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Metabolic Endocrinology > Midterm 2 Review > Flashcards

Midterm 2 Review Flashcards

1
Q

How does the blood flow to the thyroid follicles?

A

It flows to regulate T4/T3 release by affecting the delivery of TSH, iodine and nutrients

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2
Q

What are the inactive forms of T4 and T3 respectively?

A

rT3 and T2 are formed in peripheral tissues

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3
Q

What are the steps required for T4/T3 synthesis?

A
  1. Trapping: active transport of iodine into thyroid cell
  2. Organification: oxidation of iodide and iodination of tyrosyl residues in thyroglobulin
  3. Coupling: Liking pairs of iodotyrosines in thyroglobulin to form T3/T4
  4. Proteolysis of TG to release T3/T4
  5. Deiodination of iodotyrosines in thyroid cell and recycling of I
  6. Intrathyroidal 5’-deiodination of T4/T3
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4
Q

What are 3 things that are necessary to thyroid hormone synthesis?

A

NIS (Na+/I- symporter), TG (thyroglobulin), TPO (thyroid peroxidase)

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5
Q

What are the effects of TSH?

A
  • Growth: increased DNA,RNA, protein, phospholypid synthesis, Increased cell size, number and follicle formation
  • Synthesis of hormone: increased synthesis of T4/T3, increased glucose oxidation and NADPH generation
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6
Q

What can inhibit iodine uptake and thyroid tissue?

A
  • Anions like ClO4- (perchlorate) block the uptake of iodine = can be used to block hyperthyroidism
  • Radioactive idoine (oral I131) can be used to destroy thyroid tissue (for hyperthyroidism)
  • Bromide and nitrite are competitive inhibitors, can cause apparent iodine deficiency in some areas of world
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7
Q

How is thyroglobulin synthesized?

A
  • TSH stimulates its transcription/translation in follicular cells
  • Extensively glycosylated in Golgi
  • Packed in vesicles to be exocytosed into lumen of follicle
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8
Q

How do iodination-inhibiting drugs work?

A
  • Thyroperoxidase = targeted by many drugs to reduce thyroid hormone production
  • Goitrogens are inhibiting compounds found in foods like milk from cows fed certain plants (i.e. brassicae)
  • -> blocking iodination = increased TSH production resulting in hyperplasia and goiter
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9
Q

What part of the thyroglobulin molecule becomes iodinated?

A

Tyrosines

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10
Q

What molecule catalyzes coupling?

A

TPO (MIT+DIT = T3, DIT + DIT = T4)

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11
Q

What do the kinetics of thyroid hormone synthesis do?

A

They make sure there are steady levels of active T3 despite fluctuations in dietary intake of iodine

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12
Q

How can thyroid hormones (lipophilic) be carried around?

A

Bound to carrier proteins synthesized by the liver: TBG (thyroxine binding globulin), transthyrethin, albumin

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13
Q

What happens with drugs and carrier proteins?

A

some drugs will compete with binding to carrier protein = elevated free T4/T3 = hyperthyroidism as a side effect

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14
Q

True or False: T3 is 2-10 times less active than T4

A

False! it is 2-10 times MORE active than T4

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15
Q

In what form can cells take up thyroid hormones?

A

In the free form, so no carrier proteins = free hormone concentration is important (by measuring levels of binding proteins)

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16
Q

What are the 3 different deiodination reactions of T4?

A

Type 1: T4–> T3 in liver, kidney, muscle.
Type 2: T4–>T3 in brain, pituitary, key for feedback on TRH and TSH
Type 3: T4–>rT3 if T3 already in excess and T3–>T2

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17
Q

What are the 3 deiodinases?

A
  • D1&D2: bioactive thyroid hormone by removing a single outer-ring iodine atom
  • D3: inactivates thyroid hormone by removing a single inner-ring iodine atom (T4/T3:rT3/T2)
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18
Q

How are thyroid hormones involved in thermogenesis?

A

T2 binds to cytochrome C to increase oxidative phosphorylation
T3 binds to uncoupling proteins to increase heat production + TR to increased mitochondrial transcription

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19
Q

What are the physiological effects of thyroid hormones?

A
  • Heart: increased strength of heart beat
  • Adipose tissue and muscle: catabolic
  • Bone and nervous system: developmental
  • Gut and lipoprotein: metabolic (more CHO absorption and formation of LDLr)
  • Other: calorigenic
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20
Q

What are the effects of TH on the cardiovascular system?

A
  • Rise in body temp
  • Cutaneous vasodilation = decreased resistance to peripheral blood flow = increase of renal NA+ and H2O reabsorption to expand blood volume
  • Increase cardiac output
  • alpha-myosin heavy chain, sarcoplasmic reticulum Ca ATPase, Beta-adrenergic receptors, G-protein, Na+-K+ ATPase, some K+ channels are turned on
  • NET RESULT: increased heart rate and force of contraction
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21
Q

What is used to treat thyroid storms?

A

Thyroid storms= TH toxicity due to infection, trauma, drugs,etc.
Treated using Beta-blockers

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22
Q

What are the effects of hyper/hypothyroidism on skeletal muscle?

A

Hyper: muscle weakness bc of pro catabolism
Hypo: muscle weakness, cramps, stiffness

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23
Q

What are the effects of THs in growth and tissue development?

A
  • increased growth and maturation of bone
  • increased tooth development and eruption
  • increase growth and maturation of epidermis, hair follicles and nails
  • increased rate and force of skeletal muscle contraction
  • inhibits synthesis and increases degradation of mucopolysaccharides in subcutaneous tissue
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24
Q

What is myxodema and what can cause it?

A

Myxodema = puffiness associated with accumulation under skin

caused by hypothyroidism

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25
Q

What are the 4 types of hypothyroidism?

A
  • primary: thyroid gland failure (most common) –> low free T4, high TSH
  • secondary: pit. failure (TSH deficiency) –> low free T4, low TSH
  • tertiary: hypothalamic failure (TRH deficiency)
  • peripheral resistance to TH action
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26
Q

What is the Tx for hypothyroidism?

A

Levothyroxine (T4) due to longer half-life to prevent bone loss, cardiomyopathy and myxedema

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27
Q

What is cretinism?

A

It is caused by iodine deficiency during pregnancy. It can easily be prevented by iodine supplements.

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28
Q

What happens to GH secretions in hypothyroid children?

A

GH secretions are depressed. T3/T4 potentiate the effect of GH on tissues

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29
Q

What are side effects of hypothyroidism in infants?

A
  • mental retardation
  • stunted growth
  • delayed puberty
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30
Q

What are possible causes of hypothyroidism?

A
  • maternal iodine deficiency
  • fetal thyroid dysgenesis
  • inborn errors of thyroid hormone synthesis
  • maternal antithyroid antibodies that cross the placenta
  • fetal hypopituitary hypothyroidism
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31
Q

What is myxedema coma?

A

untreated hypothyroidism which occurs typically in older patients during the winter : progressive weakness, hypoventilation, hypoglycemia, hypothermia (24 C) eventually progressing to coma and death. Elderly are more susceptible in the winter.

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32
Q

What is Hashimoto’s disease?

A
  • (Autoimmune) Immune system attacks and gradually destroys the thyroid gland
  • Circulating antibodies against antigens present in the thyroid
    and infiltration by lymphocytes gradually interfere with normal thyroid function
  • Usually against TPO(&/or TG) = antibody development for TPO, TG and low T4, high TSH levels
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33
Q

What is Grave’s disease?

A

Hyperthyroidism due to an over-production of THs, causing enlargement of thyroid and other symptoms like exophtalmos, heat intolerance and anxiety.
Immune system producing anti-TSH receptor antibodies: binding of Ab to receptor induces signal transduction of TSH pathway resulting in T4 i.e. TSH not required

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34
Q

What are Tx for Grave’s disease?

A

Medical – anti-T4 compounds (Propothyouracil, Methimazole, Propranolol)
Surgical – Subtotal Thyroidectomy
Radiation

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35
Q

True or false: Hyperthyroidism can also be caused by T4 secreting tumours but very rarely for TSH secreting tumours

A

True!

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36
Q

What are remedies for rickets (softening and bending of bones)?

A
  • Fish liver oil
  • Sun exposure
  • UV-irradiation of certain foods
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37
Q

What are some of calcium’s roles?

A
  • skeleton
  • blood clotting
  • enzyme activity
  • membrane excitability
  • second messenger
  • muscle contraction
    • intracellular levels are about 1/1000 fold lower than extracellular
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38
Q

How much calcium is bound to albumin, complexed to citrate and free?

A

50% albumin, 8% citrate, 42% free ionized Ca2+

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39
Q

Why does a disequilibria induce tetany?

A

it is the induction of tetany by overbreathing (hyperventilation). it reduces the partial pressure of CO2. Less H2CO3 is produced and H+ falls → alkalosis. To compensate, H+ is released from serum proteins, and bind Ca++. Reduction in free serum Ca++ = tetany (extensive spasm of skeletal muscle)

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40
Q

What cells produce calcitonin, to reduce serum calcium?

A

Parafollicular or c-cells

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41
Q

What cells detect calcium ECF concentrations?

A

Calcium sensing receptors (CaR) located on cell membranes of chief cells

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42
Q

How is the parathyroid made?

A

From preproPTH, then proPTH, the PTH with amino terminus and carboxy terminus
it is a highly conserved hormone with a short half-life (2-4 minutes).

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43
Q

What happens to cAMP production with certain calcium []s?

A
  • Decreased cAMP production when high Ca concentrations (increased IP3)
  • Increased cAMP production when low Ca concentrations (decreased IP3)
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44
Q

Where are calcium receptors?

A

On the parathyroid cells (G-protein complex)

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45
Q

How does calcium regulate PTH release?

A
  • High calcium will activate G-protein IP3 signalling to decrease PTH
  • Low calcium will activate G-protein cAMP signalling to increase PTH
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46
Q

What organs (3) does PTH target?

A
  • Bone (resorption)
  • Kidney (increase Ca2+ reabsorption)
  • Gut (increased Ca2+ absorption)
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47
Q

What can be used as an index of bone resorption activity?

A

Pyridinoline (collagen breakdown product) in urine

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48
Q

Are osteoclasts used in rapid responses to calcium homeostasis?

A

No, they have a slow response, so aren’t involved in accute regulation of calcium homeostasis

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49
Q

What hormones act on osteoblast to produce osteoclast-activating factors?

A

PTH, calcitriol, and PGE2. they stimulate bone-matrix resorption by osteoclasts

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50
Q

What is PTHrP (parathyroid related protein)?

A

similar structure to PTH and can bind to PTH receptor but produced by many tissues in fetus and adult. required for normal development as a regulator of the proliferation and mineralization of chondrocytes and regulator of placental Ca++ transport.

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51
Q

How many G-protein receptors exists for PTH?

A

2: PTHR-1 (bone and kidney Gs) binds PTH and PTHrP with equal affinity
PTHR-2 binds only PTH

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52
Q

How does estrogen impact osteoclast activity?

A

Estrogen down-regulates osteoclast activity. Low [estrogen] will increase osteoclast activity.

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53
Q

What characterizes hyperPTism?

A

increased parathyroid cell proliferation and PTH secretion which is independent of calcium levels.

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54
Q

What are the common causes of hyperPTism?

A

Enlargement of a single gland or parathyroid adenoma in approximately 80% of cases, multiple adenomas or hyperplasia in 15 to 20% of patients and parathyroid carcinoma in 1% of patients

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55
Q

What is the treatment for hyperPTism?

A

removal of affected parathyroid gland: in patients with hyperplasia usual to remove 3.5 glands – parathyroid tissue often autotransplanted
to arm muscle (starts to produce PTH after 3-4 weeks: easier to surgically adjust am’t produced)
or remove abnormal glands if parathyroidadenomas

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56
Q

How does PTH work in osteoporosis Tx to increase bone density?

A

PTH induces RNX2 expression in osteoblasts, increases osteoblast numbers.

57
Q

How does hypoPTism occur?

A

may originate from failure to secrete PTH,
altered responsiveness to PTH, Vit. D deficiency or a resistance to Vit. D.
Problems with PTH may arise from surgery, familial causes, autoimmune disorders or idiopathic causes

58
Q

What is the Tx for hyperPTism

A

Calcium and some form of vitamin D

59
Q

What is the major clinical symptom in hypoPTism?

A

tetany (increased neuromuscular excitability)

60
Q

What is CGRP (calcitonin gene related protein)?

A

made predominantly in the nervous system and may act as a neurotransmitter. CGRP also acts as very potent vasodilator via GPCR receptor

61
Q

How does calcitonin work?

A

reduces plasma Ca2+ primarily through actions on bone and kidney
i.e. osteoclasts have calcitonin receptors (G protein coupled: Gs)
and are inhibited by binding of calcitonin (reduced bone resorption)

62
Q

Is calcitonin essential to Ca homeostasis?

A

No

63
Q

What does a vitamin D deficiency lead to?

A

Deficiency leads to bone defects and the disease rickets

which causes bone deformations and loss of calcium and phosphate from the bones.

64
Q

From which compound can vitamin D be formed in the skin?

A

7-dehydrocholesterol in a Rx requiring sunlight

65
Q

What is vitamin D converted to in the liver and kidney?

A

a hormone, called cholecalciferol (or vit. D3), that regulates calcium uptake.

66
Q

What is food fortified with for extra vitamin D?

A

with vitamin D2, used in margarine and milk

67
Q

Can toxic levels of D3 be achieved by sunlight exposure?

A

No!

68
Q

How does vit D circulate?

A

Bound to vitamin D binding protein (DBP: 85%) or albumin (15%)

69
Q

What is 1-hydroxylase responsible for in the kidney?

A

it yields the biologically active 1,25-dihydroxyvit D3

70
Q

what is 24-hydroxylast responsible for in the kidney?

A

it yields 24,25-dihydroxyvit D3 (unknown role)

71
Q

What are the main circulating derivates of vit D?

A

25-OH-cholecalciferol (made in liver) and calcitriol (made in kidney)

72
Q

What is the main effect of vitamin D3?

A

Promotes intestinal absorption of Ca2+ and PO43-

73
Q

What does vitamin D cause when it binds to its receptor?

A
  • Osteoblast activity (mineralization)
  • Osteoclast activity
  • Intestinal Ca2+/PO43-absorbtion
  • Renal vitamin D degradation (catabolism)
  • Parathyroid hormone synthesis
74
Q

What are the foods that contain the most vitamin D?

A

Swordfish, sardines, mackerel, salmon, herring, tuna

75
Q

Where is calcium most absorbed in the GI tract?

A

illeum! with 13% of intake absorbed.

76
Q

What kind of uptake does calcitriol promote?

A

Active calcium uptake in the intestine by maintaining a calcium gradient. (using myosin/calmodulin complex)

77
Q

What can cause vitamin D toxicity?

A

overdose either therapeutically or accidently

difference in storage, catabolism, absorption among individuals influences level req’d to be toxic.

78
Q

What are symptoms of vit D toxicity?

A

weakness, lethargy, headaches, nausea, polyureia due to hypercalcemia and hypercalciuria – may lead to ectopic calcification etc. (kidneys, blood vessels, heart, lungs, skin) with chronic overuse

79
Q

What Tx is used in vit D toxicity?

A

reduced calcium intake and (Vit. D), rehydration and cortisol (antagonizes action of Vit. D on gut absorption of calcium) + time (slowly cleared from the body)

80
Q

What causes vitamin D deficiency?

A

inadequate sunlight, nutrition or malabsorption (up to 50-60 % of elderly expecially if institutionalized)

81
Q

What can result from vitamin D deficiency?

A
  • rickets (children)

- osteomalacia (adults)

82
Q

What stimulates and suppresses CRH (corticotropin-releasing hormone)?

A
  • Stimulates: low plasma cortisol levels, hypoglycemia, pyrogen and stress
  • Suppresses: high plasma glucocorticoid level
83
Q

What is the adrenal gland’s structure?

A

It is encapsulated with fibrous tissue, and is divided into functional layers
cortex = 90% of mass, inner medulla = 10%
cortex has 3 zones = zona fasciculata is the thickest (75%)

84
Q

What does each zone of the adrenal cortex and the medulla produce?

A

from top to bottom:

  • zona glomerulosa: mineralcorticoids like ALDOSTERONE
  • Zona fasciculata: glucocorticoirds like CORSTISONE, CORTISOL AND CORTICOSTERONE
  • Zona reticularis: sex hormones like ANDROGENS AND ESTROGENS
  • MEDULLA: catecholamines such as NOREPINEPHRINE AND EPINEPHRINE
85
Q

What is particular of the adrenal tissue?

A

Tissue specificity of the reactions in steroid biosynthesis. i.e. zona glomerulosa lacks 17alpha-hydroxylase = can’t synthesize either cortisol or androgens, only aldosterone. This enzyme is found in the zona fasciculata and reticularis.

86
Q

Explain steroid hormone synthesis.

A

cholesterol is the basis of steroid hormone synthesis. In the example of aldosterone:
StAR protein is a rate limiting enzyme to bring cholesterol into the mitochondrion to be converted to pregnenolone by P450scc. This molecule is then shuttled back out into the cytosol, where it becomes progesterone, then deoxycorticosterone, the back in the mitochondrion, it is converted to corticosterone and aldosterone, and delivered out by the cytosol.

87
Q

What step is common to all steroids?

A

Cholesterol –> pregnenolone by StAR (uptake in mito) and P450scc (side chain cleavage)

88
Q

How is StAR protein modulated?

A

StAR is cAMP-inducible and increases in response to trophic hormones (anterior pit. hormones) = ACTH in adrenal gland and gonadotrophins in gonads

89
Q

What effects does cortisol have?

A
  • CHO and protein metabolism

- Anti-inflammatory effects

90
Q

How is cortisol inactivated?

A

By hydroxysteroid dehydrogenase type 2, is tissue specific (cortisol (active) –> cortisone (inactive))
–> type 1 catalyses the reverse reaction, and is tissue specific

91
Q

What other receptor can cortisol activate?

A

The aldosterone receptor! cortisol needs to be inactivated by aldosterone responsive cells in order to respond specifically to aldosterone

92
Q

What can happen if there is an enzyme deficiency in cortisol –> cortisone?

A

AME syndrome (apparent mineralcorticoid excess)

93
Q

What tissues have HSD type 1 enzyme?

A

skin! can convert cortisone in cream to cortisol, as well as liver, adipose, CNS and placenta

94
Q

What tissues have HSD2 enzyme?

A

Kidney, Colon, Sweat gland, salivary gland, placenta (cortisol –> cortisone)

95
Q

What can XS cortisol cause in the kidneys?

A

cortisol stimulates Na+/K+ exchange in kidney causin hypokalemia and HTN

96
Q

what are the effects of cortisol in the liver?

A

anabolic, and increases blood glucose despite the increased glycogen storage

97
Q

Which signaling pathway is used for ACTH to activate cortisol?

A

G-protein/cAMP signaling pathway (Gsalpha), and the secretion is pulsatile

98
Q

What changes occur due to increased glucocorticoid activity?

A

Cushing’s syndrome!

  • increased glucogenesis, hepatic glycogenesis and protein catabolism
  • increased glucose, therefore increased insulin
  • reduced inflammatory response
  • increased stomach acid secretion
  • suppression of release of adrenocorticotrophin
  • Na+ retention
99
Q

What are causes of Cushing’s syndrome?

A
  • CRH producing tumor
  • ACTH producing tumor
  • Lack of feedback control by cortisol
  • Cortisol producing adrenal tumor
  • iatrogenic (greek “brought forth by a healer”) - most common cause resulting from chronic glucocorticoid therapy
100
Q

What are possible treatments of cushing’s?

A

microsurgery, various forms of radiation therapy and pharmacologic inhibition of ACTH secretion

101
Q

What characterizes Addison’s disease (hypofunction of adrenal)

A

Most commonly due to destruction of the adrenal gland by an autoimmune response
• Fatigue,weakness,faintness,nausea
• Vomiting
• Low blood pressure
• Salt craving
• Pain in muscles and joints
• Excessive freckling (release of MSH as part of opiomelanocortin)

102
Q

Tx for Addison’s disease?

A

Life long glucocorticoid and mineralcorticoid therapy

103
Q

What are the effects of aldosterone?

A
  • Main sites of action: Distal tubules and collecting ducts of the kidney. Also acts on other secretory systems (sweat glands, salivary glands, colon)
  • Promotes plasma retention of Na+ and excretion of K+ and H+ into the lumen of the tubules
  • Sensitizes arterioles to vasoconstrictor agents
  • Net effect: Rise in plasma volume and hence blood pressure
  • Response has a lag period of 1h, reflecting that aldosterone induced enzymes have to be synthesized de novo
104
Q

What is Conn’s syndrome?

A

• Hypersecretion of aldosterone usually caused by adrenal hyperplasia (60 %)
or tumor (40%)
• Excess excretion of K+ and H+
– Serum alkalosis and neuropathy (hypocalcemia)
• Increased water retention
– Increased Na reabsorption
– Increased blood pressure

105
Q

What is ANP (atrial natriuretic peptide)?

A

peptide that increases excretion of H2O and Na+, produced by heart muscle cells (cardiocytes)

106
Q

What does the zona reticularis produce?

A

Adrenal cortex (mainly zona reticularis) contributes to the production of DHEAS and androstenedione –regulated by ACTH and hypothalamic CRH. Can be converted to testosterone in peripheral tissues

107
Q

What is CAH (congenital adrenal hyperplasia)?

A

Masculinization of external genitalia at birth due to excessive androgen production, producing testosterone. 21 hydroxylase enzyme is also deficient, therefore low aldosterone (salt appetite increases, re-uptake decreases) and cortisol production (less negative feedback to hypo and pit. axis, so more steroid synthesis of androgens)

108
Q

How is CAH treated?

A

surgical correction at birth and raise as girls (tendency towards male play patterns)

109
Q

What is the rate limiting step in making nor/epinephrine?

A

Tyrosine into Dopa using the tyrosine hydroxylase enzyme (rate limiting enzyme!!!)

110
Q

What does the PNMT enzyme do and how is it regulated?

A

PNMT enzyme converts nor into epinephrine and is enhanced by cortisol. PNMT is found in tissues such as lung, kidney, and pancreas. 80% of catecholamines are epinephrine

111
Q

What enzyme inactivates epi/norepi?

A

MAO (monoamine oxidase) and COMT (catechol-O-methyltransferase)

112
Q

What do epi/norepi do in fight or flight acute response?

A
  • epi:
    rapidly mobilizes fatty acids as the primary fuel for muscle action increases muscle glycogenolysis
    mobilizes glucose for the brain by ↑ hepatic glycogenolysis/
    gluconeogenesis
    preserves glucose for CNS by ↓ insulin release leading to reduced glucose uptake by muscle/ adipose
    increases cardiac output
  • norepi: increase blood flow and lower insulin secretion
113
Q

What are the metabolic effects of catecholamines?

A
  • muscle: increased Glycogenolysis and Excretion of lactic acid
  • Liver: increased Gluconeogenesis and Glycogenolysis
  • Adipocytes: increased lipolysis
  • Low insulin, high glucagon
  • OVERALL: plasma increase in lactic acid, glucose and FAs
114
Q

What are the adrenergic receptors and what are there targets?

A

Alpha and Beta1 receptors can bind both epi/norepi, Beta2 can only bind epi. Action is through G-protein (alpha 1 =Gq, alpha 2= Gi, both betas = Gs)

  • alpha 1 (norepi>epi): smooth muscle (skin, GI)
  • alpha 1 (epi>norepi): nerve terminals (synaptic transmission)
  • beta1 (norepi>epi): heart, cerebral cortex
  • beta2 (epi>norepi): lung, smooth muscle, crebellum
115
Q

What are the differences between norepi and epi?

A
  • Epinephrine&raquo_space; norepinephrine – in terms of cardiac stimulation leading to greater cardiac output (β stimulation).
  • Epinephrine < norepinephrine – in terms of constriction of blood vessels – leading to increased peripheral resistance – increased arterial pressure.
  • Epinephrine&raquo_space; norepinephrine –in terms of increasing metabolism
116
Q

What are adrenomedullary disorders?

A
  • Adrenomedullary deficiency: can occur due to surgery, trauma etc.
  • Also if cortisol levels are suppressed for any reason (high concentration of cortisol req’d for transcription of PNMT) resulting in epinephrine deficiency
  • Hypotension, Hypoglycemia (but central nervous system and glucocorticoids are more important, respectively)
  • Adrenal catecholamines not essential for life
117
Q

What is pheochromocytoma?

A

tumour overproducing catecholamines. the usual symptoms are headache, HTN, sweating. it can be surgically removed.

118
Q

What is an autoimmune disease?

A

When the body produces antibodies and cytotoxic T cells that target normal body cells. it occurs mostly in older individuals and more in women than men

119
Q

What are examples of autoimmune diseases?

A

Grave’s disease, T1DM, pernicious anemia, rheumatoid arthritis, Hashimoto’s disease and vitiligo (depigmentation of skin)

120
Q

What is the link between estrogens and autoimmunity?

A

Estrogens stimulate B cell autoimmunity such as MS, SLE, coeiliac disease, etc.
Falling estrogens support T cell autoimmunity, such as rheumatoid arthritis, primary biliary cirrhosis, Sjogren syndrome.

121
Q

What happens when immunologically privileged sites are injured?

A

It can lead to autoimmunity: brain, eye, testis, uterus (Fetus), hamster cheek pouch

122
Q

Where do hemapoietic stem cells come from?

A

bone marrow

123
Q

Where do the osteoclast and osteoblast originate from?

A

Osteoclast: hematopoietic stem cells (myeloid progenitor)
Osteoblast: mesenchymal stem cells (multipotent progenitor)

124
Q

Where do T-cells mature once produced in the bone marrow?

A

In the thymus!

125
Q

What is the difference between antibody mediated immunity and cell mediated immunity?

A
  • Antibody mediated immunity: T cells recognize non-self antigen, recruit B cells to produce antibodies, these bind to nonself antigens and mature to destroy infected cells
  • Cell mediated immunity: Macrophages phagocytize pathogens, present non self antigens on membrane, helper T cells recognize non self antigens and recruit cytotoxic T cell, which destroy infected cells
126
Q

How are self-reactive lymphocytes eliminated or inactivated to prevent autoimmunity?

A

By immunological tolerance! specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
(implies antigen specificity, in contrast to “non-specific immunosuppression”)
- breakdown of self-tolerance results in autoimmunity
- Therapeutic potential: inducing tolerance can help prevent graft rejection, treat autoimmune and allergic diseases, prevent immune responses in gene therapy, and maybe stem cell transplantation

127
Q

What is central tolerance?

A

immature self-reactive lymphocytes that recognize self antigens in generative (central) lymphoid organs die by apoptosis; other fates

128
Q

What is peripheral tolerance?

A

Mature self-reactive lymphocytes that recognize self antigens in peripheral tissues are inactivated (anergy), killed (deletion) or suppressed

129
Q

Describe tolerance.

A

Generation of immune repertoires, maturation in bone marrow (B cells) and thymus (T cells).

  • Central tolerance = self-reactive lymphocytes are deleted by negative selection
  • Peripheral tolerance = leakage of self-reactive lymphocytes controlled
  • If tolerance fails, either bc of wrong environment (viral infection) or wrong genes or mutations, causing an autoimmune disease.
130
Q

What are the factors that could cause failure of central or peripheral self-tolerance?

A

genetics,environmental, diet, aging, stress, pregnancy, trauma, disease, etc.

131
Q

What are the antibodies present in T1DM?

A

Usually antibodies against glutamic acid decarboxylase (GAD65) and IA-2 (a tyrosine phosphatase) – about 90 % of individuals (also anti-insulin Ig in about 50 % of individuals)

132
Q

What are the antibodies present in thyroid autoimmune disease (grave’s disease)?

A

anti-TSHR, TPO

133
Q

What are the antibodies present in thyroid autoimmune disease (hashimoto’s disease)?

A

anti-TPO, Tg

134
Q

What are the antibodies present in adrenal autoimmune disease (addison’s disease)?

A

mainly anti 21-hydroxylase (enzyme involved in steroid hormone synthesis)

135
Q

True or false: rheumatoid arthritis is 3 times more common in women than men and is susceptibly a partially genetic cause.

A

TRUE

136
Q

What can be caused by inflammation due to rheumatoid arthritis?

A

Bone erosion by activating osteoclasts.

137
Q

What are some prevalent autoimmune diseases and their targets?

A
  • IDDM: islet beta cells of the pancreas
  • MS: myelin producing cells in the CNS
  • Rheumatoid arthritis: collagen producing cells of the joints
138
Q

What is the evidence about vitamin D3 and immunosuppression?

A

Reduced incidence of autoimmune diseases in areas of increased sunshine and/or diet rich in vitamin D3. Intervention studies in animal models of autoimmunity

Metabolic Endocrinology (3 decks)

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