CELLULAR

ADAPTATION, CELL
INJURY, AND CELL
DEATH
CELLULAR ADAPTATION,
CELL INJURY, AND CELL
DEATH
 CELLULAR ADAPTATIONS OF GROWTH AND
DIFFERENTIATION
 CELL INJURY- CAUSES, MECHANISMS,
MORPHOLOGY, EXMAPLES
 APOPTOSIS
 SUBCELLULAR RESPONSES TO INJURY
 INTRACELLULAR ACCUMULATIONS
 PATHOLOGIC CALCIFICATION
 CELLULAR AGING
NATURE AND SEVERITY OF CELLULAR RESPONSE
INJURIOUS STIMULUS

1. ALTERED PHYSIOLOGIC 1. CELLULAR ADAPTATIONS:

STIMULI: – HYPERPLASIA,
– INCREASED DEMAND, HYPERTROPHY
INCREASED TROPHIC – ATROPHY
STIMULATION – METAPLASIA
– DECREASED NUTRIENTS,
STIMULATION
– CHRONIC IRRITATION
2. REDUCED OXYGEN SUPPLY; 2. CELL INJURY:
CHEMICAL INJURY; – ACUTE REVERSIBLE
MICROBIAL INFECTION INJURY
– ACUTE AND SELF- – IRREVERSIBLE INJURY-
LIMITED CELL DEATH:NECROSIS,
– PROGRESSIVE AND APOPTOSIS
SEVERE(INCLUDING DNA – SUBCELLULARALTERATIO
DAMAGE) NSIN VARIOUS
– MILD CHRONIC INJURY ORGANELLES
CELLULAR RESPONSES TO
INJURY

3. METABOLIC 3. INTRACELLULAR
ALTERATIONS, ACCUMULATIONS,
GENETIC OR CALCIFICATIONS
ACQUIRED
4. PROLONGED LIFE 4. CELLULAR AGING
SPAN WITH
CUMULATIVE
SUBLETHAL INJURY
CELLULAR ADAPTATIONS
OF GROWTH AND
DIFERENTIATION
HYPERPLASIA- an increase in the
number of cells in an organ or
tissue, usually resulting in increased
volume of the organ or tissue
1. Physiologic- hormonal, compensatory
2. Pathologic- excessive hormonal
 PATHOLOGIC
HYPERPLASIA
 Excessive hormonal simulation or growth
factors acting on target cells
 Endometrial hyperplasia
 Benign prostatic hyperplsia
 Also an important response of connective tissue
cells in wound healing, in which proliferating
fibroblasts and blood vessels aid in repaire
 Viral infections (HPV) causing skin warts and
number of mucosal lesions composed of masses
of hyperplastic epithelium
 HYPERTROPHY
 An increase of the size of cells, resulting
in an increase of size of the organ
 The synthesis of more structural
components
 In nondividing cells
 Have a higher DNA content than in normal
cells
 Increased workload-muscle cells; uterus
during pregnancy
 ATROPHY
Shrinkage in the size of the cell by loss of cell
substance
Causes:
1. Decreased workload
2. Loss of innervations
3. Inadequate nutrition
4. Loss of endocrine stimulation
5. Aging
6. Pressure
Kidneys, normal (left) and
ischemic atrophy (right) -
Gross, cut surfaces
 METHAPLASIA
 A reversible change in which one adult cell
type (epithelial or mesenchymal) is
replaced by another adult cell type
 Columnar to squamous (in the respiratory
tract, Barrett esophagus)
 Connective tissue metaplasia (formation of
cartilage, bone, adipose tissue in tissues
that normally do not contain this elements
(myositis ossificans)
 CELL INJURY-
OVERVIEW
 Reversible cell injury, when the damaging
stimulus is removed
 Irreversible injury and cell death-
apoptosis and necrosis
 Causes of cell injury: oxygen deprivation,
physical, chemical, biological agents,
immunologic reactions, genetic
derangements, nutritional imbalances
 MORPHOLOGY OF CELL
INJURY AND NECROSIS
 Cellular swelling (when it is connected with many
cells in an organ it causes pallor, increased
turgor, and increase in weight of the organ)
 Plasma membrane alterations (blebbing, blunting,
distortion of microvilli, creation of myelin
figures, loosening of intracellular attachments)

•
 MORPHOLOGY OF CELL
INJURY AND NECROSIS
 Mitochondrial changes (swelling,
rarefaction)
 Dilation of the endoplasmic reticulum
(detachment and disaggregation of
polysomes)
 Nuclear alterations (disaggregation
of granular and fibrillar elements)
 NECROSIS
Spectrum of morphology changes that
follow cell death in living tissue,
resulting from the progressive
degradative action of enzymes on the
lethally injured cells
 MORPHOLOGY
 Increased eosynophilia (more glassy
homogenous appearance than that of
normal cells, loss of glycogen
particles)
 Vacuolated cytoplasm and appearance
moth-eaten
  Myelin figures- large whorled
phospholipid masses, which replaced dead
cells
 Phagocytosis or degradation in fatty
acids
 Calcification (calcium soaps)
 Nuclear changes:
 Karyolysis (chromatin fade)
 Pyknosis (nuclear shrinkage and increased
basophilia)
 Karyorrehis (pyknotic or partially
pyknotic nucleus undergoes
fragmentation)
 NECROSIS
 Coagulative necrosis
 Liquefactive necrosis
 Caseous necrosis
 Fat necrosis
 Coagulative necrosis
Implies preservation of the basic outline of
the coagulated cells for a span of at least
some days; the affected tissue exhibit a
firm texture. The injury or increasing
intracellular acidosis denatures structural
proteins and enzymes and so blocks the
proteolysis of the cell (myocardial infarct)
 Liqueafective necrosis
 Characteristic of focal bacterial or
fungal infections (accumulation of
inflammatory cells)
 Central nervous system (hypoxia)
 The result is transformation of
tissue into a liquid viscous mass
Brain, old (cystic) infarct
 Caseous necrosis
Is a form of coagulative necrosis
(mainly is associated with
tuberculosis); the name is derived
from the cheesy white gross
appearance of the area of necrosis
Pulmonary
tuberculosis
 Fat necrosis
It is descriptive of focal areas of fat
tissue destruction, as a result of
release of activated pancreatic
lipases
APOPTOSIS
 DEFINITION
 A pathway of cell death
 Induced by tightly regulated
intracellular program in which cell
destined to die activate enzymes
that degrade the cells’ own nuclear
dna and nuclear and cytoplasmic
proteins
 CAUSES OF
APOPTOSIS
Apoptosis in physiologic situations
1. During embryogenesis
2. Hormone-dependent involution in the
adult
3. Cell deletion in proliferating cell
populations
4. Elimination of potentially harmful self -
reactive lymphocytes
5. Cell death induced by cytotoxic T cells
 APOPTOSIS IN
PATHOLOGIC
CONDITIONS
 Produced by a variety of injurious
stimuli (radiation, heat, hypoxia,
anticancer drugs)
 Cell injury in certain viral diseases
 Pathologic atrophy in parenchymal
organs after duct obstruction
 Cell death in tumors
 MORPHOLOGY
 Cell shrinkage
 Chromatin condensation
 Formation of cytoplasmic blebs and
apoptotic bodies
 Phagocythosis of apoptotic cells or
cell bodies, usually macrophages
 MECHANISMS OF
APOPTOSIS
 The extrinsic (death receptor-
initiated) pathway
 The intrinsic (mitochondrial) pathway
 The execution phase
 Removal of dead cells
 EXAMPLES OF
APOPTOSIS
 After growth factor deprivation
 Dna damage-mediated apoptosis
 Induced by tumor necrosis factor
family of receptors
 Cytotoxic T-lymphocyte-mediated
apoptosis
 SUBCELLULAR
RESPONSES TO INJURY
 Lysosomal catabolism (heterophagy,
autophagy)
 Hypertrophy of smooth endoplasmic
reticulum
 Mitochondrial alterations
 Cytoskeletal abnormalities
 SUBCELLULAR
RESPONSES TO INJURY
 Lysosomal catabolism (heterophagy,
autophagy)
 Hypertrophy of smooth endoplasmic
reticulum
 Mitochondrial alterations
 Cytoskeletal abnormalities
 Intracellular
accumulations
• A normal cellular constituent
accumulated in excess (water, lipids,
proteins, carbohydrates)
• Abnormal substance accumulation
(exogenous- infectious agents or
minerals; endogenous)
• pigments
 Mechanism of intracellular
accumulations
• A normal endogenous substance is produced
at a normal or increased rate, but the rate of
metabolism is inadequate to remove it
• A normal or abnormal endogenous substance
accumulates because of genetic or acquired
defects in the metabolism, packaging,
transport or secretion of the substances
• An abnormal exogenous substance is
deposited and accumulated assocuated with
the lack of enzymatic machinery to degrade
it
 Lipids
• Triglycedydes
• Cholesterol/cholesterol esters
• Phospholipids
• Steatosis (fatty change) abnormal
accumulations of triglycerydes within
the parenchymal cells
• Liver, heart, muscle, kidney
 Causes of the steatosis
• Toxins (including alkohol)
• Protein malnutrition
• Diabetes mellitus
• Obesity
• Anoxia
• Hipoxia
• Unproper blood supply
 LIPIDS
Steatosis morphology:
 Liver – development of minute, membrane-
bound inclusions (liposomes) closely applied to
the endoplasmic reticulum; it is observed as
small vacoules in the cytoplasm around the
nucleus
 Heart –small droplets, occurring as intracellular
deposits of fat, which create grossly apparent
bands of yellowed myocardium alterating with
bands of darker, redbrown, uninvolved
myocardium (tiggered effect)
Liver, fatty - Gross
Liver, fatty change -
Medium power
• Intracellular accumulations of a variety of
materials can occur in response to cellular
injury. Here is fatty metamorphosis (fatty
change) of the liver in which deranged
lipoprotein transport from injury (most
often alcoholism) leads to accumulation of
lipid in the cytoplasm of hepatocytes.
•
 staetosis
•
 Adipositas
. hypertrophia of the adipose tissue
surrounded the whole organs
• Pancreas, liver, heart, kidneys
•
 obesity
• As a sighn of the unproper diet –
exogenous obesity
• As a sighn of the ubnormal hormons
level- endogenous obesity
CHOLESTEROL
 Atherosclerosis
 Xanthomas
 Infflamation and necrosis
 Cholesterolosis
 Niemman-Pick disease
 atherosclerosis
• Atherosclerotic plaques, smooth
muscle cells and macrophages in the
intimal layer of the aorta and large
arteries are filed by lipid vacuoles
(cholesterol and cholesterol esters)
 xanthomas
• Intracellular accumulations in the
macrophages in hereditary
hyperlipidemic states
 Inflammation and
necrosis
• Foamy macrophages (phagocytosis of
the lipid membranes from the injured
cells)
 cholesterolosis
• Focal accumulations of cholesterol-
laden macrophages in the lamina
propria of the gallbladder
 PROTEINS
 Reabsorption droplets in proximal renal
tubules (proteinuria)
 Synthesis of excessive amounts of normal
secretory protein, as occurs in certain
plasma cells engaged in active synthesis of
immunoglobulin (Russell bodies)
 Defects in protein folding
HYALINE CHANGE
An alteration within cells or in the
extracellular space, which gives a
homogenous, glassy, pink appearance in
histologic staining (reabsorption
droplets, Russel bodies, Mallory
alcoholic hyaline)
• Cytoplasmic organelle damage leads to a variety of injury
patterns, most of which are best seen by electron
microscopy. Acute injuries tend to damage an entire cell, so
specific organelle damage is beside the point. However, in
some cases the damage can be cumulative over many years.
Here are Mallory bodies (the red globular material)
composed of cytoskeletal filaments in liver cells chronically
damaged from alcoholism. These are a type of
"intermediate" filament between the size of actin (thin) and
myosin (thick).
 GLYCOGEN
 Diabetes mellitus-glycogen is found in
the epithelial cells, hart mussle cells,
β cells of the islets of Langerhans
 Glycogen storage diseases
 glycogenoses
 PIGMENTS
 Exogenous pigments (carbon, coal
dust)
 Picked up by macrophages and
transported it on lymph nodes
 Tattooing
 PIGMENTS
 Endogenous pigments
 Lipofuscin (cytoplasmic, perinuclear, aging
pigment, particularly in liver and hart)
 Melanin (brown-black pigment in
melanocytes; alkaptonuria, ochronosis)
 Hemosiderin (hemoglobin-derived, granular
pigment in which form iron is stored in
cells)-in phgocytes of the bone marrow
splen, liver)
 Lipofuscin
• Lipofuscin is the name given to finely
granular yellow-brown pigment granules
composed of lipid-containing residues of
lysosomal digestion. It is considered one of
the aging or "wear and tear" pigments,
found in the liver, kidney, heart muscle,
adrenals, nerve cells, and ganglion cells. It
is specifically arranged around the nucleus.
•
•
 Anthracosis
• The accumulation of the coal dust in the
lung parechyma as well as the lymph nodes
near the trachea and bronchi
• chronic lung disease characterized by the
deposit of coal dust in the lungs and by the
formation of black nodules on the
bronchioles, resulting in focal emphysema.
The condition occurs in coal miners and is
aggravated by cigarette smoking.
 anthracosis
•
 anthracosis
•
•
• Exogenous
pigments
 PATHOLOGIC
CALCIFICATION

 Dystrophic calcification
 Metastatic calcification
 DYSTROPHIC
CALCIFICATION
 Encountered in areas of necrosis
 The calcium salts have a basophilic, granular or
clumped appearance; intra- or extracellular,
sometimes with heterotopic bone formation
 The progressive acquisition of outer layers may
create lamellated configurations, called
psammoma bodies
 Associated with atheromas, cells’ damage or
ageing
 Heart, aortic valve,
calcified aortic stenosis
 METASTATIC
CALCIFICATION
 Hypercalcemia: increased secretion of
PTH; destruction of bone tissue (leukemia,
multiple myeloma); diffuse skeletal
methastasis; vitamin D-related disorders;
renal failure
 It may occur throughout whole body,
especially in interstitial tissues of the
gastric mucosa, kidneys, lungs, systemic
arteries and pulmonary veins
Cellular aging