cell injuryadaptation 2

Cell Injury and Adaptations -2Cell Injury and Adaptations -2

Dr.CSBR.Prasad, M.D.

AtrophyAtrophy

Cell number Cell size

Cell substanceOrgan / tissue size

AtrophyAtrophy

Def: Shrinkage in the size of the cell by the loss of cell substance

As a result organ / tissue size diminishes

Ex: Skeletal muscle in disuseIschemia causing reduction in size of a limb

AtrophyAtrophy

Because of atrophy of cells, organ / tissue size diminishesAtrophic cells have diminished function but they are not deadThere may be over all loss of number of cells in an organIt’s a retreat for the cells to a smaller size at which survival is still possible

AtrophyAtrophy

Causes: Causes: 1. < work load2. < blood supply3. Inadequate nutrition4. Loss of endocrine stimulation 5. Aging

AtrophyAtrophy

Mechanism:Mechanism:Regulation of protein degradation play a

key role in atrophyThere are two proteolytic systems There are two proteolytic systems

involved in degradationinvolved in degradation1. Lysosomes2. Ubiquitin-proteasome pathway

AtrophyAtrophy

Microscopic changes:Microscopic changes:1. Decrease in size of the cell2. Marked increase in number of

autophagic vacuoles3. Lipofuchsin accumulation

Atrophy Atrophy

Cancer cachexia:Cancer cachexia:

Proteasome pathway is activated in hypercatabolic

state including cancer cachexia

Lipofuscin granules in a cardiac myocyteLipofuscin granules in a cardiac myocyte

HypertrophyHypertrophy

Cell numberCell size


Hypertrophy Hypertrophy

• Increase in size of the cells• Increase in organ size and tissue size• NO NEW CELLSNO NEW CELLS


Causes: • Increased functional demand Increased functional demand • Specific hormonal stimulusSpecific hormonal stimulus


Basic Mechanisms: 1.1. Increased synthesis of structural proteins Increased synthesis of structural proteins

/ organelle/ organelle2.2. Increased DNA contentIncreased DNA content3.3. Rarely - a change in cellular phenotypeRarely - a change in cellular phenotype

Mechanisms of myocardial hypertrophy


Types:1.1. Physiological Physiological 2.2. Pathological Pathological

Hypertrophy Hypertrophy Types:Types:

1-Physiological1-Physiological Eg: Eg: - Uterus during pregnancy- Uterus during pregnancy- Exercise induced increase in muscle bulk- Exercise induced increase in muscle bulk

2-Pathological2-Pathological Eg: Eg:- Concentric hypertrophy of LV in HTN / AS / AR- Concentric hypertrophy of LV in HTN / AS / AR- Hypertrophy of residual cardiac myocytes after MI- Hypertrophy of residual cardiac myocytes after MI- Hypertrophy of smooth muscle in the intestinal wall proximal - Hypertrophy of smooth muscle in the intestinal wall proximal

to obstructionto obstruction

Note:Note: some times hypertrophy and hyperplasia may occur some times hypertrophy and hyperplasia may occur togethertogether

eg: uterus in pregnancyeg: uterus in pregnancy


Whatever the mechanism, after a stage, Whatever the mechanism, after a stage, degenerative changes take placedegenerative changes take place

Eg: fragmentation and loss of myofilamentary contractile protein

This may be due to increased demand for blood supply which is finite

HypertrophyHypertrophy

Physiologic hypertrophy of Physiologic hypertrophy of the uterus during pregnancythe uterus during pregnancy

Sturge-Weber syndrome

HyperplasiaHyperplasia

Cell numberCell size


Hyperplasia Hyperplasia

• Increase in number of cells• Increase in organ size and tissue size• NEW CELLS will formNEW CELLS will form• New cell form from stem cells / resting

cell


Types:Types:• Physiological

1.1. HormonalHormonal eg: EM, Breast, Uterus in pregnancy 2.2. CompensatoryCompensatory eg: Partial hepatectomy, wound

healing• Pathological

EM hyperplasias, adrenal cortical hyperplasia due to pituitary tumor; TSH secreting adenoma of pituitary, Stimulatory Ig against TSH receptor---> thyroid hyperplasia; Androgens & prostate


Pathological - Mostly due to excessive hormone stimulation or

growth factor stimulation eg: EM proliferation- Increased sensitivity to growth factors eg: HPV infection of skin

Note: pathological hyperplasias constitute a fertile soil for possible future cancer

Eg: EM hyperplasia HPV infection and cervical cancer


Main difference between hyperplasia and Main difference between hyperplasia and cancers:cancers:

In Hyperplasia : proliferation is controlledIn Cancers : proliferation is uncontrolled

Clinical Clinical ApplicationsApplications

1 - In a patient with bleeding PV, US 1 - In a patient with bleeding PV, US showed endometrial hyperplasia. showed endometrial hyperplasia.

• What do you elicit in history?• Assume that this patient had an ovarian tumor.

Can you guess what is the nature of tumor? Collaterals:• What do you call such tumors? Can you give

some more examples? • Unfortunately, endometrial biopsy turned out to

be endometrial carcinoma. Surgeon considered oophorectomy as a part of treatment. What is your comment?

2 - Earlier breast carcinomas were 2 - Earlier breast carcinomas were treated by mastectomy and treated by mastectomy and oophorectomy and adrenalectomy.oophorectomy and adrenalectomy.

• How oophorectomy will benefit the patient?

Metaplasia Metaplasia

Metaplasia Metaplasia Def: one adult cell type is replaced by

another adult cell type

It’s a reversiblereversible changeIt may involve epitheliumepithelium or

mesenchymalmesenchymal tissue


Preference to the fittest for a given injury


Mechanism: Mechanism: Arises from genetic reprogramming of

epithelial stem cells or of undifferentiated mesenchymal cells

Metaplasia Metaplasia Examples: Examples:

Smoking : squamous metaplasia of respiratory epithelium

Vit-A deficiency: squamous metaplasia of respiratory epithelium

Chronic cervical infections: squamous metaplasia of endocervical epithelium

Urinary stones: squamous metaplasia of urotheliumGERD: gatric / intestinal metaplasia in squamous

epithelium of esophagusGastritis: Mucous metaplasia in gastric epithelium

Metaplasia Metaplasia Also occur in mesenchymal tissueBUT - It’s not an adaptive response

Examples: Examples:

- bone & cartilage formation in soft tissues after an injury

- tumor metaplasias

Metaplasia Metaplasia Consequences: Consequences:

1. Loss of protective mechanism2. Fertile soil for cancers

Metaplasia in esophagusMetaplasia in esophagus

DysplasiaDysplasia

Intracellular accumulationsIntracellular accumulations

Intracellular accumulationsIntracellular accumulationsAccumulation of abnormal amounts of various

substancesThree categories:Three categories:1- Normal cellular constituents accumulated in

excess eg: H2O, Lipid, Proteins, CHO

2- Accumulation of abnormal substanceExogenous eg: minerals, infectious agentsEndogenous eg: abnormal synthesis, abnormal metabolism

3- Pigment

Intracellular accumulationsIntracellular accumulationsSubstances accumulated:Substances accumulated:1. Transient accumulations2. Permanent accumulations• Harmless• Toxic1. Cytoplasm2. Nucleus

Intracellular accumulationsIntracellular accumulationsProcesses that result in intracellular accumulations:Processes that result in intracellular accumulations:

1. Normal endogenous product at the normal rate / induced rate but with reduced rate of removal

2. Normal / abnormal endogenous products accumulate bec’ of defective metabolism (packge/transport/secretion). It’s usually a gentic defect

3. Accumulation of abnormal exogenous substance bec’ cell has no machinary to degrade or export to other sites


If Overload is due toIf Overload is due to:Systemic derangementsSystemic derangements: reversibleGenetic defectGenetic defect: irreversible - progressive


Accumulation of LIPIDSAccumulation of LIPIDS:Any class of lipids may get accumulatedAny class of lipids may get accumulatedTriglyceridesTriglyceridesCholesterol / cholesterol esterCholesterol / cholesterol esterPhospholipidsPhospholipidsComplex of lipids & carbohydratesComplex of lipids & carbohydrates (Eg: Lysosomal storage diseases)(Eg: Lysosomal storage diseases)


FATTY CHANGE: (STEATOSIS)FATTY CHANGE: (STEATOSIS)Accumulation of triglyceridesAccumulation of triglyceridesUsually seen in Usually seen in liver liver (can also occur in kidney, heart, skeletal (can also occur in kidney, heart, skeletal

muscle)muscle)


FATTY CHANGE: (STEATOSIS)FATTY CHANGE: (STEATOSIS)

Causes:Causes:ToxinsToxinsAlcoholAlcoholPEMPEMDMDMObesityObesityAnoxiaAnoxia


FATTY CHANGE: FATTY CHANGE: LiverLiver

Significance: Significance: depends on thedepends on the

CauseCause Severity of accumulationSeverity of accumulation NASH NASH (may lead to cirrhosis, HCC)(may lead to cirrhosis, HCC)


FATTY CHANGE: FATTY CHANGE: LiverLiverMorphology:Morphology:Uniform enlargementUniform enlargementYellowish with greater accumulation of fatYellowish with greater accumulation of fatBorders are sharpBorders are sharpCapsule is stretchedCapsule is stretchedc/s greasy c/s greasy


FATTY CHANGE: FATTY CHANGE: LiverLiverMicroscopy:Microscopy:Minute membrane bound vesiclesMinute membrane bound vesiclesFirst seen around the nucleusFirst seen around the nucleusWith progressive accumulation cells With progressive accumulation cells

resembles adipocyteresembles adipocyteFatty cystsFatty cysts


FATTY CHANGE: FATTY CHANGE: HeartHeartGross:Gross:Two patterns of accumulationsTwo patterns of accumulationsTigroid effect (hypoxia) Tigroid effect (hypoxia)

alternating layers of brown and yellowalternating layers of brown and yellow

Yellow heart (Diphtheria, severe hypoxia)Yellow heart (Diphtheria, severe hypoxia)Diffuse accumulation in almost all cellsDiffuse accumulation in almost all cells


FATTY CHANGE: FATTY CHANGE: HeartHeartMicroscopy:Microscopy:Small clear vaucoles in the cardiac Small clear vaucoles in the cardiac

myocytesmyocytes


FATTY CHANGE: FATTY CHANGE: DDDDIntracellular accumulations of Intracellular accumulations of fatfat, , glycogenglycogen

and and waterwater cannot be differentiated by cannot be differentiated by routine histologyroutine histology

Special stains are needed for differentiationSpecial stains are needed for differentiation

Intracellular accumulationsIntracellular accumulationsFATTY CHANGE: FATTY CHANGE: DDDDSpecial stains that will help to differentiate fat and Special stains that will help to differentiate fat and

glycogenglycogenSudan III / IVSudan III / IV fat – red / orange fat – red / orangeSudan blackSudan black fat – black fat – black Oil Red – OOil Red – O fat – red / orange fat – red / orangeNile blue ANile blue A fat – red fat – red PASPAS stains glycogen (pink) stains glycogen (pink)

NoteNote: : for the demonstration of fat for the demonstration of fat frozen sections are used.frozen sections are used.

Atherosclerosis, Oil red - O


Cholesterol / cholestryl ester:Cholesterol / cholestryl ester:Every cell uses choleterol for the synthesis of its Every cell uses choleterol for the synthesis of its

cell membranecell membraneAccumulation of cholesterol is always pathologicalAccumulation of cholesterol is always pathologicalConditions:Conditions:CholesterolosisCholesterolosisASASXanthomasXanthomasInflammation / necrosisInflammation / necrosisNiemann – Pick disease type-CNiemann – Pick disease type-C


Atherosclerosis:Atherosclerosis:Seen in large and medium sized arteriesSeen in large and medium sized arteriesMØ smooth muscle cells accumulate with MØ smooth muscle cells accumulate with

in the intimal layerin the intimal layerThey are filled with lipid vacuoles – Foam They are filled with lipid vacuoles – Foam

cellscellsGrossGross: produces yellow plaques: produces yellow plaquesCholesterol clefts may be seenCholesterol clefts may be seen

Fatty streaks

Varying grades of AS

AS involving coronary artery – cholesterol clefts

AS involving coronary artery –

Foamy macrophages, cholesterol clefts

Cholesterol clefts


Xanthomas:Xanthomas:Intracellular accumulation of fat in MØIntracellular accumulation of fat in MØSome hereditary hyperlipidemiasSome hereditary hyperlipidemiasFoam cells are seen in the subepithelial Foam cells are seen in the subepithelial

connective tissueconnective tissueClinically they produce tumorsClinically they produce tumors


Inflammation / necrosis:Inflammation / necrosis:foamy MØ are seen at these sitesfoamy MØ are seen at these sitesWhen they are in excessive number they When they are in excessive number they

produce yellowish colour to the siteproduce yellowish colour to the siteEg:Eg:Xanthogranulomatous pyelonphritisXanthogranulomatous pyelonphritisxanthogranulomasxanthogranulomas

Xanthogranulomatous pyelonephritis


Cholesterolosis:Cholesterolosis:Focal accumulations of foamy MØ in the Focal accumulations of foamy MØ in the

lamina propria of gall bladderlamina propria of gall bladder

Cholesterolosis of Gall Bladder

Tendinous xanthomas

Erruptive xanthomas

Xanthelasma

Mucopolysaccharidoses - 1

Niemann-Pick Disease

Waterhouse-Friderichsen Syndrome

Wegener’s granulomatosis

cell injuryadaptation 2

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