US Lecture 4 - Tubular function Flashcards
What is the function of the kidney?
Central regulator of homeostasis - consume more salt and water than needed so we need to lose this and other waste products
What is osmolarity?
Measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane - each ion is counted seperately
Fill in the blanks of the kidney nephron during filtration
What does the renal tubular wall look like diagramatically?
Through which pathways does reabsorption and secretion take place?
Paracellular and transcellular from/to peritubular capillary to/from tubular fluid
What are the types of transport that can occur in the tubules?
Osmosis, Active transport, Co-transport, movement down electrical gradient and passive transport
What are the 2 types of passive protein transport?
Protein INdependent (lipophilic molecules) and dependent (hydrophilic molecules) transport
How do the graphs of conc vs time appear with protein IN/dependent transport?
How does active movement occur?
Directly coupled to ATP hydrolysis or in directly coupled
What is the graph of conc vs rate with active movement?
How does water transport occur?
By osmosis - through tight junctions or aquaporins
How is a passive uptake system regulated?
By reducing the number of channel proteins in the membrane, so the molecule only has one output, leading to regulation
How are proteins reabsorbed?
Protein attaches to membrane receptor, which is then endocytosed, and the protein and membrane receptor break apart
How does transport maxima vary?
Depending on circumstances and applies to whole individual
What does secretion do in the nephron?
Moves substances from peritubular capillaries into tubular lumen - constitutes of a pathway into the tubule, either by diffusion/transcellular mediated transport Active secretion from blood side into tubular cell and then into lumen
What are the most important substances secreted?
H+ and K+ Choline, creatinine, penicillin and other drugs are also secreted NB: creatinine secretion levels are so low that they aren’t very relevant, hence can be used as clearance
How uniform is reabsorption at the proximal convoluted tubule, distal convoluted tubule, collecting duct and loop of henle?
What is the structure of each of the cells lining the PCT, LoH, DCT and collecting duct?
What substances are reabsorbed in the proximal convoluted tubule?
What do the Na/K pumps in the basolateral membrane of PCT do?
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)
What does Na help to occur in reabsorption in the early proximal tubule?
Na+ entry down a large electrochemical gradient can bring about the “uphill” entry of glucose and a-a’s and exit of H+
What is the function of carbonic anhydrase in the early proximal tubule?
Leads to Na reabsorption and increased urinary activity
What is passively and actively reabsorbed in the PCT?
Passive: urea and water Active: Glucose, a.a., Na, K, Ca, Vit C, Uric acid Reabsorption of all solutes/water is sensitive to metabolic poisons
Is there any secretion in the proximal tubule and why is this important?
Net secretion of some substances from plasma into proximal tubular fluid, important because some drugs and other substances are excreted in this way and some drugs enter the tubular fluid and act further down the nephron
What is reabsorbed in the descending limb of loop of henle?
Water passively reabsorbed through squamous epithelium Na and K drawn in
What is reabsorbed in the ascending limb of loop of henle?
Cl actively reabsorbed, Na passively reabsorbed with it Bicarbonate reabsorbed Impermeable to water - cuboidal epithelium, few microvilli - high energy requirement so prominent mitochondria
What osmolarity is the tubular fluid leaving the loop of Henle?
Hypo-osmolar with respect to plasma
How are the substances reabsorbed in the loop of henle?
What can loop diuretics do?
Block the Na/K/Cl co-transporter in the ascending loop of Henle
What is the proximal part of the DCT’s structure?
Cuboidal epithelium, with few microvilli Complex lateral membrane interdigitations with Na pumps Numerous large mitochondria
What is reabsorbed in the proximal part of the DCT?
Na and Cl co-transporter linked to Ca reabsorption - higher amount of calcium being reabsorbed Na and chloride are reabsorbed by channel sensitive to thiazides
What is a specialisation that occurs at the macula densa?
Detects changes in [Na+] of filtrate
What happens at the distal part of DCT and the collecting duct?
DCT and CD - Na reabsorbed (dependent on aldosterone) CD - Adjustment of Na/K/H/NH4 Water reabsorbed under control of ADH Distal part of nephron is impermeable to water without ADH
How does reabsorption work in the distal DCT and CD?
Prinicpal cell - important in Na, K and H2O balance (Na/K ATP pump) Intercalated cell - important in acid-base balance (H-ATP pump)
What is an adaption of the cells in the cortical CD to regulate water transport?
Very ‘tight’ epithelium, so little paracellular transport Can regulate by changing number of aquaporin channels
Which single gene defects affect tubular function?
Renal tubule acidosis Bartter syndrome Fanconi syndrome
What is renal tubular acidosis?
Hyperchloremic metabolic acidosis, leads to impaired growth and hypokalaemia (can cause temporary paralysis)
Which mechanisms underlie the main types of defects in Bartter’s syndrome?
What is Bartter syndrome?
Excessive electrolyte secretion - antenatal BS leads to premature birth, polyhydramnios, severe salt loss, moderate metabolic alkalosis, hypokalaemia, renin and aldosterone hypersecretion
Which mechanisms underlie the main types of defects in Renal Tubular Acidosis?
Leak of protons back into the blood, so cannot reabsorbed the bicarbonate, leading to metabolic acidosis
What is Fanconi syndrome?
Increased excretion of uric acid, glucose, phosphate, bicarbonate, increased excretion of low MW protiens, disease of PCT associated with renal tubular acidosis
Which mechanisms underlie the main types of defects in Fanconi syndrome?
Lose transporters, so pump protons into the endosome, so one Na leaves and 2 Cl are brought in, so suppresses the transport maxima
What is normal plasma and urine osmolarity?
Plasma: 285-295 mosmol/L Urine: 50-1200 mosmol/L
Which of transcellular and Paracellular are more easily regulated?
Transcellular
What is transport maxima?
The highest amount of the substance they can absorb
What is a good example of transport maxima?
Glucose: when too much glucose is in the filtrate, then reabsorption occurs, but if there is too much glucose, their is a limit to reabsorption (transport maxima) so the rest is excreted
