lecture 4 Flashcards
function of kidney
central regulator of homeostasis; we take in more than we need to replace that which we have ‘used up’ - kidney regulates
purpose of filtration
no pumps for excess H2O or urea; production of urine through glomerular filtration but can’t afford to lose all of water and small molecules that pass through filter
why control reabsorption and secretion
take in more salt and water than needed; reabsorb 99% ultrafiltrate; maintain solute balance, plasma concentration and pH
define osmolarity
measure of osmotic pressure exerted by solution across perfect semi-permeable membrane; all concentrations of different solutes (mmol/l) added together - each ion counted separately
what is osmolarity dependent on
number of particles in solution, not nature of particles
normal plasma osmolarity vs urine osmolarity
285-295 mosmol/l for plasma (controlled), 50-1200 mosmol/l for urine (changes massively)
effect on water movement if solute present at equal concentrations either side of semi-permeable membrane
no net effect
transcellular vs paracellular
depends on how tight junctions are
passive movement
protein independent transport (lipophilic) - linear, protein dependent transport (hydrophilic) - limited by number of protein channels available
active movement
primary: dependent on amount of ATP; secondary: dependent on amount of primary ATP
water transport
low to high osmolarity through aquaporins or tight junctions
increase rate of passive uptake system
store channel proteins in vesicles and place in membrane
protein reabsorption
endocytosis of protein and receptor; drop pH in endosome, protein dissociates from receptor which goes back to membrane
transport maxima
doesn’t apply to individual cells (whole system); can vary dependent on circumstances - at high specific solute concentrations can’t absorb any more - maximum (Tm); Tm basal and stimulated (e.g. glucose - becomes present in urine; diabetes mellitus; also vitamins B and C)
secretion opposite to reabsorption
H+, K+, choline, creatine, penicillin, other drugs secreted
non-uniform reabsorption of Na+
most in proximal tubule, then loop of Henle (generate high concentrations of urine when conserving water), then distal convoluted tubule; variable amount in collecting duct (regulated most tightly by aldosterone and ADH)
proximal convoluted tubule
dense brush border, mitochondria for Na+ reabsorption, large SA
thin descending limb of loop of Henle
fewer mitochondria, loose tight junctions (reabsorb water)
thick ascending limb of loop of Henle
lots of mitochondria for Na+ reabsorption
distal convoluted tubule
less mitochondria than thick ascending limb of loop of Henle
collecting duct
some mitochondria
proximal convoluted tubule basolateral membrane
constant Na+ exchange out of cell for K+ to maintain resting potential - requires energy (primary)
early proximal tubule
Na+ co-transported in apical membrane with glucose and amino acids (secondary), glucose and amino acids move out basolateral; Na+ entry down large electrochemical gradient can bring about uphill entry of glucose and amino acids and exit of H+
early proximal tubule
Na+ in, H+ out - binds to HCO3- and water diffuses in by osmosis (regeneration of H+ in cell); carbonic anhydrase activity leads to Na+ reabsorption and increased urinary acidity
passive reabsorption
urea, water
active reapsorption
glucose, amino acids, Na+, K+, Ca2+, vit C, uric acid
net secretion by proximal convoluted tubule
route of excretion for some substances, some drugs enter tubular gluid here and act further down nephron
descending limb of loop of Henle
loose tight junctions so water reabsorbed, draws in Na+ and K+, squamous epithelium with few mitochondria
ascending limb
cuboidal epithelium, few microvilli, many mitochondria; Cl- actively reabsorbed with Na+ passive reabsorption with it, HCO3- reabsorbed, impermeable to water as tight tight junctions; hypo-osmolar fluid leaves loop of Henle; loop diuretics block Na+/K+/Cl- cotransporter
distal convoluted tubule
proximal: cuboidal epithelium, few microvilli; complex lateral membrane with interdigitations with Na+ pumps; if block lumen membrane Na+/Cl-, more Na+ in from blood so more Ca2+ out, so more Ca2+ absorbed from lumen - increase plasma Ca2+ (thiazides drug); numerous large mitochondria; Na+ and Cl- cotransporter linked to Ca2+ reabsorption; specialisation at macula densa in glomerulus (near distal convoluted tubule) detects changes in [Na+] of filtrate
distal convoluted tubule: distal
sodium reabsorbed dependent on aldosterone
collecting duct
sodium reabsorbed dependent on aldosterone, adjustment of Na+, K+, H+, NH4+; water reabsorbed under ADH control; impermeable to water without ADH; tight junctions so very little paracellular transport
principal cell
important in Na+, K+ and water balance mediated by Na+/K+ pump
intercalated cell
important in acid-base balance (mediate via H-ATP pump)
single gene defects: renal tubular acidosis
hypercholermic metabolic acidosis, impaired growth, hypokalemia; not secreting H+; occurs distally or in early proximal; failure to reabsorb filtered HCO3- from urine; leading to urinary wastage of HCO3- and acidaemia (low blood pH)
single gene defects: Bartter syndrome
mutation in ascending loop of Henle; excessive electrolyte secretion due to mutation in Na+/Cl-/K+ transporter in apical membrane, antenatal: premature birth, polyhyramnios; severe salt loss, moderate metabolic alkalosis; hypokalemia; hyponatraemia; renin and aldosterone hypersecretion
single gene defects: Fanconi syndrome
increased excretion of uric acid, glucose, phosphate, bicarbonate; proximal tubules; increased excretion of low molecular wieght proteins
associated with renal tubular acidosis type 1 (Dent’s disease): CIC-5 mutation: drop pH in endosome as H+ out, Cl- in so increases electrochemical gradient so more H+ in separately - impaired in proximal tubule so receptor can’t dissociate as pH too low - lack of absorption as endosome required
