Cellular Adaptations and Accumulations Flashcards
What are physiologic adaptations?
Responses of cells to normal stimulation by hormones or endogenous chemical mediators
What are pathological adaptations?
Can share same underlying mechanisms as physiologic adaptations; allows cells to modulate their environment and escape injury
True or false: pathological changes to cells can share the same underlying mechanisms as physiologic changes
True
What are the four adaptations that cells can undergo?
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
What is hypertrophy?
Increase in cell size, not number
What is hyperplasia? Metaplasia?
Hyperplasia = Increase in number of cells
Metaplasia = Change in cell type
What is atrophy?
Decrease in cell size
What is the underlying MOA of hypertrophy?
Increase in structural proteins and organelles
True or false: hypertrophy can coexist with hyperplasia
True
Is hypertrophy pathologic or physiologic?
Either
How does hypertrophy signalled? (2)
via hormones or increased functional demand
In the pregnant uterus, which cellular adaptation(s) occur? How is this signalled?
Hypertrophy and hyperplasia via hormonal stimulation
When can pathologic cardiac enlargement occur? (3)
HTN
Aortic valve disease
MI
What happens to non-necrotic cardiomyocytes following MI?
Enlargement of the surrounding the myocytes
What major adaptation (of the four) occurs in a necrotic heart?
Hypertrophy (CANNOT undergo hyperplasia)
What happens to the nucleus during hypertrophy of a cell? Cytoplasm?
Increases in size
Why is a thicker ventricle problematic?
Increased resistance to coronary blood flow
Why do cardiac muscle cell nuclei/cytoplasm increase in hypertrophy (boxcar nuclei)?
Kicking out more proteins
Boxcar nuclei = ?
Increased nuclei size in hypertrophic myocytes
Hypertrophy is the result of what?
increased production of cellular proteins
What are the three types of signals involved in causing hypertrophy?
- Mechanical signals (stretch)
- Vasoactive agents (alpha adrenergic)
- Growth factors (TGF-beta)
What is the limit to hypertrophy of the heart?
When enlargement of muscle can no longer compensate for increased burden
What is the mechanical signal for increased myocardial hypertrophy?
Increased stretch
What are the vasoactive agents signaling heart hypertrophy?
Alpha adrenergic agonists, like angiotensin
What are the growth factors that signal myocyte hypertrophy?
TGF-beta
How is myocyte hypertrophy effected? (3)
- Synthesis of contractile proteins
- Production of growth factors
- Induction of embryonic genes to increase performance
True or false: hypertrophied cells have increased DNA content
True– need more proteins per cell
What is the requirement of the cells of tissues that can undergo hyperplasia?
Must be capable of replication
What are the two physiologic forms of hyperplasia?
Hormonal hyperplasia (breast enlargement)
Compensatory hyperplasia (e.g. liver regrowth)
What is compensatory hyperplasia?
Increased tissue mass after damage or resection (think liver)
Pathologic hyperplasia usually results from what?
excessive hormones or growth factors acting on target cells
What is endometrial hyperplasia?
Hyperplasia d/t estrogen/progesterone imbalance
What is benign prostate hyperplasia (BPH) caused by?
Increased mitotic activity d/t increased androgens
True or false: pathologic hyperplastic processes remain controlled (except for CA)
True
What happens histologically in BPH?
Increased infolding d/t hyperplasia (nodular hyperplasia)
What are the histological changes in Grave’s disease to the thyroid?
Cells pile up on themselves
What is Grave’s disease?
Autoimmune disease where the abs act like signals to produce more TSH
Hyperplasia is the result of what?
Increased growth factor leading to increased output of new cells from stem cells
What the MOA of atrophy (2)?
Decrease in organelles/proteins
Increased protein degradation via ubiquitin
What are the signals of atrophy? (6)
Decreased workload Loss of innervation Decreased blood supply Inadequate nutrition Low endocrine Pressure
(BP, WINE)
How does pressure relate to atrophy?
Tissue compression leads to atrophy
What is senile atrophy?
Decreased blood supply to tissues, leading to atrophy
What is the initial atrophy response?
Decrease in cell size and organelles to reduce the metabolic needs of the cell to extent that they can survive
Atrophy immediately results in dead cells (true or false)?
False–just smaller
What is lipofuscin?
Bound residual cell debris from destruction of plasmalemma
What is autophagy? What process is it seen in?
Self=eating by starved cells to survive
Occurs in atrophy
What are the two cellular accumulations in atrophy?
Autophagic vacuoles and lipofuscin
How does aortic atherosclerosis result in kidney atrophy?
Decrease in blood supply to kidney
True or false: metaplasia is reversible
True
What is metaplasia?
reversible changes in which one differentiated cell types is replaced by another cell type that is better adapted to conditions
What is the effect of smoking on bronchi? What can this lead to?
Columnar cells turn to stratified squamous cells
May lead to CA
Barrett’s esophagus?
Changes of lower esophagus d/t changing from squamous epithelium to columnar with goblet cells
What is muscular dystrophy the result of?
Dystrophin gene messed up
What is CT metaplasia?
Formation of cartilage, bone, or adipose tissue in tissue that does not usually contain these elements
What is CT metaplasia the result of?
May be the result of tissue injury, rather than metaplasia
What type of CT metaplasia occurs in intramuscular hemorrhage?
Bone formation in muscle after intramuscular hemorrhage
What is the cellular mechanism underlying metaplasia? What are the three types of signals?
Result of reprogramming of stem cells that exist in normal tissues via cytokines, growth factors, ECM components
What is dysplasia?
Disordered growth
What disease process is dysplasia seen in? What cell type usually?
Precancerous in squamous epithelial cells (usually)
What are the histological changes is dysplasia? (2)
Disorderly arrangement of cells
Enlargement of nuclei, irregular borders, and hyperchromasia of individual cell nuclei
Intracellular accumulations are due to what?
Metabolic derangements
Pathological calcification are due to what?
Calcium deposition at site of cell death
In chronic cardiac overload, what genes are turned on?
genes expressed normally only in the neonatal heart are reactivated, and contractile proteins can switch to fetal isoforms, which contract more slowly
When does cell injury occur? Is cell injury reversible?
when limits of adaptive response to stimulus are exceeded. Can be reversible or irreversible
What are the three stages of progressive impairment that occur during cellular injury?
Adaptation, reversible injury, and cell death
What happens to myocytes when the limit of enlarged muscle mass is reached? (2)
Lysis and loss of myofibrillar contractile elements or myocyte death
Atrophy will continue until what point?
Until a new equilibrium is achieved so all cell can survive
How are proteins degraded in atrophy?
Poly ubiquitination and proteasomal destruction
