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2001 FRACP paper one

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Question 1 top Download the PDF

A 47yo woman with overt thyrotoxicosis is found to have aortic stenosis. Which one of the following features, if present in this woman is most likely to indicate the need for aortic valve replacement?

A. A peak systolic left ventricular aortic pressure gradient of 60mmHg
B. The presence of NYHA class III angina
C. A resting heart rate > 120/min
D. An aortic valve orifice area of 0.9cm2
E. The presence of concomitant moderate aortic regurgitation

Answer: D

Issues in the question:
1. That the indications for aortic valve replacement are symptoms
2. The patient has overt thyrotoxicosis which could contribute to the symptoms

Definition of each option:

A. Peak systolic left ventricular aortic pressure gradient

  • This is the gradient between the ventricle and aorta during systole
  • In aortic stenosis the left ventricular pressures increase due to contraction against a smaller opening and can be up to 400mmHg
  • A gradient of >75mmHg is indicator of severe disease
    ***so answer is NOT A

B. NYHA class III angina

NYHA functional classification

I cardiac disease causing no limitations to physical activity
ordinary activity does NOT cause undue fatigue, palpitation, SOB, angina

II cardiac disease resulting in slight limitation of physical activity
comfortable at rest ordinary activity results in fatigue, palpitation, SOB, angina

III Cardiac disease causing marked limitation of physical activity
Comfortable at rest Less than ordinary physical activity causes fatigue, palpitation, SOB, angina

IV Cardiac disease with inability to carry out any physical activity w/o discomfort Symptoms of cardiac insufficiency or angina at rest
Discomfort increased with physical activity

Effects of thyrotoxicosis on the heart:

Parameter and Finding

  • Heart Rate Increased
  • Systemic vascular resistance Decreased
  • Cardiac output Increased
  • Ejection fraction Increased
  • Diastolic relaxation Increased
  • Diastolic blood pressure Decreased
  • Myocardial oxygen consumption Increased
  • Anginal syndrome Can induce or worsen

***given that answer B is likely a result of the thyrotoxicosis it would not be an independent indicator for need of valve replacement unless she was treated and still had angina

C. Heart rate >120

• Heart rate is not an indicator for surgery
***so the answer is NOT C

D. Aortic valve orifice

Normal Values:

  • Normal valve area: 3.0 to 4.0cm squared
  • Valve gradient: minimal until valve area is less than half

Symptoms occur when:

  • Valve area less than 1.0cm2
  • Aortic jet velocity 4.0m/sec
  • Mean transvalvular gradient greater than 40 mmHg

***severe disease is the only indicator for replacement answer IS D

E. Presence of concomitant Aortic Regurgitation

  • From what I’ve read there is mild AR in all AS and commonly more severe
  • AR does not appear to be an independent indication for surgery but its presence usually means that symptoms develop earlier and so patient has replacement earlier.
    ***therefore the answer is NOT E

Topic

Cardiology - Valve Disease - Aortic Stenosis




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Question 7 top Download PDF

Graft-versus-host disease is a major complication of allogeneic stem cell transplantation for haematological malignancy in adults.
Which one of the following has the least influence on the risk of developing graft-versus-host disease?
A. Age of recipient.
B. Donor-recipient ABO blood group incompatibility.
C. In vitro T cell depletion of the graft.
D. Type of HLA-matched donor (sibling versus unrelated).
E. Donor-recipient HLA mismatch.

Answer: B

Graft versus host disease (GVHD)

  • most frequent complication after allogeneic hematopoietic cell transplantation
  • is due to an intricate immune response following allogeneic stimuli
  • can be acute and/or chronic
  • is caused when T-cells of the donor recognize the presence of histocompatibility antigens in the host which differ from those of the donor cells
  • initial antigen recognition is followed by amplification of the T-cell recognition process.
  • proliferation of activated T-cells leads to the production and secretion of a variety of cytokines which are responsible for the inflammatory effects and tissue damage associated with GVHD
  • Much of the damage is caused by inflammatory cytokines (IL-1, IL-2, TNF, and gamma-interferon)
  • Divided into acute and chronic disease based upon onset

Acute GVHD      =­ disease presenting <100 days post stem cell transplantation
Chronic GVHD = onset of disease after the first 100 days.

  • Risk factors of acute v chronic GVHD differ somewhat
  • Major risk factors for the development of GVHD are:
  1. Histoincompatibility between donor and patient
  2. Older patient (and possibly donor) age
  3. Greater intensity of the transplant conditioning regimen
  4. Use of peripheral blood progenitor cells rather than marrow as a source of stem cells (certainly for chronic GVHD)
  5. Donor/recipient sex mismatch, especially with allosensitized female donors

Risk factors for Acute GVHD:

  1. HLA disparity
  2. Increasing age
  3. Donor and recipient gender disparity
  4. Type and status of underlying disease
  5. Amount of radiation delivered
  6. Doses of methotrexate and cyclosporine or tacrolimus

Risk Factors for Chronic GVHD:

  1. Higher degree of HLA mismatching
  2. Older age
  3. Subacute GVHD detected by skin biopsy or buccal mucosal biopsy
  4. History of high-grade acute GVHD
  5. Administration of unirradiated donor buffy coat transfusions
  6. Previous splenectomy
  7. Cytomegalovirus seropositivity (donor and recipient)

In terms of the question:

  1. Age of recipient
  • Older age is associated with increased likelihood of acute and chronic GVHD
  • This is also true of older age of donor
  • . Donor-recipient ABO blood group incompatibility.
  • In vitro T cell depletion of the graft
  • Incidence of acute GVHD in pts who receive donor cells from which T lymphocytes are not depleted in vitro is 10 – 80%
    • Type of HLA-matched donor (sibling versus unrelated) and Donor-recipient HLA mismatch
    • These both refer to matching of HLA antigens
    • The more matched the donor is the more likely they are to not cause GVHD

    Topic

    Haematology:Transplantation

    Question 8 top

    Question 9 top Download PDF

    The most useful investigation for the diagnosis of multiple sclerosis is:
    A. cerebrospinal fluid protein concentration.
    B. visual evoked responses.
    C. magnetic resonance imaging (MRI) scan of the brain.
    D. serum oligoclonal bands.
    E. cerebrospinal fluid microscopy.

    Answer: C

    • Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system (CNS).
    • Primarily affects women of Northern European descent who are of child-bearing age
    • Is characterized pathologically by multifocal areas of demyelination with loss of oligodendrocytes and astroglial scarring
    • Axonal injury is increasingly recognized as a prominent pathologic feature of MS.

     

    • The diagnosis of MS is a clinical one
    • Ancillary tests are used to support the clinical diagnosis BUT without clinical features no diagnosis can be made
    • The fundamental part of the diagnosis is:
    • Dissemination in place
    • Dissemination in time
    • These can be defined clinically or radiologically

     

    MRI is the test of choice to confirm the clinical diagnosis of Multiple Sclerosis

    • MRI detects many more MS lesions than CT
    • is able to detect plaques in regions that are rarely abnormal on CT such as the brain stem, cerebellum, and spinal cord
    • Most lesions seen on MRI correlate with pathologic lesions

     

    • Patients with clinically definite MS have typical white-matter lesions on MRI in >90% of cases.
    • MRI is more sensitive and specific for predicting evolution to clinically definite MS than other studies such as CT scans, CSF parameters, or evoked potentials

     

    MACDONALD CRITERIA


    Clinical features

    Additional data needed for diagnosis

    Two or more attacks; objective clinical evidence of two or more lesions

    None

    Two or more attacks; objective clinical evidence of one lesion

    Dissemination in space, demonstrated by:
    - MRI or
    - Two or more MRI-detected lesions plus positive CSF or
    - Await further clinical attack implicating a different site

    One attack; objective clinical evidence of two or more lesions

    Dissemination in time, demonstrated by:
    - MRI or  Second clinical attack

    One attack; objective clinical evidence of one lesion (monosymptomatic presentation; clinically isolated syndrome)

    Dissemination in space, demonstrated by:
    - MRI or 
    - two or more MRI-detected lesions consistent with MS plus positive CSF
    AND
    Dissemination in time, demonstrated by:
    - MRI or Second clinical attack*

    Insidious neurological progression suggestive of MS

    One year of disease progression (retrospectively or prospectively determined) AND  
    Two of the following:
    - Positive brain MRI (nine T2 lesions or four or more T2 lesions with positive VEP)
    - Positive spinal cord MRI (two focal T2 lesions)
    - Positive CSF

     

    OTHER INVESTIGATIONS:
    1. CSF analysis:

    • Qualitative assessment of CSF for oligoclonal bands using isoelectric focusing is the most important diagnostic CSF study when determining a diagnosis
    • LP should routinely include the measurement of opening pressure
    • CSF analysis should routinely include WCC and differential, protein and glucose

    Appearance

    Grossly normal

    Pressure

    Normal

    Leucocyte count

    Normal 2/3
    Lymphocytes are predominant
    If raised should raise suspicion of ddx

    Protein

    Normal
    Albumin is not synthesized in CNS  + gives a better indication of BBB disruption

    Glucose

    Normal

    Immunoglobulin

    ↑ of immunoglobulin level relative to other protein components
    Mainly IgG  -  with an XS IgG lambda and kappa light chains
    Abnormality is found in 90% of clinically definite MS pts

    CSF protein concentrations:

    • CSF protein (or albumin) level is usually normal
    •  Albumin is not synthesized in the CNS and therefore gives a better indication of BBB disruption than does total protein some of which may be synthesized within the CNS (eg, immunoglobulin).
    • Abnormality in IgG is found in 90% of MS patients
    • BUT is not a diagnostic feature

     
    2. Evoked potentials —

    • Measure CNS electrical events generated by peripheral stimulation of a sensory organ
    • used to detect abnormal CNS function that may be clinically undetectable
    • allow detection of a subclinical lesion in a site remote from the region of clinical dysfunction supports a diagnosis of multifocal MS
    • EPs also may help define the anatomical site of the lesion in tracts not easily visualized by imaging (eg, optic nerves, dorsal columns).

    The three most frequently used EPs are

    • somatosensory (SSEP)
    • visual (VER)
    • brainstem auditory evoked potentials (BAEP)
    • 85% of pts w clinically definite MS have abnormal VERs
    • 77%  have abnormal SSEPs, inc 50% of those who do not have sensory signs or symptoms
    • BAEP abnormalities are less frequent in MS than VER or SSEP abnormalities (67%)

     

    Guidelines from the American Academy of Neurology (AAN) state:

    • VERs are probably useful for identifying patients with clinically definite MS
    • SSEPs are possibly useful
    • insufficient evidence at this time to recommend BAEP as a useful test for diagnostic purposes

    3. Serum oligoclonal bands.

    • Oligoclonal bands are present in the CSF of approximately 90% of MS patients
    • A patient is considered positive for CSF oligoclonal bands if there are two or more bands in the CSF immunoglobulin region that are not present in the serum
    • In order to confirm local production of oligoclonal IgG in CSF you need a matched serum sample
    • Oligoclonal bands present in CSF, but not in serum, indicate CNS production.
      • Up to 8% of CSF samples from non-MS patients also contain OCBs; most are the result of chronic CNS infections, viral syndromes, and neuropathies.
      • presence of OCBs in monosymptomatic patients predicts a significantly higher rate of progression to MS than the absence of bands
      • quantification of OCBs is an insensitive prognostic indicator
      • the presence of OCBs is not equivalent to a diagnosis of MS

      Topic

      Neurology: MS

      Question 10 top

      Question 11 top

      Question 12 top Download PDF

      A 35-year-old woman with hypertrophic cardiomyopathy presents with chest pain and palpitations. Her heart rate is 155/minute and irregular, and her blood pressure is 130/80 mmHg.

      What is the most appropriate initial therapy?
      A. Beta-adrenergic blocker.
      B. Nitroglycerine.
      C. Amiodarone.
      D. Frusemide.
      E. Digoxin

      Answer: A
      In terms of this question the key features are:

      1. Patient has hypertrophic cardiomyopathy and is symptomatic
      2. She has a tachyarrhythmia
      3. Her blood pressure is reasonable
      4. She’s young

      1. Patient has hypertrophic cardiomyopathy and is symptomatic:

      • Aim of treatment is to relieve symptoms
      • And as no pharmacological therapy alters natural course you don’t treat the asymptomatic
      • Treatment options:
          • β blocker
          • verapamil
          • disopyramide
        • Methods of action

      β blocker

      Verapamil

      disopyramide

      • ↓ HR at rest and exercise leading to improved LV filling and ↓ outflow obstruction
      • Negative inotropes ↓ outflow obstruction
      • ↓ myocardial oxygen consumption improves chest pain

       

      • ↓ HR at rest and exercise leading to improved LV filling and ↓ outflow obstruction
      • Negative inotropes  ↓ outflow obstruction
      • Improves microvascular function  improves chest pain

       

      Anti-arrhythmic with negative inotropic properties
      Decreases subaortic pressure gradient

      BUT needs to be used w β blocker bc of effect on AV node conduction

      • β blocker and verapamil are first line
      • you can use either but some clinicians favour β blocker bc causes less vasodilation so less chance of worsening outflow obstruction
      • if one doesn’t work you can switch to the other
      • start low and uptitrate to symptom relief or side effects
      • if symptoms persist you can use β blocker + disopyramide

      Medications to avoid or use with caution:

      • Vasodilators:
      • Nifedipine, nitroglycerin, ACE-I, AR2B ↓ peripheral resistance
      • ↑ outflow obstruction and filling pressures
      • à hypotension and worsening heart failure
      • Diuretics:
      • Reduce preload à ↓ LV filling and smaller LV chamber and ↑ outflow obstruction

      **so answers B and D are wrong

      2. She has a tachyarrhythmia

      • Tachyarrhythmias are a big issue in HCM
      • Pts with HCM are prone to both atrial and ventricular arrhythmias
      • incidence increases with age
      • Most are benign and asymptomatic
      • but can precipitate hemodynamic collapse and sudden cardiac death
      • Cause problems for 2 reasons:
            1. Organized atrial contraction (ie, "atrial kick") contributes to left ventricular filling in pts with diastolic dysfunction and atrial contraction is lost during AF.
            2. Rapid ventricular rates reduce diastolic filling time, further impairing LV filling esp in diastolic dysfunction.

      ***degree of diastolic dysfunction impacts the ability to tolerate the tachyarrhythmia

      • There’s an association between AF and progressive HF symptoms, mortality, and stroke
      • So an aggressive approach to the maintenance of sinus rhythm is preferred

       

      • The decision needs to be made bw rhythm and rate control and that depends on whether patient is suitable for DCR and their age

      Rhythm control:

      • No recommended anti-arrhythmic by the 2006 ACC/AHA guidelines BUT amiodarone is probably the most effective

      Rate control:

      • As there’s a lack of controlled data showing benefit for maintaining sinus rhythm plus the complications assoc with some anti-arrhythmics rate control is often chosen esp in asymptomatic patients
      • Digoxin should be avoided as it is a positive inotrope and exacerbates HF symptoms and in those with preserved systolic function can worsen outflow obstruction

      *** so answer E is also wrong

      3. She’s young

      • At this point your left with β blocker and amiodarone
      • And whilst amiodarone would appear to be indicated I think her age is what makes β blocker the most appropriate

      Topic

      Cardiology: Cardiomyopathy

      Question 13 top

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      Question 19 top Download PDF

      A 19-year-old woman presents with recent-onset of right leg swelling and pleuritic chest pain and is found to have iliofemoral thrombosis on Doppler ultrasound examination. Results of a ventilation-perfusion lung scan indicate a high probability for pulmonary emboli. She had been taking the oral contraceptive pill for the last three years but has now ceased. She is a non-smoker. There is no significant medical history and no known family history of venous thromboembolism.
      Which one of the following investigations for an underlying hypercoagulable state is most likely to be affected by the presence of the extensive thrombosis?
      A. Antiphospholipid antibody screen.
      B. Antithrombin level.
      C. Factor V and prothrombin genotype assessment.
      D. Activated partial thromboplastin time (APTT).
      E. Full blood count including blood film.

      Answer :B

       

      Effect of

      Investigation

      Acute thrombosis

      Heparin

      Warfarin

      Antiphospholipid antibody screen

      No effect

      No effect

      No effect

      Antithrombin level

      decrease

      decrease

      Can increase

      Factor V genotype

      No effect

      No effect

      No effect

      Prothrombin genotype

      No effect

      No effect

      No effect

      APTT

      No effect

      increase

      No effect

      FBC

      No effect

      No effect

      No effect

      Protein S

      Can decrease

      No effect

      decrease (so can’t measure)

      Protein C

      Can decrease

      No effect

      decrease(so can’t measure)

      Lupus anticoagulant

      No change

      Can’t measure

      False positive possible

      Topic

      Haematology: thrombosis question repeated 2003 paper one question 64

      Question 20 top

      Question 21 top Download PDF

      T lymphocytes expressing both CD4 and CD8 on the cell surface are most likely to be found in which one of the following anatomical locations in healthy individuals?
      A. Bone marrow.
      B. Thymus.
      C. Peripheral blood.
      D. Lymph nodes.
      E. Spleen.

      Answer: B

      T cell formation:

      • T cell precursors are formed in bone marrow
      • They then travel via the periphery to the Thymus where they differentiate into functional T lymphocytes

      Role of the thymus:

      1. Produce sufficient T cells each with different T cell receptor (TCR) so that there are at least some cells potentially specific for each foreign antigen
      2. Select T cells for survival so as to minimise autoimmunity

      **T cell development within the thymus is independent of antigens

      • Once maturation in the thymus occurs T cells have only one antigen receptor (TCR)
      • This TCR is expressed on a T cell that has CD4+ and CD8+ on its surface (double positive thymocyte)
      • This receptor is then used to select the T cells that will go on to mature and those that will be destroyed
      • Those with receptors that bind strongly to MHC molecules and thus have the potential to recognise self a/g  (and cause autoimmunity) are destroyed by apoptosis (negative selection)
      • Those with receptors that bind weakly to MHC molecules are selected (positive selection)
      • T cells which survive selection mature into different T cells (T helper or cytotoxic)
      • Thus the surviving population reacts to peptides in the context of self MHC molecules but cannot react productively to self antigen
      • 95% of T cells produced are destroyed bc of:
      1. Failure to form a functional TCR
      2. Lack of positive selection
      3. Negative selection

      Bone Marrow:

      • Only contains T cell precursors
      • Also where B cells are formed and mature

      Thymus:

      • T cell precursors travel there and differentiated
      • Only point where CD4 and CD8 on same cell as it is yet to completely differentiate

      Peripheral Blood, Lymph nodes, Spleen

      • Contain differentiated T cells – ie CD4 or CD8 T cells

      Topic

      Haematology: Haemopoiesis

      Question 22 top

      Question 23 top

      Question 24 top download PDF

      The picture below shows a computed tomography (CT) scan of the heart.

       

      Which one of the following is the most likely diagnosis?
      A. Metastatic tumour in the pericardium. 
      B. Left atrial myxoma.
      C. Ruptured myocardial papilla.
      D. Cor triatriatum.
      E. St. Jude mitral valve prosthesis.

      This is a normal CT of the heart :

      • The abnormality is in the left atrium
      • There is no metal artefact (not E)
      • As it is a mass rather than a fibrous band the most likely diagnosis is myxoma

      A. Metastatic tumour in the pericardium

      Metastatic involvement usually assoc with pericardial effusion + irregular pericardium

      • Metastatic involvement of the heart is relatively common
      • Can arise from
      • hematogenous metastases
      • direct invasion from the mediastinum
      • tumor growth into the vena cava and extension into the right atrium
      • Malignant melanoma is common source of mets
      • Others associated: lung, breast, soft tissue sarcomas, renal, esophageal, hepatocellular, and thyroid ca
      • high prevalence with leukemia and lymphoma.

       

      B. Left atrial myxoma

      Atrial myxomas

      • most common primary heart tumors (40-50%)
      • most found in LA 75-85%; 25% RA
      • Most are benign
      • 2D echocardiography is the diagnostic procedure of choice
      • Most cases are sporadic, 10% are familial - autosomal dominantly
      • Familial form: 50% have multiple tumours more frequently in ventricle (13% vs 2% in sporadic cases).
      • Myxomas are plypoid, round or oval
      • most common site of attachment is border of the fossa ovalis in the left atrium
      • mobility depends upon the extent of attachment to the interatrial septum + length of stalk
      • Symptoms are produced by mechanical interference with cardiac function or embolization.
      • Being intravascular and friable, myxomas account for most cases of tumor embolism
      • Embolism occurs in 30-40% of pts
      • Site of embolism depends upon the location (LA or RA) and presence of intracardiac shunt.

      C. Ruptured myocardial papilla.

      • papillary muscles attach to the lower portion of the interior wall of the ventricles
      • connect to the chordae tendineae, which attach to the tricuspid valve in the right ventricle and the mitral valve in the left ventricle
      • contraction of the papillary muscles opens these valves
      • when the papillary muscles relax, the valves close.
      • Rupture of papillary muscles leads to mitral regurg or tricuspid regurg

       

      On TTE

      • There will be evidence of a flail mitral leaflet
      • ruptured head is seen in the left ventricle and usually prolapses back into the left atrium 

       D.  Cor triatriatum.

      • Rare congenital anomaly
      • left atrium (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is divided into 2 parts by a fold of tissue, a membrane, or a fibromuscular band

      Cor triatriatum sinistrum

      • Clinical manifestations depend upon the size of the opening in the septum and the presence of assoc congenital cardiac defects
      • In most, opening is severely restrictive
      • Symptoms are similar to those of severe MS
      • In the adult, sympt often delayed due to the presence of a large opening
      • Transition from asymptomatic to symptomatic in the adult is due to fibrosis and calcification of the orifice in the accessory membrane or development of mitral regurgitation and/or atrial fibrillation.
      • Symptoms include the following:
      • Exertional dyspnea
      • Effort intolerance and easy fatigability
      • Hemoptysis
      • Orthopnea
      • Palpitation (atrial fibrillation)
      • systemic throboembolism - esp in AF and /or restrictive orifice, as both promote thrombus formation in the left atrium

      E. St. Jude mitral valve prosthesis.

        • bileaflet aortic valve
        • most widely used valve
        • St Jude occluding mechanism consists of two semicircular leaflets with small ears that pivot in butterfly-shaped recesses in the

        Topic

        Cardiology: I cannot find an appropriate spot for this

         

         

        Question 25 top Download PDF

        Vertigo which occurs with neck extension is most likely due to:
        A. cervical spondylosis.
        B. benign paroxysmal positional vertigo.
        C. kinking of the vertebral artery.
        D. endolymphatic hydrops.
        E. Chiari 1 malformation.

        Answer: B

        Vertigo precipitated by movement is characteristic of:

        1. Benign Paroxysmal Positional Vertigo
        2. Chiari 1 malformation
        3. Kinking of the vertebral arteries

        Vertigo is not a symptom of cervical spondylosis

        The vertigo due to endolymphatic hydrops (Meniere’s Disease) is spontaneous.

        • Benign Paroxysmal Positional Vertigo
        • Is the commonest cause of vertigo diagnosed
        • Due to calcium debris in the posterior semicircular canal
        • Brief spinning sensation due to movement or tilting of the head
        • Last seconds up to a minute
        • Assoc with nauea but no vomiting
        • No ear pain, tinnitus or hearing loss
        • 50-80% have a positive hall pike
        • Chiari I malformation
        • Extension of cerebellar tonsils below the foramen magnum
        • Usually congenital (but only type of Chiari malformation that can be acquired)
        • may be asympt or assoc with headache or neck pain, weakness with long tract signs, dysphagia, and other lower cranial nerve abn
        • Vertigo and gait imbalance are common
        • Vertigo is often positionally induced esp by neck extension
        • Vertiginous symptoms are generally mild and often resolve with alteration of head position.
        • Often assoc with downbeating nystagmus
        • Diagnosis is confirmed with saggital MRI.
        • Surgical decompression may be required and is usually successful
        • Kinking of the vertebral arteries
        • Can cause vertigo
        • It usually occurs as a result of extrinsic compression most often in the setting of atlanto axial rotation
        • I don’t think its common

        Topic

        Neurology: Dizziness

        Question 26 top

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        Question 30 top

        Question 31 top Download PDF

        A 32-year-old woman, who has recently migrated from India, is breastfeeding her third child and presents with lethargy and a history of recurrent chest infection. She has a vegetarian diet. Physical examination shows her to be anaemic with no site of blood loss clinically evident and no other abnormalities.
        Investigations show:
        Full blood count
        haemoglobin 64 g/L [120-155]
        mean corpuscular volume (MCV) 68 fL [80-95]
        white cell count 7.4 x 109/L [3.5-9.5] ; differential normal
        platelet count 412 x 109/L [130-330]
        Blood film is shown below.

        With respect to the patient’s anaemia, which one of the following laboratory results has the most diagnostic value?
        A. A lower than normal serum iron level.
        B. A lower than normal serum ferritin level.
        C. A higher than normal serum transferrin level.
        D. A negative urinary haemosiderin test.
        E. A normal plasma haemoglobin A2 level.

        Answer: B

        • A lower than normal ferritin indicates Fe deficiency anaemia as there are no other clinical states which result in low ferritin.
        • Low serum iron occurs in anaemia of chronic disease and iron deficiency
        • High transferrin can be due to iron deficiency but also occurs in pregnancy and with the OCP (second most accurate investigation of Fe deficiency)
        • The red cell indices describe a Microcytic (MCV 68) anaemia (Hb 64)
        • The blood film also shows this but also shows hypochromia, and occasional pencil shaped cells poikilocytes

        Normal blood film

          • platelets (black arrows)
          • normal lymphocyte (blue arrow)
          • The red cells are of relatively uniform size and shape.
          • The diameter of the normal red cell should approximate that of the nucleus of the small lymphocyte; Central pallor (red arrow) should equal one-third of its diameter.

          • pale small red cells with just a scant rim of pink haemoglobin
          • anisositicis – heterogenous cell size
          • occasional "pencil" shaped cells are also present.
          • Normal red cells are similar in size to the nucleus of a small lymphocyte; thus, many microcytic cells are present in this smear.

          MICROCYTIC ANAEMIA
          3 most common causes of microcytosis are:

          1. iron deficiency
          2. alpha or beta thalassemia minor
          3. anaemia of chronic disease (less commonly)

          IRON DEFICIENCY
          Causes

          • Blood loss - gastrointestinal or menstrual
          • Iron malabsorption
          • Chronic intravascular haemolysis with iron loss in urine

          Blood film

          • Classic picture: hypochromic microcytic anaemia
          • Also caused by:           Thalassaemia

          Anaemia of chronic disease
          Sideroblastic anaemias
          Iron deficiency:

          • Anisocytosis – heterogenous erythrocyte size
          • Poikilocytosis – irregularly shaped erythrocytes
          • Target cells
          • Thrombocytosis

          Thalassaemia:

          • Basophilic stippling
          • Target cells
          • Polychromasia (dark staining reticulocytes)
          • Sideroblastic anaemia
          • Dimorphic cells (large and small)

          Iron studies – trying to estimate the marrow stores


          Serum iron

          LOW

          TIBC/transferrin

          HIGH

          Saturation 
          (SI/TIBC x100)

          LOW

          Ferritin

          LOW

          Serum iron

          • Low serum iron is not specific
          • Occurs also in anaemia of chronic disease

          Ferritin

          • Excellent indicator of iron stores in otherwise healthy adults
          • Gold standard if you ignore bone marrow biopsy
          • For ferritin in range 20 – 300 ng/mL, there is a direct relationship between ferritin concentration and iron stores [iron stores (mg) = (8 to 10) ´ ferritin (ng/mL)]
          • There is no clinical situation other than iron deficiency in which ferritin levels are low

          Ferritin cutoff

          Sensitivity

          Specificity

          10-15

          59%

          99%

          30

          92%

          98%

          41

          98%

          98%

          Pregnancy

          • Serum ferritin is the most useful measure in pregnancy
          • This is because transferrin is often elevated without iron deficiency

          Inflammatory states

          • Is an acute phase reactant (IL-1 and TNF increase synthesis)
          • Levels increase in liver disease, infection, inflammation and malignancy
          • ↑ usually three fold– deficient if ferritin/3 is < 20 eg. RA

          Transferrin(TIBC)

          • Transferrin is second most accurate measure
          • Problem is in pregnancy and OCP result in an ↑ transferrin which can result in low saturation but not be reflective of Fe deficiency

          NB:          Urinary hemosiderin – is used as a measure of intravascular hemolysis
          Increased levels of Hb A2 – are found in beta thalassemia

           

          Topic

          Haematology: Anaemia

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          Question 39 top Downlod PDF

          Which one of the following is the strongest independent risk factor for stroke?
          A. Hypertension.
          B. Cigarette smoking.
          C. Physical inactivity.
          D. Age.
          E. Hypercholesterolaemia.

          Answer: D

          Age is the strongest independent risk factor for stroke
          For each decade after 50yo the risk of stroke doubles

           

           

           

           

          Modifiable Risk Factors:


          HYPERTENSION

          Most significant modifiable risk factor for both cerebral infarction and intracerebral hemorrhage
          Relationship between BP and CV risk is “continuous, consistent, and independent of other risk factors.”
          The higher the blood pressure, the greater the stroke risk
          Antihypertensive therapy is associated with a 35% to 44% ò in incidence of stroke

          CIGARETTE SMOKING

          2x risk of ischemic stroke
          2- to 4-fold increased risk for hemorrhagic stroke
          cessation is associated with a rapid reduction in the risk of stroke and other CV events to a level that approaches but does not reach that of never smoker

          DIABETES

          Tight control of BP in diabetics ò stroke incidence
          BUT tight glycaemic control does not
          Treatment w statin to lower stroke risk is also recommended

          AF

          3-4x increase risk
          Strokes due to AF are large and disabling
          Rhythm control does not appear to reduce stroke rates
          Antithrombotic therapies remain the mainstay for stroke prevention.
          Risk reduction 60% with warfarin and 20% with aspirin

          MECHANICAL VALVE

          All need anticoagulation
          Rate of thromboembolis

          • w/o anticoag 4.4 per 100 pt years
          • with antiplatelets 2.2 per 100 pt years
          • with warfarin 1 per 100 pt years

          highest risk for stroke is valvular heart disease + AF

          HYPERCHOLESTEROLAEMIA

          Give statin to:

          • pts w/o CVA and ↑ TC or non–HDL and hypertriglyceridemia
          • pts w known CAD and/or high-risk HTN even if LDL is normal
          • diabetic patients

          Give gemfibrozil to:

          • pts w known CAD and low HDL

          CAROTID STENOSIS

          Prophylactic carotid for high-grade asymptomatic carotid stenosis

          HRT

          Womens health initiative showed ↑ risk of stroke

          OSA

          Thought to be a risk factor for stroke
          Successful treatment reduces blood pressure

          HYPERCOAGULABILITY

          Most throbophilias are assoc with venous thrombosis not CVA
          Antiphospholipid antibody most assocw arterial thrombosis

           

           

          Non-modifiable risk factors for stroke:


          AGE

          Risk of stroke doubles each successive decade after 55 years

          GENDER

          More prevalent in men than women
          Men also have a higher age specific incidence except in 35-44yo and >85yo

          LOW BIRTH WEIGHT

          Stroke mortality is higher among those with LBW

          ETHNICITY

          Higher incidence in African Americans and Hispanics and some Asian groups

          GENETICS

          Maternal or paternal history of stroke is assoc with increased risk
          Risk could be mediated through a variety of mechanisms including
          (1) genetic heritability of stroke risk factors
          (2) the inheritance of susceptibility to the effects of such risk factors
          (3) familial sharing of cultural/environmental and lifestyle factors
          (4) the interaction between genetic and environmental factors

           

           

          Treatment recommendations for AF Downloaded from stroke.ahajournals.org

          Topic

          Neurology: Stroke

           

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          Question 45 top Download PDF

          A 48-year-old previously well man is receiving a transfusion of four units of packed red cell concentrate via a peripheral intravenous line after presenting with melaena secondary to a bleeding duodenal ulcer. He has not been previously transfused. Admission biochemistry (including urea, electrolytes and creatinine) is normal and pre-transfusion blood counts are normal apart from anaemia (haemoglobin 64 g/L [135-170]). Less than five minutes after transfusion of the third unit of blood is commenced, he complains of feeling very unwell and abruptly develops fever, chills, rigors and profound hypotension.

          In the absence of ABO, Rhesus or minor blood group donor-recipient incompatibility, the most likely diagnosis is:

          A. bacterial contamination of the transfused blood.
          B. transfusion-associated graft-versus-host disease.
          C. electrolyte disturbance.
          D. citrate toxicity.


          E. reaction to plasticiser in infusion bag.

          Answer: A

          Differential Diagnoses for febrile reaction to transfusion:

            • Febrile non-hemolytic transfusion reaction
            • Acute hemolytic transfusion reaction
            • Urticarial reaction
            • Fever due to underlying condition
            • Transfusion transmitted bacterial infection

          Bacterial contamination of transfused blood:

          • 2 most common causes of transfusion associated death are:
            • Acute Haemolytic Transfusion Reactition (ABO mismatch)
            • Transfusion Transmitted Bacterial Infection
          • Can develop fevers and chills which can progress to septic shock and DIC
          • Can occur abruptly within minutes or up to hours
          • Onset of symptoms is often sudden and fulminant
          • Which distinguishes it from febrile non-hemolytic transfusion reaction
          • Infections related to gram negatives are due to infusion of toxins

           

          • Most bacteria do not grow well in cold temps
          • More common to get transmission of bacteria through platelet transfusion
          • Incidence:
            • 1 in 5000 platelet transfusions (stored at room temp)
            • 1 in 30,000 PRBC transfusion (stored at 4C)
          • Important factor is the duration of storage: ↓ storage time ↓ rate of infection

           

          Common microbiology:

          • As RBCs are stored at 4 degrees more commonly bacteria that can multiply at cold temps
          • eg Yersinia, pseudomonas
          • Platelet contamination is more commonly gram positives esp skin contaminants

          Approach to transfusion related fever:

            • stop transfusion
            • resuscitate
            • get blood from other arm
            • check for clerical error (?ABO mismatch)
            • if suspected bacterial contamination à broad spectrum antibiotics
            • alert blood bank and back for checking

           TYPES OF TRANSFUSION REACTIONS

          • Adverse reactions occur in 1-6% of all blood transfusions
          • more frequent (10%) in pts with hematologic and oncologic diseases

          Divided into

          • Immunolgically Mediated
          • Non-immunologically Mediated
          • Infectious complications

           

          Immunologically Mediated Reactions

          • Acute Hemolytic Reaction
          • Delayed hemolytic reaction
          • Febrile Non Hemolytic Reaction
          • Urticarial Reactions
          • Anaphylactic reactions
          • Graft v Host Disease
          • Transfusion related acute lung injury
          • Post-transfusion purpura

          Non-Immunologically Mediated Reactions

          • Fluid overload
          • Hypothermia
          • Electrolyte Toxicity
            • Hyperkalaemia
            • Citrate toxictity – hypocalcaemia
          • Iron overload

          Infectious Complications:

            • Viral infections
            • Hep C
            • HIV
            • Hep B
            • CMV
            • Parvovirus B19
            • Bacterial contamination

            Topic

            Haematology: Tranfusion Repeat Question 2002 paper one question 57

             

            Question 46 top

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            Question 48 top Download PDF

            Which one of the following findings during a stress exercise ECG test is most predictive of angiographically significant multivessel or left main coronary artery disease?

            A. Late-onset of ST-segment depression.
            B. Return to normal of ST-segment changes early in recovery phase.
            C. ST-segment elevation in lead aVR.
            D. Multifocal premature ventricular contractions.
            E. Failure to increase systolic blood pressure by at least 10 mmHg

            Answer: E

            Stress exercise ECG test indirectly assesses adequacy of supply in periods of increased demand

            Sequence of events in ischaemia:

            Regional wall motion abnormalities 10-30sec

            Decrease in ejection fraction

            Increase in end diastolic pressure

            ST segment abnormalities without pain

            Angina

            This sequence of events explains why other cardiac imaging is more sensitive than ECG testing

            Estimation of prognosis:
            Factors predicting an ↑ risk of adverse outcome in pts with CHD:

              Poor exercise capacity < 5METS

              Exercise induced angina (esp if exercise limiting or occurs at low workload)

              Abnormal low peak systolic BP (<130mmHg) or fall in systolic BP below baseline

              Chronotropic incompetence

            ECG findings that predict ↑ risk of adverse outcome:

            ≥ 1mm down slopping or flat ST depression

            ≥ 2mm ischaemic ST depression at low workload (stage 2 or less or ≤130bpm)

            Early onset (stage 1) or prolonged duration (>5min) ST depression

            Multi leads (>5) with ST depression

            Ventricular couplets or tachycardia at low workload or in recovery

            SR/HR slope (6microV/beat per min)

             Answers:

            A. Late onset ST depression is normally seen in prolonged exercise probably due to atrial repolarisation extending into the QRS.

            Much more significant is early onset ST depression in predicting severe coronary artery disease

            B. ST changes returning to normal is obviously good but ?significance.

            C. ST elevation is uncommon in exercise testing

            When it occurs it is commonly seen in leads with pathological Q waves

            In this situation the ST elevation is due to wall motion abnormalities rather than ischaemia 

            It can occur in:

              Prinzmetal angina

              In multivessel disease where one primary vessel is leading to the ischaemia.

              In that case there is ST depression in V5 and the ST elevation indicates the  single vessel most likely causing the ischaemia.

            ST elevation is not pathological if seen in V1 or avR

            D. PVC’s occur in about 7-20% of people having exercise testing. 

            It is not proven to have an association with CAD but potentially be an indicator of ventricular arrhythmia development risk and is an independent predictor of mortality.

              E. Failure to increase sBP or in fact a fall in sBP is one of the poor predictive outcomes

              generally indicates severe coronary artery disease.

              Topic

              Cardiology: stress exercise testing

               

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