Monday 17 November 2008

Heading for London

Sorry about lack of posting in last week or so - have been 3rd on-call in theatre with some pretty hectic shifts - all good experience (met someone with CREST syndrome yesterday - anyone remember that from medical finals?? As with all syndromes, potentially difficult airway which thankfully for us turned out to be relatively straightforward). Anyway, I'm digressing so back to the point.

I passed the written paper (much relief!) - congratulations to everyone else who did. So, we have three weeks of intense viva practice ahead. Make sure you pester all of your colleagues at work to viva you - try and focus in on their specialist interests as they will have more to offer. There are usually a few secret physics and statistics whizzkids hiding in each department too!

Today, I thought I would mention investigations. I got slightly caught out during my last clinical viva when asked about FBC and the various indices, and about sickledex testing, so it's worth having a quick look at a few basic investigations.

FBC
-RBC Count: the number of red cells in the blood.
-Hb: concentration of HB protein in blood. Normal values: 12 to 18 g/dL of blood but are influenced by the age, sex and ethnic origin in the person.
-PCV (Hct): % of total blood volume occupied by red cells. The haematocrit is the proportion, by volume, of the blood that consists of red blood cells post-centrifugation.
-MCV: mean volume of red cells. Normal range 82-98 fl
-MCH: mean amount of Hb in red cells. Normal range 26-34 pg
-MCHC: mean concentration of Hb in red cells. Normal range 31-37 g/dl
-RDW: red cell distribution width (measure of variation of RBC population). Normal range 11.5-14.5%



Haemostasis/Clotting
-APTT: activated partial thromboplastin time measures efficacy of contact activation (formerly intrinsic) and common coagulation pathways. Monitors effective heparin treatment.

-PT: prothrombin time determines clotting tendencies of blood (formerly extrinsic pathway measurement). Trends useful in measuring efficacy of warfarin treatment & progress of liver damage. INR derived from PT: ratio of pt's PT to control sample (raised to power of specific sensitivity index).

-Platelet function: bleeding time & thromboelastography (a measure of clot formation speed and clot strength)

Sicle Cell Testing
-Sickledex (or sickle solubility testing): a blood sample is added to a reducing solution (e.g. sodium dithionite). HbS will give a turbid appearance whilst HbA will give a clear solution. Remember that this test does not distinguish between HbSA and HbSS, merely the presence of the sickle gene.

-Hb electrophoresis: different types of Hb move at different speeds along the gel. Can confirm with high-performance liquid chromatography.

Biochemistry
-HbA1c: Glycosylated Hb identifies average blood glucose conc over period of time. Measured by chromatography or immunoassay. The International Diabetes Federation and American College of Endocrinology recommend HbA1c values below 6.5% (Normal ref range: 4-5.9%).

-Urea: product of amino acid breakdown to ammonia which is produced in the urea cycle. It is filtered freely at the glomerulus and approx. half is reabsorbed in the PCT. Responsible for the majority of daily nitrogen excretion.

-Creatinine: Formed constantly from phosphorylcreatine in skeletal muscle. It is freely filtered by the glomerulus, but also actively secreted by the renal tubules in very small amounts such that creatinine clearance overestimates actual GFR by 10-20%. However, the values agree quite well with the GFR values measured with inulin because the value for plasma creatinine concentration is also high as a result of nonspecific substances, cancelling out the error.

-Troponins: Trop I, C, T are three protein sub-units of larger troponin complex. Trop C binds to Ca2+ leading to conformational change in Trop I. Trop T binds other troponin components to tropomyosin forming a complex. Trop I binds to actin to hold the previous complex in place by inhibiting ATP activity. Trop I & T are not normally found in plasma, but raised levels are v.sensitive/specific indicators of cardiac damage and differentiate between unstable angina & MI. Troponin C is not used to measure myocardial damage as this isoform is shared with skeletal muscle, rendering it non-specific. Levels are measured by immunoassay methods.