Adaptasi dan kelainan sel

Agni Laili Perdani, MS

Department of Pediatric Nursing
Sekolah Tinggi Ilmu Keperawatan (STIKep) PPNI JAWA BARAT
Case Study
• The player is a 26-yo male professional soccer player who is internationally
capped and currently competing in the English Premier League.
• The player’s physical characteristics : body mass, 77 kg; height 179 cm. The
player had been a full-time professional player since age 18 and had therefore
been engaged in daily structured soccer-specific training for 5+ years.
• At the time of injury, the athlete was engaged in daily field-based soccer-specific
training, 3 resistance-training sessions per week (1 focusing on lower limbs and 2
focusing on upper limbs) and 1-2 competitive games per week.
• The player presented with a total rupture of the ACL ligament in his left knee.
Surgery was performed 6 days after injury occurrence and involved surgical
ligament reconstruction using a graft from the ipsilateral patella tendon to
replace the damaged ACL.
• Whole body and regional rates of muscle atrophy and hypertrophy (as inferred
by assessments of fat free mass from DXA)
Outline :
1. Athropy
2. Hypertrophy& hyperplasia
3. Degenerasi & infiltrasi
4. Metaplasia
5. Dysplasia
6. Anaplasia
7. Necrosis
OVERVIEW (1/2)
• Cells are active participants in their environment, constantly adjusting
their structure and function to accommodate changing demands and
extracellular stresses.
• Cells tend to maintain their intracellular milieu within a fairly narrow
range of physiologic parameters (normal homeostasis)
• As cells encounter physiologic stresses or pathologic stimuli, they can
undergo adaptation, achieving a new steady state and preserving
viability and function.
• The principal adaptive responses are hypertrophy, hyperplasia,
atrophy, and metaplasia. If the adaptive capability is exceeded or if the
external stress is inherently harmful, cell injury develops
OVERVIEW (2/2)
• Within certain limits injury is reversible and cells return to a stable
baseline
• Severe or persistent stress results in irreversible injury and death of
the affected cells.
• Cell death is one of the most crucial events in the evolution of disease
in any tissue or organ.
• It results from diverse causes, including ischemia (lack of blood
flow), infections, toxins, and immune reactions.
• Cell death is also a normal and essential process in embryogenesis,
the development of organs, and the maintenance of homeostasis.
Athropy
• Atrophy is defined as a decrease in the size of a tissue or
organ due to cellular shrinkage caused by the loss of
organelles, cytoplasm and proteins
• Atrophy can be caused by genetic, environmental, lifestyle,
or disease-related factors, decreased nutrient supply or
disuse; associated with decreased synthesis and increased
proteolytic breakdown of cellular organelles
Causes of atrophy (1/2)
1. A decreased workload (e.g : immobilization of a limb to
permit healing of a fracture)
2. Loss of innervation
3. Diminished blood supply
4. Inadequate nutrition
5. Loss of endocrine stimulation
6. Aging (senile atrophy)
Causes of atrophy(2/2)
• Atrophy results from decreased protein synthesis and increased
protein degradation in cells.
• Protein synthesis decreases because of reduced metabolic activity.
The degradation of cellular proteins occurs mainly by the ubiquitin-
proteasome pathway.
• Nutrient deficiency and disuse may activate ubiquitin ligases, which
attach multiple copies of the small peptide ubiquitin to cellular
proteins and target these proteins for degradation in proteasomes.
• Atrophy is also accompanied by increased autophagy, with resulting
increases in the number of autophagic vacuoles. Autophagy ("self-
eating") is the process in which the starved cell eats its own
components in an attempt to find nutrients and survive.
A. Normal brain of a young adult.
B. Atrophy of the brain in an 82-year-old male with atherosclerotic disease. Atrophy of the
brain is due to aging and reduced blood supply. Note that loss of brain substance narrows the
gyri and widens the sulci. The meninges have been stripped from the right half of each
specimen to reveal the surface of the brain.
 Type of Athropy
1. Skeletal muscle
2. Spinal muscle
3. Multiple system
Muscle atrophy : the wasting or loss of muscle tissue
Physiologic
Had seated jobs, health
problems limit movement,
or decreased activity levels
Are bedridden
Cannot move their limbs
because of stroke/ other
brain disease
Are in a place that lacks
gravity, such as during
space flights
Pathologic Neurogenic
aging Amyotrophic lateral sclerosis
(ALS, or Lou Gehrig disease)
Starvation Damage to a single nerve (carpal
tunnel syndrome)
Cushing Gullian-Barre syndrome
syndrome
Nerve damage caused by injury,
diabetes, toxins, or alcohol
Polio (poliomyelitis)
Spinal cord injury
Spinal Muscular Atrophy (SMA)

• Definition : Genetic condition caused by the loss of

nerve cells that control muscle movement
throughout the body.
• Chromosome 5 SMA is caused by a deficiency of a
motor neuron protein called SMN “survival of motor
neuron” for normal motor neuron
• The primary symptom of chromosome 5-related
(SMN-related) is weakness of the voluntary muscles.
• The muscles most affected are those closest to the
center of the body (the shoulders, hips, thighs and
upper back). Special complications if the muscles used
for breathing and swallowing are affected, resulting in
abnormalities in these functions
Multiple System Atrophy (MSA)
• Definition : Progressive neurodegenerative disorder characterized by a
combination of symptoms that affect both the autonomic nervous system (the
part of the nervous system that controls involuntary action such as blood
pressure or digestion) and motor impairment.
• The symptoms reflect the progressive loss of function and death of different
types of nerve cells in the brain and spinal cord.
• Clinical manifestation :
1. Rigid muscles with trouble bending arms and legs, slow movements,
Shakiness, problems with balance, Slurred, quiet, or slow speech, blurry vision
2. Trouble chewing or swallowing, severe blood pressure changes when sitting
and standing
3. Urinary changes, Sleep changes
4. Abnormal sweating, Sexual dysfunction
5. Cardiac issues
6. Psychiatric issues
Types of MSA
1. The Parkinsonian type (MSA-P) : primary characteristics similar to
Parkinson’s disease (moving slowly, stiffness, and tremor) along
with problems of balance, coordination, and autonomic nervous
system dysfunction
2. The Cerebellar type (MSA-C): Primary symptoms featuring ataxia
(problems with balance and coordination), difficulty swallowing,
speech abnormalities or a quavering voice, and abnormal eye
movements (“cerebellar” reflects a part of the brain involved with
coordination)
Hypertrophy (1/2)

• Hypertrophy: Enlargement or
overgrowth of an organ or part of
the body due to the increased
size of the constituent cells
• Often in response to increased
workload; induced by mechanical
stress and by growth factors;
occurs in tissues incapable of cell
division
 Hypertrophy (2/2)
• Hypertrophy : No new cells, just bigger cells, enlarged by an increased amount
of structural proteins and organelles.
• Hypertrophy can be physiologic or pathologic caused either by increased
functional demand or by specific hormonal stimulation.
• Hypertrophy and hyperplasia can also occur together in an enlarged
(hypertrophic) organ (The massive physiologic enlargement of the uterus
during pregnancy occurs as a consequence of estrogen-stimulated smooth
muscle hypertrophy and smooth muscle hyperplasia
• The striated muscle cells in both the skeletal muscle and the heart can
undergo only hypertrophy in response to increased demand because limited
capacity to divide (Weightlifter can develop a rippled physique only by
hypertrophy of individual skeletal muscle cells induced by an increased
workload)
• Pathologic cellular hypertrophy include the cardiac enlargement that occurs
with hypertension or aortic valve disease
Physiologic hypertrophy of the uterus during pregnancy
A. Gross appearance of a normal uterus (right) and a gravid uterus (left) that was removed for
postpartum bleeding
B. Small spindle-shaped uterine smooth muscle cells from a normal uterus. Compare this with (C)
large, plump hypertrophied smooth muscle cells from a gravid uterus (B and C, same magnification).
 Hyperplasia
• Hyperplasia : An increase in the number of cells
in an organ or tissue.
• Normal cells may become cancer cells. Before
cancer cells form in tissues of the body, the cells
go through abnormal changes called
hyperplasia and dysplasia.
• In hyperplasia, there is an increase in the
number of cells in an organ or tissue that
appear normal under a microscope. In
dysplasia, the cells look abnormal under a
microscope but are not cancer.
• Hyperplasia and dysplasia may or may not
become cancer.
Type of Hyperplasia (1/2)
1. Hormonal hyperplasia
The proliferation of the glandular epithelium of the female
breast at puberty and during pregnancy
2. Compensatory hyperplasia
Hyperplasia that occurs when a portion of the tissue is
removed or diseased. Example : A liver is partially resected,
mitotic activity in the remaining cells begins as early as 12
hours later, eventually restoring the liver to its normal
weight.
 Dysplasia
• Dysplasia means abnormal growth and differentiation.
• The term have a developmental pathology or oncologic meaning.
• Developmental pathology : To describe morphogenetic
abnormalities (eg : dysplastic kidneys).
• Oncology : To describe disorderly growth and maturation of cells
that are not normal but that are not obviously malignant
(premalignant condition, a precursor of invasive neoplasia.
Dysplasia can also be considered as a transitional stage linking
neoplasia to hyperplasia or metaplasia)
Type of Dysplasia
1. Squamous dysplasia of the cervix : Dysplasia may be
graded as mild, moderate, or severe(grade I, II, or III).
2. Liver cell dysplasia: Liver cell carcinomas arise at an
increased rate in cirrhosis caused by viral hepatitis B and C
Degeneration
• Degenerasi merupakan suatu perubahan keadaan secara fisika dan
kimia dalam sel, jaringan, atau organ yang bersifat menurunkan
efisiensinya.
• Degenerasi dapat diakibatkan dari penuaan dan disebabkan oleh
penyakit. Proses penuaan dapat terjadi akibat dari paparan radikal
bebas.
 Macular degeneration
• Macular degeneration, or age-related macular degeneration (AMD), is a
leading cause of vision loss in Americans 60 and older. It is a disease that
destroys your sharp, central vision.
• AMD affects the macula, the part of the eye that allows to see fine detail
• There are two types: wet and dry
1.Wet AMD happens when abnormal blood vessels grow under the
macula. These new blood vessels often leak blood and fluid. Wet AMD
damages the macula quickly. Blurred vision is a common early symptom.
2.Dry AMD happens when the light-sensitive cells in the macula slowly
break down and effected gradually lose central vision. A common early
symptom is that straight lines appear crooked.
 Metaplasia
Definition
• A reversible change in one adult cell type (epithelial or mesenchymal) is
replaced by another adult cell type.
• Metaplasia: change in phenotype of differentiated cells, often a response
to chronic irritation that makes cells better able to withstand the stress;
usually induced by altered differentiation pathway of tissue stem cells; may
result in reduced functions or increased propensity for malignant
transformation.
• In this type of cellular adaptation, cells sensitive to a particular stress are
replaced by other cell types better able to withstand the adverse
environment.
• Metaplasia is thought to arise by genetic "reprogramming" of stem cells
rather than trans differentiation of already differentiated cells.
 Anaplasia
• Anaplasia of tumor cells is defined as lack of differentiation. Adult somatic
cells are differentiated (express genes in a tissue-specific manner).
• Common features :
1. Pleomorphism: Variation in size and shape of nuclei
2. Hyperchromatic nuclei: The chromatin in the nuclei is increased in
amount and irregularly distributed (‘‘clumped’’)
3. Atypical mitoses: may be tripolar or multipolar, in contrast to bipolar
normal mitoses
4. High nuclear cytoplasmic ratio: Resembling embryonic cells
5. Bizarre cells: Including giant cells
Causes of Cell Injury (1/3)
1. Oxygen Deprivation. Hypoxia is a deficiency of oxygen, which
causes cell injury by reducing aerobic oxidative respiration. Hypoxia
is an extremely important and common cause of cell injury and cell
death.
2. Physical Agents. Physical agents capable of causing cell injury
include mechanical trauma, extremes of temperature burns and
deep cold), sudden changes in atmospheric pressure, radiation, and
electric shock
Causes of Cell Injury (2/3)
3. Chemical Agents and Drugs. Chemicals such as glucose or salt in
hypertonic concentrations may cause cell injury directly or by
deranging electrolyte homeostasis of cells. High concentrations of
oxygen is severely toxic. Trace amounts of agents known as
poisons,such as arsenic, cyanide, or mercuric salts, may destroy
sufficient numbers of cells within minutes to hours to cause death.
4. Infectious Agents.
These agents range from the submicroscopic viruses to the large
tapeworms (rickettsiae, bacteria, fungi, and higher forms of parasites)
Causes of Cell Injury (3/3)
5. Immunologic Reactions. Immune reactions, cause cell injury. The anaphylactic
reaction to a foreign protein or a drug is a prime example, and reactions to
endogenous self-antigens are responsible for a number of autoimmune
diseases
6. Genetic Derangements. The genetic injury may result in a defect as severe as
the congenital malformations associated with Down syndrome, caused by a
chromosomal abnormality, or as the decreased life of red blood cells caused by
a single amino acid substitution in hemoglobin S in sickle cell anemia.
7. Nutritional Imbalances.Protein-calorie deficiencies cause an appalling number
of deaths. Nutritional problems can be self-imposed, as in anorexia nervosa or
self-induced starvation. Nutritional excesses also become important causes of
cell injury. Excesses of lipids predispose to atherosclerosis, and obesity is a
manifestation of the overloading of some cells in the body with fats.
Necrosis (1/3)
• The term necrosis was first used by morphologists to refer to a series
of changes that accompany cell death, largely resulting from the
degradative action of enzymes on lethally injured cells.
• Necrotic cells are unable to maintain membrane integrity, and their
contents often leak out.
• The enzymes responsible for digestion of the cell are derived either
from the lysosomes of the dying cells themselves or from the
lysosomes of leukocytes that are recruited as part of the
inflammatory reaction to the dead cells
• Necrosis of a collection of cells in a tissue or an organ, for instance in
the ischemic myocardium, results in death of the entire tissue and
sometimes an entire organ.
Type of Necrosis (1/2)
1. Coagulative necrosis is a form of tissue necrosis in which the component
cells are dead but the basic tissue architecture is preserved for at least
several days
2. Liquefactive necrosis is seen in focal bacterial or, occasionally, fungal
infections, because microbes stimulate the accumulation of
inflammatory cells and the enzymes of leukocytes digest ("liquefy") the
tissue.
3. Gangrenous necrosis is cell death applied to a limb, generally the lower
leg, that has lost its blood supply and has undergone coagulative necrosis
involving multiple tissue layers. When bacterial infection is
superimposed, coagulative necrosis is modified by the liquefactive action
of the bacteria and the attracted leukocytes (so-called wet gangrene).
Type of Necrosis (2/2)
4. Caseous necrosis is encountered most often in foci of tuberculous infection. The
term "caseous" (cheese-like) is derived from the friable yellow-white appearance
of the area of necrosis
5. Fat necrosis : Refers to focal areas of fat destruction, typically resulting from
release of activated pancreatic lipases into the substance of the pancreas and the
peritoneal cavity (acute pancreatitis).Pancreatic enzymes that have leaked out of
acinar cells and ducts liquefy the membranes of fat cells in the peritoneum, and
lipases split the triglyceride esters contained within fat cells.
6. Fibrinoid necrosis is a special form of necrosis usually seen in immune reactions
involving blood vessels. This pattern of necrosis is prominent when complexes of
antigens and antibodies are deposited in the walls of arteries. Deposits of these
"immune complexes," together with fibrin that has leaked out of vessels, result in
a bright pink and amorphous appearance in H&E stains, called "fibrinoid" (fibrin-
like) by pathologists
Homework : Case Report and Resume
1. Athropy
2. Hypertrophy& hyperplasia
3. Degeneration
4. Metaplasia
5. Dysplasia
6. Anaplasia
7. Necrosis