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OrganismPhysiology Cell & MolecularPhysiology

nHCO3-

NBC1

Na+

H+

3

Na+

2

K+

Blood

CO2

H2O

Na+

ATPase

H+

NHE3

H+

Na+

gln

Glut

CA-2

Gln

G

lu-

-KG

glutaminase

glutamate

dehydrogenase

2NH3

2NH3

2NH4+

H+

2NH

4+

System/OrganPhysiology

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Physiology defined:

Function explains why it needs to be done Mechanism explains how it does that job

Organization of life

The cell is the unit of life Cells, tissues, organs, organ systems & organisms

Figure 1-1: Levels of organization and the related fields of study

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Circulatory Digestive

Endocrine

Immune Integumentary

Musculoskeletal

Nervous

Reproductive

UrinaryFigure 1-2: The integration between systems of the body

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Structure and function

Integration across

Cells

Tissues

Organs

Flow charts

Follow process

In sequence

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Figure 1-3: Maps for physiology

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Cell Intracellular fluid

Extracellular fluid

Organism

Protective cells

Exchange cells

External environment

Homeostasis Defined

Emergent properties Figure 1-4: The internal and external environments

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The Function of a Physiological system or event is the

why of the system or event why does the system exist,

why does the event happened? This way of thinkingteleological approach e.g: why RBC

transport oxygen system is because cells need oxygen

and RBC is bring it to them. The answer explain the reason RBC transport O2

says nothing about how the cell transport

system

Function and process are two related concepts in

Physiology

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The how of a system

The Mechanistic approach to physiological examinesprocess

The mechanistic answers to the question why do RBC

transport oxygen? Is Oxygen binds to hemoglobinmolecular contained in RBC?

The concrete answer how oxygen transport occurs?

But, says nothing about the significance of oxygentransport to the intact cell.

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To answer the question with teleological explanation when

the appropriate response would be mechanistic explanation.

Q : why a physiological event occurs?

When she or he wants to know how

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System Name Organs or Tissues Representative Functions

Circulatory Heart, blood vessels, blood Transport of materials between all cells of the

body

Digestive Stomach, intestines, liver,

pancreas

Conversion of food into particles that can be

transported int o the body; elimination of some

wastes

Endocrine Thyroid gland, adrenal gland Coordination of body function through synthesis

and release of regulatory molecules

Immune Thymus, spleen, lymphnodes

Defense against foreign invaders

Integumentary Skin Protection from external environment

Musculoskeletal Skeletal muscles, bones Support and movement

Nervous Brain, spinal cord Coordination of body function through electrical

signal and release of regulatory moleculesReproductive Ovaries and uterus, testes Perpetuation of the species

Respiratory Lungs, airways Exchange of oxygen and carbon dioxide between

the internal and external environment

Urinary Kidneys, bladder Maintenance of water and solutes in the internal

environment; waste removal 11

Organ Systems of the Human Body

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Think about physiological functions we often considertheiradaptive-significance

The organism that survive in those challenging habitats cope

with external variability by keeping their internal

environment relatively stable, an ability known as

homeostasis.

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1. Definition Maintenance of stable conditions in

the internal environment

2. Importance of homeostasis:

A. Homeostasis is essential for survival of cells

Why? Insight 1.3 (Men in the Oven for 45

minutes; p. 18)

B. Cells make up the body systems

C. Homeostasis is the central theme of physiologyHow? via cells/body systems

Figure x

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Maintain

Body (organ) systems Homeostasis

Cells

Make up

Is essential

for

survival

of

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Mid 1800sClaude Bernard FrenchPhysician, Chairman of

Physiology, University ofParis

The concept of relativelystable environment

Stability of variousPhysiological parameters:

Body temperature, HeartRate, Blood Pressure

The constancy of theinternal environment Lafixit du milieu interieur

1929 Walter B. Cannon-American Physiologist

Homeostasis Theregulation of this internal

environmentHomeo = like or similar >

(better than) Homo

Homo = same

Internal environment ismaintained within a range ofvalues rather than at exact

fixed value

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Stasis = condition

Stasis static & unchanging

Precepts = aturan-ajaran-perintahA similar condition = a relatively constant internal

environment

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3. The internal environment is dynamicandequilibrium (steady) state

dynamic?

equilibrium (steady) state?

What parameters are homeostaticallyregulated?

Chemical factors

Physical factors

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1. Definition change in a factor (controlled

variable) triggers a physiological response

that seeks to restore the factor byOPPOSING the initial change

2. Examplecontrol of room/body

temperature

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3. Three components of a control system

A. Sensor (receptor) monitors the controlvariable (for example, room temp.); what is the

sensor?B. Integrating (control) center it compares the

sensors input with the set point and sends

instructions to effectorC. Effector action component that . . .

Figure 1.9 (a-b)19

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Sensor?

Integrating

center?

Effector?

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Fig. 1.9(b) Fluctuation of room temperature around

the thermostatic set point

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Figure 1.11

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Fig. 1.10 Negative feedback

in human thermoregulation.

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1. Definition change in a factor triggers a

physiological response that AMPLIFIES an

initial change

2. Example in the birth of a baby; how?

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Figure 1.12--Positive

feedback in childbirth

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Nextslide

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3. Details of birth of a baby

Uterine contractions push the babyagainst the cervix

the stretching of the cervix triggers nerve

impulses

brings about oxytocin secretion

The hormone oxytocin causes even

stronger powerful contractions of theuterus

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Q. Map and ID the sensor, integrator, andeffector of the above example (child birth).

Then explain the homeostatic control

system. Why this is a positive negative

feedback?

Assuming: Controlled variable--Stretching of

the cervix

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Homeostasis : a state of standing static or unchanging Homeodynamics : to reflect the small changes

constantly taking place in our internal environment

Dynamikos = force of power Homeostasis or Homeodynamics the importance

concept is the body monitors its internal state & take

action to correct disruptions that threaten its normalfunction.

Homeostasis: the regulation of the internal environment

are central precepts of physiology. 30

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External or internal change

Loss of homeostasis

Physiological attempt to correct

Sensors, integrating center Response of cells & organs

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Successful compensation Homeostasis

reestablished

Failure to compensate Pathophysiology

Illness

Death

Figure 1-5: Homeostasis

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Environmental factors that affect cells:

Osmolarity

Temperature

pH

Materials for cell needs:

Nutrients Water

Sodium

Calcium Inorganic ions

Oxygen33

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Having general & Continuous effects

Hormones

Chemicals

If the body fails to maintain Homeostasis of these

parameters Disrupted normal function and diseased

state or pathological state/condition.

Pathos-suffering

Our cells use to communicate with

one another

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Internal failure of normal physiological processInternal causes of disease:

Abnormal growth of cells tumor, cancer

The production of antibodies by the body against itsown tissues (autoimmune diseases e.g. SLE

(Systemic Lupus Erythematosus), Thyroiditis)

The premature death of cells, failure of cellprocesses

Inherited disorders

1

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External causes of diseases: Toxic chemicals

Physical Trauma

Foreign invaders e.g. Virus, Bacteria

2

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37Fig. 1-4 Homeostasis

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2

If the compensation is successful

homeostasis isrestored

If the compensation fails illness or disease

The study of body function in a disease state isknown as pathophysiology

Pathological condition: Diabetes Milletus

A metabolic disorder: abnormally high glucoseconcentration

Diabetes Milletus: whole family of diseases with

various causes and manifestation 38

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Input signal controller output signal

Is programmed to

respond to certaininput signals

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40

Feedforward

Controller

Figure 1-1A standard homeostasis system consists of five elements set point, sensor, integration center,

effector, and regulated variable. Most homeostasis systems are designed to keep the regulated

variable to the set point.

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Homeostasis

Structure/function

relationships

Integration of systems

Communication

Membranes & exchange

Energy

Mass balance

Mass flow & resistanceFigure 1-7: Mass balance in the body

Homeostatic mechanism regulates body temperature

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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Control centerThe brain detects thedeviation from the setpoint and signals effectororgans.

ReceptorsThermoreceptorssendsignals to the control center.

EffectorsSkin blood vessels dilate

and sweat glands secrete.

StimulusBody temperature

rises above normal.

ResponseBody heat is lost to surroundings,

temperature drops toward normal.

too high

too low

Normal body

Temperature

37oC (98.6oF)

StimulusBody temperaturedrops below normal.

ResponseBody heat is conserved,temperature rises toward normal.

ReceptorsThermoreceptors sendsignals to the control center.

EffectorsSkin blood vessels constrict andsweat glands remain inactive.

Effectorsgenerates body heat.

Control centerThe brain detects thedeviation from the set pointand signals effector organs.

If body temperaturecontinues to drop, controlcenter signals muscles to

contract involuntarily.

Homeostatic mechanism regulates body temperature

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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Control centerThe brain detects thedeviation from the set

point and signals effectororgans.

ReceptorsThermoreceptors sendsignals to the control center.

EffectorsSkin blood vessels dilateand sweat glands secrete.

StimulusBody temperaturerises above normal.

ResponseBody heat is lost to surroundings,temperature drops toward normal.

too high

Normal bodyTemperature37oC (98.6oF)

Homeostatic mechanism regulates body temperature

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EffectorsSkin blood vessels constrict andsweat glands remain inactive.

ReceptorsThermoreceptors sendsignals to the control center.

too low

Normal bodyTemperature

37oC (98.6oF)

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

StimulusBody temperaturedrops below normal.

ResponseBody heat is conserved,temperature rises toward normal.

EffectorsMuscle activitygenerates body heat.

Control centerThe brain detects thedeviation from the set pointand signals effector organs.

If body temperaturecontinues to drop, controlcenter signals muscles tocontract involuntarily.

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Cell to cell communication 75 trillion cells

What is DM?

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Mr. Teguh

age 25 years, hungry

Fasting blood sugar 160mg/dl

Normal Fasting blood sugar

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Doctor explain to Mr. Teguh, Diabetes Mellitus

Diabetes Mellitus is metabolic disorder caused bydefection in the homeostatic pathway that regulate

glucose metabolism

Diabetes Mellitus type1

Deficient production ofinsulin (protein hormone

in the pancreas)

Diabetes Mellitus type 2

Insulin present in normal

or above normalInsulin sensitive cell of the

body, dont respondnormally to the hormone

Several type of DM

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Amplifier Enzyme Celular Location Activated By Converts To

Adenylyl cyclase Membrane G protein-coupled

receptor

ATP cAMP

Guanylyl cyclase Membrane Cytosol Receptor-

enzyme Niticoxide (NO)

GTP cGMP

Phospholipase C Membrane G protein-

coupled receptor

Membrane

phospholipids

Ip3 and

DAG*

Ip3 = inositol trisphosphate; DAG= diacylglycerol

Amplifier Enzymes

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Second Messenger Pathways

SecondMessenger

Action Effects

Ions

Ca2+ Binds to calmodulin

Binds to other proteins

Alters enzyme activity

Exocytosi, muscle contraction,

cytoskeletonNucleotides

cAMP Activates protein kinases, especially

protein kinase A

Binds to ion channels

Phosphorylates proteins

Alters channels opening

cGMP Activates protein kinases, especiallyprotein kinase G

Binds to ion channels

Phosphorylates proteins

Alters channels opening

Lipid-derived

IP3 Releases Ca2+ from intracellular stores See effects Ca2+ above

DAG Activates protein kinase C Phosphorylates proteins

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Insulins signal transduction pathway

Type 2 Diabetes Mellitus

Hormone insulin binds to its receptor

Research: investigate -the insulin receptor-its clinical pathway

Results :

Insulin does not use the well studied CAMP secondmessenger system;

The insulin receptor pathway at black box

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1889:

Oscar MinkowskiUniversity of Strasbourg: Diabetes-

pancreas

1921:

Frederick G. Banting-Charles H. Best: Insulin

1922:

First Clinical TRIAL

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1982:

Scientis discovered that insulin receptor tyrosine kinase

receptor enzyme

Tyrosine kinase was phosphorylating

8 substrate for the insulin receptor kinase

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