Cell injury notes

1. Necrotic leg wound caused by a
brown recluse spider bite

2. IRREVERSIBLE CELL INJURY
Necrosis
NECROSIS
Definition:
Necrosis Necrosis ("death, the stage of dying, the act of
killing") is the premature death of cells in living tissue.
Necrosis is caused by factors external to the cell or tissue,
such as infection, toxins, or trauma.
This is in contrast to Apoptosis, which is a naturally
occurring cause of cellular death.
While apoptosis often provides beneficial effects to the
organism, necrosis is almost always detrimental and can be
fatal.

3. Causes of cell necrosis: See before, but
the most common causes of cell death are
viruses, ischaemia, bacterial toxins,
hypersensitivity, and ionizing
radiation.
Morphologic change in necrosis:
The changes don’t appear in the affected
cells by light microscopy before 2-6 hours
according to the type of the affected
tissue.

4. Chang e s in the cyto plasm :
i. Swelling and granularity of the
cytoplasm due to (a) Imbibition of
water (↓ATP in the cell) (b)
Coagulation of the cytoplasm.
ii. Loss of cellular membrane and
release of intracellular enzymes in
the blood e.g. Serum
Transaminase(ST )& LDH where
their detection is of diagnostic
value in liver and heart diseases.
iii. Fusion of cells forming
homogeneous eosinophilic mass.

6. N ar chang e s:
ucle
Occur due to hydrolysis of nucleoproteins:
i. Pyknosis i.e. the nucleus becomes shrunken
condensed and deeply stained.
ii. Karyorrhexis: rupture of nuclear membrane
with fragmentation of the nucleus.
iii. Karyolysis: the nucleus dissolves and
disappears.
Finally the affected tissue changes to
homogeneous eosinophilic mass with
nuclear debris.

7. NUCLEAR CHANGES IN NECROSIS

8. Ty of necrosis
pes
The variable types of necrosis differ as
regards causes, gross and microscopic
pictures.
(1) Coagulative necrosis:
It is mainly caused by sudden ischaemia e.g. infarction
of heart, kidney and spleen. The protein of the
affected tissue becomes denaturated.
Grossly, it appears dry pale opaque. It is triangular ?
subcapsular with the base towards the capsule of the
affected organ. This is due to the fan like
distribution of the supplying blood vessels. The
infarct area is surrounded by narrow zone of
inflammation and congestion.
Microscopically, the structural outline of the
affected tissue is preserved but the cellular details
are lost.

9. GROSS AND MICROSCOPIC PICTURE OF NECROSIS

10. (2) Liquifactive necrosis
The necrosed tissue undergoes rapid softening
e.g. infarction of the nervous tissue which
has abundant lysosomal enzymes. Also, this
type of necrosis occurs in case of suppurative
inflammation (Abscess) where liquefaction
occurs under the effect of proteolytic enzymes
of PNLs liquefaction of the amoebic abscess
occurs due to the effect of strong proteolytic
enzymes and hyaluronidase secreted by E.
Histolytica.
Grossly: the affected tissue appears as
homogenous amorphous substance.
Microscopically: it appears as homogenous
eosinophilic structure.

12. (3) Caseous necrosis:
• It is characteristic of tuberculosis. The
necrotic tissue undergoes slow partial
liquefaction forming yellow cheesy material.
• Microscopically, it shows amorphous granular
eosinophilic material lacking the cell outlines.
• Unlike coagulative necrosis, the necrotic cells
do not retain their cellular outlines, and do
not disappear by lysis, as in liquifactive
necrosi
• Grossly, the caseous material resembles
clumpy cheese, hence the name caseous
necrosis.
• The cause of necrosis in TB is hypersensitivity
reaction caused by the tuberculoprotein

13. Caseous necrosis in LN.
Amorphous ,granular ,eosinophilic ,necrotic center is surrounded by
granulomatous inflammation.

14. T.B LUNG :
(Large Area Of Caseous Necrosis) AREA ,YELLOW-WHITE
AND CHESSY

15. (4) Fat ne cro sis
it is necrosis of adipose tissue
including two types:
a) Traumatic: caused by trauma to
adipose tissue e.g. breast and
subcutaneous tissue.
b) Enzymatic: which occurs in case of
acute haemorrhagic pancreatitis.
Obstruction of the pancreatic duct
leads to release of lipase which
splits the fat cells of the omentum
into fatty acid (combine with Ca
giving chalky white calcification)
and to glycerol which is absorbed
in the circulation.

16. (5) Fibrino id ne cro sis
This is characterized by swelling,
fragmentation, increased eosinophilia of
collagen fibers and accumulation of
mucopolysaccharides and fibrin due to
vascular exudation of fibrinogen at the
site of lesion, e.g.:
a) Collagen diseases (Rheumatic fever,
Rheumatoid, Sclerodermia, Lupus
erythematosus and Polyarteritis
nodosa).
b) In the wall of blood vessels in
malignant hypertension

17. FIBRINOID NECROSIS

18. (6 ) Ze nke r’s ne cro sis:
Of the rectus abdominus muscle and
diaphragm as a complication of :
bacterial infection particularly typhoid
fever.
The striated muscles lose its
striation, swell and fuse together in
homogeneous structureless mass.

19. (7 ) Gang re no us ne cro sis:
The tissue in this case have undergone
ischaemic cell death and coagulative
necrosis followed by liquifactive action of
putrefactive organisms. When
coagulative pattern is dominant the
process is termed dry gangrene.
When the liquifactive action of the
bacteria
is more pronounced it is called wet
gangrene.

20. Obtraction of the bloodsupplytoto bowelis almost followed by
Obstruction of blood supply the bowel is alrmost followed by
gangrene.
Gangrene

21. Fate and local effects OF NECROSIS :
1. A small area undergoes repair:
A) The products of the necrotic cells irritate the
surrounding tissue forming a zone of
inflammation.
B) The accumulated neutrophils in the zone of
inflammation soften the necrotic tissue and
make its removal by macrophages and blood
stream easy and help the process of healing.
C) Repair by regeneration or fibrosis depends
upon the type of cells affected (labile-stable-
permanent).

22. 2. If the necrotic area is wide, its
products can’t be removed and a fibrous
capsule form around it in order to
separate it from the living tissue. Areas
of necrotic softening in the brain become
surrounded by proliferated neuroglia
(gliosis).
3. Old unabsorbed caseous lesions and
fat necrosis usually becomes heavily
calcified (dystrophic calcification).
4-when the necrotic tissue is infected with
putrefactive Organism------Gangrine

23. General effects of necrosis
1. Release of enzymes from the
breakdown tissue into the blood
forms the basis of clinical tests for
diagnosis e.g. detection of
transamenase in myocardial
infarction and liver necrosis in
hepatitis.
2. Absorption of dead products into

25. N.B.:
I. Necrosis of:
1) Of small groups of cells is called focal
necrosis.
2) Of large groups of cells is called confluent
necrosis.
3) Of extensive areas of an organ is called
massive necrosis.
II. Somatic death means death of the individual.
III. Post-mortum autolysis of the tissue
occurring after death can be differentiated
from necrosis by the absence of inflammatory
zone around the affected tissue (inflammation

26. A pto sis
po
Definition:
• It is programmed death of cells in living tissues.
It is an active process differing from necrosis by
the following points:
• Occurs in both physiological and pathological
conditions.
• Starts by nuclear changes in the form of
chromatin condensation and fragmentation
followed by cytoplasmic budding and then
phagocytosis of the extruded apoptotic bodies.
• Plasma membrane are thought to remain
intact during apoptosis until the last stage so
does not initiate inflammatory reaction around
it.

28. Death by Committing Suicide
AP T
OP OSIS
While committing
suicide cells:
 Shrink
 Chromatin Degraded
 Mitochondria Break
Down
 Break into
Membrane-bound
Fragments
 Phosphatidylserine
Exposed
 Phagocytic Receptors

29. Microscopically:
In the tissue stained with H & E
apoptosis affects single or small
clusters of cells and apoptotic cell
appears as round mass of intensely
eosinophilic cytoplasm with dense
nuclear chromatin fragments.

30. Major criteria of Apoptosis
1- Morphological changes
2- Chromatin condensation
3- DNA fargmentation
4- Cell death

32. Initiation for apoptosis
Factors predisposes to apoptosis
1- Nontoxic stimuli can lead to apoptosis .
2- loss of growth factors.
3- Direct action of cytokines (e.g., tumor
necrosis factor)
4- Immune system action (e.g., natural killer
cells or cytotoxic T lymphocytes).
5- Viral infection.
6- Adult tissue homeostasis .
7- Sublethal damage to the cells (e.g., by ionizing
radiation, hyperthermia, toxins.)
8- Loss of cell-cell or cell-matrix attachments.

33. Examples of physiologic and pathologic cases
accompanied with apoptosis:
1. Programmed cell death during
embryogenesis.
2. Hormone dependent cell involution in case
of endometrial cell break down during
menstrual cycle.
3. Cell death in tumours during regression
induced by cytotoxic drugs or irradiation.
4. In some viral disease e.g. viral hepatitis in
which apoptotic cells are known as
councilman bodies.

34. ROL (VAL )OF AP T
E UE OP OSIS
1-Defense:
Against nonself multicellular organisms (cell
commits suicide when infected by a virus may
protect other cells from further spread of the
virus)
2-Digestion:
The cellular DNA destroy the genetic
information of any external stimulus.
3-Protecting:
Protection of the organism from unregulated

35. Apoptosis vs. Necrosis
Apoptosis Necrosis
• Cells shrink and condense • Cells swell and burst,
• Release small membrane releasing their intracellular
bound bodies contents
• Small fragments are • Damaging to surrounding
engulfed by surrounding cells
cells • Causes inflammation

36. RE RSIB E CE L INJ
VE L L URY
Hydropic swelling
Hydropic swelling is an acute stress cell injury
caused by a variety of agents leading to swelling
in the cells.
Pathogenesis:
Hydropic swelling results from impairment of the
process controlling ionic sodium concentration
in the cytoplasm. This regulation is controlled
by: (i) Plasma membrane itself, (ii) Plasma
membrane sodium pump, (iii) The supply of
ATP.
Injurious agents may interfere with one of these
factors leading to intracellular accumulation of
sodium and increase water to maintain
isosmotic condition of the cell. The result is

37. Structural changes:
Grossly, the affected organ increases in
size becomes pale, bloodless, having
sharp edge which bulge over the capsule
on cut section of that organ.
Microscopically, the cell becomes large
with pale cytoplasm and normally
located nucleus.
Examples of hydropic swelling:Ballooning of hepatocytes
in cases of acute viral hepatitis, epidermal cells in burns,
Mickulicz cell(Histiocytes) in Rhinoscleroma .

39. Viral hepatitis
The hepatocytes
adjacent to the
portal tract (right)
are very swollen
and hydropic
(severe ballooning
degeneration)

40. CE L AR ADAP AT
L UL T ION
DIFINITION:
Cellular adaptation is a state that lies
intermediate between the normal unstressed
cell and the injured over stressed cells.
The major most important adaptive changes in the
cells are: Hyperplasia, Hypertrophy, Atrophy,
Metaplasia, Dysplasia and intracellular storage.

41. Hyperplasia:
Definition:
It is an increase in the size of tissue or organ
due to increase in the number of its
specialized cells. This can result from:
1. Increased functional demand:
• Physiological hyperplasia of the breast in
pregnancy and lactation.
• Hyperplasia of the bone marrow in haemolytic
anaemia, Fe, B12 or folic acid deficiency
anaemias.
• Hyperplasia of the lining epithelia in the
process of regeneration and repair of an ulcer

42. 2. Increased hormonal stimulation
A) Hyperplasia of endocrine glands:
* Pituitary gland → excess growth
hormone:
• Before puberty → gigantism.
• After puberty → acromegaly.
* Thyroid gland → thyrtoxicosis. *
Parathyroid gland → hypercalcaemia →
metastatic calcification → osteitis
fibrosa cystica.
* Adrenal cortex → Cushing’s
syndrome.

43. THYROID
HYPERFUNCTION
Exophthalmos

44. B) Hyperplasia of endocrine-target
organs:
*Breast → mammary cystic hyperplasia
(Fibrocystic disease).
* Endometrium → endometrial hyperplasia.
* Prostate → senile nodular hyperplasia.
They result from increased oestrogenic stimulation.

45. ENDOMETRIAL HYPERPLASIA

46. Hyperplasia of Endocrine target organes
HYPERPLASIA OF ENDOCRIN TARGET ORGAN

47. 3. Chronic inflammation or irritation
Pressure from ill fitting shoes
causes hyperplasia of the skin
(calluses).
Chronic cystitis of the bladder
commonly causes hyperplasia of
the bladder epithelium
(Bilharziasis & stones).
Chronic inflammatory lesions
of the skin → hyperplasia.

48. 4. Hyperplasia of connective tissue
cells in wound healing (proliferating
fibroblasts and blood vessels.
5. Compensatory hyperplasia in the
liver after partial hepatectomy.

49. 6. Pseudoneoplastic hyperplasia:
a) Pseudomalignant connective tissue hyperplasia
e.g. pseudolymphoma of the orbit and
pseudosarcoma in fibrous tissue.
b) Pseudomalignant epithelial hyperplasia e.g.
keratoacanthoma and hyperplasia of the skin
around chronic ulcer.
Cell proliferation depends on the
action of:
a) Some growth factors and cytokines e.g.
epidermal growth factor (EGF)-alfa transforming
growth factor (TGF-α), Her- 2 neu-and
interleukin-6 (IL-6) and tumour necrosis factor
(TNF-α).

50. It Differs From Neoplasia
By The Following :
It occurs in tissue made up of labile or stable
cells that have the power of regeneration
under normal or pathologic conditions.
Occurs in response to a stimulus, continues
as the stimulus continues and disappears
when it is removed.
Usually performs a function e.g. Lactating
breast.
It is a reversible non-neoplastic process,
nevertheless sometimes malignant tumours do
arise on top of abnormal or atypical
hyperplasia (Endometrial hypeplasia).

51. HY ERTROP
P HY
DIFINITION:
It is the increase in the size of the organ
or
tissue due to increase in the size of it
specialized cells
In a pure form, it is found in muscles:
1. Occurs in response to an increased
demand for overwork:
a) Skeletal muscle in athelets

52. Smooth muscles
The uterus in pregnancy.
Stomach in pyloric stenosis.
Alimentary tract proximal to an
obstruction.
Urinary bladder with obstruction to
urine outflow e.g. prostatic
enlargement or urethral stricture.

53. With hypertrophy of the muscle wall

54. c) Cardiac muscle:
* Right ventricle: in MS, Tl, PS,
chronic lung diseases.
* Left ventricle in MI, AS, AI,
systemic hypertension.

55. Chronic lung diseases:
RS Hypertrophy
MS
MI
RSH hypertrophy
LS Hypertrophy

57. • 2. Physiologic (hormonal)
hypertrophy: occurs during
maturation under the effects of
hormones. Sex hormones at puterty
lead to hypertrophy of juvenile sex
organs, and breast tissue in
lactating women under the effect of
prolactin.
• 3. Compensatory hypertrophy of
one kidney due to removal of the
other

58. Blood supply Nerve Supply
Hormonal Stimulation Does A Function

59. Mechanisms include:
1. Loss of innervation.
2. Reduced nutrient and oxygen supply.
3. Reduced functional demand.
4. Reduced hormonal stimulation.
These can occur under
physiologic or pathologic
conditions.

60. A) Physiological atrophy
Ductus arteriosus and umbilical
vessels,after birth.
Thymus gland after puberty.
Lymphoid tissue in adenoid and
tonsils.
Postmenopausal atrophy of the
breast, uterus and ovaries.
Aging process in the skin, brown
atrophy of the heart and brain
atrophy.

61. B) Pathologic atrophy:
1. Ischaemic atrophy: usually due to partial and
gradual occlusion of the arterial blood supply by
atherosclerosis, in the heart (atherosclerotic heart
disease), brain or kidney etc.
2. Disuse atrophy: due to forced inactivity of muscle
e.g. after
prolonged immobilization of a limb in plaster (Cast).
3. Neuropathic atrophy: following lower motor neuron
lesions e.g. poliomyelitis.
4. Pressure atrophy upon a localized area or group of
cells, interfering with its blood and nutrient supply.
* Pressure by growing tumour.
* Prolonged pressure of a pulsating aortic aneurysm
may cause pressure atrophy of the undersurface of the
sternum anteriorly or of the bodies of the vertebrae

62. Gradualsupply & cellular in supply supply nutrients lead to Reduction in
Grodual diminution in blood
oxygen diminution atrophy; blood a nd
and nutrients
Lead to reduction in oxygen supply &cellular atrophy
Normal Accumulation 0 f lipofucsin around nucleus

63. Preasure Atrophy on renal tissue by distended pelvis
Increasing
/ pressure
Pelvis greatly
distended
Obstruction incomplete

64. Hormonal atrophy: cessation of
pituitary activity results in atrophic
changes in the thyroid, adrenals,
ovaries and other organs that are
influenced by pituitary hormones.
Secondary to immunologic injuries:
the resulting tissue damage is
accompanied by fibrosis and
atrophy of the affected organ e.g.
primary Addison’s disease due to
autoimmune bilateral atrophy of
adrenal gland, atrophic gastritis,
atrophic thyroiditis, testicular

65. METAPLASIA
Definition :
It is the transformation of one type of
differentiated tissue into another type of the
same kind. It may occur in either epithelial
or connective tissue. Pathogenesis:
Metaplasia is thought to arise from
reprogramming of stem cells to differentiate
along new pathway under the effects of
mixture of cytokines and growth factors.
The most common is the replacement of a
glandular epithelium by a squamous one due
to prolonged chronic irritation, replacing the
thin delicate epithelium with the tougher and
more resistant squamous epithelium.

67. A) Epitlielium metaplasia
1. Squamous metaplasia: 2. Columnar metaplasia
( 1) Squamous metaplasia
a) From pseudo-stratified columnar:
* Trachea and bronchi in chronic bronchitis, cigarette smoking
and bronchiectesis.
* Nasal sinuses in chronic sinusitis and hypovitaminosis A.
B) From transitional epithelium in bilharziasis of U.B.
c) From simple columnar epithelium:
* Endocervical mucosa and glands in cervical erosion.
* Gall bladder with stones.
d) From mesothelium of the pleura and peritoneum.

68. (2) Columnar metaplasia
(A) From squamous: in the lower oesophagus
e.g. Barrett oesophagitis (Precancerus).
(B) Intestinal metaplasia of the specialized
gastric mucosa in chronic atrophic gastritis.
(C) Apocrine, pink cell, hyperplasia seen in
fibrocystic disease of the breast.
(D) In mesothelium of pleura, peritoneum and
synovium.

70. (B) Connective tissue metaplasia
• - It is the formation of cartilage, bone or
adipose tissue, in tissues that normally
do not contain these elements.
• Osseous metaplasia: occurs in:
(a) Sites of dystrophic calcification e.g. in
scars, old T.B.
(b) In muscles, in post-traumatic myositis
ossificans.

71. Formation of bone in fibrous tissue
In case of healing of a wound
Scar
Bone

72. Dysplasia
(Intraepithelial neoplasia)
Definition: It is partial loss of differentiation.
1. The involved epithelium shows evidence of
cellular atypia:
Pleomorphism of cells (variation in size and
shape).
Hyperchromatic nuclei with increased nucleo-
cytoplasmic ratio and increased mitotic activity.
Loss of polarity (orientation) of cells.
Disordered maturation with impaired function.
No invasion of basement membrane.
2. It represents reaction to underlying
inflammation or to chronic irritation.
3. Mild and moderate degrees of dysplasia are

74. Carcinoma in situ.
A section of the uterine cervix shows neoplastic
squamous cells occupying the full thickness of the
epithelium and confined to the mucosa by the underlying
basement membrane.

75. 4. Examples of dysplasia:
• 1. Occurs in the cervix in chronic cervicitis.
• 2. In urothelium of urinary bladder in case
of bilharziasis.
5. The most severe form, when the changes
occupy the whole thickness of the
epithelium indicates the diagnosis of
intraepithelial carcinoma or carcinoma in
situ (pre-invasive carcinoma). Carcinoma in
situ characterized by diffuse cellular atypia
involving the whole thickness of the
affected epithelium without invasion of the
basement membrane. The commonest sites
of IEN are cervix uetri, bronchial
epithelium, buccal mucosa and skin.