Refresher course for primary exam May 2008ENDOCRINE PHYSIOLOGY - VIVA/ESSAY QUESTIONS

1. Outline the synthesis and functions of thyroid hormones and how their secretion regulated.

2. a) State and briefly explain the physiological functions of calcium. b) Describe the regulation of plasma calcium.

3. Discuss briefly the functions of aldosterone and the role of renin- angiotensin system in the regulation of its secretion.

4. Outline the factors which are involved in the control of blood glucose levels.

5. List the effects of insulin in various tissues.

1. Outline the synthesis and functions of thyroid hormones and how their secretion regulated.

Sample answers:a) Thyroid hormone synthesis and regulation- Iodide trapped by follicular epithelium- transported into colloid against conc. gradient (energy dependent)- iodide then oxidized to iodine- tyrosine residues within thyroglobulin are iodinated to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)- MIT + DIT = T3 , DIT + DIT = T4

- thyroid peroxidase enzyme catalyst this series of reactions- produce 80% T4 and 20% T3

- exocytosis from the epithelium when needed- bind to TBG/TBPA/Alb in plasma (99.98% T4 is bound)- synthesis/release stimulated by TSH- 5 stages: absorption, trapping, organification, coupling, secretion- TSH stim. stage 2-5, thyroid gland vascularity, increase thyroglobulin.

Physiologic effects of thyroid hormones:

Target tissues Effect Mechanisms

Heart

ChronotropicIncrease number and affinity B-adren. rec.

Inotropic

Enhance response to cathecolamines.Increase proportion of alpha myosin heavy chain

Adipose tissue Catabolic Stim. lipolysisMuscle Catabolic Incr. protein breakdown

Bone DevelopmentalPromote normal growth and skeletal dev.

Nervous system Developmental Promote normal brain dev.Gut Metabolic Incr. rate of CHO absorptionLipoprotein Metabolic Stim formation of LDL rec

Other CalorigenicStim O2 consumption by metabolic active tissues.Incr. metabolic rate.

Functions of thyroid hormonesi. Metabolic effects –of BMR, O2 consumption, heat production - of CHO metabolism - catabolism of FFA - protein synthesis and breakdownii. Systemic effects – stim. of HR

- ventilation- GIT motility/secretion- CNS activity

iii. developmental effects – skeletal growth in childhood - promotional of normal brain

2. a) State and briefly explain the physiological functions of calcium.

b) Describe the regulation of plasma calcium.

a) Functions of Ca

i. Cytoplasm - excitation-contraction coupling in all muscle - excitation-secretion coupling – endocrine/exocrine fn - enzyme cofactor - regulation of mitotic activity

ii. Cell membrane - excitability of nerve and muscle membrane - automaticity of smooth muscle/SA & AV nodes - neurotransmitter release at NMJ - neurohormonal release & activity eg. alpha adr, Ach, ADH, oxytocin

iii. Extracellular - coagulation cascade I, II, VII, IX, X (haemostasis) - complement cascade - WBC chemotaxis - bone & teeth formation (Ca hydroxyapetite)

b) Regulation of plasma Ca

- [Ca] 2.20-2.55 mmol/l- 50% ionized, 40% bound, 10% non-ionised complex with citrate/PO4- most important influence on protein binding is plasma pH- alkalosis binding Ca due to exposure of more anionic sites ↓ ionized Ca- acidosis ↓ binding Ca ionized Ca- mainly 2 hormones ie PTH, Vit D

- PTH - 4 parathyroid glands, secreted by chief cells - a polypeptide, t1/2 10 min

- Ca release from bone (incr bone resorption) - reabsorption of Ca in renal tubules - urinary PO4 excretion - production of Vit D3 (indirect effect)

- Vit D - 7-dehydrocholestrol + UV light (skin) vit D3 (cholecalciferol) - diet (vit D2) - vit D3 25-D3 1,25 D3 (liver) (kidney) - stimulated by – PTH, low Ca/PO4 - uptake Ca/ PO4 from gut - reabsp. Ca/ PO4 from renal tubules - bone resorption/promotes mineralization

- Calcitonin – C cells of the thyroid (parafollicular cells) - lower Ca during episode of hyperCa - acts on bone to reduce rate of release of Ca (inhi bone resorption) - no significant role in normal Ca haemostasis.

3. Discuss briefly the functions of aldosterone and the control of its secretion.

- 95% of mineralocorticoid activity- secretion regulated by:i. RAAS - renin released by JG cells : - pressure in afferent arteriole

- flow in distal tubule detected by macula densa - sympathetic activity

AT ATI ATII ATIII (40% pressor effect) renin ACE angiotensinogenase

- ATII effects: - vasoconstriction (MAP, RPP, renin) - thirst & stim ADH - Na and H2O excretion - stim aldosterone release - sensitivity of baroreceptor reflex potentiate the pressor effect - vasopressin/ACTH release

ii. [K] (much less changes in [Na])iii. ACTH – necessary but not important in normal regulation

Functions of aldosterone:i. control of electrolyte/fluid content in the ECF- active reabsorption of Na in distal tubule- secretion of K (main negative feedback)- secretion of H (minimal)

4. Outline the factors which are involved in the control of blood glucose levels.

- normal 4-7 mmol/L- determined by balance between amount entering the blood and the amount leaving it.- main determinants: - dietary intake, renal loss (threshold 10mmol/L) - rate of entry into cells of muscle/adipose (insulin dependent) - utilization by non-insulin dependent organs eg nerves, rbcs, exercising muscle etc - glycostatic activity of liver- after meal – glucose level insulin release entry of glucose into liver (glycogen, oxidation), muscle (glycogen), adipose (glycerol)- fasting - glucose level insulin glucagon glycogenolysis, gluconeogenesis in the liver release of glucose

Other neural-hormonal factors:Cortisol – permissive role, required for glucagons/adrenaline activityCatecholamines – hepatic glycogenolysis, lipolysis GH – inhibit uptake of glucose by muscle cells, glucose release by liverThyroid hormones – GIT absorption, glycogen synthesisOestrogen/progesterone/HPL – insulin resistanceSomatostatin – inhibit release of insulin/glucagons

Sympathetic – by hypoglycaemiaHypothalamus – appetite centre

5. List the effects of insulin in various tissues.

- anabolic hormone, polypeptide with 2 chains linked by disulphide bond- t1/2 5 min, internalized after binding to rec.- 80% degraded by liver and kidney

- Principal actions of insulin:i. rapid (seconds) - transport of glucose, amino acids and K into insulin

sensitive cellsii. intermediate (min) - stim of protein synthesis - inhi og protein degradation - activation of glycolytic enzymes and glycogen synthase - inhi of phosphorylase and gluconeogenic enzymes

iii. delayed (hrs) - in mRNA for lipogenic and other enzymes

Effect of insulin in various tissues

Adipose tissue

glucose entry fatty acid synthesis glycerol phosphate synthesis triglyceride depositionactivation of lipoprotein lipaseinhibition of hormone sensitive lipase K uptake

Muscle

glucose entry glycogen synthesis amino acid uptake protein synthesis in ribosomes protein catabolism release of gluconeogenic a.a ketone uptake K uptake

Liver

ketogenesis protein synthesis lipid synthesis glucose output

General cell growth