Term
| How is total body water distributed? |
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Definition
1) 2/3 is Extracellular (Na+ is an extracellular ion)
- 3/4 of this is interstitial
- 1/4 is intravascular
2) 1/3 is Intracellular (K+ is principle cation) |
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Term
| What clinical scenarios often involve loss of na/water (volume depletion)? |
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Definition
Remember, losses are from EC compartment
1) GI losses- vomiting, diarrhea, hemmorhage
2) Renal losses- diuretics, osmotic diuresis
3) Skin/respiratory- fever, excessive sweating, burns
4) Other- bleeding, pancreatitis |
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Term
| Why might a patient present with hypotension, dizziness, orthostatic hypotension, tachycardia and low JVP? |
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Definition
Low intravascular volume
Tachycardia is reflex. |
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Term
| Why might a patient present with poor skin turgor (tenting of skin) and dry mucous membranes? |
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Definition
| Volume reduction in interstitial space (3/4 of EC volume) |
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Term
| What systems are in place to compensate for EC fluid loss? |
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Definition
1) RAAS- sodium and water retention in kidney
2) SNS- blood vessel constriction and cardiac contractility |
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Term
| What hormonal regulators will come into play when there is decreased NaCl delivery sensed by the macula densa? |
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Definition
1) Renin release
2) Aldosterone secretion
3) Renal reabsorption of sodium and expansion of EC space.
4) SNS activation
5) Baroreceptor-mediated ADH release |
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Term
| What are the principle hormonal regulators involved in the physiological respond to hypovolemia? |
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Definition
Low EC volume
1) Angiotensin II causes
- systemic vasoconstriction
- aldosterone release from adrenal gland
- constriction of efferent arterioles to maintain GFR.
** IF SEVERE, PGE won't be able to keep afferent arteriole open and GFR will be dominated by ANGII and fail.
2) Aldosterone (response to ang-II)
- Activates Na/Cl co-transporter, and the ENaC channel and basolateral Na/K ATPase in the distal tubule and collecting duct.
3) ADH
- released from posterior pituitary in response to increased plasma osmolarity or decreased volume/pressure (baroreceptors in carotid sinus)
- Increases water re-absorption in collecting duct (primary)
- Increases sodium retention by activating Na/K/2CL co-transporter in TAL and ENaC in collecting duct (secondary) |
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Term
| What are the primary and secondary actions of ADH in volume-depleted states? |
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Definition
Released from posterior pituitary in response to increased plasma osmolarity (primarily) or decreased volume/pressure (baroreceptors in carotid sinus)
1) Increases water re-absorption in collecting duct (primary)
2) Increases sodium retention by activating Na/K/2CL co-transporter in TAL and ENaC in collecting duct (secondary) |
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Term
| How do you go about treating disorders of volume depletion? |
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Definition
Expand that IV space
1) IV fluids (isotonic saline)
2) Treat etiology |
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Term
What are each of the following RARE inherited disorders of renal Na loss?
1) Bartter Syndrome
2) Gitelman Syndrome
3) Pseudohypoaldosteronism Type 1 |
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Definition
1) Defect in TAL causes a "loop-diuretic" like effect
- Loss of Na,K,2Cl transporter, ROMK channel or basolateral Cl channel
2) Defect in early distal tubule causes a "thiazide-like" effect
- Na Cl Co-transporter NCC channel LOF
3) AR defect in late distal tubule (like taking a potassium sparing diuretic like Amiloride)
- ENaC or mineralcorticoid receptor issue
- Channels are unresponsive to aldosterone |
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Term
| What defect might a mutation in the ROMK channel produce? |
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Definition
ROMK is important for potassium recycling in the TAL of henle, driving paracellular cation transport.
Mutations in ROMK (As well as Na/K/2Cl co-transporter) produce Bartter Syndrome, which presents as if the patient was taking a "loop diuretic" |
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Term
| What clinical symptoms might a patient with a mutation in the Na,K,2Cl transporter present with? |
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Definition
This transporter is critical for sodium reabsorption in the TAL of henle, and mutations are associated with Bartter Syndrome (Early childhood onset)
1) Low-normal EC volume
2) Low-normal BP
3) Elevated renin and aldosterone
4) Low potassium |
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Term
| What clinical symptoms might a patient with a mutation in the ENaC channel present with? |
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Definition
This transporter is important for sodium reabsorption in the late distal convoluted tubule and mutations might cause effects similar to taking a potassium-sparing diuretic like Amiloride.
Produces Pseudohypoaldosteronism Type 1, which is a AR disorder with
1) Volume depletion
2) Hypotension
3) Hyperkalemia despite elevated plasma aldosterone (channels are not sensitive!) |
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Term
| What clinical symptoms might a patient with a mutation in the Na, Cl co-transporter present with? |
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Definition
The NCC channel is a neutral symporter that is important for sodium reabsorption in the early distal convoluted tubule and mutations will produce symptoms similar to those of a patient on a Thiazide diuretic.
It is called GITELMAN's SYNDROME and presents with
1) Low-normal ECF volume
2) Low-normal BP
3) Elevated renin and aldosterone levels
4) Low potassium
5) Hypocalciuria |
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Term
| How do the clinical presentations of Bartter Syndrome and Gitelman's Syndrome compare? |
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Definition
They are the same, except Gitelman's also presents with Hypocalciuria.
Remember, Bartter (Loop diuretic like) is issue with Na,K,2Cl transporter in TAL and Gitelman's (Thiazide-like) is NCC channel issue in the early distal tubule.
Both present with
1) Low-normal ECF volume
2) Low-normal BP
3) Elevated renin/aldosterone
4) Low potassium |
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Term
| What are the most common clinical presentations of volume overload? |
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Definition
1) Advanced renal failure
2) Heart failure
3) Liver failure
4) Nephrotic syndrome |
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Term
What are the clinical signs/symptoms over increased Na/water in the IT space?
What about the IV space? |
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Definition
1) IT
- Pulmonary edema leading to dyspnea
- Lower extremity edema
- Ascites or abdominal distension
2) IV
- HTN |
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Term
| What factors drive the formation of Edema? |
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Definition
1) Renal Na/Water retention
2) Change in capillary starling forces |
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Term
| What is decreased "effective" arterial volume and in what clinical syndromes does it manifest? |
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Definition
Increased EC fluid volume AND under-filling of arterial bed
""The cells don't want it and the vessels don't either**
1) CHF
2) Cirrhosis
3) Nephrotic syndrome |
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Term
| Why is "effective circulating volume" low in CHF? |
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Definition
Remember, this is the volume essential to perfuse vital organs
1) Low CO leads to decreased pressure at baroreceptors
2) Decreased baroreceptor activation leads to sympathetic vasoconstriction and decreased blood flow to the kidneys
3) The kidneys sense low blood flow and respond with RAAS and ADH response |
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Term
| Why can you see volume overload in liver failure? |
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Definition
Decreased systemic vascular resistance, increased hepatic sinusoidal pressure and Hyoalbuminemia all can cause this.
1) Decreased systemic vascular resistance/splanchnic vasodilation leads to decreased "effective circulating volume," which causes increase in SNS tone and RAAS and ultimately leads to sodium retention by kidney.
2) Increased hepatic sinusodal pressure leads to increase in capillary hydrostatic pressure leading to ascites.
3) Hypoalbuminemia leads to decreased capillary oncotic pressure, which causes edema |
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Term
| Why can you see volume overload in Nephrotic syndrome? |
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Definition
Renal disorder defined by 1) Glomerular leak of protein and 2) loss of protein/albumin in urine
1) Hypoalbuminemia leads to decreased capillary hydrostatic pressure and ultimately to edema
2) Kidney responds to filtration leak by ramping up sodium retention. |
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Term
| How can you most effectively treat volume overload? |
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Definition
1) Diuretics to decrease reabsorption of sodium and increase secretion
2) Decrease oral Na intake
3) Treat co-morbid conditions (i.e. inotropes in CHF) |
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Term
What are the important characteristics of the following 3 rare disorders of sodium retention?
1) Syndrome of apparent mineralocorticoid excess
2) Liddle's Syndrome
3) Gordon's Syndrome |
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Definition
1) Inactivation of 11b-OHSD (mutations or licorice), which prevents inactivation of cortisol into cortisone.
- Inappropriate MR stimulation in aldosterone-sensitive tissues where cortisol is usually inactivated causes chronic Na reabsorption in the kidney.
2) Gain of function mutation in ENaC in distal tubule causes abnormal Na reabsorption
3) Overactivity of Na,Cl co-transporter in early distal tubule and inhibition of ROMK |
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Term
| What rare disorder(s) of the kidney could explain HTN, low renin levels, low aldosterone levels and hypokalemia? |
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Definition
BOTH
1) Syndrome of apparent minderalcorticoid excess (11b OHSD mutation or licorice)
2) Liddle's syndrome (ENaC GOF mutation) present this way |
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Term
What disease is associated with each of the following
1) ENaC gain of function mutation
2) NCC over activity
3) NCC inhibition
3) ROMK inhibition
4) ROMK stimulation
5) Na,K,2Cl- transporter mutation
6) Too much cortisol stimulation of MR
7) ENaC underactivity
8) MR inhibition |
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Definition
1) Liddle's syndrome- HTN, low renin, low aldosterone, Hypokalemia
2) Gordon's syndrome- HTN and Hyperkalemia
3) Gitelman's syndrome (thiazide-like)- Hypokalemia, elevated renin/aldosterone, normal ECF and BP
4) Bartter Syndrome (loop-diuretic like)- same presentation as Gitelman
5) Also Bartter Syndrome
6) Syndrome of apparent mineralcorticoid excess (11b-OHSD)
7-8) Pseudohypoaldosteronism Type 1 |
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Term
| How can you tell Gordon's syndrome from Liddle's syndrome clinically? |
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Definition
Potassium!
Liddle's will have HTN, but with LOW potassium because of ENaC hyperactivity in the distal tubule (more excreted)
Gordon's will have HTN, but with HIGH potassium because of ROMK inhibition |
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Term
| How does Liddle's syndrome relate to Pseudohypoaldosteronism Type 1? |
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Definition
1) Liddle's is volume overload due to GOF mutation in ENaC channel in late distal tubule
2) Pseudohypoaldosteronism is volume depletion due to LOF mutation in ENaC leading to aldosterone insensitivity. |
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Term
| How does Bartter syndrome relate to Gordon's syndrome? |
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Definition
Both involve LOF mutation in ROMK channel responsible for potassium recycling and paracellular cation transport in the loop of henle.
However, Bartter also involves LOF in Na,K,2Cl transporter in loop of henle (VOLUME DEPLETION), and Gordon's syndrome involves over-actvity of NCC in early distal convoluted tubule (VOLUME OVERLOAD).
Therefore, Gordon's presents with hyperkalemia and Bartter's presents with hypokalemia. |
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