Hematologic Pathology Flashcards
platelets
cytoplasmic fragments of megakaryocytes
fxn: stop bleeding
lifespan = 8-9 days, 30% of numbers are on reserve in spleen
eyrthrocytes
RBCs
most numbers
life span: 3-4 months in circulation
large surface area (surface:volume) so they can quickly pick up and dump oxygen
flexible: can get into small capillaries
where are WBCs produced?
Bone marrow, lymph nodes and spleen
types of WBCs
- neutrophils
- lymphocytes
3, eosinophils - basophils
- monocytes
neutrophils
45-70%
actively phagocytic cells (fights foreign invaders)
dominate in acute inflammation and bacterial infections
lymphocytes
35-40%
long living, predominate in WBC of children
rotation between circulation and lymph nodes
predominate in a viral infection
eosinophils
5-10% (MINOR)
when they are high: NAACP
N= neoplasm A= allergies A= airway disease C=connective tissue disease P= parasites
basophils
3-7% (LEAST common)
allergic reactions
histamine and heparin release
monocytes
3-5%
actively phagocytic cells
become macrophages when they move from the blood to the tissues
hematopoietic stem cells
progenitor cells that are found in bone marrow
common “ancestor” for all blood cells, growth factors/hormones differentiate
thrombopeotin
stimulates platelet production
produced by liver, kidney, skeletal muscle, bone marrow
low platelet count stimulates thrombotic production
hormones that stimulate WBC production
G-CSF
GM-CSF
IL3
what hormone stimulates RBC production?
erythropoeitn
Erythropoetin
RBC production hormone
stimulated for release by kidney
what stimulates eruthropoetin release from kidney?
low peripheral blood O2
problematic bc may promote blood viscosity (decreasing blood flow rate)
hypoxia can have other causes (such as smoking) that could be harmed by increased viscosity
most important white cells disorders
malignancies
spleen functions
identification and removal of tagged cells (cells with Igs)
storage of platelets
removal of red blood cells (damaged or old)
what causes damage to the spleen
mononucleosis
liver disease
cancer
if damaged, it won’t weed out potential invaders or rupture during trauma
sequelae if spleen is removed
immunocompromised
especially sensitive to encapsulated organisms (spleen is best at grabbing these) (meningitis nicesiaria, etc.)
cancer that starts in progenitors cells of WBCs
leukemia
When a progenitor cell becomes a leukemic cell:
maturation process is arrested (stops)
cell division is then accelerated and apoptosis is limited
resulting in many copies of immature cells
builds up in the bone marrow and crowd out the normal cells (eventually spread to other cells)
two categories of leukemia
- lymphotic or myeloid leukemia
2. acute or chronic leukemia
leukemias developing from lymphoid cell line
lymphocytic
leukemias developing from WBCs, RBCs, and platelet precursors
myeloid
acute leukemia
leukemias that progress rapidly and are fatal if not treated quickly
chronic leukemia
leukemias that progress slowly, come from more mature progenitors
what typically causes the signs and symptoms of leukemia?
deficiencies of the other cell likes
Main symptoms of leukemia
fatigue dyspnea on exertion stollens nd bleeding gums fevers recurrent infections petechiae
B symptoms of leukemia
occur bc of the malignancy
weight loss, fevers, right sweats, muscle wasting
signs of leukemia
splenomegaly
hepatomegaly
petechiae
pallor
acute lymphocytic leukemia
ALL
most common in children 2-5 yrs (another peak in elderly)
common cause is genetic mutation (haven’t ID what)
Very likely to survive if a child, minimal numbers of adults survive
chronic lymphocytic leukemia
CLL
most common type in US adults
sometimes rapid progression, most cases is indolent
often patient is asymptomatic at time of discovery (accidental finding on routine CBC)
often monitored without specific treatment until it progresses
Acute Myelogenous Leukemia
AML
cancer of any WBC besides lymphocytes
occurs in bone marrow when cells arrest in earliest stage of differentiation and begin proliferating
other cell lines in bone marrow are crowded out (resulting in neutropenia (low other WBCs) anemia, and thrombocytopenia)
more common in developed nations, caucasians
median age is 70 (effects all ages)
blast cell
a primitive, undifferentiated blood cell, often found in the blood of those with acute leukemia
(AML)
Chronic myelogenous leukemia
gradual progression
most often found in older adults
accounts for a small amount of leukemias
philadelphia chromosome
philadelphia chromosome
reciprocal translocation between long arms of chromosomes 22 and 9
CML
patient has this type of leukemia:
- 62 yr old black male
- high serum levels of lymphocytes found on routine labs
- asymptomatic
Chronic lymphocytic anemia
patient has this type of leukemia:
- 73 yr old white female
- blasts present in blood
- low neutrophil, platelet, and RBC counts
acute myelogenous leukemia
patient has this type of leukemia:
- 4 yr old hispanic boy
- quick progression
- high lymphocyte progenitor counts
acute lymphocytic leukemia
patient has this type of leukemia:
- gradual progression
- Philadelphia chromosome
chronic myelogenous leukemia
to diagnose any type of leukemia this procedure myst be done
bone marrow biopsy
genetic analysis of WBCs
bone marrow biopsy tells us
definitive diagnostic test
tells us if one cell line is at higher numbers than the others
genetic analysis of WBCs tells us
possible mutations of the cancer cells that may be important for determining treatment
can be targeted by a cancer drug and limits collateral damage
lymphoma
cancer of MATURE lymphocytes
OUTSIDE bone marrow
broad division of lymphomas
Hodgkin’s
Non-Hodgkin’s
how do we diagnose lymphoma?
lymph node biopsy with genetic analysis of specimen
excision of node from: cervical, axilla, inguinal
s/s of lymphoma
lymphadenopathy
hepatomegaly, splenomegaly, or abdominal mass
pruritus
b symptoms
cytopenia symptoms
mediastinal mass
B symptoms of lymphomas
unexplained weight loss
unexplained fever
drenching night sweats
cytopenia symptoms
decreased WBCs, RBC, platelet #s
staging of lymphoma (4)
histology
extent of disease
symptoms and performances
status of patient
once we know the stage, we recommend treatment
treatment for lymphoma
low grade: watchful waiting
higher stage: XT, CXT, bone marrow transplant
multiple myeloma
malignancy of plasma cells in bone marrow and bloodstream
plasma cells overproduce an Ig protein (toxicity) - may cause *acute kidney injury *
produces lytic lesions in the bone, causing pathologic fractures
CBC results of multiple myeloma
plasma cells crowd out the other cell lines in bone marrow
causes anemia, neutropenia, thrombocytopenia
multiple myeloma diagnosis
monoclonal spike on serum and urine protein electrophoresis (SPEP and UPEP)
normal: high albumen spike, low Igs
MM: high albumen and one high Ig (two peaks)
multiple myeloma Ig production
may cause acute kidney injury (blocks up the tubules so no filtration or waste removal)
hypervicosity
amyloidosis (abnormal` protein folding)
erythropoesis
development of RBCs
only occurs in bone marrow
what does an RBC synthesize as it grows?
Hemoglobin
released from bone marrow into blood when 80% done
reticulocyte
RBC released into blood prior to maturation
has about 80% of its Hg, matures in 24 hours
hemoglobin
4 iron and 4 protein chains that form a stable porphyrin ring
components of adult HgB
2 alpha and 2 beta chains
components of fetal HgB
2 alpha and 2 gamma chains
these gamma chains have a higher O2 affinity so they suck up more oxygen
at birth: 50% adult, 50% fetal but by 6 months, they are all adult
raw materials required for erythropoiesis
- iron
- b-12, folate, and proteins
- adequate bone marrow
how do RBCs get iron?
via absorption from dietary intake in duodenum
recycled from breakdown of RBCs (most)
how do RBCs get B-12, folate and other proteins?
absorption from the gut
via diet
what is the site of RBC construction?
bone marrow
decrease in RBC mass?
anemia
s/s of anemia
fatigue palor/paleness fainting/dizziness altered menta status tachycardia/palpitations SOB
what test uncovers anemia?
CBC
decreased HgB and Hct
classifications of anemia
based on RBC size – via MCV
microcytic
normocytic
macrocytic
or by color (hypo chromic and normochromic) – not common bc subjective
causes of normocytic anemia
- decreased production capability of marrow
- decreased stimulation to produce RBCs
- increased peripheral destruction of RBCs
anemia of chronic disease, chronic renal failure, hemolytic anemia, blood loss, aplastic anemia
microcytic anemia
small size
due to abnormalities in hemoglobin production (inc hemoglobinopathies)
iron deficiency, thalassemia
decreased RBC production capability of marrow
causes normocytic anemia
may be due to not enough space
aplastic anemia, anemia of chronic disease
decreased stimulus to produce RBC
causes normocytic anemia
caused by chronic kidney disease
not enough stimulus to produce enough
increased peripheral destruction of RBCs
causes normocytic anemia
hemolytic anemia, hereditary spherocytosis
bone marrow works fine, but RBC lasts less time before they die
macrocytic anemia causes
due to vitamin deficiencies (B-12, folate)
may be due to drugs that inferred with DNA synthesis (aren’t able to mature properly)
clonal proliferation in bone marrow (myelodysplasia)
liver disease, alcoholism, hyperthyroidism, drugs (sulfa, AZT, CTX)
ferritin
protein stored with iron in the liver
stays here until it is transported to marrow
transferrin
protein responsible for transport of iron from liver to marrow
acid environment encourages absorption
iron
b-12
what causes iron deficiency to develop?
- inadequate iron intake in the diet (esp. vegetarians, breast fed infants)
- infants during periods of rapid growth
- inadequate re-utilization of iron present in red cells due to chronic blood loss (causes heavy menses, vascular disorder of colon)
PICA
common in iron deficient patients
craving for/eating clay, dirt, ice
common in pregnant women, low SES
iron deficient anemia may produce which conditions?
PICA
restless legs
esophageal webs
Iron studies comprise which tests (+definition)
- iron level (FE concentration in serum)
- serum ferritin (est. iron stores)*
- transferrin (amount of iron transporting peptide)
- % saturation (%of transferrin bound to blood)
*serum ferritin is interpreted with caution bc can be influenced by infection and inflammation
what pattern will show on iron studies in patient with iron deficiency
- iron level = LOW
- serum ferritin = LOW
- transferrin = HIGH (increases to catch more)
- % sat = LOW
thalassemias
genetic mutation resulting in decrease in production of alpha and beta chains
will have over production of other chains that it doesn’t make (more beta cells if alpha def., etc.)
often found in patients of african, asian, or mediterranean ethnicities
can vary in severity
extra medullary hematopoiesis
occurs in major thalassemias
inadequate hematopoiesis forces areas of the bone to try and produce RBCS – unfortunately this is not the problem, instead it is an inability to transport oxygen (genetic not space issue)
causes bossing of the skill, engaged maxilla, saddle nose
massive hepatosplenomegdaly (enlarged liver)
wasting of extremities
short stature
thalassemia treatment
resource rich: hyper transfusion therapy (lifetime blood transfusions to minimized hematopoietic stimulation)
may cause iron overload
in poor countries: terminal
mesoblastic anemia
form of macrocytic anemia
due to impaired DNA synthesis that therefore causes more cytoplasm to accumulate than normal
labs for macrocytic anemia
B-12 and folate level check
may do TSH check in liver
folate deficiency
comes from green leafy veggies
common in those with poor nutrition - alcoholics and those in low SES
causes macrocytic anemia
b-12 deficiency
comes from animal protein
important for hematopoietic fxn and nervous fxn
absorbed from terminal ileum when complexed with INTRINSIC factor (via acid producing stomach lining)
two types of b-12 deficiency
true b-12 def.
pernicious anemia
who gets TRUE b-12 deficiency
vegetarians
Chron’s disease
chron’s disease and B-12 def
inflammation of the ileum so can’t absorb B-12
pernicious anemia
body produces B-12 but it has autoantibodies, lack of intrinsic factor, Abs bind to the B-12 instead
common in patients with atrophy of stomach lining (elderly), autoimmune dx, and removal of lining (ulcer, bypass)
why may a healthy person experience normocytic anemia
following a trauma (including C-section)
surgical procedure
anemia of chronic disease
decreased bone marrow ability to produce RBCs, Normocytic
caused by chronic inflammatory conditions (infection, autoimmune, malignancy), causes issue with ferritin, interferes with normal iron transport bc more iron is in storage
generally develops slowly and well tolerated
goal is to treat underlying disease causing the inflammation
aplastic anemia
decreased BONE MARROW ability to produce RBCs
Normocytic anemia
severe damage to the bone marrow that destroyed stem cells, kills of progenitors
causes rapid anemia
may be caused by drugs, medications, toxic chemicals, CTX, XT, or autoimmune
workup for anemia of chronic disease
iron: NORMAL
transferrin: NORMAL
serum ferritin: NORMAL/increased (bc of inflammation )
% sat: NORMAL, increased
decreased stimulation of Red blood cells and anemia
caused by advanced chronic kidney disease
erythropoietin is not produced
also produces 2ndary HTN
how is decreased stimulation of RBCs different than anemia of chronic disease?
anemia of chronic disease is an issue with iron transport, not enough in the blood more in storage, this is bc the kidney is not releasing erythropoietin so cells just aren’t being produced
ABCDEs of peripheral RBC destruction in the blood
A: Air (low O2) B: Box (shape) C: Synthesis D: defective enzyme E: hostile environment
hemolytic anemias caused by defective Hg
ex. disease sickle cell
due to genetics, produces Hgb S instead of Hgb A
abnormal HgB S deforms the RBC in crisis plugs capillaries if O2 is low
capillary plugging results in bone and organ damage, and rapid destruction of sickled cell causes anemia
hemolytic anemias caused by shape problems
hereditary spherocytosis
congenital abnormalities in shape and flexibility (ALL RBCs)
RBCs become trapped in spleen and recycled prematurely
chronic low grade hemolytic anemia
hemolytic anemias caused by defective Hg synthesis
alpha and beta thalassemia
person can’t produce (homo/major) or reduced production (minor) of alpha or beta HG chains
the chain that is produced accumulates in RBCs and shortens life span
hemolytic anemias caused by defective RBC enzyme
G6PD Deficiency
G6PD metabolizes glucose and protects Hg from oxidation
total absence (male) or diminished presence (female) of enzyme means that susceptible during stressful situations
hemolytic anemias caused by hostile environments
autoimmune Hemo. anemia
activation against RBC offing following drug injection or part of autoimmune disease, occurs without warning
sudden, onset hemolytic anemia
RDW
red cell distribution
reads CBC and gives a bell curve of size distribution
narrow bell curve = MCV is truly value
wide bell curve = could mean that you have multiple anemias, must broaden scope and do other tests
polycythemia
when the Hgb/Hct are above normal (too many RBCs)
two causes:
- polycythemia vera
- secondary polycythemia
polycythemia vera
hyperplasia of RBC bone marrow precursor
abnormal turning on of genes
secondary polycythemia
erthrocytosis bc of low oxygen levels
consequences: increased blood viscosity (could cause eventual CVA in CNS)
hemochromatosis
genetic inability to excrete iron
iron overload causing O2 radical damage
iron disposition in organs to cause failure
treated with constant phlebotomy (blood is normal, can be donated)
4 tests for evaluation of hemolytic anemia
- serum haptoglobin (decrease)
- LDH (increase)
- reticulocyte count (increase)
- peripheral blood smear
separate of CBC
hemolytic anemia test definite + result:
Serum haptoglobin
haptoglobin = plasma protein that clears HgB
reduced if hemolysis
hemolytic anemia test definite + result:
LDH
lactate dehydrogenase
intracellular enzyme, marker of lysis
elevated if hemolysis
hemolytic anemia test definite + result:
reticulocyte count
normal is 1%
increases if there is hemolytic anemia bc bone marrow is trying to make more
hemolytic anemia test definite + result:
blood smear
will show that there is more abnormal shape cell or fragments
if there are fragments = hemolysis
