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Showing posts from February, 2011

ARDS-Acute Respiratory Distress Syndrome-Causes-Signs-Symptoms

Definition  ARDS (Acute Respiratory Distress Syndrome) follows lung injury And Characterized by an inadequate expansion of lungs and hypoxemia ( inadequate oxygenation of Blood). Causes: 1. Diffused alveolar capillary damage 2. Alveolar epithelial damage. Signs and Symptoms: Respiratory insufficiency  Cyanosis Arterial hypoxemia which is refractory to oxygen therapy Multi-organ failure ( eg. liver, kidney, heart etc ) Pathogenesis: Damage to either alveolar epithelium  or Vascular endothelium      2.  Imbalance between pro-inflammatory and anti-inflammatory factors  Vascular injury causes An increase in vascular permeability  Alveolar flooding loss of diffusion capacity ( gases fail to diffuse across the alveolar membrane ) Surfactants abnormality.  ( due to damage of type II pneumocytes ) IL 8 ( Interleukine 8 ) is synthesized at the site of vascular endothelial or alveolar epithelial injury which causes chemotaxis of leukocytes (neutrophils).  IL 1 and T

DRUG INDUCED HEPATOTOXICITY / Liver Damage- Causes - Risk Factors - DILI -

Hepatotoxicity:- Hepatotoxicity implies chemical-induced liver damage. Drug-induced hepatic injury is the most frequent reason used for the withdrawal from the market of an approved drug, and it also accounts for more than 50 per cent of the cases of acute liver failure in the United States today. More than 75 per cent of cases of idiosyncratic (a dose of a drug induces an unexpected allergic reaction) drug reactions results in liver transplantation or death. Drug Metabolism In Liver: - Biotransformation is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems, Liver is central to the metabolism of virtually every foreign substance. Most drugs and xenobiotics are lipophilic (lipid soluble) , enabling them to cross the membranes of intestinal cells. (the more a substance is lipophilic more it is diffused)  Drugs are rendered more hydrophilic by biochemical processes in the hepatocyte, yielding water-soluble p

Drug Induced Immune Mediated Hepatotoxicity / Liver Damage -

Role of the innate immune system NAPQI induce liver damage trigger activation and inflammatory responses of the innate immune system causing the production of inflammatory mediators, including cytokines, chemokines, and reactive oxygen and nitrogen species that contribute to the progression of liver injury. Some of these mediators, such as IFN-, Fas, or Fas ligand, are directly involved in causing liver damage. Mutant mice lacking these factors are resistant to APAP hepatotoxicity.APAP hepatotoxicity leads to the activation of KC.KC activation results in the release of pro-inflammatory mediators which are TNF( directly induce tissue damage), IL-12 and IL-18, activators of NK and NKT cells. KC may also play a protective role. They are a source of IL-10 and IL-6, important in counteracting inflammatory responses and stimulating liver regeneration. Role Of Adaptive Immune System Clinical Signs: Following are the clinical characteristics which show involvement of the adaptive immune sy

Drugs Causing Hapatotoxicity or liver damage

1. Analgesics Aspirin has recently been recognized as potentially hepatotoxic. Almost all reported cases have occurred in children and young adults with connective tissue disorders such as Still's disease, rheumatoid arthritis and systemic lupus erythematosus, and females have been affected more often than males. Aspirin has been involved in the great majority of cases. About 50 % of patients with juvenile rheumatoid arthritis have evidence of some degree of liver injury as shown by elevation of plasma aminotransferases during conventional high-dosage aspirin therapy. Another drug in this category includes gabapentin which shows hepatotoxicity as one of its side effects. 2. Anti-Tuberculosis Drugs Hepatotoxicity is one of the most important adverse drug reactions associated with anti-tuberculosis drugs that may limit their use. Previous studies showed transient elevations of serum hepatocellular enzymes (e.g. alanine aminotransferase and aspartate aminotransferase) in approxima

What is Liver Injury - Difference between Drug Induce Liver damage and pathological Liver damage -

Liver Injury:  Liver injury is defined as rising in either (a) ALT level more than three times of upper limit of normal (ULN) (b) ALP level more than twice ULN (upper limit normal) (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular (predominantly initial Alanine transferase elevation)  cholestatic (initial alkaline phosphatase rise) types. Specific histo-pathological patterns of liver injury from drug-induced damage are discussed below. Zonal Necrosis : This is the most common type of drug-induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule. It may manifest as a very high level of ALT and severe disturbance of liver function leading to acute liver failure. Drugs include: Paracetamol, carbon tetrachloride Hepatitis: In this pattern hepatocellular necrosis is associated with infiltration of inflammatory cells. There can

Strep Sore Throat-Causes-Signs-Symptoms-Treatment-Complications