Lecture 1/2 - Cell Injury, Death, and Cell Adaptations Flashcards
(94 cards)
1
Q
Fundamental concepts in cell injury
A
- Clinical signs and symptoms are several steps removed morphologic changes that are preceded by the biochemical changes associated with cell injury
- Cell injury is common to all pathologic processes
- Cell injury results from a disruption of one or more of the cellular components that maintain cell viability
- Cell injury may be reversible or result in cell adaptation ofdeath
2
Q
Oxygen deprivation
A
hypoxia
ischemia
anemia
3
Q
infectious agents
A
bacteria
viruses
fungi
parasites
4
Q
physical changes
A
trauma electricity pollutants burns UV light radiation
5
Q
chemical agents and drugs
A
tobacco
alcohol
posions
Rx/ OTC drugs
6
Q
immunologic reactions
A
allergies and autoimmune disease
7
Q
genetic derangement
A
chromosome abnormalities
gene mutations
8
Q
nutritional imblanace
A
malnutrition
vitamin deficiecy
obesity
9
Q
What are the causes of cell injury from the cell’s perspective?
A
cell injury results from a disruption of one of more of the cellular components that maintain cell viability
-Divergent factors can act at the same point on the cell to induce cell injury
10
Q
The structures and processes that maintain cell viability include:
A
plasma membrane
mitochondria
macromolecular synthesis
nucleus
11
Q
There are several basic biochemical themes in cell injury, what are they?
A
ATP depletion generation of ROS (oxidative stress) loss of calcium homeostasis altered plasma membrane permeability mitochondrial damage DNA and protein damage
12
Q
Cell injury by impaired energy production - decreased oxygen (hypoxia) or no oxygen (anoxia) is due to:
A
impaired absorption of oxygen
decreased blood flow (ischemia)
disease of blood or blood vessels
inadequate oxygenation of the blood
13
Q
decreased oxygen impairs oxidative phosphorylation in the…
A
mitochondria
14
Q
reduced ATP reduces the ability of the plasma membrane to maintain homeostasis. This leads to …
A
a net gain of solute and an isosmotic gain in cytoplasmic water
15
Q
an isosmotic gain in water leads to:
A
- cell swelling with formation of cell surface blebs
- swelling of mitochondria
- dilation of the endoplasmic reticulum that leads to: detachment of ribosomes from RER and dissociation of polysomes an decrease in protein synthesis - can lead to increased lipid deposition
16
Q
reduced oxidative phosphorylation leads to increased ________
A
glycolysis
17
Q
increase glycolysis produces
A
lactic acid and inorganic phosphates that decrease intracellular pH leading to chromatin clumping
18
Q
what is hypoglycemia
A
reduced substrate for ATP production can result in the same basic patterns
From wiki: is a medical emergency that involves an abnormally diminished content of glucose in the blood.[1] The term literally means “low blood sugar” It can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose to the brain, resulting in impairment of function (neuroglycopenia)
19
Q
ROS are free radicals that are generated by
A
normal endogenous oxidative reactions in the plasma membrane, mitochondria, cytoplasm and peroxisomes
20
Q
Generations of ROS is associated with:
A
Inflammation oxygen toxicity chemicals irradiation aging
21
Q
Types of ROS (3 of them)
A
- Superoxide (O2-) - inactived spontaneously or by superoxide dismutase (SOD) to form H2O2
- Hydrogren peroxide (H2O2) - detoxified by glutathione peroxidase and catalase
- Hydroxyl radicals (OH) - generated by hydrolysis or water by ionizing radiation or by transitional metals such as Fe++ or Cu++
22
Q
ROS damage cells by:
A
- lipid peroxidation
- protein (cytoplasmic and membrane bound) cross-linking
- react with thymiddine and guanine to induce single strand DNA breaks
23
Q
intracellular and extracellular antioxidant systems act to reduce the effects of ROS by blocking their initiation or by inactivating them. These include:
A
- Intracellular - SOD, catalase and glutathione peroxidase
- Extracellular - vitamins E, A, and C and serum proteins that bind free iron (transferrin, ferritin) and copper (ceruloplasmin)
24
Q
Cytoplasmic Ca++ is maintained by protein sequestration in the…
A
cytoplasm, mitochondria, and endoplasmic reticulum
25
increase cytoplasmic Ca++ is a final common pathway of what?
cell injury
26
high levels of Ca++ will activate various degradative enzymes including:
phospholipases
proteases
endonucleases
ATPase
27
What are other causes of cell membrane injury? (5 of them)
1. Complement - C5-C9 membrane attack complex
2. Cytotoxic T cells - perforin
3. Viral
4. Bacterial endotoxins and exotoxins
5. Chemicals
28
Biochemical alterations occur prior to
morphologic changes
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degree of cell injury is partly determined by...
- cell type and its physiological state
| - the intensity, duration, and/or number of exposures to an etiological agent
30
cell injury may result in..
- reversible cell injury
- cellular adaptations associated with changes in cell number, size or differentiation
- cellular adaptations associated with abnormal accumulations
- cell death (necrosis or apoptosis)
31
reversible cell injury is acute in nature in occurs when the cell cannot maintain what?
normal homeostasis due to cell injury of short duration and minimal intensity
32
common etilogies of reversible(sub-lethal) cell injury include:
toxins
infectious agents
hypoxia
thermal injury
33
what are the two types of morphology with reversible cell injury?
hydropic change and fatty change
- Plasma membrane injury leads to increase intracellular Na+ that leads to an isosmotic gain in water
- organelles and cells swell, and the organ may appear pale and swollen
34
What are the concepts of cell death?
1. There is NO SINGLE biochemical event that equates with cell death
2. There are two morphologic forms of cell death - necrosis and apoptosis
3. Cell death leads to the release of cellular constituents into the extracellular environment
35
Morphologic changes in necrosis include: (5 of them)
1. Cell swelling
2. Protein denaturation yielding a glassy homogenous pink staining cytoplasm
3. Organelle breakdown may result in vacuolated cytoplasm
4. Nuclei changes include: karyolysis, pyknosis, karyorrhexis, or total loss
5. Inflammation - acute or granulomatous
36
The type of necrosis is dependent upon what?
patterns of enzymatic degradation and by bacterial byproducts when present
37
What is the most common from of necrosis?
coagulative
(cytoplasmic proteins are coagulated)
- The nucleus is lost, but the eosinophilic outline of the cell is retained for a short time prior to being removed by the inflammatory response
38
Which type of necrosis is described: tissue is totally digested by the release of lysosomal enzymes during the acute inflammatory response?
liquefactive necrosis ("pus", purulence)
39
Which type of necrosis is often associated with focal bacterial or fungal infections (eg. abscesses and wet gangrene), it is also seen in the CNS
liquefactive necrosis
40
Which type of necrosis is associated with M. tuberculosis infection?
caseous necrosis
41
Which type of necrosis displays gross features of the tissue having a white and "cheesy" appearance?
YUMMMMMMM this makes me want a cheeseburger
caseous necrosis
42
Which type of necrosis is described: microscopically charactererized as amorphous pink granular material within a ring of granulomatous inflammation and loss of tissue architecture
caseous necrosis
43
which type of necrosis is common in trauma to the breast or in cases of pancreatitis?
fat necrosis
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which type of necrosis has a gross appearance of chalky white-yellow
fat necrosis
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which type of necrosis give a "soap bubble" histologic appearance because of its dead adipocytes
fat necrosis
46
What is another name for programmed cell death?
apoptosis
47
What are the general concepts of apoptosis?
- morphologically distinct, gene directed, form of individual cell death
- it has a physiologic role
- diseases may arise from an increase or from a decrease in the rate of apoptosis
48
Morphologic features of apoptosis include: (4 of them)
1. Cell shrinkage
2. Chromatin condensation followed by fragmentation
3. Apoptotic bodies formation
4. Phagocytosis of the apoptotic bodies without a significant inflammatory response
49
What are the SIGNALING mechanisms of apoptosis?
```
intrinsic program
"death signals" (e.g. Fas- ligand binding to Fas receptor)
removal of a trophic signal (hormones)
ROS, radiation and toxins
effect of cytotoxic T cells
```
50
What are the CONTROL AND INTEGRATION mechanisms of apoptosis?
(two pathways)
1. direct signaling (e.g. Fas ligand, TNF binding)
| 2. regulation of mitochondrial permeability
51
In the control and integration mechanisms of apoptosis what is the role of the Bcl-2 gene?
Bcl-2 gene family serve as on and off switches that regulate the membrane permeability of the mitochondria (Bcl-2, Bax, Bak)
* Bcl-2 and cl-x gene products INHIBIT apoptosis
* Bax and bax gene products STIMULATE apoptosis
52
What is released from the outer mitochondrial membrane and serves to disrupt the inhibitory function of Bcl-2, favoring apoptosis?
cytochrome-c
53
mechanisms of apoptosis category execution - what are caspases?
apoptosis signaling pathways converge on an autocatalytic proteolytic cascade of caspases.
Their substrates include: cytoskeletal and nuclear matrix proteins, DNAse and transcription proteins
54
In apoptosis the mitochondria release Ca that activates which two enzymes?
1. transglutaminases cross link cytoplasmic proteins
| 2. Endonucleases cleave DNA at the linker regions b/w nucleosomes
55
In apoptosis how are dead cells removed?
- phagocytosis by neighboring cells and macrophages
| - little or no inflammation
56
How is apoptosis difference than necrosis in relation to STIMULI?
apoptosis: physiologic or pathologic
necrosis: hypoxia or toxins
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How is apoptosis difference than necrosis in relation to: MORPHOLOGY?
apoptosis: single cells, cell shrinkage, condensed chromatin, intact plasma membrane, apoptotic bodies
necrosis: multiple cells, cellular swelling, lysed plasma membrane, organelle disruption
58
How is apoptosis difference than necrosis in relation to: MECHANISMS OF DNA DESTRUCTION?
Apoptosis: ATP DEpendent process, gene activation and endonuclease mediated DNA fragmentation
Necrosis: ATP INDEPENDENT process, random, diffuse, free radicals, membrane injury
59
How is apoptosis difference than necrosis in relation to: TISSUE REACTION?
apoptosis: minimal inflammation, phagocytosis of apoptotic bodies
necrosis: inflammation
60
Chronic cell injury leads to cell adaptations, the etiological factors are the same as those that cause reversible cell injury or cell death, but differ in....
duration and intensity
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cell adaptations include:
- alterations in cell size (atrophy vs. hypertrophy)
- alterations in cell number (hyperplasia)
- alterations in cell differentiation (metaplasia)
- intracellular accumulations
62
What is the definition of atrophy
a decrease in cell size and function
| *there is often concurrent decrease in organ size and/ or function
63
What is the etiology of atrophy?
- decreased workload
- loss of innervation
- decreased blood supply
- inadequate nutrition
- decreased trophic signals
- aging
- local pressure
64
what is the morphologic appearance of atrophy?
- atrophic cells are shrunken
| - there is a reduction in structural components
65
what is the definition of hypertrophy?
an increase in cell size
- associated with an increase in functional capacity
- tissue and/ or organ size may increase and may be accompanied by an increase in cell number (hyperplasia)
66
in reference to hypertrophy, what is a NORMAL (physiologic) response to trophic signals (hormone stimulation)?
smooth muscle hypertrophy in the pregnant uterus
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in reference to hypertrophy, what is an ABNORMAL (pathologic) response to trophic signals (hormone stimulation)?
- exogenous anabolic steroids induced muscle hypertrophy
| - overproduction of TSH due to iodine deficiency induces thyroid follicle hypertrophy (goiter)
68
increased functional demand (muscle hypertrophy) skeletal muscle cells hypertrophy in response to...
exercise
69
When and why do myocardial cells hypertrophy?
due to increased workload of pumping against impaired aortic outflow or systemic hypertension
70
What is the definition of hyperplasia?
an increase in the number of cells in a tissue or organ
- may involve the proliferation of epithelial and/ or stromal cells
- cell proliferation is stimulated by trophic factors (hormones and cytokines)
- may increase the risk for subsequent neoplastic transformation
71
what is the etiology of hyperplasia? (in relation to hormones)
hormones can stimulate hyperplasia:
- endometrial glandular cells during the normal menstrual cycle
- gynecomastia (hyperplasia of the breast in men) can be iatrogenic in its etiology (i.e. secondary to estrogen treatment for prostate cancer
- erythrocyte hyperplasia can follow ectopic production or erythropoietin
72
What is the etiology of hyperplasia? (in relation to growth factors)
growth factors can stimulate hyperplasia:
- wound healing represents hyperplasia of CT cells as well as associated epithelial cells
- lymph node hyperplasia is due to lymphocyte hyperplasia resulting during chromic inflammation and an immune response
- epidermal cell hyperplasia leads to a callus due to repeated friction
- chronic inflammation can induce hyperplasia of overlying epithelial cells
73
definition of metaplasia
one adult cell type is replaced by another adult cell type in response to chronic stress
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intestinal metaplasia relates to replacement of
normal epithelium with goblet cells and other intestinal mucosal type cells
75
what is Barrett's esophagitis?
the normal stratified squamous epithelium of the esophagus being replaced due to prolonged exposure to reflux gastric contents
76
squamous metaplasia is conversion of
normal columnar eptiehlium to stratified squamous epithelium
77
what are some examples of squamous metaplasia
- Resp. tract in response to chronic smoking
- ductal epithelium of various glands in response to vitamin A deficiency
- cervix in response to various agents
78
categories of cell accumulations include:
-excess of normal cellular constituent such as water, lipids, proteins, and carbohydrates and pigments that may be exogenous or endogenous
79
the mechanisms of intracellular accumulations include:
- abnormal metabolism
- lack of enzyme
- abnormal protein folding or transport
- ingestion of indigestible material
80
what is a steatosis
it is a fatty liver
| - an abnormal accumulation of triglycerides within paenchymal cells of the liver, heart, kidney, and skeletal muscle
81
what is the etiology of lipid accumulation (steatosis)
```
obesity
diabetes
alcohol
anorexia
toxins
protein malnutrition
```
82
what is the gross appearance of a fatty liver?
enlarged yellow (3-6 kg) liver
83
what is the microscopic appearance of a fatty liver?
hepatocytes contain clear cytoplasmic vacuoles that displace the nucleus
84
where does cholesterol primarily accumulate?
macrophages (foam cells)
- skin - in subepithelial macrophages forming a xanthoma
vessels - in atheromas of atherosclerosis
85
what is the histology of proteins
eosinophillic cytoplasmic droplets, vacuoles, or aggregates
86
what are examples of proteins?
- alpha 1 anti trypsin deficiency - impaired folding due to gene mutation
- mallory bodies - impaired secretions due to improper folding or precipitation
- neurofibrillary tangles in Alzheimer's disease - accumulations of microtubule associated proteins and neurofilaments
87
what is the morpholog of glycogen/ glucose?
clear cytoplasmic/ nuclear vacuoles, PAS (+)
88
what is a glycogen storage disease?
abnormal glycogen metabolism due to enzyme deficiency
89
what are some examples of exogenous pigments?
- carbon is accumulated in makcrophages, (anthracosis vs. pneumoconiosis)
- tattoos - pigment is accumulated locally
90
what is lipofuscin?
"wear and tear" brown-yellow granular pigment
| -lipoprotein complex due to ROS peroxidation of membranes
91
definition of melanin?
black-brown pigment produced by melanocytes but accumulated in adjacent epidermal cells and in macrophages
92
what is hemosiderin?
- a yellow brown pigment represents aggregates of ferritin micelles
- its accumulation arises from excess iron locally due to hemorrhage and can lead to hemosiderosis
-
93
what is hemochromatosis
genetic disease associated with cell death due to uncompensated hemosiderin accumulation
94
what is bilirubin?
- brown yellow pigment
- end produce of heme metabolism
- accumulates in heptaocytes and bile ducts due to hemolysis, obstructed bile flow and or hepatocellular disease
