Lecture 3: Glomerular and tubular function 1 Flashcards
What occurs in the capillaries of the glomerulus?
- 20% of plasma volume is filtered (about 125ml/min for both kidneys)
- GHP about 60mmHg, capsular oncotic pressure about 32mmHg, Caspsular hydrostatic pressure about 18mmHg
- It is located between 2 arterioles
How does GFR alter with blood pressure?
- As mean arterial pressure varies within relastic normals GFR stays constant due to renal Autoregulation
- At very low MABP (<80) it begins to decline and at very high MABP (>160) it begins to increase
How does GFR alter with constriction and dilation of afferent and efferent arterioles?
- Increase GFR
- Constriction of efferent
- Dilation of Afferent
- Decreased GFR
- Constriction of afferent
- Not sure there is a way to dilate the efferent
What are the mechanisms of renal autoregulation?
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Extrinsic methods:
- Renin-angiotensin II: Constriction of efferent arteriole (inc. GFR)
- ANP and BNP: Dilation of afferent arteriole (inc. GFR)
- Sympathetic nervous system: Constriction of afferent (dec. GFR)
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Intrinsic methods:
- Myogenic: Increasing arterial pressure stretches the afferent arteriole inducing it to constrict which offsets pressure increase and keeps GFR stable
- Tubuloglomerular feedback: Macula densa cells detect NaCl levels in DCT, if high they signal to afferent to constrict
How does the tubuloglomerular feedback mechanism work?
- High GFR –> more NaCl passes macula densa cells –> paracrine signals –> afferent arteriole contriction –> decreased GFR
How does the RAAS work?
- Low GFR –> less NaCl passes macula densa cells –> paracrine signals released –> JG cells release Renin which converts Angiotensinogen (from liver) –> Angiotensin I which –> angiotensin II (by ACE):
- –> constriction of efferent arteriole
- –> Increased aldosterone –> increased Na+ uptake from distal nephron –> increased BV
Overall what happens in the proximal tubule?
- Major site of filtarte reabsorption:
- 66% of water and inorganic ions reabsorbed
- 100% of glucose and A.A’s absorbed
- 90% of bicarbonate reabsorbed
- pH drops to 6.7 from 7.4
Describe the process of active transport in the early proximal tubule
- Na/K pump on basal membrane pumps out Na+, which down its conc. gradient diffuses into the peritubular capillaries
- On the apical surface (lumenal surface) Na+ diffuses down its concentration gradient as it is in high concentration in the lumen, but low conc in the cell due to the Na/K pump.
- As Na+ moves into the cell it co-transports other solutes in such as glucose
- These diffuse down their gradients out of the basal surface and into the blood
- Water follows the Na+ paracellularly via osmosis through leaky tight junctions
- Some solvents follow via this pathway which is solvent drag
How does bicarbonate reabsorption occur in the proximal tubule?
- HCO3- cant diffuse accross the apical membrane hence:
- HCO3- + H+ ⇔ H2CO3 ⇔ (conversion done by carbonic anhydrase) H20 + CO2
- CO2 can diffuse in freely, where in the cell it is converted back into H2CO3 and then into HCO3- which diffuses into the blood, and H+ which is pumped back into the lumen in exchange for a Na+ (NHE)
- 90% of filtered HCO3- is reabsorbed
How does the proximal tubule generate new bicarbonate?
How will an increase in ECF [H+] effect this?
- Metabolises glutamine to ammonium ion and bicarbonate
- Ammonium is secreted into the lumen by a Na+/NH4+ exchanger
- Bicarbonate is transported into the blood
- Increase in ECF [H+] –> increased glutamine metabolism
Why cant H+ be secreted into the lumen to maintain pH?
- All H+ excreted by NHE used to make bicarbonate
What is fanconi syndrome?
- Impaired ability for PCT to reabsorb HCO3-, Pi, amino acids, glucose, and low-MW proteins resulting in increased urinary excretion
What occurs in the late proximal tubule?
- Chloride becomes concentrated in lumen –> paracellular movement –> blood
- This causes lumen to become electropositive which induces Na+ to move paracellularly into blood
What is secreted in the proximal tubule?
- Organic anions and organic cations
- Anions move out through antiporter in exchange for Cl-, urate or OH-
- Cations move out through antiporter with H+