Pathophysiology Flashcards
(83 cards)
1
Q
Causes of Hypothyrodism
A
atomidine, kelp, lithium
2
Q
Thyroid Hormone Effects
A
- Fetal development (baby makes @ week 11)
- Oxygen consumption & heat production
- CV effects
- Sympathetic effects
- Pulmonary effects
- GI effects
- Skeletal effects
- Lipid & Carbohydrates
- Endocrine Effects
3
Q
Symptoms of Hypothyroidism
A
- fatigue, weakness
- dry skin
- feeling cold
- hair loss
- memory
- constipation
- weight gain w/poor appetite
- menorhagia
4
Q
Signs of Hypothyroidism
A
- dry, coarse skin
- puffy face, hands, feet
- diffuse allopecia
- bradycardia
- peripheral edema
- carpal tunnel syndrome
- serous cavity effusions
- delayed tendon reflex relaxation
5
Q
Symptoms of Hyperthyroidism
A
- fatigue/weakness
- hyperactivity, irritability, dysphoria
- heat intolerance/sweating
- palpitations
- weight loss with increased appetite
- diarrhea
- oligomenorrhea, loss of libido
6
Q
Signs of Hyperthyroidism
A
- tachycardia, atrial fibrillation in elderly
- tremor
- goiter
- warm, moist skin
- muscle weakness, proximal myopathy
- Lid retraction
7
Q
Lab Assessment of TF
A
- TSH
- T4 - total and free
- T3 - total and free
- T3 index
8
Q
Hyperthyroidism
A
- TSH secretion pituitary adenoma
- isolated pituitary resistance to thyroid hormone
9
Q
Hypothyroidism
A
-Central hypothyroidism
10
Q
Euthyroid
A
- systemic illness
- generalized resistance
- assay interference
11
Q
Etiology of Hyperthyroidism
A
-Endogenous Graves disease Toxic multinodular goiter Toxic adenoma Activation mutation of TSH receptor Activation mutation of Gs(alpha) Struma ovarii Thyroiditis Secondary hyperthyroidism -Exogenous
12
Q
Etiology of Primary Hypothyroidism
A
- Thyroiditis
- RIA tx for Graves Disease
- Thyroidectomy
- Excessive Iodine Intake
- Iodine Deficiency
- Inborne errors of TH synthesis
- Drugs (Lithium, Amiodarone, Interferon-alpha)
13
Q
Etiology of Secondary/Tertiary Hypothyroidism
A
- destruction of pituitary gland
- hypothalamic dysfunction
- peripheral resistance to thyroid hormone
14
Q
Classification of Thyroiditis
A
- acute
- subacute
- silent
- Riedel’s thyroiditis
15
Q
Thyroid Enlargement
A
- diffuse nontoxic (simple) goiter
- nontoxic multinodular goiter
- toxic multinodular goiter
- hyperfunctioning solitary nodule
- thyroid neoplasm/cancer
16
Q
What hormones are secreted by the neurohypophysis (posterior pituitary)?
A
Vasopressin & Oxytocin
similar to each other - nonapeptides that differ with 2 amino acids
-ring structure with disulfide linkage
SITE: in magnocellular neurons of supraoptic and paraventricular nuclei of hypothalamus, biosynthesized in diff. cell bodies by macromolecular precursors that are cleaved to yeild active hormone, linking protein (neurophysin) & other peptides
-stored in vesicles at the end of neurosecretory axons in posterior pit. and secreted by Ca-dep. exocytosis
17
Q
Human Vasopressin
A
called arginine vasopressin (AVP)
also called antidiuretic hormone (ADH)
-nonapeptides similar to oxytocin with only 2 amino acid difference
18
Q
Actions of Vasopressin
A
19
Q
Vasopressin Receptor Types
A
V(A1): CV -cause vasoconstriction, in myocardium causes increase in afterload & hypertrophy
V(1B): ant. pit. & median eminence mediate ACTH release
V(2): renal effects, conserves water and concentrates the urine by enhancing the hydro-osmotic flow of water from the luminal fluid through the cells of the collecting tubule of kidney to medullary interstitium
20
Q
Normal Vasopressin Levels
A
-blood conc. fluctuates
max: late night/early morning
min: early afternoon
2.5-8ng/l
inactivation occurs in liver & kidney
7-10% excreted in urine as active hormone
21
Q
Stimuli that lead to release of vasopressin?
A
1) increase in plasma osmolarity
2) decrease in plasma volume
3) activation of carotid/aortic baroreceptors in response to hypotension
4) cholinergic/beta-adrenergic stimuli (+)
atropine & alpha-adrenergic stimulation inhibit (-)
5) aging increases release (60+)
6) drugs can (+), nicotine (+), ethanol (-)
7) H2O deprivation (+), H2O administration (-)
osmotic factors normally control, but override by blood volume if >10% change
8) cortisol (-)
22
Q
Water Porin Channel regulated by Vasopressin?
A
AQP2 in the kidney
-conditions associated with H2O retention like CHF, pregnancy, SIADH are accompanied by increased expression of AQP2
23
Q
Central Diabetes Insipidus
A
“Neurogenic DI”
- failure to conc. urine as a result of decreased secretion of osmoregulated AVP
- uncommon (1 in 25,000)
24
Q
Central Diabetes Insipidus
Signs/Symptoms
A
-polyuria-day and night
-polydipsia (want ice-cold water)
-thirst
kids (enuresis)
-nocturia: chronic tiredness, poor school/work, malaise
25
Central Diabetes Insipidus
| Etiology
-familial or acquired
-inherited AD or Recessive
Majority are acquired
(idiopathic (30% AVP abs), brain tumors, head trauma, granulomas of hypo-pit. area, CNS infection, Cerebral vascular disorders)
26
Pathophysiology of Polyuria
1) insufficient osmoregulated AVP (neruogenic DI)
2) complete/partial renal resistance to antiduretic action of AVP (nephrogenic DI)
3) habitual fluid drinking or primary polydipsia:
psychiatric illness
- abnormal thirst mechanism of idiopathic/specific etiology
27
Diagnosis of Polyuria
- endocrine investigations
| - urine volume > 2.5L in 24hrs
28
Neurogenic Polyuria
water deprivation osmolality increase with dilute urine, give AVP and renal tubules will respond and urine osmolality increase to over 750 mOsm/kg
-low AVP that doesn't increases with hypertonic saline solution
29
Nephrogenic Polyuria
- plasma osmolality in high/normal range
- low urine osmolarity
- fail to respond to water deprivation, urine osmolality remains low and serum osmolality gets very high
- does NOT respond to AVP
- increase AVP with hypertonic saline
30
Primary Polydypsia
-low random plasma osmolality, low urine osmolality
-respond to water deprivation-increase urine osmolality (no defect in AVP secretion/action
-respond to AVP and increase urine osmolality
(if after lots of H2O though, its already saturated)
-increase AVP with hypertonic saline infusion
31
SIADH
"syndrom of inappropriate secretion of ADH"
- plasma vasopressin conc. inappropriately high for plasma osmolality
- with normal water intake, water retention, leading to hyponatremia and hypo-osmolality
32
Causes of SIADH
1) malignant tumors with autonomous AVP release (carcinoma of lung)
2) nonmalignant pulmonary diseases (TB)
3) Central Nervous System (meningitis)
4) Drugs (narcotics)
33
Malignant tumors with AVP
- stored and autonomously released from tumor tissue in amounts that are determined largely by the tumor mass and not by known stimuli
* small cell/oat cell carcinoma of lung 80%*
34
Nonmalignant Pulmonary diseases with AVP
- acquires the capacity to synthesize and release AVP autonomously or reduces left atrial filling with stimulates central AVP release
- hyponatremia is common feature of pulmonary TB and pneumonia
35
Release of AVP from patients neurohypophysis?
-due to neighboring inflammatory, neoplastic, or vascular lesions or drugs and independently of normal stimuli
36
Clinical/Laboratory features of SIADH?
-weight gain
-weakness
-lethargy/mental confusion
-convulsions and coma
Lab: low serum BUN, creatinine, uric acid, albumin
Na < 130mEq/L, osm < 270, urine is hypertonic
urine Na > 20
37
Treatment of SIADH?
1) treat underlying cause/remove drug
2) H2O restriction to no more than 1000mL/24 hrs
3) Drugs that block AVP on distal and convoluted tubules of the kidney, Li has numerous adverse effects, demeclocycline must be used with caution in patients with hepatic dysfunction
4) Very careful infusion of hypertonic saline
5) "Vaptans" 3 AVP receptor subtypes are members of rhodopsin-like G-protein-coupled receptor family
- non-peptide AVP V2 antagonists have been developed to treat hyopnatremia
38
Stimuli for Oxytocin Release
- mechanical distention of the reproductive tract (vagina)
| - suckling of the nipples
39
Actions of Oxytocin
- stimulation of uterine contractions at partutition
| - augmentation of intramammary pressure during suckling
40
Amount of Oxytocin
- pharm doses like in pregnancy (labor) can alter metabolism of water by kidney (1 unit of oxytocin has 0.01 units of ADA) due to biological similarity to ADH
- severe H2O intoxication in women infused with oxytocin at high rates & given hypotonic fluids
41
Other roles of Oxytocin/location of secreting cells
- Magnocellular neurons of hypothalamic paraventricular and supraoptic nuclei, smaller cells scattered around brain secrete also
- learning, anxiety, feeding, pain perception
- modulate social memory, attachment, sexual/material behavior, aggression, human bonding, trust
42
Adrenohypophysiotropic Neurones
- synthesize and secrete peptides or bioamine hormones directly into fenestrated capillaries specialized to receive hormone granules at azonal-capillary terminations in the median eminence (tuber cinereum)
- transported down pit. stalk via a network of fine vessels called the hypophyseal portal venous system, which terminates in capillaries surrounding the anterior pituitary
43
GnRH Stimulates?
- FSH
| - LH
44
GHRH Stimulaties?
-GH
45
TRH Stimulates?
- TSH
| - Prolactin
46
VIP PHI-27 Stimulates?
-Prolactin
47
CRH & ADH
-ACTH
beta-lipotrophin
beta-endorphin
48
Somatostatin Inhibits?
- GH
| - TSH
49
Dopamine Inhibits?
- TSH
| - Prolactin
50
Neurohypophysiotrophic Neurons
- magnocellular (large, long) synthesizing antidiuretic hormone (ADH) and oxytocin
- stored in and secreted from post. pit. directly into systemic blood
51
Negative Feedback
-increase in level of target gland hormone suppresses the secretion of its corresponding pituitary trophic hormone, or the appropriate hypothalamic releasing hormone
52
Positive Feedback
-an increase in the level of the target gland hormone produces an increased secretion of the corresponding trophic or releasing hormone
53
Long-loop Feedback
-target gland hormone regulates secretion at hypothalamic and/or pituitary
54
Short-loop Feedback
-pituitary gland hormone modulates one or more hypothalamic-releasing hormones
55
Ultra-short Feedback
-a hypothalamic hormone influences the secretion of its own hormone secreting neurone (autoaxonal inhibition) or an adjacent neurone (para-axonal inhibition)
56
Neurosecretion
Pulsatility: occures ~every 20min, CRH, ACTH, cortisol, GnRH, LH, FSH, beta-estradiol
Diurnal rhythms: (circadian) time-dependent variation in circulating hormone levels in 24hr period, ACTH peak at 6-8am decrease during day
Sleep-related hormone secretion: GH during day in slow pusatile bursts, 1-2 hr after sleep starts (stage 3-4) get burst of 70%, most in childern
-prolactin also in sleep
57
Hypopituitarism
-partial or complete loss of secretion of one (monotrophic) or more (polytropic) pituitary hormones with clinical manifestations of pituitary failure
58
Monotropic Hypopituitarism
- isolated GH deficiency
| - isolated LH/FSH deficiency; isolated ACTH deficiency (rare) isolated TSH deficiency (rare)
59
Polytropic Hypopituitarism
GH, PRL, LH/FSH, TSH and ACTH deficiency in various combinations
60
Panhypopituitarism
anterior and posterior pituitary failure
61
How much destruction of pituitary affects?
50% no consequences
65-75% moderate effects
90% severe hypopituitarism
compression lesions: expanding pit. tumors gonadotrophic & GH failure, then PRL, TSH, ACTH deficiencies
62
Causes of Hypopituitarism
1) pituitary lesions, which lead to primary hypopituitarism
| 2) hypothalamic lesions, which lead to secondary hypopituitarism
63
Mechanisms of Hypopituitarism
1) Tumors
2) Vascular Infarction
3) Inflammatory Lesions
4) Infiltration
5) Head or post-surgical Trauma
6) "Idiopathic" Hypopituitarism
7) Autoimmune Hypophysitis
8) Empty Sella
64
Hypothalamic Disorders
- various diseases or conditions that involve the hypothalamus may affect the secretion of the hypothalamic hormones which in turn influence the secretion of corresponding pituitary hormones
- include diminution in the secretion of vasopressin with resulting diabetes insipidus
65
Mechanisms of Hypothalamic Disorders
- infiltrative disorders
- mass lesions
- radiation
- infection
- trauma
66
TSH Deficiency
-low T4, low T3
-low/normal TSH
Hypothyroidism: weight gain, no energy, cold intolerance, sluggishness, dry cool skin, delayed relaxation of reflexes
67
ACTH Deficiency
-low cortisol
-low androgens
Hypoadrenalism: hypotension, anorexia, weight loss, aches, pains, loss or axillary hair in wome
68
LH/FSH Deficiency
-low testosterone
-low estradiol/progesterone (female)
Hypogonadism:
Men:Impotence, infertilit
Women: amenorrhea, infertility
69
GH Deficiency
```
-low somatomedin-C (IgF1)
Growth Failure: short stature (children)
insulin sensitivity (adults), premature aging
```
70
PRL Deficiency
```
-low PRL
Failed lactation (adult): alactia
```
71
Static Test
-measure basal (unstimulated) levels
72
Dynadmic Test
-measure stimulated levels following maximal but safe doses of various stimuli
73
Acromegaly: Elevated GH
-loss of nocturnal stage III sleep rise, elevated IgF1
74
Acromegaly: Elevated IFG-I (somatomedin-C)
-increased growth of cartilaginous bones
-increased soft tissue mass and sweat gland hypertrophy
Prognathism, splaying out of teeth, large nose, hands & feet, large nasal sinuses
-thickened skin & subcutaneous tissue, skin tags, excessive sweating
75
Acromegaly: Elevated GH and/or IGF-I
-visceral enlargement
-insulin resistance
Large liver, spleen, kidney
Glucose intolerance or diabetes
76
Acromegaly: Elevated GH and PRL (mixed tumors)
-Galactorrhea & hypogonadism with acromegaly
| Infertility, with acromegaly
77
Elevated PRL in Adult Men
-decreased GnRH
-decreased LH/FSH
-decreased testosterone
decreased libido
impotence
infertility
HYPOGONADISM
78
Elevated PRL in Adult Women
-decreased GnRH
-decreased LH/FSH
-decrease estradiol & progesterone
anovulation
amenorrhea
galactorrhea
infertility
osteopenia
-Increased adrenal androgen secretion = hirsutism
HYPOGONADISM
79
Cushing's: Elevated ACTH
-bilateral adrenal hyperplasia with increased plasma cortisol and adrenal androgen
-loss of diurnal rhythm of ACTH & cortisol
-increased urinary cortisol
increased skin pigmentation due to elevated ACTH
80
Cushing's: Elevated Cortisol
-salt retention insulin resistance, increase fat deposits
-decreased skin collagen
-proximal myopathy
-cerebral effects
HTN, hyperglycemia, diabetes mellitus, obesity (central, buffalo hump, supraclavicular fat pad)
easy bruisability, striae, girdle muscle weakness, depression, emotional lability, psychosis
81
Cushing's: Elevated Adrenal Androgen
- hair growth = hirsutism
- decreased LH/FSH secretion = oligomenorrhea
- increased sebum production = acne, oily skin
- decreased libido = impotence
82
Gonadotroph Adenomas
- most common pituitary macroadenoma
- difficult to recognize because nonfunctioning
- usually recognized when large enough to produce neurological symptoms: visual impairment, but headache, diplopia, CSF rhinorrhea, pituitary apoplexy caused by sudden hemorrhage into the adenoma, and others may occur
83
TSH-secreting adenomas
-rare NOT usual cause of hyperthyroidism, but most cause thyrotoxicosis
-large, 1/3 associated with acromegaly or hyperprolactinemia
-no TSH response to TRH nor TSH suppression to exogenous thyroid hormone
-suppressed by glucocorticoids /somatostatin analog
-85% have elevated alpha subunits in serum
male=female
