Urogenital system physiology

negative feedback system example

thyroid hormone regulation

rise in T3 and T4 inhibits TRH release from hypothalamus and TSH from pituitary

postive feedback system example

Oxytocin release during childbirth stimulates contractions -> contractions stimulate  more oxytocin release

location of hypothalamus (2)

located at base of brain above pituitary gland

Connects pituitary via the infundibulum

function of hypothalamus

Paraventricular and supraoptic nuclei produce oxytocin and vasopressin → inhibits or stimulates pituitary glands

function of posterior pituitary gland

secretes hormones synthesised in the hypothalamus into circulation

steps of posterior pituitary gland hormone release (4)

1. Hypothalamic neurons synthesize oxytocin or anti-diuretic hormone (ADH) -> vasopressin

2. Oxytocin and ADH transported down the axons of the hypothalamic-hypophyseal tract to posterior pituitary gland

3. Oxytocin and ADH stored in axon terminals in posterior pituitary

4. Oxytocin or ADH released into blood when hypothalamic neurons action potential reach axon terminals

function of anterior pituitary gland

production of FSH, LH, ACTH, TSH, GH, and prolactin

regulated by hypothalamic releasing and inhibiting hormones

steps of anterior pituitary gland hormone release (4)

1. Hypothalamic neurons synthesize releasing or inhibiting hormones -> release into primary capillary plexus when stimulated

2. Hypothalamic hormones travel through portal veins to anterior pituitary -> stimulate or inhibit release of hormones made in anterior pituitary

3. Releasing hormones stimulate anterior pituitary to secrete hormones into secondary capillary plexus -> empties into blood circulation

hypophyseal protal system - components (3)

composed of two capillary plexuses connected by veins

Primary capillary plexus

Hypophyseal portal veins

Secondary capillary plexus

tropic/ trophic - def

hormones secreted by anterior pituitary -> stimulate hormone secretion from other glands

Alternative name for stimulating hormones -> SH

_trophs - def

cells that secrete trophic/ trophic hormones

_statins - ef

inhibiting hormone

median eminence - summary

small swelling near hypothalamus that helps release hormones into the body

releasing hormones - function

secreted from median eminence to stimulate hormone production by other glands

controlled by negative feedback

steps of reelase hormone to target organ hormone release (4)

1. Releasing hormone released by hypothalamus

2. Anterior pituitary gland releases hormone 1

3. Hormone 1 acts on endocrine target organ

4. Endocrine target organ releases hormone 2

function of TRH

TRH stimulates TSH and prolactin release from pituitary → acts on thyroid gland to secrete TH

function of CRH

stimulates ACTH release from pituitary -> acts on adrenal gland to produce glucocorticoids

function of GnRH (2)

stimulates FSH and LH release from pituitary -> acts on reproductive endocrine organs - testes and ovaries

FSH: Stimulates follicle development in ovaries, spermatogenesis in testes

LH: Triggers ovulation, stimulates testosterone production in Leydig cells

cell that releases gonadotropin-releasing hormone (GnRH{)

gonadotrophs

derivation of hormones (3)

Amino acids -> hydrophilic or hydrophobic

Protein hormones -> hydrophilic

Lipid derived -> hydrophobic

• Cholesterol/ phospholipids

consequence of lipid soluble hormones

Lipid soluble molecules cannot dissolve in water -> need to be bound to hydrophilic binding protein in circulation and then offloaded to diffuse into target cell

Lipid soluble steroid hormones bind to hydrophilic carrier proteins inside cells to be transported into nucleus

benefit of binding proteins

Binding proteins can compartmentalize steroid hormones

Testosterone can diffuse locally into seminiferous tubules and into the systemic circulation -> negative feedback results in increased circulating testosterone inhibiting LH production by Leydig cells

FSH stimulates Sertoli cells to produce androgen binding protein -> concentrates testosterone at site of spermatogenesis

feature of binding proteins

Different proteins have different affinities for various hormones -> precise regulation of hormone availability in bloodstream

examples of binding proteins (3)

Albumin = buffers steroid concentration in blood

• Abundant, low specificity and low affinity

Corticosteroid-binding globulin = high specific and affinity for glucocorticoids and progesterone

• Low concentration in blood

Sex hormone binding globulin = binds to androgens and oestrogen

mitosis - summary

diploid somatic cell with 2n chromosomes

meiosis - summary

haploid gamete cell with n chromosomes

Spermatogenesis = four daughter sperm cells

Oogenesis = single ovum and three functionally redundant bodies

meiosis - summary steps

1. Prophase I: Homologous chromosomes pair and crossing over occur

2. Metaphase I: Tetrads align along the metaphase plate

3. Anaphase I: Homologous chromosomes separate

4. Telophase I: Two haploid cells formed, each with duplicated chromosomes

Meiosis II = similar to mitosis but sister chromatids separate and results in four haploid gametes

spermatogenesis - process

diploid germ cell -> undergoes mitosis to produce two diploid daughter cells

Cell 1 (type a) remains germ cell

Cell 2 (type b) undergoes spermatogenesis

ooogenesis - process (4)

Oogonium = diploid germ cell -> undergoes mitosis during foetal period to produce 7 million daughter cells

• Atresia decreases germ cell numbers to 2 million

Meiosis begins around 12-25 week development to produce primary oocyte

Primary follicle forms during 14-36 week development and then meiosis undergoes arrest in prophase 1 -> sister chromatids

sperm vs oocyte production timeline

spermatogenesis = puberty → 80+

oogenesis = foetal development → before birth

hormonal regulation of spermatogenesis - steps (6)

1. Kisspeptin hypothalamic neurons stimulate GnRH hypothalamic neurons to produce GnRH

2. GnRH secreted into hypophyseal portal system -> drains into anterior pituitary gland

3. Gonadotrophs in anterior pituitary gland stimulated to secrete LH and FSH

4. LH stimulates Leydig cells to produce testosterone -> stimulates Sertoli cell

5. FSH stimulates Sertoli cells to produce androgen binding proteins, promote spermatogenesis and produce inhibin B -> inhibin B inhibits pituitary gonadotrophs to reduce LH and FSH production

6. Increase of testosterone in the blood inhibits kisspeptin hypothalamic neurons -> negative feedback system to reduce further testosterone production

Testosterone breaks down into E2 and DHT

how does anabolic steroir use iunduce infertility - normally without use

set point of testosterone = determined by relatively low levels of circulating T

how does aabolic steroid use induce infertility

1. exogenous androgen enters circulation and exerts excessive negative feedback on hypothalamus and pituitary

2. decrease LH levels and thus less testosterone production and intratesticular levels of testosterone => insufficient spermatogenesis

Also lowers androgen binding protein production -> lower intratesticular levels of T

cells of the follicle (3)

Granulosa cells = FSH sensitive and secrete oestrogen -> analogous to Sertoli cells in testes

• Proliferation of granulosa cells increases concentration of oestrogen in blood

Basement membrane separates oocyte/ granulosa cells from immune system

Thecal cells = LH hormone sensitive and produce androgen precursor to oestrogen production

thecal and granulsa cells - oestrogen production steps (6)

1. LH hormone binds to thecal cell via cell surface LH receptor

2. LH receptor activation stimulates series of events resulting in use of cholesterol for androstenedione production

3. Androstenedione leaves thecal cell and enters circulation or enters granulosa cell

4. FSH binds to granolas cell via cell surface FSH receptor

5. FSH receptor activation stimulates a series of events that promotes conversion of androstenedione to oestradiol via aromatase enzyme

6. Oestradiol exits granolosa cell and enters either circulation or the follicle → oestradiol is the precursor for oestrogen

stages of oogenesis

gonadotropin independent:

1. primary oocytes

2. primordial follicles = primary oocytes + granulsa cells

3. secondary follicles = primordial follicle + thecal cells

gonadotropin dependent:

4. antral follicles → follicle growth due to FSH production

5. preovulatroy follicles → LH and FSH production for further growth

6. mature oocyte → resumption of meiosis then ovulation

• LH stimulates formation of corpus luteum

gonadotropin-dependent stimualtion of oogenesis restart

FSH production during puberty stimulates primary oocyte to develop into secondary oocyte → meiosis I to produce haploid cell

stimulation of meiosis II to be completed

fertilization

impact of rise in FSH levels

stimulates follicle growth → multiple follicles begin to mature each cycle

follicular dominance - def

single follicle matures for ovulation -> can take several months for a single follicle to mature to ovulation

Dominant follicle continues to grow and produce oestrogen -> other follicles undergo atresia (programmed cell death)

selection of dominant follicle - steps from follicle growth to selection (7)

1. Anterior pituitary gland secretes FSH and LH

2. FSH stimulates follicles to grow and LH stimulates thecal cells to form corpus luteum

3. Growth of follicles secretes oestrogen -> increased circulating oestrogen levels

4. Corpus luteum secretes progesterone, oestrogen, relaxin and inhibin

5. Increase in oestrogen levels suppresses FSH and LH secretion

6. Inhibit inhibits release of FSH and LH

7. Decrease in FSH triggers atresia of less matured follicles -> follicular dominance

gonadotropin-dependent stimulation of ovulation - hormone

surge in LH

gonadotropin-dependent stimulation of ovulation - steps (5)

1. High levels of oestrogen from almost mature follicle stimulates release of more GnRH and LH

2. GnRH promotes release of FSH and more LH from anterior pituitary gland

3. LH surge stimulates ovulation -> dominant follicle forms blister like protrusion on ovary surface and then ruptures and contents released into peritoneal space

4. Remaining granulosa and thecal cells left over in ovary will form corpus luteum

5. Corpus luteum secretes progesterone and some oestrogen

hormonal changes throughout menstrual cycle - follicular, pre-ovulatory ovulation and luteal phase

Follicular phase: oestrogen levels rise as follicles mature -> oestrogen suppresses FSH secretion so FSH levels drop

Pre-ovulatory: oestrogen peaks -> triggers LH surge

Ovulation: 24-36 hours after LH surge begins

Luteal phase: oestrogen, LH and FSH levels fall and progesterone rises

type of rhythm LH levels follow throughout the day

ultradian → due to pulsatile release of GnRH

LH and FSH levels throughout the day

LH levels in blood over 24 hours is relatively constant despite pulsatile release

FSH levels relatively constant throughout day

relation between oestrogen and LH just prior to ovulation

Increase in oestrogen concentrations in the blood increases amount of LH released per burst

oestrogen surges just prior to LH surge during menstrual cycle → indicates LH surge is a function of blood oestrogen concentration

hormonal interactions in ovarian and uterine cycles - summary (6)

1. Anterior pituitary gland secretes FSH and LH

2. FSH stimulates follicles to grow and LH stimulates thecal cells to form corpus luteum

3. Follicular growth and formation of corpus luteum increases secretion of oestrogens and progesterone

4. High levels of oestrogens without progesterone or low levels of both stimulates release of GnRH, LH and FSH -> surge in LH and stimulation of ovulation

5. Moderate levels of oestrogens inhibit secretion of GnRH, FSH and LH

6. Inhibin inhibits secretion of FSH and LH

early follicular phase - hormone interactions

1. growing antral follicles recruited by FSH

2. moderate E2 and inhibin but no progesterone inhibits i. kisspeptin neurons to decrease stimualtion of GnRH neurons for decreased GnRH release and ii. gonadotropes to decrease FSH and basal LH

3. low FSH stimulates follicular atresia and selection of dominant follicle

late follicular phase - hormone interactions (4)

1. dominant follicle and high E2 but no progesterone switches to positive feedback stimulation of kisspeptin neurons and gonadotropes

2. kisspeptin neurons stimulate GnRH neurons for rapid GnRH pulses → stimualtes gonadotropes

3. increased stimulationg of gonadotropes = LH surge

4. LH surge stimulates follicle rupture and ovulation + formation of corpus luteum

mid luteal phase - hormone interactions

1. high progesterone and inhibin iinhibits kisspeptin neurons and gonadotropes

2. decreased kisspeptin stimualtion of GnRH neurons → slow GnRH pulses

3. decreased gonadotrope stimualteion → low basal LH and FSH

4. actie coprus luteum maintained

coprus luteum without no implanttion - hormone interactions (5)

1. no implantation = no hCG

2. corpus luteum will produce progesterone and oestrogen

3. progesterone suppresses LH secretion → corpus luteum becomes necrotic and forms corpus albicans

4. corpus albicans does not produce hormones → androgen levels will fall and spiral arteries no longer viable

5. endometrial tissue becomes nectoric → shed in form of menstruation

late luteal phase without implantation - hormone interactions

1. corpus albicans produces no hormones → loss of negative feedback from ovary

2. kisspeptin neurons stimualtes GnRH neurons for rapid GnRH pulses

3. GnRH stimulates gonadotropes → FSH peak

4. FSH recruits large antral follciles for new cycle to begin

layers of uterus (2)

stratum basalis and stratum functionalis

uterine cycle - steps (6)

1. Striatum functionalis = very small after menstruation

2. Stratum functionalis grows in response to oestrogen -> thickening of endometrium in preparation for fertilization and implantation

   • Spiral arteries grow as thickness of striatum functionalis (endometrium) expands -> blood supply to proliferating cells

3. Post ovulation = formation of corpus luteum -> secretes progesterone and oestrogen

   • Progesterone keeps spiral arteries viable

4. Progesterone will suppress LH secretion by pituitary gland via negative feedback loop -> corpus luteum will become necrotic and form corpus albican

5. Corpus albican does not produce hormones -> androgen levels will fall and spiral arteries no longer viable

6. Endometrial tissue becomes necrotic -> shed in the form of menstruation

hormone interactions - post-implantation of fertilzed oocyte into endometrium (4)

1. oocyte forms chorion

2. chorion secretes human chorionic gonadotropin (hCG)

3. hCG stimulates ovary to continue progesterone and oestrogen production to sustain corpus luteum

4. continued production of progesterone to maintain uterine lining → inhibits LH and FSH production -

features of menopause (5)

• Fewer ovarian follicles

• Decreased oestrogen secretion

• Impaired proliferation phase

• No uterine cycle

• No FSH/ LH inhibition

cause of decreased oestrogen and progesterone release during menopause

oocyte depletion and oocyte insensitivity to gonadotropins LH and FSH

loss of negative feedback inhibition of GnRH, LH and FSH -> dysregulation of gonadotrophs

hormone release - pre-puberty and during puberty

Pre puberty: no surges in gonadotrophs

During puberty: some surges in gonadotrophs during night cycles -> stimulate follicles to begin maturing

hormone release - reproductive years and menopause

Reproductive years: pulses of gonadotroph secretion -> correlate with ovarian cyclw

Menopause: pulses of LH and gonadotroph release but no oestrogen release

main functions of kidneys (2)

1. Excretion of waste

2. Maintenance of ECF composition and volume

main composition of urine

mostly composed of plasma → filtered out of blood

2L urine requires 200L of plasma → most reabsorbed

process of urine production int he kidneys (3)

1. Filtration of plasma

   • Molecules that can cross filtration barrier = carried into filtrate in same concentrations as found in plasma

   • Molecules too big too fit through filtration slits = withheld in plasma -> do not enter filtrate

1. Secretion -> molecules found in higher concentrations in urine than plasma

   • Secretion -> molecules actively moved into filtrate during urine formation

   • Reabsoption -> concentrated in urine as reabsorption along with water is prevented

2. Reabsorption of substances into the filtrate

   • Molecules actively removed from filtrate -> lower concentration in urine than plasma

components of nephron - arteries (3)

afferent arteriolr leads blood into bowman’s capsule

efferent arteriolr leads blood out of nephron

bowman’s capsuel has web of capillaries (glomerulus) for blood filtration → leads to tubules

components of nephron - tubules (7)

1. bowman’s capsule

1. prximal tubule

2. descending limb of loop of henle

3. ascending limb of loop of henle

4. distal tubule

5. connecting tubule

6. collecting duct → goes to bladder

secretion - def

movement of molecules from peritubular capillaries into renal tubular lumen

Substance must pass the epithelial cells lining the tubule

reabsorption - def

substance passes form tubular lumen and into interstitial fluid via epithelial cells

Substance must pass the epithelial cells lining the tubule

excretion - def

substance removed from body and cannot be recovered

how do glomerular capilalries allow for efficient exchange

apical surface of tubular epithelial cells have microvilli to increase SA

composition of filtration barrier in nephrons (3)

1. fenestrated endothelium (most deep) → large holes for water and small solutes to pass but block RBC

2. basal lamina → physical size and chemical charge barrier to repel negatively charged palsma proteins inc albumin

3. podocyte (most superficial) → epithelial cells with foot processes that extend form cell body to form narrow filtration silts (final molecular seive)

glomerulus - concetration of filtrate vs plasma

equal concentration → filtration is passive

function of mesengial cells in bowman’s capsule

provide scaffold which supports the glomerular capillaries suspended in bowman's capsule

Can also contract to alter surface area for filtration

glomerular filtration rate - unit

volume of plasma filteres by glomerulus per unit time

filtration fraction - def

portion of plasma that is filtered per pass

renal clearance - def

rate of urinary excretion of a substance relative to its plasma concentration

renal clearance equation

(U x V) / P, mL/min

U = urine concentration of solute

V = urine volume per unit time

P = plasma concentration of solute

clinical measurement of renal clearance procedure (3)

1. 24-hour urine collection: a) Patient collects ALL urine over 24 hours b) Total volume measured (typically 1-2 L/day)

2. Blood sample: Taken during or immediately after collection period

3. Calculation considerations: a) Ensure complete collection b) Account for any spillage or missed voids

factors affecting renal clearance (4)

• Filtration -> affected by GFR and plasma concentration

• Reabsorption

• Secretion

• Metabolism

inulin - role in renal filtration rate

ideal susbtance for measureing GFR → 100% clearance rate as it is filtered and exogenous but not reabsorpoted, secreted or metabolised

most important force affecting GFR

hydrostatic pressure in glomerular capillary

high hydrostatic pressure allows for filtration along length of capillary

no oncotic pressure in bowman’s space → no albumin in lumen

relation between plasma oncotic pressure along glomerular capillary and albumin concentration in plasma

increase = increase

impact of dilating afferent arteriolr on rate of filtration

GFR increases as dilation increases → efferent arteriol is unchanged

rate of filtration = determined principally by hydrostatic pressure in glomerular capillary -> dilating arteriole will allow more blood in -> increase in pressure and increase in GFR

how is GFR stabilised

by autoregulation → if MAP increases from 90 to 110mmHg, GFR remains near constant

composution of autoregualtion (2)

myogenic response = local arteriole response → independent of endothelium or any nervous input

tubuloglomerular feedback = regulation of blood flow to glomerulus based on NaCl content in filtrate of ascending limb of the loop of Henle

impact of myogenic response on autoregualtion in GFR

Stretch in smooth muscles of artery walls due to increased pressure = contraction -> reduced diameter of artery to increase resistance

impact of tubuloglomerular feedback on autoregulation in GFR

NaCl = sensed by macula densa cells in thick ascending limb (Tal) -> loops begin its own glomerulus to allow for communication with afferent arteriole

High NaCl in filtrate stimulates macula densa to release paracrine signal -> causes afferent arteriole constriction  -> decreased blood flow through glomerular capillaries -> decreased filtration -> decreased GFR

juxtaglomerular apparatus - composition and implication

collection of structures that form due to ascending limb of loop of Henle looping behind its own glomerulus such that the afferent and efferent arterioles are at posterior margin of Bowman's capsule

Filtrate flows from TAL into distal convoluted tubule -> passes close to glomerulus