Which substances are reabsorbed by carrier mediated transport systems?
glucose, amino acids, organic acids, sulphate and phosphate ions.
What does Tm stand for?
Transport capacity - if Tm is exceeded then the excess substrate enters the urine
What is the renal threshold?
The plasma concentration at which saturation occurs
Describe the filtration capability of glucose
1.Glucose is freely filtered, so whatever its [plasma] that will be filtered.
2. In man for plasma glucose up to 10 mmoles/l, all will be reabsorbed.
Beyond this level of plasma [glucose], it appears in the urine = Renal plasma threshold for glucose.
(If plasma [glucose] = 15 mmoles/l, 15 will be filtered, 10 reabsorbed and 5 excreted.)
After 10 mmol/l of glucose - literally every other portion of glucose in the blood will be excreted in the urine
Does the kidney regulate blood glucose concentration?
No (insulin and the counter-regulatory hormones responsible for its regulation).
What does the presence of glucose in the urine suggest?
The appearance of glucose in the urine of diabetic patients = glycosuria, is due to failure of insulin, NOT, the kidney. N.B. Any patient with glucose in their urine should be followed up.
Describe the Tm (transport capacity) of amino acids
For amino acids, Tm is also set so high that urinary excretion does not occur, regulated by insulin and counter-regulatory hormones.
What substances does the kidney regulate by means of the transport capacity mechanism?
Some examples include:
sulphate and phosphate ions.
How does the kidney regulate levels of sulphate and phosphate levels?
This is because Tm is set at a level whereby the normal [plasma] causes saturation.
Any above the normal level will be excreted, therefore achieving its plasma regulation.
(Also subject to PTH regulation for phosphate, PTH ¯ reabsorption).
Where do most of the sodium ions get reabsorbed? How is it reabsorbed?
65-75% occurs in the proximal tubule
Not reabsorbed by a Tm mechanism, but by active transport, which establishes a gradient for Na+ across the tubule wall.
99.5% of sodium is reabsorbed in total
Which side of the tubule cell contains the sodium potassium pump?
The side which is exposed to the interstitial fluid - not the side which is exposed to the tubule lumen
Active Na+pumps are located on the basolateral surfaces, where there is a high density of mitochondria.
This decreases [Na+] in the epithelial cells, increasing the gradient for Na+ ions to move into the cells passively across the luminal membrane.
What aspect of the proximal tubule cells makes them effective at allowing sodium diffusion?
Na+ is not permeable at cell membranes!
The brush border of the proximal tubule cells has a higher permeability to Na+ ions than most other membranes in the body, partly because of the enormous surface area offered by the microvilli and the large number of Na+ ion channels, which facilitate this passive diffusion of Na+.
How does the reabsorption of sodium aid the reabsorption of other components of the filtrate?
Negative ions such as Cl- diffuse passively across the proximal tubular membrane down the electrical gradient established and maintained by the active transport of Na+.
The active transport of Na+ out of the tubule followed by Cl- creates an osmotic force, drawing H2O out of the tubules.
H2O removed by osmosis from the tubule fluid concentrates all the substances left in the tubule creating outgoing concentration gradients.
What determines the rate of reabsorption of non-actively reabsorbed solutes?
a) amount of H2O removed, which will determine the extent of the concentration gradient.
b) the permeability of the membrane to any particular solute.
Describe the permeability of the membrane to urea
Tubule membrane is only moderately permeable to urea, so that only about 50% is reabsorbed, the remainder stays in the tubule.
What substances os the tubular membrane impermeable to?
For some substances eg inulin and mannitol, the tubular membrane is impermeable.
How is the transport of sodium related to the transport of glucose?
Substances such as glucose, amino acids etc, share the same carrier molecule as Na+ (symport).
High [Na+] in the tubule facilitates and low [Na+] inhibits glucose transport.
What might disrupt renal function if the sodium transport requires ATP?
Decreased blood flow
What is the function of the SGLT protein?
SGLT = Sodium-dependent glucose transporter
Allows sodium to travel down the electrochemical gradient and pulls glucose into the cell against the concentration gradient
What else is sodium reabsorption linked to?
Na+ reabsorption also linked to HCO3- ion reabsorption (A/B).
What is another route into the tubule lumen?
Secretory mechanisms transport substances from the peritubular capillaries into the tubule lumen
What substances is tubular secretion important for?
Important for substances that are protein-bound, since filtration at glomerulus is very restricted. Also for potentially harmful substances, means can be eliminated more rapidly
What is the benefit of non-specific carrier mechanisms allowing secretion of organic acids?
Means the mechanisms that secrete lactic acid and uric acid can also be used for substances such as penicillin, aspirin, and PAH (para-ammino-hippuric acid)
What transport mechanism can be used to secrete morphine and atropine?
organic base mechanism for choline, creatinine
Where are these substances excreted?
At the proximal tubule
What is the major cation in cells?
Potassium - normal ECF [K+} is around 4mmoles/l
What is the consequence of hyperkalaemia (5.5 mmoles/l)
Decreased resting membrane potential of excitable cells and eventually ventricular fibrillation and death
What is the result of hypokalaemia?
Potassium less than 3.5 mmoles/l
Increases resting membrane potential (hyperpolarizes muscle, cardiac cells) - cardiac srrhythmias and eventually death
Where is potassium normally reabsorbed?
Potassium filtered at the glomerulus and is reabsorbed primarily at the proximal tubule
What brings about changes in potassium excretion?
Chenges in secretion in the distal parts of the tubule.
Any increase in renal tubule cell [K+] due to increased ingestion will stimulate K+ secretion, while any decrease in intracellular [K+] results in reduced secretion.
What hormone is responsible for regulating potassium balance?
Adrenal cortical hormone aldosterone
When does aldosterone get produced?
An in [K+] in ECF bathing the aldosterone secreting cells stimulates aldosterone release which circulates to the kidneys to stimulate in renal tubule cell K+ secretion.
What is the effect of aldosterone on sodium?
Aldosterone also stimulates Na+ reabsorption at the distal tubule but by a different reflex pathway.
H+secretion: H+ions are actively secreted from the tubule cells (not the peritubular capillaries) into the lumen A/B Balance.