Renal structure and function: salts

Question 1

What cation is found in largest quantities in ECF?

Answer 1

Na, around 140mM Na, 5mM K

Question 2

What anion is found in the largest quantity in ICF?

Answer 2

K, around 140mM K, 5mM Na

Question 3

_____ is the main ion that is tightly controlled in the ECF and _____ is the main ion tightly controlled in the ICF

Answer 3

Na

K

Question 4

Total body Na _____ is sensed, not concentration.

Answer 4

Content

Question 5

Why is sodium content measured rather than sodium concentration?

Answer 5

The amount of salt, i.e. salt content is what influences plasma osmolality. Osmolality is usually maintained at the expense of volume changes, thus usually remains within narrow limits. The osmoreceptors control water intake by altering thirst and control renal excretion by altering ADH release. Changes in Na influence osmolality, for example if an animal eats a food high in Na, plasma osmolality will rise, inducing thirst and water absorption from the collecting ducts. This increases body volume and reduces salt concentration, but does not alter the amount of Na present. Therefore osmoregulation controls plasma Na by altering water balance, but does not control body Na content.

Question 6

What effect does altering Na concentration have on body volume?

Answer 6

If body Na is altered, the osmoregulatory system adjusts water balance and therefore body volume to maintain osmolality. Body volume can be controlled by altering Na content. The kidney controls Na excretion and therefore body volume

Question 7

What is hypernatraemia?

Answer 7

High ECF Na

Question 8

What are the potential complications of hypernatraemia?

Answer 8

Lots of fluid entering the blood due to increase osomolality of the blood can result in problems such as hydrocephalus

Question 9

How would you treat hypernatraemia?

Answer 9

Induce natruesis to cause a net loss of Na

Question 10

What is hypernatraemia?

Answer 10

Low ECF Na

Question 11

What are the potential complications of hyponatraemia?

Answer 11

Too little fluid in the blood (hypovolaemia)

Question 12

How would you treat hyponatraemia?

Answer 12

Induce Na retention to recover Na ions

Question 13

Name the four key hormones that control ECF Na.
1.
2.
3.
4.

Answer 13

Aldosterone
ADH
Natriuretic peptide
RAAS

Question 14

What biochemical class is aldosterone?

Answer 14

Mineralocorticoid

Question 15

What is the action of aldosterone?

Answer 15

Promote Na reabsorption in the CD

Question 16

Is aldosterone water or lipid soluble?

Answer 16

Lipid

Question 17

What response is seen when aldosterone binds to its receptors?

Answer 17

Transcription and translation of more mineralocorticoid receptors

Question 18

Aldosterone is inhibited in ______ and stimulated in ______

Answer 18

Hypernatraemia

Hyponatraemia

Question 19

Aldosterone stimulates Na reabsorption in the CD, what effect does this have on ECF volume and blood pressure?

Answer 19

Increases both

Question 20

What channels does aldosterone action act on?

Answer 20

Distal tubule Na/K-ATPases

CD apical ENAC

Question 21

With Na retention, _____ follows. This is what restores blood volume.

Answer 21

Water

Question 22

What effect does aldosterone have on the expression of Na/KATPases in the baolateral membrane of the cell?

Answer 22

Increases expression

Question 23

What effect does aldosterone have on the expression of Na channel on the apical membrane?

Answer 23

Increases expression

Question 24

Aldosterone does not markedly effect Na concentration, true or false?

Answer 24

True, this is because changes in osmolarity are largely maintained by a loss of water. Water and Na concentration is all relative, so if you get an increase in plasma concentration of Na, you will get a compensatory increase in water retention. The concentration may stay the same while the actual total body content of Na has increased.

Question 25

Thirst and ADH have a greater effect than aldosterone at maintaining water and Na balance, true or false?

Answer 25

True

Question 26

How does aldosterone act to counteract an increase in plasma K?

Answer 26

Increased release of aldosterone from the adrenal glands (ZG), increases renal secretion of K, resulting in increased excretion of K leading plasma K to come down to a normal level

Question 27

What are the sites of K excretion in the kidneys?

Answer 27

CD and DT

Question 28

How does secretion occur in the DT and CD?

Answer 28

Coupled to Na/K pumps

Question 29

In which direction does K travel in the epithelial cells of the DT when being secreted?

Answer 29

From epithelial cells to the tubular lumen via ion channels

Question 30

Plasma content of K is detected resulting in changes of aldosterone secretion, true or false?

Answer 30

False, K concentration is detected

Question 31

What is another name of ADH?

Answer 31

Vasopressin

Question 32

What biochemical class is ADH?

Answer 32

Peptide

Question 33

Where is ADH made?

Answer 33

Hypothalamus

Question 34

Where is ADH secreted from?

Answer 34

Posterior pituitary

Question 35

``` What 5 factors stimulate ADH release? 1. 2. 3. 4. 5. ```

Answer 35

``` Hypovolaemia Hypotension Dehydration Angiotensin II Sympathetic activation ```

Question 36

How does ADH conserve water?

Answer 36

Upregulates the amount of aquaporins in the apical membrane of principle cells in the collecting ducts and DT

Question 37

Osmoreceptors in the _____ detect changes in osmolarity in the ECF

Answer 37

Hypothalamus

Question 38

Increased ECF osmolarity _____ ADH secretion from the posterior pituitary

Answer 38

Increases

Question 39

As well as changes in plasma osmolarity, what else can stimulate ADH release?

Answer 39

Decline in blood volume and decline in blood pressure

Question 40

Where are changes in blood volume detected, and what are they detected by?

Answer 40

Volume receptors in the wall of the atria and veins

Question 41

Where are changes in blood pressure detected, and what are they detected by?

Answer 41

Baroreceptors in the aortic arch and carotid sinus

Question 42

Although osmoreceptors are more sensitive when it comes to ADH regulation, volume receptors can give the _____ _____ in ADH.

Answer 42

Greatest rise

Question 43

What does ANP stand for?

Answer 43

Atrial natriuretic peptide

Question 44

What effect does ANP have on Na balance?

Answer 44

Increases Na loss

Question 45

What are the major actions of ANP?

Answer 45

Renal vasodilation Increase in GFR Decreases renin release opposing the RAAS Decrease aldosterone release Decreased resorption/increased loss of Na Decreased ADH release

Question 46

Where is ANP stored and released from?

Answer 46

Right atrium

Question 47

What causes ANP release?

Answer 47

Release is stimulated by stretch of the right atrium

Question 48

Decreased blood volume results in ANP release, true or false?

Answer 48

False, increased blood volume results in ANP release

Question 49

What does RAAS stand for?

Answer 49

Renin-angiotensin-aldosterone system

Question 50

What level(s) does the RAAS work on?

Answer 50

Systemic and organ level

Question 51

What does the RAAS detect to bring bring about a physiological change?

Answer 51

Fall in blood pressure or volume

Question 52

Outline the physiological changes and how they activate the RAAS.

Answer 52

Fall in blood pressure is detected in the afferent arteriole, renin secreted from juxtaglomerular cells, renin converting angiotensinogen to angiotensin II which will act to increase blood pressure

Question 53

On what tissues does angiotensin II act and what actions does it have?

Answer 53

Adrenal gland, release aldosterone Pituitary, release ADH Arterioles, causes vasoconstriction Also acts on the PT (insertion of apical Na/H exchangers, basolateral Na/HCo3 ATPase and Na/K ATPases), TAL (insertion of apical Na/H and Na/K/2Cl exchangers) and CD (ENaC channels) These result in increase blood pressure or volume

Question 54

How does angiotensin II promote Na retention in the kidneys?

Answer 54

PT: insertion of apical Na/H exchangers, basolateral Na/HCo3 ATPase and Na/KATPases TAL: Na/H and Na/K/2Cl exchangers CD: ENaC channels

Question 55

Roughly how much Na is reaborsbed in the PT?

Answer 55

65%

Question 56

How does absorption of Na occur in the PT?

Answer 56

Na/KATPases, Na/H exchange transporters

Question 57

Roughly how much Na is absorbed in the LOH?

Answer 57

25%

Question 58

The thin ascending limb of the LOH is _____ to Na. Therefore, Na (and Cl) _____ out into the interstitial fluid.

Answer 58

Permeable | Diffuse

Question 59

Which pump in the thick AL utilises the Na gradient to co-transport one Na, one K and 2 Cl?

Answer 59

Na/K/2Cl cotransporter

Question 60

Ions are moved from the tubule lumen to the epithelial cells, but one ion passes back through to the lumen of the tubules through the energy requiring ROMK channel- which ion is this?

Answer 60

K

Question 61

The net charge of the tubule lumen is _____ due to the net removal of one Na and two Cl. K passes back into the tubule lumen.

Answer 61

Positive

Question 62

Roughly how much Na is reabsorbed from the DT?

Answer 62

5-8%

Question 63

How is Na and Cl reabsorbed in the DT?

Answer 63

NCC channels

Question 64

Roughly how much Na is reabsorbed in the CD?

Answer 64

5-10%

Question 65

How is Na taken up in the CD?

Answer 65

ENaC channels in principle cells

Question 66

When Na is taken up in the CD, what happens to the charge of the tubular fluid?

Answer 66

Becomes more negative

Question 67

How does a more negative lumen in the CD (due to Na uptake by ENaC cells) influence Cl uptake?

Answer 67

Increases paracellular Cl uptake

Question 68

Are principle cells responsive to ADH?

Answer 68

Yes

Question 69

What type intercalated cells are present in the CD?

Answer 69

B-intercalated cells

Question 70

What is present on B-intercalated cells in the CD that creates a gradient that is used to drive the secretion of HCO3- coupled to Cl absorption?

Answer 70

H+ATPases

Question 71

What happens if an animal Na laods or ECF volume or blood pressure is high?

Answer 71

Renin secretion is inhibited Aldosterone-dependant Na resorpton is inhibited Excess Na is excreted in the urine (action of ANP)

Question 72

Where is the majority of K found in the body?

Answer 72

ICF

Question 73

What is a method of short term control K in the body?

Answer 73

ECF to ICF shifts of potassium

Question 74

What are two mechanisms that controls K excretion longer term? 1. 2.

Answer 74

Renal excretion | GI excretion

Question 75

Which of renal or GI excretion causes the most loss of K from the body?

Answer 75

Renal excretion

Question 76

In the PT, _____% of K is reabsorbed.

Answer 76

65%

Question 77

Similar proportions of _____, _____ and _____ are reabsorbed in the PT

Answer 77

Na, K, water

Question 78

What results in K being constantly pumped into the tubular epithelium?

Answer 78

Na/KATPases

Question 79

Once pumped into the epithelium, K can have two fates, what are these?

Answer 79

Leak into interstitium | Pumped out of the epithelial cells by Cl/K pumps

Question 80

Some K moves into the filtrate in the TDL, but this is countered by movement of K out of the loop and into the CDs. The net result is some _____ of K across the medullary interstitum.

Answer 80

Recycling

Question 81

Roughly how much K is reabsorbed in the TAL?

Answer 81

30%

Question 82

How does K enter the epithelial cells of the TAL?

Answer 82

Na/KATPases

Question 83

What is the name of the transporters that transport Na, K and 2Cl into the epithelial cells?

Answer 83

NKCC2 transporters

Question 84

Apart from the NKCC2 transporters, what other channels are present in the TAL that pump K into the epithelial cells?

Answer 84

Na/KATPases

Question 85

What transporters pump K out of the epithelial cells of the TAL?

Answer 85

K/Cl transporters

Question 86

By what other route can K be reabsorbed in the TAL?

Answer 86

Paracellularly due to the positive charge of the tubule contents

Question 87

95% of K is reabsorbed before the filtrate reaches the CD's, true or false?

Answer 87

True

Question 88

There are two cell types in the collecting tubules and ducts with opposing actions with regards to K absorption and secretion. What are these cells called and what is their function?

Answer 88

Principle cells secrete K | Intercalated cells reabsorb K

Question 89

_____ cells reabsorb K while _____ secrete K.

Answer 89

Intercalated | Principle

Question 90

K _____ outweighs K _____ in the CD.

Answer 90

Secretion | Reabsorption

Question 91

How is secretion of K mediated in the epithelial cells of the CD?

Answer 91

Driven by Na/KATPases in the basolateral membrane pumping K into the cell at the basolateral surface. At the apical surface, K enters the tubular fluid via KCC channels.

Question 92

Why is there a negative charge in the tubular fluid?

Answer 92

Due to net Na reabsorption in the PT and LOH

Question 93

How does flow rate effect K secretion?

Answer 93

If flow rate is high, lots of K can be secreted as this keeps the charge in the tubular lumen negative, which increases K secretion.

Question 94

What are SK and BK channels and where are they found in the kidneys?

Answer 94

Big K channels | Collecting ducts

Question 95

When are BK channels activated?

Answer 95

When flow rate of tubular fluid is high to promote K secretion

Question 96

Type A intercalated cells are involved in the reabsorption of K in the CDs. How do they function?

Answer 96

Driven by apical H/KATPase which actively pumps K into the cell and H out of the cell. K ions then leave through basolateral K channels and are reabsorbed.

Question 97

High plasma K results in the release of what hormone?

Answer 97

Aldosterone

Question 98

What is the level does K have to get to in the serum for an animal to be considered hyperkalaemic?

Answer 98

5.5mmol/L

Question 99

Clinical effects of hyperkalaemia are seen at 7.5mmol/L, true or false?

Answer 99

True

Question 100

What is the most common reason for hyperkalaemia?

Answer 100

Impaired renal function

Question 101

What are the four most common causes of hyperkalaemia?

Answer 101

Internal redistribution of K is impaired Increased K leak in muscles Structural abnormalities in the kidney Functional abnormalities in the kidney

Question 102

What can cause alteration in internal redistribution of K?

Answer 102

Insulin resistance, use of beta-blocker

Question 103

What can cause high K leak within muscle cells?

Answer 103

Cell destruction, acidaemia

Question 104

What are the consequences of structural abnormalities in the kidney?

Answer 104

Decreased filtration, reduced ability to compensate for rapid changes in K load (or any other ion)

Question 105

What can cause functional abnormalities in the kidney?

Answer 105

Decreased luminal flow, metabolic acidosis, hypoaldosteronism

Question 106

``` Chronic hyperkalaemia is largely due to reduced renal excretion. Name 5 causes of this. 1. 2. 3. 4. 5. ```

Answer 106

``` UT trauma UT obstruction Use of K sparing diuretics Hypoaldosteronism Hypoadrenocorticism Anuric renal failure Use of ACE inhibitors ```

Question 107

What level in the blood does K have to reach before an animal is considered hypokalaemic?

Answer 107

Less than 3.5mmol/L

Question 108

What conditions can cause hypokalaemia?

Answer 108

Anorexia, CKD, IV fluids on too high a flow rate

Question 109

What are the four most common causes of hypokalaemia?

Answer 109

Increased renal loss Increased gastric loss Shift in biodistribution from ECF to ICF Iatrogenic

Question 110

What can cause increased renal loss of K?

Answer 110

CKD, inability to concentrate urine and reabsorb K | Diureteic therapy that increases tubular flow rate

Question 111

Increased gastric loss of K is often caused by _____ and _____.

Answer 111

V+ and D+

Question 112

What can cause changes in biodistribution of K?

Answer 112

Insulin treatment | Hyperthyroidism

Question 113

What are some possible causes of iatrogenic damage resulting in hypokalaemia?

Answer 113

Use of nephrotoxic drugs, laxatives, too aggressive bicarbonate therapy when treating acidosis