3.CELLULAR ADAPTATION, INJURY and DEATH 2012.ppt

Notes

1. CELLULAR ADAPTATION, INJURY and
DEATH
Introduction
•Whenconfrontedwithstressesthatendanger
itsnormalstructureandfunction,thecell
undergoesadaptivechangesthatpermit
survivalandmaintenanceoffunction

2. Introduction
•reactions of cells and tissues to injurious agents,
including genetic defects, is key for the
understanding of disease processes.
•cellular changes can occur due to the
-adaptation,
-injury,
-neoplasia,
-aging
-death.

3. Cellular Adaptation
•Cellularadaptationisastatethatliesintermediatebetween
thenormal,unstressedcellandtheinjured,over-stressed
cells.
•Cellsmustconstantlyadapt,evenundernormal
conditions,tochangesintheirenvironment.
•Somewhatmoreexcessivephysiologicstressor
somepathologicstimulicanbringaboutanumberof
physiologicandmorphologicchangesinwhichanewbut
alteredsteadystateisachieved,preservingtheviabilityofthe
cells-calledcellularadaptation.

4. Cell Injury
•If the limit of adaptive response to a stimulus is exceeded, or in certain
instances when adaptation is not possible, a sequence of events follows,
termed as cell injury.
•Cell injury is reversible up to a certain point but if the stimulus persists or
severe enough from the beginning, the cell reaches the point of no return
and suffers irreversible cell injuryand cell death.Cell death is the ultimate
result of cell injury.
•Reversible cell injury, irreversible cell injury, necrosis and apoptosis are
morphologic patterns of acute cell injury.
•There are other patterns of morphologic alteration, such as subcellular
alteration, which occur largely as a response to more chronic or persistent
injurious stimuli;
–intracellular accumulation, which occur as a result of derangement in the
metabolism or excessive storage;
–pathologic calcification, an accumulation of Calcium in the cell -a
common consequence of cell and tissue injury.

5. Cellular responses to injurious
stimuli
1. Cellular Adaptation
–Atrophy
–Hypertrophy
–Hyperplasia
–Metaplasia
2. Acute cell injury
Reversible cell injury
•Cellular swelling
•Fatty change
Cell death
•Necrosis
•Apoptosis
3. Intracellular accumulation
• Pathologic calcification.
• Sub-cellular Alteration and cell
inclusions

6. Types of Cellular Adaptation
•Physiologic Adaptation
–Usuallyrepresentsresponsesofthecellstonormalstimulation
byhormonesorendogenouschemicalsubstances,e.g.
enlargementofbreastandinductionoflactationby
pregnancy.
•Pathologic Adaptation
–Maysharethesameunderlyingmechanism,buttheyprovide
thecellswithabilitytosurviveintheirenvironmentand
perhapsescapeinjury.

7. General Mechanism of Cellular
Adaptation
• Up-or down-regulation of specific cellular receptors involved in metabolism
of certain components, e.g. in the regulation of cell surface receptors
involved in the uptake and degradation of low-density lipoproteins (LDL).
•Induction of new protein synthesis by the target cells, e.g. heat-shock
response.
•Production of one type a family of proteins to another or markedly
overproducing one protein e.g. cells producing various types of collagens
and ECM proteins in chronic inflammation and fibrosis.

8. Adaptationinvolvesallstepsofcellular
metabolismofproteins–receptorbinding,signal
transduction,transcriptionorregulationof
proteinpackagingandrelease.

9. •Different types of cellular injuries
-hypoxic (lack of sufficient oxygen),
-free radical
-infectious.
These types of injuries can have different clinical and
pathologic manifestation. When cells of a living
human organism are exposed to a noxious(physically
harmful)agents, they become injured.

11. Cellular Reaction Pattern To Stress
Depends On:
1.Type, duration, and severity of stress.
2.Type, state and adaptability of cell.
I-Irreversible Cell Injury:
Severe stimuli leads tonecrosis.& Apoptosis
II-Reversible Cell Injury:
Mild stress for short duration leads to biochemical change or
mild form of morphologic change in the affected cells
( hydropic swelling).

12. Cellular adaptation
•When cells of a living human organism are
exposed to a noxious agent, they become
injured.
•They are four ways of respond
-get bigger,
-get smaller,
-proliferateor
-die.

13. Persistent prelethal stress
leads to cellular adaptation.
1-Adaptation of growth.
a) Increased growthand cellular activity e. g. Hypertrophy &Hyperplasia
b) Decreased growth and cellular activity e.g. Atrophy.
2-Disturbances of cellular differentiation and
morphologye.g.Metaplasia,& Dysplasia.

14. Persistent prelethal stress
leads to cellular adaptation.
.
3-Intra and Extra cellular accumulations
e. g.
Lipidsas infatty change& Cholesterol deposits.
Proteinsas inHyaline change& Amyloidosis.
Pigmentsas inPathologic pigmentation.
Calciumas inPathologic Calcification
Enzymatic metabolic deficiencyasin Gout& lyzosomal storage
disease.

15. Cellular adaptation …
•Cells adapt to their environment to escape
and protect themselves from injury.
•An adapted cell is neither normal nor injured.
•In many disease conditions, cellular
adaptation are common.. The most significant
adaptive changes in cells are;

16. Cellular adaptation …
The most significant adaptive changes in cells
are;
•atrophy-decrease in cell size
•hypertrophy–increase in cell size
•hyperplasia–increase in cell number, and

17. Cellular adaptation …
•dysplasia–deranged cellular growth which is
an atypical hyperplasiaand can not be
considered as true cellular adaptation.
•metaplasia–reversible replacement of one
mature cell type by another, less mature cell
type

18. Terminology:
•Necrosis:Morphologic changes seen in dead
cells within living tissue.
•Autolysis:Dissolution of dead cells by the cells
own digestive enzymes.
•Apoptosis:Programmed cell death.
Physiological, for cell regulation.

19. Atrophy
Is a decrease or shrinkage in cellular size
•it can affect any organ,
•but it is most common in skeletal muscle, the
heart, secondary sex organs and the brain.

20. Atrophy…
The cause of atrophy can be decreases in;
•workload
•use
•blood supply
•nutrition
•hormonal stimulation and
•nervous stimulation

21. Atrophy…
•when individual immobilized in bed for prolonged
time exhibit a type of skeletal muscle atrophy called
disuse atrophy.
•in aging individuals brain cells become atrophic due
to decrease of blood supply.
•gonads to shrink due to decrease in hormonal
stimulation.
All atrophic cells exhibit the same basic changes.

22. Cerebral atrophy -Alzheimer's:

23. Muscle ischemic atrophy:

24. Hypertrophy
Is an increase in the size of cells and
consequently in size of the affected organ
•increasedincellularsizeisassociatedwithan
increasedaccumulationofproteininthe
cellularcomponentsandnotwithanincrease
incellularfluid

25. Hypertrophy…
•Anexampleofnormalorphysiologichypertrophyis
theincreasedgrowthoftheuterusandmammary
glandsinresponsetopregnancy.
•Pathologichypertrophyoccursastheresultof
diseaseconditions.
•maybeadaptiveorcompensatory.
•thethickeningoftheurinarybladderandmyocardial
hypertrophyareexampleofpathologicalhypertrophy

26. Hyperplasia
•is an increase in the number of cells resulting
from an increased rate of cellular division.
•response to injury.
•can either be compensatoryor hormonalbut
often, the cause for hyperplasia is hormonal
stimulation..

27. Hyperplasia…
•Compensatory hyperplasia is an adaptive
mechanism to regenerate
-if the part of the liver is removed, the remain
liver cells (hepatocytes) will regenerate to
compensate
-70%of the liver regeneration can be
completed within 2 weeks
-is enhanced by HGFwhich acts as mediator
of liver regeneration.

28. Hyperplasia…
•Hormonal hyperplasia occurs chiefly in
estrogen-dependent organs, such as the
uterus and breast.
•Pathologic hyperplasiais the abnormal
proliferation of normal cells e.g. pathologic
endometrial hyperplasia.

29. Pathologic Hyperplasia
Most forms of pathologic hyperplasia are
instances of excessive hormonal stimulation or
are effects of growth factors on target cells,–
e.g.
hyperplasia of endometrium,
hyperplasia of prostate,
hyperplasia of connective tissue cells in wound healing,
skin warts.

30. Dysplasia
Abnormal changes in size,shapeand
organizationof mature cells
•it is not a true adaptive process but rather
called atypical hyperplasia
•it can be classified as mild, moderateor severe
•is a strong predictor of breast cancer
development.

31. Metaplasia
Is the reversible replacement of one mature cell type
by another.
–the replacement of normal columnar ciliated epithelial
cells by stratified squamous epithelial in bronchial.
–bronchial metaplasia can be reversed by the removal of
the stimulus.
–With prolonged exposure to the stimulus however,
cancerous transformation can occur.

32. (A)Epithelium metaplasia
1.Squamous metaplasia: 2.Columnar
metaplasia
( 1) Squamous metaplasia
a)From pseudo-stratifiedcolumnar:
* Trachea and bronchi in chronic bronchitis, cigarette smoking
and bronchiectesis.
* Nasal sinuses in chronic sinusitis and hypovitaminosisA.
b)From transitional epithelium in bilharziasisof U.B.
c)Fromsimplecolumnar epithelium:
* Endocervicalmucosa and glands in cervical erosion.
* Gall bladder with stones.
d)From mesotheliumof the pleura and peritoneum.

33. 2.Columnar metaplasia
From squamous:in the lower oesophagus e.g. Barrett
oesophagitis (Precancerous).
Intestinal metaplasiaof the specialized gastric
mucosa in chronic atrophic gastritis.
Apocrine,pink cell, hyperplasia seen in fibrocystic
disease of the breast.
In mesotheliumof pleura, peritoneum and synovium.

35. (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:
Sites of dystrophic calcificatione.g. in scars, old
T.B.
In muscles, in post-traumatic myositisossificans.

36. Enzymes increased
mechanism
It is an adaptive change that occurs in the cells
•by inactivating or detoxifying drugs or
chemicals by means of the enzymes present in
the SER.

37. Extracellular and intracellular
accumulations
Itoccurswhenthecellinjuryissublethalandsustained,
aswellasinnormalcells.
•electrolytes,triglycerides(lipids),glycogen,calcium,
uricacid,proteins,melaninandbilirubinare
commonaccumulations.
•Abnormalaccumulationsoccurwhenasubstanceis
producedataratethatexceedsitsmetabolismor
removal.

38. Accumulations
•Substancescanbeeither;
•normalbodysubstancesinabnormallylarge
amounts
-lipids,proteins,carbohydrates,melaninand
bilirubin
•abnormalendogenousproductsor
•exogenousproductsfromtheenvironment
andpigments

39. Intracellular
Accumulations
•Proteins
•Lipids (TG and Cholesterol)
•Pigments
•Glycogen (genetic disease)

40. Accumulations…
Causes of intracellular accumulation can be
•production of substances that exceeds the
metabolism
•genetic disorders,.
-in von Gierke's disease -deficiency of the enzyme
glucose-6-phosphatase
-in Tay-Sachs disease -abnormal lipids accumulation
in the brain and other tissues,

41. Accumulations…
Causes of intracellular accumulation can be
•cellular injuries of different level and causes
•over production of different pigments e.g. (Bilirubin,
Lipofuscin, melanin etc)
-Pigments can be endogenous or exogenous-
•accumulationfrom outside e.g. carbon, lead etc

42. Cellular Accumulations
Endogenous
Fat
Protein
Glycogen
Pigments & Other
Lipofuscin
Melanin
Hemosiderin
Uric Acid
Bacteria/virus
Exogenous
Carbon
(Anthracotic)
Tattoo

43. Pathologic calcification
It is the abnormal tissue deposition of calcium
salts;
•Dystrophic -occurs in dead or dying tissue
•Metastatic -occurs in normal tissue

44. CELL INJURY AND ADAPTATION
Thebasisofalldiseasesisinjurytothe
smallestlivingunitofthebody,namelythe
cell.
Cellencountersmanystressesasaresultof
changesintheirinternalandexternal
environments.
However,thenormalcellisinsteadystate
abletohandlephysiologicdemandaccording
toitsadaptivecapacity.

45. CELL INJURY AND ADAPTATION
Causes of cell injury:
1.Hypoxia(deficiency of oxygen) due to:
Ischaemia
decrease of oxygen carrying capacity of blood due to anaemia
cardiac or respiratory failure and
CO poisoning.
2. Physical agent:burns, deep cold, radiation, mechanical trauma and
electric shock.
3. Biological agentse.g. viruses, bacterial toxins, fungi and parasites.
4. Chemical agentsand drugs e.g. alkalis, acids, insecticides, alcohol and
narcotic drugs & air pollutants et..

46. CELL INJURY AND ADAPTATION
Causes of cell injury:
5. Endogenous toxinsas in case of uremia, jaundice and diabetic
ketosis.
6. Immunologic reactions(hypersensitivity).
7. Nutritional imbalancesuch as protein calorie malnutrition,
starvation, obesity, diabetes mellitus and deficiency of other
substances and vitamins.
8. Genetic abnormalitiesas in Down syndrome & sickle cell
anemia.

47. Cellular Injury
The ways of which cells are injured are grouped into five
categories;
–physical injury
–chemical injury
–biologic agents injury
–nutritional imbalances injury
–radiation injury

48. Cellular Injury
•most diseases begin with cell injury.
•cell injury can either be reversibleorirreversible.
•causes of both types of injury are similar
•many of the causes can result initially in reversible
injury.

49. Reversible vs. irreversible
cell injury
Reversible injury
* Decreased ATP levels
* Ion imbalance
*Swelling
•Decreased pH
•Fatty change (liver)
Irreversible injury
* Amorphous densitiesin
mitochondria
* Severe membrane damage
* Lysosomal rupture
•Extensive DNA damage

50. Cellular Injury
Early changes
•these are reversible and include:
-cytoplasmic swelling and vacuolation
-mitochondrial and endoplasmic reticulum
swelling
-clumping of nuclear chromatin.

51. Cellular Injury…
Late changes
•These are irreversible and include:
•densities in mitochondrial matrix
•cell membrane disruption
•nuclear shrinkage (pyknosis)

52. Cellular Injury…
Late changes
•nuclear dissolution (karyolysis)
•nuclear break up (karyorrhexis)
•lysosome rupture.
Death of the cell will follow the
development of the late morphological
changes.

53. General mechanism of cell
injury
The mechanism by which injurious agents cause
injury and death are complex.
•some agents such as heat produce direct cell injury
and other factors indirectly.
•there are at least three major mechanisms in
which injurious agents exert their effects.

54. General mechanism of cell
injury…
Three major mechanisms in which injurious
agents exert their effects;
•hypoxia and ATP depletion
•free radical formation and
•disruption of intracellular calcium homeostasis

55. Pathogenesis of cell
injury:
Hypoxic and ischemic injury to the cells occur through:-
ATP depletion
Over production of oxygen –derived free radicals due to
imbalance between free radicals generation and radical
defense system.

56. Pathogenesis of cell
injury:
Other mechanisms caused by all forms of cell injury
include:-
Defect in membrane selective permeability
Damage of the nucleus
Increased intracellular ca+ and loss of ca+
homeostasis that result from damage of both cell
membrane & mitochondrial membrane and ER.
The increased intracellular Ca+ cause activation of
degenerative cellular enzymes as protease,
ATPase, phospholipase and endonuclease.
(that cause damage & mutation of the nucleus)

58. HYPOXIA
Ischemia ( loss of blood
supply ).
Inadequate oxygenation
( cardiorespiratoryfailure ).
Loss of oxygen-carrying capacity of the
blood anemia
CO poisoning ).

59. HYPOXIC INJURY
•LossofoxidativephosphorylationandATP
generationbymitochondria.
•DecreasedATP(withincreaseinAMP):stimulating
fructokinaseandphosphorylation,resultingin
aerobicglycolysis.
•Depletedglycogen.
•ReducedintracellularpH:Lacticacidandinorganic
phosphate.
•Clumpingofnuclearchromatin.

60. Four biochemical themes
•Oxygen-derived free radicals.
•Loss of calcium homeostasis and
increased intracellular calcium.
•ATP depletion.
•Defects in membrane permeability.

61. Free radicals
Formation of free radicals
Normal metabolic processes
(mitochondria, phagocytosis)
Radiant energy
Drugs / other exogenous
compounds

62. Free radicals

63. Cell Injury Caused by Oxygen
Free Radicals
• Superoxide anion
–may be formed via the cytochrome P450 system,
which metabolizes many drugs and toxins –
removed by superoxide dismutase
• Hydrogen peroxide–removed by catalase or
glutathione peroxidase
• Hydroxyl radical (.OH)

64. Effects of Free Radicals
• Lipid peroxidation of membranes
• Oxidative modification of proteins
• DNA damage

65. Mechanism Of Bacterial And Viral
Injury
Byproductionofcytotoxiclymphokins&activationof
lyticcomplementsubstance
Directeffectofbacterialtoxinsonthecellmembrane&
mitochondrialdamage,throughincorporationofviral
genometocellDNAandtheiralteration
Irreversiblemitochondrialdamage.

66. Cellular death
Death is the cessation of life of the cell
•cell death can involve apoptosis(from Greek
word apofor apartand ptosisfor fallen) or
necrosis.
•apoptoticcell death is a controlled cell
destruction.
•necrosisrefers to cell death in an organ or
tissue that is still part of living person.

67. Apoptosis
It is an active process of cellular self destruction in
both normal and pathologic tissue changes
•it is controlled by the system of CASPASES
•initiator (apical) caspases and effectors(executioner)
caspases.
•initiator caspases like (CASP2, CASP8, CASP9 and
CASP10)
•effectors caspases like (CASP3, CASP6 and CASP7)

68. Apoptosis
•Failureofapoptosiswillleadtocancer
developmentandautoimmunediseases
•Unwantedapoptosiscanleadtoischemiaand
Alzheimers’disease,prakinsondiseaseand
amyotrophiclateralsclerosis(ALS)

69. Apoptosis…
Apoptosis determines the size, patterning, function of
many tissues; It is responsible in
•embryonic development
•neurons dying in synaptogenesis
•lymphocytes dyingduring receptor repertoire
selection
•in endocrine-dependent tissues undergoing atrophic
change (endometrial cell loss, mammary glands)
•production of free radical in haemopoietic cells

70. Apoptosis…
Examples of pathological apoptosis:
•tumours:the balance between apoptosis and
cell proliferation is disturbed in neoplasia
•atrophy: cell loss in atrophic tissues is by
apoptosis (viral illness: e.g. hepatitis—
individual hepatocytes, HIV)

71. Apoptosis…
Morphologically
•apoptoticcellsshrinkandthenucleus
condenses.
•theorganellesandnucleusbreak.
•thecellbreaksintofragmentscalledapoptotic
bodieswithligandsontheirsurface
•phagocytesrecognizethemandengulf

72. Initiation for apoptosis
Factors predisposes to apoptosis
Nontoxic stimulican lead to apoptosis
Loss ofgrowth factors.
Direct action ofcytokines (e.g., tumor necrosis factor)
Immune systemaction (e.g., natural killer cells or
cytotoxic T lymphocytes).
Viral infection.
Adult tissue homeostasis .
Sublethal damageto the cells (e.g., by ionizing radiation,
hyperthermia, toxins.)
Loss of cell-cell or cell-matrix attachments.

73. ROLE (VALUE)OF
APOPTOSIS
1-Defense:
Againstnonselfmulticellularorganisms(cellcommits
suicidewheninfectedbyavirusmayprotectothercells
fromfurtherspreadofthevirus)
2-Digestion:
ThecellularDNAdestroythegeneticinformationofany
externalstimulus.
3-Protecting:
Protectionoftheorganismfromunregulatedgrowthof
individualcells

74. Major criteria of
Apoptosis
Morphological changes
Chromatin condensation
DNA fragmentation
Cell death

75. Necrosis
It is the sum of cellular changes after local cell
death
•karyolysis(nuclear dissolution from the action
of hydrolytic enzymes
•karyorhexis–the fragmentation of the
nucleus into clear dust takes place.

76. General effects of necrosis
1.Releaseofenzymesfromthebreakdown
tissueintothebloodformsthebasisofclinical
testsfordiagnosise.g.detectionof
transamenaseinmyocardialinfarctionand
livernecrosisinhepatitis.
2.Absorption of dead products into the
circulation leads to leukocytosis and fever (Not
diagnostic).

77. Types of Necrosis:
•Coagulative–e.g. Infarction
•Liquifactive-Brain, abscess
•Caseous-Bacterial / Tuberculosis
•Gangrene-With infection
•Fatty necrosis -found in the breast, pancreas
and other abdominal structures

78. Types of Necrosis…
Coagulative necrosis
•denaturation of intracellular protein (analogous to
boiling the white of an egg).
•the cells show the microscopic features of cell death.
•architecture of the tissue and cell ghosts remain
•is the commonest type seen in e.g. the kidney and
heart, and is usually caused by ischaemia.

79. Renal Infarction -
Coagulative

80. Splenic Infarction -
Coagulative necrosis

81. Types of Necrosis …
Caseous necrosis
•Subset of coagulative necrosis
•TB
•Cheesy, white
•Surrounded by inflammatory cells
(granulomatous reaction)
•Complete destruction of tissue

82. Extensive
Caseous necrosis
Tuberculosis

83. Caseous necrosis -
Tuberculosis

84. Types of Necrosis …
Liquefactive (colliquative) necrosis
•this is characterised by tissue softening with
destruction of architecture.
•the result is an accumulation of semi-fluid tissue.
•it is usually seen in the brain and spinal cord.

85. Liquifactive necrosis…
The necrosed tissue undergoes rapid softening e.g. infarction
of the nervoustissue 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 abscessoccurs 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.

86. Stroke-Liquifactive
necrosis

87. Liver abscess:
Liquifactive necrosis

88. Infarction -Adrenal
gland:

89. Types of Necrosis …
Fat necrosis
•direct trauma (common in the fatty tissues of the
female breast)
•enzyme release from the diseased pancreas.
•adipocytes rupture and released fat undergoes
lipolysis catalysed by lipases.
•macrophages ingest the oily material
•combination of calcium with the released fatty acids
(saponification).

90. Types of Necrosis …
Fibrinoid necrosis
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 vesselsin malignant
hypertension

91. FIBRINOID NECROSIS

92. Types of Necrosis …
Zenker’s necrosis:
Of the rectus abdominus muscle and
diaphragm as a complication of :
bacterial infectionparticularly typhoid fever.
The striated muscles lose its striation,
swell and fuse together in homogeneous
structureless mass.

93. Gangrene
Definition:necrosisofbigtissuewithsuperadded
putrefaction,black,foul-smellingappearance.
Necrosisofbigtissueputrefactiveblack,green
Ororganorlimborganismsinfectionappearance
(blackorgreenduetobreakdownofhaemoglobin)
Types of Necrosis …

94. Typesof Necrosis …
Gangrenous necrosis (gangrene)
•coagulativenecrosisoftissuesisassociatedwithsuperadded
infectionbyputrefactiveanaerobicGram-positivebacteria
Clostridiumspp.
•gangrenoustissueisfoulsmellingandblack.
•thebacteriaproducetoxinswhichdestroycollagenand
enabletheinfectiontospreadrapidly;
•itcanbecomesystemic(i.e.reachthebloodstream,
septicaemia).

95. TypesofNecrosis…
Gangrenous necrosis (gangrene)
•gangrene can be dry, wet or gaseous
dry gangrene is usually due to a coagulative necrosis
Wet gangrene develops when neutrophils invade the site
and cause liquefactive necrosis
Gas gangrene is due to bacterial infection of injured tissue by
clostridium perfringens

96. a.Drygangrene:
Conditions:onlyoccursontheskinsurface
followingarterialobstruction.Itis
particularlyliabletoaffectthelimbs,
especiallythetoes.
Character:mummification
Types of gangrene:

97. Dry gangrene

98. Gangrene -Amputated
Diabetic foot

99. b.Wetgangrene:
Conditions:Botharterialandvenous
obstruction;wetinenvironment;
Character:wetswollen,foul-smelling,black
orgreen.
Commonly in small intestine, appendix, lung,
and uterus, also in limbs.
Types of gangrene:

100. Moist gangrene

101. c.Gasgangrene:
Conditions:deepcontaminatedwoundsinwhichthereis
considerablemuscledamagedbygasformationbacteria.
Character:swollenobviously,gasbubblesformation.The
infectionrapidlyspreadsandthereisassociatedsevere
toxaemia.
Only occasionally in civilian practice but is a serious
complication of war wounds.
Types of gangrene:

102. 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).

103. 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 unabsorbedcaseous lesions and fat necrosis usually
becomes heavily calcified (dystrophic calcification).
4-when the necrotic tissue is infected with putrefactive
Organism------Gangrene

104. Sequels(results) of
Necrosis:
•Cell Death
•Necrosis
•Autolysis
•Phagocytosis
•Organization & fibrous repair.

106. Apoptosis and Necrosis
(prev.diagram)
•The sequential ultrastructural changes seen in
necrosis (left)and apoptosis (right). In
•apoptosis, the initial changes consist of nuclear
chromatin condensation and fragmentation,
•followed by cytoplasmic budding and phagocytosis
of the extruded apoptotic bodies.
•Signs of cytoplasmic blebs, and digestion and
leakage of cellular components.

107. Features of Necrosis and Apoptosis
FeatureNecrosisApoptosis
Cell size Enlarged Reduced
Nucleus Pyknosis/karyorrhexis/karyolysis Fragmentation
Plasma membraneDisrupted Intact
Cellular contentsEnzymatic digestionIntact
Inflammation Frequent None

108. Hydropic change in
ischemic -kidney

109. Ageing

110. Ageing
•“Progressive time related loss of structural
and functional capacity of cells leading to
death”
•Senescence, Senility, Senile changes.
•Ageing of a person is intimately related to
cellular ageing.

111. Theories of aging
•Developmental –genetic theories
Resides with genetic influences that
determine physical condition, occurrence of
disease, age of death, cause of death and
other factor contributing to longevity
•Stochastic theories

112. Theories of aging…
•Stochastic theories-
Propose that aging is caused by random
damage to vital cell molecules
Somatic mutation theory of aging
Oxidative free radical theory
The wear and tear theory

113. Factors affecting
Ageing:
•Genetic –Clock genes, (fibroblasts)
•Diet –malnutrition, obesity etc.
•Social conditions -
•Diseases –Atherosclerosis, diabetes etc.
•Werner’s syndrome.

114. Cellular mechanisms of
ageing
•Cross linking proteins & DNA.
•Accumulation of toxic by-products.
•Ageing genes.
•Loss of repair mechanism.
•Free radicle injury
•Telomerase shortening.

115. Telomerase in ageing:
Germ
Cells
Somatic
Cells

116. Ageing –changes:
•Gradual atrophy of tissues and organs.
•Dementia
•Loss of skin elasticity
•Greying and Loss of hair
•BV damage –atherosclerosis/bruising.
•Loss of Lens elasticity opacity vision
•Lipofuscinpigment deposition –Brown atrophy in
vital organs.

117. Pathology of elderly

118. Factors affecting
ageing:
Increase ageing
•Stress
•Infections
•Diseases
•Malnutrition
•Accidents

119. Factors affecting
ageing:
Decrease ageing
•Diminished stress response.
•Diminished immune response.
•Good health.

120. Conclusions:
•Cellular Injury -Various causes
•Reversible Injury Adaptations
Hypertrophy, Hyperplasia, Atrophy
Accumulations -Hydropic, hyaline, fat..
•Irreversible Injury -Necrosis
Coagulative, Liquifactive, Caseous
•Ageing -Causes, Changes, Factors