Kidney: Secretion Flashcards
the transfer of materials from the blood into tubular fluid
Tubular secretion
The secretion of ___ helps control blood pH
H+
Most secretion occurs in the ____ tubule with some in the more distal nephron
proximal
Endogenous substances (Prostaglandins) and exogenous diuretics (furosemide and bumetanide; thiazides) are delivered to sensitive distal sites after being secreted by the _____ _____
proximal tubules
Some organic molecules are not filtered to a great extent because they are extensively but reversibly bound to _____ ______
plasma proteins
As the blood flows out of the glomerulus past the proximal tubules, the free fraction of these organic ions in peritubular plasma are secreted into the filtrate via _____ (anions) and ____ (cations), reducing the concentration of free organic ion in the plasma and thereby causing most of the ion bound to plasma proteins to be “_______”
OATs
OCTs
unloaded
are two major classes of secretory transporters in the kidney
Organic anion transporters (OATs) and organic cation transporters (OCTs)
The transporters, ____, _____, and ____ in the renal basolateral membrane transport a large variety of endogenous and therapeutic compounds from the blood into the cells of the proximal tubules
OAT1, OAT3, and OCT2
Organic Ion Transporters in the renal epithelium are critical in _____ and _______ of xenobiotics from the systemic circulation, and therefore are major determinants of drug response and sensitivity
detoxification and elimination
Organic Ion Transporters control the exposure of renal cells to _____ drugs and environmental ____ and thus determine a patients susceptibility to drug-induced nephrotoxicity
nephrotoxic
toxins
Many medications or their metabolites exist as organic anions at physiological pH, and are transported by the multi-specific _____ _____ ____ of the kidney, liver, and choroid plexus
organic anion transporters (OAT)
the renal proximal tubule secretes clinically important pharmaceuticals such as
antibiotics
probenecid
loop and thiazide diuretics
angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and methotrexate, among others
the renal proximal tubule also transports various endogenous compounds, including
cyclic nucleotides prostaglandins folate neurotransmitter-metabolites hormone-conjugates
genetic variants in ____ are likely significant contributors to intersubject variability in drug response
OATs
Which of the following is an example of facilitated simple diffusion?
K channels
Which of the following is an example of primary active transport?
Na/K ATPase pump
H+ ATPase pump
Which of the following is an example of secondary active transport?
SGLUT1
Na/ H+ antiporter
Na+/amino acid symporter
Which of the following is an example of tertiary active transport?
OAT1
OAT3
Organic anion (OA) entry across the _______ membrane of the proximal tubule occurs through an antiporter (___ or ____) in exchange for dicarboxylate (especially, alpha-ketoglutarate, an intermediate in the Krebs cycle).
basolateral
OAT1 or OAT3
_________ is maintained at high intracellular concentrations by a Na-dicarboxylate cotransporter, which is driven by the trans-membrane Na gradient generated by the Na/K ATPase pump
alpha-ketoglutarate
OA secreted into the lumen by ____
OAT4
OAT3 gene expressed mainly in ______
Kidney
OAT4 is expressed in the ____ and ____
placenta and kidney
OATP8 is expressed in the _____ _____
fetal liver
_______ are critical for transport of many endogenous small organic cations and are critical for elimination of a wide array of drugs and environmental toxins.
Polyspecific organic cation transporters (OCTs)
OCT1 is expressed in the _____
liver
OCT2 is expressed in the ____
Kidney
In humans, about ___% of daily uric acid disposal occurs via the kidneys
70
urate is secreted and in unusual circumstances the rate of excretion may exceed the rate of _____
filtration
High blood levels of uric acid are associated with ____ and urate kidney ____
gout
stones
Urate crystal formation occurs best at ____ temperatures and tends to form most often in the hands and feet
lower
~90% of filtered ____ is reabsorbed
~10% is excreted in the urine
urate
filtered urate is both reabsorbed and secreted exclusively in the ______ tubule. Reabsorption occurs in S1 and S3. Secretion occurs in ____
proximal
S2
Substances That Decrease
Urate Excretion
Lactate Acetoacetate ß-Hydroxybutyrate Nicotinate Pyrazinamide (tuberculostatic)
Substances That Increase
Urate Excretion
Orotate Probenecid* Sulfinpyrazone* Benzbromarone* Losartan (antihypertensive drug) Tienilic acid (diuretic)*
______ is a uricosuric drug that increases uric acid excretion in the urine possibly by competing for OAT mediated reabsorption in the PCT
It is primarily used in treating gout and hyperuricemia
Probenecid
_________ competitively inhibits the renal excretion of some drugs {examples: penicillin, oseltamivir (Tamiflu)}, thereby increasing their plasma concentration and prolonging their effects
Probenecid
Urate reabsorption is a _____ active transport process
tertiary
Uricosuric drugs such as ______ and _____ act like orotate to compete with urate for transport through the urate/anion exchanger decreasing the reabsorption of urate
benzbromarone
probenecid
an ATP-dependent efflux pump with broad substrate specificity
P-glycoprotein (ABCB1)
_____ transports a broad spectrum of substrates across the cell membrane including psychotropic drugs
Mediates Digoxin uptake
ABCB1
Mediates the transport of compounds out of the brain across the blood-brain barrier and prevents the entry into the central nervous system of compounds such as ivermectin
ABCB1 transport
Effects the distribution and bioavailability of drugs and mediates the removal of toxic metabolites and xenobiotics from cells into urine, bile and the intestinal lumen
P-glycoprotein
______ intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein, thereby ______ the bioavailability which results in therapeutic plasma concentrations not being attained
Increased
reducing
Over-expression of ____ results in active cellular transport of anti-neoplastics and multidrug resistance
P-gp
supratherapeutic plasma concentrations and drug toxicity may result because of _____ P-glycoprotein expression or drug-drug interactions inhibiting PG activity
decreased
The two key genes of interest for warfarin response, which only explain about 15-30% of the variability in drug dose required to achieve the desired therapeutic response in different patients
cytochrome P450 2C9 gene, CYP2C9, and the vitamin K epoxide reductase complex 1 gene, VKORC1
Aldosterone acts on the ____ and ____
DCT & CD
______ medications are secreted more when urine is basic because _____ donate a proton and become negatively charged (anions) in basic fluids
____ medications are secreted more when urine is acidic because ____ receive a proton and become positively charged (cations) in acidic fluids
______ molecules are less likely to be reabsorbed
Acid
Acid
Basic
bases
Charged
