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%

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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