Exam 2 Flashcards
(359 cards)
1
Q
What are the two parts of the adrenal (suprarenal) glands
A
Cortex
Medulla
2
Q
Function of cortex in the adrenal glands
A
Secretes corticosteroids derived from cholesterol
3
Q
Function of medulla in the adrenal glands
A
Secretes catecholamines derived from tyrosine
4
Q
Corticosteroids released from the adrenal cortex (3)
A
Glucocorticoids (eg- Cortisol) Mineralcorticoids (ex- Aldosterone) Sex steroids (testosterone)
5
Q
Catecholamines secreted from the adrenal medulla (2)
A
Epinephrine and norepinephrine
6
Q
Layers of the adrenal cortex (superficial to deep)
A
Zona glomerulosa
Zona fasciculata
Zona Reticularis
7
Q
Layers of the adrenal glands
A
Capsule
Adrenal cortex
Adrenal medulla
8
Q
Zona glomerulosa is ____% of the adrenal cortex thickness
A
15%
9
Q
What does the Zona glomerulosa secrete? What is the primary hormone?
A
Mineralocorticoids
Primary hormone = aldosterone
10
Q
What stimulates aldosterone release?
A
Angiotensin II and Potassium
11
Q
Function of Aldosterone
A
Controls blood pressure and blood volume
Controls electrolyte balance through the kidney
Causes reabsorption of Na, Cl, H20
And excretion of K and H
12
Q
______% of adrenal cortex thickness is the Zona fasciculata
A
75%
13
Q
Zona fasciculata secretes:
Its primary hormone is:
A
Glucocorticoids
Primary hormone is cortisol (stress hormone)
14
Q
The zona fasciculata is under what control?
A
Hypothalamic-pituitary axis control (CRH and ACTH)
Cortisol provides negative feedback to the hypothalamus and the anterior pituitary
15
Q
______% of thickness in the adrenal cortex that is the zona reticularis
A
10%
16
Q
What does the zona reticularis secrete?
Primary hormones?
A
Adrogens
DHEA (dehydroepiandosterone) and androstenedione
17
Q
Zona Reticularis control mechanism is influenced by:
A
ACTH
18
Q
Dihydrotesterone and estradiol synthesis occur where?
A
In peripheral tissues and gonads
19
Q
How is pregnenolone made?
A
Cholesterol enters mitochondria of cells and is cleaved by cholesterol desmolase (P-450scc)
20
Q
Rate limiting step in adrenal steroid production .
Why?
A
Synthesis of pregnolone
It can be converted into any of the other steroid hormones
21
Q
Adrenal cholesterol is most provided by:
A
Blood LDL
22
Q
Adrenal cholesterol is obtained by:
A
Receptor mediated endocytosis (rate influenced by ACTH)
23
Q
______ release cholesterol from the endosomes
A
Lysosomes
24
Q
Synthesis of hormones occurs where?
A
In mitochondria and ER
25
Aldosterone- ____% of all mineralcorticoid activity. Very ___
90%
| Potent
26
Mineralocorticoids (5)
```
Aldosterone
Cortisol
Corticosterone
Cortisone
Deoxycorticosterone
```
27
Aldosterone synthesis steps
```
Cholesterol
To pregnenolone
Progesterone
11-Deoxycortocosterone DOC
Corticosterone
18 (OH) Corticosterone
Aldosterone
```
28
Cortisol- ____% of ______ activity, very potent
95%
glucocorticoid
29
Glucocorticoid minor in humans
Corticosterone
30
Glucocorticoids that are almost as potent as cortisol
Cortisone
31
Synthetic glucocorticoids
Prednisone (cortisol X 4)
Methylprednisone (Cortisol X 5)
Dexamethason (Cortisol X 30)
32
90-95% of cortisol is bound to:
Some to:
The rest:
Transcortin (cortisol-binding globulin)
Some to albumin
The rest (tiny amount) as free cortisol
33
Half life of cortisol
60-90 min
34
60% of aldosterone is bound to _____
40 % :
Half life is:
Albumin
Free aldosterone
20 min
35
Transcortin is produced where?
In the liver
36
________ proteins slow hormone inactivation. They help maintain:
Trasport proteins
Helps maintain hormones in circulation
37
All adrenal cortical hormones are metabolized to :
Inactive conjugated forms in the liver (mostly conjugated with glucuronic acid)
38
25% of inactive conjugated forms are excreted where?
The remaining are excreted:
Into bile
In the urine
39
Cortisol also binds to _________ receptors
Mineralocorticoids receptors
40
What has greater activity than cortisol?
Aldosterone (3000x greater)
41
Kidney has a receptor to metabolize ______ to _____
Cortisol to cortisone (11beta-hydroxysteroid) which nullifies most of cortisol’s mineralocorticoid effects there.
42
Aldosterone has effects on:
Sweat glands, salivary glands, intestinal epithelial cells
43
What are aldosterone’s effects on the kidney?
Increases renal tubular reabsorption of sodium and potassium secretion - especially in the principal cells of the distal tubules and collecting tubules
Also stimulates secretion of H+ via H+/ATPase in the intercalated cells of collecting tubules
44
Aldosterone antagonists
Spironalctone
| Eplerenone
45
Sodium channel blockers
Amiloride
| Triamterene
46
ECT sodium concentration only ____ slightly with:
Rises
Increased aldosterone secretion
47
What are physiologic mechanisms that keep sodium concentration for getting too high?
What are these called?
Osmotic absorption of water
Increased thirst and water intake
Resulting volume/pressure increase stimulates pressure disrespect and natriuresis
Called the “aldosterone escape”
48
Diseases of excess aldosterone
Hypokalemia
| Alkalosis
49
Hypokalemia is due to:
| It causes:
Increased loss of K+ in the urine and uptake into cells
| Causes severe muscle weakness
50
Alkalosis is due to:
Stimulation of H+ pump in intercalated cells
51
Diseases of deficient aldosterone
Hyperkalemia
NaCl depletion and blood volume depletion progressing to shock
52
Hyperkalemia is due to:
Retention of K+ in the ECF
| Cardiac toxicity
53
How does aldosterone increase reabsorption of NaCl and secretion of K+?
By the ducts of the salivary glands and sweat glands (helps to conserve Na+ in times if increased secretion of sweat or saliva)
54
Where does aldosterone enhance Na+ absorption? What does this lead to?
By the intestines
| Leads to the absorption water and Cl- (and other anions)
55
What would happen to the intestines without aldosterone
NaCl and water are unabsorbed which will lead to diarrhea
56
How does aldosterone enter the cell?
Diffusion
57
Receptor that binds with aldosterone
Mineralocorticoid receptor (MR)
58
After MR/aldosterone complex diffuses into the nucleus, what is induced?
DNA transcription into mRNA
Which is then translated into proteins such as: Na+/K+ ATPase and epithelial sodium channels
59
What increases aldosterone secretion?
Increased K+ concentration in the ECF
And
Angiotensin II concentration in the ECF
60
What slightly decreases aldosterone secretion?
Increased Na+ ion concentration in the ECF
61
What is necessary for aldosterone secretion?
ACTH from the anterior pituitary gland
| But it has little effect in controlling the RATE of secretion
62
At least 90% of glucocorticoid activity is due to:
Cortisol (aka hydrocortisone)
63
_____ provides a smaller amount of glucocorticoid activity?
Corticosterone
64
Cortisol effects what 4 things?
Carbohydrate metabolism
Protein metabolism
Fat metabolism
Stress and inflammation resistance
65
Cortisol and carbohydrate metabolism stimulates:
Gluconeogenesis
66
Gluconeogenesis induces
Production of enzymes in the liver to convert amino acids into glucose
Mobilization of amino acids from tissues outside liver (mainly muscle)
67
Newly made glucose is stored largely as:
Glycogen in the liver; access by epinephrine and glucagon as needed
68
Decreased glucose utilization by cells is likely due to
inhibition of NADH oxidation
69
Elevated blood glucose is due to:
The combined effects of gluconeogenesis and decreases glucose utilization of cells
70
Elevated blood glucose causes
Insulin secretion (Cortisol also decreases insulin sensitivity)
71
Excess in cortisol secretion causes:
Adrenal diabetes
72
Reduction of cellular protein (DOES/DOES NOT) occur in the liver.
What does this do the protein?
Does not
Decreases protein synthesis
Increases protein catabolism
73
Excess of cellular protein can cause
Severe weakness
74
The liver (INCREASES/DECREASES) plasma protein production
Increases
75
Since plasma proteins are largely produced by the _______, they increase in the _______.
Liver
| Blood
76
Increased blood amino acids decrease:
They increase:
Decrease transport of amino acids into extrahepatic cells
Increase release of amino acids into blood from protein catabolism
77
Amino acids in the liver are used for what?
To make plasma proteins, increase protein synthesis and for gluconeogenesis
78
Cortisol causes
- Release of free fatty acids from:
- increased _____ of fatty acids in cells
Adipocytes
Oxidation
79
Excess cortisol leads to fat:
Accumulation in the face and torso
80
In regards to fat, glucose causes:
Decreased glucose utilization
Decreased sensitivity to insulin
Increased lypolysis
Release of:
Glycerol
81
In regards to muscle, increase of glucose causes:
Increase in:
Protein degradation
Decrease in:
Protein synthesis
Glucose utilization
Sensitivity to insulin
Release of:
Amino acids
82
In the liver, increased amino acids and glycerol causes:
```
Increase in:
Glycogen storage
Gluconeogenesis
Activity of enzymes
Amounts of enzymes
```
Release of:
Glucose
83
Types of stress (physical or neurogenic)
Trauma or surgery
Infection of any debilitating disease
Intense heat or cold
Psychological distress
84
Stress causes increase in:
ACTH secretion which then increases cortisol secretion
85
Stages of inflammation (5)
Inflammatory cells release histamine, bradykinin, prostaglandins, etc. (pain)
Increase in blood flow (erythema, heat)
Increased permeability, leakage of plasma into ISF including protein (edema)
Infiltration by leukocytes
Ingrowth of fibrous tissue and healing
86
2 basic anti inflammatory effects of cortisol
1- block early stages of inflammation (prevention of inflammation)
2- Causes rapid resolution of inflammation to allow healing
87
Inflammation prevention...
- stabilizes _________
- decreases ______
- decreases________
- suppresses___________
- Lowers ______
```
Stabilizes lysosomal membranes
Decreases capillary permeability
Decreases migration of leukocytes
Suppresses the immune system
Lowers fever
```
88
What are the two ways of resolving inflammation?
Blocks inflammatory mediators
| Speeds healing by mobilization of aa for tissue repair and increasing glucose and FA
89
_______ are given therapeutically to reduce inflammation
Glucocorticoids
90
T or F: glucocorticoids fixes the underlying problem of inflammation
False; glucocorticoids DOESNT fix the underlying problem of inflammation just reduces it therapeutically
91
Most metabolic effects of steroid hormones require ______ minutes for proteins to be synthesized and ________ for full effect
45-60 min
Hours-days
92
________ from the AP (anteiror pituitary) stimulates cortisol secretion
ACTH (corticotropin)
93
What mechanism is used to stimulate cortisol release via ACTH?
Adenylyl cyclase/ cAMP
94
_________ leads to the activation of ________ which converts cholesterol to pregnenolone
PKA; desmolase
95
______ is inturn controlled by corticotropin releasing factor (CRH) from the hypothalamus
ACTH
96
Cortisol excess exerts negative feedback on what glands?
Pituitary gland and hypothalamus
97
_______ inhibits the hypothalamus and anterior pituitary
Cortisol
98
Pain from physical damage is transmitted to the ________
***stress source
Median eminence
99
Mental stress from the __________ is transmitted to the _________
Limbic system; posterior medial hypothalamus
100
_________ is the precursor to ACTH
Pro-opiomelanocortin (POMC)
101
POMC also produces what hormones other than ACTH?
Melanocytes stimulating hormone (MSH)
Lipotropin
Endorphin
102
Cortisol stabilizes:
| This decreases:
Lysosomal membranes
Decreases release of pro-inflammatory enzymes
103
Cortisol decreases:
Capillary permeability
Migration of leukocytes
104
How does cortisol decrease migration of leukocytes?
By blocking inflammatory mediators
105
Cortisol suppresses what system
The immune system (especially T cells)
106
How does cortisol lower fever?
By decreasing IL-1 production
107
Cortisol inactivates or removes:
Inflammatory products
108
Cortisol speeds healing by:
Mobilization of amino acids for tissue repair
Increasing glucose and fatty acid availability for critical systems
109
Glucocorticoids are given therapeutically to:
Reduce inflammation
110
DHEA and androstenedione are continually secreted by ________, especially during:
Zona Reticularis
Fetal development
111
Much of pubic and axillary hair in remains is due to
Adrenal adrogens
112
Small amounts of ____ and _____ are secreted from the adrenals
Estrogens
Progesterone
113
Most abundant steroid hormone
DHEA
114
DHEA causes cells to make
Testosterone and estradiol
115
DHEA levels decline with:
Age, stress and disease
Lower levels associate with increased disease and increased mortality
116
DHEA’s association with cortisol
It balances and counteracts cortisol’s effects
117
DHEA reduces
Pain and inflammation
118
DHEA improves:
Immune system function,
And, in women, fertility and sexual function
119
Addison’s disease, AKA:
Hypoadrenalism
120
Primary hypoadrenalism
Autoimmunity causes atrophy of the adrenal glands
Destruction of tumor or tuberculosis
121
Secondary hypoadrenalism
Impaired pituitary and decreased release of ACTH
122
Symptoms of Addison’s disease
Bronze pigmentation of skin
Hypoglycemia
Changes in distribution of body hair
Postural hypotension
GI disturbances
Weight loss
Weakness
123
Adrenal crisis in Addison’s disease
Profund fatigue
Dehydration
Vascular collapse (decreased BP)
Renal shut down
Decreased serum NA
Increased serum K
124
Mineralocorticoid deficiency :
| Decreased:
ECF volume, hypotension
Cardiac output- shock and death
125
______ and ______ are continually secreted by the zona reticularis especially during fetal development
DHEA and androstenedione
126
Testosterone and estradiol are synthesized from _____
DHEA
127
Levels of DHEA _____ with age, stress, and disease
Decline
128
______ balances and counteracts cortisol effects
DHEA
129
_______ reduces pain and inflammation, improves immune system functions and improves fertility and sexual function
DHEA
130
What is the disease associated with hypoadrenalism?
Addison’s disease
131
What is the disease associated with hyperadrenalism?
Cushing syndrome
132
What is primary Addison’s disease? (Hypoadrenalism)
Autoimmunity causes atrophy of the adrenal glands
| Destruction by tumor or tuberculosis
133
Symptoms of Mineralocorticoid deficiency
Hyponatremia
Hyperkalemia
Acidosis
134
Review slide 49 for glucocorticoid deficiency
Review slide 49
135
In primary hypoadrenalism, _______ levels are high, causing MSH to be hyper-secreted
ACTH
136
Hyperadrenalism, AKA
Cushing’s syndrome
137
Causes of Cushing’s syndrome
Adenoma of the ant. Pituitary- secretes too much ACTH (most common)
Hypothalamus produces too much CRH (Rare)
Tumor elsewhere in the body secretes ACTH
Adenoma of the adrenal cortex- secretes too much cortisol
Prolonged glucocorticoid therapy
138
Symptoms of Cushing’s syndrome
“Buffalo torso” and “moon face”
Acne and excess facial hair
Hyperglycemia (adrenal diabetes)
Severe weakness from protein depletion in the muscles
Osteoporosis (lack of collagen)
Purple stria (tearing of subcutaneous tissue)
139
What causes buffalo torso and moon face in cushing’s syndrome?
Mobilization of fat from the extremities to the trunk and edema
140
Primary aldosteronism, AKA
Conn’s syndrome
141
Causes of conn’s syndrome
Tumor of zona glomerulosa
Hypersecretion of aldosterone
142
Features of Conn’s syndrome (6)
Hypokalemia
Metabolic Alkalosis
Slight increase in ECF and blood volume
Hypertension
Periodic muscle paralysis from hypokalemia
Decreased renin production
143
Conn’s syndrome should be considered in any hypertensive pt with:
Muscle weakness, polydipsia, and/or hypokalemia
144
Causes of Conn’s syndrome
75%- Adrenal adenoma
25%- Adrenal hyperplasia
Rarely- Adrenocortical cancer
145
Adrenal medulla is usually studied along with the:
Autonomic nervous system
146
Catecholamines synthesis occurs where?
From what?
In the cytoplasm of chromatin cells
From tyrosine
147
Stimulation of release of catecholamines
Direct sympathetic innervation
148
Alpha 1,2 receptors are used for: (6)
```
Vasoconstriction
Iris dilation
Intestinal relaxation
Bronchoconstriction
Increased heart contractility
Hepatic glucose production
```
149
Beta 1,2 receptors stimulate (7)
```
Vasodilation
Increased heart rate
Increased heart contractility
Intestinal relaxation
Bronchodilator
Glycogenolysis
Lipolysis
```
150
Steps of short term stress response
1- hypothalamus sends nerve signals via spinal cord
2- nerve signals are sent to adrenal medulla
3- epinephrine and norepinephrine are secreted
151
Long term stress response steps
1- Hypothalamus stimulates anterior pituitary with releasing hormone
2- anterior pituitary releases ACTH into blood
3- ACTH sent to the adrenal cortex
4- Corticosteroids are released into bloodstream
152
Review slide 57
Review slide 57
153
Pheochromocytoma, AKA:
Catecholamine- secreting adrenal tumor
154
Epidemiology of Pheochromocytoma
Adults- both sexes, all ages (especially 30-50 years)
155
Biological behavior of Pheochromocytoma
90% benign, 10% malignant
156
Pheochromocytoma secretes high levels of ________, most secrete ________
High levels of catecholamines, most secrete norepinephrine.
157
Clinical presentation of Pheochromocytoma
Episodic or sustained hypertension, sweating, palpitations, hyperglycemia, glycosuria
158
Macroscopic features of Pheochromocytoma
Mass, often hemorrhagic; 10% bilateral; 10% extra-adrenal
159
Microscopic features of Pheochromocytoma
Nests of large cells, vascular stroma
160
Excess inflammation can cause
Can prevent or slow healing
161
Most metabolic effects of cortisol require ______ (time) for proteins to be synthesized, and (time) for full effect
45-60 min
Hours-days
162
For steroid hormone metabolism:
The hormone enters the ______, and attaches to the _____ _____.
This creates a _____ _____ ____.
Cytoplasm
Steroid receptor
Hormone-receptor complex
163
For steroid hormone synthesis:
| After binding to the steroid receptor in the cytoplasm, what happens to the hormone-receptor complex?
It enters the nucleus
Here it binds to receptor sites on chromatid, activating mRNA transcription
164
ACTH aka:
Corticotropin
165
ACTH comes from the:
It stimulates :
Anterior pituitary
| Cortisol secretion
166
How does ACTH stimulate cortisol secretion
Adenylyl Cyclase/cAMP mechanism
Protein kinase A leads to activation of desmolase, which converts cholesterol to prefnenolone
167
ACTH is controlled by ______ which is secreted by the ______
Corticotropin releasing factor
Hypothalamus
168
Review slide 44
Review slide 44
169
Cortisol inhibits the:
Hypothalamus and anterior pituitary
170
Cortisol stimulates (4)
Gluconeogenesis
Protein mobilization
Fat mobilization
Stabilizes lysosomes
171
Stress sources for pain:
Mental stress:
Pain- from physical damage - transmitted to the median eminence
Mental stress- From the lambic system
- transmitted to the posterior medial hypothalamus
172
Precursor to ACTH
Pro-opiomelanocortin (POMC)
173
Breakdown of POMC also produces
Melanocyte stimulating hormone
Lipotropin
Endorphin
And a few others
174
When ACTH rate is high, this means that:
Other POMC products may also be overproduced
175
What type of gland is the pancreas
Both endocrine and exocrine
176
Pancreatic acini is (ENDOCRINE/EXOCRINE)
| Secretes:
Exocrine
Digestive juices
177
Islets of Langerhans is (ENDOCRINE/EXOCRINE)
Cells inside them
Endocrine
Alpha cells
Beta Cells
Delta Cells
178
Alpha cells in the pancreas (islets) release
Glucagon
179
Beta cells in the pancreas (islets) release:
Insulin, amylin
180
Delta cells in the pancreas (Islets) releases
Somatostatin
181
Insulin is associated with:
Energy abundance
182
Insulin is secreted when?
When energy rich foods are eaten (especially carbohydrates)
Stimulated by high blood glucose
183
Insulin promotes:
Storage of excess energy
184
Insulin effects in the liver
Glucose -> Glycogen
185
Insulin effects in adipocytes
Fatty acids -> TAGs
186
Insulin effects of other cells
Amino acids -> protein
187
After translation, insulin is initially
Preproinsulin
188
Preproinsulling is cleaved in the ______, to form:
ER
| Proinsulin
189
Proinsulin is cleaved in the _______ into:
Golgi
| Insulin and “C pepetide”
190
What happens to insulin once cleaved?
It is packaged into secretory vesicles
When released, it circulates unbound
191
Half life of insulin
Approx 6 min
192
C peptide binds to a ____ _____ and activates
Membrane receptor
Some enzymes
193
How is c-peptide used clinically?
Used as a measurement in insulin-treated patients
Can be assessed for any endogenous insulin production
194
C peptide is useful for
Monitoring beta cell function in people with diabetes who are on insulin therapy
195
Insulin receptor has ___ subunits
4
196
What type of receptor is an insulin receptor
Enzyme-linked
197
Autophosphorylation of the insulin receptor activates:
Tyrosine kinase
198
Tyrosine kinase activates
Tissue specific IRS (insulin receptor substrate) enzymes
199
Insulin receptor substrates:
```
Growth and gene expression
Glycogen synthesis
Fat synthesis
Protein synthesis
Glucose transport
```
200
____% of body cells increase glucose uptake
80
201
Glucose uptake- most profound effect is in:
Muscle and fat
202
Most brain cells are _____ independent
Insulin
203
Mechanism of glucose uptake
Fusion of vesicles containing glucose (GLUT4)
| Transport proteins to the cell membrane
204
GLUT1 is responsible for:
Baseline uptake
***Ubiquitous and present in many cells
205
GLUT2 is found where?
Liver
Kidney
Pancreatic Beta cells
Intestine
THIS IS BI-DIRECTIONAL
206
GLUT3 found in:
Neuron
Placenta
Has high affinity
207
GLUT 4 found in
It is ______ dependant
All muscles
Adipocytes
Heart
Insulin dependant
208
Muscle mostly depends on _____ ______ between meals
Fatty acids
209
Circumstances when muscle uses more glucose
Exercise- Increases permeability to glucose
After a meal- Insulin increases glucose uptake, then stored as glycogen if not needed
210
Mechanism of storing glucose as glycogen in the liver
Insulin inactivates glycogen phosphorylase
Stimulates glucokinase
Stimulates glycogen synthase
211
What happens to excess glucose after glycogen is maximized
It is converted to fatty acids (VLDL)
212
What happens in the liver when there is lack of insulin
Reverse effects on phosphorylase, glucokinase and glycogen synthase
Glycogen is broken down
213
What is activated to release glucose into the blood? Why?
Glucose phosphates
Insulin is low.
214
Most brain cells are permeable to _____ and do not need ____
Glucose
Insulin
215
Brain normally only uses glucose for _______, therefore depends on:
Energy
Blood glucose
216
When blood glucose falls to low in the brain, what happens?
Hypoglycemic shock occurs (fainting, seizures and coma)
217
Insulin in adipose promotes:
Fatty acid synthesis by liver that is then transported to fat cells (VLDL)
Also glucose transport into fat cells, mostly to form glycerol
218
Insulin in adipose inhibits
Hormone-sensitive lipase (HSL), thereby inhibiting release of fat from adipocytes
219
For protein metabolism, insulin promotes:
It prevents:
Promotes protein formation
Prevents protein degradation
220
For protein metabolism, insulin stimulates:
It inhibits:
Amino acid uptake by cells
Protein catabolism
221
For protein metabolism, insulin increases:
It decreases:
mRNA translation into new protein
And
Gene expression for enzymes needed for carb, fat, and protein storage
Decreases: Liver gluconeogenesis (amino acids are NOT converted to sugar)
222
What causes weight gain the most?
Growth hormone AND insulin together
223
When insulin is deficient, what happens to hormone sensitive lipase
It becomes active, releases large amounts of fatty acids and glycerol into the blood
224
When insulin is deficient, what happens to glucose concentrations?
They rise
225
When insulin is deficient, what happens to plasma cholesterol and phospholipids?
They rise- accelerating atherosclerosis
226
Excessive beta oxidation of fats in the liver creates:
Excess acetyl-CoA, which is then converted to Acetoacetic acid
227
What happens to excess acetoacetic acid that cannot be metabolized back to acetyl-CoA in other tissues
It forms ketone bodies (Beta-hydroxybutyric acid and acetone)
228
Ketoacidosis may lead to:
Coma and death
229
Acetoacetate is created from:
It is converted into:
Breakdown of fatty acids
Into BHB or turned into acetone
230
Beta-hydroxybutyric acid formed from:
Why is this not technically a ketone?
Acetoacetate
Because of its structure- we consider it as one within the keto diet
231
Acetone is created as:
It breaks down:
How is it removed?
As a side product of acetoacetate
Quickly
From the body through the waste or the breath
232
Norepinephrine ->normetanephrine via what enzyme?
Epinephrine-> metanerphine via what enzyme
COMT (catechol-O-methyltransferse)
COMT
232
Epinephrine and norepinephrine are converted to dihydroxymanfdelic acid via what enzyme?
MAO ( monoamine oxidase)
233
What happens when there is a protein depletion and increased plasma amino acids?
Catabolism of proteins increase
Large amounts of amino acids are released into the plasma
Some amino acids are used for gluconeogenesis (also glycerol and lactic acid)
234
Glucose enters/leaves the pancreatic beta cell via the
GLUT 2 channel
235
What happens with pancreatic beta cell when blood glucose is high
More glucose enters the cell, stimulating ATP synthesis
236
ATP closes the ____ channel, causing
K+
Depolarization
237
What happens when K+ channel closes in pancreatic beta cell
V-gated Ca+2 channel opens and Ca+2 triggers exocytosis of insulin
238
What inhibits exocytosis of insulin in the pancreatic beta cell
Somatostatin and NE
239
normal fasting blood glucose level:
80-90 mg/100 ml
240
What happens immediately after acute elevation of blood glucose? (After meal)
10x increase in insulin
241
What happens w insulin about 15 min after meal?
Increase due to new insulin synthesis (there is a dip between the 1st and second phase)
242
Most potent amino acids
Arginine and lysine
243
There is a higher response with arginine and lysine than _____ alone, when they are all combined together
Glucose
244
Gastrointestinal hormones that control insulin secretion
Gastric, secretin, cholecytokinin, glucose-dependent insulinotrophic peptide (AKA gastric inhibitory peptide)
245
Gastrointestinal hormones cause:
An “anticipatory” increase in blood insulin
246
Other hormones that control insulin secretion
Glucagon
Growth hormone
Cortisol
247
Factors that increase insulin secretion:
```
Increased blood glucose
Increased blood FFA
Increased blood amino acids
Gastrointestinal hormones (gastric, CCK, secretin, GIP)
Glucagon, growth hormone, cortisol
Parasympathetic stimulation (Ach)
Insulin resistance, obesity
```
248
Factors that decrease insulin secretion
```
Deceased blood glucose
Fasting
Somatostatin
Alpha-adrenergic activity (NE)
Leptin
```
249
Type 1 diabetes mellitus
Insulin dependent (IDDM)
Lack of insulin secretion by pancreas
Autoimmune disease against beta cells, viral infections, genetics— there are factors
250
Type II diabetes mellitus
Non-insulin dependent (NIDDM)
| Decreased sensitivity to insulin (insulin resistance)
251
Signs and symptoms of type 1 diabetes
```
Increased blood glucose
Glucose readings
Polyurea
Dehydration
Polydipsia
Polyphagia with weight loss
Blood vessel damage
Peripheral neuropathy
Hypertension/kidney disease
Atherosclerosis
Ketoacidosis (metabolic acidosis)
```
252
Which type of diabetes is more common
Type II- 90-95% more common
253
Type II diabetes usually occurs:
It is often associated with:
After age 30, gradual onset
Obesity
254
Type II insulin levels:
Also comes with:
Increased
Mild hyperglycemia
Beta cell exhaustion
Less problems with ketoacidosis than type 1
255
Diabetes complications:
| Macrovascular:
```
Stroke
Heart disease and hypertension
Peripheral vascular disease
Foot problems
Unstable plaque ruptures
```
256
Microvascular diabetes complications
```
Diabetic eye disease (retinopathy and cataracts)
Renal disease
Neuropathy
Foot problems
Blood clot blocks blood flow
```
257
Hyperinsulin
Too much insulin
258
Causes of too much insulin
Adenoma of islets of langerhans (rare)
Insulin “shock”
259
Insulin shock-
Insulin causes:
Nervous system ____
Excessive drop in plasma glucose
Starves
260
Insulin shock initially leads to:
Then hypoglycemia progresses to:
Hallucinations, tremors, nervousness
Seizures, coma
261
What causes insulin shock?
Too much insulin in the blood due to overdose during an insulin shock
262
Too much insulin results in:
Too little blood glucose
263
What will counteract insulin shock
Immediate intake of sugar
264
Structure of glucagon
Large polypeptide
265
Glucagon is secreted by
Alpha cells of the islets
266
Effects of glucagon:
```
Increase glycogenolysis (liver)
Increased gluconeogenesis (liver)
```
Activated adipose cell lipase
267
How does glucagon stimulate glycogenolysis
Uses adenyl cyclase/cAMP/Protein Kinase A mechanism
PKA activates phosphorylase b kinase into phosphorylase a kinase
Degradation of glycogen into glucose-1-phosphate is promoted
This is then dephosphorylated and glucose is released from liver cells
These steps exhibit “amplification”
268
Gluconeogenesis increases:
Rate of amino acid uptake by liver cells
269
Gluconeogenesis includes conversion of:
Some amino acids into glucose by activating enzymes repsponsible
270
at high levels, glucagon activates:
Adipose cell lipase making fatty acids available to the body
271
What stimulates glucagon secretion
Hypoglycemia
Autonomic activation
Increased plasma amino acids (aa would increase insulin production, however in the case of glucagon, the amino acids are used for gluconeogenesis)
272
Inhibition of glucagon secretion
Hyperglycemia
Insulin
Somatostatin
273
Structure of somatostatin
Polypeptide
274
Somatostatin is secreted by
Delta cells
275
Effects of somatostatin
Depresses insulin and glucagon secretion
Decreases stomach motility, GI absorption
Extends time over which food is assimilated into tissues
276
Somatostatin is AKA as
The growth hormone inhibitory hormone from the hypothalamus
277
Stimulation of somatostatin increases:
```
Plasma glucose, amino acid, and FA levels
GI hormones (gastric, secretin, cholecytokinin, GIP)
```
278
Inhibition of somatostatin
Decreased plasma glucose, amino acid, FA levels
279
What are the two enzymes involved in catecholamines degradation?
MAO
| COMT
280
Insulin and glucagon levels for glycogen synthesis
Insulin increases
| Glucagon decreases
281
Insulin and glucagon levels for glycolysis (energy release)
Insulin increases
Glucagon decreases
282
Insulin and glucagon levels for lipogenesis
Insulin increases
Glucagon decreases
283
Insulin and glucagon levels for protein synthesis
Insulin increases
Glucagon decreases
284
Insulin and glucagon levels for glycogenolysis
Insulin decreases
Glucagon increases
285
Insulin and glucagon levels for gluconeogenesis
Insulin decreases
Glucagon increases
286
Insulin and glucagon levels for lypolysis
Insulin decreases
Glucagon increases
287
Insulin and glucagon levels for ketogenesis
Insulin decreases
Glucagon increases
288
Insulin’s effect on:
Blood sugar:
Cell sugar utilization:
Cell fatty acid utilization:
Protein synthesis:
Speed of response:
Bs- decreases
CSU- Increases
CFU- decreases
PS- increases
SOR- Fast
289
GH effects on:
Blood sugar:
Cell sugar utilization:
Cell fatty acid utilization:
Protein synthesis:
Speed of response:
BS- increase
CSU- decrease
CFU- increase
PS- Increase
SOR- slow
290
Glucagon effect on:
Blood sugar:
Cell sugar utilization:
Cell fatty acid utilization:
Protein synthesis:
Speed of response:
BS- increase - with gluconeogenesis
CSU- decrease
CFU- increase
PS- decrease
SOR- fast
291
Epinephrine effect on:
Blood sugar:
Cell sugar utilization:
Cell fatty acid utilization:
Protein synthesis:
Speed of response:
Bs- increase
CSU- increase
CFU- increase
PS- N/A
SOR- fast
292
Cortisol effects on
Blood sugar:
Cell sugar utilization:
Cell fatty acid utilization:
Protein synthesis:
Speed of response:
BS- Increase
CSU- decrease
CFU- increase
PS- decrease (except liver)
SOR- slow
293
Blood Ca+2 and PO4 concentrations depend on: (3)
Intestinal absorption rate
Renal excretion rate
Bone mineral uptake/release
294
Major regulatory factors of Ca+2 and PO4
Parathyroid hormone
Calcitonin
Vitamin D
295
Ca+2 secreting organs
Bone
Kidney
Intestine
296
Important Ca+2 functions
Muscle contraction
Nerve impulse transmission
Blood clotting factor
Bone matrix component
Neurotransmitter release
297
ECF concentration must be:
Tightly controlled
298
Signs of hypocalcemia
Nervous system hyper-excitability
Poor blood clotting
Numbness and tingling
Tetany, spasms
Cardiac arrhythmia
299
Signs of hypercalcemia
Nervous system compression (depression, conduction, lethargy)
Cardiac arrhythmia
Constipation, nausea, vomiting
300
Percentage for normal body calcium distribution for
ECF/plasma
Cells
In bones
ECF- 0.1%
Cells- 1%
Bones- 99%
301
Calcium distribution in plasma
50% ionized calcium
41% protein-bound calcium
9% Ca+2 complexed to anions
302
Phosphate distribution in body
85% in bones
14-15% in cells
< 1% in ECF
303
Depending on _____, phosphate forms:
PH
HPO4^-2
H2PO4^-1
304
Functions of phosphates
Bone matrix
Intracellular buffer
Renal tubular buffer
Phosphorylation (ATP, Enzymes, Etc)
305
Hyper/Hypo phosphatemia
Not generally significant except phosphate depletion may lead to bone demineralization
306
Review picture in slide 102
Slide 102
307
Osteoid in bones give:
Includes:
Tensile strength
Collagen fibers
Ground substance
308
Bone salts give:
| Includes:
Compressive strength
Hydroxyapatite crystals Ca10(PO4)6(OH)2
Non crystalline amorphous substances - CaHPO4.2H2O
- Ca3(PO4)2.3H2O
309
What inhibits HAP deposition in tissues other than bone?
Pyrophasphate
310
Calcification of osteoblasts process
Osteoid is laid down
Osteoblasts become encased and become osteocytes
Precipitation of bone salts in osteoid
Woven bone (new bone) becomes low HAP, high amorphous salts
Replaced by stronger bones (higher HAP)
Some amorphous salts are always there and easily exchanged
311
Formation of osteocyte
Osteogenic cells
To osteoblasts
To osteocytes
312
Osteoclasts secrete
Proteolytic enzymes and acid, which tunnels into bone
- osteoblasts fill in the new bone
313
Calcification and absorption =
Remodeling
314
Review slide 106 for Vitamin D
Slide 106
315
Active form of vitamin D
1/25 dihydroxycholecalciferol
316
Vitamin D promotes
Intestinal calcium absorption (Calcium binding protein)
Phosphate absorption by intestines
317
Vitamin D decreases
Renal calcium and phosphate excretion (minor)
318
Excessive vitamin D leads to
Bone absorption
319
Small amounts of vitamin D leads to
Bone calcification
320
Parathyroid hormone (PTH) without vitamin D leads to
No absorption
321
Anatomy of parathyroid gland
4 small glands located post to the thyroid gland
2 on the left
2 on the right
322
Parathyroid gland-
Chief cells secrete:
Oxyphil cells:
PTH
Function of oxyphil cells is unknown
323
PTH target tissues
Bone- cAMP dependant
Kidneys- cAMP dependant
Intestines- indirectly due to PTH effects on vitamin D
324
PTH increases:
| How?
Blood CA+2 levels
| Mainly by bone absorption
325
PTH decreases:
How?
Blood phosphate levels
Mainly by increase excretion by kidneys
326
What inhibits PTH release
Rising Ca+2 in blood
| Calcitonin, Vitamin D
327
PTH activates:
Osteoclasts- calcium and phosphate ions release in the blood as a result.
328
Specific effect PTH has on intestines
Increases the calcium and phosphate absorption from food (bc of increased vitamin D)
329
How does PTH affect the kidneys
Promotes activation of vitamin D
Decreases calcium excretion
Increases phosphate excretion (which overrides increased phosphate absorption from bone)
Occurs mainly in the distal tubules collect tubules
330
2 phases of bone absorption by PTH:
Rapid phase (osteolysis)
Slow phase
331
Rapid phase of bone absorption is mediated by:
It causes:
Osteocytes and osteoblasts (have PTH receptors)
Causes release of calcium and phosphorus salts
332
Slow phase of absorption is mediated by:
It breaks down:
Osteoclasts activated indirectly by osteocytes and osteoblasts. This stimulate osteoclasts and increase development of new osteoclasts
Breaks down osteoid as well as minerals
333
PTH is stimulated by:
Decreased ECF Ca+2, histamine, epinephrine
334
PTH is released in a ______ pattern
Diurnal
335
What happens with hypoparathyroidism
Calcium reabsorption from bones is depressed
336
What happens to ECF Ca+2 levels with hypoparathyroidism
It decreases (hypocalcemia)
337
Hypoparathyroidism results in
Tentany
338
Signs of hypoparathyroid
Muscle spasm of hands and feet
339
Potential causes of hypoparathyroidism
Autoimmune disorder
Thyroid surgery complication
Genetic
340
Peptide released by parafollicular cells of the thyroid gland
Calcitonin
341
Calcitonin target tissue
Bone
342
Effects of calcitonin
Decrease in:
Osteoclasts activity
Osteocytic osteolysis
Formation of new osteoclasts
343
Prolonged decrease in osteoclasts activity leads to:
Therefore:
Decreased osteoblast activity
No appreciable changes in calcium ion concentration
—there is a very weak effect on kidney to increase calcium excretion
344
Hyperparathyroidism causes extreme:
Osteoclastic activity
345
Hyperparathyroidism increases:
ECF Ca+2 levels (hypercalcemia)
346
Hyperparathyroidism causes decreased:
Phosphate levels
347
Hyperparathyroidism and its effect on bones
It weakens bones with frequent fractures
Cystic bone “osteitis fibrosa cystica”
348
Hyperparathyroidism causes high:
Plasma alkaline phosphate seems
349
Hyperparathyroidism causes depression of:
Nervous system, muscle weakness and constipation
350
Hyperparathyroidism causes metastic:
Calcification
And kidney stones
351
Primary causes of Hyperparathyroidism
Tumor
Autoimmune disease
352
Secondary causes of Hyperparathyroidism
Vitamin D deficiency\
353
Vitamin D deficiency leads to
Hypocalcemia and hypersecretion of PTH
(Rickets- child)
(Osteomalacia- adult)
354
Types of physiological alkaline phosphatase (ALP)
Infancy
Puberty
Pregnancy
Intestinal isoenzymes
355
Bone diseases that cause increase serum alkaline phosphatase enzyme activity
Hyperparathyroidism
Osteomalacia, rickets
Paget’s disease of bone
Osteomyelitis
356
Hepatobiliary diseases that cause increase serum alkaline phosphatase enzyme activity
Hepatitis
Cholestasis
Cirrhosis
357
Another cause of alkaline phosphatase
Carcinoma of the bronchus
358
Effects of rickets
Short stature (stunted growth)
Odd-shaped skull
Spine deformities
Pigeon chest
Odd-shaped ribs
Pelvic Deformities
Wide wrist joints
Wide knee joints
Bowlegs
Wide ankle joints
