1
Q
What makes up hemoglobin?
A
- Hemoglobin is found in lab value by spinning down blood and separating from plastma. Formed elementts (45% RBC) also includes buffy coat is made up of WBC, PLT
- Hemoglobin is composed of :
- heme- iron and porphyrin ring
- globin- 2 alpha, 2 beta globins to make tetrameric hemoglobin
2
Q
What are reticulocytes?
A
- “baby” RBC, look like RBC but it still has RNA/ribosomes and are still making Hgb
- not quite mature or finished making hgb
- useful for differential diagnosis of various anemias
- Circulate for 1 day (under normal conditions)
- 1% blood are reticulocytes (under normal conditions)
3
Q
What are erythrocytes
A
- Mature RBC. No more hemoglobin synthesis
- Circulate for 100 days and recycled via the spleen
4
Q
How does the spleen recycle RBC?
A
- Mostly get recycled in the spleen
- RBC comes in one end, has to go through sinusoidal capillary in order to get into red pulp. At other side of red pulp, squeezes through endothelial gap
- squeezes through endothelial cap to get into sinusoidal capillary(unclear on this exact mechanism, can’t find extra resources). BUT If RBC can’t make it through the gap( rbc is too old/stiff) and stays in red pulp, macrophage in the “red pulp” in the spleen will eat the RBC
- this is how we clear most of RBC (in spleen)
- quicker RBC can get out of pulp and into sinusoid will survive. old ones will get eaten
- Macrophages can also pluck out pieces of the RBC without destorying the whole thing
5
Q
What is the trigger for making more RBC?
A
erythropoietin
- Uncommitted pluripotential stem cell + erythropoietin–> commited proerythroblast (committed to eventually become RBC)
6
Q
What is hypoxia? Hypoxemia?
A
- Hypoxia is reduced tissue oxygenation
- Hypoxemia is reduced partial pressure of oxygen in the blood
7
Q
What does anemia result in, in relation to hypoxia and hypoxemia?
A
anemia results in hypoxia without hypoxemia
8
Q
What is hypoxemia without hypoxia
A
polycythemia
9
Q
What are some manifestations of anemia?
A
More or less what garman said about picture:
- Weakness/fatigue
- pallor
- increased RR, depth
Compensatory mechanisms from tissue hypoxia
- pump more blood (CV)
- increase SV
- Increase HR
- Capillary dilation
- kidney increases blood volume
- further increases CO
- little anemia is fine
- problem if very anemic, will get HUGE increase CO and then you run into high output cardiac failure (blood moving so fast that it doesn’t have time to unload oxygen at tissues)
- also get heart murmurs with High output cardiac failure
- this is seen at HCT in 20s
- further increase in CO won’t help because of decreased time in capillaries
- we need to make more RBC to fix the problem!! (kidney will kick in with more erythropoitin and signal body to make RBC)
10
Q
What does tissue hypoxia in anemia cause?
A
- Ischemia
- claudication (muscle)
- weakeness, increase fatigue
- pallor (skin /mucous membrane)
- Respriatory: increase RR, depth, “exertional dyspnea”
- CNS - dizziness, faiting, lethargy
- Liver
- fatty changes. fatty changes also occur in heart and kidney
11
Q
What are some compensatory mechanisms from anemia?
A
- Increase oxygen demands for work of heart
- heart (angina)
- increase erythropoietin
- stimulated bone marrow
- CV changes
- increase HR
- Capillary dilation
- increase SV
- Hyperdynamic ciruclation
- cardiac murmurs
- high-output cardiac failure
- Hyperdynamic ciruclation
- renal (he said this should be by increase erythropoietin)
- increase Renin-aldosterone response
- increase salt and h2o retention
- increase ECF (furhter causing hyperdynamic circualtion)
- Increase DPG in cells
- increase release of oxygen from hemoglobin in tissues
12
Q
Will increasing CO in a severely anemic patient help with hypoxia?
A
No, need more RBC!
Blood already doesn’t have enough time to unload o2, so increasing CO does not help the situation
13
Q
What is physio process behind stimulating RBC production?
A
Role of erythropoietin in regulation of erythropoiesis. Decreased arterial oxygen levels stimulate production of erythropoietin, which in turn stimulates red cell production and expansion of the erythron. The increase in red cells frequently corrects the problem of low oxygen levels (hypoxia). The restoration to normal oxygen level alerts the kidney to stop producing erythropoietin
14
Q
What are 4 main categories of anemia?
A
- Macrocytic
- Microcytic
- Normocytic-normochromic from decreased erythrocyte production
- Normocytic-normochromic from increased erythrocyte turnover
15
Q
What is macrocytic anemia? Causes?
A
- MCV >100 fL (megaloblastic anemia)
- problem with DNA syntehiss
- DNA syntehsis is slow d/t decreased amt of nucleotides but cell continues growing while it’s waiting on DNA to replicate
ex:
- B12 deficiency- lack of IF degrades the B12 before it can be absorbed in the GI tract
- Folate Deficiency- common in alcoholics, processing alcohol depeltes folate
- Any drug (ie chemo drugs) that inhibit DNA synthesis
16
Q
What is microcytic anemia? Causes?
A
- MCV <80 fL
- problem with hemoglobin synthesis
- results in a small, pale cell (hypochromic)
Causes:
- Iron deficiency- usually results from blood loss (adults) or nutritional deficiency (children)
- Thalassemia- genetic defect in alpha globin or beta globin
- therefore can’t make the tetrameric heme we need ofr hemoglobin
17
Q
What is normocytic-normochromic anemai caused by decreased in erythrocyte production? RI? Causes?
A
Normal size RBC, normal color. Just not making enough RBC. Low RI
Causes:
- Anemia of chronic renal disease (EPO deficiency)
- anemia of chronic disease- attempt to keep iron away from bugs (also microcytic)
- Sideroblastic anemia- defect in iron handling–> dysfunctional hemoglobin (also microcytic). Can’t put iron in porphyrin ring
- genetic
- acquired- lead poisoning
- Myelofibrosis- marrow replaced with fibrosis (w/pancytopenia)
- Aplastic anemia- marrow repalced with fat
- gneetic- congenital aplastic anemia (fanconi anemia)
- Acquired- due to bone marrow toxicity, typically from drugs
18
Q
What causes anemia of chronic disease?
A
- Heme is important in many enzymes (anyone that processees oxygen)
- Bacteria also need iron for much of the same reason (enzymatic processes)
- during anemia of chronic disease, our immune system (macrophages) keep iron away from bacteria
- keep iron locked away in macrophages
- looks iron deficient but different
- iron defiicent= give iron and fix
- anemia of chronic disease- iron does NOT fix problem
- occurs in infectious and chronic dx
normocytic-normochromic anemia d/e decreased erythroyte produciton (low RI)
19
Q
What is sideroblastic anemia?
A
Defect in iron handling–> dysfuncitonal hemoglobin ( also microcytic)
- have iron, have porphyrin ring, but can’t put iron in porphyrin ring
- genetic
- acquired- lead poisoning
- lead looks like iron, enzyme picks up lead
- lead binds irreversibly
- now enzyme that puts iron in porphyrin, is blocked by the lead
normocytic-normochromic anemia d/e decreased erythroyte produciton (low RI)
20
Q
What is myelofibrosis?
A
- marrow replaced with fibrosis (seen w/ pancytopenia- loosing bone marrow)
- normocytic-normochromic anemia d/e decreased erythroyte produciton (low RI)
21
Q
What is aplastic anemia
A
- marrow repalced with fat (w/pancytopenia)
- genetic- congenital aplastic anemia (fanconi anemia)
- acquired- due to bone marrow toxicity, typically from drugs
normocytic-normochromic anemia d/e decreased erythroyte produciton (low RI)
22
Q
What are causes of normocytic-normochromic anemia from increased erythrocyte turnover? RI?
A
- Normal cell size, nomal color. HIGH RI
Causes:
- Hemolytic anemia
- membrane defect
- metabolic defect
- hemoglobin defect
- hemolytic disease of the newborn
- hemorrhagic anemia
23
Q
What is reticulocyte index?
A
- Reticulocyte count corrected for degree of anemia
- the more anemic someone it, the more we expect them to make RBC
- Under normal conditions, reticulocytes exist for 1 day, BUT if someone is anemic, the reticulocytes will be released earlier and they’ll circulate longer as reticulocytes
- no anemia- RI should be 0.5-2%
- anemia- RI should be >2%
- Equation (unsure if we actually need to know)
- RI= [(reticulocyte count * HCT)/ normal HCT (45%)]/ day as reticulocyte
24
Q
HCT % and days spent as reticulocyte?
A
- 36-45= 1 day as reticulocyte
- 26-35= 1.5 days as reticulocyte
- 16-25= 2 days as reticulocyte
- <15= 2.5 days as reticulocyte
25
What values do we look at to determine iron levels in blood?
* Most of free iron stored in liver,
* look at 4 things
* **serum iron**
* **transferrin**- molecule that is used ot carry o2 from one place in body to another
* never want iron to be free, we want it bound to protein!
* free iron dangerous and can produce ROS or bacteria can pick it up
* **transferin saturation**- amount of iron moving to bone marrow
* **ferritin**- amount of iron stored inside cells
* some ferritin will leak out of cells into blood
* this ferritin is good indicator of iron status
26
What does serum iron and total iron binding capacity look like in iron deficiency
* Serum iron- low
* transferrin- high
* trying to move what iron you do have around
* *from kahn acadeomy- compensatory mechanism to increase transferrin when serum iron low. (but this is NOT the case in anemia of chronic dx\_*
* transferrin saturation -low
* have so little iron, that the transferrin isn't getting filled up with iron
* ferritin- low
* (stores inside cell)
* no extra iron, so no iron stores inside cells
27
What does serum iron and total iron binding capcity look like in anemia of chronic disease?
* Serum iron- low
* because we are anemic and don't have enough RBC
* transferrin- low
* *from kahn academy video- anemia of chronic dx stops the normal response of increasing transferrin (part of the protective mechanism to keep iron away from bugs), so therefore transferrin is low.*
* transferrin saturation- normal
* the transferrin that is present, has lots of iron
* ferritin- normal/high
* high concentraiton of iron inside cells (keeping it away from bacteria)
28
What causes right shift of hemoglobin dissociation curve?
right shift causes reduced affinity for o2
* increased temperature
* increased 2,3- DPG
* Increase H
^^ on slide
from before "cadet faces right"
C- hypercarbia
A- acidosis
D- 2.3 DPG
E- Exercise
T-temperature
29
What causes left shift on oxyhemoglobin dissociation curve
Left= love= hold onto O2
* Decreased temperature
* decreased 2,3, DPG
* Decreased H
* CO (carbon monoxide)
30
How do we compensate for altitude changes quickly?
Increase 2,3 DPG to encourage offloading of O2 form hgb (right shift, release O2)
31
What are some other hemoglobin-related d/o?
* **Hemoglobins with increased oxygen affinity (right shift)**
* **Hemoglobin with decreased oxygen affinity (left shift)**
* **Methemoglobinemia******
* Methemoglobin has lower affin for O2, but increases the affin of O2 for the other 3 hemes, resulting in greatly decreased O2 delivery
* You lose one O2, the other irons are not going to give up theirs
* **polycytemia (erythrocytosis)**
* **polycythemia vera (stem cell disorder)→ make too many RBC**
* Vera=true. Nothing caused it, it just happened
* Can have hct ~ 48%, athletes.
* Up to 75%- prob → viscosity of blood high (heart has hard time pumping, can lead to HF \*)
* **secondary polycythemia due to hypoxia- secondary to cardiac or pulmonary problem**
* Ex: COPD -high Hct to comp for low oxygenation
* can have hypoxemia w/o hypoxia bc have such high Hct
* **secondary polycythemia due to increased epo-** *kidney producign too much epo)*
32
What is macrocytic anemia?
* Trouble making DNA, b/c of DNA synthesis, but don’t have trouble making cell, so the cell gets larger and larger while wait for DNA replicationà large RBC cell
* B12 deficiency and folate deficiency both impair DNA synthesis and produce macrocytic anemia.
* _NOTE_: B12 deficiency can also produce neurological symptoms, while folate deficiency does not.
* Also caused by drugs that impair DNA synthesis.
**Causes**: ↓IF ® B12 deficiency ® impaired DNA synthesis
* decreased¯IF due to autoimmune destruction of parietal cells
* Gastric parietal cells secrete IF
* deficiency may be genetic or acquired
* Deficiency may be genetic or acquired
* Loss of IF, can be genetic or acquired, decrease in IF, decreases B12 b/c need IF to protect B12 through digestive tract
* Can absorb B12 sublingually or take B12 injection
* Easy to treat, one injection per year probably
* We don’t use much B12, have a lot of it stored
* If have lack of IF or lack of B12 in body, and wait long enough will cause impaired DNA synthesis
* **Alcoholism**, resulting in folate depletion, is the **most common** cause of macrocytic anemia.
* Give folate or have person stop being an alcoholic
* Chemo can cause this, this is expcted
In general, having trouble making RBC bc have a hard time replicating DNA
* Neutropenia will also occur
33
What is hypochromic microcytic anemia of iron deficiency?
* pale and small cells from lack of iron
* (pic from lecture had microcytic cells mixed with normal RBC- a blood trasnfusion caused this)
* want to determine cause of iron deficiency
* 20 yo- likely mensturation
* 40yo postmenopausal- can be cancer, other issues, don't just dismiss
34
How do we recycle iron?
* spleen digest RBC
* heme- iron and porphyrin
* recycle iron from heme- more valuable than gold
* porphyrin ring- waste and becomes bilirubin
* globin
* AA of globin also recycled
* When we breakdown the RBC, we won't ever lose iron
* in hemolytic anemias- don't ever lose iron
* If bleeding from GI ulcer, then iron is lost
* iron absorbtion in GI tract is very very low and will ultimately result in iron deficient anemia
Text from picture:
* Iron (Fe) released from GI epithelial cells circulates in bloodstream assoc w/ its plasma carrier, transferring. It’s delivered to erythroblasts in bone marrow, where most of it’s incorporated into Hgb.
* Mature erythrocytes circulate for ~100-120 days, after they become senescent and are removed by the mononuclear phagocyte system (MPS).
* **Macrophages of MPS (mostly in spleen) break down ingested erythrocytes** and return iron to bloodstream directly or after storing it as a ferritin or hemosiderin
35
What is aplastic anemia?
* Top- white speckles= fat, red= bone marrow
* lower= lots of fat and little islands of bone marrow left over
* red marrow is converted to yellow marrow and losing capacity to make RBC
* leads to pancytopenia- deficiency in all blood cells
* Anemia first to show because most obvious
* neturopenia will be big problem and lead to infections
36
What is myelofibrosis?
* Scar tissue starts to replace bone marrow
* this squeezes RBCs being developed
* causes tear drop shape of RBC (Tell-tale sign of myelofibrosis)
* order bone marrow bx to look at bone marrow
* fibrosis of bone marrow--\> pancytopenia with poikilocytosis (misshapen cells)--\> extramedullary hematopoiesis--\> hepatosplenomegaly
* extramedullary hematopoiesis= because bone marorw so damaged, hematopoiesis moves BACK to liver/spleen (where it first occured in utero)
* this causes your liver/spleen to enlarge
Myelofibrosis with myeloid metaplasia (peripheral blood smear).
Two nucleated erythroid precursors and several teardrop-shaped red cells (dacryocytes) are evident. Immature myeloid cells were present in other fields. An identical picture can be seen in other diseases producing marrow distortion and fibrosis.
37
What are some hemolytic anemias caused by a membrane defect?
* Hereditary spherocytosis
* herditary elliptocytosis
* acanthocytosis
* paroxysmal nocturnal hemoglobinuria (not genetic)
first 3 are genetic
38
Hemolytic anemais caused by metabolic defect?
* Glucoe 6 phosphate dehydrogenase deficiency
* glutathrione reductase deficiency
* pyruvate kinase deficiency
* methemoglobin reductase pathway (causes left shift)
* luebering-rapoport pathway (causes left shift)
39
Hemolytic anemia caused by hemoglobin defect?
* Sickle S hemoglobin- classic sickle cell anemia
* Sickle C Hgb- looks like sickle cell but diff mutation
* sickle hemoglobin B thalassemia (combined HbS (sickle cell) with thallassemia)
40
What is hereditary spherocytosis?
* lose central pallor in RBC
* type of membrane defect that causes hemolytic anemia
* defect in cytoskeleton anchor (aka proteins spectrin and ankyrin) to the plasma membrane
* end up with little blebs. as these blebs leave the cell, we lose more SA compared to volume.
* SA/volume ratio changes (SA goes down more than volume)
* need to change RBC to be **optimal package** which is a sphere
* now can't get through spleen
* splenic macrophages clear RBC at higher rate (shortened ciruclation half-life)
* all these anemias help to decrease r/f malaria, because if you turn over RBC faster, less likely to be infected by malaria
* **autosomal dominant pattern**
* most common inherited hemolytic anemia in europ and US (1:5000)
* can end up with hemolytic crisis, often precipitated by viral or bacterial infection
On smear:
* anisocytosis (unequal sized RBC) and several dark appearing spherocytes with no central pallor
* howell-jolly bodies (small dark nuclear remanants) also present
41
What is elliptocytosis?
Membrane defect in RBC that causes hemolytic anemia
* abnormality in onf ot eh membrane proteins, spectrin or glycophorin
* inherited as an autosomal dominant disorder
* prevalent in regions where malaria is endemic
* *similar problem to spherocytosis, but diff defecta nd changes chape in diff way*
* *decrease lifespan RBC, turnover faster, malaria less risk, clear faster*
* *not terribly bad anemia c/t sickle cell*
42
What is acanthocytosis?
Type of membrane defect (genetic) that causes hemolytic anemia
* defect in membrane structure found in patients with a congenital lack of B lipoprotein
* results from cholesterol or sphingomyelin accumulation on outer membrane of erythrocytes
* gives membranes a spciualted appearance and signals the splenic macrophages
* mode of inheritiance is autosomal recessive
* *defect in cholesterol B lipoproteins*
* *defect in lipid bilayer that causes spike*
* *easy for pslenic macrophage to find/destory*
43
Paroxymal nocturnal hemoglobinuria?
Membrane defect that results in hemolytic anemia. Only cause that isn't genetic, acquired via mutation
* Cuases RBC to attrat immune system
* Patient pass dark colored urine in morning owing to the presence of hemosiderin in blood (hemosiderin is water soluble and cleared by kidneys, is black)
* completement activated RBC hemolysis
* patients are at risk for other complications of Hb release
* smooth muscle dystonia, pulm htn, renal insufficiency, hypercoagulability
* thomboses occur in approximately 40% of patients
* about 1/3 develop aplastic anemia
* Nocturnal manifestations of hemolysis is thought to result from CO2 retnetion and subsequent repsiraotyr acidosis
* *why it tends ot occur at night when people aren't breathing enough (especially apnea)*
44
What is gutathione reductase defieicency?
* Crucial part of antioxidant pathway
* if we lose glutathione, lose cpacity to clear antioxidants
* more damage occurs and increase RBC clearance
45
What is glucose-6-phosphate dehydrogenase deficiency? What can be seen on blood smear in G6PD def?
* Loss of G6PD pathway, so protein with damage will accumulate
* heinz bodies will occur
* useful to help with malaria
* X-linked, mostly affects males
* 400 million people worldwidde
* 10% african american men in USA
* \>10% of men worldwide
* fava beans trigger RBC breakdown
Peripheral blood smear from pt with glucose-6-phosphate dehydrogenase deficiency after exposure to an oxidant drugs
* red cells with precipitates of denatured globin (heinz bodies= inclusions)
* as splenic macrophages pluck out these inclusions "bite cells" like the one in the smear are produced
46
What is methemoglobin reductase pathway
* methemoglobin- occurs naturally but we don't wnt it because it causes left shift of oxyhemoglobin
* with this pathway, can remove methyl group on hemoglobin
* if we lose this pathway, methemoglobin will accumulate
47
What is luebering-rapoport pathway?
* Lose ability to amke 2,3 DPG, causes left shift
48
What is sickle cell anemia?
* Sickle cell hemoglobin is produced by a recessive allele of the gene encoding the beta chain of the protein hemoglobin
* it represents a single amino acid change- from glutamic acid to valine at the sixth position on the chain
* sickle cell shape will prevent blood from going through capillary
* this will cause hypoxemia/ishcemia thorugh capillary
* the base pair change causes spikes to stick our of RBC
* now RBC can "stack" on top of each toher, getting caught in capillaries
49
What causes the sickling of erthrocytes in sickle cell anemia?
* Need 2 bad HbS genes before affected
* if Only one HbS gene bad, you will be a carrier
* Some sort of insult - hypoxemia, decreased pH, low temperature, and/or decreased plasma volume occurs causing RBC to sickle
* resume normal shape when reoxygenated by lungs
* sometimes will get "stuck" in sickle shape, start to get stuck on eachother, causing sick cell crisis
* like "feeling the burn" with exercise but won't go away and is very painful
* Treatment- O2, volume pain killers
50
What are clinical manifesattions of sickle cell disease?
* Every organ in body can be affected by sickle cell disease
* some will be particularly hartd hit (autosplenectomy) shrinks into nothing
51
What is B-thalassemia?
* problem with beta globin
* make insufficient or defective beta globin
* when alpha and betas paired, not enough betas and some alphas are left over
* these alphas stick to eachother and end up with aggregates of alpha globin
* aggregate is prime target for the spleen and spleen clears the cells
* since we're turning over cells and have anemia, will trigger increase iron absorption from GI tract
* we don't have iron deficiency, we have turnover problem
* will start to use other bone marrow to make RBC (skull)
52
Can we treat thalassemia by giving blood transfusion?
No, don't have iron deficiency. will lead to iron overload
53
Thalassemia, HbS, HbC, Pk deficiency play a role in decreasing \_\_\_\_
malaria
54
A thalassemia more common in \_\_\_
b thalassemai more common in \_\_\_
asia; meditarranean
55
What is hemolytic disease of the newborn?
* Fetus rH + and mom rH -
* at birth (first baby), some mixing of maternal and fetal blood
* maternal immune system sees rH factor and makes memory cells against it
* 2nd fetus, enough blood leaks through placenta and triggers response from memory cells
* produce anti rH antibodies (igG in nature) that can cross placenta and go to fetus
* Maternal antibodies in fetus then attack fetal blood
* fetus born with low RBC count and lots of bilirubin d/t digested rbc
* immature fetus liver cannot handle the incresed bilirubin
* baby needs bili light and will improve
Hemolytic disease of the newborn (HDN).
A, Before or during delivery, Rh-positive erythrocytes from the fetus enter the blood of an Rh-negative woman through a tear in the placenta.
B, The mother is sensitized to the Rh antigen and produces Rh antibodies. Because this usually happens after delivery, there is no effect on the fetus in the first pregnancy.
C, During a subsequent pregnancy with an Rh-positive fetus, Rh-positive erythrocytes cross the placenta, enter the maternal circulation, and stimulate the mother to produce antibodies against the Rh antigen. The Rh antibodies from the mother cross the placenta, using agglutination and hemolysis of fetal erythrocytes, and HDN develops. (Modified from Seeley RR, Stephens TD, Tate P: Anatomy & physiology, ed 3, St Louis, 1995, Mosby.)
56
Name d/o associated with cell.
Don't worry about D, H, I
Appearance of red blood cells in various disorders.
A, Normal blood smear.
B, Hypochromic-microcytic anemia (iron deficiency).
C, Macrocytic anemia (pernicious anemia).
D, Macrocytic anemia in pregnancy. \<**don't worry about this one**
E, Hereditary elliptocytosis.
F, Myelofibrosis (teardrop).
G, Hemolytic anemia associated with prosthetic heart valve.- valves dmage RBC and have pieces leftover
H, Microangiopathic anemia.**\<\< don't worry**
I, Stomatocytes.**\<\< didn't talk about**
J, Spherocytes (hereditary spherocytosis).
K, Sideroblastic anemia; note the double population of red blood cells. \< **dont' worry about distinguishing from slide)**
L, Sickle cell anemia.
M, Target cells (after splenectomy).
N, Basophil stippling in case of unexplained anemia.
O, Howell-Jolly bodies (after splenectomy).
(From Wintrobe MM et al: Clinical hematology, ed 8, Philadelphia, 1981, Lea & Febiger.)
57
Proportion of RBC to WBC?
1000 rbc: 1 wbc
58
What are hematopoietic cells?
all blood cells made in bone marrow
59
What is too many leukocytes? too few
Too many= leukocytosis
too few= leukocytopenia
60
What are is too many granulocyte? too few?
too many= granulocytosis
too few= agranulocytosis or granulocytopenia
61
Too many neutrophils? Too few?
Too many= neutrophilia
too few= neutropenia
62
Too many eosinophils? too few?
Too many= eosinophilia
too few= eosinopenia
63
Too many basophils? Too few?
too many= basophilia
too few= basopenia
64
too many monocytes? too few?
too many= monocytosis
too few= monocytopenia
65
too many lymphocytes? too few
too many= lymphocytosis
too few= lymphocytopenia
66
too many platelets? too few?
too many- thrombocytosis
too few= thrombocytopenia
67
What is a shift to the left in regards to leukocytes?
excess immature cells in blood
68
What does myeloid stem cell differentiate into? lymphoid stem cells?
Myeloid stem cell- make eosinophil, moncyte, neutrophil, platelet, erythrocytes, basophil
Lymphoid stem cell- makes immunes cells (B,T, NK cells)
69
Leukemia clinical manifestations?
* **Anemia**- not enough RBC
* **bleeding**- not enough plt
* **DIC**- not enough plt
* **infection**- not enough leukocytes
* **bone pain-** using bone marrow with cancer cell replication out of control, causing compression and pain
* **elevated uric acid-** increased cell turnover and increased uric acid production
* **liver, spleen, lymph node enlargmeent**- doing bone marrow processes in other places
* **weight loss**- common in all cancer d/t loss appetite
70
What are generazlied characteristics of acute leukemias? 2 types covered?
* Rapid increase in immature blood cells
* rpaid progression of malignant cells
* decreased production of normal blood cells
* associated with radiation exposure
* worse survival in adults
* Ex- acut lymphocytic leukemia (ALL), acute myelogenous leukemia (AML)
71
What is acute lymphocytic leukemia?
* 80% of childhood leukemia, 90% survival
* for adults, 5 yr survival is between 20-40%
* most common presenting symptoms are fatigue related to anemia, easy bruising r/t thrombocytopenia and bone pain
* lymphadenopahty is a common finding
* susceptible to life-threatening opportunistic infections
* *not making mature lymphocytes or neutrophils*
* mostly B-cell precursors
* associated with **"philadelphia chromosomes"** - **translocation** b/w chr 9&22
* *what bone marrow transplants are for*
* *destory native bone marrow and repoulate with donor*
* *works well with kids*
72
What is acute myelogenous leukemia (AML)
* aka acute myeloid leukemia and acute myelocytic leukemia
* Most deadly leukemia 1% of all cancer deaths
* affects at wide age range, but disease of adults, with a median age at diagnosis of 67 years
* Adult survival rate ~20%, varies from 15%–70% depending on tumor cell cytogenics
* 8 subtypes, M0 – M7, cover all myeloid pathways
* Signs and symptoms of AML are diverse and nonspecific
* **Approximately one-third of patients with AML have significant or life-threatening infection when initially seen**
* severe anemia is common
* Leukemic infiltration of various organs (hepatomegaly, splenomegaly, lymphadenopathy),
* Hyperleukocytosis (\>100,000 cells/mm3)
* making way too many leukocytes
73
General characteristics of chronic leukemia
* Build up of relatively mature blood cells
* progress slowly, typically over years
* abnormal cells found in blood
* ex
* chornic lymphocytic leukemia (CLL)
* Chronic myelongenous leukema (CML)
74
What is chronic lymphocytic leukemia?
* B cells- *producing millions of B cells that are identical*
* *if your body ever finds the antigen to that B cell, then it the disease be cleared*
* *have a gazillion useless B cells*
* Hypogammaglobulinemia
* *don't produce any other immunoglobulins besides the ones repeating, so have higher risk of infection*
* affects elderly, median age at dx is 71 yo
* most common leukemia in adults- rarely occurs in children
* median survival for patients diagnoses with CLL is 8-10 years
75
What is chronic meylongenous leukemia?
* aka chronic myeloid, myelocytic, or granulomatous leukemia
* average age at dx is approx 64 years
* philadelphia chromosome
* poor survival
* blood smear show mature neutrophils, some metamyelocytes, and a myelocyte \<***he said we didn't need to know speicfic cell types, just know they're will be lots of leukocytes***
76
What is a Philadelphia chromosome?
Schema of the Philadelphia (Ph) translocation (+) seen in chronic myelocytic leukemia. The Ph1 chromosome results from an exchange of materials between chromosomes 9 and 22—that is, t(9;22)(q34;q11). Because chromosome 22 gives up much more of its long arm than that translocated to it from chromosome 9, chromosome 22 becomes much abbreviated and is known as Ph1.
This is seen in Acute Lymphocytic Leukemia (ALL) and Chronic Myelogenous Lymphoma (CML)
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What is multiple myeloma?
* Plasma cell myeloma- a single clone of plasma cells that produce a monoclonal immunoglobulin
* multiple myeloma accounts for approx. 10% of hematologic cancers and 1% of all cancers in US
Symptoms include
* Bone pain & hypercalcemia
* Anemia, thrombocytopenia, neutropenia
* Infections- *high plasma antibody but it's not antibody that's useful.*
* *no neutrophil/naive b cells to fight off infection*
* High serum antibody concentration and low serum albumin concentration
* *case where albumin is LOW but not liver problem*
* *liver sees plenty of protein, and doesn't release more albumin*
* Bence-Jones proteins (Ig light chain) in urine
* *making so much antibody that some light chain gets away from heavy chain?*
* *light chain small enough to get through GBM*
* *End up with bence-jones in urine (light chains that go through BM)*
* *Heavy chains that get stuck in GBM attract neutrophils/macrophages and damages GBM causing renal failure*
* renal failure occurs in up to 50% of patients
* Will see hollowing out of bone marrow in skull from plasma cells replicating
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What is lymphadenopathy?
something has caused all lymph nodes to expand
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What is Hodgkin's lymphoma?
* B cell neoplasm- arises in lymph node- 5 subtypes
* about 10% of all lymphomas
* **spreads contiguously to neighboring lymph nodes**
* **Reed-Sternberg cells, pathgnomonic for Hodgkin's lymphoma**
* ****binucleate cell with large, inclusion-like nucleoli and abundant cytoplasm
* painless swelling of involved lymph nodes
* treatable with good survival rate- 20 yr survival rate \>90% for young people
* peak incidence in young adults (15-34) and adults \>80 yo
* infective (epstin barr virus), genetic and environmental associations
* most useful diagnostic test in patients with suspected lymphoma is lymph node biopsy
* lympadenopathy in predictable locations including the neck and anterior mediastinum
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What is non-hodgkin's lymphoma?
* A heterogenous colleciton of lymphomas that are not Hodgkin's lymphoma
* about 90% of all lymphomas
* vary greatly in symptoms, aggressiveness and mortality
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What are common and uncommon lymph node sites for Hodgkin lymphomas
Common
* axillary nodes
* cerivcal supraclavicualr nodes
* retroperiotenal nodes
* inguinal nodes
uncommon
* epitrochlear and brachial
* mesenteric
* popliteal
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What cells are affected in acute lymphocytic leukemia?
B&T cells
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What cells are increased in acute myelongenous leukemia?
granulocytes, megakaryocytes, erythrocytes
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What cells are increased in chronic lymphocytic leukemia
B cells
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What cells are increased in myeloma
plasma cells
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What cells are increased in hodgkin lymphoma?
B cells
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What cells are increased in non-hodgkin lymphoma?
B&T cells
Patho Test 3
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