Endocrine Day 4- Thyroid and Pancreas Flashcards Preview

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Flashcards in Endocrine Day 4- Thyroid and Pancreas Deck (56)
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1

Hormones involved in thyroid HPA axis

  • TRH- released from anterior hypothalamic area
  • TSH released from thyrotrophs in anterior pituitary
  • TH released from thyroid
    • T4- 10x more secreted then T3
    • T3- less secreted, more potent
  • SOmatostatin can inhibit thyrotrophs as well

2

TSH is similar in structure to which hormones?

  • LH
  • FSH
  • HCG

All have same alpha subunit

3

What is the functional unit of the thyroid gland? How does it appear with activation of TSH and unstimulated?

Follicle

  • Without activation of TSH, T3/t4 thyroglobulin matrix is stored inside colloid
  • With activation of TSH, invaginations appear on colloid membrane to reabsorb T3/T4

4

What is the biosynthesis of T3/T4?

  • Tyrosine (AA) converts to monoidotyrosine or diiodotyrosin in the presence of iodinase
  • Monoido and di iodo can combine to make T3
  • 2 diiodotyrosine can combine to make T4

5

What causes T3/T4 to be synthesized inside thyroid cell?

  • Binding of TSH causes activation of Na-I transport (secondary active transport) (Na/K ATPase dependent)
    • this brings iodide into cell
  • Organification of Iodide via peroxidases inside cell
  • "Coupling" of MIT and DIT to itself makes T3/T4
  • Attaches to thyroglobulin backbone (all stored together in colloid)

6

What occurs to cause secretion of T3/T4?

  • With continued TSH production, apical membrane of thyroid cell develops invaginations to pinch off colloid and bring it into cell
  • Inside cell, lysosomes have proteolytic and hydrolytic enzymes
    • liberates MIT, DIT, T3, T4 from thyroglobulin
  • T3/T4 aromatase ring allows it to freely leave plasma membrane into blood
  • MIT, DIT stays inside thyroid cell to be reused

7

TSH acts to increase ___ inside cell

cAMP

  • important to remember because cAMP can be stimulated by other things and this will also increase thyroid hormone production

8

What are 2 major end effects of TSH on the cell?

  • Stimulates thyroid gland hormone production
  • increases thyroid cell size and cellular proliferation by increase cAMP levels

9

When T4 binds to cell, it is converted to ____ by _____.

T3; 5'-deiodinase

10

What actions does T3 have once inside target cell? (at normal physiologic levels)

  • Stimulates Na-K ATPase
  • Increases mitochondria and respiratory enzymes
  • increases other enzymes, proteins such as growth hormone
  • proteins for growth and maturation

At normal physiologic levels, TH is anabolic

11

What whole body effects does high level of TH have on body?

At high physiologic levels, TH is catabolic

  • increased O2 consumption causes
    • increased CO
    • Increased ventilation
  • Increased upatke of substrates
    • increase food uptake
    • increased mobilization of endogenous carbs, protein, fat
  • Increased metabolic rate
    • increase CO2, heat
    • increase urea
    • decrease muscle mass
    • decrease adipose tissue
    • increase thermogenesis
    • increase sweating
    • increase insensible loss

 

12

What whole body effects does TH have on metabolic rate?

  • Increase CO2, increase urea, 
  • increase muscle mass
  • decrease adipose tissue
  •  

13

How is TSH production affected in cold environment?

Stimulated

Increase in TH then maintains body temperature

14

What is TSH production in warm environment?

  • Inhibit TRH-TSH-TH levels

15

What are TSH levels like in hypothyroidism?

Very high due to lack of negative feedback from TH

16

What are TSH levels like in hyperthyroidism?

Very low due to increased negative feedback from thyroid hormone

17

What are TSH levels like in hypopituitarism?

  • Very low d/t inability to make TSH

18

What happens when you inject TRH into patient with hypothyroidism?

HUGE increase in TSH 

  • With loss of TH, TRH receptors are upregulated on thyrotrophs
  • so, when TRH injected, get exaggerated release of TSH

19

What happens when you inject TRH into hyperthyroid patient?

No change in TSH production

  • With increase TH production, get downregulation of receptors, so no response from injected TRH

20

What is grave's disease?

  • Autoimmune diseaes caused by production of autoantibody called thyroid stimulating immunoglobulin
    • antibody binds to TSH receptor, elevates cAMP and stimulates excess TH production
  • Symptoms
    • exophthalmus
    • rasies BMR
    • accerlerates organ activity
    • increases beta adrenergic receptors on CV tissue
      • more sensitive to catecholamines
    • hyperphagia
    • increase body temp
    • smooth, velvety skin

21

What is goiter?

  • Increased proliferation of thyroid cells d/t excessive TSH secretion from lack of TH
  • Occurs with iodine deficiency, no iodine to make TH 

22

What is cretinism? (congenital hypothyroidism)

  • Arises from perinatal deficiency of thyroid hormone
  • lack of TH results in slowing of mentation d/t failure of
    • dendritic branching of neurons
    • reduction in synapses
    • reduced myeline formation
  • Avoided by admin of TH to newborn if TH found to be low

23

What is Myxedema?

  • Adult hypothyroidism
  • lacks TH, results in accumulation of mucopolysaccharides
    • causes osmotic effect and edematous appearance
  • leads to incrase fat accumulation and impair wound healing
  • slow metabolism, constipation, cold intolerance and dry skin

24

Why is KI given before thyroid surgery?

  • decreases proliferation of TH
  • May cause less of a problem at surgery if pt is pretrated with KI

25

What is thyroid storm?

  • d/t increased TH, increased beta adrenergic receptors, when hyperthyroid patient goes into surgery, they can release a lot of catecholamines
  • with extra beta adrenergic receptors, this can result in VF, MI
  • To prevent thyroid storm, can give KI preop or treat HR during sx with propranolol

26

What is the Wolf-Chaikoff effect?

decrease in TH caused by excess iodine admin with KI

27

What do beta cells in pancreas secrete?

insulin

28

What do alpha cells in pancreas secrete?

Glucagon

29

What do delta cells in pancreas secrete?

Somatostatin

30

All hormones inside pancreas exhibit ____ response

paracrine

31

What does increase insulin cause?

  • Decrease in glucagon
  • stores substrate 

32

What does increase glucagon cause?

  • increases insulin
  • increases substrate in blood

33

Somatostatin is the ____

seesaw

  • has ability to inhibit both glucagon, insulin to a balance

34

In order to make sure SS doesn't get out of control, it has its own ____ action

autocrine

35

Glucagon also _____ somatostatin

stimulates

36

What kind of molecule is insulin?

  • Human Proinsulin molecule manufactured by beta cell
  • Has A, B, chain and C peptide
  • not active until c peptide cleaved then mature insulin is created and can be secreted from beta cells
    • pro-insulin and intermediate processing molecuels have little biologic activity
  • 51 AA molecule secreted into blood from beta cells has 100% activity at insulin receptor
  • C peptide made in equimolar quantities as inuslin
    • no biologic effect on own
    • can be used to evaluate endogenous insulin production

37

What effect does insulin have on cell?

  • Insulin stimulates processes that result in uptake or influx of certain solutes
    • especially glucose, FFA, K, PO4
  • causes series of autophosphorylation of enzymes
  • Stimulates
    • glycogen synthase (glucose--> glycogen)
    • pyruvate dehydrogenase
    • protein synthesis
  • Inhibits
    • lipolysis (wants to store FFA as fats, so will inhibit breakdown of fats)
    • protein degradation (Because you want to store protein)
    • gluconeogenesis (because you want to store glucose)

38

How is glucose moved into cell upon binding of insulin?

  • Binding of insulin stimulates translocation of glucose transporter molecules stored inside cell
  • glucose transporters inserted on plasma membrane
    • FD brings glucose into cell
  • THese are called GLUT transproters. different GLUT transporters found on different membrane

39

What happens to glucose transporters once insulin removed?

Glucose transporters removed from plasma membrane and stored in cell.

40

What happens to insulin/glucagon levels with exogenous fuels? What are the outcomes?

  • Exogenous fuels such as flucose, FFA, stimualte insulin secretion by beta cell signaling
  • also inhibits glucagon secretion
    • when insulin high, directly inhibits glucagon by alpha cells
  • Causes
    • increase in glycogenesis
    • increase lipogenesis
    • increase protein biosynthesis

41

What happens to insulin and glucagon when no exogenous fuels present? What does this cause?

  • Increase in glucagon (alpha), decrease in insulin
    • further increase in glucagon because there is no insulin to inhibit it
  • Causes
    • increase in glucogenolysis
    • increase lipolysis
    • increase ketogenesis
    • increase gluconeogenesis
  • Creates endogenous fuel production

42

What's the difference in insulin/glucagon/glucose levels in carb vs protein meal?

  • Carb meal
    • glucose increase in blood stream as it's processed through GI tract
    • glucose causes robust increase in insulin level
    • driving force to decrease glucagon rapidly, is insulin
    • SO overall, spike in insulin, rapid decrease glucagon, quick plateau in glucose caused by slope down (by action of insulin) (chart on right)
  • Protein meal (left chart)
    • Nitrogenous compounds increase after protein intake
    • AA can stimulate beta cell release of insulin, but it is not as robust as glucose
    • Insulin doesn't restrain glucagon, so glucagon levels are going up
      • insulin then rises, causing AA to be taken up by target tissue
    • Eventually raise glucose levels, but more steps in process

43

What do cellular processes looking like in resting state?

  • Glucagon and insulin are in balance
  • Insulin stimulates uptake of substrates by liver, muscle fat
    • insulin is not needed for uptake of glucose into brain
  • As insulin is placing glucose into cell, need to replace glucose in blood stream SO
    • glucagon acts on liver to liberate glucose from glycogen stores

44

What happens in cells in fight or flight response (in relation to insulin/glucagon)

  • stres activates sympathetic inputs to pancreas
  • In fight or flight response, increase glucagon causes release of glycogen stores from the liver (glycogenolysis)
    • push more substrates into bloodstream for use
  • Inhibit insulin
    • working muscle does not require insulin for glucose uptake
      • physical movement of myosin/actin moves glucose transporters to cell of membrane of muscle cells

45

What is effect on glucagon and insulin during famine?

  • If no substrate consumed, absence of substrate leads to inhibiton of insulin
  • Inhibiton of insulin removes restraint on glucagon
  • Glucagon stimulated
    • increase release of glycogen from liver
      • stores run out in 4-6 hours
    • then increase alternate substrate called ketones made from FFA from fat stores 
    • brain and fat cells can use ketones as energy source
  • metabolic acidosis from excess ketone produciton, however, can lead to failure of CNS

46

What is the anticipatory rise of insulin?

  • Rise in insulin due to presence of food and food substrate in GI tract, even before substrate arrives in circulation
  • incrase PSNSN to pancreas d/t feeding and stimulation also increases insulin secretion
  • promotes quick arrival of substrate into blood stream

47

What is type I diabetes?

  • Complete absence of insulin d/t destruction of beta cells
    • usually occurs because of virus 
      • virus has coating like beta cells, immune system makes response to clear virus, and also kills beta cells in process
  • Glucagon goes WAY up, nothing to provide negative feedback
  • Increase in glycogenolysis, gluconeogenesis, increasing glucose into circulation
    • BUT can't take up glucose into muscle cells in absence of insulin
  • Glucose builds up in circulation, can be released by kidneys in urine
  • eventually, renal cells will become damaged by excess glucose

48

What is type 2 diabetes?

insulin resistance by high levels of insulin downregulating receptors from desensitization

49

What 3 things does insufficient insulin cause?

  • Increase lipolysis
  • decrase glucose utilization
  • increase protein catabolism

50

What does decrease in glucose utilization cause?

  • decrease lipogenesis 
  • decrease protein anabolism

51

What are ketons formed from?

FFA from increased lipolysis, causing ketonemia, and eventually ketonuria

52

What does hyperglycemia cause in the body?

  • Glucosuria
  • osmotic diuresis
  • loss of H2O, Na, K, Cl, PO4
  • Hypovolemia
  • decrease CO
  • Hypotension
  • Decrease renal blood flow
  • decrease renal function
    • this further worsens metabolic acidosis because body can't excrete excess H ions d/t poor kidney function

53

What does increase in protein catabolism and decrease in protein anabolism cause?

  • Increase in AA
    • increase in BUN
  • Increase in kalemia
  • increase in phosphatemia

54

What is eventual end result in untreated DKA?

Neuronal dehydration causing death

55

Do you see ketosis in Type II diabetics?

Not typically

  • Enough insulin to restrain glucagon output from pancreas
  • doesn't drive pathway of ketogenesis
  • usually suffer form neuronal dehydraiton

56

What happens to cells with ongoing hyperglycemia?

  • Glycosylation of cells
  • creates HbA1c- glycosylation of HGB
    • impairs ability to release O2 to tissue, causing tissue to be anoxic
  • glycosylation of neurons causes neuropathies
  • impairs flexibility of RBC
    • can't fit thourhg capillaries and contribute to perfusion