L3 - Cellular Response To Stress Flashcards
Homeostasis
ability of cells and tissues to maintain a steady state and handle physiological demands
Cellular adaptations
reversible changes in the number, size, phenotype, metabolic activity, or functions of cells bcz of a stimulus
-adaptation stops when stimulus is stopped-
Difference between physiologic and pathological adaptations
(Adaptations take several forms)
Physiologic- response of cell to normal stimulation ex. Hormones
Pathological- response that leads cells to change structure and function to escape injury
Hypertrophy definition
Increase size of cell = increase size of organ
It’s an adaptive response in cells with limited division capacity ex. skeletal and cardiac
Hypertrophy cause
- increased functional demand
2. growth factor or hormonal stimulation.
Hyperplasia definition
Increase in the number of cells in a tissue or organ (bone marrow after blood loss)
Adaptive response in cells capable of replication
Hyperplasia ex.
- In female breast at puberty and pregnancy ( lactation w/ more hormones)
- Thyroid goiter
Hypertrophy ex.
Thickening of left ventricle
Atrophy definition
Reduction in cell size by loss of cell substance bcz of decreased protein synthesis and increased protein degradation in cells
Causes of atrophy (6)
- Decrease workload
- Paralysis (loss of innervation)
- Ischemia (low blood supply cuz of arterial disease or atherosclerosis)
- Inadequate nutrition (low protein diet =muscle wasting aka cachexia)
- Loss of endocrine stimulation (ex. after menopause)
- Aging (brain and heart)
Atrophy ex.
Kindnys atrophy bcz of low blood supply
Metaplasia definition
Adaptive substitution of one type of differentiated cell for another type of cell as a response to chronic irritation
Cell injury progression
- Reversible: mild and sub lethal
2. Irreversible/ cell death: severe and lethal
What does cellular injury response depend on
- Nature of injury ( durations and severity)
- Type and adaptability of injured cell
Internal causes of cell injury
- Hypoxia (oxygen deprivation bcz of ischemia, cardio-resp failure, and anemia)
- Genetic defects (deficiencies in proteins)
- Autoimmune disease
- Aging
External cause of cell injury
- Physical or mechanical trauma-> high temp, UV light, radiation
- Chemical and toxins-> Drugs, alcohol, environmental and occupational hazards
- Microbial agents ->Bacteria, viruses
- Nutritional->low protein and vitamins and high cholesterol
Mitochondrial damage= ?
- low ATP =cellular swelling
- high ROS =damage lipids, proteins, DNA
Entry of ca2+= ?
- High mitochondria permeability
- activate cellular enzymes
Membrane damage= ?
Plasma membrane -loss of cell components
Lysosomal membrane -enzymes digest cellular components
=necrosis (low O2 and high Ca2+)
Protein misfolding - DNA damage= ?
Activate pro- apoptotic proteins
High ROS stimuli
Radiation, reperfusion, toxin
Oxidative stress
transient or persistent increase of ROS level that disturb cellular function and signaling pathways
How does ROS damage cells? (3)
- Lipid peroxidation (damage double bonds in membrane lipids)
- DNA fragmentation by reacting w/ thymine
- Protein cross-linking =loss of protein activity
Increased calcium= ?
=membrane damage
1-Activate phospholipase -> low phospholipids
2-activate protease->disrupt membrane and cytoskeletal proteins
=nuclear damage
1-activate endonuclease
=low ATP
1-activate ATPase
Swelling
- First manifestation of cell injury
- Reversible alteration
- Appears at organ level= pallor (appears pale bc of capillary compression)
- Increase organ weight
Structural changes of reversible cell injury
- Plasma membrane altered (blebbing and lose microvilli)
- Mitochondria swells
- ER dilates and ribosomes detach from it
- Nuclear alterations with clumping of chromatin
- The cytoplasm has phospholipid masses aka (myelin figures)
Hydropic change
accumulation of water in the cell
Fatty change
Lipid vacuoles appear in cytoplasm
Present in fat metabolizing cells (hepatocytes, myocardial cells)
Reversible
Cause of fatty change
defective transport of lipids (defects in synthesis of transport proteins)
Irreversible cell injury
Persistent or excessive injury beyond cell ability to adapt or maintain survival
Phenomena of irreversibility
Can’t correct mitochondria dysfunction
Disturbance in membrane functions
Lysosomal membrane injured
Necrosis
Cell death bcz of irreversible injury
Cells die in groups
Morphology of cell death (necrosis)
Pyknosis ->karyorrhexis ->karyolysis
Pyknosis
Nuclear shrinkage and increased basophilia
DNA condenses into a solid shrunken mass
Karyorrhexis
Nucleus fragmentation
Karyolysis
After 1-2 days nucleus disappears
DNase causes nuclear dissolution
Differentiate between early and necrotic injury
Early- shows surface blobs, increased eosinophilia in cytoplasm, swelling of cells
Necrotic- loss of nuclei, cell fragmentation, content leakage
Coagulation necrosis (ischemic necrosis)
Tissue architecture is preserved
Tissue stays firm bcz structural proteins and proteolytic enzymes are denatured -> blocking proteolysis
Leukocytes come to necrotic site and digest dead cells
Debris taken up by phagocytosis
Characterized by (infractions) in all solid organs except brain
Liquifactive necrosis
-Characterized in bacterial and fungal infections
-Microbial inflammation ->leukocyte enzymes digest and liquify the tissue
-Hypoxic death of cells in CNS
-Dead cells digested and removed by phagocytes
Ex. Cerebral infarction
Caseous necrosis
- Caseous = Cheese-like
- In tuberculous infection
- Architecture erased can’t see cellular outlines and the area surrounded by inflammatory border aka (granuloma)
Fat necrosis
- acute pancreatitis
- pancreatic enzymes leak and destruct fat cells (lipases)
- fatty acids released + calcium =fat saponification (chalky white areas)
Apoptosis
- programmed cell death
- single cell death
- eliminate unwanted cells to achieve homeostasis
- hormone dependent (ovary breast endometrium)
Pathological apoptosis
- DNA damage bcz of radiation and toxins
- Stress conditions (starving)
- High # Of misfolded proteins
- To remove cells injured by viruses
- Autoimmune disease cell death
Pathways of apoptosis
Mitochondrial pathway and death receptor pathway
Apoptosis -mitochondrial pathway
balance between pro- and anti-apoptotic proteins of the Bcl-2 family and cytochrome C =caspases activated from mitochondrial proteins that leak out = fragmentation of nucleus and cell
Apoptosis -Death receptor pathway
- eliminate self reactive lymphocytes
- damage by cytotoxic t lymphocytes
- activate caspases
What happens after capsases is activated?
->dna fragmented->cytoskeleton breakdown->apoptotic bodies form->bodies removed by phagocytosis w/out inflammation
What happens during an unfolded protein response?
The response activates signaling pathways that increase production of chaperones and reduce protein translation, thus reducing the level of misfolded proteins
Difference between necrosis and apoptosis
Necrosis- cell swells, plasma disrupted, enzymatic digestion of cell content and leakage, inflammation
Apoptosis- cell shrinks, plasma intact, intact cell content or apoptotic body release, no inflammation
Ferroptosis
cell death triggered by excessive intracellular
levels of iron
Necroptosis
cell death that shares aspects of both necrosis and apoptosis
Autophagy
Self destructive and survival mechanism Nutrient deprivation (stress) ->activate autophagy genes ->digest organelles + products used as cell nutrients
