Endocrine system Flashcards
What is the structure of the musculoskeletal system?
Made of bones, joints, cartilage, ligaments, tendons, nerves and blood vessels
What is the axial skeleton?
Skull, vertebrae and ribs
What is the appendicular skeleton?
Limbs, pelvis, scapula and calvicke
What are the 4 types of bone cells?
Osteogenic - stem cells into osteoblast
Osteoblast - forms bone tissue
Osteocyte - maintains bone tissue
Osteoclast - reabsorption and destruction of matrix
What is ossification?
Skeleton develops from embryonic mesenchyme
Cells condense
Inter-membranous ossification
Endochondral ossification
How do bones grow?
Cartilage continually grows and is replaced by bone
What are the 4 steps of bone reformation?
- Hematoma formation
- Callus formation
- Callus ossification
- Bone remodelling
What are the three main types of joint?
- Synovial
- Fibrous
- Cartilaginous
What are the 6 subtypes of synovial joint?
- Planar
- Hinge
- Pivot
- Condyloid
- Saddle
- Ball and socket
What is osteoarthritis?
Thinning cartilage causes bones to rub together
What is rheumatoid arthritis?
Swollen and inflamed synovial membrane causing bone erosion
What is the importance of calcium?
Most abundant in body
A YA has 1.1 kg of calcium in body
99% in skeleton
What are the three ways calcium distributed in plasma?
Protein bound
Complexed
Free ionised
What are the 6 functions of calcium?
Nerve function
Muscle contraction
Blood clotting
Skeletal mineralisation
Cellular metabolism
Cell signaling
What is parathyroid hormone?
produced by chief cells of parathyroid gland
single chain polypeptide MW9500
How is PTH secretion regulated?
Ca2+ acting via the calcium sensing receptor
In the long term, calciferol acts directly on the gland
What does PTH do in the kidney?
Stimulates Ca2+ reabsorption in distal
Inhibits PO43- reabsorption in proximal
What does PTH do in the bone?
Stimulates effluent of Ca2+ from exchanging pool
Increased activity of osteoclasts
What is calcitriol?
Active metabolite of vit D3
What are the actions of calcitriol?
- Stimulates absorption of Ca2+ and PO43- in GI tract
- Increases activity of osteoclasts in bone
- faciliatates Ca2+ reabsorption in kidneys
What is calcitonin?
Single chain polypeptide MW3500
Secreted by paradoxical at C cells of thyroid gland
What are the actions of calcitonin?
- Stimulates absorption of Ca2+ and PO43- in GI tract
- Increases activity of osteoclasts in bone
- faciliatates Ca2+ reabsorption in kidneys
What is hypercalcaemia?
Associated with XS parathyroid hormone
e.g. tumour of parathyroid gland
Affects bones, kidneys, GI tract as well as neurological symptoms
What is hypocalcaemia?
Lack of parathyroid hormone effect e.g. PTH resistance
Lack of vitamin D effect e.g. intake, drug interaction
Symptoms related to neuromuscular excitability
Long term lack of vitamin D affects bone growth
Examples: osteomalacia, rickets, osteoporosis
What are the three classes of hormone?
Amino acids/Amines
Peptides and proteins
Steroids
What are some examples of peptide hormones?
Short amino acid chains e.g.
ADH (9 AA)
Oxytocin (9 AA)
Polypeptides e.g.
Insulin (135 AA)
Prolactin (198 AA)
What are 3 amide hormones?
Catecholamines derived from tyrosine
adrenaline, noradrenaline
Thyroid Hormones also derived from tyrosine
thyroxine, triiodothyronine
(Indoleamines derived from tryptophan
Melatonin)
What are some examples of protein hormones?
Thyroid stimulating hormone
Follicle stimulating hormone
Growth hormone
What is endocrine communication?
Messages disseminated from glands to effector via circulation
Relatively slow transfer of information
Can be long lasting
All cells contacted, specificity conferred by receptors
What ar the 4 types of endocrine disorders?
- Hypo-secretion
e.g. type I diabetes - Hyper-secretion
e.g. pancreatic endocrine tumour - Hypo-responsive
e.g. insulin resistant type II diabetes - Hyper-responsive
e.g. hyperthyroidism
What are beta-cells?
produce and release insulin
stimulates glucose utilization and uptake
What are alpha-cells?
produce and release glucagon
increases breakdown of glycogen and glucose release
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What are sigma-cells?
produce and release somatostatin
suppresses GI motility, and release of insulin and glucagon
What are the two actions of insulin?
Carbohydrate and lipid metabolism?
What is glucagon?
alpha-cells of islets synthesize and release glucagon
A peptide hormone (29 amino acids)
Released when blood glucose falls
the “counter-regulatory” hormone to insulin
stimulates glycogenolysis
promotes gluconeogenesis
increases breakdown of fats
What is hypoglycaemia?
Blood glucose < 3 mM (normal 4-6 mmol/L)
Uptake of glucose by glucose-dependent tissue not adequate to maintain tissue function
CNS very sensitive
impaired vision
slurred speech
staggered walk
mood change
confusion
coma
death
What are Suprachiasmatic neurones?
receive retinal innervation and synchronize circadian rhythms in the light-dark cycle
What are Neurosecretory cells?
responsible for release of regulatory hormones to control pituitary gland
What are the 4 trophic hormones?
Thyroid Stimulating Hormone
AdrenoCorticoTrophic Hormone
Follicle Stimulating Hormone
Luteinizing Hormone
What are the 2 primary hormones?
Growth Hormone
PRoLactin
What are the effects of growth hormone?
Increase cell size, number and differentiation
Stimulate protein synthesis
Stimulate fat utilization
Alter carbohydrate metabolism
What are somatomedins?
small proteins produced by the liver in response to GH (insulin-like growth factors)
at least 4 produced - somatomedin C is most important
long half life (20 hrs) compared to GH (<20 mins)
How is growth hormone secreted?
Released in response to growth hormone-releasing hormone (GHRH)
Release decreased by growth hormone-inhibiting hormone (GHIH or somatostatin)
Both released from ventromedial hypothalamus
GH is regulated by a short feedback loop
Controlled by many factors: sleep, exercise, stress
What can be caused by a GH deficit?
Dwarfism - may be
general anterior pituitary dysfunction -
specific GH deficit
normal GH but heriditary somatomedin deficit
Accelerated aging - loss of growth hormone after adolescence
What can be caused by a GH excess?
Gigantism – early life pituitary tumour
Acromegaly- pituitary tumour after adolescence
What are the effects of medullary catecholamines
Virtually the same as direct activation of sympathetic nerves except
last much longer (minutes)
effects generalized to all cells with and/or -receptors (GPCRs)
Major physiological effect is on cardiac output and cellular metabolism due to greater effect of AD than NA at -receptors
What are the actions of adrenal catecholamines?
- Increased release of glucose, fatty acids, increased heart rate and blood pressure
What are the actions of aldosterone?
Stimulates the reabsorption of Na+ /excretion of K+ in the cortical collecting ducts
Decreases the ratio of [Na+] to [K+] in sweat and saliva
Increases the reabsorption of Na+ in the colon and excretion of K+ in the faeces
What are the three types of drugs that effect aldosterone actions?
Aldosterone antagonists
ACE inhibitors
ATII antagonists
What is addisons disease?
cortisol deficiency
- causes tendency towards immunodeficiency
- fatigue and anorexia
- hyperglycaemia and weightloss
- vasodilation, anaemia and hypotension
What are corticosteroids?
Cause rise in plasma glucose levels (release from liver and increased gluconeogenesis)
This causes increase in proteolysis, which in turn
can bring about muscle wasting, skin thinning
Cause fat redistribution (as in Cushing syndrome)
moon face, buffalo hump
Cause increased breakdown of triglycerides,
leading to a rise in plasma fatty acid levels
Suppress inflammation and immune responses
What is cushings disease?
cortisol excess
- hyperglycaemia
- decreased inflammatory response
- depressiopn and euphoria
How is thyroid hormone synthesised?
Cells actively accumulate iodide and iodinate tyrosine residues to form T3 and T4
Iodinated thyroglobulin enters lumen by exocytosis
Stored thyroglobulin re-enters follicle cells by endocytosis
Lysosomal enzymes release T3 and T4
Most (~90%) are “bound” by binding proteins in plasma
“Free” fraction of T3 and T4 can enter target tissues
What is TSH?
+ Iodine uptake from blood by stimulating expression of the ATP-dependent sodium/iodide transporter
+ TH synthesis by stimulating expression of thyroid peroxidase
+ Thyroglobulin internalization and breakdown by lysosomal proteases
What do thyroid hromones do?
Growth and development
Stimulate protein, carbohydrate and lipid metabolism
Regulate energy metabolism
Body temperature
Regulation of nervous system, cardiovascular, musculo-skeletal and reproduction
90 % of released hormone is T4
70-75% of both T3/T4 are bound by thyroid binding globulin, rest by thyroid binding prealbumin
Only unbound T3 (0.3%) and T4 (0.03%) can enter target tissues
Most of physiological effects of thyroid hormones are due to T3
Mitochondrial effects
++ size and number
++ ATP production
Nuclear receptor increases transcription and translation via TRE
Effect is generalized increase in enzyme synthesis
Nearly all cells have TH receptors - widespread effects
What are the physiological effects of TH?
- decreased weight, increased appetite
- increased motility of GI tract
- increased excitiability and thought speed
- increase in muscle force
- increased raet and depth of respiration
- increased. cardiac output
What is hyperthyroidism?
excess of TH
- decreased weight
- heat intolerance
- increased bowel movement
- nervousness and irritability
- weakness and tremor
- excess hair growth
- increased cardiac output
What is hypothyroidism?
TH deficiency
- increased body weight
- cold intolerance
- constipation
- mental sluggishness and fatigue
- muscle weakness and strength
- decreased hair growth
What are the ovarian functions?
Oogenesis
Maturation of the oocyte
Ovulation
Secretion of the female sex steroid hormones
What is Oogenesis?
Ovum production
Occurs monthly in ovarian follicles
Part of ovarian cycle
Follicular phase (preovulatory)
Luteal phase (postovulatory)
What is the function of the uterus?
Muscular organ
Mechanical protection
Nutritional support
Waste removal for the developing embryo and fetus
Uterine cycle involves changes in the uterine wall
What is the uterine wall made of?
Myometrium – outer muscular layer
Endometrium – a thin, inner, glandular mucosa
[Perimetrium – an incomplete serosa continuous with the peritoneum]
What are the stages of the uterine cycle?
Menses
Degeneration of the endometrium = Menstruation
Proliferative phase
Restoration of the endometrium
Secretory phase
Endometrial glands enlarge and accelerate their rates of secretion
What are the 4 hormones involved in the female reproductive system?
FSH
Stimulates follicular development
LH
Maintains structure and secretory function of corpus luteum
Oestrogens
Have multiple functions
Progesterones/ Progestogens
Stimulate endometrial growth and secretion
What are oestrogen receptors?
The receptor changes conformation due to the dissociation of heat shock proteins after oestrogen binds
The receptor undergoes dimerization in order for increased affinity to DNA
This oestrogen-receptor complex can now bind to specific DNA sites, called oestrogen response/ recognition elements (EREs).
What are progesterone receptors?
Nuclear receptors regulating gene transcription – like ER
There is a single gene that encodes the progesterone receptor – PR; bind to PREs
Two isoforms – PR-A and PR-B
Identical ligand binding
PR-B mediates the stimulatory effects of progesterone
What are the actions of oestrogens?
- stimulation of endometrium
- secondary sex characteristics
What are the actions of progesterones?
Produced in luteal phase, decreases GnRH production
Induction of secretory activity in oestrogen-primed endometrium
+ Viscosity cervical mucous
Promotes glandular breast development
+ Basal body temperature
What is menopause?
Menopause normally occurs 45-55 yrs
Menstruation becomes irregular & then ceases
Caused by “ovarian failure”
Gonadotropins secreted in greater amounts, because of loss of negative feedback
What are the 3 phases of menopause?
Perimenopause
Fluctuation in hormone levels
Can last 2-8 years
Menopause
Oestrogen levels drop
1 year after cessation of menstrual cycle
Postmenopause
Oestrogen levels continue to drop
What are the symptoms of menopause?
Hot flushes of skin
Night sweats
Palpitations
Low mood/anxiety
Impaired memory/brain fog
Recurrent headaches/ migraines
Vaginal atrophy
Development of osteoporosis
What is osteoporosis?
Oestrogen acts to maintain bone mineral density
There is a positive relation between maintenance of bone mass and HRT with oestrogen
Decrease rates of wrist, non-vertebral, vertebral, and hip fractures
Raloxifene – SERM that functions like oestrogen to maintain bone density
What is HRT?
Generally use “natural” oestrogen rather than more potent synthetic derivatives
Oestrogens + progestogens in women with an intact uterus
Combination preparations (tablet, patch) (cyclical)
Oestrogen only preparation (transdermal patch, gel, spray) PLUS progesterone (tablet, intrauterine device)
What are the effects of HRT?
HRT can reduce post-menopausal osteoporosis & vasomotor symptoms
Oestrogens LDL cholesterol levels but evidence mixed about risk of coronary heart disease
For most women the benefits of HRT outweigh the risk of breast cancer, blood clots, cardiovascular disease
What is the combined pill?
Ethinylestradiol or mestranol PLUS levonorgestrel/ desogestrel/ gestodene
Taken 21/28 days
Oestrogen – inhibits secretion of FSH via negative feedback on the pituitary
Progestogens – inhibit LH secretion and induces thickening of cervical mucus & thins endometrium
What are the side effects of COCs?
Mild side effects are mostly related to the oestrogen content
Nausea, vomiting
Weight gain (Na+/ fluid retention)
Mild hypertension
Breast tenderness
More serious (and rare) side effects:
Venous thromboembolism (oestrogen coagulation)
Cerebral haemorrhage/ embolism/stroke, myocardial infarction (especially in heavy smokers & 35+)
Increased risk of breast/cervical cancer
Amenorrhoea following withdrawal can last several months
What are POCs?
Norethisterone, levonorgestrel, ethynodiol
Taken continuously, effects include:
Cervical mucus becomes thick & sticky
Endometrium changes so implantation less likely
Weak negative feedback inhibition of LH release & ovulation
POC’s in some women can completely suppress gonadotrophin secretion & ovulation resulting in amenorrhoea.
What are 4 menstrual disorders?
Dysmenorrhoea
- painful periods
Menorrhagia
- heavy periods, excessive blood loss
Premenstrual syndrome
- physical, psychological, behvioural changes
Endometriosis
- long-term condition
What is emergency contraception?
Pregnancy can be prevented by short-term administration of a high dose of progestogen - the “morning after pill”, “plan-B”
Used within 72 h of unprotected intercourse it is 98% effective
Ulipristal is a PR modulator - effective within 5 days
Side effects: nausea, vomiting (can affect absorption), cardiovascular and metabolic effects, breast tenderness
What are antiprogestogens?
Mifepristone – PR antagonist
Used in combination with a prostaglandin - gameprost
“Medical abortion” - an alternative to surgical termination of pregnancy
