1b Regulation of Water and Acid / Base Flashcards
What is osmotic pressure proportional to ?
the number of solute particles
What is the formula for osmolarity?
Concentration * number of dissociated particles
what is osmosis?
The movement of solute particles from an area of low concentration to an area of high concentration, across a semi permeable membrane
What proportion of the bodies fluid is intracellular and extracellular?
1/3 is ECF
2/3 is ICF
Of the Extracellular fluid, what proportion is intravascular and extravascular?
Intravascular = 25%
Extravascular = 75%
What are the four ways in which water leaves the body in an unregulated sense?
Sweat
Faeces
Vomit
water evapouration from respiratory lining and skin
What is the regulated method of water loss from the body?
renal regulation = urine production
Describe how renal regulation will normalise the osmolarity when there is a high water intake?
High water intake
Higher ECF volume, Lower Sodium conc.
Lower osmolarity
Hypoosmotic urine production
Osmolarity normalised
What is the first compartment which water enters into once it enters into the body?
ECF
Describe how renal regulation will normalise the osmolarity when there is a low water intake?
Low water intake
Lower ECF volume, Higher Sodium conc.
higher osmolarity
Hyperosmotic urine production
Osmolarity normalised
What does water require in order to be absorbed passively?
A gradient
What is the osmotic status of the medullary interstitium?
The medullary interstitium needs to be hyperosmotic for water reabsorption to occur from the Loop of Henle and Collecting Duct
What is /isnt absorbed in the descending loop of henle?
Water is passively reabsorbed
Salt is not reabsorbed
What is / isn’t absorbed in the ascending loop of henle?
Active and passive reabsorption of Salt
No Water reabsorption
Where does ADH act?
On the collecting duct and distal convoluted tubule
Describe the process of concurrent multiplication?
- Active Salt reabsorption
- Passive water reabsorption
Firstly, there is active salt reabsorption from the thick ascending limb of the LOH. That leads to an increased salt conc. in the intermedullary interstitium —> water from the descending limb leaves the descending limb by osmosis.
Tubular fluid then reaches the thin ascending LOH and it is hyperosmolar and this means salt must passively be reabsorbed to reduce the osmolarity of the tubular fluid
Then the new filtrate arrives at the descending limb and the process starts again. There is multiplication each time it occurs.
What does counter-current multiplication generate?
Forms a gradient from the top of the loop of Henle to the bottom in the medullary interstitium
Describe the process of Urea recycling
- Urea enters into the
collecting duct - Some leaves via the UT-A1 (Apical membrane) and UT-A3 (Basolateral) transporters into the medullary interstitium
- Then, the urea is either reabsorbed into the blood (Vasa Recta) through the UT-B1 transporter, or reabsorbed into the THIN DESCENDING LIMB using UT-A2
What is the result of Urea recycling?
- Urine concentration occurs
- Urea excretion requires less water
Describe the effect of vasopressin in Urea recycling?
Vasopressin boosts UT-A1 and UT-A3 numbers
Which membrane is UT-A1 in?
Apical
Which membrane is UT-A3 in?
Basolateral
What is the main function of ADH?
Promote water reabsorption from the collecting duct
Where is ADH stored?
Posterior Pituitary
Where is ADH produced?
Hypothalamus (neurones in supraoptic and paraventricular nuclei)
What are the main stimulatory factors for ADH release?
Increased plasma osmolarity
Decreased blood pressure
Nausea
Angiotensin II
Nicotine
What are the main inhibitory factors for ADH production and release?
decreased plasma osmolarity
Hypervolemia = high blood pressure
Ethnaol
Atrial Natriuretic Peptide
What percentage change in blood pressure is required for detection by baroreceptors?
5-10%
What detects the fluctuation in plasma osmolarity?
osmoreceptors in the hypothalamus
Describe the mechanism of action of ADH?
ADH binds to V2 receptor
Binds G protein
This activates Adenylate cyclase - ATP-> cAMP
This activate protein kinase A
This leads to increased vesicle transport of Aquaporin 2 molecules to the apical membrane
Water then reabsorbed into the blood through AQP2 on the apical and AQP3 and AQP4 on the basolateral side into the blood
What is meant by diuresis?
Increased dilute urine excretion
During diuresis, how much ADH is present
Zero or small amounts
Describe how the reabsorption of salt in the thick ascending limb of the LOH happens?
What channels?
Na+ K+ ATPase Pump on basolateral side pumps Na+ into blood
K+ Cl+ Symporter on basolateral - pumps both into the blood
Na+ k+ 2Cl- symporter on the apical side
All work to increase the absorption of Na and Cl into the blood
How much water and salt is reabsorbed into the proximal collecting duct?
2/3 of salt and water
The fluid which comes out the LOH is what osmotic state?
Hypoosmotic
Describe how reabsorption in the distal convolute tubule contributes to diuresis?
Active Na + Cl reabsorption through ATPase pumps and symporters
Describe how reabsorption in the principal cells contribute to diuresis
Interms of pumps
Na+ K+ ATPase Pumps pump sodium into the blood
Some water reabsorption into blood via paracellular pathways (as no ADH so no AQP) to counteract
What type of urine is produced during diuresis?
Hypoosmotic - dilute urine, alot of water
What is meant by anti-diuresis?
When concentrated urine is produced (low volumes)
How much ADH is present in state of anti-diuresis?
Alot
What are the three ways in which ADH supports Na+ reabsorption?
1, Thick ascending limb = increasing Na+ K+ 2Cl- symporter
- Distal convoluted tubule = increased Na+ Cl- symporter
- Collecting duct = Increasing Na+ channels
What are the three ADH related clinical disorders?
ADH Insufficieny
SIADH
ADH Resistance
What is the cause of ADH Insufficiency?
Decreased production / release of ADH
What are the clinical features of ADH Insufficiency?
Polyuria and PolyDipsia
What is the treatment for ADH Insufficiency?
external ADH ike desmopressin or ddAVP
What is the cause of SIADH?
Increased production and release of ADH
What are the clinical features of SIADH?
Hyperosmolar urine
Hypervolemia
Dilutional Hypoatremia due to all the water which is being absorbed
What is the treatment for SIADH?
Non-peptide inhibitor of ADH receptor (Conivaptan & Tolvaptan)
What is the cause of ADH Resistance?
Less / mutant AQP2
Mutant V2 receptor
What are the clinical features of ADH Resistance?
Polyuria and Polydipsia
What is the treatment for ADH Resistance?
Thiazide diuretics + NSAIDs
Describe how there is a net addition of metabolic acid in the body?
Diet + Metabolism -> Acid + Base -> Base then excreted in the faeces
How is metabolic acid neutralised?
Through the bicarbonate buffer system
what is the problem with the bicarbonate buffer system?
Only a certain amount of bicarbonate in the ECF compartment, therefore has to be replenished
How do the kidneys have a role in acid base regulation?
Reabsorption of Bicarbonate
Production of new bicarbonate
If the cause of an acid base disorder is the partial pressure of carbon dioxide, what is the type of disorder?
respiratory disorder
If the cause of an acid base disorder is the concentration of bicarbonate, what is the type of disorder?
Metabolic
Which part of the kidneys is most of the bicarbonate absorbed into?
The proximal collecting tubule
What is the enzyme which is needed to convert carbon dioxide into bicarbonate?
Carbonic anhydrase
Describe how bicarbonate is reabsorbed into the proximal convoluted tubule?
HCO3- is reabsorbed via the Na+ HCO3- symporter (3 x HCO3- for each Na+)
H+ back into the tubular fluid through Na+ - H+ antiporter (NHE3) and H+ ATPase pump (V-ATPase Pump)
How does CO2 enter into the cells of the kidney?
Diffusion
What happens in the alpha intercalated cells of the distal convoluted tubule?
HCO3- reabsorption and H+ secretion
What happens in the beta intercalated cells of the distal convoluted tubule?
HCO3- secretion and H+ reabsorption
Which cells of the distal convoluted tubule are active during alkalosis?
Beta cells
Which cells of the distal convoluted tubule are active during acidosis?
Alpha intercalated
How is bicarbonate reabsorbed in the alpha intercalated cells?
Cl- HCO3- antiporter
How is bicarbonate excreted in the B-intercalated cells?
Through the Cl- HCO3- anti-porter on the apical side (into the tubular fluid)
What needs to happen in the proximal convoluted tubule in order for new bicarbonate production to occur?
The ammonia which is generated as a result of the breakdown of Glutamine needs to be removed, otherwise they will just neutralise the bicarbonate produced
What buffer system helps new bicarbonate to be produced in the distal convoluted tubule?
Phosphate buffer system
How is new bicarbonate produced in the distal convoluted tubule?
Alpha intercalated cell as well
CO2 diffuses into the cell and H+ and HCO3- is produced
Bicarbonate is absorbed into the blood via the Cl- and HCO3- anti-porter
The H+ leaves the alpha intercalated cell into the tubular fluid thorugh H+ ATPase pumps and H+ K+ ATPase, and then reacts to forms phosphoric acid, so is buffered.
What are the characteristics of metabolic acidosis?
Low bicarbonate and Low pH
What are the characteristics of metabolic alkalosis?
high bicarbonate and high pH
What are the characteristics of respiratory acidosis?
High pCO2 and Low pH
What are the characteristics of respiratory alkalosis?
Low pCO2 and High pH
Describe the compensatory response to metabolic acidosis?
respiratory compensation - Hyperventilation, so pCO2 decreases, H+ decreases and HCO3- reabsorption and production increases
Describe the compensatory response to metabolic alkalosis?
respiratory compensation - Hypoventilation, so pCO2 increases, H+ increases and HCO3- excretion increases
What is the acute compensatory mechanism which occurs in response to respiratory acidosis?
Intracellular buffering, where the H+ ions are neutralised by cellular proteins eg phosphate buffer system
A patient reported to his GP complaining of stomach bloating, swelling in legs, headache, and fatigue. Urine dipstick test results showed high specific gravity, and further urine analysis showed high [Na+]. Blood tests showed decreased plasma [Na+]. What is the most plausible diagnosis and treatment?
Syndrome of Inappropriate ADH release, treat with non-peptide inhibitor of ADH
What is the compensatory mechanism for chronic respiratory acidosis?
Increased bicarbonate reabsorption and production
What is the compensatory mechanism for chronic respiratory alkalosis?
Decreased bicarbonate reabsorption and production