Renal Chapter 7: Control of Na/Water Excretion: Regulation of Plasma Volume

Question 1

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.

Answer 1

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.

Question 2

In regulating total body salt and water, the kidneys are actually regulating 4 quantities simultaneously. Describe them.

Answer 2

1. water balance
2. salt balance
3. osmolality (not input output…its a ratio of substances: salt and water)
4. blood pressure

Question 3

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

Answer 3

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)

Question 4

What is the vasomotor center?

Answer 4

brainstem nuclei that control the set-point around which arterial bp is regulated

Question 5

Describe the 2 major sets of detectors for short-term control of bp.

Answer 5

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)

Question 6

Describe the time span of arterial bp regulation. What is moment to moment regulation? How does regulation shift over time?

Answer 6

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.

Question 7

Express mean arterial pressure as product of two factors.

Answer 7

MAP = CO x TPR (total peripheral resistance)

Question 8

Changes in the activity of brainstem vasomotor center lead to changes in sympathetic signals that directly regulate…

Answer 8

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.

Question 9

Describe the effects of a pathological increase in venous compliance (as in certain forms of circulatory shock).

Answer 9

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

Question 10

Describe intrarenal baroreceptors.

Answer 10

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..

Question 11

How are granular cells (acting as intrarenal baroreceptors) signaled/stimulated?

Answer 11

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

Question 12

Describe the effects of arterial baroreceptors, cardiopulmonary baroreceptors, intrarenal baroreceptors. (What they act on and the effect)

Answer 12

Figure 7-2 p 116 or print out

Question 13

What are the effects of angiotensin II?

Answer 13

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)

Question 14

Describe the enzymes involved in the formation of angiotensin II

Answer 14

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

Question 15

Where is renin secreted? By what?

Answer 15

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.

Question 16

Where is ACE expressed? What does it do?

Answer 16

expressed on luminal surface of epithelial cells in many parts of vasculature, particularly in lungs

converts angiotensin I to angiotensin II

Question 17

What is the primary determinant of circulating levels of angiotensin II?

Answer 17

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.

Question 18

What determines how much renin is secreted?

Answer 18

(neural signals, afferent arteriolar pressure, and NaCl at the macula densa)

neural baroreceptors,
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
production increases.

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

Question 19

Describe role of macula densa.

Answer 19

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)

Question 20

Why is RAS a natural target for pharmacological intervention to reduce high blood pressure?

What components of the RAS system might drugs target?

Answer 20

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

Question 21

Describe the negative feedback of angiotensin II.

Answer 21

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

Question 22

What is responsible for determining the setpoint for mean blood pressure?

Answer 22

the KIDNEY…

does this by controlling the amount of sodium and hence, volume, in the vascular space on a long-term basis.

Question 23

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?

Answer 23

Bc tendencies to change pressure are buffered immediately by the classic baroreceptor reflex and by renal output of salt and water

Question 24

Draw a flow chart for how hemorrhage leads to changes in plasma angiotensin II concentration.

Draw for how hemorrhage is corrected for.

Answer 24

Page 121

Page 122

Page 123

Question 25

What does sodium have to do with blood pressure?

Answer 25

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)

Question 26

How can you estimate total ECF osmotic content?

Answer 26

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

Question 27

Describe sodium’s effects on long term bp.

Answer 27

if body controls sodium content and plasma osmolarity (the water containing sodium), it controls volume, if it controls volume, it controls pressure.

Question 28

How does excess sodium affect volume?

Answer 28

(excess sodium is almost always accompanied by water, so excess sodium causes an expansion of ECF volume)

Question 29

What happens if there is no change in osmolaity?

What happens if there is excess sodium without excess water?

Answer 29

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
volumes

See figure 7-8 page 124

Question 30

How do kidney’s know about sodium content so that they can respond to changes?

Answer 30

pressures in various parts of the vascular
tree and in the kidneys

Pressure changes at any
of these sites are interpreted as a change in total body sodium because, except for pathophysiological circumstances, blood pressure, blood volume, and total body
sodium march in lockstep.

Question 31

How does GFR represent a mechanism for altering ECF volume?

Answer 31

a change in sodium filtered resulting from a change in GFR is also accompanied by a change in the amount of water filtered.

Question 32

Describe reflex control of GFR.

Draw flow charts for A) the effects of increased salt and water in ECF and B) increased salt in ECF.

Answer 32

reflex control of GFR is mediated by changing resistance of afferent and efferent arteriolar resistances. Changes in resistance are produced by changes in renal sym. nerve activity and circulating levels of (catecholamines?)

p 125

Question 33

How does high pressure affect levels of intrarenal angiotensin II in the intermediate response?

How are Na-H exchangers effected?

Answer 33

high pressure reduces a reduction in proximal tubular sodium reabsorption because of a reduction in the number
of functional transporters (Na-H antiporters) in the apical membrane of the proximal tubule epithelial cells. The reduction is probably in response to reduced levels of angiotensin II. There is also an increase (usually small) in glomerular filtration rate (GFR) and
an increase in peritubular hydrostatic pressure and renal interstitial pressure that favor reduced absorption of salt and water in the cortex (particularly from the proximal nephron).
ECF, extracellular fluid

levels of intrarenal angiotensin II.

Number of Na-H exchangers in apical membrane is strongly influenced by angiotensin II, when its levels fall, Na-H exchangers are withdrawn, along with a comcomitant reduction in activity of Na/K ATPase in BL membrane.

result of reduction in angiotensin II in response to high renal artery pressure is less Na absorption, and more presentation of sodium to loop of Henle and therefore more excretion..

See figure 7-10 p 126

Question 34

What happens if peritubular levels of angiotensin II are kept constant by experimental means?

Answer 34

then pressure natriuresis and diuresis are strongly blunted or even eliminated

A key feature of pressure natriuresis and diuresis is that the degree of salt and
water excretion for a given rise in pressure varies with the volume status of the
body.

Question 35

Describe how ECF volume affects pressure natriuresis when volume is high/low.

Answer 35

If the ECF volume is normal or high and the renal artery pressure rises, pressure natriuresis
and diuresis are very effective in increasing excretion of sodium and water and reducing blood volume. On the other hand, if ECF volume is low and the renal artery pressure rises, there is much less salt and water loss. It appears that the volume status of the body acts as a gain control on pressure natriuresis and diuresis. There is potent pressure natriuresis and diuresis when ECF volume is high, and much less pressure natriuresis and diuresis when ECF volume is depleted

Question 36

How/why does a rise in pertitubular capillary pressure affect net reabsorption?

Answer 36

reduces net reabsorption (and therefore causes more excretion)

Starling forces…high capillary pressure opposes reabsorption.

Question 37

High interstitial pressure should favor reabsorption, so why does it oppose it?

Answer 37

an increased interstitial
pressure causes back-leak of reabsorbed fluid from the interstitial space across the tight junctions into the tubule so pressure doesn’t alter cellular transport mechanisms for sodium and water but rather reduces the net reabsorption achieved by these mechanisms (particularly in the “leaky” proximal tubule)

In effect, if the interstitium gets “too full,” then it is difficult to transport more fluid into it. Put another way, high interstitial pressure does more to oppose the movement
of fluid from tubule to interstitium than it does to promote the movement
of fluid from interstitium to capillary

Question 38

How do changes in GFR cause changes in PPC and piPC?

Answer 38

PPC is set by (1) arterial pressure and (2) the combined vascular resistances of the
afferent and efferent arterioles, which determine how much of the arterial pressure is lost by the time the peritubular capillaries are reached. piPC is set by (1) arterial oncotic pressure and (2) filtration fraction (GFR/RPF), which determine
how much of the oncotic pressure increases from its original arterial value during
passage through the glomeruli.

Question 39

Fluid loss from the body end with 3 changes that affect GFR. Describe.

Answer 39

lower GFR

increased constriction of aff/eff arterioles (induced by renal nerves and angiotensin II)

decreased arterial hydraulic pressure

increased arterial oncotic pressure

Figure 7–10 illustrates how these same 3 factors also decrease renal interstitial hydraulic pressure and, hence, increase
sodium reabsorption. Thus, homeostatic responses that tend to lower GFR
in response to a reduction in body sodium also usually increase sodium reabsorption,
the “desired” homeostatic event of preserving volume in response to bodily
fluid depletion

Question 40

What happens with a high salt diet or expansion of the ECF volume?

Answer 40

1) decreased plasma oncotic pressure (resulting from dilution of plasma proteins)
2) increased renal arterial pressure
3) renal vasodilation secondary to decreased activity of the renal sympathetic nerves and decreased angiotensin II

(GFR increases a small amount and so does interstitial pressure which reduces fluid reabsorption)

Question 41

What is glomerulotubular balance?

Answer 41

in regulation of sodium excretion, control of tubular sodium reabsorption is more important than control of GFR.

(change in GFR automatically induces a proportional change in the reabsorption of sodium by the proximal tubules so that the fraction reabsorbed (but not amount) remains relatively constant.

(change in GFR still reflected as change in sodium and water presented to loop of Henle)

so when fraction reabsorbed is changed, the change is caused by processes other than changes in GFR.

128

mechanisms responsible for matching changes in tubular reabsorption to
changes in GFR are completely intrarenal (ie, glomerulotubular balance requires
no external neural or hormonal input;

Question 42

How do autoregulation and glomerulotubular balance work together?

Answer 42

autoregulation prevents GFR from changing too much in direct response to changes in bp

glomerulotubular balance blunts the sodium-excretion response to whatever changes in GFR does occur

Question 43

Where does independent control (when sodium ingestion and water ingestion both highly variable and unrelated to e/o… one in excess must be excreted more) take place?

Answer 43

most processes for independent control take place in distal nephron

Question 44

What does aldosterone do and what is the most important physiological factor controlling levels of aldosterone?

Answer 44

aldosterone -sodium retenton (vital in correcting long term changes in bp)

important controlling factor is circulating levels of angiontensin II

circulating angiotensin II will stimulate the adrenal cortex to
produce aldosterone.5 This targets the distal nephron to increase sodium reabsorption
and thus increase total body sodium and blood volume to produce a longterm
correction to total body sodium content and mean blood pressure

Question 45

Where does aldosterone stimulate sodium reabsorption?

Answer 45

mainly in the cortical connecting tubule and cortical collecting duct, specifically by principal cells.

fine-tuning (90% of sodium reabsorbed by this point)

2% of filtered sodium able to be controlled by aldosterone.

Question 46

Describe the mechanism of aldosterone’s action, receptors etc.

Answer 46

enough lipid character to freely cross principal cell membranes, then combines w receptors in cytoplasm

receptors undergo conformational change that revelas nuclear localization signal. receptor transported to nucleus, acts as a transcription factor that promotes gene expression and synthesis of messenger RNA (mRNA). The mRNA mediates the translation
of specific proteins. The effect of these proteins is to increase the activity or
number of luminal membrane sodium channels and basolateral membrane Na-KATPase
pumps to exactly supply what is needed to promote increased reabsorption
of sodium

figure 7-11 p 131

Question 47

What factors regulate aldosterone secretion?

Answer 47

angiotensin II
+
elevated plasma K conc. stimulates aldosterone secretion

atrial natriuretic factors inhibit secretion

Question 48

Describe prostaglandin activity.

Answer 48

Autoregulation of GFR involves local production of prostaglandins in conditions
when strong vasoconstriction might by itself reduce GFR and renal blood flow too much

intrarenal (autoregulatory) prostaglandin production opposes the actions of angiotensin II on the kidneys… prostaglandin prod. leads to vasodilation of arterioles and relaxation of mesangial cells

Increased local (intrarenal) angiotensin
II concentrations associated with renin release and increased sympathetic
input stimulate the production of prostaglandins.

Question 49

Draw a flow chart of a drop in blood pressure leading to tubular sodium reabsorption. Label where each even mainly takes place.

Answer 49

P 133

Question 50

Describe the vasodilatory effect of prostaglandins on angiotensin II and renal arterioles and blood flow and GFR.

Answer 50

vasodilatory effect of prostaglandins dampens the effect of angiotensin II and sympathetic input on renal arterioles and permits a reasonable, but reduced blood flow and GFR to continue

Question 51

The macula densa cells at the end of the thick ascending limb have Na-K-
2Cl symporters that can avidly take up Na, Cl, and K and cause the cells to swell dramatically when GFR (NaCl delivery) is high. Describe the mechanism.

Answer 51

The increased
Na and Cl in the lumen of the thick ascending limb stimulate the Na-H antiporter
and depolarizes the cells (as in thick ascending limb cells, the K recycles
via K channels). This depolarization leads to Ca entry across the basolateral membrane.
The rise in Ca leads to the release of ATP from the basolateral surface of the cells in close proximity to the glomerular mesangial cells. This ATP stimulates
purinergic P2 receptors on the mesangial cells and afferent arteriolar smooth
muscle cells. P2 receptor stimulation increases Ca in these cells and promotes
contraction. In addition, it is the increased Ca in the afferent arteriolar cells that
reduces renin secretion.

flow chart 7-13 p 134

Question 52

What is the effect of contraction of mesangial cells?

Answer 52

Contraction of mesangial cells decreases the effective filtration area, which decreases
GFR

Contraction of the afferent arteriolar smooth muscle cells increases
afferent resistance and decreases RBF and GFR

Question 53

Draw a flow chart for the mechanism of tubuloglomerular feedback.

Answer 53

Figure 7-14

p 135

Question 54

What are natriuretic peptides?
What is the source? Action? Promote what?

In what type of patients may these peptides be elevated?

Answer 54

they promote excretion of sodium in the urine

ANP (atrial)
BNP (brain)

main source of both natriuretic peptides is heart.

vascular and tubular actions- relax afferent arteriole, promoting increased filtration, and act at several sites in tubule. inhibit release of renin, inhibit the actions of angiotensin II that normally promote reabsorption of sodium and act in the medullary collecting duct to inhibit sodium absorption.

greatly elevated in patients w heart failure and serve as diagnostic indicators

Question 55

Describe the function of ADH. Where does it act? What stimulates its secretion?

Answer 55

major function of ADH is to increase permeability of cortical and medullary collecting ducts to water, therby decreasing excretion of water

in addition, ADH also increases sodium reab. by cortical collecting duct (same seg. influenced by aldosterone)

secretion of ADH (like aldosterone) are stimulated when plasma volume is reduced..they act together

Question 56

Which of the following hormones increase or decrease sodium reabsorption?

cortisol, parathyroid hormone, progesterone, glucagon, growth hormone, thyroid hormone, insulin

Answer 56

Cortisol, estrogen, growth hormone,
thyroid hormone, and insulin enhance sodium reabsorption,

glucagon,
progesterone, and parathyroid hormone decrease it

Question 57

What two variables of renal function control sodium excretion?

Answer 57

GFR and rate of sodium reabsorption

rate controlled by:
renin-angiotensin-aldosterone hormonal system, renal sympathetic
nerves, direct effects of arterial blood pressure on the kidneys (pressure natriuresis),
and atrial natriuretic factors

renal interstital hydraulic pressure and several renal paracrine agents

Question 58

In regards to mechanisms of sodium excretion, distinguish proxmial nephron mechanisms and distal nephron effects

Answer 58

(1) proximal nephron mechanisms (control of GFR, pressure natriuresis, and, to a lesser extent, changes in Starling forces) that lead to coupled changes in sodium and water excretion and

(2) distal nephron effects in which sodium can be reabsorbed independently of water. The proximal mechanisms are primarily involved in excreting excess ECF volume, whereas the distal mechanisms alter sodium excretion when ingestion of
sodium is not balanced by ingestion of water.

Both types of mechanisms can alter blood pressure because of the intimate relationship among total body sodium and
water, blood volume, and blood pressure.

Question 59

Water excretion conceptually consists of 2 major components. Describe them.

Answer 59

a proximal nephron component, in which water is absorbed along with sodium as an isotonic
fluid, and a distal nephron component, in which water can be reabsorbed independent of sodium.

The proximal nephron component is primarily a mechanism to regulate ECF volume in response to changes in blood pressure,

while the distal nephron rate of water reabsorption is independent of sodium reabsorption. It is determined mainly by ADH, which increases the water permeability of the collecting ducts, thereby increasing water reabsorption and, hence, decreasing water
excretion

Question 60

Describe where ADH is produced and where those cells are located. What are the most important inputs to those cells?

Answer 60

ADH is a peptide produced by a discrete group of hypothalamic neurons whose cell bodies are located in the supraoptic and paraventricular nuclei and whose axons
terminate in the posterior pituitary gland, from which ADH is released into
the blood. The most important of the inputs to these neurons are from cardiovascular
baroreceptors and osmoreceptors.

Question 61

What receptors initiate reflexes controlling ADH secretion? Why?

Where are they located?

Answer 61

under conditions of gain/loss of water without solute, osmoreceptors initiate reflexes that control ADH secretion

most osmoreceptors are located in tissues surrounding the 3rd cerebral ventricle

Question 62

Describe osmoreceptors. What do they signal? How?

Answer 62

in tissues surrounding the 3rd cerebral ventricle

these tissues contain fenestrated capillaries, which allow rapid adjustment of interstitial composition when plasma composition changes

Via these connections, an increase in osmolality stimulates them and increases their rate of ADH secretion

Question 63

What happens when a person drinks 1L of water?

Answer 63

excess water lowers body fluid osmolality which reflexively inhibits ADH secretion via hypothalamic osmoreceptors.

so water permeability of collecting ducts becomes very low, little or no water is reabsorbed from these segments and a large volume of extremely dilute urine is excreted

Question 64

What happens when baroreceptor and osmoreceptor inputs oppose each other (eg,
if plasma volume and osmolality are both decreased)?

Answer 64

In general, because of the
high sensitivity of the osmoreceptors, the osmoreceptor influence predominates
over that of the baroreceptor when changes in osmolality and plasma volume are
small to moderate.

However, a very large change in plasma volume will take precedence
over decreased body fluid osmolality in influencing ADH secretion; under
such conditions, water is retained in excess of solute, and the body fluids become
hypo-osmotic (for the same reason, plasma sodium concentration decreases

Question 65

What happens in diabetes insipidus?

Answer 65

Diabetes insipidus is characterized by a constant water diuresis, as
much as 25 L/day. In most cases, people with diabetes insipidus have lost the
ability to produce ADH because of damage to the hypothalamus or have lost the ability to respond to ADH because of defects in principal cell ADH receptors.
Thus, collecting-duct permeability to water is low and unchanging regardless of extracellular osmolality or volume.

Question 66

Where are the centers that mediate thirst located?

Answer 66

in hypothalamus

stimulated both by reduced plasma volume and by increased body fluid osmolality (same factors that stimulate ADH prod.)

angiotensin II can stimulate thirst by direct effect on brain

Question 67

Draw a flow chart summarizing the major factors that increase tubular sodium and water reabsorption in severe sweating.

Answer 67

Figure 7-17 p 143

Question 68

Describe inappropriate signaling to kidneys in congestive heart failure and result.

Answer 68

high levels of renin, angiotensin II, aldosterone, catecholamines, and other
mediators. Fluid volume is increased, leading to edema in the lungs, peripheral tissues, or both, which is why this is called congestive heart failure. Because of the high fluid volume, atrial pressures sensed by the cardiopulmonary baroreceptors are high. The high atrial pressures should lead to decreased ADH secretion and decreased sympathetic drive to the kidneys. Instead, these signals are increased,
and the kidneys operate at a new setpoint in which normal sodium excretion
only occurs at the expense of an excessive body fluid volume

Another characteristic of congestive heart failure is high levels of natriuretic
peptides. This is an appropriate response to the high atrial pressures and partially counteracts the sodium-retaining signals to the kidneys but does not restore sodium output to a level that would occur in a healthy person

Question 69

What is therapy for congestive heart failure?

Answer 69

Therapy for congestive heart failure includes
the use of diuretics to reduce the high fluid volume and drugs that inhibit the
generation of angiotensin II (ACE inhibitors) or block the actions of angiotensin
II (angiotensin receptor antagonists). In addition, synthetic natriuretic peptides
are becoming tools to promote diuresis.

Question 70

How can renal glomerular disease lead to increase in blood pressure?

Answer 70

renal glomerular disease often leads to inappropriate release of renin with subsequent increases in angiotensin II, aldosterone,
collecting-tubule sodium reabsorption, and finally an increase in blood
pressure;

Question 71

In a canine experiment, a dog’s filtered load of sodium in an isolated pump-perfused
kidney is found to be 15 mmol/min. (1) How much sodium do you predict
remains in the tubule at the end of the proximal tubule? (2) If its GFR is suddenly increased
by 33%, how much sodium now is left at the end of the proximal tubule?

Answer 71

(1) 5 mmol/min. Approximately two-thirds of filtered sodium is reabsorbed
by the proximal tubule. (2) 6.6 mmol/min. Filtered sodium rises
from 15 to 20 mmol/min. Glomerulotubular balance maintains fractional
sodium reabsorption at approximately two-thirds of the filtered
load.

Question 72

Normally aldosterone stimulates the reabsorption of approximately 33 g of sodium chloride/day. If a patient loses 100% of adrenal function, will 33 g of sodium chloride be excreted per day indefinitely?

Answer 72

The answer is no. As soon as the person starts to become sodium deficient
as a result of the increased sodium excretion, the usual sodiumretaining
reflexes will be set into motion. They will, of course, be unable
to raise aldosterone secretion, but they will lower GFR and alter the
other factors that influence tubular sodium reabsorption to compensate
at least partially for the decreased aldosterone-dependent sodium
reabsorption.

Question 73

A patient has suffered a severe hemorrhage and the plasma protein concentration
is normal. (Not enough time has elapsed for interstitial fluid to move into the
plasma.) Does this mean that the peritubular-capillary oncotic pressure is also
normal?

Answer 73

The answer is no. It will probably be slightly above normal because of
increased filtration fraction (ie, reduction in GFR and an even greater
reduction in renal blood flow secondary to renal arteriolar constriction
mediated by the renal sympathetic nerve and angiotensin II).

Question 74

If the right renal artery becomes abnormally constricted, what will happen to renin
secretion by the right kidney and the left kidney?

Answer 74

The right kidney will have increased secretion because of decreased renal
perfusion pressure acting via the intrarenal baroreceptor and decreased
flow to the macula densa. This increased secretion will result in elevated
systemic arterial angiotensin II and elevated arterial blood pressure,
both of which will inhibit renin secretion from the left kidney.

Question 75

A patient is suffering from primary hyperaldosteronism (ie, increased secretion of
aldosterone caused by an aldosterone-producing adrenal tumor). Is plasma renin concentration higher or lower than normal?

Answer 75

Plasma renin concentration is lower. The increased aldosterone causes the
body to retain sodium, which reflexively inhibits renin secretion. Thus,
one observes high plasma aldosterone and low plasma renin, a strong
tip-off to the presence of the disease because, in almost all other situations,
renin and aldosterone change in the same direction (because the rennin-
angiotensin system is the major control of aldosterone secretion

Question 76

An agent that increases sodium and water excretion is called a diuretic (even
though natriuretic is probably a better term). Block of sodium reabsorption in the
proximal tubule, loop of Henle, distal tubule, or collecting duct all exert a diuretic
effect. True or false?

Answer 76

The answer is true. Although some diuretic drugs are more potent than
others, blockage at any site results in at least mild diuresis. Because less
than 2% of the filtered load is normally excreted, it does not require a
huge reduction in the percentage reabsorbed to result in a large increase
in the amount of sodium that is excreted

Question 77

A person is given a drug that dilates both the afferent and efferent arterioles.
Assuming no other action of the drug, what will happen to the percentage of filtered
sodium that this person’s proximal tubule reabsorbs?

Answer 77

It will decrease. This question focuses on the effect of peritubular factors
on proximal sodium reabsorption. Although the GFR will remain
about the same, the renal blood flow increases. The peritubular capillary
pressure will, therefore, rise. At the same time, the peritubular oncotic
pressure will decrease because of the decreased filtration fraction. Both
of these effects tend to reduce fluid reabsorption from the interstitium,
which reduces proximal sodium and water reabsorption.

Question 78

A new drug is found to have dual actions: It blocks sodium entry pathways in the proximal tubule epithelium, and it binds to ADH receptors in the collecting ducts
and mimics the actions of ADH. Will the final urine contain excess or low amounts of sodium and excess or low amounts of water, and will it be hyperosmotic, isoosmotic,
or hypo-osmotic?

Answer 78

There will be excess sodium. We cannot be sure of the net effect on water
because there are opposing influences: the excess sodium leading to
increased water excretion and the ADH-like effect leading to decreased
water excretion. The osmolality, for sure, will be hyperosmotic.

Question 79

Another new drug also has dual actions, this time blocking sodium entry pathways
in the thick ascending limb and exerting ADH-like actions as in Question 7–8.

Now will the final urine contain excess or low amounts of sodium and excess or low
amounts of water, and will it be hyperosmotic, iso-osmotic, or hypo-osmotic?

Answer 79

There will be excess sodium, excess water, and an iso-osmotic urine.
Blocking sodium reabsorption in the thick ascending limb is what
“loop diuretics” do. Not only do they lead to excess sodium and water
in the urine, but they prevent the kidneys from generating a medullary
osmotic gradient. Even with the ADH-like actions of the drug,
the urine cannot become more concentrated than the now iso-osmotic
medullary interstitium.

Question 80

Angiotensin II that is capable of regulating the kidneys is formed by enzymatic action
in which locations (choose all that apply)?
A. The adrenal glands
B. The kidneys
C. The hypothalamus
D. The lungs

Answer 80

Both B and D are correct.