What are the 3 types of steroids synthesized in the adrenal cortex?
glucocorticoids, mineralocorticoids, androgens, estrogens
What is the function of the adrenal medulla?
composed of chromaffin cells which synthesizes and secretes catecholamines
What are the adrenal glands?
paired endocrine organs consisting of both cortex and medulla
What are the 3 types of adrenalcortical hyperfunction?
hypercortisolism (cushing syndrome), hyperaldosteronism, adrenogenital syndromes(virilizing syndromes)
What is adrenal insufficiency?
is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production
What are adrenocortical neoplasms?
adrenal adenoma and carcinoma
What is pheochromocytoma?
is a neuroendocrine tumor of the medulla of the adrenal glands or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually adrenaline (epinephrine) if in the adrenal gland and not extra-adrenal, and noradrenaline (norepinephrine).
Different cushing symptoms
What is cushings syndrom?
a disorder caused by and condition the produces elevation in glucocorticoid levels
What are the causes of rushings syndrome?
exogenous medications(glucocorticoids), ACTH hypersecretion(pituitary disease), adrenal cortical hyperplasia or cancer, Ectopic ACTH from no pituitary CA(sm. CA lung)
What is the number 1 cause of cushings disease?
ACTH hypersecretion-pituitary disease
is associated with oversecretion of ACTH, variable degrees of bilateral cortical nodular hyperplasia
Characteristics of primary adrenocortical neoplasms and hyperplasia (Cushing's Syndrome)
account for 25-30%, ACTH- independent (adrenals function independently), most cases are unilateral (benign or malignant), nodular hyperplasia is solitary, circumscribed in the adrenal gland
What could potential cause secretions of ectopic ACTH resulting in associated Cushing's Syndrome?
small cell carcinoma of lung, carcinoid tumor, medullary carcinoma of thyroid, islet cell tumor of the pancreas
What is the appearance of the adrenals when subject to ectopic ACTH?
bilateral nodular cortical hyperplasia
clinical features of Cushing's syndrome
hypertension, weight gain, deposition of adipose tissue, hypercortisolosim, gluconeogenesis, protein catabolism (collagen & bone), productions of glucocorticoids, hirsutism, Amenorrhea, Psychosis, hyperpigmentation
Special characteristics of adipose deposition (Cushing's Syndrome)
truncal obesity, round moon face, buffalo hump
Hypercortisolism results in_____ (Cushing's Syndrome).
atrophy of myofibers causing muscle wasting, thin extremities
Gluconeogenesis results in_______ (Cushing's Syndrome).
hyperglycemia, glucosuria, polydipsia
Catabolic effects on protein (collagen & bone) results in what?
loss of collagen and resorption of bone- skin atrophy (easy bruising), striae (purple), and osteoporosis
How does increased production of glucocorticoids affect the body?
suppresses immun system increasing infection rate
Hyperaldosteronism is also known as ?
What is hyperaldosteronism (Conn's Syndrome)?
increased adrenal mineralocorticoids= aldosterone increased
What cellular functions are affected by increased aldosterone?
sodium retnetion and potassium excretion- cuasing hypertension and hypokalemia
What are the two types of causes of Conn's Syndrome? (hyperaldosteronism)?
Primary and secondary
Classify the primary cause of Conn's Syndrome (Hyperaldosteronism)
autonomic over -prodcutions of aldosterone caused by aldosteronoma or primary adrenocortical hyperplasia
Where is aldosterone secreted from?
What does overproduction of aldosterone cause?
suppression of the renin-angiotensin system
what is the secondary cause of Hyperaldosteronism (Conn's Syndrome)?
activation of renin-angiotension system
_____ can be caused by any lesion of the adrenal cortex that impairs corticosteroid production
primary acute adrenocortical insufficiency
Primary adrenal disease can present in what two ways?
1.) acute primary adrenal insufficiency and 2.) chronic primary adrenal insufficiency
Acute primary adrenal insufficiency is also known as _____
Chronic primary adrenal insufficiency is also known as _____.
____ occurs in a variety of settings including a sudden increase in glucocorticoid requirments, rapid withdrawl of steroids, failure to increase steroid doses in adrenal compromized pts, and massive destruction of the adrenals
primary acute andrenocortical insuffiency
____ is a decreased stimulation of the adrenals caused by a deficiency of ACTH
What are things things that may result from secondary hypoadrenalism?
1.) sheehan syndrome 2.) nonfunctional pituitary adenomas 3.) lesions involving the hypothalamus and suprasellar
Primary acute adrenocortical insufficiencies may be caused by ____, ____, and _____.
waterhouse-friderichsen syndrome, sudden pt withdrawl from long-term corticosteroid therapy, stress in pts with underlying chronic adrenal insufficiency
What are four major contributors to primary chronic adrenocortical insufficiences?
1.) autoimmune adrenalitis 2.) TB 3.) acquired immunodeficiency syndrome 4.) metastatic disease
What are four minor contributors to primary chronic adrenocortial insufficiences?
1.) systemic amyloidosis 2.) fungal infx 3.) hemochromatosis 4.) sarcoidosis
Rapid withdrawl of steroids can lead to acute adrenocortical insufficiency bc _______.
there is an inability of the atrophic adrenals to produce glucocorticoid hormones
Acute adrenocortical insufficiencies can be do to massive adrenal hemorrhages that cause what?
parenchyma of adrenal cortex to be damages (maintined on anticoagulant therapy, postop pts-DIC, pregnancy, overwhelming sepsis)
____ is an uncommon condition that occurs most often in adults who suffer destruction of at least 90% of the adrenal cortex.
What are the four causes of Addison Disease?
1.) autoimmune adrenalitis 2.) TB 3.) AIDS 4.) metastatic cancers
______ accounts for 75-90% of Addison Disease cases and it a self-destruction of steroid-producing cells. It can be sporadic or familial disorder and most of the times is restricted to the adrenal gland
Infx's such as ____, ____ and _____ may destroy the adrenals and lead to Addison Disease
TB, histoplasma capsulatum, coccidoides immitis
AIDs pts are at risk for developing Addison Disease from complications with ____, ____ and _____
CMV, mycobacterium avium-intracellulare and Kaposi sarcoma
____ are an uncommon cause of adrenal insufficiency. Common primary tumors include carcinomas of the lung and breats (MCC), GI, and malignant melanomas.
_____ clincally presents with an insidious onset or progressive weakness an easy fatigability, GI (anorexia, N/V, weight loss, diarrhea), hyperpigmentation, and decreased mineralocorticoid activity
Why is hyperpigmentation a clinical presentation in Addison Disease?
the primary disease results in elevated ACTH which is a precursor hormone to melanocytes
One of the clinical features of Addison Disease is decreased mineralocorticoid activity. What is happening?
potassium retention and sodium loss resulting in volume depleteion and hypotension
_____ has the clinical course of intractable vomiting, abdominal pain, hypotension, coma, vascular collapse, and death
Secondary hypoadrenalism cause what two things?
1.) glucocorticoid deficiency and impaired gluconeogenesis
What is a surgically correctible form of hypertension
What is pheochromocytoma?
"Pheochromocytoma is a rare tumor of the adrenal gland that causes too much release of epinephrine and norepinephrine -- hormones that regulate heart rate and blood pressure.
What are the clinical features?
Hypertension- abrupt spikes in BP, headache, diaphoresis, palpitations/tachycardia, tremor and apprehension
Islets of langerhans
1 million microscopic clusters of cells
Endocrine Pancreas is made up of 4 cell types
beta, alpha, delta, PP (pancreatic peptide)
endocrine pancreas beta function
synthesize insulin (most potent anabolic hormone)
Endocrine pancreas alpha cell function
endocrine pancreas delta cell function
endocrine pancreas PP cell function
secretion of gastric and intestinal enzymes, inhibition of intestinal motility
Group of metabolic disorders all with hyperglycemia, chronic disorder of carb,fat, and protein metabolism
hyperglycemia results from
defect in insulin secretion, action, or both
Random Blood sugar 200mg/dl or higher, fasting glucose 126 on more than 1 test, abnormal OGTT with glucose 200 or higher 2 hrs after standard CHO load
normal blood sugar range
Type 2 Diabetes Characteristics
mostly adults, obese, no anti-islet cell antibodies, ketoacidosis is rare, insulin resistance, relative insulin deficiency, no insulitis, focal atrophy and amyloid deposits
Type 1 diabetes characteristics
children, normal weight, decreased blood insulin, anti-islet cell antibodies, ketoacidosis, HLA-D linked, autoimmune, severe insulin deficiency, insulitis early, marked atrophy and fibrosis
Long term sequelae of DM
renal, opthalmalogic, nervous, cardiovascular
Glucose is produced in
glucose uptake and utilization by peripheral tissues
insulin actions and counter regulatrory hormones
DM type more prevelent in children
DM type more prevelent in adults
DM type typically obese
DM type anti islet cell antibodies
DM type ketoacidosis is common
DM type 1 genetics
40% concordence in twins
DM type 2 genetics
60-80% concordence in twins
DM type HLA D linked
DM type that is autoimmune
insulin resistant DM typ
DM type with severe insulin deficiency
DM type with reletive insulin deficiency
DM type with early insulitis
DM type with marked atrophy and fibrosis of islet cells
DM type with focal atrophy and amyloid deposits on islet cells
normal insulin physiology
insulin gene--release from beta cells (biphasic process)---glucose, major anabolic hormone, interacts with its target cells by first binding to the insulin receptors
Primary Insulin function
increase rate of glucose transport, increased synthesis and reduced degredation of glycogen, lipids and proteins
biphasic process for beta cell release
immediate release of insulin stored in granules----delayed and protracted response active synthesis of insulin
Major anaboic hormone
increase the rate of glucose transport to certain cells (myocardial cells, fibroblasts & fat cells) transmembrane transport of glucose and amino acids,glycogen formation, coversion of glucose to triglycerides, nucleic acid synthesis, protein synthesis
What are the target cells and organs for liver?
adipose tissue and muscle, liver
What does an autoimmune attack result in?
beta cell destruction
What are environmental insults?
viral infection, damage to beta cells
What is the pathophysiology of Type 1 DM?
results from autoimmune destruction of beta cells,3 interlocking mechanisms are responsible for the islet cell destruction, B Cell destruction reaches about 90% before classic manifestations develop
What are the 3 interlocking mechanisms responsible for the islet cell destruction?
genetic susceptibility (class 2 MHC), autoimmunity, environmental insult
What are the classic manifestations of type 1 DM?
hyperglycemia and ketosis
Genetic susceptibility of Type 1 DM?
class 2 MHC affects the degree of immune responsiveness to a pancreatic beta-cell autoantigen or a beta-cell autoantigen may be presented in manner that promotes an abonormal ummunolgic reaction
What is autoimmunity of type 1 DM?
overwhelming eveidence implicates autoimmunity and immune meadiated injury as causes of beta cell loss in type 1 diabetes - autoantibodies to B-cell antigens
What are environmental factors of type 1 DM?
essential for the development of autoimmune diabetes, mode of action is not clear, contribute to the immunological mediated erosion of beta cells in individuals with genetic background
What is the pathophysiology of Type 12DM?(2 metabolic defects)
Deranged beta cell secretion of insulin and insulin resistance and obesity
Describe deranged beta cell secretion of insulin
the normal pulsatile, oscillating patterns of insulin secretion is lost and the rapid first place of insulin secretion triggered by glucose is blunted, deposition of amyloid in the islets
What is insulin resistance ?
major cause of development of type 2 DM caused by excess weight, insulin sensitivity of target tissues decreases and serum levels of insulin may be elevated to compensate for the insulin resistance
Most cases see ___________________ followed by increasing degree of B-cell dysfunction?
What is the significance of Obesity w/ type 2 DM?
TNF increased, free fatty acids increas, leptin decreased, resistin increased
What does an increased TNF do?
synthesized by adipocytes and affects postreceptor signaling pathway
What do increased free fatty acids do?
insulin sensitivity decreases
What does decreased leptin do?
adipocyte hormon which is decreased in obesity
What does increased resistan do?
increases insulin resistance while elevated
What are sirtuins?
found to be involved in aging, may improve glucose tolerance, may enhance B-cell insulin secretion
What are some complications of diabetes?
hypergylcemia, microangiopathy, retinopathy, nephropathy, neuropathy, accelerated atherosclerosis
Mechanism of Hyperglycemia
nonenymatic glycosylation, intracellular hyperglycemia with disturbances in polypol pathways
glucose chemically attaches to free amino acid groups of prteins without aid of enzymes
what does nonenzymatic glycosylation cause?
Irreversible advanced glycosylation end (AGE) products--> AGE can bind to many cell type receptors
what does AGE formation on proteins cause?
formation of collagen proteins causes cross-linking btwn polypeptides--> this traps non-glycosylated plasma and interstitial proteins ex) trapped LDL= atherogenesis, trapped albumin= capillary clogs of renal glomeruli
What cell types receptors does AGE bind to?
Endothelium, monocytes, macrophages, lymphocytes, and mesangial cells
What does AGE cell receptor binding initiate?
initiates emigration, cytokine release, increase permeability, & enhances proliferation of fibroblasts and smooth muscle cells
Intracellular hyperglycemia with disturbances in polyol pathways
cells that do not require insulin for glucose uptake will have an increase in intracellular glucose, pushing the polol pathway
glucose + aldose reductse--> fructose + sorbital (polol)
what tissues do not require insulin for glucose uptake?
nerves, lens, kidney, blood vessels
What are the cellular effects of increased sorbitol/fructose?
increase in intracellular osmolarity and influx of water causing osmotic cell injury ex) lens= cataract formation
What are the cellular effects of increased sorbitol?
impairs ion pumps, promotes injury to the Schwann cells and pericytes of retinal capillaries (causing peripheral neuropathy and retinal microaneurysma)