Flashcards in The Endocrine System Deck (377):
What type of communication is used in the endocrine system?
Amplitude modulated signals
What determines the strength of the signal in endocrine communication?
The amount of the hormone determines the strength of the signal
What type of communication is used in the nervous system?
Frequency modulated signals
What determines the strength of the signal in the nervous system?
The frequency of action potentials produced by neurons
Why is it that endocrine and nervous systems are thought to be inseparable?
Neurohormones secreted by the nervous system act on endocrine tissues
What is the scope of action for the endocrine system?
What is the scope of action for the nervous system?
What is the speed of the endocrine response?
What is the speed of the nervous system response?
Where do autocrine signals act?
On the same cells that secrete them
Where do paracrine signals act?
Diffuse locally and act on neighboring cells
What types of chemical messengers never enter the blood and only communicate from the interstitial fluid?
Autocrine and Paracrine
How do endocrine signals function?
Hormones carried between cells by the blood or other body fluids, bind to specialized receptors on the plasma membrane and induce a response with or without entering the target cell
How do neural signals function?
Diffuse a short distance between neurons
How do neuroendocrine signals function?
They are released from neurons but act on distant cells
What are pheromones?
Hormones released into the environment and act on different individuals
What three feedback mechanisms regulate the synthesis and secretion of hormones of the endocrine system?
Genetically encoded or acquired biorhythms
What is the most common feedback system used in the body to maintain homeostasis?
Negative Feedback System
What is the goal of the negative feedback system?
To have a plasma level of the hormone that feeds back to the hypothalamus to ensure proper levels are maintained
What is the mechanism behind a positive feedback system?
The rate of the process increases as the concentration product increases
How do protein/peptide hormone receptors function?
The receptor is located on the cell surface of the target cell which triggers a response by activating an intracellular enzyme system generating a second messenger
What is the process of signal pathway?
Signal molecule binds to
Receptor protein that activates
Intraceullular signal molecules altering
Target proteins which creates
What is an important aspect of endocrine signaling?
Amplification, the end result is large
What are the two most common second messengers?
cAMP & Ca
What is the predominant effect of second messengers?
Activate protein kinases
What is the general rule of thumb for hormones considered to be peptides or proteins?
All hormones are protein based except those that are secured from the adrenal cortex (steroid hormones)
What are considered amine derived hormones?
What hormones are tyrosine based?
What is the tryptophan derived hormone?
What is unique about the thyroid hormone storage?
There is no storage in the cell, when ready for release, the molecules move to the edge of the cell for exocytosis into the circulation
How do thyroid hormones act like steroids?
Thyroid hormones must be bound to protein in the thyroid follicles
What are characteristics of steroid hormones?
All are lipid soluble and derived from cholesterol or have a chemical structure similar to cholesterol
What are the steroid hormones?
Cortisol, aldosterone, estrogen, progesterone and testosterone
How are steroid hormones stored?
Not stored in discrete secretory granules but are compartmentalized within the endocrine cell and released into the ECF by simple diffusion through the cell membrane
Why is the half life of steroid hormone greater than other hormones?
Al steroid hormones (and thyroid) are bound to transport proteins which increase the half life significantly
What do steroid hormones take so much more time compared to other hormones?
They travel bound to a protein, once reach the correct cell membrane, diffuse across cytoplasm where is binds with the DNA, induces start of transcription. Many mRNA are produced amplifying the signal
What two factors determine hormone clearance?
Rate of secretion into the blood
Rate of removal from the blood
How are hormones cleared?
Metabolic destruction by tissues/target cells
Binding with tissues
Excretion into the bile
Excretion by kidneys into the urine
How are water soluble hormones broken down?
Degraded by enzymes in the blood
What are the two components of receptor modulation?
Up and Down Regulation
What occurs during up regulation of receptors?
Due to a lack of stimulation, neural receptors increase in number
What occurs during down regulation of receptors?
Due to continuous stimulation of a receptor, neural receptors decrease in number
What does the pituitary gland regulate?
Energy and water balance
Response to stress
How many hormones does the pituitary gland secrete?
What does the term trophic indicate?
Act to modulate other endocrine glands, control the function of other tissues
Where is the hypothalamus located?
Floor and lateral walls of the third ventricle
What is the significance of the hypothalamus?
Area of the brain where the endocrine and ANS work together
How is the hypothalamus connected to the pituitary gland?
What surrounds the pituitary gland?
Encased in the sella tunica bounded above by the optic chasm and laterally by the cavernous sinuses
What regulates the anterior pituitary gland?
Negative feedback via hormones from the target organs in the periphery
Where are the four major feedback loops?
LH & FSH ( count as one)
What term is used to describe all of the hypothalamic neuropeptides?
Trophic, releasing hormones that go to the anterior pituitary to release hormones
What part of the pituitary gland has neural connection?
Posterior pituitary gland has direct neural connection
How does the posterior pituitary form?
Downward growth of neural tissues that begins at the diencephalon
How does the anterior pituitary gland form?
Up growth of ectodermal tissue that begins as an evagination of an area of the roof of the mouth
How do the two glands eventually combine?
As the upgrowth expands, it begins to meet the down growth
How does the anterior pituitary gland communicate with the hypothalamus?
Two capillary beds
What is the only hormone of the pituitary gland that is not a trophic hormone?
What are tropes?
Cell of the pituitary gland, specifically the anterior, which manufacture and secrete anterior pituitary hormones
What is the function of growth hormone?
Skeletal development and body growth, regulates protein and CHO metabolism
What is the function of ACTH?
Regulates growth of the adrenal cortex and the release of cortisol and androgenic hormones from the adrenal gland
What is the function of TSH?
Controls growth and metabolism of the thyroid gland and the secretion of thyroid hormones
What is the function of FSH?
Stimulates ovarian follicle, development/spermatogenesis
What is the function of LH?
Induces ovulation and corpus luteum development, stimulates testes to produce testosterone
What is the function of prolactin?
Promotes lactogenesis, inhibits synthesis and secretion of LH and FSH
How does the thyroid gland get stimulates to release T3 and T4?
Thyrotropin releasing hormone stimulates thyrotroph cells of AP gland --> Thyroid stimulating hormone produces and acts on target tissues at the thyroid gland
Where is growth hormones target site?
What is the most common cause of pituitary pathology?
What are the functions of growth hormone?
Decreased insulin sensitivity
What is the effect of growth hormone on the liver?
Insulin like growth factor I released
What are the functions of insulin like growth factor I?
Insulin like activity
Anti lipolytic activity
What is another name for growth hormone inhibiting hormone?
How is growth hormone secreted?
Pulsatile with circadian rhythms
What pathophysiology occurs with excess of growth hormone before puberty?
Giantism, response at epiphyseal plates
What pathophysiology occurs with excess of growth hormone after puberty?
Acromegaly, the diameter increases
What are symptoms typically seen in acromegaly?
Coarsening of facial features, widened fingers, toes, hands and feet, prominent eyebrow ridge and jaws, all organs increase in size
What pathology is present when there is a normal amount of GH but there is low or absent ICF1
How are GH abnormalities diagnosed?
Random GH elevations (know what point of circadian cycle) High normal GH that fails to suppress with glucose administration
Elevated IGF 1 (this does not undergo daily variation)
What airway abnormalities are seen with acromegaly?
Facial deformities, large nose, macroglossia, enlarged thyroid, prognathism, obstructive teeth, hypertrophy of epiglottis, general soft tissue overgrowth and MP 3,4
What cardiac abnormalities are seen in acromegaly?
Arrhythmias, CAD and HTN
What can be done to a patient with Acromegaly to assess from entrapment neuropathies?
How can Octreotide be used in the treatment of Acromegaly?
It is a somastatin analog, inhibits GH secretion by binding to somatostatin 2 and 5 receptors
What drug is a GH receptor antagonist used for treating Acromegaly?
What is typically the cause of giantism?
Noncancerous pituitary tumor
What symptoms are typically seen in giantism?
Large tongue, coarse body hair, skin thickness, heart failure, weakness and visual problems
What is considered dwarfism?
An adult hight of 4'10
What are the two main categories of Dwarfism?
Disproportionate and Proportionate
What are common characteristics of Achondroplasia?
Average torso, shorter arms and legs, OR short trunk with longer limbs
Large head, protruding jaw, crowded and misaligned teeth, double jointed, spine curves forward
How is dwarfism acquired?
Autosomal dominant genetic syndrome
What are the characteristics of proportionate dwarfism?
The body parts are in proportion but shortened (GH deficiency after birth)
What is the function of ACTH?
Regulates the growth of the adrenal cortex and the release of cortisol and androgenic hormones from the adrenal gland
What is one of the most potent activators of the HPA axis?
When does the largest release of ACTH occur during surgical stimulation?
Reversal of anesthesia, extubation and the immediate post operative period
What hormone is released from the adrenal cortex?
Based on circadian rhythms, when is the most amount of cortisol released?
In the morning and during stress
How can ACTH cause hyper pigmentation?
Possesses mild melanocyte stimulating hormone
What is precursor protein that is cleaved to create ACTH?
Pro Opiomelanocortin (POMC)
what controls the release of aldosterone?
Renin --> Angiotensin I --> Angiotensin II
Where does ACTH act in the body?
Acts on the adrenal cortex to release glucocorticoids (cortisol)
What is the process for ACTH to be released?
Hypothalamus --> CRH --> AP --> ACTH
What pathology occurs with hyper secretion of ACTH?
What is typically the cause of Cushing's Syndrome?
Pituitary gland adenoma or over secretion of corticotropin from the hypothalamus
Why might ACTH be increased without the presence of Cushing's syndrome?
Adrenal cortex atrophy, cortisol secretion is reduced and does not close the negative feedback loop
What can occur when there is hypo secretion of ACTH as a primary pituitary disorder?
Results in decreased cortisol secretion from the adrenal cortex (fatal)
What are typically the causes of hypo secretion of ACTH?
Pituitary hyopfunction or failure due to intrapituitary bleed or autoimmune adrenal dysfunction
How could an adrenal adenoma causes hypo secretion of ACTH?
Over secretion of cortisol in the negative feedback loop response
What two hormones are released from the posterior pituitary gland?
Vasopressin and Oxytocin
Where is vasopressin synthesized?
What are the functions of the two vasopressin receptors?
V1 in blood vessels (high concentration in splenic areas) causes vasoconstriction and increased arterial pressure
V2 in kidneys that cause renal fluid reabsorption and increase blood volume
What are additional factors that can cause the release of vasopressin?
At the level of the hypothalamus pain, trauma, nausea, vomiting and increased temperature
What pathology can occur when there is an overproduction of ADH?
Syndrome of Inappropriate ADH (SIADH)
What are symptoms of SIADH?
Water retention, increased urine osmolality, headache, nausea, vomiting altered LOC and death
What is a very serious complication of SIADH?
Water intoxication causing dilutional hyponatremia leading to brain edema
What is the treatment for SIADH?
Correct hyponatremia with caution and restrict fluids
If profound hyponatremia occurs with SIADH what can be given to prevent deterioration?
Hypertonic 3% saline and IV lasix to correct sodium levels slowly
What pathology can occur with underproduction of ADH?
What are common causes of DI?
Trauma, pituitary tumor, surgery or autoimmune
What are symptoms of DI?
Large volumes of dilute urine, dehydration, thirst increased plasma osmolality
What is the treatment of DI?
DDAVP a vasopressin analogue
What is the function of oxytocin?
Stimulates lactation and is thought to help with social affiliation, infant bonding, trust and love
What is the most common cause of hormone pathology?
Anterior pituitary adenoma
What are the three most common types of pituitary adenomas?
Growth hormone (acromegaly)
ACTH secreting (cushings)
What is the presentation of hypopituitarism?
Decreased thyroid function, depressed glucocorticoid production and suppressed sexual development and reproductive function
What are the causes of depletion of pituitary function?
Primary pituitary destruction or destruction of the hypothalamus
What can occur if a pituitary adenoma grows upward?
Compresses the optic chasm which leads to visual changes
What type of visual changes are seen with compression of optic chasm?
Outer peripheral visual loss (bi temporal hemianopsia)
When severe the patient can only see what is in front of them
What is the stalk effect?
Compression of the pituitary stalk may cause elevated prolactin levels and irregular menses
What is Sheehan syndrome?
Postpartum pituitary necrosis (enlarged pituitary gland from pregnancy becomes compressed and necrosis occurs)
What is pituitary apoplexy?
Occurs when pituitary adenomas suddenly bleed internally leasing to an abrupt in size
The tumor can also outgrow its blood supply leading to swelling and dead tissue
What is the treatment of pituitary apoplexy?
Rapid Transphenoidal decompression with consideration of replacement of glucocorticoids and ICP resolution
What symptoms are typically seen in Sheehan Syndrome?
Failure to start post part lactation, increased fatigue, cold intolerance and HoTN unresponsive to volume and pressers
What are the three layers of the adrenal cortex?
What portion forms the bulk of the adrenal gland?
The adrenal cortex
What hormones are secreted from the adrenal cortex?
Secretes Minerocorticoids, Glucocorticoids and Sex hormones
What is the function of the adrenal medulla?
SNS mediation, secretes epi and norepi
What does the Zona Glomerulosa secrete and what controls its release?
Aldosterone which is controlled by Angiotensin II
What is a consequence to the adrenal cortex if there are elevated levels of aldosterone for a prolonged period of time?
Hypertrophy of zona glomerulosa
Why are mineralcorticoids the only hormones released from the zona glomerulosa?
They lack an enzyme required from cortisol synthesis
What is the largest zone of the adrenal cortex and what does it secrete?
Zona Fasciculata which secretes glucocorticoids (cortisol) and a small amount of sex hormones
What is the major controller of cortisol?
ACTH which is released from the anterior pituitary gland
What is secreted from the zona reticularis?
Sex hormones and some glucocorticoids which are stimulated by ACTH
How is cortisol transported in the blood?
Highly bound to corticosterone binding globulin (CBG)
What factors increase CBG production?
Estrogen and pregnancy
What factors decrease circulating CBG?
Liver disease and nephrotic syndrome
What is the most accurate measure of cortisol activity?
What is the plasma half life of cortisol?
Why is cortisol essential for life?
CHO and protein metabolism
Fatty acid metabolism
Electrolyte and water balance
Anti inflammatory and immunosuppressive actions
Normal vascular peremeability
How is cortisol released by the adrenal cortex?
Hypothalamus --> CTRH --> Anterior Pituitary --> ACTH --> adrenal cortex --> cortisol
What are the target cells for aldosterone?
Epithelial cells in the distal convoluted tubule in the kidney to regulate absorption and potassium secretion
What can alter the amount of Aldosterone secreted?
Why isn't ACTH the primary stimulus for aldosterone secretion?
ACTH does not appear to be able to stimulate the enzymes unique to the aldosterone pathway very well
How does sodium intake affect the activity of aldosterone?
Activity of RAAS inversely related to the dietary Na intake and K stimulates aldosterone secretion
What additional factors can cause the release of aldosterone?
ACTH, Na, Dopamine, Beta adrenergic agents
What is the function of Aldosterone?
Reabsorption of sodium and secretion of potassium and hydrogen ions contributing to electrolyte and volume homeostasis
How is the RAAS activated?
Macula densa cells sense low sodium and chloride concentration
Communicate with the Juxtaglomerular cells which sense low volume and secrete renin
Renin splits angiotensinogen to angiotensin I
ACE found in lungs and kidneys converts angiotensin I to angiotensin II
Angiotensin II binds to receptors that cause mineralocorticoid release
What is the rate limiting step in mineralocorticoid and glucocorticoid synthesis?
Cholesterol to pregnenolone
How does etomidate affect glucocorticoid production?
It inhibits Beta 17-hydroxyprogesterone conversion to cortisol
Why is cortisol a vital mediator of the stress response?
It facilitates catecholamine action and secretion thus helping to maintain CV stability
What are the causes of cushing's syndrome?
Endogenous adrenal cortical over secretion OR chronic treatment with glucocorticoids at higher than physiologic doses
What is the typical presentation of Cushing;s syndrome?
Moon-faced, tranquil obesity, skinny extremities, thin skin, easy bruising, osteopenia, fluid retention, HTN, hyperglycemia and DM
What is the most common cause of Cushing's syndrome?
Administration of glucocorticoids for such conditions as arthritis, asthma and allergies
What causes the buffalo hump often seen in Cushing's syndrome?
Redistribution of fat to the back and abdomen
What is the goal of treatment in patients with Cushing's syndrome?
Regulating diabetes and hypertension, ensuring intravascular fluid volume and electrolyte concentrations are normal
What medication can be given to stop potassium loss and mobilize fluids?
What is a major risk of an open adrenalectomy?
What drug can be given to patients with Cushing's syndrome if the effects of carcinoma are not cured by surgery?
Mitotaine, an inhibitor of steroid synthesis
What is the pathology of primary adrenal insufficiency?
Adrenals are unable to produce sufficient amounts of glucocorticoids, mineralocorticoids and androgen hormones
What typically causes Addison's disease?
Autoimmune bilateral adrenal destruction
What are symptoms typically seen in Addison's disease?
Fatigue, weakness, anorexia, nausea, vomiting, hyperpigmentation and hypovolemia
What electrolyte abnormalities are seen in Addison's disease?
Hyponatremia and Hyperkalemia
What causes secondary adrenal insufficiency?
Failure to produce CRH or ACTH caused by HPA disease or suppression
What are the causes of secondary adrenal insufficiency?
Most are iatrogenic:
Exogenous glucocorticoid administration
Pituitary surgery or radiation
What is the only deficit in secondary AI?
Cortisol is the only deficit, aldosterone is not affected therefore there is no hyper pigmentation and only mild electrolyte imbalances are present
What communicable disease is known to cause adrenal insufficiency?
What causes adrenal atrophy?
Chronic administration of steroids
What does a positive ACTH stimulating test indicate?
Demonstrates a poor response to ACTH and indicates an impairment of the adrenal cortex
What is considered absolute adrenal insufficiency?
Low baseline cortisol level and a positive result on the ACTH stimulation test
What is considered relative adrenal insufficiency?
Higher baseline cortisol but positive ACTH test
What dosage of oral prednisone puts a patient a risk for adrenal insufficiency?
Greater than 20mg/day
What dosage of topical or inhaled prednisone puts a patient a risk for adrenal insufficiency?
Greater than 2g/day topical
Greater than 0.8mg/day inhaled
What drug has more mineralocorticoid activity?
Hydrocortisone, methylprednisone has less
How is glucocorticoid supplementation determined for surgery?
Supplementation is individualized based on the surgery
Why is it better to give hydrocortisone compared to methylprednisolone when high doses are required?
Hydrocortisone is less likely to produce fluid retention, edema and hypokalemia
What is the glucocorticoid potency and equivalent dose of cortisol?
Equivalent dose: 20mg
What is the glucocorticoid potency and equivalent dose of cortisone?
Equivalent dose: 25mg
What is the glucocorticoid potency and equivalent dose of prednisone?
Equivalent dose: 5mg
What is the glucocorticoid potency and equivalent dose of Methylprednisolone?
Equivalent dose: 4mg
What is the glucocorticoid potency and equivalent dose of Triamcinolone?
Equivalent dose: 4mg
What is the glucocorticoid potency and equivalent dose of Betamethasone?
Equivalent dose: 0.6mg
What is the glucocorticoid potency and equivalent dose of Dexamethasone?
Equivalent dose: 0.75
What type of patients are at risk for adrenal insufficiency?
Systematic inflammation: TB, HIV, DIC
Etomidate for sedation
How does Conn's syndrome occur?
Functional tumor that acts independently of a physiologic stimulus
What conditions can Conn's syndrome be associated with?
What is the cause of secondary hyperaldosteronism?
Increased circulating renin which stimulates aldosterone release (renovascular hypertension)
What is the primary difference in diagnosing primary versus secondary hyperaldosteronism?
In primary there is suppressed plasma renin activity and in secondary there is elevated plasma renin activity
What are symptoms associated with both primary and secondary hyperaldosteronism?
Spontaneous hypokalemia, systemic hypertension, polyuria, metabolic alkalosis and muscle weakness
What syndrome can mimic hyperaldosteronism?
Licorice syndrome, due to long term licorice ingestion
What is the immediate treatment for primary hyperalsosteronism?
Potassium replacement, administer spironolactone to block aldosterone effect
Potassium sparing and antihypertensive
What are some anesthetic considerations for primary hyperaldosteronsim?
Avoid Sevo if hypokalemic neuropathy and polyuria are present
Hypokalemia may modify response to NDNMBA
Avoid hypoventilation and worsening hypokalemia
Be cautious to over correct volume status, HoTN effects of CV drugs may be magnified
What is another metabolic disturbance seen in hyperaldosteronism?
What does isolated hypoaldosteronism describe?
Lowered aldosterone without corresponding changes in cortisol
What is typically the cause of isolated hypoaldosteronism?
Due to renin or angiotensin II regulation issues (hyporeninemia)
Can be congenital
What are the symptoms of hypoaldosteronism?
Hyperkalemia, acidosis, sodium loss, cardiac conduction defects, volume depletion and HoTN
What is the treatment for hypoaldosteronism?
Mineralocorticoids and glucocorticoids if cortisol deficiency is present
What are the hormones of the adrenal medulla?
Epinephrine, Norepinephrine and Dopamine
What are the physiologic effects of Epinephrine?
Promotes energy mobilization, glycogen converted to glucose, fat to fatty acids
Shunts blood from gut/skin to muscles and bronchodilation
What are the physiologic effects of Norepinephrine?
Neurotransmitter of the sympathetic division of the ANS
What is the breakdown of epi to norepi release from the adrenal medulla?
What type of cells produce the adrenal medulla hormones?
Chromaffin cells principle site where tyrosine is converted to catecholamines
Where do pheochromocytomas arise?
In the chromaffin cells of the adrenal medulla
What is the typical breakdown of catecholamines released when a pheochromocytoma is present?
Where is the most common extra-adrenal location for a pheochromocytoma?
Organ of Zuckerkandl, near the aortic bifurcation
What are the rules of 10s when speaking about pheochromocytomas?
10% Found in children
10% are bilateral
10% are malignant
10% are extra-adrenal
What are the three most common symptoms of pheochromocytoma?
What are the hyperadrenergic symptoms of a pheochromocytoma?
Pressure (elevated BP)
What are patients hyperglycemic with a pheochromocytoma?
Secondary to catecholamine glycohenolysis and insuline release inhibition
What are additional symptoms seen with pheochromocytoma?
What is the most sensitive test for high risk patients if a pheochromocytoma is suspected?
Measurement of plasma free metanephrines
If there is a low probability of pheochromocytoma, what test is done?
Urinary vanillylmandelic acid (VMA) which is a breakdown byproduct of norepinephrine and plasma catecholamines
What are byproducts of catecholamines?
What test is used to determine if a pheochromocytoma is present if the VMA and Metanephrine tests are inconclusive?
Clonidine suppression test
What is the best indicator for a pheochromocytoma?
What is the result if a pheo is present in a clonidine suppression test?
There will be no change in catecholamine levels after Clonidine is given, if no pheo catecholamine level is lower
What is the first line treatment for pheochromocytoma?
What medication is used most frequently in preoperative pheochromocytoma?
Phenoxybenzamine, a long acting non competitive alpha 1 antagonist
Which alpha antagonist is easier to titrate in the treatment of a pheo?
Prazosin, pure alpha 1 competitive blocker
What drug is used in the treatment of a pheo to decrease catecholamine production?
What are the treatment goals for a pheo?
Normotensive, resolution of symptoms and elimination of any EKG changes
What can occur if you over treat a pheo?
Severe orthostatic hypotension
What is the rule of thumb for giving both alpha and beta antagonists in treating a pheo?
ALWAYS give alpha before beta, if you give beta first the patient will have to eject against massive SVR sending patient into heart failure
What drugs should be avoided in pheo surgery?
Histamine releasing drugs and Vasolytics
What actions can induce the release of catecholamines that should be avoided for surgical removal of a pheo?
Fear, pain, shivering, hypercarbia and hypoxia
What is the antihypertensive drug of choice when removing a pheo?
Nitroprusside because it does not act on alpha at all it is a direct smooth muscle relaxant
What drug is preferred for intraoperative HTN in a epi secreting tumor?
Labetalol has beta blocking properties
How can a patient become hypoglycemia intraperatively while removing a pheo?
Decreased catecholamine levels leave insulin unopposed, dextrose containing fluids should be given after tumor removal
What can cause hypertensive episodes when removing a pheo?
What can cause hypotensive episodes when removing a pheo?
Removal, alpha blockade is unmasked
What is Diabetes Mellitus?
A heterogeneous group of disorders that have the common feature of a relative or absolute lack of insulin
What is the pathology of Type I DM?
Associated with T cell mediated autoimmune diseases
There is an insulin deficiency that makes the patient susceptable to ketoacidosis
What is the pathology of Type II DM?
Not immune mediated, susceptible to hyperosmotic non ketotic coma if insulin is deficient
What is the number one cause of blindness, chronic kidney disease and non-traumatic limb amputation in the US?
Where is insulin produced?
Pancreatic beta cells
What is the metabolic affect of insulin?
Where does insulin not influence glucose uptake?
What stimulates the secretion of insulin?
What should occur after a meal in regards to glucose and insulin?
Glucose utilization exceeds glucose production and a transition from exogenous glucose delivery to endogenous glucose production occurs
What are counter regulatory hormones?
Support glucose production and oppose insulins functions
What are examples of counter regulatory hormones?
Glucagon, epinephrine, growth hormone and cortisol
What causes diabetes?
Either an inadequate supply (Type I) or a inadequate tissue response (Type II) to insulin
Where is glucagon produced?
Pancreatic alpha cells and processed in the gut
Where is glucagon receptor location?
In the liver
What causes glucagon production to halt?
What is the function of Glucagon?
Increases breakdown of hepatic glycogen stores and hepatic glucose synthesis
Stimulates fatty acid oxidation and ketogenesis
Stimulates hepatic uptake of amino acids
What type of response can occur when there is multiple hormonal inputs?
Additive or Synergistic
What is a protective mechanism to prevent rapid fluctuations in glucose production?
Push-pull mechanism on the alpha and beta cells of the pancreas
What are the rapid effects of insulin on the body?
Increased transport of glucose, amino acids and K into the insulin sensitive cells
What are the intermediate effects of insulin on the body?
Stimulation of protein synthesis
Inhibition of protein degradation
Activation of glycolytic enzymes and glycogen synthase
Inhibition of phosphorylase and gluconeogenic enzymes
What are the delayed effects of insulin on the body?
Increase in mRNA for lipogenic and other enzymes
What what glucose level does the body inhibit insulin secretion?
At what glucose level does the body secrete glucagon, epinephrine and growth hormone
At what blood glucose level does cortisol secretion occur and the patient experiences cognitive dysfunction?
At what blood glucose level does lethargy occur?
At what blood glucose level does coma and convulsions occur?
At what blood glucose level does permanent brain damage and death occur?
What is the incidence of type I diabetes out of all of the current diabetics?
What is thought to cause type I DM?
Autoimmune pathology, unknown trigger although environmental triggers such as viruses, dietary proteins, drugs or chemicals may initiate the autoimmune process
When does the preclinical period of type I DM occur?
Lasts from 9-13 years and is characterized by production of antibodies to beta cell antigens with loss of beta cell function
When do clinical symptoms begin to manifest in type I DM?
After 80-90% of lost beta cell function
What are the manifestation of type I DM?
Sudden sever onset of hyperglycemia
Intravascular volume depletion
How is diabetes diagnosed?
Fasting glucose greater than 126mg/dL
Random glucose greater than 200mg/dL
HA1C greater than 7
What is the incidence of type II DM out of all diabetics?
What are common themes associated with type II diabetes?
Overweight, resistant to ketoacidosis, susceptible to hyperglycemia, hyperosmolar non-ketotic state
What lifestyle choices are associated with type II diabetes?
Poor food choices
What is the pathophysiology behind type II DM?
A relative beta cell insufficiency and insulin resistance
What is unique regarding the diagnosis of type II DM?
Most people are not diagnosed for approximately 4-7years after the disorder appears
Why dont type II DM patients experience ketoacidosis?
They are making insulin but have a peripheral resistance to it
What are the three important defects in type II DM?
An increase rate of hepatic glucose release
Impaired basal and stimulates insulin secretion
Inefficient use of glucose by peripheral tissues
What causes the increase in hepatic glucose release in type I DM?
The reduction of insulin's normal inhibitory effects on the liver and abnormalities in regulation of glucagon secretion
What is metabolic syndrome?
A constellation of clinical biochemical characteristics frequently seen in patient who have or at risk of developing type II DM
What are characteristics of metabolic syndrome?
Fasting plasma glucose greater than 100mg/dL
Serum triglyceride levels greater than 150
Low serum HDL cholesterol
Blood pressure greater than 130/85
What does the HA1C measure?
Long term glucose control
What is the normal range for HA1C?
At what HA1C puts a patient at risk of microvasculature and microvascular disease?
Greater than 6.5%
What is the first line treatment for DM?
Dietary control and exercise, reduces adiposity and improves hepatic /peripheral tissues insulin sensitiveit, enhances post receptor insulin action and may increase insulin secretion
What pharmacologic treatments can be given for diabetics?
IV or IM insulin preparations
What adverse effects are associated with Sulfonylureas and meglitinides oral anti diabetics?
Delays contractile recovery after myocardial ischemia and expand ischemic zone
What are adverse effects of Metformin?
Lactic acidosis especially with renal insufficiency
How would you calculate a daily dose of insulin for your patient?
kg x 0.3 (divide by 24 if you want an hourly dose)
Why is it essential to have tight control over blood glucose levels?
To prevent continues progression of microvascular complications
What is the pathology of DKA?
A profound loss of insulin production and activity that stimulate lipolysis and fatty acid breakdown which leads to ketosis
What are the primary ketones produced during DKA?
Acetoacetate and beta-hydroxybutyrate
What clinical manifestation occur during DKA episode?
Profound hyperglycemia, polydypsia, polyuria, dehydration, decreased renal blood flow, coma and kussmaul breathing
Why is rehydrating the patient essential in treating DKA?
If insulin is administered in the absence of electrolyte replacement, water will move from the extracellular space back into the cells causing vascular collapse
What are characteristics of hyperglycemic hyperosmolar coma?
Hyperosmolarity and dehydration
How does Hyperglycemic hyperosmolar coma occur?
Precipitated by decreased fluid intake
Why does HHNS cause a higher incidence of coma?
Osmolality may exceed 340mOsm/L
If the plasma osmolality is greater than 320 what can be given for fluid replacement?
Large volumes of hypotonic saline
What type of microvascular complications are associated with diabetes?
Non-occlusive microcirculatory disease and impaired auto regulation of blood flow and vascular tone
What is the most common neuropathy experienced by diabetics?
A distal polyneuropathy
What are symptoms of distal polyneuropathy?
Large sensory and motor fibers
Small fibers areas affect proprioception
Sensitivity to touch pain and temperature is impaired
What is the result of damage to the vasoconstrictor fibers and impaired baroreceptor function in patients with DM?
What are CV symptoms associated with autonomic neuropathy?
Abnormalities in heart rate control (does not respond to exercise)
Systolic and diastolic dysfunction with reduced EF
What GI effects associated with autonomic neuropathy?
Impaired gastric secretion and motility
What is the treatment for gastroparesis?
Small meals, reduced fat content and a prokinetic (reglan)
When should an insulin infusion be initiated for intraoperative use?
Ideally a continuous insulin infusion should be started at least two hours before surgery
What is an appropriate range for glucose intraoperatively?
At what glucose level does glycosuria and dehydration begin to occur?
Greater than 200mg/dL
What is the typical rule of thumb when giving one unit of insulin?
Decreases glucose by 25-30mg/dL
What is the typical dose for an insulin infusion pump?
When does the onset of gestational diabetes typically occur?
During the second half of gestation and resolves at parturition
What is thought to cause gestational diabetes?
Increasing levels of progesterone, cortisol, prolactin and somatotrophin (counter regulatory hormones)
How can gestational diabetes affect the pregnancy?
Associated with an increased rate of C-sections as well as perinatal morbidity and mortality
Who are at risk for gestational diabetes?
Those who have family history of diabetes, especially on the maternal side
Older than 25
Baby more than 9 lbs/ birth defect
Too much amniotic fluid
Overweight before pregnancy
Unexplained stillbirth or miscarriage
Where are thyroidglobulins located?
In the colloid portion of the follicle
What is unique about the action of thyroid hormone?
Although an amine, it enters the affected cell and changes the mRNA like a steroid hormone
If a thyroid deficiency occur, how long might it take to see changes in thyroid levels?
How is T3 and T4 synthesized?
Iodide converted to iodine
iodine attaches to tyrosine on TGP
T3 and T4 formed and TGH is removed in lysosomes
What is the active form of thyroid hormone?
What is the breakdown of thyroid hormone released?
How is thyroid hormone absorbed?
Via ion trapping
How does TSH function to increase the amount of thyroid hormone?
Increases the amount of iodide into the cell for synthesis
Enzyme synthesis via increased DNA transcription of RNA
What protein is T4 bound to?
Thyroid binding globulin
What protein is T3 bound to?
Mainly to albumin
When is thyroid hormone active?
The unbound form
What pathology is associated with an elevated TSH?
What diseases are associated with hypothyroidism?
What pathology occurs when there is a decrease in circulating TSH?
What disease is associated with hyperthyroidism?
How does thyroid hormone exert its affects?
By binding to specific receptors in the nuclei of cells in target tissues
What effects does thyroid hormone have on the body?
Myelination in childhood
What metabolic processes does T3 and T4 stimulate?
Basal metabolic rate
What are the main causes of hyperthyroidism?
TSH secreting pituitary adenoma
What treatment is given to patients with hyperthyroidism?
What is the goal in treating hyperthyroidism?
What are clinical manifestation of hyperthyroidism?
Weight loss, diarrhea, warm moist skin, weakness of large muscles, osteopenia, jittery, heat intolerance, tachycardia, HTN and heart failure
What are the two most common differential diagnoses associated with thyroid storm?
MH and Neuroleptic malignant syndrome
Why should the provider use caution in patients with a history of long term use of amiodarone?
Can cause thyroid storm because it increases plasma thyroid hormone
What are clinical manifestation of thyroid storm?
Hyperpyrexia >40 degrees
Tremors, delirium, apathy
What are triggers for thyroid storm or crisis?
Surgery, infection or trauma
How should thyroid storm be managed?
What drugs should be avoided in thyroid storm?
How does Propylthiouracil treat hyperthyroidism?
It prevents the production of more T3 and T4 in the thyroid and blocks the conversion of T4 to T3 outside of the thyroid
How does Iodides (Lugol's solutionl treat hyperthyroidism?
Blocks release of stored thyroid hormone from thyroid gland
How do glucocorticoids treat hyperthyroidism?
Blocks conversion of T4 to T3
How are beta blockers used in the treatment of hyperthyroidism?
Reduces symptoms caused by heightened response to catecholamine, blocks conversion of T4 to T3
How is Lugol's solution administered?
Via NG tube
What is the mechanism of action of methimazole in treating hyperthyroidism?
Prevents production (synthesis) of more thyroid hormone
What term is used to describe fetal hypothyroidism?
What are clinical presentations of hypothyroidism?
Slow mental function
intolerance to cold
slow gastric emptying
If hypothyroidism is left untreated what is the end result?
What are clinical manifestations of Myxedema Coma?
Typically seen in elderly obese females
Become increasingly withdrawn, lethargic, sleepy and confused
Slip into coma
What findings in a patients history may cause concern for Myxedema coma?
Previous thyroid surgery
Default hormone therapy
What is the most common reason for hypothyroidism to occur?
Previous thyroid surgery thyroid adenoma
What diagnostic test is typically used in determining thyroid pathology?
What are some anesthetic implication for patients undergoing a thyroidectomy?
Must be euthyroid preoperatively
Thorough airway assessment
Avoid drugs that stimulate the SNS
What are the main airways concerns in patients with goiters?
Vena Caval obstruction if tumor extends into the chest
What are some intraoperative considerations for patients having a thyroidectomy?
Avoid premedication/use regional when possible
Protect against hypothermia
Where are the parathyroid glands located?
Four glands on the posterior aspect of the thyroid gland
What lab value is often drawn when removal the of thyroid gland has occurred?
Ionized Calcium due to removal of the thyroid gland
What stimulates the release of parathyroid hormone?
How does hypercalemia affect PTH?
Suppresses both hormonal synthesis and release of calcium
How does PTH maintain normal plasma concentration of calcium?
Promotes the movement of calcium across three interfaces
What is required in order for the parathyroid gland to function?
What is the active form of vitamin D?
What hormones promotes the storage of calcium?
Why is calcitonin said to be counter regulatory to PTH?
It inhibits bine mobilization and lowers blood calcium
What is typically the cause of primary hyperparathyroidism?
What is typically the cause of secondary hyperparathyroidism?
Inadequate D3 produced, hypocalcemia stimulates hight PTH levels
What are clinical manifestations of hyperparathyroidism?
Dehydration, bone pain, confusion, anorexia, constipation, muscle weakness, HoTN, shortened QT
What is the most common cause of primary hypoparathyoidism?
Surgical parathyroid resection
What arecommon causes of secondary hypoparathyroidism?
Reduced vitamin D
Chronic renal insuffiency
Acute systemic illness
What drugs have been known to cause hypoparathyroidism?
What are clinical presentations of hypocalcemia?
Muscle cramping Seizures
What two signs are used to determine if hypocalcemia is present?
What is the most common post op complication associated with removal of the parathyroid glands?
Tetany, be aware if the patient develops stridor can be cord tetany
What may cause refractory hypocalcemia after removal of the parathyroid glands?