Unit 3 Pathophysiology - Chapter 22 Alterations of Hormonal Regulation

Question 1

Endocrine abnormalities

Answer 1

1. decrease in number of receptors
2. receptor insensitivity to hormone
3. present antibodies against specific receptors
4. 2nd messenger defects or postreceptor defects

Question 2

SIADH (Syndrome of inappropriate antidiuretic hormone)

Answer 2

• 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

Question 3

DI (diabetes insipidus)

Answer 3

• 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

Question 4

Dipsogenic polydipsa

Answer 4

• compulsory water drinking
• lowers plasma osmolarity to point that it falls below threshold for ADH secretion

Question 5

Hypopituitarism

Answer 5

• 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

Question 6

Hyperpituitarism

Answer 6

• 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

Question 7

Pituitary adenoma complications?

Answer 7

• 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

Question 8

Hypersecretion of GH

Answer 8

• Adults - acromegaly (too much GH, causing bones, cartilage, body organs and other tissues to increase in size) [pituitary adenoma is common cause]
• Children - gigantism

Question 9

GH deficiency

Answer 9

• Children - growth failure and fastying hypoglycemia
• Adult - fatigue, osteoporosis, and increased mortaility

Question 10

Thyrotoxicosis

Answer 10

• general condition in which TH levels are elevated produced an exaggerated resposne
• heat intolerance
• palpitations
• anxiety
• fatigue
• weight loss
• muscle weakness
• irregular menses

Question 11

Hyperthyroidism

Answer 11

• 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)

Question 12

Graves disease

Answer 12

• 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

Question 13

Toxic multinodular goiter and solitary toxic adenoma

Answer 13

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

Question 14

Thyrotoxic crisis

Answer 14

• Thyroid storm
• Often associated with physiologic stress
• W/o treatment, death occurs quickly

Question 15

Hypothyroidism

Answer 15

• 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

Question 16

Hashimoto or autoimmune thyroiditis

Answer 16

Associated w/ lymphocyte infiltration => antibody activation of natural killer celss => induce apoptosis w/ gradual loss of thyroid function => hypothyroid

Question 17

Subacute thyroiditis

Answer 17

• 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

Question 18

Secondary hypothyroidism

Answer 18

• caused by hypothalamic-pituitary dysfunction in which TRH and TSH are not produced in sufficient amounts

Question 19

Thyroid carcinoma

Answer 19

• cause ionizing radiation (especially childhood)

Question 20

Myxedema

Answer 20

• 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

Question 21

Congenital hypothyrodism

Answer 21

TH deficieny @ birth d/t thyroid agenesis (total lack)
* hypothyrodism, growth failure, intellectual disability d/t absence of thyroxine

Question 22

Papillary and follicular thyroid carcinomas

Answer 22

common thyroid malignancies particulary during childhood d/t ionizing radiation exposure
* thyroid nodules present with normal thyroxine levels

Question 23

Hyperparathyroidism

Answer 23

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

Question 24

Secondary hyperparathyroidism

Answer 24

• 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

Question 25

Tertiary hyperparathyrodism

Answer 25

* excessive secretion of PTH and hypercalcemia that occurs after long-standing hypocalcemia

Question 26

Psuedohypoparathyroidism and familial hypocalciuric hypercalcemia

Answer 26

* 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)

Question 27

Hypoparathyrodism

Answer 27

* low PTH levels (d/t surgery, autoimmunity, genetic mechanisms) * low serum calcium, increased serum phosphate, dereased bone resorption, and EVENTUAL hypocalciuria

Question 28

Calcium and phosphate relationship

Answer 28

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.

Question 29

Type 1 diabetes

Answer 29

* 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

Question 30

Type 2 diabetes mellitus

Answer 30

* 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

Question 31

Insulin resistance and diabetes 2 causes?

Answer 31

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.

Question 32

Other specific types of diabetes mellitus

Answer 32

* 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

Question 33

DKA (Diabetic ketoacidosis)

Answer 33

* 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

Question 34

Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)

Answer 34

* 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

Question 35

euglycemic diabetes-related ketoacidosis (euDKA)

Answer 35

DKA with blood sugar less than 250 mg/dl

Question 36

Hypoglycemia

Answer 36

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

Question 37

Somogyi effect

Answer 37

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

Question 38

Dawn phenomenon

Answer 38

* 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

Question 39

Chronic complications of diabetes mellitus

Answer 39

1. **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]) 2. **Macrovascular disease** (CAD, stroke, peripheral vascular disease [narrowed vessels]) 3. Infection

Question 40

Metabolic changes contibuting to DM complications?

Answer 40

1. oxidative stress 2. shunting of glucose to polyol pathway (30% glucose consumed via this process, glucose reduced to 1) sorbitol then to 2) fructose. 3. 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** 4. 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 5. accumulation of hexosamines (important in glucose uptake, glycogen synthesis, glycolysis and GF synthese) ===> excess l/t **insulin resistance**

Question 41

Microvascular complications r/t elevated sugars

Answer 41

* Alterations to endothelium and basement membrane (extracellular matrix behind endothelium - biochemical + mechanical signaling, tissue integrity, elasticity, and intracellular and intercellular interactions) * thrombosis

Question 42

Diabetic retinopathy

Answer 42

* microvascular change + thrombosis l/t occlusion, retinal ischemia, increased vascular permeability, micro aneurysm formation, hemorrhage, and neovascularization w/ loss of vision

Question 43

Diabetic nephropathy

Answer 43

* 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

Question 44

Diabetic neuropathies

Answer 44

* 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

Question 45

Macrovascular disease and DM

Answer 45

* associated w/ high sugar, high lipids, inflammation, and altered endothelial fx

Question 46

CAD and stroke in diabetes

Answer 46

* 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

Question 47

Peripheral artery disease

Answer 47

* consequence of neuropathy * occluding of large/small arteries resulting in further ischemia, necrosis, and amputation

Question 48

Other uniques risks of diabetic patients

Answer 48

* impaired WBC and suppressed immunity * delayed wound healing

Question 49

Adrenal medulla vs adrenal cortex

Answer 49

Adrenal cortex makes: * aldosterone (mineralcorticoid) * cortisol (glucocorticoid) * estrogen and androgen (sex hormones) Adrenal medulla (center) makes: * epinephrine (adrenaline) and norepinephrine (noradrenaline)

Question 50

Hypofunction of adrenal medulla

Answer 50

no known disorders associated

Question 51

Hypercortisolism (cushing's)

Answer 51

**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**

Question 52

Congenital adrenal hyperplasia

Answer 52

Autosomal recessive disorder * Inadequate synthesis of cortisols --- glucocorticoids (**LOW**) * Increased levels of ACTH => causing adrenal hyperplasia l/t overproduction of mineralocorticoids or androgens

Question 53

Primary hyperaldosteronism

Answer 53

* 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

Question 54

Secondary hyperaldosterone secretion

Answer 54

* 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

Question 55

Adrenal tumors w/ sex hormone regulation

Answer 55

* Adenomas (benign) and carcinomas * can autonomously secrete androgens or estrogens

Question 56

Hypofunction of adrenal cortex

Answer 56

* affect glucocorticoid and/or mineralocorticoid seceretion * caused by ACTH deficiency or by primary deficiency in the GLAND itself

Question 57

Hypocortisolism

Answer 57

* low levels of cortisol * inadeqaute ACTH produciton or by primary cortisol hyposecretion

Question 58

Addison disease

Answer 58

* 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)

Question 59

Secondary hypocortisolism (adrenal insufficiency)

Answer 59

* 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

Question 60

Hyperfunction of adrenal medulla

Answer 60

* 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