Lecture 9: Tubular Resorption, Secretion, Clearance Flashcards
Equation for excreted amount of a substance
Amnt excreted = filtered + secreted - reabsorbed
Reabsorption general processes
- Diffusion (across tight junctions)
OR - Mediated transport (through transport proteins)
Then diffusion/bulk flow from interstitum to capillaries
Transport maximum Tm
Max. material transportable per unit time
Renal clearance
Clearance of X = mass excreted / plasma conc. = Urine [X] * urine vol. / plasma [X]
Filtered load equation
Filtered load = GFR * plasma [X]
Mechanisms of renal autoregulation
Maintains constant renal blood flow/GFR
1. Myogenic control (arterial stretch reflex)
2. Tubuloglomerular feedback
Tubuloglomerular feedback for renal autoregulation
- Macula densa secretes adenosine with increased solutes -> paracrine vasoconstrict. of aff. arteriole
- Low solutes -> PGs, NO secretion -> vasodilation + renin release stimulation
Urinary Excretion Rate
E_x = urine [X] * urine flow rate; amount of X excreted per time
Na+ transporters by tubule segment
PT: SGLTs, NHEs
Thick AL: NKCC2
Early distal: NCC (Na/Cl cotransporter)
Late distal, CDs: ENaC
General kidney Na+ reabsorption processes
Mostly transcellular
- Apical: channel diffusion, cotransport
- Basolateral: Na+/K+ ATPase pump
Basolateral Na+/K+ ATPase roles
Keeps IC Na+ low and maintains IC negative charge -> provides electrochem. driving force for Na+ import
- Enables cotransport/exchange with Na+ (SGLT, NHE, etc.)
Renal glucose transporters
Occurs in PT
1. SGLTs (apical)
2. GLUTs (basolateral)
Proximal tubule SGLTs
Apical membrane
SGLT1 = 2 Na+ w/ 1 Gluc.
SGLT2 = 1 Na+ w/ 1 Gluc.
Proximal tubule GLUTs
Basolateral membrane
GLUT1/2 are uniporters
Glucose filtration rate
Glucose filtration exactly proportional to plasma concentration; Tm»_space; normal plasma glucose
Excess load is excreted (diabetes, renal defects, SGLT2 inhibs.)
H2O reabsorption by tubule segment
PT: isoosmotic reabsorption (no ADH regulation)
Thin DL: driven by high medullary interstitum Osm
Ascend. limb: no H2O reabsorption, NKCC2 only
DT, CDs: controlled by ADH (AQP2)
What drives H2O reabsorption?
Water follows ions in PT, DL
AQPs for transcellular transport under ADH control
How does ADH control H2O reabsorption?
ADH -> CD ADH receptors -> increase in cAMP -> increase in PKA activity -> increased AQP2 membrane fusion
Proximal secretion of organic cations/anions
Endogenous waste/foreign chemicals can’t be filtered as they are often bound to proteins; secreted in PT
Organic Cation Transporters
Promiscuous transporter family that secrete organic cations in PT
Organic Anion Transporters
Basolateral organic anion secretion via αKG exchange
Apical organic ion secretion
Apical transporters e.g. MDR1, MRP2; upregulated in chemo to excrete drugs
Clearance
The constant removal of waste, ingested substances, and extra salt/H2O
Whole body clearance
Removal by all organs (urine, feces, exhalation)
Renal clearance
Volume of plasma cleared by kidneys per unit time (different from excretion rate!). Must be calculated.
How can GFR be measured based on clearance?
Inulin (exogenous) or creatinine (endogenous) are used where amount filtered = amount excreted
Inulin clearance equation for GFR
Inulin clearance = GFR = urine [inulin] * urine volume / plasma [inulin]
Ratio of excretion rate to plasma concen.
Fick Principle
Amount entering = amnt leaving
How to measure Renal Plasma Flow
Using PAH; almost all entering the kidney is filtered + secreted (OATs), giving renal plasma flow
Calculating effective RPF w/ PAH
RPF = PAH clearance = urine [PAH] * urine volume / plasma [PAH]
Calculating renal blood flow
RBF = RPF / (1 - Hcrt)
