6.2 Endocrine Flashcards
Hypothalamic & pituitary hormones
type
are they stucturally similar to steroid
What receptors do they interact with
What are they polypeptides
what are the glycoprotein
What are used in Rx prostate Ca
The hypothalamic and some pituitary hormones are typical examples of peptide hormones.
They are chains of amino acids or peptides and are structurally dissimilar to the steroid derived hormones. Unlike the steroids, the majority of peptide hormones are lipophobic and interact with cell surface receptors.
These peptides have autocrine, paracrine as well as endocrine effects.
Adrenocorticotrophic hormone (ACTH)
Growth hormone (GH) and
Prolactin
are simple polypeptides or proteins, whereas
Thyroid stimulating hormone (TSH)
Luteinising hormone (LH) and
Follicle stimulating hormone (FSH)
are glycoproteins.
Luteinising hormone releasing hormone (LHRH) analogues are a well established treatment for prostate cancer.
Peptide hormones can be synthesised using DNA techniques, for example, LH, FSH and growth hormone releasing hormone (GHRH).
Carbimazole used for what
what is a/w
Carbimazole is used in the treatment of thyrotoxicosis in pregnancy.
It is allegedly associated with aplasia cutis but it is contended that this disorder may be more associated with thyrotoxicosis per se than the drugs.
Thionamides are used in thyrotoxicosis for variable periods from six months up to two years, but irrespective, recurrence of thyrotoxicosis following withdrawal is of the order of 70%.
Carbimazole is secreted in milk
Skin rashes due to carbimazole are unlikely to recur if therapy is changed to propylthiouracil
Symptomatic hypocalcaemia following subtotal thyroidectomy is generally transient
Calictonin -
What type of hormone
where is it relased from
what does it repond to
how its effects mediated
secreted in excess in what
Calcitonin is a polypeptide hormone released from the C cells of the thyroid in response to hypercalcaemia (not hypocalcaemia).
Its hypocalcaemic effects are mediated by preventing bone resorption by osteoclasts.
It is secreted in excess in patients with medullary carcinoma of the thyroid.
Post operative hypergylcaemia
Most likely d/t
Increase in
Effect on insulin
Hyperglycaemia is a significant early feature of the metabolic response to trauma and surgery. It results from an increase in glucose production and decreased glucose utilisation bought about by neuroendocrine stimulation. There is an increase of:
Catecholamines ACTH and cortisol Glucagon, and Growth hormone. There is also inhibition of insulin from the beta cells of the pancreas and a decrease in insulin sensitivity peripherally. The net result of these changes is hyperglycaemia.
Unless high dose opioids or central neuraxial block is used as part of an anaesthetic the “stress response” to even endoscopic surgery will not be prevented.
Pituitary glad is where
lies near what
divided into what
Anterior secretes what
Posterior secretes what
The pituitary gland lies in the pituitary fossa which is located in the sphenoid bone and lies close to the floor of the third ventricle. It can be functionally divided into anterior and posterior lobes.
The anterior lobe secretes the following:
Growth hormone Prolactin Adrenocorticotropic hormone (ACTH) Thyrotropin Lutenising hormone (LH), and Follicle stimulating hormone (FSH). The secretion of these hormones is controlled by releasing and inhibitory factors released by the hypothalamus.
Oxytocin and vasopressin are secreted from the posterior lobe (not anterior) of the pituitary.
Vasopressin (antidiuretic hormone) is a neuropeptide which is synthesised in the cell bodies of the supraoptic and paraventricular nuclei (not in the pituitary). It is then transported down their axons to the posterior lobe of the pituitary gland from which it is secreted.
Iron is required for what
what is the total iron inb ody
where are the greatest stores
Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses.
There are 35-45 mg/kg iron in the adult body (about 4-5 g)
Iron is present in the following forms:
Haemoglobin 65% Ferritin and haemosiderin 30% Myoglobin 3.5% Haem enzymes 0.5% Transferrin bound proteins 0.1%
Adh inhibited by x5
increased by x3
Antidiuretic hormone (ADH) secretion is inhibited by:
Dilution Cold Hypertension Alcohol Tetracyclines.
Secretion is increased by:
Barbiturates
Selective serotonin reuptake inhibitors (SSRIs) and
Sulphonylureas.
Kidney manufactures what hormones
how is aldo released
what happens to cholecalciferol
The kidney is responsible for the manufacture of renin which acts on the circulating peptide angiotensinogen to convert it to angiotensin I which is then further cleaved in the lungs to angiotensin II.
This acts on the adrenal cortex to release aldosterone.
Cholecalciferal is hydroxylated to 25-hydroxycholecalciferol by the enzyme 25-hydroxylase in the liver.
Within the kidney, 25-hydroxycholecalciferol serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form.
The kidney also forms 1,25-dihydroxyvitamin D (hence hypocalcaemia in chronic renal failure) and is also responsible for the synthesis of erythropoietin.
Aldosterone is synthesised by the adrenal cortex.
How is pituitary connect to hypotahl
where is it
what is produced by anterior pit
is hormone production constant same
The pituitary stalk connects the posterior pituitary to the hypothalamus and it is contained in the pituitary sella with the optic chiasm and hypothalamus as superior relations.
Glycoproteins such as thyroid-stimulating hormone (TSH) and luteinising hormone (LH) follicle-stimulating hormone (FSH) are produced by the anterior pituitary. These share a common alpha subunit with unique beta subunits.
There is diurnal variation in the secretion of many hormones such as LH, adrenocorticotropic hormone (ACTH) and growth hormone (GH).
Gproteins are what
what type of receptors are they
regulate what
How is EPO created
G Proteins are cytoplasmic proteins intimately related to the cell surface receptor and are involved in the cell signalling process such as occurs with hormone receptors.
The G protein or metabotropic receptors may be stimulatory or inhibitory and notably are involved in the regulation of adenylate cyclase.
Erythopoietin acts on type I cytokine receptors (EPoR) on the cell surface of red blood cells and which influence tyrosine kinase activity. The primary role of erythropoeitin is to reduce red-cell precursor death.
Aldo
what type
prod where from what
accounts how much of mineral activity
production controlled by
main site action
Aldosterone is a steroid hormone produced in the zona glomerulosa by cleavage of corticosterone to aldosterone.
Aldosterone accounts for approximately 95% of the mineralocorticoid activity produced by corticosteroids.
This is under the influence of ACTH, potassium and angiotension II concentrations.
The main site of action is the principal cells of the distal convoluted tubule and collecting duct
Glycolysis - where
what is ther energy return
Pyruvate
what happens to it
which then enters what
where does this happen
what is the aim of the elctron tranpsort phosphorylation
what is net energy
anaerobic resp
Glycolysis occurs in the cytoplasm and converts 1 glucose molecule (6-carbon) to pyruvate (two 3-carbon molecules). It produces 4 ATP molecules and 2NADH but uses 2 ATP in the process. The net energy production is 2 ATP.
Pyruvate is then oxidised to acetyl coenzyme A (generating 2 NADH per pyruvate molecule), which then enters the Krebs cycle (citric acid cycle). This takes place in the mitochondria and produces 2 ATP, 8 NADH and 2 FADH2 per glucose molecule.
The aim of electron transport phosphorylation is to break down NADH and FADH2 and pump H+ into the outer compartment of the mitochondria. This process occurs in the mitochondria.
Electron transport phosphorylation typically produces 32 ATP. Net energy production is 36 ATP.
Anaerobic respiration occurs in the cytoplasm and pyruvate is reduced to NAD producing 2 ATP.
Post pit hormones
Manufactured in the hypothalamic nuclei, antidiuretic hormone (ADH) and oxytocin are secreted from the posterior pituitary.
IGF-1 is mostly produced under the influence of growth hormone by the liver.
Peptide hormones
how do they nice
what effects
can they rx prostate ca
how are they synth
Typical examples of peptide hormones include hypothalamic and some pituitary hormones and are chains of amino acids which are structurally dissimilar to the cholesterol-derived steroids.
Unlike the steroids, the vast majority of peptide hormones are lipophobic and interact with a cell surface receptor.
These peptides have autocrine and paracrine as well as endocrine effects.
Luteinising hormone-releasing hormone (LHRH) analogues are a well established treatment for prostate cancer.
Peptide hormones are synthesised through deoxyribonucleic acid (DNA) techniques, for example luteinising hormone/follicle-stimulating hormone (LH/FSH), growth hormone-releasing hormone (GHRH).
How many zones adrenal cortex?
what are they
what do they produce
main secretion of
There are three zones of the adrenal cortex. They are as follows:
Zona glomerulosa (the outermost layer) produces the mineralocorticoid aldosterone
Zona fasciculata produces the glucocorticoids, cortisone, corticosterone and deoxycorticosterone (the most physiologically active and prolific gluclocorticoid is cortisol)
Zona reticularis produces androgens, dehydroepiandrostenedione (DHEA), DHEA sulphate and androstenedione.
The main secretion of the medulla is epinephrine with a small amount of norepinephrine. The adrenal gland tissue is considered as modified post-gangionic neurones.
Catecholamine release is mediated by preganglionic sympathetic nerve fibres from the thoracic spinal cord (T5-T11). Catecholamine release is mediated by cholinergic nicotinic transmission.
A portal (venous) system is one that connects two capillary beds. The two portal systems in the body are the hepatic and hypophyseal. No such system exists in the adrenal cortex.
ADH made where
release where
how is it released
where does it act
Nictoine affect
Antidiuretic hormone (ADH) in synthesised in the supraoptic nucleus of the hypothalamus as part of a large precursor molecule. This molecule is transported to the posterior pituitary where it is released.
Osmoreceptors in the hypothalamus detect alterations in plasma osmolality. The receptors regulate the release of ADH.
Water excess in the plasma causes a decrease in plasma osmolality, whilst water deficiency causes an increase in plasma osmolality. An increased osmolality leads to an increase in ADH secretion. A decreased osmolality causes a decrease in ADH secretion.
ADH acts on V2 receptors (a G coupled receptor), leading to the activation of adenylate cyclase. This activates a second messenger system that leads to the incorporation of water channels (aquaporin-2) into the apical membrane of collecting ducts increasing water permeability and hence water retention by the kidneys.
The release of ADH is also stimulated by nicotine.
TSH measures
What is most frequent reason for elevate TSH adequate thearpy
Serial TSH measurements are used to determine the adequacy of treatment with thyroid hormones in patients with an intact hypothalamic-pituitary axis. Change in TSH levels lag behind changes in T3/T4 levels becoming apparent after approximately eight weeks of therapy with thyroid hormone replacement.
The most frequent reason for persistent elevation of serum TSH in patients presumed to be taking adequate thyroid replacement therapy is poor compliance. Typically, a patient who does not regularly take their L-thyroxine will try and “catch up” prior to a visit to a clinician for a blood test.
Reduced responsiveness occurs why
How many types
Reduced responsiveness of target tissues to thyroid hormone or resistance to thyroid hormones (rTH) occurs due to mutations in the thyroid hormone receptor β gene. The syndrome occurs as a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone. There are two types:
Generalised resistance (GrTH) Pituitary resistance (PrTH)
Patients with RTH have elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations with normal or slightly elevated serum thyroid stimulating hormone (TSH) level.
Tissue-level unresponsiveness to thyroid hormone is rare and is caused by mutation in the gene that controls a receptor for T3. Drugs that increase metabolism of thyroxine include:
Rifampin Phenobarbital Phenytoin St John's Wort Carbamazepine Warfarin These drugs lower circulating thyroid hormones and would be associated with a raised TSH but low T3/T4.
What is the biggest expenditure of energy
increase with what
is it related to leptin
The basal metabolic rate (BMR) is the single largest component of energy expenditure.
It
Is higher in males than females
Increases with increased muscle, that is, lean tissue
Declines with age
Is unrelated to serum leptin.
Leptin is the hormone released from adipose that regulates appetite.
Hypercalcaemia - caused by
most commonly
less common
Hypercalcaemia is commonly caused by hyperparathyroidism and malignant tumours (especially bone secondaries).
Less common causes include
Milk-alkali syndrome Hyperthyroidism Sarcoidosis Adrenocortical insufficiency Immobilisation Thiazide diuretics
Stress response to surgery
Physiological effects of surgery include:
1 Antidiuresis (increased ADH secretion in an effort to retain water and increase the blood pressure)
2 Increased catecholamine, cortisol and aldosterone secretion (increased sodium retention and increased potassium loss) and
3 Increased nitrogen excretion.
4 There is decreased utilisation of glucose as a consequence of the excess secretion of cortisol and catecholamines.
Cortisol, whilst promoting gluconeogenesis it increases glycogen synthesis but more importantly has an anti-insulin effect by inhibiting glucose transporters decreasing peripheral utilisation of glucose (glucose not entering cells). Catecholamines also inhibit insulin-mediated glycogenesis.
What ar the principle thyroid hormones
What hormone causes release into circulation
what is the ratio
which is active
Triiodothyronine (T3) and thyroxine (T4) are the principal thyroid hormones produced (THs), stored and secreted by the thyroid gland.
Thyroid stimulating hormone (TSH) from the anterior pituitary gland stimulates the release of T4 and T3 into the circulation. The ratio T4 to of secreted T3 is in the order of 200:1. Serum T4 is 40-fold higher than T3. However, only 0.03% of T4 is unbound to plasma proteins and therefore unavailable to diffuse into the target cells compared with 0.3% unbound T3. A majority of circulating T3 results from 5′-deiodination of the outer ring of T4 by deiodinases.
Type I deiodinase is found in peripheral tissues such as liver and kidney and is responsible for the conversion of the majority of T4 to T3 in circulation. Type II deiodinase is found in brain, pituitary, and brown adipose tissue and primarily converts T4 to T3 for intracellular use.
Reverse T3 (rT3) is an isomer of T3 and is inactive. It differs from T3 in that the missing deiodinated iodine is from the inner ring of the thyroxine molecule compared with outer ring on T3. In some conditions an excessive production of rT3 can lead to competition for the 5′-deiodinase enzyme system leading to less peripheral conversion of T4 to T3.
The T3 molecules are further processed by decarboxylation and deiodination for the production of iodothyronamine (T1a) and thyronamine (T0a) respectively. These are also inactive metabolites.
