(PM3B) Endocrine Systems Flashcards
What does the endocrine system and NS regulate?
(1) Growth
(2) Reproduction
(3) Development
(4) Senescence - age deterioration
What are the three classes of hormones?
What can be said for their hydrophilicity?
(1) Proteins/ peptides - all hydrophilic
(2) Cholesterol derivatives - all hydrophobic
(3) Modified amino acids - hydrophilic (adrenaline) or hydrophobic (thyroid hormones)
What factors affect circulating hormone level?
(1) Rate of secretion - endocrine gland
(2) Rate of metabolism - target tissue/ kidney/ liver/ blood
(3) Serum binding protein availability
What type of hormones must be injected? Why? State an example.
Protein hormones
They are digested in the stomach
Growth hormone
What is an ectopic hormone-secreting tumour?
A tumour not in an endocrine gland which is producing hormones
What is a tumour that produces hormones in a place that does not normally produce hormones called?
Ectopic hormone-secreting tumour
What is the most common immunological cause of hyper secretion in the thyroid?
Graves’ disease
Which dysfunction is a reason for a hormone having no effect on a usually targeted tissue?
End organ sensitivity/ resistance to hormone
What are the 2 types of organ sensitivity defect called?
(1) Genetic defect
- e.g. Laron syndrome
- Increases production of non-functioning growth hormone
(2) Acquired defect
- e.g. Type 2 DM
- Impaired insulin receptor signalling with normal levels of insulin
What is a pituitary adenoma?
Growth of a functional tumour inside the endocrine gland
Often benign
(1) What hormone does the parathyroid secrete?
(2) What does this hormone affect?
(1) Parathyroid hormone
(2) Controls calcium levels
What are the 3 types of endogenous rhythm?
What do they mean?
Give an example.
(1) Ultradian - cycles in minutes - GnRH (hormone) pulses
(2) Circadian - cycles in days - testosterone/ cortisol
(3) Infradian - cycles in months - LH - 28 day cycle
What is an ultradian rhythm?
Cycles in minutes
What is a circadian rhythm?
Cycles in days
What is an infradian rhythm?
Cycles in months
What type of feedback mechanism is most common?
Negative feedback
What is an example of a closed loop mechanism?
Negative feedback in homeostasis
What is an example of a positive feedback loop?
Milk-ejection reflex - caused by oxytocin
Pre-ovulatory LH surge - caused by oestrogen
What changes in the EXTERNAL environment can the hypothalamic-pituitary system respond to?
(1) Photoperiod - day/ night cycle
(2) Temperature
(3) Food availability
(4) Mate availability
(5) Stress
What changes in the INTERNAL environment can the hypothalamic-pituitary system respond to?
(1) Target organ feedback signals
(2) Nutritional status
(3) Water/ salt balance
(4) BP/ HR
(5) Pregnancy
(6) Trauma/ disease
What is the bone cavity that the pituitary gland sits in called?
Sella turcica
What is the composition of the pituitary gland?
Two lobes
(1) Anterior pituitary
(2) Posterior pituitary
What is a parvocellular peptidergic neurone?
A neurone that controls hormone secretion from anterior pituitary - e.g. TSH
What is a magnocellular peptidergic neurone?
A neurone that controls hormone secretion from posterior pituitary - e.g. oxytocin/ vasopressin - ADH
How is the anterior pituitary communicated to?
Via the hypophyseal portal system
How is the posterior pituitary communicated to?
Via a direct neural connection
What is the blood supply of the anterior pituitary called?
Superior hypophyseal artery
What is the blood supply of the posterior pituitary called?
Inferior hypophyseal artery
How does the posterior pituitary release hormones?
Directly from axon terminals into capillaries
How many types of parvocellular hypothalamic neurones are there?
5
What is another name for a neuropeptide?
A hypothalamic hormone
What is another name for a hypothalamic hormone? Give an example.
Neuropeptide
TRH
Where do parvocellular hypothalamic neurones terminate?
Median Eminence
Close proximity to primary capillary plexus of hypophyseal portal system.
Define ‘plexus’.
An intricate network of vessels/ nerves
e.g. capillaries
How are hypothalamic hormones (neuropeptides) released?
In a pulsatile manner
What is the effect of most neurones on the anterior pituitary?
Stimulatory effect
What effect to the testes have on the release of GnRH and LH?
Negative feedback
Which hormone decreases release of FSH?
Inhibin
What is the action of inhibin?
Decreases the production of FSH
Where is GnRH produced?
Hypothalamus
What is GnRH?
Gonadotropin-releasing hormone
What are the effects of GnRH?
Stimulates the release of FSH and LH from the anterior pituitary gland
Where are LH and FSH released from?
Anterior pituitary
What is the function of FSH?
Ovary stimulation in ovulation
What is the function of LH?
(1) Ovary stimulation
(2) Stimulates the corpus luteum
- Controls secretion of progesterone, oestrogen and inhibin
What is the function of GHRH?
Stimulates production of GH
What is the function of somatostatin?
Inhibits the production of GH
Where is GH produced?
Somatotroph cells in anterior pituitary
What is the effect of GH?
(1) Promotes growth of bones and muscles
(2) Metabolic effects in most muscles
What are some direct effects of GH on target tissues?
(1) Antagonistic to insulin
(2) Reduces glucose transport into cells
(3) Increases lipolysis
(4) Increased amino acid transport into muscles
- Increases muscle growth
What are IGFs?
Insulin-like mediated growth factors
What is another name for IGFs?
Somatomedins
What is a somatomedin?
An IGF
What is the function of IGFs/ somatomedins?
(1) To mediate the indirect effects of GH
(2) Promote linear growth of bones
(1) What is the effect of GH on IGF production?
(2) Where are IGFs produced?
(1) GH promotes IGF production
(2) Produced in the liver
How does IGF promote the linear growth of bones?
Stimulates cartilage growth plates
What is an example of an indirect effect of GH?
Growth and cell proliferation (division) of soft tissues and viscera (internal organs)
What causes disorders of GH action?
Issues with the GH receptor
How does GH stimulate an effect?
(1) Binds to GH receptor in target tissue
(2) Activates an intracellular tyrosine-kinase cascade
What is Laron syndrome?
A mutation in the GH receptor
What syndrome is associated with GH receptor mutation?
Laron syndrome
How is Laron syndrome detected?
(1) Serum GH above normal
(2) IGF-1 is undetectable - very low
What is the treatment for Laron syndrome?
IGF-1
What are two types of GH secretion disorder? What is their effect and why?
(1) Hypopituitarism
- Decreased GH in childhood
- Leads to dwarfism
(2) GH-secreting pituitary tumour
- Increased GH in child/ adulthood
- Leads to giantism in children
- Leads to acromegaly in adults (coarsened features + thickening of bones & soft tissues)
What is the treatment of dwarfism?
(1) Replacement therapy with human GH - somatotropin
(2) Somatotropin via injection
What is somatotropin?
Human GH
What is human GH called?
Somatotropin
What is the treatment for giantism?
(1) Surgical removal of pituitary gland
(2) Suppression of GH using somatostatin analogues
Give 2 examples of somatostatin analogues.
(1) Lanreotide
(2) Ocreotide
What is the treatment for acromegaly?
(1) Surgical removal of pituitary gland
(2) Suppression of GH using somatostatin analogues
(3) GH receptor antagonist
Give an example of a GH receptor antagonist.
Pegvisomant
What is the H-P-Thyroid Axis?
The hypothalamus-pituitary-thyroid axis cascade which regulates the release of thyroid hormone
What hormone does the hypothalamus produce?
TRH - Thyrotropin-releasing hormone
Where is TRH produced?
Hypothalamus
What are the effects of TRH?
Stimulation of the anterior pituitary to produce TSH
Where is TSH produced?
Anterior pituitary
What is the effect of TSH?
Stimulates the thyroid to produce T3 and T4
What are the effects of thyroid hormone (T3 + T4)?
(1) Increase BMR
(2) Increase HR and force of contraction
(3) Increase activity of sympathetic NS
(4) Enhance sensitivity to catecholamines
(5) Promote growth + maturation
What is Addison’s disease?
Loss of adrenal function
Can be autoimmune
What disease is associated with the loss of adrenal function?
Addison’s disease
What are the symptoms of Addison’s disease?
(1) Fatigue and weakness
(2) Anorexia/ vomiting - can be confused with anorexia nervosa
(3) No sodium reabsorption in distal tubule of kidneys
(4) Hyperpigmentation of patients - especially in skin creases
What hormones does the adrenal medulla produce?
(1) Adrenaline
(2) Noradrenaline
What are the effects of adrenaline/ noradrenaline?
Increased HR in response to exercise/ stress
What two stimuli can increase HR in the presence of a hormone released by the adrenal medulla?
(1) Stress
(2) Exercise
What hormones are produced in the adrenal medulla?
(1) Cortisol
(2) Aldosterone
What is the function of cortisol?
For adaptation to stress
- Mobilises glucose
- Has anti-inflammatory actions at high levels
What is the function of aldosterone?
Maintains the balance of sodium/ potassium in the blood
What are the effects of cortisol?
(1) Modulates carbohydrate, protein, and lipid metabolism
(2) Opposes effect of insulin
(3) Increases plasma glucose levels
- Stimulates gluconeogenesis in the liver
- Promotes storage of glucose
- Decreases glucose utilisation in other tissues
- Used to increase production of glycogen
(4) Stimulates appetite
(5) Increases central obesity in Cushing’s syndrome
(6) Anti-inflammatory
- Decreases number of circulating lymphocytes
- Decreased antibody production
- Impaired cellular immunity
(7) Negative feedback loop on the production of cortisol in the adrenal cortex
(1) What syndrome is associated with the over-production of cortisol?
(2) What causes this?
(1) Cushing’s syndrome
(2)
- Usually a benign tumour of the pituitary/ extreme side effect of steroid medication
- Adrenal tumour (less likely)
What are the symptoms of Cushing’s syndrome?
(1) Central obesity
(2) Skin thinning
(3) Bruising - capillary fragility
(4) HTN
(5) Bone + muscle degeneration
(1) How is Cushing’s syndrome diagnosed?
(2) What are the results that confirm a diagnosis for each cause?
(1) Measurement of [cortisol]/ [ACTH] in blood plasma and urine
(2)
Normal-Very low [ACTH] = ACTH independent –> Adrenal tumour
Moderately-high [ACTH] = Pituitary tumour
High [ACTH] = Ectopic ACTH-producing tumour
What is the function of ACTH?
To regulate the release/ production of cortisol in the adrenal cortex
(1) What is the ‘Dexamethasone Suppression Test’?
(2) What do the results indicate?
(1) A quantitative test to determine the presence of Cushing’s syndrome
(2)
Low-dose dexamethasone = ACTH suppression in healthy patients
Low-dose dexamethasone = No ACTH suppression in patients with Cushing’s syndrome
In a dexamethasone suppression test where is the blood be tested for [ACTH] taken from?
Inferior petrosal sinus
(Where the pituitary gland blood drains)
In a dexamethasone suppression test, [ACTH] can be determined from blood in the inferior petrosal sinus. What is an alternative method of obtaining [ACTH]?
Use of a catheter
What is the treatment for Cushing’s syndrome?
(1) Reduction in steroid medication
(2) Surgical removal of the tumour
(3) Adrenalectomy
What is another name for ADH?
Vasopressin
What is another name for vasopressin?
ADH
What is ADH?
Anti-diuretic hormone
Where is vasopressin (ADH) produced?
Posterior pituitary gland
What is the function of vasopressin (ADH)?
(1) To reduce water secretion by kidney
(2) Vasoconstrictor
Describe the half-life of vasopressin (ADH).
Short
About 5 minutes
Where is vasopressin (ADH) cleared?
Mainly cleared in the kidney
What is the main physiological stimulus of vasopressin (ADH)?
Increased osmotic pressure of the blood
What are other stimuli for the production of vasopressin (ADH)?
(1) Fall in blood volume of >8%
(2) Reduced arterial pO2
(3) Raised arterial pCO2
(4) Raised temperature
(5) Pain/ trauma/ infection
How is a fall in blood volume detected by the body?
Baroreceptors
What is the main action of vasopressin (ADH) at normal concentrations?
Acts on renal nephron
- Increase permeability of renal distal convoluted tubule/ collecting ducts to water
- More water reabsorbed from tubule
- Reduced urine output + more concentrated
- Restoration of blood osmolarity and volume
What is the main action of vasopressin (ADH) at higher concentrations?
Acts on blood vessels
- Constricts blood vessels
–> Leads to raised blood pressure
What disease is caused hyposecretion of vasopressin (ADH)?
Diabetes Insipidus
What is Diabetes Insipidus?
Hyposecretion of vasopressin (ADH)
What are the effects of diabetes insipidus?
Less water uptake in the distal tubule in the nephron
- Increased urination
- Increased plasma osmolarity
- Dehydration
What are the effects of hyposecretion of vasopressin (ADH)?
Less water uptake in the distal tubule in the nephron
- Increased urination
- Increased plasma osmolarity
- Dehydration
What are the symptoms of diabetes insipidus?
(1) Polyurea - Increased and diluted urine
(2) Polydipsia - thirst and excessive drinking
What are the symptoms of hyposecretion of vasopressin (ADH)?
(1) Polyurea - Increased and diluted urine
(2) Polydipsia - thirst and excessive drinking
What are the potential causes of diabetes insipidus?
(1) Neurogenic - brain trauma
(2) Nephrogenic - Kidney insensitivity to vasopressin (ADH)
What is the treatment for diabetes insipidus?
Replacement therapy with desmopressin
What is desmopressin?
A synthetic vasopressin (ADH) analogue
What is the treatment for hyposecretion of vasopressin (ADH)?
Replacement therapy with desmopressin
What is the route of administration for desmopressin/ other vasopressin (ADH) replacement therapy?
Usually a nasal spray
Can also be injected (IM/ IV/ SC)
OR orally active form at a much higher dose
What is SIADH?
Syndrome of inappropriate ADH
(Hypersecretion of vasopressin {ADH})
What are the symptoms of SIADH?
(1) Decrease in urination frequency
(2) Excessive fluid retention
What are the physiological causes of SIADH?
(1) Cold
(2) Stress
(3) Anxiety
(4) Pain
(5) Trauma
What are the pathiological causes of SIADH?
(1) ADH-secreting tumour - can be primary/ ectopic
(2) Brain damage/ disorder
What is a primary tumour?
A tumour in the intended secreting gland
What is an ectopic tumour?
A tumour in a region/ tissue that does not usually secrete hormones
What is the treatment for SIADH?
(1) Limit fluid intake to 500mL/ day
(2) Surgical removal of tumour
(3) Treatment course of demeclocycline (antibiotic)
- Has a side effect of blocking vasopressin (ADH) at kidney
Why is SIADH treated with demeclocycline?
The antibiotic demeclocycline has the side effect of blocking vasopressin (ADH) action at kidney
What is the biological function of oxytocin?
(1) Used to induce uterine contractions during parturition (giving birth)
(2) Milk ejection reflex
What does parturition mean?
The process of giving birth
What is a drug/ synthetic form of oxytocin?
Syntocin
What is syntocin?
Synthetic oxytocin
How does oxytocin induce childbirth?
Induces contraction of the uterine smooth muscle
What is the role of oxytocin in the milk ejection reflex?
Causes contraction of smooth muscle cells (myoepithelial cells) surrounding the milk ducts of mammary glands
What is another name for a smooth muscle cell?
Myoepithelial cell
What is a myoepithelial cell?
A smooth muscle cell
Which cells in the mammary gland respond to oxytocin?
Myoepithelial cells (smooth muscle cells)
Which cells in the mammary gland respond to prolactin?
Epithelial milk-secreting cells
What are the stages of the neuroendocrine reflex controlling milk-ejection?
(1) Suckling of nipple
(2) Sensory nerves -> Spinal Cord -> Brainstem -> Oxytocin-producing magnocellular neurones
(3) Oxytocin release from nerve terminals in posterior pituitary
(4) Oxytocin transported to myoepithelial cells lining the alveoli of the mammary gland
(5) Contraction of myoepithelial cells raises alveoli pressure to squeeze milk into ducts
(6) Sudden rise in intramammary pressure can cause milk to squirt
What type of feedback is involved in the milk-ejection reflex?
Positive feedback, due to oxytocin
