2. Relevance of Cell Injury to Disease Flashcards
Disease is a manifestation of cellular injury:
– Lesions are the result of changes in the ____ of cells/tissues/organs resulting from injury
– Clinical signs and symptoms of disease are the result of changes in ____ of cells/tissues/organs resulting from injury
structure
function
• Adaptive Responses: • Adaptations of \_\_\_\_ and \_\_\_\_ (atrophy, hypertrophy, hyperplasia, metaplasia) • Intracellular \_\_\_\_ (lipids, proteins, glycogen, pigments) • \_\_\_\_ change
Can be ____ > represent response to normal stimulation by hormones, endogenous chemical mediators or to mechanical stress
Can be ____ > response to stress that allows cells to modulate structure/function to avoid injury
growth
differentiation
accumulations
hyaline
physiologic
pathologic
Atrophy
• A ____, adaptive response of the cell to reduce the mass
• Decrease in the number or volume density of ____
– Decrease in ____ synthesis
– ____ in protein degradation
– ____
• Leads to ____ in cell size and tissue/organ mass
• May lead to a reduction in ____
• May be ____ or ____
– resulting from decreased ____, decreased ____
Not simply cell shrinking and losing ____ > undergoing more significant changes (losing organelles, losing protein, activation of ubiq pathway)
May be due to autophagy > where the cell phagocytoses itself (for ____ purposes)
If stimulus is prolonged, cells may begin to drop off and die (can be replaced by ____ cells; adipose)
More severe form of atrophy = ____ > due to rapid breakdown of protein (seen in ____)
reversible organelles protein increase autophagy
decrease cell number pathologic physiologic nutrients demand
water energy non-functional cachexia cancer
Physiologic atrophy (often associated with development and ____)
• involution of the ____
• involution of the ____
– after parturition (1000g/5 cm wall to 100g/0.4 cm wall)
• involution/atrophy of ____
• ____ (senile atrophy; e.g., brain, heart)
All examples are ____
On the left is normal adult female breast; on the right is post-menopausal breast and there is a loss of ____ (they are maintained by hormones, as they changes, the glandular elements undergo atrophy and if the absence persists > drop out of the cells, and replaced by fat tissue
aging thymus uterus secondary sex characteristics aging
hormonal
glandular elements
Pathologic atrophy:
- Reduced functional ____
- Loss of ____
- Inadequate supply of ____; poor blood supply
- Inadequate nutrition
- Loss of ____ stimulation (e.g. testicular, breast, endometrium
Leg undergo atrophy due to lack of workload; top right: cross section of normal skeletal muscle; bottom right is a biospy of muscle fibers that are ____ (some are normal and some undergo atrophy) > he will now undergo PT and as you increase workload you will increase in size
Loss of endocrine stimulation can be both ____ and there are also ____ examples
demand
innervation
oxygen
endocrine
different
pathologic
physiologic
Left: normal muscle bundle where fibers are the same; middle: atrophic (____); right: atrophy continued and you see a drop out of ____ (perhaps from loss of innervation) (____ in sense of cell number, however, it is ____ in cell mass (the muscle fibers remaining will compensate and will increase in ____))
reversible cells non-reversible reversible size
Hypertrophy
____ in cell size and hence the size of the organ
• Increase in number and/or volume density of ____
– increased protein synthesis
– not simple ____
• ____ or ____ due to increased functional demand or by specific hormonal stimulation:
– Increased ____ demand
– ____ demand
– ____ tissue injury
- At the molecular level involves changes in biochemical pathways such as ____
- Most commonly refers to cells, but may be due to subcellular ____ such as effect of barbiturates on ____
PI-3K activated in hypertrophic tissue (____ event in addition to physiologic and pathologic)
Occurs in all aspects of cell, but in some instances, only occurs in ____ (effect of barb’s on SER)
increase
organelles
swelling
pathologic physiologic work metabolic persistent
PI3K
organelles
SER
molecular
subcellular organelles
Physiologic hypertrophy
Uterus goes from ____ its size to accommodate the fetus; involves an increase in number of ____ cells that make up uterus in addition to the size of each ____
Increase size > increase ____ (can contract more)
10X
smooth muscle
cell
function
Pathologic hypertrophy
Increase in mass/size due to an increase ____ (in this case, ____, compensate to increase in resistance) > remove the stress (this is an adaptation), it will return to ____
The heart as a result; as the cells get larger they are encroaching on the ____ the ventricle can handle in terms of blood > results in a loss of ____, resulting in a ____ in volume of blood supply being supplied to the body
____ up to a point, before you reach an irreversible stage (____)
workload
hypertension
normal size
volume
function
decrease
reversible
cell death
Hyperplasia
increase in ____
• Physiologic
– ____
– ____
• Pathologic
– excessive ____ stimulation
– excessive ____ stimulation
• Distinct from ____; cell proliferation remains controlled and hyperplasia ____ if stimulus is eliminated
Hyperplasia can occur in all tissue capable of proliferation (so everything besides ____, ____, and ____)
Donate a unit of blood, the ____ will start to increase in activity in order to replace lost cells
cell number
hormonal
compensatory
hormonal
growth factor
cancer
regresses
neurons
cardiocytes
striated muscles
marrow
Physiologic hyperplasia
Bottom left is ____ breast > expansion and proliferation of ____ (as a result of hormonal causes, physiologic control)
Remove hormones > tissue atrophy and return to ____ and function
lactating
glandular elements
normal size
Pathologic Hyperplasia
____
hyperthyroidism
Urinary tract > male has a prostate (____ lobes: 2 lateral lobes, and one medial lobe, lies beneath urethra)
Incidence of hyperplasia of prostate (due to ____, as a result of decrease of ____ levels); the lobes get larger as a result of ____ > begins to pinch the urethra (____); some urine stays behind and bacteria tries to ascend up the urethra; but voiding is hindered > development of ____ (____ infection)
Manifests to similar phenotype of ____, but it is NOT
3 hyperestogenism testosterone estrogen stinosis UTI ascending cancer
Gingival hyperplasia • Drug related: – \_\_\_\_ – \_\_\_\_ blockers – \_\_\_\_ – Oral \_\_\_\_ • characterized as redundant tissue of normal composition with elongated \_\_\_\_
anticonvulsants calcium channel cyclosporine contraceptives rete ridges
Metaplasia
Adaptive transformation of one type of fully differentiated (adult) type of tissue into another involving reprogramming of ____ and/or of ____ present in tissue; often in response to ____ (generally ____)
Most common form of metaplasia > smoker’s lung > lung is lined by ____ > important in secreting mucus; when epithelium is irritated by smoke the epihtelium begins to give way > transform into a ____ (one mature tissue type replacing another)
Change in the ____ of the cells results in the transformation; not a change within the cells themselves
stem cells
undifferentiated mesenchymal cells
chronic irritation
reversible
pseudostratified columnar epithelium
stratified squamous epithelium
differentiation pattern
Squamous cell metaplasia in lung (____ to ____ epithelium)
- Occurs as ____ or widely replaced epithelial lining in habitual smokers
- Smoking constituents cause chronic irritation
- Fragile pseudostratified epi lining of bronchi can’t tolerate noxious chemicals in smoke
- Replaced by rugged stratified epi
- Loss of function
You can see the goblet cells and ciliated border in the pseudostrat layer, and then nearby you can see the phenotype of the stratified epitheiulm (pseudostrat: it is highly ____, but it is also highly ____; stratified is more ____)
Loss of function with structural change > cilia are beating and goblet cells secrete mucus > ____ (foreign objects get trapped by mucus) > this function is lost upon transformation and the patients are normally coughing and they are more susceptible to ____
columnar
stratified
focal
specialized
fragile
resistant
respiratory mucocilliary function
pulmonary infection
The metaplasia process is not ____ > it’s still normal tissue in an inappropriate fashion (not a ____ change)
cancer
neoplastic
Barrett’s Esophagus (____ to ____ epi)
- Complication of ____
- Intestinal metaplasia (columnar epi containing Goblet cells) replaces esophageal squamous mucosa
- Likely due to chronic irritation from acid
Also occurs at the GEJ; in stomach > columnar epi, and tissue below junction is ____ (light reflects off of the BV); above junction: ____, because it is thicker and there is less reflection, so in this area it is stratified squamous epithelium (esophagus)
GERD > acid in stomach is regurgitated back up > constant exposure of squamous epithelim to acid results in a metaplastic change (not cancer); ____ epithelium begins to replace the strat squamous in the esophagus (the esophagus becomes more ____)
This is also ____ as long as the GERD is treated
squamous
columnar
GERD
red
whiteish
columnar
red/erythymatous
- Epithelial Metaplasia: – ____ esophagus
- Esophageal squamous epi is replaced by intestinal columnar due to gastric acid reflux
– Respiratory epithelium
• ____ metaplasia in respiratory epithelium due to smoke
irritation
• Deficiency in ____
– Cervix epithelium
• Lower endocervix changes from ____ to ____ epi due to
acidic vaginal environment
– Urinary bladder epithelium
• ____ epi replaced by ____ epi due to chronic irritation
– ____ epi to ____ epi- due to stones
barrett
squamous
vitamin A
columnar
squamous
transitional
squamous
gladular
nonsecretory squamous
Non-epithelial metaplasia – Bone formation in muscle
• ____-may be seen after bone fracture
– Cartilage formation
• ____- cells of synovial membrane become cartilage producing chondrocytes
This is an example of metaplasias not only occurring in ____ tissue
myostis ossificans
synovial chondromatosis
epithelial
Intracellular Accumulations
• Accumulations may be in ____, within organelles (often within ____) or in ____
• Accumulations may be synthesized by affected cells or produced elswhere
– Normal cellular constituent (e.g., water, lipids, proteins, carbohydrates) resulting from increased synthesis or decreased breakdown (i.e., ____
– ____ substance (mineral or products of infectious agents)
• If overload can be controlled/stopped, the accumulation is often ____ otherwise may progress to cell injury
cytoplasm
phagolysosomes
nucleus
metabolic derangement
abnormal
reversible
Intracellular Accumulations
• Lipids:
• Fatty change (____)-accumulation of triglycerides (seen in organs involved in fat metabolism: ____, heart)
• Cholesterol (atheroclerosis, cholesterolosis, ____, inflammation/necrosis)
• Proteins
• ____ disease, excess synthesis, defects
in ____, transport
• Glycogen (e.g. ____; storage disorder)
- Pigments:
- ____: carbon (____)
- ____: lipofuscin, hemosiderin, melanin
steatosis
liver
niemann-pick disease
renal
protein folding
diabetes
exogenous
anthracosis
endogenous
Intracellular Accumulations
____ required for the formation of PM; artheroclerosis > disease of arteries (fat accumulates within plaques, within ____ which are derived from macrophages or ____ cells); may accumulate in disorders with ____
Genetic defect may result in a sequence of a protein that cannot ____ properly and cannot get ____ to other organelles and accumulates; Renal disease > excess reabsorption of proteins and a large amount in ____
Pigments > colored substances that appear in segments in tissue (either grossly or histopathologically); carbon (anthracosis) > people accumulate resulting in changing in color of ____; hemosiderin > accumulates under injury (derived from ____)
cholesterol
foam cells
smooth muscle
inflammation
fold
transported
renal tubules
lung
hemoglobin
Intracellular accumulations of normal endogenous substance associated with abnormal metabolism (E.g., ____ in liver) or enzyme deficiency (e.g., Gaucher disease (____), Tay-Sachs disease (____)
Intracellular accumulation of abnormal endogenous substance associated with defects in folding, packaging, transport or secretion
– E.g., mutated forms of ____
fatty change
glycolipid intermediates
gangliosides
alpha 1-antitrypsin
• Accumulations due to ingestion of ____ material
• Accumulations of \_\_\_\_ – Exogenous: carbon from \_\_\_\_ (anthracosis) – Endogenous • Lipofuscin • Melanin • Hemosiderin
Accumulation due to indigestible material can be due to an enzyme deficiency (____ deficiency); lysosome is unable to break complexes down into smaller complexes (phagosome fuses with lysosome and material gets broken down in phagolysosome); or the failure can be in that it is missing a specific enzyme
Pigments fall in realm of ____; within cells lining alveoli is black material (left, this is carbon, probably an ____ person); middle: accumulation of lipofuscin > over years of injury via ____ (lipid ____); right: hemosiderin
indigestible
pigments
coal dust
lysosomal enzyme
indigestible
elderly
ROS
peroxidation
Hyaline change
- ____ and ____ alterations
- ____, glassy, pink areas in histologic sections stained with ____
- ____ term; rather than for cell injury. Associated with a number of alterations (not a specific pattern of accumulation) often associated with accumulations of ____
Right: plasma cell accumulation > super-plasma cells/cancer cells > producing so much ____ > takes on homogenous staining
intracellular extracellular homogenous H/E descriptive protein
immunoglobulin
Cellular aging
• Progressive decline in life span and functional capacity of cells due to cumulative ____ injury over life span
• Mechanisms that contribute to cellular aging:
– Accumulation of ____
– Decreased cellular replication (____)
– Defective protein ____
Cells have a finite lifespan; it may be encoded, part of it is due to DNA damage over time (due to ____, oxidative stress); related to ____, the cells losing the capacity to proliferate
sublethal
DNA damage
replicative senescence
homeostasis
ROS
telomeres
