15.8 - 15.10: Parathyroid gland, Endocrine pancreas, adrenal cortex / medulla Flashcards Preview

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Flashcards in 15.8 - 15.10: Parathyroid gland, Endocrine pancreas, adrenal cortex / medulla Deck (171):
1

What is the key cell within the parathyroid gland? What does this do?

-Chief cell
-Regulates *free* ionized calcium in the serum via PTH secretion

2

What percent of the Ca in the body is bound to proteins?

60%

3

What is the effect of PTH on the bones? How?

Increases osteoclast activity, by first activating osteoBLASTS, which then activate osteoclasts

4

What is the effect of PTH on the small bowel? How?

Increases small bowel reabsorption of Ca and Phosphate through vitamin D

5

What is the effect of PTH on the kidneys?

Increases renal calcium reabsorption, and decreases phosphate reabsorption

6

What are the cells that secrete bone? Resorb bone?

Secrete = Osteoblasts
Resorb = Osteoclasts

7

How are osteoclasts activated?

Osteo*blasts* receive PTH signal, which then activate osteoclasts

8

Why is it important that PTH increases the excretion of phosphate?

Phosphate binds free Ca, so getting rid of it increases free Ca levels within the serum

9

What is primary hyperparathyroidism?

Excess PTH d/t a disorder of the parathyroid gland itself

10

What is the most common cause of primary hyperparathyroidism?

Parathyroid adenoma

11

True or false: a parathyroid adenoma is benign

True

12

Do parathyroid adenomas usually involve more than one gland?

No

13

What is the most common presentation of a parathyroid adenoma?

Asymptomatic hypercalcemia

14

What are the kidney problems that can arise from a parathyroid adenoma? (2)

-Nephrolithiasis (Ca oxalate stones)
-Nephrocalcinosis

15

What are the GI problems that can arise from a Parathyroid adenoma? (3)

-Constipation
-PUD
-acute pancreatitis

16

What is nephrocalcinosis?

Deposition of Ca into the tubules of the kidney, resulting in polyuria

17

What are some of the CNS disturbances that can be caused by hypercalcemia from a parathyroid adenoma?

Seizures
Depression

18

How can hypercalcemia cause acute pancreatitis?

Ca activates the enzymes in the pancreas

19

What is osteitis fibrosa cystica?

Resorption of Ca from the bone causes cyst formation in the bones

20

What happens to the following lab values with hyperparathyroidism:
-PTH
-Serum Ca
-Serums phosphate
-Urinary cAMP
-Serum alk phos

-PTH (increased)
-Serum Ca (increased)
-Serums phosphate (decrease)
-Urinary cAMP (increase)
-Serum alk phos (increase)

21

How does hyperparathyroidism cause increased urinary cAMP?

Gs coupled protein activation by PTH

22

What is the role of alk phos in bone normally? Why is it increased in hyperparathyroidism?

-Normally aids in the deposition of Ca onto bone by generating an alkaline environment

-Since PTH first activates osteoblasts, these cells secrete alk phos

23

What is the treatment for a hyperparathyroidism secondary to a parathyroid adenoma?

Surgical removal of the affected gland

24

What is secondary hyperparathyroidism?

Excess production of PTH d/t disease process extrinsic to the parathyroid gland

25

What is the most common cause of secondary hyperparathyroidism?

Chronic renal failure

26

How does chronic renal failure lead to hyperparathyroidism?

Decreased phosphate excretion leads to increased serum levels of phosphate, which binds Ca. Lower Ca levels then stimulate the parathyroid gland

27

What is the effect of a lack of phosphate excretion in chronic renal disease in terms of PTH secretion?

Higher phosphate leads to lower Ca, leading to increased PTH levels

28

What happens to the following lab values with secondary hyperparathyroidism:
-PTH
-serum ca
-serum phosphate
-alk phos

-Increased PTH
-Decreased serum Ca
-Increased serum phosphate
-Increased alk phos

29

What are the three major causes of hypoparathyroidism?

-Autoimmune damage
-Surgical excision
-DiGeorge syndrome

30

Which pharyngeal pouches fail to develop in DiGeorge syndrome? What is the genetic cause of this?

3rd and 4th

chr 22q del

31

What are the s/sx of hypoparathyroidism?

-Numbness and tingling
-Muscle spasms (tetany)

32

What happens to serum PTH and Ca levels with pseudohypoparathyroidism?

Both decreased

33

Where specifically does the numbness/tingling start with hypoparathyroidism?

Lips

34

What is the trousseau sign?

a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm.

35

What is Chvostek sign?

a clinical sign of existing nerve hyperexcitability (tetany) seen in hypocalcemia. It refers to an abnormal reaction to the stimulation of the facial nerve. When the facial nerve is tapped at the angle of the jaw (i.e. masseter muscle), the facial muscles on the same side of the face will contract momentarily (typically a twitch of the nose or lips) because of hypocalcemia

36

What is pseudohypoparathyroidism?

When end-organs do not respond to PTH d/t a mutation in the Gs protein

37

What are the PTH and Ca levels with pseudohypoparathyroidism?

Hypocalcemia and increased PTH levels

38

What is the inheritance of pseudohypoparathyroidism? What are the physical deformities that can present with this?

AD

Short stature + short 4th and 5th digits

39

What are the cells that comprise the endocrine pancreas called?

Islets of Langerhans

40

What does a single islet of Langerhans contain?

multiple cells types, each producing one hormone type

41

What cells of the pancreas secrete insulin? Where are these cells in the islets?

-beta cells
-Center of islets

42

What cells of the pancreas secrete glucagon?

Alpha cells

43

Where in the islets of langerhans do the beta cells lie?

Center

44

What is the MOA of insulin?

Increases the movement of GLUT 4 receptors to the surface of cells

45

What type of hypersensitivity rxn occurs in type I DM?

Type IV

46

What are the HLA haplotypes associated with DM I?

DR3 and DR4

47

What is the classic histological finding of DM I?

Inflammation of the islets

48

What are the autoantibodies that can be seen with DM I?

against insulin

49

What causes the muscle wasting with untreated DM I?

Increased gluconeogenesis from amino acids

50

What are the risk factors for DKA?

Stress
Infection

51

How does stress cause DKA?

Epinephrine increases glucagon, exacerbating lipolysis

52

What are the three ketone bodies that are found in DKA?

-beta-hydroxybutyrate
-acetone
-acetoacetic acid

53

What, besides hyperkalemia, are the lab findings with DKA?

-Anion gap metabolic acidosis
-Hyperkalemia

54

What are the s/sx of DKA? What type of respirations?

-Kussmaul respiration
-Dehydration
-N/v
-mental status changes

55

Why the anion gap metabolic acidosis with DKA?

Increased ketonic acids

56

Why is there hyperkalemia with DKA? (2)

-Insulin causes K to go into cells, but there is none
-K is exchanged for H+ in the serum

57

True or false: despite having high potassium levels in the serum, DKA pts actually have lower K levels overall

True

58

What are the three measures to take to treat DKA?

-IVF
-Insulin
-Replace lytes

59

How can treating DKA lead to hypokalemia?

-Insulin will force K into cells
-Reversal of the acidosis

60

What is the classic DM II pt?

Obese middle aged adult

61

True or false: there is a strong genetic predisposition for DM II

True

62

How does DM II arise?

Decreased numbers of insulin receptors

63

Which has a stronger genetic inheritance, type 1 or 2 DM?

2

64

What are the histological findings of DM II?

Islets of Langerhans are filled with amyloid

65

What are the ssx of DM II, if any?

-Polyuria
-Polydipsia
-Hyperglycemia

66

What are the clinical values for random and fasting glucose levels to diagnose DM II?

-Random more than 200 mg/dL
-Fasting more than 126 mg/dL

67

What is the glucose tolerance test?

More than 200 mg/dL two hours after glucose load

68

What is the first line therapy for DM II?

Weight loss

69

What are the pharmacological treatments for DM II? (2)

-Drug therapy to counter insulin resistance

-Insulin

70

When in the progression of DM II do pts become insulin dependent?

end stages

71

What is hyperosmolar nonketotic coma? Why are there no ketones with this?

-High glucose levels cause dehydration, leading to hypotension and coma.

-No ketones since there is still a small amount of insulin to counter glucagon

72

What are the two major ways that complications from DM arise?

-Non-enzymatic glycosylation of BM
-Osmotic damage

73

How is CVD mediated in DM II?

NEG of large and medium sized vessels leads to atherosclerosis

74

NEG of small vessels in DM II leads to what?

Hyaline arteriolosclerosis

75

What is HbA1c?

Glycosylated Hb

76

How does DM II mediated CKD?

Efferent arteriole of the kidney preferentially undergoes NEG, causing a hyperfiltration state, causing sclerosing of the mesangium

77

What happens if there is hyaline deposition in the afferent arteriole of the kidney?

Diffuse sclerosis of the glomerulus from loss of blood supply

78

How does peripheral neuropathy develop in DM?

Schwann cells take up glucose independent of insulin. This glucose is converted to sorbitol, which leads to osmotic damage.

Recall that schwann cells myelinate peripheral nerves

79

What is the enzyme that converts glucose to sorbitol?

Aldose reductase

80

What are the three cells in the body that can take up glucose without insulin?

-Schwann cells
-Pericytes of the retinal blood vessels
-Lens

81

How can DM cause blindness?

Pericytes of the retinal blood vessels take up glucose, convert it to sorbitol, and die. Aneurysms and bleeding then form

82

How do cataracts result from DM?

Lens cells take up glucose, convert it to sorbitol via aldose reductase, which causes osmotic damage

83

What cells do pancreatic endocrine tumors arise from?

Islet cells

84

Pancreatic endocrine tumors are often a component of what genetic malignancy? What other malignancies are associated with this?

-MEN1

-Parathyroid hyperplasia
-Pituitary adenoma
-Pancreatic tumors

85

What are the s/sx of an insulinoma?

Episodic hypoglycemia with mental status changes and are relieved by glucose

86

What are the levels of the following in an insulinoma:
-Glucose
-insulin
-C-peptide

-Decreased glucose
-Increased insulin
-Increased C-peptide

87

What is Zollenger-Ellison syndrome?

gastrinoma that produces gastrin to increased HCl from parietal cells

88

What are the GI findings of a somatostatinoma?

-Achlorhydria (inhibition of gastrin)
-Cholelithiasis and steatorrhea (inhibition of CCK)

89

How do somatostatinomas cause cholelithiasis?

Somatostatin inhibits CKK action on the gallbladder

90

What is a VIPoma?

Tumor that causes and excessive vasoactive intestinal peptide to be produced

91

-----
What are the findings of a VIPoma? (2) What electrolyte disturbance?
-----

-Watery diarrhea
-Hypokalemia
-Achlorhydria

92

What is the effect of VIP on gastric acid secretion?

Inhibits

93

What is the effect of VIP on potassium levels?

Lowers

94

What does the adrenal cortex secrete? Medulla?

-Cortex = hormones derived from cholesterol

-Medulla = catecholamines

95

What are the three layers of the adrenal cortex (from superficial to deep)?

-Glomerulosa
-Fasciculata
-Reticularis

96

What part of the adrenal cortex secretes aldosterone?

Glomerulosa

97

What part of the adrenal cortex secretes cortisol?

Fasciculata

98

What part of the adrenal cortex secretes the sex hormones?

Reticularis

99

What does the mnemonic "it gets sweeter as it gets deeper" mean when applied to the adrenal cortex?

-Aldosterone controls salt
-Cortisol controls sugar
-Sex steroids are the sweetest

100

What are the findings of the extremities with cushing's syndrome? Why?

Muscle weakness with thin extremities, due to gluconeogenesis stimulation by cortisol

101

What areas of the body deposit fat with cushing's syndrome?

-Face
-Buffalo hump
-Trunk

102

What, besides obesity, are the superficial abdominal findings with cushing's? Why?

-Abdominal striae
-Cortisol impairs the synthesis of collagen

103

What are the CV findings of Cushing's? Why?

-HTN
-Upregulation of alpha 1 receptors

104

What are the bone problems caused by Cushing's?

Osteoporosis

105

What happens to the immune system with cushing's syndrome?

Suppressed

106

What causes the muscle weakness with Cushing's?

Breakdown of amino acids for gluconeogenesis

107

What causes the abdominal striae with Cushing's?

Cortisol impairs the synthesis of collagen, leading to weak vessels, and thus vessel hemorrhage

108

How does Cushing's cause HTN?

Upregulates alpha 1 receptors on arterioles

109

Why is cortisol essential for life?

Maintains vascular tone

110

What are the three major mechanisms through which cortisol causes immune suppression?

-Inhibits phospholipase A2
-Inhibits IL-2
-Inhibits histamine release from mast cells

111

What is the role of phospholipase A2?

converts arachidonic acid to generate proinflammatory prostaglandins

112

What is the role of IL-2?

T cell growth factor (switch to Th2)

113

How do you diagnose Cushing's syndrome?

24 hours cortisol level monitoring

114

What are the four major causes of Cushing's?

-Exogenous corticosteroids (iatrogenic)
-Primary adrenal adenoma, hyperplasia, or carcinoma
-ACTH secreting pituitary adenoma
-Paraneoplastic ACTH secretion

115

What is the most common cause of Cushing's syndrome?

Iatrogenic 2/2 exogenous corticosteroids

116

What causes the adrenal atrophy with exogenous corticosteroids?

No ACTH to maintain them

117

What are the three types of primary growths that can cause Cushing's syndrome?

-Adenoma
-Hyperplasia
-Carcinoma

118

What will happen to the adrenal gland that is not producing excess cortisol?

Decrease in size

119

What type of pituitary disease can cause Cushing's?

ACTH secreting

120

What is the classic example of a paraneoplastic syndrome that secretes ACTH?

Small lung cell carcinoma

121

What is the thinking behind the high dose dexamethasone test?

-Administering dexamethasone inhibits the production of ACTH by the pituitary adenoma

-but FAILs to suppress ectopic ACTH production by SCLC

122

What are the metabolic disturbances with hyperaldosteronism?

-Hypernatremia
-Hypokalemia
-Metabolic alkalosis

123

What happen to BP with hyperaldosteronism?

HTN

124

Where in the nephron does aldosterone work? MOA?

Late distal tubule of the collecting duct

125

What are the two cell types in the late distal collecting duct?

-Principal cell
-Alpha-intercalated cell

126

What is the role of the principal cell?

Absorbs Na, and secretes K in response to aldosterone

127

What is the role of the alpha-intercalated cell?

Secretes H+ ion in response to aldosterone

128

What are the metabolic disturbances that are seen with hyperaldosteronism?

-Hypokalemia
-Hypernatremia
-Acidosis

129

What is the most common cause of primary aldosteronism? What are the two other, less common, causes?

Adrenal adenoma

Hyperplasia
Carcinoma

130

What happens to renin levels in primary hyperaldosteronism? Why?

Decreased
Increased blood flow to the kidney as a result of increased Na uptake

131

What is the cause of secondary hyperaldosteronism?

Activation of the renin-angiotensin system, leading to increased aldosterone

132

What happens to aldosterone and renin with secondary hyperaldosteronism?

Both increased

133

Increased blood pressure in a young women can be cause be what effect on the kidney?

Fibromuscular Dysplasia of the renal artery

134

What is the primary pathophysiological process that occurs with secondary hyperaldosteronism?

Some insult to the renal arteries decrease blood flow to the kidneys, and therefore increase renin.

Increased renin increases ang II, which increases aldosterone

135

What is congenital adrenal hyperplasia?

Excess sex steroids with hyperplasia of both adrenal glands, due to a defect in the enzymes responsible for steroidogenesis

136

What is the most commonly affected enzyme in congenital adrenal hyperplasia? What is the effect of this? Why?

21-hydroxylase deficiency

Pregnenolone is shunted down the sex hormone pathway, since, since 21-hydroxylase is necessary for the genesis of mineralocorticoids, and cortisol

137

What is cholesterol turned into in the genesis of hormones? What are the three pathways that this molecule can be shunted down?

Pregnenolone to:

-Mineralocorticoids
-Cortisol
-Sex hormones

138

What is the enzyme that is necessary for the production of both mineralocorticoids and cortisol? What happens when this enzyme is deficient/defective?

21-hydroxylase

Pregnenolone is shunted down the sex hormone synthesis pathway

139

What are the physical consequences of 21-hydroxylase deficiency (males and females)?

Clitoral enlargement in female
Precocious puberty in males

140

What causes the adrenal hyperplasia with 21-hydroxylase deficiency?

Since no cortisol is produced, ATCH is upregulated, causing hyperplasia of the adrenals

141

What are the two metabolic/hemodynamic effects of 21-hydroxylase deficiency (congenital adrenal hyperplasia)?

-Low BG
-Hypotension
-salt wasting (hyponatremia and hyperkalemia)
-Clitoromegaly if female

142

What causes the hyponatremia and hyperkalemia with 21 hydroxylase deficiency (congenital adrenal hyperplasia)?

No mineralocorticoids (aldosterone) is produced d/t the lack of enzyme. No aldosterone leads to these two electrolyte disturbances

143

What are the two major enzymes that can cause congenital adrenal hyperplasia? What is the major difference between the two?

21 hydroxylase
11 hydroxylase

11 hydroxylase deficiency does not present with salt wasting, since some mineralocorticoids are able to be produced

144

What is the enzyme that is necessary for the conversion of pregnenolone into either sex hormones or cortisol? What are the problems if there is a deficiency in this enzyme?

17 hydroxylase

No sex hormones and no cortisol produced, but an overabundance of mineralocorticoids, leading to HTN, hypernatremia, and hypokalemia

145

Why is there always adrenal hyperplasia with any sort of enzymatic deficiency of the pregnenolone conversion pathway?

All enzymes needed to produce cortisol.

No cortisol = increased ACTH production = adrenal hyperplasia

146

What is Waterhouse-Friderichsen syndrome?

Acute adrenal insufficiency caused by DIC and necrosis of adrenal glands (usually by Neisseria meningitidis)

147

What is the classical presentation of Waterhouse-Friderichsen syndrome?

Child who gets neisseria meningitis who develops DIC, leading to bilateral necrosis of both adrenal glands, leading to a lack of cortisol and hypotension

148

What is the classic gross finding of the adrenal glands with Waterhouse-Friderichsen syndrome?

Adrenal glands with a large pool of coagulated blood

149

What is chronic adrenal insufficiency? Causes (3)?

Progressive destruction of the adrenal glands, caused by:
-autoimmune attack
-TB
-metastatic carcinoma

150

Cancer from what organ system commonly metastasizes to the adrenal glands to produce chronic adrenal insufficiency?

Lung cancer that metastasizes to the adrenal glands

151

What type of cancer loves to metastasize to the adrenal glands, and cause chronic adrenal insufficiency?

Lung cancer

152

What are the findings of chronic adrenal insufficiency, and what causes them?

-hypotension/hypovolemia
-Hyponatremia
-hyperkalemia

All caused by a lack of aldosterone

153

What causes the hyperpigmentation seen with chronic adrenal insufficiency?

ACTH will increase, which is derived from POMC.

POMC breaks down to form ACTH and MSH. Thus increased MSH results in hyperpigmentation

154

What are the two hormones that POMC is broken down into?

ACTH
MSH (melanocyte stimulating hormone)

155

What causes the n/v/d with chronic adrenal insufficiency?

lack of cortisol

156

What type of cells comprise the adrenal medulla? What are these derived from embryologically?

Neural Crest derived chromaffin cells

157

What is the function of the adrenal medulla

Main physiologic source of epi and norepi

158

What is a pheochromocytoma?

Tumor of the chromaffin cells that leads to excess epi and NE production

159

What is the classic gross findings of a pheochromocytoma? Why?

-Brown tumor of the adrenal glands
-Adrenal medulla is normally brown, but huge size of it

160

What are the clinical features of a pheochromocytoma?

-Episodic HTN
-HA
-Palpitations
-Tachycardia
-Sweating

161

How do you diagnose a pheochromocytoma?

Increase serum metanephrines and increased urine metanephrines and VMA

162

What is the treatment for a pheochromocytoma?

Surgical excision

163

What are the breakdown products of epi and norepi? What is the next step (enzyme and product) for each of these?

Metanephrine and normetanephrine respectively

Both converted to VMA by MAO

164

What is the MOA of phenoxybenzamine? Use?

Irreversible blocker of alpha receptors used in the treatment of a pheochromocytoma

165

Why is phenoxybenzamine given to patients prior to surgical excision of a pheochromocytoma?

If surgeon squeezes on the tumor, then will release a lot of epi/NE. This counteracts that

166

What are the four "rules of 10" for pheochromocytomas?

-10% are bilateral
-10% familial
-10% malignant
-10% located outside of the adrenal medulla

167

What is the classic exogenous location of a pheochromocytoma? S/sx of this?

Bladder wall

Urination causes HTN, HA, etc

168

If urination causes HTN, HA, etc, what should you suspect?

Pheochromocytoma of the bladder

169

What are the four genetic disorders that are associated with pheochromocytomas?

-MEN2A and MEN 2B
-VHL disease
-NF type 1

170

What is the gene that is the cause of MEN?

RET mutation

171

What is VHL disease?

Loss of the VHL suppressor gene