4a.) Control of Volume Flashcards

1
Q

What is the major osmotically effective solute in ECF?

A

Na+

(Cl- also plays role)

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2
Q

What is meant by soidum ion balance?

Describe positive and negative balance

A

Sodium balance= process of matching the amount of sodium ingested to the amount of sodium excreted

  • Positive balance: ingested > excreted
  • Negatvie: ingested < excreted

REMEMBER: we are talking about the total amount of sodium, not the concentration of sodium

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3
Q

Generally speaking, does altering the amount of sodium that is reabsorbed or excreted change the osmolality of ECF?

A

It doesn’t change osmolality because if say more sodium is reabsorbed, more water will be reabsorbed and vice versa

Excpetion in descending loop of Henle? Check???

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4
Q

Where are low pressure baroreceptors found?

How do they work?

A

Low pressure baroreceptors found in the atria and pulmonary vasculature. If they detect a decrease in blood pressure they will send signal to the brainstem via the vagus nerve and consequently sympathetic output will be increased and ADH will be released. (remember sympahtetic increases vasoconstriction and increases HR).

If these low pressure baroreceptors are distended they send signals to decrease sympathetic output.

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5
Q

Low pressure baroreceptors respond to total venous volume; true or false?

A

TRUE

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6
Q

In general, what % change in pressure is required to stimulate and evoke response from both low and high pressure baroreceptors?

A
  • Low presssure: 5-10% decrease in BP
  • High pressure: 5-10% increase in BP
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7
Q

Where are the high pressure baroreceptors?

Describe how they work

A

High pressure baroreceptors found in aortic arch and carotid sinus. Detect stretch and hence increase in blood pressure, send signals to medulla oblongata in brainstem to increase parasympathetic stimulation to heart (to decrease HR) and decrease sympathetic stimulation to smooth muscles in vasculature to decrease TPR

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8
Q

Describe the bainbridge reflex

A

Stretch receptors in right atria detect changes in blood volume. Increased blood volume stretches the receptors and hence signal is sent to medulla which then decreases parasympathetics to heart and increase sympathetics to heart to increase HR

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9
Q

Which reflex, baroreceptor or Bainbridge, dominates when blood volume is high?

A

Bainbridge

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10
Q

Which reflex, baroreceptor or Bainbridge, dominates when blood volume is diminished?

A

Baroreceptor

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11
Q

How do kidneys respond to an increase in volume of ECF? (Brief, simple explanation)

How do kidneys respond to a decrease in volume of ECF? (Brief, simple explanation)

A

Increase excretion of sodium and chloride ions and hence water.

Decrease in excretion of sodium and chloride ions and hence water

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12
Q

If we need to adjust plasma volume, why can’t we just move water to or from our plasma?

A

Because only moving water would change the plasma osmolarity. We need to add or remove an isosmotic solution to change volume so that we don’t change osmolarity of plasma. Hence, we move osmoles actively (number of moles of osmotically active particles) and water will follow passively.

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13
Q

Which part of urinary system is classed as ‘inside’ body and which is classed as ‘outside’ body’?

A

Lumen of kidney system (from when plasma filters through glomerulus into bowmans capsule) is outside body

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14
Q

Describe paracellular and transcellular transport

A

Paracellular: through intercellular space (between cells)

Transcellular: transport through cell- hence including its apical and basolateral membrane

NOTE: lumen is the lumen of nephron

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15
Q

Describe where the luminal/apical membrane is

Describe where the basal/basolateral membrane is

A
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16
Q

Which part of the nephron don’t absorb water

A
  • Ascending loop of Henle
  • Distal convoluted tube

(THEY HAVE NO AQUAPORINS)

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17
Q

Where is most of sodium reabsorbed?

A

Proximal tubules (67%) and ascending loop of Henle (25%) absorb most of sodium. Remaining sodium is reabsorbed in a precisely regulated manner by distal tubules and collecting ducts to maintain accurate salt balance

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18
Q

How many segments do we divide the proximal convoluted tubules into and why?

A

Divide into 3 but we will consider:

  • Segment 1
  • Segments 2 & 3 together

… must consider separately as they use different transporters or channels

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19
Q

Describe reabsorption in segment 1 of the proximal convulted tubule

A
  • Basolateral membranes of tubular cells contain Na+/K+ ATPase; pump Na+ against concentration gradient into interstitium. Increases [Na+] in interstitium so that Na+ moves down conc gradient into blood. Movement of blood out of tubular cells creates conc gradient between filtrate and tubular cells so Na+ moves from filtrate into tubular cells via apical membranes passively
  • Na+ gradient drives co-transport of Na+ with bicarbonate, amino acids or carboxylic acids, glucose and phosphate
  • Water diffuses through aquaporin 1 and paracellulary into interstitium
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20
Q

Explain why a larger amount of sodium is reabsorbed in segment 1 of proximal convulted tubule compared to segments 2 and 3 of PCT

A
  • S1: cell junctions slightly leaky, which limits concentration gradient that can be established, but rate of transport higher
  • S2 & S3: cell junctions not as leaky so larger concentration gradient can be established but rate of transport is slower
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21
Q

Where is all glucose, aa and lactate absorbed?

A

Proximal convoluted tubule

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22
Q

Explain why diabetics have glucosouria

A

The amount of plasma glucose exceeds the transport maximum

23
Q

Describe the absorption of bicarbonate in segment 1 of the proximal convoluted tubule

A
  • NaHCO3 dissociate into Na+ and HCO3-
  • Na+/H+ exchanger uses Na+ gradient to reabsorb sodium and secrete H+ into filtrate
  • H+ and HCO3- combine to form H2CO3
  • Carbonic andhyrdase converts H2CO3 into H20 and CO2 which diffuse transcellulary across apical membrane
  • Carbonic anhydrase recombines H2O and CO2 to reform H2CO3
  • H2CO3 dissociates into H+ and HCO3-
  • H+ used in NHE
  • HCO3- transported into blood using energy dissipated from movement of Cl- down its concentration gradient
24
Q

In the proximal tubule, ions are being moved; how is the charge inside the cell kept the same?

A

Secretion of H+ through apical membrane balanced with baolateral exit of HCO3-.

25
Describe what happens to Cl- concentration as you move along proximal convoluted tube and explain why this is of importance
Cl- concentration increases (because the proportional amount of Cl- in filtrate has increased. Lost some water and other ions but not lost any Cl- yet)
26
Explain what is meant by ordinate
27
Describe reabsorption in segement 2 of the proximal convoluted tubule
* Since positively charged Na+ ions have been leaving lumen, lumen is left with negative charge * Negative charge of lumen, along with increased [Cl-] in lumen repels Cl- hence Cl- leave lumen via paracellular transport * Loss of Cl- creates +ve charge in lumen * +ve charge repels Na+ hence it moves out of lumen via NHE down it's concentration gradient * H+ from NHE needs anion to join with so that we aren't just adding to the +ve lumenal charge. Anion comes from anion exchanger (Cl- and usually HCO3-) * Molecule formed from H+ and anion moves across membrane (see bicarb movement in other flashcard). It dissociates in cytoplasm and products are used in the transporters * Water moves paracellularly and transcellulary via aquaporin 1 * Cl- ions leave cell alone, in exchange for another anion or with potassium
28
Are there many different sodium-dependent amino acid transporters?
Yes, at least 7 different transporters
29
What causes water absorbed from lumen of PCT to move into peritubular capillaries? (3)
* **Increased osmotic gradient:** solute reabsorbed from lumen of PCT into tubular cells. Then move into interstitium hence there's high concentration of solutes in interstitium so they move down conc gradient * **Increased oncotic force from peritubular capillaries**: since ions and water has been filtered out of blood at glomerulus, there is an increased [plasma proteins] in peritubular capillaries hence there is a greater oncotic force * **Increased hydrostatic force in interstitium**: water been reabsorbed
30
What % of water does proximal convoluted tubule reabsorb?
65%
31
Describe the effect of angiotensin II on the PCT
Angiotensin II stimulates Na+ reabsorption in PCT when BP is low
32
Amiloride is a diuretic that inhibits ENaC in DCT; however it also has an effect in PCT. Describe this effect
Amiloride blocks NHE in PCT abolishing ~80% of action of angiotensin II. Remember, angiotensin II stimulates Na+ reabsorption in response to low BP hence an individual on amiloride may have problems regulating blood pressure
33
Describe what happens in PCT, in terms of transporters, in response to arterial BP increasing
* Reduction in number of NHE transporters * Reduced Na+/K+ ATPase activity ... causes reduction in sodium reabsorption in proximal tubule hence reduction in water reabsorption. Leading to natriuresis and diuresis
34
# Define: * Natriuresis * Diuresis
* Natriuresis: excretion of sodium * Diuresis: excretion of water
35
Is there a concentration gradient between the lumen and intersitium in the loop of Henle (as we move move from kidney cortex to papilla)? What are the consequences of such a gradient in terms of water and Na+ and Cl- ions?
Yes, there is an increasing concentration gradient as we descend the loop of Henle and move from cortex to papilla. This concentration gradient allows for paracellular reabsorption of water in the descenidn limb. As a result, sodium and chloride ions become concentrated in the descending limb ready for active transport in the ascending limb.
36
Describe reabsorption of Na+ and Cl- in the thin ascending limb
Ions have been moved out of lumen and into interstitium (and then into blood) but this has created an interstitial concentration gradient from cortex to papilla (concentration in intersitium higher in papilla). This caused water to move out of lumen and into interstitium (and then into blood) in the descending limb. As a result, there is a high concentration of Na+ and Cl- in thin ascending limb hence both ions are passively reabsorbed by paracellular transport
37
Describe reabsorption in the thick ascending limb
* Key transporter is NKCC2 * NKCC2 uses Na+ gradient (which is still being maintained by Na+/K+ ATPase) to transport 1 Na+, 2 Cl- and 1 K+ (total removal of change of charge is 0) * HOWEVER, ROMK (renal outer medullary K+ channel) allows K+ to re-enter tubule * This gives lumen a +ve charge * +ve charge of lumen repels +ve ions e.g. Na+, K+, Mg2+, Ca2+, NH4+ hence the positive lumen drives the paracellular transport of the above molecules
38
What transporter, and in which region of nephron (mainly), do loop diuretics such as Furosemid target? State 2 potential side effects? *HINT: one to do with potassium, one to do with MD*
NKCC2 channel * Hypokalaemia is potential side effect as blocking NKCC2 decreases potassium reabsorption * MD cells wont be able to detect changes in NaCl and hence tubuloglomerular feedback will be inhibited
39
What transporter, and hence what region of nephron, do K+ sparing diuretics such as Spironalactone inhibit?
ROMK Blocking ROMK can: * Reduce effectiveness of NKCC2 as K+ not pumped back into lumen and it's needed for NKCC2 * Lumen wont' be left +ve charged hence paracellular transport of positive ions won't be as effective
40
Compare and contrast the absorption of water and NaCL in the ascending and descending limb of Loop of Henle
Descending limb: * Reabsorbs water, not NaCl Ascending limb: * Doesn't reabsorb water, but reabsorbs NaCl
41
Which limb of Loop of Henle is known as diluting segment?
The ascedning limb as it reabsorbs NaCl but not water
42
Compare the tonicity of fluid leaving loop of Henle to the plasma
Fluid leaving L.O.H is hypoosmotic (more dilute) than plasma
43
What hormone affects the water permeability of the distal convoluted tube?
ADH (released when BP is low) increases expression of aquaporins in DCT to increase water absorption/permeability
44
Water permeabilty of early DCT is fairly low; true or false
True
45
Describe reabsorption in early distal convoluted tube
* Fluid entering DCT is hyposmotic * NCCT transports Na+ and Cl- into tubular cells using Na+ gradient * Na+ leaves via Na+/K+ ATPase * Cl- leaves down concentration gradient or coupled with K+ down concentration gradient
46
What transporter, and hence what region of nephron, do thiazides target?
NCCT transports in DCT
47
Describe reabsorption in late DCT
* Na+ and Cl- move into tubular cell via NCCT using sodium concentration gradient * Na+ also moves down conc gradient through ENaC (epithelial sodium channel) * However, NCCT is electroneutral but ENaC isn't hence lumen becomes negatively charged * Netative lumen repels Cl- and drives paracellular uptake of Cl- * Ca2+ also absorbed via Ca2+ channels. As soon as in cytoplasm it binds to calbindin and then is transported out cell, down it's conc gradient, using NCX using energy from Na+ gradient or via calcium ATPase
48
Collecting duct divided into what two regions? What two cell types are in the cortical collecting ducts?
* Cortical * Medullary regions Principal cells & intercalated cells found in CCD
49
What percentage of sodium is reabsorbed in distal convoluted tubule?
5-8%
50
What % of sodium is reabsorbed in collecting ducts?
2-5%
51
Describe reabsorption in principal cells of cortical collecting ducts
* Reabsorption of Na+ via ENaC down Na+ gradient * Loss of Na+ from lumen means there is negative charge in lumen * Negative lumen repels Cl- driving paracellular reabsoprtion of Cl- * Varaible amount of water uptake through AQP
52
What % of cells are principal and what % are intercalated in the cortical collecting duct?
70% principal 30% intercalated
53
Describe reabsorption in intercalated cells of cortical collecting ducts
* **Have no Na+/K+ ATPase!** * But have H+ ATPase on basolateral membrane and H+/K+ ATPase on apical membrane this means [H+] in tubular cell is low so there is a H+ gradient going into the tubular cell CHECK WITH HUDMAN
54
Summarise how much water and Na+ is absorbed in each part of the nephron