Laboratory Tests

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An Introduction To Pathology

Pathology
Biochemistry
Haematology (blood bank)
Microbiology
Histology
Cytology
Immunology

Use of Pathology Tests
Diagnosis: to confirm or refute
Prognosis: risk factors
Monitoring: progress & treatment
Screening: subclinical presence of pathology

Interpretation
Is it normal?
Is it different?
Is it consistent with clinical findings?

Factors affecting results
Age
Sex
Pregnancy
Posture
Exercise
Stress
Nutritional state
Time
Other medical intervention
Chemical Pathology
NB reference ranges apply to adults only

Water and sodium Na: 135-145 mmol/l
↓Na (from skin, kidneys, gut) – weakness, postural hypotension, syncope, wt loss, cv changes, decreased skin turgor.
↑Na (incr. intake, decr. Excretion) – oedema, pulmonary oedema, HT, effusions

Potassium K: 3.4-5.2 mmol/l
↓K (alkalosis, RF, D&V,diuretics) – Weakness, ileus, hypotonia, confusion, depression, arrhythmias, alkalosis.
↑K (catabolism, acidosis, RF) – Cardiac arrest with VF.

Renal Function Tests
Urea & creatinine U: 2.5-6.5 mmol/l Cr: 60-120μmol/l
Both should rise together in renal failure. Creat is the more accurate measurement, urea is affected more by diet and dehydration.
Creatinine Clearance Crcl: 100-120mls/min
Measures glomerular filtration rate and permeability

Enzymes
-non specific
-have a specific time window of elevation

Alkaline phosphatase alk: 30-120 IU/l
↑ - Pagets, osteomalacia, bone tumours, healing #, osteomyelitis.
Cholestasis, cirrhosis, hepatitis, liver tumour.

Alanine transaminase Alt/GPT: <40 IU/l
↑ - Acute and chronic hepatitis, liver necrosis, tissue hypoxaemia and crush injuries, cholestasis & other liver diseases.

Creatine kinase CK: ♂40-215 ♀40-185 IU/l
↑ - MI, rhabdomyolisis, Sk. Muscle trauma, MD, severe exercise

Enzymes and MIs
-Troponin T (Trop T) rises within hours & remains elevated for days. Results reported as neg, pos or some myocardial damage.

-CK:
At 3hrs, 25% of MIs have raised CKs
At 6hrs, 72% “ “ “ “ “
At 9hrs, 97% “ “ “ “ “

Gamma glutamyl tranferase γGT/GTP: ♂<65 ♀<55 IU/l
↑ Liver disease esp. Cholestasis, alcoholic liver disease, cirrhosis, hepatitis

Amylase Amy: <100 IU/l
↑ Acute pancreatitis
other abdo disorders, RF

Thyroid diseases
Hyperthyroidism (Graves disease, multinodular goitre, adenoma) – weight loss, sweating, palpitation, angina, tremor, diarrhea, muscle weakness, goitre, eyelid retraction.
Hypothyroidism (Hashimotos disease, post surgery, congenital, secondary to pituitary/hypothalamic disease)
- lethargy, cold intolerance, dry coarse skin & hair, hoarseness, wt gain, slow reflexes & muscle relaxation. Others including: anaemia, psychosis, constipation bradycardia, CTS, infertility.

Thyroid stimulating hormone (TSH) 0.3-0.5 mU/l
Thyroid Function Testing:

TSH

>15mU/l 0.3-5mU/l <0.3mU/l
1° hypothyroidism euthyroid Further
(normal) investigations!

Interpretation complicated by:
-Many medications, hormones
-Any acute illness – “sick euthyroidism” all thyroid tests are low.
-Recovery – TSH raised.

Glucose:
Fasting 3-5.5 mmol/l
>7.8 – diagnostic of DM
5.5-7.8 – impaired glucose tolerance

Hyperglycaemia
Thirst, polyuria, dehydration, hypotension, tachycardia, drowsiness.
(and for IDDM, DKA) ketosis, hyperventilation, vomiting.

Hypoglycaemia
Tiredness, confusion, detachment, ataxia, blurred vision, dizziness, paraesthesia, hemiparesis, convulsions, coma

Lactate <2.0 mmol/l
↑ mainly due to tissue hypoxia (decreased perfusion or decr. PO2)

Proteins
Albumin alb: 36-50 g/l
– Maintains oncotic pressure (keeps fluid in vessels)
- Transports small drugs, calcium & hormones
↓ (Many causes incl. malnutrition, liver disease, overhydration, incr. cap. Permeability, protein losing states, burns, haemorrhage, general catabolism-sepsis, fever, malignancy, trauma)
Symptoms – oedema! (Unresponsive to diuretics or elevation)

C-reactive protein CRP: <5mg/l
An ‘acute phase’ protein
-Monitoring infections (>100, more likely to be bacterial)
-Distinguishing between AI diseases and active infection
-Monitoring RA Rx
-Checking for post-op infection
More sensitive than ESR

Uric acid/Urate 0.1-0.4 mmol/l
Incr. production/decr. Excretion → gout (exquisite pain and inflammation often in 1st MTP joint)
>0.54 mM → 50% chance of developing gout

Tumour Markers
-Chemicals related to the presence/progress of a tumour
-Either secreted by tumours or cell surface antigens
-Of greater prognostic than diagnostic use, should always be interpreted in the light of clinical and other diagnostic findings.

Carcinoembryonic Antigen (CEA) (2-5μg/l)
-Monitoring/detection of colorectal, gastric, breast, bronchial, bronchial and some ovarian cancers.
-Modestly elevated levels in a variety of non-malignancies

Alpha Fetoprotein (AFP) (<9 KU/l)
-Monitoring/detecting liver cancers, testicular cancer.
-Also raised in pregnancy, hepatic regeneration.

Human Chorionic Gonadotrophin (βHCG) (<5IU/l)
-Diagnosis and monitoring of choriocarcinoma, also testicular tumours.
-Also used to detect ectopic pregnancies.

Prosate Specific Antigen (PSA)
-Monitoring/detecting prostate cancer
-May be raised in benign prostatic hypertrophy

CA 125 (<35 IU/l)
-96% of patients with ovarian cancer have raised levels

CA 19-9 (<60 IU/l)
-Elevated in patients with pancreatic tumours

CA15-3
-Elevated in 70% of patients with metastatic breast cancer. A good marker for monitoring Rx.

Paraproteins
-Elevated in 98% of patients with myeloma (and other malignancies of B-cells.
-Myeloma is a haematological malignancy the symptoms of which are anaemia, bone pain (esp LBP) and pathological #s.

Immunology
Auto-immune profile:
1. Anti-nuclear antibody (ANA)
Associated with “connective tissue disease” positive in 95% of SLE, also found in JCA, Sjogren’s syndrome, fibrosing alveolitis

2. Anti-mitochondrial antibodies (AMA)
positive in >95% of primary biliary cirrhosis.

3. Anti-smooth muscle antibodies (ASMA)
Positive in 50-70% of autoimmune “lupoid” hepatitis

4. Rheumatoid factor (RF)
(anti-IgG antibodies) Positive in 70% of RA (but lots of false positives). Should only be used to screen, NOT monitor, (use C-RP instead)

5. Anti-Reticulin Antibodies.
-Present in Coeliac disease. Also Crohns and UC.

Others:
Anti-acetylcholine receptor antibody
Positive in 80-95% MG

Anti-cardiolipin antibody
Anti-phospholipid syndrome (recurrent abortion, thromboses, thrombocytopaenia)

Anti-dsDNA antibody
Strongly suggestive of SLE

Anti-ENA (extractable nuclear antigen) Antibody
Used to classify connective tissue diseases

Anti-Intrinsic Factor antibody
Positive in 70% of pernicious anaemia

Anti-neutrophil cytoplasmic antibody (ANCA)
Wegener’s granulomatosis, microsopic arteritis

Anti-thyroid antibody
95% positive in Hashimotos thyroiditis
90% positive in primary myxoedema
18% positive in Graves disease

Haematology
Coagulation studies
-Measure the clotting mechanisms, for diagnosis and extent of disorder.

The use of heparin
Therapeutic administration
-DVT, PE
-MI, Unstable Angina
-Acute peripheral occlusion.
Prophylactic administration
->30 mins GA with post-op bed rest.
-High risk patients.

Pregnancy
-The anticoagulant of choice for women requiring anticoagulation
Relevant side effects
-Haemorrhage
-Thrombocytopaenia
-Osteoporosis
Monitoring of Heparin
Low dose subcut. –
no laboratory control required
Continuous iv infusion or full dose subcut. –
APTT (activated partial thromboplastin time) should
be between 50-75 seconds. Caution with high values
(>100) re spontaneous bleeding.

Warfarin
-Patients require close monitoring of INR (International Normalized Ratio).
-Target INR ranges are 2-3 for moderate anticoagulation and 3-4.5 for more intensive therapy.
-These doses may fluctuate with no clinical significance.
-Warfarin requirements may be dramatically changed by:
illness
change in diet
change in other medication
International normalized ratio (INR)
>10 Life threatening haemorrhage can occur.
>4.5 Caution re spontaneous bleeding
-Always be wary of patients with mild haemorrhage such as haematuria or epistaxis (nosebleed).

Full Blood Count (FBC)
Red blood cell count (RBC) ♂4.5-6.5 ♀3.5-5.8
↓anaemias, Hodgkins disease, myeloma, leukaemia, haemorrhage, SLE, rheumatic fever and chronic infection.
↑polycythaemia, renal disorders, decr. plasma vol: (severe burns, shock, vomiting)
Haemoglobin (Hb) ♂13-18 ♀12-16
↓anaemia, hyperthyroidism, liver/kidney disease, many CAs (especially haematological) SLE
↑haemoconcentration disorders: burns, polycythaemia, COPD, CCF.
<5 can lead to MI
>20 can lead to clogging of capillaries.
White blood cell count (WBC) A useful guide to the severity of a disease process
Neutrophils 2.5-7.5
Lymphocytes 1-3.5
Monocytes 0.2-0.8
Eosinophils 0.04-0.4
Basophils 0.01-0.1

Neutrophilia(↑) bacterial infections, gout, uraemia, poisoning, haemorrhage, haemolysis, necrosis.
Neutropaenia(↓) bacterial infections (poor prognosis) viral infections, certain anaemias, blood cancers, anaphylactic shock.
Eosinophilia(↑) Allergic reactions, parasitic diseases, certain blood cancers, skin infections, immunodeficiency disorders.
-Other variations occur in the specific white blood cell differential count with conditions such as: anaemias, blood cancers, infections, and certain inflammatory disorders.

Platelets (150-400)
Thrombocytosis(↑) malignancies, polycythaemia, RA & other inflammatory diseases, acute infections,
Thrombocytopaenia(↓) toxic affects of drugs, esp. chemotherapy, allergies, anaemias, viral infections, post transfusion, ITP.
Caution with low values re spontaneous bleeding, and bruising.