B5-045 Renal Physiology V Flashcards
what part of the tubule
- reabsorption of solutes/fluid
- secretion of organic anions/cations
proximal tubule
what part of the tubule
reabsorption of Na+, Cl-, K+
ascending loop of Henle
what part of the tubule
- reabsorption of Na+, Cl-, and water
- secretion of K+ and H+
2
distal tubule
collecting duct
[…] is required to drive all transporters in the proximal tubule
sodium
what part of the tubule
all transport depends on NaKATPase
proximal
what part of the tubule
glucose, amino acids, and phosphate are absorbed by apical Na+ cotransporters
proximal
what part of the tubule
protons are secreted by Na+ proton exhanger
proximal
what part of the tubule
chloride follows the paracellular pathway and base-dependent exchanges
proximal
what part of the tubule
organic anions are secreted by Na-dependent and independent OAT transporters
proximal
transport defects in the proximal tubule result in a kidney reabsorptive condition called
Fanconi syndrome
- polyuria, polydipsia, and dehydration
- hypophosphatemic rickets/osteomalacia
- growth failure
- metabolic acidosis
Fanconi
symptoms vary depending on extent
- hypokalemia
- hyperchrolemia
- hypophosphatemia, phosphaturia
- glucosuria, aminoaciduria
Fanconi
symptoms vary depending on extent
environmental causes of Fanconi syndrome
- heavy metals (lead)
- tetracyclins, gentamycin
- toluene (paint/dyes)
what part of tubule
Na+, K+ and Cl- are co-transported in the apical side by NKCC
ascending loop of Henle
what part of tubule
K+ and Cl- are absorbed together at the basolateral side or independently through channels
ascending loop of Henle
what part of tubule
K+ also leaks to the tubular side via ROMK1, helps with K+ recycling and maintains function of NKCC2
ascending loop of Henle
transport defects in the ascending loop of Henle depend on alterations in […], […], and […]
ROMK1
NKCC2
Barttin
Bartter’s syndrome
- polyuria, polydipsia
- poor muscle tone
- heart repolarization abnormalities
Bartter’s syndrome
- hyponatremia
- hypokalemia
- hypochloremia
- ECF volume contraction
- high renin aldosterone
- metabolic alkalosis
Bartter’s syndrome
environmental causes of Bartter’s syndrome
furosemide and bumetanide
inhibit NKCC2
malfunction of the countercurrent mechanism in Bartter’s syndrome causes
polyuria/polydipsia
malfunction of the NKCC, ROMK1, and Cl channels in Bartter’s syndrome causes
solute diuresis
wasting of Na+, K+, Cl-
malfunction of the juxtaglomerular apparatus in Bartter’s results in
hyper-reninemia, high aldosterone, alkalosis
activates proton pumps
hormone
aldosterone
treatment of Bartter’s
- postassium supplement
- aldosterone antagonists
- ACE inhibitors
- NSAIDs
- Ca+ and Mg+ supplements
- growth hormone
what part of tubule
Na+ and Cl- are cotransporterd in the apical side and reabsorped basolaterally
distal tubule
what part of tubule
K+ is secreted to the tubular fluid via K+ channels
distal
what part of tubule
Ca2+ is reabsorbed via channels and the basolateral Na/Ca exhanger
distal
transport defects in the distal tubule are due to mutations in […] or [..]
- TSC (Na/Cl exchanger)
- TRPM6 (magnesium)
- hyponatremia
- hypokalemia, high urine K+
- hypomagnesemia, high urine Mg+
- hypocalciuria
- ECF volume contraction
- normotensive
Gitelman’s syndrome
environmental cause of Gitelman’s
thiazide OD
what part of tubule
Na+ is reabsorbed apically by ENAc
collecting duct
what part of tubule
K+ is secreted to the tubular fluid via K+ channels
collecting duct
what part of tubule
water is reabsorbed via aquaporins
collecting tubule
transport defects in the collecting tubule are due to mutations in […] or […]
ENac (Liddle’s)
aquaporins (DI)
- increased ECF volume
- hypertension
- decreased renin-aldosterone
- hypokalemia
- metabolic alkalosis
Liddle’s syndrome
in Liddle’s syndrome, ENac is […]
sodium coming in all the time
constantly activated
water coming in, hypertension
- polyuria, polydipsia
- risk of dehydration
- dilute urine with low osmolarity
- sometimes hypernatremia
nephrogenic diabetes insipidus
environmental cause of nephrogenic diabetes insipidus
lithium
batteries
defects in proton secretion cause renal
acidosis
depending on transporter proximal or distal
in the proximal tubule, H+ is secreted by
transporter
Na/H exchanger
in distal and collecting tubules, H+ is secreted by
transporter
ATPases
- muscle weakness
- cardia repolarization problems
- growth retardation
- kidney stones
- hypokalemia
- hyperchloremia
- hypercalciuria
- metabolic acidosis
- low excretion of H+
proximal and distal renal tubular acidosis
- renal failure at early age (40-60)
- hematuria
- flank pain
- hypertension
adult polycystic kidney disease
- multiple kidney cysts
- liver
- aneurisms
adult polycystic kidney disease
mutations in PKD1 and PKD2 cause
adult polycystic kidney disease
protein: polycystin
mutations in PKHD cause
child polycystic kidney disease
protein: fibrocystin
chracterized by the growth of multiple fluid filled cysts that affect kidney structure and function
autosomal dominant polycystic kidney disease
responsible for 10% of all cases of ESRD
autosomal dominant polycystic kidney disease
[…] control normal kidney developent and function via Ca and cAMP
polycystins
polycystin alterations cause
autosomal dominant polycystic kidney disease
- hematuria
- hypertension
- ESRD
autosomal dominant polycystic kidney disease
best imaging modality for autosomal dominant polycystic kidney disease
US or MRI
treatment of autosomal dominant polycystic kidney disease
hypertension, pain mangement
inhibit cAMP and ADH
will cause polyuria though
salt wasting due to malfunction of NKCC causes hypokalemia
disease
Bartter’s
characterized by mutations in ENaC
disease
Liddle’s
hyperactivity of ENac increases sodium reabsorption causing water retention and high blood pressure
Liddle’s
mutations of Na/Cl co transport in the distal tubule
Gitelman’s
characterized by low FENa
Liddle’s
Furosemide OD will present similar to what syndrome?
Bartter’s
increase in renin due to malfunction of the NKCC in macula densa
Bartter’s
causes secondary hyperaldosteronism
how does high aldosterone lead to an increase in blood pH?
- aldosterone stimulates the proton ATPasese in the distal and collecting tubule
- more H+ release via kidneys –> metabolic alkalosis
causes metabolic acidosis due to the inability to secret protons and acidify the urine below 5.5
renal distal tubular acidosis
(Type 1)
polycystic kidney disease also present with cysts in the
liver
which diuretic is the most effective treatment of Liddle’s?
triamtrene
medications that inhibits ENac
triamterene
what medication targets carbonic anhydrase?
acetazolamide
what medication inhibits NKCC in the loop of Henle
furosemide
what medications block Na/Cl transport in the distal tubule?
thiazides
generalized reabsorption defect in PCT causing increased secretion of amino acids, glucose, bicarb, and phosphate
Fanconi
- causes metabolic acidosis (proximal RTA)
- hypophosphatemia
- hypokalemia
Fanconi
- growth retardation and rickets/osteopenia are common due to hypophosphatemia
- volume depletion also common
Fanconi
- reabsorption defect in the ascending loop of Henle
- affects NKCC transporter
Bartter
- metabolic alkalosis
- hypokalemia
- hypercalciuria
Bartter
present similarly to chronic loop diuretic use
Bartters
reabsorption defect of NaCl in DCT
Gitelman
- metabolic alkalosis
- hypomagnesemia
- hypokalemia
- hypocalciuria
Gitelman
presents similarly to chronic thiazide diuretic use
Gitelman
less severe than Bartter
GOF mutation causing decreased Na+ channel degradation leading to increased Na+ reabsorption in collecting tubules
Liddle
- metabolic alkalosis
- hypokalemia
- hypertension
- decreased aldosterone
Liddle
presents similarily to hyperaldosteronism but aldosterone is nearly indectable
Liddle
treatment for Liddle
amiloride or triametere
(ENac inhibitors)
