The endocrine system

Question 1

homeostasis

Answer 1

ability of an organism to maintain a constant internal environment in the face of a constantly changing external environment.
to ensure homeostasis is maintained, there are 2 major communication/co-ordination systems: nervous system and endocrine system

Question 2

the nervous system

Answer 2

nerves mediate effects by releasing neurotransmitters, chemical substances that then bind to receptors and elicit an effect. these target tissues are situated very close to nerve terminals

Question 3

the endocrine system

Answer 3

‘action at a distance’ glands secrete hormones usually into the blood stream which are carried to target tissues where they will bind to specific receptors. these receptors may be located on the cell surface, within the cytoplasm or within the nucleus. binding to these receptors will elicit signal transduction- the process through which the information is communicated to the cell, allowing it to make its response. can be rapid or take longer e.g. steroid hormones- ligands for transcription factors, cell responds by altering gene expression so can take hours/days

Question 4

what are the 7 endocrine glads

Answer 4

the pituitary, the thyroid, parathyroid, testis, ovary, endocrine pancreas and adrenal glands.

Question 5

the pituitary gland

Answer 5

has significant input from the hypothalamus and the pituitary-hypothalamic axis- important regulator of endocrine function at the level of the whole organism.

Question 6

chemical nature can be classified as;

Answer 6

peptide, amine or steroid hormones

Question 7

peptide hormones

Answer 7

include glucagon and insulin which are made by the pancreas and are particularly important in regulating blood-glucose levels
adrenocorticotropic hormone (ACTH) also a peptide hormone, secreted by anterior pituitary gland acting on adrenal cortex to stimulate release of cortisol (and aldosterone to a lesser extent)
antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) are peptide hormones that regulate water balance. ADH acts on kidneys, retaining water and concentrating urine. ANP is produced by muscle cells in the atria of heart in response to high BP/volume-acts on kidneys to enhance sodium and therefore water loss.

Question 8

amine hormones

Answer 8

include noradrenaline and thyroid hormones thyroxide (T4) and triiodothyronine (T3). both ligands for receptors which act as transcription factors and alter gene expression in target cells.

Question 9

steroid hormones

Answer 9

cortisol

aldosterone

Question 10

how do hormones circulate

Answer 10

many circulate in an unbound form until they reach their target tissue. some are bound to carrier proteins

Question 11

example of unbound hormone

Answer 11

noradrenaline

Question 12

example of bound hormone

Answer 12

steroid and thyroid hormones

Question 13

purpose of having a large ‘bound fraction’

Answer 13

provides a reservoir of hormones in the blood which prevents fluctuations in blood concentration and bound hormones have a longer half life
for this reason hormones who have chronic actions e.g. changing gene expression through transcriptional regulation are normally bound

Question 14

measuring circulating hormone levels

Answer 14

diagnostic- both for condition and cause. also allows you to see if patient is responding to treatment - lab based assay; ‘immunoassay’ or ‘immunosorbent assay’

Question 15

immunoassay principles

Answer 15

need specific antibody, add fixed amount of antibody to a known amount of labelled hormone-antibody complex-measure complex. add more hormone until saturation reached (plateau). take known amount of unlabelled hormone and add to saturated mix this displaces labelled hormone and reduces signal. repeat with increasing known concentrations of unlabelled hormone and create displacement curve

Question 16

feedback control

Answer 16

hormone secreting cell usually contains some sort of sensor that allows cell to gauge its activity and alter accordingly. e.g. in pancreatic beta-cells which secrete insulin, beta cells sense blood glucose levels and secrete insulin when glucose levels rise. insulin contained in vesicle which allows rapid response. beta cells possess glucose transporters that are always present on the cell surface which allow glucose to move into cell along concentration gradient. once in cell, glucose is broken down by glycolysis to produce ATP and so ATP/ADP ratio increases. ATP modulates actin of special potassium channels (Katp) in cell membrane, inhibiting activity. activity of the se channels contribute to maintenance of RMP, so inhibition leads to depolarisation, activating voltage gated calcium channels allowing calcium influx which leads to calcium mediated exocytosis of insulin
therefore cell is both sensor and producer

Question 17

hierarchal control

Answer 17

often multiple levels of control e.g. release of thyroid hormone-
thyroid hormone is released from thyroid glad but this release is responded to by thyroid-stimulating hormone (TSH) released from anterior pituitary. release of TSH has a further level of control- its release is increased in response to the action of thyrotropin releasing hormone (TRH) produced by cells in the hypothalamus target tissue feedback can affect both TRH and TSH release.

Question 18

the pituitary gland

Answer 18

the pituitary gland is located at the base of the brain, consists of anterior and posterior lobe. it is a highly vascular tissue
posterior>arterial supply (one capillary bed draining into another)
anterior> portal venous system (important for communication with hypothalamus)
hypothalamic hormone released in first capillary bed, drains into second. controls release of hormones from the anterior pituitary. some hormones are released from the posterior pituitary lobe, these are made up of large-bodied neurosecretory cells in the hypothalamus. these neurones have long axons that reach into the posterior pituitary where they release hormones directly into primary capillary plexus

Question 19

anterior pituitary hormones

Answer 19

6 peptide hormones released by anterior pituitary gland; growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, luteinising hormone, follicle stimulating hormone and prolactin releasing hormone (GH, TSH, ACTH, LH, FSH, PRH). all controlled by a releasing factor made by hypothalamus and secreted into porta system.

Question 20

posterior pituitary

Answer 20

contains axons and terminals of large bodied neurones whose cell bodies are located in the supraoptic and paraventricular nuclei of hypothalamus. these neurones produce ADH and oxytocin.

Question 21

peptide hormones

Answer 21

secretory pathway- molecules are destined for secretion transit through ER and the Golgi. movement between these structures is within membrane bound carrier vesicles which pinch off from the ER and then fuse with Golgi. similar vesicles carry hormones to the plasma membrane where fusion allows the contents to be discharged from the cell. . in the ER, hormones undergo post translational modifications before passing into Golgi where further modifications take place to yield mature functional hormone which is now contained within secretory vesicle. once secreted, most peptide hormones are carried unbound in circulation. when they reach target tissues the exert their effect by binding to receptors and initiating signal-transduction pathways.

Question 22

amine hormones

Answer 22

all made from tyrosine or tryptophan
includes NA and A, made from tyrosine in the adrenal medulla. dopamine also synthesised from tyrosine -modulates release of prolactin. serotonin made from tryptophan in endocrine cells located throughout the gut- effects motility and secretion.

Question 23

steroid hormones

Answer 23

3 categories; glucocorticoids, mineralocorticoids, sex steroids.
cortisol; increased plasma [glucose] (PEPCK; beta adrenergic receptor)
aldosterone; salt balance/ECF volume (Na/K ATPase;ENaC)
not stored in vesicles, production can be stepped up rapidly but will still take some time, bind to steroid hormone receptors, transcription factors alter gene expression profile thus response measured in hours to days

Question 24

gene regulation

Answer 24

in mammals, regulation is positive, switched off unless required, flexible-will change with time, accounts for appearance of cell, essential process governed by ‘housekeepers’ e.g. GADPH

Question 25

thyroid hormones

Answer 25

transcription factors, gene targets include myosin etc- increases cardiac contractility ; NA/K/ATPase- increases myocardial oxygen consumption

Question 26

water and homeostasis

Answer 26

major component of the body, 2/3 of body weight, two ‘pools’ extracellular and intracellular.

Question 27

extracellular components

Answer 27

interstitial fluid (fluid bathing cells), plasma (liquid component of blood, lymph

Question 28

intracellular components

Answer 28

cytoplasm, nucleoplasm

Question 29

interstitial fluid

Answer 29

largest component of ECF, bathes cells, excess drains as lymph, solute composition very different from cytoplasm, distribution across membrane; electrochemical gradient

Question 30

plasma

Answer 30

water, solutes, proteins. pressure essential i.e. volume, drives perfusion, ECF production, carries hormones.

Question 31

osmolarity

Answer 31

amount of solute per unit volume, will drive water movement if it can, nature of solute critical for function

Question 32

water balance

Answer 32

intake and loss must be equal.
intake-food, water, metabolic
loss- exhalation, GI tract, sweating

Question 33

kidney

Answer 33

major site of regulated water loss-control amount of water secreted in the urine.
dilute-water loss
concentrated- water gain

Question 34

dehydration

Answer 34

water loss, no solute lost but volume decreases so osmolarity increases. haemorrhage; water and solute lost
osmolarity unchanged-volume decreased]

Question 35

hormones effecting water balance

Answer 35

anti-diuretic hormone, aldosterone, natriuretic factors, ANP
(sympathetic nervous system)

Question 36

ADH

Answer 36

released by posterior pituitary. synthesised in hypothalamus. ADH release triggered by activation of osmoreceptors located in hypothalamus- these receptors respond to osmolarity of the blood. the receptors are specialised cells, but will shrink when osmolarity increases. however, in osmoreceptor cells, shrinkage triggers afferent nerve impulse that activates the ADH-synthesising neurones. activate release of ADH >stimulate feeling of thirst> water intake decreases blood osmolarity. ADH has 2 effects;
VASOPRESSIVE; constricts blood vessel which increases BP only ay high concentrations.
kidney

Question 37

effects of ADH on kidney

Answer 37

KIDNEY; blood entering glomerulus is filtered which enters space within the bowman’s capsule- continuous with a system of tubes and ducts which modify water and solute content ultimately producing urine which is excreted. the nephron receives most of the filtered fluid and solutes occurring in the proximal tubule. the loop of henle is where process of fluid regulation begins. most of this loop and the distal convoluted tubule lie within the medulla of the kidney. the medullary interstitium contains a high concentration of sodium and chloride ions. the hypertonicity is used as a driving force of water reabsorption, but amount of water that is actually reabsorbed can be altered by altering permeability of the loop and distal CT to water.

Question 38

how is water permeability controlled

Answer 38

water permeability facilitated by presence of aquaporins. water channels located in apical and basolateral membranes of cells that form wall of tubules, loops and ducts, integral membrane proteins that form a channel which permit water. 6 aquaporins identified in tubules of kidney. water permeability usually highest in proximal CT and thin descending limb of LoH, due to presence of AQP-1 continually expressed at high levels. most of the parts of the nephron distal to this are relatively impermeable to water except in presence of ADH. ADH is the agonist of V2 receptor expressed on the basolateral membrane of cells in the collecting ducts. these are Gs coupled, activation leads to an increase in cAMP which ultimately results in the membrane insertion of AQP-2 channels. the insertion of these channels combined with the high osmotic pressure exerted by the medullary institium leads to significant water reabsorption.
anything which reduced blood volume will reduce BP. drop picked up by baroreceptors which has number of effects including stimulation of ADH release.

Question 39

factors effecting ADH secretion

Answer 39

increased osmolarity, blood pressure

Question 40

aldosterone

Answer 40

mineralocorticoid produced from cholesterol in adrenal cortex, ligand for hormone receptor, aldosterone controls expression of genes involved in sodium transport in the kidney.
acts on kidney to enhance sodium retention therefore enhances water retention, increases blood volume, therefore increases BP, drives increased tissue fluid formation. RAAS

Question 41

sodium transport

Answer 41

sodium is fully filtered in glomerulus but almost all (99.6%) is reabsorbed in nephron. approx. 65% of this reabsorption occurs in the proximal tubule and 25% in the loop of Henle, remainder occurring in distal tubule and collecting ducts. the reabsorption can occur in two ways; sodium ions can be transported through the cells that make up the tubules themselves, transcellular transport. this will depend on the electrochemical gradient for sodium and also requires presence of ion transporters ad channels on both apical and basolateral membranes. secondly, sodium can move in a paracellular fashion (between cells). movement governed by a combination of the electrochemical gradient for sodium and permeability of the tight junction between the cells
the effect of aldosterone on sodium reabsorption are largely confined to effects on transcellular transport

Question 42

transcellular transport

Answer 42

in proximal tubule. 2 step process beginning with sodium uptake from the tubule lumen across the optical membrane. at this stage the sodium concentration within the lumen is much higher than in the cell so movement is passive and depends on presence of apical sodium channels. depending on the part of the kidney these may be sodium coupled co-transporters or epithelial sodium channels (ENaC). the second step is the extrusion of sodium ions across the basolateral membrane. this is an active process and is mediated by the NA/K/ATPase pump. aldosterone mediates its effects on the kidney by increasing expression of both apical and basolateral sodium channels

Question 43

control of aldosterone release

Answer 43

aldosterone release is influenced by ACTH from anterior pituitary. in turn ACTH release is controlled by the release of CRH from hypothalamus. release of CRH is mainly a stress response and ACTH mainly drives the production pf glucocorticoids such as cortisol from adrenal cortex. high levels of plasma potassium also triggers aldosterone release, major control mechanism is mediated by the enzyme renin. RAAS- one of the major mechanisms for controlling BP.

Question 44

other hormones that affect water balance

Answer 44

sympathetic division of ANS- regulates filtration by controlling diameter if afferent/efferent arterioles
natriuretic peptides (atrial natriuretic peptide)- released in response t0 increase in blood volume.
increase is measures by stretch receptors located in the atria and secreted by atrial muscle cells. ANP has a number of effects, most of which mediated by activating a specific receptor which is linked to GC>activation of PKG which causes relaxation in smooth muscle cells. in the nephron, it has the effect of ducting both afferent and efferent vessels. ANP also increases blood flow to kidney medulla. this has the effect of washing out the sodium and chloride ions from the medullary interstitium and reducing drive for water uptake. ANP also reduces sodium reabsorption-promotes inactivating phosphorylation of ENaC channels. ANP inhibits release of renin and aldosterone and the combined effects of all these actions is to significantly reduce to both blood volume and BP

Question 45

fasting blood sugar range

Answer 45

2.9-6.4mmol/L

Question 46

glycated definition

Answer 46

non-enzymatic addition of saccharide groups to produce advanced glycation end products (AGE) and cannot function normally -damage which accounts for many of the problems of diabetes.

Question 47

diabetes mellitus

Answer 47

disorder of carbohydrate metabolism

Question 48

main hormones involved in regulation of blood glucose levels

Answer 48

insulin and glucagon, both secreted by the endocrine part of the pancreas which are located within structures known as islets of Langerhans (acini-exocrine, islets-endocrine)
tightly regulated to lipid metabolism, dysfunction is directly damaging to CVS

Question 49

types of cells found within pancreatic islets

Answer 49

a-cells; glucagon, b-cells; insulin, d-cells; somatostatin, f-cells; pancreatic polypeptide

Question 50

endocrine pancreas

Answer 50

highly vascular organ, allowing it to reply to secretagogues such as high glucose levels. also potentially permits pancrine actions of pancreatic hormones.

Question 51

type 1 diabetes

Answer 51

condition where pancreas fails to produce insulin, used to be fatal as people would suffer from rapid weight loss and ultimately die of acidosis. role of pancreas discovered; pancreatic extracts effective in treating condition.
other important action of insulin is maintenance of vascular integrity. normal insulin signalling upregulates expression of endothelial nitric oxide synthase eNOS. NO produced by endothelial cells acts on underlying vascular smooth muscle causing relaxation and therefore vasodilation and BP drops.

Question 52

synthesis of insulin

Answer 52

secretory protein, synthesised in association wit the rough ER. as the pre-hormone is synthesised the leader sequence is removed, and the rest of it moves through the secretory pathway including the Golgi. the C-peptide is evolved from this molecule, leaving A and B chains. both C peptide and insulin are released into the partial circulation when the secretory granules fuse I islet cell membrane role is unclear but it is stable and secreted in urine.

Question 53

feedback control

Answer 53

beta cells sense blood glucose levels and secrete insulin when glucose levels rise. beta cells possess glucose transporters which are always present on the cell surface, so glucose will move into cell driven by concentration gradient. once in cell glucose is broken down by glycolysis to produce ATP which increases ATP:ADP. ATP modulates action of K channels KATP, inhibiting activity. the activity of those channels contributes to the maintenance of RMP, inhibition leads to depolarisation, activate voltage gated calcium channels- calcium mediated exocytosis of insulin, therefore secretory cells have responded ti feedback from target cells.

Question 54

target tissues of insulin

Answer 54

muscle, adipose and liver

Question 55

what is insulin receptor an example of

Answer 55

tyrosine kinase receptor- binding of insulin to its receptor triggers an autophosphorylation of the cytoplasmic domains of the receptor on specific tyrosine residues. this activates 2 distinct cell signalling pathways; PI3 kinase and MAPK pathway

Question 56

PI3 kinase

Answer 56

responsible for most of the effects on glucose disposal. PKB also upregulates expression of eNOS, not only pathway

Question 57

MAPK

Answer 57

regulates the ‘non-glucose’ effects of insulin. this includes the mitogenic effects and the promotion of storage of fat in adipocytes. the MAPK pathways ultimately results in phosphorylation of transcription factors which alters their activity and thus the profile of genes expressed. it is through activation of PPARs many of these effects occur; PPAR gamma is considered the ‘master regulator’ of adipogenesis. it does this by increasing expression of genes involved in fatty acid uptake, esterification and storage and inhibiting genes involved I fatty acid breakdown and metabolisation. insulin through this pathway enhances both expression and activation of PPAR alpha

Question 58

glucose transporters

Answer 58

GLUT2; b-cells, also liver, kidney, gut
GLUT4; muscle, adipose
GLUT1; brain, active (allows constant uptake independent of blood [glucose])
GLUT3; further protects brain against hypoglycaemia

Question 59

insulin secretion

Answer 59

very closely follows glucose intake, tend to see peaks of release throughout the day reflecting eating patterns. also a slow flat peak of insulin release through the night. diets high in refined carbs elicit excessive insulin release which can lead to insulin resistance, closely related with obesity. can be reversed in early stages- detection is important. abdominal fat has endocrine actions which promote insulin resistance. hyperinsulinemia leads to downregulation of insulin receptors

Question 60

glucagon

Answer 60

hormone secreted by alpha islet cells, second major pancreatic regulator of carbohydrate metabolism, also has significant effects on lipid metabolism. secretion regulated by protein intake. primary target tissue is the liver where it acts to increase blood glucose levels >antagonise effect of insulin
acts in 3 different ways to increase BG levels; gluconeogenesis, ketogenesis, glycogenesis.

Question 61

glycolysis

Answer 61

process of sugar splitting that produces pyruvate and ATP. gluconeogenesis is sort of reversed glycolysis which generates glucose. rate limiting step catalysed by PEPCK

Question 62

gluconeogenesis

Answer 62

increases in response to glucagon because glucagon receptor is Gs coupled which leads to PKA activation which phosphorylates and activates enzymes involved in gluconeogenesis which further acts to increase release of glucose from the liver.

Question 63

ketogenesis

Answer 63

use of fatty acids as a source of energy. fatty acid oxidation , this pathway produces ketone bodies which are acidic. excessive production can lead to acidosis- can be fatal- associated with type 1 diabetes.

Question 64

glycolysis

Answer 64

glucose polymer, rapid access, store in liver, muscle, first target in starvation

Question 65

energy utilisation

Answer 65

glucose-immediate, stress
glycogen
gluconeogenesis from muscle protein
fat last
emergency sink especially in females

Question 66

role of ANS

Answer 66

parasympathetic system promotes insulin release-‘rest and digest’
adrenergic more complex, stress promotes glucose release, effects are both direct and indirect

Question 67

cortisol

Answer 67

enhances [plasma glucose]
mobilises AA from proteins
enhances ability of liver to convert AA to glucose through gluconeogenesis, also anti-inflammatory

Question 68

stress

Answer 68

physiological mechanism(response) which allows the body to prepare for ‘flight or fight’ -essential for survival. mediated by symp NS (inhibits p-symp such as digestion, sleep, repair). normally acute significantly impact on CVS.

Question 69

adrenal gland

Answer 69

2 adrenal glands, situated on the above the upper pole of each kidney. outermost tissue layer-cortex, inner layer-medulla. the 2 layers have different embryological origins; the cells of the cortex are derived from mesoderm, medullary tissue is derived from neural crest cells. cortical cells> classic endocrine cells, medulla cells> neuroendocrine (functions as postganglionic autonomic neurones that secrete neurotransmitter to blood)

Question 70

medulla NT

Answer 70

adrenaline and noradrenaline

Question 71

layers of cortex

Answer 71

glomerulosa (closest to surface and site of synthesis/release)
fasculata, reticularis

Question 72

cortisol

Answer 72

important role in chronic stress. during stress response you need an available energy source, adipose tissue would not normally be good as the energy is ‘inaccessible’ however constant exposure to stress leads to high cortisol levels which has the effect of reducing subcutaneous fat storage and promotes laying down of abdominal fat. this fat has an endocrine function. produces hormones such as TNF fact alpha, and resistin- promotes insulin resistance and associated with CVS problems. glucocorticoids also known to be immunosuppressive - can interfere with calcium uptake from the gut, cortisol downregulates expression of PLA2, inhibiting eicosanoid release and inhibiting NF-KB signalling

Question 73

steroids

Answer 73

ligands for TFs;
beta2 adrenoreceptor, PEPCK, also has effect on immune system, reduces lymphocyte numbers, inhibits osteoblasts, anti-inflammatory,
side effects; immunosuppression, osteoporosis

Question 74

regulation of aldosterone and cortisol release

Answer 74

cortisol release under control of hypothalamus and pituitary, referred to as the CRH-ACTH-cortisol axis. located within the paraventricular nucleus (PVN) of the hypothalamus, are small bodied neurones that secrete corticotropin-releasing hormone (CRH) into portal circulationof anterior pituitary. in response, anterior pituitary releases adrenocorticotropic hormone (ACTH) this release I mediated by CRH binding to its receptor in secretory cells of anterior pituitary. GPCR receptor coupled to GS. ACTH then acts on cells of the adrenal cortex activating PKA and including expression and increasing activity of the CYP enzymes responsible for breaking down cholesterol to give cortisol

Question 75

the adrenal medulla

Answer 75

neuroendocrine cells- neural tissue, but secreting products are released into circulation. the cells that secrete adrenaline are referred to as chromaffin cells. both adrenaline and noradrenaline are made from AA tyrosine. other cells can produce noradrenaline but only cells of adrenal medulla express enzyme phenyl-ethanolamine-N-methyl transferase which is required for conversion of NA to A. process happens in cytosol, then taken up and stored in the secretory granules ready for release in response to stimuli. adrenaline synthesis and secretion is under the control of the CRH-ACTH-cortisol axis, which leads to an upregulation of the enzymes in the synthetic pathway

Question 76

flight or fight response

Answer 76

controlled by sympathetic NS, involves heav suppression of p-symp activity. most of the effects are mediated through adrenoreceptors in the CVS. activation of beta receptors in the heart >^intracellular calcium conc and therefore contraction. (opposite happens upon activation of beta receptor in vascular smooth muscle, because ^cAMP inhibits MLCK. alpha 1 adrenoreceptors however are Gq coupled and cause contraction. when A is released into circulation, act to ^ HR and force of contraction. also cause vasodilation in blood vessels which have more beta receptors and cause constriction in vascular beds where alpha receptors predominate. this is how redistribution of blood flow is measured- vascular beds which need ^ flow during a stress response will have predominantly beta1 receptors

Question 77

general adaption syndrome

Answer 77

normal response to stress is the ‘alarm’ stage. this is a response of the organism to a stressor and will result in effects (fight or flight), mediated by A, NA and cortisol. normally response resolves itself but if stressor remains for any length of time there is no resolution and the individual is into a chronic stress situation. the alarm response is difficult to maintain- it is very costly in energy terms and cannot be sustained. prolonged exposure to such stimuli will lead to adaption; while the stressors are still being released from adrenal gland, the target cells have downregulated their response to them. appears to involve KATP channel. eventually, cellular resources become so depleted that exhaustion sets in. may result in death of organism

Question 78

thyroid gland

Answer 78

one of the largest endocrine glands in the body. concerned with control of basal metabolic rate. located in the neck, just below the Adams apple and in front of trachea. activity controlled by pituitary, produces and secretes thyroid hormones In response to action of thyroid stimulating hormone. released from anterior pituitary gland.

Question 79

the thyroid hormones

Answer 79

2 produced; thyroxine (T4) and tri-iodothyronine (T3), both derivatives of tyrosine and poorly soluble, almost entirely protein bound in the blood. T3 more potent, but more T$ produced. T4 converted to T3. protein bound increases half life.
both bound to iodine, position of iodine important for function. ligands for transcription factors. targets; myosin etc
particularly effect cardiac contractility, increase myocardial oxygen consumption, also increases sensitivity of myocardium to catecholamines, increases production and metabolism of cholesterol; risk of heart disease.