Renal Clearance Flashcards
What is the basic functional unit of the kidney?
nephron
What is the role of the glomerulus?
filters blood
What is the role of the tubules?
reabsorbs water and filtered solutes
allows exchange of solutes to and from systemic circulation
What is the value for renal blood flow?
1200ml/min
-10% is filtered, so GFR=120ml/min
What are the functions of the kidney?
excretory
-filtration, secretion, reabsorption
endocrine
-renin, PGs, kinins, erythropoietin
metabolic
-vit D activtation, gluconeogenesis, insulin metabolism
renal function=excretion+endocrine+metabolic
Describe the excretory function of the kidney.
regulates fluid, electrolyte, and acid-base balance
removes metabolic waste products & foreign chemicals from blood for urinary excretion
Differentiate between the afferent arteriole and efferent arteriole.
afferent: brings blood to glomerulus
efferent: takes blood away from glomerulus
What composes the filtrate?
water, glucose, electrolytes, small molecules, amino acids, urea, uric acid, creatinine
excludes proteins and large molecules like RBC
What is the driving force that produces filtrate?
hydrostatic pressure
What is reabsorption?
movement of substances out of the renal tubule back into the blood capillaries
-prevents loss of substances needed by body
-water, solutes like ions, aa, glucose
What is secretion?
movement of substances out of the blood and into the renal tubules
-diffusion or active transport
What is the primary organ of parent drug or drug metabolite excretion?
kidney
What state must drug be in to be filtered by the kidney?
unbound drug
-all unbound drug is filtered by the kidney, whether drug is excreted depends on the PC nature of the drug
–>lipophilic drug is not excreted as can be reabsorbed from urinary filtrate
–>polar drugs are typically excreted
–>MW<2,000g/mole are filtered
What is the equation for renal clearance?
Clr=fu(b) x Clgfr + Clts - Cltr
If GF is the only Clr mechanism, what does this mean for extraction ratio?
low extraction ratio
extraction ratio=rate of extraction/rate of presentation
=GFR/RBF=120ml/min/1200ml/min=0.1
How do we know if TS is involved?
Clr>fu(b) x CLlgfr
What are the factors influencing glomerular filtration?
molecular size
plasma protein binding
glomerular integrity and total number of functioning nephrons
-diseases influence glomerular filtration
What are the markers of GFR?
inulin (exogenous)
creatinine (endogenous)
both are not bound to plasma proteins and undergo only glomerular filtration
Clr of these cpds serves as a measure of Clgfr and as a measure of renal function
When Clr is an important component of Cls, what is the relationship often seen between Clr and creatinine clearance?
proportional relationship between CrCl and Clr
What is the Intact Nephron Hypothesis?
loss of either glomerular or tubular function means loss of of whole nephron function
all-or-nothing
-all renal excretory processes decline in parallel
-loss of a functional nephron is reflected in GFR
-if GFR is 20% of normal, then Clr is 20% of normal
What is the result of active tubular secretion on Clr?
Clr to be greater than Clr due to GFR alone
What kind of drugs undergo active tubular secretion?
drugs that are charged, neutral, or lipophilic
Is tubular secretion saturable?
yes, alters Clr and no longer a constant
How much filtrate is formed per day?
180L
What kind of compounds undergo tubular reabsorption?
filtered endogenous compounds undergo active reabsorption (transporter-mediated)
-aa, fa, glucose, lactose, vitamins, minerals
filtered lipophilic drugs reabsorbed by passive diffusion (passive reabsorption)
-Clr minor elimination route
When do we infer passive reabsorption is occuring?
Clr<fu(b) x Clgfr
What are the physiological factors affecting TR?
urine concentration
-water reabsorption causes drug to concentrate in filtrate enhancing concentration gradient for passive reabsorption
urine flow
-affects Clr only for drugs that undergo extensive TR
-higher flow results in less TR (diuresis)
urine pH
-average is 6.3 but varies with time of day, diet, drugs
-pH partition hypothesis applies
What is the effect on TR and Clr on a weak organic acid if urine is acidic or basic?
acidic:
-TR increases
-Clr decreases
basic:
-TR decreases
-Clr increases
What is the effect on TR and Clr on a weak organic base if urine is acidic or basic?
acidic:
-TR decreases
-Clr increases
basic:
-TR increases
-Clr decreases
