blood and lymphoid
Terms
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- Hemopoietic stem cells
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Remain in the bone marrow.
Differentiate into:
-erythroid
-granulocytic-monocytic
-megakaryocytic - Lymphopoietic stem cells
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Migrate to the lymphoid organs
-B-cell lineage
-T-cell lineage - Define ANEMIA.
- A redution in the total circulating erythrocyte mass.
- Morphologic classification of anemias.
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(Less adequate)
-macrocytic
-microcytic
-normocytic - Pathophysiologic classification of anemias.
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-those caused by decreased production of erythrocytes.
-those caused by increased destruction of erythrocytes. - Define APLASTIC ANEMIA.
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A chronic disorder of hemopoietic stem cells that results in cellular depletion of the bone marrow and pancytopenia (decrease in all circulating formed elements).
Most cases IDIOPATHIC (65%), radiation, drugs, benzene, EBV, HIV
Dyskeratosis congenita 20%
Primary lesion involves an inability of stem cells to regenerate and repopulate the marrow.
Bone marrow replaced by fat.
Macrocytic; increased erythrocyte content of fetal hemoglobin. - Paroxysmal Nocturnal Hemoglobinuria (PNH)
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An acquired clonal stem cell disorder that affects all hemopoietic lineages and is characterized by the production of defective erythrocytes and abnormal platelets and granulocytes.
Unusual predisposition of the erythrocytes to complement-mediated lysis.
Deficiency of decay-accelerating factor.
Intermittent periods of hemolysis and hemoglobinuria, often in a nocturnal pattern --> red morning urine.
Consider in Dx of Budd-Chiari syndrome. - Myelodysplastic Syndromes (MDS)
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Encompass a heterogeneous group of disorders that are characterized by clonal proliferation of abnormal stem cells.
Some patients have had occupational exposure to toxic chemicals (benzene).
Ringer sideroblasts, # of myeloblasts determines the classification.
Granulocytes may show DECREASED NUCLEAR LOBATION = PELGER-HUET ANOMALY.
Transforms into acute myelogenous leukemia in 20-40% of patients. - Define Pure Red Cell Aplasia (PRCA)
- An autoimmune disease in which erythroid progenitor and precursor cells are suppressed.
- ACUTE Red Cell Aplasia
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Frequently follows a viral illness, esp. infection with parvovirus B19.
Drug-induced cases, the drug acts as an immunogenic hapten.
Becomes clinically apparent only with underlying disorders characterized by a shortened lifespan of circulating RBC's. - Chronic Constitutional PRCA (Diamond-Blackfan Anemia)
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Caused by INHERITANCE of defective erythroid progenitor cells.
Usually detected during 1st year of life.
Maybe an immunologic component due to dramatic response to corticosteroids. - Chronic Acquired PRCA
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middle-age adults.
Intriguing relationship to thymomas.
Marrow depleted of erythroblasts. - Anemia associated with CHRONIC RENAL FAILURE.
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A normocytic, normochromic anemia occurs in almost all patients with chronic renal disease.
Anemia results from decreased production (inadequate synthesis of erythropoietin by damaged kidneys) and increased destruction.
Bone marrow appears normal.
Circulating erythrocytes have scalloped margins (burr cells). - Anemia Associated with Chronic Disease
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Mild to moderate normochromic or hypochromic anemia is frequent in patients with:
-chronic inflammatory disorders
-chronic infectious diseases
-cancer
Not severe enough to cause major symptoms. Anemia results from decreased iron supply to the developing erythroblast and from a shortened erythrocyte lifespan. - Define Megaloblastic Anemias.
- Characterized by large, nucleated progenitors of RBC's in the bone marrow and are mostly caused by impaired DNA synthesis owing to a defieicny of either vitamin B12 or folic acid.
- Vitamin B12 and Pernicious Anemia
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Defective intestinal absorption of vitamin B12, owing to a lack of production of intrinsic factor, causes pernicious anemia.
Results from an autoimmune attack on the gastric mucosa (parietal cells).
anemia, thrombocytopenia, leukopenia, neurological
spinal cord demyelination, parasthesias, ataxia.
Dx: smear, serum B12, Schilling test
Tx: parenteral Vit B12, neurological symptoms will persist. - Iron Deficiency Anemia
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Most common cause of anemia. Impaired intake of iron owing to iron-poor diet or excessive loss caused by hemorrhage, intravascular hemolysis, pregnancy, or lactation.
RBCs: hypochromic, poikilocytosis, anisocytosis
Loss of iron by blood loss is by far the most common cause of iron deficiency anemia in adults, because each 1 mL of packed erythrocytes contains 1 mg of iron.
Decreased ferritin level; low serum iron level, increased total iron-binding capacity. - Thalassemia
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Thalassemia syndromes are a heterogenous group of heritable anemias that have in common defective synthesis of either the alpha or the beta chains of the normal hemoglobin A tetramer.
All forms characterized by a hypochromic, microcytic anemia owing to reduced or absent synthesis of the complete hemoglobin molecule. - Beta-thalassemia
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>50 distinct mutations have been associated.
Caused by a point mutation on chromosome 11 or by a deletion of part of this gene. - Homozygous B-Thalassemia
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aka Cooley Anemia
Caused by a reduction or absence of Beta chain production.
The excess unpaired alpha chains readily precipitate and destroy both erythroid precursor cells and circulating erythrocytes. Erythrocytes are hypochromic and microcytic.
Facial and cranial bones tend to be enlarged or distorted bc of bone marrow hyperplasia.
Retarded development from birth, severe anemia - increased destruction, ineffective erythropoiesis
Marrow expansion - skeletal deformities
Secondary hemochromatosis
RBCs: hypochromic, microcytic, target cells
Tx: tranfusions, iron chelation - Heterozygous B-Thalaseemia
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aka B-Thalassemia Minor
Increase in hemoglobin A2 (a2delta2). - alpha-Thalassemia
- Reflects the failure of one or more of the 4 alpha-gene loci on chromosome 16 to function.
- The four alpha-thalassemias.
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Silent carrier: deletion of 1 gene.
alpha-thalassemia trait: deletion of 2 genes --> mild hemolytic anemia.
Hemoglobin H disease: 3 genes deleted, moderate hemolytic anemia, beta4.
Deletion of all 4 genes = hydrops fetalis: death in utero or at time of delivery, hemoglobin Barts (gamma4). - Sickle Cell Disease
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Refers to a group of herediatry hemoglobinopathies in which deoxygenated erythrocytes undergo transformation from the normal, biconvave disk to a sickle-shaped structure.
Shape change results from the polymerization of sickle hemoglobin (HbS).
-sickle cell anemia
-sickle cell trait - Sickle cell anemia
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Patients are homozygous for the HbS gene.
Common among blacks = US: 1/650.
The HbS gene is prevalent among areas in which falciparum malaria is endemic (africa), suggesting that heterozygosity confers a selective advantage.
Point mutation in which VALINE is substituted for glutamic acid at the 6th position of the beta-globin chain.
The predominance of hemoglobin S (80-95%) leads to both severe chronic hemolytic anemia and to vasoocclusive disease. - Infarctive crisis and sickle anemia
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sickled erythrocytes obstruct small blood vessels in many organs --> severe pain.
repeated infarcts in spleen --> fibrosis, scarring, splenic atrophy.
skin ulcers at ankles.
infarcts of femoral head - Aplastic Crisis
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Lack of normal splenic function predisposes to bacterial infections, esp. by pneumococci.
Hemolysis continues to the hemoglobin concentration falls = aplastic crisis. -
Effects of sickle cell anemia on:
heart
lungs
brain
kidney
hepatobiliary system
bones
eye -
heart: cardiomegaly and CHF
lungs: pneumonia, infarcts, acute chest syndrome
brain: strokes, cerebral hemorrhage
kidney: renal infarcts and papillary necrosis, decreased concentrating ability.
hepatobiliary system: pigment gallstones
bone: osteomyelitis
eye: retinopathy, blindness - Sickle cell Trait
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the heterozygous form of sickle cell disease (hemoglobin SA).
benign disorder found in 10% of american blacks; africa
asymptomatic unless extremely hypoxic - Hemoglobin C disease
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HbC results from the substitution of LYSINE for glutamic acid in the 6th position of the hemoglobin beta-globin chain.
In homozygous HbC disease, a chronic, mild hemolytic anemia is associated with dehydrated and rigid erythrocytes.
Most prominent feature: presence of numerous target cells. - Glucose-6-Phosphate Dehydrogenase Deficiency
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Refers to a large group of X-linked, hereditary, and hemolytic anemias in which inadequate activity of erythrocyte G6PD predisposes to episodes of hemolysis that are precipitated by drugs or infection.
1/2 male Kurdish Jews afflicted.
Erythrocytes are less resistant to oxidation; hemoglobin is denatured and precipitates as Heinz bodies on the erythocyte membrane.
Expressed only in males.
Patients develop a lethal hemolysis after eating fava beans = FAVISM. - Autoimmune Hemolytic Anemias
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cAused by autoantibodies with specificity for erythrocyte membrane proteins.
Warm-reacting
or
Cold-reacting - Warm-Reacting Autoantibodies
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80%
Women>men
Usually of the IgG class and are often directed at the core antigen of the Rh locus.
Occurs: as an idiopathic disorder (1/2), associated with lymphocytic lymphoma and chronic lymphocytic leukemia, or drug-induced.
Anemia and jaundice. - Erythroblastosis Fetalis
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aka Autoimmune Hemolytic disease of the newborn.
Warm-reacting autoantibodies
Results from immunization of an Rh-negative mother by the erythrocytes of an Rh+ feture. - 2 types of drug-induced hemolytic anemia.
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1) drug changes antigen permanently = antihypertensive drug alpha-methyldopa.
2) drug is temporarily attached to an erythrocyte antigen and antibodies are formed = antiarrhythmic agent quinidine. - Cold-Reacting Autoantibodies
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20%
Usually of IgM type, with specificity for the I antigen that is present on most adult erythrocytes.
Final erythrocyte destruction is HEPATIC (not splenic).
Idiopathic in elderly;
young people with mycoplasmal pneumonia or mono. - Macroangiopathic Hemolysis
- Circulating erythrocytes are vulnerable to shear forces exerted by intravascular protheses in the heart and major arteries (artificial heart valves).
- Microangiopathic Hemolysis
- caused by fragmentation of erythrocytes by fibrin strands in partially obstructed, small peripheral BV's.
- Hypersplenism
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enlarged spleen causes pooling adn sequestration of all cellular elements.
erythrocytes are lysed in the congested splenic cords.
anemia --> erythroid hyperplasia in bone marrow. - define Erythrocytosis
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Usually but not accurately termed POLYCYTHEMIA, encompasses a number of conditions that are characterized by an increased hematocrit.
RBCs: 6-10million/ML - Relative Erythrocytosis
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normal erythrocyte mass with a decreased plasma volume.
common cause: dehydration - Primary absolute erythrocytosis
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aka POLYCYTHEMIA VERA
clonal stem cell disorder in which all progenitor cells continuously proliferate in the absence of growth-stimulating factors.
neoplastic! - Secondary Absolute Erythrocytosis
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Induced by arterial hypoxia under these coniditions:
-high altitude
-pulmonary disease with impaired gas exchange
-cardiac anomalies with a right-to-left shunt (cyanotic heart disease)
-tumors
renal tissue hypoxia --> relase of erythropoietin --> icnreased rate of erythrocyte production. - Course and treatment of aplastic anemia
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Untreated 3-6 mo survival.
Transfusions
Antibiotics
Bone marrrow transplant
Immunosuppression. - Manifestations of aplastic anemia
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Anemia – pallor, fatigue, weakness
Bleeding – mucosa, gingiva, thrombocytopenia
Infections – fevers, gingivitis, pharyngitis, thrush
Ulcers - Pathology of megaloblastic anemias.
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Large erythroid megaloblasts, with loose and immature nuclei, which often have satellite pieces.
Circulating erythrocytes are large, often with an oval shape, are associated with prominent POIKILOCYTOSIS and a TEARDROP configuration.
PMNS- hypersegmented nuclei - Diagnosis for megaloblastic anemia
- serum folate & Vitamin B12
- Epidemiology of thalassemia
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observed among populations tha tinhabited the italian and greek coasts (mediterranean basin)
belt across the middle east, thru parts of pakistan and india, to southeast asia- includes southern regions of former soviet union, china, and northern regions of africa - Diagnosis and treatment of sickle cell anemia
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Diagnosis: prenatal - amniocentesis, c-v biopsy. Postnatal - hemoglobin electrophoresis, DNA
Treatment: transfusions, antibiotics, hydroxyurea (incr. fetal hemoglobin) - oral manifestations of sickle cell anemia
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Mucosal and gingival jaundice, hemorrhage
Irregular bony trabeculae – “stepladderâ€
Mandibular infarct
Osteomyelitis
Aseptic necrosis
Skull – Hair on End - clinical features of erythrocytosis
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headaches, dizziness, visual disturbances, slurring of speech, flushed skin.
Oral - purplish-red mucosa, bruises, gingival bleeding