Renal Physiology IV Flashcards
Elevations do not directly control BP but can raise BP
-more profound in some people than others
Na+
In some individuals, increases in Na+ ingestion resets the renal function curve so that Na+ secretion is insufficient to maintain
Normal MAP
The brain possesses an RAAS that is upregulated by (the opposite of what occurs with renal RAAS)
NaCl
A modicum of Na+ (i.e. 1-3% of the remaining filtered load) can be reabsorbed by the
Collecting duct
Most commonly occurs in the very young and elderly and sometimes develops as a complication of neurosurgery or traumatic brain injury
Hypernatremia
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
145 meq/L
The signs and symptoms of hypernatremia reflect the hyperosmolality that leads to an impediment of
Neuronal structure and function (i.e. disrupted APs)
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
Brain shrinkage resulting in cerebral bleeding and subarachnoid hemmorhage
Therefore, patients with hypernatremia can present with signs and symptoms reflecting structural and functional insult to neuronal and muscular tissue including
Muscle weakness, lethargy, restlessness, and if severe enough, coma and death
To treat hypernatremia, we have to carefully lower the
Hypertonicity
Defined as a plasma Na+ of less than 136 meq/L
Hyponatremia
In general, serum [Na+] of what concentration results in symptoms including: Lethargy, nausea, muscle weakness, irritability, and anorexia?
Less than 120 meq/L but greater than 110 meq/L
As hyponatremia progresses, the change in the intra-versus extracellular osmotic gradients will favor the translocation of H2O into the
Intracellular space
If profound enough, this translocation of H2O into the intracellular space will cause
Cellular swelling and damage
IF not corrected will result in drowsiness, confusion, depressed reflexes, seizures, coma, and ultimately death
[Na+] below 110 meq/L
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
Euvolemic hyponatremia
In euvolemic hyponatremia, since volume status is within normal limits, we would not expect changes
Cardiovascular function
Tachycardia, flat neck veins, and orthostatic hypotension are cardiovascular function changes associated with
Volume depletion
Ascites and peripheral or pleural edema are cardiovascular changes associated with
Volume overload
Some pathologies which can result in euvolemic hyonatremia include
Glucocorticoid deficiency, hypothyroidism, and SIADH
Exerts negative feedbac on AVP, so deficiency can cause euvolemic hyponatremia
Cortisol
Since euvolemic hyponatremia is due to some limitation in H2O excretion, we see an elevation in
Urine [Na+]
Part of the treatment protocol in a euvolemic hyponatremic patient is
H2O restriction
Results from a loss of total body water and Na+, whereby more Na+ is lost relative to H2O
Hypovolemic Hyponatremia
What are three intrarenal causes of hypovolemic hyponatremia
- ) Diuresis
- ) Osmotic diuresis
- ) Aldosterone deficiency
What would the urine chemistry show in a patient with an intrarenal cause of hypovolemic hyponatremia?
Increased urine [Na+]
Results from profound intravascular fluid loss such as that from diarrhea, vomiting, third space fluid shifts, and excessive sweating
Extrarenal hypovolemic hyponatresis
What signs do we expect to see in a patient with hypovolemic hyponatremia from extrarenal causes?
Tachycardia, flattened neck veins, and orthostatic hypotension
In an extrarenal cause of hypovolemic hyponatremia, what do we see in the urine chemistry?
Urine [Na+] is decreased and BUN is elevated (due to decreased renal perfusion)
How can we treat the hypovolemic hyponatremic patient?
Give isotonic saline
Results when an inordinate amount of H2O and some Na+ occurs such that plasma [Na+] is abnormally decreased
Hypervolemic hyponatremia
Hypervolemic hyponatremia is also called
Dilutional hyponatremia
One relatively common cause of hypervolemic hyponatremia is
Heart failure
What would we expect to see in the urine chemisty of a patient in heart failure resulting in hypervolemic hyponatremia?
Decreased urine [Na+]
Acute and chronic renal failure can also result in
Hypervolemic hyponatremia
Why would acute and chronic renal failure result in hypervolemic hyponatremia?
Because GFR is decreased triggering the GFR decrease chain reaction
What would we expect to see in the urine chemistry of a patient with hypervolemic hyponatremia due to acute or chronic renal failure?
Solute rich urine (i.e. increased urine [Na+]
How would we treat hypervolemic hyponatremia, regardless of the cause?
Restriction of both Na+ and H2O
In addition to causing hypertension, this condition is often characterized by hypokalemia, kaliuresis, metabolic acidosis, and decreased plasma [renin]
Mineralocorticoid hypertension
Mineralocorticoid hypertension results in decreased
Plasma renin concentration
A common cause of mineralocorticoid hypertension is a condition of
Aldosterone excess that hyperstimulates ENaC
Can becaused by a primary or secondary hyperaldosteronism due to an aldosterone-secreting tumor, adrenal hyperplasia, or (rarely) adrenal carcinoma
Mineralocorticoid Hypertension
Regardless of the specific cause, the mechanism for mineralocorticoid hypertension centers around heightened ENaC Na+ reabsorption at the expense of
Elevated K+ Excretion
Aldosterone has been shown to induce the activation of several cell signaling mechanisms which are linked to inflammation and the development of
Fibrosis in cardiovascular tissues
Fatal syndrome that will show in infants
-Causes salt waisting
Type I hypoaldosteronism (pseudohypoaldosteronism)
Type I hypoaldosteronism (pseudohypoaldosteronism) may stem from mutations in
-The gene encoding ENaC protein
SCNN1
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
Diabetes Insipidus (DI)
Caused by either a loss in AVP production or a mutation that disrupts the expression of V2R or AQP2
Diabetes insipidus (DI)
Mutations which disrupt the expression of V2R or AQPs lead to a block in
AVP mediated H2O reabsorption within the tubules (nephrogenis)
The AVP loss associated with DI can be either
Central or nephrogenic
Under normal circumstances, promotes H2O reabsorption from the distal nephron and collecting ducts
AVP
So what results then if AVP is lost?
Mass diuresis (polyuria) of dilute urine
The formation of dilute urine is the hallmark of
DI
The formation of solute rich urine is one of the hallmarks of
Diabetes Mellitus
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
Hypothalamic thirst centers
Thus, many DI patients will also experience
Polydipsia (desire for increased fluid intake)
The problem with this is that without AVP, all of the H2O that goes in, goes right out during urine. This is caused
Positive free H2O clearance
Remember that any time there is a massive movement of H2O, what will likely follow?
Ions (Na+ and K+)
Thus there is a high probability that DI patients will also present with one or more forms of
Ion imbalance
Involves a problem with the AVP system such that improper free H2O balance occurs
Syndrome of Inappropriate ADH (SIADH) Secretion
A defect at the level of hormone release is classified as
Neurogenic
A defect in hormone responsiveness in the target tissue (nephron in this case) is classified as
Nephrogenic
SIADH can be congenital or induced by a variety of stimuli including
Drugs, lesions, and neoplasms
The congenital form of SIADH is present in the neonate and involves a mutation in the X-linked
V2 receptor (V2-R)
This mutation is a gain of function mutation in which V2-R is constitutively activated in the absence of
AVP (Nephrogenic SIADH)
In fact, these babies will most likely have undetectable levels of serum AVP, yet the mutant receptor maintians
AVP-like bioactivity
Can assume one of several types which involve the inappropriate regulation of AVP secretion that results in erratic and unpredictable elevations in serum AVP
Induced SIADH
Interestingly, patients with SIADH continue to drink despite the decreased
Free- H2O clearance and resultant hyponatremia
Patients with SIADH can not excrete the proper free H2O load that is required to maintain normal
Plasma osmolality
Part of the diagnostic criteria for SIADH
Euvolemia
-many of these patients have euvolemic hyponatremia
The underlying problem of the euvolemic hyponatremia in SIADH, and the condition that needs to be corected is the
Hyponatremia
What are the 4 defining characteristics of SIADH?
- ) Highly concentrated urine (osmolality greater than 100)
- ) Urine Na+ greater than 40 meq/L
- ) Euvolemic hyponatremia (serum Na+ below 136 meq/L)
- ) Hypoosmolality
All of the hallmarks of SIADH present with the
Exclusion of glucocorticoid and thyroid hormone deficiency
What are 3 treatments of SIADH?
- ) fluid limitation
- ) Treatment with loop diuretic
- ) Restoration of eunatremia
Which two compounds can be used to treat the nephrogenic form of SIADH?
Democycline and lithium
Target the signaling molecules that orchestrate the V2-R-mediated activation of AQP2
Demeclocycline and lithium
The principle extracellular anion
-Vital with Na+ in setting tonicity
Chloride (Cl-)
Alterations in plasma Na+ and Cl- usually move in paralle and to the
Same degree
What is the likely result of changes in plasma Cl- tht are opposite to those of Na+ or changes that are disproportionate in magnitude?
Acid-base disorder
Unless specifically indicated otherwise, assume that Na+ movement means
NaCl movement
Thus, like Na+, Cl- is overwhelmingly reabsorbed within the
Nephron
Unlike with Na+, changes in chloremic state are not as associated with body fluid balance. However, elevated plasma Cl- can be induced by
Dehydration (as with Na+)
However, hyperchloremia can also be induced as a compensatory mechanism during
Metabolic acidosis
Hyperchloremic metabolic acidosis can be identified as
Normal AG metabolic acidosis
When perturbations in plasma volume, pH, etc occur. the precedence is to restore the
Euvolemic State
Describes the ability of the nephron to maintain an effective Na+ resorptive capacity in the face of changing tubular Na+ load
Glomerular-Tubule (GT) balance
Through this mechanism, as more Na+ is filtered, comparably more Na+ will be reabsorbed
GT balance
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
GT balance
An-II up-regulates Na+ conservation by stimulating Na+-H+ exchange within the
Proximal tubule
This causes the reabsorption of Na+ and the secretion of
H+
An-II also stimulates ENaC, thereby supporting Na+ reabsorption from the
Distal nephron
Recall, AII induces aldosterone secretion. Aldosterone stimulates Na+ reabsorption from the
ASDN (and to a lesser degree from the collecting ducts)
The trade-off for aldosterone directed Na+ reabsorption is an increase in the excretion of both
K+ and NH4+
Increased renal SNS tone dampens
GFR and RBF
SNS post-ganglionics also synapse within the JG
apparatus: norepi stimulates the RAS via
Type B1 adrenoreceptors
What stimulates aldosterone secretion:
- ) Directly
- ) Indirectly
- ) An-II
2. ) SNS activity
Activates α adrenoreceptors within the tubule epithelium
Norepinephrine
These α adrenoreceptors are coupled to the activation of
Na+-H+ exchangers and Na+/K+ ATPases
Thus the renal α adrenergic response induces
Na+ reabsorption and H+ secretion
Impairs Na+ reabsorption
-Secreted by atrial myocytes
Atrial Natriuretic Peptide (ANP)
