Endocrine Pathophys Flashcards
1
Q
SIADH
dorwart chalmers formula
A
serum osmolality = (1.86(Na)) + (Glucose/18) + (BUN/2.8) + 9
2
Q
SIADH
smithline and gardner formula
A
serum osmolality = 2(Na) + glucose/18 + BUN/2.8
3
Q
SIADH
normal serum osmolality ranges
A
275 mOsm/Kg to 295 mOsm/kg
4
Q
SIADH
what to do after checking serum osmolality?
A
UA (for urine osmolality)
5
Q
SIADH
normal response to water deprivation
A
- H2O deprivation
- increased plasma osmolarity
- osmoreceptors stimulated to increase ADH secretion from post pit
- increased H2O permability of cells increase H2O reabsorption
- increased urine osmolarity and volume
- decreased plasma osmolarity toward normal
6
Q
SIADH
Effect of ADH
A
- increase H2O permeability in late distal tubule collecting duct
- increase activity of Na K 2Cl transporter (increase Na intake, H2O follows)
7
Q
SIADH
volume change of what? causes shift of ADH levels?
A
- > 10% volume change
- shock would trigger ADH secretion to maintain vol
8
Q
SIADH
what can happen if you too rapidly correct hyponatremia
A
Locked In Syndrome
9
Q
SIADH
overall characterize SIADH
A
- ADH is secreted independently of osmoreceptors
- Produces Hyperosmotic urine, Hypoosmotic Plasma, and Abnormally High levels of ADH
10
Q
Male Hypogonadism
role of sertoli cells
A
Sertoli cells are a type of sustentacular “nurse” cell found in human testes which contribute to the process of spermatogenesis
11
Q
Male Hypogonadism
Leydig Cells
A
produce testosterone in the presence of LH
12
Q
Male Hypogonadism
key players in male HPG axis
A
- Hypothalamus produces GnRH
- Ant Pituitary produces FSH and LH (neg feedback to the hypothalamus)
- Testes produce testosterone and inhibin (neg feedback to the ant pit)
- testosterone can neg feedback of the hypothalamus
- LH stimulates Leydig cells to make testosterone
- FSH stimulates Sertoli cells to produce ABP and inhibin
- Sertoli cells to support sperm production
13
Q
Male Hypogonadism
which are gonadotropins?
A
- FSH and LH are glycoproteins secreted by gonadotrophs of the APG
- secretion is regulated by GnRH of the hypothalamus
14
Q
Hyperaldosteronism
overall what does RAAS regulate?
A
BP (slowly)
15
Q
Hyperaldosteronism
RAAS pathway
A
- angiotensinogen (liver)
- renin (kidney)- converts-
- angiotensin I
- antiongensin converting enzyme (ACE) - (lungs/kidney) - converts-
- angiotensin II
- systemic effects
16
Q
Hyperaldosteronism
RAAS direct renal mechanism
A
- increase of mean arterial pressure causes increased filtration rate in the tubules
- this means the kidney cannot reabsorb filtrate fast enough –> more fluid leaves the body in the urine –> blood volume decreases –> lower BP
17
Q
Hyperaldosteronism
RAAS indirect renal mechanism
A
reduced mean arterial pressure & Na+ concentration decreases kidney perfusion leading to…
* cells of macula densa stimulate renin production from the juxtaglomerular cells after sensing change in osmolarity
* ACE stimulates secretion of aldosterone from the glomerulosa cells of adrenal gland which increases Na+ reabsorption & increases blood osmolality
* Angiotensin II increases Na+ reabsorption, ADH secretion, thirst, and vasoconstricts arterioles to increase peripheral resistance
18
Q
Hyperaldosteronism
two components of fetal adrenal gland? what do they do?
A
- definitive: principal site of glucocorticoid and mineralcorticoid synthesis
- fetal: androgenic precursors which the placenta converts to various types of estrogens
19
Q
Hyperaldosteronism
Mature adrenal gland histology
A
- cortex (zona glumerulosa, fasciculata, reticularis)
- medulla
20
Q
Hyperaldosteronism
function of zona glomerulosa
A
- produces mineralcorticoids (aldosterone)
- sodium reabsorption in the kidney, electrolyte balance, intravascular volume, blood pressure
21
Q
Hyperaldosteronism
function of zona fasciculata
A
- produces glucocorticoids (cortisol)
- uniquitous physiologic regulators, influences variety of body functions
22
Q
Hyperaldosteronism
function of zona reticularis
A
- produces sex steroids (androgens)
- too much can cause secondary sex characteristics in women
23
Q
Hyperaldosteronism
what regulates aldosterone?
A
- renin-angiotensin system
- hyperkalemia
24
Q
Endocrine System Overview
endocrine system is collective term for?
A
all endocrine glands and hormone secreting cells distributed throughout the body
25
# Endocrine System Overview
differentiate endocrine glands/cells versus neuroendocrine/neurosecretory cells
* endocrine: lacks a duct, secretes their hormone into surrounding tissue/fluid and it is taken up by the blood and carried throughout the body
* neuro: neurons that produce and release their secretions/hormones in response to signals from the nervous system
26
# Endocrine System Overview
what are hormones
| 3 things
* chemical messenger secreted into bloodstream
* produces a response only in certain target cells that possess a receptor
* control and coordinate body's metabolism, energy level, reproduction, growth/development, response to injury/stress/mood
27
# Endocrine System Overview
Hypothalamus location
region of forebrain located below the thalamus and posterior to optic chiasma
28
# Endocrine System Overview
hypothalamus connects to what? via what?
connects to pituitary gland via neural and circulatory connections
29
# Endocrine System Overview
major functions of hypothalamus
* hormone regulation and secretion from pit gland
* autonomic regulation
* thermoregulation
* food/water/sleep/circadian rhythm
* memory
* emotional behavoirs
30
# Endocrine System Overview
Pituitary Gland (hypophysis) location
* seated in the SELLA TURCICA of the sphenoid bone below hypothalamus
* attached to the hypothalamus by the infundibulum
31
# Endocrine System Overview
names of two pituitary lobes
* anterior pituitary (adenohypophysis)
* posterior pituitary (neurohypophysis)
32
# Endocrine System Overview
pituitary gland job
secretes severeal hormones and regulates the acitivity of other hormone secreting glands
33
# Endocrine System Overview
nerve fiber connections between hypothalamus and pituitary
**Hypothalamohypophysial Tract**
* synthesized in the hypothalamus, stored in the post pit
* neurons in the paraventricular and supraoptic nuclei have direct projections that end in the post pit
* **paraventricular nuclei**: produce oxytocin (stimulate uterine contractions + releases during lactation)
* **supraoptic nuclei**: primarily produce ADH/vasopressin (vasoconstrictor that increases absorption of Na+/H2O from renal tubules)
34
# Endocrine System Overview
bloodstream connection between the hypothalamus + post pit
**Hypothalamohypophysial Portal System**
* formed from branches off the internal carotid arteries
* arteries travel through median eminence (pituitary stalk) into the capillaries that surround cells within anterior pituitary
* **Releasing hormones**: corticotropin-releasing hormone (CRH), thyrotropin releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), growth hormone-releasing hormone (GHRH)
* **Release Inhibiting hormones**: somatostain, dopamine
35
# Endocrine System Overview
Anterior pituitary hormones
synthesizes and secretes 6 hormones
* Non-tropic Hormone: prolactin (PRL), growth hormone (GH)
* Tropic Hormones: Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH)
36
# Endocrine System Overview
which part of pituitary gland actually produces its own hormones?
anterior
37
# Endocrine System Overview
differentiate tropic and non-tropic hormones
* Non-tropic: directly stimulates target cells to induce effects
* Tropic: pituitary hormone who target organ is another endocrine gland
38
# Endocrine System Overview
which two hormones does the post pit store? how do they travel from hypothalamus to post pit?
* stores: ADH, OT
* travel: down the hypothalamohypophyseal tract via infundibulum
39
# Endocrine System Overview
control of pituitary secretion
* timing and the amoung of pituitary secretion is regulated by the hypothalamus, higher brain structures, feeback from target organs
40
# Endocrine System Overview
Anterior Pituitary control of secretion
* releasing hormones: stimulate secretion by pituitary cells
* inhibiting hormones: suppress secretion from pituitary cells
41
# Endocrine System Overview
Posterior pituitary control of hormone secretion
* controlled by neuroendocrine reflexes
* ADH: released when there is increase in blood plasma osmolality or decrease in blood volume
* Oxytocin (OT): released during labor + after nipple stimulation
42
# Endocrine System Overview
release of oxytocin breastfeeding
1. suckling stimulates nerves in nipple to signal hypothalamus
2. hypothalamus stimulates the posterior pituitary to release oxytocin & anterior pituitary to release prolactin
3. oxytocin simtulates lobules in the breast to release milk, prolactin stimulates milk production
| pos feedback
43
# Endocrine System Overview
oxytocin in birth
1. head of baby pushes against cervix
2. nerve impulses to the brain
3. pituitary releases oxytocin
4. oxytocin stimulates uterine contractions
44
# Endocrine System Overview
what is pitocin
* synthetic substance that mimics oxytocin
* given to induce labor
45
# Endocrine System Overview
ADH overview
* aka vasopressin
* wants blood osmolality 275-295 mOsm/L
* increased osmolality (dehydration) is detected by the hypothalamuc neurons (osmoreceptors) and release ADH from post pit
* ADH acts on distal tubule to reabsorb water (lowers urine volume and stimulates thirst)
46
# Pituitary Adenomas
types of secretory adenomas
* lactotroph (increased prolactin -> hyperprolactinemia)
* somatotroph (increased GH --> acromegaly/gigantism)
* corticotroph (increased cortisol --> Cushing's)
* thyrotroph (increased TSH --> secondary hyperthyroidism)
47
# Pituitary Adenomas
what is seen w/ CN III palsy
* ptosis (inactivation of levator palpebrae)
* mydriasis (decreased tone of constrictor pupillae muscle)
* down & out (unopposed left superior oblique and lateral rectus muscles)
48
# Gigantism & Acromegaly
Growth Hormone is also known as?
somatotropin
49
# Gigantism & Acromegaly
growth hormone is produced by?
anterior pituitary
50
# Gigantism & Acromegaly
what signals the release of GH?
growth hormone releasing hormone (GHRH)
51
# Gigantism & Acromegaly
major effects of growth hormone
* stimulates the liver to produce **insulin like growth factors** (IGFs- 4types)
* tells adipose cells to break down stored fat (**lipolysis**)
* Liver to break down glycogen into glucose (**glycogenolysis**)
* liver to produce glucose (**gluconeogenesis**)
52
# Gigantism & Acromegaly
impact of GH on insulin?
increased insulin resistance in the tissues --> not moving glucose into cells --> increased blood glucose levels
53
# Gigantism & Acromegaly
Describe insulin-like growth factor 1
* aka somatomedin C
* produced by liver with inc. GH
* binds IGF-1 receptors to: **promote cellular metabolism, muscle growth, long bone growth**
54
# Gigantism & Acromegaly
describe oral glucose tolerance test/GH suppression test
* helps determine if the pituitary is releasing too much GH
* drink w/ 75g glucose
* measure serume GH before and after 2 hrs
* >1 ng/mL is abnormal (with an increase in blood glucose, GH should be suppressed)
55
# Gigantism & Acromegaly
which is in kids? which is in adults?
* kids: gigantism (growth plates open during sx onset)
* adults: acromegaly (growth plates already closed)
56
# Dwarfism
define short stature
* height vertex below 2SD or in 3rd percentile for given age/sex
* adult height < 4 ft 10 in
57
# Dwarfism
which type is achondroplasia
* disproportionate dwarfism
* average sized torso, short limbs, large head
58
# Dwarfism
which presentation is associated with GH deficiency
proportionate dwarfism
59
# Thyroid Gland
anatomy of thyroid gland
* largest endocrine gland
* located below larynx and wraps around anterior/lateral sides of trachea
* two large lobes connected by narrow anterior isthmus
60
# Thyroid Gland
anatomy of thyroid follicles
* filled w/ colloid
* lined by follicular cells
* secrete thyroxine (T4) and triiodothyronine (T3)
61
# Thyroid Gland
anatomy of parafollicular cells
* aka C cells
* located between follicular cells
* secrete calcitonin and decrease blood Ca+ levels
62
# Thyroid Gland
describe T3/T4 homeostasis loop
* Homeostasis: normal T3 and T4 concentrations, normal body temp
* disturbances: decreased T3/T4
* hypothalamus releases TRH --> adenohypophysis releases TSH --> thyroid follicles release T3 and T4
63
# Thyroid Gland
differentiate T3 and T4
* T3: primary active thyroid hormone
* T4: circulates blood, converted as needed to T3
64
# Thyroid Gland
other name for TSH?
thyrotropin
65
# Thyroid Gland
where are thyroid hormones stored?
* stored in the follicular lumen
* bound to protein (thyroglobulin- TG)
* bound hormones can't diffuse into cells, unbound/free hormone can bind thyroid receptors and exert effects
66
# Thyroid Gland
what inhibits the conversion of T4 to T3?
* aging
* fasting/calorie restriction, obesity
* inflammation
* sleep deprivation
* stress
* acute/chronic conditions of liver, kidney, intestines
* alcohol
* meds: amiodarone, propranolol, propylthiouracil
67
# Thyroid Gland
factors which can increase conversion of T4 to T3
* zinc
* selenium
* vitamin A
* vitamin E
68
# Thyroid Gland
4 functions of thyroid hormones
* increased metabolism
* growth & development
* interrelated actions w/ catecholamines
* regulates pituitary hormone synthesis
69
# Hypothyroidism
levothyroxine
| dose, when to take, avoid
* 1.6 mcg/kg PO QD
* 30 min before eating or bedtime
* check TSH level every 4-6 wks until reach goal of 1-2
* avoid: calcium, iron supplements w/in 4 hrs
70
# Thyroiditis
generally what is it
inflamamtion of the thyroid gland
71
# Thyroiditis
2 types of thyroiditis
* Hashimoto's (autoimmine, crhonic lymphocytic thyroiditis)
* painful subacute thyroiditis
72
# Hashimoto's Thyroiditis
pathophys
* trigger leads to autoimmune destruction causing progressive depletion of thyroid epithelial cells
* thyroid cell destruction is mediated by CD8+ cytotoxic cells + local production of cytokines
* antibodies made to thyroglobulin (Tg) and/or thyroid peroxidase (TPO)
* lymphocytic infiltration and fibrosis of thyroid cells --> distruption of follicles and release of stored thyroid hormones
73
# Thyroid
describe thyroid uptake scans + potential results
* evaluates thyroid function + pathology
* uses radioactive iodine
* hyperthyroidism: very black, increased uptake in both lobes
* toxic goiters: uneven uptake
* toxic adenomas: increased uptake in one area
* thyroiditis: decreased or absent uptake
74
# Thyroid Nodules
high risk US features of thyroid nodules
* solid
* hypoechoic (indicates solid mass of dense tissue)
* microcalcifications
* irregular margins
* extrathyroidal extension
75
# Hyperthyroidism
describe production of thyroid hormones
* tetraiodothyronine (T4, thyroxine) --> 2 tyrosine + 4 iodine
* Triiodothyronine (T3, most metabolically active) --> 2 tyrosine + 3 iodine
* convert T4 to T3 PRN
76
# Hyperthyroidism
review HPT axis
* hypothalamus: TRH which stimulates....
* pituitary: TSH which stimulates....
* thyroid: T4 + T3
* T4 + T3: inhibit hypothalamus (TRH) + pituitary (TSH)
77
# Hyperthyroidism
causes
| 3
* increased synthesis of thyroid hormones (primary)
* excessive passive release of thyroid hormones (primary)
* extrathyroidal source (pituitary adenoma, secondary)
78
# Hyperthyroidism
which patients CANNOT get the RAIU + thyroid scan? what do you do instead?
* cannot be used in pregnancy or while lactating
* use US to detect diffuse enlargement, solitary/multiple nodules, and increased vascularity of the gland
79
# Hyperthyroidism
which tissues do these work on?
* Beta-1 blockers
* Beta-2 blockers
* Beta-3 blockers
* beta 1: heart/kidney
* beta 2: lung, muscles
* beta 3: adipose tissue
80
# Hyperthyroidism
differentiate selective and non-selective?
* selective: only block beta-1 receptors (**atenolol**, metoprolol, carvedilol, nebivolol)
* non-selective: block both beta 1 and beta 2 receptors (nadolol, **propranolol**, pindolol, sotalol)
81
# Hyperthyroidism
contraindications of BBs
* bradycardia, hypotension
* uncontrolled HF
* 2nd or 3rd degree AV blocks
82
# Hyperthyroidism
purpose of BBs
* block beta receptors which prevents the catecholamines norephinephrine and epinephrine from binding and activating them which decreases sympathetic nervous system response
83
# Hyperthyroidism
MOA anti-thyroid meds
* inhibit oxidation and organic binding of thyroid iodine by inhibiting thyroid peroxidase
* inhibits extrathyroidal conversion of T4 to T3
84
# Hyperthyroidism
antithyroid meds- baseline labs required and why?
* baseline CBC
* liver function
* due to risk of agranulocytosis
85
# Hyperthyroidism
what is agranulocytosis
acute, drug induced blood disorder characterized by severe reduction in number of WBCs in circulation
86
# Hyperthyroidism
when to use methimazole? when to use propylthiouracil?
* methimazole: preferred except during first trimester of pregnancy due to birth defectsm can be used during thyroid storm
* propylthiouracil: used in 1st trimester of pregnancy or if TTC or thyroid storm; BBW for severe liver damage
87
# Hyperthyroidism
describe use of radioactive iodine (I-131) ablation
* contraindicated in pregnancy or lactation
* most pts will become hypothryoid within 2-6 mo
* PO capsule which progressively destroys thyroid cells
88
# Multiple Endocrine Neoplasia
what can you not give a diabetic pt who has MEN?
GLP-1 inhibitors (increases risk for development of medullary thyroid cancer)
89
# Hypoglycemia
what happens to glucagon response after 5 yrs of DM?
pts lose glucagon response (glucagon increases glucose in the blood when it senses low sugars)
**pts do not MAKE glucagon, they can still be responsive to it**
90
# Hypoglycemia
how can this occur in pt w/out DM?
* requires full workup to see what is happening
* potential causes: eating less/exercising more, alcohol consumption, meds, hypermetabolic states (sepsis, burns), tumors (insulinomas)
91
# Hypoglycemia
Glucose homeostasis
* serum glucose levels should be 71-99 mg/dL fasting
* homeostasis coordinated between insulin, glucagon, and SNS
92
# Hypoglycemia
body response to insulin less than 80? less than 68? less than 66?
* 80: insulin secretion decreases
* 68: glucagon, norephinephrine, and epinephrine secreted
* < 66: growth hormone and cortisol secreted (increases lipolysis, ketogenesis, and gluconeogenesis)
93
# Hypoglycemia
role of glucagon in response to hypoglycemia? norephinephrine?
* **glucagon**: mobilizes glycogen from liver to increase blood glucose by ~36 mg/dL in 15 min
* **norephinephrine**: acts systematically to cause adrenergic symptoms of hypoglycemia including tachycardia/diaphoresis
94
# Hypoglycemia
role of epinephrine in response to hypoglycemia?
* stimulates glycogenolysis and gluconeogenesis in the liver
* decreases insulin secretion
* increases glucagon secretion from pancreatic islet cells
* increases lipolysis in adipose tissue (provides glycerol for gluconeogenesis)
* decreases glucose uptake by muscle cells
95
# Hypoglycemia
differentiate glycogenolysis, gluconeogenesis, lipolysis
* **Glycogenolysis**: process by which glycogen breaks down into glucose PRN for energy when fasting
* **Gluconeogenesis**: process that allows the body to form glucose from non-hexose precursors, particularly glycerol, lactate, pyruvate, propionate, and glucogenic amino acids
* **Lipolysis**: process through which triacylglycerols (TAGs) break down via hydrolysis into their constituent molecules (glycerol and FFA)
96
# Hypoglycemia
meds causing hypoglycemia
* **insulin**
* meglitinides (repaglinide, nateglinide)
* sulfonylureas (glipizdie, glimepiride, glyburide)
* BBs
* ethanol
* quinolones
* salicylates (ASA)
* MAO-I
97
# Hypoglycemia
MOA of insulin
increase glucose uptake by skeletal muscle and adipose tissue
98
# Hypoglycemia
when does coma/death occur?
< 40 mg/dL
99
# Hypoglycemia
Whipple Triad
hypoglycemia in non-diabetic pts
* confirmed glucose concentration < 70 mg/dL
* signs/sx associated w/ hypoglycemia
* resolution of sx after correcting hypoglycemia
100
# Type 1 DM
endocrine fucntion of pancreas
* islet of langerhans cells secrete hormones and hormone like messangers
* Insulin: secreted by beta cells in response to increased glucose
* Glucagon: secreted by alpha cells in response to decreased glucose
101
# Type 1 DM
exocrine function of pancreas
digestive enzymes secreted by acinar cells
102
# Diabetes Mellitus
disorder is characterized by what two things?
* poor insulin production
* resistance to insulin
103
# Type 1 DM
simpilifed pathophys
* T cell immune mediated destruction of insulin producing pancreatic islet cells leading to absence of insulin production
| AUTOIMMUNE
104
# Type 1 DM
which two antibodies are most commonly present?
* glutamic acid decarboxylase antibodies (GAD- adults)
* insulin autoantibodies (IAA, children)
105
# Type 1 DM
describe the three stages
* **Stage 1**: **asx**, characterized by **normal** fasting glucose/glucose tolerance, but presence of **>2 pancreatic autoantibodies**
* **Stage 2**: **asx**, characterized by **pancreatic autoantibodies (multiple)**; **dysglycemia** (impaired fasting glucose/glucose tolerance, abnormal HbA1c)
* **Stage 3**: evidence of diabetes defined as **hyperglycemia w/ clinical sx**
106
# Type 1 DM
how do 1/3 of pediatric patients present intially?
DKA
107
# Type 1 DM
in children how can polyuria present?
* enuresis (can't hold pee --> wetting the bed)
* nocturia (urination at night)
108
# Type 1 DM
interpret results of fasting plasma glucose (FPG)
* no calories for > 8 hrs
* > 126 mg/dL at least 2 times = DM
* 100-125 would be prediabetic (T2 DM)
109
# Type 1 DM
describe dawn phenomenon
* in the early AM, hormones (GH, cortisol, catecholamines) cause the liver to release large amounts of glucose into blood stream
* in pts w/ DM, the body does not produce enough insulin which causes high blood sugar in the morning
* if blood sugar is normal to high at 2-3am, it is this phenomenon. Avoid eating carbs late at night.
110
# Type 1 DM
describe somogyi effect
* blood sugar level drops too low in the early morning hours, hormones (GH, cortisol, catecholamines) are released to reverse low blood surgar levels
* in DM - pts who takes insulin and do not eat a bedtime snack will experience drops in sugar during night and the body will respond by releasing hormones
* low blood sugar in early AM = this!
111
# Type 1 DM
components of DexCom for management
* continuous glucose monitoring system
* measures glucose continuously in the interstitial fluid for 7-14d
* data can be transmitted to Dr. offices prior to appts
* alarms can be set for levels
112
# Type 1 DM
which meds are rapid acting insulin? Basal insulin?
* rapid: glulisine, lispro, aspart
* basal: glargine, detemir
113
# Hyperglycemic Crises
compare and contrast HHS & DKA
* hyperglycemia (more severe in HHS)
* dehydration
* hyperosmolality (more severe in HHS)
* electrolyte abnormalities
* ketoacidosis (only in DKA)
114
# Hyperglycemic Crises
normal physioloigc response to increased serum glucose
* high sugar detected by pancreatic beta cells to release insulin
* insulin will decrease glucagon secretion from pancreatic alpha cells; stop gluconeogenesis/glycogenolysis in the liver; increase glucose uptake by muscle/adipose cells
115
# Hyperglycemic Crises
pathophys
* results from problems relating to insulin: decreased glucose utilization by periph tissues; increased glycogenolyssi/gluconeogenesis by the liver
* this leads to increased plasma osmolality (high solute- glucose) which draws water out of the cells and dilutes the Na+ concentration in the interstitial space
116
# Hyperglycemic Crises
when would glucosuria occur?
serum glucose levels are >180 mg/dL
117
# Hyperglycemic Crises
what are the effects of glucosuria?
* increase in osmotic pressure of urine leading to polyuria
* loss of water --> dehydration --> hyperosmolality --> K+ shifts out of cells --> increased extracellular potassium, decreased intracellular potassium
* impaired renal function, AKI
118
# Diabetes Mellitus Type 2
effects of chronic hyperglycemia
* high serum glucose level >180 mg/dL exceeds renal threshold causing glucosuria, polyuria (increase in urine osmolality), polydipsia (dehydration)
* intracellular glucose deficiency causing polyphagia
* chronic complications: CV disease, neuropathy, nephropathy, retinopathy
119
# Adrenal Insufficiency
anatomy of adrenal glands
* adrenal medulla (inner portion, responds to sympathetic stimulation by secreting catecholamines)
* adrenal cortex (thicker outer portion, synthesizes 25 steroid hormones- corticosteroids)
* 3 layers of adrenal cortex: zona glomerulosa (outer), zona fasciculata (middle), zona reticularis (inner)
120
# Adrenal Insufficiency
three types of corticosteroids
mineralocorticoids, glucocorticoids, sex steroids
121
# Adrenal Insufficiency
describe mineralocorticoids
* secreted by **zona glomerulosa**
* control electrolyte balance
* act on kidney
* primary is **aldosterone**
122
# Adrenal Insufficiency
describe glucocorticoids
* secreted by **zona fasciculata**
* stimulate fat/protein catabolism
* gluconeogenesis (synthesis of glucose from non-carb sources) in the liver
* release FA and glucose into blood, help body adapt to stress
* main glucocorticoid is **cortisol**
123
# Adrenal Insufficiency
describe sex steroids
* secreted by **zona reticularis**
* androgens and estrogens
* main androgen is **dehydroepiandrosterone** (DHEA)
124
# Adrenal Insufficiency
describe aldosterone
* operates in RAAS
* secreted directly in response to hyperkalemia and via RAAS in response to low blood volume/pressure
* works to move Na+ into blood (H2O follows) thus increasing blood volume/pressure
125
# Adrenal Insufficiency
primary, secondary, and tertiary causes of adrenal insufficiency
* primary: dysfunction or destruction of adrenal cortex
* secondary: conditions that cause deficiency in pituitary adrenocorticotrophic hormoen (ACTH) secretion
* tertiary: conditions that cause deficiecny in the hypothalamic secretion of corticotropin-releasing hormone (CRH)
126
# Adrenal Insufficiency
causes of primary insufficiency
**Addison's**
* autoimmune (most common): adrenal cortex gradually destroyed --> loss of mineralocorticoids, glucocorticoids, and adrenal androgen hormone production
* could also be infection (TB), hemorrhage (rupture of adrenal cortex blood vessles due to increased BP causing tissue ischemia), metastatic cancers
127
# Adrenal Insufficiency
secondary causes of insufficiency
* hypopituitarism (decreased ACTH)
* pituitary tumors/surgery
128
# Adrenal Insufficiency
causes of tertiary insufficiency
* prolonged high dose glucocorticoid use suppresses HPA axis
* treating Cushing's
129
# Adrenal Insufficiency
describe HPA axis
* hypothalamus secretes CRH --> release of ACTH from anterior pituitary
* ACTH release is pulsatile via circadian rhythm (increases in early AM, peaks at 8:30am, decreased in evening)
* ATCH stimulates zona fasciculata (cortisol) and zona reticularis (androgens) in the adrenals
* the zona glomerulosa is regulated by the renin-angiotensin system & K+ level
130
# Cushing Syndrome
which hormone is out of wack?
cortisol
131
# Cushing Syndrome
differentiate primary, secondary
* **primary**: increased production of glucocorticoids by adrenal glands (tumors)
* **secondary**: Cushing's disease (subtype of cushing syndrome); increased pituitary ACTH production leading to adrenal gland hyperplasmia (commonly see pituitary adenoma)
* **secondary**: ectopic ACTH syndrome; increased ACTH production outisde pituitary and adrenal glands (e.g. paraneoplastic syndromes like SCLC)
132
# Cushing Syndrome
describe exogenous cushing syndrome
* most common form of hypercortisolism
* medical use of glucocorticoids
* expgenous cortisol causes neg feedback at level of hypothalamus and ant pit (reduced CRH and ACTH)
* due to: long term use of glucocortioids (fasciculata atrophy, cortisol no longer produced by body) or abrupt discontinuation of glucocorticoids (body can't produce it anymore --> adrenal crisis)
133
# Cushing Syndrome
differentiate ACTH dependent and ACTH independent Cushing's
* Dependent: body makes too much ACTH which subsequently increases production of cortisol
* Independent: adrenal glands produce cortisol without stimulation from ACTH
134
# Diabetes Insipidus
types
| 4
1. central diabetes insipidus (CDI)
2. nephrogenic diabetes insipidus (NDI)
3. gestational diabetes insipidus
4. dipsogenic diabetes insipidus (primary polydipsia)
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# Diabetes Insipidus
pathophys of central (neurogenic)
decreased production by hypothalamus or decreased release of ADH from posterior pituitary causing polyuria
136
# Diabetes Insipidus
pathophys of nephrogenic
decrease in urinary concentrating ability as a result of resistance to the action of ADH
137
# Diabetes Insipidus
causes and pathophys of nephrogenic DI
| 3
* **Hereditary**- X-linked inheritance, mutation in vasopressin V2 receptor, mutation in aquaporin-2 gene
* **Drug Induced**: chronic lithium use (causes dysfunction of aquaporin-2 water channel)
* **Acute/Chronic Kidney Diseases**: reduction in maxiumum renal concentrating ability due to fewer nephrons/damage to tubules
138
# Diabetes Insipidus
use of desmopressin in central DI
* synthetic form of ADH/vasopressin
* first line med for central
* give at minimum dose to prevent nocturia, take at bedtime
* risk for hyponatremia- nausea, vomiting, HA, lethargy, seizure, coma
139
# Diabetes Insipidus
use of thiazide diuretics (hydrochlorothiazide) for nephrogenic DI
* increases proximal tubule sodium and water reabsorption and less water delivered to ADH sensitive collecting tubules
140
# Diabetes Insipidus
use of indomethacin (NSAID) for nephrogenic DI
increase renal concentration of urine by inhibiting renal synthesis of prostaglandins (ADH antagonists)
141
# Parathyroid Disorders
use of calcium in the body
* all intake is dietary
* strong bones/teeth
* smooth muscle contraction
* cofactor for enzymatic rxns
* regulation of clotting
142
# Parathyroid Disorders
storage of calcium in the body
* 45% free ionized form
* 40% bound to albumin/protein
* 15% complexed w/ anions
143
# Parathyroid Disorders
components of parathyroid glands
* 4 total glands located posterior to thyroid gland
* Chief cells synthesize, secrete, and store PTH
144
# Parathyroid Disorders
general job of PTH? via what cells?
regulates calcium levels in the blood through calcium sensing receptors within chief cells
145
# Parathyroid Disorders
3 functions of PTH (patho, more specific)
* increases calcium and phosphate releases from bones via osteoclast formation
* increases calcium reabsorption and phosphate excretion in the distal tubule of the kidney
* increases synthesis of 1,25 dihydroxyvitamin D (active vit D) which will increase calcium absorption from the gastrointestinal tract
146
# Parathyroid Disorders
relationship between calcium &
* phosphate
* vitamin D
* magnesium
* phosphate: inverse
* vitamin D: direct
* magnesium: direct
| "commit to memory" :-)
147
# Parathyroid Disorders
what stimulates secretion of PTH?
* decreased serum calcium
* low levels of 1, 25 dihydroxyvitamin D (active vit D- **calcitriol**)
* as levels of phosphorus increase, levels of free calcium in the blood decrease because phosphorus binds to calcium
* low magnesium
148
# Parathyroid Disorders
what is calcitonin produced by? functions?
* produced by parafollicular cels (c cells) of thyroid gland
* secretion stimulated by increased serum calcium
* function: inhibits activity of osteoclasts (prevent calcium release from bone) and decreases calcium reabsorption in the kidneys
calcitonin = too much calcium = tell the bones to keep their Ca2+ and tells the kidneys to get rid of Ca2+
149
# Parathyroid Disorders
differentiate primary, secondary, tertiary diseases
* **Primary**: elevated PTH independent of Ca2+ levels
* **Secondary**: elevated PTH due to chronic hypocalcemia
* **Tertiary**: long-standing secondary hyperthyroidism or autonomous functioning of parathyroid glands
150
# Parathyroid Disorders
causes of primary hyperparathyroidism
* most common cause of hyperparathyroidism
* 95% occur sporadically (benign adenomas 85%, hyperlasia 15%, carcinoma < 1%)
* 5% due to familial genetic mutations (MEN 1/4)
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# Parathyroid Disorders
causes of secondary hyperparathyroidism
* chronic renal failure
* bypass surgery
* malabsorption (celiac/crohn's)
* severe vitamin D deficiency
152
# Parathyroid Disorders
what is Tc99 sestamibi scan?
radioactive substance absorbed by hyperactive parathyroid gland
153
# Parathyroid Disorders
when to use total serum Ca2+ for evaluation of serum calcium? when to use ionized Ca2+ for evaluation of serum calcium?
* Total: normal albumin
* Ionized: low albumin
154
# Parathyroid Disorders
causes of hypoparathyroidism
* autoimmune destruction
* thyroiditis
* tissue resistance to PTH (pseudohypoparathyroidism)
* radiation/damage to thyroid or parathyroid
* heavy metal overload (iron overload (hemochromocytosis) or copper (Wilson's disease))
