Transcript CELLULAR ADAPTATION

Cellular Adaptation: Pathophysiology
The cell is the fundamental unit of disease
Wanda Lovitz, MSN, APRN
Objectives: Cellular
Adaptation

Cite the general purpose of changes in cell structure and function that occur
as the result of normal adaptive processes.

Describe cell changes that occur with atrophy, hypertrophy, hyperplasia,
metaplasia, dysplasia, anaplasia, and neoplasia.

Cite three sources of intracellular accumulations.

Differentiate between the effects of ionizing and non-ionizing radiations.

State how biological, physical, and chemical agents injury cells.

Describe cell changes that occur with ischemia and hypoxic cell injury.

Cite the reasons for the changes that occur with wet, dry, and gas gangrene.
Cellular Adaptation
 Permits survival and maintenance of cell function
 May alter differentiation of genes enabling a cell to
change size or form.
 Is a normal adaptive response to an appropriate
stimulus
 Abnormal cellular changes may also occur
Atrophy
(cells shrink)
 D/t  workload or adverse
environmental conditions
 Is adaptive and reversible
 results in a decrease in cell size
 Types
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

Unilateral
Disuse atrophy (paralysis)
Degeneration atrophy (MS)
Ischemic atrophy (kidney, heart)
Malnutrition atrophy (starvation)
Loss of endocrine stimulation (uterine, breast)
Bilateral Atrophy
Brain atrophy
Research has shown
we are less likely to loose
brain function if we continue
to engage all parts of the brain
(Brain atrophy with Alzheimer's) - Atrophic cells have lost endoplasmic
reticulum, have fewer mitrochrondria, and myofliaments.
HYPERTROPHY
( size of cells)
 D/T  workload requirement of an organ part
 Causes an increase in cell size & cell function
 *See  protein in cellular components with no  in
cellular fluid
 Results in an increase in tissue mass

Seen in cardiac, skeletal, and muscle tissue
 These cells are not capable of mitosis (so, no  number or hyperplasia)
 May be a normal physiologic response
 as seen in an increase in muscle size with exercise
HYPERTROPHY
 May be a pathological response as in
myocardial hypertrophy from HTN or valve
disease
 Example: Left ventricular hypertrophy (LVH) –
 A PATHOLOGICAL HYPERTROPHY resulting in  size of
heart d/t  workload caused by HTN.
 There is an increase in size but function is compromised
 However, there is a LIMIT to the amount the tissue can
enlarge
•
Left Ventricular Hypertrophy
LVH) – seen with poorly
controlled HTN
•
Myocardial cells enlarge
d/t  workload of pumping
HYPERPLASIA
( # of cells)
 Occurs d/t to a response from appropriate
stimulus and ceases when stimulus is
removed
 An increase in NUMBER of cells
 Restricted to cells capable of mitosis
 epidermis, intestinal epithelium, and glandular
tissue.
 Physiological hyperplasia
 uterus and breast enlarge in pregnancy
HYPERPLASIA
(cont)
 May be a PHYSIOLOGICAL response and occur with
hypertrophy ( in both cell size & number)
 Hyperplasia is important in wound healing
 May also be a non-physiologic hyperplasia
 Seen in prostatic hypertrophy (BPH), endometrial hyperplasia
d/t increased hormone stimulation, or thyroid enlargement
Goiter – thyroid
hyperplasia
Benign Prostatic Hypertrophy/Hyperplasia
(BPH) – can cause difficulty
with urination
Hyperplasia seen in finger
warts: epidermal hyperplasia d/t viral
stimulation
Verrucae vulgaris – common warts
Plantar warts  in # of
epidermal
cells
( DNA synthesis and mitotic division)
METAPLASIA
 One cell type is replaced by another
 May predispose to cancer
 Involves reprogramming of undifferentiated stem
cells
 Allows to cells to better survive in a hostile
environment
 Is REVERSIBLE
 Is a response to chronic irritation and inflammation
METAPLASIA

Cells that are normally columnar or stratified may
change to squamous.

Examples:



With continued smoke exposure, ciliated columnar cells are
changed to stratified squamous cells
Cervical cells change when exposed to STDs or HPV
Think metamorphosis or change from one form to
another

Continued exposure may predispose to cancerous
transformations.
Ciliated columnar cells
Stratifiied squamous cells
DYSPLASIA*(ATYPICAL
HYPERPLASIA)
 Deranged cell growth resulting in cells of varying size, shape, and
appearance
 May be associated with chronic irritation or inflammation
 May be reversible if offending agent is removed
 Dysplasia is considered A STRONG PRECURSOR OF CANCER!!!
 Example: Cervical dysplasia
 However, dysplasia is an adaptive process
– may or may not
lead to cancer
 Decrease risk if irritation is removed or inflammation treated.
Anaplasia
 Cells differentiate to a more IMMATURE or embryonic
form.
 Malignant tumors are characterized by anaplastic cell
growth.
Ovarian cancer cells dividing
Summary: Cellular
Changes

Then anaplasia/neoplasia
CELLULAR ACCUMULATIONS
*(cellular infiltrations)
 Is a buildup of substances the cells are unable to
dispose of
 Is a result of cell injuries
 Examples
 Carbon/coal dust
 Lipids
 Fluid/edema
Cellular Infiltrations
carbon, triglycerides
 Carbon can accumulate via inhaled coal dust. Can cause
black lung disease (pneumonconiosis)
 Organs enlarged, i.e.,
“MEGALY”
 Ex. spleenomegaly, hepatomegaly
hepatomegaly
 Diseases d/t cellular accumulations MAY
BE REVERSIBLE
if d/t a correctable systemic disorder
 Example: elevated triglyceride levels can result in a “FATTY”
liver.
 This may reverse when triglyceride level is lowered with medication
CELLULAR ACCUMULATIONS:
lipids and edema
 If the offending cause is not or cannot be
corrected
 CELL DEATH may occur
 Example:
 Abnormal lipids in the brain of child with Tay-Sachs
disease (a genetic disorder) ultimately results in cell
death, and a shortened life span.
 cellular swelling – extracellular water shifts into cells
Cerebral edema
*Causes of cell injury
 Chemical agents
 Hypoxia
 Free radicals
 Infectious agents (bacteria, viruses, fungi)
 Physical and mechanical agents
 Genetic factors
 Nutritional imbalances
 **Individuals have different abilities to adapt to these stressors
What are Free Radicals?
Some free radicals
are formed during normal metabolism
Free radical – atoms or groups of
atoms with an odd (unpaired) number of electrons
Free radical theory of aging states that organisms age
because cells accumulate free radical damage over time
Antioxidants are believed to protect against free radical damage
CELLULAR INJURY
 Cause: Mechanical Forces
 Cellular injury may be reversible or irreversible
determined by: the severity of the insult, blood
supply, nutritional status, and regeneration
capability
 Physical Agents – trauma
 Electrical
 Temperature extremes
 Radiation
Mechanical Injury: Physical
Agents
Cause: Physical Agents
• Mechanical forces such as physical
trauma resulting in lacerations,
fractures, burns, injury to blood
vessels, and disruption in blood
flow.
laceration
Compound fracture
Mechanical force injury:
Electrical
 Can cause extensive tissue injury and disruption of
neural and cardiac impulses
 Vessels degenerate and create thrombi or clots
 The body acts as a conductor of electrical current. Can
see seizures or cardiac arrhythmias
 Extent of injury determined by the amount of voltage and
duration of exposure.
 Lightning and high voltage wires produce most severe
damage.
Mechanical force injury:
Temperature extremes
 Heat stroke or partial-thickness burns cause
cellular injury
 With an increase in intensity of heat, blood vessels
coagulate and tissue protein loss occurs Fried
egg effect
 Cold exposure increases blood viscosity and
induces vasoconstriction which may cause tissue
hypoxia
 Disrupts the cell membrane
Mechanical force injury:
Ultraviolet Radiation
 Sunburns increase the risk of skin cancers
 Damage to melanin-producing processes in skin
and damage to DNA occurs
 Risk of skin cancers  with number and
severity of sunburns
 Average 20 years from exposure to development
of skin cancer
Radiation injury:
Ionizing radiation
 Direct injury causes immediate cell death or deranged
replication
 The endothelial cells in blood vessels are very sensitive
Radiation dermatitis
stomatitis
Radiation Injury
 Ionizing radiation
 Chronic effect causes scarring or fibrosis
 Most radiation injury is d/t localized irradiation used to treat
cancer
 Effects DNA synthesis and interferes with mitosis
 Bone marrow and intestines are very vulnerable to
radiation exposure
Mechanical force:
Chemical Injury
 Cells may be damaged by a vast array of chemicals
 A biochemical interaction between a toxic substance
and the cell’s plasma membrane occurs and leads to 
cell permeability
 Examples
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air and water pollution
tobacco smoke
some processed or preserved foods
carbon monoxide
insecticides
trace metals such as lead, and DRUGS
Chemicals in tobacco
smoke
Tylenol/acetaminophen can cause chemical injury
to cells. The cells in which organ are most
affected by Tylenol?
A. Kidney
B. Brain
C.Liver
D.Heart
0%
A.
0%
B.
0%
C.
0%
D.
Chemical injury: Drugs
 May damage cells directly or indirectly
 Both prescription (RX) and over-the-counter (OTC)
medication can cause cell damage.
 Tylenol can damage liver cells
 Ibuprofen can injure kidney cells
 ETOH can harm gastric mucosa (gastritis) and liver
cells and harm the developing fetus
 Fetal Alcohol Syndrome
↔
Chemical injury: Drugs
 Anti-cancer drugs can directly injure normal
cells
 Some drugs produce metabolic end-products that
are toxic to the cells
 Example:
 Tylenol, which is detoxified in the liver, can cause
massive liver necrosis when taken in large
amounts
Lead paint tastes good.
A. True
B. False
0%
A.
0%
B.
Chemical injury:
Lead Toxicity
 Lead is absorbed via the GI
 Lead is very toxic to the
cells
 Sources include: flaking
paint, lead-contaminated
dust and soil, leadcontaminated root
vegetables, lead water
pipes, and newsprint
 Inhaled or ingested lead
accumulates over time
tract or via the lungs into the
blood
 Lead is toxic d/t multiple
biochemical effects:
 RBC’s become small and
pale (anemia)
 Since lead is excreted by
the kidneys, kidney
damage leading to renal
failure can occur
Lead
(cont)
 Lead causes demyelination of NERVE CELLS
in the cerebral and cerebellar matter
 causing death of neural and cortical cells
 Lead toxicity can cause
 a decrease in IQ
 impaired neurobehavioral development in children
 In adults see peripheral neuropathy
Injury from biological agents:
viruses, bacteria, and parasites
 Biological agents are able to replicate and thus can
continue to cause injury to cells
 Viruses incorporate themselves into the DNA of the cell
 Bacteria secrete exotoxins or endotoxins that interfere with
cellular reproduction of ATP, or release antitoxins that cause
injury
 Parasites can cause direct injury to the cell
bacteria
virus
salmonella
Injury from nutritional
imbalances
 Nutritional excesses such as obesity and diets high in
fats can predispose to atherosclerosis leading to
ischemia
 The body needs minerals, vitamins, certain fatty acids,
and specific amino acids.
 Nutritional and vitamin deficiencies interfere with cell
metabolism and delay wound healing

Infected decubitus ulcer
Hypoxic/Ischemia Cell Injury
*(the most common cell injury)
 Hypoxic injury
 Generalized
 Is an inadequate supply of O2 in BLOOD affecting the entire
body.
 Sx include change in LOC, confusion, combativeness
 Low pulse oximetry (less than 90%)
 Localized
 Causes ischemia of TISSUES
 If not corrected, can see infarction or death of tissues (heart, renal)
 Ischemia affects local tissue and is reversible
 Sx include pain, cyanosis,weak or absent pulses
 Infarction is tissue death and is not reversible.
Hypoxic injury
(cont)
 The cell reverts to anaerobic metabolism
causing a fall in PH
 lactic acid accumulates in the cell
lactic acidosis
 Causes of hypoxia
 Decrease of oxygen in the air
 Respiratory disease
 Ischemia
 Anemia d/t  hemoglobin
 Edema
Cellular Death
 Apopthosis
 Is essentially “cell suicide” or programmed cell
death
 Apopthosis is the process that eliminates:
 Worn out cells (RBCs)
 Cells which have been produced in excess
ex. WBCs with infectious response/hepatocytes with hepatitis)
 Cells which have developed improperly
ex. spontaneous abortion
 Cells which have genetic damage
Ex cancer
eschar
Necrosis
 Interferes with cell replacement and tissue
regeneration.
 Necrotic cells or tissue can:
 Liquefication
 cells becomes liquefied
 Ex: abcess, brain tissue
 May result in wet gangrene
 INFARCTION
 cells die and become BLACK AND SHRIVELED
A heart attack or myocardial infarction
results in irreversible cell damage.
A. True
B. False
0%
A.
0%
B.
The picture below is an
example of:
A. Wet gangrene
B. Dry gangrene
C.Gas gangrene
0%
A.
0%
B.
0%
C.
Gangrene

Gangrene is necrosis of a mass of tissue
 Death of many cells!

Results from severe hypoxia and subsequent
ischemia

Often seen with impaired circulation to lower
extremities (PVD, Diabetes)

Three types of gangrene:
1)
2)
3)
Dry gangrene
Wet gangrene
Gas gangrene
Dry Gangrene
 Part of the tissue becomes dry and shrinks, the
skin wrinkles and color changes to brown or
black




Shriveled/mummified
Spread is slow
Results from chronic ischemia of tissue
Symptoms not as marked as with wet gangrene
Dry Gangrene
 Line of inflammatory reaction occurs between dead
tissue and health tissue
 Usually d/t interference IN ARTERIAL supply to a part
without interfering with venous return so no swelling
 No bacterial infection
 Mostly confined to extremities
Note the clear line of demarcation
Moist or wet gangrene
 Frequently occurs in internal organs (appendix)
 If on the skin, surrounding area is cold, swollen,
and pulseless
 Skin in moist, black, and under tension
 Blebs form on the skin, liquefaction occurs, and foul
odor develops from bacteria
 No line of demarcation
 Spread is rapid
Moist or wet gangrene
 Severe systemic symptoms may develop
 Changes in VS, LOC, kidney function
 Death may occur
 Venous return is impaired so see swelling
 Bacterial invasion is present
 May affect extremities or internal organs
 Dry gangrene may become wet gangrene if a
bacterial invasion occurs
Gas Gangrene
*(destroys
connective tissue and cellular membranes)
 Is a specialized type of wet gangrene
 Results from infection of devitalized with clostridium
bacteria
 Anaerobic and spore forming, clostridium are often
found in the soil
 Gas gangrene is more prone to occur when there is
trauma with a compound fracture
Gas gangrene
Note characteristic gas bubbles
 Bacteria produce toxins which dissolve cell
membranes causing:
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
death of muscle cells
massive spreading edema
hemolysis of RBCs
renal toxicity
 Characteristic bubbles of hydrogen (sulfide
gas) form in the muscle
 Can be fatal