Target Qs

Question 1

Bone modeling vs. bone remodeling

Answer 1

Bone modeling:
1. Formation of new bone at one site and removal of the old bone from another site in the same bone
2. Changes the size and the shape of the bone
3. Bone growth occurs

Bone remodeling:
1. Small amount of bone on the surface of the trabeculae or in the interior of the cortex is removed and then replaced at the same site
2. Does not change the size in the shape of the bone
3. Removes micro-cracks, defects, old bone (no bone growth occurs)

Question 2

Advantages of bone remodeling

Answer 2

1. Repairs local damage
2. Restores bone strength
3. Function of the skeleton as a bank for calcium and phosphorus

Question 3

Describe the biochemical basis of how a menopausal woman develops osteoporosis with osteopenia

Answer 3

1. After menopause women are at increased risk of developing osteopenia and osteoporosis
2. Due to hormonal changes there is mainly a decrease in estrogen levels
3. Normally, estrogen has a dual effect on bone metabolism
4. It favors bone formation by increasing no. and function of osteoblasts
5. Then it reduces bone resorption
6. Estrogen deficiency can decrease osteoblast function, resulting in reduced bone formation
7. Estrogen affects the balance of RANKL and its receptor
8. RANKL promotes osteoclast formation and increases bone resorption
9. } Bone mass and density is decreased causing osteopenia and osteoporosis

Question 4

Explain why menopausal women at risk of osteoporosis are treated with estrogen progesterone therapy

Answer 4

1. Provides estrogen hormone
2. Estrogen helps to preserve bone mass by slowing down the activity of osteoclasts, which are the cells responsible for breaking down bones
3. This process reduces the rate of bone loss

Question 5

Name five constituents of polymerase chain reaction (PCR)

Answer 5

1. DNA template
2. Bacterial Taq /DNA polymerase
3. Two polymers
4. Deoxynucleoside triphosphate
5. Buffer solution

Question 6

Explain the main steps of PCR with the relevant temperatures

Answer 6

1. Denaturation → separates the target DNA by breaking the hydrogen bonds (90 - 95°C)
2. Annealing → binds the primers to the target DNA sequence (50 - 65°C)
3. Extension → makes new DNA copies (70°C)

Question 7

State 2 applications of PCR

Answer 7

1. Comparison of a normal gene to its mutant form
2. Forensic analysis of DNA sample

Question 8

Explain the difference between western blotting and ELISA

Answer 8

1. ELISA and western blotting are both laboratory techniques used to detect and quantify proteins
2. Have differences in their method and some applications
3. Western blotting:
   → Protein separation
   → Sample preparation and gel electrophoresis
   → Protein transfer
   → Blocking + antibody probing and detection
4. ELISA:
   → take testing microplates and then add the antibody
5. Specificity of western blotting is higher than ELISA

Question 9

Investigations to diagnose type two diabetes mellitus

Answer 9

1. Fasting blood glucose level:
   Normal = <5.5 mmol/dl
   Prediabetes = 5.6 - 6.9 mmol/dl
   Diabetes = >7 mmol/dl
2. HbA1c is non-enzymatic glycation of hemoglobin:
   Normal = < 6%
   Pre-diabetes = 6% - 6.4%
   Diabetes = > 6.5%
   → Patient does not have a good glycemic control for past 2 to 3 months
3. According to the given investigations fasting blood glucose level, HbA1c and serum triglyceride levels were increased
4. } Patient has type two diabetes mellitus

Question 10

Explain the reason for increased frequency of urination in a patient with type two diabetes mellitus

Answer 10

1. Glucose is a highly osmotically active compound
2. When plasma filters through the glomerulus, glucose also filters through it
3. Almost all glucose is absorbed to the blood in the renal tubules
4. When glucose levels in the plasma exceed more than the renal threshold, glucose starts to appear in urine
5. As glucose is a highly osmotically active compound, it increases the osmolarity of urine
6. } More water is dragged and retained in the renal tubules causing increased urine output
7. Leads to frequent urination

Question 11

Explain the biochemical basis for increased serum triglyceride levels in a patient with type two diabetes mellitus

Answer 11

1. Type 2 diabetes mellitus is caused by insulin resistance
2. Normally, insulin inhibits HSL and inhibits the breakdown of lipids + decreases release of FFAs into the bloodstream
3. Insulin also activates LPL and hydrolyses TAGs in the circulating lipoproteins
4. In insulin resistance, HSL is activated and LPL is inhibited
5. Leads to increased lipolysis and release of FFAs into the bloodstream causing the elevation of serum TAG level

Question 12

Describe the mechanism of action of different adrenergic receptor subtypes

Answer 12

1. Adrenaline, noradrenaline, dopamine and some therapeutic drugs act on adrenergic receptors
2. Receptor specificity and affinity of these hormones to adrenergic receptors are varied
3. Adrenergic receptors are found on the cell surface (G protein coupled receptors)
4. Alpha 1,2 + Beta 1,2,3
5. Alpha 1 receptors:
   → Coupled with Gq proteins, leads to activation of phospholipase
   → IP3 and DAG is formed
   → Second messengers increase the release of Ca2+ ions, smooth muscle contraction occurs
6. Alpha 2 receptors:
   → Coupled with Gi proteins, activates adenylate cyclase + decreases the activation of CAMP
   → Reduced CAMP levels lead to smooth muscle contraction
   → Decreases Ca2+ levels and inhibits neurotransmitter release from the neurons
7. Beta receptors:
   → Coupled with Gs proteins, activates adenylate cyclase
   → Leads to increased CAMP levels + increased glycogen breakdown
   → Smooth muscle relaxation + cardiac muscle contraction occurs

Question 13

Explain how catecholamines ensure an adequate supply of metabolic fuel to skeletal muscles during the “fight or flight” response

Answer 13

1. The fight or flight response is a sympathetic response
2. It is mainly facilitated by the actions of catecholamines released from the adrenal medulla and from the ends of neurons
3. Catecholamines increase the FFA levels, glucose levels in the blood
4. Vasodilation in blood vessels to the muscles
5. Vasoconstriction in vascular beds that supply the gut and skin (to increase blood supply to the muscles)
6. Catecholamines further stimulate the liver to increase glycogenolysis and gluconeogenesis to increase glucose levels required to facilitate muscle movements
7. Also inhibits glycolysis in the liver
8. Increases FFA level in the blood and stimulates lipolysis in the adipose tissues

Question 14

Explain the biochemical basis of how excessive iodine intake leads to primary hyperthyroidism

Answer 14

1. Iodine is essential to produce thyroid hormone
2. Thyroid hormone synthesis:
   ① Iodine uptake via Na+/I- symporter (energy dependent)
   ② Oxidation takes place in the cell by thyroperoxidase (haem containing enzyme)
   ③ In the cell, thyroglobulin protein is synthesized and exocytosed into the colloid
   ④ Iodination occurs where iodine binds to the thyrosine molecules in the thyroglobulin protein (done by thyroid peroxidase)
   ⑤ Coupling occurs which forms T4 and T3
   ⑥ Secretion into the blood occurs
3. Thyroid hormone secretion is regulated by TSH which is secreted by ANT pituitary
4. Secretion of TSH is regulated by TRH via the hypothalamus
5. Excess iodine leads to production of more T3 and T4
6. Due to negative feedback mechanism TSH secretion is inhibited
7. } Excessive iodine intake can lead to primary hyperthyroidism