Renal Clearance and Tubular Function Flashcards
What is renal clearance?
The volume of plasma from which that a substance is completely cleared, by the kidney per unit time (mL/min). Denoted Cx
Cx =?
Cx = (Ux*V)/ Px
Ux: urine concentration of x (mg/mL)
V: urine volume (mL)
Px: Plasma concentration of x (mg/mL)
What condition must be met to estimate GFR using renal clearance?
Mass of urine (Uw) excreted per unit time = Mass of urine filtered (Uw) per unit time
GFR =?
GFR = (Uw*V)/Pw
Uw: mass of urine
V: volume of urine
Pw: Plasma concentration of w
GFR = (Uw*V)/Pw is only true if “w” is ______? (5)
- Freely filterable at the renal corpuscle
- Not reabsorbed
- Not secreted
- Not synthesized by tubules
- Not broken down by tubules
What is inulin?
A polysaccharide that is completely cleared from the kidney, so it can be used to determine GFR; not made endogenously, so it must be administered to measure clearance
Clearance of Inulin (Cin) = GFR
What is creatinine?
An inert product of protein metabolism that is freely filterable and not reabsorbed by the kidney; measuring clearance of creatinine can determine GFR, but it is slightly higher than the actual value due to a small amount of creatinine being secreted
What is a normal plasma creatinine level? What would happen to creatinine levels if GFR decreased by 50%?
10 mg/L
Increases then stabilizes at 20 mg/L; indicates renal function (especially GFR) is impaired
What is PAH?
Para-aminohippurate
IV medication used to measure GFR; not reabsorbed and almost totally secreted
Approximates renal plasma flow
CPAH =?
CPAH = UPAHV/PPAH = ERPF
CPAH: Clearance of PAH
UPAH: urine concentration of PAH
V: volume
PPAH: Plasma concentration of PAH
ERPF: effective renal plasma flow
Why does clearance of PAH only approximate effective renal blood flow?
10-15% of total renal plasma flow supplies non-filtering and non-secreting portions of the kidneys (ie. peripelvic fat), which cannot lose PAH by secretion
Describe diffusion
Movement of charged or uncharged solutes down its concentration gradient
Diffusion of ions is affected by electrical potential differences across cell membranes of the renal tubules
Describe facilitated diffusion
Solutes move down their concentration gradients with the help of transport proteins in the cell membrane
Describe primary active transport
Movement of molecules through a mechanism which is directly coupled to ATP consumption, going against a solute’s concentration gradient
Describe secondary active transport
Energy from downhill movement of solute provides energy for the uphill movement of another solute
Describe solvent drag
Occurs when water is reabsorbed and solutes follow behind (movement of nutrients across capillaries)
What are the two potential routes for reabsorptive movement from lumen to interstitium?
Paracellular
Transcellular
What is paracellular reabsorption?
Movement of solutes between cells (i.e. across tight junctions); can be by diffusion or solvent drag
What is transcellular reabsorption?
Reabsorption of substances that must cross two plasma membranes between the tubular lumen and the interstitial fluid
Ex: lipid-soluble substances (by diffusion and net passive reabsorption)
What are the two criteria for transcellular transport?
- One of the transporters MUST be active
- The transporter used at the luminal membrane must be different from the one on the basolateral membrane
What is a transport maximum?
Tm
Amount of material that can be transported across a membrane per unit time (when all transporters are fully saturated); reflects the maximal transport capacity of BOTH kidneys
What is renal threshold?
The plasma concentration where a substances first beings to appear in the urine; this begins when Tm is almost reached
Describe the concept behind bidirectional transport. What part of the nephron does this typically occur?
Secretion creates a concentration of substances X higher in the lumen than in the ISF, which favors paracellular reabsorption
Reabsorption establishes a concentration lower in the lumen than in the ISF, which favors passive paracellular secretion
Typically occurs in the proximal tubule
Is reabsorption of sodium active or passive? Transcellular or paracellular?
Active
Transcellular
Is reabsorption of chloride passive or active? Paracellular or transcellular?
Passive (paracellular diffusion)
Active (transcellular)
*directly or indirectly coupled with sodium reabsorption*
What substances of a filtered load are almost completely reabsorbed? (6)
Water (99.2%)
Na+ (99.4%)
Ca2+ (98.2%)
HCO3- (99.9%)
Cl- (99.2%)
Glucose (100%)
Why is K+ only 86.1% reabsorbed by the kidney?
Most K+ resides WITHIN the cell
What is the normal pH range of urine?
5.0 - 7.0
What is the purpose of tight junctions being relatively leaky?
Allows for some reabsorption to occur passively down osmotic gradient through tight junction and for “back-leak” of substances back into the lumen
Why is there more Na+-K+-ATPase pump activity in the basolateral membrane of the proximal tubule than in most other nephron segments?
Na+ levels in these cells are kept low
The following substances are coupled with sodium for transport from the luminal membrane into the proximal tubular cell. Are they co-transporters or countertransporters?
Glucose
Amino acids
Posphate, lactate, or citrate
Hydrogen ions
Glucose: cotransporters
Amino acids: cotransporters
Phosphate, lactate, or citrate: cotransporters
Hydrogen ions: countertransporters
What is isoosmotic reabsorption?
Water and sodium reabsorption occur to the same degree in the proximal tubule. Osmolarity remains relatively constant throughout the proximal tubule
What is the driving force for water reabsorption in the proximal tubule?
Transtubular osmotic gradient; established by solute reabsorption
*water follows solute*
Why is the proximal tubule highly permeable to water?
Expression of aquaporin-1 water channels allows water to move down its concentration gradient; tight junctions are also permeable to water
What are the two mechanisms for movement of fluid into peritubular capillaries?
- Net diffusion
- Bulk flow of ISF
Net filtration pressure across the peritubular capillaries always favors net movement into or out of capillaries?
Into the capillaries
What pressure is the major driving force for fluid reabsorption into the proximal tubule? What force is responsible for this movement?
Oncotic peritubular-capillary pressure (Πptc)
Starling Forces
*When Πptc is always higher than Pptc
How is bicarbonate reabsorbed? (5 steps)
- H+ is secreted (in exchange for Na+)
- Reacts with HCO3- in filtrate to form carbonic acid (H2CO3)
- Carbonic anhydrase dehydrates H2CO3 into CO2 and H2O, which can then diffuse through the luminal membrane
- Intracellular H2CO3 dissociates back into HCO3- and H+
- HCO3- exits the cell across the basolateral membrane through a facilitated diffusion transporter
What would happen to reabsorption if a person were to take a carbonic anhydrase inhibitor? (4)
- No HCO3- reabsorption
- Decreased blood pH
- Decreased Na+ reabsorption
- Decreased H2O reabsorption
Ex: acetezolamide (diuretic)
Does chloride reabsorption in the proximal tubule occur by a passive or active mechanism? Paracellular or transcellular?
Passive
Paracellular
As the proximal tubule reabsorbs filtered glucose, amino acids, and bicarbonate (all coupled with sodium), does chloride ion concentration increase or decrease within the tubule?
Increases
What transmembrane protein is permeable to chloride?
Tight junctions; allows Cl- to move down its concentration gradient; to maintain electroneutrality, Na+ follows movement of Cl-
Describe how Cl- reabsorption is linked to formate in the late proximal tubule. (4)
- H+-Na+ exchanger secretes H+ into lumen, which reacts with formate (F-) to form formic acid (HF)
- HF is uncharged, so it diffuses into the cell, where it immediately dissociates into H+ and F-
- Cl- is reabsorbed into the cell as F- is secreted back into the lumen (countertransporter)
- Cl- is cotransported with K+ out of the cell and into the peritubular capillary.
Filtration Fraction =?
FF = GFR/RBF
What happens to the RBF, GFR, and FF during constriction of the afferent arteriole?
RBF: decreases
GFR: decreases
FF: No change
What happens to RBF, GFR, and FF during constriction of the efferent arterioles?
RBF: Decrease
GFR: Increase
FF: Increase
What happens to RBF, GFR, and FF when there is an increase in plasma protein concentration?
RBF: No change
GFR: decreases
FF: decreases
What happens to RBF, GFR, and FF when there is a decrease in plasma protein concentration?
RBF: No change
GFR: Increases
FF: Increases
What happens to RBF, GFR, and FF during constriction of the ureter?
RBF: No change
GFR: Decreases
FF: Decreases
The descending limb of Henle’s Loop does not reabsorb _____, but is highly permeable to and reabsorbs ______.
Sodium
Water
The ascending limb of Henle’s Loop reabsorbs ______ and ______, but is impermeable to ______,
Sodium and chloride
Water
What is the major transporter in the ascending limb of Henle’s Loop for reabsorption of ions?
Na+-K+-2Cl- cotransporter
Why is Henle’s loop called the “diluting segment” of the nephron? The fluid that enters the distal convoluted tubule is _______ compared to plasma
Because of the reabsorption of sodium and water
Fluid in distal tubule: hypoosmotic compared to plasma
How much filtered water and sodium does Henle’s loop reabsorb?
Sodium: 25%
Water: 15%
The distal convoluted tubule and collecting duct reabsorb approximately ___% of the filtered NaCl.
10%
What ions are secreted by the distal convoluted tubule? (2)
K+ and H+
Does water become more hypoosmotic or hyperosmotic as it travels through the distal convoluted tubule?
Hypoosmotic
What hormone influences the permeability of the collecting ducts? Does the presence of this hormone increase or decrease permeability?
Vasopressin or antidiuretic hormone (ADH)
Increases permeability (though aquaporin-2 channels)
What is the purpose of the countercurrent multiplier system?
Produce concentrated urine in the Henle’s loop.
What are the steps of the countercurrent multiplier system? (3+)
- NaClK is reabsorbed from thick ascending LoH
- Hypertonic interstitium stimulates reabsorption of water from thin descending LoH
- Flow occurs within the loop so that more isotonic fluid enters the loop from the proximal tubule, and hyperosmotic fluid generated moves to ascending limb
Steps 1-3 are repeated multiple times
What is the blood vessel that directly interacts with Henle’s Loop? What function does it serve in the concentration of urine?
Vasa recta
Preserves the hyperosmotic interstitium of the osmotic gradient due to the very high medullary interstitial osmolarity
What is the rate-limiting step in the countercurrent multiplier system?
Na-K-2Cl co-transporter in the thick ascending LoH
What would be the effect(s) of inhibiting the Na-K-2Cl cotransporter with a drug like Furosemide?
Less NaCl and K is reabsorbed from thick ascending LoH
Medullary interstitium becomes less hyperosmotic and less water is reabsorbed in thin descending limb
In collecting ducts/tubules, less water will be reabsorbed because medullary interstitium is not as hyperosmotic
Describe the role of interstitial urea.
Creates hyperosmolarity in tubular fluid
Not reabsorbed in distal tubule (until it reaches the inner medulla); the high urea concentration in the inner medullary collecting duct drives reabsorption in this section (influenced by ADH)
What is the overall major function of the early proximal tubule? (1)
Isosmotic reabsorption of sodium, glucose, amino acids, phosphate, lactate, citrate, bicarbonate, and water
What is the overall major function of the late proximal tubule? (1)
Isosmotic reabsorption of Na+ and Cl- (driven by a Cl- gradient) and water
What is the overall major function of the thick ascending LoH? (3)
Reabsorption of NaCl without water
Dilution of tubular fluid
Reabsorption of Ca2+ and Mg2+ (driven by lumen-positive potential)
What is the overall major function of the early distal tubule? (2)
Reabsorption of NaCl without water
Dilution of tubular fluid
What are the three cell types of the late distal tubule and collecting ducts?
Principal cells
α-intercalated cells
β-intercalated cells
What is the function of principal cells in the collecting ducts?
Reabsorb sodium through Na+ channels
Secrete K+
What is the function of α-intercalated cells in the collecting ducts?
Secrete H+ via H+-ATPase as well as H+-K+-ATPase counter-transporter
What is the function of β-intercalated cells in the collecting ducts?
Secrete HCO3-
Reabsorb H+ and Cl-
