Apoptosis cont

The cell's plasma membrane remains intact, but its structure is altered
in such a way that the apoptotic cell and its fragments become avid
targets for phagocytosis
The dead cell is rapidly phagocytosed and cleared, before its contents
have leaked out.
It occurs normally in many situations, and serves to eliminate unwanted
or potentially harmful cells and cells that have outlived their usefulness.
It is also a pathologic event when cells are damaged beyond repair,
especially when the damage affects the cell's DNA; in these situations,
the irreparably damaged cell is eliminated
Apoptosis in Physiologic Situations
 The programmed destruction of cells during embryogenesis
 Involution of hormone-dependent tissues upon hormone
deprivation. Eg endometrial cell breakdown during menstrual cycle
 Cell deletion in proliferating cell populations, eg. intestinal crypt
epithelia
 Death of host cells that have served their useful purpose, such as
neutrophils in an acute inflammatory response, and lymphocytes at
the end of an immune response.
03/25/2020
Apoptosis cont: mitochondrial pathway
Mitochondria contain several proteins that are capable of inducing
apoptosis including Cytochrome C
The permeability of the mitochondria is controlled by a family of more
than 20 proteins of which Bcl-2 is a prototype.
Bcl-2 activates 2 pro-apoptotic members of the family Bax and Bak .
These will dimerize, insert into the mitochondrial membrane, and form
channels through which cytochrome c and other mitochondrial proteins
escape into the cytosol.
Cytochrome c, together with some cofactors, activates caspase-9 which
ultimately leads to nuclear fragmentation
Necrosis
Necrosis refers to a spectrum of morphologic changes that follow cell
death in living tissue, due to degradative action of enzymes on the
injured cell.
It occurs in irreversible injury.
This may elicit inflammation in the surrounding tissue.
There is denaturation of intracellular proteins and enzymatic digestion
of the cell
The enzymes are derived either from the lysosomes of the dead cells
themselves, in which case the enzymatic digestion is referred to as
autolysis, or from the lysosomes of immigrant leukocytes, during
inflammatory reactions.
Types of necrosis cont
Feature Necrosis Apoptosis

Cell size Enlarged (swelling) Reduced (shrinkage)

Nucleus Pyknosis → karyorrhexis → Fragmentation into nucleosome size fragments

karyolysis

Plasma Disrupted Intact; altered structure, especially orientation of

membrane lipids

Cellular Enzymatic digestion; may leak Intact; may be released in apoptotic bodies
contents out of cell

Adjacent Frequent No
inflammation

Physiologic or Invariably pathologic Often physiologic, means of eliminating

pathologic role (culmination of irreversible cell unwanted cells; may be pathologic after some
injury) forms of cell injury, especially DNA damage
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 Cell injury responses
ADAPTIVE
 Hypertrophy - an increase in the size of the cell secondary
to an increase in cell function.
 Hyperplasia - an increase in the number of cells of a tissue
in response to a stimulus or injury.
 Metaplasia - replacement of one type of tissue with another
in response to an injury.
 Atrophy - decrease in the size and functional capacity of
the cell.
REVERSIBLE INJURY
IRREVERSIBLE INJURY - CELL DEATH
NECROSIS, APOPTOSIS
INTRACELLULAR ACCUMULATIONS AND PATHOLOGIC
CALCIFICATION
 Cellular adaptation
 Hyperplasia:- increase in the size or volume of an organ or
tissue due to increase in the number of the constituent
cells. It occurs in tissues with cells that can divide.
 Physiological:
 hormonal e.g. breast enlargement in pregnancy, puberty;
 low oxygen tension leads to bone marrow hyperplasia from
increased erythropoietin hormone or
 compensatory e.g. following partial hepatectomy.
The hormones stimulate growth directly or through stimulation
of growth factors.
 Cellular adaptation cont

 Pathological
This is due to excessive hormonal stimulation of growth factors
on target cells and the type that leads to disease. Eg. prostatic
hyperplasia in men.
It is a reversible process that may take place along with
hypertrophy because often the same stimulus can cause both
adaptive responses.
Pathologic hyperplasia is a fertile soil for cancers to arise.
 Cellular adaptation cont
 Hypertrophy ; increase size of tissue or organ due to
increase in size of individual cells.
No new cells are produced but the cells become larger by
synthesis of more structural components.
 Pysiological
 Due to increased functional demand as in skeletal muscle
hypertrophy due to exercise by athletes
 Hormones may cause physiological hypertrophy of muscle
as in pregnancy due to effect of estrogens;
 Pathological
 As in the heart hypertrophy in hypertension.
 prostatic enlargement in males.
 Cellular adaptation cont
Both hyperpasia and hypertrophy are present in pregnant
uterus and prostatic hyperplasia.
The cells increase the number of intracellular components e.g.
intracellular filaments in cardiac myocytes and skeletal
muscles in athletes. This enables an increased workload per
unit volume of cell not different from the normal cell. The
number of mitochondria also increase to supply more energy
for the increased activity. It is a reversible process.
 Cellular adaptation cont
 Atrophy:- decrease in size of tissue or organ due to
decrease in size or number of cells or both. Atrophy may
also apply to shrinkage of a cell due to loss of cell
substance so that when sufficient numbers are involved
then the size of the tissue or organ will be reduced.
The reduction in size of cells is due to autophagy a process
by which cellular components are digested by the cell’s own
lysozymes leading to reduction of cell constituents and cell
size. The persistence of the stimulus may lead to cell death-
apoptosis- and reduction in the number of cells in the organ.
 Physiological
 in embryonic life and after parturition affects uterus and in
old age affects the testes.
Cellular adaptation cont
 Pathological atrophy occurs as a result of
 Disuse or decreased workload (e.g. immobilized limb due
to a fracture),
 Loss of innervation leads to muscle atrophy,
 Loss or reduction of blood supply leads to atrophy of skin
or kidney,
 Pressure atrophy occurs when tissues are compressed.
 Also lack of hormones (reduced endocrine stimulation)
e.g. menopause affects breasts and endometrium.
 Lack of nutrition leads to atrophy of adipose tissue and
later skeletal muscle e.g. protein calorie malnutrition
(marasmus).
 Aging causes senile atrophy in tissues like brain and heart.
 Cellular adaptation cont

Micro: The cells show increased number of autophagic

vacuoles and residual bodies e.g. lipofuscin granules
Macro: small organ and lipofuscin may impart brown colour to
organs (e.g. brown atrophy of heart).
The atrophic cells are not dead but are at a lower level of
metabolism.
 Cellular adaptation cont

 Metaplasia is a reversible change in which one adult cell

type is replaced by another adult cell type.
It is adaptive change to replace cells that are sensitive to a
particular type of stress with types of cells better able to
withstand the stress.
E.g. Columnar cells to squamous in the respiratory tract in
chronic irritation by cigarette smoke. (Squamos metaplasia)
Squamous cells to glandular cells in lower esophagus due to
acid reflux from stomach.
If stimulus is persistent may induce cancers.