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PATHOLOGY EXAM #1
PHYSIOLOGY VS. PATHOLOGY
 What happens when normal physiology breaks down and disease manifests?
o Individual
 Goes to dr.
o Clinical
 testing
o diagnosis
 medical
 long lists to diagnose including labs, biopsies, stains, imaging, etc
 rehab
 uses physical (hands on) diagnosis
o treatment
 after diagnosis, how you deal
 rehab brings in activities and assesses why you cant do something and bring in solutions
Pathogenesis of Disease
 pathology
o cause
o mechanism of development
o methods
 pathogenesis
o development of disease
 clinical pathology
o applied solution to clinical problem
Definitions
 Etiology
o Study of pathogens that cause disease
 Diagnosis
o Recognition of a disease by its outward signs
 Prognosis
o How will the disease progress
 Average life expectancy
o Time period in which 50% of a certain population group (women) have died
 Incidence
o # of new occurrences of a certain disease (per year and 100,000 population)
 Prevalence
o # of persons per 100,000 who suffer from a certain disease on a certain day
 Signs
o Objective evidence of disease (see it)
 Symptoms
o Subjective evidence of disease (complaints)
 Syndromes
o Group of signs and symptoms that occur together
 Acute
o Intense and last a few days or weeks
 Subacute
o Characterized by an insidious onset and clinical course that lasts weeks
 Chronic
o Permanent
o residual
o rehabilitation
 Psychological
o Can depend on culture
Pathophysiology for health practitioners
 How does this particular disease or condition affect the person’s functional abilities and functional outcome?
 What precautions, monitoring should be taken when someone with this condition is exercising?
 How will understanding of the disease process affect the goals and treatment plan?
Cell Injury
 Most diseases begin with cell injury
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Injury may be mild and lead to sublethal changes or moderate to severe and lead to lethal changes
After cell injury
o Inflammation response meets the level of demand
 Healing allows restoration of structure and function when possible
 Ideal situation is regeneration of tissue but this is not often possible and non functional connective tissue develops
(fibrosis, scar tissue)
Stressors to Cells
 Ischemia
 Infectious agents
 Immune reactions
 Genetic factors
 Nutritional factors
 Physical factors
 Chemical factors
o Each of these lead to:
 Reversible (sublethal) OR irreversible (lethal) cell injury
Reversing cell injury will depend on?
 Intensity
 Duration
 Type, severity, and duration of injury
 Adaptive processes of cell
 Type of cell
 Level of differentiation
o Example
 One cell differentiates into 2 cells which each differentiate into other cells
 Like a red blood cell
 If you damage an undifferentiated cell then it will damage all of the cells that differentiate
from them
 Modifying factors: nutritional state
Ischemia
 Due to reduction in flow or increase in metabolism
o Hypoxia (partial)
 Hypoxemic ischemia (local anemia)= decrease amount of O2
 Ischemic hypoxia (stenosis)= decrease flow
o Anoxia (total)
 Examples
o Obstruction of pulmonary tree
o Inadequate transport of O2 across lung surface
o Inadequate transport of O2 to blood
o Inability of cell to use O2 (chemical poisoning)
 Can result in cell death (necrosis)
Infectious Injury
 Microorganisms
 Bacteria and viruses are responsible for the vast majority of infections
 Mechanism depends on ability to
o Invade and destroy cells
o Produce toxins that cause cell lysis
o Produce damaging hypersensitivity reactions
 Bacteria
o Primarily by invasion of tissue, releasing endotoxins that cause cell to lyse degrading the extracellular
matrix (spread)
o Injury can also result form the inflammatory/immunologic response included
 Clostridium tetani (tetanus)- selective to alpha motor neurons blocks inhibitory neurotransmitter
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When microorganism or their toxins are present in the blood = sepsis--- traveling thru whole body
o Endothelial damage, loss of plasma volume, hypovolemia
o Cardiovascular collapse may ensue and lead to “septic shock”
Viruses kill cells by 2 mechanisms
o Direct cytopathic effect (RNA viruses)
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 Disturb the cellular processes or integrity of the nucleus and/or plasma membrane
 Virally encoded proteins become inserted in membrane altering permeability
o Indirect cytopathic effect (DNA viruses)
 Integrate themselves into cellular genome producing foreign proteins
 If immune system is compromised or number of invading microorganisms overwhelms, symptoms
of illness occur
Immune Reactions
 Mechanisms by which the immune system can lead to cell injury or death
o Antibody attachment
o Complement activation
o Activation of inflammatory cells
 Normally the immune system functions in defense against foreign antigens but can become overzealous in its
activity leading to hypersensitivity reactions
Immune Reactions
 Allergies- high level of antibody (IgE)
o Mild, moderate, severe
o Excess deposition of antigen/antibody in glomeruli can lead to kidney damage
 Cross reactivity between foreign and host antigens may lead to cellular injury
o Rheumatic fever (Group A streptococcal pharyngeal infection)
 Chronic persistence of an organism may lead to
o Chronic inflammatory reaction (granuloma)
Genetic Factors
 Lead to cell injury or death by 3 primary means
o Alteration in structure & # of chromosomes inducing multiple abnormalities
o Single mutations of genes causing changes in the amount or function of proteins
o Multiple gene mutations that interact with environmental factors
o Examples
 Downs syndrome
 Sickle cell anemia
 Type 2 diabetes
Nutritional Imbalances
 May present cellular effects when wither deficiencies or excesses occur
 Examples
o Protein, glucose deficiency
o Hypo or hyperlipidemias
o Protein-calorie malnutrition
o Vitamin deficiencies
 Particularly may create pathology if occur during growth and development
Physical Factors
 Trauma and physical agents may injury cells
 Blunt force injuries
o Result in tearing, shearing and crushing tissues
o May be caused by blows, impact
o MVAs and falls are the most common causes
 Examples
o Contusion (bruise)
o Hematoma
o Abrasion (a scrape)
o Laceration (tear or rip)
o Fractures
 Sharp force injuries
o Cutting, piercing injuries
 Examples
o Incision
o Stab wound
o Puncture wound
o Chopping wound
 Temperature extremes
o Hypothermic injury
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 Frostbite results form chilling or freezing of cells
Hyperthermic Injury
 Burn is caused by excessive heat and varies in severity according to the nature, intensity, and
extent of heat
 Ionizing Radiation
o Radiation that can remove orbital electrons from atoms
 Illumination
o Fluorescent lighting and halogen lamps create harmful stresses. UV light has been linked to skin cancer
 Mechanical Stresses
o Injury is caused by physical impact or irritation; they may be overt or cumulative
 Noise
o Can be caused by acute loud nose or the cumulative effects of various intensities, frequencies, and
duration of noise
 Atmospheric pressure
o Compressive waves of ari or fluid impinging on the body
o Changes may collapse the thorax, rupture internal solid organs and cause widespread hemorrhage
o CO2 and Nitrogen that are normally dissolved in blood come out of solution
Chemical Injuries
 Interaction between a toxic substance and the cell’s membrane
 Membrane is damaged
 Leads to increased permeability
 Examples
o Small amounts of hightly toxic posisons (ex arsesic cyanide) can cuase death
o Chronic exposure to air pollution, insecticides, and herbaicides
o PB, CO, CCl4 and social drugs such and alcohol
o Recreational, OTC and prescribed drugs
Reversible Cell Injury
 A sublethal or reversible injury
o Stress is small in magnitude or short in duration that the cell is able to recover
Cellular adaptations to chronic cell injury
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Cellular Adaptation
 Allows cells to function in an altered environment
 Protects cells from injury
 Increases ability to survive
 Changes are potentially reversible
Atrophy
 Decrease or shrinkage in cellular size
 Most common in skeletal muscles
 Causes include decreased:
o Workload or use
o Blood supply
o Nutrition
o Hormonal and or nervous stimulation
Hypertrophy
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Definition
o An increase in the size of cells and consequently in the size of the affected organ
 Most common in cells of the heart and or the kidneys
 Tends to diminish if the workload diminishes
Hyperplasia
 Definition
o An increase in the number of cells resulting form increased rate of cellular division
o When injury has been severe & prolonged enough to cause loss of cells
 Cell loss triggers DNA synthesis and mitotic division
o Compensatory hyperplasia
 Enables organs to regenerate
o Hormonal hyperplasia
 Endometrial hyperplasia
o Pathological hyperplasia
 Tumor
Dysplasia (atypical hyperplasia)
 Refers to abnormal changes in the size, shape and organization of mature cells
 Considered a form of hyperplasia
 Considered a form of hyperplasia
 Frequently encountered int eh epithelial tissue of cervix and repiratory tracts
 Often associated with cancerous cells
Metaplasia
 Reversible replacement of one mature cell type by another, sometimes less differentiated cell type
 Example is replacement of columnar epithelium of the bronchial lining to squamous epithelium
 Can often be reversed if the stimulus is removed (smoking)
Intracellular Accumulations or Storage
 Intracellular accumulations
o Lipids, proteins, carb, or pigments
 Occurs when
o A normal, endogenous substance is produced in excess
o And endogenous substance is not effectively catabolized
o Harmful exogenous materials (such as heavy metals, mineral dusts or micororganisms) accumulate
 Inhalation, ingestion or infection
Irreversible cell injury = cell death
 Hallmarks=
o Alterations of nucleus, mitochondria, lysosomes
o Cell membrane rupture
 Cellular death eventually leads to cellular dissolution or necrosis
 Apoptosis
o Is an active process of cellular self-destruction
Nucleus Damage- (hallmark of Necrosis)
 Damage to the nucleus can present in 3 forms
o Pkynosis (clumping)
o Karyorrhexis (fragmenting fo pkynotic nuclei)
o Karyolysis (dissolution)
 The sum of cellular changes after local cell death & the process of cellular self-digestion known as auto-digestion,
or autolysis
Common themes in cell death & injury
 ATP depletion (mitochondria)
o Results: mitochondrial & cellular swelling, decrease protein synthesis, decrease membrane transport
 Decrease Oxygen
o Activation of free radicals (unpaired electron), destruction of membrane and cell structure
 Intercellular calcium
o Ischemia causes increases, activates damaging enzymes
 Defects in membrane permeability
o Loss of selective permeability damage cells
 After cell death, lysosomes release their digestive enzymes causing degradation= necrosis
Types of Necrosis
 Different types of necrosis occur in different organs or tissues
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o Sometimes can indicate the mechanism or cause of cellular injury
The major types
o Coagulative necrosis
 Ischemia
 Cell membrane preserved, nucleus undergoes pyknosisi and karyolysis
 Primarily in kidneys, heart, and adrenal glands
o Liquefactive necrosis
 Results from
 Pyogenic bacterial infection
 Ischemic injury to neurons and glial cells in the brain
 Cells are digested by their own hydrolases
 Tissue becomes soft, liquefies, and forms cysts
o Caseous necrosis (cheesy)
 Results from tuberculous infection & fungal infections
 Mycobacterium tuberculosis)
 The dead cells disintegrate incompletely and a wall encloses areas
 Tissues resemble clumped cheese, soft and granular
o Fatty necrosis
 Occurs in the breast, pancreas, and abdominal structures
 Caused by enzymes which brake down triglycerides
 Releasing free fatty acids
 The necrotic tissue appears opaque and chalk white
o Fibrous
 Trauma to blood vessels (plasma proteins accumulate)
 Gangerous necrosis
o Not a distinctive type of cell death but refers to larger areas of tissue death
o Results from severe hypoxic injury, commonly occurring because of arteriosclerosis, blockage of major
arteries, particularly lower leg
o Subsequent bacterial invasion causes the tissues to undergo necrosis
 Dry gangrene- dry skin shrinks, wrinkles color to dark brown
 Wet gangrene- neutrophils invade causing liquefactive necrosis
 Gas gangrene- anaerobic bacteria (clostridium) causes gas bubbles. Can be fatal
Pathologic Tissue Calcification
 Calcification
o Deposits of calcium salts in body tissue
 2 types
o dystrophic Calcification
 deposits of calcium in dead tissue (TB , arterial sclerosis)
o Metastatic Calcification
 Occurs with increased blood calcium due to hyperparathyroidism (lungs, kidney, gastric mucosa)
Special Implications for the Rehabilitation Specialist
 Cell injury: Multiple Cell injuries
 Concepts in the lecture are important for understanding the pathogenesis of a variety of acute illnesses you may
see
 Our example client has a TBI with pelvic fracture develops pneumonia and pulmonary compromise and suffers MI
 TBI often occurs with a MVA damaging the brain
 What brain structures will be involved in a coup contrecoup injury?
QUESTIONS
What types of secondary injury to neural tissue may occur?
 From hypoxic/ischemic injury, increased ICP, shift or herniation of tissue
 Hematomas
What signs and symptoms may be present?
 Headache, loss of smell, obtunded consciousness, loss of consciousness
What type of integumentary or orthopedic sequel are common with MVA?
 Open wounds and fractures are common sequel of MVA
o With fracture normal blood supply is disrupted
 Osteocytes die form trauma and the resulting ischemia
 New bone forms and remodeling results
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Process can takes weeks to months depending on the type of fracture, location, vascular supply,
health and age
What will result if the myocardium is subject to ischemia for a sufficient length?
 Myocytes become irreversible injured
 A cascade of physiologic and anatomic events occur leading to death of myocardial cells (coagulative necrosis)
Signs and Symptoms correlate with stages of cell injury
 Acute MI= angina, SOB, sweating, nausea
 ECG reveals abnormalities in conductivity and if a significant percentage of the heart is involved CHF may ensue
 Enzymes (CK-MB) are released
The therapist must understand the pathologic process as client care will be determined
 Recovery form TBI tends to follow the progression of Rancho Los Amigos Level of Cognitive Function Scale
 Levels I-III primary goals
o Increase tolerance to activites, tolerate upright posture, increase interaction with environment
 Levels IV-VI
o Increasing physical and cognitive endurance
 Level VII-VIII
o Focuses on the skills necessary to reenter community
Fractures
 Following fracture
o Period of immobilization to remove longitudinal stress
o Theis allows for phagocytic removal of necrotic bone and fibrocartilaginous callus desposition
o As the fracture heals gradual progression of stress us applied
o Mobilization will depend on type of fixation and usually to persons tolerance if fixated
MI
 Highest risk of death in the hours after MI is form dysrhythmias
 Rupture of the myocardium is possible during days 3 to 10 form transmural MI
o These risk dictates that exercise during this time must not subject the individuals to excessive stress
o Mobilization soon after may decrease the likelihood of succumbing to the negative effects of bedrest
Rehabilitation Implications
 Causes of tissue damage vary and recovery can do end on type, severity and duration of the injury
 Tissue response varies depending on the ell type level of differentiation and modifying factors
o Cells have adaptive processes
o Cells can have chronic alteration and can undergo necrosis
 Rehabilitation professionals will encounter these process in the course of practice
INJURY, INFLAMMATION, AND TISSUE HEALING
TISSUE HEALING
Process of tissue Healing
 Begins soon after tissue injury or death
 Occurs by:
o Regeneration- regrowth of original tissue
o Repair- formation of connective tissue scar
 Inflammatory cells that are recruited from the blood circulation begin healing by
o Breaking down and removing necrotic tissue
 Phagocytosis
o Process is complex and in influenced by the following components
General Components of Tissue Healing
 Fibronectin
 Proteoglycans and Elastin
 Collagen
Fibronectin role in synthesis of the extracellular matrix
 Formation of a scaffold with ability to provide tensile strength and glue other substances and cells
 One of the first proteins (plasma proteins source)
 Binds to and stabilizes fibrin (protein that makes up clots) and facilitates other proteins phagocytosis
 Attracts fibroblast and macrophages by chemotaxis which secrete more fibronectin
 Binds to proteoglycans and collagen stabilizing healing tissue
Proteoglycans and Elastins role in synthesis of the extracellular matrix
 Proteoglycans
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Contain carb chains and sugars
Fibroblasts are the source
Binds to fibronectin & collagen for stabilization
Hold water and hydrate tissue
After tissue is healed
 Contribute to organization and stability of collagen and provide the basement membrane with
electrical properties
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Elastin
o Fibroblasts are the source
o Becomes cross linked to form fibrils or sheets that provide tissue elasticity
Collagen
 Most important for structural support and tensile strength
 Fibrous protein, 3 chains of amino acids coiled into triple helix
 More than 18 types
 Organization and composition indicate function (table 6-2)
o Random- flexibility, rigidity
o Right angles- transmission of light (eyes)
o Tubular- elasticity
o Thicker- allows cross linking
 Types of Collagen
o Type I: mature scar, tendons and bones
o Type 2: hyaline cartilage (end of nose and ears)
o Type3: predominantly in vascular structures, seen in fresh scars
Phases of Healing
 Well defined
 Overlap
 Can take months to years to complete
o Hemostasis and degeneration
o Inflammation
o Proliferation and migration
o Remodeling and maturation
Hemostasis and Degeneration
 Hemostasis is 1st step
o Body tries to stop bleeding by initiating coagulation
 Blood fills gap
 Clumping of platelets
 Formation of loose clot
o Platelets release chemical messengers
 Growth factors that stimulate proliferation and migration of epithelial cells, fibroblasts and vascular
endothelial cells
 Inflammation begins as degeneration phase starts
o Formation of a hematoma
o Necrosis of dead cells
 Tissue repair begins within 24 hours with the migration of fibroblasts
 Reconstitution of extracellular matrix
 Followed by maturation and regeneration but we must look at inflammation
Inflammation
 Trauma results in a biochemical & cellular process in vascularization tissues
o Most of the essential components are found in the circulation
 Early mediators (facilitators) affect the vascular beds
 Increase movement of plasma and blood cells to tissue surrounding injury (exudate)
 Superficial hallmarks
 Redness (rubor)
 Swelling (tumor)
 Heat (calor)
 Pain (dolor)
 Loss of function (functio laeso)
o Acute- sudden onset and short duration
o Chronic- does not resolve and persists over time
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3 characteristics in microcirculation
o blood vessels dilate, increasing flow to area (can cause edema and heat on the skin)
o vascular permeability increased (outward leakage of plasma= exudate or transudate)
o white blood cells adhere to the inner wall of vessel, then migrate through the vessel to injury site
Inflammation and Repair
 can be divided into several phases
o each phase involves different biomechanical mediators and cells that function together
 destroy the injurious pathological or physical agents
 wall off and confine these agents so as to limit their effects on the host
 stimulate and enhance the healing process
 promote regeneration of normal tissue to restore function
Vascular Effects are Immediate
 Vasoconstriction
o Arterioles constrict briefly (sec to minutes)
o Reduces the blood flow
o Prevents hemorrhage
 Vasodilation: immediately follows vasoconstriction
o Increasing blood flow& pressure
 Thus exudation of plasma and blood cells into the tissues
 Transudate (little protein) vs. exudate 9includes protein)
o Leading to edema and swelling
Increased Permeability
 As plasma moves outward, blood remaining in microcirculation slows and becomes more viscous (stasis)
 Leukocytes (phagocytes) migrate to vessel walls (called margination), layer against the walls and adhere (called
pavementing)
 Biochemical mediators (histamine, prostaglandin, leukotrienes, serotonin and bradyknins) stimulate endothelial
cells to retract
 Leukocytes squeeze out through the spaces created by endothelial retraction ( called diapedesis)
 Permits passage of water, salts, and small plasma proteins to flow into the damaged area (exudate)
 Once in tissues all of these cells act togheter to stimulate and control the inflammatory process and interact with
components of the immune response
 Chemotaxis
o Guides WBC to the site of injury
(Cells that Contribute)
 Neutrophils
o 1st phagocytic leukocytes to arrive
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o leukocyte number is diagnostic
 Monocytes and macrophages
o Next phagocytes on the scene
o Perform like neutrophils but longer and later in process
 Other cells
o Eosinophils- role in control of inflammation, asthma and allergies
o Basophils- function similar to mast
o Platelets stop bleeding if vascular injury has occurred
 Inflammation is mediated by 3 key plasma [protein systems
o The complement system
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o The clotting system
o The kinin system
 All of these act at the site of tissue injury to kill microorganisms and remove the debris
 Prepares the lesion for tissue regeneration or repair and resolution
Chemical Mediators of Inflammation
 Histamine
o Mast cells, basophils, platelets
o Temporary, rapid constriction of smooth muscle, dilation of post capillary membrane and retraction of
endothelium
 Lipid Mediated Factors (membrane)
o Platelet activating factor- activation & secretion
o Leukotrienes- produce allergic and inflammatory reactions
o Prostaglandins- mediators of fever and pain
 Cytokines (metabolic, hemodynamic, hematologic)
o Interleukin 1- fever by increasing prostaglandins, reduces blood proteins
o Tissue necrosis factor- similar to IL1 (exception leukocytes)
 Blood coagulation, fibrinolytic and complement
o Plasma proteins produce chemical inflammatory mediators by preteases
o Coagulation- occurs with bleeding, fibrinogen to fibrin forms meshwork to blood clot
o Fibrinolytic- designed to dissolve these clots
o Complement- blood plasma proteins tht mediate inflammation and immunologic process with presence of
microorganisms
 Vasodilation of capillaries
 Movement of leukocytes to area
 Coasts microbes for phagocytosis
 Formation of membrane attach complex (MAC)
Functions of Acute inflammation
 3 main functions
o prevent excessive blood loss
o destroy or eliminate causative agents such as bacteria
o eliminate debris, thus allowing healing to occur
 many factors may influence the ultimate pattern of damage. Related to:
o the agent
 strength, amount, duration, nature, and invasiveness of the agent
o the host
 anatomic location of injury, host immunity, and the physiologic state of the host
Local Effects of Acute Inflammation
 Various examples of acute inflammation that you know of:
o Blister
o Hangnail
o Wound or scratch
Systemic Symptoms
 Decreased appetite
 Nausea
 Malaise
 Anemia
 Weight loss
 Weakness
Inflammatory reactions can be described in terms related to
 The duration of the process
 The pre-dominant type of exudate formed
Classification based on the pre-dominant type of exudate formed
 Exudation is a common feature of acute inflammations it may also occur during chronic reactions
 Inflammatory exudate is beneficial:
o Dilution of toxins
o Pain reduces motion
o Antibody delivery
o Other cellular components
Types of Exudate
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Serous
Fibrous
Catarrhal
Suppurative
Categorized based on type of fluid or white cells present
Mixed patterns can occur
o When seen, a comination of both names is used
 Mucopurulent
 Serofibrinous
Serous Exudate
 Thin, clear yellow or straw colored
 Contains albumin and immunoglobulins
 Early stages of most inflammations
Fibrinous Exudate
 Characterized by large amounts of fibrinogen and precipitation of fibrin masses
Catarrhal Exudate
 Considerable amounts of:
o Mucin (glycosylated proteins)
 Mucosal surfaces (nose throat)
o Leukocytes
o Occurs in inflammatory reactions that involve cells capable of mucus production
Suppurative Exudation
 Also known as purulent exudation
 Considerable amounts of pus
 Consists of a thick liquid (viscous) containing leukocytes and the debris of dead cells
Beneficial Effects of the Fluid Exudate
 Dilution of toxins
o Bacteria, allows them to be carried away in lymph
 Entry of antibodies into the extravascular space
o May lead to lysis of organisms or phagocytosis
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Transport
o Can carry antibiotics to the site where bacteria are multiplying
 Fibrin formation
o May impeded the movement of micro-organisms, trapping facilitating phagocytosis
 Delivery of nutrients and oxygen
o Essential for high metabolic activity
 Stimulation of immune response
o The drainage of exudate may stimulate the immune response
COMPLICATIONS OF INFLAMMATION
Abscess
 A circumscribed collection of pus
 Arise form infections initially
Cellulitis
 A diffuse, edematous inflammation occurring within solid tissues
Ulcer
 A lesion on the surface of the skin or a mucous membrane
 Occurs only when an inflammatory necrotic area exists on or near a surface that can be sloughed
Pseudomembranous Inflammation
 Inflammatory reaction with formation of a flase membrane composed of fibrin, necrotic epithelium and white cells
 Found only on mucous membranes in particular the pharynx, larynx, the respiratory and intestinal tracts
Adhesions
 Fibrinous exudate may bind surfaces together
PROLIFERATION AND MIGRATION STAGES OF HEALING IN CUTANEOUS WOUND HEALING
Endothelial Cell Regeneration
 Within 2 days after a skin wound or injury
o Endothelial cells of viable vessels begin to prolifereate
o Establish a circulation network to transport nutrients
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Endothelial cells bud out form the vessels
Form new capillary channels
 Neovascularization
 Angiogenesis
 Proliferative Phase
o Generally lasts form 2-3 days to 3 weeks
o Purpose is to cover and impart strength to the injury site
o 4 processes occur simultaneously
 angiogenesis
 granulation tissue formation
 wound contracture
 epithelization
o initially the walls of these capillaries are very thin, making them prone to injury
o immobilization
o excessive early motion may result in micro-hemorrhaging and increase the likelihood of infection
Angiogenesis
 new blood vessels
 directed by ischemia or chemical mediators
 buds connect to form new capillary loops
o improve nutrition and remove waste and debris
 clinically endothelial buds can be identified by tiny red dots
 as angiogenesis progresses
o dots increase in number and size
o entire capillary networks are formed
o wound bed gets pink
o lymphatic channels begin to function again
Granulation Tissue Formation
 granulation tissue= temporary lattice work of vascularized connective tissue
o fibroblast form general circulation and in the intersitiium proliferate and lay down an extracellular matrix
o matrix is composed of water and proteoglycans that fill the spaces between collagen and elastin fibers
Fibroplasia/Collagen Protection
 fibroblasts
o migrate into damaged area along with the capillaries
o lay bed of collagen to form a loose connective tissue framework
o fills defect with granulation tissue
 newly formed capillaries, fibroblasts and myofibroblasts
o provides the structure for other tissues
Wound Contraction
 extracellular matrix mediate wound contraction
 fibroblasts are transformed to myofibroblast
o drive the force of wound contraction
o actin rich myofibroblasts pull the round margins together decreasing the size
o contraction is affected by shape, depth and size of wound
Epithelialization
 as defect fills with granulation tissue epithelial cells at the wound margins multiply and migrate across the cound
bed
 keratinocytes elongate and extend pseudopods across the extracellular matrix
 they pull their parent cells with them thus re-epithelializing the wound
Remodeling and Maturation
 granulation tissue must now be strengthened and reorganized to fit the wound
o collagen synthesis continues at a rapid pace
o balance between formation and breakdown of old collagen so as not to increase scar mass
o a pink scar is still in remodeling process where as a pale resembles the surrounding tissue is fully
remodeled
 collagen fibers transform from immature Type 3 to mature type 1 and reorient along stress lines
 scars are though to mature due to both internal and external forces
o scar ties to mimin surrounding tissue
o application of forces ROM. Cross fiber massage realign fibers
 remodeling occurs for up to 2 years with greatest change in first 6-12 months
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scar tissue is at most 80% of original strength
TYPES OF WOUND CLOSURE
Healing by Primary Intention
 simplest and fastest
 clean wound whose edges are in close apposition
 most surgical wounds
 wound contracture causes minimal scar
Healing by Secondary Intention
 occurs in larger wounds or wounds complicated by infection
 more cellular debris must be removed
 more granulation tissue is formed
 larger scar is formed
 resurfacing must occur over a gap
Healing by Tertiary Intention
 combination of primary and secondary intention= delayed primary closure
 once wound is free of contamination it would be surgically closed
 typical of laceration or wounds that may have debris, they are cleaned and later closed
FACTORS AFFECTING HEALING
Blood Supply
 healing depends upon availability of healing components, nutrition and oxygen
 comprised blood supply
o results in inhibition of fibroblast migration and collagen synthesis
o decreased strength and increased infection
o tobacco and alcohol impair circulation
Infection
 affects collagen metabolism
o reducing production and increasing lysis
 encourages excessive granulation tissue formation
 in the presence of infection
o retained foreign bodies must almost always be removed (bullets, rods, & pins, implants)
Type, Size and Location of Injury
 injuries located in well-vascularized tissue heal faster
 smaller wounds heal faster
 surgical incisions heal faster
 soft tissue injuries over bones
o tend to adhere to bony surfaces
o preventing contraction and adequate opposition of the edges
Movement, Excessive Pressure
 early movement delays healing
 immobilization can result in adhesions and loss of ROM
o Has lead to the use of CPM machines for “continuous passive motion”
External Agents
 The basis for the use of modalities in physical therapeutic management of healing
o Cryotherapy (cold)
o Thermotherapy (heat)
o Ultrasound
o Electrical currents
o Manual mobilization
o Mechanical pressure
Age
 Physiological changes that occur with aging reduce the healing rate
o Childhood: wound closure occurs more rapidly
o Elders:
 Lower rate of epitheliazation
 Decreases in density and cross-linking of collagen decreases tensile strength
 Obstruction of vessels may adversely affect the whole process
Disease (Co-Morbidities)
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 Diabetes Mellitus
 Problems of circulatory system have impaired delivery of substrates and components
 Peripheral vascular compromise impairs local blood flow
 Neuropathies increase potential for trauma
 Immune-compromised patients have inadequate inflammatory responses making them more prone to infection
Nutrition
 Insufficient caloric intake
o Deficiency of amino acids, vitamins, minerals or water impairs wound healing
o Adequate protein intake
o Vitamin deficiencies
 Vitamin A required for epithelization, collagen synthesis and cross-linking
 Vitamin B1, B2 and C have all been shown to effect fibroblasts and collagen formation
 Zinc, magnesium and copper insufficiencies have all been shown to delay healing a tensile
strength
Medication
 Antibiotics
o Prevent or fight off infection, but also have toxic effects that inhibit healing
 Anti-Inflammatory medications block the inflammatory cascade
o Corticosteroids impair all phases of healing
 Inhibit production of prostaglandin
 Decrease margination, migration and epithealialization
 Inhibit wound contracture and decrease tensile strength
o NSAIDs
 Ibuprofen inhibits production of prostaglandins
 Cause vasoconstriction
Abnormal Wound Healing
 Absence of inflammation
 Chronic inflammation
 Hypo-granulation
 Hyper-granulation
 Hypertrophic scarring
 Keloids
 Contractures
 Dehiscence
Summary
 Inflammation is a coordinated process of body to tissues to cell injury and death
 Healing and repair depends on a number of factors
 Some beneficial others detrimental
 Rehab specialists may help with process
THE IMMUNE SYSTEM
Introduction
 viruses, bacteria, fungi, and parasites
 organisms called pathogens are responsible for disease
o viruses spend most of there time inside cells
o bacteria multiply in interstitial fluids and
o parasites burrow through organs
 without an effective immune system, we are at risk
 not all immune system responses are helpful
 excessive or inappropriate activity
Immunology
 the study of physiologic mechanisms that allow the body to recognize materials as foreign and to neutralize or
eliminate them
 the basis of immunity depends on the immune cells ability to distinguish “self” from non self”
o all cells contain specific cell surface markers
o the immune system recognizes these markers as “self” and Produces self-tolerance
Non Specific Defenses
 refers to 2 nonspecific “first lines of defense” against pathogens
o the skin and its mucosal barriers
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o the nonspecific inflammatory response
stimulated by penetration of the epithelial surface of the skin, respiratory, gastrointestinal or genitourinary tract
results in multitude of secretions which produce an unfavorable environment
o pH
o phagocytes and killer cells themselves which attach and destroy virus-infected cells and tumors
The immune system is the 3rd line of defense against Infection


*** Know the cell types in the diagram above
STEPS
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
When an injurious chemical, foreign body or micro-organism penetrates the defenses, the body attempts to
eliminate it by mechanical clearance
o Sloughed off with skin
o Caught in respiratory mucus and coughed up
o Vomited form the stomach
o Flushed by urine form the urinary tract or by fecal material form the colon
 All these defenses are both external and non-specific and protect the host as needed
Specific Resistance Immune Response
 The immune response is the body’s reaction to antigenic challenge
 Primary role of the immune system
o To recognize and destroy foreign substances
o To prevent the proliferation of mutant cells
 Characterized by specificity and memory
o When pathogen gains entrance the body produces a specific response
o Body has memory so that if the same organism is encountered again the body responds more rapidly
Acquired Immunity Responses
 2 types
o humeral (immunoglobin related) (fluid)
o cell mediated immunity (T-Cell)
 work together
 proliferation of antigen specific B and T cells which occurs when they bind to an antigen
 T cells and B cells need to migrate in the body to increase the chance of encountering a particular antigen
 Specific resistance or immunity is provided by lymphocytes (T cells and B cells)
o T Cell= cel mediated
 Our defense against abnormal cells and pathogens inside cells
 Cytotoxic T, Helper T & Suppressor T
o B Cell= antibody mediated
 Defesne against antigens and pathogens in body fluids
 Can differentiate into plasma cells which are responsible for antibodies (immunoglobin) formation
Antigen
 Any foreign substance
o “non self” in the body
o does not have marker
o capable of immunity response
o epitope that evokes response
Porpreties of Immunity
 Specificty
o A specific defense is activated by an antigen and the response targets that antigen and no others
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
Versatility
o In the course of ta lifetime an individual encounters tens of thousands of antigens and the immune system
can differentiate each
 Memory
o Remembers antigens so second exposure is stronger
 Tolerance
o Exists when immune system does not respond to antigen
T Cells and Cell-Mediated Immunity
 Initaiation, maintanence and control of immune response
 Activated by exposure to an antigen with in 24-48 hours
 Capacble of being sensitized to and recognize specific antigens on cell surface which they can then attack directly
 5 types of mature T-Cells
o Helper T cells
o Suppressor T Cell
o Memory cells
o Cytotoxic cells
o Lymphokine-producing cells
Initial Response
 Antigen presenting cells
o Promotes development and differentiation of T, B, and Hemtopoietic cells
Antigen Presentaiton
 T cells recognize antigens bound to glycoproteins in cell membrane
o Antigen-glycoprotein comination is capable of activating T cells and appears in the membrane
o Structure of glycoprotein is genetically determined in chromosome 6 in a region called the major
histocompatibility complex (MHC)
T Cells
 Learn to discriminate form self non slef
 Responsible for rejection of transplanted tissues and some auto-immune diseases
 Basis for many skin test
o Ex: TB
 HIV and AIDs compromise the vell mediated immunity with progressive deterioration of cells
 Types
o Helper T (75%)
 Stimulate the response of both B & T cells
 Activate macrophage
o
Cytotoxic T Cells: natural killer
 Directly attack and killer invaders
 Reupture, secretion and apoptosis
 Responsible for cell-mediated destruction of tumor cells and virally infected cells
o Suppressor T: cells suppress both T helper and Cytotoxic
 Reduce immune response
 Turning immune response on and off
o Memory T
 Assure that their will not be delay if antigen returns
B-Cells and Antibody-Mediated Immunity (Humeral)
 Found in different body fluids
o Salvia, blood, or vaginal secretions
 Antibodies produced by B Lymphocytes are effective against organism that are free floating (antigens)
 Types
o B Lymphocytes
 Have large quantities of surface immunoglobulins
 Initial immune response by B Cells
 An antigen enters the body
o Transported to lymph or spleen in blood stream
o After contact they trasnofrm into an antibody secreting plasma cell via a series of
intermediate proliferation and maturation phases
Effector Mechanism
 The B cell system ensures humeral immunity using antibodies as its defensive weapons
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
Together with the complement system theses antibodies destroy cells
Depending on the antigen the B cell system may be aided by
o Macrophages and/or mast cells
Antibodies
 Protein molecule, an immune-globin, produced in response to the antigen
 Interact only with the antigen that induced their synthesis (lock and key)
 Antigens combine with antibodies to elicit the maturation and activation of 2 types of lymphocytes
o B-Lymphocytes (B-Cells)
o T-Lymphocytes (T-Cells)
 Functions
o Neutralize bacterial toxins
o Neutralize viruses
o Promoting phagocytosis of bacteria activating components of the inflammatory response
 Direct effect on antigen
o Produce agglutination, precipitation or neutralization
 Indirect effects on antigen
o Activation of the complement cascade
o Recognition and binding to receptors on inflammatory cells
Know these antibodies
Consequences of Antigen-Antibody Binding
 Antigen-Antibody Complex: formed when an antibody binds to an antigen it recognizes
o There is affinity: a measure of binding strength
o Causes Agglutination: antibodies cause antigens (microbes) to clump together
 IgM is more effective than IgG
 Hemagglutination: agglutination of red blood cells used to determine ABO blood types and to
detect influenza and measles vviruses
o Opsonization: antigen is covered with antibodies that enhances its ingestion and lysis by phagocytic cells
Factors Effecting Immunity
 Nutritional status
 Medications esp. the cancer chemo-therapeutic agents
 Surgery and anesthia suppress immunity
 Burns
 Stress, psychological well being and socioeconomic status are being research
Effect of Aging
 Immune dysregulation and immune function declines with advancing age
o The thymus atrophies beginning at puberty
o Practically disappears in adulthood
 By age 45 thymus is on 5-15% its max size
o No thymic hormone is detected by age 60
 T Cell function declines (although the numbers do not)
 Those older than 60 years have
o Decreased hypersensitivity responses
o Decreased T cell mediated responses to infections
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o Decreased T Cell activity
Pediatrics & Immune Function
 Maternal antibodies provide protection within the fetal circulation
 Human infants are immunologically immature when born
o Deficiencies in antibody production
o Phagocytic activity’s, and complement activity
 At birth, total IgG levels are near adult levels
 After birth, antibody titers drop as maternal antibody is catabolized reaching a min at 5-6 months
 Recurrent respiratory tract infections are common during this period of immune insufficiency
IMMUNE DYSFUNCTION
Immune Responses
 Alteration due to exercise
 Exaggerated responses against environmental antigens (allergy)
 Under active: immunodeficiency
 Misdirected against the host’s own cells
 Directed against beneficial foreign tissues
 All of theses can be serious or life threatening
Exercise Immunology
 Depending on intensity
o Moderate= enhance
o Strenuous= depresses
 Effect on Neutrophils & Macrophages
o Rise in #
 Greater with eccentric component
o If exercise > 30 minutes a 2nd rise occurs for 2-4 hours
 Probably form cortisol
o Baseline level return
 Gentle exercise- soon returns
 Strenuous- 24 hours
 Exercise and NK cells
o NK enhancement
 Epinephrine and cytokines
o Falls off once fitness level is reached
o May be cumulative adverse effect in athletes who induce these changes several times per week
 Effects on Lymphocytes
o Brisk Exercise
 Increase WBC count in proportion to effort
o Result of mechanical effects
 Increased cardiac output
 Surge in serum epinephrine
o May be recruited form to circulation form other tissue pools with exercise
 Spleen, lymph nodes, GI Tract
o Return to baseline
 Reduced after exercise
 Effects on Cytokines
o Damage enough tissue to evoke actor inflammatory response
o Can activate
 Pro-inflammatory and exercise cytokines
 Exercise and Apoptosis
o Remove damaged cells with inflammatory response
o Failure to activate
 May result in cancer and certain viral infections
What are the implications of exercise and the immune response for the therapist
 Therapist exercise patients of all ages with a variety of clinical problems
o Lifetime of moderate exercise can be preventative
o Aged adults lose immune capability
 Evaluate client after exercise for perceived intensity
o Exercise in presence of acute viral or bacterial infection
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

If manifesting symptoms
Neck check
Fever, aching, muscles, diarrhea= contraindication
Immunodeficiency
 Immune response is absent or depressed
o Due to primary or secondary
 Primary= congenital (rare)
 Secondary- underlying disease or factor that blocks immune
 Failure can result in over whelming infection or malignant disease or both
Iatrogenic Immunodeficiency
 Induced by immunosuppressive drugs, radiation therapy or spleen removal
o Cytotoxic and immunosuppressive drugs
 Corticosteroids- anti inflammatory
 Cyclosporine- depresses immune response
o Radiation
Acquired Immunodeficiency Syndrome (AIDS)
Overview
 Disease caused by the retrovirus human immune-deficiency virus (HIV)
 Characterized by profound immunosuppression
o Leads to opportunistic infections (infections that if you were healthy you would have fought off)
o Secondary neoplasms
o Neurologic manifestations
Incidence & Epidemiology
 As of the end of 2009 2.5 million newly infected individuals worldwide including 700,000
 New infections in US have declined to 40,000/year
 In US greatest impact
o IDU- intravenous drug users
o Sex Workers
o MSM- men sleeping with men
 Age 20-49
Etiologic Factors
 Transmission
o Sexual transmission (75%)
 Heterosexual has out paced homosexual
o Viral transmission
 Direct inoculation into blood vessels breached by trauma
 Into T Helper cells
o Parenteral
o Transfusions
o Mother to infant
Pathogenesis
 HIV is a retrovirus that predominantly effects human T4 helper lymphocytes
o Binds to target cell and injects core proteins and 2 strands of RNA into cells so it can replicate now or later
 Clinical latency
o Can hide and become essentially undetectable in the blood, but contribute to destroy the CD4 cells (THelper cells) in the lymph nodes
o Only HIV antibodies remain in the serum
 The virus continues the progressive destruction
o T Cell mediated immunity & changes in humeral immunity
 When virus kills sufficient cells, it reenters the blood and the clinically apparent disease presents as AIDS
 Ends with a severely immunocompromised system susceptible to invasion by any number of infections and
carcinogenic agents
 Loss of immune function allows opportunistic infections to develop
AIDs Involvement
 Infections include
o Pnemonia carinii
o Kaposi sarcoma
 Autoimmune
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o RA
Neurological Dysfunction
o Dementia
o Encephalopathy
o Peripheral neuropathies
Medical Management
 Prevention
o Education
o Reduction/eliminate risky behavior
 Diagnosis
o ELISA- reveals HIV antibodies, western blot, indirect immunofluorescent assay
 Treatment
o No cure
o Working on vaccine
o Medical management
 HAART
 Prognosis
o Combination therapy is extending lives
Therapist Implications
 Prevention of transmission
o Greater risk in wound healing capacity
 Standard Precautions
o Use protective barriers
o Washing hands and skin
o Prevent needle sticks
o Ventilation
o Don’t treat with open wounds
o Pg precautions
o If exposed evaluate source and begin post exposure
HIV and Rehab Therapy
 HIV is considered chronic illness rather than terminal illness
 Exercise
o Safe for HIVE infected
o Pain relief, reduction of stress, atrophy, and improved function, enhanced immune function
o Moderate aerobic exercise
o Programs may increase strength
o Strength training
o ADL
o Home programs
o Modalities
Chronic Fatigue & Immune Dysfunction Syndrome
 CFIDS
 CFS
 CEBV
 Myalgic Encephaly
 Yuppie-Flu
 Several factors related to fatigue greater than 6 months (a combo of factors)
Incidence, Risk, Etiology
 200 per 100,000
 affects all ethnic groups and genders equally
 interaction of multicasual variables
o biological social behavioral
 hypothesis
o presence of chronic infection
o thyroid implications
 research findings see immune and neuroendocrine changes
 Clinical manifestations
o Sore throat, fever, muscle pain and weakness
o Prolonged lasting fatigue >6 months

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o Severity varies
o Neutrally mediated hypotension
 Medical Management
o Dx: no single test, antibodies to EBV
o RX: individual, meds, immuonglobin, nutraceticals
o Prognosis: outcomes varies
 1/3 of adults improve within 5 years
 recovered individuals have intermittent symptoms
What are the rehab Implications
 Treated following guideline and protocols for autoimmune disorders
o Pacing: energy conservation physiologic quieting stress management and balance activities
 CAREFULLY CONTROLLED GRADED EXERCISE
o Regular moderate exercise
o Flair ups- not able to exercise begin with low level intermittent activity
o Soft tissue and jt mobilization and stretching
 Monitor vitals
o RPE, heart, respiration
Hypersensitivity Disorders
 Over reaction to a substance, or hypersensitivity, is referred to as an allergic response
 Hypersensitivity designates an increased immune response to the presence of an antigen that results in tissue
destruction
 4 Types
o Type 1: IgE mediated allergic reactions
o Type2: when bodies own tissue is recognized as foreign
o Type 3: immune-complex-mediated reactions
o Type 4: cell mediated reactions
 Reactions can be immediate or delayed
o Immediate: occur in minutes to a few hours
o Delayed: may take several hours and are at max severity days after re-exposure to the antigen
Type 1 Hypersensitivity
 Immediate hypersensitivity, allergic disorders, anaphylaxis
 Hay fevers, allergic rhinitis, urticarial, asthma, and anaphylactic shock
o Characterized by production of antigen-specific IgE by B cells
o Requires repeated exposure so person is sensitized
o When IgE meets the pathogen, histamine is released with other inflammatory factors

constriction


Immediate Hypersensitivity
 Allergic disorders, anaphylaxis
o Wheezing, hypotension, swelling, urticarial, rhinnorhhea
o If response becomes systemic develops vasodilation, bronchospasm, increased mucous secretion and
edema
Type 2 Hyoersensitivity
 Cytotoxic reactions to self-antigens
 When the bodys own tissue is not recognized as “self” or is recognized as foreign
 Activation of complement
o Aggulation cell destruction and phagocytosis of cells
 Especially common for blood cells and platelets
 Examples: blood transfusion reaction
 Cross reaction of exogenous pathogen with endogenous pathogens
o Rheumatic fever- develops 2-3 weeks after strep infection can involve the heart skin and joints
o Guillain-Barre: immune response to foreign antigens but miss target and damage host nerve tissue (nodes
of Ranvier) causing paralysis
Type 3 Hypersensitivity
 Immune complex mediated reactions
 Immune complexes (antibody-antigen) are not cleared form the body and deposit in tissues around vessels
 Causes acute inflammation and local tissue injury
 Vasculitis
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o Skin, synovial joints, kidney, pleura, and pericardium
SLE (Lupis)
o Antigen of individuals own nuclei and antinuclear antibody (ANA) and deposit in skin, joints and kidney
Type 4 Hypersensitivity
 Cell Mediated Immunity
 Delayed hypersensitivity response after sensitization to an allergen
o Cosmetic, adhesive, topical med, poison ivy
 Antigen is processed by macrophages and presented to T Cells
 Example: graft rejection, latex sensitivity
 Fibromyalgia chronic muscle pain syndrome which is widespread in at least 11 of 18 tender points
 Biologic disorder associated with neurohormonal dysfunction of the ANS
o Commonly associated with hypothyroid, RA, SLE< CFS
o Systemic problem with localized myofascial pain
 Perpetuating and initiating factors
o Psychological stress, primary sleep disorder inflammatory RA, acute febrile illness
 Reciprocal relationship between immune and sleep wake systems





Incidence
o 6 million americans> RA
o women>men
o 14-68 years
Risk factors
o Prolonged anxiety, emotional stress, trauma
o Rapid steroid withdrawal, hypothyroid, viral and non viral infections, anxiety, depression
Pathogenesis
o Both central and peripheral
 Hypothalamic pituitary axis
 ANS
 Reproductive hormonal axis
 Immune system
Medical Management
o Dx: no definitive test
 Widespread pain in 4 quadrants> 3 months
 Subjective report with palpation in 11 of 18 sites
o Rx: metabolic rehab, holistic, and multidisciplinary
 Education, stress management, work simplification, meds, modalities for pain
o Prognosis: symptoms usually remain unchanged
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
Rehab Implications
o Accurate assessment (tender points)
o Direct individuals to reach goals of lessening pain, fatigue, and sleep problems
o Outcomes using scales
o Monitor vitals
o Modalities
o Exercise
 Cardio
 Variability
Summary
 Immune dysfunction can potentially impact the rehab setting in a variety of ways including direct involvement of the
system and as a comorbidity
ONCOLOGY
Cancer
 Uncontrollable cellular proliferation
 Interchangeable terms:
o Tumor
o Malignancy
o Neoplasm
o Carcinoma
 According to American Cancer Society
o 5% of cancer is genetic
o 95% is related to other (often modifiable) factors
Definitions
 Differentiation
o Process by which normal cells undergo physical and structural changes as they develop to form different
tissues on the body
 Dysplasia
o Disorganization of cells in which an adult cell varues from its normal size shape or organization
 Metaplasia
o The first level of dysplasia (early) on adult cell changes from one type to another
 Hyperplasia
o Increase in the number of cells resulting in increased tissue mass
 Tumors
o Abnormal growths of new tissue that serve no useful purpose and may home the host organism
Who gets cancer?
 The American Cancer Society
o 1.4 million new cases of invasive cancer in US
o 565,000 cancer related deaths
 1 in 3 persons will be diagnosed with some form of invasive cancer in their lifetime and 3 of 5 will
be cured and/or survive 5 years after cancer treatment
 2nd leading cause of death in the US, only exceeded by heart disease
 there are at least 3 reasons
o improved diagnostics
o computers allow us to gather and analyze statistics
o longer life span with older adults at higher risks
How Does Cancer Grow?
 Body cells, which contain DNA (except RBC)
 DNA controls the process of cell division and growth
 Cancer cells grow without control
 Tumor can interfere with normal function
 Not all tumors are cancerous
 Ability to spread distinguishes cancer
 May take years to develop
What causes cancer?
 Genetic
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
Abnormalities in biochemistry of the DNA
o Genes with abnormalities or mutations that results in inappropriate activity are termed “oncogenes”
 Abnormalities result from
o Inherited genetic alterations
o Time
o Exposure
o Some viruses
o Diet
Family History
 Genetically some families have higher risk
o EX:
 Women who inherit a mutation in breast cancer gene 1 (BRCA 1) are at increased risk for breast
cancer and for ovarian cancer
o By age 70
 87% of these women will develop breast cancer
 44% will develop ovarian cancer
o Genetic inheritance
 accounts for 5% to 10% of all breast cancer
Environment
 approximately 2/3 of all cancer are believed to be caused by some type of environmental factor
o this link could help with prevention
Role of Immune System
 when normal cells turn into cancer cells
o antigens on their surface change and are shed into the circulatory system
 patrolling cells (cytotoxic T Cells and macrophages) of the immune system provide continuous body wide
surveillance, catching and eliminating cells that undergo malignant transformation
 tumors develop when this immune surveillance breaks down or is overwhelmed
PATHOGENESIS OF CANCER
What Do Cancer Cells Do?
 Create Havoc in many ways
o Often replace normal functioning tissues
 Brain cancer- destroys normal brain functioning, may result in seizures, paralyses and eventual
death
 Produce chemicals that interfere with the body
o Tumors can secrete chemicals that can cause a host of changes in body chemistry
 Small-cell lung cancer that typically occurs in smokers
What Does Cancer Look Like?
 CAT scan or mammogram can find it
 Definitiviely diagnosed by histological exam
 Cancer cells
o Size variation
o Stain variations
o Some DNA looks distorted and smeared
 A biopsy is needed to get a sample of tissue to examine under the microscope
o Excisional biopsy
 Tumor is removed/sectioned/stained
o Fine needle aspiration
 Sliver of tissue is removed with fine needle
CLASSIFICATION SCHEMES
Tumors/Neoplasms
 New growths
o Benign or malignant
 Abnormal growth of new tissue
o Serves no useful purpose
o May harm the host organism
 Competing for vital blood supply and nutrients
 First Degree Tumor
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o Arises from cells that are normally local to structure
Second Degree Tumor
o Metastasized from another part of the body
Classification of Neoplasm
 Cell type
 Tissue of origin
 Degree of differentiation
 Anatomic site
 Whether it is benign or malignant

Benign/Malignant
 Benign Tumors
o Usually considered harmless
o Can become large enough to impair normal body functions
 Malignant Tumors
o Differ from benign
 Invade and infiltrate surrounding tissues
 Metastasize or spread form the primary site to other locations in the body
Tumor Classification by Cell Type
 Named from the tissue it arises in
o Carcinoma is applied to epithelial cancers
o Sarcoma refers to those of mesenchymal origin
 5 major classifications of normal tissue
o epithelial
o connective and muscle
o nerve
o lymphoid
o hematopoietic tissue
Epithelium
 covers all external body surfaces and lines all internal spaces and cavities
o skin, mucous membranes, GI tract, and lining of bladder
 functions
o protect, excrete, and absorb
 cancer originating in any epithelial tissues is called a carcinoma
o tumors derived from epithelial and glandular tissues are called adenocarcinoma
Connective Tissue
 consists of elastic, fibrous, and collagenous tissues, such as bone, cartilage, and fat
 benign growths are named with “-oma”
o fibroma, lipoma, chondroma, osteoma
 malignant cancers originating in connective tissue and muscle are called “-sarcomas”
o fibrosarcoma, chondrasarcoma, osteogenic sarcoma, liposarcoma, myosarcoma
Nerve Tissue
 brain, spinal cord, and nerves
o consists of neurons, nerve fibers, dendrites, and a supporting tissue composed of glial cells
 tumors arising in nerve tissue are named for the type of cell involved
o tumors arising from astrocytes (glial cells) thought to form BBB, are called astrocytomas
 tumors are often benign
o because of the critical location, are more likely to be harmful than benign tumors in other sites
Lymphoid Tissues
 lymph nodes, the spleen, and the intestinal lining
 referred to as lymphomas
Hemopoietic Tissues
 cancers are called leukemias
Staging
 staging is the process of describing the extent of disease at the time of diagnosis
o aid in treatment planning
o predict clinical outcome (prognosis)
o compare different treatment approaches
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TNM Classification
 American Joint Committee on Cancer
 Staged by 3 basic components
o Primary tumor (T)
o Regional lymph nodes (N)
o Metastasis (M)
 Numbers are used with each component to denote extent of involvement
TNM Staging
T
 “T” indicates the size, depth, and area of the primary tumor
 Tx: primary tumor cannot be assessed
 T0: no evidence of primary tumor
 Tis: carcinoma is situ
 T1, T2, T3, T4: progressive increase in tumor size and involvement locally
N
 “N” indicates whether the cancer has spread to regional lymph nodes
 Nx: regional lymph nodes cannot be assessed
 N0: no evidence of metastases to regional lymph nodes
 N1, N2, N3: increasing involvement of regional lymph nodes
M
 “M” notes the presence or absence of distant metastases
 Mx: distant metastases cannot be assessed
 M0: no evidence of metastasis
 M1: distant metastasis present
Once T,N,M classifications are made:
 Combined with determine the stage of the patient’s cancer
 In general, the higher the stage of disease, the lower the odds that treatment will be successful
o Stage 1: T1 N0 M0
o Stage 2: T2 N1 M0
o Stage 3: T3 N1 M1
Grading
 Classifies the degree of malignancy and differentiation and estimates tumor growth
o Low grade tumors have cells more closely resembling normal cells
 Grade 1:
 Grade 2:
o High-grade tumors has poorly differentiated cells (don’t look like the original cell)
 Grade 3:
 Grade 4:
Invasion and Metastasis
 Tumors can spread throughout the body in several ways
o Local spread by direct invasion to contiguous organs
o Metastases to distant organs by lymphatics and veins
o Metastases by implantation
Local Spread
 Local invasion may occur as a function of direct tumor extension
 Cells or clumps of cells detach form the primary tumor and invade the surrounding interstitial spaces
 Mechanisms thought to eb important in local invasion include
o Cellular multiplication
o Mechanical pressure
o Release of lytic enzymes
o Decreased cell-to-cell adhesion (cancer cells slippery)
o Increased motility of individual tumor cells
Cellular Multiplication
 Invasion depends on the rate of cellular multiplication, which is a function of
o Cell generation time
o Number of cells dividing
o Cell loss from tumor
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Mechanical Invasion
 Invasion related to mechanical pressure
 Pressure form the growing mass blocks local blood vessels, leading to local tissue death and a reduced
mechanical resistance that further aids the spread
Lytic Enzymes
 Many tumors secrete lytic enzymes and normal tissue adjacent to ares of tumor invasion show considerable lytic
damage
o Collagenous
o Proteases
o Plasminogen activator
Decreased Cell Adhesion
 Cancer cells do not adhere to one another as well as normal cells
 This slippery trait has been related to fibronectin
o Regulates cell attachment, spreading, phagocytosis, and cell structure effects
o Stimulates cell movement and generally acts as an anchoring molecule
 Cancer cells may make a defective type of fibronectin or they may break it down
 Low levels or loss of this fibronectin may help cancer cells slip between normal cells
Increased Motility
 The invasion process
o Detachment and subsequent infiltration of cells into adjacent tissue
o The migration of cells through the vascular wall into the circulation (intravasation)
o Movement out of the vascular wall (extravasation) into a secondary site
 Tumor cells
o Move under their own power by chemotactic factors
o Acquires independent and continuous stimulation of its motile behavior, which is necessary for invasion
Metastasis
 Spread of tumor cells form a primary site of origin to a distant site
 STEPS
o Direct or continuous extension of local invasion
o Penetration into lymphatics, blood vessels, or body cavities
o Release into lymph or blood
o Transport to secondary sites
o Entry and growth in secondary sites
 5 most common
o lymph nodes
o liver
o lung
o bone
o brain
 spread may be negatively influenced by
o aging or dysfunctional immune system
o hormonal environment
o pregnancy, and stress
 factors that may slow the spread of metastasis
o radiation & chemotherapy
o anticoagulants, steroids, and other anti-inflammatory agents
Mechanisms of Metastasis
 Metastatic Cascade
 1° tumor
o local invasion
o angiogenesis
o tumor cells invade host blood vessels and are discharged into the venous drainage
o rapidly growing tumors’
 millions of tumor cells can be shed into the circulation every day
 only a small percentage of circulating tumor cells initiate metastatic colonies
o most cells released into bloodstream are quickly eliminated
Incidence of Metastasis
 30% of all clients with newly diagnosed cancers have clinically detectable metastases
 even metastases have the potential to metastasize
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
size variation and anatomic location of metastases
o can make complete surgical removal of disease impossible
Clinical Manifestations of Metastasis
 spread may occur as late as 15 to 20 years after initial diagnosis and treatment
o thorough past medical history
 metastases most commonly observed in a therapy practice
o the pulmonary system
o the hepatic system
o the skeletal system
o the CNS system
Pulmonary System
 pulmonary metastases
o most common
o venous drainage to the superior and inferior vena cava make the lungs the first organ to filter malignant
cells
 asymptomatic until tumor cells have obstructed bronchi or have expanded and reached the parietal pleura
o pain
o dyspnea
 lung cancer is the most common primary tumor to metastasize to the brain
Hepatic System
 lever metastases are among the most ominous signs of advanced cancer
o liver filters blood coming in from the GI tract making it a 1 metastatic site for tumors
 stomach, colorectum, and pancreas
 symptoms include abdominal pain and tenderness with general malaise and fatigue
Skeletal System
 Bone Metastases
o Can be initial site of metastatic disease
o Generally indicate a poor prognosis
o Pain
o Lung, breast, and prostate
 Responsible for most metastatic bone disease
 Tumors of the thyroid and kidney
 Lymphoma and melanoma
 Types
o Osteolytic type
 Marked by areas of decreased bone density
o Osteoblastic
 Areas of dense scarring and increased bone density
 Pain
o Deep and worsened by activity especially with bearing
 Disabling pathologic factors
o Especially long bones in up to half of people with osteolytic metastases
 Involvement of the vertebrae
o May result in epidural spinal cord compression
o Resultant quadriplegia or paraplegia, death
 Primary bone tumors, such as osteogenic sarcoma, metastasize initially to the lungs
Central Nervous System
 Many primary tumors may lead to CNS metastases
o Lung carcinomas (50%)
o Breast carcinoma (15%)
 Metastatic disease in the brain is life-threatening and emotionally debilitating
o Increase intracranial pressure
o Obstruct the normal flow of CSF
o Change mentation
o Reduce sensory and motor function
 Primary tumors rarely develop metastases outside the CNS
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CLINICAL MANIFESTATIONS FOR CANCER
Clinical Manifestation
 Most cancers in their earliest, most treatable stages are asymptomatic
 Later, the rapid growth encroaches on healthy tissue, causing destruction, necrosis, ulceration, and hemorrhage
and producing local and systemic effects
Pain
 Usually kittle or no pain early
 Pain occurs in >1/2 of patietnes who are terminally ill
 Influenced by
o Fear, anxiety, loss of sleep, fatigue and overall physical deterioration
 General mechanisms
o Pressure, obstruction, invasion of sensitive structures, stretching of visceral surfaces, tissue destruction
and inflammation
Cancer Pain Syndrome
 Common
 Cause:
o Multifaceted
o Depend on the tissue structure as well as on the mechanisms involved
 Some pain is caused by pressure on nerves or by the displacement of nerves
 Pain may also result from interference with blood supply or from blockage within hollow organs
 Bone mets common cause
o Mild to intense with weight bearing, pathologic fx
 Mild to moderate superficial pain
o Signs and symptoms accompanying may produce a sympathetic response which may include
 Hypertension
 Tachycardia
 Tachypnea
 Severe or Visceral Pain
o A parasympathetic response is more characteristic with:
 Hypotension
 Bradycardia
 Nausea
 Vomiting
 Tachypnea
 Weakness
 Fainting
Other Clinical Manifestations include
 Addiction
 Fatigue
 Cachexia
 Anemia
 Infection
ETIOLOGY OF CANCER
Etiology
 Endogenous (genetic) origin
 Exogenous (environmental or external) origin
 Result of multiple environmental, viral, and genetic agents working together to disrupt the immune system
 Certain cancers show a familial pattern giving people a hereditary predisposition to cancer
Cancer and Aging
 Age is the single most significant risk factor for cancer
 Cancer is the 2nd most common cause of mortality in the elderly
 Cancer incidence and mortality rates increase with age until the 84th year when they plateau
 Exposed to carcinogens longer than younger people
 Effects of age on immune function and host defense
 Aging cells, when copying their genetic material, may begin to err, giving rise to mutations
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Risk Factors
 Race
 Geographic location
 Precancerous lesions
 Stress
 Personal behaviors
 Diet
 Alcohol consumption
 Sexual/reproductive behaviors
CANCER TREATMENT
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Chemotherapy
Radiation
Surgery
Immunotherapy
CANCER AND EXERCISE
As a Prevention Strategy
 Level of physical activity in which an individual engages may affect cancer risk
 The intensity, duration, and frequency specifically designed to improve physical fitness
 A role for exercise in specifically reducing cancer risk has been conjectured and is referred to as the exercisecancer hypothesis
For person with Cancer
 Generalized weakness associated with treatment can be more debilitating that the disease itself
 Strength and cardiovascular training, is an essential component for may people with cancer
 Not all people with cancer are able to participate in aerobic exercise
Contraindications for Exercise
 Bone marrow suppression is a common and serious side effect of many chemotherapeutic agents and can be a
side effect of radiation therapy in some instances
 Therefore it is extremely important to monitor the hematologic values
 Counts
o Platelet count < 50,000 microL
o Hemoglobin <10 g/dL
o WBC <3000 microL
o Absolute granulocytes <2500 microL
Monitoring
 Monitor
o Pulse rate, breathing frequency, blood pressure, and signs/symptoms such as pallor and sweating
throughout
 Watch closely for early signs
o Dyspnea, pallor, sweating, fatigue of cardiopulmonary complications of cancer treatment
 The activity level of someone with anemia also may require adjustment may have elevated pulse and respiratory
rates because of hypoxia
 Person may become easily fatigued with minimal exertion; interval exercise or a bedside exercise program should
be performed during frequent but short sessions
Exercise Intensity
 Determined by training heart rate may be difficult
o Inappropriate heart responses to exercise and large physiologic changes on a day-to-day basis form
disease and treatment, including changes in medications
 Compromised skeletal integrity may prevent weight-bearing activities
o Non-weight bearing aerobic activities, which may by utilized for people with bone and joint disease
including cycling rowing and swimming
Energy-Conservation
 May be necessary for person with chronic fatigue and those whose functional status is declining
 Therapeutic exercise should be scheduled during periods when person has highest level of energy
 Interval exercise may be preferred at first, with work-rest intervals beginning at level of tolerance
o May be no more than 1 minute of exercise followed by 1 minute of rest then repeat
o As the endurance level increases the duration of work may be increased and the interval of rest decreased
Prevention
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Quit smoking or using tobacco
Limit exposure to the sun and use a sun block
Use alcohol only in moderation
Eat low-fat, high fiber diet that includes foods rich in vitamin A and C
Be aware of risk factors
Exercise and stay active
Have routine physical examinations
o Identify possible risk behaviors or problems
o Early detection of cancer
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