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

Filtration

·   Polar but small molecule 180g/mol

·   Freely filtered

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

Reabsorption

·   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

Graph

·   Transport maximum (T_M):

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 T_M

o Hence leftward shift of excretion curve

Renal

·   ↑Tubular and urinary [glucose]

·   Osmotic diuresis

·   Washout of hypertonic medullary interstitium

·   ↑Na⁺/K⁺ antiport in distal nephron

·   ↑Risk UTI

Systemic

·   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