What is the time course of events if a man suddenly ate a very high sodium diet.
- Salt would change his plamsa omsolality.
- He would try compensate for that by excreting salt but this lags by a day or so.
- So in the meantime he needs to find another way to balance (the increased Na+ in his ECF), and this is done through increased water intake/reabsorbtion (inc thirst). This can be done very quickly.
Plasma osmolality returns to normal but at the expense of larger ECF volume
Free water (no salt) is_______, Saline is regulated _______.
Why is this?
Free water (no salt) is cleared rapidly, Saline is regulated much slower.
Free water: His total water volume wil increase, both in ICF and ECF and will dilute his salt slightly, and suddenly he will have a huge spike in peeing do to kidneys sensing lowered osmo.
Saline: (same osmo/isotonic as body fluids) as we haven't actually diluted, just changed the volume (that has a 15% buffer), theres a very little increase in urine and he will retain fluid.
Glucose is NOT salt. If you give a patient glucose, what are you actually giving them?
You are giving them water. Although iso-osmotic when it goes in, glucose is metabolised to water (or bound to glycogen) so you are effectively diluting all compartments
Eg: 5% dextrose ~280mOsm glucose
What do specific IV fluids do?
Isotonic Saline fluids (normal): temporarily expand ECF
Hypotonic Saline fluids (NaCl): expand ICF
Controlled principally by:
What is the consequence of this having a much larger range then the osmolality?
Because the osmolality of the ECF is kept relatively constant (between 1-2%), the amount of Na+ in the body determines the volume of the ECF.
In order to maintain a constant ECF volume, our Na+ excretion must
Match Na+ input by the diet.
Na+ out = Na+ in
This shows us the amount that is retained through each segment.
Whats reabsorbed by the end of the Proximal Tubule?
100% of glucose reabsorbed
2/3 of Na+, Cl-, K+ and water reabsorbed
pH is more acidic @ 6.7
Whats been reabsorbed by the end of the Loop of Henle?
More Na+, Cl-, K+ and water has been reabsorbed.
Because LOH is for water reabsorbtion
What's happening is the Distal tubule and collecting duct? Whats left
More reabsorbtion of Na+, Cl-, water .
Filtration of some K+ that is then excreted, pH drops further.
The balance of Hydrostatic and oncotic Pressures withing a semi-permeable capillary membrane.
Hydrostatic Pressure: forces water and solutes out of the blood
This is BALANCED by
Oncotic Pressures: due to plasma proteins that are not filtered and exert a pulling pressure inwards.
**Not entirely balanced, little bit of fluid out, collected by lympathic system.
How is the capillary tuft of the glomerulus different to other capillaries? Whats the NFP and how much is filtered?
- Much, much leakier due to the fenestrated endothelium.
- Its is also located between two arterioles (not art and ven)
NFP: 10mmHg and 150L/day
NFP and GFR in the glomerulus. What's the primary regulator of GFR?
NFP: +10 mmHg
~20% of total plasma volume in glomerular is filtered.
GFR: 125ml/min (for both kidneys)
In order for ECF osmo and pH to be maintained it needs to ensure constant GFR, and this is done by changing glomerular hydrostatic pressure.
What is the role of 'Renal Autoregulation'
To ensure that changes in systemic blood pressure don't cause changes in GFR. Maintains GFR from an MAP of 80-160mmHg.
- involves feedback mechanisms that cause either dilation or constriction of the afferent arteriole or constriction of the efferent arteriole. (think of Garden hose)
If you VASOCONSTRICT the afferent arteriole
What happens if you VASODILATE the afferent arterioles or moderately constrict the efferent arteriole?
(In constricted efferent arteriole this is due to slight back log)
What are the two mechanisms of Renal autoregulation and how do they work?
- Renin-angiotensin II: const of efferent arteriole (inc GFR)
- Atrial Naturietic Peptide (ANP and BNP): dilation of afferent arteriole (inc GFR)
Sympathetic Nervous system: Constriction of afferent arteriole (dec GFR)
- Myogenic: inc arterial P stretches afferent art. inducing constriction; offsets P inc and keeps GFR stable
- Tubuloglomerular feedback: Macula densa monitor salt levels of distal tubule, if high they signal to the afferent art. to constrict. ; decr GFR (returning GFR to stable point)
Flow diagram of Tubuloglomerular feedback
Flow diagram of Renin-Angiotensin Mechanism
Ensures both GFR and blood volume increases.
Draw the extensive flow diagram of when BP drops.
What are the Transport Mechanisms that drive so much reabsorption in the Proximal Tubule?
Transcellular (across epithelial cells)
- Primary active transport, ATP driven
- Secondary active transport, driven by another gradient
co-transport/symport or countertransport/antiport
Paracellular (between cells/passive)
Why is the proximal tubule loaded up with mitochondria?
- In PT the Na+ coupled transporters predominant, Na+/K+ ATPase function is critical (this consumes ~90% ATP).
Na+/K+ ATPase drives active solute uptake via sym/anti-porters.
eg: Na+-coupled glucose symporter, moves down conc gradient to pull glucose into cell
- Water follows Na+ paracellularly via leaky tight junctions (solvent drag)
When water follows salt (down its osmotic gradient) paracellularly some solutes are reabsorbed with this water (esp for K+)
Role of Bicarbonate?
- Important pH buffer (so needs to be reabsorbed)
- Can't diffuse across cell membrane
- So reabsorbtion depends of carbonic anhydrase which breaks it down into water and CO2 that can freely diffuse (in BB & cytoplasm)
This is why pH drops as we are trying to reclaim HCO-3
Steps of Bicarbonate reabsorbtion
- Na+ uptake drives H+ extrusion into lumen (lowers pH)
- This drives reabsorbtion of HCO3- via carbonic anhydrase as CO2
- In cytosol CA converts back to H+ and HCO3- (some CO2 generated)
- HCO3- transported across basolateral membrane via trnasporters, ~90% reabsorbed
Proximal Tubule dysfunction can cause?
Proximal Tubule (mediated) acidosis
How does the PT generate new Bicarbonate?
Glutamine metabolised to NH4+and bicarbonate
NH4+: to lumen via Na+/H+ exchanger
Bicarbonate: to blood for acid/base buffering
Increased ECF [H+] increases this process ⇒ more HCO3-
Hereditary or Acquired syndrome, impaired ability of PT to reabsorb HCO3-, Pi, aa, glucose and low MW proteins. Leads to urinary excretion of these products.
Cl- reabsorbtion in the proximal tubule
Cl- becomes concentrated in late PT due to prior reabsorb of water and solutes early. Starts to move out paracellularly ⇒ lumen becomes more positive ⇒ Na+ paracellular reabsorbtion
Secretion in PT
Organic anion/cations. Important for clearing 'xenobiotic agents from diet, drugs etc.