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Bailey and Love + Sabiston 20e > Metabolic Response to Injury > Flashcards

Metabolic Response to Injury Flashcards

1
Q

The term Homeostasis was given by

A. Claude Bernard
B. Walter Canon
C. John Hunter
D. Halstead

A

Ans B -

homeostasis : the coordinated physiologic process which maintains most of the steady states of the organism was a definition given by Walter Cannon.

Claude Bernard - the stability of “Milieu Interieur” is the primary condition for freedom and independence of existence.

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2
Q

which of the following statements is not true regarding metabolic response to injury

A. Reponse to injury is graded
B. Response to injury is always dose dependent
C. Genetic variability plays a key role in determining the intensity of response
D. Metabolic response evolves with time.

A

Ans B -

Response to injury is graded - more severe the injury, greater the response.

In certain circumstances the severity of injury does not lead to a simple dose dependent metabolic response but rather leads to quantitatively different response.

Genetic variability plays a key role in determining the intensity of inflammatory response.

Not only is the metabolic response graded but it also evolves with time, from a pro-inflammatory state driven by innate immune system (Macrophages, neutrophils, dendritic cells) into a compensatory anti-inflammatory response syndrome.

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3
Q

All of the following are counter-regulatory hormones except -

A. Glucagon
B. Thyrotropin
C. Cortisol
D. Adrenaline

A

Ans B -

CRF released from hypothalamus increases ACTH, which in turn causes release of cortisol.
Hypothalamic activation of sympathatetic nervous system causes release of adrenaline and also stimulates the release of glucagon.

Iv infusion of these counter-regulatory hormones - Glucagon, Glucocorticoids and Catecholamines - reproduces many aspects of metabolic response to injury.

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4
Q

All of the following are decreased within first 24-48 hours of surgical injury except

A. Insulin
B. IGF-1
C. Testosterone
D. GH

A

Ans D -

Integrated response to surgical injury during the first 24-48 hours.

Increased -
ACTH, Adrenaline, Cortisol, Glucagon, GH.
IL-1, TNF-alpha, IL-6, IL-8

Decreased -
Insulin, IGF-1, Testosterone, T3.

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5
Q

Which of the following is not seen during first 24-48 hours of surgical injury

A. Increased skeletal muscle protein degradation
B. Pyrexia
C. Hepatic Lipolysis
D. Hepatic Acute Phase protein synthesis
E. Hypermetabolism
A

Ans C -

Changes in body metabolism that are seen within the first 24-48 hours of surgical injury include -

Adipocyte Lipolysis, Hepatic Gluconeogenesis, Skeletal muscle Protein degradation, Pyrexia and Hypermetabolism.

There is increased synthesis of hepatic acute phase proteins.

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6
Q

Which of the following is not involved in the development of Th2 type response to injury

A. IL-13
B. IL-4
C. IL-8
D. TGF-Beta

A

Ans C -

A complex series of adaptive changes includes the development of Th2 type counterinflammatory response regulated by IL-4, IL-5, IL-9 and IL-13 and TGF-Beta. This response if accentuated and prolonged in critical illness is characterised as CARS.

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7
Q

CARS stands for -

A. Chronic Anti-Inflammatory response syndrome
B. Compensatory Anti-Inflammatory Response syndrome
C. Counter-Adaptive response syndrome
D. Chronic Adaptive Response syndrome

A

Ans B -

Compensatory anti-inflammatory response syndrome or CARS is characterised by suppressed immunity and diminished resistance to infection.

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8
Q

All of the following are systemic inflammatory antagonists except -

A. IL-1Ra
B. TNF-sR-55
C. TNF-sR-75
D. Protectins

A

Ans D -

Within hours of upregulation of proinflammatory cytokines, endogenous cytokine antagonists enter the circulation e.g. Interleukin -1 receptor antagonist [IL-1Ra] and TNF soluble receptors TNF-sR-55 and TNF-sR-75.

Within the inflammed tissue, the duration and magnitude of acute inflammation as well as the return to homeostasis are influenced by a group of local mediators known as specialized pro-resolving mediators - which include

  • Essential fatty acid derived Lipoxins
  • Resolvins
  • Protectins
  • Maresins.

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9
Q

The Natural response to injury includes all of the following except -

A. Immobility
B. Anorexia
C. Pyrexia
D. Catabolism

A

Ans C -

In the natural world if an animal is injured it displays a characteristic response which includes -

  • Immobility or Rest
  • Anorexia
  • Catabolism

These changes are designed to aid survival of moderate injury in the absence of medical intervention.

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10
Q

which of the following statements is true regarding the ebb and flow model

A. It was proposed by John Hunter

B. Ebb phase can be completely abolished by adequate and timely resuscitation

C. Ebb phase lasts for 24-48 hours

D. Glucagon is one of the predominant hormones regulating the ebb phase

A

Ans C -

Sir David Cuthbertson divided the metabolic response to injury into the ‘ebb’ and ‘flow’ phases.

Ebb phase begins at the time of injury and lasts for approximately 24-48 hours.

Ebb Phase can be attenuated by proper resuscitation but it cannot be completely abolished.

Ebb phase is characterized by Hypovolemia, decreased BMR, decreased Cardiac Output, Hypothermia and Lactic Acidosis.

The predominant hormones regulating the ebb phase are catecholamines, cortisol and aldosterone.

The magnitude of this neuroendocrine response depends on the degree of blood loss and the stimulation of somatic afferent nerves at the site of injury.

Main physiological role of the ebb phase is to conserve both the circulating volume and energy stores for recovery and repair.

Following resuscitation, the ebb phase evolves into a hypermetabolic flow phase which corresponds to SIRS.

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11
Q

Which of the following is not a feature of ebb phase

A. Hypovolemia
B. Pyrexia
C. Decreased BMR
D. Decreased cardiac output
E. Lactic Acidosis
A

Ans B -

The ebb phase is characterised by hypovolemia, decreased BMR, Decreased cardiac output, hypothermia and lactic acidosis.

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12
Q

The flow phase is characterised by all of the following except

A. Rise in the level of counter-regulatory hormones - insulin, glucagon, cortisol and adrenaline

B. Increased BMR and body temperature.

C. Increased levels of IL-4, IL-5 and TGF-Beta.

D. Significant insulin resistance.

A

Ans C-

The flow phase correponds to SIRS. Involves mobilisation of body energy stores for recovery and repair.

Characterised by

  • tissue edema (Vasodilation, capillary leakage)
  • increased BMR
  • Increased Cardiac Output
  • Raised Body temperature
  • Leukocytosis
  • increased Oxygen consumption
  • increased Gluconeogenesis.

The flow phase can be subdivided into initial catabolic phase (3-10 days) and anabolic phase lasting for weeks.

During the catabolic phase there is increased production of counter-regulatory hormones - catecholamines, insulin, cortisol, glucagon and inflammatory cytokines (IL-1, IL-6 and TNF-alpha)

The increased production of insulin at this time is associated with significant insulin resistance and therefore, injured patients often exhibit poor glycemic control.

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13
Q

Majority of trauma patients demonstrate energy expenditure ____% above predicted healthy values

A. 5-10%
B. 15-25%
C. 25-40%
D. 40-50%

A

Ans B -

Majority of trauma patients except possibly those with excessive burns, demonstrate energy expenditures approximately 15-25% above predicted healthy resting values.

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14
Q

which of the following muscles is spared during catabolic response to injury

A. Peripheral Skeletal Muscle
B. Cardiac Muscle
C. Gut
D. Respiratory Muscle

A

Ans B -

During the catabolic phase of metabolic response to injury muscle wasting occurs as a result of increased muscle protein degradation coupled with decreased muscle protein synthesis. (There is increased efflux of glutamine and alanine from muscle and this is derived in part from the irreversible degradation of the branches chain amino acids.)

The major site of protein loss is the peripheral skeletal muscle. Nitrogen losses also occur in respiratory muscles (leading to hypoventilation and chest infections) and in the gut (reducing the gut motility). Cardiac muscles appear to be mostly spared.

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15
Q

which of the following statements is false regarding catabolic phase

A. Upto 500g of skeletal muscle can be lost per day in major sepsis.

B. Hyperalimentation to replace the energy and protein losses is recommended.

C. Normally, muscle protein synthesis is depressed during excercise.

D. ATP-dependent Ubiquitin proteasome pathway is the predominant mechanism involved in wasting of skeletal muscle.

A

Ans B -

Muscle protein turnover rate in humans in normal circumstances - 1-2% per day.

Paradoxically during excercise, skeletal muscle synthesis is depressed, but it increases again during rest and feeding.

Under extreme conditions such as major sepsis, urinary nitrogen losses can reach upto 14-20 g/day and this equals loss of 500g of skeletal muscle per day.

Muscle catabolism cannot be inhibited fully by providing artificial nutritional support. In critical care it is now recognized that hyperalimentation represents a metabolic stress in itself, and that nutritional support should be at a modest level to attenuate rather than replace energy and protein losses.

The predominant mechanism involved in muscle wasting is the ATP dependent ubiquitin-proteasome-pathway.

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16
Q

Which of the following is correctly matched with respect to ATP-dependent ubiquitin proteasome pathway

A. E1 - Ubiquitin Activating enzyme
B. E2 - ubiquitin conjugating enzyme
C. E3 - ubiquitin Ligase
D. All of the above

A

Ans D -

This is the intercellular effector mechanism involved in degrading myofibrillar protein into free amino acids.

It requires ATP.
Depends on the 26s Proteasome, Caspases, Cathepsins and Calpains.

E1 - Ubiquitin Activating enzyme
E2 - Ubiquitin Conjugating enzyme
E3 - Ubiquitin ligase

B&L 27e Pg 7 Fig 1.6

17
Q

What is the normal muscle protein turnover rate in humans

A. 1-2%
B. 2-5%
C. 5-10%
D. 10-12%

A

Ans A -

The liver and skeletal muscle account for >50% of the daily body protein turnover. Skeletal muscle has a large mass but a low turnover rate of 1-2%. Whereas liver has a small mass (1.5kg) and a higher protein turnover rate of 10-20% per day.

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18
Q

What is the albumin renewal rate in human body

A. 2% per day
B. 5% per day
C. 10% per day
D. 15% per day

A

Ans C -

Hepatic protein synthesis is divided roughly 50-50 between -

  • renewal of structural proteins
  • synthesis of export proteins

Albumin is the major export protein produced by the liver and it is renewed at the rate of 10% per day.

The transcapillary escape rate of albumin is however 10 times the rate of synthesis, and short term changes in the albumin concentration are most likely due to increased vascular permeability. Albumin TER may be increased 3-fold following major injury/sepsis.

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19
Q

Which of the following is the major promoter of hepatic acute phase protein synthesis

A. IL-1
B. IL-6
C. IL-8
D. TNF-alpha

A

Ans B - IL-6

In response to inflammatory conditions a range of proinflammatory cytokines including IL-1, IL-6 and TNF-alpha are secreted. These cytokines, in particular IL-6 promote the hepatic synthesis of acute phase proteins such as Fibrinogen, and CRP.

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20
Q

Which of the following is predominant cause for decrease in the concentration of negative acute phase reactants

A. Capillary leak
B. Urinary Loss
C. Increased breakdown
D. Decreased synthesis

A

Ans A -

In contrast to positive acute phase reactants, the plasma concentration of other liver export proteins (negative acute phase reactants) fall acutely following injury - eg. Albumin.

However, rather than representing a reduced hepatic synthesis rate, the fall in plasma concentration of negative acute phase reactant is though to reflect increased transcapillary escape secondary to increased microvascular permeability.

Therefore the increased synthesis of positive acute phase reactants is not compensated by decreased synthesis of negative acute phase proteins but rather increased breakdown of peripheral skeletal muscle proteins.

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21
Q

what percentage of the total body mass is composed of water?

A. 20%
B. 40%
C. 60%
D. 80%

A

Ans C -

The average 70 kg man contains about 13 kg fat (nearly 20%) and 57 kg lean body mass.

The lean tissue is composed of 12 kg Protein, 42 kg water and 3kg minerals.

42kg water means 60% of the total body weight.

The protein is divided into skeletal muscle 4 kg and non-skeletal muscle 8 kg.

The water mass is divided into intracellular 28 kg, and extracellular 14 kg.

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22
Q

What percentage of the total body protein is stored in the skeletal muscle

A. 33%
B. 66%
C. 75%
D. 25%

A

Ans A - 33%

The total protein mass in a 70 kg male is nearly 12 kg. Out of this one third is skeletal muscle mass (4kg) and two thirds is non-skeletal muscle mass (8kg)

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23
Q

What percentage of the total body weight is composed of intracellular water?

A. 20%
B. 40%
C. 60%
D. 80%

A

Ans B -

Nearly 60% of the total body weight is composed of water - 42kg out of 70 kg.
Out of this nearly 2/3 (28 kg) is stored intracellular whereas 1/3 (14 kg) is stored extracellular.
Therefore 40% of the total body weight is composed of intracellular water.

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24
Q

What percentage of the total body weight is composed of minerals?

A. <5%
B. 5-10%
C. 10-15%
D. 15-20%

A

Ans A -

Minerals make up about 3kg of the body weight in a 70 kg man and therefore they consist of nearly 4.2% of the total body weight.

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25
Q

Which of the following is not true regarding insulin resistance seen after surgery or trauma?

A. Behaves similar to DM type II.

B. Proportional to the magnitude of the injurious process

C. Usually resolves in 2 days-3 days.

D. None of the above

A

Ans C -

Post operative hyperglycemia develops as a result of increased glucose production combined with decreased glucose uptake.

Suggested mechanism include the action of proinflammatory cytokines and decreased responsiveness of insulin regulated glucose transporter proteins.

The degree of insulin resistance is proportional to the magnitude of the injurious process.

Following routine upper abdominal surgery insulin resistance may persist for nearly 2 weeks.

Behave in a similar manner to type II diabetes mellitus. The mainstay of management is iv insulin infusion. It can used in the intensive sliding scale approach or a conservative approach (administer when blood glucose crosses a defined limit)

The risks of adverse events following significant hypoglycemia as a consequence of intensive insulin therapy have led most ICUs to adopt a more conventional approach to glycemic control.

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26
Q

1g of nitrogen corresponds to _____g of wet weight tissue.

A. 6.25g
B. 18g
C. 36g
D. 60g

A

Ans C -

Each 1g of nitrogen is contained within 6.25g of protein , which is contained in approximately 36g of wet weight tissue.
Thus the loss of 1g of nitrogen in urine is equivalent to breakdown of 36g of wet weight lean tissue.

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27
Q

Normal urinary loss of nitrogen per day is

A. 7g/day
B. 14g/day
C. 21g/day
D. 10g/day

A

Ans B -

Protein turnover in the whole body is of the order of 150-200g per day. A normal human ingests 70-100g of protein per day, which is metabolised and excreted in urine as ammonia and urea i.e. approximately 14g per day of Nitrogen.

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28
Q

Survival is unlikely if loss of body protein reaches ____% of total

A. 10-20%
B. 30-40%
C. 40-50%
D. >50%

A

ANS B -

During total starvation, urinary loss of nitrogen is rapidly attenuated by a series of adaptive changes. Following major injury, and particularly after severe sepsis, this adaptive change fails to occur and there is a state of autocanabilism which results in continued urinary nitrogen loss of 10-20g per day (nearly 500g of wet weight lean tissue per day)

Once loss of body protein reaches 30-40% of the total, survival is unlikely.

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29
Q

In critically ill patients, ____% of total body protein loss is expected even with optimum metabolic care and nutritional support -

A. 5%
B. 15%
C. 20%
D. 25%

A

Ans B -

Critically ill patients admitted to the ICU with severe sepsis or major blunt trauma undergo massive changes in body composition. Body weight increases immediately on resuscitation with an expansion of extra-cellular water by 6-10 litres within 24 hours. Thereafter even with optimal metabolic care and nutritional support, total body protein will diminish by 15% in the next 10 days.

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Bailey and Love + Sabiston 20e (4 decks)

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