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