edematous states & diuretics
TRANSCRIPT
-
7/27/2019 Edematous States & Diuretics
1/24
Edematous states & Diuretics
-
7/27/2019 Edematous States & Diuretics
2/24
-
7/27/2019 Edematous States & Diuretics
3/24
2 basic steps in edema formation Alteration in capillary haemodynamics that favors the movement of fluid from the vascular
space to the interstitium
Dietary Na & water are retained by the kidney
Major causes of edematous states Increased capillary hydrolic pressure
Increased plasma volume due to renal Na retention: heart failure
Primary Na retention Renal ds incl. NS
Drugs: minoxidil, CCB, diazoxide, NSAIDS, fludrocortisone, estrogen
Refeeeding edema
Early hepatic cirrhosis
Pregnancy Idiopathic edema, when diuretic induced
Venous obstruction Hepatic venous obstruction, hepatic cirrhosis,
Acute pulmonary edema, Local venous obstruction
Decreased arteriolar resistance CCB, idiopathic edema
Decreased oncotic pressure (alb
-
7/27/2019 Edematous States & Diuretics
4/24
Renal sodium retention
Inability to excrete the Na & water that has
been ingested patients with renal disease.Appropriate compensatory response to
effective circulating volume depletion, withurine [Na]
-
7/27/2019 Edematous States & Diuretics
5/24
Intrarenal factors
Reflex activation of the sympathetic
nervous system
Activation of RAAS and ADH
Resistance to the action of natriuretic
peptides
Altered glomerular haemodynamics Peritubular forces in PT
-
7/27/2019 Edematous States & Diuretics
6/24
-
7/27/2019 Edematous States & Diuretics
7/24
General principles of treatment When must edema be treated?
Pulmonary edema is life threatening and demands immediate treatment
Other edematous states, removal of fluid can proceed more slowly
What are the consequencesof the removal of edema fluid? Is the retention of Na & water a compensatory response or inappropriate primary
Na retention?
If retention of edema fluid is compensatory then removal of this fluid withdiuretics should diminish the effective circulating volume.- decrease in venousreturn to the heart, and cardiac filling pressures fall in cardiac output
Leads to increased secretion of the hypovolemic hormones: renin,norepinephrine, ADH.
Most patients will benefit from the appropriate use of diuretics
Adequacy of tissue perfusion can be estimated by monitoring BUN & plasma [Cr]as long as these parameters remain constant, it can be assumed that diuretictherapy has not led to a significant impairment in perfusion to the kidney or,
therefore, to other organs. How rapidly should edema fluid be removed?
Fluid that is lost initially comes from the plasma; restoration of plasma volume isby mobilization of edema luid into the vascular space
In patients with generalized edema due t heart failure, nephrotic syndrome, orprimary Na retention, the edema fluid can be mobilized rapidly, since mostcapillary beds are involved
Important exception is hepatic cirrhosis with ascites but no peripheral edema
only 500-750 ml/d can only be removed safely.
-
7/27/2019 Edematous States & Diuretics
8/24
-
7/27/2019 Edematous States & Diuretics
9/24
Congestive heart failure
Cardiac dysfunction
Cardiac output
Renal Na & waterRetention
Blood volume
venous pressure
EDEMA
-
7/27/2019 Edematous States & Diuretics
10/24
Depressed ventricular contractility, induced by the underlying cardiac disease, leads to neurohumoral activation (moving
clockwise) that is initially adaptive in that it maintains blood pressure and tissue perfusion. Over the long-term, however,
the increase in outflow resistance (afterload) hastens the rate of myocardial deterioration and worsens ventricular
performance. This leads to a vicious cycle of increasing release of norepinephrine, angiotensin II, and ADH that further
increases afterload.
-
7/27/2019 Edematous States & Diuretics
11/24
HEPATIC CIRRHOSIS & ASCITES
HEPATIC DISEASE
UNDERFILLING OVERFLOW
Renal Na &
Water retention
Plasma volume
ASCITES
Hypo- Peripheral sinusoidalalbuminemia vasodilatation pressure
Splanchnic
pooling
ASCITES
Effective Circ
Volume
FURTHER ASCITES
Renal Na &
Water retention
-
7/27/2019 Edematous States & Diuretics
12/24
Circulatory, vascular, functional, and biochemical abnormalities in patients with
cirrhosis and ascites
Circulatory
Reduced systemic
vascular resistance
Reduced arterial pressure
Increased heart rate
Increased cardiac indexIncreased plasma volume
Reduced renal blood flow
Increased portal blood
flow
Vascular
Splanchnic
vasodilation
Renal artery
vasoconstriction
Pulmonary
vasodilation
Functional
Activation of systemic
vasodilator factors
Activation of systemic
vasoconstrictor factors
Activation of renal
vasodilator factors
Reduced glomerular
filtration rate
Biochemical
Sodium retention
Water retention
Increased systemic nitric
oxide
Increased systemicprostaglandins
Increased renal nitric oxide
and prostaglandins
-
7/27/2019 Edematous States & Diuretics
13/24
Pathogenic mechanisms responsible for the activation of vasoactive
systems and hyperdynamic circulation in cirrhosis
-
7/27/2019 Edematous States & Diuretics
14/24
-
7/27/2019 Edematous States & Diuretics
15/24
-
7/27/2019 Edematous States & Diuretics
16/24
Primary renal Na retention
RENAL Na RETENTION
Plasma volume
Capillary hydraulic pressure
EDEMA
Pathogenesis of edema in primary renal Naretention, which is most often due to
glomerular disease, advanced renal failure,
Or the use of potent vasodilators in the
treatment of hypertension.
-
7/27/2019 Edematous States & Diuretics
17/24
Drugs; direct vasodilators, minoxidil, diazoxide
CCB, dehydropyridines
Pregnancy; normal pregnancy is associated with retention of 1000meq Na
and 6-8L water
Refeeding edema
Insulin directly stimulates Na reabsorption in PT & perhaps in theloop of Henle & DT
Nephrotic syndrome
Idiopathic edema; in young menstruating women
May represent a capillary leak syndrome Dopamine deficiency & impaired hypothalamic function
Diuretic induced edema Chronic use of diuretics activates Na retaining mechanisms
-
7/27/2019 Edematous States & Diuretics
18/24
DIURETICS
Site of action Carrier/channel inhibited % filtered Namechanism excreted
Proximal Tubule inhibits Enz. Carbonic Anhydrase modest
Acetazolamide prevent NaHCO3 reabsorption
Loop of Henle Na K - 2Cl carrier up to 25%
Furosemide
Bumetamide
Ethacrinic acid
Distal tubule & Na Cl Carrier up to 3 5%
Connecting segment
Thiazides
ChlortalidonMetalazone
Cortical collecting tubule Na Channel up to 1 2%
Spironolactone blocks aldosterone receptor in cytoplasm
Amiloride
Triamterene
-
7/27/2019 Edematous States & Diuretics
19/24
-
7/27/2019 Edematous States & Diuretics
20/24
especially with thiazides
-
7/27/2019 Edematous States & Diuretics
21/24
Other effects Loop diuretics
Ca reabsorption in the loop of henle is primarily passive, driven by gradient created by NaCltransport
Increase Ca excretion
Treatment of hypercalcemia; NaCl solution & loop diuretic
Thiazide type diuretic DT is major site of active Ca reabsorption, independent of Na transport
Increase reabsorption of Ca, similar response occurs in the cortical collecting tubule withamiloride
Useful in treatment of kidney stones due to hypercalciuria
K-sparing diuretics Aldosterone sensitive Na channel
Can lead to hyperkalemia and metabolic acidosis
Trimetoprim at very high doses
Amiloride in the treatment of lithium induced nephrogenic DI
Triamterene is a potential nephotoxin; crystalluria, cast formation, triamterene stones
Acetazolamide Net diuresis is modest; reclaimed in the more distal segments, diuretic action limited by the
metabolic acidosis
Major indication: as a diuretic in edematous patients with metabolic alkalosis
Mannitol Osmotic diuretic, inhibiting Na & water reabsorption in PT, loop of Henle
Produces a relative water diuresis, water is lost > Na & K
Can cause increase in plasma osmolality;- can lead to water deficit and hypernatremia,
hypertonic mannitol may be retained in patients with renal failure
-
7/27/2019 Edematous States & Diuretics
22/24
Determinants of diuretic response
Site of action of the diuretic
Presence of counterbalancing antinatriureticforces, AII, hypotension.
Rate of drug excretion Most diuretics, particularly the loop diuretics, are
highly protein bound
Are poorly filtered, and enter the urine primarily viathe organic anion/cation secretory pump in PT
Their ability to inhibit Na reabsorption is in part dose -dependent
The natriuretic response tends to plateau athigher rates of diuretic secretion
-
7/27/2019 Edematous States & Diuretics
23/24
-
7/27/2019 Edematous States & Diuretics
24/24
General guidelines
Use the minimum effective dose
Use for as short a period of time as
necessary
Monitor regularly for adverse effects
Use only for appropriate conditions