Regulation of ECF Volume

Question 1

Since H2O can freely cross all cell membranes, body fluids are all in…

Answer 1

Osmotic equilibrium meaning TBW distribution between cells and ECF is determined by osmotically active particles

Question 2

What osmotically active particles regulate the ECF volume?

Answer 2

Na+ and Cl-

Question 3

What ions regulate ICF?

Answer 3

K+

Question 4

Changes in Na+ content of the ECF affects what?

Answer 4

ECF volume
Volume of blood perfusing tissues and circulating blood
Blood pressure

Question 5

So if Na+ has such a large affect on blood volume and BP, what is regulation bound to be dependent on ?

Answer 5

High and low pressure baroreceptors

Question 6

What is the response to a low ECF volume (hypovolaemia)?

Answer 6

A low ECF will result in low venous pressure = a low atrial pressure which decreases end diastolic volume, decreasing stroke volume, CO and BP

This reduces carotid baroreceptor inhibition of sympathetic discharge

The increase of S discharge results in vasoconstriction = an increase in total peripheral resistance which increases BP

Question 7

How are some ways a low ECF can occur?

Answer 7

Salt and H2O loss via vomiting, diarrhoea or excess sweating

Question 8

What does an increase of ADH do to the renal system?

Answer 8

Increases renal artery constriction -vasopressin

Increase in renin leading to increase in angiotensin 2

Angiotensin 2 increases proximal tubule salt and water reabsorption and increases aldosterone which acts on the distal tubule also increasing salt and water reabsorption

Question 9

How does angiotensin 2 increase salt reabsorption from the proximal tubule?

Answer 9

It decreases peritubular capillary hydrostatic pressure (therefore increasing oncotic pressure favouring reabsorption)

Question 10

How does vasoconstriction caused by ADH affect afferent and efferent arterioles and therefore glomerular filtration?

Answer 10

Autoregulation maintains GFR and the VC of afferent and efferent means little effect on GFR

Only causes an effect if volume depletion is so low that there is a large drop in mean BP

Question 11

Regulation of distal tube reabsorption is under control of…

Answer 11

Aldosterone

Question 12

What are juxtaglomerular cells?

Answer 12

Specialized smooth muscle cells of the afferent arteriole in the area of the glomerulus.
It contains large epithelial cells with plentiful granules

Question 13

What are Juxta-glomerular cells (JG cells) closely related to?

Answer 13

The macula densa - a histologically specialized loop of the distal tubule

Question 14

What do JG cells do?

Answer 14

Produce the hormone renin

Question 15

What triggers JG cells to make renin ?

Answer 15

1. A decrease in afferent arteriole pressure (decrease in BP)
2. Increase sympathetic nerve activity via B1 effect
3. In the macula densa cells in the distal tubule detect low levels of NaCl, which means a low BP
4. Negative feedback loop of high levels of angiotensin 2
5. ADH inhibits renin release

Question 16

What does renin do?

Answer 16

Splits angiotensinogen into angiotensin 1

Angiotensin 1 is converted to 2 by ACE enzyme

Question 17

Where is ACE enzyme found?

Where does most conversion take place?

Answer 17

In vascular endothelium - most conversion takes place in the pulmonary circulation

Question 18

What does angiotensin 2 do?

Answer 18

Vasoconstriction and increased CV response to increase BP

Stimulates hypothalamus to make ADH and increase thirst

Stimulates adrenal cortex to made aldosterone

Question 19

What does aldosterone do ?

Answer 19

Passes in the blood to the kidney where it stims distal tubule Na+ ion reabsorption

Question 20

What is the rate limiting step of the RAAS system?

Answer 20

The release of renin since angiotensinogen is always present in the plasma

Question 21

When the GFR increases as a result of angiotensin 2 - what is the feedback loop to stop it getting too high?

Answer 21

Since flow increases - flow past macula densa also increases

This sends signal to afferent arteriole constriction it which increases resistance, decreasing hydrostatic pressure which decreases GFR

Question 22

Complex case - What happens to a person suffering from severe diarrhoea, who has lost 3l of salt and water (from ECF) and drinks 2 l of pure water (no salt)

Answer 22

Leads to opposing inputs to ADH secreting cells

1. A decrease in the ECF osmolarity leads to inhibition of ADH via osmoreceptors
2. A decrease in ECF volume (by 1L) will increase ADH via baroreceptors

Question 23

So what ADH response is more important?

Answer 23

Normally osmolarity is the main determinant of ADH

But if there is sufficient volume change which compromises brain perfusion then ECF volume becomes the 1y drive

So body works to fix ECF volume first then regulates osmolarity

Question 24

Start of lecture 2

Answer 24

OK

Question 25

What is ANP and what does it do?

Answer 25

Atrial Natriuretic Peptide

Does opposite of aldosterone and causes excretion of Na+

Question 26

What happens if you administer aldosterone to normal subjects on a good Na+ intake?

Answer 26

Na+ retention and K+ loss
2-3kg weight gain due to water reabsorption

After a couple of days there will be spontaneous diuresis due to ANP release which balances water and Na+ levels BUT K+ loss still persists

Question 27

How does this affect Conn’s syndrome patients?

Answer 27

Since Conn’s is hyperaldosteroneism - they will have K+ depletion but not have high levels of Na+ (due to ANP)

Question 28

What is osmotic diuresis

Answer 28

Is the increase of urination rate caused by the presence of certain substances, such as a high conc. of glucose, in the kidneys

Question 29

How does uncontrolled DM wreak kidney function via osmotic diuresis?

Answer 29

The high plasma conc. of glucose exceeds the kidneys ability to reabsorb it all

So glucose in tubule exerts osmotic effect retaining H2O in tubule

This decreases Na conc. in tubule lumen creating a gradient from which Na will leave the intersitium and go into the tubule

= Increased retention of Na and H2O

Question 30

How does this increased retention of Na and H2O in the proximal tubule due to osmotic diuresis affect the loop of henle function?

Answer 30

In descending limb - water doesn’t move out into interstitium as much due to glucose and excess Na+ exerting an osmotic effect

In ascending limb - fluid is now less concentrated - NaCl pumps cannot create a good medullary interstitium gradient

This leads to a reduced ability to reabsorb water and NaCl

Question 31

If osmotic diuresis keeps up, what will happen in the loop of henle?

Answer 31

Medullary interstitium gradient is destroyed

Question 32

What does osmotic diruesis do to the RAAS system?

Answer 32

Macula densa detects high flow of NaCl so thinks ECF volume is high and inhibits renin release

This further stops Na reabsorption at distal tubule

Question 33

Why is ADH release ineffective against osmotic diuresis?

Answer 33

Because the loop of henle medullary interstitial gradient has been run down/abolished

Question 34

So in uncontrolled diabetes why does a hyperglycemic coma happen?

Answer 34

Reduced ECF volume reduced O2 perfusion to brain

Question 35

So in uncontrolled diabetes why does a hypoglycemic coma happen?

Answer 35

Reduced glucose levels for brain

Question 36

What is an important point about K+ ions in the loop of henle?

Answer 36

The NaCl pumps in the ascending limb also involve K ions - which is why loop diuretics cause K+ ion wasting