IDA develops slowly through 3 overlapping

stages:
1bodys iron stores for erythrooesis are
depleted
2erythropoesis begins to be affected at the
Stages of Iron deficient anemia same time that the hemoglobin content of the
RBCs being formed is lowered
3when small, Hb deficient RBCs enter the
circulation

1. Serum ferritin and iron concentration will be

Laboratory tests to confirm LOW (but, acute phase reactant, may go up for
other reasons)Serum iron binding capacity is
IDA HIGH
2. Bone marrowcan use storage Fe, but this is
painful, cumbersome
3. Treatment

Microscopic Histopathology Hypochromia refers to lowered Hb content in

RBCs (MCHC)
findings for IDA Microcytic (MCV)
These findings suggest that laboratory tests
should be done to confirm IDA

Cold, pale extremitites

Generalized pallor of skin and mucous
membranes
Signs of anemia Jaundice (suggest hemolytic anemia)
Chelosisfissuring at the angles of the mouth
(can have other causes)
Koilonychia (concave nails)

0.01-0.05% of bone marrow population

self-renew and differentiate
pluri: self-perpetuating pool
Hematopoiesis: Stem cells multi: can become either lymphoid or
Pluripotential, multipotential, progenitor, myeloid cells
precursor progen: commited to a cell lineage
precursor: can prolife and develop into
myeloid lineage
 1. begins in fetal yolk sac
2. shift to liver
Embryology of RBCs 3. later forms in spleen
4. term, forms in bone marrow
5. as adult, most occurs in axial skeleton

1. fat cells, macrophages, endothelial cells,

Bone marrow stroma lymphocytes, and fibroblasts
1. types of cells 2. Collagen, adhesion proteins, growth factors
2. What else? such as G-CSF, GM-CSF, EPO

1. proerythrobastintense blue, round nucleus

2. basophilic erythroblastintense blue, condensed
chromatin
3. polychromatophilic erythroblastgrayish cytoplasm
Stages of erythropoiesis? due to hb, smaller nuleus
4. orthochromatic erythroblastreddish, small nucleus
5. reticulocyteno nucleus, still has mito and RNA
6. mature erythrocyte

1. myeloblasthigh N:C ratio

2. promyelocyteprimary (purple) granules
3. myelocytenucleus may be eccentric, cytoplasm
may have pink granules
4. metamyelocyteskidney bean shaped nucleus
Stages of Granulopoiesis? 5. bandhorseshoe shaped nucleus
6. PMNlobular nucleus
--first line of defense for microorganisms, chemotatic,
opsonins, lysosomal enzymes
KNOW: hydrogen peroxide, superoxide, halides

Monoblasts mature into monocytes. Become

part of mononuclear phagocyte system in
tissue.
Monocytopoiesis Half life is 70h
Chemotaxis, phagocytosis, antigen
presentation, IL-1 and TNF relase (eg due to
endotoxins),
 Etoposide (VP-16), teniposide (VM-26)
These mature into multilobed giant cells by
Megakaryocytopoiesis endomitotic divisions. Granular cytoplasm,
with platelet containing ribbons

Large granules stain red with eosin due to

basic proteins
Bilobed nucleus
In tissue
Eosinophils IgA receptors, toxic cationic proteins, kill
parasites, cause allergic reactions
Chemotaxis, phagocytosis,
Immediate type hypersensitivity

Blue-black granules with histamine

Allergic reactions
Basophils Immediate type hypersensitivity
Inflammatory responses

Based on symptoms, NOT numbers

1. shock
2. surgery
When are transfusions necessary? 3. angina pectoriscornonary insufficiency, chest
What are the risks? What happens? pain on exertion
Risks: Hep B, HIV, Hep C even with testing
Hb increases by 1g and hematocrit rises by 3% with
250mls.

Anemia with: 1. marrow problem

1. low reticulocytes 2. ditto
3. rbc destruction or blood lossnormal marrow
2. normal reticulocytes
3. high reticulocytes is accounting for decreased RBCs

The low down on iron
Differential diagnosis for
Macrocytic anemia
3 major causes of folate deficiency
How do you diagnose folate
deficiency?
How do you treat it?
3 major causes of B12 deficiency
How do you diagnose B12
deficiency?
How do you treat it?
What is folate very important for?
How long does the body store it
for?
In most foods
Absorbed in small intestine
Transferringcarrier protein which delivers it to
the marrow
Ferritiniron is stored complexed to ferritin in the
liver, spleen.
The body recycles iron!! Adults tend to keep their
iron around 3g: 2 in erythrocytes, 1 in storage
Because storage is full in adulthood, decreased iron
must be due to loss of blood.
1. Folate deficiency
2. B12 deficiency
Dietary (salads), Malabsorption (illium),
Increased usage (pregnancy)
Dx:
1. Morphology (macrocytic RBCs,
hypersegmented PMNs
2. Serum folatelook for LOW levels
3. Red cell folatelook for LOW levels
Treatment:
1. folate supplement, 1mg a day
Pernicious Anemia (autoimmune anti-parietal cells,
therefore no IF), Malabsorption (illium), Pancreatic
insufficiency (no secretion, no R/IF switch
Dx:
1. Morphology (macrocytic RBCs, hypersegmented
PMNs
2. Serum B12look for LOW levels
2. Neurologic findingsdemyelination of spinal
cord (proprioception, cerebral cx (dementia)
Treatment:
B12 supplement, 1mg a day
B12 is a cofactor (stored for four mo)
Folic acid to dihydrofolate
Without enough folate you dont make
DNA!!
Folate stored for years

B12 absorption
Hemolytic anemiasincreased
RBC degradation, decreased life
span of RBCs. What are clinical
features?
Extravascular vs. intravascular
hemolytic anemai
Laboratory findings for
increased RBC production
Laboratory evidence for
increased RBC destructoin
Mech:
MeatB12R factor from salivary glands
binds to B12in duodenum, IF from stomach
switches with R factorpancreatic secretions
are required for thisB12 is absorbed at
terminal illium
Splenomegaly
Jaundice
Icterus (yellow discoloration of sclerae)
Ankle ulcers
Aplastic crisis from Parvo B19 (infect and
lyse RBCs)
Pigmented gallstones composed of bilirubin
Tea colored urine
Increased requirement for folate
1. Extravascular: macs in spleen, liver, marrow
remove damaged RBCs with Abs on them.
Hemolysis occurs in cells of RE system. Little
free Hb released.
2. Intravasc: destroyed directly in vasculature.
Free hb released into circulation.
Elevated reticulocyte count, polychromasia
Elevated MCV, RDW elevated
Erythroid hyperplasia in bone marrow
frontal bossing; marrow (skull, ribs, and
long bones) expands because of increased
erthropoiesis
elevated LDH due to cell death
elevated unconjugated bilirubin aka indirect
bilirubin
lower levels of serum haptoglobin; it binds to hb and is
rapidly cleared
Hemoglobinemia more hb than can be bound to
haptoglobin
Hemoglobinuria free hb in urine (reddish ur.)
Hemosiderinuria hb in urine taken up by tubular cells and
changed into hemosiderin
Schistocytes, spheerocytes, bite cells or blister cells
 Defects in membrane skeleton proteins
Types of congenital hemolytic hereditary spherocytosis
Defects in enzymes involved in energy
anemia
productionGP6D deficiency
Defects in hb structure or synthesis--

Defects in spectrin or ankyrin

Hereditary Spherocytosis
People tend to be of European background
Blebs are pinched off by macs in
spleendecreased size of cell, lose biconcavity
Symptoms: splenomegaly, ankle ulcers,
pigmented gallstones, INCREASED
OSMOTIC FRAGILITY, increased MCHC
Tx: folate, splenectomy has a risk for OPSS
overwhelming post-splenectomy sepsis
Aerobic metab requires G6PD. This is required for
detoxification of oxidative stress and getting rid of
methemoglobin
Heinz bodies methoglobin that denatures and ppcs out

Red cell metabolic enzyme Type B=most prevelant, Type A=20% of healthy Af-Ams
have this.
defects Af. Mutant A- unstable and loses activity;
Mediteranian always low base activity
X-linked
Clincal features: triggered by drugs, infections, maximal
7-10d of drug exposure
Tx: avoid oxidant agents, folate repletion

Sulfa drugs, chloramphenicol

Dapsone
Oxidant drugs/chemicals which Quinine and chloroquine, primiaquine

cause hemolysis
Vitamin K
Fava beans
Naptha compounds--mothballs

antibodies bind to red cellsRE system via Fc

Rspherocyte formation
1. warm antibody mediateddrug induced, reacts at 37,
Immune mediated hemolysis does not cause red cell agglutination. IgG
2. cold antibody mediatedreact best <32, do cause red
Two types? Hallmark? cell agglutination. IgM
Hallmark: positive coombs test

Looks for antibodies to red cells, comes as a set:
Coombs test 1. Directpts RBCs with goat-anti-human IgG or
2. indirecttest for IgG or C3 inserum
Causes of autoimmune hemolytic
anemia
Clinical Features of autoimmune
hemolytic anemia? Tx?
Drug induced hemolytic anemias
Cold agglutinin
disease/autoimmune hemolytic
anemia. Tx?
Myeloid
C3 inkit
Busulfan
Idiopathic
Complication of SLE, lymphoma, or leukemia
Infections can provoke it
Drugs can induce it
Associated with immune platelet destruction
Evans syndrome
Thiotepa
Fatigue
Pallor
Jaundice
Splenomegaly
Lab: increased reticulocyte, increased bilirubin,
increased LDH, positive coombs, sphereocytes
Tx: immunosuppression1. corticosteroids,
2. splenectomy, 3. cyclophosphamide
Carmustine (BCNA
Innocent bystander mechanism antibodies +
drug land on RBCsRE system clears; drug
must be present
Hapten mechanism antibodies against durg +
RBC suface
True autoimmune mechansism antibody
production continues even in absence of drug
Dacarbazine
IgM!! Directed against I or i antigen
Agglutinatecyanosis or ischemia in the cold
extremities.
Coombs is + for C3, negative for IgM
Etiology: IgM, Mycoplasm pneumonia,
Mononucleoisis, lymphoproliferative disease
Tx: cold avoidance, mittens, folate repletion
 Non-immune
Microangiopathic Hemolytic anemia (MAHA)
Hallmark: schistocytes-scharp

Chemotaxis, phagocytosis, killing of phagocytosed

bacteria
Fine pink granules
Adherance rolling mediated by selectins, firm adhesion
via beta-2 integrins
Neutorphils Recognition and phagocytosis, make phagosome
Degranulation
Oxidative metabolism and bacterial killing. First NADH
oxidase converts superoxide into hydrogen peroxide.
Within phagosome, myeloperoxidase combines hydrogen
peroxide and chloride to form hydrochlorous acid

Immune regulation
Lymphocytes Hematopoitic growth factors

Physiologic: Neonate, Exercise, Lactation, Pregnancy

Elevated neutrophil count
Acute infection or inflammation
Acute hemorrhage
Non-hemolytic malignancies
Myeloproliferative diseases
Metabolic: uremia, acute thyrotixicosis, diabetic ketodosis
Drugs: G-CSF, GM-CSF, corticosteroids, lithium
Seizures, electric shock
Post-splenectomy
Rebound after neutropenia

Drugs: antipsycotics, antiepileptics,

propylthiouracil (anti-thyroid), gold salts, sulfa
drugs, chemotherapy
Neutropenia Infections
Immune: SLE, Feltys syndrome
Familial/congenital
Endocrine hyperthyroidism, hyperpituitarism
 Rheumatoid arthritis
Feltys syndrome Splenomegaly
neutropenia

Neoplasia
Allergic disorders
Eosinophilia Addisons disease
Collagen Vascular disease
Parasites

Hypersensitivity reactions
Basophilia Chronic myeloproliferative diseases
Thyroid disease

Viral infections
Bacterial infections
Lymphocytosis CLL (chronic lymphocytic leukemia)
lymphomas

immunodeficiencies
immunosuppressive drugs
lymphomas
granulomatous disease, including TB and
lymphocytopenia sarcoidosis
alcoholism
malnutrition
zinc deficiency
 bacterial infections: TB, syphilis, bucellois, SBE,
typhoid!!
Protozoa infections
Rickettsial infectionsincl. rocky mountain
monocytosis spotted fever
Myelodysplastic features
Leukemias
Other malignancies
Inflammatory bowel disease

Neutorphils lack beta2 integrins for surface

adhesion, unable to leave circulation
LAD Peripheral WBC count is ELEVATED because
they cant leave
Recurrent infections with lack of pus

X linked defect in components of NADPH

oxidase complex
Chronic granulomatous disease Recurrent pyrogenic infections with organisms
that are catalase positivedegrades H2O2
Eg staph aureus (has Exotoxin F, TSS)

Autosomal Recessive defects in granule fusion with

plasma membrane
Chediak-Higashi syndrome Defects in leukocyte function, platelet function
Deaths in early childhood

CALM
Corticosteroid use
Alcoholism
Acquired defects in neutrophil function Leukemias
Myelodysplasia
Myeloproliferative syndrome