CELL INJURY

B.M.C.Randika Wimalasiri
B.Sc in MLS(Peradeniya)
Lecturer(Probationary)
Department of Medical Laboratory Sciences
 Types/ Examples of Cell Injury

1. Hypoxic and Ischemic cell Injury

• When there is partial or total deprivation of
oxygen for tissues.
• Ischemia injures cells more than hypoxia.
 Hypoxia Ischemia
• any state where oxygen is • total stoppage of both
reduced. I.e. anemia, oxygen and nutrients
carbon monoxide
poisoning. • Due to
• Oxygen reaching to the – a mechanical
tissues is reduced obstruction (obstruction
• Essential amino acids, to an artery) -most
glucose and metabolites common
reach the tissues. – sudden loss of a lot of
• Mechanisms of non oxygen blood or
dependent (Anaerobic) – sudden reduction in
respiratory mechanisms blood pressure
synthesize a lesser amount • Anaerobic respiration
of ATP and help maintain too unavailable due to
basic cell function
unavailability of the
substrate Glucose
 Example & mechanism of
Ischemic injury
• Complete occlusion of an end artery of an
organ. i.e. blockage of a coronary artery by
atheroma causing myocardial damage.
• Up to a certain point in the occlusion, if blood
flow is re-established, the injury is reversed.
• If not progressive damage with further loss of
ATP till a point of no return is reached and
further damage is irreversible.
• One minute after coronary blockade
myocardium ceases to contract. This does not
mean that cell death has occurred. The death of
cardiac muscle cells takes up to 30 – 40
minutes.
2. Ischemia- reperfusion injury
• Tissues are damaged due to ischemia and if blood
flow is restored suddenly in the cells that are
reversibly injured, they recover completely.
• If they are irreversibly damaged no difference is
made with reperfusion (Restoration of blood flow).
• Reperfusion injury- more cells can die after
reperfusion of an ischemic tissue by necrosis or
apoptosis.
– due to formation of oxygen free radicals. These are
metabolites which form with the metabolites of cell injury
and the oxygen.
 1.6 Morphology of cell injury
• Cell injury- first biochemical changes and changes
at molecular level
• Morphological changes takes a longer time to
appear
• Evidence of ischemic cell injury and death:in
minutes or hours when using histochemistry and
ultrastructural examination
• Take hours or days for gross or light microscopic
morphological changes to manifest themselves.
• Morphological changes of reversible cell injury
occur earlier than those of irreversible injury.
• Example:Myocardial infarction due to
blockade of a coronary artery.
– Release of and leakage of cellular enzymes :
within 2 hours of the injury
– Irreversible damage to the myocardium :
Within 30 to 60 minutes
– Light microscopic changes of cell death :in 4
to 12 hours.
 1.6.1 Morphology of
reversible cell injury
1. Cell swelling
• The first morphologic
change
• Difficult to see in individual cells, easier to
realize in the whole organ.
• Make the organ large, increase its turgor
and its weight, appear pale.
2. Fatty Change
• Occurs as a result of hypoxic damage, chemical
and metabolic injury.
• Abnormal accumulations of triglycerides within
parenchymal cells.
• Manifested by the appearance of lipid vacuoles
in the cytoplasm.
• Occurs in cells involved in fat metabolism. I.e.
myocardial cells and liver cells.
• Morphologically small or large lipid vacuoles are
seen in the cytoplasm
 Cell death
• Impossible to determine the sequence of
damage because
– there are numerous causes of cell injury
– there are numerous mechanisms causing cell
damage
• There is no definite point for the point of
no return and therefore there is no final
common pathway by which cells die.
• However, there are two things consistently indicate
irreversibility.
1. mitochondrial damage even after the original injury is
resolved.
2. Severe membrane damage with profoundly compromised
function.
 The most important sites of membrane - mitochondrial
membrane, the plasma membrane, and membranes of
lysosomes.
 Damage to lysosomal membrane releases enzymes into the
cell and digests it. Enzymes are also released into the
extracellular space and digest the cells and tissues around it.
• Two principal types of cell death, necrosis and apoptosis
differ in their morphology, mechanisms, and roles in
physiology and disease.
 Definition
• Two principal types of cell death, necrosis and
apoptosis differ in their morphology,
mechanisms, and roles in physiology and
disease.
• Necrosis- a series of changes that accompany
cell death, largely resulting from the degradative
action of enzymes on lethally injured cells.
• Apoptosis- a pathway of cell death that is
induced by a tightly regulated suicide program in
which cells destined to die activate enzymes
capable of degrading the cells’ own nuclear DNA
and nuclear and cytoplasmic proteins.
 Necrosis Apoptosis
• Occurs when damage to • Occurs when the cell’s
membranes is severe, DNA or proteins are
lysosomal enzymes enter damaged in a way that it is
the cytoplasm and digest unable to repair, the cell
and degrade the cells. kills itself .
The cell and cellular
contents leak out. • Physiologic process -a
• Pathologic process. form of cell death
characterized by nuclear
dissolution, fragmentation
of the cell without complete
loss of membrane integrity,
and rapid removal of the
cellular debris.
• Serves many normal
functions and is not
necessarily associated with
cell injury.
 Morphology of irreversible
cell injury
• Irreversible cell injury -necrosis.
• Necrosis is the death of a group of cells occurring in
living tissue.
• Enzymes causing degradation may also come from
the white blood cells that migrate to the scene of cell
injury.
• The contents leaking out of these white cells may
cause inflammation of the surrounding tissues.
• These changes occur in hours and so in a case of
sudden death from a myocardial infarction where
there would be no detectable changes except a
blocked coronary artery.
 Morphological changes of
necrotic cells
1. Changes in Cytoplasm
• Extreme eosinophilia in hematoxylin and
eosin (H & E) stains – can be caused by. 2
reasons.
– Increased uptake of eosin pigment by damaged
cells due to increased binding to denatured
proteins
– RNA in the cytoplasm imparts basophilia. This is
lost when RNA is denatured
• Glassy homogenous cytoplasm – due to
loss of glycogen particles
• Vacuolation of the cytoplasm due to
digestion of organelles
• Myelin figure eventually replace the dead
cells. These are large whorled (i.e spiral)
phospholipid masses.
• Formation of fatty acids by degradation
products of myelin figures and calcification
of such fatty acids leading to generation of
calcium soaps
2. Changes in Nuclei - Three patterns are seen
• Pyknosis - Nuclear shrinkage and increased
basophilia. Chromatin condenses into a solid,
shrunken basophilic mass.
• Karyorrhexis - Pyknotic nucleus undergoes
fragmentation. The nucleus of the necrotic cell
totally disappears in a day or two.
• Karyolysis - A change that presumably reflects
loss of DNA because of enzymatic degradation
by endonucleases. Basophilia of the chromatin
may fade in this condition.
• Necrotic changes occur in individual necrotic
cells. When these changes are seen as a
whole several patterns are recognized. These
are;
1. Coagulative Necrosis –
• The primary change – denaturing of proteins.
• The basic outlines of the cells are preserved
at least for some days.
• Affected tissue is firm in texture. The necrotic
cells are later phagocytosed by scavenger
cells.
• Hypoxic cell death in all tissues except the
brain.
• Occurs as a result of infarcts.
2. Liquefactive necrosis –
• Prominent event is enzyme digestion
• Liquefaction completely digests the dead cells
and form a viscous liquid mass.
• In the cases of bacterial and fungal infections
inflammatory cells accumulation is increased
while increased release of enzymes of
inflammatory cells give rise to liquefaction .
• Hypoxic injury to the brain also results in this
pattern.
• In bacterial infections this mass is creamy and
yellow and is called pus.
Liquefactive necrosis - lung
abscess

http://kobiljak.msu.edu/cai/HM561_Pathology/Injury/Lab1-Image16.html
• Caseous necrosis - is a distinctive form
of coagulative necrosis seen in
tuberculosis. Microscopically it appears as
amorphous granular debris composed of
fragmented, coagulated cells within a
distinctive inflammatory border.
• This is called a granulomatous reaction.
• Caseous’ indicates the cheese-like
appearance of the tissue surrounded by
the immune cells.
http://dc433.4shared.com/doc/Js40CYQJ/preview.ht
ml
• Fat necrosis - describes focal areas of fat
destruction. Ex:chronic pancreatitis.
• Pancreas- produce digestive enzymes which help
us to break down the food that we have eaten: they
are passed to the small intestine through the
common bile duct.
• If this duct is blocked (usually by a gallstone), the
enzymes then turn against the pancreas and result
in acute pancreatitis: essentially, the pancreas
starts digesting itself!
• Identification
– naked eye: fat saponification (chalky
white areas (Fatty acids combine with
calcium salts) that develop as a result of
fat breaking down into fatty acids)
– Microscope: fat (clear) cells with calcium
deposits that appear bluish and the
presence of inflammation
• In this condition pancreatic enzymes leak out of
acinar cells and liquefy the membranes of fat
cells in the peritoneum.
• Enzymatic digestion of the pancreas take place.
• Fatty acids released and combine with calcium
salts to produce chalky white areas on gross
inspection.
• Microscopically there are shadowy outlines of
necrotic fat cells, with inflammation and calcium
deposition.
• http://www.weallhaveuniquebrains.com/wp-
content/uploads/2014/01/fat-necrosis.jpg
• Mitochondria are swollen
due to loss of volume
control; membranes from
disrupted mitochondria form
“myelin figures” such as the
one shown here. These are
stacks of laminated figures
in the form of spheres in the
injured cytoplasm. (Despite
the name, they are not
"myelin" and are not
comparble to the myelin
sheath of axons.)
 Apoptosis

• Apoptosis is programmed cell death.

• Although it can happen in certain pathologic
conditions, apoptosis is the process by which
elimination of cells take place in physiological
events.
• Important in the regulation of normal cell
populations.
• An example is cell deletions in proliferating
epithelial populations, parenchyma organs,
endometrial cells, hormone dependent cells,
immune cells.
• Apoptotic cell death also takes place in tumours,
viral diseases and treatment with anti-cancer
 Morphology
of apoptosis
• Cells are single or in small clusters
• Cell shrinkage-Cells are smaller in size than the
surrounding viable cells due to cell shrinkage.
• The cytoplasm is dense and eosinophilic due to
tightly packed organelles.
• Chromatin condensation- This is the most
characteristic feature of apoptosis. Chromatin is
condensed near nuclear margins. Nucleus is dense
and fragmented.
• Unlike necrosis apoptosis does not elicit an
inflammatory response.
• Apoptosis is generally lasts a lifetime and be
beneficial for the body.
REFERENCES

(1)Kumar, Abbas, Fausto. Robbins and

Cotran, Pathologic Basis of Disease 7 th
Edition(2004) Elsevier Inc. Cellular
Responses to Stress and
Toxic Insults: Adaptation, Injury, and
Death: Chapter 1 pg.3-20.

(2)http://classes.midlandstech.edu/carterp/c
ourses/bio225/chap04/lecture6.htm
(3)http://www.lhsc.on.ca/Patients_Families_
Visitors/CCTC/Words/ischemia.htm
(4) http://www.newhealthguide.org/Types-
Of-Bacteria.html
(5)
http://www.bioquellus.com/technology/micr
obiology/influenza-virus/
(6)
http://www.sophia.org/concepts/cytoskelet
on
Thank You!!!!