Professional Documents
Culture Documents
2. TYPES OF ADAPTATION
3. CELL INJURY TYPES (REVERSIBLE AND IRREVERSIBLE)
4. MORPHOLOGICAL CHANGES IN CELL INJURY
1. Gene activation
2. Increased protein synthesis
3. Increased organelles production within the cells.
4. Hormonal stimulation
5. Growth factor stimulation
6. Increased functional demand
❑ Hypertrophy usually occurs in permanent tissues
which cannot undergo cell division .
As the skeletal muscle , cardiac muscle
(myocardium) or neurons.
It can be Physiological as seen in skeletal muscle
during exercise , or in heavy weight lifters ..
❑ Or due to Hormonal stimulation : as in gravid
uterus during pregnancy , usually combined with
hyperplasia which is increase in cell number .
or Pathological due to
a- increased demand myocardial cells due to
hypertension , or aortic valve disease leading to
enlargement of the heart size induced by increase in
the size of myocardial cells .
b- Compensatory enlargement of residual viable
cardiac myocytes after myocardial infarction (MI) in
which the hypertrophy compensate for the death of
neighboring ischemic cells .
Dead cells,:
Nuclei are “
condensed &
dense
Nuclei break —^
up into fragments
Karyorrhexis
Nuclei are
di ssolved
Karyolysis
Greater
Omentum
Liver-
Stomach —
Gallbladder
Transverse
colon
underneath
Greater-——'
"3-omentum
CYTOSKELETAL
DAMAGE
CELL DEATH
(mainly by
apoptosis)
• Damage to Mitochondria
❖ Normally: mitochondria are the cell's mini
factories that produce a life —sustaining energy in
the form of ATP.
3. DNA fragmentation:
FR reactions with thymine in nuclear & mitochondrial DNA
produce single-strand breaks.
Such DNA damage has been implicated in both cell killing
& the malignant (cancer) transformation of cells.
• Defects in Membrane Permeability
❑ Membrane damage is a constant feature of most
forms of cell injury i. e. necrosis (except apoptosis).
(2)Heterophagy :
• Refers to ingestion of particles from outside the cell .
Example : carbon particles inhaled from the
atmosphere, or inoculated pigment in tattoos can be
phagocytosed by ( Heterophagy) they may persist in
phagolysosoms of macrophages for decades or more.
AUTOPHAGY
Primary lysosome
Primary
lysosome Ingested particle
Autophagic Phagocytic
vacuole vacuole
Receptor-ligand interactions
Fas
TNF receptor
Ligands for
phagocytic
cell receptors
Apoptotic body
Cytoplasmic bleb
© Elsevier. Kumar et al: Robbins Basic Pathology 8e - www.studentconsult.com
❑Apoptosis is mediated by proteolytic enzymes
called caspases, which trigger cell death by
cleaving specific proteins in the cytoplasm and
nucleus. Caspases exist in all cells as inactive
precursors, or procaspases, which are usually
activated by cleavage by other caspases, producing
a proteolytic caspase cascade.
Atherosclerosis: aorta
Atherosclerosis in aorta: microscopic view shows deposition of cholesterol &
cholesterol esters appear as white vacuoles within macrophages & smooth muscle
cells in the wall of blood vessel.
Figure 93 : Xanthelasma : Yellowish skin nodules ,
consisting of cholesterol filled subcutaneous lesions .
Figure 94 : Xanthoma of hands.
Figure 95 : Skin biopsy in xanthoma : showing foamy lipid-laden macrophages
filled with cholesterol (arrow) .
Proteins
(1) In disorders with heavy protein leakage across the
glomerular filter proteinuria, e.g., in nephrotic syndrome ,
there is marked increased pinocytic reabsorption of the protein,
resulting in the appearance of pink, hyaline cytoplasmic
droplets in the renal tubular epithelium .
The process is reversible ; if the proteinuria ends, the protein
droplets disappear.
(2) Marked accumulations of synthesized immunoglobulines in the
RER of some plasma cells, resulting Russell bodies.
Plasma cell
DNA damage :
❑ A variety of metabolic insults that accumulate overtime
may result in damage to nuclear & mitochondrial DNA .
Although most DNA damage is repaired by DNA repair
enzymes ,some persists and accumulates as cells age .
Decreased cellular replication :
❑ All normal cells have a limited capacity for
replication .and after a fixed number of divisions cells
become arrested in a terminally non dividing state ,
known as replicative senescence .
❑ Aging is associated with progressive replicative
senescence .
❑ replicative senescence can be triggered by a DNA
damage response due to the shortening of telomeres.
Cells can also be induced to senesce by DNA damage in
response to elevated reactive oxygen species (ROS),
activation of oncogenes, and cell-cell fusion.
• CELLS FROM PATIENTS WITH
WERNER SYNDROME , A RARE
DISEASE CHARACTERIZED BY
PREMATURE AGING , HAVE A
MARKEDLY REDUCED IN VITRO
CELLULAR LIFE SPAN ( TISSUE
CULTURE ) , AS COMPARED TO
CELLS TAKEN FROM HEALTHY
CHILDREN WHICH HAVE THE
CAPACITY TO UNDERGO MORE
ROUNDS OF REPLICATIONS &
LONGER LIFE SPAN ALSO SEEN
IN PROGERIA SYNDROME .