Cellular Adaptions Flashcards
A new steady state which lies between normal unstressed cell, and the injured overstressed cell, in which the cell can function and preserve viability.
Cellular 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
) Physiological adaptation
allows the cells to modulate their environment and ideally escape injury
e.g. hormones produced by tumors leading to endometrial hyperplasia
Pathological adaptation
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
change in cell type
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.
Metaplasia
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
Hyperplasia
Increase in cell size 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
Hypertrophy
Decrease in cell size
, 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
Atrophy
Causes of atrophy
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
Mechanism of atrophy
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
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
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
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
Ubiquitin
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.
Gravid uterus type of adaptation?
the gravid uterus occurs as a consequence of estrogen stimulation of both smooth muscle hypertrophy and smooth muscle hyperplasia
Mechanism of Hypertrophy
an increased synthesis of structural proteins and organelles leading to an overall increase in the workload of the organ.
The mechanisms of cardiac hypertrophy
mechanical triggers, such as stretch
trophic triggers, such as activation of α-adrenergic receptors
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
Causes of Hyperplasia
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)
Both hypertrophy and hyperplasia are ………., if the stimulus is removed
Reversible
pathologic hyperplasia constitutes a fertile soil in which cancerous proliferation may eventually arise.
. patients with hyperplasia of the endometrium are at increased risk of developing endometrial cancer
e.g. papillomavirus infections predispose to cervical cancers
Vitamin A deficiency causes
Metaplasia
Atp functions
the maintenance of cellular osmolarity
transport processes
protein and lipid synthesis
basic metabolic pathways
: unstable chemical species with a single unpaired electron in the outer orbital
Free radicals
Free radicals
1) Reactive nitrite species
2) Oxygen free radicals or reactive oxygen species (ROS) include:
Superoxide anion radicals (O2-)
Hydrogen peroxide (H2O2)
Reactive hydroxyl radical (HO.)
Sources of Free radicals
Inflammation Radiation Oxygen toxicity Chemicals Reperfusion injury
Targets of free radicals
DNA fragmentation
Protein cross-linking and fragmentation
may either block the formation of free radicals or scavenge them
Endogenous or exogenous antioxidants (e.g., vitamins E, A, and C, and β-carotene)
), Hg binds to the sulfhydryl groups of cell membrane proteins, causing inhibition of ATPase-dependent transport and increased membrane permeability.
Mercuric chloride poisoning (HgCl2)
Carbon tetrachloride (CCl4)
Used in dry cleaning
Converted to the toxic free radical CCl3· in the liver
