Flashcards in Chapter 14: Red Blood Cells Deck (91)
What are the Mean Cell Volume, Mean Cell Hemoglobin, Mean Cell Hemoglobin Concentration, and Red Cell Distribution Width values?
MCV: average volume of red blood cells
- normal = 80-100
MCH: average mass of hemoglobin per RBC
- changes RBCs color
MCHC: average hemoglobin concentration in a given volume of RBCs
RDW: coefficient of variation of red blood cell volume
- elevation --> reactive phenomenon in anemia
- have FUNCTIONING marrow
What is hematocrit?
ratio of packed RBCs to total blood volume
**approximately 3x the hemoglobin concentration**
If a male or postmenopausal women is found to be chronically bleeding, what should it be assumed that patient has until proven otherwise?
What is Hemolytic Anemia and what does it look like morphologically? (3)
RBC lifespan less than 120 days, with inc. in EPO and accumulation of hemoglobin degradation products
Morph: inc. normoblast in marrow, reticulocytosis in peripheral blood, hemosiderosis
What is the difference between Extravascular and Intravascular Hematopoiesis?
EH: occurs in macrophages of spleen (predisposed by RBC injury)
- anemia, splenomegaly, jaundice
- splenectomy is often beneficial
IH: RBC rupture due to mechanical injury, complement, parasites, or toxins
- hemoglobinuria, hemosiderinuria (NO splenomega)
- markedly reduced serum haptoglobin (a2 globulin)
- renal hemosiderosis
**haptoglobin normally prevents hemoglobin excretion in urine**
What is it, how is it inherited, and what is its pathogenesis?
- defects of RBC membrane skeleton causing cells to become spheroid and less deformable
- 75% autosomal dominant, mostly prevelant in Northern Europe
- mutations of ankyrin, band 3, band 4.2, and spectrin (RBCs destroyed by spleen in 10-20 days)
What does it look like (3) and how is it diagnosed?
M: small, dark RBCs w/o central pallor zone, reticulocytosis, and cholelithiasis (pigment stones in 40-50% of pts)
D: history, hematology findings, and labs
- osmotic fragility test, inc. MCHC
How does it present clinically (4) and how is it treated?
C: variable anemia, splenomegaly, jaundice, gallstones
- inc. risk of aplastic crisis due to Parovirus B19
- stops hematopoiesis for a couple of weeks
T: splenectomy (corrects anemia but Howell-jolly bodies remain)
- inc. risk of sepsis (encapsulated bacteria)
What are the two types, what are their genetics, and what is happening?
G6PD- (African Americans, less severe) and G6PD Mediterranean (more severe, shorter enzyme 1/2 life)
- oxidants cause crosslinking of globin chains causes precipitates (Heinz bodies) which are removed by macrophages, creating "bite cells"
**older RBCs more prone to hemolysis; younger RBCs not affected**
What causes oxidative stress on G6PD? (FASN)
fava beans, antimalarial drugs (quines), sulfonamides, nitrofurantoins
Sickle Cell Anemia:
What mutation is it caused by and what four things are likely to decrease the rate of sickling?
- hereditary hemoglobinopathy via glutamate --> valine mutation in beta-globulin (microvascular obstruction most serious feature)
- Hb forms RBC polymers when deoxygenated, forming long needlelike fibers
Dec. sickling: inc. HbA, dec. MCHC/hydration, inc. pH, inc. microvascular transit
What are HbSC (Sickle Cell Disease) and Fetal Sickle Cell Anemia?
HbSC - compound heterozygotes (HbS and HbC genes) --> milder than sickle cell anemia
- glutamic acid --> lysine (crystals on smear)
- causes extravascular hemolysis
Fetal SC - have more HbF (protective), so problems often present at 6 months old
- hydroxyurea enhances HbF expression
What is the process of Sickle Cell Stasis?
- inc. adhesion molecules (inflammation) cause cells to arrest while moving through microvasculature
- inc. sickling and obstruction lead to hypoxia
- free hemoglobin binds and inactivates NO = inc. vascular tone and inc. platelet aggregation
Sickle Cell Anemia:
What is Autosplenectomy, Vasoocclusive Crises, Sequestration Crisis, Aplasic Crisis, and what bone problems are seen?
AS: chronic erythrostasis causes splenic infact and fibrosis
VC: MOST IMPORTANT COMPLICATION
- hypoxic injury/infarction episodes cause pain
- manifests as dactylitis or acute chest syndrome
- hard to differentiate from Acute Osteomyelitis
SC: massive entrapment of RBCs in kids spleen
- rapid enlargment, hypovolemia, shock
AC: Parovirus B19 infection dec. hematopoiesis
bones: marrow expansion = remodeling
- "Chipmunk" cheeks, prominent cheek bones
- skull changes resembling "crew cut"
Sickle Cell Anemia:
What is Dactylitis and Acute Chest Syndrome?
- manifestations of Vasoocclusive Crisis
D: hand-foot syndrome
- vasoocclusive infarcts = swollen hands/feet
- seen in African America infants
ACS: vasooclusive crisis of lungs
- most common cause of death in adult pts
- often precipitated by pneumonia
What is the most common cause of death in children with Sickle Cell Anemia?
- causes septicemia and meningitis
What 4 pathogens are pts with Sickle Cell Anemia more at risk for?
S. pneumoniae, H. influenzae, neisseria (encaspsulated)
- inc. risk of S. Typhi osteomyelitis
How is Sickle Cell Anemia diagnosed, what is its prognosis, and how can it be treated (2)?
D: clinical signs/symptoms, lab testing of hemoglobin
- metabisulfite screen (+)
P: 90% survive to 20, 50% survive to 50+
T: hydroxyurea (inc. HbF) and HSC transplant
What is the difference between Beta0 and Beta+ in Beta Thalassemia?
What is the pathogenesis of Beta Thalassemia?
Beta0 - absent beta globin chain synthesis
- most common mutation is premature STOP codon
Beta+ - reduced but detectable bet globin synthesis
- most common mutation is splicing
P: unpaired alpha chain preceiptates, creating insoluble inclusions = membrane damage = APOPTOSIS of precursors
What are manifestations that occur in severe cases of Beta Thalassemia? (4)
- massive erythroid hyperplasia; extramed. hematoe
- "crew cut" and "chipmunk" facies
- severe cachexia, iron overloading causing SECONDARY hemachromatosis
What cell changes are seen on peripheral smear of Beta Thalassemia? (4)
anisocytosis (variable size), poikilocytosis (variable shape), target cells (hemoglobin in center), and basophilic stippling
Beta Thalassemia Major:
Who is it most common in (3) and what Hb type is most prominent?
- individuals have transfusion dependent anemia beginning at 6-9 months
- Mediterranean, Africa, Southeast Asia
- HbF hemoglobin is predominant
Beta Thalassemia Major:
What are 4 clinical impacts of disease and what are two major treatment options?
- hepatosplenomegaly (hematopoiesis), massive erythroid hyperplasia, possible aplastic crisis
T: chronic transfusions (3rd decade survival)
- predisposed to 2nd hemachromatosis
- HSC transplant may occur
Beta Thalassemia Minor:
What is it, what does it cause (4), and what Hb type is most prominent?
What anemia must be ruled out if you believe your pt. has Beta Thalassemia Minor?
- individuals with heterozygous alleles (MORE COMMON)
- mild microcytic, hypochromic anemia, basophilic stippling, target cells, and erythroid hyperplasia
- HbA2 hemoglobin is predominant
**confirm diagnosis to rule out IRON DEFICIENCY ANEMIA**
What is it, how does it differ from Beta Thalassemia clinically, and what are its 4 types?
- inherited gene deletion causing absent or reduced alpha-globin chains
- beta and gamma chains are more soluble, meaning less severe hemolysis and ineffective erythropoiesis
types: Silent Carrier, a-thalassemia trait, Hemoglobin H disease, Hydrops Fetalis
What is the Silent Carrier Type?
- deletion of single gene causing barely detectable reduction in synthesis
What are the two alpha-thalassemia deletions and what disease is it clinically similar to?
- Cis deletion: two genes deleted on 1 chromosome
- common in Asians, offspring at inc. risk of disease
- Trans deletion: one gene deleted from both chromo
- common in African Americans
- microcytosis w/minimal anemia
**clinically similar to B-thalassemia Minor**
What is the Hemoglobin H Disease and what disease is it clinically similar to?
- 3 gene deletion common in Asians, creates HbH
- Beta tetramers form w/inc. oxygen affinity, causing tissue hypoxia disproportionate to lvl of Hb
- does NOT require transfusions
**resembles B-thalassemia Intermedia**
What is Hydrops Fetalis and what does it cause?
- deletion of all 4 genes, creates Hemoglobin Barts (gamma globin tetramer w/greatly inc. oxygen affinity)
- causes Fetal Distress Syndrome beginning 3rd trimester (requires lifelong transfusions)
**HSC is curative**