Lecture 11 - Toxicants Targeting Blood And Immune System Flashcards
Blood
- plasma 55%
- formed elements 45% including rbcs (99%), wbcs
- –> wbcs include neutrophils, eosinophils, basophils, monocytes, lymphicytre
Blood is 8% body weight
Women 4-5
Men 5-7
Types of Blood Cells
-erthyroytes: provides oxygen to body
Eosinophils: phagocytize, invovled in allergic rxns
Monocytes: make macrophages, phagocytize
Neutrophil: first line of defense, phagocytosis and inflammation
Basophils: allergies and inflammation (like eosinophils; allergies)
Lymphocytes: B&T cells (lymph nodes).
Sites of hematopoiesis
Fetus: yolk sac
Newborn: liver and spleen
Chidlren: bones
Adults: axial skeleton
Hematopoesis
Erthirblasts –> RBCs
Monoblasta –> monocytes (agranular)
Megakaryotes –> platelets thrombocytes
Myeloblasts –> granular leukocytes which are base, eosinophils, neutro
Leukemia and Benzene
Benzene may be responsible for immature differentiation of immature myeloid stem cells in ACUTE myelegounus leukemia due to formation of reactive intermediates
- -> increase ROS
- -> decrease glutathione
- -> incrae dna damage
Hematotoxicty
Primary: >=1 compartment is directly affected, commonly due to xdenobitoic
Secodnary: injuries cause damage or systemic disturbance cause indirect blood toxicity
Anemia groups
- Blood loss
- Decreased or faulty production
- Increased destruction
Iron-defieciency anemia
Need to incorporate iron into the ring - if not, get iron defiance nemia (det or bloodloss)
- iron defiance anemia leads to small, pale RBCs
- cox inhibitors/anything inducing git bleeding can causeiron defieicn anemia
Sideroblastic anemia
-sideroblastic anemia=defects in synthesis of polyphonic ring; the incorporation of iron into the ring is targeted in sideroblastic anemia
“”"”Ringed sideroblastic” pathology (blue pernculea r granules due to stain)
-iron accumulates within cells, bc canot be used in Hb
Sideroblastic anemia malfunction to incporate iron in hemoglobin an be caused by:
Aminolrulbinci acid synthase (RLS)
Pyridoxical-5-phosphate (VB6) which is a co-factor for aminolrvulonic acid synthase
ALAD-alaumi–dehydrates
Megaloblastic Anemia
-rbcs are larger than normal but count is low
Causes:
-v12 (cobalamin) or vb9 (folate) deficiencies
-most often drug induced rather han dietary defieicnt; caused by impairment of absorption (intrinsic factor necessary for b12 absorption)
NITE: ETHANOL CAN DECREASE INTRSINCI FACTO ABSORPTION LEADING TO MEGOBLASTIC ANEMIA
Other causes:
Targeting thymidylate synthase, dihydrofolate reductase
Aplastic anemia
Inability of stem cells to generate mature RBCs
Decrease in# cells
Hemolytic Anemia
-lysis of RBCs before end of normal life cycle
Immune vs non-immune:
Immune=xenobiotic coats the rbc and antibodies form against i (ex: penicillin)
Non-immune: due to an ncrease in ROS, associated with G6P defieicny (WHICH PROVIDES NADPH, WHICH IS NEEDED FOR GLUATTHIONE)
THIS non-immune hemolytic anemia can be induced by fauvism favaismmmmm, x-linked recessive
Pathology histology of hemolytic anemia: “bite cells” or Heinz bodies
Methemoglobinemia
-fe2+ –> fe3+ fERRIc due to ROS, causing methemoglobin,mcannot carry oxygen
As [c] increases, get cyanosis
~70%=death
High levels of sodium nitrates increase methemoglobin (hot dogs r bad) also in ground water
Cytochromes b5 reductase, also methamglobin reductae (less)
Platelets
Cystosis=higher
Cytopenia=lower production or increased destruction
These can be due to drugs or chemo or penicillin
Dugs can mess up platelets; cleaving fibrinogen –> fibrin
Platelet formation via vitamin K, inhibit Vk=inhibit cutting faxctor = warfarin
Neutrophils
WBC Granular First line of defense 40-60% of wbc are neutrophil Multilobe nucleus phagocytosis, Neutropenia: low levels of neutrophils, increased infection
