Paper 1

Question 1

List six (6) human herpesviruses using their common names (using “HHV” numbers only if those
are used as common names), and state the main disease, if any, that they cause during acute
infection, and state which cancers, if any, they cause. Use the table below.

Answer 1

Herpesvirus name Main disease caused in acute infection Cancer caused (if any)
Herpes simplex 1 Oral herpes ulcers None
Herpes simplex 2 Genital herpes None
Varicella-Zoster Chickenpox/varicella None
Epstein Barr virus Infectious mononucleosis Lymphomas
Cytomegalovirus None / Infectious mono None
Herpes (HHV) 6* Roseola infantum None
Herpes (HHV) 7* None None
Herpes (HHV) 8 /
Kaposi’s sarcoma
associated herpesvirus
None Kaposi’s sarcoma

Question 2

Define the term opportunistic pathogen.

Answer 2

Organism that is able to cause infection only when the immune system is weakened.

Question 3

The patient is diagnosed with an invasive fungal infection. Aspergillus is isolated from multiple
cultures. State the most likely mode of infection and how it can be prevented.

Answer 3

Inhalation
Limit exposure to fungi in environment- filters in room, isolation, no flowers in room
Antifungal prophylaxis

Question 4

Name the drug most often used as empiric treatment for invasive fungal disease.

Answer 4

Amphotericin B

Question 5

Name (in full) the opportunistic organism that typically causes hypoxic pneumonia in HIV positive
and other severely immunocompromised patients that has been re-classified as being related to
fungi.

Answer 5

Pneumocystis jirovecii

Question 6

State the diagnosis. - ahem

Answer 6

Acute leukaemia

Question 7

Give a definition for your diagnosis. - AL

Answer 7

Acute leukaemia is the presence of at least 20 percent blasts in the blood or bone marrow

Question 8

List the cause of the patient’s clinical symptoms/signs.

Answer 8

Fatigue – Anaemia (1)
Epistaxis – Thrombocytopenia (1)
Persistent sore throat/Infection – Neutropenia

Question 9

Outline the mechanism of the pancytopenia.

Answer 9

Bone marrow infiltration leading to decreased production of blood cells (2)

Question 10

List four (4) other clinical signs you may see in a patient with thrombocytopenia.

Answer 10

Petechial haemorrhages, Purpura, oronasal bleeding, genitourinary bleeding, surgical bleeding (any 4)

Question 11

Compare and contrast the morphological features that would help you differentiate myeloid versus
lymphoid blasts.

Answer 11

Myeloid blasts (Auer rods, cytoplasmic granules) (1)
Lymphoid blasts (no Auer rods, no granules) (1)

Question 12

Name the two (2) cytochemical stains that you would request to confirm the myeloid nature of the
blasts.

Answer 12

Myeloperoxidase(MPO) and Sudan black stain positive in myeloid blasts and negative in lymphoid blasts

Question 13

Differentiate between acute leukemia and chronic leukemia in terms of onset and cell of origin.

Answer 13

Acute leukemia: Onset – rapid (within days or weeks)
Cell of origin - (more immature cell, blast)
Chronic leukemia: Onset - slow (months to years)
Cell of origin - (more mature cell)

Question 14

List two (2) therapeutic interventions that must be done before starting chemotherapy, to try to
prevent the development of tumour lysis syndrome.

Answer 14

a. Adequate hydration; maintain good urine output
b. Allopurinol or Rasburicase

Question 15

List four (4) biochemical features of tumour lysis syndrome.

Answer 15

. Hyperkalaemia
ii. Hyperuricaemia
iii. Hyperphosphataemia
iv. Hypocalcaemia

Question 16

List ten (10) clinical signs and symptoms that were/are/could have been present in Mr Hanlie and
that would indicate the likely presence of raised intracranial pressure.

Answer 16

-headache
-reduced conscious level
-vomiting
-localizing signs
-dilated pupil/s
-3N partial palsy
-high BP
-slow pulse
-papilloedema
-irregular breathing

Question 17

State what was the likely cause of the bifrontal contusion. Explain how it was brought about.

Answer 17

-contre-coup injury (½ mark)
-he was thrown to the ground with force, striking his occipital region against the ground. The brain [which
effectively ‘floats’ in the CSF of the cranial cavity] would have been forced against the frontal region of the
skull. These 2 surfaces abruptly collide when movement of the skull is acutely stopped when the occipital
portion of the skull ceases to move. (2 marks)

Question 18

List the lesion/s that are likely to be present in the right carotid artery in order to explain the post-
operative findings.

Answer 18

-complicated atheroma
-acute tear with superimposed thrombosis

Question 19

Briefly explain what determines the management of the left middle cerebral artery occlusion.

Answer 19

-Time of onset : if very recent onset, thrombolysis can be attempted.

Question 20

Additional blood tests were performed: Sodium 148 (135-145 mmol/L); Potassium 2.2 (3.5-5.3 mmol/L)
Urea 5 (3-6mmol/L); Creatinine 70 (60-90 umol/L)
20. State the most likely diagnosis in Jenny.

Answer 20

a. Cushing’s Syndrome (1)

Question 21

List four (4) biochemical or clinical findings in this patient that suggest this diagnosis.

Answer 21

b. Hypertension with hypokalaemia (2 x ½ = 1)
c. Clinical findings: buffalo hump, purpura, striae (any 2: 2 x ½ = 1)

Question 22

List two (2) tests that could confirm this diagnosis and state the direction of change expected.

Answer 22

Any two of the following:
i. 24 hour urine cortisol level elevated ( ½ x 2 = 1)
ii. Midnight cortisol elevated ( ½ x 2 = 1) [saliva or serum]
iii. Blunted diurnal rhythm (1)

Question 23

Briefly outline the mechanism for the hypokalaemia in this condition.

Answer 23

Excess activation of the ENaC (1) via mineralocorticoid receptor (1) in the distal tubule
causing increased Na uptake and potassium loss into the urine.

Question 24

Briefly outline the mechanism of action of aldosterone on the distal renal tubule.

Answer 24

Binds mineralocorticoid receptor (1), which increases activity of ENaC channels (1), allowing increased
uptake of Na and (therefore water) (1), with loss of potassium and hydrogen ions into the urine (1).

Question 25

Give an overview of the arterial blood supply to the cerebellum. You may use a set of well labelled diagrams as your answer.

Answer 25

Basilar, PICA, AICA, Veterbral

Question 26

Describe how two (2) forms of herniation of the brain may occur with raised intracranial pressure, using the anatomical relationships of the structures involved.

Answer 26

Uncal herniation: In uncal herniation, a common subtype of transtentorial herniation, the innermost part of the temporal lobe, the uncus, can be squeezed so much that it moves towards the tentorium and puts pressure on the brainstem, most notably the midbrain. The uncus can compress the oculomotor nerve (CN III), which may affect the parasympathetic input to the eye. Compression of the ipsilateral posterior cerebral artery will result in ischaemia of the ipsilateral primary visual cortex and contralateral visual field deficits in both eyes (contralateral homonymous hemianopsia). Central herniation: In central herniation, the diencephalon and parts of the temporal lobes of both of the cerebral hemispheres are squeezed through a notch in the tentorium cerebelli. Transtentorial herniation can occur when the brain moves either up or down across the tentorium, called ascending and descending transtentorial herniation respectively; however descending herniation is much more common. Downward herniation can stretch branches of the basilar artery (pontine arteries), causing them to tear and bleed, known as a Duret hemorrhage. The result is usually fatal. Other symptoms of this type of herniation include small, fixed pupils with paralysis of upward eye movement giving the characteristic appearance of "sunset eyes". Cingulate herniation Subfalcine herniation on CT In cingulate or subfalcine herniation, the most common type, the innermost part of the frontal lobe is forced under part of the falx cerebri, the meningeal layer of dura mater between the two cerebral hemispheres. Cingulate herniation can be caused when one hemisphere swells and pushes the cingulate gyrus under the falx cerebri. This may interfere with blood vessels in the frontal lobes that are close to the site of injury (anterior cerebral artery), or it may progress to central herniation. Transcalvarial herniation In transcalvarial herniation, the brain squeezes through a fracture or a surgical site in the skull. Also called "external herniation", this type of herniation may occur during craniectomy, surgery in which a flap of skull is removed, the protruding brain region preventing the piece of skull from being replaced during the operation. Upward herniation Increased pressure in the posterior fossa can cause the cerebellum to move up through the tentorial opening in upward, or cerebellar herniation. The midbrain is pushed through the tentorial notch. This also pushes the midbrain down. This is also known as a transtentorial herniation since it occurs across the tentorium cerebelli. Tonsillar herniation In tonsillar herniation, also called downward cerebellar herniation, transforaminal herniation, or "coning", the cerebellar tonsils move downward through the foramen magnum possibly causing compression of the lower brainstem and upper cervical spinal cord as they pass through the foramen magnum. Increased pressure on the brainstem can result in dysfunction of the centres in the brain responsible for controlling respiratory and cardiac function. The most common signs are intractable headache, head tilt, and neck stiffness due to tonsillar impaction. The level of consciousness may decrease and also give rise to flaccid paralysis. Blood pressure instability is also evident in these patients, with depression of respiratory centre.

Question 27

Briefly explain two (2) likely causes that could have led to his blindness.

Answer 27

Detached retina – separates from the RPE after blunt trauma to the head. RPE is important for extracellular ion balance around the photoreceptor cells, nourishment of photoreceptors and cycling of photopigment. Without these, electrotonic conduction of photorecpetors is not possible hence no transmission of signal to the visual cortex. (3) Intracranial bleeding and particular increased intracranial pressure that impacts on the optic nerve (sensititve to pressure) causing blindness (2)

Question 28

If Mr. Hanlie suffered damage to his brain tissue, briefly explain how survival of the neurons could be affected.

Answer 28

Immediate cell death (necrotic), as well as delayed death (apoptotic) through inflammatory processes, metabolic and respiratory stress

Question 29

State whether disrupted connections between neurons in the injured brain are likely to functionally restore themselves. Provide the reasons for your answer.

Answer 29

No, as injured CNS neurons often degenerate or fail to re-express the genes necessary for axonal regeneration. The CNS microenvironment (glia: oligodendrocytes, astrocytes and microglia) is non- permississive for axon regrowth, and molecular guidance cues are not re-expressed in the adult brain

Question 30

State under what name are the histological features of degenerating axonal pathways known.

Answer 30

Wallerian degeneration

Question 31

Name the basal ganglia structure that is damaged in patients with hemiballism.

Answer 31

subthalamic nucleus

Question 32

State whether the direct or indirect pathway is affected in hemiballism.

Answer 32

indirect pathway

Question 33

In comparison to hemiballism, name the specific brain area that accounts for the pathology (a loss of dopamine neurons) observed in Parkinson's disease

Answer 33

substantia nigra pars compacta

Question 34

There is convincing evidence that stroke leads to a large increase in the extracellular concentrations of glutamate. List the three (3) groups of receptors to which glutamate can bind.

Answer 34

Answer: NMDA, KA/AMPA and mGluRs

Question 35

Explain how both the direct and indirect pathways are modulated by a loss of dopamine input on the striatum in Parkinson's disease. State whether the overall effect is cortical excitation or inhibition.

Answer 35

Answer: Normally, to initiate movement, the effect of dopamine excites or drives the direct pathway, increasing cortical excitation - dopamine excites the direct pathway through D1 receptors and inhibits the indirect pathway through D2 receptors. However, in Parkinson’s disease, consequences for basal ganglia function are (i) decreased output from caudate/putamen to internal segment of the globus pallidus (ii) excessive tonic inhibition of ventral anterior/ventral lateral complex of the thalamus (iii) decreased activation of motor cortex via ventral anterior/ventral lateral complex, therefore an underactive cortex. People with this disease therefore have difficulty in initiating movement.

Question 36

Two weeks later Mr Hanlie had deteriorated and a repeat CT scan showed the presence of a brain abscess. 36. Outline three (3) mechanisms that may lead to the development of a brain abscess.

Answer 36

Direct head trauma Haematogenous spread from distant primary focus Eg lung abscess Spread from contiguous sites Eg otitis media/ sinusitis

Question 37

37. State which empiric antibiotics are used to treat brain abscesses and which organisms they cover.

Answer 37

Ceftriaxone – Streptococci and Staphylococci Metronidazole- Anaerobes Cloxacillin- Staphylococci

Question 38

Briefly suggest a reason why Mr Hanlie’s brother has had more bleeding problems.

Answer 38

Variable expression / environmental factors

Question 39

Outline two (2) reasons why Yolande may have low factor VIII levels.

Answer 39

Skewed X inactivation, both copies of X with mutation, X chromosome abnormality

Question 40

State what is the risk of Yolande’s baby having haemophilia A.

Answer 40

50%

Question 41

Mr Hanlie also has high blood pressure as does his father and his brother but not his two sisters. State whether you think that this could be an X- linked condition too. Explain your answer.

Answer 41

No – father to son transmission excludes X- linked inheritance

Question 42

Briefly describe what is meant by genotype/ phenotype correlation.

Answer 42

The correlation between genotype and phenotype is a statistical relationship that predicts a physical trait in a person or abnormality in a patient with a given DNA sequence or mutation.

Question 43

Name one molecular mechanism that can explain a severe phenotype.

Answer 43

Nonsense mutation creating absent / truncated protein

Question 44

List the various levels of prevention and provide an example for each for stroke.

Answer 44

PRIMORDIAL PREVENTION (0.5) National Dietary guidelines & food policies to reduce sugar and salt consumption/ E.g. Taxing sugar sweetened beverages (1) PRIMARY PREVENTION (0.5) Can mention any one of the following (1) Address NB modifiable risk factors: Dietary: reduce salt & sugar intake, increase fruit & veg intake Increase physical activity Detection & Mx of hypertension SECONDARY PREVENTION (0.5) Can mention any one of the following (1) :  Daily, low-dose aspirin/ antiplatelet agents  Carotid endarterectomy for carotid stenosis, TIA, non-disabling strokes  Diet and exercise programs to prevent further strokes  Rural villages: teach community workers to recognize stroke (FAST approach) TERTIARY PREVENTION (0.5) stroke rehabilitation programs (1)

Question 45

Briefly explain each level within the ecological framework of disease. (4 marks) Within each level, outline one example of a risk factor of violence in South Africa

Answer 45

* At the individual level, personal history and biological factors influence how individuals behave and increase their likelihood of becoming a victim or a perpetrator of violence (1). 0.5 mark for any of the following points: eg: being a victim of child maltreatment, psychological or personality disorders, alcohol and/or substance abuse and a history of behaving aggressively or having experienced abuse. * Personal relationships such as family, friends, intimate partners and peers may influence the risks of becoming a victim or perpetrator of violence (1). For example 0.5 mark for any of the points listed in the framework below * Community contexts, in which social relationships occur, such as schools, neighbourhoods and workplaces, also influence violence (1). 0.5 mark for any of the following points: Risk factors here may include the level of unemployment, poverty, crime, population density, mobility and the existence of a local drug or gun trade. * Societal factors influence whether violence is encouraged or inhibited (1). 0.5 mark for any of the following points These include economic and social policies that maintain socioeconomic inequalities between people, the availability of weapons, and social and cultural norms such as those around male dominance over women, parental dominance over children and cultural norms that endorse violence as an acceptable method to resolve conflicts.

Question 46

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