Tubular Reabsorption & Secretion Flashcards
1
Q
what is “electrical coupling” ?
what is an example of electric coupling seen in the nephron?
A
a means of transport in which two oppositely charged ions are moved together in a single direction such that charge is “balanced”
- generally does not involved a carrier
- ex: Na+ and Cl- reabsoprtion in the distal third of the proximal tubule
2
Q
what is “carrier coupling”
what are examples of carrier coupling in the nephron?
A
- means of transport in which two solutes occupy separate sites by a carrier
-
secondary active transport is a type of carrier coupling.
- in this example of carrier coupling, one solute is moved across the luminal membane by Na+ dependent transport along a Na+ concentration graident established by Na/K ATPase (on the basolateral membrane). here are two variations:
- co-transport (symport) - Na+ dependent solute is moved in the same direction as Na+
- example: glucose, phosphates, amino acids
- countertransport (antiport): Na+ dependent solute is moved in the opposite direction as Na+
- example: H+ (gets secreted)
- co-transport (symport) - Na+ dependent solute is moved in the same direction as Na+
- in this example of carrier coupling, one solute is moved across the luminal membane by Na+ dependent transport along a Na+ concentration graident established by Na/K ATPase (on the basolateral membrane). here are two variations:
3
Q
what is “osmotic coupling”?
- what type of regulation is does osmotic coupling permit?
A
- osmotic coupling: a movement of solutes that promotes subsequent water movement in the same direction
- by definition, this is an isotonic process
- volume regulation is contingent on osmotic coupling
- by definition, this is an isotonic process
4
Q
volume regulation vs osmoregulation
A
- volume regulation
- isotonic process: Na+ and water move together
- means by which we control blood pressure
- osmoregualtion
- not an isotonic process. a controlled Na+ gradient promotes movement of “free water” in the direction of higher osmolarity
- means by which we retain water
5
Q
explain the “generation of favorable of concentration gradients”
- which solutes create and utilize these favorable concentration gradients?
A
this involves the reabsorption of certain solutes (typically Na+) that water will then follow, causing the concentration of other solutes remaining in the tubule to increase
- generation of favorable concentration gradients is key to reabsoprtion of:
- urea
- chloride
- weak organic acids and bases
6
Q
discuss the reabsorbtion of urea along a “favorable concentration gradient”
- what creates this favorable concentration gradient?
- in what volume states is urea reabsorption especially high and why is this clinically relevant?
A
- in a hypovolemic state, sympathetic outflow is increased. this trigger the RAAS system (via B1 stiulation), increasing circulating Ang II.
- this increases Na+ and thus water reabsorption in the proximal tubule
- less water remains in the proximal tubule, so tubular concentration of urea increases significantly
-
urea is reaborbed along this gradient through leaky tight junctions in the PT
- this increases BUN (blood urea nitrogen)
- since creatinine (in a non pathological state) is neither absorbed/secreted, the BUN will go up relative to plasma creatinine, and the BUN:creatinine ratio (usually 10:1) will elevated
- ratio can rise up to 20:1
7
Q
discuss the BUN:creatinine ratio in preazotemia and renal failure
A
- prerenal azotemia = “pre-renal failure”
- this is defined by a sustained hypovolemic state
- the hypovolemic state causes urea reabsorption in the proximal tubule (by generation of a favorable gradient by Na+)
- creatinine not reabsorbed
- BUN:creatinine typically exist in the plasma at a 10:1 ratio
- enhanced reabsorption of urea in hypovolemic state increaess
- this is defined by a sustained hypovolemic state
- renal failure
- BUN increases
- plasma creatinine increases (due to glomerular damage)
- but BUN:creatinine ratio stays the same (10:1)
8
Q
“reabsorption of organic solutes”
- where and how does this occur
A
- this is a type of carrier-coupling seen only in the proximal tubule
- entails s_econdary active transport_ where
- Na+ reabsoprtion is coupled to organic solute reabsorption (primarily glucose)
- entails s_econdary active transport_ where
9
Q
Na/H antiporter in proximal tubule
- Discuss the role/regulation of this channel
A
- Na/H+ antiporter uses diffusion of Na+ down its concentration gradient to pump H+ in the ion against its [] gradient
- urine pH is acidic
- H+ in urine is accepteded by bases (HCO3, HPO4) to facilitate their reabsoprtion
- Na/H antiporter stimlated by angiotensin II and sympathetic stimulation in hypovolemic state
- this promotes Na+ reabsorption
10
Q
what happens happens when a solute’s filtered load exceeds its transport maximum?
A
this means that some solute that is typically reabsorbed will remain in the tubule and get excreted in the urine
11
Q
define renal threshold
A
this term applies to an organic solute that has a tubular maximum in the proximal tubule.
- renal threshold = plasma concentration of that solute at which the filtered load exceeds the reabsorptive capacity in the proximal tubule, and that solute ends up in the urine
- filtered load = GFR x Px
- so if GFR stays constant, increasing Px will increase filtered load
- filtered load = GFR x Px
12
Q
what substances have a have a tubular maximum?
- note the transporters these substances rely on when applicable
A
these are not all of the organic solutes reabosrbed in the PT, but they are the ones with a transport maximum.
- glucose - na-glucose symporters (SGLT-1 & SGLT-2)
- amino acids - by na-amino acid symporter
- phophate - by 2Na-phosphate symporter
- uric acid - by urate OH antiport & Na-H antiport
- ketone bodies
- vitamins
13
Q
discuss the tubular transport maximum (Tm) of glucose
- what is the Tm of glucose?
- what is the renal threshold of glucose?
- what happens when Tm is exceeded?
A
- under normal conditions, glucose freely fiiltered & entirely reabsorbed, meaning that there is no glucose in the urine.
- TmGlucose = 375 mg/min
- Tm = maximum filtered load = GFR x Pglucose
- assuming a normal GFR of 125 ml, the plasma concentration of glucose at which Tm is 375 (i.e., the renal threshold) = 300 mg/dl
- so, beyond a plasma concentration of 300 mg/dl, the saturated glucose symporters (SGLT-2 and SGLT-2) cannot increase absorptive rate, and glucose will start to appear in the urine
- this can progress to glucosuria: presence of glucose in the urine that increases urine osmolarity and draws water in. leads to increased urine volume –> increased excretion –> osmotic diuresis
- Tm = maximum filtered load = GFR x Pglucose
14
Q
what can cause glucosuria?
A
- glucosuria = presence of glucose in the urine
- diabetes mellitus: hyperglycemia elevates the plasma concentration of glucose beyond the renal threshold (300 mg) and thus beyond the maximum filtered load (tm)
-
renal glucosuria: reduced Tm (Tm drops below 375 mg/ml)
- reduced number of glucose carreries
- carriers have reduced affinity for glucose
15
Q
what is glizolin and what is it used to treat?
what are its market names?
A
- this is an SGLT-2 inhibitor
- inhibits glucose reabsorption in the proximal tubule, lowering blood glucose and inducing osmotic diuresis
- market names: Jardiance/Inokana
16
Q
discuss active secretion of organic solutes
- where does this occur
- what transport mechanisms are involved
A
like reabsorption of organic solutes, secretion of organic solutes occurs only in the proximal tubule
- secretion of organic cations:
- Na/K ATPase on basolateral membrane, by pumping K+ into the blood, creates a + charged plasma that favors diffusion of cations into the cell
- cations move across basolateral membrane via (OTCs) organic cation transporters
- these cations then move across the luminal membrane and into the filtrate via H+ antiporters
- secretion of organic anions:
- relies on recycling of a-ketoglutarate (aKG) across basolateral membrane
- a-KG moves into cell with 3 Na+
- a-KG then goes back into the bood in exchange for an organic anion that moves into the cell
- the organic ion then moves across the luminal membrane using OAT (organic anion transporters)
19
Q
discuss the movement of weak organic acids
- when their concentration gradients are “favorable”
- under acidic conditions
- in alkaline conditions
A
- a favorable gradient:
- established by reabsorption of Na+ and water, leaving acids & base [] high in filtrate
- this will promote reabsorption of both acids and/or bases dependent on pH status of filtrate
- established by reabsorption of Na+ and water, leaving acids & base [] high in filtrate
- an acidic filtrate (normal):
- most acids are nonionized (protonated) and get reabsorbed
- alkaline filtrate:
- most acids is ionized (deprotonated) and is stuck in the filtrate and excreted
20
Q
discuss the movement of weak organic bases
- when their concentration gradients are “favorable”
- under acidic conditions
- in alkaline conditions
A
- a favorable gradient:
- established by reabsorption of Na+ and water, leaving acids & base [] high in filtrate
- this will promote reabsorption of both acids and/or bases dependent on pH status of filtrate
- established by reabsorption of Na+ and water, leaving acids & base [] high in filtrate
- an acidic filtrate (normal):
- most bases are ionized (protonated), and get stuck in the filtate and excreted
- alkaline filtrate:
- most bases are nonionized (deprotonated), and get reabsorbed
