Renal- Integration of salt and water balance

Question 1

What are the body fluid compartments in a 70kg average man

Answer 1

Total body water: 42kg
Intracellular: 28L
Extracellular: 14L

Interstitial: 11L
Intravascular: 3L

Question 2

Describe net water retention in vessels due to albumin

Answer 2

Albumin is not present in the extracellular fluid.

 Albumin contributes a major portion of the colloid
oncotic pressure.
 As blood pressure is necessary to keep blood flow
against the total peripheral resistance, there would
always be a bigger pressure inside vessels than in the surrounding tissues.
 Albumin and other protein, which are not able to permeate through the capillary wall offset this pressure excess inside
vessels to ensure that net filtration in the capillary bed is close to 0.
 This pressure equivalent is known as 𝛑 or colloid osmotic pressure.
 Any remaining net filtration is normally swept up by the lymphatic system.

Question 3

Describe how the ultimate goal of circulation is to support body metabolic goals

Answer 3

Baroreceptors both in the low and high pressure system signal to the brain.
 Short-term changes are signalled to effectors via the ANS: heart rate (inotropy) and vascular tone.
o Patient in shock: measure peripheral pulse. If no pulse, then measure pulse in a large vessel.
 Long-term changes are counter-regulated by altering NaCl excretion by the kidneys.
 Water retention regulated separately via osmolarity. However, if effective circulating volume is at stake, circulation takes
precedence over constant osmolarity. The body will give up the need to keep the osmolarity constant.

Question 4

What is the effective circulating volume and where is it measured

Answer 4

The effective circulating volume is a functional volume (a volume you cannot actually measure) which indicates fullness of
the circulation.
 Urinary Na
+ output is lower when standing but higher when immersed in warm water: hydrostatic pressure increases
venous return.
 Edematic states (e.g. congestive heart failure, nephrotic syndrome, hepatic cirrhosis): characterised by high extracellular
volume but low Na
+ excretion.
 Thoracic low pressure vessels seem to sense best the effective
circulating volume. They are isolated from pressure changes
because they are in the negative pressure of the thoracic
activity

Question 5

Describe some low and high pressure barosensors

Answer 5

Central vascular sensors:
o Low pressure sensors (very important):
 Cardiac atria
 Pulmonary vasculature
o High pressure sensors (less important):
 Carotid sinus
 Aortic arch
 Juxtaglomerular apparatus (renal afferent
arteriole)
 Sensors in the CNS (less important)
 Sensors in the liver (less important)

2. Signals
    Renin-angiotensin-aldosterone
    Increased sympathetic tone of kidney blood flow (reduced GFR and Na
   + excretion).
    ADH from the posterior pituitary (increased water retention in CCD).
    Decreased ANP from cardiac myocytes (reduced Na
   + excretion).

3. Redundancy
 Angiotensin II will constrict both efferent and afferent arterioles (keeping GFR constant while dramatically lowering renal
plasma flow) but also upregulates Na
\+/H
\+ exchange in the proximal tubule.

Question 6

Describe RAAS

Answer 6

Angiotensinogen is synthesised by the liver and released into systemic
circulation. The liver only contains small stores of angiotensinogen.
 Renin is produced by and stored in distinctive granules by the granular
cells of the renal juxtaglomerular apparatus.
 Decrease in effective circulating volume stimulates the release of
renin.

 Renin cleaves angiotensinogen into angiotensin I.
 Angiotensin-converting enzyme (ACE) cleaves the inactive angiotensin
I into the active angiotensin II. ACE is present on the luminal surface of
vascular endothelia throughout the body and is abundantly present in
the endothelium-rich lungs. ACE in the kidney, particularly in the
endothelial cells of the afferent and efferent arterioles can produce enough angiotensin II to exert local vascular effects.

Question 7

How is renin stimulated

Answer 7

↓ systemic blood pressure (sympathetic effect on the juxtaglomerular apparatus): a low effective circulating volume is
sensed by the baroreceptors in the central arterial circulations. This signals the medullary control centres to increase sympathetic outflow to the juxtoglomerular apparatus, thus increasing renin release.

 ↓ 𝐍𝐚𝐂𝐥 concentration at macula densa (NaCl sensor): ↓ effective circulating volume  ↓ GFR  ↓ luminal [NaCl] at the
macula densa  ↑ renn release.

 ↓ renal perfusion pressure (renal baroreceptor): stretch receptors in the granular cells of the afferent arterioles sense the
decreased distension associated with low effective circulating volume. The ↓ stretch lowers [Ca
2+]  ↑ renin release  ↑
blood pressure.

Question 8

What causes inhibition of renin release

Answer 8

Propranolol

 Increased distention (high extracellular volume)

Question 9

How can these regulatory mechanisms be disrupted

Answer 9

Hypertension due to mutated effectors: WNK1 and WNK4 mutations, Cullin-3 mutations, all over-activating NCC in the DCT
(Gordon’s syndrome).
 Reduced effective circulating volume: heart failure, severe haemorrhagic shock, hypovolemic shock, septic shock (all
vascular tone is lost).
 Hyperaldosteronism  chronic volume expansion  downregulation of ADH secretion  hypernatraemia (high Na
+ in the
blood).
 Pregnancy: left shift in threshold for ADH release. Decreased osmolarity by 8-10 mosm.
 Diuretic administration: the body normally accommodates itself for several days, causing a reduced loss of salts.
 Alcohol and other opiate antagonists inhibit ADH release, so lose too much water.