pathology ot the blood and the lymphoid organsustavpatologie.upol.cz/_data/section-1/225.pdf ·...
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Pathology ot the blood and the lymphoid organs
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Anemia
• Total reduction of the circulating erythrocyte mass (decreased hemoglobin, hematocrit, erythrocytes)
• Symptoms: redistribution of blood to vital organs, tachycardia, shortness of breath. Angina, weakness, atrophic glossitis, angular stomatitis, koilonychia (spoon shaped fingernails)
• Classification – Morphological: macrocytic, microcytic, normocytic
– Pathophysiology:
1) decreased production
2) increased destruction
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ad 1) decreased production
stem cell disorders aplastic anemia paroxysmal nocturnal hemoglobinuria myelodysplasias progenitor cell disorders chronic renal failure chronic diseases precursor cell disorders megaloblastic anemia iron deficiency talassemia
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Aplastic anemia
• Pancytopenia (varying severity -20% survive a year)
• Fanconi anemia – AR, manifested in the first decade and associated with variety of congenital anomalies (renal, skeletal, cutaneous)
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Paroxysmal nocturnal hemoglobinuria
• Production of defective erythrocytes (also platelets and granulocytes)
• Intermittent periods of hemolysis + often thrombotic complications
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Anemia with chronic renal failure
• Normocytic, normochromic
• Proportional to the degree of uremia
• Decreased production – inadequate synthesis of erythropoietin + role of uremic toxins suppressing precursors
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Anemia with chronic diseases
• Normochromic or hypochromic
• Chronic inflammatory disorders (rheumatoid arthritis, lupus erythematosus)
• Chronic infectious diseases (TBC, AIDS)
• Cancer
• Decreased iron supply+shortened erythrocyte life span+ impaired BM response to erythropoietion
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Megaloblastic anemia
Impaired DNA synthesis – megaloblatic transformation Neurologic defects (ataxia, weak muscle, difficulty walking)) Smooth and tender tongue
1) Vitamin B12 (meat, fisch, liver, milk) and pernicious anemia Autoimmune gastritis Gasterectomy Pathology of terminal ileum (onflamation, cancer, operation, parasites) 2) Folic acid deficiency (leafy vegetables, eggs Inadequte dietary intake – alcoholics, poor nutrition, celiac disease, tropic sprue, some medications
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Iron deficiency anemia
• Adequate diet -20 mg of iron daily, of which1-2 mg is absorbed (duodenum)
• The most common cause of anemia
– Impaired intake (iron – poor diet)
– Excessive loss (hemorrhage ((menstruation, GIT or urinary blood loss)), pregnancy, lactation
• Hypochromic, microcytic
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Talassemia
• Defective synthesis of the alpha or beta chains of the hemoglobin
• Hypochromic, microcytic anemia
• Mediterranean countries, Middle East, Pakistan, India, China, frequent in countries where malaria is endemic (heterozygotes have milder symptoms of malaria)
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Beta talassemia
• (more then 50mutations)
• Heterozygous (moderate reduction of normal hemoglobin, mild anemia)
• Homozygous – Absence of beta hemoglobin,
nearly fetal hemoglobin, erytrocytes – anisocytosis, poikilocytosis, target cell configuration,
– Enlargement of facial and cranial bones -BM hyperplasia
– Extramedullary hematopoesis
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ad 2) increased destruction of erythrocytes
• Intrinsic
– Hemoglobinopathies
– Membrane defects
– Enzyme disorders
• Extrinsic
– Antibody mediated destruction
– Mechanical destruction
– Hypersplenism
– Acute blood loss
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Hemoglobinopathies
Sickle cell diseases • Deoxygenated erythocytes –
transformation from normal biconcave to sickle shaped – HbS hemoglobin
• Infarctive crisis • Aplastic crisis (lack of spleen
function – bacterial infections • Cardiac, kidney failure,
osteomyelitis, pneumonias, strokes, pigmented gallstones, bone necrosis, retinopathy, blindness
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Membrane defects
a) Hereditary spherocytosis = inherited hemolytic anemia – defects in the cytoskeleton, normocytic hyperchromic anemia+ splenomegaly (curative splenectomy)
b) Hereditary ellipsocytosis
c) Acanthocytosis
glucocse-6-phosphate dehydrogenase deficiency
(hemolytic anemia agravated by infections and drugs)
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Autoimmune hemolytic anemias
• Warm reacting antibodies (80%)
– CLL, lymphoma, colagen vascular diseases, cancers, drugs
– Erythroblastosis fetalis (hemolytic disease of the newborn, immunization of Rh-negative mothers)
• Cold reacting antibodies
– Infectious mononucleosis, CLL
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Mechanical destruction
• Macroangiopathic
– Intravascular prosthesis in the heart and large arteries
• Microangiopathic
– Fragmentation by fibrin strands (DIC, TTP)
• March hemoglobinuria
– External pressure- trauma in long distance walk
• Hypersplenism
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Erythrocytosis
• Relative – Normal numbers in decreased volume - dehydratation
• Absolute – Arterial hypoxia High altitude Pulmonary disease Cardiac anomalies with a right to left shunt Hemoglobinopathiee – Oversecretion of erythropoietin in absence of hypoxia renal cysts, hydropenhrosis, carcinoma, cereberal hemagioblastoma, uterine leiomyoma
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Quantitative disorders of neutrophils
Neutropenia
• Decreased production
– Irradition
– Drug induced
– Viral inf.
– congenital
• Ineffective production
– Megaloblastic anemia
– Myelodysplastic sy
• Increased destruction
– Autoimmune (drugd, viruses, inflammations)
• Increased margination
Leukocytosis
• Infections (bacterial)
• Immunologic – inflammatory
– Rheumatois arthritis, vasculitis, rheumatic fever
• Tissue becrosis
• Neoplasia
• Hemorrhage
• Hemolysis
• Metabolic disorders
– Acidosis, uremia, gout
• Endocrinologic disorders
– Hyperthyroidism, glucocorticoids
• Pregnancy
• Toxins
• Physical stimuli
– Cold, heat
• Emotional stress
• Hereditary neutrophilia
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• Leukemoid reaction
In acute infection – neuthrophilia may be so pronouced – may be mistaken for leukemia
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Eosinophilia
• Allergic disorders
• Skin diseases
• Parasitic infections
• Malignant neoplasm – Lymphoma, leukemia, myeloproliferative sy, epithelial
malignancy
• Collagen vascular disease – Dermatomyositis, polyarteriitis nodosa
• Idiopatic
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Basophilia
• Allergy • Inflammation
– Juvenile rheumatoid arthritis – Ulcerative colitis
• Infection – Viral – TBC
• Neoplasia – Myeloproliferation – Mastocytosis – Basophilic leukemia – Hodgkin´s disease
• Endocrinopathy myxedema estrogen administration
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Trombocytopenia
Decreased production – Aplastic anemia – Bone marrow suppression (CML)
• Ineffective production – Megaloblastic anemia – Myelodysplasias
• Increased destruction – Idiopathic thrombocytopenic purpura
(immune mediated) – CLL, HIV – Drug induced (heparin, sulpfonamides,
digoxin, penicillin – Consumptive (DIC, TTP) – Post transfusion
• Increased sequestration • Dilutional
Symptoms Bleeding episodes – epistaxis. Menorrhagia, ecchymoses, retinal, mucosal – gingival, intestinal b., CNS b. life threatening hemorrhages - rare
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Thrombocytosis
• Reactive
– Iron deficiency anemia
– Splenomegaly
– Cancer
– Idiopathic
– cancer
• Clonal
– Myeloproliferative diseases
• Episodes of thrombosis and bleeding
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Lymph node pathology
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Lymph node pathology
• Acute lymhangitis – Suppurative
• Reactive hyperplasia – Follicular:
• Nonspecific inflammation • Rheumatoid arthritis • Syphilis • AIDS lymhadenopathy
– Paracortical (interfollicular) • Viral (infectious mononicleosis,
varicella-herpes inf, measles CMA inf
– Sinusoidal • Sinus histiocytosis (tumors, infections)
– Mixed • Toxoplasmosis
– Necrotizing – Granulomatous
• Cat-scratch disease • Lymphogranuloma inguinale • mesenterial lymphadenitis • Specific inflammations • Crohn diseases
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Pathology of the spleen • Hypersplenism – functional disorder –
anemia, leukopenia, thromocytopenia+compensatory BM hyperplasia
• Hyposplenism – risk of severe bacteriemia, leukocytosis, thrombocytosis
• Accessory spleen
• Secondary tumors – only late in the course
Splenomegaly
• Mild (up to 500 g)
– Acute infections bacterial
– Infectious mononuclerosis
– Acute venostasis
– Autoimmune diseases
• Moderate (500-1000g)
– Chronic venostasis
– Acute leukemia
– Hereditary spherocytosis
– Autoimmune hemolytic anemia
– Amyloidosis (AA)
– Niemann-Pick storage disease
• Severe (over 1000g)
– Chronic myeloid leukemia
– CLL
– Hairy cell leukemia
– Gaucher storage disease
– Primary tumor
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Oral manifestation of hematological diseases
• Haemorrhage
• Ulcerations, necrosis
• Tumorous infiltration
• Infections
• Lymphadenopathy
• Autoimmune diseases
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Haemorrhage
myeloproliferative diseases
• caused by trombocytopenia,
• mucosal petechiae
• bleeding from gums in teeth brushing
• prolonged bleeding after tooth extraction
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Ulceration, necrosis
• patients with granulocytopenia
• Locations: gingiva, tongue, palate, bucal mucosa.
• Very painful
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Ulceration, necrosis
• Infections (associated with the basic disease or with therapy)
▫ Bacterial
▫ Viral
▫ Mycotic (Candida, Aspergillus, Mucormycosis)
• Most infections in granulocytopenia are caused by E. colli, Klebsiella and Pseudomonas.
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Herpes zoster • Elderly people
• Immunosupression, often in Hodgkin and T lymphomas, leukaemias
• Lesion follow peripheral nerves–n. Trigeminus+ n facialis (paresis)
• Strong burning pain
• Postherpetic neuralgy
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Infiltration
• In leukaemic patients – diffuse gingival hypertrophy – teeth are covered by gingiva (often bleeding and infected)
• connective tissue is infiltrated by leukaemic cells
• Tissue may be necrotic due to thromboses – teeth may come loose (periostal necroses)
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Lymhadeopathy
• SUBMANDIBULAR AND CERVICAL LYMPH NODES
CLL
Hodgkin‘s lymphoma
Burkitt lymphoma
• ALL – tonsilar hypertrophy
– obstruction of air - Waldayerova lymphatic tissue
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AL amyloidosis
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Others
• Mikulicz syndrome (xerostomy a xerophtalmy) in leukaemic infiltrations of salivary glands
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Others
Paraneoplastic pemphigus
• Rapid course, fatal
• Changed cellular antigenicity (tumour neoantigens or structural changes of normal cells)
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Others
• Apthous stomatitis