Pbl Exam 1 Case 3

Front 1

1. Psychosexual (definition)

Back 1

Term used to describe personality development and function as these are affected by sexuality.

Applies to more than sexual feelings and behavior and is NOT synonymous with libido

Front 2

2. Sexuality depends of what four interrelated psychosexual factors?

Back 2

1. Sexual identity
2. Gender identity
3. Sexual orientation
4. Sexual behavior

Front 3

3. Sexual identity and gender identity (definition)

Back 3

Sexual identity is the pattern of a person's biological sexual characteristics: chromosomes, external and internal genitalia, hormonal composition, gonads, and secondary sex characteristics

Gender identity is a person's sense of maleness or femaleness.

Sexual identity and gender identity are interactive.

Front 4

4. When does differentiation of the male from the female take place?

What occurs then?

Back 4

About the sixth week of embryonic life and is completed around the end of the third month.

Results from the action of fetal androgens

Front 5

5. Important genes development

Back 5

Testes develop as a results of the Y chromosome which codes for the SRY gene.

SRY
SOX9
DAX1 - plays a part in both sexes
WNT4 - needed for Mullerian ducts

Front 6

6. By what age do most people have a firm gender identity?

Back 6

By 2 to 3 years

Yet, even if maleness and femaleness develop normally, persons must still develop a sense of masculinity or femininity.

Front 7

7. Where does the formation of gender identity come from?

Back 7

The formation of gender identity arises from parental and cultural attitudes, the infant's external genitalia, and a genetic influence, which is physiologically active by the sixth week of fetal life

Front 8

8. Virilizing adrenal hyperplasia (adrenogenital syndrome)

Back 8

Results from excess androgens in fetus with XX genotype

Most common female intersex disorder

Associated w/enlarged clitoris, fused labia, hirsutism in adolescence

Front 9

9. Turner's syndrome

Back 9

Results form absence of second female sex chromosome XO

Associated w/webbed neck, dwarfism, cubitus valgus, no sex hormones produces, and infertility

Front 10

10. Klinefelter's syndrome

Back 10

Genotype is XXY

Male habitus present w/small penis and rudimentary testes b/c of low androgen production

Weak libido; usually assigned as male.

Front 11

11. Androgen insensitivity syndrome

Back 11

Congenital X-linked recessive disorder that results in inability of tissues to respond to androgens.

External genitals look female and crytorchid testes present.

In extreme form the patient has breasts, normal external genitals, short blind vagina and absence of pubic and axillary hair.

Front 12

12. Enzymatic defects in XY genotype

5-α--reductase deficiency

17-hydroxy-steroid deficiency

Back 12

Congenital interruption in production of testosterone that produces ambiguous genitals and female habitus

Front 13

13. True hermaphroditism

Back 13

True hermaphrodite is rare and characterized by both testes and ovaries in same person (may be 46 XX or 46 XY)

Front 14

14. Pseudohermpahroditism

Back 14

Usually the result of endocrine or enzymatic defect (CAH) in persons with normal chromosomes

Female pseudohermaphrodites have masculine looking genitals but are XX

Male pseudohermaphrodites have rudimentary testes and external genitalia and are XY

Front 15

15. Things needed to establish gender role

Back 15

The major factor in achieving the role appropriate to a person's sex is learning.

1. Experiences encountered
2. Explicit instruction
3. Spontaneously putting 2 and 2 together to make 4 and sometimes 5
4. Congruence of gender identity and gender role

Front 16

16. Can a person's gender role be opposed to their gender identity?

Back 16

Yes, they may identify w/their own sex and yet adopt the dress, hairstyle or other characteristics of the opposite sex.

Or, they may identify with the opposite sex and yet for expediency adopt many behavioral characteristics of their own sex.

Front 17

17. Role of the cortex in sexual behavior

Back 17

Involved in both controlling sexual impulses and in processing sexual stimuli that may lead to sexual activity

Front 18

18. Orbitofrontal cortex

Back 18

Involved in emotions

Front 19

19. Left anterior cingulate cortex

Back 19

Involved in hormone control and sexual arousal

Front 20

20. Right caudate nucleus

Back 20

Activity is a factor in where sexual activity follows arousal

Front 21

21. Role of limbic system in sexual behavior

Back 21

Directly involved w/elements of sexual functioning.

Chemical or electrical stimulation of the lower part of the septum and the contiguous preoptic area, the fimbria of the hippocampus, the mammilary bodies, and the anterior thalamic nuclei have all elicited penile erections..

Front 22

22. Role of brainstem in sexual behavior

Back 22

Exerts inhibitory and excitatory control over spinal sexual reflexes.

The nucleus paragigantocellularis projects directly to pelvic efferent neurons, apparently causing them to secrete serotonin, which is known to inhibit orgasm.

Front 23

23. Roles of brain neurotransmitters in sexual behavior

Back 23

Dopamine increases libido

Serotonin, produced in the upper pons and midbrain, exerts an inhibitory effect on sexual function

Oxytocin is released w/orgasm and is believe to reinforce pleasurable activities

Front 24

24. Role of the spinal cord in sexual behavior

Back 24

Sexual arousal and climax are organized at the spinal level.

Sensory stimuli related to sexual functions are conveyed via afferents from the pudendal, pelvic, and hypogastric nerves.

Proposed that sexual reflexes are mediated by spinal neurons in the central gray region of the lumbosacral segments.

Front 25

25. What are the four phases of the sexual response cycle according to the DSM?

Back 25

1. Desire
2. Excitement
3. Orgasm
4. Resolution

*It is important to remember that the sequence of responses can overlap and fluctuate.

Front 26

26. Orgasm similarities and differences in males and females

Back 26

The male orgasm is also associated with four to five rhythmic spasms of the prostate, seminal vesicles, vas, and urethra.

In women, orgasm is characterized by 3 to 15 involuntary contractions of the lower third of the vagina and by strong sustained contractions of the uterus, flowing from the fundus downward to the cervix.

Both men and women have involuntary contractions of the internal and external anal sphincters. These and the other contractions during orgasm occur at 0.8-second intervals.

Front 27

27. Did Freud consider homosexuality a mental illness?

Back 27

No, he wrote that homosexuality is found in persons who exhibit no other serious deviations from normal whose efficiency is unimpaired and who are indeed distinguished by especially high intellectual development and ethical culture

Front 28

28. Circulatory androgens in gay men vs. heterosexual men

Back 28

Gay men exhibit lower levels of circulatory androgens than do heterosexual men

Front 29

29. Hyperadrenocorticalism

Back 29

Women with hyperadrenocorticalism are lesbian and bisexual in greater proportion than women in the general population.

Front 30

30. Genetic differences between gays and straights

Back 30

Genetic studies have shown a higher incidence of homosexual concordance among monozygotic twins than among dizygotic twins; these results suggest a genetic predisposition, but chromosome studies have been unable to differentiate homosexuals from heterosexuals.

Front 31

31. Ego-dystonic sexual orientation

Back 31

Occurs when the gender identity or sexual preference is not in doubt but the individual wishes it were different b/c of associated psychological and behavioral disorders and may seek treatment in order to change it.

Front 32

32. Endocrine hormones

Back 32

released by glands or specialized cells into the circulating blood and influence the function of cells at another location in the body.

Front 33

33. Neuroendocrine hormones

Back 33

Secreted by neurons into the circulating blood and influence the function of cells at another location of the body

Front 34

34. Paracrines

Back 34

Secreted by cells into the extracellular fluid and affect neighboring cells of a different type

Front 35

35. Autocrines

Back 35

Secreted by cells into the extracellular fluid and affect the function of the same cells that produced them by binding to cell surface receptors

Front 36

36. Cytokines

Back 36

Peptides secreted by cells into the extracellular fluid and can function as autocrines, paracrines, or endocrine hormones.

Include interleukins and lymphokines that are secreted by helper cells and act on other cells of the immune system.

Front 37

37. Three classes of hormones

Back 37

1. Proteins and polypeptides
2. Steroids
3. Derivatives of the amino acid tyrosine

Front 38

38. Where are polypeptide and protein hormones synthesized?

Where are they stored?

Back 38

Synthesized on the rER into preprohormones and then cleaved into prohormones in the ER. Then, they are transferred to the Golgi for packaging.

Enzymes in the vesicles cleave the prohormones to produce smaller, biologically active hormones.

They are then stored in secretory vesicles until needed.

Front 39

39. Polypeptides

Back 39

Those with 100 or more amino acids are called proteins

Those with fewer than 100 are called peptides

Front 40

40. Secretion of hormones

Back 40

Occurs following the depolarization of the plasma membrane; the secretory vesicles fuse w/the cell membrane and the granular contents are extruded into the interstitial fluid or blood via exocytosis.

Front 41

41. Are peptide hormones water soluble?

Back 41

Yes, allowing them to enter the circulatory system easily to reach their target tissues.

Front 42

42. Synthesis and storage of steroid hormones

Back 42

Usually synthesized from cholesterol and are not stored. They are lipid soluble and consist of three cyclohexyl rings and one cyclopentyl ring combined into a single structure

Once they are synthesized, they simply diffuse across the cell membrane and enter the interstitial fluid and then the blood

Front 43

43. What are the two groups of hormones derived from tyrosine?

Back 43

1. Thyroid hormones

2. Adrenal medullary hormones

Front 44

44. Where are amine hormones derived from?

Back 44

Derived from tyrosine; formed by the actions of enzymes in the cytoplasmic compartments of the glandular cells.

Front 45

45. Thyroid hormones

Back 45

Synthesized and stored in the thyroid gland and incorporated into macromolecules of the protein thyroglobulin, which is stored in large follicles within the thyroid.

Hormone secretion occurs when the amines are split from thyroglobulin and the free hormones are then released into the blood stream.

After entering the blood, they combine with plasma proteins, esp thyroxine-binding globulin, which slowly releases the hormones to the target tissues.

Front 46

45. Epinephrine and norepinephrine

Back 46

Catecholamines:
Formed in the adrenal medulla, which normally secretes about 4x more epinephrine than norepinephrine.

Taken up into preformed vesicles and stored until secreted. Also released from adrenal medullary cells by exocytosis.

Front 47

46. Control variable in negative feedback of hormone systems

Back 47

It is not the secretory rate of the hormone itself, but rather the degree of activity of the target tissue.

Front 48

47. Example of positive feedback in hormones

Back 48

Luteinizing hormone:

Surge of LH occurs as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation.

The secreted LH then acts on the ovaires to stimulate additional release of estrogen, which causes more LH to be screted.

Front 49

48. Cyclical variations of hormone release

and example?

Back 49

Periodic variations of hormone secretion that are influenced by seasonal changes, various stages of development and aging, the diurnal cycle, and sleep.

Secretion of growth hormone is markedly increased during the early period of sleep but is reduced during the later stages of sleep.

Front 50

49. Binding of hormones to plasma proteins

Back 50

Plasma bound hormones cannot easily diffuse across the capillaries and gain access to their target cells and are therefore biologically inactive until they dissociate from the plasma proteins.

Being bound also slows their clearance from the plasma

Front 51

50. Two factors that can increase or decrease the concentration of a hormone in the blood

Back 51

1. Rate of hormone secretion into the blood

2. Rate of removal of the hormone from the blood (metabolic clearance rate)

Front 52

51. Metabolic clearance rate

Back 52

Depends on:

D. the rate of disappearance of the hormone from the plasma per min

C. the concentration of the hormone in each mL of plasma.

MCR = D/C

Front 53

52. How are hormones cleared from the plasma?

Back 53

1. metabolic destruction by the tissues
2. binding with the tissues
3. excretion by the liver into the bile
4. excretion by the kidneys into the urine

Front 54

53. Location for the different types of hormone receptors are where?

Back 54

1. In or on the surface of the cell membrane
-mostly for the protein, peptide, and catecholamine hormone receptors

2. In the cell cytoplasm
-primarily for steroid hormone receptors

3. In the cell nucleus
-receptors for the thyroid hormones are found here

Front 55

54. Down regulation of hormone receptors

Back 55

Increased hormone concentration and increased binding w/its target cell receptors sometimes cause the number of active receptors to decrease

Front 56

55. When does this down regulation occur?

Back 56

1. inactivation of some of the receptor molecules
2. inactivation of some of the intracellular protein signaling molecules
3. temporary sequestration of the receptor to the inside of the cell away from the hormones
4. destruction of the receptors by lysosomes after they are internalized
5. decreased production of the receptors

Front 57

56. Up regulation of hormone receptors

Back 57

The stimulating hormone induces greater than normal formation of receptors or intracellular signaling molecules by the protein manufacturing machinery of the cell, or greater availability of the receptor for interaction w/the hormone.

Front 58

57. Ion channel-linked receptors

Back 58

When hormones bind with the receptors (usually neurotransmitters), they almost always cause a change in the structure of the receptor, usually opening or closing a channel for one or more ions.

Most hormones open or close these ion channels indirectly by coupling with G protein-linked or enzyme-linked receptors.

Front 59

58. Protein-linked receptors

Back 59

Many hormones activate receptors that indirectly regulate the activity of target proteins by coupling w/groups of cell proteins called heterotrimeric GTP-binding proteins (G-proteins)

Front 60

59. G-proteins

Back 60

There are over 1000 known G proteins, all of which have 7 transmembrane segments that loop in and out of the cell membrane.

The three trimeric parts are alpha, beta, and gamma subunits.

Front 61

60. Hormone action on G-proteins

Back 61

When the hormone binds to the G-protein, it causes a conformational change that causes the GDP-bound trimeric G-protein to associate w/the cytoplasmic part of the receptor and to exchange GDP for GTP.

Front 62

61. Significance of the exchange of GDP for GTP.

Back 62

This exchange causes the alpha subunit to dissociate from the trimeric complex and to associate with other intracellular signaling proteins, which, in turn alter the activity of ion channels or intracellular enzymes

Front 63

62. How does the G-protein deactivate itself?

Back 63

The signaling event is rapidly terminated when the hormone is removed and the alpha subunit inactivates itself by converting its bound GTP to GDP

Next, the alpha subunit once again combines w/the beta and gamma subunits to form the inactive G-protein

Front 64

63. Inhibitory and stimulatory G proteins

Back 64

Some hormones couple to inhibitory or stimulatory G proteins.

Thus, depending on which they couple to, a hormone can either increase or decrease the activity of intracellular enzymes.

Front 65

64. Enzyme-linked hormone receptors

Back 65

Some receptors when activated function directly as enzymes or are closely associate w/enzymes that they activate.

*They are proteins that pass thru the membrane only once.

They have a hormone binding site on the outside of the cell and their catalytic or enzyme binding site is on the inside.

Front 66

65. Example of an enzyme-lined receptor

Back 66

The leptin receptor; leptin is a hormone secreted by fat cells and has many physiological effects.

Binding of leptin to the extracellular part of the receptor alters its conformation and enables phosphorylation and activation of the intracellular associated JAK2 molecules.

These JAK2 molecules then phosphorylate other tyrosine residues within the leptin receptor.

Front 67

66. Catalytic formation of cAMP

Back 67

Another example of an enzyme-linked receptor; when the hormone binds with a special transmembrane receptor which then becomes the activated enzyme adenyl cyclase at the end that protrudes to the interior of the cell.

This cyclase catalyzes the formation of cAMP.

Front 68

67. Intracellular hormone receptors

Back 68

Steroid hormones bind w/protein receptors on the inside of the cell b/c they are lipid soluble and can easily cross the cell membrane.

The activated hormone-receptor complex then binds w/a specific regulatory promoter sequence of the DNA called the "hormone response element" which either activates or represses gene transcription

Front 69

68. Three important second messengers used by hormones

Back 69

1. cAMP
2. Calcium ions associated w/calmodulin
3. Products of membrane phospholipid breakdown

Front 70

69. Release of cAMP

Back 70

Formed by stimulatory G-proteins on the inside of the cell and usually activates a cascade of enzymes.

The importance of this mechanism is that only a few mols of activated cAMP immediately inside the cell membrane can cause many more mols of the next enzyme to be activated, and so on.

Front 71

70. Reduction of cAMP formation

Back 71

If the hormone receptor is coupled to an inhibitory G-protein, then adenyl cyclase will be inhibited, reducing the formation of cAMP.

Front 72

71. Action of cAMP in target cells

Back 72

Depends on the nature o the intracellular machinery.

Thus, a thyroid cell stimulated by cAMP forms thyroxine and T3, wheres the same cAMP in an adrenocortical cell causes secretion of the adrenocortical steroid hormones.

Front 73

72. Cell membrane phospholipid second messenger system

Back 73

Some hormones activate transmembrane receptors that activate the enzyme phospholipase C.

This enzyme catalyzes the breakdown of some phospholipids in the cell membrane, which mobilizes calcium ions from mitochondria and ER and the calcium ions then have their own second messenger effects.

Front 74

73. Arachidonic acid

Back 74

Precursor for the prostaglandins and other local hormones.

Front 75

74. Calcium-calmodulin second messenger system

Back 75

When Ca enters a cell, the ions bind w/the protein calmodulin.

This protein has four Ca sites, and when 3 or 4 of these sites have bound w/Ca, the calmodulin changes its shape and activates or inhibits protein kinases

Front 76

75. Activation of calmodulin-dependent protein kinases

Back 76

Causes phosphorylation, activation or inhibition of proteins involved in the cells response to the hormone.

Front 77

76. Similarity of calmodulin system and skeletal muscle

Back 77

The calcium ion concentration needed to activate calmodulin is almost the same amount needed to activate troponin-C in skeleton muscle contraction

Front 78

77. Synthesis of proteins on target cells

Why is there a minimum 45 min delay for the full action of steroid hormones?

Back 78

1. The steroid hormone diffuses across the cell where it binds to the receptor protein
2. The combined receptor protein-hormone then diffuses into or is transported into the nucleus
3. The combination binds at specific points on the DNA strands in the chromosomes, which activates the transcription of mRNA
4. The mRNA diffuses into the cytoplasm where it promotes the translation process at the ribosomes to form new proteins

Front 79

78. Type important features of thyroid hormones

Back 79

1. They activate the genetic mechanisms for the formation of many types of intracellular proteins

2. Once bound to the intranuclear receptors, the thyroid hormones can continue to express their control functions for days or even weeks

Front 80

79. Radioimmunoassay 1

Back 80

A scientific method used to test antigens (for example, hormone levels in the blood)

To perform a radioimmunoassay, a known quantity of an antigen is made radioactive, frequently by labeling it with gamma-radioactive isotopes of iodine attached to tyrosine. This radiolabeled antigen is then mixed with a known amount of antibody for that antigen, and as a result, the two chemically bind to one another. Then, a sample of serum from a patient containing an unknown quantity of that same antigen is added. This causes the unlabeled (or "cold") antigen from the serum to compete with the radiolabeled antigen for antibody binding sites.

Front 81

80. Radioimmunoassay 2

Back 81

As the concentration of "cold" antigen is increased, more of it binds to the antibody, displacing the radiolabeled variant, and reducing the ratio of antibody-bound radiolabeled antigen to free radiolabeled antigen.

The bound antigens are then separated from the unbound ones, and the radioactivity of the free antigen remaining in the supernatant is measured.

A binding curve can then be plotted, and the exact amount of antigen in the patient's serum can be determined.

Front 82

81. ELISA

Back 82

Enzyme-linked immunosorbent assay
is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample.

In simple terms, in ELISA an unknown amount of antigen is affixed to a surface, and then a specific antibody is washed over the surface so that it can bind to the antigen. This antibody is linked to an enzyme, and in the final step a substance is added that the enzyme can convert to some detectable signal. Thus in the case of fluorescence ELISA, when light of the appropriate wavelength is shone upon the sample, any antigen/antibody complexes will fluoresce so that the amount of antigen in the sample can be inferred through the magnitude of the fluorescence.

Front 83

82. Why is the ELISA method widely used?

Back 83

1. It does not employ radioactive isotopes

2. Much of the assay can be automated using 96-well plates

3. It has proved to be a cost-effective and accurate method for assessing hormone levels.

Front 84

83. Composition of the adrenal glands

Back 84

1. Adrenal medulla
-secretes epinephrine and norepinephrine

2. Adrenal cortex
-secretes corticosteroids

Front 85

84. Mineralcorticoids

Back 85

They specially affect the electrolytes (the "minerals") of the extracellular fluids; sodium and potassium, in particular.

Aldosterone: principal mineralcorticoid

Front 86

85. Glucocorticoids

Back 86

They exhibit important effects that increase blood glucose concentration.

They have additional effects on both protein and fat metabolism that are equally as important to body function as their effects on carbohydrate metabolism.

Cortisol: principal glucocorticoid

Front 87

86. Three layers of the adrenal cortex

Back 87

1. zona glomerulosa
2. zona fasciculata
3. zona reticularis

Front 88

87. Zona glomerulosa

Back 88

Outer layer:
Only layer with cells capable of secreting significant amts of aldosterone b/c they contain the enzyme aldosterone synthase.

Secretion is controlled by angiotensin II and potassium.

Front 89

88. Zona fasciculata

Back 89

Middle and widest layer:
Secretes glucocorticoids cortisol and corticosterone.

Controleld in large part by the HPA axis via ACTH

Front 90

89. Zona reticularis

Back 90

Deep layer:
Secretes the adrenal androgens DHEA and androstenedione.

Also regulated by ACTH, although other factors such as cortical androgen-stimulating hormone from the pituitary may be involved.

Front 91

90. Synthesis of adrenocortical hormones

Back 91

From cholesterol via de novo from small amounts of acetate, and 80% of the cholesterol used for steroid synthesis comes from LDL in the plasma

ACTH stimulates adrenal steroid synthesis but increasing the # of adrenocortical cell receptors for LDL

Once cholesterol enters the cells, it is delivered to the mitochondria where it is cleaved by cholesterol desmolase to form pregnenolone.

Front 92

91. Difference btwn cortisol and aldosterone

Back 92

Cortisol has a keto-oxygen on carbon 3 and is hydroxlated at carbon 11 and 21

Aldosterone has an oxygen atom bound at carbon 18

Front 93

92. Mineralocorticoids

Back 93

1. Aldosterone (very potent)
2. Desoxycorticosterone (1/30 as potent as aldosterone)
3. Corticosteone (slight mineralocorticoid activity)
4. 9α-Fluorocortisol (synthetic, slightly more potent than aldosterone)
5. Cortisol (very slight mineralocorticoid activity)
6. Cortisone (synthetic, slight mineralocorticoid activity)

Front 94

93. Glucocorticoids

Back 94

1. Cortisol (very potent)
2. Corticosterone (way less potent than cortisol)
3. Cortisone (synthetic, almost as potent as cortisol)
4. Prednisone (synthetic, 5x as potent as cortisol
5. Dexamethasone (synthetic, 30x a potent as cortisol)

Front 95

94. Metabolization of adrenocortical hormones

Back 95

Degraded mainly in the liver and conjugated especially to glucuronic acid and to a lesser extent, sulfates.

About 25% are excreted in the bile and then in the feces.

Front 96

95. Function of aldosterone

Back 96

1. Increases renal tubular Excretion of potassium
2. Increases renal tubular Resorption of sodium and chloride
3. Maintenance of total extracellular fluid volume

*Major mineralocorticoid secreted by the adrenals

Front 97

96. Aldosterone and plasma sodium concentration

Back 97

Although it has a potent effect in decreasing the rate of sodium ion excretion by the kidneys, the concentration of sodium in the extracellular fluid often rises only a few milliequivalents.

This is b/c of the simultaneous osmotic resorption of water in the kidney tubules due to the increased sodium concentration. Also, small increases in sodium concentration stimulates thirst and increased water intake. Thus, the sodium concentration maintained

Front 98

97. Aldosterone and arterial pressure

Back 98

An aldosterone mediated increase in extracellular fluid volume lasting more than 1-2 days leads to an increase in arterial pressure which increases kidney excretion of salt and water, called "pressure natriuresis" and "pressure diuresis", respectively.

Front 99

98. Aldosterone escape

Back 99

The return to normal of salt and water excretion by the kidneys as a result of pressure natriuresis and diuresis.

Front 100

99. Excess aldosterone

Back 100

1. Hypokalemia
2. Muscle weakness

Front 101

100. Too little aldosterone

Back 101

1. Hyperkalemia
2. Cardiac toxicity

Front 102

101. Hypokalemia

Back 102

When the potassium ion concentration falls below about 2 mEq/L and causes muscle weakness due to the alteration of the electrical excitability of the nerve and muscle fiber membranes which prevents the transmission of normal action potentials.

Front 103

102.Excess aldosterone can also cause

Back 103

A mild degree of alkalosis due to the increase in tubular hydrogen ion secretion

Front 104

103. Effect of aldosterone on sweat and salivary glands

Back 104

Both glands form a primary secretion that contains sodium chloride but much of the sodium chloride, on passing thru the excretory ducts, is reabsorbed, while potassium and bicarbonate ions are secreted.

Its effect on the sweat glands is important to conserve body salt in hot environments and the effect on the salivary glands is to conserve salt when excessive quantities of saliva are lost.

Front 105

104. Sodium-potassium adenosine triphosphatase

Back 105

Aldosterone causes an increase in the enzyme sodium-potassium adenosine triphosphatase, which serves as the principal part of the pump for sodium and potassium exchange at the basolateral membranes of the tubular cells.

Front 106

105. Epithelial sodium channel proteins

Back 106

Inserted into the luminal membrane of th esame tubular cells that allows rapid diffusion of the sodium ions from the tubular lumen into the cell; then the sodium is pumped the rest of the way by the sodium-potassium pump.

Front 107

106. Evidence of nongenomic actions of aldosterone

Back 107

Aldosterone has been shown to increase formation of cAMP in vascular smooth muscle cells and in epithelial cells of the renal collecting tubules in less than two minutes.

This time period is far too short for gene transcription and translation of proteins.

Front 108

107. Four factors that play an important role in the regulation of aldosterone

Back 108

1. Increased potassium ion concentration in the extracellular fluid increases aldosterone secretion
2. Increased activity of the renin-angiotensin system also increases aldosterone secretion

3. Increased sodium ion concentration in the extracellular fluid very slightly decreases aldosterone secretion
4. ACTH from the anterior pituitary gland is necessary for aldosterone secretion but has little effect in controlling the rate of secretion

Front 109

108. Activation of the renin-angiotensin system

Back 109

Usually occurs in response to diminished blood flow to the kidneys or to sodium loss

Activation results in a severalfold increase in aldosterone secretion

Front 110

109. Blocking the formation of angiotensin II

Back 110

Markedly decreases plasma aldosterone concentration without significantly changing cortisol concentration.

This demonstrates the important role of Ang II in stimulating aldosterone secretion during sodium depletion

Front 111

110. Function of glucocorticoids

Back 111

Helps resist different types of physical or mental stress and minor illnesses.

At least 95% of the glucocorticoid activity of the adrenocortical secretions results from the secretion of cortisol, known also as hydocortisone.

Front 112

111. Effects of cortisol on carbohydrate metabolism

Back 112

1. Stimulation of gluconeogenesis
2. Decreased glucose utilization by cells
3. Elevated blood glucose concentration

Front 113

112. How does cortisol stimulate gluconeogenesis?

Back 113

1. Cortisol increases the enzymes required to convert amino acids into glucose in the liver cells.
2. Cortisol causes mobilization of amino acids from the extrahepatic tissues mainly from muscle.

Front 114

113. How does cortisol decrease glucose utilization by cells?

Back 114

Most physiologist believe that glucocorticoids depress the oxidation of NADH to form NAD+. Because NADH must be oxidized to allow glycolysis, the effect could account for the diminished utilization of glucose by the cells.

Front 115

114. How does cortisol cause elevated blood glucose concentration?

Back 115

The increased rate of gluconeogenesis and reduction in the rate of the utilization of glucose by the cells causes the blood glucose to rise.

Sometimes this rise is occasionally great enough that the condition is called adrenal diabetes.
-Insulin lowers the blood glucose concentration only a moderate amount in this case b/c the tissues are resistant to the effects of insulin (due to the glucocorticoids)

Front 116

115. What are the effects of cortisol on protein metabolism?

Back 116

1. Reduction in cellular protein
2. Increases liver and plasma proteins
3. Increased blood AAs, diminishes transport of AAs into extrahepatic cells, and enhances transport into hepatic cells

Front 117

116. Where is the exception to the reduction in cellular protein with cortisol?

Back 117

In the liver, which may cause:

1. increased rate of deamination fo AAs by the liver
2. increased protein synthesis in the liver
3. increased formation of plasma proteins by the liver
4. increased conversion of AAs to glucose (enhanced gluconeogenesis)

Front 118

117. What are the effects of cortisol on fat metabolism?

Back 118

1. Mobilization of fatty acids from adipose tissue and enhances the oxidation of fatty acids in the cells
2. Obesity is caused by excess cortisol

Essentially, the increased mobilization of fats helps shift the metabolic systems of cells to use fatty acids in times of starvation or other stresses instead of glucose

Front 119

118. How is cortisol important in resisting stress and inflammation?

Back 119

Any stress increases ACTH secretion by anterior pituitary gland which causes cortisol secretion.

The rapid mobilization of AAs and fats make them immediately available for energy and for synthesis of other compounds needed by different tissues of the body.

Front 120

119. What are the two main anti-inflammatory effects of cortisol?

Back 120

1. It can block the early stages of the inflammatory process before inflammation even begins

2. If inflammation has already begun, it causes rapid resolution of the inflammation and increased rapidity of healing.

Front 121

120. How does cortisol prevent inflammation

Back 121

1. It stabilizes the lysosomal membranes which prevent lysosomes from rupturing
2. Decreases the permeability of the capillaries
3. Decreases both migration of white blood cells and phagocytosis
4. Suppresses the immune system, causing lymphocyte reproduction to decrease markedly
5. Attenuates fever mainly b/c it reduces the release of IL-1 from the white blood cells

Front 122

121. How does cortisol resolve inflammation?

Back 122

It blocks most of the facts that promote inflammation and enhances the rate of healing due to the mobilization of AAs and uses these to repair the damaged tissue.

Front 123

122. What are some other effects of cortisol?

Back 123

1. Blocks the inflammatory response to allergic reactions

2. Decreases the number of eosinophils and lymphocytes in the blood

3. Large doses of cortisol causes atrophy of all the lymphoid tissue in the body

4. Increases red blood cell production

Front 124

123. ACTH

Back 124

Controls secretion of cortisol.

Secreted by anterior pituitary gland

It is a large polypeptide w/a chain length of 39 AAs

Front 125

124. How is ACTH release controlled?

Back 125

The corticotropin-releasing factor (CRF) is secreted from the paraventricular nucleus of the hypothalamus and then carried to the anterior pituitary gland where it induces ACTH secretion.

Front 126

125. ACTH and second messengers

Back 126

Principal effect of ACTH on adrenocortical cells is the activation of adenylyl cyclas which induces formation of cAMP

Also causes activation of the enzyme protein kinase A, which causes the initial conversion of cholesterol to pregnenolone*

*This is the rate limiting step for all the adrenocortical hormones

Front 127

126. Where does cortisol have negative feedback inhibition?

Back 127

1. Hypothalamus to decrease the formation of CRF

2. Anterior pituitary gland to decrease the formation of ACTH

*Stress can break through this negative feedback causing excessive cortisol secretion

Front 128

127. Addison's disease

Back 128

Results from a failure of the adrenal cortices to produce adrenocortical hormones and this in turn is most freq caused by primary atrophy of the adrenal cortices

It causes:
1. Mineralocorticoid deficiency
2. Glucocorticoid deficiency
3. Melanin pigmentation
4. Possible "addisonian crisis

Front 129

128. Symptoms of Addison's disease

Back 129

1. Progressive weakness and easy fatigability
2. GI disturbances
3. Loss of appetite
4. Weight loss
5. Hyperpigmentation of skin
6. Hyperkalemia
7. Hypernatremia
8. Volume depletion
9. Hypotension

Front 130

129. Treatment of Addison's disease

Back 130

An untreated person w/total adrenal destruction dies w/in a few days to a few weeks due to weakness and circulatory shock.

Person can live for years if small quantities of mineralocorticoids and glucocorticoids are administered daily

Front 131

130. Addisonian crisis

Back 131

In a person w/Addison's disease, the output of glucocorticoids does not increase during stress; this person is likely to have an acute need for excessive amounts of glucocorticoids to prevent death.

Front 132

131. Cushing's syndrome (Hyperadrenalism)

Back 132

Hypersecretion by the adrenal cortex due to:
1. Adenomas of the anterior pituitary gland that secretes large amount of ACTH which causes adrenal hyperplasia
2. Abnormal function of the hypothalamus that causes high levels of CRF which stimulates ACTH release
3. Ectopic secretion of ACTH by a tumor elsewhere in the body
4. Adenomas of the adrenal cortex

Front 133

132. Characteristics of Cushing's syndrome

Back 133

1. Central obesity (about trunk and upper back)
2. Moon faces
3. Weakness and fatigability
4. Hirsutism
5. Hypertension
6. Plethora
7. Glucose intolerance/diabetes
8. Osteoporosis
9. Neuropsychiatric abnormalities
10. Menstrual abnormalities
11. Skin striae

Front 134

133. Pituitary Cushing syndrome

Back 134

The most common form

ACTH levels are elevated and cannot be suppressed by the administration of low dose dexamethasone but the pituitary then responds to higher doses of injected dexamethasone

Front 135

134. Ectopic ACTH Cushing syndrome

Back 135

Results in an elevated ACTH but its secretion is completely insensitive to low or high doses of dexamethasone

Front 136

135. Adrenal tumor Cushing syndrome

Back 136

The ACTH level is quite low b/c of feedback inhibition of the pituitary.

Both low and high does dexamethasone fail to suppress cortisol excretion

Front 137

136. Cushing syndrome effects on carbohydrate and protein metabolism

Back 137

Abudance of cortisol can caused increased blood glucose concentration and high levels of glucocorticoids cause protein catabolism which results in severe weakenss.

Front 138

137. Treatment of Cushing syndrome

Back 138

Consists of removing an adrenal tumor if this is the cause or decreasing the secretion of ACTH if this is possible.

If ACTH secretion cannot easily be decreased, the only satisfactory treatment is usually bilateral partial or total adrenalectomy.

Front 139

138. Conn's syndrome (Primary Aldosteronism)

Back 139

An autonomous overproduction of aldosterone, with resultant suppression of the renin-angiotensin system.

It results in:
1. Hypokalemia
2. Increase in extracellular fluid volume and blood volume
3. Almost always, hypertension
4. Occasional periods of paralysis caused by hypokalemia.

Front 140

139. Causes of primary aldosteronism

Back 140

1. Adrenocortical neoplasm that produces large amounts of aldosterone
2. Primary adrenocortical hyperplasia
3. Glucocorticoid--remediable hyperaldosteronism which leads to a sustained production of hybrid steroids in addition to both cortisol and aldosterone.

Front 141

140. Dx criteria of primary aldosteronism

Back 141

Decreased plasma renin concentration

Front 142

141. Treatment of primary aldosteronism

Back 142

Surgical removal of the tumor or most of the adrenal tissue when hyperplasia is the cause.

Front 143

142. Androgenital syndrome

Back 143

Due to an excessive quantity of androgens that cause intense masculinizing effects throughout the body.

The excretion of 17-ketosteroids in the urine are 10 to 15x normal which is the useful in the diagnosis of this disease.

Front 144

143. Three distinctive hyperadrenal clinical syndromes

Back 144

1. Cushing syndrome

2. Hyperaldosteronism

3. Adrenogenital syndrome

Front 145

144. Cortical carcinomas vs. adenomas or hyperplastic processes

Back 145

Cortical carcinomas tend to produce more marked hypercortisolism, are larger in size when compared to the adenomas or hyperplastic processes

Front 146

145. Where do a majority of hyperplastic adrenals arise from?

Back 146

From secondary influences; primary cortical hyperplasia is uncommon

Front 147

146. Congenital adrenal hyperplasia (CAH)

Back 147

Represents a group of autosoma-recessive, inherited metabolic errors, each characterized by a deficiency of total lack of a particular enzyme involved in the biosynthesis of cortical steroids, particularly cortisol.

Steroidogenesis is then channeled into other pathways, leading to increased production of androgens, which accounts for virilization.

Also, the decrease in cortisol results in the increased secretion of ACTH, resulting in adrenal hyperplasia.

Front 148

147. 21-Hydroxylase deficiency

What are the three distinctive syndromes associated w/this deficiency?

Back 148

Defective conversion of progesterone to 11-deoxycorticosterone by 21-hydroxylase (CYP21B) accounts for over 90% of cases of CAH.

May range from a total lack to a mile loss.

Associated with:
1. Salt-wasting (classic) adrenogenitalism
2. Simple virilizing adrenogenitalism
3. Nonclassic adrenogenitalism

Front 149

148. Mechanism of CYP21B gene inactivation

Back 149

Involved recombination w/a neighboring pseudogene on chromosome 6p21 called CYP21A.

In th emajority of cases of CAH, portions of the CYP21A pesudogene replace all or part of the active CYP21B gene.

The intro of nonfunctional sequences from CYP21A into the CYP21B sequence has the same effect as inactivating mutations in CYP21B.

Front 150

149. Salt-wasting (classic) adrenogenitalism

Back 150

Results from an inability to convert progesterone into deoxycorticosterone b/c of a total lack of the hydroxylase (21-Hydroxylase).

Thus, there is no synthesis of mineralocorticoids and deficient cortisol synthesis.

Causes:
1. Salt wasting
2. Hypnatremia
3. Hyperkalemia
4. Acidosis
5. Hypotension
6. Cardiovascular collapse
7. *Virilization*

Front 151

150. Male vs. female differences in virilization in Salt-wasting adrenogenitalism

Back 151

Females have a range of mild clitoral enlargement to complete labioscrotal fusion to marked clitoral enlargement enclosing the urethra, thus producing a phalloid organ

Males with this disorder are generally unrecognized at birth but come to clinical attention 5 to 15 days later b/c of some salt losing crisis.

Front 152

151. Simple virilizing adrenogenitalism

Back 152

(Without salt wasting)

Presents w/genital ambiguity and may occur in individuals w/a less than total 21-Hydroxylase defect b/c the level of mineralocorticoids, although reduced, is sufficient for salt reabsorption.

However, the lowered glucocorticoid level fails to cause feedback inhibition of ACTH secretion.

Thus, testosterone is increased, and ACTH is elevated, with adrenal hyperplasia.

Front 153

152. Nonclassic adrenogenitalism

Back 153

Much more common than the other syndromes; patients may be virtually asymptomatic or have mild manifestations, such as hirsutism.

Dx can be made only by demonstration of biosynthetic defects in steroidogenesis and by genetic studies.

Front 154

153. Neonates w/ambiguous genitalia

Back 154

CAH should be suspected in any neonate w/ambiguous genitalia.

Front 155

154. Treatment of CAH

Back 155

Treated w/exogenous glucocorticoids, which in addition to providing adequate levels of glucocorticoids, also suppress ACTH levels and thus decrease the excessive synthesis of steroid hormons responsible for many clinical abnormalities.

Front 156

155. Three patterns of adrenocortical insufficiency

Back 156

1. Primary acute adrenocortical insufficiency (adrenal crisis)
2. Primary chronic adrenocortical insufficiency (Addison disease)
3. Secondary adrenocortical insufficiency

Front 157

156. Primary acute adrenocortical insufficiency

Back 157

May be caused by either primary adrenal disease (primary hypoadrenalism) or decreased stimulation of the adrenals owing to a deficiency of ACTH (secondary hypoadrenalism)

Occurs in:
1. Adrenal crisis
2. Patients maintained on exogenous corticosteroids
3. Massive adrenal hemorrhage

Front 158

157. Waterhouse-Friderichsen syndrome

Back 158

1. Overwhelming bacterial infection
2. Rapidly progressive hypotension leading to shock
3. Disseminated intravascular coagulation w/widespread purpura
4. Rapidly developing adrenocortical insufficiency associate w/massive bilateral adrenal hemorrhage

The adrenals are converted to sacs of clotted blood virtually obscuring all underlying detail.

Front 159

158. What are the four most common causes of primary adrenal insufficiency?

Back 159

1. Autoimmune adrenalitis
2. Tuberculosis
3. AIDS
4. Metastatic cancers

Front 160

159. Primary chronic adrenocortical insufficiency

Back 160

Known as Addison disease; results from progressive destruction of the adrenal cortex.

Front 161

160. Secondary adrenocortical insuffiency

Back 161

Any disorder of the hypothalamus and pituitary that reduces the output of ACTH leads to a syndrome of hypodrenalism that has many similarities to Addison disease.

Prolonged administration of exogenous glucocorticoids suppresses the output of ACTH and adrenal function.

With secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low

Also, the adrenals may be moderately to markedly reduced in size.

Front 162

161. Adrenocortical adenomas

Back 162

Clinically silent and are usually encountered as incidental findings at times of autopsy or during abdominal imaging.

There are two types; functional and non-functional;

Functional are associated w/atrophy of the adjacent cortex

Front 163

162. Adrenocortical carcinomas

Back 163

Rare neoplasms that can occur at any age, including childhood

More likely to be functional than adenomas are, and carcinomas are therefore often associated w/virilism or hyperadrenalism.

Invasion of contiguous structions, including the adrenal vein and IVC, is common.

May be difficult to differentiate from carcinoma that metastatized to the adrenals.

Front 164

163. Two inherited causes of adrenal cortical carcinomas

Back 164

1. Li-Fraumeni syndrome

2. Beckwith-Wiedemann syndrome

Front 165

164. Adrenal cysts

Back 165

Relatively uncommon lesions.

They may produce an abdominal mass and flank pain.

Both cortical and medullary neoplasms may undergo necrosis and cystic degeneration and may present as non-functional cysts.

Front 166

165. Adrenal myelolipomas

Back 166

Unusual benign lesions composed of mature fat and hematopoietic cells.

May be seen in cortical tumors and in adrenals with cortical hyperplasia

Front 167

166. What is the rate-limiting step in the synthesis of cortisol?

Back 167

The conversion of cholesterol to pregnenolone

Front 168

167. What oxidase enzyme catalyzes each step in the pathway of adrenocortical hormone synthesis?

Back 168

Mitochondrial cytochromes; similar to the liver P450 oxidase system.

Front 169

168. Why does the zona fasciculata synthesize cortisol, but not aldosterone or androgens?

Back 169

The enzymes required for cortisol synthesis, such as steroid 11β-hydroxylase, are expressed in the zona fasciculata, whereas enzymes required for aldosterone and androgen synthesis are not.

Front 170

169. What are the most important plasma proteins that binds cortisol?

Back 170

Corticosteroid-binding globulin (CBG) and albumin

CBG has a high affinity for cortisol but low overall capacity, whereas albumin has low cortisol affinity but high overall capacity

Front 171

170. Where are the primary sites of peripheral cortisol metabolism?

Back 171

1. Liver
2. Kidneys

Front 172

171. Type I vs. Type II glucocorticoid receptors

Back 172

Mineralocorticoid receptors

Expressed in the organs of excretion (kidney, colon, salivary glands, sweat glands)

Type II receptors, on the other hand, have a broader tissue distribution

Front 173

172. Regulation of cortisol production

Back 173

1. Neurons from the hypothalamus secrete CRH
2. CRH binds to the G-protein receptors on the anterior pituitary gland
3. CRH binding stimulates production of proopiomelanocortin (POMC)
4. Cleavage of POMC yields ACTH and melanocyte stimulating hormone (MSH)
5. ACTH promotes synthesis of cortisol
6. High cortisol levels decrease synthesis and release of CRH and ACTH

Front 174

173. Why is tapering to a lower dosage of exogenous glucocorticoids necessary?

Back 174

If not tapered, can result in sondary adrenal insufficiency

Necessary to allow the HPA axis to regain full activity.

Exogenous glucocorticoids cause atrophy of the adrenal cortex

Front 175

174. Cortisol analogues

Back 175

1. Prednisone
2. Prednisolone
3. Fludrocortison
4. Dexamethasone

Front 176

175. Glucocorticoid receptor agonists

Back 176

Mimic cortisol function by acting as agonists at the glucocorticoid receptor

1. Prednisone
2. Prednisolone
3. Methyprednisolone
4. Dexamethasone
5. Hydrocortisone
6. Fluticasone
7. Beclomethasone
8. Flunisolide
9. Triamcinolone
10. Budesonide

Front 177

175. Clinical application of glucocorticoid receptor agonists

Back 177

1. Inflammatory conditions in many different organs

2. Autoimmune diseases

3. Replacement therapy for primary and secondary adrenal insufficiency

Front 178

176. Adverse effects of glucocorticoid receptor agonists

Back 178

1. Immunosuppression
2. Hyperglycemia
3. Hypercortisolism
4. Impaired wound healing
5. Hypertension
6. Fluid retention
7. Inhaled oropharyngeal candidiasis

Front 179

177. Contraindications of glucocorticoid receptor agonists

Back 179

Systemic fungal infection

Front 180

178. Inhaled glucocorticoids

Back 180

1. Fluticasone
2. Beclomethasone
3. Flunisolide
4. Triamcinolone
5. Budesonide

*Inhaled formulations greatly reduce systemic adverse effects; do not switch abruptly from high-dose oral to inhaled glucocorticoids

Front 181

179. Glucocorticoid receptor antagonists

Back 181

Competitive antagonist of cortisol action at the glucocorticoid receptor

Mifepristone (RU-486)

Front 182

180. Clinical application of glucocorticoid receptor antagonists

Common adverse effects?

Back 182

Causes abortion (through day 49 of pregnancy)

Also, at high doses, it could potentially be useful in the treatment of ectopic ACTH syndrome

Can result in prolonged bleeding time, bacterial infections, sepsis, nausea, vomiting, diarrhea, cramps, vaginal bleeding, headache

Front 183

181. Contraindications of glucocorticoid receptor antagonists

Back 183

1. Chronic adrenal failure
2. Ectopic pregnancy
3. Hemorrhagic disorders
4. Anticoagulation theraphy
5. Intrauterine devices

Front 184

182. Inhibitors of glucocorticoid synthesis

Back 184

Inhibits various steps in the glucocorticoid hormone biosynthesis

Includes:
1. Mitotane
2. Aminoglutethimide
3. Metyrapone
4. Trilostane
5. Ketoconazole

Front 185

183. Mitotane

Back 185

Used in medical adrenalectomy in cases of severe Cushing syndrome or adrenocortical CA

Can cause visual disturbances, and hemorrhagic cystitis

Also can cause hypercholesterolemia

Contraindications is the Live rotavirus vaccine

Structural analogue to DDT that is toxic to adrenocortical mitochondria

Front 186

184. Aminoglutethimide

Back 186

Used to treat Cushing's syndrome

Can cause:
Cortisol insufficiency, agranulocytosis, leukopenia, neutropenia, pancytopenia, pruritus, hypotension.

Contraindicated in hypersensitivity to glutethimide or aminoglutethimide

Inhibits side chain cleavage enzyme as well as aromatase, which is important for conversion of androgens to estrogens

Front 187

185. Metyrapone

Back 187

Used for Dx evaluation of HPA axis and in Cushing's syndrome

Can cause cortisol insufficiency and hypertension

Contraindicated with adrenal cortical insufficiency

Inhibits 11β-hydroxylation, resulting in impaired cortisol synthesis

Can also result in disinhibition of ACTH secretion

Front 188

186. Trilostane

Back 188

Used in Cushing's syndrome and aldosteronism

Can cause an Addisonian crisis, postural hypotension, hypoglycemia

Contraindicated w/adrenal cortical insufficiency, and renal or hepatic dysfunction

Reversible inhibitor of 3β-hydroxysteroid dehydrogenase, which reduces aldosterone and cortisol production in the adrenal cortex

Front 189

187. Mineralocorticoid receptor agonists

Back 189

Agonist at the mineralocorticoid receptor

Fludrocortisone

Front 190

188. Fludrocortisone

Back 190

Used in hypoaldosteronism

Can cause hypertension, hypokalemia, heart failure, thrombophlebitis, secondary hypocortisolism, edema, rash, hyperglycemia

Contraindicated w/systemic fungal infection

Adverse effects are related to its ability to mimic a state of mineralocorticoid excess

Front 191

189. Mineralocorticoid receptor antagonists

Back 191

Competetive antagonist of aldosterone action at the mineralocorticoid receptor

Includes:
1. Spironolactone
2. Eplerenone

Front 192

190. Adrenal sex steroid (DHEA)

Back 192

DHEA is a prohormone that is converted to testosterone in the periphery

Used in hypoaldosteronism and in chronic fatigue syndrome

Can cause acne, hepatitis, hirsutism, androgenization

Contraindicated w/breat, ovarian or prostate CA

May be used as replacement therapy for cases of Addison's disease w/documented DHEA deficiency.