Transcript Introduction to Pathology

Introduction to Pathology
• Study of disease
• Disease:
– Defined as: an abnormal state in which part or all
of the body is not properly adjusted or is not
capable of maintaining homeostasis.
– The extent of a diseased condition and its effects
may vary from person to person; no two people
have the same disease in the same way.
– Some diseases will be more uniform in their
presentation, others will be variable
• Disease: depends on a number of factors, which we
will explore this term.
– It is important to recognize that diseases are not
things in and of themselves, but rather, they refer
to the condition of a person who is experiencing:
• A particular complex of causes
• Pre-conditions
• Physiological states
• Emotional states
• Mental states
• Genetic factors
• Exposure to infectious agents
• Exposure to environmental agents
• We need to stay focused on the individual who
is in a state of disease and not on a disease
entity which possesses a person.
• Injuries are abnormal states too. The major
difference between an injury and a disease is
that injuries refer to damage to tissues as the
result of excessive external physical or
chemical forces or violence.
Definitions Related to Pathology
• Etiology: study of the cause or theory of origin of a
disease.
– Idiopathic: In cases where the etiology is not known
(which is much of the time)
– Iatrogenic: In cases where the condition is caused by
a medical treatment.
– Iatros = doctor).
– For example, if someone develops liver
failure due to use of acetaminophen (a
common over the counter pain-killer).
• Pathogenesis: refers to the way in which the disease
develops
• Incidence: the range of occurrence of a disease.
Indicates a disease's tendency to occur among a
certain population, gender, age group, or geographic
location.
– Example, women are more prone to developing
auto-immune diseases.
– Sickle cell anemia has a higher incidence
in African Americans than in Native Americans
and people of European or Asian descent.
• Pathologic changes (pathophysiology):
– The changes in structure and function
characteristic of the disease.
• Signs and Symptoms: the manifestation of the
disease.
– Signs: are the objective facts; what the
practitioner can observe.
– Symptoms: are the subjective aspects; what the
patient feels.
• Syndrome: is a characteristic set of signs and
symptoms.
• Diagnosis: a statement about the, nature of the
disease. The doctor determines what the patient is
suffering from based on signs and symptoms and
diagnostic tests.
• Prognosis: a statement about the probable outcome
of the disease.
– In spite of the shortcomings of prognoses they give
a useful estimate of what is likely to happen and
how long it is likely to take so the therapist can
develop a treatment plan accordingly.
– Remember though that prognoses are educated
guesses; they are not definitive statements.
• Contraindications: statements about what kinds of
treatment are not appropriate for the condition.
• Complications: those things which may occur as a
result of the treatment that the practitioner should be
on the lookout for.
Related Definitions:
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Acute: Sudden rapid onset.
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Often denotes “severe” symptoms. Generally up to 48
hours.
Chronic: Of longer duration, slow progression,
shows little signs of change.
Communicable Disease: A disease that is spread
from person to person
Epidemic: appearance of an infectious disease
throughout a general area
Endemic: disease continuously occurring in a
particular population or area, usually of low mortality.
Pandemic: when an infectious disease is at epidemic
proportions in many places around the world.
– It has world-wide distribution. For example, there
is currently a pandemic of HIV/AIDS.
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Sporadic: occasional outbreak. A few occurrences of
the disease in different locations; nothing out of the
ordinary.
Congenital: present at birth
Acquired: not present at birth, develops later in life
Inherited: passed on through genetic makeup (Cystic
Fibrosis, Huntington’s Chorea)
Familial: “runs in the family,” but not directly
inherited (cancer, heart disease, hypertension etc.)
Mortality rate: The death rate for a specific region
or population affected by a specific disease
Morbidity: The ratio of those who are disease to
those who are well.
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Trauma: physical, chemical, or radioactive damage to
the body
Infection: invasion of a pathogenic microorganism
Degeneration: Breakdown of body tissues, usually
due to “wear and tear”
Autoimmunity: condition in which the body’s own
immune system destroy its own tissues
Virulence: the ability of an organism to cause a
disease; a measure of potency of a microorganism
Aerobe: An organism that lives in the presence of
oxygen
Anaerobe: An organism that can live without oxygen
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Asepsis: state of being without infection or
contamination; sterile
Antisepsis: inhibiting microorganism growth;
preventing reproduction
Disinfection: process used to KILL microorganisms
but not necessarily bacterial spores
Sterilization: process of completely removing all
living organisms, including bacterial spores
CELLULAR ADAPTATION,
INJURY/DEATH,
AND WOUND HEALING
Cellular Adaptation
When STRESSED cells undergoes adaptive changes
that permit survival and maintenance of function
It is only when the stress becomes so overwhelming in
conjunction with ineffective cellular adaptation that
cell injury and death occur
Typical cell adaptation processes include:
1. changes in size (Atrophy and Hypertrophy)
2. changes in cell number (Hyperplasia)
3. changes in cell type (Metaplasia)
4. changes in cell structure (Dysplasia)
• Mechanisms of cellular adaptation depend on signals
transmitted by chemical messengers that can alter gene
function in the cell.
• Generally two classes of genes in the cell:
• “Housekeeping” genes
– Necessary for normal function of the cell
• Differentiating characteristic genes
– Genes which determine differentiating characteristics
of a cell
– When under stress the expression of the differentiating
gene is altered, whereas the housekeeping genes
maintain normal expression
– Once stress is removed gene expression returns to
normal
Atrophy
• Def: The ability of cells to revert to a smaller size when confronted
with decreased work demands or adverse environmental conditions
• Purpose of atrophy is allow the cell to function at an efficient level
that is compatible with survival
• Rate of atrophy is directly related to the workload of a cell
• Cellular atrophy results in a decrease in the size and number of
organelles
• Causes of atrophy include:
– Disuse
- Loss of endocrine stimulation
– Denervation
- Decrease in blood flow
– Inadequate nutrition
Hypertrophy
• Hypertrophy: represents an increase in cell size which results
in an increase in the amount of functioning tissue mass
– Results from increased workload imposed on an organ or
body part
• At the cellular level, hypertrophy involves an increase in the
functional components of the cell.
• Normal muscle hypertrophy: occurs as a result of exercise
• Pathologic hypertrophy occurs as a result of adaptation or
compensation:
– Thicken urinary bladder: from long-term outflow
obstruction
– Myocardial hypertrophy from hypertension
Hyperplasia
Def: An increase in the number of cells in an organ or tissue
• Occurs in tissues with cells that are capable of mitotic division
such as:
– epidermis of the skin
– intestinal epithelium
– glandular tissue
Hyperplasia
• Two Types:
– Physiologic induction
• Two types
– 1. Hormonal: example of breast and uterine
enlargement during pregnancy
– 2. Compensatory: removal of one kidney results in
an increase in the other kidney
– Nonphysiologic induction: due to excessive hormonal
stimulation or the effects of growth factors on target
tissues. Example of excessive estrogen production causing
endometrial hyperplasia and abnormal menstrual bleeding.
Metaplasia
Def: Represents a reversible change in which one adult cell type
is replaced by another adult cell type
– The conversion of cells never oversteps the boundaries of
the
primary groups of tissues (epithelial tissue
will only convert to other
types of epithelium)
• Usually occurs in response to chronic irritation and
inflammation
• New cells are better able to survive, whereas, the more fragile
cell previously there would die
• Cell types are normal. For example simple cuboidal
epithelium changing to stratified squamous epithelium in
response to smoking
Metaplasia of laryngeal respiratory epithelium has occurred here in a smoker. The
chronic irritation has led to an exchanging of one type of epithelium (the normal
respiratory epithelium at the right) for another (the more resilient squamous
epithelium at the left). Metaplasia is not a normal physiologic process and may be
the first step toward neoplasia.
Dysplasia
Def: is characterized by abnormal cell growth of a specific tissue
that results in cells that vary in shape, size and appearance
• is strongly implicated as a precursor of cancer
• Frequently seen in areas of metaplastic squamous epithelium
of the respiratory tract and uterine cervix.
• Usually reversible once irritating cause is removed.
Intracellular Accumulations
• Intracellular accumulations are the buildup of substances that cells cannot use
or immediately dispose of.
• Accumulations can be:
– Normal body substances
• Occurs when a substance is produced at a rate exceeding metabolism
or removal.
• Example is fatty changes in the liver due to accumulation intracellular
triglycerides secondary to alcoholism
– Abnormal endogenous products
• Can occur from genetic disorders where a normal enzyme may be
replaced with an abnormal one.
• As a result substances are formed that the cell cannot use or eliminate
• Example is Von Gierke’s disease in which there is an accumulation of
glycogen in the cells due to a deficiency of glucose-6-phosphate.
– Exogenous products
• Include pigments which accumulate in the cell
• Example is jaundice caused by the retention of bilirubin.
Pathologic Calcifications
Def: The abnormal deposition of calcium salts, together with
small amounts of iron, magnesium, and other minerals.
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Two types of calcification:
1. Dystrophic calcification:
• The deposition of calcium in injured tissue
• Often visible to the naked eye
• Deposits range from gritty sand like grains to firm,
hard rock material
• Results from the crystallization of calcium
phosphate which is derived from dead or dying
cells, the circulation, and interstitial fluid
• Commonly seen in atheromatous lesions, the aorta,
large blood vessels, and damaged heart valves
2. Metastatic calcification
– Occurs in normal tissue as the result of increased
serum calcium levels (from any condition
increasing blood calcium levels)
– Common causes
» Hyperparathyroidism
» Renal failure
» Increase mobilization of calcium from bone
(Paget’s disease, metastatic carcinoma)
» Vitamin D intoxication
– Commonly occurs in the lung, renal tubules, and
blood vessels.
Cell Injury and Death
Causes of cell injury include:
1. Physical Agents
2. Radiation
3. Chemical
4. Biologic Agents
5. Nutritional Imbalances
Injury From Physical Agents
1.
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3.
Mechanical Forces: injury due to mechanical forces
occurs as the result of body impact with another object.
• Examples include bone fractures, soft tissue injuries,
bruises
Extremes of Temperature: extremes of heat and cold can cause
damage to the cell, cellular organelles, and enzymes.
• extreme heat may cause: inactivation of enzymes,
disruption of cell membrane, and coagulation of
blood vessels
• extreme cold may cause: severe vasoconstriction or ice
crystal formation
Electrical Injuries: can affect the body through extensive tissue
injury and disruption of nervous impulses
• the body acts as a conductor of the electrical current from
its source to the ground
• tissue damage results from heat production produced by
electrical current
Radiation Injury
1.
2.
3.
Ionizing Radiation- affects cells by causing the ionization of molecules and
atoms in the cell. Commonly caused by localized irradiation used in the
treatment of cancer
• Effects on cell include:
a. cell death
b. interruption of cell replication
c. development of genetic mutations
Ultraviolet Radiation (sunlight)- mainly causes sunburn and increased risk of
skin cancers
a. skin damage induced by UV radiation is caused by the
accumulation of free radicals that damage the melaninproducing processes in the skin
b. Xeroderma pigmentosum- a genetic disorder due to the lack
of an enzyme needed to repair the sunlight-induced damage to
DNA in skin cells, results in extreme photosensitivity
Nonionizing Radiation- includes infrared light, ultrasound, microwaves and
laser energy
a. causes tissue damage by inducing the vibration and rotation of
atoms and molecules within cells
b. the molecular vibrational and rotational energy is eventually
converted to thermal energy
Chemical Injury
Chemical agents can cause cellular damage by:
1. destruction of cell membrane
2. inhibiting normal function of enzymes
3. denaturation of cell proteins
4. disruption of the osmotic and ionic balance of the cell
Drugs: including alcohol, prescription drugs, OTC drugs, and street drugs can
directly or indirectly damage tissues. Many drugs are metabolized by the body
into chemicals that are toxic to cells
Lead Toxicity- lead is a very toxic metal that is absorbed through the lungs or
GI tract into the bloodstream
1. lead has the ability to:
a. inactivate key cellular enzymes
b. compete with calcium for incorporation into bone
c. interfere with nerve transmission
d. inhibit brain development
2. the major targets of lead toxicity are: red blood cells, cells of the GI
tract, kidneys, and nervous system
Biologic Agents and Nutritional
Deficiencies
• Biologic agents include viruses, bacteria, and parasites which
invade the cell
• Viruses cause cellular damage by incorporating itself into the
cellular DNA, resulting in the production of viral proteins
• Bacteria may injure cells by producing either exotoxins or
endotoxins.
• Nutritional excesses or deficiencies may also cause cellular
injury.
• Diets high in saturated fats predispose persons to atherosclerosis.
In contrast diets deficient in nutrients predispose persons to
numerous diseases (iron deficiency anemia, scurvy)
Mechanisms of Cell Injury
1. Free Radical Injury:
a. Free radical- is a highly reactive molecule arising from an atom
that has a single unpaired electron in its chemical outer orbit
causing the free radical to be unstable and enter into reactions
with key cellular molecules
b. Free radicals are produced by many normal cellular reactions in the
body. Including from the breakdown of lipids and proteins, and from the
inflammatory process
c. Unfortunately, molecular oxygen (O2), with its 2 unpaired outer
electrons is the most frequent source of free radicals
d. free radical-induced cellular damage may include:
1. damage to cell membranes
2. destruction of key cellular proteins
3. inactivation of enzymes
4. genetic mutation
e. most cells, under normal conditions have chemical mechanisms
that protect them from the free radical damage
Mechanisms of Cell Injury
2. Hypoxic Cell Injury:
a. Hypoxia- condition in which a cell is deprived of oxygen resulting in
the interruption of normal metabolic processes, most importantly ATP
synthesis
b. common causes of hypoxia include:
1. Inadequate concentration of oxygen in the environment
2. Respiratory disease
3. Ischemia- decreased blood flow
4. Anemia
c. Hypoxia causes a power failure in the cell, affecting the cell’s
functional and structural components
1. As oxygen levels fall, aerobic respiration, resulting in the
cells changing to anaerobic methods and the accumulation
of lactic acid in the cell (decreasing the pH) which damages
organelles within the cell.
2. As ATP levels decrease membrane Na+/K+ pumps begin to
fail resulting in increased levels of Na+ within the cell. As a
result water enters the cell via osmosis and causes cellular
swelling.
3. In addition, the endoplasmic reticulum and cell membranes
become more permeable.
4. If oxygen levels continue to decrease the lysosomal
membranes also become hyperpermeable resulting in the
release of enzymes into the cytoplasm and the digestion of
cellular components.
5. Leakage of cellular enzymes into the extracellular fluid is
used as an important clinical indicator of cell injury and
death.
Impaired Calcium Homeostasis
• Calcium functions as an messenger in the release of many
intracellular enzymes.
• Normally intracellular calcium levels are low in comparison to
extracellular levels. This gradient is kept via calcium/magnesium
pumps.
• Ischemia and certain toxins lead to an increase in cytosolic calcium
because of increased influx across the cell membrane and the release
of calcium from the ER and mitochondria.
• The calcium in the cytoplasm activates a number of enzymes which
can damage the cell. Activated enzymes include phospholipidases,
proteases, ATPases, and endonucleases.
Cell Death
Apoptosis- involves controlled cell destruction and is involved in the normal
process of cell deletion and renewal
a.
main goal is to eliminate worn out cells, cells produced in excess,
improperly developed cells, or genetically damaged cells.
b.
Apoptosis is characterized by controlled autodigestion of cell
components.
c.
cells appear to initiate their own death through the activation of
endogenous enzymes
d.
This results in cell shrinkage, condensation of organelles, disruption and
clumping of nuclear DNA, and wrinkling of the cell membrane.
e.
Normally apoptosis occurs during the involution of endometrial cells
during the menstrual cycle and the regression of breast tissue following
the cessation of breast feeding
f.
Apoptosis is thought to be involved in cell death with certain viral
infections, cell death with a variety of injurious agents (mild thermal and
radiation injury)
Necrosis- is a pathologic form of cell death in an organ or tissue that is part of
a living person.
a. Differs from apoptosis in that it involves unregulated enzymatic
digestion of cell components, loss of cell membrane integrity, and
the initiation of the inflammatory response.
b. Necrosis interferes with cell replacement and tissue regeneration.
c. Types of necrosis;
1. Liquefaction necrosis: occurs when cells die, but their
catalytic enzymes are not destroyed. Example is seen in
the softening in the center of an abscess.
2. Coagulative necrosis: Seen in infarcted areas in hypoxic
cellular injury resulting in acidosis and denaturation of
enzymes and structural proteins of the cell.
3. Caseous necrosis: Form of cell death where dead cells
persist indefinitely as soft cheeselike debris. Commonly
seen in the tubercle granulomas of tuberculosis.
Gangrene
Gangrene is the term applied when a considerable mass of tissue
undergoes necrosis.
Three types
1.
Dry gangrene:
a. Results from interference with arterial blood supply without
the interference of venous return and is a form of
coagulative necrosis.
b. Tissue becomes dry and shrinks, skin wrinkles, and color
changes to dark brown or black.
c. There is a line of demarcation between dead tissue and
healthy tissue
d. Spread of dry gangrene is slow
e. Usually confined to the extremities
2. Moist (Wet) gangrene:
a. Results from interference of venous return from the
body part.
b. Area is cold, swollen, pulseless. Skin is moist, black,
and under tension.
c. Blebs form on the surface, liquefaction occurs and
there is a foul odor due to bacterial action.
d. There is no line of demarcation.
e. Spread of tissue damage is rapid.
f. Death may occur unless the condition is controlled.
g. Can occur in the extremities and/or the internal organs
h. If bacteria invade the necrotic tissue, dry gangrene
can be converted to wet gangrene.
3. Gas Gangrene:
a. Type of gangrene resulting from infection of tissues from
one of several anaerobic Clostridium bacteria,
commonly Clostridium perfringens
b. Gas gangrene tends to occur in wounds where dirt and
debris are embedded as Clostridium is found in the soil.
c. The bacteria produce enzymes that dissolve cell
membranes, causing death of muscle cells, massive
spreading edema, hemolysis of RBC’s, hemolytic
anemia, hemoglobinurea, and renal failure.
d. Characteristics include bubbles of hydrogen sulfide gas
that form in the muscle.
e. Potentially fatal, possibly requiring amputation
Connective Tissue Repair
Wound healing is divided into three phases:
1. Inflammatory Phase:
a. begins at the time of injury is described as the stage that
prepares the wound environment for healing
b. there is vasoconstriction of any injured blood vessels and
the initiation of the blood clotting mechanism in order to
prevent excessive bleeding
c. once any bleeding has been controlled, the blood vessels of
the wound environment vasodilate allowing plasma and blood
components to enter the injured area
d. migration of WBCs to area initiates the digestion and
removal of any foreign organisms and tissue debris and to
stimulate the re-growth of tissue components
2. Proliferative Phase:
a. usually begins within 2-3 days of injury and may last as
long as 3 weeks
b. the processes of this stage focus on the building of new
tissue to fill the wound space
c. the cellular workhorse of this stage is the fibroblast- cell
that synthesizes and secretes collagen
d. physical manifestation of this stage is scab formation
3. Remodeling Phase:
a. begins approximately 3 weeks after the initial injury and
can continue for 6 months or longer
b. this stage is marked by continued remodeling of scar tissue
by the simultaneous synthesis of collagen by fibroblasts and
the breakdown of collagen by enzymes in order to increase the
tensile strength of the wound area