S2 Development of the urinary system and Measurement of Kidney function

Question 1

how does the urinary system develop in summary

Answer 1

embryonic kidney and gonad both originate from the urogenital ridge, a region of intermediate mesoderm
the organisation of intermediate mesoderm leads to 3 system developing sequentially , the disappearance of one system marks the start of the next

Question 2

where does the kidney system first appear

Answer 2

cervical region- the pronephros

Question 3

describe the pronephros

Answer 3

the first kidney system - never functions in humans
produces the pronephric duct which extends to the cloaca and drives the development of the next stage (becoming the mesonephric duct)
appears - start of week 4
regresses- end of week 4
functional - no

Question 4

describe the mesonephros

Answer 4

the mesonephros sprouts tubules
uses duct by pronephros to connect to the cloaca
these tubules plus the mesonephric duct make up the embyronic kidney
the mesonephric duct sprouts the ureteric bud, which induces development of the definitive kidney
the mesonephric duct also has role in the development of the male reproductive tract

Question 5

describe the metanephros

Answer 5

induces the development of the definitive kidney within the intermediate of the caudal region of the embryo
it expands and branches into the metanephric blastema forming the definitive kidneys structure - minor calyx and major calyx
the collective system is derived from the ureteric bud itself
the excretory component is derived from the intermediate mesoderm under the influence of the ureteric bud

Question 6

describe the ascent of the kidney

Answer 6

the metanephric kidney first appears in the pelvic region
undergoes apparent caudal to cranial shift crossing the arterial fork formed by vessels returning blood from the foetus to the placenta. gonad in turn descends

Question 7

do the kidneys move during development

Answer 7

no, development is cranial to caudal and the trunk just extends downwards making it appear as though the kidneys move

Question 8

does the blood supply change as the kidneys ascend

Answer 8

as the kidneys ascend, they receive their blood supply from new branches and the original disappear.
H/e if the original remain they form accessory renal arteries which are end arteries so have no collateral blood supply

Question 9

what is renal agenesis

Answer 9

ureteric bud fails to interact with the intermediate mesoderm so cant form kidney. can affect one (unilateral) or both (bilateral, can’t survive ) kidneys

Question 10

describe migration defects of the kidney

Answer 10

if a kidney fails to cross the arterial fork, it ends up much lower than it should be
during ascent of the kidneys, the kidneys lie extremely close to one another, their inferior poles can fuse and can form a horseshoe kidney (B)

Question 11

describe duplication defects of the kidney

Answer 11

splitting of the ureteric bud, results in an ectopic ureteral opening, for e.g. into the vagina or urethra, bypassing the bladder and causing incontinence

Question 12

what is cystic kidney disease

Answer 12

multicystic kidney disease - atresia of ureter

polycystic kidney disease - recessive, presents early and poor prognosis

Question 13

what is the urogenital sinus

Answer 13

the bladder is a hindgut derivative, it is derived from the caudal portion of the primitive gut tube formed during embryonic folding in the fourth week of development
the cloaca is divided by the urorectal septum into the urogenital sinus( future bladder and urethra) and anorectal canal ( future rectum and anal canal)
the lumen on the allantois becomes obliterated to become the urachus - the median umbilical ligament in adults

Question 14

what is the structure to the urogenital sinus

Answer 14

superior part connects to umbilicus
majority differentiates to form the urinary bladder
inferior part develops into the urethra

Question 15

how does the male bladder form

Answer 15

mesonephric duct reaches urogenital sinus
ureteric bud sprouts from MD - ureteric bud will become ureter opening into the bladder
smooth musculature appears
UBs and MDs make independent openings in UGS
prostate and prostatic urethra formed. MD is maintained in males forming the prostate and ducts of the male reproductive system

Question 16

how does the female bladder form

Answer 16

develops in the same way as men but without male hormones, the mesonephric duct regresses, therefore females do not form the prostates or the tubes of the male reproductive system

Question 17

how is the urethra formed

Answer 17

the female urethra is formed by the pelvic part of the urogenital sinus
the male urethra is divided into four parts
1. pre - prostatic
2. prostatic
3. membranous
4.spongy

Question 18

what is hypospadias ?

Answer 18

a defect in fusion of urethral folds. the urethra opens onto the ventral surface, rather than at the end of the glans

Question 19

how is kidney function measured

Answer 19

measured in terms of GFR ; the amount of filtrate produced from blood flow per unit time
normal GFR is 90-120 ml/min/1.73m2
the normal total glomerular filtrate per day is 140-180 L/day
depends on factors such as gender size age pregnancy

Question 20

when does nephron development finish

Answer 20

by 35-36th week of foetal development
premature and LBW infants have lower nephron numbers
foetal excretion predominantly via placenta

Question 21

why does GFR decline after ~ 30 yrs

Answer 21

loss of functioning nephrons

kidney volume reduces with age

Question 22

describe compensatory hypertrophy of the kidneys

Answer 22

reduced nephron number so exisiting nephrons get bigger
healthy kidney also gets bigger
nephrons end up working harder so can wear out
occurs mainly in childhood

Question 23

what happens to GFR in pregnancy ?

Answer 23

in pregnancy, GFR increases by 50% kidney size also increases but nephron number remains constant

Question 24

what happens to GFR in disease

Answer 24

GFR varies between people but in one person it remains constant. if it declines this may be due to decline in nephron number or decline in GFR within the individual nephrons

Question 25

what does a fall in GFR indicate

Answer 25

a fall in GFR means that kidney function has worsened a rise means that kidney function has recovered. when kidney function declines slowly , individual nephrons may hypertrophy so actual GFR may not fall until significant damage has occured

Question 26

how do we measure kidney function

Answer 26

cannot measure GFR so we measure clearance - the volume of a substance of plasma cleared of a substance per unit of time
renal clearance = excretion rate / plasma concentration
excretion rate = U * V u = amount in urine v= urine flow rate

Question 27

what criteria should a substance meet to measure kidney clearance

Answer 27

be produced at a constant rate
be freely filtered across glomerulus
not be reabsorbed or secreted into the nephron
if all these are true then excretion rate = GFR

Question 28

describe inulin clearance

Answer 28

inulin used to measure renal clearance - therefore a surrogate for GFR
most accurate
h/e measurement is impractical due to continuous IV or a catheter

Question 29

what is 51 Cr-EDTA ?

Answer 29

radio-active labelled marker. Approx 10% lower clearance than inulin. used clinically in children or where indication of renal function required e.g kidney transplant

Question 30

what is creatinine and can it be used a measure of kidney function

Answer 30

end product of muscle metabolism
measured by collecting urine over 24 hours and measurement of serum creatinine(via blood sample)
gives an estimate of GFR (10-15%) as creatinine is secreted into the tubule. used in pregnancy

Question 31

how are creatinine levels affected

Answer 31

intake
metabolism
renal excretion
furthermore, muscular black men who eat meat shall have higher serum creatinine than old vegetarian asian females (wth?!)
Serum creatinine remains stable in individuals so most common way to measure but can reflect different GFRS in different individuals
SC levels are inversely proportional to GFR but the relationship is non-linear - downwards curve

Question 32

what is estimated GFR

Answer 32

SC varies between individuals and does not accurately predict GFR. MDRD eGFR is used in some hospitals but it is inaccurate in those without kidney disease, kids, elderly and pregnancies
less accurate with mild kidney disease due to reduction in GFR, reduced nephrons leading to nephron hypertrophy, reduced filtration of creatinine
eGFR taken from serum creatinine and not all changes in serum creatinine are due to change in GFR