MEH: Metabolic & Endocrine Control During Special Circumstances

Question 1

What are the major metabolic fuels and their sources in the normal individual

Answer 1

Normally available in the blood:

• glucose (preferred fuel source)
• fatty acids

Question 2

Fatty acids are an example of a metabolic fuel normally available in the blood. Which cells can use

Answer 2

Can be used as fuel by most cells except red blood cells, brain and CNS

Question 3

Which fuel sources are available under special conditions

Answer 3

Amino acids: converted to glucose or ketone bodies
Ketone bodies: mainly from fatty acids, used when glucose is critically short
Lactate: liver can convert back to glucose via the Cori Cycle or can be utilised as fuel source for TCA cycle in other tissues

Question 4

What are the main energy stores

Answer 4

Glycogen (about 400g stored in liver and muscle)
Fat (TAG in adipose tissue, about 10-15 kg)
Muscle protein (about 6 kg, used in emergency)

Question 5

Describe the process of feeding to starvation

Answer 5

1) feeding
2) glucose available from the gut for up to 2 hours. Immediate metabolism supported by glucose, making glycogen as quickly as possible and increasing fat stores.
3) from 2-10 hours, glucose and fats are no longer being absorbed. Blood glucose maintained by glycogen and fatty acids support other metabolic activity
4) no food for 8-10 hours, glycogen stores are depleted. Need to make more glucose for the brain via gluconeogenesis
5) starvation: fatty acid metabolism produces ketone bodies and brain becomes able to metabolise ketone bodies

Question 6

What are the 2 anabolic hormones

Answer 6

Promotes fuel and storage

• insulin
• growth hormone

Question 7

Give 2 catabolic hormones

Answer 7

Promotes release from stores and utilisation

• glucagon
• adrenaline
• cortisol
• GH
• thyroid hormones

Question 8

Insulin. What processes are inhibited (5) and what processes are stimulated. (4)?

Answer 8

Inhibited: gluconeogenesis, glycogenolysis, lipolysis, ketogenesis, proteolysis
Stimulated: glucose uptake in muscle and adipose via GLUT 4, glycolysis, glycogen synthesis, protein synthesis

Question 9

Effects of feeding (4)

Answer 9

Increase in blood glucose
Pancreatic beta cells release insulin
Promote glucose uptake (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 storage of fatty acids as TAG in adipose tissue

Question 10

Effects of fasting (5)

Answer 10

Blood glucose falls and insulin secretion depressed
Reduces uptake of glucose by adipose and muscle
Glucagon released which stimulates: glycogenolysis in liver, lipolysis in adipose tissue & gluconeogenesis

Question 11

Effects of energy starvation (6)

Answer 11

Reduction of blood glucose stimulates release of cortisol in adrenal glands and glucagon from pancreas
Stimulates gluconeogenesis and breakdown of protein and fat
Reduction in insulin and anti-insulin effects of cortisol prevent most cells from using glucose and fatty acids are preferentially metabolised
Ketone bodies produced by liver
Kidneys contribute to gluconeogenesis,
Deplete fat stores, protein used as fuel

Question 12

Complications of refereeing syndrome

Answer 12

Urea cycle has been down regulated so if you give lots of protein, ammonia toxicity will occur

Hypophosphataemia (rapid kickstart of metabolic pathways… needs phosphate… low phosphate already due to starvation)

Question 13

When does 2/3rds of fetal growth occur

Answer 13

Last trimester

Question 14

Mother’s net weight gain by end of pregnancy

Answer 14

8kg

Question 15

Out of the 8kg weight gain, how much is maternal fuel stores and how much is foetus

Answer 15

Maternal fuel stores: 3kg

Foetus: 3.5 kg

Question 16

Two main phases of pregnancy

Answer 16

1) anabolic phase: increase in maternal fat stores, increase in insulin sensitivity, nutrients stored
2) catabolic phase: decreased insulin sensitivity (maternal insulin levels continue to increase but the production of anti insulin hormones by fetal placental unit increases at an even faster rate and the insulin/anti-insulin ratio therefore falls), increase in maternal glucose and free fatty acid concentration therefore allows for greater substrate availability for foetus. Transient hyperglycaemia after meals due to anti insulin hormones (corticotropin releasing hormones), reducing maternal utilisation of glucose by switching tissues to use of fatty acids

Question 17

Placental transfer

Answer 17

Most substances transfer by simple diffusion down concentration gradient
Glucose in principal fuel for fetus and transfer facilitated by transporters (GLUT1)

Question 18

The placenta, fetal adrenal glands and fetal liver constitute a new endocrine entity known as

Answer 18

Fetoplacental unit

Question 19

Placenta secretes a wide range of proteins that can control the maternal hypothalamic pituitary axis

Answer 19

HYPOTHALAMIC LIKE RELEASING HORMONES:
CRH, GnRH, TRH, GHRH

Pituitary like hormones: ACTH, hCG, cCT, hPL

Important placental steroid hormones include:
Progesterone and oestriol

Question 20

What are the anti insulin hormones produced in placenta

Answer 20

Corticotropin releasing hormone resulting in increased in ACTH and cortisol
Results in transient hyperglycaemia after meals because of increased insulin resistance

Also, human placental lactose and progesterone

Question 21

How does gestational diabetes occur

Answer 21

Oestrogens and progesterone increase sensitivity of maternal pancreatic beta cells to blood glucose therefore increased insulin synthesis and secretion

If beta cells do not respond normally, blood glucose elevates and it occurs

Question 22

gestational diabetes: pancreatic beta cells do not produce sufficient insulin to meet increased requirement in late pregnancy.

Give 3 known underlying causes and 3 complications

Answer 22

Autoantibodies similar to those of Type 1 DM, genetic susceptibility, in setting of obesity and chronic insulin resistance

Increased risk of miscarriage, congenital malformation, fetal macrosomia (—> shoulder dystocia), gestational hypertension, pre-eclampsia

Question 23

Risk factors of gestational diabetes

Answer 23

Family history of gestational diabetes
Family history of macrosomia
Race/ethnicity: more common in Asian, black and Hispanic ethnic groups
Maternal age of older than 25
BMI higher than 25

Question 24

How to manage gestational diabetes

Answer 24

Diet modification, maybe caloric reduction in obese patients
Insulin injections if persistent hyperglycaemia
Regular ultrasounds to check fetal growth and wellbeing

Question 25

How to replenish ATP stores after the 2 seconds usage

Answer 25

1) Muscle creatine phosphate (only 5 seconds worth ish)

2) Glycolysis and OP (need to draw in energy stores to provide substrate for these pathways)

Question 26

What is Cori cycle

Answer 26

Muscles under anaerobic conditions convert glucose to 2 lactate.
Travels in blood to liver
2 Lactate converted to glucose here
Travels back to muscle

Repeat

Question 27

How does exercise help glucose uptake

Answer 27

Insulin independent process of glucose uptake

AND

muscle takes up blood glucose via GLUT4 and GLUT1

Question 28

What happens in 100m sprint. (Where you cannot deliver sufficient oxygen to muscles)

Answer 28

Immediate 5 seconds: creatine phosphate used

After, produces lactate and build up in H+

Question 29

What happens in 1500 middle distance where some oxygen can get to muscles

Answer 29

1) uses creatine phosphate and anaerobic glycogen metabolism
2) ATP produced aerobically from muscle glycogen
3) finishing sprint relies on anaerobic metabolism of glycogen and produces lactate

Question 30

In marathon, what happens (95% aerobic)

Answer 30

Use of muscle glycogen, liver glycogen and fatty acids for aerobic metabolism

Question 31

Hormonal control of metabolic response to prolonged exercise

Answer 31

Insulin levels fall
Glucagon levels rise (glycogenolysis, gluconeogenesis, lipolysis)
Adrenaline and GH increase (glycogenolysis, gluconeogenesis, lipolysis)
Cortisol rises (lipolysis, gluconeogenesis)