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Cardiovascular System > ROS, ischemia and apoptosis > Flashcards

ROS, ischemia and apoptosis Flashcards

1
Q

How are ROS made?

A

Partial reduction of oxygen

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2
Q

Superoxide radical

A

O2.-

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3
Q

Hydroxyl radicals

A

OH.

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4
Q

Hypochlorous acid

A

HOCL

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5
Q

How are RNS formed?

A

reaction of superoxide with NO

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6
Q

Peroxynitrite

A

ONOO-

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7
Q

Is NO reactive?

A

No but the intermediates are

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8
Q

Symptoms of too many RNS

A

Ischemia, IBD, arthritis

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9
Q

Why is NO a co-oxidant?

A

reacts with super-oxide to form peroxynitrite which is cytotoxic to tissues, generated at inflammation

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10
Q

Why are ROS bad?

A

At high levels = mitochondrial dysfunction

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11
Q

When are RNS produced?

A

Metabolic byproducts of inflammatory diseases

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12
Q

How is hydrogen peroxide formed

A

Dismutation of O2.-

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13
Q

Where are free radicals made?

A

Mitochondria - outer/inner membrane and matrix

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14
Q

NADPH oxidase

A
  • Free radical generation in neutrophils and macrophages during phagocytosis releases reactive species
  • NADPH oxidases (NOX enzymes 1-5) and DUOX1 and 2 convert oxygen to superoxide
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15
Q

What is apoptosis?

A

programmed cell death

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16
Q

What is autophagy?

A

Eukaryotic cells degrade cytoplasmic material - lysosomes. Stimulated by lack of nutrients

17
Q

What is necrosis?

A

Unregulated cell death

18
Q

Apoptosis

A
  • Tightly controlled
  • Loss of intercellular junctions
  • Chromatin condenses
  • Cytoplasm shrinks
  • Components recycled
  • Phagocytosis of apoptotic bodies by neighbouring cells and macrophages
  • No release of intracellular content
  • Apoptotic bodies are phagocytosed
  • Surface markers cause cells that ingest them to secrete anti-inflammatory cytokines
  • No inflammation
19
Q

Necrosis

A
  • Results due to trauma
  • Autolysis
  • Loss of cell membrane integrity and losing cellular components into intercellular space
  • Stimulates leukocytes etc to come and destroy cells
  • Neutrophils enter site and then monocytes
  • Early necrosis is reversible
  • Oncosis - mitochondria damaged beyond recovery so no ATP made which disrupts ionic concentrations
  • Lack of cellular homeostasis - water enters cells - cell membranes and organelles swell - autodigestion - lytic enzymes destroy content - content released into extracellular space
  • Debridement removes necrotic tissue
  • Infarction
  • Coagulative necrosis - build up of fluid but architecture of tissue maintained - albumin forms firm state
20
Q

Ischemia

A
  • Occlusion of coronary artery
  • Hypoxia: oxygen supply insufficient for demand, cause is low oxygen conc, leads to pulmonary oedema and cerebral oedema
  • Ischaemia: reduction of blood supply damages oxygen sensitive tissues, caused by problems with circulatory system, leads to MI, stroke, reperfusion injury and arrythmias
  • Stops Krebs cycle = lots of lactic acid = intracellular pH falls
  • Na+/K+ pump causes influx of sodium
  • Myocardial contraction ceases within a minute of ischemia
21
Q

Reperfusion

A
  • Re-opening of coronary artery
  • Cardiomyocytes have lots of mitochondria
  • Cardiolipin - lots of unsaturated fatty acids, make compound vulnerable to peroxidation
  • NADPH oxidases in neutrophils, make lots of superoxide
  • When ischaemia tissue reperfused, influx of oxygen catalyses xanthine oxidase to degrade hypoxanthine to uric acid and releases superoxide anion
  • Hydroxide radicals = lipid peroxidation
  • Influx of calcium causes cell death by hypercontracture of heart cells
22
Q

What is PTP?

A

Depolarisation of mitochondrial membrane

23
Q

Mitochondrial permeability transition pores

A
  • PTP = depolarisation of mitochondrial membrane
  • Reverses ATP synthesis to maintain membrane potential
  • Activated fatty acids accumulate in myocardium
24
Q

Inflammation

A
  • During reperfusion, neutrophils adhere to endothelium and extravasate into tissue, resulting in degradation of basement membranes
  • Neutrophils generate ROS = tissue degradation
  • Lots of neutrophils = lots of ROS via NADPH

O2 can undergo 4 consecutive reductions

25
Q

Is NO a free radical?

A

No

26
Q

Is H2O2 a free radical?

A

Yes

Cardiovascular System (21 decks)

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