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