Phys Review Flashcards
(83 cards)
1
Q
Hypothalamus secretes
A
TRH (thyrotropin-releasing hormone) CRH (corticotropin-releasing hormone) GnRH GHRH Somatostatin Dopamine
2
Q
Anterior Pituitary secretes
A
TSH FSH (follicle stimulating hormone) LH ACTH MSH (melanocyte stimulating hormone) Growth Hormone Prolactin
3
Q
Posterior pituitary secretes
A
Oxytocin
ADH
4
Q
Thyroid secretes
A
T3, T4 (thyroxine)
Calcitonin
5
Q
Parathyroid secretes
A
PTH
6
Q
pancreas secretes
A
insulin, glucagon
7
Q
adrenal medulla secretes
A
norepi
epi
8
Q
Kidney secretes
A
Renin
1,25 dihydroxycholecalciferol
9
Q
adrenal cortex secretes
A
cortisol, aldosterone, adrenal androgeens
10
Q
testes secrete
A
testosterone
11
Q
ovaries secrete
A
estradiol
progesterone
12
Q
corpus luteum secretes
A
estradiol
progesterone
13
Q
placenta secretes
A
hcg
estriol
progesterone
hpl (human placental lactogen)
14
Q
a positive feedback hormone loop
A
action of estrogen on LH release during midcycle
15
Q
which hormones use nuclear receptors?
A
thyroid and steroid
16
Q
differences between lipid-soluble and water-soluble hormones
A
Lipid soluble:
intracellular receptors, stimulates synthesis of new proteins, synthesized s needed, transported attached to proteins that serve as carriers, long half-life
water-soluble:
receptors on outer surface of membrane, –> production of 2nd messengers that modify action of intracellular proteins, stored in vesicles, sometimes as prohormone, transported dissolved in plasma (free, unbound), short half-life
17
Q
Measurement of Hormone Levels- Plasma analysis:
A
Reflective only of time of sampling
Pulsatile secretion, diurnal variation, cyclic variation, age, sleep entrainment, hormone antagonism, hormone and metabolite interaction, and protein binding can all cause variation in hormone levels
18
Q
Measurement of Hormone Levels- Urine analysis:
A
Restricted to the measurement of catecholamines and steroid hormones
Can reflect an integrated sample
19
Q
primary, secondary, and tertiary conditions with thyroid hormone levels
A
3o- hypothalamic failure– TRH, TSH, and T3/T4 are down
2o- pituitary failure- TRH is up, TSH and T3/ T4 are down
1o- thyroid dysfunction: thyroidities- TRH and TH are up, T3/T3 are down
Grave’s disease- TRH and TSH are down, T3/T4 are up
Tissue unresponsiveness- e.g. mutation in thyroid hormone receptor
20
Q
ADH
A
(posterior pitutitary)
Function is to maintain normal osmolality of body fluids and normal blood volume
Released in response to increased serum osmolality
Works on principle cells of the distal tubule to increase water resorption
Induces contraction of vascular smooth muscle to protect against severe volume depletion
21
Q
Oxytocin
A
Milk letdown
Uterine contraction
22
Q
ADH Action on the Kidney
A
ADH increases expression of aquaporin 2 on the luminal side of principal cells
Water flow from the lumen to the renal interstitium is increased
ADH decreases urine flow and urine osmolality ↑
In the absence of ADH urine flow increases and osmolality ↓
23
Q
Diabetes Insipidus (DI)
A
Characterized by a large volume of urine (diabetes) that is hypotonic, dilute, and tasteless (insipid)
- Neurogenic (hypothalamic or central)- unregulated ADH
- Nephrogenic- unresponsiveness to ADH
- Transient
- Primary polyuria- increased water intake due to pathologic, habitual, or psychiatric syndromes
Distinguish if polyuria is due to an increase in an osmotic agent (i.e. glucose) or due to renal disease
Diagnosis of DI confirmed by dehydration stimulus followed by the inability to concentrate urine
24
Q
Neurogenic vs Nephrogenic diabetes insipidus
A
plasma ADH is normal to high in nephrogenic, low in neurogenic
after water deprivation, plasma ADH goes up in nephrogenic, but not in neurogenic
urine osmolality goes up in neurogenic after ADH administraion but not in nephrogenic
25
things that stimulate growth hormone
```
decreased glucose concentration
decreased free fatty acid concentration
arginine
fasting or starvation
hormones of puberty (etrogen, testosterone)
exercise
stress
stage III and IV sleep
alpha-adrenergic agonists
```
26
things that inhibit growth hormone
```
increased glucose concentration
increased free fatty acid concentration
obesity
senescence
somatostatin
somatomedins
growth hormone
beta-adrenergic agonists
pregnancy
```
27
Summary of GH Actions
```
1. Diabetogenic effect- causes insulin resistance
↓ glucose uptake
↑ blood glucose levels
↑ lipolysis
↑ blood insulin levels
```
2. Increased protein synthesis and organ growth (through the actions of IGF-I)
↑ amino acid uptake
↑ DNA, RNA, protein synthesis
↑ lean body mass and organ size
3. Increased linear growth (through the actions of IGF-I)
Altered cartilage metabolism
28
prolactin induces
dopamine synthesis
29
factors stimulating prolactin
```
pregnancy (estrogen)
breast-feeding
sleep
stress
TRH
dopamine antagonists
```
30
factors inhibiting prolactin
dopamine
bromocriptine (dopamine agonist)
somatostatin
prolactin (negative feedbac)
31
pulsatile vs continuous infusion of GnRH
pulsatile secretion of GnRH prevents downregulation
of its receptors, a constant infusion will cause a decrease
in LH and FSH.
32
Steps in Thyroid Hormone Synthesis
Synthesis of thyroglobulin (TG) and exocytosis to the lumen
Transport of I- into cell- against chemical and electrochemical gradients
Oxidation of I-* - thyroid peroxidase
Organification of iodine into MIT and DIT*; MIT = monoiodothyronine, DIT = diiodothyronine
Coupling reaction*; DIT + DIT = T4, DIT + MIT = T3
Endocytosis of TG
Proteolysis of iodinated thyroglobulin; releases T3 and T4
Deiodination of residual MIT and DIT; recycling of I- and TG
* Inhibited by propylthiouracil (PTU)
33
Transport and Deiodination of Thyroid Hormone
T4 and T3 circulate bound to thyroid-binding globulin (TBG) and to a lesser extent albumin and transthyretin (TTR)
TBG buffers hormone levels in the blood
99.98% of T4 is bound in circulation and 99.5% of T3 is bound
T3 is the more active thyroid hormone as it has a higher affinity for thyroid receptor (10 fold); however the ratio of T4 to T3 is 10:1
Tissues contain deiodinases to convert T4 to T3
People without thyroid function will have T3 upon treatment with T4 only
34
Normal levels of thyroid hormone
Total T4 5-12 μg/dL
| T3 70-190 ng/dl
35
Euthryoid sick syndrome
is characterized by hypothyroidism but the root of the problem does not lie in the thyroid or pituitary. Instead, severe illness is believed to increase the levels of diiodinase D3 which results in the formation of inactive rT3.
36
things that stimulate thyroid hormone
TSH
thyroid-stimulating immunoglobulins
increased TBG (thyroid-binding globulin) levels (e.g. pregnancy)
37
things that inhibit thyroid hormone
I- deficiency
deiodinase deficiency
excessive I- intake (Wolff-Chaikoff effect)
Perchlorate: thiocyanate (inhibit Na+-I- cotransport)
Propylthiouracil (inhibits peroxidase enzyme)
decreased TBG levels (e.g. liver disease)
38
Summary of Thyroid Hormone Actions
nuclear receptor--> transcription of DNA--> translation of mRNA--> synthesis of new proteins that do the following:
growth formation, bone maturation
maturation of CNS
increases Na+-K+ ATPase, O2 consumption, heat production, BMR
increases glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein synthesis and degradation (net catabolic)
increases cardiac output
39
Thyrotoxicosis- Associated with Hyperthyroidism
** TSH will be down compared to normal
1. Grave’s disease- autoimmune thyroid disease (0.5% of population)
2. Factitious thyrotoxicosis- exogenous thyroid hormone with gland atrophy and low thyroglobulin
3. Toxic adenoma “hot nodule”- overproduction of thyroid hormone by the nodule with low TSH and gland atrophy surrounding the nodule
4. Toxic nodular goiter (toxic multinodular goiter)
5. Pituitary overproduction of TSH- rare
6. Granulomatous thyroiditis (* subacute thyroiditis) (viral in etiology) with painful gland
Hyperthyroidism→ euthyroidism→ hypothyroidism→ euthyroidism
7. Subacute lymphocytic thyroiditis (silent thyroiditis) (believed to be autoimmune in etiology) with non-tender gland- transient
Example is postpartum thyroiditis
40
Hypothyroidism
Points of interruption
- Thyroid gland- primary
- Pituitary- secondary
- Hypothalamus- tertiary
- Tissue resistance- rare
Primary
- Hashimoto’s (5-10% of population)- T cell-mediated but antibodies can also be present (α-TPO)
- Radioactive ablation of the thyroid
Secondary
- Pituitary insufficiency
Tertiary
- Hypothalamic disease
41
Adrenal gland zones and hormones
Capsule
Zona Glomerulosa- Aldosterone (controlled by Ang II, K+)
Zona fasciculata cortisol . (controlled by ACTH)
Zona reticularis- androgens (controlled by ACTH)
Medulla- epinephrine (controlled by ANS)
42
aldosterone is regulated by
angiotensin II and potassium levels. The consequence of this control mechanism is that aldosterone and pressure-volume regulation is typically normal in individuals who have hypopituitarism.
43
if 21-alpha-hydroxylase is absent
an excess of androgens will be present with an absence of glucocorticoids and mineralocorticosteroids.
44
the absence of 17-alpha-hydroxylase will cause
an increase in mineralocorticosteroids but an absence of androgens.
45
factors stimulating cortisol secretion
```
decreased blood cortsol levels
sleep-wake transition
stress; hypoglycemia; surgery; trauma
psychiatric disturbances
ADH
alpha adrenergic agonists
beta-adrenergic antagonists
serotonin
```
46
factors inhibiting cortisol secretion
increased blood cortisol levels
opioids
somatostatin
47
actions of glucocorticoids
essential for survival during fasting- increase protein catabolism, decrease protein synthesis, increase lipolysis, decrease glucose utilization by tissues- net result is an increase in glucose synthesis
48
actions of mineralocorticoids
increase Na reabsorption
increase K+ secretion
increase H+ secretion
49
acute release of cortisol -->
metabolic responses to stress ensure sufficient energy to meet increased demand
maintain blood glucose levels necessary for consciousness
also contributes to providing energy for the incipient inflammatory and immune response
but also protects individual from potential damage of unregulated inflammation
50
Response to Chronically Elevated Cortisol
(e.g. Cushing's disease)
--> localized obesity (ab, neck, face)
muscle wasting and weakness, esp. at extremities
usually occurs in context of elevated insulin/ glucagon ratio
high cortisol antagonizes insulin's effect on GLUT-4 in skeletal muscle and adipose tissue --> glucose intolerance --> hyperglycemia and hyperinsulinemia
51
Addison disease
(primary adrenocortical insufficiency)
```
features:
Hypoglycemia
Anorexia, weight loss, nausea, Vomiting
Weakness
Hypotension
Hyperkalemia
Metabolic acidosis
Decreased pubic and axillary hair in females
Hyperpigmentation
```
ACTH levels: increased
treatment: replace glucocorticoids and mineralocorticoids
52
Cushing syndrome
(e.g., primary adrenal hyperplasia)
```
features:
Hyperglycemia
Muscle wasting
Central obesity
Round face, supraclavicular fat, buffalo hump
Osteoporosis
Striae
Virilization and menstrual disorders in females
Hypertension
```
ACTH levels- decreased
treatment: ketoconazole, metyrapone
53
Cushing disease
(excess ACTH)
features- same as cushing syndrome
treatment: surgical removal of ACTH-secreting tumor
54
Conn syndrome
(aldosterone-secreting tumor)
```
features:
Hypertension
Hypokalemia
Metabolic alkalosis
Decreased renin levels
```
treatment: aldosterone antagonist (e.g. spironolactone), surgery
55
21β-hydroxylase Deficiency
features:
Virilization in females
Early acceleration of linear growth
Early appearance of pubic and axillary hair
Symptoms of deficiency of glucocorticoids and mineralocorticoids
ACTH levels: increased
treatment: replace glucocorticoids and mineralocorticoids
56
17α-hydroxylase Deficiency
features:
Lack of pubic and axillary hair in females
Symptoms of deficiency of glucocorticoids
Symptoms of excess mineralocorticoids
ACTH levels: increased
treatment: replace glucocorticoids, aldosterone antagonist (e.g. spironolactone)
57
approach to dx cushing syndrome
1. exclude exogenous steroid use
2. overnight DST OR late-night salivary cortisol OR 24-hour urine free cortisol
positive?
3. Confirm with 1-2 additional studies.
--> if positive, confirmed
58
hormones of endocrine pancreas
insulin (most)
glucagon (some)
somatostatin (5%)
59
actions of insulin
increases glucose uptake into cells and glycogen formation
decreases glycogenolysis and gluconeogenesis
increases protein synthesis and fat deposition
decreases lipolysis
* increases K+ uptake into cells
60
factors stimulating insulin secretion
```
increased glucose, amino acid, and fatty acid/ ketoacid concentrations
glucagon
cortisol
glucose-depending insulinotrpic peptide
potassium
vagal stimulation; Ach
sulonylurea drugs
obesity
```
61
factors inhibiting insulin secretion
```
decreased blood glucose
fasting, exercise
somatostatin
alpha-adrenergic agonists
diazoxide
```
62
Actions of glucagon
increases glycogenolysis, gluconeogenesis, lipolysis, ketoacid formation
63
factors stimulating glucagon secretion
```
fasting
decreased glucose concentration
increased amino acid concentration (esp. arginine)
cholecystokinin (CCK)
beta-adrenergic agonists
Ach
```
64
factors inhibiting glucagon secretion
insulin, somatostatin, increased fatty acid and ketoacid concentration
65
Total calcium levels are maintained within a narrow range in the blood
Hypocalcemic < 8.5 mg/dL (2.1 mM)
| Hypercalcemic > 10.5 mg/dL (2.6 mM)
66
Symptoms of hypocalcemia
twitching, muscle cramps, tingling and numbness
67
Symptoms of hyercalcemia
constipation, polyuria, polydipsia, lethargy, coma, death
68
Changes in albumin levels can
change total calcium levels.
Much of the protein-bound calcium is bound by albumin.
69
Effect of Acid-Base Disturbances on Plasma Protein-binding of Ca2+
acidemia --> increased ionized calcium in the plasma (H+ kicks it off the albumin)
alkalemia --> decreased ionized Ca in the blood (more spots for it to bind to albumin)
70
Overview of Calcium Regulation
3 hormones
- PTH (increases bone resorption)
- 1,25-dihydroxyvitamin D (increases digestive absorption of Ca)
- Calcitonin (decreases bone resoption- TONES the bone)
```
3 organs
- Skeleton
- Kidney
- Intestines
Calcium sensor receptor (CaSR)
7 membrane G-protein coupled receptor
Senses extracellular calcium- ionized calcium
Receptor found on parathyroid cells, parafollicular c-cells, and renal tubular cells
```
71
Four functions PTH
Triggers Ca2+, PO43- resorption from bone
Promotes Ca2+ resorption from the kidney
Promotes PO43- excretion from the kidney
Signals 1-hydroxylation of 25-hydroxycholealciferol in the kidney
72
Functions of 1,25-(OH)2-vitamin D
Bone remodeling (promotes mineralization)
Ca2+ absorption from gut
Renal resorption of Ca2+ and PO43-
73
high levels of extracellular calcium do what to PTH?
suppresses its secretion
74
Bone Remodeling
Osteoprotegerin (OPG) acts as a soluble receptor for RANKL and shuts down resorption by osteoclasts
Loss RANKL ↑ bone density (osteopetrosis)
Loss OPG ↓ bone density (osteoporosis)
75
1,25-dihydroxyvitmain D and bone resorption/ deposition
1,25-dihydroxyvitmain D is necessary for both bone resorption (acts with PTH) and for bone deposition.
76
Severe vitamin D deficiencies can result in
osteomalacia in adults or rickets in children.
77
Synthesis of 1,25-dihydroxyvitamin D
7-dehydrocholesterol + UV light-->
cholecalciferol (also from diet)
via liver to
25-OH cholecalciferol
via kidney to 1,25(OH)2 cholecalciferol (active form) or 24,25 inactive form
78
Degree of Vitamin D Deficiency
0-10 ng/ml- severe
10-20- moderate
20-30- mild
over 30- normal
79
PTH and Calcium Levels in Disease
very high PTH, low Calicum- kidney failure
high PTH and low calcium- vitamin D deficiency
very high calcium low PTH- malignancy
moderately high both- primary hyperparathyroidism
80
Hypercalcemic Disorders
```
Primary Hyperparathyroidism (increased PTH)
Hypercalcemia of Malignancy
Granulomatous Disease
Vitamin D Intoxication
Vitamin A Intoxication
Hyperthryoidism
Thiazide Diuretics
Milk-Alkali Syndrome
Immobilization
Adrenal Insufficiency
Acute Renal Failure
Familial Hypocalciuric Hypercalcemia
Heterozygous inactivating mutation in the CaSR
increased PTH and serum calcium
```
81
Causes of Hypocalcemia
```
Vitamin D Deficiency
Hypoparathyroidism
Pseudohypoparathyroidism
Genetic disorder causing resistance to PTH
Hypomagnesemia
Renal Failure
Liver Failure
Acute Pancreatitis
Hypoproteinemia
```
82
Measurement of 25- OH Vitamin D and PTH are the key tests in the differential diagnosis of hypocalcemia
PTH levels are low in hypoparathryoidism but normal to high in all other causes
Hypomagnesemia impairs PTH secretion and induces PTH resistance in peripheral tissues
Renal disease and liver disease interfere with vitamin D synthesis
Acute pancreatitis causes precipitation of calcium due to the release of lipid products
Hypoproteinemia will reduced total calcium levels but usually do not cause symptoms of hypocalcemia since levels of ionized calcium are typically not altered
83
remembering the zones of the adrenal gland and what they produce
G-F-R glomerulosa, fasciculata, reticularis
Salt-Sugar- Sex
aldosterone- cortisol- androgens
