PATHOPHYSIOLOGY IWeek 1
THE IMPORTANT STUFF
Pathophysiology: Concepts of Altered Health States
Grading: Test 1 20% (March 1)Test 2 20% (March 15)Final Exam 50% (April 5)Participation 10%
My contact information:email: [email protected]: 633-1861
CONCEPTS OF HEALTH AND DISEASECHAPTER 1
From the National Museum of Health and Medicine
The flu epidemic of 1918
CONCEPTS OF HEALTH AND DISEASECHAPTER 1
Health is subjective
WHO definition of health: “a state of complete physical, mental and social well-being and not merely the absence of disease…”
Physiology refers to the body’s functions and processes
Pathology refers to changes in cells, tissues and organs that cause or are caused by disease
CONCEPTS OF HEALTH AND DISEASECHAPTER 1
There are multiple etiologies of disease:Biological Causes (bacteria, viruses)Physical Causes (trauma, injuries)Genetic Causes (congenital diseases)Chemical (alcohol)Nutritional
Most diseases are multi-factorial, having a genetic predisposition and triggered by environmental factors.
VOCABULARY
Etiology: the causes of diseasePathogenesis: the sequence of cellular events that occur to express a diseaseMorphology: the structure or form of cells and tissues
Sign: an observable manifestation of a disease (measuring a fever)Symptom: a subjective feeling associated with a disease (muscle aches)
STATISTICAL TERMS
Reliability: if the test is repeated, the same result is obtainedValidity: does the test measure what it is supposed to measure?Sensitivity: on a specific test, the percentage of people with a disease who will test positive
True positivesSpecificity: the percentage of people who do not have the disease that will test negative using that test
True negatives
EPIDEMIOLOGY
The study of disease in populations.
Incidence: the number of new cases in a given time
Prevalence: the number of people in a popluationthat have a particular disease during a given time
THE NATURAL COURSES OF DISEASE
Acute: usually severe and self-limited
Chronic: a long-term process
Subacute: intermediate, not as severe as an acute illness, but not as long as a chronic disease
Subclinical: disease is present but is not clinically detectable
EPIDEMIOLOGY
Mortality: the death rate due to a particular disease
Morbidity: the effects a disease has on a person’s life
Prognosis: the probable outcome of a disease
PREVENTION OF DISEASE
Primary preventionThe removal of risk factors before disease occurs
Secondary preventionThe early detection of disease when it is present
Tertiary preventionPreventing further progression of disease once it is present or attempting to reduce complications
CONCEPTS OF ALTERED HEALTH IN CHILDRENCHAPTER 2
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PRENATAL GROWTH AND DEVELOPMENT
Embryonic period: conception through the 8th
week. Most of organ differentiation occurs during this time.
Fetal period: begins in the 9th week, organ growth
Lung maturation is completed in the 26th-29th
weeks
INFANCY
The period from birth until 18 months of age. A period of dramatic growth and development. Problems of prematurity: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis. Potential problems at birth include respiratory and cardiovascular problems, birth injury and temperature regulation. After the neonatal period: failure to thrive, sudden infant death syndrome, injuries, infection and abuse.
EARLY CHILDHOOD
18 months until 5 years of ageSignificant development of locomotion and language occurs during this time. Children become more independent. Problems during childhood: injuries (MVAs are the most common), infection, abuse. Some development of chronic disease can occur (asthma, epilepsy) and some cancers will appear in this age range.
MIDDLE CHILDHOOD
Ages 6-12 years
Further growth and development.
Some children will enter puberty (girls usually earlier than boys).
Health problems: infections (respiratory and GI most common), injuries and accidents.
Higher incidences of cancer and chronic illnesses
ADOLESCENCE
Ages 13-19
Growth spurt before final height is reached
Changes in endocrine system, puberty
Increased risks for accidents, suicide and most deaths are from injuries
Cancer is leading cause of death not due to injuryLeukemia is leading cause of mortalityLymphoma, bone, testicular cancers also occur
ADOLESCENCE
Development of sexual activity increases the risks of STDs and pregnancy.
~40% of teenage females will become pregnant before age 20
Tobacco, alcohol and drug abuse prevalent
Poor judgment can affect control of chronic diseases like asthma and diabetes
CONCEPTS OF ALTERED HEALTH IN OLDER ADULTSCHAPTER 3
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ELDERLY
Age 65 and olderYoung old: 65-74Middle old: 75-84Old-old: 85 and up
The elderly are the largest consumers of health care in the U.S. This population has grown and is expected to continue to increase dramatically.
Aging is a combination of genetically programmed changes combined with accumulated environmental factors.
NORMAL AGING
SkinDecreased thickness of the dermisCollagen degeneration leads to decreased strength and elasticityDecreased production of sweat and sebumIncreased fragility of capillaries and blood vessels leads to easier bruising
HairDecreased thicknessIncreased coarsenessDecreased melanin production leads to graying
NORMAL AGING
MusculoskeletalDecreased height and compression of spinal columnDecreased muscle size and strengthDecreased bone mass, especially in postmenopausal femalesDecrease in lean body mass and increase in fat massDevelopment of arthritis: approximately 80% of people will have evidence of osteoarthritis by age 65
NORMAL AGING
CardiovascularArteries become stifferThickened left ventricleDecrease in maximum heart rateIncrease in systolic blood pressure compared to diastolic changesOrthostatic changes
NORMAL AGING
RespiratoryDecreased elastic recoil of lungsTotal lung capacity the same, but decreased vital capacity
NeurologicalDecrease in number of neurons due to atrophyNeural dysfunction causes slower processingDecreased reaction time and reflexesDecreased senses: vision, hearing, smell, tasteIncrease in falls and instability: 20% mortality rate in first year after a hip fracture
NORMAL AGING
Immune systemDecrease in immune function with increased susceptibility to infectionDecrease in normal immune responses (fever, white blood cell counts)Increase in auto-antibodies
GastrointestinalDry mouthDecrease in gastric secretions, B12 deficiencyConstipationDiverticula
NORMAL AGING
RenalDecrease in glomerular filtration rateDecrease in medication clearances
GenitourinaryDecreased bladder emptying Decrease in force of urinary streamBenign prostatic hypertrophy
COMMON PROBLEMS OF THE ELDERLY
Decline in vision and hearing
Osteoarthritis
Hypertension
Coronary Artery Disease
COMMON PROBLEMS OF THE ELDERLY
Instability and falls
Hip fractures are significant cause of morbidity in the elderly and results in over $12 billion in healthcare costs in the United States
50% of adults will be in a nursing home for at least one year and 20% of patients will die in the year following a hip fracture
COMMON PROBLEMS IN THE ELDERLY
Depression: symptoms estimated 15% in the community, higher in nursing home
Suicide risk increases as age increases
Suicide rates in the elderly are higher than in the general population
COMMON PROBLEMS IN THE ELDERLY
Dementia: acquired persistent impairmentAffects memory, language, cognition, etc.Multiple causes: degenerative, vascular, infectious, toxic, metabolic
Delirium: acute confusional state Develops over hours to days, worse at nightCan happen in acute illnesses: UTI, pneumonia, MIHigh mortality rate (20-40%)
CELLULAR ADAPTATION, INJURY, AND DEATHCHAPTER 5
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CELLULAR ADAPTION
Cells can adapt to stresses to try and maintain normal function.
Adaptive changes include:AtrophyHypertrophyHyperplasiaMetaplasiaDysplasia
ATROPHY
Occurs due to stress or a decrease in work demands. Decreased cell size, function and oxygen consumptionPotential causes:
Disuse (cast)Denervation (paralysis)Decline in endocrine stimulation (postmenopausal)Poor nutritionIschemia
HYPERTROPHY
Occurs due to stresses or increased workload
Increased cell size, function and oxygen consumption
Can be normal (enlargement of a single kidney after nephrectomy) or abnormal (hypertrophic cardiomyopathy)
HYPERTROPHY
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HYPERPLASIA
Increase in the number of cells
Only occurs in tissues whose cells divide (not in nerves, skeletal or cardiac muscle)
Two types:Hormonal (breast and uterine enlargement in pregnancy)Compensatory (liver after partial hepatectomy)
May occur with hypertrophy
METAPLASIA
A reversible change from one cell type to another
Usually due to chronic irritation or inflammation
Can develop into cancerous change
DYSPLASIA
Abnormal cell growth resulting in various sizes, shapes and organization of cells.
Minor dysplasia can be caused by chronic irritation and inflammation.
Is potentially reversible if the cells recover and the inciting cause is removed, but it can lead to cancer.
INTRACELLULAR ACCUMULATIONS
Buildup of substances that the cell can’t clear
Normal substances: protein, lipids
Abnormal products made by the cell
Exogenous products: coal dust, lead
FATTY LIVER
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BLACK LUNG
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ABNORMAL CALCIFICATIONS
The accumulation of calcium salts in tissue
Dystrophic: occurs in injured tissueAtherosclerosisTuberculosisHeart valves
Metastatic: due to increased serum calciumHyperparathyroidismMetastatic cancerRenal failure
CELL INJURY AND DEATH
Cells can be damaged from multiple causes:
Physical (fractures, tears, crush injuries)Disrupts blood flow and damages cells
Temperature (burns, frostbite)Heat inactivates enzymes and disrupts cell membranescold vasoconstricts and increases viscosity
Electrical Disruption of neural and cardiac impulses, heat damage
CELL INJURY AND DEATH
Ionizing radiation:Directly kills cells, interrupts cell replication and causes genetic mutations.
Associated with skin cancer, leukemia, lung cancer
Cancer cells are rapidly dividing and are more susceptible to the effects of radiation (for treatment purposes)
Radiation treatment can lead to fibrosis and scarring
CELL INJURY AND DEATH
Chemicals
Can directly injure cell structures and membranes
Cells can be damaged by metabolites that are created during the breakdown on chemicals (carbon tetrachloride and liver cells)
Drugs can also cause direct damage or damage by metabolites (Tylenol)
CELL INJURY AND DEATH
Lead Small amounts can be toxicSources can include paint, dust, soil, contaminated root vegetables, pipes, solder, etc. At risk occupations: miners, welders, battery workers and pottery makersAbsorbed into bloodstream through the GI tract or lungs, stored mostly in bones. Inactivates enzymes, competes with calcium, interferes with nerve transmissions
CELL INJURY AND DEATH
Lead toxicity
AnemiaAbdominal painLead linesRenal failureImpaired brain development and loss of cortical cells
Lower IQ, poor school performance, neuropathyEncephalopathy: vomiting, seizures, coma
CELL INJURY AND DEATH
Lead lines on x-ray Burton’s lines
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CELL INJURY AND DEATH
Biologic agentsViruses incorporate themselves into DNABacteria can produce toxins that injure cellsLarger parasites can injure tissue and can clog the lumens of blood vessels, GI tract, etc.
MalnutritionDeficiencies in vitamins and proteins can cause tissue damage
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MECHANISMS OF CELL INJURY
Free radical formation
Hypoxia
Disruption of calcium homeostasis
FREE RADICAL INJURY
Free radicals: single unpaired electron in an outer orbitHighly unstable and can lead to chain reactions causing more free radical formationDamages cell membranes, proteins, DNA, enzymesNaturally produced during energy generation, inflammation and breakdown of lipidsBody normally uses free radicals to kill bacteriaMolecular oxygen is the main source
FREE RADICAL INJURY
Damages cells in three waysDestruction of lipids in cell membranes, leading to loss of membrane stabilityAttacks and modifies proteins, particularly in enzymesDNA: single strand breaks, cross-links and changing base pairs. If the damage is extensive, the DNA repair mechanisms may be overwhelmed
Free radical damage is more severe in cells who have been deprived of oxygen or exposed to certain chemicalsVitamins E and C are anti-oxidants
HYPOXIA
When cells are deprived of oxygenCells that use more energy (brain, heart, kidney) will be damaged faster than those who require less energyCaused by decreased oxygen supply (respiratory disease), ischemia, anemia, swelling, inability of cell to use oxygenAs cell metabolism decreases, it uses up stored glycogen, pH falls and lactic acid accumulates. Failure of Na+/K+ pump causes cellular swelling then loss of enzymes and proteins occurs
HYPOXIA
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IMPAIRED CALCIUM HOMEOSTASIS
Normal: low levels of calcium inside cell, higher levels outside cell
When cells are damaged, the pump allows more calcium inside the cell and calcium is released by intracellular organelles
Enzymes are activated that damage the cell membrane, proteins and cytoskeleton
CELL INJURY AND CELL DEATH
Injury can be reversible or lethal
Reversible changes are:Cellular swelling (usually from hypoxia)
Fatty change (from intracellular fat accumulation)More severeMostly affects liver, but also heart, kidneys
IRREVERSIBLE CELL DEATH
Apoptosis: the natural programmed cell death that rids the body of unnecessary, worn out or damaged cellsCaused by activation of enzymes that cause cell shrinkageNormally occurs in the immune system, shrinkage of breast tissue after weaningOccurs abnormally in Alzheimer’s, Parkinson’s, ALS, Hepatitis and cancer
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IRREVERSIBLE CELL DEATH
Necrosis: cell death in living tissueDue to the unregulated digestion of cells by enzymes that occurs hours after cell deathInterferes with cell replacement and tissue regenerationThree types
Liquefaction (abscess)Coagulation (infarcts)Caseous (tuberculosis)
NECROSIS
Liquefaction necrosis in a liver abscess
Caseous necrosis in the spleen
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GANGRENE
A large area of necrosis
Two types:Dry- tissue shrinks, wrinkles and turns darker colored, occurs on extremities
Wet- cold, swollen, moist, black, blistered tissue. Frequently infected with bacteria and has a foul odor
Gas- caused by bacteria called Clostridium perfringens, a bacteria that lives in soil and contaminates open wounds like compound fractures. Characterized by bubbles of hydrogen sulfide gas that is produced by the bacteria and accumulates in muscle.
GANGRENE
Dry Wet
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REVIEW
List etiologies of diseaseDifferentiate between
Sign vs. symptomSensitivity vs. specificityIncidence vs. prevalenceMorbidity vs. mortalityDelirium vs. dementia
Differentiate between periods of prenatal developmentList common problems at each stage of growthDifferentiate between normal and abnormal aging
REVIEW
List and define types of cell adaption:AtrophyHypertrophyHyperplasiaMetaplasiaDysplasia
List substances that can accumulate intracellularly
List types of calcifications and causes
REVIEW
Review mechanisms of cell injury by:Physical causesTemperature extremesElectrical injuryRadiationChemicalsBiological agentsNutritional deficiencies
REVIEW
Define free radicals and list the three ways they damage cells
Define hypoxia and its effects
Define and differentiate between reversible and irreversible cell damage
Define apoptosis and necrosis
List the different types of necrosis and gangrene and causes for each
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