hemopoesis pt 2 Flashcards
Hematopoietic System
responsible for?
components?
Blood cell forming system
composed of:
Lymph tissue
Bone Marrow
Red bone marrow
Yellow bone marrow
which marrow repsonsible?
hematopoesis
Process in which red and white blood cells are
produced
Red bone marrow
when does yellow marrow form
about 4 yrs old, will replace all reed aside from that in flat bones
Hematopoietic Bone Marrow locations in the Adult
Vertebrae
Ribs
Sternum
Ilia
Erythrocytes
formed via?
Formation Regulated by?
__% of RBCs replaced daily
Life span?
Erythropoiesis
Regulated by kidneys-Erythropoietin (released with decreased O2)
1% of RBCs replaced daily
Life span-120 days (4 months)
Development of Blood Cells from
Hematopoietic Stem Cell to Mature Cells diagram
Reticulocytes
what is in cytoplasm?
Normal range:
Indicator of?
Reticulocytosis?
Reticulocyte count should be?
Immature red blood cells
Reticular network of RNA in cytoplasm
Normal range: 0.5% to 1.5%
Indicator of bone marrow activity
Reticulocytosis – elevated number of reticulocytes in blood
Reticulocyte count should be appropriate to the clinical situation
stages of erythropoesis?
normal values of RBC, platlets, WBC
peripheral blood examination
done via phlebotomy
Erythrocytes – 4.0 – 5.5 million / mm3
Thrombocytes – 150 - 400 thousand / mm3
Leukocytes – 5 – 10 thousand / mm3
how should normal RBC appear on blood smear
biconcave and 7-8 microns
Hemoglobin and Hematocrit Values for males and females
Hematocrit - percent
Males 40 - 54%
Females 37 - 47%
Hemoglobin – grams per deciliter (100ml)
Males 14 - 18
Females 12 - 16
what is serum
plasma-clotting factors
blood components, %
hematocrit
measures RBC V as a % of the total V
RBC count
total number RBC in whole blood
hemglobin measure
measure Hb in blood which reflect RBCs
leukocytes measure
combined total of all types of WBC, can be broken down to individual cell types
Adult Hematopoietic Bone Marrow in the Adult can be used to?
examine potential dx: MM, leukemia and metastesis
Bone Marrow Aspiration
and Biopsy
Posterior superior iliac crest, sample stained and viewed
Hemoglobin strucutre components
heme and globin
Heme
non-protein portion of Hb
Iron porphyrin - 4 pyrrole rings + iron
forms?
Globin
protein portion
HbA (Adult Hb) – 2 alpha, 2 beta
HbF (Fetal Hb) – 2 alpha, 2 gamma
normal adult RBC contain which form Hb mainly
HbA
what must Fe charge be in Hb
2+
Terminology for Reduction
in the Number of Cells
Erythrocytes
(Leukocytes
(Thrombocytes )
Erythrocytes – anemia, erythropenia
(Leukocytes – leukopenia)
(Thrombocytes - thrombocytopenia)
Descriptive Terms for Erythrocytes
cell size and hb content (chromic)
causes?
RBC cell size classes
Normocytic
Macrocytic – B12, Folate deficiency
Microcytic – Iron deficiency
Hemoglobin content classes
Normochromic
Hypochromic
most common anemia seen?
Fe def- microcytic hypochromic
Anemia
A reduction in?
oxygen carrying capacity?
A reduction in the erythron – a reduction in the total red cell mass
below normal limits
Reduction in the oxygen carrying capacity of the blood leading to
tissue hypoxia
anemia diagnosed based on?
Usually diagnosed based on:
Inadequate numbers of erythrocytes (low hematocrit - the ratio of packed red cells to total blood volume)
Inadequate level of hemoglobin – the hemoglobin concentration of the blood
anemias can be due to a disbalance btwn?
RBC production and destruction
3 ways anemias occur
Increased RBC destruction
Decreased RBC production
Blood loss
Clinical Features of Anemia
skin
energy
breathing
cardio
nails
tongue
Cognitive
extremities
Headache
Pallor – pale skin and mucosa
Lethargy – lack of energy, fatigue, weakness
Dyspnea – labored breathing, SOB
Tachycardia, arrhythmia, chest pain
Koilonychia - spoon-shaped nails
Atrophic glossitis
Cognitive problems, dizziness
Cold extremities
Headache
why fatique with anemia?
a person with a low hematocrit cannot carry enough oxygen in the blood to meet energy demands.
Weakness, malaise, and easy fatigability.
why tachycarida with anemia?
Increased heart rate - compensates for the low oxygen carrying capacity of the blood
why SOB with anemia
Shortness of breath / increased respiratory rate – compensates for the poor delivery of oxygen to the tissues.
Dyspnea on mild exertion.
why low bp with anemia
Low blood pressure – a decrease in blood viscosity directly lowers total peripheral resistance to the flow of
blood, thus lowering mean arterial blood pressure
why pale skin with anemia
- hemoglobin is bright red when oxygenated and less red when deoxygenated. Because the redness
of skin is due to the redness of blood, the skin of an anemic person (who has less oxygen in the blood) will be
less red (paler) than the average person
why headache with anemia
Central nervous system - hypoxia can cause headache, dimness of vision, and faintness
hw can anemia lead to cardiac failure
Cardiac failure can develop and compound the tissue hypoxia caused by the deficiency of O2 in the blood
Anemias of Increased Blood Destruction
Sickle cell anemia
Thalassemia
Erythroblastosis fetalis
G6PD deficiency
Malaria
dx vs trait? genetics?
Sickle Cell Anemia
A hemoglobinopathy
Inherited, mis-sense mutation of beta chain
A single AA substitution of valine for glutamic acid
Forms a new, abnormal hemoglobin, Hemoglobin S - HbS
Sickle cell disease – homozygous HbS
Sickle cell trait - heterozygous, a less serious condition
HbS homo vs hetero
Individuals with sickle cell trait (heterozygous for HbS) have a survival
advantage in malaria-endemic areas
Homozygous normal – increased mortality due to malaria
Heterozygous HbS – survival advantage
Homozygous HbS – increased mortality due to sickle cell disease
About 8% of African Americans are heterozygous (sickle cell trait)
1 in 600 African Americans are homozygous (sickle cell disease)
dif in hetero?
Behavior of HbS in
Hypoxic Conditions
HbS molecules polymerize when deoxygenated, forming HbS aggregates
Cytosol changes from a freely-flowing liquid to a viscous gel
With continued deoxygenation, HbS aggregates form long, needle-like fibers that distort the red cell shape
Sickle cell trait – HbA interferes with HbS polymerization in the heterozygous condition
Red cells do not sickle except under conditions of profound hypoxia
anemia? vascular? common locations? spleen?
Clinical Effects of Sickling
in Sickle Cell Anemia
Hemolytic anemia - chronic hemolysis leading to jaundice and phagocytosis in spleen
Microvascular occlusions - sickle cells becone arrested during transit through the microvasculature
Vaso-occlusive crises (pain crises)-episodes of hypoxic injury and infarction that cause severe pain in the affected region: Commonly involved sites: bone, lung, liver, brain, spleen
Autosplenectomy
Clinical Consequences of
Splenectomy
Increased susceptibility to infection with encapsulated organisms
Pneumococcus pneumoniae and Hemophilus influenzae
what can this be seen with?
hair on end radiograph, can be seen with sickle cell anemia and beta thalassemia major
what radiogrpahic anomolies can be seen with SCA
hair in end and step ladder trabeculae
Thalassemia
Group of inherited diseases
Quantitative problem - too few globins synthesized, A or B could be affected
Underproduction of normal globin proteins due to mutations in regulatory genes
can lead to?
tx thalassemia
Regular transfusions – iron
overload – organ damage
bones? spleen? growth? tx?
consequences of thalassemia
Bone deformities – expansion
of marrow space
Splenomegaly - splenectomy
Impaired growth
Bone marrow transplantation
genetics? forms?
beta thalassemia
Two genes involved in making beta chain (one from each parent)
Severity depends on number of affected beta chain genes
One gene – beta-thalassemia minor - beta-thalassemia trait= Mild disease
Two genes – beta-thalassemia major (Cooley’s anemia)= Severe disease
genetics? forms?
Alpha Thalassemia
Four genes involved in making alpha chain (two from each parent)
Severity depends on number of affected alpha chain genes
One gene – asymptomatic carrier
Two genes – alpha-thalassemia minor - alpha-thalassemia trait= Mild disease
Three genes – hemoglobin H disease= Moderate to severe disease
Four genes – alpha-thalassemia major – (lethal)
what can happen in marrow of mid face with thalassemia
compensatory hyperplasia
what can be seen radiograpically with thalassemia
hair on end like SCA
ABO Blood Group Incompatibility leads to?
ABO mismatch leads to intravascular hemolysis
Antibody-coated erythrocytes destroyed by both complement-mediated lysis and by phagocytosis in spleen
Ab, Ag
blood groups
Blood Type Distribution ABO
Type O – 45%
Type A – 42%
Type B – 10%
Type AB – 3%
Blood Type Distribution Rh
Positive - 85%
Negative - 15%
Erythroblastosis Fetalis
Hemolytic Blood Rh-Mediated Hemolytic Disease of the Newborn
if known mom - and baby + what can be done?
Erythroblastosis Fetalis:
1st Pregnancy at Delivery
Rh- mom
Rh+ fetus
Fetal RBCs cross the placenta and
enter the maternal circulation
during birth trauma
Prophylactic anti-Rh (D) immune
globulin (Rhogam) within 72 hours
of delivery
Rhogam lyses fetal RBCs in the
maternal circulation – effectively
removing any available antigen,
so the mom doesn’t develop anti-
Rh antibodies
baby not harmed
Erythroblastosis Fetalis:
2nd Pregnancy at Delivery
Rh- mom, with anti-Rh from prior
pregnancy
Rh+ fetus
Anamnestic response rapidly
produces anti-Rh (IgG)
Anti-Rh IgG crosses placenta
and lyses fetal RBCs
Rh-mediated hemolytic disease
prevention of Erythroblastosis Fetalis
Rhogam: Rhesus Immune Globulin - RhIg
Immunoglobulin
Administered to Rh-negative women after pregnancies in which they carried Rh-positive fetuses
Anti-D antibodies
high levels of what are seen in fetus? can deposit where?
Erythroblastosis Fetalis effects in fetus
Hemolytic anemia in utero
Rh-negative mother develops antibodies against Rh-positive erythrocytes of fetus
Antibodies cross placenta and hemolyze fetal erythrocytes
High levels of bilirubin and biliverdin
Deposition in developing teeth
Only primary teeth affected
abnromal cell in periphery? increased? brain? dental?
Clinical Features of Erythroblastosis Fetalis seen in fetus?
Erythroblasts in peripheral blood
Hyperbilirubinemia
Kernicterus (bilirubin encephalopathy) if bilirubin reaches a high
levels
Developmental dental defects reported- enamel hypo and staining
genetic, demo, symptoms
Glucose-6-Phosphate
Dehydrogenase Deficiency
X-linked disease; most common human enzyme defect (African-American male population)
Most are asymptomatic; at risk for non-immune hemolytic anemia upon exposure to oxidative stress
Oxidative stress: infections, drugs (aspirin)
G6PD importance
G6PD / NADPH / Glutathione pathway - maintains supply of reduced glutathione to scavenge free radicals (anti-oxidant)
Red cells sustain damage from oxidizing free radicals (phagocytosed in spleen), decreased RBC
individuals with what are G6PD def. (aside from mutation)
All individuals with Favism (hemolysis due to Broad Beans(fava)) are G6PD deficient
G6PD can give a survival advantage where
endemic malaria environments
superficial manifestation of G6PD def
juandice
Malaria
caused by? vector/resivoir?
Reproduction in? causes?
type of anemia?
morbidity, mortality?
Malaria
Protozoal disease – primarily Plasmodium falciparum
Female Anopheles mosquito vector, human reservoir
Reproduction in red cells – showers of organisms produce shaking, chills and fever
Hemolytic anemia
High morbidity, mortality
Anemias of Decreased
Red Blood Cell production
Iron deficiency anemia -microcytic, hypochromic
Pernicious anemia (B12 deficiency) - macrocytic
Folic acid deficiency anemia - macrocytic
Aplastic anemia
fe def anemia appearence on smear
microcytic and hypochromic
Iron Deficiency Anemia
Most common?
Lack of Fe most common?
RBC app
Seen most often in? why?
Treated with?
When in males, suspect what?
Most common anemia in US
Lack of Fe most common nutritional
deficiency in the world
Microcytic, hypochromic
Seen most often in females – more iron lost in menses than replaced by nutrition
Treated with iron supplements
When in males, suspect internal
bleeding
tongue with fe def
atrophic
fe de f anemia most common presentation
middle aged female with profound anemia
causes of fe def
Dietary lack
Impaired absorption
Increased requirement
Chronic blood loss
how can infants be fe def
breat feeding
how cna children be fe def
poor diet
males and females
how can adults be fe def
Males - peptic ulcer
disease
Females - menorrhagia or
pregnancy
developed vs undeveloped
elderly fe def causes
Colonic polyps / colon adenocarcinoma in Western world
Hookworm infection in developing world
Laboratory Measurements of Iron Status
Serum ferritin
Total iron binding capacity (TIBC)
% saturation
Serum iron
Serum ferritin measures reflect what?
Serum ferritin – reflects iron stores in bone marrow
macrophages and liver
Total iron binding capacity (TIBC)
measure of transferrin
molecules in blood
% saturation –
percent of transferrin molecules bound by
iron (nl = 33%)
Serum iron
Serum iron – measure of iron in the blood
demo? what is def? mucosa? esphogus? risk of/where?
Plummer-Vinson Syndrome
Scandinavian, Northern European women
Severe Fe-deficiency anemia
Mucosal atrophy - atrophic glossitis
Esophageal webs - dysphagia
Increased risk for squamous cell carcinoma: Esophagus, Oropharynx, Posterior Oral Cavity
Macrocytic Anemia forms
Pernicious anemia (B12 deficiency) - macrocytic
Folic acid deficiency anemia - macrocytic
what is def in pernicious anemia
B12
absorption req? what is formed/absorbed where?
Vitamin B12 (Cobalamin) Metabolism
Absorption of vitamin B12 requires intrinsic factor, which is secreted by the
parietal cells of the stomach
Cobalamin – Intrinsic Factor complex
absorbed in the ileum
type of dx? B12 req for?
Pernicious Anemia
Autoimmune disease
Not due to dietary deficiency of B12
A form of megaloblastic anemia caused by autoimmune gastritis and failure of intrinsic factor production leading to vitamin B12 deficiency
Loss of ability to absorb Vitamin B12
Vitamin B12 (cobalamin) required for normal folate metabolism and DNA synthesis
food sources b12
milk, poultry, eggs, meat, shellfish
B12 roles
maintenence CNS and RBC production
tongue w pernicious anemia
atrophic and ulcerative
lips/ventral tongue with pernicious anemia
red
folate needed for?
folic acid def
Megaloblastic anemia
Dietary deficiency of folic acid
Folate required for DNA synthesis
aplastic anemia
Marrow aplasia secondary to supression of multipotent myeloid
stem cells (erythrocyte, leukocyte and thrombocyte series), resulting in pancytopenia
what can cause aplastic anemia
May be caused by known myelotoxic agents (eg. whole body radiation)
Antineoplastic drugs (alkylating agents, antimetabolites)
Benzene
Chloramphenicol
aplastic anemia pathogenesis may involve
T cell attack on myeloid stem cells
prognosis aplastic anemia
unpredictable
tx aplastic anemia
bone marrow transplant and transfusions
anemias of blood loss
Gastrointestinal bleeding
Hemoptysis (coughing up blood)
Epistaxis (nosebleed)
Hematuria (blood in urine)
Menstrual blood loss
vomiting? stool?
GI bleeding indications
Hematemasis (vomiting blood)
Melena (black stool)
Hematochezia (red blood in feces).
Menstrual blood loss forms
Menorrhagia (excessive bleeding)
Metrorrhagia (irregular bleeding).
Fecal Occult Blood Test – Stool Guaiac
Screening test for occult bleeding in GI tract
forms?
Polycythemia (Erythrocytosis)
An increase in the RBC mass
can be relative or absolute
Relative polycythemia
dehydration – decreased plasma volume with normal red cell mass
Absolute polycythemia
a true increase in red cell mass
can be primary or secondary
Primary absolute polycythemia (polycythemia vera)
Erythropoietin-independent
Acquired, clonal stem cell disorder (a chronic myeloproliferative disorder)
EPO? response to? examples?
Secondary polycythemia
Erythropoietin-dependent
Compensatory response to tissue hypoxia: Chronic lung disease, Cigarette smoking, Residence at high altitude, Paraneoplastic syndromes
