Chemical Pathology

Question 1

What are the 3 hormones that are secreted by the thyroid?

Answer 1

T4
T3
Calcitonin- used as a tumor marker in TCA

Question 2

What is the pathogenesis of congenital hypothyroidism?

Answer 2

Defect in metabolic steps of Thyroid hormones.

Question 3

What is the mechanism for carbimazole?

Answer 3

interferes with biosynthetic steps of an overactive thyroid

Question 4

Explain the difference between T3 and rT3.

Answer 4

T3- is the active form of T4, resulting from the deiodination of T4’s outer ring.
rT3- reverse T3 is an inactive form, resulting from the deiodination of the inner ring.

Question 5

In what conditions are the rT3 formed?

Answer 5

Starvation, severe illness
-limit bodies energy expenditure

Question 6

How does T3 perform its function?

Answer 6

Enters the cell and binds to receptors in the nucleus
upregulates expression of genes
increase sensitivity to hormones, such as CVS and NS to catecholamines, enhances insulin action

Required for metabolic activity- O2 consumption and ATP hydrolysis increase (mitochondria)

Question 7

Why does a person remain euthyroid despite the change in a TBG?

Answer 7

When TSH levels increase, more TBG is produced, leading to an increase in total T4 levels. Conversely, when TSH levels decrease, less TBG is produced, leading to a decrease in total T4 levels.

However, it is important to note that only the free, biologically active form of T4 is able to exert its effects on the body. Therefore, even if the total T4 level increases or decreases due to changes in TBG levels, as long as the level of free T4 remains within the normal range, the patient will remain euthyroid (meaning their thyroid function is normal).

Question 8

Explain how the total level of thyroid hormone can be misleading.

Answer 8

Thyroid hormones (T4 and T3) are transported in the bloodstream by binding to a carrier protein called thyroxine-binding globulin (TBG). However, certain drugs can compete with thyroid hormones for the binding sites on TBG, thereby reducing the effective concentration of TBG. This competition can result in a decrease in the level of total thyroid hormone in the blood, even though the amount of free hormone may remain unchanged.
Measuring total thyroid hormone alone can be misleading because it does not account for changes in TBG concentration or the amount of hormone that is bound to the protein. Measuring free hormone levels directly provides a more accurate reflection of the amount of thyroid hormone available to the body.

Question 9

What affects TBG levels?

Answer 9

Increase
estrogen
-Oral con pill
-pregnancy

Decrease
Protein-losing states
Malnutrition
Costicosteroids

Question 10

What are the Thyroid Cancer markers?

Answer 10

Thyroglobulin (anti-thyroglobulin Abs)
-papillary and follicular
Calcitonin
-Medullary

Question 11

Which conditions can be missed if you test TSH assay?

Answer 11

Secondary Hypothyroidism and sick euthyroid syndrome.

Question 12

Explain what happens between TSH and fT4 in graves disease.

Answer 12

Graves treated with radio-iodine and antithyroid TSH responds slowly to therapy
overtly low fT4 (hypothyroid)
TSH is still-suppressed
Thyrotoxicosis

Question 13

What are the symptoms of hyperthyroidism?

Answer 13

Weight loss, sweating, heat intolerance, fatigue
Tachycardia, atrial fibrillation, angina, high output cardiac failure
Agitation, tremor, generalized muscle weakness, proximal myopathy
Diarrhoea, oligomenorrhoea, infertility, goitre Eyelid retraction, proptosis, diplopia (Grave’s disease)

Question 14

Explain the pathogenesis of graves disease.

Answer 14

Ab to TSH receptor mimics TSH
Activation and constant stimulation of gland and producing of thyroxine
Pituitary TSH suppressed.

Question 15

What are the laboratory results for graves disease?

Answer 15

High Plasma concentration of T3 + T4
Totally suppressed

Question 16

What are the clinical features of graves disease and how do they manifest?

Answer 16

Proptosis- bulging eyes, thickening of retroorbital muscles
pre-tibial myxoedema- swelling of soft tissues.

Question 17

Explain how Gestational Trophoblastic disease causes hyperthyroidism.

Answer 17

Tumour from trophoblastic tissue
Increase HCG
Cross reacts with TSH, Overlapping activity of the alpha globin (same as TSH)
TSH was suppressed and T4 increased

Question 18

Describe the thyroid storm.

Answer 18

Acute presentation of thyrotoxicosis
hyperpyrexia
dehydration
cardiac failure

Question 19

What are the causes of hypothyrodism?

Answer 19

Autoimmune hypothyroidism
Atrophic thyroiditis
Hashimoto’s thyroiditis goitre
Iatrogenic
* Post surgery, radioactive iodine, antithyroid drugs
Rare 2 ° hypothyroidism (N/↓TSH) Enzyme defects * Iodine deficiency

Question 20

What are the thyroid function test results?

Answer 20

TSH high
T3 and T4 Low

Prolactin High due to TRH
Cholesterol High
CK high

Question 21

What is the complication of congenital hypothyroidism?

Answer 21

Mental retardation

Question 22

Explain sickle euthyroid syndrome.

Answer 22

Typically, during the acute phase of a serious illness, fT3 and, less often, fT4 concentration drops below normal. TSH is usually normal but may be low in the severely ill. Possible explanations include decreased peripheral conversion of T4 to T3, and inhibition of TSH secretion by cortisol.

Question 23

Explain the relationship between exercising and insulin

Answer 23

It increases the uptake of glucose in muscles

Question 24

Describe obesity and overweight.

Answer 24

BMI of
25-30 overweight
30-40 Obese

Question 25

what is leptin and describe its function?

Answer 25

Long-term energy balance cytokine
Released from adipocytes
shows the brain the peripheral fat stores
Increases energy expenditure
Promote fecundity (GnRH)- hence thin women do ovulate

Question 26

What is the problem with Long term Energy balance in obese patients?

Answer 26

Due to the upregulation of SOCS3- inhibition/resistance of/to insulin and leptin

Question 27

Describe Glucagon-like Peptide 1.

Answer 27

Ileum
Short chain FA (bacteria produces) and glucose binds to L-type cells
Release GLP1
-inhibits gastric
-stimulates insulin
-improves insulin sensitivity
- anorexigenic effect on

analogs used to treat diabetes and obesity

Question 28

Describe Oxyntomodulin (OXM).

Answer 28

L-type cells
same stimuli as GLP1
acts on the arcuate nucleus in hypothalamus to suppress appetite

Question 29

Describe PYY.

Answer 29

distal ileum and colonic enterocytes
pre-synaptic Y-2 receptors in hypothalamic AN
inhibit Neuropeptide Y (that stimulates hunger)

Question 30

Why is appetite decreased in malabsorption?

Answer 30

Food reaches further parts of the intestine and stimulates Satiety peptides, hence unrefined foods that slowly digest keeps you fuller for longer.

Question 31

How do the paraventricular nucleus control appetites and energy expenditure?

Answer 31

MSN- reduce A and increase E
NPY- opposite

Question 32

Explain the issue with the hypothalamus in obese people.

Answer 32

have a hypothalamus that thinks they are too thin and so regulates their appetite and energy expenditure to maintain their body weight at a higher set point.

Question 33

Describe a Roux y Gastric Bypass.

Answer 33

Smaller stomach
-limits meals and allows for satiety

By-pass allows food to pass directly into the distal bowel, stimulating satiety peptides.

Question 34

Describe a Roux y Gastric Bypass.

Answer 34

Smaller stomach
-limits meals and allows for satiety

By-pass allows food to pass directly into the distal bowel, stimulating satiety peptides.