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Endocrine System (Hormones & actions (Stressor
Any stimulus that…
Endocrine System
Hormones & actions
Hormone
- First identified Secretin
- Secreted by specialist cells, grouped together to form a ductless organ
- Amount secreted depends on original stimulus
- Blood concentration is always low to be secreted
- Once in blood, hormone circulates to distantly located target cell where it interacts with specific receptors to elicit specific effects involving the regulation of cellular activities
Types of endocrine hormonesAutocrine
- Acts on cell that produces the hormone
Paracrine
- Affect neighbouring cells
Peptides (proteins & polypeptides)
- Synthesised by the same process as other proteins
- Stored intracellularly in small amounts
- Hydrophilic so carried in blood plasma
- Receptors found embedded in cell membrane with hormone binding site facing outwards
Steroids
- Not stored
- Synthesised and released as required
- Hydrophobic so carried bound to specific plasma binding proteins
- Cells that synthesise steroid hormones contain fat droplets (mainly cholesterol esters)
- Receptors are intracellular, usually within the nucleus
Factors which affect: The responsiveness of a tissue
- Number of functional target cells
- Number of receptors
- Availability of intracellular components of the hormone for hormone manufacture
- Presence of a non-competitive antagonist of the hormone
The sensitivity of a tissue
- Receptor number
- Intracellular components
- Rate of hormone degradation
- Presence of competitive antagonist
Hormone controlDirect stimulation
- Immediate response to a nervous stimulation
- Nerve endings secrete neurohormones
Direct negative feedback
- Interaction between controlling the hormone and the metabolite e.g PTH release and calcitonin, raised blood plasma inhibits calcitonin release
Indirect negative feedback
- Some peripheral endocrine glands regulated by hormones released from by the anterior pituitary
Positive feedback
- The hormone stimulates its own production, controls ovulation
Rhythms
- A characteristic pattern over time, monthly cycle and cortisol circadian rhythm
Stressor
- Any stimulus that causes a stress response
- Can be physical or psychological
- The body's homeostatic mechanisms respond to return internal environment back to normal ranges and counteract stress
Stress responseOccurs in 3 stages:
- Fight or flight
- Resistance reaction
- Exhaustion
Fight or flight
- Nerve impulses from hypothalamus
- Impulses go to the sympathetic nerves of the autonomic system and adrenal medulla
- Increases glucose and oxygen to the muscles
Effects
- Increased heart rate and force of beat
- Constriction of blood vessels in viscera and skin
- Dilation of blood vessels to heart, lungs, brain and skeletal muscles
- Contraction of spleen
- Conversion of glycogen to glucose
- Sweating
- Dilation of airways
- Decreases digestive activities
- Water retention, raised blood pressure
Resistance reactionPituitary increases production of:
- Adrenocorticotrophin hormone (ACTH)
- Human growth hormone (stimulates lipolysis and glycogenolysis)
- Thyroid stimulating hormone (increases utilisation of glucose to produce ATP via T3 & T4
At the same time coping mechanisms are initiated
Exhaustion
Happens when the body becomes so depleted of resources that the resistance stage cannot be sustained
Consequences of high levels of cortisol
- Muscle wasting
- Suppression of the immune system
- Ulceration of the GI tract
- Failure of pancreatic beta cells
Thyroid
- Weighs 10-20g
- Rich blood supply
- Rich lymphatic supply
- Thyroid secreting cells are within thyroid follicles
- In each thyroid follicle epithelial, cells surround a lumen filled with thyroglobulin
- Iodine combines with tyrosine attached to thyroglobulin in the thyroid follicles to begin hormone formation
ThyroglobulinAn iodinated glycoprotein which is the precursor for T3 (tri-iodothyronine & T4 (thyroxine)
- There is sufficient for 100 days secretion
- Uptake of colloid from the lumen is related directly to the level of stimulation of the gland by TSH secreted by the pituitary
Thyroid hormone transportThere are three hormone binding proteins, all synthesised by the liver
- Thyronine binding globulin
- Albumin
- Thyroxine binding pre-albumin
On entering the target cells, thyroid hormones bind to proteins and are then slowly released
Thyroid hormone effectsMost cells require thyroid hormone for normal function, but 2 main functions are
:
1. Increase overall metabolic rate
- Stimulate O2 consumption
- Stimulate heat production
- Increase O2 delivery to tissues by increased ventilation, cardiac output and red cell mass
- Increases intestinal absorption of glucose
- Increases metabolism of glycogen, fat and protein (catabolic)
- Stimulate growth and repair in children
Growth & development
- Essential for differentiation and maturation of tissues in foetus, newborn and child
- uncorrected deficiencies result in cretinism, neonatal screening undertaken to prevent permanent mental retardation
- Hormone acts indirectly at the anterior pituitary gland to stimulate synthesis and secretion of growth hormone, necessary for skeletal growth and bone maturation
Under-active thyroid
- Goitre and course thinning hair
Over-active thyroid
Calcitonin (thyrocalcitonin)
- Produced by the parafollicular C cells
- Secreted in response to raised ionised plasma calcium
- Inhibits osteolysis and bone resorption
- Causes increased urinary excretion of calcium and phosphate
Parathyroid hormone
- 4 parathyroid glands attached to the thyroid gland
- PTH is a polypeptide
- Released in response to lowered calcium plasma levels
- Restores calcium in the plasma and increase phosphate concentration
Actions of PTH
- Kidney - Stimulates reabsorption of calcium, inhibits reabsorption of phosphate and stimulates production of enzyme to convert vitamin D to active form
- Stimulates production of active vitamin D in the GI tract
- In bone stimulates osteolysis and resorption of calcium
Pancreas
- 12.5 - 15cm in length
- Located in the curve of the duodenum
- Mixed gland - 98% exocrine tissue, remaining tissue islets of langerhans
Islets of langerhans secret:
- Glucagon from A cells
- Insulin from B cells
- Somatostatin from delta D cells
- Pancreatic polypeptide hormone from F cells
All cell types contain granules that release their hormones into the capillaries
Insulin
- Polypeptide B cells store about 10x daily requirements
- Release from storage granules is calcium dependant
- Basal and stimulated release
- Primarily controlled by blood glucose levels
- Insulin has a half-life of 10-15 mins in circulation and degraded by liver and kidneys
Other stimulants of insulin release
- Amino acids e.g leucine
- Fatty acids
- Growth hormone, thyroxine and glucocorticoids are necessary for normal islets development
- Gut hormones stimulate insulin release directly or by potentiating the glucose response
Hypoglycaemic effect
- Lowers blood glucose, also regulates energy metabolism
- Tries to maintain the blood glucose at 4-8mmol/l
- All cells require glucose as energy source, but not all cells require insulin for transport of glucose into the cell
- When insulin is absent, the cells that require it change to use free fatty acids as an energy substrate, resulting in metabolic acidosis. Emergency admission with ketoacidosis may be the first time type 1 diabetes is diagnosed
Other effects
- Increased protein synthesis
- Decreased lipolysis
- Increased lipogenesis
Insulin deficiencyType 1 diabetes
- Insulin dependant auto-immune destruction of B cells
Type 2 diabetes
- Not insulin dependant, insulin secretion severely depressed
Insulin excess
- Hypoglycaemia
- Confusion, lethargy, tiredness, blurred vision, difficulty speaking
- Increased sympathetic activity such as sweating, anxiety and tachycardia (heart rate that exceeds normal resting heat rate)
Stages
- High blood glucose (hyperglycaemia)
- Beta cells secrete insulin
- Insulin:
- Accelerates diffusion of glucose into cells
- Speeds conversion of glucose into glycogen (glyconeogenesis)
- Increases uptake of amino acids and increase protein synthesis
- Blood glucose return to normal
- If blood glucose continues to fall, hypoglycaemia inhibits insulin release
Glucagon
- Secreted by alpha cells
- Released from storage granules stimulated by hypoglycaemia
- Also stimulated by a lesser extent by CCK
- Release inhibited by insulin and pancreatic somatostatin
- Stimulation of autonomic nervous system also stimulates the release
- Half-life of 5-6 mins, degraded by liver and kidneys
Actions of glucagonElevates blood sugar by:
- Acting on the liver to stimulate glycolysis and gluconeogenesis and inhibiting glycogenesis
- Acts on adipose tissue to stimulated lipolysis. The glycerol produced by lipolysis is used by the liver for gluconeogenesis and the fatty acids as an energy source by some tissues
Stages
- Low blood sugar (hypoglycaemia)
- Alpha cells secrete glucagon
- Glucagon acts on liver cells to convert glycogen to glucose, and form glucose from lactic acid and certain amino acids (gluconeogenesis)
- Blood glucose returns to normal
- If blood glucose continues to rise, it inhibits the release of glucagon
Somatostatin
- Also secreted by anterior pituitary and other GI sites
- Has inhibitory effect
- Release by pancreas stimulated by increased glucose, some amino acids, secretin, CCK
Pancreatic polypeptide
- Secreted in response to parasympathetic and CCK stimulation of F cells, also presence of protein digestion products in the intestine
- Actions inhibit gall bladder contraction and pancreatic enzyme secretion
Pituitary
Anterior pituitary
Releases hormones in response to hypothalamic hormones
- Adrenocorticotrophin (ACTH) increases glucocorticoids (adrenal cortex)
- Thyroid stimulating hormone (TSH) increases thyroid hormone
- Follicle stimulating hormone (FSH)
- Luteinising hormone (LH) increases hormone production in gonads
- Prolactin increases lactation when breast feeding
- Human growth hormone increases cell division and growth
Posterior pituitary glandAdapted axons of neurons store and secrete hormones at their termini in the pituitary gland (but the cell bodies and dendrites originate in the hypothalamus
- Oxytocin increases milk ejection and uterine contraction
- Antidiuretic hormone (ADH) increases water reabsorption in the kidneys, restriction of arterioles
Adrenal glands
- Outer cortex 80-90% of the weight
- Total weight 8-10g
- Whole gland enclosed in a capsule with rich blood supply
Adrenal cortex hormones
Glucocorticoids - cortisol
Mineralocorticoids - Aldosterone
Adrenal androgens (Sex steroids) - testosterone
MineralocorticoidsAldosterone
- Prevents excessive loss of extracellular fluid
- Aids conversion of sodium, excretion of potassium and water retention
- Aldosterone secretion is stimulated by angiotensin II
GlucocorticoidsCortisol
- Determines the responsiveness of most tissue to other stimuli
- Raises plasma glucose concentration
- Prevents excessive water retention
- Prevents inappropriate inflammatory and immune responses
- Secretion stimulated by ACTR (adrenocorticotrophin)
- Cortisol secretion follows a circadian basal rhythm which is increased by many stressors
- There is a coordinated activation of adrenaline and cortisol secretion in response to acute stress
Adrenal Medulla Hormones:
- Epinephrine
- Norepinephrine
- Consists of chromaffin cells which secrete the catecholamines - noradrenaline and adrenaline in response to stimulation of sympathetic neurons
- Stressors that increase adrenaline levels are hypoglycaemia, heavy exercise and surgery
- High level of cortisol also stimulates catecholamine release
Catecholamines
- Catecholamines are noradrenaline and adrenaline
- Secreted by chromaffin cells in the adrenal medulla
- Short half life
- Metabolites excreted in urine
- They act on beta and alpha adrenoreceptors to facilitate increased substrate and oxygen delivery to active tissue
- Increased: heart rate, blood pressure, lipolysis, glycogenolysis and sweating
- Selective vasoconstriction and vasodilation
- Bronchodilation
- Decreased gut motility
Structure & function
Structure of the endocrine system
Hypothalamus
Anterior pituitary
Posterior pituitary
Thyroid gland
Parathyroid gland
Adrenal cortex
Islets of langerhans
Testes
Ovaries
Hypothalamus
Neural stimulation causes secretion of releasing or inhibitory hormones that act on anterior pituitary:
- Corticotrophin releasing hormone (CRH) leads to increased adrenocorticotrophin hormone (ACTH) influences production and secretion of adrenal cortex hormones
- Thyrotrophin releasing hormone (TRH) leads to increased thyroid stimulating hormone (TSH), stimulates secretion of T3 and T4
- Gonadotrophin releasing hormone leads to increased LH & FSH, stimulates ovulation
- Prolactin inhibiting hormone leads to decreased prolactin, peptide hormone associated with lactation, breastfeeding. Suckling on nipples stimulates production (lactogenesis)
- Prolactin releasing hormone leads to increased prolactin
- Growth hormone releasing hormone leads to increased growth hormone
Nervous system & endocrine system interaction
- Both extracellular communications systems
- Nerves are capable of synthesising and secreting molecules into the blood that act as circulating hormones
neural and endocrine responseResponse to haemorrhage
- Blood loss causes nerve stimulation causing compensatory changes in the circulatory system
- ADH hormone is released which causes increased water absorption by the kidneys and secretion of hormones from the adrenal cortex and medulla
Milk ejection reflex
- Suckling baby
- Via spinal cord, oxytocin produced by neuroendocrine cells in the posterior pituitary
- Reflex abolished by anaesthesia