2 - Jaundice Flashcards
What is jaundice?
Yellowing of the skin and sclera due to bilirubin deposition
Also called hyperbilirubinemia.
What are the two pathways of hemoglobin degradation?
Intravascular and extravascular degradation pathways
These pathways involve the breakdown of hemoglobin and the processing of bilirubin.
What is the normal serum bilirubin level?
1.0 mg/dL
A concentration must double or triple before jaundice becomes clinically visible.
What are the main causes of jaundice?
- Excess heme degradation
- Impaired bilirubin transport and uptake
- Disruption of bilirubin metabolism
- Obstruction of bile flow
What is cholestasis?
Any obstruction to bile flow
Can be classified as intrahepatic or extrahepatic.
How does hemolysis lead to jaundice?
Increased bilirubin production from the breakdown of red blood cells.
What are liver function enzymes used for?
To diagnose various types of jaundice.
What distinguishes alpha-thalassemia from beta-thalassemia?
Alpha-thalassemia involves deletions of alpha-globin genes; beta-thalassemia involves reduced synthesis of beta-globin genes.
What is the biochemical basis of hemochromatosis?
Excessive accumulation of iron in the body.
What are the functions of the liver and pancreas?
- Metabolism
- Detoxification
- Bile production (liver)
- Enzyme secretion (pancreas)
These functions are linked to symptoms of cirrhosis and pancreatic cancer.
What is neonatal hyperbilirubinemia?
Excess bilirubin in newborns requiring evaluation and treatment.
What is the van den Bergh reaction?
A colorimetric assay used to estimate serum bilirubin levels.
What is the significance of direct versus indirect bilirubin?
Direct bilirubin is water-soluble; indirect bilirubin is unconjugated.
What can cause intravascular hemolysis?
- Cardiac hemolysis from artificial heart valves
- Complement fixation
- Toxin exposure
- Thermal damage
What is the lifespan of red blood cells in thalassemia?
Shortened lifespan of 6.5 days compared to the normal 120 days.
What clinical findings are associated with beta-thalassemia?
- Jaundice
- Osteoporosis
- Growth retardation
- Pigmented gallstones
What is the role of haptoglobin in hemolysis?
Binds free hemoglobin to prevent kidney damage.
What is the typical presentation of a patient with thalassemia intermedia?
Worsening shortness of breath, jaundice, and chronic anemia.
What laboratory studies can clarify the diagnosis in thalassemia?
- Reticulocyte count
- Serum haptoglobin
- LDH level
What can a chest X-ray reveal in thalassemia patients?
Signs of fluid overload and possible heart enlargement.
What is a possible complication of splenectomy in thalassemia patients?
Increased risk of sepsis, especially by pneumococcus.
What is fetal hemoglobin (HbF) composed of?
Two alpha and two gamma chains.
What is a minor component of adult hemoglobin?
HbA2, which has two alpha and two delta chains.
How is thalassemia inherited?
In an autosomal recessive manner.
What are the two major types of thalassemia?
- Alpha-thalassemia
- Beta-thalassemia
What characterizes alpha-thalassemia?
Deletions of the alpha-globin genes.
What is the defining feature of beta-thalassemia?
Reduced synthesis of beta-globin genes.
What happens when one alpha chain gene is deleted in alpha-thalassemia?
It presents with a mild microcytic hypochromic defect in hemoglobin production.
What is hydrops fetalis?
Deletion of all four alpha-globin chains, incompatible with life.
What condition does beta-thalassemia result from?
Mutations affecting every step of gene expression for beta chain synthesis.
What are the prominent signs and symptoms of thalassemias?
Varying degrees of clinical disease manifestations.
What is the main cause of hemolytic anemia?
Premature removal of erythrocytes due to intrinsic or extrinsic factors.
What are the two pathways of red cell removal after hemolysis?
- Intravascularly
- Extravascularly in the reticuloendothelial system.
What characterizes extravascular hemolysis?
Removal of senescent red blood cells by macrophages.
What happens during intravascular hemolysis?
Red blood cells are lysed in the circulation.
What are schistocytes?
Fragments of normal erythrocyte membrane resulting from intravascular hemolysis.
What is the role of haptoglobin?
To bind free hemoglobin dimers and prevent their escape into the kidney.
What is the first product of hemoglobin metabolism?
Biliverdin, which is then converted to bilirubin.
How is bilirubin transported to the liver?
Bound to albumin.
What conversion occurs in the hepatocyte regarding bilirubin?
Bilirubin is conjugated with glucuronic acid.
What happens to conjugated bilirubin in the intestine?
It is hydrolyzed to unconjugated bilirubin by bacterial glucuronidases.
What is kernicterus?
Irreversible CNS damage in newborns due to high levels of unconjugated bilirubin.
What are the symptoms of kernicterus?
- Cerebral palsy-like movements
- Visual and hearing damage
- Intellectual disabilities.
What bilirubin level is considered hyperbilirubinemia?
Exceeding 1.0 mg/dL.
What bilirubin level indicates jaundice?
Exceeding 2.0 mg/dL.
What is the significance of bilirubin elevation lasting longer than 2 weeks?
It requires further evaluation for potential pathology.
What are some potential causes of jaundice in newborns?
- Biliary atresia
- Immune-mediated hemolysis
- Hereditary spherocytosis
- G6PD or pyruvate kinase deficiencies.
What is the consequence of untreated acute bilirubin encephalopathy?
Permanent neurologic damage (kernicterus).
What is the relationship between ineffective erythropoiesis and hemolytic anemia?
Ineffective erythropoiesis can cause hemolytic anemia and unconjugated hyperbilirubinemia.
What characterizes extravascular hemolysis?
Chronic phenomenon with elevated reticulocyte count and unconjugated bilirubin.
What is the metabolic pathway of hemoglobin degradation?
Hemoglobin -> Biliverdin -> Bilirubin -> Conjugation in the liver.
True or False: Jaundice in the first 24 hours of life is physiologic.
False.
What is biliary atresia?
A condition to consider when jaundice is not physiologic in nature.
What causes immune-mediated hemolysis in neonates?
ABO or Rh incompatibility.
What are hereditary conditions associated with jaundice?
Hereditary spherocytosis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiencies.
What is a cephalohematoma?
A type of closed space hematoma that can cause jaundice.
What can prolong physiologic jaundice in neonates?
Breast milk may prolong jaundice beyond the 2-week period.
What is the main biochemical basis of neonatal jaundice?
Accumulation of indirect bilirubin in plasma.
What is physiologic jaundice in the neonate?
Jaundice due to increased bilirubin load, decreased conjugation, and impaired excretion.
How does bilirubin accumulate in neonates?
Due to shorter half-life of red blood cells and low hepatic enzyme activity.
What is the role of albumin in bilirubin metabolism in infants?
Infants have lower albumin levels, allowing more unbound bilirubin to circulate.
What is the neurotoxic effect of unconjugated bilirubin?
It can accumulate in the basal ganglia, causing acute bilirubin encephalopathy.
What is breastfeeding jaundice?
Jaundice due to delayed milk production or decreased milk intake leading to dehydration.
What is breast milk jaundice?
Jaundice that occurs after the first week of life due to factors in breast milk.
What indicates pathologic jaundice in a neonate?
Jaundice occurring within the first 24 hours of life.
What is the standard treatment for jaundice in neonates?
Phototherapy.
What wavelength of light is most effective in phototherapy?
425-475 nm.
What is the expected bilirubin range in normal physiologic jaundice?
10 to 20 mg/dL.
What are the subnormal enzyme levels in neonates that affect bilirubin metabolism?
GST-beta, glutathione S-transferase, and UDP-GT levels.
What factors exacerbate breastfeeding jaundice?
Poor oral intake, inadequate caloric content, and dehydration.
What is Gilbert syndrome?
A benign condition characterized by slightly elevated indirect bilirubin levels.
What is the most common inherited disorder of bilirubin metabolism?
Gilbert syndrome.
How is Gilbert syndrome inherited?
Autosomal recessive pattern.
What differentiates Gilbert syndrome from Crigler-Najjar syndrome?
Crigler-Najjar syndrome has reduced or absent UGT1A1 activity, leading to severe jaundice.
What are the two syndromes that cause accumulation of direct bilirubin?
Dubin-Johnson syndrome and Rotor syndrome.
What genetic mutation causes Dubin-Johnson syndrome?
Mutations in the MRP2 gene.
What is Rotor syndrome characterized by?
Intermittent jaundice with predominantly conjugated bilirubin.
What is the clinical significance of conjugated bilirubin?
It is eliminated in bile and can cause dark pigmentation in the liver.
What is the typical bilirubin level in Gilbert syndrome?
Slightly elevated unconjugated bilirubin.
What is kernicterus?
A serious complication of untreated hyperbilirubinemia in neonates.
What proteins are expressed on the sinusoidal membrane of hepatocytes responsible for?
They are responsible for the uptake of bilirubin by the liver
These proteins also transport bile acids, conjugated steroids, eicosanoids, thyroid hormones, and cholecystokinin.
What syndrome clinically resembles Dubin-Johnson syndrome?
Rotor syndrome
What does an isolated elevation of bilirubin in a healthy adolescent suggest?
It may suggest a congenital hyperbilirubinemia.
What is the most common cause of congenital hyperbilirubinemia?
Gilbert syndrome
What genetic defect leads to Gilbert syndrome?
A defect in the transcription promoter region of the UGT1A1 gene
What does Gilbert syndrome cause in terms of bilirubin levels?
It leads to a low expression of UDP-glucuronyltransferase and thus an elevation of unconjugated bilirubin.
What are benign hyperbilirubinemias typically characterized by?
They are usually asymptomatic with very mild jaundice.
What can precipitate the mild jaundice seen in benign hyperbilirubinemias?
Intercurrent infection or fasting.
What must be included in the differential diagnosis if the elevation in bilirubin is predominantly unconjugated?
Hemolysis
What memory tool can be used for clinical decision making in congenital hyperbilirubinemia disorders?
Dubin-Johnson presents with primarily elevated direct bilirubin, while Gilbert is primarily indirect.
What symptoms did the 55-year-old man present with?
Yellowing of the eyes, generalized weakness, weight gain, increased abdominal girth
What is the edema rating scale used for?
To grade the degree of pitting edema from +1 to +4.
What does portal hypertension indicate?
Inhibition of blood flow through the liver due to cirrhosis
What is a spider angiomata?
A vascular malformation on the skin commonly seen in chronic liver disease.
What does the presence of spider angiomata suggest?
It suggests liver disease.
What laboratory studies might clarify a diagnosis of liver disease?
Complete blood count (CBC), metabolic profile, prothrombin time, imaging study of the hepatobiliary system
What does the laboratory pattern for liver function tests in chronic liver disease typically show?
A cholestatic picture with elevated bilirubin and alkaline phosphatase.
What does a CT scan reveal in cases of chronic liver disease?
A dense, nonhomogeneous liver, moderately enlarged spleen, and small amount of ascitic fluid.
What does a negative result for hepatitis B and C indicate?
It helps exclude primary biliary cirrhosis and autoimmune hepatitis.
What is Wilson disease characterized by?
Defect in copper transport resulting in deposition of toxic amounts of copper.
What finding is pathognomonic for Wilson disease?
Kayser Fleischer ring
What supports hemochromatosis as a working diagnosis?
90% transferrin saturation and markedly elevated ferritin.
What are the pathologic consequences of hemochromatosis?
Iron deposition in tissues such as skin, heart, and pancreas.
What is the central feature of cirrhosis?
Progressive death of hepatocytes and collagen deposition.
What activates stellate and Kupffer cells in cirrhosis?
Pathologic stimuli such as toxic substances, drugs, and chronic inflammation.
What is the result of fibrotic changes in cirrhosis?
Increased vascular resistance and portal hypertension.
What causes jaundice in end-stage cirrhosis?
Disruption of the bile ductular system.
What is the main cause of encephalopathic changes in liver disease?
Reduced detoxification of ammonia in the urea cycle.
What is the genetic implication of hemochromatosis?
It is an autosomal recessive disorder.
What is the role of hepcidin in iron homeostasis?
Hepcidin is a hormone secreted by the liver that regulates iron levels in circulation by binding to ferroportin, inhibiting dietary absorption and release of iron from macrophages and hepatocytes.
What is the primary function of transferrin in the body?
Transferrin is the main protein involved in iron transport in plasma, distributing iron mainly to the liver, muscle, and bone marrow.
What are the clinical manifestations of cirrhosis when liver damage reaches 80% or greater?
- Encephalopathy
- Clotting disorders
- Portal hypertension
- Feminization in males
- Malnutrition
- Fluid overload
What is the significance of ferritin in iron storage?
Ferritin is the major protein used for intracellular storage of iron and can bind to approximately 4500 iron atoms.
What happens to iron levels when hepcidin synthesis increases?
Increased hepcidin synthesis limits iron absorption from the gut and release from iron stores.
What is the most prevalent genetic disorder causing iron overload in Caucasians?
Hereditary hemochromatosis (HH) caused by mutations in the HFE gene.
What is the treatment of choice for hemochromatosis?
Periodic venesection (phlebotomy) to halt further deposition of iron and resultant tissue damage.
What could low serum albumin and a lengthening prothrombin time indicate?
They are indicators of failing hepatic synthetic function and probable cirrhosis.
What is choledocholithiasis?
A stone lodged in the biliary tree, which may be present with gallstones or reform after cholecystectomy.
What is the definition of cholestasis?
Any obstruction to bile flow.
What are the possible etiologies of cirrhosis considered in the case study?
- Alcohol abuse
- Chronic hepatitis (B or C)
- Hemochromatosis
- Nonalcoholic steatohepatitis (NASH)
What imaging study was performed to investigate the patient’s condition?
A CT scan of the abdomen with oral contrast.
What did the CT scan reveal about the patient’s pancreas?
A 4 cm mass in the head of the pancreas.
How does iron overload occur in hereditary hemochromatosis?
Low hepcidin levels lead to increased ferroportin activity, resulting in increased dietary iron uptake and iron release from macrophages.
What is the relationship between free iron and cellular toxicity?
Free iron in the circulation can be toxic to cells; hence, it is stored in the form of ferritin or hemosiderin.
What is the primary role of iron regulatory proteins (IRPs)?
IRPs regulate iron availability at the cellular level, controlling transferrin and ferritin levels.
What can chronic hemochromatosis cause in terms of skin and organ damage?
It may cause bronzed pigmentation of the skin and damage to liver and pancreatic tissue, potentially leading to diabetes mellitus.
What is the significance of the porta hepatis?
It is the area central to the liver where the hepatic ducts meet and is often a site for metastatic malignancy.
What laboratory tests would be appropriate for diagnosing liver disease in this case?
- Complete blood count (CBC)
- Liver function tests
- Total protein and albumin levels
- Prothrombin time (INR)
- Gene analysis for HFE
- Viral serologies for hepatitis B and C
What does the term ‘sphincterotomy’ refer to?
A procedure to widen or enlarge the opening in any sphincter, such as the sphincter of Oddi.
What is the condition characterized by a firm enlarged liver and metabolic function holding despite alcohol abuse?
Cirrhosis
Cirrhosis is often associated with chronic liver disease and can be a result of chronic alcoholism.
What imaging study was requested to investigate the patient’s condition?
CT scan of the abdomen with oral contrast
This imaging helps to identify masses and structural changes in the abdominal organs.
What did the CT scan reveal in the head of the pancreas?
A 4 cm mass
This mass is likely malignant, contributing to the patient’s symptoms.
What is the significance of the dilated common bile duct observed in the CT scan?
It indicates obstruction
A dilated common bile duct can be a sign of obstructive jaundice due to a mass in the pancreas.
What suggests the presence of metastatic disease in the liver?
Two 3-cm nodules in the left lobe
Metastatic disease often presents as nodules in the liver, indicating spread from a primary malignancy.
What are the symptoms associated with the lesion in the head of the pancreas?
Cholestatic jaundice, pruritus, and weight loss
These symptoms are often indicative of biliary obstruction.
What happens to conjugated bilirubin once it is exported out by MRP2 into the bile duct?
It is secreted into the bile duct as part of the bile
This process is crucial for bile formation and digestion.
What is the molecular basis of obstructive jaundice?
Obstruction of the biliary tract
This can be caused by gallstones, stricture, or malignancy, leading to accumulation of bilirubin.
What toxic substances accumulate in the liver due to bile duct obstruction?
Bile salts and conjugated bilirubin
These substances can damage hepatocytes and lead to elevated liver function tests.
What does an absence of bile in the duodenum cause in stool color?
Clay-colored fecal material
This is due to lack of bilirubin breakdown products in the intestines.
What is the pattern of liver function tests in extrahepatic biliary obstruction?
Disproportionate elevation of bilirubin and alkaline phosphatase
This pattern is indicative of cholestasis.
What is the most common cause of extrahepatic biliary obstruction?
Mechanical obstruction
This is usually due to gallstones, tumors, or strictures.
What is a common symptom associated with obstructive jaundice?
Pruritus
It is linked to the accumulation of bile salts in the bloodstream.
What clinical findings suggest biliary tract obstruction?
Bile-colored urine and clay-colored stool
These findings indicate a lack of bilirubin reaching the intestines.
What is urobilinogen?
Metabolic product of bacterial degradation of bile salts
It is normally produced in the intestines and is important for stool color.
What are the main components of bile?
- Conjugated bilirubin
- Bile salts
- Lecithin
- Cholesterol
- Electrolytes
Bile is essential for fat digestion and absorption.
What does painless jaundice in an older individual suggest?
Pancreatic cancer until proven otherwise
Painless jaundice is a classic sign of malignancy in the pancreas.
What is the likely defect in a patient with elevated bilirubin and normal AST/ALT?
Multidrug resistance protein 2 (MRP2)
This defect leads to conjugated hyperbilirubinemia due to impaired transport.
What is the appropriate management step for a markedly jaundiced 2-day-old neonate?
Consult a pediatric surgeon and a geneticist
Rapid diagnosis is crucial to rule out serious conditions like biliary atresia.
What is the most likely explanation for jaundice in a patient with sickle cell anemia?
Biliary tract obstruction by pigment stones
Chronic hemolysis can lead to the formation of pigment stones that obstruct bile flow.
What is the expected change in urine urobilinogen concentration during hemolysis?
Decreased urine urobilinogen concentration
Hemolysis leads to increased indirect bilirubin but decreased conversion to urobilinogen.
What laboratory test is most appropriate to assess liver synthetic function?
Albumin
Albumin levels reflect the liver’s ability to synthesize proteins.
What pattern of liver function tests would suggest a viral hepatitis infection?
Elevated AST/ALT with normal alkaline phosphatase
This pattern indicates hepatocellular injury rather than cholestasis.
What is the most likely finding in a patient with hemochromatosis?
Decreased hepcidin
Low hepcidin levels lead to increased iron absorption and overload.
What is the most appropriate next step for a breast-fed newborn with jaundice?
Continue breastfeeding
In most cases, breastfeeding should be continued unless there is a specific contraindication.
What is a common finding in the urine of a patient with obstructive jaundice?
Dark yellow urine
This is due to the overflow of conjugated bilirubin into the urine.
What does a 74% saturation of iron-binding protein with highly elevated ferritin levels indicate?
Iron overload
The most likely diagnosis is hemochromatosis.
What is hemochromatosis characterized by?
Unregulated iron absorption due to low levels of hepcidin.
What does low levels of hepcidin signal?
Increased ferroportin activity and increased iron uptake from the diet.
What is the role of UDP-GT in the liver?
Conjugates bilirubin with two glucuronyl units in hepatocytes.
What happens when iron concentrations become abnormally high in the liver?
The liver converts ferritin into hemosiderin.
What is the most likely diagnosis for a young woman presenting with symptoms of acute infectious illness and clinical jaundice after entering a highly endemic area?
Hepatitis A.
What does a 20-fold elevation of transaminases along with a bilirubin level of 10 suggest?
Marked hepatocellular damage and intrahepatic cholestasis.
What does a bilirubin level not exceeding 2.0 indicate?
The patient does not exhibit clinical jaundice.
What is a common clinical pattern for chronic inflammatory processes damaging hepatocytes?
Elevation of transaminases with other values within normal limits.
What does low albumin suggest in a patient with liver disease?
Significant loss of hepatocytes to synthesize proteins.
What is the most likely diagnosis if there is increased copper deposition in the cornea?
Wilson disease.
What is the classic triad of symptoms for Wilson disease?
Liver disease, hemolytic anemia, and neurologic findings.
What type of jaundice may develop in a healthy newborn after birth?
Physiologic, breastfeeding, and breast milk jaundice.
What usually causes breastfeeding jaundice in newborns?
Difficulty in breastfeeding or delayed milk production leading to dehydration.
What type of bilirubin is increased in obstructive jaundice due to a pancreatic tumor?
Direct (conjugated) bilirubin.
What happens to unconjugated (indirect) bilirubin in obstructive jaundice?
There should be no change.
What causes light-colored feces in obstructive jaundice?
Reduction in stercobilin due to obstruction of the biliary tract.
What is the expected bilirubin level in a patient with Gilbert syndrome?
Normal bilirubin levels.
What does an elevation of alkaline phosphatase indicate?
Inflammation/damage to the biliary ductal collecting system.
