CELL INJURY 1 - normal cell and adaptive changes Flashcards
(35 cards)
list the important features of the cell and the main function of each
- nucleus: protein synthesis
- mitochondria: energy production
- lysosome: enzymatic activities
- cytoskeleton: mechanical support
- plasma membrane: fluid phospholipid bilayer
what leads to cell adaptation?
cellular stress
what are the 3 cell responses to stress/injury
- adaptive change
- reversible cell injury
- irreversible cell injury
- can also have defective/inadequate development
list the 5 types of adaptive change
- hypertrophy
- hyperplasia
- atrophy
- metaplasia
- dysplasia
list the 2 types of defective/inadequate development
- aplasia
- hypoplasia
3 major pathways of cellular adaptation
- increased cellular activity due to hypertrophy or hyperplasia
- decreased cellular activity due to atrophy
- modify cell type or position due to metaplasia or dysplasia
how do labile cells adapt to stress/injury?
- continuously replicating so high capacity to regenerate
- examples: bone marrow stem cells, epidermal cells, gut epithelium
how do stable cells respond to stress/injury?
- can regenerate when triggered by the right stimulus or lost
- if injury is severe enough or prolonged enough, dysfunction will occur
- examples: hepatocytes, osteoblasts, myocytes, renal tubular epithelium
how do permanent cells respond to stress/injury?
- cannot be replaced if lost bc they only divide during fetal life
- rather, cells repair themselves
- examples: neurons, cardiomyocytes
how do permanent cells repair themselves?
- dead cells removed
- collagen fills the gaps
- results in maintained tissue continuity and strength but loss of specialized function
= fibrosis or, in the brain, empty spaces
hypertrophy - definition, causes, 2 types, affected cells
- incereased organ size due to increased individual cell size
- induced by mechanical stress, growth factors, chemicals/drug exposure
- stable and permanent cells
- physiologic and pathologic
- often accompanies hyperplasia
physiologic hypertrophy
caused by:
- increased workload (mechanical or metabolic)
- hormonal stimulation (pregnancy)
pathologic hypertrophy
caused by:
- increased resistance to blood flow (e.g. myocardial hypertrophy 2ary to hypertension
- abnormal increase in hormonal stiumlation
- physical obstruction (e.g. bladder smooth muscle if prostate enlarged)
- genetically determined (e.g. hypertrophic cardiomyopathy in cats - esp. maine coons and ragdolls)
cellular changes and limiting factors in hypertrophy
cellular changes:
- increased membrane synthesis (larger RER = more proteins)
- increased ATP
- increased enzyme activity
- increased myofilaments
limiting factors:
- vascular and nutrient supplies available for oxidative phosphorylation
-
feline hypertrophic cardiomyopathy (HCM)
left ventricle (primary pump muscle) is thickened, leading to decreased volume in the chamber of the heart, and causing abnormal relaxation of the heart muscles
may cause the heart to beat rapidly, require more oxygen, and some cells may experience tissue starvation leading to ischemia causing endothelial cell injury and contribute to development of CHF and formation of blood clots in the left atrium
the blood clots may travel through the bloodstream and obstruct blood flow to other areas of the body (thromboembolism)
- thromboembolism causes hindlimb paresis/weakness in 10-20% of pts
- saddle thrombus 2ary to left atrial thrombosis
- most instances result in death or euthanasia
affected population:
- middle aged males predisposed
inherited component:
- maine coon
- ragdoll
- persion
- american shorthair
maine coon cats have a cardiac myosin binding protein C mutation with familial hypertrophic cardiomyopathy
- there is increased penetrance of hypertrophic cardiomyopathy in cats homozygous for the mutation
what is the major initiating trigger for cardiomyocyte hypertrophy?
mechanical stretch
cats with hyperthyroidism leading to/causing concentric myocardial hypertrophy
related to thyroid gland follicular hyperplasia or neoplasia causes increased levels of circulating thyroid hormones T3 & T4
- direct trophic action of thyroid hormones on myocardium - tells cardiomyocytes to work harder
- enhanced ability of myocardium to reply to adrenergic stimulus bc there are a greater # of adrenergic receptors with greater affinity for adrenaline
- peripheral vasodilation (with resulting increased heart rate)
- functional hypertrophy in response to increased peripheral tissue oxygen demands (metabolism/function) and heat dissipation
leads to concentric myocardial hypertrophy
- physiologic hypertrophic cardiomyopathy plus many lesions in the thyroid
how does chemical/drug administration cause hepatocyte hypertrophy?
- hepatocytes exposed to chemical or drug
- exposure causes enzyme induction - increased synthesis of enzymes involved in chemical/drug metabolism caused by toxins
- results in hepatocyte hypertrophy
e.g. rat treated with a COX inhibitor for 2 weeks had a dramatic increase of smooth endoplasmic reticulum (SER) bc the SER is the site of enzymatic activities (Cytochrome p450 & more) involved in chemical/drug metabolism
hyperplasia - definition, cause, and affected cell types
- increased organ size due to increase in cell number
- response to hormonal or growth factor stimulation
- can be a regenerative response to chronic tissue damage and cellular loss
tissues with dividing cells:
- labile and stable cells
hormone-induced hypertrophy/hyperplasia in the female reproductive system
- on the ovary, persistent corpora lutea
- causes increased progesterone
OR - excessive and/or persistent estrogenic stimulation
results in cystic endometrial hyperplasia
liver regeneration/compensatory hyperplasia
- inflammatory cytokine acts on hepatocytes
- hepatocytes enter G1 due to inflammation and respond to growth factors (TGF-a, EGF, HGF, etc.)
- growth factors induce hepatocyte proliferation
- after regeneration, growth inhibition phase begins (inc. cell cycle inhibitors, dec. growth factors, dec. metabolic requirements)
porcine proliferative enteropathy Lawsonia intracellularis
affects:
- pigs
- donkeys
- horses
- deer
- rodents
- non human primates
factors produced by L. intracellularis cause
- inhibition of enterocyte differentiation resulting in osmotic/malabsorptive diarrhea
- enterocyte proliferation resulting in mucosal hyperplasia in the gut
atrophy - definition, cause, cellular level actions, types
a decrease in cell size and organ
caused by:
- decrease in nutrient supply and/or function
at the cellular level:
- decreased protein synthesis
- increased breakdown of proteins and organelles
types:
- physiological
- pathological
physiological atrophy
decrease in cell size or number
decrease in organ size related to functional status or age
involution:
- due to altered or decreased hormonal stimulation (e.g. post partum uterus or mammary gland post lactation)
- due to apoptosis of individual cells (e.g. aged thymus)
