(adaptations, injury and death) · •definition: one adult cell type is replaced by another adult...
TRANSCRIPT
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Cellular responses to stress (Adaptations, injury and death)
(1 of 5)
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What will we discuss today?
1- Introduction to pathology
2- Cellular adaptations
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Pathology
Pathos: Suffering (disease) Logos: Study
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4 aspects of disease are the core of pathology
1- Etiology: = causes/factors (Why?)
2- Pathogenesis: = mechanism (How?)
3- Morphologic changes
4- Clinical manifestations
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Etiology
*Factors (causes) of disease (2 classes):
A- Genetic
B- Acquired
*Diseases:
A- Caused by single causes
or B- Multifactorial
….the majority: multifactorial
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Diseases caused by single causes Multifactorial
Infections Hypertension and DM
Inherited disorders caused by single genes, trisomies,….etc.
Atherosclerosis
…..etc. Cancer
…etc.
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Pathogenesis = Cellular events
..When a disease is caused by a bacterium:
-Etiology: the microorganism
-Pathogenesis: binding to receptors, release of toxins, chemical changes in the cell, cellular damage……etc.
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Morphology = Study of shape (structure or anatomy)
*Anatomy of any thing = its structure (shape)
…So: “Anatomic pathology” studies the structural
(morphological) changes of cells, tissues and organs that occur in
disease
*Morphological changes:
1- Gross (macroscopic): what we see by naked eyes when we
look to a tissue or organ
2- Microscopic: what we see by the microscope (tissues and cells)
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Morphology
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Clinical manifestations
The net result
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Disease starts at the level of cell structure and function
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General pathology--Systemic pathology General Systemic (by organ systems)
Cellular responses to stress Cardiovascular system
Inflammation and repair Hematolymphoid system
Hemodynamic disorders Head and neck
Genetic disorders Lung and mediastinum
Diseases of the immune system Gastrointestinal tract and related structures
Neoplasia Urinary tract
Infectious diseases Male reproductive system
Environmental and nutritional diseases Female reproductive system
Diseases of infancy and childhood Breast
Skin, soft tissues, bones and joints
Nervous system
Endocrine system
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Cellular Adaptations
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Before we talk about cellular adaptations:
• Homeostasis: The steady state of cell structure and function (narrow range of changes in cell function according to external and internal environments)
• In homeostasis: -Supplies: Available
-Injurious (noxious) agents: Absent
• Stress = demands (physiologic or pathologic), attack by noxious (injurious) factors, or abnormal DNA
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Before we talk about cellular adaptations: Stress
*Homeostasis Adaptations (new state of homeostasis)…always reversible
*If the stress is more severe Cell injury Reversible injury
More
severe
Irreversible injury Cell death Necrosis
Apoptosis
These are the cellular responses
to stress (in general)
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Cellular adaptations
1- Hypertrophy
2- Hyperplasia
3- Atrophy
4- Metaplasia
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Hypertrophy
cell size, no change in number of cells
*Mechanism: (size + number) of organelles
*May be physiologic or pathologic
*Pathologic: The cause is abnormal
*Physiologic: No abnormal cause
**”Hypertrophy” of any thing = in its size
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Physiologic hypertrophy, an example:
• Skeletal muscle hypertrophy in weight lifters
• Increased workload (physiologic stress)
• Skeletal muscle cells respond to this by
increasing their size not number because they
have limited capacity to divide
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• What is this organ?
• What did happen to it?
• What is the difference between the lower two images?
• What is the name of this condition?
• Did the condition in this example occur alone or with another condition?
• Is this condition physiologic or pathologic?
• What is the cause?
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Pathologic hypertrophy, an example:
*Cardiac myocytes in hypertension
*Increased workload, but the cause
here is pathological (not a physiologic stress)
*Limited capacity to divide
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Some mechanisms in hypertrophy
• Mechanical triggers (e.g., stretch)
• Trophic triggers (e.g., growth factors-hormones)
• Increased proteins, e.g., contractile proteins (myofilaments)
• Switch in protein types synthesized:
- Example: Alpha form of myosin heavy chain is replaced by beta form…slower and more energetically economical contractions
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Hyperplasia
= in number of cells that are capable to divide
*May be physiologic or pathologic
*May occur concurrently with hypertrophy…in this case the stimulus is usually the same
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Physiologic hyperplasia, examples: *Glandular epithelium of the female breast at: -Puberty Hormonal
-Pregnancy
*Compensatory hyperplasia of the liver: After resection of a part of the liver, the remaining cells start to divide as early as 12 hours after
…triggered by growth factors from: -Uninjured hepatocytes
-Non-parenchymal cells
…eventually: normal weight is restored and the hyperplasia is turned off by growth inhibitors
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Pathologic hyperplasia
• Mostly due to in hormones or growth factors, but the increase here is abnormal and not physiologic
• Examples:
*A disease called “Endometrial hyperplasia”:
-It causes abnormal menstrual bleeding (menorrhagia)
-Due to imbalance between estrogen and progesterone
*Blood vessels and fibroblasts in wound healing:
-Growth factors from leukocytes (WBCs) and connective tissue cells
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Pathologic hyperplasia, another example
• Skin warts:
-Etiology: Human papilloma virus (HPV)
-Mechanism: Epithelial hyperplasia due to growth factors
…the GFs are encoded either by viral genes or host cell genes induced by the virus
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*Pathologic hyperplasia may be a precancerous condition, and the best example of this risk is:
Endometrial hyperplasia
Cancer of uterus
(Endometrial adenocarcinoma)
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Atrophy
= Shrinkage ( in cell size)
*Atrophy of any thing = in its size
*Mechanisms:
- metabolic activity
- synthesis (due to decreased metabolism) and degradation of proteins, so the substance of the cell is generally decreased
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Atrophy, some of its causes • Decreased workload…e.g., immobilization of a limb after fracture
• Loss of innervation (pathologic)
• Diminished blood supply
• Inadequate nutrition
• Loss of endocrine stimulation, e.g., menopause (this example is physiologic)
• Aging…called “Senile atrophy” (pathologic)
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Atrophy, more about its mechanisms
• Degradation of proteins is mainly by: ubiquitin-proteasome pathway
-Ubiquitin is a small peptide
-Ubiquitin binds to the cellular protein and targets it for degradation in proteasomes
-Ubiquitin ligase attaches ubiquitin to the protein that will be degraded
**This pathway is also responsible for the accelerated proteolysis seen in cancer cachexia
• Autophagy:
- = Self-eating
- Common in atrophy
- Cell components are isolated in autophagic vacuoles
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Metaplasia
• Definition: One adult cell type is replaced by another adult cell type in response to stress
• Metaplasia occurs in epithelial or mesenchymal cell types…mesenchymal type is generally pathological
• The new type is better in withstanding the new environment
• The stem cells are reprogrammed…not trans-differentiation of already differentiated cells
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• What is the cause of this
condition?
• Is it epithelial or mesenchymal
metaplasia?
• Mention 2 disadvantages of the
condition in this example
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3 more examples of metaplasia
• Columnar-type metaplasia in the lower esophagus due to gastroesophageal reflux disease (GERD)… What is the name of this condition?
• Squamous metaplasia of respiratory epithelium in vitamin A deficiency
…Vitamin A has a role in cell differentiation
• Bone formation in foci of injury (a mesenchymal metaplasia)
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