15. Endocrine Pathology Flashcards
(126 cards)
1
Q
what is a good way to think of the pancreas?
A
can think of it as 2 organs in 1:
- exocrine pancreas (digestive enzymes to GI tract)
- endocrine pancreas (subject of this section)
2
Q
what are the major functional cells in the endocrine pancreas?
A
cell clusters - islets of Langerhans
3
Q
what does a single islet cluster contain?
A
multiple cell types, each producing one type of hormone
alpha -> glucagon
beta -> insulin
delta -> somatostatin
4
Q
what is secreted by beta-cells?
A
insulin
5
Q
beta cells: where are they located in relation to the islets?
A
center
6
Q
what is the main function of insulin? what tissues does it most affect?
A
major anabolic hormone.
upregulates GLUT4 on skel muscle and fat tissue
7
Q
what is the result of increased GLUT4 receptors on skel muscle and fat tissue?
A
increased glucose uptake by tissues.
increased glycogen synthesis, protein synthesis, lipogenesis
8
Q
what do alpha cells secrete?
A
glucagon
9
Q
what does glucagon do?
A
opposes insulin in order to increase blood glucose levels via glycogenolysis and lipolysis
10
Q
is glucagon most active in fed or fasting state?
A
fasting state
11
Q
Type I DM: what is the main characteristic?
A
insulin deficiency leads to a metabolic disorder characterized by hyperglycemia
12
Q
what causes the destruction of beta cells in Type I DM?
A
autoimmune destruction of beta cells by T lymphocytes
Type 4 hypersensitivity reaction.
13
Q
which HLAs are associated with Type I DM destruction of beta cells?
A
HLA-DR3 and HLA-DR4
14
Q
at what life stage does Type 1 DM present?
A
childhood
15
Q
treatment for Type I DM?
A
lifelong insulin
16
Q
why is there high serum glucose in Type I DM?
A
lack of insulin leads to decr glucose uptake by fat and skel muscle
17
Q
what will be some qualities of the urine in a pt with Type I DM?
A
polyuria, glycosuria.
(hyperglycemia exceeds renal ability to resorb glucose; excess filtered glucose leads to osmotic diuresis)
18
Q
what happens to body weight and muscle mass of a pt with (untreated) Type I DM? what accounts for these?
A
weight loss, low muscle mass.
due to unopposed glucagon which leads to gluconeogenesis, breakdown of glycogen, breakdown of fat.
19
Q
what condition are people with Type I DM at risk for?
A
diabetic ketoacidosis
20
Q
what is the primary characteristic of diabetic ketoacidosis? (lab finding)
A
excessive serum ketones
21
Q
how can stress/infection lead to a state of diabetic ketoacidosis?
A
stress leads to increased epinephrine, which leads to increased glucagon, which increases lipolysis. Also increase in cortisol.
–> relative lack of insulin compared to quantities of counter-reg hormones. this increases FFAs which can be converted to ketone bodies in the liver
22
Q
what are Kussmaul respirations?
A
type of hyperventilation: deep/labored breathing, seen in T1DM, attempt to reduce acidosis by breathing out volatile acid (Co2)
23
Q
what are 3 lab abnormalities that result from diabetic ketoacidosis?
A
- hyperglycemia (>300 mg/dL)
- anion gap metabolic acidosis
- hyperkalemia
24
Q
what does insulin do to serum potassium levels? what happens to K in the absence of insulin? what will happen in diabetic ketoacidosis?
A
drives K into cells
without insulin the serum potassium will be high.
DKA: the H+/K+ exchanger brings H+ into cells and K+ into serum -> hyperkalemia
25
what is the status of potassium in diabetic ketoacidosis (high/low)?
has been driven out of cells by H+/K+ exchanger, so serum K+ levels are high.
but OVERALL BODY potassium will be LOW because the K+ is excreted via urine.
26
what is the clinical presentation of diabetic ketoacidosis?
Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, fruity breath (acetone)
27
treatment of diabetic ketoacidosis?
fluids (correcting polyuria-induced dehydration)
insulin
replacement of electrolytes (K+)
28
Type 2 DM: what is the fundamental problem?
end-organ insulin RESISTANCE leading to metabolic disorder characterized by hyperglycemia
29
what is the most common type of diabetes in US?
Type 2. 5-10% of US population, incidence is rising
30
Type 2 DM: onset?
middle-aged, obese adults
31
how does obesity lead to Type 2 DM?
leads to decr numbers of insulin receptors on muscle and adipose tissue
32
Type 2 DM vs Type 1: genetic predisposition is higher for which?
T2 stronger than for Type 1 DM
33
Type 2 DM: what happens to insulin levels over the course of the disease?
initially insulin levels increase, but later in the disease insulin deficiency develops due to beta cell exhaustion.
34
Type 2 DM: on pathology, what is found in the islets?
amyloid deposition
35
Type 2 DM: clinical presentation?
polyuria, polydipsia, hyperglycemia. but disease may be clinically silent
36
Type 2 DM: how is diagnosis made?
by measuring glucose levels: random, fasting, or glucose tolerance test
37
if doing a random glucose test, what level will dx Type 2 DM?
\> 200
38
if doing a fasting glucose test, what level will dx Type 2 DM?
\>126
39
if doing a glucose tolerance test, what level will dx Type 2 DM?
\> 200, 2 hrs after glucose loading
40
Type 2 DM: treatment?
- weight loss
- drug therapy to counter insulin resistance
- exogenous insulin due to beta cell exhaustion
41
Type 2 DM: pts are particularly at risk for what condition?
HONK: hyperosmolar non-ketotic coma
42
describe HONK
high glucose (\>500) leads to life threatening diuresis with hypotension and coma
43
HONK: will this be accompanied by diabetic ketoacidosis?
no: ketones are absent in this condition, because there are small amounts of circulating insulin. just enough to counter glucagon and avoid ketone generation
44
define pituitary adenoma. functional or non-functional?
benign tumor of anterior pituitary cells
can be functional or non functional
45
what is the biggest problem with non-functional pituitary adenomas?
mass effect: bitemporal hemianopsia due to compression of the optic chiasm
headache, hypopituitarism due to compression of the normal pit tissue
46
what are the most likely types of functional pituitary adenomas?
-prolactinomas & growth hormone adenomas
47
prolactinomas: how do they present in males? females?
males: decr libido
females: amenorrhea, galactorrhea
48
why does a prolactinoma cause anemmorrhea, galactorrhea (females), decr libido (males)?
prolactin prevents synthesis and release of GnRH, which causes release of FSH/LH
49
treatment for prolactinoma?
dopamine agonists (bromocriptine) to suppress prolactin production
50
growth hormone adenoma of pituitary: how will it present in children?
gigantism if it presents before closure of the epiphyseal plates
51
growth hormone adenoma of pituitary: presentation in adults?
acromegaly
52
signs of acromegaly?
enlarged jaw, frontal bossing, enlarged tongue
growth of visceral organs may lead to cardiac failure
53
given high levels of GH, what can a growth hormone adenoma cause?
secondary diabetes due to counter-reg hormone effect of GH
54
how to dx a growth hormone adenoma by simple blood test?
elevated GH, elevated IGF-1
55
how to dx growth hormone adenoma by stimulus test?
glucose bolus: should cause GH suppression.
If GH is not suppressed, probably overproduction
56
pharm treatment for GH adenoma?
octreotide: somatostatin analog, suppresses GH
57
ACTH adenomas secrete what, leading to what syndrome?
secrete ACTH, leading to Cushing Sx
58
causes of hypopituitarism?
- pituitary adenomas
- craniopharyngioma (kids)
- Sheehan sx (preg women)
- empty sella sx
59
how do pituitary adenomas or craniopharyngiomas lead to hypopituitarism?
mass effect, compression of normal tissue, or bleeding into gland
60
pathophys of Sheehan syndrome?
pregnancy-related infarction of the pituitary. gland normally doubles during preg, and its blood supply doesn't increase very much. if blood is lost during delivery, may become ischemic and infarct.
61
presentation of Sheehan syndrome?
poor lactation, loss of pubic hair (bc this is androgen-dependent)
62
What is Empty Sella syndrome?
Congenital defect of the sella: herniation of the arachnoid and CSF into the sella. Compresses/destroys pituitary. Pituitary = absent on imaging. FA: May be due to idiopathic atrophy of pituitary, common in obese women.
63
what 2 hormones are made in the hypothal, then released from the posterior pit?
ADH, oxytocin
64
ADH does what?
acts on distal tubules and collecting ducts of kidney, promotes free water retention
65
oxytocin does what?
mediates uterine contraction during labor, mediates release of breast milk during lactation
66
Central Diabetes Insipidus: deficiency of what?
ADH
67
reasons for central diabetes insipidus?
- hypothalamic pathology
- pituitary pathology: tumor, trauma, infection
68
Central DI: serum and urine status?
Serum: concentrated, hypernatremic
Urine: dilute, low specific gravity
69
central DI: why hypernatremia?
due to loss of free water due to lack of ADH
70
how to test for central DI?
water deprivation test. if central DI, patient will fail to concentrate urine as they should
71
how to treat central DI?
desmopressin (ADH analog)
72
Nephrogenic DI: define
impaired renal response to ADH
73
Nephrogenic DI: response to desmopressin
none, because problem is non-response to ADH
74
Nephrogenic DI: causes?
inherited mutations
drugs (lithium, demeclocycline = ADH inhibitor, treatment for SIADH)
75
SIADH: define
inappropriate ADH secretion
76
SIADH: cause?
ectopic production of ADH due to small cell carcinoma;
CNS trauma
pulm infection
some drugs
77
SIADH: symptoms?
excessive retention of free water. hyponatremia and low serum osmolality.
mental status changes due to neuronal swelling from hyponatremia
78
SIADH: treatment
water restriction
demeclocycline (blocks effect of ADH, caution: can cause Nephrogenic DI)
79
what is non-enzymatic glycosylation?
sugar sticks to basement membranes of vasculature, no enzymes required.
80
what does NEG of large and medium sized vessels lead to?
atherosclerosis
81
what are some of the leading causes of complications in diabetics?
- cardiovascular disease
- peripheral vascular disease (leading cause of non traumatic amputations)
82
NEG of small vessels leads to what?
hyaline arteriosclerosis (thickened vessel membrane, decr size of lumen)
83
NEG of renal arterioles leads to what?
glomerulosclerosis --\> small, scarred kidneys with granular surface
84
NEG preferentially involves which renal arterioles?
efferent; leading to glomerular hyperfiltration injury with microalbuminemia.
85
what will glomerular hyperfiltration injury with microalbuminenia eventually lead to?
nephrotic syndrome, with K-W nodules in glomeruli
86
what is pathongmonic of diabetic nephropathy?
Kimmelstiel-Wilson nodules in glomeruli
87
what causes HbA1c?
HbA1c = glycated hemoglobin
caused by NEG of red blood cells
88
how can high serum glucose can cause damage to retinal vessels and schwann cells?
via osmotic damage: retinal blood vessel pericytes freely take in glucose, which is converted to sorbitol; osmolarity increases, water comes into cells and weakens vessel wall -\> rupture and micro hemorrhage Similar for schwann cells -\> peripheral neuropathy
89
in general, what kinds of problems does osmotic damage due to high serum glucose lead to?
- peripheral neuropathy
- impotence
- blindness
- cataracts
90
what is MEN1? what does it present with?
Multiple Endocrine Neoplasia (genetic)
Presents with pancreatic neoplasms, parathyroid hyperplasia, pituitary adenomas (3 Ps)
91
Insulinoma: presentation?
epidosic hypoglycemia with mental status changes that can be relieved with administration of glucose
92
how do we dx an insulinoma?
low serum glucose levels, high insulin, high C-peptide
93
besides an insulinoma, what are the other two types of pancreatic tumors?
gastrinoma
somatostatinoma (delta cells in islets)
94
gastrinoma: from what organ? presentation?
Pancreas.
presents as treatment-resistant peptic ulcers. may be multiple ulcers, may extend into jejunum. Called Zollinger-Ellison syndrome
95
somatostatinoma: from what organ? presentation?
Pancreas.
presents as achlorhydria (?due to inhibition of gastrin) and chloelithiasis with steatorrhea (due to inhibition of CCK from gallbladder)
96
what cells regulate Ca? how do they do this?
chief cells in the parathyroid gland. they secrete PTH
97
Chief cells regulate what type of Ca in the blood?
free/ionized, as opposed to Ca that is bound to proteins
98
if serum Ca is low, what are the 3 actions of PTH?
1. Bone: incr. osteoclast activity, releasing Ca and phosphate
2. GI: incr absorption of Ca and P
3. Kidney: incr Ca reabsorption; decr phosphate reab
99
how does PTH cause an incr in GI reab of C and P?
by activating Vit D
100
how does PTH cause an incr in bone osteoclast activity?
by activating osteoblasts, which then activate osteoclasts
101
PTH: what is the neg feedback for its secretion?
increased serum ionized Ca levels
102
what are the most common causes of Primary HyperPTH?
- parathyroid adenoma
- sporadic parathyroid hyperplasia
- parathyroid carcinoma
103
parathyroid adenoma: benign or malig? what does it secrete?
benign, secretes PTH
104
parathyroid adenoma most commonly causes what?
asymptomatic hypercalcemia
105
parathyroid adenoma and incr PTH may cause what? (6 items)
- hypercalcemia
- nephrolithiasis
- nephrocalcinosis
- CNS disturbances
- acute pancreatitis
- osteitis fibrosa cystica
106
what causes nephrolithiasis?
kidney stones made of calcium oxalate, due to high serum Ca
107
what is nephrocalcinosis? what can it cause?
metastatic calcification of renal tubules; deposition of Ca on tissues. can cause renal insufficiency and polyuria
108
how can hyperPTH cause acute pancreatitis?
high Ca, think of Ca as sort of an enzyme activator that will activate the cells of the pancreas. Not accurate but a way to remember.
109
what is osteitis fibrous cystic?
resorption of bone, leading to fibrosis and cystic spaces. due to hyperPTH
110
hyperPTH: what are lab findings? (5)
incr serum PTH
incr serum Ca
decr serum phosphate
incr urinary cAMP
incr serum alkaline phosphatase
111
why does hyperPTH cause incr serum alkaline phosphatase?
this is a sign of osteoblast activity, and it creates an alkaline environment at the bone, which is needed to lay down Ca.
112
why does hyperPTH cause incr urinary cAMP?
PTH binds its receptor, which stimulates a G-coupled protein receptor pathway, upreg Adenylate Cyclase, ATP --\> cAMP.
when this process occurs in kidney cells, cAMP is increased in the urine
113
define secondary hyperparathyroidism
excess production of PTH due to a disease process extrinsic to the parathyroid gland
114
what is the most common cause of 2' hyperPTH?
chronic renal failure
115
how does chronic renal failure lead to 2' hyperPTH?
- renal insuff leads to decr phosphate excretion
- incr serum phosphate binds free calcium
- decr free calcium stimulates parathyroid glands
- incr PTH leads to bone resorption
116
lab findings in 2' hyperparathyroidism? (4)
incr PTH
decr serum Ca
incr serum P
incr alkaline phosphatase
117
what can lead to hypoPTH?
- autoimmune damage
- surgical excision
- DiGeorge syndrome
118
what is DiGeorge syndrome?
failure to develop the 3rd and 4th pharyngeal pouches, so failure to develop PTH glands.
119
hypoPTH: 2 symptoms?
- muscle spasms/tetany
- numbness/tingling, esp periorally
120
what are two tests for muscle spasms due to hypoPTH?
Trousseau: BP cuff, see if distal limb spasms
Chvostek: tap on facial nerve -\> spasm
121
hypoPTH: labs? (2)
decr PTH, decr Ca
122
what is pseudohypoPTH?
due to end organ resistance to PTH
123
pseudohypoPTH: lab findings? (2)
decr Ca, incr PTH
124
pseudohypoPTH: what does the auto dom form present with?
short stature short 4th/5th digits
125
pseudohypoPTH: what is mech for end organ resistance?
could be associated with a defect in the Gstim pathway
126
