Renal regulation of water and acid-base balance Flashcards
What is osmotic pressure directly proportional to?
number of solute particles (pulls fluid in)
What is osmolarity?
- concentration x number of DISSOCIATED particles
- osm/L or mOsm/L - e.g. 100mmol/L NaCl… osmolarity= 100 x2= 200 mOsm/L (double molarity bc NaCl dissociates)
What is the distribution of body fluid (i.e. intracellular, extracellular etc…)?
- 2/3 is intracellular fluid - 1/3 is extracellular fluid - of extracellular: 1/4 in plasma (intravascular) and 3/4 extravascular (outside capillary wall) - of extravascular: 95% interstitial fluid (surrounds cells/tissues) and 5% transcellular fluid (e.g. CSF, synovial fluid…)
What are examples of unregulated water loss?
- sweat - faeces - vomit - water evaporation from respiratory lining and skin
How is positive water balance regulated (e.g. if you drink a lot of water)?
- high water intake - leads to inc. ECF volume (water enters extracellular first) –> dec. Na+ conc. –> dec. osmolarity - kidneys produce hypo osmotic urine (dilute) –> osmolarity normalises
How is negative water balance regulated (e.g. dehydration)?
- low water intake - leads to dec. ECF volume –> inc. [Na+] –> inc. osmolarity - kidneys produce hyper osmotic urine (to preserve body’s water) –> osmolarity normalises - N.B. also triggers thirst
What is the difference in reabsorption between the descending and ascending loop of Henle?
- in descending loop–> salt not absorbed, but water is passively reabsorbed into medullary interstitium - in ascending loop–> water not reabsorbed, but salt passively (thin) and actively (thick) reabsorbed
How do we create a hyper osmotic medullary interstitium?
COUNTERCURRENT MULTIPLICATION - filtrate arrives at loop of Henle at 300 mOsm/L - then salt is ACTIVELY reabsorbed from the thick ascending loop–> lowering filtrate osmolarity and increasing interstitium osmolarity - then water passively flows out of thin descending limb to equilibrate w/interstitium–> so osmolarity in descending limb increases - this continues as more filtrate arrives–> a top-bottom gradient develops- 300-1200 mOsm/L ALSO urea recycling
What are the 2 urea transporters in collecting ducts?
- UT-A1 on apical cell membrane - UT-A3 on basolateral cell membrane - they pump urea out into the medullary interstitium (osmolarity can reach 600mmol/L)
Where can the urea in the medullary interstitium be reabsorbed and what transporters are involved?
- vasa recta via UT-B1 - loop of Henle at thin descending side via UT-A2
What is the purpose of urea recycling in the nephron?
- raises interstitium osmolarity, helping water reabsorption–> urine concentration - also means that urea excretion requires less water leaving the body and we can conserve this extra fluid
What effect does vasopressin have on urea reabsorption the transporters UT-A1 and UT-A3?
increases the number of UT-A1 and UT-A3 transporters–> increasing the permeability of the collecting duct to urea –> inc. osmolarity of medullary interstitium (indirectly leads to more water reabsorption–> ‘anti-pee’)
What is the main function of vasopressin/ADH?
to promote water reabsorption from the collecting duct
Where is vasopressin/ADH produced?
hypothalamus- neurons in supraoptic and paraventricular nuclei
Where is ADH stored?
posterior pituitary gland
What factors influence ADH production and release?
- inc. plasma osmolarity detected by osmoreceptors (v. sensitive) in hypothalamus–> inc. ADH - hypovolemia/dec. bp detected by baroreceptors–> inc. ADH to conserve water - nausea and vomiting stimulate ADH release - angiotensin II stimulates ADH release - nicotine stimulates ADH release - ethanol inhibits ADH prod/release - Atrial Natriuretic Peptide inhibits ADH prod/release
What is the mechanism of action of ADH in the principal cells of the collecting duct?
- ADH has arrived through blood vessel to principal cell - binds to V2 receptor on basolateral cell membrane–> G-protein mediated signalling cascade activated–> protein kinase A activated - pkA increases secretion of aquaporin 2 channels in vesicle form–> transported to apical cell membrane - water is reabsorbed through these AQP2 channels (can also go through AQP3- also regulated by ADH- /AQP4 channels at basolateral membrane)
What 3 transporters are present in the thick ascending limb of the loop of Henle and what do they do?
- Na+/K+ ATPase pump–> actively pumps 3 Na+ out (into blood) and K+ in - Na+/K+/2Cl- symporter (Na+ enters cell from tubular fluid due to conc. gradient) - K+/Cl- symporter –> they leave cell, reabsorbed by blood
What transporters are present at the DCT and what occurs?
NaCl actively reabsorbed - Na+/K+ ATPase pump at basolateral membrane - Na+/Cl- symporter (from tubular fluid to cell) - K+/Cl- symporter (from cell to blood)
How is sodium reabsorbed in the principal cells of the collecting duct?
through Na+/K+ ATPase pumps–> sodium reabsorbed into blood
Where are AQ2 channels present in the nephron (if there is ADH)?
DCT and collecting duct
What occurs in central diabetes insipidus (cause, features+treatment)?
- decreased/negligent production and release of ADH - acquired or genetic - low ADH, so polyuria and therefore polydipsia - treatment w/external ADH
What is syndrome of inappropriate ADH secretion (SIADH) (cause, features+treatment)?
- increased production and release of ADH - acquired or genetic - hyperosmolar urine, hypervolemia, hyponatremia (bc of high blood volume) - treatment w/ non-peptide inhibitor of ADH receptor (conivaptan + tolvaptan)
What is nephrogenic diabetes insipidus (cause, features+treatment)?
- correct amount of ADH produced, but mutant V2 receptor (acquired or genetic)–> so ADH can’t bind OR mutant AQP2–> so not enough/correct AQP channels - polyuria and polydipsia - treatment w/thiazide diuretics (reduce rate of filtration, so less urine) + NSAIDs
How does our body neutralise metabolic acid?
- bicarbonates neutralise acids - lungs get rid of the CO2 produced
What are the roles of the kidneys in terms of maintaining acid-base balance?
- secretion and excretion of H+ - reabsorption of HCO3- - production of new HCO3-
What can we deduce from the Henderson-Hasselbalch equation?
- when pp of CO2 rises in body–> [H+] increases–> acidosis - when pp of CO2 drops in body–> [H+] decreases–> alkalosis - [H+] is inversely proportional to [HCO3-], so if bicarbonate increases, H+ decreases–> alkalosis (and the opposite is true)
Where is the most bicarbonate reabsorbed in the nephron?
80% is reabsorbed in PCT
What transporters are involved in the reabsorption of bicarbonate at the PCT and how does it work?
- Na+/H+ antiporter (NHE3)–> uses downhill energy released by sodium entering cell to transport H+ into tubular fluid - H+ ATPase pump (V-ATPase)–> pumps out H+ into tubular fluid N.B. the H+ and HCO3- in the tubular fluid form water+CO2 due to carbonic anhydrase–> CO2 enters cell by diffusion–> then forms H+ and HCO3- due to CA in the cell (so then HCO3- can go into blood) - Na+/HCO3- symporter (NBC1)–> pumps out Na+ and HCO3- into blood from cell
What type of intercalated cell (alpha or beta) is involved in HCO3- reabsorption and H+ secretion?
alpha
What type of intercalated cell (alpha or beta) is involved in HCO3- secretion and H+ reabsorption?
beta
What transporters are present in alpha intercalated cells in the DCT and collecting duct and what do they do?
- H+ ATPase pump- H+ pumped out of cell into tubular fluid
- H+/K+ ATPase pump- H+ pumped out of cell into tubular fluid
- Cl-/HCO3- antiporter- HCO3- leaves cell and enters blood
N.B. carbonic anydrase converts H+ and HCO3- into CO2+H20 and vice versa (CO2 is absorbed into the cell from tubular fluid)
What transporters are present in beta intercalated cells in the DCT and collecting duct and what do they do?
- Cl-/HCO3- antiporter at apical cell membrane–> transports HCO3- into tubular fluid
- H+ ATPase pump at basolateral cell membrane–> pumps H+ into blood
- N.B. important during alkalosis
How are ‘new’ bicarbonate ions produced in the body?
- ammoniagenesis: glutamine produces 2NH4+ and A2-, which becomes bicarbonate–> absorbed into blood
- alpha-intercalated cells in DCT and collecting duct release H+ ions into tubular fluid–> neutralised by phosphate (or other) urinary buffer (not by bicarbonate), so the bicarbonate ion produced in the cell + transported into blood is essentially a new bicarbonate ion
How are the ammonium ions produced by glutamine in the PCT transported to the tubular fluid?
- Na+/H+ antiporter: Na+ in, NH4+ out into tubular fluid
- also NH3 dissolves out as gas, and is then protonated–> NH4+ (excreted by kidney)
How does the body compensate for metabolic acidosis?
- metabolic acidosis: dec. bicarbonate–> dec. pH
- compensatory response: hyperventilation to dec. CO2–> dec. H+ / inc. pH and kidneys inc. bicarbonate reabsorption and production (long-term)
How does the body compensate for metabolic alkalosis?
- metabolic alkalosis: inc. bicarbonate–> inc. pH
- compensatory response: hypoventilation–> inc. CO2–> inc. H+/ dec. pH and kidneys inc. bicarbonate excretion (long-term)
How does the body compensate for respiratory acidosis?
- respiratory acidosis: inc. CO2–> dec. pH
- compensatory response: intracellular buffering- carbonic anhydrase releases bicarbonate from CO2+water, which balances out pH in blood (acute) and kidneys inc. bicarbonate reabsorption and production (chronic)
How does the body compensate for respiratory alkalosis?
- respiratory alkalosis: dec. CO2–> inc. pH
- compensatory response: intracellular buffering- shift carbonic anhydrase reaction to left, producing more CO2–> dec. pH (acute) and kidneys dec. HCO3- reabsorption and production (chronic)
