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Flashcards in 7 Disorders of Volume Homeostasis Deck (25):
1

Total body water (TBW)

  • TBW in men vs. women
  • TBW distribution

  • Total body water (TBW) in men vs. women
    • Men: TBW = 60% of body weight
    • Women: TBW = 50% of body weight
  • TBW distribution
    • Intracellular (IC) comparment: 2/3 (28 L)
    • Extracellular (EC) compartment: 1/3 (14 L)
      • Interstitial (IT) compartment: 3/4 (10.5 L)
        • Outside blood vessels but not in cells
      • Intravascular (IV) compartment: 1/4 (3.5 L)
        • In blood vessels

2

Normal water homeostasis

  • Water movement b/n EC & IC
  • Cations in EC vs. IC
  • Disorders of volume

  • Water movement b/n EC & IC
    • Water moves freely i.r.t. changes in osmotic & hydrostatic pressure
  • Cations in EC vs. IC
    • IC principal cation: K
    • EC principal cation: Na
    • Na/K ATPase maintains these cations in the relative compartments
  • Disorders of volume
    • Volume depletion & volume overload
    • Refer to changes in EC volume
    • ► disorders of Na depletion or Na excess

3

Causes of disorders of volume depletion

  • Disorders of volume depletion
  • GI losses
  • Renal losses
  • Skin/respiratory losses
  • Other

  • Disorders of volume depletion
    • Loss of fluid (Na & water) from the EC (IV + IT)
  • GI losses
    • Vomiting
    • Diarrhea
    • Acute hemorrhage (i.e., GI bleeding or trauma)
    • nasogastric suction
  • Renal losses
    • Diuretics (--> Na & water excretion)
    • Osmotic diuresis (i.e., diabetes --> hyperglycemia --> polyuria)
    • Renal salt wasting disorders
  • Skin/respiratory losses
    • Fever
    • Excessive sweating
    • Burns
  • Other
    • Bleeding
    • Pancreatitis

4

Clinical signs & symptoms of volume depletion

  • IV signs/symptoms
  • IT signs/symptoms
  • Renal effects
  • Strong symptom of volume depletion

  • IV signs/symptoms
    • Hypotension --> dizziness
    • Orthostatic HoTN (drop in BP upon standing) --> dizziness
    • Tachycardia
    • Low JVP
  • IT signs/symptoms
    • Poor skin turgor / tenting
    • Dry mucous membranes
  • Renal effects
    • Decreased renal blood flow
    • Decreased glomerular filtration
  • Strong symptom of volume depletion
    • Thirst

5

Physiological responses to restore EC volume i.r.t. decreased EC volume

  • Response to low urine Na + concentrated urine
  • Response to diuretics & rare disorders of renal salt wasting (not low urine Na)
  • Effect of HoTn & hypovolemia
    • Renal hypoperfusion w/ decreased delivery of NaCl to the macula densa
    • SNS activation
    • Decreased IV volume

  • Response to low urine Na + concentrated urine
    • RAAS activation
    • --> Na retention
    • --> water retention
  • Response to diuretics & rare disorders of renal salt wasting (not low urine Na)
    • SNS activation --> maintain perfusion to vital organs
    • --> vasoconstriction
    • --> increased cardiac contractility
  • Effect of HoTn & hypovolemia
    • Renal hypoperfusion w/ decreased delivery of NaCl to the macula densa
      • --> renin --> AI --> AII --> aldo
      • --> Na reabsorption
      • --> expanded EC
    • SNS activation
      • --> AII
      • --> peripheral vasoconstriction
      • --> increase HR
      • --> restore BP
    • Decreased IV volume
      • --> volume baroreceptor stimulation
      • --> ADH (vasopressin) release
      • --> water retention

6

AII

  • General
  • Effects
  • Moderate volume depletion
  • Severe volume depletion

  • General
    • Principal hormonal regulator involved in the physiological response to hypovolemia
    • Generated i.r.t. low EC volume
  • Effects
    • Systemic arterial vasoconstriction
    • Release of aldo from teh adrenal gland
    • Initial maintenance of glomerular filtration by EffA > AffA constriction
  • Moderate volume depletion
    • GFR is maintained while RBF decreases
    • Prostaglandins vasodilate AffA
  • Severe volume depletion
    • GFR & RBF decrease
    • High levels of AII constrict both EffA & AffA
    • Decrease BP --> decrease overall renal perfusion

7

Aldosterone

  • General
  • Activates/stimulates...

  • General
    • Principal hormonal regulator involved in the physiological response to hypovolemia
    • Secreted i.r.t. increased AII
  • Activates/stimulates in the distal tubule & collecting duct
    • Na/Cl co-transporter
    • ENAC
    • Basolateral Na/K ATPase
    • Na reabsorption

8

ADH (vasopressin)

  • General
  • Released i.r.t. ...
  • Primary effect
  • Secondary effect
  • Osmotic vs. non-osmotic secretion

  • General
    • Principal hormonal regulator involved in the physiological response to hypovolemia
    • Released from the posterior pituitary
  • Released i.r.t. ...
    • Primary: increased plasma osmolarity
    • Secondary: decreased blood volume / pressure (baroreceptors in carotid sinus)
  • Primary effect
    • Increase water reabsorption in the collecting duct
  • Secondary effect
    • Increase Na retention by activating the Na/K/2Cl co-transporter int he TkAL & ENAC in the collecting duct
  • Osmotic vs. non-osmotic secretion
    • Volume depletion despite normal or low plasma osmolality --> non-osmotic secretion of vasopressin

9

Treatment of disorders of volume depletion

  • Re-expand the EC space
  • Reverse the primary etiology
  • Hormonal response

  • Re-expand the EC space by expanding the IV space
    • ​IV fluids (principally isotonic saline or other isotonic fluid)
  • Reverse the primary etiology
    • Anti-emetics for vomiting
    • Treatment for diarrhea
    • Withdrawal of diuretics
  • Hormonal response
    • Decrease activated RAAS --> decrease release of renin, AII, & aldo
    • Decrease baroreceptor stimulation --> reduce ADH secretion

10

Bartter syndrome

  • General
  • Loss of function
  • Resembles
  • Clinical presentation

  • General
    • Very rare inherited disorder of renal Na loss
  • Loss of function: TkAL
    • Na/K/2Cl transporter
    • ROMK channel
    • Basolateral Cl channel
  • Resembles
    • Loop diuretic
    • Increase Na urinary excretion
  • Clinical presentation
    • Low to normal EC volume
    • Low to normal BP
    • Elevated renin & aldo
    • Low K
    • Onset in early childhood

11

Gitelman's syndrome

  • General
  • Loss of function
  • Resembles
  • Clinical presentation

  • General
    • Very rare inherited disorder of renal Na loss
  • Loss of function: early distal tubule
    • Na/Cl co-transporter
  • Resembles
    • Thiazide diuretic
  • Clinical presentation
    • Low to normal EC volume
    • Low to normal BP
    • Elevated renin & aldo
    • Low K
    • Hypocalciuria

12

Pseudohypoaldosteronism type I

  • General
  • Loss of function
  • Resembles
  • Clinical presentation

  • General
    • Very rare inherited disorder of renal Na loss
    • AR disorder
  • Loss of function: late distal tubule
    • Either ENAC channel or mineralocorticoid receptor
    • Either makes collecting tubule unable to respond to aldo
  • Resembles
    • K sparing diuretic
  • Clinical presentation
    • Volume depletion
    • HoTN
    • Hyperkalemia despite elevated plasma aldo

13

Disorders of volume expansion/overload

  • General
  • Common causes
  • Less common causes

  • General
    • Expansion of the EC space
  • Common causes
    • Advanced renal failure
    • Heart failure
    • Liver failure
    • Nephrotic syndrome
  • Less common causes
    • Other clinical conditions
    • Certain medications

14

Clinical signs & symptoms of volume overload

  • Increased Na & water in the IT
  • Increased Na & water in the IV
  • 2 factors that drive the formation of edema

  • Increased Na & water in the IT: edema
    • Lung: pulmonary edema --> dyspnea
    • Extremities: peripheral edema --> swelling (most commonly lower)
    • Abdomen: ascities --> abdominal distention & weight gain
  • Increased Na & water in the IV: HTN
    • Sometimes see HoTN
  • 2 factors that drive the formation of edema
    • Renal retention of Na & water
    • Change in capillary starling forces
      • Net movement of fluid out of the capillary bed & into the interstitial space
      • Balance b/n hydrostatic pressure & oncotic pressure in capillaries & interstitium

15

Volume overload associated w/ advanced & end-stage renal failure

  • Relates principally to...
  • Decreased "effective" arterial volume
  • Clinical disorders w/ decreased effective arterial volume

  • Relates principally to...
    • Retention of Na & water + increased hydrostatic pressure
  • Decreased "effective" arterial volume
    • Disease states associated w/ both an expansion of the ECFV & underfilling of the arterial bed
  • Clinical disorders w/ decreased effective arterial volume
    • CHF
    • Cirrhosis
    • Certain cases of nephrotic syndrome

16

Volume overload associated w/ heart failure

  • Effective circulating volume in CHF
  • Clinical presentation

  • Effective circulating volume in CHF: low
    • Low cardiac output --> low pressure at baroreceptors --> low blood flow to kidneys
    • Kidneys sense low blood flow --> activate hormonal mechs of true EC volume depletion (renin, AII, aldo, ADH)
    • --> Na & water retention
  • Clinical presentation
    • LHF --> pulmonary edema + dyspnea
    • RHF --> peripheral edema + ascites
    • Biventricualr failure --> pulmonary edema + peripheral edema + ascites

17

Volume overload associated w/ liver failure

  • Decrease systemic vascular resistance / splanchnic vasodilation
    • --> decrease effective circulating volume
    • --> increase SNS & RAAS
    • --> Na retention
  • Increase hepatic sinusoidal pressure
    • --> increase Pcap in hepatic sinusoids
    • --> ascites
  • Hypoalbunemia
    • --> decrase πcap
    • --> edema

18

Volume overload associated w/ nephrotic syndrome

  • Defined by...
  • Results from...

  • Defined by...
    • Glomerular leak of protein + substantial loss of protein/albumin in urine
    • --> hypoalbuminemia (low albumin in blood)
  • Results from...
    • Hypoalbuminemia --> πcap --> edema
    • Primary na retention

19

Treatment of volume overload

  • General
  • Heart failure
  • Cirrhosis
  • Nephrotic syndrome

  • General
    • Diuretics
      • Decrease Na reabsorption in tubule
      • Increase Na excretion in urine
    • Decrease oral Na intake
  • Heart failure
    • Inotropes (sometimes)
  • Cirrhosis
    • Liver transplant
  • Nephrotic syndrome
    • Treat glomerular disease w/ steroids, cytotoxics, etc.
    • ACE-Is

20

Syndrome of apparent mineralocorticoid excess

  • General
  • Background
  • When syndrome occurs
  • Pathology
  • Clinical presentation

  • General
    • Very rare disorder of Na retention
  • Background
    • 11beta-hydroxysteroid dehydrogenase (11beta OHSD) converts cortisol to cortisone
    • Cortisone is inactive on mineralocorticoid receptors
  • When syndrome occurs: 11beta OHSD inactivation due to...
    • Certain types of licorice w/ glycyrrhizic acid
    • Mutations of 11beta OHSD
  • Pathology
    • Cortisol can activate either the glucocorticoid receptor (GR) or mineralocorticoid receptor (MR)
    • TO prevent chronic & inappropriate activation of MR, 11beta OHSD converts cortisol to cortisone in adlo sensitive tissues
    • 11beta OHSD is inactivated & chronic, inappropriate MR signaling happens if...
      • Pt has the syndrome of apparent mineralocorticoid excess (mutation that inactivates 11beta OHSD)
      • Pt ingests natural licorice (glycyrrhizic acid)
  • Clinical presentation
    • HTN
    • Hypokalemia
    • Low aldo levels

21

Liddle's syndrome

  • General
  • Caused by...
  • Clinical presentation

  • General
    • Very rare disorder of Na retention
  • Caused by...
    • Over activity of the ENAC in the distal tubule (gain of function mutation)
  • Clinical presentation
    • HTN
    • Low renin
    • Low aldo
    • Hypokalemia

22

Gordon's syndrome

  • General
  • Caused by...
  • Clinical presentation

  • General
    • Very rare disorder of Na retention
  • Caused by...
    • Over activity of the Na/Cl co-transporter in the distal tubule
    • Inhibition of ROMK
  • Clinical presentation
    • HTN
    • Hyperkalemia

23

Case: 61yo male w/ 5 days of nausea, vomiting, diarrhea, abdominal pain, & decreased appetite

  • Total EC volume
  • IV volume
  • Effective circulating volume
  • Sympathetic tone
  • Renin, AII, & aldo
  • ADH
  • Urine Na
  • Hormone primarily responsible for urine Na concentration

  • Total EC volume
    • Decreased
  • IV volume
    • Decreased
  • Effective circulating volume
    • Decreased
  • Sympathetic tone
    • Increased
  • Renin, AII, & aldo
    • Increased
  • ADH
    • Increased
  • Urine Na
    • Decreased
  • Hormone primarily responsible for urine Na concentration
    • Aldo (RAAS)

24

Case: 74yo female w/ heart failure, dyspnea, peripheral edema, & 18 lb weight gain

  • Total body Na
  • EC volume
  • IT volume
  • Effective circulating volume
  • RAAS
  • Urine Na
  • Urine (concentrated or dilute)
  • Hormone responsible for urine concentration

  • Total body Na
    • Increased
  • EC volume
    • Increased
  • IT volume
    • Increased
  • Effective circulating volume
    • Decreased
  • RAAS
    • Increased
  • Urine Na
    • Decreased
  • Urine (concentrated or dilute)
    • Concentrated
  • Hormone responsible for urine concentration
    • ADH (vasopressin)

25

Summary

  • Primary cation in EC
  • Components of EC space
  • Cause of volume depletion or overload
  • Volume depletion activation of SNS & RAAS
  • Decreased effective circulating volume
  • What causes edema

  • Primary cation in EC
    • Na
  • Components of EC space
    • IV & IT
  • Cause of volume depletion or overload
    • Too little or too much volume in the EC space
  • Volume depletion activation of SNS & RAAS
    • Renin --> AII --> aldo --> Na reabsorption
    • ADH --> water reabsorption
  • Decreased effective circulating volume
    • Certain cases of volume overload: CHF, cirrhosis
    • Increased total volume in EC but underfilling of arterial bed
    • --> Activation of RAAS --> volume expansion
  • What causes edema
    • Disruption of balance b/n hydrostatic & oncotic pressure in capillaries & interstitium