PHCL Exam 2 Flashcards
Hypothalamic-Pituitary-Adrenal (HPA) Axis
stress -> hippocampus -> hypothalamus ->(release of CRH)-> anterior pituitary -> (release of ACTH) -> adrenal cortrex -> (release of cortisol)
zone of fasciculata
cortisol and androgens
enzyme = CYP11B1 & CYP17
zone of glomerulosa
enzyme = CYP11B2 -> aldosterone
zone of reticularis
cortisol and androgens
enzyme = CYP11B1 & CYP17
adrenal medulla
epinephrine and norepinephrine
enzyme = CYP17 -> DHEA
glucocorticoids
cortisol = affects metabolism and immune function
in blood binds to corticosteroid - binding globulin
mineralocorticoids
aldosterone - salt retaining
causes sodium resorption in distal renal tubule, sweat glands, salivary glands, GI
Deoxycorticosterone
secreted precursor to Aldosterone
glucocorticoids effect on the body
increase glucose production
increase muscle atrophy
increase bone loss
increase lipolysis
increase anti-inflammatory genes
decrease proinflammatory
Adrenergic or Estrogenic hormones
Sexual maturity and characteristics
Cortisol can feed back to the pituitary and hypothalamus to
reduce further stimulation of the system (feedback inhibition)
diurnal cycle of serum glucocorticoids
lowest in the middle of the night, but peaks in the morning – probably helps with waking.
No average difference between girls and boys, age, puberty, etc., but a lot of variance in the individual levels of glucocorticoids
Corticosteroids
regulate energy metabolism
increase short-term memory (good for learning/tests!), maintain bp, inhibit inflammation,
help with fetal lung development.
anitarthirists
Repeated stress can lead to
habituation
but some forms of chronic stressors (e.g., severe pain, blood loss, hypoglycemia)
can lead to no habituation. In both cases a novel stress can cause a hyper-response of the HPA axis
Addison’s disease
Corticosteroid deficiency
Causes low blood sugar, low bp, weakness, muscle/joint pain, skin darkening or vitiligo, salt craving (reduced salt, increased potassium) nausea/diarrhea, depression. These can be very dangerous if not controlled.
Cushing’s Syndrome
Corticosteroid overload
Skin thinning, depression/mood swings, memory loss/learning disability, muscle wasting, poor wound healing/suppressed immune system, hypertension, diabetes, osteoporosis, anovulation
Cortisone
was isolated in the 1940s and used for rheumatoid arthritis for the first time in 1948 – quickly became a widely used drug.
therapeutic vs adverse effects of glucocorticoid
therapeutic= anti-allergic, decrease pain swelling stiffness physical disability
adverse = cataract glaucoma, increased cardiac risk, osteonecrosis and osteoporosis, infections
clinical causes for both Addison’s disease
adrenal glands not function
-autoimmune disease
clinical causes for both Cushing’s syndrome.
-too much HPA activation
-tumor maybe
-can be born or develop when older
Glucocorticoids regulate 10-20% of genes in your body by
Bind to glucocorticoid receptor (GR) inside cells – can be alpha (active) or beta (blocks alpha)
Glucocorticoids bind with great affinity
to corticosteroid binding globulin (CBG) in plasma – not very well to albumin
in the cell, glucocorticoids bind to their receptor, cause
dimerization, translocate to the nucleus and bind to DNA to regulate transcription of target genes
Regulation of genes by the GR can either involve
transactivation of target genes, or transrepression (messing up other transcription factors). Net result is increase in anti-inflammatory gene expression, decrease in pro-inflammatory gene expression
Cortisone
was isolated from cows in the 1940s and used for rheumatoid arthritis for the first time in 1948 – quickly became a widely used drug.
Biological Activities of Corticosteroids
-energy metabolism
-stimulate gluconeogenesis
-inhibit glucose uptake by muscle or adipose tissue (because brain needs the glucose)
-increase serum glucose levels
-increase short term memory
alpha cells
release glucagon. Stimulates breakdown of glycogen to produce glucose (liver, muscle)
beta cells
release insulin, C-peptide, amylin. Insulin stimulates glucose uptake into cells
delta cells
release somatostatin
G cells
release gastrin
F cells
release pancreatic peptide release
Therapeutic insulin
Different half lives. Drives glucose uptake
Exenatide
LP-1 receptor agonist, blocks glucagon release
Pramlintide
binds amylin receptors to decrease appetite)
Octreotide
(mimics somatostatin, blocks growth hormones,
glucagon and insulin)
Cleavage of pro-insulin by proprotein convertases
create functional insulin and its by-product, C-peptide
DPP-4 inhibitors
DPP-4 is an enzyme that breaks down GLP-1 in the body. Inhibiting this enzyme allows for more
GLP-1, so more insulin release
GLP-1 receptor agonists
GLP-1 stands for glucagon-like peptide-1. Receptor is found on beta cells. GLP-1 receptor agonists decrease glucagon and increase insulin.
Sulfonylureas
diabetes drug (close K+ channels)
Metformin
diabetes drug that target AMPK or AMPkinase which inhibits glucose production in the liver
in the Biguanides class of drug
A1C
a measure of glycation of blood hemoglobin
insulin
A peptide hormone produced by beta cells of the pancreas, and is central for regulating carbohydrate and fat metabolism
glycogen
polysacchairde
glucagon
peptide hormone produced by alpha cells of the pancreas
glucose
small molecule
understand the role of the pancreas in glucose metabolism and which types of pancreatic cells are involved
the pancreas has the islets of langerhans which are the alpha cells, beta cells, and delta cells
the alphas cells secrete glucagon which increase blood glucose
the beta cells secrete insulin, C-peptide, amylin that lower blood glucose
the delta cells secrete somatostatin
the g cells secrete gastrin
the f cells secrete pancreatic polypeptide
Function of Secreted Products of Pancreatic Cells
glucagon = hypoglycemic factor that mobilizes glycogen stores
Insulin = the storage and anabolic hormone
Amylin = modulate appetite, gastric emptying, glucagon and insulin secretion
Somatostatin = inhibitor of secretory cells, growth hormone inhibitor
Gastrin = stimulate gastric acid secretion
what it means to be insulin resistant
Two major variants of insulin receptor abnormalities associated with acanthosis nigricans have been described—the classic type A insulin resistance syndrome, which is due to an absent or dysfunctional receptor, and type B insulin resistance syndrome, which results from autoantibodies to the insulin receptor (very rare)
Understand the effects of insulin on muscle, liver and adipose tissue
insulin effect on muscle :
increase protein synthesis
increase amino acid transport
increase ribosomal protein synthesis
increase glycogen synthesis
increase glucose transport
INDUCES glycogen synthase and inhibits phosphorylase
insulin effect on liver :
reversal of catabolic features on insulin deficiency
inhibits glycogenolysis
inhibits conversion of fatty acids to keto acid
inhibits conversion of amino acids to glucose
anabolic action = promotes glucose stage as glycogen
increase triglyceride synthesis and VLVL
insulin effect on adipose tissue:
increase triglyceride storage
Define diabetes mellitus, know the four different types
elevated blood glucose associated with absent or
inadequate pancreatic insulin secretion, with or without impairment of insulin action
Type 1: insulin-dependent diabetes, selective beta cell destruction, insulin deficiency
Type 2: non-insulin dependent, tissue resistance to insulin, relative deficiency of insulin
Type 3: other, such as pancreatectomy, pancreatitis, drug therapy
Type 4: gestational diabetes mellitus, placental hormones cause insulin resistance
understand the root causes and symptoms of type 2 diabetes.
over time you have insulin resistance
-age
-inactivity
-high lipid levels
-over wight
-family history
Cleavage of pro-insulin by proprotein convertases (enzymes
create functional insulin and its by-product, C-peptide
GLUT 2 transporter on beta cells
glucose goes into GLUT 2 transporter on beta cells leads to ATP least to blockage of potassium channel leads to opening of calcium channel leads to vesicles release insulin
GLUT 4 transporter
insulin leads to insulin receptor on muscle / fat leads to signaling lead to translocation on GLUT 4 vesicles membrane
all increase blood glucose levels
Food, glucagon and glucocorticoids
fasting versus prandial state
fasting blood sugar is taken before eating a meal and your postprandial blood sugar is taken after the meal
GLP-1 receptor agonists
GLP-1 stands for glucagon-like peptide-1. Receptor is found on beta cells. GLP-1 receptor agonists
decrease glucagon and increase insulin
DPP-4 inhibitors
DPP-4 is an enzyme that breaks down GLP-1 in the body. Inhibiting this enzyme allows for more GLP-1, so more insulin release.
Sulfonylureas
(close K+ channels), GLP-1 Receptor Agonists, DPP-4 inhibitors
