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ch 5 pathoma notes - anemia
Terms in this set (95)
in microcytic anemia what is the reason all the rbcs are small?
heme made of
Fe + protoporphyrin
iron absorption where/how/transported by what
what happens when ferretin levels go down?
TIBC goes up
stages of fe def
lab findings fe def
FEP: free erythrocyte protoporphyrin
associated sydrome that comes with iron def anemia
how does chronic dz lead to anemia?
chronic dz anemia lab findings
sideroblastic anemia cause?
defect in protoporphyrin synth
sideroblastic anemia - where is the iron buildup located?
in the mitochondria
sideroblastic anemia - congenital and acquired causes
congenital: ALAS defect
acquired: B6 def, lead poisoning, etoh
what tx can cause b6 def?
sideroblastic anemia - lab findings
why are people carriers of thalassemia
carriers are protected against
plasmodium falciparum malaria
types of thalassemia
how many alpha genes do we have, and what chromosome?
4 alleles on chromosome 16
what is the problem in alpha thalassemia
cis deletion vs trans deletion alpha thalassemia
two gene deletion
cis is worse - two gene deletion on the same chromosome, increased risk of severe thalassemia in offspring
trans - two deletions on opposite chromosommes
cis configuration implies a horizontal orientation just like the wide horizontal Asia continent
trans configuration implies vertical orientation just like the tall and narrow African continent
alpha thalassemia: 1 deletion, 2 deletions, 3 deletions, 4 deletions
2 genes: increased RBC count
3 gene: Hbh, a beta tetramer, can be cis or trans
4 gene: Hemoglobin Barts = in utero gamma tetramer: aka
beta thalassemia due to
how many genes?
MUTATION not deletions (like alpha)
beta thalassemia minor
Beta Thalassemia minor blood smear and electrophoresis would show?
an increased RBC count.
microcytic, hypochromic RBCs and target cells are seen on blood smear (Fig.
electrophoresis shows slightly decreased HbA with increased HbA2 and HbF
beta thalassemia major hemoglobin type
not fatal for babies, but produces alpha tetramers
beta thalassemia major causes what kind of hemolysis
Unpaired alpha chains precipitate and damage RBC membrane, resulting in ineffective erythropoiesis and extravascular hemolysis
*Chronic transfusions are often necessary; leads to risk for secondary hemochromatosis
What other physical effects does beta thal have on the body?
-Massive erythroid hyperplasia ensues resulting in expansion of hematopoiesis into the skull
= bone deformation and hepatosplenomegaly
what infection would be highly risky in setting of b thal?
risk of aplastic crisis with parvovirus B19: an infection of erythroid precursors.
beta thalassemia major blood smear and electrophoresis would show
Smear shows microcytic, hypochromic RBCs with target cells and nucleated red blood cells.
Electrophoresis shows HbA, and HbF with little or no HbA.
target cells seen in?
3 gene deletion alpha thalassemia
and beta thalassemias
lack of folate/b12 causes
megaloblastic anemia with hypersegmented neutrophils
megaloblastic change in other rapidly dividing cells
other causes of macrocytic anemia that are not b12/folate def? difference between them and b12/folate def?
drugs (ie 5-FU)
-no megaloblastic change in other rapidly dividing cells
-no hypersegmented neutrophils
folate absorbed from where
folate def caused by?
folate def: blood smear, physical sx, and lab values?
r-binder by saliva
, then cleaved by
proteases, and bound by
of stomach parietal cells, absorbed in
autoimmune destruction of parietal cells (stomach)--> IF def---> no b12 absorbtion
most common cause of b12 def
other causes of b12 def?
ilium damage 2/2 crohn's or diphyllobothrium latum
clinical findings of b12 def
lab findings of b12 def
The corrected reticulocyte count =
Hct = hb x 3 =
corrected reticulocyte count = ( Hct/45 ) x reticulocyte count
Extravascular hemolysis: Macrophages consume RBCs and break down hemoglobin:
Globin is broken down into________
Heme is broken down into ___________
iron is ___.
globin--> amino acids.
heme--> iron and protoporphyrin
Protoporphyrin is broken down into ___________, which is bound to__________ and delivered to_________________________
the liver for conjugation and excretion into bile
Clinical and laboratory findings: Extravascular hemolysis
Anemia with splenomegaly,
jaundice due to unconjugated bilirubin
increased risk for bilirubin gallstones
high reticulocyte count
what is the first step of intravascular hemolysis?
hemoglobin spills into blood, is bound by haptoglobin
what are clinical/lab signs of intravascular hemolysis
Hemosiderinuria—(Renal tubular cells pick up some of the hemoglobin that is filtered into the urine and break it down into iron, which accumulates as hemosiderin; tubular cells are eventually shed resulting in hemosiderinuria.
Decreased serum haptoglobin)
extravascular hemolysis diseases
sickle cell anemia - mostly extravasc, a lil intra
what is it? what proteins does it commonly involve
Inherited defect of RBC cytoskeleton-membrane tethering proteins - consumed by splenic macrophages, resulting in anemia.
1. Most commonly involves ankyrin, spectrin, or band 3
HS laboratory findings include
Spherocytes with loss of central pallor
increaed RDW and T mean corpuscular hemoglobin concentration (MCHC)
HS clincial findings + increased risk for what?
Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones (extravascular hemolysis)
Increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors
HS diagnosed by?
osmotic fragility test
HS treated by? what are the impacts of treatment?
Treatment is splenectomy; anemia resolves, and
Howell-Jolly bodies emerge
(fragments of nuclear material in RBCs)
sickle cell anemia mutation and inheritance
what does it protect against
AR glutamic acid--> valine
against falciparum malaria.
Need two abnormal beta genes
when do the cells become sickle shaped
in hypoxemia, dehydration, acidosis
the hemoglobin polymerizes
when is onset of sickle cell sx?
~6mo, bc HbF is protective
Treatment with _________increases levels of HbF.
Treatment with hydroxyurea increases levels of HbF.
What kind of hemolysis in sickle cell dz?
Extravascular hemolysis—Reticuloendothelial system removes RBCs with damaged membranes, leading to
Intravascular hemolysis—RBCs with damaged membranes dehydrate, leading to hemolysis
Effects of the Extravascular hemolysis + Intravascular hemolysis:
Extravascular hemolysis: anemia, jaundice with unconjugated hyperbilirubinemia, bilirubin gallstones.
Intravascular hemolysis: decreased haptoglobin, target cells
What does all this hemolysis lead to in sickle cell anemia? what is a major infection risk?
Massive erythroid hyperplasia : extramedullary hematopoiesis with hepatomegaly
Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
What are problems caused by irreversible sickling?
complications of vaso-occlusion:
1. Dactylitis—swollen hands/feet due to infarcts in bones; common in infants
2. Autosplenectomy—shrunken, fibrotic spleen:
risk of infections, Howell-Jolly bodies on blood smear
3. Acute chest syndrome—vaso-occlusion in pulmonary microcirculation
4. Pain crisis
5. Renal papillary necrosis—results in gross hematuria and proteinuria
Sickle cell disease vs Sickle cell trait
Sickle cell disease: two abnormal Beta genes
Sickle cell trait: one mutated and one normal Beta chain
What is a complication of sickle cell trait, even though most patients are asymptomatic?
Extreme hypoxia and hypertonicity of the medulla cause sickling, which results in microinfarctions leading to microscopic hematuria and, eventually, decreased ability to concentrate urine.
Laboratory findings of sickle cell disease and sickle cell trait
Sickle cells and target cells in sickle cell disease. NOT in sickle cell trait tho.
Hb electrophoresis for HbS in both dz and trait
______________screen causes cells with any amount of HbS to sickle; positive in both disease and trait
Hemoglobin C - what is it?
~HbC has lyCeen~
AR mutation in Beta chain of hemoglobin: glutamic acid --> lysine.
Presents with mild anemia due to extravascular hemolysis
Characteristic HbC crystals are seen in RBCs
what are the predominantly intravasular hemolysis anemias?
paroxysmal nocturnal hemoglobinuria
immune hemolytic anemia - IgM only!
what is paroxysmal nocturnal hemoglobinuria
defect in myeloid stem cells (RBCs, WBCs, and platelets);
absent glycosylphosphatidylinositol (GPI)
= susceptible to destruction by complement
Decay accelerating factor (DAF) inhibits C3 convertase. DAF anchored by GPI
why does paroxysmal nocturnal hemoglobinuria occur at night
Mild respiratory acidosis develops with shallow breathing during sleep and activates complement.
What are sx of paroxysmal nocturnal hemoglobinuria
Intravascular hemolysis leads to:
hemoglobinuria (especially in the morning); hemosiderinuria days after hemolysis
____ test is used to screen for paroxysmal nocturnal hemoglobinuria
confirmatory test is _______?
Sucrose test is used to screen for disease;
confirmatory test is the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells.
Main cause of death due to PNH is what? and why?
Main cause of death is thrombosis of the hepatic, portal, or cerebral veins.
Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis.
two major complication of PNH are
-iron deficiency anemia (due to chronic loss of hemoglobin in the urine)
-acute myeloid leukemia (AML), which develops in 10% of patients.
G6PD def - what is it, inheritance
X-linked recessive disorder
reduced half-life of G6PD; renders cells susceptible to oxidative stress since NADPH
, a by-product of G6PD, is needed to regenerate reduced glutathione-»intravascular hemolysis
G6PD deficiency has two major variants.
1. African variant—mildly reduced half-life of G6PD leading to mild intravascular hemolysis with oxidative stress
2. Mediterranean variant—markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress
*protective role against falciparum malaria.
in G6PD def, oxidative stress causes precip. of hemoglobin as _____________, which leads to
removal of HBs by spleenic macrophages, resulting in
--> intravascular hemolysis
hemoglobinuria + back pain (since hb is nephrotoxic)
when would you do an enzyme study in G6PD def
AFTER hemolysis resovles, otherwise all cells w/o the enzyme will have been lysed
immune hemolytic anemia types
IgG or IgM mediated destruction of RBCs
IgM- intravascular hemolysis COLD
IgG - extravascular hemolyis WARM
IgG is usually ____________ hemolysis
IgM is usually ___________ hemelysis
IgG-mediated: extravascular hemolysis.
IgM-mediated: intravascular hemolysis
IgG, bites of membrane taken out by splenic macrophages-->
(presents the same as hereditary spherocytosis)
what diseases are IgG immune hemolytic anemia associated with?
SLE, CLL (chronic lymphocytic leukemia)
How to to treat IgG immune hemolytic anemia
IvIG (to distract spleen, buys time), steroids, splenectomy
IgM-mediated: IgM binds RBCs and ___________
Associated with ____________ (2 infections)
fixes complement in cold extremities
How to diagnose immune hemoyltic anemia?
Coombs test is used to diagnose IHA; testing can be direct or indirect.
Coombs test: direct vs indirect
1. Direct Coombs test for: antibody-coated RBCs. Anti-IgG is added to patient RBCs; agglutination occurs if RBCs are ALREADY coated with antibody. This is the most important test for IHA.
2. Indirect Coombs test: antibodies in patient SERUM. Anti-IgG and test RBCs are mixed with the patient serum; agglutination occurs if serum antibodies are present.
microangiopathic hemolytic anemia
Intravascular hemolysis that results from vascular pathology; RBCs are destroyed as they pass through the circulation. = SCHISTOCYTES
Iron deficiency anemia occurs with chronic hemolysis,
B. Occurs with microthromhi (TTP-HUS, DIG, HELLP), prosthetic heart valves, and
aortic stenosis; microthrombi produce schistocytes 011 blood smear (Fig. 5.13),
diseases/conditions that result in microangiopathic hemolytic anemia
TTP and HUS and DIC
prosthetic heart valves, and aortic stenosis; microthrombi produce schistocytes
Malaria - bacteria name, and vector species?
Infection of RBCs +liver with Plasmodium; transmitted by the female Anopheles mosquito
what causes the hemolysis in malaria and where?
RBCs rupture as a part of the Plasmodium life cycle, resulting in intravascular hemolysis and cyclical fever.
Spleen also consume s some infected RBCs; results in mild extra vascular hemolysis with splenomegaly
which malarial strains cause daily fever, and which cause every other day faver
Jvivax and P ovale—fever every other day
Anemias due to undproduction: types
parovirus b19 - infection of precursor RBCs
renal failure - decreased production of EPO
aplastic anemia - damage to HSC
Lab values for underproduction anemia
Decreased production of RBCs by bone marrow; characterized by low corrected reticulocyte count
underlying causes of underproduction anemia
Almost ANY microcytic and macrocytic anemia
Renal failure—decreased production of EPO by peritubular interstitial cells
Damage to bone marrow precursor cells (may result in anemia or pancytopenia)
what is it
Pathologic process (e.g., metastatic cancer) that replaces bone marrow; hematopoiesis is impaired, resulting in pancytopenia.
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