Renal transport mechanisms Flashcards
1
Q
What will happen if the ultraglomerular filtrate does not get modified?
A
- We would lose:
- 180L of water
- 25,200 mEq of sodium
- 19800 mEq of chloride
- 4320 mEq of HCO3-
- 14,400 mg of glucose
2
Q
What is meant by tubular reabsorption?
A
The reabsorption of large quantities of solutes and ions and it is highly selective
- It happens at a large scale, and is highly selective too
3
Q
What is meant by tubular secretion?
A
The significant amount of potassium ions, hydrogen ions, and a few other substrates that appear in urine
4
Q
What are the substances that are completely reabsorbed?
A
- Glucose
- Amino Acids
5
Q
What are the substances that are highly reabsorbed?
A
- Sodium ions
- Chloride ions
- Bicarbonate
- The rate of reabsorption and excretion varies depending on the needs of the body
6
Q
What are the substances that are poorly reabsorbed?
A
- Waste products:
- Urea
- Creatinine
7
Q
What are the transport mechanisms of tubular reabsorption?
A
1) Active
- Two conditions must be met, use of energy and the substance must be transported against its concentration gradient
- Solutes are transported transcellular
2) Passive
- The substance is transported along its concentration gradient without using energy
- Solutes are transported either transcellular or paracellularly (via diffusion)
8
Q
Describe the active transport of tubular reabsorption
A
- Pumps are used to push substances against the gradient and uses ATP by default
1) Primary: Occurs via the direct usage of ATP like the Na+/K+ ATPase pump
2) Secondary: Energy is built up by the movement of ions mainly by the Na+/Glucose and amino acid/Glucose pumps
9
Q
What is meant by the paracellular transport?
A
When a substance moves from one side to another through the tight functions following a concentration gradient
10
Q
What is meant by transcellular transport?
A
When a substance goes from one side to another by passing through the lumenal membranes inside the cell via active, passive, facilitated, or pinocytosis
11
Q
What is meant by bulk flow/solvent drag?
A
When a substance accumulates in the interstitial fluid (by any means) like water, it must go into the blood, this process is regulated by hydrostatic and oncotic forces
12
Q
What are the primary active transporters of the kidney?
A
- Sodium/Potassium ATPase
- Hydrogen ATPase
- Hydrogen potassium ATPase
- Calcium ATPase
13
Q
What are the examples of secondary active transporters?
A
1) Na+/Glucose co-transporter
2) Na/hydrogen counter transporter
- They are found at the luminal membrane of the PCT
3) AA/glucose
14
Q
What is the filtered load?
A
It is the glomerular filtration rate * plasma concentration
15
Q
What is meant by the excretion rate?
A
It is the urine concentration * urine ml/min
16
Q
How to calculate the reabsorption/secretion rate?
A
Filtered load (GFR * Plasma concentration) - Excretion rate (urine concentration * urine ml/min)
17
Q
What is meant by net reabsorption?
A
When the filter load is greater than the excretion rate (like the reabsorption of sodium)
18
Q
What is meant by net secretion?
A
When the filter load is less than the excretion rate (like PAH + “Para-aminohippuric acid”)
19
Q
Describe the reabsorption in the proximal tubule
A
The PCT has a high capacity for reabsorption and secretion where 65% of the filtered Sodium, potassium, HCO3, chloride, and water (osmosis) is reabsorbed
- Through the PCT the amount of sodium decreases but its concentration (osmolarity) remains the same as water is also reabsorbed
- All of the glucose and the amino acids are reabsorbed in the PCT, but their reabsorption is dependent on the availability and integrity of sodium and its channels
- Water reabsorption occurs by both paracellular and transcellular mechanisms
- Organic acids, bases, hydrogen ions, PAH are all secreted in the PCT
20
Q
What occurs at the early portion of the proximal convoluted tubule at the luminal side (brush border)?
A
- Cotransporters:
- Na/glucose
- Na/amino acid
- Na/Phosphate or lactate or citrate
- 1 Anti-porter:
- Na/H+
- In the brush border the sodium moves via facilitated diffusion while the other substances move via secondary active transport (using the energy from the movement of sodium ions)
- Reabsorption of bicarbonate ions
21
Q
How does the sodium get into the blood?
A
their concentration is high inside of the cell and thus they move via facilitated transport by the anti-porter Na/K ATPase which will get potassium ions into the cell
22
Q
How is the bicarbonate reabsorbed to the cell?
A
We said that an anti-port will transfer sodium into the cell and hydrogen out of the cell
1) Hydrogen will then combine with the filtered bicarbonate forming carbonic acid
2) Carbonic acid will then split into carbon dioxide and water via carbonic anhydrase
3) Carbon dioxide and water will enter the cell where they will get converted into carbonic acid via carbonic anhydrase
4) Carbonic acid will dissociate to form hydrogen and bicarbonate
5) The hydrogen will get excreted at the brush border and the bicarbonate will get transported into the blood by the Na+/HCO3- cotransporter or the Cl/HCO3- antiporter
23
Q
What occurs at the late proximal convoluted tubule?
A
- At the late PCT Cl- ions and urea will be concentrated which forms a gradient
- Transcellular movement of Cl- ions via the anti-porter Cl-/Formate
- Paracellular reabsorption of Cl- along with Na+ (sodium moves due to the buildup of + charge as the Cl”-“ is removed from the filtrate
- There is cellular and paracellular reabsorption of Cl- and Na+
24
Q
What is meant by positive sodium balance?
A
It is when the intake of sodium is greater than its excretion which will lead to greater water retention which might lead to edema
25
What is meant by negative sodium balance?
It is when the intake of sodium is less than its excretion and thus ECF volume contraction might occur (slide 16)
26
What are the different reabsorption % of sodium across the nephron?
1. 67% is reabsorbed at the PCT
2. 25% is reabsorbed at the thick ascending limb
3. 5% at the distal convoluted tubule
4. 3% at the collecting tubule
27
What is the quantity of sodium is filtered daily?
25,560 mEq/day
28
How much % of sodium is reabsorbed?
Reabsorbed is 99.4% (25,410 mEq/day)
29
How many percent of sodium is excreted daily?
>1% 150 mEq/day
30
What hormone helps us absorb sodium and in which part of the nephron?
Aldosterone does that by acting on the DCT and the cortical convoluted tubule as they have similar functions
31
What are the forces by which sodium is reabsorbed?
1. Sodium will diffuse into the cell down an electrochemical gradient and it is followed by water to maintain the isosmolality (67%) of solute and water is reabsorbed
2. Sodium will get transported across the basolateral membrane against its electrochemical gradient by the Na+/K+ ATPase pump and water will follow it
3. Ultrafiltration will result in the absorption of sodium, water, and others into the peritubular capillaries, this process is favored by the "peritubular oncotic pressure" therefore a high capillary oncotic pressure favors the bulk diffusion
32
What is the mechanism by which water, chloride, and urea reabsorption are coupled with sodium reabsorption?
1. Sodium reabsorption will increase the negative potential of the lumen which will result in the passive reabsorption of chloride ions
2. Sodium reabsorption will increase the water reabsorption and thus the luminal concentration of Cl- will increase which will increase its reabsorption
3. Sodium reabsorption will increase the water reabsorption and thus the luminal concentration of urea will increase, increasing its passive reabsorption
33
What is the effect of increased ECF volume on the reabsorption at the PCT?
The plasma proteins will decrease and the hydrostatic pressure will increase, this will result in a decrease in the fractional reabsorption
34
What is the effect of decreased ECF volume on the reabsorption at the PCT?
- The plasma protein concentration increases and the hydrostatic forces will decrease, this will increase the fractional reabsorption rate
- In addition to the act that in situations of hypovolemia the RAAS gets activated which will promote reabsorption at the DCT and the CT by stimulating the Na/H exchanger
35
What are the transport characteristics of the thin descending segment of the loop of Henle?
1. Highly permeable to water 20% of water gets reabsorbed
2. Moderately permeable to sodium and urea
- Since we are removing a high amount of water the the concentration of the solutes at the end of this segment becomes highly concentrated and the solution becomes hyperosmolar (The tubular fluid becomes progressively hyperosmolar)
36
What are the transport characteristics of the thin ascending segment of the loop of Henle?
1. It is impermeable to water but permeable to solutes
- At the end of the thin ascending segment the tubular fluid becomes hyposmolar
37
What are the transport characteristics of the thick ascending segment of the loop of Henle?
1. 25% of the filtrate reabsorption takes place
2. Ions like sodium, chloride, potassium, calcium, bicarbonate and magnesium are reabsorbed
3. Hydrogen ions are secreted
4. Impermeable to water
5. It has the NKCC co-transporters at its basolateral membrane (Na+/Cl-/K+ Co-transporter), sodium is also reabsorbed via the Na+/H+ exchanger
6. All ions leave the cell through channels except for Na+ which leaves via the ATPase
7. There is paracellular reabsorption of Na+, K+, Mg2+ and Ca2+ due to the slightly increased positive charge in the lumen
38
What is the MOA of the loop diuretics?
Diuretics like furosemide function by inhibiting the NKCC cotransporters
39
What happens at the early distal tubule?
- It forms part of the JG apparatus feedback control of GFR and renal blood flow
- The part after this forms the DCT (AKA Diluting segment), which:
1. Na+/Cl- cotransporter moves NaCl from the tubular lumen into the cell
2. Water and urea is impermeable (which makes the tubular fluid more diluted)
3. Reabsorption of Na, K, and Cl
- It reabsorbs 5% of the filtered sodium chloride
- Thiazides Diuretics are widely used to inhibit the Na+/Cl- treating disorders like hypertension and HF
40
What occurs at the late distal tubule (They have the same function as the cortical collecting tubule)?
- They have specialized cells which can be altered and affected by the aldosterone:
1. Principal cells
2. Intercalated cells
- Aldosterone works by enhancing the effects of the pump (Na/K ATPase) which will lead to an increase in sodium reabsorption and potassium secretion, when we increase the sodium being pumped out we will increase the potassium getting in, and Cl- reabsorption will take place as well
- Normally only 3% of the filtered sodium is reabsorbed here
- Reabsorbs
1. Sodium
2. Water
- Secretes
1. Potassium
41
What is the effect of sodium channel blockers on the late distal tubule
Sodium channel blockers like amiloride and triamterene, will block the sodium channels on the luminal membrane and therefore reduce the reabsorption of sodium
42
What are the effects of aldosterone antagonists on the late distal tubule?
Drugs like spironolactone and eplerenone, will compete with aldosterone for its receptor sites and thus decrease the sodium reabsorption and potassium excretion
43
What is the effect of ADH on the late distal tubule?
It will increase the permeability of the principal cells to water
1. ADH binds to V2-receptors (This binding results in a cascade of events that results in the expression of aquaporins 2 (AQP-2) on the luminal side of the cell
2. Expression of AQP2 will increase the water reabsorption
44
What are the types of intercalated cells?
1) Type A: function in acidosis ==> secrete hydrogen ions, reabsorb bicarbonate and potassium
2) Type B: function in alkalosis ==> secrete bicarbonate ions and potassium, reabsorb hydrogen ions
- Both are important in acid-base regulation
- They help in the elimination of H+ ions and the reabsorption of bicarbonate ions (one hydrogen is secreted by the cells and this is followed by the absorption of a bicarbonate ion)
45
What are the characteristics of type-A intercalated cells?
- They function in acidosis (they are important in eliminating hydrogen ions and reabsorbing bicarbonate in acidosis)
1. Hydrogen ions are secreted by the H+-ATPase and H+ K+-ATPase transporter
2. Potassium is reabsorbed
3. For each H+ ion secreted a bicarbonate ion is reabsorbed
- MOA:
1. Cell takes up CO2
2. CO2 is then combined with water to form carbonic acid
3. Carbonic acid will dissociate into bicarbonate ions and hydrogen ions
4. Hydrogen ions will then be secreted out of the cell into the lumen by either the H+/K+ ATPase or H+ ATPase
5. Bicarbonate will then get into the blood in exchange with Cl- via the Cl-/HCO3- exchanger
46
What are the characteristics of type-B intercalated cells?
- They function in alkalosis
1. Secretes bicarbonate into the tubular lumen and reabsorbs H+ ions
2. Secretes potassium
3. H+ and bicarbonate transporters are on the opposite sides of the cell membrane
- The only common thing is the formation of the carbonic acid
47
What is the final urine processing site?
The medullary collecting tubule, it determines the final urine output
48
What are the characteristics of the medullary collecting tubule?
- Absorption
1) Reabsorbs less than 5% of sodium
2) Reabsorbes less than 5% of water and it is controlled by ADH (ADH regulates the permeability of the MCT to water)
3) Unlike the cortical collecting tubule, the medullary collecting duct is permeable to urea, it reabsorbs urea to the interstitium via urea transporters forming a concentrated urine
- Secretion
4) H+ ions are secreted (regulating the acid-base balance)
49
What is the major function of the early proximal tubule?
Isosmotic reabsorption of solute and water (Na/glucose, Na/AA, Na/PO4 cotransporters, Na/H exchanger)
50
What are the hormones that act on the early proximal tubule?
1. PTH inhibits the Na/PO4 cotransporter
2. Angiotensin 2 stimulates the Na/H exchanger
51
What is the major function of the late proximal tubule?
Isosmotic reabsorption of solute and water (NaCl reabsorption driven by the Cl- gradient)
52
What is the major function of the thick ascending limb of loop of Henle?
1. Reabsorption of NaCl without water
2. Dilutes the tubular fluid
3. Reabsorption of Ca2+ and magnesium due to the positive potential of the lumen
- It has the Na-K-2Cl cotransporter
53
What hormones act on the thick ascending limb of the loop of Henle?
1) ADH stimulates the Na-K-2Cl cotransporter
54
What is the major function of the early distal tubule?
1. Reabsorption of NaCl without water
2. Dilution of the tubular fluid
55
What are the hormones that act on the early distal tubule?
PTH stimulates calcium reabsorption
56
What is the major function of the late distal tubule and collecting ducts (principal cells)?
1. Reabsorption of NaCl
2. K secretion
3. Variable water reabsorption
57
What hormones act on the late distal tubule and the collecting ducts (principal cells)?
1. Aldosterone stimulates Na reabsorption and K secretion
2. ADH will stimulate water reabsorption
58
What is the major function of the late distal tubule and collecting ducts (a-intercalated cells)?
1. Reabsorption of K+
2. Secretion of H+
- Aldosterone stimulates the secretion of H+ ions
59
What are the effects of angiotensin 2 on the proximal convoluted tubule?
- Formed in response to low blood pressure, it is the body's most potent sodium-retaining hormone, it stimulates:
1. Sodium-potassium ATPase transporter at the basolateral membrane
2. Sodium-bicarbonate cotransporter at the basolateral membrane
3. Sodium-hydrogen exchanger (NHE) at the luminal membrane
- It has the same effects on the loop of Henle, distal tubule, and collecting tubule
- FYI: angiotensin stimulates the release of ADH, and it constricts the efferent arteriole which (increases the GFR and reduces the hydrostatic pressure in the peritubular capillaries (since increased resistance decreases blood pressure), and these two effects favor filtration and reabsorption)
60
What is the site of action of the aldosterone and what are its tubular reabsorption effects?
- Site of action:
1. Collecting tubule and ducts
- Effects:
1. Increases sodium chloride and water reabsorption
2. Increases the secretion of potassium
61
What is the site of action of Angiotensin-2 and what are its tubular reabsorption effects?
- Site of action:
1. Proximal tubule
2. Tick ascending loop of henle
3. Distal tubule
4. Collecting tubule
- Effects:
1. Increases the reabsorption of NaCl and water
2. Increases the secretion of Hydrogen ions
62
What is the site of action of the ADH and what are its tubular reabsorption effects?
- Site of action:
1. Distal tubule
2. Collecting tubule and duct
- Effects:
1. Increases water reabsorption
63
What is the site of action of ANP and what are its tubular reabsorption effects?
-- Site of action:
1. Distal tubule
2. Collecting tubule and duct
- Effects
1. Decreases the reabsorption of NaCl
64
What is the site of action of the PTH and what are its tubular reabsorption effects?
- Site of action:
1. Proximal tubule
2. Thick ascending loop of Henle
3. Distal tubule
- Effects:
1. Decreases the reabsorption of PO4
2. Increases calcium reabsorption
65
How does our body regulate increased sodium intake?
- Incase of increased Sodium intake
1. Increased ECF and effective arterial blood volume (EABV) volume
2a) Decreased sympathetic activity
- Dilation of afferent arterioles (Increased GFR)
- Decreased sodium reabsorption (at the proximal tubule)
2b) Increased ANP
- Constriction of efferent arterioles (increased GFR)
- Decreased sodium reabsorption (collecting ducts)
2c) Decreased osmotic pressure
- Decreased sodium reabsorption at the proximal tubule
2d) Decreased RAA
- Decreased sodium reabsorption at the proximal tubule and collecting ducts
All of these effects will collectively increase the excretion of sodium
66
How does our body regulate decreased sodium intake?
Opposite of the previous card
