1. Cellular Adaptations Al-Quds University
Dr. Marwan Qubaja / Pathology I
Cellular Adaptations
Al-Quds University
Assistant professor of pathology.
Faculty of Medicine
Pathology Department

2. Cellular Adaptation to Injury
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Cellular Adaptation to Injury
A new steady state which lies between normal unstressed cell, and the injured overstressed cell, in which the cell can function and preserve viability.

3. Cellular Adaptation 1) Physiological adaptation
Cellular Adaptations
Cellular Adaptation
Dr. Marwan Qubaja / Pathology I
1) Physiological adaptation
responses of cells to normal stimulation by hormones or endogenous chemical mediators
e.g. hormones leading to enlargement of the breast and the uterus during pregnancy
2) Pathological adaptation
allows the cells to modulate their environment and ideally escape injury
e.g. hormones produced by tumors leading to endometrial hyperplasia

4. Mechanisms of Cellular Adaptation
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Mechanisms of Cellular Adaptation
up- or down-regulation of specific cellular receptors
receptor binding
Increase or decrease of protein synthesis
switch from producing one type of protein to another
Cellular adaptation can proceed by a number of mechanisms. Some adaptive responses involve up- or down-regulation of specific cellular receptors; for example, cell surface receptors involved in the uptake of low-density lipoproteins (LDLs) are normally down-regulated when the cells are cholesterol replete (Chapter 7). Other adaptive responses are associated with the induction of new protein synthesis by the target cell. These proteins, for example heat shock proteins, may protect cells from certain forms of injury. Still other adaptations involve a switch from producing one type of protein to another, or marked overproduction of a specific protein; such is the case in cells synthesizing various collagens and extracellular matrix proteins in chronic inflammation and fibrosis (Chapter 3). Cellular adaptive responses can thus occur at any of a number of steps, including receptor binding; signal transduction; or protein transcription, translation, or export. In this section, the adaptive changes in cell growth and differentiation that are particularly important in pathologic conditions are considered. These include atrophy (decrease in cell size), hypertrophy (increase in cell size), hyperplasia (increase in cell number), and metaplasia (change in cell type).

5. Cellular adaptation Types of adaptive responses:
Cellular Adaptations
Cellular adaptation
Dr. Marwan Qubaja / Pathology I
Types of adaptive responses:
Atrophy - decrease in cell size
Hypertrophy - increase in cell size
Hyperplasia - increase in cell number
Metaplasia - change in cell type
 Others: aplasia, hypoplasia

6. Cellular Adaptation to stress normal bronchial epithelial cell
Cellular Adaptations
Cellular Adaptation to stress
Dr. Marwan Qubaja / Pathology I
normal bronchial epithelial cell
adaptation
cell injury
atrophy
hypertrophy
hyperplasia
metaplasia
dysplasia
reversible
irreversible
necrosis

7. Cellular Adaptations
Atrophy
Dr. Marwan Qubaja / Pathology I
Shrinkage in the size of the cell by loss of cell substances, leading to diminished function of the cell and a new equilibrium is reached.
Accompanied by decrease in the organ size, if sufficient number of cells is involved.
The cells are not dead

8. Causes of Atrophy 1) Physiological: 2) Pathological:
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Causes of Atrophy
1) Physiological:
thymic involution, aging
loss of hormonal stimuli (menopause)
2) Pathological:
decrease work load (immobilization of a limb to permit healing of a fracture)
loss of innervation (Denervation atrophy)
diminished blood supply (ischemic atrophy)
inadequate nutrition

9. Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
A, Atrophy of the brain in an 82-year-old male with atherosclerotic disease. Atrophy of the brain is due to aging and reduced blood supply. The meninges have been stripped. B, Normal brain of a 25-yr-old male. Note that loss of brain substance narrows the gyri and widens the sulci

10. Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Normal
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.
These kidneys are from a patient who had atherosclerotic stenosis of one renal artery

11. Cellular Adaptations
Mechanisms of Atrophy
Dr. Marwan Qubaja / Pathology I
Imbalance between protein synthesis and degradation is the fundamental step, leading to reduction in structural components.
Decreased synthesis, increased catabolism, or both
the fundamental cellular changes are identical in physiological and pathological causes.
Sometimes the number of cells can be reduced by the process apoptosis

12. Atrophy: increase catabolism
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Proteolytic systems for degradation:
1) Lysosomes contain hydrolases and other enzymes
degrade exogenous proteins engulfed by endocytosis
degrade subcellular components (e.g. organelles) leading to the formation of autophagic vacuoles
In many situations, atrophy is accompanied by marked increases in the number of autophagic vacuoles, a fusion of lysosomes with intracellular organelles and cytosol that allows the catabolism and turnover of self-components in a given cell. Some of the cell debris within the autophagic vacuole may resist digestion and persist as membrane-bound residual bodies (e.g., lipofuscin), described in greater detail later (see p 20).

13. Ubiquitin: An abundant protein found in normal cells.
2) The ubiquitin-proteasome pathway:
Degradation of cytosolic and nuclear proteins
Responsible for the accelerated proteolysis in hypercatabolic
states (e.g. cancer)
The protein/ubiquitin complexes are engulfed by the cytoplasmic
proteasome
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Ubiquitin:
An abundant protein found in normal cells.
It has a role in removing old or damaged proteins by acting as a cofactor for proteolysis.
Proteasomes: non lysosomal proteinases.

14. The ubiquitin-proteasome pathway:
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
The ubiquitin-proteasome pathway:

15. Cellular Adaptations
Hypertrophy
Dr. Marwan Qubaja / Pathology I
Increase in the size of cells by an increase in the number and density of the cellular substances, leading to an over all increase in the size and the function of the organ, and a new equilibrium is reached.
Mainly occurs in organs composed of cells that can’t divide (cardiac & skeletal muscles).
NO NEW CELLS, JUST BIGGER CELLS

16. Causes of Hypertrophy:
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Causes of Hypertrophy:
Physiological or pathological:
Increase in functional demand or work load e.g. body building, hypertension, aortic valve disease
Increase in hormonal stimulation. This involves both hypertrophy and hyperplasia and both result in an enlarged (hypertrophic) organ.
e.g. the gravid uterus occurs as a consequence of estrogen stimulation of both smooth muscle hypertrophy and smooth muscle hyperplasia

17. Mechanisms of Hypertrophy
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Mechanisms of Hypertrophy
an increased synthesis of structural proteins and organelles leading to an overall increase in the workload of the organ.

18. hypertrophy after myocardial infarction
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I .
The mechanisms of cardiac hypertrophy:
mechanical triggers, such as stretch
trophic triggers, such as activation of α-adrenergic receptors

19. Hypertrophy in hypertension
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Hypertrophy in hypertension
Adaptive changes may not be completely benign; they can also result in a dramatic change in the cellular phenotype:
Reactivation of certain genes.
Switch of contractile proteins to a different type.
Degenerative changes overtime leading to failure of organ
The mechanisms driving cardiac hypertrophy involve at least two types of signals: mechanical triggers, such as stretch, and trophic triggers, such as activation of α-adrenergic receptors. Whatever the exact mechanism or mechanisms of hypertrophy, a limit is reached beyond which the enlargement of muscle mass can no longer compensate for the increased burden; in the case of the heart, cardiac failure ensues

20. Skeletal muscle hypertrophy in body building:
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Skeletal muscle hypertrophy in body building:
At this stage, a number of "degenerative" changes occur in the myocardial fibers, of which the most important are fragmentation and loss of myofibrillar contractile elements. The factors that limit continued hypertrophy and cause the regressive changes are incompletely understood. There may be finite limits of the vasculature to adequately supply the enlarged fibers, of the mitochondria to supply ATP, or of the biosynthetic machinery to provide the contractile proteins or other cytoskeletal elements.

21. Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Hyperplasia
an increase in the size of the organ due to increase in the number of the cells in the organ, leading to increase in the function.
SEEN IN CELLS THAT CAN DIVIDE

22. Hyperplasia Gravid uterus
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Hyperplasia
Gravid uterus

23. Causes of Hyperplasia:
Cellular Adaptations
Causes of Hyperplasia:
Dr. Marwan Qubaja / Pathology I
Physiological:
hormonal hyperplasia (e.g. female breast at puberty and during pregnancy)
compensatory hyperplasia: occurs when a portion of the tissue is removed or diseased which is under the influence of growth factors (e.g. liver resection, wound healing)
Pathological:
Under the effect of hormones or growth factors. (e.g. Endometrial hyperplasia, skin wart)
exemplified by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy; and (2) compensatory hyperplasia, that is, hyperplasia that occurs when a portion of the tissue is removed or diseased. For example, when a liver is partially resected, mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver to its normal weight. The stimuli for hyperplasia in this setting are polypeptide growth factors, produced by remnant hepatocytes as well as nonparenchymal cells found in the liver. After restoration of the liver mass, cell proliferation is "turned off" by various growth inhibitors. Hyperplasia is also a critical response of connective tissue cells in wound healing, by which growth factor-stimulated fibroblasts and blood vessels proliferate to facilitate repair.
forms of pathologic hyperplasia are instances of excessive hormonal or growth factor stimulation. For example, after a normal menstrual period there is a burst of proliferative endometrial activity that is essentially physiologic hyperplasia. This proliferation is normally tightly regulated by stimulation through pituitary hormones and ovarian estrogen and by inhibition through progesterone . However, if the balance between estrogen and progesterone is disturbed, endometrial hyperplasia ensues, a common cause of abnormal menstrual bleeding.
Increased sensitivity to normal levels of growth factors may also underlie pathologic hyperplasia. Thus, the common skin wart is caused by an increased expression of various transcription factors by an infecting papillomavirus; any minor trophic stimulation of the cell by growth factors results in an overexuberant mitotic activity.

24. Cellular Adaptations
Hyperplasia
Dr. Marwan Qubaja / Pathology I
Both hypertrophy and hyperplasia are reversible, if the stimulus is removed.
This differentiates these processes from cancer, in which cells continue to grow despite the absence of hormonal stimuli.
pathologic hyperplasia constitutes a fertile soil in which cancerous proliferation may eventually arise.
e.g. patients with hyperplasia of the endometrium are at increased risk of developing endometrial cancer
e.g. papillomavirus infections predispose to cervical cancers

25. Hypertrophy & hyperplasia Summary
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Hypertrophy & hyperplasia Summary

26. Cellular Adaptations
Metaplasia
Dr. Marwan Qubaja / Pathology I
Replacement of one type of adult cell, whether epithelial or mesenchymal, by another type of adult cell
aiming at replacing cells that are sensitive to certain stimuli by a more resistant cell type.
This happens through reprogramming of stem cells or undifferentiated mesenchymal cells.
the influences that induce metaplastic transformation, if persistent, may induce cancer transformation in the metaplastic epithelium

27. Examples of Metaplasia
Cellular Adaptations
Examples of Metaplasia
Dr. Marwan Qubaja / Pathology I
Epithelial metaplasia is exemplified by the squamous change that occurs in the respiratory epithelium in habitual cigarette smokers. The normal ciliated columnar epithelial cells of the trachea and bronchi are focally or widely replaced by stratified squamous epithelial cells. Vitamin A deficiency may also induce squamous metaplasia in the respiratory epithelium. Presumably, the more "rugged" stratified squamous epithelium is able to survive under circumstances that the more fragile specialized epithelium would not tolerate. Although the adaptive metaplastic epithelium probably has survival advantages, important protective mechanisms are lost, such as mucus secretion and ciliary clearance of particulate matter. Epithelial metaplasia is therefore a double-edged sword; moreover, the influences that induce metaplastic transformation, if persistent, may induce cancer transformation in the metaplastic epithelium. Thus, in a common form of lung cancer, squamous metaplasia of the respiratory epithelium often coexists with cancers composed of malignant squamous cells. Although not proved, it is thought that cigarette smoking initially causes squamous metaplasia, and cancers arise later in some of these altered foci. Metaplasia need not always occur in the direction of columnar to squamous epithelium; in chronic gastric reflux, the normal stratified squamous epithelium of the lower esophagus may undergo metaplastic transformation to gastric or intestine-type columnar epithelium (Fig. 1-10). Metaplasia may also occur in mesenchymal cells but less clearly as an adaptive response. Thus, bone or cartilage may form in tissues where they are normally not encountered. For example, bone is occasionally formed in soft tissues, particularly (but not always) in foci of injury.
(respiratory epithelium)

28. epithelium (so-called Barrett metaplasia)
Cellular Adaptations
Dr. Marwan Qubaja / Pathology I
Metaplastic transformation of esophageal stratified squamous epithelium (left) to mature columnar
epithelium (so-called Barrett metaplasia)