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'''Original Editor '''- [[User:John mitchell|John Mitchell ]]  
'''Original Editor '''- [[User:John mitchell|John Mitchell ]]  


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== An Introduction To Pathology  ==
== An Introduction To Pathology  ==

Revision as of 15:45, 14 June 2013

Original Editor - John Mitchell

Lead Editors - Your name will be added here if you are a lead editor on this page. 

An Introduction To Pathology[edit | edit source]

Pathology
Biochemistry
Haematology (blood bank)
Microbiology
Histology
Cytology
Immunology

Use of Pathology Tests[edit | edit source]

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

Interpretation[edit | edit source]

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

Factors affecting results[edit | edit source]

Age
Sex
Pregnancy
Posture
Exercise
Stress
Nutritional state
Time
Other medical intervention

Chemical Pathology[edit | edit source]

NB reference ranges apply to adults only and are laboratory specific and not applicable to every lab result

Water and sodium[edit | edit source]

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[edit | edit source]

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 [edit | edit source]

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
[edit | edit source]

-non specific
-have a specific time window of elevation

Alkaline phosphatase[edit | edit source]

alk: 30-120 IU/l

↑ - Pagets, osteomalacia, bone tumours, healing #, osteomyelitis.
Cholestasis, cirrhosis, hepatitis, liver tumour.

Alanine transaminase
[edit | edit source]

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[edit | edit source]

γGT/GTP: ♂<65 ♀<55 IU/l

↑ Liver disease esp. Cholestasis, alcoholic liver disease, cirrhosis, hepatitis

Amylase[edit | edit source]

Amy: <100 IU/l

↑ Acute pancreatitis
other abdo disorders, RF

Thyroid diseases
[edit | edit source]

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 Function Testing:

TSH 0.3-5mU/l

>15mU/l - 1° hypothyroidism

0.3-5mU/l - euthyroid (normal)

<0.3mU/l - Further investigations!

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

Glucose:[edit | edit source]

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[edit | edit source]

<2.0 mmol/l

↑ mainly due to tissue hypoxia (decreased perfusion or decr. PO2)

Albumin[edit | edit source]

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[edit | edit source]

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[edit | edit source]

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
[edit | edit source]

-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[edit | edit source]

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[edit | edit source]

AFP <9 KU/l

-Monitoring/detecting liver cancers, testicular cancer.
-Also raised in pregnancy, hepatic regeneration.

Human Chorionic Gonadotrophin[edit | edit source]

βHCG <5IU/l

-Diagnosis and monitoring of choriocarcinoma, also testicular tumours.
-Also used to detect ectopic pregnancies.

Prosate Specific Antigen (PSA)
[edit | edit source]

-Monitoring/detecting prostate cancer
-May be raised in benign prostatic hypertrophy

CA 125[edit | edit source]

<35 IU/l

-96% of patients with ovarian cancer have raised levels

CA 19-9[edit | edit source]

<60 IU/l

-Elevated in patients with pancreatic tumours

CA15-3
[edit | edit source]

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

Paraproteins
[edit | edit source]

-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
[edit | edit source]

Anti-nuclear antibody (ANA)[edit | edit source]

Associated with “connective tissue disease” positive in 95% of SLE, also found in JCA, Sjogren’s syndrome, fibrosing alveolitis

Anti-mitochondrial antibodies (AMA)
[edit | edit source]

positive in >95% of primary biliary cirrhosis.

Anti-smooth muscle antibodies (ASMA)
[edit | edit source]

Positive in 50-70% of autoimmune “lupoid” hepatitis

Rheumatoid factor (RF)
[edit | edit source]

(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)

Anti-Reticulin Antibodies.
[edit | edit source]

-Present in Coeliac disease. Also Crohns and UC.

Anti-acetylcholine receptor antibody
[edit | edit source]

Positive in 80-95% MG

Anti-cardiolipin antibody
[edit | edit source]

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

Anti-dsDNA antibody
[edit | edit source]

Strongly suggestive of SLE

Anti-ENA (extractable nuclear antigen) Antibody
[edit | edit source]

Used to classify connective tissue diseases

Anti-Intrinsic Factor antibody
[edit | edit source]

Positive in 70% of pernicious anaemia

Anti-neutrophil cytoplasmic antibody (ANCA)
[edit | edit source]

Wegener’s granulomatosis, microsopic arteritis

Anti-thyroid antibody
[edit | edit source]

95% positive in Hashimotos thyroiditis
90% positive in primary myxoedema
18% positive in Graves disease

Haematology
[edit | edit source]

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

Heparin
[edit | edit source]

Therapeutic administration
-DVT, PE
-MI, Unstable Angina

Prophylactic administration

->30 mins GA with post-op bed rest.
-High risk patients.

Pregnancy - Relevant side effects

-Haemorrhage
-Thrombocytopaenia

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
[edit | edit source]

-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)
[edit | edit source]

Red blood cell count (RBC)[edit | edit source]

♂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)[edit | edit source]

♂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)
[edit | edit source]

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)[edit | edit source]

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.

Recent Related Research (from Pubmed)[edit | edit source]

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References[edit | edit source]