Cholestasis commonly presents with jaundice, pale stools and dark urine. There may be abdominal pain and fever in case of infection or cholecystitis. A common feature of cholestasis is pruritus, which may be disabling or significantly affecting the daily life of the patient. Children may show failure to thrive, hormonal disturbances, and attention deficits. Sometimes, xanthomas may be observed on the trunk and diaper area and in skin folds [8].

• Pain

  The most common symptoms are: Overall itching, especially the palms of the hands and soles of the feet Mild nausea and pain in the upper right part of the belly Dark urine color Light coloring of stools (bowel movements) Easy bleeding Chills Pain from [choc.org]

  Findings that suggest a cause outside the liver include certain kinds of abdominal pain (such as intermittent pain in the upper right side of the abdomen and sometimes also in the right shoulder) and an enlarged gallbladder (felt during the physical examination [msdmanuals.com]

  The most common initial symptoms include fever, dysuria, abdominal pain, and flank pain. The most frequent organ system involvement is hematologic and renal. [omicsonline.org]

  Pains can be mild or intense, depending on the severity of the condition. [ddc.musc.edu]

  Jaundice, pruritus, nausea, vomiting, and pain are frequent symptoms. Management consists of treatment of underlying cause and treatment of pruritus. [symptoma.com]

• Sepsis

  Cholestasis is a common complication of sepsis, and the increased plasma levels of bile acids are predictive of sepsis-associated mortality. However, the exact mechanism by which cholestasis aggravates sepsis development remains elusive. [ncbi.nlm.nih.gov]

  Complications may include: Diarrhea Organ failure can occur if sepsis develops Poor absorption of fat and fat-soluble vitamins Severe itching Weak bones (osteomalacia) due to having cholestasis for a very long time Call your health care provider if you [medlineplus.gov]

  To investigate sepsis Presence of sepsis from a source other than the biliary tree. To investigate total parenteral nutrition (TPN): History of TPN administration for more than 2-3 weeks. [hepatitis.va.gov]

• Falling

  Consequences of itching included skin damage (78%), mood changes (59%), and difficulties staying asleep (59%) or falling asleep (53%). [ncbi.nlm.nih.gov]

  It is usually measured every few weeks to monitor trends and detect if the level is rising, falling or stabilising. As part of the ongoing monitoring the blood clotting times are measured. [irishhealth.com]

  Benign intrahepatic cholestasis of pregnancy falls into this category. [patient.info]

  To make squares disappear and save space for other squares you have to assemble English words (left, right, up, down) from the falling squares. boggle Boggle gives you 3 minutes to find as many words (3 letters or more) as you can in a grid of 16 letters [dictionary.sensagent.com]

  By this point I was also sick of wearing a monitor so they tried to clip one to Kate’s head, which kept falling off. The reinforcement midwife, upon clipping it on a second time, said if I wanted to push I could give it a go. So I did. [mumsdays.com]

• Swelling

  Cholangitis is inflammation (swelling and redness) in the bile duct. The American Liver Foundation notes that cholangitis is a type of liver disease. [healthline.com]

• Anemia

  Anti-C(w) may lead to severe fetal anemia and consecutive complications. [ncbi.nlm.nih.gov]

  Hematology screen may show anemia in case of malignancy. Leukocytosis is present in case of infection. Cholestasis often leads to abnormally shaped cells. [symptoma.com]

  Labs were remarkable for a profound leukocytosis, anemia, cholestasis, and an elevated creatinine. An abdominal ultrasound did not reveal cholecystitis or a common bile duct obstruction. [omicsonline.org]

  Other risk factors include: a history of gallstones chronic pancreatitis pancreatic cancer an injury to the right part of the abdomen obesity rapid weight loss conditions related to the breakdown of red blood cells, such as sickle cell anemia Various [healthline.com]

• Nausea

  […] and other penicillins Anabolic steroids Birth control pills Chlorpromazine Cimetidine Estradiol Imipramine Prochlorperazine Terbinafine Tolbutamide Symptoms may include: Clay-colored or white stools Dark urine Inability to digest certain foods Itching Nausea [medlineplus.gov]

  Some women experience fatigue, nausea or abdominal discomfort. What other problems can occur with it? This condition is potentially serious for the unborn baby with an increased risk of foetal distress, preterm labour and stillbirth. [dermcoll.edu.au]

  It can also be accompanied by: jaundice pale stools dark urine abdominal pain nausea See your doctor if you have itching in pregnancy. [healthline.com]

  The most common symptoms are: Overall itching, especially the palms of the hands and soles of the feet Mild nausea and pain in the upper right part of the belly Dark urine color Light coloring of stools (bowel movements) Easy bleeding Chills Pain from [choc.org]

• Diarrhea

  Extrahepatic features have been reported including persistent short stature, watery diarrhea, pancreatitis and sensorineural deafness. [orpha.net]

  Complications may include: Diarrhea Organ failure can occur if sepsis develops Poor absorption of fat and fat-soluble vitamins Severe itching Weak bones (osteomalacia) due to having cholestasis for a very long time Call your health care provider if you [medlineplus.gov]

  Possible Complications Complications may include: Diarrhea Organ failure can occur if sepsis develops Poor absorption of fat and fat-soluble vitamins Severe itching Weak bones (osteomalacia) due to having cholestasis for a very long time Prevention Get [account.allinahealth.org]

  It shows intermittent symptoms such as chronic or intermittent jaundice,abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy,alcoholism, surgical procedures and intercurrent disease. [kci.go.kr]

• Clay-Colored Stool

  Jaundice and Intrahepatic cholestasis of pregnancy (ICP) The increased build-up of bilirubin leads to jaundice, dark colored urine and pale white clay colored stool. This may be seen in very few severe cases of ICP. [news-medical.net]

  Dark urine and clay-colored stools. Nausea and vomiting. Yellowing of the skin (jaundice), which may come and go. Quick diagnosis and treatment are very important. Antibiotics to cure infection are the first treatment done in most cases. [medlineplus.gov]

  Symptoms Symptoms may include: abdominal pain in the upper right area of the gut fever and chills clay-colored stools dark urine nausea and vomiting jaundice (a yellow tinge that appears in the eyes and on the skin) Pain can be intermittent, and may also [ddc.musc.edu]

  Symptoms may include: Pain in the upper right part of your belly (abdomen) Fever Chills Yellowing of the skin and eyes (jaundice) Nausea and vomiting Clay-colored stools Dark urine Low blood pressure Lethargy Not as alert The symptoms of cholangitis may [urmc.rochester.edu]

• Jaundice

  Jaundice. Jaundice is an uncommon occurrence in intrahepatic (metabolic) cholestasis, but is common in obstructive cholestasis. Pale stool. This symptom implies obstructive cholestasis. [en.wikipedia.org]

  Intrahepatic cholestasis of pregnancy Also known as recurrent cholestasis of pregnancy, obstetric cholestasis, cholestasis of pregnancy, recurrent jaundice of pregnancy, cholestatic jaundice of pregnancy, idiopathic jaundice of pregnancy, prurigo gravidarum [dermcoll.edu.au]

  Evaluation of Jaundice in Adults. Am Fam Physician. 2017 Feb 01;95(3):164-168. [PubMed: 28145671] 5. Robie DK, Overfelt SR, Xie L. Differentiating biliary atresia from other causes of cholestatic jaundice. Am Surg. 2014 Sep;80(9):827-31. [ncbi.nlm.nih.gov]

  However, their exact role in the pathogenesis of jaundice-related nephropathy is not known. [acgcasereports.gi.org]

• Hepatomegaly

  For diagnosis of BA, clinical evaluation, hepatomegaly, stool color, serum gamma-glutamyltranspeptidase (GGT), duodenal juice color, bile acid in duodenal juice, ultrasonography (gallbladder), ultrasonography (griangular cord or strip-apparent hyperechoic [ncbi.nlm.nih.gov]

  Clinical signs of cholestasis (discolored stools, dark urine) usually appear in the first months of life with recurrent or permanent jaundice associated with hepatomegaly and severe pruritus. [orpha.net]

  They later develop firm hepatomegaly and splenomegaly. [emjreviews.com]

• Scleral Icterus

  Her physical exam was remarkable for jaundice and scleral icterus without any stigmata of liver disease. [ncbi.nlm.nih.gov]

  It results in jaundice, which can be detected by scleral icterus at a concentration as low as 2 mg/dL, and by dark urine. [emedicine.medscape.com]

  Exam revealed a chronically ill-appearing man with a flat affect, scleral icterus, and pronounced jaundice. He was well-oriented to questions but displayed asterixis. [acgcasereports.gi.org]

• Biliary Colic

  These stones cause biliary colic, biliary obstruction, gallstone pancreatitis, or cholangitis (bile duct infection and inflammation). Cholangitis, in turn, can lead to strictures, stasis, and choledocholithiasis. [merckmanuals.com]

  Hepatitis Consequences Jaundice Pruritus Biliary colic Ascending cholangitis Blood culture. Malabsorption, especially Vitamin K deficiency Osteomalacia Biliary cirrhosis [rcpa.edu.au]

  The clinical features of cholangitis are very similar to other biliary pathologies. A biliary colic will present with a colicky RUQ pain yet without fever, leucocytosis, or jaundice. [teachmesurgery.com]

  For related pathophysiology, please see the Cholelithiasis and Cholecystitis and Biliary Colic articles. [emedicine.medscape.com]

• Recurrent Jaundice

  Intrahepatic cholestasis of pregnancy Also known as recurrent cholestasis of pregnancy, obstetric cholestasis, cholestasis of pregnancy, recurrent jaundice of pregnancy, cholestatic jaundice of pregnancy, idiopathic jaundice of pregnancy, prurigo gravidarum [dermcoll.edu.au]

  Keywords Bile Acid Primary Biliary Cirrhosis Primary Sclerosing Cholangitis Intrahepatic Cholestasis Serum Bile Acid Disease name and synonyms Intrahepatic cholestasis of pregnancy Obstetric cholestasis Recurrent jaundice of pregnancy Pruritus gravidarum [ojrd.biomedcentral.com]

• Pruritus

  Intractable pruritus of cholestasis leads to significant morbidity. [ncbi.nlm.nih.gov]

  Signs and symptoms[edit] Itchiness (pruritus). Pruritus is the primary symptom of cholestasis and is thought to be due to interactions of serum bile acids with opioidergic nerves. [en.wikipedia.org]

  Ultraviolet B phototherapy has been successfully used to treat pruritus. [emedicine.medscape.com]

• Excoriation

  There is no rash but the skin may show scratch marks (excoriations) or become yellow (jaundiced). This condition typically develops late in pregnancy and resolves within days after the baby is born. [dermcoll.edu.au]

  These are called excoriations and may be complicated with bacterial infections as well. The itching sites may sometimes bleed due to excessive scratching. Due to chronic itching the nails of the patient may also appear shiny and smooth. [news-medical.net]

  Pruritus usually affects the palms and soles but may extend to the legs and abdomen or become generalized.4 Generally, there are no cutaneous signs other than excoriation marks, contrary to primary skin lesions found in other specific dermatoses of pregnancy [mdedge.com]

  • The pruritus worsens with the onset of jaundice, and the patient's skin can become excoriated. • The symptoms usually abate within 2 days after delivery. 11. [slideshare.net]

• Confusion

  On examination, patients may have pyrexia (in 90% of cases), rigors, jaundice, right upper quadrant tenderness, confusion, hypotension, and tachycardia may be present. [teachmesurgery.com]

  Introduction[1] Acute obstructive cholangitis was defined by Reynolds and Dargan in 1959 as a syndrome consisting of lethargy or mental confusion and shock, as well as fever, jaundice, and abdominal pain caused by biliary obstruction. [patient.info]

  Poor prognostic factors Various factors from literature to suggest poor prognosis 10,12,13,14 high fever >39°C shock organ dysfunction advanced age >75 years mental confusion malignancy as etiology medical comorbidities hyperbilirubinemia ≥2.2 mg/dL reduced [radiopaedia.org]

  Symptoms of liver encephalopathy include confusion, impaired consciousness, changes in cognitive function (thinking, decision-making, memory), mood changes, impaired judgment, disorientation, sluggish speech and movement, drowsiness and coma. [livestrong.com]

  Confusion can indicate sepsis and could be the only presenting feature in the very elderly. Hypotension/shock can be seen in severe cases. Darkening of urine might be noticed by the patient or family members. [cancertherapyadvisor.com]

• Somnolence

  Newton JL, Gibson GJ, Tomlinson M, et al: Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence. Hepatology 2006;44:91–98. [clevelandclinicmeded.com]

• Dark Urine

  urine Inability to digest certain foods Itching Nausea or vomiting Pain in the right upper part of the abdomen Yellow skin or eyes Blood tests may show that you have elevated bilirubin and alkaline phosphatase. [medlineplus.gov]

  It can also be accompanied by: jaundice pale stools dark urine abdominal pain nausea See your doctor if you have itching in pregnancy. [healthline.com]

  The most common symptoms are: Overall itching, especially the palms of the hands and soles of the feet Mild nausea and pain in the upper right part of the belly Dark urine color Light coloring of stools (bowel movements) Easy bleeding Chills Pain from [choc.org]

  Dark urine[citation needed] Causes[edit] Possible causes: pregnancy androgens birth control pills antibiotics (such as TMP/SMX) abdominal mass (e.g. cancer) biliary atresia and other pediatric liver diseases biliary trauma congenital anomalies of the [en.wikipedia.org]

• Renal Insufficiency

  The pathology of jaundice-related renal insufficiency: Cholemic nephrosis revisited. J Nephrol. 2006;19(2):229–33. PubMed Beuers U, Kremer AE, Bolier R, and Elferink RP. Pruritus in cholestasis: Facts and fiction. Hepatology. 2014;60:399–407. [acgcasereports.gi.org]

  Renal Insufficiency. Will require appropriate dose changes of various antibiotics. Acute renal failure is associated with a poorer prognosis. B. Liver Insufficiency. Patients do fairly well following endoscopic sphincterotomy via ERCP. [cancertherapyadvisor.com]

• Kidney Failure

  The patient had no confounding cause of kidney failure, and complete kidney recovery followed removal of the bile duct obstruction. [ncbi.nlm.nih.gov]

  The sheer size of my feet, ankles, calves, and all the way up past my knees due to pregnancy water retention capped off with IV fluids from my birth had me convinced I was in kidney failure. I nearly checked myself into the ER. [rookiemoms.com]

• Blood analysis: Elevated serum bilirubin levels, total serum bile salt concentration levels and total serum cholesterol level are found. Serum lipoprotein-X levels are elevated in conditions leading to obstructive cholestasis. Increased levels of of serum alkaline phosphatase, serum 5'-nucleotidase, and serum gamma-glutamyl transferase (GGT) are observed. Hematology screen may show anemia in case of malignancy. Leukocytosis is present in case of infection. Cholestasis often leads to abnormally shaped cells. In case of prehepatic jaundice, reticulocytosis may be seen and prothrombin time should be checked.
• Abdominal ultrasound and CT: Anatomic causes of obstructive cholestasis can be detected with ultrasonography and CT scan of liver and bile ducts. 
• Hepatoiminodiacetic acid [HIDA] scanning is used to identify anatomic causes of obstructive cholestasis and to differentiate between hepatocellular and obstructive cholestasis. 
• Endoscopic retrograde cholangiography or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography are useful to identify anatomic causes of obstructive cholestasis. Operative cholangiography, when done is definitive in detecting the cause. 
• Liver biopsy when possible, can lead to definitive diagnosis. 
• Urea, electrolytes and creatinine derangement signifies acute renal damage may be present. 

• Hypertriglyceridemia

  Abstract We present a 6-week-old male infant with persistent hyperbilirubinemia, hypertriglyceridemia, elevated creatine kinase levels, and transaminitis since the second week of life. [pediatrics.aappublications.org]

  […] asymptomatic primary biliary cirrhosis 硬化性胆管炎 sclerosing cholangitis 膠原病 collagen disease 甲状腺機能亢進症 hyperthyroidism 甲状腺機能低下症 hypothyroidism 甲状腺中毒症 thyrotoxicosis 後天性免疫不全症候群 acquired immune deficiency syndrome 高コレステロール血症 hypercholesterolemia 高トリグリセリド血症 hypertriglyceridemia [jsge.or.jp]

Medical therapy is largely ineffective in cholestasis. However, ursodeoxycholic acid (20-30 mg/kg/d) has been used in children to increase bile formation and antagonize the effect of hydrophobic bile acids on biological membranes. Children with chronic cholestasis may be given phenobarbital (5 mg/kg/d). Dietary substitution for treatment of fat malabsorption is recommended. Vitamin supplementation in chronic cholestasis, oral absorbable, fat-soluble vitamin formulation A, D, E, and K are given to children. Osteopenia, if present, is treated with bisphosphonates. Pruritus is treated with phototherapy, ursodeoxycholic acid, colestyramine, rifampicin and external biliary drainage. Surgical treatment is indicated for underlying causes that are amenable to surgery [9] [10].

Cholestasis can give rise to secondary liver disease like hepatic fibrosis, metabolic bone disease like osteopenia and osteoporosis, and life threatening bleeding tendencies in children. Prognosis depends on the underlying condition giving rise to cholestasis. Although cholestasis itself does not result in death, it causes significant morbidity due to the widespread systemic effects.

Cholestasis is classified as acute or chronic, and based on the localization of the interference of bile flow or formation, as extrahepatic (obstructive) and intrahepatic (hepatocellular) cholestasis.

Acute extrahepatic cholestasis is caused by obstruction to the bile ducts due to malignancy, benign bile duct stricture, bile duct compression, bile duct stones, gallstones and infectious cholangitis.

Drugs, viral infections, sepsis and cholestatic conditions can lead to acute intrahepatic cholestasis. Acute cholestasis may also occur as a part of paraneoplastic syndrome due to the release of inflammatory mediators from cancer cells. Other obstructive causes are Alagille syndrome and nonsyndromic ductal paucity.

Primary biliary cirrhosis and primary sclerosing cholangitis are considered causes of chronic cholestasis. Some other causes of hepatocellular cholestasis are drug-induced, alpha-1-antitrypsin deficiency, inborn errors of bile acid synthesis and cholestasis associated with total parenteral nutrition. Drugs that can cause cholestasis are antibiotics, contraceptive pills, anabolic steroids, cimetidine, chlorpromazine, imipramine, prochlorperazine, terbinafine, and tolbutamide. Intrahepatic cholestasis of pregnancy is reversible, influenced by hormones and develops in late pregnancy in women with genetic predisposition [2] [3] [4].

More than 70% of all cholestasis cases have extrahepatic causes. Although there is not differences between men and women in the incidence of cholestasis induced by genetic diseases, overall women are more affected due to cholestasis in pregnancy. Biliary atresia and drug-induced cholestasis also occur more in women. Pediatric cholestasis is also more common as newborns and infants have an immature liver [5] [6].

In hepatocellular cholestasis bile is present within hepatocytes and canalicular spaces leading to hepatocellular injury. Bile plugging of the interlobular bile ducts, bile duct proliferation in association with centrilobular cholate injury and portal expansion is found in obstructive cholestasis.

There is increased cholesterol content of membranes leading to imapirment of the functioning of integral membrane proteins. Retention of bile salts results in injury to biological membranes throughout the body, with most damage to the liver. Bile salts may be a mediator of hepatic fibrosis as well. Injury to red blood cells can result in spur-cell hemolytic anemia [7].

There is no definitive way to prevent cholestasis, but timely diagnosis and treatment can prevent debilitating and serious complications. The possibility of cholestasis should be borne in mind in patients undergoing total parenteral nutrition, or who are pregnant or have any of the known associated genetic conditions. Vaccination against viral hepatitis can prevent the related cases of cholestasis.

As the bile flow from the gallbladder into the duodenum is hindered, cholestasis leads to retention of bile and regurgitation of unconjugated bilirubin and bile salts into the serum, leading to major effects on all organ systems. Jaundice, pruritus, nausea, vomiting, and pain are frequent symptoms. Management consists of treatment of underlying cause and treatment of pruritus [1].

• Definition: Cholestasis is the term used when the flow of bile from the gall bladder into the small intestine is slowed or blocked.
• Cause: The liver related causes can be infections, pregnancy, alcoholic liver disease, cancers, and primary biliary cirrhosis. The causes that are outside liver are commonly bile duct tumors, stones, pancreatic diseases, and cysts. 
• Symptoms: The white of your eyes may look yellowish. There may be yellow tinge to the skin and dark colored urine. Commonly the stool may be clay colored or white and you may have digestion problems. There can be nausea and vomiting and pain in the upper part of the abdomen. You may have itching. 
• Diagnosis: Some blood tests will be done to see the level of contents of bile in the blood and other enzymes that show the functioning of the liver. Ultrasound and CT scan of the abdomen may be done. A test called endoscopic retrograde cholangiopancreatography (ERCP) may be useful. 
• Treatment and follow-up: Treatment involves treating the cause of the bile flow obstruction like removal of stones and treatment of infection. Although completely resolved bile duct stones and such acute problems may not cause require frequent follow-ups, you must continue regular follow up for chronic diseases according to your physician’s recommendation, and consult a doctor for any recurrence of symptoms. 

1. Sellinger M, Boyer JL. Physiology of bile secretion and cholestasis. Prog Liver Dis. 1990;9:237-59.
2. Karlsen TH, Vesterhus M, Boberg KM. Review article: controversies in the management of primary biliary cirrhosis and primary sclerosing cholangitis. Aliment Pharmacol Ther. 2014;39(3):282-301.
3. Kimmings AN, Van deventer SJ, Obertop H, Rauws EA, Gouma DJ. Inflammatory and immunologic effects of obstructive jaundice: pathogenesis and treatment. J Am Coll Surg. 1995;181(6):567-81.
4. Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2014;124(1):120-33.
5. James OF, Myszor M. Epidemiology and genetics of primary biliary cirrhosis. Prog Liver Dis. 1990;9:523-36.
6. Mathias A, Wax JR, Pinette MG, Cartin A, Blackstone J. Progressive familial intrahepatic cholestasis complicating pregnancy. J Matern Fetal Neonatal Med. Jun 1 2009;1-3.
7. Elferink RP, Groen AK. The mechanism of biliary lipid secretion and its defects. Gastroenterol Clin North Am. Mar 1999; 28(1):59-74, vi.
8. Gossard AA, Talwalkar JA. Cholestatic liver disease. Med Clin North Am. 2014; 98(1):73-85.
9. Beuers U, Kremer AE, Bolier R, Elferink RP. Pruritus in cholestasis: facts and fiction. Hepatology. 2014;60(1):399-407.
10. Festi D, Montagnani M, Azzaroli F, et al. Clinical efficacy and effectiveness of ursodeoxycholic acid in cholestatic liver diseases. Curr Clin Pharmacol. May 2007; 2(2):155-77.