Cholesterol & Steroid Metabolism Flashcards
SLOS:
Smith‐Lemli‐Opitz
Syndrome
Autosomal Recessive
microencephaly
embryonic malformations
surviving children have an IQ of
20‐40
partial deficiency of 7‐ dehydrocholesterol reductase: needed for the correct double‐ bond formation in ring B to make a complete cholesterol structure
Cholelithiasis
Bile Salt Deficiency
Lecithin Deficiency
cholesterol precipitates in the
gall bladder
possible causes: -malabsorption of bile acids from the intestine -obstruction of biliary tract interruption of enterohepatic circulation -decreased bile production (hepatic dysfunction) -accelerated rate of bile recycling (excessive suppression of bile synthesis)
Treatment -surgical removal of gall bladder -chenodeoxycholic acid (chenodiol) -disintegration of bile stones by shock waves -dissolution w/ methyl‐tert‐ butyl ether
Acute Pancreatitis
pancreatic amylase and lipase in
the serum
caused by migrating gallstones
that obstruct the ampulla of Vater
Adreno‐Cortico‐Tropic
Hormone (ACTH)
aka: corticotropin
release is stimulated by
corticotropin releasing hormone
(CRH) from the hypothalamus
pituitary gland
stress hormone that stimulates hormone synthesis (glucocorticoids) in the adrenal cortex: stimulates synthesis and release of cortisol
cortisol is the feedback inhibitor for
ACTH release
Cortisol
Hormone: Dominant
Glucocorticoid
- synthesized from progesterone in the zona fasciculata of the adrenal cortex
- stress adaptation
- elevates blood pressure
- elevates Na+ uptake
- immune system effects
- anti‐inflammatory
-needed in the liver for gluconeogenesis (especially during prolonged starvation)
-degradation of muscle protein
(counteracts insulin, which leads to muscle protein synthesis)
-inhibition of stimulated phospholipase A2
-inhibits induction of COX‐2
Aldosterone
Hormone: Dominant Mineralcorticoid
- produced from progesterone in the zona glomerulosa of the adrenal cortex stimulates renal reabsorption of Na+ and excretion of K+
- elevates blood pressure
-stimulated by angiotensin II/III
ACTH stimulates aldosterone
synthesis
Estrogen
-control menstrual cycle
-promote development of female
secondary sex characteristics
stimulated by FSH
Progesterone
-secretory phase of uterus and
mammary glands
-implantation and maturation of
fertilized ovum
-stimulated by LH
-produced directly from
pregnenolone and secreted from
the corpus luteum
Estradiol
produced in the ovary
secondary female sex
characteristics
stimulated by FSH
Androgens:
Dehydroepiandrosterone
Androstenedione
Testosterone
- stimulates spermatogenesis
- promotes development of male
- secondary sex characteristics
- promotes anabolism
- masculinization of the fetus
-produced by the adrenal z. reticularis and z. fasciculata -testosterone is synthesized in the testes, produced from progesterone -stimulated by LH
17‐a‐hydroxylase/ CYP 17A1/ P450c17 deficiency
- female‐like genitalia
- Na+ and fluid retention
- hypertension
build up of progesterone
- virtually no sex hormones or cortisol
- increased production of mineralcorticoids
21‐a‐hydroxylase/ CYP 21A2/ P450c21 deficiency
- most common form
- masculinization of external genitalia in females and early virilization in males
build up of 17‐a‐
hydroxyprogesterone
-partially and virtually complete deficiencies are known
-mineralcorticoids and
glucocorticoids are virtually
absent (classic form) or deficient
(non‐classic form)
11‐B‐hydroxylase/ CYP11B/ P450c11 deficiency
- fluid retention
- low‐renin hypertension
- masculinization
- virilization
build up of 11‐deoxycorticosterone
- decrease in serum cortisol, aldosterone, corticosterone
- increased production of deoxycorticosterone causes fluid retention
- hormone supresses renin/angiotensin system
3-B-hydroxysteroid dehydrogenase deficiency
- no glucocorticoids, mineralcorticoids, active androgens, estrogens
- salt excretion in urine
- female like genitilia
Cushing’s Syndrome:
Hypercortisolism
Adrenocortical Tumor: Hyperfunction of AdrenalCortex
glucocorticoid excess leads to
- protein loss
- characteristic fat distribution‐‐face, neck, truncus
- hirsutism (abnormal hair growth)
- early pubic hair
Addison’s Disease
Primary Adrenal Cortical
Insufficiency
-adrenal cortex atrophy due to disease
-autoimmune destruction
-aldosterone and cortisol levels are low
- ACTH is high, which does not lead
to hyperplasia due to cortex atrophy
failure to thrive muscle weakness fatigue weight loss hyperpigmentation salt craving hyponatremia hypokalemia hypovolemia hypotension abdominal pain vomiting constipation
Glucocorticoid Therapy
Drug: Inflammation
-asthma treatment
-anti‐inflammatory
-extended corticosteroid therapy
can lead to cushingoid features‐‐
low ACTH, high cortisol
synthetic glucocorticoid analogues
bind less to transcortin and enter
in large amount in the cells
