Flashcards in SUGER Deck (424):
Name the 3 things to make up the Glomerular Filtration barrier.
1. Fenestrated capillary endothelium.
2. Double layer basement membrane.
3. Foot processes of podocytes.
Name 5 factors that determine a molecule crossing the filtration barrier.
2. Size of the molecule.
3. Charge of the molecule (negative molecules are repelled).
4. Rate of blood flow.
5. Binding to plasma proteins.
What force favours glomerular filtration?
Hydrostatic pressure of the glomerular capsule.
Name 2 forces that oppose glomerular filtration.
1. Hydrostatic pressure of the bowman's space.
2. 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 is the definition of glomerular filtration rate?
The volume of fluid filtered from the glomeruli into Bowman's space per unit time.
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.
Name 2 ways in which GFR is regulated.
2. Tubuloglomerular feedback.
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.
What would happen if Nacl levels reaching the macula densa cells were very high?
The macula densa cells would signal to the afferent arterioles to vasoconstrict therefore reducing GFR.
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.
1. Freely filtered.
2. Not metabolised.
3. Not reabsorbed or secreted.
What substance can be used clinically to estimate GFR?
What is the usual value of the filtration fraction.
Define renal clearance.
Volume of plasma from which a substance is completely removed by the kidney per unit time.
Name 7 molecules that are reabsorbed in the proximal convoluted tubule.
Na+, K+, Cl-, HCO3-, H2O, amino acids, glucose.
Is the ascending or descending limb of the loop of henle permeable to H2O?
What is the purpose of countercurrent multiplication?
To generate a hypertonic medullary interstitium so H2O can be drawn out of the tubules and reabsorbed.
What ion is pumped out of the ascending limb into the medullary interstitium?
Na+. This increases the medullary osmolarity.
What are the 2 cell types found in the collecting duct.
Principal and intercalated.
What are the 4 main layers of the epidermis of the skin?
1. Keratinised squames.
2. Granular layer.
3. Spinous layer (the thickest layer).
4. 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?
How much H2O do we intake in a day?
How much salt do we intake in a day?
What is the equation for plasma osmolality?
2(Na + K) + glucose + urea
How is tonicity regulated?
By controlling H20 movement.
Is ADH a vasoconstrictor or a vasodilator?
Briefly describe ADH action.
1. Osmoreceptors in the hypothalamus detect an increase in plasma osmolality.
2. The posterior pituitary is signalled to release ADH.
3. ADH acts on the collecting ducts and increases insertion of aquaporin 2 channels, permeability to H2O increases, more H2O is retained.
How is fluid volume regulated?
By controlling Na+ movement.
List the 3 main triggers for the release of Renin.
1. Sympathetic stimulation.
2. Low BP detected by afferent arteriole.
3. Low Na+ detected by macula densa cells.
What is the function of ACE?
Converts angiotensin 1 into angiotensin 2.
Where is aldosterone synthesised?
In the adrenal cortex by glomerulosa cells.
Where does aldosterone act?
On the principal cells in the nephron collecting duct.
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?
What channels do Thiazides target?
Name 3 types of drugs you could give to someone with hypertension.
3. ACE inhibitors.
Name 3 urinary buffers.
2. Phosphate (commonest urinary buffer).
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 layer of the trilaminar disc are the kidneys derived?
What are the names of the 3 paired kidneys that develop in the embryo?
What does the mesonephros form?
The mesonephric ridge and duct.
What does the mesonephric duct form in the male?
The epididymis, vas deferens, seminal vesicles and ejaculatory duct.
What does the ureteric bud form?
The ureters, collecting duct, major and minor calyces and the renal pelvis.
What does the Müllerian duct form in females?
The uterine tubes, uterus, cervix and proximal 1/3 of vagina.
What is the cloaca divided into?
1. Anorectal canal.
2. Urogenital sinus.
What are the 3 parts of the urogenital sinus?
1. Upper part.
2. Pelvic part.
3. Phalic part.
What part of the urogenital sinus is the bladder formed from?
The upper part.
What does the pelvic part of the urogenital sinus form?
The prostatic and membranous urethra.
What does the phalic part of the urogenital sinus form?
The penile urethra.
What part of the trilaminar disc are the bladder and urethra formed?
What layer of the trilaminar disc forms the male and female genitalia?
What is the indifferent stage?
When the Wolffian and Müllerian ducts are both present. It is impossible to tell the sex of the embryo.
When are embryos no longer indifferent?
They are indifferent until the end of the 6th week.
What causes the genital ridge to form ovarian tissue?
This happens by default due to the lack of a gonadal hormone influence. There is no Y chromosome and so no sex determining region and so no testis determining factor released.
Why does the mesonephric duct degenerate in a female?
Due to the absence of testosterone.
What does oestrogen stimulate?
The development of the female external genitalia and the differentiation of the Müllerian duct.
What does the female external genitalia develop from?
The urogenital sinus.
What does the urethral fold form in a female?
The labia minora.
What does the genital tubercle form in a female?
What does the genital swelling form in a female?
The labia majora.
True or False: the ovary lies behind the broad ligament.
What is the fornix?
The space between the cervix and the vagina.
What is the hymen formed from?
The urogenital sinus.
What is the primitive streak?
A depression in the epiblast.
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.
When do leydig cells start producing testosterone?
What does testosterone stimulate?
Differentiation of the Wolffian duct.
Why does the Müllerian duct degenerate?
Due to inhibiting substance being released from sertoli cells.
What forms from degeneration of the Müllerian duct?
What forms the phallus?
Elongation of the genital tubercle.
What does the genital swelling form in a male?
What is meckle's diverticulum a remnant of?
The vitelline duct - connected the midgut to the yolk sac.
What is the significance of the Hilton white line?
It separates the non keratinised and keratinised epithelium in the anal canal.
When does the anal membrane rupture?
In the 7th week. This allows the upper 2/3 to be continuous with the lower 1/3 of the anal canal.
What layer of the trilaminar disc is the upper 2/3 of the anal canal derived from?
What layer of the trilaminar disc is the lower 1/3 of the anal canal derived from?
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?
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 is the function of type A cells?
They replicate by mitosis to ensure a constant supply of spermatogonia to fuel spermatogenesis.
Spermatogenesis: what does meiosis 1 produce?
2 secondary spermatocytes.
Spermatogenesis: what does meiosis 2 produce?
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 collects sperm from the rete testis and transfers it to the epididymis?
The efferent ductules.
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?
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 is the function of GnRH?
It acts on the anterior pituitary gland stimulating it to release FSH and LH.
What cells does FSH act on in males?
What cells does FSH act on in females?
What cells does LH act on in males?
What cells does LH act on in females?
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?
What is the predominant hormone responsible for the proliferative phase?
What is the predominant hormone responsible for the secretory phase?
Where do primordial germ cells originate from in the embryo?
Until what week are male and female primitive gonads identical?
What is the mesovarium?
Mesentery attaching the ovary to the posterior broad ligament.
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?
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.
3. Calcium supplements.
4. 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?
1. Embryonic stem cells - pluripotent.
2. Somatic stem cells - multi-potent.
Name 3 diseases that stem cells could help to cure.
1. Parkinsons disease.
3. Type 1 diabetes.
What are the 3 main characteristics of stem cells?
1. Self renew over long periods.
3. 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?
1. Endometrium - mucosal lining, pseudostratified columnar.
2. Myometrium - smooth muscle wall.
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?
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.
Why is it important that the chorionic villi branch in maturation?
Branching increases the surface area for exchange of nutrients.
What hormonal pathway is likely to be responsible for a decrease in urine production?
Renin angiotensin aldosterone system.
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.
Name 6 hormones produced by the anterior pituitary gland.
Name 2 hormones produced by the posterior pituitary gland.
How does the anterior pituitary gland receive its blood supply?
Via a portal venous circulation from the hypothalamus.
What are the two types of hormone?
1. Made at response e.g. steroids.
2. 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?
1. Communication between cells.
2. Integrates whole body physiology.
3. It can make rapid adaptive changes.
4. Maintains the metabolic environment.
Describe the thyroid axis.
Hypothalamus releases TRH -> anterior pituitary is stimulated to release TSH -> thyroid -> thyroxine (T4) -> T3 production -> T4 and T3 have a negative feedback effect on the hypothalamus and pituitary.
What does thyroid hormone affect?
Increased metabolism, increased sympathetic action, heat production, essential for growth and development too.
What effect does prolactin have on dopamine?
It increases dopamine levels - positive feedback effect.
Briefly describe the mechanism of prolactin.
Hypothalamus -> dopamine -> anterior pituitary -> prolactin -> mammary glands -> milk production -> positive feedback on dopamine.
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?
5. Deep sleep.
What clinical abnormalities can occur if there is a problem with growth hormone secretion?
What does the parathyroid control?
Serum Ca2+. (Hyperparathyroidism -> hypercalcemia).
What hormone does the parathyroid secrete and what is its function?
PTH - it increases the absorption of Ca2+ and is secreted when Ca2+ levels fall.
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?
1. Beta cells: insulin. (70%)
2. Alpha cells: glucagon. (20%)
3. Delta cells: somatostatin. (8%)
4. 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.
What is the function of insulin?
1. Suppresses hepatic glucose output: decreases glycogenolysis and gluconeogensis.
2. Increases glucose uptake into fat and muscle cells.
3. Suppresses lipolysis and muscle breakdown.
What is the function of glucagon?
1. Stimulates hepatic glucose output: increases glycogenolysis and gluconeogenesis.
2. Reduces peripheral glucose uptake.
3. Stimulates release of gluconeogenic precursors.
4. Stimulates lipolysis and muscle breakdown.
Insulin release is described as biphasic. Describe the two phases.
1. Phase 1 - Stored insulin is released rapidly.
2. Phase 2 - Slower release of newly synthesised insulin.
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 is glucose converted into when it enters a beta cell?
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?
Describe insulin action at muscle and fat cells.
Insulin binds to membrane receptors -> intracellular signalling cascade stimulated -> GLUT-4 mobilisation to plasma membrane -> GLUT-4 integrates into plasma membrane -> glucose enters cell via GLUT-4.
What is a normal blood glucose?
What is the short term response to high blood glucose?
What is the long term response to high blood glucose?
Triglyceride production - lipogenesis.
What is the short term response to low blood glucose?
What is the long term response to low blood glucose?
Name 3 places where glucose sensors are located.
1. Pancreatic islets.
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 hormone from the hypothalamus stimulates the anterior pituitary to release LH and FSH?
What hormone from the hypothalamus stimulates the anterior pituitary to release ACTH?
What hormone from the hypothalamus stimulates the anterior pituitary to release TSH?
What hormone from the hypothalamus stimulates the anterior pituitary to release prolactin?
What can pituitary tumours cause?
1. Pressure on local structures e.g. optic chiasm. Can result in bitemporal hemianopia.
2. Pressure on normal pituitary function; hypopituitary.
3. Functioning tumour can result in Cushing's disease, gigantism and prolactinoma.
How much of the total cardiac output does each kidney receive?
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.
Give an example of the process of autoregulation in regulating GFR.
Pressure in afferent arteriole increases -> stretches the vessel walls -> contraction of smooth muscle -> arteriolar constriction.
Regulating GFR: Why does autoregulation cause arteriolar constriction when the pressure in afferent arterioles increases?
It acts to prevent an increase in systemic pressure reaching the capillaries and so allows GFR to be maintained.
What hormones are involved in pregnancy?
1. Human chorionic gonadotropin.
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 is the function of prolactin?
It stimulates the mammary glands to produce milk (lactation).
What are the functions of prostaglandins?
They have an important role in labor initiation.
What is the function of oxytocin?
Stimulates uterine contraction and milk production stimulated by suckling. It is also thought to help express caring behaviours.
What is the function of relaxin?
It is involved in cervical ripening.
What are the cardiovascular maternal adaptations?
1. Cardiac output increases.
2. Blood pressure decreases.
3. 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.
What are the 3 layers of the uterus?
1. Perimetrium (inner).
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?
1. Latent: little cervical dilation.
2. 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 cortex produce?
What does the adrenal medulla produce?
Adrenaline and noradrenaline (catecholamines).
What are the 3 layers of the adrenal cortex?
1. Zona glomerulosa.
2. Zona fasciculata.
3. Zona reticularis.
What does the zona glomerulosa produce?
Mineralocorticoids e.g. aldosterone.
What does the zona fasciculata produce?
Glucocorticoids e.g. cortisol.
What does the zona reticularis produce?
Androgens e.g. DHEA.
What are steroid hormones synthesised from?
What do steroid hormones bind to so they can be transported through the blood?
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 regulates cortisol synthesis?
What is the function of ACTH?
It acts on adrenal glands to stimulate cortisol synthesis.
What happens to adrenal glands if there isn't enough ACTH?
They will shrink.
What are glucocorticoids released in response to?
What are the physiological functions of cortisol not in response to stress?
1. Permissive action on smooth muscle cells that surround blood vessels; this helps to maintain BP.
2. Maintains concentrations of enzymes involved in metabolic homeostasis.
3. Anti-inflammatory and anti-immune functions: dampens the immune response.
What regulates secretion of adrenaline and noradrenaline?
Autonomic innervation, mainly sympathetic.
Name the 2 hypothalamic nuclei whose axons extend into the posterior pituitary gland via the pituitary stalk.
1. Paraventricular nuclei.
2. Supraoptic nuclei.
Where does the posterior pituitary gland originate from?
Originates from neuronal tissue.
What hormones does the posterior pituitary gland secrete?
What is the function of oxytocin?
It is important in the onset of labour, uterine contraction. It produces milk in response to suckling and is thought to be involved in caring behaviours.
What hypothalamic nucleus contains cells responsible for oxytocin?
What hypothalamic nucleus contains cells responsible for ADH?
What is the affect on ADH secretion if osmolarity increases?
ADH secretion will increase.
What are the physiological functions of cortisol in response to stress?
1. Mobilises energy sources: increases protein catabolism, lipolysis and gluconeogenesis. This help to maintain blood glucose levels.
2. Enhanced vascular reactivity; maintains vasoconstriction with noradrenaline.
3. Suppresses inflammatory and immune responses.
4. 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.
Give 5 actions of angiotensin 2.
2. Increases Na+ reabsorption.
3. Stimulates the adrenal cortex to release aldosterone.
4. Stimulates ADH release.
5. Increase sympathetic activity.
Describe the process of vitamin D activation.
Dietary vit D -> plasma vit D -> 25-OH D (conversion occurs in the liver with the enzyme 25-hydroxylase) -> 1,25-diOH D (conversion occurs in the kidney with the enzyme 1-hydroxylase) -> plasma 1,25-diOH D
What does the mesonephric ridge form?
Mesonephric tubules: these recieve a glomerulus and bowmans capsule forms.
What does the metanephric blastema form?
Excretory units - nephrons.
What causes the kidneys to ascend from the pelvis to the abdomen in the embryo?
1. Reduction in body curvature.
2. Growth of the lumbar and sacral regions.
During embryonic life what structure is responsible for the excretion of waste products?
The placenta - not the kidneys!
Describe the migration of primordial germ cells.
Originate in the epiblast and migrate through the primitive streak. They migrate along the dorsal mesentery of the hind gut to reach and invade the genital ridge by the 6th week.
What ligament attaches the uterus to the pelvic wall?
The broad ligament.
What does the broad ligament divide the pelvic cavity into?
1. The uterorectal pouch.
2. The uterovesical pouch.
What does the vagina develop from?
Upper 1/3 - mullerian duct. Lower 2/3 - urogenital sinus.
What causes the mullerian duct to degenerate in the male?
Sertoli cells release MIF.
What line marks the junction between the upper 2/3 and lower 1/3 of the anal canal?
The pectinate line.
What is the epithelium of the anal canal above the pectinate line?
What is the epithelium of the anal canal below the pectinate line?
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?
Which urethral sphincter is composed of skeletal muscle?
External urethral sphincter.
Describe what happens in micturition.
The bladder fills and stretch receptors are stimulated. Afferent impulses stimulate parasympathetic action of detrusor muscle; it contracts. The urethral sphincters relax, this is mediated by inhibition of the neurones to them. The PAG is stimulated.
What is the periaqueductal grey?
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.
1. Stress incontinence.
2. 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.
The differentiation of spermatids into spermatozoa. The process involves cell remodelling.
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.
Oogonia undergo mitotic divisions in utero. The oogonia develop into primary oocytes and begin a meiotic division by replicating their DNA. They do not complete meiosis 1 in the foetus = meiotic arrest. At puberty there is renewed activity in the ovaries and those oocytes destined for ovulation complete meiosis 1. Meiosis 2 occurs if the secondary oocyte is fertilised; this will produce one ovum.
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.
1. Increased amplitude of GnRH and GHRH.
2. Increased levels of FSH, LH and sex steroids.
3. Increased levels of growth hormone.
What factors can influence puberty?
1. Nutrition (body mass).
2. Leptin, insulin (hormones).
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.
What are the 2 phases of the menstrual cycle?
1. The follicular phase.
2. The luteal phase.
The phases are approximately equal in length and are separated by ovulation.
What happens in the follicular phase?
The mature follicle and secondary oocyte develop.
What is the luteal phase?
It occurs after ovulation until corpus luteum death.
Menstrual cycle: what causes oestrogen levels to rise in the follicular phase?
Oestrogen is released from granulosa cells and also from the developing and dominant follicle.
Menstrual cycle: what is the effect of oestrogen at low levels on the gonadotropins?
At low levels oestrogen inhibits gonadotropin release.
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 effect of the LH surge?
Menstrual cycle: why do progesterone and oestrogen levels increase following ovulation?
The ruptured follicle has transformed into a corpus luteum which releases large amounts of progesterone and oestrogen.
Menstrual cycle: why do LH and FSH levels decrease after ovulation?
They are inhibited by the high progesterone and oestrogen concentrations.
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.
What is the acrosome reaction?
Many sperm move through granulosa cells to bind with the zona pellucida. This binding triggers acrosomal enzymes from the sperm's head to digest through the zona pellucida. The sperm advances through; the first sperm to penetrate the entire zona pellucida and to reach the egg's plasma membrane will fuse.
What is the function of block to polyspermy?
It is a mechanism to prevent the entry of additional sperm fusing with the egg.
Describe the mechanism of block to polyspermy.
1. The egg releases contents of secretory vesicles by exocytosis.
2. Enzymes from the vesicles enter the zona pellucida and inactivate sperm binding sites and harden the zona pellucida.
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.
How does PTH increase serum Ca2+?
1. It increases bone resoprtion meaning more Ca2+ is released into plasma.
2. It acts on the kidneys to increase Ca2+ reabsorption meaning less is excreted in the urine.
3. It stimulates the enzyme 1-hydroxlyase and so increases 1,25-diOH D formation. This compound increases absorption of Ca2+ into the blood from the intestine.
PTH action affects serum calcium and phosphate. What is the mechanism that prevents serum phosphate from increasing too much?
It inhibits the reabsorption of phosphate ions in the kidney leading to increased excretion of phosphate ions in the urine.
What would happen if Nacl levels reaching the macula densa cells were very low?
The macula densa cells release prostaglandins to act on granular cells which then release renin. Renin release activates RAAS leading to increased GFR.
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 is the full name of T4?
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?
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?
What is the diuretic equivalent to Gitelmans syndrome?
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?
What are the features of Liddles syndrome?
Hypertension and Hypokalemia.
What is the full name of T3?
How many iodine molecules does thyroxine contain?
How may iodine molecules does triiodothyronine contain?
What atom is crucial in thyroid hormone formation?
What cells in the thyroid actively take up iodine in the form of iodide?
In the follicles, what cells does iodide bind to?
Tyrosine residues on thyroglobulin molecules.
What happens when TSH acts on the thyroid?
T1 and T2 molecules are cleaved from their thyroglobulin backbone and join to create T3 or T4.
What process needs to occur before T3 and T4 can be released into the blood stream?
Is more T4 or T3 produced in the thyroid?
Which molecule is active T3 or T4?
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.
Briefly describe thyroid hormone synthesis.
Follicular cells take up iodide. Iodide diffuses to colloid which contains thyroglobulin. Iodide is oxidised to iodine. Iodine attaches to tyrosine residues within thyroglobulin. Tyrosine either binds 1 or 2 iodine molecules forming MIT or DIT. Thyroid peroxidase stimulates MIT and DIT binding forming T3 and T4. Proteolysis of thyroglobulin releases T3 and T4 into the ECF and then into the blood.
What enzyme stimulates T3 and T4 formation in the thyroid?
What 2 molecules can combine to form T3?
What 2 molecules can combine to form 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.
1. The low pH switches on protease inhibitors that prevents corneodesmosome breakdown.
2. 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?
Which hormone that affects blood pressure is produced in the lungs?
Angiotensin 2. (ACE in the lungs converts angiotensin 1 to angiotensin 2).
Aldosterone causes the release of which hormone from the pituitary?
Give 2 tests that can be used to screen for disorders in pregnancy.
What is the most abundant glucocorticoid in humans?
Name the effect cortisol has on three other hormones.
1. Adrenaline - up-regulates beta2 receptors therefore potentiates adrenaline.
2. Insulin - inhibits. Cortisol acts to increase blood glucose.
3. Glucagon - activates. Cortisol acts to increase blood glucose.
What hormone causes production of sperm?
In what specific cell in the testes do sperm mature?
Name 2 hormones that regulate melanin secretion.
Give 6 functions of the skin.
1. Barrier to infection.
2. Protection against trauma.
3. Protection against UV.
5. Vitamin D synthesis.
What organelle stores melanin in melanocytes?
Give 3 histological characteristics of the secretory phase.
1. Spiral arteries.
2. Decidualised stroma.
4. Torturous glands.
What cells in the parathyroid detect Ca2+ levels?
What does ANP inhibit the release of?
ANP is a vasodilator and acts to decrease blood pressure.
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?
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?
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 act on granular cells and trigger renin release.
What enzyme is found only in the zone glomerulosa?
What 2 structures make up the metanephros?
1. Metanephric blastema.
2. Ureteric bud.
What is the ureteric bud an outgrowth of?
The mesonephric duct.
What is dihydrotestosterone?
An active metabolite of testosterone. It modulates external genitalia differentiation -> penis, scrotum and prostate.
What are the start and end products of spermiogenesis?
What are the start and end products of spermatogenesis?
Spermatogonia undergo mitosis forming primary spermatocytes. Type B primary spermatocytes undergo meiosis forming secondary spermatocytes and then spermatids.
What are the start and end products of mitosis in oogenesis?
End: primary oocyte.
What are the start and end products of meiosis in oogenesis?
Start: primary oocyte.
Middle: secondary oocyte.
End: 1x ovum.
Which layer of the endometrium is shed in the menstrual cycle?
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?
What is the diuretic equivalent to Bartter's syndrome?
What are the characteristic features of Bartter's syndrome?
Hypokalemia, low BP, alkalosis.
What part of the nephron is affected by Gitelman's syndrome?
What channels are affected by Gitelman's syndrome?
What is the diuretic equivalent to Gitelman's syndrome?
What are the features of Gitelman's syndrome?
Hypokalemia, hypomagnesemia, low BP.
What part of the nephron is affected by Liddle's syndrome?
The collecting duct.
What channels are affected by Liddle's syndrome?
What are the characteristic features of Liddle's syndrome?
Hypokalemia and increased BP (too much Na+ reabsorption).
Name 2 hormones that are produced elsewhere but are activated in the kidney.
2. 25-hydroxyvitamin D.
How does increased serum sodium affect calcium reabsorption in the kidney?
There would be increased calcium reabsorption. Calcium is coupled with sodium reabsorption in the proximal tubules.
What are the 6 stages of implantation?
3. Differentiation of trophoblast.
4. Invasion of endometrium.
5. Decidual reaction.
6. Maternal recognition.
What are C-cells also known as?
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?
2. Thyroxine binding globulin.
Name 2 prostaglandins released in labour.
2. PGF2-alpha (main one).
Give 3 functions of the placenta.
1. Provides nutrition to the foetus.
2. Gas exchange.
3. Waste removal.
4. 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.