ENDOCRINE- Physiology Flashcards
1
Q
How is Insulin synthesized?
A
Preproinsulin → cleavage of “presignal” → proinsulin (stored in secretory granules) → cleavege of proinsulin → exocytosis of insulin and C peptide equally
2
Q
Where is Preproinsulin synthesized?
A
In RER
3
Q
What is increased in Insulinomas?
A
Insulin and C peptide
4
Q
What do exogenous insulins lack?
A
C peptide
5
Q
Where is Insuline released from?
A
pancreatic β cells
6
Q
Which is the mechanism of function of Insulin?
A
Binds insulin receptors, inducing glucose uptake (carrier mediated transport) in insulin dependent tissue and gene transcription
7
Q
What kind of receptors are insulin receptors?
A
Tyrosine kinase activity
8
Q
Which are anabolic effects of insulin?
A
↑ Glucose transport in skeletal muscle and adipose tissue ↑ glycogen synthesis and storage ↑ triglyceride synthesis ↑ Na+ retention (kidneys) ↑ protein synthesis (muscles, proteins) ↑ cellular uptake of K+ and amino acids ↓ glucagon release
9
Q
What is the purpose of insulin?
A
Move glucose into cells
10
Q
Between Insulin and glucose, who crosses placenta?
A
Unlike glucose, insulin does not cross placenta
11
Q
Insulin dependent glucose transporters
A
GLUT-4
12
Q
Where are GLUT-4 found?
A
Adipose tissue
Skeletal muscle
13
Q
Insulin independent transporters
A
GLUT-1
GLUT-5
GLUT- 2
14
Q
Where are GLUT-1 found?
A
RBCs, brain, cornea
15
Q
GLUT-5 is related to this simple ketonic monosaccharide
A
Fructose
16
Q
Places where GLUT-5 is found
A
Spermatocytes, GI tract
17
Q
Characteristic of GLUT-2
A
Bidirectional
18
Q
Where are GLUT-2 found?
A
β islet cells, liver, kidney, small intestine
19
Q
During starvation what does the brain uses for metabolism?
A
Ketone bodies
20
Q
For the metabolism of RBCs what is used? can they use Ketone bodies?
A
RBCs always utilize glucose
They can’t use ketone bodies
21
Q
Why RBC only utilize glucose?
A
Because they lack mitochondriafor aerobic metabolism
22
Q
Who is the major regulator of Insulin release?
A
Glucose
23
Q
Who cause ↑ insulin?
A
GH
β2 agonist
24
Q
How does GH causes ↑ insulin release?
A
Causes insulin resistance → ↑ insulin release
25
How is Insulin exocytosis stimulated?
Glucose enters β cells → ↑ATP generated from glucose metabolism closes K+ channels and depolarizes β cell membrane →opens voltage gated Ca2+ channels, resulting in Ca2+ influx and stimualting insulin exocytosis
26
Made by α cells of pancreas
Glucagon
27
Functions of Glucagon
Catabolic effects of glucagon:
Glycogenolysis, gluconeogenesis
Lipolysis and cetone production
28
What stimulates the secretion of Glucagon?
Hypoglycemia
29
Who inhibits Glucagon?
Insulin
Hyperglicemia
Somatostatin
30
Which is the function of CRH?
↑ ACTH, MSH, β endorphin
31
Common condition of ↓ CRH
In chronic exogenous steroid use
32
Effect of Dopamine
↓ prolactin
33
Drugs that can cause galactorrhea? How do they act?
Antipsychotics- Dopamine antagonists
34
Who are increased with GnRH secretion?
FSH, LH
35
Who regulates GnRH?
Prolactin
36
Which situation can suppress Hipothalamic- pituitary axis?
Tonic GnRH
37
What leads to puberty, fertility
Pulsatile GnRH
38
Effect of Prolactin
↓ GnRH
39
Clinical effects of Pituitary prolactinoma
Amenorrhea
| Osteoporosis
40
Function of Somatostatin
↓ GH, TSH
41
Which is the clinical use fro Somatostain?
Analogs used to treat acromegaly
42
Function of TRH
↑ TSH, prolactin
43
Where is Prolactin secreted?
Mainly by anterior pituitary
44
Function of Prolactin
Stimulates milk production in breast
| Inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH synthesis and release
45
Which clinical manifestation is associated with excessive amounts of prolactin?
↓ Libido
46
Who regulates Prolactin secretion?
Prolactin from anterior pituitary is tonically inhibited by dopamine from hypothalamus
47
Prolactin itself stimulates hypothalamus secretion of...
Dopamine, so at the end prolactin in turn inhibits its own secretion by ↑ Dopamine synthesis and secretion from hypothalamus
48
Which Dopamine product stimulates prolactin secretion?
TRH
49
Which drugs could be use to inhibit prolactin secretion?
Dopamine agonists
50
Dopamine agonist
Bromocriptine
51
Which is the clinicla use for Bromocriptine?
Treatment for Prolactinoma
52
Which drugs stimulate prolactin secretion
Dopamine antagonists
| Estrogens
53
Who are Dopamine antagonists?
Antipsychotics
54
Estrogen related situation that stimulate prolactin secretion
OCPs
| Pregnancy
55
Growth hormone
Somatotropin
56
Where is Somatotropin secreted?
Mainly by anterior pituitary
57
Function of Somatotropin
Stimulates linear growth and muscle mass
| ↑ insulin resistance
58
How does Somatotropin stimulates linear growth and muscle mass?
Through IGF-1/ somatomedin secretion
59
How is GH consider?
Diabetogenic
60
Who regulates the secretion of Somatotropin?
Released in pulses in response to GHRH
61
When is GH secretion increased?
During exercise and sleep
62
Who inhibits GH secretion?
By Glucose and somatostatin
63
Which are the possible outcomes of excess secretion of GH (eg. pitiuitary adenomas)?
Acromegaly (adults)
| Gigantism (children)
64
Where is Antidiuretic hormone synthesized?
Hypothalamus (supraoptic nuclei)
65
Where is Antidiuretic hormone released?
Posterior pituitary
66
Antidiuretic hormone function
Regulates serum osmolarity and blood pressure
67
Which receptors regulate serum osmolarity?
V2 receptors
68
Which receptors regulate blood pressure stimulated by Antidiuretic hormone?
V1 receptors
69
Which is the primary function of ADH?
Serum osmolarity regulation
70
What is the effect of ADH?
↓ serum osmolarity
| ↑ urine osmolarity
71
How does ADH regulates Serum osmolarity?
Via regulation of aquaporin channel transcription in principal cells of renal collecting duct
72
When are ADH levels decreased?
↓ in central diabetes insipidus
73
In these situations ADH levels are normal or increased
In nephrogenic Diabetes insipidus
| Primary polydipsia
74
What causes Nephrogenic Diabetes insipidus?
By mutation in V2 receptor
75
ADH analog
Desmopressin
76
Treatment for Central Diabetes Insipidus
Desmopressin (ADH analog)
77
Who are the regulators of ADH?
Osmoreceptors in hypothalamus (1º)
| Hypovolemia (2º)
78
Who stimulates Cholesterol desmolase in the conversion from Cholesterol to Pregenolone?
ACTH
79
Which drug inhibits Cholesterol desmolase in the conversion from Cholesterol to Pregenolone?
Ketoconazole
80
The conversion from Corticosterone to Aldosterone, which enzime carries this process? and who positively stimulates it?
```
Aldosterone synthase (enzyme)
Angiotensin II
```
81
If 17 α hydroxylase is deficient, which are the results?
↑ Mineralocorticoids
↓ Cortisol
↓ Sex hormones
82
Labs found in 17 α hydroxylase deficiency
Hypertension
Hypovolemia
↓ Dihydrotestosterone
83
Presentation of 17 α hydroxylase deficiency
XY: pseudo hermaphroditism (ambiguous genitalia, undescend testis)
XX: lack secondary sexual development
84
Name enzyme deficiency in Adrenal gland
17 α hydroxylase
21- hydroxylase
11 β hydroxylase
85
If 21- hydroxylase is deficient, which are the effects?
↓ Mineralocorticoids
↓ Cortisol
↑ Sex hormones
86
Which are the expected labs for 21- hydroxylase deficiency?
Hyperkalemia
Hypotension
↑ Renin activity
↑ 17-hydroxy- progesterone
87
Which is the most common enzyme deficiency of Adrenal gland?
21- hydroxylase deficiency
88
How is 21- hydroxylase deficiency presented during infancy?
Salt wasting
89
How is 21- hydroxylase deficiency presented in childhood?
Precocious puberty
90
How else is 21- hydroxylase deficiency presented?
XX: virilization
91
Which is the effect of 11β hydroxylase?
↓ Aldosterone
↑ 11 deoxycorticosterone
↓ Cortisol
↑ Sex hormones
92
What is affected in 11β hydroxylase deficiency?
Hypertension (low renin)
93
Presentation of 11β hydroxylase deficiency
XX: virilization
94
Which is the common characteristic of all congenital adrenal enzyme deficiencies?
By an enlargement of both adrenal glands
95
Why there is enlargement of adrenal glands in congenital adrenal enzyme deficiencies?
Due to ↑ ACTH stimulation
96
Why there is ↑ ACTH stimulation in congenital adrenal enzyme deficiencies?
Due to ↓ Cortisol in every adrenal enzyme deficiencies
97
Source of Cortisol
Adrenal zona fasciculata
98
Function of Cortisol
```
BIG FIB
↑ Blood pressure
↑ Insulin resistance
↑ Gluconeogenesis, lypolisis, proteolysis
↓ Fibroblast activity
↓ Inflamatory and Immune responses
↓ Bone formation
```
99
How does Cortisol increases blood pressure?
Upregulated α1 receptors on arterioles → ↑ sensitivity to norepinephrine and epinephrine
100
How is Cortisol consider related to insulin?
Insulin resitance (diabetogenic)
101
Which metabolic pathways are affected with Cortisol?
↑ Gluconeogenesis, lypolisis, proteolysis
102
Why Cortisol causes striae?
↓ Fibroblast activity
103
How does Cortisol causes ↓ Inflamatory and Immune responses?
Inhibits production of leukotrienes and prostaglandins
Inhibits leukocyte adhesion → Neutrophilia
Blocks histamine release from mast cells
Reduces eosinophils
Blocks IL-2 production
104
How does Cortisol causes Decreased bone formation?
↓ Osteoblast activity
105
How is cortisol trnasported in blood?
Bound to corticoesteroid binding globulin
106
Why do you need to be very careful when administering cortisol?
Can cause reactivation of TB and candidiasis
107
Why Cortisol can cause reactivation of TB and candidiasis?
Blocked IL-2 production
108
Who stimulates ACTH release?
CRH (hypothalamus)
109
Which is the effect of excess cortisol?
↓ CRH, ACTH, and cortisol secretion
110
What does chronic stress induce in Adrenal Cortex?
Prolonged Cortisol secretion
111
Source of PTH
Chief cells of parathyroid
112
Which is PTH function?
↑ bone resorption of Ca2+ and PO4 3-
↑ Kidney reabsorption of Ca2+ in distal convoluted tubule
↓ reabsorption of PO4 3- in proximal convoluted tubule
↑ 1, 25 (OH)2 D3 production by stimulating kidney 1α hydroxylase
113
Alternative name for 1, 25 (OH)2 D3
Calcitriol
114
In resume what does PTH does?
↑ serum Ca2+
↓ serum (PO4 3-)
↑ urine (PO4 3-)
115
Who is stimulated by PTH in order to produce Calcitriol?
Kidney 1α hydroxylase
116
Where are Ca2+ and PO4 3- reabsorption points in kidneys?
In distal convoluted tubule
117
Which other effect does PTH has related to Macrophages and NK?
↑ production of macrophage colony stimulating factor and RANK-L (receptor of activator of NF-κB ligand)
118
What is the effect of RANK-L on osteoblasts?
RANK-L binds RANK on osteoblasts → Osteoclast stimulation and ↑ Ca2+
119
When do we find PTH related peptide (PTHrP)?
Commonly increased in malignancy (eg paraneoplastic syndrome)
120
What is the function of PTHrP?
Functions like PTH
121
What stimulates regulate PTH?
↓ serum Ca2+ → ↑ PTH secretion
↓ serum Mg2+ → ↑ PTH secretion
↓↓ serum Mg2+ → ↓ PTH secretion
122
Common causes of ↓ Mg2+
Diarrhea
Aminoglycosides
Diuretics
Alcohol abuse
123
Which is the recombinant human PTH?
1-84
124
Which calcium positiveli stimulated four parathyroid gland?
Low ionized calcium
125
Name the three forms of Plasma Ca2+
Ionized
Bound to albumin
Bound to anions
126
Which kind of Ca2+ can be presented in three forms?
Plasma Ca2+
127
Which percentage of Ca2+ is ionized?
45%
128
How much Ca2+ is bound to albumin?
40%
129
Ca2+ bount to anions
15%
130
What stimulate Increases the affinity of Albumin to bind Ca2+?
↑ in pH
131
Why increased pH increases the affinity of albumin to bind Ca2+?
Albumin is negative charged
132
Clinical manifestations of hypocalcemia
Cramps, pain, paresthesias, caspopedal spasm
133
Alternative name for Vitamin D
Cholecalciferol
134
How is D3 obtain?
From sun exposure in skin
135
How is D2 obtain?
Ingested from plants
136
Which Vitamin D is converted in the liver?
Both D2 and D3
137
What is the product of Vitamin D2 and D3 after processed in liver?
25-OH
138
Which organ metabolizes Vitamin D2 and D3 to become 25-OH?
Liver
139
Which is the active form of 25-OH?
1, 25 (OH)2
140
Where is 25-OH activated in order to become 1, 25 (OH)2?
Kidneys
141
Which is the function of Cholecalciferol?
↑ absorption of dietary Ca2+ and PO4 3-
| ↑ bone resorption → ↑ Ca2+ and PO4 3-
142
Which stimulates cause ↑ 1,25- (OH)2 production?
↑ PTH
↓ PO4 3-
↓ Ca2+
143
Who inhibits 1,25 (OH)2 production?
1,25 (OH)2 feedback inhibits its own production
144
Which disease is caused by Vitamin D deficiency in kids?
Rickets in kids
145
Disease caused by Vitamin D deficiency in adults
Osteomalacia
146
Which are the causes of Vitamin deficiency?
Malabsorption
↓ sunlight
poor diet
chronic kidney failure
147
Inactive form of Vitamin D
24,25 (OH)2 D3
148
What does PTH leads to?
↑ Ca2+ reabsorption and ↓ PO4 3- reabsorption in kidneys
149
What does 1,25 (OH)2 leads to?
Absorption of both Ca2+ and PO4 3- in the gut
150
Source of Calcitonin
Parafolicular cells (C cells) of thyroid
151
Function of Calcitonin
↓ bone resorption of Ca2+
152
Who regulates Calcitonin?
↑ serum Ca2+ causes calcitonin secretion
153
Who opposes PTH actions?
Calcitonin
154
Is calcitonin important in normal Ca2+ homeostasis?
No
155
From which endocrine hormones is cAMP the signaling pathway?
```
FLAT ChAMP
FSH
LH
ACTH
TSH
CRH
hCG
ADH (V2 receptor)
MSH
PTH
calcitonin, GHRH, glucagon
```
156
cGMP is the signaling pathway from these endocrine hormones
ANP, NO (EDRF)
157
IP3 is the signaling pathway from these endocrine hormones
```
GOAT HAG
GnRH
Oxytocin
ADH (V1 receptor)
TRH
Histamine (H1 receptor)
Angiotensin II
Gastrin
```
158
Who have Steroid receptor?
```
VETTT CAP
Vitamin D
Estrogen
Testosterone
T3/T4
Cortisol
Aldosterone
Progesterone
```
159
These endocrine hormones act in Intrinsic tyrosine kinase
```
Insulin
IGF-1
FGF
PDGF
EGF
```
160
Which pathway is related to intrinsic tyrosine kinase?
MAP kinase pathway
161
Receptor associated tyrosine kinase
Prolactin, Immunomodulators, GH
| acidophiles, cytokines
162
Who are immunomodulators?
cytokines, IL-2, IL-6, IL-8, IFN
163
Which pathway is related to receptor associated tyrosune kinase?
JAK/STAT pathway
164
How are steroid hormones consider?
Lipophilic
165
If steroid hormones are lipophili, how do they circulate in the body?
Must circulate bound to specific binding globulins, which increase their solubility
166
What happens if ↑ sex hormone binding globulin in men?
Lowers free testosterone→ fynecomastia
167
What would be the result If ↓ sex hormone binding globulin in women?
Raises free testosterone → hirsutism
168
Which situation increase sex hormone binding globulin?
OCPs
| pregnancy
169
Which estrogen levels remain unchanged in OCPs and pregnancy?
Free estrogen levels remain unchanged, the ones that change are the ones bind to sex hormone binding globulin
170
What are the thyroid hormones?
Iodine containing hormones that control the bodys metabolic rate
171
Where are Thyroid hormones formed?
Follicles of thyroid
172
Where is most of T3 formed?
In target tissues
173
Function of Thyroid hormones
```
Bone growth
CNS maturation
↑ β1 receptors in heart
↑ basal metabolic
↑ glycigenolysis, gluconeogenesis, lipolysis
```
174
For Bone growth which hormones have synergism?
GH and Thyroid hormones
175
Which is the effect of ↑ β1 receptors in heart caused by thyroid hormones?
↑ Cardiac output, HR, Stroke volume, contractility
176
Which channels are activated in order to increase basal Metabolic rate stimulated by Thyroid hormones?
Via ↑ Na+/K+-ATPase activity
177
What is the effect of increase basal Metabolic rate Via ↑ Na+/K+-ATPase activity stimulated by Thyroid hormones?
↑ O2 consumption, Respiratory rate, body temperature
178
How are thyroid hormones regulated?
TRH (hypothalamus) stimulates TSH (pituitary), which stimulates follicular cells
179
How does the negative feedback for Thyroid hormones work?
Negative feedback by free T3, T4 to anterior pituitary ↓ sensitivity to TRH
180
Who stimulate follicular cells?
Thyroid stimulating immunoglobulins (TSIs)
| TSH
181
What is the Wolf Chaikoff effect?
Excess iodine temporarily inhibits thyroid peroxidase → ↓ iodine organification → ↓T3/T4 production
182
Excess iodine temporarily inhibits thyroid peroxidase → ↓ iodine organification → ↓T3/T4 production
Wolf Chaikoff effect
183
T3 functions
```
4 B's
Brain maturation
Bone growth
β adrenergic effects
Basal metabolic rate increased
```
184
Which is the effect of Thyroxine binding globulin?
Binds most T3/T4 in blood
185
Which Thyroid hormone is active?
Only free hormone
186
When is Thyroxine binding globulin (TBG) decreased?
In hepatic failure
187
During these situations Thyroxine binding globulin (TBG) increased
Pregnancy
| OCP use
188
Which hormone increases Thyroxine binding globulin (TBG)?
Estrogen
189
Who is the major thyroid product?
T4
190
Where is T4 converted to T3?
Peripheral tissue
191
Which enzyme manage the conversion from T4 to T3?
5' deiodinase
192
Which Thyroid hormone binds receptors with greater affinity?
T3
193
Which is the function of Peroxidase?
Is enzyme responsible for oxidation and organification of iodide as well as coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT)
194
Who inhibits both peroxidase and 5' deiodinase?
Propylthiouracil
195
Which is the effect of Propylthiouracil?
Inhibits both peroxidase and 5' deiodinase
196
Which is the effect of Methimazole?
Inhibits peroxidase only
197
Who inhibits peroxidase only?
Methimazole
198
Anions that inhibit Follicular cell production of Thyroid hormones?
Perchlorate
Pertechnetate
thiocyanate
199
Who are Antithyroid drugs?
Propylthiouracil
| Methimazole
