Pathoma Chapter 15 - 2

Front 1

What are chief cells?

Back 1

they are cells of the parathyroid gland that regulate serum free calcium via PTH secretion

Front 2

What does PTH secretion do?

Back 2

+ increases bone osteoclast activity, releasing Ca and PO4
+ increasing small bowel absorption of Ca and PO4 (indirectly via Vit D)
+ increasing renal Ca++ reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)

Front 3

Describe the control of PTH secretion

Back 3

increased serum ionized Ca++ provides negative feedback to decrease PTH

Front 4

What is primary hyperparathyroidism and what are its causes?

Back 4

+ excess PTH due to a disorder of the parathyroid gland
+ causes: parathyroid adenoma, sporadic parathyroid hyperplasa and parathyroid carcinoma

Front 5

what are some of the features of a parathyroid adenoma?

Back 5

+ benign neoplasm, involving one gland
+ usually asymptomatic hypercalcemia
+ may present with consequence of increased PTH and hypercalcemia: nephrolithiasis, nephrocalcinosis, CNS disturbances, constipation, peptic ulcer disease, acute pancreatitis, osteitis fibrosa cystica (resorption of bone leading to fibrosis and cystic spaces)

Front 6

What are lab findings in primary hyperparathyroidism?

Back 6

increased serum PTH
increased serum Ca++
decreased serum PO4
increased urinary cAMP
increased serum alkaline phosphatase

Front 7

What is the treatment of primary hyperparathyroidism?

Back 7

surgical removal of affected gland

Front 8

what is secondary hyperparathyroidism?

Back 8

Excess production of PTH due to a disease process extrinsic to the parathyroid gland

Front 9

what are causes of secondary hyperparathyroidism?

Back 9

chronic renal failure --> decreased phosphate excretion --> increased serum phosphate --> binds free calcium --> dec. free calcium --> stimulates all four parathyroid glands --> bone resorption

Front 10

what are lab findings in secondary hyperparathyroidism?

Back 10

increased serum PTH
decreased serum Ca++
increased serum PO4
increased serum alkaline phosphatase

Front 11

what is hypoparathyroidism and what are the causes?

Back 11

+ low PTH
+ causes: AI damage to parathyroids, surgical excision and DiGeorge syndrome

Front 12

How does hypoparathyroid present?

Back 12

low serum calcium
numbness and tingling (particularly circumoral)
muscle spasms (tetany) - facial nerve tapping (Chvostek sign)

Front 13

What are lab findings in hypoparathyroidism?

Back 13

decreased PTH
decreased serum calcium

Front 14

What is the cause of pseudohypoparathyroidism?

Back 14

end-organ resistance to PTH
AD form associated with short stature and short 4th and 5th digits

Front 15

What do labs reveal in cases of pseudohypoparathyroidism?

Back 15

hypocalcemia with increased PTH

Front 16

What major hormones are produced by the endocrine pancreas and what part of the islet of langerhans do they come from?

Back 16

+ insulin - beta cells - center of islets
+ glucagon - alpha cells

Front 17

What are the effects of insulin?

Back 17

l. upregulates insulin-dependent glucose transporter protein (GLUT4) on skeletal muscle and adipose tissue (glucose uptake by GLUT4 decreases serum glucose)

2. Increased glucose uptake by tissues leads to increased glycogen synthesis, protein synthesis, and lipogenesis.

Front 18

What are the effects of glucagon?

Back 18

it opposes insulin in order to increase blood
glucose levels (e.g., in states of fasting) via glycogenolysis and lipolysis.

Front 19

What is type I diabetes mellitus?

Back 19

Insulin deficiency leading to a metabolic disorder characterized by hyperglycemia

Front 20

What is the cause of type I DM?

Back 20

Due to autoimmune destruction of beta cells by T lymphocytes
l. Characterized by inflammation of islets
2. Associated with HLA-DR3 and HLA-DR4
3. AutoAbs against insulin are often present (sign of damage) and may be seen years before clinical disease develops.

Front 21

What are the clinical manifestations of insulin deficiency?

Back 21

l. High serum glucose
2. Weight loss, low muscle mass, and polyphagia -
3. Polyuria, polydipsia, and glycosuria

Front 22

How does insulin deficiency lead to weight loss, low muscle mass and polyphagia?

Back 22

Unopposed glucagon leads to gluconeogenesis, glycogenolysis and lipolysis, which further exacerbates hyperglycemia.

Front 23

How does insulin deficiency lead to polyuria, polydipsia, and glycosuria?

Back 23

Hyperglycemia exceeds renal ability to resorb glucose; excess filtered glucose leads to osmotic diuresis.

Front 24

What is the treatment of diabetes mellitus type I?

Back 24

lifelong insulin

Front 25

What is diabetic ketoacidosis and its causes?

Back 25

it is a complication of diabetes that is characterized by excessive serum ketones

arises with stress (e.g., infection); epinephrine stimulates glucagon secretion increasing lipolysis (along with gluconeogenesis and glycogenolysis).
i. Increased lipolysis --> increased FFAs
ii. Liver converts FFAs to ketone bodies

Front 26

What are symptoms of diabetic ketoacidosis?

Back 26

+ hyperglycemia(> 300 mg/dL), anion gap metabolic acidosis, and hyperkalemia
+ presents with Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (due to acetone)

Front 27

What is the treatment for diabetic ketoacidosis?

Back 27

fluids (corrects dehydration from polyuria), insulin, and replacement of electrolytes (e.g., potassium)

Front 28

What is type II diabetes mellitus and who is at the greatest risk?

Back 28

End-organ insulin resistance leading to a metabolic disorder characterized by hyperglycemia

middle-aged, obese adults, especially those that have a genetic predisposition

Front 29

How are insulin levels affected by type II diabetes mellitus?

Back 29

Insulin levels are increased early in disease, but later, insulin deficiency develops due to beta cell exhaustion

Front 30

What does histology reveal in type II diabetes mellitus?

Back 30

amyloid deposition in the islets

Front 31

What are clinical features of type II diabetes mellitus?

Back 31

polyuria, polydipsia, and hyperglycemia, but disease is
often clinically silent.

Front 32

How do you diagnose type II diabetes mellitus?

Back 32

measuring glucose levels (normal is 70-120 mg/dL).
1. Random glucose > 200 mg/dL
2. Fasting glucose > 126 mg/dL
3. Glucose tolerance test with a serum glucose level > 200 mg/dL two hours after glucose loading

Front 33

What is the treatment of type II diabetes mellitus?

Back 33

weight loss (diet and exercise) initially; may require drug therapy
to counter insulin resistance (e.g., sulfonylureas or metformin) or exogenous insulin
after exhaustion of beta cells

Front 34

What is hyperosmolar-non-ketotic coma?

Back 34

a risk complication of type II diabetes in which high glucose(> 500 mg/dL) leads to life-threatening diuresis with hypotension and coma.

Ketones are absent due to small amounts of circulating insulin

Front 35

What are some long term consequences of diabetes?

Back 35

+ nonenzymatic glycosylation of vascular basement membrane
+ osmotic damage

Front 36

What does NEG of large and medium sized vessels lead to?

Back 36

atherosclerosis and its resultant complications; cardiovascular disease, peripheral vascular disease (nontraumatic amputations)

Front 37

What does NEG of small sized vessels lead to?

Back 37

hyaline arteriolosclerosis
i. Involvement of renal arterioles leads to glomerulosclerosis, resulting in small,
scarred kidneys with a granular surface
ii. Preferential involvement of efferent arterioles leads to glomerular hyperfiltration injury with microalbuminuria that eventually progresses
to nephrotic syndrome; characterized by Kimmelstiei-Wilson nodules in glomeruli

Front 38

What does NEG of hemoglobin lead to?

Back 38

glycated hemoglobin (HbA1c), which serves as a marker of glycemic control

Front 39

How does diabetes lead to osmotic damage and what are the resulting clinical manifestations?

Back 39

1. Glucose freely enters into Schwann cells (which myelinate peripheral nerves), pericytes of retinal blood vessels, and the lens.
2. Aldose reductase converts glucose to sorbitol, resulting in osmotic damage.
3. Leads to peripheral neuropathy, impotence, blindness, and cataracts

Front 40

What diseases is MEN1 associated with?

Back 40

pancreatic endocrine neoplasms
parathyroid hyperplasia
pituitary adenomas

Front 41

How do insulinomas present?

Back 41

episodic hypoglycemia with mental status changes that are relieved by administration of glucose.

Front 42

How are insulinomas diagnosed?

Back 42

decreased serum glucose (<50 mg/dL), increased insulin and increased C-peptide

Front 43

How do gastrinomas present?

Back 43

treatment-resistant peptic ulcers (Zollinger-Ellison
syndrome); ulcers may be multiple and can extend into the jejunum

Front 44

How do somatostatinomas present?

Back 44

achlorhydria (due to inhibition of gastrin) and
cholelithiasis with steatorrhea (due to inhibition of cholecystokinin).

Front 45

How do VIPomas present?

Back 45

secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria

Front 46

What are the layers of the adrenal cortex and what hormones associated with each layer?

Back 46

1. Glomerulosa produces mineralocorticoids (e.g., aldosterone).
2. Fasciculata produces glucocorticoids (e.g. cortisol).
3. Reticularis produces sex steroids (e.g. testosterone).

Front 47

What is cushing syndrome and what are the clinical features?

Back 47

A. Hypercortisolism
B. Clinical features:
1. Muscle weakness with thin extremities
2. Moon facies, buffalo hump, and truncal obesity
3. Abdominal striae
4. Hypertension
5. Osteoporosis
6. Immune suppression

Front 48

How does Cushing syndrome lead to muscle weakness?

Back 48

Cortisol breaks down muscle for gluconeogenesis.

Front 49

How does Cushing syndrome lead to truncal obesity?

Back 49

High insulin (due to high glucose) increases storage of fat.

Front 50

How does Cushing syndrome lead to abdominal striae?

Back 50

Due to impaired synthesis of collagen with thinning of skin

Front 51

How do you diagnose Cushing's syndrome?

Back 51

increased 24-hour urine cortisol levels

Front 52

What are the causes of Cushing's syndrome?

Back 52

l. Exogenous corticosteroids
2. Primary adrenal adenoma, hyperplasia, or carcinoma
3. ACTH-secreting pituitary adenoma
4. Para neoplastic ACTH secretion (e.g., small cell carcinoma of the lung)

Front 53

What are the consequences of exogenous corticosteroids?

Back 53

Bilateral adrenal atrophy; steroids suppress
ACTH secretion (negative feedback).

Front 54

What are the consequences of primary adrenal adenoma, hyperplasia, or carcinoma

Back 54

leads to atrophy of the uninvolved adrenal gland

Front 55

What are the consequences of ACTH-secreting pituitary adenoma?

Back 55

leads to bilateral adrenal hyperplasia

Front 56

What are the consequences of para neoplastic ACTH secretion

Back 56

leads to bilateral adrenal hyperplasia

Front 57

How does dexamethasone work?

Back 57

High-dose dexamethasone (cortisol analog) suppresses ACTH production by a pituitary adenoma (cortisol levels decrease), but fails to suppress ectopic ACTH production by a small cell lung carcinoma (cortisol levels remain high).

Front 58

What is Conn's syndrome and how does it present?

Back 58

A. Excess aldosterone
B. Presents as hypertension with hypernatremia, hypokalemia, and metabolic alkalosis

Front 59

How does aldosterone lead to hypertension?

Back 59

l. Aldosterone increases sodium absorption and secretion of potassium and hydrogen ions (distal tubules and collecting duct).
2. Increased absorption of sodium expands plasma volume leading to hypertension.

Front 60

What is the cause of primary hyperaldosteronism?

Back 60

adrenal adenoma;
sporadic adrenal hyperplasia and adrenal carcinoma are less common causes.

Front 61

How do primary and secondary hyperaldosteronism compare in levels of aldosterone and renin?

Back 61

primary: high aldosterone and low renin (high blood pressure downregulates renin via negative feedback)
secondary: high aldosterone and high renin

Front 62

What is the cause of secondary hyperaldosteronism?

Back 62

activation of the renin-angiotensin system (e.g., renovascular hypertension or CHF)

Front 63

What is congenital adrenal hyperplasia and what are its causes?

Back 63

Excess sex steroids with hyperplasia of both adrenal glands
Causes: Inherited 21-hydroxylase deficiency

Front 64

How does 21-hydroxylase deficiency leading to congenital adrenal hyperplasia?

Back 64

1. 21-hydroxylase is required for the production of aldosterone and corticosteroids.
2. In enzyme deficiency, steroidogenesis is predominantly shunted toward sex
steroid production (which does not require 21-hydroxylase).
3. Deficiency of cortisol leads to increased ACTH secretion (lack of negative feedback), which results in bilateral adrenal hyperplasia.

Front 65

What are clinical features of congenital adrenal hyperplasia?

Back 65

Salt wasting with hyponatremia, hyperkalemia, and hypovolemia due to lack of aldosterone.
2. Life-threatening hypotension due to lack of cortisol.
3. Clitoral enlargement (females) or precocious puberty (males) due to excess androgens

Front 66

What is adrenal insufficiency and what are its causes?

Back 66

A. Lack of adrenal hormones
B. Acute insufficiency may arise with Waterhouse-Friderichsen syndrome.
C. Chronic insufficiency (Addison disease) is due to progressive destruction of the adrenal glands.

Front 67

What are the clinical manifestations of Waterhouse-Friderichsen syndrome?

Back 67

l. Characterized by hemorrhagic necrosis of the adrenal glands classically due to DIC in young children with N meningitidis infection
2. Lack of cortisol exacerbates hypotension, often leading to death

Front 68

What are the causes of progressive destruction of adrenal glands?

Back 68

autoimmune destruction (most common cause in
the West), TB (most common cause in the developing world), and metastatic carcinoma (e.g., arising from lung).

Front 69

What are clinical features of Addison's disease?

Back 69

hypotension, hyponatremia, hypovolemia,
hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, and diarrhea.

Front 70

What cells make of the adrenal medulla and what hormones are produced?

Back 70

A. Composed of neural crest-derived chromaffin cells
B. Main physiologic source of catecholamines (epinephrine and norepinephrine)

Front 71

What is pheochromocytoma?

Back 71

Tumor of chromaffin cells

Front 72

What are the clinical features of pheochromocytoma?

Back 72

clinical features are due to increased serum catecholamines.
l. Episodic hypertension, headache, palpitations, tachycardia, and sweating

Front 73

How do you diagnose pheochromocytoma?

Back 73

Increased serum metanephrines and increased 24-hour urine metanephrines and vanillylmandelic acid

Front 74

How do you treat pheochromocytoma?

Back 74

Surgical excision
l. Catecholamines may leak into the bloodstream upon manipulation of the tumor.
2. Phenoxybenzamine (irreversible a-blocker) is administered perioperatively to prevent a hypertensive crisis.

Front 75

What is the rule of 10s in the presentation of pheochromocytoma?

Back 75

10% bilateral, 10% familial, 10% malignant, and 10% located outside of the adrenal medulla (e.g., bladder wall or organ of Zuckerkandl at the inferior mesenteric artery root)

Front 76

What is pheochromocytoma associated with?

Back 76

MEN 2A and 2B, von Hippel-Lindau disease, and neurofibromatosis type 1