KEY wk 9, lec 3 Flashcards
division of water in body
2/3 intracellular
1/3 extracellular (20% blood plasma. 80% interstitial fluid)
fluid and salt go into ECF easily not ICF
–> water expands both
–> saline expands ECF
–> salt expands ECF and shrinks ICF
nephron reabsorb vs excrete
eabsorb essential substances such as water, glucose, amino acids, and ions while secreting waste products like urea, creatinine, and excess ions into the tubular lumen for excretion in urine.
passive diffusion
move down [ ] gradient without energy
lipid soluble substances (i.e. urea), gases, small ions, water
facilitated diffusion
carrier proteins or channels move molecules down concentration gradient without energy
i.e. glucose and amino acids
active transport
move against [ ] gradient via ATP
Na+/K+ ATPase pump (sodium out, k in)
secondary active transport (symport and anti port)
active transport; coupled movements of 2+ molecules
symport: same direction (sodium glucose cotransporter SGLT) (Na-3HCO3 symporter for bicarbonate)
anti port: opposite (sodium calcium exchanger, sodium in, ca out) (Na-H anti porter)
endocytosis vs exocytosis
Endo: engulf extracellular substance via invagination of cell membrane = form vesicle
exocytosis: reverse; vesicles with substance fuse with membrane and release content into extraceullar space
extraceullar vs intracellular ions in both
extracellular:
lots: Na+, Cl-
some: Ca2+, HCO3-, protein
intracellular
lots: K+, PO4 and organic anions
fair bit: Mg2+, protein
~100 of Na+, Cl- in extracellular
~30 of HCO3- in extracellular
~100 K+ in intracellular
water gain and loss
insensible= not aware of (NOT sweat)
input: food, drink, metabolism
output: insensible via skin and lung, sweat, feces, urine
2 routes for transporting substances in renal tubules
transcellular: apical transporter –> cytoplasm –> basolateral surface –> peri-tubular capillaries
paracellular: across tight junctions, in ECF space between cells
what cells are in the collecting tubules
principal and intercalated cells
parts of the tubule and their function
PCT- reabsorb nutrients ans 60% of water and most solutes
loop of henle thin limb: passive reabsorb water (descending) and NaCl (ascending)
loop of henle thick tiling: ionic gradient for countercurrent multiplication; dilutes urine, makes interstitial hypertonic
DCT: Na+, Cl-, water balance
collecting tubules: principal cells for absorption of Na+, K+, water and intercalated cells for acid.base and K+ homeostasis
main thing for osmolality in ECF
NaCl
ICF has how much water
2/3 of body osmotic content and therefore water
(1/3 in ECF)
but ECF and ICF is osmotic equilibrium bc water crosses cell membranes easily
water transport in tubules
move from what osmolality
always reabsorbed; never secreted
moves from low to high osmolality
na, cl and water
water and salt are freely filterable at renal corpuscle ‘
cl is passive and because of electroneutrality (- and +) its tied to Na trasnport
where does majority of Na, Cl and water get reabsorbed? how much?
2/3 in proximal tubule
where does sodium get reabsorbed
what goes to urine
65% in proximal tubule
25% un thin ascending limb and thick ascending limb of henle
little bit in DCT and collecting duct ~10%
NONE in descending thin limb of henle loop
urine= <1% of total filtered sodium
all nephron segments have what for active transceullar sodium reasbosption? keeps sodium [ ] in intracellular space ____, despite the negative charge inside the lumen (that’s why need ATP for Na+ to go against electrochemical gradient)?
Na-K-ATPase pump
low
what anions balance out sodium (cation)
mainly chloride, some bicarbonate
main reabsorption of chloride
proximal tubule
Cl- gets transported where
intracellular (even through negative inside)
–> need energy to move against gradient
how to excrete water in excess of salt and vice versa
seperate reabsorption
-the same in proximal tubule, but differs beyond
-water reabsorbed in descending henle
-Na reabsorbed in ascending henle
sodium reabsorbed in loop of henle is always ____ than water
greater
main water reabsorption via
aquaporins in plasma membranes of the tubular cells, and in the proximal tubule through the tight junctions between the cells.
i.e. proximal tubule and descending thin limb of henle highly permeable
i.e. ascending limb of henle is somewhat impermeable bc of tight junctions
i.e collecting duct in variable
Na+/K+ pumps Na+ into interstitum (basolateral side) which causes
water to follow (Pull/ solvent drag)
sodium reabsorption across apical membrane via
across basolateral
H+ and Cl-
Na+/K+ pump
SLIDE 29 DIAGRAM
PCT reabsorbs what %? and via what?
60-70% most solutes
80% bicarbonate
100% amino acids and glucose
transcelular (i.e. sodium) and paracellular
(water and anions follow sodium)
how does PCT reabsorb bicarbonate, sodium and water
Uses carbonic anhydrase and carbon dioxide production to reabsorb bicarbonate, sodium, and water
sodium glucose co transport in PCT
sodium- glucose co-transporter 2 (SGLT2) or sodium-glucose co-transporter 1 (SGLT1).n –> both go into PCT
glucose then exits via facilitated diffusion via GLUT1 or GLUT2 and go into bloodstream
amino acid transport in PCT
via secondary active transport mechanisms involving sodium co-transporters
after in cell, then can go into bloodstream by transporter proteins
phosphate reabsorption in PCT
via sodium-dependent phosphate co-transporters.
uses NaK ATPase pumps to get phosphate to go against concerntraion gradient
bicarbonate reabsorption in PCT
into PCT exchange HCO3 for Cl- via sodium-bicarbonate co-transporter (NBC)
helps with acid base balance
water reabsorption in PCT
passive, osmosis
driven by reabsorption of glucose and sodium
sodium reabsorption in PCT
active,
sodium-glucose co-transporters, sodium-phosphate co-transporters, and sodium-bicarbonate co-transporters.
once in the cell go to basolateral NAK ATPase to
potassium and chloride reabsorption in PCT
paracellular (between cells) along with water via passive diffusion driven by electrochemical gradients
method 1 of sodium reabsorption in PCT
Na/K+ ATPase pump on basolateral side
Na+ enters cell then other channels on apical membrane
water and chloride follow
method 2 of sodium reabsorption in PCT
HCO3 combines with H+
–> converted to carbon dioxide by carbonic anhydrase
CO2 diffuse into cell and then gets converted back into HCO3 and H+
▪ H+ exchanged with Na+ at the apex
▪ HCO3- co- transported across the basolateral membrane with sodium
–> can be increased by ATII
2 drivers of sodium reabsotpuon in PCT
Na/K ATPase
HCO3 and H (into CO2)
early vs pars recta (latter) part of PCT absorption
early: everything (i..e HCO3, glucose, inulin, amino acids, Na+, Cl-, H2O)
latter: Na+, Cl-, H2O
organic solutes reabsorbed in? rely on?
PCT
i.e. glucose, amino acids
via sodium gradient or negative membrane potention
what gets degraded in PCT
Many proteins (i.e. albumin and peptide/protein hormones such as insulin, GH) are degraded in the PCT and a.a.’s re-used
▪ Taken up via a process of continuous endocytosis (pinocytosis)
for apical and basal membrane which transporter for glucose
when is it saturated
Glucose is taken up across the apical membrane by sodium-glucose symporters (SGLT family) and leaves across the basolateral membrane via glucose uniporters (GLUT family)
–> main SGLT2 for glucose reabsorption (1:1 of glucose and Na+)
–> late proximal tubule is SGLT1 (2:1)
pathologic hyperglycemia
organic solutes in PCT
organic cation or organic anion transporters (OCT or OAT, respectively) and are found on the basolateral membrane
cations: histamine, serotonine, Ach, NE…
anions: bile salts,fatty acids…
organic cation transporters and organic anion transporters in PCT
OCTs use inside-negative membrane potential to move cations from the bloodstream into the PCT cell
OATs use countertransport – the anion is transported from bloodstream into PCT cell, and alpha-ketoglutarate is exchanged in the opposite direction
what do organic anion transporters use to get the negative charge into cell
alpha ketoglutarate
principal cells regulate water and sodium transport in DCT via influence of which homrone
aldosterone
DCT; principal cells and aldosterone secretion for
- Sodium Reabsorption * Water Reabsorption
- Potassium Secretion
sodium reabsorption via principal cells
epithelial sodium channels (ENaC) in apical membranes
regulated by aldosterone which binds mineralocorticoid receptors in cytoplasm of principal cells which upregulates ENaC
aldosterone increases sodium reabsoprtion
water reabsorption by principal cels
sodium reabsorption (via aldosterone) creates osmotic gradient for water reabsorption
- Aquaporin-2 (AQP2) water channels on apical membrane
potassium secretion via principal cells
aldosterone stimulates Na/K ATPase on basolateral side to pump sodium out and K+ in
increase intracellular potassium causes secretion through tubular lumen on potassium channels on apical membrane
DCT principal cell action
Na and H2O reabsorb (via aldosterone)
K+ secrete
~~electrolyte balance
dilute vs concentrated unirine via which part of nephron
nephron’s loop of Henle, which utilizes countercurrent exchange and multiplication mechanisms.
countercurrent exhanger and multiplier in loop of henle to concentrate or dilute urine
descending: water
ascending: Na, Cl, potassium (impermeable to water)
countercurrent exchanger: water diffuse out of tubule into interstitum in descending limb increasing the osmolarity of medulla interstitium. in ascending limb Na and Cl are transported out into intersititumn, create concentration gradient in mdeulla
multiplier effect: amplify [ ] gradient in medulla; via sodium- potassium-chloride cotransporter (NKCC) channels in ascending limb. high osmolarity in renal medulla= water reasborb in collecting duct
hypothalamic regulation of urine concentraion
hypothalamus monitors blood osmolarity and regulates ADH secretion from posterior pituitary
hypothalamus when osmolarity increases (dehydrates) causes _____ secretion
ADH secretion (promotes water reabsorption in collecting ducts)
ADH impacts on urine
increases permeability of collecting ducts to water via aquapoirn 2 channel addition in apical membrane
allows for passive reabsoprtion of water = more concentrated urine
urea trasnporters have what impact on urine
in thin ascending limb
UT-A1 and UT-A3; concentrate urine
NKCC channels impact on urine
concentrates urine
aquaporins impact on urine concentraion
aquaporin2 on apical membrane
water reabsoprtion ; concentrate urine
via ADH; water out of tubule into interstitium
hairpin loop structure of loop of henle and vasa recta for urine concentraion
henle hairpin loop to maximize countercurrent exhange and multipliers
allows for the close proximity of the descending and ascending limbs, facilitating the exchange of ions and water between these segments.
vasas rectae (peritubular capillaries running parallel to henle); when blood flows it exhanges ions and water in interstitium. concentrates medullary envo
RAAS system for regulation of
controlled by
ultimately for which homrone
renal sodium excretion
sympathetic neural signal via vascular baroreceptors
alodterone (sodium and water retention, K excretion)
RAAS system:::
where is angiotensinogen made
how to turn angiotensinogen to ATI
enzyme to make ATI to ATII
renin is made by? which cells?
liver
need renin to turn angiotensinogen into ATI
ACE
juxtaglomerular apparatus (renin secreting cells in late afferent arteriole before glomerulus); granular/ JG cells
3 regulators that control renin secretion by JG/ granular cells
Sympathetic Input via the renal sympathetic nerve
Pressure in the afferent arteriole
Macula densa release
renin has inverse relationship with
dietary sodium
A high sodium diet suppresses renin secretion
A low sodium diet leads to high levels of renin.
sympathetic input affecting renin secretion
NE –> beta1 adrenergic receptors on JG cells–> activate cAMP–>release renin
vasculature: high pressure suppresses renin, low vascular volumes via baroceptosr increase renin
afferent arteriolar pressure impact on JG/granular cells and renin
decrease pressure, increases renin
unless major recall arterial blockage
act as baroreceptors
drop in pressure= secrete renin to increase pressure
impact on macula densa to control renin production
high Na: release adenosine/ ATP
low Na: release NO and prostaglandins
—-
macula densa respons to high tubular sodoium –> adenosine/ ATP binds purinergic receptors on JG/granular cells –> increase Ca+ and reduce renin and decrease GFR
reduce renin and excrete more (have too much)
if have low tubular sodium macula densa will release nitric oxide and prostaglandin’s –> cAMP –> renin production, increase GFR
angiotensinII to preserve blood volume and blood pressure via
Vasoconstriction
Stimulation of sodium tubular reabsorption
Stimulation of the CNS: Salt appetite, thirst, and sympathetic drive Stimulation of aldosterone secretion
vasoconstriction via AT2
reduce renal blood flow, reduce GFR, decrease filtered load of sodium
ATII stimulates what in the proximal and distal tubule to cause Na+ reabsorption
proximal: NHE3 (Na+/H+ antiporter on antiporter) and Na/K+ ATPase
distal: NCC (Na+/Cl- symporters and sodium channels (ENaC)
In the proximal tubule it stimulates the NHE3 sodium/hydrogen antiporter in the apical membrane and the Na-K-ATPase in the basolateral membrane.
In the distal tubule and connecting tubule it stimulates the activity of NCC sodium/chloride symporters and sodium channels (ENaC) that import sodium.
how to help with blood pressure and volume
aldosterone stimulate sodium retention
reabsorb in distal tubule
aldosterone crossing cell membrane
aldosterone has enough lipid character to freely cross tubular cell membranes
–> combines with mineralocorticoid receptors in the cytoplasm
–> binding promotes nucleus transcription factors….
increase activity of sodium channels (ENaCs) and basolateral membrane Na-K-ATPase pumps.
and luminal NCC sodium/chloride symporters when ATII elevated
majority of calcium reabsorbed in
PCT
paracellular (tight junctions)
transceellular (calcium channels on luminal side, transporter on basolateral
phosphate reabsorption in PCT
via sodium-dependent phosphate co-transporters
calcium and phosphate in Thick Ascending Limb of the Loop of Henle
Ca2+ is minimal and paracellular
no phosphate reabsorption
calcium and phosphate in Distal Convoluted Tubule (DCT) and Connecting Tubule (CNT):
Ca2+ finetuning via parathyroid hormone (incerate # of calcium channels)
–> also in collecting duct via PTH and calcitonin (minimal)
minimal phospahte reabsorb ; mostly secretion
phosphate excretion in urine via
parathyroid hormone and fibroblast growth factor 23 (FGF23).
buffer system in body to maintain pH balance by miming changes in H+ ions
Carbonic Acid-Bicarbonate Buffer System Protein Buffer System
Phosphate Buffer System
Ammonia Buffer System
Bone Buffer System
carbonic acid-bicarbonate buffer system
location
in ECF, including blood plasma
carbonic acid (H2CO3) and bicarbonate ions (HCO3-) t
protein buffer system
which proteins and where
hemoglobin in red blood cells and albumin in plasma, act as buffers in both intracellular and extracellular compartments.
The amino acid residues of proteins contain both acidic and basic groups that can accept or donate H+ ions
phosphate buffer system
location
ICF and renal tubular fluid
(HPO4^2- and H2PO4^-) act as weak acids and bases, respectively,
ammonia (NH3) buffer system location
location
renal tubular fluid and urine
into ammonium NH4+ in urine
bone buffer system
location; what salts
bone tissue, calcium salts (calcium carbonate and calcium phosphate)
these alkaline salts neutralized excess H+ in blood
which acid base component is highest in blood
where is it mostly in
bicarbonate
proximal tubule (doesnt change acid base balance in body
in distal/ collecting tubules it will secrete bicarbonate or proteins (H+) to alter body acid base status
where is most bicarbonate reabsorbed
PCT
2 ways to reabsorb bicatboante
- hydrogen ions and bicarbonate are generated from CO2 and water; via carbonic anhydrase
H+ secreted into lumen via Na+ antiporter or H-ATPase
- sodium-bicarbonate symporter moves bicarbonate into lumen
Na-H antiporter (NHE3)
bicarbonate that enters in symport with sodium enters via a member of the NBC family of transporters
bicarbonate and hydrogen summary for renal transport
predominant proximal tubule mechanisms for reabsoprtion of bicarbonate. hydrogen ions and bicarbonate are produced intracellularly. the bicarbonate generated within the cell is transported into the interstitium via Na-3HCO3 symporter (member of NBC family). Most of the hydrogen ions are secreted via Na-H antiporter (member of NHE family); while some are secreted via an H-ATPase. Additional bicarbonate enters the cells via an Na-HCO2 symporter (another member of the NBC family with 1:1 stoichiometry) and leaves via the Na-3HCO3 symporter. The process is ultimately powered by the Na-K-ATPase that creates the sodium gradient that drives the Na-H antiporter.
type A vs type B intercalated cells
type A: secrete H+ (H-ATPase) , reabsorb HCO3- via AE1 antiporter
–> H+ into lumen and HCO3 into blood (remove excess acid)
type B: secrete bicarbonate (pendrin antiporter)
–> into lumen to remove excess base from the blood
glomerulotubular balance
intrinsic ability of the renal tubules to adjust their reabsorption rates according to changes in the filtered load of a substance
water and solute reabsorption
bc of what force
peritubular capillaries and vasa recta
high hydrostatic pressure in peritubular causes renal tubules back to blood (reasbpsrption)
low hydrostatic pressure in vasa recta for to minimize washout of medullary concentration gradient (medullary gradient) (for urine concentration)
sources of acids and bases from diet
carb metabolism: pyruvic acid (glycolysis) and lactic acid (anaerobic)
dietary weak acids: citrus fluids when metabolized produce alkalizing substances –> co2 + h2o
fat metabolism: beta oxidation –> acetyl coa –> co2 + h2o
but if incomplete oxidation –> ketone bodies –> acidic
protein metabolism: sulfure containing amino acids make acids… also keto acid intermediates
GI secretions (i.e stomach acid, bicarbonate from pancreas)
renal disease impacting acid base
acidosis
cant excrete H+ or reabsorb bicarbonate
renal response to acidosis and alkalosis
acidosis: reabsorb HCO3 and increase H+ secretion into urine
alkalosis: decrease bicarbonate reabsorption and decrease hydrogen secretion (less bicarb in blood, retain more H+)
respiratory response to alkalosis or acidosis
acidosis: increase breathing; hyperventilate decreases CO2, reduce H+ (shift left to carbonic-acid bicarbonate buffer system)
alkalosis: decrease breathing; hypoventilation; increase CO2 (shift right in buffer system) increase H+
4 categories of acid base disorders
(1) high pCO2 is a respiratory acidosis
(2) low pCO2 is a respiratory alkalosis
(3) low bicarbonate is a metabolic acidosis (4) high bicarbonate is a metabolic alkalosis.
renal response to respiratory acidosis
i.e. COPD increased PCO2 and decrease pH so then increase bicarbonate in kidneys to help
4 categories of acid base disorders
(1) high pCO2 is a respiratory acidosis
(2) low pCO2 is a respiratory alkalosis
(3) low bicarbonate is a metabolic acidosis
(4) high bicarbonate is a metabolic alkalosis.
