2. Relevance of Cell Injury to Disease Flashcards

1
Q

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

A

structure

function

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2
Q
• 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

A

growth
differentiation
accumulations
hyaline

physiologic
pathologic

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3
Q

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 ____)

A
reversible
organelles
protein
increase
autophagy
decrease
cell number
pathologic
physiologic
nutrients
demand
water
energy
non-functional
cachexia
cancer
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4
Q

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

A
aging
thymus
uterus
secondary sex characteristics
aging

hormonal

glandular elements

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5
Q

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

A

demand
innervation
oxygen
endocrine

different
pathologic
physiologic

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6
Q

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 ____))

A
reversible
cells
non-reversible
reversible
size
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7
Q

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)

A

increase
organelles
swelling

pathologic
physiologic
work
metabolic
persistent

PI3K
organelles
SER

molecular

subcellular organelles

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8
Q

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)

A

10X
smooth muscle
cell
function

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9
Q

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 (____)

A

workload
hypertension
normal size

volume
function
decrease

reversible
cell death

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10
Q

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

A

cell number
hormonal
compensatory

hormonal
growth factor

cancer
regresses

neurons
cardiocytes
striated muscles

marrow

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11
Q

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

A

lactating
glandular elements
normal size

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12
Q

Pathologic Hyperplasia

____

A

hyperthyroidism

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13
Q

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

A
3
hyperestogenism
testosterone
estrogen
stinosis
UTI
ascending
cancer
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14
Q
Gingival hyperplasia
• Drug related:
– \_\_\_\_
– \_\_\_\_ blockers 
– \_\_\_\_
– Oral \_\_\_\_
• characterized as redundant tissue of normal composition with elongated \_\_\_\_
A
anticonvulsants
calcium channel
cyclosporine
contraceptives
rete ridges
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15
Q

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

A

stem cells
undifferentiated mesenchymal cells
chronic irritation
reversible

pseudostratified columnar epithelium
stratified squamous epithelium
differentiation pattern

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16
Q

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 ____

A

columnar
stratified

focal

specialized
fragile
resistant

respiratory mucocilliary function
pulmonary infection

17
Q

The metaplasia process is not ____ > it’s still normal tissue in an inappropriate fashion (not a ____ change)

A

cancer

neoplastic

18
Q

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

A

squamous
columnar

GERD

red
whiteish

columnar
red/erythymatous

19
Q
  • 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

A

barrett
squamous
vitamin A

columnar
squamous

transitional
squamous

gladular
nonsecretory squamous

20
Q

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

A

myostis ossificans
synovial chondromatosis

epithelial

21
Q

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

A

cytoplasm
phagolysosomes
nucleus

metabolic derangement
abnormal

reversible

22
Q

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
A

steatosis
liver
niemann-pick disease

renal
protein folding

diabetes

exogenous
anthracosis
endogenous

23
Q

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 ____)

A

cholesterol
foam cells
smooth muscle
inflammation

fold
transported
renal tubules

lung
hemoglobin

24
Q

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 ____

A

fatty change

glycolipid intermediates
gangliosides

alpha 1-antitrypsin

25
Q

• 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

A

indigestible

pigments
coal dust

lysosomal enzyme

indigestible
elderly
ROS
peroxidation

26
Q

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

A
intracellular
extracellular
homogenous
H/E
descriptive
protein

immunoglobulin

27
Q

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

A

sublethal
DNA damage
replicative senescence
homeostasis

ROS
telomeres