Lecture 5.1 MJ slides Flashcards
1) RBC’s live ______ days in RBC destruction, the life span is shortened
2) RBC’s are being ________ when they die; this leads to the release of ________________
3) Why is this thing released?
1) 120
2) lysed; unconjugated bilirubin
3) The bili wasn’t able to be conjugated through normal delivery to the liver
What does hemolysis lead to? What should you check?
1) Hemolysis > low 02 > increased EPO > increased reticulocytes being made
2) Therefore, check the reticulocyte count; it will be high in this disease
What are 2 ways to classify the cause of hemolysis?
Intravascular and extravascular
Extravascular hemolysis:
1) What causes it?
2) Where does this often happen, and why does this happen there?
1) Defects that destroy the RBCs with phagocytes
2) Spleen; requires that cells be able to change their shape in order to move through it; when they cannot, they get stuck. This is called “sequestration”
Define sequestration
A process by which the spleen traps cells with diminished deformability and feeds them to macrophages
List 3 findings in extravascular hemolysis
1) Hyperbilirubinemia and jaundice
2) Late-stage, gallstones and cholelithiasis
3) Sometimes splenomegaly
What is the pathway of hemolysis?
1) RBC houses Hgb
2) Hgb breaks down inside cell releasing bili as byproduct + disease causes RBC to not be pliant
3) RBCs stuck in spleen
4) Spleen houses macrophages for just such a purpose
5) Degradation of RBCs lets unconjugated bili into bloodstream
6) Over time, jaundice and gallstones can occur, as can splenomegaly
Intravascular hemolysis:
1) What is it? What can cause it?
2) What does this release? Explain
1) Direct insult to RBC that bursts in the blood stream
-Turbulence from defective heart valve, complement destruction, some toxins to give a few examples
2) Hg is released into the blood, passes into the urine
-Some Hg is processed into hemosiderin which builds in the kidney and then lost in urine as well
What two things do both intra and extravascular hemolysis cause?
1) Increased unconjugated bilirubin
2) Decreased haptoglobin
What is haptoglobin?
A plasma protein that binds free hemoglobin and removes it from circulation; therefore, its levels will fall (it is being used up) when RBCs are being destroyed, as it is in both cases
1) What causes sickle cell anemia?
2) What does sickle cell cause?
1) Single amino acid substitution leading to valine in place of glutamate at 6th amino acid position on the beta hemoglobin
2) HgA (Hg“Adult”) to be turned to HgS (Hg “Sickled”) in homozygotes
(only ½ of the proteins are mutated in heterozygotes)
Sickle cell:
1) What happens to cells w this mutation under hypoxic conditions?
2) What happens during each “episode”?
1) Cells with this mutation undergo sickled structural change, which is irreversible
-Sickled cells hemolyze easily and become stuck in microvasculature
2) Each Each sickle-forming episode leads to influx of calcium which leads to K and H20 loss and damages membrane skeleton
HgA and HgF: By _____________ of age gamma-globin is gradually replaced with beta-globin
six months
1) Explain why sickle cell doesn’t start until 6mo old
2) What specific organ can become enlarged?
3) What do vasooclussive crises in the body cause?
1) In the womb we have HgF (fetal) instead of HgA (adult). HgF persists in the blood stream until 6 months of age onset 6 mo
2) Splenomegaly
3) Pain
Sickle cell symptoms:
1) What is hand-foot syndrome?
2) What is acute chest syndrome?
3) Can sickle cell cause stroke?
4) How can it cause vision loss/ blindness?
1) Infarct in bones in said regions
2) Sluggish blood flow to inflamed lung hypoxia
Stroke
Proliferative retinopathy
4) Vasoocclusions in the eye
Alpha Thalassemia:
1) What is it?
2) What happens once 3 or more alpha-globin chains are lost?
3) What does this lead to?
1) Destruction of 1,2,3, or 4 alleles that code for alpha-globin
2) The cell experiences a vitally low amount of alpha-globin, so the remaining beta-globin pairs into a tetramer
3) Formation of its own tetramer beta-4 in adults, and gamma-4 in infants
Alpha Thalassemia: Infants will build up tetramers of gamma-globin until when?
6 months of age
Both tetramers involved in alpha thalassemia have high affinity for oxygen, so what does this cause?
They won’t let it go
List and describe 2 forms of alpha thalassemia
1) Hb H (4) disease: A moderately severe hemolytic anemia develops because of the gradual precipitation of the Hg H in the erythrocyte.
-This leads to the formation of inclusions in the mature red blood cell, and the removal of these inclusions by the spleen damages the cells, leading to their premature destruction.
2) Hydrops fetalis, Hb Bart’s (4): Infants suffer from severe intrauterine hypoxia and are born with massive generalized fluid accumulation
-This causes infant death
For each Alpha Thalassemia clinical phenotype, list the number of functional alpha genes, the genotype, and the alpha chain production %:
1) Normal
2) Silent carrier
3) Alpha-Thalassemia trait (mild anemia; microcytosis)
1) 4; aa/aa; 100%
2) 3; aa/a-; 75%
3) 2; a-/a- or aa/–; 50%
For each Alpha Thalassemia clinical phenotype, list the number of functional alpha genes, the genotype, and the alpha chain production %:
1) Hb H (B4) disease (moderately severe hemolytic anemia)
2) Hydrops fetalis or homozygous alpha-thalassemia (Hb Bart’s: y4)
1) 1; a-/–; 25%
2) 0; –/–; 0%
Beta Thalassemia:
1) You can either be one of what 2 things for this condition?
2) Decreased beta-globin production leads to what?
3) What does this cause?
1) Heterozygous or homozygous for this disease
2) Imbalance in globin synthesis and the precipitation of the excess alpha chains
3) Alpha chains don’t form their own tetramers; they accumulate in the cell and form a Heinz Body
-This in turn leads to damage of the red cell membrane
-Finally, patients suffer from iron overload due to dietary intake which cannot be accommodated by functional RBCs
G6PD:
1) What is it? What is the mutation?
2) What is G6PD?
3) What is NADPH?
1) Glucose-6-Phosphate Dehydrogenase Deficiency
X-linked recessive mutation in G6PD gene
2) G6PD is an enzyme that processes glucose, which results in production of NADPH
3) NADPH protects red blood cells from the harmful effects of reactive oxygen species
1) G6PD deficiency produces no symptoms until what?
2) What is it a type of and who does it effect?
1) Patients are exposed to environmental factors that increase oxidant stress (e.g., infectious agents, certain drugs and food, severe stress)
2) Hemolytic anemia; 1 in 10 Black males
