MODEL ANSWERS PHSL2004 TEST 1

APQ 1

The following table shows data from four patients (A, B, C and D) who each weight 70kg
and have body fluid balance abnormalities.

Patient Normal
A B C D Values
Plasma osmolarity (mmol/l) 285 296 301 272 280 – 295
Extracellular fluid volume (l) 13 13 15 15 14
Intracellular fluid volume (l) 28 27 27 29 28

1. Giving a physiological explanation for the data shown in each case, identify which
patient (A, B, C or D) best represents a person:

a) who is sweating profusely without fluid replacement.

B. Sweating is hypotonic fluid loss (½).

® ¯ ECF volume and plasma osmolarity will become hypertonic (1). Water
will move from ICF to ECF to equalize ECF osmolarity ¯ ICF (½ ).
(2)

b) with increased aldosterone secretion (Conn’s syndrome).

C. Conn’s syndrome is a salt gain (½).

® plasma osmolarity will become hypertonic (1). Water will move from ICF
to ECF to equilibrate ECF osmolarity. ECF and ¯ ICF volumes (1).
(2)

c) with acute haemorrhage.

A. loss of isotonic solution from ECF (½).

® no change in plasma osmolarity (½) but ¯ ECF volume (½). The ICF
volume is unchanged (½).
(2)

d) with increased antidiuretic hormone (ADH or vasopressin) secretion.

D. Hypotonic fluid gain (½).

® ECF volume and plasma osmolarity will become hypotonic (1). Water
will move from ECF to ICF to equilibrate ECF osmolarity ICF (½).
(2)

2. Citing evidence from the table to support your answer, identify the patient (A, B, C or
D) that is most likely to have an increased blood pressure.

Patient C and D because they have an increased ECF volume (2).

(2)
APQ 2

The table below show metabolically important enzymes, their co-enzymes, the groups that
are transferred by the co-enzymes, the vitamins from which the co-enzymes are derived and
consequences of vitamin deficiencies. Complete the table following the example provided for
lactate dehydrogenase.

Enzyme Lactate Succinate Thymidilate Fatty acid

dehydrogenase dehydrogenase/ synthase synthase
Complex II
Reaction Lactate « Succinate ® dUMP ® dTMP Malonyl-CoA
catalysed pyruvate fumarate (deoxyuridine + acetyl-CoA
monophosphate ® ® fatty acid
deoxythymidine
monophosphaste)
Metabolic Glycolysis Tricarboxylic acid Synthesis of Fatty acid
pathway cycle (TCA ) OR nucleotides OR synthesis OR
Krebs cycle OR synthesis of DNA lipid
electron transport OR pyrimidine anabolism
chain (ETC) OR synthesis
oxidative
phosphorylation
Co-enzyme NAD+ FAD N5, N10-methylene NADPH
tetrahydrofolate
Group H- (hydride ion) 2 H (hydrogen CH3 (methyl H- (hydride
transferred atoms) OR electrons groups) ion) OR
by co- electrons
enzyme Accept
hydrogen
atom NOT H+
Vitamin Niacin (B3) Riboflavin (B2) Folic acid Niacin (B3)
Accept B12
Disease, Dermatitis, Angular stomatitis, Megaloblastic Dermatitis
sign or pellagra, dermatitis anaemia OR spina OR pellagra
symptom dementia bifida OR OR dementia
of vitamin macrocytic
deficiency anaemia
[10]
APQ 3

The table below shows laboratory results for samples collected from three individuals (A, B,
and C) each with a different metabolic condition.

= higher than in a normal subject; ¯ = lower than in a normal subject; N = similar to a

normal, well-fed subject; - = not measured.
Individual
Laboratory result A B C
Blood glucose concentration N -
Plasma insulin concentration - ¯ -
Plasma free fatty acid concentration -
Urine ketone concentration -
Plasma ammonia concentration - -
Plasma urea concentration ¯

1. Explaining the biological mechanisms for each of the underlined data in the table,
decide which individual (A, B, or C) is most likely to:

a) have untreated diabetes mellitus.

B. Lack of insulin leads to decreased absorption of glucose (for glycolysis and

glycogen synthesis) resulting in increased glucose in the blood. (1).
OR
In the absence of insulin (low insulin:glucagon ratio), glucagon stimulates
gluconeogenesis and glycogenolysis) resulting in increased glucose in the
blood. (1)

In the absence of insulin, hormone sensitive lipase (HSL) is not inhibited (OR
glucagon release is not inhibited and it stimulates HSL (1). HSL catalyses
lipolysis of triacylgylcerol (TAG) leading to release of free fatty acids into the
blood (1), leading to increased free fatty acids in the plasma.
Increased free fatty acids leads to increased b-oxidation of free fatty acids. b-
oxidation of fatty acids leads to accumulation of acetyl-CoA (1) (due to
depletion of NAD+ and oxaloacetate, which are needed for the TCA cycle to
metabolize acetyl-CoA). Accumulation of acetyl-CoA leads to ketogenesis (1)
and excretion of ketones in the urine, hence increased ketones in the urine.
Low cellular glucose levels lead to catabolism of proteins and amino acids for
gluconeogenesis, leading to increased metabolism of amino groups to urea,
hence increased plasma urea concentrations (1).

(any 4)
b) be a healthy person who has not eaten for more than 12 hours.

A. A healthy person who has not eaten will have normal blood glucose,
because glucagon stimulates glycogenolysis and gluconeogenesis (1).
Glucagon stimulates HSL which stimulates lipolysis leading to increased free
fatty acids in the plasma (1).
Increased free fatty acids leads to increased b-oxidation of free fatty acids. b-
oxidation leads to accumulation of acetyl-CoA (1) (due to depletion of NAD +
and oxaloacetate, which are needed for the TCA cycle to metabolize acetyl-
CoA). Accumulation of acetyl-CoA leads to ketogenesis (1) and excretion of
ketones in the urine, hence increased ketones in the urine.
Glucagon stimulates gluconeogenesis from amino acids. Metabolism of amino
acids leads to increased metabolism of amino groups to urea (1), resulting in
increased concentrations of urea in the plasma.
(any 4)
c) have liver failure.

C. In liver failure, the liver is unable to metabolise ammonia (which results

from metabolism of amino acids) leading to increased ammonia in the
plasma (1). Poor metabolism of ammonia to urea due to lack of the urea cycle
leads to low concentrations of urea in the plasma (1).
(2)

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APQ 4

The data sets below show basal oxygen consumption and plasma lactate concentrations in
three patients (A, B and C).

Normal A B C
Basal oxygen consumption (ml/min) 200-250 220 360 150
Plasma lactate (mmol/l) 1.1-2.3 1.5 8.0 8.0

1. Explaining the physiological mechanisms underlying your choice, decide which data
set (A, B or C) best fits a patient who has:

a) a deficiency of an enzyme in the electron transport chain (ETC).

C. Decreased activity of an enzyme in the ETC would decrease the reduction

of O2 to H2O, thus decreasing O2 consumption. The decreased activity of the
ETC would result in decreased proton pumping and hence a decreased proton
gradient across the inner mitochondrial membrane. The decreased proton
gradient would result in decreased activity of the F0F1 ATP synthase
resulting in less ATP synthesis. The decreased ATP leads to increased
concentrations of AMP, which activate glycolysis (phosphofructokinase 1).
Increased glycolysis leads to build up of pyruvate, which is converted to
lactate, causing high plasma lactate.
OR
Decreased conversion of NADH to NAD+ by the ETC leads to decreased
NAD+, which is needed for the TCA cycle. Decreased activity of the TCA cycle
leads to accumulation of acetyl-CoA. Acetyl-CoA inhibits pyruvate
dehydrogenase (PDH, which converts pyruvate to acetyl-CoA). Therefore
pyruvate accumulates and is converted to lactate, causing increased plasma
lactate.
(2)
b) uncoupled oxidative phosphorylation.

B. Uncoupled oxidative phosphorylation allows protons to “leak” across the

inner mitochondrial membrane, decreasing the proton gradient. The
decreased proton gradient decreases synthesis of ATP (1/2), leading to
increased concentrations of ADP. ADP activates TCA cycle enzymes
(isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase) and
increasing production of the ETC substrates NADH and FADH 2. Increased
ETC substrates increase the activity of the ETC, leading to increased
conversion of O2 to H2O, thus increasing oxygen consumption. The decreased
ATP synthesis also leads to increased AMP which increases glycolysis leading
to increased lactate.
(2)
c) cyanide poisoning.

C. Cyanide inhibits the ETC by blocking binding of O2 to complex IV. This

inhibits reduction of O2 to H2O, decreasing O2 consumption. It also causes a
build-up of reduced intermediates of the ETC and thus inhibits pumping of
protons across the inner mitochondrial membrane, leading to a decreased
 proton gradient. The decreased proton gradient leads to decreased synthesis
of ATP and increased AMP, which activates glycolysis and accumulation of
lactate.
OR
Decreased conversion of NADH to NAD+ by the ETC leads to decreased
NAD+, which is needed for the TCA cycle. Decreased activity of the TCA cycle
leads to accumulation of acetyl-CoA. Acetyl-CoA inhibits pyruvate
dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Therefore
pyruvate accumulates and is converted to lactate, causing increased plasma
lactate.

(2)

2. Patient C has a decreased plasma glucose concentration. Citing evidence from the
data set, briefly explain the physiological mechanisms leading to the reduced plasma
glucose concentration in this patient.

Decreased ATP production in the ETC increases AMP and increases generation of
ATP by anaerobic glycolysis which consumes more glucose and so reduces plasma
glucose concentration. Evidence of increased glycolysis is the increased lactate.
(2)

3. Which one of patients A, B, or C will have an increased core body temperature?

Briefly explain.

B. Increased activity of the ETC, which is shown by increased oxygen consumption,

leads to increased proton pumping. The protons are not used to synthesize ATP,
which is shown by increased lactate, so the energy is released as heat.
(2)

[10]