What is the plasma clearance?
The volume of plasma completely cleared of a particular substance per minute
How can the plasma clearance of a substance be calculated?
Clearance of substance X = rate of excretion of X/plasma concentration of X
What is the clearance of inulin and what implications does this have clinically?
Inulin clearance = GFR
Therefore, inulin clearance can be used to calculate GFR
What is the plasma clearance of glucose and why?
Clearance = 0
It is filtered in the glomerulus, completely reabsorped and not secreted from plasma or excreted in urine
What will the clearance of a substance that is filtered, partly reabsorped and not secreted be and give an example?
Clearance < GFR
What will the clearance of a substance that is filtered, secreted and not reabsorped be, and give an example?
Clearance > GFR
What is para-amino hippuric acid?
An exogenous organic anion used clinically to calculate renal plasma flow
What is the clearance of para-amino hippuric acid?
Complete - it is filterd, secreted, but not reabsorped
All the PAH in the plasma that escapes filtration is secreted from the peritubular capillaries
What is the filtration fraction?
The fraction of plasma flowing through the glomeruli that is filtered into the tubules
i.e. ~20% of the plasma that enters the glomeruli is filtered - the remaining 80% moves on to the peritubular capillaries
Which substances are reabsorped in the proximal tubule?
Which substances are secreted in the proximal tubule?
What are the five steps in tubular reabsorption?
1. Absorption into epithelial cell
2. Movement across epithelial cell
3. Transport out of epithelial cell
4. Diffusion across interstitial fluid
5. Diffusion across capillary wall
What does paracellular transport in the proximal tubule depend on?
Tightness of junction between tubular epithelial cells
Which kind of transport mechanism is essential at th basolateral membrane for sodium reabsorption, and how does this occur?
The energy-dependent Na+-K+ ATPase transport mechanism at the basolateral membrane pumps sodium out of the epithelial cell, creating a concentration gradiant that draws sodium out of the proximal tubule by diffusion
Sodium pumped into interstitial fluid is then taken into blood by diffusion
How can the concentration gradient of sodium from proximal tubule to epithelial cell, created by the active transport pump at the basolateral membrane, be used for reabsorption of other substances?
The sodium gradient can be used to drive glucose and amino acid uptake, using secondary active transport and co-transporters
It can also be used to secrete H+ into the filtrate
What percentage of the filtered glucose is reabsorbed in the proximal tubule?
What is the definition of the transport maximum e.g. of glucose?
The greatest quantity of glucose filtered from the plasma that can successfully be reabsorped in the proximal tubule
Explain why the blue line for 'excreted' only occurs later in the graph?
Glucose only begins to be excreted once the transport maximum has been reached
Excretion is the difference between filtration and reabsorption
What percentage of salt and water is reabsorbed in the proximal tubule?
How is Cl- reabsorption in the proximal tubule driven?
Driven by the paracellular pathway to Na+ reabsorption
What is the function of the loop of henle?
To create a cortico-medullary solute concentration gradient
What is reabsorped in the ascending limb of the loop of henle?
Is the ascending limb of the loop of henle permeable or impermeable to water?
Is the reabsorption of salt active or passive in the ascending limb of the loop of henle?
Active in the upper/thick part
Passive in the lower/narrow part
What is reabsorped in the descending limb of the loop of henle?
It does not reabsorb salt
Through which transport mechanism is salt reabsorped in the thick ascending limb of the loop of henle?
Na+ K+ Cl- triple co-transporter
How is potassium from the triple co-transporter in the thick ascending limb of the loop of henle used in salt reabsorption?
It is recycled: a cotransporter uses potassium to pump Cl- into the interstitial fluid and then the K+ is used in a countertransporter to pump Na+ from the cell
What is the purpose of countercurrent multiplication?
To concentrate the medullary interstitial fluid, enabling the kidney to respond to ADH to produce urine of different volume and concentration
What effect does ADH have on the collecting duct?
ADH changes the permeability of the collecting duct from water impermeable to water permeable, to allow reabsorption
What is vasa recta?
A group of straight capillaries in the medulla that lie alongside the loop of henle and act as a countercurrent exchanger
How does the vasa recta ensure NaCl and urea aren't washed away by essential medullary blood flow, as illustrated in this diagram?
Vasa recta capillaries follow hairpin loops and are freely permeable to NaCl and water
Blood flow to vasa recta is low
Which two receptors control ADH release?
Atrial stretch receptors
What is ADH release stimulated by?
Increased osmolarity (detected by hypothalamic osmoreceptors)
Decreased blood pressure/fluid volume (detected by atrial stretch receptors)
Does nicotine inhibit or stimulate ADH release?
Does alcohol inhibit or stimulate ADH release?
How does salt imbalance manifest in the body?
As changes in extracellular volume
When is aldosterone secreted?
In response to the RAAS
In response to rising K+ or falling Na+ in the blood
What does aldosterone do?
Stimulates Na+ reabsorption and K+ secretion
What effect does a change in body pH have on the nervous system?
Acidosis can lead to depression of the CNS
Alkalosis can lead to overexcitability of the peripheral NS and later the CNS
From what three sources is H+ continually added to the body from?
Carbonic acid formation
Inorganic acids produced during breakdown of nutrients
Organic acids resulting from metabolism
What is pKa?
The pH at which an acid is 50% dissociated
What is the normal plasma pH?
What is the most important physiological buffer system?
The CO2-HCO3 buffer system
How is bicarobonate reabsorbed in the proximal tubule?
CO2 and H2O are taken into the epithelial cell and carbonic anhydrase converts these into carbonic acid, H2CO3
This then dissociates into H+ and bicarbonate, HCO3
Bicarbonate is then taken into the extracellular fluid by co-transportation out of the epithelial cell with Na+
What happens to H+ ions that have dissociated from carbonic acid in the epithelial cell?
It can be transported actively back into the tubule and can either combine with phosphate to be excreted or may be recycled and taken back into the epithelial cell
How is 'new' bicarbonate generated in the kidney?
In the epithelial cell, carbonic acid dissociated into H+ and bicarbonate
The H+ is pumped actively into the tubule and binds with phosphate to form an acid, which is then excreted
It can also bind to NH3 in the filtrate to form ammonia which is then excreted
The corresponding bicarbonate is then reabsorped, and there is a net gain of bicarbonate
What is titratable acid and how is it measured?
The amount of H+ excreted as (largely) H2PO4-
Measured as the amount of strong base needed to titrate the solution back to pH 7.4
What is the maximum amount of titratable acid the kidneys can produce daily?
What is the normal bicarbonate concentration in plasma?
Close to 25mmol
What is the normal arterial pCO2?
What is the difference between compensation and correction?
Compensation is the fixing of pH irrespective of what happens to pCO2 and [HCO3-]
Correction restores pH, pCO2 and [HCO3-] to normal
How does CO2 retention generate acidosis?
Increased [CO2] increases [H+] as the equilibrium of the CO2-HCO3 buffer system is shifted to the right
This also increases [HCO3] but pH is only a measure of [H+] concentration so only this is reflected
When is uncompensated respiratory acidosis indicated?
pH < 7.35 and PCO2 > 45 mmHg
Where would respiratory acidosis lie on a Davenport diagram?
Low pH, high [HCO3-]
How is respiratory acidosis compensated for?
Virtually no cellular buffering
High pCO2 stimulates H+ secretion into the filtrate
This generates 'new' HCO3 and plasma [HCO3] concentration rises
How does compensated respiratory acidosis look on a Davenport diagram?
What are some of the causes for respiratory alkalosis?
Low inspired PO2 at altitude (hypoxia stimulates peripheral chemoreceptors, hyperventilation lowers PCO2)
Hyperventilation (causes include fever, brainstem damage)
How does excessive removal of CO2 due to ventilation disorders cause alkalosis?
When is uncompensated respiratory alkalosis indicated?
pH > 7.45 and PCO2 < 35 mmHg
What does uncompensated respiratory alkalosis look like on a Davenport diagram?
How is respiratory alkalosis compensated for?
Reduced pCO2 reduces secretion of H+ from the kidney
This reduces the reabsorption of HCO3- and it is excreted in the urine, making the urine slightly alkaline
Plasma [HCO3-] is lowered
What does compensated respiratory alkalosis look like on a davenport diagram?
What are [H+] and [HCO3-] in metabolic acidosis and why?
Raised [H+] = lowered pH
Depleted [HCO3] due to excess buffering of H+, or due to loss from the body e.g. diarrhoea
How is metabolic acidosis indicated?
pH < 7.35 and [HCO3-]p is low
What does uncompensated metabolic acidosis look like on a davenport diagram?
How is metabolic acidosis compensated for?
Excess CO2 is blown off, shifting equilibrium to the right and decreasing [H+] and [HCO3-]
Because [HCO3-] is very low, filtered HCO3- is also low and very readily reabsorbed
This stimulates H+ secretion into the tubule to
1) allow more excretion of acid in the urine in the form of NH4 and titratable acid
2) generate 'new' bicarbonate
What does compensated metabolic acidosis look like on a davenport diagram?
How is metabolic alkalosis indicated?
pH > 7.45 and [HCO3-]p is high
What does metabolic alkalosis look like on a davenport diagram?
How is metabolic alkalosis compensated for?
Retention of CO2 shifts equilibrium to the right
[H+] and [HCO3-} increases
Filtered HCO3- load is so large compared to normal that not all of the filtered HCO3- is reabsorbed, so much of the HCO3- is excreted in the urine
What does compensated metabolic alkalosis look like on a davenport diagram?