Kidney: Secretion

Question 1

the transfer of materials from the blood into tubular fluid

Answer 1

Tubular secretion

Question 2

The secretion of ___ helps control blood pH

Answer 2

H+

Question 3

Most secretion occurs in the ____ tubule with some in the more distal nephron

Answer 3

proximal

Question 4

Endogenous substances (Prostaglandins) and exogenous diuretics (furosemide and bumetanide; thiazides) are delivered to sensitive distal sites after being secreted by the _____ _____

Answer 4

proximal tubules

Question 5

Some organic molecules are not filtered to a great extent because they are extensively but reversibly bound to _____ ______

Answer 5

plasma proteins

Question 6

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 “_______”

Answer 6

OATs
OCTs
unloaded

Question 7

are two major classes of secretory transporters in the kidney

Answer 7

Organic anion transporters (OATs) and organic cation transporters (OCTs)

Question 8

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

Answer 8

OAT1, OAT3, and OCT2

Question 9

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

Answer 9

detoxification and elimination

Question 10

Organic Ion Transporters control the exposure of renal cells to _____ drugs and environmental ____ and thus determine a patients susceptibility to drug-induced nephrotoxicity

Answer 10

nephrotoxic

toxins

Question 11

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

Answer 11

organic anion transporters (OAT)

Question 12

the renal proximal tubule secretes clinically important pharmaceuticals such as

Answer 12

antibiotics
probenecid
loop and thiazide diuretics
angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and methotrexate, among others

Question 13

the renal proximal tubule also transports various endogenous compounds, including

Answer 13

cyclic nucleotides
prostaglandins
folate
neurotransmitter-metabolites
hormone-conjugates

Question 14

genetic variants in ____ are likely significant contributors to intersubject variability in drug response

Answer 14

OATs

Question 15

Which of the following is an example of facilitated simple diffusion?

Answer 15

K channels

Question 16

Which of the following is an example of primary active transport?

Answer 16

Na/K ATPase pump

H+ ATPase pump

Question 17

Which of the following is an example of secondary active transport?

Answer 17

SGLUT1
Na/ H+ antiporter
Na+/amino acid symporter

Question 18

Which of the following is an example of tertiary active transport?

Answer 18

OAT1

OAT3

Question 19

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).

Answer 19

basolateral

OAT1 or OAT3

Question 20

_________ 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

Answer 20

alpha-ketoglutarate

Question 21

OA secreted into the lumen by ____

Answer 21

OAT4

Question 22

OAT3 gene expressed mainly in ______

Answer 22

Kidney

Question 23

OAT4 is expressed in the ____ and ____

Answer 23

placenta and kidney

Question 24

OATP8 is expressed in the _____ _____

Answer 24

fetal liver

Question 25

_______ are critical for transport of many endogenous small organic cations and are critical for elimination of a wide array of drugs and environmental toxins.

Answer 25

Polyspecific organic cation transporters (OCTs)

Question 26

OCT1 is expressed in the _____

Answer 26

liver

Question 27

OCT2 is expressed in the ____

Answer 27

Kidney

Question 28

In humans, about ___% of daily uric acid disposal occurs via the kidneys

Answer 28

70

Question 29

urate is secreted and in unusual circumstances the rate of excretion may exceed the rate of _____

Answer 29

filtration

Question 30

High blood levels of uric acid are associated with ____ and urate kidney ____

Answer 30

gout | stones

Question 31

Urate crystal formation occurs best at ____ temperatures and tends to form most often in the hands and feet

Answer 31

lower

Question 32

~90% of filtered ____ is reabsorbed | ~10% is excreted in the urine

Answer 32

urate

Question 33

filtered urate is both reabsorbed and secreted exclusively in the ______ tubule. Reabsorption occurs in S1 and S3. Secretion occurs in ____

Answer 33

proximal | S2

Question 34

Substances That Decrease | Urate Excretion

Answer 34

``` Lactate Acetoacetate ß-Hydroxybutyrate Nicotinate Pyrazinamide (tuberculostatic) ```

Question 35

Substances That Increase | Urate Excretion

Answer 35

``` Orotate Probenecid* Sulfinpyrazone* Benzbromarone* Losartan (antihypertensive drug) Tienilic acid (diuretic)* ```

Question 36

______ 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

Answer 36

Probenecid

Question 37

_________ competitively inhibits the renal excretion of some drugs {examples: penicillin, oseltamivir (Tamiflu)}, thereby increasing their plasma concentration and prolonging their effects

Answer 37

Probenecid

Question 38

Urate reabsorption is a _____ active transport process

Answer 38

tertiary

Question 39

Uricosuric drugs such as ______ and _____ act like orotate to compete with urate for transport through the urate/anion exchanger decreasing the reabsorption of urate

Answer 39

benzbromarone | probenecid

Question 40

an ATP-dependent efflux pump with broad substrate specificity

Answer 40

P-glycoprotein (ABCB1)

Question 41

_____ transports a broad spectrum of substrates across the cell membrane including psychotropic drugs Mediates Digoxin uptake

Answer 41

ABCB1

Question 42

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

Answer 42

ABCB1 transport

Question 43

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

Answer 43

P-glycoprotein

Question 44

______ 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

Answer 44

Increased | reducing

Question 45

Over-expression of ____ results in active cellular transport of anti-neoplastics and multidrug resistance

Answer 45

P-gp

Question 46

supratherapeutic plasma concentrations and drug toxicity may result because of _____ P-glycoprotein expression or drug-drug interactions inhibiting PG activity

Answer 46

decreased

Question 47

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

Answer 47

cytochrome P450 2C9 gene, CYP2C9, and the vitamin K epoxide reductase complex 1 gene, VKORC1

Question 48

Aldosterone acts on the ____ and ____

Answer 48

DCT & CD

Question 49

______ 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

Answer 49

Acid Acid Basic bases Charged