Tubular Secretion Flashcards
What are organic anion transporters?
Antiporters responsible for transporting organic anions with a-KG
OAT1-3 transport OAs across the BL membrane
OAT4 transports OAs across the apical membrane
What is the role of Na-dicarboxylate transporter (NaDC)?
Symporter that uses the sodium concentration gradient to bring a-KG into the cell against its concentration gradient
a-KG is then used for OA transport via OATs
What transporters are responsible for transporting OAs into the tubular lumen?
OAT4 and MRP2
How do organic cations cross the basolateral membrane?
By either passive diffusion driven by the cell-negative potential difference (because it is against their concentration gradient)
Or by one of three uniporters (OCT1-3)
How do organic cations cross the apical membrane into the tubular fluid?
Via one of two OC-H antiporters (OCTN1-2) that exchange OCs by bringing H into the cell
MDR1 facilitates their diffusion across the apical membrane as well
Describe the specificity and transport rate for the active secretion mechanisms of organic anions and cations.
Both have relatively low specificity and a maximum transport rate
What is para-aminohippurate (PAH)?
Organic anion that is used for the measurement of effective renal plasma flow
Is filtered, but does not get reabsorbed
Excreted load = filtered load + secreted load
Why does PAH give a measurement of effective renal plasma flow instead of true RPF?
At low Ppah, the kidney removes only 90% of PAH from plasma because the other 10% goes to non-tubular renal tissue
Underestimates true RPF by about 10%
What is the extraction ratio?
The fraction of a substance which is removed form the plasma by the kidneys
E=(A-V)/A
A - concentration of substance in renal arterial plasma
V - concentration of substance in renal venous plasma
How can actual renal plasma flow be obtained?
By dividing the effective renal plasma flow by the extraction ratio
ERPF/Epah
What is bi-directional transport and what compound undergoes this process?
There are a few proximally secreted organic anions that undergo both active reabsorption and active secretion
Urate (uric acid)
How does the kidney handle urate?
Urate is freely filtered
90% is reabsorbed early in the PT
Active tubular secretion in late PT, followed by reabsorption again in the late PT
Net flux is primarily reabsorbtion
What four factors play a role in the production of hyperuricemia in gout?
Decreased filtration rate with maintained rubular reabsorption of urate
Increased reabsorption of urate
Decreased secretion of urate
Increased production of urate
How is potassium handled by the kidney?
Net reabsorption of filtered K, transport is bidirectional
87% of the filtered load is reabsorbed prior to the early distal tubule regardless of K in diet
The kidneys are the primary regulators of K balance
Describe the secretory process for K
The principal cell, when stimulated with aldosterone, will secrete K
The process is homeostatically regulated
How is K transported in the proximal tubule?
Both active and passive
Pump on the apical and BL membranes
Most K reabsorption in PT is normally passive
What are the determinates of K secretion in the distal tubule?
K concentration gradient between the principal cell and tubule fluid
Flow rate of tubule fluid
Electrical gradient across the luminal membrane of K secreting cells
Aldosterone
Describe how the K concentration gradient affects secretion in the principal cell
K secretion will increase when ICF [K] is high and/ore TF [K] is low
Describe how the flow rate of tubule fluid affects K secretion
Increased TF flow means the TF [K] is kept low, leading to increased secretion
SO, diruetics stimulate K secretion
How does the electrical gradient across the luminal membrane affect K secretion?
Na is positive, so its reabsorption causes the lumen to become more negative, driving K secretion
Poorly reabsorbed anions in the TF will maintain the lumen negative potential and promote K secretion
How does aldosterone affect K secretion?
Stimulates the secretion of K and H, and the reabsorption of Na
Increases the luminal Na and K channels and Na-K ATPase activity
What is the result of primary hypermineralocorticoidism?
Hypertension (increased Na reabsorption)
Hypokalemia (increased K secretion)
Metabolic alkalosis (increased K secretion)
What compounds primarily undergo passive reabsorption of secretion?
Non ionized forms of weak acids and bases
pH dependent
Urine is usually acidic, so most weak bases are charged and excreted
What happens to the secretion of organic anions in acidosis?
Urine becomes acidic, so weak acids are uncharged and move by diffusion i.e. are reabsorbed
What happens to the secretion of organic anions in alkalosis?
Urine becomes more alkaline and weak acids ionize, so their anions become trapped in the urine due to a decrease in permeability
Clincial relevance - aspirin poisoning, can alkalize the urine to trap the ionized form of aspirin and increase its excretion
