Hematology 1.

TransFerrin TRR Ferritin Fe 2+

2. Iron assessment a. Transferrin Only thing changes b. Iron c. Saturation d. Ferritin 3. Hereditary spherocytosis Thalassemia G6PD Deficiency

Haemolyitc anemia

4. Iron absorption- Dietary iron is absorbed by duodenal enterocytes then released into the blood vessel as tranferrin or most of the time ferroportin 5. Hereditary haemolytic anemia Membrane Hereditary Spherocytosis HO Hb Metabolism Thalassemia G6PD Deficiency Hamogolbinopathies Pyruvate kinase deficiency

6. Oxygen dissociation curve 7. G6PD Deficiency- X linked, susceptible to oxidative stress, exposed to certain drugs, food 8. ABO a. Stuff on the RbC (A, B,H antigens) b. Stuff in serum (Anti B, Anti A antibodies) c. Rhesus D+ - D antigens 9. Emergency O blood Low amount of anti-A and anti-B a. Group- O packed ( No plasma, can give with AB plasma which has no antibodies) 10. Red cell metabolism- No organelles anaerobic glycolysis, antioxidant function 11. ATP Generation a. NADPH for antioxidant function b. NADH for methaemoglobin reduction c. ATP to maintain membrane cytoskeletal function

12.

IRON

+ PROTOPORPHYRIN
sideroblastic anemia

Iron deficiency, malignancy

Chronic inflammation

HAEM

GLOBIN
Thalassaemia, hbpathies

HAEMOGLOBIN

Anemia 1. Excessive blood loss a. Trauma, menstruation, ulcer, hemophilia, ruptured aneurysm 2. Blood cell destruction(haemolysis) a. Malaria invasion, destruction RBC plasmodium b. Acute haemolytic anemia AIHA, G6PD deficiency, penicillin c. Hereditary Hb- Thalassemia d. HDN- RhD mismatch between baby and mother 3. Impaired blood cell formation a. Nutritional causes iron deficiency b. Renal failure c. Destruction of stem cell/myeloid tissue

Haemolytic anemia o Immune  Autoimmune  Alloimmune  Drugs- Rifampicin, methyldopa, penicillin o Acquired  Autoimmune- SLE, CLL  Cold Ab-Idiopathic, 2ry to infections, IM  Alloimmune- haemolytic transfusions, HDN

So, what happens in G6PD def.? RBCs are exposed to oxidative stress, (because when no G6PD, antioxidant NADPH is not made) - lyk infections, drugs (antimalarias, sulphonamides) Increased G6PD in young rbc (reticulocyte), so less haemolysis

Morphologic classification of anemia (MCV and MCH)

Microcytic Hypochromic Iron deficiency Chronic Dz Thalassaemia Sideroblastic anemia Normocytic normochromic Acute blood loss BM infiltration Chronic Dz SLE<,CRF Macrocytic normochromic Folate deficiency Vit B12 deficiency/ Hypothyroidism Liver pathology/ Alcoholism New Born/high reticulocytes

Tiredness, weakness, short of breath, pallor

y y

Iron storage- parenchymal cells of the liver, Re macrophages (haemosiderin ) or ferritin Iron Regulationo Hypoxia o Erythropoetin regulator  Communicates with the demand of EPO  High capacity iron absorption o Stores regulator  Senses of iron stores  Slow accumulation  Reconditions intestinal uptake Causes of IDA o Malnutrition o Malabsorption (celiac disease) o Increased demand, pregnancy, growing child o Chronic blood loss, menorrhagia, GIT , UT PV bleeding Treatment IDA o Oral iron o Depends on the state of ionization (Fe2+ > Fe3+ ) Diagnostic tests Serum Iron (all low except for thalassemia) TIBC (either high or normal in everything) Transferrin Serum ferritin Iron stores Hb

Anemia of Chronic Dz o Decrease erythropoietin o Erythrophagocytosis (shorter RBC survival) (Uremia with CRF) o Related to renal Fe/folate loss in dialysis, platelet function abnormal, no marrow hyperplasia Treatment o Underlying cause o EPO (for CRC) o Avoid iron supplement for chronic infections and malignancy o Iron will traffic now into RE system, not RBC

Thalassemia    FBP- Hb, MCV Hb electrophoresis (beta) Reticulocyte smear (alpha)

MACROCYTIC NORMOCHROMIC y y y Megaloblastic anemia- Inhibition of DNA synthesis in RBC production High MCV, normal MCH Hypersegmented neutrophils- in b12/folate

B-12 deficiency      B12 (cobalt) involves in methylation of homocystein to methionine which involves in lipid synthesis and myelin formation. Storage- liver, Absorption Intrinsic factor(parietal cells small intestine) Diagnosis- Schichlings test Treatment- IM with folate, hy. Cobalamine Dont give folate alone increases the neurological disorder\

Neoplasm - Single precursor cell

clonal expansion (somatic mutation) monoclonal

Leukemia General, proliferation of blood cells in bone marrow/RE system Lymphoma Only in lymphoid organs, spleen, lymph nodes, bone marrow

Leukemia

Myeloid (In bone marrow and spinal chord, any leukocyte that's not a lymphocyte)

Lymphoid (lymphocytes)

AML

CML

ALL (mostly in childrenimmature lymphocyteslymphoblasts)

CLL

Lymphoma

Hodgkins (only lymphocytes Redd-Sternberg cells)

Non-Hodgkins
(other WBC except lymphocytes)

Burkitts B cell lymphoma (Ig, Class 2 MCCH, CD 19) MYC oncogene Reciprocal transolcation of t(8;14)

Follicular B cell BCL 2 gene blocks apoptosis rate of cell division is low, lympho accumulative

CML- Philadelphia chromosome t (9:22)  BCR-ABL gene fusion  Produces abnormal protein, tyrosine kinase  Treatment- alfa interferon, imatinib  Dasatinib and bone marrow transplant/stem cell o New treatment  Monoclonal antibodies  Bone marrow transplant (CD34+) Non-hodgkins o Painless, enlarged lymph nodes o Fever and night sweats o LOW, LOA o Enlarged spleen o +/- jaundice Hodgkins o Fever (pel-ebstein) o Night sweats, pruritis o LOA, LOW, anorexia o Fatigue, cachexia, alcohol-induced pain (itch)

Extrinsic pathway PT (prolonged if anything wrong with your factor 7) Factor 7 is vitamin k dependant Therefore, vit k deficiency, and also because it is produced in the liver (liver cirrhosis, hepatitis) cz deficiency prolonged PT y y y y INR is important ( patients PT/constant value) diagnose PT time is also used to check liver function Warfarin - Vitamin K antagonist, 3 days to start functioning therefore, combine with heparin, crosses placenta PT- purple colour tube , has citrate (absorb Ca2+), +artificial thromboplastin, Cacl2

Intrinsic Pathway APTT y y y Heparin Normal, Low molecular weight Potentiates Antithrombin 4 (small protein molecule that inactivates several enzymes of the coagulation system, glycoprotein produced by liver) Protamine sulfate (antidote) binds with heparin, to reduce its effect o Used e.g. in heart surgery

TT y y Thrombin time (time taken for fibrinogen fibrin) (needed for platelet aggregation) Prolonged TT, due to fibrinogen deficiency o DIC o Snake bite DVT o Tests D dimer, FDP (both of them fibrinolyse)

Other important stuff Haemophilia A and B (Deficiency in factor 9, bleeding into your joints) vWF disease (Deficiency in factor 8) (no joint/ internal bleeding) y Thrombin causes factor 8 to separate from Vwf Deficiency in platelet (bleeding under skin ecchymoses, patechiae) Splenomegaly ( platelets attracted inside, therefore absent in the circulation) ITP (own Ab attack platelets ( Immune thrombocytic purpura) - children Deficiency in coagulation factors (bleeding into your joints) atrophy of muscles painful joint movement

What happens after a fibrin clot is formed, like in PE, stroke????? Plasminogen is converted into plasmin (by tPA, urokinase, streptokinase - by the damaged endothelial blood vessel) Therefore plasmin lyses the fibrin (thrombolysis)