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Flashcards in ECF Volume Regulation Deck (43):
1

What are the major ECF and ICF osmoles?

ECF - Na+ and Cl-

ICF - Potassium salts

2

What determines the regulation of ECF volume 

Regulation of ECF volume linked to regulation of body sodium

3

What is the division of total blody water?

2/3rds are found in intracellular fluid

1/3rd is extracellular

 

ECF is divided into interstitial fluid (majority) and plasma

4

What components of the body are involved in regulation of sodium?

Dependant on high and low pressure baroreceptors

5

What are the causes of reduced salt and H2O loss?

Vomitting

Diarrhoea 

Excess sweating 

(decrease in plasma volume, decrease in venous pressure, decrease in venous return, decrease in atrial pressure, decrease in end diastolic volume, decrease in stroke volume, decrase in cardiac output, decreases in carotid sinus baroreceptor inhibition of sympathetic discharge).

6

What is the effect of increased sympathetic discharge?

Increase in vasoconstriciton - increase in total peripheral resistance, increase in blood pressure - towards normal

7

What is the effect of increase in sympathetic discharge on the kidney?

Increase in renal vasoconstriction (renal arteriolar constriction increases) - increase in renin production

 

Renin leads to formation of angiotensin 2 - this decreases peritubular capillary hydrostatic pressure (increases oncotic pressure) - this causes sodium reabsorption from the proximal tubule - less sodium is excreted

Angiotension 2 causes an increase in aldosterone - increase in distal tubule sodium reabsorption - less sodium excreted

 

8

How does the reabsorption range change in times of volume excess compared to times of volume defecit?

Volume excess: reabsorption range is 65%

Volume defecit: reabsorption range is 75% (oncotic pressure is higher in the peritubular capillaries)

9

How does GFR change when volume changes?

GFR remains relatively unchanged - this is because of renal arteriolar constriction

 

Sympathetic vasoconstriction of afferent

Angiotensin 2 constricts the efferent

10

Where does aldosterone regulate sodium reabsorption?

Distal tubule

11

What are juxtaglomerular cells?

Specialized portion of the smooth muscle in the media of the afferent arteriole - contains large epithelial cells with plentiful granules

12

What are the juxtaglomerular cells associated with?

The macula densa (a specialised loop of the distal tubule)

13

Where is renin produced?

In the juxtaglomerular cells

14

What is renin?

A hormone 

Proteolytic enzyme 

Acts on angiotensinogen to produce angiotensin 1

15

Where is ACE found?

Vascular endothelium

The greatest conversion happens when the blood passes through the pulmonary circuit

Angiotensin 1 + ACE = Angiotensin 2

16

How does angiotensin 2 result in aldosterone release?

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

17

What is the rate limiting step in the RAAS pathway?

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

18

What controls the release of renin?

1.­ Pressure in afferent arteriole at the level of the JG cells falls

   JG cells act as “renal baroreceptors”

2. ­ Sympathetic nerve activity causes ­increase 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 - essentially a chemoreceptor) decrease in NaCl delivery = Increase in­ renin

4. Angiotensin II feeds back to inhibit renin.

5. ADH inhibits renin release (osmolarity control).

 

Angiotensin 2 and ADH provide feedback

19

What is the effect of angiotensin 2?

1. It stimulates aldosterone and \ NaCl and H2O retention.

2. It is a very potent biological vasoconstrictor, 4-8 x more potent than norepinephrine, \ contributes to ­ TPR

3. It acts on the hypothalamus to stimulate ADH secretion and increase in ­ H2O reabsorption from CD.

4. It stimulates the thirst mechanism and the salt appetite (in the hypothalamus).

20

What role does the macula densa have in decreasing GFR when the GFR is raised?

Flow through the tubule is increased

Flow past the macula densa increases

Paracrine from macula densa to afferent arterioles

Afferent arteriole constricts 

Resistance in afferent arteriole increases

Hydrostatic pressure in glomerulus decreases 

GFR decreases 

 

21

When a person has lost lots of water and salt (as a result of severe diarrhoea) how does the body respond?

ADH serves to increase water reabsorption (however this will effectively lower the already low blood osmolarity) but this is seen as beneficial regardless - normally osmolarity is the main determinant of ADH

Issues in volume take priority over issues in osmolarity - this is because there can be issues in brain perfusion if there is a loss in volume

22

When does ADH increase?

ECF osmolarity increase

ECF volume decrease

23

What is the solution to losses of salt and water?

Infuse or drink saline.

24

What is the effect of ANP on sodium excretion?

ANP promotes sodium excretion

25

What is the effect of aldosterone on potassium?

Causes potassium secretion

26

How is ANP linked to aldosterone?

Aldosterone causes sodium reabsorption 

Increase in weight because of retention of H2O with sodium reabsorption

 

Release of ANP from atrial cells

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

27

What are the imbalances in the blood present when the patient presents with conn's syndrome? - Hyperaldosteronism

Potassium is depleted but the patient is not hypernatraemic

 

ANP still works and causes loss of sodium in urine

28

What hormones does ANP have a controlling effect on?

Acts on the hypothalamus to reduce ADH secretion

Acts on the kidney to decrease the release of renin

Acts on the adrenal cortex to reduce the secretion of aldosterone

29

What is the effect of ANP on GFR?

Acts on the kidney - Increases GFR 

30

What organ does ANP act on to decrease blood pressure?

Medulla oblongata

31

What is the effect of elevated blood glucose levels on reabsorption in the proximal tubule?

Glucose remains in the tubule because the high plasma glucose exceeds the maximum reabsorptive capacity in the proximal tubule.

 

Glucose exerts an osmotic effect to retain H2O in the tubule 

32

How does the osmotic effect of glucose affect sodium reabsorption?

Glucose retains more H2O in the tubule 

Sodium is removed from the tubule by passive diffusion down a concentration gradient (created by the active transport out of the basolateral surfaces, sodium reabsorption will be decreased)

SInce there is water retention - the concentration of sodium is less and so less is reabsorbed by diffusion.

The ability to reabsorb glucose is reduced since it shares a symport with sodium

33

How does glucose retention in the descending limp of henle affect the movement of H2O?

Movement of H2O into the interstitium is reduced because of the glucose and sodium - retains H2O

 

Fluid in the descending limb is not so concentrated 

34

If water is not reabsorbed from the descending loops of henle, what is the effect on the ascending loops?

Since the NaCl pumps in ascending limb are gradient limited, medullary interstitial gradient is much less.

 

The increasing gradient of the interstitium is dependant on the increasing concentration of fluid from the descending limb to the ascending limb

 

There is considerable reduction in the volume of NaCl and H2O reabsorbed from the loops of henle

 

Large volumes of sodium chloride and H2O is delivered to the distal tubule

 

The interstitial gradient is gradually abolished

35

Here is a summary of the osmolarity in the different parts of the kidney

36

What is the effect of renin when levels of NaCl and H2O are increased?

Elevation of Na/Cl volume and H2O indicate that there is excess ECF volume - there is a ned to get rid of NaCl and H2O

 

Renin acts to increase blood pressure and reabsorb water and sodium

 

Therefore 

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.

37

What parts of the nephron are sodium chloride and water reabsorbed?

38

Where is reabsorption affected in diabetes?

39

What type of urine is excreted from diabetic patients?

A large volume of nearly isotonic urine will be excreted

 

This results in a decreased plasma volume

Patients with uncontrolled DM can produce urine volumes of up to 6-8 l/day, causing severe salt and water depletion.

 

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.

40

Why doesn't ADH work in diabetes?

It isn't effective because the interstitial gradient has run down

41

What is the difference between a hyperglycaemic coma and a hypoglycaemic come?

Hyperglycaemic come - inadequate blood flow to the brain - hypoglycaemic coma is due to inadequate glucose for the brain

42

Normally a solute in the tubule can cause osmotic diuresis to help eliminate their excess, why isn't the problem with glucose self-limiting?

The liver continues to produce glucose

43

Potassium is also involved