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 Medicine October 09, 2014
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/mm 3
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/mm 3 150,000- 400,000 Normal
The patients platelet count is normal because the only cells involved in hereditary spherocytosis are the red blood corpuscles.
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 the abnormality 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 hemoglobin of 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/mm 3 .
1. What disease is most likely to produce the above clinical and laboratory manifestations?
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 hematocrit concentration also decreases. Hematocrit 31.6% 37-47% Decreased Due to the decreased RBC, hemoglobin and hematocrit concentration also decreases. RBC Count 2.69 milion/uL 3.6-5.0 million/mm 3
Decreased Due to the decreased Vitamin B12 absorption, there is also a decrease in RBC production. Therefore showing a low RBC count MCV 118 um 3 85-100 um 3 Increased Due to Vitamin B12 deficiency, folic acid transport is inhibited and DNA synthesis in precursor cells is reduced. These precursor cells then undergo improper DNA synthesis. The cell cycle cannot progress from the G2 growth stage to the mitosis stage. This leads to continuing cell growth without division, which presents as macrocytosis. Platelent Count 378,000/mm 3 150,000- 400,000 Normal
Vitamin B12 deficiency has no direct effect on platelets.
WBC Count 9800/mm 3
5,000- 10,000/mm 3
Normal Vitamin B12 deficiency has no 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 low grade 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 anti TB 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% 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 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
the bone marrow.These megakaryocytesfragment in the bone marrow; the small fragments,known as platelets (or thrombocytes), then passinto the blood. They are very important in the initiation of blood clotting.
2. Are the Complete blood count result of your patient normal? Complete Blood Count S.No Component Patient Value Normal Value Remark 1 Hemoglobin
80 Male: 135 165 g Female: 120 150g Decreased Haematocrit
223 x 10 9/L 4.5 10.0 x 10 9/L Increased Differential count:
Neutrophils
20%
54 62%
Decreased Bands
10% 3 5%
Increased Lymphocytes
4%
24 44 % Decreased Eosinophils
2% 0 3 % Normal Basophils
6% 0 1% Increased Promyelocytes
10% 0% Bone Marrow: 1.0 8.0 % Abnormal Present Myelocytes
18% 0% Bone Marrow: 5.0 19.0 % Abnormal Present Metamyelocytes
15% 0% Bone Marrow: 13.0 22.0 % Abnormal Present Blasts
5% 0% Bone Marrow: 0.0 5.0 % Abnormal Present
Bone Marrow Smear S.no Patient Value 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 : 0.0 1.0% Eosinophil: 0.0 7.0 % 3 Mild Marrow fibrosis.
Scaring of the Bone marrow
Normal Bone Marrow
Chronic Myeloid Leukemia Bone Marrow
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 Sweating 3 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
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 Myelocytes Metamyelocytes 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 later use 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. 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 much slower 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 hemoglobin A, common form of hemoglobin in the adult human being that has a combination of two alpha chains and two beta chains. The types of hemoglobin chains 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 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, 12 th Edition. USA:Saunders Koeppen, Bruce. 2010. Berne & Levy Physiology, 6 th Updated Edition. Canada: Mosby Inc.