1-Cellular Adaptations and Accumulations Flashcards
adaptation
state b/t normal/unstressed cell and injured/over stressed cell, reversible changes
new but altered steady state to survive
cellular responses to stress
- adaptive responses
- cell injury
- metabolic/subcellular alterations- intracellular accumulations, pathologic calcification
- cell aging
categories of adaptation
- physiologic- normal stimulation like hormones/endogenous chemical mediators
- pathologic- some same underlying mechanisms to modulate environment and escape irreversible injury
types of adaption
- hypertrophy
- hyperplasia
- atrophy
- metaplasia
hypertrophy
-inc in size of indiv cells and inc size of an organ
-no new cells just bigger bc inc syn of structural proteins and organelles
-coexist with hyperplasia (# of cells)
physio or pathologic
physiologic examples hypertrophy
- weight lifters- inc skeletal muscle with hypertrophy of indiv cells,
- pregnant uterus
pathologic examples hypertrophy
cardiac enlargement- hypertension, aortic valve disease (stenosis), MI
-myocytes nuclei enlarge (boxcar)
esp left ventricle
hypertrophy signals
signals:
1. mechanical (stretching)
2. vasoactive agents (alpha adrenergic agonist)
3. growth factors(TGF-beta)
limit reached when enlargement not be compensated
degenerative changes
hypertrophy mechanism
- trigger mech/agonist/GF
- inc signal transduction for protein syn and transcription
- induction of embryonic/fetal genes (mechanical) OR syn of contractile proteins (agoinsts) OR inc growth factors (GFs)
why happens?
hypertrophy
- in response to inc demand since most adult cells cannot divide
- balance to inc proteins and myofilaments, nuc with higher DNA content
hyperplasia
inc in # of cells in response to stimulus or persisten injury
-usually inc size(hypertrophy) and weight of organ
patho or physiologic
physiologic hyperplasia
- hormonal: puberty, pregnancy, proliferative endometrium
- compensatory: inc tissue mass after damage or resection (i.e liver fast regeneration)
pathologic hyperplasia
usually due to xs hormones or GF on target cells, will dissapear with stimulus so controlled process
- endometrial hyperplasia from estrogen/progesterone imbalace
- BPH, benign prostatic, from over exuberant mitotic activity from androgens
could also be from stem cells
atrophy
reduced size of organ from dec in cell size and organelles
-dec workload
-loss innervation
-dec blood supply
-inadequate nutrition
-loss endocrine stimulation
-pressure
atrophy process
- initial dec cell size reduces metabolic needs of cell to survive
- new equilibrium
- diminished function but not dead
- progress to irreversible cell injury/ death
atrophy mechanism
dec protein syn + inc protein degradation via ubiquitin proteasome pathway
autophagy of starved cells to find nutrients and survive
inc # of autophagic vacuoles bound and residual bodies (lipfuscin) if resist digestion
reversible
metaplasia
reversible change in one differentiated cell type to another cell type
-replaced by cells better able to withstand stress of a particular stressor
-from epithelial stem cells or undifferentiated mesenchymal cells thru genetic reprogramming
metaplasia examples
bronchi in smokers ciliated columnar cells replaced with stratified squamous
cancer if protective mechanisms lost
columnar to squamous most common, but could be oppo in esophagus
connective tissue- cartilage, bone, adipose tissue,
not usually physiologic, pathologic from injury
metaplasia mechanism
-reprogramming stem cells in normal tissues or undifferentiated mesenchymal in CT
-precursor cells diff along diff pathway
-signals like cytokines, GF, extracellular matrix components
dysplasia
disordered growth in squamous epithelial after common injury
progression of metaplasia into cancer
variations in size/shape, disorder arrangement, enlarge irregular nucleus, hyperchromasia,
intracellular accumulations categories
- normal endogenous substance: normal or inc rate, metabolism inadequate to remove, i.e fat
- abnormal endogenous: secondary to genetic or defects in metabolism/packaging/ transport/secretion
- abnormal exogenous: deposited and cannot be removed
mechanisms of intracellular accumulation
- abnormal metabolism
- alteration in protein folding and transport
- deficiency of critical enzymes
- inability to degrade phagocytosed particles
steatosis
fatty change
abnormal acc of triglycerides w/i parenchymal cells @ liver, heart, muscle, kidney
from toxins, protein malnutrition, diabetes mellitus, obesity, anoxia, alcohol
cholesterol and esters diseases
- atherosclerosis
- xanthomas- foamy cells under skin, acquired or hereditary, look like masses
- inflamm and necrosis
- cholesterolosis in gall bladder, foam cells
- niemann pick disease type C- lysosomal storage
foam cells can rupture so lipids into extracellular space = cholesterol cleft
atherosclerosis
@ plaques, smooth muscle, macrophages within intimal layer or aorta/large arteries
lipid vacuoles/foam cells yellow cholesterol laden atheromas
protein accumulations
less common than lipid acc
appear pink “hyaline” droplets in cytoplasm
from reabsorption droplets in proteinuria @proximal renal tubules, syn xs amounts, defects in folding
-Russell bodies immunoglobulins by plasma cells
-Mallory body from alcoholic liver disease
cytoskeletal abnormalities
defects in cell function locomotion, organelle movement
xxxxxxx
defects in protein folding
ER stress from misfolding of alpha helix or beta sheet (lead to apoptosis via caspases)
ubiquitin tags for degradation, chaperones help facilitate degradation and folding
examples of protein defects
- alpha 1 antitrypsin deficiency, buildup of intermediate so acc and trap in hepatocytes, emphysema and cyrosis of lungs
- amyloid- acc extracellularly, stiff tissues, interfere with normal function,
hyaline changes
nonspecific morphologic change of proteins to glassy, pink homogenous
intra: protein droplets @ tubules, russell bodies, mallory bodies, viral inclusions
extracellular: collagenized scars, damage glomeruli, atherosclerosis, amyloid
descriptive term
glycogen
abnormal metabolism of glucose or glycogen = xs intracellular deposits, clear vacuoles
diabetes @renal tubule epi, hepatocytes, cardiac myocytes, islets langerhand
glycogen storage diseases- enzyme defect, massive acc, i.e pompe
pigments
endogenous or exogenous colored substances from normal constituents or special
most common exo is carbon
exogenous pigments
- carbon- inhaled and transport to regional lymph nodes, darken tissue, emphysema or fibroblastic rxn
- tattoos: localized pigmentation of skin into dermal macrophages
endogenous pigments
aka lipofuscin
-insoluble brown/yellow from wear and tear ‘aging’ around nucleus
marker of free radical injury
melanin
endogenous
essential pigment for UV protection
-formed in melanocytes by tyrosine oxidation in epidermis
-can acc in basal keratinocytes or dermal macrophages
hemosiderin
endogenous
granular or crystalline storage of iron, hemoglobin derived
ferritin forms hemosiderin granules/aggregates if local or systemic xs of iron
from inc absorption of dietary, impaired use, anemias, transfusions
normal in small amounts
hemosiderosis progression
limited to liver,BM, spleen, LN
then liver, pancreas, heart, endocrine organs
maybe liver fibrosis, heart failure, diabetes
bilirubin
endogenous
normal in bile from hemoglobin
jaundice if xs
pathologic calcification
abnormal deposition of Ca salts mixed with iron, Mg, mineral salts
dystrophic (local in injured/dying tissues not in serum tho, necrosis) or metastatic (inc serum levels)
hypercalcemia
from bone cancer, high PTH in parathyroid, vitamin D disorders (sarcoid, renal failure)
in metastatic calcification @blood vessels, kidneys, lungs, gastric mucosa
