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.
- 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.
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.
- Freely filtered.
- Not metabolised.
- 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?
- 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?
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.
- Osmoreceptors in the hypothalamus detect an increase in plasma osmolality.
- The posterior pituitary is signalled to release ADH.
- 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.
- 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.
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.
- ACE inhibitors.
Name 3 urinary buffers.
- 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?
- Anorectal canal.
2. Urogenital sinus.
What are the 3 parts of the urogenital sinus?
- Upper part.
- Pelvic part.
- 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.
- 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.
2. Somatic stem cells - multi-potent.
Name 3 diseases that stem cells could help to cure.
- Parkinsons disease.
- Type 1 diabetes.
What are the 3 main characteristics of stem cells?
- Self renew over long periods.
- 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.
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?
- 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.