Decompensation metabolic

Heart failure patients exist in one of two clinical states. When a patient s volume status and symptoms are stable, their HF condition is said to be compensated. In situations of volume overload or other worsening symptoms, the patient is considered decompensated. Acute decompensation can be precipitated by numerous etiologies that can be grouped into cardiac, metabolic, or patient-related causes (Table 3-3).5... 

It is important for the clinician to identify the cause(s) of AHF in order to maximize treatment efficacy and reduce future disease exacerbations. Cardiovascular, metabolic, and lifestyle factors can all precipitate AHF. The most common precipitating factors for acute decompensation and how they contribute pathophysiologically are listed in Table 3-3. 

Brain edema, often associated with increased intracranial pressure, may accompany the acute phase of metabolic decompensation in the aminoacidurias 671... 

Imbalances of brain amino acids may hinder the synthesis of brain lipids, leading to a diminution in the rate of myelin formation. Decreases of lipids, proteolipids and cerebrosides (Ch. 3) have been noted in several of these syndromes, e.g. maple syrup urine disease, when intra-myelinic edema is a prominent finding, particularly during the acute phase of metabolic decompensation [9]. Pathological changes in brain myelin are common, especially in infants who die early in life. The fundamental... 

Effective treatment of maple syrup urine disease involves the restriction of dietary branched-chain amino acids. Long-term treatment entails the dietary restriction of the BCAAs. This is accomplished by administration of a special formula from which these amino acids are removed. The outlook for intellectual development is favorable in youngsters in whom diagnosis is made early and who do not suffer recurrent, severe episodes of metabolic decompensation [17]. 

Jan,W., Zimmerman, R. A.,Wang, Z. J., Berry, G. T., Kaplan, P. B. and Kaye, E. M. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 45 393-399,2003. 

Gynecomastia Gynecomastia may develop and appears to be related to dosage and duration of therapy. It is normally reversible when therapy is discontinued. Reversible hyperchloremic metabolic acidosis Reversible hyperchloremic metabolic acidosis, usually in association with hyperkalemia, occurs in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function. 

Hepatic function impairment Zaleplon is metabolized primarily by the liver and undergoes significant presystemic metabolism. Consequently, the oral clearance of zaleplon was reduced by 70% and 87% in compensated and decompensated cirrhotic patients, respectively. 

Urine is collected from patients suspected to have an organic acidemia preferably during an acute metabolic decompensation. As this is often not possible, an early morning specimen should be collected. The sample should be sent frozen and without preservatives. 

In obtaining the clinical history, particular attention should be paid to situations that may provoke episodic symptoms. Skipping meals, mild viral illnesses, and exercise are examples of metabolic stressors that may result in symptomatic decompensation. Importantly, results of... 

OTC deficiency is the most common urea cycle defect.As it is X linked, affected boys typically have severe disease with neonatal presentation as described in this chapter. The disease in women who carry an OTC mutation on one X chromosome ranges from severe early-onset disease to complete absence of symptoms. Furthermore, affected women may decompensate in the context of a metabolic stress such as an infection or following parturition. OTC-deficient patients have low plasma citrulline and high urine orotic acid. Confirmation of the diagnosis requires mutation analysis or a liver biopsy for enzymology. The carrier status of women is most accurately determined by mutation analysis. 

Why might infection precipitate metabolic decompensation in an individual with HMG-CoA lyase deficiency ... 

The patient was suffering from newly diagnosed type 1 diabetes and one of its common metabolic decompensations, diabetic ketoacidosis (DKA). 

Newly diagnosed patients with type 1 diabetes may present with acute metabolic decompensations, ketone production, and metabolic acidosis, a condition known as diabetic ketoacidosis (DKA).Although (J-cell destruction occurs gradually, acute physical or emotional stress can acutely create a demand for increased insulin production. 

Depolarization Local depolarization caused by focal hypoxia decompensates already threatened metabolism in penumbra and propagates ischemic damage... 

A limited number of small single-dose studies have demonstrated that morphine metabolism is impaired in patients with decompensated cirrhosis, and half-life can be doubled. Information on multiple morphine doses in cirrhotic patients is lacking, but because of the demonstrated prolonged half-life in single-dose studies, accumulation could occur, and an increased dosing interval of approximately twofold is recommended in some reports. 

Overall, clinical trials have shown that the metabolism of single doses of morphine is significantly impaired in patients with decompensated cirrhosis, bnt possibly not in those with compensated cirrhosis. 

NSAIDs should be avoided in decompensated cirrhotic patients because of the potential for impaired metabolism and increases in the level of unbound drug due to low albumin and high bilirubin, but more importantly NSAIDs should be avoided because of their unfavourable side-effect profile (see details in Patient 3). 

Advice as for Patient 3, but greater care needs to be taken because increased accumulation is likely to occur as the metabolic capacity of the liver is affected in decompensated cirrhosis. Doses at the higher end of the range given are unlikely to be tolerated. 

Cyclizine, prochlorperazine and promethazine can be used with caution in patients whose metabolic and synthetic function is unaffected, but must be avoided in encephalopathic patients or in those with cirrhosis who may decompensate. 

Despite cirrhosis, this patient is maintaining good hepatocyte function (normal albumin and bilirubin, mildly raised INR) and the metabolic and excretory capacity of the liver should not be significantly reduced. The patient has portal hypertension, so blood flow to the liver will be impaired, which will reduce the first-pass metabolism of highly extracted drugs (extraction ratio >0.7). This will result in greater bioavailability of oral doses of these drugs. It is important to note that the patient could rapidly deteriorate into a state of decompensation where liver function would be markedly affected. 

HRT (oral and transdermal) should not be initiated or continued in patients with decompensated cirrhosis. The hepatocyte damage is irreversible and can only worsen over time. The significant reduction in metabolic capacity and reduction in hepatic blood flow will lead to drug accumulation, with consequent increased risk of hepatotoxicity. There is also the potential to worsen the cholestatic picture in this patient, who is already profoundly jaundiced. 

It is thought that progesterone derivatives have the least effect on liver metabolism and provide a reliable assurance against pregnancy. Hepatic disturbance is not considered a contraindication to progesterone therapy [2], but in practice the method cannot be recommended in active viral hepatitis or severe decompensated cirrhosis [4], Viral hepatitis carriers can use the POC methods in any circumstance [30]. When patients with acute hepatitis recover fully and LFTs have returned to normal, the full spectrum of contraceptive choices can be considered however, such patients should be monitored carefully during the initiation period [2]. 

The liver has a large metabolic reserve, and it is only when disease becomes decompensated that... 

Ascites and oedema are also found in severe hepatic diseases, pointing to serious disorders in the water and electrolyte metabolism. These complications are signs of decompensation in fiver cirrhosis or chronic liver insufficiency. At the same time, pleural effusion may also be evident. Cirrhosis-related pleural effusion without concomitant ascites has been described as a rarity. (see chapter 16)... 

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