Lecture 38: Renal Tubular Function Flashcards
where does tubular reabsorption occur
- across all epi cells lining the nephron
- PCT makes largest contribution
why is tubular reabsorption important
- keeps fluid loss through urine at 1-2L/day so prevents dehydration
outline the ways that molecules move from the filtrate into the blood and vice versa
- paracellular (between cells); small ions e.g. H2O driven by [Grad]
- transcellular (through cells)
- reabsorption (filtrate to blood)
- secretion (blood to filtrate)
- excretion (eliminated from the body via urine)
where are glucose transporters located within the nephron
PCT
what glucose transport proteins are located in the early PCT
- SGLT2
- GLUT2
what glucose transport proteins are located in the late PCT
- SGLT1
- GLUT1
what limits the maximum rate of glucose absorption
the rate at which the transporters can operate
when might the glucose transport maximum be exceeded resulting in glucosuria
- diabetes
- dysfunction in reabsorption (Fanconi syndrome)
- induced by drugs e.g SGLT2i
why might drugs e.g. SGLT2i be used to induce glucosuria
to remove excess urine from the blood e.g. in diabetes
what limits the transport maximum (Tm) of amino acids
speed of the pumps
are a majority of amino acids normally reabsorbed or excreted
> 95% aa normally reabsorbed
what can result in aminoaciduria
- congenital disorders of aa metabolism
- transport defects (Hartnup disease)
where in the nephron does most Na+ reabsorption take place
PCT (70%) by secondary active transport
how are most Na+ ions reabsorbed
active transport via transcellular route
what drives the reabsorption of Na+ in the PCT and LoH
Na+ gradient between filtrate and cell (maintained by basolateral membrane Na+/K+ pump)
what limits Na+ reabsorption
- majority gradient limited
- after most reabsorption occurs, limited by expression of Na+/K+ pump
how does aldosterone affect Na+ reabsorption and when might this occur
- ^ Na+ reabsorption
- by ^ expression of Na+/K+ pump
- can occur in conditions where blood osmolarity is low
describe the therapeutic potential of Na+ wasting
- reduces reabsorption of Na+ –> allows water to be excreted
- can reduce the blood volume heart has to pump
- help treat conditions e.g. hypertension and HF
outline what drugs can be used to achieve Na+ wasting
- spironolactnone
- -> inhibits action of aldosterone on Na+/K+ pump expression
- loop diuretics
- -> inhibit Na+/Cl-/K+ transporter in asc. limb
- thiazides
- -> inhibit Na+/Cl- transporter in DCT
how is water reabsorbed
- via paracellular and transcellular routes by osmosis in response to osmotic gradient created by Na+ movement
- follows movement of Na+ ions
- Transcellular passage of water is facilitated by aquaporins
how is water predominantly reabsorbed in PCT
paracellularly
how is water predominantly reabsorbed in DCT and CDs
transcellularly under control of ADH
how does ADH encourage water reabsorption in DCT and CDs
^ permeability by promoting insertion of aquaporins
name the mechanism that facilitates H2O reabsorption in LoH
counter current multiplier
outline the process of the counter current multiplier
- LoH limbs arr. w/ flow in opposition to that of vasa rect
- Na+ actively pumped out of asc. limb and moves passively into blood
- Conc blood moves along vasa recta towards desc. limb
- promotes H2O reabsorption from desc. limb
- H2O loss from filtrate makes it conc; moves to asc. limb
- Na+ again actively pumped out of asc. limb into vasa recta creating a cycle
- blood and filtrate both became conc. then diluted again
what is the net effect of the counter current multiplier
Na+ and H2O are reabsorbed
how much urea is reabsorbed in PCT
50%
where in the nephron is urea secreted back into tubular lumen and by what process
- facilitated diffusion via urea transport proteins
- asc. loop
where does secondary reabsorption of urea take place
CDs
how much urea is actually excreted in urine
20%
why is the reabsorption of urea very important despite the fact it is a waste product
contributes to hyper-osmolarity of medullary interstitium which makes water reabsorption more effective
what is uraemia a clinical indicator of
renal failure (Px likely to have other conditions due to the lack of kidney function)
what is the normal range for urea in plasma
3.3-6.7mmol/L
what is tubular secretion
when substances are removed from blood or interstitium to the tubular fluid for excretion in kidneys
(irrespective of glomerular filtration or substance [grad])
why is tubular secretion important
- important in elimination of metabolites and toxins e.g. creatinine and uremic toxins via organic cation/anion transporters
- important in clearance of some drugs e.g. antibiotics, NSAIDs and statins
how can tubular secretion be measured and for what reason
can be measured from e.g.
- para-aminohippurate clearance (PAH; filtered and secreted
- cinnamoylglycine clearance (CMG; secreted > filtered)
- secretion rates linked to disease progression
