Endocrinology

Question 1

What does thyroxine deficiency in utero result in? Describe the disease?

Answer 1

Cretinism.
Brain damage as a result of thyroxine deficiency in utero. Screening 5-10 days post birth and if there is high TSH then thyroxine is given immediately

Question 2

What is primary hypothyroidism? Describe the pathophysiology, symptoms, treatment.

Answer 2

There is a decline in thyroxine secretion cause by autoimmune damage to the thyroid or surgical removal.

Anterior pituitary detects fall in thyroxine and secretes more TSH

SYMPTOMS: decreased metabolic rate, deepening voice, depression and tiredness, cold intolerance, weight gain and reduced appetite, constipation, bradycardia, eventual myxoedema coma
TREATMENT: essential - thyroxine replacement and monitoring TSH levels

Question 3

What is primary hyperthyroidism? Describe the pathophysiology, symptoms and treatment. What are 2 possible causes.

Answer 3

Overactive thyroid gland makes too much thyroxine and TSH falls to 0.

Possible causes: grave’s disease (autoimmune) and tumour

Features: increased metabolic rate, increased temperature, weight loss, tachycardia, mood swings, restless, insomnia, diarrhoea, increased appetite, tremor, tired and proximal myopathy, palpitations, sore eyes and enlarged thyroid

Treatment: hard to treat. Tumours removed, radioactive iodine may be used to destroy some tissue, thyroid peroxidase means iodine is less efficient activated

Question 4

What is the general peptide hormone synthesis?

Answer 4

1. Transcription from DNA forming mRNA which associates with ribosomes on the RER
2. Translation occurs and the pre-prohormome migrates to the Golgi apparatus, losing the signal peptide sequence on exiting RER becoming a prohormome.
3. In the Golgi apparatus the pro-hormone is placed into vesicles also including the necessary enzymes to cleave the pro-hormone into an active hormone
4. The vesicles of active hormone are stored near membrane and when cell is stimulated the vesicles are released by exocytosis

Question 5

What is the general steroid hormone synthesis ?

Answer 5

1. Usually cholesterol enters cells as LDL which bind to receptors and are internalised by endocytosis. Cholesterol is stored as fatty acid esters in vesicles
2. When the cell is stimulated cholesterol is liberated from esters by cholesterol esterase (activated by protein kinase A)
3. Carrier proteins such as StAR proteins which transports cholesterol into the inner mitochondrial membrane
4. Cytochrome P450 enzymes modify cholesterol forming intermediates which are further modified before final steroid hormones is produced (occurs in mitochondria and smooth ER)
5. Steroid hormones diffuse out of cell readily but as they are not highly soluble in blood they are bound to plasma proteins (particular albumin)

Question 6

Where are peptide hormone receptors located?

Answer 6

Located on plasma membrane of target cells. The hormone binds forming a complex and 2nd messenger signal in cell is triggered

Question 7

Where are steroid hormone receptors located?

Answer 7

Typically located intracellularly. The hormone-receptor complex translocation to the nucleus and act as transcription factors.

Question 8

What does the anterior pituitary do and what is it known as?

Answer 8

Adenohypophysial

The adenohypophysial hormones are all protein/poly peptide hormones and control different functions

Question 9

How is the anterior pituitary release of hormones controlled?

Answer 9

Hypothalamic nuclei ➡️ neurones to median eminence ➡️ neuro secretions (hypothalamic hormones released from neurones) ➡️ hormones diffuse into primary capillary network ➡️ carried to anterior pituitary ➡️ travel through secondary capillary network and stimulate cells in anterior pituitary to produce/release hormone

Question 10

Where are somatotrophs found? What do they produce and which hypothalamic hormones control its secretion?

Answer 10

Somatotrophs are found in the anterior pituitary

Secrete: somatotropin (growth hormone)

Hypothalamic hormones:

• somatotropin releasing hormone (stimulatory)
• somatostatin (inhibitory)

Question 11

Where are lactotrophs found? What do they produce and which hypothalamic hormones control its secretion?

Answer 11

Lactotrophs are found in the anterior pituitary

Secrete: prolactin

Hypothalamic hormones controlling:

• dopamine ( the major influence and is INHIBITORY)
• thyrothrophin releasing hormone (stimulatory)

Question 12

Where are thyrotrophes found? What do they produce and which hypothalamic hormones control its secretion?

Answer 12

Thyrotrophes are found in the anterior pituitary

Secrete: thyrotrophin (thyroid stimulating hormone)

Hypothalamic hormones controlling:
- thyrotrophin releasing hormone (stimulatory)

Question 13

Where are gonadotrophes found? What do they produce and which hypothalamic hormones control its secretion?

Answer 13

Gonadotrophes are found in anterior pituitary

Secrete: gonadotrophins:
-leutinizing hormone and follicle stimulating hormone

Hypothalamic hormones controlling:

• gonadotrophin releasing hormone (stimulatory)
• gonadotrophin inhibitory hormone (inhibitory)

Question 14

Where are corticotrophes found? What do they produce and which hypothalamic hormones control its secretion?

Answer 14

corticotrophes are found in the anterior pituitary

Secrete: corticotrophin (adrenocorticotrophin hormone ACTH)

Hypothalamic hormones controlling:

• corticotrophin releasing hormone (stimulatory)
• vasopressin (secondary stimulatory)

Question 15

How does somatotrophin mediate it’s effects?

Answer 15

It can have a direct and indirect mechanism to mediate it’s effects.

In the DIRECT mechanism the somatotrophin in the blood binds to receptors on general body tissue leading to growth and development

INDIRECT mechanism: somatotrophin binds to liver triggering the release of SOMATOMEDIANS (insulin like growth factors)

Question 16

What are the metabolic actions stimulated by somatotrophin?

Answer 16

• stimulates amino acid transport into cells
• protein synthesis stimulated
• increased cartilaginous growth
• stimulation of lipid metabolism leading to increased fatty acid production
• decreased glucose utilisation so blood glucose rises

Question 17

Describe what stimulates somatotrophin and what inhibits?

Answer 17

negative feedback: somatotrophin and somatomedin release inhibits somatotrophin releasing hormone production, increases somatostatin.
- somatostatin also inhibits somatotrophin release

stress, sleep (III and IV), oestrogens, exercise, fasting (hypoglycaemia), amino acids all stimulate the release of somatotrophin releasing hormone ➡️ more somatotrophin release

Question 18

What are the physiological effects of prolactin?

Answer 18

the main effect is breast lactogenesis in post-partum women.

other: increased LH receptors in gonads, renal na+/water reabsorption, steroid genesis, stimulates immune system

CONTRACEPTIVE EFFECT on post-partum breastfeeding women. High prolactin levels in blood leads to decreased LH from pituitary and decreased sexual behaviour.

Question 19

What neuroendocrine reflex arc leads to prolactin release?

Answer 19

suckling of breast ➡️ tactile receptors around nipple activated ➡️ afferent nerve pathway➡️ hypothalamus: dopamine inhibition and thyrotrophin releasing hormone (TRH) stimulated ➡️ prolactin secretion ➡️ milk production

Question 20

What is the posterior pituitary involved in?

Answer 20

Hormones are synthesised in the supraoptic and paraventricular nuclei in hypothalamus.
supraoptic neurones ➡️ magnocellular which are larger and pass through median eminence to posterior where they terminate
parvocellular are smaller and terminate in median eminence (used to stimulate anterior pituitary)

The neurones that terminate in the posterior pituitary secrete hormones into the blood. key hormones = vasopressin and oxytocin

Question 21

What are the main hormones secreted from the posterior pituitary?

Answer 21

vasopressin (ADH) and oxytocin

Question 22

Describe the synthesis of vasopressin. What else is vasopressin known as?

Answer 22

Pre-provasopressin ➡️ provasopressin ➡️ vasopressin

synthesis and processed in granules to form provasopressin. this is then cleaved into:
-vasopressin
-neurophysin proteins
- glycoprotein 
(formed in equimolar amounts)

Vasopressin Is also known as Anti-diuretic hormone (ADH)

Question 23

What are the actions of vasopressin?

Answer 23

Principle effect: stimulates water re-absorption in the collecting ducts - antidiuretic effect

other:

• vasoconstriction
• corticotrophin release
• effects on CNS
• synthesis of blood clotting factors
• hepatic glycogenolysis

Question 24

What are the different categories of vasopressin receptors, where are they found and what do they do?

Answer 24

V1a: arterial smooth muscle ➡️ vasoconstriction
hepatocytes ➡️ glycogenolysis
CNS neurone ➡️ behaviour and other effects

V1b: adenohypophysial corticotrophes ➡️ corticotrophin production

V1 are G protein coupled linked to phospholipase C. This generates IP3 and DAG which increases cytoplasmic calcium and other intracellular mediators.

V2: collecting duct cells ➡️ water reabsorption
Factor VIII and von willebrandt factor

V2 are linked via G protein coupled receptors to adenyl cyclase leading to ATP ➡️ cAMP which activates protein kinase A which activates other intracellular mediators.

Question 25

How does vasopressin mediate it's effects in the kidney?

Answer 25

Vasopressin binds to V2 receptors. The osmotic gradient across cell increases from tubule lumen ➡️ plasma. Synthesis of aquaporin 2 ➡️ miggration of aquapores to apical membrane and insertion of APQ2 into membrane. APQ2 acts as protein channel for H2O reabsorption into cell. APQ3 and 4 lie in basolateral membrane acting as a channel for water out of the cell into the plasma

Question 26

How is vasopressin release controlled?

Answer 26

osmoreceptors detect changes in the plasma osmolarity. Increase ➡️ more vasopressin secreted so more water is reabsorbed reducing osmolarity again Decrease ➡️ inhibits vasopressin release decreased arterial blood pressure stimulates release via reduced inhibition of baroreceptors.

Question 27

What are the effects of oxytocin? How is oxytocin release stimulated?

Answer 27

Oxytocin can lead to contraction of the myometrial cells in the uterus oxytocin leads to contraction of myoepithelial cells in the breast so milk is ejected Suckling of the nipples activated the neural afferent limbs so more oxytocin is released and the endocrine efferent limb is activated leading to milk ejection -neuroendocrine reflex arc

Question 28

What causes diabetes insipidus? What are the symptoms?

Answer 28

diabetes insipidus is caused by decreased vasopressin (ADH) meaning loss of too much water in urine. Central diabetes insipidus: caused by no vasopressing produced Nephrogenic diabetes insipidus: caused by tissue insensitivity (tissues don't recognise vasopressin) It may be caused by tumour compressing posterior pituitary or head trauma.

Question 29

What is the most common cause of primary adrenal failure in the world and the UK?

Answer 29

``` world = TB infiltrating and destroying adrenal glands UK = autoimmune ```

Question 30

What is Addison's disease? What is the treatment for an addisonian crisis?

Answer 30

Is caused by ADRENAL INSUFFICIENCY (hypocortisolism) symptoms: increased pigmentation (POMC broken down to from ACTH and MSH ➡️ stimulates melanin production); vitiligo; hypotension; weight loss and appetite loss and muscle weakness Treatment of crisis: rehydrate with normal saline, dextrose to prevent hypoglycaemia and give cortisol replacement

Question 31

What is the difference & similarities between Cushings syndrome and disease?

Answer 31

The cushings syndrome and disease are both characterised by hypercortisol (TOO MUCH CORTISOL) cushing syndrome = unknown cause cushing disease = pituitary adenoma

Question 32

What are the symptoms of hypercortisol? (cushings)

Answer 32

- impaired glucose tolerance (diabetes) - weight gain and fat redistribution to be more central - thin skin, easy bruising, slow healing - buffalo hump - facial hair and acne - stretch marks - proximal myopathy - mood changes (depression) - osetoporosis - hypertension - moon face

Question 33

What may cause excess cortisol?

Answer 33

- steroids - pituitary dependent cushings (pituitary adenoma) - ectopic ACTH (lung cancer) - adrenal carcinoma/adenoma

Question 34

What is Conn's disease?

Answer 34

An adenoma in the adrenal cortex resulting in EXCESS ALDOSTERONE ➡️ symptoms are hypertension that is resistant to treatment, oedema and low potassium

Question 35

How are sperm formed from a germ cell?

Answer 35

Germ cell ➡️ spermatogonia ➡️ primary spermatocytes➡️ secondary spermatocytes ➡️ spermatids ➡️ spermatozoa

Question 36

How is an ovum formed from a germ cell?

Answer 36

germ cell ➡️ oogonia ➡️ primary oocyte ➡️ secondary oocyte and 1st polar body ➡️ ovum and second polar body Primary oocyte is halted in prophase of 1st meiotic division, only during puberty under the influence of FSH does the cycle continue

Question 37

Where does spermatogenesis occur?

Answer 37

Occurs in the coiled seminiferous tubules. The spermatozoa are released into the lumen ➡️ migrate to rete testis via collecting duct before moving via vas efferentia to the epidymis where they mature and are then propelled to the urethra

Question 38

What cells make up the coiled seminiferous tubules?

Answer 38

the layer surrounding lumen (inner layer) is made up of SERTOLI cells. Outside of these LEYDIG cells lie in CLUSTERS

Question 39

What do sertoli cells do?

Answer 39

- form seminiferous tubule - intimately assoicated with developing spermatocytes. Spermatogonia are engulfed by sertoli cells and develop into 2nd spermatocytes and are released into lumen as spermatozoa - synthesis FSH and androgen receptors - in response to FSH produce various molecules including inhibin

Question 40

What do Leydig cells do?

Answer 40

- in response to LH they are the principle source of testicular androgens (mainly testosterone) - synthesis LH receptors

Question 41

Name the stages of the ovarian cycle and briefly describe what occurs during them.

Answer 41

PRE-ANTRAL FOLLICLE: developed in the absence of hormones, ovum surrounded by layers of cells EARLY ANTRAL FOLLICLE: ovum surrounded by granulosa cells and thecal cells. Follicle present LATE ANTRAL FOLLICLE: follicle increases in size, more antral filled space surrounding ovum. otherwise same as early antral GRAFFIAN FOLLICLE OVULATION: ovum released and cells from corpus luteum. The follicle is stimulated by FSH and LH so the thecal cells produce androgens. Aromatase made by granulosa cells converts androgens ➡️ 17 beta - oestradial

Question 42

Name the stages of the endometrial cycle and breifly describes when occurs in each and name the dominant hormone.

Answer 42

PROLIFERATIVE PHASE: days 6-14. Dominant hormone = oestrogen. The endometrium thickens and moistens and glands become enlarged and coil and have increased blood supply OVULATION: day 14-15 SECRETORY PHASE: day 15-28. Dominant hormone = progesterone (plus oestrogen). The endometrium becomes secretory and the gland secrete glycogen. Mucosa becomes engorged with blood MENSTRUATION: day 1-5. the endometrium becomes necrotic and sheds

Question 43

What is an oestrogen? Give examples.

Answer 43

An oestrogen is any substance (natural of synthetic) which induces proliferation changes in the endometrium. E.g. 17 beta oestrodiol (most potent and key to menstrual cycle), oestriol (main one in pregnancy)

Question 44

What other effects can oestrogens have?

Answer 44

- final maturation of follicle - induces LH sruge before ovulation - decreases sebacious gland secretion - increases plasma protein synthesis (hepatic) - stimulates osteoblasts - protective effect against heart disease and osteoporosis - stimulate proliferation of endometrium - stimulates growth of ductile system in breasts - increases renal salt absorption

Question 45

What is a progestogen? Give examples.

Answer 45

A progestogen is any substance (natural or synthetic) which induces secretory changes in the endometrium e.g. progesterone, 17 alpha - hydroxyprogesterone

Question 46

What effects can progestogens have?

Answer 46

- stimulate secretory activity of endometrium and cervix - stimulates growth of alveolar system of breasts - decreases renal absorption of salts (competitive inhibitor of aldosterone) - increases basal body temperature

Question 47

Describe what occurs in the early follicular phase.

Answer 47

Days 0-4 The end of the previous cycle so oestrogen and progesterone production is decreasing. Not enough of either hormone present to completely inhibit FSH and LH so small amounts of FSH and LH are secreted from the anterior pituitary (stimulated by GnRH from hypothalamus).

Question 48

Describe what occurs during the early-mid follicular phase.

Answer 48

Days 4-6/7 LH and FSH production increases as inhibition by steroid hormone decreases. LH receptors on THECAL cells. Binding of LH leads to androgen production The androgens move out of thecal cells and into GRANULOSA cells. Granulosa cells have FSH receptors. FSH then stimulates the conversion of androgens ➡️ oestrogens (mainly 17-beta oestradiol) via aromatase enzyme. - there is a local positive feedback system that leads to increasing levels of 17-beta oestradiol

Question 49

Describe what occurs during the mid-follicular phase.

Answer 49

Days 6-10 oestrogen levels are rising rapidly and many follicles are developing at different rates. One follicle will reach a point where it is producing enough oestrogen to stimulate it's own development without FSH - this becomes the GRAFFIAN follicle. The rising oestrogen levels inhibits (-va feedback) GnRH release from hypothalamus and FSH + LH release from pituitary. FSH decrease means all follicles (bar graffian) which are still dependent on FSH will undergo atresia so only the graffian is left. Inhibin is also produced from the ovary inhibiting FSH production

Question 50

Describe what occurs in the late follicular phase.

Answer 50

days 10-14. Usually oestrogen exerts a negative feedback on the production of FSH and LH, however in this phase when oestrodiol is at a sufficiently high level for a sufficient period of time (~36 hours) in the ABSENCE of progesterone leads to the negative feedback ➡️ postive feedback. This leads to a surge in LH stimulating final ripening and maturation of ovum leading to ovulation.

Question 51

Describe what happens in the luteal phase?

Answer 51

days 15-25 Granulosa and thecal cells form corpus luteum - produce hormones needed to maintain endometrium if ovum is fertilised. - corpus luteum produces progesterone, oestrogen and inhibin when stimulated by FSH and LH Dominance of progesterone needed for secretory activity of endometrium. If fertilisation doesn't occur then progesterone, oestrodiol and inhibin have a -ve feedback on LH and FSH leading to luteolysis and menstruation.

Question 52

Describe the hypothalamo-pituitary-testicular axis

Answer 52

hypothalamus secretes GnRH ➡️ anterior pituitary secretes LH and FSH. Sertoli cells stimulated by FSh leading to spermatogenesis - they produce inhibin which inhibit FSh system Leydig cells stimulated by LH to produce testosterone - testosterone has a direct and indirect inhibitory effect

Question 53

What are the roles of calcium?

Answer 53

- neuromuscular excitability - intracellular second messenger - intracellular co-enzyme - blood coagulation - muscle contraction - strength in bones - hormone/neurotransmitter stimulus - secretion coupling

Question 54

What hormones increase blood calcium levels?

Answer 54

Parathyroid hormone and Calcitriol [1,25 (OH2) vitamin D3]

Question 55

What hormone decreases blood calcium levels?

Answer 55

Calcitonin

Question 56

How does parathyroid hormone increase Ca2+ in the blood?

Answer 56

It increases calcium mobilization in the bone. Additionally it increases calcium reabsorption in the kidney by increase phosphate excretion. - PTH stimulates calcitriol secretion which increase calcium absorption in the small intestine

Question 57

How does parathyroid hormone act in the bone?

Answer 57

Parathyroid hormone does not directly stimulate osteoclasts. It binds to PTH receptors on osteoblasts inhibiting new bone synthesis and stimulating the release of osteoclast activating factor. This stimulates osteoclasts to reabsorb bone at an increased rate liberating calcium (done by secreting hydrogen ions and hydrolytic enzymes to break down bone matrix)

Question 58

What hormones increase parathyroid hormone secretion and by what receptor do they act?

Answer 58

Catecholamines stimulate release via beta-receptors.

Question 59

How does calcitonin decrease plasma calcium levels and what are it's stimuli?

Answer 59

ACTIONS: increase urinary excretion of calcium and inhibition of osteoclast activity. STIMULUS: increased plasma calcium stimulating parfollicular cells in the thyroid. Gastrin can also stimulate production.

Question 60

What is hypoparathyroidism? What features would be present?

Answer 60

Hypoparathyroidism can result from thyroid surgery, be idiopathic or hypomagnesanaemia (rare). - hypoparathyroidisn causes deficiencies of calcium and phosphorus compounds in the blood and results in muscular spasms FEATURES: decreased plasma calcium, increased plasma phosphate and decreased parathyroid hormone

Question 61

What is pseudohypoparathyroidism? What are the features of this pathology?

Answer 61

Pseudohypoparathyroidism is due to target organ resistance to parathyroid hormone (can arise from many underlying causes). FEATURES: decreased plasma calcium, increased plasma phosphate, increased parathyroid hormone SYMPTONS: short stature and round face, low IQ, associated endocrine disorders, subcutaneous calcification and carious bone banormalities

Question 62

What is Vitamin D deficiency? What features? What might the it result in?

Answer 62

Vitamin D deficiency can lead to rickets in kids and osteomalacia in adults. There is decreased calcification of bone matrix resulting softening of the bones - in children this can be seen as bowing and in adults may present as fractures FEATURES: low plasma calcium and phosphate but high parathyroid hormone

Question 63

What is primary, secondary and tertiary hyperparathyroidism? What effects does excess PTH have?

Answer 63

Primary = there is more PTH produced, no negative feedback e.g. adenoma Secondary = low plasma calcium and may be due to renal failure Tertiary = may be caused by initial chronic low plasma and there is no negative feedback stopping PTH production Kidneys: calcium reabsorption, phosphate excretion, polyuria, renal stones GI tract: gastric acid, duodenal ulcers Bone: bone lesions, bone rarefaction, fractures

Question 64

What do alpha cells secrete? What stimulate and inhibit the alpha cells? What effects does the products released mediate?

Answer 64

Alpha cells secrete glucagon which increase blood glucose from stores. Some GI hormones, some amino acids and sympathetic nervous activity stimulate alpha cells. Beta cells secreting insulin, somatostatin and parasympathetic nervous system stimulate beta cells. Glucagon increases hepatic glycogenesis. It also increases gluconeogenesis and lipolysis

Question 65

What do beta cells secrete? What stimulate and inhibit the beta cells? What effects does the products released mediate?

Answer 65

Beta cells secrete insulin which decrease blood glucose. Alpha cells secreting glucagon, some amino acids, some GI hormones and parasympathetic nervous system stimulate beta cells., Sympathetic nervous system and somatostatin inhibit beta. It increases insulin release so increases glycogenesis, glycolysis and glucose transport via GLUT-4 leading to blood glucose drop. - other effects: increasing amino acids, protein synthesis and decreasing lipolysis but increasing lipogenesis

Question 66

What can be measured to assess pancreatic function and why can it be used?

Answer 66

C-peptides. | C-peptides are formed when pro-hormone for insulin is cleaved to form the active hormone

Question 67

What happens during the fasted state?

Answer 67

Low insulin:glucagon ratio. Increased non-esterified fatty acids in blood.

Question 68

What happens during prolonged fasting?

Answer 68

Increased proteolysis, lipolysis and hepatic glucose output from glycogenolysis. Muscles use lipid metabolism as energy store, brain uses glucose and ketone bodies so increased ketogenesis

Question 69

What happens in the fed state?

Answer 69

In the 1st phase insulin stored released, 2nd phase is slow release as more insulin is synthesised and is prolonged. High insulin:glucagon ratio. Increased protein synthesis, decreased proteolysis and increased lipogenesis.

Question 70

What characteristics do type 2 diabetic patients present with?

Answer 70

Central adiposity, dyslipidaemia and hyperglycaemia. There are fewer osmotic symptoms than type 1.

Question 71

What occurs in insulin resistance?

Answer 71

Increasing non-esterified fatty acids. Usually enough insulin present to prevent ketogenesis and proteolysis. More triglyceride formation and cholesterol increases.

Question 72

How are iodothyronines created?

Answer 72

1. Getting iodine to the follicular cells in the thyroid and the colloid filled follicle in thyroid. - iodine absorbed in GI tract and transported to basolateral membrane of thyroid follicular cells. Iodine pumps move iodine into cell couple with sodium. Sodium moved out by Na+/K+ ATPase. - TSH regulates iodine uptake - pendrin iodine pumps on apical side move iodide into colloid 2. Iodide diffuses to follicular lumen and is rapidly oxidised to iodine free radicals. In the colloid thyroglobulin resides (formed in follicular cells then secreted into colloid). The iodine free radicals bind to the tyrosine molecules in thyroglobulin via THYROID PEROXIDASE enzyme 3. Products are monoiodotyrosine or diiodotyrosine. Thyroidal peroxidase catalyses coupling of these molecules to give tetra iodothyronine or tri iodothyronine

Question 73

Which (T3 or T4) is more biologically active?

Answer 73

T3 T4 is often converted to T3. It is the main secretory product. It can also be deiodinated at a different project to form an inactive reverse T3

Question 74

How are iodothyronines transported in the blood?

Answer 74

Thyronine- binding globulin Albumin Prealbumin

Question 75

What are the main actions of iodothyronines?

Answer 75

- increased basal metabolic rate - increase portion, carbohydrate and fat metabolism - potentiating some actions of catecholamines - interact with other endocrine systems - have effects in CNS - increase vitamin A synthesis

Question 76

What is the mechanism of action for iodothyronines?

Answer 76

T3 is cellular bioactive molecule. T4 is converted into T3. Main mechanism is genomic as it binds to the TR a receptor in nucleus. It stimulates transcription and protein synthesis increases.

Question 77

How is T4 and T3 secretion controlled?

Answer 77

Oestrogens have a stimulatory effect on thryotroph cells in anterior pituitary while glucocorticoids is inhibitory. From the hypothalamus somatostatin inhibits thyrothrophin release, thyrotrophin releasing hormone stimulates it. T3 and T4 have a negative feedback effect

Question 78

What are produced and secreted from the adrenal medulla? Give examples.

Answer 78

Catecholamines are produced. E.g. Adrenaline, noradrenaline and dopamine

Question 79

What are produced in the adrenal cortex and what are the 3 categories they can be divided into?

Answer 79

Corticosteroids. The 3 categories: - mineralacorticoids, glucocorticoids and sex hormones.

Question 80

How are corticosteroids stored and transported?

Answer 80

They are lipophilic so easily cross the cell membrane. These cannot be stored in hormones so they are stored in a bound form with plasma proteins in the blood. Only unbound is bioactive. Exist as a dynamic equilibrium. - e,.g. Cortisol: cortisol binding globulin, albumin, 10% bioactive - e.g. Aldosterone: CBG, 40% bioactive

Question 81

What is category corticosteroid is aldosterone? What are its main functions?

Answer 81

It is a mineralacorticoid Functions: - sodium reabsorption is distal convoluted tubule and cortical collecting ducts - stimulates potassium and proton secretion in distal convoluted tubule and cortical collecting ducts

Question 82

What is the mechanism of action for aldosterone?

Answer 82

Aldosterone diffuses into tubule from blood and binds to intracellular receptor called MINERALOCORTICOID RECEPTOR. The receptor-hormone complex is transported to nucleus and bunds to DNA upregulating transcription of certain proteins, - these proteins then act on ion channels on apical membrane so more sodium is absorbed - act on ion pumps in basolateral membrane to move the sodium into the blood from the tubule cells

Question 83

What is the juxtaglomerular apparatus? What does it do?

Answer 83

Afferent arteriole adjacent to ascending limb of Henle meets DCT. Smooth muscle of afforestation arteriole has secretory juxtaglomerular cells that secrete renin. Macula densa cells in ascending limbs are adjacent to secretory cells and has specialised sodium sensors. Renin release occurs did to decreased renal perfusion as to low BP, increase sympathetic activity and decrease sodium in filtrate

Question 84

What does renin-angiotensin system do?

Answer 84

Renin converts angiotensinogen to angiotensin I. Then converted to angiotensin II by ACE. leads to vasoconstriction and aldosterone production. - aldosterone then leads to sodium reabsorption and water reabsorption and blood pressure increases

Question 85

What form of corticosteroid is cortisol? What are the effects of cortisol?

Answer 85

Cortisol is a glucocorticoid Effects: - METABOLIC: peripheral protein catabolism, hepatic gluconeogenesis, increased blood glucose, fat metabolism, enhances glucagon and catecholamine - RENAL: excretion of water load and increased vascular permeability - bone growth - CNS effects

Question 86

What are corticosteroid receptors and how do they work?

Answer 86

Cortisol bind with equal affinity to glucocorticoid receptor and mineralocorticoid receptor. - as aldosterone and cortisol bind to MR there is a potential for excessive activity. To prevent this In kidney bioactive cortisol is converted to inactive cortisone by 11 beta - hydroxysteroid dehydrogenase 2 Cortisol mechanism of action is genomic leading to annexin 1 and annexin 1 receptor synthesis. Annexin 1 has a auto crime effect

Question 87

How is cortisol controlled?

Answer 87

Cortisol production is principally stimulates by corticotrophin (ACTH) - precursor POMC Corticotrophin releasing hormone and vasopressin G from hypothalamus stimulate ACTH release Cortisol has a negative feedback effect There is a circadian rhythm which is higher in the morning. Stressors also increase production

Question 88

What are ACTH receptors linked to?

Answer 88

they are linked to G-proteins

Question 89

what is myxoedema ?

Answer 89

term given for severe hypothyroidism