RBC Pathology 1 Flashcards
What is the basic definition of anemia?
A reduction of the total RBC mass below normal limits. It diagnosed using Hct. and Hb concentration.
What is the definition of the following?
Mean cell volume
Mean cell hemoglobin
Mean cell hemoglobin concentration
Red cell distribution width
Mean cell volume: the average volume of a red cell in fL.
Mean cell hemoglobin: the average content (mass) of hemoglobin per red cell in pG.
Mean cell hemoglobin concentration: the average concentration of hemoglobin in a given volume of packed red cells in g/dL.
Red cell distribution width: the coefficient of variation of red cell volume.
What is the clinical presentation of a patient with anemia?
They may appear pale, weak, malaised and easily fatigued with DOE.
The chronic hypoxia may result in fatty change in the liver, myocardium and kidneys.
The effects of acute blood loss are mainly due to what?
If the bleed is large enough to decreased BP, what compensatory changes occur?
What is the major concern during recovery of the bleed?
The loss of intravascular volume, which if massive, can lead to cardiovascular collapse, shock and death.
If the bleed is significant enough to lower BP, there will be mobilization of granulocytes (leukocytosis) and elevated reticulocyte ct.
During early recovery, thrombocytosis occurs and may lead to clots.
How long does it take for reticulocytes to be produced after an acute bleed?
5-7 days
What 3 features are noticed in hemolytic anemias?
Shortened RBC lifespan below the typical 120 days.
Elevated EPO levels and a compensatory increase in erythropoiesis.
Accumulation of RBC products due to hemolysis.
Chronic anemia is induced only when:
The rate of loss exceeds the regenerative capacity of the marrow (1) or when iron reserves are depleted (2) and iron-deficiency anemia appears.
What is the major cause of extravascular hemolytic anemia?
What are the typical signs/symptoms? (3)
Lack of deformability of red cells in the sinusoids.
Anemia, splenomegaly and jaundice.
What can cause intravascular hemolytic anemia?
What are the typical signs/symptoms? How can it be differentiated from the extravascular type?
Mechanical injury, complement activation, intracellular parasites or toxins.
Anemia, hemoglobinemia, hemoglobinuria and jaundice. Splenomegaly is typically NOT a feature (it is in extravascular anemia)!
What is the role of haptoglobin (“suicide molecule”)?
It binds free Hb to prevent its excretion in urine. It is used to measure the amount of free Hb. It is decreased in hemolytic anemias.
What kind of BR is elevated in uncomplicated hemolytic anemias?
Unconjugated BR
What do the red cells look like in hereditary spherocytosis (HS)?
The RBC cell membrane skeleton is affected and renders the red cells spherical, less deformable and vulnerable to splenic sequestration and destruction.
What is the inheritance pattern of hereditary spherocytosis?
RBCs in HS are abnormally sensitive to what?
What lab finding is elevated in HS?
AD (75%)
Osmotic lysis when incubated in hypotonic solutions.
Mean cell Hb concentration (MCHC) is elevated.
What are the symptoms of HS?
What is the clinical progression of HS?
What can be done to treat the anemia and its complications?
Anemia, splenomegaly and jaundice. In about 25% of patients the disease is asymptomatic; in the remaining 75%, compensatory changes are outpaced producing a chronic hemolytic anemia of mild to moderate severity. Gallstones may occur also.
It is generally stable, but sometimes punctuated by aplastic crises, often triggered by an acute parvovirus infection, due to increased splenic destruction.
Splenectomy treats the anemia and its complications, but increases the risk of sepsis (spleen filters blood-borne bacteria).
What is the biochemical consequence of glucose-6-phosphate dehydrogenase deficiency?
What is the inheritance?
What is the characteristic of G6PD deficiency?
G6PD reduces NADP to NADPH, which goes on to create reduced glutathione which helps in protecting against oxidant injuries.
X-linked recessive.
Episodic hemolysis caused by exposures that generate oxidant stress, most often due to infection (hepatitis, pneumonia and typhoid fever). Certain drugs and foods ma also induce this stress.
What do the RBCs in G6PD look like on a smear?
What symptoms ensue after exposure to an oxidant?
Which patients may have a greater degree of hemolysis?
They appear as “bite cells” because splenic macrophages pluck out Heinz bodies (precipitates of denatured globin).
Acute intravascular hemolysis, marked by anemia, hemoglobinemia and hemoglobinuria 2-3 days post exposure to oxidants.
The hemolysis is greater in individuals withe highly unstable G6PD Mediterranean variant.
Which globin chains are produced before birth and into the post-natal period?
Which globin chains are produced in smaller quantities before birth, but begin to increase shortly before birth?
Which globin chains are produced before birth, but taper off around week 24?
Which globulin chains are produced beginning at birth only, and are produced in a small quantity?
Alpha
Beta
Gamma
Delta
What are the following lab values in males vs. females?
Hb (g/dl)
Hct.
RBC ct. (x 1 million)
Hb (g/dl): 13.6-17.2 (M), 12.0-15.0 (F).
Hct.: 39-49% (M), 33-43% (F).
RBC ct. (x 1 million): 4.3-5.9 (M), 3.5-5.0 (F)
What is the inheritance of sickle cell disease (SSD)?
What is the mutation?
What occurs to the RBC as a result?
AR
A point mutation in the beta-globin that leads to polymerization of deoxygenated Hb (Glu is replaced with Val).
There is RBC distortion, hemolytic anemia, microvascular obstruction and ischemic tissue damage.
What is seen on microscopy in patients with SSD? (3)
Sickled cells
Anisocytosis (unequal size)
Poikilocytosis (abnormal shape).
What lab changes are seen in SSD? (4)
What signs/symptoms may exist in SSD? (5)
What tends to be the most common symptoms in kids?
Severe hemolytic anemia (18-30%), reticulocytosis and elevated BR, depleted NO by haptoglobin.
Vaso-occlusive crises causing severe pain (bone, lungs, liver, brain, spleen and penis).
Acute chest syndrome (vaso-occlusive crisis in the lungs) - cough, fever, CP and infiltrates.
Priapism - hypoxic damage and ED.
Stroke
Retinopathy
Severe bone pain that is hard to differentiate from osteomyelitis.
In kids with SSD and a spleen, what “crisis” may occur?
An aplastic crisis in SSD stems from what?
What 2 processes may cause death acutely in SSD?
What is responsible for generalized impairment of growth and development in SSD?
Aside from what is listed, what else is a major threat in SSD?
Sequestration crisis - a massive entrapment of sickled RBCs leads to rapid splenic enlargement, hypovolemia and possible shock.
Infection of RBC progenitors by parvovirus B19.
Sequestration crisis and acute chest syndrome.
Chronic hypoxia.
Infection by encapsulated organisms, commonly S. pneumoniae and H. flu.
What is used to diagnose HbS and rule-out other hemoglobinopathies?
How is SSD diagnosed prenatally?
Hemoglobin electrophoresis.
Analysis of fetal DNA by amniocentesis or chorionic biopsy.
What are symptoms of hemoglobin C disease?
What are the symptoms of hemoglobin SC disease?
What alleles are affected in hemoglobin C disease?
How does this differ from hemoglobin SC disease?
Hb C disease: typically asymptomatic. It may exhibit mild (chronic) hemolytic anemia and the sequelae associated with it.
Hb SC disease: it is a symptomatic sickling disorder.
Hb C disease: both beta chains are affected (2-3% in AAs).
Hb SC disease: only one beta chain is affected (8% of AAs), thus it much more common.
What chromosome codes the 2 alpha-chains? How many genes?
What chromosome codes the 2 beta-chains? How many genes?
Chr. 16 - 2 alpha-globin genes.
Chr. 11 - 1 beta-globin gene.
What causes the hematologic consequences in thalassemias?
Both the deficiency of the globin chain involved and the excess of the other chain (i.e. a-thalassemia leads to decreased [alpha-chain] and elevated [beta-chain]).
