MST #1

Question 1

Pharmacokinetics is:

a.	 The study of biological and therapeutic effects of drugs

b.	 The study of absorption, distribution, metabolism and excretion of drugs

c.	 The study of mechanisms of drug action

d.	 The study of methods of new drug development

Answer 1

b.

The study of absorption, distribution, metabolism and excretion of drugs

Question 2

Pharmacodynamics can provide information about:

a.	 mechanisms of drug absorption

b.	 biological barriers

c.	 unwanted effects

d.	 excretion of a drug from the organism

Answer 2

c.

unwanted effects

Question 3

If an agonist can produce submaximal effects and has moderate efficacy it is called a

a.	 Partial agonist

b.	 Antagonist

c.	 Agonist-antagonist

d.	 Full agonist

Answer 3

a.

Partial agonist

Question 4

The pathology report of an appendix removed from a patient with a 24-hour history of abdominal pain reports numerous neutrophils in the wall.

Which of the following acts on endothelial cells to induce expression of E-selectin for the binding of neutrophils to facilitate their movement into the tissues?
	a.	
Bradykinin
	b.	
Endothelin
	c.	
Interleukin-1
	d.	
Interleukin-8

Answer 4

c. Interleukin-1

Question 5

A 15-year-old male died following a febrile illness of 24 hours duration where he had presented with photophobia, neck stiffness and a petechial skin rash. At autopsy, the meninges contained a cloudy exudate. The micrograph below is from the subarachnoid space.

The cells indicated (arrows) have predominantly migrated into this region from which type of blood vessel?

a.	 arterioles

b.	 capillaries

c.	 small arteries

d.	 veins

e.	 post-capillary venules

Answer 5

e.
post-capillary venules

The cells are neutrophils. They migrate from the blood into the tissues mostly via venules.

Question 6

Detection of troponin in the blood is used in the diagnosis of myocardial infarction (heart attack). Troponin leaks from dead cardiac muscle cells following damage to the plasma membrane. One proposed mechanism of membrane damage is that it occurs due to the action of phospholipase that is activated by

a.	 an increase in cytosolic calcium.

b.	 a decrease in cytosolic potassium.

c.	 a decrease in cytosolic hydrogen.

d.	 an increase in cytosolic sodium.

Answer 6

a.

an increase in cytosolic calcium.

Question 7

The micrograph is from an area of inflammation. Cell type K is derived from which one of the following cell types?
(Has a clockface in histology)
a.
Monocyte

b.	 Normoblast

c.	 Myeloblast

d.	 B lymphocyte

Answer 7

d.
B lymphocyte

Cell type K is a plasma cell.

Question 8

Which of the following statements about inheritance of genetic traits is correct:

a.	 A high prevalence of an autosomal recessively inherited trait in a population must be due to consanguinity.

b.	 In a pedigree showing that a particular trait is inherited in an autosomal dominant pattern, everyone who inherits the gene mutation may not show the phenotype.

c.	 First cousins once-removed share 12.5% of their genes.

d.	 In an X-linked recessive trait, affected males have a 50% chance of passing on the mutated gene to their sons.

Answer 8

b. In a pedigree showing that a particular trait is inherited in an autosomal dominant pattern, everyone who inherits the gene mutation may not show the phenotype.

Although a high prevalence of an autosomal recessively inherited trait in a population may be due to consanguinity, it may also be due to founder effects, which is the loss of genetic variation when a particular population is is established from a small number of people who have that mutation. It may also be due to heterozygote advantage, in which being a carrier (heterozygote) confers some advantage over homozygous states, so that there is more chance that the heterozyguous individual passes on this allele to their offspring (ie higher degree of fitness), such as in the case of sickle cell carriers who have partial resistance to malaria.

First cousins once removed are 4th degree relatives and share 6.25% of their genes.

Males only pass on their X chromosomes to daughters not sons, so in an X-linked recessive trait, affected males do not have affected sons.

Question 9

Which one of the following statements regarding the muscles of the back is correct?
a.
The erector spinae muscles act primarily as segmental stabilisers.
b.
The erector spinae muscles have a common origin which includes the iliac crest, sacrospinous ligament and lumbar vertebrae.
c.
The middle layer of lumbar (thoracolumbar) fascia receives attachments of all anterior abdominal wall muscles.
d.
The erector spinae muscles are innervated by anterior rami of segmental spinal nerves.

Answer 9

b. The erector spinae muscles have a common origin which includes the iliac crest, sacrospinous ligament and lumbar vertebrae.

Erector spinae are primary extensors of the spine, innervated by posterior rami of the segmental spinal nerves. The posterior layer ( not the middle layer) of thoracolumbar fascia receives attachment from some of the anterior abdominal wall muscles . So only B is correct.

Question 10

Which one of the following statements in relation to the back is CORRECT?
a.
A lordotic curve is a primary curve found in the thoracic spine.
b.
Facets on typical lumbar articular surfaces are oriented in the coronal plane and limit flexion and extension.
c.
A herniated disc involves the nucleus pulposus projecting through the annulus fibrosus.

d.	 The posterior longitudinal ligament passes along the spinous processes of all thoracic and lumbar vertebrae.

Answer 10

c. A herniated disc involves the nucleus pulposus projecting through the annulus fibrosus.

Question 11

Which one of the following statements regarding the the physiological effects of caffeine is INCORRECT?

a.	  It opposes the effect of adenosine on adenosine receptors.

b.	 It increases cyclic AMP levels in pacemaker cells.

c.	 It increases contractility of cardiac muscle.

d.	 It stimulates the heart rate.

Answer 11

c.

It increases contractility of cardiac muscle.

Question 12

What is a disability-adjusted life year (DALY)?
a.
A measure of illness expressed as the number of years lost due to disability.
b.
A measure of how long people will live with disability.
c.
A measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death.
d.
A measure of quality of life used by aged care and disability planners

Answer 12

c. A measure of overall disease burden, expressed as the number of years lost due to ill-health, disability or early death.

DALYs for a disease or health condition are calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the Years Lost due to Disability (YLD) for incident cases of the health condition:

Calculation DALY = YLL + YLD

One DALY can be thought of as one lost year of “healthy” life. The sum of these DALYs across the population, or the burden of disease, can be thought of as a measurement of the gap between current health status and an ideal health situation where the entire population lives to an advanced age, free of disease and disability.

Question 13

The structure of which part of an antibody defines its isotype?

a.	 the J chain

b.	 the variable regions of the light chains

c.	 the variable regions of the heavy chains

d.	 the constant regions of the heavy chain

Answer 13

d.
the constant regions of the heavy chain

sotypes are defined by the sequence, and therefore structure of the heavy chain. For example the gamma heavy chain will give rise to an IgG antibody, while an alpha heavy chain will give rise to an IgA molecule. What are the recombination events that take place to give rise to a change of isotype?

Question 14

Which of the following statements is INCORRECT?

a.	 An IgG expressing B cell can isotype switch to IgA

b.	 IL-4 signalling promotes Isotype switching to IgE

c.	 An IgA expressing B cell can isotype switch to IgG

d.	 Isotype switching is catalysed by activation induced cytodine deaminase (AID)

Answer 14

c.
An IgA expressing B cell can isotype switch to IgG

Isotype switching involves a DNA recombination event, catalysed by activation induced cytidine deaminase (AID), that results in an assembled V-region (VDJ) region being spliced onto a new heavy chain constant domain. The constant domain gene segments are down stream of the recombined VDJ gene sequence with the germ-line gene order being Cμ, (encoding IgM) Cδ (encoding IgD), Cγ (IgG), Cε (IgE) and Cα (IgA). Isotype switching occurs via non-homologous DNA sequences (termed switch regions) that lie in between Cμ, Cγ, Cε and Cα. Note that there is no switch region between Cμ and Cδ gene segments. When a B cell isotype switches from IgM/IgD expression to a new isotype, there is deletion of the intervening DNA sequence. For example, if a B cell isotype switches to IgA (the last constant gene segment in the heavy chain locus), it cannot then revert back to IgG as the Cγ genomic sequence has been deleted. In constrast, an IgG expressing B cell can further isotype switch to IgE or IgA. Cytokine signalling is key for promoting/skewing isotype switching towards a particular isotype (eg IFN-γ promotes IgG, IL-4 promotes IgE and TGFβ promotes IgA).

Question 15

Activation of dendritic cells in the tissues upon infection results in which of the following events?

a.	 Increased pinocytosis and sampling of antigen

b.	 Upregulation of CD40L and production of cytokines

c.	 Down-regulation of CD80/CD86

	d.	
Upregulation of MHC class I and class II molecules

Answer 15

d. 
Upregulation of MHC class I and class II molecules

Activation of DCs in the tissues can occur after binding of Pattern recognition receptors with pathogen components (eg LPS binds to TLR4). This results in decreased pinocytosis (sampling of antigens from the microenvironment), increased expression of processing machinery, increased MHC expression. Activated DCs down regulate the anchor molecules holding them in the tissues and with upregulation of chemokine receptors (particularly CCR7), they are now able to migrate to the draining lymph node. They also upregulate costimulatory molecules (CD80/CD86) and can produce cytokines (eg IL-12) required for full activation of naïve T cells in the lymph node. Note that activated CD4+ T cells will express CD40L that can interact with CD40 on DCs. This licensing of DCs via CD40 ligation helps promote better activation of CD8+ T cells.

Question 16

Which of the following statements is INCORRECT?
a.
IL-12 and IFN-ϒ production can drive TH1 CD4 T cell differentiation.
b.
IL4 can drive TH2 CD4 T cell differentiation.
c.
IL-6 signalling contributes to TH17 and Treg cells.
d.
TGFβ signalling contributes to generation of Treg cells.

Answer 16

c. IL-6 signalling contributes to TH17 and Treg cells.

IL-6 can act as signal 3 upon T cell activation and helps drive naïve CD4 T cell differentaiton towards both the TH17 pathway (together with IL21) and T follicular helper cells (TFH). Th17 cells produce IL-17, important in pro-inflammatory responses, recruitment of neutrophils from the circulation and protection from extracellular pathogens. TFH cells produce IL-6 and IL-21, are found in the germinal centre structures in the B cells area of the lymph node and are key for helping sustain germinal centre reactions where activated B cells undergo isotype switching and affinity maturation.

Question 17

Which of the following statements rearding MHC polymorphism/s is CORRECT?

	a.	
It is found predominantly in all domains of the MHC class I molecule.

b.	 They are found predominantly where the CD4 or CD8 co-receptors interact

c.	 They can influence the spectrum of peptides that bind to a particular MHC molecule

d.	 They can directly impact the ability to activate NK T cells

Answer 17

c.
They can influence the spectrum of peptides that bind to a particular MHC molecule

The majority of MHC polymorphisms (i.e sequence variation between individual genes) is focussed within the peptide binding groove, particular in the pockets within the floor of the groove that accomodate peptide side chains. Changes in these pockets alters peptide binding specificity, and hence peptides with different amino-acid motifs will bind. In this way, the immune system has evolved a mechanism to ensure a greater array of antigenic-peptides can be presented from a pathogen. Of course, some of these polymorphisms can be found in residues within MHC -helices that may interact with TCR. Hence polymorphisms in these regions will alter T cell recognition. Remember, NK cells co-express both activating and inhibitory receptors with the latter being able to recognise classical MHC class I molecules. Upon infection, some pathogens down-regulate MHC class I removing the capacity for inhibition of NK cells. Upon interaction with an infected cell, NK cells will be activated and kill the cell using similar mechanisms to CD8+ killer T cells (delivery of cytotoxic molecules).

Question 18

Which of the following antibody molecules is most efficient at triggering the classical complement cascade?
	a.	
IgA
	b.	
IgD
	c.	
IgG
	d.	
IgE

Answer 18

c. IgG

Remember that IgM and IgG (esp IgG1 and IgG3) are the most efficient at fixing complement. They are also excellent at opsonisation. IgA is useful in neutralization. It is found in mucosa and mucosal secretions. IgE is most often associated with mast cells. IgE binds to mast cells via cell surface Fce-receptors. Crosslinking of IgE molecules on mast cell surfaces induces degranulation. IgD is expressed on naïve B cells. Upon activation IgD is rapidly downregulated and not re-expressed. It is not clear what the role of IgD in the immune system is

Question 19

Which of the following components of the complement cascade form the C5 convertase?
	a.	
C4bC2bC3b
	b.	
C3aFactorB
	c.	
C3bC5bC6
	d.	
C5bC6C7C8

Answer 19

a. C4bC2bC3b

The C4bC2b3b protein complex is an enzymic complex that cleaves C5 and intitiates formation of the membrane attack complex (MAC). Initiation of complement activation via the classical pathway involves antibody (IgM, IgG1/IgG3) binding of C1q to the Ab-Ag complex. This in turn recruits the C1r and C1s components that are able to cleave C2 and C4 components (forming C2a, C2b, C4a and C4b breakdown products). C2b and C4b associate to form a C3 convertase cleaving C3 into C3a and C3b. C3b then associates with C4bC2b to form the C5 convertase.

A note regarding information in text books. Some text books report that it is C2a, not C2b that forms part of the C5 convertase. This confusion is a consequence of inapprorpriate usage of nomenclature in the scientific literature. In this case, conflicting assignment of both C2a and C2b was used to describe the larger fragment generated after cleavage. The current convention is to assign the designation (b) to the larger fragment generated after cleavage. Hence, the correct nomenclature is C2b as it is the larger fragment that forms part of the C3 and C5 convertase protein complex. The appropriate text book is Janeways Immunolobiology (7th edition).

Question 20

Which of the following features distinguishes bacterial cells from eukaryotic cells?

a.	 The presence of a wall in bacterial cells.

b.	 The presence of flagella on bacterial cells.

c.	 The absence of membrane-bound organelles from the cytoplasm of bacterial cells.

d.	 The presence of 18S RNA in the ribosomes of bacterial cells.

Answer 20

c.
The absence of membrane-bound organelles from the cytoplasm of bacterial cells.

of the four options, the best answer is c. Eukaryotic cells can have a wall and/or flagella. All eukaryotic cells have 18S rRNA and membrane-bound organelles.

Question 21

Which of the following is NOT a property of the members of the genus Clostridium?
	a.	
Gram-positive cell wall.
	b.	
The ability to produce spores.
	c.	
The need to grow in the absence of oxygen.
	d.	
The ability to cause anthrax.

Answer 21

d. The ability to cause anthrax

Anthrax is caused by Bacillus anthracis, a Gram-positive AEROBIC spore-forming bacillus.

Question 22

Which of the following is a common property of bacterial endotoxins and exotoxins?

a.	 Both are released from bacteria and can act at sites remote from the site of infection.

b.	 Both typically act by binding to pattern recognition receptors on immune cells.

c.	 Both are highly antigenic and are neutralised by antibodies against them.

d.	 Both can be converted into immunogenic toxoids.

Answer 22

a.
Both are released from bacteria and can act at sites remote from the site of infection.

Bacterial exotoxins are proteins that are secreted from bacteria, and bind to specific receptors on target cells that may be quite distant from the site of infection. Being proteins, they are highly immunogenic, and can be inactivated so that they retain they immunogenicity but loose their pathogenicity (toxoids). Endotoxins are lipopolysaccharides or lipo-oligosaccharides that are released from the surface of Gram-negative bacteria when they die, but also by a process of membrane shedding and that bind certain pattern-recognition receptors (TLR-4). Being lipopolysaccharides, they are much less antigenic than endotoxins, but are much more stable (for example, they require temperatures of 240oC for 4 hours for their inactivation). In general, endotoxins are not neutralised by antibodies which bind to them, and can not be converted into toxoids.

Question 23

The bacterial genome may include:

a.	 paired linear chromosomes.

b.	 a closed loop of supercoiled single-stranded DNA.

c.	 double-stranded DNA containing introns and exons.

d.	 one or more independently replicating plasmids.

Answer 23

d.
one or more independently replicating plasmids.

The bacterial genome comprises a signle circular chromosome, comprising double-stranded DNA, and may include one or more independently replicating plasmids.

Question 24

You have set up a solid phase assay to detect the presence of IgM antibodies to rubella virus in the serum of a pregnant woman. Which of the reagents listed below was the first reagent you attached to the wells of a micro-titre tray, if the second reagent was the patient’s serum, the third reagent was rubella antigen, the fourth reagent was enzyme labelled anti-rubella immunoglobulin, and the final reagent was the enzyme’s substrate?

a.	 Anti-rubella IgG

b.	 Anti-human IgG

c.	 Anti-human antibodies

d.	 Anti-human IgM

Answer 24

d.
Anti-human IgM

If we wish to detect the presence of IgM antibodies to rubella virus using the format describe above, we would need to capture antibodies of the IgM isotype from the patient’s serum, by using anti-human IgM to coat the wells of the microtitre tray.

Question 25

Which one of the following is INCORRECT?

a.	 Health promotion is the process of enabling people to increase control over, and to improve their health.

b.	 Primary prevention prevents or minimises the progress of a disease .

c.	 Public Health is the science and art of preventing disease, prolonging life and promoting, protecting and improving health through the organised efforts of society.

d.	 Primary Health care is universally accessible, scientifically sound first level care provided by a suitably trained workforce.

Answer 25

b.
Primary prevention prevents or minimises the progress of a disease .

Primary prevention reduces the likelihood of the development of a disease.
Secondary prevention prevents or minimises the progress of a disease.

Question 26

All of the following statements relating to a healthy cell’s resting membrane potential are correct except for:
a.
The resting membrane potential is mostly due to potassium.
b.
The concentration difference of an ion across a membrane is the only important factor in determining the contribution of that ion to the resting membrane potential.
c.
Cl- is usually in electrochemical equilibrium because it follows the resting membrane potential.
d.
For a given ion, the concentration and electrical gradients may be in the same direction across the membrane.
e.
For a given ion, the concentration and electrical gradients may be in opposite directions across the membrane.

Answer 26

b. The concentration difference of an ion across a membrane is the only important factor in determining the contribution of that ion to the resting membrane potential.

Question 27

A decrease in left ventricular (LV) compliance will lead to which of the following?
	a.	
a decrease in LV contractility
	b.	
an increase in LV contractility
	c.	
an increase in end-diastolic volume
	d.	
a decrease in end-diastolic pressure
	e.	
a decrease in stroke volume

Answer 27

e. a decrease in stroke volume

Question 28

Which one of the following statements about haemopoiesis is correct?

a.	 Red blood cells (erythrocytes) are made in the red bone marrow and white blood cells (leukocytes) are made in the yellow bone marrow.

b.	 There is a functional reserve pool of immature neutrophils which is equivalent to about 5 days of neutrophil production.

c.	 Red and white blood cells and megakaryocytes are derived from different pluripotential progenitor cells.

d.	 Platelets are formed by the break-up of granulocytes in the bone marrow.

Answer 28

b.
There is a functional reserve pool of immature neutrophils which is equivalent to about 5 days of neutrophil production.

All blood cells are derived from a single pluripotential progenitor cell (CFC). Both red and white blood cells are formed in red bone marrow. Yellow bone marrow is adipose tissue. Platelets are derived from megakaryocytes. See lecture content and Wheater’s Functional Histology.

Question 29

Which one of the following statements about epithelia is correct?

a.	 Junctions that permit the passage of small molecules for intercellular signalling are uncommon in epithelia.

b.	 Normal surface epithelia are always associated with a basement membrane.

c.	 Cell death and replacement in surface epithelia is usually very slow (over years).

d.	 Surface epithelia contain many capillaries to support their high metabolic rate.

Answer 29

b.
Normal surface epithelia are always associated with a basement membrane.

A basement membrane is associated with the basal layer of every epithelium. Direct cell-to-cell contact and linkage of cells by a variety of intercellular junctions is the rule. Stem cells of surface epithelia are continuously dividing to replace those lost. Blood vessels are not present in epithelia - they are in the connective tissue on the other side of the basement membrane.

Question 30

Which of the following statements about chemical fixation and paraffin embedding of tissue is correct?

a. Formalin cross links proteins (among other molecules) to preserve tissue structure.
b. Addition of a separate substance in addition to formalin to prevent putrefaction is required.
c. Molten paraffin wax is miscible with formalin.
d. Formalin weakens the tissue and embedding in paraffin wax is required to make sectioning possible.

Answer 30

Formalin cross links proteins (among other molecules) to preserve tissue structure.

Formaldehyde is a reactive molecule that can readily cross-link the amino acids of proteins, primarily the amino acid lysine. Formaldehyde is a powerful antibacterial. Molten wax is not miscible with formalin. Formalin fixed tissue needs to have the water removed before embedding in paraffin. Fixation toughens tissue, not weakens it.

Question 31

These are all high power images of leukocytes in a blood smear. Which image (A-D) demonstrates a cell that is involved in allergic reactions and inflammatory responses to parasites and is likely to be present in elevated numbers in the blood of such patients?

a.	 A

b.	 B

c.	 C

d.	 D

Answer 31

c.

C eosinophil.

Question 32

The following micrograph is of infarcted myocardium.
Which one of the following processes is likely to have occurred in these cells and contributed to the development of this abnormality?

a.	 activation of caspases

b.	 increase in superoxide dismutase

c.	 decrease in hydrogen peroxide

d.	 increase in cytosolic calcium

Answer 32

d.
increase in cytosolic calcium

The micrograph is a high power view of infarcted muscle cells. They can be seen to be necrotic as they have lost their nuclei. These cells have undergone ischaemic necrosis, during which calcium pumps, dependent on ATP, will not be able to function adequately so calcium accumulates in the cytoplasm. Activation of caspases occurs in apoptosis. Hydrogen peroxide (a reactive oxygen species) would be expected to increase, contributing to damage. Superoxide dismutase protects against the accumulation of reactive oxygen species.

Question 33

The following micrograph is from the edge of an abnormal area of myocardium found at autopsy on a 68-year-old man with a long history of ischaemic heart disease. The pathologist reports that he has had a myocardial infarct.

What pathological process does the micrograph demonstrate?

a.	 acute inflammation

b.	 coagulative necrosis

c.	 chronic inflammation

d.	 organization

Answer 33

d.
organization

The micrograph shows granulation tissue which forms during healing. The process of healing by granulation tissue is called organization. The muscle cells at the edge of the micrograph are still viable (their nuclei are normal) i.e. no coagulative necrosis is seen.

Question 34

A 42-year-old woman presents with general malaise. She is found to have a mild fever, anaemia and an elevated serum C reactive protein level. Assuming that these features are related, which one of the following is the most appropriate interpretation of the patient’s underlying condition? The patient has

a.	 an acute infective process

b.	 a chronic infective process

c.	 an acute inflammatory process

d.	 a chronic inflammatory process

Answer 34

d.
a chronic inflammatory process

Malaise, fever and elevated C reactive protein may occur with both acute and chronic inflammatory processes. Inflammatory processes are not always due to infection and there is nothing here to suggest that her condition is infective in nature. Anaemia can develop in association with inflammation (in response to hepcidin release from the liver) but it develops over time i.e. it occurs in association with chronic inflammation (anaemia of chronic disease).