Pathophysiology of Cellular Adaptations & Disturbance of Growth

Dr. Hemn Hassan OthmanMSc, PhD, PD Pathology

Pharmacology and Toxicology

2019-2020

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Aspects of disease processes are:1. Etiology or the cause of diseases:

It can be either ;

a. Genetic .

b. Acquired.

2. The pathogenesis (mechanism) .

3. Morphological changes.

4. Functional changes (Biochemical)

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Cellular response to stress:

Every cell in the living body is in balance with it’senvironment it is considered to be in ahomeostatic balance or “ steady state” .

There are a variety of systems protect cellintegrity, i.e. cell membrane, phagocytosis,excretion of exogenous chemicals (bile, urine),host defense mechanisms (inflammation, immunesystem), system of repair like (antioxidants, DNA-repair enzymes).2/4/2020 3

If more excessive external stimuli occur, thecell may be able to adapt to the changes, i.e.hypertrophy (increased workload), atrophy(decrease workload).

If the limits of adaptive capability areexceeded, or when the protective systems areoverwhelmed, the cell is "injured".

The injury of the cell may range from mild andfully reversible to severe and lethal (nonreversible).2/4/2020 4

Adaptive responses:

1. Atrophy

2. Hypertrophy

3. Hyperplasia

4. Metaplasia

5. Dysplasia

6. Intracellular & Extracellular storage

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Cellular Adaptations

Size Number Type

Atrophy

1. Disuse.

2. Loss of endocrine stimulation.

3. Denervation.

4. Inadequate nutrition.

5. Ischemia.

Hyperplasia Dysplasia

Intracellular Accumulations

Calcifications

Dystrophic Metastatic

Hypertrophy Metaplasia

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Developmental Errors:

Hypoplasia: Reduce in the number of thecell (Reduction in size), also can be definedas retarded growth. The structure still canbe recognized.

Aplasia: Retarded in growth, organ massexist but no structure.

Agenesis: There is no sign of organ.

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Aplasia cutis congenita

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1. Atrophy:

(1) Definition: Acquired loss of size due toreduction of cell size or number ofparenchyma cells in an organ.

(2) Types:

Physiologic: i. e. Aging; shrinkingmammary gland after lactation; theuterus after delivery.

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• Diminished blood supply.

• Loss of nerve stimulus.

• Loss of endocrine stimulation.

• Inadequate nutrition.

• Pressure.

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ATROPHY:shrinkage of cells

Physiologic

Atrophy

Pathologic

Loss of endocrine stimulation

Disuse Denervation Inadequate nutrition

Ischemia

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Atrophy:

represents a reduction in the structuralcomponents of the cell. The cell containsfewer mitochondria, myofilaments, alesser amount of endoplasmic reticulum,and increasing in the number ofautophagy vacuoles.

Although atrophic cells may havediminished function, they are not dead.

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Left Normal Right Atrophy

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Myocardial Atrophy

Atrophy of the brain

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Atrophy associatedwith Alzheimer’s

Disease

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Loss of endocrine stimulation

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Denervation Atrophy

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Atrophy associatedwith Malnutrition

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Kidneys, normal (left) and ischemic atrophy (right)

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2. HYPERTROPHY:

Increase in the size of cells which results in enlargement of the organs

Mostly seen in cells that cannot divide, i.e.,

Skeletal muscle (strength training)

Cardiac muscle (hypertension)

Changes usually revert to normal if the stimulus is removed

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Types:

• Physiologic: i. e. the physiologic growthof the uterus during pregnancy involvesboth hypertrophy and hyperplasia whichstimulated by estrogenic hormonesthrough smooth muscle estrogenreceptors.

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• Pathologic:

• causes:Increased workload, hormonalstimulation and growth factorsstimulation.

i.e. hypertrophy of heart the most commonstimulus is chronic hemodynamicoverload, due either to hypertension or tofaulty valves.

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Tissue

Epithelial Connective

Loose Connective Tissues

Dense Connective Tissues

MuscleNerve

Connective Tissue Proper

Cartilage

Areolar

Bone Blood

Skeletal Cardiac Smooth

Adipose Reticular Dense regular

Dense Irregular

Elastic

None

Poor

Moderate

Good

Regenerating Capability

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Physiologic

Hypertrophy

Pathologic

Exercise Adaptive Compensatory

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Left Normal heart

center Hypertrophied heart

Right Hypertrophied and dilated heart 2/4/2020 29

Physiologic hypertrophy of the uterus duringpregnancy. A, gross appearance of a normal uterus(right) and a gravid uterus (left) that was removed forpostpartum bleeding,

Normal uterus gravid uterus

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Physiological Hypertrophy due to increase workout

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3. Hyperplasia:

(1) Definition: An increase in the number ofcells in an organ or tissue, which may thenhave increased volume.

(2) Types:

• Physiologic: Response to need, e. g.hyperplasia of the female breast epitheliumat puberty or in pregnancy.

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• Compensatory: Response to deficiency, e. g.Hyperplasia following surgical removal of part ofliver or of one kidney; hyperplasia of the bonemarrow in anemia.

• Excessive stimulation:

Pathologic: as in ovarian tumor producing estrogenand stimulating endometrial hyperplasia;pancreatic islet hyperplasia in infants of a diabeticmother (stimulated by high glucose level).

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• Failure of regulation:Pathologic, as in hyperthyroidism or as in hyperparathyroidism.

• Hyperplasia is also an important response of connective tissue cells in wound healing, in which proliferating fibroblasts and blood vessels aid in repair.

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Tissue

Epithelial Connective

Loose Connective Tissues

Dense Connective Tissues

MuscleNerve

Connective Tissue Proper

Cartilage

Areolar

Bone Blood

Skeletal Cardiac Smooth

Adipose Reticular Dense regular

Dense Irregular

Elastic

None

Poor

Moderate

Good

Regenerating Capability

X

X X

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Left Normal breast Right Hyperplasia

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Thyroid gland, diffuse hyperplasia of Graves disease Thyroid gland, normal

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Thyroid gland, diffuse hyperplasia of Graves disease

Thyroid gland, normal

4. Metaplasia:

(1) Definition: Metaplasia is a reversible change inwhich one adult cell type is replaced by anotheradult cell type.

(2) Causes:

• Changes in environment: i. e. stones in excretoryducts of salivary gland, pancreas, or bile duct leadto change from columnar epithelium to stratifiedsquamous epithelium.

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Schematic diagram of columnar to squamous metaplasia

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• Irritation or inflammation: i. e. In thehabitual cigarettes smoker, the normalpseudostrtified columnar ciliatedepithelial cells of the trachea andbronchi are often replaced focally orwidely by stratified squamousepithelial cells.

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Squamous metaplasia in bronchitis

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Metaplasia of Respiratory Epithelium

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Epithelial metaplasia is a two-edged swordand, in most circumstances, represents an undesirable change.

Moreover, the influences that predispose to such metaplasia, if persistent, may induce cancer transformation in metaplastic epithelium.

Thus, the common form of cancer in the respiratory tract is composed of squamous cells carcinoma SCC.

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Metaplasia may also occur in mesenchymalcells but less clearly as an adaptiveresponse. i. e. fibrous connective tissuecells may be come transformed toosteoblasts chondroblasts to produce boneor cartilage during callus formation.

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Metaplasia of Esophagus Epithelium

Barrett’s Esophagus

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Metaplasia of Uterine Cervix

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Metaplasia of Uterine Cervix

At Higher Magnification

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5. DYSPLASIA:

Deranged cell growth that results in cellsthat vary in size, shape and organization.

Minor degrees are associated with irritationor inflammation.

Most commonly associated with respiratorytract or uterine cervix.

Potentially reversible.

Often a precursor for cancer.

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Dysplasia Cervix uteri

This is dysplasia. The normal squamous epithelium at the lefttransforms to a disorderly growth pattern at the right. This isfarther down the road toward neoplasia.2/4/2020 52

Normal Dysplasia

A / Organ: Brain of an elderly man.Lesion:The brain as a whole as well as it’s gyri appeardecreased in size as compared with that of a young manDiagnosis: Brain Atrophy

B / Brain of a young man

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Organ: Rt. & Lt. Testicles.

Lesion:The left testis is normal whereas the right one has undergone a markeddecrease in size.

Diagnosis: Testicular atrophy

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Organ:Transverse section throughthe ventricles of a heart.

Lesion:Great thickening of the leftventricular wall due toenlargement of cardiac musclecells.

Diagnosis: Left ventricularhypertrophy

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Organ: Uterus

Lesion: 1. The uterus on the left is normal showing the normal mass of smooth muscle in it’s wall.

2. The uterus on the right shows great increase in size due to increase in both size & number of smooth muscle cells in it’s wall.

Diagnosis: Physiological hypertrophy & hyperplasia of uterine smooth muscle fibers during pregnancy

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