Week 9 - Haematology Flashcards
Lymphoid Organs consist of Primary and Secondary
Primary: Thymus and bone marrow
Secondary: Spleen, lymph nodes, tonsils, peyers patches
Anaemia
Reduction in the total number of erythrocytes in the circulating blood or in the quality or quantity of hemoglobin due to: Impaired erythrocyte production Acute or chronic blood loss Increased erythrocyte destruction Combination of the above
Symptoms of Anaemia
Fatigue, weakness, dyspnea, and pallor
Physiological manifestation of Anaemia
Reduced oxygen carrying capacity
MACROCYTIC-NORMOCHROMIC ANAEMIA
Macrocytic-large cell
Pernicious Anaemia
Caused by a lack of intrinsic factor required for vitamin B12 absorption
Results in vitamin B12 deficiency
Folate deficiency anaemia
Always caused by lack of folate in the diet
Similar symptoms to pernicious anemia
Mechanism of cause unclear
Folate deficiency also causes neural tube defects in the foetus
MICROCYTIC-HYPOCHROMIC ANAEMIA
Microcytic-small cell
Hypochromic-reduced levels of haemoglobin
Related to:
Disorders of iron metabolism
Disorders of porphyrin and heme synthesis
Disorders of globin synthesis
Iron deficiency anemia
Most common type of anaemia worldwide
Nutritional iron deficiency
Metabolic or functional deficiency
Progression of iron deficiency causes:
Brittle, thin, coarsely ridged, and spoon-shaped nails
A red, sore, and painful tongue
Treatment is by iron replacement therapy (usually ferrous sulfate)
Sideroblastic anemia
Altered mitochondrial metabolism causing ineffective iron uptake and resulting in dysfunctional hemoglobin synthesis
Ringed sideroblasts within the bone marrow are diagnostic
Sideroblasts are erythroblasts that contain iron granules that have not been synthesized into hemoglobin
Erythropoietic hemochromatosis or iron overload is usually present
NORMOCYTIC-NORMOCHROMIC ANAEMIA
Characterized by red cells that are relatively normal in size and hemoglobin content but insufficient in number
Five distinct groups
- Aplastic anaemia
- Posthaemorrhagic anaemia
- Haemolytic anaemia
- Sickle cell anaemia
- Anaemia of chronic inflammation
Aplastic anemia usually means
Pancytopenia (reduction or absence of all 3 blood cell types)
Results from failure or suppression of bone marrow
Treatment is with immunotherapy and bone marrow transplant
Posthaemorrhagic anemia
Acute blood loss from the vascular space
Hemolytic anaemia is caused by
Accelerated destruction of red blood cells
Divided into inherited or acquired conditions
Treated by removing cause of problem, or treating under lying cause
Sickle cell anaemia
Includes sickle cell thalassemia and sickle cell-Hb C disease
Inherited autosomal recessive disorder
Anaemia of chronic inflammation
Mild to moderate anemia seen in:
AIDS, rheumatoid arthritis, lupus, hepatitis, renal failure, and malignancies
Pathologic mechanisms
Decreased erythrocyte life span
Ineffective bone marrow response to erythropoietin
Altered iron metabolism
POLYCTTHAEMIA
Overproduction of red blood cells
Relative polycythemia
Result of dehydration
Fluid loss results in relative increases of red cell counts and Hb and Hct values
Absolute polycythemia
Primary absolute
Abnormality of stem cells in the bone marrow
Secondary absolute polycythemia
Increase in erythropoietin as a normal response to chronic hypoxia or by erythropoietin-secreting tumors
Leukocytosis
Normal protective response to physiologic stressors
Leukopenia
A low white count predisposes a patient to infections
Neutrophil
↑Acute infection; ↓ prolonged infection
Eosinophil
↑Allergy and parasite; ↓surgery, shock, trauma
Basophil
↑Inflammation and allergy; ↓ Hyperthyroidism and steroid therapy
Lymphocyte
↑ acute viral infection; ↓ drug destruction, viral destruction
INFECTIOUS MONONUCLEOSIS
Acute, self-limiting infection of B lymphocytes transmitted by saliva through personal contact
- Commonly caused by the Epstein-Barr virus (EBV)—85%
Symptoms of infectious mononucleosis
Symptoms: fever, sore throat, swollen cervical lymph nodes, increased lymphocyte count, and atypical (activated) lymphocytes
Diagnostic Test for infectious mononucleosis
Monospot qualitative test for heterophilic antibodies
Leukemia
Malignant disorder of the blood and blood-forming organs
Excessive accumulation of leukemic cells
Acute Leukemia
Presence of undifferentiated or immature cells, usually blast cells
Chronic Leukaemia
Predominant cell is mature but does not function normally
4 classifications for leukaemia
Lymphocytic (lymph gland)
Myeloid (bone marrow)
Acute (immature cells)
Chronic (mature, dysfunctional cells)
Signs and symptoms of leukaemias
Anemia Bleeding purpurea, petechiae (red spots) and ecchymosis (bruise) Thrombosis, hemorrhage and DIC Infection Weight loss Bone pain Elevated uric acid Liver, spleen, and lymph node enlargement
MYELOMA
Proliferation of plasma cells
The tumor may be solitary or multifocal (multiple myeloma)
The malignant plasma cells produce abnormally large amounts of one class of immunoglobulin or incomplete immunoglobulin
The unattached light chains of the immunoglobulins (Bence Jones proteins) can pass through the glomerulus and damage the renal tubular cells
Multiple myeloma causes increased osteoclastic bone destruction. Clinical manifestations are:
Cortical and medullary bone loss
Skeletal pain
Recurring infections due to loss of the humoral immune response
LYMPHADENOPATHY
Enlarged lymph nodes that become palpable and tender
Local lymphadenopathy
Drainage of an inflammatory lesion located near the enlarged node
General lymphadenopathy
Occurs in the presence of malignant or nonmalignant disease
Neoplastic disease
Inflammatory conditions
Endocrine disorders
Lipid storage disease
MALIGNANT LYMPHOMAS
Malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues
Two major categories
Hodgkin lymphoma
Non-Hodgkin lymphomas
HODGKINS LYMPHOMA
Characterized by the presence of Reed-Sternberg cells in the lymph nodes
Reed-Sternberg cells are necessary for diagnosis, but not specific to Hodgkin’s
Divided into:
- Classical Hodgkin lymphoma
- Nodular lymphocyte predominant Hodgkin lymphoma
Non-Hodgkin lymphomas are linked to
Chromosome translocations, viral and bacterial infections, environmental agents, immunodeficiencies, and autoimmune disorders
Burkitt Lymphoma
Most common type of non-Hodgkin lymphoma in children
Burkitt lymphoma is a very fast-growing tumor of the jaw and facial bones
Epstein-Barr virus is found in nasopharyngeal secretions of patients
SPLENIC FUNCTION
Largest of the secondary lymphoid organs
Serves as blood reservoir
Supplies lymphocytes for response to blood born microorganisms
Thrombocytopenia
Platelet count <100,000/mm3 Effects of low platelet count are <50,000/mm3—hemorrhage from minor trauma <15,000/mm3—spontaneous bleeding <10,000/mm3—severe bleeding
Causes of Thrombocytopenia
Hypersplenism, autoimmune disease, hypothermia, and viral or bacterial infections that cause disseminated intravascular coagulation (DIC)
Immune thrombocytopenic purpurea (ITP)
Autoimmune disorder where antibodies target platelet glycoprotein
The acute form of ITP that often develops after a viral infection is one of the most common childhood bleeding disorders
Clinical manifestations of Immune thrombocytopenic purpurea (ITP)
Petechiae and purpurea, progressing to major hemorrhage
Thrombotic thrombocytopenic purpurea (TTP)
Unknown cause
A thrombotic microangiopathy
Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries
Chronic relapsing TTP-recurring episodes at approximately 3 week intervals
Acute idiopathic TTP-more common. Fatal if left untreated
Treatments include steroids, plasma exchange or plasmapherisis or splenectomy if treatments unsuccessful
Essential (primary) thrombocythemia
Thrombocythemia is characterized by platelet counts >600,000/mm3
Myeloproliferative disorder of platelet precursor cells
Megakaryocytes in the bone marrow are produced in excess
Microvasculature thrombosis occurs
Alterations to platelet function
Demonstrate an increased bleeding time in the presence of a normal platelet count
Platelet function disorders result from deficiencies in platelet membrane glycoprotein and von Willebrand factor
Manifestations
Petechiae, purpurea, mucosal bleeding, gingival bleeding, spontaneous bruising
Disorders can be congenital or acquired
ALTERATIONS OF COAGULATION
Vitamin K deficiency
Vitamin K is necessary for synthesis and regulation of prothrombin, the prothrombin factors (II, VII, XI, X), and proteins C and S (anticoagulants)
Liver disease
Liver disease causes a broad range of homeostasis disorders
Defects in coagulation, fibrinolysis, and platelet number and function
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
Complex, acquired disorder in which clotting and hemorrhage occur simultaneously
DIC is the result of increased protease activity in the blood caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis
Endothelial damage is the primary initiator of DIC in the presence of sepsis
Clinical signs and treatment of (DIC)
Bleeding from venipuncture sites
Bleeding from arterial lines
Purpurea, petechiae, and haematomas
Symmetric cyanosis of the fingers and toes
Treatment is to
Remove the stimulus
Restore haemostasis
Maintain organ viability
Iron deficiency anaemia in children
Most common blood disorder of infancy and childhood
Lack of iron intake or blood loss
Manifestations
Irritability, decreased activity tolerance, weakness, and lack of interest in play
Acquired congenital hemolytic anemia
Hemolytic disease of the newborn (HDN)
Alloimmune disease
Maternal antibody directed against fetal antigens
ABO incompatibility occurs in 20% to 25% of cases
Rh incompatibility occurs in less than 10%
Also termed erythroblastosis fetalis
Hemolytic disease of the newborn (HDN)
Manifestations: Anemia Hyperbilirubinemia Icterus neonatorum (neonatal jaundice) Kernicterus (bilirubin deposition in the brain)
Anemia of infectious disease
Diseases initially acquired by the mother and transmitted to the fetus
Results in hemolytic anemia
Likely due to injury to the erythrocyte membranes or erythrocyte precursors by infectious organism
Glucose-6-phosphate dehydrogenase deficiency (G6PD)
Inherited, X-linked, recessive disorder
G6PD is an enzyme that helps erythrocytes maintain metabolic processes despite injurious conditions
Certain drugs, foods, infection fever, acidosis, hypoxaemia act as stressors
Asymptomatic unless stressors are present
Hereditary spherocytosis
Autosomal dominant trait
Abnormality of proteins or spectrins of the erythrocyte membrane leading to an increased concentration of intracellular sodium
Causes splenomegaly and microcytic spherocytes
Haemolytic anaemias result
Sickle cell disease in children
Disorders characterized by presence of an abnormal hemoglobin (Hgb S)
Deoxygenation and dehydration cause the red cells to solidify and stretch into an elongated sickle shape
Sickle cell disease can result in:
Vaso-occlusive crisis (thrombotic crisis), aplastic crisis, sequestration crisis, and hyperhemolytic crisis
Sickle cell trait
Child inherits Hgb S from one parent and Hgb A from another
Thalassemias
Autosomal recessive disorders
Synthesis of the globin chains of the hemoglobin molecule is slowed or defective
Major—homozygous inheritance
Minor—heterozygous inheritance
Hemophilias
Serious bleeding disorders
Hemophilia A (classic hemophilia-factor VIII deficiency) Hemophilia B (Christmas disease-factor IX deficiency) Hemophilia C (factor XI deficiency) von Willebrand disease (factor VIII deficiency)
Congenital hypercoagulability and thrombosis
Thrombophilia (increase of platelets) Protein C deficiency Neonatal purpurea fulminans (usually fatal syndrome) Protein S deficiency Antithrombin III (AT III) deficiency
ANTIBODY-MEDIATED HAEMORRHAGIC DISEASE
Idiopathic thrombocytopenic purpurea
Autoimmune or primary thrombocytopenic purpurea
Autoimmune neonatal thrombocytopenia
Infants delivered to mothers with ITP
Autoimmune neonatal thrombocytopenia purpurea
Autoimmune vascular purpurea
LEUKAEMIA in children
Most common malignancy of childhood
80% to 85% are acute lymphoblastic leukemias
LYMPHOMA in children
Non-Hodgkin lymphoma Nodular and diffuse Hodgkin lymphoma Rare in childhood Infectious mode of transmission Many children with Hodgkin lymphoma demonstrate a high antibody titer to Epstein-Barr virus (EBV)
