Exam 2 Material Flashcards
The endocrine system provides ____ of many tissues
broadcast regulation
The specificity of the endocrine system is due to:
receptors
Compared to the nervous system, the responses of the endocrine system are:
slower but longer lasting
List the 3 functions of hormones:
- maintenance of homeostasis
- growth and differentiation
- reproduction
Endocrine organs can be divided into what two categories?
- major endocrine glands
- organs w/ endocrine cells
Primary function is to make a hormone and release it when the stimuli are present
major endocrine organ
organs that happen to have endocrine cells allowing them to release a hormone although their primary fxn is NOT endocrine regulation
organs containing endocrine cells
List specialized endocrine glands (major endocrine organs)
- parathyroid gland
- thyroid gland
- pituitary gland
- adrenal gland
- pineal gland
List some organs that contain endocrine cells but their primary function is not endocrine regulation:
- hypothalamus
- skin
- adipose tissue
- thymus
- heart
- liver
- stomach
- pancreas
- small intestine
- kidneys
- gonads
A hormone that causes secretion of a hormone by an endocrine gland:
tropic hormone
How do we classify hormones?
based on their structure
What are the 3 classifications of hormones?
- proteins or polypeptides
- steroids
- tyrosine derivatives
Describe the time period in which protein and polypeptide hormones are made and released:
made in advance and stored in vesicles until signal for release
Protein and polypeptide hormones are synthesized first as ____.
Preprohormone
The preprohormone will be converted into:
prohormone
In protein and polypeptide hormones what is packed into vesicles of the endocrine cell prior secretion?
prohormone
After the prohormone gets cleaved, it is now:
active hormone
Mnemonic for protein and polypeptide hormones:
Protein/Polypeptide/Pre & Pro hormones (Everything with P’s)
in addition to the active hormone, what gets released in when the prohormone gets cleaved?
inactive fragment
What is the first thing that gets cleaved from preproinsulin?
signal peptide
After the signal peptide is cleaved from preproinsulin, what occurs?
protein folding
Following cleavage of the signal peptide from preproinsulin and protein folding, what results:
Proinsulin
Proinsulin gets stored in:
vesicles
Upon receiving a a signal for release into the bloodstream, what gets cleaved from proinsulin to convert to active insulin?
C-peptide
Along with insulin release into the bloodstream, what also gets released?
C-peptide
If you wanted to measure someones baseline endogenous production and release of insulin, you could measure the:
c-peptide levels in the blood stream
protein and polypeptide hormones are often made as an:
inactive precurser
The inactive precursor of protein and polypeptide hormones:
preprohormone
What does the signal peptide in insulin serve as?
A marker that tells the cell that insulin needs to undergo exocytosis
Where are the receptors located for protein/polypeptide hormones?
In the plasma membrane
Describe the time period in which steroid hormones are made and released:
Made and released on demand
Where are the receptors located for steroid hormones?
Inside the cell
Why are steroid hormone receptors located inside the cell?
steroid hormones can cross the plasma membrane and bind to receptors inside target cells
Hormones from the hypothalamus, anterior pituitary, posterior pituitary, and pancreas:
protein and polypeptide hormones
Hormones from the adrenal cortex, ovaries and testes:
steroid
Steroid hormones are synthesized from (derivatives of):
cholesterol
What are two hormones that are derived from cholesterol that are STRUCTURALLY very similar?
Aldosterone & Cortisol
DHEA, Androstenedione, testosterone, and estradiol are all steroid hormones involved in:
reproduction
What determines what steroid hormone will be produced from the precursor cholesterol?
compliment of enzymes present
Describe the time period in which amine hormones are made and released:
made early and stored until secreted
Amine hormones are derived from:
amino acid tyrosine
Thyroid hormone, Noepinephrine and Epinephrine are all:
amine hormones
Epinephrine and norepinephrine are both:
adrenal medullary neurohormones
Thyroid hormone binds to the protein:
thyroglobulin
Epinephrine and norepinephrine are stored in vesicles and released via:
exocytosis
structurally what is the difference between T3 and T4?
the # of Iodide atoms attached
What is a precursor to epinephrine and norepinephrine?
Dopamine
Hormones released into circulation can either circulate ____ or ____.
Freely or with binding proteins
The majority of ____, ____, and _____ hormones circulate in their free form.
amines, peptides and proteins
What is the exception to most amines circulating in their free form? Why?
Thyroid hormones because its double ring structure makes it soluble enough to where it needs help getting through the plasma
Describe the solubility of amines, peptides/protein hormones:
water soluble
_____ & _____ circulate bound to specific transport proteins
steroid and thyroid hormones
Some binding proteins are specific for a given hormone but some plasma proteins such as ____ & ____ can bind to many hormones
globulin & albumin
What is a shuttle bus found in the plasma (plasma protein) that transports a lot of things such as lipid soluble hormones and fatty acids:
albumin
Most binding proteins are synthesized in the:
liver
Patients with a compromised liver may show signs of:
endocrine deficiencies
Why might a patient with a comprised liver show endocrine deficiencies?
Because most binding proteins are synthesized in the liver and if you can’t make enough binding proteins you can’t get enough hormone into the blood
It is always the ____ version of the hormone that binds to the receptors and affect the target cell.
Free version (binding protein stays in blood vessel)
The constitutive level of plasma hormones
basal level
The stimulated level of plasma hormones
peak levels
The variable patterns of hormone release (oscillation) is determined by the interaction and integration of multiple control mechanisms which include: (4)
hormonal, neural, nutritional, and environmental
When a hormone is constantly secreted in small amounts all of the time:
tonic release
Hormone fluctuations that happen dependent on the time of day:
circadian rhythm
Give an example of a hormone that follows circadian rhythm release:
cortisol
When does cortisol spike?
early morning hours
What can work in addition to circadian rhythm release to regulate the release of hormones?
stimuli
Growth hormone is secreted during sleep following a circadian rhythm release pattern but also displays:
pulsatile secretion
Secreted in pulses (secretes, stops, secretes, stops)
pulsatile secretions
The location of the hormone receptor depends on the ____ properties of the hormone
chemical
The chemical properties of the hormone that determine the location of the hormone receptor:
lipophilic/lipophobic
Ligand/receptor binding demonstrates:
- specificity
- affinity
- saturation
Which classes of hormones bind to plasma membrane receptors?
polypeptide/protein and amine hormones
What amine hormone does not bind to plasma membrane receptors (exception)
thyroid hormone
Which class of hormones binds to nuclear receptors?
steroids hormones + thyroid hormone
which amine hormones bind to plasma membrane receptors?
epinephrine and norepinephrine
What type of receptors would the following hormones bind to and why?
Glucagon
Angiotensin
GnRH
SS
GHRH
FSH
TSH
ACTH
Plasma membrane receptor - they are peptide and protein hormones
In general, many of the receptors that protein/peptide hormones and amine hormones bind to in the PM are:
GPCR
Involved in turning on or off a protein that is already in the cell
plasma membrane receptors
What class of hormone receptors are involved in causing a change in gene expression to get a biological response
nuclear receptors
Class of hormone receptors involved in making new proteins
nuclear receptors
Thyroid hormone and steroid hormones bind to receptors in the:
cytoplasm or nucleus
once the steroid hormone or thyroid hormone binds to the receptor located in the nucleus or cytoplasm what occurs next?
transformation of receptor to expose DNA-binding domain
Following binding of the steroid or thyroid hormone to the receptor and transformation of the receptor to expose the DNA binding domain, what next occurs?
Binding to enhancer like element in DNA
Examples of plasma membrane hormone receptors:
- g-protein coupled receptor
- tyrosine kinase
Why do plasma membrane hormone receptor numbers vary greatly in different target tissues?
this provides a way to achieve specific tissue activation
What are two examples of plasma membrane hormone receptors that are more widely distributed?
- thyroid hormone receptors
- insulin receptors
Why are thyroid hormone receptors and insulin receptors more widely distributed?
Because there actions are something that most cells participate in
How do IGF-1 and insulin work?
By activating a tyrosine kinase receptor
If it is a plasma membrane receptor, generally it will activate or inhibit _____ to _____.
an existing protein to yield a faster response
Where are nuclear hormone receptors located?
cytoplasm or nucleus
Nuclear hormone receptors typically leads to:
formation of new proteins
Nuclear hormone receptors all act to:
increase or decrease gene expression
In a nuclear hormone receptor, the hormone receptor complex binds to a _______, in the _____ region of the gene which leads to either activation or repression of _____.
hormone responsive element; promotor region; gene trasncription
Because nuclear hormone receptors binding a hormone leads to the formation of a new protein, describe the timeline involved:
It takes a little bit longer to get the response and the response will last a bit longer
Hormones that bind to nuclear receptors (thyroid hormone & steroid hormones) undergo _____ to get through the plasma membrane
simple diffusion
The body often releases multiple hormones…
at the same time
What are the effects of combined hormone actions? (4)
- antagonism
- additive
- synergistic
- permissiveness
When two hormones change one variable in opposite directions:
antagonism
When the response of a hormone is equal to the two portions that each hormone provides (2+3=5)
additive
Ramps of up the systems response when there is a present of more than one hormone- the combined response is greater than each would give individually (2+3=10)
synergistic
The presence of one hormone is necessary for another hormone’s maximum effect:
permissiveness
Determine which hormone interaction is being described:
Parathyroid increases plasma calcium levels; calcitonin decreases plasma calcium levels:
antagonistic
Determine which hormone interaction is being described:
Glucagon, cortisol and epinephrine all increase blood glucose more than the sum of their individual effects:
synergistic
Determine which hormone interaction is being described:
Thyroid hormone causes expression of B adrenergic receptors in bronchiolar smooth muscle:
permissiveness
What determines whether the negative feedback will be short loop or long loop?
The location of the hormone that acts as negative feedback in the system
When the last hormone in the pathway inhibits the system upstream:
long loops negative feedback
When an intermediate hormone in the pathway inhibits the system upstream:
short loop negative feedback
Feedback where the hormonal product or an intermediate hormone enhances the hormone secretion
positive feedback
Causes an endocrine gland to secrete a hormone:
tropic hormone
Stabilizes the system and prevents oversecretion:
negative feedback
Hormones that have other endocrine glands as their targets:
tropic hormones
A tropic hormone that from the hypothalamus that acts on the anterior pituitary to release TSH:
TRH
TRH comes from
Hypothalamus
TRH acts on the:
anterior pituitary
TSH (thyroid stimulating hormone) is released from the:
anterior pituitary
TSH is release from the anterior and acts on the:
thyroid gland
In the regulation of thyroid hormone: A stimulation causes the hypothalamus to secrete _____ which acts on ____.
thyrotropin releasing hormone (TRH); anterior pituitary
In the regulation of thyroid hormone: ______ cells in the anterior pituitary release _____.
thyrotropic cells; thyroid stimulating hormone (TSH)
In the regulation of thyroid hormone: TSH stimulates _____cells of the thyroid gland to release ______
follicular cells; thyroid hormone
Thyroid hormone produces effects in the body that include:
- increase in metabolic activity
- Increase in body temperature
In the regulation of thyroid hormone: Thyroid stimulates target cells to increase _____ activities, resulting in an increase in basal body temperature
metabolic activities
In the regulation of thyroid hormone: Increased body temperature is detected by the hypothalamus and the secretion of ____ by the hypothalamus is ____.
TRH; inhibited
In the regulation of thyroid hormone: Thyroid hormone also blocks TRH receptors on thyrotropic cell, inhibiting synthesis and release of ____. Both effects indirectly dampen ____ production in the thyroid.
TSH; TH
Thyroid hormone working to negatively feedback is an example of:
long loop negative feedback
If hormone levels are NOT kept in balance via negative feedback mechanisms, what occurs?
endocrine disorders/ pathologies
Enlargement of the thyroid due to increased of decreased thyroid hormone levels:
thyroid goiter
Disease characterized by increased cortisol levels:
Cushing’s Disease
Abnormality in the last endocrine organ secreting the hormone leading to either hypo- or hyper-secretion:
primary endocrine disorder
List the causes of primary hyposecretion:
- partial destruction of the gland
- dietary deficiency
- Enzyme deficiency required for hormone synthesis
List the causes of primary hypersecretion:
endocrine gland tumor
Abnormality in tropic hormone leading to either hypo- or hyper-secretion
secondary endocrine disorder
List the causes of secondary hypersecretion:
A lack of sufficient tropic hormone
List the causes of secondary hypersecretion:
A tumor (either in an endocrine gland that secretes tropic hormones or in a non-endocrine tissue that secretes hormones)
When you see an endocrine hormone disturbance as a result of cancer:
paraneoplastic endocrine syndrome
When you think of primary endocrine dysfunction, you should think:
LAST GLAND IN PATHWAY
Type of diagnostic endocrine function test in which you give something to make hormone levels go up to see if the hormone levels actually go up:
Type of diagnostic endocrine function test in which you give something to inhibit the hormone levels in question and look to see if that actually works:
stimulation test
supression test
Suppression test would be used to detect what type of endocrine dysfunction?
hyperfunction
List the types of diagnostic test of endocrine function: (7)
- Plasma hormone levels
- Autoantibodies
- Urine hormone/ hormone metabolite levels
- Stimulation tests by admin of topic or stimulating hormone
- Suppression when hyperfunction of endocrine organ is suspected
- Measurement of hormone receptor presence, number and affinity
- Imaging
Stimulation test work by administering a ____ hormone.
tropic or stimulating
An example of measuring hormone receptor presence as an endocrine diagnostic function test:
estrogen receptors in breast tumors
What autoantibodies might be tested when doing diagnostic tests of endocrine function?
- Hashimoto thyroiditis
- Type I DM
- Graves Disease
- Addison disease
- Autoimmune hypothyroidism
Glucagon, angiotensin, Gonadotropin releasing hormone (GnRH), Somatostatin (SS), Growth hormone releasing hormone (GHRH), follicle stimulating hormone (FSH), Lutenizing hormone (LH), Thyroid stimulating hormone (TSH), Adrenocorticoptropin hormone (ACTH) are all _____ hormones.
When are they made?
polypeptide/protein hormone
made in advance & stored
Epinephrine and Norepinephrine are both ____ hormones.
When are they made?
amine hormones
made in advance and stored
Thyroid hormone is a ____ hormone.
When is it made?
EXCEPTION:
amine hormone
made in advance and stored (does bind to nuclear receptor though)
Aldosterone, Crotisole, Estradiol and testosterone (mineralcorticoids, glucocorticoids and androgens) are all _____ hormones.
When are they made?
steroid hormones
made on demand
List things that would cause stimulation of growth hormone release
growth hormone releasing hormone, dopamine, catecholamines (in times of stress and exercise), excitatory amino acids, thyroid , fasting (hypoglycemia)
List things that would cause inhibition of growth hormone release
Somatostatin (SS), IGF-1 (due to negative feedback), Glucose (at high levels- hyperglycemia), and free fatty acids
GHRH, Dopamine, Catecholamines, Excitatory amino acids, and thyroid hormone would cause _____ of growth hormone release:
stimulation
Somatostatin, IGF-1, Glucose, and FFA would cause ____ of growth hormone release:
inhibition
portion of the pituitary that is truly filled with endocrine cells- a true endocrine gland:
Adenohypophysis
adenohypophysis is referring to what portion of the pituitary gland?
anterior pituitary
portion of the pituitary that contains axons terminals of hypothalamic neurons:
Neurohypophysis
Neurohypophysis is referring to what portion of the pituitary gland?
posterior pituitary
The pituitary gland is located in the _____ ventral to the ____.
sella turcica; diaphragma sella
List the hormones secreted by the anterior pituitary: (6)
- FSH
- LH
- Adrenocorticotropin (ACTH)
- TSH
- Prolactin
- Growth hormone
List the hormones secreted by the posterior pituitary:
- antidiuretic hormone/vasopressin (ADH)
- oxytocin
The pituitary gland secretes _____ hormones:
peptide
What are the most prevalent cells in the anterior pituitary and what do they secrete?
somatotrophs; GH
What percentage of cells do somatotrophs comprise in the anterior pituitary?
30-40%
What is the second most prevalent type of cell in the anterior pituitary and what do they secrete?
Corticotrophs; ACTH
What percentage of cells do corticotrophs comprise in the anterior pituitary?
20%
Aside from corticotrophs and somatotrophs what other types of cells make up the anterior pituitary and what do they secrete?
Thyrotrophs-TSH
Gonadotrophs- LH & FSH
Mammotrophs- prolactin
Adenomas involving somatotropic cells can cause ____ if occurring in children before closure of the long bones epiphyseal plates or _____ in adults with musculoskeletal, neurologic, and other medical consequences.
gigantism; acromegaly
Benign tumors of epithelial cells that make hormones:
Adenoma
Endocrine cells are derived from:
epithelial cells
If a benign tumor is involved in somatotropic cells, this would cause over secretion of:
growth hormone
Majority of cells in the anterior pituitary are devoted to making ____ & ____.
GH & ACTH
Neurons in the hypothalamus synthesize and secrete _______ hormones that control endocrine cells in the ____.
hypothalamic releasing and inhibiting; anterior pituitary
The hypothalamic hormones are released into the ____ in the ____ (in the hypothalamus)
primary capillary plexus; median eminence
responsible for carrying the hypothalamic hormones to the sinuses of the anterior pituitary:
hypothalamic-hypophyseal portal blood vessels
The hypothalamic-hypophyseal portal blood vessels carry the hypothalamic hormones to the ____ of the anterior pituitary
sinuses
Regulation of Anterior Pituitary Secretion
- the _____ releases hormones that enter into the blood
- the hormones travel through the _____.
- the hormones continue down through the capillary bed to the ____ where they can leave the blood and regulate the activity of endocrine cells
- hypothalamus
- primary capillary plexus
- sinus
Two capillary beds in series
portal system
The hypothalamic-hypophyseal portal vessel is comprised of:
primary capillary plexus+ sinus
The hypothalamic-hypophyseal portal vessel allows for:
communication from hypothalamus to anterior pituitary
Where do releasing hormones come from?
hypothalamus
Where do stimulating hormones come from?
anterior pituitary
The hypothalamic regulatory hormones bind to _____ in the various endocrine cells of the anterior pituitary
G-protein coupled receptors
Following the binding of the hypothalamic hormones to the g-protein coupled receptors in the anterior pituitary, what will stimulate or inhibit anterior pituitary hormone secretion?
second messengers (examples= cAMP via adenylate cyclase, IP3, and DAG vis phospholipase C)
Growth hormone inhibiting hormone (GHIH)=
somatostatin
Prolactin Inhibiting Hormone (PIH)=
Dopamine
Growth hormone is secreted by somatotrophs in the anterior pituitary. The releasing hormone (secreted by hypothalamus) would be ______ (GAS),while the inhibiting hormones would be _____ (BRAKES)
GHRH; GHIH
GH, a peptide hormone acts ____ on target tissues and as a ______ to the liver.
directly; tropic hormone
GH; a peptide hormones acts directly on target tissues and as a tropic hormone to the ____ which releases ____.
Liver; IGF-1
In what situation might growth hormone significantly increase and quickly?
prolonged starvation/fasting
Growth hormone acts tropically in the liver to activate ____, a cell signaling pathway that causes release of _____.
JAK-STAT; IGF-1
A cell signaling pathway in the liver activated by growth hormone that responds by release of IGF-1
JAK-STAT
What are some target tissues of growth hormone? (6)
- liver
- chondrocytes
- muscle cells
- adipose cells
- anterior pituitary (short loop negative feedback)
- hypothalamus (long loop negative feedback)
If GH acts on chondrocytes, what are some effects?
- increased amino acid uptake
- increased protein synthesis
GH acting on chondrocytes to increase amino acid uptake as well as protein synthesis is ultimately necessary for:
linear growth
In addition to GH acting on chondrocytes being necessary for linear growth, what is also necessary for linear growth?
IGF-1
GH can act on muscles to :
increase protein synthesis
In addition to growth hormone acting on muscles to increase protein synthesis what is also necessary for protein synthesis?
IGF-1
In excess, how does growth hormone affect adipose tissue?
anti-insulin action
What are two locations of negative feed back of the growth hormone?
- directly feeding back to anterior pituitary (short loop)
- feeding back to hypothalamus (long loop)
If negative feedback via growth hormone occurs on the hypothalamus, what hormone may be released?
Somatostatin
Describe the secretion of growth hormone:
pulsatile secretion; lower concentration during day with highest levels a few hours after sleep
When is the GH secreted at the highest levels?
a few hours after sleep
Growth hormone secretion can be stimulated by: (5)
- starvation (protein deficiency)
- fasting (hypoglycemia)
- acute stress
- exercise
- excitement
The secretion of GH during neonatal period:
The secretion of GH during childhood:
The secretion of GH during puberty:
The secretion of GH during adulthood:
- high secretion
- decreased secretion
- peak levels of secretion
- decreased secretion with age
Stimulation of GH release (5):
- GHRH
- Dopamine
- Catecholamines
- Excitatory amino acids
- Thyroid hormone
Inhibition of GH release (4):
- Somatostatin
- IGF-1 (due to negative feedback)
- High glucose levels
- FFA (High levels of free fatty acids)
Many of the growth and metabolic effects of GH are mainly produced by:
IGFs
IGFs can also be called:
somatomedins
IGF-1 is produced in most tissues and acts on neighboring cells in a _____ manner.
paracrine
The major site of IGF-1 synthesis:
liver
How many IGF binding proteins are there?
6
_____ in adults is one of the main growth promoting insulin-like growth factors
IGF-1
Osteocytes responding to mechanical sensors can release:
IGF-1
Osteocytes responding to ______ can release IGF-1
mechanical sensors
After osteocytes release IGF-1 what happens?
IGF-1 binds to receptors on osteoblasts to enhance bone formation
Mechanisms of action of GH and IGF-1:
Growth in nearly all tissues of the body, mainly IGF-1 occurs through what mechanisms?
- increased cell size
- mitosis
- differentiation of bone and muscle cells
Mechanisms of action of GH and IGF-1:
What is the overall outcome of the effects of GH and IGF-1 causing growth in nearly all tissues of the body?
- increased organ size
- increased organ function
- increased linear growth
Mechanisms of action of GH and IGF-1:
The effect of amino acid uptake protein synthesis in most cells results in:
increased lean body mass
Mechanisms of action of GH and IGF-1:
How does this effect glucose?
reduced glucose utilization
Mechanisms of action of GH and IGF-1:
Reduced glucose utilization is due to:
- decreased uptake
- increased hepatic glucose production
- increased insulin secretion
Mechanisms of action of GH and IGF-1:
The reduced glucose utilization can lead to:
insulin resistance ; diabetogenic
Mechanisms of action of GH and IGF-1:
Describe the effects on fatty acids:
mobilization of fatty acids from adipose tissue (lipolysis)
Mobilization of fatty acids from adipose tissues:
lipolysis
Mechanisms of action of GH and IGF-1:
Lipolysis results in:
increases FFA in blood and use of FFA for energy
Before fusion of the epiphyseal plates, GH and IGF-1 stimulate:
chondrogenesis and widening of the epiphyseal plates
Following GH and and IGF-1 stimulating chorndrogenesis and widening of the epiphyseal plates, what occurs?
Bone matrix deposition stimulating linear growth
In adults, GH and IGF-1 play a role in regulating the normal physiology of:
bone formation
In adult, how do GH and IGF-1 play a role in regulating the normal physiology of bone formation?
by increasing bone turnover
How do GH and IGF-1 stimulate the increase in bone turnover (there by regulating bone formation)
- activation of osteoblasts (MAINLY)
- increasing bone resorption via osteoclasts (lesser extent)
Kids: GH and IGF-1 =
Adults: GH and IGF-1=
chondrogenesis
increased bone turnover
Osteoblasts are of what origin?
mesenchymal precursers
What is responsible for the formation of active osteoblasts from the osteoblast precursor?
IGF-1
Gigantism occurs in _____; while acromegaly occurs in ____.
children; adults
Excess growth hormone in children leading to gigantism is typically caused by:
pituitary tumor (90%)
What areas are commonly involved with pituitary tumors that give rise to gigantism?
sella and cavernous sinus
Tumor causing excessive growth hormone release:
somatotropic adenoma of the pituitary
Describe the facial features associated with Gigantism/acromegaly: (4)
Coarse facial features, large fleshy nose, frontal bossing, jaw malocclusion
Coarse facial features, large fleshy nose, frontal bossing, and jaw malocclusion are collectively referred to as:
acromegalic faces
What issue with the thyroid may occur with gigantism/acromegaly
goiter
Describe the potential affects on the heart and what conditions may occur as a result due to gigantism/acromegaly:
cardiomegaly; hypertension and coronary heart disease
Describe the chest and spine in individuals affected by acromegaly/gigantism:
barrel chest and kyphosis and hyperostosis
The abnormal glucose tolerance and secondary insulin resistance in an acromegaly/gigantism individual may result in:
diabetes mellitus
Growth hormone shifts the body from utilizing ______ to _____ for metabolisms:
carbs to fats
Describe the reproductive consequences of gigantism/acromegaly:
male sexual dysfunction and menstrual disorders
Describe what can occur due to the thickened skin and hypertrophy of sebaceous and sweat glands in gigantism and acromegaly:
Hyperhidrosis and oily skin
Hyperhidrosis and oily skin in acromegaly/gigantism individuals can occur due to:
thickened skin (hypertrophy of sebaceous and sweat glands)
What can occur in the joints of individuals with gigantism/acromegaly
degenerative arthritis
Describe the neuronal effects caused by gigantism/acromegaly:
parathesias due to peripheral neuropathy
What is a potential treatment for pituitary microadenoma?
adenectomy via transphenoid approach followed by medications
Oral manifestations of GH excess: (7)
- thick rubbery skin, enlarged nose and thick lips
- macrocephaly
- macrognathia
- disproportionate mandibular growth
- anterior open bite and malocclusion
- macroglossia, dyspnea, dysphagia, dysphonia, sialorrhea,
- Hypertrophy of pharyngeal and laryngeal tissues
enlarged head =
enlarged jaw =
macrocephaly
macrognathia
The disproportionate mandibular growth caused by excess growth hormone includes:
mandibular prognathism- jaw jets forward
generalized diastemata- separation of teeth
The anterior open bite and malocclusion in caused by excess GH is due to:
combo of macrognathia and tooth migration
- Macroglossia:
- Dyspnea:
- Dysphagia:
- Dysphonia:
- Sialorrhea:
- enlarged tongue
- difficulty breathing
- difficulty swallowing
- difficulty speaking
- slobbering
The hypertrophy of the pharyngeal and laryngeal tissues in individuals with excess GH can cause_____ and how?
sleep apnea - because of the increased growth of the pharyngeal and laryngeal tissues obstructing the airway
What are the causes of growth hormone deficiency? (5)
- hypothalamic disorders
- mutations
- combined pituitary deficiencies
- radiation
- psychosocial deprivation
Combined pituitary hormone deficiencies=
panhypopituitarism
What type of mutations may lead to GH deficiency?
GHRH receptor, GH gene, GH receptor, IGF-1 receptor
A decrease in GHRH or an increase in GHIH could lead to:
growth hormone deficiency
What depends on the time of onset and severity of hormone deficiency? (talking about GH)
clinical manifestations
The clinical manifestations caused by complete growth hormone deficiency include: (4)
- slow linear growth rates (shorter stature)
- normal skeletal proportions
- pudgy, youthful appearance (decreased lipolysis)
- In setting of cortisol deficiency –> hypoglycemia
most common form of dwarfism, autosomal dominant condition, resulting from a mutation in the FGF-3 receptor in the cartilage and brain.
achondroplasia
The FGF-3 receptor mutation in achondroplasia makes the receptor overly active and it inhibits cartilage growth at growth plates so:
limb growth is reduced (growth of trunk is not is not impacted)
mutated receptor in achondroplasia:
FGF-3
Oral manifestations of GH deficiency include:
- disproportionate delayed growth of the ____ and ____ = ____ facial appearance
- ____ and ___ of the ___ regions of the jaws are abnormal and may be disproportionately smaller than adjacent anatomic structures.
- solitary ______.
- eruption of primary and secondary dentition and shedding of deciduous teeth are _____.
- skull and facial skeleton; small
- tooth formation and growth ; alveolar
- median maxillary central incisor
- delayed
How are the oral manifestations of GH deficiency managed?
correction of dental and skeletal malocclusion
Incisor defects in a child with growth hormone deficiency occurs in both:
primary and permanent dentition
In oral manifestation of GH deficiency:
The tooth formation and growth of the alveolar regions of the jaws are abnormal and may be disproprotionately smaller than adjacent anatomic structures, this can cause:
- tooth crowding and malocclusion
- plaque accumulation
- poor oral hygiene
- gingivitis and perio disease
The posterior pituitary contains ~100,000 ______ whose cell bodies are in the ____.
unmyelinated axons of neurons; hypothalamus
Areas of concentrated neuronal cell bodies in the hypothalamus that haev axons that go through the infundibulum with their synaptics terminals located in the posterior pituitary gland
paraventricular nucleus and supraoptic nucleus
The paraventricular nucleus produces:
oxytocin
The supraoptic nucleus produces:
ADH
List all the names for the abreviation ADH:
- Antidiuretic hormone
- Arginine Vasopressin (AVP)
Both ADH and Oxytocin are classified as:
neurohormones
Both ADH and Oxytocin are neurohormones made of:
polypeptides of nine amino acids
While the paraventricular nucleus secretes Oxytocin and the and the supraoptic nucleus secretes ADH, they both have the ability to:
secrete some of the other neurohormone
Describe the similarities between ADH and Oxytocin:
VERY Similar structure
What are the 2 primary functions of ADH:
- vasocronstriction (smooth muscle and blood vessels)
- antidiuretic (holds on to water)
ADH/AVP mechanism of action:
- Contaction of vascular smooth muscle via _____
V1 receptors
When ADH causes contraction of vascular smooth muscle through V1 receptors, what results:
increase in BP
V1 stands for:
Vasopressin 1 receptor
When ADH acts on V1 receptors, what occurs?
Contraction of vascular smooth muscle (blood vessels) (leading to increase in BP)
ADH/AVP mechanism of action:
ADH functions in the renal tubules via:
V2 receptors
Where are the V2 receptors (for ADH) located?
Late distal tubule and collecting duct
What results when ADH binds to V2 in the late distal tubule and collecting duct?
AQP2 proteins are inserted into the apical membrane of tubular epithelial cells
Where is APQ2 inserted following ADH binding to V2 receptors?
the apical membrane of tubular epithelial cells
Following ADH binding to V2 receptors in the renal tubule, and AQP2 being inserted into the apical membrane of tubular epithelial cells, what results?
This allows for water resabsorption (in accordance with AQP3 and AQP4) on the basolateral membrane)
For whater reabsorption to occur, through AQP2, what also has to be present?
AQP3 and AQP4 in the basolateral membrane
The V2 receptors in the late distal tubule and collecting duct and _____ receptors
GPCR
Although water can go through the apical membrane via simple diffusion, the aquaporins allow for:
water channels so a lot more reabsorption can occur
______ allows for water to enter the apical membrane, and _______ are always on the basolateral membrane and allow for the continuation of the water.
Aquaporin 2; Aquaporin 3&4
Stimuli for ADH secretion:
- Decreased blood volume
- Increased osmolarity
- Decreased BP
In regard to ADH secretion, decreased blood volume is considered:
Isotonic
In regard to ADH secretion, increased osmolarity is considered:
Isovolemic
The most potent stimulator for ADH release is:
increased osmolarity (linear on a graph)
If blood volume goes down, ADH will function to _____ to resolve the issue.
Keep water
If the osmolarity of plasma is too high, ADH will function to _____ in order to _____.
keep water; dilute it
If your BP is too low, ADH will function to _______ in order to raise it.
keep water
ADH working to keep water in the body will resolve what 3 issues?
- high osmolarity
- low BP
- decreased blood volume
Decreased or absent feeling of thirst
hypodipsia
Hypodipsia may result in ______; which can cause ____.
reduced intake of water; hypernatremia
A common problem in elderly but is also associated with lesions in the hypothalamus (thirst center), head trauma, occult hydrocephalus or subsrachnoid hemmorhage
hypodipsia
List causes of hypodipsia: (5)
- eldery people
- lesions in hypothalamus (thirst center)
- head trauma
- occult hydrocephalus
- subarachnoid hemorrhage
Diabetes insipidus is caused by:
ADH inbalance
What are the two types of DI?
neurogenic (central)
nephrogenic (peripheral)
What do DI and DM have in common?
Large urine output
If you have an increased osmolarity, your would feel:
thirsty (under normal conditions)
Disease caused by inability to produce and secrete ADH:
Neurogenic/central diabetes insipidus
Describe the ADH levels in an individual with neurogenic/central DI:
Low levels of ADH (they are unable to produce/secrete it)
Treatment for a patient with neurogenic/central DI would be:
To supplement the ADH (give them ADH)
A person with a tumor near the posterior pituitary gland has surgical removal of the tumor causing damage to the supraoptic nucleus in the posterior pituitary.
What might this result in if they are unable to produce ADH.
Neurogenic/central DI
Lacking a response to ADH (like a resistance):
Nephrogenic/peripheral DI
Nephrogenic/peripheral DI occurs in the:
kidneys
When ADH is present but the kidneys either do not respond at all or respond inappropriotely:
Nephrogenic/peripheral DI
Describe the levels of ADH in someone with nephrogenic/peripheral DI; why?
High levels, because they can produce ADH and the stimulus causing the ADH secretion does NOT get corrected (causing the hypothalamus to secrete more and more)
Uncharacteristically really high levels of ADH secretion and not because it is needed (oversecretion of ADH)
Syndrome of innappropriate ADH (SIADH)
A patient with DI may present with:
polyuria
Excretion of large volumes of urine:
polyuria
Describe the urine in a patient with DI:
hypotonic and tasteless (Insipid)
Other causes of polyuria may include: (Not DI)
- primary ingestion of excess fluid
- Increased metabolism of ADH (pregnancy)
Primary ingestion of excess fluid:
primary polydipsia
Increased and uncontrolled secretion of ADH that causes volume expansion and hyponatremia:
Syndrome of inappropriate ADH (SIADH)
In the case of a patient with SIADH, what would the increased secretion of ADH cause? (2)
- volume expansion
- hyponatremia
Relative to a dentist, what can cause excessive ADH release?
surgery, pain and stress
Why do pregnant women pee more?
during pregnancy, ADH metabolism (breakdown of ADH) is increased, so more water is released
What hormone causes milk ejection from the breasts in lactation?
Oxytocin
What hormone stimulates contraction of the uterus toward the end of gestation?
oxytocin
Where is oxytocin released from?
posterior pituitary
Describe the feedback of oxytocin release:
positive feedback
Describe the relationship between oxytocin and prolactin:
permissive
Where is prolactin released from?
anterior pituitary
What does prolactin cause?
milk production
What causes the milk ejection in the breast? (mechanism)
myoepithelial cell contraction
What causes uterine contraction? (mechanism)
stretch of cervix at end of pregnancy
Objective evidence of a disease that can be seen or measured:
sign
Enlarged hands, polyuria, and tachycardia are all examples of:
signs
Cannot be measured (they are subjective) but are reported by the person:
symptoms
Headache and numbness are both examples of:
a symptom
Plasma Membrane Hormone Receptors:
List the 4 plasma membrane hormone receptors:
- G-protein coupled
- Tyrosin Kinase
- Serine kinase
- Cytokine
Plasma Membrane Hormone Receptors:
What are our two types of G-protein coupled receptors?
Gs and Gq
Plasma Membrane Hormone Receptors:
Elaborate on the type of Gs coupled receptors:
What second messenger(s) do they produce?
- B-adrenergic
- Calcitonin
- ACTH
- Glucagon
- TSH
- Vasopressin
The produce the second messenger cAMP
Plasma Membrane Hormone Receptors:
Elaborate on the types of Gq coupled receptors:
What second messenger(s) do they produce?
- A-adrenergic
- Angiotensin II
- TRH
They produce the second messengers IP3, DAG and Ca2+
What type of plasma membrane hormone receptor would insulin and IGF-1 bind to?
Tyrosine kinase
What type of plasma membrane hormone receptor would growth factor bind to?
Tyrosine kinase
After cytokine binds to its plasma membrane hormone receptor (leptin), what second messenger does it activate?
JAK-STAT
Why would some receptors such as the receptors for insulin and thyroid hormone be more widely distributed?
Because the effects of these hormones is something we want a lot of cells to respond too
About 93% of the active hormones secreted by the thyroid gland is:
T4
About 7 % of the active hormones secreted by the thyroid gland is:
T3
T4=
T3=
Thyroxine
Triiodothyronine
What thyroid hormone is more potent?
T3
Thyroid hormones impact ____ & _____ and also have a _____ action on ______.
metabolism & growth/development; permissive; catecholamines
What thyroid cells are involved in making thyroid hormone?
T-Thyrocyte cells
What is stored in the colloid of the follicle?
Thyroglobuline
Parafollicular cells secrete:
calcitonin
What is the action of calcitonin?
Tone down plasma calcium (decrease)
In the middle of the thryoid follicle=
colloid
Where is thyroid hormone made and stored until it is time to be released?
colloid
What is required for thyroid hormone synthesis?
Iodine (I2)
Thyroid hormone requires Iodine because this is needed for:
thyroid follicular cells to actively transport iodide (I-) obtained from the diet
Iodine synthesis steps
- Thyroid hormone synthesis requires ____
- _____ comes from the diet
- Thyroid follicular cells contain a transporter called:
- The follicular cells will:
- The iodide gets into the cell and a second transporter called ____ removes ____ and brings ____ into the colloid
- Once inside the colloid, the Iodide gets converted into ____.
- Iodine
- Iodide
- Na+/I- symporter (NIS)
- Concentrate the Iodide
- Pendrin; chloride; iodide
- Iodine
The Na+/I- transporter is a:
symporter
The Na+/I- symporter is a ______ transporter
secondary active
Iodide must exit the____ across the ____ to access the ___ where the initial steps of thyroid hormone synthesis occur.
thyrocyte; apical membrane; colloid
What enzymes works in the iodination and coupling process?
Peroxidase
What is a general term we give for anion exchangers?
pendrin
Pendrin is a ___ that exchanges ___ for ____ bringing _____In and _____ out in the process of thyroid hormone synthesis
anion exchanger; Cl-/I-
I- in and Cl- out
Pendrin is ALWAYS:
moving two negatively charged substances in opposite directions
T3 and T4 are produced in the colloid and complexed with:
Thyroglobulin
The enzyme involved in all of the production steps in the formation of thyroid hormone (tyrosine, monoiodotyrosine, diiodotyrosine, T3, RT3, and T4)
peroxidase
Thyroglobulin is made of:
a bunch of tyrosine amino acids
Which works first in making T3 and T4 (pendrin or peroxidase???)
pendrin THEN peroxidase
T3 and T4 secretion into the blood:
- _____ is internalized by endocytosis
- The vesicles fuse with ____ in the cell
- _____ cleaves T3 and T4 from ____.
- T3 and T4 diffuse out of the cell and into ____.
- colloid
- lysosomes
- protease; TG
- capillaries
Colloid is a _____ of thyroid hormones
reservoir
Majority if not all of T3 and T4 bind with _____ for transport
plasma proteins
What are the plasma proteins that T3 and T4 bind to?
Thyroxine binding globulin (TBG)
Transthryretin (TTR)
Albumin
What causes the long half life of T4?
strength of its binding to the transport protein
Because T3 doesn’t bind as tightly to the transport protein, its half life is:
2-3 days
T3 and T4 secretion into the blood:
Colloid is taken into the follicular cell via:
pinocytosis
T3 and T4 secretion into the blood:
T3 and T4 undergo _____ to be secreted into the blood
simple diffusion
Target cells make active T3 by using enzymes called ______ that remove an iodine from T4.
deiodinases/iodinases
Individual target cells can alter their exposure to T3 by regulating:
their tissue deiodinase synthesis
What are the 3 different deoiodinases?
D1, D2, D3
All three of the deiodinases contain a rare amino acid called:
selenocysteine
In selenocysteine, there is a ______ molecule in the place of ____ which is essential for the enzymatic activity.
selenium; sulfur
What are carious conditions that inhibit deiodinase activity?
- selenium deficiency
- burns
- trauma
- advanced cancer
- cirrhosis
- chronic kidney disease
- MI
- febrile states
- fasting
- stress
If someone has a condition that inhibits deiodinase activity, they could show signs of:
Why?
hypothyroidism (because they are not able to convert T4 to T3)
T3 action occurs ____ compared to T4
sooner
When does the maximum activity of T3 hormone occur?
~2-3 days
Compare the activity of T4 to T3
T4 has a slower onset but long duration of action (can last until about 40 days)
A variety of genes have the thyroid hormone response element which can lead to:
gene transcription and synthesis of new proteins
The synthesis of new proteins due to the action of T3 and T4 can lead to what 5 main responses?
- metabolism
- Cardiovascular response
- CNS development
- Growth
- Many other system responses
A big effect of the thyroid hormone is on metabolism, what effects can be seen due to T3 and T4 synthesizing new proteins that affect metabolism?
- Increased BMR
- Increased Glucose absorption
- Increased gluconeogenesis
- Increased glycogenolysis
- Increased lipolysis
- Increased protein synthesis
- Increased O2 consumption
- Increased mitochondria
- Increased Na+/K+ ATPase activity
Background amount of oxygen utilized by cells; a basic indicator of metabolism:
BMR
A big effect of the thyroid hormone is on the cardiovascular system. What are some effects relating to this?
- Increased cardiac output
- Increased tissue blood flow
- Increased HR
- Increased heart strength
- Increased respiration
The cardiovascular effects of thyroid hormone are caused by an increased in ______ which is a _____ effect.
beta receptors; permissive effect
Negative feedback of the thyroid hormone is mainly at the level of ____ but can also occur at ____.
anterior pituitary; hypothalamus
It is T4 that is the circulating form of thyroid hormone that is able to cause the feedback inhibition, but it gets converted into T3 in the _____ and ____, so its actually the T3 that inhibits the secretion of _____ and _____.
anterior pituitary and hypothalamus
TSH and TRH
What actually causes the feedback inhibition of thyroid hormone?
The anterior pituitary and hypothalamus increasing their expression of deiodinase activity so when T4 levels in these tissues increase, they readily convert it (via deiodinase) to T3 which causes the inhibition
Describe the secretion of TSH:
pulsatile with increases in evening hours and peak ~ midnight
Describe the secretion of Thyroid hormone:
Thyroid secretion mirrors TSH secretion (pulsatile with increases in evening hours and peak around midnight) but also is tonically secreted (small amounts)
Thyroid hormones stimulates _____ by most metabolically active tissues
oxygen consumption
How does thyroid hormone effect BMR?
increases it
Thyroid hormone stimulates ______ metabolism
carbohydrate
Thyroid hormone stimulates carbohydrate metabolism by:
- uptake of glucose by cells
- enhances glycolysis and gluconeogensis
- increases CHO absorption from GI tract
Describe the effects of thyroid hormone on metabolism relating to proteins:
stimulates protein catabolism and synthesis but more catabolism (breakdown)
Describe the effects of thyroid hormone relating to fat:
stimulates fat metabolism
Thyroid hormone stimulates fat metabolism by:
`
increasing lipid mobilization and oxidation of fatty acids
Thyroid hormone is required to convert _____ to ___ which is why hypothyroid patients may exhibit yellow skin
beta carotene —> vitamin A
Vitamin A is important in:
wound healing
Thyroid hormone is responsible for decreasing circulating _____ levels.
A person with hypothyroid may have _____ due to this.
cholesterol levels
hyperlipidemia
With no thyroid hormone at all, what would the BMR look like?
BMR levels would be around 45-50% of normal rate
Thyroid hormone is needed for ______ regarding the nervous system.
needed for normal devleopment
Thyroid hormone impacts _____ so someone with hypothyroidism may have prolonged ___.
reflex time; prolonged reflex time
In someone with hyperthyroidism, due to the increased neuronal synapses they may experience:
muscle tremors
If someone feels tires, but has difficulty sleeping and anxiety, worry and paranoia they may have: (relating to thyroid hormone)
hyperthyroidism
hyperthyroidism effected on cardiovascular system include:
- increased expression of B-adrenergic receptors
- increased blood flow, HR, and heart contractility
Describe the permissive effect of the thyroid hormone on the cardiovascular system. What might this cause?
Thyroid hormone increases the expression of beta adrenergic receptors, and this would lead to an increased SNS response
Thyroid hormone effects on the endocrine system:
Increased ____ consumption that results in increased _____ secretion needed to maintain ____ levels.
glucose; insulin; blood glucose
Thyroid hormone effects on the endocrine system:
The thyroid hormone causes activation of bone formation so this causes a need for increased:
PTH secretion
Thyroid hormone effects on the endocrine system:
Causes increased inactivation of ______ which leads to more _____ release by the ____.
glucocorticoids; ACTH; anterior pituitary
Thyroid hormone effects on the GI system:
Thyroid hormone causes increased _____ and _____ intake.
appetite and food
Thyroid hormone effects on the GI system:
Thyroid hormone causes increased rate of ______ and _____ of GI tract.
Individuals with hyperthyroidism may have _____ due to this, while individuals with hypothyroidism may have ____ due to this.
secretion and motility
diarrhea; constipation
Enlarged thyroid gland=
goiter
Goiter is an enlarged thyroid gland that:
DOES NOT indicate functional status
Goiter can be seen in:
hypothyroidism, hyperthyroidism and euthyroidism
Goiter can be caused excessive amounts of _____ secretion.
TSH
High TSH stimulates thyroid to stimulate larges amounts of _____ into ______ resulting in gland enlargement/ goiter
Thyroglobin colloid into follicles
The most common form of hyperthyroidism
Grave’s disease
Although Grave’s disease is the most common form of hyperthyroidism, hypothyroidism can also occur due to:
thyroid adenoma
Grave’s disease is a _____ disease.
Explain this:
autoimmune disease.
Antibodies to the TSH receptor called thyroid stimulating immunoglobulins are produced, and they stimulate the thyroid gland DIRECTLY to produce too much thyroid hormone (T3 and T4)
Describe the category of disorder that Grave’s disease is, and who the hypothalamus and anterior pituitary are affected:
Primary endocrine disorder- bc issue is at level of thyroid gland
strong negative feedback causes TSH and TRH levels to be reduced
Grave’s disease is more common in:
The gals
List the signs and symptoms of Grave’s dizzzeeeez
- sweating/heat intolerance
- increased metabolism
- increased appetite
- weight loss
- fine hair/ protein synthesis
- increase NS response (emo instability, insomnia, nervy, resletessness)
7.fine tremor - goiter
- exophthalmos (bug eyed)
- pre-tibial myxedema
Treatment for the gravy:
radioactive iodine to ablate the thyroid followed by L thyroxine (T4) to prevent hypothyroidism, surgery rarely indicated
antithyroid drugs
beta-blockers to block permissive effect of thyroid hormone
Oral symptoms of hyperthyroidism may include:
- burning mouth syndrome
- gum disease
- excessive salivation
- weakening of mandible
- increased caries risk
Elevated thyroid hormone with stressful events or serious illness causing fever, tachycardia, elevated BP, nausea, vomiting, diarrhea and breathing problems:
thyroid storm (thyrotoxicosis)
What can bring on a thyroid storm?
-trauma
-surgery
-infection
-DKA
-MI
Overall a thyroid storm can be described as:
exaggerated sympathetic response
In patients with hyperthyroidism or those that exhibit signs/symptoms of it what is extremely important?
administration of epinephrine is CONTRAINDICATED and elective dental care should be deferred
autoimmune reaction against the thyroid gland that destroys it rather than stimulates it
hashimotos thyroiditis
What is the most common cause of hypthyroidism?
Hashimoto’s thyroiditis
Prior to diagnosis of hashimoto’s thyroiditis, most patients first exhibit:
autoimmine thyroiditis
In hashimoto’s thyroiditis, inflammation leads to ___ of the thyroid resulting in _____.
fibrosis; decreased section of thyroid hormone
What is the target of the antibodies in hashimotos thryoiditis?
peroxidase
What class of disorder is Hashimoto’s characterized by?
primary endocrine disorder
Another form of hypothyroidism (not hashimoto’s) is due to:
low iodine
Hypothyroidism due to low iodine is classified as:
primary endocrine disorder
In the absence of iodine, describe the levels of T3 and T4, TRH and TSH:
T3 and T4 low; and TRH and TSH high
In hypothyroid states, goiter is due to _____, while no goiter is due to _____.
iodine deficiency; TSH deficiency
Hypothyroidism due to iodine deficiency = ______ = _____ deficiency
Hypothyroidism due to TSH deficiency = _______ = ______ deficiency
goiter; primary
no goiter; secondary
Symptoms of hypothyroidism may include:
- weight gain
- constipation
- cold/diminished perspiration
- lethargy
- impaired memory
- lack of NS stimulation
- coarse, dry, brittle hair
- hair loss
- loss of lateral eyebrows
- slow pulse (bc decreased # of beta receptors)
- enlarged heart
- facial edema
- peripheral edema
Unique symptom seen in severe hypothyroid cases:
myxedema
In hyperthyroidism patients, where does the myxedema occur?
In hypothyroidism patients, where does the myxedema occur?
hyper= pretibial myxedema
hypo= face
Myxedema occurs due to increased quantities of ____ and ____ bound with protein plus water that accumulates in the skin
hyaluronic acid and chondroitin sulfate
Dull expressionless facies with puffiness of eyelids, swollen, cool, waxy, dry, coarse, and pale skin with lots of creases describes a patient effected with ______ and the treatment would be ______.
myxedema; L-thyroxine (T4)
Required for post-natal brain maturation
Thyroid hormones
Results from congenital absence of thyroid gland:
congenital cretinism
Results from iodine deficient diet; most common cause world wide:
endemic cretinism
Cretinism can cause ______ of neonates.
Skeletal growth is more inhibited than soft tissue growth resulting in:
physical and mental retardation
Obese, stocky and short with large protruding tongue
Cretinism can cause lack of development of ____.
nervous system
List the hypothyroidism oral manifestations: (6)
- macroglossia
- dysgeusia
- delayed tooth eruption
- poor wound healing
- increased periodontal disease
- salivary gland enlargement
The poor wound healing and increased risk of infection in a hypothyroidism patient is due to:
decreased activity of fibroblasts
Patients with hypothyroidism are sensitive to:
central nervous system depressants and barbiturates
85% of the body’s phosphate is stored in the:
14-15% of the body’s phosphate is stored in the:
Less than 1% of the body’s phosphate is stored in the:
bones
cells
ECF
Only 0.1% of the body’s calcium is found in the:
1% of the body’s calcium is found in the:
The rest of the body’s calcium is stored in the:
ECF
Cells and organelles
bones
When levels of calcium are too low:
neuronal hyper-excitability (tetany due to extra Na+ influx)
When levels of calcium are too high:
neuronal depression (blocks Na+ influx)
Carpal spasms can be due to:
HYPOcalcemia
Control points for calcium and phosphate include:
- absorption- via intestines
- excretion- via urine (calcium and phosphate) and feces (calcium only)
- temporary storage- via bones (hydroxyapatite)
Ca(10)PO4(6)OH(2)
hydroxyapatite
What the hormones that regulate plasma calcium?
PTH, Calcitriol, and Calcitonin
How does PTH regulate plasma calcium and phosphate?
Increases plasma calcium
Decreases plasma phosphate
How does PTH work to raise plasma calcium and lower plasma phosphate?
- mobilizes calcium from bone
- Enhances renal reabsorption of calcium
- Increases intestinal absorption of calcium (INDIRECTLY)
How does calcitriol regulate plasma calcium and phosphate?
Increases plasma calcium
Increases plasma phosphate
How does calcitriol work to raise plasma calcium and phosphate?
Calcitriol is the primary hormones that enhances intestinal absorption of calcium and it also causes absorption of phosphate
The primary hormone that enhances intestinal absorption of calcium and also causes absorption of phosphate.
Calcitriol
What are the other names for calcitriol?
1,25-dihydroxycholecalciferol
Vitamin D3
Calcitriol acts on the intestines ______ to enhance absorption of calcium and also phosphate. While PTH acts on the intestines _____ to enhance absorption.
Directly; Indirecty
Calcitonin comes from:
parafollicular cells of the thyroid gland
How does calcitonin regulate plasma calcium and phosphate?
Decreases plasma calcium and phosphate
How does calcitonin work to lower plasma calcium and phosphate?
It stimulates bone formation
What hormones stimulate bone formation?
- calcitonin
- insulin
- growth hormone
- IGF-1
- estrogen
- testosterone
______ & _____ stimulate bone matrix resorption which functions to increase plasma calcium
Calcitriol and PTH
Calcitriol and parathryoid hormone stimulate bone matrix _______ .
How does this effect plasma calcium?
resorption; increases plasma calcium
Bone resorption:
- Osteoblasts release ______.
- ____ binds to the _____ on preosteoclasts and this leads to activation of _____.
1.RANK ligand
2. RANK-L binds to the RANK receptors; osteoclasts
What is the goal of bone resorption?
Increase plasma calcium levels
What type of cell is activated during bone resorption? What activates this type of cell?
Osteoclasts; Rank Ligand
Factors that stimulate bone matrix resoprtion:
- PTH
- Excessive levels of calcitriol
- Prolactin
- Corticosteroids
What is the goal of bone deposition?
form bone, take calcium out of blood and put into bone
_____ stimulates bone matrix deposition and inhibits osteoclasts.
calcitonin
Calcitonin stimulates bone matrix deposition and inhibits osteoclasts which ultimate does _____ to plasma calcium.
decreases
If calcium levels in the blood are sufficient, we don’t need to:
break down bone
Anabolic or anti-resorptive factors (for bone)=
- estrogens
- calcitonin
- testosterone
- calcium
- BMP
In order to avoid RANK-L further activating osteoclasts, ____ will bind to RANK-L to prevent it from binding to the RANK-L receptor
OPG
OPG binding to RANK-L ultimately leads to:
apoptotic osteoclasts
Osteoclasts that do NOT function to break down bone:
Apoptotic osteoclasts
Affects almost 10 million individuals in the US, though only a small proportion are diagnosed and treated. Occurs when there is an imbalance between bone formation and resorption.
Osteoporosis
Risk factors for osteoporosis: (Superficial)
- Vitamin D deficiency
- Inadequate calcium intake
- Glucocorticoid medications
- Reduced physical activity
- Estrogen deficiency
- Cigarette smoking
- Alcohol
Describe why Vitamin D deficiency can lead to osteoporosis:
Because it can lead to really high PTH levels (secondary hyperparathyroidism) which leads to excessive bone breakdown
Describe why inadequate calcium intake can lead to osteoporosis:
Because it can lead to really high PTH levels (secondary hyperparathyroidism) which leads to excessive bone breakdown
Describe why glucocorticoid medications can lead to osteoporosis:
They supress the immune response leading to risk of weak and brittle bones
Describe why post-menopausal estrogen deficiency can lead to osteoporosis:
Estrogen stimulates the process of bone matrix deposition, so lack of estrogen would throw the balance off
Treatments for osteoporosis include:
- exercise
- PT
- Estrogen replacement
- Calcium
- Vitamin D
- Bisphosphonates
When giving vitamin D to an osteoporosis patient, you must make sure _____ levels do not get too high
PTH
Four pea-sized glands on the posterior surface of the thyroid gland:
Parathyroid glands
Parathyroid hormone (PTH) is secreted by:
chief cells
What are the effect of PTH? How?
Increased plasma calcium by indirectly increasing intestinal absorption, decreasing renal excretion and increasing bone resorption
How does PTH decrease plasma phosphate?
Increasing renal excretion
Describe the renal excretion effects on calcium and phosphate by PTH:
Increases renal excretion for phosphate
Decreases renal excretion for calcium
Why is the effect of PTH on intestinal absorption of calcium considered indirect?
It causes more synthesis of vitamin D, which in turn causes more intestinal absorption of calcium.
When PTH is secreted to to decreased ECF calcium, this leads to:
Hypertrophy of parathyroid gland
How would a decrease in ECF calcium concentration effect the rate of PTH secretion:
Increase
What conditions would lead to hypertrophy of the parathyroid gland:
Chronic cases - pregnancy, rickets, and lactation
Chronically, if you hypertrophy the parathyroid gland, it becomes:
even better at secreting PTH
Increased ECF concentration of calcium leads to ______ of the parathyroid gland.
decreased activity
If the parathyroid gland has a decrease in activity, it will have a ____ in size.
decrease
What conditions can cause a decrease in activity and size of the parathyroid gland?
- increased Vitamin D intake at excessive levels
- Excess quantities of calcium in diet
- bone resorption caused by factors other than PTH
Describe the effect on plasma calcium:
Bone resorption:
increases plasma calcium
Describe the effect on plasma calcium:
Resabsorption of calcium by renal tubules
increases plasma calcium
Describe the effect on plasma calcium:
Conversion of 25-hydroxycholecalciferol to 1-25dihydroxycholecalciferol
increases plasma calcium
Describe the effect on plasma phosphate:
Decreased reabsorption by renal tubules:
decreases plasma phosphate
Where do we get cholecalciferol (vitamin D3) from:
skin (from sun)
In the process of calcitriol synthesis, cholecalciferol is converted to ______ ; by what organ?
25-hydroxycholecalciferol ; liver
In the process of calcitriol synthesis, 25-hydroxycholecalciferol is converted to _____; by what organ?
1-25 dihydroxycholecalciferol (Calcitriol); kidney
What tells the kidney to do the conversion of 25-hydroxycholecalciferol to the active form?
parathyroid hormone
Where is the main effect of calcitriol?
Intestines - absorption of calcium and phosphate from diet
Where can calciferol act although not the main effect?
Kidneys (reduced excretion of calcium and phosphate); Bones (indirectly causes bone deposition)
Vitamin D3 can be stored in the liver for:
several months
Describe the regulation of calcitriol levels:
tightly regulated- if someone takes excess vitamin D3 the liver will still only convert so muc into the 25-hydroxycholecalciferol
Someone with a compromised liver or kidney function may exhibit:
Vitamin D deficiency
peptide hormone secreted by parafollicular cells
calcitonin
Parafollicular cells reside in the _____ and may also be called _____.
thryoid gland; C-cells
Calcitonin is released in response to:
elevated free plasma calcium
Calcitonin lowers the level of plasma calcium by decreasing the activity of ____, thus decreasing _____.
decreases the activity of osteoclasts thus decreasing bone resorption
Not a major controller of calcium in humans:
calcitonin
What two systems does calcitonin act on?
bone and kidneys
Excess PTH secretion due to a parathryroid gland tumor:
primary hyperparathyroidism
Primary hyperparathyroidism can lead to extreme _____ activity in bones causing _____, more specifically ____.
osteoclastic activity; cystic bone disease; osteitis fibrosa cystica
Such excessive bone breakdown that we we see scar tissue and fibrosis in bones
cystic bone disease (osteoitis fibrosa cystica)- primary hyperparathryoidism
Primary parathyroidism can cause hypercalcemia leading to: (in relation to urine)
polyuria and calciuria
What happens to phosphate levels and why in patients with primary hyperparathyroidism:
low phosphate due to increased renal excretion
Describe why someone with primary hyperparathyroidism would exhibit muscle weakness and easy fatigability:
too much calcium blocks sodium influx leading to neuronal depression (impedes signaling by neurons)
Primary hyperparathyroidism signs and symptoms include:
Stones, Bones, abdominal groans, and psychic moans
Describe the stone component to primary hyperparathyroidism:
- renal stones
- nephrocalcinosis
- polyuria
- polydipsia
- uremia
Describe the bones component to primary hyperparathyroidism:
- cystic bone disease
- osteomalacia/rickets
- arthritis
Describe the abdominal groans component of primary hyperparathyroidism:
- constipation
- indigestions
- nausea
- vomiting
- peptic ulcers
- pancreatitis
Describe the psychic moans component of primary hyperparathyroidism:
- lethargy/fatigue
- depression
- memory loss
- paranoia
- personality change
- confusion, suport, coma
Other symptoms not included in stones, bones, moans, and groans from primary hyperparathyroidism include:
- proximal muscle weakness
- Keratitis
- conjunctivitis
- Hypertension
- itching
High PTH levels that occur as compensation for hypocalcemia and not due to an issue with the parathyroid gland:
secondary hyperparathyroidism
What are the two causes of hypocalcemia that lead to secondary hyperparathyroidism:
- vitamin D deficiency
- chronic renal disease- cannot synthesize Vit D3
What disease are you at risk for with hight levels of PTH?
osteoporosis
Disease that would result from accidental surgical parathyroid gland removal, not common
primary hypoparathyroidism
What increases membrane Na+ permeability leading to neuromuscular excitability and muscle spasms
hypocalcemia
What the condition name for the wonky ass hand:
carpal spasm
How many adrenal glands and where are they located?
2 adrenal glands, located on top of each kidney
describe the structure of a adrenal gland?
outer cortex + inner medulla
What portion of the adrenal gland is essential for life?
Adrenal cortex
The adrenal cortex secretes:
- corticosteroids
- mineralcorticoids
- sex hormones
Is the adrenal medulla essential for life?
no
The adrenal _____ is a true endocrine organ
cortex
Although it is not essential for life, the adrenal medulla is important in:
Secreting epinephrine and norepinephrine in resonse to sympathetic nervous system stimulation
The adrenal medullary hormones are NOT essential for life, but help an individual deal with:
emergencies
The adrenal cortex secretes several hormones that are made from:
cholesterol
What are the 3 layers of the adrenal cortex?
Zona glomerulosa
Zona fasiculata
Zona reticularis
The largest zone of the adrenal cortex
fasculata
The zona glomerulosa secretes ______ and is regulated by ______.
mineralcorticoids; RAAS
RAAS stands for:
Renin-angiotensin-aldosterone system
The zona fasciulata secretes _____ and is regulated by _____.
glucocorticoids; HPA (CRH and ACTH)
HPA stands for:
hypothalamic-pituitary -adrenal axis
The zona reticularis secretes ____ and is regulated by ____.
androgens; HPA
The adrenal medulla is related to the ____ and secretes _____.
Sympathetic Nervous System; Catecholamines
What type of cells secrete catecholamines?
chromaffin cells
Where do the chromaffin cells of the adrenal medulla secrete Epi and NE?
into the blood
What are the three tissues involved in the HPA?
Hypothalamus, Pituitary, Adrenal gland
Why does the zona glomerulosa secrete so much aldosterone?
Because enzymes involve din the formation of aldosterone from cholesterol are highly expressed in the zona glomerulosa
What enzyme is responsible for the conversion of Cortisol to corisone?
11HSD Beta 2
What enzyme is responsible for the conversion of cortisone to cortisol?
11HSD Beta 1
The reactions that occur for the synthesis of steroid hormones in the adrenal cortex take place in the:
mitochondria or endoplasmic reticulum
Describe the activity of cortisone at cortisol receptors
reduced activity
Can be used to make testosterone and androgens:
Androstenedione
Aldosterone is classified as a:
mineralcorticoid
Aldosterone functions in the kidneys to:
- increased renal reabsorption of Na+
- increase renal secretion of K+
Aldosterone working to increase renal reabsorption of Na+ and increasing renal secretion of K+ results in:
Increase in ECF fluid volume and mean arterial pressure
What stimulates aldosterone secretion?
- angiotensin II
- Increased levels of K+
- Decreased levels of Na+
Aldosterone has effects on:
- kidney
- sweat glands
- salivary glands
What portion of the adrenal cortex is responsible for aldosterone secretion:
Zona glomerulosa
What are the main functions of angiotensin II?
- vasoconstriction
- release of aldosterone
What function of angiotensin II is interrelated to the sympathetic nervous system?
release of aldosterone
Since aldosterone causes increased tubular reabsorption of sodium, ultimately raising blood sodium levels, what happens water?
Water retention occurs because where sodium goes water follows
The effects of aldosterone on sweat glands is important to:
conserve body salt in hot environments
The effects of aldosterone on the salivary gland is important in:
conservation of sodium during high rates of salivary secretion
In addition to hyperkalemia, _____ causes secretion of aldosterone
angiotensin II
Enzyme released by the cells in the kidneys in response to a variety of stimui (example SNS)
Renin
Angiotensin converting enzyme (ACE) is produced by the:
endothelium
List the steps of RAAS
Angiotensinogen gets converted to angiotensin I by the enzyme Renin
Angiotensin I gets converted to Angiotensin II by the enzyme ACE
Angiotensin II ultimately causes secretion of _____ but also does _____, _____, and _____.
ultimately aldosterone secretion but also ADH secretion, thirst stimulation, and vasoconstriction
What do vasconstriction, aldosterone secretion, ADH secretion and thirst stimulation all have in common?
All these work to raise BP
In RAAS, the non-active precursor made by the liver and found in the plasma:
angiotensinogen
Where is large amounts of ACE found?
In the lungs- COVA
A lot of _____ medications target RAAS
HTN
How do ACE inhibitors work?
If you inhibit ACE you will make less angiotensin II
Primary hyperaldosteronism may also be called:
Conn’s Syndrome
In primary hyperaldosteronism, where is the problem?
adrenal gland
What are the causes of primary hyperaldosteronism?
- adrenal adenoma (benign)
- adrenal hyperplasia
- adrenal carcinoma (malignant)
Describe the levels of renin involved in primary hyperaldosteronism (Conn’s syndrome):
Low levels of renin
Signs and symptoms of primary hyperaldosteronism (Conn’s) include:
- HTN
- Hypernatremia
- Hypokalemia
- Headaches
- Weakness
- Fatigue
- HYPOKALEMIC ALKALOSIS
- LOW PLASMA RENIN
Explain why someone with primary hyperaldosteronism would have low levels of plasma renin:
Due to so much aldosterone being produced and it strongly negatively feedingback
A byproduct of cells trying to regulate the K+ levels in the case of primary hyperaldosteronism (Conn’s):
Hypokalemic alkalosis
In hypokalemic alkalosis, the cells attempt to regulate K+ levels and leads to an absence of:
H+ levels in the ECF
Treatment options for primary hyperaldosteronism (Conn’s) include:
surgical removal of tumor or most of the adrenal tissue when hyperplasia is present, or a minercorticoid receptor antagonist
Caused by decreased bloodflow and pressure in the renal artery, (the kidney thinks BP is low and secretes renin excessively)
Secondary hyperaldosteronism
Describe the levels of renin in secondary hyperaldosteronism:
High levels of renin
What are causes of secondary hyperaldosteronism?
- CHF
- Renal artery stenosis
How might CHF lead to secondary hyperaldosteronism?
Pumping function of the heart is declined leading to low BP, and aldosterone levels will rise to compensate
How might renal artery stenosis lead to secondary hyperaldosteroneism?
Renal artery pumps blood to kidney and there can be an atherosclerotic plaque in the vessel resulting in decreased bloodflow to kidney. The kidney now thinks BP is low and secretes excessive renin to try and compensate for the “low BP” and then that extra renin causes extra angiotensin II which leads to extra aldosterone
The other kidney is working just fine
Signs and symptoms of secondary aldosteronism include:
- high plasma renin
- hypernatremia with extracellular volume expansion
- edema
- decreased cardiac output
- similar clinical findings as primary hyperaldosteronism
Hormone that functions in the mobilization of energy stores and suppresses the immune system:
Cortisol
What hormone is secreted in response to stress?
Cortisol
Cortisol is categorized as a _____ and comes from the _____ zone of the adrenal cortex
glucocorticoid; zona fasiculata
More cells in the adrenal cortex make ____ than any other cells because of the size of the zona fasiculata
cortisol
What are some examples of stressors that may cause cortisol secretion?
- heat
- cold
-hypo/hyperglycemia
(not just psychological stress)
Cortisol says “there is a stressful situation, let me throw a bunch of nutrients in the blood” but, a consequence of cortisol is that:
suppresses the immune system
When do cortisol levels spike? What hormone is opposite of this?
early morning hours; growth hormone
Cortisol feedsback and inhibits:
- ACTH secretion from AP
- CRH secretion from hypothalamus
Describe what type of feedback is seen through cortisol:
Long loop
What are the 4 main actions of cortisol?
- Gluconeogenesis
- Protein mobilization
- Fat mobilization
- Stabilizes lysosomes
What action of cortisol leads to the suppression of immune function?
Stabilizing lysosomes
Why are other hormones secreted when ACTH is secreted?
Because the gene for ACTH forms a larger protein (a preprohormone)
What is the name of the preprohormone that ACTH is derived from?
Proopiomelanocortin (POMC)
In addition to ACTH being synthesized from POMC, what else is secreted?
- Melanocyte stimulating hormone (MSH)
- Beta endorphin
- Beta lipotropin
A clinical sign of elevated ACTH pathologically is:
increased skin pigmentation (from melanocytes)
What is a byproduct of ACTH production?
MSH
Cortisol has a similar affinity for the ____ receptor as ____.
mineralcorticoid receptor (MR) as aldosterone
What is found at higher circulating concentrations, aldosterone or cortisol?
Cortisol
Since cortisol is able to bind to the MR receptor, why doesn’t it cause a mineralcorticoid effect?
11B2HSD enzyme converts cortisol to cortisone in aldosterone responsive tissues (making sure the aldosterone binds to the MR receptor, not cortisol)
_____ does not bind to GC or MR receptors with as high of an affinity as _____.
cortisone; cortisol
A genetic deficiency in the 11B2HSD receptor leads to the syndrome:
AME (Apparent Mineralocorticoid excess)
_____ is a compound found in licorice that inhibits the activity of _____.
glycerrhetinic acid; 11B2HSD
What do we expect under normal conditions when the aldosterone binds the mineralocorticoid receptor in the epithelial cells of the kidney?
Increased sodium reabsorption and increased potassium secretion
Where would we find 11B2HSD receptors? Where would we find 11B1HSD receptors?
kidneys, salivary glands, sweat glands
skin
High circulating cortisol levels such as in cushings syndrome can:
Overwhelm the 11HSDB2 enzyme
Both AME syndrome and high circulating cortisol levels will ultimately cause:
High BP
Effects of cortisol on metabolism:
Stimulation of both ___ and _____ in the liver resulting in _____.
gluconeogenesis; glycogenolysis; increases blood glucose
Effects of cortisol on metabolism:
____ action resulting in decreased glucose uptake in the muscle and fat but not the brain or heart.
anti-insulin action
Effects of cortisol on metabolism:
Makes ___ worse by increasing ___ levels, ____ level, and ____ formation and ____ secretion.
diabetes
glucose levels
lipid levels
ketone body formation
insulin secretion
Describe what two hormones are antagonists when dealing with the carbohydrate effect of cortisol on metabolism.
cortisol and insulin are antagonists
Describe what can happen with a diabetic that is scared at the dentist due to cortisol:
They come in, they get stressed out, their cortisol levels rise, in turn their blood sugar rises (because the cortisol stimulates gluconeogenesis and glycogenolysis)
Effects of cortisol on metabolism:
Inhibits ____ synthesis and increases ____ especially in skeletal muscles.
protein synthesis; proteolysis (provides source of AA for glycoenogenesis)
Effects of cortisol on metabolism:
Cortisol excess leads to ___ weakness, pain, ____ skin and abdominal ____ due to the protein catabolic effect.
muscle weakness
thin skin
abdominal striae
Effects of cortisol on metabolism:
promotes ____; and shifts the energy system from utilization of _____ to _____ in times of stress.
lipolysis
glucose to fatty acids
Effects of cortisol on metabolism:
Causes _____ deposition in certain areas (abdomen, interscapular “buffalo hump” and rounded “moon face”
lipid
95% of the glucocorticoid activity of the adrenal cortex is due to the secretion of:
cortisol
Absence of cortisol contributes to _____ due to loss of _____ of ______ on blood vessels
circulatory failure; permissive action; catecholamines
Lack of cortisol also prevents mobilization of _____ (glucose and free fatty acids) during stress and can result in ____.
energy sources; fatal hypoglycemia
Vasoconstriction of blood vessels occurs via:
alpha 1 receptor
Describe the effect cortisol has on catecholamines (alpha 1 receptor) on blood vessels
Permissive effect- the presence of cortisol allows the alpha 1 receptors effect to be maximized
Why would blood pressure decrease when cortisol levels are low?
The presence of cortisol allows the alpha receptors response to be maximized, so without the maximum response, blood pressure would be lower
How does cortisol effect the immune system?
suppresses immune system function
What are few ways that cortisol suppresses the immune system:
- stabilizes the lysosomal membrane
- opposes inflammation (decrease WBC migration and phagocytosis)
- suppresses T-Lymphocytes
What properties of glucocorticoids allows them to be used in treatment of patients with diseases/conditions involving exaggerated inflammatory response?
Their anti-inflammatory action
How can treatment with glucocorticoids cause osteoporosis?
because cortisol stimulates bone resorption via an increase in RANK-L expression by osteoblasts
Treatment with glucocorticoid promotes apoptosis of ____ & ____ which can further lead to osteoporosis.
osteoblasts and osteocytes
The zona reticularis is responsible for the secretion of:
androgens
The zona reticularis begins secreting adrenal androgens around the age ____ , peaking around age _____, and then _____ with age.
age 8, age 20, decreasing with age
Adrenal androgens secreted by the zona reticularis include:
DHEA/DHEAS
Andostenodione
Testosterone
Estrogens
Describe the effects of adrenal androgens in males vs. females:
andrenal androgens have only weak effects in makes but contribute ~50% of active androgens in females
Describe the effects of adrenal androgens in females:
growth of pubic hair, axillary hair, and libido
A condition resulting from excess androgen production in pre-pubertal boys =
precocious pseudopuberty
Normally puberty in boys is stimulated by ___ which leads to the secretion of FSH and LH
But if the adrenal gland is oversecreting androgens it can lead to:
Hypothalamus secreting GRH
early puberty NOT due to the hypothalamic-pituitary axis
If boys are affected by precocious psuedopuberty brought on by excessive androgen secretion from the adrenal gland, this can cause:
early development of secondary sexual characteristics (under age 8)
______ deficiency can result in virilization in newborn females and pseudo-hermaphroditism
21-hydroxylase deficiency
21-hydroxylase deficiency leads to an overproduction of:
androgens (DHEA, DHEAS, Androstenedione)
Androgen secreting tumors producing excess androgen result in: (in females)
virilization and and precocious pseudopuberty in females
Precocious psuedopuberty:
early puberty not caused by HPA secreting GRH and instead due to adrenal androgens in excess
21-hydroxylase is an enzyme critical for making ___ & ____ and in the absence of this enzyme, there is a buildup of ____ & ___ precursors resulting in excessive amounts of _____.
aldosterone and cortisol
aldosterone and cortisol
androgen precursors (DHEA, DHEAS, Androstenedione)
Androstenedione is a precursor to:
testosterone, 5-dihydrotestosterone, and estrogens
Although androstenedione is not the precursor made in the greatest amounts (compared to DHEA and DHEAS), it is the precursor with the:
greatest effect
Why does the precursor androstenedione have the greatest affect (compared to DHEA and DHEAS)?
because it is more readily converted peripherally to testosterone and estrogens
In adults, hormonally active benign adrenal adenomas usually secrete ____ or ____.
aldosterone or cortisol
Virilizing tumors in women are more likely to be caused by:
ovarian tumors
Virilizing adrenal tumors are ___, and virilization is usually due to _____.
rare; hypersecretion of adrenal androgens
List some signs and symptoms of virilizations:
Male pattern baldness, male musculature, clitoromegaly, increased libido, rapid linear growth with advanced bone age
Primary adrenal insufficiency:
Addison’s Disease
Addison’s disease can be caused by primary atrophy or injury to the:
adrenal cortex
In about 80% of Addison’s cases, atrophy occurs due to ______ of all cortical zones
autoimmune destruction
Describe the level of ACTH in Addison’s dx
High ACTH
Describe the levels of corticosteroid production in Addisons disease:
Low corticosteroids
Addison’s disease can be characterized by a loss of:
glucocorticoid, mineralcorticoid and adrogen secretion
Secondary adrenal insufficiency is due to low levels of:
ACTH
IF the pituitary gland is unable to secrete enough ACTH this would result in:
low cortisol production (secondary adrenal insufficiency)
Often latrogenic due to abrupt cessation of steroid therapy:
secondary adrenal insufficiency
What is affected in primary adrenal insufficiency that is not affected in secondary adrenal insufficiency?
mineralcorticoid secretion
Would signs and symptoms of glucocorticoid deficiency be seen in primary or secondary adrenal insufficiency or both?
Would signs and symptoms of mineralocorticoid deficiency be seen in primary or secondary adrenal insufficiency or both?
Would signs and symptoms of adrenal androgen deficiency be seen in primary or secondary adrenal insufficiency or both?
Both- both have lack of cortisol production
primary only
Both- Addisons has loss of androgens; and then secondary has low ACTH leading to low androgen production
Two important symptoms of glucocorticoid deficiency include:
hypoglycemia because normally raises blood glucose
Low BP due to the lack of alpha 1 receptor permissive effect
Hyperpigmentation in primary adrenal insufficiency is due to excess of:
POMC-
Cushings Disease is a _____ disorder characterized by ______.
Cushings syndrome is a _____ disorder characterized by _____.
secondary- occurs due to brain- High ACTH
primary- occurs due to adrenal cortex- low ACTH
Both cushings disease and syndrome is characterized by:
high cortisol levels
Cushings disease or syndrome?
1.secondary disorder:
2. primary disorder
3. due to adrenal cortex
4. due to brain
5. oversecretion of ACTH leads to excessive cortisol level
6. overproduction of cortisol leads to low levels of ACTH
- disease
- syndrome
- syndrome
- disease
- disease
- syndrome
To distinguish between cushings disease and syndrome, what hormone level would you look at?
ACTH
Conn’s syndromes is an issue with ______
Cushings syndrome is an issue with ____
Pheochromocytoma is an issue with ____
mineralcorticoids
glucocorticoids
catecholamines
Sudden release of hormones causing sudden “attack” due to chromaffin cell tumor in the adrenal medulla resulting in excessive secretion of EPI and NE
Pheochromocytoma
What cells are involved in pheochromocytomas?
chromaffin cells
Can be characterized by an exaggerated sympathetic response:
Pheochromocytoma
What hormones are inovled in pheochromocytoma?
Epi and NE
Entire length of thick filament (some overlapping thin filament)
A-band
Includes ONLY thin filaments:
I-band
ONLY thick filaments:
H-zone
Where thin filaments are anchored:
Z-line
Links the central regions of thick filaments:
M-line
When a sarcomere shortens during contraction, what happens to the zone of overlap?
Increases
When a sarcomere shortens during contraction, what happens to the I-band?
Decreases
When sarcomere shortens during contraction, what happens to the A-band?
THE A-BAND DOES NOT CHANGE IN LENGTH
Why does the A- band not change length?
Its the length of the thick filament
Functional unit of skeletal muscle:
sarcomere
The thin filament is composed of what 3 elements?
actin, tropomysin and torponin
What type of actin molecules make up the active site in which myosin binds?
G-actin
What all does troponin bind?
actin, tropomoysin and calcium
Troponin has 3 globular proteins:
T, C and I
The C globular protein of troponin binds to:
calcium
The thick filament is composed of:
Myosin
The myosin filament has multiple cross-bridges where heads can bind to the:
G-actin molecule
Dark band:
A-band
Light band:
I band
In muscle, function as an ATPase enzyme:
myosin
When myosin binds to ATP, what happens?
Hydrolyzes the ATP
What regulate when contracton can happen?
Troponin and Tropomyosin
Protein that connects thin filaments to glycoproteins in the sarcolemma
Dystrophin
Provides scaffolding for sarcomeres:
Dystrophin-glycoprotein complex
What is the difference between Duchenne’s and Becker’s muscular dystrophy?
Duchennes = more severe, low levels of dystrophin if any at all
Beckers= makes some dystrophin but not enough, and because of this muscle cells weaken and die (better prognosis)
List some types of muscular dystrophies:
Duchenne, Beckers, Myotronic, Oclulopharyngeal, and limb girdle
