Tishk International UniversityScience FacultyMedical Analysis Department

Pathology

Fourth Grade- Spring Semester 2020-2021

Cell injury 1- Cellular Adaptations

Dr. Jalal A. JalalAssistant Professor of Pathology

Objectives

• To understand the principal adaptive responses which are

• Hypertrophy,

• Hyperplasia,

• Atrophy, and

• Metaplasia.

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INTRODUCTION

• As cells encounter physiologic stresses or pathologicstimuli, they can undergo adaptation, achieving anew steady state and preserving viability andfunction.

• The principal adaptive responses are hypertrophy,hyperplasia, atrophy, and metaplasia.

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• If the adaptive capability is exceeded or ifthe external stress is harmful, cell injurydevelops .

• Within certain limits cell injury is reversible,and cells return to a stable baseline;

• however, severe or persistent stress resultsin irreversible cell injury and death of theaffected cells.

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Adapted

Cell

+ Stress

Injury

Normal

cell

Reversibly

injured cell

Irreversibly

Injured cellDead cell

Apoptosis

Necrosis

- Stress

Overview5

• Cell death is one of the most crucial events inthe evolution of disease in any tissue or organ.

• It results from diverse causes, includingischemia (lack of blood flow), infections, toxins,and immune reactions.

• Cell death is also a normal and essentialprocess in embryogenesis, the development oforgans.

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CELLULAR ADAPTATIONS TO STRESS

• Adaptations are reversible changes in the number,size, phenotype, metabolic activity, or functions ofcells in response to changes in their environment.

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• Physiologic adaptations

• usually represent responses of cells tonormal stimulation by hormones orendogenous chemical mediators (e.g., thehormone-induced enlargement of the breastand uterus during pregnancy).

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• Pathologic adaptations

• are responses to stress that allow cells tomodulate their structure and function andthus escape injury. Such adaptations can takeseveral distinct forms.

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Cellular adaptations to stress

1. Hyperplasia (more cells)

2. Hypertrophy (bigger cells)

3. Atrophy (smaller cells)

4. Metaplasia (different type of cells)

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Hypertrophy

• Hypertrophy is an increase in the size of cellsresulting in increase in the size of the organ

• in pure hypertrophy there are no new cells, justbigger cells, enlarged by an increased amount ofstructural proteins and organelles.

• hypertrophy occurs when cells are incapable ofdividing.

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• Hypertrophy can be physiologic orpathologic and is caused either by increasedfunctional demand or by specific hormonalstimulation.

• Hypertrophy and hyperplasia can also occurtogether, and obviously both result in anenlarged organ.

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Hypertrophy

• Thus, the massive physiologic enlargement of theuterus during pregnancy occurs as a consequence ofestrogen-stimulated smooth muscle hypertrophyand smooth muscle hyperplasia.

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• In contrast, the striated muscle cells in boththe skeletal muscle and the heart canundergo only hypertrophy in response toincreased demand because in the adult theyhave limited capacity to divide.

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• Examples of pathologic cellular hypertrophy include the cardiac enlargement that occurs with hypertension.

Left ventricle

↔

Hyperplasia

• hyperplasia is characterized by an increase in cellnumber.

• Hyperplasia is an adaptive response in cells capableof replication.

• Hyperplasia can be physiologic or pathologic.

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The two types of physiologic hyperplasia are:

(1) hormonal hyperplasia, exemplified by theproliferation of the glandular epithelium ofthe female breast at puberty and duringpregnancy; and

(2) compensatory hyperplasia, that is,hyperplasia that occurs when a portion of thetissue is removed or diseased.

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• For example, when a liver is partially resected,mitotic activity in the remaining cells begins as earlyas 12 hours later, eventually restoring the liver to itsnormal weight.

• The stimuli for hyperplasia in this setting are growthfactors produced by remnant hepatocytes in theliver.

• After restoration of the liver mass, cell proliferationis "turned off" by various growth factor inhibitors.

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• Pathologic hyperplasia

• are caused by excessive hormonal or growth factorstimulation.

• For example, after a normal menstrual period thereis a burst of uterine epithelial proliferation that isnormally tightly regulated by stimulation throughpituitary hormones and ovarian estrogen and byinhibition through progesterone .

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• However, if the balance between estrogenand progesterone is disturbed, endometrialhyperplasia ensues, a common cause ofabnormal menstrual bleeding.

• Hyperplasia is also an important response ofconnective tissue cells in wound healing, inwhich proliferating fibroblasts and bloodvessels aid in repair.

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• It is important to note that in all these situations,the hyperplastic process remains controlled; ifhormonal or growth factor stimulation abates, thehyperplasia disappears.

• It is this sensitivity to normal regulatory controlmechanisms that distinguishes benign pathologichyperplasia from cancer, in which the growth controlmechanisms become dysregulated or ineffective.

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• However, pathologic hyperplasia constitutesa fertile soil in which cancerous proliferationmay eventually arise.

• Thus, patients with hyperplasia of theendometrium are at increased risk ofdeveloping endometrial cancer.

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Atrophy

• Shrinkage in the size of the cell by the loss of cellsubstance is known as atrophy.

• When a sufficient number of cells is involved, theentire tissue or organ diminishes in size, becomingatrophic.

• It should be emphasized that although atrophiccells may have diminished function, they are notdead.

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Causes of atrophy include

1. decreased workload (e.g., immobilization ofa limb to permit healing of a fracture),

2. loss of innervation,

3. diminished blood supply,

4. inadequate nutrition,

5. loss of endocrine stimulation.

6. aging (senile atrophy).

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• Although some of these stimuli are physiologic (e.g.,the loss of hormone stimulation in menopause) andothers pathologic (e.g., denervation), thefundamental cellular changes are identical.

• The cell turns to a smaller size at which survival isstill possible; a new equilibrium is achieved betweencell size and diminished blood supply, nutrition.

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• Atrophy results from decreased protein synthesisand increased protein degradation in cells.

• Protein synthesis decreases because of reducedmetabolic activity.

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Metaplasia

• Is a reversible change in which one adult cell type(epithelial or mesenchymal) is replaced by anotheradult cell type.

• In this type of cellular adaptation, cells sensitive to aparticular stress are replaced by other cell typesbetter able to withstand the adverse environment.

• Metaplasia is thought to arise by genetic"reprogramming" of stem cells.

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• Epithelial metaplasia is exemplified by thesquamous change that occurs in therespiratory epithelium in habitual cigarettesmokers.

• The normal ciliated columnar epithelial cellsof the trachea and bronchi are focally orwidely replaced by stratified squamousepithelial cells.

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• Although the metaplastic squamous epithelium hassurvival advantages, important protectivemechanisms are lost, such as mucus secretion andciliary clearance of particulate matter.

• Moreover, the influences that induce metaplastictransformation, if persistent, may predispose tomalignant transformation of the epithelium.

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In fact, in a common form of lung cancer, squamousmetaplasia of the respiratory epithelium oftencoexists with cancers composed of malignantsquamous cells.

It is thought that cigarette smoking initially causessquamous metaplasia, and cancers arise later insome of these altered foci.

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Metaplasia need not always occur in thedirection of columnar to squamousepithelium; in chronic gastric reflux, thenormal stratified squamous epithelium ofthe lower esophagus may undergometaplastic transformation to gastric-typecolumnar epithelium (Barret’s esophagus).

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Photomicrograph of the trachea from a smoker. Note that the columnar ciliated epithelium has been replaced by squamous epithelium.

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Summary

• Cellular adaptations include:

1. Hyperplasia (more cells)

2. Hypertrophy (bigger cells)

3. Atrophy (smaller cells)

4. Metaplasia (different type of cells)

• Adaptations could be physiologic or pathologic.

• Adaptations are reversible if the causative stimulus is removed.

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Speech is silver but silence is gold

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