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


Pathology<br>Biochemistry<br>Haematology (blood bank)<br>Microbiology <br>Histology<br>Cytology<br>Immunology  
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
=== Use of Pathology Tests ===


Interpretation<br>Is it normal?<br>Is it different?<br>Is it consistent with clinical findings?
Diagnosis: to confirm or refute<br>Prognosis: risk factors<br>Monitoring: progress &amp; treatment<br>Screening: subclinical presence of pathology


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
==== Interpretation  ====


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
Is it normal?<br>Is it different?<br>Is it consistent with clinical findings?


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.
==== Factors affecting results  ====


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


Enzymes<br>-non specific<br>-have a specific time window of elevation
== Chemical Pathology ==


<br>
NB reference ranges apply to adults only


<br>  
==== Water and sodium Na: 135-145 mmol/l<br> ====


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


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.  
==== 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&nbsp;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 <br> ====
 
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  
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.  
==== 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


-CK:<br>At 3hrs, 25% of MIs have raised CKs<br>At 6hrs, 72% “ “ “ “ “<br>At 9hrs, 97% “ “ “ “ “
==== Amylase Amy: &lt;100 IU/l<br> ====


Gamma glutamyl tranferase γGT/GTP: ♂&lt;65 ♀&lt;55 IU/l<br>↑ Liver disease esp. Cholestasis, alcoholic liver disease, cirrhosis, hepatitis
↑ Acute pancreatitis<br>other abdo disorders, RF


Amylase Amy: &lt;100 IU/l<br>↑ Acute pancreatitis<br>other abdo disorders, RF
== Thyroid diseases<br> ==


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.  
'''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.<br>


Thyroid stimulating hormone (TSH) 0.3-0.5 mU/l<br>Thyroid Function Testing:
==== Thyroid Function Testing: TSH 0.3-5mU/l<br> ====


TSH
&gt;15mU/l - 1° hypothyroidism<br>


<br>&gt;15mU/l 0.3-5mU/l &lt;0.3mU/l<br>1° hypothyroidism euthyroid Further <br> (normal) investigations!
0.3-5mU/l - euthyroid (normal)
 
&lt;0.3mU/l - Further investigations! <br>


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


<br>  
==== Glucose: 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>
 
==== 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> ====


<br>Glucose:<br>Fasting 3-5.5 mmol/l <br> &gt;7.8 – diagnostic of DM<br> 5.5-7.8 – impaired glucose tolerance
-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.  


Hyperglycaemia<br>Thirst, polyuria, dehydration, hypotension, tachycardia, drowsiness.<br>(and for IDDM, DKA) ketosis, hyperventilation, vomiting.
== Immunology<br> ==


Hypoglycaemia<br>Tiredness, confusion, detachment, ataxia, blurred vision, dizziness, paraesthesia, hemiparesis, convulsions, coma
=== Auto-immune profile:<br> ===
Anti-nuclear antibody (ANA)<br> ====


Lactate &lt;2.0 mmol/l<br>↑ mainly due to tissue hypoxia (decreased perfusion or decr. PO2)
Associated with “connective tissue disease” positive in 95% of SLE, also found in JCA, Sjogren’s syndrome, fibrosing alveolitis<br>


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)
==== Anti-mitochondrial antibodies (AMA)<br> ====


<br>  
positive in &gt;95% of primary biliary cirrhosis.<br>


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
==== Anti-smooth muscle antibodies (ASMA)<br> ====


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.
Positive in 50-70% of autoimmune “lupoid” hepatitis<br>


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
==== Rheumatoid factor (RF)<br> ====


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


<br>  
==== Anti-Reticulin Antibodies.<br> ====
-Present in Coeliac disease. Also Crohns and UC.


Human Chorionic Gonadotrophin (βHCG) (&lt;5IU/l)<br>-Diagnosis and monitoring of choriocarcinoma, also testicular tumours.<br>-Also used to detect ectopic pregnancies.
=== Others:<br> ===


Prosate Specific Antigen (PSA) <br>-Monitoring/detecting prostate cancer<br>-May be raised in benign prostatic hypertrophy
==== Anti-acetylcholine receptor antibody <br> ====


CA 125 (&lt;35 IU/l)<br>-96% of patients with ovarian cancer have raised levels
Positive in 80-95% MG


CA 19-9 (&lt;60 IU/l)<br>-Elevated in patients with pancreatic tumours
==== Anti-cardiolipin antibody<br> ====


CA15-3<br>-Elevated in 70% of patients with metastatic breast cancer. A good marker for monitoring Rx.
Anti-phospholipid syndrome (recurrent abortion, thromboses, thrombocytopaenia)


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.
==== Anti-dsDNA antibody<br> ====


<br>
Strongly suggestive of SLE


<br>  
==== Anti-ENA (extractable nuclear antigen) Antibody<br> ====


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
Used to classify connective tissue diseases


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
==== Anti-Intrinsic Factor antibody<br> ====


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)
Positive in 70% of pernicious anaemia


5. Anti-Reticulin Antibodies.<br>-Present in Coeliac disease. Also Crohns and UC.
==== Anti-neutrophil cytoplasmic antibody (ANCA)<br> ====


Others:<br>Anti-acetylcholine receptor antibody <br>Positive in 80-95% MG
Wegener’s granulomatosis, microsopic arteritis


Anti-cardiolipin antibody<br>Anti-phospholipid syndrome (recurrent abortion, thromboses, thrombocytopaenia)
==== Anti-thyroid antibody<br> ====


Anti-dsDNA antibody<br>Strongly suggestive of SLE
95% positive in Hashimotos thyroiditis<br>90% positive in primary myxoedema<br>18% positive in Graves disease<br>


Anti-ENA (extractable nuclear antigen) Antibody<br>Used to classify connective tissue diseases
== Haematology<br> ==


Anti-Intrinsic Factor antibody<br>Positive in 70% of pernicious anaemia
Coagulation studies -Measure the clotting mechanisms, for diagnosis and extent of disorder.


Anti-neutrophil cytoplasmic antibody (ANCA)<br>Wegener’s granulomatosis, microsopic arteritis
==== Heparin<br> ====


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


<br>  
'''Pregnancy'''<br>


<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.


<br>  
==== Warfarin<br> ====


<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>


<br>  
==== Full Blood Count (FBC)<br> ====


<br>  
===== Red blood cell count (RBC) ♂4.5-6.5 ♀3.5-5.8 <br> =====


<br>Haematology<br>Coagulation studies<br>-Measure the clotting mechanisms, for diagnosis and extent of disorder.
↓anaemias, Hodgkins disease, myeloma, leukaemia, haemorrhage, SLE, rheumatic fever and chronic infection.<br>↑polycythaemia, renal disorders, decr. plasma vol: (severe burns, shock, vomiting)<br>


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.
===== Haemoglobin (Hb) ♂13-18 ♀12-16<br> =====


<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.
↓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>


<br>  
===== White blood cell count (WBC)<br> =====


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).  
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'''


<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.  


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) =====


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>
'''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>

Revision as of 23:08, 9 March 2009

Original Editor - John Mitchell

Lead Editors - If you would like to be a lead editor on this page, please contact us.

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

Water and sodium Na: 135-145 mmol/l
[edit | edit source]

↓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
[edit | edit source]

↓K (alkalosis, RF, D&V,diuretics) – Weakness, ileus, hypotonia, confusion, depression, arrhythmias, alkalosis.
↑K (catabolism, acidosis, RF) – Cardiac arrest with VF.

Renal Function Tests
[edit | edit source]

Urea & creatinine U: 2.5-6.5 mmol/l Cr: 60-120μmol/l
[edit | edit source]

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 alk: 30-120 IU/l
[edit | edit source]

↑ - 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
[edit | edit source]

-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
[edit | edit source]

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

Amylase Amy: <100 IU/l
[edit | edit source]

↑ 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
[edit | edit source]

>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: Fasting 3-5.5 mmol/l
[edit | edit source]

>7.8 – diagnostic of DM
5.5-7.8 – impaired glucose tolerance

Hyperglycaemia
[edit | edit source]

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

Hypoglycaemia
[edit | edit source]

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

Lactate <2.0 mmol/l
[edit | edit source]

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

Proteins
[edit | edit source]

Albumin alb: 36-50 g/l
[edit | edit source]

– 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
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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
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Incr. production/decr. Excretion → gout (exquisite pain and inflammation often in 1st MTP joint)
>0.54 mM → 50% chance of developing gout

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

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

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

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

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

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

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

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

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

Rheumatoid factor (RF)
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(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.
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-Present in Coeliac disease. Also Crohns and UC.

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

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

Anti-dsDNA antibody
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Strongly suggestive of SLE

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

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

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

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

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

Heparin
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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
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-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)
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Red blood cell count (RBC) ♂4.5-6.5 ♀3.5-5.8
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↓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
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↓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)
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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.