Metabolic response to sepsis, injury and starvation

Question 1

Simple starvation occurs 4-6 hours following meal, often described as phase 1 of starvation. Although lean tissue is conserved here, which of the following occurs?

1 - glycogenolysis and gluconeogenesis increases
2 - insulin resistance and gluconeogenesis
3 - proteolysis produces gluconeogenic amino acids
4 - ketones are produced from stored fat and glycogen stored are depleted

Answer 1

1 - glycogenolysis and gluconeogenesis increases

glycogenolysis = glycogen breakdown
gluconeogenesis = ATP from non-carbon sources

Question 2

Phase 2 of starvation occurs 12-18 hours following meal. Here the body does what to provide energy?

1 - glycogenolysis and gluconeogenesis increases
2 - insulin resistance and gluconeogenesis
3 - proteolysis produces gluconeogenic amino acids
4 - ketones are produced from stored fat and glycogen stored are depleted

Answer 2

4 - ketones are produced from stored fat and glycogen stored are depleted

• fat becomes the main energy source

Question 3

Mild ketosis is the physiological response to phase 2 fasting (aprox 12-18 hours since last meal). What is mild ketosis?

1 - insulin sensitivity is increased producing ketones
2 - glycogen is degraded producing ketones
3 - liver generates fat from ketone stores
4 - liver generates ketones from fat stores

Answer 3

4 - liver generates ketones from fat stores

• glucose is not essentially here as ketones are used from fat

Question 4

Mild ketosis is the physiological response to phase 2 fasting (aprox 12-18 hours since last meal). This is called mild ketosis. What are the 3 main ketones?

1 - β-hydroxy butyrate, acetone and acetic acid
2 - β-hydroxy butyrate, acetone and acetoacetate
3 - butyric acid, acetone and acetoacetate
4 - acetic acid, β-hydroxy butyrate and acetoacetate

Answer 4

2 - β-hydroxy butyrate, acetone and acetoacetate

Question 5

During phase 2 fasting (aprox 12-18 hours since last meal). The liver produces ketones from fat as an energy source, which is a physiological response called mild ketosis. This produces the 3 main ketones β-hydroxy butyrate, acetone and acetoacetate. During this time the bicarbonate (HCO3-) levels fall. Why is this?

1 - ketones damage kidneys and unable to retain HCO3-
2 - ketones cause metabolic alkalosis and HCO3- buffers
3 - ketones cause metabolic acidosis and HCO3- butters

Answer 5

3 - ketones cause metabolic acidosis and HCO3- butters

• normal HCO3- = 22-26mmol/L
• mild ketosis HCO3- = 7-8 mmol/L

Question 6

During phase 2 fasting (aprox 12-18 hours since last meal). The liver produces ketones from fat as an energy source, which is a physiological response called mild ketosis. This produces the 3 main ketones β-hydroxy butyrate, acetone and acetoacetate. What would the ketone levels be after a 12hour fast?

1 - ~ 5 mmol/L
2 - ~ 8-10mmol/L
3 - ~ 1mmol/L
4 - ~ 20mmol/L

Answer 6

3 - ~ 1mmol/L

Question 7

During phase 2 fasting (aprox 12-18 hours since last meal). The liver produces ketones from fat as an energy source, which is a physiological response called mild ketosis. This produces the 3 main ketones β-hydroxy butyrate, acetone and acetoacetate. The ketone levels after a 12hour fast would be ~ 1mmol/L. What might we see after a 20 day fast?

1 - ~ 5 mmol/L
2 - ~ 8-10mmol/L
3 - ~ 1mmol/L
4 - ~ 20mmol/L

Answer 7

2 - ~ 8-10mmol/L

Question 8

Starvation phase 3 is the final phase of starvation. Which of the following occurs?

1 - glycogenolysis and gluconeogenesis increases
2 - insulin resistance and gluconeogenesis
3 - proteolysis produces gluconeogenic amino acids
4 - ketones are produced from stored fat and glycogen stored are depleted

Answer 8

3 - proteolysis produces gluconeogenic amino acids

Question 9

Starvation phase 3 is the final phase of starvation where catabolic proteolysis occurs producing gluconeogenic amino acids. The muscles, liver and spleen are targeted before the brain and heart, but roughly what % of muscle, liver and spleen is lost during this phase?

1 - 10%
2 - 30%
3 - 50%
4 - 90%

Answer 9

3 - 50%

Question 10

During phase 3 of starvation, catabolic weight loss, what happens to the bodies wound healing, immune response, GI integrity, mobility, mental state and energy?

Answer 10

• all decrease

Question 11

Is ketosis always a bad thing?

Answer 11

• no
• good for T2DM, weight loss and epilepsy as examples

Question 12

What happens to the glucose, insulin and glucagon during ketosis?

Answer 12

• low glucose = no glucose available, so fat is used
• low insulin = inhibited by glucagon
• high glucagon = inhibits insulin

Question 13

What affect do ketones have on lipolysis?

Answer 13

• ketones inhibit lipolysis
• initially lipolysis increased to release FFA from TAG
• as ketones increase b-hydroxy butyrate provides a negative feedback inhibiting lipolysis
• this ensures the patient doesn’t go into ketoacidosis during starvation

Question 14

What are the 2 main hormones that drive ketosis during starvation?

1 - T4 and cortisol
2 - epinephrine and T3
3 - IGF and cortisol
4 - epinephrine and cortisol

Answer 14

4 - epinephrine and cortisol

Question 15

Starvation can cause a decrease in metabolic rate. Does the metabolic rate during an injury increase or decrease?

Answer 15

• increase
• body needs energy to repair itself

Question 16

What happens to blood glucose utilisation and blood glucose levels during injury?

Answer 16

• both increase
• tissues need energy to repair

Question 17

Starvation can cause an increase in gluconeogenesis. What happens to gluconeogenesis during injury?

Answer 17

• increased
• body tries to get as much energy as possible for repair

Question 18

During starvation protein catabolism and urinary nitrogen (breakdown product of amino acid oxidation) are low, but what happens during injury?

Answer 18

• catabolism is increased
• urinary nitrogen is increased
• in starvation the body tries to preserve muscle mass, but in injury there is so much tissue damage

Question 19

During starvation fat catabolism and ketone utilisation are high as the body tries to make energy. But what happens during injury?

Answer 19

• fat catabolism and ketone utilisation are low
• takes too long to produce energy
• glucose is the primary energy source needed

Question 20

In starvation weight loss is slow, is there any weight loss during injury?

Answer 20

• rapid weight loss

Question 21

What is Systemic Inflammatory Response Syndrome (SIRS)?

1 - organ dysfunction due to an infection
2 - exaggerated immune response causing systemic inflammation
3 - systemic inflammation due to an infection
4 - systemic inflammation leading to septic shock

Answer 21

2 - exaggerated immune response causing systemic inflammation
- SIRs affects temperature, pulse, and respirations
- sepsis affects multiple body systems, such as the brain, kidneys, lungs, liver, and compounding diseases the patient already has

Question 22

Systemic Inflammatory Response Syndrome (SIRS) is when there is an exaggerated immune response causing systemic inflammation, which DOES NOT need to be due to an infection. The criteria for SIRS is:

Temp >38C or <36C
HR > >90 beats/min
RR >20 breaths/min
WCC > 12/mm3 or < 4/mm3

How many of these criteria need to be met for a diagnosis of SIRS?

1 - 1
2 - 2
3 - 2 or more
4 - all of them

Answer 22

3 - 2 or more

Question 23

During starvation the energy expenditure levels drop below normal levels to maintain normal physiological states. Place the following in order of largest energy expenditure above level for normal physiological homeostasis:

• elective surgery
• -

Question 24

During starvation the energy expenditure levels drop below normal levels to maintain normal physiological states. Place the following in order of largest energy expenditure above level for normal physiological homeostasis:

• elective surgery
• major burns
• multi trauma
• skeletal trauma
• sepsis
• closed head trauma

Answer 24

1st = - major burns
2nd = multi trauma and skeletal trauma
3rd = closed head injury
4th = sepsis
5th = elective surgery

Question 25

It is clear that during times of stress of injury that the body requires additional calories. In recent research what is the optimal % of additional calories on top of the patients resting energy expenditure that was shown to reduce mortality in critically unwell patients? 1 - 10% 2 - 30% 3 - 50% 4 - 70%

Answer 25

4 - 70% - under feeding increases mortality rates

Question 26

During times of stress the body enters a hyper-metabolic state in order to acquire calories. What happens to the insulin response? 1 - increased insulin sensitivity 2 - decreased insulin sensitivity 3 - increases insulin production 4 - decreased insulin production

Answer 26

2 - decreased insulin sensitivity - stress hormones glucagon, cortisol, noradrenaline all encourage glucose, so we don't want insulin to work as well

Question 27

During times of stress the body enters a hyper-metabolic state in order to acquire calories. Generally there is insulin resistance. Changes in the insulin-signalling pathway and GLUT-4 translocation cause what to happen to skeletal muscle and adipose tissue peripherally? 1 - increased insulin sensitivity and glucose uptake 2 - decreased insulin production and insulin resistance 3 - increases insulin production 4 - decreased insulin sensitivity and glucose uptake

Answer 27

4 - decreased insulin sensitivity and glucose uptake - basically causes insulin resistance

Question 28

During times of injury of stress their is insulin resistance, meaning gluconeogenesis is the primary supply of energy. Lipolysis is generally increased, but what effect do inflammatory pathways in stress of injury do to lipolysis?

Answer 28

- reduce bodies ability to use fat as energy - takes to long as the body needs glucose quickly

Question 29

During times of injury of stress their is insulin resistance, meaning gluconeogenesis is the primary supply of energy. What is the primary energy source for gluconeogenesis during this time of stress and/or injury? 1 - lipolysis from adipose tissue 2 - proteolysis from skeletal muscle 3 - glycolysis from the liver 4 - glycogenolysis (breakdown of glycogen in the liver)

Answer 29

2 - proteolysis from skeletal muscle - ability to increase glycolysis and lactate production is associated with improved survival

Question 30

In the muscle anaerobic metabolism (lack of O2) is possible to ensure continuation of muscle contraction. What is the final end byproduct of this that enters the bloodstream? 1 - pyruvate 2 - lactate 3 - potassium 4 - NAD+

Answer 30

2 - lactate - pyruvate is converted into lactate by lactate dehydrogenase

Question 31

In the muscle anaerobic metabolism (lack of O2) is possible to ensure continuation of muscle contraction. The final end byproduct of this that enters the bloodstream is lactate, which can cause damage to the muscles when in high levels as this is an acid. Is lactate always bad then?

Answer 31

- no - converting pyruvate to lactate creates NAD+ which can be used in glycolysis - lactate can also be recycled into pyruvate by lactate dehydrogenase - pyruvate can be turned into glucose during gluconeogenesis

Question 32

In order for lactate not to damage skeletal muscle when levels are high it must be removed. This is done by the MCT-1 transporter. Lactate then enters the blood. Alongside lactate, what else is pumped into the blood? 1 - Na+ 2 - K+ 3 - H+ 4 - Cl-

Answer 32

3 - H+ - produced during the hydrolysis of lactate - high levels of lactate and H+ dumped into the blood can cause metabolic acidosis

Question 33

Lactate produced by skeletal muscle is released into the blood via the MCT-1 transporters. It is then taken up by what organ? 1 - spleen 2 - lungs 3 - liver 4 - heart

Answer 33

3 - liver

Question 34

Once lactate is back in the liver, what happens to it? 1 - converted into glucose by lactate dehydrogenase 2 - converted into pyruvate by lactate dehydrogenase 3 - converted into ATP by lactate dehydrogenase 4 - converted into glycogen by lactate dehydrogenase

Answer 34

2 - converted into pyruvate by lactate dehydrogenase - 2 pyruvate can then be converted into glucose via gluconeogenesis

Question 35

During normal physiological conditions the bodies normal metabolism creates how much lactic acid per day? 1 - 2 mmol/kg/day lactic acid 2 - 20mmol/kg/day lactic acid 3 - 200 mmol/kg/day lactic acid 4 - 2000 mmol/kg/day lactic acid

Answer 35

2 - 20mmol/kg/day lactic acid

Question 36

The liver and spleen are able to clear lactic acid from the body to reduce the risk of metabolic acidosis. What are the normal levels of clearance of lactic acid possible by the liver and kidneys? 1 - 8 to 18 mL/min 2 - 80 to 180 mL/min 3 - 800 to 1800 mL/min 4 - 8000 to 18000 mL/min

Answer 36

3 - 800 to 1800 mL/min

Question 37

Which of the following is not a cause of hyperlactataemia (raised lactate)? 1 - extreme exercise 2 - sepsis 3 - critical illness 4 - cardiogenic shock 5 - respiratory failure type 1 6 - liver failure 7 - open heart surgery

Answer 37

5 - respiratory failure type 1

Question 38

What are normal circulating lactate levels? 1 - 0.2 mmol/L 2 - 2 mmol/L 3 - 8 mmol/L 4 - >15 mmol/L

Answer 38

2 - 2 mmol/L

Question 39

What is a common circulating lactate level in a critically ill patient? 1 - 0.2 mmol/L 2 - 2 mmol/L 3 - 8 mmol/L 4 - >15 mmol/L

Answer 39

4 - >15 mmol/L

Question 40

Is a relative increase of 0.75 mmol/L associated with increased mortality?

Answer 40

- yes

Question 41

Glycolysis and proteolysis are both increased during sepsis. What effect does this have on lactate levels?

Answer 41

- increased lactate

Question 42

What is multi organ dysfunction syndrome? 1 - dysfunction of 1 organ 2 - dysfunction of 2 organs 3 - dysfunction of 2 or more organs 4 - dysfunction of all organs

Answer 42

3 - dysfunction of 2 or more organs - the level of dysfunction cannot be maintained without some form of intervention

Question 43

Which 2 organs often provide the first evidence that a patient is entering multiple organ dysfunction syndrome? 1 - liver and heart 2 - heart and lungs 3 - lungs and liver 4 - liver and kidney

Answer 43

2 - heart and lungs - presents as acute lung injury/acute respiratory distress syndrome

Question 44

Once the lungs and heart start presenting with signs of multiple organ disfunction syndrome, which presents as lung injury/acute respiratory distress syndrome, what are the next 2 organs to be affected? 1 - liver and heart 2 - heart and lungs 3 - lungs and liver 4 - liver and kidney

Answer 44

4 - liver and kidney

Question 45

In multiple organ disfunction syndrome, what are often the last 2 systems that are affected? 1 - bone marrow and myocardial 2 - heart and lungs 3 - lungs and liver 4 - liver and kidney

Answer 45

1 - bone marrow and myocardial