Jaundice

Dr Mayank Agarwal
Assistant Professor
AIIMS, Raebareli
• What is the major metabolically available storage form of iron in the body?

a. Hemosiderin

b. Ferritin

c. Transferrin

d. Hemoglobin
• The total iron-binding capacity (TIBC) of the serum is an indirect measure of
which iron-related protein?

a. Hemosiderin

b. Ferritin

c. Transferrin

d. Haptoglobin
• The transfer of iron from the enterocyte into the plasma is REGULATED by:

a. Transferrin

b. Ferroportin

c. Ferritin

d. Hepcidin
• Following are several of many steps in process from absorption and transport of
iron to incorporation into heme. Place them in proper order.
i. Transferrin picks up ferric iron
ii. Iron is transferred to the mitochondria
iii. DMT1 transports ferrous iron into the enterocyte
iv. Ferroportin transports iron from enterocyte to plasma
v. The transferrin receptor transports iron into the cell

a. v, iv, i, ii, iii

b. iii, ii, iv, i, v
c. ii, i, v, iii, iv
d. iii, iv, i, v, ii
• The following is increased in iron deficiency anemia:

A. Serum iron

B. Serum ferritin

C. Total iron binding capacity

D. Ceruloplasmin
• A hematocrit is not recommended to screen for iron deficiency in children
because:

a. It is not sensitive enough to pick up anemia in children

b. Iron deficiency can be present without the presence of anemia

c. High levels of lead will affect the hematocrit accuracy

d. Serum ferritin is more cost effective

• In Iron deficiency anemia, the erythrocytic indices are typically

A. MCV increased, MCH decreased, and MCHC decreased

B. MCV decreased, MCH decreased, and MCHC decreased

C. MCV decreased, MCH increased, and MCHC decreased

D. MCV decreased, MCH decreased, and MCHC normal

• An increase in which one of the following suggests a shortened life span of
RBCs and hemolytic anemia?

a. Hemoglobin concentration

b. Hematocrit

c. Reticulocyte count

d. Red cell distribution width

• Anemia most commonly presents with which one of the following set of
symptoms:

a. Abdominal pain (from splenomegaly)

b. Shortness of breath and fatigue

c. Chills and fever

d. Jaundice and enlarged lymph nodes

• Which one of the following is reduced as an adaptation to long-standing
anemia?

a. Heart rate

b. Respiratory rate

c. Oxygen affinity of hemoglobin

d. Volume of blood ejected from the heart with each contraction

• Schistocytes, ovalocytes, and acanthocytes are examples of abnormal changes
in RBC:

a. Volume

b. Shape

c. Inclusions

d. Hemoglobin concentration
• The following is NOT a feature of microcytic hypochromic anemia:

A. Red blood cells smaller than normal

B. Central pallor less than normal 1/3rd

C. Reduced MCV and MCHC

D. It is due to decreased hemoglobin synthesis

• How would you classify the cell population with the following indices:

MCV 70 fL, MCH 25 pg, MCHC 33 g/dL?

a. Normocytic, normochromic

b. Macrocytic, normochromic

c. Microcytic, normochromic

d. Microcytic, hypochromic
• What are the initial laboratory tests that are performed for diagnosis of
anemia?

a. CBC, iron studies, and reticulocyte count

b. CBC, reticulocyte count, and peripheral blood film examination

c. Reticulocyte count and serum iron, vitamin B12, and folate assays

d. Bone marrow study, iron studies, and peripheral blood film examination
• Which one of the following conditions would be included in the differential
diagnosis of an anemic adult patient with an MCV of 125 fL and an RDW of
20% (reference interval 11.5% to 14.5%)?

a. Thalassemia

b. Sickle cell anemia

c. Iron deficiency

d. Vitamin B12 deficiency

• A 16-year-old boy from Shimla is found to have hemoglobin of 22 g/dL and
RBC count was found to be 8 millions/mm3. His physical examination and
other routine investigations are within normal limits.

1) Identify the condition. Secondary polycythemia

2) What is the cause? Hypoxia

3) Does he need treatment for this? No

• A 5-year-old child from a poor slum dweller family is brought to the doctor
with complaint of pica . On examination patient is having pallor, hemoglobin
concentration is 8 gm%.

1) What is the likely cause of anaemia? Iron deficiency

2) Enumerate other causes of anaemia.

• An investigator is studying the changes that occur in the oxygen-hemoglobin
dissociation curve of different types of hemoglobin under various conditions. The
blood obtained from a male infant shows decreased affinity for 2,3-
biphoshphoglycerate. Which of the following is most likely composition of the
hemoglobin molecule in this sample?
• A patient presents with hemoglobin of 7.9 g/dl, hematocrit of 23%, and mean
corpuscular volume of 89 fL. Erythropoietin level is quite low. What is the
most likely diagnosis?

A) Sickle cell anemia

B) Pernicious anemia

C) End-stage renal disease

D) Chronic blood loss

• A patient has a hematocrit of 63% and a reduced erythropoietin level. Based
on this information alone, what is the most likely diagnosis?

A) Prolonged and continued exposure to high altitude

B) Polycythemia vera

C) Chronic obstructive pulmonary disease with hypoxemia

D) Chronic kidney disease

• A 12-year-old African boy comes to the emergency department 3 hours after
the onset of severe back and chest pain. These problems started while he was
walking briskly through a hilly neighborhood. He has had similar episodes
numerous times in the past few weeks while performing physical activities.
Laboratory studies shows: Hemoglobin = 12 g/dl, Reticulocyte count = 7.0%.
What is this patient’s diagnosis?

A) Acute blood loss

B) Sickle cell anemia

C) Anemia of chronic disease

D) End-stage renal disease

• A 27-year-old female working 10-12 hours in corporate office found it difficult to
cope up with her daily activities, tiring very easily after a few hours of work. She
complained of excessive bleeding during menstruation. Her dietary habit
included lots of junk food. A quick hemoglobin estimation that revealed a
hemoglobin value of 8.5 g/dl. Her family doctor arrived at a provisional
diagnosis of anemia.

A. Name the most common cause of nutritional deficiency in India Fe deficiency

B. List the common signs and symptoms of anemia

C. Describe the most likely peripheral blood smear findings in this case
• A researcher measured hemoglobin, hematocrit, serum ferritin concentration,
and percent transferrin saturation in blood specimens from the regular blood
donors and comparable nondonors for many years. Over the period of the study,
mean iron stores in donors declined. Nondonors’ iron stores remained
unchanged. Based on hemoglobin and hematocrit results, no donors became
anemic. As iron stores decreased, the calculated iron absorption rose to more
than double the normal rate for the donors.
1. Why did the donors’ iron stores decrease?
2. Why did the donors’ iron absorption rate rise? Explain using the names of all
proteins involved.
3. Name the laboratory test(s) performed in the study used to evaluate directly
the iron storage compartment?
4. What is the diagnostic value of the percent transferrin saturation?
1. Iron loss via blood donations and normal physiologic loss was not
compensated by diet.
2. Adaptation to low iron levels. Iron stores of ferritin were mobilized first. But
when storage iron declined, hepcidin levels declined, and as a result,
duodenal iron absorption increased
3. Ferritin
4. Transferrin saturation is a calculation that relies on the serum iron value and
the total iron-binding capacity (TIBC). The serum iron reflects iron in transit in
the blood, whereas the TIBC reflects the number of transferrin binding site
available for iron; an indirect assessment of transferrin. The diagnostic value
of the % transferrin saturation is not as great as ferritin in assessing iron
stores, though the % transferrin saturation would be expected to decline as
iron stores decline.
• A 45-year-old woman phoned her physician and complained of fatigue, shortness
of breath on exertion, and general malaise. She requested “B12 shots” to make
her feel better. The physician asked the patient to schedule an appointment so
that she could determine the cause of the symptoms before offering treatment. A
point-of-care hemoglobin determination performed in the office was 9.0 g/dL.
The physician then requested additional laboratory tests, including a complete
blood count with a reticulocyte count and a peripheral blood film examination.
1. Why did the physician want the patient to come to the office before she
prescribed therapy?
2. How do the mean cell volume and reticulocyte count help determine the
classification of the anemia?
3. Why is the examination of the peripheral blood film important in the
investigation of an anemia?
1. Anemia is not a disease or diagnosis in itself but is the symptom of an
underlying disorder. A complete history and physical examination are
necessary to help identify the cause(s) of the anemia. If the underlying cause
is not determined and corrected, the patient will continue to be anemic.
2. Reticulocyte count differentiates anemias into those involving impaired
production (decreased count) and increased destruction (increased count).
Anemia can also be classified on the basis of MCV into normocytic, microcytic,
or macrocytic. With that knowledge, appropriate laboratory testing can be
ordered to determine the cause.
3. Peripheral blood film yields valuable information about the volume and Hb
content of erythrocytes as well as any abnormal shapes, which may be
correlated with specific causes. Some anemias are also associated with white
blood cell and/or platelet abnormalities, which may be noted in PBS.
• Which of the following are important to consider in the patient’s history when
investigating the cause of an anemia?

a. Diet and medications

b. Occupation, hobbies, and travel

c. Bleeding episodes in the patient or in his or her family members

d. All of the above

• Which one of the following conditions would be included in the differential
diagnosis of an anemic adult patient with a reticulocyte count of 0.1
millions/mm3, MCV of 65 Fl, RDW 18.5%, and a normal total leukocyte count.

a. Aplastic anemia

b. Sickle cell anemia

c. Iron deficiency

d. Thalassemia
• Which one of the following findings would be inconsistent with elevated titers
of intrinsic factor blocking antibodies?

a. Hypersegmentation of neutrophils

b. Increased reticulocyte count

c. Macrocytic RBCs

d. Low levels of vitamin B12

• Which of the following CBC findings is most suggestive of a megaloblastic
anemia?

a. MCV of 103 fL

b. Hypersegmentation of neutrophils

c. RDW of 16%

d. Hemoglobin concentration of 9.1 g/dL

• An old age male had difficulty in walking straight. The physician diagnosed peripheral
neuropathy. In addition, the physician noted that the patient was pale. After looking at
complete blood count (CBC) results physician advised vitamin assay.

1. Which of the CBC findings led the physician to order the vitamin assays?
2. Is the patient’s reticulocyte response adequate to compensate for anemia?
3. Why leucocyte and platelets count could be low?
4. What do you understand by RDW? In increased RDW, blood smear shows which type of
picture?
• The following are the features of megaloblast, EXCEPT:

A. Larger than normoblast

B. Nuclei have more open sieve-like chromatin

C. Cytoplasmic maturation lags behind nuclear maturation

D. Marrow shows increased proportion of more primitive erythroid cells

• The best and earliest hematological finding in megaloblastic anemia is:

A. Decreased hemoglobin

B. Decreased hematocrit

C. Hypersegmented neutrophils

D. Poikilocytosis

Sequence of development of Megaloblastic Anemias

PY 2.5: Describe different types of anemia's &
jaundice
After end of this lecture, you should be able to:

• Define jaundice

• Classify different types of jaundice

Bilirubin metabolism
1) Production in reticuloendothelial
system
2) Transport to liver
3) Hepatic uptake
4) Conjugation with glucuronic acid
5) Excretion into bile
6) Deconjugation and reduction in
intestine
 Jaundice

Serum bilirubin. The normal values are:

• Total serum bilirubin: 0.3–1.0 mg/dL

• Conjugated (direct) bilirubin: 0.1–0.3 mg/dL

• Unconjugated (indirect) bilirubin: 0.2–0.7 mg/dL

• Jaundice, also known as hyperbilirubinemia, is defined as a yellow discoloration

of the body tissue (icterus) resulting from the accumulation of excess bilirubin

• Icterus first seen in sclera → bilirubin >2-3 mg/dL

• Estimation of serum bilirubin is based on its reaction with diazo reagent (van den
Bergh reaction) to form purple colored azobilirubin
Urine bilirubin

• Unconjugated bilirubin always binds to albumin in the serum and is not filtered
by the kidney

• Bilirubinuria (dark urine) is due to conjugated bilirubin

• Patients with unconjugated hyperbilirubinemia do not have bilirubinuria

(‘acholuric jaundice’)
Fecal and urinary urobilinogen

• In distal ileum and colon, bilirubin (from bile) is broken down by gut bacteria into
urobilinogen

• A part of urobilinogen, which is absorbed in portal circulation is returned to liver

via enterohepatic circulation

• A small amount enters the systemic circulation and reaches kidney , where
urobilinogen is oxidized to a coloured pigment, urobilin, to be excreted in urine

• Rest is excreted in faeces as stercobilinogen that upon exposure to atmospheric

air, is oxidized to a coloured product, stercobilin
• Based on underlying causes, the jaundice is conventionally classified as

1. Hemolytic: increased hemoglobin breakdown produces bilirubin which

overloads the hepatic conjugating mechanism

2. Hepatic: damaged hepatocytes have impaired capacity to take up the

circulating bilirubin and to conjugate it

3. Obstructive: bile unable to reach duodenum due to obstruction

 Hemolytic Hepatic Obstructive

Serum unconjugated
Increased Increased Normal
bilirubin

Increased Increased
Serum conjugated Normal/mild (due to cholestasis (overflow into
bilirubin increase followed by leak into blood
blood*) circulation)
Urine, bilirubin Nil Present Present
Nil, Clay
Fecal, stercobilin Increased Decreased
coloured

Urine, urobilin Increased Decreased Nil

*Hepatic Jaundice
• Inflammatory edematous cells compress intracellular biliary canaliculi, and
this produces an element of obstruction

• Consequently, conjugated bilirubin formed in hepatocytes may leak out of

the damaged cells in blood circulation

• Conjugated bilirubin, therefore, appears in blood circulation in increased

amount
 Other biochemical tests

• Albumin level falls and globulin (γ) levels rise in hepatobiliary diseases of
substantial duration and severity. Reversal of A:G ratio (normal 1.7:1).

• Prolonged prothrombin time (PT collectively measures factors II, V, VII, and X;
normal 10–16 s) indicates severe liver disease
 Serum Enzymes
• Serum enzyme tests can be grouped into two categories:

1) Enzymes whose elevation in serum reflects damage to hepatocytes:

Transaminases (SGPT or ALT, and SGOT or AST)

2) Enzymes whose elevation in serum reflects cholestasis: ALP, GGT

SGPT: serum glutamate pyruvate transaminase

ALT: alanine transaminase
SGOT: serum glutamic oxaloacetic transaminase
AST: aspartate transaminase
ALP: alkaline phosphatase
GGT: γ-glutamyl transferase
• AST is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas,
lungs, leukocytes, and erythrocytes in decreasing order of concentration

• ALT is found primarily in the liver and is therefore a more specific indicator of liver
injury

• ALP are found in or near the bile canalicular membrane of hepatocytes, whereas
GGT is located in the endoplasmic reticulum and in bile duct epithelial cells

• GGT elevation in serum is less specific for cholestasis than are elevations of ALP

• GGT is used as an indicator of alcoholic liver disease

• The normal serum ALP consists of many distinct isoenzymes found in the liver,
bone, placenta, and, less commonly, in the small intestine

• ALP can rise 3X in almost any liver disease. 4X rise suggests cholestasis

• In the absence elevated aminotransferases, an elevated ALP suggests cholestasis

3 4
Extravascular hemolysis Intravascular hemolysis
Macrophages in liver, spleen, and bone
marrow removes RBCs from circulation RBCs rupture in vessels and release Hb
by phagocytosis directly into circulation

Unconjugated hyperbilirubinemia Reduced or absent serum haptoglobin

Hemoglobinemia, hemoglobinuria,
Splenomegaly
hemosiderinuria, methemoglobinemia

Reticulocytosis Reticulocytosis

RBCs fragments (Schistocytes)

• The type of jaundice associated with increased urobilinogen without bilirubin
in urine is:

A. Acholuric (without bile in urine)

B. Obstructive

C. Hepatitis associated

D. HIV associated
• A 50-year-old male, visited his doctor when he noted that the whites of his eyes
appeared yellow and that he had dark urine. His CBC results were hemoglobin 8.4
g/dL, hematocrit 21%, RBC count 3 millions/mm3, RDW 20%, reticulocyte count
12%. His blood smear revealed marked spherocytosis.
1. Calculate the erythrocyte indices.
2. Explain the importance of peripheral blood smear finding.
3. Explain why patient had yellow coloured eye and dark urine.

70 fl

28 pg

40%
• Why might the serum bilirubin results be misleading as an indicator of
erythrocyte destruction in patients with microcytic hypochromic anemias?

a. The liver is not excreting the bilirubin due to liver failure

b. The cells are being produced at a lower rate than normal

c. Hypochromic cells do not release much hemoglobin; hence, less bilirubin is

formed

d. The cells are not destroyed as fast in individuals with microcytic anemia so
the bilirubin will be falsely decreased