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Formal Written Output in Physiology

PROBLEM BASED LEARNING

Submitted to: Dr. Lizalyn Marie Revilla and Dr. Leo Emmanuel Bunag

Submitted by:

BASANGAN, Ajay

CO, Steffi Rosanna G.CUMIGAD, Dorothy Joy

FERNANDEZ, John Philip

MARIADASS, Mary Jenova

OILLAS,Jyn Desire

RAGUINDIN, Erica Joy

Saint Louis University

School of MedicineOctober 09, 2014

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CASE 1

A 30 year old woman has had a constant feeling of lethargy since childhood. On Physical examination,

she is afebrile and has a pulse of 80/min, respirations of 15/min and a blood pressure of 110/70 mmhg.

The spleen tip is palpable, but there is no abdominal pain or tenderness. Laboratory studies show

hemoglobin of 10.0 g/dl. Platelet count of 159,000/mm3, and RBC count of 3800/mm3. The peripheral

blood smear shows spherocytosis. The circulating RBCs show an increased osmotic fragility.

1.

What is the Diagnosis?

Hereditary Spherocytosis (Chronic Hemolytic Anemia)

2.

Explain the increased osmotic fragility of the red blood cells.

Increased Osmitic Fragility happens when the blood cell is placed in water, they are more likely

to burst than normal RBCs. This is caused by a molecular defect in one or more of the proteins of

RBC cytoskeleton, including Spectrin and Ankyrin, Band 3 or Protein 4.2. Because the

cytoskeleton has a defect, the blood cell contracts to its most surface tension efficient and least

flexible configuration, a sphere, which are more prone to physical degradation.

3. Explain the laboratory findings in correlation with the disease of the patient.

Result Normal Value Interpretation Explanation

RBC Count 3,800/mm3 3.6-5.0

million/mm3

Decreased RBC Count is decreased because

in hereditary spherocytosis, the

cells are very small and

spherical. They cannot withstand

compression forces. On passing

thru the splenic pulp and some

other tissues, they are easily

ruptured by even the slightest

compression.

Hemoglobin 10.0 g/dL 12-15g/dL Decreased A low hemoglobin count can be

due to blood loss since

hemoglobin is carried inside the

RBCs. In this case, the decreased

value is due to the destruction of

the RBCs.Platelent

Count

159,000/mm3 150,000-

400,000

Normal The patients platelet count is

normal because the only cells

involved in hereditary

spherocytosis are the red blood

corpuscles.

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4. Compare the patients abnormality in RBC morphology with the following conditions:

Anemia Morphology

Iron deficieny Anemia The shape of the RBC in IDA is normal, the anemia

is caused by the deficiency in Iron which is

important for the formation of hemoglobin

Anemia of Chronic Disease Chronic diseases interfere with the bodys ability

to use stored iron and absorb iron from the diet.

The body cannot respond normally to

erythropoietin, a hormone made by the kidneys

that stimulates bone marrow to produce red blood

cells. Over time, this abnormal functioning causes

a lower than normal number of red blood cells in

the body.

Hereditary Elliptocytosis There is a large number of elliptically shaped

erythrocytes which predisposes to hemolytic

anemia causing splenomegaly

Sickle cell Anemia Erythrocytes are crescent-shaped due to theabnormality in the oxygen carrying molecule. The

amino acid valine is substituted for glutamic acid

at one point in each of the two beta chains. When

this type of hemoglobin is exposed to low oxygen,

it forms elongated crystals inside the RBCs that

makes it impossible to pass through small

capillaries, and the spiked ends of the crystals are

most likely to rupture the cell membranes, thus

leading to sickle cell anemia.

CASE 2

A 39-year old woman sees her physician because she has experienced abdominal pain and

intermittent low volume diarrhea for the past 3 months. On physical examination, she is afebrile. A stool

sample is positive for occult blood. A colonoscopy is performed and biopsy findings from the terminal

ileum are removed. She is transfused with two units of packed RBCs during surgery. Several weeks later,

she appears healthy but complains of easy fatigability. On investigation, CBC findings show hemoglobinof 10.6 g/dL, hematocrit 31.6%, RBC count 2.69 million/uL, MCV 118 um

3, platelet count 378,000/mm

3,

and WBC count 9800/mm3.

1.

What disease is most likely to produce the above clinical and laboratory manifestations?

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Pernicious anemia, a form of Vitamin B12 Deficiency Anemia, is the most likely diagnosis

of the patient. It is caused by a deficiency of intrinsic factor, a glycoprotein produced by the

parietal cells of the stomach.It is necessary for the absorption of vitamin B12 later on in the

small intestine. It attaches itself to the Vitamin B12, and both are absorbed in combination into

the lowest portion of the small intestine (ileum).

Vitamin B12 is necessary for the production of RBCs. Proper production of RBCs

depends on adequate deoxyribonucleic acid (DNA) synthesis in the precursor cells so that cell

division and growth into functional RBCs can occur. One function of Vitamin B12 is to activate

the enzymes that move folic acid into the cell, where DNA synthesis occurs. Vitamin B12

deficiency causes anemia by inhibiting folic acid transport and reducing DNA synthesis in

precursor cells.

But since the patient underwent a surgical procedure to remove his ileum, the intrinsic

factor and Vitamin B12 are not being properly absorbed. Due to the decreased absorption of

Vitamin B12, there is also a decrease in RBC production which further leads to anemia.

2.

Interpret and explain the laboratory result of the patient.

Result Normal Value Interpretation Explanation

Hemoglobin 10.6 g/dL 12-15g/dL Decreased Due to the decreased RBC,

hemoglobin and hematocri

concentration also decreas

Hematocrit 31.6% 37-47% Decreased Due to the decreased RBC,

hemoglobin and hematocri

concentration also decreas

RBC Count 2.69 milion/uL 3.6-5.0

million/mm3

Decreased Due to the decreased Vitam

B12 absorption, there is als

decrease in RBC production

Therefore showing a low R

count

MCV 118 um3 85-100 um

3 Increased Due to Vitamin B12 deficie

folic acid transport is inhibi

and DNA synthesis in precu

cells is reduced. These prec

cells then undergo imprope

synthesis. The cell cycle can

progress from the G2 growstage to the mitosis stage. T

leads to continuing cell gro

without division, which pre

as macrocytosis.

Platelent Count 378,000/mm3 150,000-

400,000

Normal Vitamin B12 deficiency has

direct effect on platelets.

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WBC Count

9800/mm3

5,000-

10,000/mm3

Normal Vitamin B12 deficiency has

direct effect on WBCs.

3.

What is occult blood test? Explain its uses and limitations.

The fecal occult blood test (FOBT) is used to find occult blood (or blood that cant be

seend with the naked eye) in the stool. The idea behind this test is that blood vessels at the

surface of larger polyps or cancers are often fragile and easily damaged by passing stool. The

damaged blood vessels usually release a small amount of blood into the stool, but only rarely is

there enough bleeding to be visible in the stool. The FOBT is an easy way to determine whether

this is blood or not.

FOBT is commonly used as a screening test for colorectal cancer and polyps. But FOBT

has some limitations, it can yield a false-positive result if certain foods, vitamins or drugs (e.g.

Aspirin) are ingested before the test because these can cause irritation to the digestive tract. It

can also yield a false-negative result when screening for cancer or polyps, because these may

actually be present but still shows a negative result especially if the cancer or the polyps dont

bleed.

Case 3

A 37 years old male seeks consult due to recurrent lowgrade fever,night sweats which started 2years

PTC. A previousconsultant with anothther doctor was done, where he was managed as PTB case. He

finished a one year antiTB regimen but there was no improvement noted. 2months PTC, heloss a

significant weight.PE shows inguinal lymphadenopathy as well as splenomegaly.

CBC result is a follows:

Hemoglobin 80

Haematocrit 23

WBC count 223x 10 9/L

Differntial count:

Neutrophils 20%

Bands 10%

Lymphocytes 4%

Eosinophils 2%

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Eosinophils 2%

Promyelocytes 10%

Myelocytes 18%

Metamyelocytes 15%

Blasts 5%

A bone marrow smear was performed with the following results:

Markedly hyper cellular marrow withpredominance of granulocytes with intermediate degrees of

maturity

Mild marrow fibrosis

1.

Illustrate how white blood cells are formed.

Early differentiation of the pluripotential hematopoieticstem cell into the different types

of committedstem cells is shown in Figure 1. From the PHSC there is aformation of CFU-S

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formthat point Granulocytes and monocytes are forming.undergranulocytes there are

Neutrophils,Eosinophils and Basophils.this monocytes become macrocytes.

Form the CFU- s there is a formation of CFU-M . itwillform the Megqakaryocytes. This will

responsible for Platelets.

Aside from those cells committed to form redblood cells, two major lineages of white

blood cells areformed, the myelocytic and the lymphocytic lineages.

The left side of Figure 331 shows the myelocyticlineage, beginning with the myeloblast; the

rightshows the lymphocytic lineage, beginning with thelymphoblast.

The granulocytes and monocytes are formed onlyin the bone marrow. Lymphocytes and

plasma cells are produced mainly in the various lymphogenoustissuesespecially the lymph

glands, spleen, thymus,tonsils, and various pockets of lymphoid tissueelsewhere in the body,

such as in the bone marrow and in so-called Peyers patches underneath the epithelium in the

gut wall.

The white blood cells formed in the bone marroware stored within the marrow until they are

needed inthe circulatory system. Then, when the need arises,various factors cause them to be released

(thesefactors are discussed later). Normally, about threetimes as many white blood cells are stored in

themarrow as circulate in the entire blood.This representsabout a 6-day supply of these cells.The

lymphocytes are mostly stored in the variouslymphoid tissues, except for a small number that

aretemporarily being transported in the blood. As shown in Figure 2, megakaryocytes are also formed in

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1 Marked hyper cellular marrow Abnormal increase in

number of cell

present in bone

marrow

2 Predominance of granulocytes with

Intermittent degree of maturity

Increase number of

Neutrophil, Basophil

and Eosinophil.

Bone Marrow

Granulocytes normal

range :

Neutrophil: 12.0

34.0%

Basophil : 0.01.0%

Eosinophil: 0.07.0 %

3 Mild Marrow fibrosis. Scaring of the Bone

marrow

Normal Bone Marrow

Chronic Myeloid Leukemia Bone Marrow

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This high power view of the bone marrow shows a cluster of small megakaryocytes, a

characteristic feature of CML. This marrow also showed increased numbers of granulocytic

precursors in all stages of maturation, with less that 5% blasts.

3.

What is the Diagnosis?

S.No Book Picture Patient Picture

1 Fatigue

Weight Loss

Loss of Energy

Decreased Exercise tolerance

Weight loss

2 Low-grade fever and excessive Night sweating from hyper

metabolism

Low-grade fever

and night Sweating3 Increase WBC and Splenomegaly Increase WBC

Splenomegaly

4 Early satiety and decreased food intake from encroachment on

stomach by enlarged spleen

5 Left upper quadrant abdominal pain from spleen infarction

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6 Hepatomegaly

8 Increasing anaemia Decrease Hb

9 In the Blood presence of Early myeloid cells (eg, myeloblasts,

myelocytes, metamyelocytes, nucleated red blood cells)

Myeloblasts

MyelocytesMetamyelocytes

10 Bone Marrow Smear : Hypercellularity, with expansion of the

myeloid cell line (eg, neutrophils, eosinophils, basophils) and its

progenitor cells

Granulocytes

present

11 Mild fibrosis in the reticulin stain Mild Fibrosis

present

12 It account for 20 % Adult Leukemias Patient age 37Years

Patient Diagnosis: Chronic myelogenous leukemia (CML)

CASE 4

A 69 year old previously healthy woman has been feeling increasingly tired and weak for 4 months. She

has been complaining of off and on epigastric pain, and on occasion, noted black tarry stools. On PE, she

is afebrile. There is no hepatosplenomegaly or lymphaedenopathy. Laboratory studies show hg of 9.3

g/dl, platelet count 250,600 mm3, and wbc count of 6.8 x 10/L. the peripheral smear microcytic and

hypochromic. Hemoglobin electrophoresis is normal.

1. What is the diagnosis?

Iron deficiency anemia resulted to microcytic hypochromic anemia

We came up with this diagnosis, because the patient manifested chronic weakness and fatigue, this is

probably caused by decreased hemoglobin level in the body which resulted to hypoxia in the nervous

and systemic circulation. The patient also manifested black tarry stools which is one of the main markers

of iron deficiency anemia.

2. Explain how iron is stored, transported and utilized?

Almost 65 percent of the total iron in the body is in the form of hemoglobin. About 4 percent of it is in

the form of myoglobin, 1 percent for various heme compounds that promote intracellular oxidation, 0.1

percent is combined with the protein transferrin in the blood plasma, and quarter of it is stored for lateruse as form of ferritin, mainly in the reticuloendothelial system and liver parenchymal cells.

Iron immediately combines in the blood plasma with a beta globulin after it is absorbed in the

duodenum, apotransferrin, to form transferrin, which is then transported in the plasma. Loosely

bounded iron in the transferrin released to any tissue cell at any point in the body. Excess iron in the

blood is deposited especially in the liver hepatocytes and less in the reticuloendothelial cells of the bone

marrow.

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Iron combines mainly with a protein in the cytoplasm, apoferritin, to form ferritin. Ferritin may contain

only a small amount of iron or a large amount depending on the varying quantities of iron that can

combine in clusters of iron radicals with large molecule. The iron stored as ferritin is called storage iron

and in extremely insoluble form is called hemosiderin which is in small quantities.

Ferritin provides rapidly available stores of iron whereas iron mobilization from hemosiderin is muchslower approx. 250mg Fe in macrophages of the liver and bone marrow. Hb-Fe and heme-Fe released

from malformed erythroblasts and hemolyzed red blood cells bind to haptoglobin and hemopexin,

respectively then engulfed by macrophages in the bone marrow or in the liver and spleen, respectively,

resulting in 97% iron recycling.

3. Explain the laboratory results in the light of the patients disease?

Iron deficiency anemia is diagnosed by blood test that includes complete blood count (CBC). These tests

usually reveal relevantly low hemoglobin count and hematocrit levels as manifested by the patient.

Additional test may be ordered to evaluate the levels of serum ferritn, iron levels and fecal occult blood

test. In the peripheral smear of the patient, the result signifies that iron deficiency anemia affected the

morphological structure of the cell that resulted to microcytic and hypochromic erythrocytes. White

blood cell count and platelet count is in normal range, it means that theres no associated infection and

blood coagulation problems or bleeding

4. How is hemoglobin formed?

Hemoglobin formation

Hemoglobin synthesis starts in proerythroblasts or even into the reticulocyte stage of the red blood

cells. When reticulocytes leave the bone marrow and pass into the blood stream, they continue to form

minute quantities of hemoglobin for another day or so until they become mature erythrocytes.

Biochemical processes is essentially involved in the formation of hemoglobin which includes binding of

succinyl-CoA with glycine to form a pyrrole molecule in the first process. In turn, four pyrroles combine

to form protoporphyrin IX, which then combines with iron to form the heme molecule. Finally, each

heme molecule combines with globin synthesized by ribosomes, forming a subunit of hemoglobin called

a hemoglobin chain which four of these in turn bind together loosely to form the whole hemoglobin

molecule. Variation in the different subunit hemoglobin chain depends on the amino acid composition

of the polypeptide portion. The different types of chains are designated alpha chains, beta chains,

gamma chains, and delta chain which makes hemoglobinA, common form of hemoglobin in the adult

human being that hasa combination of two alpha chains and two beta chains. The types of hemoglobinchains in the hemoglobin molecule determine the binding affinity of the hemoglobin for oxygen.

Because each hemoglobin chain has a heme prosthetic group containing an atom of iron, and because

there are four hemoglobin chains in each hemoglobin molecule, one finds four iron atoms in each

hemoglobin molecule; each of these can bind loosely with one molecule of oxygen, making a total of

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four molecules of oxygen (or eight oxygen atoms) that can be transported by each hemoglobin

molecule.

References

Costano, Linda S. Physiology:Cases and Problems 4th Edition. Retrieved from

https://www.inkling.com/read/physiology-cases-problems-linda-costanzo

Hall, John. 2011. Guyton and Hall Textbook of Medical Physiology, 12th

Edition. USA:Saunders

Koeppen, Bruce. 2010. Berne & Levy Physiology, 6th

Updated Edition.Canada: Mosby Inc.

https://www.inkling.com/read/physiology-cases-problems-linda-costanzohttps://www.inkling.com/read/physiology-cases-problems-linda-costanzo