ANATOMI DAN FISIOLOGI

Dr.HIPOFISE DANPurba,
Bernhard Arianto PANKREAS
M.Kes., AIFO
Textbooks
Guyton, A.C & Hall, J.E. 2006. Textbook of Medical Physiology. The
11th edition. Philadelphia: Elsevier-Saunders: 918-930, 961-977.
Brooks, G.A. & Fahey, T.D. 1985. Exercise Physiology. Human
Bioenergetics and Sts Aplications. New York : Mac Millan Publishing
Company: 122-143.
Foss, M.L. & Keteyian, S.J. 1998. Fox’s Physiological Basis for
Exercise and Sport. 4th ed. New York : W.B. Saunders Company:
471-491.
Astrand, P.O. and Rodahl, K. 1986. Textbook of Work Pysiology,
Physiological Bases of Exercise. New York : McGraw—Hill.
Braunwald, Pauci, et al.2008. Harrison's PRINCIPLES OF
INTERNAL MEDICINE. Seventeenth Edition. New York : McGraw—
Hill: Chapter 332, 333, 338.
Kronenberg, and Melmed. 2008. WILLIAMS TEXTBOOK OF
ENDOCRINOLOGY . The 11th edition . Philadelphia: Elsevier-
Saunders: 155-235, 1329-1407.
General Features of the
Endocrine System
1. Endocrine glands are ductless
2. Endocrine glands have a rich supply of blood.
3. Hormones, produced by the endocrine glands are
secreted into the bloodstream.
4. Hormones travel in the blood to target cells close
by or far away from point of secretion.
5. Hormones receptors are specific binding sites on
the target cell.
 Important Definitions

What are hormones?

Hormones are organic chemical messengers produced
and secreted by endocrine cells into the bloodstream.
Hormones regulate, integrate and control a wide range
of physiologic functions.

Silverthorn, Human Physiology, 3rd

edition Figure 6-1&2
What are endocrine glands?
Endocrine glands are ductless glands comprised of endocrine
cells. This means that these glands do not have ducts that lead to
the outside of the body. For example, sweat glands are NOT
endocrine glands (they are instead exocrine glands) because
sweat glands have ducts that lead to the outside surface of your
skin (that’s how the sweat gets out). The fact that endocrine
glands are ductless means that these glands secrete hormones
directly into the blood stream (instead of to the outside of your
body).
What are target cells?
Target cells refer to cells that contain specific
receptors (binding sites) for a particular hormone.
Once a hormone binds to receptors on a target cell, a
series of cellular events unfold that eventually impact
gene expression and protein synthesis.

Silverthorn, Human Physiology, 3rd

edition Figure 6-1&2
 What are hormone receptors?
Hormone receptors are binding sites on the target cell (either
on the surface or in the cytoplasm or nucleus of the target cell)
that are activated only when specific hormones bind to them. If
a hormone does not/cannot bind to it’s receptor, then no
physiologic effect results.

See next slide for a picture of a hormone bound to its receptor

Growth hormone regulates cell growth
by binding to growth hormone
 Steps in Signal Communication

1. Synthesis
2. Release
3. Transport to target cell
4. Signal detection by specific receptor
5. Change in cellular metabolism
6. Signal removal termination cellular response
Hypofunction Hyperfunction
Destruction Tumor
Block Gland
Hyperplasia

Ectopic production
ProH
Iatrogenic
Block
Stimulation Block
Hormon
Degraded Degraded

Antibodies Receptor
antagonist Antibodies

Defect Effector Stimulation

Response
Tissue damage Tissue damage
Target cell
 Clinical Application
Growth Hormone Ups and Downs
• Gigantism - hypersecretion of GH in children

• Acromegaly – hypersecretion of GH in adults

• Dwarfism – hyposecretion of GH in children

Figure shows oversecretion of GH in adulthood as changes occur in the

same person at ages (a) nine, (b) sixteen, (c) thirty-three, and (4) fifty-
two

1111
HYPOTHALAMUS

Master control hypothalamus

Master integrator

infundibulum

PITUITARY GLAND
pituitary gland
AKA = hypophysis
1 cm in diameter
sella turcica in
0,5-1 gr in weight sphenoid bone

Infundibulum
Hypophysis stalk
Sella turcica
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PITUITARY GLAND (HYPOPHYSIS)

Anterior pituitary
(adenohypophysis)
neurohypophyseal bud infundibulum
derived from Rathke’s from hypothalamus

pouch
Invagination of pharyngeal
connected to
epithelium
hypothalamus by
Posterior pituitary portal
hypophyseal
(neurohypophysis)
system bud from roof of mouth
called Rathke’s pouch
A neural tissue outgrowth of neurohypophysis

adenohypophysi
hypothalamus loses connection
s
connected to hypothalamus with mouth cavity

by
nerve tract
contains pituicytes
 Hypophysis or Pituitary Gland

D = pars distalis, I= pars intermedia

N = pars nervosa, S = stem or stalk
T = pars tuberalis

Posterior lobe Anterior lobe

tuitary gland or Hypophysis

Adenohypophysis
Neurohypophysis
Pars distalis or anterior lobe

Pars nervosa
or posterior lobe

Intermedia between black lines

Hormones of the Pituitary
Gland

1818
Hypothalamic
Hormones

1919
Tissues can be targeted by multiple hormones

Hormones can act synergistically, permissively, or

antagonistically

Synergistic effects of
hormones on blood
glucose concentration
 Sensory input from environment

Neuroendocrine Central nervous system

origins of
signals
Hypothalamus

Hypothalamic hormones
(releasing factors)

First target Anterior pituitary Posterior pituitary

Corticotropin Thyrotropin Folicle- Luteinizing Somatotropin Prolactin Oxytocin Vasopressin Blood

(ACTH) Mr28,000 stimulating hormone (growth hormone) Mr22,000 Mr1,007 (antidiuretic glucose
Mr4,500 hormone Mr20,500 Mr21,500 hormone) level
Mr24,000 Mr1,040

Seconds targets Adrenal Thyroid Ovaries/testes Islet cells of Adrenal

cortex pancreas medulla

Cortisol Thyroxine Progesterone, Insulin, Epinephrine

corticosterone, (T4), triiodo extradiol glucogen,
aldosterone thyronine (T3) Testosterone somatostatin

Ultimate targets Many Muscles, Reproductive organs Liver, Mammary Smooth Arterioles Liver, Liver,
tissues liver bone glands muscle, muscles muscles,
mammary heart
glands
 POSTERIOR PITUITARY GLAND HORMONES
Oxytocin and Vasopressin are manufactured in the hypothalamus
(magnocellular neurons), but released in the posterior pituitary.
 r vo sa
a r s N e
P
Hypothalamic centers
Supraoptic nucleus
Paraventricular
nucleus
Axonal Transport
Pituicytes function
Neurohormones
Pituitary-Hypothalamic
Relationships:
Anterior Lobe
There is a vascular connection, the
hypophyseal portal system, consisting
of:
The primary capillary plexus
The hypophyseal portal veins
The secondary capillary plexus

InterActive Physiology®: Endocrine System: The Hypothalamic-Pituitary

Axis
ANTERIOR PITUITARY GLAND

Releasing vs. inhibiting factors

Hypophyseal portal system hypothalamic
neurons
releasing factor

arterial supply

primary plexus of
capillaries primary plexus
hypophyseal
veins

hypophyseal veins
secondary plexus

second plexus of
capillaries hormone
anterior
hypophyseal
vein

anterior hypophyseal veins

RELEASING HORMONES –
stimulate release of anterior
pituitary hormones.

INHIBITING HORMONES –
inhibit release of anterior
pituitaryNote Pituitary
hormones.
Portal System!!
 Pituitary & all Hormones are Under
the Control of the Hypothalamus
Hypothalamus

RF Hormon
e
Anterior Pituitary Posterior Pituitary

SH Hormon
e

Target Organs Target Organs

RF = Releasing Factor SH = Stimulating

Hormone
 Two Important Points:

Hormones released from the posterior

pituitary are synthesized in the
hypothalamus.

Hormones released from the anterior

pituitary are dormant unless directed to
be released by the hypothalamus via
Releasing Factors.
Hypothalamic Hormones:

Gondotropin RF Corticotropin RF Thyrotropin RF Growth Hor Prolactin RF

RF
(CRF)

Pituitary Hormones:

Adrenocorticoptropin Thyrotropin Growth Prolactin

Follicle SH &
SH Hormone
Lutenizing Hor. Hormone (ACTH)

Target Gland or Structure:

Cells of body Bones,

Ovaries & Testes Adrenal Gland Thyroid Gland breasts &
(androgens, (cortisol) (thyroxine) cells of body
estrogen)
 Control of
Adenohypophysial Hormones
neural inputs Hypothalamus
Indirect Short Releasing
Loop Loop Factor
Adenohypophysis
Trophic
Direct hormone
Loop Endocrine Gland
Endocrine
hormone
Target tissues

Some loops are negative feedback loops.

Increases in the amount of the substances monitored
reduces further secretion of those substances.
Summary of the Endocrine System

Figure 7-2-1: ANATOMY SUMMARY: Hormones

Summary of the Endocrine
System

Figure 7-2-2: ANATOMY SUMMARY: Hormones

Summary of the Endocrine
System

Figure 7-2-3: ANATOMY SUMMARY: Hormones

Figure 18.1
A Structural Classification of Hormones

Figure 18.2
G Proteins and Hormone Activity
Hormone Effects on Gene Activity
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Endocrine Gland Stimuli
PANCREA
S
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Pancreas
 PANKREAS

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Endocrine Pancreas

5151
TYPES OF TISSUES

1.Acini – secretes digestive juices

2.Islets of Langerhans- has 3 types of cells namely

● a. Alpha cells – 25% - secrete Glucagon

b.Beta cells – 60% - secrete Insulin and Amylin

c. Delta cells – 10% - secrete Somatostatin
d. PP cells – secrete pancreatic polypeptide
Insulin
Preproinsulin proinsulin insulin + peptide

c peptide: - MW 3000
- 31 aa
- no biologic activity
- released by  cell
- not removed by liver
- degraded & excreted by kidney
- T - 12 3 - 4 x insulin

Insulin: 51aa
A chain (21 aa)
 LEU SER GLY A LA
PR O GLN GLY
LEU PR O
GLY
ALA G LY

GLU
L EU GLY
10
C o n n e c tin g p e p tid e L EU

Signal peptide 31 IL E SER

GLY G LU
VA L

IL E LEU GLN

IL E GLN GLY
IL E
C -c h a in VA L

IL E GLN

IL E L EU SER GLY A LA
PR O G LN GLY LEU
L EU PRO
GLY
IL E ALA GLY
C -c h a in
GLU
L EU G LY
10 A SP
IL E
GLY C o n n e c tin g p e p tid e LEU
GLU

IL E
31 SER VA L G LU
LEU GLN

IL E GLN GLY
C -c h a in
ALA
D ip e p tid e VA L
IL E
lin k a g e L YS
GLU

ARG
GLN
1
A LA
LEU

GLU
1 GLY
C -c h a in A SP

G LY IL E GLU

IL E VA L
A -c h a in ALA

IL E GLU G LU

GLN S -C O O H 1
IL E
C YS ARG
IL E
C YS S A SH

PHE TH R C YS
21 ARG

1 VA L S
SER
IL E
A -c h a in T YR TH R
CYS ASN
ASN B -c h a in 10
SER
L EU TYR G LN LEU
GLU
B -c h a in
LYS

PRO
GLN
S S THR
H IS

LEU
In s u lin T YR

C YS PH E
PHE
S
G LY
PV HA EL
SER
H IS B -c h a in GLY
LEU ARG
VA L GLU
GLU GLY
10
A LA VAL C YS
L EU TYR L EU

20
 INSULIN – Hormone Associated with
Energy Abundance

1. Effect on Carbohydrate Metabolism

A. Promotes Muscle Glucose Uptake and Metabolism

-Storage of Glycogen in Muscle

B. Promotes Liver Uptake, Storage and Use of Glucose

Mechanisms:
● a. inactivates liver phosphorylase
b. causes enhanced uptake of glucose from the
blood by the liver cells (by increasing the
activity of the enzyme glucokinase
● C. increases activity of enzyme glycogen synthase , that
promote glycogen synthesis

- Glucose is released from the liver between meals

Lack of insulin activates Phosphorylase , which
causes splitting of glycogen into glucose phosphate

● - Insulin promotes Conversion of Excess Glucose

into
fatty Acids and Inhibits Gluconeogenesis in the
liver
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 Insulin bound toreceptor
sites

 
 

ATP P P P
Tyr Tyrosine Tyr P P
kinase P
P domains P
Tyr
PTyr Tyr
Tyr
TyrTyr
Tyr P P Tyr Tyr
P Tyr
P Carbonil-terminal Tyr
P IP3-kinase Translocation
Tyr domains p60 of GLUT-4
P
Tyr
P
Tyr ADP Tyr p110 p85
P Tyr
Tyr GLUT-4

Target
protein Tyr
IRS-1 Lipid metabolism
Amino acid
uptake Ion
P90-kinase
transport P70-kinase

DNA synthesis
Kinase activation Protein
Glicogen synthesis
synthesis Transcription factor phosphorilation
C. Lack of Effect of Insulin on Glucose Uptake and Usage
by the Brain
2. Effect on Fat Metabolism
A.Insulin promotes Fat Synthesis and Storage
● - Storage of Fat and the Adipose Cells

● a. insulin inhibits the action of hormone-

sensitive lipase

b. insulin promotes glucose transport through

the cell membrane into the fat cells
 ● B. Insulin deficiency Causes Increase Metabolic Use
of Fat causing

a . Lipolysis of Storage Fat and Release of Free

Fatty Acids
b. Increase Plasma Cholesterol and Phospholipid
c. Excess Usage of Fats during Insulin Lack
Causes
Ketosis and Acidosis
3. Effect of Insulin on Protein Metabolism
A. INSULIN PROMOTES PROTEIN Synthesis and Storage

a. stimulates transport of amino acids into the cells

(valine, leucine, isoleucine, tyrosine, phenylalanine)
b. increases the translation of messenger RNA,
forming new proteins
c. increases the rate of transcription of DNA genetic
sequences in cell nuclei
d. inhibits catabolism of proteins
e. depresses the rate of gluconeogenesis
 INSULIN PROMOTES PROTEIN FORMATION AND
PREVENTS DEGRADATION OF PROTEINS

B. Insulin Lack Causes Protein Depletion and Increased

Plasma Amino Acids
● - protein wasting is one of the most serious of
all effects of severe diabetes mellitus

C. Insulin and Growth Hormone Interact

Synergistically to
Promote Growth
MECHANISMS OF INSULIN SECRETION
 Pankreas

High blood
glucose

80 300
Insulin G lu c o s e

60 P e r io d o f g lu c o s e in fu s io n
Glucose
In s u lin
40 150

Insulin (ng/mL) 20

Glucose (ng/mL)
0 0
Blood 10 20 30 40 50 60
vessel M in
CONTROL OF INSULIN SECRETION
1. Increased Blood Glucose Stimulates Insulin secretion
2. Other Factors That Stimulate Insulin Secretion:
● a. Amino Acid – most potent are arginine and lysine
● - potentiates strongly the glucose stimulus for insulin secretion

● b. Gastrointestinal Hormones – Gastrin, Secretin,

cholecystokinin, Gastric Inhibitory Peptide

c. Other Hormones- Glucagon, Growth Hormone,

Cortisol, Progesterone and Estrogen
d. Autonomic Nervous System
● -Stimulation of the parasympathetic nerves to the pancreas
can increase insulin secretion
 Role of Insulin in “Switching” Between Carbohydrate
and Lipid Metabolism

GLUCAGON– a hormone secreted by the alpha cells of

the islets of Langerhans when blood glucose
concentration falls. Its important function is to increase
blood glucose concentration thus is also called the
Hyperglycemic Hormone.
 ● Effects on Glucose
Metabolism

Major Effects
1. breakdown of liver glycogen
(glycogenolysis)

2. increased gluconeogenesis in the liver

 Decrease in blood glucose

Release of
glucagon

Glucagon binds to membrane

receptor

Activation of adenylate cyclase

Increase in cAMP, activation of cAMP-dependent kinase

Activation of glycogen Inhibition of glycogen

phosporylase synthase

Degradation glycogen to glucose, release

of glucose into blood
 ● Other Effects (when conc. rises above maximum
normally found in the blood

1. activates adipose cell lipase- increasing fatty acids

available to the energy system of the body

2. inhibits storage of triglycerides in the liver

3. enhances the strength of the heart

4. increases blood flow in some tissues, esp. kidneys

5. enhances bile secretion

6. inhibits gastric acid secretion

 ● Regulation of Glucagon Secretion

● Increased Blood Glucose Inhibits Glucagon Secretion

● - the most potent factor that controls glucagon

secretion
- the effect of blood glucose conc. on glucagon
secretion is in exactly the opposite direction from the
effect of glucose on insulin secretion

● b. Increased Blood Amino Acids Stimulate Glucagon

Secretion (especially alanine and arginine)
The Regulation of Blood Glucose
Concentrations
 SOMATOSTATIN INHIBITS GLUCAGON
AND INSULIN SECRETION

Factors Related to Ingestion of Food Stimulate

Somatostatin Secretion:

● 1. Increased blood glucose

2. Increased amino acids
3. increased concentrations of GI hormones
4. increased fatty acids
Inhibitory Effects of Somatostatin:

1. Acts on the islets of Langerhans to depress the

secretion of insulin and glucagon

2. Decreases the motility of the stomach, duodenum and

gallbladder

3. Decreases both secretion and absorption in GIT

“ The Principal Role of Somatostatin” is to
extend the period of time over which the
food nutrients are assimilated into the
blood
 ● SUMMAR Y OF BLOOD GLUCOSE REGULATION
● Mechanisms:

1. The liver functions as an important blood glucose buffer

system
2. Both insulin and glucagon function as important
feedback control systems for maintaining a normal glucose
concentration
3. Severe hypoglycemia stimulates the sympathetic nervous
system
4. Growth hormone and cortisol are secreted in response to
prolonged hypoglycemia, decreasing the rate of glucose
utilization by most cells
Importance of Blood Glucose Regulation:

1. Glucose is the only nutrient that normally can be used

by the brain, retina and germinal epithelium of the
gonads

2. Blood glucose should not too high (reasons)

a. glucose exert a large amount of osmotic pressure in
the ECF causing cellular dehydration
b. high levels of blood glucose concentration causes loss
of glucose in the urine
c. causing osmotic diuresis by the kidneys
d. long-term increase in blood glucose cause damage to
many tissues, esp. blood vessels. Vascular injury
leads to heart attack, stroke, end-stage renal failure
and blindness
DIABETES MELLITUS

It is a syndrome of impaired carbohydrate,

fat, and protein metabolism caused by either
insulin lack or decreased sensitivity of the
tissues to insulin
Types of Diabetes Mellitus:
1. Type 1 Diabetes- also called insulin-dependent diabetes
mellitus (IDDM), is caused by lack of insulin secretion.

2. Type II Diabetes – also called non-insulin dependent diabetes

mellitus (NIDDM) , is caused by decreased sensitivity of
target tissues to insulin. This reduced sensitivity to insulin
is often referred to as insulin resistance

3. Other specific types of diabetes

4. Gestational diabetes mellitus (GDM)

 Type I Diabetes- Lack of Insulin
Production by Beta cells of the Pancreas

CAUSES:

1. Viral Infection or Autoimmune Disease – may

be involved in the destruction of the beta cells

2. Heredity

Usual onset of Type I diabetes occurs at about 14

years of age thus is often called Juvenile diabetes
mellitus
Principal Sequelae:
1. Increased blood glucose

2. Increased utilization of fats for

energy and for formation of
cholesterol by the liver

3. Depletion of the body’s proteins

● Blood Glucose Concentration Rises to
Very High Levels in Diabetes Mellitus

● Increased Blood Glucose Causes Loss of Glucose

in the Urine (>180 mg/100 ml)

● Increased Blood Glucose Causes Dehydration

● Osmotic diuresis, polyuria, intracellular
and
● extracellular dehydration, increased
thirst(polydipsia)
● Chronic High Glucose Concentration
Causes Tissue Injury:

● Blood vessels function abnormally resulting to

inadequate blood supply to tissues leading to risk of
heart attack, stroke, end- stage kidney disease,
retinopathy and blindness, and ischemia and
gangrene of the legs
Damage to tissues causing peripheral neuropathy
(abnormal function of peripheral nerves, and
autonomic nervous system dysfunction

● Hypertension (secondary to renal

injury) and arteriosclerosis (secondary
to abnormal lipid metabolism)
● Diabetes Mellitus Causes Increase Utilization of
Fats and Metabolic Acidosis leading to coma and
death

● As a result the patient develops severe metabolic

acidosis leading to coma and death

● Arteriosclerosis – increased deposition of

cholesterol in the arterial walls
● Kussmaul breathing - rapid and deep breathing –
physiologic compensation in metabolic acidosis
● Diabetes Causes Depletion of Body’s
proteins

●
- rapid weight loss and asthenia (lack of
energy) despite of eating large amounts of
food (polyphagia)
Type II Diabetes – Resistance to Metabolic
Effects of Insulin
● more common than type I – to 90% of all cases of
diabetes
● Onset occurs after the age of 30, often between 50 to

60 years
- referred to as Adult Onset Diabetes
- related mainly to the increasing prevalence of
obesity, the most important risk factor for type II
diabetes in children as well as adults

Obesity, Insulin Resistance and “Metabolic

Syndrome” Usually Precede Development of Type II
Diabetes
Features of Metabolic
Syndrome
1. Obesity, especially accumulation
of abdominal fat
2. Insulin resistance
3. Fasting hyperglycemia
4. Lipid abnormality such as
increased triglycerides and
decreased blood high – density
lipoprotein – cholesterol
5. hypertension
Other Factors That cause Insulin
Resistance and Type II Diabetes

1. Polycystic Ovary Syndrome (PCOS)

2. Excess formation of glucocorticoids
(Cushing Syndrome) or growth
hormone (acromegaly)

Development of Type II Diabetes

During Prolonged Insulin Resistance
Physiologic Diagnosis of Diabetes
Mellitus
1. Urinary Glucose
2. Fasting Blood Glucose and Insulin Levels
- in the early fasting blood glucose level is
normally 80 to 90 mg/100 ml
-110 mg/100 ml to be the upper limit
● FBS above this value indicates diabetes mellitus

● - type I diabetes – plasma insulin levels are very

low or undetectable during fasting and after a
meal
● type II diabetes – plasma insulin concentration is

higher than normal

● 3. Glucose Tolerance Test

● 4. Acetone breath
CONTROL OF HORMONE SECRETIONS

Negative feedback

hyperglycemia =
insulin secretion
110 mg%

[glucose] steady state

90 mg%
hypoglycemia =
glucagon secretion

time
TREATMENT OF DIABETES:

● A.Type I diabetes –administer enough insulin

● B. Type II diabetes
● dieting and exercise

● drugs
Insulinoma – Hyperinsulinism

● - occurs from an adenoma of an islet of Langerhans

- insulin shock and hypoglycemia

- as blood glucose level falls into the range of 50 to

70 mg/dl the CNS becomes excitable leading to
hallucinations, extreme nervousness, trembles
all over, breaks out in a sweat
Symptomatic results of insulin deficit
(diabetes mellitus)
 TERIMAKASIH

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