hubs module 4 - endocrine

what is the concentration normal range in ECF for blood glucose

3.5 - 6mmol/L fasting

3.5 - 8 mmol/L non fasting

what is the concentration normal range in ECF for sodium (Na+)

135-145 mmol/L

what is the concentration normal range in ECF for calcium (Ca2+)

2.2-2.6 mmol/L

what is the concentration normal range in ECF for potassium (K+)

3.5-5 mmol/L

what is the concentration normal range in ECF for ECF osmolarity

275-300 mosmol/L

regulated variable

the variable the system senses and tries to keep stable e.g. blood glucose, BP

set point

the target value for the variable e.g. BGL 5mmol/L etc...

reference range

values of regulated variables within 'normal' limits

components of a negative feedback loop

1) sensors - monitors variables, detects changes from set point

2) control centre/integrator - compares the actual value to the set point

3) communication pathways - signals sent along if correction is needed

4) effectors - oppose the effect of stimulus which restores variable to set point

negative feedback

opposes change and moves regulated variables back towards their set point

positive feedback

a response to a stimulus that moves the variable further away from the set point

examples of positive feedback

blood clotting, childbirth, lactation

feed forward homeostatic control

involves anticipation of conditions that could disrupt homeostasis if some sort of preemptive action was not taken e.g. putting on jacket because it looks cold

paracrine hormone

local hormone that acts on neighbouring cells

autocrine hormone

affects the same cell that secretes them (local hormones)

what are catecholamines and what do they do

dopamine, noradrenaline, adrenaline

derived from tyrosine amino acid

what hormone are thyroid hormones derived from

2x tyrosine (fat soluble)

what does tryptophan amino acid derive into

melatonin anf serotonin

how is histamine made

derived from histidine amino acid

what is a peptide hormone made of and is it water soluble

chain of 3-49 amino acids, yes its water soluble

- not produced in active form, undergoes processing in golgi apparatus first

what is a protein hormone made of and is it water soluble

chain of 50-200 amino acids, yes it is water soluble

- not produced in active form, undergoes processing in golgi apparatus first

what are lipid derivative hormones

steriod hormones

- generally synthesised as needed

- derived from cholestorol therefore lipid soluble

steroid hormones

- derived from cholestorol

- bound to specific transport proteins in the blood so remain in circulation longer than peptide hormones

what are the classes of hormones

amino acid derivatives, peptide and protein hormones, lipid derivitives

in order for hormones to have an effect on the target cell, what must they do first?

bind to receptors on the target cell

- membrane for water soluble hormones

- cytoplasm or nucleus for lipid soluble hormones

how do steroid hormones exert their effects

- diffuse from blood through lipid bilayer into cytoplasm

- bind to receptors in cytoplasm or nucleus

- activated receptor hormone bunds to steroid response elements

- changes gene expression by switching genes on or off

- creates new mRNA which has an altered structure and function

how do thyroid hormones exert their effects

- diffuses from blood, through lipid bilayer and into mitochondria or nucleus

- binds to receptors on mitochondria or nucleus

- binding to mitochondria increases energy production

- binding to nucleus alters gene expression (cell structure and function)

how do water soluble hormones exert their effects

- binds to receptors on cell surface (acts as first messenger)

- the receptor is a g coupled receptor which causes the production of a second messenger inside the cell

where are protein and peptide hormones synthesised

on the ribosomes of the rough ER

how are proteins and peptides synthesised in the RER

1. 1st enter as larger preprohormones that arent biologically active but may contain aa sequences of peptides that are

2. cleaved to form smaller prohormones in the ER

3. Then packaged into secretory vesicles in the golgi apparatus, during this enzymes in the vescicles cleave prohormones to produce active hormone and inactive fragments which are secreted via excytosis

g protein coupled receptors

transmembrane proteins with 7 membrane spanning domains

what can an activated g protein subunit do

activate enzymes on inner cell membrane (adenylate cyclase) to produce a second messenger (cAMP) or alter ion channel activity

What is the role of second messengers like cAMP or Ca2+ in GPCR pathways?

they switch off various enzymes within the cell

where is the pituitary gland located

sella turcica of the sphenoid bone

base of the brain

inferior to hypothalamus

what are the different parts of the anterior pituitary

pars distalis (larger inferior part)

pars tuberalis (wraps around infundibulum superiorly)

what are the different parts of the posterior pituitary

pars nervosa - larger bulbar portion

infundibulum - connects with the hypothalamus

what tissue type is the anterior pituitary derived from

epithelial tissue

what is the posterior pituitary derived from

neuroectoderm

what 3 things can different groups of neurons in the hypothalamus do

1. control secretion of anterior pituitary via releasing hormones (RH) and release inhibiting hormones (RIH)

2. synthsise hormones secreted by posterior pituitary

3. directly control secretion of cells in the adrenal medulla

describe the hypothalamic-hypophyseal portal system

rh and rih are secreted from the hypothalamic neurons in region of median eminence, diffuse into primary capilliary plexus, travel in portal vessels to secondary capillary plexus, diffuses into anterior pituitary cells then enter systemic circulation through anteiror hypophyseal veins

what os the median emenence

the nucleus at the base fo the hypothalamus where rh enters the hypothalamo-hypophyseal portal system in order to be transported to the pituitary gland

how do hormones from anterior pituitary cells enter systemic circulation

throughthe anterior hypophyseal veins

oxytocin

a peptide hormone synthesised mostly in neurons of paraventricular nucleus (PVN)

where is oxytocin stored

in the nerve terminals of the posterior pituitary

what does oxytocin do

increase contraction of the uterus during labor and stimulates the ejection of milk into the ducts during lactation

what is ADH - antidiuretic hormone

acts on kidneys to block water movement into the urine and controls concentration of water in body fluids as well as blood pressure

where is adh stored

posterior pituitary gland

how does adh respond to increased ecf osmolarity

1.change detected by osmoreceptors in hypothalamus

2. osmoreceptors signal neurosecratory cells which trigger APs and release of adh from post. pit.

3. adh diffuses into capilliary plexus and travels to kidneys

4. it binds to receptors on colelcting duct cells in kindey, increasing water reabsorption

5. ecf osmolarity restores

what are the 2 types of diabetes insipidus

neurogenic and nephrogenic

neurogenic diabetes insipidus

insufficient adh secretion

- may occur following trauma, injury or infection in hypothalamus or post. pit.

- large volumes if dilute urine due to reduced water reabsorption in kindeys

nephrogenic diabetes insipidus

kindeys dont respond to adh

- genetic

- medication induced

- secondary to renal disease

what happens to adh levels if you take drugs such as mdma

triggers inappropriate release of adh and serotonin, causes you to drink more water and overhydrate

this dilutes ecf so osmolarity of cells will combat this by bringing water into cells causing swelling

what hormone do somatotrophs produce

growth hormone - ant. pit.

what hormone do thyrotrophs produce

thryoid stimulating hormone ant. pit.

what hormone do gonadotrophs produce

follicle stimulating hormone and lutenising hormone - ant. pit.

what hormone do lactotrophs produce

prolactin ant. pit.

what hormone do corticototrophs produce (full name)

acth - adrenocorticotrophic hormone - ant. pit.

when hypothalamus releases TRH what is the effect on the ant. pit.

releases tsh

when hypothalamus releases CRH what is the effect on the ant. pit.

releases acth

when hypothalamus releases GHRH what is the effect on the ant. pit.

releases growth hormone

when hypothalamus releases GHIH what is the effect on the ant. pit.

inhibition of growth hormone release

when hypothalamus releases GnRH what is the effect on the ant. pit.

releases lh and fsh

when hypothalamus releases PRH what is the effect on the ant. pit.

releases prolactin

when hypothalamus releases PIH (dopamine) what is the effect on the ant. pit.

inhibition of prolactin release

what does growth hormone do

promotes increased size of cells, number of cells, size of muscle, bone, cartilage

how does growth hormone affect children

increases the growth rate of skeleton and muscles

how does growth hormone affect adults

maintains muscle mass and bone mass and promote healing of injuries as well as tissue repair

how does hGH cause growth and metabolic effects

secreted by ant. pit. causes liver to produce insulin-like growth factor 1 (igf1) which causes growth and metabolic effects

somatomedins

insulin like growth factors

what are the metabolic effects of growth hormone

1. promotes growth and protein synthesis when nutrition state is favourable

2. switches cell metabolism towards use of lipids as energy source

3. weakens some of insulins actions

3 growth hormone disorders

dwarfism

gigantism if excess gh before epiphyseal plates fuse

acromegaly if excess gh after epiphyseal plates fuse

2 features of thryoid gland

- composed of follicles

- secretes thyroid hormone

2 thyroid hormone names

thyroxine (t4) and triiodothyronine (t3)

which of the 2 thyroid hormones is more abundant in the BLOOD

t4 - thyroxine

which of the 2 thyroid hormones is more abundant in the TISSUE

triiodothyronine (t3)

what is thryoglobulin

stores thyroid hormones in the follicle

what are parafolicular cells (c cells)

thyroid cells that secrete calcitonin and regulates calcium - reduces OC activity and inhibits reabsorption of ca by kidney

calcitonin

hormone thats secreted by the thyroid that has the effect of lowering blood calcium

basal metabolic rate

the amount of energy per unit time required to keep the body functioning at rest

how does thyroid hormone affect your bmr

it increases it

what is thyroid hormone important for?

neurological and physical development

what causes infantile hypothyroidism

-absent or poorly functioning thyroid gland

- poorly functioning pituitary

- lack of iodine in mothers diet during development

effects of infantile hypothyroidism

-low basal metabolic rate

- delayed growth and neural development

- swelling around eyes and tongue

what can cause a decreased amount of thyroid hormone in the body

absent or poorly functioning thyroid gland, poorly functioning pituitary or hypothalamus

causes of adult hypothyroidism

- goitre

- iodine deficiency or low levels of thyroid hormones

- high tsh = excessive growth of thyroid tissue

- autoimmune diease e.g. hashimotos thyroiditis

simple goitre

enlargement of thyroid gland causing adult hypothyroidism, not associated with any other disease process

how does autoimmune disease cause adult hypothyroidism

immune cells attack own thyroid gland, thyroid swells and produces less thyroid hormone than usual

hyperthyroidism

commonly caused by graves disease, antibodies attach to tsh receptors and stimulate overproduction of thyroid hormone

how is calcium regulated in the body

- bones act as resevoirs (OBs and OCs)

- most of ca stored in bone is stored as hydroxyapatite

- kindeys (urine conc of calcium)

short term effects of calcium exchange between bone and ecf

calcium dissociated from CaHPO4 in bone to ca + HPO42- in ecf

parathyroid glands

4-8 small glands embedded int he psoterior surface of the lateral lobes of the thyroid gland

- secretes parathyroid hormone (protein hormone) in response to low ecf calcium conc

2 types of parathyroid cells

cheif cells/principle cells

oxyphil cells

what do chief/principle cells do

produce parathyroid hormone (pth)

what do oxyphil cells do

not present before puberty

help with identification of parathyroid tissue from thyroid tissue

what factors of osteoblasts release

RANKL

how to increase ca levels

- inc osteoblast activity

- reabsorbing more ca from urine

- activating calcitriol

ricketts diease

lack of vit d and calcium in children = inadequate calcification of new bone, abnormal epiphyseal plates, weak bowed limbs

osteomalacia

in adults lack of vit d and calcium can result in abnormal mineralisation of mature bone, weak bones prone to pseudofractures

adrenal glands

pair of endocrine glands above the kindeys the secrete adrenaline and epinepherine to help body in times of stress

adrenal cortex and medulla

adrenal cortex

zona glomerulosa, zine fasciculata and zona reticularis