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Integrative Phys > Subcellular level of Injury > Flashcards

Subcellular level of Injury Flashcards

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1
Q

What are the major functions of lysosomes?

A
  • Turn over of cellular constituents
  • Nutrient sensing via mTORC1 recruitment to promote anabolism
  • Calcium storage
  • Calcium signalling
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2
Q

How do lysosomes turn over cellular constituents?

A
  • Endocytosis, phagocytosis, autophagy
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3
Q

What is calcium signalling important for?

A
  • Lysosomal acidification
  • Fusion with other organelles
  • Membrane trafficking and repair
  • Autophagy
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4
Q

How can indigestible material interact with lysosomes?

A
  • Exogenous or endogenous materials may persist in lysosomes as residual bodies
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5
Q

What is the outcome of endogenous material interacting with lysosomes?

A
  • Lipofuscin
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6
Q

What is lipofuscin? What can lipofuscin be made up of?

A
  • Auto fluorescent lipopigment

- Highly cross-linked, undegradable protein that aggregates lipids, carbohydrates, and metals

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7
Q

What is lipofuscin known as?

A
  • The wear-and-tear pigment
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8
Q

Why is lipofuscin formed?

A
  • ROS and oxidative stress
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9
Q

How can oxidative stress and aging be detected due to lipofuscin?

A
  • The gradual accumulation of lipofuscin in neurons, retinal pigment, epithelium, cardiac myocytes, and muscles cells
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10
Q

What are the major components of lysosomes? (3)

A
  1. Luminal proteins
  2. Integral membrane proteins
  3. Lysosomal-associated proteins (LAMPs)
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11
Q

What is the purpose of luminal proteins in lysosomes?

A
  • This is where acid hydrolases or their activators for enzymes reside
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12
Q

What fits in the category of integral membrane proteins in lysosomes?

A
  • Structural amino acids and lipid transporters
  • Ion-channels
  • Trafficking and fusion machinery
  • Membrane catabolic enzymes
  • Vesicular ATPase to sense acidity
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13
Q

What is LSD? What is it classified by?

A
  • Lysosomal Storage Disease

- Inborn errors of metabolism

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14
Q

What are two “kinds” of LSDs?

A
  • Caused by enzyme defects

- Caused by defects in enzyme activates or associated proteins

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15
Q

What are the most common forms of LSDs?

A
  • Fabry
  • Gaucher
  • Metachromatic leukodystrophy
  • Pompe
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16
Q
  • What do Fabry and Gaucher disorders have in common?
A
  • Characterized by the accumulation of glycolipids
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17
Q

What is metachromatic leukodystrophy?

A
  • Destroyed white matter in the CNS
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18
Q

What is Pompe characterized by? Why does this happen?

A
  • A glycogen storage disease

- Enzymes (GAA-acid alpha-glucosidase) are not breaking down glycogen, and it builds up

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19
Q

What is most affected by Pompe?

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A
  • Cardiac and skeletal muscle
20
Q

What is the pathogenesis of Pompe?

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A
  • Lysosomal enlargement leads to eventual rupture

- Process of autophagy is impaired

21
Q

What does the impairment of autophagy in Pompe lead to?

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A
  • An abundance of proteins building up in the cell
22
Q

What is Chediak-Higashi syndrome (CHS) in the cytoskeleton caused by?

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A
  • A defect in the LYST gene product
23
Q

What does a normally functioning LYST gene product do?

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A
  • Sorts endosomal protein into late multi-vesicular endosomes via a mechanism involving microtubules
24
Q

Defects in LYST affect storage and secretory functions of what?

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A
  • Lysosomal granules or leukocytes, fibroblasts, or platelet dense granules (all lysosomal related organelles)
  • Azurophilic granules of neutrophils
  • Melanosomes of melanocytes
25
What do the affected storage and secretory functions lead to?
- Causes enlargement of vesicles and non-functional lysosomes
26
What kind of disorder is Kartagner's syndrome in the cytoskeleton?
- A ciliary disorder
27
What are typical symptoms of Kartagner's syndrome?
- Situs Inversus (heart on wrong side) - Sinusitis - Bronchiolectasias (congestion of bronchioles causing difficulty breathing)
28
What is the particular defect of the cilia in Kartagner's syndrome?
- The outer dynein arm is missing
29
What is the outer dynein arm useful for in the respiratory tract when working properly?
- Acts to clean a normal cell | - Not working = chronic infection
30
What defect characterizes muscular dystrophy in the cytoskeleton?
- A defect in the DMD gene | - Provides instructions for making dystrophin
31
What is dystrophin? What does it do? What happens when it is no longer functional?
- The largest human gene - Attaches microfilaments to protein - We lose stability when it is damaged
32
What does the accumulation of intermediate filaments cause?
- The formation of Mallory bodies
33
What causes neurofibrillary tangles?
- Destabilized microtubules which will become hyperphosphorylated to form paired helical filaments (PHF)
34
What determines amyloid plaque formation?
- If amyloid precursor protein (APP) is cleaved by alpha-secretase, plaque is not formed - If APP is cleaved by beta-secretase, amyloid-beta forms and sticks together to create a plaque
35
What are neuritic plaques?
- Degenerating axons and neurites
36
What may be an adaptive change in the liver SER in response to prolonged barbiturate use?
- Hypertrophy of the liver SER
37
How are barbiturates modified by the liver?
- Modified by oxidative demethylation
38
What does oxidative demethylation of barbiturates do within the SER?
- Increases the solubility of compounds, such as alcohol and steroids - Facilitates secretion
39
What are the 4 mitochondrial changes that can occur due to metabolic disturbances?
1. Megamitochondria 2. Alterations in number 3. Myopathies 4. Oncocytoma
40
In what conditions is megamitochondria seen?
- Alcoholic liver disease | - Nutritional deficiency
41
What is megamitochondria characterized by? What is produced?
- An enlargement of the space between cristae | - Both ATP and ROS are produced
42
What are myopathies?
- Mitochondria have abnormal crista
43
What may myopathies disrupt? Why?
- The ETC | - Because the abnormal cristae, where ETC takes place, are dysfunctional
44
What does oncocytoma cause?
- Mitochondrial hyperplasia
45
Where does oncocytoma typically occur?
- Salivary glands - Thyroid - Kidney
46
What is oncocytoma exactly?
- A benign tumour made up of oncocytes
47
What are oncocytes?
- Epithelial cells characterized y excessive amount of mitochondria

Integrative Phys (5 decks)

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