References

We talked about winning the 2022 ASN innovation contest and here’s a link to our promo video https://www.dropbox.com/scl/fi/g4osnf0nradsfryyo51fi/ASN-Education-Contest-Channel-Your-Enthusiasm-Podcast.mp4?rlkey=pnso45x07nr3pane9y8cux8yg&e=1&dl=0

We wondered about “permissive hypercreatinemia” and Josh referenced the DOSE trial: Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial - PMC

Plus this editorial by Steve Coca: Ptolemy and Copernicus Revisited: The Complex Interplay between the Kidneys and Heart Failure

We refer to the Frank-Starling curve and reference an image from this paper by Jay Cohen: Blood pressure and cardiac performance - ScienceDirect

We felt that this chapter is dated with respect to heart failure. Check out this 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Underfilling versus overflow in hepatic ascites an editorial by Frank Epstein

Effect of Head-Out Water Immersion on Hepatorenal Syndrome - American Journal of Kidney Diseases studies done by Schrier which Roger mentioned

The fading concept: https://www.tandfonline.com/doi/abs/10.3109/00365528309182102?journalCode=igas2

Historical Aspects of Ascites and the Hepatorenal Syndrome - Wong - 2021 - Clinical Liver Disease - Wiley Online Library

Here’s a great paper from Andrew Allegretti on HRS prognosis: Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT - PubMed

Joel mentions landmark paper in NEJM for treating SBP Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis | New England Journal of Medicine

Albumin infusion in patients undergoing large‐volume paracentesis: A meta‐analysis of randomized trials - Bernardi - 2012 - Hepatology - Wiley Online Library

Joel wondered about the lore that minoxidil could lead to renal recovery: Minoxidil treatment of malignant hypertension. Recovery of renal function

Roger recalled an agent diazoxide: Hyperstat - Side Effects, Uses, Dosage, Overdose, Pregnancy, Alcohol | RxWiki

Here’s an entertaining review on whether insulin leads to sodium retention: Invited Review: Sodium-retaining effect of insulin in diabetes - PMC

Invasive monitoring for hemodynamics

FACTT: https://www.nejm.org/doi/full/10.1056/NEJMoa062200

ESCAPE: https://pubmed.ncbi.nlm.nih.gov/16204662/

PACMAN: https://pubmed.ncbi.nlm.nih.gov/16084255/

EVEREST trial and use of tolvaptan in HFrEF

EVEREST: https://pubmed.ncbi.nlm.nih.gov/17384437/

Post-hoc analysis of hyponatremic patients of EVEREST: https://pubmed.ncbi.nlm.nih.gov/23743487/

Outline Chapter 16 — Edematous States part 2

Symptoms and diagnosis

Three factors important in the mechanism of edema

The pattern of distribution of edema which reflects those capillaries with altered hemodynamic forces

The central venous pressure

Presence or absence of pulmonary edema

Pulmonary edema

Shortness of breath and orthopnea

Tachypnic, diaphoretic, wet rales, gallops, murmurs

Check a chest x-ray

Cardiac disease is most common

But differential includes primary renal Na retention and ARDS

Wedge pressure will exceed 18-20 mmHg with heart or primary Na retention, but is relatively normal with ARDS

Uncomplicated cirrhosis does not cause pulmonary edema

Increased capillary pressure in this disorder is only seen below the hepatic vein

Normal or reduced blood volume in the cardiopulmonary circulation

Peripheral edema and ascites

Peripheral edema is cosmetically undesireable but produces less serious symptoms

Symptoms: swollen legs, difficulty walking, increased abdominal girth, shortness of breath due to pressure on the diaphragm.

Pitting edema found in dependent areas

Ascites found in abdomen

Nephrotic syndrome low tissue pressure areas like eye orbits

Heart Failure (right sided) peripheral edema, abdominal wall, SOB is due to concomitant pulmonary disease. Right sided heart failure increases venous pressure

Cirrhosis develop cirrhosis and lower extremity edema, pressure above the hepatic vein is normal or low.

Tense ascites can increase the pressure above the diaphragm but is relieved with a tap

Portal pressure > 12 mmHg required for fluid retention

Love the case history 16-1

Primary renal sodium retention

Pulmonary and peripheral edema

Jugular venous pressure is elevated

Nephrotic Syndrome

Periorbital and peripheral edema, rarely ascites

CVP normal to high

Idiopathic edema

Behaves as volume depleted (especially with diuretics)

Etiology and treatment

General principles of treatment

When must edema be treated

What are the consequences of the removal of fluid

How rapidly should fluid be removed

When

Pulmonary edema is the only form of generalized edema that is life threatening and demands immediate treatment

Important for note: laryngeal edema and angioedema. Cerebral edema

What are the consequences

If the edema fluid is compensatory (heart failure, cirrhosis, capillary leak syndromes) then removal of fluid with diuretics will diminish effective circulating volume.

Despite this drop in effective circulating volume, most patients benefit from the appropriate use of diuretics.

Cardiac output falls 20% with diuresis of pulmonary congestion but exercise tolerance increases

Says to be careful in diuresis leads to increases in Cr

How rapidly should edema fluid be removed

Removing vascular fluid changes starling forces (reduced venous pressure) so fluid rapidly mobilized from interstitium. 2-3 liters per 24 hours can often be removed without difficulty

An exception is cirrhosis and ascites without peripheral edema. Mobilizing ascites is limited to 500-750 ml/day

Heart failure

Edema is due to increase in venous pressure raising capillary hydrostatic pressure

Ischemic and hypertensive CM impairs left ventricular function causing pulmonary but little peripheral edema

In acute pulmonary edema the LV disease results in increased LVEDP and increased left atrial pressure which transmit back to the pulmonary vein

When wedge exceeds 18-20 (normal is 5-12) get pulmonary edema

Cor pulmonale due to pure right heart failure prominent edema in the lower extremities

Cardiomyopathies tend to affect right and left ventricles leading to simultaneous onset of pulmonary and peripheral edema.

Discusses forward hypothesis in which reduction in cardiac output triggers decreased tissue perfusion activation of SNS and RAAS.

Catecholamines increase cardiac output

RAAS increase Sodium retention

Edema is absent and patients can be compensated at the expense of increased LVEDP see Figure 16-6

Figure 16-6 A to B to C with compensation

Eventually the increased sodium retention and increased intracranial pressure are enough to cause edema.

He then brings up multiple important points (in bullets none the less)

Dual effects of fluid retention:

Increased cardiac output

Potential harmful elevation in venous pressure

Benefit is found with increase in LVEDP from 12 to 15, after that it seems mostly deleterious

Vascular congestion (elevated LVEDP) and a low cardiac output do not have to occur together. See points B and C on 16-6.

Frank-Starling relationship varies with exercise.

Patients with moderate heart disease may be okay at rest but fail with mild exertion. This leads to more neurohormonal activation. This can worsen sodium retention and ischemia. Rest here can help augment diuretic effect. Doubling diuretic response. 40% increase in GFR.

Mild to mod heart disease may have no edema with dietary Na restriction. Na intake will initially increase preload and improve cardiac output and allow the Na to be excreted but as the Frank Starling curves flatten then excess sodium cannot be excreted.

Diastolic vs Systolic dysfunction

Decreased compliance in diastolic dysfunction can lead to flash pulmonary edema

More common with hypertension

Look to the ejection fraction

Neurohormonal adaptation

Initial benefit long term adverse effects

Norepi, renin, ADH all are vasoconstrictors

They raise cardiac output

Raise BP which is maladaptive in the long term

Treatment of cardiogenic pulmonary edema

Morphine

Oxygen

Loop diuretic

NTG/nitroprusside

If patient remains in pulmonary edema and has systolic dysfunction consider inotropic agent

Treatment of chronic heart failure

Feels dated

Mentions dig and loop diuretic

But also ACEi/BB and AA

Deep dive

Loop diuretics

ACEi

Cor Polminale

Edema here comes with increased CO2

Associated with increased HCO3 which means increased

HCO3 reabsorption int he proximal tubule which leads to more sodium retention

Hypoxemia can increase Na retention

Cirrhosis and Ascites

Both lymphatic obstruction and increased capillary permeability contribute

Sinusoidal obstruction leads to increased hydraulic pressure in the sinusoids.

Portal hypertension is necessary for ascites

> 12 mmHg

The low albumin is often present but is not contributory to edema

Sinusoids are freely permeable to albumin so no oncotic pressure from albumin here

Mechanism of ascites

Renal sodium conservation is an early finding and some evidence for primary sodium retention but…

Mostly underfill is thought to drive Na retention

Splanchnic vasodilation starts this of

NO drives this

Endotoxin absorption stimulates No

Normally endotoxin is detoxed in liver but portosystemic shunting allows endotoxin to escape the liver.

Hepatorenal syndrome

Progressive hemodynamically mediated fall in GFR

Induced by intense renal vasocontstriction

Where are the PGE and Kinins

Fall in GFR is masked by decreased muscle mass and decreased BUN production

Hyponatremia is a grave prognostic sign, as it is in heart failure, Indicates increased activation of vasopressin

Treatment

Low Na intake

Low water intake

Care with diuretics, can only mobilize 300-500 ml of ascetic fluid a day

Avoid hypokalemia

Stimulates NH3 production

Talks about the mechanism in proximal tubule

Also discusses pKA of NH3->NH4 reaction and if the pH rises, this will shift the Eq to produce NH3

Important aspect in NH3 is lipid soluble and NH is not

Says that Spiro is diuretic of choice

States it is more effective than furosemide in this condition

Effectiveness related to slower rate of drug excretionin urine (compromises furosemide but not spiro) competition with bile salts

Recommends 40 furosemide and 100 of spiro

Resistant ascites

Options

paracentesis

TIPS

Complicated by higher mortality

Peritoneovenous shunt

Largely abandoned,

Primary renal sodium retention

CKD or AKI where low GFR linits excretion of Water and Na

Acute GN or nephrotic syndrome

Broken glom with intact tubules, mean the tubules see less Na so they think “underperfused” and then they increase renal retention of NA

Drugs

Direct vasodilators like minoxidil

Require super high furosemide doses to counter

Other antihypertensives either block sympathetic NS, Na retention directly or block RAAS explains why they don’t cause Na retention

NSAIDS

Fludrocortisone

Pregnancy

Normal pregnancy is associated with retention of 900 to 1000 mEq of Na

And! 6-8 liters of water

Refeeding edema

Insulin stimulate Na retention

UFOs, Balloons, Asteroids, Oh My! 🛸