Formative Questions

Question 0

A 19-year-old student is concerned that he had gained so much weight since coming to University that his clothes no longer fit.
He takes very little exercise preferring to relax in the Hall Bar.
You examine him and take a simple dietary history: Your findings are:
Daily energy intake ~ 15,000 kJ Daily intake of carbohydrate ~300g
Daily intake of fat ~ 200g Daily intake of protein ~20g
Daily servings of fruit and vegetables ~2
Units of alcohol consumed per week = 35 (recommended limit 21)
Height = 1.68 m, weight = 90 Kg

Calculate the patient’s Body Mass Index (BMI). What do you conclude
from the value of the patient’s BMI?

Give TWO reasons why the patient has gained so much weight.

The energy content of the carbohydrate and fat the patient consumes
each day is less than his total daily energy intake. What is the most likely source of the extra energy?

List five aspects of the patient’s diet that give you cause for concern.

If this young man decided to go on a crash diet involving an extended
period of fasting what would be the order in which potential fuel
molecules would be mobilised and utilised?

Answer 0

BMI = 31.9 Kg/m2
He is obese or clinically obese (no mark for overweight)

Daily energy intake exceeds energy requirement (energy
requirement sedentary male

Question 1

Paracetamol is safe at normal doses. However, briefly explain how an overdose can cause damage to the liver

Answer 1

With high levels of paracetamol, the normal phase II pathway is saturated.
Metabolism switches to phase I pathway, which produces a toxic product: NAPQI. Toxic to hepatocytes.
NAPQI undergoes phase II conjugation with glutathione, so depleting hepatocytes of this anti-oxidant defence

Question 2

Define homeostasis

Answer 2

The control of the internal environment within set limits:

a dynamic equilibrium

Question 3

Define the term basal metabolic rate

List some factors that may affect it

Answer 3

The energy required to maintain life
(I.e. For functioning of various tissues of the body at physical, digestive & emotional rest)

Body weight, body temp, gender, thyroid status, pregnancy/lactation

Question 4

Briefly explain how uncoupling proteins (UCPs) are involved in heat generation in the body

Answer 4

UCPs allow a leak of proteins across the membrane, reducing the p.m.f.
The energy is dissipated as heat rater than ATP production.
UCP1 is expressed in brown adipose tissue & is involved in thermogenesis

Question 5

Define anabolism & catabolism

Answer 5

Anabolism:
The building up of larger molecules from smaller ones, requiring energy (reductive)

Catabolism:
The breakdown of larger molecules into smaller ones, releasing energy (oxidative)

Question 6

List some metabolic pathways that can be described ad anabolic & some that can be described as catabolic

Answer 6

Anabolic:
Gluconeogenesis, glycogenesis, fatty acid synthesis, ketogenesis, cholesterol synthesis

Catabolic:
Glycolysis, pentose phosphate pathway, glycogenolysis, lipolysis, fatty acid oxidation

Question 7

Give examples of high energy signals.

Explain why catabolism is generally activated by low-energy signals

Answer 7

ATP, NADH, NADPH, FAD2H

Low energy signals indicate the cell has inadequate energy levels if its immediate needs
So catabolism needs to occur to release energy from fuel molecules

Question 8

State the catabolic & anabolic roles of the TCA Cycle

Answer 8

Catabolic:
C atoms (CH3CO-) oxidised to CO2
NAD+ -> NADH
FAD -> FAD2H
GDP -> GTP

anabolic:
Provides precursors for:
Amino acids, haem, fatty acids, glucose

Question 9

Why are there no known genetic defects causing a complete deletion of an enzyme involved in the TCA cycle?

Answer 9

Crucial cycle, particularly with catabolism

Any genetic defect causing an enzyme deletion would be lethal

Question 10

Explain where, how & why lactate is produced

Answer 10

Where:
Tissues carrying out anaerobic glycolysis
Exercising skeletal muscle, rbc, wbc, kidney medulla

How:
Lactate dehydrogenase converts pyruvate to lactate

Why:
To enable NADH to be oxidised back to NAD+ so that glycolysis (when NAD+ -> NADH) can continue
Therefore some energy produced for tissues without mitochondria/O2

Question 11

Once formed, how is lactate subsequently used by the body?

Answer 11

Circulated in the blood
Taken up by heart muscle & liver (& kidney)

Lactate -> pyruvate (by LDH)
Pyruvate -> catabolism (heart muscle)
Pyruvate -> gluconeogenesis (liver & kidney)

Question 12

A patient with heart disease complains of intense muscle cramps following vigorous exercise. You discover he has elevated levels of lactate in his blood.

Why is the patient particularly prone to muscle cramps during exercise?

Answer 12

Heart condition = impaired blood & therefore oxygen supply to tissues (poor perfusion)

Therefore increased anaerobic metabolism, especially in skeletal muscle during exercise, which causes increased lactate production

Diseased heart may be unable to use lactate & may be a lactate producer

Question 13

Name some molecules that can cause metabolic acidosis & explain why

Answer 13

Ketone bodies, pyruvate, lactate, fatty acids, amino acids

All contain acidic groups

Question 14

State two tissues in which glycogen is stored

State what these stores are used for in each tissue

Answer 14

Liver
Used to maintain blood glucose at 4-5mM

Skeletal muscle
Used to provide glucose 6 phosphate to be catabolised (via glycolysis) to produce energy

Question 15

How is glycogen storage regulated

Answer 15

Glycogen synthesis controlled by regulation of glycogen synthase (insulin activates)

Glycogen degradation controlled by regulation of glycogen phosphorylase (glucagon or adrenaline activate)

Question 16

What is the major energy storage molecule in mammals?

Why is this a more efficient energy store than glycogen?

Answer 16

Triacylglycerol

Hydrophobic, so not associated with lots of H2O (i.e. Denser)

More reduced, so yields more energy when oxidised

Question 17

How is the TAG molecules used to provide the body with energy

Answer 17

Hydrolysed in adipose tissue to fatty acids & glycerol
Mobilised in response to low glucose

Fatty acids (transported bound to albumin) to consumer tissues, where oxidised to produce energy

Glycerol can also be phosphorylated & fed into glycolysis (at C3 stage) to produce energy

Question 18

Briefly outline the process of oxidative phosphorylation

Answer 18

Reduced co enzymes are re-oxidised

Electron passed along electron transport chain to O2, releasing energy

Energy drives H+ transport across membrane

H+ gradient produced

H+ re-enters via ATP synthase (ATP synthesis)

Question 19

What are the 2 main functions of oxidative phosphorylation

Answer 19

Oxidise NADH/FAD2H

Synthesise ATP

Question 20

Explain the effect dinitrophenol (DNP) has on oxidative phosphorylation

Answer 20

Increases permeability of mitochondria, membrane to H+ ions

So uncouples electron transport from ATP synthesis

Question 21

Explain why the effect of an inhibitor of a key enzyme in the ETC (e.g. Cyanide) is different to that of dinitrophenol

Answer 21

Enzyme inhibitor disrupts ETC (blocks passage of electron to O2)
So that energy is not available to drive pumping of protons to produce p.m.f.
Without p.m.f. ATP not produced and heat is not produced

Uncouplers increase permeability of inner mitochondrial membrane to proteins
collapses the proton gradient (p.m.f.)
ATP not produced, but potential energy of the p.m.f. Is dissipated as heat

Question 22

What are the 5 differences between oxidative phosphorylation & substrate level phosphorylation

Answer 22

OP:
Requires membrane assoc complexes (inner mitochondrial membrane)
Energy coupling occurs indirectly thru generation/utilisation of a proton gradient (p.m.f.)
Cant occur in absence of oxygen
Major process for ATP synth in calls requiring large amts of energy
Mitochondrial

SLP:
Requires soluble enzymes (cytoplasmic & mitochondrial matrix)
Energy coupling occurs directly thru formation of high energy of hydrolysis bond (phosphoryl grp transfer)
Can occur to limited extent in absence of oxygen
Minor process for ATP synthesis in cells requiring large amts of energy
Cytoplasmic

Question 23

A 25 year old man with type 1 diabetes mellitus has polyuria and polydipsia.
He has a blood glucose of 42 mmol/L (reference range 3.3 – 6.0), +++
positive ketonuria and a blood pH of 7.1 (reference range 7.38–7.46).
Which is the main metabolic disturbance in this situation?
A. Decreased gluconeogenesis
B. Decreased glycogenolysis
C. Increased glycolysis
D. Increased lipolysis
E. Increased protein breakdown

Answer 23

D

Question 24

A 35 year old woman presents to her GP because she has felt thirsty for the last two months. She has a body mass index of 36 kg/m 2 . She has glycosuria ++ ketones are not detected in the urine and a random blood glucose level is 18 mmol/L (reference range 3.3 – 6.0). Which is the most appropriate next test to investigate the long term control of blood glucose? ``` A. Fasting blood glucose B. Glucose tolerance test (GTT) C. Glycosylated haemoglobin (HbA1c) D. No further investigation is needed E. Repeat random blood glucose in one week ```

Answer 24

C

Question 25

A 45 year old woman has a two month history of weight loss. She feels hot and flushed all the time and has occasional palpitations. She has not changed her diet in the past year. What is the most likely possible initial diagnosis? ``` A. Anorexia nervosa B. Diabetes mellitus C. Hyperthyroidism D. Malabsorption E. Menopause ```

Answer 25

C

Question 26

A 55 year old man with a blood pressure of 180/120 mm Hg is found to have a raised aldosterone level. From where is aldosterone released? ``` A. Adrenal cortex B. Adrenal medulla C. Anterior pituitary D. Distal nephron E. Hypothalamus ```

Answer 26

A

Question 27

``` A 45 year old woman has a three month history of weight loss, dizziness, and lethargy. She has a BP of 100/70 mmHg lying and 75/50 mmHg standing. Blood test results: reference range Sodium 125 mmol/L (133–146) Potassium 6.1 mmol/L (3.5–5.3) Urea 8.5 mmol/L (2.5–7.8) Creatinine 100 µmol/L (60–120) Which is the most likely diagnosis? ``` ``` A. Acromegaly B. Addison's disease C. Adrenal adenoma D. Cushing’s disease E. Cushing's syndrome ```

Answer 27

B

Question 28

A 55 year old man is admitted to the Emergency Department and is found to have diabetes mellitus and is treated with insulin. He refuses to eat and three days after admission he is found collapsed and unconscious with a blood glucose level of less than 1 mmol/L (3.3 – 6.0) What is the most appropriate first line treatment? ``` A. Glucose by mouth B. Intramuscular glucagon C. Intravenous glucose D. Rectal glucose E. Subcutaneous glucose ```

Answer 28

C

Question 29

A 12 year old girl presents to her GP with polyuria and polydipsia. She has lost 5 kg in weight over the last month. Her random plasma glucose level is 22 mmol/L (reference range 3.3 – 6.0). What mechanism is most likely to be responsible for her condition? A. β-cell failure to proliferate B. Auto-immune destruction of β-cells C. Peripheral resistance to the action of insulin D. Excess proliferation of α-cells in Islets of Langerhans E. Spontaneous β-cell apoptosis

Answer 29

B

Question 30

A 30 year old man has gained over 10 kg in weight during the last 6 months. He has central obesity and multiple abdominal striae. His blood pressure is 180/96 mmHg. Which hormone level is most likely to be abnormal in this man? ``` A. Aldosterone B. Cortisol C. Growth hormone D. Testosterone E. Thyroxine ```

Answer 30

B

Question 31

A 45 year old woman has headache, sweating and palpitations. She has a BP of 230/135 mmHg. A CT scan of her abdomen shows a tumour of the adrenal gland. The secretion of which hormone is most likely to be increased? ``` A. Adrenaline B. Adrenocorticotropic hormone C. Aldosterone D. Angiotensin II E. Cortisol ```

Answer 31

A

Question 32

A 40 year old woman presents to her GP saying that she is tired all the time. Her weight has increased by 5 kg over the last year and she has a low mood. Her periods are regular, but heavy. She has a BP of 125/75 mmHg, and urinalysis shows no abnormalities. The measurement of which hormone is most likely to identify the underlying cause? ``` A. Adrenaline B. Cortisol C. Insulin D. Parathyroid E. Thyroid stimulating hormone ```

Answer 32

E

Question 33

A 35 year old woman presents to her GP with increase in weight, constipation, tiredness and irregularity of her menstrual periods. She has a BMI of 37 and complains that her hair has become dry and coarse. Which blood test would confirm the most likely diagnosis? ``` A. Calcium B. Full blood count C. Lipid profile D. Cortisol E. Thyroid function test ```

Answer 33

E

Question 34

A neonate is found to have a positive screening test for hypothyroidism. What thyroid function test results from a blood sample would confirm this? ``` A. Elevated TSH and elevated free T4 B. Elevated TSH and low free T4 C. Low TSH and elevated free T4 D. Low TSH and low free T4 E. Normal TSH and low free T4 ```

Answer 34

B

Question 35

A 65 year old man has a long history of smoking and has lost 4 kg in weight over the past 3 months. A chest radiograph shows a 2 by 3 cm mass in the left lung. Blood test results: Serum calcium 2.86 mmol/L (2.2-2.6) Serum phosphate 0.7 mmol/L (0.8-1.5). What is the most likely explanation of the raised serum calcium level? A. Increased bone turnover due to bone metastases B. Increased parathyroid hormone secretion C. Tumour secretion of peptides structurally similar to parathyroid hormone D. Tumour secretion of peptides that block the parathyroid calcium receptor E. Tumour secretion of peptides that inhibit calcitonin

Answer 35

C

Question 36

A 75 year old woman presents to her GP with a six month history of lethargy, constipation and polyuria. She has a low mood. Blood test results: Corrected calcium 2.90 mmol/L (2.2–2.60) Parathyroid hormone 10.2 pmol/L (1.6–7.5) What is the most likely diagnosis? ``` A. Cushings’ disease B. Hyperparathyroidism C. Hypoparathyroidism D. Type 2 diabetes mellitus E. Vitamin D intoxication ```

Answer 36

B

Question 37

A 55 year old man develops polyuria and polydipsia. He has previously been successfully treated for lung cancer. Blood test results: urea 8.0 mmol/L (2.5–7.8) creatinine 140 µmol/L (60–120) calcium 3.0 mmol/L (2.2–2.6) Which is the most appropriate next biochemical investigation? ``` A. Alkaline phosphatase B. Calcitonin C. Insulin D. Parathyroid hormone E. Phosphate ```

Answer 37

D