POTATO

NOTES PATHOLOGY LECTURE NOTES FIRST SHIFTING

CELLULAR ADAPTATION, INJURY, DEATH,
G2 M G0
Terminally
AND NECROSES Differentiated
Lecturer: Alita B. Santos, M.D., F.P.S.P. Continuously

SOURCES: Robins, PPT, Lecture Notes

cycling
G0
INTRODUCTION
S G1 Facultative
dividers

G0 Phase terminally differentiated cells

G1 Phase Gap Phase 1 longest phase
G2 Phase Gap Phase 2
M Mitotic Phase
S Synthesis Phase double amount of DNA
and RNA
o More proteins in the nucleus making
it hyperchromatic and larger

FACTS OR PRINCIPLES Labile cells continuously cycling cells
o e.g. epithelial cells, blood cells
1. Homeostatic state of cell is dependent on its Stable cells - facultative dividers
environment. o Only divide when needed
2. Change of environment above or below the o E.g. Fibroblasts, liver cells, bone
normal causes stress on the cell. cells, smooth muscle cells
3. Type of response depends on the Permanent cells terminally differentiated
characteristics of the stimulus. cells
4. Type of response depends on the quality of o Stay in the G0 phase
the cell at the time the stimulus is applied. o But, when stimulated, cells will try to
5. Response is either reversible or irreversible. divide go to S phase but cannot
enter the M phase because they do
HOMEOSTASIS used by physiologists to mean not have centrioles
maintenance of nearly constant conditions in the
internal environment *Labile and stable cells have basal cells/stem cells
Steady state on the basement membrane which are capable of
Feedback mechanisms dividing

EFFECTS OF A STRESSFUL STIMULUS ON A ADAPTATIONS OF CELLULAR GROWTH AND

CELL DEPEND ON: DIFFERENTIATION

1. Severity ADAPTATIONS
2. Duration reversible, functional and structural responses
3. Health of cell to changes in physiologic states (e.g.
4. Type of cell pregnancy) and some pathologic stimuli
reversible changes in size, number, phenotype,
FACTORS DETERMINING CELL RESPONSE TO metabolic activity, or functions of cells in
STRESS response to changes in their environment

1. Capacity to activate cells potentials MECHANISMS OF ADAPTATION

2. Availability of O2 and nutrients
3. Capacity to divide 1. Increasing cellular activity
a. Size hypertrophy
CELL CYCLE b. Number hyperplasia
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 POTATO NOTES PATHOLOGY LECTURE NOTES FIRST SHIFTING

c. If the cells are capable of dividing (labile or o Hormone-induced estrogen levels
stable cells) initially undergo hypertrophy during pregnancy massive
and then later hyperplasia physiologic growth of uterus
2. Decreasing cellular activity and cell size
atrophy
3. Altering cellular structure metaplasia

HYPERTROPHY

Increase in the size of cells, that results in an

increase in the size of the affected organ
o No new cells, just larger cells
o Due to synthesis and assembly of
additional intracellular structural Heart. Left (L): Normal cardiomyocytes; Right (R):
components Hypertrophied cardiomyocytes; Pointed red: squared out
Increased production of cellular nucleus
proteins
Increased RNA and DNA in
nucleus
Increased amount of cytoplasm
Cells capable of dividing - may undergo both
hyperplasia and hypertrophy
Pure hypertrophy without hyperplasia occurs
in terminally differentiated cells (heart and
skeletal muscle) Hyperchromatic, enlarged, squared out
Can be physiologic or pathologic nuclei
Physiologic - caused by increased functional Wider diameter of fibers
demand or by stimulation by hormones and Need more mitochondria because of
growth factors increased workload
o Increased workload most common Cardiomyocytes (for contractility) will need
stimulus for muscle hypertrophy more actin and myosin (myofilaments)
o E.g. hypertension or faulty valves amount of force each myocyte can
chronic hemodynamic overload generate strength and work capacity of
hypertrophy of heart the muscle
Increased endoplasmic reticulum
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Ventricular hypertrophy still has low oNeed for compensatory increase
cardiac output (CO) because of smaller after damage or resection
lumen of the left ventricle o Compensatory hyperplasia liver
regeneration after partial
Cardiac hypertrophy eventually reaches a hepatectomy
limit beyond which enlargement of muscle mass o Hormonal hyperplasia - female
is no longer able to cope with the increased breast at puberty and pregnancy
burden lysis and loss of myofibrillar in estrogen in no. of
contractile elements myocyte death can also cells in the endometrium and
occur breasts
o Net result cardiac failure in TSH demand for T3
and T4 from thyroid gland
follicular cells follicular
cells undergo hyperplasia
o in functional demand
Bone marrow in chronic
blood loss for blood cell
production
Secondary polycythemia
Lymph node hyperplasia
occurs when there are
infections in the body
size of the germinal
centers of the lymph
node
o Persistent cell injury
Pathologic hyperplasia
o Caused by excessive or
inappropriate actions of hormones or
growth factors
o Hyperplasia is distinct from cancer
but it is a fertile soil in which
cancerous proliferations may
eventually rise
o Hormone-induced endometrial
Physiologic hypertrophy of the uterus during pregnancy. .
hyperplasia
(A) Gross appearance of a normal uterus (right) and a gravid
uterus (removed for postpartum bleeding) (left). (B) Small When balance between
spindle-shaped uterine smooth muscle cells from a normal estrogen and progesterone is
uterus, compared with (C) large plump cells from the gravid disturbed absolute in
uterus, at the amount of estrogen
same magnification.
hyperplasia of endometrial
HYPERPLASIA
glands abnormal
menstrual bleeding
Increase in the number of cells in an organ
o Benign prostatic hyperplasia in
or tissue in response to a stimulus
response to hormonal stimulation by
Only take place if the tissue contains cells androgens
capable of dividing Abnormal but controlled
Physiologic hyperplasia Hyperplasia regresses if
o Due to action of hormones or growth hormonal stimulation is
factors eliminated
o Need to increase functional capacity
of hormone sensitive organs
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o Virally induced hyperplasia
papillomaviruses cause skin
warts and mucosal lesions
composed of masses of hyperplastic
epithelium

Thyroid Gland
Hypertrophy - tall columnar follicular cells
Hyperplasia
o all cells stay on the basement
membrane but due to the in
number of cells BM is elongated
and stretched out this is why
intraluminal projections are present Prostate gland. Red arrow: glands; Blue arrow: stroma
Due to TSH, follicular cells will uptake the
resting T3 and T4 from the colloid and Hypertrophy and hyperplasia
convert these into active forms result in Proliferation of both glandular structure and
scalloping of colloid fibromuscular stroma

Endometrium
Normal endometrium in proliferative phase
almost uniform diameter of endometrial
glands
In Hyperplastic endometrium some glands
A B are dilated
o Greater glandular lumen because of
the stretched out basement
membrane due to the hyperplasia
o in number of nuclei in the
endometrial stroma
o in number of the stromal cells and
glandular cells

C D
Thyroid gland. (A) and (C) normal thyroid gland specimen;
(B) and (D) hypertrophied and hyperplastic follicular cells

Prostate Gland

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 POTATO NOTES PATHOLOGY LECTURE NOTES FIRST SHIFTING

Post-partum uterus larger and has thicker

myometrium
o Stimulus: progesterone
o After fertilization of the egg
corpus luteum of pregnancy is
formed corpus luteum of
pregnancy produces progesterone
causes hypertrophy and
hyperplasia of the uterus
A Later on, the syncytiotrophoblasts in the
placenta are the ones that will produce the
progesterone

ATROPHY
Reduction in the size of an organ or tissue
due to a decrease in cell size and number
Always together with in fibrous connective
tissue (not surefrom lecture)
o cell size organ becomes fibrotic
B can become nodular
Physiologic atrophy
o Common in normal development
o E.g. embryonic structures
(notochord, thyroglossal duct)
undergo atrophy during fetal
development
o Decrease in size of uterus after
parturition
Pathologic atrophy
o Causes:
C o Reduced functional demand/
Endometrium. (A) Normal endometrium in proliferative phase; workload (atrophy of disuse)
(B) and (C) Hyperplasia of the endometrium; E.g. complete bed rest,
Blue arrow: dilated endometrial glands
fractured bone immobilized in
cast skeletal muscle
Post-Partum Uterus
atrophy
Initial decrease in cell size
reversible
More prolonged disuse
skeletal muscle fibers and
size
o Denervation atrophy
Normal metabolism and
function of skeletal muscle
depends on the nerve supply
Damage to the nerve leeads
to atrophy
o Diminished blood supply
Uterus. Above: normal uterus; Below: uterus after giving birth

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Ischemia as a result of slowly

developing arterial occlusive
disease atrophy of tissue
Brain progressive atrophy
because of blood supply
due to atherosclerosis (senile
atrophy)
o Inadequate nutrition/Malnutrition
Protein-calorie malnutrition
(marasmus) use skeletal
muscle protein as source of
energy after other reserves
have been depleted
muscle wasting/cachexia
muscle atrophy
o Loss of endocrine stimulation
Loss of estrogen stimulation
after menopause
physiologic atrophy of
endometrium, vaginal
epithelium and breast
o Pressure
Enlarging benign tumor
compresses surrounding
tissue ischemia atrophy
of surrounding tissues
Fundamental cellular changes: cell size Testis. (A) Testis, gross. Left: normal. Right: testis that has
and organelles metabolic needs of cell undergone atrophy; (B) testis with residual normal tubules
sufficiently to permit its survival (blue arrow) with active spermatogenesis, and focal atrophy of
some tubules (red arrow)
diminished function but cell death is minimal
This could occur in cryptorchidism
o Bring into balance the cells
(undescended testis)
metabolic demands and the lower
temperature could also lead to atrophy
blood supply, nutrition, or trophic
of the testis
stimulation new equilibrium is
achieved No proper spermatozoa produced
Atrophy caused by blood supply may
Skeletal Muscle
progress to irreversible injury and die
(apoptosis)

Atrophy. Normal cells Atrophy by reduction in cell size

Atrophy by reduction in cell number

Testis

Skeletal muscle. Red arrow: atrophic muscle cell

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In normal skeletal muscle cells, the cells are Normal ciliated columnar
almost of uniform sizes cells of trachea and bronchi
Atrophic skeletal muscle cells are not of are replaced by stratified
the same sizes squamous epithelial cells
o Causes: Although epithelial lining
Malnutrition becomes tough, important
Patient with spinal cord injury mechanisms of protection
Poliomyelitis against infection (i.e. mucus
Denervation secretion and ciliary action)
Disuse are lost.
Aging o Excretory ducts (e.g. pancreas, bile
duct) normally lined by secretory
Brain columnar epithelium presence of
Atrophic brain has wider sulci and stones in ducts squamous
narrower gyri metaplasia
Seen in old age o Chronic infection in cervix lead to
squamous metaplasia of
endocervical glandular epithelium
Influences that predispose to metaplasia
can initiate malignant transformation in
metaplastic epithelium
Squamous to columnar metaplasia
o Barrett esophagus
Refluxed gastric acid
Esophageal squamous
epithelium replaced by
intestinal-like columnar cells
Connective tissue metaplasia
o Formation of cartilage, bone, or
Brain. Wider sulci and narrower gyri adipose tissue in tissues that
normally do not contain these
Endometrium elements
Atrophic - Thinned out o Myositis ossificans bone
o Lined by cuboidal cells instead of tall formation in the muscle
columnar cells Metaplasia by reserve cell hyperplasia
o Has less glands o Reprogramming of stem cells known
o More fibrous tissue to exist in normal tissues
o Stem cells differentiate to a
METAPLASIA particular lineage brought about by
Reversible change in which one signals generated by cytokines,
differentiated cell type (epithelial or growth factors, and extracellular
mesenchymal) is replaced by another cell matrix
type
represents an adaptive response in which Metaplasia of columnar to squamous epithelium
one cell type that is sensitive to a particular
stress is replaced by another cell type that
is better able to withstand the adverse
environment
Columnar to squamous
o Columnar bronchial epithelium into
squamous epithelium in smokers
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Reserve cell hyperplasia

Differentiation of basal
cells to squamous
epithelium

Normal ciliated Basal cell hyperplasia

columnar epithelium
with layer of basal cells Loss of organization,
differentiation and
maturation of cells Metaplasia by reserve hyperplasia. (A) Normal columnar
cells (blue) with layer of basal cells (red); (B) Basal cell
hyperplasia (red); (C) Differentiation of basal cells into
squamous epithelium (red); (D) Loss of organization,
differentiation and maturation of cells, more prominent stratified
squamous epithelium instead of the normal simple columnar
epithelium

Bronchus

Metaplasia of columnar epithelium (blue) to squamous

epithelium (yellow) in a bronchus

Endocervix

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iii. Insulin-like growth factor
b. Suppressor factors
i. Contact inhibition
ii. Suppressor factors

REVERSIBLE AND IRREVERSIBLE INJURY

CELL INJURY
Results when cells are stressed so severely
that they are no longer able to adapt or
when cells are exposed to inherently
damaging agents
Endocervix, squamous metaplasia. (Blue) Normal simple
columnar epithelium; (Red) Squamous Metaplasia Not sure if CELLULAR RESPONSES TO INJURY
endocervix talaga itong slide na ito Reversible injury (Sublethal cell injury)
Cell death
Normal: tall columnar epithelium o Necrosis
But due to reserve cell hyperplasia, the o Apoptosis
epithelium is stratified squamous Subcellular alterations and cell inclusions
squamous metaplasia Intracellular accumulations
Have crypts or glandular structures Pathologic calcifications
(compared to the ectocervix)
CAUSES OF CELL INJURY
DISTAL ESOPHAGUS
Hypoxia
Lined normally by stratified squamous o Causes injury by aerobic oxidative
epithelium respiration
Due to repeated regurgitation metaplasia o Ischemia, cardiorespiratory failure,
occurs and it becomes lined with columnar oxygen-carrying capacity of blood
cells with cells capable of producing mucin (anemia), severe blood loss
(Barrett esophagus) o Depending on hypoxic state cells
may adapt, undergo injury or die
Physical agents
o trauma, extreme temperature,
radiation, electric shock
Chemical agents
o Glucose or salt in hypertonic
concentrations, poisons (arsenic,
cyanide, mercuric salt), O2 at high
amounts, pollutants, industrial and
occupational hazards
Infectious agents
Distal Esophagus. (Blue) normal epithelium, o viruses, tapeworms, bacteria, etc.
stratified squamous; (Red) metaplastic epithelium,
columnar cells
Immunologic Reactions
o Injurious reaction to endogenous
CONTROL MECHANISMS OF ADAPTATION self-antigens autoimmune
1. Limits of adaptation diseases
a. Growth factors o Immune reactions to viruses and
i. Epidermal growth factor environmental substances
ii. Platelet-derived growth factor Genetic derangement

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o Single base pair substitution Cytoskeletal filaments conglomerate in
amino acid substitution (e.g. sickle one side
cell anemia) o Other areas will have less
Nutritional imbalances cytoskeleton produce blebs
o Protein-calorie deficiencies, vitamin Lysosomes
deficiencies, nutritional excesses o will fuse with exhausted
mitochondria and other organelles
autophagy lead to formation of
REVERSIBLE INJURY lipofuscin pigment (wear and tear
Normal cell can undergo sublethal or pigment)
reversible changes when there is an o Autophagy starved cells eats its
injurious agent present own components in an attempt to
Hallmarks: decrease the nutrient demand to
o reduced oxidative phosphorylation match supply
ATP o Initially, lysosomes are membrane-
o cellular swelling bound
Two features recognized under light o If these burst, the lysosomal
microscope enzymes will be released in the
o Cellular swelling cytoplasm
Cells are incapable of Fate of the Nucleus
maintaining ionic and fluid o Heterochromatin- clumping
homeostasis
First manifestation in almost
all forms of injury to cells
Whole organ level - causes
pallor, turgor, weight of
organ
Microscopic small clear
vacuoles are seen
Also called hydropic change
or vacuolar degeneration 1
o Fatty change
Occurs in hypoxic injury and
toxic/metabolic injury
Mainly in hepatocytes and
myocardial cells
Plasma membrane alterations
o Blebbing, blunting, loss of microvilli
Mitochondria
o will have anaerobic respiration as
the main source of energy
o ATP levels in the cell
o Activity of active pumps such as
Morphologic changes in reversible cell injury and cell
the Na/K ATPase increased Na injury. (A) Normal kidney tubules with viable epithelial cells,
and other ions within the cell (B) Early (reversible) ischemic injury showing surface blebs,
osmosis or movement of water into increased eosinophilia of cytoplasm, and swelling of occasional
the cell swelling cells, (C) Necrosis (irreversible) of epithelial cells, with loss of
nuclei, fragmentation of cells, and leakage of contents
ER also swollen
o Some of the ribosomes fall off from
NECROSIS AND APOPTOSIS
the ER

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Nucleus Pyknosis Fragmentation
karyorrhexis into nucleosome-
karyolysis size fragments

Plasma Disrupted Intact; altered

membrane structure
especially
orientation of
lipids

Cellular Enzymatic Intact; may be

contents digestion; may released in
leak out of cell apoptotic bodies

Physiologic Invariably Often physiologic,

Necrosis Apoptosis or pathologic means of
pathologic (culmination of eliminating
Stimulus Hypoxia, Physiologic and role irreversible unwanted cells;
toxins pathologic cell injury) may be pathologic
after some forms
Histology Cellular Single cells of injury especially
swelling DNA damage
Chromatin
Coagulation condensation
necrosis
Apoptotic bodies
NECROSIS
Disruption of
organelles Spectrum of morphologic changes that
follow cell death in living tissue; differentiate
DNA Random, Internucleasomal from autolysis and apoptosis
breakdown diffuse Morphologic patterns: coagulative,
mechanisms Gene activation
liquefactive, caseous, enzymatic fat,
ATP depletion fibrinoid
Endonuclease
Accidental and unregulated form of cell
Membrane
death
injury Unable to maintain membrane integrity
contents often leak out inflammation in
Free radical surrounding tissue
damage Damage to membranes is severe
lysosomal enzymes enter cytoplasm
Tissue Inflammation No inflammation digest the cell
reaction Earliest histologic evidence of myocardial
Phagocytosis of
necrosis does not become apparent until 4-
apoptotic bodies 12 hours later
o But because the loss of the plasma
Cell size Enlarged Reduced membrane integrity cardiac-
(swelling) (shrinkage) specific enzymes and proteins are
rapidly released from necrotic
muscle detected in the blood as
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early as 2 hours after myocardial cell the proteolysis of dead cells
necrosis anucleate cells persist for days or
Nuclear changes (irreversible weeks
injury/necrosis) If the cell is striated, at first the striations are
o Clumped small nucleus still visible but later on the striations will no
Pyknosis characterized by longer be visible
nuclear shrinkage and Anything with hypoxia as the stimulus will
increased basophilia lead to coagulative necrosis EXCEPT for
Hyperchromatic the brain (liquefactive necrosis)
Karryolysis bassophilia of Necrotic cells are removed by phagocytosis
chromatin fades reflecting of the cellular debris by infiltrating
the loss of DNA because of leukocytes
enzymatic degradation by
endonucleases
Karyorrhexis pyknotic
nucleus undergoes
fragmentation
Loss of glycogen particles more glassy
homogenous appearance than normal cells
Myocardial infarct. Note that some cells no longer have nuclei

Ultrastructural features of reversible and irreversible

injury (necrosis). (A) normal epithelial cell of the proximal
kidney tubule; note abundant microvilli, (B) epithelial cell with
early cell injury; microvilli are lost, blebs are formed, (C) late
injury (irreversible), swollen mitochondria with electron-dense
deposits

COAGULATIVE NECROSIS
Stimulus: ischemia/hypoxia
E.g. Myocardial infarct
Coagulative necrosis. (A) wedge-shaped kidney infarct
Outline/architecture of cells still seen but no
(yellow), (B) microscopic view of the edge of infarct, with
more nucleus normal kidney (N) and necrotic cells in the infarct (I) showing
o Injury denatures not only structural the preserved cellular outlines with loss of nuclei and an
proteins but also enzymes blocks inflammatory infiltrate

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Pathologic stimulus for other organs:
CASEOUS NECROSIS pyogenic organism (Beta helomytic
Most often in foci tuberculosis infection Streptococcus sp., Staphylococcus sp.)
Caseous cheese-like because of the Always occurs with inflammation
friable white appearance of the area of When contained within a fibrous capsule
necrosis abscess
Necrotic area appears as a structureless Architecture of cells no longer visible
collection of fragmented or lysed cells and The area with necrosis is replaced by
amorphous granular debris enclosed with a inflammatory cells, neutrophils (violet), and
distinctive inflammatory border, which is necrotic debris (pink)
known as a granuloma Characterized by digestion of dead cells
Tuberculosis Mycobacterium tuberculosis resulting in transformation of the tissue into
Caseous central necrosis with granuloma a liquid viscous mass
(border) automatically Tuberculosis Focal bacterial or fungal infections
Pink amorphic material necrotic debris microbes stimulate the accumulation of
Note: the necrotic debris is more abundant leukocytes and the liberation of enzymes
in the caseous than in the liquefactive from these cells
necrosis Necrotic material creamy yellow
presence of dead leukocytes (pus)

Caseous necrosis. TB of the lung with a large area of

caseous necrosis containing yellow-white and cheesy debris

Caseous necrosis, cavitary lung lesion. Caseous

central necrosis (red) with granuloma (blue), the pink
amorphic materials are the necrotic debris, other cells are
the lymphocytic cells, macrophages Liquefactive necrosis. (A) Brain; (B) Liver abscess with
fibrous capsule (red)
LIQUEFACTIVE NECROSIS
For the brain, the stimulus is hypoxia GANGRENOUS NECROSIS

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Usually applied to a limb that has lost its
blood supple and has undergone necrosis APOPTOSIS
(coagulative necrosis) + when bacterial Programmed cell death
infection is superimposed there is more Tightly regulated; occurs normally
liquefactive necrosis Purpose: to remove unwanted aged or
potentially harmful cells
ENZYMATIC FAT NECROSIS Becomes pathologic event when diseased
Cause: Acute hemorrhagic pancreatitis cells become damaged beyond repair & are
sudden release of enzymes (lipases) from eliminated
the pancreas into the peritoneal cavity Apoptotic bodies resulting fragments
Released lipases split the triglyceride esters (contain portions of cytoplasm & nucleus) of
contained within the fat cells. The fatty acids the apoptotic cells; becomes more viable for
combine with calcium to produce grossly phagocytosis
visible chalky-white areas (fat No leakage of contents due to rapid
saponification) phagocytosis DOESNT elicit
inflammatory reaction (unlike necrosis)
When cells DNA or proteins are damaged
beyond repair cell kills itself apoptosis
Nuclear dissolution, fragmentation of cell
without complete loss of membrane
integrity, rapid removal of cellular debris
Cellular contents do not leak out (unlike
necrosis) no inflammatory reaction

CAUSES OF APOPTOSIS
Apoptosis in Physiological Situation
Omentum. (Blue) normal adipocytes, (red) adipocytes Apoptosis is a normal process
which have undergone enzymatic fat necrosis Serves to eliminate cells that are no
longer needed, to maintain a steady
FIBRINOID NECROSIS number of various cell populations in
Usually in immune reactions involving blood tissues
vessels Important in the ff. situations:
Occurs when complexes of antigens and o Destruction of cells during
antibodies are deposited in the walls of the embryogenesis
arteries o Involution of hormone-dependent
tissues upon hormone
withdrawal
endometrial breakdown
during menstruation
ovarian follicular atresia
in menopause
regression of the lactating
breast after weaning
prostatic atrophy after
castration)
o Cell loss in proliferating
populations as to maintain a
constant number (homeostasis)
Fibrinoid necrosis in an artery. The wall of the artery shows o Elimination of potentially harmful
circumferential bright pink area of necrosis with inflammation self-reactive lymphocytes to

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prevent rxns against ones own Phagocytosis of apoptotic cells or cell
tissues bodies, usually by macrophages
o Death of host cells after they Plasma membranes remain intact until the
have served their purpose: last stages when they become permeable to
Neutrophils (acute inflammatory normally retained solutes
response) & Lymphocytes (end
of immune response) Mechanisms of Apoptosis
Apoptosis results from the activation of
Apoptosis in Pathologic Conditions enzymes called caspases (cysteine
Eliminates cells that are injured beyond proteases that cleave proteins after aspartic
repair (repair mechanisms cant cope up residues)
with injury)
Death by apoptosis is responsible for
loss of cells in a variety of pathologic
states:
o DNA damage
Cytotoxic anticancer
drugs , hypoxia
Elimination of the cell
maybe a better
alternative than risking
mutations in the
damaged DNA, w/c may
result in malignant
transformation
o Accumulation of misfolded
proteins Phases of apoptosis
Basis of several
degenerative diseases of Execution phase
the CNS & other organs o Shrinkage of cell
o Cell death in infections o Chromatin condensation
viral infections) o Organelles are intact
o Pathologic atrophy in o Chromosome cleavage into
parenchymal organs after duct nucleosome fragments
obstruction o Loss of microvilli

MORPHOLOGY & BIOCHEMICAL CHANGES IN

APOPTOSIS

Morphologic features:
Cell Shrinkage
o cell is smaller in size
o dense cytoplasm
o organelles are tightly packed
Chromatin Condensation
o most characteristic feature of
apoptosis
o peripherally aggregated chromatin
o nucleus may break up
Formation of cytoplasmic blebs &
apoptotic bodies
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Loss of microvilli and Apoptotic body
junctions

B
Nuclear changes
fragmentation

Degradation phase.

Execution phase of apoptosis.

Phagocytosis
o No inflammation elicited
Degradation
o Mitochondria and organelles are
viable
o Apoptotic bodies are formed
because of the shrinking organelles

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Apoptotic body PRIMARY TARGETS OF INJURY AND DEATH
Cell membrane
Mitochondria
Cytoskeleton
Cellular DNA

MANIFESTED AS CYTOPLASMIC CHANGES

1. Cell swelling sublethal injury
2. Fatty change e.g. liver
3. Inclusions e.g. pigments

CELLULAR SWELLING
Swelling of mitochondria, ER, ribosomes fall
off
phagocytosis Seen in reversible injury
Nucleus is still intact
Causes ischemia, infections, chemicals
Occurs whenever cells are incapable of
maintaining ionic and fluid homeostasis
Result of failure of the energy-dependent
ion pumps
Small clear vacuoles represent the
distended and pinched off segments of the
ER vacuolar degeneration/hydropic
change

Phagocytosis.

NECROPTOSIS
A hybrid that shares aspects of both
necrosis and apoptosis
Resembles necrosis
o Loss of ATP
o Swelling of cells and organelles
o Generation of ROS
o Release of lysosomal enzymes
o Rupture of the plasma membrane
Resembles programmed cell death
o Triggered by genetically Cellular swelling. Ultrastructural changes
programmed signal transduction
Sometimes called programmed necrosis FATTY CHANGE
Fatty liver

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Common causes alcohol, malnutrition, o Accumulation of an abnormal
drugs substance as a result of genetic or
Hepatocytes with large lipid vacuoles (look acquired defects
like fat cells) o Failure to degrade a metabolite due
Different from the stromal infiltration of fat to enzyme deficiency
Occurs in hypoxic injury and various forms o Deposition and accumulation of
of toxic and metabolic injury abnormal exogenous substance
Appearance of lipid vacuoles in cytoplasm Fatty change/steatosis
o Different from the stromal infiltration
of fat
o Abnormal accumulations of
triglycerides within parenchymal
cells
o Occurs in the liver, heart, muscle,
kidney
o Causes: toxins, protein malnutrition,
diabetes mellitus, obesity, anoxia,
alcohol abuse
Proteins
o Appear as rounded, eosinophilic
droplets, vacuoles or aggregates in
the cytoplasm
o Reabsorption droplets in proximal
renal tubules
In renal diseases associated
with protein loss in the urine
Increased reabsorption of
protein into vesicles
o Russell bodies immunoglobulin in
plasma cells
o Alpha1-antitrypsin in liver cells
Glycogen
o Excessive intracellular deposits of
glycogen in patients with an
abnormality in either glucose or
glycogen metabolism
o Appear as clear vacuoles
o Diabetes mellitus prime example
Pigments
o Exogenous
Fatty Liver. Liver cells with large lipid vacuoles
Carbon black, coal dust
CELLULAR INCLUSIONS Picked up by
macrophages in
One of the manifestations of metabolic
alveoli transported
derangements in cells
through lymphatics
Four main pathways of abnormal
Accumulations
intracellular accumulations:
blackens tissue of the
o Inadequate removal of a normal
lungs (anthracosis)
substance due to defects in
packaging and transport Tattooing localized
Steatosis/fatty change in liver exogenous

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pigmentation of the o Alcoholic liver disease
skin o Nutritional deficiencies
o Endogenous o Mitochondrial myopathies
Hemosiderin-hemoglobin- Cytoskeletal abnormalities
derived yellow-to-brown o Chediak-Higashi syndrome, Immotile
granular pigment cilia syndrome
One of the storage o Mallori bodies, neurofibrillary tangles
forms of iron in Alzheimers disease
Lipofuscin- insoluble pigment
Wear-and-tear SUMMARY!!!!!!
pigment CELLULAR RESPONSES TO INJURY
Melanin
Bilirubin

PATHOLOGIC CALCIFICATION
Abnormal tissue deposition of calcium salts,
together with small amounts of iron,
magnesium, and other mineral salts
Calcium is often deposited at sites of cell
death resulting in pathologic calcification

1. Dystrophic calcification
a. Deposition occurs locally in dying
tissue
b. Alterations in areas of necrosis;
intracellular or extracellular or both
c. Psammoma bodies (papillary
carcinoma, carcinoma of ovary), in
atherosclerosis, aging, damaged
heart valves
2. Metastatic calcification
a. Deposition of calcium salts in ADAPTATION REVERSIBLE INJURY CELL DEATH
otherwise normal tissues resulting
from hypercalcemia
b. Associatedwith hyperparathyroidism, Adaptation, reversible injury, and cell death
Vit. D intoxication, systemic may be the stages of progressive impairment
sarcoidosis, milk-alkali syndrome, following different types of insults
hyperthyroidism, Addisons disease, When there is a change in physiologic states or
increased bone catabolism (tumors), pathologic stimuli are present adaptation
immobilization occurs upon elimination of the stress cell
can recover to its original state without having
SUBCELLULAR ALTERATIONS IN CELL suffered any harmful consequences
INJURY o If limits of adaptive responses are
Lysosomes: Heterophagy and autophagy exceeded cell injury occurs
o Lipofuscin pigments: residual Cell injury is reversible up to a
bodies, wear and tear pigments certain point
o Hereditary lysosomal storage If stimulus persists irreversible
disorders injury ultimately undergoes
o Acquired/iatrogenic storage disease cell death
Induction (hypertrophy) of SER Example: increase in hemodynamic load heart
muscle is enlarged (adaptation) if blood supply
Mitochondrial alterations
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 POTATO NOTES PATHOLOGY LECTURE NOTES FIRST SHIFTING

to myocardium is compromised reversible injury
irreversible injury cell death

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 POTATO NOTES PATHOLOGY LECTURE NOTES FIRST SHIFTING

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