Things I don't know: PathoPhys Flashcards
1
Q
What should you do before giving TH in SEVERE hypothyroidism?
A
replace corticosteroids
2
Q
Sx of thyrotoxic crisis
A
SOB, tachycardia, afib, vomit, diarrhea, jaundice, lost lots of weight
hyperthyroid that DIDN’T TAKE THYROID MEDS
3
Q
Tx of thyroid storm
A
TREAT NOW
life threatening issues first: intubation, diuresis, anti-seizure meds
then: thionamide, iodine (stops them from making thyroid), gluccocorticoids, bile acid binder, nutrition
get free T3 to guide therapy
4
Q
Mechanisms of damage in high glucose
A
- polyol pathway: sorbitol
- AGE formation (advanced glycation end product): ROS production
- PKC activation
- increased hexosamines
- PARP (poly ADP ribose polymerase)
- epigenetic (methylation/demethylation)
5
Q
Who is at an increased risk of diabetic nephropathy? Most sensitive test?
A
increased urine albumin excretion
if untreated leads to end stage renal disease
maintain normal UAE: no nephropathy
6
Q
How does insulin Tx affect someone with increased GFR and UAE?
A
UAE: returns to normal in T1DM, and many in T2DM return to normal
GFR: may remain elevated in both
7
Q
What almost always accompanies proteinuria?
A
increase in BP
8
Q
How long does it take micro-albuminuria to develop in T1DM?
A
5-15 yrs
9
Q
What increases likelihood of lower limb amputation in diabetic?
A
symptoms of peripheral neuropathy
10
Q
positive symptoms of diabetic peripheral neuropathy
A
pain, paresthesia, dysesthesia, allodynia
11
Q
negative symptoms of diabetic peripheral neuropathy
A
decrease sensation to temp., pain, touch, motor movement
12
Q
clinical staging of diabetic nephropathy
A
- nonproliferative diabetic retinopathy (NPDR): asymptomatic
- preproliferative diabetic retinopathy: laser therapy can prevent vision loss
- proliferative diabetic retinopathy (PDR): major cause of vision loss
13
Q
epsilon cell of pancreas
A
secrete ghrelin
14
Q
gamma cell
A
PP cell
secretes pancreatic peptide
15
Q
Fn3K
A
deglycation of RBC
16
Q
What causes the islet damage in DM?
A
islet specific T cells
Ab: GAD, ICA, IAA, ZnT8
17
Q
HLA DR2/DR2
A
protective against T1DM
18
Q
DQ beta chain
A
neg: susceptible to T1DM
pos: protection from T1DM
can be in middle
DR4/DR4 overrides protection
19
Q
DQ7
A
primary protection against T1DM
20
Q
DQ8
A
primary susceptibility to T1DM
21
Q
amylin
A
B cells of pancreas
decrease gastric emptying
decrease glucagon secretion
promotes satiety
22
Q
GLP-1
A
increase insulin secretion
decrease glucagon and gastric emptying
23
Q
What can cause mental status change in SIADH?
A
brain swells
can also cause seizures
24
Q
What osmotic factors can stimulate ADH?
A
Na, mannitol, urea
NOT: glucose
25
What are the non-osmotic factors than stimulate ADH?
```
hypotension, hypovolemia
N/V
hypoglycemia
renin-angiotensin
Pain, stress, emotion?
```
26
Factors that alter AQP2 levels
1. increase
2. decrease
1. CHF, pregnancy, SIADH
| 2. DI, postobstructive polyuria, chronic renal failure
27
Normal serum Na
136-145 mEq/L
28
What is renal tubular Na reabsorption regulated by?
1. SGLT
2. ANP
3. Renin-angiotensin-aldosterone
29
causes of hyponatremia
1. hypovolemic
2. hypervolemic
3. euvolemic
1. high urine output and Na excretion, increase ANP
2. edema (nephrotic syndrome, CHF, cirrhosis), water intoxication
3. ADH mediated water retention
30
clinical presentation of hyponatremia
1. early
2. later
3. chronic
1. N/V, headache
2. seizure, coma, resp. arrest
3. lethargy, confusion, muscle cramps, neuro impairment
31
causes of SIADH
```
paraneoplastic
trauma
CVA
infection: pulmonary, brain, near
drugs: cancer, psych
```
32
Tx SIADH
FLUID RESTRICTION
| demeclocycline, lithium, vaptans
33
hypernatremia Sx
thirst, lethargy, irritable, seizure, fever, oliguria
34
Causes of hypernatremia
1. DI
2. Na excess
3. water depletion exceeding Na depletion: diarrhea, vomit, dehydration
4. drugs: lithium, cyclophosphamide, cisplatin
35
DIDMOAD syndrome
familial
central DI
DM, nerve deafness, optic atrophy, bladder and ureter atonia
36
water deprivation test
1. Uosm after vasopressin increases 50%
2. less than 50%
1. central DI
| 2. nephrogenic DI or psychogenic
37
familial hypocalciuric hypercalcemia
```
AD inactivating mutation in CaSR
mildly increased serum Ca and PTH
asymptomatic
low urine Ca (unlike primary hyperparathyroidism)
Tx: no intervention
```
38
drugs that induce hypercalcemia
lithium
| HCTZ
39
PTH independent hypercalcemia
1. tumor: PTHrP or bone metastases
2. granulomatous disease (TB, sarcoidosis, lymphoma): increase vit. D
3. multiple myeloma
4. hyperthyroidism, adrenal failure
5. immobilization
6. medications: Vit. D, Vit. A, milk-alkali syndrome
40
primary hyperparathyroidism work up
1. Ca, albumin
2. PTH
3. 25-OH vit. D
4. 24 hour urine Ca (to differentiate from FHH)
5. imaging: thyroid US (localize), 99Tc-sestamibi scan (localize), DXA
41
criteria that indicates parathyroidectomy
1. Ca above 1 mg/dL above UNL
2. less than 50 yrs old
3. osteoporosis
4. renal insufficiency
42
nonsurgical Tx for hyperparathyroidism
hydrate
bisphosphonates
Vit. D maintenance
cinacalcet
43
if hypercalcemia is due to malignancy, what will PTH be
suppressed
| breast and squamous cell CA most common
44
What causes hypercalcemia in malignancy?
PTHrP
bony metastasis
cytokines activating osteoclasts
multiple myeloma: destroys bone
45
how do granulomatous disease cause hypercalcemia
increase 1 alpha hydroxylase which increases Vit. D
increase Ca, PO4
decrease PTH
46
tx of acute hypercalcemia
FIRST: address volume status: saline if dehydrated
then:
1. saline diuresis and furosemide: blocks Na/K ATPase causing Ca secretion
2. calcitonin (3rd line)
3. bisphosphonates
4. glucocorticoids (in myeloma, granulomatous disease, Vit. D toxicity)
5. dialysis
47
Work up for secondary hyperparathyroidism
Sx most likely due to underlying disease not PTH
serum PTH, Ca (with albumin), P, creatinine, Vit. D
do NOT need 24 hour urine Ca
no image studies if Ca normal
Tx underlying disease
48
weird causes of hypocalcemia
1. acute pancreatitis: free FA chelate Ca
2. massive transfusion: citrate binds Ca
3. tumor lysis syndrome or rhabdomyolysis: Pi released binds Ca
4. meds: Pi, bisphosphonates
5. hungry bone syndrome
49
Sx of hypocalcemia
```
agitation
HYPERREFLEXIA
convulsions
HTN
long QT
```
50
Work up of hypocalcemia
what does low PTH indicate?
high PTH?
albumin, total Ca x 2, PTH
low PTH: Mg deficiency, phosphate excess, hypoparathyroid
high PTH: severe vitamin D deficiency, renal failure, PTH or Vit. D resistance
51
pseudohypoparathyroidism
mutation in Gs alpha subunit
PTH resistance
hypocalcemia, hyperphosphatemia, high PTH
short stature, round face, short 4th metacarpal, obesity, Albright's hereditary osteodystrophy
52
acute hypocalcemia crisis Tx
ALWAYS correct MAGNESIUM if low
| Ca gluconate
53
long term hypocalcemia Tx
1. Ca
2. Vit. D (need active form unless PTH is present)
3. Hydrochlorothiazide: increase renal reabsorption of Ca in distal tubule
54
hyperglycemic crises pathogenesis
insulin deficiency: increased glucose production, decreased glucose uptake
increases glucagon, GH, cortisol, catecholamines
hyperglycemia leading to osmotic diuresis leading to volume depletion
55
ketoacidosis
adipose: FA release
liver: increased ketogenesis
leads to ketoacidosis leading to decreased alkali reserve leading to metabolic acidosis
also get hyperglycemia leading to osmotic diuresis leading volume depletion
56
Dx of DKA
```
plasma glucose greater than 250
LOW pH (less than 7.3)
LOW bicarb: less than 18
ketones: POSITIVE
Sx of drowsy only in moderate
Sx of stupor/coma: only in severe
```
57
Dx of HHS (hyperglycemic crises)
```
pH greater than 7.3: NORMAL
bicarb greater than 18: NORMAL
anion gap is HIGH
serum osmol greater than 330
plasma glucose greater than 800
drowsy, stupor, coma
ketones: can be positive
```
58
Causes of DKA and HHS
new DM
failure to take insulin
infection or medical illness
59
presentation of DKA
polydipsia, polyuria, weak, hypothermia, tachycardia, altered sensorium
unique: WEIGHT LOSS, abdominal pain, ILEUS, N/V, tachypnea, KUSSMAUL breathing, ACETONE breath
SHORT ONSET
60
presentation of HHS
polydipsia, polyuria, weak, hypothermia, tachycardia, altered sensorium
unique: Sx of accompanying illness, poor appetite, MENTAL STATUS CHANGE, HYPOTENSION
LONG ONSET
61
lab studies for HHS and DKA
immediate: blood glucose and serum ketones
also: ABG, CBC, CMP, ketones, urinalysis
CMP: glucose, electrolytes, bicarbonate, PO4, Mg, BUN, creatinine
62
anion gap
AG = Na - (Cl + HCO3)
63
serum osmolarity
2Na + glucose/18 + BUN/2.8
64
Tx in
1. DKA
2. HHS
DKA: lots of INSULIN (titrated to avoid hypoglycemia), normal saline, then hypotonic
2. some insulin, LOTS of fluid: normal saline, then hypotonic
do NOT give insulin until K is corrected
65
corrected Na
(1.6 x glucose -100)/ 100
66
DKA serum
1. Na
2. K
1. hyponatremia
| 2. hyperkalemia
67
markers for bone formation
ALP
osteocalcin
carboxyterminal propeptide of type 1 collagen (P1NP)
68
markers for bone resorption
N-telopeptide
| carboxyterminal of type 1 collagen (CTX-1)
69
DXA
gold standard to measure bone mineral density (important predictor of fractures)
70
clinical evaluation of osteoporosis
Ca, PO4, inactive (25) Vit. D, DXA
71
T score of osteoporosis Dx
less than -2.5
| or LOW TRAUMA fracture and greater than -2.5
72
meds that increase fracture risk
glucocorticoids, TCA, benzodiazepines, antipsychotics, PPIs, SSRIs, anticonvulsants, aromatase inhibitors, androgen deprivation therapy
73
fracture risks
```
femoral neck T score
age
previous low trauma fracture
low BMI
smoking
steroids
RA
High alcohol use
family Hx
```
74
endocrine mediated causes of low bone mass density
```
cushing's
hypercalcemia, kidney stones
acromegaly
hypogonadism
hyperthyroidism
```
75
Tx of osteoprosis
stop smoking/drinking
increase exercise
Ca, Vit. D
fall prevention
76
Osteoporosis: who do you give meds
1. T score less than -2.5 after age 50
2. osteopenia with Hx of fragility fracture
3. use FRAX score for under 50 and T score less than -2.5 or older than 50 with greater than -2.5
77
inherited Ricket's
AR
low Vit. D: 1 alpha hydroxyls deficiency
high Vit. D: receptor defect
78
Bone pain
fibrous dysplasia
osteitis fibrosa cystica
osteogenesis imperfecta
Paget's
79
McCune-Albright
```
GNAS1 gene mutation
precocious puberty
fibrous dysplasia
cafe au lait
hypophosphatemia due to FGF-23
```
80
corrected Ca (when albumin is low)
(0.8 x (4 - patient's albumin) + serum Ca
81
most common cause of acromegaly
pituitary MACROadenoma
82
What are GH levels after oGTT?
normal
acromegaly
normal: less than 1 ng/ml
acro: greater than 2 ng/ml
83
acromegaly Sx
```
large hands, feet
maxillofacial change
arthralgia
excess sweating
headache
hypogonadal
sleep apnea
HTN
DM
```
84
Prolactin levels
1. normal
2. prolactinoma
3. macroprolactinoma
1. lower than 25 ug/l
2. greater than 250
3. greater than 500
85
drugs that cause high prolactin
antipsychotics: DA antagonist
| reserpine, haloperidol
86
labs for TSH secreting pituitary adenoma
RARE
high T4 and TSH
confirm with MRI
87
What should you give to a patient that has central (pituitary) hypothyroidism along with levothyroxine?
why?
glucocorticoids
TH replacement therapy causes accelerated metabolism of endogenous cortisol causing adrenal insufficiency
need to evaluate adrenal reserve
88
commonly one of the first derangements of cushings
failure to achieve normal late night (11pm to 1am low cortisol) circadian nadir
89
Dx of cushing
1. 24 hour urine free cortisol
2. late night salivary cortisol
3. 1 mg overnight dexamethaonse suppression test (give 1 mg at 11pm-12am and measure at 8am)
4. longer low dose DST (2 day, 2 mg dose every 6 hours for 8 doses; check 2 or 6 hours after last dose)
90
Who gets false positives for overnight dexamethasone suppression test?
why?
women on oral contraceptives
| increase CBG, but measure total cortisol rather than free
91
what should cortisol be in dexamethasone suppression test
normal: less than 1.8 mug/dl
92
what should you suspect in a patient with acute unexplained volume depletion and shock
acute adrenal insufficiency
| hyperkalemia, acidosis, hypoglycemia
93
Dx of adrenal insufficiency
ACTH stimulation test
94
mutation in CYP21A2 gene
21-hydroxylase deficiency
| can't convert 17-hydroxyprogesterone to 11-deoxycortisol
95
congenital adrenal hyperplasia: 21-hydroxylase deficiency: girl presentation
salt losing and non-salt losing
NEONATE presentation
ambiguous genitalia, clitoral enlargement, common urethral-vaginal orifice, partial or complete fusion of labia
NORMAL internal female organs, salt losing crisis
96
congenital adrenal hyperplasia: 21-hydroxylase deficiency: boy presentation
salt losing crisis as infant
or toddler with signs of puberty (non-salt losing)
newborns may not show signs of CAH: sometimes scrotal hyper pigmentation, phallic enlargement
97
salt losing crisis
hyponatremia
hyperkalemia
failure to thrive
98
Dx of 21-hydroxylase deficiency
elevated 17-hydrocyprogesterone
| greater than 3500 ng/dL
99
nonclassical congenital adrenal hyperplasia
reduced 21-hydroxylase function
normal glucocorticoid and mineralocorticoid production
EXCESSIVE androgen production
NO salt wasting
Female does NOT have ambiguous genitalia
Sx in late childhood: premature puberty, acne, accelerated bone age
girls: hirsutism, irregular menstruation
boys: normal testicle function, some have infertility
100
Dx of non classic congenital adrenal hyperplasia
suggested by: 17-hydroxyprogesterone greater than 200 ng/dl
| confirmed with ACTH stimulation test: gold standard: 17-hydroxyprogesterone exceeding 1500 ng/dl
101
primary hyperaldosteronism Sx
```
HTN, hypokalemia, alkalosis, mild/NO hypernatremia (Na regulated by ADH), hypomagnesemia, muscle weakness, CV risks
NO edema (ANP limits Na retention)
```
102
Dx of primary hyperaldosteronism
screen: plasma K
SIMULTANEOUSLY aldosterone: renin ratio greater than 30: specific and sensitive
aldosterone suppression: 2 L normal saline over 4 hrs with pt supine: normal aldosterone: less than 5 ng/dl
103
Tx of primary aldosteronism
1. solitary adrenal adenoma
2. bilateral hyperplasia
1. Sx to remove adrenal gland
| 2. spironolactone, eplerenone
104
endocrine conditions associated with HTN
pheochromocytoma, mineralocorticoid excess, glucocorticoid excess
also: acromegaly, DM, obesity, CAH, estrogen induced, pregnancy induced, renin secreting tumors, hypo/hyperthyroid, liddle syndrome
105
metabolic and vascular manifestations of pheochromocytomas
weight loss, hyperglycemia
| plasma volume contraction: orthostatic hypotension, elevated hematocrit
106
Dx of pheochromocytoma
urine: metanephrines, catecholamines
NE: 280 (normal 15-80)
Epi: can be normal
107
pheochromocytoma Tx
pre-op: alpha and beta blockade, fluid
Sx
post-op: fluids, pressors
108
regulation of aldosterone
volume of ECF
109
syndrome of apparent mineralocorticoid excess
defects or drug/LICORICE inhibition of 11-B-hydroxysteroid dehydrogenase
allows normal cortisol levels to activate aldosterone receptors
110
Cause of hypoglycemia
non-diabetic?
diabetic?
non: RARE: insulinoma, post-GI Sx, tumor, adrenal insufficiency, severe illness (hepatic, renal failure, sepsis), drugs
DM: almost always IATROGENIC
111
alert value for diabetic at risk for hypoglycemia
blood glucose 70 mg/dL (3.9 mmol/L) or less
112
severe hypoglycemia in DM
req. assistance of another to take corrective action
| INCREASES MORTALITY
113
documented symptomatic hypoglycemia in DM
symptoms and low BG (less than 70)
114
asymptomatic hypoglycemia
no symptoms
| low BG
115
probable symptomatic hypoglycemia
symptoms
| didn't take a BG, presume low
116
pseudo-hypoglycemia
symptoms
| normal BG
117
Sx of hypoglycemia
sweat, palpitations, hunger, nervous, dizzy, impaired concentration, blurred vision, tingling
severe: coma, death
118
how does hypoglycemia cause death?
PROLONGED QT (K, Herg channels)
proinflammatory: ICAM, VCAM, E-selectin, VEGF, IL-6
increase platelet activation
decrease fibrinolytic balance (increase PAI-1)
119
syndrome of hypoglycemia associated autonomic failure (HAAF)
reccurent hypoglycemia
hypoglycemia unawareness
defective counter regulation
must re-evalute regimen
120
how many episodes of hypoglycemia does it take to blunt epinephrine response to hypoglycemia?
ONE
| other counter regulators: cortisol, glucagon, GH
121
Whipple's triad
1. sx/signs of hypoglycemia
2. low plasma glucose
3. resolution of Sx when glucose concentration is raised
122
BMI
1. underweight
2. normal
3. overweight
4. obese class I
5. class II
6. class III
1.
123
monogenic causes of obesity
RARE
1. leptin def. or receptor def.
2. melanocortin-4 receptor, POMC mutations
3. PPARy2
4. prohormone convertase-1 mutations
5. TH receptor B mutations
124
orexigenic agents
promote weight gain
1. Neuropeptide Y
2. melanin-concentrating hormone
3. agouti-related peptide
4. Ghrelin
5. opioids
6. endocannabinoids
other: galanin, orexin, dynorphin, B-endorphin, NE/Epi, GHRH, Somatostatin, androgen, progesterone
125
anerexogenic agents
promote weight loss
1. leptin
2. peptide YY
3. alpha melanocyte stimulating hormone
4. GLP-1
5. serotonin
6. cocaine, amphetamines
other: insulin, ciliary neurotrophic factor, urocortin, neurotensin, CRH, bombesin, Cholecystokinin, enterostatin, DA
126
opioids
weight gain
127
endocannabinoids
weight gain
activated by: pain, anxiety
actions: induce appetiete, extinguish aversive memories, inhibit motor behavior, modulate temperature, hormone release and sm. muscle tone
receptors: CB1/2
128
serotonin
weight loss
129
ghrelin
weight gain
130
glucagon-like peptide- 1
weight loss
131
alpha melanocyte stimulating hormone (MSH)
weight loss
| binds MC4R and reduces orexigenic effectors
132
melanin concentrating hormone
weight gain
133
agouti related peptide (AgRP)
weight gain
134
neuropeptide Y (NPY)
weight gain
135
peptide YY
weight loss
136
cocaine-amphetamine regulated peptide (CART)
weight loss
137
leptin
weight loss
made by adipose
inhibits: agouti-related peptide, neuropeptide Y
stimulates: POMC to produce MSH
138
POMC
weight loss
139
obesity Tx
1. BMI over 35
2. 30-35
3. 25-30
1. Sx
2. drugs
3. diet/exercise
140
disease associated with obesity
1. HTN: vascular sm. muscle hypertrophy, increase sympathetic tone: vasoconstriction, increase CO
2. CAD: atherosclerosis (increase LDL)
3. gallstones: increase turnover/excretion of cholesterol
4. CA: estrogen, dietary carcinogens, cholesterol turnover increased
5. HF: increase CO
6. DM: insulin resistance
7. sleep apnea
8. decreased fertility
9. psychosocial
141
polyglandular autoimmune syndrome
autoimmune destruction of several endocrine glands
humoral and cell mediated immune mechanisms
ex: adrenal insufficiency and hypothyroidism
