Metabolic response to sepsis, injury and starvation Flashcards
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
1 - glycogenolysis and gluconeogenesis increases
glycogenolysis = glycogen breakdown
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
4 - ketones are produced from stored fat and glycogen stored are depleted
- fat becomes the main energy source
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
4 - liver generates ketones from fat stores
- glucose is not essentially here as ketones are used from fat
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
2 - β-hydroxy butyrate, acetone and acetoacetate
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
3 - ketones cause metabolic acidosis and HCO3- butters
- normal HCO3- = 22-26mmol/L
- milk ketosis HCO3- = 7-8 mmol/L
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
3 - ~ 1mmol/L
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
2 - ~ 8-10mmol/L
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
3 - proteolysis produces gluconeogenic amino acids
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%
3 - 50%
During phase 3 of starvation, catabolic weight loss, what happens to the bodies wound healing, immune response, GI integrity, mobility, mental state and energy?
- all decrease
Is ketosis always a bad thing?
- no
- good for T2DM, weight loss and epilepsy as examples
What happens to the glucose, insulin and glucagon during ketosis?
- low glucose
- low insulin
- high glucagon
What affect do ketones have on lipolysis?
- ketones inhibit lipolysis
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
4 - epinephrine and cortisol
Starvation can cause a decrease in metabolic rate. Does the metabolic rate during an injury increase or decrease?
- increase
- body needs energy to repair itself
What happens to blood glucose utilisation and blood glucose levels during injury?
- both increase
- tissues need energy to repair
Starvation can cause an increase in gluconeogenesis. What happens to gluconeogenesis during injury?
- increased
- body tries to get as much energy as possible for repair
During starvation protein catabolism and urinary nitrogen (breakdown product of amino acid oxidation) are low, but what happens during injury?
- catabolism is increased
- urinary nitrogen is increased
During starvation fat catabolism and ketone utilisation are high as the body tries to make energy. But what happens during injury?
- fat catabolism and ketone utilisation are low
In starvation weight loss is slow, is there any weight loss during injury?
- rapid weight loss
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
2 - exaggerated immune response causing systemic inflammation
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
3 - 2 or more
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
- -
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
1st = - major burns
2nd = multi trauma and skeletal trauma
3rd = closed head injury
4th = sepsis
5th = elective surgery
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%
4 - 70%
- under feeding increases mortality rates
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
2 - decreased insulin sensitivity
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
4 - decreased insulin sensitivity and glucose uptake
- basically causes insulin resistance
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?
- reduce bodies ability to use fat as energy
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)
2 - proteolysis from skeletal muscle
- ability to increase glycolysis and lactate production is associated with improved survival
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+
2 - lactate
- pyruvate is converted into lactate by lactate dehydrogenase
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?
- no
- converting pyruvate to lactate creates NAD+ which can be used in glycolysis
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-
3 - H+
- produced during the hydrolysis of lactate
- high levels of lactate and H+ dumped into the blood can cause metabolic acidosis
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
3 - liver
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
2 - converted into pyruvate by lactate dehydrogenase
- 2 pyruvate can then be converted into glucose via gluconeogenesis
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
2 - 20mmol/kg/day lactic acid
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
3 - 800 to 1800 mL/min
Which of the following is not a cause of hyperlactataemia?
1 - extreme exercise
2 - sepsis
3 - critical illness
4 - cardiogenic shock
5 - respiratory failure type 1
6 - liver failure
7 - open heart surgery
5 - respiratory failure type 1
What are normal circulating lactate levels?
1 - 0.2 mmol/L
2 - 2 mmol/L
3 - 8 mmol/L
4 - >15 mmol/L
2 - 2 mmol/L
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
4 - >15 mmol/L
Is a relative increase of 0.75 mmol/L associated with increased mortality?
- yes
Glycolysis and proteolysis are both increased during sepsis. What effect does this have on lactate levels?
- increased lactate
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
3 - dysfunction of 2 or more organs
- the level of dysfunction cannot be maintained without some form of intervention
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
2 - heart and lungs
- presents as acute lung injury/acute respiratory distress syndrome
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
4 - liver and kidney
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
1 - bone marrow and myocardial
