Tubular Function Flashcards
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.
The measure of osmotic pressure exerted by a solution across a semi-permeable membrane.
This is dependent on the number of particles not the nature.
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
What are the two pathways through the urinary epithelium?
Transcellular and Paracellular (through tight junctions)
What is the difference between lipophilic passive transport and hydrophilic passive transport?
Lipophilic passive transport has a linear relationship with solute concentration
Hydrophilic passive transport is saturable because it is dependent on the availability of channel proteins.
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?
It is excreted in the urine
What are the most important substances that are secreted?
H+
K+
Describe the differences in sodium reabsorption throughout the nephron.
65% reabsorbed in PCT
25% reabsorbed in ascending loop of Henle
8% reabsorbed in DCT
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
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)
How is proton excretion linked to bicarbonate reabsorption?
Protons are pumped into the 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
Describe the differences between the ascending and descending loop of Henle.
Descending loop of Henle - permeable to water - SQUAMOUS epithelium
Ascending loop of Henle - impermeable to water, Na+, K+ and Cl- reabsorbed here - CUBOIDAL epithelium
Water leaves the top of the loop of Henle being hypoosmolar
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?
Na+/Cl- cotransporter
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
What is Bartter syndrome? State some clinical features.
Excessive electrolyte secretion Hypokalemia Premature birth Polyhydramnios Renin and aldosterone hypersecretion Moderate metabolic alkalosis
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? Refer to endosomes.
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
