Reabsorption/secretion in proximal tubule Flashcards

1
Q

How much of the glomerular filtrate is reabsorbed in the proximal tubule?

A

2/3rds

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2
Q

How is reabsorption in the proximal tubule conducted?

A

Iso-osmotically

- there is virtually no change in osmolarity of GF as it flows along the PT

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3
Q

Fact:
Role of PT is mass reabsorption of GF, while the regulation of transport of water and solutes occur in the DT. However, due to the volume of fluid absorbed in the PT, any change in the rate of reabsorption here can have significant impact on the volume of ECF. So, PT is also an important regulatory site in controlling ECFV

A

Fact:
role of PT is mass reabsorption of GF, while the regulation of transport of water and solutes occur in the DT. However, due to the volume of fluid absorbed in the PT, any change in the rate of reabsorption here can have significant impact on the volume of ECF. So, PT is also an important regulatory site in controlling ECFV

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4
Q

What are the major solutes that contribute to the iso-osmotic reabsorption from the PT?

A
  1. Sodiium
  2. chloride
  3. bicarbonate
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5
Q

How is sodium reabsorbed (main mech)?

A

By an active transport mechanism

  • Sodium reabsorption occurs throughout the tubule, although 65% of it is reabsorpbed in the PT.

(energy consuming process and accounts for majority of the oxygen consumed in the kidney)

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6
Q

What is the major active transport machinery that transports the sodium across the PT? and where is it located?

A

Na-K ATPase pump

  • It is located in the basolateral membrane (btw tubular epithelial cells and renal interstitium)
  • transports 3 Na out for 2 K in (at the expense of one molecule of ATP)

The result of NKA activity are decrease in intracellular Na concentration

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7
Q

How does sodium enter the the tubular epithelial cells from the tubule?

A

Passively

  • The potential energy of downhill movement of sodium at the luminal membrane is used in the transport of solutes such as glucose and amino acids. (exchangers and co-transporters)
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8
Q

What is the driving force of Bicarbonate and Cl- reabsorption?

A

Chloride and bicarbonate reabsorption follow sodium reabsorotion to maintain electro-neutrality

  • As the sodium is reabsorbed by an active transport process, the TF becomes more and more negative. This lumen negative electrical potential drives the transport of chloride and bicarbonate from the TF into the interstitial fluid.
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9
Q

What get reabsorbed more readily in the proximal tubule? Bicarbonate or Chloride?

A

Bicarbonate

  • Bicarbonate transport is coupled to NHE, this is an active transport process. Therefore, more HCO3 is reabsorbed in the proximal part of proximal tubule compared to chloride reabsorption.
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10
Q

What is coupled to bicarbonate reabsorption?

A

Coupled to proton secretion into the lumen

  • the intracellular enzyme carbonic anhydrase catalyzes formation of carbonic acid from carbon dioxide and water. Carbonic acid under physiologic pH dissociates into proton and bicarbonate. Proton is secreted into lumen, while bicarbonate is transported into interstitial fluid.
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11
Q

Mechanism of bicarbonate reabsorption

A

In the PT, proton secretion is mediated by the luminal membrane channel called NHE, which is an antiport. One hydrogen ion is secreted out when one Na is transpotted into the cell.
- Secreted H ion combines with the bicarbonate in TF to form carbonic acid. A membrane bound carbonic anhydrase enzyme in the luminal membrane breaks carbonic acid into carbon dioxide and water. Carbon dioxde freely diffuse into cell and across the cell into interstitial fluid. The bicarbonate formed during the production of proton by intracellular CA is actively transprted across the BL membrane into interstitial fluid by a Na/bicarboate co-transporter.

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12
Q

What drives the absorption of water from the PT?

A

Water absorption is driven by osmotic gradient.
- The massive solute transport results in a drop in the osmolarity of TF and an increase in omsolarity in the interstitial fluid.

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13
Q

How does water get reabsorbed from the PT to the interstitial fluid?

A
  1. Paracellular route (via high hydraulic conductivity through “leaky” epithelium)
  2. transcellular pathway (via aquaporins on the luminal membrane and basolateral membrane)
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14
Q

Name the locations of these aquaporins

  1. AQ-1
  2. AQ-4/5
  3. AQ-2
A

AQP-1: luminal membrane
AQP-4/5: basolateral membrane
AQP-2: distal tubule

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15
Q

In addition to the main mechanism of sodium transport, how else does sodium get reabsorbed?

A

Via Claudin-2 located in Tight junctions of the PT

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16
Q

How does Chloride get reabsorbed from the PT to the interstitial space?

A

Via passive diffusion through Claudin-4 located in Tight junctions of the PT

-although some may go through anion exchangers

17
Q

Once the fluid with salts is absorbed across the epithelium from the lumen of PT, how is it absorbed into the peritubular capillary

A
  1. Higher hydrostatic pressure in the interstitial space
    - due to fluid accumulation which favors fluid uptake into the capillaries
  2. low hydrostatic pressure in the peritubular capillary
    - portion of plasma is filtered through glomerular capillary bed. The rest is delivered to peritubular capillary.
  3. High oncotic pressure in peritubular capillary
    – Due to ultra filtration of plasma in the glomerular capillary the protein concentration in the peritubular capillary is increased resulting in increased oncotic pressure
18
Q

T or F: All solutes are absorbed at the same rate in the PT?

A

FALSE

  • Some are absorbed faster than others and some are not absorbed at all.
19
Q

How are Glucose, aa and organic acids absorbed in the PT?

A

They are absorbed by an active transport mechanisms

  • therefore, their concentration in the TF are reduced gradually along the length of PT
  • almost complete absorption!
20
Q

How is insulin reabsorbed?

A

Its NOT reabsorbed!

21
Q

How is glucose reabsorbed in the PT?

A

Glucose reabsorption - mediated by active transport via the Na+-Glu co-transporter in the luminal membrane of the epithelial cells

  • transports one molecule of glucose along with one equivalent of Na+ from the TF into the cytoplasm.
22
Q

T or F: The rate of glucose filtration is always equal to glucose reabsorption

A

FALSE
- Glucose is completely reabsorbed until it reaches a threshold level of plasma glucose which is 200-220 mg/dl

-unabsorbed glucose is excreted in urine

23
Q

What are some causes of glucosuria?

A

A.) physiological cause: pregnancy,
B.) pathophysiologic causes:
- diabetes mellitus
- mutation in SGLT1 and SGLT2, a condition known as familial renal glucosuria.

24
Q

How are AA absorbed?

A

Active transport

  • coupled to Na electrochemical gradient via co-transporters
  • almost completely reabsorbed
25
Q

How is potassium reabsorbed?

A
  1. Active transport coupled to Na+ electrochemical gradient
    - Low threshold, and therefore partially excreted continuously in urine.
  2. Passive transport via Claudins located in tight junctions
26
Q

What is urea? and how is it reabsorbed?

A

A metabolic byproduct of protein degradation and amino acid metabolism

  • The passive transport (slow and only 50% of filtered urea is reabsorbed)
27
Q

How can urea clearance be increased?

A

By increasing urinary flow

28
Q

What substances are SECRETED into the PT? how?

A
  1. Organic acids and bases
  2. Creatinine
  3. PAH (paraamino hippuric acid)
  4. Drugs
  • mostly by active transport
29
Q

Fact:
Substances that are freely filtered through glomerulus, but not reabsorbed can increase the TF osmolarity and cause diuresis, that is excessive water excretion in the urine.

A

Example:

Mannitol - typically used in the clinic to induce diuresis. (intracranial and intra ocular pressure and edema)
- It is an inert monosaccharide, not produced in the body nor degraded in the body. It is water soluble, freely filtered into GF, not reabsorbed nor secreted in the PT.