CH1 - Growth Adaptations, Cellular Injury, and Cell Death Flashcards
What are the basic principles of growth adapdations?
An organ is in homeostasis with the physiologic stress placed on it. An increase, decrease, or change in stress on an organ can result in growth adaptations.
What leads to an increase in organ size?
An increase in stress
Hypertrophy occurs via what?
an increase in the size
Hyperplasia occurs via what?
an increase in the number of cells
What does hypertrophy involve?
gene activation, protein synthesis, and production of organelles.
What does Hyperplasia involve?
the production of new cells from stem cells.
Permanent tissues are… Do they undergo hypertrophy or hyperplasia?
cardiac muscle, skeletal muscle, and nerve, cannot make new cells and undergo hypertrophy only.
Pathologic hyperplasia leads to what?
(e.g., endometrial hyperplasia) can progress to dysplasia and,eventually cancer.
What is an exception to pathologic hyperplasia leading to cancer?
benign prostatic hyperplasia (BPH), which does notincrease the risk for prostate cancer,
What leads to a decrease in organ size?
A decrease in stress (e.g., decreased hormonal stimulation, disuse, or decreased nutrients/blood supply) (atrophy).
Atrophy occurs via?
a decrease in the size and number of cells
How does a decrease in cell number occur?
via apoptosis.
Decrease in cell size occurs via what?
ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components.
What happens in ubiquitin-proteosome degradation?
intermediate filaments of the cytoskeleton are tagged with ubiquitin and destroyed by proteosomes.
What does autophagy of cellular components involve?
generation of autophagic vacuoles that fuse with lysosomes whose hydrolytic enzymes breakdown cellular components.
What happens in METAPLASIA?
change in stress on an organ leads to a change in cell type
Metaplasia most commonly involves?
change of one type of surface epithelium (squamous, columnar, or urothelial) to another
How do metaplastic cells handle the new stress?
they are better able to handle the new stress.
Esophagus is normally lined by what?
nonkeratinizing squamous epithelium (suited to handle friction of a food bolus)
Barrett esophagus
Acid reflux from the stomach causes metaplasia to nonciliated mucin-producing columnar cells (better able to handle the stress of acid
Metaplasia occurs via what?
programming of stem cells, which then produce the new cell type.
Is Metaplasia reversible?
with removal of the driving stressor.
Can metaplasia progress to cancer?
Under persistent stress, can progress to dysplasia and eventually result in cancer.
What is an exception to metaplasia leading to cancer?
apocrine metaplasia of breast, which carries no increased risk for cancer.
Vitamin A deficiency can result in what?
metaplasia,
Vitamin A is necessary for what?
differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye.
Keratomalacia
In vitamin A deficiency, the thin squamous lining of the conjunctiva undergoes metaplasia into stratified keratinizing squamous epithelium.
Myositis Ossificans
Mesenchymal (connective) tissues can undergo metaplasia. A classic example is myositis ossificans in which muscle tissue changes to bone during healing after trauma
DYSPLASIA is?
Disordered cellular growth
Dysplasia most often refers to?
proliferation of precancerous cells
Cervical intraepithelial neoplasia (CIN)
represents dysplasia and is a precursor to cervical cancer
Dysplasia often arises from?
longstanding pathologic hyperplasia (e.g., endometrial hyperplasia) or metaplasia (e.g., Barrett esophagus)
Is dysplasia is reversible?
yes, with alleviation of inciting stress.
In dysplasia what happens if stress persists?
dysplasia progresses to carcinoma irreversible)
What is aplasia?
it is failure of cell production during embryogenesis (e.g., unilateral renal agenesis)
What is hypoplasia?
it is a decrease in cell production during embryogenesis, resulting in a relatively small organ (e.g., streak ovary in Turner syndrome)
When does cellular injury occur?
when a stress exceeds the cells ability to adapt
The likelihood of injury depends on what?
the type of stress, its severity, and the type of cell affected.
What are highly susceptible to ischemic injury? As opposed to?
neurons whereas, skeletal muscle is relatively more resistant.
Slowly developing ischemia
eg: renal artery atherosclerosis, results in ATROPHY
acute ischemia
eg: renal artery embolus, results in INJURY
What are common causes of cellular injury?
inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations.
What is HYPOXIA?
Low oxygen delivery to tissue; important cause of cellular injury
What is the final electron acceptor in the electron transport chain of oxidative phosphorylation?
Oxygen
Decreased oxygen results in what?
impairs oxidative phosphorylation, resulting in decreased ATP production
What does a lack of ATP leads to?
cellular injury
What are some causes of hypoxia?
include ischemia, hypoxemia, and decreased 02 - carrying capacity of blood.
Ischemia is?
decreased blood flow through an organ
Ischemia arises with?
- Decreased arterial perfusion (eg atherosclerosis) 2. Decreased venous drainage (eg Budd-Chiari syndrome) 3. Shock?generalized hypotension resulting in poor tissue perfusion
Hypoxemia is?
a low partial pressure of oxygen in the blood (Pao2< 60 mm Hg, SaO2<90%).
Hypoxemia arises with
- High altitude 2. Hypoventilation 3. Diffusion defect 4. V/Q mismatch
High altitude to hypoxemia, how?
Decreased barometric pressure results in decreased PaO2
Hypoventilation to hypoxemia, how?
Increased Paco, results in decreased PaO2
Diffusion defect to hypoxemia, how?
PAO2 not able to push as much O2 into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis)
V/Q mismatch to hypoxemia, how?
Blood bypasses oxygenated lung (circulation problem, eg: right-to-left shunt), or oxygenated air cannot reach blood (ventilation problem, eg: atelectasis)
Decreased O2-carrying capacity arises with what?
hemoglobin (Hb) loss or dysfunction
What are some examples of Decreased O2-carrying capacity?
- Anemia 2. Carbon monoxide poisoning 3. Methemoglobinemia
Anemia leading to decreased O2 carrying capacity.
(decrease in RBC mass) PaO2 normal; SaO2 normal
Carbon monoxide poisoning
CO binds hemoglobin more avidly than oxygen
What is the PaO2 and SaO2 for carbon monoxide poisoning?
PaO2 normal; SaO2 decreased
Exposures for Carbon monoxide poisoning
include smoke from fires and exhaust from cars or gas heaters.
Classic finding for Carbon monoxide poisoning
cherry-red appearance of skin.
Early sign of exposure for Carbon monoxide poisoning
headache; significant exposure leads to coma and death.
What is Methemoglobinemia?
Iron in heme is oxidized to Fe3+ which cannot bind oxygen
PaO2 and SaO2 for Methemoglobinemia?
PaO2 normal; SaO2 decreased
Methemoglobinemia is Seen with?
oxidant stress (eg sulfa and nitrate drugs) or in newborns