Uro - Renal regulation Flashcards
How do you calculate osmolarity
Number of dissociated solute particles x concentration - expressed as Osm/L or mOsm/L
How does osmotic pressure correlate with number of solute particles
Increase in solute particle number increases osmotic pressure - NOT SIZE
What is osmosis
Passive movement of water from an area of low solute concentration to high solute concentration across a semi-permeable membrane until they reach an equilibrium
How much of the body weight does fluid make up
60%
What is the split of ICF and ECF
2/3 ICF, 1/3 ECF - separated by cell membrane
What is ECF split into
3/4 extravascular, 1/4 intravascular (Plasma) - separated by capillary
What is extravascular split into
95% interstitial fluid, 5% transcellular fluid e.g. peritoneal fluid
What constitutes unregulated water loss
Sweat
Faeces
Vomiting
Water evaporation from the skin or respiratory lining
What makes up regulated water loss
Water loss from urine
How does osmolarity normalise in positive water balance
- Excess water intake
- ECF hit first - volume increases
- Dilution effect = sodium conc decreases
- Osmolarity decreases
- Hyposmotic urine production
- Osmolarity normalises
How does osmolarity normalise in negative water balance
- Low water intake
- ECF hit first - volume decreases
- Sodium concentration increases
- Osmolarity increases
- Hyperosmotic urine production
- Osmolarity normalises
Where is water reabsorbed in the nephron
67% reabsorbed in the PCT
It is then passively reabsorbed in the thin descending loop of henle (15%)
Then, variable amounts are reabsorbed in the DCT and CD - none is reabsorbed in the ascending LoH
What do we need in order for water to be passively reabsorbed in the loop of Henle and Collecting Duct
We need a hyperosmotic medullary interstitium
By what process do we create a hyperosmotic medullary interstitium
Countercurrent multiplication
Describe countercurrent multiplication
Tubular fluid arrives in the DLOH at 300 (arbitrary mOsm/L), and moves through until it reaches the thick ALOH where sodium is actively reabsorbed. This means that the tubular osmolarity decreases but medullary osmolarity increases. Due to the increase in medullary osmolarity e.g. to 400, tubular fluid now arriving in the DLOH will lose water passively to equalise osmolarity. Therefore the new tubular osmolarity in the DLOH = 400 too. AS tubular fluid moves through the LoH, Na is still actively reabsorbed in the thick ALOH, therefore we get multiplication of the process and a gradient will eventually form.
The reason as to why the top of the intersitum (outer) is less hyperosmotic is because when water first arrives in the DLOH it will move into the top of the interstium therefore the outer inertsitium will by more hypo osmotic
What gradient does countercurrent mutliplaction create
1200 in the inner medulla
300 in the outer medulla
What else occurs in the medulla to aid with water reabsorption
Urea recycling
How does urea leave the collecting duct
It can leave the collecting duct via UT-A1 and then UT-A3 - AVP boosts these transporters to concentrate urine
What is the medulla conc of urea
600mmol/L
What are the 2 fates of urea having entered the medullary interstitum
It can either enter the DLOH via UT-A2 or it can enter the vasa recta via UT-B1 - this means that urea is recycled in the nephron to increase the osmolarity of the medulla
What is the effect of urea recycling
Urea excretion requires less water
Urine concentration occurs
Describe ADH
Short protein hormone produced in the magnoceullar neurones of the supraoptic and paraventricular nuclei of the hypothalamus, and then stored in the PPG. The main function is to promote water reabsorption in the CD and concentration urine
What stimulates ADH
Increase in plasma osmolarity Decrease in blood volume Decrease in blood pressure Nausea Nicotine Angiotensin II
What inhibits ADH
Decrease in plasma osmolarity Increase in blood pressure Increase in blood volume Atrial natriuretic peptide Ethanol
What is a healthy plasma osmolarity
275-290 mOsm/kg H2O
What cells does ADH act on
Principal cells of the collecting duct
What is the mechanism of action for ADH
Binds to v2 receptors in the basolateral membrane of cells. V2 = G-coupled - stimulates adenylate cyclase to produce cAMP and thus protein kinase A. This leads to the secretion of AQP2 channels which insert into the apical membrane
ADH also regulates AQP-3 channels which are found on the basolateral membrane
How is sodium reabsorbed in the thick ascending limb
Active reabsorption whereby sodium is reabsorbed into the blood via Na/K ATPase, meaning that Na can enter the cells of the thick ascending limb passively through the triple pump - this provides energy for the entry of K and Cl too
How is sodium reabsorbed in the DCT
Na/K ATPase in basolateral side again but there is a Na/CL symporter an apical side
How is sodium reabsorbed in the principal cell of the CD
Na/K ATPase in basolateral, Na channel on apical side
How does ADH affect Na reabsorption
ADH supports Na reabsorption in the thick ascending limb, DCT and CD
Where does most water reabsorption happen in the CD
In the inner medulla due to the higher gradient as you move down
How do we get net addition of metabolic acid and how much per day
Through metabolism and diet, there is net addition of bases and acids, however due to excretion of bases through feces, there is an overall net addition of acids by about 50-100mEq/ day
How are metabolic acids neutralised
We have around 350mEq of HCO3 to neutralise H2SO4 and HCL which are the main metabolic acids
What is the role of the kidneys
Secretion and excretion of H+
Reabsorption of HCO3
Production of new HCo3 ions
What is the need to recycle HCO3 levels
Our body only has 350mEq // 24mEq/L therefore we only have a limited store that would run out in 4-7 days without replenishment therefore we need a way to conserve this
Where is bicarbonate reabsorbed
80% in PCT
10% in TALOH
6% in DCT
4% in CD
How is bicarbonate reabsorbed in the PCT
Co2 enters the cells of the PCT via diffusion
Co2 binds to water via carbonic anhydrase and then H+ +HCO3
H+ leaves the cell via H+ ATPase or via Na/H anti porter into the tubular fluid
HCO3 reabsorbed through the Na/HCO3 symporter
How is bicarbonate reabsorbed in alpha cells of the DCT and CD
Co2 enters the cells of the PCT via diffusion
Co2 binds to water via carbonic anhydrase and then H+ +HCO3
H+ leaves either via H+ ATPase or via K/H anti porter into the tubular fluid
HCO3 reabsorbed by Cl/HCO3 anti porter into the blood
How is bicarbonate secreted in the beta cells of the DCT and CD
H+ATPase allows H+ entry into blood
HCO3/Cl antiporter transports HCO3 into the tubular fluid
How do we produce new HCO3 ions in the PCT
Glutamine is broken down into 2NH4 and A2- (divalent ion that gives 2HCO3).
2HCO3 are reabsorbed into the blood, whereas NH4 can be pumped out via NH4/Na anti porter. Or, it can be broken down to HN3 + H. NH3 is a gas that leaves via diffusion; H+ leaves via Na/H anti porter and then NH3 and h+ rejoin in the tubular fluid to form NH4
How do we produce new HCO3 ions in the DCT and CD
HCO3/Cl anti porter allows HCO3 reabsorption whilst we have H+ secretion by HATPase or H/K ATPase and then neutralisation via the phosphate buffer system
What is the compensatory response for metabolic acidosis
Increase in ventilation - increase in HCO3 reabsorption and production
What is the compensatory response for metabolic alkalosis
Decrease in ventilation and increase in HCO3 excretion
What is the compensatory response for respiratory acidosis
Acute: intracellular buffering whereby H+ formed in cells of nephron are neutralised by cellular proteins to cause net gain of HCo3
Chronic: increase in HCo3 reabsorption and production
What is the compensatory response for alkalosis
Acute: intracellular buffering whereby we shift towards H2Co3 production so less HCo3 is also produced.
Chronic: decrease in HCo3 reabsorption and production
