Hepatic encephalopathy pathophysiology: Difference between revisions
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== Associated Conditions == | == Associated Conditions == | ||
Any disorders with liver failure may lead to hepatic encephalopathy. | Any disorders with liver failure may lead to hepatic encephalopathy. | ||
* Disorders and conditions which may lead to hepatic encephalopathy include:<ref name="pmid18328931">{{cite journal| author=Schuppan D, Afdhal NH| title=Liver cirrhosis. | journal=Lancet | year= 2008 | volume= 371 | issue= 9615 | pages= 838-51 | pmid=18328931 | doi=10.1016/S0140-6736(08)60383-9 | pmc=2271178 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18328931 }} </ref><ref name="pmid24833875">{{cite journal| author=Nusrat S, Khan MS, Fazili J, Madhoun MF| title=Cirrhosis and its complications: evidence based treatment. | journal=World J Gastroenterol | year= 2014 | volume= 20 | issue= 18 | pages= 5442-60 | pmid=24833875 | doi=10.3748/wjg.v20.i18.5442 | pmc=4017060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24833875 }} </ref><ref name="pmid24966602">{{cite journal| author=Zhou WC, Zhang QB, Qiao L| title=Pathogenesis of liver cirrhosis. | journal=World J Gastroenterol | year= 2014 | volume= 20 | issue= 23 | pages= 7312-24 | pmid=24966602 | doi=10.3748/wjg.v20.i23.7312 | pmc=4064077 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24966602 }} </ref><ref name="pmid25525477">{{cite journal| author=Nguyen DL, Morgan T| title=Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view. | journal=Hepatol Int | year= 2014 | volume= 8 | issue= 2 | pages= 447-51 | pmid=25525477 | doi=10.1007/s12072-013-9497-1 | pmc=4267851 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25525477 }} </ref><ref name="pmid28533911">{{cite journal| author=Ferenci P| title=Hepatic encephalopathy. | journal=Gastroenterol Rep (Oxf) | year= 2017 | volume= 5 | issue= 2 | pages= 138-147 | pmid=28533911 | doi=10.1093/gastro/gox013 | pmc=5421503 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28533911 }} </ref> | * Disorders and conditions which may lead to hepatic encephalopathy include:<ref name="pmid18328931">{{cite journal| author=Schuppan D, Afdhal NH| title=Liver cirrhosis. | journal=Lancet | year= 2008 | volume= 371 | issue= 9615 | pages= 838-51 | pmid=18328931 | doi=10.1016/S0140-6736(08)60383-9 | pmc=2271178 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18328931 }} </ref><ref name="pmid24833875">{{cite journal| author=Nusrat S, Khan MS, Fazili J, Madhoun MF| title=Cirrhosis and its complications: evidence based treatment. | journal=World J Gastroenterol | year= 2014 | volume= 20 | issue= 18 | pages= 5442-60 | pmid=24833875 | doi=10.3748/wjg.v20.i18.5442 | pmc=4017060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24833875 }} </ref><ref name="pmid24966602">{{cite journal| author=Zhou WC, Zhang QB, Qiao L| title=Pathogenesis of liver cirrhosis. | journal=World J Gastroenterol | year= 2014 | volume= 20 | issue= 23 | pages= 7312-24 | pmid=24966602 | doi=10.3748/wjg.v20.i23.7312 | pmc=4064077 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24966602 }} </ref><ref name="pmid25525477">{{cite journal| author=Nguyen DL, Morgan T| title=Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view. | journal=Hepatol Int | year= 2014 | volume= 8 | issue= 2 | pages= 447-51 | pmid=25525477 | doi=10.1007/s12072-013-9497-1 | pmc=4267851 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25525477 }} </ref><ref name="pmid28533911">{{cite journal| author=Ferenci P| title=Hepatic encephalopathy. | journal=Gastroenterol Rep (Oxf) | year= 2017 | volume= 5 | issue= 2 | pages= 138-147 | pmid=28533911 | doi=10.1093/gastro/gox013 | pmc=5421503 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28533911 }} </ref><ref name="pmid11726084">{{cite journal| author=Klempnaue J, Schrem H| title=Review: surgical shunts and encephalopathy. | journal=Metab Brain Dis | year= 2001 | volume= 16 | issue= 1-2 | pages= 21-5 | pmid=11726084 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11726084 }} </ref> | ||
** [[Alcoholic liver disease]] | ** [[Alcoholic liver disease]] | ||
**[[Hepatitis C]] | **[[Hepatitis C]] | ||
Revision as of 17:48, 12 December 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]
Overview
Due to the presence of scarring within the liver, cirrhosis leads to obstruction of the passage of blood through the liver causing portal hypertension. This means it is difficult for blood from the intestines to go through the liver to get back to the heart. Portal-systemic anastamoses ("shunts") develop, and portal blood (from the intestinal veins) will bypass the liver and return to the heart via another route without undergoing first-pass detoxification by the liver. The toxic substances which accumulate in the setting of liver failure and affect the brain have been thought to include ammonia (NH3) and mercaptans. Ammonia is normally converted to urea by the liver and, as with mercaptans, is produced by the bacterial breakdown of protein in the intestines. Ammonia can cross the blood-brain barrier, where it causes the support cells of the brain (astrocytes) to swell. The swelling of the brain tissue increases intracranial pressure, and can lead to coma or death via herniation of the brainstem. Disorders and conditions such as alcoholic liver disease, hepatitis C, hepatitis B, hemochromatosis, Wilson disease, age above 50 years and male gender may lead to hepatic encephalopathy.
Pathophysiology
Pathogenesis
Following important aspects about pathophysiology of hepatic encephalopathy need to be understood:[1][2][3][4]
Due to the presence of scarring within the liver, cirrhosis leads to obstruction of the passage of blood through the liver causing portal hypertension. This means it is difficult for blood from the intestines to go through the liver to get back to the heart. Portal-systemic anastamoses ("shunts") develop, and portal blood (from the intestinal veins) will bypass the liver and return to the heart via another route without undergoing first-pass detoxification by the liver.
Furthermore, in cirrhosis and other forms of liver disease, the damaged liver will not be functioning as well as it should be, so even blood that does travel through the liver may not be as detoxified as it otherwise would be. In fact, if the degree of liver damage and malfunction is severe, then, even in the absence of portal hypertension and the consequent bypassing of the liver by blood coming in from the intestines, hepatic encephalopathy will still occur. Such may well be the case, for example, following severe injury due to acetaminophen poisoning or acute viral infection (e.g. hepatitis A).
The toxic substances which accumulate in the setting of liver failure and affect the brain are still not well understood. They have been thought to include ammonia (NH3) and mercaptans. Ammonia is normally converted to urea by the liver and, as with mercaptans, is produced by the bacterial breakdown of protein in the intestines.
Ammonia can cross the blood-brain barrier, where it causes the support cells of the brain (astrocytes) to swell. The swelling of the brain tissue increases intracranial pressure, and can lead to coma or death via herniation of the brainstem.
Genetics
There is no established relation between hepatic encephalopathy and genetic inheritance.
Associated Conditions
Any disorders with liver failure may lead to hepatic encephalopathy.
- Disorders and conditions which may lead to hepatic encephalopathy include:[5][6][7][8][9][10]
- Alcoholic liver disease
- Hepatitis C
- Hepatitis B
- Hemochromatosis
- Wilson’s disease
- Age above 50 years
- Male gender
- Eating too much protein
- Bleeding from the intestines, stomach, or esophagus
- Shunt placement or complications (Transjugular intrahepatic portosystemic shunt)
Microscopic Pathology
Microscopic studies of specimens from patients with hepatic encephalopathy suggests:[3]
- Astrocytic changes
- Cellular swelling.
References
- ↑ Frederick RT (2011). "Current concepts in the pathophysiology and management of hepatic encephalopathy". Gastroenterol Hepatol (N Y). 7 (4): 222–33. PMC 3127024. PMID 21857820.
- ↑ Jones EA (2000). "Pathogenesis of hepatic encephalopathy". Clin Liver Dis. 4 (2): 467–85. PMID 11232201.
- ↑ 3.0 3.1 Cordoba J (2014). "Hepatic Encephalopathy: From the Pathogenesis to the New Treatments". ISRN Hepatol. 2014: 236268. doi:10.1155/2014/236268. PMC 4890879. PMID 27335836.
- ↑ Aldridge DR, Tranah EJ, Shawcross DL (2015). "Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation". J Clin Exp Hepatol. 5 (Suppl 1): S7–S20. doi:10.1016/j.jceh.2014.06.004. PMC 4442852. PMID 26041962.
- ↑ Schuppan D, Afdhal NH (2008). "Liver cirrhosis". Lancet. 371 (9615): 838–51. doi:10.1016/S0140-6736(08)60383-9. PMC 2271178. PMID 18328931.
- ↑ Nusrat S, Khan MS, Fazili J, Madhoun MF (2014). "Cirrhosis and its complications: evidence based treatment". World J Gastroenterol. 20 (18): 5442–60. doi:10.3748/wjg.v20.i18.5442. PMC 4017060. PMID 24833875.
- ↑ Zhou WC, Zhang QB, Qiao L (2014). "Pathogenesis of liver cirrhosis". World J Gastroenterol. 20 (23): 7312–24. doi:10.3748/wjg.v20.i23.7312. PMC 4064077. PMID 24966602.
- ↑ Nguyen DL, Morgan T (2014). "Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view". Hepatol Int. 8 (2): 447–51. doi:10.1007/s12072-013-9497-1. PMC 4267851. PMID 25525477.
- ↑ Ferenci P (2017). "Hepatic encephalopathy". Gastroenterol Rep (Oxf). 5 (2): 138–147. doi:10.1093/gastro/gox013. PMC 5421503. PMID 28533911.
- ↑ Klempnaue J, Schrem H (2001). "Review: surgical shunts and encephalopathy". Metab Brain Dis. 16 (1–2): 21–5. PMID 11726084.