Non-Alcoholic Fatty Liver Disease or
Non-alcoholic steatohepatitis
From Wikipedia, the free encyclopedia
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Classification and external resources
ICD-10
K76.0
ICD-9
571.8
DiseasesDB
29786
eMedicine
med/775
Non-alcoholic fatty liver disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome, and may respond to treatments originally developed for other insulin resistant states (e.g. diabetes mellitus type 2), such as weight loss, metformin and thiazolidinediones.[1] Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD, which is regarded as a major cause of cirrhosis of the liver of unknown cause.[2]
NASH was first described in 1980 in a series of patients of the Mayo Clinic.[3] Its relevance and high prevalence were recognized mainly in the 1990s. Some feel that NASH is a diagnosis of exclusion, and that many cases may be in fact be due to other causes.[4]
Contents[hide]
1 Signs and symptoms
1.1 Symptoms and associations
1.2 Secondary causes
2 Diagnosis
3 Pathophysiology
4 Treatment
5 See also
6 References
7 External links
//
[edit] Signs and symptoms
[edit] Symptoms and associations
Most patients with NAFLD have no or few symptoms. Infrequently, patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice may, rarely, be noticed. More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood tests. By definition, alcohol consumption of over 20 g/day (about 25ml/day) excludes the condition.[1]
NAFLD is associated with insulin resistance and the metabolic syndrome (obesity, combined hyperlipidemia, diabetes mellitus (type II) and high blood pressure).[2][1]
[edit] Secondary causes
NAFLD can also be caused by the following medications (termed secondary NAFLD):[citation needed]
Amiodarone
Antiviral drugs (nucleoside analogues)
Aspirin / NSAIDs
Corticosteroids
Methotrexate
Nifedipine
Perhexiline
Tamoxifen
Tetracycline
Valproic acid
[edit] Diagnosis
Disturbed liver enzymes are common, and liver ultrasound may show steatosis; it may also be used to exclude gallstone problems (cholelithiasis). A biopsy (tissue examination) of the liver is the only test which is widely accepted as definitively distinguishing NASH from other forms of liver disease, and can be used to assess the severity of the inflammation and resultant fibrosis.[1]
Other tests are often carried out. Relevant blood tests include erythrocyte sedimentation rate, glucose, albumin, and renal function etc. As the liver is important in coagulation, some coagulation studies are often carried out, especially the INR (international normalized ratio). Blood tests (serology) are usually carried out to rule out viral hepatitis (hepatitis A, B, C, EBV, CMV and herpes viruses), rubella, and autoimmune causes. Hypothyroidism is more prevalent in NASH patients, which would be detected by determining the TSH.[5]
Some suggest that in overweight patients whose blood tests do not improve on losing weight and exercising, a further search of underlying causes of fatty liver must be sought, as well as those with fatty liver who are very young or not overweight or insulin resistant, those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those who present with moderate to advanced fibrosis or cirrhosis.[4]
[edit] Pathophysiology
NAFLD is considered to cover a spectrum of disease activity. This spectrum begins as fatty accumulation in the liver (hepatic steatosis). A liver can remain fatty without disturbing liver function, but by varying mechanisms and possible insults to the liver may also progress to outright inflammation of the liver. When inflammation occurs in this setting, the condition is then called NASH. Over time up to 20 percent of patients with NASH may develop cirrhosis.[citation needed] Cigarette smoking is not associated with an increased risk of developing NASH.
The exact cause of NAFLD is still unknown. However, both obesity and insulin resistance probably play a strong role in the disease process. The exact reasons and mechanisms by which the disease progresses from one stage to the next are the subject of much research and debate.
One debated mechanism proposes a "second hit", or further injury, enough to cause change that leads from hepatic steatosis to hepatic inflammation. Oxidative stress, hormonal imbalances and mitochondrial abnormalities are potential causes for this "second hit" phenomenon.[1]
[edit] Treatment
Trials to optimise treatment of NASH are being conducted (2007), and no treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake.[1]
A large number of treatments for NAFLD have been studied. While many appear to improve biochemical markers such as alanine transaminase levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints:[1].
Treatment of nutrition and excessive body weight:
Nutritional counseling: Diet changes have shown significant histological improvement.[6]
Weight loss: gradual weight loss may improve the process in obese patients; rapid loss may worsen NAFLD. The bad effect of rapid weight loss is controversial: the results of a meta-analysis showed that the risk of progression is very low.[1]
A recent meta-analysis presented at the Annual Meeting of American Association for Study of Liver Diseases(AASLD) reported that weight-loss surgery leads to improvement and or resolution of NASH in around 80 % of patients.[2]
Insulin sensitisers (metformin[7] and thiazolidinediones[8]) have shown efficacy in some studies.
Antioxidants and ursodeoxycholic acid, as well as lipid-lowering drugs, have little benefit.[citation needed]
In a study using the NHANES III dataset, it has been shown that mild alcohol consumption (one glass of wine a day) reduces the risk of NAFLD by half.[9]
[edit] See also
Fatty liver includes both non-alcoholic and alcoholic liver disease
Alcoholic liver disease
[edit] References
^ a b c d e f g Adams LA, Angulo P (2006). "Treatment of non-alcoholic fatty liver disease". Postgrad Med J 82: 315–22. doi:10.1136/pgmj.2005.042200. PMID 16679470. http://pmj.bmj.com/cgi/content/full/82/967/315.
^ a b Clark JM, Diehl AM (2003). "Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis". JAMA 289: 3000–4. doi:10.1001/jama.289.22.3000. PMID 12799409.
^ Ludwig J, Viggiano TR, McGill DB, Oh BJ (1980). "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease". Mayo Clin Proc 55. PMID 7382552.
^ a b Cassiman D, Jaeken J (2008). "NASH may be trash". Gut 57 (2): 141–4. doi:10.1136/gut.2007.123240. PMID 18192446.
^ Liangpunsakul S, Chalasani N (2003). "Is hypothyroidism a risk factor for non-alcoholic steatohepatitis?". J Clin Gastroenterol 37: 340–3. doi:10.1097/00004836-200310000-00014. PMID 14506393.
^ Huang MA, Greenson JK, Chao C, et al (2005). "One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study". Am. J. Gastroenterol. 100 (5): 1072–81. doi:10.1111/j.1572-0241.2005.41334.x. PMID 15842581.
^ Bugianesi E, Gentilcore E, Manini R, et al (2005). "A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease". Am. J. Gastroenterol. 100 (5): 1082–90. doi:10.1111/j.1572-0241.2005.41583.x. PMID 15842582.
^ Belfort R, Harrison SA, Brown K, et al (2006). "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis". N. Engl. J. Med. 355 (22): 2297–307. doi:10.1056/NEJMoa060326. PMID 17135584.
^ Dunn W, Xu R, Schwimmer JB (February 2008). "Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease". Hepatology 47 (6): 1947–1954. doi:10.1002/hep.22292. PMID 18454505.
[edit] External links
Medscape article on NASH.
MEDICINENET article on Steatosis.
NIH page on Nonalcoholic Steatohepatitis
[hide]
v • d • eDigestive system · Digestive disease · Gastroenterology (primarily K20-K93, 530-579)
Upper GI tract
Esophagus
Esophagitis (Candidal) · rupture (Boerhaave syndrome, Mallory-Weiss syndrome) · UES (Zenker's diverticulum) · LES (Barrett's esophagus) · Esophageal motility disorder (Nutcracker esophagus, Achalasia, Diffuse esophageal spasm, GERD) · Esophageal stricture · Megaesophagus
Stomach
Gastritis (Atrophic, Ménétrier's disease, Gastroenteritis) · Peptic (gastric) ulcer (Cushing ulcer, Dieulafoy's lesion) · Dyspepsia · Pyloric stenosis · Achlorhydria · Gastroparesis · Gastroptosis · Portal hypertensive gastropathy · Gastric antral vascular ectasia · Gastric dumping syndrome · Gastric volvulus
Intestinal/enteropathy
Small intestine/(duodenum/jejunum/ileum)
Enteritis (Duodenitis, Jejunitis, Ileitis) — Peptic (duodenal) ulcer (Curling's ulcer) — Malabsorption: Coeliac · Tropical sprue · Blind loop syndrome · Whipple's · Short bowel syndrome · Steatorrhea · Milroy disease
Large intestine(appendix/colon)
Appendicitis · Colitis (Pseudomembranous, Ulcerative, Ischemic, Microscopic, Collagenous, Lymphocytic) · Functional colonic disease (IBS, Intestinal pseudoobstruction/Ogilvie syndrome) — Megacolon/Toxic megacolon · Diverticulitis/Diverticulosis
Large and/or small
Enterocolitis (Necrotizing) · IBD (Crohn's disease) — vascular: Abdominal angina · Mesenteric ischemia · Angiodysplasia — Bowel obstruction: Ileus · Intussusception · Volvulus · Fecal impaction — Constipation · Diarrhea (Infectious)
Rectum
Proctitis (Radiation proctitis) · Proctalgia fugax · Rectal prolapse
Anus
Anal fissure/Anal fistula · Anal abscess · Anal dysplasia · Pruritus ani
Accessory
Liver
Hepatitis (Viral hepatitis, Autoimmune hepatitis, Alcoholic hepatitis) · Cirrhosis (PBC) · Fatty liver (NASH) · vascular (Hepatic veno-occlusive disease, Portal hypertension, Nutmeg liver) · Alcoholic liver disease · Liver failure (Hepatic encephalopathy, Acute liver failure) · Liver abscess (Pyogenic, Amoebic) · Hepatorenal syndrome · Peliosis hepatis
Gallbladder
Cholecystitis · Gallstones/Cholecystolithiasis · Cholesterolosis · Rokitansky-Aschoff sinuses · Postcholecystectomy syndrome
Bile duct/other biliary tree
Cholangitis (PSC, Secondary sclerosing cholangitis, Ascending) · Cholestasis/Mirizzi's syndrome · Biliary fistula · Haemobilia · Gallstones/Cholelithiasiscommon bile duct (Choledocholithiasis, Biliary dyskinesia)
Pancreatic
Pancreatitis (Acute, Chronic, Hereditary) · Pancreatic pseudocyst · Exocrine pancreatic insufficiency · Pancreatic fistula
Hernia
Diaphragmatic: Congenital diaphragmatic · Hiatus — Abdominal hernia: Inguinal (Indirect, Direct) · Umbilical · Incisional · Femoral — Obturator hernia · Spigelian hernia · Internal hernia
Peritoneal
Peritonitis (Spontaneous bacterial peritonitis) · Hemoperitoneum · Pneumoperitoneum
GI bleeding/BIS
Upper (Hematemesis, Melena) · Lower (Hematochezia)
See also: congenital and neoplasia
Retrieved from "http://en.wikipedia.org/wiki/Non-alcoholic_fatty_liver_disease"
Categories: Gastroenterology Hepatitis
Hidden categories: All articles with unsourced statements Articles with unsourced statements since February 2007 Articles with unsourced statements since March 2008 Articles with unsourced statements since May 2008
From Wikipedia, the free encyclopedia
Non-alcoholic steatohepatitis
Classification and external resources
ICD-10
K76.0
ICD-9
571.8
DiseasesDB
29786
eMedicine
med/775
Non-alcoholic fatty liver disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome, and may respond to treatments originally developed for other insulin resistant states (e.g. diabetes mellitus type 2), such as weight loss, metformin and thiazolidinediones.[1] Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD, which is regarded as a major cause of cirrhosis of the liver of unknown cause.[2]
NASH was first described in 1980 in a series of patients of the Mayo Clinic.[3] Its relevance and high prevalence were recognized mainly in the 1990s. Some feel that NASH is a diagnosis of exclusion, and that many cases may be in fact be due to other causes.[4]
Contents[hide]
1 Signs and symptoms
1.1 Symptoms and associations
1.2 Secondary causes
2 Diagnosis
3 Pathophysiology
4 Treatment
5 See also
6 References
7 External links
//
[edit] Signs and symptoms
[edit] Symptoms and associations
Most patients with NAFLD have no or few symptoms. Infrequently, patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice may, rarely, be noticed. More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood tests. By definition, alcohol consumption of over 20 g/day (about 25ml/day) excludes the condition.[1]
NAFLD is associated with insulin resistance and the metabolic syndrome (obesity, combined hyperlipidemia, diabetes mellitus (type II) and high blood pressure).[2][1]
[edit] Secondary causes
NAFLD can also be caused by the following medications (termed secondary NAFLD):[citation needed]
Amiodarone
Antiviral drugs (nucleoside analogues)
Aspirin / NSAIDs
Corticosteroids
Methotrexate
Nifedipine
Perhexiline
Tamoxifen
Tetracycline
Valproic acid
[edit] Diagnosis
Disturbed liver enzymes are common, and liver ultrasound may show steatosis; it may also be used to exclude gallstone problems (cholelithiasis). A biopsy (tissue examination) of the liver is the only test which is widely accepted as definitively distinguishing NASH from other forms of liver disease, and can be used to assess the severity of the inflammation and resultant fibrosis.[1]
Other tests are often carried out. Relevant blood tests include erythrocyte sedimentation rate, glucose, albumin, and renal function etc. As the liver is important in coagulation, some coagulation studies are often carried out, especially the INR (international normalized ratio). Blood tests (serology) are usually carried out to rule out viral hepatitis (hepatitis A, B, C, EBV, CMV and herpes viruses), rubella, and autoimmune causes. Hypothyroidism is more prevalent in NASH patients, which would be detected by determining the TSH.[5]
Some suggest that in overweight patients whose blood tests do not improve on losing weight and exercising, a further search of underlying causes of fatty liver must be sought, as well as those with fatty liver who are very young or not overweight or insulin resistant, those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those who present with moderate to advanced fibrosis or cirrhosis.[4]
[edit] Pathophysiology
NAFLD is considered to cover a spectrum of disease activity. This spectrum begins as fatty accumulation in the liver (hepatic steatosis). A liver can remain fatty without disturbing liver function, but by varying mechanisms and possible insults to the liver may also progress to outright inflammation of the liver. When inflammation occurs in this setting, the condition is then called NASH. Over time up to 20 percent of patients with NASH may develop cirrhosis.[citation needed] Cigarette smoking is not associated with an increased risk of developing NASH.
The exact cause of NAFLD is still unknown. However, both obesity and insulin resistance probably play a strong role in the disease process. The exact reasons and mechanisms by which the disease progresses from one stage to the next are the subject of much research and debate.
One debated mechanism proposes a "second hit", or further injury, enough to cause change that leads from hepatic steatosis to hepatic inflammation. Oxidative stress, hormonal imbalances and mitochondrial abnormalities are potential causes for this "second hit" phenomenon.[1]
[edit] Treatment
Trials to optimise treatment of NASH are being conducted (2007), and no treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake.[1]
A large number of treatments for NAFLD have been studied. While many appear to improve biochemical markers such as alanine transaminase levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints:[1].
Treatment of nutrition and excessive body weight:
Nutritional counseling: Diet changes have shown significant histological improvement.[6]
Weight loss: gradual weight loss may improve the process in obese patients; rapid loss may worsen NAFLD. The bad effect of rapid weight loss is controversial: the results of a meta-analysis showed that the risk of progression is very low.[1]
A recent meta-analysis presented at the Annual Meeting of American Association for Study of Liver Diseases(AASLD) reported that weight-loss surgery leads to improvement and or resolution of NASH in around 80 % of patients.[2]
Insulin sensitisers (metformin[7] and thiazolidinediones[8]) have shown efficacy in some studies.
Antioxidants and ursodeoxycholic acid, as well as lipid-lowering drugs, have little benefit.[citation needed]
In a study using the NHANES III dataset, it has been shown that mild alcohol consumption (one glass of wine a day) reduces the risk of NAFLD by half.[9]
[edit] See also
Fatty liver includes both non-alcoholic and alcoholic liver disease
Alcoholic liver disease
[edit] References
^ a b c d e f g Adams LA, Angulo P (2006). "Treatment of non-alcoholic fatty liver disease". Postgrad Med J 82: 315–22. doi:10.1136/pgmj.2005.042200. PMID 16679470. http://pmj.bmj.com/cgi/content/full/82/967/315.
^ a b Clark JM, Diehl AM (2003). "Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis". JAMA 289: 3000–4. doi:10.1001/jama.289.22.3000. PMID 12799409.
^ Ludwig J, Viggiano TR, McGill DB, Oh BJ (1980). "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease". Mayo Clin Proc 55. PMID 7382552.
^ a b Cassiman D, Jaeken J (2008). "NASH may be trash". Gut 57 (2): 141–4. doi:10.1136/gut.2007.123240. PMID 18192446.
^ Liangpunsakul S, Chalasani N (2003). "Is hypothyroidism a risk factor for non-alcoholic steatohepatitis?". J Clin Gastroenterol 37: 340–3. doi:10.1097/00004836-200310000-00014. PMID 14506393.
^ Huang MA, Greenson JK, Chao C, et al (2005). "One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study". Am. J. Gastroenterol. 100 (5): 1072–81. doi:10.1111/j.1572-0241.2005.41334.x. PMID 15842581.
^ Bugianesi E, Gentilcore E, Manini R, et al (2005). "A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease". Am. J. Gastroenterol. 100 (5): 1082–90. doi:10.1111/j.1572-0241.2005.41583.x. PMID 15842582.
^ Belfort R, Harrison SA, Brown K, et al (2006). "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis". N. Engl. J. Med. 355 (22): 2297–307. doi:10.1056/NEJMoa060326. PMID 17135584.
^ Dunn W, Xu R, Schwimmer JB (February 2008). "Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease". Hepatology 47 (6): 1947–1954. doi:10.1002/hep.22292. PMID 18454505.
[edit] External links
Medscape article on NASH.
MEDICINENET article on Steatosis.
NIH page on Nonalcoholic Steatohepatitis
[hide]
v • d • eDigestive system · Digestive disease · Gastroenterology (primarily K20-K93, 530-579)
Upper GI tract
Esophagus
Esophagitis (Candidal) · rupture (Boerhaave syndrome, Mallory-Weiss syndrome) · UES (Zenker's diverticulum) · LES (Barrett's esophagus) · Esophageal motility disorder (Nutcracker esophagus, Achalasia, Diffuse esophageal spasm, GERD) · Esophageal stricture · Megaesophagus
Stomach
Gastritis (Atrophic, Ménétrier's disease, Gastroenteritis) · Peptic (gastric) ulcer (Cushing ulcer, Dieulafoy's lesion) · Dyspepsia · Pyloric stenosis · Achlorhydria · Gastroparesis · Gastroptosis · Portal hypertensive gastropathy · Gastric antral vascular ectasia · Gastric dumping syndrome · Gastric volvulus
Intestinal/enteropathy
Small intestine/(duodenum/jejunum/ileum)
Enteritis (Duodenitis, Jejunitis, Ileitis) — Peptic (duodenal) ulcer (Curling's ulcer) — Malabsorption: Coeliac · Tropical sprue · Blind loop syndrome · Whipple's · Short bowel syndrome · Steatorrhea · Milroy disease
Large intestine(appendix/colon)
Appendicitis · Colitis (Pseudomembranous, Ulcerative, Ischemic, Microscopic, Collagenous, Lymphocytic) · Functional colonic disease (IBS, Intestinal pseudoobstruction/Ogilvie syndrome) — Megacolon/Toxic megacolon · Diverticulitis/Diverticulosis
Large and/or small
Enterocolitis (Necrotizing) · IBD (Crohn's disease) — vascular: Abdominal angina · Mesenteric ischemia · Angiodysplasia — Bowel obstruction: Ileus · Intussusception · Volvulus · Fecal impaction — Constipation · Diarrhea (Infectious)
Rectum
Proctitis (Radiation proctitis) · Proctalgia fugax · Rectal prolapse
Anus
Anal fissure/Anal fistula · Anal abscess · Anal dysplasia · Pruritus ani
Accessory
Liver
Hepatitis (Viral hepatitis, Autoimmune hepatitis, Alcoholic hepatitis) · Cirrhosis (PBC) · Fatty liver (NASH) · vascular (Hepatic veno-occlusive disease, Portal hypertension, Nutmeg liver) · Alcoholic liver disease · Liver failure (Hepatic encephalopathy, Acute liver failure) · Liver abscess (Pyogenic, Amoebic) · Hepatorenal syndrome · Peliosis hepatis
Gallbladder
Cholecystitis · Gallstones/Cholecystolithiasis · Cholesterolosis · Rokitansky-Aschoff sinuses · Postcholecystectomy syndrome
Bile duct/other biliary tree
Cholangitis (PSC, Secondary sclerosing cholangitis, Ascending) · Cholestasis/Mirizzi's syndrome · Biliary fistula · Haemobilia · Gallstones/Cholelithiasiscommon bile duct (Choledocholithiasis, Biliary dyskinesia)
Pancreatic
Pancreatitis (Acute, Chronic, Hereditary) · Pancreatic pseudocyst · Exocrine pancreatic insufficiency · Pancreatic fistula
Hernia
Diaphragmatic: Congenital diaphragmatic · Hiatus — Abdominal hernia: Inguinal (Indirect, Direct) · Umbilical · Incisional · Femoral — Obturator hernia · Spigelian hernia · Internal hernia
Peritoneal
Peritonitis (Spontaneous bacterial peritonitis) · Hemoperitoneum · Pneumoperitoneum
GI bleeding/BIS
Upper (Hematemesis, Melena) · Lower (Hematochezia)
See also: congenital and neoplasia
Retrieved from "http://en.wikipedia.org/wiki/Non-alcoholic_fatty_liver_disease"
Categories: Gastroenterology Hepatitis
Hidden categories: All articles with unsourced statements Articles with unsourced statements since February 2007 Articles with unsourced statements since March 2008 Articles with unsourced statements since May 2008
Monday, May 04, 2009
Wednesday, November 12, 2008
Liver
Liver
From Wikipedia, the free encyclopedia
Anterior view of the position of the liver (red) in the human abdomen.
Latin
jecur
Gray's
subject #250 1188
Vein
hepatic vein, hepatic portal vein
Nerve
celiac ganglia, vagus[1]
Precursor
foregut
MeSH
Liver
The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for Digestion. The liver is necessary for survival; a human can only last up to 24 hours without liver function.
The liver plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, and detoxification. The liver is also the largest gland in the human body. It lies below the diaphragm in the thoracic region of the abdomen. It produces bile, an alkaline compound which aids in digestion, via the emulsification of lipids (fats). It also performs and regulates a wide variety of high-volume biochemical reactions requiring very specialized tissues.[2]
Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hēpar (ήπαρ).[3]
Anatomy
The adult human liver normally weighs between 1.4 - 1.6 kilograms (3.1 - 3.5 pounds),[4] and it is a soft, pinkish-brown, triangular organ. Averaging about the size of an American football in adults, it is both the largest internal organ and the largest gland in the human body.
It is located on the right side of the upper abdomen below the diaphragm anatomy. The liver lies to the right of the stomach and overlies the Gallbladder .
Flow of blood
The splenic vein joins the inferior mesenteric vein, which then together join the superior mesenteric vein to form the hepatic portal vein, bringing venous blood from the spleen, The Pancreas, Stomach, small intestine, and large intestine, so that the liver can process the nutrients and by-products of food digestion.
The hepatic veins of the blood can be from other branches such as the superior mesenteric artery.
Both the portal venules & the hepatic arterioles enter approximately one million identical lobules acini, likened to and changes in the size of chylomicrons lipoproteins of dietary origin brought about by the quantity & types of food fats.
Approximately 60% to 80% of the blood flow to the liver is from the portal venous system, and 1/5th of blood flow is from the hepatic artery.
Flow of bile
The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts.
These eventually drain into the right and left hepatic ducts, which in turn merge to form the common hepatic duct. The cystic duct (from the gallbladder) joins with the common hepatic duct to form the common bile duct.
Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the duodenum together at the Ampulla of Vater.
The branchings of the bile ducts resemble those of a tree, and indeed the term "Biliary Tree", is commonly used in this setting.
The Biliary Tree.
Regeneration
The liver is among the few internal human organs capable of natural regeneration of lost tissue; as little as 25% of a liver can regenerate into a whole liver.
This is predominantly due to the hepatocytes re-entering the cell cycle (i.e. the hepatocytes go from the quiescent G0 phase to the G1 phase and undergo mitosis). There is also some evidence of bipotential stem cells, called ovalocyte (o´və-lo-sīt), which exist in the Canals of Hering. These cells can differentiate into either hepatocytes or cholangiocytes (cells that line the bile ducts).
Traditional (Surface) anatomy
Peritoneal ligaments
Apart from a patch where it connects to the diaphragm, the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments.
These "ligaments" are in no way related to the true anatomic ligaments in joints, and have essentially no functional importance, but they are easily recognizable surface landmarks.
Lobes
Traditional gross anatomy divided the liver into four lobes based on surface features. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.
If the liver flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe.
From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.
Each of the lobes is made up of lobules, a vein goes from the centre of each lobule which then joins to the hepatic vein to carry blood out from the liver.
On the surface of the lobules there are ducts, veins and arteries that carry fluids to and from them.
Modern (Functional) anatomy
The central area where the common bile duct, hepatic portal vein, and hepatic artery enter is the hilum or "porta hepatis". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes.
The liver performs over 500 jobs, and produces over 1,000 essential enzymes.
The functional lobes are separated by a plane joining the gallbladder fossa to the inferior vena cava. This separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by the left hepatic vein. The fissure for the ligamentum teres (the ligamentum teres becomes the falciform ligament) also separates the medial and lateral segments. The medial segment is what used to be called the quadrate lobe. In the widely used Couinaud or "French" system, the functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein. The caudate lobe is a separate structure which receives blood flow from both the right- and left-sided vascular branches.[5][6] The subsegments corresponding to the anatomical lobes are as follows:
Segment*
Couinaud segments
Caudate...1
Lateral.....2, 3
Medial.....4a, 4b
Right.......5, 6, 7, 8
or lobe in the Caudate's case.
Each number in the list corresponds to one in the table.
- Caudate
- Superior subsegment of the lateral segment
- Inferior subsegment of the lateral segment
- a
- b
- Inferior subsegment of the medial segment
- Inferior subsegment of the anterior segment
- Superior subsegment of the posterior segment
- Superior subsegment of the anterior segment
Physiology
The various functions of the liver are carried out by the liver cells or hepatocytes.
The liver produces and excretes bile (a greenish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
- The liver performs several roles in carbohydrate metabolism:
- Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or
glycerol) - Glycogenolysis (the breakdown of glycogen into glucose) (muscle
tissues can also do this) - Glycogenesis (the formation of glycogen from
glucose) - The breakdown of insulin and other hormones
- The liver is responsible for the mainstay of protein metabolism. For instance, the liver can convert lactic acid to alanine.
- The liver also performs several roles in lipid (fat) metabolism:
- Cholesterol synthesis
- Lipogenesis, the production
of triglycerides (fats). - The liver produces coagulation factors I (fibrinogen), II
(prothrombin), V, VII, IX, X and XI, as well as protein C, protein S
and antithrombin. - The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment (bilirubin and biliverdin).
- The liver breaks down toxic substances and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor.
- The liver converts ammonia to urea.
- The liver stores a multitude of substances, including glucose (in the form of glycogen), vitamin A (1-2 years' supply), vitamin D (1-4 months' supply), vitamin B12, iron, and copper.
- In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task.
- The liver is responsible for immunological effects- the reticuloendothelial system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the portal system.
- The liver produces albumin, the major osmolar component of blood serum.
Currently, there is no artificial organ or device capable of emulating all the functions of the liver. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.
Diseases of the liver
Main article: Liver disease
Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, and Langerhans cell histiocytosis to name but a few.
Liver transplantation
Main article: Liver transplantation
Human liver transplant was first performed by Thomas Starzl in USA and Roy Calne in Cambridge, England in 1963 and 1965 respectively.
Liver transplantation is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for fulminate hepatic failure, in which liver failure occurs over days to weeks.
Liver allografts for transplant usually come from non-living donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couperin segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.
More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial as it entails performing a much larger operation on the donor, and indeed there have been at least 2 donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found.[7] The risk of postoperative complications (and death) is far greater in right sided hepatectomy than left sided operations.
With the recent advances of non-invasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operation.
Development
Fetal blood supply
In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus, and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing placental blood to bypass the liver.
In the fetus, the liver develops throughout normal gestation, and does not perform the normal filtration of the infant liver. The liver does not perform digestive processes because the fetus does not consume meals directly, but receives nourishment from the mother via the placenta. The fetal liver releases some blood stem cells that migrate to the fetal thymus, so initially the lymphocyte, called T-cells, are created from fetal liver stem cells. Once the fetus is delivered, the formation of blood stem cells in infants shifts to the red bone marrow.
After birth, the umbilical vein and ductus venosus are completely obliterated two to five days postpartum; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum. In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.
Cultural allusions
In Greek mythology, Prometheus was punished by the gods for revealing fire to humans, by being chained to a rock where a vulture (or an eagle) would peck out his liver, which would regenerate overnight. (The liver is the only human internal organ that actually can regenerate itself to a significant extent.)
Many ancient peoples of the Near East and Mediterranean areas practised a type of divination called haruspicy, whereby they tried to obtain information from examining the livers of sheep and other animals.
The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.
In Arabic, Persian and Urdu languages, the liver is used in figurative speech to refer to courage and strong feelings, or "their best," e.g. "This Mecca has thrown to you the pieces of its liver!" [10]. The term jan e jigar literally "the strength (power) of my liver" is a term of endearment in Urdu.
In Persian Slang, Liver (Persian: جگر)Is Used as An Adjective for Any Object Which Is So Desirable (esp Women)
The legend of Liver-Eating Johnson says that he would cut out and eat the liver of each man killed after dinner.
In the motion picture The Message, Hind bint Utbah is implied or portrayed eating the liver of Hamza ibn ‘Abd al-Muttalib during the Battle of Uhud.
Inuit will not eat the liver of polar bears (a polar bear's liver contains so much Vitamin A as to be poisonous to humans), or seals [11]
See also
Look up liver in Wiktionary, the free dictionary.
Artificial liver
Bile
Bile canaliculus
Hepatocyte
Liver function tests
Further reading
The following are standard medical textbooks:
Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, eds. Schiff's diseases of the liver, 9th ed. Philadelphia : Lippincott, Williams & Wilkins, 2003. ISBN 0-7817-3007-4
Sheila Sherlock, James Dooley. Diseases of the liver and biliary system, 11th ed. Oxford, UK ; Malden, MA : Blackwell Science. 2002. ISBN 0-632-05582-0
David Zakim, Thomas D. Boyer. eds. Hepatology: a textbook of liver disease, 4th ed. Philadelphia: Saunders. 2003. ISBN 0-7216-9051-3
These are for the lay reader or patient:
Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0-7434-0585-4
Melissa Palmer. Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know, Avery Publishing Group; Revised edition May 24, 2004, ISBN 1-58333-188-3. her webpage.
Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0-7373-0090-6. his Columbia University web site, "Diseases of the liver"
References
^ Physiology at MCG 6/6ch2/s6ch2_30
^ Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. OCLC 32308337.
^ The Greek word "ήπαρ" was derived from hēpaomai (ηπάομαι): to mend, to repair, hence hēpar actually means "repairable", indicating that this organ can regenerate itself spontaneously in the case of lesion.
^ Robbins and Cotran Pathologic Basis of Disease, 7th Edition, p. 878
^ Three-dimensional Anatomy of the Couinaud Liver Segments - University of Iowa
^ Limitations and Pitfalls of Couinaud`s Segmentation of the Liver in Transaxial Imaging - Prof. Dr. Holger Strunk
^ Bramstedt K (2006). "Living liver donor mortality: where do we stand?". Am J Gastrointestinal 101 (4): 755–9. doi:10.1111/j.1572-0241.2006.00421.x. PMID 16494593.
^ A. Aggrawal, Death by Vitamin A
^ Myhre et al., "Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations", Am. J. Clinical Nutrition, 78, 1152 (2003)
^ THE GREAT BATTLE OF BADAR (Yaum-e-Furqan)
^ Man's best friend? - Student BMJ
Diseases of the liver
Main article: Liver disease
Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, and Langerhans cell histiocytosis to name but a few.
Liver transplantation
Main article: Liver transplantation
Human liver transplant was first performed by Thomas Starzl in USA and Roy Calne in Cambridge, England in 1963 and 1965 respectively.
Liver transplantation is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for fulminate hepatic failure, in which liver failure occurs over days to weeks.
Liver allografts for transplant usually come from non-living donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couperin segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.
More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial as it entails performing a much larger operation on the donor, and indeed there have been at least 2 donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found.[7] The risk of postoperative complications (and death) is far greater in right sided hepatectomy than left sided operations.
With the recent advances of non-invasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operation.
Development
Fetal blood supply
In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus, and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing placental blood to bypass the liver.
In the fetus, the liver develops throughout normal gestation, and does not perform the normal filtration of the infant liver. The liver does not perform digestive processes because the fetus does not consume meals directly, but receives nourishment from the mother via the placenta. The fetal liver releases some blood stem cells that migrate to the fetal thymus, so initially the lymphocyte, called T-cells, are created from fetal liver stem cells. Once the fetus is delivered, the formation of blood stem cells in infants shifts to the red bone marrow.
After birth, the umbilical vein and ductus venosus are completely obliterated two to five days postpartum; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum. In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.
Cultural allusions
In Greek mythology, Prometheus was punished by the gods for revealing fire to humans, by being chained to a rock where a vulture (or an eagle) would peck out his liver, which would regenerate overnight. (The liver is the only human internal organ that actually can regenerate itself to a significant extent.)
Many ancient peoples of the Near East and Mediterranean areas practised a type of divination called haruspicy, whereby they tried to obtain information from examining the livers of sheep and other animals.
The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.
In Arabic, Persian and Urdu languages, the liver is used in figurative speech to refer to courage and strong feelings, or "their best," e.g. "This Mecca has thrown to you the pieces of its liver!" [10]. The term jan e jigar literally "the strength (power) of my liver" is a term of endearment in Urdu.
In Persian Slang, Liver (Persian: جگر)Is Used as An Adjective for Any Object Which Is So Desirable (esp Women)
The legend of Liver-Eating Johnson says that he would cut out and eat the liver of each man killed after dinner.
In the motion picture The Message, Hind bint Utbah is implied or portrayed eating the liver of Hamza ibn ‘Abd al-Muttalib during the Battle of Uhud.
Inuit will not eat the liver of polar bears (a polar bear's liver contains so much Vitamin A as to be poisonous to humans), or seals [11]
See also
Look up liver in Wiktionary, the free dictionary.
Artificial liver
Bile
Bile canaliculus
Hepatocyte
Liver function tests
Further reading
The following are standard medical textbooks:
Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, eds. Schiff's diseases of the liver, 9th ed. Philadelphia : Lippincott, Williams & Wilkins, 2003. ISBN 0-7817-3007-4
Sheila Sherlock, James Dooley. Diseases of the liver and biliary system, 11th ed. Oxford, UK ; Malden, MA : Blackwell Science. 2002. ISBN 0-632-05582-0
David Zakim, Thomas D. Boyer. eds. Hepatology: a textbook of liver disease, 4th ed. Philadelphia: Saunders. 2003. ISBN 0-7216-9051-3
These are for the lay reader or patient:
Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0-7434-0585-4
Melissa Palmer. Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know, Avery Publishing Group; Revised edition May 24, 2004, ISBN 1-58333-188-3. her webpage.
Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0-7373-0090-6. his Columbia University web site, "Diseases of the liver"
References
^ Physiology at MCG 6/6ch2/s6ch2_30
^ Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. OCLC 32308337.
^ The Greek word "ήπαρ" was derived from hēpaomai (ηπάομαι): to mend, to repair, hence hēpar actually means "repairable", indicating that this organ can regenerate itself spontaneously in the case of lesion.
^ Robbins and Cotran Pathologic Basis of Disease, 7th Edition, p. 878
^ Three-dimensional Anatomy of the Couinaud Liver Segments - University of Iowa
^ Limitations and Pitfalls of Couinaud`s Segmentation of the Liver in Transaxial Imaging - Prof. Dr. Holger Strunk
^ Bramstedt K (2006). "Living liver donor mortality: where do we stand?". Am J Gastrointestinal 101 (4): 755–9. doi:10.1111/j.1572-0241.2006.00421.x. PMID 16494593.
^ A. Aggrawal, Death by Vitamin A
^ Myhre et al., "Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations", Am. J. Clinical Nutrition, 78, 1152 (2003)
^ THE GREAT BATTLE OF BADAR (Yaum-e-Furqan)
^ Man's best friend? - Student BMJ
Saturday, October 14, 2006
Liver Diseases
.
The liver, the largest organ in the body, is essential in keeping the body functioning properly. It removes or neutralizes poisons from the blood, produces immune agents to control infection, and removes germs and bacteria from the blood. It makes proteins that regulate blood clotting and produces bile to help absorb fats and fat-soluble vitamins. You cannot live without a functioning liver.
In cirrhosis of the liver, scar tissue replaces normal, healthy tissue, blocking the flow of blood through the organ and preventing it from working as it should. Cirrhosis is the twelfth leading cause of death by disease, killing about 26,000 people each year. Also, the cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.
Diseases of the Liver
This resource is an alphabetical list of liver diseases and conditions with hypertext links to files at this site, or to other sites, that provide relevant information. It also has a links to:
Programs in Liver Diseases at Columbia-Presbyterian
Current Papers in Liver Disease
Books on Liver Disease
Other Liver-related Internet Resources
Click to Order Book
Diseases of the Liver is edited and produced by:
Howard J. Worman, M. D.
Division of Digestive and Liver Diseases
Departments of Medicine and of Anatomy and Cell Biology
College of Physicians & Surgeons
Columbia University
New York, NY 10032
Email: hjw14@columbia.edu
Last updated on January 8, 2003.
--------------------------------------------------------------------------------
Diseases of the Liver
- Alagille Syndrome
From Online Mendelian Inheritance in Man. - Alcoholic Liver Disease
From Howard J. Worman, M. D. - Alpha-1-antitrypsin Deficiency
Information from several sources. - Autoimmune Hepatitis
From Howard J. Worman, M. D. - Budd-Chiari Syndrome
From Howard J. Worman, M. D. - Biliary Atresia From the Children's Liver Association for Support Services.
- Byler Disease
From Online Mendelian Inheritance in Man. - Cancer of the Liver
From Howard J. Worman, M. D. - Caroli Disease
From Online Mendelian Inheritance in Man. - Cirrhosis
From Howard J. Worman, M. D. - Crigler-Najjar Syndrome
From Online Mendelian Inheritance in Man. - Dubin-Johnson Syndrome
From Online Mendelian Inheritance in Man. - Fatty Liver
From Howard J. Worman,M. D. - Galactosemia
From Online Mendelian Inheritance in Man. - Gilbert Syndrome
From Online Mendelian Inheritance in Man. - Glycogen Storage Disease I
From Online Mendelian Inheritance in Man. - Hemangioma
From Howard J. Worman, M. D. - Hemochromatosis
From Online Mendelian Inheritance in Man. - Hepatitis A
Information from several sources. - Hepatitis B
From Howard J. Worman, M. D. - Hepatitis C
From Howard J. Worman, M. D.
- Hepatitis D
From Howard J. Worman, M. D. - Hepatitis E
From the Center for Food Safety and Applied Nutrition of the Food and Drug Administration. - Hepatitis G
From Howard J. Worman, M. D. - Itching in Liver Disease
From Nora V. Bergasa, M. D. - Laboratory Tests in Liver Disease
From Howard J. Worman, M. D. - Liver Transplantation
From Dianne LaPointe Rudow, R. N., N. P. and Robert S. Brown, Jr., M. D., M. P. H. - Porphyria Cutanea Tardahttp:
From Online Mendelian Inheritance in Man. - Primary Biliary Cirrhosis
From Howard J. Worman, M. D. - Protoporphyria, Erythrohepatic
From Online Mendelian Inheritance in Man. - Rotor Syndrome
From Online Mendelian Inheritance in Man. - Sclerosing Cholangitis From Howard J. Worman, M. D.
- Wilson Disease
From Online Mendelian Inheritance in Man.
Current Papers in Liver Disease
Programs in Liver Diseases at Columbia-Presbyterian
Books on Liver Disease
Other Liver-Related Internet Resources
Order Dr. Worman's The Liver Disorders Sourcebook
Copyright, 1995-2002, Howard J. Worman, M. D. All rights reserved. Printing or other reproduction is prohibited without the written authorization of Howard J. Worman.
Diseases of the Liver/Howard J. Worman, M. D./hjw14@columbia.edu
To learn about another disease, click on Digestive diseases Library.
..
..
..
Causes
..
Cirrhosis has many causes. In the United States, chronic alcoholism and hepatitis C are the most common ones.
..
Alcoholic liver disease. To many people, cirrhosis of the liver is synonymous with chronic alcoholism, but in fact, alcoholism is only one of the causes. Alcoholic cirrhosis usually develops after more than a decade of heavy drinking. The amount of alcohol that can injure the liver varies greatly from person to person. In women, as few as two to three drinks per day have been linked with cirrhosis and in men, as few as three to four drinks per day. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.
..
Chronic hepatitis C. The hepatitis C virus ranks with alcohol as a major cause of chronic liver disease and cirrhosis in the United States. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.
..
Chronic hepatitis B and D. The hepatitis B virus is probably the most common cause of cirrhosis worldwide, but it is less common in the United States and the Western world. Hepatitis B, like hepatitis C, causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is another virus that infects the liver, but only in people who already have hepatitis B.
..
Autoimmune hepatitis. This disease appears to be caused by the immune system attacking the liver and causing inflammation, damage, and eventually scarring and cirrhosis.
Inherited diseases.
.....A. Alpha-1 antitrypsin deficiency;
.....B. hemochromatosis;
.....C. Wilson's disease;
.....D. galactosemia; and
.....E. glycogen storage diseases.
These are among the inherited diseases that interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.
..
Nonalcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
..
Blocked bile ducts. When the ducts that carry bile out of the liver are blocked, bile backs up and damages liver tissue. In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured. In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred. Secondary biliary cirrhosis can happen after gallbladder surgery if the ducts are inadvertently tied off or injured.
..
Drugs, toxins, and infections. Severe reactions to prescription drugs, prolonged exposure to environmental toxins, the parasitic infection schistosomiasis, and repeated bouts of heart failure with liver congestion can all lead to cirrhosis.
..
..
..
Cirrhosis has many causes. In the United States, chronic alcoholism and hepatitis C are the most common ones.
..
Alcoholic liver disease. To many people, cirrhosis of the liver is synonymous with chronic alcoholism, but in fact, alcoholism is only one of the causes. Alcoholic cirrhosis usually develops after more than a decade of heavy drinking. The amount of alcohol that can injure the liver varies greatly from person to person. In women, as few as two to three drinks per day have been linked with cirrhosis and in men, as few as three to four drinks per day. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.
..
Chronic hepatitis C. The hepatitis C virus ranks with alcohol as a major cause of chronic liver disease and cirrhosis in the United States. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.
..
Chronic hepatitis B and D. The hepatitis B virus is probably the most common cause of cirrhosis worldwide, but it is less common in the United States and the Western world. Hepatitis B, like hepatitis C, causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is another virus that infects the liver, but only in people who already have hepatitis B.
..
Autoimmune hepatitis. This disease appears to be caused by the immune system attacking the liver and causing inflammation, damage, and eventually scarring and cirrhosis.
Inherited diseases.
.....A. Alpha-1 antitrypsin deficiency;
.....B. hemochromatosis;
.....C. Wilson's disease;
.....D. galactosemia; and
.....E. glycogen storage diseases.
These are among the inherited diseases that interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.
..
Nonalcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
..
Blocked bile ducts. When the ducts that carry bile out of the liver are blocked, bile backs up and damages liver tissue. In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured. In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred. Secondary biliary cirrhosis can happen after gallbladder surgery if the ducts are inadvertently tied off or injured.
..
Drugs, toxins, and infections. Severe reactions to prescription drugs, prolonged exposure to environmental toxins, the parasitic infection schistosomiasis, and repeated bouts of heart failure with liver congestion can all lead to cirrhosis.
..
To learn about another disease, click on Digestive diseases Library.
..
..
..
Symptoms
Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:
A. exhaustion
B. fatigue
C. loss of appetite
D. nausea
E. weakness
F. weight loss
G. abdominal pain
H. spider-like blood vessels (spider angiomas) that develop on the skin
...
As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.
...
..
..
A. exhaustion
B. fatigue
C. loss of appetite
D. nausea
E. weakness
F. weight loss
G. abdominal pain
H. spider-like blood vessels (spider angiomas) that develop on the skin
...
As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.
...
To learn about another disease, click on Digestive diseases Library.
..
..
..
Complications of Cirrhosis
Loss of liver function affects the body in many ways.
Following are the common problems, or complications, caused by cirrhosis:
A. Edema and ascites. When the liver loses its ability to make the protein albumin, water accumulates in the legs (edema) and abdomen (ascites).
B. Bruising and bleeding. When the liver slows or stops production of the proteins needed for blood clotting, a person will bruise or bleed easily. The palms of the hands may be reddish and blotchy with palmar erythema.
C. Jaundice. Jaundice is a yellowing of the skin and eyes that occurs when the diseased liver does not absorb enough bilirubin.
D. Itching. Bile products deposited in the skin may cause intense itching.
E. Gallstones. If cirrhosis prevents bile from reaching the gallbladder, gallstones may develop.
F. Toxins in the blood or brain. A damaged liver cannot remove toxins from the blood, causing them to accumulate in the blood and eventually the brain. There, toxins can dull mental functioning and cause personality changes, coma, and even death. Signs of the buildup of toxins in the brain include neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
G. Sensitivity to medication. Cirrhosis slows the liver's ability to filter medications from the blood. Because the liver does not remove drugs from the blood at the usual rate, they act longer than expected and build up in the body. This causes a person to be more sensitive to medications and their side effects.
H. Portal hypertension. Normally, blood from the intestines and spleen is carried to the liver through the portal vein. But cirrhosis slows the normal flow of blood through the portal vein, which increases the pressure inside it. This condition is called portal hypertension.
I. Varices. When blood flow through the portal vein slows, blood from the intestines and spleen backs up into blood vessels in the stomach and esophagus. These blood vessels may become enlarged because they are not meant to carry this much blood. The enlarged blood vessels, called varices, have thin walls and carry high pressure, and thus are more likely to burst. If they do burst, the result is a serious bleeding problem in the upper stomach or esophagus that requires immediate medical attention.
J. Insulin resistance and type 2 diabetes. Cirrhosis causes resistance to insulin. This hormone, produced by the pancreas, enables blood glucose to be used as energy by the cells of the body. If you have insulin resistance, your muscle, fat, and liver cells do not use insulin properly. The pancreas tries to keep up with the demand for insulin by producing more. Eventually, the pancreas cannot keep up with the body's need for insulin, and type 2 diabetes develops as excess glucose builds up in the bloodstream.
K. Liver cancer. Hepatocellular carcinoma, a type of liver cancer commonly caused by cirrhosis, starts in the liver tissue itself. It has a high mortality rate.
L. Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines.
M. impotence,
N. kidney dysfunction and failure, and
O. osteoporosis.
..
..
..
Following are the common problems, or complications, caused by cirrhosis:
A. Edema and ascites. When the liver loses its ability to make the protein albumin, water accumulates in the legs (edema) and abdomen (ascites).
B. Bruising and bleeding. When the liver slows or stops production of the proteins needed for blood clotting, a person will bruise or bleed easily. The palms of the hands may be reddish and blotchy with palmar erythema.
C. Jaundice. Jaundice is a yellowing of the skin and eyes that occurs when the diseased liver does not absorb enough bilirubin.
D. Itching. Bile products deposited in the skin may cause intense itching.
E. Gallstones. If cirrhosis prevents bile from reaching the gallbladder, gallstones may develop.
F. Toxins in the blood or brain. A damaged liver cannot remove toxins from the blood, causing them to accumulate in the blood and eventually the brain. There, toxins can dull mental functioning and cause personality changes, coma, and even death. Signs of the buildup of toxins in the brain include neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
G. Sensitivity to medication. Cirrhosis slows the liver's ability to filter medications from the blood. Because the liver does not remove drugs from the blood at the usual rate, they act longer than expected and build up in the body. This causes a person to be more sensitive to medications and their side effects.
H. Portal hypertension. Normally, blood from the intestines and spleen is carried to the liver through the portal vein. But cirrhosis slows the normal flow of blood through the portal vein, which increases the pressure inside it. This condition is called portal hypertension.
I. Varices. When blood flow through the portal vein slows, blood from the intestines and spleen backs up into blood vessels in the stomach and esophagus. These blood vessels may become enlarged because they are not meant to carry this much blood. The enlarged blood vessels, called varices, have thin walls and carry high pressure, and thus are more likely to burst. If they do burst, the result is a serious bleeding problem in the upper stomach or esophagus that requires immediate medical attention.
J. Insulin resistance and type 2 diabetes. Cirrhosis causes resistance to insulin. This hormone, produced by the pancreas, enables blood glucose to be used as energy by the cells of the body. If you have insulin resistance, your muscle, fat, and liver cells do not use insulin properly. The pancreas tries to keep up with the demand for insulin by producing more. Eventually, the pancreas cannot keep up with the body's need for insulin, and type 2 diabetes develops as excess glucose builds up in the bloodstream.
K. Liver cancer. Hepatocellular carcinoma, a type of liver cancer commonly caused by cirrhosis, starts in the liver tissue itself. It has a high mortality rate.
L. Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines.
M. impotence,
N. kidney dysfunction and failure, and
O. osteoporosis.
..
To learn about another disease, click on Digestive diseases Library.
..
..
..
Diagnosis
..
The doctor may diagnose cirrhosis on the basis of symptoms, laboratory tests, the medical history, and a physical examination. For example:
1. during a physical examination, the doctor may notice that the liver feels harder or larger than usual and order blood tests that can show whether liver disease is present.
2. If looking at the liver is necessary to check for signs of disease, the doctor might order a computerized axial tomography (CAT) scan, ultrasound, magnetic resonance imaging (MRI), or a scan of the liver using a radioisotope (a harmless radioactive substance that highlights the liver). Or the doctor might look at the liver using a laparoscope, an instrument that is inserted through the abdomen and relays pictures back to a computer screen.
3. A liver biopsy will confirm the diagnosis. For a biopsy, the doctor uses a needle to take a tiny sample of liver tissue, then examines it under the microscope for scarring or other signs of disease.
..
..
..
The doctor may diagnose cirrhosis on the basis of symptoms, laboratory tests, the medical history, and a physical examination. For example:
1. during a physical examination, the doctor may notice that the liver feels harder or larger than usual and order blood tests that can show whether liver disease is present.
2. If looking at the liver is necessary to check for signs of disease, the doctor might order a computerized axial tomography (CAT) scan, ultrasound, magnetic resonance imaging (MRI), or a scan of the liver using a radioisotope (a harmless radioactive substance that highlights the liver). Or the doctor might look at the liver using a laparoscope, an instrument that is inserted through the abdomen and relays pictures back to a computer screen.
3. A liver biopsy will confirm the diagnosis. For a biopsy, the doctor uses a needle to take a tiny sample of liver tissue, then examines it under the microscope for scarring or other signs of disease.
..
To learn about another disease, click on Digestive diseases Library.
..
..
..
Treatment for Cirrhosis
..
Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications.
..
Treatment depends on the cause of cirrhosis and any complications a person is experiencing. For example:
..
A. cirrhosis caused by alcohol abuse is treated by abstaining from alcohol.
B. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as:
..1. interferon for viral hepatitis and
..2. corticosteroids for autoimmune hepatitis.
..3. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with medications to remove the copper.
..
These are just a few examples—treatment for cirrhosis resulting from other diseases depends on the underlying cause. In all cases, regardless of the cause, following a healthy diet and avoiding alcohol are essential because the body needs all the nutrients it can get, and alcohol will only lead to more liver damage. Light physical activity can help stop or delay cirrhosis as well.
..
Treatment will also include remedies for complications. For example:
A. for ascites and edema, the doctor may recommend a low-sodium diet or the use of diuretics, which are drugs that remove fluid from the body.
B. Antibiotics will be prescribed for infections,
C. and various medications can help with itching.
D. Protein causes toxins to form in the digestive tract, so eating less protein will help decrease the buildup of toxins in the blood and brain.
E. The doctor may also prescribe laxatives to help absorb the toxins and remove them from the intestines.
F. For portal hypertension, the doctor may prescribe a blood pressure medication such as a beta-blocker.
G. If varices bleed, the doctor may either:
....1. inject them with a clotting agent or
....2. perform a so-called rubber-band ligation, which uses a special device to compress the varices and stop the bleeding.
..
When complications cannot be controlled or when the liver becomes so damaged from scarring that it completely stops functioning, a liver transplant is necessary. In liver transplantation surgery, a diseased liver is removed and replaced with a healthy one from an organ donor. About 80 to 90 percent of patients survive liver transplantation. Survival rates have improved over the past several years because of drugs such as cyclosporine and tacrolimus, which suppress the immune system and keep it from attacking and damaging the new liver.
..
..
..
Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications.
..
Treatment depends on the cause of cirrhosis and any complications a person is experiencing. For example:
..
A. cirrhosis caused by alcohol abuse is treated by abstaining from alcohol.
B. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as:
..1. interferon for viral hepatitis and
..2. corticosteroids for autoimmune hepatitis.
..3. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with medications to remove the copper.
..
These are just a few examples—treatment for cirrhosis resulting from other diseases depends on the underlying cause. In all cases, regardless of the cause, following a healthy diet and avoiding alcohol are essential because the body needs all the nutrients it can get, and alcohol will only lead to more liver damage. Light physical activity can help stop or delay cirrhosis as well.
..
Treatment will also include remedies for complications. For example:
A. for ascites and edema, the doctor may recommend a low-sodium diet or the use of diuretics, which are drugs that remove fluid from the body.
B. Antibiotics will be prescribed for infections,
C. and various medications can help with itching.
D. Protein causes toxins to form in the digestive tract, so eating less protein will help decrease the buildup of toxins in the blood and brain.
E. The doctor may also prescribe laxatives to help absorb the toxins and remove them from the intestines.
F. For portal hypertension, the doctor may prescribe a blood pressure medication such as a beta-blocker.
G. If varices bleed, the doctor may either:
....1. inject them with a clotting agent or
....2. perform a so-called rubber-band ligation, which uses a special device to compress the varices and stop the bleeding.
..
When complications cannot be controlled or when the liver becomes so damaged from scarring that it completely stops functioning, a liver transplant is necessary. In liver transplantation surgery, a diseased liver is removed and replaced with a healthy one from an organ donor. About 80 to 90 percent of patients survive liver transplantation. Survival rates have improved over the past several years because of drugs such as cyclosporine and tacrolimus, which suppress the immune system and keep it from attacking and damaging the new liver.
..
To learn about another disease, click on Digestive diseases Library.
..
..
..
For More Information
..
American Liver Foundation (ALF)
75 Maiden Lane, Suite 603
New York, NY 10038–4810
Phone: 1–800–GO–LIVER (465–4837),
.............1–888–4HEP–USA (443–7872),
..............or 212–668–1000
Fax: 212–483–8179
Email: info@liverfoundation.org
Internet: www.liverfoundation.org
..
Hepatitis Foundation International
504 Blick Drive
Silver Spring, MD 20904–2901
Phone: 1–800–891–0707 or
.............1-301–622–4200
Fax: 301–622–4702
Email: hfi@comcast.net
Internet: www.hepfi.org
..
United Network for Organ Sharing
P.O. Box 2484 Richmond,
VA 23218
Phone: 1–888–894–6361 or
1-804–782–4800
Internet: www.unos.org
..
National Digestive Diseases Information Clearinghouse
2 Information Way
Bethesda, MD 20892–3570
Email: nddic@info.niddk.nih.gov
..
The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases.
..
Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts.
..
This publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired.
..
..
..
American Liver Foundation (ALF)
75 Maiden Lane, Suite 603
New York, NY 10038–4810
Phone: 1–800–GO–LIVER (465–4837),
.............1–888–4HEP–USA (443–7872),
..............or 212–668–1000
Fax: 212–483–8179
Email: info@liverfoundation.org
Internet: www.liverfoundation.org
..
Hepatitis Foundation International
504 Blick Drive
Silver Spring, MD 20904–2901
Phone: 1–800–891–0707 or
.............1-301–622–4200
Fax: 301–622–4702
Email: hfi@comcast.net
Internet: www.hepfi.org
..
United Network for Organ Sharing
P.O. Box 2484 Richmond,
VA 23218
Phone: 1–888–894–6361 or
1-804–782–4800
Internet: www.unos.org
..
National Digestive Diseases Information Clearinghouse
2 Information Way
Bethesda, MD 20892–3570
Email: nddic@info.niddk.nih.gov
..
The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases.
..
Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts.
..
This publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired.
..
To learn about another disease, click on Digestive diseases Library.
..
..
..
Monday, September 11, 2006
Hemochromatosis
Hemochromatosis (Haemochromatosis)
From Wikipedia, the free encyclopedia
Classification and external resources
ICD-10
E83.1
ICD-9
275.0
OMIM
235200 602390 606464 604720 604653
DiseasesDB
5490
eMedicine
med/975 derm/878
MeSH
D006432
Haemochromatosis, also spelled hemochromatosis, also called siderophilia and bronze diabetes, is a hereditary disease characterized by excessive absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like virtually all animals, have no means to excrete excess iron.[1] Excess iron accumulates in tissues and organs disrupting their normal function. The most susceptible organs include the Liver, adrenal glands, the Heart and The Pancreas ; patients can present with Cirrhosis, adrenal insufficiency, heart failure or Diabetes. [2] The hereditary form of the disease is most common among those of Northern European ancestry, in particular those of British or Irish descent.[3]
Haemochromatosis less often refers to the condition of iron overload as a consequence of multiple transfusions. More preferred terms in the United States include for transfusional iron overload or hemosiderosis used synonomously. Those with hereditary anemias such as beta-thalassemia major, sickle cell anemia, and Diamond-Blackfan anemia who require regular transfusions of red blood cells are all at risk for developing life-threatening iron overload. Older patients with various forms of bone marrow failure such as with myelodysplastic syndrome who become transfusion-dependent are also at risk for iron overload.
History
The disease was first described in 1865 by Armand Trousseau in a report on diabetes in patients presenting with a bronze pigmentation of their skin.[4] Trousseau did not associate diabetes with iron accumulation; the recognition that infiltration of the pancreas with iron might disrupt endocrine function resulting in diabetes was made by Friedrich Daniel von Recklinghausen in 1890.[5][6] In 1978 the Iron Overload Diseases Association (IOD) was formed to act as a support group and information center for people affected by hemochromatosis.
Signs and symptoms
Haemochromatosis is protean in its manifestations, i.e., often presenting with signs or symptoms suggestive of other diagnoses that affect specific organ systems. Many of the signs and symptoms below are uncommon and for most patients with the hereditary form of haemochromatosis do not show any overt signs of disease nor do they suffer premature morbidity. [7] The more common clinical manifestations include:[8][9][10]
Diagnosis
The diagnosis of haemochromatosis is often made following the incidental finding on routine blood screening of elevated serum liver enzymes or excessive iron binding saturation of transferrin exceeding the normal value of 50%. Arthropathy with stiff joints, diabetes, or fatigue, may be the presenting complaint. The evaluation of abnormal transferrin saturation commonly involves determining the level of ferritin, a protein found in serum made by liver that binds iron. Serum ferritin in excess of 1000 nanograms per millilitre of blood is almost always attributable to haemochromatosis.[14]
Imaging features
Clinically the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in characteristic findings on unenhanced CT and a decreased signal intensity in MRI scans. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand.[citation needed] The arthropathy can therefore be an early clue as to the diagnosis of haemochromatosis. MRI algorithms are available at research institutions to quantify the amount of iron present in the liver, therefore reducing the necessity of a liver biopsy (see below) to measure the liver iron content. As of May, 2007, this technology was only available at a few sites in the USA, but documented reports of radiographic measurements of liver iron content were becoming more common. [15]
Chemistry
Serum transferrin and transferrin saturation Transferrin binds iron and is responsible for iron transport in the blood.[16] Measuring transferrin provides a crude measure of iron stores in the body. Saturation values in excess of 62% are recognized as a threshold for further evaluation of haemochromatosis. [14]
Serum Ferritin- Ferritin, a protein synthesized by the liver is the primary form of iron storage within cells and tissues. Measuring ferritin provides another crude estimate of whole body iron stores though many conditions notably inflammation can elevate serum ferritin. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml.[14][17] Other blood tests routinely performed:
Based on the history, the doctor might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure, or blood glucose monitoring for patients with haemochromatosis Diabetes.
Histopathology
Iron accumulation demonstrated by Prussian blue staining in a patient with homozygous genetic hemochromatosis (microscopy, 10x magnified). Parts of normal pink tissue are scarcely present." Iron accumulation demonstrated by Prussian blue staining in a patient with homozygous genetic hemochromatosis (microscopy, 10x magnified). Parts of normal pink tissue are scarcely present.
Liver biopsies involve taking a sample of tissue from the liver, using a thin needle. The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, measured microscopically. Formerly, this was the only way to confirm a diagnosis of haemochromatosis but measures of transferrin and ferritin along with a history are considered adequate in determining the presence of the malady. Risks of biopsy include bruising, bleeding and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, it is debatable whether a liver biopsy is still necessary to quantify the amount of accumulated iron.[14]
Screening
Screening specifically means looking for a disease in people who have no symptoms. Diagnosis, on the other hand refers to testing people who have symptoms of a disease. Standard diagnostic measures for haemochromatosis, serum transferrin saturation and serum ferritin tests, are not a part of routine medical testing. Screening for haemochromatosis is recommended if the patient has a parent, child or sibling with the disease, or have any of the following signs and symptoms:[14][18]
Differential diagnosis
There exist other causes of excess iron accumulation, which have to be considered before Haemochromatosis is diagnosed.
Penetrance differs between different populations.
One of the most common cause of hereditary haemochromatosis is a single point mutation at C282Y in which the cystine residue at position 282 is changed into a tyrosine residue.
Recently, a classification has been developed (with chromosome locations):
Description..................OMIM......Mutation.........Locus
______________________________________
Haemochromatosis....235200.....HFE..................6p21.3
type 1: "classical"
-haemochromatosis
Haemochromatosis....602390....hemojuvelin......1q21
type 2A: juvenile.........................("HJV", also
haemochromatosis......................known as HFE2
Haemochromatosis....606464....hepcidin anti-....19q13
type 2B: juvenile........microbial
haemochromatosis.....peptide
......................................(HAMP)
......................................or HFE2B Haemochromatosis....604720....Transferrin........7q22
type 3..........................receptor-2
.....................................TFR2 or HFE3
Haemochromatosis....604653....Ferroportin......2q32
type 4 Autosomal........................(SLC11A3)
dominant(all others
are Recessive gene
____________________________________________________
Pathophysiology
From Wikipedia, the free encyclopedia
Classification and external resources
ICD-10
E83.1
ICD-9
275.0
OMIM
235200 602390 606464 604720 604653
DiseasesDB
5490
eMedicine
med/975 derm/878
MeSH
D006432
Haemochromatosis, also spelled hemochromatosis, also called siderophilia and bronze diabetes, is a hereditary disease characterized by excessive absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like virtually all animals, have no means to excrete excess iron.[1] Excess iron accumulates in tissues and organs disrupting their normal function. The most susceptible organs include the Liver, adrenal glands, the Heart and The Pancreas ; patients can present with Cirrhosis, adrenal insufficiency, heart failure or Diabetes. [2] The hereditary form of the disease is most common among those of Northern European ancestry, in particular those of British or Irish descent.[3]
Haemochromatosis less often refers to the condition of iron overload as a consequence of multiple transfusions. More preferred terms in the United States include for transfusional iron overload or hemosiderosis used synonomously. Those with hereditary anemias such as beta-thalassemia major, sickle cell anemia, and Diamond-Blackfan anemia who require regular transfusions of red blood cells are all at risk for developing life-threatening iron overload. Older patients with various forms of bone marrow failure such as with myelodysplastic syndrome who become transfusion-dependent are also at risk for iron overload.
History
The disease was first described in 1865 by Armand Trousseau in a report on diabetes in patients presenting with a bronze pigmentation of their skin.[4] Trousseau did not associate diabetes with iron accumulation; the recognition that infiltration of the pancreas with iron might disrupt endocrine function resulting in diabetes was made by Friedrich Daniel von Recklinghausen in 1890.[5][6] In 1978 the Iron Overload Diseases Association (IOD) was formed to act as a support group and information center for people affected by hemochromatosis.
Signs and symptoms
Haemochromatosis is protean in its manifestations, i.e., often presenting with signs or symptoms suggestive of other diagnoses that affect specific organ systems. Many of the signs and symptoms below are uncommon and for most patients with the hereditary form of haemochromatosis do not show any overt signs of disease nor do they suffer premature morbidity. [7] The more common clinical manifestations include:[8][9][10]
- Malaise
- Liver cirrhosis (with an increased risk of hepatocellular carcinoma. Liver disease is always preceded by evidence of liver dysfunction including elevated serum enzymes specific to the liver.
- Insulin resistance (often patients have already been diagnosed with diabetes mellitus type 2) due to pancreatic damage from iron deposition
- Erectile dysfunction and hypogonadism
- Decreased libido secondary to the above
- Congestive heart failure, arrhythmias or pericarditis
- Arthritis of the hands (especially the first and second MCP joints), but also the knee and shoulder joints
- Adrenal gland (leading to adrenal insufficiency)
Less common findings including:
- Deafness[11]
- Dyskinesias, including Parkinsonian symptoms[12][11][13]
- Dysfunction of certain endocrine organs:
- Parathyroid gland (leading to hypocalcaemia)
- Pituitary glan
- A darkish colour to the skin (see pigmentation, hence its name Diabetes bronze when it was first described by Armand Trousseau in 1865)
- An increased susceptibility to certain infectious diseases caused by siderophilic microorganisms:
- Vibrio vulnificus infections from eating seafood
- Listeria monocytogenes
- Yersinia enterocolica
- Salmonella enterica (serotype Typhymurium)
- Klebsiella pneumoniae
- Escherichia coli
- Rhizopus arrhizus
- Mucor species
Diagnosis
The diagnosis of haemochromatosis is often made following the incidental finding on routine blood screening of elevated serum liver enzymes or excessive iron binding saturation of transferrin exceeding the normal value of 50%. Arthropathy with stiff joints, diabetes, or fatigue, may be the presenting complaint. The evaluation of abnormal transferrin saturation commonly involves determining the level of ferritin, a protein found in serum made by liver that binds iron. Serum ferritin in excess of 1000 nanograms per millilitre of blood is almost always attributable to haemochromatosis.[14]
Imaging features
Clinically the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in characteristic findings on unenhanced CT and a decreased signal intensity in MRI scans. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand.[citation needed] The arthropathy can therefore be an early clue as to the diagnosis of haemochromatosis. MRI algorithms are available at research institutions to quantify the amount of iron present in the liver, therefore reducing the necessity of a liver biopsy (see below) to measure the liver iron content. As of May, 2007, this technology was only available at a few sites in the USA, but documented reports of radiographic measurements of liver iron content were becoming more common. [15]
Chemistry
Serum transferrin and transferrin saturation Transferrin binds iron and is responsible for iron transport in the blood.[16] Measuring transferrin provides a crude measure of iron stores in the body. Saturation values in excess of 62% are recognized as a threshold for further evaluation of haemochromatosis. [14]
Serum Ferritin- Ferritin, a protein synthesized by the liver is the primary form of iron storage within cells and tissues. Measuring ferritin provides another crude estimate of whole body iron stores though many conditions notably inflammation can elevate serum ferritin. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml.[14][17] Other blood tests routinely performed:
- blood count,
- renal function,
- liver enzymes,
- electrolytes,
- glucose (and/or an oral glucose tolerance test (OGTT)).
Based on the history, the doctor might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure, or blood glucose monitoring for patients with haemochromatosis Diabetes.
Histopathology
Iron accumulation demonstrated by Prussian blue staining in a patient with homozygous genetic hemochromatosis (microscopy, 10x magnified). Parts of normal pink tissue are scarcely present." Iron accumulation demonstrated by Prussian blue staining in a patient with homozygous genetic hemochromatosis (microscopy, 10x magnified). Parts of normal pink tissue are scarcely present.
Liver biopsies involve taking a sample of tissue from the liver, using a thin needle. The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, measured microscopically. Formerly, this was the only way to confirm a diagnosis of haemochromatosis but measures of transferrin and ferritin along with a history are considered adequate in determining the presence of the malady. Risks of biopsy include bruising, bleeding and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, it is debatable whether a liver biopsy is still necessary to quantify the amount of accumulated iron.[14]
Screening
Screening specifically means looking for a disease in people who have no symptoms. Diagnosis, on the other hand refers to testing people who have symptoms of a disease. Standard diagnostic measures for haemochromatosis, serum transferrin saturation and serum ferritin tests, are not a part of routine medical testing. Screening for haemochromatosis is recommended if the patient has a parent, child or sibling with the disease, or have any of the following signs and symptoms:[14][18]
- Joint disease
- Severe fatigue
- Heart disease
- Elevated liver enzymes
- Impotence
- Diabetes
Differential diagnosis
There exist other causes of excess iron accumulation, which have to be considered before Haemochromatosis is diagnosed.
- African iron overload, formerly known as Bantu siderosis, was first observed among people of African descent in Southern Africa. Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer (e.g., African Americans). This led investigators to the discovery of a gene polymorphism in the gene for ferroportin which predisposes some people of African descent to iron overload.[21]
- Transfusion hemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassemia).
- Dyserythropoeisis, also known as myelodysplastic syndrome is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver.
Epidemiology
Haemochromatosis is one of the most common heritable genetic conditions in people of northern European extraction with a prevalence of 1 in 200. The disease has a variable penetration and about 1 in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism, the most common allele being the C282Y allele in the HFE gene. The prevalence of mutations in iron metabolism genes varies in different populations. A study of 3,011 unrelated white Australians found that 14% were heterozygous carriers of an HFE mutation, 0.5% were homozygous for an HFE mutation, and only 0.25% of the study population had clinically relevant iron overload. Most patients who are homozygous for HFE mutations will not manifest clinically relevant haemochromatosis (see genetics below).[22] Other populations have a lower prevalence of both the genetic mutation and the clinical disease. Genetic studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60-70 generations ago. At that time when dietary iron may have been scarcer than today, the presence of the mutant allele may have provided a natural selection reproductive advantage by maintaining higher iron levels in the blood.
Genetics
Haemochromatosis types 1-3 are inherited in an autosomal recessive fashion.
Haemochromatosis types 1-3 are inherited in an autosomal recessive fashion.
The regulation of dietary iron absorption is complex and our understanding is incomplete. One of the better characterized genes responsible for hereditary haemochromatosis is HFE on chromosome 6 which codes for a protein that participates in the regulation of iron absorption. The HFE gene has two common alleles, C282Y and H63D.[23] Heterozygotes for either allele do not manifest clinical iron overload but may display an increased iron uptake. Mutations of the HFE gene account for 90% of the cases of non-transfusional iron overload. This gene is closely linked to the HLA-A3 locus. Homozygosity for the C282Y mutation is the most common genotype responsible for clinical iron accumulation, though heterozygosity for C282Y/H63D mutations, so-called compound heterozygotes, results in clinically evident iron overload. There is considerable debate regarding the penetrance -- the probability of clinical expression of the trait given the genotype -- is for clinical disease in HHC homozygotes. Most, if not all, males homozygous for HFE C282Y will show manifestations of liver dysfunction such as elevated liver-specific enzymes such as serum gamma glutamyltransferase (GGT) by late middle age. Homozygous females can delay the onset of iron accumulation because of iron loss through menstruation. Each patient with the susceptible genotype accumulates iron at different rates depending on iron intake, the exact nature of the mutation and the presence of other insults to the liver such as alcohol and viral disease. As such the degree to which the liver and other organs is affected, expressivity, is highly variable and is dependent on such these other factors and co-morbidities as well as age at which they are studied for manifestations of disease.[22]
Penetrance differs between different populations.
One of the most common cause of hereditary haemochromatosis is a single point mutation at C282Y in which the cystine residue at position 282 is changed into a tyrosine residue.
Recently, a classification has been developed (with chromosome locations):
Description..................OMIM......Mutation.........Locus
______________________________________
Haemochromatosis....235200.....HFE..................6p21.3
type 1: "classical"
-haemochromatosis
Haemochromatosis....602390....hemojuvelin......1q21
type 2A: juvenile.........................("HJV", also
haemochromatosis......................known as HFE2
Haemochromatosis....606464....hepcidin anti-....19q13
type 2B: juvenile........microbial
haemochromatosis.....peptide
......................................(HAMP)
......................................or HFE2B Haemochromatosis....604720....Transferrin........7q22
type 3..........................receptor-2
.....................................TFR2 or HFE3
Haemochromatosis....604653....Ferroportin......2q32
type 4 Autosomal........................(SLC11A3)
dominant(all others
are Recessive gene
____________________________________________________
Pathophysiology
The normal distribution of body iron stores
Since the regulation of iron metabolism is still poorly understood, a clear model of how haemochromatosis operates is still not available as of May, 2007. For example, HFE is only part of the story, since many patients with mutated HFE do not manifest clinical iron overload, and some patients with iron overload have a normal HFE genotype. A possible explanation is the fact that HFE normally plays a role in the production of hepcidin in the liver, a function that is impaired in HFE mutations.[24]
People with abnormal iron regulatory genes do not reduce their absorption of iron in response to increased iron levels in the body. Thus the iron stores of the body increase. As they increase the iron which is initially stored as ferritin is deposited in organs as haemosiderin and this is toxic to tissue, probably at least partially by inducing oxidative stress.[25]. Iron is a pro-oxidant. Thus, haemochromatosis shares common symptomology (e.g., cirrhosis and dyskinetic symptoms) with other "pro-oxidant" diseases such as Wilson's disease, chronic manganese poisoning, and hyperuricaemic syndrome in Dalmatian dogs. The latter also experience "bronzing".
Intestinal crypt enterocytes and iron overload
The sensor pathway inside the small bowel enterocyte can be disrupted due to genetic errors in the iron regulatory apparatus. The enterocyte in the small bowel crypt must somehow sense the amount of circulating iron. Depending on this information, the enterocyte cell can regulate the quantity of iron receptors and channel proteins. If there is little iron, the enterocyte cell will express many of these proteins. If there is a lot, the cell will turn off the expression of iron transporters. In haemochromatosis, a mutation in the HFE gene leads to a lack of the basolateral transporter that endocytoses iron from the plasma into the epithelial cell. As a consequence of being unable to detect serum iron concentrations, it overexpresses the necessary channel proteins, this leading to a massive, and unnecessary iron absorption. These iron transport proteins are named DMT-1 (divalent metal transporter), for the luminal side of the cell, and ferroportin, the only known cellular iron exporter, for the basal side of the cell.
Hepcidin-ferroportin axis and iron overload
Recently, a new unifying theory for the pathogenesis of hereditary haemochromatosis has been proposed that focuses on the hepcidin-ferroportin regulatory axis. Inappropriately low levels of hepcidin, the iron regulatory hormone, can account for the clinical phenotype of iron overload. In this theory, low levels of circulating hepcidin result in higher levels of ferroportin expression in intestinal enterocytes and reticuloendothelial macrophages. As a result, this causes iron accumulation. HFE, hemojuvelin, BMP's and TFR2 are implicated in regulating hepcidin expression. In particular, mutations in hemojuvelin (HJV), also called RGMc (Repulsive Guidance Molecule c), result in a severe form of iron overload that has a juvenile onset (by the second decade of life) called juvenile haemochromatosis (JH).
[edit] End-organ damage
Iron is stored in the liver, the pancreas and the heart. Long term effects of haemochromatosis on these organs can be very serious, even fatal when untreated.[26] For example, similar to alcoholism, haemochromatosis can cause cirrhosis of the liver. The liver is a primary storage area for iron and will naturally accumulate excess iron. Over time the liver is likely to be damaged by iron overload. Cirrhosis itself may lead to additional and more serious complications, including bleeding from dilated veins in the oesophagus and stomach (varices) and severe fluid retention in the abdomen (ascites). Toxins may accumulate in the blood and eventually affect mental functioning. This can lead to confusion or even coma (hepatic encephalopathy).
Liver cancer: Cirrhosis and haemochromatosis together will increase the risk of liver cancer. (Nearly one-third of people with haemochromatosis and cirrhosis eventually develop liver cancer.)
Diabetes: The pancreas which also stores iron is very important in the body’s mechanisms for sugar metabolism. Diabetes affects the way the body uses blood sugar (glucose). Diabetes is in turn the leading cause of new blindness in adults and may be involved in kidney failure and cardiovascular disease.
Congestive heart failure: If excess iron in the heart interferes with the its ability to circulate enough blood, a number of problems can occur including death. The condition may be reversible when haemochromatosis is treated and excess iron stores reduced.
Heart arrhythmias: Arrhythmia or abnormal heart rhythms can cause heart palpitations, chest pain and light-headedness and are occasionally life threatening. This condition can often be reversed with treatment for haemochromatosis.
Pigment changes: Deposits of iron in skin cells can turn skin a bronze or gray color.
[edit] Treatment
Early diagnosis is important because the late effects of iron accumulation can be wholly prevented by periodic phlebotomies (by venesection) comparable in volume to blood donations.[27] Treatment is initiated when ferritin levels reach 300 milligrams per litre (or 200 in nonpregnant premenopausal women).
Every bag of blood (450-500 ml) contains 200-250 milligrams of iron. Phlebotomy (or bloodletting) is usually done at a weekly interval until ferritin levels are less than 20 milligrams per litre. After that, 1-4 donations per year are usually needed to maintain iron balance.
Other parts of the treatment include:
Treatment of organ damage (heart failure with diuretics and ACE inhibitor therapy).
Limiting intake of alcoholic beverages, vitamin C (increases iron absorption in the gut), red meat (high in iron) and potential causes of food poisoning (shellfish, seafood).
Increasing intake of substances that inhibit iron absorption, such as high-tannin tea, calcium, and foods containing oxalic and phytic acids (such as spinach or collard greens, which must be consumed at the same time as the iron-containing foods in order to be effective.)
[edit] References
^ "The interaction of iron and erythropoietin".
^ Iron Overload and Hemochromatosis Centers for Disease Control and Prevention
^ "Celtic Curse".
^ Trousseau A (1865). "Glycosurie, diabète sucré". Clinique médicale de l'Hôtel-Dieu de Paris 2: 663–98.
^ von Recklinghausen FD (1890). "Hämochromatose". Tageblatt der Naturforschenden Versammlung 1889: 324.
^ Biography of Daniel von Recklinghausen
^ Hemochromatosis-Diagnosis National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services
^ Iron Overload and Hemochromatosis Centers for Disease Control and Prevention
^ Hemochromatosis National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services
^ "Hemochromatosis: Symptoms". Mayo Foundation for Medical Education and Research (MFMER).
^ a b Jones H, Hedley-Whyte E (1983). "Idiopathic hemochromatosis (IHC): dementia and ataxia as presenting signs". Neurology 33 (11): 1479–83. PMID 6685241.
^ Costello D, Walsh S, Harrington H, Walsh C (2004). "Concurrent hereditary haemochromatosis and idiopathic Parkinson's disease: a case report series". J Neurol Neurosurg Psychiatry 75 (4): 631–3. doi:10.1136/jnnp.2003.027441. PMID 15026513.
^ Nielsen J, Jensen L, Krabbe K (1995). "Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome". J Neurol Neurosurg Psychiatry 59 (3): 318–21. PMID 7673967.
^ a b c d e "Hemochromatosis: Tests and diagnosis". Mayo Foundation for Medical Education and Research (MFMER).
^ Tanner MA, He T, Westwood MA, Firmin DN, Pennell DJ (2006). "Multi-center validation of the transferability of the magnetic resonance T2* technique for the quantification of tissue iron". Haematologica 91 (10): 1388–91. PMID 17018390.
^ Transferrin and Iron Transport Physiology
^ MedlinePlus Encyclopedia Ferritin Test Measuring iron in the body
^ "Summaries for patients. Screening for hereditary hemochromatosis: recommendations from the American College of Physicians" (2005). Ann. Intern. Med. 143 (7): I46. PMID 16204158.
^ "Screening for haemochromatosis: recommendation statement" (2006). Ann. Intern. Med. 145 (3): 204–8. PMID 16880462.
^ Screening for Hemochromatosis U.S. Preventive Services Task Force (2006). Summary of Screening Recommendations and Supporting Documents. Retrieved 18 March, 2007
^ Gordeuk V, Caleffi A, Corradini E, Ferrara F, Jones R, Castro O, Onyekwere O, Kittles R, Pignatti E, Montosi G, Garuti C, Gangaidzo I, Gomo Z, Moyo V, Rouault T, MacPhail P, Pietrangelo A (2003). "Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene". Blood Cells Mol Dis 31 (3): 299–304. doi:10.1016/S1079-9796(03)00164-5. PMID 14636642.
^ a b Olynyk J, Cullen D, Aquilia S, Rossi E, Summerville L, Powell L (1999). "A population-based study of the clinical expression of the hemochromatosis gene". N Engl J Med 341 (10): 718–24. doi:10.1056/NEJM199909023411002. PMID 10471457.
^ "Hemochromatosis: Causes". Mayo Foundation for Medical Education and Research (MFMER).
^ Vujić Spasić M, Kiss J, Herrmann T, et al (2008). "Hfe acts in hepatocytes to prevent hemochromatosis". Cell Metab. 7 (2): 173–8. doi:10.1016/j.cmet.2007.11.014. PMID 18249176.
^ Shizukuda Y, Bolan C, Nguyen T, Botello G, Tripodi D, Yau Y, Waclawiw M, Leitman S, Rosing D (2007). "Oxidative stress in asymptomatic subjects with hereditary hemochromatosis". Am J Hematol 82 (3): 249–50. doi:10.1002/ajh.20743. PMID 16955456.
^ "Hemochromatosis: Complications". Mayo Foundation for Medical Education and Research (MFMER).
^ "Hemochromatosis: Treatments and drugs". Mayo Foundation for Medical Education and Research (MFMER).
[edit] See also
Cirrhosis
[edit] External links
Haemochromatosis at the Open Directory Project
[show]
v • d • ePathology: hematology · myeloid hematologic disease (primarily D50-D77 · 280-289)
RBCs/hemoglobinopathy
+
Polycythemia · Macrocytosis
·
Anemia
Nutritional
Iron deficiency anemia (Plummer-Vinson syndrome) · Megaloblastic anemia (Pernicious anemia)
Hemolytic
Hereditary
enzyme: G6PD Deficiency · Pyruvate kinase deficiency · Triosephosphate isomerase deficiency
hemoglobin: Thalassemia · Sickle-cell disease/traitmembrane: Hereditary spherocytosis · Hereditary elliptocytosis · Hereditary stomatocytosis
Acquired
Autoimmune (Warm, Cold) · HUS · MAHA · PNH · PCH · Myelophthisic
Aplastic
Acquired PRCA · Diamond-Blackfan anemia · Fanconi anemia · Sideroblastic anemia
Blood tests
Normocytic · Microcytic · Macrocytic · Normochromic · Hypochromic
Other
Methemoglobinemia
Coagulation/platelets/coagulopathy/bleeding diathesis
+
Hypercoagulability
primary: Antithrombin III deficiency · Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden · Hyperprothrombinemiaacquired: DIC (Congenital afibrinogenemia, Purpura fulminans) · autoimmune (Antiphospholipid)
Other
Essential thrombocytosis
·
clotting factor: Hemophilia (A/VIII, B/IX, C/XI) • Von Willebrand disease • Hypoprothrombinemia/II · XIII
platelet function: Bernard-Soulier syndrome · Glanzmann's thrombasthenia · Hermansky-Pudlak syndrome · Gray platelet syndrome · May Hegglin anomaly · Pelger-Huet anomaly
Purpura: Henoch-Schönlein · TP · ITP (Evans syndrome) · TTPThrombocytopenia (Heparin-induced thrombocytopenia)
Monocytes/macrophages
+
Histiocytosis
WHO-I (Langerhans cell histiocytosis)
WHO-II/non-Langerhans-cell (Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis)WHO-III/malignant (Acute monocytic leukemia, Malignant histiocytosis, Erdheim-Chester disease)
Other
Chronic granulomatous disease-cytosis: Monocytosis
·
-penia: Monocytopenia
Granulocytes
+
-cytosis: granulocytosis (Neutrophilia, Eosinophilia, Basophilia)
·
-penia: Granulocytopenia/agranulocytosis (Neutropenia/Kostmann syndrome · Eosinopenia · Basopenia)
See also hematological malignancy and immune disorders
[show]
v • d • eInborn errors of metal metabolism (E83, 275)
Cu
Wilson's disease - Menkes disease
Fe
Primary iron overload disorder: Haemochromatosis (Juvenile) - Aceruloplasminemia - Atransferrinemia - Hemosiderosis
Zn
Acrodermatitis enteropathica
PO43−
Hyperphosphatemia - Hypophosphatemia - Hypophosphatasia
Mg2+
Hypermagnesemia - Hypomagnesemia
Ca2+
Hypercalcaemia - Hypocalcaemia - Pseudohypoparathyroidism - Pseudopseudohypoparathyroidism - Milk-alkali syndrome (Burnett's) - Calcinosis (Calciphylaxis, Calcinosis cutis) - Calcification (Metastatic calcification, Dystrophic calcification)
Retrieved from "http://en.wikipedia.org/wiki/Haemochromatosis"
Categories: Hematology Metabolic disorders Arthritis Gastroenterology Genetic disorders Hepatology Iron
Hidden categories: Cleanup from January 2008 All pages needing cleanup All articles with unsourced statements Articles with unsourced statements since March 2007
To read information on other diseases, click on Digestive Diseases Library
Subscribe to:
Posts (Atom)
