Causes of Disease

Review Adaptation Ways to adapt to injury: Atrophy Hypertrophy Hyperplasia

All of these will have consequences for the tissue, organ, and system.

Hyperplasia Compensatory Hormones Pathologic Atypical

Compensatory Can’t keep up so increase in cell number (Remember adaptation to injury!) Liver damaged by byproducts of alcohol

metabolism or infection with hepatitis virus

Cells are produced. Liver cells can divide. Some are bi-nucleated.

Hormonal Stimulation Number of cells increase. Cells of follicle in ovary increase in

response to FSH Endometrium of uterus proliferates in

response to estrogen

Pathological Hyperplasia Abnormal proliferation of normal cells Tissues in organs as well as organs have

characteristic size For example, no 50 lb. kidneys Physiological mechanisms exist to

regulate size When mechanisms fail, proliferation

occurs

Abnormal Proliferation Hemangioma Proliferation of capillaries, results in

blood red birth mark Cells are relatively normal

Hemangioma Too much of a good thing. Lots of blood

close to the surface.

Atypical Hyperplasia Dysplasia is also used Cells are of abnormal size, shape and/or

organization Mature cells Not adaptation Common in cervix, respiratory tract

Dysplasia

Will These Cells Become Cancer??? Experts disagree Abnormal, but not cancer Different degrees of abnormality Can stage them Doesn’t necessarily mean progression

Metaplasia Meta means change (metamorphosis) Reversible change or replacement of

one normal tissue type with another normal tissue type

Classic example respiratory epithelium can change from ciliated pseudostratified columnar epithelium to stratified squamous epithelium

Metaplasia

Metaplasia in Esophagus

Metaplasia in Respiratory Tract Response to irritation, smoke Can come from cigarettes, cigars, or

industrial smoke Protective mechanism to protect against

irritant

Relationship Between Cellular Changes and Neoplasia

Picture of the Smoker Coughs and gurgles in the morning Ciliated epithelium hard at work moving

mucus up to the mouth all day and night Smoker, no elevator for mucus Most noticeable in the morning 2-3 weeks of not smoking, cough goes

away Epithelium reverts to classic respiratory

epithelium

Smoker and Metaplasia

Anaplasia Anaplasia-cells lose the morphological

characteristics of mature cells and their orientation with respect to each other and to endothelial cells

Actual dedifferentiation Feature of malignancy

Normal Versus Abnormal

Cellular Changes

Cellular Injury Result of cell’s inability to maintain

balance with environment Injurious agent induces adaptation

mechanisms Adaptation fails Cell can’t carry out biochemical

processes Cellular injury results

Hypoxic Injury Lack of oxygen and nutrients Oxidation reaction fail Energy production reduced or stops Important processes requiring energy

stop or are reduced Ion pumping, e.g. Osmotic gradient results, cell swell

Hypoxia Atherosclerosis in femoral artery Cells try to adapt: Atrophy Skin thins Leg hair disappears Cells swell (not edema)

Swollen Cells Chemical reaction occur as reactants

bump up against each other Cell swell, distance between reactants

increases, reactions slow down Cell function disturbed

Injurious Agents Chemicals that are toxins or poison Chemical that fits into a reaction

scheme of the cell and blocks reaction Thousands of enzymes that control

reactions Bring reactants together

Enzyme with Pocket

Anabolic Reactions Two reactants bind to enzyme, enzyme

changes shape Bond is formed Product formed

Catabolic Reactions Sucrose binds Enzyme changes shape Bond broken Fructose and glucose are formed

Enzyme Function

Cyanide as a Poison Blocks energy producing reactions

(binds to cytochrome c oxidase) Cell gone in seconds Shuts down mitochondria Instantaneous Cyanide hits acid of stomach, forms

cyanide gas

Infectious Agent Lots of bacteria live in harmony with us

and in us Problem: Some injurious Some cause direct destruction

Tetanus Fecal material of animal containing

tetanus bacteria contaminate object Object penetrates skin, contaminates

individual Bacteria grow and release toxin Toxin latches onto Acetylcholine

receptor Causes tetanic contraction Eventually locks up respiratory muscles

Consequences Carbon dioxide builds up Acidic conditions shut down cells

Excessive Defense Reaction Tuberculosis Bacteria invade, macrophages engulf,

bacteria replicate within endosomes Lymphocytes, macrophages, and

fibrocytes wall off creating granuloma Classified as an granulomatous

inflammatory disease Tissue destroyed, scars form

Overactive Defense Immune response to an injurious agent Allergies

Nutritional Imbalance Abnormal mix of amino acids Enzymes not normal or structure not

normal Interferes with function Cell biochemistry abnormal

Physical Agents Heat, cold Temperature extremes Very hot surface causes damage Coagulation of proteins (think of a hard-

boiled egg)

Hyperthermia Temperature increases Feel cold as set-point for temperature

regulation in hypothalamus is reset Shivering thermogenesis increases heat

production Look pale, blood vessels constrict Dry skin, no sweat Temp rises to set-point

Hyperthermia As temp increases, we feel unable to

think clearly Cells malfunction at 101 or 102 At 105, death ensues The obvious signs we observe are those

of the nervous system All other organs and tissues also

malfunction

Consequences First temperature increase rate of chemical

reactions Speed up molecules, probability of reaction

increases Problem, not all reactions (enzymes) respond

in the same way to a given change in temperature

One part increases more than another, imbalance

Enzymes have an optimal pH and temperature

Summary The mechanism of injury induces

responses which are aimed to allow adaptation

Failure to adapt results in death

Physical Agents Continued Atmospheric pressure Rapid extreme changes Explosion: Expansion, compresses air Wave of pressure travels out from site First wave of high pressure followed by

low pressure First a push in then a pull out

Example of Ear Damage The tympanic membrane responds to

wave effects, moves violently, tears Explosion can tear skin by same

movement Rest of the body is full of water-can’t

compress

Biggest Problem Airways and lungs full of air Rapidly expand then compress Tears tissue Bleeding occurs Respiratory system fills with blood and

can suffocate

Example of Pressure Damage Bats near wind turbines die Blades on windmills huge, calculated at

tip as moving at 100’s of miles/hr Cut through air causing compression

and expansion or an extreme pressure gradient

Bats have more delicate alveoli than other birds, severely effected by pressure

Mechanism of BendsDecompression Sickness Atmospheric pressure increases as we

descend in the ocean Squeezes gas into body fluids Ascend slowly, respiratory compensates

by removing gas as blood goes through respiratory system

Move up fast bubbles form in tissue, tears tissue

Additional Damage Bubbles in blood block small vessels

causing disturbance in blood flow CNS effect first, confusion, see colors Called nitrogen narcosis

Example Astronaut moves out of capsule Unpressurized area Must wear pressurized suit or will be

ripped to shreds

Hyperbaric Chamber Create high pressure Squeeze oxygen into tissues Can kill bacteria like tetanus or gas

gangrene Obligate anaerobes Lack superoxide dismutase Can’t survive oxygen-rich environment

Ionizing Radiation X-Ray hits molecule, electron bounces

off, creates “free radical” Highly reactive Reacts with another molecule Could bind to an enzyme, inactivate

enzyme Generally not a problem as is on small

scale

Free Radicals and DNA Free radical joins with DNA DNA contains information about enzyme

and other protein construction Instruction destroyed, cell dies Only one cell not a big problem

Serious Problem Free radical joins DNA in a way that

leads to uncontrolled division Locks on DNA causing tumor formation Excessive radiation: Nuclear accident-develop cancer

Which Tissues Effected by Radiation? Skin Bone marrow Epithelia Fetus Primarily male gonads All have rapid division

Mechanism Resting cell, DNA tightly coiled around

histone proteins Protected against free radicals Replication- uncoiled DNA, expose

nucleotides Free radicals join with part of DNA and

upset control mechanisms Uncontrolled proliferation, tumor

formation

Results of Cellular Injury Accumulations: Water: Cell injury Energy production

Pumping ion accumulation osmotic pressure swelling reaction rates change

Reactants far apart- imbalance in chemistry of cell

Hydropic Degeneration Irregular round inclusions Distended organelles: MTC, ER Called vacuoles Path report: hydropic degeneration Due to accumulation of water Reversible change

Lipid Accumulations Injurious agent causes abnormal

biochemistry Accumulate fat molecules Lipid in water illustrates the condition Lipid comes together and avoids water Obesity, diabetes and alcoholism most

common cause

Starvation Unable to burn fat Inadequate nutrition, lack of enzymes

due to inability to make protein Can mobilize fat from storage but sits in

liver due to inability to metabolize Liver enlarges

Genetic Diseases Inherited diseases of metabolism For example: glycogen, galactose,

tyrosine or homocysteine Inborn errors of urea cycle enzymes or

involving mitochondria in FFA oxidation

Toxic Compounds Alcoholism leads to fatty liver disease Carbon tetrachloride and other organic

solvents can lead to fatty liver Tetracycline, valproic acid, and

salicylate Corticosteroids Can cause microvesicular fatty liver

Calcium Accumulations Calcium accumulates in cell after injury Due to damaged calcium pump Calcium percipitates and forms crystals

in tissue

Dystrophic Calcification See in dead or dying tissues Severely damaged cells in

atherosclerosis Smooth muscle cells in arterial wall are

damaged and develop an atheroma which then calcifies

Blood vessel gets stiff and hard Epthelium degenerates, gets rough and

forms clots

Metastatic Calcification Occurs in many parts of the body Due to hypercalcemia ECF Ca++ concentration is close to

percipitation Change conditions, percipitation occurs Basic or alkaline percipitate For example in bone, normally

Calcification Change in blood vessel wall, percipitate Opposite is true: change conditions,

decalcification Example: Tumor in marrow cavity,

demineralization, bone can break Can be first sign of disease

Hyaline Change Accumulation of glassy translucent

crystals Denatured protein Can occur in abnormal condition:

Immune reaction, clumps of antigen-antibody complex

Indicates cell injury

Cell Death Necrosis is localized cell death while

majority of the animal is alive Visible change Heart attack-can see area of necrotic

tissue

Autolysis Self-digestion Lysosomes digest tissue Happens immediately, within seconds Study fixed tissue with light microscope,

all appears well Study und electron microscope see

damage Takes too long for fixative to prevent

damage

Immune Reactions Attack on dead cells Removed by macrophages Pathologist sees pyknotic nuclei Clumped nuclear material Karyolysis then occurs where

membranes degenrate Organelles disappear

Gross Necrosis What you can see with the naked eye Coagulative Proteins degenerateclumpmaintain

architecture of tissue Heart attack, part of heart wall dies Looks like heart wall Maybe different color, swollen, hard

Coagulative Necrosis

Gross Necrosis Occurs in specific tissues due tissue

type, cause of death, and environment conditions

Macrophages invade, inflammation develops

Replaced by scar tissue, gel and fibers

Liquefactive Necrosis Hydrolytic enzymes dissolve tissue Form pocket of liquid (cyst) Surrounded by healthy tissue or capsule Occurs in brain

Liquefactive Necrosis No connective tissue in brain Cut off blood supply, no connective

tissue to maintain structure Forms fluid-filled pocket Glial cells move in and form scar

Liquefactive Necrosis

Caseous Necrosis Cottage-cheese like Between the two-types Some coagulation, some liquefaction Lumps of tissue with liquid around them Often associated with infections caused

by myobacterium tuberculosis

Caseous Necrosis

Fat Necrosis Open up abdomen, white flaky stuff Dry white crystals Caused by leakage of pancreatic

enzymes Lipase breaks down fat FFA combine with sodium and form soap

Fat Necrosis in Pancreatitis

Summary Cells are injured Try to adapt May die These mechanisms are common to the

disease process