9/21/2011

Types of Cell Death

Necrosis
Pathologic cell death

Cell Death & Adaptations

Apoptosis
Programmed cell death (physiologic or
some times pathologic)

Types of Necrosis

Coagulative Necrosis (protein denaturation)

Liquefactive Necrosis (enzymatic catabolism)
Caseous Necrosis
Fat Necrosis
Gangrenous Necrosis
Fibrinoid Necrosis

Renal infarct -- gross

Coagulative Necrosis
Cells basic outline is preserved
(presumably due to denaturation of both
structural & enzymatic proteins)
Appearance-- Glassy homogeneous (loss of
glycogen granules),eosinophilic (loss of
cytoplasmic RNA) & opaque
Nuclear changes- pyknosis, karyorrhexis,
karyolysis or
Usually seen in hypoxic injury of solid organ
like spleen, heart & kidney

Splenic infarcts -- gross

9/21/2011

Myocardium photomic

Liquefactive Necrosis
Usually due to enzymatic dissolution of
necrotic cells (usually due to release of
proteolytic enzymes from neutrophils in
bacterial or fungal infections)
Necrotic area undergoes softening and
are filled with pigmented or turbid fluid
Complete loss of structure
Most often seen in CNS and in
abscesses

Liquefactive necrosis -- gross

Liquefactive necrosis of brain

-- micro

Liquefactive
necrosis of brain

Liver abscess -- micro

Caseous Necrosis
Gross: Creamy-cheese appearance,
slightly greasy to touch
Micro: Amorphous, granular eosinophilc
material surrounded by a rim of
inflammatory cells
No visible cell outlines tissue architecture
is obliterated

Commonly seen in tuberculosis

Liver abscess

9/21/2011

Caseous necrosis -- gross

Extensive caseous necrosis

-- gross

Enzymatic Fat Necrosis

Caseous necrosis -- micro

Results from hydrolytic action of lipases

on fat
Most often seen in and around the
pancreas due to escape of pancreatic
enzymes hydrolyzing triglyceride esters
Fatty acids released via hydrolysis react
with calcium to form chalky white areas
saponification
Can also be seen in other fatty areas of
the body, usually due to trauma
Shadowy cell outlines
(without nucleus & with insoluble soap deposits)

Enzymatic fat necrosis of

pancreas -- gross

Fat necrosis -- micro

9/21/2011

Gangrenous Necrosis
A complication of necrosis most often seen
on extremities, usually due to trauma or
physical injury e.g. diabetic foot
Necrotic tissue invaded by putrefactive
organisms & looks green or black
Dry gangrene no bacterial superinfection;
tissue appears dry---Coagulative necrosis
Wet gangrene bacterial superinfection;
tissue swells & looks wet---Coagulative
necrosis progressing to liquefactive one

Wet gangrene -- gross

Fibrinoid Necrosis
Usually seen in the walls of blood vessels
(e.g., in vasculitis)
Glassy, eosinophilic fibrin-like material is
deposited within the vascular walls

Gangrene -- gross

Gangrenous necrosis -- micro

Apoptosis
Involved in many processes, some
physiologic, some pathologic
Cell death during embryogenesis (organ
development & modeling)
Hormone-dependent involution or atrophy of
organs in the adult e.g. uterus, breast, prostate
Deletion of autoreactive T cells in thymus
Cell deletion in proliferating cell populations
(intestinal crypt epithelium)
Cell death in tumors
Mild injurious stimuli causing irreparable DNA
damage-p53

9/21/2011

Mechanism of Apoptosis

Apoptosis Morphologic Features

Cell shrinkage with increased
cytoplasmic density
Chromatin condensation
Formation of cytoplasmic blebs and
apoptotic bodies
Phagocytosis of apoptotic cells by
adjacent healthy cells

Four separable but overlapping

components
-signaling
-control & integration
-execution
-removal of dead cells

Comparison b/w Necrosis & Apoptosis

Necrosis

Events in apoptosis
Apaf-1
Cyt. c

Phagocytosis by
Macrophages or
adjacent epithelial cells

Intrinsic
embryogenic
signals
Transglutaminases
activation
Cross-linking

Not a programmed cell death

Always pathologic result of irreversible injury (detrimental or fatal)
Large number of cells die at a time (homicide) i.e. death of tissue or organ
Cells or tissue remain part of the body (often need surgical removal)
Mechanisms involved ATP depletion, free radical damage, membrane
injury etc.
DNA break down-Random
Inflammation

Apoptosis

Apoptosis Diagram

Programmed cell death

Mostly physiologic & beneficial (seldom pathologic)
Involved death of single cells or cluster of cells (suicide)
Dead Cells remain no more part of the body
Mechanism involved gene activation, endonucleases, proteases
l DNA break down-Internucleosomal
No inflammation

Cellular Adaptations
Hypertrophy
Hyperplasia
Atrophy
Metaplasia

9/21/2011

Slide Adaptation diagram

Hypertrophy
Increase in the size of cells leading to
an increase in the size of the organ
(often seen in tissues made up of
terminally differentiated cells they can
no longer divide, their only response
to the stress is to enlarge)
End result is that the amount of
increased work that each individual cell
must perform is limited
Can be either physiologic or pathologic

Hypertrophy (contd)
Physiologic
Due to hormonal stimulation (e.g.,
hypertrophy of uterine smooth muscle
during pregnancy)

Physiologic hypertrophy

Pathologic
Due to chronic stressors on the cells (e.g.,
left ventricular hypertrophy due to longstanding increased afterload such as HTN,
stenotic valves)

Chronic Hypertrophy

Myocyte adaptation

Chronic cardiac volume overload-neonatal

genes activated-contractile proteins shift
High DNA content due to cell cycle arrest
If the stress that triggered hypertrophy does
not abate, the organ will most likely proceed
to failure e.g. heart failure due to
persistently elevated HTN
Hypertrophied tissue is also at increased risk
for development of ischemia, as its
metabolic demands may outstrip its blood
supply

9/21/2011

Physiologic Hyperplasia

Hyperplasia

Hormonal
Increase in the number of cells in an
organ or tissue
May or may not be seen together with
hypertrophy
Can be either physiologic or pathologic

Hyperplasia of uterine muscle during

pregnancy or glandular epithelium of breast
at puberty and during pregnancy

Compensatory
Hyperplasia in an organ after partial
resection (e.g. liver) or wound healing

Mechanisms include increased DNA

synthesis-increased GF
Growth inhibitors will halt hyperplasia
after sufficient growth has occurred

Atrophy

Pathologic Hyperplasia
Due to excessive hormonal stimulation
Endometrial proliferation due to increased
absolute or relative amount of estrogen

Due to excessive growth factor stimulation

Warts arising from papillomaviruses-TF

Not in itself neoplastic or preneoplastic

but the underlying trigger may put the
patient at increased risk for developing
sequelae (e.g., dysplasia or carcinoma)

Shrinkage in the size of the cell due to

loss of cell substance (with or without
accompanying shrinkage of the organ or
tissue)
Atrophied cells are smaller than normal
but they are still viable they do not
necessarily undergo apoptosis or
necrosis
Can be either physiologic or pathologic

Atrophy (contd)
82 yrs old man

Physiologic

Physiologic atrophy
25 yrs old man

Tissues / structures present in embryo or in

childhood (e.g., thymus) may undergo atrophy as
growth and development progress

Pathologic

Decreased workload
Loss of innervation
Decreased blood supply
Inadequate nutrition
Decreased hormonal stimulation
Aging
Physical stresses (e.g., pressure)

9/21/2011

Metaplasia
A reversible change in which one
mature/adult cell type (epithelial or
mesenchymal) is replaced by another
mature cell type
If injury or stress abates, the metaplastic
tissue may revert to its original type

A protective mechanism rather than a

premalignant change

Squamous metaplasia

Metaplasia (contd)
Bronchial (pseudostratified, ciliated
columnar) to squamous epithelium
E.g., respiratory tract of smokers

Endocervical (columnar) to squamous

epithelium
E.g., chronic cervicitis

Esophageal (squamous) to gastric or

intestinal epithelium
E.g., Barrett esophagus

Gastric metaplasia in
esophagus -- micro

Metaplasia -- Mechanism
Reprogramming of epithelial stem cells
(reserve cells) from one type of epithelium
to another
Reprogramming of undifferentiated
mesenchymal (pluripotent) stem cells to
differentiate along a different
mesenchymal pathway