QUANTITATIVE RED CELL DISORDERS Flashcards
QUANTITATIVE RED CELL DISORDERS
- IRON DEFICIENCY ANEMIA
- ANEMIA OF CHRONIC INFLAMMATION
3.SIDEROBLASTIC ANEMIA
Lead Poisoning
Porphyrias
4.IRON OVERLOAD
5.MEGALOBLASTIC ANEMIA
-develops due to inadequate intake, increased need, impaired absorption, and chronic blood loss
- develops slowly, progressing through stages that physiologically blend into one another.
IRON DEFICIENCY ANEMIA
Storage compartment
ferritin
Transport compartment
transferrin
Functional compartment
hemoglobin, myoglobin, cytochrome
Hemoglobin N
Serum Iron N
TIBC INCREASED
Ferritin DECREASED
STAGE 1 IRON DEFICIENCY ANEMIA IDA
Hemoglobin N
Serum Iron DECREASED
TIBC INCREASED
Ferritin DECREASED
Stage 2 IDA (Transport iron depletion)
Hemoglobin DECREASED
Serum Iron DECREASED
TIBC INCREASED
Ferritin DECREASED
Stage 3 IDA
( Functional iron depletion)
IRON DEFICIENCY ANEMIA SYMPTOMS
-Fatigue, weakness, shortness of breath (especially with exertion)
-Pallor is evident in light-skinned individuals
-Pallor in the conjunctiva, mucous membranes or palmar creases of dark-skinned individuals
-Glossitis
-Angular cheilosis
-Koilonychia
-Pica
Laboratory diagnosis:
Screening: IDA should be suspected when the CBC findings show a ?
hypochromic, microcytic anemia with an elevated
RDW but no consistent shape changes to the RBC
Serum ferritin DECREASED
Serum iron DECREASED OR NORMAL
TIBC INCREASED
Transferrin saturation DECREASED
Iron deficiency anemia or IDA
-inflammation is the unifying factor
- sideropenia in the face of an ABUNDANT IRON stores is the central feature
- the impaired ferrokinetics is the more significant cause of the anemia
ANEMIA OF CHRONIC INFLAMMATION
Substances that contribute/explain the inconsistency of decreased serum iron despite the abundant iron stores:
1.Hepcidin - a hormone produced by hepatocytes to regulate body iron levels
2.Lactoferrin - an iron-binding protein in granules of neutrophils
3.Ferritin
Peripheral blood picture is that of mild anemia, with hemoglobin concentration usually 8-10 g/dL, and without reticulocytosis
ANEMIA OF CHRONIC INFLAMMATION
Normocytic, normochromic.
Prussian blue stain of the bone marrow confirms abundant stores of iron in macrophages.
ANEMIA OF CHRONIC INFLAMMATION
are a diverse group of diseases that include hereditary and acquired conditions
SIDEROBLASTIC ANEMIA
- the metal affects the central nervous system and the hematologic system
- interferes with porphyrin synthesis
Lead Poisoning
- basophilic stippling is a classic finding
- represents punctate basophilia
Lead Poisoning
-are diseases characterized by impaired production of the porphyrin component of heme
- is the most often used to refer to the hereditary conditions that impair production of protoporphyrin
Porphyrias
most common inherited porphyria
Acute intermittent hepatic porphyria
Deficient enzyme:
Uroporphyrinogen I synthetase/ Porphobilinogen synthase
Acute intermittent hepatic porphyria
Increased delta-aminolevulinic acid and porphobillinogen in urine
Acute intermittent hepatic porphyria
Deficient enzyme
Coproporphyrinogen II oxidase
Hereditary coproporphyria
Increased coproporphyrin III in urine and feces
Hereditary coproporphyria
Deficient enzyme
Protoporphyrinogen oxidase/ Porphobilinogen oxidase
Variegate porphyria
Increased porphobilinogen and delta-aminolevulinic acid in urine and protoporphyrinogen and coproporphyrin in feces
Variegate porphyria
Deficient enzyme
Uroporphyrinogen decarboxylase
Cutaneous hepatic porphyria
Increased uroporphyrin I in urine
Cutaneous hepatic porphyria
Deficient enzyme
Uroporphyrinogen III cosynthase
Congenital erythropoietic porphyria
Increased uroporphyrinogen I and coproporphyrinogen I in urine, feces, and bone marrow
Congenital erythropoietic porphyria
Congenital erythropoietic porphyria involved?
Erythroid
Deficient enzyme
Delta-aminolevulinic acid dehydrase and ferrochelatase
Acquired porphyria
Porphyrias diseases
1.Acute intermittent hepatic porphyria
2.Hereditary coproporphyria
3.Variegate porphyria
4.Cutaneous hepatic porphyria
5.Congenital erythropoietic porphyria
6.Acquired porphyria
1.Acute intermittent hepatic porphyria
2.Hereditary coproporphyria
3.Variegate porphyria
4.Cutaneous hepatic porphyria
Involved?
HEPATIC/LIVER
excess accumulation of iron results from acquired or hereditary conditions in which the body’s rate of iron acquisition exceeds the rate of loss
IRON OVERLOAD
excess iron are stored in the form of ferritin and hemosiderin (non-metabolically active form of ferritin) within cells.
IRON OVERLOAD
IRON OVERLOAD
accumulation of iron in the macrophages, with less parenchymal injury
ACQUIRED Transfusion-related hemosiderosis
IRON OVERLOAD
-mutations of HFE gene remain the most common
- individuals usually harbor 20 to 30 g of iron by the time their disease usually becomes clinically evident
- accumulation of iron in the parenchymal cells, with tissue injury
- traditional characterization: Bronzed diabetes
Hereditary hemochromatosis
Elevated transferrin saturation or serum ferritin Abnormal results on common tests of liver function
IRON OVERLOAD
- defective nuclear maturation due to impaired DNA synthesis due to Vitamin B12 or folate deficiency
- the resulting DNA is nonfunctional, DNA replication process is incomplete, and cell division is halted
- ineffective erythropoiesis
MEGALOBLASTIC ANEMIA
- defective nuclear maturation due to impaired DNA synthesis due to Vitamin B12 or folate deficiency
- the resulting DNA is nonfunctional, DNA replication process is incomplete, and cell division is halted - ineffective erythropoiesis
MEGALOBLASTIC ANEMIA
Causes of Folate deficiency:
- Inadequate intake
- Increased need
- impaired absorption
- impaired use of folate
- excessive loss of folate
Causes of Vitamin B12 deficiency
- Inadequate intake
- increased need
- impaired absorption
1. Failure to separate vitamin B12 from food proteins
2. Failure to separate vitamin B12 from haptocorin
3. Lack of intrinsic factor
4. Malabsorption
5. Competition for vitamin B12
- is an autoimmune disorder characterized by impaired absorption of vitamin B12 due to a lack of intrinsic factor
Pernicious Anemia
- production of antibodies to intrinsic factor and gastric parietal cells
- autoantibodies are directed against the a- and b- subunit of the gastric H+/K+ -ATPase, a hydrogen transporting enzyme, responsible for the acidification of the stomach lumen
Pernicious Anemia
- caused by mutations in the genes for either cubilin or amnionless
Imerslund-Gräsbeck syndrome
Systemic manifestations of folate and vitamin B12 deficiency:
- general symptoms related to anemia
- glossitis
- gastritis, nausea, constipation
- neurologic symptoms may be pronounced and may even occur in the absence of anemia (Vitamin B12 deficiency)
Systemic manifestations of folate and vitamin B12 deficiency:
- general symptoms related to anemia
- glossitis
- gastritis, nausea, constipation
- neurologic symptoms may be pronounced and may even occur in the absence of anemia (Vitamin B12 deficiency)
Laboratory diagnosis:
SCREENING TESTS MEGALOBLASTIC ANEMIA
CBC
PBS
BILIRUBIN
LACTATE DEHYDROGENASE
decreased hemoglobin and hematocrit levels, pancytopenia, reticulocytopenia
CBC
oval macrocytes, hypersegmented neutrophils with six or more lobes, nucleated RBCs, Howell-Jolly bodies, basophilic stippling, Cabot rings
PBS
increased
Bilirubin
Lactate dehydrogenase
- are macrocytic anemias in which DNA is unimpaired
- lack hypersegmented neutrophils and oval macrocytes in the peripheral blood and megaloblasts in the bone marrow
Macrocytic nonmegaloblastic anemias
Remains the reference confirmatory test to identify megaloblastic appearance of the developing RBCs
Bone marrow examination
Competitive binding chemiluminesence
Serum Vitamin B12
GC-MS
Methylmalonic acid
Used to diagnose pernicious anemia
Schillings test
Pathophysiology includes:
- destruction of hematopoietic stem cells due to injury by drugs, chemicals, radiation, viruses, or autoimmune mechanisms
- premature senescence and apoptosis
- ineffective hematopoiesis due to stem cell mutations or vitamin B12 or folate deficiency
- disruption of the bone marrow microenvironment that supports hematopoiesis - decreased production of hematopoietic growth factors or related hormones
- loss of normal hematopoietic tissue
BONE MARROW FAILURE
include pancytopenia, reticulocytopenia, bone marrow hypercellularity, and depletion of hematopoietic stem cells
APLASTIC ANEMIA
Acquired Aplastic Anemia
Two major categories:
- Idiopathic acquired aplastic anemia - 70%
- Secondary acquired aplastic anemia - 10%-15%
