Disorders Of Acid-base Balance

Question 1

Proximal tubule

Answer 1

Active reabsorption of multiple solutes

Metabolically active cells- lots of mitochondria
This energy is used to re absorb substances mainly from the urine and to actively excrete substances back out too through those tubular cells

Sodium gradient generated by Na/K ATPases

Vulnerable to hypoxia because they are very active and so need lots of oxygen and toxicity

Question 2

Reabsorbed solute

Answer 2

Glucose

Amino acids

Phosphate

Bicarbonate

Question 3

Renal glycosuria

Glucose reabsorption

Answer 3

There is a cotransporter that reaborbs sodium and glucose, driven by an active, metabolically driven sodium gradient which is generated by the Na/K/ATPase and the Sodium glucose transporter 2 (SGLT2)

Mechanism: failure of glucose reabsorption

Question 4

Aminoaciduria: Cystinuria

Amino acid reabsorption

Answer 4

Kidneys reabsorb free amino acids which are excreted out into the urinary space because they are needed

There are many amino acid transporters
An e.g. is the Renal basic amino acid transporter (rBAT)

If there is an error in this transporter, theres excess amino acids in the protein as they have not been reabsorbed.
In this case, excess cysteine leads to crystal formation and eventually stone formation

Question 5

Treatment of Cystinuria

Answer 5

High fluid intake: High urine flow rate- increase in the amount of water in urine causes lower concentration of crystallising substances and mechanical flow increases, so less likely for crystals to get big and stuck

Alkalise urine: increases solubility of cystine and so does not allow cystine to crystallise

Chelation: penicillamine, captopril
This is a drug that binds to the cysteine and stops it getting into the urine and stick in there

Surgery/ percutaneous treatment

Question 6

Hypophosphataemic rickets

Reabsorbing phosphate

Answer 6

Lack of mineralisation of bones because of a lack of phosphate because of loss of phosphate into the urine because of a lack of expression of the Sodium Phospahte contransporter in proximal tubule

Question 7

Bicarbonate reabsorption

Answer 7

There’s sodium and bicarbonate in the tubular lumen that needs to be reabsorbed
There is active sodium transport in the tubular cells
On the tubular lumen surface of the proximal tubular cells there is a sodium hydrogen anti porter

The sodium hydrogen anti porter is going to swap sodium for hydrogen ions
These H+ ions are going to be made in the tubular cell by combining water and carbon dioxide to carbonic acid and then splitting this into H+ and HCO3-
This is catalysed by the enzyme carbonic anhydrase which is CA

These hydrogen ions are split out into the tubular lumen and so theres carbonic anhydrase in the tubular lumen which then catalysed again that conversion back to water and CO2 which can be passively reabsorbed back into the cells
Essentially H+ ions are recycled through the tubular cell back into the lumen and back in again
The bicarbonate on the other hand gets reabsorbed along with sodium into the bloodstream
So the acid bicycles across the cell border, whereas the bicarb and the sodium get reabsorbed into the bloodstream
Dependant upon the carbonic anhydrase enzyme
This enables you to reabsorb a substantial amount of the bicarbonate load in the proximal tubule and a significant amount of sodium

Question 8

Proximal (type 2) renal tubular acidosis

Answer 8

Caused by a Defect in Na/H antiporter

Question 9

Carbonic anyhdrase

Answer 9

Allows more rapid compensation of respiratory alkalosis

Question 10

Fanconi syndrome

Answer 10

If many parts of the proximal tubule aren’t working together, then the driving problem is that the Na/K/ATPase that are providing the motor for the reabsorption have failed

This results in this mixed syndrome: fanconi syndrome

Question 11

Loop of Henle

Answer 11

Generates medullary concentration gradient

Active Na reabsorption in thick ascending limb

Also involved in other electrolyte reabsorption

This then enables you to develop higher osmotic concentration the deeper into the kidney you go
As the filtrate in the ascending limb becomes more dilute as the LoH ascends into the cortex, the concentration of the surrounding fluid increases so osmotic concentration gradient increases

This enables you to control the water excretion when you reach the collecting duct

Question 12

Thick ascending limb function

Answer 12

NKCC2- Sodium Potassium and 2 Chlorides (this is what it helps to reabsorb) on the tubular lumen

Potassium ion on the luminal surface which recycles the potassium back out so you’re not reabsorb in the K+ that’s getting cycled back out into the urinary space

Na/K/ATPase on the interstitial border

Chloride channels on interstitial border
Vital as without the ability for chloride efflux into the interstitial fluid, the process stops as then chloride accumulates intercellularly

All of these channels working together allows for the generation of an electrochemical gradient
This is because 1 Na+ an 2 Cl- are absorbed into the interstitial fluid which generates a negative electrochemical gradient that is going to drive calcium and magnesium reabsorption, paracellularly That driven by the electrochemical gradient created by the Na+ and Cl- reabsorption

All channels must work together to allow this to happen

Question 13

Distal tubule and collecting duct

Answer 13

Distal tubule and collecting duct allow ‘fine tuning’ of Na+ reabsorption, K+ and acid-base balance

Collecting duct mediates water reabsorption and urine concentration

Question 14

Gitelmans syndrome

Answer 14

Caused by defect in the NCCT channel which is in the distal tubule
This is responsible for sodium chloride reabsorption past the loop of henle in the early part of the distal tubule

Defect here causes failure to reabsorb NaCl and many more changes in reabsorptions

Question 15

Role of kidneys in control of blood pressure

Answer 15

Fall in BP causes the juxtaglomerular apparatus (which sits between kidney tubule and glomerulus) to tell the kidneys that you’ve reduced your sodium delivery to the distal nephron because if your blood pressure has dropped, you get reduced infiltration.
And then reduced sodium delivery at the distal nephron
This causes juxtaglomerular apparatus to release renin
Renin then catalyses the conversion of angiotensinogen to angiotensin I that’s then converted to angiotensin 2 by angiotensin converting enzyme in the lungs.
Angiotensin 2 is an active peptide which activates type 1 AT receptors causing vasoconstriction
Also acts on adrenal gland to drive the synthesis of aldosterone
Aldosterone causes renal salt water retention

Aortic arch baroreceptors tell you your pressures dropped because of drop in pressure in heart
They then activate the sympathetic nervous system
This activates the heart via beta-receptors by circulating adrenaline which increases heart rate
Also affects vascular tone through alpha-receptors- this causes vasoconstriction

Atrial stretch receptors in heart tell you about the amount of volume that’s being returned to the heart
This causes a reduction in the synthesis of atrial peptides

Question 16

Actions of aldosterone

Answer 16

Na/K/ATPase in the epithelial
creates electrochemical gradient - creates net positivity on blood side

Na+ H+ K+ antiporter in the intercalated cell
Creates a high carbon hydrogenated ions by carbonic anhydrase as there is in the proximal tubule

With this electrochemical gradient created, you can reabsorb bicarbonate and potassium

The importance of what happens here is that what
you are getting sodium reabsorption driven here and you will then excrete either hydrogen ions or potassium in exchange for it, depending on how active your hydrogen potassium antiporter is

Alodestrerone system of nephron means that when you activate it with aldosterone, it clings onto sodium and it exchanges that for either potassium or acid, one or the other.

if you activate it as you do when you’ve got a problem at the loop of Hendler level, so you’ve got wasting of sodium,
then what you end up with is a high Alkalosis.
you’re wasting potassium and acid because you’re trying to
hang on to sodium.

if it’s underactive, what you can end up with is hyperkalemia and or acidosis and the inadequate kind
of retention of sodium

Question 17

Actions of aldosterone

Answer 17

Steroid hormone- predominantly acts on transcription

Increase expression of ENaC (epithelium sodium channels), Na/K, ATPase pumps

More Na+ is reabsorbed and more K+ is secreted

H2O and Na is retained leading to BP raised as more blood volume (helps maintain BP)

Mineralocorticoid receptor also activated by cortisol

Cortisol entry to renal tubular cells prevented by 11-beta hydroxysteroid dehydrogenase

Excessive aldosterone activity produces sodium retention, hypertension and hypoakalaemic alkalosis