ECF Volume Regulation Flashcards
1
Q
What is the most important aspect of the ECF regulated by the kidney?
A
Its volume
2
Q
Why are body fluids in osmotic equilibrium?
A
Since H2O can move freely across all cell membranes
3
Q
What is the distribution of total body water between cells and ECF determined by?
A
The number of osmotically active particles in each compartment
4
Q
What are major ECF osmoles?
A
Na+ and Cl-
5
Q
What are the major ICF osmoles?
A
K+ salts
6
Q
What will regulation of Na+ indirectly regulate?
A
ECF
7
Q
What is the distribution of body water?
A
Plasma 3L
Interstitial fluid 11L
ICF 28L
Plasma + interstitial fluid = ECF = 14L
ECF = 1/3 ICF = 2/3
8
Q
What percentage of total body water do the ECF and ICF constitute?
A
60%
42L
9
Q
What will changes in the Na+ content of the ECF cause?
A
Changes in ECF volume and therefore affect the volume of blood perfusing the tissues, circulating volume and blood pressure
10
Q
What is regulation of Na+ basically dependent on?
A
High and low pressure baroreceptors
11
Q
What is the renal response to a decrease in ECF volume? (hypovolaemia)
A
Increased salt and water loss (isotonic fluid loss) e.g. vomiting, sweating
Reduced
- plasma volume
- venous pressure
- venous return
- atrial pressure
- end-diastolic volume
- stroke volume
- cardiac output
- blood pressure
- carotid sinus baroreceptor inhibition of sympathetic discharge
Increased
- sympathetic discharge
- systemic vasoconstriction
- total peripheral resistance and blood pressure towards normal
12
Q
What does increased sympathetic discharge cause?
A
Increased renal vasoconstriction and nerve activity
Increased renal arteriolar constriction and increase in renin
13
Q
What does increased renin result in?
A
Increased angiotensin II concentrations, decreased peritubular capillary hydrostatic pressure
Increased angiotensin II -> increased aldosterone -> increased distal tubule Na+ reabsorption and less Na+ excreted
14
Q
What does decreased peritubular capillary hydrostatic pressure cause?
A
Increased Na+ reabsorption from the proximal tubule, less Na+ excreted
15
Q
What are changes in proximal tubule Na+ reabsorption due to?
A
Changes in the rate of uptake by the peritubular capillaries, determined by IIp
16
Q
What is increase in Na+ reabsorption due to?
A
Greater reabsorptive forces in the peritubular capillaries
17
Q
When will Na+ reabsorption increase?
A
If NaCl and H2O have been lost, as onco-osmotic pressure will be increased more than normal, so up to 75% of the filtrate at the proximal tubule can be reabsorbed
18
Q
What is the reabsorptive range in the proximal tubule in volume excess and volume deficit?
A
65% in volume excess
75% in volume deficit
19
Q
How much filtrate can be reabsorbed in hypovolaemia compared to normovalaemia?
A
75% in hypovolaemia
70% in normovolaemia
20
Q
Why are plasma proteins diluted in hypervolaemia?
A
Ppc is greater than usual
Efferent arteriole is less constricted
Tlp is less than normal
21
Q
The vasoconstriction of afferent and efferent arterioles has little effect on GFR until what point?
A
Until the volume depletion is severe enough to cause a considerable drop in mean blood pressure
22
Q
What does the constriction of afferent arterioles due to sympathetic vasoconstriction, coupled with angiotensin II mediated constriction of the efferent arterioles maintain?
A
GFR
23
Q
Regulation of distal tubule Na+ reabsorption is under the control of what?
A
The adrenal cortical steroid hormone aldosterone - this is very important in the long-term regulation of Na+ and ECF volume
24
Q
What is aldosterone secretion controlled by?
A
Reflexes involving the kidneys themselves
25
Where is the smooth muscle of the media of the afferent arterioles specialised?
Just before they enter the glomerulus - contain large epithelial cells with lots of granules
26
How does the specialised smooth muscle of the media of the afferent arterioles work?
Works in conjunction with a histologically specialised loop of the distal tubule - the macula densa
The two together form the juxtaglomerular apparatus which acts as a sensor in the glomerulus and is involved in regulation of sodium and water reabsorption
27
What do juxtaglomerular cells produce?
Renin - a proteolytic enzyme (converts and activates other enzymes/hormones)
28
What does renin act on?
Angiotensin - a large protein in the alpha 2 globulin fraction of the plasma proteins
29
How does renin work?
Renin splits off the decapeptide angiotensin I (in the plasma) which is then converted by enzymes in the endothelium to the active octapeptide angiotensin II
30
What is the enzyme responsible for converting angiotensin I to angiotensin II?
Angiotensin converting enzyme
31
Where is angiotensin converting enzyme found?
Throughout the vascular endothelium
32
Where does the greatest proportion of conversion of angiotensin I to angiotensin II occur?
As the blood passes through the pulmonary circuit
33
What does angiotensin II stimulate?
The aldosterone-secreting cells in the zone glomerulosa of the adrenal cortex
34
What does aldosterone stimulate in the kidney?
Distal tubular Na+ reabsorption
35
What is the rate-limiting step determining the amount of angiotensin II?
The release of renin, since angiotensin is always present in the plasma
36
When is there increased renin release?
When pressure in the afferent arterioles at the level of the juxtaglomerular cells decreases
37
How do juxtaglomerular cells act as renal baroreceptors?
Less distension causes an increase in secretion of renin, this is an extrinsic property which works without innervation
38
Increased sympathetic nerve activity can cause increased renin release via what?
Beta 1 adrenergic receptors
39
The rate of renin secretion is inversely proportional to what?
To the rate of delivery of NaCl at the macula densa
| Decreased NaCl delivery causes increased renin secretion
40
What does angiotensin II feedback do?
Inhibits renin
41
Does ADH inhibit or stimulate renin release?
Inhibit
42
What provides the mechanism for controlling input and output of the tubules, and the basis of the tubuloglomerular balance?
The close relationship between the afferent arterioles, juxtaglomerular cells and macula densa
43
What effect do loop diuretics have on the kidneys?
They can cause K+ ion wasting
Act on the Na+ K+ 2Cl- symporter (co-transporter) in the ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption
This is achieved by competing for the Cl- binding site
44
What is water regulation controlled by?
ADH (vasopressin)
45
What is ADH?
Posterior pituitary hormone
| The cardinal hormone for water regulation, when present, water is reabsorbed
46
Where is ADH synthesised?
In the supraoptic and paraventricular nuclei of the hypothalamus in the brain
47
What is the half life of ADH?
| What does this allow?
Half-life around 10 minutes
| Allows it to be rapidly adjusted depending on the body's need for H2O conservation
48
What is the primary control of ADH secretion?
Plasma osmolarity
| Osmolarity increase means too little water, so ADH is produced to compensate
49
What happens when the effective OP of the plasma increases?
The rate of discharge of ADH secreting neurones in the SO and PVN nuclei is increased
This increases the release of ADH from the posterior pituitary
50
What are changes in neuronal discharge mediated by?
Osmoreceptors in the anterior hypothalamus, close to the SO and PVN nuclei
51
Where are the receptors which mediate thirst?
In the lateral hypothalamus
52
What do changes in the volume of the osmoreceptors result in?
Changes in osmoreceptor discharge, via stretch-sensitive ion channels
53
What happens when osmolarity increases?
H2O moves out of the cell
Volume of the cell shrinks and activates stretch-sensitive ion channels
Increased neural discharge
Increased ADH secretion
If the osmolarity decreases, the opposite occurs
54
What is normal plasma osmolarity?
280-290 mOsm/kg H2O
It is regulated very precisely
Small change in osmolarity can produce a large change in ADH secretion - very sensitive
55
What is an increase in osmolarity that does not cause an increase in tonicity ineffective in?
Ineffective in causing an increase in ADH concentration - only non-penetrating ions contribute to tonicity
56
What do solutes that can penetrate membranes move together with?
Water - they don't produce any osmotic drag or tonicity
57
What does the amount of urine produced depend on?
Both the ADH concentration and the amount of solute to be excreted
58
What effect does ingestion of hypertonic solutions (e.g. seawater) have?
Increases the solute load to be excreted and so increases urine flow, resulting in dehydration, as more H2O is required to excrete the solute load than that which was ingested
59
What is the site of water regulation?
The collecting duct, whose permeability is under the control of ADH
60
Whether or not the dilute urine is delivered to the distal tubule is concentrated and to what extent depends on what?
The absence or presence of ADH
61
How does ADH increase the permeability of the collecting ducts to H2O?
By incorporating H2O channels into the luminal membrane
62
What happens in the cortical collecting duct if ADH is present?
The cortical collecting duct becomes equilibrated with that of the cortical interstitium, it then passes through the hypertonic medullary interstitial gradient, created by the counter-current multiplier of the loop of Henle
63
What happens if maximum ADH is present?
The contents equilibrate with that of the medullary interstitium via osmotic efflux of H2O and so become highly concentrated at the tip of the medulla
Small volume of highly concentrated urine produced which contains relatively less of the filtered H20 than of the solute so compensates for the water deficit
This effectively adds pure H2O to the ECF
64
How is H2O reabsorbed?
By the oncotic pressure of the vasa recta, which will be greater than usual in the presence of H2O deficit
65
What happens in the absence of ADH?
Collecting ducts are impermeable to H2O so that the medullary interstitial gradient is ineffective in inducing H2O movements out of the collecting duct, so a large volume of dilute urine is excreted, compensating for H2O excess
66
What is the role of urea?
Plays an important part in the production of concentrated urine
67
What effect does movement of H2O out of the collecting ducts in the presence of ADH have on the urea remaining in the ducts?
Greatly concentrates the urea remaining in the ducts
68
What is the permeability of the collecting ducts to urea?
Relatively permeable, particularly towards the medullary tips
69
What happens as urea approaches the medullary tips?
There is increasing tendency for it to move down its concentration gradient
70
What enhances the permeability of the late medullary collecting duct to urea?
ADH
71
What happens to urea in antidiuresis with high levels of ADH?
Urea will be reabsorbed from the collecting duct into the interstitium, where it acts to reinforce the interstitial medullary gradient int he region of the thin ascending loops of Henle
72
Why is it important for urea to be reabsorbed?
If it remained in the tubule it would exert an osmotic effect to hold H2O in the tubule and so reduce the potential for rehydration
73
What is more important - conservation of H2O or the associated retention of urea?
Conservation of H2O
74
Why can collecting duct permeability be precisely graded to meet the demands of the body for H2O regulation?
Because any level of ADH between the extremes of maximum concentration and absence is possible
75
How does ECF volume affect ADH concentration?
Increased ECF volume - decreased ADH concentration
Decreased ECF volume - increased ADH concentration
76
What is the relationship between the rate of ADH secretion and the rate of discharge of stretch receptor afferents in the low and high pressure areas of the circulation?
Increase relationship
Decreased ECF volume causes decreased atrial receptor discharge causing increased ADH
77
Where are low pressure receptors located?
In the left and right atria and great veins
Sometimes called volume receptors
78
Where are high pressure receptors located?
Carotid and aortic arch baroreceptors
79
What do moderate decreases in ECF volume primarily affect?
The atrial receptors
80
How do atrial receptors normally work?
They exert tonic inhibitory discharge of ADH secreting neurones via the vague nerve
81
What happens if volume changes enough to affect mean blood pressure?
The carotid and aortic receptors will also contribute to changes in ADH secretion
82
What are responses graded in relation to?
The size of the perturbations
83
What are some of the other stimuli affecting ADH?
Pain, emotion, stress, exercise, nicotine and morphine all increase ADH
Following traumatic surgery, inappropriate ADH secretion occurs so H2O intake needs to be monitored
Alcohol suppresses ADH release so reduces [ADH]
84
What does aldosterone promote?
Na+ reabsorption
85
What does atrial natriuretic peptide promote?
Na+ excretion
86
What happens if aldosterone is given to normal subjects on an adequate Na+ diet?
There will be na+ retention and K+ loss, with a subsequent 2-3kg weight gain due to Na+ and H2O retention
After a couple of days, spontaneous diuresis occurs secondary to volume expansion, although K+ loss persists
87
What effect does aldosterone have on the distal tubule?
Aldosterone increases Na+ reabsorption and K+ secretion at the distal tubule
It also increases weight due to retention of H2O with increase Na+, causes volume expansion, stimulates release of ANP from atrial cells dn causes loss of Na+ and H2O
88
What does ANP override?
Aldosterone effects on Na+ reabsorption because of volume expansion
89
What is Conn's syndrome?
Primary hyperaldosteronism due to a tumour of the adrenal cortex
90
When is ANP secreted by atrial cells in patients with Conn's syndrome?
In response to expansion of ECF volume, causes natriuresis and loss of Na+ and H2O in urine
91
What effect does hypovolaemia have on proximal and distal tubule Na+ reabsorption?
Increased proximal and distal tubule Na+ reabsorption, followed by the osmotic equivalents of H2O - this helps to restore volume deficits
92
What hormone is fundamentally important in the body's response to hypovolaemia?
Angiotensin II
93
What does angiotensin II stimulate?
Aldosterone and therefore NaCl and H2O retention
94
How does angiotensin II contribute to the increase in TPR?
It is a very potent biological vasoconstrictor
95
What effect does angiotensin II have on the hypothalamus?
Acts on the hypothalamus to stimulate ADH secretion and increase H2O reabsorption from the collecting duct
Stimulates the thirst mechanism and the salt appetite
96
What does tubuloglomerular feedback contribute to?
GFR constancy
97
Normally osmolarity is the main determinant of [ADH], but if there is sufficient volume change to compromise brain perfusion, what becomes the primary drive?
Volume
98
When is it important to consider osmotic diuresis?
In terms of hypovolaemia - it illustrates how the renal function can be disrupted and is most important clinically in explaining the effects on uncontrolled diabetes mellitus in producing hyperglycaemic coma
99
What happens to the plasma glucose level in uncontrolled diabetes mellitus?
The high plasma glucose level exceeds the maximum resorptive capacity in the proximal tubule so glucose remains in the tubule and exerts an osmotic effect to retain H2O
Therefore, Na+ concentration in the lumen is decreased because the Na+ is present in a larger volume
100
What does decreased Na+ resorption result in for glucose reabsorption?
Results in a decreased ability to reabsorb glucose since it shares a symport with Na+
101
In diabetes, why is movement of H2O out of the tubule into the interstitium, in the descending limb of the loop of Henle, reduced?
Glucose and excess Na+ exert an osmotic effect to retain H2O, so fluid in the descending limb is less concentrated
102
What does it mean if fluid in the descending limb is less concentrated?
Fluid delivered to the ascending limb is less concentrated
103
Why is the medullary interstitial gradient much less?
Since the NaCl pumps in the ascending limb are gradient limited - there is therefore a considerable reduction in the volume of NaCl and H2O reabsorbed from the loops of Henle
104
How is the interstitial gradient gradually abolished?
As a large volume of NaCl and H2O is delivered to the distal tubule
105
What detects the high rate of delivery of NaCl so that renin secretion is suppressed and Na+ reabsorption at the distal tubule is decreased?
Macula densa
106
What happens when the medulla becomes isosmotic?
There is no driving force for water retention, so these systems are compromised
107
What does excretion of a large volume of nearly isotonic urine cause?
Decrease in plasma volume
108
What does decreased plasma volume stimulate?
ADH release via baroreceptors
109
What volume of urine can be produced by patients with uncontrolled diabetes mellitus?
Up to 6-8 l/day
110
If ingestion of water is not adequate, a raging thirst is one of the first signs of diabetes mellitus, and hypotension may be severe enough to cause what?
Hyperglycaemic coma due to inadequate blood flow to the brain
vs hypoglycaemic coma which is due to inadequate glucose supply to the brain
111
Any solute which remains in the tubule can cause what?
Osmotic diuresis
112
Why is osmotic diuresis not self-limiting in diabetes mellitus?
The liver keeps producing glucose
113
What provides the energy for the passive co-transporter?
Active transport of Na+/K+ ATPase on the basolateral membrane
