hematological disorders
TRANSCRIPT
OCCUPATIONAL HAEMATOLOGICAL DISORDERS
Dr. Dalia Abdallah El-ShafeiLecturer, Community medicine department, Zagazig University
#Haem synthesis
(Pb)
# cell production
(Benzene)
++ leukemia
(IR)
Haemolysis
(As + Naphthalen+ others)
# O2 delivery
(MetHb, SulfHb, COHb)
ScreeningHistory
Physical examination
Blood examination
Bone marrow examination
Other studies
HISTORY
Usually, Non-specific symptoms.
• Anemia.
• Jaundice.
• Pica.
• Infections.
• Thrombocytopenia.
• Drug history.
Detailed work history
PHYSICAL EXAMINATION
Pallor, jaundice, cyanosis.
Abnormal bleeding.
Infections.
Bone tenderness (sternum)
BLOOD EXAMINATION
HB, Hematocrit value
MCV, MCHC, MCH
Peripheral blood smear ( RBCs morphology)
Leucocytes differential count.
Reticulocytes.
BONE MARROW EXAMINATION
Iliac crest or sternum.
• Tumor cells
• Abnormal hematopoietic cells
• Chromosomal studies (proto-
oncogenes- philadelphia chromosome)
OTHER STUDIES
Bleeding disorders (platelet count + PT +
PTT)
Iron stores estimation (serum iron + TIBC +
serum ferritin)
Hemolysis (LDH, Indirect bilirubin).
Rapid cell turnover → ↑ serum Uric acid
INHIBITION OF HB SYNTHESIS
LEAD POISONING
"Lead makes the mind
give way."
ANCIENT AWARENESS
Greek
Dioscerides - 2nd BC
150
10
20
30
40
50
100
Death
EncephalopathyNephropathyFrank Anemia
Colic
Hemoglobin Synthesis
Vitamin D Metabolism
Encephalopathy
Frank Anemia
Decreased Longevity
Hemoglobin Synthesis
Nephropathy
Peripheral NeuropathiesInfertility (MEN)
Systolic Blood Pressure (MEN)
Hearing Acuity
Erythrocyte Protoporphyrin(Women)
Hypertension (?)
Nerve Conduction Velocity
Erythrocyte Protoporphyrin
Vitamin D Metabolism(?)
DEVELOPMENTAL TOXICITY
IQHEARINGGROWTH
Transplacental Transfer
Blood Lead(ug Pb/dl)
- Low birth weight- Miscarriages, Stillbirth- Premature birth
CHILDREN ADULTS
#HB synthesis#Globinsynthesis
#Pyrimidine 5”-nucleotidase
enz.
Iron accumulation
Basic Defects
ANEMIA AND LEAD TOXICITY (90%)
Normochromichypochromic,
normocyticmicrocytic
Reduced RBCs survival time
Compensatory reticulocytes production
reticulocytosis
Basophilic stippling (70%)
↑ urinary excretion of ALA +
Coproporpherine III +Uroporphyrin +lead
MICROCYTIC ANEMIA
WITH BASOPHILIC STIPPLING
LEAD PROVOCATION TEST
CaEDTA infusion “1g in 500ml 5%dextrose”
over 6 hs → 24-hs urinary lead.
• Normally < 0.5 mg
• Lead toxicity → ≥ 1 mg
INHIBITION OF CELL PRODUCTION
BENZENE POISONING
DESCRIPTION
Colorless or light yellow liquid
Sweet odor (Conc. Below threshold of smell associated with toxicity)
Highly flammable.
Evaporates into the air very quickly. Its vapor is heavier than air and may sink into
low-lying areas.
Glues, Paints,
Furniture wax,
Detergents
Tobacco smoke,
Gas stations, MV
exhaust, Industrial
emissions
HIGH-RISK BENZENE EXPOSURE JOBS
Adhesive production
Aircraft engine & fuel workers
Automotive mechanics
Brake technicians
Chemical plant workers
Engine & turbine workers
Gasoline distribution workers
House painters
Newspaper press workers
Painters
Paper and pulp
Pesticide manufacturing
Pipefitters
Printers & print shop
Refinery workers
Shoe / leather workers
Solvent workers
Synthetic rubber
Tankermen
Truck drivers
MECHANISM OF TOXICITY
Benzen induces pancytopenia by
disrupting cell production from the
pluripotent stem-cell stage to the
functional stage.
There is good evidence that benzene is
cancerogenic.
GENETIC SUSCEPTIBILITY
Genetic variations of Myeloperoxidase
& NADPH quinine oxidoreductase
Euphoria,
Dizziness,
Headache,
Blurring of vision,
Mucous membrane irritation,
Tremor,
Chest tightness,
Respiratory depression,
Cardiac arrhythmia,
Coma
Convulsion.
Direct skin contact → Marked irritation due to defeating action of the solvent.
ACUTE POISONING
# BM cell proliferation:
Anemia (including aplastic anemia), leucopenia, thrombocytopenia, pancytopenia;
CHRONIC EXPOSURE
Mutagenic effect:
Leukemia (particularly of the myelomonocytictype),
Chromosomal abnormalities
A dry, scaly dermatitis may developed onprolonged or repeated skin exposure to liquidbenzene.
BM ASPIRATION
Hypocellular with lymphocyte predominance
+ Immature cells
No fibrosis
Acute myelogenous leukemias (AML)
Myeloma, CLL, CML
MANAGEMENT
Blood transfusion
Neutrophil transfusion
Stem-cell transplantation from HLA identical
siblings:
Sever aplastic anemia
Young pt.
Need immunosuppression
OTHER AGENTS # BM GROWTH
Aplastic anemia
Insecticides
“lindane”
Solvents
“glues, kerosesn, ”TNT, CCL4
IR
INDUCTION OF LEUKEMIA
IONIZING RADIATION
TYPES OR PRODUCTS OF IONIZING
RADIATION
or X-rayNeutron
COSMIC RADIATION
2ry ionizing effects
Indirect ionization
Direct ionization
• Neutrons
• x, rays
•α,
• Cosmic rays
Radiation interacting with cell molecules
IONIZING RADIATION AT THE CELLULAR
LEVEL
Causes breaks in one or
both DNA strands or;
Causes Free Radical
formation
OH.(hydroxyl radical)
H.
Radiation Damage
water molecule
-ray
2 OH. H2O2
What happens
when the water
molecule is
struck by the
gamma ray?
PENETRATION ABILITIES OF DIFFERENT
TYPES OF RADIATION
Alpha ParticlesStopped by a sheet of paper
Beta ParticlesStopped by a layer of clothing
or less than an inch of a substance
(e.g. plastic)
Gamma RaysStopped by inches to feet of concrete
or less than an inch of lead
Radiation
Source
NeutronsStopped by a few feet of concrete::
1:100:10,000
DOSE RESPONSE TISSUE
Very High White blood cells (bone marrow)
Intestinal epithelium
Reproductive cells
High Optic lens epithelium
Esophageal epithelium
Mucous membranes
Medium Brain – Glial cells
Lung, kidney, liver, thyroid, pancreatic
epithelium
Low Mature red blood cells
Muscle cells
Mature bone and cartilage
MYELODYSPLASTIC SYNDROME
Cytomenia + remarkably cellular
BMDyserthropoiesis
Rigid sideroblastsVariable no. of
blasts (<leukemia)
MDS
“pre-leukemic”
ACUTE RADIATION SYNDROME
(A SPECTRUM OF DISEASE)
ACUTE HEALTH EFFECTS
Changes in the blood cells
Vascular changes
Skin irritation
Gastrointestinal effects
Radiation sickness:
• Diarrhea
• Nausea
• Vomiting
• High fever
Hair loss
Burns
58
MONITORING INSTRUMENTS
Personal monitoring:
Film badges, bracelet, rings
Pocket dosimeter
Alpha Survey Meter
Detecting Radiation
Beta & Gamma
Survey Meter
LABORATORY FINDING
CML, CLL.
BM →↑ cellularity “ mainly Neutrophils”
Chromosomal analysis:
Philadelphia chromosome
Auer rods.
“King of Poisons, Poison of Kings”
HEMOLYTIC DISEASE
ARSINE POISONING
Industrial processes
Semiconductor manufacturing (gallium arsenide)
Fossil fuels
Wood treated with arsenic preservatives
Metallurgy
Smelting (copper, zinc, lead) & refining of metals & ores
Glass manufacturing
Commercial products
Wood preservatives
Pesticides
Herbicides
Fungicides
Food
Seafood and fish
Others
Antiparasitic drugs
Folk remedies
OTHER HEMOLYTIC DISEASES
MARCH HEMOGLOBINURIA “FOOTSTRIKE
HEMOLYSIS” “RUNNER’S ANEMIA”
Repeated force (trauma) to the foot cause
the breakdown of RBCs in blood vessels.
CAUSES
Hard surfaces, long distances, Worn out
shoes, Inherited RBCs problem
(hereditary spherocytosis).
IMMUNE MEDIATED HEMOLYTIC ANEMIA
AGENTS INTERFERE WITH
O2 DELIVERY
METHEMOHLOBINEMIA
SULFHEMOGLOBINEMIA
CARBOB MONOXIDE