Edematous States & Diuretics

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Edematous states & Diuretics


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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


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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]


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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


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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.


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Congestive heart failure

Cardiac dysfunction

Cardiac output

Renal Na & waterRetention

Blood volume

venous pressure

EDEMA


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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.


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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


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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


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Pathogenic mechanisms responsible for the activation of vasoactive

systems and hyperdynamic circulation in cirrhosis


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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.


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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


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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


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especially with thiazides


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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


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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


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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

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Edematous States & Diuretics