Jaundice Flashcards
What’s jaundice?
Normal range of bilirubin
What level of jaundice is it clinical detectable
Definition:
Jaundice, also known as icterus, is a yellowish discoloration of the skin, sclera (the white part of the eyes), and mucous membranes. This occurs due to the accumulation of bilirubin in the bloodstream.
Normal Bilirubin Levels:
- Total Bilirubin Range: 3.4 to 20.0 micromol/L (0.2 to 1.2 mg/dL).
- Clinical Detection of Jaundice: Jaundice becomes noticeable when serum bilirubin levels exceed 51 micromol/L (3 mg/dL).
The causes of jaundice can be categorized into? With examples
Causes of Jaundice:
Jaundice can be broadly classified into three categories based on the underlying pathophysiology:
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Prehepatic (Hemolytic) Jaundice:
- Mechanism: Increased production of bilirubin, usually due to excessive breakdown of red blood cells (hemolysis).
- Examples: Hemolytic anemias, transfusion reactions, and sickle cell disease.
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Hepatocellular (Hepatic) Jaundice:
- Mechanism: Impairment in the ability of hepatocytes (liver cells) to process and excrete bilirubin.
- Examples: Viral hepatitis, alcoholic liver disease, cirrhosis, and drug-induced liver injury.
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Cholestatic (Post-hepatic) Jaundice:
- Mechanism: Obstruction of bile flow within the biliary system, leading to the accumulation of bilirubin.
- Examples: Gallstones, bile duct tumors, pancreatitis, and primary biliary cirrhosis.
How do you clinically evaluate jaundice? I. E history taking and physical examination
Diagnostic Evaluation:
To determine the cause of jaundice, a systematic approach involving history taking, physical examination, and specific investigations is essential:
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Focused History and Examination:
- History: Inquire about symptoms like dark urine, pale stools, pruritus (itching), abdominal pain, weight loss, and changes in appetite. Ask about alcohol use, medication history, travel history, and family history of liver diseases.
- Physical Examination: Look for signs like hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), ascites (fluid in the abdomen), and spider angiomas.
What are the investigations carried out in a jaundice patient
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Initial Investigations:
- Full Blood Count (FBC): To check for hemolysis or anemia.
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Serum Liver Function Tests (LFTs): To assess liver function. This includes:
- Serum Bilirubin (Total and Direct): Helps distinguish between conjugated (direct) and unconjugated (indirect) hyperbilirubinemia.
- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST): Elevated levels suggest hepatocellular damage.
- Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT): Elevated in cholestatic jaundice.
- Prothrombin Time (PT): May be prolonged in liver dysfunction.
- Ultrasound of the Liver and Biliary Tract: Non-invasive imaging to assess liver parenchyma and detect biliary obstruction.
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Further Investigations:
- Advanced Imaging: CT scan or MRI, especially if ultrasound suggests an obstruction or mass.
- Additional Laboratory Tests: Depending on the clinical context, tests like viral hepatitis serologies, autoimmune markers, and liver biopsy may be necessary.
Jaundice is a clinical sign of an underlying pathology, usually related to bilirubin metabolism or liver function. Early and appropriate evaluation, including history, physical examination, and targeted investigations, is essential to identify the cause and guide further management.
Explain the process of bilirubin metabolism
Bilirubin Production:
- Source: Bilirubin is a waste product that originates from the breakdown of the heme molecule found in red blood cells (RBCs).
- Process:
- RBCs have a lifespan of about 120 days. After this, they are broken down by macrophages in the reticuloendothelial system, primarily in the spleen, liver, and bone marrow.
- Heme Breakdown: The heme portion of hemoglobin is broken down into biliverdin and then reduced to form unconjugated bilirubin.
Unconjugated Bilirubin:
- Characteristics: This form of bilirubin is lipid-soluble, which allows it to easily cross cell membranes. However, it is not water-soluble, so it cannot be excreted directly.
- Transport in Blood: Unconjugated bilirubin is transported in the bloodstream bound to albumin, which helps prevent it from diffusing into tissues.
Hepatic Processing:
- Uptake: Hepatocytes (liver cells) take up unconjugated bilirubin from the blood.
- Conjugation: Within hepatocytes, unconjugated bilirubin is conjugated with glucuronic acid by the enzyme UDP-glucuronosyltransferase. This process converts unconjugated bilirubin into conjugated bilirubin, which is water-soluble and can be excreted from the body.
Excretion:
- Bile Secretion: Conjugated bilirubin is excreted into bile, which is then released into the intestines.
- Intestinal Processing:
- Conversion: In the intestines, gut bacteria convert conjugated bilirubin into urobilinogen and stercobilinogen.
- Excretion:
- Stercobilin: Most stercobilinogen is converted to stercobilin, which gives feces its brown color and is excreted in the stool.
- Urobilin: Some urobilinogen is reabsorbed into the blood, with a portion excreted by the kidneys as urobilin, which gives urine its yellow color.
Gilbert syndrome or Crigler-Najjar Syndrome causes what type of type of bilirubin elevation?
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Conditions like Gilbert’s syndrome or Crigler-Najjar syndrome involve genetic defects in the conjugation process, leading to elevated unconjugated bilirubin.
What are the types of bilirubin elevation and conditions that can cause them
Types of Bilirubin Elevation and Related Conditions:
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Increased Unconjugated (Indirect) Bilirubin:
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Causes:
- Prehepatic (Hemolytic) Jaundice: Increased red blood cell destruction leads to an excess of unconjugated bilirubin, overwhelming the liver’s capacity to conjugate it. This can occur in conditions like hemolytic anemia, sickle cell disease, or transfusion reactions.
- Impaired Conjugation: Conditions like Gilbert’s syndrome or Crigler-Najjar syndrome involve genetic defects in the conjugation process, leading to elevated unconjugated bilirubin.
- Clinical Implications: Since unconjugated bilirubin is lipid-soluble, it can cross the blood-brain barrier, particularly in newborns, leading to conditions like kernicterus.
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Causes:
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Increased Conjugated (Direct) Bilirubin:
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Causes:
- Hepatocellular Jaundice: When hepatocytes are damaged, as in hepatitis or cirrhosis, their ability to excrete conjugated bilirubin into the bile is impaired, leading to its buildup in the blood.
- Cholestatic (Obstructive) Jaundice: Obstruction in the bile ducts (e.g., due to gallstones, tumors, or strictures) prevents conjugated bilirubin from being excreted, causing it to back up into the bloodstream.
- Clinical Implications: Elevated conjugated bilirubin typically presents with dark urine (due to excreted urobilinogen) and pale stools (due to reduced stercobilin).
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Causes:
What are the classification of jaundice
1. Prehepatic Jaundice:
- Location of Dysfunction: Before the liver, typically due to increased bilirubin production.
- Bilirubin Type: Increased unconjugated (indirect) bilirubin.
- Causes: Hemolysis, ineffective erythropoiesis.
2. Hepatocellular Jaundice:
- Location of Dysfunction: Within the liver, due to impaired bilirubin conjugation or excretion.
- Bilirubin Type: Increased conjugated (direct) bilirubin, but unconjugated bilirubin can also be elevated if hepatocyte function is severely compromised.
- Causes: Hepatitis, cirrhosis, alcoholic liver disease.
3. Cholestatic (Obstructive) Jaundice:
- Location of Dysfunction: After the liver, in the biliary system, due to obstruction of bile flow.
- Bilirubin Type: Increased conjugated (direct) bilirubin.
- Causes: Gallstones, biliary atresia, pancreatic cancer.
What are the causes of preheparic jaundice
Overview:
Prehepatic jaundice is characterized by an increase in unconjugated (indirect) bilirubin in the bloodstream. This occurs either due to increased production of bilirubin from excessive red blood cell (RBC) destruction or due to a dysfunction in the liver’s ability to conjugate bilirubin. The underlying causes of prehepatic jaundice primarily involve conditions that affect RBCs or the initial stages of bilirubin metabolism.
When RBCs are destroyed at an accelerated rate, the amount of heme released from hemoglobin increases. This leads to a higher production of unconjugated bilirubin, which can overwhelm the liver’s ability to conjugate it, resulting in elevated levels of unconjugated bilirubin in the blood.
A. Hereditary Hemolytic Anemias:
- Hemoglobinopathies:
- Sickle Cell Anemia: A genetic disorder where abnormal hemoglobin (HbS) leads to the deformation of RBCs into a sickle shape, making them more prone to hemolysis.
- Thalassemia: A group of inherited disorders characterized by abnormal hemoglobin production, leading to the destruction of RBCs and ineffective erythropoiesis.
- Membranopathies:
- Hereditary Spherocytosis: A condition where RBCs have a defective cell membrane protein, making them spherical and prone to rupture.
- Elliptocytosis: Similar to spherocytosis but with elliptical-shaped RBCs, also leading to hemolysis.
- Pyropoikilocytosis: A severe form of hereditary elliptocytosis with marked RBC shape abnormalities and significant hemolysis.
- Enzymopathies:
- Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: A common enzymatic defect that renders RBCs vulnerable to oxidative stress, leading to hemolysis, particularly after exposure to certain drugs or infections.
- Pyruvate Kinase Deficiency: A metabolic disorder where the lack of pyruvate kinase enzyme causes energy depletion in RBCs, leading to their premature destruction.
B. Acquired Hemolytic Anemias:
- Autoimmune Hemolytic Anemia:
- Causes: Conditions like Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, and Scleroderma can cause the immune system to mistakenly attack RBCs, leading to their destruction.
- Infections:
- Malaria: A parasitic infection where the Plasmodium parasite invades RBCs, causing their rupture.
- Cytomegalovirus (CMV): A viral infection that can lead to hemolysis in some cases.
- Leishmaniasis: A parasitic disease that can cause hemolysis as part of its systemic effects.
- Infectious Mononucleosis: Caused by the Epstein-Barr virus, it can lead to mild hemolysis.
- Alloimmune Hemolytic Anemia:
- ABO Blood Group Incompatibility: Occurs when there is a mismatch in blood types between donor and recipient, leading to the immune-mediated destruction of transfused RBCs.
- Drug-Induced Hemolytic Anemia:
- Causes: Certain drugs can trigger hemolysis either through immune mechanisms or by directly damaging RBCs.
- Microangiopathic Hemolytic Anemias:
- Disseminated Intravascular Coagulation (DIC): A condition where widespread clotting in small vessels leads to RBC fragmentation (schistocytes) and hemolysis.
- Eclampsia: A severe complication of pregnancy characterized by hypertension and hemolysis, among other symptoms.
- Thrombotic Thrombocytopenic Purpura (TTP): A rare disorder where small blood clots form in blood vessels, leading to hemolysis and low platelet counts.
- Hemolytic Uremic Syndrome (HUS): Often triggered by infections (like E. coli), HUS leads to microangiopathic hemolysis, kidney failure, and low platelet counts.
In some cases, the liver’s ability to conjugate bilirubin is impaired, leading to an accumulation of unconjugated bilirubin in the blood. This can occur due to genetic defects affecting the enzymes responsible for bilirubin conjugation.
A. Gilbert Syndrome:
- Overview: Gilbert syndrome is a common, mild genetic disorder characterized by a reduced ability of the liver to conjugate bilirubin. This is due to a partial deficiency in the enzyme UDP-glucuronosyltransferase.
- Presentation: Patients may experience intermittent mild jaundice, often triggered by stress, fasting, or illness. The condition is typically benign and does not require treatment.
Prehepatic jaundice results from conditions that either increase the breakdown of RBCs (leading to excess unconjugated bilirubin production) or impair the liver’s ability to conjugate bilirubin. The causes range from hereditary disorders affecting hemoglobin, RBC membranes, or enzymes, to acquired conditions such as autoimmune diseases, infections, and drug reactions. Understanding the specific underlying cause is crucial for appropriate management and treatment of the jaundice.
Hepatocelluar case of jaundice causes the accumulation of what specific type of jaundice.
This results in the accumulation of both conjugated and unconjugated bilirubin in the blood
What are the infections that can cause hepatocelluar jaundice
Overview:
Hepatocellular jaundice arises when the liver’s hepatocytes (liver cells) are damaged or impaired, leading to a decrease in their ability to metabolize and excrete bilirubin. This results in the accumulation of both conjugated and unconjugated bilirubin in the blood. The underlying causes of hepatocellular jaundice can be diverse, including infections, toxins, malignancies, autoimmune disorders, genetic conditions, cardiac issues, and pregnancy-related complications.
A. Viral Infections:
- Hepatotrophic Viruses: These viruses specifically target the liver and are a common cause of liver inflammation (hepatitis) leading to jaundice.
- Hepatitis A, B, C, D, and E: These viruses cause varying degrees of liver damage, with Hepatitis B and C being notable for their potential to cause chronic liver disease and hepatocellular carcinoma.
- Non-Hepatotrophic Viruses: These are viruses that do not primarily target the liver but can cause liver damage as part of a systemic infection.
- HIV: While primarily an immune system virus, HIV can cause liver damage either directly or through co-infections (such as Hepatitis B or C) and the side effects of antiretroviral medications.
What are the parasites that can cause hepatocelluar jaundice
B. Parasitic Infections:
- Ascaris lumbricoides: This intestinal roundworm can migrate to the bile ducts, causing biliary obstruction and hepatocellular damage.
- Clonorchis sinensis (Chinese Liver Fluke): This parasite resides in the bile ducts, causing chronic inflammation, fibrosis, and an increased risk of cholangiocarcinoma.
- Echinococcus granulosus (Hydatid Disease): This tapeworm causes cysts in the liver, which can lead to jaundice if they rupture or cause obstruction.
- Entamoeba histolytica: The cause of amoebic liver abscesses, which can result in hepatocellular damage and jaundice.
- Malaria: The Plasmodium parasite, particularly P. falciparum, can cause severe liver damage leading to jaundice, often as part of a broader systemic illness.
What are the bacterial infections and toxins that causes hepatocelluar jaundice
C. Bacterial Infections:
- Leptospirosis: A bacterial infection that can cause Weil’s disease, characterized by severe jaundice, renal failure, and hemorrhage.
A. Alcohol:
- Chronic alcohol consumption can lead to a spectrum of liver diseases, including fatty liver, alcoholic hepatitis, and cirrhosis, all of which can impair hepatocyte function and cause jaundice.
What are the drugs that can cause B. Drug-Induced Liver Injury (DILI): leading to hepatocelluar J
B. Drug-Induced Liver Injury (DILI):
- Certain medications can cause hepatocellular damage, leading to jaundice. Common culprits include:
- Antibiotics: Some, like amoxicillin-clavulanate and isoniazid, are notorious for causing liver injury.
- Acetaminophen (Paracetamol): Overdose is a well-known cause of acute liver failure.
- Estrogen: Hormonal medications can cause cholestatic jaundice.
- Antiepileptics: Drugs like valproate and phenytoin can lead to hepatotoxicity.
- NSAIDs: Non-steroidal anti-inflammatory drugs, particularly diclofenac, can cause liver injury in susceptible individuals.
Malignancies and autoimmune dxs that can damage the liver function
A. Hepatocellular Carcinoma (HCC):
- This is the most common primary liver cancer, often arising in the context of chronic liver disease. It can cause jaundice either by direct hepatocyte damage or by obstructing the biliary tree.
B. Metastatic Liver Disease:
- Metastases to the liver from cancers elsewhere in the body (e.g., colon, breast, lung) can impair liver function, leading to jaundice.
C. Lymphoma:
- Both Hodgkin’s and non-Hodgkin’s lymphomas can infiltrate the liver, causing hepatocellular dysfunction and jaundice.
A. Autoimmune Hepatitis:
- A chronic inflammatory condition where the body’s immune system attacks hepatocytes, leading to progressive liver damage and jaundice.
B. Primary Biliary Cholangitis (PBC):
- A chronic disease where the immune system slowly destroys the bile ducts within the liver, leading to cholestasis, fibrosis, and cirrhosis.
C. Primary Sclerosing Cholangitis (PSC):
- A disease characterized by inflammation and scarring of the bile ducts, leading to liver damage and jaundice. PSC is often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis.
