Clinical chemistry – oxford medicine endometrial biopsy results how long

Laboratory medicine reduces our patients to a few easy-to-handle numbers: this is the discipline’s great attraction—and its greatest danger. The normal range (reference interval) is usually that which includes 95% of a given population (given a normal distribution, see p [link]). If variation is randomly distributed, 2.5% of our results will be ‘too high’, and 2.5% ‘too low’ on an average day, when dealing with apparently normal people. This statistical definition of normality is the simplest. Other definitions may be normative—ie stating what an upper or lower limit should be. The upper end of the reference interval for plasma cholesterol may be given as 6mmol/L because this is what biochemists state to be the desired maximum. 40% of people in some populations will have a plasma cholesterol greater than 6mmol/L and thus may be at increased risk.

The who definition of anaemia in pregnancy is an Hb of 110g/L, which makes 20% of mothers anaemic. This ‘lax’ criterion has the presumed benefit of triggering actions that result in fewer deaths from haemorrhage. So do not just ask ‘What is the normal range?’—also enquire about who set the range, for what population, and for what reason.

Plasma is filtered by the glomeruli, and Na +, K +, H +, and water are reabsorbed from this filtrate under the control of the renin-angiotensin-aldosterone system. Reninis released from the juxtaglomerular apparatus (fig 7.13, p [link]) in response to low renal flow and raised sympathetic tone, and catalyses the conversion of angiotensinogen (a peptide made by the liver) to angiotensin I. This is then converted by angiotensin-converting enzyme ( ace), which is located throughout the vascular tree, to angiotensin II. The latter has several important actions including efferent renal arteriolar constriction (thus ↑perfusion pressure), peripheral vaso-constriction, and stimulation of the adrenal cortex to produce aldosterone, which activates the Na +/K + pump in the distal renal tubule leading to reabsorption of Na + and water from the urine, in exchange for K + and H +. Glucose spills over into the urine when the plasma concentration renal threshold for reabsorption (≈10mmol/L, but this varies between people, and is ↓ in pregnancy).

2 Bisphosphonates: These prevent bone resorption by inhibiting osteoclast activity. A single dose of pamidronate lowers Ca 2+ over 2–3d; maximum effect is at 1wk. Infuse slowly, eg 30mg in 300mL 0.9% saline over 3h via a largish vein. Max dose 90mg (see table 14.4). Zoledronic acid is significantly more effective in reducing serum Ca 2+ than previously used bisphosphonates. 8 Usually, a single dose of 4mg iv (diluted to 100mL, over 15min) will normalize plasma Ca 2+ within a week. se, flu symptoms, ↓PO 4 3−, bone pain, myalgia, nausea, vomiting, headache, lymphocytopenia, ↓Mg 2+, ↓Ca 2+, seizures.

3 Further management: Chemotherapy may help in malignancy. Steroids are used in sarcoidosis, eg prednisolone 40–60mg/d. Salmon calcitonin acts similarly to bisphosphonates, and has a quicker onset of action, but is now rarely used. nb: the use of furosemide is contentious, as supporting rct evidence is scant. 9, 10 It helps to promote renal excretion of Ca 2+, but can exacerbate hypercalcaemia by worsening dehydration. Thus it should only be used once fully rehydrated, and with concomitant iv fluids (eg 0.9% saline 1L/4–6h). Avoid thiazides.

Identify familial or 2° hyperlipidaemias, as ℞ may differ. Give lifestyle advice; aim for bmi of 20–25; encourage a Mediterranean-style diet—↑fruit, vegetables, fish, unsaturated fats; and ↓red meat; ↑exercise. Top ℞ priority are those with known cvd (there is no need to calculate their risk: ipso facto they already have high risk). Second ℞ priority is primary prevention in patients with chronic kidney disease or type-1 diabetes, and those with a 10-yr risk of cvd 10%, irrespective of baseline lipid levels.

• 1st-line therapy: Atorvastatin 20mg po at night, for primary prevention, and 80mg for secondary prevention and primary prevention in those with kidney disease. 27 Simvastatin 40mg, is an alternative. ↓cholesterol synthesis in the liver by inhibiting hmgcoa reductase. ci: porphyria, cholestasis, pregnancy. se: myalgia ± myositis (stop if ↑ ck ≥10-fold; if any myalgia, check ck; risk is 1 per 100 000 treatment-years), 28 abdominal pain, and ↑ lfts (stop if ast ≳100 u/L). Cytochrome p [link] inhibitors (p [link]) ↑serum concentrations (200mL of grapefruit juice ↑simvastatin concentration by 300%, and atorvastatin ↑80%, but pravastatin is almost unchanged).Current guidelines suggest a target plasma cholesterol reduction of ≥40 % in those with cvd.

• 3rd-line therapy: Alirocumab—a monoclonal antibody against pcsk9 (acts to reduce hepatocyte ldl receptor expression). Very effective in reducing ldl, 29 but expensive and needs to be given by injection every 2 weeks. Others: fibrates, eg bezafibrate (useful in mixed hyperlipidaemias); anion exchange resins, eg colestyramine; nicotinic acid (↑ hdl; ↓ ldl; se: severe flushes; aspirin 300mg ½h pre-dose helps this).