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Pathology - Iron Deficiency Anemia
Iron-deficiency anemia is most likely linked to GI hemorrhage. Iron-deficiency anemia is the most common anemia, typically due to loss of iron from chronic bleeding; however, decreased intake, increased utilization (pregnant women, infants), malabsorptive disorders (celiac’s disease), and some hemoglobinopathies (paroxysmal nocturnal hemoglobinuria) can also be causative. As iron reserves drop, so does serum ferritin (which is the protein bound physiologically accessible form of iron). The TIBC of transferrin increases to maximize use of available iron; nevertheless, the fraction of saturated binding sites decreases due to shortage of available iron. In summary, test data demonstrate decreased serum iron, ferritin, and hemoglobin saturation with increased TIBC. Any unexplained iron-deficiency anemia in an older patient (postmenopausal woman) with a positive FOBT should trigger a colonoscopy to rule-out colon cancer. TSH is tested to rule-out hypothyroidism and liver function tests to screen for harmful side effects of simvastatin as causes of the patient’s presenting problems.
Iron-deficiency anemia is most likely linked to GI hemorrhage. Iron-deficiency anemia is the most common anemia, typically due to loss of iron from chronic bleeding; however, decreased intake, increased utilization (pregnant women, infants), malabsorptive disorders (celiac’s disease), and some hemoglobinopathies (paroxysmal nocturnal hemoglobinuria) can also be causative. As iron reserves drop, so does serum ferritin (which is the protein bound physiologically accessible form of iron). The TIBC of transferrin increases to maximize use of available iron; nevertheless, the fraction of saturated binding sites decreases due to shortage of available iron. In summary, test data demonstrate decreased serum iron, ferritin, and hemoglobin saturation with increased TIBC. Any unexplained iron-deficiency anemia in an older patient (postmenopausal woman) with a positive FOBT should trigger a colonoscopy to rule-out colon cancer. TSH is tested to rule-out hypothyroidism and liver function tests to screen for harmful side effects of simvastatin as causes of the patient’s presenting problems.
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Pathology - α-thalassemia trait
α-thalassemia trait (minor), a disease of α-chain synthesis more typically reported in African American and southeastern Asian cultures. In this variation, two α-chain deletions exist. In African Americans, the losses are on separate chromosomes (α/- α/-), but the losses are on the same chromosome (-/- α/α) in Asians. The lack of two chains results in a global drop in all normal adult hemoglobin synthesis (HbA, HbA 2 , HbF); consequently, the electrophoresis is normal (relative quantities are the same as all hemoglobin types require the α-chain and are equally affected). With normal ferritin, the diagnosis is made by microcytic anemia and an elevated erythrocyte count, which is peculiar to thalassemias in anemias. Teardrop erythrocytes are a result of membrane damage due to removal of excess globin. Other α-thalassemias result from deletion of one, three, and four α-chains. One deletion produces an asymptomatic carrier without anemia. Three deletions generate hemoglobin H (HbH) illness, which produces a severe hemolytic anemia with HbH (four β-chains) identifiable by electrophoresis. Four deletions resulted in hemoglobin Bart (four γ-chains) illness, which creates hydrops fetalis in utero and is incompatible with life.
α-thalassemia trait (minor), a disease of α-chain synthesis more typically reported in African American and southeastern Asian cultures. In this variation, two α-chain deletions exist. In African Americans, the losses are on separate chromosomes (α/- α/-), but the losses are on the same chromosome (-/- α/α) in Asians. The lack of two chains results in a global drop in all normal adult hemoglobin synthesis (HbA, HbA 2 , HbF); consequently, the electrophoresis is normal (relative quantities are the same as all hemoglobin types require the α-chain and are equally affected). With normal ferritin, the diagnosis is made by microcytic anemia and an elevated erythrocyte count, which is peculiar to thalassemias in anemias. Teardrop erythrocytes are a result of membrane damage due to removal of excess globin. Other α-thalassemias result from deletion of one, three, and four α-chains. One deletion produces an asymptomatic carrier without anemia. Three deletions generate hemoglobin H (HbH) illness, which produces a severe hemolytic anemia with HbH (four β-chains) identifiable by electrophoresis. Four deletions resulted in hemoglobin Bart (four γ-chains) illness, which creates hydrops fetalis in utero and is incompatible with life.
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Pathology - β-thalassemia major
β-thalassemia major is established by the lack of HbA 1 (composed of α-2 and β-2) on electrophoresis.
In contrast to heterozygous β-thalassemia minor, the patient is homozygous for deletion of the β-hemoglobin gene.
Therefore, absence of β-chain synthesis enhances production of HbA 2 (α-2, δ-2) and HbF (α-2, γ-2). The anemia is a result of inefficient erythropoiesis; nevertheless, breakdown products of excess α-chains also results in intramedullary destruction of RBC precursors and peripheral hemolysis. The overall loss in hemoglobin results in a microcytic, hypochromic anemia. Resulting tissue hypoxia drives EPO production, which causes marrow growth and bone deformity, as evidenced by the hypertrophied mandible of this infant. Increased iron absorption from marrow expansion coupled with transfusion-dependent survival often results in heart failure owing to hemochromatosis.
Patients with β-thalassemia minor are largely asymptomatic unless rarely during pregnancy.
β-thalassemia major is established by the lack of HbA 1 (composed of α-2 and β-2) on electrophoresis.
In contrast to heterozygous β-thalassemia minor, the patient is homozygous for deletion of the β-hemoglobin gene.
Therefore, absence of β-chain synthesis enhances production of HbA 2 (α-2, δ-2) and HbF (α-2, γ-2). The anemia is a result of inefficient erythropoiesis; nevertheless, breakdown products of excess α-chains also results in intramedullary destruction of RBC precursors and peripheral hemolysis. The overall loss in hemoglobin results in a microcytic, hypochromic anemia. Resulting tissue hypoxia drives EPO production, which causes marrow growth and bone deformity, as evidenced by the hypertrophied mandible of this infant. Increased iron absorption from marrow expansion coupled with transfusion-dependent survival often results in heart failure owing to hemochromatosis.
Patients with β-thalassemia minor are largely asymptomatic unless rarely during pregnancy.
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Pathology - Tetanus
A highly infected wound may requires tetanus treatment. A highly contaminated wound with no history of tetanus vaccine requires tetanus and diphtheria (Td) toxoid as well as tetanus immune globulin (TIG).
Previously immunized patients do not require TIG and only require the Td toxoid if it has been greater than 5 years since their last immunization. Clean, mild wounds require Td toxoid only for unvaccinated patients (or patients with incomplete vaccination series) or those who have greater than 10 years since their last vaccine. TIG is not typically given for clean, small wounds.
A highly infected wound may requires tetanus treatment. A highly contaminated wound with no history of tetanus vaccine requires tetanus and diphtheria (Td) toxoid as well as tetanus immune globulin (TIG).
Previously immunized patients do not require TIG and only require the Td toxoid if it has been greater than 5 years since their last immunization. Clean, mild wounds require Td toxoid only for unvaccinated patients (or patients with incomplete vaccination series) or those who have greater than 10 years since their last vaccine. TIG is not typically given for clean, small wounds.
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Pathology - Pneumococcal Conjugate Vaccine in Sickle-Cell Disease
This patient may has functional asplenia secondary to splenic infarct from sickle-cell anemia. The objective of vignettes like this is to recognize what preventative measures are appropriate for certain patient groups. Patients with functional or surgical asplenia are at higher sensitivity to encapsulated pathogens such as pneumococcus. Although this patient should have had the pneumococcal conjugated vaccination, it is suggested that patients with asplenia additionally obtain the pneumococcal polysaccharide vaccine due to its extended number of serotypes covered. It is important to highlight that this patient is also sensitive to organisms such as Neisseria and Haemophilus . This patient should additionally receive the meningococcal and Haemophilus influenzae B vaccines if he has not already.
This patient may has functional asplenia secondary to splenic infarct from sickle-cell anemia. The objective of vignettes like this is to recognize what preventative measures are appropriate for certain patient groups. Patients with functional or surgical asplenia are at higher sensitivity to encapsulated pathogens such as pneumococcus. Although this patient should have had the pneumococcal conjugated vaccination, it is suggested that patients with asplenia additionally obtain the pneumococcal polysaccharide vaccine due to its extended number of serotypes covered. It is important to highlight that this patient is also sensitive to organisms such as Neisseria and Haemophilus . This patient should additionally receive the meningococcal and Haemophilus influenzae B vaccines if he has not already.
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Pathology - Hyperacute Rejection of Transplant
This irreversible type II hypersensitivity reaction of preformed recipient alloantibodies to either the ABO blood group or HLA class I antigens on the graft endothelium occurs within minutes to maybe hours. The binding of the antibodies promotes release of particles that promote coagulation and cytokines that recruit inflammatory mediators. The graft tissue is destroyed through vascular thrombosis and rapid organ death as described in this patient. It is now rare due to good ABO screening and HLA crossmatching.
Patients who are most prone to have this occur are often listed with the highest priority for a graft. Preformed antibodies may result from many transfusions, several pregnancies, or prior transplants.
This irreversible type II hypersensitivity reaction of preformed recipient alloantibodies to either the ABO blood group or HLA class I antigens on the graft endothelium occurs within minutes to maybe hours. The binding of the antibodies promotes release of particles that promote coagulation and cytokines that recruit inflammatory mediators. The graft tissue is destroyed through vascular thrombosis and rapid organ death as described in this patient. It is now rare due to good ABO screening and HLA crossmatching.
Patients who are most prone to have this occur are often listed with the highest priority for a graft. Preformed antibodies may result from many transfusions, several pregnancies, or prior transplants.
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Pathology - Graft Versus Host Disease
This reaction is a potential complication in bone marrow and liver transplants and is the result of T lymphocytes from donor transplant product perceiving the host tissues as foreign. The responding donor T cells activate CD4 + and CD8 + T cells in the host, inducing lymphocytic infiltration of the skin, GI tract, and liver. Damage to these organs creates the distinctive clinical signs including dermatitis, crampy stomach pain with bloody diarrhea and/or anorexia, cholestasis producing jaundice and probably hepatocellular necrosis, as well as fever. Severity of symptoms predicts mortality. The reaction may occur in days to weeks following transplant. Posttransplant immunosuppression and ways to eliminate T cells from donor tissue has lowered the incidence, although it is still relatively common. The conventional treatment consists of injectable glucocorticoids, which require careful tapering.
This reaction is a potential complication in bone marrow and liver transplants and is the result of T lymphocytes from donor transplant product perceiving the host tissues as foreign. The responding donor T cells activate CD4 + and CD8 + T cells in the host, inducing lymphocytic infiltration of the skin, GI tract, and liver. Damage to these organs creates the distinctive clinical signs including dermatitis, crampy stomach pain with bloody diarrhea and/or anorexia, cholestasis producing jaundice and probably hepatocellular necrosis, as well as fever. Severity of symptoms predicts mortality. The reaction may occur in days to weeks following transplant. Posttransplant immunosuppression and ways to eliminate T cells from donor tissue has lowered the incidence, although it is still relatively common. The conventional treatment consists of injectable glucocorticoids, which require careful tapering.
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Pathology - DiGeorge Syndrome
congenital thymic aplasia is more often known as DiGeorge syndrome. The condition originates from a failure of the third and fourth pharyngeal pouches to form, resulting in absence of the thymus and parathyroid glands. CATCH-22 is a famous mnemonic used to memorize the clinical signs of the condition. The primary findings are connected to C ardiac defects, as suggested by this patient’s typical ventricular septal defect murmur, as well as A bnormal midline features, including the facial traits mentioned in this patient. Failure of T hymic development results in absence of T cells and susceptibility to opportunistic pathogens, particularly P. jirovecii . C left palate is also a common finding. The lack of PTH can generate symptomatic H ypocalcemia and tetany, as evidenced by the positive Trousseau’s sign (carpal and phalangeal spasm) when the blood pressure cuff is inflated on the patient. The normal genetic mutation is not inherited, but rather a random deletion of the long arm on chromosome 22 (22q11.2 deletion). Live vaccines (e.g., measles, small pox, varicella) are contraindicated. Presentation can be as severe as those of SCID. Therapy involves antimicrobial prophylaxis and thymic transplantation, however the risk of graft-versus-host disease (GVHD) is substantial.
congenital thymic aplasia is more often known as DiGeorge syndrome. The condition originates from a failure of the third and fourth pharyngeal pouches to form, resulting in absence of the thymus and parathyroid glands. CATCH-22 is a famous mnemonic used to memorize the clinical signs of the condition. The primary findings are connected to C ardiac defects, as suggested by this patient’s typical ventricular septal defect murmur, as well as A bnormal midline features, including the facial traits mentioned in this patient. Failure of T hymic development results in absence of T cells and susceptibility to opportunistic pathogens, particularly P. jirovecii . C left palate is also a common finding. The lack of PTH can generate symptomatic H ypocalcemia and tetany, as evidenced by the positive Trousseau’s sign (carpal and phalangeal spasm) when the blood pressure cuff is inflated on the patient. The normal genetic mutation is not inherited, but rather a random deletion of the long arm on chromosome 22 (22q11.2 deletion). Live vaccines (e.g., measles, small pox, varicella) are contraindicated. Presentation can be as severe as those of SCID. Therapy involves antimicrobial prophylaxis and thymic transplantation, however the risk of graft-versus-host disease (GVHD) is substantial.
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Pathology - Ataxia Telangiectasia Syndrome
Ataxia-telangiectasia syndrome is an autosomal recessive disorder stemming from a deficiency in DNA damage repair. Specifically, the ataxia-telangiectasia gene (ATM) is mutated. This gene encodes a protein, which normally serves as a regulator of cell-cycle checkpoints to give time for repair of double-stranded DNA breaks.
This abnormality results in deficient cellular immunity and humoral immunodeficiency with thymic hypoplasia due to the fragile chromosomes that are created within the cells. Instability of the chromosomes also puts patients at increased risk for lymphomas and leukemias. Patients will typically present after the first year of life, when they will be delayed in walking secondary to ataxia. The ataxia occurs subsequent to atrophy of the cerebellum, which normally functions to coordinate balance (in conjunction with the vestibular system) and fine motor control. Oculomotor apraxia, which is difficulties with coordinated head and eye movements, can appear as an inability to track objects in young children. Speech will likely also fail to develop adequately. Patients will exhibit characteristic ocular and cutaneous telangiectasias, which are dilated blood vessels. In addition to decreased IgE and IgA, they also interestingly have raised serum alpha-fetoprotein. Patients with Friedrich’s ataxia, which can present similarly, can be separated from ataxia-telangiectasia syndrome because those patients will not have signs of oculomotor apraxia or the immunologic abnormalities.
Ataxia-telangiectasia syndrome is an autosomal recessive disorder stemming from a deficiency in DNA damage repair. Specifically, the ataxia-telangiectasia gene (ATM) is mutated. This gene encodes a protein, which normally serves as a regulator of cell-cycle checkpoints to give time for repair of double-stranded DNA breaks.
This abnormality results in deficient cellular immunity and humoral immunodeficiency with thymic hypoplasia due to the fragile chromosomes that are created within the cells. Instability of the chromosomes also puts patients at increased risk for lymphomas and leukemias. Patients will typically present after the first year of life, when they will be delayed in walking secondary to ataxia. The ataxia occurs subsequent to atrophy of the cerebellum, which normally functions to coordinate balance (in conjunction with the vestibular system) and fine motor control. Oculomotor apraxia, which is difficulties with coordinated head and eye movements, can appear as an inability to track objects in young children. Speech will likely also fail to develop adequately. Patients will exhibit characteristic ocular and cutaneous telangiectasias, which are dilated blood vessels. In addition to decreased IgE and IgA, they also interestingly have raised serum alpha-fetoprotein. Patients with Friedrich’s ataxia, which can present similarly, can be separated from ataxia-telangiectasia syndrome because those patients will not have signs of oculomotor apraxia or the immunologic abnormalities.
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Pathology - Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) is an X-linked recessive condition. Like with other autoimmune disorders, the sorts of microorganisms that infect the patient hint to the deficiency in the immune response. A patient with CGD will have recurrent infections from fungus and staphylococcus (gram-positive cocci in clusters). The deficiency in CGD is inadequate nicotine adenine dinucleotide phosphate oxidase in neutrophil and monocyte cell membranes, resulting to suppressed superoxide dismutase activity and lowered hydrogen peroxide levels. This limits free-radical generation and resulting in an absence respiratory burst, such that phagocytized catalase-positive bacteria are not destroyed. The diagnosis of CGD can be made by the laboratory observation of neutrophils and macrophages failing to decrease a nitroblue tetrazolium dye (leukocytes with an intact respiratory burst create a blue color upon incubation). Myeloperoxidase deficiency, which is a more common abnormality, is characterized by a normal respiratory burst but absence of hypochlorous acid (bleach) synthesis. The only clinical importance, however, shows in vulnerable patients with DM through significant candidal infections.
Chronic granulomatous disease (CGD) is an X-linked recessive condition. Like with other autoimmune disorders, the sorts of microorganisms that infect the patient hint to the deficiency in the immune response. A patient with CGD will have recurrent infections from fungus and staphylococcus (gram-positive cocci in clusters). The deficiency in CGD is inadequate nicotine adenine dinucleotide phosphate oxidase in neutrophil and monocyte cell membranes, resulting to suppressed superoxide dismutase activity and lowered hydrogen peroxide levels. This limits free-radical generation and resulting in an absence respiratory burst, such that phagocytized catalase-positive bacteria are not destroyed. The diagnosis of CGD can be made by the laboratory observation of neutrophils and macrophages failing to decrease a nitroblue tetrazolium dye (leukocytes with an intact respiratory burst create a blue color upon incubation). Myeloperoxidase deficiency, which is a more common abnormality, is characterized by a normal respiratory burst but absence of hypochlorous acid (bleach) synthesis. The only clinical importance, however, shows in vulnerable patients with DM through significant candidal infections.
