Early Life Programming Flashcards
What is programming?
An insult/stimulus that occurs at a critical period in development and which has lasting or lifelong consequences
What is the thrifty phenotypes hypothesis?
Foetus and early infant become metabolically thrifty in adverse nutritional circumstances. This thrift results in impaired glucose metabolism.
Impaired beta cell growth in pancreas means that in later life, pressure on pancreas causes intolerance (diabetes)
How much of birth weight is influenced by the environment?
62%
Why might human offspring be vulnerable to a thrifty phenotype?
- low protein intake
- low carbohydrate intake
- low micronutrient intake
- iron deficiency and anaemia (impacts growth of foetus)
Overall, any nutritional stress (I.e.famine) means poor nutrition and poor growth
Describe the foetal circulation
- umbilical vein transports maternal blood from placenta to foetus via umbilicus
- umbilical vein splits into portal sinus (supplies liver) and ductus venous where maternal blood joins inferior vena cava
- inferior vena cava enters heart and bypasses the right ventricle by instead entering directly into the left atrium via the foremen ovale
- blood gets pumped by left ventricle into the aorta and to the rest of the body
- as inferior vena cava and superior vena cava drain into the right atrium, oxygenated and deoxygenated blood becomes mixed. Aside from the foramen ovale, blood also gets pumped by the right ventricle into the pulmonary trunk. However, there is a shunt called the ductus arteriosus which allows the blood in the pulmonary trunk to bypass the pulmonary circulation and join the aortic circulation from the left ventricle. This is needed as the lungs are filled with amniotic fluid and cannot work
How does the foetus react to decreased maternal nutrition?
It will ultimately prioritise the heart and brain. Therefore, depending on how bad the nutrition is the foetal circulation will vasoconstrict to prioritise regions that need blood the most e.g. more blood flow through ductus venosas rather than portal sinus = less liver growth
If nutrition is very bad this is called the brain-sparing effect
What is the outcome of the brain-sparing effect in the foetus?
- low pancreas
- low kidney weight and nephron number
- increased resistance to blood flow in superior mesenteric artery
- IUGR
- fatty liver
- small abdo organs
What is IUGR associated with later in life?
- Diabetes
- Ischaemic heart disease
- syndrome X (micro vascular angina)
What is low size of pancreas and beta cells associated with later in life?
Small pancreas and beta cells dysfunction (diabetes)
What is altered hepatic flow associated with later in life?
- Altered hepatic metabolism
- increased glucose output and PEPCK
What does impaired postnatal ketogenesis link to later in life?
Impaired ketogenesis
What is thin, decreased adipose tissue associated with later in life?
Obesity
What is low renal flow associated with later in life?
Hypertension
What is fatty liver IUGR and malnutrition associated with later in life?
Fatty liver and type 2 diabetes
What is the outcome of maternal obesity (overnutrition) for the foetus?
- childhood obesity
- childhood cancer
- hypertension
- diabetes
- morbidity
- adult obesity
