Endocrine - Adrenal Glands Flashcards
1
Q
Define
Stress Response
What is it? Why do we have it? What can cause it?
A
The normal physical response to events that make you feel threatened or upset your balance
Evolved to help us survive
Almost anything can start it (Traffic, party planning, exams)
2
Q
Stress Response
Unproductive
A
Not enough or too much stress
3
Q
Stress Response
Optimal Production
A
Width varies based upon stress tolerance
equilibrium between having stress and lack of stress
Some stress is good
4
Q
General
General Adaptation Syndrome
A
Nervous and hormonal responses result in a state of intese readiness with fuel mobilized for use
Nonspecific regardless of type of stressor = Stress response
5
Q
Stress response to cold
A
Shivering and skin vasoconstriction
Specific response characteristic of stressor type
6
Q
Stress response is coordinated by…
A
The hypothalamus
7
Q
Short-term stress response:
Symptoms
A
- Increased Heart Rate
- Increased BP
- Liver converts glycogen to glucose and releases glucose to blood
- Bronchdilation
- Changes in blood flow patterns leading to decreased digestive system actovoty and reduced urine output
- Increased metabolic rate
8
Q
Long-term Stress Response from Mineralcorticoids:
Symptoms
A
- Retention of Na and H2O by kidneys
- Increased blood volume and BP
9
Q
Long-term Stress Response from Glucocorticoids:
A
- Proteins and fats converted to glucose or broken down for energy
- Increased blood glucose
- Suppression of Immune System
10
Q
What are the layers of the adrenal gland?
A
Zona glomerulosa
Zona fasciculata
Zona reticularis
Adrenal Medulla
11
Q
What hormones are made and released from the adrenal Zona glomerulosa? What does it do?
A
Mineralcorticoids (ex: Aldosterone)
Regulate mineral balance
12
Q
What hormones are made and released from the adrenal Zona fasciculata? What does it do?
A
Glucocorticoids
Regulate glucose metabolism
Cortisol, Corticosterone, Cortisone
13
Q
What hormones are made and released from the adrenal Zona reticularis? What does it do?
A
Androgens
Stimulate masculinization
Dehydroepiandrosterone
14
Q
What hormones are made and released from the Adrenal medulla? What does it do?
A
Stress hormones
Stimulate sympathetic ANS
Epi, NE
15
Q
What is the pathway of epinephrine synthesis?
A
Tyrosine → DOPA → Dopamine → NE → Epi
PNMT produced by cortisol converts NE to Epi
16
Q
The Adrenal Cortex is -% of the Adrenal Gland.
A
80-90%
17
Q
The Adrenal Medulla is -% of the Adrenal Gland.
A
10-20%
18
Q
The Adrenal Cortex synthesizes _ hormones.
A
Steroids
19
Q
The Adrenal Medulla synthesizes _ hormones.
A
Amines
20
Q
The embryonic origin of the Adrenal Cortex is…
A
Mesoderm
21
Q
The embryonic origin of the Adrenal Medulla is…
A
Neuroectoderm
Neural Tissue
22
Q
What innervation does the Adrenal Cortex have?
A
Nearly none
23
Q
What innervation does the Adrenal Medulla have?
A
SNS
Causes release of catecholamines
24
Q
What are the characteristics of cells in the Adrenal Cortex?
A
Lipid Droplets
25
What are the characteristics of cells in the Adrenal Medulla?
Amine Granules
26
Is the Adrenal Cortex essential for life?
Yes
27
Is the Adrenal Medulla essential for life?
No
28
# Define
Mesoderm
The germ layer that forms many muscles, the circulatory and excretory systems, and the dermis, skeleton, and other supportive and connective tissue
29
# Differential Distribution of Enzymes
Synthesis of Mineralcorticoids in the Zona granulosa:
Cholesterol → ACTH stimulates cholesterol desmolase → Pregneonlone → Progesterone → 11-Deoxycorticosterone → Corticosterone → Ang II stimulates aldosterone synthase → Aldosterone
| 17 - α Hydroxylase is absenth in the ZG
30
# Differential Distribution of Enzymes
Synthesis of Androgens:
* Cholesterol → ACTH stimulation → Pregnenolone or Progesterone
* Pregnenolone → 17α hydroxylase converts to 17-hydroxypregeneolone → Dehyroepiandrosterone → can be converted to Androstenedione
* Progesterone → 17α hydroxylase converts to 17-hydroxyprogesterone → Androstenedione
31
# Differential Distribution of Enzymes
Synthesis of Glucocorticoids:
* Cholesterol → ACTH stimulation → Pregnenolone or Progesterone
* Pregnenolone → 17α hydroxylase converts to 17-hydroxypregeneolone → 17-hydroxyprogesterone → 11-Deoxycortisol → Cortisol
32
Factors that stimulate (↑) ACTH Secretion
↓ blood cortisol levels
Sleep-wake transition
Stress; hypoglycemia; surgery; trauma
Psychiatric Disturbances
## Footnote
Also: ADH, α-Adrenergic agonists, β-Adrenergic agonists, Serotonin
33
Factors that inhibit (↓) ACTH Secretion
↑Blood cortisol levels
Opioids
Somatostatin
34
What is the function of ACTH?
* Stimulates all steps in synthesis of cortisol, adrenal androgens, and slightly aldosertone (only cortisol feeds back)
* Stimulates cell hyperplasia (vis IGF-1 in ZF and ZR)
* ↑ACTH = hyperpigmentation
35
# Cortisol Secretion
Pulsatile
Alternating bursts of modest secretion seperated by silent periods of little to no secretion
* Amount of cortisol secreted with each burst does not vary
* Frequency of secretory bursts vary
* Reminiscent of summation
| One burst adds onto the previous burst
36
# Cortisol Secretion
Diurnal Rhythm
ACTH and cortisol peak prior to awakening
Lowest levels are reached just prior to sleep
| Need low cortisol to sleep
37
_ determines the diurnal rhythm of cortisol secretion.
Suprachiasmatic Nucleus
38
What alters the setting of the diurnal rhythm of cortisol secretion?
Lack of bright natural light during day of exposure to artifical loight at night
Chronic glucocorticoids (blunts morning peak)
39
Stress stimulation of Cortisol Secretion
↑Stress - ↑ cortisol
Enhances the activity of the CRH-ACTH system
↑plasma cortisol in proportion to the intensity of the stressful stimuli
| Can override the stabilizing negative feedback control
40
How does stress override the stabilizing negative feedback control?
Continuous stress produces continuous cortisol → high cortisol wont inhibit ACTH → stress overrides feedback
41
How is cortisol transported through the blood?
Predominantly bound to proteins (Corticosteroid-binding globulin, CBG, Transcortin) [75%]
15-20% bound to albumin
5% Unbound
42
_ is the predominant site of sterpid inactivation
Liver
43
How does the liver inactive steroids?
Inactivates and conjugates with glucuronide or sulfate to ↑ solubility and facilitate excretion by kidney
44
The half-life of cortisol is...
70 minutes
45
Mechanism of Action of steroids
1. Adrenal steroids diffuse into target cell and interact w/ intracellular receptors
2. Receptor is bound to other proteins, including heat shock proteins (HSP)
3. Hormone binds to receptor-HSP
4. HSP released
5. Activated receptor now has high affinity for steroid-response element of the DNA, binds
6. Once bound, hormone-receptor complex acts as a transcription factor to regulate gene expression (mRNA)
7. ↑protein synthesis
| Once bound to the receptor the steroid can enter the nucleus
46
What are the terapeutically important consequences of steroid hormone activation?
Lag period (30 min - several hours) to produce their effects
Effects can last hours or days due to the slow turnover of enzymes and proteins
| Time is required to synthesize a new protein
47
What are the 4 functions of Cortisol?
1. Stimulate gluconeogenesis in response to low blood glucose
2. ↑protein and lipid breakdown (provides GNEO substrates)
3. Anti-inflammatory effects
4. Suppress immune response
| Liver makes glucose in response to cortisol
48
# Effects of Cortisol on Metabolism
What is the effect of ↑blood glucose caused by ↑cortisol?
* Mobilizes proteins from muscle
* Mobilizes fats froma dipose tissue
* ↑GNEO by stimulating GNEO enzymes and ↑responsiveness to glucagon and Epi
* Inhibition of insulin-stimulated glucose uptake by muscle and adipose
* Blocks the suppressive effects of insulin on hepatic glucose output
## Footnote
Provides glucose for brain, essential for survival during prolonged fasting
49
# Effects of Cortisol on Metabolism
What is the short-term effect of cortisol?
It is permissive for the lipolytic action of CATs
| Breakdown of lipids
50
# Effects of Cortisol on Metabolism
What is the long-term effect of cortisol?
Cortisol → ↑ GNEO → ↑hyperglycemia → ↑insulin secretion → ↑lipogenesis (fat synthesis)
51
# Effects of Cortisol on Metabolism
What is the effect of ↑Body fat caused by ↑cortisol?
Stimulates appetitie (CNS effect)
Stimulates FFA uptake in certain adipose tissue depots
Overall: excess cortisol results in the accumulation of fat, but the obesity has a peculiar distribution, favoring the face and trunk
52
# Effects of Cortisol on Metabolism
What is the effect of ↑Protein Breakdown caused by ↑cortisol?
↓ amino acid utilization everywhere other than the liver
Overall: ↓ protein synthesis
53
# Effects of Cortisol on Metabolism
What are the general effects of cortisol on the body?
Cortisol is a catabolic , anti-anabolic, and diabetogenic hormone
Breaks down, prevents produciton, ↑blood glucose
54
# Cortisol affects diverse tissues and organs
What effect does excessive cortisol have on muscles? How?
| What does it do? what causes it?
Muscle breakdown
Excess cortisol can result in muscle weakness and pain
excessive proteolysis (muscle wasting)
Hypokalemia - hyperpolarizes muscle cell membrane
55
# Cortisol affects diverse tissues and organs
Cushing's Syndrome
| Define. What classifies it?
Selective accumulation of abdominal fat and loss of musculature in extremities
56
# Cortisol affects diverse tissues and organs
What effect does excessive cortisol have on bone? How?
↑bone breakdown
↑ bone resorption → ↓intestinal Ca2+ absorption and renal Ca2+ reabsorption → ↑PTH
Inhibit osteoblast functions
57
# Cortisol affects diverse tissues and organs
What is the relationship between excessive cortisol and the vascular system?
Required for maintenance of normal BP
Permissive effect on arterioles to the constrictive action of adrenergic and angiotensin stimulation
58
# Cortisol affects diverse tissues and organs: Cortisol and Vasculature
Cushings Syndrome (Too much cortisol)
| What effect does it have on the vasculature and BP?
Hypertension
59
# Cortisol affects diverse tissues and organs: Cortisol and Vasculature
Absence of Cortisol (too little)
| What effect does it have on the vasculature and BP?
Hypotension and death
60
# Cortisol affects diverse tissues and organs
What is the effect of cortisol on the kidney?
Inhibits the secretion and action of ADH (↑water diuresis
| ↑GFR by ↑RBF
61
# Cortisol affects diverse tissues and organs
What is the effect on cortisol on the CNS?
Cortisol receptors are concentratedin the hippocampus (memory and learning) and reticular activating substance (state of arousal)
Cortisol affects perceptual and emotuonal functioning
62
# Cortisol affects diverse tissues and organs
What is the effect of **excess** cortisol on the CNS?
Insomnia and elevated/depressed mood
63
# Cortisol affects diverse tissues and organs
What is the effect of cortisol on a fetus?
Cortisol facilitates in utero maturation of the CNS, retina, skin, GI tract, and lungs
↑synthesis of surfactant (↓ alveolar surface tension); permits breathing immediately after birth
facilitates maturation of enzymes of intestinal mucosa from fetal to adult pattern → permits new borns to digest disaccarides in milk
64
# Cortisol affects diverse tissues and organs
What are the **beneficial** effects of cortisol on inflammatory and immune responses?
↓Inflammatory reactions that may be life-threatening (severe asthma attack)
Prevents rejection of a transplanted organ
65
# Cortisol affects diverse tissues and organs
What are the **adverse** effects of cortisol on inflammatory and immune responses?
Vulnerability to serious infection, diabetes,osteoporosis, psychiatric disorders
66
What causes ACTH dependent hypersecretion of cortisol (Cushing's Syndrome)?
Pituitary Microadenoma (Cushing's Disease; 80%)
ACTH Secreting ectopic tumor (20%)
CRH secreting ectopic tumor (rare)
67
What causes ACTH independent hypersecretion of cortisol (Cushing's Syndrome)?
Adrenal tumor
Latrogenic - treatment of rheymatoid arthritis, allergies, prevention of transplant rejection
68
Typical Findings in Cushing's Syndrome
| What are the symptoms?
Truncal obesity
Moon face
Hypertension
Skin atrophy
Diabetes
Gonadal dysfunction
Muscle weakness
Hirsuitism, Acne
Mood
Osteoporosis
69
What is the normal feedback loop from the hypothalamus to the adrenal gland?
Hypothalamus secerets ACTH → stimulates adrenal gland → releases cortisol → Negatively feeds back to inhibit hypothalamus and pituitary
70
What is the feedback loop from the hypothalamus to the adrenal gland in a patient with Cushing's Disease?
ACTH Dependent
Something is wrong with the pituitary
↑ACTH → ↑Cortisol but no feedback to inhibit hypothalamus and pituitary not able to prevent ↑Cortisol
| Corticol hyperplasia
71
What is the feedback loop from the hypothalamus to the adrenal gland in a patient with an Adrenal Tumor?
Something wrong with adrenal cortex
ACTH independent
↑Cortisol → negative feedback inhibits cortisol from pituitary but not from adrenal tumor → continuous ↑Cortisol from tumor
| Cortical Atrophy (smaller)
72
What is the feedback loop from the hypothalamus to the adrenal gland in a patient with an Ectopic Tumor?
Tumor providing additional ACTH to adrenal gland → ↑Cortisol → inhibits ACTH released from the pituitary but not from the tumor (no feedback to inhibit tumor)
| ACTH Dependent
73
What would suggest a patient has Cushing's Syndrome?
Characteristic body changes
Hypertension
Diabetes
74
How is Cushing's Syndrome diagnoses/confirmed?
HIgh cortisol in plasma, urine, or saliva
High 24 hr urinary free cortisol
Plasma ir urine tests measuring the response of Dexamethasone (DEX)
75
Why are single plasma measurements unreliable for Cushing's Syndrome Diagnosis?
Due to episodic nature of secretion and elevation during stress
76
Why is urinary measurements one of the best screening tests for Cushing's Syndrome?
Normally less than 1% of secreted cortisol is ecreted unchanged in urine
77
How is Dexamethasone (DEX) used to diagnosis Cushing's Disease?
25x more potent than cortisol
DEX has high affinity for cortisol receptor → acts like cortisol and inhibits ACTH → Cortisol should drop
If cortisol drops after step 1 → probably Cushing's Disease
Step 2 is used to differentiate Cushing's Disease vs Adrenal/Ectopic Tumor
78
What are the steps in establishing hypercortisolism?
Step 1: 1-mg overnight DEX suppression test
Step 2: 8-mg overnight DEX suppression test
79
How do we differentiate between an adrenal tumor and ectopic tumor?
Plasma ACTH and Imaging studies of abdomen or pituitary
80
What does it mean if a patient has a response to a high dose of DEX?
Hypothalamic - Pituitary Hyperfunction
Cushing's Disease
81
What does it mean if a patient has no response to a high dose of DEX?
Cause of hypercortisolism is adrenal or ectopic tumor
If ↑plasma ACTH → ectopic tumor
82
What happens to the feedback loop with a primary adrenal insufficiency?
| Addison's Disease
Problem in the adrenal gland → not enough cortisol to inhibit pituitary
83
What happens to the feedback loop with a secondary adrenal insufficiency?
Problem outside the adrenal gland → not enough ACTH or cortisol
84
# Hyposecretion
Primary Adrenal Insufficiency
| Addison's Disease. What is it? What causes it?
Autoimmune destruction of adrenal cortex
Deficiencies in cortisol, aldosterone, and adrenal androgens
Excess ACTH due to loss of. negative feedback (no cortisol to inhibit ACTH)
| Gland being destroyed by antibodies
85
# Hyposecretion
Symptoms of Primary Adrenal Insufficiency
Hyperpigmentation (esp. in traumatized areas of the skin - knuckles and albows)
Weakness
Depression
Weight loss
Hypotension
86
# Hyposecretion
Secondary adrenal insufficiency
| What causes it?
Lack of ACTH → ↓cortisol, no effect on aldosterone
Drugs, tumors and infections of the pituitary gland
87
Symptoms of Secondary Adrenal Insufficiency
Similar to those of Addison's Disease (w/o hyperpigmentation)
Mild orthostatic hypotension
Poor response to stress
88
# Distinctions between Primary and Secondary Adrenal Insufficiency
Where are primary and secondary adrenal insufficiencies seen?
Primary: Adrenal
Secondary: H-P
89
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on ACTH secretion?
Primary: ↑
Secondary: ↓
90
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on pigmentation?
Primary: ↑
Secondary: ↓
91
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on body weight?
Primary: ↓
Secondary: variable
92
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on other pituitary hormones?
Primary: no Δ
Secondary: ↓
93
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on Aldosterone?
Primary: ↓
Secondary: normal
94
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on Cortisol?
Primary: ↓↓
Secondary: moderately ↓
95
# Distinctions between Primary and Secondary Adrenal Insufficiency
What effect do primary and secondary adrenal insufficiencies have on ACTH response?
Primary: none
Secondary: sluggish
96
Cosyntroping Stimulation Test: Does adrenal cortex respond?
| Cosyntropin (synthetic ACTH)
1. Rapid Test: Screening - no response go to second test
2. Prolonged test: differential
97
Congenital Adrenal Hyperplasia
| What does it do?
Any enzyme blockage that decreases cortisol synthesis will ↑ ACTH and produce adrenal hyperplasia
Missing enzyme → keep trying to make cortisol but cant → ↑ ACTH → ↑Androgens, ↓Corticosteroids
| Absense of Cortisol
98
Classical 21-Hydroxylase Deficiency
| What is it? What does it do?
21αHydroxylase is absent and cannot convert Progesterone and 17OH-Progesterone to Aldosterone and Cortisol
↓Cortisol → no inhibition of ACTH → ↑ACTH → stimulates cholesterol → ↑Androgen
| No negative feedback to inhibit ACTH and steroid creation
99
What happens if a patient has Low cortisol and Low ACTH?
Secondary Adrenal Insufficiency
Tropic Hormone Deficiency
Problem in adrenal cortex
100
What happens if a patient has Low cortisol and High ACTH?
Primary adrenal insufficiency
Primary failure of target endocrine organ
Feedback is working, problem with adrenal gland
| Addison's disease; Congenital Hyperplasia
101
What happens if a patient has High cortisol and High ACTH?
Cushing's Syndrome
Pituitary or ectopic ACTH tumor
Autonomous secretion of tropic hormone
No feedback
102
What happens if a patient has High cortisol and Low ACTH?
Autonomous secretion of taret endocrine organ
Adrenal tumor
No feedback
Secondary
