Case studies – Jaundice

Case study-1

A 24 –year –old male suffering from Malaria was put on Primaquine. He developed malaise, fatigue and yellow discoloration of sclera and skin.

On examination – There was pallor- ++, icterus ++, Pulse – 100/min., Temperature 102°F. The liver and spleen were palpable.

The investigation report was as follows-

Hb-5gm%

TLC-13000 cmm esp. polymorphs

Serum bilirubin- 6 mg%

Van den Bergh- Indirect positive.

Urine- Hemoglobin + and  Urobilinogen +

The color of the urine was brownish black

What is the probable diagnosis?

What is the relationship between primaquine intake and the present manifestations?

Case Details- This is a case of primaquine induced Hemolytic anemia, progressing to jaundice. Glucose-6-P dehydrogenase deficiency seems to be the underlying defect. High fever is due to malaria, while pallor and icterus are due to hemolytic anemia and underlying jaundice as apparent from low Hb and high bilirubin levels. Indirect positive Van Den Bergh indicates Uncinjugated Bilirubinemia. Urine is positive for hemoglobin and urobilinogen indicating the underlying hemoglobinuria and hemolytic jaundice

Primaquine being an oxidant drug precipitates the underlying defect to induce hemolysis. (See the details below).The liver has the capacity to conjugate and excrete over 3000 mg of bilirubin per day, whereas the normal production of bilirubin is only 300mg/day. The excess capacity allows the liver to respond to increased haem degradation with a corresponding increase in conjugation and secretion of bilirubin diglucuronide. 

However massive lysis of red blood cells, as in Glucose-6 –phosphate dehydrogenase deficiency, may produce bilirubin faster than it can be conjugated. More bilirubin is excreted into the bile, the amount of urobilinogen entering the enterohepatic circulation is increased and urinary urobilinogen is also increased. Unconjugated bilirubin levels become elevated in the blood causing jaundice.

A 10 –year- old boy received a sulfonamide antibiotic as prophylaxis for recurrent urinary tract infections. Although he was previously healthy and well-nourished, he became progressively ill and presented with pallor and irritability. A blood count revealed that he was severely anemic with jaundice due to hemolysis of the red blood cells.

What is the problem with the boy?

What is the cause of anemia and jaundice in this boy?

What is the simplest way for the diagnosis of this problem?

Case details The child is suffering from Glucose-6-phosphate dehydrogenase deficiency. The individuals with G-6-P-D deficiency present with excessive hemolysis on exposure to certain drugs like antibiotics, analgesics, and Antimalarials. Acute HA can develop as a result of three types of triggers: (1) fava beans, (2) infections, and (3) drugs. Glucose 6-phosphate dehydrogenase (G6PD) is an enzyme critical in the redox metabolism of all aerobic cells. In red cells, its role is even more critical because it is the only source of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which, directly and via reduced glutathione (GSH), defends these cells against oxidative stress.

NADPH is a required cofactor in many biosynthetic reactions which also maintains glutathione in its reduced form. Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the cell. With the help of the enzyme glutathione peroxidase, reduced glutathione converts harmful hydrogen peroxide to water. The inability to decompose hydrogen peroxide results in free radical-induced membrane disruption and reduced life span as a result of hemoglobin formation.G6PD deficiency is a prime example of hemolytic anemia due to interaction between an intracorpuscular and an extracorpuscular cause because in the majority of cases hemolysis is triggered by an exogenous agent. People deficient in glucose-6-phosphate dehydrogenase (G6PD) are not prescribed oxidative drugs, because their red blood cells undergo rapid hemolysis under this stress. Although in G6PD-deficient subjects there is a decrease in G6PD activity in most tissues, this is less marked than in red cells, and it does not seem to produce symptoms.

Clinical manifestations The vast majority of people with G6PD deficiency remain clinically asymptomatic throughout their lifetime.

However, all of them have an increased risk of developing neonatal jaundice (NNJ) and the risk of developing acute HA when challenged by a number of oxidative agents. Typically, a hemolytic attack starts with malaise, weakness, and abdominal or lumbar pain. After an interval of several hours to 2–3 days, the patient develops jaundice and often dark urine, due to hemoglobinuria. The onset can be extremely abrupt, especially with favism in children. The anemia is moderate to extremely severe, usually normocytic and normochromic, and due partly to intravascular hemolysis; hence, it is associated with hemoglobinuria, hemoglobinuria, and low or absent plasma Haptoglobin. Jaundice is prehepatic.

The laboratory workup for glucose-6-phosphate dehydrogenase (G6PD) deficiency includes the following:

Treatment- Identification and discontinuation of the precipitating agent is critical in cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency. Affected individuals are treated with oxygen and bed rest, which may afford symptomatic relief. Prevention of drug-induced hemolysis is possible in most cases by choosing alternative drugs. When acute HA develops and once its cause is recognized, no specific treatment is needed in most cases. However, if the anemia is severe, it may be a medical emergency, especially in children, requiring immediate action, including blood transfusion. 

A 50 –year-old woman had an 8-day history of loss of appetite, nausea and flu-like symptoms. She had noticed that her urine had been dark in color over the past two days. On examination, she had tenderness in the right upper quadrant. 

Laboratory investigations showed;

Serum Total bilirubin 4.5 mg%

Direct bilirubin 2.5 mg%

Indirect bilirubin 2.0 mg%

Serum AST- 40 IU/L

Serum ALT-115 IU/L

Serum ALP- 20 Units (KA)

What is the probable diagnosis?

What will be the observation regarding bile pigments in urine?

Case details Flu-like symptoms are indicative of viral hepatitis. Damage to liver cells can cause unconjugated bilirubin to increase in the blood as a result of decreased conjugation. The bilirubin that is conjugated is not efficiently secreted into the bile, but instead diffuses into the blood. Urobilinogen is increased in urine because hepatic damage decreases the enterohepatic circulation of this compound allowing more to enter the blood, from which it is filtered into the urine. The urine thus becomes dark in color, whereas stools are pale-colored. Plasma levels of AST and ALT are elevated. This is a case of hepatic jaundice.

Case-4

Based on the following clinical laboratory data, give the most probable diagnosis

Serum bilirubin 4 mg%

Direct bilirubin 0.2 mg%

Serum Alkaline phosphatase 6 units( KA)

SGOT- 30 IU/L

SGPT- 26 IU/L

Urine Bilirubin- Negative

Urine urobilinogen-Positive

Urine Bile Salts- Negative

Case details- Normal enzyme profile, Hyperbilirubinemia, absence of urinary bilirubin and positive urobilinogen are indicative of Hemolytic jaundice.

 A 40 –year- old, fat female, presents with intolerance to fatty foods, pain in the right side of the abdomen, yellowing of eyes and passage of clay-colored stools.

Laboratory Investigations revealed

Serum

Total Bilirubin – 20 mg%

Direct Bilirubin- 16 mg%

ALP- 800 U(KA)

SGPT- 90 IU/L

Urine

Color- deep yellow

Bilirubin- ++

Urobilinogen- absent

Stools

Clay-colored

Stercobilnogen- absent

What is the likely diagnosis?

Which other enzymes are likely to increase?

Case details This is a case of obstructive jaundice due to gall stones. This patient fits the “classic” criteria of gallbladder disease: female, middle-aged, overweight. Gallstones are collections of solid material (predominantly crystals of cholesterol) in the gallbladder. Gallstones may cause pain. Pain develops when the stones pass from the gallbladder into the cystic duct, common bile duct, or ampulla of Vater and block the duct. Then the gallbladder dilates, causing pain called biliary colic. The pain is felt in the upper abdomen, usually on the right side. Eating a heavy meal can trigger biliary colic, but simply eating fatty foods does not.

In this instance, jaundice is not due caused due to the overproduction of bilirubin but instead results from obstruction of the bile duct from the gall stones. The liver regurgitates conjugated bilirubin into the blood (Hyperbilirubinemia)

High direct bilirubin (Conjugated hyperbilirubinemia), high alkaline phosphatase (a marker of cholestasis),slightly increased SGPT level is suggestive of post hepatic or obstructive jaundice. Furthermore, the diagnosis is supported by the presence of bilirubin (since it is conjugated) and the absence of urobilinogen (Since there is an obstruction to the outflow of bile) in the urine. Due to the same reason for obstruction stool is clay-colored as stercobilnogen is absent.

Treatment is based on relieving the obstruction surgically. Prolonged obstruction of the bile duct can lead to liver damage and a subsequent rise in unconjugated hyperbilirubinemia and a rise in SGPT levels.

Case Study- 6

An Rh-negative mother delivers a baby who develops jaundice immediately after birth.

 General Examination reveals

Heart Rate    80/min

Icterus          +

Irritability     +

Liver            Palpable

 Laboratory Investigations

Serum

Bilirubin

Alkaline phosphatase    50 U/L

Urine          

Urobilinogen           +++

Feces

Stercobilnogen        +++

What is your likely diagnosis?     

Case details  This is a case of hemolytic jaundice due to Rh incompatibility. Indirect hyper bilirubinemia (Unconjugated hyperbilirubinemia),  high urinary urobilinogen and fecal stercobilnogen are indicative of hemolytic jaundice. Typically bilirubin is absent in urine since unconjugated bilirubin being water-insoluble and albumin-bound (macromolecule), can not pass through glomeruli to appear in the urine.