Exam 1- L1 Flashcards

(44 cards)

1
Q

What functionally happens with reversible cell injury?

A

reduced oxidative phosphorylation resulting in the depletion of energy stores

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens in cell injury when you deplete energy stores?

A
  • NA/K ATPase– ATP dependent, so sodium flows into the cell and water follows, causing cell swelling
  • Ca-ATPASE–> channel fails, increasing Ca influx, which causes amorphous densities in mitochondria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe/name reversible cell injury

A
  • Dilation of ER
  • Nuclear alterations
  • Mitochondrial changes: swelling
  • plasma membrane alterations (loss of microvilli, swelling of RER, blebbing, and blunting)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe irreversible cell injury

A
  • cell death (apoptosis and necrosis)
  • loss of membrane permeability
    amorphous densities in mitochondria
    myocardial ischemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the difference between necrosis and apoptosis?

A
  • Apoptosis: cell suicide ( no complete loss of cell membrane integrity and involves cell shrinkage…cells cleared by macrophages
  • necrosis: result from damage to cell membranes and loss of homeostasis ; leakage if lysosomal enzymes, and leakage of cellular content—> cell swelling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the electron micrograph of mitochondria with amorphous densities. Review: Why is it present?

A

Looks like a battleship smoke cloud within mitochondria
- present due to the failure of Ca-ATPase that was caused by the depletion of ATP (energy)..influx of calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Coronary artery disease can lead to ischemia due to a blockage.

Describe the course of action when blockage occurs.

A

1) fall in oxygen supply to area
2)loss of oxidative phosphorylation (ETC)..DECREASE of ATP
3) Failure of Na/K ATPase and Ca-ATPase
4) heart muscles cease to contract in 60sec of coronary occlusion
5)30-40 min later, it worsens….irreversible changes like amorphous densities in mito (calcium)
6) ca influx leads to necrosis and apoptosis–> degradation and leakage of cellular material
7) formation of myelin figures…eventually calcification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe what myocardial infarction looks like?(gross and histological)

A

gross image: pale/ white tissue
histo: cells without nuclei ( ghost outline of myocytes.. tombstones
- blue dots are inflamed cells due to leakage of cellular contents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the histological artifacts of cells undergoing apoptosis?

A
  • shrunken cells
  • retraction spaces that look like a clearing around the cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are causes of cell injury? (3) Give an example for each

A

1) hypoxia…. thrombi/occlusion
2) physical… radiation
3) chemical agents…. Tylenol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are major causes of hypoxia? How so?

A
  • cardiorespiratory failure
  • anemia –>HB= heme + globin .. heme has Fe and porphyrin ring .. if you have low iron (lower heme) .. less oxygen is delivered to the tissues
    -carbon monoxide–> carbon binds to Hb tightly… affinity switches to preferring carbon over oxygen when oxygen depletes or is at a lower level of saturation
  • after severe blood loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are examples of hypoxia? Describe how they lead to hypoxia

A
  • anemia
  • CO poisoning ( forms carboxyhemoglobin)
  • methemoglobinemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is Methemoglobinemia?

A

when heme has Fe+3 (oxidized state) instead of Fe+2….. cannot deliver oxygen or bind oxygen
- indicated as it when RBC has more than 1% methemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the difference between congenital and acquired methemoglobinemia? Treatment?

A

Congenial: NADH reductase deficiency , which decreases the rate of reduction of iron (Fe+2) in Hb
- diffuse persistent slate-gray cyanosis; patients are typically asymptomatic

Acquired: due to ingestion of drugs or toxic substances.. like sulfa containing drugs or nitrites

Treatment: methylene blue (IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is ischemia different from hypoxia?

A
  • hypoxis: energy production continues in the form of glycolysis
  • ischemia: no aerobic or anaerobic respiration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does obstruction lead to?

A

Obstruction leads to a complete lack of oxygen and substrates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

When looking at gross images, what is the difference of atherosclerosis and thrombotic occlusion?

A
  • calcification is present within blood tissue of blood vessels.. narrows the lumen
  • thrombi us within the lumen of a blood vessel…blocks the lumen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name types of physical agents that can cause cell injury

A
  • mechanical trauma
  • extremes of temps ( burns and deep cold)
    -sudden changes in ATM pressure
    -radiation
    -electric shock
19
Q

What happens with acetaminophen poisoning? What disease does it cause?

A
  • liver metabolizes and clears out all the comes in
  • liver can be overwhelmed.. leading to P450 to produce intermediates ( reactive liver metabolites), which are free radicals
  • body cannot clear out ROS, leading to cellular damage and function
  • Acute Liver Failure
20
Q

What are the mechanisms of cell injury?

21
Q

What are chemical causes of cell injury?

A

drugs
chemicals
specific example: acetaminophen

22
Q

In apoptosis, what does the leakage of cytochrome C cause?

A

leakage of cytochrome C causes the activation of executor caspases leading to apoptosis

23
Q

Describe receptor induced apoptosis

A
  • FAS and TNF binds to receptor
  • causes initiator caspases to activate
    -mitochondria leaks cytochrome C
  • leakage of cytochrome C causes the activation of executor caspases, inducing committing to apoptosis
24
Q

Describe Acute Liver Failure caused by acetaminophen
- cause
-mechanism of action of cause
-symptom
-timing

A
  • caused by massive hepatic necrosis
    -parenchymal loss surrounding the islands of regenerating hepatocytes
  • changes take place within hours to days.. not enough time to regenerate or form scar
  • symptoms: nausea, vomiting, and jaundice……..then life-threatening encephalopathy and coagulation defects
25
What are the mechanisms of cell injury? (2)
- energy (ATP) depletion - production of ROS (free radicals)
26
What are the major causes for ATP depletion?
- reduced supply of oxygen and nutrients - mitochondrial damage toxic chemicals (like cyanide)
27
What levels of ATP depletion triggers the failure of Ca-ATPase and Na/K ATPase, and oxidative phosphorylation?
Depletion of ATP to 5%-10% of normal levels
28
What happens when the cell is experiences prolonged ATP depletion?
- detachment of ER - unfolded protein response - protein synthesis shuts down - irreversible damage to mito
29
What does the influx of calcium lead to?
- caspases-- leads to apoptosis -endonuclease--> fragments DNA -proteases-- damages cell membrane - phospholipases- damages cell membrane - ATPases--> depletes ATP
30
What are the consequences of mitochondria damage?
- mito permeability, causing the leakage of cyto C.. leading to apoptosis - formation of ROS due to abnormal ETC - Activation of enzymes like proteases, endonucleases, phospholipases (A), caspases, ATPases
31
What happens to skin with exposure to sunrays?
- skin has H20 - when sunrays hit the skin, hydrolysis occurs, generating free radicals
32
What does cytokeratin intermediate filaments do? What does it mean for them to be damaged?
- give the cell shape and structure - in cytokeratin damage in hepatocytes during alcohol induced damage ( alcoholic hepatitis) shows mallory bodies
33
Alcoholic hepatitis - risk factor cardinal sign? - symptoms - Labs
- cytokeratin goes from providing structure to forming a pink spot on histological slides (bright pink) risk factors: 100g/day (heavy alcohol use) cardinal sign: rapid onset of jaundice symptoms: fever, ascites, proximal muscle loss Labs: hint..AA like alcoholic anonymous... aspartate aminotransferase and double A for twice as much -serum levels of aspartate aminotransferase is twice the upper limit of normal range - 2:1 or more with aspartate aminotransferase : alanine aminotransferase
34
Alzheimer's disease
- neurofilaments disrupted.. forming neurofibrillary tangles... which contains tau protein (hyperphosphorylated protein) - neurofilaments are normally present in axons and serve as structural support
35
what is the progression of alcoholic hepatitis?
- fatty liver to alcoholic hepatitis to cirrhosis of the liver
36
What is nonalcoholic steatohepatitis associated with?
- associated with obesity and insulin resistance - ballooned hepatocytes -steatosis -Mallory bodies -inflammation -intrasinusoidal collagen -fibrosis or cirrhosis
37
What happens if DNA damage is too severe? What are causes?
cell initiates apoptosis exposure to drugs and radiation
38
Outline the differences between reversible and irreversible cell injury
39
Recognize types of cell death and understand it's clinical relevance
40
Differentiate between hypoxia and ischemia. Explain clinical conditions for hypoxia and ischemia
41
Explain how chemicals produce cell injury using clinical examples
42
Understand the mechanisms of cellular injury identifying cell organelles that are affected
43
What are the molecular targets of ROS?
- lipids: peroxidation in membranes - proteins: oxidative modification of proteins nucleic acids: ss/dsDNA
44
What are examples of free radical injuries?
- chemical and radiation injury - liver necrosis by drugs - ischemia- reperfusion injury - retinopathy of prematurity.. increase in proliferation of retinal vessels in premature babies.... can lead to blindness if you give 100% oxygen can damage blood vessels and lead to ROS -iron overload (hemolytic anemia...accumulation of iron) -cellular aging -microbial killing by phagocytes