Metabolism diseases affecting

Several metabolic diseases affect kidney function leading to chronic complications including osteoporosis, hypertension, anania, and electrolyte abnormalities. 

Diseases affecting skeletal muscle are not always primary diseases of muscle, and it is necessary first to determine whether a particular disorder is a primary disease of muscle, is neurogenic in origin, is an inflammatory disorder, or results from vascular insufficiency. A primary disease of muscle is one in which the skeletal muscle fibers are the primary target of the disease. Neurogenic disorders are those in which weakness, atrophy, or abnormal activity arises as a result of pathological processes in the peripheral or central nervous system. Inflammatory disorders may result in T-cell mediated muscle damage and are often associated with viral infections. Vascular insufficiency as a result of occlusion in any part of the muscle vasculature can cause severe disorders of muscle, especially in terms of pain, metabolic insufficiency, and weakness. 

The metabolic myopathies are exceptionally complex. Mitochondrial disorders are usually multisystem disorders, in which metabolic dysfunction affects muscle, liver, CNS, and special senses (especially vision) in almost any combination. There is evidence that some forms of mitochondrial disease are inherited, and the preponderance of maternal rather than paternal inheritance is consistent with an abnormality in the mitochondrial genome because almost all (and perhaps all) mitochondria are derived from the ovum. 

Table 48-10. Some metabolic and genetic diseases affecting bone and cartilage.

The role of fatty acids as oxidizable fuels for brain metabolism is negligible, but ketone bodies, derived from fatty acid oxidation, can be utilized, particularly in the neonatal period. Diseases of carbohydrate and fatty acid metabolism may affect the brain directly or indirectly [1,10]. 

Extrapolation of the result to the patient population (especially children or patients with hepatic or renal diseases affecting drug metabolism)... 

Other infectious diseases, such as pneumonia, typhoid fever, and erysipelas, may cause delirium, often associated with high fever. The temperature rise (fever) itself alters brain metabolism by affecting different enzyme systems differently. In addition toxic substances produced by infective agents may directly affect metabolic processes. 

While cotinine functions fairly well as a marker of nicotine intake, it is not perfect due to individual variation in metalxtlism as discussed previously. As described earlier in this chapter, cotinine metabolism is affected by factors such as race, gender, age, genetic variation in the liver enzyme CYP2A6, and/or by the presence of pregnancy, liver or kidney disease. Another limitation to the use of cotinine is that, given an average half-life of 16 h, cotinine levels reflect relatively short-term exposure to tobacco (that is, over the past 3 days). 

Diseases of muscle are usually classified as muscular dystrophies, inflammatory or congenital myopathies, metabolic disorders affecting the muscle, and neurological diseases affecting the innervation of the muscle (so-called motor neuron diseases). In the past, the energy metabolism of some muscular diseases... 

Diabetes mellitus is a very common metabolic disease that is caused by absolute or relative insulin deficiency. The lack of this peptide hormone (see p. 76) mainly affects carbohydrate and lipid metabolism. Diabetes mellitus occurs in two forms. In type 1 diabetes (insulin-dependent diabetes mellitus, IDDM), the insulin-forming cells are destroyed in young individuals by an autoimmune reaction. The less severe type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM) usually has its first onset in elderly individuals. The causes have not yet been explained in detail in this type. 

Familial LCAT deficiency, an inborn error of metabolism that affects the levels of plasma cholesteryl esters, was recently discovered in Scandinavia (G7, G8, G9, GIO, Gll, N4). Patients with this disease have... 

Disease/pathological conditions. Disposition of chemicals is potentially altered by disease and hence toxicity. Generalization, however, is difficult as the effects are unpredictable. Thus liver disease may decrease metabolism, but this depends on type of disease and particular pathway of metabolism. Disease in one organ may affect the response of another, for example, chronic renal disease decreases hepatic cytochrome P-450. 

Whereas many metabolic defects affect only a small number of individuals, emotional illnesses including depression, schizophrenia, and other affective disorders at one time or another afflict a large fraction of the population. Autism affects thousands of children.1055 Parkinson disease and Alzheimer disease are just two of a number of degenerative neural diseases attacking older people. Less commonly, young persons contact multiple sclerosis and muscular dystrophy, which is often a disease of neuromuscular junctions. 

When mixing a compound to the diet, pilot experiments should be conducted to verify that food intake is not affected by the change of palatability in the diet. This is counterintuitive, as a compound reducing food intake might be considered a benefit for a metabolic disease. However, unspecific effects on metabolism due to diet unpatability should be tested and excluded early on. 

Not all calcium present in the diet is absorbed by the small intestine and mechanisms are present to ensure only amounts appropriate to body needs are absorbed. These processes are complex and involve the interaction of special transport protein, vitamin D and parathormone. Thus, abnormalities of calcium metabolism may result from many different disease processes. Diseases affecting the bowel may prevent normal absorption, diseases of the parathyroid gland may result in inappropriate levels of parathormone for calcium requirement and a nutritionally inadequate diet may cause vitamin D deficiency with consequent disordered calcium absorption. 

Subacute Zinc Defiency Subacute zinc deficiency is the major clinical zinc deficiency syndrome in the U.S. Based upon a national survey of smell function performed in 1980, estimates suggest that this syndrome may affect as many as 4 million people (59). The etiology of subacute zinc deficiency is related to a variety of disorders which do not, at first glance, appear to have any specific relationship to a metabolic disease process (Table III) (60). Indeed, the mechanisms by which a viral illness, head Injury, surgical procedures, or allergic rhinitis may produce lowered body zinc levels are still unknown. In addition, to complicate this problem further, the onset of this syndrome can occur relatively quickly, over days, or more slowly, over... 

Beriberi (infantile and adult) and Wernicke s encephalopathy (WE) are clinical manifestations attributed to thiamine deficiency. Beriberi is characterized by peripheral neuropathy including sensory, motor, and reflex functions affecting the distal segments of limbs more severely than proximal ones (TanPhaichitr, 1985). WE is a metabolic disease due to thiamine deficiency and is characterized by lesions in the thalamus, hypothalamus (including mammillary nuclei), and cerebellum (Victor et al., 1971 Harper and Butterworth, 1997). 

Similarly the state of health of a person can affect the way they handle a drug or other chemical substance by altering, for example, their metabolic capability or kidney function. Serious diseases affecting the function of a particular organ will have major effects if that organ is involved in the metabolism or excretion of the drug. 

The clinical course can be unfavourably affected by various risk factors (e.g. race, gender, advanced age, immune status, genetics) as well as by alcohol abuse (275, 337, 363), toxins, coinfections and chemicals. Conversely, the course and prognosis of HBV, HDV and HIV infections as well as of metabolic diseases (e.g. porphyria cutanea tarda, ai-antitrypsin deficiency) can deteriorate as a result of hepatitis C. 

Genetic disease Vitamin D metabolism is adversely affected in a rare genetic disease that results in impairment of the conversion of vitamin Dj to the hormonally active form. The disease affects l-hydroJ(ylase an enzyme of the kidney. 

The colon contains both aerobic and anaerobic micro-organisms that may metabolize some drugs. Crohn s disease affects the colon and thickens the bowel wall. The microflora may also become more anaerobic. Absorption of clindamycin and propranolol are increased, whereas other drugs have reduced absorption with this disease (Rubinstein et al., 1988)... 

Because the liver is a major processor of dietary and endogenous carbohydrates, liver disease affects carbohydrate metabolism in a variety of ways (see Chapter 25). However, none of the conventional modes of evaluating carbohydrate metabolism have value in the diagnosis of liver disease. Because the liver is the major site of both glycogen storage and gluconeogenesis, hypoglycemia is a common complication in certain liver diseases, particularly Reye s syndrome, fulminant hepatic failure, advanced cirrhosis, and hepatocellular carcinoma. 

Liver, Iddney, and thyroid disease affect the secretion and metabolism of the adrenal steroids. Other factors affecting these processes mclude stress, age, estrogen therapy, nutrition, and drugs. 

Question Drug C has a total clearance of 7 L/hour, a volume of distribution of 420 L, and a rate of excretion unchanged of 80%. Will drug levels of this drug be affected by induction and/or inhibition of lever metabolism, compromised liver blood flow due to cardiovascular disease, or the presence of liver disease Would renal disease affect levels of drug C ... 

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