Control of body fluid osmolality and volume (berne Ch. 34)

Question 1

Neurons within the supraoptic and paraventricular nuclei synthesize either ADH or the related peptide oxytocin. ADH-secreting cells predominate in ______, whereas oxytocin-secreting neurons are primarily found ______

Answer 1

Supraoptic nucleus; paraventricular nucleus

Question 2

Secretion of ADH by the posterior pituitary can be influenced by several factors. The two primary physiological regulators of ADH secretion are:

Answer 2

1. Osmolality of the body fluids (osmotic) – most important

2. Volume and pressure of the vascular system (hemodynamic)

Question 3

The two primary physiological regulators of ADH secretion are osmolality of the body fluids (osmotic) and volume and pressure of the vascular system (hemodynamic). However, secretion of ADH by the posterior pituitary can be influenced by several other factors:
Stimulates:
Inhibits:

Answer 3

Stimulates: nausea, angiotensin II, bradykinin histamine and nicotine
Inhibits: atrial natriuretic peptide norepinephrine and ethanol

Question 4

Afferent fibers from the baroreceptors are carried in what nerves?

Answer 4

Vagus and glossopharyngeal nerves

Question 5

These are separate cells in the anterior hypothalamus that are exquisitely sensitive to changes in body fluid osmolality and therefore play an important role in regulating the secretion of ADH.

Answer 5

osmoreceptors

• *These cells behave as osmometers and sense changes in body fluid osmolality by either shrinking or swelling
• *The osmoreceptors respond only to solutes in plasma that are effective osmoles

Question 6

Urea is an (a) effective (b) ineffective osmole

Answer 6

b. ineffective

* * Thus, elevation of the plasma urea concentration alone has little effect on ADH secretion

Question 7

The set point of the system is the plasma osmolality value at which ADH secretion begins to increase. Below this set point, virtually no ADH is released. In healthy adults, it varies from:

Answer 7

275 to 290 mOsm/kg H2O

**pregnancy and low blood volume/pressure is associated with a decrease in the set point

Question 8

A decrease in blood volume or pressure (a) stimulates (b) inhibits secretion of ADH

Answer 8

a. stimulates

Question 9

What are the primary actions of ADH on the kidneys?

Answer 9

1. Increase the permeability of the collecting duct to water
2. Increase the permeability of the medullary portion of the collecting duct to urea
3. Stimulate reabsorption of NaCl by the thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct

Question 10

The actions of ADH on permeability of the collecting duct to water:

ADH binds to what receptor on the basolateral membrane of the cell?

Answer 10

V2 receptor (vasopressin 2 receptor)

Question 11

The actions of ADH on permeability of the collecting duct to water:

The binding of ADH to V2 receptor increases intracellular levels of (a) cAMP (b) cGMP (c) AMP (d) ATP

Answer 11

a. cAMP
* *V2 receptor (vasopressin 2 receptor) is coupled to adenylyl cyclase via a stimulatory G protein (Gs)
* *The rise in intracellular cAMP activates protein kinase A (PKA)

Question 12

The actions of ADH on permeability of the collecting duct to water:

The rise in intracellular cAMP activates protein kinase A (PKA). What is the effect of activated PKA in the apical membrane of the cell?

Answer 12

Insertion of vesicles containing aquaporin-2 (AQP2) water channels into the apical membrane of the cell, as well as the synthesis of more AQP2.

• *This shuttling of water channels into and out of the apical membrane provides a rapid mechanism for controlling permeability of the membrane to water.
• *The basolateral membrane is freely permeable to water as a result of the presence of AQP3 and AQP4 water channels

Question 13

When large volumes of water are ingested over an extended period expression of AQP2 and AQP3 in the collecting duct is (a) reduced (b) increased

Answer 13

a. reduced

* *These individuals cannot maximally concentrate their urine – diluted urine

Question 14

True or false

In states of restricted water ingestion, expression of AQP2 and AQP3 in the collecting duct increases

Answer 14

True – increase water reabsorption

**Thus, facilitates the excretion of maximally concentrated urine

Question 15

IN THE CLINIC

A term for excretion of large volumes of dilute urine

Answer 15

Polyuria

**To compensate for this loss of water, the individual must ingest large volumes of water (polydipsia)

Question 16

IN THE CLINIC
A condition wherein there is a decreased release of ADH from the posterior pituitary. This condition can be inherited or occurs more commonly after head trauma and with brain neoplasms or infections

Answer 16

Central diabetes insipidus or pituitary diabetes insipidus
**Individuals with central diabetes insipidus have a urine-concentrating defect that can be corrected by the administration of exogenous ADH

Question 17

IN THE CLINIC
A common clinical problem characterized by plasma ADH levels that are elevated above what would be expected on the basis of body fluid osmolality and blood volume and pressure

Answer 17

Syndrome of inappropriate ADH secretion (SIADH)

• *Individuals with SIADH retain water, and their body fluids become progressively hypoosmotic
• • SIADH can be caused by infections and neoplasms of the brain, drugs (e.g., antitumor drugs), pulmonary diseases and carcinoma of the lung

Question 18

IN THE CLINIC
These individuals have laboratory findings similar to those seen in SIADH, including reduced plasma osmolality, hyponatremia (reduced plasma [Na]), and urine more concentrated than would be expected from the reduced body fluid osmolality. However, unlike SIADH, where circulating levels of ADH are elevated and thus responsible for water retention by the kidneys, these individuals have undetectable levels of ADH in their plasma

Answer 18

Nephrogenic syndrome of inappropriate antidiuresis

Question 19

ADH increases the permeability of the terminal portion of the inner medullary collecting duct to urea. This results in an increase in reabsorption of urea and an increase in the osmolality of the medullary interstitial fluid. The apical membrane of the medullary collecting duct cells contains what transporters of urea?

Answer 19

UT-A1 and UT-A3

Question 20

ADH increases the permeability of the terminal portion of the inner medullary collecting duct to urea. This increase in permeability is associated with phosphorylation of _____

Answer 20

Phosphorylation of UT-A1 and UT-A3 through the cAMP/PKA cascade

Question 21

ADH stimulates reabsorption of NaCl by the thick ascending limb of Henle’s loop and by the distal tubule and cortical segment of the collecting duct. This increase in Na reabsorption is associated with increased abundance of key Na transporters:
Thick ascending limb of Henle’s loop:
Distal tubule:
Distal tubule and collecting duct:

Answer 21

Thick ascending limb of Henle’s loop: 1Na-1K-2Cl symporter
Distal tubule: Na-Cl symporter
Distal tubule and collecting duct: epithelial Na channel (ENaC)

Question 22

True or false

When body fluid osmolality is increased or blood volume or pressure is increased, the individual perceives thirst

Answer 22

False - blood volume or pressure is reduced

**Of these stimuli, hypertonicity is the more potent

Question 23

True or false

The thirst threshold is higher than the threshold for ADH secretion

Answer 23

True

• *On average, the threshold for ADH secretion is approximately 285 mOsm/kg H2O, whereas the thirst threshold is approximately 295 mOsm/kg H2O
• *Because of this difference, thirst is stimulated at a body fluid osmolality at which secretion of ADH is already maximal

Question 24

The neural centers involved in regulating water intake (the thirst center) are located in _____

Answer 24

Hypothalamus (subfornical organ)

Question 25

What is the difference between central and nephrogenic diabetes insipidus?

Answer 25

In central diabetes insipidus there is a decreased release of ADH from the posterior pituitary. In nephrogenic diabetes insipidus the collecting ducts do not respond normally to ADH

• • Many of the acquired forms of nephrogenic diabetes insipidus are the result of decreased expression of AQP2 in the collecting duct
• • Decreased expression of AQP2 has been documented in the urine-concentrating defects associated with hypokalemia, lithium ingestion, ureteral obstruction, a low-protein diet and hypercalcemia

Question 26

Maximally dilute urine

Answer 26

Uosm = 50 mOsm/kg H2O

Question 27

Maximum urine output per day

Answer 27

18 L/day

Question 28

Urine osmolality (Uosm)

Answer 28

Uosm = Solute excreted/Volume excreted

Question 29

This part of the loop of henle is the major site where solute and water are separated

Answer 29

Thick ascending limb

• *TAL is said to be the “diluting portion” of the nephron
• *TAL is impermeable to water

Question 30

The distal tubule and collecting duct also dilute the tubular fluid in what condition?

Answer 30

Absence of ADH
**The distal tubule and collecting duct is acted upon by ADH and thereby making them permeable to water – water reabsorption takes place

Question 31

Excretion of hyperosmotic urine involves removing water from the tubular fluid without solute. Because water movement is passive and driven by an osmotic gradient, the kidney must generate a hyperosmotic compartment that then reabsorbs water osmotically from the tubular fluid. What compartment in the kidney serves this function?

Answer 31

Interstitium of the renal medulla

*Thick ascending limb of the loop of henle is critical for generating the hyperosmotic medullary interstitium

Question 32

Mechanism for the excretion of dilute urine (water diuresis):

Fluid entering the descending thin limb of the loop of Henle from the proximal tubule is (a) isosmotic (b) hyperosmotic (c) hyposmotic with respect to plasma

Answer 32

a. Isosmotic

* * This reflects the essentially isosmotic nature of solute and water reabsorption in the proximal tubule

Question 33

Mechanism for the excretion of dilute urine (water diuresis):

True or false
Water is permeable in the descending thin limb of the loop of Henle

Answer 33

True
** The descending thin limb is highly permeable to water and MUCH LESS to solutes such as NaCl and urea (Urea is an ineffective osmole in many tissues, but it is an effective osmole in many portions of the nephron)

Question 34

Mechanism for the excretion of dilute urine (water diuresis):

As the fluid in the descending thin limb descends deeper into the hyperosmotic medulla, water is reabsorbed via what transport mechanism?

Answer 34

AQP 1

• *AQP 2, 3, 4, 6 and 8 are the predominant AQPs found in the collecting duct
• *AQP 1, 7 and 8 are found in the proximal tubule

Question 35

Mechanism for the excretion of dilute urine (water diuresis):

The ascending thin limb is impermeable to ____ but permeable to ______

Answer 35

Water; NaCl

• *As tubular fluid moves up the ascending limb, NaCl is passively reabsorbed because the concentration of NaCl in tubular fluid is higher than that in interstitial fluid
• *Thus, as fluid ascends through the thin ascending limb, it becomes less concentrated than the surrounding interstitial fluid

Question 36

Mechanism for the excretion of dilute urine (water diuresis):

The thick ascending limb of the loop of Henle is impermeable to (2) _____

Answer 36

Water and Urea

• *This portion of the nephron actively reabsorbs NaCl from tubular fluid and thereby dilutes it
• *Fluid leaving the thick ascending limb is hypoosmotic with respect to plasma

Question 37

Mechanism for the excretion of dilute urine (water diuresis):

IN THE ABSENCE OF ADH, The distal tubule and the cortical portion of the collecting duct are ____; IN THE ABSENCE OF ADH, The medullary collecting duct is ____

Answer 37

Impermeable to water (and urea); SLIGHTLY permeable to water and urea

Question 38

Mechanism for the excretion of concentrated urine (antidiuresis):

At what segment of the nephrom does urine concentration occur?

Answer 38

Collecting duct
**In the presence of ADH, which increases the permeability of the last half of the distal tubule and the collecting duct to water, water diffuses out of the tubule lumen, and tubule fluid osmolality increases. This diffusion of water out of the lumen of the collecting duct begins the process of urine concentration

Question 39

Mechanism for the excretion of concentrated urine (antidiuresis):

The maximum osmolality that the fluid in the distal tubule and cortical portion of the collecting duct can attain is approximately:

Answer 39

290 mOsm/kg H2O (the same as plasma)

Question 40

During antidiuresis, most of the water is reabsorbed in what segment of the nephron?

Answer 40

Distal tubule and cortical and outer medullary portions of the collecting duct
**Cortex > outer medulla > inner medulla

Question 41

Mechanism for the excretion of concentrated urine (antidiuresis):
An important point in understanding how concentrated urine is produced is to recognize that although reabsorption of NaCl by the ascending thin and thick limbs of the loop of Henle dilutes the tubular fluid, the reabsorbed NaCl accumulates in the medullary interstitium and raises the osmolality of this compartment Accumulation of NaCl in the medullary interstitium is crucial for the production of urine hyperosmotic to plasma because it provides the osmotic driving force for reabsorption of water by the medullary collecting duct. The overall process by which the loop of Henle, in particular, the thick ascending limb, generates the hyperosmotic medullary interstitial gradient is termed countercurrent multiplication

Answer 41

Not a question. IMPORTANT concept to understand

Question 42

Mechanism for the excretion of concentrated urine (antidiuresis):

The maximum osmolality that the fluid in the DISTAL TUBULE and CORTICAL PORTION of the COLLECTING DUCT attain is approximately
290 mOsm/kg H2O. Although the fluid at this point has the same osmolality as the fluid that entered the descending thin limb, its composition has been altered dramatically. Tubule fluid osmolality in this REGION reflects the presence of:

Answer 42

Urea and other solutes (K, NH4, and creatinine)

• *NaCl accounts for a much smaller proportion of total tubular fluid osmolality – because NaCl is absorbed in this region
• *High Urea content as compared to interstitial fluid – because this region is IMPERMEABLE to urea (no reabsorption takes place)

Question 43

Mechanism for the excretion of concentrated urine (antidiuresis):

The osmolality of the interstitial fluid in the medulla progressively increases from the junction between the renal cortex and medulla. The UREA content also varies along the length of the nephron:
DISTAL TUBULE and CORTICAL PORTION of the COLLECTING DUCT:
Medullary portion of the collecting duct:

Answer 43

DISTAL TUBULE and CORTICAL PORTION of the COLLECTING DUCT: High Urea content as compared to interstitial fluid
Medullary portion of the collecting duct: Urea content that is the same with medullary interstitium
**The equilibration of the urea content in the medullary portion is due to the reabsorption of the urea in the medullary collecting duct (in the presence of ADH, medullary duct is slightly permeable to UREA)

Question 44

The urine produced when ADH levels are elevated has an osmolality of ____

Answer 44

1200 mOsm/kg H2O and contains high concentrations of urea and other nonreabsorbed solutes
**Because urea in tubular fluid equilibrates with urea in the medullary interstitial fluid, its concentration in urine is similar to that in the interstitium. Urine volume under this condition can be as low as 0.5 L/day

Question 45

At the junction of the medulla with the cortex, interstitial fluid has an osmolality of approximately ____

Answer 45

300 mOsm/kg H2O with virtually all osmoles attributable to NaCl

Question 46

When dilute urine is produced, especially over extended periods, the osmolality of the MEDULLARY INTERSTITIUM declines. This reduced osmolality is almost entirely caused by a decrease in the concentration of _____

Answer 46

Urea
**This decrease reflects washout by the vasa recta and diffusion of urea from the interstitium into the tubular fluid within the medullary portion of the collecting duct

Question 47

When ADH levels are elevated (concentrated urine), the urea within the lumen of the medullary collecting duct and the interstitium equilibrates. The resultant concentration of urea in urine is equal to that in the medullary interstitium at the papilla, or approximately:

Answer 47

600 mOsm/kg H2O

Question 48

IN THE CLINIC

The vasa recta express what urea transporter?

Answer 48

UT-B urea transporter

**Individuals who lack this transporter have a decreased ability to concentrate their urine

Question 49

Any condition that reduces medullary interstitial osmolality impairs what function of the kidney?

Answer 49

Maximally concentrate urine

Question 50

True or false
It is the medullary interstitial urea concentration that is responsible for the reabsorption of water from the medullary collecting duct

Answer 50

False – NaCl
**The inner medullary collecting duct is highly permeable to urea; especially in the presence of ADH thus urea cannot drive water reabsorption across this nephron segment (urea is an ineffective osmole)

Question 51

The capillary networks that supply blood to the medulla, and are highly permeable to solute and water (water via AQP1)

Answer 51

Vasa recta

Question 52

Not only do the vasa recta bring nutrients and oxygen to the medullary nephron segments, but more importantly, they also remove the excess water and solute that is continuously being added to the medullary interstitium by these nephron segments. The ability of the vasa recta to maintain the medullary interstitial gradient is flow dependent. A substantial increase in vasa recta blood flow dissipates the medullary gradient

Answer 52

Not a question. IMPORTANT concept to understand

RECALL: A substantial increase in vasa recta blood flow (washout of osmoles from the medullary interstitium) is needed to maintain a low medullary interstitial gradient = diluted urine

Question 53

Provides a way to calculate the amount of solute-free water generated by the kidneys, either when dilute urine is excreted or when concentrated urine is formed

Answer 53

Free water clearance

Question 54

Osmolar clearance (Cosm)

Answer 54

(Uosm X V)/Posm

**clearance of total solute (osmoles, whether effective or ineffective) from plasma by the kidneys

Question 55

Free water clearance (CH2O)

Answer 55

CH2O = V – Cosm

Question 56

When dilute urine is produced, the value of CH2O is positive, which indicates that solute-free water is being excreted from the body. When concentrated urine is produced, the value of CH2O is negative, which indicates that solute-free water is being retained in the body

Answer 56

Not a question. IMPORTANT concept to understand

Question 57

What are the following factors necessary for the kidneys to excrete a maximal amount of solute-free water (CH2O)?

Answer 57

1. ADH must be absent. Without ADH, the collecting duct does not reabsorb a significant amount of water
2. The tubular structures that separate solute from water (ascending thin limb of Henle’s loop, thick ascending limb of Henle’s loop, distal tubule and collecting duct) must function normally
3. An adequate amount of tubular fluid must be delivered to the aforementioned nephron sites for maximal separation of solute and water. Factors that reduce delivery (e.g., decreased GFR or enhanced proximal tubule reabsorption) impair the kidneys’ ability to maximally excrete solute-free water

Question 58

What are the following factors necessary for the kidneys to conserve water maximally?

Answer 58

1. An adequate amount of tubular fluid must be delivered to the tubular structures that separate solute from water (ascending thin limb of Henle’s loop, thick ascending limb of Henle’s loop, distal tubule and collecting duct)
2. Reabsorption of NaCl by the nephron segments must be normal (the most important segment is the thick ascending limb of Henle’s loop)
3. A hyperosmotic medullary interstitium must be present (maintained via reabsorption of NaCl by the loop of henle and effective accumulation of urea)
4. Maximum levels of ADH must be present and the collecting duct must respond normally to ADH

Question 59

Principal factors regulating renal NaCl excretion:

Answer 59

Vascular volume, blood pressure, and cardiac output

Question 60

Guanylin is primarily produced in the ____ and uroguanylin is primarily producedin the ____

Answer 60

Proximal tubule; collecting duct

Question 61

Neuroendocrine cells in the intestine (primarily the jejunum) produce a peptide hormone in response to ingestion of NaCl

Answer 61

uroguanylin

• • A related peptide, guanylin, is also produced by the intestine (primarily the colon)
• *Both guanylin and uroguanylin are also produced by the nephron

Question 62

The actions of both uroguanylin and guanylin are mediated via activation of guanylyl cyclase and phospholipase A2. In the proximal tubule, guanylin and uroguanylin decrease the expression of Na,K-ATPase and inhibit the activity of the apical membrane Na-H antiporter. In the collecting duct these peptides inhibit the K channel (ROMK) in the apical membrane of the principal cells, which in turn indirectly inhibits reabsorption of Na by changing the driving force for entry of Na across the apical membrane.

Answer 62

Not a question. IMPORTANT concept to understand

Question 63

Refers to the portion of the ECF that is contained within the vascular system and is “effectively” perfusing the tissues (effective blood volume and effective arterial blood volume are other commonly used terms)

Answer 63

Effective circulating volume (ECV)

• *More specifically, ECV reflects the activity of volume sensors located in the vascular system
• *Unlike ECF, ECV is not a measurable and distinct body fluid compartment

Question 64

In a normal individual, changes in ECF volume result in parallel changes in vascular volume, blood pressure, and cardiac output. Thus, a decrease in ECF volume, a situation termed volume contraction, results in reduced vascular volume, blood pressure, and cardiac output. Conversely, an increase in ECF volume, a situation termed volume expansion, results in increased vascular volume, blood pressure, and cardiac output. When a person is in negative Nabalance, ECF volume is decreased and renal NaCl excretion is reduced. Conversely, with positive Na balance there is an increase in ECF volume, which results in enhanced renal NaCl excretion.

Answer 64

However, in some pathological conditions (e.g., congestive heart failure, hepatic cirrhosis), the renal excretion of NaCl does not reflect the ECF volume. In both these situations ECF volume is increased. However, instead of increased renal NaCl excretion, as would be expected, there is a reduction in the renal excretion of NaCl. To explain renal Nahandling in these situations, it is necessary to understand the concept of effective circulating volume (ECV)

Not a question. IMPORTANT concept to understand

Question 65

IN THE CLINIC
Patients with congestive heart failure frequently have an increase in ECF volume that is manifested as increased plasma volume and accumulation of interstitial fluid in the lungs (pulmonary edema) and peripheral tissues (generalized edema). This excess fluid is the result of NaCl and water retention by the kidneys. The kidneys’ response (i.e., retention of NaCl and water) is paradoxical because ECF volume is increased. However, this fluid is not in the vascular system but in the interstitial fluid compartment. In addition, blood pressure and cardiac output may be reduced because of poor cardiac performance. Therefore, the sensors located in the vascular system respond as they do in ECF volume contraction and cause retention of NaCl and water by the kidneys. In this situation, ECV, as monitored by volume sensors, is decreased.

Answer 65

REMEMBER

Question 66

IN THE CLINIC
Large volumes of fluid accumulate in the peritoneal cavity of patients with advanced hepatic cirrhosis. This fluid, called ascites, is a component of ECF and results from retention of NaCl and water by the kidneys. Again, the response of the kidneys in this situation seems paradoxical if only ECF volume is considered. With advanced hepatic cirrhosis, blood pools in the splanchnic circulation (i.e., the damaged liver impedes the drainage of blood from the splanchnic circulation via the portal vein). Thus, volume and pressure are reduced in the portions of the vascular system in which the sensors are found, but venous pressure in the portal system increases, which enhances fluid transudation into the peritoneal cavity. Hence, the kidneys respond as they would during ECF volume contraction: retention of NaCl and water and accumulation of ascites fluid. As with congestive heart failure, ECV in cirrhosis with ascites is decreased.

Answer 66

REMEMBER

Question 67

Vascular Low-Pressure Volume Sensors

Answer 67

Cardiac atria and pulmonary vasculature
**Because the low-pressure side of the circulatory system has high compliance, these sensors respond mainly to “fullness” of the vascular system

Question 68

Vascular High-Pressure Volume Sensors

Answer 68

Carotid sinus, aortic arch and juxtaglomerular apparatus of the kidney
** Of the two classes of baroreceptors, those on the high-pressure side of the vascular system appear to be more important in influencing sympathetic tone and ADH secretion

Question 69

With ECF volume contraction, activation of the low- and high-pressure vascular baroreceptors results in stimulation of sympathetic nerve activity, including fibers innervating the kidneys. This has the following effects:
The afferent and efferent arterioles are constricted, mediated by what type of receptors?

Answer 69

a-adrenergic receptors

• • This vasoconstriction decreases hydrostatic pressure within the glomerular capillary lumen, which results in a decrease in GFR
• *The effect of vasoconstriction is greater on the afferent arteriole

Question 70

With ECF volume contraction, activation of the low- and high-pressure vascular baroreceptors results in stimulation of sympathetic nerve activity, including fibers innervating the kidneys. This has the following effects:
Renin secretion is stimulated by cells of the afferent arterioles mediated by what type of receptors?

Answer 70

B-adrenergic receptors
**renin ultimately increases the circulating levels of angiotensin II and aldosterone, both of which stimulate Nareabsorption by the nephron

Question 71

With ECF volume contraction, activation of the low- and high-pressure vascular baroreceptors results in stimulation of sympathetic nerve activity, including fibers innervating the kidneys. This has the following effects:
Renin secretion is stimulated by cells of the afferent arterioles mediated by what type of receptors?

Answer 71

NaCl reabsorption along the nephron is directly
Stimulated mediated by what type of receptors?
a-adrenergic receptors
**Because of the large amount of Na+ reabsorbed by the proximal tubule, the effect of increased sympathetic nerve activity is quantitatively most important for this segment

Question 72

Site of synthesis, storage, and release of the proteolytic enzyme renin

Answer 72

Cells in the afferent arterioles (juxtaglomerular cells)

Question 73

What are the three factors that are important in stimulating renin secretion?

Answer 73

Perfusion pressure, sympathetic nerve activity and delivery of NaCl to the macula densa

Question 74

Renin is secreted by juxtaglomerular cells located in the afferent arteriole. At the cellular level, secretion of renin is mediated by the fusion of renin containing granules with the luminal membrane of the cell. This process is stimulated by a decrease in intracellular [Ca+ +], a response opposite that of most secretory cells, where secretion is stimulated by an increase in intracellular [Ca+ +]. It is also stimulated by an increase in intracellular [cAMP]. Thus, anything that increases intracellular [Ca+ +] will inhibit renin secretion. This would include stretch of the afferent arteriole (myogenic control of renin secretion), angiotensin II (i.e.,feedback inhibition), and endothelin. Conversely, anything that increases intracellular [cAMP] will stimulate renin secretion. This would include norepinephrine acting via β-adrenergic receptors and prostaglandin E2. Increases in intracellular [cGMP] have been shown to stimulate renin secretion in some situations and to inhibit secretion in others. Importantly, two substances that increase intracellular [cGMP] are ANP and nitric oxide. Both inhibit renin secretion

Answer 74

REMEMBER

Question 75

Angiotensin II has several important physiological functions:

Answer 75

1. Stimulation of aldosterone secretion by the adrenal cortex.
2. Arteriolar vasoconstriction, which increases blood pressure.
3. Stimulation of ADH secretion and thirst.
4. Enhancement of NaCl reabsorption by the proximal tubule, thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct.

Question 76

These segments are often referred to collectively as the aldosterone-sensitive distal nephron

Answer 76

Distal tubule and collecting duct

Question 77

Actions of aldosterone on Na reabsorption:

Answer 77

It increases the abundance of the apical membrane Na+-Cl− symporter in cells of the early portion of the distal tubule and the abundance of the Na+ channel (ENaC) in the apical membrane of principal cells in the late portion of the distal tubule and collecting duct (the activity of Na+ channels is also increased).
**ENaC is composed of three subunits (α, β, and γ). The α subunit is rate limiting for assembly. Thus, it is the abundance of this subunit that determines the amount of functional ENaC in the plasma membrane

Question 78

The heart produces two natriuretic peptides. Atrial myocytes primarily produce and store the peptide hormone ANP, and ventricular myocytes primarily produce and store BNP. Both peptides are secreted when the heart dilates (i.e., during volume expansion and with heart failure), and they act to relax vascular smooth muscle and promote excretion of NaCl and water by the kidneys. The kidneys also produce a related natriuretic peptide termed urodilatin. Its actions are limited to promoting NaCl excretion by the kidneys. In general, the actions of these natriuretic peptides, as they relate to renal NaCl and water excretion, antagonize those of the renin-angiotensin-aldosterone system.

Answer 78

Remember
Actions of natriuretic peptides
1. Vasodilation of the afferent and vasoconstriction of the efferent arterioles of the glomerulus. This increases GFR and the fi ltered load of Na+.
2. Inhibition of renin secretion by the afferent arterioles.
3. Inhibition of aldosterone secretion by the glomerulosa cells of the adrenal cortex.
4. Inhibition of NaCl reabsorption by the collecting duct, which is also caused in part by reduced levels of aldosterone. However, the natriuretic peptides also act directly on the collecting duct cells. Through the second messenger cGMP, natriuretic peptides inhibit cation channels in the apical membrane and thereby decrease reabsorption of Na+.
This effect occurs predominantly in the medullary portion of the collecting duct.
5. Inhibition of ADH secretion by the posterior pituitary and ADH action on the collecting duct. These effects decrease water reabsorption by the collecting duct and thus increase excretion of water in urine.

Question 79

The primary regulator of Na+ reabsorption by the distal tubule and collecting duct

Answer 79

Aldosterone

Question 80

Release of ANP and BNP from ____ ; Relase of urodilatin from ____

Answer 80

Heart; kidneys

**increase in Na secretion. Occurs during ECF expansion

Question 81

Sympathetic nerve fibers that innervate the
nephron segment (a) stimulates (b) inhibits reabsorption of Na

Answer 81

a. stimulates

Question 82

Directly stimulates reabsorption of Na+by the proximal tubule

Answer 82

Angiotensin II

Question 83

The renal response to ECF volume expansion involves the integrated action of all parts of the

nephron:
(1) The filtered load of Na+ is increased
(2) Reabsorption in the proximal tubule and loop of Henle is reduced (GFR is increased, whereas proximal reabsorption is decreased; thus, glomerulotubular balance does not occur under this condition)
(3) Delivery of Na+ to the distal tubule is increased. This increased delivery, along with the inhibition of reabsorption in the distal tubule and collecting duct, results in the excretion of a larger fraction of the filtered load of Na+ and thus restores euvolemia.

Answer 83

REMEMBER

Question 84

The nephron’s response to ECF volume contraction involves the integrated action of all its segments:

(1) The filtered load of Na+ is decreased
(2) Reabsorption by the proximal tubule and loop of Henle is enhanced (the GFR is decreased, whereas proximal reabsorption is increased; thus, glomerulotubular balance does not occur under this condition)
(3) Delivery of Na+ to the distal tubule is reduced. This decreased delivery, together with enhanced Na+ reabsorption by the distal tubule and collecting duct, virtually eliminates Na+ from the urine.

Answer 84

REMEMBER