Flashcards in Renal Chapter 7: Control of Na/Water Excretion: Regulation of Plasma Volume Deck (80)
Is balance regulated based on input or consequences of input and loss?
What does control of salt and water excretion serve to do? Describe 3 things.
regulated in response to consequences of input and loss
consequences are primarily manifested through cardiovascular system
Control of salt and water excretion serves to (1)
maintain a body fluid volume appropriate for filling the vascular tree, (2) maintain
an osmolality of that fluid appropriate for the function of cells bathed in it, and (3)
allow the heart to generate the arterial pressure necessary to perfuse peripheral tissues.
In regulating total body salt and water, the kidneys are actually regulating 4 quantities simultaneously. Describe them.
1. water balance
2. salt balance
3. osmolality (not input output...its a ratio of substances: salt and water)
4. blood pressure
What are the effectors of the blood pressure regulation?
(Effectors change what they do in response to the signals in order to return bp to set-point)
1) heart (variable contractility and beat rate)
2) peripheral arterioles (det. resistance to flow in peripheral vasculature)
3) large veins (change their compliance to vary the capacity of the vascular system to hold blood)
4) kidneys (vary their output of salt/water)
What is the vasomotor center?
brainstem nuclei that control the set-point around which arterial bp is regulated
Describe the 2 major sets of detectors for short-term control of bp.
baroreceptors -afferent nerve cells (mechanoreceptors) with sensory endings in carotid arteries and arch of aorta
cardiopulmonary baroreceptors - nerve cells with sensory endings located in cardiac atria and parts of pulmonary vasculature (low-pressure baroreceptors bc assess pressures in regions of vascular tree where pressures are much lower than in arteries)
Describe the time span of arterial bp regulation. What is moment to moment regulation? How does regulation shift over time?
Figure 7-1 p 114
Time span of arterial blood pressure regulation. Moment-to-moment regulation
is purely cardiovascular in nature (although the renal vasculature is affected because it is part of the total peripheral resistance). Over time, control gradually shifts to renal processes, centered on renin-angiotensin systems (RAS) control of total peripheral resistance and excretion of sodium and water. Eventually, control is exerted chiefly by
regulating sodium and water excretion, with aldosterone as the central mediator.
Express mean arterial pressure as product of two factors.
MAP = CO x TPR (total peripheral resistance)
Changes in the activity of brainstem vasomotor center lead to changes in sympathetic signals that directly regulate...
cardiac contractility and HR
vasoconstriction or dilation of all systemic arterioles (incl. kidneys)
large peripheral veins (which contain 2/3 of total blood volume) when blood volume changes, almost all the change occurs in the volume of peripheral venous blood... compliance of veins (ease of being stretched) allows them to accommodate moderate changes in blood volume...their compliance can be regulated. (sym. signals can reduce compliance making veins less stretchy and so blood in veins squeezed and pressure raised.
Describe the effects of a pathological increase in venous compliance (as in certain forms of circulatory shock).
This will have the same effect as a major hemorrhage bc this creates an overcapacity of vascular system relative to its actual volume, with a resulting drop in central venous pressure and insufficient filling of cardiac chambers
Describe intrarenal baroreceptors.
they sense renal afferent arteriolar pressure (anatomically these are not neural baroreceptors, ie, they are not nerve cells and do not send signals to brainstem vasomotor center) ...they are specializations of cells of afferent arteriole:
granular cells (or juxtaglomerular cells) that form part of juxtaglomerular apparatus..
How are granular cells (acting as intrarenal baroreceptors) signaled/stimulated?
neural signals originating in the vasomotor center (generated in response to vascular basoreceptors) reach the granular cells via the renal sympathetic nerve.
-direct sensing of pressure in renal artery
-pressures sensed by neural baroreceptors elsewhere in the body
Describe the effects of arterial baroreceptors, cardiopulmonary baroreceptors, intrarenal baroreceptors. (What they act on and the effect)
Figure 7-2 p 116 or print out
What are the effects of angiotensin II?
its a potent vasoconstrictor and a mediator of multiple actions in the kidneys that affect sodium excretion
(affects bp directly as vasoconstrictor and indirectly via regulation of renal sodium excretion)
Describe the enzymes involved in the formation of angiotensin II
renin (comes from granular cells in kidney) acts on angiotensinogen (comes from liver) to produce a small (10 aa) product called angiotensin I... Angiotensin I is acted upon by another enzyme, (ACE), to produce the highly active (8 aa peptide) angiotensin II
Where is renin secreted? By what?
granular cells secrete renin
renin is secreted both into the interstitium of kidney and into lumen of afferent arterioles where it acts on circulating angiotensinogen to produce circulating angiotensin I.
Where is ACE expressed? What does it do?
expressed on luminal surface of epithelial cells in many parts of vasculature, particularly in lungs
converts angiotensin I to angiotensin II
What is the primary determinant of circulating levels of angiotensin II?
Circulating levels of angiotensinogen are usually fairly high and ACE activity
usually converts most angiotensin I into angiotensin II. Therefore, the primary
determinant of circulating levels of angiotensin II is the amount of renin available
to convert angiotensinogen to angiotensin I.
What determines how much renin is secreted?
(neural signals, afferent arteriolar pressure, and NaCl at the macula densa)
which produce signals via the renal sympathetic nerves that stimulate granular
cells: Activation of beta 1-adrenergic receptors on the granular cells stimulates renin
secretion via a cyclic adenosine monophosphate and protein kinase A-dependent process
intrarenal baroreceptors, ie, granular cells that deform in
response to changes in afferent arteriolar pressure; when the pressure falls, renin
granular cells act both as
detectors (of renal arteriolar pressure) and as signal generators (releasing renin)
in response to changes in pressure and sympathetic activity
Describe role of macula densa.
it measures the amount of
sodium chloride that leaves the thick ascending limb, directly bathing the macula
densa cells of the juxtaglomerular apparatus and delivered to the distal convoluted tubule. This amount of sodium chloride depends on both the rate of filtration and the rate of sodium reabsorption in all the nephron elements preceding the macula densa
when NaCl delivery increases, renin production decreases
(osmotic swelling causes release of transmitter agents that inhibit renin release)
Why is RAS a natural target for pharmacological intervention to reduce high blood pressure?
What components of the RAS system might drugs target?
Among the most significant actions of circulating
angiotensin II produced by the global RAS is general arteriolar vasoconstriction.
This vasoconstriction acts in parallel with sympathetically mediated neural
control. This raises total peripheral resistance, thereby increasing blood pressure.
A number of blood pressure–
lowering pharmacological agents are aimed at components of the RAS, including ACE inhibitors and blockers of the arteriolar smooth muscle receptors for angiotensin II
Describe the negative feedback of angiotensin II.
acts directly on granular cells (by interacting with AT1 receptors on granular cells) to increase intracellular Ca concentration, which inhibits renin production
most of time is its ok for vasoconstrictive and sodium retaining actions of angiotensin II to be exerted in parallel. However, by having both a global and an intrarenal RAS, it is possible to separate these actions so that changes in sodium excretion can be effected without altering vascular resistance elsewhere in body
What is responsible for determining the setpoint for mean blood pressure?
does this by controlling the amount of sodium and hence, volume, in the vascular space on a long-term basis.
Why doesn't ingesting a large amount of liquid or decreasing volume by sweating during a tennis match on a hot day cause immediate changes in bp?
Bc tendencies to change pressure are buffered immediately by the classic baroreceptor reflex and by renal output of salt and water
Draw a flow chart for how hemorrhage leads to changes in plasma angiotensin II concentration.
Draw for how hemorrhage is corrected for.
What does sodium have to do with blood pressure?
pressure in vascular tree require appropriate volume of blood (to fill highly elastic venous system and chambers of the heart)
blood pressure in long term dep. on blood volume. blood volume dep. on total ECF volume (plasma and interstitial spaces of tissues)
fluid in interstitial spaces acts as a buffer for plasma volume, protecting the vascular compartment from immediate changes associated with drinking, sweating and so on. (regulating ECF volume is crucial function of kidney...ECF volume must be normal for normal bp)
ECF volume det. by total osmotic content
(If the body regulates the total osmotic content of the ECF and regulates its osmolarity, it has accomplished the task of regulating its volume)
How can you estimate total ECF osmotic content?
total ECF osmotic content = sodium content x 2.
other 10% of ECF solute is accounted for by substances such as potassium, glucose, urea and so on
Describe sodium's effects on long term bp.
if body controls sodium content and plasma osmolarity (the water containing sodium), it controls volume, if it controls volume, it controls pressure.
How does excess sodium affect volume?
(excess sodium is almost always accompanied by water, so excess sodium causes an expansion of ECF volume)
What happens if there is no change in osmolaity?
What happens if there is excess sodium without excess water?
If there is no change in
osmolality, as shown in the middle example, the expansion is entirely
in the ECF and there is no change in ICF volume
If there is excess sodium
without excess water, as shown in the bottom example, water is drawn
from the ICF to maintain equal osmolalities between compartments
In both cases of
excess sodium, the increase in ECF volume causes an increase in both plasma and interstitial
See figure 7-8 page 124