L18: Metabolic and Endocrine control during special circumstances Flashcards

Question

What effect does fasting have on metabolism?

Answer 1

Low blood glucose—> Increase glucagon secretion and inhibit insulin secretion —> Increase glycogenolysis—> increase glucose for brain and other dependent tissues —> Lipolysis—> provide fatty acids for other tissues —> Gluconeogenesis—> maintain supplies of glucose to the brain

Answer 2

Inadequate intake of energy in a previously well nourished individual

Answer 3

1. Initially blood glucose maintained by glucagon—> breakdown of hepatic glycogen 2. Reduced blood glucose—> Pituitary releases ACTH—> cortisol increases 3. Simulates gluconeogenesis and breakdown of protein and fat to increase gluconeogenic substrates available 4. Lipolysis increases—> FA increase to 2mmol/L 5. Decrease in insulin and increase in anti-insulin effects prevents cells using glucose—> FA metabolised 6. Glycerol from FA —> gluconeogenesis (less need for protein breakdown) 7. Liver produces ketone bodies—> brain utilises—> reduces need of protein breakdown for gluconeogenesis 8. Kidneys contribute to gluconeogenesis 9. Once fat stores are depleted—> protein breakdown

Answer 4

After starvation Introduction of food must be gradual Reduction in urea sythesis leads to down regulation of the enzymes involved Sudden increase in protein or AA—> ammonia toxicity

Answer 5

1st half— anabolic metabolism 2nd half catabolic metabolism Change in sensitivity to hormones

Answer 6

Accommodate the demands of the foetus and placenta Support growth Ensure foetus is supplied with the correct nutrients at the correct stage of development

Answer 7

``` 8kg Foetus 3.5kg Placenta 0.6kg Amniotic fluid 0.8kg Maternal fuel stores 3kg ```

Answer 8

Hormones Maternal insulin Foetal-placental unit—> oestrogen, progesterone and placental lactogen

Answer 9

Anabolic phase—> early pregnancy —> Increased maternal fat stores —> Small increase in level of insulin sensitivity —> Store nutrients for later Catabolic phase—> late pregnancy —> Decrease in insulin sensitivity (insulin resistance) —> Increase in maternal glucose and free FA concentration (prevent storage) —> Greater substrate availability for fetal growth

Answer 10

Placental transfer Simple diffusion down conc gradient Glucose—> principle fuel—> facilitated by GLUT1

Answer 11

Fetus controls maternal metabolism to ensure its own survival Fetoplacental unit (placenta, fetal adrenal gland and fetal liver) new endocrine entity Produce proteins that control the maternal hypothalamic pituitary axis CRH—> ACTH GnRH—> hCG (human chorionic gonadotropin) TRH—> cCT (human chorionic thyrotropin) GHRH—> hPL (human placental lactogen) Placental hormones—> Oestriol and progesterone

Answer 12

First 20 weeks Preparatory increase in maternal nutrient stores (adipose tissue) Preparation for: - Rapid growth rate of fetus - Birth - Subsequent lactation ↑ insulin --> ↑ insulin/anti-insulin ratio Promotes anabolic state--> increase storage

Answer 13

Adapts to meet increasing demands Concentration of nutrient in maternal circulation kept high by: - Reduce maternal use of glucose--> FA used instead - Delay maternal disposal of nutrients after meals - Release FA from stores built up during 1st half of pregnancy Maternal insulin levels ↑ BUT the anti-insulin levels ↑ even faster so insulin/ anti-insulin ratio falls

Answer 14

Rapid increase in the growth of the fetus and the placenta

Answer 15

Hormones that exert an anti-insulin effect on maternal metabolism Corticotropin releasing hormone --> ↑ by 1000 fold maternal anterior pituitary becomes desensitised resulting in more modest increase in ACTH and cortisol Human placental lactogen Progesterone

Answer 16

Transient hyperglycaemia after meals--> ↑ insulin resistance Overall pregnancy blood glucose becomes 10% lower since insulin levels are 1.65 % higher in fasting and 3% higher in postprandial state Hypoglycaemia can occur between meals and at night because continuous fetal draw of glucose

Answer 17

Increased appetite--> more glucose ingested Oestrogen and progesterone increase sensitivity of maternal pancreatic β cells to blood glucose --> β cell hyperplasia and hypertrophy Increased insulin synthesis and secretion If β cells do not respond normally--> blood glucose seriously elevated --> gestational diabetes

Answer 18

Decrease in insulin/anti-insulin ratio and increased availability of FA from mobilisation of maternal adipose --> ketone body production in maternal liver--> fuel for developing fetal brain

Answer 19

Pancreatic β cells do not produce enough insulin Blood glucose levels rise--> gestational diabetes After birth, decreased metabolic demand and normalisation of hormones --> pancreas can respond adequately and diabetes disappears However more likely to develop type 2 diabetes in life

Answer 20

- Autoantibodies similar to those characteristic of type 1 DM - Genetic susceptibility similar to maturity onset diabetes - β-cell dysfunction in setting of obesity and chronic insulin resistance

Answer 21

Affects 3-10% pregnancies Increased incidence of miscarriage Incidence of congenital malformation 4x higher Fetal macrosomia--> large body --> increased amount around shoulder and chest--> shoulder dystocia Associated with hypertensive disorders of pregnancy such as Gestational hypertension and Preeclampsia Risk of complications reduced if diagnosed and managed

Answer 22

High blood pressure | Protein in urine

Answer 23

Age >25yrs --> insulin resistance increases with age (fat:lean mass ratio increases) BMI >25kg/m2 Race/ethnicity--> Asian, Black and Hispanic ethnic groups more common Personal or family history of diabetes Family history of macrosomia

Answer 24

Initial dietary modification including calorific reduction in obese patients Insulin injection if persistant hyperglycaemia is present : (7.5-8.0 mmol/L postprandial or >5.5-6 mmol/L) Regular ultrasound scans to access fetal growth and well being

Answer 25

Increased energy demands of skeletal and cardiac muscle--> mobilisation of energy stores Minimal disturbances of metabolic homeostasis by keeping rate of mobilsation equal to rate of utilisation Glucose supply to brain maintained End products of metabolism are removed as quickly as possible

Answer 26

Musculo-skeletal system Cardiovascular system Respiratory system Temperature regulation

Answer 27

Meet acute oxygen and fuel demands of cardiac and skeletal muscle during exercise Removal of end products of metabolism

Answer 28

Type of exercise (muscles used) Intensity and duration of exercise Physical condition and nutritional state of individual

Answer 29

Resting--> 4kJ per minute 100m sprint--> 200kJ per minute, 30kJ total 1500m race--> 140kJ per minute, 500kJ total Marathon 42km--> 80kJ per minute, 10,000kJ total

Answer 30

``` Hydrolysis of ATP ATP--> ADP + Pi + energy ATP stores are limited--> 5mmol/kg Last 2 seconds during a sprint Never falls below 20% due to regeneration Rapidly synthesised at a rate to meet demand Muslce ATP turnover -Resting 0.06 mmol/sec/kg -Marathon 1.2 mmol/sec/kg -100m sprint 3mmol/sec/kg ```

Answer 31

70% myosin ATPase | Rest on ionic gradients across the cell membrane (Na+, K+ and Ca2+)

Answer 32

Creatine phosphate --> Creatine-P + ADP --> ATP and creatine --> Immediately available--> drive contraction Glycolysis Oxidative phosphorylation

Answer 33

Muscle glycogen Blood glucose Fatty acids

Answer 34

Intensive anaerobic exercise sustained for 2 mins | Low intensity aerobic exercise susatined for 60 mins --> complete oxidation

Answer 35

1) Muscle glycogen--> glycogenolysis by glycogen phosphorylase (↑ adrenaline (phosphorylation) and ↑ AMP (allosteric regulator) 2) Glucose-6-P 3) Glycolysis --> phosphofructokinase (key regulator)--> Stimulated by ↑AMP and inhibited by ↑ATP 4) Pyruvate--> TCA cycle in aerobic conditions 5) Lactate--> end product anaerobic conditions

Answer 36

Availability not affected by blood supply No need for membrane transport into muscle cell Produce G-6-P without using ATP Mobilisation rapid--> highly branched structure

Answer 37

Liver control plasma glucose Exercise increases glycogenolysis and gluconeogenesis Liver recycles lactate produced by anaerobic metabolism (Cori cycle)--> glucose Muscles glucose uptake via GLUT4 transporter--> insulin promotes translocation and GLUT 1--> constitutively active Exercising muscle--> insulin independent pathway--> ↑AMP stimulates AMPK --> signalling cascade increase GLUT 4 translocation Rate of glucose metabolism insufficient to meet full demands in exercising muscles Blood glucose maintained for brian

Answer 38

Lactate and H+ build up Accumulation of H+ so dramatic--> exceeds buffering capacity--> impaired function and fatigue H+ inhibits glycolysis Interferes with actin/myosin interaction Causes sarcoplasmic reticulum to bind calcium --> inhibits contraction

Answer 39

Major store in adipose (some in muscle) | Enough to provide energy for low intensity exercise for 48hrs

Answer 40

1. Requires aerobic conditions 2. Slow release from adipose tissue 3. Limit carrying capacity in blood 4. Capacity is limited by uptake across mitochondrial membrane (carnitine shuttle) 5. Require more O2 per mole of ATP produced 6. Low rate of ATP production but sustained

Answer 41

10seconds Metabolic response rapid Anaerobic production of ATP -Muscle ATP and C-P used initially (5 secs) -Muscle glycogen is rapidly mobilised to provide glucose 6-P (5 secs) -Glycolysis anaerobic conditions Produces lactate (lactic acid) subsequent build up of H+ --> fatigue

Answer 42

3.5 mins Endurance as well as speed ATP--> mixture of aerobic (60%) and anaerobic (40%) metabolism of glycogen Eliminate large amounts of CO2, buffer H+ ions by muscle Three phases: - Initial--> Creatine phosphate and anaerobic glycogen metabolism -Long middle phase--> ATP produced aerobically from mucles glycogen - Final finishing--> anaerobic metabolism of glycogen and produces lactate

Answer 43

Elite 125-135 mins Carbohydrate store insufficient need to oxidise fatty acids Metabolic changes are more gradual 95% aerobic Muscle glycogen --> initial--> would last 60 mins--> carbohydrate rich diets to increase glycogen stores (best eating after exercise--> converted to glycogen not lipids) Liver glycogen--> releases glucose--> 75% from stores, 25% from gluconeogenesis Fatty acids--> utilisation increases with time 20-30mins rises

Answer 44

Endocrine--> Hormonal control Insulin levels fall slowly--> inhibition of secretion by adrenaline Glucagon levels rise Adrenaline and growth hormone rise rapidly Cortisol rises slowly

Answer 45

- Increase glycogenolysis in liver--> glycogen phosphorylase (G, A, GH) - Increase gluconeogenesis in liver (lactate and glycerol)--> PEPCK and fructose 1,6 bisphosphate (G, A, GH and C) - Increase lipolysis in adipose tissue--> Hormone sensitive lipase (G, A, GH and C)

Answer 46

Inability to maintain a given power output affecting the intensity and/or duration of exercise Caused by: - Depletion in muscle glycogen - Accumulation of H+ in muslce - Dehydration (reduces capacity for sweating, reduces heat loss, increases body temperature)

Answer 47

- Increase fuel consumption by muscles - Increased ATP production and utilisation by muscle - Increased heat production--> sweating - Increased O2 delivery to muscle --> vasodilation - Increased removal of CO2, H+ and lactate - Increased CO--> beats faster, larger stroke volume - Redistribution of blood flow away from gut and kidney to muscles - Changes in breathing--> increase rate and depth

Answer 48

Adaptation largely affect musculoskeletal and cardiovascular systems CVD --> More 2,3-bisphosphoglycerate in blood (lower affinity of Hb for O2) --> Heart beats slower for same CO SM--> increased: --> Glucose transport proteins on cell membrane (GLUT4) --> Storage of glycogen --> Potential for oxidative metabolism especially FA --> More mitochondria and more oxidative enzymes --> Number and size of muscle fibres --> Vascularisation (capillary density) of muscles--> improves O2 supply --> Myoglobin content of muscles (ability to store O2 in muscles)

Answer 49

Body composition changes ↓ adipose, ↑ muscle Glucose tolerance improves Insulin sensitivity of tissues↑ Blood triglycerides decreases (VLDL and LDL↓ and HDL↑) Blood Pressure falls Psychological effects--> well being

Answer 50

``` Physical properties and metabolic properties vary Two major fibre types --> Type I (red) and Type II (white) Long distance >70% type I Sprinters >70% type II ```

Answer 51

Speed of contraction: Slow (TI), Fast (TII) Speed of fatigue: Slow (TI), Fast (TII) Capillary supply: Good (TI), Moderate/Poor (TII) Mitochondria: Many (TI), Few (TII) Oxidative capacity: High (TI), Moderate/Low (TII) Glycolytic capacity: Low (TI), High/Moderate (TII) FA oxidation: High (TI), Low (TII) Myoglobin content: High (TI), Low (TII) Type of exercise: Low intensity, high endurance (TI), high intensity, low endurance (TII)