Heme II review (weeks 1-9)

Anemia

Anemia

decrease in circulating RBCs (impaired production, blood loss, inc destruction)

What are the general symptoms of anemia?

- skin pallor/pale conjunctiva
- dizziness
- SOB
- fast/unusual heartbeat

How does the body respond to anemia?

redistribution (shift to the right), inc cardiac output, inc production

Absolute primary PV

- low EPO
- JAK2 mutation
- thrombocytosis, ruddy complexion, poor O2 delivery, neuro

Absolute secondary PV

- INC EPO
- tissue hypoxia, left shift

What is the difference between appropriate and inappropriate increase in EPO for Polycythemia vera?

appropriate: body makes to much, tissue hypoxia, left shift
inappropriate: fake EPO, tumors, renal, genetic defects

Aplastic anemia

pancytopenia with hypocellular marrow

What are the symptoms associated with aplastic anemia?

bleeding, infections, typical anemia symptoms, iron overload

Lab findings for aplastic anemia

N/N, low WBC plts and retics, ^^ plasma/urine EPO, increased iron storage

Fanconi's anemia

pancytopenia by 8 y/o (congenital defects: short stature, malformed fingers/toes/organs)

Acquired red cell aplasia

no erythropoiesis from infection, thymoma, cytotoxic Ab

Diamond-Blackfan Anemia

congenital red cell aplasia w/ normal WBCs and plts

Anemia of chronic disorders

- 2nd to infection, malignancy, RA or SLE
- Hepcidin (blocks iron release, inc storage)

Anemia of renal insufficiency

- elevation of BUN=severity of iron
- BURR CELLS
- abnormal plt function

Anemia of Liver disease

target cells, acanthocytes, macrocytosis

Anemia of endocrine disease

hypothyroidism and androgen deficiency

Myelophthisic anemia

bone marrow proliferation and proliferation of tumor cells

What makes up a hemoglobin molecule?

4 polypeptide subunits, each w/ a globin chain and a heme

Heme synthesis pathway important steps

rate limiting: ALA synthase
2 ALA > PBG
4 PBG > uroporphyrinogen
Iron into ^ by ferrochelatase

What causes porphyrias to occur?
What are the 2 main symptoms?

block in the heme synthesis due to deficiency in enzymes (photosensitivity and red fluorescence under UV)

Acute porphyrias:

AIP: defect in uroporphyrinogen (build up ALA and PBG)
Coproporphyria
variegate: defect in PPOX (ALA + PBG in urine)

Chronic Porphyrias

congenital/erythropoietic: most severe, defect in uroporph synthetase
acquired: lead intox (blocks ferrochelatase, ALA enzymes)

What are the 2 iron forms?

ferric (3+) and ferrous (2+)

Iron deficiency lab values

- dec ferritin (most sensitive)
- low serum iron
- inc TIBC
- dec sideroblasts

What are the stages of iron deficiency?

1. iron depletion
2. iron deficiency erythropoiesis
3. iron deficiency anemia (micro/hypo)

What symptoms are associated with iron deficiency anemia?

common anemia ones, pica, tongue soreness/ulcers, spoon shaped nails

What are the causes of iron excess?

inc absorption, repeated transfusion, drugs/vitamins

Primary familial hemochromatosis

abnormality of HFE gene (chrom 6) which regulates iron absorption through hepcidin

Sideroblastic anemia

defective use of iron during heme synthesis (M/H, inc serum iron and sat)

Causes of sideroblastic anemia

hereditary: abnormal ALA synthase, pyridoxine-responsive (treat w B6)
acquired: malignancy or drug (isoniazid)

Properties of hemoglobin

1. cooperative binding of O2
2. Bohr effect
3. effect of 2,3 DPG

Hemoglobinopathies

normal rate of production, structure is abnormal

Thalassemias

abnormal rate, normal structure

Sickle Cell Anemia

B6 glu > valine
AAs (no falciparum)
splenic complications, symptoms from occluding small vessels, aplastic crisis

What tests can be used to detect sickle cell?

screen: dithionite (solubility) metabisulfite (slide)
confirm: electrophoresis

Hemoglobin C disease

B6 glu > lysine
AAs
spherocytes, target cells, HGB-C crystals

HGB-D

B21 glu > glutamine
asian indians
spherocytes, target, HGB-C crystals

HGB-E

B26 glu > lysine
oriental asians

Methemoglobin

HGB-M (iron in Hgb ferric state)
cyanosis
methylene blue injections (treatment)

What test is used to detect unstable hemoglobins

heat instability test or isopropanol precipitation test

B0 thalassemia

beta chain synthesis is absent (deleted gene or mRNA is absent)

B+ thalassemia

B chain synthesis is only reduced (defects in transcription and processing of mRNA)

delta beta thalassemia

gene deletions involving both the delta and beta genes

Lepore thalassemia

normal a genes, abnormal delta-beta genes due to fusion

megaloblastic anemia

- vit B12 or folic acid
- macrocytes and ovalocytes
- hypersegmented
- pancytopenia

Hereditary Spherocytosis

mutation in structural proteins, inc autohemolysis test

Hereditary elliptocytosis

abnormal spectrin, inc autohemolysis

Hereditary Pyropoikilocytosis

african americans, marked poikilocytosis and fragments

Hereditary Stomatocytosis

slit-shaped pallor, shortened RBC survival bc less flexible

G6PD deficiency

dec in NADPH and GSH cause oxidative stress, HEINZ bodies, = fluorescence

PK deficiency

dec in ATP production, + fluorescence

Lazy leukocyte syndrome

no response to chemotactic factors

CGD

defective NADPH oxidase, cells can eat but not kill, NTB test

Myeloperoxidase deficiency

no peroxidation

Chediak-Higashi

defective granules, infection, albinism, bleeding

Toxic granulation

in neutrophils, severe infections

Dohle bodies

RNA and free ribosomes, PAS +, infections and scarlet fever

May-Hegglin anomaly

PAS=, myosin heavy chain, genetic

Alder-Reilly Anomaly

genetic, granules in all WBCs, abnormal deposition and storage of mucopolysaccharides

Ehrlichia

lone star tick bite, morulae

Pelger-Huet Anomaly

band, 2 segments, peanut, sunglasses shape

Hereditary hypersegmentation

4 or more lobes in majority of neutrophils

Gaucher's disease

faulty GBA gene, PAS +

Nieman-Pick disease

accumulation of sphingomyelin, PAS =, pick cell

Neutropenia

< 3 X 10^3
dec marrow production, dec survival, INFECTION

Neutrophilia phases

1. early infection migration
2. marrow supply rises
3. recovery (monos inc)
BM exhaustion: failure to fight infection

Leukmoid reaction

left shift, INC LAP

Eosinophilia

allergic disease, parasitic infection, Loeffler's syndrome (sputum)

Basophilia

allergic response, ulcerative colitis, CML or PV

CML

t(9;22), BCR-ABL gene, gleevec/imatinib (tyrosine kinase inhibitor)

PV

erythroid proliferation, INC LAP, dec EPO

PMF

megakaryocyte proliferation, extramedullary hematopoiesis, dacrocytes, dry BM aspirate

ET

hemorrhages, mega proliferation, platelet plugs=neuro, M/H

MDS w/ single lineage dysplasia

< 1% blasts in PB, < 5% in BM

MDS w/ excess blasts

1-5% blasts in blood, 5-20% in BM, fastest to transform to AML

CMML

monocytosis < 20% blasts