1. Adaptation to cell injuries
Dr. Mamlook Elmagraby

2. Objectives of the lecture:
Upon completion of this lecture, students should be able to:
Understands the concept of cells and tissue adaptation to environmental stress including the meaning and clinical manifestations of:
Aplasia
Hypoplasia
Atrophy,
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia

3. Consequences of cellular Injury

4. Adaptation to cell injuries
Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment Physiologic adaptations usually represent responses of cells to normal stimulation by hormones or to the demands of mechanical stress Pathologic adaptations are responses to stress that allow cells to modulate their structure and function and thus escape injury, but at the expense of normal function Adaptive changes are, for the most part, reversible on discontinuation of the stress Mammalian cells adapt to injury by conserving resources (decreasing or ceasing differentiated functions and focusing exclusively on their own survival)

5. Adaptation to cell injuries
If an injury exceeds the adaptive capacity of the cell, the cell dies
The major adaptive responses are:
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
Intracellular storage of certain endogenous or exogenous materials

6. Atrophy Physiologic atrophy
Atrophy is reduced size of an organ or tissue resulting from a decrease in cell size and number
Physiologic atrophy
During normal development: thyroglossal duct
The uterus after parturition

7. Atrophy Pathologic atrophy Decreased workload (atrophy of disuse)
Damage to the nerves
Diminished blood supply
Inadequate nutrition
Loss of endocrine stimulation
Pressure

8. Kidneys, normal (left) and ischemic atrophy (right) - Gross, cut surfaces
These kidneys are from a patient who had atherosclerotic stenosis of one renal artery,
leading to a compensatory decrease in size (atrophy) of one kidney.
The atrophy primarily involves the cortex, which contains the most metabolically active cells

9. Atrophy Mechanisms of Atrophy:
Protein synthesis decreases because of reduced metabolic activity
Atrophy results from increased protein degradation in cells: activation of ubiquitin ligases
Increased autophagy (the process in which the starved cell eats its own components in an attempt to find nutrients and survive)

10. Hypertrophy
Hypertrophy is an increase in the size of cells, resulting in an increase in the size of the organ
Hypertrophy occurs in organs having nondividing cells
Hypertrophy and hyperplasia may coexist
The increased size of the cells is due to the synthesis of more cellular structural components

11. Hypertrophy The stimuluses for hypertrophy include:
Increased workload
Hormone or growth factor-induced increase in the size of an organ
Types of hypertrophy:
Physiologic hypertrophy:
pregnant uterus
Pathologic hypertrophy :
Heart hypertrophy resulting from chronic hemodynamic overload

12. Physiologic hypertrophy of the uterus during pregnancy.
A, Gross appearance of a normal uterus (right) and a gravid uterus (removed for postpartum bleeding) (left).
B, Small spindle-shaped uterine smooth muscle cells from a normal uterus (left) compared with large plump cells in gravid uterus (right)

13. Hearts, hypertrophied, normal (middle)
The heart on the left has undergone hypertrophy (increase in cell size resulting in thickened myocardium) due to increased workload (adaptation).

14. Hyperplasia
Hyperplasia is an increase in the number of cells in an organ or tissue, usually resulting in increased mass of the organ or tissue
It occurs in organs having dividing cells
The hyperplasia regresses if the stimulation is eliminated
Prognosis:
Sometimes, increased risk for developing cancer

15. Hyperplasia Physiologic Hyperplasia Pathologic Hyperplasia
Hormonal hyperplasia: proliferation of the female breast
Compensatory hyperplasia: regeneration of the liver
Pathologic Hyperplasia
Excesses of hormones :
Endometrial hyperplasia
Benign prostatic hyperplasia
Growth factors produced by viral genes or by infected cells may stimulate cellular proliferation

16. Hyperplasia Mechanisms of Hyperplasia
Hyperplasia is the result of growth factor–driven proliferation of mature cells
If the proliferative capacity of the mature cells is compromised, stem cells can regenerate

17. Thyroid gland, normal - Gross
The two lobes of the thyroid gland lie on either side of the larynx and upper trachea. The lobes are connected by the isthmus.
Thyroid gland, diffuse hyperplasia of Graves disease - Gross
The gland is uniformly but not markedly enlarged.
Thyroid gland, normal
The thyroid follicles have a single layer of low cuboidal epithelium surrounding a central collection of colloid.
Thyroid gland, hypertrophy and hyperplasia
In contrast to the above image, the epithelial cells here are tall columnar (hypertrophy). The cells have also proliferated (hyperplasia), causing them to become crowded. Consequent buckling into the follicle lumens has formed papillary projections

18. Metaplasia
Metaplasia is a change in which one differentiated cell type is replaced by another differentiated cell type
Substitution of cells that are sensitive to stress by cell types better able to tolerate the hostile environment
Prognosis:
Reversible change
Loss of function
Malignant transformation in metaplastic tissue

19. Metaplasia Examples include: Epithelial metaplasia
In the respiratory tract, the normal ciliated columnar epithelial cells are often replaced by stratified squamous epithelial cells
Barrett esophagus
Connective tissue metaplasia
Bone formation in muscle (myositis ossificans)

20. Schematic diagram of columnar to squamous metaplasia

22. Metaplastic transformation of esophageal stratified squamous epithelium (left) to mature columnar epithelium (so-called Barrett metaplasia).

24. Metaplasia Mechanisms of Metaplasia: Reprogramming of stem cells
The change in differentiation is brought about by cytokines, growth factors, and extracellular matrix components
These external stimuli alter the activity of transcription factors that regulate differentiation
The activity of transcription factors promote the expression of genes that drive cells toward a specific differentiation pathway

25. Dysplasia
Dysplasia means disordered cellular proliferation and maturation Dysplasia is the morphologic expression of a molecular disturbance in growth regulation Dysplastic cells are very similar to cancer cells but they have NOT yet acquired the ability to invade into tissue or metastasize Unlike cancer cells, dysplastic cells are NOT autonomous, and with intervention, tissue appearance may still revert to normal Dysplasia often occurs in hyperplastic and metaplastic epithelium

26. Dysplasia Dysplastic cells usually show:
A loss of the cellular uniformity (pleomorphism)
Large hyperchromatic nuclei with a high nucleo-cytoplasmic ratio
Mitotic figures are abundant and appear in abnormal locations
A loss of the architectural orientation

27. This field shows the junction of normal colonic mucosa and the mucosa of the adenomatous polyp.
Note that the normal mucosa shows evidence of normal differentiation because the cells have clear vacuoles containing mucin.
By contrast, the epithelial cells of the polyp have lost the specialized function of mucin production.

28. Dysplasia
Prognosis:
Severe epithelial dysplasia frequently occurs before the appearance of cancer
Dysplasia does NOT necessarily progress to cancer
Mild to moderate changes that do not involve the entire thickness of epithelium may be reversible

29. Aplasia Hypoplasia Aplasia is a failure of cell production
During fetal development, aplasia results in agenesis, or absence of an organ due to failure of cell production
Later in life, it can be caused by permanent loss of precursor cells in proliferative tissues, such as the bone marrow
Hypoplasia
Hypoplasia is a decrease in cell production that is less extreme than in aplasia
Hypoplasia is seen in the partial lack of growth and maturation of gonadal structures in Turner syndrome and Klinefelter syndrome