Chapter 1
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Human Physiology
Physiology:
study of how
body works to maintain life
Pathophysiology:
how
physiological processes are
altered in disease or injury
1-3
Homeostasis
1-9
Homeostasis
 Is
maintenance of a state of dynamic constancy
In which conditions are stabilized above and below
a physiological set point
By negative feedback loops
1-10
Negative Feedback Loops
Sensor:
Detects
deviation from set point
Integrating center:
Determines response
Effector: Produces
response
1-11
Homeostasis continued
 Regulatory
mechanisms:
Intrinsic control is built into
organ being regulated
1-12
Homeostasis continued
 Regulatory
mechanisms:
Extrinsic control comes from outside of organ
E.g. body temperature is controlled by
antagonistic effects of sweating and shivering
1-13
Homeostasis continued
 Regulatory
mechanisms:
Positive feedback is rare because it amplifies
changes
It is involved in producing blood clots
In females it is used to create the LH surge that
causes ovulation
Positive feedback between the uterus and
oxytocin secretion occurs during labor
1-15
Negative Feedback Hormonal Control of
Blood Glucose
1-17
Chapter 3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Gene Expression
3-26
Gene Expression
Genes
are lengths of DNA that code for
synthesis of RNA
mRNA carries info for how to make a protein
Is transported out of nucleus to ribosomes
where proteins are made
3-27
Gene Expression continued
Takes
place in 2 stages:
Transcription occurs when DNA sequence in
a gene is turned into a mRNA sequence
Translation occurs when mRNA sequence is
used to make a protein
3-28
Gene Expression continued
Each
nucleus contains 1 or more dark areas
called nucleoli
These contain genes actively making rRNA
3-29
Genome and Proteome
Genome
refers to all genes in an individual or
in a species
Proteome refers to all proteins produced by a
genome
3-30
Chromatin
 Is
made of DNA and its associated proteins (=histones)
 Histones are positively charged and form spools around which
negatively charged DNA strands wrap
 Each spool and its DNA is called a nucleosome
3-31
Chromatin continued
Euchromatin
is the part of chromosomes active
in transcription
Light in color
Heterochromatin is highly condensed region
where genes are permanently inactivated
3-32
Chromatin continued
3-33
RNA Synthesis
One
gene is several thousand nucleotide pairs
long
DNA in a human cell contains over 3 billion
base pairs
This is enough to code for at least 3 million
proteins
But, only a fraction of DNA used for proteins
Rest is redundant or may be inactive
3-34
RNA Synthesis continued
For
transcription, RNA polymerase binds to a
“start” sequence on DNA and unzips strands
Nearby are promoter regions, which regulate
levels of transcription
Transcription factors must bind to promoter
to initiate transcription
3-35
RNA Synthesis continued
 Only
one strand of DNA
contains the gene and is
transcribed
 Its bases pair with
complementary RNA
bases to make mRNA
 G pairs with C
 A pairs with U
 RNA polymerase
detaches when hits a
"stop" sequence
3-36
RNA Synthesis continued
Transcription
produces four types of RNA:
pre-mRNA - altered in nucleus to form mRNA
mRNA - contains the code for synthesis of a
protein
tRNA (transfer RNA) - decodes the info
contained in mRNA
rRNA - forms part of ribosomes
3-37
RNA Synthesis continued
 Pre-mRNA
is much larger
than mRNA
 Contains non-coding
regions called introns
 Coding regions are called
exons
 In nucleus, introns are
removed and ends of
exons spliced together to
produce final mRNA
3-38
RNA Synthesis continued
Human
genome has <25,000 genes
Yet produces >100,000 different proteins
1 gene codes for an average of 3 different
proteins
Accomplished by alternative splicing of
exons
 This allows a given gene to produce
several different mRNAs
3-39
RNA Synthesis continued
A
newly discovered type of RNA is involved in
regulating gene expression
These perform RNA interference (RNAi) or silencing
Interfere with or silence expression of some
genes
siRNA (short interfering RNA) and miRNA (micro
RNA) molecules pair in varying degrees with
different mRNAs
Thereby interfering with expression of those
mRNAs
1 miRNA may interfere with up to 200 different
mRNAs
3-40
Protein Synthesis
Occurs
one amino acid at a time according to
sequence of base triplets in mRNA
In cytoplasm, mRNA attaches to ribosomes
forming a polysome where translation occurs
3-41
Protein Synthesis continued
 Ribosomes
read 3 mRNA bases (= a triplet) at a time
 Each triplet is a codon, which specifies an amino acid
 Ribosomes translate codons into an amino acid sequence
that becomes a polypeptide chain
3-42
Protein Synthesis continued
3-43
Protein Synthesis continued
 Translation
of codons is
achieved by tRNA and
enzymes
 tRNA contains 3 loops,
one of which contains an
anticodon
 Which is
complementary to a
specific mRNA codon
 Each tRNA carries the
amino acid specified
by its anticodon
3-44
Protein Synthesis continued
 In
a ribosome, anticodons on tRNA bind to mRNA codons
 Amino acids on adjacent tRNAs are brought together and linked
enzymatically by peptide bonds
 This forms a polypeptide; at a stop codon it detaches from
ribosome
3-45
Functions of ER
Proteins
to be secreted are made in ribosomes of
rough ER
Contain a leader sequence of 30+ hydrophobic
amino acids that directs such proteins to enter
cisternae of ER
Where leader sequence is removed; protein is
modified
3-46
Functions of Golgi
Secretory
proteins leave ER in vesicles and go
to Golgi
In the Golgi complex carbohydrates are
added to make glycoproteins
Vesicles leave Golgi for lysosomes or
exocytosis
3-47
Protein Degradation
The
activity of many enzymes and regulatory
proteins is controlled by rapidly degrading them
By proteases in lysosomes
And by cytoplasmic proteasomes
3-48
Chapter 6
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Transport Across Plasma
Membrane
Plasma
membrane is selectively permeable-allows only certain kinds of molecules to pass
Many important molecules have transporters
and channels
Carrier-mediated transport involves specific
protein transporters
Non-carrier mediated transport occurs by
diffusion
6-7
Transport Across Plasma
Membrane continued
Passive
transport moves compounds down
concentration gradient; requires no energy
Active transport moves compounds against a
concentration gradient; requires energy and
transporters
6-8
Diffusion
Is
random motion of molecules
Net movement is from region of high to low
concentration
6-9
Diffusion continued
Non-polar
compounds readily diffuse thru cell
membrane
Also some small molecules such as CO2 and
H 2O
Gas exchange occurs this way
6-10
Diffusion continued
Cell
membranes are
impermeable to
charged and most
polar compounds
Charged
molecules must
have an ion
channel or
transporter to
move across
membrane
6-11
Diffusion continued
Rate
of diffusion of a compound depends on:
Magnitude of its concentration gradient
Permeability of membrane to it
Temperature
Surface area of membrane
6-12
Osmosis
6-13
Osmosis
 Is
net diffusion of H2O across a
selectively permeable membrane
 H2O diffuses down its
concentration gradient
 H2O is less concentrated
where there are more solutes
 Solutes have to be
osmotically active
 i.e., cannot freely move
across membrane
6-14
Osmosis continued
H2O
diffuses down its concentration gradient
until its concentration is equal on both sides
of a membrane
Some cells have water channels (aquaporins)
to facilitate osmosis
6-15
Osmotic Pressure
Is
the force that would have to be exerted to
stop osmosis
Indicates how strongly H2O wants to diffuse
Is proportional to solute concentration
6-16
Molarity and Molality
1
molar solution (1.0M) = 1 mole of solute
dissolved in 1L of solution
Doesn't specify exact amount of H2O
1 molal solution (1.0m) = 1 mole of solute
dissolved in 1 kg H2O
6-17
Molarity and Molality continued
Osmolality
(Osm)
is total molality of a
solution
e.g., 1.0m of
NaCl yields a 2
Osm solution
Because NaCl
dissociates into
Na+ and Cl-
6-18
Tonicity
Is
the effect of a solution on osmotic movement of H2O
Isotonic solutions have same osmotic pressure
Hypertonic solutions have higher osmotic pressure
and are osmotically active
Hypotonics have lower osmotic pressure
Isosmotic solutions have same osmolality as plasma
Hypo-osmotic solutions have lower osmotic pressure
than plasma
 Hyperosmotics have higher pressure than plasma
6-19
6-20
Regulation of Blood Osmolality
Blood
osmolality is
maintained in narrow
range around 300mOsm
If dehydration occurs,
osmoreceptors in
hypothalamus stimulate:
ADH release
Which causes
kidney to conserve
H2O and thirst
6-21
Membrane Transport
Systems
6-22
Carrier-Mediated Transport
Molecules
too large and polar to diffuse are
transported across membrane by protein
carriers
6-23
Carrier-Mediated Transport continued
 Protein
carriers exhibit:
 Specificity for single
molecule
 Competition among
substrates for
transport
 Saturation when all
carriers are occupied
This is called Tm
(transport
maximum)
6-24
Facilitated Diffusion
Is
passive transport down concentration
gradient by carrier proteins
6-25
An Active Transport Pump
Is
transport of
molecules against a
concentration
gradient
ATP is required
A carrier protein
is required
6-26
Na+/K+ Pump
Uses
ATP to move
3 Na+ out and 2 K+
in
Against their
gradients
6-27
Secondary Active Transport
ATP
needed for “uphill” (against the
concentration gradient) movement of molecule
or ion obtained from “downhill” (with the
concentration gradient) transport of Na+ into cell
6-28
Secondary Active Transport continued
Cotransport
(symport) is secondary transport in
same direction as Na+
Countertransport (antiport) moves molecule in
opposite direction to Na+
6-29
Transport Across Epithelial
Membranes
 Absorption
is
transport of
digestion products
across intestinal
epithelium into
blood
 Reabsorption
transports
compounds out of
urinary filtrate
back into blood
6-30
Transport Across Epithelial
Membranes continued
Transcellular
transport moves material from 1
side to other of epithelial cells
Paracellular transport moves material through
tiny spaces between epithelial cells
6-31
Transport Across Epithelial
Membranes continued
Transport
between cells is limited by junctional
complexes that connect adjacent epithelial cells
6-32
Transport Across Epithelial
Membranes continued
 Plasma
membranes
can join together to
form tight junctions
 In adherens junctions
membranes are
“glued” together by
proteins that pass
through both
membranes and
attach to
cytoskeletons
 In desmosomes
proteins “button” two
membranes together
6-33
Bulk Transport
Moves
large molecules and particles across
plasma membrane
Occurs by endocytosis and exocytosis (Ch 3)
6-34
Membrane Potential
6-35
Membrane Potential
 Is
difference in charge
across membranes
 Results in part from
presence of large anions
being trapped inside cell
 Diffusable cations
such as K+ are
attracted into cell by
anions
 Na+ is not permeable
and is actively
transported out
6-36
Equilibrium Potential
 Describes
voltage across cell membrane if only 1 ion could
diffuse
 If membrane permeable only
to K+, it would diffuse until it
reaches its equilibrium
potential (Ek)
 K+ is attracted inside by
trapped anions but also
driven out by its
concentration gradient
 At K+ equilibrium,
electrical and diffusion
forces are = and opposite
 Inside of cell has a
negative charge of about 90mV
6-37
Nernst Equation (Ex)
Gives
membrane voltage needed to counteract
concentration forces acting on an ion
Value of Ex depends on ratio of ion
concentrations inside and outside cell
membrane
Ex = 61 log [Xout]
z
[Xin]
Z = valence of the ion
6-38
Nernst Equation (Ex) continued
 Ex
= 61 log [Xout]
z
[Xin]
 For
concentrations
shown at right:
 Calculate EK+
 Calculate ENa+
6-39
Nernst Equation (Ex) continued
 EK+
= 61 log 5
+1 150
= -90mV
 ENa+
= 61 log 145
+1
12
= +66mV
6-40
Resting Membrane Potential (RMP)
Is
membrane voltage of cell not producing
impulses
RMP of most cells is –65 to –85 mV
RMP depends on concentrations of ions inside
and out
And on permeability of each ion
Affected most by K+ because it is most
permeable
6-41
Resting Membrane Potential (RMP)
continued
Na+
diffuses in so
RMP is less
negative than
EK+
Some
6-42
Role of Na+/K+ Pumps in RMP
Because
3 Na+ are pumped out for every 2
K+ taken in, pump is electrogenic
It adds about
–3mV to RMP
6-43
Summary of Processes that Affect the
Resting Membrane Potential
6-44