymphocytes and
phagocytes Regulatory T cells keep these cells in check so that an
exaggerated immune response does not occur Cytotoxic T cells
effector cells Effector cells (killer cells) Accomplish the final
stages of the immune response with the elimination of the antigen
Activated T lymphocytes, mononuclear phagocytes, and other
leukocytes function as effector cells in different immune responses
An antigen presenting cell (APC) eats a virus the APC breaks down
that virus molecule but take a piece of it and presents it on the
cell surface via a major histocompatibility complex type 2 (MHC II)
A helper-T cell with a T cell receptor attaches to the epitope of
the virus piece (antigen) which activates the helper-T cell
helper-T cell sends out cytokines to cytotoxic T cells so that they
can bind to the viral epitope of the target cell via the T cell
receptor (TCR) and releases toxic materials into the target cell
resulting in target cell death the helper-T cell sends out
cytokines which activates the B cell with membrane bound Ig
molecules that make up receptor sites that can bind with specific
epitopes of antigens that the B cells then divide several times to
form populations (clones) of cells that continue to differentiate
into several types of effector and memory cells (helper-T cell
differentiates into the cytotoxic [as stated before] and memory T
cells; B cells differentiate into plasma cells [to make more
antibodies for that specific antigen] and memory B cell) B cells
may even recognize and antibody before the T cell and interact with
a helper-T cell by presenting part of the antigen on its surface
via an MHC II and connecting with the TCR on the helper-T cell MHC
helps immune system recognize foreign substances Class I: all
nucleated cells Present processed antigen to cytotoxic CD8+ T cells
Restrict cytolysis to virus-infected cells, tumor cells, and
transplanted cells Class II: are immune cells, APC, B cells, and
macrophages Present processed antigenic fragments to CD4+ T cells
Necessary for effective interaction among immune cellsInflammation,
Tissue Repair, and Wound Healing Immunity First line of defense:
innate immunity Second line of defense: Inflammation Third line of
defense: Adaptive immunity Inflammation Goals: Limit and control
the inflammatory process Prevent and limit infection and further
damage Initiate adaptive immune response Initiate healing
Inflammatory response is a protective mechanism that is stimulated
when tissue is injured 3 purposes: Neutralize invading agents Limit
spread to other tissues Prepare damages tissue for repair
Inflammatory response involves: Vascular response Vasoconstriction
from seconds to 10 minutes Produces tissue hypoxia and acidosis
Vasodilation follows vasoconstriction Produces redness, pain, heat,
edema, and impaired function Platelets move to site and adhere to
vascular collagen Platelets release fibronectin (fibrin) to form
meshwork and stimulate clotting Venous capillaries become permeable
Fluid (protein-rich) leaks into the surrounding tissue to wall off
the site Also is the exudate As fluid moves out of the vessels,
stagnation of blood occurs allowing for next phase Cellular
response Margination and adhesion Leukocytes (mainly) neutrophils
(that were recruited to the site on injury via cytokines) line the
endothelium of blood vessels Transmigration Leukocytes (mainly)
neutrophils slide through pores of the vessels into the inflamed
tissue Chemotaxis Migration of leukocytes (mainly) neutrophils to
site of tissue injury via a chemical gradient (like chemokines)
Activation of leukocytes (mainly) neutrophils Enclose the foreign
substances Intracellular killing Chemical response Activated
granulocytes, lymphocytes, and macrophages release chemical
mediators Histamine (released by mast cells and basophils Among
first to be released during acute inflammation Increases
vasodilation and vascular permeability Primary activator of
endothelial cell retraction H1 receptor: smooth muscle cells in
bronchi H2: parietal cell of the stomach mucosa Bradykinins
(activated kinin system results in its release) Increases vascular
permeability Vasodilates Contracts smooth muscle cells Platelet
activating factor Generated from a complex lipid stored in cell
membrane Induces platelet aggregation Activates neutrophils Potent
eosinophil chemoattractant Cytokines IFN Primarily protect host
against viral infections Primarily play role in modulation of
inflammatory response IFN and IFN produces primarily by macrophages
IFN produced primarily by T lymphocytes TNF Endogenous pyrogen
Induces synthesis of proinflammatory substances in liver Prolonged
exposure can cause intravascular coagulation with subsequent
thrombosis production IL Produced by macrophages and lymphocytes
Produced in response to presence of invading microorganism or
activation of inflammatory process Primary function is to enhance
acquired immune response though: Molecular expression Induction of
leukocyte maturation Enhance leukocyte chemotaxis General
enhancement or suppression of inflammatory process Arachidonic acid
Released by phospholipases Initiates series of complex reactions
which Leads to production of eicosanoid family inflammatory
mediators Lipooxygenase (LOX) Leukotrienes Induces smooth muscle
contraction Constricts pulmonary airways Increases microvasculature
permeability Cyclooxygenase (COX) Prostaglandins Induces
vasodilation and bronchoconstriction Stimulate platelet aggregation
Act as chemotactic factor Responsible for increased sensation of
pain Thromboxane Vasoconstricts Increases bronchoconstriction
Promotes platelet function Aspirin and other NSAIDs work as COX
inhibitors Acute and chronic inflammation Acute Of relatively short
duration Nonspecific early response to injury Infiltration of
neutrophils Aimed primarily at removing the injurious agent and
limiting tissue damage Heat, swelling, redness, pain, exudative
fluids Exudate Serous watery exudate: indicates early inflammation
Fibrinous Thick, clotted exudate: indicated more advanced
inflammation Purulent pus: indicated a bacterial infection
Sanguineous/hemorrhagic contains blood: indicated bleeding Systemic
manifestations Fever Sepsis Leukocytosis Increased number of
circulating leukocytes Increased plasma protein synthesis Acute
phase reactants C-reactive protein Fibrinogen Haptoglobin Chronic
Self-perpetuating and may last from weeks to years Infiltration by
mononuclear cell (macrophages) and lymphocytes Proliferation of
fibroblasts Unsuccessful acute inflammatory response
Characteristics Dense infiltration of lymphocytes and macrophages
Granuloma formation Epithelioid cell formation Giant cell formation
Wound healing Primary intention Wounds that heal under conditions
of minimal tissue loss and wound edges are approximated Secondary
intention Great loss of tissue with contamination Phases of wound
healing Inflammatory Begins at time of injury Prepares wound
environment for healing Hemostasis first (to promote blood
clotting) Next come the vascular and cellular phases of
inflammation Cleans debris (phagocytosis) WBCs Promotes growth of
blood vessels Attracts fibroblasts Proliferative Begins 2-3 days
after injury, may last 3 weeks Fibroblasts synthesize collagen
(peaks in 5-7 days) Proliferation of fibroblasts and vascular
endothelial cell form granulation tissue serve as foundation of
scar tissue Tissue is fragile, bleeds easily due to newly
developing capillary beds Granulation, epithelialization, collagen
formation Remodeling (Maturation) Begins 3 weeks after injury;
lasts for months to 2 years Continuous remodeling: collagen
synthesis and lysis of scar tissue cell Continuation of cellular
differentiation Scar tissue formation Scar remodeling Increases
tensile strength of the wound over time Really only ever gets to
70-80% of normal strengthDisorders of the Immune Response
Alterations of the immune system Hypersensitivity or allergic
reactions Inappropriate or excessive activation of the immune
system 4 types Type I IgE mediated (immediate hypersensitivity)
Begins rapidly following antigen challenge Allergic reaction
Anaphylaxis Begins with mast cell of basophil sensitization Mast
cells are normally in connective tissue beneath skin and mucous
membranes of respiratory, GI, and Gu tracts Primary or initial
phase response 5-30 minutes after exposure Vasodilation Vascular
leakage Smooth muscle constriction Histamine mediated Secondary or
late phase response 2-8 hours after exposure and may last several
days Intense infiltration of tissues with inflammatory cells Tissue
destruction and epithelial damage Arachidonic acid and cytokine
mediated Type II antibody mediated Reaction is mediated by IgG or
IgM 3 mechanisms reactions can affect cell Cell destruction by
activation of complement cascade Antibody dependent cell mediated
cytotoxicity NK cells release toxins Antibodies cause cell
destruction through phagocytosis Hemolytic disease of newborns Rh
factor Mismatched blood transfusions Cell inflammation caused by
neutrophil by-products (reactive oxygen intermediates and enzymes)
Cell dysfunction which prevents normal interactions by
inappropriately stimulating or destroying the receptor Graves
disease Myesthenia Gravis Type III complex mediated Insoluble
Antigen-Antibody (immune) complexes formed in circulation and
deposited in vessel walls or tissues. Binds to soluble antigen
released into blood or body fluids and subsequently deposited in
tissues (large area) Once deposited, immune response elicits an
inflammatory response and lysosomal enzymes are released into the
inflammatory site instead of into the phagolysosomes causing tissue
damage Systemic Immune Complex Serum sickness (antibiotics, food,
venom), autoimmune vasculitis, glomerulonephritis Local Immune
Complex Arthus Reaction Type IV cell mediated Cell-mediated:
sensitized T cells attack antigen Direct cell-mediated cytotoxicity
Cytotoxic T cells Viral reactions Hepatisis Delayed-type
hypersensitivity Macrophages, T helper cells Tuberculin test,
allergic contact dermatitis, hypersensitivity pneumonitis
Transplant rejection Categories of transplant tissue: ALLOGENIC:
may or may not be related but have similar HLA types SYNGENEIC:
identical twins AUTOLOGOUS: same person Organ graft rejection
Hyper-acute Circulating antibodies react with the graft Type III
Arthus-type reaction Immediate post transplant Acute Generation of
T cells, antibodies against graft Within first few months post
transfer Chronic Blood vessels in the graft gradually damaged
Manifests in the dense intimal fibrous tissue of blood vessels in
the transplanted organ Mechanism is NOT well understood Prolonged
period of time GRAFT vs Host Disease (GVHD) Transplant needs a
functional immune component. Host tissues has antigens foreign to
donor tissue. Host immunity compromised. Autoimmune disorders
Normally, self-reactive immune cells are destroyed or suppressed.
In autoimmunity, self-tolerance breaks down and the immune system
attacks self-antigens destroys body tissues Autoimmune disorders
Systemic Lupus Erythematosus (SLE) Autoimmune Hemolytic Anemia
(AIHA) Hashimoto Thyroiditis Immunodeficiency states Primarygenetic
Humoral (B-cell) deficiencies Cellular (T-cell) deficiencies Severe
combined immunodeficiencies (SCID) Wiskott-Aldrich syndrome
Acquiredconsequence of another event Malnutrition Immunosuppressant
drugs AIDS