Pituitary Gland Flashcards
Derived from the primitive gut by an upward extension (Rathke’s pouch) of the epithelium of primitive mouth cavity (stomodeum)
Anterior lobe (Adenohypophysis)
Devs as downward evagination of neural tube at the base of the hypothalamus (infundibulum)
True brain extension
Neural or posterior lobe (Neurohypophysis)
A derivative of neural ectoderm
Neurohypophysis
Pituitary gland location
Hypophyseal fossa in the sella tursica
Pituitary is protected by and covered by
p/b Sphenoid bone (lateral & inferior)
c/b Dura (dense CT that lines sella tursica)
Covered superiorly by diagrama sellae, a dural sheath that forms the roof of the sella
Pituitary gland anatomic relations:
Superior: Diaphragma sella
Inferior: Body of sphenoid
Lateral: Cavernous sinus
Posterior: Dorsum sellae, basilar artery, pons
S. D
I. B
L. C
P. D
Gross characteristics of pituitary
Oval, bean-shaped, symmetrical, brownish red organ
Wt. = 0.4-0.9g
Anterior lobe (80%)
Pars distalis
Pars intermedia
Pars tuberalis
Largest, site of hormone-producing cells
Pars distalis
Consists of the median eminence of tuber cinereum, the infundibular stem of the hypophyseal stalk, and infundibular process or posterior neural tube
Posterior lobe/Neurohypophysis
- reach the main body of the gland thru the diaphragma sellae
- consists of infundibular stem and the adenohypophysial tissue that is continuous w the infundibular stem
Pituitary (hypophysial) stalk
Represents the bulk of the anterior lobe in humans and receives most of its bld supply from the superior (anterior) hypophyseal portal system
Source of pituitary tropic hormones
Pars distalis
Lies between pars distalis and neural lobe
Vestigial structure in humans
Avascular & almost non-existent in humans
Pars intermedia
Elongated collection of secretory cells
Superficially envelopes that infundibular stem and extends upward as far as the basal hypothalamus
Mist vascular portion of the anterior
Pars tuberalis
Located beneath 3rd ventricle
Smol, highly vascular protrusions of the dome shaped base, designated as tuber cinereum
The floor of third ventricle is designated as infundibulum (funnel)
Median eminence
Arises in median eminence
Infundibular stem (neural stalk) of posterior lobe
Retains neural connection w the ventral diencephalon
Pars nervosa
Retains neural connection w the ventral diencephalon
Pars nervosa
Storage and secretory site for hormones; not termed as endocrine gland
Posterior lobe
Granular secretory cells that exists in two forms
Chromophils
Account for abt 80% of the chromophils and are the cellular source of prolactin and GH
Acidophils (eosinophils)
Comprise abt 20% of chromophils are source of TSG, ACTH, LH, FSH, B-lipotropic hormone (B-LPH)
Basophils
Agranular cells that are not precursors of the chromophils are now known as to have an active secretory fxn
Degranulated secretory cells
Chromophobes
The GH-secreting cells are identified as acidophilic ind std hemotoxylin prep; located in the lateral portions of the anterior lobe
Accounts for abt 50% of the adenohypophyseal cells
Somatotropes
A second but distinct acidophilic-staining cell randomly distributed in the anterior lobe is the PRL-secreting cells
Two types:
Sparsely granulated and Densely granulated
Lactotropes
Glycoprotein product are basophilic and (+) PAS stain
Least common, making up <10% of adenohypophyseal cells
Primary thyroid failure –> hypertrophy (inc gland size)
Thyrotropes
ACTH, lipotropins (LPH) and endorphins are secreted by
Basophilic cells and embryonically of intermediate lobe origin
Corticotrophs represents 15-20%
Both LH and FSH originate from basophils, whose secretory granules are abt 200nm
10-15 of the anterior pituitary cells and they are located throughout the entire anterior lobe
Gonadotropes
Acidophilic
Somatotrope
Lactotropes
Basophilic
Corticotropes
Thyrotropes
Gonadotropes
400-550nm secretory granules
Corticotropes
They are almost exclusively postganglionic sympathetic fibers that innervate BV
Neurons in anterior lobe
Nerve fibers of the neurohypophysial sys terminate in the pars nervosa, interspersed between these neurosecretory fibers are numerous glial cells called
Pituicytes
Structural support
Pituicytes
Secretory activity of the adenohypophysis depends on activation of its cells by neurohormones called releasing factors carried to the anterior lobe by a portal system of veins called
Hypophyseoportal system
Several superior hypophyseal arteries anastomose freely around the
Median prominence
Capillaries arising from these vessels penetrate into the .edian eminence forming the
Primary plexus
These capillaries arising from venules that course downward to join an extensive network of sinusoids in the anterior lobe wc constitute the
Hypophyseal system
A basic tenet of the neurovascular hypophysis is that the conc of the hypophysiotropic hormones is greater in the
hypophyseoportal bld than anu other site in the vasculature
In humans, the capillaries at the base of the hypothalamus are formed directly from branches of the superior hypophyseal arteries wc arise from
Internal carotid arteries
The crucial regulatory connection between the hypothalamus and anterior lobe is via
Hypophysial portal vessels
The intermediate lobe isn’t perfused directly by the hypophysial portal sys but is regulated by
Bioaminergic secretomotor fibers originating in the hypothalamus
Blood supply of hypothalamus
Superior and inferior hypophysial arteries - branches of the internal carotid arteries
Venous drainage of hypothalamus
Intracavernous sinuses
Those hormones that stimulate secretion of hormonally active substances by other endocrine glands, liver or tissues
Stimulate target organs which in turn exert their effects on other body organs and tissues
Tropic hormones
Exert their major effects on nonendocrine targets
Nontropic hormone
Are a family of protein hormones having considerable sequence homology
Share common Ag determinants
All have growth promoting and lactogenic activity
Growth hormone-prolactin-chorionic somatomammotropin grp
Interact w cell surface receptors and activate adenylyl cyclase and employ cAMP as intracellular messenger
Glycoprotein hormone grp
FSH LH hCG
Consists of peptides that act as hormones
Pro opiomelanocortin peptide family
ACTH LPH MSH
Both synthesize a large precursor protein that is cleaved to form a family of hormones
Intermediate-lobe cells and corticotropes of the anterior lobe
After removal of signal peptide, this prohormone is known as
POMC
pro-opiomelanocortin
In the corticotropes, it is hydrolyzed to ACTH and B-LPH plus a small amt of B-endorphin, and these subs are secreted
POMC
In intermediate-lobe cells, POMC is further hydrolyzed to
corticotropin-like intermediate lobe peptide (CLIP), y-LPH and appreciable quantities of B-endorphin
Opioid peptide that has the 5 AA residues of met-enkephalin at its amino terminal end
B-endorphin
Act as storage foe hormones made by the hypothalamic neurons
Posterior pituitary
Released in significant amounts onli during childbirth and nursing women
Oxytocin
Used to induce labor or hasten labor that us progressing normally but at a slow pace
Natural and synthetic oxytocic drugs
It causes kidneys to reabsorb more water from the forming urine thus
U decreases
BV increases
ADH
ADH increases BP by causing
Constriction of arterioles -> vasopressin
Drinking alcohol beverages
inhibits ADH secretion and results to large amt output of urine
The bodies of the cells that secrete the posterior pituitary hormones are not located in the pituitary gland itself but are large neurons called
Magnocellular neurons
Location of magnocellular neurons
supraoptic and paraventricular nuclei of hypothalamus
Lowermost portion of hypothalamus
Median eminence
Connects inferiorly w the pituitary stall
Median eminence
Small arteries penetrate into the substance of the medium eminence and then additional small vessels return to its surface, coalescing to form the
Hypothalamic-hypophysial portal BV
TRH structure
Peptide of 3 AA
GnRH structure
Sibgle chain of 10 AA
CRH structure
Single chain of 41 AA
GHIH somatostatin
Single chain 14 AA
GHRH structure
Single chain 44 AA
PIH structure
Dopamine (a catecholamine)
Could facilitate transfer of regulatory substances from the CSF to pituitary
Allow post pit pept hormones, hypothalamic releasing/inhibiting hormones or anterior pituitary tropic hormones to have access to brain via CSF
Pituitary tanycytes
No direct arterial supply but receives bld from the median eminence wc contains hypothalamic releasing and inhi hormones
Adenohypophysis
Reach theur storage and release are by their axonal transport from neuron cell bodies where they are synthesized
Posterior pituitary hormones
Synthesized in situ
Secreted in response to hypothalamic peptides that reach the anterior pit by axonall transport followed by bld transport via portal veins
Anterior pituitary hormones
Paraventricular
TRH
CRH
Arcuate
GnRH
GHRH
PIF
Anterior periventricular
GHIH (somatostatin)
Target pituitary hormones of TRH
Thyrotropin
PRL
GH (pathological)
Target pituitary hormones of GnRH
LH
FSH
GH (pathological)
Target pituitary hormones of CRH
Adrenocorticotropin
B- and y-Lipotropin
B-endorphins
Target pituitary hormones of GHIH
GH
PRL
Thyrotropin
Adrenocorticotropin (pathological)
Target pituitary hormones of PIH
PRL
Thyrotropin
GH (pathological)
Characteristics of hypothalamic releasing hormones
- Secretion of pulses
- Sp plasma mem receptors
- Tranduction of signals thru Ca, mem phospholipid prod, cAMP as secondary messengers
- Stim of release of stored target anterior pituitary hormones via exocytosis
- Stim of synthesis of target ant pit hormones at transcriptional lvl
- Modification of biological activity of target ant pit hormones by post-translational effects such as glycosylation
- Stimulation of hyperplasia and hypertrophy of target cells
- Modulation of effects by up- or down-regulation of their own receptors
Peripheral gland hormones or subs that arise from tissue met cab exert feedback ctrl on both hypothalamus and ant pit gland
Long loop feedback
Usually (-)
Occasionally (+)
Neg fb by tropic hormones themselves thru effects on synthesis or discharge of related hypothalamic releasing or inhibiting hormones
Short loop
Hypothalamic releasing hormones may even inhibit their own synthesis by stimulating the discharge of a paired hypothalamic inhibiting hormone
Ultrashort LF
Nt bet 2 cells or transport of releasing hormone via pit tanycytes to CSF then to hypothalamus
Central pt of hypothalamic pituitary-peripheral gland axis
Anterior pituitary gland
Afferent impulse to the hypothalamus
Norepinephrine
Acetylcholine
Serotonin
Efferent impulses to median eminence
Dopamine Acetylcholine y-aminobutyric acid GABA Opioid peptide B endorphins
Synthesized by the acidophils of the anterior lobe and is stored in v large amts in pituitary gland
4-10% of wet wt of pituitary gland wc is equivalent to 5-15mg
GH
GH has been synthesized in bacteria using recombinant DNA techniques, what is its structure?
Single (lyk ü)
Unbranched polypeptide chain cont 191 AA residues
Like all other pituitary hormones, GH is secreted episodically in periods of
20-30 mins
Large diurnal fluctuations
A regular nocturnal peak in GH secretion occury
1-2 hrs after onset of deep sleep
Correlates w stage 3 or 4 slow wave sleep
Principal GH in humans has approx MW of
22K GH w 2 disulfide bridges and 191 AA residues
90% pit
10% lacks AA
The basal growth hormone lvl measure by immunoassay in adult is normally
<3ng/mL
GH is bound to
2 proteins in plasma
The half life of circulating GH in humans is
6-20 mins
Daily GH output
0.2-1.0mg/d in adults
Release of GH is mediated by what?
Thus a-adrenergic, dopaminergic, serotoninergic agonists and B-adrenergic antagonists all stimulate GH release
Monoaminergic and serotoninergic pathways
Stimulate GH secretion
Bromocriptine
Enkephalins
Endorphins
Opiates
A dopamine agonist
Bromocriptine
Potent stimulus of GH secretion as are pharmacologic doses of glucagon and vasopressin
Insulin-induced hypoglycemia
Physiologic stimuli
- Hypoglycemia
- Increased plasma conc of AA (arg, leu, lys, trp, 5-hydroxytryptophan)
- Decreased FFA conc
- Estrogen stim GH syn and sec
GH can inhibit its own secretion bia a short-FL that operates between
Anterior lobe and median eminence
A tetradecapeptide (14 AA residues) that has been chemically synthesized
Somatostatin
A product of parvicellular neurosecretory neurons that terminate in median eminence and produce hypophysiotropic hormones
Somatostatin
Blocks insulin secretion, also glucagon, gastrin, and intestinal absorption of glucose
Hypogly
Somatostatin
Decrease GH secretion but their predominant effect is the interference w the metabolic actions of GH
Glucocorticoids
Stimulate GH secretion
- decreased bld glucose
- decreased bld FFA
- starvation, fasting, protein def
- trauma, stress, excitement
- exercise
- testosterone, estrogen
- deep sleep (stage 2 and 5)
Inhibit GH secretion
- inc bld glucose
- inc bld FFA
- aging
- obesity
- GHIH (somatostatin)
- GH (exogenous)
- somatomedins (insulin like GF)
Stimuli that increase secretion GH
Def of energy substrate
- hypogly
- 2-deoxyglucose
- exercise
- fasting
Increase in circulating lvls of certain AA
- protein meal
- infusion of Arg and some other AA
Glucagon
Stressful stumuli (huhuhu but y am i not getting any taller jk, fat lang)
- pyrogen
- lys vasopressin
- psychological stress ugh
Going to sleep ooooooohhh
L-dopa and a-adrenergic agonists that penetrate brain
Apomorphine and other dopamine receptor agonists
Estrogens and androgens
Stimuli yhat decrease GH secretion
REM sleep Glucose Cortisol FFA Medroxyprogesterone GH
Synthesized mainly in liver
Also termed insulin-like growth (IGF)
Effects of GH on skeletal growth are mediated by a family of polypeptides called
Somatomedins
Also necessary for normal osteogenesis
Thyroid hormone and insulin
GH causes the liver to form several smol proteins called
Somatomedins
- most important is: somatomedin C
Has a potent effect of increasing all aspects of bone growth
Somatomedin C
Stimulates proliferation of chondrocytes and appearance of osteoblasts
GH thru somatomedin
- the increase in thickness of epiphysial (cartilaginous) end-plate accounts for the increase in linear skeletal growth
After epiphysial fusion, bone length can no longer be increased by GH, but
Bone thickening can occur thru periosteal growth. It is this growth that accounts for the changes seen in hypersomatotropism (acromegaly)
GH has predominantly what effect on skeletal and cardiac muscle, where it stimulates the synthesis of protein, RNA, DNA
Anabolic effects (CHON MET)
GH reduces circulating lvls of AA and urea (promotes nitrogen retention) wc accounts for the term
Positive nitrogen balance
Urinary urea conc also decreases
GH overall effect on adipose tissue
Dec: TAGs
Inc: plasma FAs and glycerol
Catabolic effect (FAT MET)
GH increases hepatic oxidation of FA to the
Ketone bodies
Acetoacetate
B-hydroxybutyrate
GH is a diabetogenic hormone. Because of its anti-insulin effect, GH has the tendency to cause
Hyperglycemia
GH can produce an insulin-resistance diabetes mellitus primarily because of its
Lipolytic effect
These can antagonize the effect of insulin to promote glucose uptake by skeletal muscle and adipose
FFAs
Excess acetyl coenzyme-A production favors
Gluconeogenesis
- bcs pyruvate carboxylase requires acetyl-CoA to form oxaloacetate from pyruvate
Rate-limiting factor in pyruvate kinase
Oxaloacetate
Do u remember ted mosby’s statement: “it’s funny how you just
…find things”
But really, they never tell you that either you keep it and hold it dear, or you lose it because of being too preoccupied by a lot of things going on in your life. It should be “isn’t it funny how you just find things, and wonder if you’ll have to let it go or hold on to it up to the end.” Ok so random
acetyl-CoA inhibits glycolysis by inhibition of
PK
FFAs stimulate hepatic glucose synthesis mainly via the stimulation of
fructose biphosphatase
What are inhibited by FFAs wc bld glycolysis and gluconeogenesis favors
PK and phosphofructokinase
Blocks glycolysis at the phosphofructokinase step
Citrate
Because of its anti-insulin effect, GH inhibits glucose transport in
Adipose tissue
Bcs adipose tissue requires glucose for TAG synthesis, GH antagonizes
Insulin-stimulated lipogenesis
Mineral metabolism: GH promotes renal absorption of
Ca
Ph
Na
GH promotes a positive Ca, Mg and Ph balance and causes the retention of
Na
K
Cl
Essential for postnatal growth and normal carbs, lipid, nitrogen, mineral met
GH
The growth related effects are primarily mediated by
IGF-I
- family of insulin like gene
- similar to proinsulin
Elevated in newborns
Plasma GH
Rise during childhood, reaching a peak at 13-17 years old
IGF-I
Constant throughout postnatal growth
IGF-II
Growth spurt that occurs at puberty is d/t protein anabolic effect of
Androgens and secretion of adrenal androgens, increases in both sexes
Tx of these increases GH responses to stimuli s/a insulin and arginine
Estrogen and androgens
Sex steroids also increase plasma IGF-I but cant inc in GH deficiency
Thus, it appears that the sex hormones produce an increase in amplitude of the spikes in GH secretion that increases IGF-I secretion and cause growth
Terminate growth by causing epiphysis to fuse long bones (epiphysial closure)
Estrogen
- bcs linear growth ceases
- this is y pt w sexual precocity are apt to be dwarfed
Why do men before puberty tend to be tall bcs estrogen prodxn is decreased and epiphysis remain open so that some growth continues past the normal age of puberty
Men were castrated
Necessary for a completely normal rate of growth
Thyroid hormones
Period wherein accelerated growth is partly a continuation of the fetal growth pd
First period
At the time of puberty, this is d/t GH, androgens, estrogens and cessation of growth is due in large part to closure of the epiphysis by estrogens
Second growth spurt
During infancy, growth isn’t a continuous process but is
Episodic or saltatory
Increases in length of human infants of how many cm in a few days are separated by pds of 2-63 days during wc no measurable growth can be detected
0.5-2.5cm
Inc GH
Dec somatomedin
Growth retardation
- kwashiorkor
- African pygmy (resistant to action of GH; both normal, decreased GH receptors)
GH overproduction in adolescence
Excessive growth of long bones
Gigantism
8ft
Excess GH secretion in adulthood (after epiphysial plates of long bones have fused, causes cartilage area growth persists)
Acromegaly
- facial features
- underbite (prognathism)
- prominent brow
- enlarged hands and feet
- soft tissue hypertrophy (e.g cardiomegaly, hepatosplenomegaly, renomegaly)
Decreased GH secretion in immature persons lead to
Stunted growth
Dwarfism
Stunted growth or Dwarfism is accompanied by
Sexual immaturity
Hypothyroidism
Adrenal sufficiency
Overall lack of anterior pituitary hormones (panhypopituitarism) or isolated genetic deficiency
GH def
Rare in adults
Clinical manifestations: impaired hair growth and tendency toward fasting hypoglycemia
Selective GH def
Tx of choice for hypersomatotropism
Selective surgical extirpation of pituitary adenoma w/o damage to other pituitary fxns
Effective in suppressing, but not normalizing, GH lvls in most acromegalic pt
This tends to stimulate GH sec in normal indiv
Bromocriptine
Disorders associated w GH def can be treated with
HGH
Lactogenic hormone, mammotropic and galactopoietic hormone
Prolactin
Synthesized in the pituitary acidophils
A single peptide chain containing 198 AA residues
Doesn’t regulate the fxn of a secondary endocrine gland in humans
Prolactin
A putative releasing hormone for PRL
Hasn’t been identified or chemically synthesized however one of these releasing factors is TRH (vauses TSH release)
PRF
Its secretion increases abt 1 hr after onset of sleep
And increases continuous throughout sleep pd
Nocturnal peak occurs later than that for GH
PRL
Enhanced by exercise or stress ooof example surgery under gen anes, MI, repeated veni hahahaha aww
PRL
- inc by 8th wk preg
- peak on 38th wk preg
Elevated in those w primary hypothyroidism who believed to have high TRH in hypophyseoportal circ
Serum PRL
Stimulate PRL secretion
Dopamine antagonist (phenothiazine & tranquilizers)
Adrenergic blockers
Serotonin agonists
What interferes w portal circ to pituitary gland that also cause PRL release
Pituitary stalk secretion and lesion
Physiologically most important PIF
Secreted into hypophysial portal vessels
Dopamine
Block PRL secretion
Serotonin antagonists abd dopamine agonists (bromocriptine)
Administered during postpartum pd reduces PRL sec to nonlactating lvls abd terminates lactation
Bromocriptine
Not a gonadotropic hormone in women
Doesn’t hav important role in maintaining secretory fxn of corpus luteum
PRL
Immediately following preg, PRL stimulates galactocyltransferase activity, leading to synthesis of
Lactose
High PRL in serum is associated w
suppressed LH and anovulation
- accounts for absence of menses (amenorrhea) during postpartum lactation
With continued nursing,
FSH rise
LH remain low
In early postpartum pd,
FSH and LH both low
Not rare but frequently in undiagnosed bcs galactorrhea occurs in only abt 30% of cases
Hyperprolactinemia
Hyperprolactinemia in women and men
Women: infertility and amenorrhea
Men: a cause of impotenxe and decreased libido
PRL hypersecretion tx
Bromocriptine
A dopamine agonist that lowers PRL lvls and usually restores normal gonadal fxn
Bromocriptine
Causes vasoconstriction of arterioles and increase in systemic BP
Vasopressin
Biologically active form of ADH in humans
Arginine vasopressin
A hypothalamic hormone synthesized in the supraoptic and paraventricular nuclei in ventral diencephalon
ADH or vasopressin
What synthesize, store and secrete ADH
Unmyelinated neurosecretory neurons
Terminates in pars nervosa or posterior lobe of the pituitary gland (Neurohypophysis)
Supraopticohypophyseal tract
Peptidergic neurons that conduct action potentials
Neurosecretory neurons
The hypothalamic nuclei that synthesize and secrete ADH are collectively called
Magnocellular neurosecretory neurons
Polypeptide specifically octa or nonapeptide w a molecular wt of 1000
ADH
If 2 cysteine residues are considered as a single cysteine residue, ADH is an
Octapeptide
If 2 cysteine residues are numbered individually
Nonapeptide
Physiologic carrier proteins for intraneural transport of ADH and are released into the circulation w neurosecretory products (ADH oxytocin) without being bound to the hormone
Neurophysins
Biological half life of ADH
16-20 mins
Major stimuli for ADH secretion
Hyperosmolality and effective circulating BV depletion
Prime determinant of ADH secretion and most common physiologic factor altering the osmolality of bld is water depletion or water excess
Hyperosmolality
1-2% increase in plasma osmolality
Located in the anterior hypothalamus and are distinct from the cells that sybthesize ADH
Osmoreceptors
- lowest threshold (most sensitive) to changes in osmolal conc of plasmA
- stimulation causes reflex secretion of ADH
Cross tha BBB relatively slowly
Are potent stimulators of ADH release
Na and mannitol
Less potent stimulus for ADH prod and secretion that hypernat for same lvl of osmolality
Hyperglycemia
Hyperglycemia associated w insulin def
Uncontrolled DM
Decreased effective circulating BV
More dominant stimulus to ADH release that js hyperosmolality
Hypovolemia
Will evoke ADH release
10-25% decrease in BV
Sufficient to cause release enough ADH to participate in immediate regulation of BP
10% decrease in BV
May cause ADH release
Contraction of BV without an alteration in the tonicity of body fluids
Baroreceptors. Hemodynamic changes (changes in BV, BP or both) are mediated by
Autonomic (parasympathetic) afferents
- they arise in pressure (vol) - sensitive receptors in the atria, aortic arch, carotid sinus, great veins and pulmonary vessels and traject via the vagal and glossopharyngeal nerves to primary synapses in the nucleus tractus solitarius in the brain stem
Primary mediators of vol effects on ADH secretion
Low pressure (stretch) receptors
Inhibits ADH-producing cells
Inc BP
Reduces firing frequency of baroreceptors, causing stimulation of ADH syn and release
Decreased BP
Can be a dominant stimulus but isn’t the physiologic regulator of ADH secretion
Baroregulation of ADH secretion
Expansion of intracellular vol of osmoreceptors secondary to hyposmolality of ECF
Inhibits ADH secretion
What contributes to hyposmolality of ECF
Water ingestion
Inhibits ADH release
Increased arterial pressure secondary to vascular of ECF volume expansion
Also inc tension in left atrial wall, great veins sec to inc intrathoracic BV dt hypervolemia, a reclining position, neg pressure breathing and water immersion up to neck
Also recumbent, inc central BV leads to atrial pressure
Also sleep, prod of a conc urine dt redxn of BP
Stimuli
Postive pressure breathing
Physiologic:
Hyperosmolality
Upright
Exercise
Patho:
Dec BV NS Cirrhosis CHF Hypothalamic dse Pulmonary dis CNS dis Hypothyroidism Na def Vasovagal rxn lipong Pain nausea emotional stress haixt DM
Pharmacologic:
Li Morphine high dose Barbiturates Nicotine Ache Diuretics Isoproterenol Nitroprusside Trimethaphan Histamine Bradykinin Angio II Insulin 2-deoxy-D-glucose Cholinergic B-adrenergic agonists
Inhibitors
Neg PB
Hyposmolality
Recumbent positio
DI
Inc BP
Hyposmolality
SIADH
Norepi Ethanol Caffeine Anticholinergic CO2 Marphine low dose Phenytoin Li
Major site of ADH action
Receptor in basolateral membrane of principal cells of the cortical and medullary collecting ducts where ADH increases that permeability to water
ADH w its effect on increased water reabsorption
Leads to prodxn of urine w a decreased vol and increased osmolality
ADH stim ACTH from the
Anterior lobe of pituitary gland
Plays a role in ctrl aldosterone secretion
ACTH
Excessive or inappropriate secretion of ADH from posterior lobe or from an ectopic (nonhypothalamic) source, s/a malignant tumor – bronchogenic carcinoma
SIADH
Water retention occurs leading to
Expansion of bld and ECF volumes
Present dt suppression of aldosterone secretion
Hypernatriuria
Hyponatremia
SIADH tx
Demeclocycline
A tetracycline that blocks effect of ADH
Demeclocycline
May cause nephrogenic diabetes
Demeclocycline
Li carbonated
Amphotericin B
Methoxyflurane
Complete or partial faulure to either ADH sec or renal response to ADH
DI
Characterized by a decrease renal watee reabsorption by collecting ducts
DI
Dec watee reabsorption = diuresis of dilute U
3-20L/day
Polyuria
U output is directly related to the volume of water delivered to the coll ducts
Nephrogenic diabetes
Thirst and inc qater intake
Polydipsia
Diagnosis of diabetes insipidus in a polyuric pt is confirmed by
Insignificant diuresis or prodxn of hypertonic urine following water restriction by hypertonic saline infusions
Response to injected vasopressin
Neurogenic DI
Lack response to vasopressin
Nephrogenic DI
Neurogenic DI hormonal therapy
ADH administration as vasopressin tannate or nasal lysine vasopressin
Neurogenic DI non-hormonal therapy
Oral hypoglycemia agents (chlorpropamide)
Thiazide diuretics w Na restriction
Carbamazepine
Clofibrate
Nephrogenic DI tx
Thiazide
Inhibits Na reabsorption in diluting segment (ALH)
Thiazide
A nonapeptide
Synthesized in cell bodies of peptidergic neurons of magnocellular neurosecretory sya
Mainly in paraventricular nuclei of hypothalamus
Stored un posterior lobe same w ADH
Oxytocin
Brought abt by stimulation of cholinergic nerve fibers
Oxytocin secretion
Reflex (milk letdown or ejection) secretion of oxytocin into bldstream and to milk release ff a latent pd of
30-60 seconds
Excitation of adrenergic fibers to the hypothalamus
Inhibits peptide release (oxytocin)
What else inhibits oxytocin secretion?
- activation of sympa w concomitant release of norepi and epi
What inhi oxytocin release?
enkephalins
Inhibits endogenous oxytocin release resulting in reduced myometrial contractility
Ethanol
