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Pathophysiology Exam - Exam 1, Cell Transport

Foundations O Pathophysilogy (Nova Southeastern University)

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Pathophysiology Exam #1

Cellular Adaptation, Injury, and Death

Cellular adaptation is when cells adapt to changes in the internal environment when
confronted with stresses that endanger normal structure and function. Cells adapt to
increased work demands by changing in:

 Size (atrophy and hypertrophy)

 Number (hyperplasia) – number of cells
 Form (metaplasia) – how they look

A cell is able to change its size or form without compromising its normal function.

Atrophy is a decrease in cell size when confronted with decrease in work demands and
adverse environmental conditions. Atrophy is adaptive and reversible (Ie. Muscle size is
restored after the cast is removed and muscle use is resumed). Causes of atrophy:

 Disuse (stop using it – arm or foot in a cast)

 Denervation – Occurs in the muscles of paralyzed limbs
 Loss of endocrine function
 Inadequate nutrition
 Ischemia or decreased blood flow

Hypertrophy refers to an increase in cell size and functioning tissue mass. This leads to
an increased workload (cardiac/skeletal muscle) and disease conditions. Normal
physiologic hypertrophy is exercise. Then you have pathologic hypertrophy that occurs as
the result of disease conditions and may be adaptive or compensatory:

 Adaptive hypertrophy are the thickening of the urinary bladder rom long-
continued obstruction of urinary outflow and myocardial hypertrophy that results
from valvular heart disease or hypertension
 Compensatory hypertrophy is the enlargement of a remaining organ or tissue after
a position has been surgically removed or rendered inactive. For example, if one
of the kidneys is removed, the remaining kidney enlarges to compensate for the
loss.

Hyperplasia refers to an increase in the number of cells in an organ or tissue. This occurs
in tissues with cells that are capable of mitotic division, such as epidermis, intestinal
epithelium, and glandular tissue. Certain cells (neurons) rarely divide and have little
capacity, if any, for hyperplastic growth. Evidence shows that hyperplasia involves
activation of genes, which cause replication. Hyperplasia can either be physiologic or
non-physiologic:

 Physiologic hyperplasia refers to hormonal and compensatory.

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o Hormonal physiologic hyperplasia - Breast and uterine enlargements

during pregnancy are examples of a physiologic hyperplasia that results
rom estrogen stimulation.
o Compensatory physiologic hyperplasia – The regeneration of the liver
that occurs after partial hepatectomy (partial removal of liver)

 Non-physiologic hyperplasia usually is due to excessive hormonal stimulation or

the effects of growth factors on target tissues. The laboratory term hyperplasia
should be taken seriously. For example endometrial hyperplasia is due to
excessive estrogen production and is considered a high risk or developing
endometrial cancer. Benign prostatic hyperplasia is related to the action of
androgens and causes lower urinary tract symptoms and sometimes develops into
prostate cancer. Atypical hyperplasia of the breast is monitored carefully since
they have a fourfold higher risk of developing invasive breast cancer (ductal
carcinoma).

Metaplasia refers to a reversible change in which one adult cell another adult replaces
type cell type. For example, an adaptive substitution of stratified squamous epithelia cells
for the ciliated columnar epithelial cells. Metaplasia usually occurs in response to chronic
irritation and inflammation (someone who smokes or the development of Barrett
esophagus in those people with chronic gastro-esophageal reflux disease [GERD]).

Dysplasia refers to deranged cell grown with cells varying in size, shape, and
organization. Minor degrees of dysplasia are associated with chronic irritation or
inflammation. Dysplasia is abnormal but is potentially reversible if the known cause has
been removed. Dysplasia is strongly implicated as a precursor of cancer.

Intracellular accumulations refer to the buildup of substances, which the cell can’t
eliminate or use immediately. This accumulation occurs when a substance is produced at
a rate that exceeds its metabolism or removal. These substances can be grouped into three
categories:

 Normal body substances (lipids, proteins, carbohydrates, melanin, and bilirubin)

 Abnormal endogenous products – Resulting from inborn errors of metabolism.
Often the disorder cannot be corrected causing cell injury and death.
 Exogenous products (environmental agents and pigments, that cannot be broken
down by the cell)

An example would be fatty changes in the liver due to intracellular accumulation of

triglycerides. In von Gierke disease, large amounts of glycogen accumulate in the liver
and kidneys because of a deficiency of the enzyme glucose-6-phosphatase and without
this enzyme, glycogen cannot be broken down therefore leading to the accumulation of
glycogen and a reduction in blood glucose levels. In Tay-Sachs disease, abnormal lipids
accumulate in the brain and other tissues, causing motor and mental deterioration
beginning at 6 months of age, followed by death at 2-5 years of age. Jaundice is an
example of an endogenous feature due to increase bilirubin from red blood cell

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destruction, obstruction of bile passage into the intestine, or toxic disease that affect the
liver’s ability to remove bilirubin from the blood. An exogenous product would be carbon
in the form of coal dust in a coal mine. This blackens the lung tissue and causes serious
lung disease.

Pathologic calcifications involve abnormal tissue deposition of calcium salts, together

with smaller amounts of iron, magnesium, and other minerals. It is either known as
dystrophic calcification when it occurs in dead or dying tissue or metastatic calcification
when it occurs in normal tissue.

 Dystrophic calcification refers to the macroscopic deposition of calcium salts in

injured tissue. It is often visible to the naked eye as deposits that range from
gritty, sand like grains to firm, hard rock material. Ie. Aortic stenosis, large
deposits of calcium salts in the aorta
 Metastatic calcification occurs in normal tissues as the result of hypercalcemia
(increased serum calcium levels). This leads to inappropriate calcification in the
lungs, renal tubules, and blood vessels. Primary causes are hyperparathyroidism,
either primary or secondary to phosphate retention in renal failure, increased
mobilization of calcium from bone as in Paget disease, cancer with metastatic
bone lesions, or immobilization and in vitamin D intoxication.

Cell Injury

Cells can be damaged in a number of ways, including physical trauma, extremes of

temperature, electrical injury, exposure to damaging chemicals, radiation damage, injury
from biologic agents, and nutritional factors.

Most injurious agents exert their damaging effects through uncontrolled free radical
production, impaired oxygen delivery or utilization, or the destructive effects of
uncontrolled intracellular calcium release.

Injury from physical agents include:

 Mechanical forces – Injury or trauma occurring as the result of body impact with
another object. These types of injuries split and tear tissue, fracture bones, injure
blood vessels, and disrupt blood flow.
 Extremes of temperature – Extremes of heat and cold damage the cell.
o Low-intensity heat (43 C to 46 C), which include partial-thickness burns
and severe heat stroke, causes cell injury by inducing vascular injury,
accelerating cell metabolism, inactivating temperature-sensitive enzymes,
and disrupting the cell membrane.
o Intense heat leads to coagulation of blood vessels and tissue proteins
occur.
o Exposure to cold increases blood viscosity and induces vasoconstriction,
which leads to decreased blood flow and therefore possible hypoxic tissue
injury.

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 Electrical injuries affect the body through extensive tissue injury and disruption
of neural and cardiac impulses. Electricity may interrupt impulses from the
respiratory centers in the brain stem, and through the chest causing fatal cardiac
arrhythmias.

Radiation injury:

 Ionizing radiation causes ionization of molecules and atoms in the cell. Most
radiation injury is caused by localized irradiation that is used in the treatment of
cancer. Over time, this can lead to increased chances of developing skin cancers,
leukemia, osteogenic sarcomas, and lung cancer. This is especially true when the
person is exposed to radiation during childhood.
 Ultraviolet radiation causes sunburn and increases the risk of skin cancers.
 Nonionizing radiation includes infrared light, ultrasound, microwaves, and laser
energy.

Chemical injury are when chemical agents injure the cell membrane and other cell
structures, block enzymatic pathways, coagulate cell proteins, and disrupt the osmotic
and ionic balance of the cell.

 Drugs include alcohol, prescription drugs, over-the-counter drugs, and street

drugs are capable of directly or indirectly damaging tissues. For example, ethyl
alcohol can harm the gastric mucosa, liver, developing fetus, and other organs.
Acetaminophen (Tylenol) detoxifies in the liver and therefore too much of it can
damage the liver.
 Carbon tetrachloride is a chemical that causes little damage until it metabolized
by liver enzymes in which it is extremely toxic to liver cells.
 Lead toxicity – The major targets of lead toxicity are red blood cells, the
gastrointestinal tract, the kidneys, and the nervous system. Anemia is common as
lead competes with the enzymes required for hemoglobin synthesis and with
membrane-associated enzymes that prevent hemolysis of red blood cells. The
kidneys are the major route for excretion of lead and lead can cause kidney
damage and also lead to hypertension. In the nervous, lead toxicity is
characterized by demyelination of cerebral and cerebellar white matter and death
of cortical cells. When this occurs in early childhood, it can affect development
and IQ levels. The most serious manifestation of lead poisoning is acute
encephalopathy, which is characterized by persistent vomiting, ataxia, seizures,
papilledema, impaired consciousness, and coma. EP (erythropcye protoporphyrin)
is a test when they take blood from a finger stick to check for lead levels;
however, it does not display lead levels below 20-25. For better results, obtain a
venous blood sample.
 Mercury toxicity – Mercury (eating fish) should be avoided in young children,
pregnant, and nursing women because the developing brain is more susceptible to
the effects of mercury.

Biologic Agents Injury Viruses, parasites, bacteria

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Injury from Nutritional Imbalances refers to nutritional excesses and nutritional

deficiencies and how they predispose cells to injury. For example, obesity and diets high
in fat predispose persons to atherosclerosis. Low protein can cause tissue damage while
low iron consumption can lead to iron-deficiency anemia.

Mechanisms of Cell Injury is when injurious agents cause cell injury and death. Some
agents, such as heat, produce direct cell injury. Other factors, such as genetic
derangements, produce their effects indirectly through metabolic disturbances and altered
immune responses.

 Free radicals are highly reactive chemical species with an unpaired electron in
the outer orbit of the molecule. This occurs normally in the body with the
breakdown of metabolic wastes but exogenous causes, including ionizing and UV
radiation, can cause reactive oxygen species (ROS) (which have free radicals)
production in the body. When the body is unable to neutralize and eliminate
ROS, this leads to oxidative stress, which in turn can lead to oxidation of cell
components, activation of signal transduction pathways, and changes in gene and
protein expression. GNA modification and damage can occur as a result of
oxidative stress. Oxidative damage has been implicated in many diseases
including:
o Mutations in the gene for SOD, which is linked with amyotrophic lateral
sclerosis (ALS; Lou Gehrig disease)
o Development of cancer
o Reestablishment of blood flow after loss of perfusion is associated with
oxidative injury to vital organs
o The endothelial dysfunction that contributes to cardiovascular disease
Antioxidants inhibit reactions of ROS and free radicals. They include Vitamin A,
E, C, glutathione, flavonoids, selenium, and zinc.

 Hypoxic Cell Injury is when hypoxia deprives the cell of oxygen and interrupts
oxidative metabolism and the generatio of ATP.

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