Lab Tests and Diagnostics: Haematology Basics

Haematology Basics

• Red Blood Cells (RBCs):
  • Main role: deliver oxygen to tissues and remove carbon dioxide
  • Lifespan: approximately 3 months
  • Main component: haemoglobin
• White Blood Cells (WBCs):
  • Neutrophils: migrate to sites of inflammation and remove foreign material (most abundant WBC)
  • Eosinophils: appear in response to mediators released from mast cells, raised in allergic conditions
  • Basophils, lymphocytes, and monocytes
• Platelets:
  • Damage caused to vascular endothelium is plugged by platelet aggregation

Definitions

• MCV (Mean Cell Volume): average volume of a single RBC
• PCV (Packed Cell Volume)/Haematocrit: ratio of the volume occupied by RBCs to the total volume of blood
• MCHC (Mean Cell Haemoglobin Concentration): average concentration of haemoglobin per unit weight of RBCs
• Macrocytic: large cells
• Microcytic: small cells
• -penia: reduced number of ...
• -cytosis: increased number of ...

Anaemia

• Definition: reduction from normal of the quantity of haemoglobin in the blood
• Causes:
  • Haemoglobin loss: haemorrhage (RBC loss) or haemolysis (RBC destruction)
  • Reduced haemoglobin synthesis: lack of nutrients, bone marrow failure, etc.
• Symptoms:
  • Hair loss
  • Eye yellowing
  • Chest pain
  • Irregular heartbeats
  • Pale skin
  • Spleen enlargement
  • Changes in stool odour
  • Shortness of breath
  • Muscle weakness
  • Fatigue
  • Dizziness
  • Memory problems

Classification of Anaemia

• Microcytic (MCV < 80fL): iron deficiency, thalassaemia
• Normocytic (MCV 80-100fL): anaemia of chronic disease (renal), sickle cell anaemia
• Macrocytic (MCV > 100fL): B12 deficiency, folate deficiency

Iron Deficiency Anaemia

• Most common cause of microcytic anaemia
• Lack of iron, essential component of haemoglobin
• RBCs are smaller in size
• Causes:
  • Chronic blood loss
  • Poor dietary intake
  • Malabsorption
  • Increased requirements (pregnancy)

Electrolytes and Minerals

• Magnesium:
  • Normal range: 0.7-1.0 mmol/L
  • Essential ion for enzymatic processes, ATP, and metabolic processes
  • Decrease in magnesium: critically ill patients, symptoms include muscle tremor, arrhythmias, loss of appetite, and fatigue
• Calcium:
  • Adjusted calcium: 2.2-2.6 mmol/L
  • Essential ion for skeletal structure, nerve conduction, and muscle contraction
  • Causes of hypercalcaemia: primary hyperparathyroidism, malignancy, thiazide diuretics, lithium, and calcium supplements
• Phosphate:
  • Normal range: 0.8-1.5 mmol/L
  • Essential for energy metabolism
  • Causes of hypophosphataemia: inadequate dietary intake, chronic renal failure, rhabdomyolysis, and tumour lysis
• Creatinine:
  • Produced at a fairly constant rate from muscles
  • Complete glomerular filtration with little reabsorption by renal tubules
  • Raised creatinine suggests poor renal function

Liver Function Tests (LFTs)

• Routine LFTs: give information about activity or concentrations of enzymes and compounds in the blood
• Need to be interpreted in the context of patient's baseline function, patterns of abnormalities, and clinical manifestations
• Useful in confirming or excluding a diagnosis of liver disease and monitoring its course### Anaemia
• A reduction from normal of the quantity of haemoglobin in the blood
• Caused by haemoglobin loss (haemorrhage or haemolysis) or reduced haemoglobin synthesis (lack of nutrients, bone marrow failure, etc.)

Symptoms of Anaemia

• Hair loss
• Eye yellowing
• Chest pain
• Irregular heartbeats
• Pale skin
• Spleen enlargement
• Changes in stool odour
• Shortness of breath
• Muscle weakness
• Fatigue
• Dizziness
• Memory problems

Classification of Anaemia

• Microcytic (MCV < 80fL): Iron Deficiency, Thalassaemia
• Normocytic (MCV 80-100fL): Anaemia Of Chronic Disease (Renal), Sickle Cell Anaemia
• Macrocytic (MCV > 100fL): B12 Deficiency, Folate Deficiency

Iron Deficiency Anaemia

• The most common cause of microcytic anaemia
• Lack of iron, an essential component of haemoglobin
• RBCs are smaller in size
• Caused by chronic blood loss, poor dietary intake, malabsorption, or increased requirements (pregnancy)

Differential Diagnosis

• Decreased MCV (5mmol/L)
• Hyperkalaemia: asymptomatic but fatal
• Elevated potassium: effects on the heart, leading to cardiac arrhythmias and cardiac arrest
• Causes: excessive intake, decreased elimination (renal failure), shift of potassium from cells to the plasma, and medicines (ACEI, ARBs, and potassium sparing diuretics)

Magnesium

• Normal range: 0.7-1.0 mmol/L
• Essential ion for enzymatic processes, ATP, and metabolic processes
• Decrease in magnesium: frequently seen in critically ill patients
• Symptoms: muscle tremor, arrhythmias, loss of appetite, and fatigue
• Causes: GI losses, increased renal excretion, surgery, trauma, infection, and malnutrition
• Medicines associated with hypomagnesaemia: cisplatin, ciclosporin, and laxatives

Calcium

• Adjusted calcium: 2.2-2.6mmol/L
• Best measure of calcium, taking into account albumin concentration
• Calcium is essential for maintaining skeletal structure and involved in nerve conduction and muscle contraction
• Causes of hypercalcaemia: primary hyperparathyroidism, malignancy, thiazide diuretics, lithium, and calcium supplements
• Causes of hypocalcaemia: severe malnutrition, hypoalbuminaemia, vitamin D deficiency, renal and liver disease, bisphosphonates, chemotherapy, and furosemide

Phosphate

• Normal range: 0.8-1.5mmol/L
• Major function: energy metabolism
• Causes of hypophosphataemia: inadequate dietary intake, severe malnutrition, chronic renal failure, and hyperparathyroidism
• Causes of hyperphosphataemia: tumour lysis, rhabdomyolysis, and chronic renal failure

Creatinine

• Produced at a fairly constant rate from muscles
• Undergoes complete glomerular filtration with little reabsorption by the renal tubules
• Clearance is often a good indicator of renal function
• Raised creatinine: poor renal function
• Serum creatinine level: used to calculate CRCL or eGFR to estimate renal function and aid drug dosing

Liver Function Tests (LFTs)

• Routine LFTs: give information about the activity or concentrations of enzymes and compounds in the blood
• Need to be interpreted in the context of the patient's baseline function, patterns of abnormalities, and clinical manifestations
• Useful in confirming or excluding a diagnosis of liver disease and monitoring its course

Albumin

• Normal range: 34-50g/L
• Protein produced by the liver
• Roles: maintaining blood pressure, binding to and carrying endogenous compounds, and medicines
• Decrease in albumin: increased volume of distribution, shift of albumin from the serum to interstitial fluid, increased loss of albumin, and reduced production of albumin

Bilirubin

• Normal range: greater than 19 micromoles/L
• Breakdown product of RBCs
• Transported to the liver by albumin
• Conjugated with glucuronic acid and excreted into bile and eventually the faeces
• Used as a marker of overall liver function and specifically jaundice
• Increase in bilirubin: increased production, hepatitis, cirrhosis, hepatic tumours, and medicines

Liver Enzyme

• Reference ranges: Alanine Transaminase (ALT) < 45 U/L, Aspartate Transaminase (AST) < 35 U/L, Alkaline Phosphatase (ALP) 32-120 U/L, Gamma-Glutamyl Transpeptidase (GGT) < 70 U/L

Inflammatory Markers

• C-Reactive Protein (CRP)
• Protein made by the liver, released into the bloodstream within a few hours of tissue injury, the start of infection, or another source of inflammation
• Not diagnostic for a specific disease but provides information on whether inflammation is present
• Causes of increased CRP: acute infection, flare of IBD, RA, post MI, or post-surgery

Erythrocyte Sedimentation Rate (ESR)

• Indirect measurement of inflammation in the body
• Measures the rate of fall (sedimentation) of erythrocytes (RBCs)
• Normally, red cells fall slowly, leaving little clear plasma
• Increased blood levels of certain proteins, which are increased in inflammation, cause the red blood cells to fall more rapidly, increasing the ESR
• Causes of increased ESR: sickle anaemia, acute infection, myeloma, and diseases associated with inflammation

Blood Gases, pH

• Normal range: 7.35-7.45
• Normal physiological pH: needed for many physiological functions, including enzymatic reactions and oxygen release from haemoglobin
• Mechanisms to maintain optimal pH: respiratory and metabolic
• Acidosis: pH < 7.35
• Alkalosis: pH > 7.45

Troponin

• Proteins in muscle fibres that help regulate muscle contraction
• Released into the bloodstream when there is damage to the heart muscle
• Increase in troponins: indicate damage to cardiac muscle
• Used alongside an ECG and symptoms of ischaemia to diagnose ACS
• May also be raised in other cardiac conditions where there is damage to the cardiac muscles