Introduction to the Renal System Flashcards
six main functions of the kidney
filtration of blood
detoxification
regulation of blood pressure
regulation of blood pH
regulation of haematopoiesis
making vitamin D
what percentage of cardiac output is used by the kidneys?
20%
which kidney sits more superiorly
left
what size of molecules can pass through the glomerular filter
4nm is cut off
free flow below 1.8nm
how many layers make up the glomerular filter?
three
what is the coarsest layer of the glomerular filter
fenestrae in enthothelial cells
can blood cells pass through the the fenestrae in endothelial cells
no
how is the fenestrae in endothelial cells cleaned
mainly by bulk fluid flow
what is the second layer of the glomerular filter
glomerular basement membrane
what is the glomerular basement membrane made of
mesangial cells
how is the glomerular basement membrane cleaned?
by continuous replacement
what is the finest layer of the glomerular filter?
the slit diaphragm between podocyte processes (e.g. proteins like nephrin)
how is the finest layer of the glomerular filter cleaned
endocytosis of trapped proteins
what is the role of pressure in glomerular filtration
pressure is required to drive filtration against the colloid osmotic gradient back to the filtered plasma
pressure is also required to drive flow
how is pressure controlled through the glomerular filter
by how easily the blood is able to flow in and out which is controlled by afferent and efferent arteriole contraction
does higher pressure lead to more or less flow across the filter
more
what percentage of plasma is removed in the filtrate typically
20%
what type of substance is creatinine
nitrogenous waste
why is creatinine a good substance to use to estimate GFR
it is filtered from the plasma and is not subject to any transport mechanism thereafter/there is not recovery mechanism so everything filtered from plasma is excreted
why can urea not be used to estimate GFR
some can be reuptaken into the blood stream after initial filtration from the plasma
what is GFR
glomerular filtration rate
what is the equation for GFR
GFR = (urine flow rate x concentration of solute in urine)/concentration of solute in plasma
when can the concentration of creatinine rise in the plasma
with muscle use or muscle damage
what would you expect to happen to the plasma creatinine in someone who has just ran a marathon compared to before
it will rise a lot
give examples of types of reasons for the failure of the glomerular filter
congenital
damage by toxins
damage by immune attack
what happens in congenital Finnish nephrotic syndrome
protein leaks into the urine
glomerulosclerosis results
give example of congenital reasons for failure of glomerular filter
nephrin mutants
what is Goodpasture’s syndrome
autoimmune disease which attacks the collagen in the glomerular basement membrane leading to nephritic syndrome resulting in proteins and blood ending up in the urine
can glomeruli be replaced once it is lost
no
what is the cause of many glomerular pathologies
inappropriate behaviour of stem cells ‘trying’ to repair
what 10 molecules of the filtrate need to be recovered
water
sodium
potassium
calcium
chloride
bicarbonate
phosphate
glucose
amino acids
urea
why is some urea recovered from the filtrate
it is used to boost the hypertonicity of the medulla
how are molecules recovered from the filtrate
- cells use a primary active transporter (a basally located Na/K ATPase) to create a strong Na gradient across the apical membrane
- this gradient is used to power cotransport of other substances across the apical membrane
to be continued…
what is the plasma creatinine level in healthy individuals
should be nearly 0 as cleared very quickly
however be aware of muscle damage or overuse causing a large rise
how does dialysis work
dialysate is full of the ‘wanted’ molecules so that there is no net movement of these molecules out of the blood into the dialysate
and the dialysate has not of the waste products so that these move out of the blood into the dialysate
which type of tubules have microvili - distal or proximal
proximal
what type of junctions are between epithelial cells of the glomerulus and what is special about these in the PCT
tight and adhaerens junctions
leaky in PCT
what is the function of tight junctions
stops fluid moving freely
what is the function of adhaerens junctions
sticks cells together
what type of cells make up the PCT and DCT
simple (single layer) epithelial
what cell organelle is very abundant in kidney cells and why
mitochondria
lots of energy is required for active transport
what is the role of ROMK channels
regulated leakage of potassium
what is controls transport of sodium and phosphate by SLC34A1 transporters
parathyroid hormones
what is a characteristic of the filtrate leaving the PCT
it is iso-osmotic with tissue
how is water drawn out of the descending limb of LoH
the membrane is permeable to water but not to salt
the membrane of the ascending limb is almost impermeable to water but is permeable to salt so salt is dumped into interstitial space
this makes the medulla very salty so water is drawn out of the descending limb
how does the concentration of urine change from the end of the PCT to the start of the DCT
water drawn out in descending limb - more concentrated
salt drawn out in ascending limb - less concentrated than when it started
less concentrated at start of DCT than PCT
where is the collecting duct found and what sort of environment is this
medulla
very salty
what three things happen in the collecting duct and how is this controlled
- urine is concentrated because water leaves by aquaporin channels into the very salty medulla
this is controlled by vasopressin - the urine receives K+ and H+ to control acid-base balance
- urine loses some urea which contributes to the hypertonic zone in the medulla
what is the vasa recta
capillary networks which supply the medulla/LoH
what are vasa recta permeable to
very permeable to salt and water
how does blood flow compare to urine flow in the LoH
they move in opposite directions
efferent arteriole moves down the ascending limb of LoH and returns towards the renal vein up the descending limb of LoH
what structures are found within the renal cortex
renal corpuscles
PCT
DCT
what structures are found within the renal medulla
LoH
collecting duct
is GFR independent or dependent of systemic blood pressure
relatively independent
where is the juxtaglomerular apparatus found
the afferent and efferent arteriole cells which are in contact with the macula densa cells of the DCT
where is the macula densa
on the DCT where it in contact with the afferent and efferent arterioles
how does feedback and regulation work between the macula densa and juxtaglomerular apparatus
- macula densa cells pump NaCl from the filtrate at a rate limited by its concentration in the filtrate
- the JG cells respond to high NaCl by making adenosine (NaCl will be high when the filtrate is flowing too fast for proper recovery)
- adenosine constricts the afferent arteriole
- this reduces glomerular blood pressure which therefore reduces GFR
what would be a problem that would arise from relying only on the local feedback mechanisms of the macula densa and JG apparatus
if DCT NaCl was high because someone had eaten a lot of salt, reducing GFR would be bad as the excess salt needs to be cleared
what three systems control GFR
macula densa and JG apparatus
renin-angiotensin system
atrial natruietic peptide (ANP)
what is the role of ANP
blocks the Na+ re-uptake channel collecting ducts and causes more sodium loss
where in the renal tubule is K+ regualted
the collecting duct
elsewhere its movement is just driven by the Na+ gradients
what two processes control K+ regulation in collecting duct
- potassium reabsorbed in exchange for hydrogen excretion
- collecting duct principle cells secrete potassium in proportion to K+ in tissue
what happens to K+/H+ exchangers in collecting duct when body is in acute acidosis
more H+ is excreted so more K+ is reabsorbed
what happens to K+/H+ exchangers in collecting duct when body is in acute alkalosis
less H+ is excreted so less K+ is reabsorbed
what happens to collecting duct principle cells in response to chronic hypokalaemia
tyrosine phosphorylation of channels occurs
the channels are then withdrawn from the membrane
so phosphorylation excretion decreases
the opposite happens in chronic hyperkalaemia
what problems can arise due to loop diuretic use
K+ reabsorption in the TAL of LoH gets messed up
high calcium in urine can cause stones
why are diuretics useful in hypertension treatment
the dilute urine in the macula densa fools the tubuloglomerular feedback system into thinking blood pressure is too high
so renin release is stopped
this helps reduce BP
why does fluid loss caused by diuretics not lower high blood pressure
because the fluid loss will be replaced by drinking
MoA of carbonic anhydrase inhibitors
inhibit bicarbonate uptake in PCT so keep the lumen contents more osmotic
this inhibits water uptake later in the tubule (e.g. in the collecting duct)
why do diabetics pee more
glucose can only be reabsorbed in the PCT
if there is too much glucose for it all the be reabsorbed it will remain in the filtrate
therefore the filtrate will be more concentrated and less water will be able to be reabsorbed into the body
so more will be peed out
what is bilateral agenesis
how common is it
prognosis
no kidneys forming
rare
fatal after birth
what is unilateral agenesis
how common is it
prognosis
only one kidney forms
1 in 500
fine as long as kidney stays healthy
what are congenital cystic diseases
how common is it
overgrowth of the collecting ducts and/or fluid pumps are orientated the wrong way round
common
what is Wilms’ tumour
‘islands’ of kidney remain in the primitive state and make a tumour very similar to normal developing kidney
what are supernumerary ureters
many ureters
one enters trigone normally but other often ends up elsewhere on the uregenital sinus and therefore empties somewhere else (e.g. vagina or gut)
how does a pelvic kidney form
kidney gets caught in aortic bifurcation and fails to ascend
what is a horseshoe kidney and how is it formed
2 kidneys fuse
often occurs when two pelvic kidneys are forced together
what is a urachial fistula
the passage to allantois should have closed but does not
what is a urachial cyst
the passage to allantois closes at the body wall end, parts remain between there and the bladder
what is a urethral valve
the ureter opens too low so that the prostate balloons under pressure and traps urine, causing more pressure
how do rectovaginal, rectoprostatic and rectocloacal canals occur
as a result of failure of the folds to separate the cloaca
what is hypospadias
the urethral orifice fails to migrate to the end of the penis
what drug type does Bartter’s syndrome mimic
loop diuretics
clinical effect of Bartter’s syndrome
loss of Na+
loss of K+
loss of Ca+
loss of lots of water
what drug type does Gitelman’s syndrome mimic
thiazide diuretic
clinincal effect of Giltelan’s syndrome
loss of Na+
loss of K+
loss of some water
what is the clinical effect of Liddle’s syndrome
body volume expansion and hypertension
treatment of Liddle’s syndrome
amiloride - potassium sparing diuretic
cliniclal effects of pseudohypoaldosteronism
Na+ loss and K+ retention
symptoms mimic low aldosterone
but actually have high aldosterone as trying to correct the problem but can’t because of inactive ASC channels
where is the molecular defect in nephrogenic diabetes insipidus
aquaporins
symptoms of nephrogenic diabetes insipidus
polyuria
polydispia
what is addisions disease
destruction of the adrenal glands
what is the clinical effect of addisons disease
loss of Na+
retention of K+
loss of water - hypovolaemia
all due to the effects of low aldosterone
clinical effects of psychogenic polydipsia
whole body hypo-osmolarity
where do kidneys first develop in humans and what is the earliest form of kidney called
in thoracic region
mesonephros
cloaca meaning
a common cavity at the end of the digestive tract for the release of both excretory and genital products in vertebrates (except most mammals) and certain invertebrates
where does the mesonephros drain
via its mesonephric draining duct to the cloaca
what happens to the mesonephros in females
it regresses
what develops next to the mesonephros in males
testes
where are the rete testis and epididymis formed
in ‘hijacked’ mesonephric tubules
what three structures arise from the mesonephric duct
vas deferens and ejaculatory duct and seminal vesicles
what pulls the testis into the scrotum
gubernaculum
what type of kidney is used by adults mammals
metanephric
how is the collecting duct system of the metanephric kidneys and ureters formed from the nephric duct
a side branch forms from the nephric duct close to where is empties into the cloaca
this is the ureteric bud which gives rise to the ureters
the end of the ureteric bud/ureters undergoes repeated branching
this forms the collecting duct system of the metanephric kidneys
how are nephrons formed
cells surrounding the branching ureteric bud multiply and groups of cell condense in response to signals from the ureteric bud
what impact does a low protein maternal diet have on kidney formation in a rodent fetus
less nephrons are formed
how do the DCT and JG apparatus of the same nephron stay in contact with each other
the nephron begins as a curved tube and middle extends down into the medulla so the ends stay together
at what stage of development do kidney ascend
week 10
don’t really ascend but rest of body elongates past them
what three folds subdivide the cloaca into the anorectal canal and urogenital sinus
Tourneaux fold
r and l Rathke folds
what structure does the bladder form from
the upper part of the urogenital sinus
what structure runs roughly next to the nephric ducts
mullerian ducts
what happens to mullerian ducts in males
regress because of secretion of anti mullerian hormone
how is the fallopian tubes and uterus and vagina formed
the ends of the mullerian ducts fuse and contact the urogenital sinus
the unfused parts are fallopian tubes
the fused parts are the uterus and top of the vagina
the lower vagina is formed from the urogenital sinus itself
where does the prostate form from
urethra in early foetal life
where does the urogenital sinus open to the body wall and what structure is ventral to this
ventral to the anorectal canal
genital tubercle
what happens to the genital tubercle in development
same in both sexes (initailly at least)
it grows and extends
the tip becomes the glans
the sides become the shaft of a developing phallus
what are the swellings at the side of the genital tubercle called
labioscrotal swelling
what happens to the enlargement of the phallus in females
stops enlarging early on and becomes the clitoris
what happens to the labioscrotal swelling in females
become labia major which engulf the whole of the vulva area
what happens to the urethral folds in females
form labia minora which encircles the urogenital sinus which forms the opening of the urethra and vagina
what happens to the enlargement of the phallus and urethral fold in males
continues to enlarge and incorporates the urethral fold on its lower surface
the urethra migrates along this fold towards the tip of the penis and the urethral fold zips up
what process and structures are responsible for penile erection
corpora spongiosa and cavernosa
when engorged with blood become hard
what drives the difference in male and female sexual development
testosterone
