Bloods

Question 1

Calcium

Answer 1

Reference range: 2.05 – 2.60 mmol/L.
Role
Bones and teeth, blood clotting, neurotransmitter release, muscle and nerve excitability.
Homeostatis
Hypocalaemia: parathyroid hormone (↓ osteoblast bone deposition, ↑ osteoclast reabsorption, ↓ calcium loss in urine, ↑ formation of calcitriol (↑ rate of dietary calcium)).
Hypercalaemia: thyroid calcitonin (↑ osteoblast bone deposition, ↓ osteoclast reabsorption).

Question 2

Hypercalcaemia

Answer 2

Hypercalcaemia
Aetiology
Malignancy (50%, often with hypoalbuminaemia; myeloma activating osteoclasts, eptopic parathyroid hormone like peptide: hypernephroma, ovarian tumour, bronchial carcinoma), primary hyperparathyroidism (20%, young), vit D toxicity, Paget’s disease, chronic granulomatous disease (extrarenal synthesis of calcitriol).
Clinical features
Bones (fractures, pain), stones, abdominal groans (abdo pain, constipation, nausea and vomiting), psychiatric moans (depression, confusion, psychosis).
Polyuria (↓ sensitivity to ADH), polydipsia, lethargy, weakness.
Management
Find and treat underlying cause.
Stop thiazide diuretics (worsens hypercalcaemia), ↑ oral salt and water (↑ calcium excretion, avoids volume depletion which would exacerbate hypercalcaemia).
Complex further management: includes loop diuretics (furosemide), and bisphosphonates.

Question 3

Hypocalcaemia

Answer 3

Aetiology
Hyperventilation (transient), ↓ consumption, ↑ calcium loss, ↑ phosphate, hypoparathyroidism, salicylate poisoning, excessive blood transfusions (citrate), vitamin D deficiency (↓ consumption, malabsorption, lack of sunlight, kidney or liver failure).
Clinical features
Tingling in extremities, hyperactive reflexes, muscle cramps, tetany (Trousseau’s sign: forearm compression causes spasm of hand. Chovstek’s sign: tapping on facial nerve, in front of ear, causes contraction of eye muscles), stridor (laryngeal spasm), convulsions, fractures, malaise to psychosis.
Investigations
ECG: prolonged QT interval.
Uraemia, ↑ serum creatinine indicates chronic renal failure.
Hypoparathyroidism due to hypomagnesaemia uncorrected by calcium.
↑ serum phosphate, normal renal indicates hypoparathyroidism.
Management
Symptomatic or corrected serum calcium <= 1.875:
Calcium gluconate IV.
Asymptomatic or mild hypocalcaemia:
Oral calcium and vitamin D (between meals).

Question 4

Sodium

Answer 4

Reference range: 135 – 145 mmol/L.
Role
Fluid / electrolyte balance (50% of osmolarity), muscle and nerve generation and conduction of action potentials.
Homeostatis
Low renal blood flow: renin system → aldosterone (distal renal tubule sodium pump reabsorbs sodium in exchange for K+ and H+).
High plasma osmolality (including sodium): thirst and posterior pituitary release of ADH (anti-diuretic hormone; vasopressin) (renal collecting duct aquaporins open to passively reabsorb water,  ↓ serum sodium concetration).
High atrial stretch: ANP (atrial natriuretic peptide) (↓ rennin & ADH; ↑ glomerular filtration rate).

Question 5

Hypernatraemia

Answer 5

Aetiology
Hypovolaemic: inadequate intake (most common cause; elderly, disabled), excessive urinary loss (glucosuria, osmotic diuretics), sweating, watery diarrhoea.
Euvolaemic: diabetes insipidus.
Hypervolaemic: hypertonic fluid (↑ concentration of solutes compared to body; IV fluids, seawater), mineralcorticoid (Conn’s, Cushing’s).
Clinical features
Thirst, oedema, confusion. Severe: seizures, coma.
Management
Oral rehydration, if possible.
Hypovolaemic: 0.9% saline (less marked shift).
Eu/hypervolaemic: 5% dextrose IV slowly (~4L/24hrs) guided by urine output and serum sodium

Question 6

Hyponatraemia

Answer 6

Aetiology
Diuretics (especially thiazides), water excess (oral or excess 5% dextrose IV), Addison’s, renal failure, diarrhoea and vomiting, SIADH (↑ADH: Na dilution), pancreatitis, lung small cell carcinoma (ectopic ADH, 1st sign of cancer?), and many many others.
Clinical features
Mild: headache, nausea, lethargy.
Moderate: confusion, weakness, vomiting.
Severe: cerebral oedema: coma, seizures, respiratory failure.
Rapid changes in serum sodium levels or severe hyponatraemia can cause symptoms of vomiting, headache, drowsiness, seizures, coma, and cardio-respiratory arrest.
Chronic hyponatraemia can lead to increased risk of falls, bone fractures, osteoporosis, gait instability, and concentration and cognitive deficits.
Investigations
Urine sodium and osmolarity (helps find cause).
Management
Complex treatment. Slow correction required.
Assess hydration (thirsty, vomiting, diarrhoea, sweating, not drinking, oliguria with urinary concentration, sunken eyes, dry mucus membranes, JVP, wet chest, fluid chart).
Correct underlying cause if possible.
Hypovolaemic: replace lost fluids with 0.9% saline. Bolus challenges with regular reassessment.
Normovolaemic: slow 0.9% saline over several days (max 15mmol/day).
SIADH: fluid restrict, demeclocycline (antibiotic who’s side-effect is this induction of Diabetes Insipidus!), find cause.
Oedematous: find and treat underlying cause.

Question 7

Potassium

Answer 7

Reference range: 3.5 – 5.2 mmol/L.
Role
Nerve impulse propagation and muscle contraction, pH regulation by H+ exchange.
Homeostatis
90% is intracellular (mostly muscle cells). Extracellular K+ and H+ vary together because they compete with each other in exchange for Na+ across cell membranes and kidney distal tubule (sodium reabsorbed from urine). Insulin and catecholamines stimulate K+ uptake into cells by stimulating Na+/K+ pump.

Question 8

Hyperkalaemia

Answer 8

Aetiology
Oliguric renal failure, K+ sparing diuretics (spironolactone: aldosterone antagonist), cell release (rhabdomyolysis, burns, massive blood transfusions), acidosis (so much H+ for kidneys to excrete, K+ gets retained), artifact (haemolysed sample), excess K+ therapy, Addison’s (hyperaldosteronism), ACEi, hyperglycaemia (low insulin).
Clinical features
Cardiac arrhythmias (VT, VF), palpitations, arrest (>9mmol).
Tall tented T waves (in all leads), flattened P waves, wide PR interval and QRS complex.
Paraaesthesia, weakness, paralysis.
Investigations
K+ > 6.5: urgent ECG (any ECG changes requires immediate emergency treatment without further investigations).
K+ <6.5 or no ECG changes: repeat bloods (without tourniquet if possible), venous blood gas (acid-base status).
Management
Emergency: do both of the following immediately
Temporarily ↓ risk of arrhythmia: cardiac membrane stabilization, no ↓ in serum potassium
10mL of 10% calcium gluconate IV over 10 minutes (ideally with cardiac monitoring). ECG corrects within 3 minutes: repeat until ECG returns to normal.
Temporarily shift K+ into cells: not always needed if cause apparent and quickly resolvable.
10units of Insulin actrapid in 50ml of 50% dextrose over 10 minutes. ↓ serum K+ by 1mmol after 30 mins lasting 4 hours.
5mg nebulized salbutamol. Peak 60 minutes, shorter duration, unpleasant side-effects.
Remove K+ from body:
Renal excretion: IV fluid (if not renal failure), relief of urinary tract obstruction.
GI excretion: calcium resonium (binding resin) 30g TDS PO, with laxative. Takes hours to work, can be useful medium term holding measure.
Dialysis: severe renal failure or all else fails.
Chronic hyperkalaemia:
Serum K+ 5.3 to 6.0 usually well tolerated, but risk of severe hyperkalaemia with illness, drug or dietary indiscretion.
Acute kidney injury: specialist advice.
CKD 4-5: review medication and diet (renal dietitian); treat acidosis; consider diuretics, binding resins, or dialysis.
Preserved renal function: review medication, specialist opinion

Question 9

Hypokalaemia

Answer 9

Aetiology
Common: diuretics (especially furosemide, bendroflumethiazide), diarrhoea, laxatives, vomiting and metabolic alkalosis (not enough H+ for kidneys to excretion, so use K+ instead).
Uncommon: 1o hyperaldosteronism (Conn’s syndrome), 2o hyperaldosteronism (renal artery stenosis), hypomagnesaemia, drugs (mineralocorticoids, insulin, beta agonists).
Clinical features
Moderate: muscle weakness, constipation, polyuria, polydipsia.
Severe: flaccid paralysis, ileus, hyporeflexia, tetany.
Flattened T waves. Prolonged QT interval, leading to arrhythmias.
Investigations
ECG.
Repeat bloods (inc Mg), but treat immediately if cause is evident.
If cause unclear consider venous blood gas (pH) and urinary potassium excretion.
Management
Mild (>2.5): oral supplementation (if on diuretics use K+-sparing).
Severe (<2.5): IV supplementation (no more than 20mmol/hr through peripheral line due to pain). Difficult to correct with low magnesium.
Try to correct underlying cause.

Question 10

Creatinine

Answer 10

Reference range: 70 – 150 µmol/L.
Role
Proportional to muscle mass. Usually produced at a more steady rate compared to urea. Virtually all excreted by the kidneys.
Plasma creatinine is used as a measure of renal function.
Plasma creatinine is not a sensitive marker for changes in GFR when renal function is near normal, or high. People may lose 50% of normal GFR and have a borderline high creatinine, (e.g., 150).
High Creatinine
Destruction of muscle.
High dietary intake of meat
Hypothyroidism
Testosterone therapy
↑ musculature (Afro-Caribbean race, bodybuilding, ↑ protein intake).
Drugs (cimetidine, trimethoprim, sulphamethoxazole, cephalosporins, corticosteroids, ACEi and vitamin D metabolites).
Low Creatinine
↓ muscle mass (age-related decline, females, malnutrition, muscle wasting, amputation).
Vegetarian diet (decrease in creatinine generation).
Hyperthyroidism.

Question 11

Urea

Answer 11

Reference range: 2.5 – 6.7 mmol/L.
Role
Formed in liver via urea cycle from ammonia (produced by deamination of amino-acids; waste nitrogen) – principal end-product of protein catabolism and constitutes half of urinary solids.
Uraemia – High Urea
Aetiology
Pre-renal:
↑ hepatic production of urea:
High protein diet.
GI haemorrhage (expect Hb drop).
↑ protein catabolism (trauma, major surgery, starvation, Ca).
↑ renal reabsorption of urea (reduced renal perfusion: cardiac failure, shock, severe diarrhoea).
Iatrogenic - ↑ production (tetracyclines, corticosteroid).
Renal:
Acute or chronic renal failure.
Post-renal:
Urinary outflow obstruction.
Clinical features
Neuro: twitch / tremor, fits, encephalopathy, neuropathy.
GI: anorexia, nausea, vomiting, colitis.
Respiratory: pleuritis, pleural effusion.
Skin: pruritus, “half-and-half” nails (white, demarcation, pink).
Nalitosis, perocarditis, growth retardation, sexual dysfunction.
Investigations
As renal failure.

Question 12

Haemoglobin

Answer 12

Reference range: ♀ 11.5 – 16 g/dL ♂ 13 – 18 g/dL.
Role
RBC protein iron-containing oxygen-transport, developed in bone marrow.
Oxygen dissociation curve: ↓pH causes ↓Hb affinity for O2
↓ lung CO2 causes Hb to take up O2.
↑ tissue CO2 causes Hb to give up O2.

L shift: fetal haemoglobin (fetus takes O2 from mother).
R shift (Bohr effect): ↑CO2, ↑temperature, acidosis

Question 13

Haematocrit

Answer 13

Also known as Packed Cell Volume (PCV).
Reference range: ♀ 36-48% ♂ 40-52%.
Definition
Proportion of blood volume that is occupied by RBCs. Elevated HCT associated with ↑ thrombotic events and cardiovascular mortality.
Elevated
↓ plasma volume: dehydration (alcohol, diuretics, acute pancreatitis, Addison’s).
↑ red cell mass: primary (polycythaemia rubra vera), secondary (COPD, smoking, altitude, EPO use, steroids, Dengue fever).
Lowered
Acute haemorrhage (if RDW normal).
Anaemia (use MCV and RDW).

Question 14

Mean cell volume (MCV)

Answer 14

Reference range: 80 – 96 fl
Definition:
Measure of the average red blood cell volume (i.e. size).
It can be calculated (in litres) by dividing the hematocrit by the red blood cell count (number of red blood cells per litre).
Macrocytic Anaemia  MCV (>96fL)
Megaloblastic: large erythroblasts in marrow (with delayed nuclear maturation) Do not treat with blood!
Vitamin B12 deficiency.
Pernicious anaemia.
Folate deficiency.
Normoblastic:
Alcohol excess or liver disease.
Reticulocytosis ( immature RBCs (reticulocytes) in blood stream).
Myelodysplastic syndromes.
Hypothyroid.
Drugs (e.g., cytotoxics, anti-folate drugs: phenytoin).
Normocytic Anaemia normal MCV (80 – 96)
Chronic Disease  or normal MCV.
Acute blood loss.
Renal failure (loss of EPO).
Pregnancy (dilutional).
Hypoparathyroidism: or ↑MCV.
Haemolytic anaemia.
Bone marrow failure.
Microcytic Anaemia  MCV (<80fL)
Chronic Disease  or normal MCV.
Iron-deficiency anaemia ( MCV, MCHC (hypochromic),  serum ferritin,  total iron-binding capacity). If blood in stool, likely GI ca.
Sideroblastic anaemia ( MCV, MCHC,  serum iron, histology shows iron ring).
Thalassaemia (MCV, normal serum iron, normal serum ferritin, absent marrow iron).

Question 15

Red blood cells, rdw and mch

Answer 15

Reference range: ♀ 3.8 – 5.8 g/dL ♂ 4.5 – 6.5 g/dL.
Definition: Number of RBC per volume of blood.
High: polycythaemia.
Low: anaemia or erythrblastopenia.

Red Cell Distribution Width (RDW)
Reference range: 11.6 – 14.0 %
Definition
Misleading name, actually measure of variation of RBC width. RBCs normally standard size, some disorders introduces variation in size.
Mainly used to differentiate anaemia of mixed cause from anaemia of single cause:
Vitamin B12 deficiency: ↑MCV, normal RDW.
Mixed B12 and iron anaemia: ↑RDW.

Mean Cell Haemoglobin (MCH)
Reference range: 27.0 – 32.0 pg
Definition
Average mass of hemoglobin per red blood cell in a sample of blood. It is calculated by dividing the total mass of hemoglobin by the number of red blood cells in a volume of blood.

Question 16

Mean Cell Haemoglobin Concentration (MCHC)

Answer 16

Reference range: 4.9 to 5.5 mmol/L
Definition
Concentration of hemoglobin in a given volume of packed red blood cell. It is calculated by dividing the hemoglobin by the hematocrit.
It is diminished (“hypochromic”) in microcytic anemias, and normal (“normochromic”) in macrocytic anemias (due to larger cell size, though the hemoglobin amount or MCH is high, the concentration remains normal). MCHC is elevated in hereditary spherocytosis.

Question 17

Platelets

Answer 17

Reference range: 150 – 400 x109/L
Definition
Anuclear cells, which live for approximately 9 days, for primary homeostatic plug to counter immediate bleeding.
Thrombocytosis (High)
Aetiology
Reactive (85%): inflammation (including surgery), infection (highly raised with a collection), haemorrhage, iron deficiency, malignancy, following splenectomy (↓ breakdown).
Essential: myeloproliferative disorders.
Clinical features
Thrombosis, and paradoxically haemorrhage.
Investigations
Complex, involve haematologist.
Management
Reactive: often no treatment.
Essential: aspirin, hydroxyurea.
Thrombocytopaenia (Low)
Aetiology
↓ production: B12 or folic acid deficiency, leukaemia, myelodysplastic syndrome, liver failure, infection, various hereditary syndromes.
↓ survival: idiopathic or thrombotic thrombocytopenic purpura, haemolytic-uraemic syndrome, DIC, SLE, hyperspenism, HIV.
Clinical features
Purpura, mucous membrane bleeding, epistaxis, menorrhagia, post-partum haemorrhage.
Investigations
Complex, involve haematologist.
Management
Treat underlying condition.

Question 18

White Cell Count (WCC)

Answer 18

Reference range: 4 – 11 x109/L
Definition
Leukocytes (white blood cells) are cells of the immune system defending the body against both infectious disease and foreign materials. Found throughout the body, including the blood and lymphatic system.
Granulocytes (polymorphonuclear : neutrophils, basophils, eosinophils) have membrane-bound enzymes which digest endocytosed particles.
Agranulocytes (mononuclear: lymphocytes, monocytes, macrophages) have non-specific azurophilic granules, which are lysosomes.
Leukocytosis (high)
Viral, bacterial, fungal, or parasitic infection, cancer (including blood malignancies), hemorrhage, and drugs (corticosteroids, lithium, beta agonists), inflammatory conditions.
Leukopenia (low)
Also known as leukocytopenia.
Chemotherapy, radiotherapy, leukaemia, myelofibrosis, aplastic anemia, drugs (immunosuppressives, valproic acid), HIV, influenza, SLE, Hodgkin’s lymphoma, some types of cancer, typhoid, malaria, TB, spleen enlargement, folate deficiencies.

Question 19

Neutrophils

Answer 19

Reference range: 2 – 7.5 x109/L (40-75% of WBC)
Definition
Defend against bacterial or fungal infection. Activity and death in large numbers forms pus. Systemic effects of fever by releasing endogenous pyrogen.
Neutrophilia
Bacterial infection, surgery, burns, trauma, haemorrhage, infarction, inflammation, polymyalgia, myeloproliferative disorders, leukaemias, drugs (e.g., steroids).
Neutropaenia
Aetiology
↓ production: marrow aplasia, marrow infiltration, viral infections, TB, brucellosis, megaloblastic anaemia.
↑ consumption: septicaemia (neutrophils used up), hypersplenism (neutrophils destroyed), autoantibodies (e.g., SLE, neutrophils destroyed).
Most common life threatening emergency in oncology. Neutropenia <0.5 leaves patient open to infection (catheterization, cannulas, wounds, hospital environment).
Clinical features
May be asymptomatic.
Fever, lethargy, SOB, cough, confusion, tachycardia, ↓BP, ↑RR, low sats, rash.
Investigations
CXR, blood cultures, stool culture, MSU, sputum.
Management
Neutropaenia <0.5: immediate medical / haematological review.
Pyrexia in neutropenia patients: blood cultures then a/b – do not wait for results before starting a/b, patient may die.

Question 20

Lymphocytes

Answer 20

Lymphocytes
Reference range: 1.3 – 3.5 x109/L (20-45% of WBC)
Definition
Lymphocytes (T, B and natural killer) are found in the blood, lymph and organised lymphoid tissues such as the lymph nodes and spleen, where they function to orchestrate and effect immunity.
T and B lymphocytes exhibit memory and specificity and, as such, are responsible for the unique quality of the adaptive immune system.
Lymphocytosis (high)
Viral infections, chronic intracellular bacterial infections (TB, brucellosis), ALL, CLL.
Lymphocytopenia (low)
Steroids, uraemia, SLE, Legionnaire’s disease, malignancies of bone marrow (leukaemia), post chemo or radiotherapy, AIDS.

Question 21

Eosinophil

Answer 21

Reference range: 0.04 – 0.44 x109/L
Definition
Immune and allergic reactions. Instrumental in fight against parasites that are too big to be phagocytosed.
Eosinophilia (high)
Parasitic infections, collagen vascular disease (Rheumatoid arthritis), malignancies (Hodgkin’s disease), skin disease (dermatitis), Addison’s disease, oesophagitis.

Question 22

Basophil

Answer 22

Reference range: 0.01 – 0.11 x109/L
Definition
Basophils are related to connective tissue mast cells. They share a similar functional mechanism and role in type I IgE hypersensitivity and anaphylaxis.
Basophilia (high)
Viral infections, urticaria, post-splenectomy, myxodema,ulcerative colitis, systemic mastocytosis, malignancy, myeloproliferative disorders, haemolysis.

Question 23

Monocyte

Answer 23

Reference range: 0.2 – 0.8 x109/L
Definition
Monocytes are the largest WBC, and are the precursors of macrophages. Together, the two types of cell make up the reticulo-endothelial system.
Monocytic function includes (1) transforming into a macrophage at the site of inflammation in order to undertake phagocytosis, (2) processing antigen for lymphocyte recognition, (3) removal of senescent blood cells.
Monocytosis (high)
Myelodysplasia, Hodgkin’s lymphoma, infections (TB, brucellosis, malaria, infective endocarditis).

Question 24

Magnesium (Mg)

Answer 24

Reference range: 0.75 – 1.0 mmol/L.
Role
Essential component of soft tissues and bone (1% extracellular). Required for the normal functioning of muscle and nervous tissue, exerting effects similar to calcium and acts directly at the motor endplate. Important activator ion participating in the function of many enzymes involved in phosphate transfer reactions.
Changes in plasma magnesium usually induce changes in calcium. Hypomagnesaemia impairs PTH secretion and may also impair end organ response to PTH.

Question 25

Hypermagnesaemia

Answer 25

Aetiology
Renal failure, iatrogenic, hypothyroidism, lithium, milk alkali syndrome.
Clinical features
Symptoms when >2 mmol/l.
Muscle weakness, confusion, respiratory paralysis, cardiac arrest.
ECG: ↑PR interval, broadened QRS complex. or elevated T waves.
Management
Treatment underlying cause.
Calcium chloride IV (Mg antagonistic), haemodialysis.

Question 26

Hypomagnesaemia

Answer 26

Aetiology
↓ uptake (rare because magnesium is ubiquitous): Kwashiorkor, severe alcoholism, malabsorption, parenteral nutrition without adequate Mg.
↑ loss: DKA, steatorrhea, IBD (Crohn’s > ulcerative colitis), prolonged vomiting or diarrhoea, hyperaldosteronism, mannitol-induced dieresis.
Miscellaneous: excess vitamin D therapy, hyperparathyroidism, postparathyroidectomy, drugs (cisplatin, gentamicin).
Clinical features
Similar to hypocalcaemia: muscle twitching, irritability, tetany, aggression and convulsions.
Ventricular arrhythmias (such as torsade de pointes).
Management
Magnesium IV, with levels monitored.
Potassium and calcium supplementation may be required
Chronic hypomagnesaemia: Mg oxide PO.
Refeeding Syndrome Bloods: magnesium, phosphate, calcium (bone).

Question 27

Phosphate (PO43-)

Answer 27

Reference range: 0.8 – 1.5 mmol/L.
Role
Membrane structure, energy storage, transport in all cells, required for production of ATP, component of DNA and RNA. 85% of body’s phosphorus is bone, 15% soft tissue, 0.1% extracellular fluid.
Phosphorus homeostasis regulated by several hormones: Parathyroid hormone (phosphate released from bone, inhibits renal reabsorption), Vitamin D (intestinal reabsorption of phosphorus), thyroid and growth hormones (↑ renal reabsorption).
Calcium and phosphate ion physiology is closely related. If the product of the concentration of each ion exceeds a value that is termed their solubility product, they precipitate out of solution. This can result in new mineralization within bone or ectopic calcification. Conversely, the equilibrium results in one ion being reabsorbed from bone if the concentration of the other drops.  large ↓ in plasma phosphate can cause hypercalcaemia.

Question 28

Hyperphosphataemia

Answer 28

Aetiology
↑ intake: excessive vitamin D, infants on excessive amounts of high phosphate feeds, TPN with excessive phosphate concentration.
↓ excretion: renal failure, with or without secondary hyperparathyroidism, hypoparathyroidism.
Redistribution: therapeutic destruction of cells in malignancy, reduced celluar uptake in insulin deficiency.
Acromegaly (hyperphosphataemia and hypercalcaemia may occur).
Acidosis.
Clinical features
Signs of hypocalcaemia.
Muscle cramps, confusion, seizures, hypotension, heart failure.
Management
Normal treatment of hypocalcaemia.
Phosphate binders may be considered.

Question 29

Hypophosphataemia

Answer 29

Aetiology
Alcohol withdrawal, primary hyperparathyroidism, osteomalacia, rickets, acute liver failure, Fanconi’s syndrome, prolonged IV glucose administration, DKA (this condition is associated with severe phosphate depletion, no studies have shown benefit with the addition of phosphate to the DKA treatment regimen).
Clinical features
Muscle weakness, cardiac compromise.
Management
Asymptomatic: correct cause, dietary or oral phosphate.
Symptomatic: correct cause, IV phosphate.

Question 30

CRP

Answer 30

Reference range: <5 mg/L.
Role
Acute phase protein. ↑ with tissue damage (infection, inflammation, tissue injury or necrosis). Manufactured in liver, and levels not effected by therapeutic treatments (only liver damage) – reliable measure.
Rises 6 hours after stimulus, peak at 48 hours. Half life 19 hours. CRP is better than ESR for monitoring fast changes as it does not depend on fibrinogen or immunoglobulin levels, and is not affected by red blood cell numbers and shape.
Uses: infection (more marked in bacterial than viral), inflammation, tissue necrosis, trauma (burns, surgery, fractures), neoplasia.

Question 31

ESR

Answer 31

Reference range: vary based on gender and age.
♂ ESR = age / 2.
♀ ESR = (age +10) / 2.
Role
Ability of RBCs to form rouleaux, determined by levels of acute phase proteins, fibrinogen and immunoglobulin. Measures distance RBCs fall after one hour in a vertical column of anticoagulated blood under the influence of gravity.
↑ ESR
Malignancy: lymphoma, colon, breast.
Haematologic: myeloma (high ESR plus osteoporosis equals multiple myeloma until proved otherwise), anaemia.
Connective tissue disorders: SLE, rheumatoid arthritis, polymyalgia rheumatica, temporal arteritis, systemic sclerosis.
Infections: TB, acute hepatitis, bacterial.
Others: sarcoidosis, renal diseases, drug fever, hepatic cirrhosis, pregnancy.
↓ ESR
Polycythaemia (vera or secondary).
Conditions which feature abnormal red blood cells (sickle cell anaemia, hereditary spherocytosis, acanthocytosis).
Microcytosis (iron deficiency).
Hypofibrinogenaemia (disseminated intravascular coagulation, massive hepatic necrosis).
Over anticoagulation.
High white blood cell count.
Cachexia.
Heart failure.

Question 32

Plasma viscosity

Answer 32

Reference range: 1.5 – 1.7 mPa/s.
Role
Plasma viscosity is affected by the concentration of large plasma proteins, particularly those with pronounced axial asymmetry - fibrinogen and some immunoglobulins. Plasma viscosity is not affected by anaemia (unlike ESR).
Lower levels of plasma viscosity are seen in neonates because of lower levels of proteins, particularly fibrinogen. There is a slight increase in viscosity in the elderly as fibrinogen increases. There is no difference between males and females.

Question 33

Bilirubin

Answer 33

Reference range: 3 – 17 µmol/L.
Role
Bilirubin is a bile pigment produced by the breakdown of haem and reduction of biliverdin. Unconjugated bilirubin is insoluble in plasma unless bound to protein, mainly albumin. Salicylates, sulphonamides, non-esterified fatty acids and reduced pH levels result in decreased protein-binding of unconjugated bilirubin. Normally, 95% of the circulating bilirubin is unconjugated.
The bilirubin-albumin complex is dissociated by receptors on hepatocytes. The albumin remains in the plasma. The bilirubin is taken into the hepatocyte and conjugated by the enzyme bilirubin UDP-glucuronyl transferase to form bilirubin diglucuronide. It is this water-soluble glucuronate derivative which is excreted into the biliary system.

In the gut, principally the colon, bilirubin glucoronides are degraded by bacteria and converted into a mixture of compounds, known as urobilinogen or stercobilinogen; these are water soluble.
Most of the urobilinogen is excreted in the faeces where it is oxidised to urobilin which is brown. Some is reabsorbed into the liver where it is re-excreted. When the amount of urobilinogen is increased, some passes into the systemic circulation and is excreted in the urine.
Complete biliary obstruction is indicated by (a) absence of urinary urobilinogen, (b) presence of urinary bilirubin.

Question 34

Hyperbilirubinaemia

Answer 34

Hyperbilirubinaemia
Aetiology
Pre-hepatic Jaundice
The most common cause of a pre-hepatic jaundice is physiological neonatal jaundice (two days after birth).
Haemolytic anaemia, haemolysis (hereditary spherocytosis), ineffective erythropoiesis (pernicious anaemia), severe rhabdomyolysis with release of myoglobin, haemorrhage (e.g., sports injuries), congenital deficiency of conjugating enzymes (Gilbert’s syndrome, Crigler Najjar syndrome), breast milk jaundice, drugs (rifampicin).
Hepatic Jaundice
The most common causes of hepatic jaundice are: viral hepatitis, alcoholic hepatitis, cirrhosis, primary biliary cirrhosis, hepatic metastases.
Less common causes include: drug-induced (paracetamol, halothane, methyldopa, barbiturates), leptospirosis, liver abscess.
Rare causes include: benign intrahepatic cholestasis of pregnancy, benign recurrent intrahepatic cholestasis, cardiac failure, Wilson’s disease, Hodgkin’s disease, Budd-Chiari syndrome, Dubin-Johnson syndrome, Rotor’s syndrome.
Obstructive Jaundice
The most common causes are: gallstones in the bile duct, carcinoma of the head of the pancreas.
Obstruction of the lumen of the bile ducts: gall stones, parasites (hydatid disease, liver fluke, round worms), iatrogenic (post-T-tube cholangiography).
Mural obstruction: congenital atresia, traumatic stricture (ampullary stricture), sclerosing cholangitis, cholangiocarcinoma.
Extramural obstruction: carcinoma of the head of pancreas, carcinoma of the ampulla of Vater, pancreatitis, porta hepatis tumours (often secondary deposits), chronic duodenal ulceration.
Drugs (isoniazid, chlorpromazine).

Question 35

Albumin

Answer 35

Reference range: 35 – 50 g/L.
Role
Albumin is the most important contributor to the maintenance of plasma colloid oncotic pressure; deficiency results in oedema.
It is an important non-specific carrier protein for molecules such as fatty acids, calcium, unconjugated bilirubin, thyroxine and urate. It may carry drugs that can displace these endogenous substances; for example, salicylates and sulphonamides may displace bilirubin.
Plasma albumin alone is an insensitive and non-specific marker of the level of nutrition. This is because its concentration is affected by a number of factors e.g. its distribution between body compartments and its prolonged half-life.
However, in the presence of historical and physical stigmata of malnutrition, an albumin value of 32 g / l or less is a key index of severe malnutrition.
Alternative plasma proteins may be more sensitive and specific for malnutrition due to their shorter half lives and simpler kinetics. These include transferrin and prealbumin.
Hyperalbuminaemia
Severe dehydration, arm cuffed for too long.
Hypoalbuminaemia
Congenital: analbuminaemia - rare; plasma albumin usually <1.0 g/l. Often asymptomatic due to compensatory ↑ in plasma globulins.
Reduced synthesis: chronic liver disease (not acute due to large hepatic reserve and long half-life of albumin - 20 days), severe malnutrition.
Increased catabolism: trauma, surgery, infection, malignancy.
Increased losses: renal (proteinuria, especially the nephrotic syndrome), skin (exfoliative dermatitis, severe burns), GI tract (haemorrhage, protein losing enteropathies).
Altered distribution: serous effusion (ascites), overhydration.

 

Question 36

ALT

Answer 36

Reference range: 3 – 50 iu/L.
Role
Transfers alanine to ketoacid, producing pyruvate, mainly in hepatocytes,  good indicator of liver activity. 20-80x increase with cirrhosis, 40-3000x increase with hepatitis, up-to 10000x increase for toxic or ischaemic injury.
↑ ALT
Alcohol abuse, drugs, chronic hepatitis B and C, non-alcoholic fatty liver disease, autoimmune hepatitis, haemochromatosis, Wilson’s disease, α1-antitrypsin deficiency, coeliac disease, inherited and acquired muscle diseases, exercise.

Question 37

ALP

Answer 37

Reference range: 30 – 200 iu/L.
Role
Alkaline phosphatase is an enzyme which catalyzes the hydrolysis of phosphate monoesters. It is membrane-bound and widely found: liver (55%; in hepatocytes next to biliary canaliculi), bone (45%; osteoblasts), gut (5%), kidney, placenta.
Total serum alkaline phosphatase is normally measured but liver and bone isoenzymes may be distinguished if required. They are normally present in roughly equal amounts within plasma. Gut ALP rises after meals, especially in those of blood group B or O who are secretors of blood group substances. Bone ALP increases at the time of physiological growth spurts. Placental ALP normally increases at the end of the third trimester.
↑ ALP
Hepatobiliary disease: cholestasis (↑ synthesis of hepatocyte ALP and ↑ secretion of high molecular weight form into plasma; ↑ALP 10x), hepatocyte disease (viral hepatitis; ↑ALP moderate).
Bone disease (↑osteoblastic activity): Paget’s disease, osteomalacia and rickets, renal osteodystrophy, bone metastases, primary bone tumour (e.g. sarcoma), recent fracture, growing child (especially at puberty).
Pregnancy. Malignancies (e.g. seminomas).
Distinguishing between hepatic and bone: GGT, ALT, electrophoresis separation of isoenzymes, bone scan, ultrasound scan of liver.
↓ ALP
Vast number of possible causes.
Cardiac surgery and bypass, malnutrition, ↓Mg, hypothyroidism, severe anaemia.

Question 38

GGT

Answer 38

Reference range: ♀ 7 – 32 iu/L ♂ 11 – 50 iu/L.
Role
Gamma GT is an enzyme which is found in hepatocytes and biliary epithelial cells. GGT may be high in liver disease. In particular it is a feature of biliary outflow obstruction rather than hepatocellular damage.
↑ GGT
GGT serum measurement are highly sensitive but poorly specific to hepatobiliary disease.
Raised in hepatobiliary disease, alcohol, pancreatic disease, MI, COPD, renal failure, diabetes, obesity, drugs (phenytoin, barbiturates).
The reported sensitivity of a raised GGT for detecting alcohol ingestion has ranged from 52% to 94%. MCV can also be useful.

Question 39

LFT interpretation

Answer 39

Hepatic cells
ALT, coagulation factors, albumin (chronic), prothrombin time (acute).
Biliary tract
ALP, bilirubin, gamma-GT.
Hepatocellular damage
↑↑ ALT with small increase in ALP. Often chronic disease.
Hepatitis
Huge ALT values.
Biliary obstruction
Small increase in ALT with ↑↑ ALP and gamma-GT. Acute RUQ pain (possibly colicky), dark urine (bile in urine), pale stools.
Alcoholic
Very high gamma-GT (unreliable), and high MCV.

Question 40

INR/PT

Answer 40

INR / Prothrombin Time (PT)
Reference range:
PT: 10 – 14 seconds.
INR: 0.9 – 1.2
Role
PT and INR (international normalized ratio) are ways of measuring the extrinsic (factor VII) and common pathways (factor X, V, prothrombin and fibrinogen).
The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body, which has a short half-life (5-36 hours) and requires vitamin K for synthesis.
↑PT in acute liver damage (unlike albumin). Vitamin K bolus distinguishes between vitamin K or liver cause.
“WEPT”: Warfarin, Extrinsic pathway, PT (PT or INR).
↑ INR / PT
Aetiology
Deficiencies in vitamin K (warfarin, malabsorption, lack of intestinal colonization by bacteria (newborns, antibiotics).
Reduced factor VII synthesis (liver disease).
Increased consumption (DIC).
Management
INR < 6: reduce warfarin, restart when falling below 5.
INR > 8: stop warfarin, restart when falling below 5. If other risk factors for bleeding give 0.5-2.5mg vitamin K PO.
Major bleeding: stop warfarin, give FFP and 5mg vitamin K IV.

Question 41

APTT

Answer 41

Reference range: 30 – 45 seconds.
Role
The activated partial thromboplastin time (APTT, 30-45 seconds) measures the intrinsic (aka contact activation pathway; factors VIII, IX, XI, XII) and common pathways (factors X, V, prothrombin and fibrinogen).
↑ APTT
Heparin.
Haemophilia (factor VIII deficiency).
Deficiency of any of the involved factors.
Antiphospholipid antibody syndrome (common in lupus).

Question 42

GFR

Answer 42

Reference range
CKD classification (1-5) based on GFR:
1. >90 ml/min/1.73m2 with evidence of chronic kidney damage.
2. 60-89 with evidence of chronic kidney damage.
3. 30-59
4. 15-29
5. <15 (“established renal failure”).
Evidence of chronic kidney disease:
Persistent microalbuminuria
Persistent proteinuria
Persistent haematuria (after exclusion of other diseases)
Structural abnormalities of kidneys on imaging
Biopsy-proven chronic glomerulonephritis
Creatinine clearance (CrCl)
Surrogate marker for GFR.
Cockcroft and Gault formula (on iPhone). Most drug dosage calculation adjustments based on this calculation.
CrCl = (♂ 1.23, ♀ 1.04) x (140 – age) x weight in Kgs
Serum creatinine in µmol/L

Question 43

ABG

Answer 43

Aetiology of Acidosis / Alkalosis
Respiratory acidosis: CNS depression (e.g., sedatives), neuromuscular disease (Guillain-Barr, myasthenia gravis), trauma, severe restrictive disorders (scoliosis), COPD, acute airway obstruction (choking), CVA, pneumothorax, chest wall disorder, tumour.
Respiratory alkalosis: CNS disorders or lesions, hypoxia (asthma, pneumonia, pulmonary edema, PE), pulmonary vascular disease, anxiety, fear, pain, drugs (ASA, theophylline), liver failure, sepsis.
Metabolic acidosis: ketoacidosis (diabetes, chronic alcoholism, malnutrition, fasting), lactic acidosis, renal failure, toxins metabolized to acids (e.g., salicylates), toxins causing lactic acidosis (CO2, cyanide, iron), GI base loss (diarrhea, ileostomy, colostomy, enteric fistulas), renal base loss (tubulointerstitial renal disease, renal tubular acidosis, hyperparathyroidism), hypoaldosteronism, hyperkalemia, rapid NaCl infusion, severe shock (sepsis).
Metabolic alkalosis: severe vomiting (loss of H+), diuretics, NG suction, corticosteroids, hypokalaemia.
Definitions
CO2 + H2O ↔ H2CO3 (carbonic acid) ↔ H+ + HCO3- (bicarbonate)
Hypercapnia: ↑Pco2.
Type 1 Respiratory failure: PaO2 <8 kPa on air.
Type 2 Respiratory failure: PaCO2 >6.5 kPa.
Po2: reflects lung perfusion.
Pco2: reflects lung ventilation.
Hypoxaemia: Fio2 > 10kPa more than Pao2.
Reference Ranges
pH: 7.35 – 7.45
Pco2: 4.7 – 6.0 kPa
Bicarbonate (HCO3-): 22 – 28 mmol/L
Po2 (dissolved O2 in blood): 10.6 – 13 kPa on air (Fio2 = 21%)
Investigations
ABG
1: pH: is this acidosis or alkalosis?
2: Respiratory, metabolic or mixed?
3: Compensated?
Respiratory Metabolic Mixed (rare)
Acidosis  Pco2  HCO3-  Pco2  HCO3-
Compensated  HCO3-  Pco2
Alkalosis  Pco2  HCO3-
Compensated  HCO3-  Pco2