Tubular Function I: Sodium Transport Flashcards
Intracellular and Extracellular Space/Fluid
- Intracellular space is the space within cell membranes
- Extracellular space is the space between cells (interstitial fluid) and within blood vessels (plasma)
- Electrolyte composition (e.g. salt and water content) of interstitial fluid and plasma is identical
60:40:20 rule
•Total body water (TBW)= 60% of body weight
-60% x 60kg = 36L v
•Intracellular water (ICF) = 2/3 of total body water
-2/3 x 36L = 24 L v
•Extracellular water (ECF) = 1/3 of total body water
-1/3 x 36L = 12 L
•Extracellular Fluid
- v Plasma water = ¼ of extracellular water
- 1/4 x 12L = 3 L
- v Interstitial fluid = ¾ extracellular water 3/4 x 12L = 9 L
Osmolarity
•Osmolarity (Osm/L) = # of particles into which a substance dissociates in solution × molar concentration
– 1 mole of glucose = 1 osmole of solute
– 1 mole of NaCl = 2 osmoles of solute
•Electrochemical Equivalence: • Equivalence (Eq/L)= valence × molar concentration – For monovalent ions, 1 mole = 1 Eq (and 1 mmol = 1 mEq) – For divalent ions, 1 mole = 2 Eq (and 1 mmol = 2 mEq)
Electrolytes and Water
- Salt is not produced or consumed by the body so balance is maintained by regulating the amounts excreted in body fluids (urine, sweat, stool) such that they equal the amounts ingested (ingestion = excretion)
- Kidneys maintain water and salt balance in the body by regulating output of both in the urine
Expression of Na and Water Transporters/Channels Along Nephron
- Expression of Na transporters is specific for each segment of the nephron
- Some segments are only permeable to water, other are permeable to Na, some are permeable to both Na and water
Renal tubules have a finite capacity to reabsorb glucose
- If glucose concentrations in the blood exceed the tubular transport capacity of SGLT glucose is seen in the urine
- Urine test for diabetes – glucose stick
Apical Na+ re-absorption mechanisms vary between segments
- Proximal tubule: several Na+ co-transporters (SGLT1/2, NaPi2) and the Na+/H+ exchanger (NHE3).
- Thick ascending limb: Na+-K+-2Cl– co-transporter (NKCC2/BSC1)
- Distal convoluted tubule: Na+-Cl– co-transporter (NCC/TSC1)
- Collecting duct: Epithelial Na+ channel (ENaC)
- Sodium is kept low inside all renal epithelial cells by the action of the Na+-K+-ATPase in the basolateral membrane. Na+ is moved from tubular epithelial cells to peritubular interstitium and K+ is moved into the cells.
Renal Handling of Glucose - Proximal Tubule
- Apical SGLT2 – low affinity, high capacity Na+-glucose cotransport; driven by electrochemical gradient for Na+ (established by basolateral Na+-K+-ATPase)
- Basolateral GLUT2 – facilitated diffusion
Renal Handling of Glucose - Late Proximal Tubule
- Apical SGLT1 – high affinity, low capacity 2 Na+-glucose cotransport; driven by electrochemical gradient for Na+ (established by basolateral Na+-K+-ATPase)
- Basolateral GLUT1 – facilitated diffusion
- Filtered Load — the amount of a substance filtered each minute. For a freely filterable substance (i.e. glucose), filtered load = GFR × plasma concentration of that substance.
- Transport Maximum (TmG) — the maximum transport rate for a substance. In the case of glucose, this is the maximum reabsorptive rate. The Tm for a reabsorbed substance is reached when the (limited number of) carriers are saturated and transporting glucose at the maximal rate. Glucose excretion occurs if the filtered load of glucose exceeds the TmG for any nephron.
- Threshold — the plasma concentration of a substance above which the substance is excreted. (Or, the minimum plasma concentration of a substance that is necessary to result in excretion of the substance.)
- Splay — the rounding of the reabsorption curve. It reflects the fact that all nephrons do not have identical filtering and reabsorptive capacities.
Diabetes Mellitus
Normal PGlu = 80 mg/dl
- Glucose threshold = 200 mg/dl
- In diabetes mellitus, PGlu can easily exceed the threshold (reaching levels perhaps as high as 500 mg/dl). Assuming a normal GFR, the filtered load of glucose (GFR × PGlu) in diabetes mellitus exceeds the TmG, and glucose spills into the urine
Mutations of Na+-Glucose Cotransporters
•Familial renal glucosuria
- Mutation of SGLT2 decreases the transport capacity of this carrier –> reduces TmG –> glucosuria.
- Can lead to a reduction in plasma glucose concentration.
•Glucose-galactose malabsorption syndrome
- Autosomal recessive 1 bp mutation of SGLT1 decreases the transport capacity of this carrier –> reduces TmG –> mild glucosuria. (Recall that this carrier reabsorbs only that portion of filtered glucose that reaches the last proximal tubule.)
- Because this transporter is also found in the intestine, the mutation also causes intestinal malabsorption of glucose and leads to severe (sometimes fatal) diarrhea in neonates
Passive Reabsorption of Substances along the Nephron:
- Passive reabsorption by diffusion (urea and chloride)
- Relies on transtubular electrochemical gradients and the permeability of the tubular epithelium to the substance.
TUBULAR SECRETION Quantifying Secretion
For a substance (Z) handled by filtration and secretion (no reabsorption):
Quantity secreted / min = quantity excreted / min – quantity filtered / min
Quantity excreted / min = V × UZ
Quantity filtered / min = “filtered load“ = GFR × PZ
Quantity of substance Y secreted / min = ( V × UZ ) – ( GFR × PZ )
PAH (para-aminohippurate) Handling by the Kidney
- Para-aminohippuric acid (PAH) is a diagnostic agent used to measure renal plasma flow.
- PAH is useful as a measurement of renal plasma flow because in addition to being freely filtered it is also secreted by the renal tubules, not reabsorbed.
- The renal clearance of PAH is useful in calculation of renal plasma flow (RPF).
Additional compounds secreted by the renal tubules
