L5: tubular function 1 - PCT Flashcards

1
Q

What is reabsorption?

A
  • selective process
  • reabsorption because it has already once been absorbed in the gut
  • solutes and water needed by the body (most are valuable) are removed from the PCT filtrate and out back into peri-tubular capillaries
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2
Q

What is secretion?

A
  • second chance to actively eliminate unwanted substances from blood into urine (only 19-20% filtered)
  • moved from peri-tubular capillaries into PCT lumen
  • few substances are secreted - present in great excess (H+,K+), natural toxins (NH3, urea), drugs (penicillin, dopamine, indonethacin, food additives), substances bound to proteins
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3
Q

What does the PCT do?

A
  • most reabsorption occurs here (65-67%) takes place here - many substances are too valuable to risk losing by waiting to reabsorb later on
  • reabsorption of 2/3 of ions and water, and all glucose, amino acids and vitamins
    (Pic at 18:44 of PCT)
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4
Q

Histology of PCT

A

19:40 pic

Deeply stained cytoplasm of PCT due to high content of organelles such as mitochondria which provide energy required for reabsorption processes, PCT cells also have a brush border which increase absorptive capacity by increasing SA. DCT cells have an absence of the brushed border which gives cell appearance of a larger lumen than PCT. PCT is about a third of the length of the nephron.

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5
Q

How does filtrate move through the PCT?

A

Apical side = brush border; basolateral side = closer to interstitium
Filtrate has to move from tubule lumen to PCT cell to the interstitium into the peritubular capillary.

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6
Q

Transcellular and paracellular movement

A

Transcellular:

  • transport across special membrane
  • diffusion through tubular cell cytoplasm
  • transport across the basolateral membrane
  • movement through the interstitium to blood vessels

Paracellular:
- movement through leaky tight junctions

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7
Q

Movement from interstitium to peritubular capillaries

A

Once something is moved into the interstitium, it’s concentration is higher than in the peritubular capillaries and so it moves passively by diffusion into the blood vessel.

Peritubular capillaries are more porous than most capillaries and also have very low blood pressure, so are therefore good at allowing material to diffuse back into them.

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8
Q

How is the PCT efficient at reabsorbing?

A

There are millions of sodium potassium ATPases on the basolateral membrane of each PCT cell.
They use energy to establish an ionic gradient across the tubular cell membrane, with sodium being pumped out of the cell, lowering intracellular sodium.
This provides a driving force for the reabsorption of sodium from the filtrate into the tubular cell and then out into the blood.
Use entry of sodium to bring in other solutes which can be transported by a secondary active transport process along with the reabsorbed sodium (symport) e.g., glucose.

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9
Q

Why is energy needed to drive sodium reabsorption?

A

Sodium has the highest concentration making up a big proportion of plasma osmolality. This means if it is removed using energy, most possible water will follow by osmosis.

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10
Q

How is a sodium electrochemical gradient established?

A
  1. 3Na+ pumped out of the basal and basolateral side of the PCT cell by sodium potassium ATPases in exchange for 2K+. The high sodium concentration in the interstitium diffuses into the blood.
  2. Sodium enters the cell through open sodium channels, moving down its electrochemical gradient by diffusion and is pumped into the interstitium by the sodium potassium ATPase.
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11
Q

Sodium reabsorption coupled with glucose uptake

A
  1. Sodium is moved out by ATPase.
  2. Sodium moves down its EC gradient and pulls glucose into the cell using the SGLT1 and SGLT2 co-transporter channels.
  3. Glucose diffuses out of the basolateral side of the cells using the GLUT2 channel and sodium is pumped out by the ATPase.
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12
Q

Sodium reabsorption coupled with bicarbonate uptake

A
  1. Sodium moved down its EC gradient and is exchanged for H+ via a Na+/H+ anti-porter. Na+ is pumped out by the ATPase.
  2. Secreted H+ combined with filtered bicarbonate to give rise to CO2 and H2O., using carbonic anhydrase located on the apical brush border of PCT cells.
  3. CO2 diffuses into the tubular cell and recombines with water to give bicarbonate, which exits the cell from the basolateral side and diffuses into the blood. The H+ ion produced moves back out by the Na+/H+ antiporter.
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13
Q

How is water reabsorbed in the PCT

A

Lots of the osmolality has been picked up and sent into the blood. This means water moves out of the PCT into the blood by osmosis by a paracellular route and transcellular route (through aquaporin 1, AQP1).

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14
Q

Summary of sodium reabsorbed aiding reabsorption of water and many other solutes

A
  1. Sodium moves down its EC gradient due to the action of the ATPases.
  2. Many substances are co-transported with sodium, e.g., glucose, amino acids and bicarbonate
  3. Water is reabsorbed by osmosis by obligatory water movement. The concentration of remaining solutes in the PCT lumen increases in the filtrate so they now move down their chemical gradients by diffusion.
  4. Lipids move transcellularly
  5. Cl-, K+, move paracellularly
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15
Q

Fate of molecules as they pass down the PCT

A

Same sodium, same potassium, higher chloride, lower bicarbonate, very low glucose and amino acids, higher urea

All in relation to how much is pulled out comparatively to water.

Table at min 47

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16
Q

Is the PCT hypotonic, isotonic or hypertonic in relation to the plasma?

A

Isotonic
The plasma osmolality remains the same due to same amount of ions, just different composition. Filtrate is neither dilutes nor reabsorbed. So by the end of the PCT, filtrate remains isotonic with respect to plasma.

17
Q

What is clearance (of drugs)?

A

Clearance is the volume of blood cleared of drug per unit of time

18
Q

What is excretion (of drugs)?

A

Amount of drug excreted over a period of time

19
Q

What does clearance depend on?

A

Whether the drug is filtered, secreted or reabsorbed; GFR; structure of drug; age; disease

20
Q

Difference between a high and low clearance

A

High clearance = eliminated from the blood rapidly by the kidneys
Low clearance = inefficient excretion - only low levels to be administered to maintain their level in blood and prevent adverse drug reactions

21
Q

Why is knowing drug clearance rate important?

A

Important to know drug clearance rate so the right dosage is given to maintain a plasma concentration to achieve a therapeutic effect.

22
Q

Relationship between renal function, clearance and plasma half life

A

A decreases renal function will mean there is a decreased clearance of the drug and an increased plasma half life of the drug.