Switching on a fuel supply Flashcards
What are the actions of insulin?
- Increased glucose uptake in muscle, fat and liver
- Decreased lipolysis
- Decreased AA release from muscle
- Decreased gluconeogenesis in liver
- Decreased ketogenesis in liver
Why is it good to establish breastfeeding quickly?
- little milk available at first
- newborn has to meet demands from stores
- Requirement = 4-6g glucose /kg/day
- Later milk is available as a high fat food - 50% of calories in it is fats
How are stores converted to fuels?
- Anabolic actions of insulin are opposed by counter-regulatory (catabolic) hormones: glucagon, adrenaline, cortisol, GH
What is the glucagon surge?
- As plasma glucose levels fall at birth, plasma glucagon levels rise rapidly
- This activates gluconeogenesis, opposing insulin
What happens during a postnatal fast?
- The baby will need to utilise stores to provide glucose as an energy source for the tissues
- Gluconeogenesis is the process of providing glucose from stores - muscle (AAs and glycogen) and fat via substrates such as lactate, pyruvate, alanine and glycerol
- Ketogenesis is the process of providing ketone bodies (which ac as a fuel) from the breakdown of fat
What are the 3 rate limiting steps in the gluconeogenesis process?
- PEPCK, F1,6-BPase and G6pase
How is fat oxidised?
- Terminal two carbon group is removed from FA and bound to coenzyme A, as acetyl CoA (beta oxidation)
- Acetyl groups can then be utilised to form ketone bodies (acetone and beta-hydroxybutyrate)
- Acetyl groups can also enter the Kreb’s cycle as an energy source
What is the fasting (post-absorptive) state?
- Straight after eating
- Substrates are mobilised peripherally through action of counter-regulatory hormones (catecholamines, cortisol and glucagon)
- Insulin is opposed
What sort of problems can babies have with metabolism?
- Demand exceeds supply
- Hyperinsulinism
- Counter-regulatory hormone deficiency
- IEM
What problems will an extremely small preterm baby have?
- High demands, small nutrient stores
- Immature intermediary metabolism
- Establishment of enteral feeding delayed
- Poor fat absorption - GIT wont work well, can put milk in, but wont be absorbed properly
- Extremely little fat stores to maintain blood glucose levels - they will go down and stay down
What problems will an IUGR (inuterine growth restriction) baby have?
- High demands (especially brain)
- Low stores (liver, muscle, fat)
- Immature gluconeogenic pathways
What problems may arise if the mother is diabetic?
- High maternal glucose and so high foetal glucose
- Foetal and neonatal hyperinsulinism
- Neonatal macrosomia and hypoglycaemia
- At risk of very problemati hypoglycaemia - wont have made ketones so one of the defence mechanisms has gone
What are other causes of hyperinsulinism?
- Beckwith Wiedemann
- Islet cell dysregulation - Nesiodioblastosis
What are symptoms of Beckwith Wiedemann?
- Macroglossia
- macrosomia (big baby)
- Midline abdominal wall defects (exomphalos, umbilical hernia, diastasis recti)
- Ear creases or ear pits
- Hypoglycaemia
What causes CAH?
21 hydroxylase deficiency
- Build up of androgens - cannot make aldosterone or cortisol
What IEMs can cause neonatal hyPOglycaemia?
- Glycogen storage disease (usually type 1)
- Galactosaemia
- Medium chain acyl-CoA dehydrogenase deficiency (MCAD)
What is glycogen storage disease (type 1)?
- Deficiency of G-6-phosphatase
- Hypoglycaemia and lactic acidosis in newborn
- hepatomegaly in older child
What causes galactosaemia?
- lactose in milk is broken down to galactose and glucose
- Galactose is then broken down to glucose by galactose-1-phosphate uridyl transferase
- This enzyme is missing in galactosaemia, leading to toxic levels of galactos-1-phosphate
What are the symptoms of galactosaemia?
- Hypoglycaemia
- Jaundice and liver disease
- Poor feeding and vomiting
- Cataracts and brain damage
- E coli sepsis
SUMMARY
- insulin dominates in the foetal state
- Counter-regulatory hormones (esp glucagon) have vital role in postnatal metabolic adaptation
- Tissue stores, particularly fat laid down in 3rd trimester are important energy stores in the first few days
- metabolic adaptation to extrauterine life is compromised by IUGR, preterm birth or IEM
