Chapter Sixteen, part 2
Channel Your Enthusiasm
Heart Failure and Hepatorenal Syndrome Insights
This chapter explores the complex landscape of heart failure and liver complications such as cirrhosis and ascites. It intricately examines the physiological mechanisms linking these conditions, highlighting outdated treatment practices and new understandings of sodium retention and kidney function. The discussion further contrasts treatment approaches for Acute Tubular Necrosis and Hepatorenal Syndrome, emphasizing the need for a prognosis-based strategy in managing patients requiring dialysis.
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
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
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
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