Unit 3 Pathophysiology - Chapter 22 Alterations of Hormonal Regulation Flashcards
Endocrine abnormalities
- decrease in number of receptors
- receptor insensitivity to hormone
- present antibodies against specific receptors
- 2nd messenger defects or postreceptor defects
SIADH (Syndrome of inappropriate antidiuretic hormone)
- abnormally high ADH secretion
- interfere w/ renal free water clearance
- l/t hyponatremia and hypoosmolality
- assocaited with forms of cancer, ectopic secretion of ADH by tumor cells
SX
* oliguria
* concentrated urine (very little output)
* edema + body weight
* pulmonary edema w/ dyspnea and fatigue
* CNS disturbances - n/v, cramps, twitching, lethargy, confusion, seizure, death
DI (diabetes insipidus)
- neurogenic (inadequate response to ADH)
- low ADH secretion
- failure to concentrate urine w/ polyuria and polydispsia
SX
* Polyuria
* dilute urine (pee alot)
* signs of dehydration - hypotension, tachycardia, dry mucuos membrane
* CNS - confusion, dec LOC, irritability
Dipsogenic polydipsa
- compulsory water drinking
- lowers plasma osmolarity to point that it falls below threshold for ADH secretion
Hypopituitarism
- anterior pituitary dysfunction
- failure of hormonal functions
Causes
* pituitary infarction (obstruction of bloodflow)
* space-occupying lesions (tumor or aneurysm)
* surgical removal
* infection
May have these common sx
* short height
* infertility
* cold intolerance
* fatigue
* cannot produce breast milk
Hyperpituitarism
- caused by pituitary adenomas (benign slow growing tumors that arise from cells of the anterior pituitary)
Possible common sx
* weight loss
* heat intolerance
* anxiety
* mnestrual disturbances
* palpitations
Pituitary adenoma complications?
- neurologic and secretory effects
- Pressure from tumors:
1. hyposecretion of cells
2. dysfunction of optic chiasm (l/t visual disturbances)
3. dysfunction of hypothalamus and some cranial nerves
Hypersecretion of GH
- Adults - acromegaly (too much GH, causing bones, cartilage, body organs and other tissues to increase in size) [pituitary adenoma is common cause]
- Children - gigantism
GH deficiency
- Children - growth failure and fastying hypoglycemia
- Adult - fatigue, osteoporosis, and increased mortaility
Thyrotoxicosis
- general condition in which TH levels are elevated produced an exaggerated resposne
- heat intolerance
- palpitations
- anxiety
- fatigue
- weight loss
- muscle weakness
- irregular menses
Hyperthyroidism
- increased circulating TH and stimulation of SNS
SX
* Weight loss
* Increased appetite
* Increased body temp
* Heat intolerance
* Tachycardia
* Palpitations/arrhythmias
* HTN
* diarrhea
* anxiety/irritability/insomnia
* sweating / skin thinning
* hair growth (fine soft hair)
* onycholysis (nail separates from nail beds)
* goiter (enlarged)
* bulging eyes (inflamed eyes)
Graves disease
- form of hyperthyroidism
- caused by thyroid-stimulating immunoglobulins (autoimmune)
- diffuse thyroid enlargement, d/o of skin and eyes
Losing weight without trying.
Fast heartbeat, a condition called tachycardia.
Irregular heartbeat, also called arrhythmia.
Pounding of the heart, sometimes called heart palpitations.
Increased hunger.
Nervousness, anxiety and irritability.
Tremor, usually a small trembling in the hands and fingers.
Sweating.
Changes in menstrual cycles.
Increased sensitivity to heat.
Changes in bowel patterns, especially more-frequent bowel movements.
Enlarged thyroid gland, sometimes called a goiter, which may appear as a swelling at the base of the neck.
Tiredness.
Muscle weakness.
Sleep problems.
Warm, moist skin.
Thinning skin.
Fine, brittle hair
Toxic multinodular goiter and solitary toxic adenoma
Hyperplastic (increased # of cells), hyperfunctioning thyroid nodules autonomously secrete TH — hyperthyrodism and producing sx similar to Graves disease
Toxic multinodular goiter result from multiple fx adenomas
Thyrotoxic crisis
- Thyroid storm
- Often associated with physiologic stress
- W/o treatment, death occurs quickly
Hypothyroidism
- deficient production of TH by thyroid gland
- causes of primary version: iodine deficiency, autoimmune thyroiditis (hashimoto thyroiditis — via cell and antibody-mediated immune processes), subacute or painless thyroiditis (antithyroid antibodies, hyper => hypo, resolve itself within a year?), postpartum thyroiditis, and iatrogenic hypothyrodism (treatment for hyperthyroidism causes suppression of T4 below normal levels)
sx
* Decreased energy metabolism
* thinning hair
* loss of eyebrow hair
* brittle nails
* puffy face
* enlarged thyroid
* dry + coarse skin
* slow heartbeat
* poor appetite
* infertility / heavy menstruation
* constipation
* cool extremities w/ swelling of limbs?
* muscle or joint pain
* weight gain
* poor memroy
* cold intolerance
* feeling of tiredness
* depression + irritabiilty
Hashimoto or autoimmune thyroiditis
Associated w/ lymphocyte infiltration => antibody activation of natural killer celss => induce apoptosis w/ gradual loss of thyroid function => hypothyroid
Subacute thyroiditis
- self limited nonbacterial inflammation of thyroid gland
- damages follicular cells => cause leakage of triiodothyronine (T3) and thyroxine (T4); hyperthyrodism then transient hypothyroidism => corrected by cellular repair and return to normal levels in thyroid
Secondary hypothyroidism
- caused by hypothalamic-pituitary dysfunction in which TRH and TSH are not produced in sufficient amounts
Thyroid carcinoma
- cause ionizing radiation (especially childhood)
Myxedema
- characteristic sign of hypothyroidism
- alterations in connective tissue w/ water-binding proteins
- this excess water l/t thickened mucuos membranes + edema => around eyes and hands/feets (swelling of underlying tissue causing waxy consistency)
- can be life threatening
Congenital hypothyrodism
TH deficieny @ birth d/t thyroid agenesis (total lack)
* hypothyrodism, growth failure, intellectual disability d/t absence of thyroxine
Papillary and follicular thyroid carcinomas
common thyroid malignancies particulary during childhood d/t ionizing radiation exposure
* thyroid nodules present with normal thyroxine levels
Hyperparathyroidism
Greater than normal secretion of PTH
* caused by parathyroid adenoma (primary hyperparathyrodism, usual cause)
sx include:
* chronic hypercalcemia, increased bone resorption (bone breakdown), and hypercalciuria (excess calcium in urine)
* osteoporosis
* kidney stones
* excessive urination
* stomach pain
* tiring easily or weakness
* depression and forgetfulness
* bone and joint pain
* c/o illness no apparent cause
* n/v and no appetite
Secondary hyperparathyroidism
- Compensatory to hypocalcemia
- Often occurs with chronic renal failure or chronic vitamin D deficiency (vitamin D helps with gut absorption of ca++ and maintains optimal serum calcium + phosphate for normal bone mineralization (growth + remodeling by osteoblasts and osteoclasts // without vitamin D bones get brittle or thin)
Lack of vitamin D activation in kidneys d/t CKD l/t hypocalcemia and hyperphosphatemia => compensate via PTH => 2ndary
Tertiary hyperparathyrodism
- excessive secretion of PTH and hypercalcemia that occurs after long-standing hypocalcemia
Psuedohypoparathyroidism and familial hypocalciuric hypercalcemia
- Former - resistance to PTH (inherited condition)
- Latter - inherited too, cause abnormally high serum ca++ and low to moderate level of ca++ in urine w/ high normal to mildly elevated parathyroid hormone
sx:
* weakness
* faitgue
* poor concentration
* polydipsia (excessive thirst)
Hypoparathyrodism
- low PTH levels (d/t surgery, autoimmunity, genetic mechanisms)
- low serum calcium, increased serum phosphate, dereased bone resorption, and EVENTUAL hypocalciuria
Calcium and phosphate relationship
Within the body calcium and phosphate are inversely related: as blood calcium levels rise, phosphate levels fall. This is because phosphate binds to calcium reducing the available free calcium within the bloodstream.
Type 1 diabetes
- immune type (type 1A) – genetic susceptibility, environmental factors, and autoantibody, T-cell, and macropahge destruction of pancreatic beta cells w/ loss of insulin production + excess of glucagon
- Furthermore: antibodies can be formed against glutamic acid decarboxylase (catalyses the production of GABA, a major neurotransmitter of the central nervous system // GABA — islet cell fx, glucose homeostasis, autoimmunity) and insulin
- Type 1b occurs secondary to other disease
Type 2 diabetes mellitus
- Genetic susceptibility triggered by environmental factors
- most compelling factors: obseity
- insulin production continues but weight and number of beta cells decrease
- Furthermore, amylin deficiency l/t increased glucagon secretion and hyperglycemia
Amylin regulates glucose homeostasis by inhibiting gastric emptying, inhibiting the release of the counter‐regulatory hormone glucagon and inducing meal‐ending satiety
Insulin resistance and diabetes 2 causes?
Decreased ghrelin (hunger hormone, plays role in growth hormone, and insulin management), low amylin levels, and decreased beta-cell response to glucagon-like peptide
Amylin inhibits food intake, delays gastric emptying, and decreases blood glucose levels, leading to the reduction of body weight.
Other specific types of diabetes mellitus
- MODY (Maturity-onset diabetes of the young) d/t autosomal dominant gene mutations => similar to type 2
- gestational diabetes d/t onset of glucose intolerance during pregnancy
DKA (Diabetic ketoacidosis)
- insulin deficiency + increase in counterregulatory hormones (glucagon, catecholamines, cortisol) causing body to metabolize triglycerides and amino acids instead of glucose for energy. Serum glycerol and free fatty acids rise d/t unrestrained lipolysis. Alanine increases d/t muscle catabolism. Glycerol and alanine => source for hepatic gluconeogenesis (stimulated by excess glucagon)
- Glucagon stimulates mitochondrial conversion of free fatty acids into ketones (insulin typically blocks ketogenesis via stopping transport of fatty acid derivatives into mitochondrial matrix, but proceeds here d/t lack of insulin). Ketoacids produced (acetoacetic acid and beta-hydroxybutyric acid) => metabolic acidosis => acetone accumulates and slowly disposed by respiration
- Osmotic diuresis => immense loss of Na+ (can rise too d/t too much loss of free water) and potassium (chance for hypokalemia, initially hyperkalemia d/t migration of potassium out the cell d/t acidosis)
- Common in diabetes type 1, but can occur in type 2
SX:
* N/V, abdominal pain
* lethargy, somnolence (drowsiness)
* Hypotensive and tachycardic d/t dehydration and acidosis
* dry skin and mouth
* thirsty/urinating alot
* Kussmaul respirations (compensate via rapid breathing for acidemia) ==> fruity breath d/t acetone
* Coma and death
* Acute cerebral edema in 1% => primarily children
* blood pH <7.3
* above 250 mg/dl
* ketones +
TX: IV fluid and insulin
Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)
- similar to DKA
- lower free fatty acid
- lack of ketosis => indicates level of insulin is present
- Hyperosmolar state (>600 mg/dl) => osmotic diuresis and profound dehydration => coma
//////////////////////////////////////////////////////////////////////// - frequent urination
- extreme thirst
- dry mouth
- confusion or sleepiness
- skin warm/dry no sweating
- fever
- trace ketone
- > 7.3 pH
- 10-20% mortality
- common in type 2 diabetes
- develops slowly within days to weeks
- commonly w/ infections => pneumonia, UTI, sepsis
euglycemic diabetes-related ketoacidosis (euDKA)
DKA with blood sugar less than 250 mg/dl
Hypoglycemia
lowered blood sugar r/t exogenous (insulin shock), endogenous or functional causes
sx
Looking pale Shakiness Sweating Headache Hunger or nausea An irregular or fast heartbeat Fatigue Irritability or anxiety Difficulty concentrating Dizziness or lightheadedness Tingling or numbness of the lips, tongue or cheek
As hypoglycemia worsens, signs and symptoms can include:
Confusion, unusual behavior or both, such as the inability to complete routine tasks
Loss of coordination
Slurred speech
Blurry vision or tunnel vision
Nightmares, if asleep
Severe hypoglycemia may cause:
Unresponsiveness (loss of consciousness) Seizures
Somogyi effect
combination of hypoglycemia at early morning hours with rebound hyperglycemia (GH, cortisol, and catecholamines caused by counter-regulatory hormones (most common in persons w/ type 1 dm and in children) mainly in morning
* d/t taking too much insulin or not eating a regular bedtime snack
Dawn phenomenon
- similar to somogyi effect
- d/t body’s natural reaction to hormones (cortisol, growth hormone, catecholamine) released as morning approaches => release large amount of sugar
- nocturnal elevations of GH // not sugar related entirely
Chronic complications of diabetes mellitus
- microvascular disease (retinopathy [preventable blind, caused by damage to light sensitive tissue at back of eye, sx: blurred vision], neuropathy [weakness, numbness and pain from nerve damage in hands or feet], and nephropathy [deterioration of kidney function])
- Macrovascular disease (CAD, stroke, peripheral vascular disease [narrowed vessels])
- Infection
Metabolic changes contibuting to DM complications?
- oxidative stress
- shunting of glucose to polyol pathway (30% glucose consumed via this process, glucose reduced to 1) sorbitol then to 2) fructose.
- Hyperglycemia activates PKC (protein kinase C) => increasing connective tissue growth factor and transforming growth factor-beta (TGF-B) l/t mesangium expansion [smooth-like muscle cells w/ actin and myosin crucial in filtration of glomerular bloodflow] and nephromegaly [enlarged kidney] => ultimately glomerular sclerosis (scarring) and diabetic nephropathy
- formation of AGEs (advanced glycation end products) or Glucose (a type of sugar) molecules in the blood normally become stuck to hemoglobin molecules => proteins and lipids glycated after sugar exposure => causes diabetic vasculature and artherosclerosis
- accumulation of hexosamines (important in glucose uptake, glycogen synthesis, glycolysis and GF synthese) ===> excess l/t insulin resistance
Microvascular complications r/t elevated sugars
- Alterations to endothelium and basement membrane (extracellular matrix behind endothelium - biochemical + mechanical signaling, tissue integrity, elasticity, and intracellular and intercellular interactions)
- thrombosis
Diabetic retinopathy
- microvascular change + thrombosis l/t occlusion, retinal ischemia, increased vascular permeability, micro aneurysm formation, hemorrhage, and neovascularization w/ loss of vision
Diabetic nephropathy
- r/t hyperglycemia, hyperperfusion, oxidative stress and inflammation
- glomerular enlargement and glomerular basement membrane thickening (bulbs and surrounding bulbs is the membrane)
- intercapillary glomerulosclerosis (scarring of filtering part of kidney => glomerulus)
- mesangial matrix expansion [mesangium]
- progressive renal failure
Diabetic neuropathies
- vascular and metabolic mechanisms
- axonal and Schwann cell (glial cell surrouding neurons covering them myelin sheath (PNS) keeping them alive) degeneration
- abnormal sensory and motor nerve conduction velocity
- involves ANS
Macrovascular disease and DM
- associated w/ high sugar, high lipids, inflammation, and altered endothelial fx
CAD and stroke in diabetes
- consequence of accelerated atherosclerosis (buildup of plaque in artery)
- HTN and increased risk of thrombus (clot may stay in place and grow until blocks blood or break free then becoming a embolus creating a blockage in another vessel via embolism causing HA, stroke, PE) formation
Peripheral artery disease
- consequence of neuropathy
- occluding of large/small arteries resulting in further ischemia, necrosis, and amputation
Other uniques risks of diabetic patients
- impaired WBC and suppressed immunity
- delayed wound healing
Adrenal medulla vs adrenal cortex
Adrenal cortex makes:
* aldosterone (mineralcorticoid)
* cortisol (glucocorticoid)
* estrogen and androgen (sex hormones)
Adrenal medulla (center) makes:
* epinephrine (adrenaline) and norepinephrine (noradrenaline)
Hypofunction of adrenal medulla
no known disorders associated
Hypercortisolism (cushing’s)
Cushing disease or ectopic ACTH syndrome (ACTH-dependent)
- excessive anterior pituitary ACTH production b/c of an ACTH-secreting pituitary microadenoma (commonly)
- This syndrome occurs d/t high levels of cortisol regardless of cause (exogenous - administration of glucocorticoids // endogenous forms - 1) corticotropin dependent usually caused by ACTH-secreting pituitary tumor OR 2) corticotropin independent cause (adrenal cortical tumor)
- LOSE diurnal (daily) and circadian patterns of ACTH and cortisol release
- Lack ability to increase secretion of these hormones in response to stressors
- Other sx: weight gain, glucose intolerance, protein wasting, bone disease, hyperpigmentation, and immunosuppression
- larger trunk w/ thin arms and legs + moon face
- buffalo hump? fatty lump between shoulders (back)
- thin skin, slow healing
- hirsutism (thick black hair on face + body), skin darkening
- irregular period
- HTN
- lethargy, muscle weakness
- insomnia, depression/irritabiilty, poor sex drive
- stunted growth, infections
- Don’t forget this is a…. CATABOLIC hormone yikes
Congenital adrenal hyperplasia
Autosomal recessive disorder
* Inadequate synthesis of cortisols — glucocorticoids (LOW)
* Increased levels of ACTH => causing adrenal hyperplasia l/t overproduction of mineralocorticoids or androgens
Primary hyperaldosteronism
- disorder - high levels of aldosterone caused by adrenal cortical adenoma (benign) or bilateral nodular (cyst, carcinoma, lobule of normal tissue, or other lesion) hyperplasia
- hyperaldosteronism type 1 (rare autosomal dominant disorder)
SX
* HTN, hypokalemia, renal potassium wasting, neuromuscular manifestations (headache, muscle weakness, muscle spasm, paralysis), urinating often/feeling thirsty
Secondary hyperaldosterone secretion
- elevated renin
- activation of angiotensin II (vessel vasoconstriction)
Other potential causes
* decreased circulating volume OR decreased renal blood supply
* elevated estrogen level (influences RAAS)
* Bartter syndrome is a renal tubular salt-wasting disorder in which the kidneys cannot reabsorb sodium and chloride in the thick ascending limb of the loop of Henle (l/t mild volume depletion => increasing renin and aldosterone release => urinary potassium and hydrogen losses
* Renin-secreting tumors
//////////////////////////////////////////////////////////////////////////////////
SX
* HTN, hypokalemia, renal potassium wasting, neuromuscular manifestations (headache, muscle weakness, muscle spasm, paralysis), urinating often/feeling thirsty
Adrenal tumors w/ sex hormone regulation
- Adenomas (benign) and carcinomas
- can autonomously secrete androgens or estrogens
Hypofunction of adrenal cortex
- affect glucocorticoid and/or mineralocorticoid seceretion
- caused by ACTH deficiency or by primary deficiency in the GLAND itself
Hypocortisolism
- low levels of cortisol
- inadeqaute ACTH produciton or by primary cortisol hyposecretion
Addison disease
- elevated ACTH levels w/ inadequate corticosteroid synthesis and output
Caused by: - idiopathic autoimmune disease (destroying adrenal cortex, sparing medulla)
- tuberculosis of adrenal gland
- familial adrenal insufficiency
- amyloidosis (produced in bone marrow) => accumulate in adrenal gland d/t hereditary or inflammatory diseases
- metastatic destruction of adrenal glands
- adrenal hemorrhage
manifestations
* hypocortisolism
* hypoaldsoteronism
sx
* lowered response to stressors
* fatigue
* weight loss + appetite loss
* low BP + hypovolemia
* salt craving
* hyperkalemia
* hypoglycemia
* n/v + vomiting
* depression, irritability
* body hair loss + sex issues + darker skin (hyperpigmentation)
* vitiligo (skin loss color blotches)
Secondary hypocortisolism (adrenal insufficiency)
- low to absent ACTH
- inadeqaute adrenal stimulation
- adrenal atrophy and decrased corticosteroidogenesis
- Common cause —- withdrawal of exogenous administration of glucocorticoids
- Manifestation similar to Addison w/o hyperpigmentation
Hyperfunction of adrenal medulla
- pheochromocytoma (rare, benign tumor in adrenal gland that secretes hormones)
- Sx of cathecholamine excess r/t SNS effects:
- include HTN, palpitations, tachycardia, glucose intolerance, excess sweating and constipation
