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Molecular and Cellular Basis of
Disease (MCBD)
Cell Injury
Normal
cell
+ Stress
- Stress
Adapted
Cell
Injury
Reversibly
injured cell
Irreversibly
Injured cell
Apoptosis
Dead cell
Necrosis
Overview
Normal
cell
+ Stress
- Stress
Adapted
Cell
Cellular adaptation
Normal
cell
+Stress
- Stress
Adapted
Cell
Stress = ?
Increased/decreased workload
* skeletal muscle and body building
* cardiac muscle and hypertension
* skeletal muscle disuse (limb immobilization)
Increased/decreased stimulation
* estrogenic stimulation of uterus in pregnancy
* estrogen/prolactin stimulation of breast (lactation)
* denervation of muscle
Adapted
Cell
Cellular adaptations to stress
1. Hyperplasia (more cells)
2. Hypertrophy (bigger cells)
3. Atrophy (smaller cells)
4. Metaplasia (different type of cells)
1. Hyperplasia
(more cells)
1. Physiologic
* Hormonal (breast/uterus in pregnancy)
* Compensatory (liver after partial hepatectomy)
2. Pathologic
Excessive hormone/GF stimulation of target tissue
* Endometrial hyperplasia (x’s estrogen)
* Benign prostatic hyperplasia (x’s androgens)
* Connective tissue cells in wound healing
Thyroid hyperplasia
Hyperplasia
(Mechanism)
Cell proliferation
via increased production of
TRANSCRIPTION FACTORS
due to
* Increased production of GF
* Increased levels of GF receptors
* Activation of intracellular signaling
Results in larger organ
Adapted
Cell
2. Hypertrophy (larger cells)
* Not due to swelling
* Increased synthesis of structural components
* Results in larger organ
* May occur with hyperplasia
Hypertrophy
Comments
* Often involves switch from adult to fetal/neonatal
forms i.e. a-myosin heavy chain  b-myosin
heavy chain
* Limited (can only increase so much)
Hypertrophy (Heart)
Hypertrophy of uterus
Normal
Hypertrophied
Cardiac smooth muscle hypertrophy
Hypertrophy
(Mechanisms)
•Increased synthesis of structural proteins via
•Transcription factors (i. e. c-fos and c-jun)
•Growth factors (TGF-b, IGF-1, FGF)
•Vasoactive agents (endothelien-1, AII)
Figure 1-4 Changes in the expression of selected
genes and proteins during myocardial hypertrophy.
3. Atrophy
(smaller cells)
1. Physiologic
During development: i.e. notochord; thyroglossal duct
2. Pathologic (local or generalized) via
* disuse
* Loss of endocrine stimulation
* denervation
* Aging
* ischemia
* Pressure
* Nutrition
Normal
Atrophied
Brain atrophy
Muscle fiber atrophy. The number of cells is the same as before
the atrophy occurred, but the size of some fibers is reduced.
This is a response to injury by "downsizing" to conserve the
cell. In this case, innervation of the small fibers in the center
was lost. This is a trichrome stain.
Atrophy
(Mechanism)
Reduction in structural components
Decreased number of mito, myofilaments, ER via
proteolysis (lysosomal proteases; ubiquitin-proteosome
system)
Increase in number of autophagic vacuoles
Residual bodies (i.e. lipofuscin  brown atrophy)
NB: diminished function but not dead
4. Metaplasia
**One adult cell type replaces another**
Reversible
Columnar to squamous epithelium (most common epithelial
type of metaplasia)
Chronic irritation i.e. (in trachea and bronchi of smokers)
Vit A deficiency squamous metaplasia in respiratory
epithelium
May be some loss of function
May predispose to maligancy
Photomicrograph of the trachea from a smoker. Note that the columnar
ciliated epithelium has been replaced by squamous epithelium.
Photomicrograph of the junction of normal epithelium (1) with hyperplastic
transitional epithelium (2).
Metaplasia
(Mechanism)
Reprogramming
1. of stem cells present in normal tissues
2. of undifferentiated mesenchymal cells
in connective tissue
Mediated by signals from
cytokines, GF or ECM
Leading to induction of specific transcription
factors
Metaplasia versus Dysplasia
1. Dysplasia is a pathological term used to refer to an
irregularity that hinders cell maturation within a particular
tissue whereas Metaplasia is the process of the reversible
substitution of a distinct kind of cell with another mature
cell of the similar distinct kind.
2. Dysplasia is cancerous whereas Metaplasia is noncancerous.
3. Metaplasia can be stopped by removing the abnormal
stimulus, but Dysplasia is a non-reversible process.