degenration and necrosis

8/2/2019 Degenration and Necrosis

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Presented by :

Dr. Kush Pathak


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DEGENERATION AND

NECROSIS


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Contents

1. Introduction

2. Causes of cell injury

3. Biochemical mechanism of cell injury

4. Reversible & irreversible cell injury

5. Degeneration6. Types of degeneration

7. Necrosis

8.Termination of necrosis


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Introduction

Cellsfunctions are complex and delicate.

Main functions of cells-

1 Maintenance of permeability of cell membrane- water &electrolyte balance.

2 Aerobic respiration & production of ATPmain function

of mitochondria.

3 Protein synthesis.

4 Preservation of integrity of genetic apparatus of cell.


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Normal homeostasis- when cell

is able to handle the normal

physiological demands.

When the physiological demand

exceeds normal / any

pathological stimuli may bring

about physiologic and

morphologic cellular adaptations

( hypertrophy,

atrophy,hyperplasia,

metaplasia)


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When stimuli still exceeds,

where cellular adaptation is not

possible it leads to cell injury.

Outcomes of cell injury


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Causes of cell injury

1 Hypoxia-

-common cause of cell injury

&

cell death.

Causes- cardiac failure,respiratory failure, anemia.


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2. Physical agents-

-mech trauma, radiation, electric shock.

3. Chemical agents-

-poisonous sub like cyanide, mercuric salts.

-high cons of O2

-hypertonic cons of glucose / salts.

4. Infectious agents--bacteria, virus, fungi causes cell injury.


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5. Immunologic reactions-

- Immune system protects the body against the foreign

material.

- Some immune reactions can cause cell injury eg-

anaphylaxis reactions.

6. Genetic defects-

Any alteration at the level of chromosome or DNA level can

cause cell injury.


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Mechanism of cell injury:

1. Cellular responses to injurious stimuli depends on type ofinjury, duration & its severity.

2. Same injury has different outcome , depending on the celltype

Striated skeletal muscle of leg

Complete

ischemia

Accommodate 2-3 hrswithout irreversibleinjury

Cardiac muscle

After 20-30 min

Cell dies


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3. Celluar functions are lost far before cell death occurs &

morphological changes of cell injury lag far behind both.


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1. ATP depletion-

Results in rapid shutdown of most critical homostatic

pathways

ATP required for cellular osmolarity, transport processes,

protein synthesis.2 O2 deprivation / reactive O2 species-

Lack of O2 and reactive O2 species are also responsible for

cell death.

- Free radicals causes lipid peroxidation & deleterious effects

on cell struc like DNA fragmentation, protein synthesis.

BIOCHEMICAL MECHANISM OF CELL INJURY


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3 Loss of Ca+2

- Cytosolic free Ca+2 is maintained by ATP dependant ca+2 transporters at

a cons 10,000 times lower than cons of extracellular Ca+2.

- Ischemia / toxins allow a net influx of extracellular ca+2 across the

plasma membrane followed by release of ca+2

for the intracellularstores.


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4. Defects in membrane permeability

Bacterial toxins, viral proteins , physical & chemical agents

leads to loss of membrane barrier

Breakdown of cons gradient necessary to maintain normal

metabolic activities

5 Mi h d i l d


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5. Mitochondrial damage

(A) Mitochondria required for oxidative metabolism(B) cytosolic calcium, oxidative stress, lipid breakdown products

Formation of high conductance channels of innermitochondrial membrane c/a mitochondrial permeabilitytransition

Non selective pores allow proton gradient across themitochondrial membrane, this prevents ATP generation


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normal physiological excess physiologicalstress

demand

Normal cell

normal homeostasis cellular adaptation

Reversible injury

Persistent stimuli


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irreversible injury

cell death

necrosis apoptosis


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Reversible cell injury

Degeneration

In Latin degeneration means- deterioration or passing

from higher to lower level.

A retrogressive reversible pathological change in cells or

tissues in consequence for which their functions are

impaired.

h l l h f ibl ll i j


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Morphology- the ultrastructural changes of reversible cell injury-1 plasma membrane alteration- blunting of microvilli, loosening of

intercellular attachments.

2 mitochondrial changes- swelling & appearance of phospholipids rich

amorphous densities.

3 Dilation of ER

4 Nuclear alteration


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Types of degeneration(a) Disturbances in protein metabolism-

1. Cloudy swelling

2. Hydropic degeneration

3. Hyaline degeneration

4. Zenkers degeneration

5. Amyloid degeneration

(b) Disturbances in carbohydrate metabolism

1. Mucoid degeneration

(c) Disturbances in fat metabolism

1. Fatty degeneration


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1 Cloudy swelling

- First manifestation of almost all forms of cell injury.

- Causes- back toxins, chemicals, burns, high fever- It results from impaired regulation of cellular volume, especially

for Na.

- Na regulation operates at 2 levels

- plasma membrane

- Na pump on plasma membrane

- Injurious agents may interfere with these regulatory mechanism &result in accumulation of Na in cell.


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Gross appearance-

- affected organ is enlarged

- cut surface appears opaque, cloudy & pale .

Microscopic feature-

-Cells presents with granular & eosinophilic material

cloudy swelling

(kidney)


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2. Hydropic degeneration / vacuolar degen

- Severe form of cloudy swelling characterized by vacuolization of cells due toimbibition of large quantity of water in cell cytoplasm.

Causes - viral infection

- in kidney due to water & electrolytic imbalance.

-in hepatic cells due to infective hepatitis.

Pathogenesis-

- Toxic agents which interfere with semi permeability of cell membrane

water imbibitions


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- damaged mitochondria impaired energyproduction

altered cell permeability

Na in cell & k in cell

water in cell

hydropic degeneration


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Gross app

-Affected organ is swollen

- Cut surface appears opaque, pale,soft

Microscopic features-

-Cells appear clear due to watercontent

-Cytoplasm is vacuolated


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3 Hyaline degeneration-

Hyalinederived from Greek wordhyalos ( glass)

Hyaline indicates a glassy, homogenous, translucent appearance ofcytoplasm.

Hyaline stains bright red with eosin, blue or green with trichrome stain.

Cell organelle mainly involved are smooth ER, agglomeration of SERcorresponds to hyaline bodies in light microscopy.

- 2 types cellular hyalinization

connective tissue hyaline.

Hyaline degenration


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(a) Cellular hyalinization-

- Hyaline or glassy appearance of cell is due to coagulated proteins.Seen in following condition

In kidneyin the cells of renal tubules in nephritis.

these droplets are small, spherical.

Hyaline droplets


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In liver in viral hepatitishyaline inclusions arefound

-in alcoholic cirrhosisappears as dark irregularnetwork in

cytoplasm c/a Mallory

bodies.


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(b) Connective tissue hyalinization

- Caused by agglomeration & swelling of collagen- Found in scar of fibrocollagenous tissue.


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4 Zenkers degeneration-Commonly seen in striated muscles- skeletal & cardiac muscle.

gross app-

Muscle is thin, translucent & glossy in appearance

Microscopic app--loss of cross striations

-muscle cells appear coarse & clumped due to coagulation of sarcoplasm.

If the damage to muscle cell is irreversible the change is followed bycoagulation necrosis.

5 A l id d ti


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5 Amyloid degeneration

amyl starch starch like

oid - resembling

-Appears as amorphous, homogenous, translucent, eosinophilic.

- Usually found in walls of bv & basement mem.

-It is composed of 2 types of complex proteins

fibril protein P component

90% 10%


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- with congo red & polarised lightamyliod shows apple greenbirefringence due to cross -pleated sheet configuration


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(a) Fibril protein-

- Fibrils are delicate, non branching filaments measuring 7.5- 10nm in diameter& having indefinite length.

- In x-ray crystallographic analysis, the fibrils presents as - pleated sheetconfiguration which produces periodicity. this is characteristic feature ofamyloid.

- 2 types of amyloid fibril protein are1 AL (amyloid light chain)

2 AA (amyloid associated protein)

(b) P component-

- Non fibrillar

-In electron microscopy appears as pentagonal profile.


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Pathologic effects of amyloid-

- creates pressure onadjacent cells & causesatrophy.

- on blood vessels

narrowing of the vessels.

Amyloid plaque


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6. Mucoid degeneration

The degeneration of connective tissue into a gelatinous or mucoid

substance.-Mucous- is viscous watery secretion of mucous glands in a loosecombination of proteins & mucopolysaccharide.

- Mucin- is a glycoprotein & chief constituent of mucous.

Mucoid degeneration is excessive secretion of mucous associatedwith degeneration of cells


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- mucous is produced by epithelial cells of mucous membrane,mucous glands & CT cells in fetus.

- Epithelial mucin

Catarrhal inflammation of mucous membrane of respiratory

tractobstruction of duct leading to mucocele in oral cavity


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- CT mucins eg

-mucoid degeneration in some tumorsin myxomas,

neurofibromas


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7. fatty degeneration

Abnormal accumulation of small droplets with in the previouslyinjured/ diseased parenchymal cells, where normally fat is notvisible

- organs involved are liver, kidney, heart

etiology-

-anoxia-toxic agents like chloroform

- starvation


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(a) Fatty degeneration of liver

gross app-

-enlargement of liver

-appears pale , soft

- cut surface shows yellowish areas

Microscopic features:

-In fatty degeneration, small fat droplets appear in cytoplasm withoutdisplacement of nucleus.

-In fatty in filteration fat droplets fuse & push the nucleus in one corner givingsignet ring appearance.


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Fatty change in liver


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(b) Fatty degeneration in heart

The accumulation of fat globules within the cells of a bodily organ, suchas the liver or heart, resulting in deterioration of tissue and diminished

functioning of the affected organ

gross app-

-fatty yellow band alternating with healthy band of myocardium or it can bediffuse degeneration of entire myocardium

-loss of muscular tone

microscopic app--fat droplets arranged in rows along the length of muscle cell


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Irreversible cell injuryNecrosis

- Necrosis refers to a sequence of morphological changes that followS cell death inliving tissue.

gross app-

-normal translucency of living tissue is lost. Tissue appears opaque, yellowish in

color

morphological appearance in necrosis is result of

-enzymatic digestion of the cell

-denaturation of protein

This process requires hrs to develop, so there is no detectable change in cells in earlystages.

Morphological changes-


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Morphological changes

(a) Cytoplasmic changes-

Dead cells show eosinophilia.

Cells may have a glassyhomogenous app than viable cells ,mainly due to of glycogen particle

enzymes degrade the organelles ofcytoplasm, cytoplasm becomesvacuolated & appears moth eaten.

Nuclear changes-


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Nuclear changes-

Seen due to non specific breakdownof DNA

(a) karyolysis

-basophilia of the chromatin fadessecondary to DNAase activity

-nuclear chromatin undergoesdissolution gradually

(b) pyknosis

-nuclear shrinkage & basophilia

-DNA condenses into a solidshrunken mass & loss of nucleardetails

(c) karyorrhexis

-pyknotic nuclei fragments & totallydisappears

h d d ll h d h l h


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- once the dead cells have undergone these early changes, mass ofnecrotic tissue exhibits distinctive morphological patterndepending on enzymatic catabolism / protein denaturation.

- when denaturation predominates coagulation necrosis develops

- in case of enzymatic degradation liquefaction necrosis develops.


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Diagnosis of necrosis by biochemical means

- as necrosis occurs various solu sub like enzymes, diffuse out of

cells & absorbed in blood stream . Their detection aids in clinicaldiagnosis.

eg- 1 after skeletal muscle necrosis- raised plasma level of cratininephosphokinase (cpk)


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2. - In myocardial infarction - in SGOT (glutamateoxaloacetate transaminase)

- in CPK (Creatinine phosphokinase)

- in LDH (lactate dehydrogenase)


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1 Coagulation necrosis


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1. Coagulation necrosis-

Caused by irreversible injury, characterized by coagulation ofproteins of dead cells by intracellular enzymes

cause- sudden cessation of blood flow (ischemia)- hypoxia

Pathogenesis

injury hypoxia

ATP synthesis

Ph (acidosis)


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degeneration of structural proteins & enzymaticproteins

which blocks the proteolysis of cells

gross app

- foci of coagulative necrosis is yellowish, softer & shrunken.


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microscopic app

- Hallmark of coagulative necrosis is the conversion of normal cellsinto their tomb stones ie., outline of cells are retained so that celltype can be recognized but their cytoplasmic & nuclear details arelost.

- cells appear more eosinophilic

- nuclear changes pyknosis followed by karyolysis


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Normal myocardial cells

Coagulative necrosis


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Large area of coagulativenecrosis

Coagulaulated kidney

f t d f i i i fil d b i fl ll d d ll


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fate necrosed foci is infilterated by inflammatory cells . dead cells arephagocytosed leaving granular debris & fragments of the cells

2. Liquefaction necrosis (colliquative)

- Chacterized by rapid enzymatic digestion & complete destruction of cells & tissue.

cause- hypoxic death of cells in brain

- focal bacterial & fungal infection


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Pathogenesishydrolyticenzymes of cells

complete digestion &destruction of cells & tissues

gross app-

Affected areas is soft withliquified center containingnecrotic debris. Later a cyst wallis formed.

Liquifaction necrosis in brain

microscopic app-


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microscopic app-

Liquifaction necrosis

3 C i


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3. Caseous necrosis

- Is distinctive form of necrosis seen in foci of tuberculous infection.

- In casseous necrosis, cellular structure are lost with production ofcheesy material

Gross app

- Foci of casseous necrosis resembles dry cheese & are soft, granular &yellowish.

- Appearance is partly attributed to lipopolysaccarides present in capsule

of tubercle bacilli


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Microscopic app

Necrosed foci are structure less,eosinophilic

Surrounding tissue showsgranulomatous inflammatory

reaction

Consisting of epithiloid cellswith interspread giant cells oflangerhans & peripherally

lymphocytes

4 Fat necrosis


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4. Fat necrosis- Special form of necrosis which affects adipose tissue

cause

-acute pancreatitis

-trauma to pancreas

pathogenesis acute pancreatitis / trauma

Injury to acinar cells

Release of pancreatic lipase

Digestion of pancreas itself + surrounding adipose tissue


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protease & lipases liquify plasma mem of fat cells

release of triglycerides

triglycerides free fatty acid + glycerol

- damaged adipose cells assume cloudy app due to remaining free fatty acids

- fatty acid can complex with Ca to form Ca soaps


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gross app-appears as yellowish, white firm

deposits.

-formation of Ca soaps imparts firm& chalky white app to necrosed foci.

microscopic app--necrosed cells have cloudy app,

surrounded by inflammatoryreaction.

-formation of Ca soaps is identified as

amorphous, granular & basophilicmaterial.

5. Fibrinoid necrosis


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5 Fibrinoid necrosis

- Is characterized by deposition of fibrin like material .

cause

- hypertension

- peptic ulcer

- autoimmune disease

site

- wall of arterioles / small arteries

microscopically- appears as bright, eosinophilic, hyaline like deposition in vessel wall or

on luminal surface of a peptic ulcer


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Fibrinoid degeneration

i i f i


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Termination of necrosis

- occurs when necrotic area is small

liquefaction by leucocytes / autolysis

lymphatic absorption

- sometimes necrosis is asso with sec infection with pyogenicorganism


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absorption abscess formation

Necrosis

encapsulation calcification fibrosis

when necrotic area dead tissue -repair by filling

is large , repair takes attracts gaps with fibrous

place from periphery Ca from blood + fatty tissue in brain, liver &

to provide a capsule acids heart

of fibrous

tissue

- insoluble Ca soaps


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References

1. Robbins Basic Pathology, 6th Edition.

2. Pathology Rubin & Farber , 1st Edition.

3. Text Book of Pathology, N.C.Dey , 6th Edition.

4. Text Book of Pathology , Harsh Mohan , 3ed Edition.

5. Text Book of Pathology , William Boyed , 8th Edition.


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Thank you

degenration and necrosis

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