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Endocrine 3
Endocrine 3
Endocrine 3
1
Calcium Homeostasis
• Normal plasma Ca2+ = 9.4 mg/dl
• Importance of Ca2+ in the body
Muscle contraction, Blood clotting
Bone and teeth formation
As a cofactor of enzyme activation
Synaptic transmission
• Hormones involved in calcium homeostasis: PTH,
GH, Calcitriol, Calcitonin etc.
2
Phosphorus Homeostasis
• Found in ATP, cAMP, 2,3-diphosphoglycerate
3
Parathyroid Glands
• There are two major types of cells that make up
parathyroid tissue:
• Histology: 2 cells
2. Oxyphil cell
Unknown function
4
Parathyroid Glands
• Function
• Target tissues(three)
Bone
Kidney
Gut
5
Parathroid Hormone...
Effect of PTH on Bone
• Stimulates osteoclasts (bone resorption)
7
Regulation of PTH secretion
8
Parathyroid disorders
• Hyperparathyroidism: Rare
Calcium is leached from bones & replaced by
connective tissue
Elevated blood Ca2+ adversely affects NS &
contributes to formation of kidney stones as
excess Ca2+ is deposited in kidney tubules
• Hypoparathyroidism: PTH deficiency following injury or
surgical removal
Increased NS excitability
9
7-Dehydrocholestrol
Sun light
3- Cholecalciferol (Vit-D3)
Liver enzyme 25-α Hydroxylase
25-Hydroxycholecalciferol
Kidneys proximal 1 α-Hydroxylase
tubules Stimulated by PTH
1, 25-(OH)2 D3(vitamin D3)
↑ Synthesis of Ca-binding proteins
↑Ca absorption in GIT
10
↑Ca reabsorption in renal tubules
11
Vitamin D
• Role of 1, 25 (OH)2 D3
↑Absorption of Ca in intestine
12
Vitamin D
Calcitonin
• Secreted by thyroid gland,
• Stimulate Ca2+ deposition in bones and secretion by
kidneys, so lowers blood Ca2+
14
Calcitonin
15
Calcitonin...
Effect on bone
• ↓activities of osteoclasts
• ↓formation of new osteoclasts
• ↑activities of osteoblasts
Effect on renal tubules: ↓Reabsorption of
calcium
Effect on GIT: ↓Absorption and transport of
calcium
16
Clinical correlates
Hypocalcemia
• Tetany: Carpopedal spasm: -
Trousseau’s sign
• Chvostek’s sign
• Convulsion
• Laryngismus
• Impaired blood clotting
Hyperventilation Carpal spasm
17
Effect of hormone on phosphorous regulation
18
Effects of Other Hormones on Calcium Metabolism
• GH
• Insulin
• Thyroid hormone
• Estrogen
• Glucocorticoid
19
Summary of Ca-homeostasis
PTH secretion is directly proportional. to blood phosphate level inversely
proportional to blood calcium level
20
Summary of Ca-homeostasis…
21
Adrenal glands
• Located at top of each kidneys
Suprarenal glands
• Weight of each glands:4gm
• Consists of two components
1. Adrenal cortex: Outer part
80% of adrenal gland
2. Adrenal medulla: Inner part (20%)
22
Adrenal cortex
• Adrenal cortex produces steroid hormones
More than 30 steroid hormones
• Have three distinct functional layers
1. Zona glomerulosa:
15% of adrenal cortex
Produces aldosterone due to the presence of
aldosterone synthase
Stimulated by Angiotensin II and potassium in
plasma
23
Adrenal cortex…
2. Zona fasciculata:
• 75% adrenal cortex
• Produces
corticosterone, cortisol
& few adrenal
androgens
• Controlled by ACTH
24
Fig. Stimulation of steroidogenesis by
ACTH in zona fasciculata cells
25
Adrenal cortex…
3. Zona reticularis: inner most zone
Secretes dehydroepiandrosterone (DHEA)
and androstenedione,
Small amounts of estrogens and
Some glucocorticoids
Controlled by ACTH and cortical androgen
stimulating hormone
26
Adrenocortical Hormones synthesis
27
Adrenocortical Hormones
28
Hormones of adrenal cortex
29
Mineralocorticoids: Aldosterone
32
Synthesis of aldosterone
33
Aldosterone secretions control
34
Receptor of Aldesterone
36
Functions of aldosterone…
38
Aldosterone escape
• Escape of the kidney from salt-retaining effects of
excess administration or secretion of aldosterone
• When aldosterone level increases
increases the volume of ECF and
blood pressure.
Aldosterone-induced high blood pressure decreases
the ECF volume through two types of reactions:
• It stimulates secretion of atrial natriuretic
• Peptide (ANP) from atrial muscles of the heart:
39
Aldosterone escape
40
Aldosterone escape
41
Glucocorticoids
43
Cortisol
• 95% activities of glucocorticoids
• Metabolized in liver
1. Metabolic Effects
a. On carbohydrates
Gluconeogenesis hence ↑BGC
b. On protein metabolism
↑Catabolism & decreases anabolism
48
d. On Mineral metabolism(aldosterone like effect)
Na+ reabsorption
K+ excretion
Ca2+ excretion
49
2. Anti-inflammatory effect
Important in Resisting Inflammation
It has anti-inflammatory effects
The administration of large amounts of cortisol can usually
block inflammation.
51
Physiologic effects of cortisol…
5. Anti-allergic action
6. Growth inhibitory effect
↓GH secretion
Activates osteoclasts- bone resorption
Inhibits osteoblasts
Inhibits protein synthesis
52
Physiologic effects of cortisol…
Corticotrops + Pyrogens
Hypoglycemia
_ Histamine
ACh
ACTH
+
Adrenal cortex
Zona fasciculata
↑↑ Cortisol:
54
Effects of stress on a body
Stress
Nerve Hypothalamus
Spinal cord
signals
(cross section) Releasing
hormone
Nerve
cell
Anterior pituitary
Blood vessel
Nerve cell
ACTH
Adrenal
gland
Kidney
56
Adrenal cortex disorder…
Causes of adrenal hypo secretion:
1. Adrenal dysgenesis
gene mutation on ACTH/the cell hypoplasia.
2. Adrenal destruction
Autoimmune destruction of the adrenal cortex.
3. Impaired steroidogenesis
Synthesis problems (cholesterol, enzymes).
57
Adrenal cortex disorder…
59
Adrenal cortex disorder…
Symptoms of Cushing's syndrome:
• Deposition of fat around thoracic & upper abdomen, fat
move from lower part of the body & increased deposition
(the feature is called buffalo torso).
• Other symptoms:
– Face edematous, acne & hirsutism
– Hypertension (as its mineralocorticoid effect)
– Weight gain, particularly of the trunk & face with sparing of the
limbs (central obesity)
– Moon face.
60
Symptoms of Cushing's syndrome
C. Hyper aldosteronism
High aldosteron secretion.
Types
1. 1o (Conn syndrome): tumor of ZG
2. 2o Hyperaldosteronism
Signs, symptoms
hypokalemia, hypernatremia
muscle cramps (due to hyper excitability of neurons),
metabolic alkalosis (due to ↑secretion of H+ by kidney)
High pH of the blood makes calcium less available to the
tissues & causes symptoms of hypocalcaemia.
62
Adrenal androgens
• Produced in small amount mainly at Zona
Reticularis
• Dehydroepiandrosterone (DHEA) &
androstendione
• Both are converted to testosterone in
circulation
• Androgens can be converted to estrogens in
• adipose
Androgenstissue byTestosterone
the aromatase enzyme
Estrogen
Aromatase
63
Adrenal androgens…
• Progesterone is formed in adrenal cortex as
intermediate but not normally released to blood
• Adrenal androgen secretion is primarily controlled by
ACTH
Function of adrenal androgen
• Initiate development of 2o sexual characteristics; enlargement
of genital organs, growth of hairs in axillary and pubic areas
64
Adrenogenital Syndrome
• Hypersecretion of adrenal androgens usually due to
adrenal tumors
• Lead to intense masculinizing effects throughout the
body
• In females: Virilism like beard, deeper voice,
baldness if she has genetic trait for baldness,
masculine hair distribution on body & pubis,
clitoral growth to resemble penis & muscular
65
Adrenogenital Syndrome…
• In males:
Same as characteristics developed in
females
Rapid growth of male sexual organs
66
Catecholamines
• Epinephrine and Norepinephrine
Sympathoadrenal system
• Their
67 receptors are at cell membrane
Synthesis of catecholamines
68
Adrenal Medulla
74
Glucose homeostasis
75
Insulin
80 188
81
Insulin…
82 189
MOA of Insulin
• Insulin binds to its receptor
• Enzyme-linked receptor
• Autophosphorylation of beta subunits activates
tyrosine kinase
• TK then activates insulin receptor substrates
83 190
MOA of Insulin…
84 191
Function of insulin
• Glucose transporter
• Glukokinase
• Liver phosphorylase
• Lipoprotein lipase
• Hormone-sensitive lipase
85 192
Function of insulin
• Muscle
Increased glucose entry
Increased glycogen synthesis
Increased amino acid uptake
Increased protein synthesis in ribosomes
Decreased protein catabolism
Decreased release of gluconeogenic amino acids
Increased ketone uptake
Increased K+ uptake
86 194
Function of insulin
Liver
Decreased ketogenesis
Increased protein synthesis
Increased lipid synthesis
Decreased glucose output due to decreased
gluconeogenesis, increased glycogen synthesis, and
increased glycolysis
General
Increased cell growth
87 195
Functions of Insulin
On CHO Metabolism
• ↑Glucose transport & utilization
• GLUT4(insulin dependent)
88 196
Functions of Insulin
89 197
Functions of Insulin…
• On fat metabolism
↑Lipogenesis, ↓Lipolysis
Inhibits the action of lipase
On ions
↑K+ transport into cells
On growth: Promotes body growth
90 198
Regulation of insulin secretion
Exercise
GIT hormones
Hyperglycemia + • GIP
+ • GLP-1
Amino acids +
• Gastrin
FFA + • Secretin
ketones Factors
• CCK
affecting insulin
Parasympathetic +
Secretion of
Stimulation -
β-cells
– Paracrine
- • Somatostatin
• Sympatheti +
Ach +
c + Oral hypoglycemic drugs
Stimulation (glyburide, tolbutamide)
(ɑ-2 AR ) Hyperkalemia
• Stress GH, PRL Glucagon
91 199
Glucagon
92
How does glucagon work?
1. On CHO metabolism
↑Glycogenolysis, ↑Gluconeogenesis
2. On Lipid metabolism
↑Lipolysis,↑Ketogenesis
On CVS
↑Frequency of heart beat (HR)
↑Cardiac force pf contraction by
activating myocardiac adenyly cyclase
96
Regulation of glucose
• Insulin
• Glucagon
• Sympathetic activity
• Growth hormone
• Glucocorticoids
97
The Regulation of Blood Glucose Concentrations
98
Glucose homeostasis disorders
= abnormalities on insulin.
Diabetes mellitus
Syndrome characterized by hyperglycemia.
Symptoms :
Polyuria
excessive urine production, glucose osmotic effect.
Polydipsia
excessive thirst & ↑ fluid intake, for compensation.
polyphagia
• excessive eating
99
Types of diabetes mellitus
Type I DM Type II DM
• Juvenile diabetes • Maturity onset diabetes
• Insulin dependent DM • Insulin resistance DM
• As the pancreas does not • The pancreas does produce
produce sufficient insulin, it enough insulin, but the target
is treated by insulin cells do not respond to it.
injections.
Complications of DM
- Cardiopathy, nephropathy, neuropathy & retinopathy,
gangrene [wound is unhealed].
100
Hyperinsulinism
Caused: Tumor of β-cells in the islets of Langerhans.
Signs and Symptoms
102
Physiology of sex hormones
Estrogen
Progesterone and
Testosterones
103
Testosterone source
Placenta
ovaries and
Thickens skin
3/6/2023
107 213
Testosterone
CNS
Integumentary system
108 214
Testosterone
• Lipoproteins:
↑ VLDL, ↑ LDL, decrease HDL
(cardiac/ coronary problems in men)
109 215
Estrogen
• Secreted Primarily by
110 216
Estrogen function
• Facilitate the growth of the ovarian follicles
Origin:
Ovarian follicles
Corpus luteum (non-pregnant female)
Placenta (pregnant)
Adrenal cortex
Testes
3/6/2023
112 218
Function of progesterone
• On uterus
• Inhibits excitability of myometrium
• Stimulates secretion of thick, alkaline cervical
mucous
• Promote secretory changes in the uterine
endometrium
• On breast
• Stimulates development of secretary cells.
• Stimulates differentiation of ductile system
• Has a thermogenic action
113 219
Hypothalamic-Pituitary ovary axis
3/6/2023
114 220
Hypothalamic-Pituitary-ovary axis…
3/6/2023
115 221