Renal Physiology IV

Question 1

Elevations do not directly control BP but can raise BP

-more profound in some people than others

Answer 1

Na+

Question 2

In some individuals, increases in Na+ ingestion resets the renal function curve so that Na+ secretion is insufficient to maintain

Answer 2

Normal MAP

Question 3

The brain possesses an RAAS that is upregulated by (the opposite of what occurs with renal RAAS)

Answer 3

NaCl

Question 4

A modicum of Na+ (i.e. 1-3% of the remaining filtered load) can be reabsorbed by the

Answer 4

Collecting duct

Question 5

Most commonly occurs in the very young and elderly and sometimes develops as a complication of neurosurgery or traumatic brain injury

Answer 5

Hypernatremia

Question 6

Hypernatremia is caused by the disproportional loss in H2O relative to Na+ and/or hypertonic Na+ gain. It is defined as a plasma Na+ greater than

Answer 6

145 meq/L

Question 7

The signs and symptoms of hypernatremia reflect the hyperosmolality that leads to an impediment of

Answer 7

Neuronal structure and function (i.e. disrupted APs)

Question 8

In addition, the increased osmotic gradient present in hypernatremia favors the siphoning of intracellular fluid to the intravascular space. If severe enough, this can result in

Answer 8

Brain shrinkage resulting in cerebral bleeding and subarachnoid hemmorhage

Question 9

Therefore, patients with hypernatremia can present with signs and symptoms reflecting structural and functional insult to neuronal and muscular tissue including

Answer 9

Muscle weakness, lethargy, restlessness, and if severe enough, coma and death

Question 10

To treat hypernatremia, we have to carefully lower the

Answer 10

Hypertonicity

Question 11

Defined as a plasma Na+ of less than 136 meq/L

Answer 11

Hyponatremia

Question 12

In general, serum [Na+] of what concentration results in symptoms including: Lethargy, nausea, muscle weakness, irritability, and anorexia?

Answer 12

Less than 120 meq/L but greater than 110 meq/L

Question 13

As hyponatremia progresses, the change in the intra-versus extracellular osmotic gradients will favor the translocation of H2O into the

Answer 13

Intracellular space

Question 14

If profound enough, this translocation of H2O into the intracellular space will cause

Answer 14

Cellular swelling and damage

Question 15

IF not corrected will result in drowsiness, confusion, depressed reflexes, seizures, coma, and ultimately death

Answer 15

[Na+] below 110 meq/L

Question 16

Simply means that Na+ content has not changed and intravascular volume is fine. However, something has caused an inordinate amount of H2O retention leading to hyponatremia

Answer 16

Euvolemic hyponatremia

Question 17

In euvolemic hyponatremia, since volume status is within normal limits, we would not expect changes

Answer 17

Cardiovascular function

Question 18

Tachycardia, flat neck veins, and orthostatic hypotension are cardiovascular function changes associated with

Answer 18

Volume depletion

Question 19

Ascites and peripheral or pleural edema are cardiovascular changes associated with

Answer 19

Volume overload

Question 20

Some pathologies which can result in euvolemic hyonatremia include

Answer 20

Glucocorticoid deficiency, hypothyroidism, and SIADH

Question 21

Exerts negative feedbac on AVP, so deficiency can cause euvolemic hyponatremia

Answer 21

Cortisol

Question 22

Since euvolemic hyponatremia is due to some limitation in H2O excretion, we see an elevation in

Answer 22

Urine [Na+]

Question 23

Part of the treatment protocol in a euvolemic hyponatremic patient is

Answer 23

H2O restriction

Question 24

Results from a loss of total body water and Na+, whereby more Na+ is lost relative to H2O

Answer 24

Hypovolemic Hyponatremia

Question 25

What are three intrarenal causes of hypovolemic hyponatremia

Answer 25

1. ) Diuresis 2. ) Osmotic diuresis 3. ) Aldosterone deficiency

Question 26

What would the urine chemistry show in a patient with an intrarenal cause of hypovolemic hyponatremia?

Answer 26

Increased urine [Na+]

Question 27

Results from profound intravascular fluid loss such as that from diarrhea, vomiting, third space fluid shifts, and excessive sweating

Answer 27

Extrarenal hypovolemic hyponatresis

Question 28

What signs do we expect to see in a patient with hypovolemic hyponatremia from extrarenal causes?

Answer 28

Tachycardia, flattened neck veins, and orthostatic hypotension

Question 29

In an extrarenal cause of hypovolemic hyponatremia, what do we see in the urine chemistry?

Answer 29

Urine [Na+] is decreased and BUN is elevated (due to decreased renal perfusion)

Question 30

How can we treat the hypovolemic hyponatremic patient?

Answer 30

Give isotonic saline

Question 31

Results when an inordinate amount of H2O and some Na+ occurs such that plasma [Na+] is abnormally decreased

Answer 31

Hypervolemic hyponatremia

Question 32

Hypervolemic hyponatremia is also called

Answer 32

Dilutional hyponatremia

Question 33

One relatively common cause of hypervolemic hyponatremia is

Answer 33

Heart failure

Question 34

What would we expect to see in the urine chemisty of a patient in heart failure resulting in hypervolemic hyponatremia?

Answer 34

Decreased urine [Na+]

Question 35

Acute and chronic renal failure can also result in

Answer 35

Hypervolemic hyponatremia

Question 36

Why would acute and chronic renal failure result in hypervolemic hyponatremia?

Answer 36

Because GFR is decreased triggering the GFR decrease chain reaction

Question 37

What would we expect to see in the urine chemistry of a patient with hypervolemic hyponatremia due to acute or chronic renal failure?

Answer 37

Solute rich urine (i.e. increased urine [Na+]

Question 38

How would we treat hypervolemic hyponatremia, regardless of the cause?

Answer 38

Restriction of both Na+ and H2O

Question 39

In addition to causing hypertension, this condition is often characterized by hypokalemia, kaliuresis, metabolic acidosis, and decreased plasma [renin]

Answer 39

Mineralocorticoid hypertension

Question 40

Mineralocorticoid hypertension results in decreased

Answer 40

Plasma renin concentration

Question 41

A common cause of mineralocorticoid hypertension is a condition of

Answer 41

Aldosterone excess that hyperstimulates ENaC

Question 42

Can becaused by a primary or secondary hyperaldosteronism due to an aldosterone-secreting tumor, adrenal hyperplasia, or (rarely) adrenal carcinoma

Answer 42

Mineralocorticoid Hypertension

Question 43

Regardless of the specific cause, the mechanism for mineralocorticoid hypertension centers around heightened ENaC Na+ reabsorption at the expense of

Answer 43

Elevated K+ Excretion

Question 44

Aldosterone has been shown to induce the activation of several cell signaling mechanisms which are linked to inflammation and the development of

Answer 44

Fibrosis in cardiovascular tissues

Question 45

Fatal syndrome that will show in infants -Causes salt waisting

Answer 45

Type I hypoaldosteronism (pseudohypoaldosteronism)

Question 46

Type I hypoaldosteronism (pseudohypoaldosteronism) may stem from mutations in -The gene encoding ENaC protein

Answer 46

SCNN1

Question 47

A complex and mixed disorder that results from a disruption in the AVP system in which body H2O and often Na+ balances are severely disrupted

Answer 47

Diabetes Insipidus (DI)

Question 48

Caused by either a loss in AVP production or a mutation that disrupts the expression of V2R or AQP2

Answer 48

Diabetes insipidus (DI)

Question 49

Mutations which disrupt the expression of V2R or AQPs lead to a block in

Answer 49

AVP mediated H2O reabsorption within the tubules (nephrogenis)

Question 50

The AVP loss associated with DI can be either

Answer 50

Central or nephrogenic

Question 51

Under normal circumstances, promotes H2O reabsorption from the distal nephron and collecting ducts

Answer 51

AVP

Question 52

So what results then if AVP is lost?

Answer 52

Mass diuresis (polyuria) of dilute urine

Question 53

The formation of dilute urine is the hallmark of

Answer 53

DI

Question 54

The formation of solute rich urine is one of the hallmarks of

Answer 54

Diabetes Mellitus

Question 55

DI results in loss of ECF volume which will result in siphoning of H2O form plasma. The resulting reduced plasma volume stimulates Osmoreceptors that stimulate

Answer 55

Hypothalamic thirst centers

Question 56

Thus, many DI patients will also experience

Answer 56

Polydipsia (desire for increased fluid intake)

Question 57

The problem with this is that without AVP, all of the H2O that goes in, goes right out during urine. This is caused

Answer 57

Positive free H2O clearance

Question 58

Remember that any time there is a massive movement of H2O, what will likely follow?

Answer 58

Ions (Na+ and K+)

Question 59

Thus there is a high probability that DI patients will also present with one or more forms of

Answer 59

Ion imbalance

Question 60

Involves a problem with the AVP system such that improper free H2O balance occurs

Answer 60

Syndrome of Inappropriate ADH (SIADH) Secretion

Question 61

A defect at the level of hormone release is classified as

Answer 61

Neurogenic

Question 62

A defect in hormone responsiveness in the target tissue (nephron in this case) is classified as

Answer 62

Nephrogenic

Question 63

SIADH can be congenital or induced by a variety of stimuli including

Answer 63

Drugs, lesions, and neoplasms

Question 64

The congenital form of SIADH is present in the neonate and involves a mutation in the X-linked

Answer 64

V2 receptor (V2-R)

Question 65

This mutation is a gain of function mutation in which V2-R is constitutively activated in the absence of

Answer 65

AVP (Nephrogenic SIADH)

Question 66

In fact, these babies will most likely have undetectable levels of serum AVP, yet the mutant receptor maintians

Answer 66

AVP-like bioactivity

Question 67

Can assume one of several types which involve the inappropriate regulation of AVP secretion that results in erratic and unpredictable elevations in serum AVP

Answer 67

Induced SIADH

Question 68

Interestingly, patients with SIADH continue to drink despite the decreased

Answer 68

Free- H2O clearance and resultant hyponatremia

Question 69

Patients with SIADH can not excrete the proper free H2O load that is required to maintain normal

Answer 69

Plasma osmolality

Question 70

Part of the diagnostic criteria for SIADH

Answer 70

Euvolemia -many of these patients have euvolemic hyponatremia

Question 71

The underlying problem of the euvolemic hyponatremia in SIADH, and the condition that needs to be corected is the

Answer 71

Hyponatremia

Question 72

What are the 4 defining characteristics of SIADH?

Answer 72

1. ) Highly concentrated urine (osmolality greater than 100) 2. ) Urine Na+ greater than 40 meq/L 3. ) Euvolemic hyponatremia (serum Na+ below 136 meq/L) 4. ) Hypoosmolality

Question 73

All of the hallmarks of SIADH present with the

Answer 73

Exclusion of glucocorticoid and thyroid hormone deficiency

Question 74

What are 3 treatments of SIADH?

Answer 74

1. ) fluid limitation 2. ) Treatment with loop diuretic 3. ) Restoration of eunatremia

Question 75

Which two compounds can be used to treat the nephrogenic form of SIADH?

Answer 75

Democycline and lithium

Question 76

Target the signaling molecules that orchestrate the V2-R-mediated activation of AQP2

Answer 76

Demeclocycline and lithium

Question 77

The principle extracellular anion -Vital with Na+ in setting tonicity

Answer 77

Chloride (Cl-)

Question 78

Alterations in plasma Na+ and Cl- usually move in paralle and to the

Answer 78

Same degree

Question 79

What is the likely result of changes in plasma Cl- tht are opposite to those of Na+ or changes that are disproportionate in magnitude?

Answer 79

Acid-base disorder

Question 80

Unless specifically indicated otherwise, assume that Na+ movement means

Answer 80

NaCl movement

Question 81

Thus, like Na+, Cl- is overwhelmingly reabsorbed within the

Answer 81

Nephron

Question 82

Unlike with Na+, changes in chloremic state are not as associated with body fluid balance. However, elevated plasma Cl- can be induced by

Answer 82

Dehydration (as with Na+)

Question 83

However, hyperchloremia can also be induced as a compensatory mechanism during

Answer 83

Metabolic acidosis

Question 84

Hyperchloremic metabolic acidosis can be identified as

Answer 84

Normal AG metabolic acidosis

Question 85

When perturbations in plasma volume, pH, etc occur. the precedence is to restore the

Answer 85

Euvolemic State

Question 86

Describes the ability of the nephron to maintain an effective Na+ resorptive capacity in the face of changing tubular Na+ load

Answer 86

Glomerular-Tubule (GT) balance

Question 87

Through this mechanism, as more Na+ is filtered, comparably more Na+ will be reabsorbed

Answer 87

GT balance

Question 88

Changes in peritubular capillary oncotic and hydraulic pressures, alterations in the constituents of the filtrate, and the TGF system collectively provide the feedback that supports

Answer 88

GT balance

Question 89

An-II up-regulates Na+ conservation by stimulating Na+-H+ exchange within the

Answer 89

Proximal tubule

Question 90

This causes the reabsorption of Na+ and the secretion of

Answer 90

H+

Question 91

An-II also stimulates ENaC, thereby supporting Na+ reabsorption from the

Answer 91

Distal nephron

Question 92

Recall, AII induces aldosterone secretion. Aldosterone stimulates Na+ reabsorption from the

Answer 92

ASDN (and to a lesser degree from the collecting ducts)

Question 93

The trade-off for aldosterone directed Na+ reabsorption is an increase in the excretion of both

Answer 93

K+ and NH4+

Question 94

Increased renal SNS tone dampens

Answer 94

GFR and RBF

Question 95

SNS post-ganglionics also synapse within the JG | apparatus: norepi stimulates the RAS via

Answer 95

Type B1 adrenoreceptors

Question 96

What stimulates aldosterone secretion: 1. ) Directly 2. ) Indirectly

Answer 96

1. ) An-II | 2. ) SNS activity

Question 97

Activates α adrenoreceptors within the tubule epithelium

Answer 97

Norepinephrine

Question 98

These α adrenoreceptors are coupled to the activation of

Answer 98

Na+-H+ exchangers and Na+/K+ ATPases

Question 99

Thus the renal α adrenergic response induces

Answer 99

Na+ reabsorption and H+ secretion

Question 100

Impairs Na+ reabsorption -Secreted by atrial myocytes

Answer 100

Atrial Natriuretic Peptide (ANP)