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HOMEOSTASIS

Functional Organization of the Human Body


and Control of the “Internal Environment”
Physiology

The science that is concerned with the function


of the living organism and its parts, and of
the physical and chemical processes involved.

• Human Physiology
The Human Body - A Complex
Society of Differentiated Cells

• Cells: the basic structural and functional unit


(~ 100 trillion)
• Tissues: (e.g. muscles, epithelial, nervous )
• Organs: (e.g. kidney, heart, liver, pancreas)
• Organ systems: (e.g. cardiovascular, urinary)
Regulation and Integration
• Exists at all levels of organization

• Cells: e.g., genes, operons, repressor proteins,


transcription factors, membrane
transport
• Tissues: e.g., autacoids, paracrines
• Organ systems: e.g., nervous and endocrine
systems
Homeostasis

The maintenance of a stable


“ milieu interieur”
Claude Bernard (1813 - 1878)
General Organization
of the Circulatory
System

Figure 1-1;
Guyton & Hall
Exchange Between the Capillaries
and Interstitial Fluid

Figure 1-2; Guyton & Hall


Feedback Control

• Negative feedback: promotes stability


• Feed-forward: anticipates change
• Positive feedback: promotes a change
in one direction, instability, disease
WHAT HAPPENS IF THERE IS A CHANGE IN OUR
ENVIRONMENT?

 Depending upon the


degree of change:
 Discomfort
 Disease/sickness
 Damage/injury
 Death

 So any significant change


in the environment is
harmful for an organism.
LIFE ORIGINATED AS UNICELLULAR ORGANISMS
IN PRIMITIVE SEA
 The primitive sea was the
environment for the primitive
unicellular organisms.

 They obtained nutrition from it


and discharged wastes in it.

 The vastness of the sea kept its


composition almost constant.
UNICELLULAR ORGANISMS EVOLVED INTO
MUTLICELLULAR ORGANISMS

 Some cells in multicellular


organisms were away from
the primitive sea.

 As cells could not reach the


sea, the sea was brought
within in the form of
extracellular fluid.
60% OF HUMAN BODY IS WATER!
 40% is intracellular fluid (ICF)
i.e. fluid inside the cells.

 20% is extracellular fluid


(ECF) i.e. fluid outside the
cells. Further divided into:
 Interstitial Fluid (ISF)- 15%
 Plasma- 5%
ECF: THE INTERNAL ENVIRONMENT OF
THE BODY
 All the cells in the body live in
the same environment, the ECF.

 So, the ECF is also k/a ‘internal


environment’ of the body or
‘milieu intérieur’

 They get nutrition from it &


discharge their waste products
in it.
Walter B. Canon NAMED THE FIXITY DESCRIBED BY
Bernard AS ‘Homeostasis’
 American physiologist.

 Coined the term ‘homeostasis’.

 Described homeostasis as- ‘an


evolutionary development of a
metabolic wisdom that provides
for internal constancy’.

1871-1945
HOMEOSTASIS
 ‘maintenance of nearly
constant conditions in the
internal environment’.

 ‘the various physiologic


arrangements which serve
to restore the normal state,
once it has been disturbed’
are known as Homeostatic
Mechanisms.
WHAT NEEDS TO BE MAINTAINED CONSTANT IN
INTERNAL ENVIRONMENT?
1. Concentration of oxygen
and carbon dioxide.
2. pH of the internal
environment.
3. Concentration of
nutrients and waste
products.
4. Concentration of salt
and other electrolytes.
5. Volume and pressure of
extracellular fluid.
HOMEOSTASIS: AS DESCRIBED BY CANON

 perturbation in the organism’s steady state may arise from


changes within the organism as well as changes from without.

 homeostasis is not the responsibility of a single system but that all


the organ systems of the body operate cooperatively to effect
internal constancy.

 each cell benefits from homeostasis, and in turn, each cell


contributes its share toward the maintenance of homeostasis.

 the more “advanced” the evolutionary stage of a particular group


or organisms, the more subtle and complex the homeostatic
apparatus.
ALL ORGANS AND ORGAN SYSTEMS OF THE BODY HELP
IN MAINTENANCE OF HOMEOSTASIS

 Cardiovascular system.
 Respiratory system.
 Nervous system.
 Endocrine system.
 Gastrointestinal system.
 Excretory system.
 Skeletal system.
 Integumentry system.
 Reproductive system.
CARDIOVASCULAR SYSTEM
 Transports oxygen,
carbon dioxide,
nutrients and
hormones to and from
the body cells.
 Helps regulate pH and
temperature.
 Provides protection
against diseases.
RESPIRATORY SYSTEM

 Exchange the gases


between atmospheric
air and blood.

 Help adjust the pH of


the body fluids.
NERVOUS SYSTEM

 Generates nerve
impulses (Action
Potential) that provide
communication and
regulation of most
body tissues.
ENDOCRINE SYSTEM
 Regulates the activity
and growth of target
cells in the body.

 Regulate metabolism
GASTROINTESTINAL SYSTEM
 Breaks down food into
absorbable form.

 Absorbs various
nutrients.

 Eliminates waste from


the body.
EXCRETORY SYSTEM
 Helps eliminate the
waste products from
the body.
 Maintains the blood
pH, volume, pressure,
osmolarity, electrolyte
composition etc.
 Produces hormones.
SKELETAL SYSTEM
 Bones provide support,
protection, the
production of blood
cells.

 Muscles produce body


movements and produce
heat to maintain the
body temperature.
INTEGUMENTARY SYSTEM
 Contributes to
homeostasis by
protecting the body
and helping regulate
the body temperature.
It also allows you to
sense pleasurable,
painful and other
stimuli in your
external environment.
REPRODUCTIVE SYSTEM
 Sometimes reproduction
is not considered a
homeostatic function.
 Helps maintain
homeostasis by
generating new beings to
take the place of those
that are dying and thus
help in maintaining the
continuity of life.
HOW HOMEOSTATIC CONTROL MECHANISMS
WORK?
 Homeostatic control
mechanisms work
through ‘Feedback
Mechanisms’.

 Status of a body
condition is
continually monitored,
evaluated, changed, re-
monitored &
reevaluated.
FEEDBACK MECHANISM
 A feedback mechanism is a cycle in which the
output of a system “feeds back” to either modify or
reinforce the action taken by the system.

 A feedback mechanism may operate at:


 Tissue level
 Organ level
 Organ system level
 Body level, integrating with other organ systems.

 Feedback mechanism can be:


 Negative feedback (more common)
 Positive feedback
A FEEDBACK SYSTEM CONSISTS OF THREE
COMPONENTS
1. SENSOR (RECEPTOR):
detects specific changes
(stimuli) in the
environment.

2. INTEGRATOR: act to direct


impulses to the place where
a response can be made.

3. EFFECTOR: performs the


appropriate response.
A FEEDBACK LOOP
NEGETIVE FEEDBACK
 Mechanisms that maintain the factor at some
mean value.
 Reverse a change
 Restore abnormal values to normal
NEGATIVE FEEDBACK LOOP
EXAMPLE: NEGATIVE FEEDBACK
BLOOD PRESSURE REGULATION
POSITIVE FEEDBACK
 Strengthens or reinforces a change.
 Makes abnormal values more abnormal.
 Produces ‘Vicious Cycle’.
 But in body a mild degree of positive feedback can be
overcome by the negative feedback control
mechanisms of the body, and the vicious cycle fails to
develop.
POSITIVE FEEDBACK LOOP
EXAMPLE: POSITIVE FEEDBACK
MEMBRANE DEPOLARISATION
POSITIVE FEEDBACKS IN BODY
 Action potential
 Clotting of blood
 Parturition
 Release of calcium
from SR
 Sexual arousal
 LH surge
NEGATIVE Vs POSITIVE
FEEDBACK
EFFECTIVENESS OF A FEEDBACK CONTROL
THE PRINCIPLE OF GAIN
GAIN = Correction/Error
Higher the gain, more efficient is the system
Normal BP = 100 mm Hg

Some disturbance causes an ↑ BP = 175 mm Hg

Baroreceptor mechanism brings BP down to 125 mm Hg

So correction done by baroreceptor mechanism = - 50 mm Hg

But still error = 25 mm Hg

So, Gain = - 50/25 = - 2


FINAL OUTCOME OF
HOMEOSTATIC PROCESSES
Negative Feedback Control of Arterial
Pressure Promotes Stability

Art. Pressure Sympathetic


Activity

Heart Rate
Vasoconstriction
Baroreceptor Reflex :
Negative Feedback System - Promotes Stability

Set-point
Error signal Effectors
+
Vasomotor Sympathetic Blood vessels,
Centers System Heart

Controlled
Sensor Variable
Blood
Baroreceptors
Pressure
Cardiopulmonary Reflexes:
Feed-Forward Control of Blood Pressure –
Anticipates a Change

Cardiopulmonary Cardiopulmonary
Receptors Pressures
Set-point
+ Error signal Effectors

Vasomotor Sympathetic Blood vessels,


Centers System Heart
Controlled
Sensor Variable

Blood
Baroreceptors
Pressure
Feedback Gain

A measure of the effectiveness of a feedback system

Correction
Gain =
Error
What is the feedback gain in this example ?

Hemorrhage 1.5 liters

100
Arterial Pressure “ error ” = + 25
75
feedback
= - 25
“correction”
50

Correction - 25
Gain = = = - 1.0
Error 25
Feedback and Feed-Forward Control

• Negative feedback: promotes stability


• Feed-forward: anticipates change
• Positive feedback: promotes a change
in one direction, instability, disease
Positive Feedback of Hemorrhagic Shock

Figure 1-3;
Guyton & Hall
Hemorrhagic Shock:
Positive Feedback
Severe Hemorrhage

Venous Return
+
Cardiac Output
Blood Pressure
Coronary Blood Flow

Cardiac Contractility
Action Potential:
Positive Feedback

Cell Depolarization

+
Cell Na Permeability

Na Influx

Cell Membrane Potential


Homeostatic Control of
Metabolism
Food Intake
 How does your body know when to eat?
 How does your body know how much to eat?

 Two ‘competing’ behavioral states:


 Appetite = desire for food
 Satiety = sense of fullness
Hypothalamic Centers
 Feeding center – tonically active
 Satiety center – inhibits feeding center

Figure 11-3
Regulation: Classic Theories
 Glucostatic theory: glucose levels control the
feeding and satiety centers in hypothalamus
 Low [glucose] – satiety center suppressed
 High [glucose] – satiety center inhibits feeding center

 Lipostatic theory: body fat stores regulate the


feeding and satiety centers
 Low fat levels  increased eating
 Recent discovery of leptin and neuropeptide Y provides
support
Peptides Regulate Feeding
 Input to hypothalamus:
 Neural from cerebral cortex
 Neural from limbic system
 Peptide hormones from GI tract
 Adipocytokines from adipose tissue
Peptides Regulate Feeding

Note the diversity


of peptide origins!

cholecystokinin =
Peptides Regulate Feeding

inhibition

Figure 22-1
We Eat To Do Work
 Energy input = energy output
 Energy output = work + heat
 3 categories of work:
 Transport work – moving molecules from one side of
membrane to the other
 Mechanical work – movement
 Chemical work – synthesis and storage of molecules
 Short-term energy storage – ATP
 Long-term energy storage – glycogen, fat
Metabolism
= sum of all chemical reactions in the body

 Anabolic pathways – synthesize large


molecules from smaller
 Catabolic pathways – break large molecules
into smaller
Metabolism
 Divided into two states:
 Fed (or Absorptive) state
 After a meal
 Anabolic – energy is stored

 Fasted (or Post-absorptive) state


 Molecules from meal no longer in bloodstream
 Catabolic – storage molecules broken down
Fate of Ingested Molecules
 Immediate use in energy production: nutrient
pools
 Synthesis into needed molecules (growth,
maintenance)
 Storage for later use

 Fate depends on type of molecule:


carbohydrate, protein, or fat
DIET

Fats Carbohydrates Proteins

Free fatty acids + glycerol


Build
proteins
Excess
Protein
stored Glycogenesis Amino synthesis
Glucose Excess acids
Lipogenesis

Fat Lipogenesis
stores Excess glucose stored
Glycogen Body
stores protein
Lipolysis Urine
Glycogenolysis
Glucose pool
Gluconeogenesis
Free fatty
Range of normal
acid pool
plasma glucose Amino acid
Many pool

immediately Excess converted


used Many
in liver
Metabolism in immediately
Brain
most tissues used
Excess nutrients metabolism

Figure 22-2
What Controls This?
 Hormones control metabolism by altering
enzyme activity and molecule movement

 Push-pull control: different enzymes catalyze


forward and reverse reactions
Push-Pull Control

INSULIN
enzyme 1 enhanced,
enzyme 2 inhibited

enzyme 1 inhibited,
enzyme 2 enhanced
GLUCAGON

Figure 22-4
Metabolism is Controlled by Ratio of
Insulin and Glucagon

Anabolic

Catabolic

Figure 22-9
Fed State

Many
immediately
used
Fasted State
1 Liver glycogen
becomes glucose.
2 Adipose lipids
become free
fatty acids and Triglyceride stores
glycerol that
enter blood.

Liver Free fatty Free fatty


Glycerol
glycogen acids acids
stores
Glycogenolysis -oxidation
Gluconeogenesis

Energy Ketone
production bodies Energy production
Glucose

Glycogen Proteins

Gluconeogenesis
Pyruvate
or
Lactate
Amino
Ketone acids
Glucose
bodies

Energy production
3 Muscle glycogen can be used for energy.
4 Brain can use Muscles also use fatty acids and break
only glucose and down their proteins to amino acids that
ketones for energy. enter the blood.
Figure 22-7
Pancreas – Islets of Langerhans

Figure 22-8
Insulin
 Origin in β cells of
pancreas
 Peptide hormone
 Transported dissolved
in plasma
 Half-life ~5 min
 Target tissues: liver,
muscle, adipose tissue
Insulin
 Secretion promoted by:
 High plasma [glucose] (> 100 mg/dL)
 Increased plasma amino acids
 Feedforward effects of GI hormones
 Glucagon-like peptide-1 (GLP-1)
 Gastric inhibitory peptide (GIP)
 Anticipatory release of insulin
 Parasympathetic input to β cells
 Secretion inhibited by:
 Sympathetic input
 Reduced plasma [glucose]
Insulin Mechanism of Action
Extracellular
Insulin 1 Insulin binds to tyrosine
fluid
kinase receptor.

1
2 Receptor phosphorylates
insulin-receptor substrates (IRS).

3 Second messenger pathways


GLUT4 alter protein synthesis and
2 existing proteins.
IRS IRS P Transport
4
3 activity 4 Membrane transport
is modified.
Second
Nucleus messenger
pathways Enzymes or
5 Cell metabolism is
5 changed.
Transcription
factors Changes in
metabolism

Figure 22-11
Insulin Lowers Plasma Glucose
1. Increases glucose transport into most insulin-
sensitive cells
2. Enhances cellular utilization and storage of
glucose
3. Enhances utilization of amino acids
4. Promotes fat synthesis
Insulin Increases Glucose Transport
 Required for resting skeletal muscle and
adipose tissue
 Moves GLUT-4 transporters to cell membrane
 Exercising skeletal muscle does not require
insulin for glucose uptake

 In liver cells, indirect influence on glucose


transport
Insulin Increases Glucose Transport:
Skeletal Muscle & Adipose Tissue

GLUT-4 transporters moved to cell membrane


Figure 22-12
Insulin Increases Glucose Transport:
Indirect in Liver Cells

Insulin activates hexokinase, keeps IC [glucose] low Figure 22-13


Insulin Enhances Utilization and
Storage of Glucose
 Activates enzymes for:
 Glycolysis – glucose utilization
 Glycogenesis – glycogen synthesis
 Lipogenesis – fat synthesis
 Inhibits enzymes for:
 Glycogenolysis – glycogen breakdown
 Gluconeogenesis – glucose synthesis
Insulin Enhances Utilization of
Amino Acids
 Activates enzymes for protein synthesis in liver
and muscle
 Inhibits enzymes that promote protein
breakdown (no gluconeogenesis)
 Excess amino acids converted into fatty acids
Insulin Promotes Fat Synthesis
 Inhibits β-oxidation of fatty acids
 Promotes conversion of excess glucose into
triglycerides
 Excess triglycerides stored in adipose tissue
Energy Glucose
storage metabolism

Figure 22-14
Glucagon
• Origin in α cells of pancreas
• Peptide hormone
• Transported dissolved in plasma
• Half-life ~5 min
• Target tissues: mostly liver
• α cells require insulin to uptake glucose
Glucagon
• Secretion promoted by:
– Low plasma [glucose] (< 100 mg/dL)
– Increased plasma amino acids
– Sympathetic input

• Secretion inhibited by increased [glucose]

• Inhibition by insulin??
Glucagon Raises Plasma Glucose

 Main purpose is to respond to hypoglycemia

 Activates enzymes for:


 Glycogenolysis – glycogen breakdown
 Gluconeogenesis – glucose synthesis
Response to Hypoglycemia in Fasted State

Figure 22-15
Diabetes Mellitus
 Family of diseases
 Chronic elevated plasma glucose levels
= hyperglycemia
 Two types:
 Type 1 – insulin deficiency
 Type 2 – ‘insulin-resistant’ diabetes; cells do not
respond to insulin
Type 1 Diabetes
 ~10% of cases
 Absorb nutrients normally, but no insulin
released – what happens?
 Cells shift to fasted state, leading to glucose
production!
 Results in hyperglycemia and cascading effects
Figure 22-16
Type 2 Diabetes
 ~90% of cases
 Target cells do not respond normally to insulin
 Delayed response to ingested glucose
 Leads to hyperglycemia
 Often have elevated glucagon – why?
 No uptake of glucose by α cells

 Release glucagon
 Exercise and modified diet help treat – why?