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

List:

· Renal handling

· Consequences of glycosuria

Renal handling:

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

Consequences of glycosuria:

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

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

List:

Renal handling:

Consequences of glycosuria:

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