anemias Flashcards
what are anemias?
reduction of the total circulating red blood cell mass below normal limits => tissue hypoxia
what changes would you see in cell morphology as a result of anemia?
RBC size
degree of hemoglobinization (reflected in color of RBCs)
shape
what is the difference between microcytic hypochromic anemia and macrocytic anemia?
micro = disorders of Hb synthesis (usually iron deficiency)
macro = due to abnormalities that impair maturation of erythroid precursors in bone marrow
what are the cell indicies of anemia?
1: mean cell volume
2: mean cell Hb
3: mean cell Hb concentration
4: RBC distribution width
what are the features of hemolytic anemias?
1: premature destruction of red cells and a shortened red cell life span below the normal 120 days
2: elevated erythropoietin levels and a compensatory increase in erythropoiesis
3: accumulation of hemoglobin degradation products released by red cell breakdown derived from Hb
what is extravascular hemolysis? what is it caused by? what are the clinical features?
premature destruction of RBCs within phagocytes
due to alterations that render RBC less deformable
clinical features = anemia, splenomegaly, jaundice
what causes intravascular hemolysis? what are the consequences?
mechanical injury, complement fixation, intracellular parasites, exogenous toxic factors
manifested by: anemia hemoglobinemia hemoglobinuria hemosiderinuria jaundice
what are the morphological changes of anemia?
increased production of erythropoietin => erythroid differentiation => increased numbers of erythroid precursors in marrow
compensatory increases in erythropoiesis => reticulocytosis in peripheral blood
what is hereditary spherocytosis (HS)?
inherited disorder caused by intrinsic defects in RBC membrane skeleton that render RBCs spheroid, less deformable, and vulnerable to splenic sequestration and destruction
usually autosomal dominant - otherwise due to inheritance of two different defects
results in decreased lifespan of RBCs to 10-20 days - reduced stability of the lipid bilayer => loss of membrane fragments as red cells age in the circulation
what does spherocytosis look like?
on smears - abnormally small, dark-staining red cells lacking the central zone of pallor
what does HS morphologically look like?
spherocytosis reticulocytosis marrow erythroid hyperplasia hemosiderosis mild jaundice cholelithiasis (pigment stones)
what are aplastic crises? what triggers them?
crisis in patients with chronic hemolytic anemia of mild to moderate severity
usually triggered by parvovirus infection - kills RBC progenitors
what are hemolytic crises?
in patients with anemia
produced by intercurrent events leading to increased splenic destruction of red cells
what is the consequence of glucose-6-phosphate dehydrogenase deficiency?
abnormalities in hexose monophosphate shunt or glutathione metabolism resulting from deficient or impaired enzyme function reduce ability of RBCs to protect themselves against oxidative injuries and lead to hemolysis
normally, G6PD reduces NADP to NADPH while oxidizing glucose-6-phos
NAPDH provides reducing equivalents needed for conversion of oxidized glutathione to reduced glutathione - protects against oxidant injury
mutation causes misfolding of the protein - more susceptible to proteolytic degradation
get episodic hemolysis when there are exposures that generate oxidant stress - usually infections - free radicals produced by leukocytes
what are heinz bodies? what happens to them (ie how are they removed) and what are the consequences for the cells?
when G6PD-deficient RBCs exposed to oxidants - reactive sulfhydryl groups cross-link on globin chains - become denatured and make membrane-bound precipitates
seen as dark inclusions within RBCs stained with crystal violet
macrophages in spleen “pluck out” the heinz bodies, but if the cells have membrane damage, can retain abnormal shape - cells will appear to have a bite taken out of them
what are the characteristics of acute intravascular hemolysis? when does it occur?
characterized by anemia, hemoglobinemia, hemogloinuria
in patients with G6PD deficiency, occurs 2-3 days after exposure to oxidants
what is autospenectomy? in what patients does it occur?
in patients with sickle cell anemia
spleen enlarged in childhood by red pulp congestion due to trapping of sickle cells but over time chronic erythrostasis => splenic infarction, fibrosis, and progressive shrinkage => only small nubbin of fibrous tissue by adolescence or early adulthood
what are vaso-occlusive crises? what can trigger it? where does it usually occur?
occur in sickle cell anemia patients
episodes of hypoxic injury and infarction that cause severe pain
triggered by infection, dehydration, acidosis or unknown
occurs most commonly in bones, lungs, liver, brain, spleen, penis
what is acute chest syndrome?
particularly dangerous type of vaso-occlusive crisis involving lungs
typically presents as fever, cough, chest pain, pulmonary infiltrates
pulmonary inflammation => sluggish blood flow => sickilng and vaso-occlusion
what are sequestration crises?
occur in children with intact spleens (but sickle cell anemia)
massive entrapment of sickle RBCs => splenic enlargement, hypovolemia, sometimes shock
what are aplastic crises? what causes them?
in patients with sickle cell anemia
due to infection of RBC progenitor cells by parvovirus B19
what are thalassemia syndrome?
heterogeneous group of disorders caused by inherited mutations that decrease the synthesis of adult hemoglobin (HbA)
due to deficient synthesis of either the alpha or beta chain
what will beta-thalassemia look like histologically?
blood smears have abnormalities in RBC size and shape, microcytosis and hypochromia
target cells with Hb in center of cell, basophilic stippling, fragmented RBCs
expansion of hematopoietically active marrow esp apparent in bones of face and skull
enlarged spleen due to phagocyte hyperplasia and extramedullary hematopoiesis
liver and lymph nodes can also be enlarged
hemosiderosis and secondary hemochromatosis due to iron overload
what anemic disease can cause hydrops fetalis?
the most severe form of alpha-thalassemia
deletion of all four alpha-globin genes
as a result, the fetal gamma chains make tetramers, but the affinity for O2 is so high that almost none gets to tissues
what is paroxysmal nocturnal hemoglobinuria (PNH)? what causes it?
due to acquired mutations in PIGA gene - encodes for an enzyme that’s essential for synthesis of certain cell surface proteins
results in deficient GPI-linked proteins
x-linked
results in blood cells that are deficient in components of the complement pathway
thrombosis is leading cause of death in these patients
what are immunohemolytic anemias?
due to antibodies that bind to RBCs => premature destruction
what is warm antibody type?
most common form of immunohemolytic anemia
50% of cases idiopathic, rest due to predisposing condition or drug
most causative antibodies = IgG, but can be IgA
what is cold agglutinin type?
form of immunohemolytic anemia due to IgM antibodies binding RBCs avidly at low temps
can appear transiently following infections
IgM only binds in vascular beds where them temp falls - agglutinates RBCs and fixes compliment => deposition of C3b in spleen, liver, and bone marrow
what is cold hemolysin type?
type of immunohemolytic anemia
cold hemolysins = autoantiboides responsible for paroxysmal cold hemoglobinuria => intravascular hemolysis and hemoglobinuria
IgGs bind to P blood group antigen on RBC surface in cooler vascular beds
cells move to warmer regions => complement-mediated lysis (compliment cascade functions better at warmer temps)
most often seen in children after viral infections
what is the cause of megaloblastic anemias?
impairment of DNA synthesis => morphologic changes including abnormally large erythroid precursors and red cells
includes pernicious anemia and folate deficiency anemia
what is the morphology of megaloblastic anemias?
RBCs that are macrocytic and oval
larger than normal, have ample Hb, lack central pallor of normal RBCs - can be hyperchromic
variation in size and shape
reticulocyte count low
if severe, may be nucleated RBC progenitors in circulation
neutrophils larger than normal and hypersegemented (5+ nuclear lobules instead of normal 3-4)
giant metamyelocytes and band forms of granulocytic precursors
what is pernicious anemia? what causes it?
specific form of megaloblastic anemia due to autoimmune gastritis and attendent failure of intrinsic factor production => vitamin B12 deficiency
what would you see histologically with pernicious anemia?
chronic atrophic gastritis - loss of parietal cells, prominent infiltrate of lymphocytes and plasma cells, megaloblastic changes in mucosal cells
autoantibodies often present
atrophy of fundic glands - affecting both chief cells and parietal cells
CNS lesions
what is the morphology of anemia due to iron deficiency?
mild to moderate increase in erythroid precursors
disappearance of stainable iron from macrophages in bone marrow (using prussian blue stains)
small and pale RBCs - zone of pallor enlarged
what is aplastic anemia?
syndrome of chronic primary hematopoietic failure and attendent pancytopenia
if immune derived, activated T cells suppress hematopoietic stem cells
could also be due to fundamental stem cell abnormality
what is the morphology of aplastic anemia?
hypocellular bone marrow devoid of hematopoietic cells
lots of fat cells, fibrous stroma, and scattered lymphocytes and plasma cells
what is pure red cell aplasia?
primary marrow disorder in which only erythroid progenitors are supressed
what is myelophthisic anemia?
form of marrow failure in which space-occupying lesions replace normal marrow elements - usually due to metastatic cancer
