Last updated on December 17, 2018 at 18:43
The tubules work hard
Despite there being 180 L of ultrafiltrate produced each day is the urine output only 1 – 1.5 L/day, indicating that the tubules must do a lot of reabsorption. The urine also has a very different composition from the ultrafiltrate. When the tubules dysfunction will both the quantity and the quality of the urine be different.
This is a good time to introduce some new (or not) terms. Specific gravity is a measure of how concentrated the urine is compared to pure water. It’s calculated like this:
From this formula can we understand that if the concentration of your urine is the same as the concentration of pure water would the specific gravity be 1. However, because there are always some molecules or ion in urine (urine cannot be pure water) will the concentration of urine always be higher than the concentration of water, so the number will always be above 1. If your urine was just pure water would the specific gravity be 1.000. As we said, that’s impossible. The absolute lowest specific gravity of urine possible is 1.001, meaning that the urine is just barely more concentrated than pure water (just 0.1% more concentrated than water).
The normal value for specific gravity of urine is 1.010 – 1.012 if a person is well hydrated, but in pathological conditions or overhydration can it be as low as 1.001 (but never lower!). In exsiccosis can the specific gravity be around 1.030 – 1.035. There is no upper roof for specific gravity, as it can be above 1.035 in e.g. diabetes mellitus.
Hyposthenuria is the condition where the specific gravity is low, but we will get back to that later.
Primary tubular dysfunctions
We have both congenital and acquired primary tubulopathies. They are primary in the sense that there is no other renal damage in the background (at least in the early phase).
Renal tubular acidosis (RTA) is a condition where the tubules can’t excrete H+, so the kidney can’t acidify the urine, causing acidosis. It can have both congenital and acquired causes. There are three (important) types.
- RTA type 1 where the H+ excretion in the distal tubules is defective
- RTA type 2 where the bicarbonate reabsorption in the proximal tubules is decreased
- RTA type 4 where there is hypoaldosteronism or tubular cells are resistant to aldosterone. Hyperkalaemia also occurs.
See topic 76 for more details on RTA I and II.
It’s still uncertain if what was originally considered RTA type 3 actually exists, which is why the types are so weird. We’ll come back to this in the acidosis topics.
Renal diabetes insipidus can also be either congenital or acquired. It occurs when the distal and collecting tubule cells are AVP resistant, making them unable to concentrate the urine. A lot of water is lost in the urine.
Tubular hypoxia, whether due to hypoxaemia, ischaemia or transplant rejection will cause non-specific tubular damage with hyposthenuric polyuria.
Some toxins and drugs can cause tubulointerstitial nephritis, like mushroom toxins, antifreeze, drug effects and hypersensitivity reactions. SNGFR will increase in the unaffected nephrons, damaging them as well.
Certain metabolic disorders, like uric acid, oxalate, hypokalaemia and hypercalcaemia can damage the tubules. Hypercalcaemia can cause metastatic calcification of the tubules, and can occur from paraneoplastic syndromes.
Autoimmune diseases like SLE or Sjögren syndrome can damage the tubules.
Fibrosis can compress and damage the tubules.
Renal glucosuria is a congenital condition where the person has limited ability to reabsorb glucose in the proximal tubule. This may cause osmotic diuresis.
Renal aminoaciduria is another congenital condition where the amino acid reabsorption capacity is reduced. It usually causes cysteine stones and amino acid deficiencies.
Renal phosphaturia may develop if there is hyperparathyroidism or if the tubules are too sensitive to PTH. This may cause rickets (bone weakness).
Fanconi syndrome is a congenital or acquired disorder characterised by glucosuria, aminoaciduria, phosphaturia and bicarbonate loss.
Secondary tubular dysfunctions
The glomerular filtration rate (GFR) counts the sum of SNGFR for all functional tubules in both kidneys. It’s therefore a measure of the total kidney filtration.
These dysfunctions occur because of a primary problem with filtration, which causes the tubules to have to adapt and compensate for the filtration problem.
If SNGFR is low (due to slight hypovolaemia or decreased RBF) will the filtrate flow slower through the tubules, allowing them more time to reabsorb, which causes more fluid to be reabsorbed into the plasma and less urine to be produced. This normalizes the plasma volume.
In cases where the number of functioning nephrons decreases must SNGFR of the remaining nephrons increase. Fewer nephrons but increased filtration through the remaining nephrons means that the total filtering capacity of the kidney isn’t reduced too much. However the SNGFR can’t increase infinitely so as more nephrons are lost will GFR eventually drop as well.
If no adaptation was done by the tubules would a lot of salt and water be lost by this extra filtration, so the tubules must also be increase the reabsorption of certain salts and water to avoid losing them. However, not all of the excess filtrate must be reabsorbed (if it were would it be meaningless to increase the SNGFR as all the extra filtrate would be reabsorbed), so only some of the excess filtrate must be reabsorbed.
So the tubules must adapt their reabsorption and secretion when the SNGFR is increased so that they don’t reabsorb too much. If they reabsorbed too much would the plasma concentration increase, which is bad. They must therefore “tone down” the reabsorption. However, the tubules adapt to this differently for different substances, and not at all for certain substances.
Na+ and K+ are very well adapted, meaning that the tubules excretes more of them as the SNGFR increases. This keeps the Na+ and K+ levels in the plasma stable. The kidneys produce natriuretic substances and aldosterone to increase the excretion of these two when the SNGFR increases.
H+ and phosphate are less regulated. When GFR decreases will PTH be produced, which increases excretion of phosphate.
Urea and creatinine are not regulated at all. There is no way for tubules to secrete urea and creatinine, so when filtration drops will urea and creatinine accumulate in the blood.
This graph shows the plasma concentration of different substances in correlation with the GFR. From this figure we can understand that hypernatraemia and hyperkalaemia only occurs when GFR is almost zero, while azotaemia (urea and creatinine in blood) occurs already when GFR drops to half its normal value.
Magnification is an important phenomenon in cases where the GFR is decreased, and it’s related to this tubular adaptation. The phenomenon states that the salt excretion will always be proportional to the reduction in GFR, so that if the GFR is 10x lower than normal will the Na+ excretion be 10x higher than normal, so as to maintain the correct plasma Na+ concentration. It’s basically the same as tubular adaption, I can’t see the difference.
63. Pathophysiology of glomerular filtration