Parental Nutrition

Question 1

When is PN appropriate and why dont we give it to everyone?

Answer 1

• PN used when a patient is unable to tolerate EN for a significant period of time
• not given as a first resort due to risks with infection, expense, gut is bypassed which compromises immune and barrier functions, metabolic signalling of the gut is not used, metabolic consequences of PN

Question 2

Consequences of using glucose in PN metabolism

Answer 2

• goes straight into the superior vena cava and in the circulation, and so bypasses the gut (which would normally consume 10% of glucose in adults and 33% in infants)
• however leads to insulin spike which promotes adipose tissue deposition and hepatic steatosis (which also increases EE)
• also increases CO2 production so may need for intense ventilation
• there is also an increased risk of hyperglycaemia which increases risk of death and complications

Question 3

Use of lipids in PN

Answer 3

• patients who receive no essential fatty acids run into dermatological problems
• lipids are delivered in PN directly into the superior vena cava and into the circulation, not much lipid would have been lost if given EN as liver bypassed (through lymphatic system) and the intestine do not use much lipid
• as TAG particles in PN circulate they acquire characteristics of chylomicrons i.e they acquire apo proteins and cholesterol. Can be hydrolysed by lipoprotein lipase and NEFA can be used as energy source by periphery, either by direct oxidation or production of ketone bodies HOWEVER metabolic stress can inhibit LPL and lead to very high TAG which can lead to pancreatitis
• if lipids are not cleared during feeding this can lead to lipid peroxidation (a marker of this is malondialdehyde) therefore vitamin E is given concurrently. However giving excess glucose also leads to an increase in peroxidation
• can lead to PNAC (parental nutrition associated cholestasis- impaired liver function and could lead to a liver transplant) which may be due to phytosterols, which in high levels can cause increased hepatic lipogenesis and bile acid synthesis
• another reason for PNAC may be too high omega 6: omega 3 ratio from soybean oil, therefore recommended to use fish oil rather than soybean (fish oil can decrease bilirubin levels, a sign of PNAC)

Question 4

Antioxidant defences (CuZn SOD, MnSOD, catalase, glutathione peroxidase, micronutrients given in PN to maximise antioxidant activity)

Answer 4

• CuZnSOD: lung extracellular fluids and plasma can convert superoxide to H2O2
• MnSOD: intracellular (mitochondrial) converts superoxide to H2O2
• catalase: contains Fe3+ at the active site in peroxisomes converts H2O2 to H2O and O2
• glutathione peroxidase: can work extracellularly or in the mitochondria to convert H2O2 to H2O or handling lipid peroxides using glutathione. Glutathione reductase then regenerates glutathione using NADPH (generated by PPP). Contains selenocysteine in the active site, and adequate selenium intake is needed for maximal activity
• micronutrients given in PN to support antioxidant activity: iron, copper, zinc, manganese, selenium

Question 5

Use of amino acids in PN (glutamine, SIGN trial)

Answer 5

• protein requirements change during acute illness (i.e higher rates of acute phase reactant proteins)
• tyrosine needs to be supplemented in infants as although conditionally essential, demands are very high
• AA through intestine can lead to a lot of losses (especially glutamine) therefore PN requirements can be lower
• glutamine conditionally essential in illness (as key N donor between tissues) and fuel source for cells of immune system and enterocytes, and as a precursor for glutathione (for GSHPx)
• SIGN trial however showed that greater supplementation of glutamine caused weight loss, and decrease in head circumference in infants. This may have been because intake of other amino acids was sub-optimal