Immunity / Haematology Flashcards
List two different classifications of the various anaemias.
- Classification by mechanism:
-
Blood loss
- Acute
- Chronic
-
Increased RBC destruction (haemolysis)
- Inherited genetic defects
- Red cell membrane disorders - hereditary spherocytosis
- Enzyme deficiencies - G6PD def’y, pyruvate, glutathione pathway def’ys
- Hb abnormalities - Thalassemias, Sickle Cell
- Acquired genetic defects - Paroxysmal nocturnal haemoglobinuria
- Antibody mediated destruction - Haemolytic disease of the newborn (Rh disease), transfusionreactions
- Mechanical trauma - Vessels: DIC, Heart: Valvular disease, Repetitive trauma: runners
- Infections of RBCs: Malaria
- Toxic/chemical injury: Snake venom, Pb poisoning
- Membrane lipid abnormalities - Severe hepatocellular disease
- Sequesteration - Hypersplenism
- Inherited genetic defects
-
Decreased RBC prod’n
- Inherited - eg Thalassemias
- Nutritional deficiencies - eg B12 and folate, Fe def’y
- EPO def’y - eg renal failure, anaemia of chronic disease
- Immune mediated - aplastic anaemia
- Inflam’n mediated - Anaemia of chronic disease
- Neoplastic: Primary: Acute leukaemia, Malignancy: space occupying marrow lesions
- Infection: Parvovirus B19
- Classification by morphology:
- Size: Micro, macro normocytic
- Colour: Hypo, normochromic
- Shape
Discuss the intra and extra vascular hemolytic anaemias. What are the principal clinical findings in each type?
Intravascular haemolysis:
Clinical findings:
- Anaemia
- Hemoglobinaemia
- Haemoglobinuria
- Heamosiderinuria
- Jaundice
NB released Hb binds to haptoglobin and phagocytosed (complexes are catabolised resulting in inc’d bilirubin and jaundice) but stores of haptoglobin are depleted -> free Hb inc’s and some oxidised to methaemoglobin. Both filtered in kidneys, some resorbed but some not -> brown urine.
Causes:
- Complement fixation - DIC
- Trauma - cardiac valves, runners
- Toxic - Pb poisoning, clostridial sepsis, malaria
**Extravascular haemolysis: **
Clinical findings:
- Anaemia
- Splenomegaly
- Jaundice
NB: RBCs are recognised by phagocytes in the spleen and prematurely broken down.
Less deformable RBCs (eg heridatary spherocytosis, G6PD def’y, Sickle Cell Disease, Thalassaemias)
Discuss the pathogenesis of pernicious anaemia.
Autoimmune destruction (thought to be a autoreactive T-cell response) of parietal cells in the gastric mucosa results in reduced or absent production of intrinsic factor. Intrinsic factor binds with B12 in the duodenum and this complex is endocytosed by mucosa in the ileum.
Vitamin B12, or cobalamin, is a water soluble vitamin necessary for the formation of Hb and for normal function of the nervous system.
What are the general causes of iron deficiency anaemia. What type of anaemia does this process lead to?
- Insufficient dietary intake
- Impaired absorption
- Increased demand
- Chronic blood loss
Fe def’y anaemia results in a microcytic, hypochromic anaemia.
NB: Only 10-15% of dietary Fe is absorbed.
List the major causes of aplastic anaemia.
Acquired
- Idiopathic (60%)
- Acquired stem cell defects
- Immune mediated
- Idiosyncratic
- Chloramphenicol
- Organic arsnenicals (pesticide)
- Carbamazapine
- Penicillamine
- Phenytoin
- Gold salts
- Chemical agents
- Benzene
- Chloramphenicol
- Inorganic arsenicals
- Alklating chemotherapeutic agents (cyclophosphamide)
- Antimetabolites
- Physical agents
- Whole-body irradiation
- Viral infections
- CMV
- EBV
- Varicella
- Hepatitis (? virus)
Inherited
- Fanconi anaemia
- Telomerase defects
What is the enzyme that regulates Fe absorption in the GIT? How does it work?
Hepcidin is a molecule produced by the liver which reduces absorption of iron from the enterocyte into the blood. Hepcidin levels are directly proportionate to serum Fe levels - ie high Fe levels -> inc’d hepcidin levels -> inc’d inhibition of Fe absorption into the blood. Fe trapped in the enterocyte is then sloughed away when the cell dies.
What are the categories of the causes of aplastic anaemia?
Inherited
Acquired
- Idiopathic
- Idiosyncratic
- Physical
- Chemical
- Viral
List the general categories of causes of thrombocytopaenia.
- Decreased production
- Decreased survivial
- Sequestration
- Dilution
List the general categories of causes of thrombocytopaenia.
Decreased platelet production:
- Selective impairment of platelet prod’n:
- Drug-induced: ETOH, thiazides, diuretics, cytotoxic drugs
- Infections: measles, HIV
- Nutritional def’ys:
- B12, folate
- Bone marrow failure:
- Aplastic anaemia
- BMT
- Ineffective haematopoesis
- Myelodysplastic syndromes
Decreased platelet survivial:
- Immunologic destruction:
- Primary autoimmune:
- Chronic Immune Thrombocytopaenic Purpura
- Acute Immune Thrombocytopaenic Purpura
- Secondary autoimmune:
- SLE, B-cell lymphoid neosplasms
- Alloimmune:
- Blood transfusion, neonatal
- Drug-induced
- Quinine
- Heparin
- Sulphur compounds
- Infections:
- HIV
- Infectious mononucleosis (transient)
- Dengue Fever
- Non-immunologic destruction
- DIC
- Thrombotic microangiopathies
- Giant haemangiomas
- Primary autoimmune:
Sequestration:
- Hypersplenism
Dilution:
- Transfusion
List the causes of DIC.
Solid tumors and hematologic malignancies (particularly acute promyelocytic leukemia)
Obstetric complications: abruptio placentae, pre-eclampsia
or eclampsia, amniotic fluid embolism, retained intrauterine fetal demise, septic abortion
Massive tissue injury:
severe trauma, burns, hyperthermia, rhabdomyoloysis, extensive surgery
Sepsis or severe infection of any kind (virtually infections by any microorganism can cause DIC, though bacterial infections are the most common): bacterial (Gram-negative and Gram-positive sepsis), viral, fungal, or protozoan infections
Transfusion reactions (i.e., ABO incompatibility hemolytic reactions)
Severe allergic or toxic reactions (i.e. snake or viper venom)
Giant hemangiomas (Kasabach-Merritt syndrome)
Large aortic aneurysms
Draw the pathophysiology of DIC.
What are the two primary triggers for the clotting cascade?
- Release of Tissue Factor - tissue destruction, endothelium damage, sepsis
- Exposure of platelets to endothelial collagen
List the factors involved in:
- The intrinsic pathway
- The extrinsic pathway
- The common pathway
- XII, XI, IX, VIII
- VII
- X, V, II, I
What is another name for:
- Factor II and IIa
- Factor I and Ia
- Prothrombin and thrombin
- Fibrinogen and fibrin
List the causes of neutropenia.
Decreased production:
- aplastic anemia
- arsenic poisoning
- cancer, particularly blood cancers
- certain medications
- hereditary disorders (e.g. congenital neutropenia, cyclic neutropenia)
- radiation
- Vitamin B12, folate or copper deficiency
Increased destruction:
- autoimmune neutropenia
- chemotherapy treatments
Marginalisation and sequestration:
- Hemodialysis
Medications:
- Flecainide (class 1C cardiac antiarrhythmic)
- Phenytoin
- Indomethacin
- Propylthiouracil
- Carbimazole
- Chlorpromazine
- Trimethoprim/sulfamethoxazole (cotrimoxazole)
- Clozapine
- Ticlodipine