Q1

What is a paraneoplastic syndrome?

  • A complex of symptoms that cannot be readily explained by the local or distant spread of a tumour or by elaboration of hormones from the tissue in which the tumour arose

Pass criteria:

  • Bold to pass

What are the main types of paraneolastic syndromes?

  • Endocrinopathies
    • Cushing – Small Cell Ca lung (ACTH)
    • SIADH – Small Cell Ca lung, intracranial (ADH)
    • Hypercalcemia – Squamous Cell Ca lung, breast (parathyroid like hormones, TNF, TGF, IL-1)
    • Carcinoid – bronchial adenoma, ca pancreas and stomach – serotonin/bradykinin)
    • Polycythemia – Renal (EPO)
  • Nerve and Muscle Syndromes
    • Myasthenia (bronchogenic Ca – immune mechanism)
    • CNS/neuro (breast)
  • Dermatological
    • Acanthosis Nigricans (gastric, lung, uterine)
    • Dermatomyositis (bronchogenic. Breast)
  • HPOA
    • bronchogenic

Pass Criteria:

  • Endocrinopathies with at least 2 examples and at least one other to pass.

What is the cause of cachexia in cancer?

  • Not generally understood
  • Anorexia
  • Elevated BMR
  • humoral factors – TNF, cytokines,
  • Other tumour produced factors

Q2

What are the pathological consequences of thiamine deficiency?

  • Polyneuropathy (Dry beriberi):
    • symmetric peripheral polyneuropathy
    • myelin degeneration leading to axonal disruption in motor and sensory fibres, and reflex arcs
  • Cardiovascular consequences (Wet beriberi)
    • peripheral vasodilation
    • AV shunting
    • High output failure
    • Cardiac chambers may dilate
  • Wernicke-Korsakoff syndrome
    • Wernicke’s: opthalmoplegia, nystagmus, ataxia, higher centre dysfunction
    • Korsakoff’s:  permanent impairment of remote recall, confabulation

Pass criteria:

  • 2 consequences with some details to pass

In what areas of the CNS are lesions observed in Wernicke-Korsakoff?

  • Mamillary bodies
  • Periventricular region of thalamus
  • Floor 4th ventricle
  • Anterior cerebellum

Pass Criteria:

  • At least 1 site

Q3

What is the aetiology of iron deficiency anaemia?

  • Chronic blood loss – GIT, menorrhagia
  • Increased requirement – pregnancy
  • Dietary deficiency – vegetarians
  • Impaired absorption – celiac

Pass criteria:

  • Bold PLUS 1 other

What are the laboratory findings in iron deficiency anaemia?

  • Microcytic hypochromic anaemia (low Hb)
  • Low S. Fe levels
  • Low S. Ferritin levels (correlates well with body iron stores)
  • High TIBC (high transferrin levels)
  • Low Transferrin saturation levels

What are the clinical features of iron deficiency anaemia?

  • General – pallor, weakness, lethargy, fatigue, SOBOE, angina
  • Features of blood loss – GI, menorrhagia
  • Specific features – koilonychia, alopecia, glossitis, pica

Pass criteria:

  • At least 5 from 2 groups

Q3

Describe the organ system effects of lead poisoning.
How does lead effect the CNS? What other systems does it effect?

  • CNS: encephalopathy including headache, dizziness, memory disturbance even coma, impaired CNS development in foetus and infants
  • PNS: peripheral neuropathy (impaired conduction)
  • Haematological:  microcytic hypochromic anaemia, haemolysis, characteristic basophilic stippling of red cells
  • Renal: renal tubular injury
  • CVS: hypertension
  • Genitourinary:  male infertility, failed ovum implantation

Pass criteria:

  • 3 systems with some details to pass

With regard to lead poisoning, what are the toxic mechanisms that operate?

  • High affinity for sulfhydryl groups: binds to gamma-aminilevuline acid dehydratase and ferroketolase, involved in heme synthesis
  • Competition with calcium ions: interferes with nerve transmission and brain development
  • Inhibition of membrane-associated enzymes including NA-K ion pumps

Q5

By what mechanism does smoking contribute to emphysema?

  • Emphysema is consequence of high protease (elastase) activity with low anti-protease (elastase) activity.
  • Smoke
    • Increases neutrophils + macrophages in alveoli
    • Release of elastase from neutros
    • Enhanced elastolytic activity in macrophages
    • Inhibition of alpha 1 AntiTrypsin (oxidants in smoke, oxygen free radicals from neutros).

What cancers can smoking predispose to?

  • Oropharyx, larynx, lung, oesophagus, stomach, pancreas, bladder

Q6

What are the major pathological consequences of IV drug abuse?

  • Thrombo phlebitis.
  • Sepsis to injection site, lungs, heart valves, bones.
  • Viral inoculation – Hepatitides, HIV;
  • ARDS

What are the features of IVDU endocarditis?

  • 10% of hospitalised addicts.
  • Distinctive form involving R valves, esp. tricuspid;
  • Most are staph aureus; fungi and a multitude of others do occur

Q7

Describe the steps involved in tumour cell invasion of the extracellular matrix.
Prompt: 'Detachment is the first step…'

1.            Detachment (`loosening up’) of the tumour cells from each other, with breaking of intercellular bonds

2.            Attachment to extracellular matrix (ECM) components, via laminin and fibronectin receptors

3.            Degradation of ECM, via type IV coilagenase and plasminogen activator, creating passageways

4.            Migration of tumour cells, which may then lead to vascular dissemination

Pass:  Accept at least 3 of 4 bolded words (or a similar explanation) for a pass.

Describe possible mechanisms that influence the distribution of metastases.
Prompt: 'Chemokines have an important role…'

1.            Tumour cell adhesion molecules ligands preferentially expressed on target organ cells

2.            Chemokines for target tissues

3.            Chemoattractants from target organs


Q8

What is the function of Vitamin K?

Required co-factor for a liver microsomal carboxylase which carboxylates a glutamate residue in Factors VII, IX, X & prothrombin (PLUS Proteins C & S and a few others)

Necessary for binding calcium and thus functional activity of the proteins

Pass: 3 of 4

What are the causes of Vitamin K deficiency?

  1. Fat malabsorption syndrome
  2. Destruction of endogenous Vitamin K-synthesizing flora in the gut by broad spectrum antibiotics
  3. Neonates (small liver reserves, no bacterial flora and low Vitamin K in breast milk)
  4. Diffuse liver disease (hepatocyte dysfunction interferes with synthesis of Vitamin K dependent factors)

Pass: Should know all the clotting factors and Protein C & S


Q9

How do tumour cells metasise?
Prompt: 'at a cellular level'

  1. Invasion of extracellular matrix

clonal expansion, growth, diversification, angiogenesis

invasion of ECM

metastatic subcfone

adhesion to and invasion of BM

passage through ECM

intravasation (blood/lymphatic)

 

  1. vascular dissemination and hominginteraction with host lymphoid cells

tumour cell embolus…platelet tumour aggregates

adhesion to BM

extravasation

metastatic deposit

angiogenesis

growth

Why do some tumours metatasise to sites other than their natural blood and lymphatic drainage areas?

a)            adhesion molecules whose ligands expressed preferentially on target organs

b)            chemokine receptors for target chemokines highly expressed in some organs

c)            target tissue may be unpermissive environment (eg skeletal mm)


Q10

What is a paraneoplastic syndrome?

Symptom complex in cancer-bearing patient not readily explained by tumour spread local or distant, or by hormones produced by the tumour tissue itself.

 

What are the mechanisms by which they can occur?

–              Ectopic hormone production* and give example

–              Immunologic/autoimmune Eaton-Lambert, dermatomyositis

–              Tumour antigens

 

Examples:

Cushings syndrome (ACTH) with small cell lung /pancreas/neural cas;

hvpercalcemia (PTH peptide) with sq lung /breast/renal/ leuk/ovarian;

SIADH small cell lung /brain; hypoglycemia, carcinoid,

Myasthenia-like,

Acanthosis nigrans, Hypertrophic osteoarthropathv, thrombosis

 


Q11

How are thermal burns classified?

  • According to depth of injury:
    • Superficial – confined to epidermis
    • Partial thickness – extends to dermis
    • Full thickness – involves subcutaneous tissue

Pass Criteria:

  • Bold to pass

What are the potential complications of thermal burns?

  • Early
    • Hypovolaemic shock (especially with >20% BSA)
    • Compartment syndrome (circumferential lower limb burn)
    • Associated injuries (e.g. inhalational burn, CO poisoning)
    • Airway compromise
    • Hypermetabolic state
  • Late
    • Infection/sepsis (Pseudomonas)
    • ARDS
    • Multi-organ failure
    • Skin grafting, scarring/cosmetic
    • Psychological

Pass Criteria:

  • 2 early
  • 2 late

How do you determine the extent of burns?

  • TBSA calculation notoriously inaccurate. Does not include superficial burns
  • Wallace “rule of nines”
  • Lund & Browder diagram

Pass Criteria:

  • Mention 1 method

 


Q11

An 80 year old woman is transferred to your ED following a motor vehicle accident 12 hours ago, where she sustained serious chest injuries. She has multiple wounds oozing blood due to Disseminated Intravascular Coagulation (DIC). On a full blood count and coagulation profile, what would you expect to find?

  • Decreased Hb (MAHA – microangiopathic haemolytic anaemia)
  • Increased WCC
  • Decreased platelets
  • Decreased fibrinogen
  • Increased PT/INR
  • Increased a/PTT
  • Increased fibrin degradation products

Pass Criteria:

  • Bold to pass

What are the pathological consequences of DIC?

  • DIC – major trauma releases tissue thromboplastins. Both sides of clotting cascade are activated.
  • 2 major consequences
    • Deposition of fibrin within microcirculation leading to ischaemia/microthrombosis of vulnerable organs
    • Consumptive coagulopathy – platelets and clotting factors leading to a bleeding diathesis

Pass Criteria:

  • 3/3 bold to pass

What are the causes of DIC?

  • Obstetric
    • Fetal Death In Utero
    • Amniotic fluid embolism
    • Pre-eclampsia
  • Sepsis
  • Malignancy
    • Acute promyelocytic leukaemia
    • Adenoma of lung, pancreas, stomach and colon
  • Trauma
    • Multi/burns/environmental/snakebite

Pass Criteria:

  • Must get 3 categories

 


Q12

What is the definition of a neoplasm?

  1. Abnormal growth of a tissue
  2. Growth exceeds and is uncoordinated with that of the original tissue
  3. Growth continues in the absence of stimuli which evoked the change
  • (Preys on host and serves no purpose)

Pass Criteria:

  • Must get gist of all 3

How may a malignant tumour affect the 'host'?

PROMPT – What is meant by paraneoplastic syndrome? Give examples of paraneoplastic endocrinopathies.

  • Local and metastatic direct effects
    • Pressure
    • Bleeding
    • Ulceration
    • Rupture
    • Infarction
  • Cachexia
  • Hormonal
  • Paraneoplastic
    • Endocrinopathy with 3 examples (Cushing’s, SIADH, Ca++ up, hypoglycaemia, Carcinoid syndrome, polycythaemia)
    • Nerve and muscle – myasthenia
    • Skin – acanthosis nigricans, dermatomyositis
    • Bone – HPOA and clubbing
    • Blood/vascular – anaemia, venous thrombosis

Pass Criteria:

  • 3 of 4 bold to pass
  • 3 examples of paraneoplastic syndrome

 


Q13

What is sickle cell disease?

PROMPT – Is it congenital or acquired?

  • Hereditary blood disorder
  • Haemoglobinopathy

Pass Criteria:

  • Bold to pass

What are the major pathological manifestations of sickle cell disease?

  • Haemolysis/Haemolytic anaemia
  • Microvascular occlusions (crises/tissue ischaemia = severe pain in affected organs e.g. bones, lungs, liver, spleen)
  • Splenic enlargement, infarct and dysfunction (Increased susceptibility to infection – encapsulated organisms [e.g. strep pneumonia, haemophilus influenza])

Pass Criteria:

  • 2 of 3 to pass

In general how are haemolytic anaemias classified?

  • Inherited genetic defects
    • RBC membrane {Spherocytosis)
    • Enzyme deficiencies (G6PD)
    • Haemoglobinopathies (Thalassaemia, SIckle Cell Disease)
  • Antibody mediated destruction
    • Transfusion reactions
    • Autoimmune
  • Mechanical trauma
    • Microangiopathic haemolytic anaemias (HUS, DIC, TTP)
    • Cardiac valves
  • Infections of red cells
    • Malaria
  • Toxic
    • Envenomation

Pass Criteria:

  • 2 of 5 bold to pass

 


Q14

What are the sequence of events in haemostasis after a vascular injury?
Prompt: Is there any particular sequence to the events?

  • Vasoconstriction:
    • Arteriolar
    • Reflex neurogenic
    • Enhanced by endothelin
  • Primary haemostasis
    • Extracellular matrix exposed
    • Platelet adherence/activation
    • Platelet aggregates and forms plug
  • Secondary Haemostasis
    • Tissue factors exposed
    • Factor III
    • Thromboplastin
    • Factor VII
    • Platelet plug consolidated – thrombin/fibrin generated
  • Thrombus & antithrombotic effect
    • Fibrin polymerises to form permanent plug, tPA regulates

Pass Criteria:

  • Identify 3/4 steps of haemostasis (Bold) in correct sequence

What laboratory tests are used to assess the function of the different pathways of the coagulation cascade?
Prompt: Which one is vitamin K dependent?

  • Prothrombin time – extrinsic pathway
    • Factors VII, X, II, V, fibrinogen (including vit K dependent factors)
  • Partial thromboplastin time – intrinsic pathway
    • Factors XII, XI, IX, VIII, X, V, II, fibrinogen

Pass Criteria:

  • To pass identify test, what pathway it is testing and identify which one is vit K dependent

Q15

Coagulation Profile

What is the abnormality on this coagulation profile?

  • Delayed clot formation in both the extrinsic (PT/INR) and intrinsic (APTT) systems
  • Fibrinogen low
  • Consistent with a consumptive coagulopathy/DIC

Pass Criteria:

  • Must state coagulopathy / DIC

What could cause this?

  • Sepsis
  • Liver failure
  • Malignancy
  • Trauma
  • Envenoming (Brown/Tiger/Taipan)
  • etc

Pass Criteria:

  • One example of possible cause