Endocrine 4 Flashcards
1
Q
Where are the adrenal glands located?
A
Embedded above each kidney in a capsule of fat
2
Q
What are the divisions of the adrenals?
A
Cortex and medulla
3
Q
What does the adrenal cortex (outer) have a similar origin to?
A
Gonads
4
Q
What does the adrenal cortex produce? (adrenal steroids)
A
Mineralocorticoids (outer gland) – aldosterone • Glucocorticoids (middle gland) – cortisol (corticosterone) • Androgen sex steroids (inner gland) – DHEA (dehydroepiandrosterone)
5
Q
What is the adrenal medulla (inner) composed of?
A
Chromaffin cells
6
Q
Where does the adrenal medulla originate from?
A
Sympathetic nervous system
7
Q
What does the adrenal medulla produce?
A
Catecholamines
– epinephrine (adrenaline)
– norepinephrine (noradrenaline)
8
Q
What are the 3 layers / zones that the adrenal cortex consists of?
A
- Zona glomerulosa – outermost layer
- Zona fasciculata – middle and largest portion
- Zona reticularis – innermost zone
9
Q
What are the categories of adrenal steroids?
A
- Mineralocorticoids
- Glucocorticoids
- Sex hormones
10
Q
Mineralocorticoids, role and main one
A
– Mainly aldosterone
– Influence mineral balance, specifically Na+ and K+ balance
11
Q
Glucocorticoids, main one and role
A
– Primarily cortisol
– Major role in glucose metabolism as well as in protein and lipid metabolism
12
Q
What are the sex hormones of the adrenal cortex similar to?
A
To those produced by gonads
13
Q
What is the most abundant and physiologically important sex hormone produced by adrenal cortex?
A
Dehydroepiandosterone (male “sex” hormone)
14
Q
What is aldosterone?
A
A major mineralocorticoid
15
Q
What does aldosterone maintain?
A
electrolyte balance
16
Q
Aldosterone feedback
A
- low plasma Na++ or high K+
- activates renin-angiotensin system
- Angiotensin II increases aldosterone release from adrenal glands
- acts on distal renal tubules
• increase Na++ & water retention
• increase excretion of K+ & H+ ions
17
Q
What is cortisol (hydrocortisone)?
A
A major glucocorticoid in humans
18
Q
Cortisol secretion rhythm regulation
A
Diurnal rhythm
19
Q
Cortisol function
A
– plays role in stress – increase blood glucose – increase blood fatty acids – control water and electrolyte balance – anti-inflammatory/immunosuppressive
20
Q
Cortisol feedback
A
negative feedback on hypothalamus (CRH) & anterior pituitary (ACTH)
21
Q
Release of ACTH
A
Hypothalamus neurons CRF (41aa peptide) → anterior pituitary
ACTH → adrenal cortex corticosteriods
22
Q
What does the adrenal cortex (sex h)
A
Both male and female sex hormones in both sexes
23
Q
Dehydroepiandrosterone (DHEA)
A
The only adrenal sex hormone that has any biological importance
24
Q
What is dehydroepiandrosterone (DHEA) overpowered by?
A
By testicular testosterone in males
25
What does DHEA govern in femailes
– Growth of pubic and axillary hair
– Enhancement of pubertal growth spurt
– Development and maintenance of female sex drive
26
Epinepherine and Norepinerphrine primary stimulius
Activation of sympathetic nervous system by stress
27
Where is Epinephrine / Adrenaline secreted?
Into blood
28
Where is Epinephrine / Adrenaline secreted?
Into blood
28
Where is Epinephrine / Adrenaline secreted?
Into blood
29
Funciton of Epinephrine / Adrenaline x 4
– “fight-or-flight” responses
– Maintenance of arterial blood pressure
– Increases blood glucose
– Increases fat metabolism (increase blood fatty acids)
30
Glucocorticoids x 4
hydrocortisone, prednisolone, dexamethasone, betamethasone
31
Glucocorticoids clinical
Replacement therapy: in adrenal failure (Addison’s disease)
32
Anti-inflammatory/immunosuppressive disorders 'chemical' treatment
Reduce T cell proliferation, release of IL-2, TNF-a, IL-1
33
Anti-inflammatory/immunosuppressive disorders x 6
– asthma (inhaler)
– eczema (topical cream)
– arthritis (systemic injections)
– ulcerative colitis (rectal suppositories)
– prevent graft rejection of the transplant
– cancer patients (anti-emetic; reduce oedema in brain tumours)
34
Benefit vs glucocorticoid use
Benefit > Risk of glucocorticoid use
35
Risk of glucocorticoid use x 4
– Immune system limited (delay tissue repair, gastric/peptic ulcers)
– Cushing’s symptoms
– Osteoporosis (alter function of bone cells osteoblasts/osteoclasts)
– Adrenal insufficiency due to sudden withdraw
36
What activity does fludrocortisone have?
Glucocorticoid and mineralocorticoid activity
37
How is fludrocortisone used as a treatment?
Used in mineralocorticoid replacement therapy (eg) in Addison’s disease.
38
What are the 3 major targets of mineralocorticoids?
Kidneys, bladder and colon
39
Addison’s disease hormone levels
Low glucocorticoid (cortisol) & mineralocorticoid (aldosterone)
40
Cause of primary Addison’s disease
Damage adrenal gland (TB or autoimmunity)
41
Cause of secondary Addison’s disease
Low ACTH release
42
Symptoms of Addison’s disease
* hypoglycaemia
* decreased liver glycogen
* fatigue, anorexia, nausea, weight loss, dizziness, hypotension, psychiatric
* death if untreated
43
Treatment for Addison's disease
Steroid replacement therapy
44
Cushing’s disease hormone levels
Excess glucocorticoids (cortisol)
45
Cause of Cushing’s disease
ACTH secreting tumor in pituitary
46
Symptoms of Cushing's disease
* hyperglycemia
* elevated blood pressure
* obesity (abdominal fat, thin arms & legs)
* muscle wasting, osteoporosis, cataracts
* poor wound healing
* buffalo hump, moon face, red cheeks
* psychiatric symptoms (depression, euphoria, hallucinations)
47
Treatment for Cushing's disease
* remove tumor
* antiglucocorticoids
* surgical adrenalectomy
48
Hyperplastic of adrenal cortex image
49
Conn's syndrome hormone levels
Excessive mineralocortocoids (aldosterone)
50
Primary Conn's syndrome cause
tumour
51
Secondary Conn's syndrome cause
Excessive renin-angiotensin action in kidney disease, cirrhosis of liver, congestive heart failure
52
Symptoms of Conn's syndrome
* sodium and water retention
| * increase in extracellular fluid and hypertension
53
Treatment for Conn's syndrome
* antagonist of aldosterone (spirono-lactone)
| * unilateral adrenalectomy
54
generalised stress response LEARN
* ↑ epinephrine secretion from adrenal medulla (chromaffin cells)
* ↑ CRH-ACTH-cortisol (HPA axis) that mobilises metabolic resources
* ↓ insulin & ↑ glucagon secretion to raise blood glucose & fatty acids
* ↑ renin-angiotensin-aldosterone system & vasopressin secretion to maintain blood volume and blood pressure
55
What does chronic stress cause?
Causes heart disease, hypertension, atherosclerosis, immune-suppression
56
What does prolonged release of CRH cause?
Anxiety & depression
57
What may CRF1 receptor antagonists treat?
Anxiety, depression, drug dependence and irritable bowel syndrome
58
Stress response from hypothalamus diagram
59
Cortisol feedback
60
Main glucocorticoids
Cortisol
61
Upstream hormones of cortisol
Adreno-corticotropic Hormone (ACTH)
62
Hypersecretion of cortisol causes
Cushing’s disease (high glucocorticoids)
63
Hyposecretion of cortisol causes
Addison’s disease
| low corticoids
64
Main mineralocorticoids
Aldosterone
65
Upstream hormones of Aldosterone
Angiotensin II
66
Hypersecretion of aldosterone causes...
Conn’s Syndrome (high mineralocortocoids)
67
Hyposecretion of aldosterone causes...
Addison’s disease (low corticoids)
68
Hyposecretion of aldosterone causes...
Addison’s disease (low corticoids)
69
Fed state
Store amino acids, glucose and triglycerides
70
Hungary state
Mobilise stored reserves
71
Tissue to breakdown in blood diagram
72
Glycogenesis reaction
Glucose → glycogen
73
Glycogenolysis reaction
Glycogen → glucose
74
Gluconeogenesis reaction
Amino acids → glucose
75
Protein synthesis reaction
Amino acids → protein
76
Protein degradation
Protein → amino acids
77
Fat synthesis (Lipogenesis or Triglyceride synthesis)
Fatty acids and glycerol → triglycerides
78
Fat breakdown (Lipolysis or Triglyceride degradation)
Triglycerides → fatty acids and glycerol
79
Blood consequence of glycogenesis
↓ blood glucose
80
Blood consequence of protein synthesis
↓ Blood amino acids
81
Blood consequence of fat synthesis
↓ Blood fatty acids
82
Blood consequence of glycogenolysis
↑ Blood glucose
83
Blood consequence gluconeogenesis
↑ Blood glucose
84
Blood consequence of protein degradation
↑ Blood amino acids
85
Blood consequence of fat breakdown
↑ Blood fatty acids
86
Anabolism defn
Build up or synthesis of larger organic macromolecules from small organic subunits
87
Anabolism require..
ATP
88
Anabolism results in...
* Manufacture of materials needed by the cell
* Storage of excess ingested nutrients not immediately needed for energy production or needed as cellular building blocks
89
Catabolism defn
Breakdown or degradation of large energy rich organic molecules within cells
90
The two levels of catalytic breakdown are ....
* Hydrolysis of large cellular molecules into smaller subunits
* Oxidation of smaller subunits to yield energy for ATP production
91
Summary of the major pathways involving organic nutrient molecules diagram
92
Where does most interconversion of organic molecules occur?
In the liver
93
What happens to excess circulating glucose?
* Stored in liver and muscle as glycogen
* Once liver and muscle stores are “filled up”, additional glucose is transformed into fatty acids and glycerol and stored in adipose tissue
94
What happens to excess circulating fatty acids?
Becomes incorporated into triglycerides
95
What happens to excess circulating amino acids?
Converted to glucose and fatty acids
96
What is the circulating form of carbohydrate?
Glucose
97
What is the circulating form of fat?
Free fatty acids
98
What is the circulating form of protein?
Amino acids
99
What is the storage from of carbohydrate?
Glycogen
100
What is the storage from of fat?
Truglycerides
101
What is the storage from of protein?
Body proteins
102
What is the major storage site of carbohydrate?
Liver, muscle
103
What is the major storage site of fat?
Adipose tissue
104
What is the major storage site of protein?
Muscle
105
Carbohydrate percentage of total body energy content
1%
106
Fat percentage of total body energy content
77%
107
Protein percentage of total body energy content
22%
108
Reservoir capacity of carbohydrate
Less than a day's worth of energy
109
Reservoir capacity of fat
About two months' worth of energy
110
Reservoir capacity of protein
Death results long before capacity is fully used because of structural and functional impairment
111
Role of carbohydrate
First energy source, essential for brain
112
Role of fat
Primary energy reservoir, energy source during a fast
113
Role of protein
Source of glucose for the brain during a fast; last resort to meet other energy needs
114
Role of liver in metabolic states
- Primary role in maintaining normal blood glucose levels
| - Principal site for metabolic interconversions such as gluconeogenesis
115
Role of adipose tissue in metabolic states
- Primary energy storage site
| - Important in regulating fatty acid levels in the blood
116
Role of muscle in metabolic states
Muscle
- Primary site of amino acid storage
- Major energy user
117
Role of brain in metabolic states
- Normal can only use glucose as an energy source
- Does not store glycogen
Mandatory blood glucose levels be maintained
118
Factors that increase blood glucose
- Glucose absorption from digestive tract
- Hepatic glucose production; Through glycogenolysis and
gluconeogenesis
119
Factors that decrease blood glucose
- Transport of glucose into cells: for utilisation for energy production and for storage as glycogen through glycogenesis and as triglycerides.
- Urinary excretion of glucose
120
Hormones regulating metabolism
- Anterior Pituitary gland
- Growth hormone, ACTH, TSH
- Liver
- Somatomedins (IGF’s)
- Thyroid gland (T3 T4 )
- Thyroxine
- Gonads
- Sex steroids
- Adrenal cortex
- Glucocorticoids (cortisol)
- Adrenal medulla
- adrenaline (noradrenaline)
- Pancreatic (Islets of Langerhans)
- Insulin & glucagon
121
What do exocrine cells of islets of langerhans secrete?
Proteases into small intestine
122
How much of pancrease does the endocrine Islet of Langerhans comprise?
1%
123
What is the endocrine Islet of Langerhans surrounded by?
Capsule
124
Where are endocrine Islet of Langerhans located?
Scattered throughout pancreas
125
Endocrine Islet of Langerhans blood supply function
Rich blood supply for hormone drainage
126
Endocrine Islet of Langerhans composition
Clusters composed ~3000 endocrine secretory cells
127
What does pancreas removal cause
Symptoms of diabetes
| ↑[glucose]plasma 20-30mM
128
Location and structure of the pancreas diagram
129
Cell types in the islets of Langerhans diagram
130
3 secretory cells of islets of Langerhans
─ β cells
─ α cells
─ δ cells
131
What do the secretory cells of islets of Langerhans produce?
peptide hormones
132
Beta cells function
Insulin production - promotes glucose uptake
133
Alpha cells function
Glucagon production - opposite effect to insulin
134
Delta cells function
Somatostatin production -
| potentiates glycogen breakdown activity of glucagon
135
Where is insulin stored and secreted from?
Cytoplasmic granules
136
Insulin fed state
Anabolic hormone
137
Insulin in fed state effects
- Glucose to glycogen
- Fatty acids to triglycerides
- Amino acid to protein
138
'Organ' effects of insulin
- ↓ glucose, amino acid and fatty acid in blood
- ↑ glucose, amino acid and fatty acid uptake in muscle
- ↓ breakdown of glycogen, fat (triglycerides) and protein
139
Glucagon in hungry state
Catabolic hormone
140
Effects of glucagon
- Glycogen to glucose
- Triglycerides to fatty acids
- Protein to amino acid
141
Effects of glucagon in blood
- ↑ glucose, amino acid and fatty acid in blood
- ↓ glucose, amino acid and fatty acid uptake in muscle
- ↑ breakdown of glycogen, fat (triglycerides) and protein
142
glycogenolysis/lytic
glycogen breakdown
143
gluconeogenesis
glucose synthesis
144
gluconeogenesis
glucose synthesis
145
lipolysis
lipid/fat breakdown
146
lipogenesis
Lipid/fat synthesis
147
What is insulin synthesised as?
Prohormone
148
What is insulin cleaved to?
Mature peptide
149
Half life of insulin and glucagon
I - t1/2 = 30 minutes
| G - t1/2 = 10 minutes
150
Stimulation of insulin secretion by glucose via excitation secretion couplinf
1. Glucose enters Beta cells by diffusion via GLUT- 2. Glucose is phosphorylated to glucose-6-phosphate.
3. Oxidation of glucose-6-phosphate produces ATP.
4. ATP acts on ATP-sensitive K+ channels, closing it.
5. Reduced exit of K+ depolarises membrane.
6. Depolarisation opens voltage-gated Ca2+ channels.
7. Ca2+ enters Beta cell.
8. Ca2+ triggers exocytosis of insulin vesicles.
9. Insulin is secreted
151
Factors controlling insulin secretion
152
What is the most common of all endocrine disorders?
Diabetes Mellitus
153
Most prominent feature of Diabetes Mellitus?
Hyperglycemia
154
What is hyperglycemia
Elevated blood sugar
155
What is the only hormones capable of lowering blood sugar
Insulin
156
2 varients of Diabetes Mellitus
Type 1 Diabetes and Type 2 Diabetes
157
Diabetes word meaning
“siphon” or “running through” – reference to the large urine volume accompanying this condition
158
Mellitus work meaning
“sweet” – acquires its sweetness from secretion of excess glucose in this condition
159
x 6 points about Type 1 diabetes
- Symptoms develop rapidly
- Childhood onset
- Affects 10-20% diabetics
- Loss of b cell function
- Insulin secretion none/low
- Insulin injections for treatment
160
x 6 points about Type 2 diabetes
- Symptoms develop slowly
- Adulthood onset
- Affects 80-90% diabetics
- Insulin insensitivity
- Insulin secretion normal/high
- Treatment - diet/exercise and oral drugs
161
4 effects of severe diabetes
1. Excessive eating
2. Dehydration and thirst
3. Coma
4. Brain cells are glucose obligate cells
162
Excessive eating in severe diabetes
- Cells starved of carbohydrate
| - Hypothalamic center leads to excessive eating
163
Dehydration and thirst in severe diabetes
- Low glucose uptake, blood glucose rises
- Glucose appears in urine, increases urinary vol
- Dehydration and thirst
164
Coma in severe diabetes
- Cells unable to use glucose increases
- Lipolysis generates fatty acids and ketoacids
- Ketoacids lower blood pH
- Decreased brain O2 and coma
165
Brain cells are glucose obligate cells in severe diabetes
- Low glucose, brain stops working
| - Coma and respiratory paralysis
166
Glucose tolerance test chart
167
Counteracting actions of glucagon and
Insulin on blood glucose during absorption
of a high protein meal. diagram
168
slide
42 finish it lol
