Salt and water handling Flashcards
Water content in various tissues
Kidney heart lung skeletal muscle brain skin liver skeleton adipose tissue
Division of TBW
60% body weight
1/3 ECF (20%), 2/3 ICF (40%)
ECF: 1/4 plasma (5%), 3/4 ISF (15%)
ISF
fluid in lymphatics
crystallized water in bone
CT
transcellular fluid (intraocular, CSF, synovial, peritoneal, pleural, pericardial fluids)
Osmolarity
osmol/L water
Osmolality
osmol/kg water
ECF solutes
Na+
Cl-, HCO3-
ICF solutes
K+
proteins, organic phosphates, acids
Plasma water content
93%
Normal osmolality
280-300 mosmol/kg water
Effective osmoles
Na+
cells
plasma proteins
Ineffective osmoles
urea
Tonicity
effective osmoles /solution
Starling’s forces
Jv = Kf ((Pc - Pi) - (pic-pii)) Pc = hydrostatic pressure in capillaries Pi = hydrostatic pressure in interstitium pic = oncotic (colloid) pressure in capillaries pii = oncotic pressure in interstitium
Colloid pressure is key in maintaining intravascular volume
Physiological vasculature fluid movement
Hydrostatic - favours movement out of vasculature
Oncotic - favours retention
Net result = slight movement out of vasculature - absorbed by lymphatics and returned to venous circultaion
Causes of edema
Increased vascular permeability Increased hydrostatic pressure in vasculature Decreased oncotic pressur Lymphatic obstruction Increased oncotic pressure in ISF
Glomerulus filtering
freely filters Na+ and Cl-
PCT
65% Na+ and H2O reabsorbed
Sodium reabsorption in early PCT
Na/K ATPase on basolateral membrane: 3Na out of cell, 2K into cell
Establish a electrical gradient –> allows Na to move down the gradient into the cell
2 mechanisms of Na movement into cells:
1) Na+/H+ exchanger (NHE3):
- H+ generation by dissociation of H2CO3 (generates HCO3-)
- H+ moves into lumen, combines with HCO3- to form H2CO3, which dissociates to CO2 and H2O (carbonic anhydrase)
- CO2 diffuses into cell, gets converted to H2CO3 by carbonic anhydrase
- HCO3- moves into interstitium and is reabsorbed by blood
2) Na+/X- cotransporter
- Na+ moves down concentration gradient along with another solute
- X = amino acids, phosphate, citrate, glucose
Once in the cell, Na/HCO3- move into interstitium via Na/K ATPase and cotransporters
Cl- is not reabsorbed; Cl- concentration rises through this section
Sodium reabsorption in late PCT
2 mechanisms:
1) coupled Na/H and Cl/HCO3- antiporters
2) Paracellular passive diffusion
Driven by Cl- concentration gradient (high in lumen) established in early PCT
Water reabsorption in PCT
Movement of Na, Cl, HCO3- into interstitium establishes osmotic gradient for water to move out of lumen –> interstitium and into blood
PCT is highly permeable to water, moves from lumen –> blood via paracellular/transcellular pathways
Hormones affecting PCT
Angiontensin II: increase water and NaCl reabsorption
Adrenaline/noradrenaline: increase water and NaCl reabsorption
Dopamine: decrease water and NaCl reabsorption
Thin descending limb
“concentrating segment”
water permeable, solute impermeable
water moves out of filtrate, increasing concentration of filtrate
15% of water reabsorbed here
Thick ascending limb
“Diluting segment”
water impermeable
25% of Na+, Cl-, K+ reabsorbed here
Thick ascending limb transporters
NKCC:
- 2 Cl-, 1 Na+, 1K+ into cell from lumen
- Na+ moved into interstitium by Na+/K+ ATPase
- NKCC associated with ROMK: allows K+ to move from cell –> lumen, creates K+ gradient that helps drive NKCC channel
- also established positive charge in lumen, which drives other cations of urine into blood
Na+/H+ exchanger
Paracellular movement of ions
Hormonal effects on Loop of Henle
Aldosterone: increase NaCl absorption
Adrenaline: increase NaCl absorption
DCT
Reabsorbs ~7% of NaCl
secretes variable amounts of K+ and H+
water impermeable, remains a diluting segment
Transporters in DCT
NaCl cotransporter (NCC)
- moves 1 Na+ and Cl- into cell from lumen
- not associated with ROMK, so no electropositivity established in urine to drive other cation diffusion
Hormonal regulation of DCT
Aldosterone
Adrenaline
ADH: increase water reabsorption
Collecting duct
makes final decisions about salt and water balance
determination of pH in urine
Cell types in CD
1) principal cells
- have ENaC (epithelial sodium channels) - moves Na+ into cells from urine
- have ROMK: moves K+ into urine from cell, in response to negative lumen due to sodium movement
2) Intercalated cell
- response for acid-base balance
- determine acid-base balance by secreting/reabsorbing H+ and bicarbonate
Hormonal effects in CD
Aldosterone: increase chance of ENaC being open - increase water and NaCl reabsorption
Adrenaline
ADH: increase # of ENaC receptors available, increase water reabsorption
ANP: decrease # ENaC receptors available, decrease water/NaCl reabsorption
Urodilatin: decrease water/NaCl reabsorption
Urodilatin
secreted by DT/CD (not present in systemic circulation)
due to increase in ECFV
acts on CD
decrease NaCl/water reabsorption
Dopamine
released by dopaminergic nerves in the kidney, also synthesized by cells of PT (oppose action of adrenaline/NA)
Due to increased ECFV
acts on PT to decrease water/NaCl reabsorption
Other hormonal regulators
PG: PGI2 mainly
- afferent arteriolar vasodilation + natriuresis
- low ECFV: PGI2 rises to maintain renal perfusion, despite SNS activation & high AII
- giving NSAIDs to these patients can reduce PGI2 levels, cause renal failure
Uroguanylin: released in response to salt intake
- inhibits salt reabsorption in kidneys
NO: some diuretic properties
ADH
2 receptors:
V1 - v/c in arterioles, also found in brain/mesangial cells
V2 - CD cells and cause water resorption
Stimulated by:
- increasing osmolality in blood
- volume depletion
- vomiting/diarrhea
- pain
- exercise
- medications (narcotics, chlorpropamide, carbamapezine)
Diluting urine
Solute reabsorption without water
- ascending limb
- DT and CD in the absence of ADH
1) PT - isoosmotic resorption
2) descending limb - only permeable to water (concentrates urine)
3) thin ascending limb - impermeable to water, NaCl leaves urine, urea enters urine
- more NaCl leaves than urea enters - dilution
4) Thick ascending limb - impermeable to water and urea; active resorption of NaCl, urine leaving segment is hypo-osmotic with regards to plasma
5) DT and cortical CD: active resorption of NaCl, no water resorption in the absence of ADH
6) Medullary CD: active resorption of NaCl, small amount of water resorption in the absence of ADH
- in the absence of ADH, can get very dilute urine (50 in kids, 100-200 in elderly)
Concentrating urine
Water is never pumped, only diffuses
Kidney makes a hyperosmotic “sink” in interstitium to pull water out of urine, accomplished by thick ascending limb of LOH
1) PT to thick ascending limb: TAL extremely important in creating hyperosmotic interstitium to pull water out in medullary CD
- action of NKCC and Na/K ATPase
- countercurrent multiplication
2) DT and cortical CD: hypoosmotic filtrate
- ADH presence: presence of aquaporins - water filters out of urine
- can be concentrate to ~290 mosm/ kg water
- composition: less NaCl, more creatinine, urea, ammonia, K+
3) Medullary CD: osmolality of interstitium increases as moves down into medulla
- ADH: makes this permeable to water
- urine can be concentrated to ~1200 mosm/kg
Posm equation
2[Na+] + glucose + urea
