1. List the differential diagnosis of CHF. Right heart failure

Left heart failure

Pulmonary Hypertension

Output Failure

Disease and Characteristics: 1) Ischemic heart disease (myocardial infarction, severe CAD, papillary muscle dysfunction or rupture) -History of myocardial infarction, presence of infarction pattern on ECG, risk factors for coronary disease2) Idiopathic dilated cardiomyopathy - Heart failure in a patient with no coronary disease risk factors or known coronary disease 3) Hypertension - History of poorly controlled hypertension, presence of an S4 on physical examination, left ventricular hypertrophy on echocardiogram or ECG 4) Valvular heart disease (mitral regurgitation, aortic insufficiency, aortic stenosis, tricuspid regurgitation, pulmonic insufficiency) - Mitral regurgitation: ejection murmur at apex. Dyspnea on exertion, atrial fibrillation. Aortic stenosis: dyspnea with exertion, ejection murmur at base that radiates to carotid arteries, decreased carotid upstrokes, syncope, angina 5) Bacterial myocarditis (Borrelia burgdorferi [Lyme disease], diphtheria, rickettsia, streptococci, staphylococci) - Fever, exposure to known agent, positive blood cultures 6) Parasitic myocarditis (Trypanosoma cruzi [Chagas disease], leishmaniasis, toxoplasmosis) - Travel history to endemic areas, fever, peripheral stigmata of infection (This is rare in the U.S.)7) Familial dilated cardiomyopathies - Family history of heart failure or sudden cardiac death in blood relatives 8) Toxic cardiomyopathies (alcohol, anthracycline, radiation, cocaine, catecholamines) - History of exposure to the toxic agent 9) Collagen vascular disease (SLE, polyarteritis nodosa, scleroderma, dermatomyositis) - History of a collagen vascular disease, positive serology results for a collagen vascular disease, other stigmata of a collagen vascular disease 10) Granulomatous disease (Wegener's granulomatosis, giant cell arteritis), sarcoidosis - Arrhythmias (both atrial and ventricular) that are difficult to control, rapidly progressive left ventricular dysfunction 11) Endocrinologic/metabolic disorders (hyperthyroidism, acromegaly, hypothyroidism, uremia, pheochromocytoma, diabetes mellitus, thiamine deficiency, selenium deficiency, carnitine deficiency, kwashiorkor, carcinoid, obesity) - Clinical history, serum test for endocrine abnormality, long-term resident of a third world country or an endemic area for a nutritional deficiency (Nutritional deficiencies are very rare in the U.S.)12) Giant cell myocarditis - Intractable ventricular or supraventricular arrhythmias with rapidly progressive left ventricular dysfunction, Endomyocardial biopsy specimen may be used to confirm the diagnosis. Effective immunotherapy may be available but prognosis is poor. Patients should be transferred to a center capable of ventricular assist device placement and cardiac transplantation 13) Peripartum cardiomyopathy - Heart failure symptoms with left ventricular dysfunction within 6 months of a pregnancy 14) Neuromuscular disorders (Becker's muscular dystrophy, myotonic dystrophy, Friedreich's ataxia, limb-girdle muscular dystrophy, Duchenne muscular dystrophy) - Appropriate clinical history and physical examination as per the underlying disease 15) Cardiac transplant rejection - History of cardiac transplant, noncompliance with medications, shortness of breath, atrial or ventricular arrhythmias, tachycardia 16) Hypertrophic cardiomyopathies (hypertrophic cardiomyopathy [genetic], hypertension) - History of hypertrophic cardiomyopathy, family history of hypertrophic cardiomyopathy, echocardiographic and

ECG findings of hypertrophy, Screen for outflow tract gradient by physical examination, echocardiography, or cardiac catheterization 17) Restrictive cardiomyopathies (amyloidosis, sarcoidosis, hemochromatosis, Fabry's disease, glycogen storage diseases, Gaucher's disease, mucopolysaccharidosis, endomyocardial fibrosis, hypereosinophilic syndrome) - Appropriate history, thickening of the myocardium on echocardiogram suggesting an infiltrative process, cardiac MRI showing infiltration, family history of an inborn error of metabolism or amyloidosis, presence of S4 on examination, right-sided heart failure more severe than left-sided, other organs involved in underlying disease process Pulmonary and other conditions that can mimic or exacerbate heart failure: 18) Asthma - Dyspnea at rest and with exertion, Physical examination reveals wheezing, Symptoms may be relieved by β-agonist inhalers 19) Pulmonary embolism - Pleuritic chest pain, tachycardia, evidence of DVT. Right heart strain pattern on ECG and seen on echocardiogram 20) Atrial fibrillation - Palpitations, syncope, rapid irregular pulse, May be a consequence or cause of heart failure 21) Supraventricular arrhythmias - Rapid heart rhythm, syncope, palpitations 22) Chronic obstructive pulmonary disease - Dyspnea at rest or with exertion, chest x-ray findings consistent with COPD 23) Septic shock - Hypotension, fever 24) Pneumonia - Fever, cough, sputum production, focal pulmonary consolidation on physical examination, characteristic chest x-ray findings 25) Interstitial pulmonary disease - Dyspnea, arterial oxygen desaturation with exercise, characteristic pulmonary function testing abnormalities, characteristic high-resolution chest CT scan findings 26) Sleep apnea - Fatigue, frequent napping, difficulty concentrating, obesity, bed partner notes irregular breathing or apneas during sleep, snoring, atrial fibrillation, hypertension, Obstructive sleep apnea is associated with obesity. Severe heart failure associated with central sleep apnea 27) Renal insufficiency - Uremic symptoms, edema, dyspnea, fatigue, May be a consequence or a cause of heart failure 28) Anemia - Fatigue, dyspnea on exertion, pallor, Associated with “high-output” heart failure

2 Describe the etiology of cardiomyopathy.Dilated- Left and/or right ventricular dilatation with impaired contractile function (primarily systolic) is characteristic of this disorder.Toxins-

Ethanol Chemotherapeutic agents: doxorubicin, bleomycin Cobalt Antiretroviral agents: zidovudine, didanosine, zalcitabine Phenothiazine Carbon monoxide Lead Mercury Cocaine

Metabolic-

Nutritional deficiencies:   Thiamine, selenium, carnitine Endocrinologic disorders:  Diabetes mellitus, hypothyroidism, thyrotoxicosis, Cushing's disease,

acromegaly, pheochromocytoma Electrolyte disturbances:  Hypocalcemia, hypophosphatemia

Familial-

Infectious-

Viral:   Coxsacki virus, cytomegalovirus, human immunodeficiency virus Rickettsial Bacterial: diphtheria Mycobacterial Fungal Parasitic:   Toxoplasmosis, Trichinosis, Chagas' disease Collagen vascular disorders-  Systemic lupus erythematosus, progressive systemic sclerosis,

dermatomyositis Hypersensitivity myocarditis-  sarcoidosis, peripartum dysfunction

Neuromuscular dysfunction-

Duchenne's muscular dystrophy Fascioscapulohumeral muscular dystrophy Erb's limb girdle dystrophy Myotonic dystrophy Fredreich's ataxia

Hypertrophic cardiomyopathy is a genetic disorder. Most patients have a positive family history consistent with an autosomal dominant pattern of inheritance. Missense mutations of genes that encode the cardiac sarcomeric proteins (beta-myosin heavy chain, cardiac troponin T, myosin-binding protein C, alpha-tropomyosin, and beta-myosin light chains) are present.

The pathophysiology of HOCM is complex and involves various mechanisms. The pattern of hypertrophy is asymmetric, affecting the interventricular septum more than the posterolateral segments of the left ventricle. An apical or concentric distribution may be present. Initial contraction of the ventricle is usually normal however as outflow from the left ventricle progresses and the ventricle contracts outflow obstruction can occur. Outflow tract obstruction is dynamic and changes with preload, afterload and contractility. Conditions that decrease the preload (hypovolemia, diuretics, Valsalva), decrease the afterload (vasodilators), and increase the contractility (exercise, sympathomimetics) can increase the pressure gradient and the outflow obstruction. Systolic anterior motion of the mitral valve (SAM) is the apposition of the anterior mitral valve leaflet against the hypertrophied septum during systole. The obstruction increases diastolic filling pressures leading to decrease in cardiac output and myocardial ischemia. Secondary mitral regurgitation can occur in patients with SAM.

Restrictive-Impaired ventricular filling due to high ventricular pressures results in diastolic dysfunction. Systolic function is often preserved.Myocardial

Noninfiltrative Idiopathic Familial Diabetic Infiltrative Amyloidosis

Sarcoidosis Fatty infiltration Gaucher's disease Storage diseases Hemochromatosis Fabry's disease Glycogen storage disease

Endomyocardial

Endomyocardial fibrosis Hypereosinophilic syndrome Carcinoid heart disease Metastatic cancers Radiation Anthracycline toxicity Drug-related fibrous endocarditis Serotonin Methysergide Ergotamine Mercurial agents Busulfan

3 Classify a patient with CHF based on New York Heart Association or AHA.It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regards to normal breathing and varying degrees in shortness of breath and or angina pain:

NYHA Class

Symptoms

INo symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.Life style change, stop smoking

IIMild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Ace inhibitor, beta blocker, diuretic, salt restriction,

IIIMarked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest.

IV Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

Look up stages in Kochar: A, B, and

C: same as A and B:

D: heart transplant, HOSPICE,

4. Describe adaptive mechanisms that occur with decreased left ventricular output.

The fall in cardiac output leads to increased sympathetic activity, which helps to restore cardiac output by increasing both contractility and heart rate. The fall in cardiac output also promotes renal salt and water retention leading to expansion of the blood volume, thereby raising end–diastolic pressure and volume which, via the Frank-Starling relationship, enhances ventricular performance and tends to restore the stroke volume. Left ventricular hypertrophy is also part of the adaptive response to systolic dysfunction, since it unloads individual muscle fibers and thereby decreases wall stress and afterload.

5. Compare and contrast systolic and diastolic dysfunction.

Diastolic Dysfunction - Diastolic heart failure (HF) is when patients have symptoms and signs of HF, normal or near normal left ventricular (LV) ejection fraction (EF), and evidence of diastolic dysfunction (abnormal left ventricular filling and elevated filling pressures). It is abnormal cardiac filling.

Diastolic dysfunction and diastolic heart failure are not synonymous terms. Diastolic dysfunction indicates a functional abnormality of diastolic relaxation, filling, or distensibility of the left ventricle (LV), regardless of whether the LVEF is normal or abnormal and whether the patient is asymptomatic or has symptoms and signs of HF. Thus, diastolic dysfunction refers to abnormal mechanical properties of the ventricle. DHF denotes the signs and symptoms of clinical HF in a patient with a normal LVEF and LV diastolic dysfunction.

It is most commonly caused by left ventricular hypertrophy. As the wall becomes thicker and stiffer the ventricle is harder to fill and the atria must work harder to fill it.

Predominantly diastolic dysfunction:

Marked left ventricular hypertrophy Hypertrophic cardiomyopathy Severe myocardial ischemia Mitral stenosis Left atrial mysoma Infiltrative cardiomyopathies (amyloidosis, hemochromatosis)

Abnormalities seen:

Poor filling due to decreased relaxation of the walls Normal ejection fraction Concentric hypertrophic remodeling Normal end-diastolic volume Increased wall thickness Increased ratio myocardial mass to cavity volume Increased ratio wall thickness to chamber radius Cardiomyocyte increased diameter

Systolic Dysfunction - Systolic dysfunction is characterized by abnormal pumping of the heart, that is, problems with contraction. The biggest difference from diastolic dysfunction (abnormal filling w/ normal ejection fraction) is a decreased ejection fraction.

The most common cause is ischemic heart disease due to coronary artery disease. It can also be caused by a Pressure overload (aka increased afterload caused by hypertension or obstruction to ventricular outflow) or Volume overload (aortic regurgitation, patent ductus or a VSD).

Predominantly systolic dysfunction:

Pressure Overload Hypertension Aortic Stenosis Coarctation of the aorta Pulmonary hypertension Pulmonary thromboembolic disease

Volume Overload Aortic incompetence Mitral incompetence VSD Atrial septal defect

Myocardial Contractile Failure Myocardial Infarction Dilate Cardiomyopathy

Abnormalities Seen:

Poor pumping (decreased contractility)o Decreased ejection fractiono Eccentric remodelingo Increased end-diastolic volumeo Increase left ventricular mass w/ little increase in wall thicknesso Decreased ratio of mass to volumeo Decreased ratio thickness to radiuso Cardiomyocyte elongation

6. Compare and contrast left and right heart failure including clinical presentation

ORTHOPNEA, shortness of breath: LEFT HEART FAILUREPND: LEFT HEART FAILURESWELLING OF LEGS: RIGHT HEART FAILUREJV DISTENTION: RIGHT HEART FAILUREHGR- HEPATOJUGULAR REFLEXCRACKLES: LEFT HEART FAILUREWHEEZES: LEFT HEART FAILUREPITTING EDEMA: RIGHT HEART FAILURE

ASCITES: RIGHT HEART FAILUREPMI: LEFT HEART FAILUREPulsus alternans is a physical finding with arterial pulse waveform showing alternating strong and weak beats.[1] It is almost always indicative of left ventricular systolic impairment, and carries a poor prognosis.Left heart failure can be due to systolic (decline in EF of LV) or diastolic (disruption of normal filling of LV) dysfunction. The causes of systolic and diastolic dysfunction are discussed in question 5.

The classic manifestation of left heart failure is dyspnea. Early in the disease, dyspnea is seen primarily on exertion. However, as the disease progresses, pulmonary congestion is increased in the supine position leading to orthopnea and paroxysmal nocturnal dyspnea. Orthopnea is the sensation of shortness of breath when lying flat and relieved on sitting up. Paroxysmal nocturnal dyspnea is the sudden onset of severe shortness of breath while lying down sleeping, forcing the patient to sit or stand to get relief. At the extreme, the patient may develop pulmonary edema. This is manifested by marked shortness of breath even when upright. Associated symptoms may include a sense of chest tightness, anxiety, diaphoresis, and pallor. Pulmonary edema may also trigger a cough. This can be accompanied by production of frothy sputum that may be blood tinged. In the presence of increasing venous congestion and right heart failure, patients often notice dependent edema, especially in the distal extremities. Passive congestion of the liver can cause right upper quadrant discomfort and a sense of abdominal bloating, nausea, and loss of appetite. Patients may also notice daytime oliguria and increasing nocturia. Right heart failure is characterized by a decrease in the right ventricle pumping function. Most cases of right heart failure stem from a disorder that leads to pulmonary hypertension, which in turn creates a pressure load on the ventricle. Examples of disorders leading to isolated right ventricular failure include mitral stenosis, pulmonary embolism, and chronic lung disease. However, the most common cause of right ventricular failure is left ventricular failure. As the left ventricle fails and pulmonary arterial pressure rises, the pressure load on the right ventricle is increased. Ultimately dilation of the right ventricle occurs, leading to failure. This in turn leads to an increase in systemic venous pressures. Rarely, disease affecting the right ventricle alone, such as a right ventricular infarction or impairment of the right ventricular musculature, can lead to right ventricular failure in the absence of pulmonary hypertension.

Clinical Manifestations:

Palpation of the heart can reveal the sustained left ventricular heave. Careful auscultation of the heart can reveal characteristic heart sounds and murmurs.

S3 - over the apex is a sign of a dilated, poorly contractile left ventricle and is highly predictive of the presence of heart failure

S4 is associated with a noncompliant left ventricle and may suggest left ventricular hypertrophy but is not reliable for distinguishing diastolic from systolic dysfunction.

crescendo-decrescendo systolic murmur, especially located along the left upper sternal border, should lead to consideration of occult aortic stenosis, which can lead to LV hypertrophy.

blowing systolic murmur radiating from the apex toward the axilla suggests mitral regurgitation. This may be a cause of CHF or occur as the left ventricle dilates and enlarges the mitral ring.

Right ventricle dilatation can lead to the development of tricuspid regurgitation manifested as a holosystolic murmur along the left lower sternal border and a prominent jugular venous pulse that peaks during systole (v-wave).

right-sided heart failure can cause hepatomegaly, which will feel mildly tender on palpation.

Pitting edema is common in the presence of heart failure. This generally is located in the dependent areas of the body such as the ankles and feet; however, in patients who are bedbound, it may best be identified over the sacrum.

7. Describe the natural history of untreated CHF

Typically the process of heart failure begins with an injury or disruption to the normal intricate balance of structures that contribute to normal heart functioning. This can include direct damage to the cardiac muscle (myocardial ischemia, myocarditis), obstruction to outflow (valvular disease, hypertension), or problems with filling (pulmonary hypertension, left ventricular hypertrophy). In response to this initial injury, there is active remodeling of cardiac muscle often with thickening or lengthening of the myocardial muscle. This is accompanied by infiltration of inflammatory cells and deposition of fibrin. Systemically, the changes in perfusion pressures and hemodynamics lead to a host of hormonal responses, including activation of the renal angiotensin-aldosterone system and the sympathetic nervous system. This will lead to systolic and/or diastolic dysfunction. The weakened heart muscle may not be able to supply enough blood to the kidneys, which begin to lose their normal ability to regulate sodium and water excretion. Diminished kidney function can cause increased retention of fluid. Lungs may become congested with fluid and the person's ability to exercise is decreased. Fluid may likewise accumulate in the liver, impairing its ability to rid the body of toxins and produce essential proteins. Intestines may become less efficient in absorbing nutrients and medicines. Over time, untreated, worsening congestive heart failure will affect virtually every organ in the body.

8. Discuss guidelines for treatment of CHF including systolic and diastolic function

The management of chronic heart failure focuses on improving function and reducing long-term mortality. A number of drugs have been demonstrated to prolong life expectancy and improve function. ACE inhibitors should be the first-line drug used in all patients with heart failure. ACE inhibitors modulate the renin-angiotensin system, reduce afterload, and can facilitate ventricular remodeling. Beta blockers, specifically bisoprolol, carvedilol, and metoprolol, have also been demonstrated to reduce mortality in heart failure. Beta blockade reduces the workload of the heart, decreases the impact of sympathetic nervous system stimulation, and reduces blood pressure. Diuretics have not been shown to prolong life but are quite effective in reducing symptoms and reducing hospitalizations. Aldosterone inhibition using spironolactone or eplerenone can be a useful adjunct in late-stage heart failure in symptomatic patients resistant to loop diuretics. These agents have been demonstrated to reduce death and hospitalizations. Digoxin has been demonstrated to improve symptoms of fluid overload and reduce the frequency of hospitalization, although there has not been any demonstrated impact on mortality. Digoxin is particularly useful for rate control when atrial fibrillation is present. Lifestyle modification to reduce factors that exacerbate heart failure or independently impair cardiac function play an important role in disease management. Ultimately, heart transplantation can be an option for patients with end-stage heart

failure. It is reserved for patients with intractable functional Class III or IV CHF who have little likelihood of survival during the next 6 to 12 months.

9. Describe the use of BNP measurement in the evaluation of CHF

Brain natriuretic peptide, now known as B-type natriuretic peptide, is secreted by the ventricles of the heart in response to excessive stretching. BNP levels in the blood are used for screening, diagnosis and prognosis of acute congestive heart failure. However, there is no level of BNP that perfectly separates patients with and without heart failure. For patients with CHF, BNP values will generally be above 100 pg per milliliter. There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive. Values above 500 pg/mL are generally considered to be positive. The plasma concentrations of BNP are also typically increased in patients with left ventricular dysfunction.

10. Test for LV Function and CHF

Regardless of the specific symptom complex, severity of CHF is commonly gauged using the New York Heart Association (NYHA) Functional Classification of Congestive Heart Failure (Table 28.2).

On examination, physical signs are largely related to the manifestations of venous congestion and ventricular dysfunction. On inspection, patients in pulmonary edema typically are sitting upright and are in visible respiratory distress. Tachypnea and tachycardia frequently are seen. An irregularly irregular pulse suggests atrial fibrillation. Hypertension at the time of presentation is unusual if there is significant systolic dysfunction because of the inability of the ventricle to generate high pressures. Accordingly, the presence of hypertension at the time of initial evaluation is associated with the presence of diastolic dysfunction as the etiology in close to two thirds of patients.

Inspection of the neck can reveal jugular venous distension, a manifestation of right-sided failure. Elevation of the jugular venous pulse to greater than 3 cm above the sternal angle has a 60% sensitivity and near 80% specificity for increased atrial filling pressure. A positive hepatojugular reflux, persistent elevation of the jugular venous pulse with firm pressure over the liver, is more specific (94%) for the presence for congestive heart failure. Lung examination may reveal basilar rales, rhonchi, and dullness at the bases in the presence of left ventricular failure.

Table 28.2 New York Heart Association functional classification of congestive heart failure

Class Description

I Symptoms with greater than ordinary activity (i.e., no impairment)

II Symptoms with ordinary activity (i.e., mild impairment)

III Symptoms with minimal activity, asymptomatic at rest (i.e., significant impairment)

IV Symptoms at rest (i.e., severe impairment)

Palpation of the heart can reveal the sustained left ventricular heave of left ventricular hypertrophy, the slight tapping sensation of the ventricle in the presence of mitral stenosis or the diffuse, displaced Part of Maximal Impulse (PMI) of a dilated left ventricle. Careful auscultation of the heart can reveal

characteristic heart sounds and murmurs. An S3 over the apex is a sign of a dilated, poorly contractile left ventricle and is highly predictive of the presence of heart failure, but is only present in half of patients. An S4 is associated with a noncompliant left ventricle and may suggest left ventricular hypertrophy but is not reliable for distinguishing diastolic from systolic dysfunction. A crescendo-decrescendo systolic murmur, especially located along the left upper sternal border, should lead to consideration of occult aortic stenosis. A blowing systolic murmur radiating from the apex toward the axilla suggests mitral regurgitation. This may be a cause of CHF or occur as the left ventricle dilates and enlarges the mitral ring. Dilation of the right ventricle can lead to the development of tricuspid regurgitation manifested as a holosystolic murmur along the left lower sternal border and a prominent jugular venous pulse that peaks during systole (v-wave).

In the presence of right-sided heart failure, hepatomegaly can develop. Typically this is mildly tender to palpation. In the presence of tricuspid regurgitation, pulsations can be felt. Pitting edema is common in the presence of heart failure. This generally is located in the dependent areas of the body such as the ankles and feet; however, in patients who are bedbound, it may best be identified over the sacrum.

11. Differential diagnosis for hyponatremia

Hypotonic hyponatremia is a common type of sodium disorder. When hypotonic hyponatremia is present, volume status needs to be assessed to determine its cause and to choose the appropriate therapy. Hypotonic hyponatremia may occur in association with hypovolemia (for example, after gastrointestinal losses), with euvolemia (for example, syndrome of inappropriate antidiuretic hormone [SIADH]) or with hypervolemia (for example, congestive heart failure) (Table 86.2).

Hypovolemic hyponatremia occurs when total body Na+ is depleted in relation to total body water (TBW). This can occur with either renal or nonrenal Na+ loss. Nonrenal Na+ loss is common among ill and hospitalized patients and can occur with diarrhea, vomiting, or bleeding. Renal losses occur in response to diuretics, in uncontrolled diabetes mellitus, and in the rather uncommon syndromes of renal salt wasting. In each of these settings, hypovolemia induces the release of ADH, which promotes the reabsorption of water from urine. Hyponatremia then occurs as a result of the loss of Na+ and the retention of water. Urinary electrolytes may be useful in distinguishing between renal and nonrenal losses. With renal losses, urinary Na+ usually exceeds 20 mEq/L. In contrast, with nonrenal Na+ loss, urinary Na+ usually is less than 20 mEq/L.

In euvolemic hyponatremia, volume status is normal and hyponatremia is due to an excess of water. The most common cause of euvolemic hyponatremia is SIADH (Chapter 68). Common causes of SIADH include cancers, pulmonary disease, intracranial disease, and medications. Urinary Na+ typically exceeds 20 mEq/L and the urine is inappropriately concentrated (Uosm >100 mOsm/kg) for the degree of plasma hypo-osmolality. Another two causes of euvolemic hyponatremia are severe hypothyroidism and adrenal insufficiency (more common in primary than in secondary adrenal insufficiency).

Table 86.2 Causes of hyponatremia

Decreased ECV Normal ECV Increased ECV

Renal losses SIADH Nephrotic

Diuretics   Congestive heart failure

Salt-losing nephropathy Hypothyroidism Cirrhosis

Hypoaldosteronism    

Gastrointestinal losses  Diarrhea  Vomiting

   

Skin losses  Fever, burns

   

ECV, extracellular volume; SIADH, syndrome of inappropriate antidiuretic hormone.

Hyponatremia also may occur with expanded extracellular fluid in congestive heart failure, cirrhosis, and nephrotic syndrome. These conditions are characterized by decreased effective circulatory volume despite a higher than normal TBW. The decrease in effective circulatory volume results in secretion of ADH, which, in turn, leads to water retention and dilutional hyponatremia. In these settings, hyponatremia usually serves as a marker of the severity of the underlying disease and occurs only when severe disease is present. For example, the plasma sodium might fall to about 130 mEq/L when the cardiac index is 1.5 L/min/m2 or less. In such conditions, urine Na+ concentrations are less than 20 mEq/L because of avid Na+

reabsorption

12. Diagnosis of hyponatremia

INTRODUCTION   —   In virtually all patients, hyponatremia reflects water retention due to an inability to

match water excretion with water ingestion. In most patients who do not have advanced renal failure, this

defect represents the syndrome of inappropriate ADH secretion (SIADH), one of the hypovolemic states,

or hyperglycemia. Although the definition may vary among different clinical laboratories, hyponatremia

is commonly defined as a serum sodium concentration ≤135 meq/L [ 1 ].

DIAGNOSIS   —   The diagnostic approach to the patient with hyponatremia consists of a directed history

and physical examination, appropriate laboratory tests, and, in selected patients, assessing the response

to volume expansion with isotonic saline.

History and physical examination   —   The history and physical examination in hyponatremic patients

should be directed toward identification of findings that are typical of the particular causes of

hyponatremia ( show table 1 ) [ 2-4 ].

These include:

• A history of fluid loss (eg, vomiting, diarrhea, diuretic therapy) and, on examination, signs of

extracellular volume depletion, such as decreased skin turgor and a low jugular venous pressure.

• Signs of peripheral edema and/or ascites, which can be due to heart failure, cirrhosis, or renal failure.

• A history consistent with one of the causes of SIADH, such as small cell carcinoma or central nervous

system disease.

• Symptoms and signs suggestive of adrenal insufficiency or hypothyroidism.

Although the history and physical examination often provide important clues to the cause of

hyponatremia, identification of subtle degrees of volume depletion or edema may be difficult [ 4 ]. As a

result, laboratory testing is almost always required to establish the diagnosis.

Laboratory tests   —   Three laboratory tests provide important initial information in the differential

diagnosis of hyponatremia [2]:

• Plasma osmolality

• Urine osmolality

• Urine sodium concentration

Plasma osmolality   —   The plasma osmolality, which normally ranges from 275 to 290 mosmol/kg, is

reduced in most hyponatremic patients, because it is primarily determined by the plasma sodium

concentration and accompanying anions.

In some cases, however, the plasma osmolality is either normal or elevated.

• Hyponatremia with a normal plasma osmolality may be due to hyperlipidemia or hyperproteinemia

(called pseudohyponatremia since it represents a laboratory artifact), or it may follow the infusion

of sucrose and maltose-containing IgG formulations or the absorption of isotonic glycine during

urological or gynecological procedures.

• Hyponatremia with a high plasma osmolality may be seen with hyperglycemia or the administration of

hypertonic mannitol, both of which induce osmotic water movement out of the cells and lower

the plasma sodium concentration by dilution [2,5-8]. However, this effect is at least in part

counteracted by the osmotic diuresis that typically occurs in such patients. By causing water loss

in excess of sodium and potassium, the osmotic diuresis can raise the plasma sodium

concentration to normal or even high values.

• Renal failure presents a different problem since the blood urea nitrogen (BUN) is elevated but urea is

an ineffective osmole. The effective plasma osmolality is calculated from the measured value

minus the BUN/2.8 or minus the blood urea if measured in mmol/L. Because of the elevation in

BUN, the plasma osmolality may be normal or even elevated, but the effective osmolality is

reduced. As a result, these patients have true hyponatremia.

In patients with hyperlipidemia or hyperproteinemia who present with a low serum sodium concentration

but a normal plasma osmolality (called pseudohyponatremia), ion-selective electrodes will reveal a

normal serum sodium concentration if an instrument employing direct potentiometry is used. Many

laboratory analyzers that measure sodium with ion-selective electrodes utilize indirect potentiometry in

which the serum or plasma sample is diluted before measurement; these will report a low sodium

concentration.

Urine osmolality   —   In patients with hyponatremia and a low plasma osmolality, the urine osmolality can

be used to distinguish between impaired water excretion (which is present in almost all cases) and

primary polydipsia, in which water excretion is normal but intake is so high that it exceeds excretory

capacity.

The normal response to hyponatremia (which is maintained in primary polydipsia) is to completely

suppress ADH secretion, resulting in the excretion of a maximally dilute urine with an osmolality below

100 mosmol/kg and a specific gravity ≤1.003. Values above this level indicate an inability to normally

excrete free water, most commonly because of continued secretion of ADH. Most hyponatremic patients

have a relatively marked impairment in urinary dilution that is sufficient to maintain the urine osmolality

at 300 mosmol/kg or greater.

There are two hyponatremic disorders other than primary polydipsia in which the urine osmolality may be

below 100 mosmol/kg:

• Malnutrition, described primarily in beer drinkers (called beer drinkers potomania), in which dietary

solute intake (sodium, potassium, protein) and therefore solute excretion is so low that the rate of

water excretion is markedly diminished even though urinary dilution is intact.

• Reset osmostat after a water load appropriately suppresses ADH release. The major clinical clue to the

presence of this disorder is a moderately reduced plasma sodium concentration (usually between

125 and 135 meq/L) that is stable on multiple measurements.

The urine osmolality may be below 100 mosmol/kg if it is measured after the reason for water retention

has been eliminated (eg following volume expansion with isotonic saline in a patient with hypovolemic

hyponatremia); in this case, the low urine osmolality heralds the spontaneous and rapid correction of

hyponatremia.

Urine sodium concentration   —   In patients with hyponatremia, hypoosmolality, and an inappropriately

concentrated urine, the urine sodium concentration can be used to distinguish between hyponatremia

caused by a decreased effective arterial blood volume and euvolemic hyponatremia [ 2 ]:

• The urine sodium concentration is usually below 25 meq/L in hypovolemia, unless there is renal salt-

wasting, due most often to diuretic therapy and infrequently to adrenal insufficiency or cerebral

salt-wasting).

• The urine sodium concentration is usually above 40 meq/L in patients with the SIADH who are

normovolemic and whose rate of sodium excretion is determined by sodium intake, as it is in

normal subjects [10-12].

As another example, suppose that the initial urine sodium concentration is 35 meq/L, an intermediate

value. Serial monitoring of the urine sodium concentration and urine osmolality in response to the

administration of isotonic saline can help clarify the diagnosis:

• If the patient is hypovolemic, isotonic saline should suppress the hypovolemic stimulus to ADH

release, promoting the excretion of dilute urine and rapid correction of the hyponatremia.

• If the patient has SIADH, ADH release occurs independently of the volume status, so the urine

osmolality remains high, whereas sodium excretion is promoted by volume expansion. As result,

the urine sodium concentration rises above 40 mEq/L.

Acid-base and potassium balance   —   Evaluation of acid-base and potassium balance may be helpful in

selected hyponatremic patients in whom the diagnosis is not apparent. As examples, metabolic alkalosis

and hypokalemia suggest diuretic use or vomiting, metabolic acidosis and hypokalemia suggest diarrhea

or laxative abuse, and metabolic acidosis and hyperkalemia suggest adrenal insufficiency [ 2 ].

13. Treatment of hyponatremia

METHODS OF RAISING THE PLASMA SODIUM   —   The plasma sodium concentration can be raised

in hyponatremic patients by restricting water intake, by giving salt , or by giving vasopressin receptor

antagonists [ 1,25 ]. The choice of therapy is primarily governed by the cause and severity of the

hyponatremia. In addition, hormone replacement will correct the hyponatremia in patients with adrenal

insufficiency or hypothyroidism.

Water restriction   —   Water restriction to below the level of output is the primary therapy for

hyponatremia in edematous states (such as heart failure and cirrhosis), SIADH, primary polydipsia, and

advanced renal failure. Hyponatremia develops gradually in these settings and is rarely symptomatic.

Restriction to 50 to 60 percent of daily fluid requirements may be required to achieve the goal of inducing

a negative water balance

Sodium chloride administration   —   Salt , usually as isotonic saline or increased dietary salt, is given to

patients with true volume depletion, adrenal insufficiency, and in some cases of SIADH. Salt therapy is

generally contraindicated in edematous patients (eg, heart failure, cirrhosis, renal failure) since it will

lead to exacerbation of the edema

Hypertonic saline is generally recommended only for patients with symptomatic or severe hyponatremia.

The degree to which isotonic saline will raise the plasma sodium concentration in hyponatremic patients

varies with the solution used and with the cause of the hyponatremia.

Vasopressin receptor antagonists   —   An alternative or possible addition to saline administration or water

restriction in patients with hyponatremia is the use of ADH receptor antagonists. There are multiple

receptors for vasopressin (ADH): the V1a, V1b, and V2 receptors. The V2 receptors primarily mediate

the antidiuretic response, while V1a and V1b receptors principally cause vasoconstriction and mediate

adrenocorticotropin release, respectively [15,29,30].

The vasopressin receptor antagonists produce a selective water diuresis without affecting sodium and

potassium excretion. The ensuing loss of free water will tend to correct the hyponatremia. However, thirst

increases significantly with these agents, which may limit the rise in serum sodium [ 24 ].

Effect of potassium — It is important to appreciate that potassium is as osmotically active as sodium and

that giving potassium can raise the plasma sodium concentration and osmolality in a hyponatremic

subject [27,28,32,33]. As most of the excess potassium goes into the cells, electroneutrality is maintained

in one of three ways, each of which will raise the plasma sodium concentration:

• Intracellular sodium moves into the extracellular fluid.

• Extracellular chloride moves into the cells with potassium; the increase in cell osmolality promotes free

water entry into the cells.

• Intracellular hydrogen moves into the extracellular fluid. These hydrogen ions are buffered by

extracellular bicarbonate and to a much lesser degree plasma proteins. This buffering renders the

hydrogen ions osmotically inactive; the ensuing fall in extracellular osmolality leads to water

movement into the cells.

14. Describe the pathophysiological basis for the use of aldosterone antagonists in CHF

Heart failure is a clinical syndrome characterized by the functional inability of the ventricle to meet the metabolic demands of the body. Renal hypoperfusion occurs as a result of reduced cardiac output, resulting in the activation of the renin–angiotensin–aldosterone system, which compensates for the hypoperfusion. However, this contributes to the pathology of the disease by, among other actions, increasing the release of aldosterone. Aldosterone has been shown to cause coronary inflammation, cardiac hypertrophy, myocardial fibrosis, ventricular arrhythmias, and ischemic and necrotic lesions. There are currently two aldosterone antagonists commercially available in the United States, spironolactone and eplerenone. Spironolactone is a nonselective aldosterone antagonist, and eplerenone is selective to the aldosterone receptor. Although numerous clinical trials have evaluated the efficacy of each drug, no studies have directly compared spironolactone and eplerenone. Both have been shown to

improve morbidity and mortality in patients with advanced heart failure. Adverse effects of both spironolactone and eplerenone include potentially life-threatening hyperkalemia, which can be induced by renal insufficiency, diabetes mellitus, advanced heart failure, advanced age, and concurrent drug therapy.

Conclusion: Spironolactone and eplerenone are life-saving agents in patients with advanced heart failure and may benefit patients with mild heart failure. Potassium and renal function must be routinely assessed to minimize the risk of life-threatening hyperkalemia.

Treatment: change diuretics, increase diuretics

Furosimide: risk= HYPOKALMEMIAMANNITOL= ONLY FOR CEREBRAL TRAUMA PATIENTSSPIRONOLACTONE-RISK IS ARRTHYMIADUCHENNEHypoxic: activate receptorDiasystolic is less severeBlack males: HTN and CHF

Democlocline

MUST BE GIVEN SLOWLY: To high sodium- coma, brain edema, centropontinemyelolysis