Renal physiology 2 Flashcards
body composition female
45% solids
55% fluids
body composition male
40% solids
60% fluids
composition of total body fluid
2/3 intracellular fluid
1/3 extracellular fluid
composition of extracellular fluid
80% interstitial
20% plasma
why are there differences in body composition male and females
higher proportion of body fat in females
water Balance
what goes in must come out
amounts will vary significantly
regulated intake and output from thirst and ADH
gaining water
from drinking
from food via oxidative metabolism
how is water lost
expired gas saturated with water vapour e.g. breathing
sweat
hypotonic
body fluid can become hypertonic if you sweat a lot
why osmoregulate
changes in volume of ECF will change the osmolality
can affect size of cells due to changes in tonicity
tonicity
solutes effect on cells volume
what happens if the body fluid becomes hypotonic
cells will swell
kidneys excrete filter urine to restore homeostasis
what happens if the body fluid becomes hypertonic
cells shrink
kidneys excrete concentrated urine to restore homeostasis
osmolarity
number of particles in solution
usually referred to in comparison to another compartment
quantitive measure
central pontine myelinolysis
destruction of the myelin sheath in the pons
causes rapid osmotic changes
plasma osmolality
280-300 mOsm/kg-1 H2O
urine volume
0.5 – 18L/day-1
urine osmolality
1200-50 mOsm/kg-1 H2O
(normally 300-500 mOsm/kg-1 H2O )
what are plasma and urine osmolality and urine volume regulated by
ADH
from posterior pituitary
osmolality of ECF control
primarily controlled by regulating amount of water in the body
not NaCl
volume of ECf control
regulating NaCl in body
not water
osmoregulation dominates what
volume regulation
loop of henle
starts at the end of PCT and finishes at the macula densa
remaining 40-45% of filtrated isn’t handled by PCT
25-35% of Na+ and Cl-
salt and water reabsorption are separated
water passive in descending limb
salt is active in ascending limb
what is the main channel in the loop of henle used to absorb
Na+
K+
Cl-
NKCC loop of henle
Na+, K+ and 2Cl- enter
K+ removed
paracellular transport
purpose of the loop of henle counter current
maximise reabsorption of water and sodium
reabsorbed separately
as the ascending loop is impermeable to water
reabsorption in ascending loop affects the descending loop
counter current in LOH
- ascending limb NKCC
- interstitial osmolality increases
- descending limb surrounded by the same interstitium
- water moves out of the descending limb
- urine moves down the limb and ascends counter current to teach other
concentrated reaches thick ascending limb
NKCC does job
urine osmolality entering and leaving the loop
the same
why is loop anatomy crucial
limbs tightly packed together
change in interstitial osmolality in ascending limb directly affects the descending limb
urea reabsorption
in the collecting ducts
contributes to interstitial osmolality
what does reabsorption of solutes in the ascending limb do
increase interstitial osmolality
more water reabsorption in descending limb due to close proximity
urine osmolality increases down the limb as more water is reabsorbed
when urine travels up ascending limb there’s a lot of salt to reabsorb via NKCC
limbs/ urine move counter current
loop diuretics
furosemide
bumetanide
action of loop directs
act on NKCC to inhibit reabsorption of Na+, K+ and Cl-
increases osmolality in urine
reduced concentration gradient
less water reabsorbed by diffusion
diuresis and natriuresis
production of concentrated urine in presence of max ADH
isosmotic fluid enters proximal tubule
isosmotic reabsorption occurs
descending limb is highly permeable to water so water leaves by osmosis
until equilibrium of interstitial fluid
ascending thin limb permeable to solute so solute passively diffuses out
solute actively pumped out of thick ascending limb to maintain horizontal gradient as part of countercurrent mechanism
maintains corticomedullary osmotic gradient
early distal tubule impermeable to water so active dilution continues as NaCl is actively reabsorbed
later distal tubule and CD are permeable in ADH presence
water moves from tubule to intersittium by osmosis
drive by the osmotic pressure difference of fluid in tubule and interstitium
max ADH, small volume of high osmolarity urine is produced
reabsorbed water enters capillaries
returns to circulation
decreases plasma osmolarity
urea trapping/recycling
tubule impermeable to urea except in medulla
urea concentration increases as fluid flows along nephron and water reabsorbed
medullary collecting duct urea concentration and permeability is high
urea diffuses out of tubule down conc grad
into the medullary intersittium
increases osmolarity
Medullaryurea concentration increases (1)
Some urea diffuses into loop ofHenlein the medulla (2)
Urea trapped in tubule as fluid leaves loop ofHenle(3) and entersCD (4)
Urea recycles fromnephrontointerstitium, back tonephron
Urea accumulates inmedullaryinterstitiumto help maintaincortico-medullaryosmotic gradient (50% is excreted, 50% recycled)
Urea excretion is minimal when water needs to be conserved
distal convoluted tubule
macula densa to connecting segment
fine tuning of remaining Na+ and Cl-
sodium chloride co transporter
Na+/H+ and Cl-/HCO3- exchangers
no water reabsorption
NCCT
Also powered by Na⁺K⁺ATPase Blocked by thiazide diuretics e.g. bendroflumethiazide, indapamide
Na+/H+ exchanger
Na+ in
H+ out
Cl-/HCO3- exchanger
Cl- in
HCO3- out
H+ and HCO3-
H⁺ + HCO₃⁻ = H₂CO₃ ⇌ H₂O + CO₂
calcium reabsorption in DCT
10-15%
under influence of PTH and vitamin D
composition in DCT
low intracellular Na+
NCCT takes up the sodium
impermeable to water
filtrate leaving the DCT will become more dilute
main segments of the collecting duct
cortical
medullary
main functions of the collecting ducts
Potassium excretion and sodium reabsorption (ENaC and Na,K,ATPase) – principle cells
Acid-base handling – intercalated cells
Hormonal influence – aldosterone and ADH
Urea reabsorption via UT-A1 and UT-A3 (urea recycling)
intercalated and principle cells
potassium secretion
water reabsorption in the CD
Apical membrane (tubular side) is impermeable to water
BUT Permeabilitycan be increased
Insertion of aquaporins (water channels) into apical membrane
Under ADH influence
Basolateral surface is permeable
Water moves into the interstitium via osmosis
This osmotic gradient has been set up by the LoH countercurrent multiplier
action of ADH over hydration
Little/no ADH released
Few/no water channels inserted
Water channels are internalised into vesicles, away from membrane
Tubule impermeable to water
Water is lost in high flow-rate, dilute urine
action of ADH dehydration
ADH released from posterior pituitary
Insertion of water channels on apical membrane
Vesicles fuse with membrane
Water is reabsorbed back into the bloodstream
Small volume of concentrated urine lost
what is ADH regulated by
hypothalamic osmoreceptors in response to changes in plasma osmolarity
ADH release
cells swell or shrink
ADH synthesised and packaged into granules in neurons in hypothalamus
transported down the axon and stored and released from nerve terminals into the posterior pituitary
released into the blood stream
effect of plasma osmolality on ADH secretion
as plasma osmolality increases the ADH increases
rapidly
if <280 mOsm/kg (dilute) no ADH release
as plasma osmolarity increases
ADH secretion increases
Water channels insertedinto LDT & CD
Water reabsorbed byosmosis
Urine flow rate decreases
Urine osmolarity increases(removed water from it)
Plasma osmolaritydecreases back to normallimits
No change in total soluteexcretion
high osmolality, negative feedback
High plasma osmolality (egdehydration) detected by hypothalamic osmoreceptors
Secretion of ADH from posterior pituitary
Increased aquaporins in LDT & CD
Conservation of water by the kidney (concentrated urine)
Water reabsorbed back into blood
Reduction in plasma osmolality
low plasma osmolality negative feedback
Low plasma osmolality (egover-hydrated)
Less/no ADH
Less/no aquaporins in LDT and CD
Removal of water by the kidney (large volume, dilute urine)
Increase in plasma (and hence ECF) osmolality
nephrogenic diabetes insipidus
Non-response of ADH to V2 receptors
cranial diabetes insipidus
Reduced production of ADH
drugs used to target collecting ducts
Mineralocorticoid antagonists (MRAs) e.g. spironolactone, stop salt and water retention in the distal nephron drop in BP.
MRAs cause hyperkalaemia
over expression of ENaC
Liddle’s syndrome (Autosomal dominant cause of hypertension associated with hypokalaemia)
diabetes insipidus, cranial and ADH
Diabetes insipidus
Insufficient ADH secretion (cranial DI)
Idiopathic (characterised by degeneration of hypothalamic ADH secreting cells)
Caused by head trauma, infection or brain surgery
Familial (ADH gene mutation)
tment with synthetic ADH (Desmopressin)
failing to respond to ADH in NDI
Failure to respond to ADH (nephrogenic DI)
Kidney damage from certain drugs, or inherited
Dietary management, diuretics (to reduce GFR) and NSAIDS
Up to 18L/day urine output
alcohol and ADH
Inappropriately inhibits ADH
Beating a hangover
