Lecture 78 Flashcards
1
Q
There are two copies of the adrenal gland, they lie at:
A
The superior poles of two kidneys
2
Q
There are __ copies of the adrenal gland
A
two
3
Q
each adrenal gland has __ distinct parts
A
two distinct parts
4
Q
The central part of adrenal gland
A
Adrenal medulla
5
Q
Adrenal medulla is regulated by :
A
The sympathetic nervous system
6
Q
Major secretion of the adrenal medulla:
A
epinephrine (E)
7
Q
minor secretion of the adrenal medulla:
A
norepinephrine
8
Q
How many zones does the adrenal cortex have?
A
3
9
Q
What are the three zones of the adrenal cortex;
A
(1) Zona reticularis (inner layer)
(2) Zona fasciculata (middle layer)
(3) Zona glomerulosa (outer layer)
10
Q
Inner layer of the adrenal cortex:
A
Zona reticularis
11
Q
Middle layer of the adrenal cortex:
A
Zona fasciculata
12
Q
Outer layer of the adrenal cortex:
A
Zona glomerulosa
13
Q
The adrenal cortex secretes:
A
corticosteroids /adrenocortical hormones
14
Q
The adrenal cortex secretes corticosteroids which include more than __ types of hormoens
A
30
15
Q
Corticosteroids are synthesized from :
A
cholesterol
16
Q
corticosteroids are grouped into (3):
A
(1) mineralocorticoids
(2) glucocorticoids
(3) androgens
17
Q
Principal mineralcorticoid
A
Aldosterone
18
Q
Mineralocorticoids secreted from which part of the adrenal cortex:
A
outer layer ( zona glomerulosa)
19
Q
Mineralocorticoids affect:
A
electrolytes Na, K ions in extracellular fluid
20
Q
Mineralocorticoids can also have a weak __ effect (asides from their own effect)
A
Glucocorticoid effect
21
Q
What is the principal glucocorticoid
A
Cortisol
22
Q
What is the main function of glucocorticoids ?
A
increase glucose concentration in the blood
23
Q
Aside from their primary function, glucocorticoids can also have a :
A
weak mineralcorticoid effect
24
Q
Glucocorticoids secreted from which parts of the adrenal cortex (2) :
A
(1) Middle layer (zona fasciculata )
(2) inner layer (zona reticularis )
25
The adrenal cortex secretes corticosteroids (mineralocorticoids, glucocorticoids, androgens), which type of corticosteroids is secreted in smaller amounts:
Androgens
26
Which type of corticosteroid are sex hormones but play a minimal role as compared to estrogen and testosterone?
Androgens
27
Androgens are secreted from which layer of the adrenal cortex:
(1) middle layer adrenal cortex (zona fasculata)
(2) inner layer (zona reticularis)
28
which type of corticosteroid has similar effects on body as testosterone:
Androgens
29
All the adrenocortical hormones are __ based hormones
steroid-based compounds
30
All the adrenocortical hormones are steroid-based compounds, they are formed mainly from
cholesterol
31
Low-density lipoprotein (LDL) in blood contains:
cholesterol
32
LDL-cholesterol is absorbed from blood by
endocytosis through cell membrane
33
LDL-cholesterol is absorbed from ___ by endocytosis through cell membrane
blood
34
The cell membrane of adrenal cortex promotes
endocytosis
35
Aside from uptake from blood, how else is cholesterol made available to adrenal cortical cells?
Precursor: Acetyl-CoA
Process: Cortical cells can produce small amounts of cholesterol internally through a multistep biosynthetic pathway starting from acetyl-CoA.
36
Cholesterol becomes ___ , __ becomes __, which is a precursor to many hormones
* Cholesterol becomes pregnenolone, pregnenolone becomes progesterone, which is a precursor to many hormones.
37
Major steps in the synthesis of adrenocortical hormones (4):
Cholesterol -> Pregnenolone -> Progesterone -> Aldosterone / Cortisol / Androgen
38
The transport of adrenocortical hormones:
Since they are hydrophobic they rely on carrier proteins to get them around the circulation to their target tissues and get into the extracellular fluid around the cells
39
adrenocortical hormones are hydrophobic or hydrophilic:
hydrophobic
40
(The transport of adrenocortical hormones) Up to 94% of cortisol binds with
globulin
41
Globulin also known as (2):
(1) cortisol-binding globulin (2) transcortin
42
(The transport of adrenocortical hormones): about 6% of cortisol is :
'floating' freely in blood
43
(The transport of adrenocortical hormones) what do we mean by dynamic equilibrium in regards to cortisol
The cortisol is jumping on and off the carrier (globulin), but most of it (94%) is on the carrier at any given time
44
(The transport of adrenocortical hormones): Up to 50% of __ binds with plasma proteins
aldosterone
45
(The transport of adrenocortical hormones): Up to 50% of aldosterone binds with:
plasma proteins
46
(The transport of adrenocortical hormones): Up to 50% of aldosterone binds with plasma proteins, with the remainder ___
Floating freely in blood
47
(The transport of adrenocortical hormones):is aldosterone in a dynamic equilibrium?
Yes, but only half is on the carrier (plasma proteins) at any time
48
What is the mineralocorticoid function of aldosterone?
Primarily to regulate the balance of sodium (Na⁺) and potassium (K⁺) ions in the body, which in turn influences water balance and blood pressure.
49
Aldosterone promotes transport of Na+ and K+ through
renal tubular walls and in the cortex and collecting ducts
50
Aldosterone acts on __ cells
principle cells
51
Aldosterone increases
the reabsorption of Na+ from the filtrate which means that Na+ is conserved in extracellular fluid (reduces sodium loss in urine)
52
Aldosterone decreases:
the loss of Na+ into urine
53
When sodium is reabsorbed due to aldosterone it increases __ and also causes__
When sodium is reabsorbed it increases the excretion of K+ into urine and also causes water to be reabsorbed by osmosis
54
what are some important substances regulated by the kidney (6)
Na+
K+
Cl-
Ca2+
glucose
phosphate
55
The cellular mechanism of aldosterone action that increases sodium reabsorption is explained by the following cascade:
The lipid soluble aldosterone can diffuse readily into the principal epithelial cells, -> binds with a receptor in the tubular cell, diffuses into the nucleus, -> Causes the formation Channel proteins and Na-K ATPase pump -> now Na+ can be reabsorbed, K+ excreted.
56
mineralocorticoid function of aldosterone: channel proteins are inserted into
luminal membrane of principal cell
57
mineralocorticoid function of aldosterone: Channel proteins are inserted into luminal membrane of principal cell and result in
rapid diffusion of Na+ from lumen side, into cell cytoplasm
58
The luminal side of the kidney is the side:
pointing inwards, where the kidney filtrate (urine) is located
59
mineralocorticoid function of aldosterone:Na/K ATPase enzyme works together with __ to pump Na+ and K+ at the basolateral membrane of renal principal cells
Membrane transport proteins
60
Na/K ATPase enzyme works together with membrane transport proteins to:
Pump Na+ and K+ at the basolateral membrane of renal principal cells.
61
Basolateral membrane is
the side of the tubule cell that faces outwards, to the interstitial fluid
62
The interstitial fluid is connected to
the blood circulation
63
The cortex, outer medulla and inner medulla refers to parts of the
kidney, not adrenal glands
64
renal epithelial cells make up the walls of:
the tubules
65
renal principal epithelial cells make up the tubules are are in (2):
the cortex and collecting ducts
66
Aldosterone causes Na+ to be conserved -> tendency of increasing concentration of sodium -> simultaneous __
osmotic absorption of water by principal cells -> keep the concentration of Na+ constant ( very little rise ) in extracellular fluid -> absorption of water increases the volume of extracellular fluid -> increase blood pressure -> cause great increase of excretion of both water and salt (sodium chloride) from kidney at hypertension ( called pressure diuresis ).
67
Aldosterone increase reabsorption of __ and secretion of __
Aldosterone increase reabsorption of NaCl and secretion of K+
68
Aldosterone increase reabsorption of NaCl and secretion of K+ by __ cells
principal cells
69
Effects on sweat gland, salivary gland and intestinal absorption: Aldosterone increase reabsorption of NaCl and secretion of K+ by principal cells to :
conserve body salt when water is secreted by sweat gland and salivary gland
70
Effects on sweat gland, salivary gland and intestinal absorption; Aldosterone enhance NaCl absorption from __, especially in __ to ___
intestine especially in the colon to prevent salt loss in the stools.
71
Effects on sweat gland, salivary gland and intestinal absorption: Enhance NaCl absorption by intestine especially in the colon to:
prevent salt loss in the stools.
72
Lack of Aldosterone causes:
loss of Na+ in urine (no reuptake) -> decrease sodium-chloride in extracellular fluid and the volume of fluid -> great reduction of total volume of extracellular fluid (dehydration) and diminished cardiac output -> low blood pressure -> circulatory shock --> cause death in few days.
73
If aldosterone is chronically low or defective due to a genetic mutation, it can be fatal. It can be prevented by providing
medicine including aldosterone or other mineralocorticoids. It is an acute life-saver.
74
If aldosterone is not working, it can cause gradual increase of
K+ concentration in extracellular fluid and blood that is far above the normal which causes serious cardiac toxicity
75
If aldosterone is not working, it can cause gradual increase of K+ concentration in extracellular fluid and blood that is far above the normal which causes:
serious cardiac toxicity
76
hyperkalemia symptoms include (2):
(1) weakness of heart contraction
(2) arrhythmia (irregular heart beat)
77
When K+ concentration reaches to 60 to 100% above normal (aldosterone not functioning) it is a condition termed:
hyperkalemia
78
excess aldosterone causes
massive retention of Na+ and water reabsorption, which increases blood pressure and may trigger pressure diaresis
79
hypokalemia:
causes excessive loss of K+ from extracellular fluid which can lead to a serious decrease of K+ concentration in blood (excessive aldosterone)
80
When K+ concentration fall below 1/2 to 1/3 normal it prevents _ :
Transmission of normal action potential in the nerve which develops severe muscle weakness (hypokalemia)
81
Aldosterone secretion is regulated by at least:
four factors
82
Aldosterone secretion is regulated by at least four factors, listed in order of relative importance:
1. A small increase of K+ concentration in extracellular fluid will increase aldosterone secretion.
2. An increase of activity of renin-angiotensin system will increase aldosterone secretion
3a. An increase of Na+ concentration in extracellular fluid decreases aldosterone secretion.
3b. A 10 to 20% decrease of Na ion concentration can double aldosterone secretion.
4. When adrenocoticotropic hormone (ACTH) is secreted from anterior pituitary it causes aldosterone secretion. This is the most minor factor, however, if there is a total absence of ACTH, like a genetic disease, it can significantly reduce aldosterone secretion.
83
A small increase of K+ concentration in extracellular fluid will increase/decrease aldosterone secretion.
increase
84
An increase of activity of renin-angiotensin system will increase/decrease aldosterone secretion
increase
85
An increase of Na+ concentration in extracellular fluid increases/decreases aldosterone secretion.
decreases
86
A 10 to 20% decrease of Na ion concentration can
double aldosterone secretion
87
When adrenocoticotropic hormone (ACTH) is secreted from anterior pituitary it causes
aldosterone secretion
88
When adrenocoticotropic hormone (ACTH) is secreted from __ it causes aldosterone secretion
anterior pituitary
89
if there is a total absence of ACTH, like a genetic disease, it can
significantly reduce aldosterone secretion.
90
What is the effect of cortisol on carbohydrate metabolism?
Cortisol stimulates gluconeogenesis
91
gluconeogenesis is:
the formation of glucose from amino acids and other substances by liver
92
Cortisol, a glucocorticoid hormone plays a major role in
increasing blood glucose levels by stimulating gluconeogenesis in the liver.
93
Cortisol can increase the rate of gluconeogenesis by how much?
6 to 10 fold under certain physiological conditions—especially during stress, fasting, or prolonged exercise.
94
cascade of events by which cortisol increases gluconeogenesis:
Cortisol binds with receptor in the cytoplasm of hepatic cells -> diffuses into liver cell nucleus and activates DNA transcription -> formation of messenger RNA -> increase the enzymes needed to convert amino acids into glucose in hepatic (liver) cells.
95
Cortisol mobilizes:
amino acids from muscles
96
Cortisol mobilizes amino acids from muscles. Mobilize means that:
the proteins are digested into amino acids
97
Cortisol mobilizes amino acids from muscles. Mobilize means that the proteins are digested into amino acids. This is a ____ effect
catabolic
98
Cortisol mobilizes amino acids from muscles. Mobilize means that the proteins are digested into amino acids. This is a catabolic effect. The amino acids then:
leave the muscle and are available in the plasma. Amino acids go from plasma to enter into liver for gluconeogenesis.
99
Cortisol causes a moderate decrease in
the utilization of glucose by cells
100
Cortisol causes a moderate decrease in the utilization of glucose by cells. This is because (2):
(1) cortisol antagonizes insulin
(2) cortisol depresses the oxidation of nicotinamide-adenine dinucleotide (NADH) to form NAD+ and H (Those must be oxidized to allow the use of glucose by cells for aerobic metabolism. Thus, anaerobic metabolism and aerobic metabolism are attenuated, the cells can not effectively use glucose for energy)
101
If cortisol is in excess for long time
the glucose will accumulate in the blood and can be 50% more above normal
102
adrenal diabetes
If cortisol is in excess for long time, the glucose will accumulate in the blood and can be 50% more above normal
103
Cortisol works on the body to
produce and conserve carbohydrates
104
Cortisol works on the body to produce and conserve carbohydrates. This allows the body to have
have carbohydrate reserves, which can be used if epinephrine or glucagon are present.
105
What is the effect of cortisol on protein metabolism?
* Cortisol reduces the protein stores in all body cell due to catabolic effects.
106
Cortisol prevents amino acids from
entering extra-hepatic cells (all the non-liver cells).
107
Cortisol reduces the protein stores in all body cell due to catabolic effects, except:
protein will increase in the liver
108
Cortisol reduces the protein stores in all body cell due to catabolic effects, exceptprotein will increase in the liver because:
cortisol promotes uptake of amino acids into liver for gluconeogeneis
109
cortisol promotes
large amounts of liver enzymes that are needed for gluconeogenesis.
110
most proteins in muscles and other tissues are decreased by cortisol except for
liver proteins which are increased.
111
What is the effect of cortisol on fat metabolism?
Cortisol promotes mobilization of fatty acids from adipose tissue
112
describe pathway: Cortisol promotes mobilization of fatty acids from adipose tissue
The triglycerides are digested into free fatty acids and glycerol -> increases the concentration of free fatty acids in plasma -> increases oxidation of fatty acids in cells into acetylCoA -> increases use of fatty acids for metabolic energy ->allows for long-term conservation of body glucose and glycogen
113
Even though cortisol promotes 'fat burning', if there is excessive secretion of cortisol it may
make a person hungry all the time and stimulate food intake. In this case weight gain may be observed if deposition of fat in tissues is greater than the rate of fat burning.
114
An anti-inflammatory effect of cortisol happens when
tissue is damaged by trauma or infection tissue becomes inflamed.
115
The stages of inflammation include (5):
* Chemicals release from the damaged tissue cell and activate inflammation process. The chemicals include histamine, bradykinin, proteolytic enzyme, prostaglandins and leukotrienes.
* Blood flow is increased in the inflamed area (called erythema).
* Large amount of plasma leak out of the capillaries into damaged area because of the increased capillary permeability.
* Leukocytes infiltrate through the area.
* At the end of inflammation, there is growth of fibrous tissue for the healing process.
116
Cortisol has two basic anti-inflammatory effects:
1. It can block (attenuate) the early stage of inflammation
2.If inflammation has already begun, cortisol blocks most of factors that promote inflammation and causes rapid resolution of inflammation, and increases healing rate.
117
Cortisol can block the early stage of inflammation, because
(a) Most of the **proteolytic enzymes that cause inflammation** are stored in lysosomes in the tissue cell. **Cortisol can make the membrane of lysosome cell much more difficult to be ruptured** -> **greatly decrease the release of proteolytic enzymes** into the inflamed area.
(b) Cortisol **decreases the permeability of capillaries because of the reduced release of proteolytic enzyme**s -> reduce loss of plasma into damaged tissue area.
(c) Cortisol** decreases the mobility of white blood cell into inflamed area ** -> **decrease phagocytosis of the damaged tissues.**
(d) R**educe the release of interleukin-1 from white blood cel**l -> **suppresses the hypothalamic temperature control system** -> lower the fever
118
If inflammation has already begun, cortisol blocks most of factors that promote inflammation and causes rapid resolution of inflammation, and increases healing rate. How?
a) Cortisol causes mobilization of amino acids and promote the use of them to repair damaged tissues, to increase glucose and fatty acids for cellular energy.
b) Plays an important role in combating rheumatoid arthritis, rheumatic fever, and acute glomerulonephritis.
119
Besides the two main basic anti anflamatory effects of cortisol, what are three other effects?
* Cortisol reduces allergic reaction by reducing inflammation and the release of inflammatory products.
* Decrease the release of lymphocytes and antibodies from lymphoid tissue -> immunity of body is suppressed -> makes cortisol and other glucocorticoids to be the most useful drugs for preventing immunological rejection of transplanted heart, kidney and other tissues.
* Increase production of red blood cells and promote healing of tissues
120
Secretion of cortisol is primarily regulated by
ACTH (corticotropin or adrenocorticotropin hormone)
121
Secretion of cortisol is primarily regulated by ACTH (corticotropin or adrenocorticotropin hormone) which is secreted by
anterior pituitary gland
122
Secretion of cortisol is primarily regulated by ACTH (corticotropin or adrenocorticotropin hormone) which is secreted by anterior pituitary gland in response to
to corticotropin releasing hormone (CRH), also known as corticotropin releasing factor.
123
The neurons of hypothalamus release corticotropin realeasing hormone (CRH) through hypophysial portal system in median eminence to anterior pituitary, which causes
secretion of ACTH from anterior pituitary
124
adrenocorticotropin hormone (ACTH) acts on the adrenal cortex to:
synthesize adrenocortical hormones and cause them to be secreted.
125
Pain stimuli resulted from physical stress or tissue damage can be transmitted to brain stem -> then to hypothalamus, by this cascade:
Cause release of corticotropin releasing hormone (CRH) to hypophysial portal system --> release of ACTH from anterior pituitary into blood -> (adrenocorticotropin hormone) ACTH to adrenal cortex -> release of cortisol -> increase concentration of cortisol
126
Cortisol has a __ feedback effect on the hypothalamus to ___ of CRH
Cortisol has a direct negative feedback effect on the hypothalamus to decrease formation of CRH
127
Cortisol also has a __ feedback on the anterior pituitary gland to ___ of ACTH.
Cortisol also has a direct negative feedback on the anterior pituitary gland to decrease the formation of ACTH.
128
Cortisol has a direct negative feedback effect on (2):
(1) hypothalamus to decrease formation of corticotropin releasing hormone (CRH)
(2) anterior pituitary gland to decrease the formation of ACTH (corticotropin or adrenocorticotropin hormone)
129
Different types of stress can cause immediate increase in __ secretion by ___
Different types of stress can cause immediate increase in ACTH secretion by anterior pituitary gland
130
Different types of stress can cause immediate increase in ACTH secretion by anterior pituitary gland, which, in turn;
increases the secretion rate of cortisol by adrenal cortex
131
Addison's disease is a type of __adrenalism:
hypoadrenalism
132
There is a condition called hypoadrenalism (for example Addison's disease) which is a
primary adrenal insufficiency
133
There is a condition called hypoadrenalism (for example Addison's disease) which is a primary adrenal insufficiency. It is primary because
the adrenal gland does not make enough of the adrenal hormones (cortisol and aldosterone)
134
Secondary adrenal insufficiency occurs when
the pituitary gland doesn't make enough of the hormone ACTH. The adrenal glands then don't make enough cortisol.
135
what is more common between primary (Addison's) and secondary adrenal insufficiency?
secondary adrenal insufficiency
136
causes second adrenal insufficiency (5)?
(1) Genetic mutation
(2) birth defect
(3) infection of the pituitary
(4) problem with hypothalamus (or CRH)
137
If the primary or secondary adrenal insufficiencies are chronic, they can have the following effects depending on which hormones are missing:
If there is a lack of mineralcorticoids such as aldosterone:
The sodium ions are excreted into urine, which causes loss of water by osmosis. If its untreated blood pressure and dehydration can be fatal. Also, there is compensatory increase in potassium in the blood that can lead to hyperkalemia.
138
If the primary or secondary adrenal insufficiencies are chronic, they can have the following effects depending on which hormones are missing:* If there is a lack of glucocorticoids such as cortisol
Then in between it is difficult to maintain blood glucose levels since gluconeogenesis is impaired. Stress of infection can be deadly because cortisol normally suppresses inflammation and promotes healing.
139
If the primary or secondary adrenal insufficiencies are chronic, they can have the following effects depending on which hormones are missing: If the medulla is defective, then
the lack of catecholamines such as adrenaline will alter mood and make hypoglycemia more likely. Adrenaline is able to mobilize glucose in times of need, so lacking it is dangerous.
140
The adrenal medulla is the inner region of the adrenal gland and is responsible for producing:
catecholamines, primarily adrenaline (epinephrine) and noradrenaline (norepinephrine).
141
If the primary or secondary adrenal insufficiencies are chronic, they can have the following effects depending on which hormones are missing: if cortisol is low and high ACTH:
* Melanin deposition is increased. Melanin has various functions including skin pigmentation. Because cortisol is low, the pituitary over produces ACTH, which also provides more MSH (melanin stimulating hormone) which gets unevenly distributed in skin, creating a spotty appearance in the skin. This would not occur if the patient has an ACTH deficiency.
142
There are various treatments for adrenal insufficiency (4)
(1) Daily supplement with synthetic mineralcorticoids and glucocorticoids
(2) In cases of trauma, extra glucocorticoids must be given
(3) Corticosteroids given to suppress the immune system if it is autoimmune in nature
(4) allergic reactions may need more medication to control inflammation
143
There are various treatments for adrenal insufficiency: In cases of trauma; extra __ must be given
glucocorticoids
144
There are various treatments for adrenal insufficiency: __given to suppress the immune system if it is autoimmune in nature
Corticosteroids
145
examples of hyperadrenalism:
(1) Cushing's Syndrome
(2) Conn's syndrome)
146
hyperadrenalism is defined by:
hypersecretion of adrenal hormones
147
hyperadrenalism cause may be (3):
(1) Adenoma tumor which produces adrenal hormones out of control.
(2) in glands or elsewhere in body
(3) an abnormal function of the hypothalamus-pituitary axis that makes more ACTH than needed.
148
In the adrenal excess (hyperadrenalism) diseases, too much of hormone has the following effects: Excessive Glucocorticoids (cortisol) (3):
(1) high blood sugar leading to pituitary diabetes
(2) loss of protein from muscle
(3) redistribution of fat into the torso
149
In the adrenal excess diseases, too much of hormone has the following effects: excessive Androgens
over masculinizing effects
150
The treatment for hyperadrenalism is to:
try and remove or destroy the tumour
151
The treatment for hyperadrenalism: medications can include:
drugs that block steroid hormone synthesis, or drugs that block the effect of the hormones.
152
The treatment for hyperadrenalism: medication:
can include drugs that block steroid hormone synthesis, or drugs that block the effect of the hormones.
