Answer

Pernicious Anemia

Abstract

Teri presented to her PCP with chief two complaints including feeling depressed for the last couple of months and a seizure. Lab results included low levels of vitamin B12, low hematocrit, low oxygen levels, and presence of autoantibodies against the parietal cells. Besides, peripheral blood smear showed abnormal red blood cells – large pale red blood cells. Teri was diagnosed with pernicious anemia. 

Introduction

            The purpose of this essay is to provide an explanation on the pathophysiological basis of the observed signs and symptoms in Teri’s case. The scope of this discussion includes the consequences of autoimmune destruction of parietal cells and its association with pepsin deficiency. The normal appearance of red blood cells (RBCs) and a definition of hematocrit are also provided in the body of this essay. The discussion also discusses the basis of increased RBCs production in relation with low oxygen levels and the structure of hemoglobin. Other issue discussed herein is antibody production. Teri’s diagnosis of pernicious anemia is associated with vitamin B12 deficiency. 

Autoimmune Destruction of Parietal Cells

            Autoimmune gastritis is chronic inflammatory condition that is characterized by destruction of parietal cells of the fundus and corpus of the stomach. The known consequence of destruction of parietal cells is deficiency of vitamin B12, which results in development of pernicious anemia. In addition, destruction of parietal cells is associated with reduction in production of gastric acid. Gastric acid is necessary for the absorption of inorganic iron. This can also result in iron deficiency, which is a common presentation in patients with autoimmune gastritis (Kulnigg-Dabsch, 2016). On the other hand, low secretion of gastric acid is associated with lack of pepsin. Pepsinogen, inactive form of pepsin, is secreted by gastric chief cells. A low gastric pH (1.5 to 2) offered by gastric acid facilitates activation of pepsinogen into pepsin. Therefore, in Teri’s case low levels or lack of gastric acid due to autoimmune destruction of parietal cells has resulted in lack of pepsin (Hada, Toro, & Tombazzi, 2020).

Red Blood Cells (RBCs)

            If Teri’s RBCs were healthy, they could have appeared like puffy discs with concave depressions on the top and bottom. RBCs can change shape as they squeeze through narrow capillaries (Scipps Research Institute, 2018). Oxygenated RBCs appears bright red while deoxygenated RBCs appear dark red. On the other hand, normal RBCs are described as normocytic (normal size) and normochromic (normal color or normal hemoglobin concentration) cells (LabCE, 2021). Hemoglobin test measures the level of hemoglobin circulation. The normal range for hemoglobin for is 12.0 to 15.5 g/dL in women and 13.5 to 17.5 g/dL in men. Normal hemoglobin ranges for children varies with sex and age. Higher than normal levels of hemoglobin is due to polycythemia vera, lung disease, dehydration, heavy smoking, burns, excessive vomiting, living at a high altitude, and extreme physical exercise. On the other hand, lower than normal results for hemoglobin is caused by iron deficiency, bleeding, folate deficiency, vitamin B12 deficiency, cancers of the bone marrow such as leukemia, hypothyroidism, liver disease, kidney disease and thalassemia (Mayo Clinic, 2019). 

Hematocrit

            Hematocrit is a measure of the volume of packed RBCs relative to whole blood. It is also reported or described as packed cell volume. It is a simple test for detecting conditions such as polycythemia and anemia and for determining response to treatment. A normal adult female shows a hematocrit value of 36% – 48% and male shows 40% – 54% (Mondal & Budh, 2020).

Erythropoiesis

            Low oxygen levels stimulate erythropoiesis, which is the process of production of new RBCs in the bone marrow. Erythropoiesis occurs in the bone marrow under the control of erythropoietin hormone. The juxtaglomerular cells localized in the kidneys secretes erythropoietin in response to hypoxia or decreased oxygen delivery. Conditions such as anemia can also induce increased secretion of erythropoietin. Besides, increased levels of androgens can also induce secretion of erythropoietin. Apart from presence of erythropoietin, RBC production also requires the presence of vitamin B12, iron, heme, and folate. RBCs survive for approximately120 days (MERCK Manual, 2020).

Hemoglobin

            The protein that transports oxygen in the human body is known as hemoglobin. Its structure is described as the heme containing globulin proteins. Hemoglobin is tetramer that contains two α-subunits (α₁ and α₂) and two β-subunits (β₁ and β₂), which are structurally similar and about the same size. They are organized into two αβ dimers (named α₂β₂ and α₁β₁) that arranged around a two-fold-axis of symmetry leading into formation of a large central water cavity in the unliganded or T or deoxygenated structure and a narrower cavity in the liganded or R or oxygenated structure. Each of the α-subunits and β-subunits consist of a binding pocket for heme molecule. Heme comprise of a ferrous iron that is coordinated by four nitrogen atoms of the porphyrin ring and held in the center of a porphyrin (Ahmed & Ghatge, 2020).

Antibodies

            Antibodies or immunoglobulins (Ig) are glycoproteins, which are produced by plasma cells. Plasma cells are sensitized B cells. B cells participate as part of the humeral immune response by producing Igs in response to viruses, bacteria, parasites, fungi, chemicals, cellular antigens, and synthetic substances. Igs have two heavy chains and two light chains arranged in a light-heavy-heavy-light structure. The heavy chains seem to differ among classes. Igs have one Fab region, where an antigen binds and a Fc region, which mediates biological factions such as binding of the Ig to cellular receptors. All Igs demonstrate one or more functions including opsonization of microbes so as to be easily phagocytized, activation of the complement system, neutralization of viruses and toxins, and prevention of attachment of microbes to mucosal surfaces. There are five types of Igs, which include IgM, IgG, IgA, IgE,and IgD. IgM has a molecular weight of 970 kD and serum concentration is 1.5 mg/mL. IgM is produced in primary response to antigens or infectious agents. IgG has a molecular weight of 146 kD and serum concentration is 9.0 mg/mL; produced in secondary response to antigens or infectious agents. IgA has molecular weight of 160 kD and its serum concentration is 3 mg/mL; secreted in tears, saliva, colostrum, and respiratory, intestinal, and genital tract secretions. IgE is a monomer with a molecular weight of 188 kD and serum concentration of 0.00005 mg/mL; protects against parasitic infections. IgD is a monomer with molecular weight of 184 kD and serum concentration of 0.03 mg/mL; has unknown functions against pathogens (Vaillant, Jamal, & Ramphul, 2021).

Conclusion

            Autoimmune destruction of parietal cells can lead to vitamin B12 and iron deficiency. Antibodies are produced by sensitized B cells known as plasma cells. Besides, it can lead to low (or no) secretion of gastric acid that results in failure of activation of pepsinogen. Vitamin B12 deficiency is associated with development of pernicious anemia. On the other hand, hypoxia can increase secretion of erythropoietin hormone in the juxtaglomerular cells in the kidneys; erythropoietin in turn stimulates the process of erythropoiesis in the bone marrow to increase hematocrit levels. Hemoglobin is a protein that transports oxygen in the body and is made up of two α-subunits, two β-subunits, and a heme group.