midterm physio deck 3 Flashcards
myxedema
severe hypothyroidism
signs of hypothyroidism
bradycardiacoarse hairdelayed relaxation of DTRsdry cool pale skingoiternon-pitting edema (myxedema)puffy eyes faceslow movement and speechthinning lateral third of eyebrows
endemic iodide goiter
seaweed ingestion “kombu” in japan –> massive iodide ingestion –> hyperplasia/overactive thyroid
graves disease classic triad
goiterthyrotoxicosisophthalmopathy
antithyroid drugs
tapazole, PYU, lithiumreduced t4 synthesisblock of t4 to t3 conversiondepletion of introthyroid iodine – less t4 synthesis
anti TPO antibodies
suggest hashimoto disease
adrenal glands: short term and long term function
in acute stress = catecholamines mobilize glucose and free FA for fight or flight reactionlong term = glucocorticoids stimulate gluconeogenesis to maintain glucose supply and protect against over-reactions of the body to stress
dual embryonic origins of the adrenal glands
cortex from mesenchyme of the urogenital ridge –> forms a thick inner fetal cortex and a thin outer layer which becomes permanentmedulla is from neural crest cells
cortex steroid hormones are not stored but _____ are
their precursors
zona glomerulosa
outermost cortex layer; secretes aldosterone (mineralcorticoid)
aldosterone function
increases renal sodium retention and potassium/H excretioncontrolled by renin-angiotensin system
zona fasciculata
second adrenal cortex layersecretes glucocorticoids (cortisol)controlled by ACTH
CRH and ACTH
CRH from hypothalamus allows pituitary to release ACTH which causes z. fasciculata to release cortisol
zona reticularis
innermost cortex layer; secretes glucocorticoids and DHEAS (weak androgen)regulated by ACTH
fetal cortex
between medulla and permanent cortexsecretes DHEAS - a major source of estrogen during gestationeventually degenerates
adrenal medulla
part of sympathetic nervous systemmade of postganglionic nerveschromaffin cells secrete catecholamines (epi and norepi)
cortisol
a glucocorticoidmobilizes glucose and free FA for use
how specifically does cortisol work on the z fasciculata
accelerates the activity of rate limiting step in cortisol biosynthesis = the 20,22 desmolase enzyme
ACTH mechanism
membrane receptoradenylate cyclasecAMPprotein kinasesenzymes
chronic ACTH stimulation
(cushings disease) cortex mass increases and secretions rise 20x –> hypercortisolemia and skin bronzing
CRH
corticotropin releasing hormonestimulates the corticotrophs in the anterior pituitary to release ACTH, B endorphin, and B lipotrophin
4 secretory control mechanisms for pituitary ACTH and cortisol
1 - negative feedback by cortisol at pituitary and hypothalamus2 - episodic release (7-15x per day) = pulsatile and variable; more responsive to bursts of stimulation—-in pathologic states: constant stimulation causes downregulation and decreased sensitivity to it3 - diurnal/24 hr rhythm w relation to sleep wake cycle for both cortisol and ACTH—levels highest early in morning, lowest at night4 - stress - fever/surgery/emotions, etc - can be independent of negative feedback in severe stress
how does cortisol travel in blood?
CBG (transcortin) - alpha 2 binding globulin = 80%15% bound to albuminonly 5% is free (active fraction)
cortisol functions
-increase blood glucose-maintain metabolism and circulation in stress-anabolic in liver (gluconeogenesis and ketogenesis); catabolic in other tissues (breakdown of protein and fat)-can induce insulin resistance to keep glucose available for the brain
cortisol and fat distribution
leads to thinning of extremities and truncal fatness
effect of cortisol on circulation
maintains integrity and responsivenessin absence of cortisol, vasodilation occurs and blood pressure falls; glomerular filtration falls and water cant be excreted as fast
effect of cortisol on immune system
blocks inflammatory and immune reactions-stabilizes lysosomal membranes, decrease capillary permeability, and depressed WBCs
the distinguishing feature in cushings disease is….
that set point regulation does occur but it is an abnormal higher level
cushings disease
abnormally high set point –> ACTH is hypersecreted and plasma cortisol increases until it reaches that new set pointadrenal glands hypertrophy due to excess ACTH stimulation**still under regulation though
primary hypercortisolism
cushings syndrome due to adrenal tumorunregulated production of cortisol –> hypothalamic CRH and ACTH are maximally suppressed
ectopic ACTH hypercortisolism
ACTH from ectopic site no tunder regulationdrives a large cortisol production that causes CRH and ACTH from pituitary to be suppressedadrenal cortex hypertrophies**not responsive to usual diagnostic tests since ectopic production is not under control
psychiatric hypercortisolism can be due to
excessive CRH secretion from hypothalamus
iatrogenic cushings syndrome
consumption of excess glucocorticoids –> suppresses entire hypothalamic-pituitary adrenal axis
secondary vs tertiary hypocortisolism
2 - due to pituitary failure3- hypothalamic failure
ACTH stimulates what enzyme?
20,22 desmolase (cyp450)this enzyme converts cholesterol to pregnenolone = the rate limiting step in testosterone, cortisol, and aldosterone production
atrial natriuretic peptide
released by muscle cells in the upper chambers (atria) of the heart (atrial myocytes) in response to high blood volume. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressurepeptide hormone
what is secreted in response to 1) ACTH2) FSH3)LH
1) aldosterone in z glomerulosa, cortisol in z. fasciculata, and androgens in z. reticularis2) estradiol in ovary/testes3) testosterone in the ovary (converted to estrogen) and testes
ACTH/LH/FSH work through what mechanism
G-protein coupled receptors and cAMPGPCR –> GTP –> adenylyl cyclase –> cAMP –> protein kinase –> steroid synthesis
angiotensin 2 works through what mechanism
GPCR + phospholipase ckidney secretes reninrenin converts angiotensinogen to angiotensin 1angiotensin 2 stimulates production of aldosterone (vasoconstriction)GPCR –> GTP –> phospholipase c –> PIP2 converted to DAG and IP3DAG stimulates protein kinase c –> aldosterone productionIP3 opens ca channels on ER and ca increases
glomerulosa –>fasciculata –>reticularis –> medulla –>
g - aldosteronef - cortisol r - androgensm - catecholamines
cortisol effects on1 -muscle glucose uptake2 glucose use3 protein synthesis4 glucose output5 ketogenesis6 glycogenolysis
1 - decreased2 - decreased3 - decreased4 - increased5 - increased6 - increased
without cortisol there will be
hypoglycemiaweaknes/fatigueinfections
how does lack of cortisol cause hypoglycemia
cortisol inhibits the release of insulin and stimulates glucagon –> makes glucose availablewithout cortisol, more is stored
aldosterone does what?
increasing Na and water reuptake and excretion of K –> increases Blood volume and cardiac output!
aldosterone is secreted in response to
low Naincreased blood Kangiotensin ACTH
which is less potent? T or DHT
testosterone is less potent
progesterone is stimulated by what? does what?
stimulated by FSHprepares uteral lining during ovulation and maintains pregnancysecreted by the corpus luteum and placenta
estrogensE1E2E3
E1 - estrone - source of estrogen in post-menopausal women; made in adipose and ovaryE2 - estradiol - predominant in ovariesE3 - estriol - made in placentapotency: E2 > E1 >E3
precursor for MC and GC synthesis?
progesterone(cholesterol –> pregnenolone –> progesterone)
precursor for sex hormone synthesis
androstenedione(cholesterol –> pregnenolone –> 17ahydroxypregnenolone –> DHEA –> androstenedione)
MC and GC both have 21 C…how are they structurally different?
aldosterone has an aldehyde at c18cortisol has an ancohol at c17
main type of enzyme used in steroid synthesis? main rxn type?
cytochrome p450smonooxygenase reactions = insert one oxygen while the other oxygen atom is reduced to water
fatty deposts, moon facies, buffalo hump, muscle weakness, infectionswhat condition?
hypercortisolemia
addisons disease
destruction of the adrenal cortexdue to autoimmune or adrenal tumor (less cortisol)hypoglycemia, dehydration, weightloss, bronzingADRENAL INSUFFICIENCY
3 types of congenital adrenal hyperplasia
cyp21 deficiencycyp11b1 deficiencycyp17 deficiency
cyp21 deficiency
conversion of progesterone to aldosterone and cortisol is blocked so precursors are funneled into sex steroid production–increased progesterone, androgens,and ACTH–> hyponatremia, hirsutism, menstual irregularity, enlarged adrenal glands due to excess ACTH; ambiguous genitalia in neonatesvirilization
cyp 11b1 deficiency
increased DOC and 11deoxycortisol = hypertension due to activation of MC receptorupstream intermediates spill into androgensincreased ACTHvirilization
cyp17 deficiency
hydroxylase and lyase activity inhibited –> those are needed for sex steroid productionincreased aldosterone, DOC, and ACTHdecreased cortisol and no sex steroidsNO virilization
which CAH condition does NOT allow virilization
cyp17 deficiency –> no sex steroid production!
how to treat CAH?
administer prednisone (glucocortiocids) to suppress the ACTH overproduction
what steroid controls body fluid volume?
aldosterone - by increasing Na reabsorption and equal water reabsorption and increased K excretion
where does aldosterone exert effects?
nephron distal tubules, as well as sweat glands, intestines, and salivary glands to decrease Na loss
what treats aldosterone excess?
spironolactoneblocks aldosterone receptors
mechanism of aldosterone
steroid hormone so it binds to intracellular receptorstranslocates to the nucleus –> induces formation of mRNA –> protein synthesis forms anzymes and sodium transporters
is the excretion of K by aldosterone a direct Na/ K exchange?
NO
juxtaglomerular apparatus
in the nephron = a chemo and baro receptor, and a neuroendocrine transducerif perfusion pressure or ion concentration is low, JGA secretes renin which cleaves angiotensinogen to angiotensin 1 (inactive) –> converted to angiotensin 2 by ACE –> angiotensin 2 works on the adrenal cortex and causes increased aldosterone
ACE inhibitors
inhibit ACE from activating angiotensin 1 –>2Anti-HTN drugs
potassium (K) ions act directly on the _________ to stimulate _____
z. glomerulosa; aldosterone
aldosterone excess causes
hypokalemia and hypertensonhypokalemia results in polyuria and weakness/paralysis
chronic edema leads to shrunken blood volumepersistent leak of effective blood volume into the abdomen results in…
increased levels of renin-angiotensin and increased aldosterone (excess) –> stimulus for aldosterone secretion never turns offdespite high aldosterone, fluid volume stays low and BP is low/normal due to continuous leak
PNMT
phenyl M methyl transferasemade by chromaffin cells in the adrenal medullaconverts norepi to epinephrine
blood supply of medulla
arterioles carry fresh blood to medulla, bypassing cortexmixes with blood from cortical sinuses
circulating norepi reflects ____?circulating epi reflects ____?
vascular sympathetic toneadrenal meduallary secretion
catecholamines on alpha receptor
norepi >epiincreased gluconeogenesisdecreased insulinincreased artery constriction in renal, genital and splanchnic circulationincreased sweating and pupil dilation
catecholamines on B receptor
epi>norepiincreased glycogenolysis, lipolysis and ketosisincreased insulin and glucagon secretionincreased muscle K uptakearteriolar dilation in muscleincreased heart contractility and heart raterenin secretion Thyroid and parathyroid hormone secretion
catecholamine biosynthesisrate limiting step?last step?
rls = tyrosine hydroxylase (1st step)last = PNMT (induced by cortisol) = why medulla needs to be within the cortex
catecholamine excess
pheochromocytomacatechlamine secreting tumor of the adrenal medullaexcess epi and norepi signs: headache, sweating, forceful heartbeat, anxiety, tremor, fatigue, nausea, chest pain, visual disturbances
