Endocrine Physiology Flashcards
Produces new proteins from DNA
Lipid-soluble
Steroid Hormones
Modifies existing proteins
Water-soluble
Protein hormones
T3, T4, epinephrine, Norepinephrine
Derivative of Tyrosine
Convert hormonal signal into 2nd messenger
G proteins
For fat-soluble substances
Intracellular Receptors
Acts as transducers
G proteins
Is stimulated by Guanine Nucleotide Exchange Factors
GTP-activated
Is inhibited by GTPase-Accelerating Proteins, RGS proteins
GTP-activated
Activates Adenylate Cyclades converts ATP to cAMP -> activates Protein Kinase A
Alpha Subunit of G protein
May regulate ion channels directly
Broken down by cAMP phosphodiesterase
cAMP
Regulates effector proteins
PKA
Alpha t subunit activates cGMP phosphodiesterase -> decreases cGMP -> closes cGMP-dependent ion channels
G protein with alpha t (transducin)
Phospholipids C -> PIP2 -> PIP2 splits into InsP3 or IP3 (releases Calcium from ER) and DAG (activates Protein Kinase C)
G-protein with alpha q
Releases calcium from ER
IP3
activates Protein Kinase C
DAG
Guanylyl Cyclase converts GTP to cGMP -> activates Protein Kinase G -> Phosphorylates Proteins
Receptor Guanylyl Cyclases
Example of Receptor Guanylyl Cyclases
ANP
NO
Attaches to Type 1 subunit-> Phosphorylates Serine/Threonine residues on Type 2 subunit -> activates effectors
Receptor Serine/ Threonine Kinases
Example of Receptor Serine/ Threonine Kinases
TGF-Beta
Example of Receptor Tyrosine Kinase
NGF EGF PDGF IGF-1 insulin
No intrinsic tyrosine kinase activity
Associate with proteins that have tyrosine kinases of the Src family and Janus family (JAK)
Tyrosine-associated Kinase Receptors
Example of Tyrosine-associated Kinase Receptors
EPO
Synthesize in the hypothalamus
CRH
Vasopressin/Oxytocin
cAMP - 2ND MESSENGER
DH (V2 receptors) Angiotensin II (Epithelial cells) Catecholamines (B1 & B2 Receptors) ACTH LH, FSH, TSH HCG MSH CRH Calcitonin PTH Secretin Somatostatin Glucagon
IP3/ DAG - Phospholipase C
ADH (V1 receptor) Angiotensin II (vascular. Smooth muscles) catecholamines (A1 receptors) GnRH TRH GHRH Oxytocin
Steroid Hormone
Aldosterone Cortisol Testosterone Progesterone Estrogen Vitamin D Thyroid Hormone
Tyrosine Kinase
LeptinIGF-1 Insulin EPO GH Prolactin
Guanylate Cyclase Mecanism (cGMP)
ANP
EDRF
nitric oxide
Transport of steroid hormone
Bound to proteins
Active form of steroid hormones
Free, unbound form
Main site of inactivation of hormones
Liver
Mechanism for removal of hormones
Liver
Kidneys
Number of Hormone Receptors - Constant or Variable?
Variable
Minimum amount of hormone to produce effect
1 pictograms per ml
Onset of Hormone Effects
seconds to months
Additive effects of synergistic effects
Epinephrine
NE
Complementary Effects of Synergistic Effects
FSH
Testosterone on spermatogenesis
Permissive effects
Cortisol has permissive effects on Epi & NE with regards to blood vessels
T3 - on Epi with regards to lipolysis
Antagonistic effects
Estrogen blocking prolactin effects on the breast during pregnancy
More common
Hormone has biological actions that, directly or indirectly, inhibit further secretion of the hormone
Negative Feedback (Self-Limiting)
Rare, exploding
Hormone has biological actions that, directly or indirectly, stimulate further secretion of the hormone
Positive Feedback (Self-Augmenting)
Supraoptic Nucleus
Vasopressin
Paraventricular Nucleus
Oxytocin
Give an example of Negative Feedback that does not utilize HPA
Insulin
Give 3 examples of Positive feedback involving hormones
Estrogen-induced LH and FSH Surge
Oxytocin during labor
oxytocin during lactation
Decrease in receptor number or receptor affinity
Down-regulation of Receptors
Example of Down-regulation of Receptors
In uterus, progesterone
T3 down regulates TRH receptors
Increase in receptor number or receptor affinity
Up-regulation of Receptors
Example of Up-regulation of Receptors
Prolactin increases the number of its receptors in the breast
Growth hormone increases the number of its receptors in skeletal muscle and liver
In the ovary, estrogen up-regulates it’s own receptor and that of LH
Lies in the Sella Turcica
Pituitary Gland
Connected to the Median Eminence of the Hypothalamus via pituitary/hypo physical stalk
Pituitary gland
Transmit hypothalamic hormones to the pituitary without passing through the systemic circulation
Hypothalamic-Hypophysial Portal Blood vessels
Adenohypophysis
Anterior Pituitary
Neurohypophysis
Posterior Pituitary
Derived from oral ectoderm (rathke’s Pocuh)
Anterior Pituitary
Basophils cells of Ant. Pituitary
FSH LH ACTH TSH MSH
Acidophilus Cells of Ant. Pituitary
GH
Prolactin
Derived from neural ectoderm (neural outgrowth of Hypothalamus)
Posterior Pituitary
Pituicytes of Post. Pituitary
Vasopressin
Oxytocin
Which of the following is a consequence when the anterior lobe of the pituitary gland is resected?
Inability to stimulate production of thyroid hormone
4 hormones that increase Blood Glucose Level
Epinephrine
GH (acromegaly, gigantism) lead to DM
Cortisol
Glucagon
If pituitary stalk is damaged, all anterior pituitary hormones would decreased, EXCEPT
Prolactin
In terms of number, what are the top 2 cells in the anterior pituitary?
Somatotropin (40%)
Corticotropes (20%)
What are the 3 families of hormones in the anterior pituitary
TSH, LH, FSH ( same alpha unit, unique beta unit)
MSH, ACTH ( derived from POMC)
GH, Prolactin
Both catabolic and anabolic
Growth hormone
Released in pulsatilla fashion (every 2 hours)
Nocturnal Peak: 1 hours after stage 3 or 4 sleep
Growth hormone
Growth hormone
Somatotropin
Stops growth hormone
Somatostatin
IGF
Somatomedin
Mcc of dwarfism
Defect in FGF receptor 3
Achondroplasia
Increased GH
With skeletal deformities
Gigantism
Actions of Prolactin
Lactogenesis
Lactation amenorrhea
Breast development
What is one possible side effects of anti-psychotic drugs that involve Prolactin?
Amenorrhea-Galactorrhea
Prolactin is stimulated by the following
Pregnancy(ESTROGEN) breast ending Sleep Stress TRH Dopamine antagonist
Prolactin is inhibited by
Dopamine, Bromocriptine
Somatostatin
Prolactin (negative feedback)
Aka as ADH or AVP
Vasopressin
Secreted by Supraoptic Nuclei of the hypothalamus
Vasopressin
Responds to ECF changes detected by osmoreceptors in the Organum Vasculosum
Vasopressin
Most potent stimulus of Vasopressin
Increased plasma osmolality
Vasoconstrictor
V1 blood vessels
Water permeability
V2 kidneys
Central DI
URine volume: high
Urine osmolarity: low
ADH levels:low
Treatment: DDAVP (ADH analog)
Peripheral DI
URine volume: high
Urine osmolarity: low
ADH levels: high
Treatment: thiazides diuretics
SIADH
URine volume: low
Urine osmolarity: high
ADH levels: high
Treatment:Demeclocycline (ADH antagonist)
In SIADH, the brain reduces intracellular osmolytes to prevent cell swelling. What happens if you rapidly correct the Hyponatremia?
Osmotic Demyelination Syndrome (esp. In the pons)
From Paraventricular nuclei of the hypothalamus
Oxytocin
Synthesized by the follicular epithelial cells of the thyroid
Thyroid Hormone
T4
93% More half life (6 days) More affinity for binding plasma protein Less (10% of the receptors) binding to nuclear receptor Onset of action: 4x slower (2 days)
T3
7% synthesized Less half life (1 day) Less affinity More (90%) binding receptor) 4x faster (12 hours) onset of action
Thyroxine Binding Globulin (TBG
70%
Transthyretin or Thyroxine Binding Prealbumin (TBPA)
20%
Thyroxine Binding Albumin
10%
Free Thyroxine
0.03%
MIT + DIT
= T3
DIT + DIT
= T4
Iodine trapping
I2
Organic action
MIT & DIT
Coupling
MIT + DIT = T3
DIT + DIT = T4
Storage
Thyroglobulin
Secretion
TSH binding & TSH Receptor
Bone maturation
Bone formation
Thyroid hormone
Growth hormone
IGF 1
Regulation of thyroid hormone secretion is mediated by
TRH & TSH levels
Hyperthyroidism symptoms
Increased basal metabolic rate Weight loss Negative nitrogen balance Increased cardiac output Dyspnea (shortness of breath) Tremor, muscle weakness Exophthalmos - deposition of GAGs and fat Goiter Tibial edema
Hyperthyroidism causes
Graves’ disease
Thyroid neoplasm
Excess TSH secretion
Exogenous T3 or T4
Hyperthyroidism TSH levels
Decreased (feedback inhibition of T3 on the anterior lobe)
Increased (if defect is in anterior pituitary)
Hyperthyroidism treatment
Propylthiouracil
Thyroidectomy
I132
Beta adrenergic blocking agents
Hypothyroidism symptoms
Decreased basal metabolic rate Weight gain Positive nitrogen balance Decreased heat production Cold sensitivity Decreased cardiac output Hypoventilation Lethargy, mental slowness Drooping eyelids Myxedema Growth retardation Mental retardation
Hypothyroidism causes
Thyroiditis Surgery for hyperthyroidism I deficiency cretinism Decreased TRH or TSH
Hypothyroidism TSH levels
Increased (by negative feedback if primary defect is in thyroid gland)
Decreased ( if defect is in hypothalamus or anterior pituitary)
Hypothyroidism treatment
Thyroid hormone replacement therapy
RDA of Iodine per day
150 nanograms
High levels of Iodine inhibiting organize action and iodine thyroid hormone synthesis
Wolf-Chaikoff Effect
Bone age < Chronological Age
Hypothyroidism
Liver and Kidney Failure: TBG levels
Decreased TBG
Estrogen or Pregnancy: TBG levels
Increased TBG
Enzyme that converts T4 to T3
5’ iodinase
T4 can also be converted to
RT3 (inactive)
Aldosterone (mineralocorticoid)
Zone Glomerulosa
Cortisol, corticosterone (Glucocorticoids)
Zone Fasciculata
De-hydro-Epi-androsterone (DHEA) and Androstenedione (weak androgens)
Zone Reticularis
Epinephrine - 80%
NE - 20%
Adrenal medulla
Right adrenal kidney
Pyramidal
Left renal kidney
Crescent shape
Inhibits 11beta-hydroxylase
Metyrapone
Inhibits Desmolase
Ketoconazole
Adrenal androgens in males
Insignificant
Adrenal androgens in females
Significant
Need ACTH for 1st step, but otherwise controlled by RAAS
Aldosterone
Diabetogenic Hormones
Cortisol
GH
Glucagon
Epinephrine
Increases Na reabsorption in the kidneys, sweat glands, salivary glands and colon
Increase K secretion in the kidneys and colon
Increases H secretion in the kidneys
Aldosterone
Oscillates with circadian rhythm
Cortisol
Carbohydrate Effects of Cortisol
Stimulate gluconeogenesis
Increases protein catabolism in muscles
Decreases glucose utilization and insulin sensitivity of adipose tissue
Protein effects in Cortisol
Reduces cellular proteins (except liver)
Increases blood amino acids
Increases liver and plasma proteins
Fat effects of Cortisol
Increases lipolysis
Moon face and buffalo hump
Anti-inflammatory effects of Cortisol
Induces synthesis of lipocortin which inhibits Phospholipase A2 needed for PG and LT synthesis
Stabilizes lysosomal membranes
Decreases migration and phagocytosis of WBC
Suppression of T-lymphocytes
Reduces IL-1, IL2
Increases resolution of inflammation
Blocks inflammatory response to allergies
Decreases eosinophils and lymphocytes
Inhibits histamine and serotonin
Increases RBCs
Dexamethasone Test Cushing syndrome
Cortisol level not suppressed either by low or high dose
Dexamethasone Test Cushing Disease
ACTH and cortisol suppressed by high dose but not low dose
Addison’s disease
Primary adrenocortical insufficiency
Addison’s disease
Hypoglycemia Anorexia, weight loss, vomiting, nausea Weakness Hypotension Hyperkalemia Metabolic acidosis Decreased pubic and auxiliary hair in females Hyper pigmentation
Addison’s disease ACTH levels
Increased (negative feedback effect of decreased cortisol)
Addison’s disease treatment
Replacement of glucocorticoids and mineralocorticoids
Cushing syndrome
Ex. Primary adrenal hyperplasia
Cushing syndrome
Hyperglycemia Muscle wasting Central obesity Round face, supraclavicular fat, buffalo hump Osteoporosis Striae Virilization and menstrual disorders in females Hypertension
Cushing syndrome ACTH levels
Decreased (negative feedback effect of increased cortisol)
Cushing syndrome treatment
Ketoconazole
metyrapone
MCC of exogenous dose of steroid
Cushing syndrome
Cushing disease
Excess ACTH
Cushing disease
Hyperglycemia Muscle wasting Central obesity Round face, supraclavicular fat, buffalo hump Osteoporosis Striae Virilization and menstrual disorders in females Hypertension
Cushing disease ACTH levels
Increased
Cushing disease treament
Surgical removal of ACTH-secreting tumor
Conn Syndrome
Aldosterone-secreting tumor
conn syndrome
Hypertension (inc ECF vol)
Hypokalemia (inc K secretion)
Metabolic acidosis ( inc H secretion)
Decreased renin levels ( inc ECF levels)
Conn syndrome treatment
Aldosterone antagonist (spironolactone) Surgery
21 beta-hydroxylase deficiency
Virility ton in females
Early acceleration of linear growth
Early appearance of public and axillary hair
Symptoms of deficiency of glucocorticoids and mineralocorticoids
21 beta-hydroxylase deficiency ACTH levels
Increased (negative feedback effect of decreased cortisol)
21 beta-hydroxylase deficiency treatment
Replacement of glucocorticoids and mineralocorticoids
17alpha-hydroxylase deficiency
Lack of pubic and axillary hair in females
Symptoms of deficiency of glucocorticoids
Symptoms of excess mineralocorticoids
Hypoglycemia
17alpha-hydroxylase deficiency ACTH levels
Increased (negative feedback effect of decreased cortisol)
17alpha-hydroxylase deficiency treatment
Replacement of glucocorticoids Aldosterone antagonist (spironolactone)
Which of the following statements are true of Cushing’s syndrome except?
A. Pituitary tumors are the most common cause of Cushing’s disease
B. ACTH secreting Tumors can be suppressed by high dose Dexamethasone
C. Exogenous steroids are the most common cause of Cushing’s syndrome
D. NOTA
NOTA
What is the predominant mechanism of hypotension in Addison’s disease?
Decreased responsiveness of Arterioles to catecholamines
Which of the following are expected effects/manifestation of a patient with conn’s syndrome?
Decreased plasma renin level
All of the following substances are decreased in 21 beta-hydroxyl asedeficiency except? A. Deoxycorticosterone B. Aldosterone C. Androgens D. Cortisol
C. Androgens
Glucagon is Synthesizedand secreted by
Alpha cells
Glucagon functions
Mirror image of insulin
Hormone of starvation
Promotes storage of metabolic fuels, mobilization and utilization
Synthesized as pre-glucagon
Glucagon actions
Increase and maintain blood glucose concentration
Major factor stimulating the secretion of decrease blood glucose level
Glucagon
Glucagon secretes what AA?
Arginine and Alanine
Glucagon
CCK - fasting and increase exercise
2nd messenger of Glucagon
CAMP
Delta cells
Somatostatin
Secretion inhibited by insulin via intraislet paracrine mechanism
Inhibit secretion of insulin and glucagon
Modulate or limit the response of insulin and glucagon to ingesting of food
Somatostatin
21 - beta - hydroxylase
Aldosterone: dec COrtisol: dec Androgens: inc ACTH: inc Blood pressure: dec Accumulating substance: 17-hydroxyprogesterone
11 - beta- hydroxylase
Aldosterone: dec COrtisol: dec Androgens: inc ACTH: inc Blood pressure: inc Accumulating substance: 11-deoxy-corticosterone
17-alpha-hydroxylase
Aldosterone: inc COrtisol: dec Androgens: dec ACTH: inc Blood pressure: inc Accumulating substance: pregnenolone
Secretes insulin and Aylin
Beta cells (60%)
Secretes glucagon
Alpha cells (25%)
Secretes Somatostatin
Delta Cells (10%)
Secrete Pancreatic Polypeptide
F cell / PP Cell (5%)
Actions of Insulin
Increases: glucose uptake into the cells Glycogen edits Amino acid uptake into the cells. (For protein synthesis) Lipogenesis and uptake fat deposition Potassium uptake into the cells
Actions of Insulin
Decreases:
Gluconeogenesis
Glycogenolysis
Lipolysis
Actions of glucagon
Increase blood glucose (inc glycogenolysis, gluconeogenesis)
Inc Blood fatty acid and ketoacids
Inc Urea production
Inc Insulin
Actions of Somatostatin
Inhibits both glucagon and insulin to modulate their effects
Inhibits all GI hormones
Stimulated by all types of nutrients
Decreases motility of stomach, duodenum and gallbladder
Decreases both absorption and secretion in the GIT
Side effect of Metformin
Lactic Acidosis
Type 1 crisis
DKA
Type 1 treatment
Insulin
Type 2 crises
HHHS
Type 2 treatment
Weight loss Thiazolidinediones Metformin Sulfonylureas Insulin
Effect of insulin on the brain
None
Insulin: 2nd messenger
Tyrosine Kinase
Glucagon: 2nd messenger
cAMP
Marker for endogenous insulin
C peptide
When proinsulin becomes insulin, what part is cleaved off?
C peptide
GLUT transport is found in Beta Cells
Glut 2
Oral vs IV Glucose: great insulin secretion
Oral glucose
Is more powerful stimulant for insulin secretion because it stimulates the GIP (gastric inhibitory peptide)
Oral Glucose
Type 1
Inadequate secretion:
Inc blood glucose conc
Inc blood fatty acid and ketoacids conc
Inc blood AA conc
Type 2
Down-regulation of insulin receptor on target tissues
Insulin resistance
All of the following insulin secretion EXCPET? A. Hyperglycemia B. Glucagon C. Cholecystokinin D. Alpha adrenergic stimulation E. Gastric inhibitory peptide
D. Alpha adrenergic stimulation
ECF + Chondroitin Sulfate + Hyaluronic Acid
Gelatinous medium
Ground Substance of Organic Matrix
95% of organic matrix
for Tensile Strength
Collagen Fibers
secrete collagen & Ground Substance where calcium precipitates
Osteoblast
Bone Remodelling
Osteoblast
Bone Resorption
Osteoclast
secrete Lysosomal enzymes, citric acid and lactic acid
osteoclast
calcium intake > calcium excretion
Positive Calcium Balance
calcium intake < Calcium excretion
Negative Calcium Balance
hyperreflexia, spontaneous twitching, muscle cramps, and tingling and numbness
Hypocalcemia
constipation, polyuria, polydipsia and neurologic signs of hyporeflexia, lethargy, coma, and death
hypercalcemia
signs of hypocalcemia
chvostek & Trousseau sign
what is the location of PTH receptors
osteoblast
would thyroidectomy cause hypercalcemia due to absent calcitonin?
no, since calcitonin does NOT participate in minute-to-minute calcium regulation
what is the secreted by osteoblast to inhibit osteoclastic activity in hyperparathyroidism?
Alkaline Phosphate
Vitamin D comes from?
Cholesterol
1st activation of vitamin D synthesis
Liver
2nd activation of Vitamin D synthesis
Kidney
secreted by chief cells of the parathyroid gland
PTH
stimulated by hypocalcemia
PTH
also stimulated by hypomagnesemia, except hypomagnesemia caused by alcoholism
PTH
secreted by Parafollicular Cells (C Cells) of the thyroid gland
Calcitonin
PTH in the kidney
increases calcium reabsorption (DT)
decreases phosphate reabsorption (PCT)
increases active vit D
PTH in intestine
none
PTH in bone
increased calcium
decreased phospate
vit D in intestine
increases calcium & phosphate absorption
vit D in Kidney
increases calcium & phosphate reabsorption
increases urinary calcium
vit D in bone
at normal levels: calcium and phosphate deposition
at high toxic levels: calcium & phosphate resorption
PTH net effect on serum levels
increased calcium
decreased phosphate
Vit D net effect on serum levels
increased calcium
increased phosphate
what is the treatment for Humoral Hypercalcemia of Malignancy?
Furosemide ( inhibits renal Ca reabsorption)
Etodronate ( inhibits bone resorption)
presents with short stature, short neck, obesity, subcutaneous calcification, and shortened fourth metatarsals and metacarpals?
Albright Hereditary Osteodystrophy (Pseudohypoparathyroidsm Type Ia)
vitamin D resistance is seen in which condition?
chronic Renal Failure
Which of the following is an action of parathyroid hormone (PTH) on the renal tubule?
a. stimulation of adenylate cyclase
b. inhibition of distal tubule K secretion
c. inhibition of distal tubule ca reabsorption
d, stimulation of proximal tubular phosphate reabsorption
e, inhibition of production of 1,25-dihydroxycholecalciferol
a. stimulation of adenylate cyclase