SUGER Flashcards
What capillaries make up the glomerulus? and therefore the endothelial lining is
Fenestrated capillaries
fenestrated
What arteriole is blood fed into glomerulus
Afferent arteriole
What arteriole drains the glomerulus
efferent arteriole
How many layer are there within the glomerular basement membrane
3
Endothelial side
Lamina Rara Interna (Heparan sulfate)
Lamina Densa (Type 4 collagen, laminins)
Lamian Rara Externa (Heparan sulfate)
Podocyte layer
What is/isn’t allowed to enter the bowman’s capsule
Formed elements not allowed + negatively charged substances
Elements such as H2O, small proteins, nutrients + positively charged substances allowed in
What are the layers of the bowman’s capsule ?
Parietal (simple squamous epithelial cells)
Visceral (podocytes)
What is the space between podocytes called?
Filtration slits
What protein spans across adjacent podocytes?
Nephron because they span across filtration slits they are called Nephron diaphragm
What is the role of a mesangial cell?
Phagocytose any macromolecule that gets stuck in the slit diaphragm
Contractile ability - afferent/efferent arterioles
Bind to JG cells to secrete renin
What is glomerular filtration rate?
Plasma volume that is being filtered out of glomerulus and into Bowmans capsule for every 1 minute 125ml/min
What factors affect glomerulus filtration rate?
Net filtration pressure: Pressing forcing out - Pressure forcing in
Pressure forcing out = glomerular hydrostatic pressure + colloid osmotic pressure
Pressure forced in = colloid osmotic pressure + capsular hydrostatic pressure
Permeability of glomerulus + Surface Area= Filtration Coefficient
GFR= NFP x KF
Relationship between NFP & GFR
Directly proportional
Relationship between GFR and Filtration coeffeicent
Directly proportional
What makes up the filtration co-efficient
surface area + permeability of glomerulus
What is the GHP and BP relationship
directly proportional and therefore dependent on systemic circulation
What is osmolality
Volume of particles per kg of solvent
OSMOLALITY = moles/kg
What is tubular secretion
Substances flowing from blood to kidney tubules (active transport)
What is tubular reabsorption
Substances flowing from tubules to blood
Active or passive
Proximal tubule bulk reabsorption
3Na+/2K+ ATPase pumps
Secondary Active transport: Na+ &Glucose/amino acids/lactate channel
Secondary Active transport: Na+ & H+ pump. H+ combines with HCO3- in a proximal convoluted tube to form H2CO3. This then with the enzyme carbonic anhydrase goes to become H20 + CO2
Paracellular transport
Urea is also reabsorbed via lipid
What substances have a 100% reabsorption
Glucose
Amino Acids
Lactate
What is obligatory water reabsorption
When the water is following the actual salt into the blood
By which transport mechanism is drugs undergo tubular secretion
Active transport
What is the importance of tubular secretion
Might not be able to get rid of that substance because it got reabsorbed too much/or couldn’t filter/lipid-soluble
What happens to the osmolality as you go from renal cortex to renal medulla
Increases therefore have less H20 in comparison to solutes which is high = hypertonic
What two things make up the loop of Henle
Ascending limb
Descending limb
What makes up the nephron
Bowman’s Capsule, Glomerulus, PCT, DCT, Loop of Henle
What is the name of the cotransporter found in ascending limb of Loop of Henle?
Na+/K+/Cl- co transporter
Reabsorbs all of Na+ and Cl- and some of K+ into blood
What is the Counter Current Exchange Mechanism
When the ascending limb goes up and pumps out Na+, K+, Cl- with the cotransporter making the medullary interstitial space salty.
This causes the water travelling down the descending limb to leave via aquaporin 1 (obligatory water reabsorption)
Water leaves the descending limb until the kidney tubules plasma osmolality is equal to descending limb isotonic
Why cant solutes leave out of the descending limb
Or water leave ascending limbs
The descending limb is impermeable to solutes
The ascending limb is impermeable to water
What is the osmolality in the distal convoluted tube
Hypotonic as most of the solutes have left through the cotransporter in comparison to the plasma osmolality
What is the vasa recta
peritubular capillary in the medulla
branch of efferent arteriole
slow blood flow
Parallel to the loop of Henle
Involved in the counter current multiplier system
What happens in the vasa recta
There is a high concentration of NaCl in the instertial fluid. Moves into the vasa recta as the osmolality increases as you go down vasa recta. At the same time high conc of H20 moves from vasa recta to instertial fluid
As osmolality decreasesas you go up vasa recta NaCl is being pushed out. H2O moves back in
Counter Current Multiplier mechanism significance
Prevents the rapid removal of sodium chloride from the medullary interstitial in order to maintain sality gradient
Delivers O2 to tissues
How is calcium reabsorbed in the early distal convoluted tubule
Low Ca+ levels detected by chief cells causes parathyroid to secrete parathyroid hormone.
Parathyroid hormone binds to receptors distal convoluted tubule then causes adenyl cyclase mechanism opening up Ca2+ channel.
Calcium reabsorbed then by secondary calcium channel
What drug inhibits the sodium chloride symporter in the early distal convoluted tubule
Thiazide
Its a diuretic
What does the adrenal gland secrete
Aldosterone
Stimulates: Angiotensin 2, Na+ concentration
Inhibit: Low K+ levels
What is distal convoluted tubule impermeable to?
Water
What are principal cells responsible for?
Maintaining mineral balance in cells
What are intercalated A and B cells
maintaining acid-base balance
Where intercalated cells found
Collecting duct
What do intercalated A cells secrete
What do intercalated B cells secrete
Acid
Base
What secretes ADH
Pituitary gland
What stimulates the release of ADH
Increase in osmolality
Angiotensin 2
What cells do ADH act on and where can the be found?
Collecting duct
Act on principal cells
What cells make up collecting duct
Principal cells
Intercalated cells
What happens once ADH binds to receptor of principal cells
Stimulates Gs protein
Goes to adenyl cyclase and converts ATP in cAMP
cAMP —-> pKa
pKa results in the fusion of vesicles containing aquaporins to go to collecting duct membrane
What ions depend on the hormone secreted and therefore reabsorbed into blood stream.
Where can this be found
Principal cells
Amount of Aldosterone present depends on Na+ that is being reabsorbed in late distal convoluted tubule
What is urea recycling
urea is secreted at the last part of the collecting duct via facilitated diffusion and gets reabsorbed by ascending limb.
Importance:
1, Make concentrated urine
2. Wants to contribute to medullary interstitial gradient
What happens to urine
Most goes down collecting tubule
Some gets recycled
What is absorbed by Proximal convoluted tube
Na+ (65%)
H2O (65%)
HCO3- (90%)
K+ (60%)
Cl- (50-60%)
Ca+ (60%)
Urea (50%)
Glucose, Amino Acids, Lactase (100%)
Vasa recta
parallel to loop of Henle
What is secreted into Proximal Convoluted tube
Drugs
H+
NH4+
Creatinine
=All require ATP
What is absorbed by Loop of Henle
Descending limb
25% water
Ascending limb
Na+ : 25%
K+ : 30%
2Cl- : 30%
What happens in parietal cell of distal convoluted tube when there is low bp
Zona glomerulosa secretes aldosterone
Stimulates genes and secretes 3 proteins in principal cell
One of the proteins allows sodium to enter the principal cell
Another protein allows 3Na+/2K+
Another one is to secrete potassium K+ into the late distal convoluted tube
ADH secretes causes aquaporin to open up
Intrinsic renal autoregulation
Myogenic mechanism
Tuboglomerular feedback system
Myogenic mechanism renal autoreg
High BP
⇡BP ⇢ ⇡G.H.P ⇢ ⇡G.F.R
⇡BP ⇢ ⇡Stretch⇢ ⇡contraction ⇢ ⇡vasoconstriction ⇢ ⇣GBF ⇢ ⇣GFR
⇡BP ⇢ ⇡G.F.R ⇢ high or low NaCl
high
Macula Densa
⇑Na+ ⇑Cl-
Adenosine
causes afferent arteriole to constrict by acting on smooth muscle cell- vasoconstriction smaller diameter and therefore lower GBF, less filtration and lower GFR lower NaCl
Inhibits JG cells to secrete renin
Macula Densa
⇓Na+ ⇓Cl-
NO PGI2
causes afferent arteriole to dilate by acting on smooth muscle cell - vasodilation larger diameter and therefore ⇡ GBF, ⇡ filtration and ⇡ GFR ⇡ NaCl
Stimulates JG cells to secrete renin
Extrinsic renal autoregulation
Sympathetic N.S (⇣SBP)
RAAS
Sympathetic nervous system
SNS gets activated when BP is really low
- Increases heart rate, increases stroke volume to increase cardiac output and bp
- Causes the vasoconstriction of the afferent arterioles to get more blood flow to other organs
- Causes vasoconstriction of the systemic arteries via alpha 1 receptor to increase bp triggers renin release from beta 1 receptors
Renin Angiotensin Aldosterone ADH System (RAAAS)
When there is low BP.
Low Bp ⇢ Low GFR
JG cells secrete more renin
renin causes angiotensinogen which is secreted by the liver to cleave and become angiotensin 1
Angiotensin 1 combine with Angiotensin converting enzyme (ACE) in the lungs and cleaves it to become angiotensin 2
AT2 affects other systems
What does angiotensin 2 do in PSNS? R.A.A.S
In CNS: Increase in thirst
In CNS: This causes the increase of ADH to be secreted by the `pituitary gland affecting the collecting tubule to become more permeable to H20. This increases the BV and therefore BP
In the adrenal cortex: binding to the zona glomerulosa secretes more aldosterone causing the increase of absorption of Na+ and H20 of parietal cells in DCT. This increases the BV and therefore BP
In kidneys: Binds to receptors of efferent arterioles and causes vasoconstriction and therefore increases GFR. Binds to cells of PCT via receptors and causes it to increase the reabsorption of sodium and water. Increasing BV and then BP
In systemic arterioles: causes vasoconstriction, increase in SVR, increase in BP
What does ADH do?
Put aquaporins in the tubular membrane, water can therefore be funnelled in tubular cells and into the blood.
What makes up the urinary bladder
Detrusor muscle
Internal & External urethral sphincter
urogenital diaphragm
Receptors in what muscle of the urinary bladder contain stretch receptos
Detrusor muscle
Mechanism of micturition of empty bladder
Receptors in the urinary bladder detect low action potential in the sacral spinal cord S2-S4
Stimulates neurons that will take these ascending fibres upwards into the thoracolumbar region of the spinal cord T11-L2 to synapse with preganglionic motor neurons
Then they synapse on the cell bodies of the inferior mesenteric ganglion
The hypogastric nerve carries impulses and attaches to detrusor muscles (relax). Secretes NE, which attaches to the receptor. NE also binds to receptors on the internal sphincter muscle (contract)
Impulses also carried up pons and cerebral cortex
This stimulates the pontine storage centre and inhibits the pontine micturition centre in the pons
impulses from the pontine storage centre and synapse with inferior mesenteric ganglion. They also carry down to preganglionic motor neurons.
Impulses carry to the detrusor muscle and secrete Ach, increasing Ca+ in muscles and causing contraction.
There are also impulses carried to the anterior ventral horn of the sacral spinal cord and synapse with cell bodies. The impulses travel to the pudendal nerve and bind to nicotinic receptor
Main contents of urine
95% H2O
rest are ions
uric acid
drugs
toxins
How much urine is stored in an empty bladder
10-20ml
What is it called when glucose is in urine
Glycosuria → diabetes mellitus
High amounts of protein in the urine
Caused due to an increase in BP glomerulonephritis, heart failure
>150mg/day urine 1st sign of renal disease
Name the 3 things to make up the Glomerular Filtration barrier.
- Fenestrated capillary endothelium.
- Double layer basement membrane.
- Foot processes of podocytes.
Name 5 factors that determine a molecule crossing the filtration barrier.
- Pressure.
- Size of the molecule.
- Charge of the molecule (negative molecules are repelled).
- Rate of blood flow.
- Binding to plasma proteins.
What force favours glomerular filtration?
Hydrostatic pressure of the glomerular capsule.
Name 2 forces that oppose glomerular filtration.
- Hydrostatic pressure of the bowman’s space.
- Oncotic pressure of the glomerular capsule.
Does the bowman’s space exert an oncotic pressure?
No. There are no proteins in the Bowman’s space.
What equation could be used to calculate the net glomerular filtration pressure?
HPgc - HPbs - πgc
What effect does vasoconstriction of the afferent arteriole have on GFR?
GFR will decrease as the HPgc decreases.
What effect does vasodilation of the afferent arteriole have on GFR?
GFR will increase as the HPgc increases.
What effect does vasoconstriction of the efferent arteriole have on GFR?
GFR will increase. Efferent arteriolar constriction tends to push blood back to the glomerulus and so increases the HPgc.
What effect does vasodilation of the efferent arteriole have on GFR?
GFR will decrease as the HPgc decreases.
What is tubuloglomerular feedback?
Macula densa cells of the DCT detect NaCl levels and use this as an indicator of GFR.
NaCl levels increase as GFR increases.
Where are the macula densa cells located?
They are epithelial cells found within the DCT. They sit between the afferent and efferent arteriole of the glomerulus.
How could you measure GFR?
Look at the excretion of a marker substance.
List 3 qualities necessary of a marker substance.
- Freely filtered.
- Not metabolised.
- Not reabsorbed or secreted.
What substance can be used clinically to estimate GFR?
Creatinine.
What is the usual value of the filtration fraction?
20%
Define renal clearance.
Volume of plasma from which a substance is completely removed by the kidney per unit time.
How much H2O do we intake in a day?
2.5L
How much salt do we intake in a day?
10g
What is the equation for plasma osmolality?
2(Na + K) + glucose + urea
How is tonicity regulated?
By controlling the H20 movement.
Is ADH a vasoconstrictor or a vasodilator?
Vasoconstrictor.
How is fluid volume regulated?
By controlling Na+ movement.
List the 3 main triggers for the release of Renin.
- Sympathetic stimulation.
- Low BP detected by afferent arteriole.
- Low Na+ detected by macula densa cells.
What is the function of ACE?
Converts angiotensin 1 into angiotensin 2.
What is the function of atrial natriuretic peptide (ANP)?
ANP is a renal vasodilator. It inhibits aldosterone release induced by Angiotensin 2 and it closes ENaC channels
What channels do loop diuretics target?
NKCC2
What channels do Thiazides target?
NCC
Name 3 types of drugs you could give to someone with hypertension.
- Diuretics.
- Vasodilators.
- ACE inhibitors.
Name 3 urinary buffers.
- Ammonium.
- Phosphate (commonest urinary buffer).
- Bicarbonate.
How does respiratory acidosis effect the ammonium buffer?
The uptake and synthesis of ammonia is increased.
Is renal compensation to an acid/base disturbance fast or slow?
Slow. Respiratory compensation is fast.
What is the renal compensation mechanism for respiratory acidosis?
Increased ammonia production. H+ secretion increases and HCO3- reabsorption increases.
What is the renal compensation mechanism for respiratory alkalosis?
H+ secretion decreases and HCO3- reabsorption decreases.
What is the respiratory compensation mechanism for metabolic acidosis?
Chemoreceptors are stimulated enhancing respiration. PaCO2 decreases.
What is the respiratory compensation mechanism for metabolic alkalosis?
Chemoreceptors are inhibited reducing respiration. PaCO2 increase.
What does erythropoietin (EPO) do?
Stimulates bone marrow, promotes RBC maturation.
What is the role of the Kidneys in Vitamin D activation?
Converts 25-OH D into 1,25-diOH D. (Enzyme: 1-hydroxylase)
What is the diff between a male and female urinary bladder
Female urethra doest have a prostate and an external sphincter
The urethra is also shorter
Receptors of urinary bladder involved in micturition
Detrusor muscle: M3 receptor & B3 receptor
Internal sphincter: alpha 1 receptor
External sphincter: nicotinic receptor
The three important efferent nerves involved in micturition
Comes from the sacral region: pelvic nerve (parasympathetic) Ach-> M3 receptor
Increased stimulation leads to contraction of the detrusor muscle
Comes from sacral region: pudendal nerve (somatic) Ach-> nicotinic
This leads to the external sphincter contract
SNS system: Presynaptic ganglion -> Post sympathetic fibre (Hypogastric) NA-> B3 receptor. relaxation of the detrusor muscle
Presynaptic ganglion -> Post sympathetic fibre (Hypogastric) NA-> alpha 1 receptor -> relaxation of internal sphincter
The sensory afferent nerve involved in micturition called
Pelvic nerve attached to detrusor muscle
Full bladder micturition
Voiding Reflex
Afferent nerve fibres send impulses goes to ventral grey horn → interneurons → parasympathetic efferent fibres causes contraction of detrusor muscle
What are the 4 main layers of the epidermis of the skin?
- Keratinised squames.
- Granular layer.
- Spinous layer (the thickest layer).
- Germinative layer.
What is the role of Filaggrin?
Produces natural moisturising factor.
Why are protease inhibitors in the skin important?
Protease inhibitors prevent the breakdown of corneodesmosomes.
What is the ideal pH of the skin?
5.5
What is the SRY protein called?
Testis determining factor: under its influence male development takes place.
What is the importance of testis determining factor?
Under its influence male development takes place.
What cells are responsible for secreting testosterone?
Interstitial cells of Leydig.
What is the blood supply to the upper 2/3 of the anal canal?
The superior rectal artery (branch of IMA).
What is the blood supply to the lower 1/3 of the anal canal?
The inferior rectal artery (branch of internal pudendal artery).
What part of the anal canal receives autonomic innervation?
The upper 2/3 (lower 1/3 is somatic innervation).
Which anal sphincter receives autonomic innervation and is involuntary?
The internal anal sphincter.
Which urethral sphincter is composed of smooth muscle?
The internal urethral sphincter.
When is the periaqueductal grey suppressed?
In storage. (Active in voiding).
What is the external urethral sphincter?
Skeletal muscle, voluntary sphincter.
Composed of the rhabosphincter and pelvic floor.
Do the urethral sphincters receive parasympathetic or sympathetic innervation?
Sympathetic.
When are the urethral sphincters activated?
In storage - activation causes contraction of the sphincters.
Spermatogenesis: what do type B cells differentiate into?
They differentiate into primary spermatocytes that will then go onto meiosis.
Spermatogenesis: where are type A cells located?
Outside the blood-testes-barrier.
Spermatogenesis: what does meiosis 1 produce?
2 secondary spermatocytes.
Spermatogenesis: what does meiosis 2 produce?
4 spermatids.
What changes does the sperm make with regards to its structure?
- It discards excess cytoplasm.
- Grows flagellum.
- Lots of mitochondria.
- Acrosomes at its head.
What is the function of the epididymis?
Storage and maturation of sperm. Sperm normally stay in the epididymis for 60 days.
What is the affect of FSH on the testes?
Stimulates spermatogenesis and sertoli cells. Sertoli cells produce MIF (mullerian inhibiting factor) and inhibin and activin which acts on the pituitary gland to regulate FSH.
What is the affect of LH on the testes?
Stimulates Leydig cells to produce testosterone.
What is ovulation?
The release of an oocyte from a follicle.
What hormone stimulates ovulation?
LH.
In humans, is the sex of the embryo determined by the sperm or egg?
The sperm - can contribute an X or Y. The egg is always X.
What is the secretory phase?
When the corpus luteum releases progesterone and the endometrium generates blood vessels and proteins etc needed for the implantation of a fertilised embryo.
What is the proliferative phase?
When the endometrium grows rapidly under the influence of oestrogen.
What does the corpus luteum degenerate into?
The corpus albicans.
What is capacitation?
The final stage of sperm maturation that occurs in the female genitalia. Before this spermatozoa would be unable to fertilise an oocyte.
What is block to polyspermy?
After a sperm has fertilised the egg, the egg needs to prevent further sperm fertilising it.
What are the mechanisms to ensure block to polyspermy?
Enzymes are released that harden the zona pellucida and inactivate sperm binding sites.
What hormone does the hypothalamus release that stimulates release of the gonadotropins?
GnRH - gonadotropin releasing hormone.
What cells does FSH act on in males?
Sertoli cells.
What cells does FSH act on in females?
Granulosa cells.
What cells does LH act on in males?
Leydig cells.
What cells does LH act on in females?
Theca cells.
What is the function of sertoli cells?
They release MIF, inhibin and activins (regulate FSH secretion), and androgen binding protein (increases testosterone concentration).
What is the function of granulosa cells?
They convert androgens into oestrogen using aromatase enzyme.
What is the function of leydig cells?
they produce testosterone.
What is the function of theca cells?
They produce androgens (oestrogen precursors) which diffuse into granulosa cells to form oestrogen.
What enzyme converts androgens into oestrogen?
Aromatase.
What is the predominant hormone responsible for the proliferative phase?
Oestrogen.
What is the predominant hormone responsible for the secretory phase?
Progesterone.
Where do primordial germ cells originate from in the embryo?
The epiblast.
Until what week are male and female primitive gonads identical?
Week 6.
What is the mesovarium?
Mesentery attaching the ovary to the posterior broad ligament.
Define menopause.
Cessation of menstruation.
What physiological changes happen in menopause?
There is depletion of the primordial follicles. Oestrogen levels decrease; FSH and LH therefore increase as they’re not inhibited by negative feedback.
What happens to oestrogen levels at menopause?
They fall.
What happens to LH and FSH levels at menopause?
They increase as they’re no longer inhibited by negative feedback.
What are the short-term symptoms of menopause?
Hot flushes, night sweats, palpitations, irritability, lethargy, decreased libido, vaginal dryness, vaginal pH change, dry skin and hair, brittle nails.
What are the long-term symptoms of menopause?
Osteoporosis and increased risk of cardiovascular disease.
Name 4 treatments that can help with the symptoms of menopause.
- HRT.
- Sedatives.
- Calcium supplements.
- Vitamin D supplements.
What hormones are given in HRT?
Oestrogen and progesterone.
What is the advantage of HRT being given as a patch as opposed to orally?
The hormones go straight into the bloodstream and so bypass the liver.
What are the risks of HRT?
Small increased risk of cervical, breast and endometrial cancer.
What are the two main types of stem cells?
- Embryonic stem cells - pluripotent.
- Somatic stem cells - multi-potent.
Name 3 diseases that stem cells could help to cure.
- Parkinsons disease.
- Alzheimers.
- Type 1 diabetes.
What are the 3 main characteristics of stem cells?
- Self renew over long periods.
- Undifferentiated.
- Can generate other cells: pluripotent/multipotent.
Where in the embryo do embryonic stem cells come from?
The inner cell mass.
What are the 3 histological layers of the uterus?
- Endometrium - mucosal lining, pseudostratified columnar.
- Myometrium - smooth muscle wall.
- Perimetrium.
What is the function of the smooth muscle in the myometrium?
It helps the uterus to expand and acts to protect the foetus. It also provides a mechanism for foetal expulsion.
What are the characteristics of the endometrium in the proliferative phase?
Straight glands, no secretions. Stromal and epithelial mitoses.
What are the characteristics of the endometrium in the early secretory phase?
Coiling of glands and subnuclear vacuoles
What is the decidua basalis?
A part of the endometrium invaded by trophoblast.
What is the decidua capsularis?
A part of the endometrium overlying the blastocyst.
What is the decidua parietalis?
Endometrium lining the rest of the uterine cavity.
What invades the decidua basalis?
Syncytiotrophoblast.
What is the role of the syncytiotrophoblast?
Uptake of oxygen and nutrients from the maternal blood.
Release of CO2 and waste products into the maternal blood. The exchange surface is gradually increased during maturation due to branching of the villi.
What is the role of the cytotrophoblast?
Forms solid masses covered by syncytiotrophoblast - primary chorionic villi. These masses become filled with stroma, forming secondary chorionic villi. Capillaries appear in the stroma – tertiary chorionic villi.
What hormonal pathway is likely to be responsible for a decrease in urine production?
Renin angiotensin aldosterone system.
Why is it important that the chorionic villi branch in maturation?
Branching increases the surface area for exchange of nutrients.
Why can a tumour of the pituitary gland affect vision?
The optic chiasm lies just above the pituitary gland and is likely to be affected if there’s a tumour.
What are the two types of hormone?
- Made at response e.g. steroids.
- Stored and released at response e.g. pituitary hormones (peptides).
Where are the receptors for steroid hormones located?
Steroid receptors are intracellular - steroids pass through plasma membranes bound to proteins.
Where are the receptors for peptide hormones located?
On cell membranes.
What are the purposes of the endocrine system?
- Communication between cells.
- Integrates whole body physiology.
- It can make rapid adaptive changes.
- Maintains the metabolic environment.
Briefly describe the mechanism of ACTH.
Hypothalamus -> CRH -> anterior pituitary -> ACTH -> adrenal glands -> cortisol release -> negative feedback on hypothalamus and pituitary.
Briefly describe the mechanism of LH and FSH.
Hypothalamus -> GnRH -> anterior pituitary -> FSH/LH -> sertoli cells, leydig cells/granulosa cells, theca cells -> oestrogen, testosterone, inhibin -> negative feedback on hypothalamus and pituitary.
How would you describe growth hormone secretion from the anterior pituitary?
It is secreted in a pulsatile fashion and increases during deep sleep.
What factors effect growth hormone secretion?
- Starvation.
- Exercise.
- Trauma.
- Hypoglaecemia.
- Deep sleep.
What clinical abnormalities can occur if there is a problem with growth hormone secretion?
- Gigantism.
- Dwarfism.
- Acromegaly.
What would be the effect on TSH if you had an under-active thyroid?
TSH would be high as there would be little negative feedback as less T4 and T3 are being produced.
What would a low TSH tell you about the action of the thyroid?
Low TSH = overactive thyroid.
Lots of T4 and T3 being produced and so there is more negative feedback on the pituitary and less TSH.
What are the 4 cells to make up the islets of langerhans?
- Beta cells: insulin. (70%)
- Alpha cells: glucagon. (20%)
- Delta cells: somatostatin. (8%)
- Pancreatic polypeptide secreting cells. (2%)
What is the importance of the alpha and beta cells being located next to each other in the islets of langerhans?
This enables them to ‘cross talk’ - insulin and glucagon show reciprocal action.
Insulin release is described as biphasic. Describe the two phases.
- Phase 1 - Stored insulin is released rapidly.
- Phase 2 - Slower release of newly synthesised insulin.
What is glucose converted into when it enters a beta cell?
Glucose-6-phosphate.
Describe the mechanism of insulin secretion from beta cells.
Glucose binds to beta cells -> glucose is converted into glucose-6-phosphate -> ADP is converted to ATP -> K+ channels close -> membrane depolarisation -> Ca2+ channels open -> Ca2+ influx -> insulin release.
What substance can tell you if high insulin levels are due to endogenous insulin production?
The presence of C peptide.
What glucose transporter allows glucose uptake into muscle and fat cells?
GLUT-4.
What is a normal blood glucose?
4-6mmol/mol.
What is the short term response to high blood glucose?
Glycogenesis.
What is the long term response to high blood glucose?
Triglyceride production - lipogenesis.
What is the short term response to low blood glucose?
Glycogenolysis.
What is the long term response to low blood glucose?
Gluconeogensis.
Name 3 places where glucose sensors are located.
- Pancreatic islets.
- Medulla.
- Hypothalamus.
What happens to insulin and glucose levels after a meal?
Insulin release increases. Glucose goes to the liver and muscles to replenish glycogen stores. Excess glucose is converted into fats.
What hormones from the hypothalamus stimulate the anterior pituitary to release GH?
GHRH (+ve affect) and SMS (-ve affect).
What can pituitary tumours cause?
- Pressure on local structures e.g. optic chiasm. Can result in bitemporal hemianopia.
- Pressure on normal pituitary function; hypopituitary.
- Functioning tumour can result in Cushing’s disease, gigantism and prolactinoma.
How much of the total cardiac output does each kidney receive?
10%.
What equation can be used to calculate GFR?
GFR = (Um x urine flow rate) / Pm.
- Um = concentration of marker substance (m) in urine.
- Pm = concentration of marker substance (m) in plasma.
What hormones are involved in pregnancy?
- Human chorionic gonadotropin.
- Oestrogen.
- Progesterone.
- Prolactin.
- Prostaglandins.
- Oxytocin.
- Relaxin.
What is the function of human chorionic gonadotropin?
It stimulates oestrogen and progesterone production. The levels of this hormone decrease when the placenta develops and takes over.
What are the functions of prostaglandins?
They have an important role in labor initiation.
What is the function of relaxin?
It is involved in cervical ripening.
What are the cardiovascular maternal adaptations?
- Cardiac output increases.
- Blood pressure decreases.
- Uterine blood flow increases.
Why does blood pressure decrease in pregnancy?
There is mass vasodilation which reduces the TPR and so BP decreases. (BP=TPRxCO).
Why does uterine blood flow increase in pregnancy?
To ensure enough nutrients are delivered to the foetus.
What are the adaptations to the skin in pregnancy?
Linea nigra and striae gravidarum/stretch marks may appear on the skin, usually the abdomen. There is also darkening of the areola
What are the maternal adaptations to the veins in pregnancy?
Varicose veins are often present in pregnancy.
Define parturition.
Giving birth.
What are the 3 layers of the uterus?
- Perimetrium (inner).
- Myometrium.
- Endometrium.
Describe cervical ripening.
Softening of the cervix that begins prior to labor. It is necessary for cervical dilation. It occurs under the influence of relaxin and placental hormones.
What hormones stimulate cervical ripening?
Relaxin and placental hormones.
What are the 2 main stages of labor?
- Latent: little cervical dilation.
- Active: cervix dilates and opens.
What are the sub-divisions of the active stage of labor?
1st - cervix dilation begins.
2nd - cervix is fully dilated and birth begins.
3rd - birth and expulsion of the placenta.
What hormones are needed for the initiation of labor?
Prostaglandins and oxytocin.
What is the function of PGF2 alpha?
It enhances oxytocin activation.
What does the adrenal medulla produce?
Adrenaline and noradrenaline (catecholamines).
What do steroid hormones bind to so they can be transported through the blood?
CBG proteins.
Why do steroid hormones bind to CBG proteins?
They are H2O insoluble and so need to bind to CBG for transport through the blood.
Where does the anterior pituitary gland originate from?
It is epithelial in origin. Derived from the primitive gut tube.
What happens to adrenal glands if there isn’t enough ACTH?
They will shrink.
What are glucocorticoids released in response to?
Stress!
What regulates secretion of adrenaline and noradrenaline?
Autonomic innervation, mainly sympathetic.
Where does the posterior pituitary gland originate from?
Originates from neuronal tissue.
What are the physiological functions of cortisol in response to stress?
- Mobilises energy sources: increases protein catabolism, lipolysis and gluconeogenesis. This help to maintain blood glucose levels.
- Enhanced vascular reactivity; maintains vasoconstriction with noradrenaline.
- Suppresses inflammatory and immune responses.
- Inhibition of non-essential functions e.g. growth and reproduction.
Why is there increased cortisol released in response to stress?
Stress poses a threat to homeostasis. Cortisol acts to maintain BP, provide extra energy sources and to shut down non-immune functions so homeostasis can be maintained.
Why is infertility a consequence of stress?
When someone is stressed, their cortisol levels increase, the extra cortisol acts to shut down non-essential functions such as reproduction and so can result in infertility.
What is the epithelium of the anal canal above the pectinate line?
Simple columnar.
What is the epithelium of the anal canal below the pectinate line?
Stratified squamous.
What are the functions of a normal bladder?
Continence, sensation of volume, receptibe relaxation. Voluntary initiation of voiding and complete emptying.
What is the bladder composed of?
Multiple segments of smooth muscle with their associated ganglia. Each segment exhibits
spontaneous activity - ‘micromotions’.
Can the bladder be denervated?
NO!
Which urethral sphincter is composed of skeletal muscle?
External urethral sphincter.
External urethral sphincter.
A visceral and somatic control centre for the lower urinary tract.
What fibre input does the periaqueductal grey receive?
A delta fibres.
What is urinary incontinence?
The involuntary release of urine.
Name 2 types of incontinence.
- Stress incontinence.
- Urge incontinence.
What can stress incontinence be due to?
Sneezing, coughing, exercise.
What can cause urge incontinence (desire to urinate)?
Any irritation to the bladder or urethra e.g. a bacterial infection.
How long does spermatogenesis take?
Approximately 60 days.
What forms the blood testes barrier?
Tight junctions between sertoli cells.
What is the function of the blood testes barrier?
It prevents the movement of cytotoxic agents from the blood into the lumen of the seminiferous tubules. This ensures proper conditions for germ cell development.
Describe the hypothalamo-pituitary-testicular-axis.
GnRh from hypothalamus acts on the anterior pituitary to release LH and FSH. LH acts on Leydig cells stimulating testosterone release. FSH acts on sertoli cells stimulating inhibin release. Inhibin and testosterone have a negative feedback affect on the hypothalamus and anterior pituitary.
What does semen contain?
Sperm, fructose, fibrinogen, clotting enzymes, fibrinolysin.
What is the importance of meiosis in gametogenesis?
It prevents polyploidy and increases genetic variability and so diversity.
How many secondary oocytes does each primary oocyte yield?
1 secondary oocyte and 1 non-functional polar body.
Why does each primary oocyte yield only one secondary oocyte?
Because only one ovum can be yielded per primary oocyte. The secondary oocyte divides into one ovum and a second polar body.
Describe the hormonal changes that occur at puberty.
- Increased amplitude of GnRH and GHRH.
- Increased levels of FSH, LH and sex steroids.
- Increased levels of growth hormone.
What factors can influence puberty?
- Nutrition (body mass).
- Leptin, insulin (hormones).
- Genetics.
- Exercise.
- Socio-cultural.
Describe the hypothalamo-pituitary-ovarian-axis?
GnRh from hypothalamus acts on the anterior pituitary to release LH and FSH. LH acts on theca cells stimulating androgen release. Androgen diffuses from theca to granulosa. FSH acts on granulosa cells stimulating the conversion of androgen into oestrogen (aromatase enzyme). Inhibin is also released from granulosa cells. Inhibin and oestrogen have a negative feedback affect on the hypothalamus and anterior pituitary.
What is the function of dihydrotestosterone?
Stimulates the differentiation of the male external genitalia. It is secreted by the testis.
Menstrual cycle: what is the effect of oestrogen at low levels on the gonadotropins?
Oestrogen is released from granulosa cells and also from the developing and dominant follicle.
Menstrual cycle: what is the effect of decreasing FSH levels in the follicular phase?
Decreasing FSH levels cause the non-dominant, immature follicles to degenerate.
Menstrual cycle: what is the effect of oestrogen at high levels on the gonadotropins?
At high levels oestrogen exerts a positive feedback on gonadotropin secretion, this stimulates the LH surge.
Menstrual cycle: what is the importance of the low LH concentration in the luteal phase?
Low but adequate LH acts to maintain the corpus luteum.
Menstrual cycle: what causes oestrogen and progesterone concentrations to fall towards the end of the luteal phase?
The corpus luteum degenerates into the corpus albicans if fertilisation does not occur. Therefore progesterone and oestrogen are no longer released.
Menstrual cycle: why do FSH levels increase at the end of the cycle?
The fall in progesterone and oestrogen concentration means FSH is no longer inhibited and so its plasma concentration begins to rise.
Menstrual cycle: why does the corpus luteum not degenerate if fertilisation occurs?
When the blastocyst implants the invading trophoblast cells release human chorionic gonadotropin (hCG). This acts to maintain the corpus luteum throughout pregnancy.
What is capacitation?
The final stage of sperm maturation that occurs inside the female reproductive tract. Before this stage the sperm would be unable to fuse with the egg.
Describe the mechanism of block to polyspermy.
- The egg releases contents of secretory vesicles by exocytosis.
- Enzymes from the vesicles enter the zona pellucida and inactivate sperm binding sites and harden the zona pellucida.
Describe implantation.
The blastocyst implants into the endometrium on day 6. The trophoblast cells overlying the ICM invade the endometrium. Nutrient rich endometrial cells provide the metabolic fuel for early embryo growth until the placenta takes over.
hCG stimulates oestrogen and progesterone levels to increase rapidly in pregnancy. What are their functions?
- Oestrogen: prepares the uterus and regulates progesterone levels.
- Progesterone: inhibits uterine contractility so the foetus is not delivered prematurely.
What is the effect on LH and FSH of high oestrogen and progesterone levels throughout pregnancy?
Inhibits LH and FSH and so prevents further menstrual cycle’s during pregnancy.
You have isolated a part of the nephron from the lumen of which large quantities of glucose and amino acids are re-entering the circulation. What part of the kidney are you studying?
Proximal convoluted tubule - bulk reabsorption occurs here.
Whilst looking at the lumen of the nephron you find some epithelial cells that flat rather than cuboidal. What part of the nephron are you looking at?
The thin limb of the loop of henle - flat epithelium.
What is the epithelium of the thick limb of the loop of henle?
Columnar epithelium. Structurally similar to the PCT and DCT.
What are tubulopathies?
Mutations of apical sodium transporters.
Where in the nephron would be affected by Bartters syndrome?
The loop of Henle.
What channels are affected in Bartters syndrome?
NKCC2 channels in the loop of Henle.
What is the diuretic equivalent to Bartters syndrome?
Loop diuretics.
What are the features of Bartters syndrome?
Hypokalemia, low blood pressure, alkalosis.
What channels do loop diuretics close?
NKCC2 - reduced Na+ and K+ secretion.
What part of the nephron would be affected by Gitelmans syndrome?
The distal tubule.
What channels are affected in Gitelmans syndrome?
NCC.
What is the diuretic equivalent to Gitelmans syndrome?
Thiazide.
What are the features of Gitelmans syndrome?
Hypokalemia, hypomagnesemia and low blood pressure.
What part of the nephron would be affected by Liddles syndrome?
The collecting duct.
What channels are affect in Liddles syndrome?
ENaC.
What are the features of Liddles syndrome?
Hypertension and Hypokalemia.
What atom is crucial in thyroid hormone formation?
Iodine.
What cells in the thyroid actively take up iodine in the form of iodide?
Follicular cells.
What process needs to occur before T3 and T4 can be released into the blood stream?
Proteolysis.
Is more T4 or T3 produced in the thyroid?
T4 (thyroxine).
Which molecule is active T3 or T4?
T3 (triiodothyronine).
More T4 is produced than T3 in the thyroid. What process produces T3 elsewhere?
As T3 is more active it can be produced peripherally from the conversion of T4.
Describe the GH/IGF-1 axis.
Hypothalamus -> GHRH (+) or SMS (-) -> anterior pituitary -> GH -> Liver -> IGF-1 -> negative feedback on hypothalamus.
What is the function of IGF-1?
It induces cell division.
What is the decidual reaction?
Following implantation of the blastocyst there is differentiation of endometrial cells adjacent to the blastocyst: decidual basalis (cells invaded by syncytiotrophoblast), decidua capsularis (cells overlying blastocyst), decidua parietalis (cells lining the rest of the uterine cavity).
What hormones increase in parturition?
Prostaglandins (initiation of labour) and oxytocin (uterine contractions).
What does the inguinal canal transmit in females?
The round ligament of the uterus.
What is the function of the round ligament of the uterus?
Maintains the anteverted position of the uterus.
Give 2 reasons why the pH of the skin needs to be maintained at about 5.5.
- The low pH switches on protease inhibitors that prevents corneodesmosome breakdown.
- The low pH also stimulates lipid processing. Lipids prevent H2O loss.
What is the anion gap?
The difference between measured cations and anions: [Na+] + [K+] - [Cl-] - [HCO3-]
What pituitary hormone can cause hyperpigmentation?
ACTH.
Give 2 tests that can be used to screen for disorders in pregnancy.
- Ultrasound.
- Amniocentesis.
What is the most abundant glucocorticoid in humans?
Cortisol.
Name the effect cortisol has on three other hormones.
- Adrenaline - up-regulates beta2 receptors therefore potentiates adrenaline.
- Insulin - inhibits. Cortisol acts to increase blood glucose.
- Glucagon - activates. Cortisol acts to increase blood glucose.
What hormone causes production of sperm?
FSH.
In what specific cell in the testes do sperm mature?
Sertoli.
Name 2 hormones that regulate melanin secretion.
- ACTH.
- MSH.
Give 6 functions of the skin.
- Barrier to infection.
- Protection against trauma.
- Protection against UV.
- Thermoregulation.
- Vitamin D synthesis.
- Waterproof.
What organelle stores melanin in melanocytes?
Melanosomes.
Give 3 histological characteristics of the secretory phase.
- Spiral arteries.
- Decidualised stroma.
- Secretions.
- Torturous glands.
What type of receptor does ACTH act on?
G protein coupled receptor. (All pituitary and hypothalamus hormones act on these receptors).
What hormone acts on the uterus in the proliferative phase?
Oestrogen.
What changes happen to the endometrium in the proliferative phase?
Growth of the endometrium and myometrium is stimulated. Receptors for progesterone are also stimulated.
What hormone acts on the uterus in the secretory phase?
Progesterone.
What changes happen to the endometrium in the secretory phase?
It becomes a secretory tissue: endometrial glands are coiled and filled with glycogen, blood vessels become more numerous and spiralled. Progesterone also inhibits myometrial contractions to ensure that
a fertilized egg can safely implant once it arrives in the uterus.
What are the histological characteristics of the endometrium in the mid-secretory phase?
Tortuous glands, vacuoles above and below the nucleus, stroma-oedema and secretions.
What are the histological characteristics of the endometrium in the late-secretory phase?
Prominent spiral arteries and decidualised stroma. More secretions and elongated glands.
What effects does oestrogen have on the endometrium?
Hyperplasia and hypertrophy of endometrial cells. Also stimulates myometrial growth.
Name one hormone from the pituitary gland one from the chorion/decidua that induces labour.
Pituitary – oxytocin.
Decidua/chorion – prostaglandins.
What do the macula densa cells release when they detect low NaCl?
Prostaglandins.
Prostaglandins act on granular cells and trigger renin release.
What enzyme is found only in the zone glomerulosa?
Aldosterone synthase.
What 2 structures make up the metanephros?
- Metanephric blastema.
- Ureteric bud.
What is dihydrotestosterone?
An active metabolite of testosterone. It modulates external genitalia differentiation -> penis, scrotum and prostate.
What is the ureteric bud an outgrowth of?
The mesonephric duct.
What are the start and end products of mitosis in oogenesis?
Start: oogonia.
End: primary oocyte.
What are the start and end products of meiosis in oogenesis?
Start: primary oocyte.
Middle: secondary oocyte.
End: 1x ovum.
Define tubulopathies.
Mutations of apical Na+ transporters.
What part of the nephron is affected by Bartter’s syndrome?
The loop of henle.
What channels are affected by Bartter’s syndrome?
NKCC2.
What is the diuretic equivalent to Bartter’s syndrome?
Loop diuretics.
What are the characteristic features of Bartter’s syndrome?
Hypokalemia, low BP, alkalosis.
What part of the nephron is affected by Gitelman’s syndrome?
The DCT.
What channels are affected by Gitelman’s syndrome?
NCC.
Name 2 hormones that are produced elsewhere but are activated in the kidney.
- Angiotensinogen.
- 25-hydroxyvitamin D.
What are the 6 stages of implantation?
- Apposition.
- Attachment.
- Differentiation of trophoblast.
- Invasion of endometrium.
- Decidual reaction.
- Maternal recognition.
What are C-cells also known as?
Parafollicular cells.
What amino acid and dietary nutrient are needed for hormones to be secreted from the thyroid gland?
Amino acid - tyrosine.
Dietary nutrient - iodine.
Name 2 proteins in the blood that hormones from the thyroid gland bind to?
- Albumin.
- Thyroxine binding globulin.
Name 2 prostaglandins released in labour.
- PGE2.
- PGF2-alpha (main one).
Give 3 functions of the placenta.
- Provides nutrition to the foetus.
- Gas exchange.
- Waste removal.
- Endocrine and immune support.
Placental abnormalities often require caesarian delivery. What is placenta accreta?
Abnormal adherence, no decidua basalis.
Placental abnormalities often require caesarian delivery. What is placenta perceta?
Where the villi penetrate the myometrium.
Placental abnormalities often require caesarian delivery. What is placenta praeria?
The placenta overlies the internal os, there is abnormal bleeding.
What 2 hormones are secreted in the kidney?
EPO and renin.
Give 2 causes of metabolic acidosis.
Ketoacidosis and lactic acidosis.
What hormones do acidophils in the anterior pituitary secrete?
GH and prolactin (Somatotrophs and lactotrophs).
What hormones do basophils in the anterior pituitary secrete?
FSH, LH, TSH and ACTH. (Corticotrophs, thyrotrophs and gonadotrophs).
Give an example of a steroid hormone.
Oestrogen, testosterone, cortisol.
Give an example of a peptide hormone.
Insulin, GH, FSH, LH, TSH etc.
Which has a faster response, steroid or peptide hormones?
Peptide hormones have a rapid response.
Which is stored, steroid or peptide hormones?
Peptide hormones are stored.
Importance of hormones during pregnancy
- Maintains pregnancy
- Prepares for delivery
- Prepares for breast feeding e.t.c
Important hormones involved in pregnancy
- B-hCG
- Oestrogen
- Progesterone
What produces B-hCG
Placenta
Physiological changes during pregnancy
Respiratory :
Increase in Intraabdominal pressure.
Increase in tidal volume
More diaphragmatic breathing
Cardiovascular:
Increase CO
Decrease in systemic vascular resistance → Increase SV
Drop-in B.P
Haematological:
Increase in plasma volume (40%)
Increase in red blood cell volume
Increase in clotting factors
MSK:
Increase in BMI
Stretch marks
Lower back pain
Endocrine:
Increase anterior pituitary gland secretion
Pregnancy hormone: Oestrogen, Progesterone, B-hCG
Thyroid
Dermatological
Increase in skin pigmentation
Distension + proliferation of blood vessels
Deficiences developed during pregnancy
Anaemia
Gestational diabetes
Pituitary gland position
Hanging off hypothalamus connected to the infundibulum
Nuclei found in the posterior pituitary gland
Supraoptic nucleus
Paraventricular nucleus
What does the supraoptic nucleus secrete?
ADH/ Vasopressin
What stimulates the supraoptic nucleus in the hypothalamus
low blood volume
low blood pressure
high plasma osmolality
pain
What effect does alcohol have on the supraoptic nucleus
Inhibitory
What does the paraventricular nucleus secrete in the posterior pituitary gland
Oxytocin
What stimulates the paraventricular nucleus in the posterior hypothalmus
Birthing process
Suckling
Ejaculation
What is the hypophyseal portal system
2 capillary beds (primary & secondary capillary plexuses)
Connected in series through an intermediate portal vein
this is the anterior pituitary connection
The paraventricular nucleus secretes what in the anterior compartment of the pituitary gland
CRH: Corticotropin-releasing hormone
TRH: Thyrotropin-releasing hormone
Action of CRH
Stimulates genes in corticotrope.
Proopiomelanocortin gets broken down into Alpha Milano stimulating hormone (alpha MSH) and adrenocorticotropic hormone (ACTH)
Action of TRH
Stimulates thyrotrope to release TSH
What does the arcuate nucleus secrete
Growth Hormone releasing hormone
PIH or dopamine
The action of Growth Hormone releasing hormone
Causes stimulation of somatotrope to secrete growth hormone
The action of PIH or dopamine
Stimulates lactotrope to secrete Prolactin
Ganado tropen releasing hormone action
Stimulates Gonadotrope to secrete FSH LH
Depending on the frequency of GnRH: High frequency is LH, lower frequency is FSH
Somatostatin inhibits this
Nucleus present in anterior pituitary gland
Paraventricular nucleus
Arcuate nucleus
Preoptic nucleus
What does oxytocin bind to in the uterus?
smooth muscle of the myometrium
causing it to contract and therefore help during birthing process
Oxytocins involvement in lactation
Binds to the mammillary bodies of breasts send signals to the hypothalamus
Results in milk ejection during lactation
Stimulated by suckling
Oxytocin has a ____ half life
short
so regulated frequnetly
What receptor does ADH bind to the principal cell of the collecting tube
What receptor does ADH bind to in blood vessels
Vasopressin type 2 receptor
Vasopressin type 1 receptor
Steps of ADH activation
Stimulus sends receptors to the hypothalamus
The supraoptic nucleus causes ADH to be secreted
Binds to V2 receptors
Stimulates Gs protein which binds to GTP and gets activated
This then binds to adenyl cyclase and converts ATP into cAMP activating pKa
pKa then goes and inserts into vesicles containing aquaporin 2 into the apical membrane
increases H20 Permeability of collecting duct
Effects of stimulation of ADH
Stimulated by low blood pressure or high plasma osmolality
In blood vessels: Increase vasoconstriction and therefore peripheral resistance and therefore increase blood pressure
In kidneys: Causes the increase of plasma volume and therefore BP
Hormones of the anterior pituitary gland
FLAT PIG
FSH
LH
ACTH
TSH
Prolactin
GH
What nucleus secrete growth hormone
Arcuate nucleus
What inhibits/ stimulates prolactin
inhibits PIH or dopamine (arcuate nucleus)
stimulates: thyrotropin-releasing hormone (paraventricular nucleus)
Stimulates: oestrogen + breastfeeding
How does iodide enter from the blood into follicles of the thyroid gland
secondary active transport
What does thyroid peroxidase do?
Iodide oxidation: turns iodide ions into iodine
Iodination: puts I2 onto amino acids on tyrosine amino acids
Fuses DIT + DIT = T4 (Throxine)
Fuses MIT + DIT = triodothyronin
What is it called when a tyrosine amino acid has:
one iodide group
two iodide group
Monoiodotyrosine
Diiodotyrosine
What makes up the thyroid hormone?
T4 thyroxine +
T3 triiodothyronine
How is T3 + T4 made from tyrosine molecule
Tyrosine is broken down into T3 + T4 components via lysozyme enzymes
Thyroid synthesis steps
- TRH release from paraventricular nucleus from hypothalamus
- Anterior pituitary to release from TSH
- TSH stimulates follicle cells of the thyroid to synthesise thyroglobulin
- Iodide trapping
- Oxidation of iodide via thyroid peroxidase
- Iodination of tyrosine amino acids
- Couple of the DIT + MIT
- Endocytosis of thyroglobulin with T3 + T4
- Lysosomal enzymes cleave T3 + T4 out of thyroglobulin
- Exocytosis of T3 + T4 into blood plasma
How does T3 act
Inducing gene transcription and protein synthesis
What does the Thyroid hormone do?
Promotes normal bone growth + maturation
Promotes muscular function and development
Increase basal metabolic rate/ O2 usage
Promotes normal C.O
Promotes an increase in synapses/myelinations/dendrites
Promotes G.I motility + secretions
Promotes normal hydration of skin
What cell is stimulated by low calcium levels
Chief cells
What does it mean when there is low blood calcium
Stimulates the parathyroid to secrete parathyroid hormone
How does the Parathyroid hormone affect kidneys
Increases calcium reabsorption decreasing Ca2+ excretion
Excreting phosphates as well
The indirect effect of the parathyroid hormone
- When exposed to sunlight 7 dehydrocholesterol gets drawn into the blood and broken down into Cholecalciferol
- Goes into the liver to become 25-OH Cholecalciferol
- Parathyroid hormone stimulates an enzyme in the kidney which together with 25OH cholecalciferol becomes 1,25 diOH Cholecalciferol (calcitriol)
- Calcitriol is the active form of vitamin D
What makes up the adrenal cortex
Zona glomerulosa
Zona Fasiculata
Zona Reticularis
What stimulates the adrenal cortex
Angiotensin 2 (1st)
low Na+ or high K+ (2nd)
ACTH (3rd)
Both undergo GS protein mechanism e.t.c to produce pKa which phosphorylates cholesterol conversion of ….
What is aldosterone derived from and what type of hormone is it?
Cholesterol
Steroid hormone
What inhibits Zona glomerulosa
Atrial natriuretic peptide
What hormones are corticosteroids
steroid hormones produced in the adrenal cortex
Cholesterol is the Precursor
What does aldosterone do?
Increase Na+ absorption
Decrease K+
Increase H2O absorption
Where is aldosterone produced
Zona glomerulosa
Where is cortisol secreted
Zona fasciculata
What stimulates Cortisol secretion
ACTH
undergoes same action as with aldosterone
What is cortisol derived from?
cholesterol
Steroid hormones transported around blood
Steroid hormones need carrier proteins to travel within the blood
What does zona glomerulosa secrete
Mineral corticoids (Aldosterone)
What does zona fasiculata secrete
Glucocorticoids (Cortisol)
What does zona reticulosa secrete
Gonadocorticoids (Androgens)
What stimulates zona fasiculata
What does cortisol do
Protein catabolism
Suppresses immune system
Lipolysis
Gonadocorticoids are …
weak
Adrenogens act on
Weak and therefore act as precursor
Fmelaes to release oestrogen
Males release testosterone
Libido effect
What feedback system does cortisol induce
Negative feedback system
Primary stimulant for sympathetic nervous system
Short term acute stress
Fight or flight
What contains sympathetic nerve fibers
Ventral grey horn of the spinal cord
What do chromaffin cells of the adrenal cortex convert tyrosine into
Epinephrine (80%)
Norepinephrine (20%)
What does epinephrine do once secreted by the adrenal cortex
Binds to the liver and through Gs protein… results in glycogenolysis and gluconeogenesis increasing glucose in blood
Increases BP and lypolysis
What is a heterocrine gland and given example
Has both endocrine and exocrine function
Pancreas
What cells do the endocrine portion of the pancreas have (Islets of Langerhans)
Alpha cell-glucagon
Beta cells-Insulin
What is beta pancreatic cells stimulus
Hyperglycaemia
What stimulates alpha pancreatic cells
Hypoglycaemia
Sympathetic nervous system
What does the exocrine portion of the pancreas have
Acini 99%
Where are insulin contained in the beta cell of the pancreas
Vesicles
C peptide is also within the vesicles
How is insulin produced
You have proinsulin undergoes cleaving processes in the RER modifications resulting in them being packaged in vesicles
Hyperglycaemia means that glucose enters through beta cells and gets broken down into ATP
Causes Vesicles to exocytose
What is C peptide
A good way to monitor insulin levels
What does insulin do?
The liver:
Promotes glycogenesis (Decrease glucose) and minor effect on protein synthesis
Increase amino acid uptake
Adipose tissue:
Stimulated lipogenesis
Increase glucose uptake via GLUT 4 = decrease blood glucose
Muscle:
Increase glucose uptake via Glut 4. A minor effect is glycogenesis
Increase amino acid uptake + protein synthesis
What does the endocrine portion of the pancreas have
Islets of Langerhans 1%
What does pancreatic alpha cell secrete
Glucagon
What does glucagon do?
In liver:
gluconeogenesis & glycogenolysis + to increase blood glucose levels
In adipose tissue:
Lipolysis
What is oogonium
Stem cells (dipolid)
What happens prepuberty
oogonium ⇢ primordial follicle (2n) stuck in prophase 1
Primary oocyte is…
Primordial follicle → Late secondary oocyte
What phase is graffian cells stuck in
Metaphase 2
What cells is primordial follicle stuck in
Prophase 1
Follicular phase
Primordial follicle → graffian cell
Follicular phase products
Mitosis
Oestrogen is produced
Follicular fluid
primary oocyte → secondary oocyte
What days does the follicular phase take place
1-14 days
What day of ovulation is peak oestrogen levels
day 14 (end of the follicular phase)
There is also a high amount of oestrogen in the mid follicular phase. This inhibits FSH and stimulates LH.
What happens at end of the follicular phase
Oestrogen stimulates GnRH to secrete LH and inhibits FSH (LH surge)
What does LH surge do?
increase follicular fluid (blood flow to antrum)
Stimulates graffian cells to release secondary oocyte- ovulation day 14-15
The secondary oocyte is caught by fimbriae and stays in the ampulla
What is the ovulatory phase
LH surge
How is the corpus luteum formed?
LH stimulates Remaining granulosa cells from ovulation to specialise
LH stimulates the corpus luteum to produce progesterone
What arteries are there within endometrium
Stratum functionalis: Spiral and Coil arteries
Stratum Basalis : Striaght arteries
Why is there blood during the menstruation phase
As the stratum Functionalis is being shed the spiral and straight arteries are also being shed.
Proliferation phase of menstrual cycle
regenration of stratum functionalis
regenerate spiral and coiled arteries
makes uterine glands
thin cervical mucous production
oestrogen is the primary hormone
Days 6-14
Secretory phase
The main hormone is progesterone
Angiogenesis
Secretion of uterine glands
Thickening cervical plug
Day 15-28
Where is spermatogenisis occuring
Seminiferous tubu`les
Where is spermatogenisis occuring
Seminiferous tubu`les
What cells make up seminiferous tubes
Sertoli cells
they are connected to one another via tight junctions/adherens junctions
What is the importance of tight junctions within seminiferous tubules
Splits into two compartments the basal compartment and the ad lumen compartment
Creates a barrier from preventing sperm antigens from entering bloodstream and therefore immune response- called the blood testes barrier
What does a spermatogonium split into? (2n)
Undergoes mitosis to become type A cell and type B cell
They type A cell continues to become reused is the next spermatogonium
Type B cell goes to ad luminal compartment (tight junctions open up)
When does a type B cell become a spermatocyte
When it gets past tight junctions and goes from basal lumen to ad luminal compartment
How are secondary spermatocyte made?
The primary spermatocyte undergoes meiosis 1 to become 2 secondary spermatocyte
This further undergoes meiosis 2 to become spermatids
Spermatids become _____ via _____
Spermatozoa via spermiogenesis
Spermatogenesis
What cell do LH act on for spermatogenesis on the actions does it do
Leydig cells they convert cholesterol into testosterone
What cell do FSH act on for spermatogenesis on the actions does it do
Acts on Sertoli cells to produce Androgen Bonding protein (ABG)
What two molecules are needed for spermatogenesis
testosterone and Androgen Bonding protein (ABG)
What is the role of androgen bonding protein
Helps keep testosterone very soluble and highly concentrated
What process do Sertoli cells primarily help with
Spermiogenesis
What kind of feedback system does a high testosterone levels initiate
Negative feedback system
What hormone is secreted by Sertoli cells when sperm levels are too high
Inhibin causes a negative feedback system with hypothalamus and anterior pituitary
Summary of the path of sperm to outside
S-Seminiferous tubules
R- Rete testis
E- Efferent duct
E- Epipdyms
V- Vas deferens
E- Ejaculatory duct
N- Nothing
U-Urethra
P- Penile Urethra
SREEVEN UP
Seminal vesicles
Accounts for 60-70% of seminal fluid
Fructose
Prostaglandin
Coagulase
Prostate gland
Accounts for 30% of seminal fluid
Citrate
Fibrinolysis
PSA
Role of prostaglandin in fertilisation
binds to the smooth muscle of the uterus and causes it to contract- retropulsion
Role of coagulase in fertilisation
Allows for sperm to bind to vagina wall
Stages of fertilisation
- Capacitation: cleaning of the sperm head. by the end it only has modified glycoproteins on its head. Increases mobility of sperm
- Acrosomal reaction: sperm binds with the ZP3 receptor. Calcium rushes in and activates the acrosome releasing its contents. Digests zona pellucida
- Fast block to polyspermy: sperm touches oocyte membrane beta unit of protein allows sodium in inhibiting other sperms from attaching
- Slow Block to Polyspermy: Alpha unit of protein causes the smooth endoplasmic reticulum releases Ca++ and activates lysozyme to fuse with the oocyte membrane. ZP3 degrades and hardens the zona pellucida. Sperm can no longer bind to the ZP3 receptor.
- Secondary oocyte undergoes meiosis Pronucleus of male and female fuse together
How many phases can the menstrual cycle be subdivided into?
Follicular phase (0-14)
Luteal Phase (14-28)
What happens in the follicular phase of the menstrual cycle
FSH will enter the ovaries and stimulate follicle maturation of primary follicles and mature follicles into a secondary follicle.
Oestrogen is produced during this phase
As oestrogen levels are rising to have positive feedback from LH. More LH is is secreted (LH surge= ovulation)
Oocyte is released
What kind of feedback does oestrogen have on the pituitary gland 10 days before the menstrual cycle begins
Negative and therefore inhibiting LH
In low concentration oestrogen inhibits …
LH secretion
When is FSH released? What is it in response to?
Low oestrogen conc
Roles of oestrogen
Stimulate bone and growth
Muscle growth
Stimulation of endometrial growth
Maintain female secondary characteristics
In high concentrations oestrogen stimulates
LH
Why is there an FSH surge alongside an LH surge
As a side effect of LH
What hormones does the corpus luteum secrete
Oestrogen
Inhibin
Progesterone
Luteal phase
Days 15-28
Progesterone is increasing
Oestrogen is still detectable, just in smaller amounts.
This suppresses GnRH release
Inhibin is increasing
Progesterone (+ oestrogen) stimulate endometrium growth
What feedback system does inhibin have
As the corpus luteum develops inhibin suppresses GnRH secretion
What happens to the corpus luteum during the luteal phase
The corpus luteum will degrade and therefore the hormones it secretes will decrease alongside it. It allows for other oocytes to mature.
Ovulation graph
Spermatogenesis vs spermiogenesis
Spermiogenesis: spermatid → spermatozoon. The maturation of a spermatid leads to the formation of a Sperm cell (spermatozoon). This takes place within Sertoli cells
Spermatogenis: Fomration of spermatozoa. Spermatogonium → 4 spermatozoa
