Endocrine Physiology

Question 1

What are some examples of steroid binding proteins? What are their 3 main functions

Answer 1

sex hormone binding globulin: glycoprotein that binds to sex hormones, testosterone and 17 beta-estradiol

transcortin binds to progesterone, cortisol, and other corticosteroids

1. Increase solubility of lipid based hormones in blood
2. Reduce rate of hormone loss in urine by preventing filtration
3. Act as a source of hormone reservoir as equilibrium changes

Question 2

Describe the neural and vascular connections between the hypothalamus and the pituitary?

Answer 2

VASCULAR connection between hypothalamus and ANTERIOR pituitary via the portal hypophysial vessels

NEURAL connection between hypothalamus and POSTERIOR pituitary

Question 3

What is the afferent stimulus for vasopressin and where is its integrating area?

Answer 3

from osmoreceptors in the hypothalamus

integrated in supraoptic and paraventricular nuciel

Ganong 17-1

Question 4

What is the afferent stimulus for thyroid stimulating hormone (via TRH) and where is the integrating area in the hypothalamus?

Answer 4

temperature receptors

Integrated in paraventricular nuclei and neighboring areas
Ganong 17-1

Question 5

Which hormones are secreted by the anterior pituitary? (6)

Which are secreted by the posterior pituitary? (2)

Answer 5

Beta-lipiotrophyin - ???
ACTH - adrenal cortex
Growht hormone - somateomedins
TSH - thyroxine
FSH - Estrogen
LH - progesterone/estrogen
Prolactin - breast

Vasopressin/oxytocin

Question 6

What are the hypophysiotrophic hormones and what do they act upon? (7)

Answer 6

Corticotrophin releasing hormone: stimulates b-LPH and ACTH
Thyrotropin releasing hormone: stimulates TSH
Growth hormone releasing hormone + Growth hormone inhibiting hormone: self explanatory
Luteinising hormone releasing hormone: self explanatory
Gonadotrophin releasing hormone: stimulates LH and FSH
Prolactin inhibiting hormone : self explanatory

Question 7

What are the 2 main functions of the thyroid gland?

Answer 7

Secrete hormone responsible for metabolism in tissues

Secrete calcitonin to regulate circulating levels of calcium

Question 8

Which between t3 and t4 are

• secreted in greater volume
• has greater biologic activity
• is primarily responsible for feedback of TSH secretion

Answer 8

T4 in greater volume
T3 greater biologic activity
T3 responsible for feedback

Question 9

Describe the processing of iodide and how it is metabolised in the thyroid?

Answer 9

Ganong’s figure 19-5 19-6 p 339

• dietary iodide absorbed in intestine
• thyrocytes use Na/I symporter (basolateral membrane) to pump in iodide (Na pumped out with Na/K atpase)
• iodide exits apical membrane via pendrin (Cl/I exchanger) to colloid where thyroid hormone synthesis occurs
• iodide oxidized to iodine and incorporated into tyrosine residues by thyroid peroxidase

Question 10

What happens to thyroid binding proteins under the following circumstances?

• hyperthyroidism
• Hypothyroidism
• Estrogens/methadone/heroin/antipsychotics
• Glucocorticoids/androgens/asparaginase

Answer 10

• normal
• normal
• high
• low

Question 11

What are deiodinases, where are they located and what do they do?

What can suppress their activity?

Answer 11

Enzymes that metabolise T4 and T3

Located in Liver/ kidneys, brain, thyroid, pituitary

Maintain formation of T3 from T4 in periphery or maintain ratios in particular tissues

Suppressed by burns/trauma/advanced cancer/cirrhosis/CKD/ MI/febrile states

Question 12

What are some states that decrease thyroid hormone secretion?

Answer 12

stress
dopamine
somatostatin
glucocorticoids

Question 13

What are the effects of thyroid hormone on the

• heart
• adipose tissue
• muscle
• bone
• nervous system
• gut
• lipoprotein
• metabolically active tissues

Answer 13

• heart : chronotropism and ionotropism by increasing beta adrenergic receptors and increase proportio of alpha-mosin heavy chain
• adipose tissue: stimulates lipolysis
• muscle: increased catabolism
• bone: promotes normal growth
• nervous system: promotes development
• gut: increased rate of carb absorption
• lipoprotein: formation of LDL receptors
• metabolically active tissues: stimulates oxygen consumption, increased BMR

Question 14

What are the main actions of parathyroid hormone?

Answer 14

• increase urinary phosphate excretion by decreasing reabsorption
• directly on bone to increase bone resorption and mobilise Ca2+
• increases the reabsorption of Ca2+ in the distal tubules
• increases the formation of 1,25-dihydroxycholecalciferol, and this ↑Ca2+ absorption from the intestine
• long term, PTH stimulates both osteoblasts and osteoclasts

Fig 21-3 p 379 Ganong’s

Question 15

What are the primary actions of 1,25-VitD2OH?

Answer 15

To increase calcium absorption from the intestine

• with increasing Ca2+ serum levels, 1,25 dihydroxycholecalciferol levels fall
• acts directly on the parathyroid gland to ↓preproPTH mRNA
• acts to increase expression of calcium absorption channels in proximal tubules
• increases expression of calbindin-D

Question 16

What is the primary action of calcitonin?

Answer 16

• To lower serum calcium/phosphate
• inhibit bone resorption (inhibits osteoclasts)
• increases calcium excretion in urine

Question 17

Where is calcium absorbed?

How much of it is filtered in kidneys vs reabsorbed?

Answer 17

Transported across brush border of intestinal epithelial cells
Binds to intracellular protein calbindinD9K to prevent disturbance of intracellular signalling

Filtered in kidneys, 98% reabsorbed (60% in proximal tubules, remainder in ascending LoH and distal tubule)

Question 18

What are the two different cell types of the parathyroid gland and what are their actions?

Answer 18

Chief cells – more abundant, synthesise and secrete PTH

Oxyphil cells – less abundant, unknown function

Question 19

Why is there increased calcium in urine in hyperparathyroidism?

Answer 19

PTH acts to increase reabsorption of calcium in distal tubules
Ca2+ excretion in urine is usually ↑ in
hyperparathyroidism because there is an increased load of filtered calcium that overwhelms reabsorption

Question 20

What physiological states stimulate (5) vs inhibit (3) secretion of PTH?

Answer 20

- PTH secretion is stimulated by
o ↓plasma Ca2+
o ↓magnesium
o β-adrenergic discharge
o ↑phosphate (indirectly by lowering Ca2+) 
o Chronic renal disease

• PTH secretion is inhibited by
  o ↑plasma Ca2+
  o ↑magnesium and severe Mg deficiency
  o Calcitriol

Question 21

What is the key mechanism for hypecalcaemia of malignancy?

Answer 21

p 382 Ganong’s
80% of patients have hypercalcaemia due to parathyroid hormone-related protein
Similar morphology to PTH
Usually found in keratinocytes, smooth muscle and teeth, but hyper-secreted in cancers of breast, kidney, ovary and skin.

Question 22

What’s the difference between lipoprotein lipase and hormone sensitive lipase?

Answer 22

lipoprotein lipase: makes more triglycerides available from VLDLs to reform fatty acids and fats in cells

hormone sensitive lipase: causes lipolysis eg. in fasting

Question 23

What are the actions of insulin in different tissues?

• Adipose
• Muscle
• Liver

Answer 23

Adipose tissue = ↑glucose entry, ↑FFA synthesis, ↑triglyceride deposition, ↑lipoprotein lipase, ↑K+ uptake

Muscle = ↑glucose entry, ↑glycogen synthesis, ↑AA uptake, ↑protein synthesis, ↓protein catabolism, ↑K+ uptake

Liver = ↓ketogenesis, ↑protein synthesis, ↑lipid synthesis, ↓gluconeogenesis, ↑glycogen synthesis
General = ↑cell growth

Question 24

What are the 3 layers of the adrenal cortex and what do they produce?

Answer 24

1. zona glomerulosa secrete aldosterone (mineralocorticoid)
2. zona fasciculata secrete cortisol (glucocorticoids)
3. zona reticularis secrete androgens

Go Fetch Rex
deeper you go, sweeter it gets

See fig 20-2 cortisol and androgens from both fascitulata and reticularis

Question 25

What are the 2 effects of ACTH on the adrenal cortex?

Answer 25

- trophic effect on adrenal cortex - acts on cells in zona fasciculata & reticularis --> (+) G protein --> increase intracellular cAMP --> convert cholesterol to cortisol

Question 26

``` 7 FACTS ABOUT THE PINEAL GLAND - where is it in relation to blood brain barrier - what does it secrete - when is it more active - what neural modulation does it have - where is this neural modulation and more! ```

Answer 26

1. is outside of the blood brain barrier 2. secretes melatonin: made from tryptophan via serotonin so contains both serotonin and melatonin 3. periodic pattern secretion: higher during night and low during day 4. postganglionic fibers which release NA mediate this cylic behaviour 5. synchrony is ultimately controlled by suprachiasmatic nuclei in hypothalamus 6. NA from postganglionic fibers (+) cAMP synthesis and hence melatonin synthesis and secretion 7. has no influence over K+ metabolism

Question 27

What are the key hormonal changes during the follicular phase of the menstrual cycle? What are the key events?

Answer 27

``` FSH ++ and LH + secretion oestrogen from theca ++ +ve feedback to increase FSH receptors FSH + oestrogen increase LH receptors LH + +ve feedback loop ``` rapid proliferation of granulossa cells theca produced: secretes oestrogen/progesterone, + highly vascular capsule by 6th day, dominant follicle arises on 14th day, follicle ruptures

Question 28

What are the key events during the ovulation phase of the menstrual cycle?

Answer 28

14th day, follicle rupture granulosa and theca cells proliferate bleeding from follicle clots clot replaced by corpus luteum

Question 29

What are the key events during the luteal phase of the menstrual cycle?

Answer 29

luteal cells secrete estrogen + progesterone which supress FSL/LH if pregnancy does not occur, corpus luteum degenerates by day 24 when corpus luteum regresses, hormonal support for endometrium withdraws and necrosis, spasm and degeneration of the walls of the arteries take place, producing menstrual flow p 401 Ganong's

Question 30

What is the role of HCG in pregnancy?

Answer 30

- prevents the endometrium from sloughing away - prevents involution of corpus luteum - exerts an interstitial cell-stimulating effect on the testes of the male foetus resulting in testosterone production in male fetuses

Question 31

What are the functions of oestrogen during pregnancy?

Answer 31

- Enlargement of uterus - Enlargement of breasts and growth of the breast ductal structure - Enlargement of female external genitalia - relaxing pelvic ligaments

Question 32

What are the functions of progesterone in pregnancy?

Answer 32

- Causes decidual cells to develop in the uterine endometrium (nutrition for the embryo) - ↓contractility of the pregnant uterus - ↑secretion of fallopian tubes and uterus to provide appropriate nutrition - Helps oestrogen prepare the breast for lactation

Question 33

What are the functions of LH and FSH in males?

Answer 33

FSH • (+) seminiferous tubules to make sperm • (+) sertoli cells to control maturation of spermatids to spermatozoa • (+) production of inhibin, acts as a negative feedback on pituitary to (-) FSH release LH • Is trophic on the interstitial Leydig cells, stimulating androgen production

Question 34

What are some key changes in pregnancy physiology - anterior pituitary - thyroid - parathyroid - uterus - circulation - respiration - urinary - immunology

Answer 34

- Ant pituitary 50% increase in size, increased secretion of CTH, TH, and prolactin - Increase glucocorticoid secretion and aldosterone secretion - 50% increase in size and production of thyroxine - enlarged PT gland and increased PTH - Ovaries and placenta produce estorgens, progesterone and relaxin - uterus, breasts, vagina and introitus enlarge - 15% increased in BMR - CO increase by 27th weak, normal in final 8 weeks - blood volume increases by 30% - minute ventilation increases, RR increases - urine production increase - decrease maternal antibody production

Question 35

What are the key physiological differences between adrenaline and noradrenaline?

Answer 35

Noradrenaline - vasoconstriction - reflex bradycardia - decreased cardiac ouptut - decreased pulse pressure - more receptors of alpha receptors Adrenaline (10%, methylated Norad) - HR and CO increases - TPR and DBP decrease - increased pulse pressure - increase cardiac output - more stimulation of beta receptors

Question 36

What are some of the physiological states that trigger renin? (4)

Answer 36

stimulated by ↓ECF, ↓BP, ↑SNS output (catecholamines) and prostaglandins

Question 37

What mechanisms trigger thirst?

Answer 37

Hypovolaemia: via baroreceptors and angiotensin II Hypertonicity: via osmoreceptors collated in subfornical area of hypothalamus to trigger thirst modulated by social/emotional triggers