GMH endocrine

endocrine glands

epithelial tissue derivatives specialised for secreting

what are the four chemical messengers

1. autocrine; local either on neighbouring cells or itself

2. neurotransmitter; short range chemical messengers diffusing across the synapse

3. neurohormones; released into blood by neurosecretory neurons and travel through blood

4. hormones long range messengers secreted into blood by endocrine gland

what are hormones changing

rarely change cellular function; alter rate or normal functioning

what are the two categories of hormones

1. hydophillic=peptide and catecholamines; surface receptors

2. hydrophobic=thyroid and steroid hormones; nuclear receptor

surface versus nuclear receptors

surface receptors=hydrophilic hormones=peptide hormone binds which activates G protein and induced intracellular signals→includes prolactin, ACTH, vasopressin, oxytocin, and insulin

nuclear receptors=hormone binds inducing heat shock protein detachment which uncovers the nuclear localization sequence and then the hormone enters the nucleus acting as a TF

-oestrogen, cortisol, testosterone, aldosterone

primary versus secondary endocrine glands

primary=thyroid, parathyroid, pituitary, adrenal and pineal

secondary=liver and heart

hyposecretion and hypersecretion

primary hypo=within gland abnormality, secondary due to tropic hormone deficiency

primary hyper=too much hormone due to within gland abnormality, secondary do to excessive gland stimulation

two functions of vasopressin

1. binds V2 and promotes H20 reabsorption

2. binds V1 causing arteriole vasoconstriction

noreepinephrine

hormone from adrenal medulla but NT from NS

pituitary gland location veruss hypothalamus

is 1cm and lies at the base of brain below hypothalamus and is connected via nerve fibers and blood vessels

hypothalamus lies at the base of the brain and the pituitary connected to the base of the brain via the infundibular stalk

anterior versus posterior pituitary

anterior=epithelial struture developing from rathkes pouch

posterior=neural structure developing from midbrain floor consisting of nerve fibers running from hypothalamus to anterior pituitary (oxytocin and vasopressin=peptide hormones stored in axonal ends)

how are vasopressin and oxytocin produced

nerve cell bodies in the hypothalamus and then are packaged into vesicular granules and then are transported down axons into posterior lobe and are released from terminal similar to neurotransitters

Vasopressin (ADH)

controls variable water reabsorption in final tubular segments of kidney

65% of water reabsorption is obligatory in the proximal tubule while in the distal tubule and collecting duct it is variable (ADH dependent)

Increases tubule cell permeability to water via aquaporin 2 channel insertion

water deficiit increases ADH and vice versa

ADH binds with receptor sites on basolateral membrane of a principal cell in distal or collecting tubule which activates cyclic AMP increasing H2O permeability by AQP-2 water channel insertion

membrane is impermeable to water in the absence of ADH

oxytocin

bonding hormone→increases during birth as uterus increases receptors; synthetic oxytocin can induce labour

aids in smooth muslce contraction so milk ejection

anterior pituitary

epithelial derived upgrowth from roof of oral cavity; regulated by hypothalamic hormones

unlike posterior pituitary→anterior pituitary itself synthesizes the hormones it releases into the blood

1. somatotropes makes growth hormone

2. thyrotropes secrete TSH

3. corticotropes produce ACTH to stimulatee cortosil section by adrenal gland

4. gonadotropes secrete FSH and LH

5. lactotrophs secrete prolactin

anterior hormone pituitary secretion regulated by

hypothalamic hormones and feedback by target gland hormones

factors influencing growth

growth hormone, genetics, protein in diet, freedom from stress (cortisol can promote protein breakdown, blocking GH secretion

GH, somatomedins (IGFs), estrogen and testoserone, thyroid hormones, calcitonin, PTH and vitamin D

growth hormone release

is not continous→featal growth is promoted by placenta hormones so GH plays no role however first two years of life is the postnatal growth spurt and puberty growth spurt is promoted by teste androgen production and in women androgen from adrenal gland less potently promote growth

prepuberty sex differences in growth are not apparent

testoserone and estrogen affect on height

both act on bone to halt its further growth so full height attained by end of puberty

growth hormone release

from AP in several bursts; high in morning before waking and low at night; stimulation occurs during deep sleep

growth hormone releasing hormone (GHRH) produced by hypothalamic neurons

GHRH receptor is 7 transmembrane domain G-PCR

GH bursts initiated by bursting secretion of GHRH and terminated by somatostatin

GH releases IGF1

acts on bone and soft tissues to promote growth; protein synthesis and lengthening and thickening of bones

GH stimulates liver to produce IGfs which stimulatee bone and soft tissue growth→prevent apoptosis and cause hypertrophy

IGF can overcome GH defects

metabolic effects of growth hormone

increase fatty acid in blood due to fat breakdown and increase blood glucose due to decreased glucose uptake by muscles

pituitary gigantism

GH excess due to AP tumour

somatostatin medication stop GH production

Dwarfism

GH defiency, low GH is treated with GH; hereditary=low GH, Laron Dwarf=defectivee GH receptor and African Pygmy=defective IGF-1 receptor

overall GH metabolic effect

mobilising fat stores as major energy substrate while conserving glucose for glucose dependent tissues such as the brain since it can only use glucose as its metabolic fuel, yet it cannot store glycogen

GH effects only manifest when sufficient TH is present

thyroid gland

located on front upper part of trachea developing from small outgrowth of the tongue

follicular cells arranged in hollow spheres form the functional units; colloid is the substance serving as extracellular storage for TH

three types of thyroid hormone

T3 and T4 in follicates and calcitonin in C cells

T3 and T4 function to accelerate metabolism and increase substrate turnover

tyrosine based hormones meaning T3 as three iodine and is more effective but T4 as four but is more abdundant

how are T3 and T4 levels controlled

by TSH from AP; thyroid hormone is the main determinant of BMR and increases target cell responsivess to catecholamines, increases HR and contraction force

TH negatviy feedback loop with AP production TSH

Goiter

low iodine uptake=no T3 or T4 made, iodide uptake increases and thyroid can grow by 10X

Hashimotos

autoimmune where autoantibodie destroy thyroid follicular cells

hypothyroidism

; primary is failure of thyroid gland itself and secondary is due to a deficit of TRH, TSH or decrease in iodide

generalized fatigue, weight gain, deep voice

hyperthyroidsim

graves disease=autoimmine where TSH is mimicked by antibodies→treated with beta blockers and antithyroid medication

weight loss and bulging eyes

adrenal glands

embedded above each kidney in capsule of fat and each has two division

1. cortex(outer part)=makes steroid hormones, aldosterone, cortisol, androgen sex steroids (DHEA)

2. medulla(inner part)=chromaffin cells from sympathetic NS→catecholamines, epinephrine, and norepinephrine

cortex layers

1. zone glomerulsoa=outermost

2. zona fasciulata=middle and largest

3. zone retiularis=inner most zone

aldosterone

mineral corticoid that maintains electrolyte balance; low Na+ or high K+→RAAS→angiotensin II activated which increases aldosterone relase from adrenals→acts on istal renal tubule to increase Na+ and water retention, and increase K+ and H+ ion excretion

Low Na+ or high K+→angiotensin II→adrenal cortex→aldosterone

cortisol

secreted in diurinal rythym playing a role in stress to increase blood glucose and blood fatty acids, control water and electrolyte balance and is also antiinflammatory and immunosuppressive

negative feedback on hypothalamus(CRH) and anterior pituitary(ACTH)

CRH→ACTH→adrenal cortex→cortisol

Catecholamines

adrenal medulla, stimulated by SNS activation; adrenaline for fight or flight responses

glucocorticoid therapy

adrenal fatigue/failure in addisons disease and is also antiinflammatory to reduce T cell proliferation in asmtha, eczema or cancer as anti emetic

benefits must outweight cost due to cushings symptoms of decrease immune system osteoporosis weight gain

Addisons disease

low corticoids (corticoids and aldostrone)

primary=damaged adrenal glands via autoimmune or TB

secondary=low ACTH

weight loss, low liver glycogen

treated witth steroid replacement therapy

cushings

high glucocorticoids→ACTH secreting tumour in pituirty

obesity, hyperglycemia, moon face

treated with antiglucocorticoids, tumour removal

Conns syndrome

excessive mineralcorticoids (aldosterone)

primary=tumour, secondary=excessive RAAS in kidney disease

water and salt retention, increase ECF and hypertension

HPA axis

generalized stress response=increas epinephrine secretion from adrenal medulla chromaffin cells

increase CRH-ACTH-cortisol (HPA) mobilizing metabolic resources while RAAS and vasopressin maintain blood volume and pressure

chronic stress causes heart disease, hypertension, depression with prolonged CRH release

long versus short cortisol loop

long=cortisol acts on CRH neurons in hypothalamus to stop CRH

short=cortisol acts on AP cells to stop ACTH release

Islets of Langerhans

beta cell secretes insuline and alpha cell secretees glucagon while D-cells secrete somatostain (glycogen breakdown)

insulin is synthesized as a prohormone then cleaved to a mature peptide

excitation secretion coupling stimulates insulin exocytosis

food intake

increases PSNS activation and beta cells release insulin

diabetes mellitus=most common endocrine disorder

T1D childhood onset loss of beta cell function

TIID=slow development and is remedied through lifestyle changes

spurs excessive eating due to cells being starved from carbohydrates and dehydration as blood glucose increases due to ketoacidosiis and brain O2 decreases

calcium

1 kg of Calcium in human body with 99% in skeleton and teeth

.9% intracellular in soft tissue and .1% in extracellular fluid; half of ECF Ca is bound to plasma proteins or complexed with PO4³- so it is not available for cellular reactions whereas the other half can pass from plasma to ICF and interact with cells

free ECF Ca2+

only this is biologically active and subject to regulation; functions to prevent aberrant neuromuscular exciteability

fall in this causes overexcitability and rise in depression

excitation contraction coupling versus stimulation secertion coupling

cardiac and smooth muscle results from increased Ca2+ permeability in response to AP

stimulation secretion coupling in B-cells→Ca2+ entry=>insulin

bone remodeling

skeleton acts as storage depot for Ca2+ and is turned over every ten years

1. osteoblasts=build bone via seceretion of extracellular organic matrix within which calcium and phopshate crystals precipiate

2. osteocytes=retired osteoblasts imporsioned with in bony call desposited around them

3. osteoclasts=breakdown matrix and reabsorb bone in presence of PTH to increase Ca2+ levels in plasma

signals that osteoblasts produce

1. RANK ligand=osteoclast.mascrophage→differentiate to osteoclasts and prevent apoptosis→increas osteoclast action and when this is more than osteoblast→decrease bone mass

2. osteoprotegrin (OpG)=binds to rank ligan so it cant bind→decreases osteoclast action→osteoblast outpaces clast and there is an increase in bone mass

bone deposition

mechanical stress favours bone deposition; in children bone builders outpact destroyers (IGF1 and GH); atheletes have greater stress on bone so mass increases

bone density peaks at 30 and declines at ago 40

osteoporosis

reduced osteablast activity and an increase in osteoclast acitvity; post menoppausal women

what three hormones control plasa concetrations of Ca2+ and phopshate

1. calcitonin (thyroid gland C-Cells)

2. parathyroid hormone

3. vitamin D

what regulates calcium

hormonal control between ECF and bone (short term), kidneys(seceretion), and intestines (absorption)→Ca2+ is involved in the function of all cells

Parathyroid hormone

=small oval gland assoicated witht he thyroid and PTH is a major adjustor whereas calcitonin is for fine adjusments.

Principal chief cells secrete PTH in repsonse to low blood Ca2+ leading to an increase in calcium via increase bone calcium release promoting tubular reabsopration and increase absorption from the small intestine via vit D activiation

PTH 2 major effects on bone

uses bone as a bank to maintain Ca2+ plasma levels with two major effects on bone.

1. induces fast Ca2+ influx into plasma from small labile pool of Ca2+ in bone fluid

2. stimulates bone dissoultion promoting transfer into plasma of Ca2+ and phosphate from stable bone mineral pool within the bone

osteocytic-osteoblastic bone membrane

entombed osteocytes and surface osteoblasts are interconnected via long cytoplasmic processes extending from these cells and connect to one another within caniculli

seperates mineralized bone from plasma in central canal

bone fluid lies between the membrane and mineralized bone

calcitonin

comes from C cells of thyroid gland and respond to high plasma Ca2+; PTH antagonist lowering plasma calcium and phosphate via inhibiting osteoclast activity and stimulates calcium secretion in kidneys

vitamin D

cholesterol derivative when exposed to the sun and is activated by the liver then the kidneys

essential for GI calcium and phopshate absorption, increases renal calcium reapsorption and reugulates osteoclast and blast activity; kidney enzymes are stimulated by PTH in response to fall in calcium plasma levels

calcium metabolism disorders

1. PTH hypersecretion(hyperparathyroidism)= hypersecreting tumour in PTH gland→hypercalcemia and hypophospahtemia-reduced nerve excitiably and muscle weaknesss-excessive calcium and phopshate from skeletal stores leads to bone thinning and an increase in kidney stones

2. PTH hypsecretion (hypoparathyroidism)→autoimmine attack or removal during thyroid removal surgery-hypocalcemia and hyperphosphatemia

3. vitamin D deficiency=impaired intestinal absoprtion of Ca2+ and PTH maintains plasma calcium levels at thee expense of bone