Pathology of red cell disorders - Zaloga Flashcards
1
Q
anemia
A
- reduction of total circulating red cell mass causing reduced O2 carrying capacity of blood –> hypoxia
- diagnosed through hematocrit or Hb [] of blood
- effects: fatigue, SOB, affects the heart, liver, and CNS
2
Q
red cell indices
A
- MCV = average volume of a RBC in sample
- MCH = average content of Hb in a red cell sample
- MCHC = average [] of Hb in a red cell sample
- RDW = variation of RBCs in a sample
3
Q
reticulocytes
A
- immature RBCs released from the bone marrow
- high count –> marrow is being stimulated
4
Q
microcytic anemias
A
- Fe deficiency
- anemia of chronic disease
- sideroblastic
- thalassemias
5
Q
macrocytic anemias
A
- vit. B12 or folate deficiency
- liver disease
- chemotherapy
6
Q
Heinz bodies
A
- unstable Hb in the cytoplasm
- can lead to thalassemias and HbH disease
7
Q
megaloblastic anemias
A
- type of macrocytic anemia
- impairment of DNA synthesis –> ineffective hematopoiesis –> cells don’t divide & appear larger –> pancytopenia
- Vit. B12 and folate deficiency –> cannot make thymidine
- premature apoptosis in the marrow –> phagocytosed by Macs
- large red cells due to RNA synthesis (can still make uridine)
- immature nucleus but mature cytoplasm**
- macrocytic RBCs, hypersegmented neutrophils**
8
Q
normal B12 metabolism
A
- requires intrinsic factor (made by parietal cells) for duodenum absorption
- B12 binds to salivary haptocorrin –> pancreatic proteases release B12 in duodenum to bind to IF –> cubulin receptor in ileum for IF/B12 –> transform into transcobalamin II to travel in plasma to liver etc.
9
Q
megaloblastic anemia - B12 deficiency
A
- no reduced form of THF4 –> no thymidine
- folate stuck in N5-methylTHF4 (methyl trap)
- pathologic changes in nervous system (spinal cord) –> motor and sensory deficits**
- usually no dietary insufficiency (long stores)**
10
Q
how can you get B12 deficiency?
A
- pernicious anemia** –> autoimmune gastritis that impairs intrinsic factor
- autoreactive T cells against parietal cells** –> trigger autoantibodies
- increased risk of gastric carcinoma
- CNS deficits like demyelination of spinal cord –> paresthesia and ataxia
- need to replace B12
11
Q
megaloblastic anemia - folic acid deficiency
A
- modest reserves –> deficiency faster than B12**
- due to decreased intake or increased requirements –> pregnancy, infancy, age, hemolytic anemia
- methotrexate can reduce THF4
- no neurologic symptoms like B12**
- make neurologic symptoms worse if already B12 deficient** (give B12 1st before folate treatment**)
12
Q
microcytic anemias
A
- Fe deficiency most common cause –> due to diet, impaired absorption, increased requirement, blood loss
- no Fe –> no Hb –> no RBC
- rule out GI cancer with chronic bleeding
13
Q
Fe metabolism
A
- absorbed in duodenum (after being reduced to Fe2+/ferrous by stomach acid)
- stores increase –> absorption decreases
- hepcidin (liver protein) regulates Fe transport from duodenum to blood –> inhibits ferroportin1 to prevent transport when Fe stores are full & vice versa**
- Fe stores low –> hepcidin low**
- transported by plasma transferrin** –> liver and marrow
- stored as ferritin in marrow** (hemosiderin in excess) –> liver and mononuclear phagocytes (spleen, marrow)
- ferritin in blood/tissue; hemosiderin in tissue only
- used to make Hb of RBCs
- degraded by Macs 120 days in spleen, liver, marrow
14
Q
microcytic anemia - Fe deficiency
A
- cause: impaired absorption, high requirement, blood loss
- microcytic, hypochromic (less Hb)**
- deplete Fe stores –> low serum Fe, ferritin, high transferrin
- Hb and hematocrit are low
- central pallor enlarged
15
Q
microcytic anemia - thalassemia syndrome
A
- causes hemolytic anemia
- gene deletion and mutation –> unstable Hb –> precipitate causing membrane damage –> anemia, hypoxia, hemolysis
- HbA (a2b2), HbF (a2, gamma2)
- unbalanced chains recognized in bone marrow and phagocytosed –> ineffective erythropoiesis
- microcytic, hypochromic cells
- target cells and fragmented cells; spleen removes inclusions
- crew cut appearance on X rays**
- splenomegaly (due to phagocytosis and extramedullary hematopoiesis)
16
Q
alpha thalassemia syndrome
A
- deficient alpha chains (deletions)
- 4 genes, chromosome 16
- less severe than beta thalassemia
- unpaired beta globin chains form precipitates
- abnormal pairing of beta and gamma chains
- delete single alpha gene (silent carrier) –> asymptomatic –> slight microcytosis
- 2 genes (alpha thalassemia trait) –> like beta thal. minor, minimal anemia
- 3 genes (HbH from beta globin tetramers) –> hypoxia, inclusions, phagocytosis, severe anemia
- 4 genes (hydrops fettles from gamma globin tetramers; Hb Barts) –> hypoxia, edema, hepatosplenomegaly
17
Q
beta thalassemia syndrome
A
- deficient beta chains (mutations)
- 2 gene, chromosome 11
- B0 (absent beta globin synthesis), B+ (reduced synthesis)
- unpaired alpha globin chains form precipitates, inclusions –> membrane damage
- heterozygote (1 mutated gene) –> mild microcytic anemia (b thalassemia minor)
- 2 mutated genes –> severe ineffective erythropoiesis, erythroid hyperplasia in marrow, extra medullary hematopoiesis, transfusion dependent (b thalassemia major)
- rare combinations of gene mutations –> moderate anemia (b thalassemia intermedia)
18
Q
anemia of chronic disease
A
- chronic inflammation –> IL-6 –> increased hepcidin production**
- chronic anemia bc ferroportin1 is inhibited –> no Fe transport to blood (remains stored in Macs)
- reduced proliferation of erythroid progenitors and Fe utilization
- maybe protection to defend against infection
- increased storage in marrow macrophages, high serum ferritin rules out Fe deficiency
19
Q
normocytic anemias - acute blood loss
A
- loss of intravascular volume (ex. GI bleed) –> shock
- interstitial fluid restores volume diluting hematocrit (value decreases)
- low O2 –> EPo release from kidneys –> stimulate erythroid progenitors
- leukocytosis due to adrenergic increase in WBCs –> toxic granulations and Dohl bodies
20
Q
hemolytic anemias
A
- due to extravascular or intravascular hemolysis
- destruction of red cells due to surface proteins or phagocytosis in macrophages
- anemia if lifespan is <120 days
- accumulate Fe and hemosiderin
- increased EPO and serum bilirubin levels**
- increased reticulocytes
- extramedullary hematopoiesis if necessary
21
Q
extravascular hemolysis
A
- premature red cell destruction by Macs in spleen, marrow, liver
- treat with splenectomy
- see anemia, jaundice, splenomegaly
22
Q
intravascular hemolysis
A
- less common
- due to mechanical injury (heart valve), complement (antibody mediated), parasites (malaria), and toxins
- destroy RBCs within vessel
- anemia, hemoglobinuria, hemoglobinemia, jaundice (no splenomegaly)
- haptoglobin depleted after it binds Hb then degraded by Macs
23
Q
hemolytic anemia - trauma induced
A
- normocytic
- mostly due to cardiac valves prosthesis or microangiopathic hemolytic anemia (MAHA)**
- MAHA seen with DIC, TTP, HUS, hypertension, SLE, and cancer
- MAHA causes lesion and fibrous strands –> luminal narrowing –> produce schistocytes**
24
Q
hemolytic anemia - hereditary spherocytosis
A
- normocytic, autosomal dominant
- extravascular hemolysis
- get anemia, splenomegaly, jaundice, bilirubin gallstones
- defective RBC membrane proteins –> form spherocytes** becoming less deformable –> destroyed by spleen
- anemia corrected with splenectomy
- spherocytosis –> produce Howell-Jolley bodies (DNA fragments)**
- cells swell/burst with osmotic lysis hypotonic solution**
25
Q
hemolytic anemia - sickle cell
A
- normocytic
- extravascular hemolysis
- mutation of beta globin (glutamate –> valine) forming HbS
- causes RBC distortion, anemia, microvascular obstruction, and ischemic tissue damage
- heterozygote for HbS (sickle cell trait) –> protection against P. falciparum malaria**
- pathology: cytosol converted to viscous gel –> needle like fibers in red cell from HbS
- cells become dehydrated, rigid, non deformable, deoxygenated –> more sickling
- form target cells, Howell-jolley Bodies, splenomegaly/infarction/autosplenectomy
- acute chest syndrome**
- aplastic crisis –> parvovirus B19 infection**
- susceptible to encapsulated organisms (pneumonia and H. influenza)
26
Q
hemolytic anemia - G6PD deficiency
A
- normocytic, X linked
- intravascular hemolysis
- deficiency in G6PD –> cannot make NADPH for GSH –> oxidative stress to older RBC
- oxidative stress by: infection, antimalarials, sulfonamides, fava beans –> cross link globin chains and form Heinz bodies** (remnants of precipitated Hb)
- spleen degrades RBCs that have oxidants –> produce bite cells**
27
Q
hemolytic anemia - hemoglobin C (HbC)
A
- normocytic
- extravascular hemolysis
- B globin mutation (glutamate –> lysine)**
- sickling due to HbSC is milder than sickle cell disease
- target cells on histo**
28
Q
hemolytic anemia - Paroxysmal nocturnal hemoglobinuria (PNH)
A
- normocytic, X linked disease of HSC origin
- intravascular hemolysis
- mutations in PIGA gene of GPI anchor proteins**
- absence of GPI anchor proteins, CD55, and CD59** –> uncontrolled complement activation (C5b-C9)**
- causes hemolyis, thrombosis, and cytopenias
- occurs at night due to decrease in blood pH activating complement
- thrombosis leading cause of death**
29
Q
hemolytic anemia - immune hemolytic anemia (IHA)
A
- normocytic
- intravascular hemolysis
- antibodies bind to RBCs –> premature destruction
- IgM antibodies agglutinate cells
- indirect (Coombs) antiglobulin test –> detect antibody in patient’s serum**
- direct (Coombs) antiglobulin test –> detects antibody attached to patient’s RBC –> agglutination if antibody is on surface
- in autoimmune hemolytic anemia, there is alloantibody is against blood antigen that is not on RBC –> warm antibody type most common and is usually IgG extravascular hemolysis
30
Q
polycythemia
A
- abnormally high red cell count that increases Hb levels
- relative –> decreased volume (dehydration) concentrating the Hb
- absolute –> increased RBC mass from gene mutation or increased EPO due to lung disease
- polycythemia vera most common cause of primary polycythemia –> mutations lead to EPO independent growth of progenitor cells
