Things I don't know: PathoPhys Flashcards
What should you do before giving TH in SEVERE hypothyroidism?
replace corticosteroids
Sx of thyrotoxic crisis
SOB, tachycardia, afib, vomit, diarrhea, jaundice, lost lots of weight
hyperthyroid that DIDN’T TAKE THYROID MEDS
Tx of thyroid storm
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
Mechanisms of damage in high glucose
- polyol pathway: sorbitol
- AGE formation (advanced glycation end product): ROS production
- PKC activation
- increased hexosamines
- PARP (poly ADP ribose polymerase)
- epigenetic (methylation/demethylation)
Who is at an increased risk of diabetic nephropathy? Most sensitive test?
increased urine albumin excretion
if untreated leads to end stage renal disease
maintain normal UAE: no nephropathy
How does insulin Tx affect someone with increased GFR and UAE?
UAE: returns to normal in T1DM, and many in T2DM return to normal
GFR: may remain elevated in both
What almost always accompanies proteinuria?
increase in BP
How long does it take micro-albuminuria to develop in T1DM?
5-15 yrs
What increases likelihood of lower limb amputation in diabetic?
symptoms of peripheral neuropathy
positive symptoms of diabetic peripheral neuropathy
pain, paresthesia, dysesthesia, allodynia
negative symptoms of diabetic peripheral neuropathy
decrease sensation to temp., pain, touch, motor movement
clinical staging of diabetic nephropathy
- nonproliferative diabetic retinopathy (NPDR): asymptomatic
- preproliferative diabetic retinopathy: laser therapy can prevent vision loss
- proliferative diabetic retinopathy (PDR): major cause of vision loss
epsilon cell of pancreas
secrete ghrelin
gamma cell
PP cell
secretes pancreatic peptide
Fn3K
deglycation of RBC
What causes the islet damage in DM?
islet specific T cells
Ab: GAD, ICA, IAA, ZnT8
HLA DR2/DR2
protective against T1DM
DQ beta chain
neg: susceptible to T1DM
pos: protection from T1DM
can be in middle
DR4/DR4 overrides protection
DQ7
primary protection against T1DM
DQ8
primary susceptibility to T1DM
amylin
B cells of pancreas
decrease gastric emptying
decrease glucagon secretion
promotes satiety
GLP-1
increase insulin secretion
decrease glucagon and gastric emptying
What can cause mental status change in SIADH?
brain swells
can also cause seizures
What osmotic factors can stimulate ADH?
Na, mannitol, urea
NOT: glucose
What are the non-osmotic factors than stimulate ADH?
hypotension, hypovolemia N/V hypoglycemia renin-angiotensin Pain, stress, emotion?
Factors that alter AQP2 levels
- increase
- decrease
- CHF, pregnancy, SIADH
2. DI, postobstructive polyuria, chronic renal failure
Normal serum Na
136-145 mEq/L
What is renal tubular Na reabsorption regulated by?
- SGLT
- ANP
- Renin-angiotensin-aldosterone
causes of hyponatremia
- hypovolemic
- hypervolemic
- euvolemic
- high urine output and Na excretion, increase ANP
- edema (nephrotic syndrome, CHF, cirrhosis), water intoxication
- ADH mediated water retention
clinical presentation of hyponatremia
- early
- later
- chronic
- N/V, headache
- seizure, coma, resp. arrest
- lethargy, confusion, muscle cramps, neuro impairment
causes of SIADH
paraneoplastic trauma CVA infection: pulmonary, brain, near drugs: cancer, psych
Tx SIADH
FLUID RESTRICTION
demeclocycline, lithium, vaptans
hypernatremia Sx
thirst, lethargy, irritable, seizure, fever, oliguria
Causes of hypernatremia
- DI
- Na excess
- water depletion exceeding Na depletion: diarrhea, vomit, dehydration
- drugs: lithium, cyclophosphamide, cisplatin
DIDMOAD syndrome
familial
central DI
DM, nerve deafness, optic atrophy, bladder and ureter atonia
water deprivation test
- Uosm after vasopressin increases 50%
- less than 50%
- central DI
2. nephrogenic DI or psychogenic
familial hypocalciuric hypercalcemia
AD inactivating mutation in CaSR mildly increased serum Ca and PTH asymptomatic low urine Ca (unlike primary hyperparathyroidism) Tx: no intervention
drugs that induce hypercalcemia
lithium
HCTZ
PTH independent hypercalcemia
- tumor: PTHrP or bone metastases
- granulomatous disease (TB, sarcoidosis, lymphoma): increase vit. D
- multiple myeloma
- hyperthyroidism, adrenal failure
- immobilization
- medications: Vit. D, Vit. A, milk-alkali syndrome
primary hyperparathyroidism work up
- Ca, albumin
- PTH
- 25-OH vit. D
- 24 hour urine Ca (to differentiate from FHH)
- imaging: thyroid US (localize), 99Tc-sestamibi scan (localize), DXA
criteria that indicates parathyroidectomy
- Ca above 1 mg/dL above UNL
- less than 50 yrs old
- osteoporosis
- renal insufficiency
nonsurgical Tx for hyperparathyroidism
hydrate
bisphosphonates
Vit. D maintenance
cinacalcet
if hypercalcemia is due to malignancy, what will PTH be
suppressed
breast and squamous cell CA most common
What causes hypercalcemia in malignancy?
PTHrP
bony metastasis
cytokines activating osteoclasts
multiple myeloma: destroys bone
how do granulomatous disease cause hypercalcemia
increase 1 alpha hydroxylase which increases Vit. D
increase Ca, PO4
decrease PTH
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
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
weird causes of hypocalcemia
- acute pancreatitis: free FA chelate Ca
- massive transfusion: citrate binds Ca
- tumor lysis syndrome or rhabdomyolysis: Pi released binds Ca
- meds: Pi, bisphosphonates
- hungry bone syndrome
Sx of hypocalcemia
agitation HYPERREFLEXIA convulsions HTN long QT
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
pseudohypoparathyroidism
mutation in Gs alpha subunit
PTH resistance
hypocalcemia, hyperphosphatemia, high PTH
short stature, round face, short 4th metacarpal, obesity, Albright’s hereditary osteodystrophy
acute hypocalcemia crisis Tx
ALWAYS correct MAGNESIUM if low
Ca gluconate
long term hypocalcemia Tx
- Ca
- Vit. D (need active form unless PTH is present)
- Hydrochlorothiazide: increase renal reabsorption of Ca in distal tubule
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
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
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
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
Causes of DKA and HHS
new DM
failure to take insulin
infection or medical illness
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
presentation of HHS
polydipsia, polyuria, weak, hypothermia, tachycardia, altered sensorium
unique: Sx of accompanying illness, poor appetite, MENTAL STATUS CHANGE, HYPOTENSION
LONG ONSET
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
anion gap
AG = Na - (Cl + HCO3)
serum osmolarity
2Na + glucose/18 + BUN/2.8
Tx in
- DKA
- 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
corrected Na
(1.6 x glucose -100)/ 100
DKA serum
- Na
- K
- hyponatremia
2. hyperkalemia
markers for bone formation
ALP
osteocalcin
carboxyterminal propeptide of type 1 collagen (P1NP)
markers for bone resorption
N-telopeptide
carboxyterminal of type 1 collagen (CTX-1)
DXA
gold standard to measure bone mineral density (important predictor of fractures)
clinical evaluation of osteoporosis
Ca, PO4, inactive (25) Vit. D, DXA
T score of osteoporosis Dx
less than -2.5
or LOW TRAUMA fracture and greater than -2.5
meds that increase fracture risk
glucocorticoids, TCA, benzodiazepines, antipsychotics, PPIs, SSRIs, anticonvulsants, aromatase inhibitors, androgen deprivation therapy
fracture risks
femoral neck T score age previous low trauma fracture low BMI smoking steroids RA High alcohol use family Hx
endocrine mediated causes of low bone mass density
cushing's hypercalcemia, kidney stones acromegaly hypogonadism hyperthyroidism
Tx of osteoprosis
stop smoking/drinking
increase exercise
Ca, Vit. D
fall prevention
Osteoporosis: who do you give meds
- T score less than -2.5 after age 50
- osteopenia with Hx of fragility fracture
- use FRAX score for under 50 and T score less than -2.5 or older than 50 with greater than -2.5
inherited Ricket’s
AR
low Vit. D: 1 alpha hydroxyls deficiency
high Vit. D: receptor defect
Bone pain
fibrous dysplasia
osteitis fibrosa cystica
osteogenesis imperfecta
Paget’s
McCune-Albright
GNAS1 gene mutation precocious puberty fibrous dysplasia cafe au lait hypophosphatemia due to FGF-23
corrected Ca (when albumin is low)
(0.8 x (4 - patient’s albumin) + serum Ca
most common cause of acromegaly
pituitary MACROadenoma
What are GH levels after oGTT?
normal
acromegaly
normal: less than 1 ng/ml
acro: greater than 2 ng/ml
acromegaly Sx
large hands, feet maxillofacial change arthralgia excess sweating headache hypogonadal sleep apnea HTN DM
Prolactin levels
- normal
- prolactinoma
- macroprolactinoma
- lower than 25 ug/l
- greater than 250
- greater than 500
drugs that cause high prolactin
antipsychotics: DA antagonist
reserpine, haloperidol
labs for TSH secreting pituitary adenoma
RARE
high T4 and TSH
confirm with MRI
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
commonly one of the first derangements of cushings
failure to achieve normal late night (11pm to 1am low cortisol) circadian nadir
Dx of cushing
- 24 hour urine free cortisol
- late night salivary cortisol
- 1 mg overnight dexamethaonse suppression test (give 1 mg at 11pm-12am and measure at 8am)
- longer low dose DST (2 day, 2 mg dose every 6 hours for 8 doses; check 2 or 6 hours after last dose)
Who gets false positives for overnight dexamethasone suppression test?
why?
women on oral contraceptives
increase CBG, but measure total cortisol rather than free
what should cortisol be in dexamethasone suppression test
normal: less than 1.8 mug/dl
what should you suspect in a patient with acute unexplained volume depletion and shock
acute adrenal insufficiency
hyperkalemia, acidosis, hypoglycemia
Dx of adrenal insufficiency
ACTH stimulation test
mutation in CYP21A2 gene
21-hydroxylase deficiency
can’t convert 17-hydroxyprogesterone to 11-deoxycortisol
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
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
salt losing crisis
hyponatremia
hyperkalemia
failure to thrive
Dx of 21-hydroxylase deficiency
elevated 17-hydrocyprogesterone
greater than 3500 ng/dL
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
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
primary hyperaldosteronism Sx
HTN, hypokalemia, alkalosis, mild/NO hypernatremia (Na regulated by ADH), hypomagnesemia, muscle weakness, CV risks NO edema (ANP limits Na retention)
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
Tx of primary aldosteronism
- solitary adrenal adenoma
- bilateral hyperplasia
- Sx to remove adrenal gland
2. spironolactone, eplerenone
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
metabolic and vascular manifestations of pheochromocytomas
weight loss, hyperglycemia
plasma volume contraction: orthostatic hypotension, elevated hematocrit
Dx of pheochromocytoma
urine: metanephrines, catecholamines
NE: 280 (normal 15-80)
Epi: can be normal
pheochromocytoma Tx
pre-op: alpha and beta blockade, fluid
Sx
post-op: fluids, pressors
regulation of aldosterone
volume of ECF
syndrome of apparent mineralocorticoid excess
defects or drug/LICORICE inhibition of 11-B-hydroxysteroid dehydrogenase
allows normal cortisol levels to activate aldosterone receptors
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
alert value for diabetic at risk for hypoglycemia
blood glucose 70 mg/dL (3.9 mmol/L) or less
severe hypoglycemia in DM
req. assistance of another to take corrective action
INCREASES MORTALITY
documented symptomatic hypoglycemia in DM
symptoms and low BG (less than 70)
asymptomatic hypoglycemia
no symptoms
low BG
probable symptomatic hypoglycemia
symptoms
didn’t take a BG, presume low
pseudo-hypoglycemia
symptoms
normal BG
Sx of hypoglycemia
sweat, palpitations, hunger, nervous, dizzy, impaired concentration, blurred vision, tingling
severe: coma, death
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)
syndrome of hypoglycemia associated autonomic failure (HAAF)
reccurent hypoglycemia
hypoglycemia unawareness
defective counter regulation
must re-evalute regimen
how many episodes of hypoglycemia does it take to blunt epinephrine response to hypoglycemia?
ONE
other counter regulators: cortisol, glucagon, GH
Whipple’s triad
- sx/signs of hypoglycemia
- low plasma glucose
- resolution of Sx when glucose concentration is raised
BMI
- underweight
- normal
- overweight
- obese class I
- class II
- class III
1.
monogenic causes of obesity
RARE
- leptin def. or receptor def.
- melanocortin-4 receptor, POMC mutations
- PPARy2
- prohormone convertase-1 mutations
- TH receptor B mutations
orexigenic agents
promote weight gain
- Neuropeptide Y
- melanin-concentrating hormone
- agouti-related peptide
- Ghrelin
- opioids
- endocannabinoids
other: galanin, orexin, dynorphin, B-endorphin, NE/Epi, GHRH, Somatostatin, androgen, progesterone
anerexogenic agents
promote weight loss
- leptin
- peptide YY
- alpha melanocyte stimulating hormone
- GLP-1
- serotonin
- cocaine, amphetamines
other: insulin, ciliary neurotrophic factor, urocortin, neurotensin, CRH, bombesin, Cholecystokinin, enterostatin, DA
opioids
weight gain
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
serotonin
weight loss
ghrelin
weight gain
glucagon-like peptide- 1
weight loss
alpha melanocyte stimulating hormone (MSH)
weight loss
binds MC4R and reduces orexigenic effectors
melanin concentrating hormone
weight gain
agouti related peptide (AgRP)
weight gain
neuropeptide Y (NPY)
weight gain
peptide YY
weight loss
cocaine-amphetamine regulated peptide (CART)
weight loss
leptin
weight loss
made by adipose
inhibits: agouti-related peptide, neuropeptide Y
stimulates: POMC to produce MSH
POMC
weight loss
obesity Tx
- BMI over 35
- 30-35
- 25-30
- Sx
- drugs
- diet/exercise
disease associated with obesity
- HTN: vascular sm. muscle hypertrophy, increase sympathetic tone: vasoconstriction, increase CO
- CAD: atherosclerosis (increase LDL)
- gallstones: increase turnover/excretion of cholesterol
- CA: estrogen, dietary carcinogens, cholesterol turnover increased
- HF: increase CO
- DM: insulin resistance
- sleep apnea
- decreased fertility
- psychosocial
polyglandular autoimmune syndrome
autoimmune destruction of several endocrine glands
humoral and cell mediated immune mechanisms
ex: adrenal insufficiency and hypothyroidism
