RESOURSES: McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). St. Louis, MO: Mosby/Elsevier.
• Chapter 24: Structure and Function of the Reproductive Systems (stop at Tests of reproductive function); Summary Review
• Chapter 25: Alterations of the Female Reproductive System (stop at Organ prolapse); pp. 787–788 (start at Impaired fertility) (stop at Disorders of the female breast); Summary Review
• Chapter 26: Alterations of the Male Reproductive System (stop at Hormone levels); Summary Review
• Chapter 27: Sexually Transmitted Infections, including Summary Review
• Chapter 28: Structure and Function of the Hematological System (stop at Clinical evaluation of the hematological system); Summary Review
• Chapter 29: Alterations of Erythrocytes, Platelets, and Hemostatic Function, including Summary Review
• Chapter 30: Alterations of Leukocyte and Lymphoid Function, including Summary Review
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Low, N. & Broutet N. J. (2017). Sexually transmitted infections – Research priorities for new challenges. PLoS Medicine, (12), e1002481
Kessler, C. M. (2019). Immune thrombocytopenic purpura [LK1] (ITP). Retrieved from https://emedicine.medscape.com/article/202158-overview
Nagalia, S. (2019). Pernicious anemia[LK1] . Retrieved from https://emedicine.medscape.com/article/204930-overview#a3
Stauder, R., Valent, P., & Theurl, I. [LK1] (2019). Anemia at older age: Etiologies, clinical implications and management. Blood Journal, 131(5). Retrieved from http://www.bloodjournal.org/content/131/5/505?sso-checked=true
Credit Line: Anemia at older age: Etiologies, clinical implications and management by Stauder, R., Valent, P., & Theurl, I., in Blood Journal, Vol. 131/Issue 5. Copyright 2019 by American Society of Hematology. Reprinted by permission of American Society of Hematology via the Copyright Clearance Center.
CASE: PERNICIOUS ANEMIA CASE
Scenario 3: 67-year-old female presents with chief complaint of shortness of breath, fatigue, weakness, unintentional weight loss, and mild numbness in her feet. She states she feels unsteady when she walks. PMH includes hypothyroidism well controlled on Synthroid 100 mcg/day. No hx of HTN or CHF.
Vital signs: Temp 98.7 F, pulse 118, Respirations 22, BP 108/64, PaO2 95% on room air.
Physical exam revealed pale, anxious female appearing older than stated years.
HEENT- pale conjunctiva of eyes and pale palate. Tongue beefy red and slightly swollen with loss of normal rugae. Turbinates pale but no swelling. Thyroid palpable but no nodules felt. No lymph nodes palpated.
Cardiac-regular rate and rhythm with soft II/VI systolic murmur. Respiratory- lungs clear with no adventitious breath sounds. Abdomen-soft, non-tender with positive bowel sounds. Liver edge palpated two finger breadths below right costal margin. Lab data- hgb, hct, reticulocyte count, serum B12 levels low, mean corpuscle volume, plasma iron, and ferritin levels high, folate, TIBC are normal.
Pernicious Anemia
Updated: Feb 18, 2019
• Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Emmanuel C Besa, MD more…
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Pathophysiology
Classic pernicious anemia is caused by the failure of gastric parietal cells to produce sufficient IF (a gastric protein secreted by parietal cells) to permit the absorption of adequate quantities of dietary vitamin B12. Other disorders that interfere with the absorption and metabolism of vitamin B12 can produce cobalamin deficiency, with the development of a macrocytic anemia and neurologic complications.
Cobalamin is an organometallic substance containing a corrin ring, a centrally located cobalt atom, and various axial ligands (see the image below).
Pernicious anemia. The structure of cyanocobalamin is depicted. The cyanide (Cn) is in green. Other forms of cobalamin (Cbl) include hydroxocobalamin (OHCbl), methylcobalamin (MeCbl), and deoxyadenosylcobalamin (AdoCbl). In these forms, the beta-group is substituted for Cn. The corrin ring with a central cobalt atom is shown in red and the benzimidazole unit in blue. The corrin ring has 4 pyrroles, which bind to the cobalt atom. The fifth substituent is a derivative of dimethylbenzimidazole. The sixth substituent can be Cn, CC3, hydroxycorticosteroid (OH), or deoxyadenosyl. The cobalt atom can be in a +1, +2, or +3 oxidation state. In hydroxocobalamin, it is in the +3 state. The cobalt atom is reduced in a nicotinamide adenine dinucleotide (NADH)–dependent reaction to yield the active coenzyme. It catalyzes 2 types of reactions, which involve either rearrangements (conversion of l methylmalonyl coenzyme A [CoA] to succinyl CoA) or methylation (synthesis of methionine).
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The basic structure known as vitamin B12 is solely synthesized by microorganisms, but most animals are capable of converting vitamin B12 into the two coenzyme forms, adenosylcobalamin and methylcobalamin. The former is required for conversion of L- methylmalonic acid to succinyl coenzyme A (CoA), and the latter acts as a methyltransferase for conversion of homocysteine to methionine.
When either cobalamin or folate is deficient, thymidine synthase function is impaired. This leads to megaloblastic changes in all rapidly dividing cells because DNA synthesis is diminished. In erythroid precursors, macrocytosis and ineffective erythropoiesis occur.
Severe neurological impairment, usually subacute combined system degeneration, occurs in cobalamin deficiency. However, vitamin B12 deficiencies can also present as peripheral neuropathy, psychosis, or leukoencephalopathy. Cobalamine neurological disorders can occur independently of hematological manifestations of pernicious anemia. The biochemical impairment in neurological degeneration may differ from hematological changes. [2]
Dietary cobalamin is acquired mostly from meat and milk and is absorbed in a series of steps, which require proteolytic release from foodstuffs and binding to IF. Subsequently, recognition of the IF-cobalamin complex by specialized ileal receptors—cubilin receptors—must occur for transport into the portal circulation to be bound by transcobalamin II (TCII), which serves as the plasma transporter.
The cobalamin-TCII complex binds to cell surfaces and is endocytosed. The transcobalamin is degraded within a lysozyme, and the cobalamin is released into the cytoplasm. An enzyme-mediated reduction of the cobalt occurs with either cytoplasmic methylation to form methylcobalamin or mitochondrial adenosylation to form adenosylcobalamin.
Defects of these steps produce manifestations of cobalamin dysfunction. Most defects become manifest in infancy and early childhood and result in impaired development, mental retardation, and a macrocytic anemia. Certain defects cause methylmalonic aciduria and homocystinuria. See the image below.
Pernicious anemia. Inherited disorders of cobalamin (Cbl) metabolism are depicted. The numbers and letters correspond to the sites at which abnormalities have been identified, as follows: (1) absence of intrinsic factor (IF); (2) abnormal Cbl intestinal adsorption; and (3) abnormal transcobalamin II (TC II), (a) mitochondrial Cbl reduction (Cbl A), (b) cobalamin adenosyl transferase (Cbl B), (c and d) cytosolic Cbl metabolism (Cbl C and D), (e and g) methyl transferase Cbl utilization (Cbl E and G), and (f) lysosomal Cbl efflux (Cbl F).
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Pernicious anemia probably is an autoimmune disorder with a genetic predisposition. The disease is more common than is expected in families of patients with pernicious anemia, and it is associated with human leukocyte antigen (HLA) types A2, A3, and B7 and type A blood group.
Antiparietal cell antibodies occur in 90% of patients with pernicious anemia but in only 5% of healthy adults. Similarly, binding and blocking antibodies to IF are found in most patients with pernicious anemia. A greater association than anticipated exists between pernicious anemia and other autoimmune diseases, including thyroid disorders, type 1 diabetes mellitus, ulcerative colitis, Addison disease, infertility, and acquired agammaglobulinemia. An association between pernicious anemia and Helicobacter pylori infections has been postulated but not clearly proven.
Cobalamin deficiency may result from dietary insufficiency of vitamin B12; disorders of the stomach, small bowel, and pancreas; certain infections; and abnormalities of transport, metabolism, and utilization (see Etiology). Deficiency may be observed in strict vegetarians. [3] Breastfed infants of vegetarian mothers also are affected. Severely affected infants of vegetarian mothers who do not have overt cobalamin deficiency have been reported.
Meat and milk are the main source of dietary cobalamin. Because body stores of cobalamin usually exceed 1000 µg and the daily requirement is about 1 µg, strict adherence to a vegetarian diet for more than 5 years usually is required to produce findings of cobalamin deficiency.
Classic pernicious anemia produces cobalamin deficiency due to failure of the stomach to secrete IF (see the image below).
Pernicious anemia. Cobalamin (Cbl) is freed from meat in the acidic milieu of the stomach where it binds R factors in competition with intrinsic factor (IF). Cbl is freed from R factors in the duodenum by proteolytic digestion of the R factors by pancreatic enzymes. The IF-Cbl complex transits to the ileum where it is bound to ileal receptors. The IF-Cbl enters the ileal absorptive cell, and the Cbl is released and enters the plasma. In the plasma, the Cbl is bound to transcobalamin II (TC II), which delivers the complex to nonintestinal cells. In these cells, Cbl is freed from the transport protein.
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In adults, pernicious anemia is associated with severe gastric atrophy and achlorhydria, which are irreversible. Coexistent iron deficiency is common because achlorhydria prevents solubilization of dietary ferric iron from foodstuffs. Autoimmune phenomena and thyroid disease frequently are observed. Patients with pernicious anemia have a 2- to 3-fold increased incidence of gastric carcinoma.
In your Case Study Analysis related to the scenario provided, explain the following as it applies to the scenario you were provided (not all may apply to each scenario):
The factors that affect fertility (STDs).
Why inflammatory markers rise in STD/PID.
Why prostatitis and infection happens. Also explain the causes of systemic reaction.
Why a patient would need a splenectomy after a diagnosis of ITP.
Anemia and the different kinds of anemia (i.e., micro and macrocytic).
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Rubric
Excellent Good Fair Poor
Develop a 1- to 2-page case study analysis, examining the patient symptoms presented in the case study. Be sure to address the following as it relates to the case you were assigned (omit section that does not pertain to your case, faculty will give full points for that section):
Explain the factors that affect fertility (STDs) 23 (23%) – 25 (25%)
The response accurately and thoroughly describes the patient symptoms.
The response includes accurate, clear, and detailed explanations of the processes related to women\’s and men\’s health, infections, and hematologic disorders and is supported by evidence and/or research, as appropriate, to support the explanation. 20 (20%) – 22 (22%)
The response describes the patient symptoms.
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The response includes accurate, explanations of the processes related to women\’s and men\’s health, infections, and hematologic disorders and is supported by evidence and/or research, as appropriate, to support the explanation. 18 (18%) – 19 (19%)
The response describes the patient symptoms in a manner that is vague or inaccurate.
The response includes explanations of the processes related to women\’s and men\’s health, infections, and hematologic disorders, with explanations that are vague or based on inappropriate evidence/research. 0 (0%) – 17 (17%)
The response describes the patient symptoms in a manner that is vague and inaccurate, or the description is missing.
The response does not include explanations of the processes related to women\’s and men\’s health, infections, and hematologic disorders, or the explanations are vague or based on inappropriate evidence/research.
Explain why inflammatory markers rise in STD/PID 18 (18%) – 20 (20%)
The response includes an accurate, complete, detailed, and specific analysis of the concepts and principles of pathophysiology across the life span and is supported by evidence and/or research, as appropriate, to support the explanation. 16 (16%) – 17 (17%)
The response includes an accurate explanation of how the highlighted processes interact to affect the patient and is supported by evidence and/or research, as appropriate, to support the explanation. 14 (14%) – 15 (15%)
The response includes a vague or inaccurate explanation of how the highlighted processes interact to affect the patient, with explanations that are based on inappropriate evidence/research. 0 (0%) – 13 (13%)
The response includes a vague or inaccurate explanation of how the highlighted processes interact to affect the patient, with explanations that are based on inappropriate or missing evidence/research.
Explain why prostatitis and infection happen. Also explain the causes of systemic reaction. 18 (18%) – 20 (20%)
The response includes an accurate, complete, detailed, and specific explanation of how the highlighted processes interact to affect the patient and is supported by evidence and/or research, as appropriate, to support the explanation. 16 (16%) – 17 (17%)
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The response includes an accurate explanation of how the highlighted processes interact to affect the patient and is supported by evidence and/or research, as appropriate, to support the explanation. 14 (14%) – 15 (15%)
The response includes a vague or inaccurate explanation of how the highlighted processes interact to affect the patient, with explanations that are based on inappropriate evidence/research. 0 (0%) – 13 (13%)
The response includes a vague or inaccurate explanation of how the highlighted processes interact to affect the patient, with explanations that are based on inappropriate or missing evidence/research.
Explain why a patient would need a splenectomy after a diagnosis of ITP. 5 (5%) – 10 (10%)
The response includes an accurate, complete, detailed, and specific explanation of racial/ethnic variables that may impact physiological functioning and is supported by evidence and/or research, as appropriate, to support the explanation. 4 (4%) – 4 (4%)
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The response includes an accurate explanation of racial/ethnic variables that may impact physiological functioning and is supported by evidence and/or research, as appropriate, to support the explanation. 3 (3%) – 3 (3%)
The response includes a vague or inaccurate explanation of racial/ethnic variables that may impact physiological functioning, and/or explanations are based on inappropriate evidence/research. 0 (0%) – 2 (2%)
The response includes a vague or inaccurate explanation of racial/ethnic variables that may impact physiological functioning, or the explanations are based on inappropriate or no evidence/research.
Explain anemia and the different kinds of anemia (i.e., micro and macrocytic). 5 (5%) – 10 (10%)
The response includes an accurate, complete, detailed, and specific explanation of racial/ethnic variables that may impact physiological functioning and is supported by evidence and/or research, as appropriate, to support the explanation. 4 (4%) – 4 (4%)
The response includes an accurate explanation of racial/ethnic variables that may impact physiological functioning and is supported by evidence and/or research, as appropriate, to support the explanation. 3 (3%) – 3 (3%)
The response includes a vague or inaccurate explanation of racial/ethnic variables that may impact physiological functioning, and/or explanations are based on inappropriate evidence/research. 0 (0%) – 2 (2%)
The response includes a vague or inaccurate explanation of racial/ethnic variables that may impact physiological functioning, or the explanations are based on inappropriate or no evidence/research.
Written Expression and Formatting – Paragraph Development and Organization:
Paragraphs make clear points that support well-developed ideas, flow logically, and demonstrate continuity of ideas. Sentences are carefully focused—neither long and rambling nor short and lacking substance.
A clear and comprehensive purpose statement and introduction are provided that delineate all required criteria. 5 (5%) – 5 (5%)
Paragraphs and sentences follow writing standards for flow, continuity, and clarity.
A clear and comprehensive purpose statement, introduction, and conclusion are provided that delineate all required criteria. 4 (4%) – 4 (4%)
Paragraphs and sentences follow writing standards for flow, continuity, and clarity 80% of the time.
The purpose, introduction, and conclusion of the assignment are stated, yet are brief and not descriptive. 3 (3%) – 3 (3%)
Paragraphs and sentences follow writing standards for flow, continuity, and clarity 60%-79% of the time.
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The purpose, introduction, and conclusion of the assignment are vague or off topic. 0 (0%) – 2 (2%)
Paragraphs and sentences follow writing standards for flow, continuity, and clarity < 60% of the time.
No purpose statement, introduction, or conclusion were provided.
Written Expression and Formatting – English Writing Standards:
Correct grammar, mechanics, and proper punctuation 5 (5%) – 5 (5%)
Uses correct grammar, spelling, and punctuation with no errors. 4 (4%) – 4 (4%)
Contains a few (1 or 2) grammar, spelling, and punctuation errors. 3 (3%) – 3 (3%)
Contains several (3 or 4) grammar, spelling, and punctuation errors. 0 (0%) – 2 (2%)
Contains many (≥ 5) grammar, spelling, and punctuation errors that interfere with the reader\’s understanding.
Written Expression and Formatting – The paper follows correct APA format for title page, headings, font, spacing, margins, indentations, page numbers, running heads, parenthetical/in-text citations, and reference list. 5 (5%) – 5 (5%)
Uses correct APA format with no errors.
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Ferritin is what’s known as an acute phase reactant. This means that when the body experiences inflammation, ferritin levels will go up. That’s why ferritin levels can be high in people who have liver disease or types of cancer, such as Hodgkin’s lymphoma.
For example, liver cells have stored ferritin. When a person’s liver is damaged, the ferritin inside the cells begins to leak out. A doctor would expect higher than normal ferritin levels in people with these and other inflammatory conditions.
SAMPLE SOLUTION
Factors that affect fertility (STDs)
STDs can affect fertility if left untreated. This occurs when the STDs spread to the fallopian tube or the uterus to cause pelvic inflammatory disease. This condition causes inflammation, scarring, and blockage of the reproductive organs such as the fallopian tubes. Scarring of the tubes can cause blockage thus preventing eggs from moving to the uterus. Some STDs such as chlamydia may also cause low sperm count in males thereby affecting their fertility (Low & Broutet, 2017).
Why Inflammatory Markers Rise in STD/PID. STD/PID infections affect the female genital tract by causing inflammation. If left untreated, PID causes the scarring of tissues in the…
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