1999A04 Explain how the kidney handles glucose. Describe the physiological
consequences of glycosuria.



·         Renal handling

·         Consequences of glycosuria


Renal handling:


·   Polar but small molecule 180g/mol

·   Freely filtered

·   Normal plasma concentration 4mM, hence 900mM/day


·   Near 100%

·   From urine into cell:

o Via sodium-glucose cotransporter-1 (SGLT1) in proximal straight tubule

o Via SGLT2 in proximal convoluted tubule

o Gradient established by basolateral Na+K+ATPase

o i.e. secondary active transport

·   From cell into interstitium:

o Via GLUT-2 (i.e. facilitated diffusion)

·   Water follows by osmosis



·   Transport maximum (TM):

o Due to limited number and capacity of SGLT2

·   Splay: due to differential reabsorptive capacity of nephrons

o Predicted threshold: 375/125/180 = 0.0167M = 16.7mM

o Actual threshold: 10mM

·   Effect of SGLT-2 inhibitor: (my thoughts only!)

o Downward shift of TM

o Hence leftward shift of excretion curve


Consequences of glycosuria:


·   ↑Tubular and urinary [glucose]

·   Osmotic diuresis

·   Washout of hypertonic medullary interstitium

·   ↑Na+/K+ antiport in distal nephron

·   ↑Risk UTI


·   Dehydration, ↑osmolality

·   ↓blood volume, ↓mAP, ↓organ perfusion, ↓pH, organ dysfunction

·   Loss of nutrient and energy

·   Loss of Na+: due to medullary washout

·   Loss of K+: due to medullary washout and ↑Na+/K+ antiport in distal nephron (aldosterone)

Compensatory responses

·   To hyperosmolality: ↑ADH

·   To hypovolaemia: ↑ADH, ↓ANP

·   To hypotension: ↑SNS, ↑RAAS, ↑ADH




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