Lab Med Mbchb4

LABORATORY MEDICINE 1: Case 1 – Rheumatic Fever

18 F Maori
Presents with – 5 day hx fever + sweats
Past Hx – RF age 9 yrs (no regular penicillin prophylaxis last 2 yrs)
O/E – mitral regurg murmur
Ix – 3x blood cultures collected over two hour period – all growing a G+ coccus

1. Probable Dx
a. Bacterial endocarditis
b. Most likely organisms – Viridans streptococci (S.sanguis, S.mitis, S.mutans), S.aureus
c. Child gets RF (GAS pharyngitis) → immunological reaction (antigen mimicry) → attack on heart valve
d. Differences betw RF and Endocarditis
i. RF
1. pharyngitis due to S.pyogenes
2. Immunological damage to heart valves
3. Serology for dx
4. Tx of pharyngitis usu penicillin PO for 10 days
5. Penicillin prophylax continuously to prevent pharngitis
ii. Endocarditis
1. oral colonisation with viridans strep
2. infected vegetation on heart valves (damaged by pre-existing damage from RF)
3. blood cultures for dx (gold standard)
4. tx of endovascular infection with penicillin IV >14 days
5. penicillin prophylaxis intermittently eg at dental work to prevent viridans strep bacteraemia
2. Ixs
a. Identification of G +ve cocci
b. Antibiotic sensitivity (from blood cultures)
c. Cardiology assessment and echo
3. Mgt (depends on sensitivities)
a. Penicillin 4 wks
b. Penicillin + Gent 2 wks
c. Fluclox 4 wks
4. How can risk of recurrence of this disease be reduced?
a. Prophylaxis at times of dental work or other causes of bacteriaemia to prevent endocarditis
b. Consider AB prophylaxis >10 yrs to prevent pharyngitis
5. Prognosis of endocarditis
a. 100% mortality untx
b. 10-30% with tx – due to complications (eg valve damage, emboli (splinter hems), aortic incompetence)

Rheumatic Fever

Def Inflam dis which may develop after a grp A strep inf (eg strep throat or scarlet fever), can involve heart, joints, skin, brain
Epidem Responsible for many cases of damaged heart valves
Primarily affects children 6-15 yrs (occurs approx 20 days after strep throat or scarlet fever) – no clinical sxs prev inf in 1/3 pts
Recurrence of RF relatively common in absence of maintenance of low dose AB (esp during first 3-5 yrs post first episode)
Heart complications may be LT and severe esp if heart valves involved
Modified Jones Criteria – support dx of RF if also evidence of previous strep inf
Major 1. Carditis (inflam of heart mus) – can manifiest as CHF with SOB, pericarditis (+ rub) or new heart murmur
2. Migratory polyarthritis – large joints
3. Sydenham’s chorea – series of rapid mvments w/o purpose of face and arms
4. Erythema marginatum – LT rash starting on trunk/arms as macules and spread outward to form a snakelike ring with clearing in the middle
5. Subcutaneous nodules (form of aschoff bodies) – painless, firm collections collagen fibers back of wrist, outside elbow, front of knees)
Minor Fever
Arthralgia – joint pain w/o swelling
Lab abnormalities – ESR ↑, CRP ↑, ↑ wcc
ECG abnormalities – prolonged PR
Evidence of group A strep inf – positive culture, elev or rising antistreptolysin O titre
Previous RF or inactive heart dis
M proteins in cell wall of S. pyogenes → similar to cardiac myofiber sarcolemma and SMCs arteries
Cross reaction → CK release → tissue destr (inflam occurs via direct complement activation and Fc R-mediated neutrophil/mphage recruit)
Inflam of endocardium typically results in fibrinoid necrosis and verrucae formation on L heart valves → leaflet thickening, fusion, shortening
RHD causes 99% of mitral stenosis → fish mouth appearance
Tx Acute RF → anti-inflam meds (aspirin, corticosterois)
Pos cultures for strep throat – AB
Chronic Tx – low dose AB to prevent recurrence
HF Some pts develop sig carditis manifesting as CHF – requires usual HF tx (diuretics, digoxin…) – responds well to corticosteroids
Prev eradicate actue inf + AB prophylaxis (>10 yrs)

Additional Notes
Pt with known valve damage undergoing dental work → always give AB prophylaxis

LABORATORY MEDICINE 1: Case 2 – Lactic Acidosis secondary to a seizure

83 M
Pres to ED – fitting (seizures have stopped – he is drowsy and confused)
No hx available yet
ABGs ph 6.8, PCO2 normal, PO2 68 (10.6-13.3), Bicarb 6 (20-27), BE -29 (-2 - +2), Na 134, glucose 15.4

1. Impt issues in collecting a blood gas specimen. Could a collection error be responsible for these changes?
a. These changes NOT likely to be solely the result of a collection problem
b. Large air bubble → high PO2 (but not higher than atmospheric 20 kPa)
c. Impt issues in BG collection are –
i. Exclude air bubble – high PO2, low PCO2
ii. Analysis soon as possible after collection (<30 mins) – minimises changes caused by continuing metab of white cells in specimen giving low PO2 and high PCO2
iii. Transport specimen in ice – slows metabolism above
iv. Mislabelling
2. Approach to ABG results
a. pH - <7.35 = acidosis, >7.45 = alkalosis
b. If acidosis - is it metabolic HCO3 <20 mmol/l or respiratory PCO2 >6 kPa
c. If alkalosis – it is metabolic HCO3 >30 mmol/l or respiratory PCO2 <4.6 kPa
d. What is the primary problem?
i. Metabolic acidosis – renal failure, ketoacidosis, lactic acidosis, diarrhea etc
ii. Respiratory acidosis – hypoventilation from drugs, neurological or respiratory dis
iii. Metabolic alkalosis – vomiting, diuretics etc
iv. Respiratory alkalosis – hyperventilation from respiratory dis, anxiety, salicylate OD etc
e. Is there appropriate compensation?
3. What are the abnormalities in this case?
a. Severe uncompensated – low pH, low bicarb, failure to compensate by ↓ PCO2 (depends on ability of lungs to hyperventilate)
b. This pattern is common soon after a generalised seizure where there is lactic acidosis from vigorous mus contractions (m.acidosis) and hypoxia due to respiratory impairment (inhalation asphyxia, central obtundation, disordered respiratory (r.acidosis)
4. How can you explain the high O2?
a. Supplemental O2 – the PO2 is greater than atmospheric PO2 (20 kPa)
5. What is the significance of low sodium and high glucose?
a. High glucose is common in stress situations in people who are not diabetics – should follow it up later anyway
b. Low sodium is a minor non-specific finding
6. How will these results help manage this patient?
a. He will come right with time (typical post-ictal response)
b. Repeat ABGs
c. Fasting glucose
d. Etiology of seizures
i. Elderly people (primary neurological problems – strokes or tumour) → CT
ii. Younger (epilepsy)
e. If the pt does not stop fitting → Diazepam IV or PR
7. When are blood gases measurements indicated and when avoided?
a. Indications
i. Assessment of resp function – pts w resp failure, breathlessness, asthma, chr airways dis
ii. Assessing acid-base status in acutely ill pts
b. Contraindications – thrombocytopenia (<100), hemophilia or other coagulation defects

LABORATORY MEDICINE 1: Case 3 – Thrombocytopenia

22 F
Pres – 2 wk hx recurrent nosebleeds + easy bruising
PMH – never unwell in past
Meds – OCP
O/E – afebrile, no lymphadenopathy, no hepatosplenomegaly, blood blisters inside mouth, petechiae over lower limbs

1. What are the main laboratory abnormalities?
a. Severe isolated thrombocytopenia – Platelet count 24 (150-400)
2. Possible causes?
a. ITP – Idiopathic thrombocytopenic purpura
i. Unknown cause - ?autoimmune
ii. Most likely here as no other abnormalities
b. Viral infections – mild thrombocytopenia (often w variant lymphocytes) can occur w viral illnesses such as GF – usu self limiting
c. Drug reactions – wide variety incl sulphonamides (trimethoprim), thiazides
d. Others – haematological malignancy, bone marrow infiltration etc (unlikely here as other counts normal and no abnormal cells in peripheral blood)
e. SLE
f. Test error – platelet clumping
3. What additional ixs?
a. Repeat FBC – to excl platelet clumping error in first test + confirm the abnormality
b. ANA – to excl SLE
c. Infectious mono screen and other viral serology
d. Bone marrow aspirate – looking for incr umbers of megakaryocytes + to excl leukaemia etc) – should be performed if diagnostic doubt, in older pts and if refractory to initial therapy and splenectomy is being considered. Not reqd for this pt yet.
4. Most likely dx in this pt? → ITP
5. How would you manage this pt?
a. Platelets >50 → sit and wait, bleeding risk low, GP mgt
b. Platelets 20-50 → haematology referral
c. Platelets <20 → admit + tx, start prednisone 1mg daily and hope for response over next few weeks
i. 95% response in children, 80% response in adults
ii. ½ the responders will relapse when steroids are stopped
d. For non-responsive or recurrent thrombocytopenia → IV gamma globulin (transiently incr platelet count) then splenectomy
e. Splenectomy is the final outcome in 20-30% of adults with ITP
f. Immunisation vs haemophilus, pneumococcus and meningococcus prror to splenectomy
6. When considering thrombocytopenia or neutropenia – consider whether it is a –
a. Production problem – eg bone marrow infiltration
b. Consumption problem – eg immune, hypersplenism

Def Low platelet count unknown cause (most autoimm) - Most cases asx (but v low counts → bleeding and purpura)
Epidem 20-30 yrs F>M 3>1 (1:1 children)
Acute (<6 months) or Chr (>1 yr)
Acute type more common in children and 80% self limiting
Chr type more common in adults and tends to get worse as the dis progresses
Sxs Petechiae, Bruising, nosebleeds, bleeding gums, subarachnoid or intracerebral hem (rare but v serious)
Spleen not enlarged (despite destruction of platelets by splenic mphages)
Overall bleeding time prolonged but PT and PPT normal (as problem w platelets not coagulation cascade)
Pathogen Often antibods against platelet membr glycoproteins, coating of platelets w IgG → opsonization + phagocytosis by splenic mphages
Dx ITP is a clinical dx reached by exclusion

LABORATORY MEDICINE TUTORIAL 2: Case 1 – Pulmonary edema and MI

88F - Develops acute pulmonary edema the night after an op
No hx chest pain, ECG unhelpful (shows pre-existing L bundle br block)

Blood Results evening of op and the following days
Day 1 (op) 2 2 2 3
Time 8pm 4am 9am 3pm 9am
Urea 18.4* 26.2* 26.7* (3.2-7.7)
Creat 150 230 240 (50-120)
CK 88 95 98 (30-180)
Trop T 0.24* (<0.10)

1. What is the role of biochemical testing in the assessment of pts with suspected MI? Adv and disadv of CK, CK-MB, Trop I/T and myoglobin
a. Biochemical tests – used to confirm a dx of MI (not usu the basis of acute tx)
b. CK (creatinine kinase) – cheap, well established, limited compared to other markers, breakdown product from cardiac injury and skeletal muscle/brain injury
c. CK-MB – relatively cardiac-specific isoform of K, rises and falls quickly after an MI, seldom used as troponins more sens/specific
d. Troponins I and T (standard of care)
i. Troponins are not normally detectable in plasma – any elev suggestive of myocardial damage
ii. 50% positive after 4-5 hrs (similar to CKMB), 99% positive after 10-12 hrs
iii. Remain elev for 4-7 days
iv. Both Trop T and I can be incr in people with RF (likely represents slow myocardial injury, high LT cardiac risk)
v. A pt with suspicious sxs but no troponin rise may still have had an ischemic event and treadmill testing and angiography may be indicated
vi. Cardiac troponins are a marker of heart mus damage (not just MI) – other conditions incl cardiac amyloidosis, cardiac contusion, cardiac surgery, defib, coronary vasospasm, dilated cardiomyopathy (stretchy), non-cardiac illnesses incl sepsis, pulmonary THN, PE< RF, v heavy exercise
e. Myoglobin – non-specific, but raised v early an MI, useful in window period before tropinins rise
2. Has this pt had a MI?
a. Unclear with this data
b. Troponin – critical test (clear troponin rise in the appropriate acute clinical setting) is diagnostic
c. However, some people with HF or CRF have chr mild elev in troponins which may reflect ongoing minor injury rather than an infarct
d. F-up troponin in 2-3 wks would be helpful
3. Suggest why levels of urea and Creatinine are increased?
a. Most likely - ↓ renal perfusion, due to cardiac failure +/- diuretic therapy for acute p.edema

Pulmonary Edema

Def swelling +/or accum fluid in lungs → impaired gas exchange and may cause respiratory failure
Pres Acute – Dyspnea, Hemoptysis, Excessive sweating, Anxiety, Pale skin
Chr – sxs of fluid overload → nocturia, pitting edema ankle, orthopnea (breathless on lying flat), paroxysmal nocturnal dyspnea
Etiol Cardiogenic p.edema – failure of the heart to remove fluid from the lung circ
Valvular dis eg mitral stenosis
Severe arrhthmias (tachycardia or bracycardia)
Pericardial effusion w tamponade
Fluid overload - RF
Noncardiogenic p.edema – direct injury to lung parenchyma (this form contiguous w ARDS – acute resp distress syndr)
Inhalation toxic gases
Severe inf
Pulmonary contusion (high energy trauma)
Multitrauma (eg mva)
Aspiration – gastric fluid or drowning
Upper airway obstruction
Ascent to high altitude (HAPE)
Dx Hx – prev CV dis
O/E – end-inspiratory crackles, S3 heart sound (cardiogenic p.edema)
Ixs Blood – electrolytes, creatinine, urea, liver enzymes, inflam markers (usu CRP), FBC, coagulation studies (PT, aPTT), BNP
Low levels BNP make cardiac cause v unlikely
XR lungs –
Cardiogenic - ↑ fluid alveolar walls (kerley b lines), ↑ vasc filling, pl.effusions, upperlobe diversion (↑ bld flow higher parts of lung)
Non-cardiogenic – patchy alveolar infiltrates w air brocnhograms
↓ O2 sat and disturbed ABG
Echo – may strengthen dx and identify valvular heart dis
Tx Maximise resp func – maintain adequate oxygenation (high flow O2, non-invasive vent (CPAP or VPAP – variable + airway pres)), mech vent
If circ cause → IV Nitrates (GTN) + Loop diuretics (furosemide) → improve preload and afterload improving cardiac func
If inf → tx
Prog W/o tx – can lead to coma or death (due to hypoxia)


12 F
PC - pain + swelling R knee + L ankle
Temp 38’

Streptococcal Serology Results
ASOT 325 IU (0-75)
Anti DNase B 680 (0-75)
CRP 54 mg/l (0-8)

1. What is the differential dx of fever and arthritis like this in a 12 yr old girl?
a. Septic arthritis (unlikely as 2x joints)
b. Acute rheumatic fever
c. Reactive arthritis
d. CT disease
2. What do the serological results suggest?
a. Anti-streptococcal titres are elevated
b. No single titre is diagnostic
c. ASOT and Anti-DNAse B – requires 2x ↑ for dx
i. ASOT = anti-streptolysin O antibody titre (exotoxin produced by grp A strep – s.pyogenes)
ii. Anti-DNAse B – antibodies against anti-DNA B (antigen produced by GAS)
d. CRP elev and consistent with arthritis (elev during acute episodes of inflammation)
3. What other clinical features should be sought?
a. Evidence of recent pharyngitis – ie throat infection
b. Cardiac murmurs
c. Less common – erythemia marginatum, subcutaneous nodules, chorea
d. Jones major criteria – migratory polyarthritis, carditis, chorea, erythema marginatum, subcut nodules
e. Jones minor criteria – fever ,prolonged PR interval (sign of carditis), arthralgia, lab findings (↑ ESR/CRP, ↑ ASOT, ↑ anti-DNAse B) or positive throat swab
f. Dx requirements – evidence of strep inf AND at least 2 major or 1 major/2 minor criteria
4. What other ixs may be helpful?
a. ↑ ESR, Leucocytosis
b. ECG – prolonged PR interval, echo
c. Throat swab culture
5. What is your mgt plan?
a. Penicillin VK PO 10 days – to eradicate S.pyogenes
b. Bedrest
c. Aspirin/Anti-inflammatories – for fever, arthralgia, arthritis
d. LT prophylaxis – benzathine penicillin IM every 3-4 wks
i. 5 yrs since last episode or until age 18 (whichever is longer)
ii. If mild or healed carditis – 10 years duration or until 25 yrs age
iii. If severe carditis or valve surgery – lifelong prophylaxis
e. a
6. a
ESR = Erythrocyte sedimentation rate - ↑ settling when presence of inflam reaction (other proteins alter rbc electrostatic charge allowing them to stack)
Eg. Multiple myeloma – plasma b cell prolif produces v high ESR

• Strep throat
• Scarlet fever
• Impetigo, Cellulitis, Erysipelas
• Bacteraemia
• Focal infections
• Pneumonia
• Septic arthritis
• Osteomyelitis
• Toxic shock syndrome (TSS)
• Necrotising fasciitis


54 M
PC – 3/12 hx ↑ fatigue + intermittent R sided abdo pain
Meds – Naproxen for L hip OA – currently awaiting THR

Hb 115 (135-180) Anemia
MCV 69 (76-96) Mean corpuscular vol - ↓ = microcytic
MCH 23 (27-32) Mean corpuscular Hb conc
WCC 8.5
Platelets 495 (150-400) Thrombocytosis
ESR 42 mm/hr (1-20)
Red cells – hypochromic and microcytic w occasional pencil forms noted

1. Describe the main blood film abnormalities
a. Microcytic anemia
b. Mild thrombocysotis (may be 2ndry to iron deficiency +/- blood loss)
c. Raised ESR - ? hip OA, ulcer?
d. Pencil forms → feature of iron deficient anemia
2. What type of anemia is this?
a. Microcytic anemia
3. What are the possible causes of this anemia?
a. Iron deficiency
i. Low dietary iron
ii. NSAID related gastric ulcer – epigastric pain
iii. CRC – asc colon
b. Anemia of chr dis → iron block
i. Often assoc w ↑ ESR
ii. Tends to be normochromic or borderline microcytic/hypochromic
iii. Rare for Hb <90 g/L in chr dis alone
c. Thalassemia (globin chain defect) - unlikely in a pt of this age
4. How will you identify the cause of the anemia?
a. Iron studies – will distinguish iron deficiency from anemia of chr dis
b. In this pt → Iron deficiency
i. Serum Fe 4 (10-30)
ii. TIBC 84 (30-60)
iii. Saturation 0.05 (0.3-0.45)
iv. Ferritin 3 (20-250)
c. Difficulties interpreting iron studies – chr dis can mask the changes of iron deficiency – ie high iron binding capacity and low ferritin of iron deficiency can be normalised in the presence of chr dis
Iron saturation iron binding capacity ferritin
Chr dis ↓ - -/↑
Iron deficiency ↓ ↑ ↓
5. Management
a. Iron therapy (oral) + repeat blood tests
b. Fecal occult bloods
c. Gastroscopy + Colonscopy reqd for this pt

IRON deficiency is not a dx → its cause must be found!
Key points
• common causes of microcytic anemia – iron deficiency, thalassaemia, chr dis (usu normochromic and Hb >90 g/L)
• Fe studies – impt in differentiating chr dis

LAB MED TUTORIAL 3: Case 1 – Anemia

48M builder - PC - 3/12 ↑ fatigue, dyspnea on mild exertion
O/E – clinically anaemic, T 37.0, PR 100, BP 125/80

RCC 1.47 (4.5-6.5)
Hb 85 g/L (135-180)
PCV 0.25 (0.4-0.54)
MCV 126 (76-96)
MCH 42.2 (27-32)
RC morph abnormal
Plt 160 (150-400)
WCC 4.5 (4-11)
Seg N 1.23 (2-7.5)
Blood film – red cells (oval macrocytes noted), white cells (hypersegmented neutrophils present)

1. Major abnormalities present?
a. Anemia with macrocytosis and hypersegmented neutrophils (first sign of megaloblastic anemia)
2. What are the major causes of a macrocytic blood film?

a. B12 or folate deficiency
b. Liver disease
c. Alcohol
d. Hypothyroidism
e. Underlying bone marrow d/o eg myelodysplasia
f. Reticulocytes can also give a macrocytic blood film

3. What additional ixs would you require?
a. Vit B12 level
b. Serum and red cell folate
c. GGT
d. TFTs
e. Consider a bone marrow biopsy – if b12 results normal to excl myelodysplastic syndrome
f. Parietal cell and IF antibody testing
4. If vit b12 level found to be reduced, what is the likely dx? How might you confirm this? How would you manage the pt?
a. Causes of B12 deficiency
i. Diet – vegan
ii. Malabsorption
1. Pernicious anemia - >60yrs, F>M, assoc w autoimm diseases
2. Celiac dis
3. Crohns dis
4. Term ileum resection
5. Bacterial overgrowth
b. Pernicious anemia – most likely dx here, as he is young and changes are very marked
c. Confirmation
i. Parietal cell and IF antibody measurements
ii. Schilling test (no longer used clinically)
1. Part 1 – pt given b12 and urine b12 measured
2. Part 2 – pt given b12/urine and urine b12 remeasured
3. A abnormal part 1 and normal part 2 indicates abnormal IF (ie PA)
4. Both parts abnormal indicates B12/IF complex malabsorption (ie terminal ileum dis)
d. Tx - Vit b12 (neo-cytamen) 1000ug weekly x4 then 3/12
5. Can neutrophils and platelets ↓ in this d/o?
a. B12 and folate are involved in DNA synth – deficiencies effect all rapidly dividing cells
b. Incl other bone marrow cells, oral and GI mucosa – rbc’s however are most vuln
6. What non-hematological complications of vit b12 deficiency might you look for? → Neurological, Ø reversible with parenteral B12
i. Subacute combined degen of cord (distal paraesthesiae, ataxia, ↓ ankle jerks, extensor plantars) → screening
ii. Impaired mental function
iii. Visual impairment

1. Def - ↓ Hb (for age/sex) → ↓ O2 carriage → tis hypoxia → compensation (eg tachycardia to ↑ CO)
2. Sxs – SOB, weakness, lethargy, palpitations, angia-COPD exacerbation
3. Signs – pallor, tachycardia, worsening HF
4. Blood tests
a. PCV (pack cell vol) = 45% (haemotocrit)
b. MCV (mean cell vol) = rbc count x PCV = ~92 fl
5. Classifications – Pathogenetic vs Morphological
a. Pathogenetic
i. Impaired RBC formation
1. Substance deficiency – iron, b12, folate (inadequate intake or malabsorption)
2. Impaired bone marrow func – infiltration (eg leukaemia), irradiation, drug toxicity
a. AML → immature myeloid cells (3/52 – malaise, bruising, fever)
3. Genetic defect in production – eg thalassaemia
ii. Blood loss
iii. Excessive hemolysis - ↓ survival or intrinsic rbc problem
b. Morphological
i. Microcytic hypochromic anemia
1. Iron deficiency anemia - ↓ serum Fe, ↑ transferrin, ↓ iron sat, ↑ ferritin
a. Inadequate dietary intake
b. Malabsorption
c. ↑ demands (eg preg)
d. Blood loss
2. Anemia of chronic dis – iron block (↓ Fe, ↓ transferrin, saturation N, ferritin N)
3. Genetic – eg thalassaemia
ii. Macrocytic (megaloblastic) anemia (see above)

LAB MED TUTORIAL 3: Case 2 - Pneumonia

42 M
PC - R CP catches his breath every time he breathes, off food 1/7, feeling hot/cold, coughed up small amounts of sputum, 1x pack smoking /day
O/E – looks unwell, temp 39, PR 110, RR 20, dullness + ↓ breath sounds at R lung base
Microscopy – occasional epithelial cells, profuse G+ cocci w normal oral flora

1. What is your provisional dx
a. Puemococcal pneumonia – based on hx and G+ve cocci seen in microscopy
b. Other possible causes
i. Pneumonia caused by some other typical pathogen – eg h.influenzae, s.aureus
ii. Atypical pneumonia – mycoplasma, Chlamydia, legionella
iii. Viral pneumonia
iv. Aspiration pneumonia – mixture of G+ve/-ve bacteria (esp if alcoholic)
v. COPD acute exacerbation
vi. PE
vii. Bronchial carcinoma with a/w obstruction
viii. Other inf – eg TB
ix. Rib # causing CP (esp if alcoholic)
2. What is your mgt plan?
a. Confirm suspected dx of pneumonia + assess degree of severity which will guide tx decisions
b. CXR
i. Helps confirm dx
ii. Demonstrates other features eg pleural effusion, cavitation (suggesting abscess)
iii. Features of bronchial carcinoma
c. Assessing Severity
i. PORT severity index (more complicated)
ii. CURB criteria – 0 points 2-3% mortality, 1 = 8%, 2 = 23%, 3 = 33%, 4 = 83%
1. Confusion – 8 or less scored on a 10 point mini mental status questionnaire
2. Blood urea - >7 mmol/l
3. Respiratory rate >30 /min
4. BP – diastolic <60
iii. Further exmn and lab results reqd to assess severity – BP, confusion status, serum urea, haematological and biochem results, O2 sat, blood gas results
d. Medical mgt - Initial Tx empiric
i. Mild pneumonia Ø requiring hospi → amoxy 500mg tds OR erythromycin 500mg qid OR roxithromycin 300mg od
ii. Hospital but not severe → Amoxy 1g q6h IV PLUS erythromycin 500 mg q6H
iii. Hospital tx and severe → Cef 1.5g Q8H IV (or amoxy-clav 1.2g q6H) PLUS erythromycin 500 mg q6H
e. General Management
i. O2 therapy
ii. Smoking cessation
iii. Pneumococcal and influenza annual vaccinations
iv. F-up CXR at 6 weeks


58 F
PC – freq attacks of purulent sinusitis over 4y period; also suffered from 3x pn, non-smoker, Øallergies
Ixs - CT reveals pansinusitis and bronchiectatic changes in R middle lobe
Serum Igs
• IgG 3.6 g/L (7-16) ↓
• IgA <0.3 (0.4-2.5) ↓
• IgM <0.3 (0.8-4) ↓
• Serum protein electrophoresis – marked reduction in gamma region, no monoclonal bands

1. What are the abnormalities of significance?
a. Pan-hypogammaglobulinaemia (all immunoglobins reduced)
b. Low Igs → recurrent pn, pansinusitis, bronchiectasis (infections esp encapsulated organisms such as S.pneumoniae and H.influenzae) – due to IgG deficiency
c. Other likely infections – pharyngitis, otitis media
d. Monoclonal bands – suggestive of multiple myeloma (but 20% cases of MM only detected with paraprotein in urine)
i. Multiple myeloma – uncontrolled prolif of plasma cells → monoclonal antibody prodn
2. What other ixs are necessary?
a. Careful physical exmn – to excl lymphoma
b. FBC – to exclude CLL
c. Serum albumin – if low, consider protein losing conditions (eg nephrotic syndrome)
d. Urinanalysis – to exclude heavy proteinuria
e. Serumand urine protein electrophoresis (EPP) to excl multiple myeloma
f. CXR / CT – to exclude thymoma
g. Congenital cause – if pt younger, would have explored f.hx
h. Drugs
3. What is the likely dx?
a. CVID (common variable immune deficiency) – as all tests are normal
4. Mgt plan?
a. Refer to immunologist
b. Lifelong Ig replacement w IV pooled human serum Ig (IVIG) every 4 weeks – is 98% IgG, so lilttle change in other Ig levels
c. Prompt tx of infection


27 F
PC – 3/12 hx of joint pains, headache, intermittent CPs, fatigue
HxPC – 6 months prior to onset of these sxs, DVT after a flight; warfarin tx 3/12
O/E – faint rash on her checks, joints tender but Ø swollen
• Hb – 94 (115/165) ↓
• Red cell morphology – normal
• Platelets – 101 (150-400) ↓
• WCC – 3.8 (4-11) ↓
• ESR – 39 (0-20) ↑
Special tests
• ANA (anti-nuclear antibody) – Positive Titre 1:640 (antibodies still detectable at dilution factor of 640x)
• Anti-double stranded DNA - <7 (<7)
• Extractable nuclear antigens – Negative (don’t learn for this year)
• Anti-cardiolipin antibody (IgG) – 25 (<5); antibody against platelet phospholipid
• C3 – 0.67 (0.55-1.2)
• C4 – 0.21 (0.2-0.4)

1. Most likely dx?
a. SLE (systemic lupus erythematous)
b. ANA
i. Pts almost always ANA +ve
ii. ANA very sensitive but not specific
iii. Other conditions with ANA +ve result incl autoimmune conditions, some chr infections and can be normal
c. Anti-dsDNA antibodies
i. Far more specific for SLE but less sensitive (in only 60% of SLE subjects)
ii. Absence of anti-dsDNA does Ø exclude SLE
iii. Higher titres tend to correlate w more severe dis and renal dis
d. Complement levels
i. May be ↓ in active SLE due to accelerated complement activation
ii. However, reasonably insensitive indicator of activity bec accelerated b/down is often compensated by ↑ synth
2. What complication has developed?
a. 2ndry Antiphospholipid antibody syndrome
i. Hx of thrombosis
ii. Thrombocytopneia
iii. Positive anti-cardiolipin antibodies
b. Antiphospholipid syndrome
i. Features - thrombosis, recurrent miscarriages, thrombocytopenia)
ii. Anti-cardiolipin antibodies – found in APL antibody syndrome; may be primary or 2ndry to other automm conditions
iii. These antibodies can be found in some infections and some malignancies
iv. Lupus anticoagulant tests are often also positive in this condition
3. What other ixs would you perform?
a. Major concern
i. Pancytopenia
1. Due to SLE alone
2. Due to SLE plus anemia of chr dis (immune neutropenia/thrombocytopenia + anemia of chr dis)
3. SLE plus blood loss (pt is on warfarin)
4. Unrelated bone marrow pathology
b. Diet and menstrual hx – these contributing to the anemia
c. Iron studies – anemia of chr dis, blood loss
d. Fecal occult bloods – GI blood loss
e. Coagulation – expect ↑ PTT (paradoxical) in antiphospholipid syndr
f. LFTs/U+Es – lupus hepatitis
g. Urinanalysis – proteuria (nephritits)
h. Consider bone marrow exmn (debatable)
i. Best approach – tx the SLE, follow the blood count, if unclear – bone marrow biopsy may be indicated

SLE / Lupus
• Def - chr autoimm dis which can be fatal, course of the disease is unpredictable with flares alternating with remission
• Lupus is treatable symptomatically; mainly corticosteroids and immunosuppresants; currently no cure
Criteria for dx of SLE → 2x diagnostic lab tests AND 4 organ systems involved
Organ systems involved
1. Skin → butterfly rash, discoid rash, photosensitivity, oral ulcers, raynauds phenomenon
2. Cardiac → peri/myocarditis, endocarditis, conduction/valve anomalies, MI
3. Pulmonary → pleuritic pain, pleural effusion, acute/interstitial pneumonitis, alveolar hemorrhage, pulmonary HTN, idiopathic hypoxaemia
4. Hematology → haemolytic anemia, thrombocytopenia, leucopenia, antiphospholipid syndrome
5. Renal → proteinuria, cellular casts
6. MS → polyarthralgias, polyarthritis, myositis, myalgias
7. CNS → psychosis, seizures, transverse myelitis, stroke/TIAs
8. Others (not part of dx critieria) –
• Systemic – fever, fatigue, anorexia, weight loss, malaise
• GI – abdo pain, hepatomegaly

LAB MED TUTORIAL 4: Case 2 - Hyperlipidaemia

45 M – obese, hypertensive (BP160/95)
Lipid profile measured twice during CV risk assessment
Brother developed angina at 49, father had MI aged 54

Non fasting Fasting Ideal
Total cholesterol 9.4 8.1 mmol/L <4
Tg 12.7 7.4 mmol/L <2
HDL 1.1 0.9 mmol/L >1
Glucose 9.5 6.5 mmol/L 3.5-5.4

1. What are lipoproteins and what do they do? Of the major classes, which are likely to be ↑ in this pt?
a. Structure
i. Surface – composed of phospholipids, chol and apoproteins
ii. Core - TG, cholesterol-estere
iii. Apoproteins – target the lipoprotein particle to specific receptors for uptake into cells
b. In this pt – both cholesterol and TG are raised – so there must be ↑ in LDL and in one or both of the TG rich lipoproteins (VLDL or chylomicrons)
2. Draw a basic diagram showing the sources and fates of lipoproteins

3. Are this pts lipid results inconsistent?
a. Individual variability – typically 7% variability in an average individual
b. So – if true average chol is 6.0 mmol/L – readings will be betw 5.6 and 6.4 mmol/L on 65% of occasions (5.2-6.8 on 95%)
c. If in doubt of the first reading, repeat the test
d. TGs even more variable – marked variation due to recent food type and time taken → results are therefore not inconsistent
4. What 2ndry causes may be responsible for his lipid profile?
a. Diabetes, glucose intolerance or excessive alcohol intake
b. Poor diet, high fat intake – can cause marked further TG elev in people with poor lipid particle clearance
5. Can a dx of diabetes be made?
a. Not yet – dx requires fasting plasma glucose of >7 mmol/L or random BG of >11.1
b. Clear sxs – only 1 test reqd (if asx – 2x tests reqd)
c. Fasting glucose is abnormal → impaired fasting glucose
d. If doubt – oral GTT performed
6. What factors are most impt with regard to CVD risk?
a. Male
b. Age
c. Cholesterol
d. DM
e. Smoking
f. HTN
g. But Framingham – does not a/c for f.hx (this pt at higher risk)
h. Previous CVD event – eg MI, stroke, PVD, angina → high risk
7. What physical signs are assoc w lipid disorders?
a. Tendon xanthomata – almost diagnostic of familial hypercholesterolemia
b. Xanthelasma and arcus cornealis – soft signs (can occur in N people)
8. Briefly discuss possible txs for this pt?
a. Diet - ↓ fat, ↓ alcohol
b. Exercise
c. Drugs – statins or fibrate
d. Improvement in glycaemic control
9. Key points
a. Chol and TG measurements vary in an individual
b. Causes of combined hypercholesterolaemia dn triglyceridaemia incl –
i. DM/Glucose intol
ii. Excess alcohol
iii. Poor diet with high fat intake
iv. Genetic predisposition
v. Drugs – eg steroids
c. Dx of DM requires at least 1x fasting BG of >7 mmol/L (or if random >11.1) – 1 if sxs, 2 if asx


76 F
Develops diarrhea 9 days post hosp adm for a RTI complicated by falls
Microscopy of faces –
1. Wet film – white cells (large amount), red cells (large amount), mucus (large amount)
2. Culture – to follow

What is the likely pathogenesis of her diarrhea?
1. Antibiotic assoc diarrhea – common, 25% w augmentin, usu less severe than Cdifficile diarrhea (may be florid + serious consequences)
2. C.difficile diarrhea (pseudomembranous colitis)
a. Result of A/B tx in a person colonised with C.difficile (rare in community <5%, common after hosp admission ~10%)
b. C.difficile carriage usu asx, organism readily isolated from hands of health care workers and hosp evt
c. C.difficle colitis – occurs after A/B tx where normal commensual gut flora normally act to inhibit C.difficile
d. C.difficle then proliferates and causes colitis by releasing a number of toxins
i. Toxin A → diarrhea (mucosal secretion + permeability)
ii. Toxin B → cytotoxic (cell death)
e. Disease characterised by severe diarrhea, abdo cramping and fever (<1 month of starting A/B tx)
f. Antibiotics – greatest risk with 3rd gen cephalosporins and augmentin
g. Colonoscopy → red inflamed mucosa and areas of white exudates (called pseudomembranes) on the surf of the LB
i. Necrosis of mucosal surface occurs underneath the pseudomembranes
h. Disruption + shedding of mucosal lining

How should the diarrhea be investigated and how reliable are the results of the ixs?
1. Differentials
a. IBD – bloody diarrhea, abdo pain, negative culture
b. Gastroenteritis – salmonella, campylocbacter – blood may be pres in stools, but usu not vis
c. White cells in stool – likely bact inf of LB
2. Ixs
a. Stool samples – C.difficile toxin testing (confirmation of dx) – reqs 3x neg tests to excl (only 80% sens)

How should she be treated?
1. Discontinue initial A/B
2. Metronidazole (flagyl) 400 mg tds PO 10 days
a. Vancomycin – 2nd line – equally effective but concerns over resistance and cost
b. Neither metro or vancomycin oral absorbed into bldstrem
3. Meticulous hygiene practices – transmission by fomites can occur


65 F
PC – presents w 2/7 hx fever, vomiting and backache
MSU Initial results –
• white cells 50 x 10(6)/L
• red cells 6 x 10(6)/L
• epithelial cells 2 x 10(6)/L
• bacteria small numbers
Culture – heavy growth Proteus mirabilis, sensitivities to follow

1. How do you interpret these results?
a. >10 x 10(6)/L suggests infection
i. <10(5) is unlikely to be inf, >10(8) in presence of single organism pathognomonic, betw these two, interpret according to clinical picture
b. Small numbers of epithelial cells suggest not contaminated urine
c. >10(8) bacteria/L suggest infection
d. Proteus is a common cause of UTI (a mixed growth is usu due to contamination)
2. What is your mgt plan?
a. Backache suggests pyelonephritis rather than cystitis / uncomplicated UTI
b. Adm to hosp if unwell/severe infection and given A/Bs
i. At home
1. Trimethoprim 7-10 days
2. Augmentin 7-10 days
3. Norfloxacin
ii. If admitted
1. Gent single dose followed by trimethoprim
2. IV augmentin (if vomiting)
c. Repeat MSU and urine culture 2-4 wks after completion of tx is impt
3. She has a enterococcus faecalis UTI in 6 months time? What should be done?
a. If recurrent infection or failure to respond to tx – you must find out why
b. Plan axr – look for obstruction, stones or morphological abnormalities
c. US
d. +/- IVU
e. Education (effectiveness uncertain) – urinating after sing, good fluid intake, wipe front to back

LAB MED TUTORIAL 5: Case 2 – Hepatitis A

35 M homosexual in food industry
PC - mild fever, malaise, jaundice
Initial lab results –
Albumin 32 (35-47)
Total protein 56 (62-80)
Globulin 24 (25-35)
Total bilirubin 85 (2-20)
GGT 423 (0-60)
ALP 265 (25-110)
AST >800 (5-45)
ALT >800 (0-45)

1. Interpretation of results
a. Albumin/Globulin – generally slow to reflect liver damage
b. AST/ALT – most sensitive test for acute hepatocellular injury
c. ALP – best indicator of biliary obstruction
d. Patterns
i. Inflammation of liver cells (hepatic pattern) → AST and ALT sky high, moderate ↑ in bilirubin, GGT and ALP
ii. Obstructive (biliary tract) → bilirubin and ALP high, mild incr in AST/ALT (eg cholecystitis, stones, pancreatitis)
2. What are the likely causes of infection?
a. Hepatitis A, B or C
b. EBV (GF) or CMV infection
c. Drug reaction
3. What further ixs would be helpful?
a. Hepatitis A IgM (HAV IgM) – acute phase (<6 months), HAV IgG for immune status
b. Hep B sAg – indicates infection
c. Hep B sAb
d. Hep B cIgM – indicates recent HBV infection
e. Hep C antibody (HCV Ab)
g. Paul Bunnell / Monospot – pt has sore throat, you suspect GF but monospot negative
i. EBV IgG pos and EBV IgM negative – had GF in the past, no infection now (and vice versa)
h. CMV serology
4. How should his illness be managed? When should he be allowed to return to work?
a. Assess severity – check INR, look for encephalopathy, bleeding, infection → admit if unwell
b. Supportive therapy – fluids, vit k, coagulation factors
c. Tx – no specific tx available → Tx coagulopathy, encephalopathy, hypoglycaemia etc as needed
d. Public health – Hep A,B and C are notifiable diseases
e. This man can go back to work when feeling well – Hep B and C not spread by faecal oral route
i. Levels of Hep A are highest before the pt feels unwell – people living in same house for the two weeks before the onset of sxs should be immunised for Hep A or B depending on the dx
f. He should expect to feel well again in a few weeks - month

LAB MED TUTORIAL 5: Case 3 – Hepatitis B and Treponema

23 F
Asx women in first pregnancy found w following serological results

HBsAg – pos
Anti-HB core IgM (anti-HB core) – neg
Anti-HB core – pos
HBeAg – pos
Anti-delta – neg

Treponemal screen – reactive
RPR – positive
TPHA – reactive

1. What do the hepatitis B serology results indicate?
a. HB sAG → Chr Hep B infection
b. Negative IgM anti-core makes it very unlikely that her hepatitis B infection is acute (<6 months)
c. Anti-HB core → indicates chr inf
d. She is highly infectious to others as indicated by her HBeAg result (HBV DNA more accurate indicator if infectiousness)
e. Anti-delta – no co-infection with HDV (can only infect people w HBV)
2. What is your mgt plan in light of the hepatitis B results?
a. Risk of infant being infection with Hep B at birth is high (~90% in absence of any intervention)
b. If infected, the chance the infant will become a lifelong chr carrier of Hep B is also high (~90%)
c. Infection of the neonate can be prevented by administering Hep B immune globulin (IgG) to the infant at birth followed by Hep B vaccination started in the first week of life
d. The women’s family and other contacts should be tested and those found to be susceptible should be vaccinated against Hep B
3. What advice can you give her for the future?
a. The late consequences of chr Hep B infection are cirrhosis and HCC
b. Avoid other causes of harm to the liver – eg minimise alcohol consumption
c. There is uncertainty about whether it is cost-effective to screen all pts w chr HBV inf for the devt of cirrhosis +/- HCC with 6/12 LFTs and alpha feto-protein (AFP) +/- liver US
d. ?Tx w interferon-a or lamivudine
4. What do the treponemal serology results indicate?
a. The treponemal screen test and the TPHA (treponema pallidum haemagllutin assay) are specific tests for tremponemal inf
i. Treponemal screen positive – indicates further testing
ii. THPA – specific tremponemal antibody test (usu positive for life)
iii. Both are positive which indicates she has been infected (at some time) with a treonema
iv. Most likely treponema pallidum (syphilis) or the treponema pallidum subspecies pertenue (cause of yaws)
b. RPR (rapid plasmin regain) test is non-specific test (sim to VDRL)
i. Positive test result suggests active dis – but they are slow to fall (may take some years after successful tx)
c. The results here are consistent w untreated syphilis and should not be dismissed as either biological false positive or as indicators of past yaws
5. What is your mgt plan in light of these results?
a. Examine for signs of syphilis – eg chancre, regional L/A, skin rash
b. Lumbar puncture – CSF examined for incr cell count or protein and for serology
c. If any of these tests are positive – tx for neurosyphilis w 10 days IV benzyl penicillin
d. If CSF parameters are normal – tx w 3x IM injections of benzathine penicillin at weekly intervals
e. Her baby should be carefully followed for any evidence of congenital syphilis (unlikely if mother has received tx)

Key Points
1. Hep B IgM anti-core antibodies are positive in acute Hep B infection
2. Positive HBeAg indicates high infectivity
3. Neonatal infection highly likely if mother infectious and highly likely to result in chr carrier state
4. Prevent neonatal inf w Hep B immune globulin at birth and Hep B vaccination started in the 1st week of life
5. Chr Hep B inf can lead to cirrhosis and HCC
6. Treponemal screen test and THPA are specific for treponemal infection - specific tests indicate infection at some time
7. RPR is non-specific – indicates dis activity and becomes negative after tx

LAB MED TUT 5: Case 4 – Strep Throat

3 Boy
PC – recurrent sore throat
O/E – febrile, Temp 37.8, red enlarged tonsils, some tender cervical nodes, no purulent exudates in throat
Throat swab
Culture – normal oral flora – light growth of S.pyogenes
Sensitive to Penicillin and Erythromycin

1. Value of taking throat swabs in children
a. Identification of children who require A/B tx due to risk of RF (S.pyogenes infections) and those children who do not require antibiotics (usu viral)
b. Some children have S.pyogenes in their throats as a commensals which means they receive unnecessary A/Bs with this approach but this is unavoidable
c. A/Bs do not relieve the sxs but they do prevent RF
2. Test all children or be selective in who you test with throat swabs?
a. Not practical to swab all sore throats
b. Children w bacterial sore throats tend to have purulent exudates and tender cervical L/A
c. Cough and hoarse voice are more common w viral sore throats
3. Would you prescribe this boy antibiotics?
a. Yes (in this case) – even though bacterial growth is light
b. Penicillin VK, Amoxycillin, Erythromycin (or Cefaclor) – 10 days
c. Ideally wait until lab result return before starting tx
4. Role of tonsillectomy in children w recurrent sore throats?
a. Major acute complication of surgery → bleeding, no known LT consequences
b. Current view (not evidence based) → surgery is effective at ↓ symptomatic infections in children who need repeated courses of A/Bs and are missing a lot of school
5. Management of sore throats in adults?
a. 20+ yrs age → extremely unlikely to get RF
b. Unnecessary to take a swab or give A/Bs

Key Points
1. Throat swabs allow one to appropriately tx sore throats
2. Tx of S.pyogenes does not alter sxs but is impt in preventing RF
3. Bacterial sore throats tend to have purulent exudates and tender cervical nodes
4. Throat swabs in adults are not useful

LAB MED TUT 6: Case 1 - AIDS

25 M
PC – lethargy, weight loss (5kg last 3/12), pain on swallowing 1/52)
O/E – obvious weight loss, looks anemic, moderately severe oral thrush + collection of 3-4 rubbery lymph nodes (each 2cm in diameter) in left post cervical triangle

1. Differential Dx
a. HIV Infection with progression to AIDS
i. Oral thrush assoc w esophageal candidiasis → dysphagia
ii. Weight loss
1. May be explained by esophageal candidiasis
2. Other causes should be considered -
a. Opportunistic infections eg penumocystic pn
b. TB – pulmonary or extrapulmonary
c. AIDS related malignancy – eg Non-hodgekins lymphoma
iii. Most common causes of L/A in HIV are -
1. Immune responses to HIV itself → generalised L/A at time of seroconversion (4 wks post infection) and which may persist for several months in some pts (fever, L/A, rash) – unlikely here as esophageal candiasis assoc w later stages of AIDS and focal L/A
2. Inf of lymph nodes – usu M.tuberculosis
3. Non-Hodgekins lymphoma (AIDS related malignancy)
iv. L/A occurrence late in HIV course (indicated by thrush) suggest TB or NH lymphoma
b. Lymphoma with assoc weight loss but HIV neg (possible but definitely still requires HIV test as strong assoc betw HIV infection and lymphoma)
2. Ixs
a. HIV Test antibody test
i. Pre test Considerations
1. Consent
2. HIV test not AIDS test
3. Window period ~4 wks
4. Significance of pos test → medical, psych, social, discrimination issues (HIV not notifiable)
5. Encryption of test form for anonymity
6. Safe sexual beh
7. Safe injecting
8. How results of test are obtained
ii. Post-test counselling
1. In person
2. Explain test result → need for confirmatory test, viral load, CD4 count
3. If neg → window period, high beh, repeat test, prevention
4. If HIV antibody positive, evaluate progression of HIV inf → viral load, CD4 count
b. FNA (L/A)
i. Microscopy and culture for acid fast bacilli
ii. Histopathology for cytology to detect malignant cells
c. Biopsy
i. Reqd if cytology suggests lymphoma → lymph node architecture + cell morphology – to classify lymphoma type
ii. Either core biopsy or surgical biopsy
d. If lymphoma confirmed → staging
i. CT scan chest, abdo, pelvis
ii. Bone marrow examination
e. Routine Ixs
i. FBC, biochem
ii. Clinical dx for oral candiasis usu sufficient – oral swab may be helpful for microbiological proof
3. Tx while awaiting lab results
a. Oral ketaconazole 200 mg bd 7 days usu effective to cure esophageal candiadiasis (oral mycostatin not adequate)
b. Fluconazole 100 mg bd 7 days – occasionally in pts if ketaconazole ineffective (more expensive)

Key Points
1. Consider HIV inf in anyone w L/A
2. HIV testing must be accompanied by effective pre-test and post-test counselling
3. Initial ix of L/A involves FNA followed by biopsy if reqd
4. Impt to co-ordinate processing etc with the lab
5. Microbiology is impt as TB may otherwise be missed

LAB MED TUTORIAL 6: Case 2 – Multiple Myeloma

55 F
PC – severe midline thoracic back pain, smoker 10 pack years, recently developed nocturia x2
O/E – pale, tenderness over mid-thoracic sp, no finger clubbing, lat CXR shows crush # of T4
Lab – normocytic, normochromic anemia

Calcium 3.91 ++
Phosphate 1.45 +
Total protein 93 +
Albumin 28 –
Urea 14.7 +
Creatinine 170 + (60-120)

Intepretation of Results
1. Hypercalcemia
a. Etiology
i. Common
1. Malignancy
2. Primary hyper-parathyroidism
ii. Less common
1. Granulomatous diseases
2. Hyperthyroidism
3. Vitamin D intoxication
2. Albumin Levels
a. Impt in establishing whether there has been a change in inactive, protein bound calcium or in active, free calcium
b. Calculate the corrected calcium
i. Corrected calcium = total calcium + 0.02 x (40 – albumin)
c. In this pt
i. Corrected calcium = 3.91 + 0.02 x 12 = 4.51
ii. Low albumin means that the protein bound fraction is reduced and the ionised calcium is proportionally ↑
3. Phosphate (poor man’s PTH)
a. PTH stimulates phosphate loss in urine
b. Hyperparathyroidism typically shows high calcium and low serum phosphate
c. Hyperparathyroidism of malignancy can be due to PTHrP (PTH related peptide) or due to bone destr
d. Tumors making PTHrP have typical high Ca / low PO4
e. In direct tumor bone lysis, PO4 is usu normal-high
f. Vitamin D excess – both calcium and PO4 are high
g. Phosphate levels are difficult to interpret in pts w RF as PO4 levels ↑ as GFR ↓

1. Malignancy on hx and exmn
a. Low albumin more common in those w malignancy than those with hyperparathyroidism
b. Raised phosphate not typical of hyperparathyroidism
c. Raised total protein (albumin + globulin) suggests myeloma
d. Lung ca would not explain the elev total protein
2. Ixs
a. PTH test –↑ in hyperparathyroidism, ↓ in malignancy
b. Serum and urine protein electrophoresis → monoclonal peak
c. Skeletal survey → lytic lesions
d. ?Bone marrow biopsy

Renal Impairment - ↑ Urea and Creatinine
1. Renal impairment in myeloma can be caused by hypercalcemia
a. Damaged caused by myeloma paraprotein
2. Very high serum calcium can ↑ U/O → diabetes insipidis like state
a. High calcium → polyuria → even high calcium …… (vicious cycle) → severe dehydration possible
3. Dehydration → ↑ pre-renal component of renal impairment

1. Rehydration N saline → allows for ↑ renal excretion of calcium
2. Bisphosphonates (pamidronate) → tx of hypercalcemia and reduce bone destr in myeloma

Key Points
1. Most common causes of hypercalcemia – malignancy and primary hyperparathyroidism
2. Impt to calculate the correct calcium to adjust for changes in the protein bound form
3. Hyperparathyroidism → high PTH, high calcium, low phosphate
4. Hypercalcemia of malignancy → low PTH, high calcium, phosphate normal-high
a. Exception – PTHrP production – eg breast, lung, urogenital ca where phosphate low
5. Phosphate levels ↑ as GFR falls
6. Raised globulins – consider multiple myeloma
7. First line tx for hypercalcemia is rehydration followed by bisphosphonates (rapid acute correction)

Multiple Myeloma

1. Defintion
a. Malignant dis of plasma cells of bone marrow
b. Clonal proliferation of bone marrow plasma cells that produce monoclonal immunoglobulins (M proteins or paraproteins) → most cases IgG or IgA
c. The paraprotein may be assoc w light chains in the urine (either κ or λ)
d. 1% of all malignant dis
2. Clinical features
a. Peak age 60y
b. Neoplastic cells induce excess osteoclastic activity
i. Osteoporosis
ii. Osteolytic lesions
iii. Pathological fractures
iv. Hypercalcemia
c. Presenting complaints
i. Bone pain (most common)
ii. Progressive marrow infiltration
1. anemia
2. infections
3. bleeding
iii. Renal failure due to -
1. light chain deposition in tubules
2. hypercalcemia
3. hyperuricaemia
4. amyloid deposition in kidneys
iv. Paraproteins may form aggregates in the blood leading to incr viscosity
3. Investigations
a. Plasma cell infiltration on bone marrow aspirate or trephine biopsy
b. Osteolytic bone lesions on skeletal survey
c. Monoclonal (M) bands on serum protein electrophoresis
d. Urine electrophoresis
i. 24 hr urine immunofixation to assess light chain excretion
e. Blood count
i. Anemia
ii. Thrombocytopenia
iii. Leucopenia
iv. ESR elev
v. Total protein = albumin + globulins (expect incr total protein, incr globulins, albumin down)
f. Biochemistry
i. Urea/Creatinine elev
ii. Hypercalcemia
4. Management
a. Supportive therapy
i. Blood transfusion or EPO
ii. Prompt tx of infections
iii. Tx of bone pain w radiotherapy or NSAIDs (beware renal impairment)
iv. Rehydration therapy for renal failure, hypercalcemia
v. Bisphosphonates – reduction in bone pain w LT administration
b. Chemo
i. Alkylating agents + Prednisone
c. Median survival 5 yrs


64 M
PC – hx of headaches, past med hx includes a previous PU and intermittent attacks of gout, non-smoker
O/E – no abnormal findings

FBC rcc 7.5 + 4.5-6.5)
Hb 182 + (135-180)
PCV 0.68 +++ (0.4-0.54)
MCV 81
MCH 24.3 (27-32) → hypochromic
RC morphology abnormal
Platelets 620 ++
Wcc 13.2 +
Metamyelocyte 0.13 (immature white cell that should never be present in blood)
Band neutrophils 0.13 (0-0.6) – metamyelocyte → band neutrophil → segmented neutrophil
Segmented Neutrophils 10.2 ++
Blood film – red cells incre number of microcytes and hypochromic cells

1. Abnormalities
a. ↑ Hb
b. ↑ wcc
c. ↑ platelets
d. Hypochromic microcytic red cells
e. Hb and PCV highly suggestive of polycythemia
i. Primary polycythemia (PRV)
ii. 2ndry polycythemia eg CORD
iii. Spurious
f. Presence of basophils and release of immature white cells (metamyelocytes) into circ (left shift) suggest a marrow d/o like polycythemia rubra vera (PRV) rather than a 2ndry cause
2. Possible causes of ↑ Hb
a. Relative Polycythemia
i. Spurious (haemoconcentration) – eg diuretics causing dehydration
b. True Polycythemia
i. Primary
1. PRV - PU and gout are ↑ in people w myeloproliferative d/os
ii. 2ndry
1. Appropriate EPO response
a. High altitude
b. Chr lung dis
c. OSA
d. Congential HD
2. Inappropriate EPO response
a. Renal dis eg RCC, hydronephrosis, polycystic kidney
3. Additional Ixs
a. Red cell and plasma vol – determine whether true polycythemia
b. CXR – assess cardiorespiratory dis
c. O2 sat – chr hypoxia
d. U/S abdo – renal cell carcinoma, splenomegaly
e. Urate – incr consistent w myeloproliferative d/o like PRV
4. Initial management
a. Venesection – PCV to 0.45
b. Myelosuppression reqd if poor response to venesection or rebound incr in platelet count – Hydroxyurea
c. Prognosis good – median survival 10-12 yrs
d. Up to 30% of PRV may evolve to myelofibrosis
e. In 2ndry polycythemia, raised Hb is compensatory – venesection may be reqd if pt is getting sxs of hyperviscosity
f. Red cells are microcytic in this pt bec of the expansion of the red cell mass and devt of latent iron deficiency
i. Iron replacement would not be given as it may incr Hb further

Key Points
1. Causes of raised Hb
a. Spurious/Stress
b. True
i. Primary – PRV
ii. 2ndry – High altitude, chr lung dis, haemoglobinopthy, congenital HD, OSA, renal dis
2. Ixs
a. Red cell and plasma vol
b. CXR
c. O2 sat
d. U/S abdo
e. Urate
f. EPO
3. Primary mgt venesection

Polycythema vera

• Myelodysplastic syndromes – characterised by ineffective erythropoiesis and peripheral blood cytopenias
• Myeloproliferative d/os – characterised by overproduction of one or more cell lines (myeloid, erythroid, or megakaryocyte); comprises DML, PRV, essential thrombocythaemia and myelofibrosis
• Acute leukaemias – also clonal proliferation of a single cell line, but here the cells do not differentiate normally and there is progressive accumulation of immature cells
• Polycythemia = ↑ Hb, ↑ PCV, ↑ RCC
• Polycythemia vera is a myeloproliferative d/o characterised by excessive proliferation of erythroid, myeloid and megakaryocytic progenitor cells (escape of marrow stem cells from EPO control)
• S/S – due to hypervolaemia and hyperviscosity

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