Renal Regulation of water & acid-base balance Flashcards
What is Osmotic pressure dependent on?
number of solute particles
How do you work out Osmolarity?
Concentration X number of dissociated particles.
e.g osmolarity of 100 mmol/L NaCl = 200 mOsm/L
What percentage of body weight is body fluid volume?
60%
How is body fluid volume split between intracellular and extracellular fluid?
2/3 Extracellular
1/3 Intracellular
What percentage of Intracellular fluid is Intravascular?
25%
Where is most extravascular bodily fluid found?
95% Interstitial Fluid
5% Transcellular Fluid
Give examples of Regulated & Unregulated water loss
Regulated - Renal regulation (urine production)
Unregulated - Sweat, Faeces, Vomit, Water evaporation from respiratory lining and skin.
Outline Positive water balance
1 - High water intake
2 - Increased ECF volume, decreased osmolarity and [Na+ ]
3 - Hypoosmotic urine production
4 - Osmolarity normalises
Outline Negative water balance
1 - Low water intake
2 - Decreased ECF volume, increased osmolarity and [Na+]
3 - Hyperosmotic urine production
4 - Osmolarity normalises
What percentage of water is reabsorbed in the proximal convoluted tubule?
67%
What cannot be absorbed in the thin ascending limb of the loop of Henle?
Water
What is passively absorbed in the thin ascending limb of the loop of Henle?
NaCl
What is actively absorbed in the thick ascending limb of the loop of Henle?
NaCl
What is passively absorbed in the descending loop of Henle?
Water
15%
What cannot be absorbed in the descending loop of Henle?
NaCl
What allows the passive absorbtion of water in the descending loop of Henle and collecting duct?
A hyperosmotic medullary interstitium and a gradient across the medulla.
What process creates a gradient in the medullary interstitium?
Countercurrent multiplication
Describe Countercurrent multiplication?
Active salt reabsorption from the ascending loop of Henle into the medullary interstitium increases osmolarity in the descending loop of Henle, leading to passive water reabsorption across the gradient.
Describe Urea Recycling?
Urea is transported into the medullary instertitium via UT-A1&3 in the collecting duct and then enters the descending loop of Henle via UT-A2, thus increasing the instertitium osmolarity and increased water reabsorption.
Urea Concentration occurs and urea excretion requires less water.
What is the role of Vasopressin in Urea Recycling?
Boosts UT-A1 &UT-A3 numbers.
Where does fluid enter first in the body?
Extracellular fluid.
Where is Vasopressin produced?
Hypothalamus (neurons in supraoptic ¶ventricular nuclei)
Where is vasopressin stored?
Posterior Pituitary
What is the effect of increased Plasma osmolarity on ADH?
Stimulates production & release
What is the effect of decreased Plasma osmolarity on ADH?
Inhibits production & release
What is the effect of Hypovolemia, decreased blood pressure on ADH?
Stimulates production & release
What is the effect of Hypervolemia, increased blood pressure on ADH?
Inhibits production & release
What are some factors that stimulate ADH production & release?
Nausea, Angiotensin 2, Nicotine
What are some factors that inhibit ADH production & release?
Ethanol, Atrial natriuretic peptide
Describe the mechanism of action of Vasopressin (ADH)
ADH reaches collecting duct via blood capillaries and binds to V2 receptor, activating G protein mediating cascade, activating Protein Kinase-A, this increasesthe secretion of aquaporin 2 channels which are transported and intserted int the apical membrane. Water can then be absorbed via aquaporin2 and then aquaporin 3&4 into the blood stream.
ADH can the up/downgrade the number of AQP2 &AQP3 numbers on either membrane as required.
What term describes excretion of concentrated urine in low volumes?
Antidiuresis
How does ADH increase sodium reabsorbtion?
Thick ascending limb: ↑Na+ - K+ - 2Cl- symporter
Distal convoluted tubule: ↑Na+ - Cl- symporter
Collecting duct: ↑Na+ channel
What is the effect of Central Diabetes Insipidus?
Decreased/negligent production of ADH, presents with polyuria, polydipsia, treat with external ADH supplementation.
What is the effect of Syndrome of inappropriate ADH secretion?
Increase Production and release of ADH, presents with Hyperosmolar urine, Hypervolemia, Hyponatremia, treat with non-peptide inhibitor of ADH receptor (conivaptan & tolvaptan)
What is the effect of Nephrogenic Diabetes Insipidus?
Less/mutant AQP2, Mutant V2 receptor, polyuria, polydipsia, treat with Thiazide diuretics + NSAIDs
Is it true or false that the blood of a patient suffering from Syndrome of inappropriate ADH secretion will slowly get more hyperosmotic?
False
Is it true or false that there is a net addition of metabolic acid that needs to be neutralised?
True
What is the role of the kidney in Acid-base balance?
Secretion & excretion of H+
Reabsorption of HCO3-
Production of new HCO3-
HCO3- needs to be replenished or we will run out of it
What equation demonstrates the relationship between [HCO3-] and partial pressure of CO2?
Hendersson-Hasselbach
[𝑯+]= (𝟐𝟒 𝐱 𝑷𝑪𝑶𝟐)/([𝑯𝑪𝑶𝟑−])
What indicates the source of an Acid-base disorder being Respiratory or Metabloic?
PCO2 - Respiratory
[HCO3-] - Metabolic
What percentage of bicarbonate ions are absorbed in the kidney?
Almost 100% 80% PCT 10% Ascending loop of Henle 6% DCT 4% CT
Describe the reabsorption of bicarbonate ion in the Proximal convoluted tubule
CO2 enters by diffusion from the tubular fluid side, in the presence of carbonic anhydrase it yields a proton and a bicarbonate ion, the proton ion can leave the cell and enter the tubular fluid via H+ATPase pump orNa+-H+antiporter, Bicarbonate ion goes into the blood via Na+-K+-ATPase pump or Na+-HCO3-symporter. H+ + HCO3- form carbonic anhydrase in the tubular fluid which forms water and C02, this CO2 molecule enters the PCT cell and as describe above leads to the loss of a bicarbonate ion into the bloodstream.
What are the different types of cells in the DCT & CT?
⍺-Intercalated cell: HCO3- reabsorption & H+ secretion.
β-Intercalated cell: HCO3- secretion & H+ reabsorption
Describe the mechanism of action in the ⍺-Intercalated cell
H+ is pumped into the tubular fluid via H+ATPase pump &H+K+Atpase pump and HCO3- leaves via the Cl-HCO3- antiporter
Describe the mechanism of bicarbonate ion production in the Proximal convoluted tubule
Glutamine is converted into 2 ammonia and 1 divalent ion which gives 2 HCO3-, which are reabsorbed. However you must get rid of the ammonia ion, which could reach the liver if it entered the bloodstream and become urea and proton ions which will require a bicarbonate ion to nullify it. So ammonia must be excreted by Na+H+antiporter into tubular fluid or becoming ammonia gas and leaving the cell via the tubular fluid membrane protein.
Describe the gain of new bicarbonate ions in the ⍺-Intercalated cell
H+ is neutralised by a phosphate ion, hence the bicarbonate ion produced and absorbed by the blood is a net gain of bicarbonate ion.
What happens in Metabolic Acidosis?
Decreased HCO3-, pH.
Hyperventilation and increased bicarbonate ion reabsorption and production.
What happens in Metabolic Alkalosis?
Increased HCO3-, pH.
Hypoventilation and increased bicarbonate ion secretion.
What happens in Respiratory Acidosis?
Increase pCO2 decreased pH.
Acute response - Intracellular buffering
Chronic Response - Increased HCO3- reabsorption and production.
What happens in Respiratory Alkalosis?
Decreases pCO2, Increased pH.
Acute response - Intracellular buffering
Chronic response - decreased bicarbonate reabsorption and production.
