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Physiology > LECTURE 32 > Flashcards

LECTURE 32 Flashcards

1
Q

What is cancer cachexia?

A

Multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass with out without loss of fat mass that leads to progressive functional impairment

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2
Q

When is clinical diagnosis of cancer cachexia made?

A
  • Weight loss >5% over the past 6 months in absence of starvation
  • BMI 2%
  • Appendicular skeletal muscle index consistent with sarcopenia (M: >7.26kg/m2, F: 2%
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3
Q

What percentage of cancer patients does cachexia affect?

A

> 80%

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4
Q

What percentage of patients with pancreatic or gut cancers have cachexia?

A

80%

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5
Q

What percentage of patients with prostate, colon or lung cancers have cachexia?

A

50%

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6
Q

What groups of people is cachexia more common in?

A

Children and elderly

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7
Q

How many new cases of cancer and how many deaths per year?

A

115,000, 43,000 (most from cachexia)

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8
Q

What are the consequences of cancer cachexia that lead to reduced quality of life?

A
  • Decreased muscle function
  • Impaired mobility (40% drop in physical activity)
  • Enhanced fatigue
  • Reduced independence
  • Premature retirement
  • Increase incidence of metabolic disease
  • Increased risk of complications during surgery
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9
Q

What are the consequences of cancer cachexia that lead to death?

A

Impaired response to chemo and radiotherapy, cardiac failure, respiratory failure

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10
Q

What does C-26 injected into rats do?

A

Loss of muscle mass, spinal kyphosis and resp failure (severe has more similarities to human condition than mild)

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11
Q

What happens to mice with severe or mild cachexia after chemotherapy?

A

Severe: 42% reduction in tumour size
Mild: 82% reduction in tumour size

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12
Q

What happens to the diaphragm in cachectic mice?

A

Reduced force producing capacity, tidal volume and ventilation

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13
Q

What factors were altered in cadavers with cancer cachexia?

A

Heart mass, structural remodelling, cardiac fibrosis, systolic dysfunction (reduced ejection fraction)

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14
Q

What percentage of deaths is cancer cachexia responsible for?

A

20-30% of all cancer related deaths

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15
Q

What is muscle mass a predictor of in cancer patients?

A

Toxicity associated with chemotherapy, chance of remaining failure free after chemotherapy and survival

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16
Q

What happens with a 15% decrease in muscle mass? 25-305?

A

Reduced function, death

17
Q

What is muscle strength a predictor of?

A

Survival

18
Q

What does anorexia treatment lead to?

A

Increased food intake, but no real changes in lean body mass or quality of life

19
Q

What does cytokine treatment do?

A

May have adverse side effects, often only targets one cytokine

20
Q

What does high/low myostatin lead to?

A

High myostatin increases atrophy and low myostatin increase hypertrophy

21
Q

What happens when you use myostatin inhibitory antibody?

A

Blocks myostatin (attempt to increase hypertrophy), causes small improvements in muscle mass and function

22
Q

What is activin and what does it do?

A

Similar to myostatin (bind to same receptor) but causes greater atrophy

23
Q

What happens with treatment of sACTRIIB?

A

Prevents actin/myostatin binding - causing large improvemetns in muscle mass and function and prolonged survival

24
Q

What does Ang II do?

A

Increases muscle wasting. Increase in Ang II - atrophy, decrease AT1 (Ang II receptor) increases strength.

25
Q

How can Ang II be blocked?

A

ACE inhibitor blocks conversion of Ang I - Ang II (stopping downstream pathways leading to muscle wasting)

26
Q

What does treatment with ACE do?

A

Doesn’t improve muscle of body mass but causes large improvements in muscle function and fatigue and corrected metabolic alterations caused by cachexia

27
Q

What do varying levels of TWEAK do?

A

Increased TWEAK/Fn14 (TWEAK receptor) = atrophy

Decreased TWEAK = hypertrophy

28
Q

What does treatment with Fn14 inhibitory antibody cause?

A

Improved survival, prevented loss in body and muscle mass, increased muscle strength

29
Q

Is combination treatment better than individual?

A

Yes - treat with combination of thalidomide, carnitine, EPA and megesterol for best results

30
Q

What happens to tumour bearing patients who exercise?

A

Increased muscle protein synthesis, decreased body weight, food intake and hematocrit

31
Q

Is high BMI in chronic disease good?

A

Yes - higher weight = reduction in the chance of death

Physiology (12 decks)

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