Switching On And Maintaining A Fuel Supply Flashcards
How much glucose does the fetus near term use?
~ 5 g glucose / kg / day - substrated are principally glucose + amino acids
What is the dominant hormone and its role in the fetus near term?
Insulin - works as an anabolic hormone -> removes glucose from circulation into the fat stores, acts as a growth hormone - ‘baby building hormone’.
Beta cells in pancreas undergo hyperplasia in 3rd trimester -> insulin secreted.
What are the actions of insulin?
- Increase glucose uptake in muscle, fat + liver
- Decrease lipolysis
- Decrease amino acid release from muscle
- Decrease gluconeogenesis in liver
- Decrease ketogenesis in liver
What is the energy requirement for a newborn?
~ 4-6 g glucose /kg/day
How does the newborn meet its energy demands?
- Little milk available at first - baby gets colostrum + 7mls/feed in first 24 hours
- Newborn initially has to meet demand from stores (metabolism)
- Later, milk is available as a high fat food
- Newborn must manage demand as well as supply
In terms of demand, how is energy partitioned in newborns?
- In babies the brain accounts for a higher proportion of resting energy expenditure
- But the cerebral metabolic rate (CMRglucose) is relatively low at birth
In terms of supply and energy stores, describe the weight of the baby
- ~1% glycogen (stored in liver)
- ~16% fat
How are stores converted to fuels?
The anabolic actions of insulin are opposed by the counter-regulatory (catabolic) hormones.
Name some counter-regulatory (catabolic) hormones that oppose anabolic actions of insulin
- Glucagon
- Adrenaline
- (Cortisol)
- (Growth hormone)
Describe what happens during a glucagon surge
As plasma glucose levels fall at birth, plasma glucagon levels rise rapidly -> activates gluconeogenesis, opposing insulin.
How does the baby utilise stores to provide glucose as an energy source for the tissues (during a postnatal fast)?
- Gluconeogenesis - process of providing glucose from stores - muscle (amino acids + glycogen) and fat via substrates such as lactate, pyruvate, alanine + glycerol.
- Ketogenesis - process of providing ketone bodies (act as fuel) from breakdown of fat. Ketones tend to be higher in the newborn period in comparison to adults.
What are 3 rate-limiting steps within gluconeogenesis?
- G-6-P ase
- F1,6 BP ase
- PEPCK
Describe the structure of fats
- Glycerol backbone (3 carbon skeleton)
- Fatty acids attach (saturated or unsaturated)
Describe the oxidation of fat and in turn formation of ketone bodies
- Terminal two carbon group removed from fatty acid and bound to coenzyme A, as acetyl CoA (beta-oxidation)
- Acetyl groups can then be utilised to form ketone bodies (acetone + beta-hydroxybutyrate)
- OR Acetyl groups can also then enter the Kreb’s cycle as an energy source
What happens in the fasting (post-absorptive) state?
- Substrates are mobilised peripherally through action of counter-regulatory hormones (catecholamines, cortisol, glucagon)
- Insulin is opposed
What happens in the fed (post-prandial) state?
- Infant diet (milk) is 50% fat and 40% carbohydrate
- CHO is mainly lactose
- Breast milk contains a lipase
- Insulin acts to store blood glucose in tissues
- In liver, excess glucose made into glycogen
What general kind of problems can babies have?
- Demand exceeds supply
- Hyperinsulinism
- Counter-regulatory hormone deficiency
- Inborn errors of metabolism
What happens to a baby when the demand exceeds the supply?
- Extremely small preterm baby
- High demands
- Small nutrient stores
- Immature intermediary metabolism
- Establishment of enteral feeding delayed
- Poor fat absorption
What is the difference between being ‘small for gestational age’ and ‘intrauterine growth restriction’?
- Small for gestational age - form lower percentile level but can be normal
- Intrauterine growth restriction indicates pathological process that causes growth restriction
Describe the infant of the diabetic mother
- High maternal glucose -> high fetal glucose
- Fetal and neonatal hyperinsulinism (producing more insulin)
- Insulin acts as a growth hormone
- -> Neonatal macrosomia + hypoglycaemia
Not all babies will be macrosomic so could look fine but have a problem of hypoglycaemia.
Another cause of hyperinsulinism in the baby is Beckwith Wiedemann syndrome - what features will the baby have?
- Macroglossia (large tongue)
- Macrosomia
- Midline abdominal wall defects (exomphalos, umbilical hernia, diastasis recti)
- Ear creases or ear pits
- Hypoglycaemia
What is another cause of hyperinsulinism (that isn’t a diabetic mother or Beckwith Wiedemann Syndrome)?
Islet cell dysregulation: Nesiodioblastosis
How does congenital adrenal hyperplasia cause virilisation, salt-wasting and hypoglycaemia?
- Congenital adrenal hyperplasia -> virilsation in the womb -> enzyme defect (21 OH deficiency) -> don’t produce cortisol or aldosterone
- -> pre-cursors build up to cause virilisation (testosterone prod inc).
- -> less cortisol (counter-reg hormone) -> hypoglycaemia
- -> lack of aldosterone -> salt-wasting crisis
What are other deficiencies of counterregulatory hormones apart from CAH/cortisol?
- Hypothalamic-pituitary-adrenal insufficiency: septo-optic dysplasia
- Waterhouse-Friderichsen syndrome: severe adrenal haemorrhage with adrenal gland dysfunction secondary to sepsis or hypoxia
What are causes of neonatal hypoglycaemia? AKA inborn errors of metabolism
- Glycogen storage disease (type 1)
- Galactosaemia
- MCAD (medium chain acyl-CoA dehydrogenase deficiency)
What is glycogen storage disease (type 1)?
- Deficiency of glucose-6-phosphatase
- Hypoglycaemia and lactic acidosis in newborn
- Hepatomegaly in older child
What is galactosaemia?
- Lactose in milk is broken down to galactose + glucose
- Galactose is then broken down to glucose by galactose-1-phosphate Uridyl Transferease (Gal-I-put) which is missing in Galactosaemia, leading to toxic levels of galactose-1-phosphate
- Presents with:
- > hypoglycaemia
- > jaundice + liver disease
- > poor feeding + vomiting
- > cataracts + brain damage
- > E coli sepsis
