Suger 2 Flashcards
What is the purpose of the endocrine system?
Allows for integration of whole body physiology & rapid adaptive changes
Allows communication between the different cells & tissues
Long term maintenance of metabolic environment
What are the 8 main endocrine organs?
Pituitary gland Thyroid gland Breast Adrenal gland Kidneys Ovaries Uterus Testes
What are the 2 main types of hormone?
Peptide
Steroid
How are peptides synthesised?
Preprohormone made at ribosomes
Cleaved to form pro hormone by proteolytic enzymes in RER
Stored in vesicles
Where are the receptors for peptide hormones found?
Cell surface membrane of target cell
How do peptide hormones work?
Initiating other reactions in the cell’s cytoplasm
Where are steroids produced?
Adrenal cortex
Gonads
What are the steroid hormones derived from?
Cholesterol
Where are the receptors for steroid hormones found?
Intracellular
How do steroid hormones work?
Alter target cell’s gene expression & protein synthesis to change function & secretion of the cell
How are each of the main hormones found in the blood plasma?
Peptides - unbound, fast acting
Steroid - bound to proteins, slow acting
What are amines a derivative of?
Amino acid tyrosine
What are some examples of an amine?
Thyroid hormones
Adrenaline
Noradrenaline
Dopamine
What is the posterior pituitary gland made up of?
Neural tissue - axons of neutrons & their supporting glia
Connected to hypothalamus by pituitary stalk
What 2 substances does the posterior pituitary release & where are they made?
Vasopressin - supraoptic nuclei of hypothalamus
Oxytocin - paraventricular nuclei
What is the role of vasopressin/ADH?
Reabsorption of water from CD of kidneys by stimulating insertion of AQP2 aquaporin channels into the luminal membrane of the epithelial cells
What is the role of oxytocin?
Expression of milk from glands of breasts to nipples & promotes onset of labour
What is the anterior pituitary gland made up of?
Glandular epithelial tissue
What are hypophysiotrophic hormones?
Hormones that control the secretion of anterior pituitary hormones (which control the secretion of a hormone from another endocrine gland)
Sequence of 3 hormones
Where does the anterior pituitary gland recieve its blood supply from?
Portal venous system from hypothalamus
What are the 6 main hormones that are secreted from the anterior pituitary?
FSH, follicle stimulating hormone LH, lutenising hormone GH, growth hormone, somatotrophin TSH, thyroid stimulating hormone, thyrotropin Prolactin ACTH, adrenocorticotrophin hormone
What are FSH & LH stimulated to be excreted by?
GnRH, gonadotrophin releasing hormone
What do FSH & LH do?
Stimulate gonads to release sex hormones
What is GH stimulated to be excreted by?
GHRH, growth hormone releasing hormone
What does GH do?
Stimulates release of a growth-promoting peptide hormone, insulin-like growth factor 1
What is TSH stimulated to be excreted by?
TRH from hypothalamus
What does TSH do?
Stimulates thyroid to secrete thyroxine & triiodothyronine
What is prolactin stimulated to be excreted by?
Naturally inhibited by dopamine
Levels of dopamine drop, secretion increases
What does prolactin do?
Stimulates milk production
Stimulates development of mammary glands
What is ACTH stimulated to be excreted by?
CRH, corticotrophin releasing hormone
What does ACTH do?
Stimulates adrenal cortex & its secretion of cortisol
What are the 2 lobes of the thyroid gland connected by & which cartilages do they sit in front of?
Isthmus
Tracheal cartilages 2-4
What is the blood supply to the thyroid gland?
Superior & inferior thyroid arteries
Why does the thyroid gland need a rich blood supply?
Uses iodine to make hormones
What is the thyroid gland histologically made up of?
Numerous follicles
Walls - follicular cells
Lumen - contains colloid, protein rich material
What does the thyroid gland produce?
Thyroxine, T4
Triiodothyronine, T3
What hormone does the thyroid gland respond to?
TSH from the anterior pituitary
How is iodine transported into a follicular cell?
- Large negatively charged iodine ions circulating in blood co-transported from interstitial fluid into cytoplasm of follicular cells with Na+
- Too large to diffuse out (iodine trapping), so diffuse down concentration gradient to luminal surface of follicular cell
How are the thyroid hormones initially formed?
- large amount of enzyme thyroglobulin in colloid
- iodine ions rapidly oxidised by enzyme thyroid peroxidase to form free iodine radicals
- attached to tyrosine, an amino acid in the structure of the thyroglobulin enzyme
- tyrosine & 1 iodine = moniodotyrosine (MIT)
- tyrosine & 2 iodines = diiodotyrosine (DIT)
What are T4 & T3 formed from?
T4 = DIT + DIT T3 = DIT + MIT
How are the hormones transported from the colloid?
Portions of luminal membrane of follicular cells engulf the thyroglobulin structures by endocytosis
Proteolytic enzymes in lysosomes release T3 & T4
What does enzyme deiodinase do in the target cells?
Converts T4 to T3
thyroid makes more T4 then T3
What are some of the things that thyroid hormones regulate?
Breathing HR Central & peripheral NS Body weight Muscle strength Menstrual cycles Body temperature Cholesterol levels ...
Do receptors have a higher affinity for T3 or T4?
T3
What are the 3 main cell types of the islets of Langerhans?
Beta cells
Alpha cells
Delta cells
What do beta cells secrete & in response to what?
Insulin
High blood glucose levels
What do alpha cells secrete & in response to what?
Glucagon
Low blood glucose levels
What do delta cells secrete & what does it do?
Pancreatic somatostatin
Inhibitory effect on release of insulin & glucagon
What is GH release inhibited by?
Somatostatin from hypothalamus
What does glucagon do? (3)
Increases blood glucose by:
- increasing hepatic output of glucose by increasing gluconeogenesis & glycogenolysis
- reducing peripheral uptake of glucose from the bloodstream
- stimulation of peripheral release of gluconeogenic precursors (e.g. glycerol, amino acids) through stimulation of lipolysis & muscle breakdown
What are the 2 phases of insulin release?
First - rapid, from vesicles
Second - slower, release as made
What are the 8 steps of insulin release?
1) increase in amount of glucose transported into beta cells through GLUT2 glucose transporter protein when increased glucose levels in blood
2) enters glycolytic pathway & ATP moves into cell
3) extra ATP binds to K+ channels on cell surface membrane of beta cell, closing channels
4) K+ stops flowing out of cell, membrane potential altered
5) voltage-gated Ca2+ channels open
6) Ca2+ flows in
7) causes conformational changes to SNARE proteins on membranes of vesicles that contain insulin
8) vesicles can now bind with cell surface membrane & release insulin into interstitial fluid
What are incretins?
Hormones released from the gut that stimulate the release of insulin
Why is insulin greater following oral consumption of glucose compared to intravenous glucose?
Incretins stimulate the release of insulin
What does insulin do? (3)
Decreases blood glucose by:
- suppression of hepatic glucose output, decreasing gluconeogenesis & glycogenolysis
- increase glucose upstake by insulin-sensitive tissues for glycogen & protein & fatty acid synthesis
- suppression of lipolysis & breakdown of muscle
How is insulin uptaken by cells? (4 steps)
1) binds to insulin receptors on cell surface membrane (as peptide hormone)
2) intracellular signalling cascades take place
3) vesicles in cytoplasm that store GLUT4 glucose channels are mobilised to the cell surface membrane
4) increased GLUT4 results in more glucose being taken up by the cells
What are the 2 phases of the menstrual cycle?
Follicular - first 14 days
Luteal - 14 days after ovulation
What does the rise of FSH cause?
Primordial follicles in the ovaries to begin to develop
What occurs as the follicles begin to develop?
Their granulosa cells begin to secrete oestrogen
What are the effects of oestrogen during the cycle? (2)
Negative feedback effect on anterior pituitary when low levels in first 10 days
Positive feedback effect on release of LH when levels increase
What does the LH surge cause?
Ovulation
Oocyte expelled from dominant follicle in ovary
Corpus luteum remains
What does the corpus luteum produce?
Oestrogen
Progesterone
What is the effect of progesterone?
Negative feedback effect on hypothalamus
Inhibits secretion of GnRH
Thus inhibits secretion of FSH & LH
How does the cycle restart?
Corpus luteum degenerates
Less -ve feedback on hypothalamus
What does an oocyte begin as?
Primordial follicle
One primary oocyte surrounded by a single layer of granulosa cells
When does the primordial follicle develop into the primary follicle?
When oocyte develops & becomes fully grown
Granulose cells begin to proliferate & become multilayered
What separates the oocyte from the innermost later of granulosa cells?
Zona pellucida
How does the oocyte maintain its meiotic arrest?
Granulosa cells inner layer delivers nutrients
Cytoplasmic processes transverse the ZP & form gap junctions with oocyte
What is the theca of the follicle?
Differentiated layers around outside
Involved in oestrogen secretion from granulosa cells
What is the antrum & why does it develop?
Fluid filled space in midst of granulosa cells
Secretions of granulosa cells cause it to develop
Follicle from pre-antral to early antral
How many antral follicles become the dominant follicle that continues to develop?
1
What causes the dominant follicle’s growth? (2)
Expansion of antrum due to increase in fluid
Granulose cells closest to oocyte form mound like structure, cumulus oophorus
What happens to the oocyte as ovulation occurs?
Undergoes first meiotic division
Cumulus oophorus separates it from granulosa cells so can float freely in antrum
How is the oocyte released from the follicle?
Digestive enzymes break down granulosa cells, leaving ZP & cumulus oophorus
What do trophoblasts of the developing structure secrete?
Human chorionic gonadotrophin, hCG
glycoprotein
What are the roles of hCG? (3)
Prevents degeneration of corpus luteum
Strongly stimulates secretion of steroid hormones from CL
Allows continued secretion of oestrogen & progesterone from corpus luteum until placenta developed enough to take over
What is progesterone’s role in pregnancy? (2)
Inhibits uterine contraction (to prevent premature birth)
Continues to have negative feedback effect on GnRH
What are the 2 reasons for preventing a menstrual cycle during pregnancy?
Prevents miscarriage
Builds up endometrium of uterus in preparation for development of placenta
What is oestrogen’s role in pregnancy? (3)
Stimulates development of uterine muscle (myometrium)
Regulates levels of progesterone
Prepares breasts for lactation
Why does the placenta need to get androgens from the mother’s ovaries & adrenal glands?
Androgens precursor for oestrogen
Placenta does not have enzymes for synthesis
Where else does the placenta get androgens from?
Foetus’s adrenal glands & liver
What is the role of relaxin in pregnancy?
Limits uterine contractions
Softens cervix
What is the role of oxytocin in pregnancy?
Stimulates contraction of smooth muscle of myometrium
In turn stimulates further secretion of oxytocin
Positive feedback loop
What are prostaglandins involved in in pregnancy?
Initiation of labour
What are some of the physiological changes to the CV system in pregnancy?
CO increase TPR decreases BP decreases overall Heart displaced & becomes larger Blood flow to uterus increases Risk of varicose veins increases Blood volume increases Erythrocyte count increases Physiological anaemia of pregnancy (erythrocyte count doesn't increase as much as volume)
What are some of the non-CVS physiological changes in pregnancy?
Weight gain Breathing more shallow & frequent Linea nigra Striae gravidarum (stretch marks) Darkening of skin around abdomen & areoli Acid reflux more common Lumber hyperlordosis
How does the uterus adapt for paturation?
Grows due to increased cell division & hypertrophy of individual myometrial cells
What is the disconnected arrangement of the myometrial cells maintained by?
Progesterone
What stimulates the synthesis of connexion proteins & thus gap junctions between myometrial cells?
Oestrogen
What stimulates the production of placental prostaglandins?
Oestrogen
What do placental prostaglandins act to do?
Act with oestrogen to stimulate the synthesis of enzymes that mediate the breakdown of collagen fibres that form the cervix (cervical ripening)
What stimulates the synthesis of receptors for the hormone oxytocin?
Oestrogen
What is foetal stress?
Foetal head pressing on the cervix
What does foetal stress stimulate?
Release of ACTH
Cortisol thus secreted
What are cortisol’s effects on the placenta?
Decrease in oestrogen secretion
Decrease in progesterone secretion
Increase in prostaglandin secretion
What does the increase in secretion of prostaglandins cause?
Uterine muscles to start to push the foetus down
Stretches cervix & stimulates nerve fibres
Stimulates production & secretion of oxytocin
What are the seminiferous tubules make up of?
Basement membrane (on which sit fibroblast cells)
Sertoli cells
Spermatogonia (sperm stem cells)
Where are Leydig cells found & what do they produce?
Interstitial space between tubules
Testosterone
What are the 2 types of daughter cell produced from the mitosis of spermatogonia?
Type A
Type B
What occurs to type A cells?
Remain outside BTB
Continue to undergo mitosis to produce more spermatogonia
What occurs to type B cells?
Primary spermatocytes
Pass through BTB to move in towards lumen of seminiferous tubule
Will develop into spermatozoa
What 2 steps occur before spermiogenesis?
Primary spermatocytes undergo first stage of meiosis into secondary spermatocytes
Secondary spermatocytes undergo second stage of meiosis to form spermatids
What is spermiogenesis?
Process by which spermatids develop into immature spermatozoa
What steps of oogenesis occur before puberty?
Oogenia undergo mitosis until ~7 months
Develop into primary oocytes
Begin meiosis I
Meiotic arrest between prophase I & metaphase I
What does the first meiotic division produce?
Haploid secondary oocyte (ovulated)
Smaller primary polar body (almost no cytoplasm)
What does the second meiotic division of the fertilised secondary oocyte produce?
Ovum
Second polar body
What do the ovum & spermatozoa join to make?
Zygote
What causes puberty in males?
Increase in ACTH secretion
Androgens stimulated to be produced
Androgens stimulate early pubic & axillary hair growth
Act alongside GH & IGF-1 to cause growth spurts
What are the male secondary sex characteristics? (puberty)
Facial & body hair
Deepening of voice due to growth of larynx
Masculine pattern of fat distribution
Thickening of skin oil gland secretionns
How are puberty & the hypothalamic-anterior pituitary-gonadal axis related?
Increase in secretion of GnRH
Increase in secretion of LH & FSH
Seminiferous tubules stimulated to secrete testosterone & DHT
What causes puberty in females?
Increase in GnRH secretion
Increase in pulsatility amplitude of secretion
Why does menopause occur?
Depletion of primordial follicles
What are the hormonal changes during menopause?
Ovaries essentially fail
Oestrogen levels fall
No regulation of GnRH/FSH/LH
What are some of the symptoms of the menopause?
- Atrophy of genital organs & breasts
- Thinning & dryness of vaginal epithelium
- Significant decrease in bone mass (osteoporosis risk)
- Hot flashes
- Increased risk of CV diseases (oestrogen has a protective effect)
- Physiological symptoms: irritability, lethargy, forgetfulness, less libido
What are the 2 types of receptor in the bladder wall (detrusor wall)?
Muscarinic M3
Beta-adrenergic B3
What do muscarinic M3 receptors respond to?
ACh from parasympathetic NS
What do muscarinic M3 receptors receive innervation from?
Efferent fibres of pelvic splanchnic nerve - from sacral region
What do beta-adrenergic B3 receptors respond to?
Noradrenaline from sympathetic NS
What do beta-adrenergic B3 receptors receive innervation from?
Hypogastric nerve - from thoracolumbar region
What receptors does the internal urethral sphincter have in males?
Alpha-adrenergic A1 receptors (innervated by hypogastric nerve)
What receptors are in the external urethral sphincter?
Nicotonic
What do the receptors in the external urethral sphincter respond to?
ACh released from pudendal nerve
What detects it when the bladder is empty & where do these signal go?
Sensory afferent fibres of pelvic nerve Carry slow impulses to sacral cord Up spinal cord Thoracolumbar region Hypogastric nerve
What does the hypogastric nerve release & what does this do?
Noradrenaline release
- B3 receptors in detrusor - relax
- A1 receptors in internal urethral sphincter (M) - contract
How is the pontine micturition centre involved with the empty bladder? (3)
- Impulses sent down spinal cord to hypogastric nerve, adding to impulses
- Inhibits impulses to efferent fibres of pelvic splanchnic nerve so no activation of M3 receptors - no contraction
- Impulses sent along pudendal nerve - contraction of external urethral sphincter
What occurs when the bladder is full?
Detrusor muscle stretched
Stimulation of afferent fibres
More rapid impulses
How is the pontine micturition centre involved with the full bladder? (3)
- Inhibits impulses down hypogastric nerve - no relaxation of detrusor & no contraction of internal sphincter
- Stimulate efferent fibres of pelvic splanchnic nerves - contraction of detrusor
- Inhibition of pudendal nerve - no contraction of external sphincter
What does the hypogastric nerve do in micturition when stimulated?
Relaxes detrusor
Contracts internal urethral sphincter
What does the pelvic splanchnic nerve do in micturition when stimulated?
Contraction of detrusor
What does the pudendal nerve do in micturition when stimulated?
Contraction of external urethral sphincter
What is the voiding reflex?
Voiding (emptying) of bladder continues uninterrupted until bladder is empty
How does the voiding reflex occur?
Afferent fibres continue to send impulses during urination
Stimulate interneuron within sacral segment
Impulse to efferent pelvic splanchnic nerve
Continued contraction of detrusor
What are the roles of progesterone with the endometrium in the menstrual cycle? (3)
- Maintains integrity during menstrual phase
- Causes cells to become more complex in preparation for implantation in secretatory phases (from corpus luteum)
- No pregnancy, levels fall so endometrium shed
What are the roles of oestrogen with the endometrium?
Stimulates endometrial growth in proliferative phase
What are the roles of progesterone with the cervix?
- cells secrete thick mucus in infertile phase
* cervical os closed
What are the roles of oestrogen with the cervix?
- stimulates cervical cells to secrete fertile-type mucus
* cervical os open
What is the epithelia of the tubuli recti?
Simple/stratified cuboidal
What is the epithelia of the recti testes?
Simple cuboidal
What is the epithelia of the efferent ductules?
Pseudostratified columnar
What is the epithelia of the epididymis?
Pseudostratified columnar with sterocilia
What is the epithelia of the vas deferens?
Pseudostratified columnar
What is the epithelia of the ejaculatory duct?
Simple columnar
What is the epithelia of the bulbourethral gland?
Simple columnar
What is the epithelia of the seminal vesicles?
Pseudostratified columnar
What is the epithelia of the ovaries?
Simple cuboidal
What is the epithelia of the fallopian tubes?
Simple columnar & ciliated
What is the epithelia of the vagina?
Stratified squamous & non-keratinised
What is the epithelia of the endometrium?
Simple columnar & ciliated
What is the epithelia of the labia majora/minora?
Stratified squamous keratinised (skin)
What is the epithelia of the endocervix?
Simple columnar
What is the epithelia of the ectocervix?
Stratified squamous & non-keratinised