ECF Volume Regulation 1 & 2

Question 1

One of the most important aspects of the ECF regulated by the kidney is its ______

Answer 1

volume

Question 2

Since H2O can freely cross all cell membranes, the body fluids are in osmotic equilibrium, so that the distribution of TBW between cells and ECF is determined by what?

Answer 2

the number of osmotically active particles in each compartment

Question 3

name major ECF and ICF osmoles

Answer 3

Na+ and Cl- are the major ECF osmoles. K+ salts are the major ICF osmoles

Question 4

Regulation of ECF volume = Regulation of body ___

Answer 4

Na+

Question 5

describe the distribution of body water

Answer 5

Question 6

what will changes in Na+ content of the ECF lead to?

Answer 6

changes in ECF volume and therefore will affect the volume of blood perfusing the tissues = effective circulating volume and therefore BP

Question 7

what is regulation of Na+ dependent on?

Answer 7

Na+ is basically dependent on high and low P baroreceptors

Question 8

Describe the renal response to a decreased ECF volume (hypovolaemia)?

Answer 8

increase salt and H2O loss as in vomiting, diarrhoea or excess sweating = decreased PV = decreased venous P = decreased VR = decreased atrial P = decreased EDV = decreased SV = decreased CO = decreased BP = decreased carotid sinus baroreceptor inhibition of sympathetic discharge.

= increased Sympathetic discharge = ­increased VC = ­increased TPR =­ increased BP towards normal

Question 9

what does increased sympathetic discharge cause on the kidney?

Answer 9

1. ­ increased renal VC nerve activity = increased­ renal arteriolar constriction and an increase ­in renin
2. ­increased renin = increased angiotensin II = decreased peritubular capillary hydrostatic P (+ the increased osmotic pressure­) = increase­ Na+ reabsorption from the proximal tubule and therefore less Na+ excreted

­­­­increased renin =­­ increased angiotensin II = ­increased­ aldosterone = ­increased­ distal tubule Na+ reabsorption and therefore less Na+ excreted

Question 10

what are changes in the proximal tubule Na+ reabsorption due to?

Answer 10

Changes in proximal tubule Na+ reabsorption are due to changes in the rate of uptake by the peritubular capillaries.

Determined by osmotic pressure

Question 11

increase in Na+ reabsorption is because of greater reabsorptive forces in the peritubular capillaries

what happens if If have lost NaCl and H2O is lost

Answer 11

more of the “wet stuff”, then osmotic pressure increases even more than normal (ie > than that due to loss of filtration fraction) so can reabsorb up to 75% of the filtrate at the proximal tubule

(So reabsorptive range in proximal tubule; 65% in volume excess to 75% in volume deficit. Big range of volume just because of changes in Starling’s forces.)

GFR remains largely unaffected

Question 12

How is GFR maintained in time of excess or deficits in volume

Answer 12

Autoregulation maintains GFR and the VC of afferent and efferent means little effect on GFR until volume depletion severe enough to cause considerable decreased MBP

Question 13

when volume compromised:

Oncotic pressure is ______ as we are volume compromised and volume of blood protein stays the same so higher ______ pressure so drive to take up water is even bigger

Answer 13

higher

oncotic

Question 14

Regulation of distal tubule Na+ reabsorption is under the control of what?

Answer 14

the adrenal cortical steroid hormone, aldosterone

Very important in the long-term regulation of Na+ and ECF volume

Question 15

Aldosterone secretion is controlled by reflexes involving what?

Answer 15

Aldosterone secretion controlled by reflexes involving the kidneys themselves

Question 16

what are Juxtaglomerular cells (JG)?

Answer 16

Smooth muscle of the media of the afferent arteriole, just before it enters the glomerulus has become specialized, containing large epithelial cells with plentiful granules = Juxtaglomerular cells (JG)

Question 17

what are JG associated with and what does it form?

Answer 17

They are closely associated with a histologically specialized loop of the distal tubule = the macula densa

The two together form the Juxtaglomerular apparatus

Question 18

what do JG cells produce?

Answer 18

JG cells produce the hormone renin

Question 19

what does renin act on?

Answer 19

a proteolytic enzyme which acts on a large protein in the a2-globulin fraction of the plasma proteins = angiotensinogen

Renin splits off the decapeptide angiotensin I which is then converted by enzymes in the endothelium to the active octapeptide = angiotensin II

Question 20

what is the rate limiting step invovle dinth e prodcution of angiotensin 2?

Answer 20

ACE enzyme found everywhere

How much renin is present is the only rate limiting step

Question 21

whata re all the effects of angiotensin 2?

Answer 21

Vasoconstrictor

Increased cardiovascular response like heart rate

Increased the release of ADH to maintain volume and reabsorb everything and also increase thirst to increase intake, aiming to restoring volume

AGN 2 also stimulates adrenal cortex to release aldosterone and this increases sodium reabsorption in distal tubule cells

Question 22

what is the enzyme involved in the angiotensin pathway? and where is it found and act?

Answer 22

The enzyme = angiotensin converting enzyme = ACE

It is found throughout the vascular endothelium, but the greatest proportion of the conversion occurs as the blood passes through the pulmonary circuit, but all of the endothelium is important

Question 23

The rate limiting-step is the release of ____ since angiotensinogen is always present in plasma

Answer 23

renin

Question 24

Angiotensin 2 has what effect on the adrenal cortex and what does this lead to?

Answer 24

Angiotensin II stimulates the aldosterone-secreting cells in the zona glomerulosa of the adrenal cortex

The aldosterone passes in the blood to the kidney where it stimulates distal tubular Na+ ion reabsorption

Question 25

what controls the release of renin?

Answer 25

1.­ increased Renin release when P in afferent arteriole at the level of the JG cells decreases JG cells act as “renal baroreceptors”, less distension = increased­ secretion of renin. Intrinsic property, occurs if denervated 2. ­ increased sympathetic nerve activity causes increased renin release via b1 effect 3. Rate of renin secretion is inversely proportional to rate of delivery of NaCl at the macula densa (specialized distal tubule) decreased NaCl delivery = increased­ renin 4. Angiotensin II feeds back to inhibit renin 5. ADH inhibits renin release (osmolarity control)

Question 26

Close relationship between afferent arteriole with JG cells and macula densa provides mechanism for controlling input and output of tubules and basis of tubuloglomerular balance

Question 27

in hypovolaemia, how are volume deficits restored?

Answer 27

increased proximal AND distal tubule Na+ reabsorption together with osmotic equivalents of H2O, helps restore volume deficits, mediated by CV reflexes

Question 28

Angiotensin II is fundamentally important in the body’s response to hypovolaemia, why is this?

Answer 28

1. It stimulates aldosterone and therefore NaCl and H2O retention 2. It is a very potent biological vasoconstrictor, 4-8 x more potent than NE, therefore contributes to ­increased TPR 3. It acts on the hypothalamus to stimulate ADH secretion = increased­ H2O reabsorption from CD 4. It stimulates the thirst mechanism and the salt appetite (in the hypothalamus)

Question 29

describe the process of what would happen in the kidneys if there was an increase in volume

Answer 29

Question 30

Consider a person suffering from severe diarrhoea, who has lost 3l of salt and water (from ECF) and drinks 2 l of pure water There will be opposing inputs to ADH secreting cells, what are they

Answer 30

decrease ECF osmolarity = inhibition of ADH via osmoreceptors decrease ECF volume = increase ­ADH via baroreceptors

Question 31

Consider a person suffering from severe diarrhoea, who has lost 3l of salt and water (from ECF) and drinks 2l of pure water. There will be opposing inputs to ADH secreting cells: decrease ECF osmolarity = inhibition of ADH via osmoreceptors decrease ECF volume = increase ­ADH via baroreceptors what takes priority?

Answer 31

Volume considerations have primacy if ECV is compromised, so that ADH will increase ­because of the baroreceptors, even though this is associated with hypoosmolarity

Question 32

why does ECF volume take priority over ECF osmolarity?

Answer 32

Represents an “emergency” mechanism to save perfusion for the brain Normally, osmolarity is the main determinant of [ADH], but if sufficient volume change to compromise brain perfusion, then volume becomes the primary drive, so to conserve volume, tolerate disturbed osmolarity Once volume is restored in hypovolaemia, then osmolarity will be normalized and again becomes main determinant of ADH

Question 33

part 2

Question 34

Regulation of Na+ = Regulation of ECF \_\_\_\_\_\_

Answer 34

volume

Question 35

Aldosterone promotes Na+ reabsorption what promotes Na+ excretion?

Answer 35

ANP = Atrial Natriuretic Peptide promotes Na+ excretion

Question 36

If Aldosterone is given to normal subjects on an adequate Na+ diet, there will be Na+ ________ and K+ \_\_\_\_ There will be a weight gain of 2-3kg due to the Na+ and H2O retention After a couple of days, a spontaneous diuresis occurs 2° to _______ expansion, although K+ loss persists

Answer 36

retention loss volume

Question 37

what are all the effects of aldosterone?

Answer 37

increased Na+ reabsorption and increased K secretion both at the distal tubule increased weight because of retention of H2O with ­Na+ volume expansion stimulation of release of ANP from atrial cells = loss of Na+ and H2O ie Natriuresis BUT Aldosterone = continued K+ loss because still ­ K+ secretion as this is not counteracted by ANP

Question 38

ANP overrides aldosterone effects on Na+ reabsorption because of volume _______ = “Aldosterone escape”.

Answer 38

expansion

Question 39

What are the levels of sodium and potassium like in patients with Conns syndrome?

Answer 39

Similarly in patients with Conn’s syndrome, 1° hyperaldosteronism, due to a tumour of the adrenal cortex, they are K+ depleted, but not hypernatraemic ANP is secreted by atrial cells in response to expansion of ECF volume and causes natriuresis, loss of Na+ and H2O in urine Actions may be to inhibit secretion of renin, generally oppose the actions of angiotensin II

Question 40

In uncontrolled DM, where [BG] is not kept within strict control, the high plasma glucose level exceeds the maximum reabsorptive capacity in the proximal tubule therefore causing what?

Answer 40

Glucose remains in the tubule and exerts an osmotic effect to retain H2O in the tubule thereofre [Na+] in the lumen is decreased because the Na+ is present in a larger volume Since Na+ gains access to the proximal tubule cells by passive diffusion down a concentration gradient created by the active transport out of the basolateral surfaces, Na+ reabsorption will be decreased and therefore decreased ability to reabsorb glucose since it shares a symport with Na+

Question 41

how does uncontorlled DM affect the descending loop of henle?

Answer 41

In the descending limb of the loop of Henle, movement of H2O out of the tubule into the interstitium is reduced because the glucose and excess Na+ exert an osmotic effect to retain H20 therefore fluid in the descending limb is not so concentrated

Question 42

how does uncontorlled DM affect the ascending loop of henle?

Answer 42

Due to fluid in the descending limb being not so concentrated, this means that the fluid delivered to the ascending limb is less concentrated Since the NaCl pumps in ascending limb are gradient limited, medullary interstitial gradient is much less Therefore there is a considerable reduction in the volume of NaCl and H2O reabsorbed from the loops of Henle, so a large volume of NaCl and H2O is delivered to the distal tubule AND the interstitial gradient is gradually abolished

Question 43

Summary of the osmolarity in the different parts of the kidney Note the 200mOsmole gradient at each horizontal level of the ascending limb of the loop of Henle reflects the pumping of the active pumps

Answer 43

Question 44

Under normal conditions, a large volume of NaCl and H2O delivered to the distal tubule means there is excess ECF volume and therefore need to get rid of NaCl and H2O what would this cause?

Answer 44

The macula densa will detect the high rate of delivery of NaCl so that renin secretion will be suppressed and Therefore Na+ reabsorption at the distal tubule will be decreased normal reflex works in the wrong way and now the system works incorrectly Already have impaired reabsorption abilities now RAAS says just get rid of it Produces massive dehydration

Question 45

Summary of effects of uncontrolled diabetes normal on the left

Answer 45

Question 46

what is the urine like in patients with uncontrolled DM? and what is its effect?

Answer 46

A large volume of nearly isotonic urine will be excreted = decreased PV. The decreased PV will stimulate ADH release via baroreceptors but cannot be effective because the interstitial gradient has run down. Patients with uncontrolled DM can produce urine volumes of up to 6-8 l/day, causing severe salt and water depletion.

Question 47

what are someof the signs of DM?

Answer 47

If ingestion is not adequate, a raging thirst is one of the first signs of DM, then the hypotension may be so severe as to cause a hyperglycaemic coma This is due to inadequate BF to the brain whereas a hypoglycaemic coma is due to inadequate glucose for the brain

Question 48

Any solute which remains in the tubule can cause an osmotic diuresis eg NaCl or urea but this helps to eliminate their excess If we are secreting urea then the level of production of these in the body will reduce How is this different in DM?

Answer 48

Problem with DM is that the liver keeps producing glucose so the problem is not self-limiting

Question 49

The active transport mechanism that operates on the luminal surface of the thick ascending loop of Henle, actually involves __ ions as well as NaCl, ie Na+-\_\_-2Cl- co-transporter

Answer 49

K+ K+ This is a passive process, energy is provided by active transport, Na+/K+ATPase on the basolateral membrane Makes no difference to story, but important to know because loop diuretics can cause K+ ion wasting