Lecture 4: Glom and Tubular Function 1

Question 1

What is the time course of events if a man suddenly ate a very high sodium diet.

Answer 1

1. Salt would change his plamsa omsolality.
2. He would try compensate for that by excreting salt but this lags by a day or so.
3. 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.
4. Plasma osmolality returns to normal but at the expense of larger ECF volume

Question 2

Free water (no salt) is\_\_\_\_\_\_\_, Saline is regulated \_\_\_\_\_\_\_.
Why is this?

Answer 2

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.

Question 3

Glucose is NOT salt. If you give a patient glucose, what are you actually giving them?

Answer 3

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

Question 4

What do specific IV fluids do?

Answer 4

Isotonic Saline fluids (normal): temporarily expand ECF

Hypotonic Saline fluids (NaCl): expand ICF

Question 5

Osmolality.

Regulated by:
Controlled by:

Answer 5

.

Question 6

ECF volume

Regulated by:
Controlled principally by:

What is the consequence of this having a much larger range then the osmolality?

Answer 6

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.

Question 7

In order to maintain a constant ECF volume, our Na+ excretion must

Answer 7

Match Na+ input by the diet.

Na+ out = Na+ in

Question 8

This shows us the amount that is retained through each segment.

Answer 8

…

Question 9

Whats reabsorbed by the end of the Proximal Tubule?

Answer 9

100% of glucose reabsorbed

90% bicarbonate

2/3 of Na+, Cl-, K+ and water reabsorbed

pH is more acidic @ 6.7

Question 10

Whats been reabsorbed by the end of the Loop of Henle?

Answer 10

More Na+, Cl-, K+ and water has been reabsorbed.

Because LOH is for water reabsorbtion

Question 11

What’s happening is the Distal tubule and collecting duct? Whats left

Answer 11

More reabsorbtion of Na+, Cl-, water .

Filtration of some K+ that is then excreted, pH drops further.

Question 12

The balance of Hydrostatic and oncotic Pressures withing a semi-permeable capillary membrane.

Answer 12

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.

Question 13

How is the capillary tuft of the glomerulus different to other capillaries? Whats the NFP and how much is filtered?

Answer 13

1. Much, much leakier due to the fenestrated endothelium.
2. Its is also located between two arterioles (not art and ven)

NFP: 10mmHg and 150L/day

Question 14

NFP and GFR in the glomerulus. What’s the primary regulator of GFR?

Answer 14

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.

Question 15

What is the role of ‘Renal Autoregulation’

Answer 15

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)

Question 16

If you VASOCONSTRICT the afferent arteriole

Answer 16

Decreased GFR

Question 17

What happens if you VASODILATE the afferent arterioles or moderately constrict the efferent arteriole?

Answer 17

Increased GFR.
(In constricted efferent arteriole this is due to slight back log)

Question 18

What are the two mechanisms of Renal autoregulation and how do they work?

Answer 18

Extrinsic:

• 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)

Intrinsic:

• 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)

Question 19

Flow diagram of Tubuloglomerular feedback

Answer 19

..

Question 20

Flow diagram of Renin-Angiotensin Mechanism

Answer 20

Ensures both GFR and blood volume increases.

Question 21

Draw the extensive flow diagram of when BP drops.

Answer 21

Question 22

What are the Transport Mechanisms that drive so much reabsorption in the Proximal Tubule?

Answer 22

Transcellular (across epithelial cells)

1. Primary active transport, ATP driven
2. Secondary active transport, driven by another gradient
   * co-transport/symport or countertransport/antiport*

Paracellular (between cells/passive)

Question 23

Why is the proximal tubule loaded up with mitochondria?

Answer 23

• 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)

Question 24

Solvent drag?

Answer 24

When water follows salt (down its osmotic gradient) paracellularly some solutes are reabsorbed with this water (esp for K+)

Question 25

Role of Bicarbonate?

Answer 25

• 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

Question 26

Steps of Bicarbonate reabsorbtion

Answer 26

1. Na⁺ uptake drives H⁺ extrusion into lumen (lowers pH)
2. This drives reabsorbtion of HCO₃^- via carbonic anhydrase as CO₂
3. In cytosol CA converts back to H⁺ and HCO₃^- (some CO₂ generated)
4. HCO₃^- transported across basolateral membrane via trnasporters, ~90% reabsorbed

Question 27

Proximal Tubule dysfunction can cause?

Answer 27

Proximal Tubule (mediated) acidosis

Question 28

How does the PT generate new Bicarbonate?

Answer 28

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^-

Question 29

Fanconi Syndrome

Answer 29

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.

Question 30

Cl^- reabsorbtion in the proximal tubule

Answer 30

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

Question 31

Secretion in PT

Answer 31

Organic anion/cations. Important for clearing ‘xenobiotic agents from diet, drugs etc.