Chapter 1 - Homeostasis Human Physiology 1-19

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Chapter 1
-

Homeostasis

Human Physiology 1
-
19

Page
1

of

7

I.

Chapter
1

-

Introduction

A.

Scope of Human Physiology

1.

Physiology versus Development

2.

Physiology versus Pathophysiology

B.

Body Organization


Review

1.

Cellular Differentiation

2.

Hierarchy
→ atoms to biosphere

C.

Body Fluid Compartme
nts

1.

Intracellular versus Extracellular

2.

Intracellular events are controlled by regulating extracellular
events

II.

General Characteristics of Homeostatic Control Systems

A.

Compare marine environment with terrestrial and the origin of life

1.

Importance of maintainin
g constant internal environment

2.

Claude Bernard and W.B. Cannon

B.

Homeostasis

-

literally translated means "constant state"

1.

Also known as cybernetics
, negative feedback

mechanisms
and servomech
anisms

2.

The term
cybernetics

was taken from the Greek word
kubernetes

meaning steersman or pilot

3.

Homeostatic mechanisms maintain relatively stable
conditions in the extracellular environment

C.

Definitio
n of homeostatic

system

1.

A control system which consists of a collection of
interconnected cells which function to maintain a physical or
chemical property of the body relatively constant

2.

General properties of homeostasis

(temperature control or
thermoregu
lation as example)

3.

Below is a model of the general principles of homeostasis

Set point
Set point
(+)
(-)
Upward
Deviation
Downward
Deviation
Positive or
Runaway
Feedback
Negative
Feedback
Positive or
Runaway
Feedback
Negative
Feedback

a)

Error signal

= degree of t
olerance or temporary set
point

b)

Table
1
-
2
, page 1
1
, five generalizations

(1)

Balancing inputs and outputs

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(2)

Negative feedback


response is in
opposite direction to deviation

(3)

Do not maintain absolutely but rather within
a variable range depending on importance
of homeostatic mechanism

(4)

Some set points can be reset

(5)

Homeostatic mechanisms operate on a
hierarchy

of importance

a)

Set point

= operating point

b)

Any return to the set point is called
negative
feedback

c)

Any deviation that causes further deviation is termed
positive or runaway feedback

d)

Not all negative feedback

is good and not all positive
feedback is bad
-

depends on the parameter in
question
-

the terms positive and negative do NOT
connote benefit or harm, e.g. Blood clotting


positive and negative feedback

e)

Feedforward regulation

anticipates changes in a
regulated variable, improves the speed of the body's
homeostatic responses, and minimizes fluctuations
in the level of the variable being regulated

(1)

Involves an initial set of receptors, e.g., skin
thermal recep
tors then core thermal
receptors

(2)

Conditions the body for further adjustments

III.

Components of Homeostatic Systems

-

Text page 1
1

A.

Reflexes



genetically determined response to stimulus

1.

Stimulus
-
response sequen
ce

a)

Most are inborn, automatic and the individual is not
aware of their action, they are involuntary

b)

Others are learned or acquired like driving a car

2.

Components of reflex arc
, Figure
1
-
5
, page 1
2

a)

Recept
or

b)

Afferent pathway

(input)

c)

Integrating center

d)

Efferent pathway

(output)

e)

Effector

3.

Examples
-

Hypothermia, Figure
1
-
6
, page 1
2

4.

Questions about hom
eostatic reflexes
-

Table
1
-
3, page
13

(five questions)

a)

What parameter is being maintained?

b)

What are the afferent and efferent mechanisms?

c)

Where and what are the receptors?

d)

Where is the integrating center?

e)

What are the effectors?

B.

Local homeostatic response
s

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1.

Local means that the homeostatic mechanism doesn't
involve a long pathway or an integrating center

2.

Very important

3.

Provide individual areas of the body with mechanisms for
local self
-
regulation (local vasodilation)

C.

Intercellular
chemical messengers

1.

For reflexes to work internally there must be a mechanism
for relaying information such as hormones to its “
target
cell

1

2.

Neurotransmitters
, Figure
1
-
7
, page 1
4

a)

Means by which neurons communi
cate

b)

Chemicals that is secreted by neurons but enter the
blood stream are properly known as hormones or
neurohormones, NOT neurotransmitters

3.

Paracrine agents

(local hormones)

a)

Chemical messengers involved in local responses

b)

Paracrin
es effect cells close to themselves

4.

Chemical substances that are secondary by
-
products of
cellular activity can act as messengers

a)

They are not specific messengers as are paracrines,
hormones and neurotransmitters

b)

Examples: potassium
, hydr
ogen ion effects on
vascular smooth muscle

5.

Autocrines

-

A chemical secreted into the extracellular fluid
surrounding the cell and act upon the cell that secreted it

6.

These different substances can act in different modes
depending on the h
omeostatic mechanism in question, i.e.
somatostatin can act as hormone, paracrine (or autocrine) or
neurotransmitter

7.

Exceptions to circulating messengers

a)

Gap junctions

-

direct transfer of information

b)

Messenge
r may be embedded in plasma membrane
-

example is found in immune function

IV.

Processes Related to Homeostasis

A.

Adaptation &
Acclimatization

-

Text page 15

1.

All physiological homeostatic mechanisms are inherited

a)

Physiological mechanisms are developmentally
determin
ed and have critical periods

b)

Genetically determined as function as time

c)

Critical period

in during infancy and childhood and
developmental acclimatization

2.

There can be a wide variation of respons
iveness due to
"conditioning"


Andes Indians, eg.

B.

Biological rhythms

-

Text page 15




1
The term “target cell” is a misnomer and left over from before it was understood
how hormones act upon the appropriate cells
-

more later

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1.

Some homeostatic mechanisms operate on a cyclic basis,
i.e. menstrual cycle

2.

Innate such as
circadian

rhythm of body is 24 hours

a)

Entrainment

-

while rhythms are innate they can be
influenced by external factors

b)

Experiment with light cycle and free
-
running rhythms

c)

Studies on these cycles reveal much about work
shifts and “jet lag”

d)

See Figure
1
-
8
, page 153

3.

Neural basis of body rhy
thms?

a)

Hypothalamus



pacemaker nuclei not understood

b)

One output to pineal gland that secretes
melatonin


sleep cycle

c)

A “feedforward” mechanism working in concert with
homeostatic mechanisms

C.

Apoptosis

(regulated cell d
eath
) plays an important role in
homeostasis by helping to regulate cell numbers and eliminating
undesirable cells



Regulated Cell Death


1.

It is obvious that the proliferation and differentiation of cells
are important for the development and maintenance of
homeostasis in multicellular organisms.

2.

Virtually all cells have the ability to self
-
destruct by activation
of an

intrinsic

cell suicide program.

a)

This type of cell death, termed apoptosis, plays
important roles in the sculpting of a developing
organism and in the elimination of undesirable cells
(for example, cells that have become cancerous),
but it is particularly

crucial for regulating the
number
of cells

in a tissue or organ.

b)

A balance between cell proliferation and cell death
normally determines the control of cell number within
each cell lineage, both of which are regulated
processes. For example,
white blood c
ells

called
neutrophils are programmed to die by apoptosis 24
hours after they are produced in the bone marrow.

3.

Apoptosis occurs by controlled autodigestion of the cell
contents.

a)

Within a cell, endogenous enzymes are activated
that break down the cell nuc
leus and its DNA, as
well as other cell organelles. Importantly, the plasma
membrane is maintained as the cell dies so that the
cell contents are not dispersed. Instead the
apoptotic cell sends out chemical messengers that
attract neighboring phagocytic ce
lls (cells that "eat"
matter or other cells), which engulf and digest the
dying or dead cell. In this way the leakage of
breakdown products, many of which are toxic, from
apoptotic cells is prevented.

b)

Apoptosis is, therefore, very different from the death

of a cell due to externally imposed injury; in that
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case (termed necrosis) the plasma membrane is
disrupted, and the cell swells and releases its
cytoplasmic material, inducing an inflammatory
response, as described in Chapter 20.

4.

All normal cells contain

the enzymes capable of carrying out
apoptosis means that these enzymes must normally remain
inactive if the cell is to survive.

a)

In most tissues this inactivity is maintained by the
constant supply to the cell of a large number of
chemical "survival signa
ls" provided by neighboring
cells, hormones, and the extracellular matrix.

b)

In other words,
most cells are programmed to
commit suicide

if survival signals are not received
from the internal environment. For example,
prostate
-
gland cells undergo apoptosis w
hen the
influence on them of testosterone, the male sex
hormone, is removed. In addition, there are other
chemical signals, some exogenous to the organism
(for example, certain viruses and bacterial toxins)
and some endogenous (for example, certain
messeng
ers released by nerve cells and white blood
cells) that can inhibit or override survival signals and
induce the cell to undergo apoptosis.

5.

It is very likely that abnormal inhibition of appropriate
apoptosis may contribute to diseases, like cancer,
characte
rized by excessive numbers of cells.

a)

At the other end of the spectrum too high a rate of
apoptosis probably contributes to degenerative
diseases, such as that of bone in the disease called
osteoporosis.

b)

The hope is that therapies designed to enhance or
d
ecrease apoptosis, depending on the situation,
would ameliorate these diseases.

See box below for further explanation.

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Al
so called Programmed Cell Death,

in biology, a mechanism
that allows cells to self
-
destruct when stimulated by the appropriate trigge
r. Apoptosis is initiated for various
reasons, such as when a cell is no longer needed within the body or when it becomes a
threat to the health of the organism. Apoptosis is necessary in
embryon
ic development as
well as in the daily maintenance of a mature organism. The aberrant inhibition or initiation
of apoptosis contributes to many disease processes, including cancer .

Embryologists in the early 20th century were familiar with the process of

programmed cell
death. They observed that as an embryo develops, many of its cells are sacrificed to create
the final form of the organism. Not until 1972, however, did researchers John F.R. Kerr,
Andrew H. Wyllie, and Alastair Currie recognize the broade
r significance of this
mechanism. They coined the term
apoptosis

from the Greek word meaning “falling off,” as
leaves do in autumn, to describe this natural, timely death of cells.
Apoptosis

is
distinguished from an alternate form of cell death, called nec
rosis, that results from injury.


Apoptosis

is a normal physiological process that offsets cell proliferation. It is a genetically
programmed event that can be set in motion by a variety of internal or external stimuli. A
signal activates genes in the cell
's suicide pathway which encode the proteins that destroy
the cell's structural proteins and genetic material. A number of morphological changes
occur in the apoptotic cell

e.g.,

the cell begins to shrivel and pull away from other cells,
bubblelike formati
ons appear on its surface, and chromatin (chromosomal DNA and
protein) in the cell's nucleus condenses. The cell then either is consumed by other cells or
breaks up into smaller pieces that are engulfed by scavenger cells. Cells in virtually all
tissues ma
y be sacrificed through
apoptosis

for the good of the organism. For example,
the cells of the uterine wall undergo programmed death in the monthly menstrual cycle.


Various phenomena can disturb the regulation of the cell death pathway, causing too many
or

too few cells to die. Many types of disease result from such disruptions. If, for example, a
mutation occurs in a gene that induces
apoptosis
, such as the tumour
-
suppressor gene
p53, the cell that harbours the gene may fail to respond to the cue to die. A
s a result the
cell may proliferate uncontrollably and form a cancerous tumour. In other cases a virus may
interfere with the regulation of
apoptosis
, inducing healthy cells to die. This mechanism is
believed to play a role in
AIDS

, the disease in which infection with the HIV virus results in
the destruction of healthy white blood cells called T lymphocytes
.

"Apoptosis."

Encyclopædia Britannica
. 2003.


Encyclopædia Britannica Premium Service.

09
Aug, 2003

<
http://www.britannica.com/eb/article?eu=3035


D.

Aging and homeostasis

1.

Aging

is not a disease
-

it is the latter stages of development
and is gene
tically determined

2.

Development patterns

are NOT homeostatically controlled

3.

Homeostatic mechanisms don't operate as well
-

start
downhill at age thirty (30), that is the beginning of
senescence

4.

Aging is marked

by a loss of cells by the body


a
combination of less cell division and increased cell death

5.

Basis of senescence isn't understood

a)

Recent study shows that if the studies of the aged
are weighed in favor of those people who have not
abused themselves they
show much less decline in
abilities.

b)

Twin studies show about 1/3rd of aging is genetic
and the other 2/3rds environmental

c)

Non
-
human animal studies indicates that caloric
restriction can prolong the life span in rats

E.

Balance in the homeostasis of chemicals

1.

Figure 7
-
8, page 156
-

balance diagram

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a)

Net loss > net gain = negative balance

b)

Net loss < net gain = positive balance

c)

Net loss = net gain = stability

2.

Figure 7
-
9, page 157


shows adjustment to increase in
sodium setpoint but the net effect is 2% increase i
n sodium
levels because it is the net signal error