Physiology Flashcards
What is the thyroid derived from?
floor of primitive pharynx, descends into neck
what are the remnants of the thyroglossal duct
pyramidal lobe of thyroid and foramen cecum
What is the most common site of ectopic thyroid tissue?
base of the tongue-> lingual thyroid
What are the symptoms of a thyroglossal duct cyst?
cystic dilation of thyroglossal duct remnant; presents as anterior midline neck mass that moves with swallowing
What are the thyroid follicular cells derived from?
outpouched pharyngeal epithelium
What are the thyroid parafollicular cells (C-cells) derived from?
4th pharyngeal pouch
What do the thyroid follicular cells produce? What do the thyroid parafollicular cells (C cells) produce?
follicular cells - T3 and T4
parafollicular cells - calcitonin
What are the adrenal cortex and medulla derived from?
adrenal cortex- mesoderm
medulla - neural crest
What are the layers of the adrenal cortex?
Zona glomerulosa (most peripheral) Zona fasciculata Zona reticularis (most internal)
What are the secretory products from the zona glomerulosa and what is the primary regulatory control?
produces Aldosterone in response to increased Renin-angiotensin (low BP/low osmolarity)
What are the secretory products from the zona fasciulata and what is the primary regulatory control?
Produces cortisol and sex hormones in response to increased ACTH, CRH
What are the secretory products from the zona reticularis and what is the primary regulatory control?
Produces sex hormones in response to increased ACTH, CRH
What are the cells of the adrenal medulla and what are their secretory products and primary regulatory control?
Chromaffin cells
Secretory product: catecholamines (E 80%, NE 20%)
Primary regulatory control: Preganglionic sympathetic fibers releasing ACh
What is the most common tumor of the adrenal medulla in adults? in children?
Adults - pheochromocytoma (episodic HTN)
Children - neuroblastoma (rarely causes HTN)
What is the anterior pituitary (adenohypophysis) derived from?
Derived from oral ectoderm; out-pouching of pharyngeal roof: Rathke’s pouch
What are the hormones secreted by the anterior pituitary and which are acidophils and which are basophils?
Acidophils - GH, prolactin
Basophils - FSH, LH, ACTH, TSH
Which hormones have a common alpha subunit? How are they differentiated?
TSH, LH, FSH and hCG have common alpha subunit
Beta subunit determines specificity
What is the posterior pituitary (neurohypophysis) derived from?
derived from neuroectoderm; extension of hypothalamic neurons
Where are ADH and oxytocin made?
Both made in the hypothalamus: ADH - supraoptic nuclei, oxytocin - paraventricular nuclei
How are ADH and oxytocin transported to the posterior pituitary?
From the hypothalamus via neurophysins (carrier protiens)
What are the endocrine pancreas cell types and what do they produce?
alpha cells: glucagon (peripheral) ~30%
beta cells: insulin (central) ~70%
delta cells: somatostatin (interspersed)
How is insulin synthesized?
preproinsulin (synth in RER) cleaved into “presignal” and proinsulin (stored in secretory granules) -> cleavage of proinsulin into insulin and C-peptide (exocytosis)
What type of receptor does insulin use? What is the mechanism of action?
Tyrosine kinase -> phosphorylates PIP3 kinase which increases intracellular Ca2+ to promote vesicles containing GLUT4 (glucose uptake) as well as stimulate glycogen, lipid and protein synthesis
What are the insulin-dependent glucose transporters and where are they found?
GLUT4 on adipose and striated muscle tissue
What are the effects of insulin
Increases: glucose transport in muscle and adipose glycogen synthesis and storage triglyceride synthesis Na+ retention (kidneys) protein synthesis (muscles) cellular reuptake of K+ and amino acids (can cause hypokalemia)
Decreases: glucagon release
Which tissues have insulin-independent glucose uptake? What are their GLUT transporters?
GLUT1- RBCs, brain, cornea
GLUT2 (bidirectional)- beta islet cells liver, kidney, small intestine
GLUT3 - brain
GLUT5 (fructose)- spermatocytes, GI tract
What are the major regulators of insulin?
Stimulated by glucose, GH, beta2 receptor action
Inhibited by glucagon, somatostatin, catecholamines, cortisol, alpha2 receptor
What is the mechanism of insulin secretion by pancreatic beta cells?
- glucose enters beta cells via GLUT2
- increased ATP is generated from glycolysis
- increased ATP closes ATP-sensitive K+ channel -> Depolarization
- Voltage-gated Ca2+ channels open -> increase intracellular Ca2+
- Exocytosis of insulin granules
What are the effects of glucagon?
Glycogenolysis, gluconeogensis in liver
lipolysis and ketone production
What is the mechanism of the glucagon receptor activation?
glucagon receptor is coupled to Gs which activates AC and converts ATP-> cAMP. Increased cAMP activates PKA which phosphorylates:
- Hormone sensitive lipase -> lipolysis
- Glycogen phosphorylase -> glycogen breakdown
- Acetyl CoA carboxylase (becomes inactivated) -> decreased fatty acid synthesis
How is glucagon regulated?
stimulated in response to hypoglycemia
inhibited by insulin, hyperglycemia, somatostatin
What is the function of CRH?
Stimulates production of POMC –> ACTH, MSH and production of beta-endorphin
What is the function of dopamine?
decreases prolactin *dopamine antagonists can cause galactorrhea from hyperprolactinemia
What is the function of GHRH?
increases GH, GnRH
What is the function of GnRH?
Increases FSH and LH
What is the function of prolactin?
Decreases GnRH
What is the function of somatostatin?
decreases GH, TSH
What is the function of TRH?
increases TSH, prolactin
What are the anterior pituitary cell types?
lactotrophs- prolactin corticotrophs- ACTH somatotrophs - GH thyrotrophs - TSH gonadotrophs - LH, FSH
What is the function of prolactin?
stimulates milk production in breast
inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH synthesis and release
Note; excessive prolactin associated with decreased libido
How is prolactin regulated?
TRH increases prolactin
prolactin tonically inhibited by dopamine from hypothalamus
prolactin inhibits own secretion via stimulation of dopamine synthesis from hypothalamus
What drugs stimulate prolactin secretion?
dopamine antagonists( most antipsychotics), estrogens, opiates, serotonin, ACh
What is the function of Growth hormone?
Stimulates secretion of IGF-1 from liver -> stimulates linear growth and muscle mass, increases insulin resistance
- decreases glucose uptake in fat, muscle -> increased blood glucose
- increases hormone sensitive lipase -> mobilize fat stores
- increases amino acid uptake -> muscle building
- chondrocytes -> linear bone growth
How is GH regulated?
GHRH stimulates pulsatile release of GH; secretion increases during exercise and sleep
Secretion inhibited by glucose and somatostatin via negative feedback by somatomedin
What are the functions of ghrelin?
produced by stomach
stimulates hunger and GH release
Ghrelin increases with sleep loss and Prader-Willi syndrome
What are the functions of leptin?
Satiety hormone produced by adipose, decreases during starvation
Sleep deprivation-> decreased leptin -> increased appetite
What are the receptors for ADH? Where are they located and what is their function?
V1 receptors on smooth muscle, myocytes, adrenals, platelets -> increase blood pressure
V2 receptors in collecting ducts -> decreases serum osmolarity and increases urine osmolarity
What is the mechanism of V1 receptors?
V1 receptors - are on smooth muscle myocytes, adrenals and platelets
Gq -> activate phospholipase C -> IP3 -> increase calcium
- vasoconstriction
- increased ACTH
- increases glycogenolysis in liver
- increases platelet aggregation
What is the mechanism of V2 receptors?
Gs -> AC -> increased cAMP -> increased aquaporin-2 inserted in principal cells -> increases urine osmolarity
How is ADH regulated?
primarily by osmoreceptors in hypothalamus -> increased ADH released when high blood osomolarity
secondarily by hypovolemia (low BP) -> increased ADH released -> increases BP
A mutation in the V2 receptor can cause what?
Nephrogenic DI
What is the function of ACTH on the adrenals?
stimulates cholesterol breakdown in zona glomerulosa via cholesterol desmolase to pregnenolone; increases synthesis of mineralocorticoids, glucocorticoids and androgens
How is ACTH regulated?
stimulated by CRH from hypothalamus and inhibited by cortisol (neg feedback)
How does 17alpha-hydroxylase deficiency affect mineralocorticoids, cortisol and sex hormone levels? How does it present?
minearalocorticoids- Increase
coritsol- Decrease
sex hormones- Decrease
Presentation
boys: pseudo-hermaphroditism (ambiguous genitalia, undescended testes)
girls: lack secondary sex characteristics
How does 21-hydroxylase deficiency affect mineralocorticoids, cortisol and sex hormone levels?
minearalocorticoids- Decrease
coritsol- Decrease
sex hormones- Increase
Presentation:
- Salt wasting in infancy (if presenting before childhood)
boys: precocious puberty
girls: virilization, ambiguous gneitalia
How does 11beta-hydroxylase deficiency affect mineralocorticoids, cortisol and sex hormone levels?
minearalocorticoids- Increase (via 11-deoxycorticosterone; low aldosterone)
coritsol- Decrease
sex hormones- Increase
Presentation:
boys:
girls: virilization
What are the clinical findings (BP, Na+, K+, labs) for 17alpha-hydroxylase deficiency?
BP: high (increased mineralocorticoids)
Na+: high (increased mineralocorticoids)
K+: low (increased mineralocorticoids)
labs: low androstenedione (decreased sex hormones)
What are the clinical findings (BP, Na+, K+, labs) for 21-hydroxylase deficiency?
BP: low (decreased mineralocorticoids)
Na+: low (decreased mineralocorticoids)
K+: high (decreased mineralocorticoids)
labs: high renin activity, high 17-hydroxyprogesterone
What are the clinical findings (BP, Na+, K+, labs) for 11beta-hydroxylase deficiency?
BP: high (increased mineralocorticoids 11-DOC)
Na+: high (increased mineralocorticoids)
K+: low (increased mineralocorticoids)
labs: low renin activity
What is cortisol bound to?
Corticosteroid-binding globulin aka transcortin; made in liver
What are the functions of cortisol?
- increase BP
- increase insulin resistance (diabetogenic)
- increase gluconeogenesis, lipolysis, porteolysis
- decrease fibroblast activity (causes striae)
- decreases inflammatory and immune responses
- decreases bone formation (decreased osteoblast activity)
How does cortisol affect BP?
- upregulates alpha1 receptors on arterioles -> increased sensitivity to E and NE
- at high concentrations cortisol can bind to mineralocorticoid receptors
How does cortisol affect inflammatory and immune responses?
decreases inflammation and immune response by:
- inhibits phospholipaseA2 -> inhibits production of PGs and LTs
- inhibits WBC adhesion -> demargination of PMNs -> increased PMNs
- inhibits PMN apoptosis
- blocks histamine release from mast cells
- reduces eosinophils
- Blocks IL-2 production
How do cortisol levels fluctuate?
Highest around noon; disturbed by stress -> prolongs secretion