4. Tubular Function Flashcards
What is osmolarity?
- A measure of solute concentration in a solution
- A measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane
- Dependent on the number of solute particles (not the nature)
What is the normal plasma and urine osmolarity?
• Plasma - 285-295mosmol/L
• Urine - 50-1200mosmol/L
- huge variation
- intake of different solutes from external environment varies considerably
- necessary to maintain a constant plasma osmolarity
Outline transport across the renal tubular wall
- Single epithelial layer
- Tight junctions at apical membrane
- Lateral intercellular spaces between cells at basolateral membranes
- Peritubular capillary in close association with basal membrane
- Movement may be in either direction (reabsorption or secretion) and can be transcellular or paracellular
- Active
- Passive - osmosis, co-transport, counter transport (antiporters) etc.
How does the passive movement of lipophilic molecules compare to hydrophilic molecules?
- Lipophilic - protein independent, directly proportional to solute concentration
- Hydrophilic - protein dependent, rate has a maximum (due to transport maxima of protein carriers)
What are the 2 types of active movement across a cell?
1) Directly coupled to ATP hydrolysis - substance moved into cell using energy from ATP hydrolysis (apical)
2) Indirectly coupled to ATP hydrolysis - substance moves out of the cell using the energy from ATP hydrolysis (basal), creating a concentration causing passive movement in at the apical membrane
How is glycosuria related to transport across a cell?
- Transport system for reabsorption of glucose is overloaded
- Not all glucose is reabsorbed from tubular fluid
- Some is excreted in the urine
What important substances are secreted from the peritubular capillaries into the tubular fluiid?
(passive or active) • H+ • K+ • Choline • Creatinine • Penicillin and other drugs
What proportion of glucose, amino acids, bicarbonate and sodium is reabsorbed in the PCT?
- 100% glucose, amino acids (+ nutrients)
- 90% bicarbonate
- 65% sodium
What is secreted and what is not reabsorbed from the PCT?
- H+ secreted
* Creatinine, sulphates, phosphates and nutrients are not reabsorbed
How are proteins reabsorbed?
- Protein binds to protein-receptors on the apical membrane
- Formation of a put
- Internalisation of protein-receptor complex into a vesicle
- Receptor dissociates + recycled
- Proteins broken down into amino acids and transported into the blood
Which component drives the majority of the reabsorption in the PCT and describe how different substances use this mechanism?
- Na/K pump on basolateral membrane
- Pumps Na+ out of cell into peritubular capillary
- Concentration and electrochemical gradient favours Na+ movement into the cell (indirect absorption)
- Couples the uphill movement of glucose and amino acids into the cell (symporter) and H+ out of the cell (antiporter)
- Urea and water follows passively
How does the structure of the descending limb compare to the ascending limb?
- Descending limb - thinner, highly permeable to water, fewer mitochondria
- Ascending limb - thicker, impermeable to water, more mitochondria
Describe the microstructure of the ascending limb
• Cuboidal epithelium with few microvilli
• Na/K pump on basal membrane creates gradient
- drives the symporter on apical membrane
- 1 Na+, 1 K+ and 2 Cl- ions into the cell
- inside of the cell becomes more negative (due to other movements of the ions)
• K+ channel on apical membrane allows it to leak back into the lumen
- this exaggerates the electrical gradient, driving the paracellular movement of Na+, K+, Ca2+ and Mg2+
What do loop diuretics do?
Block the Na/K/Cl co-transporter (lumen=>cell)
What proportion of water and Na & K is reabsorbed in the Loop of Henle?
- 85% of water
* 90% of Na+ % K+
Describe the movement of substances into the DCT cell
- Cuboidal epithelium with few mitochondria
- Na+ dependent uptake of Cl- occurs (co-transporter)
- Ca2+ enters cell by gradient
What do thiazides do?
- Target Ca2+ channels in DCT cell
* Knock on effect on plasma calcium
What is special about the part of the DCT where it meets the glomerulus?
- Macula densa
- Forms part of the juxtaglomerular apparatus
- Detects changes in [Na+] of the tubular fluid filtrate
Describe the distal DCT and cortical collecting duct
• Fine tuning of filtrate
• Principle cells:
- important in sodium, potassium and water balance
- in DCT, apical sodium channels are sensitive to aldosterone, and linked to K+ channel
- cortical collecting duct: controlled by vasopressin, tight epithelium - tightly regulate water
• Intercalated cells:
- exist between each principle cell
- important in acid-base balance
- mediated by a H+-ATP pump on the apical membrane
What are the 3 single gene defects which affect tubular function?
- Renal tubule acidosis
- Bartter syndrome
- Fanconi syndrome
What is renal tubule acidosis?
• Inability to acidify urine below pH5.5
• Leads to hypercholermic metabolic acidosis of the blood
• Symptoms also include impaired growth and hypokalaemia
• Defect in the distal renal tubule => failure of H+ secretion (usually swapped in with HCO3-)
• Can be caused by:
- malfunction of bicarbonate transport out of tubular cell into blood, accumulation, limited carbonic anhydrase activity
- mutation in carbonic anhydrase enzyme
What is Bartter Syndrome?
- Excessive electrolyte secretion
- Mutation in Na/Cl/K co-transporter on ascending limb or mutation in the K+ channel
- Causes evere salt loss, moderate metabolic alkalosis, hypokalaemia, renin & aldosterone hypersecretion
- Antenatal Bartter syndrome = more severe, premature birth, polyhydramnios
What is Fanconi Syndrome?
• Failure of protein reabsorption
• Increased excretion of low molecular weight proteins
• Increased excretion of uric acid and glucose phosphate
• Caused by defect in Cl- channel involved in protein-receptor vesicle recycling
- reduction in protein receptors
• Consequences include excessive amount of cytokines flowing through tubular system => immune response
