Basic tubular function Flashcards
what is the kidney?
The kidney is a central regulator of homeostasis
What components of urine do we not have a method of transporting on their own?
Urea and Water - so these move in by passive transport
What percentage of the ultrafiltrate is reabsorbed?
99%
Define osmolarity and how can you calculate it
The measure of osmotic pressure exerted by a solution across a semi-permeable membrane.
This is dependent on the number of particles in a solution and not the nature.
Osmolarity = All the concentrations of the different solutes (measured in mmol/l) added together. Each ion is “counted” separately
What is the range for normal plasma osmolarity? What makes up the majority of this?
285-295 mosmol/L
Mainly consists of sodium (140 mmol/L)
What is the range for normal urine osmolarity?
50-1200 mosmol/L
where does absorption take place?What are the two pathways through the urinary epithelium?
It occurs across the tubular wall.
Have an epithelial surface, has tight junction basolateral membrane and lumen.
Transcellular (through the cell) and Paracellular (through tight junctions)
How much paracellular is dependant on how tight the junctions are.
What is the difference between lipophilic passive transport and hydrophilic passive transport?
Lipophilic passive transport has a linear relationship with solute concentration.Protein independent transport (lipophilic molecules)
Hydrophilic passive transport is saturable because it is dependent on the availability of channel proteins.Protein dependent transport (hydrophilic molecules
Describe the relationship between solute concentration and rate in active movement ?
Directly coupled to ATP hydrolysis has the same curve as Indirectly coupled to ATP hydrolysis
As the solute concentration increases, the rate increases until a certain point where it plateaus.
How does water move?
- Water can move through tight junctions if it isn’t too tight
- It also moves through aquaporins
How is a passive system regulated?
The channel is inside the cell. When you want more of the molecule, the channel moves to the cell surface membrane (more of it does)
What are the two routes for water to pass through the renal tubular wall?
Transcellular and Paracellular
How can hydrophilic passive transport be upregulated or downregulated?
By changing the number of transporters available e.g. ADH increases the amount of Aquaporin 2 on the apical membrane
How does protein reabsorption normally happen?
Receptor mediated endocytosis - the protein binds to a receptor and is endocytosed
The acidity of the endosome allows the complex to dissociate and the receptors are recycled
What happens if the concentration of a solute in the urine exceeds the transport maxima and give an example?
It is excreted in the urine e.g. glucose which is an indication of diabetes mellitus, or intake of large amount of vit B and Vit C
Describe fully what happens inside the lumen of the nephron?
Once inside the lumen of the nephron, small molecules, such as ions, glucose and amino-acids, are reabsorbed from the filtrate
- Specialised proteins called transporters are located on the membranes of the various cells of the nephron.
- These transporters trap the molecules as they flow by them
- Each transporter traps only one or two types of molecule. For example glucose is reabsorbed by a transporter that also traps sodium.
- Water gets reabsorbed passively by osmosis in response to build up of Na in intercellular spaces.
- Some transporters require energy, usually in the form of ATP (active transport), while others do not (passive transport).
- Transporters are located in different parts of the nephron. Most of the Na transporters are located in the proximal tubule, while fewer are spread out through other segments.
What are the most important substances that are secreted?
H+
K+
where does secretion take place?
- Moves substances from peritubular capillaries into tubular lumen
- Like filtration, this constitutes a pathway into the tubule
- Can occur by diffusion or by transcellular mediated transport
- Active secretion from blood side into tubular cell (via basolateral membrane) and from cell into lumen (via luminal membrane)
Describe the differences in sodium reabsorption throughout the nephron.
65% reabsorbed in PCT
25% reabsorbed in ascending loop of Henle
8% reabsorbed in DCT
Variable absorption regulated by aldosterone and vasopressin in collecting duct, this is the only part that is regulated.
Where is most bicarbonate reabsorbed?
90% is reabsorbed in the PCT
Where, along the nephron, do you find cells that don’t have that many mitochondria?
Descending loop of Henle and collecting duct
These areas are mainly involved in the passive transport of water
Describe the features of a cell in the proximal convoluted tubule.
Numerous mitochondria
Brush border to increase surface area
Designed for lots of reabsorption
What is the most important protein of the cells lining the tubules throughout the nephron?
Na+/K+ ATPase - responsible for the sodium gradient that drives the movement of most substances.
Na/K pump keeps intracellular [Na] low and [K] high.
Large conc. and electrical gradients favour Na movement into the cell (occurs in most nephron segments)
Which substances move in or out with Na+ in the early proximal tubule?
H+ moves out (Na+/H+ countertransport)
Glucose in (Na+/glucose cotransport)
Amino acids in (Na+/amino acid cotransport)
Na+ entry down a large electrochemical gradient can bring about the “uphill” entry of glucose and a-a’s and exit of H+
How is proton excretion linked to bicarbonate reabsorption?
Protons are pumped into the tubule, out of the early proximal tubule via (Na+/H+ exchanger)
Protons react with HCO3- to form H2CO3
H2CO3 converted by carbonic anhydrase to CO2 + H2O
CO2 + H2O moves into the cell and carbonic anhydrase converts it back to H2CO3, which dissociates to form H+ and HCO3-.
HCO3- is passes into the blood, H+ moves out again via the Na+/H+ exchanger
What overall happens in proximal tubule and why is this important?
There is net secretion by the PCT.
Important because:
-it is a route of excretion for some substances
-some drugs enter the tubular fluid here and act further down the nephron.
Describe the loop of henle
Descending limb:
squamous epithelium with few mitochondria
Permeable to water
Water passively reabsorbed; Draws in Sodium and Potassium
Ascending limb:
Cuboidal epithelium, few microvilli but many mitochondria
Impermeable to water (due to very tight junctions and no aquaporins), Na+, K+ and Cl- reabsorbed here
Chloride actively reabsorbed
Sodium passively reabsorbed with it
Bicarbonate reabsorbed
By now 85% water and 90% sodium and potassium have been reabsorbed.
Tubular fluid leaving the loop of Henle is hypo-osmolar with respect to plasma
What channels are found in the cells lining the ascending loop of Henle?
Na+/K+/Cl- triple transporter
What type of diuretics blocks this channel?
Loop diuretics
Describe the epithelium of the distal convoluted tubule.
Cuboidal epithelium + few microvilli
There are lateral membrane interdigitations with Na+ pumps
Numerous large mitochondria
Which transporter is found on the apical membrane in cells in the DCT and how do we need this?
Na+/Cl- cotransporter
which is linked to ca2+ reabsorption.
If we block the Na+/Cl- cotransporter with the thiazide, you get an increase in the Ca2+.
This is because under normal conditions, you pump out Na+, so Na+ can enter passively through Na+/Cl- co-transporter or Na+/Ca2+. Thiazide blocks the Na+/Cl- co-transporter so Na+ can only enter via the Na+/Ca2+ co-transporter, which means cellular levels of ca2+ decreases and increases in the blood stream.
So increase in plasma calcium
What other substance is reabsorbed here?
Ca2+ - there is an Na+/Ca2+ exchanger on the basolateral membrane
What type of diuretic acts on this transporter and what are the consequences?
Thiazide diuretics - leads to increase in plasma calcium concentration
What does the macula densa cells do?
Detect Na+ concentration of the fluid in the tubule - can stimulate release of renin
What is the reabsorption of sodium in the distal part of the DCT and the collecting duct dependent on?
Aldosterone
What is needed for reabsorption of water in the collecting duct?
Vasopressin
What are the two types of cells in the collecting duct and how do their functions differ?
Principal cells - regulate movement of Na+/K+/water
Intercalated cells - regulate acid-base balance
State three single gene defects that affect tubular function.
Renal tubule acidosis Bartter syndrome Fanconi syndrome (Dent's disease)
What is renal tubule acidosis? State some clinical features.
Metabolic acidosis caused by failure of the renal tubules.
Hyperchloremia
Hypokalemia
Impaired growth.
- Protons are not excreted, so we get acidosis in the blood.
- can also occur with carbonic anhydrase which leads to production of hydrogen ions to be excreted out.
What is Bartter syndrome? State some clinical features.
Excessive electrolyte secretion
Antenatal barrter syndrome: Premature birth Polyhydramnios Severe salt loss, so water also moves out Moderate metabolic alkalosis hypokalemia renin and aldosterone hypersecretion
What causes Bartter syndrome?
Mutation in the Na+/K+/Cl- triple transporter
NOTE: at this point in the loop of Henle around 25% of sodium is reabsorbed
What is Fanconi syndrome (Dent’s disease) and what causes it?
Increased excretion of uric acid, glucose, phosphate, bicarbonate.
Increased excretion of low Molecular weight protein.
This can be due to Disease of the proximal tubules associated with Renal tubular acidosis (type 1)
OR dent’s disease, which is:
Failure in endosomal recirculation.
Caused by failure of the chloride transporter
Protein-Receptor complex dissociates due to the acidity of the endosome, which is caused by influx of H+ ions
H+ influx must be balanced by influx of Cl- to ensure a charge gradient isn’t established (which would make it more difficult to pump more H+ in)
Failure of the chloride channel means that the endosome pH never becomes low enough for the protein-receptor complex to dissociate.
Clinical features of Fanconi syndrome: Increased excretion of low molecular weight proteins, increased excretion of uric acid, glucose, phosphate and bicarbonate
