Tubular Reabsorption & Secretion Flashcards
what is “electrical coupling” ?
what is an example of electric coupling seen in the nephron?
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
what is “carrier coupling”
what are examples of carrier coupling in the nephron?
- 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:
what is “osmotic coupling”?
- what type of regulation is does osmotic coupling permit?
- 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
volume regulation vs osmoregulation
- 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
explain the “generation of favorable of concentration gradients”
- which solutes create and utilize these favorable concentration gradients?
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
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?
- 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
discuss the BUN:creatinine ratio in preazotemia and renal failure
- 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)
“reabsorption of organic solutes”
- where and how does this occur
- 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
Na/H antiporter in proximal tubule
- Discuss the role/regulation of this channel
- 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
what happens happens when a solute’s filtered load exceeds its transport maximum?
this means that some solute that is typically reabsorbed will remain in the tubule and get excreted in the urine
define renal threshold
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
what substances have a have a tubular maximum?
- note the transporters these substances rely on when applicable
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
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?
- 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
what can cause glucosuria?
- 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
what is glizolin and what is it used to treat?
what are its market names?
- this is an SGLT-2 inhibitor
- inhibits glucose reabsorption in the proximal tubule, lowering blood glucose and inducing osmotic diuresis
- market names: Jardiance/Inokana
discuss active secretion of organic solutes
- where does this occur
- what transport mechanisms are involved
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)
what is diffusion trapping?
- the mechanism by which the ionized form of an acid or base cannot diffuse across a membrane. ionized molecules are charged and thus not lipid soluble
- ionized acid = not protonated (A-)
- ionized base = protonated (BH2+)
what is normal urine pH?
how does this dictate weak acid and base movement during udner normal conditions?
normal urine pH = 6 (slightly acidic)
- acids tend to be protonated (non-ionized), thus lipid lipid soluble, and get reabsorbed
- bases tend to be protonated (ionized), thus lipid insoluble, and are stuck in the tubules –> get excreted
- bases are diffusion trapped
discuss the movement of weak organic acids
- when their concentration gradients are “favorable”
- under acidic conditions
- in alkaline conditions
- 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
discuss the movement of weak organic bases
- when their concentration gradients are “favorable”
- under acidic conditions
- in alkaline conditions
- 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
what volume state would increase reabsorption of acids and bases?
a hypovolemic state (GFR and tubular flow decrease, allowing time for reabsorption)
how we faciliate organic acid secretion and organic acid reabosprtion by manipulating the filtrate?
the excretion of organic acids is facilitated by making the tubular filtrate more alkaline, and reabsorption is enhanced by making the filtrate more acidic.
how can we faciliate the excretion/reabsorption of bases by manipulating the filtrate?
excretion of organic bases is facilitated by increasing tubular acidity, and reabsorption is enhanced by making the tubular fluid more alkaline.
