Disease at the cellular level Flashcards
(202 cards)
1
Q
What is hypertrophy?
A
1) General increase in the bulk, not due to tumor formation
2) increase in size of cells not #
2
Q
What happens to tissue once it stretches or stress is put on a tissue?
A
It will adapt to the stress
3
Q
What is atrophy or hypotrophy?
A
wasting of tissue from death and reabsorption of cells, diminished cellular proliferation, decreased cellular volume, pressure, ischemia or malnutrition that leads to lessened function or hormonal changes
4
Q
What causes atrophy in the brain?
A
Aging and reduced blood supply
5
Q
How does a brain that has undergone atrophy appear grossly?
A
The brain has narrowed gyri and widened sulci
6
Q
What causes atrophy of the thyroid gland?
A
Longstanding autoimmune disease
7
Q
What is hyperplasia?
A
increase in # cells excluding tumor formation
8
Q
What causes endometrial hyperplasia?
A
Estrogen.
9
Q
What causes calluses on the heels of feet?
A
Stresses due to constant wear on feet (ie: tight shoes)
10
Q
What is BPH?
A
Benigh Prostatic hyperplasia
11
Q
What is hypoplasia?
A
incomplete development of tissue (ie: neural fold defects)
12
Q
What is metaplasia?
A
reversible replacement of one differentiated cell type with another differentiated cell type (ie: barrett’s esophagus where cells have migrated from the stomach to the esophagus due to constant stress)
13
Q
What is anaplasia?
A
A change in the structure of cells and a change in their orientation to each other.
14
Q
What is aplasia?
A
The defective development, or congenital absence of an organ or tissue
15
Q
What is dysplasia?
A
Abnormal tissue growth with loss of cell orientation, shape, and size
16
Q
Dysplasia is always what?
A
Pre-cancerous
17
Q
What is cell injury?
A
When the limits of adaptive response is exceeded
18
Q
What are the two types of cell injury?
A
Reversible and irreversible
19
Q
What is reversible cell injury?
A
When the abnormal stress/stimuli persists for a short period of time
20
Q
What is irreversible cell injury?
A
When the stress/stimuli persists or is severe
21
Q
Is time a factor in cell injury?
A
Yes, it is a major factor for example drinking 1 beer will cause some reversible change but drinking 1 beer everyday for 30 years will be a persistent stimulus leading to irreversible change
22
Q
What will swelling be like for reversible damage?
A
Generalized cell swelling
23
Q
What is a bleb?
A
A bubble or outpouching of plasma membrane
24
Q
Cells that bleb signify what type of cell injury?
A
Reversible
25
How does swelling of cells change for irreversible damage?
Increased swelling
26
What type of cell injury is plasma membrane damage?
Irreversible
27
What occurs in the ER with reversible Cell injury?
Swelling of the ER
28
What occurs in the ER with irreversible Cell injury?
Increased swelling of the ER
29
What happens to the ribosomes with reversible Cell injury?
Ribosomes detach from the ER
30
Cells with both reversible and irreversible damage have swollen mitochondria, but what is the difference in cells with irreversible damage?
They have vacuolization which is a Ca 2+ influx. due to membrane permeability
31
What happens to the nucleus in cells with reversible damage?
Reversible- chromatin clumps.
32
What happens to the nucleus in cells with irreversible damage?
Irreversible- Nuclear condensation, fragmentation and dissolution.
33
What is the term for nuclear condensation?
Pyknosis
34
What is the term for nuclear framentation?
Karyorrhexis
35
What is the term for nucleus dissolution?
karyolysis
36
What is the pH like for cells with reversible or irreversible damage?
Reversible has low intracelluar pH. Irreversible- continued low intracellular pH.
37
What type of cell injury is found with lysosome swelling and rupture?
Irreversible as necrosis will occur
38
What cell injury occurs when fat calcification begins?
Irreversible
39
What happens to reversible damaged cells when looking at them with light microscope?
They have fatty changes (steatosis).
40
Is nuclear clumping the same as nuclear condensation?
NO!
41
What is the difference between necrosis and apoptosis?
Necrosis- common after ischemia and chemical injury CELL SWELLING.
Apoptosis- is programmed cell death and CELL SHRINKAGE.
42
Does necrosis or apoptosis has neighbor or adjacent cell inflammation?
Usually necrosis
43
What happens to the plasma membrane during necrosis?
It is disrupted
44
What happens to the plasma membrane during apoptosis?
Intact/altered.
45
What happens with the cells contents with necrosis ?
enzymatically digested
46
What happens with the cells contents with apoptosis?
intact and packaged to be phagocytosed
47
What causes necrosis?
Inavriably pathologic
48
What causes apoptosis?
Often physiological
49
What does serum CK-MB check for?
Cardiac tissue ischemia
50
What does serum CK-BB check for?
Brain Tissue ischemia
51
What does serum CK-MM check for?
Generic muscle ischemia
52
What are the causes of cell injury?
1) O2 deprivation
2) Physical agents
3) Chemical agents/drugs
4) Infectious agents
5) Immunologic reactions
6) Genetic derangements
7) Nutritional imbalances
53
What are the two types of O2 deprivation cell injury?
Hypoxia and ischemia
54
What is hypoxia?
Inadequate oxygenation
55
What is ISchemia
Loss of blood supply
56
Can hypoxia occur without ischemia?
Yes, like in CO poisoning
57
Can ischemia occur without hypoxia?
No, hypoxia always occurs
58
What are some physical agents that cause cell injury?
trauma, burn, freeze
59
What are some chemial agents that cause cell injury?
cyanide, carbon monoxide, acetaminophen
60
What is an example of a genetic derangement that causes cell injury?
Sickle Cell Anemia
61
What is an example of a nutritional imbalances that causes cell injury?
Decreased calorie/protein, niacin, riboflavin
62
What are the types of biochemical mechanisms of cell injury
1) ATP depletion
2) Mitochondrial damage
3) High intracellular calcium
4) O2 deprivation & O2-derived free radicals
5) defects in membrane permeability
63
Mitochondrial damage that causes cell injury is due to what?
Increased Ca2+, oxidative stress, activated phospholiapase A2, Free fatty acids and ceramide
64
What is mitochondrial permeability transition?
Leakage of cytochrome c into the cytosol
65
Aerobic respiration gives us how much ATP?
36 atp
66
What do we get from anaerobic respiration?
2 ATP, and lactic acid.
67
Where does Kreb's Cycle Occur?
In the mitochondrial matrix
68
What does cytochrome c do once it is outside of the mitochondrial membrane?
It induces secondary apoptotic effects
69
What are the sources of internal calcium?
1) mitochondrial damage
2) cell injury (external calcium enters cell)
3) ER damage
70
Where will Vitamin E be doing free radical protection?
In the membranes.
71
Glutothione is stored mostly where and to do what?
Stored in the retina to protect against all redox reactions.
72
What is the role of P-450?
Detox. It is enzymes that increase the solubility of compounds and help excrete them.
73
What is the down side of P-450?
While detoxing it can make some reactive oxygen intermediates which can injure cells.
74
Where are the P-450 enzymes found?
In the Smooth ER of hepatocytes.
75
What process is NADPH oxidase found in?
Pentose Shunt
76
Is iron required in the human body?
yes but excess can cause oxidative changes
77
Is copper required in the human body?
Yes but only in trace amounts
78
Free radical injury is induced through what?
membrane lipid peroxidation, protein modification, DNA breakage.
79
How are free radicals degraded?
Through enzymes, spontaneous decay, and antioxidants.
80
Why is homogenated milk bad for us?
Xanthine oxidase is better absorbed in body and causes more free radicals in circulation
81
Reperfusion after anoxia (an abnormally low amount of oxygen in the body tissues) induces what?
Free radical production.
82
What are some free radicals found in the body?
Super oxide, peroxide, hydroxide and nitrous oxide
83
What are some antioxidants that neutralize the free radicals in the body that are found in the cytosol?
```
Superoxide dismutase
Glutathione
Peroxidase
Ferritin
Ceruloplasmin
Quercitin
```
84
What is the function of ferritin?
Moves iron around the body
85
What is the function of ceruloplasmin
Transports copper around the body
86
Where is quercitin found?
in orange peel (white part)
87
What can initiate injury via free radicals?
Radiation exposure, metabolism of drugs (phase I), redox reaction, nitric oxide, transition metals, leukocyte oxidative burst
88
How do free radicals cause cell injury?
Through membrane lipid peroxidation, protein modification and DNA breakage
89
What are 2 types of toxic cell injury?
1. Direct toxin.
| 2. Indirect toxin.
90
Give an example of a direct toxin?
Heavy metals like mercury.
91
How will heavy metals like mercury be toxic to cells?
It disrupts the S-S bonds.
92
Give an example of an Indirect toxin?
Carbon Tetrachloride (CCl4) it is metabolized in the liver to Carbon trichloride (CCl3) and this is more toxic.
93
The P-450 detoxes what?
Barbiturate.
94
What is an example of induction (hypertrophy) of smooth ER?
Barbituate detox by P-450
1) can lead to cell adaptation therefore decreased efficacy of medications such as phenobarbital for epilepsy when taken with alcohol
2) chronic barbituate use can lead to cell adaptation of hyper-detox and therefore a decreased effect
95
What will lysosomal catabolism do with a subcellular response to injury?
heterophagy and autophagy.
96
How is phagocytosis mechanically possible?
Clatharin pulls in substance and the plasma membrane wraps around it
97
What happens to the mitochondria with subcellular injury?
1) Increased number with cellular hypertrophy and decreased number with cellular atrophy.
2) Also mitochondria may assume extreme large and abnormal shapes with nutrient deficiency or EtOH use
3) abnormal cristae with mitchondrial myopathies (inherited)
98
What happens when the cytoskeleton undergoes subcellular injury?
Impaired:
1) intracellular organelle and molecular transport
2) basic cell architecture/shape/polarity
3) cell-to cell and cell-extracellular signals
4) Tissue integrity/mechanical strength (ie: desmosome anchorage)
5) Cellular mobility
6) phagocytosis
** thick scaffold/structural impairments
99
What are chaperones?
Heat shock proteins (HSP).
100
What will HSP (heat shock proteins) respond to?
Discovered with increased temperature but they respond to a variety of chemical/physical stimuli.
101
What are the 3 roles of HSP?
1. Protein folding.
2. Disaggregation of protein-protein complexes (unclumping).
3. Protein transport to cell organelles (chaperones).
102
What happens to albumin with increased temperature
It denatures
103
Where will proteins mostly break down at?
At sistein where the s-s bridges are.
104
What are the different types of necrosis?
1) Coagulative
2) Liquefactive
3) Caseous
4) Fat
5) Fibrinoid
6) Gangrenous
105
Coagulative necrosis happens with necrosis to what areas?
Heart, liver, and kidney.
106
Coagulative necrosis is a result of what?
Protein denaturation.
107
What will coagulative necrosis look like?
Preservation of basic cell outline for several days.
108
Liquefactive necrosis happens where?
Brain
109
Liquefactive necrosis is characteristic of what 2 things?
1. Bacterial infection.
| 2. CNS stroke.
110
Liquefactive necrosis is a result of what?
Enzymatic digestion.
111
Gangrenous necrosis is associated with what area?
Limbs and GI tract.
112
Gangrenous necrosis usually results in what?
limb with loss of blood and Coagulation necrosis.
113
What is wet gangrene?
Coagulation necrosis with liquifactive action of bacterial infection and attracted leukocytes.
114
Caseous necrosis occurs due to what?
It is seen in tuberculosis infections.
115
What is the appearance of caseous necrosis?
Cheesy white appearance.
116
Caseous necrosis is a distinct form of which type of necrosis?
Coagulative necrosis
117
What is makes caseous necrosis a special form of coagulative necrosis?
Tissue architecture is obliterated unlike coagulative necrosis
118
How does Caseous necrosis look microscopically?
1) amorphus granular debris of fragmented coagulated cell
| 2) amorphus granular debris enclosed within distinctive inflammatory border (granulmatous reaction)
119
Can scarring from caseous necrosis be seen via x-ray? And how long does scarring last?
Yes it can be seen in x-ray and the scarring remains with the patient for life
120
Fat necrosis occurs where?
In the pancreas
121
Is fat necrosis a typical necrosis pattern?
No
122
What will fat necrosis look like under microscope?
Foci of shadowy outlines of fat cells with basophilic calcium deposits surrounded by inflammatory reaction.
123
What will fat necrosis look like grossly?
Chalky area due to fat saponification
124
Is fat necrosis focal or widespread?
Focal area of fat destruction usually due to lipase release
125
What does P-450 do? What is an unfortunate result?
P-450 neutralizes toxins but creates free radicals
126
What is the stimulus for coagulative necrosis?
Hypoxia, toxins
127
What is the stimulus for apoptosis?
Physiologic and pathologic
128
What is the histology of the coagulative necrosis?
Cellular swelling
coagulative necrosis
organelle disruption
129
What is the histology for apoptosis?
Cellular shrinkage
Chromatin condensation
Apoptotic bodies
130
What is the DNA Breakdown in coagulative necrosis?
Random, diffuse
131
What is the DNA Breakdown in apoptosis?
Internucleosomal
132
What are the mechanisms of coagulative necrosis?
ATP depletion
Membrane injury
Free radical damage
133
What are the mechanisms of apoptosis?
Gene activation
Endonucleases
Proteases
134
What is the tissue reaction of coagulative necrosis?
Inflammation
135
What is the tissue reaction of apoptosis?
No inflammation
| Phagocytosis of ABs
136
During what instances does apoptosis occur?
1) Embryogenesis
2) hormone induction (menstruation)
3) immune cell-mediated death
4) injurious stimuli (ie: radiation, hypoxia)
5) regulation of cell population and tumor suppression
6) atrophy (ie: endometrial lining during menopause)
137
Which type of cell death is more controlled?
Apoptosis
138
Which type of cell death involves more cells?
Necrosis
139
What is the intrinsic (mitochondrial) pathway?
The permeabilisation of the mitochondria and release of cytochrome c into the cytoplasm. The cytocrome C then leads to caspase activation. Which then activates the executioner caspases and leads to apoptosis
140
What is the process of extrinsic (Death Receptor-initiated) Pathway?
It uses Fas Ligand to bring death domains (3 of them) in proximity and the Fas associated death domain which will lead to autocatalytic caspace activation -> executioner caspases -> apoptosis
141
Where is the brain of the cell?
Plasma membrane as it is the part that receives the information but (NB, it is the nucleus due to transcription and translation)
142
What are the 4 general mechanisms of intracellular accumulations?
1) abnormal metabolism (fatty change in the liver)
2) Mutations causing alterations in protein folding and transport, so that defective molecules accumulate intracellularly
3) A deficiency of critical enzymes responsible for breaking down certain compounds which cause substrates to accumulate in lysosomes (lysosomal storage diseases)
4) An inability to degrade phagocytosed particles, as in carbon pigment accumulation
143
What is an exogenous material for accumulation?
Coal particles (anthracosis)
144
What are the endogenous metabolites of accumulation?
Hemosiderin
| Lipids
145
What are are some sources of intracellular accumulations?
1) lipids
- steatosis
- cholesterol and cholesterol esters
2) protein
3) hyaline change
4) glycogen
5) pigments
146
Are the sources of intracellular accumulations exogenous or endogenous?
Endogenous although pigments can be both
147
Are fats well absorbed?
Yes, they cycle, being absorbed in the intestines but expelled by the liver
148
Does the heart use fats?
Yes, the heart uses fats and beta oxidation
149
What is steatosis?
Fatty change leading to abnormal triglyceride accumulation in parenchymal cells
150
What causes steatosis?
Alcohol abuse, toxins, protein malnutrition, diabetes mellitus, obesity and anorexia
151
What enzyme is responsible for alcohol-induced fatty liver?
Alcohol dehydrogenase
152
What does alcohol dehydrogenase do?
1) Interconversion between alcohols and aldehydes or ketones
2) Oxidizes methanol to produce formaldehyde
3) Oxidizes ethylene glycol to ultimately yield glycolic and oxalic acids
153
What derivative of lipids can cause intracellular accumulations?
Cholesterol and cholesterol esters
154
What is the microscopic appearance of lipid intracellular accumulations?
Foamy appearance
155
What are some examples of lipid intracellular accumulations?
1) atherosclerosis
2) Xanthhomas
3) Inflammation
4) Cholesterolosis
5) Niemann-pick disease, type C
156
Where does atherosclerosis due to lipid intracellular accumulation occur?
Plaque within the intima of large arteries
157
Where does Xanthomas due to lipid intracellular accumulation occur?
Hyperlipidemia found in skin and tendon masses
158
What occurs with inflammation due to lipid intracellular accumulation?
Phagocytosis of injured cell plasma membrane
159
Where does cholesterolosis due to lipid intracellular accumulation occur?
Lamina propia of Gall Bladder
160
What occurs with Niemann-Pick disease, type C due to lipid intracellular accumulation?
Lysosome storage disease
161
Which of the lipid intracellular accumulations are found within macrophage
Xanthomas
Inflammation
Cholesterolosis
162
What are some sources of protein intracellular accumulations?
1) Reabsorption droplets in the proximal renal tubules
2) Russell Bodies
3) Amyloidosis
4) Neuronal disease such as Alzheimer's, Huntington's, Parkinson's and maybe Diabetes Mellitus Type 2
163
What is the cause of reabsorption protein droplets in the proximal renal tubules?
kidney disease with protein loss
164
What are Russell bodies?
Distended Endoplasmic Reticulumwith large eosinophilic inclusions (excess secretory protein synthesis)
165
WHat is amyloidosis?
aggregation of abnormal proteins
166
What is the cause of the neuro disease due to protein intracellular accumulations?
Glutathione stimulating hormone (GSH)
167
What is hyaline change in terms of intracellular accumulations?
It is a pathologic descriptor meaning transparent appearance
168
What causes hyaline intracellular accumulation change?
Variety of alteration, not a specific pattern of accumulation
169
How does hyaline change appear in the microscope?
Gives a homogenous, glassy, pink appearance on H&E staining
170
What are some intracellular examples of hyaline change leading to intracellular accumulations?
1) Reabsorption droplets
2) Russel Bodies
3) Mallory alcoholic hyalin
171
What are some extracellular examples of hyaline change leading to intracellular accumulations?
1) Collagenous/fibrous tissue (scars)
| 2) Arterial wall hyalinization (Hypertension or DM2)
172
What are glycogen intracellular accumulations?
Clear Vacuoles within cytoplasm
173
What are the causes of glycogen intracellular accumulations?
1) glucose metabolism disorders (diabetes mellitus)
| 2) Genetic disorder (glycogen storage disease)
174
What are the two types of pigment intracellular accumulations?
1) Exogenous
| 2) Endogenous
175
What are the sources of exogenous pigments of intracellular accumulations?
Carbon (coal)
| Tatooing
176
What are the sources of endogenous pigments of intracellular accumulations?
1) Lipofusin
2) Melanin
3) Hemosiderin
177
What is lipofusin?
Lipids being oxidized or lipid peroxidation
178
What is hemosiderin derived from?
Hemoglobin (stored and eaten)
179
What is hemosiderosis?
Iron and RBC that are left (like the dark spots in a lung)
180
What is hemachromatosis?
More severe version of hemosiderosis
181
What are the two types of pathologic calcification?
Dystrophic calcification
| Metastatic calcification
182
Where does Dystrophic calcification occur?
Deposition occurring locally in dying tissue
183
What happens to the serum calcium level of the dystrophic calcification?
Nothing, it is normal serum calcium level
184
Is there any calcium metabolism pathology associated with dystrophic calcification?
No, no calcium metabolism pathology
185
What are some examples of dystrophic calcification?
Atherosclerosis of arteries, damaged heart valves
186
Where does metastatic calcification occur?
Deposition in otherwise normal tissue
187
What happens to the serum calcium level of the metabolic calcification?
Systemic elevation calcium levels in the blood and all tissues
188
What usually causes metastatic calcification?
Usually due to secondary hypercalcemia
189
What is the most common cause of hypercalcemia?
Hyperparathyroidism
190
What does calcitonin do?
Calcitonin is absorbed in the bone and decreases serum calcium
191
What does parathyroid hormone do?
Decreases calcium in bone and increases serum calcium
192
What are the causes of metastatic calcification?
1) increased parathyroid hormone
2) Bone destruction
3) vitamin D related
4) Renal failure
193
What causes parathyroid hormone to increase?
Primary tumor
194
What causes bone destruction?
Multiple myeloma and Paget's disease
195
What are some vitamin D related issues?
1) D toxicity
2) sarcoidosis
3) Williams Syndrome
196
What causes renal failure?
Potassium retention leading to secondary hyperparathyroidism
197
What ratio of calcium to phosphate does the body try to maintain?
2 Calcium to 1 Phosphate
198
What does metastatic calcification principally affect?
The intersttial tissues of the vasculature, kidneys, lungs, and gastric mucosa
199
How does multiple myeloma present in X-ray?
Widespread lucency in bone
- discrete "punched out" lesions
- uniform in size
200
What is a distinctive x-ray appearance for multiple myeloma?
Lucent, elliptical, subcortical shadows especially in long bones or endosteal scalloping
201
What happens to calcium levels in injured cells with dystrophic calcification?
The calcium levels will increase due to release from ER and mitochondria
202
What happens to mitochondrial initiation with dystrophic calcification?
The mitochondrial permeability transition increases and therefore calcium diffuses through into the cell.
