RBC abnormalities/Hemoglobin disorders Flashcards
(96 cards)
1
Q
Main function of RBC??
A
transport hemoglobin
2
Q
What are the three classes of Anemia?
A
excessive blood loss
Excessive destruction
Deficient production
3
Q
What are common causes of excessive blood loss?
2
A
Ulcers
GI bleeds
Large intestine= colon cancer-slow
esophageal varices = most rapid blood loss from the GI tract
4
Q
What are common causes of excessive destruction of RBCs?
5
A
spleen(hemolytic anemias)-
sickle cell,
thalassemias,
autoimmune hemolytic anemia, membrane disorders,
5
Q
What are the three common causes of deficient production of RBCS?
A
Deficiency in Iron
B12
Folate
6
Q
What are the three types of morphologic classifications for anemia?
A
- Microcytic hypochromic (iron def- less heme-not as colorful)
- Normocytic normochromic- (anemia of chronic disease)
- Macrocytic normochromic (b12 and folate)
7
Q
What are the three types of etiologic classifications for anemia?
A
Decreased production
Increased loss or destruction
Increased plasma volume (pregnancy)
8
Q
Types of polycythemia?
3
A
- Primary polycythemia (Polycythemia vera-slow growing bone cancer that makes to many RBCs)
- Secondary polycythemia- altitude
- Benign erythrocytosis- regular amount of blood cells but decreased volume
Too many RBCs
9
Q
Someone comes in with signs and symptoms of anemia (SOB and Fatigued). How do we diagnose it?
Why does this help with our diagnosis?
6
A
CBC w/ diff and smear
Tells us:
- number of RBCs
- amount of hemoglobin along
- size
- Smear looks at morphology
- First look at size, then kinetics (microcytic vs. macrocytic with MCV)
- Reticulocyte (precursor of mature RBCs) count….looks at destruction vs. production problem
- reticulocytes are normal or increases then its a destruction problem
10
Q
What stage does hemoglobin synthesis start in RBC growth?
A
early erythroblast stage
-during its transformation from normoblast to reticulocyte
11
Q
What color is a reticulocyte?
A
darker red
12
Q
What color is a normal erythrocyte?
A
yellowish red
13
Q
How long does it take for the stem cell to turn into a reticulocyte?
A
one week
14
Q
Maturation of reticulocyte to erythrocyte takes how long?
How much of the body’s total red blood cells is generated each day?
A
24-48 hrs
1%
15
Q
What is erythropoiesis governed by?
A
tissue oxygen needs
16
Q
What is oxygen content sensed by and what does it do to regulate the changes?
A
Oxygen content is sensed by the kidneys, which produce the hormone erythropoietin
17
Q
How does Erythropoietin act in the bone marrow?
A
by binding to receptors on committed stem cells
18
Q
What are epo’s three functions?
3
A
- Promote hemoglobin synthesis, 2. increases membrane proteins, 3. causes differentiation of erythroblasts.
19
Q
Why is hemoglobin’s binding of carbon dioxide a good thing and also a bad thing?
A
hemoglobin also binds carbon dioxide which is a problem because its similar to carbon monoxide which binds extremely tightly blocking O2.
important that it bonds CO2 so it can get it out of your system
20
Q
When hemoglobin formation is defiecient what will happen to the cells?
2
A
iron deficiency for example.
1. percentage of hemoglobin in the cell may fall considerably and 2. the volume of the cell may decrease
21
Q
When pressure of oxygen is high (as inthe pulmonary capillaries) what does hemoglobin bind?
When pressure of oxygen is low (as in the systemic tissue) what does hemoglobin bind?
A
oxygen and releases CO2
CO2 and releases Oxygen
22
Q
What are all factors that affect hemoglobin function?
3
A
pH, Temp, and CO2 concentration
23
Q
What are some conditions that favor the unloading of oxygen?
A
chronic lung disease/hypoxic pts- COPD
24
Q
TEST QUESTION: Who binds to oxygen?
How many oxygen molcules does each hemoglobin carry?
A
iron, not heme
4
25
What is a hemoglobin chain made of?
What kind of chains does our hemoglobin have?
Heme + polypeptide
2 alpha chains + 2 beta chains => Hemoglobin A molecule
26
What kind of hemoglobin is found in fetuses?
Why do they have this?
When is this replaced?
hemoglobin F which is compased of 2 alpha and 2 gama chains
gamma instead of beta- has to have a higher affinity for oxygen-facilitates oxygen across the placenta
6 months replaced with hemoglobin A
27
Where is most of our iron at?
80%
Where is the other 20%?
Where does iron come from?
complexed to heme in hemoglobin
20% is stored in the bone marrow, liver, spleen, and other organs
get iron from diet (meat, fish, beans and legumes, iron), store it in your cells, body will recycle them
28
What is iron being transported through the blood called?
tranferrin
Transported in the plasma
29
What is iron being stored called?
Where is it stored?
ferritin
liver
30
Describe the breakdown and recycling of iron?
| 3
RBCs are destroyed in the spleen
iroin is released into circulation
and returns to bone marrow
for incorporation into new cells or stored in the liver
31
What happens to the cell as it ages?
Where does this occur?
becomes more and more fragile and can rupture in tight spots in circulation.
In the spleen because the spaces in the red pulp are very small (trabecular network)
32
What happens to the heme unit of the destroyed RBC?
bulk of heme is converted to bilirubin- removed from blood by liver to make it water soluable and excreted in the bile
33
How is the hemoglbin group transported to the right location after the RBC is destroyed?
macrophages of the spleen and bone marrow and kupffer cells of the liver.
These macrophages slowly release iron from the hemoglobin where it is carried by transferrin to the bone marrow or liver
34
What kind of bilirubin causes jaundice?
indirect, unconjugated and insoluable to plasma= jaundice
35
What is Hemolytic Anemia?
premature destruction of red cells
36
Two main types of hemoglobinopathies can cause red blood cell hemolysis. What are they?
1. Abnormal substitution of an amino acid in the hemoglobin molecule, as in sickle cell anemia
2. Defective synthesis of one of the polypeptide chains that form the globin portion of hemoglobin, as in the thalassemias
37
Genetic pathology of sickle cell disease?
Results from point mutation in Beta chain of hemoglobin molecule, with abnormal substitution of a single amino acid, valine, for glutamic acid.
38
How is sickle hemoglobin transmitted?
What are the two ways it can manifest?
recessive inheritance
Sickle cell trait (heterozygote with one HbS gene) or…
Sickle cell disease (homozygote with two HbS genes)
39
Describe the pathophysiology of sickle cell anemia?
At low oxygen tension (really important to remember) HbS becomes sickled
---Sickling occurs as a result of the formation of elongated crystals inside the red blood cells (can be as long as 15 micrometers in length)
40
Sickling causes two major problems. What are they?
1. Makes it almost impossible for the red blood cell to pass through many small capillaries
2. Spiked end of crystals rupture membranes, leading to sickle cell anemia
41
What are the factors that lead to sickling?
5
Anything that may reduce affinity of hemoglobin for oxygen can cause sickling
1. Hypoxia from altitude and infection,
2. cold,
3. stress,
4. physical exertion, or
5. acidosis
42
What can affected sickle cell pts suffer from/how does the disease manifest?
9
Affected patients can suffer from
1. Pain and organ failure due to vessel occlusion
2. Severe hemolytic anemia
3. Chronic hyperbilirubinemia (how might this manifest? jaundice)
4. Acute pain episodes can occur suddenly in almost any part of the body. Common sites include:
Abdomen, chest, bones, and joints
5. Infarction (lack of oxygen to tissue) may cause chronic damage to liver, spleen, heart, kidneys, retina, and other organs
6. Acute chest syndrome: atypical pneumonia resulting from pulmonary infarction
7. Painful bone crises from marrow infarcts of the bones of hands and feet with associated swelling
8. Stroke
9. Spleen damage
43
What is the leading cause of death in sickle cell disease?
acute chest syndrome
44
How do we diagnose and screen for sickle cell disease?
Prenatal diagnosis done by analysis of fetal DNA obtained by amniocentesis
45
How do we manage sickle cell disease?
No cure
1. avoid situations that could cause sickling
2. Reduce symptoms
- pain control
- hydration
3. agressive treatment of infections (Even prohylactic use of penecillin until 5 yrs) and blood transfusion in chronic pts
46
We can treat sickle cell disease with hydroxyurea. What does this do?
Hydroxyurea (a cytotoxic drug) allows synthesis of more Fetal hemoglobin HbF and less HbS, thereby decreasing sickling
47
What is thalassemia caused by?
Cause by absent or defective synthesis of the alpha or the beta chains of adult hemoglobin
48
What does alpha-thalassemia disease cause?
How about beta?
Impaired production of alpha globin chains, which leads to a relative excess of beta globin chains
Impaired production of beta globin chains, which leads to a variable excess of alpha globin chains.
49
How will be heterozygous or homozygous for the disease affect presentation?
hertozygous and have moderate form of the disease
| homozygous is severe form of disease
50
Why does excess of either alpha or beta chain affect the function of the RBC?
imblance of chain production- wont carry oxygen well spleen eats it up
decrease production
51
Another name for beta thalassemia?
Mediterranean anemia
52
Alpha thalassemia is most common among what race?
Asians
53
How does anemia occur in thalassemias?
| 3
1. Reduced hemoglobin synthesis
2. Imbalance in globin chain production leading to deficient hemoglobin synthesis
3. Manifests as hypochromic microcytic anemia (so what would you see with the mean corpuscular hemoglobin concentration [MCHC] and the mean corpuscular volume [MCV]?)
SMALLER and PALE
54
You would see bone aspirations in beta thalassemias. What is a sign of this?
heinz bodies
55
What happens if only one alpha-globin gene is deleted in aplha thalassemia?
What about two?
What about three?
What about all four?
1. Silent carriers have a deletion of a single alpha-globin gene and are asymptomatic
2. Deletion of two genes (Alpha thalassemia trait)? Mild hemolytic anemia
3. Unstable aggregates of Beta chains (lots of em) called Hemoglobin H (HbH) => most persons with HbH have chronic moderate hemolytic anemia and may require transfusions in time of fever or illness or with certain medications
4. Hb Bart’s, which has extremely high oxygen affinity, cannot release oxygen in the tissues. This disorder usually results in death in utero or shortly after birth.
56
Whats the difference in Beta thalassemia heterozygous and homozygous?
1. usually results in sufficient normal hemoglobin synthesis to prevent severe anemia
2. severe, transfusion-dependent anemia that is evident at 6-9 months of age
57
Management of severe homozygous beta thalassemia?
| 3
Management includes frequent transfusions and iron chelation therapy; bone marrow transplantation is a potential cure
58
What is the most prevelent form of thalassemia?
And what is it associated with?
Most prevalent form is Beta thalassemia trait/minor, which is associated with increased hemoglobin A2, increased HbF
59
What is beta thalaseemia major associated with?
persistence of HbF
60
What is alpha thalasseima associated with?
silent carrier state: normal HbA, no clinical manifestations
61
The majority of the time a microcytic anemia will be caused by iron deficiency.
We do not typically order hemoglobin electrophoresis when working up a microcytic anemia, therefore, specific lab tests that help you to suspect a thalassemia
are what?
3
normal RDW,
a decreased RBC count, and
a normal Ferritin (best marker for iron)
62
The combination of a normal RDW and a low MCV has what type of specificity and sensitivity for detecting thalassemia?
high specificity
| low sensitivity
63
A low MCV and an elevated RDW is more suggestive of what?
iron deficiency anemia
64
What does gene G6PD do?
What would an inherited enzyme defect of G6PD cause?
protects red blood cells
make red blood cells vulnerable to oxidants and causes them to denature forming Heinz Bodies
65
What medications should we avoid if we have G6PD deficiency?
| 6
1. Primaquine,
2. the sulfonamides,
3. Nitrofurantoin,
4. aspirin,
5. phenacetin and some
6. chemotherapeutics can cause hemolysis
66
How would we diagnose inherited G6PD enzymes defect?
G6PD assay
67
What is G6PD defiency characterized by?2
epidsodic anemia, G6PD deficiency, predominantly in males
68
What does CO form when it binds to hemoglobin?
carboxyhemoglobin (COHb)
69
What are the signs of carbon monoxide poisoning?
sleepy fatigue headache hazy
horrible headache in morning- gets better during the day
CNS toxicities, most of the symtppoms will present this way
70
Where is lead stored and eliminated?
stored in bone and eliminated by the kidneys
71
the half life of lead is hours to days so how does small amounts accumulated over time lead to toxicity?
bone deposits serve as a repository, or “sink,” from which blood levels are maintained
In a sense, bone protects other tissues, but the slow turnover maintains blood lead levels for months or years
72
A deficiency of what will lead to an absorption of lead?
| 3
deficiency in calcium iron or zinc
73
What does lead toxicity do to the body?
| 3
1. Inactivates enzymes
2. Competes with calcium for incorporation into the bone
3. Interferes with nerve transmission and brain development
74
What are the 4 major targets of lead toxicity?
RBCs- check CBC
GI tract
Kidneys
Nervous system- long term problems
75
What is the cardinal sign of lead toxicity?
anemia
| -competes with enzymes required for hemoglobin synthesis
76
The resulting RBCS in lead toxicity are described as what?
MICROCYTIC and HYPOCHROMIC (similar to iron deficiency anemia)
Decreased life expectancy too
77
What is the hallmark sign of lead toxicity?
basophilic stippling!
78
Where is the main source of symptoms in lead toxicity and what does it present as?
GI tract is the main source of symptoms
“Lead colic”
A severe and poorly localized form of acute abdominal pain
79
What in the bones is a symptoms of lead poisoning?
Seen in two places in the body
2
Lead line”
May be seen at the
1. metaphysis in the long bones of growing children…caused by disrupted calcium metabolism
Formed by precipitated lead sulfite may appear along the
2. gingival margins…more often seen in adults
80
Why is the kidney affected and what is an early sign of kidney failure due to lead toxicity?
Major route of excretion
Lead exposure can lead to renal failure
Hypertension may be an early sign
81
Nervous system symptoms due to lead poisoning are characterized by what?
demyelination of cerebral and cerebellar white matter and death of cortical cells
82
How can these neuro symptoms of lead poisining affect children?
Lower IQ
| Poor classroom performance
83
Whats the most serious symptom of lead poisening?
Signs of this symptom occuring?
6
Acute encephalopathymay present suddenly, or be preceded by behavioral changes or abdominal complaints
```
Persistent vomiting
Ataxia
Seizures
Papilledema
Impaired consciousness
Coma
```
84
What is a high lead level?
5ug/dL
85
How does lead cause elevated levels of free erythrocyte protoporphyrin (EP)?
result from the inhibition by lead of the enzymes required for heme synthesis in RBCs
86
How would we treat lead poisoning?
| 3
1st: Remove the lead source!
2nd: Chelating agents (bind and excrete)-for severe toxicity
3rd: Asymptomatic children with blood lead levels of 45-69 ug/dL usually are treated
- D-penicillamine
- Succimer
- Dimercaprol
- Edetate disodium calcium
87
How does acidosis cause anemia?
reduces the affinity of hemoglobin for oxygen
88
What laboratory tests woudl we do for acidosis?
| 6
1. RBC count: total number
2. % of Reticulocytes: rate of production
3. Hemoglobin: grams of HgB per 100 mL of blood
4. Hematocrit: volume of red cell mass in 100 mL of plasma volume
5. MCV: volume or size
6. MCHC: concentration of hemoglobin in each cell (color)
89
What is normochromic anemia?
What kind of anemias does this encompass?
4
Concentration of hemoglobin in the cell is in the normal range
However, there are not enough red blood cells
1. aplastic,
2. post-hemorrhagic,
3. hemolytic anemias, and
4. anemia of chronic disease
90
What is the most frequent type of anemia?
Normocytic Anemia
91
What is Normocytic Anemia?
What does the pathology of this lead to?
5
MCV is in normal range
Hematocrit and Hemoglobin are decreased
```
Decreased production of rbcs
Increased production of HgS
Increased destruction
Increase in plasma volume
B2 and B6 deficiency
```
92
What is hypochromic anemia?
What kind of anemias are associated with this?
2
1. Red blood cells are pale
- -Increased central pallor
- -HgB is what adds the red pigment
- -Red Blood Cells are also usually small
Fe deficient Anemia and Thallasemia
93
What is Microcytic Anemia?
What kind of anemias are associated with this?
Small Red Blood Cells
MCV Decreased
Also, MCHC, because usually goes with hypochromic
Fe deficiency and Thallasemia
94
What is macrocytic anemia?
What kind of anemias is this seen in?3
Red Blood Cells are large
Hemoglobin also down
Folate, B12, Codocytes (target cells)
95
What is anisocytosis?
And what kind of anemia is this seen in?
RBCs are of unequal size
RDW - high
FE DEFICIENCY ANEMIA AND THALLASEMIA
96
What is Poikilocytosis?
What kind of anemia is this seen in?
2
Abnormal shaped RBCs
Flattened disks that are thinner in the middle than at the edges
Abnormal if make up >10%
Membrane abnormalities and trauma
