hipofise and pancreas

8/7/2019 Hipofise and Pancreas

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Dr. Bernhard Arianto Purba, M.Kes., AIFO

ANATOMI DAN FISIOLOGIHIPOFISE DAN PANKREAS


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Textbooks

Guyton, A.C & Hall, J.E. 2006. Textbook of Medical Physiology. The11th edition. Philadelphia: Elsevier-Saunders: 918-930, 961-977.

Brooks, G.A. & Fahey, T.D. 1985. Exercise Physiology. HumanBioenergetics and Sts Aplications. New York : Mac Millan PublishingCompany: 122-143.

Foss, M.L. & Keteyian, S.J. 1998. Foxs Physiological Basis forExercise 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 : McGrawHill.

Braunwald, Pauci, et al.2008. Harrison's PRINCIPLES OFINTERNAL MEDICINE. Seventeenth Edition. New York : McGrawHill: Chapter 332, 333, 338.

Kronenberg, and Melmed. 2008. WILLIAMS TEXTBOOK OFENDOCRINOLOGY. The 11th edition . Philadelphia: Elsevier-Saunders: 155-235, 1329-1407.


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General Features of theEndocrine System

1. Endocrine glands are ductless

2. Endocrine glands have a rich supply of blood.

3. Hormones, produced by the endocrine glands aresecreted into the bloodstream.

4. Hormones travel in the blood to target cells closeby or far away from point of secretion.

5. Hormones receptors are specific binding sites onthe target cell.


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Important Definitions

What are hormones?

Hormones are organic chemical messengers producedand secreted by endocrine cells into the bloodstream.

Hormones regulate, integrate and control a wide rangeof physiologic functions.

Silverthorn, Human Physiology, 3rd

edition Figure 6-1&2


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What are endocrine glands?

Endocrine glands are ductless glands comprised of endocrinecells. This means that these glands do not have ducts that lead tothe outside of the body. For example, sweat glands are NOTendocrine glands (they are instead exocrine glands) becausesweat glands have ducts that lead to the outside surface of yourskin (thats how the sweat gets out). The fact that endocrineglands are ductless means that these glands secrete hormones

directly into the blood stream (instead of to the outside of yourbody).


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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, aseries of cellular events unfold that eventually impactgene expression and protein synthesis.

Silverthorn, Human Physiology, 3rd

edition Figure 6-1&2


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What are hormone receptors?

Hormone receptors are binding sites on the target cell (eitheron the surface or in the cytoplasm or nucleus of the target cell)that are activated only when specific hormones bind to them. Ifa hormone does not/cannot bind to its receptor, then nophysiologic effect results.

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


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Growth hormone regulates cell growth

by binding to growth hormone


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Steps in Signal Communication

1. Synthesis2. Release3. Transport to target cell4. Signal detection by specific receptor

5. Change in cellular metabolism6. Signal removal termination cellular response

f


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Hypofunction Hyperfunction

Gland

ProH

Hormon

Response

Effector

Receptor

Degraded Degraded

Destruction

Block

Tumor

Antibodies

Block

Block

Hyperplasia

Stimulation

Iatrogenic

Ectopic production

Antibodiesantagonist

Tissue damage Tissue damage

Stimulation

Defect

Target cell


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Clinical Application

1111

Growth Hormone Ups and Downs

Gigantism - hypersecretion of GH in childrenAcromegaly hypersecretion of GH in adultsDwarfism hyposecretion of GH in children

Figure shows oversecretion of GH in adulthood as changes occur in thesame person at ages (a) nine, (b) sixteen, (c) thirty-three, and (4) fifty-two


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Master control

Master integrator

HYPOTHALAMUS

PITUITARY GLAND

AKA = hypophysis

1 cm in diameter

0,5-1 gr in weight

InfundibulumHypophysis stalk

Sella turcica

hypothalamus

infundibulum

pituitary gland

sella turcica insphenoid bone


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Click to edit Master text stylesSecond level

Third level Fourth level

Fifth level


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Anterior pituitary

(adenohypophysis)

PITUITARY GLAND (HYPOPHYSIS)

derived from Rathkespouch

Invagination of pharyngeal

epitheliumconnected tohypothalamus by

hypophyseal portalsystem

Posterior pituitary(neurohypophysis)

A neural tissue outgrowth ofhypothalamusconnected to hypothalamus

by

nerve tract

contains pituicytes

neurohypophyseal budfrom hypothalamus

infundibulum

bud from roof of mouthcalled Rathkes pouch

loses connectionwith mouth cavity

neurohypophysis

adenohypophysis


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Hypophysis or Pituitary Gland

D = pars distalis, I= pars intermediN = pars nervosa, S = stem or stalT = pars tuberalis

Posterior lobe Anterior lobe


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Pars distalis or anterior lobe

Pars nervosaor posterior lobe

Intermedia between black lines

uitary gland or Hypophysis

Adenohypophysis

eurohypophysis


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Hormones of the PituitaryGland

1818


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Hypothalamic

Hormones

1919


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Tissues can be targeted by multiple hormones

Hormones can act synergistically, permissively, orantagonistically

Synergistic effects ofhormones on bloodglucose concentration


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Neuroendocrineorigins of

signals

First target

Seconds targets

Ultimate targets

Sensory input from environment

Central nervous system

Hypothalamus

Hypothalamic hormones(releasing factors)

Anterior pituitary

Corticotropin(ACTH)

Mr4,500

Adrenalcortex

Cortisol

corticosterone,aldosterone

Manytissues

ThyrotropinMr28,000

Thyroid

Thyroxine

(T4), triiodothyronine (T3)

Muscles,liver

Folicle-stimulating

hormoneMr24,000

Ovaries/testes

Progesterone,

extradiol

Reproductive organs

Luteinizinghormone

Mr20,500

Testosterone

Somatotropin(growth hormone)

Mr21,500

Liver,bone

ProlactinMr22,000

Mammaryglands

Posterior pituitary

OxytocinMr1,007

Smoothmuscle,

mammaryglands

Vasopressin(antidiuretic

hormone)Mr1,040

Arterioles

Bloodglucose

level

Islet cells ofpancreas

Insulin,

glucogen,somatostatin

Liver,muscles

Adrenalmedulla

Epinephrine

Liver,muscles,

heart


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POSTERIOR PITUITARY GLAND HORMONESOxytocin and Vasopressin are manufactured in the hypothalamus(magnocellular neurons), but released in the posterior pituitary.


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sa


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Hypothalamic centersSupraoptic nucleus

Paraventricularnucleus

Axonal Transport

Pituicytes function

ParsNerv

osa


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Neurohormones


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Pituitary-HypothalamicRelationships:

Anterior LobeThere is a vascular connection, thehypophyseal portal system, consistingof:

The primary capillary plexus

The hypophyseal portal veins

The secondary capillary plexus

InterActive Physiology: Endocrine System: The Hypothalamic-PituitaryAxis

ANTERIOR PITUITARY GLAND


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Releasing vs. inhibiting factors

Hypophyseal portal system

ANTERIOR PITUITARY GLAND

arterial supply

primary plexus ofcapillaries

hypophyseal veins

second plexus ofcapillaries

anterior hypophyseal veins

hypothalamicneurons

releasing factor

primary plexushypophysealveins

secondary plexus

hormone

anteriorhypophysealvein


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Note PituitaryPortal System!!

RELEASING HORMONES stimulate release of anteriorpituitary hormones.

INHIBITING HORMONES inhibit release of anteriorpituitary hormones.


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Hypothalamus

Anterior Pituitary Posterior Pituitary

Target Organs Target Organs

RF

SH

Hormone

Hormone

RF = Releasing Factor SH = Stimulating

Hormone

Pituitary & all Hormones are Underthe Control of the Hypothalamus


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Two Important Points:

Hormones released from the posteriorpituitary are synthesized in the

hypothalamus.

Hormones released from the anteriorpituitary are dormant unless directed to

be released by the hypothalamus via

Releasing Factors.


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Hypothalamic Hormones:

Gondotropin RF Corticotropin RF

(CRF)

Thyrotropin RF Growth HorRF

Prolactin RF

Pituitary Hormones:

Follicle SH &

Lutenizing Hor.

ThyrotropinSH

Adrenocorticoptropin

Hormone (ACTH)

ProlactinGrowth

Hormone

Target Gland or Structure:

Ovaries & Testes

(androgens,

estrogen)

Adrenal Gland

(cortisol)

Cells of bodyThyroid Gland

(thyroxine)

Bones,breasts &cells of body


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Hypothalamus

Adenohypophysis

Endocrine Gland

Target tissues

Control ofAdenohypophysial Hormones

IndirectLoop

ShortLoop

DirectLoop

ReleasingFactor

Trophichormone

Endocrine

hormone

Some loops are negative feedback loops.Increases in the amount of the substances monitored

reduces further secretion of those substances.

eural inputs


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Summary of the Endocrine System

Figure 7-2-1: ANATOMY SUMMARY: Hormones


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Summary of the Endocrine

System



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Summary of the Endocrine

System



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Figure 18.1

A Structural Classification of Hormones


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Figure 18.2

A Structural Classification of Hormones

G Proteins and Hormone Activity


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y

Hormone Effects on Gene Activity


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Hormone Effects on Gene Activity

Click to edit Master text styles


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ySecond level


Fifth level

Endocrine Gland Stimuli


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Endocrine Gland Stimuli


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PANCREAS


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Fifth level


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Pancreas

PANKREAS


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PANKREAS



Fifth level

En ocr ne Pancreas


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5151

En ocr ne Pancreas


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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% - secreteInsulin and Amylinc. Delta cells 10% - secreteSomatostatind. PP cells secretepancreatic polypeptide


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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)


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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 theblood by the liver cells (by increasing the

activity of the enzymeglucokinase


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C. increases activity of enzyme glycogen synthase , that

promote glycogen synthesis

- Glucose is released from the liver between mealsLack of insulin activatesPhosphorylase , whichcauses splitting of glycogen into glucose phosphate

- Insulin promotes Conversion of Excess Glucoseinto

fatty Acids andInhibits Gluconeogenesis in theliver

Click to edit Master text stylesS d l l


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Second levelThird level

Fourth level

Fifth level

nsu n oun toreceptorsites


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Target

protein

P

Tyr

Translocationof GLUT-4

ATP

ADP

P

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

PTyr

Tyrosinekinase

domains

Carbonil-terminaldomains

P

GLUT-4

P

Tyr

Glicogen

synthesis

Proteinsynthesis

DNA synthesisKinase activation

Transcription factor phosphorilation

Lipid metabolismAmino aciduptake Iontransport

p60

p110 p85

IP3-kinase

IRS-1

P70-kinaseP90-kinase

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr

P

Tyr


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C. Lack of Effect of Insulin on Glucose Uptake and Usage

by the Brain


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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 throughthe cell membrane into the fat cells


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B. Insulin deficiency Causes Increase Metabolic Useof Fat causing

a. Lipolysis of Storage Fat and Release of FreeFatty Acids

b. Increase Plasma Cholesterol and Phospholipid

c. Excess Usage of Fats during Insulin LackCauses

Ketosis andAcidosis


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3. Effect of Insulin on Protein MetabolismA. 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 proteinsc. increases the rate of transcription of DNA geneticsequences in cell nuclei

d. inhibits catabolism of proteinse. depresses the rate of gluconeogenesis


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B. Insulin Lack Causes Protein Depletion and IncreasedPlasma Amino Acids

- protein wasting is one of the most serious ofall effects of severe diabetes mellitusC. Insulin and Growth Hormone InteractSynergistically to

Promote Growth

INSULIN PROMOTES PROTEIN FORMATION ANDPREVENTS DEGRADATION OF PROTEINS


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Bloodvessel

Insulin

High bloodglucose

Glucose

Pankreas

1 0 6 05 04 03 02 0

2 0

4 0

6 0

8 0

P e r i o d o f g l u c o s e i n f u s i o n

G l u c o s e

I n s u l i n

0

1 5 0

3 0 0

0

Insulin(ng/mL)

Glucose(ng/mL)

M i n

CONTROL OF INSULIN SECRETION


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CONTROL OF INSULIN SECRETION

1. Increased Blood Glucose Stimulates Insulin secretion


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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 pancreascan increase insulin secretion


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R l f I li i S it hi B t C b h d t


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Role of Insulin in Switching Between Carbohydrateand Lipid Metabolism

GLUCAGON a hormone secreted by the alpha cells of

the isletsof Langerhans when blood glucoseconcentration falls. Its important function is to increaseblood glucose concentration thus is also called the

Hyperglycemic Hormone.


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Effects on Glucose

Metabolism

Major Effects

1. breakdown of liver glycogen

(glycogenolysis)

2. increased gluconeogenesis in the liver

Decrease in blood glucose


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Release of

glucagon

Decrease in blood glucose

Glucagon binds to membranereceptor

Activation of adenylate cyclase

Increase in cAMP, activation of cAMP-dependent kinase

Activation of glycogenphosporylase Inhibition of glycogensynthase

Degradation glycogen to glucose, releaseof glucose into blood


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Other Effects (when conc. rises above maximumnormally found in the blood

1. activates adipose cell lipase- increasing fatty acidsavailable 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


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Regulation of Glucagon Secretion


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Regulation of Glucagon Secretion

Increased Blood Glucose Inhibits Glucagon Secretion

- the most potent factor that controls glucagonsecretion

- the effect of blood glucose conc. on glucagonsecretion isin exactly the opposite direction from the

effect of glucose oninsulin secretion

b. Increased Blood Amino Acids Stimulate Glucagon

Secretion (especially alanine and arginine)

The Regulation of Blood GlucoseConcentrations


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Concentrations

SOMATOSTATIN INHIBITS GLUCAGON


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SOMATOSTATIN INHIBITS GLUCAGONAND INSULIN SECRETION

Factors Related to Ingestion of Food StimulateSomatostatin Secretion:

1. Increased blood glucose2. Increased amino acids3. increased concentrations of GI hormones4. increased fatty acids


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Inhibitory Effects of Somatostatin:

1. Acts on the islets of Langerhans to depress thesecretion of insulin and glucagon

2. Decreases the motility of the stomach, duodenum andgallbladder

3. Decreases both secretion and absorption in GIT


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The Principal Role of Somatostatinis to

extend the period of time over which thefood nutrients are assimilated into theblood


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SUMMAR Y OF BLOOD GLUCOSE REGULATION Mechanisms:

1. The liver functions as an important blood glucose buffersystem2. Both insulin and glucagon function as important

feedback control systems for maintaining a normal glucoseconcentration3. Severe hypoglycemia stimulates the sympathetic nervoussystem 4. Growth hormone and cortisol are secreted in response to

prolonged hypoglycemia, decreasing the rate of glucoseutilization by most cells

Importance of Blood Glucose Regulation:


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1. Glucose is the only nutrient that normally can be usedby the brain, retina andgerminal 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 lossof glucose in the urinec. causing osmotic diuresis by the kidneysd. long-term increase in blood glucose cause damage to

many tissues, esp. blood vessels. Vascular injury

leads to heart attack, stroke, end-stage renal failureand blindness


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DIABETES MELLITUS

It is a syndrome of impaired carbohydrate,fat, and protein metabolism caused by eitherinsulin lackor decreased sensitivity ofthetissues to insulin

T f Di b t M llit


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Types of Diabetes Mellitus:

1. Type 1 Diabetes- also called insulin-dependentdiabetesmellitus (IDDM), is caused by lack of insulin secretion.

2.Type II Diabetes also called non-insulin dependentdiabetesmellitus (NIDDM) , is caused by decreased sensitivity of

target tissues to insulin. This reduced sensitivity to insulinis often referred to as insulin resistance

3. Other specific types of diabetes

4. Gestational diabetes mellitus (GDM)


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Type I Diabetes- Lack of InsulinProduction by Beta cells of the Pancreas

CAUSES:

1. Viral Infection or Autoimmune Disease maybe involved in the destruction of the beta cells

2. Heredity

Usual onset of Type I diabetes occurs at about 14years of age thus is often called Juvenile diabetesmellitus

Principal Sequelae:


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Principal Sequelae:

1. Increased blood glucose

2. Increased utilization of fats for

energy and for formation ofcholesterol by the liver

3. Depletion of the bodys proteins


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Blood Glucose Concentration Rises toVery 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)


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Chronic High Glucose ConcentrationCauses Tissue Injury:

Blood vessels function abnormally resulting toinadequate blood supply to tissues leading to riskof

heart attack,stroke,end- stage kidney disease,retinopathy and blindness, and ischemia and

gangrene of the legs

D t ti i i h l h


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Damage to tissues causingperipheral neuropathy(abnormal function of peripheral nerves, and

autonomic nervoussystem dysfunction

Hypertension (secondary to renalinjury) and arteriosclerosis (secondaryto abnormal lipid metabolism)


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Diabetes Mellitus Causes Increase Utilization ofFats 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 ofcholesterol in the arterial walls

Kussmaul breathing - rapid and deep breathing

physiologic compensation in metabolic acidosis


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Diabetes Causes Depletion of Bodys

proteins

- rapid weight loss and asthenia (lack of

energy) despite of eating large amounts offood (polyphagia)


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Type II Diabetes Resistance to MetabolicEffects of Insulin

more common than type I to 90% of all cases ofdiabetes

Onset occurs after the age of 30, often between 50 to

60 years- referred to asAdult Onset Diabetes- related mainly to the increasing prevalence of

obesity, the most important risk factor for type IIdiabetes in children as well as adults

Obesity, Insulin Resistance and MetabolicSyndrome Usually Precede Development of Type II

Diabetes

Features of Metabolic


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Features of MetabolicSyndrome1. Obesity, especially accumulation

of abdominal fat

2. Insulin resistance

3. Fasting hyperglycemia4. Lipid abnormality such as

increased triglycerides and

decreased blood high densitylipoprotein cholesterol

5. hypertension

Other Factors That cause Insulin


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Resistance and Type II Diabetes

1. Polycystic Ovary Syndrome (PCOS)

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

Development of Type II DiabetesDuring Prolonged Insulin Resistance


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Physiologic Diagnosis of Diabetes


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Mellitus

1. Urinary Glucose

2. Fasting Blood Glucose and Insulin Levels

- in the early fasting blood glucose level isnormally 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 verylow or undetectable during fasting and after ameal

type II diabetes plasma insulin concentration is

higher than normal

3. Glucose Tolerance Test

4. Acetone breath


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CONTROL OF HORMONE SECRETIONS


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Negative feedback

time

[glucose]

110 mg%

90 mg%

steady state

hyperglycemia =insulin secretion

hypoglycemia =

glucagon secretion


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TREATMENT OF DIABETES:

A.Type I diabetes administer enough insulin

B. Type II diabetes dieting and exercise drugs


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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 to70 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)


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(diabetes mellitus)


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TERIMAKASIH



Fifth level

hipofise and pancreas

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