Case Study - Patient Diagnosis
redginger28
Chapter_023.pptxChapter 23
Alterations in Hematologic Function
Anemia (1 of 4)
Reduction in the total number of erythrocytes in the circulating blood or in the quality or quantity of hemoglobin
Impaired erythrocyte production
Acute or chronic blood loss
Increased erythrocyte destruction
Combination of the above
Anemia (2 of 4)
Classifications by size and hemoglobin
Size
Identified by terms that end in -cytic
Macrocytic, microcytic, normocytic
Hemoglobin content
Identified by terms that end in -chromic
Normochromic and hypochromic
Anemia (3 of 4)
Anisocytosis
Red cells are present in various sizes
Poikilocytosis
Red cells are present in various shapes
Anemia (4 of 4)
Physiologic manifestation
Reduced oxygen-carrying capacity—hypoxemia
Variable symptoms based on severity and the ability of the body to compensate
Classic anemia symptoms:
Fatigue
Weakness
Dyspnea
Pallor
Anemias of Blood Loss
Acute blood loss
Posthemorrhagic anemia
Normocytic-normochromic anemia
Effects depend on rate of hemmorhage
Often due to trauma
Chronic blood loss
Anemia occurs if loss is greater than replacement capacity of bone marrow
Iron deficiency anemia can occur
Macrocytic Anemias (1 of 3)
Also termed megaloblastic anemias
Characterized by unusually large stem cells
Erythrocytes are large in size, thickness, volume
Result of defective DNA synthesis
Caused by deficiencies in vitamin B12 or folate
Ribonucleic acid (RNA) processes occur at a normal rate
Overproduction of hemoglobin
Macrocytic Anemias (2 of 3)
Pernicious anemia
Caused by a lack of intrinsic factor from the gastric parietal cells
Required for vitamin B12 absorption
Results in vitamin B12 deficiency
Manifestations
Early symptoms nonspecific and vague
When hemoglobin at 7-8 g/dl:
Weakness, fatigue, difficulty walking, paresthesias, loss of appetite, abdominal pain, weight loss, sore tongue
Neurologic manifestations
Treatment is life-long B12 replacement
Macrocytic Anemias (3 of 3)
Folate deficiency anemia
Humans dependent on dietary intake of folate
Absorption of folate occurs in the upper small intestine
Not dependent on any other factor
Similar symptoms to pernicious anemia except neurologic manifestations generally not seen
Treatment requires daily oral administration of folate body levels are adequate
Microcytic-Hypochromic Anemias (1 of 3)
Characterized by red cells that are abnormally small and contain reduced amounts of hemoglobin
Microcytic-Hypochromic Anemias (2 of 3)
Iron deficiency anemia
Most common nutritional disorder worldwide
Causes:
Dietary deficiency
Impaired absorption
Increased requirement
Chronic blood loss
Chronic diarrhea
Microcytic-Hypochromic Anemias (3 of 3)
Iron deficiency anemia
Manifestations when serum Hgb decreased to 7 or 8 per/dL
Early symptoms are nonspecific: fatigue; weakness; shortness of breath; pale earlobes, palms, and conjunctiva
Progression of iron deficiency causes:
Brittle, thin, coarsely ridged, and spoon-shaped nails (koilonychia)
Cheilosis, stomatitis, painful ulcerations in mouth
Dysphasia
Anemia of Chronic Disease (1 of 2)
Also called anemia of inflammation
Decreased erythropoiesis and impaired iron utilization in chronic disease or inflammation
Common in hospitalized patients
Results from:
Decreased erythrocyte life span
Suppressed production of erythropoietin
Ineffective bone marrow response
Altered iron metabolism in macrophages
Anemia of Chronic Disease (2 of 2)
Initially normocytic-normochromic, becomes microcytic-hypochromic
Treatment is aimed at underlying disorder
If inflammatory/infectious conditions are not found, patient is screened for malignancies
Aplastic and Hemolytic Anemias
Aplastic anemia
Hematopoietic failure or bone marrow aplasia
Reduced production of mature cells
Pancytopenia
Hemolytic anemia
Premature accelerated destruction of erythrocytes
Myeloproliferative RBC Disorders (1 of 4)
Polycythemia
Overproduction of red blood cells
Relative polycythemia
Hemoconcentration of blood due to dehydration
Fluid loss results in relative increases of red cell counts and Hgb and Hct values
Myeloproliferative RBC Disorders (2 of 4)
Absolute polycythemia
Primary
Polycythemia vera (PV)
Secondary
Increase in erythropoietin as a normal response to chronic hypoxia or an inappropriate response to erythropoietin-secreting tumors
Myeloproliferative RBC Disorders (3 of 4)
Polycythemia vera (primary polycythemia)
Blood cancer in which bone marrow makes too many RBCs
WBCs and platelets are also often increased
Acquired mutation in JAK2 gene
Uncommon and insidious
Manifestations due to increased red cell mass and hematocrit
Increased blood volume and viscosity
Hypercoagulopathy
Myeloproliferative RBC Disorders (4 of 4)
Hereditary hemochromatosis
Iron overload disorder
Autosomal recessive disorder of iron metabolism
Mutations in one of several genes: HFE, HJV, HAMP, FR2, SLC40A1
Hepcidin—protein that governs iron regulation
Mutations impair control of iron absorption
Manifestations from excessive storage of iron in liver, skin, pancreas, heart, joints, and testes
Abdominal pain, weakness, weight loss
Cirrhosis
Question 1
Which of the following is characteristic of the megaloblastic anemias?
Small cell size
Decreased thickness
Presence of macrocytes
Caused by increased folate
Note: No input needed to proceed
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Question 1 Answer
Correct Answer: C
There are macrocytes that are unusually large stem cells (megaloblasts) in the marrow that mature into unusually large stem cells (macrocytes) in the circulation. There are increases in size, thickness, and volume with these cells. Deficiencies of vitamin B12 or folate cause these anemias.
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Alterations of Leukocyte Function
Quantitative disorders
Increases or decreases in cell numbers
Bone marrow disorders or premature destruction of cells
Response to infectious microorganism invasion
Qualitative disorders
Disruptions of leukocyte function
Phagocytes or lymphocytes lose abilities
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Quantitative Alterations of Leukocytes
Leukocytosis
High leukocyte count
Leukocytosis is a normal protective physiologic response to physiologic stressors, such as infectious microorganisms
Leukopenia
Low leukocyte count
Leukopenia is not normal and not beneficial
Predisposes a patient to infections
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Quantitative Alterations of Granulocytes (1 of 4)
Granulocytosis (neutrophilia)
Increase in granulocytes
Neutrophilia is evident in the first stages of an infection or inflammation
If the need for neutrophils increases beyond the supply, immature neutrophils are released
Phenomenon is termed shift-to-the-left
When the population returns to normal: shift-to-the-right
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Quantitative Alterations of Granulocytes (2 of 4)
Neutropenia
Reduction in circulating neutrophils
Causes:
Prolonged severe infection
Decreased production
Reduced survival
Abnormal neutrophil distribution and sequestration
Granulocytopenia (severe neutropenia) and agranulocytosis (absence of granulocytes)
Chemotherapy
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Quantitative Alterations of Granulocytes (3 of 4)
Eosinophilia
Increase in circulating eosinophils
Triggered by hypersensitivity reactions
Allergic disorders and parasitic invasions
Eosinopenia
Decrease in circulation numbers of eosinophils
Caused by migration of cells to inflammatory sites
Other causes include Cushing syndrome and stress from surgery, shock, trauma, or mental distress
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Quantitative Alterations of Granulocytes (4 of 4)
Basophilia
Increase in circulating basophils
Response to inflammation and hypersensitivity reactions
Seen in myeloproliferative disorders
Basopenia
Decrease in circulating numbers of basophils
Occurs in acute infections, hyperthyroidism, ovulation and pregnancy, and long-term steroid therapy
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Quantitative Alterations of Monocytes
Monocytosis
Increase in circulating monocytes
Often transient and unrelated to dysfunction of monocyte production
Usually occurs with neutropenia in later stages of infections when monocytes are needed to phagocytize organisms and debris
Monocytopenia
Decrease in circulating monocytes
Very rare
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Quantitative Alterations of Lymphocytes
Lymphocytosis
Increase in number or proportion of lymphocytes
Caused by acute viral infections, particularly caused by Epstein-Barr virus (EBV)
Lymphocytopenia
Decrease in the number of circulating lymphocytes
Causes:
Abnormal production due to immune deficiencies
Destruction by drugs, viruses, or radiation
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Question 2
Which of the following terms best describes a higher-than-normal white blood cell count?
Neutrophilia
Leukopenia
Leukocytosis
Granulocytosis
Note: No input needed to proceed
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Question 2 Answer
Correct Answer: C
Leukocytosis is an increase in the number of leukocytes or white blood cells in the blood. The decrease in number of white blood cells is termed leukopenia. Granulocytosis is an increase in the number of granulocytes in the blood. The neutrophil is the most numerous of the granulocytes and the term granulocytosis is often used in place of neutrophilia.
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Infectious Mononucleosis (1 of 3)
Benign, acute, self-limiting infection of B lymphocytes transmitted by saliva through personal contact
Most common cause is EBV
Others viruses that cause similar symptoms:
Cytomegalovirus (CMV)
Hepatitis
Influenza
HIV
Rubella
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Infectious Mononucleosis (2 of 3)
Symptoms at time of diagnosis:
Fever
Fatigue
Sore throat
Swollen cervical lymph nodes
Increased lymphocyte count
Atypical (activated) lymphocytes
Serious complications are rare
Splenic rupture is most common cause of death
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Infectious Mononucleosis (3 of 3)
Diagnosis
>50% lymphocytes and at least 10% atypical lymphocytes
Monospot qualitative test for heterophilic antibodies
Antibodies for EBV antigens
Treatment is supportive and treats the symptoms
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Leukemias (Lymphoid Neoplasms) (1 of 2)
Malignant disorder of the bone marrow and blood
Excessive accumulation of leukemic cells
Cells crowd bone marrow
Decreased function of hematopoietic cells
Pancytopenia
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Leukemias (Lymphoid Neoplasms) (2 of 2)
Acute leukemia
Presence of undifferentiated or immature cells, usually blast cells
Onset abrupt and rapid
Without treatment, short survival time
Chronic leukemia
Predominant cell is mature but does not function normally
Slow progression
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Acute Leukemias
Acute lymphocytic leukemia (ALL)
Too many lymphoblasts
Mostly occurs in children
Acute myelogenous leukemia (AML)
Too many myeloblasts
Most common adult leukemia
Bone marrow depression causes signs/symptoms: fatigue, bleeding, fever, anorexia, and neurologic symptoms
Treated with chemotherapy
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Chronic Leukemias
Chronic myelogenous leukemia (CML)
Too many blood cells made in bone marrow
Treatment is chemotherapy, biologic response modifiers, and stem cell transplant
Chronic lymphocytic leukemia (CLL)
Too many immature lymphocytes
Most common adult leukemia in western world
Treatment is observation with symptom treatment
Slow progression
Lymphadenopathy
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Alterations in Lymphoid Function
Alterations include:
Lymphadenopathy
Malignant lymphomas
Plasma cell malignancy
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Lymphadenopathy (1 of 2)
Enlarged lymph nodes that become palpable and tender
Localized lymphadenopathy
Drainage of an inflammatory lesion located near the enlarged node
Generalized lymphadenopathy
Occurs in the presence of infections, autoimmune diseases, or disseminated malignancy
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Lymphadenopathy (2 of 2)
Courtesy Dr. A.R. Kagan, Los Angeles. From del Regato JA et al: Cancer: diagnosis, treatment, and prognosis, ed 6, St Louis, 1985, Mosby.
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Malignant Lymphomas
Diverse group of neoplasms that develop from the proliferation of malignant lymphocytes in the lymphoid system
Most common blood cancer in US
REAL classification
Hodgkin lymphoma
Non-Hodgkin lymphoma
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Hodgkin Lymphoma (1 of 4)
Malignant, progresses from one group of lymph nodes to another
Systemic symptoms
Presence of Reed-Sternberg (RS) cells
RS cells are malignant transformed lymphocytes
Necessary for diagnosis, but not specific to Hodgkin lymphoma
Types:
Classic Hodgkin
Nodular lymphocyte-predominant Hodgkin
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Hodgkin Lymphoma (2 of 4)
Reed-Sternberg cells
From Damjanov I, Linder J, editors, Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
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Hodgkin Lymphoma (3 of 4)
Physical findings
Enlarged painless lymph node in neck, mediastinal mass, splenomegaly
Symptoms
Fever, weight loss, night sweats, pruritus
Adult Hodgkin lymphoma can usually be cured with early diagnosis and treatment
Chemotherapy
Radiation
Surgery
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Hodgkin Lymphoma (4 of 4)
From del Regato JA et al: Cancer: diagnosis, treatment, and prognosis, ed 6, St Louis, 1985, Mosby.
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Non-Hodgkin Lymphoma (1 of 3)
Generic term for a diverse group of lymphoid tissue neoplasms
REAL classification
B-cell neoplasms
T-cell and NK-cell neoplasms
Burkitt lymphoma
Lymphoblastic lymphoma
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Non-Hodgkin Lymphoma (2 of 3)
Risk factors include being older, male, or white, plus having one of the following:
Certain immune disorders, autoimmune disease, or HIV/AIDS
Exposure to mutagenic chemicals
Infection with certain cancer related viruses
Immune suppression related to organ transplantation
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Non-Hodgkin Lymphoma (3 of 3)
Progressive clonal expansion of B cells, T cells, and/or NK cells
Oncogene activation linked to chromosome translocations
Tumor-suppressor loci inactivated by deletion or mutation
Manifestations begin with painless generalized lymphadenopathy
Treatment dependent on disease and patient
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Burkitt Lymphoma (1 of 2)
B-cell non-Hodgkin lymphoma in children
Burkitt lymphoma is a very fast-growing tumor of the jaw and facial bones
Types:
Endemic (linked to EBV)
Sporadic
Immunodeficiency related (AIDS patients)
Treatment is aggressive multidrug regimens
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Burkitt Lymphoma (2 of 2)
Courtesy I. Magrath, MD, Bethesda, Md. From Zitelli BJ et al: Zitelli and Davis’ atlas of pediatric physical diagnosis, ed 6, Philadelphia, 2012, Saunders.
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Lymphoblastic Lymphoma
Relatively rare T-cell non-Hodgkin lymphoma in children
Clone of immature T cells that become malignant in the thymus
Painless lymphadenopathy of the neck, possible chest (mediastinal mass)
Treatment is combined chemotherapy
Plasma Cell Malignancy
Multiple Myeloma (MM)
Malignant proliferation of plasma cells
Infiltrate bone marrow and aggregate into tumor masses in skeletal system
Lytic bone lesions
Manifestations include hypercalcemia, renal failure, anemia, immune abnormalities
Preceded by monoclonal gammopathy of undetermined significance
Several treatment options based on patient and disease
Alterations of Splenic Function
Splenomegaly
Enlargement of spleen
May or may not be pathologic
Congestive splenomegaly
Infiltrative splenomegaly
Hypersplenism
Overactivity of spleen
Causes anemia
Treatment is splenectomy if indicated
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Quantitative Disorders of Platelets
Thrombocytopenia
Decrease in number of circulating platelets
Thrombocythemia
Increase in number of circulating platelets
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Thrombocytopenia (1 of 5)
Defined as platelet count <150,000/mm3
<100,000/mm3: becomes clinically significant
<50,000/mm3: hemorrhage from minor trauma
<15,000/mm3: spontaneous bleeding
<10,000/mm3: severe bleeding
Pseudothrombocytopenia
Error in lab test giving a false reading for thrombocytopenia
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Thrombocytopenia (2 of 5)
Causes:
Decreased platelet production
Viral infections
Drugs or radiation therapy
Chronic renal failure
Bone marrow hypoplasia or cancer
Increased platelet consumption
Heparin-induced thrombocytopenia
Idiopathic (immune) thrombocytopenia purpura
Thrombotic thrombocytopenia purpura
Disseminated intravascular coagulation (DIC)
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Thrombocytopenia (3 of 5)
Heparin-induced thrombocytopenia (HIT)
Adverse drug reaction caused by IgG antibodies targeting heparin-platelet factor 4 complex
Typically causes 50% drop in platelet count
Treatment is withdrawing heparin
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Thrombocytopenia (4 of 5)
Immune (idiopathic) thrombocytopenic purpura (ITP)
Chronic
IgG autoantibody that targets platelet glycoproteins
Antibody-coated platelets are sequestered and removed from the circulation
Acute
Develops after a viral infection is one of the most common childhood bleeding disorders
Manifestations
Petechiae and purpura, progresses to major hemorrhage
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Thrombocytopenia (5 of 5)
Thrombotic thrombocytopenic purpura (TTP)
A thrombotic microangiopathy (small or microvessel disease)
Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries
Familial or acquired
Chronic relapsing TTP
Acute idiopathic TTP
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Thrombocythemia (1 of 2)
Defined as platelet count >400,000/mm3
>1,000,000/ mm3: when symptoms occur
Primary or secondary (reactive)
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Thrombocythemia (2 of 2)
Essential (primary) thrombocythemia (ET)
Myeloproliferative neoplasm involving defect in bone marrow megakaryocyte progenitor cells
Megakaryocytes in the bone marrow are produced in excess
Microvasculature thrombosis or hemorrhage occurs
Secondary thrombocythemia
Following splecetomy because platelets cannot be stored in spleen
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Alterations of Platelet Function
Qualitative alterations demonstrate an increased bleeding time in the presence of a normal platelet count
Manifestations:
Petechiae
Purpura
Bleeding in GI and GU tract, pulmonary mucosa, and gums
Disorders can be congenital or acquired
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Alterations of Coagulation
Caused by problems with clotting factors
Disorders include
Impaired hemostasis
Consumptive thrombohemorrhagic disorders
Disseminated intravascular coagulation
Thromboembolic disorders
Hereditary thrombophilias
Acquired hypercoagulability
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Impaired Hemostasis
Inability of coagulation and stable fibrin clot
Vitamin K deficiency
Vitamin K is necessary for synthesis and regulation of prothrombin, the procoagulant factors (VII, XI, X), and proteins C and S (anticoagulants)
Liver disease
Hepatic cells produce most factors involved in hemostasis
Damage causes production of fewer clotting factors
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Disseminated Intravascular Coagulation (DIC) (1 of 2)
Widespread activation of coagulation and simultaneous hemorrhage
Fibrin clots in small vessels and microvasculature
Blood flow to organs blocked (multiple organ failure)
Consumption of platelets and clotting factors (tendency to bleed despite clots)
Pathway for DIC appears to be excessive and widespread exposure to tissue factor
Sepsis is the most common condition associated with DIC
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Disseminated Intravascular Coagulation (DIC) (2 of 2)
Clinical signs and symptoms demonstrate wide variability:
Bleeding from venipuncture sites or arterial lines
Purpura, petechiae, and hematomas
Symmetric cyanosis of the fingers and toes
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Thromboembolic Disorders
Thrombus: stationary clot attached to vessel wall
Arterial or venous thrombi
Virchow triad
Injury to vessel
Abnormal blood flow
Hypercoagulopathy
Embolus: clot circulating within bloodstream
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Hereditary Thrombophilias
Inherited conditions that increase risk of developing thrombosis
Most autosomal dominant
Mutations affecting
Platelet receptors
Coagulation proteins
Fibrinolytic proteins
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Acquired Hypercoagulability
Deficiencies in proteins S and C and AT-III
Antiphospholipid syndrome
Autoimmune syndrome
Autoantibodies against plasma membrane phospholipids and phospholipid-binding proteins
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Question 3
Thrombocytopenia commonly is seen with which condition?
Multiple myeloma
Hemolytic anemia
Non-Hodgkin lymphomas
Disseminated intravascular coagulation
Note: No input needed to proceed
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Question 3 Answer
Correct Answer: D
Thrombocytopenia is defined as a platelet count below 150,000/mm3 of blood. Most common forms of thrombocytopenia are the result of increased platelet consumption. Examples include heparin-induced thrombocytopenia, idiopathic (immune) thrombocytopenia purpura, thrombotic thrombocytopenia purpura, and disseminated intravascular coagulation. Multiple myeloma is a neoplasm of B cells (immature plasma cells) and mature plasma cells, it is not a disorder that affects platelet counts. Hemolytic anemia results from premature destruction of red cells, not platelets. Non-Hodgkin lymphomas are B-cell neoplasms and usually start out as localized or generalized lymphadenopathy. They do not affect platelet production.
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Case Study (1 of 2)
A 63-year-old woman with diabetes notes that she has a general feeling of tiredness and a loss of appetite. For several months, while on her daily 2-mile walks, she has heard her heartbeat in her ears as a whooshing sound. Very knowledgeable about her disease and compliant with diet and medications, she waits until she sees her endocrinologist for her yearly examination. In the office, she explains her symptoms, and the physician collects a CBC in addition to normal diabetic laboratory tests. The results indicate an anemia, and she is referred to a hematologist. The hematologist reviews her laboratory findings and begins to explain her diagnosis of megaloblastic anemia.
Case Study Discussion Question (1 of 4)
Further testing indicates that the woman suffers from a vitamin B12 deficiency or PA. This condition is often associated with:
Chronic gastritis
Thalassemia
Excessive blood loss
Inadequate dietary intake
Note: No input needed to proceed
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Case Study Discussion Question (2 of 4)
Correct Answer: A
The principal disorder in PA is the absence of IF, which is a transporter required for the absorption of dietary vitamin B12. Environmental factors may cause chronic gastritis, or the condition may be due to the autoimmune diseases of endocrine organs. Microcytic-hypochromic anemia can result from disorders of iron metabolism, heme synthesis, or globin synthesis such as thalassemia. Excessive blood loss and inadequate dietary intake are two different causes of IDA.
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Case Study (2 of 2)
The woman is treated with replacement cobalamin (vitamin B12) over several weeks until the deficiency is corrected. Monthly injections for the remainder of the woman’s life are explained, and she acknowledges the importance of treatment. One year later, the hematologist sees the woman for follow-up laboratory testing. The woman again complains of fatigue. Part of her health screening indicates that she has elevated serum iron and ferritin levels. Confused, the hematologist reviews her medications. She states that she has been taking several iron supplements and a multivitamin with iron daily after reading online that anemia should be treated with iron administration. Discussion with her friends further convinced her that iron was the treatment of choice for anemia. The physician again explains the patient’s initial diagnosis and now informs the woman that she additionally suffers from secondary iron overload.
Case Study Discussion Question (3 of 4)
The treatment for iron overload is:
Vitamin C supplements
Phlebotomy
Aspirin
Plasmapheresis
Note: No input needed to proceed
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Case Study Discussion Question (4 of 4)
Correct Answer: B
The treatment for iron overload is phlebotomy. Approximately 550 ml of whole blood is removed, which is equivalent to 200 to 250 mg of iron. This treatment continues until the ferritin level falls into an acceptable range. Individuals with iron overload should refrain from iron and vitamin C supplements. Aspirin is used for its antithrombotic properties in the treatment of polycythemia vera, the overproduction of red blood cells and platelets and splenomegaly. Plasmapheresis is the process of withdrawing whole blood and removing the liquid portion or plasma from the blood and then replacing it. This process is used in the treatment of multiple disorders including immunologic diseases.
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