L16-18 and 20: Endocrine and Nutritional Diseases

Question 1

Adult human skeleton is composed of ___ bones

Answer 1

106

Question 2

Bone matrix composition

Answer 2

35% organic “osteoid” component (mainly type I collagen)

65% mineral component (extremely hard) - hydroxyapatite; repository for 99% Ca and 85% P

Question 3

Which bone cell type is multi-nucleated?

Answer 3

Osteoclasts

Question 4

Functions of osteoblasts

Answer 4

1. Main Function of osteoblast: secretion of a complex
   mixture of bone matrix proteins (osteoid)
2. Regulate differentiation and activity of osteoclasts
3. Important in maintaining calcium homeostasis

Question 5

T or F: 10% of adult skeleton is replaced annually.

Answer 5

True

Question 6

Essential hormones involved in bone remodelling

Answer 6

GH produced by pituitary stimulates fat production and production of IGF-1 by the liver to stimulate bone remodelling.

Question 7

Wnt, LRP5/6, β-catenin

Answer 7

LRP5/6 activation by Wnt results in migration of β-catenin from cytoplasm to nucleus where it results in transcription of genes important in bone formation

Question 8

Sclerostin

Answer 8

Sclerostin production by osteocytes inhibit osteoblast activation via the Wnt pathway

Question 9

Osteoclast mechanism

Answer 9

Cathepsin K (proteinase) production is responsible for degradation of type I collagen in osteoclast-mediated bone resorption. The osteoclast has a pH of 5, which promotes degradation of bone.

Question 10

Define: Osteopaenia

Answer 10

General reduction in bone density

Question 11

Define: Osteoporosis

Answer 11

Severe form of osteopaenia which increases risk of fracture in normal, autraumatic physical activities

Question 12

Genetic factors involved in osteoporosis

Answer 12

1. Single gene loss-of-function mutation in LRP5

2. Sequence variation in osteoclast regulatory genes RANK, RANKL: low Ca2+ intake increases risk,

Question 13

Menopause pathophysiology in osteoporosis

Answer 13

Decreased serum oestrogen leads to increased levels of IL-1, IL-6 and TNF (proinflammatory), RANK, RANKL, and increased osteoclast activity

Question 14

Ageing pathophysiology in osteoporosis

Answer 14

1. Decreased replicative activity of osteoprogenitor cells
2. Decreased synthetic activity of osteoblasts, increased death of osteoblasts
3. Decreased activity of growth factors
4. Reduced physical activity

Question 15

Why is osteoporosis more common in women?

Answer 15

Oestrogen (E) attenuates osteoclast activity/number therefore resorption of bone, therefore reduction in E activates on osteoclasts & bone resorption. Unlike E, androgen equally affects osteoblast and osteocyte activity – balance retained

Question 16

Paget Disease

Answer 16

Chronic disease characterised by lesions of bone from disordered remodeling, in which excessive bone resorption initially results in lytic lesions tobe followed by disorganized and excessive bone formation.

Question 17

Diffuse Non-toxic (Simple) Goiter

Answer 17

Enlargement of the thyroid caused by impaired synthesis of thyroid hormone, most often the result of dietary iodine deficiency - degree of enlargement is proportional to level and duration. Impairment leads to compensatory ↑ in TSH levels → hypertrophy and hyperplasia of follicular cells → gross enlargement of gland

Question 18

Grave’s Disease aetiology

Answer 18

Excessive production of two thyroid autoantibodies: Thyroid-stimulating Ab, Growth-stimulating Ab. These Ab bind to the TSH receptor and act as ligands, stimulating cell resulting in increased levels of thyroid hormones and hyperplasia of the thyroid gland

Question 19

Diagnosis of hyperthyroidism

Answer 19

Measurement of serum TSH concentration, because its levels are decreased early. Confirmed by high free T4

Question 20

Cretinism

Answer 20

Hypothyroidism that develops in infancy or early childhood. Impaired development of the skeletal system and central nervous system, manifested by severe mental retardation, short stature, coarse facial features, a protruding tongue, and umbilical hernia

Question 21

Myxedema

Answer 21

Hypothyroidism developing in the older child or adult. Generalized fatigue, shortness of breath and mental sluggishness due to reduced cardiac output , which may mimic depression. Decreased sympathetic activity results in constipation and decreased sweating

Question 22

Thyroiditis

Answer 22

Typically acute inflammation of the thyroid gland. Three most common and clinically significant subtypes:

1. Hashimoto thyroiditis
2. subacutelymphocytic thyroiditis
3. granulomatous(de Quervain) thyroiditis

Question 23

Hashimoto thyroiditis

Answer 23

Painless enlargement of the thyroid, low T4 & T3, sometimes preceded by thyrotoxicosis (high T3 & T4). CD8+ cytotoxic T cells destroy thyroid follicular cells via FasL receptor present on the T cell.

Question 24

Granulomatous Thyroiditis

Answer 24

Virus-initiated. Histologically distinct – presence of multinucleated ‘Giant Cells’

Question 25

Mechanism of regulation of calcium homeostasis by the parathyroid glands

Answer 25

Decreased levels of Ca2+ stimulate the synthesis and secretion of PTH. PTH activates osteoclasts (Ca2+ and P released into the blood), increases calcium reabsorption from food, and promotes activation of Vit D, which further increases calcium absorption from food. Rising Ca2+ in the blood inhibits PTH release

Question 26

Genetic polymorphism in hyperparathyroidism

Answer 26

Cyclin-D1 gene inversions leading to overexpression of cyclin-D1 in the parathyroid cells.

Question 27

Composition of the adrenal gland

Answer 27

Medulla (inner part) constitutes 20% of the gland and the cortex (outer part) constitutes 80%. Cortex consists of three zones. The medulla and each of the zones in the cortex produce different hormones.

Question 28

Zona glomerulosa

Answer 28

Outermost zone of the adrenal cortex that secretes mineralcorticosteroids, hormones important for fluid homeostasis, e.g. Aldosterone which regulates absorption/uptake of K+ and Na+ levels in the kidney

Question 29

Zona fasciculata

Answer 29

Middle zone of the adrenal cortex that secretes glucocorticoids important for macronutrient metabolism, e.g. Cortisol which raises blood glucose and cellular synthesis of glycogen.

Question 30

Zona reticularis

Answer 30

Innermost layer of the cortex, secretes sex hormones (androgens), and small amounts of glucocorticoids

Question 31

Adrenal medulla

Answer 31

Composed of functional units - the chromaffin cell which functions as a neuroendocrine cell. In response to stimulation chromaffin cells secrete adrenaline and noradrenaline directly into blood.

Question 32

ACTH is produced from which precursor

Answer 32

POMC

Question 33

Initial precursor of glucocorticoids, mineralocorticoids, and androgens

Answer 33

Cholesterol

Question 34

Glucocorticoid action

Answer 34

1. Increasing glycogen synthesis in the liver and decreasing of glucose utilisation by peripheral tissues. Increase in gluconeogenesis.
2. Increasing protein synthesis in the liver and decreasing of its synthesis in muscles and increasing of protein destruction in muscles.
3. Increase in lipolysis.
4. Anti-inflammatory function and immmunomodulation
5. Cardiovascular regulation (increase in blood pressure)

Question 35

Mineralocorticoid action

Answer 35

Regulation of electrolyte balance - mainly Na+:
Angiotensinogen (produced in the liver) is converted to angiotensin I by renin (produced by the kidney). ACE (released from the lungs) convertes angiotensin I to angiotensin II which acts on the adrenal gland to stimulate release of aldosterone, as well as directly on blood vessels to stimulate vasoconstriction. Aldosterone acts on the kidneys to stimulate reabsorption of salt and subsequently water.

Question 36

Waterhouse-Friderichsen syndrome

Answer 36

Primary acute adrenocortical insufficiency - massive bacterial infections, rapid hypotension - shock, intravascular coagulation - seen in skin
Rapid adrenocortical failure

Question 37

Addison disease

Answer 37

Primary chronic adrenocortical insufficiency caused by gradual destruction of the adrenal cortex mostly due to autoimmune adrenalitis (destruction of steroidogenic cells) - autoantibodies against steroidogenic enzymes 21/17-hydroxylase.
Can also be caused by metastatic neoplasia of adrenal, mainly from primary lung and breast cancer or infections such as TB.

Question 38

Cushing syndrome

Answer 38

Constellation of signs and symptoms caused by prolonged excessive amounts of circulating glucocorticoid.
Aetiology: mostly result from exogenous administration of GCs “iatrogenic”. Endogenous aetiology can be ACTH-dependent or independent

Question 39

In cases where endogenous GCs cause Cushing, bilateral cortical ____ occurs

Answer 39

hyperplasia

Question 40

In patients where exogenous GCs cause Cushing,
suppression of ACTH occurs leading to bilateral
cortical _____

Answer 40

atrophy

Question 41

Clinical features of Cushing

Answer 41

Obesity, thin and fragile skin with pinkish striae, hypertension, proximal muscular weakness affecting
predominantly the muscles of the pelvic girdle, acne, hirsutism, and menstrual irregularities, osteoporosis, compression fractures and persistent back pain, peripheral oedema, psychiatric manifestations, including anxiety, depression, rarely psychotic episodes

Question 42

Treatment for Cushing

Answer 42

Surgery, pituitary irradiation, pharmocologic therapy

Question 43

Define: Obesity

Answer 43

Pathological fat excess. BMI of 30 or higher