Yr 2 Haem

Front 1

Erythrocyte origin + life span?

Back 1

myeloid stem cell/precursor -> proerythroblast -> erythroblasts -> erythrocytes;life-span 120 days

Front 2

Erythropoietin synthesis occurs in?

Back 2

juxtatubular interstitial cells in kidneys in response to hypoxia

Front 3

Neutrophil origin?

Back 3

myeloblast -> promyelocyte-> myelocyte-> band form-> neutrophil

Front 4

Platelet: origin, function & lifespan?

Back 4

megakaryocytes; 10 days in circulation; role in 1˚ haemostasis;contribute to phospholipid -> promotes blood coagulation.

Front 5

MCH?

Back 5

MCH = Hb÷RBC

MCH = absolute Hb amount in individual red cell, tends to be parallel toMCV in macro/microcytic anaemia

Front 6

MCHC?

Back 6

MCHC = Hb÷Hct

MCHC = concentration of Hb incell, related to shape, measuredelectronically with light scattering.

Front 7

Anisocytosis is...?

Back 7

abnormal size variation in RBCs

Front 8

Poikilocytosis is...?

Back 8

abnormal SHAPE of RBCs;

target cells (obstructive jaundice, liver disease)

elliptocytes (hereditary elliptocytosis + irondeficiency),

sickle cells(HbS polymerisation;genetic),

schistocytes (fragements)

Front 9

Atypical lymphocytes are typical of?

Back 9

Glandular fever/infectious mononucleosis

*Glandular fever: EBV (Herpes) infection of B-cells via CD21 receptor + infected B cell proliferates & shows EBV antigens; therefore T-cell mediated response & acute infection resolved but life-long sub-clinical infection

Front 10

Left shift =?

Back 10

increase in non-segmentedneutrophils or neutrophil precursorsin blood

Front 11

Toxic granulation=?

Back 11

heavy neutrophil granulation due to infection, inflammation + tissue necrosis; also in normalpregnancy

Front 12

Hypersegmented neutrophil due to lack of?

Back 12

lack of vit B12/folic acid

Front 13

Rouleaux =

Howell-Jolly body=

Heinz bodies=

Back 13

Rouleaux = RBC stacks (alterations in PP)

Howell-Jolly body= nuclear remnant in RBC (due to lack of splenic function)

Heinz bodies= denatured haemoglobin; removed by spleen

Front 14

Haemostatic plug formation steps?

Back 14

vessel constriction (initialresponse, more important in small vessels, localcontractile response)

unstable plug (two steps = plateletadhesion to damaged wall + plateletaggregation)

plug stabilisation with fibrin(unstable plug breaks down on its own, fibrin network formation stabilises)

fibrinolysis (plug broken down, clot dissolution, vessel repair).

Front 15

Prostaglandin metabolism?

Back 15

Products= prostacyclin in endothelial cells & Thromboxane A2 in platelets

Front 16

Aspirin is an inhibitor of which enzyme?

Back 16

COX inhibitor

Front 17

2 clotting cascade pathways?

Back 17

INTRSINIC + EXTRINSIC (briefly describe)

Front 18

Fibrinolysis initiated by which 2 proteins?

Back 18

Plasminogen (pp- plasma protein) & tissue plasminogen activator (tPA)

Plasminogen -> plasmin by tPA ->breaks down clot

Front 19

What is APTT & what is it used for?

Back 19

Activated Partial Thromboplastin Time; detects intrinsic + common pathways abnormalities & measures clotting time; used to monitor heparin treatment

(*-PT used to monitor warfarin treatment + extrinsic pathway abnormalities)

Front 20

MOA of Warfarin (anticoagulant) + indication?

Back 20

Warfarin inhibits vit K (inhibits assembly of active complexes on plateletsurface + reduces thrombin production)so stopgamma carboxylation by vit K Epoxide Reductase (stops clottingfactors binding to platelet surface)

Used for LONG-TERM anticoagulant therapy (after treated for venous thrombosis + atrialfibrillation)

Front 21

MOA of Heparin (anticoagulant) + indication?

Back 21

Potentiates action of anti-thrombin by binding to it (so ↑f10a + thrombininhibition) & changes reactive loopposition

Used for immediate anticoagulation in venousthrombosis + pulmonary embolism

* Has TWO forms = low molecular weight heparin (favoursf10a inhibition) + standard/unfractionatedheparin (inhibits both).

Front 22

MOA & examples of anti platelets + indications?

Back 22

ADP receptor antagonists +COX1 antagonists: clopidogrel, abciximab (antibody – gp2b/3a antagonist), tirofiban (small molecule – gp2b/3a antagonist)

Used in CVD; combos for angioplasty, stents

Front 23

Functions of:

Gp1a

Gp1b

Gp2b/3a?

(on platelets)

Back 23

Gp1a= allows platelets to bind DIRECTLY to exposed collagen

Gp1b= VWF binds to collagen then platelets bind to VWF through Gp1b (INDIRECT)

LACK= Bernard Soulier Syndrome

Gp2b/3a=(on activated platelets) fibrinogen binds

Lack=Glanzann’s Thrombasthenia

Front 24

Function of alpha granules on platelets?

Back 24

alpha granules – storage for proteins (factor 5, VWF), released when platelet activated

(Also thrombin R and Gp on surface of platelets)

Front 25

Define Anaemia & what are 3 types (+ causes of each)?

Back 25

Low Haemoglobin concentration in a given volume of blood

Microcytic (usually hypochromic,common causes are haem synthesis defect (irondeficiency, chronic disease) + globinsynthesis defect/thalassaemia (α or β chain synthesisdefects)) --> leads to reticulocytosis

Normocytic

Macrocytic (Abnormal HAEMOPOIESIS – failure to divide properly due to lack of B12 of folic acid, dugs that interfere with DNA synthesis:Chemotherapy, Azathioprine, liver disease/ethanol toxicity, Haemolytic anaemia, Major blood loss)

Front 26

Mechanisms of normocytic normochromic anaemia + causes?

Back 26

Mechanisms:

Reduced production of Red cells by thebone marrow

Loss of blood – haemorrhage

Reduced survival of RBC’s in thecirculation – haemolytic

Pooling of RBC’s in an enlarged spleen

Causes: Peptic ulcers, oesophageal varices,trauma, hypersplenism (portal cirrhosis)

Failure production of RBC’s: Early stages of iron deficiency, renal failure, bone marrow failure/suppression, Bone marrow infiltration.

Front 27

Define Haemolytic anaemia + its effects on vasc system? (also what do you expect to find?)

Back 27

Anaemia resulting from shortened survival of red blood cells in the circulation (can be inherited- sickle cell/G6PD def/hereditary spherocytosis or accquired- autoimmune, drugs)

Intravascular:very acute damage

Extravascular:defective red cells removed by the spleen

Normochromic,normocytic/macrocytic, morphologically abnormal RBC’s, Evidence of increasedred cell breakdown, evidence of increased bone marrow activity

Front 28

What is hereditary spherocytosis & its treatments?

Back 28

Loss of cell memb w/o loss of cytoplasm. – Hereditary intrinsic defect

Cells increased MCHC Redcells become larger, rounder, and less flexible. Can’t move out of spleensinusoids so prematurely destroyed by spleen – extravascular haemolysis

Leads topolychromasia and Reticulocytosis

TREATMENT: Splenectomy + vitamins (folic acid, B12 and iron)

Front 29

Describe iron absorption in gut + what is the role of hepicidin?

Back 29

Movesfrom gut lumen into cell via Haem Carrier Protein/HCP-1 (Heme) or DMT-1 (Fe2+)

Once incell moved to BM where enters blood via ferroportin

Once inplasma binds to Transferrin

Hepcidin= Keyregulator of the entry of iron into the circulation

If hepcidin is high – indicates high iron in blood

Front 30

Role of ferritin & its levels in iron deficiency & chronic disease?

Back 30

Acute reactive protein + bind to iron and stores it (so indicates levels of iron stores in body)

Irondeficiency – Low

Chronicdisease – High (BC IT IS ACUTE REACTIVE PROTEIN)

(* Transferrin -carrier protein for iron in the blood- levels:

Irondeficiency – Increases

Chronicdisease – Normal/Low)

Front 31

Why is ABO compatibilty important in blood transfusions?

Back 31

ABO incompatible transfusion --> fatal antibody-antigen interaction ---> agglutination then, cytokinestorm/lysis/cardiovascular collapse/death

Front 32

Why is it dangerous when RhD–ve mother has an RhD+ve baby?

Back 32

SENSITISATION: RhD negative CAN make anti-D antibodies (IgG) AFTER exposed to D antigen – exposed by transfusion or inpregnancy (RhD+ foetus).

Anti-D ABs can cross placenta --> foetal RBChaemolysis --> hydrops fetalis --> death

Front 33

FFP (what is it + how it is produced/used)?

Back 33

FFP = Fresh frozen plasma

Stored at -30˚C (frozen with6hrs, preserves coagulation factors + separated into cryoprecipitate + supernatant); 2yrshelf life; thawed at room temp.before use (proteins ‘cook’ at high temp.), use within an hour (coagulation factors degenerate)

Front 34

Platelets (how is it stored + matched)?

Back 34

Stored at room temp. (22˚C), constantly agitated (preventsaggregation)

5 day shelf life(risk bacterial infection); no need tocross-match but needs same ABO group (plateletshave low ABO levels)

ONE pool from 4 donors is enough for 1 dose.

Front 35

RBCs (how is it stored + used)?

Back 35

packed cells (plasmaremoved); stored in 4˚ for 5 weeks

inefficient to freeze blood – loseRBCs when thawed

Front 36

When is O2 dissociation curve shifted to the right?

Back 36

By factors that stabilise deoxyHb(decrease affinity, e.g. H+ +2,3-DPG + CO2 = BohrEffect) – so need higher [O2] for binding

NB: As more O2 binds, Hb switches to relaxed form, can accommodate more O­2!!

Front 37

Sicke Cell Anaemia (genetic cause, complications and effects)

Back 37

Point mutation at codon 6 so valine is substituted for glutamic acid --> HbAS (2 normal alpha chains and 2 variant beta chains)

Complications: HbS causes formation of tactoid fibres that cause deoxyHb to form intratetrameric contact to form long polymers in the RBC, damaging it and distorting its shape.

Effects: SICKLE CELL ONLY LASTS 20 days + no hypoxia as HbS readily gives up O2 at respiring tissues- lower affinity- so ANAEMIA); Acute chest syndrome; Pulmonary hypertension (free Hb depletes NO so vasoconstriction); asymptomatic and normal blood count

Front 38

What is used to distinguish between alpha and beta thalassaemia?

Back 38

Increased HbA2 levels in beta thalassaemia

(found by electrophoresis)

Front 39

What are the iron-containing proteins (+ food)?

Back 39

Hb (biggest store; Fe2+ at centre), ribonucleotide reductase, myoglobin, cox, succinate dehydrogenase,cytochrome a/b/c, cytochrome p450, catalase.

Food = meat, fish, vegetables, whole grain cereal, chocolate

(* NB: Fe3+/Ferric iron cannot be absorbed- Tea converts Fe2+ to Fe3+ WHEREAS Orange juice increases Fe2+ absorbing ability)

Front 40

Why are B12 and folate vital?

Back 40

Both needed for the synthesis of deoxythymidine(dTMP), which is a crucial building block in DNA synthesis.

Front 41

Describe B12 absorption

Back 41

B12 binds to R protein (transcobalamin 1)

Gastric parietal cells secrete Intrinsic factor

B12 enters duodenum where it is displaced bypancreatic enzymes

Free it binds to intrinsic factor

In terminal ileum B12-intrinsic factor complexenters via receptor into cells.

Circulation B12 binds to Transcobalamin 2 makingit active B12

Front 42

B12 deficiency tests?

Back 42

Neurologicalexamination, serum B12 level, plasma homocysteine (high in both B12 and Folatedeficiency), Serum methyl malonic acid levels (not freely available),holotranscobalamin levels (active B12)

+ Schilling test (not used anymore)

Front 43

Clinical features of a patient with a B12 and folic acid deficiency?

("JAAWS G!!")

Back 43

Jaundice: Ineffective erythropoiesis

Anaemia: macrocytic, megaloblastic – SOB, weak,fatigue

Angular Cheilosis: soreness in the corner ofyour mouth

Weight loss + change in bowel habit

Sterility

Glossitis: red, raw tongue, painful

Front 44

Causes of B12 deficiency + consequences + treatment?

Back 44

Causes: Diet , Malabsorption- Crohns, Coeliac, Pernicious anaemia

Consequences: Macrocyticand megaloblastic anaemia – reversible with treatment, Neurologicalproblems due to demyelination, Subacutedegeneration of the spinal cord -Cognitiveimpairment, Opticatrophy, Macrocytosis

Treatment: Injections of B12, 1000 ug, 3 times a week for2 weeks. Thereafter every 3 months

Front 45

Vit B12 is co-factor for methionine synthase for...?

Back 45

homocysteine --> methionine conversion – reaction releases methyl groups --> methylate DNA (crucial for DNA synth)

(NB: homocysteine = homologue of the amino acid cytosine, convertedto methionine by methionine synthetase and vitamin B12. High levels of it associated with atherosclerosis and premature vasc disease)

Front 46

Prenicious anaemia (causes + consequences)

Back 46

= Lack ofintrinsic factor (NEEDED FOR B 12 ABSORPTION)

Causes: Autoimmune atrophic gastritis

Patientsmay have intrinsic factor antibodies (20-40%) or parietal cell antibodies(80-90%)

Consequences: macrocytic, megaloblastic anaemia, neurological damage.

Front 47

Describe folate absorption + reasons for malabsorption

Back 47

folic acid (folate polyglutamates)hydrolysed (acid pH) --> monoglutamates; folates absorbed as pteroglutamates --> methylated in luminal cells --> tetrahydrofolates

Malabsorption due to: Coeliac disease (gliadin sensitivity --> subtotal villousatrophy + crypt hyperplasia in duodenum; anti-glandin/transglutaminase antibodies/duodenal biopsy used to diagnose), Surgeryor IBS, Drugs (colestyramine, sulfasalazine, methotrexate,anticonvulsants, alcohol)

Front 48

Consequences of folate deficiency + how is it diagnosed?

Back 48

Megaloblasticanaemia, Neural tube defects – spina bifida andanencephaly, increased risk of venous thromboembolism

Fullblood count, Blood film, Blood folate level, Serumfolate: diurnal variation and affected by recent changes in diet, Red cellfolate: b12 deficiency = high serum folate, low red cell folate

Front 49

How does malignant haematopoiesis in chronic myeloid leukaemia?

Back 49

mutation occurs at GM-CFCphase --> increased prolif of myeloid cells

Front 50

Immature WBC (myelocytes + metamyelocytes) in blood film is indicative of...?

Back 50

Acute leukaemia (low Hb + platelets)

(Only mature WBCs in normal infec + granular neutrophils)

Front 51

Causes of neutrophilia?

Back 51

Infection, tissue inflammation, malignant (myeloproliferative disorders, CML), physical stress, corticosteroids

Front 52

Causes of eosinophilia?

Back 52

Parasitic infections, allergic diseases, Hodgkin's Disease (Hodgkin’s Disease – ↑mediastinal mass on chest x-ray, ↑IL5 secretion --> reactive eosinophilia), Malignant chronic eosinophilic leukaemia (PDGFR gusion gene- detected by FISH)

Front 53

Causes of monocytosis?

Back 53

RARE + chronic infec; TB, Brucella, typhoid; viral = CytoMegaloVirus, varicella zoster;sarcoidosis; chronic myelomonocytic leukaemia (MyeloDysplastic Syndrome)

Front 54

Causes of lymphocytosis?

Back 54

If MATURE cells - reactive toinfection(big nucleus, littlecytoplasm); CLL (esp in elderly), oligoclonal expansion (all cells look alike), autoimmune/inflammatory

If IMMATURE cells (larger, big nucleus, see nucleolus) - ALL (acute lymphoblastic leuk); 2*= infection (EBV --> Herpes, CMV, toxoplasma, infectious hepatitis, rubella, herpes), autoimmune disorders, neoplasia, sarcoidosis

Front 55

How to differentiate between polyclonal and monoclonal antibody responses?

Back 55

POLYCLONAL - in resp to infection. 50:50 divide of Ҡ/λ lightchains in antibodies

MONOCLONAL - all B-cells make either Ҡ OR λ only (NOT as a result of infec.)