3/7 endo Flashcards
A drug is virtually eliminated after how many half lives?
-5
t1/2 = Vd (.7)/Cl
Acute viral hepatitis
-do you see necrosis or apoptosis?
-both
Councilman body
- apoptotic hepatocytes
- acidophillic
IV drug user w/hepatitis
-which hepatitis most likely?
-Hep C
beta-glucoronidase
- who releases it?
- what does it lead to?
- following infection of biliary tree, injured hepatocytes and bacteria release this enzyme.
- unconjugates bili = more unconjugated bili in bile = brown pigment stone.
Progesterone & gallstones
- slows gallbladder emptying
- reduces bile acid secretion
- gallbladder hypomotility => stones
Why are pregnant or OCP using women more at risk for gallstones?
- inc cholesterol synth via estrogen.
- gallbladder hypomotility via progesterone.
Bimodal distribution of plasma drug levels
- think of what?
- most drugs = unimodal
-fast v slow acetylators.
What is the most common benign liver tumor?
- cavernous hemangioma.
* do NOT biopsy these! risk of hemorrhage!
Thyroid diverticulum
- arises from where? descends to where?
- connected to tongue via?
- arises from floor of primitive pharynx, and descends into neck.
- Connected to tongue by thyroglossal duct, which normally disappears but may persist as pyramidal lobe of thyroid.
pyramidal lobe of thyroid
-persistence of what?
thyroglossal duct
Normal remnant of thyroglossal duct
Foramen cecum
Foramen cecum
Normal remnant of thyroglossal duct
Most common ectopic thyroid tissue site?
Tongue
-presents as mass at base of the tongue.
Presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue
Thyroglossal duct cyst
Adrenal cortex derived from…
mesoderm
Adrenal medulla derived from..
neural crest
Is aldo secretion controlled by ACTH?
NO
-AT2 and hyperkalemia.
adrenal medulla
-under control of what?
Blood pressure
-sympathetic response
Does LH affect steroid hormone synthesis in adrenals?
No
-only affects gonadal cells.
Neuroblastoma vs pheochromocytoma
-which one causes HTN?
- pheo causes episodic HTN.
- neuroblastoma rarely causes HTN.
Neuroblastoma
-presentation
- often presents w/abdominal distention.
- it typically crosses the midline (unlike Wilm’s tumor).
Hypophysis
-what is it?
Entire pituitary
What protein transfers ADH & oxytocin from hypothalamus down to post. pit?
-mutations in this protein can lead to what?
- neurophysins
- point mutations to neurophysin 2 underlie most cases of hereditary hypothalamic diabetes insipidus.
Post pit. derived from what?
Neuroectoderm
Ant pit. derived from what?
Oral ectoderm (Rathke pouch).
Ant. pit hormones
-alpha or beta subunit: which determines hormone’s specificity?
β subunit—determines hormone specificity.
Ant. pit hormones:
-Same α subunit shared by which hormones?
TSH, LH, FSH, and hCG.
Ant. pit hormones:
- which hormones = acidophils?
- mnemonic?
- GH, prolactin.
- GPA: GH, Prolactin = Acidophils.
Ant. pit hormones:
- which hormones = basophils?
- mnemonic?
- B-FLAT
- basophils - FSH, LH, ACTH, TSH
Why is C-peptide a good marker for insulin secretion?
- 1:1 secretion w/insulin
- does not undergo significant first pass metabolism
- not included in exogenous insulin
Which GLUT transporter is the glucose sensor for liver/pancreatic beta cells?
GLUT2
glucose vs insulin
-which can cross the placenta? can both?
- glucose can cross.
- insulin can not cross.
Insulin-independent glucose uptake:
-mnemonic:
BRICK-L
-Brain, RBCs, Intestine, Cornea, Kidney, Liver.
GH influence on insulin levels
- causes insulin resistance.
- this increases insulin release.
beta-2 agonists
-effect on insulin release
-inc. insulin release
but inc. glucagon release more i believe
Glucose influence on GH
-glucose should inhibit GH release
Insulin
- pathway for insulin release & protein/fat/glycogen synth:
- pathway for txn alteration:
- insulin release + synthesis: IP3/PKC
- txn alteration: RAS/MAP kinase
CRH from hypoT stimulates release of what?
ACTH, MSH, β-endorphin
*POMC = precursor to these 3
Dopamine
-effect on PRL?
inhibits prolactin secretion
What prevents lactogenesis during pregnancy?
-during pregnancy, the high amount of E & P made by
placenta will prevent prolactin from causing lactogenesis.
Somatostatin inhibits release of which pituitary hormones?
- GH, TSH
* octreotide used to treat acromegaly.
TRH
-causes inc in which hormone?
- TSH, prolactin
- All hormones are super exclusive, only act on their specific receptor, except TRH. TRH can make prolactin go up.
If you cut pituitary stalk, which is the only hormone that will increase?
Prolactin
- its under tonic inhibitory control by dopamine.
- dopamine being made by hypothalamus.
Link btwn primary hypothyroidism (ie. hashimotos) and galactorrhea.
- In primary hypothyroidism (ie. hashimotos) you have inc. TRH & inc. TSH.
- this can lead to inc. PRL and galactorrhea in women.
Somatotropes =
cells in ant. pit. that produce GH
Which AAs stimulate GH secretion?
arginine & histidine
Somatomedin effect on GH.
-Somatomedin also has INDIRECT neg. feedback on GH by stimulating stomatostatin production.
What inhibits GH secretion?
Somatostatin & glucose
Glucose tolerance test
If GH isn’t down-regulated w/glucose infusion then you could have pituitary adenoma secreting GH = acromegaly/gigantism.
ADH
-made in which hypoT nuclei?
supraoptic nuclei
Tx for central DI?
Desmopressin (ADH analog)
-does NOT have V1 vasoconstrictive properties of ADH.
Where are osmoreceptors?
hypothalamus
*threshold to signal thirst = lower in pregnant women. One way pregnant women inc. their plasma level.
Cholesterol => pregnenolone
- whats the enzyme?
- whats enzyme controlled by?
Cholesterol desmolase
- ACTH stimulates it (reticulara & fasciculata)
- AT2/potassium stimulates it (glomerulosa)
-Ketoconazole inhibits it.
Triple test
-fetal
Checks for b-HCG, AFP, estriol
-btwn weeks 16 & 18.
AFP
-what makes it?
- fetal liver
- fetal GI tract
- early gestational yolk sac
Most common cause of elevated AFP levels?
Dating error.
- under-estimation of gestational age.
- other causes: neural tube defects, ant abdominal wall defects (omphalocele, gastroschisis), multiple gestation.
Down’s syndrome
-inc. or dec. AFP?
-dec. AFP.
Dec. fetal estriol levels suggest what?
- placental insufficiency.
- intrauterine growth retardation.
Inc. HCG
-associated w/what?
- hydatidiform mole
- multiple gestation
- choriocarcinoma
Is Afib specific for graves?
-or can it happen in any hyperthyroid condition?
- not specific for graves.
- can happen in any hyperthyroid condition.
Heat intolerance
-found in hypo or hyperthyroidism?
- hyperthyroidism
- you can’t tolerate heat b/c you’re already making so much heat in your body.
Why would ALP be increased in hyperthyroidism?
-due to the increased bone resorption.
Glitazones
-mechanism?
- inc. tissue sensitivity to insulin.
- binds PPAR-gamma nuclear txn regulator.
Which DM drugs alone can cause hypoglycemia?
-sulfonylureas & insulin.
Sex steroid effect on growth plate.
-how does this differ from IGF-1 affect?
- Initially inc. linear growth then encourage closure of epiphyseal plate (aka, fuse w/metaphysis).
- IGF-1 never encourages closure. Just growth.
*estrogen responsible for closing the epiphyseal plate.
- Are adiponectin levels high or low in DM2?
- Which drug inc. their levels and how?
- adiponectin is LOW in DM2.
- secreted by adipocytes.
- glitazones inc adiponectin levels by activating their txn factor, PPAR-gamma. Inc. levels will dec. insulin resistance.
MEN 1
-mnemonic
PPP
- parathyroid tumor (hypercalcemia)
- pancreatic tumor (gastrin)
- pituitary adenoma (PRL, ACTH)
MEN 2A
MPP
- medullary carcinoma of thyroid (calcitonin)
- pheochromocytoma
- parathyroid tumor (
MEN 2B
MPM
- medullary carcinoma of thyroid (calcitonin)
- pheochromocytoma
- marfanoid habitus/mucosal neuromas
Where can you find 5-alpha-reductase?
-prostate, testes, hair follicles, adrenals
What is lipotoxicity?
-too much FFAs inc. insulin resistance & reduces the amount of insulin that is released.
Glucose => sorbitol
-but what is sorbitol converted to?
- fructose via sorbitol DH
* both sorbitol & fructose are osmotically active.
Chlorthalidone
-what is it?
thiazide diuretic
Long term exogenous glucocorticoid use
-effect on HPA axis?
- suppresses HPA axis
- reduced CRH, ACTH, cortisol.
- all 3 are decreased!
Adrenal insufficiency
-whats the most common cause?
-HPA axis suppression due to exogenous glucocorticoid use.
What type of necrosis is seen in sheehan syndrome
- coagulation necrosis
- not liquefactive b/c pituitary is not part of the brain.
Atheletes/anorexic women who dont menstruate, whats the cause?
-hypogonadotropic amenorrhea.
Link btwn prolactin and femoral fracture
- PRL inhibits GnRH = less FSH & LH = less estrogen.
- Estrogen = protective of bone.
- Reduced estrogen can lead to osteoporosis.
17α-hydroxylase
-inc or dec aldo?
- dec aldo
- may seem counter-intuitive
- make so much 11-doc before getting to aldo that you get HTN and dec. renin/AT2.
Cortisol effect on alpha-1 receptors
up-regulates them
-remember, cortisol is permissive on catecholamines and glucagon.
Cortisol effect on:
- mast cells
- eosinophils
- IL-2
- blocks histamine release from mast cells.
- reduces eosinophils.
- blocks IL-2 production
Exogenous corticosteroids can cause reactivation of:
-TB and candidiasis (blocked IL-2 production).
Which cells make PTH?
Chief cells of parathyroid.
Regulation of PTH by Mg
-inc or dec?
- dec. Mg => inc. PTH
- severely dec. Mg => dec. PTH
*Common causes of dec. Mg2+ include diarrhea, aminoglycosides, diuretics, and alcohol abuse.
*Common causes of dec. Mg2+:
-diarrhea, aminoglycosides, diuretics, and alcohol abuse.
Alkalosis
-effect on Ca level?
- Albumin deprotonated, now has even more (-) charge, binds Ca.
- free calcium decreased.
- alkalosis can lead to Sxs of hypocalcemia.
Which cells make calcitonin?
-Parafollicular cells (C cells) of thyroid.
HPA hormones that use cAMP pathway
-mnemonic?
FLAT ChAMP
-FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2-receptor), MSH, PTH, calcitonin, GHRH, glucagon.
HPA hormones that use IP3 pathawy
-mnemonic?
GOAT HAG
- GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1
- receptor), Angiotensin II, Gastrin.
Thyroid hormones
-which signaling pathway do these use?
-steroid receptor.
OCPs, pregnancy effect on sex hormone binding globulins.
inc. SHBG (free estrogen levels remain unchanged).
- sex hormone binding globulin.
Thyroxine relationship w/GH
thyroxine is permissive on GH.
Thyroxine sets metabolic rate for all tissues except:
- all tissues in the body except the brain, gonads & uterus.
- although dont forget, you need thyroxine for CNS formation in utero.
Thyroxine effect on heart
-up-reg beta-1 receptors on heart.
How does thyroxine inc. basal metabolic rate?
inc. Na/K ATPase activity
Thyroxine 4 functions
- Brain maturation
- Bone growth
- β-adrenergic effects
- Basal metabolic rate inc.
Wolff-Chaikoff effect:
excess iodine temporarily inhibits thyroid peroxidase => dec. iodine organification => dec. T3/T4 production.
What are the only cells in the body that can absorb iodine?
Thyroid follicular cells
TBG inc or dec in…
- hepatic failure
- pregnancy
- OCP use
- hepatic failure: dec.
- pregnancy: inc.
- OCP use: inc.
*estrogen inc. TBG production.
-inc total T4 w/normal TSH levels =
- you’re on estrogen.
- inc. in thyroid binding globulin.
Waist to hip ratio
waist = visceral fat
hip = subQ fat
-high visceral fat = high correlation w/insulin resistance.
LDL receptor
-mechanism of getting it into the cell?
Endocytosis w/clathrin coated vesicles.
Primary hyperaldosteronism
-whats the serum sodium?
NORMAL serum sodium due to aldosterone escape!
Diarrhea
-what do you lose?
Water, potassium, bicarb
- Get hypernatremia (cuz u lose water).
- hypokalemic
- metabolic acidosis.
