21673 – Adrenaline
1: stimulates glycogenolysis in liver and muscle
2: mobilises free fatty acids from adipocytes
3: increases the B.M.R. (Basal Metabolic Rate)
4: increases the pulse pressure
1: T - B2 receptors stimulate hepatic and muscle glycogenolysis
2: T - B1 and B3 receptors increase lipolysis to free FFAs for gluconeogenesis
3: T - increases metabolic rate to increase energy production in flight or fight mode
4: T - increases the HR and CO (B1 receptors) but causes vasodilation in peripheral tissues (B2) so decreases total peripheral resistance. Thus widens pulse pressure
How does ADRENALINE
Adrenaline:
- Increases HR and CO by B1 receptors
- Causes peripheral vasodilation so decreases TPR by B2
- Similar increase in blood pressure but not sufficient enough to override the direct cardioaccelatory effect of adrenaline on the B1 receptors
- WIDENS pulse pressure
How does NORADRENALINE affect HR, CO, TPR, SBP and DBP?
Noradrenaline:
- TPR increases because of noradrenaline effects on A1 receptors in most peripheral tissues
- SBP and DBP rise
- This hypertension causes reflex bradycardia mediated by the carotid and aortic baroreceptors
- This bradycardia overrides the stimulatory effect of noradrenaline on the B1 adrenergic receptors
- Therefore HR and CO DECREASE with noradrenaline infusion
How does adrenaline / noradrenaline affect blood glucose?
- Both stimulate glycogenolysis (B2) receptors via cAMP upregulation
- Stimulation of B2 also causes pancreatic islet cell secretion of insulin and glucagon
- Stimulation of A1 causes inhibition of this secretion
How does adrenaline / noradrenaline affect blood potassium?
- Both cause initial increase likely due to B2 mediated hepatic release
- Then a prolonged decrease in K+ via a B2 mediated entry in to cells
- A1 receptors may oppose this effect
Which of the foillowing are induced by noradrenaline?1: 1: reduction of the cardiac output
2: constriction of skeletal muscle arterioles
3: stimulation of hydrolysis of fat to release fatty acids and glycerol
4: stimulation of the secretion of gastric parietal cell HCl.
1: T - increases SBP and DBP by causing A1 mediated vasoconstriction in peripheries thereby increasing TPR. Reflex bradycardia from aortic/carotid baroreceptors
2: T - A1 mediated vasoconstriction
3: T - B2 mediated hepatic and muscular lipolysis
4: F - Ach stimulates parietal cell secretion of HCl
What are the effects of dopamine on the circulatory system?
- Renal vasodilatation
- Mesenteric vasiodilatation
- Positive inotrope via B1
- ## Increases SBP
What is the effect of dopamine on the secretion of prolactin?
Prolactin in secreted from the anterior pituitary gland. Its secretion in inhibited by dopamine. Drugs that inhibit the secretion of dopamine can therefore cause an excess of prolactin secretion such as lots of the anti-psychotics, which result in hyperprolactinaemia.
What is the role of glucocorticoids on the catecholamines?
Small amounts of glucocorticoids are required for the catechols to act on vessels so they are essential in the smooth muscle response.
What is growth hormone?
- Released in the anterior pituitary, one of 6 hormones
- UPREGULATED by growth hormone releasing hormone
- DOWNREGULATED by somatostatin
What STIMULATES growth hormone secretion?
- Increased in situation of starving state or increased fuel requirement or threatened need for increased fuel requirement
- Hypoglycaemia, stress, exercise, starvation, deep sleep
- L-dopa (dopamine and other catecholamines) presumably as part of the stress pathway
- Oestrogens and androgens (hence growth spurt in puberty!)
What DECREASES growth hormone secretion?
- Cortisol
- Free fatty acids
- High glucose
- REM sleep
- Negative feedback via circulating growth hormone and insulin-like growth factor 1
What are the DIRECT effects of growth hormone on the body?
DIRECT effects: (wants to increase extracellular fuel stores (FFAs, glucose)
- Adipolysis to free up fatty acids to add to the fuel pool
- Increase hepatic glucose output
- Increase protein synthesis
- Increase mitosis (hence GROWTH)
- Increase erythropoesis
- Decreases glucose uptake and use by cells, which thus reduces insulin sensitivity and can predispose diabetes
- Increases sodium retention
- Increases circulating phosphate and calcium by increases GIT resorption of calcium and renal resorption of phosphates
What are the INDIRECT effects of growth hormone on the body?
In summary indirect effects are those enacted by hepatic insulin-like growth factor 1 which is stimulated by GH release. IGF-1 has similar hormonal function to insulin:
- Increase cellular glucose uptake and utilisation
- Decreases lipolysis
- Increases protein synthesis
- Increase epiphyseal growth
IGF-1 is stimulated to be released from the liver by:
- GH
- Tetraiodothyronine (T4)
- Increases glucose utilisation
- Androgens (hence growth spurt inpuberty)
IGF-1 release is decreased by:
- High serum cortisol
- Starvation
- Insulin deficiency
- High oestrogens
What is prolactin?
- One of the hormones secreted by the lacotrophs of the anterior pituitary gland, similar in structure to growth hormone.
- Dopamine = prolactin hormone inhibiting hormone.
ACTIONS:
1 Prolactin promotes milk SECRETION in the breast with both oestrogen and progesterone.
- It does not, however, cause the milk ducts to eject the milk, just to produce it, (OXCYTOCIN causes ejection)
- Prolactin also acts in opposition to gonadotropes (LH and FSH) so high levels decrease the actions of LH and FSH on the gonads. Excessive prolactin in both males and females can result in infertility as in the case of prolactinomas.
What INCREASES prolactin secretion?
- Nipple stimulation in non-lactating women
- Stressors such as surgery, psychological, hypoglycaemia and exercise
- Pregnancy, particular in the third trimester
- Dopamine blockers (because dopamine is prolactin hormone inhibiting hormone
- Thyrotropin releasing hormone
- Thirst and vasopressin (ADH)
- Oestrogens
What DECREASES prolactin secretion?
- Dopamine (L-dopa)
- Bromocryptine (dopamine agonist)
- Apomorphine!?
What are the main clinical features of hyperprolactinaemia?
- Secondary amenorrhoea (by suppression of gonadotrophs LH and FSH
- Galactorrhoea
- Hypogonadism can lead to osteoporosis and impotence
What is follicle stimulating hormone?
FSH released from the anterior pituitary gland to stimulate both male and female gonads.
Female:
- Causes maturation of primordial follicles
- Acts on the theca interna and externa
- Just prior to ovulation there is a sharp increase in FSH released
Male
- Increases the seminiferous tubules in the testes to produce sperm
- Increases the maturation of spermatids to spermatozoa via Sertoli cells
- Increases the production of inhibin which causes a decrease in FSH production
What is luteinising hormone?
LH is released from the anterior pituitary gland in close association with FSH to act on both female and male gonads,
Female:
- Leuteinising hormone low in the follicular phase of the menstrual cycle as it is inhibited by the gradually increasing amount of oestrogen.
- When the oestrogen concentration reaches a critical point, it upregulates the production of LH and thus is responsible for the spike in LH seen just before ovulation
- LH causes ovulation
- LH acts on the theca interna cells to luteinise the ovarian follicle following ovulation
- This enhances the production of progesterone and oestrogen
Male:
- Acts on the interstitial fatty Leydig cells to cause growth and androgen production
What is vasopressin?
One of two hormones produced int he posterior pituitary gland in the paraventricular and supraoptic nuclei. Also known as antidiuretic hormone. ADH comes from neurophysin II neurones as opposed to oxytocin which comes from neurophysin I.
What increases ADH secretion?
Triggers:
- High blood osmolality (concentrated blood)
- Low blood volume
- Low pressure
Others:
- Stress
- Morphine
- Post-op
- Angiotensin II
What is the pineal gland?
An endocrine organ in close proximity to the brain like the anterior pituitary gland. It has its own fenestrated capillaries like the pituitary and thus is not bounded by the blood brain barrier.
Primarily functions to secrete melatonin which is the regulatory hormone for human circadian rhythm. Similar structure to serotonin, it is derived from tryptophan via serotonin.
Peak secretion at night time which drops off as dawn approaches.
Innervation :
- Retinohypothalamic fibres to the suprachiasmatic nucleus of the hypothalamus
- Hypothalamus to the superior cervical ganglion with descending pre-ganglionic neurons
- Ascending post-ganglionic neurons innervate the gland itself and release noradrenaline to regulate melatonin release
No impact on potassium metabolism, it acts via a cAMP pathway.
Where is serotonin found in the body?
Highest concentration in platelets and the GIT (in enterochromaffin cells and the myenteric plexus).
It is also found centrally in the brainstem and midline nuclei.
