Lecture 7: Disorders of Volume Homeostasis

Question 1

What are examples of disorders of volume depletion? (loss of Na and water from EC space

Answer 1

GI losses (vomitting diarrhea, acute hemorrhage, nasogastric suction)
renal losses (diuretics, osmotic diuresis, renal salt wasting disorders)
skin/respiratory losses (fever, excessive sweating, burns)
other - bleeding, pancreatitis

Question 2

What are signs and symptoms of lower IV volume?

Answer 2

hypotension --> dissiness
orthostatic hypotension
tachycardia
low JVP
renal effects: decreased renal blood flow, decreased GFR

Question 3

What are signs and symptoms of lower IT volume?

Answer 3

poor skin turgor/tenting

dry mucous membranes

Question 4

what are physiological responses to decreased EC volume?

Answer 4

activation of RAAS and SNS

Question 5

what are some very rare inherited disorders of renal Na loss?

Answer 5

bartter syndrome
gitelman syndrome
pseudohypoaldosteronism Type I

Question 6

Describe Bartter Syndrome

Answer 6

loss of function of Na,K,2Cl transporter, ROMK channel or basolateral Cl channel
resembles treatment with a loop diuretic
clinically presents with: 
low-normal EC volume
low-normal BP
elevated renin and aldosterone
low K+
onset early in childhood

Question 7

Describe volume overload with liver failure

Answer 7

there is decreased systemic vascular resistance and splanchnic vasodilation –> decreased effective circulating volume –> increased SNS + RAAS –> Na retention by kidney
increased hepativ sinusoidal pressure –> increased Pcap in hepatic sinusoids –> ascites
hypoalbuminemia –> decreased oncotic capillary pressure –> edema

Question 8

Describe volume overload in nephrotic syndrome

Answer 8

in nephrotic syndrome: glomerular leak of protein and substantial loss of protein/albumin in urine –> hypoalbuminemia
volume overload results from:
hypoalbuminemia –> decreased oncotic capillary pressure –> edema
primary Na retention in kidney

Question 9

describe treatments of volume overload

Answer 9

diuretics
dietary restriction of Na
organ specific (heart - inotropes, cirrhosis - liver transplant, nephrotic syndrome: steroids, cytotoxics, ACE inhibitors)

Question 10

what are some rare disorders of Na retention?

Answer 10

syndrome of apparent mineralocorticoid excess
liddle’s syndrome
gordone’s syndrome

Question 11

Describe syndrome of apparent mineralocorticoid excess

Answer 11

the 11beta hydroxysteroid dehydrogenase converts cortisol to cortisone to prevent chronic and inappropriate activation of MR
this enzyme is inactive in this syndrome (mutations or licorice with glycyrrhizic acid) –> inappropriate signaling of MR –> chronic Na reabsorption
clinically: hypertension, hypokalemia, low aldosterone

Question 12

Describe liddle’s syndrome

Answer 12

caused by over activity of ENaC in distal tubule
gain of function mutation
presentation:
hypertension
low renin
low aldosterone
hypokalemia

Question 13

Describe Gordon’s syndrome

Answer 13

overactivity of Na,Cl co-transporter in distal tubule and inhibition of ROMK
Presentation:
severe hypertension and hyperkalemia