Lecture 5.1 Highlights Flashcards
What is one lab you should always measure the change of?
Hemoglobin
What leads to the release of unconjugated bilirubin? Why?
1) RBC lysing
2) The bili wasn’t able to be conjugated through normal delivery to the liver
Hemolysis leads to an increase in what? What should you check?
Check the reticulocyte count; it will be high in chronic blood loss
Intravascular and extravascular hemolysis both can cause increased ________________ and decreased __________
unconjugated bilirubin; haptoglobin
Hereditary Spherocytosis:
1) What part of the RBC is defective?
2) What does this do to the cell?
1) Membrane
2) Spherical, non-deformable
Hereditary Spherocytosis:
1) Is caused by mutations in either one of two proteins; what are they?
2) What do these mutations do?
3) What happens to affected RBCs?
1) Ankyrin or spectrin
2) Cytoplasm released until surface to volume ratio is decreased forming a sphere
3) Destroyed by macrophages in the spleen
How is hereditary spherocytosis (which causes extravascular hemolysis) treated?
Splenectomy
Sickle cell is caused by a single amino acid substitution leading to valine in place of glutamate at 6th amino acid position on the _____________
beta hemoglobin
Sickle cell causes Hg____ to be turned into Hg____
HgA; HgS
Sickle cell: Under _________ conditions, cells with this mutation undergo _____________ change, which is irreversible
hypoxic; sickled structural change
Sickle cell: Each sickle-forming episode leads to influx of calcium which leads to K and H20 loss and damages ____________
membrane skeleton
Sickled cells _____________ easily and become stuck in ______________
hemolyze; microvasculature
HgA and HgF: By _____________ of age gamma-globin is gradually replaced with beta-globin
six months
HgF is a combination of ______________ and alpha-globin
gamma-globin
When is the onset of sickle cell Sx?
6 months old
Sickle Cell vasoocclusive crises in body are characterized by what?
Pain
Thalassemias are disorders associated with what?
Imbalance in production of alpha or beta globin
Thalassemias causes the formation of hemoglobin molecules that have what?
An abnormal number of alpha or beta globins
Why are Thalassemias a problem?
The alternate hemoglobins do not bind oxygen efficiently and can be lethal
What is the most common cause of alpha thalassemia?
Deletion(s) of one or both alpha globin genes
There are _____ different genes for alpha globin, and thus _____ alleles
two; 4
1) What is the most common cause of beta thalassemia?
2) How many genes and alleles are involved?
1) Single-base pair substitutions that result in proteins that have either reduced activity, altered activity, or no activity at all
2) One gene with two alleles
Beta Thalassemia:
Decreased ______________ production leads to in imbalance in globin synthesis and the precipitation of _______________.
beta-globin; excess chains
Alpha chains don’t form their own tetramers; what do they do instead?
Accumulate in the cell and form a Heinz Body
Beta thalassemia: patients suffer from _______________ due to dietary intake which cannot be accommodated by functional RBCs
iron overload
1) Carriers of one beta-thalassemia allele are clinically well, and have what condition?
2) Who would have a different version of this condition?
1) Thalassemia minor
2) In regions of the world where beta-thalassemia is common (malaria belt) individuals may be homozygous recessive or compound heterozygotes for two different beta-thalassemia alleles and have thalassemia major
What is a condition characterized by severe anemia and the need for lifelong medical management?
Beta thalassemia
Beta thalassemia major: Prominent cheekbones and protrusion of upper jaw result from ______________________ in bones of skull and face
expansion of marrow cavity
G6PD produces no symptoms until patients are exposed to environmental factors that increase what? Give examples
Oxidant stress (e.g., infectious agents, certain drugs and food, severe stress)
1) What type of anemia is G6PD?
2) Who does it affect?
1) Hemolytic anemia
2) 1 in 10 Black males
Peripheral blood smear shows RBC with precipitates of denatured globin, aka what?
Heinz bodies/ bite cells
List 4 diagnostic criteria for iron deficiency anemia
1) Transferrin saturation low
2) Total iron-binding capacity HIGH
3) Ferritin low
4) Microcytic red cells
Anemia of Chronic Disease:
1) Inflammatory _________ increases hepatic _________
2) What does this block?
3) What else is occurring?
4) Will ferritin be high or low?
1) cytokines; hepcidin
2) Hepcidin blocks iron from being added to RBCs
3) Chronic inflammation blunts EPO synthesis
4) High
There’s a high risk for folate deficiency in what two groups?
Poor nutrition and pregnant women
B12 anemia is accompanied by __________ symptoms
neurologic
B12 deficiency (megaloblastic): The anemia may be improved with the administration of folate, but what won’t?
Neurological symptoms will not, and may even worsen
Aplastic Anemia:
1) What causes it?
2) What are half the cases?
3) What makes up the other half?
4) What are 3 Sx that can be seen in labs?
1) Suppression of multipotent myeloid stem cells
2) Idiopathic
3) Exposure [to myelotoxic agents]
4) Anemia, thrombocytopenia, neutropenia
Alpha thalassemia:
1) Once _______________ alpha-globin chains are lost, the cell experiences a vitally low amount of alpha-globin, so the remaining beta-globin pairs into a tetramer
2) This leads to formation of what in adults and what in infants?
1) Three or more
2) Its own tetramer beta-4 in adults, and gamma-4 in infants
Alpha thalassemia: What do tetramer beta-4 and gamma-4 have in common?
Both have high affinity for oxygen, so they won’t let it go
Give 2 examples of Alpha Thalassemia
1) Hb H (Beta 4) disease
2) Hydrops fetalis, Hb Bart’s (y4)
True or false: Alpha chains don’t form their own tetramers
True; they accumulate in the cell and form a Heinz Body
Beta Thalassemia pts suffer from ____________ overload due to dietary intake which cannot be accommodated by functional RBCs
iron
Anemia of Chronic Disease
1) Iron is actually being _________ so ferritin is high
2) Therefore, iron is not _________ so TIBC is low
3) The MCV remains _________ and the cells are not hypochromic
1) stored
2) desired
3) normal
1) What is bone marrow failure and pancytopenia caused by in aplastic anemia?
2) What are the two main causes?
1) Suppression of multipotent myeloid stem cells
2) Idiopathic + exposure
List 3 Sx of aplastic anemia
Anemia, thrombocytopenia, neutropenia
Define polycythemia
Polycythemia (erythrocytosis): the result of an abnormal increase in red blood cell number
Clonal proliferation of myeloid stem cells causes what?
Primary polycythemia (polycythemia vera)
1) What hormone is involved with secondary polycythemia’s erythroid bone marrow hyperplasia?
2) What is usually the cause?
3) Give examples of causes
1) Erythropoietin
2) Prolonged hypoxia
3) Living at high altitudes, anoxia secondary to chronic lung disease, congenital heart disease, renal carcinoma
List 4 Sx of polycythemia vera
1) Hypertension
2) Dark red or flushed face
3) Headaches
4) Pruritis
What is a risk of polycythemia vera?
Increased risk of deep vein thrombosis (DVT),
Name something that causes lymphadenitis with the etiology of Bartonella hensale
Cat-Scratch Disease (most common in axilla and neck)
What happens in leukemia?
Bone marrow is infiltrated with malignant cells
Bleeding disorders:
1) TTP is caused by what?
2) What causes Hemolytic uremic syndrome?
1) Acquired or inherited deficiencies of ADAMTS 13
2) Deficiencies of complement regulatory proteins
