Transport Mechanisms 2 Flashcards
effect of loops diuretics (furosemide) on ascending limb of LOH
- inhibits Na/K/2Cl transporter
- increases urination
result of inhibition of Na/K/2Cl transporter in LOH
- decreased K+ and Ca2+ reabsorption
aka hypokalemia (and alkalosis) and hypocalcemia
how do we have decreased Ca2+ with decreased K+
- electrochemical gradient that is usually formed by the back leak of K+ will lead to paracellular Ca2+ transport
- that has now been lost
Bartter’s syndrome affects what part of the kindey
- ascending limb of LOH
cause of Bartter’s syndrome
- defect in Na/K/2Cl transporter
genetics of Bartter’s syndrome
- autosomal recessive
symptoms of Bartter’s syndrome
- hypokalemia
- metabolic alkalosis
- polyuria
- polydipsia
- dehydration
- high urine calcium
what transporter does the early distal tubule have
result
- Na/Cl cotransporter (NCC)
- dilutes tubular fluid
epithelium in early distal tubule
result
- tight epithelial
- transcellular Na+ movement via the Na/Cl cotransporter
- impermeable to H20
how much Na is reabsorbed in the early distal tubule
- 5-10%
what transporter is located in the late distal tubule/cortical collecting duct
- epithelial Na Channel (ENaC)
- alpha intercalated cells
what is the epithelial Na Channel dependent on
- aldosterone
result of epithelial Na channel
- Na enters cell down chemical gradient through ENaC
- creates negative electrical potential
- results in K+ secretion into tubular lumen
result of alpha intercalated cells
result of beta intercalated cell
- H+ secretion into tubular lumen
- HCO3/Cl- ATPase
- HCO3 extruded into the lumen
H+ secretion into tubular lumen through what mechanisms
- H+ ATPase
- H/K ATPase
what happens with the secreted H+ in late distal tubule
what happens with HCO3- in the late distal tubule
- binds to NH3 and other buffers
- results in HCO3 reabsorption into blood through HCO3/Cl- exchanger
result of the thiazide diuretics such as hydrochlorothiazide and chlorthalidone
- inhibit the Na/Cl cotransporter in the early distal tubule
result of amiloride/triamterene
what are they also referred to as
- inhibit epithelial sodium channel
- K+ sparing diuretics
why are amiloride/triamterene referred to as K+ sparing diuretics
- they do not promote K+ secretion
we generally use amiloride/triamterene in combination with
- thiazide or loop diuretic
cause of Gitelman’s
result
- loss of function of Na/Cl cotransporter
- increased surface expression of K in collecting duct
- Na+ loss into urine
Gitelman’s acts like what
- a thiazide diuretic
symptoms of Gitelman’s
- hypokalemia - loss of K+ in the urine
- metabolic alkalosis
- salt craving
cause of pseudohypoaldosteronism II
result
- gain of function of Na/Cl cotransporter
- increases Na and Cl reabsorption
- decreases surface expression of K channels in collecting duct.
symptoms of pseudohypoaldosteronism II
- hypertension - increase Na reabsorption
- hyperkalemia - potassium cannot be secreted into the urine
- Metabolic Acidosis
renin and aldosterone levels in pseudohypoaldosteronism II
- low
- you’re having high BP so you have increased perfusion and don’t need the RAAS system
cause of Liddle’s
result
- gain of function in epithelial Na channel
- uncontrolled Na retention in blood
symptoms of Liddle’s
- hypertension - increase Na+ reabsorption
- hypokalemia - you have reabsorbed all this sodium which creates an even greater gradient for K+ secretion so your K+ in blood is less.
- metabolic alkalosis
cause of pseudohypoaldosteronism type I
- loss of function of epithelial Na channel
symptoms of pseudohypoaldosteronism type I
- hypovolemia
- metabolic acidosis
- sodium wasting
- hyperkalemia
- hyponatremia
aldosterone levels in pseudohypoaldosteronism type I
- elevated due to hypovolemia
cause of distal RTA type I
- impaired H+ secretion
distal RTA type I impaired H+ secretion leads to
- non-anion gap acidosis
- low bicarb
- hypokalemia
- cannot acidify urine
most common cause of distal RTA type I
- diminished H+ ATPase activity
less common causes of distal RTA type I
- increased lumenal membrane permeability leading to backleak of H+
- diminished activity of H+/K+/ATPase
signs of hyperkalemic RTA type 4
- hyperkalemia
- mild non-anion gap metabolic acidosis
cause of hyperkalemic RTA type 4
result
- hypoaldosteronism due to a true deficiency or resistance
- decreased Na+ reabsorption and less K+ secretion
syndrome of apparent mineralocorticoid excess (SAME) cause
-deficiency in enzyme that converts cortisol to cortisone
what binds the mineralcorticoid receptor
- cortisol
plasma cortisol concentration compared to aldosterone in syndrome of apparent mineralocorticoid excess (SAME) cause
- 100x higher
- basically still acts like aldosterone
blood pressure in syndrome of apparent mineralocorticoid excess (SAME)
- hypertension
potassium levels in syndrome of apparent mineralocorticoid excess (SAME)
- hypokalemia due to K+ secretion
acidosis/alkalosis in syndrome of apparent mineralocorticoid excess (SAME)
- metabolic alkalosis - hydrogen ion secretion
- ACTS LIKE ALDOSTERONE WHICH CAUSES H+ SECRETION
plasma renin activity in syndrome of apparent mineralocorticoid excess (SAME)
- low
plasma aldosterone concentration in syndrome of apparent mineralocorticoid excess (SAME)
- low
what hormones regulate in the early distal tubule
- none
what hormones regulate in the late distal tubule and cortical collecting duct - principal cells
- aldosterone
- ADH
- ANP
what hormones regulate in the late distal tubule and cortical collecting duct - intercalated cells
- aldosterone
role of aldosterone in the late distal tubule and cortical collecting duct - principal cells
- binds to intracellular receptor
- stimulates insertion of epithelial Na channel and K channels in luminal membrane
role of ADH in the late distal tubule and cortical collecting duct - principal cells
- binds to V2 receptor in basolateral membrane
- V2 receptor activates adenylate cyclase to convert ATP -> cAMP to activate PKA
- phosphorylation of aquaporin 2 causes shuttling and stimulates insertion of aquaporin 2 in luminal membrane
role of ANP in the late distal tubule and cortical collecting duct - principal cells
- inhibits aldosterone effects
role of aldosterone late distal tubule and cortical collecting duct - intercalated cells
- stimulates H+ ATPase activity
hormonal regulation in the medullary collecting duct
- ADH dependent water reabsorption
- ADH dependent urea reabsoprtion
- aldosterone dependent Na+ reabsorption and K+ secretion
RAAS during hypovolemia
- decreased distal delivery of NaCl to macula densa
- increased renin release by JG cells
- increase in angiotensin II to maintain GFR
H2O enter lumen via which aquaporin and enters how
- 2
- enters along osmotic gradient
H2O leaves via which aquaporin
- 3
importance of aquaporin 3
- constitutively expressed
- not ADH regulated
what does high urine osmolarity reflect about ADH and urine volume
- ADH present
- water reabsorbed
- low urine volume
what does low urine osmolarity reflect about ADH and urine volume
- ADH not present
- water not reabsorbed
- high urine volume
the V2 receptor also activates which other transporter
where is this transporter expressed
- urea transporter
- expressed in medullary collecting duct
urea is reabsorbed where and how
- across luminal membrane through UT1
- along a concentration gradient
urea exits where and how
- exits basolateral membrane through UT3
what is the location of AQP2 and AQP3
- distal tubule
- cortical and medullary collecting duct
which AQP is located on the apical membrane
- 2
which AQP is located on the basolateral membrane
- 3
ANP is released in response to
- atrial volume
result of ANP
- enhances Na+ excretion
- counters effects of RAAS
- relax vascular smooth muscle
- vasodilator
- increase diuresis
