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An Introduction To Pathology
 
Pathology<br>Biochemistry<br>Haematology (blood bank)<br>Microbiology <br>Histology<br>Cytology<br>Immunology
 
Use of Pathology Tests<br>Diagnosis: to confirm or refute<br>Prognosis: risk factors<br>Monitoring: progress &amp; treatment<br>Screening: subclinical presence of pathology
 
Interpretation<br>Is it normal?<br>Is it different?<br>Is it consistent with clinical findings?
 
Factors affecting results<br>Age<br>Sex<br>Pregnancy<br>Posture<br>Exercise<br>Stress<br>Nutritional state<br>Time<br>Other medical intervention<br>Chemical Pathology<br>NB reference ranges apply to adults only
 
Water and sodium Na: 135-145 mmol/l<br>↓Na (from skin, kidneys, gut) – weakness, postural hypotension, syncope, wt loss, cv changes, decreased skin turgor. <br>↑Na (incr. intake, decr. Excretion) – oedema, pulmonary oedema, HT, effusions
 
Potassium K: 3.4-5.2 mmol/l<br>↓K (alkalosis, RF, D&amp;V,diuretics) – Weakness, ileus, hypotonia, confusion, depression, arrhythmias, alkalosis.<br>↑K (catabolism, acidosis, RF) – Cardiac arrest with VF.
 
Renal Function Tests<br>Urea &amp; creatinine U: 2.5-6.5 mmol/l Cr: 60-120μmol/l<br>Both should rise together in renal failure. Creat is the more accurate measurement, urea is affected more by diet and dehydration.<br>Creatinine Clearance Crcl: 100-120mls/min<br>Measures glomerular filtration rate and permeability
 
Enzymes<br>-non specific<br>-have a specific time window of elevation
 
 
 
 
 
Alkaline phosphatase alk: 30-120 IU/l<br>↑ - Pagets, osteomalacia, bone tumours, healing #, osteomyelitis.<br>Cholestasis, cirrhosis, hepatitis, liver tumour.
 
Alanine transaminase Alt/GPT: &lt;40 IU/l<br>↑ - Acute and chronic hepatitis, liver necrosis, tissue hypoxaemia and crush injuries, cholestasis &amp; other liver diseases.
 
Creatine kinase CK: ♂40-215 ♀40-185 IU/l<br>↑ - MI, rhabdomyolisis, Sk. Muscle trauma, MD, severe exercise
 
Enzymes and MIs<br>-Troponin T (Trop T) rises within hours &amp; remains elevated for days. Results reported as neg, pos or some myocardial damage.
 
-CK:<br>At 3hrs, 25% of MIs have raised CKs<br>At 6hrs, 72% “ “ “ “ “<br>At 9hrs, 97% “ “ “ “ “
 
Gamma glutamyl tranferase γGT/GTP: ♂&lt;65 ♀&lt;55 IU/l<br>↑ Liver disease esp. Cholestasis, alcoholic liver disease, cirrhosis, hepatitis
 
Amylase Amy: &lt;100 IU/l<br>↑ Acute pancreatitis<br>other abdo disorders, RF
 
Thyroid diseases<br>Hyperthyroidism (Graves disease, multinodular goitre, adenoma) – weight loss, sweating, palpitation, angina, tremor, diarrhea, muscle weakness, goitre, eyelid retraction.<br>Hypothyroidism (Hashimotos disease, post surgery, congenital, secondary to pituitary/hypothalamic disease)<br>- lethargy, cold intolerance, dry coarse skin &amp; hair, hoarseness, wt gain, slow reflexes &amp; muscle relaxation. Others including: anaemia, psychosis, constipation bradycardia, CTS, infertility.
 
Thyroid stimulating hormone (TSH) 0.3-0.5 mU/l<br>Thyroid Function Testing:
 
TSH
 
<br>&gt;15mU/l 0.3-5mU/l &lt;0.3mU/l<br>1° hypothyroidism euthyroid Further <br> (normal) investigations!
 
Interpretation complicated by:<br>-Many medications, hormones<br>-Any acute illness – “sick euthyroidism” all thyroid tests are low.<br>-Recovery – TSH raised.
 
 
 
<br>Glucose:<br>Fasting 3-5.5 mmol/l <br> &gt;7.8 – diagnostic of DM<br> 5.5-7.8 – impaired glucose tolerance
 
Hyperglycaemia<br>Thirst, polyuria, dehydration, hypotension, tachycardia, drowsiness.<br>(and for IDDM, DKA) ketosis, hyperventilation, vomiting.
 
Hypoglycaemia<br>Tiredness, confusion, detachment, ataxia, blurred vision, dizziness, paraesthesia, hemiparesis, convulsions, coma
 
Lactate &lt;2.0 mmol/l<br>↑ mainly due to tissue hypoxia (decreased perfusion or decr. PO2)
 
Proteins<br>Albumin alb: 36-50 g/l<br>– Maintains oncotic pressure (keeps fluid in vessels)<br>- Transports small drugs, calcium &amp; hormones<br>↓ (Many causes incl. malnutrition, liver disease, overhydration, incr. cap. Permeability, protein losing states, burns, haemorrhage, general catabolism-sepsis, fever, malignancy, trauma)<br>Symptoms – oedema! (Unresponsive to diuretics or elevation)
 
 
 
C-reactive protein CRP: &lt;5mg/l<br>An ‘acute phase’ protein <br>-Monitoring infections (&gt;100, more likely to be bacterial)<br>-Distinguishing between AI diseases and active infection<br>-Monitoring RA Rx<br>-Checking for post-op infection <br>More sensitive than ESR<br> <br>Uric acid/Urate 0.1-0.4 mmol/l<br>Incr. production/decr. Excretion → gout (exquisite pain and inflammation often in 1st MTP joint)<br>&gt;0.54 mM → 50% chance of developing gout
 
Tumour Markers<br>-Chemicals related to the presence/progress of a tumour<br>-Either secreted by tumours or cell surface antigens<br>-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)<br>-Monitoring/detection of colorectal, gastric, breast, bronchial, bronchial and some ovarian cancers.<br>-Modestly elevated levels in a variety of non-malignancies
 
Alpha Fetoprotein (AFP) (&lt;9 KU/l)<br>-Monitoring/detecting liver cancers, testicular cancer.<br>-Also raised in pregnancy, hepatic regeneration.
 
 
 
Human Chorionic Gonadotrophin (βHCG) (&lt;5IU/l)<br>-Diagnosis and monitoring of choriocarcinoma, also testicular tumours.<br>-Also used to detect ectopic pregnancies.
 
Prosate Specific Antigen (PSA) <br>-Monitoring/detecting prostate cancer<br>-May be raised in benign prostatic hypertrophy
 
CA 125 (&lt;35 IU/l)<br>-96% of patients with ovarian cancer have raised levels
 
CA 19-9 (&lt;60 IU/l)<br>-Elevated in patients with pancreatic tumours
 
CA15-3<br>-Elevated in 70% of patients with metastatic breast cancer. A good marker for monitoring Rx.
 
Paraproteins<br>-Elevated in 98% of patients with myeloma (and other malignancies of B-cells.<br>-Myeloma is a haematological malignancy the symptoms of which are anaemia, bone pain (esp LBP) and pathological #s.
 
 
 
 
 
Immunology<br>Auto-immune profile:<br>1. Anti-nuclear antibody (ANA)<br>Associated with “connective tissue disease” positive in 95% of SLE, also found in JCA, Sjogren’s syndrome, fibrosing alveolitis
 
2. Anti-mitochondrial antibodies (AMA)<br>positive in &gt;95% of primary biliary cirrhosis.<br> <br>3. Anti-smooth muscle antibodies (ASMA)<br>Positive in 50-70% of autoimmune “lupoid” hepatitis
 
4. Rheumatoid factor (RF)<br>(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.<br>-Present in Coeliac disease. Also Crohns and UC.
 
Others:<br>Anti-acetylcholine receptor antibody <br>Positive in 80-95% MG
 
Anti-cardiolipin antibody<br>Anti-phospholipid syndrome (recurrent abortion, thromboses, thrombocytopaenia)
 
Anti-dsDNA antibody<br>Strongly suggestive of SLE
 
Anti-ENA (extractable nuclear antigen) Antibody<br>Used to classify connective tissue diseases
 
Anti-Intrinsic Factor antibody<br>Positive in 70% of pernicious anaemia
 
Anti-neutrophil cytoplasmic antibody (ANCA)<br>Wegener’s granulomatosis, microsopic arteritis
 
Anti-thyroid antibody<br>95% positive in Hashimotos thyroiditis<br>90% positive in primary myxoedema<br>18% positive in Graves disease
 
 
 
 
 
 
 
 
 
 
 
 
 
<br>Haematology<br>Coagulation studies<br>-Measure the clotting mechanisms, for diagnosis and extent of disorder.
 
The use of heparin<br>Therapeutic administration<br>-DVT, PE<br>-MI, Unstable Angina<br>-Acute peripheral occlusion.<br>Prophylactic administration<br>-&gt;30 mins GA with post-op bed rest.<br>-High risk patients.
 
<br>Pregnancy<br>-The anticoagulant of choice for women requiring anticoagulation<br>Relevant side effects<br>-Haemorrhage<br>-Thrombocytopaenia<br>-Osteoporosis<br>Monitoring of Heparin<br>Low dose subcut. – <br>no laboratory control required<br>Continuous iv infusion or full dose subcut. – <br> APTT (activated partial thromboplastin time) should <br> be between 50-75 seconds. Caution with high values <br> (&gt;100) re spontaneous bleeding.
 
 
 
Warfarin<br>-Patients require close monitoring of INR (International Normalized Ratio).<br>-Target INR ranges are 2-3 for moderate anticoagulation and 3-4.5 for more intensive therapy.<br>-These doses may fluctuate with no clinical significance.<br>-Warfarin requirements may be dramatically changed by:<br>illness<br>change in diet<br>change in other medication<br>International normalized ratio (INR) <br>&gt;10 Life threatening haemorrhage can occur.<br>&gt;4.5 Caution re spontaneous bleeding<br>-Always be wary of patients with mild haemorrhage such as haematuria or epistaxis (nosebleed).
 
<br>Full Blood Count (FBC)<br>Red blood cell count (RBC) ♂4.5-6.5 ♀3.5-5.8 <br>↓anaemias, Hodgkins disease, myeloma, leukaemia, haemorrhage, SLE, rheumatic fever and chronic infection.<br>↑polycythaemia, renal disorders, decr. plasma vol: (severe burns, shock, vomiting)<br>Haemoglobin (Hb) ♂13-18 ♀12-16<br>↓anaemia, hyperthyroidism, liver/kidney disease, many CAs (especially haematological) SLE<br>↑haemoconcentration disorders: burns, polycythaemia, COPD, CCF.<br>&lt;5 can lead to MI<br>&gt;20 can lead to clogging of capillaries.<br>White blood cell count (WBC) A useful guide to the severity of a disease process<br>Neutrophils 2.5-7.5<br>Lymphocytes 1-3.5<br>Monocytes 0.2-0.8<br>Eosinophils 0.04-0.4<br>Basophils 0.01-0.1
 
Neutrophilia(↑) bacterial infections, gout, uraemia, poisoning, haemorrhage, haemolysis, necrosis.<br>Neutropaenia(↓) bacterial infections (poor prognosis) viral infections, certain anaemias, blood cancers, anaphylactic shock.<br>Eosinophilia(↑) Allergic reactions, parasitic diseases, certain blood cancers, skin infections, immunodeficiency disorders.<br>-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)<br>Thrombocytosis(↑) malignancies, polycythaemia, RA &amp; other inflammatory diseases, acute infections, <br>Thrombocytopaenia(↓) toxic affects of drugs, esp. chemotherapy, allergies, anaemias, viral infections, post transfusion, ITP.<br>Caution with low values re spontaneous bleeding, and bruising.<br><br>

Latest revision as of 17:55, 28 May 2021

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