Cell Injury Flashcards

1
Q

Founder of Modern Medicine

A

Virchow

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2
Q

Father of Modern Medicine

A

Osler

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3
Q

somatic death

A

death of the entire organism

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4
Q

agony

A

transition time from life to death characterized by loss of function and coordination of respiratory system, cardio vascular system, CNS leading to general organ dysfunction

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5
Q

unequivocal signs of death

A

rigor mortis, pallor mortis, algor mortis, livor mortis, decomposition, and skeletonization/mummification

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6
Q

equivicol signs of death

A

your “vital signs” - pulse/heart rate, respiratory rate, body temp, atony, loss of reflexes, mydriasis

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7
Q

pallor mortis

A

skin pallor which occurs within 20 minutes of death in humans

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8
Q

rigor mortis of the heart and diaphragm

A

1-2 hours after death

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9
Q

rigor mortis of the mandibular joint/chewing musculature

A

2-4 hours after death

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10
Q

livor mortis

A

dark spots appear in the skin in lower portion of body because of gravitational pooling to the down side of the body

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11
Q

algor mortis

A

body temp decreases to ambient temp

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12
Q

rate of decomposition is inversely correlated to…

A

the decrease in body temp - a body that cools down quickly preserves better

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13
Q

skeletonization/mummification

A

skeletonization - final stages of decomposition during which last vestiges of soft tissues of a carcass have decayed
mummification - drying of tissue, which occurs in some cases like the dessert

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14
Q

Postmortem autolysis/decomposition

A

begins by progressive release of enzymes and slowly by saprphytic bacteria escaping from the gut

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15
Q

Postmortem Clotting

A

homogenous, diffusely red, elastic, don’t adhere to endocardium, can be readily pulled out of vessels

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16
Q

chicken fat clots

A

when red blood cells separate from plasma and turn yellowish (esp. in animals with high fibrinogen - horses and in heart ventricles)

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17
Q

Hemoglobin Imbibition

A

HgB released by RBC breakdown staining tissues

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18
Q

Bile Imbibition

A

leakage of bile from gall bladder staining tissues green to yellow

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19
Q

Pseudomelanosis

A

artificial black discoloration due to saprophytic/putrefactive bacterial production of hydrogen sulfide and iron, formation of FeS or sulfmethemoglobin

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20
Q

Putrefaction

A

(rotting) enzymatic decomposition of organic material with the production of smelly compounds (hydrogen sulfide, iron sulfide, ammonia) by saprophytic/putrefactive bacteria

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21
Q

Postmortem Emphysema

A

(bloating) when saprophytic bacteria produce gas

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22
Q

euthanasia artifacts

A

splenic congestion - enlarged diffusely dark red spleen

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23
Q

Etiology

A

Cause

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24
Q

2 major etiologic factors

A

1) Intrinsic “endogenous” factors (genetic)

2) Acquired “exogenous” factors (infectious, nutritional, chemical, physical)

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25
Pathogenesis
How or the sequence of events in response of cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of disease
26
lesions
morphologic changes in tissues and chemical alterations
27
Which is more definitive? An etiologic diagnosis or a morphologic diagnosis?
Etiologic diagnosis - names the specific cause of the disease while a morphologic diagnosis is based on the lesions in the tissues and describes them.
28
Morphologic diagnosis
the long one - ex: Moderate, subacute, diffuse, fibrin-necrotic tracheitis
29
chimerism
genetically different cells in one individual that are derived from different zygotes - free martins where blood cells are exchanged between male and female twin cattle via communicating placentas
30
True/False: somatic cell mutations are inheritable?
False! Germ cell mutations are inheritable
31
Ehlers Danlos Syndrome
collagen defect
32
3 consequences of enzyme defects
1) storage diseases 2) reduction of functional protein due to metabolic block of enzyme function 3) Increased concentration of toxic products that can no longer be detoxified due to enzyme defect
33
Mutation of Multi Drug Resistance (MDR) gene 1
MDR-1 encodes fo P-glycoprotein which is a cell membrane transport protein which prevents cells from accumulating toxic substances such as ivermectin - autosomal recessive disorder
34
Mitochondria have how many genes?
37
35
What is the first organ to be affected when mitochondria do not function properly?
CNS
36
euploid karyotype
normal chromosome numbers
37
HSPs
protect secondary and tertiary structures during hyperthermia and aid in the removal of damaged denatured proteins
38
Malignant hyperthermia
point mutation in ryanodin receptor of muscle cells causing the increased release of Ca, thus muscle contractions, and hyperthermia Happens under stressful situations to pigs mostly
39
Insolation
local hyperthermia affecting the brain
40
Combustio/scolding
1-4 = C. erythematosa --> bullosa --> escharotica --> carbonisata
41
Congelatio
(frost bite) - C. erythematosa --> bullosa --> escharotica/gangraenosa --> complete freezing
42
Heat shock
difficult diagnosis - reddened meninges, brain and organ edema
43
Stages of burns
Erythematosa - skin/mucous membrane reddening and edema Bullosa - blisters, possible fever Escharotica - epidermal necrosis, poorly healing ulcers/keloid formation Carbonisata - scorched skin opened joints in abnormal positions
44
Stages of freezes
first degree - ischemia and then erythema (skin reddening after warming up) Second degree - formation of blisters and chilblains Third degree - gangraenous changes due to thrombosis and bacterial infections
45
UV light
sun burn - causes pyrimidine dimers in DNA to form, impairing repair mechanisms and ultimately mutation of protooncogenes and tumor supppressor genes causing squamous cell carcinomas and malignant melanomas
46
Ionizing radiation
X rays, gamma rays - mitotic cells vulnerable - formation of free radicals
47
Photodermatitis
Primary - intake of photodynamic compounds such as cancer drugs which absorb UV light and form free radicals Secondary - impairment of porphyrin metabolism and metabolites are photodynamic (hereditary of cattle causing pink tooth) Hepatogene photosensitivity - chlorophyll is metabolized to phylloerythrin by ruminant bacteria which is normally metabolized in healthy livers, persists in circulation in animals with liver disease
48
Does alpha, beta, or gamma radiation penetrate the entire body?
gamma radiation
49
True/False: tissues with a high dry weight are most vulnerable to radiation?
False: Tissues with a low dry weight or high water content are most vulnerable
50
True/False: The unit of radioactivity is the Becquerel?
True
51
Is the average natural radiation higher in Germany or the US?
USA :(
52
Which isotope has the longest half life time? Iodine, Caesium, Strontium, or Plutonium?
Plutonium 239 has a half life of 24,000 years!
53
Skin Reaction to radiation?
1st degree - Epilation - loss of keratin 2nd degree - Erythem - dermatitis, hair loss 3rd degree - Exudative - exudative dermatitis with blisters and alopecia 4th degree - necrosis and ulcers (radiation dermatitis)
54
Cachexia
protein-energy deficiency syndrome/marasmus (relative lack of energy supply): severe form of emaciation characterized by serous atrophy of adipose tissue
55
True/False: Total inanition refers to the consumption of an inadequate amount of food?
False: that defines relative inanition, total inanition is the complete lack of food intake
56
4 phases of starvation
Phase 1 - glycogen mobilization from liver and muscle, than fat from fat stores Phase 2 - increased gluconeo (with adrenocortical hyperplasia due to glucocorticoid synthesis) and degradation of muscle protein Phase 3 - hypoproteinemia --> edema Phase 4 - hormonal insufficiency with hypoglycemia (cause of death)
57
True/False: Hypertone dehydration is due to the loss of water but not sodium?
True! Hypotone dehydration is due to the loss of sodium due to insufficient renal resorption
58
Diabetes Mellitus is such that large quantities of ____________ are excreted into the urnine exceeding the reabsorption capacity of the tubules. Water then has to follow due to osmoality of urine leading to __________ and __________?
glucose, PU/PD
59
True/False: Hypertone hyperhydration is when the rate of hydration with physiologic solution is higher than renal excretion capacity?
False, this defines isotone hyperhydration. Hypertone hyperhydration is due to increased sodium up take and decreased sodium excretion
60
Differentiate between commensalism, mutualism, and symbiosis
commensalism is when guest lives from host with no benefit or disadvantage for the host mutualism is when it benefits both symbiosis is when it is a necessary relationship for both
61
Latent vs Tolerated vs Occult inflammation
latent - balance tolerated - infectious organism is recognized as self occult - infectious organism proliferates with cell division but the organism isn't infectious
62
True/False: Age technically is not a cause of death?
True, eventually cells will have a diminished capacity to carry out normal functions to to an accumulation of life's injuries
63
What is the most common cause of cell injury?
Hypoxia
64
Stages of progressive cell impairment
adaptation, reversible injury, and cell death
65
Hallmarks of reversible cell injury
ATP depletion, cell swelling due to changes in ion concentrations and water influx
66
Cytomorphologic changes of Irreversible cell injury
Plasma membrane damage, mito swelling, Ca entry into cell and in mito, lysosomal swelling
67
What are the 5 intracellular systems vulnerable to injury?
Cell membranes, mitochondria and aerobic respiration, protein synthesis in the RER, genetic apparatus, cytoskeleton
68
What is the most common expression of cellular degeneration?
Cell swelling or hydropic degeneration due to cells not being able to maintain ionic and fluid homeostasis
69
Difference between sensu lato and sensu stricto?
Sensu lato is cell swelling due to water intake or material accumulation (lipids, glycogen, etc) and sensu stricto is the swelling of a cell due to water intake only
70
Scenario - a dog has the liver enzyme alanin amino transferase (ALT) in its blood. What does this tell us?
The dog has liver damage
71
If you cut an organ upon necropsy and it bulges from this cut surface, what does this tell us?
the organ has cell injury causing cells to swell and thus the organ. The capsule will hold this swollen organ together, but will bulge when cut.
72
What does the suffix -osis mean?
It is used for an organ diagnosis dominated by degenerative cellular changes.
73
Hypoxia and Ischemia vs just hypoxia
During purley hypoxic conditions the glycolytic energy production can continue, during ischemia, even the delivery of substrates needed for glycolysis is compromised
74
Which cells have a high sensitivity to hypoxia? Intermediate sensitivity? (hepatocytes, neurons, cardiomyocytes, renal epithelial cells, enterocytes)
Neurons - high (3-5 minutes) | Hepatocytes, cardiomyocytes, renal epithelial cells, enterocytes = intermediate (20-120 minutes)
75
mitochondrial permeability transition
formation of non selective high conductance channels in inner mito membrane , initially reversible but quickly becomes permanent Leakage of Cytochrome C causes apoptosis
76
2 Features associated with cell death (even though there is no definitive stage beyond which the cell is doomed to destruction)
1) unable to reduce mitochondrial dysfunction even after resolution of the original injury 2) develop profound disturbances in membrane function
77
Oncosis vs Apoptosis
Oncosis - degenerative cellular changes - when damage to membranes is severe, lysosomal enzymes enter cytoplasm and digest the cell along with surrounding tissues due to loss of membrane Apoptosis - DNA damage can induce apoptosis and does not necessarily mean a loss of membrane integrity
78
True/False: Oncosis is always pathologic where as apoptosis can also serve normal functions?
True!!
79
Which cellular pathways are very sensitive to ischemia?
Oxidative phosphorylation (ATP) and glycolysis
80
What is reperfusion injury?
When blood flow and thus oxygen is restored to cells, accelerating cell injury due to sudden increase in Ca and oxygen
81
What does an increase in cellular Ca cause? When do we see this?
It activates ATPase, phospholipase, protease, and endonucleases. This is seen in reperfusion injury.
82
How are free radicals generated?
by product of oxidative metabolism, exposure to radiation, toxic gases, chemicals or drugs, or on purpose by inflammatory cells such as macrophages to fight microorganisms
83
Which molecules are especially at risk to free radicals?
proteins, membrane lipids (with high unsaturated fatty acids with double bonds by hydroxyl radical), and nucleic acids
84
What do antioxidants do?
They block the formation of free radical formation or inactivate free radicals. Examples are Vitamins E and A as well as water soluble ascorbic acid (Vitamin C)
85
Coagulation necrosis
most common manifestation of cell death due to hypoxic/ischemic death of cells in all tissues except brain Lighter/pale in color, firm, dry eosinophilia, glassy or hyalinized
86
pyknosis
shrunken and densely basophilic nuclei
87
karyorrhexis
nuclear fragmentation
88
karyolysis
dissolution of the nucleus (fading of chromatin to DNAases
89
infarction
necrosis due to ischemia
90
2 types of infarctions
White (arterial infarcts) - affect solid organs and intestinal segments with lacking arterial collateral blood supply Red (venous infarcts)- due to occlusion of veins so that blood enters but is not drained from affected tissues
91
Liquefactive necrosis
enzymatic digestion of cells rather than protein denaturation, seen in bacterial infections or in hypoxic damage to the brain results in liquefied tissue, pus or dead WBC, neutrophils
92
Caseous necrosis
due to specific bacterial diseases, grey-white, dry, friable, cheese like, do not retain cell outline like in coagulation necrosis, do not undergo complete dissolution of cells like in liquefactive necrosis
93
dry gangrene
coagulation necrosis of an extremity
94
wet gangrene
coagulative necrosis of dry gangrene is modified by liquifactive bacteria (saprophytic/putrefactive)
95
gas gangrene
clostridial infections with gas production - need low oxygen tension appears dark red to black and smells
96
fat necrosis
due to inflammation such as pancreatitis with leakage of lipase's, saponification, fatty acids combine with Ca, firm to hard, basophilic calcium deposits + inflammatory cells
97
fibrinoid vascular necrosis
Ag:Ab deposition in small artery walls, activates complement, leading to necrosis of vessel wall, deposition of fibrin after damage of endothelial cells with leakage of plasma proteins into vessel wall
98
metaplasia
one type of cell is replaced by another more able to withstand an adverse environment - reversible
99
difference between simply and numeric atrophy?
simple atrophy is shrinkage of cells due to loss of cell substance, numeric atrophy is loss of cells
100
what stimulates and opposes the ubiquitin proteasome path?
glucocorticoids, thyroid hormone stimulate | insulin opposes
101
autophagic vacuoles
membrane bound vacuoles within the cell that contain fragments of cell components destined for destruction - occurs during atrophy
102
pathologic atrophy examples
disuse, denervation, diminished blood supply, inadequate nutrition, aging
103
2 mechanisms of atrophy
lysosomal acid hydrolyses and ubiquitin proteasome path
104
cause of hypertrophy
synthesis of more structural components in on dividing cells
105
What is the distinguishing feature between hyperplasia and neoplasia?
In hyperplasia, cells are still under cell cycle control but not in neoplasia - hyperplasia can turn into neoplasia however
106
autophagy
lysosomal digestion of the cell's own damaged components such as organelles
107
What pair is needed for initiation of autophagia?
Beclin-1 protein + PI3K
108
What does the Beclin-1/PI3K protein pair do?
recruit proteins and lipids required for autophagosome formation
109
Define heterophagy
lysosomal digestion of materials ingested from extracellular environment
110
2 types of heterophagy
phagocytosis (uptake of particulate matter) and pinocytosis (uptake of soluble smaller macromolecules)
111
Accumulation of substances can occur due to these 3 things?
1) rate of metabolism is inadequate to remove it 2) defects in metabolism, packagin, transport, or secretion 3) abnormal substance deposited and cell doesn't have the enzymes to remove it
112
steatosis
abnormal accumulations of triglycerides w/in parenchymal cells
113
True/False: Fatty change is irreversible.
False, it is reversible
114
What is the accumulation of fat within the cytoplasm called? (this typically occurs in hepatocytes)
Fatty Change
115
True/False: a high carbohydrate diet can cause fatty liver in feedlot cattle.
True!
116
Starvation or __________ can cause fatty acid mobilization.
Cachexia
117
What hormone reduces blood glucose, increases blood glucose uptake, increases glycolysis and glycogenesis, and inhibits gluconeogenesis in liver?
Insulin
118
What two hormones counteract some of insulin's effects?
glucagon and cortisol
119
Diabetes Mellitis
lack of insulin or reduced insulin sensitivity of target cells
120
mallory body
protein droplets in hepatocytes due to toxin exposure
121
calcinosis circumscripta
calcification of damaged collagen fibers
122
cacinosis cutis
with natural and iatrogenic Cusing's disease
123
Two types of Pathologic Calcification
1) Dystrophic 2) metastatic
124
wear and tear pigment
occurs in mature animals due to accumulation of partially degraded cell membrane lipid and proteins in autophagic vacuoles
125
hemosiderin
brown (iron containing pigment) - degradation product of hemoglobin Indicates previous hemorrhage
126
Hematin
degradation product of hemoglobin - occurs when hemoglobin is exposed to acid such as from a gastric ulcer
127
Hematoidin
breakdown product of hemoglobin - does not conatin iron
128
Explain the process of bruising.
hemoglobin --> heme, iron, and glob in --> verdoglobin --> biliverdin (blue green) --> bilirubin