Module 6 - Endocrine system Flashcards
Def: endocrine system
Body system which uses hormones to communicate and send messages.
regulated byt NEGATIVE feedback loops
Some Endocrine glands
*Hypothalamus
*Pituitary
Thyroid and parathyroid Glands
Adrenal Glands
Pancreas
Ovaries / Testes
Exocrine function of the pancreas?
Secretes digestive enzymes directly into the GI tract
Endocrine function of the pancreas?
Secretes hormones from the islets of langerhans
insulin - from Beta cells
Glucagon - from Alpha cells
what is released in response to HIGH blood sugar?
*what is its job?
Insulin
- promotes the uptake, utilization and storage of glucose –> lowers blood glucose concentration
what is released in response to LOW blood sugar?
*what is its job?
Glucagon
- increases the hepatic glucose glucose output –> increased blood glucose concentration
what is Glycogen?
Stored Glucose.
MOA: insulin
“the storage hormone” - promotes anabolism and inhibits catabolism of carbohydrates, fatty acids, and proteins
- suppresses endogenous glucose
- inhibits glucagon release
- causes rapid uptake, storage and use of glucose by insulin sensitive tissue - muscle, liver, adipose, brain
usual amount of Insulin secreted in a day
25-50 units
basal release rate of insulin
0.5-1.0 units/hour
when would the rate of insulin release increase?
when blood glucose levels are >5.5mmol/L (in response to eating)
beta cells secrete small amounts of insulin throughout the day?
Basal insulin release
At meal times, insulin is rapidly released in response to food
Bolus insulin release
Def: diabete Mellitus
A metabolic disorder characterized by the presence of hyperglycaemia due to defective insulin secretion, insulin action, or both.
Type 1 Diabetes
Due to defective insulin secretion
An autoimmune destruction of pancreatic Beta cells causing an absolute lack of insulin secretion
Type 2 Diabetes
Due to insulin resistance, eventually leading to defective insulin secretion
Macrovascular complications of Diabetes
Cardiovascular disease (dyslipidemia, hypertension, coronary artery disease, stroke, erectile dysfunction)
Microvascular complications of diabetes
- Nephtopathy leading to kidney impairment leading to kidney failure.
- Retinopathy potentially leading to blindness
- peripheral neuropathy leading to infection and possible amputation
signs and symptoms of Type 1 Diabetes
Hyperglycemia polyuria polyphagia polydipsia glucosuria weight loss fatigue
Diabetic ketoacidosis (DKA)
The body breaks down ketones for energy instead (because it can’t use glucose) leads to production of kept acids, coma, and death
Signs and symptoms of Diabetic Ketoacidosis
Nausea vomiting severe abdominal pain this excessive urine production dry mouth hypotension tachycardia deep and laboured breathing (acetone) confusion ketones present in urine
Fasting Blood Glucose level
“technically” no caloric intake for at least 8 hrs.
post- prandial blood glucose level
taken 2 hours AFTER a meal
Hemoglobin A1C (%)
Measures an average of of blood glucose over the last 3 months
target values for A1C (adults >18)
less than or equal to 7.0% (for most)
Taget values for Fasting glucose levels
4.0-7.0
target values for Post Prandial Blood glucose
- 0-10.0
5. 0-8.0 if A1C targets not being met
Signs and symptoms of Hyperglycemia
Fasting blood glucose >7.0 mmol/L polyuria polydipsia polyphagia glucosuria fatigue
Treatment of Type 1 diabetes
Insulin - by giving insulin we try to obtain glucose homeostasis
MOA: Insulin detemir
Long-acting insulin analogue
- after injection the molecules self-associate and bind to albumin, and are slowly released from subcutaneous tissue into blood stream. slow predictable rate.
MOA: Insulin glargine
Long-acting insulin analogue
- An acidic (pH of 4) product in the vial, and once injected subcutaneously, the acidic solution is neutralized and forms micro-precipitates. these slowly dissolve over at a slow predictable rate.
what colour would a bolus insulin solution be?
Clear
What colour would a basal insulin solution be?
cloudy - except Lantus and Levemir
place these insulin administration site in order of fastest to slowest speed of absorption
- arm
- buttock
- abdomen
- thigh
- abdomen
- arm
- thigh
- buttock
would absorption increase or decrease with exercise?
it would increase
would absorption increase or decrease with cold?
it would decrease
how long can open vials of insulin be stored at room temperature for?
28 days
which insulins should not be mixed with any other insulins?
Long acting insulin analogues
When mixing 2 insulins, which should always be drawn up first?
the quick acting (bolus) insulin should always be drawn before the long acting (basal) insulin
what is the dawn phenomenon?
A natural increase in blood glucose that occurs 4-8am
du to in glucose production by liver and hormone sugars in morning in response to circadian rhythm - unpredictable and inconsistent
what is the Somogyi effect?
An increase in blood glucose caused by the liver producing glucose in response to hypoglycaemia during the night.
signs of hypoglycaemia during the night?
Nightmares
sweating
hunger
headache upon waking
Hypoglycemia
Fasting glucose < 4 mmol/L
LOW blood glucose. can occur if too much insulin given, improper timing of insulin, or pt skipped a meal.
Signs and symptoms of Hypoglycemia - autonomic
Trembling palpitations sweating anxiety hunger tingling
Signs and symptoms of Hypoglycemia -Neuroglycopenic
Difficulty concentrating confusion weakness drowsiness vision changes difficulty speaking headache dizzeness
ways to reverse hypoglycemia
15grams of simple carbohydrates
- 4, 4g glucose tablets
- 15mL water with 3tsp of sugar
- 175mL juice or regular soft drink
- 6 lifesavers
- 15mL (1 tablespoon) of honey
Signs and symptoms of Type 2 diabetes
- MAYBE polyuria, polydipsia, nocturne, fatigue
- CAN be asymptomatic at diagnosis
- often overweight or obese
- May have already developed complications
Classes of Oral HupOglycemics
- Metformin
- Sulfonylureas
- Meglitinides
- Thiazolidinesdiones
- Acarbose
- Incretins
- SGLT-2 Inhibitors
MOA: Metformin
A biguanide
enhances tissues sensitivity to insulin which reduces insulin resistance - also decreases hepatic gluconeogenesis
Adverse effects: Metformin
nausea(take with food), diarrhea, lactic acidosis (rare)
- does not cause hypoglycaemia on its own.
Lactic acidosis
an accumulation of serum lactate which lowers blood pH
signs and symptoms of lactic acidosis
weakness malaise fatigue myalgia heavy laboured breathing
MOA: sulfonylureas
Enhances insulin secretion from the pancreas (insulin secretagogue) - also increases insulin sensitivity at target tissues (like metformin)
Adverse effects: sulfonylureas
Hypoglycemia weight gain nausea rash hepatotoxicity (do NOT take with alcohol) - avoid in elderly - can cause hypoglycaemia on its own
MOA: Meglitinides
Stimulate release of insulin from pancreas. (insulin secretagogue)
* requires presence of glucose to exert action, therefore MUST be take before (within 30min) or WITH a meal.
Adverse effects: Meglitinides
generally only cause hypoglycaemia when combined with another hypoglycaemic drug
MOA: Thiazolidinediones
Enhance insulin sensitivity at target tissues (similar to metformin)
food has no direct effect (can be taken with or without food)
adverse effects: Thiazolidinediones
Edema and fluid retention, headache, weight gain
- may increase risk of fractures, some concerns about increased cardiovascular events
not likely to cause hypoglycaemia on its own
MOA: Acarbose
Inhibits Alph-glucosidase, which blocks absorption of carbohydrates from the GI tract, preventing hyperglycaemia - must be taken WITH meals
Adverse effects: Acarbose
Abdominal cramping
diatthea
flatulence
malabsorption of vitamins/ minerals or other drugs (separate by 2 hrs)
potential hepatoxicity
- does not cause hypoglycaemia on its own
* if hypoglycaemia DOES occur - must not take SUCROSE - only use GLUCOSE tabs, milk, or honey.
MOA: Inretins
- two potential aims
incretins are hormones that tell the pancreas to release insulin (from pituitary)
- mimic endogenous incretin (GLP-1 agonists) OR
- inhibit the breakdown of incretin (DPP-4 inhibitors)
- mimic endogenous incretin (GLP-1 agonists) OR
Adverse effects: Incretins
nausea
vomiting
diarrhea
edema
some concerns about pancreatitis, pancreatic cancer, and cardiovascular disease
* not likely to cause hypoglycaemia on its own
MOA: SGLT-2 inhibitors
Increases excretion of glucose in kidney, therefor reducing blood glucose levels
Adverse effects: SGLT-2 inhibitors
weight loss diuretic effect hypotension polydipsia (thirst) increased rate of UTIs MUST have adequate kidney function* Not likely to cause hypoglycaemia on own
Diabetes Monitoring considerations
Blood glucose levels Hemoglobin A1C Signs of hypoglycaemia and hyperglycaemia BP and pulse Kidney function Tingling, numbness, checking feet Vision Liver Enzymes
stimulates the basal metabolic rate of nearly all tissues.
Thyroid gland
Over-Abundance of thyroid hormone
Hyperthyroidism
Inability to produce thyroid hormone
hypothyroidism
Signs of Hyperthyroidism
Tachycardia and palpitations
hypertension
nervousness, irritability, insomnia, tremor
weight loos despite large appetite
hyperglycaemia
heat intolerance and hyperthermia, fever, sweating
eyelid lag, protruding eyes, goiter
Signs of hypothyroidism
Bradycardia hypertension then hypotension gradual onset of weakness and fatigue, muscle cramps weight gain despite decreased appetite hypoglycaemia cold intolerance and hypothermia dry skin and hair, delayed reflexes
What can be a cause of hypothyroidism?
Iodine deficiency. because thyroid hormone contains iodine
classes of medications for Hypothyroidism
- thyroid agents
A. levothyroxine (T4)
B. Other thyroid products
classes of medications for hyperthyroidism
- Anti-thyroid agents
A. Propylthiouracil
B. Methimazole
C. Radioactive Iodide
MOA: Levothyroxine
Synthetically made T4 hormone which the body converts to T3 in peripheral tissues as needed.
- best absorbed on an empty stomach, 1/2 hour before eating, or 2 hours after eating.
- take in morning
some other thyroid products
Liothyronine (Synthetic T3) Desiccated thyroid (mix of T3 and T4 obtained form dried thyroid glands from pigs)
MOA: propylthioutacil (PTU)
Inhibits synthesis of thyroid hormone, as well as conversion of T4 to T3
*used short term to control thyroid function until surgery
Adverse effects: propylthioutacil (PTU)
rash symptoms of hypothyroidism agranulocytosis hepatotoxcitiy many drug interactions must be take multiple X/day can take up to 3 wks to exert effect.
MOA: Methimazole
Inhibits synthesis of thyroid hormone, but does NOT inhibit T4 conversion.
*safe than propylthioutacil, but takes longer to work.
taken once daily
Long-term option
MOA: radioactive Iodide
Iodine is only taken up by the thyroid. radioactivity destroys the thyroid gland. goal is to only destroy a little of it - but many result in hypothyroid state.
* can also treat thyroid cancer.
Monitoring: Thyroid disorders
Adverse effects r/t replacement therapies are RARE
monitoring focuses on symptoms of HYPO and HYPER thyroidism and the effectiveness of therapy
adherence and consistent administration
proper adjustment of doses.
What hormones are secreted by the Adrenal Glands?
Epinephrine and Norepinephrine
Mineralocorticoids - aldosterone
Glucocorticoids - Corticol
Androgens - DHEA –> testosterone
released in response to stress (sympathetic nervous system activation)
* job is to bring body back to homeostasis
Cortisol
Adverse effects: Corticosteroids - opthalmic
Stinging redness tearing buring secondary infection *Long-term use - cataracts, glaucoma
Adverse effects: Corticosteroids - Oral inhalation
Thrush hoarsness dry mouth dysphoria (change in voice) dysphagia taste disturbance
Adverse effects: Corticosteroids - nasal inhalation
Rhinorrhea buring sneezing dry mucous membranes epistaxis loss of smell
Adverse effects: Corticosteroids - topical
burning
irritation
skin atrophy
telangiectasia
How to prevent adverse effects from corticosteroids ?
Lowest dose possible for shortest duration possible. apply very thin layer of product only on affected area, do NOT apply to open skin.
Adverse effects: Corticosteroids with systemic administration CNS EYE FACE/TRUNK HEART GI BLOOD KIDNEYS GROWTH MUSCLE BONES SKIN
CNS: Euphoria, insomnia, restlessness, increased appetite, altered mood,
EYE: cataracts, glaucoma
FACE/TRUNK: Redistribution of fat leading to moon face (Cushings), buffalo hump, protruding abdomen
HEART: hypertension, enlarged heart
GI: stomach upset, may increase risk of ulcer.
BLOOD: glucose intolerance leading to diabetes
KIDNEYS: fluid retention
GROTH inhibition. use cautiously in children
MUSCLE: wasting of muscle tissue
BONES: osteoporosis
SKIN: easy bruising, poor wound healing, acne, striae
continuous presence of cortisol (or anything that use cortisol receptor) inhibits what feedback cycle?
HPA axis - Hypothalamus Pituitary Adrenal Gland Axis
consequences of HPA-Axis Suppression?
If needed in a true emergency, it cannot produce cortisol to bring the body back to homeostasis
Purpose of Pulse therapy
To induce remissions of serious conditions (MS, Lupus, Rheumatoid arthritis)
disadvantages of pulse therapy
More likely to see hypertension, hyperglycaemia, secondary infections, and psychosis
advantages of pulse therapy
rapid control, lower cumulative doses, less long-term adverse effects
MOA: Prednisone
mimics endogenous cortisol, reducing inflammation and suppressing immune system
indications: prednisone
For sever inflammation, exacerbation of auto-immune diseases
adverse effects: prednisone
nausea, hypertension, hyperglycaemia, insomnia, psychosis, redistribution of fat, osteoporosis, easy bruising, infections, HPA-Axis suppression
*use short term whenever possible
what does each Nephron consist of?
Glomerulus Bowman's capsule Proximal Tublule Loop of hence Distal Tubule Collecting duct
functions of the kidney
Excretory: filtration, secretion, reabsorption, excretion
Endocrine: renin, prostaglandins, kinins, erythropoietin secretion
Metabolic: Vitamin D activation, Gluconeogenesis, Insulin metabolism
6 functions of the kidneys
- regulate fluid, electrolyte, and acid-base balance
- remove metabolic waste products from blood for urinary excretion
- removal of foreign chemicals from blood for urinary excretion
- regulation of blood pressure
- secretion of hormones
- Gluconeogenesis
Progressive loss of kidney function occurring over several month to years. characterized by gradual replacement of normal kidney architecture with fibrosis.
kidney disease
how do we monitor kidney disease?
Serum Creatinine and calculate the creatinine clearance - and estimate of GFR
GFR and metabolic consequences for stage 1 kidney disease
GFR Greater than or equal to 90. no obvious consequences.
GFR and metabolic consequences for stage 2 kidney disease
GFR 60-89
decreased calcium absorption and increased parathyroid hormone
GFR and metabolic consequences for stage 3 kidney disease
GFR 30-59
hypocalcemia, malnutrition, onset of anemia, onset of left ventricular hypertrophy
GFR and metabolic consequences for stage 4 kidney disease
GFR 15-29
increased triglycerides, hyperphosphatemia, sodium/water imbalance, metabolic acidosis, tendency to hyperkalemia, hypermagnesiumia
GFR and metabolic consequences for stage 5 kidney disease
GFR less than 15 or RRT (renal replacement therapy)
Development of azotemia (retention of urea and nitrogenous wastes in the blood)
interventions to delay progression of kidney disease
- BP control
- ACE-inhibitors /ARB therapy - indicated for Pt’s with CKD in the ABSENCE of hypertension
- Tight bloot glucose control for dabetics
- smoking cessation
- Avoidance of Nephrotaxins
medications for kidney disease
Diuretics (loop) Sodium Bicarbonate sodium polystyrene sultanate phosphate binders, calcium, vit D Erythropoietin and iron Cardiovascular drugs GI drugs Neurologics
withdrawal of progestin
causes menses
maintenance of Progestin
Maintain a pregnancy
Regulate uterine changes
Progestins
responsible for maturation of sex organs and secondary sex characteristics of female
Estrogens
other important metabolic effects of estrogens
Maintain cholesterol levels involved with clotting factors facilitating calcium uptake into bones maintaining healthy vulvovaginal tissue sexual motivation maintaining skin collagen, elasticity and thickness decreased gingival inflammation
MOA: Contraceptions
Delivers small doses of estrogen and progestin or progestin alone to provide negative feedback, inhibiting ovulation from occurring (preventing LH and FSH spike)
adverse effects associated with estrogen
Nausea breast tenderness headache bloating thrombosis
Adverse effects associated with progestins
irritability fatigue breast tenderness bloating withdrawal bleeding headache adverse lipid alterations PMS-like symptoms
MOA: mifepristone
potent progesterone receptor modulator, with strong antiprogestin and antiglucocorticoid activity
causes endometrial degeneration, uterine contractility, resumption of prostaglandin production. cerviacla softening and dilation, potential onset of bleeding
MOA: misoprostol
potent synthetic prostaglandin, induces cervical ripening, uterine contractions, acts on GI smooth muscle.
Menopause
An age related decrease in number and quality of ovarian follicles - they no longer respond to FSH
- ovaries no longer produce estrogen or progestins
pituitary initially response with increased levels of FSH and LH *peri-menopause
*12 consecutive month with NO menses
Short term Menopausal symptoms
Vasomotor symptoms (photoflashes) sleeping pattern changes (insomnia) Mood and cognition changes Genitourinary changes (vulvovaginal atrophy) Sexual changes (loss of libido) Bleeding changes (irregularity)
Long term menopausal symptoms
Osteoporosis - decline in estrogen causes increased in bone turnover and reabsorption
CVD
Hormone replacement therapy in NOT recommended solely for the purpose of preventing either osteoporosis or CVD
why is estrogen given with progesterone for Hormonal replacement therapies and Oral contraceptives?
Estrogen cause proliferation of the endometrial lining, it the lining does not get sloughed off the in an increased risk of endometrial cancer in postmenopausal women.
Selective Estrogen Receptor Modulators
Can act as both estrogen agonist and antagonist, depending upon the site of the receptor
MOA: raloxifene
an agonist on bone and lipid receptor. preventing osteoporosis and hypercholesterolemia, but an antagonist on uterine nd great tissue
MOA: tamoxifen
a competitive antagonist in breast and uterine tissue which displaces endogenous estrogen (a stimulating factor for some cancers) and likely and agonist on bone endometrial and lipid receptors
MOA: clomiphene
Stimulates release of LH, which matures more ovarian follicles
MOA: human chorionic gonadotropin (HCG)
Identical to human LH, matures ovarian follicles - levels detectable inuring
MOA: Progestins
Presence help maintain pregnancy - can give vaginally if frequent miscarriages in early stages
Def: endometriosis
Presence of endometrial tissue in the locations besides the uterus. Tissue responds to Estrogens and progestins, causing severe pain, dysfunctional bleeding, and dysmenorrhea when soughing occurs
MOA: Leuprolide
GnRH agonists that initially increase, then eventually suppress HPO-axis
MOA: Danazol
Pituitary gonadotropin inhibitor, suppresses HPO-axis
Functions of Androgens
Build muscle mass
promotes synthesis of erythropoietin
maturation of male sex organs and responsible for secondary sex characteristics of men.
adverse effects from anabolic steroid use: MEN
Raise cholesterol levels hepatotoxicity aggression tumour altered glucose tolerance impotence low sperm counts
adverse effects from anabolic steroid use: women
Raise cholesterol levels hepatotoxicity aggression tumour altered glucose masculine appearance (irreversible deepening of voice and facial hair development) menstrual irregularities
2 factors involved with Benign prostatic Hyperplasia
- enlargement of prostate due to androgens (DHT)
2. decline in detrusor muscle strength (Alpha1 receptors) in bladder due to age
Benign prostatic Hyperplasia - causes
occurs when the enlarged prostate starts to push against the urethra, restricting flow of urine. the bladder wall then begins to thicken and become irritable.
MOA: Alpha1-Blockers
Receptos in both Smooth muscle or bladder, urethra, and prostate - relax the smooth muscle, easing urgency symptoms and possibly restriction.
*improve but do not eliminate symptoms
adverse effects: Alpha1-Blockers
Retrograde ejaculation
dizziness, fatigue, rhinitis
orthostatic hypotension
syncope
intraoperative floppy iris syndrom (dilates pupil)
Needs dosage adjustment for liver or kidney dysfunction
MOA: 5-Alpha-reductase inhibitors
Block conversion of testosterone into DHT
CAN change prostate size.
adverse effects: 5-Alpha-reductase inhibitors
Ejaculatory dysfunction loss of libido impotence gynecomastia can cause birth defects in male children (why it is important to handle med appropriately!)
MOA: Phosphodiesterase-5 inhibitors (PDE-5-I)
Enhance nitric oxide-induces smooth muscle relaxation which allows blood flow into corpus cavernous.
must NEVER be given in addition to nitrate (potent vasodilators)
Adverse effects: Phosphodiesterase-5 inhibitors (PDE-5-I)
Hypotension, headache, back and muscle pain, hearing loss, visual changes, priapism (erection lasting more than 4 hours)
