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Organism Physiology I System/Organ Physiology

2 NH4+ 2 NH3

Na+ NHE3

H+

H+ ATPase H+ -KG 3Na+

glutamate dehydrogenase

gln

Na+

2 NH4+ Gluglutaminase

2 NH3 Gln CA-2 CO2

Cell & Molecular Physiology

H+
Glut 2K+

H2O

Na+

nHCO3NBC1

Blood

 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

Circulatory Digestive Endocrine Immune Integumentary Musculoskeletal Nervous Reproductive Urinary

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

 Structure and function Integration across Cells Tissues Organs Flow charts Follow process In sequence

Figure 1-3: Maps for physiology

Cell Intracellular fluid Extracellular fluid Organism Protective cells Exchange cells External environment Homeostasis Defined Emergent properties

Figure 1-4: The internal and external environments

Function and process are two related concepts in Physiology

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 thinking teleological 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
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 The how of a system The Mechanistic approach to physiological examines process The mechanistic answers to the question why do RBC transport oxygen? Is Oxygen binds to hemoglobin molecular contained in RBC? The concrete answer how oxygen transport occurs? But, says nothing about the significance of oxygen transport to the intact cell.

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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Organ Systems of the Human Body

System Name
Circulatory Digestive

Organs or Tissues
Heart, blood vessels, blood Stomach, intestines, liver, pancreas Thyroid gland, adrenal gland Thymus, spleen, lymph nodes Skin Skeletal muscles, bones Brain, spinal cord Ovaries and uterus, testes Lungs, airways Kidneys, bladder

Representative Functions
Transport of materials between all cells of the body Conversion of food into particles that can be transported int o the body; elimination of some wastes Coordination of body function through synthesis and release of regulatory molecules Defense against foreign invaders Protection from external environment Support and movement Coordination of body function through electrical signal and release of regulatory molecules Perpetuation of the species Exchange of oxygen and carbon dioxide between the internal and external environment Maintenance of water and solutes in the internal environment; waste removal

Endocrine Immune Integumentary Musculoskeletal Nervous Reproductive Respiratory Urinary

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Think about physiological functions we often consider their adaptive-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 physiology How? via cells/body systems Figure x
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Maintain

Body (organ) systems

Homeostasis

Make up

Is essential for survival of

Cells

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Mid 1800s Claude Bernard French Physician, Chairman of Physiology, University of Paris The concept of relatively stable environment Stability of various Physiological parameters: Body temperature, Heart Rate, Blood Pressure The constancy of the internal environment La fixit du milieu interieur

1929 Walter B. CannonAmerican Physiologist Homeostasis The regulation of this internal environment Homeo = like or similar > (better than) Homo Homo = same Internal environment is maintained within a range of values rather than at exact fixed value
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Stasis = condition Stasis static & unchanging

Precepts = aturan-ajaran-perintah A similar condition = a relatively constant internal environment

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3. The internal environment is dynamic and equilibrium (steady) state dynamic? equilibrium (steady) state?

What parameters are homeostatically regulated? 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 by OPPOSING 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 control variable (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 effector C. Effector action component that . . . Figure 1.9 (a-b)
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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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Fig. 1.10 Negative feedback in human thermoregulation.

Figure 1.11

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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

Next slide

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3. Details of birth of a baby Uterine contractions push the baby against the cervix the stretching of the cervix triggers nerve impulses brings about oxytocin secretion The hormone oxytocin causes even stronger powerful contractions of the uterus
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Q. Map and ID the sensor, integrator, and effector 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 normal function. Homeostasis: the regulation of the internal environment are central precepts of physiology.
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 External or internal change Loss of homeostasis Physiological attempt to correct Sensors, integrating center Response of cells & organs

 Successful compensation Homeostasis reestablished Failure to compensate Pathophysiology Illness Death

Figure 1-5: Homeostasis

Environmental factors that affect cells: Osmolarity Materials for cell needs: Temperature Nutrients pH Water Sodium Calcium Inorganic ions Oxygen
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 Having general & Continuous effects Hormones Our cells use to communicate with one another Chemicals If the body fails to maintain Homeostasis of these parameters Disrupted normal function and diseased state or pathological state/condition. Pathos-suffering

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1Internal failure of normal physiological process

Internal causes of disease: Abnormal growth of cells tumor, cancer The production of antibodies by the body against its own tissues (autoimmune diseases e.g. SLE (Systemic Lupus Erythematosus), Thyroiditis) The premature death of cells, failure of cell processes Inherited disorders
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2External causes of diseases:

Toxic chemicals Physical Trauma Foreign invaders e.g. Virus, Bacteria

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Fig. 1-4 Homeostasis

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2 If the compensation is successful homeostasis is

restored If the compensation fails illness or disease The study of body function in a disease state is known as pathophysiology Pathological condition: Diabetes Milletus A metabolic disorder: abnormally high glucose concentration Diabetes Milletus: whole family of diseases with various causes and manifestation

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Input signal controller output signal

Is programmed to respond to certain input signals

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Feedforward Controller

Figure 1-1
A 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 40 variable to the set point.

 Homeostasis Structure/function relationships Integration of systems Communication Membranes & exchange Energy Mass balance Mass flow & resistance

Figure 1-7: Mass balance in the body 41

Homeostatic mechanism regulates body temperature

Control center
The brain detects the deviation from the set point and signals effector organs.

Receptors
Thermoreceptors send signals to the control center.

Effectors Skin blood vessels dilate and sweat glands secrete.

Stimulus
Body temperature rises above normal. too high

Response
Body heat is lost to surroundings, temperature drops toward normal.

Normal body Temperature 37oC (98.6oF)

too low

Stimulus
Body temperature drops below normal.

Response
Body heat is conserved, temperature rises toward normal.

Receptors
Thermoreceptors send signals to the control center.

Effectors
Skin blood vessels constrict and sweat glands remain inactive.

Effectors
generates body heat.

Control center
The brain detects the deviation from the set point and signals effector organs.

If body temperature
continues to drop, control center signals muscles to contract involuntarily.

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

Homeostatic mechanism regulates body temperature Control center

The brain detects the deviation from the set point and signals effector organs.

Receptors
Thermoreceptors send signals to the control center.

Effectors
Skin blood vessels dilate and sweat glands secrete.

Stimulus
Body temperature rises above normal.

Response
Body heat is lost to surroundings, temperature drops toward normal.

too high

Normal body Temperature 37oC (98.6oF)

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

Homeostatic mechanism regulates body temperature

Normal body Temperature 37oC (98.6oF)

too low

Stimulus
Body temperature drops below normal.

Response
Body heat is conserved, temperature rises toward normal.

Receptors

Effectors

Effectors

Thermoreceptors send Skin blood vessels constrict and Muscle activity signals to the control center. sweat glands remain inactive. generates body heat.

Control center
The brain detects the deviation from the set point and signals effector organs. If body temperature continues to drop, control center signals muscles to contract involuntarily.

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

 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 <110mg/dl

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 Doctor explain to Mr. Teguh, Diabetes Mellitus Diabetes Mellitus is metabolic disorder caused by defection in the homeostatic pathway that regulate glucose metabolism Several type of DM
Diabetes Mellitus type1 Deficient production of insulin (protein hormone in the pancreas) Diabetes Mellitus type 2 Insulin present in normal or above normal Insulin sensitive cell of the body, dont respond normally to the hormone
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Amplifier Enzymes Amplifier Enzyme

Adenylyl cyclase

Celular Location
Membrane

Activated By
G protein-coupled receptor

Converts
ATP

To
cAMP

Guanylyl cyclase

Membrane Cytosol

Receptorenzyme Nitic oxide (NO)

GTP

cGMP

Phospholipase C

Membrane

G proteinMembrane coupled receptor phospholipids

Ip3 and DAG*

Ip3 = inositol trisphosphate; DAG= diacylglycerol

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Second Messenger Pathways

Second Messenger Ions Ca2+ Binds to calmodulin Binds to other proteins Alters enzyme activity Exocytosi, muscle contraction, cytoskeleton Phosphorylates proteins Action Effects

Nucleotides
cAMP Activates protein kinases, especially protein kinase A Binds to ion channels Activates protein kinases, especially protein kinase G Binds to ion channels

Alters channels opening

Phosphorylates proteins Alters channels opening

cGMP

Lipid-derived

IP3
DAG

Releases Ca2+ from intracellular stores

Activates protein kinase C

See effects Ca2+ above

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 second messenger system; The insulin receptor pathway at black box
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1889: Oscar Minkowski University of Strasbourg: Diabetespancreas 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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