20. Metabolic And Endocrine Control During Special Cirumstances Flashcards
What are the fuel sources normally available in the blood?
Glucose
Fatty acids - except RBC, brain and CNS
What fuel sources are available under special conditions?
Amino acids
Ketone bodies
Lactate
What are the anabolic hormones in metabolic control and what do they do?
Insulin
Growth hormone - increased protein synthesis
Promote fuel storage
What are the catabolic hormones in metabolic control and what do they do?
Glucagon Adrenaline Cortisol Growth hormone - increases lipolysis and gluconeogenesis Thyroid hormones
Promote release from stores and utilisation
What does insulin prevent?
Gluconeogenesis Glycogenolysis Lipolysis Ketogenesis Proteolysis
What does insulin promote?
Glucose uptake in muscle and adipose (GLUT4)
Glycolysis
Glycogen synthesis
Protein synthesis
What are the effects of feeding?
Increase in blood glucose stimulates pancreas to release insulin
Increase glucose uptake and utilisation by muscle and adipose (GLUT4)
Promotes storage of glucose as glycogen in liver and muscle
Promotes amino acid uptake and protein synthesis in liver and muscle
Promotes lipogenesis and stage of fatty acids as triacylglycerol in adipose tissue
What are the effects of fasting?
Blood glucose falls and insulin secretion depressed
Reduces uptake of glucose by adipose and muscle
Low blood glucose stimulates glucagon which stimulates:
- glycogenolysis in liver
- lipolysis in adipose tissue
- gluconeogenesis to maintain supplies of glucose for brain
What does the reduction of blood glucose stimulate the release of?
Cortisol from adrenal cortex
Glucagon from pancreas
What processes does energy starvation stimulate?
Gluconeogenesis and breakdown of protein and fat
What does the reduction in insulin and anti-insulin effects of cortisol do?
Prevent most cells from using glucose and fatty acids are preferentially metabolised
What does the liver start to produce in energy starvation?
Keaton bodies and brain starts to utilise these sparing glucose requirement from protein
What are the 2 main bases of metabolic adaptation during pregnancy?
Anabolic phase
Catabolic phase
What happens in the anabolic state in pregnancy?
In early pregnancy
Increase in maternal fat stores
Small increase in level of insulin sensitivity
Nutrients are stored to meet future demands of rapid fetal growth in late gestation and lactation after birth
What happens in the catabolic state in pregnancy?
Late pregnancy
Decreased insulin sensitivity
Increase in insulin resistance results in an increase in maternal glucose and free fatty acid concentration
Allows for greater substrate availability for fetal growth
How are substances transferred across the placenta?
Not substances transfer by simple diffusion down concentration gradients
Glucose is principal fuel for fetus and transfer facilitated by transporters (GLUT1)
What is the fetoplacental unit?
The placenta, fetal adrenal glands and fetal liver constitute a new endocrine entity
What does the placenta secrete?
Wide range of proteins that can control the maternal hypothalamic pituitary axis
What are the hypothalamic like releasing hormones?
Corticotropin releasing hormone (CRH)
Gonadotropin releasing hormone (GnRH)
Thyrotropin releasing hormone (TRH)
Growth hormone releasing hormone (GHRH)
What are the pituitary like hormones?
ACTH
Human chorionic gonadotropin (hCG)
Human chorionic thyrotropin (cCT)
Human placental lactose needs (hPL)
What are the important steroid hormones released?
Oestriol
Progesterone
Why does the maternal metabolism change during the first 20 weeks of pregnancy?
Related to a preparatory increase in maternal nutrient stores (mainly adipose tissue)
In preparation for rapid growth rate of fetus, birth, subsequent lactation
What are the maternal metabolic changed during the second half of pregnancy?
Concentration of nutrients in the maternal circulation kept relatively high by:
- reducing maternal utilisation of glucose by switching tissues to use of fatty acids
- delaying maternal disposal of nutrients after meals
- releasing fatty acids from stores built up during 1st half of pregnancy
What happens to the maternal insulin in the second half of pregnancy?
Levels continue to increase but the production of anti-insulin hormones by the fetal-placental unit increases at an even faster rate and the insulin/anti-insulin ratio therefore falls
What are the anti-insulin hormones?
Corticotropin releasing hormone
Human placental lactogen
Progesterone
How does corticotropin releasing hormone work?
Maternal anterior pituitary becomes desensitised resulting in s more modest increase in ACTH and cortisol
What do oestrogens and progesterone do in terms of insulin secretion in pregnancy?
Increase sensitivity of maternal pancreatic beta-cells to blood glucose
Beta-cell hyperplasia
Beta-cell hypertrophy
Leads to increased insulin synthesis and secretion
What happens if beta cells do not respond normally in pregnancy?
Blood glucose may become seriously elevated and gestational diabetes may develop
What is gestational diabetes?
Disease in which pancreatic beta cells do not produce sufficient insulin to meet increased requirement in later pregnancy
What are the 3 known underlying causes of gestational diabetes?
Autoantibodies similar to those characteristic of type 1 DM
Genetic susceptibility similar to maturity onset diabetes
Beta cell dysfunction in setting of obesity and chronic insulin resistance
What are the clinical implications of gestational diabetes?
Increased incidence of miscarriage
Incidence of congenital malformation 4x higher
Fetal macrosomia - leading to shoulder dystocia
Associated hypertensive disorders of pregnancy such as gestational hypertension and preeclampsia
What are the risk factors of gestational diabetes?
Maternal age >25 years BMI >25kg/m^2 Race/ethnicity - more common in Asian, black and Hispanic ethnic groups Personal or family history of diabetes Family history of macrosomia
What is the management of gestational diabetes?
Initial dietary modification including calorific reduction in obese patients
Insulin injection if persistent hyperglycaemia is present
Regular ultrasound scans to assess fetal growth and well being
Where does energy come from for exercise?
Muscle creatine phosphate stores can rapidly replenish ATP to provide immediate energy
Still only enough for 5 seconds worth of energy during a 100m sprint
Beyond initial burst of energy, further ATP supplied by glycolysis and oxidative phosphorylation
What can additional intensive exercise (anaerobic) for up to 2 mins be supplied by?
Breakdown of muscle glycogen
What is the cori cycle?
Glucose used up in muscles, produces lactate
Lactate transported to liver via blood
Liver recycles lactate into glucose
Glucose transported back to muscles via blood
How does muscle take up blood glucose?
Via GLUT4 transporter and GLUT1
When can fatty acids be used as fuel?
In aerobic conditions
- slow release from adipose tissue
- limited crying capacity in blood
- capacity limited by uptake across mitochondrial membrane (carnitine shuttle)
What is the hormonal control of the metabolic response to prolonged exercise?
Insulin levels fall slowly
Glucagon levels rise - stimulates glycogenolysis, gluconeogenesis and lipolysis
Adrenaline and growth hormone rise rapidly
Cortisol rises slowly - stimulates lipolysis of gluconeogenesis
What are the benefits of exercise?
Body composition changes Glucose tolerance improves Insulin sensitivity of tissues increases Blood triglycerides decrease Blood pressure falls Psychological effects
