renal Flashcards
Total body water
60% of weight, average of 42L but more in younger people.
25-30% intracellular
38% ECF
ICF and ECF ions
ICF - K+ = 148mM , Na+ = 10mM, Cl- = 4mM, proteins = 55mM
ECF -K+ = 5mM , Na+ = 140mM, Cl- = 103mM, proteins = 15mM
Na role and how we obtain it
input by diet av. 150mM a day, lose 140mM in urine and 10mM i sweat and stool
if not excretion increase in Na+ leads to increase h20 reabsorption to increase BP
Kidney structure ;
150g, 12th thoracic to 3rd lumbar, 10cm tall, 5.5 cm wide
cortex - outer layer, paler
medulla - inner layer, dark, medullary rays, striated
capsule - fibroule for protection
nephron - functional unit 1-1.5million per kidney
2 types of nephron>
superficial - glomerolus dlose to cortec surface, and Lof H in outer medulla
Juxtamedullary - henle is in inner medulla too , key in urine concentration
renal faliure -
drop in GFR leads to increase serum urea and creatine
progressive thickening of the glomerular membrane so filtration is slowed damage and scarring as inflammation so reduced renal size and fibrosis occurs.
causes - diabetes, hypertension, polycystic kidney
Treat - diuretics, Na bicarbonate to reduce acidosis and change diet
in US RF kidney small and bright
uraemia symptoms -
hypertension acidosis as cannot excrete salt and water vomiting protein in urine pericarditis
Bowmans capsule -
20 % plasma into bowman the rest goes back into circulation via the renal vein. blood cells and protein remain apart from 1% (albumin)
types of transport across renal cells
paracellular - between tight junctions
transcellular - through cell via exocytosis and endocytosis
Proximal tubule reabsorption -
reabsorb 70% of filtrate
70% water and Na+
100% glucose and amino acids
90% HCO3-
Porximal tubule cell
rich in mitochondria for ATP, high SA
Na+/K+ ATPase so 3Na+ out and to K+in on baso
multiple sodium coupled transporters eg.
SGLT1 - sodium glucose protein
NaPi2 - sodium and phosphate transport
NHE3 - sodium and hydrogen exchanger so H leaves and bind to form HCO3- that dissociates into CO2 and H2O t move into cell and then H+ is recycled and HCO3-leaves cell to maintain ph of blood
NHE3 knock out in mice causes -
Ph to drop so BP drop as less H20 reabsorbed
isosmotic meaning
loss of ions followed by h20 via aquaporins
Familial Renal Glycosuria -
increase glucose in urine if SGLT1 and 2 are lost
more glucose in plasma the mor is reabsorbed until blood is saturated around 375mg/min so then in urine
Loop of hence role ;
reabsorb Na+,cl-,h2o,ca2+mg2+
thin descending = loss of H20 yet impermeable to Na+ and CL- so osmotic gradient to h20 to leave into interstitial
thin ascending = permeable to cl- and Na+ but imp to h20
thick ascending = same as thin
CLCK and barttin role in TAL
on basolateral of cell, CLCK removes Cl - and barttin is the accessory protein. I not there none reabsorbed
e.g. in barrtinns syndrome
ROMK role in TAL
recycle K+ out of cell for NKCC2 to work
NKCC2 role in TAL
transports Na+, 2Cl- and K+ int the TAL cell so Na + can be removed on baso into the blood and CL-
too much cl- stops it from working
Bartters sysndrone
recessive mutation , loss of salt in urine so polyuria (increase flow) low BP and Hypokaleamia as K lost in urine, not as much calcium reabsorbed so clarification in kidney = stones
if ROMK,NKCC2 or CLCK bartin are mutated
Loop diuretics :
eg. furosemide and bumetamide - treat high BP as block NKCC2 so loose H20 as little ions reabsorbed
Early distal tubule reabsorption -
Na+, cl- and mg2+
NCC - Na and Cl transporter on apical Mg cahnnels on apical not known how lost on baso Na/K atpase on baso K+ lost out of baso through channel CLCK and Barttin - lose CL- into blood
Gitelmanns syndrome
recessive, loss of salt, polyuria, hypotension, hypokalaemia, alkalosis as NCC mutation
thiazide diuretics -
inhibit the NCC in early distal tubule
2 cell types in distal tubule
prinicpal and intercalated (alpha and beta)
Principal cell
ENaC - Na+ channel which is regulated by phosphrylation
ROMK - K+ out of apical, secreted into tubular fluid
The more Na+ in the more K+ out , Na+ drives ROMK
Aquaporin 2 - H20 into apical and out via AQP2,3
Diabetes insipidus cause
if AQP2 in principle cell mutated
Liddles syndrome
autosomal dominant, high blood pressure associated with low plasma renin activity, metabolic alkalosis, low blood potassium as increased activity of ENaK in principal cell
Amiloride Diuretics -
block ENaK in Principal cell , treats high BP
Alpha IC cell role in distal tubule
H+ secretion & HCO3- reabsorption
AE1 - BASOLATERAL SIDE - HCO3- out and Cl- in to regulate Ph
Cl- is pumped out by own channel to continue to allow HCO3- to b pumped out, it is recycled
H+ into tubular fluid by atpase pump
make blood more alkali
Beta IC cell role in distal tubule
HCO3- secretion and H+ reabsorption
AE1 on apical membrane - HCO3- out and Cl- inCl- is pumped out by own channel to continue to allow HCO3- to b pumped out, it is recycled
H+ into blood by atpase pump
make blood more acidic
Distal renal tubular acidosis
mutation in AE1 so pH drops
Medullary collecting duct permeability:
low Na+ permeability but high H20 and urea in presence of vasopressin
Hypovolamia :
low GFR so high BP
Hyperkalaemia
lack of K+ secretion so cardiac excitability - increase arrhythmia
Vasopressin -
posterior pituitary
regulates body fluid, conserve H20
osmoreceptor in hypothalamus sensitive to chance by 1%
If plasma osmolarity high - release vasopressin, thirsty
can increase due to high salt in food, drugs, stress
Acts on AQP2 in principal cells, binds to V2 receptor on basolateral, activates protiein kinase A, phosphorylates proteins on vesicle with AQP2 so fuse with membrane and increase of channels in the apical
if Vasopressin low, channels back to vesicle s
Aldosterone -
adrenal glads in zona glomerulosa the outermost layer
a mineralocorticoid, regulates plasma Na+ and K+ volume
Released if K+ is high
acts on DT and CD causes Na+ reabsorption so k+ secreted
is a steroid hormone so cytosolic receptor as diffuses into cell
receptor stimulates RNA transcription of ENaC
Renin -
in juxtaglomerular apparatus, released if low ECF volume. Causes angiotensin 1 to convert to 2 which is the acvtive form that causes the release of aldosterone and vasoconstriction to increase BP
