Renal 2 Flashcards
reabsorption of Na
-most important function of kidney
-main determinant of ECF volume, blood volume, and BP
-water follows Na
-high Na intake -> water follows into blood -> ECF increases -> high BP + edema
-low salt -> water moves out of ECF -> volume contraction -> low BP
-kidneys must ensure Na excretion = Na intake -> Na balance
parts of nephron is relation to Na
-proximal tubule- majority of Na reabsorbed (67%) -> water follows -> isosmotic!
-thin descending limb- impermeable to Na but permeable to water -> water reabsorbed
-thick ascending limb- reabsorbs 25% Na -> diluting segment bc its impermeable to water
-early distal convoluted tubule- reabsorbs 5% -> impermeable to water
-late distal convoluted tubule - final 3%- fine tuning
-excretion of <1% Na of what is filtered
-excretion = intake of Na
-late distal tubule and collecting duct- sites of action of Na -> regulating aldosterone
proximal convoluted tubule
-entire proximal tubule reabsorbs 67% of filtered Na
-entire proximal tubule reabsorbs 67% of water
-isosmotic reabsorption- coupling of Na and water
-bulk reabsorption of Na and water important for ECF volume
-proximal tubule is site of glomerulotubular balance -> mechanism for coupling reabsorption to GFR
early/late proximal tubule
-other nutrient and ions reabsorbed right away -> highest priority
-glucose, amino acids, HCO3-
-Na reabsorbed with them down gradient created on peritubular capillary side via Na K pump
-after all these substances have been reabsorbed -> Cl concentration is high by the time it gets to late proximal tubule
-Cl is reabsorbed down its gradient in the later proximal tubule via counter transport with formate and paracellularly (between the cells)
-water and Na is also reabsorbed in late proximal tubule
isosmotic reabsorption
-hallmark of proximal tubule
-water and NaCl equally reabsorbed -> concentration of Na stays the same across entire proximal tubule bc relative to water its proportionally the same
-Na osmolarity doesnt change
peritubular capillary and reabsorption of water
-high oncotic pressure due to high protein from glomerular capillary sucks the water in and therefore Na in
-high oncotic pressure bc no proteins in in the interstitial fluid and nephron
glomerulotubular balance
-constant fraction of filtered load is reabsorbed by proximal tubule despite if filtered load increase or decrease
-increase in filtration/GFR -> if we increase solutes in filtered -> increase oncotic pressure in peritubular capillary -> decrease hydrostatic pressure in peritubular capillary -> reabsorption increases
-just bc you increase load doesnt mean you excrete more…. you reabsorb more!***
volume expansion in relation to glomerulotubular balance
-increase in ECF -> proteins are diluted -> oncontic pressure in peritubular capillary decreases -> increased hydrostatic pressure/BP
-this creates a lower driving force for reabsorption
-this increases excretion -> more urine -> this is a mechanism to decrease ECF
volume contraction in relation to glomerulotubular balance
-decrease in ECF volume (dehydration, diarrhea)
-oncotic pressure is high bc there is a lot of proteins compared to fluid in blood
-hydrostatic pressure is low
-increase reabsorption driving force
-this also actives renin-angiotensin-aldosterone system (RAAS) -> angiotensin 2 stimulates Na-H+ exchanger
-this stimulates reabsorption of HCO3-, Na, and water -> alkalosis due to excess reabsorption of HCO3-
osmotic diuretics
-increase the filtration of osmotically active substance
-increase Na and water excretion due to poor reabsorption
-increase urine
-diabetes mellitus- osmotic diuresis causes ECF volume contraction
loop on henle
-thin descending limb
-thin ascending limb
-thick ascending limb
-responsible for countercurrent multiplication - essential for concentration and dilution of urine
thin descending and ascending limb of loop of henle
-thin descending and ascending are highly permeable to NaCl
-thin descending - water moves out and solutes moving into thin descending limb -> becomes hyperosmotic
-thin ascending - impermeable to water -> solute moves out without water -> becomes hypoosmotic
thick ascending limb
-diluting segment- impermeable to water -> dilutes urine
-ACTIVE reabsorption of Na
-load dependent
-increase Na entering limb -> increase reabsorption
-reabsorbs 25% of filtered Na
-Na, K, 2Cl cotransporter - reabsorbs Na, K, 2Cl in one pump
-Na moves down gradient created by Na K pump
-Cl passively diffuses into blood
-K passively diffuses into blood or goes back into lumen (nephron)
-this cotransporter creates lumen positive potential difference (in nephron) -> allows for reabsorption of cations like Ca and Mg as well
diuretics in proximal tubule
-diuretics inhibit proximal Na reabsorption -> but some extra Na is delivered to loop of henle and reabsorbed by load dependent mechanism
-offsets proximal diuretic effect
-diuretics of proximal tublue -> mild diuresis
loop diuretics
-furosemide
-blocks the Na, K, Cl cotransporter (Cl)
-Na stays in lumen with water -> increase excretion
-blocks the reabsorption of Na and water in the loop
-can drop Mg and K - beware
terminal nephron
-distal tubule and collecting duct
-load dependent
-reabsorb less (8%)
-early distal tubule- Na-Cl contransporter
-late distal tubule and collecting duct- principal cells and alpha-intercalated cells
early distal tubule
-impermeable to water- cortical diluting segment
-Na-Cl contransporter
-Na moves down concentration gradient created by Na-K pump
thiazide diuretic
-blocks Na-Cl costransporter in the early distal tubule
-transporter transports 2 (not 3), electroneutral (not electrogenic), inhibited by thiazide diuretics
-thiazide anion binds to Cl site -> inhibits reabsorption
later distal tubule and collecting duct
-principal cells and alpha-intercalated cells
-principal cells- Na reabsorption, K secretion, water reabsorption
-alpha-intercalated cells- K reabsorption and H secretion
-reabsorb 3% of Na
-fine adjustment- hormonally regulated
principal cells
-aldosterone acts directly on cells
-increases Na reabsorption
-diffuses into cells -> nucleus -> tells it to produce more Na transport proteins -> increase reabsorption of Na
-secrete K
-K-sparing diuretics (spironolactone) - block aldosterone into nucleus -> decrease Na reabsorption (not much bc little is done here) but mainly blocks K secretion
-ADH- increases permeability of water
decrease Na intake
-decrease ECF and BP:
-sympathetic nervous system activated by baroreceptors if we reduce BP -> constrict afferent arterioles -> reduce GFR -> increase proximal tubule Na reabsorption bc vasoconstriction reduces hydrostatic pressure in peritubular capillary
-decrease ANP -> dilation of efferent arterioles -> decrease GFR -> increase Na reabsorption (in collecting ducts) -> decrease Na excretion
-increase oncotic -> increase Na reabsorption (in proximal tubule) -> decrease Na excretion
-increase renin-angiotensin aldosterone -> increase Na reabsorption (proximal tubule and collecting ducts) -> decrease Na excretion
potassium balance
-essential for normal function of excitable tissues (nerves, skeletal, cardiac)
-affects resting membrane potential
-contained within the cells
-internal K balance- regulation of K within cell
-external K balance- regulation of K in ECF by kidneys
-urinary excretion of K must be equal to K intake
-hyperkalemia- shift of K out of cells
-hypokalemia- shift of K into cells
influences of K influx and eflux
-ECF -> ICF
-increase influx of K into cell - insulin, beta 2 agonists
-after you eat -> spike in K in ECF -> insulin shuttles K into cells
-beta 2 agonist - increases K influx
-alpha agonist and exercise- increase K moving out of cell
acid-base influence of K
-acidosis- increase K leaving cell
-during acidosis H+ is high outside cell -> H+ moves down gradient into cell and K is moved out using the cotransporter -> hyperkalemia
-alkalosis - increase K entering cell
-reduced H+ outside cell -> H+ leaves cell and K moves into cell using cotransporter -> hypokalemia
-DOES NOT always produce K shift -> exceptions: respiratory acidosis/alkalosis, and excess organic acids -> this is bc it alters pH via CO2/organic anions which is not using the cotransporter
no ADH
-increase fluid loss
adrenergic agonist and antagonist of K
-catecholamines
-beta agonist > activation beta-adrenergic receptors -> shift K into cells -> hypokalemia
-alpha agonist -> activation of alpha-adrenergic receptors -> shift K out of cells -> hyperkalemia
-vice versa for antagonists
osmolarity of K
-hyperosmolarity (increase osmolarity of ECF) -> shift of K out of cells (with water)
cell lysis
-breakdown of cell membranes
-releases K out of cells -> hyperkalemia
-ex. burn, rhabdomyolysis, cells being destroyed from chemo
exercise
-K shifts out of cells
-ATP depletion -> opens K channels -> K flows out down its gradient
-usually slight but if someone is on a beta antagonist or has impaired renal function -> hyperkalemia
renal balance of K
-renal function varies with dietary K intake
-easily filtrated
-reabsorbed in the proximal tubule (67%)
-thick ascending limb reabsorbs (20%)
-*distal tubule and collecting ducts- are the main factor that secrete and reabsorb based on K diet
-low-K diet -> α-intercalated cells reabsorb K -> low urinary excretion
-normal or high-K diet -> principal cells secrete K
-urinary K excretion can be as high as 110%
factors that alter K secretion- most important factor
-the magnitude of K + secretion is determined by the size of the electrochemical gradient for K + across the luminal membrane
-this is affected by aldosterone, acid-base disturbances, dietary K + , diuretics
-increases the magnitude of electrochemical gradient for K + across luminal membrane -> increase K + secretion (vice versa)
aldosterone effect on K
-Aldosterone increases K secretion via principal cells
-increases K channels in luminal membrane -> increased driving force to increase K + secretion
-aldosterone promotes Na reabsorption so overall it increase Na reabsorption and K secretion in principal cells
loop diuretics effect on K
-Loop and thiazide diuretics -> inhibit Na + reabsorption via pumps -> Na is excreted
-loop diuretics (not thiazide) blocks K pumps along with Na -> secretion -> excreted
-diuretics also increase flow rate in the late distal tubule and collecting ducts -> dilutes the fluid -> creates gradient -> causes further secretion of K
-kaliuresis and hypokalemia
K sparing diuretics
-spironolactone, amiloride, triamterene
-do not cause kaliuresis
-inhibit aldosterone and there inhibit K secretion
-these are usually used to offset hypokalemia and kaliuresis produced by loop or thiazide diuretics
phosphate
-has role in bone and urinary buffering for H+
-soaks of H+ in urine
-85% in bone, 15% in ICF, <0.5% in ECF
-90% of phosphate if filtered…of that:
-70% reabsorbed in proximal convoluted tubule
-15% reabsorbed before loop of henle
-last 15% is excreted to uphold pH of urine
parathyroid hormone (PTH) and phosphate
-regulates reabsorption of phosphate in proximal tubule
-inhibits transporter -> decreases saturation max for phosphate reabsorption
-causes phosphaturia -> increases phosphate excretion
calcium
-handled almost the same as Na
-99% in bone, 1% in ECF and ICF
-60% filtered
-in thick ascending limb Ca is reabsorbed via paracellular route (between cells) due to + charge in lumen created by Na-K-Cl pump
-tightly coupled to Na reabsorption
-if we inhibit Na-K-Cl pump with loop diuretic -> it also inhibits Ca reabsorption -> treatment for hypercalcemia
-distal tubule- 8% Ca reabsorbed independent of Na -> this is where Ca reabsorption is regulated
-PTH increase Ca reabsorption in distal tubule -> hypocalciuric action
PTH overall
-increases Ca (hypocalciuric) in distal tubule
-increase phosphate (phosphaturic) in proximal tubule
thiazide diuretics and Ca
-increase Ca reabsorption but it decreases reabsorption for all other solutes :0
-treats idiopathic hypercalciruria
-distal tubule
-decreases likelihood of Ca stone formation
Mg
-80% is filtrable
-95% reabsorbed and 5% excreted
-30% reabsorbed in proximal tubule (small amount in comparison)
-majority reabsorption in the thick ascending limb - 60%
-thick ascending limb- reabsorbed via paracellular route (between cells) due to + charge in lumen created by Na-K-Cl pump (same as Ca)
-loop diuretic- inhibit Na-K-Cl pump -> increase Mg reabsorption -> increase Mg excretion -> hypomagnesemia
-5% reabsorbed in distal tubule
water balance-
-body fluid osmolarity- 290 mOsm/L -> via osmoregulation
-done at the late distal tubule and collecting duct -> impermeable to water in absence of ADH (vice versa)
-regulate water via ADH
lack of water
-increases plasma osmolarity
-hypothalamus senses this
-increase ADH from posterior pituitary
-ADH increase permeability to water in principle cells (late distal tubule and collecting duct)
-increase water reabsorption
-increase urine osmolarity
-decrease plasma osmolarity towards normal
drinking water
-decrease plasma osmolarity
-reduce ADH in posterior pituitary
-decrease water permeability in principle cells (late distal tubule and collecting duct)
-decrease water reabsorption
-decrease urine osmolarity
-increase urine volume
-increase plasma osmolarity towards normal
ADH effects
-1. increase water permeability of principal cells in distal tubule and collecting ducts
-2. promotes Na-K-Cl pump of thick ascending limb
-3. increases urea permeability in inner medullary collecting ducts
vasa recta
-helps to not destroy concentration gradient via countercurrent exchange (passive)
-very slow flowing blood
-solutes and water flow freely within vasa recta -> blood is so slow moving things are able to equilibrate osmolarity from when it enters to when it leaves vasa recta (300)
SIADH
-abnormally high ADH (head injury, tumors)
-increases water reabsorption by late distal tubule and collecting ducts
-urine is hyperosmotic and plasma osmolarity is diluted
central diabetes insipidus
-can follow head injury
-disables ability to make ADH
-everything is impermeable to water
-diluted urine is excreted
-high plasma osmolarity
-tx- ADH analogue (dDAVP)
