Nursing 3366 Pathologic Processes: Implications for Nursing (ONLINE COURSE)
REQUIRED READING DOCUMENT #1
1
Basic Concepts, Genetic Influence in Disease, and Intracellular Function and
Disorders
Instructions:
1.
Read this entire RRD (Required Reading Document) and other documents
mentioned.
2.
Work on Assignment #1 and submit by designated deadline.
Note about objectives /outcomes and studying for this course:
For ALL content in this course, the student will be able to DESCRIBE/DISCUSS/IDENTIFY
correlations (links) between pathophysiology of the disease and its clinical manifestations. In
other words, #1: how does the pathophysiology of a particular disease cause the signs and
symptoms, and #2: if a patient presents the signs and symptoms of a disease, be able to use
critical thinking to figure out the disease process that is most likely in that context.
Basic Concepts of Pathophysiology & Implications for Nursing
Objectives /outcomes
DESCRIBE/DISCUSS/IDENTIFY:
1. concepts underlying the nomenclature of physiology and pathophysiology.
2. appropriate, general application of those concepts to disease processes and situations.
Re: sidebar & other boxed info in all your notes:
a. Information in a sidebar box is added knowledge for you, or a
Outline for Lecture:
review of
I.
Overview
previous info or sometimes some A&P info, etc
b. If the info in the box is prefaced by “FYI,” you won’t be
A.
Physiology
responsible
B.
Pathophysiology
for it on a test.
C.
Examples
c. If there is no “FYI” preface, the information IS eligible for test
II.
Some basic physiologic concepts.
Some standard language usage
A.
Homeostasis
clarifications:
o “AKA” means “also known
B.
Compensation and decompensation
as.”
III.
Pathophysiologic concepts & terminology
o “IE” or “ie” means “in other
A.
Disease vs disorder vs syndrome
words.”
o “eg” means “for example.”
B.
Terms relating to elements leading up to a disease
o this sign before a word
C.
Terms relating to causes of a disease
means “approximately:” ~
D.
Terms relating to course of a disease
E.
Sequela: aftermath of a disease
________________________________
I.
Overview
A.
Physiology-study of functions & processes that occur in body,
mostly the NORMAL
processes
B.
Pathophysiology -- the study of the underlying changes in body physiology
that
result from disease or injury
FYI: pathology & pathophysiology come
from Latin root word “pathos”—suffering.)
C.
Examples:
1.
physiologic amenorrhea (menstrual flow ceases because of
menopause, pregnancy, etc) versus pathophysiological amenorrhea
(menstrual flow ceases because of cancer, for ex.)
2.
physiologic albuminuria versus pathophysiological albuminuria
II.
Some basic physiologic concepts.
A.
2
Homeostasis—maintenance of constant conditions in the body’s internal
environment
1.
Cells must have constant supply of nutrients, H2O, O2, and exist in
narrow
pH & temperature range
2.
Maintaining homeostasis is essentially a balancing act-- the body is
always trying to “right itself” when homeostasis is
challenged by changes.
3.
These challenges to the body’s balance are sometimes called
stressors.
B.
Compensation and decompensation
1.
The return to homeostasis after being challenged by a stressor is
called
compensation; similar words are adaptation, healing,
etc.
a.
Compensation is achieved by the body’s use of control
mechanisms, also called compensatory mechanisms.
b.
Control / compensatory mechanisms examples:
1)
Example of compensatory response to “normal” dailylife stressors: if you run out of available glucose
between meals & can’t eat immediately, your body
turns to the “back-up” system of glycogenolysis —
breakdown of glycogen, which is a form of stored
glucose.
2)
Example of compensatory response to pathologic
stressors: if
you’ve lost a lot of blood (massive bleeding) or water
(dehydration), the body uses certain compensatory
techniques to keep remaining fluid volume circulating as
effectively as possible (temporary measures until the
cause of the problem gets fixed) :
a)
heart rate would increase to get blood around
faster to
temporarily make up for loss of volume.
b)
also, arteries in your periphery (arms and legs)
would
constrict, shunting whatever blood volume is left
to the central areas, that is, to your most
important organs—brain, heart, lungs, kidneys.
Other examples of compensatory mechanisms:
o If there is too much CO2 in your body for some reason, control mechanisms in the respiratory centers of the
brain increase respiratory rate so that CO2 exhalation is increased.
o If you have too much blood volume or the pressure in your arteries is too high over a long period of time:
1) the heart will need to pump with more force to eject blood into your arteries.
2) to do this, it will have to “shore up” its muscle-- this is called muscle hypertrophy: the heart muscle
compensates for the
extra stressors by undergoing hypertrophy.
o Checks and balances example:
1) part of the inflammatory response to a cut on the toe is to begin the clotting process
2) if the clotting process continued indefinitely, the whole body would be one big clot
3) so, the fibrinolytic system that dismantles a clot is the “check and balance” to the clotting process
4) summary: control mechanism to bleeding = clotting; “check” to the clotting = fibrinolytic system.
2.
If the body is unable to appropriately meet the challenge of
stressors-- for example, if the control mechanisms are
“exhausted”-- compensation can deteriorate either rapidly or
slowly into decompensation— the failure to compensate, adapt,
heal, etc.
III.
to
3
Pathophysiologic concepts & terminology
A.
Disease vs disorder vs syndrome
1.
a disease is a harmful condition of the body (and/or mind); a
disorder is a disturbance in the healthiness of the body; a syndrome
is a collection of symptoms
2.
for this class these terms will be basically interchangeable, as they
all are a disturbance in body homeostasis; most of the time I will
use the term disease (or abbreviate as “dz.”)
B.
Terms relating to elements leading up to a disease
1.
risk factors
a.
factors that or contribute to and/or increase probability that a
dz will occur …”setting the stage”
b.
ex-- heredity, age, ethnicity, lifestyle (smoking, eating habits,
etc), environment
2.
precipitating factor
a.
a condition or event that triggers a pathologic event or
disorder ….
the “kick-off”
b.
ex—“an asthma attack can be precipitated by exertion”
C.
Terms relating to causes of a disease
1.
etiology-- the cause of a disease; includes all factors that contribute
development
of dz; examples:
a.
etiology of AIDS: HIV (human immunodeficiency virus)
b.
etiology of rheumatic heart disease: autoimmune reaction
c.
TB (tuberculosis): mycobacterium
3.
idiopathic—dz with unidentifiable cause
4.
iatrogenic problem -- occurs as result of medical treatment
 ex—if kidney failure is due to improper use of antibiotics
prescribed by a healthcare provider you could say “the
etiology of the kidney failure was iatrogenic.”
5.
nosocomial problems—result as consequence of being in hospital
environment

ex— urinary tract infection is called a nosocomial infection if
it developed while patient was in the hospital.
D.
Terms relating to course of a disease
1.
Clinical manifestations (ie, S&S)-- the demonstration of the
presence of a
sign and/or symptom of a disease
a.
signs-- manifestations that can be objectively identified by a
trained
observer
b.
symptoms -- subjective manifestations that can only be
reported by
the person experiencing them-- pain, nausea, fatigue
4
(***note, most often on a patient chart, “signs and symptoms” appear as “S & S”
or S/S; also, often in medical vernacular, “symptoms” is used as a shortcut instead
of saying “signs and symptoms.”)
c.
malaise (“I
d.
insidious and
local versus systemic S&S:
1)
some S&S are local:
redness, swelling, heat, rash, &
lymphadenopathy in a particular area
2)
others are systemic, such as fever, urticaria (hives),
feel dragged out” or “awful all over”), systemic
lymphadenopathy
acuity and timing of S&S
1)
acute S&S:
a)
fairly rapid appearance of S&S of dz (over a day to
several days); usually last only a short time
 ex: “The patient had an acute URI (upper
respiratory infection) that resolved within a
few days.”
b)
also can mean increase in severity
 ex: “The acuity of the patient’s URI
increased and he had to be hospitalized.”
2)
chronic S&S —develop more slowly; S&S are often
last longer and/or wax and wane over months or years.
a)
remissions—periods when S&S disappear or
diminish
significantly (wane)
exacerbations—periods when S&S become worse
or more severe (wax); exacerbate—to provoke, to
make worse.
 ex: “The patient had an exacerbation of his
chronic asthma and had to go to the
hospital.”
terms relating to location of manifestations:
1)
central
a)
usually refers to problem, situation, etc, that is
towards the center, or “core,” of the body
b)
often used when referring to essential organ
b)
e.
occurring
systems
c)
like brain, heart, lungs, kidneys;
 ex— when someone loses a lot of blood, the
body shunts most of the remaining blood
away from non-essential areas such as gut,
hands, feet, so that the essential organs are
oxygenated—ie, most of the volume of
blood ends up circulating centrally.
the more central an area or problem is, the more
proximal to the core it is;
 ex—“the arm was fractured proximal to the
elbow.”
 this means a break between elbow &
shoulder
2)
peripheral, or periphery
a)
refers to problem, situation, etc, that is occurring
towards the outer parts of the body, away from
core
i.
ex—if we lose a lot of blood, the blood
Basic definition
vessels of
of “shock:”
low BP plus S&S
of not getting
enough blood to
different parts
of the body (ex
—confusion
from not getting
blood to brain).
ii.
iii.
b)
further
2.
the
D.
degrees of
valve.
the periphery often constrict so that not a
lot of blood can circulate into those areas
(mainly arms & legs)
thus there is more blood going to central
areas such as the heart, brain, lungs, and
kidneys—blood has been shunted to those
areas
this is why sometimes a sign of shock is
cool, pale extremities.
the more peripheral an area or problem is, or
away from the core of the body, the more distal it
is
 ex—“distal to the blood clot in the left
coronary artery, the tissue lost oxygenation
& died.”
Prognosis-- the predicted outcome of a dz based on certain factors:
a.
the usual course of that particular dz
b.
individual’s characteristics; ex:
1)
age: patients at either end of age spectrum --infants &
elderly are at higher risk for a poor prognosis due to
immature or “worn out” immune systems, respectively.
2)
presence of comorbidities– two or more coexisting
medical conditions; this increases chance of poor
prognosis
 ex—“The patient’s comorbidities of heart
disease and lung disease contributed to his
poor prognosis in recovering from
pneumonia.”
_sequela (plural: sequelae): aftermath of a disease
1.
a sequela is any abnormal condition that follows and is the result of
disease, injury, or treatment; synonym = complications
2.
occasionally the term is used as simply “outcome,” such as: “A
positive
3.
5
sequela of getting pneumonia was that the patient stopped
smoking;” but most of time “sequela” is used with a negative
connotation.
severity of sequela varies; examples of sequelae with various
seriousness:
a.
sequela of rheumatic fever can sometimes be a bad heart
b.
possible sequela of chicken pox scarring
c.
possible sequela of stroke weakness on one side of the
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body
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Here is a partial list of terms to look over to make sure you understand them (other terms may come
up that you will need to look up as well). Many should be familiar from A&P. YOU WON’T BE
SPECIFICALLY TESTED ON THESE, but they will help you parse out word meanings.
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a/an – prefix meaning not, without
ab- prefix meaning from, away from, off
ad- prefix meaning increase, adherence, to or toward
aer- prefix meaning the air, or gas
algia- suffix referring to pain or painful condition
ascend- to move upward to a higher position
asymmetrical –denoting a lack of symmetry between two or more parts that are alike
bi- prefix meaning twice or double
bilateral- relating to or having two sides
blast- denotes an immature precursor cell
brady- prefix meaning slow
dorsal- pertaining to the back
dys- prefix referring to “bad” or difficulty
ectomy- suffix denoting removal of an anatomical part
emia- suffix meaning “in the blood”
hemo- prefix referring to blood
hemorrhage- escape of blood from the intravascular space. To bleed.
hyper- prefix meaning excessive, above normal
hypo-prefix deficient, below normal
ICU- IntensiveCare Unit
“i” – suffix that often creates plural form; ex—one embolus, two emboli.
iasis—suffix meaning state or condition.
idio- prefix meaning private, distinctive, or peculiar to.
inferior- situated below or directly downward
itis – suffix meaning having to do with inflammation or infection
IV- intravenous
lipo – pertaining to fat
lytic- suffix creates adjective form of lysis
lysis- suffix refers to destruction of a substances, usually a cell
macro- prefix meaning large, long
megaly- suffix meaning large
micro- prefix denoting smallness
necro-prefix meaning death
ostomy- suffix meaning artificial opening (stoma) into the urinary or gastrointestinal tract or trachea
ology- suffix meaning the study of a subject
osis—suffix meaning condition
otomy- suffix meaning a cutting operation
plasty- suffix referring to molding, shaping or the result there of a surgical procedure.
scopy- suffix referring to viewing or seeing
superior- situated above or directly upward
symmetrical- equality in two like parts
tachy- prefix meaning rapid
unilateral- confined to one side of the body only
ventral – pertaining to the front side (as opposed to dorsal)
VS—vital signs:
o BP—blood pressure (measured as systolic over diastolic mm of Hg)
o HR—heart rate (measured in beats per minute).
o RR—respiratory rate (breaths per minute)
o T or temp—temperature.
o SO2 or pulse oximeter or pulse ox or O2 sat—oxygen saturation (measured as percentage—we will
go into this more in a later lecture)
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ALSO, VERY IMPORTANT!! FOR EACH SET OF READINGS, MAKE YOUR OWN VOCABULARY LIST FOR
YOUR OWN STUDY BENEFIT. For this set of readings only, I made a list to give you an example. (In any set of
readings, if there are words that I have not explained, and that you do not know, look them up in your book or
a medical dictionary and/or ask me about them. You will be responsible for all vocabulary. NOTE:
7
vocabulary of basic concepts will be used throughout the semester in other readings and on tests, so BE SURE to
get familiar with them.

physiologic

pathologic
See last couple of pages of “How
remission

homeostasis
Manual” if you would like to know how

exacerbation

compensation
to do a “flashcard concept map.” The

central

decompensation

peripheral
emphasis in doing flashcards this new

etiology

proximal
way is to realize that knowing a word

risk factors

distal
and its definition (rote memorization) is

prognosis

etiology
not enough—you must understand its

comorbidity

precipitating
CONTEXT. That’s what gives it true

sequela
factor

acute / acuity
meaning & application potential.

idiopathic

chronic

iatrogenic

nosocomial
______________________________________________________________________________________________
Genetic Influence in Disease
Objectives /outcomes
DESCRIBE/DISCUSS/IDENTIFY:
 various multifactorial genetic disorders
 pathophysiology of basic chromosomal problems such as Down’s syndrome & the
Philadelphia chromosome
 single-gene alterations resulting in protein synthesis defects and their relationship
to disease processes & symptoms, such as sickle cell anemia, polycystic kidney
disease, &, hemophilia
 some therapeutic uses of recombinant DNA.
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~~~
NOTE: Here between the wavy lines is a little A&P background (a very brief review about
what you should already have learned in A&P [see the Prep & ch 2 in book if you need more
A&P]… this first part won’t be on a test per se, but it is important foundation for patho info.)
1.
Gene definition and function
a.
Definition of a gene--a segment of a DNA molecule that is composed of
an
ordered sequence of nucleotide bases (adenine, guanine, cytosine,
thymine)
b.
Main functions of genes: coding for synthesis of proteins that form our
traits and
functional characteristics.
1)
Examples of these include “permanent” proteins such as eye
pigment, hair
color,
and blood type in a developing fetus, as well
as more subtle inherited
traits like outgoing personality or
susceptibility to certain diseases.
2)
There are also “day-to-day” functional proteins such as hormones,
antigens, antibodies, enzymes, etc.
c.
When there is a mutation of a gene, the protein it is responsible for often
malfunctions.
1)
You can have a pretty good idea of what type of disorder & S&S
occur when
you understand this pathologic process.
2)
Ex—if the gene that codes for lactase becomes mutated, lactase
cannot properly breakdown and process lactose. Lactose ingestion
then causes diarrhea. This is called lactose intolerance.
2.
Packaging of genes: chromosomes
8
a.
The DNA helix containing genes goes through many shapes during the
cell life but
at one point takes the shape that we are most familiar with– the
rod-shaped body
in the nucleus of cells called a chromosome.
1)
To summarize: a sequence of nucleotide bases forms a gene;
genes make
up a DNA molecule, and that DNA molecule forms into a
specialized
shape called a chromosome
2)
A chromosome can be thought of (very simplistically) as a string of
multipurpose beads, with the beads being genes.
b.
A person receives 23 chromosomes from each parent, so you end up
with 23 pairs, or a total of 46.
1)
22 pairs are autosomal– ie, NOT sex chromosomes– and each pair is
closely alike.
2)
The other pair is the sex chromosomes– XX or XY.
3)
For purposes of study they can be arranged in a karyotype (a
picture)
ex— chromosome #1 from mom is matched up with
chromosome #1 from
dad.
c.
Autosomal chromosome pairs (#1-22).
1)
For these pairs, each has genes that closely match “partners” on
the
other chromosome.
2)
Partner genes have the same location (“locus”) on each respective
chromosome, code for the same trait, and are called “a
pair of alleles.”
3)
A pair of alleles are almost exactly alike except that one can be
dominant &
one can be recessive (or they can both be dominant or
both be recessive).
4)
We notate recessive genes with a lower-case letter & a dominant
gene as
an upper-case letter.
a)
The combinations are called genotypes & represent what was
inherited from mom & dad.
b)
Examples of various combinations (randomly using the letter
“g”), can
be GG (homozygous dominant); gg (homozygous recessive);
Gg
(heterozygous).
d.
There is one pair of sex chromosomes (#23) which work very differently.
There is info on them & on sex-linked disorders later in these notes, but
you won’t be tested on that info.
e.
If a geneticist is trying to figure out the percent chance of two people with
certain
genotypes having a child with certain genetic characteristics, a
Punnett square is
often used. (Note: you must understand & be able
to do Punnett squares for the
exam).
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Outline for Reading & Studying Genetic Influence in Disease:
A.
B.
Overview
1.
definition of genetic disorders
2.
categorizing genetic disorders
3.
mitochondrial DNA disorders
4.
multifactorial
5.
chromosomal
6.
single-gene
Single-gene disorders
linked
1.
overview/ categories: autosomal recessive, autosomal dominant, sex-
2.
autosomal recessive
a.
overview
b.
example of autosomal recessive disorder--sickle cell anemia
autosomal dominant
a.
overview
b.
example of autosomal dominant disorder—polycystic kidney
3.
disease
C.
9
4.
sex-linked—example is hemophilia
Recombinant DNA– a form of genetic engineering
A.
Overview
1.
broad definition of “genetic disorders”-- a disease caused by
abnormalities in an
individual’s genetic material
2.
there are several ways of categorizing genetic disorders:
a.
inherited vs “spontaneous”
Some
1)
example of inherited disorders—sickle cell disease is caused
explanations of
by an inherited, altered (AKA, “mutated”) gene (see below)
terms:
2)
example of spontaneous—high level of exposure to radiation
“Environmental”
causes
a
is used here to
mutation in a gene becomes an “oncogene” which causes
mean any
influence other
rapid, wild proliferation of cell growth skin cancer develops.
than inherited.
b.
other ways to categorize include using the following four groupings:
“Onco” prefix
disorders of mitochondrial DNA, multifactorial, chromosomal, singlemeans “cancergene.
3.
mitochondrial DNA disorders
a.
majority of DNA is found in nucleus of cells but small bits of DNA are
also found in mitochondria
b.
disorders of this DNA are very uncommon & won’t be discussed
4.
multifactorial genetic disorders -- combination of environmental triggers
and variations / mutations of genes, plus sometimes inherited tendencies;
examples:
a.
various cancers such as lung cancer: begins by smoke & toxins
irritating bronchial tissue one or more genes in cells of that tissue
begin to be deranged—oncogenes created  code for wild,
uncontrolled growth of cells.
b.
many common diseases such as hypertension (HTN), coronary
artery disease (CAD) & diabetes mellitus (DM) are now known to be
caused or highly influenced by a mix of environmental and inherited
components.
c.
teratogenic disorders:
1)
a teratogen is any influence — eg, drugs, radiation, viruses-that can cause congenital defects
2)
congenital defects are abnormalities that are either
detectable at birth and/or can be attributed to fetal
development “glitches.”
3)
so “teratogenic disorders” and “congenital defects” are
virtually interchangeable terms
4)
specific examples:
here
a)
b)
fetal alcohol syndrome (FAS) occurs because toxicity
of alcohol causes gene mutations during gestational
development.
“thalidomide babies” – born with abnormal arms and
legs due to mothers taking the drug thalidomide for
nausea during early pregnancy.
10
5.
chromosomal disorders (AKA, chromosomal aberrations)
a.
definition-- a type of genetic disorder that results from alterations to
the numbers or structure of a chromosome, which in turn alters the
“local” genes (genes in the immediate area)--the genes’
FYI: chromosomal
disorders occur in ~1%
functionality is disrupted and they don’t code proteins correctly,
of live births (2% for
giving rise to the phenotype (S&S) of the disorder.
women older than 35
years) & are leading
b.
alteration to NUMBERS of chromosomes is called an aneuploidy.
known cause of mental
retardation &
1)
aneuploidies have the suffix “somy;” for instance, a generic
miscarriage--about 50%
of all recovered firstterm for “more than usual numbers of chromosomes” would
semester spontaneous
be polysomy-- Down’s syndrome is an example of a polysomy
abortions (miscarriages)
have major
2)
Down’s is a disorder of abnormal numbers of chromosomes
chromosome
abnormalities that
that is sometimes associated with pregnancies of women >35
years old.
3)
it is a “glitch” that occurs in very early cellular division and
chromosomal distribution of a fertilized egg: instead of ending
up with the normal number--46 chromosomes-- the fetus ends
up with 47
4)
the extra chromosome occurs at site #21 -- the 21st
chromosome set has three chromosomes instead of two.
Putting things together: One of
the subcategories of
a)
thus the other name for this type of Down’s is trisomy
chromosomal disorders is
21.
aneuploidy. Trisomy 21
(Down’s) is a polysomic
b)
phenotype of trisomy 21 includes mental retardation
aneuploidy. Did you understand
and typical physical characteristics such as low-set ears,
that?
epicanthic fold to the eyes, short limbs, and a largerthan-normal tongue.
c.
example of alterations to STRUCTURE of chromosomes—
Philadelphia chromosome
1)
some types of chromosomal aberrations are caused by
alterations in chromosomal structure, such as deletion,
duplication, or rearrangement of gene sites (translocation) on
the chromosome
2)
an example of this is the Philadelphia chromosome, which
results from translocation & will be discussed further in
another set of readings.
6.
B.
single-gene disorders – discussed below….
Single-gene disorders FYI: there are more than 6,000 known single-gene disorders, which
occur in about 1 out of every 200 births.
1.
overview
a.
single-gene disorders are usually due to an inherited mutated gene
b.
since genes code for proteins, when a gene mutates so that its
protein
product can no longer carry out its normal function, a
disorder can result.
c.
autosomal
single-gene disorders are inherited in recognizable patterns:
recessive, autosomal dominant, and sex-linked.
11
2.
autosomal recessive disorder
a.
overview
1)
an autosomal recessive disorder occurs when a mutated
(“diseased”),
recessive (“weak”) gene partners up with an
FYI:
other examples:
phenylketonuria
allele that is also
recessive & diseased; those alleles are
(PKU), cystic fibrosis,
notated with two lower-case
letters.
Tay-Sachs disease,
2)
the
protein
that
they
code
for will then malfunction & an
Wilson’s disease, and
many
more.
abnormality/
disease/ disorder will occur that relates to that
“bad”
protein
b.
example of autosomal recessive disorder--sickle cell anemia
1)
genotype and patho development
a)
at a certain locus on a certain pair of chromosomes, a
pair
alleles has the job of coding for the creation of
KEY toof
drawings:
= mutated gene
normally shaped
hemoglobin (Hgb)
b)
but if during fertilization a person inherits a sickle-cell
= normal gene
disease
gene from mom – ie, a recessive, mutated Hgb-coding
gene – and ALSO inherits a sickle-cell disease gene from
s
s
dad:
(1)
this person would have a homozygous genotype
of the
recessive sickle cell genes: ss
Remember:
When assigning notations for autosomal recessive diseases, the “big”
letter will be the dominant, normal, non-diseased allele, and the “little” letter will be
the diseased allele.
(2)
The suffix “emia” means “in the blood.”
Anemia literally means “no blood,” but
in actuality it is used to mean “there
are less-than-normal numbers of RBCs
in the blood.”
disease
2)
(3)
those abnormal recessive alleles will code for
abnormally-shaped Hgb (sickle-shaped), which will
make the RBCs sickle-shaped (there are ~300 Hgb
molecules per RBC, so enough sickled Hgbs in an
RBC will deform the RBC too)
because these RBCs do not have the usual round
& smooth shape, they are more easily damaged
as they go through the blood stream; ultimately
this results in less-than-normal numbers of RBCs—
this is the definition of
anemia.
phenotype—a person who has an ss genotype will HAVE the
sickle cell anemia—ie, their phenotype is having the S&S
caused by the above genotype and patho development:
If cells are not getting enough
oxygen and it is due to a
circulatory malfunction, the
problem is called ischemia.
Pain in the tissue that is not
getting enough oxygen is
called ischemic pain.
a)
SOB (shortness of breath), weakness & fatigue due to
decreased O2 being carried to tissues of the body; this
decreased carrying capacity is because of:
(1)
anemia: less numbers of RBCs to carry the Hgb
which in turn carries the O2
12
(2)
(WHEN YOU ARE
STUDYING MATERIAL IN
THIS COURSE, BE SURE
TO KNOW HOW TO LINK
S&S TO THE PATHO OF
THE DISEASE & VICE
VERSA; this section is
good example of being
able to do that.)
3)
disease gene
gene from the other
would be: _Ss_
deformed Hgb simply cannot carry the usual
numbers of O2 molecules
b)
ischemic pain, especially in the joints; patho of this type
of pain:
(1)
the deformed RBCs “clog” up the capillaries that
usually carry O2-rich blood to the tissues
(2)
this results in distal tissues that are starved to O2
& “cry out” in pain.
other combinations of alleles
a)
if during fertilization a person inherits a sickle-cell
from one parent but a normal Hgb-coding
parent, the person’s genotype for Hgb
b)
anemia” &
dominant over the
will NOT have the disease
to offspring.
carrier.
the
“having the
has the genotype
cell disease.)
c)
we call this a “heterozygous genotype for sickle cell
we know that because the NORMAL gene is
sickle-cell recessive gene, the person
but they may pass on the gene
(1)
this is called being a carrier; so Ss is a sickle cell
(2)
rarely, a carrier will have a milder phenotype of
disease—ie, mild S&S; this situation is called
trait.” (Someone with sickle cell trait
Ss but has mild S&S of sickle
someone with the genotype SS doesn’t have to worry
about
either having the disease or passing it on—
they are what is
called “homozygous normal.”
3.
autosomal dominant disorders
a.
overview
1)
occurs when a person inherits a mutated, diseased gene that
is
dominant
2)
ie, the gene that codes for a certain disease characteristic is
dominant, and the gene that codes for the normal
characteristic is recessive (exactly opposite of autosomal
recessive)
b.
example of autosomal dominant disorder—polycystic kidney
disease
(PKD)
FYI: other examples:
1)
genotype & patho development
Huntington’s
a)
at a certain locus on a certain pair of chromosomes, a
disease
neurofibromatosis,
pair of
alleles has the job of coding for the creation of
Marfan’s syndrome
normal kidney
tissue
When assigning
b)
if during fertilization a person inherits a kidney tissue
notations for autosomal
gene
that has a mutation, that gene will “want” to code
dominant diseases, the
for
abnormal
kidneys.
“big” letter
will be the
c)
in a dominant disease such as PKD, the mutated gene is
dominant, diseased
allele, and the “little”
the
strong one, so even if it is paired with a normal
letter will
be the normal,
allele,
it will
override the normal allele’s coding.
non- diseased allele.
d)
cysts,
2)
see if you can draw & label all 3
for
possible allele pairing combinations
for this
autosomal
dominant
this:
PP or
Pp.
disorder; I will start you with just
plain circles and you can fill in “P”
or “p”…. Then think: will this person
HAVE the disease or not?
3)
in PKD, this results in the kidney tissue developing
13
which
can reduces various kidney functions and
lead to kidney failure as a person goes through life.
genotype notation
a)
if we use the letter “P” to designate PKD, the genotype
someone that HAS the disease would look like
b)
only a person with a genotype of pp
(homozygous recessive) would NOT have the disease
or
or
S&S
a)
hematuria (blood in urine), proteinuria, frequent kidney
infections
b)
pain at costovertebral angles and abdomen
c)
kidney stones
4.
sex-linked disorders
a.
normal physiology of sex chromosomes:
When assigning
1)
The two X’s in a woman work just like autosomal
notations for Xlinked recessive
chromosomes – a gene on one X has a partner allele at the
diseases, use
same locus on the other X that usually code for the same
XX for women
& XY for men.
trait.
Then attach
2)
But in a male the genes on his X have no comparable partner
letters to the
X’s.
allele on his Y.
The “big” letter
3)
We notate these as such: Xl Xl (homozygous female); XL Xl
will be
dominant,
(heterozygous female); Xl Y or XL Y for the male.
normal, nonb.
types
of sex-linked disorders:
diseased
allele, and the
1)
possibilities include X-linked dominant, X-linked recessive, & Y“little” letter
linked.
2)
X-linked dominant and any kind of Y-linked diseases are
will be the
rare—sexlinked diseases most commonly fall under X-linked
recessive
3)
therefore “X-linked” and “sex-linked” terminologies are often
interchanged, and when someone says “sex-linked,”
they often mean
“X-linked recessive.”
c.
X-linked recessive diseases are caused by a recessive allele that is
always
located only on an X chromosome
1)
in most cases, a female who has the diseased recessive gene
on one
of her X chromosomes is protected by a normal
dominant gene on
her other X chromosome, so a female
will rarely have an X-linked
disease—she will only be a
carrier
2)
but a male who gets an X chromosome with the diseased
gene will
not have a matching normal gene on another X
FYI: Other
chromosome, because
he only has a Y chromosome
examples include
3)
therefore,
the
phenotype
of most X-linked disorders is usually
certain types of
muscular dystrophy.
expressed in male offspring.
d.
example of sex-linked disorder—hemophilia
1)
there are several types of hemophilia, each caused by
different
gene mutations on the X chromosome.
14
2)
normally the genes code for one of the coagulation factors
that
facilitates normal clotting when there is an injury;
examples—Factor
XIII & Factor IX.
3)
if one of these genes mutates, it may code for a defective
coagulation factor, resulting in altered ability to clot.
4)
because the hemophilia gene is an X-linked gene, the
genotype for
someone that has the disease would
look like this: Xh Y; genotypes
of Xh XH, XH XH, or XH Y would
not have the disease
***In each category of autosomal dominant, autosomal recessive, and sex-linked disorders, be sure you
are able to figure out the percent chance of two people with certain genotypes having children with
varying genotypes & possible phenotypes – do this with Punnett squares.
C.
Recombinant DNA– a form of genetic engineering
1.
many alterations in DNA came about as a natural part of evolution, but
now we can
deliberately alter DNA in the interests of medicine and
science.
2.
recombinant DNA is a “new” DNA that results from purposefully
combining two or
more different sources of DNA; ex-- altering
(“engineering”) DNA codons in bacteria
to make proteins the bacteria would
not ordinarily produce
3.
current applications of this process:
a.
human growth hormone for children lacking it.
b.
exogenous (“from outside the body”) insulin for diabetics.
c.
factor VIII for hemophiliacs.
d.
drugs like tPA & tenecteplase—given as “clot-buster” in patients
having MI (an MI, a myocardial infarction is when a clot develops in
a coronary artery & blocks blood flow to the distal tissue, which
begins to die… thus if a drug can get rid of the clot, flow will be
restored & tissue will be saved.)
__________________________________________________________________________
Intracellular Functions and Disorders
Objectives /outcomes
DESCRIBE/DISCUSS/IDENTIFY:
1. normal cellular metabolism and its alternate states, including anaerobic metabolism and the
processes of glycogenesis, glycogenolysis, and gluconeogenesis.
2. the effect of alterations of key molecular substances such as sodium, potassium, and calcium on
electrical properties of cells.
3. the relationship of all the above to certain disease processes and signs and symptoms (S&S),
including:
 hypoxic states
 alterations of glucose availability.
 alterations in usage of certain vitamins.
 hyperpolarized and hypopolarized plasma membranes.
4.
basic states of acidosis and alkalosis & how the body compensates.
Outline for Intracellular Functions and Disorders
15
I.
Overview
IMPORTANT NOTE: As you come across various numbers in your
A.
Alterations in cellular-level functionreading, be aware that very few of them will need to be
memorized. Exceptions include numbers that I feel will be very
B.
Etiology of these disruptions
useful to know in your nursing practice. Those numbers I will
II.
Hypoxia’s effect on cellular-level functionindicate with wordage such as “know now and forever.” That
means they may come up again at any time in the semester and
A.
Overview of hypoxia
you will STILL need to know them. Please feel free to ask me
B.
Sequelae of hypoxia
about this issue and any other.
III.
Effect of nutritional alterations on cellular-level function.
A.
Overview
B.
A review of NORMAL glucose use and back-up systems
C.
Examples of disease processes related to cellular metabolism “back-up plans”
D.
Examples of other disorders that can contribute to disruption in metabolic
pathway
IV.
Alterations in solute status
This is A&P review info & won’t be
A.
A&P overview of select solutes
as such. However,
B.
A&P overview of normal electrical function of cellstested
understanding it is CRUCIAL to
C.
A&P overview of body fluid compartments
understanding the patho.
D.
Cellular electrical problems secondary to alterations in electrolyte balance
E.
Acid / base sequelae of solute imbalance, ie, acid / base imbalance
~~~~~~~~~~~~
I.
Overview
A.
Again, please review and understand the concept map
“THE METABOLIC PATHWAY & DISTURBANCES.”
Alterations in cellular-level function
1.
Many normal daily changes in body homeostasis can affect the
metabolic pathway (upon which we depend for energy in the form of
ATP), and usually the body can adjust & maintain equilibrium—sort
of an ongoing “fine-tuning.”
2.
But there are also problems that more seriously disrupt homeostasis
of cellular metabolism and the provision of ATP for body needs; it is
more difficult for the body to adjust & return to equilibrium in these
cases.
3.
Many of the disorders & disease processes that we will study in this
course either CAUSE or are CAUSED BY some sort of cellular-level
disruption that eventually leads to decrease in ATP.
B.
Etiology of these disruptions include:
1.
hypoxia —decrease in amount of oxygen to cell or ability to use
oxygen
appropriately (part II)
2.
nutritional problems such as decreased glucose & vitamin
availability for cell use (part III)
3.
changes in balance of electrolytes & other solutes, including
acid/base
imbalance (part IV)
4
changes in fluid distribution (this will be discussed in RRD 4).
FYI: All of above imbalances rarely “stand alone”—usually one abnormality triggers another; ex: a
bacteria causes disturbance in permeability of lung cells’ plasma membrane there is pathological
influx of water into cells causes swelling in organelles such as mitochondria interrupts electron
transport chain functioning no ATPs to fuel energy needs of lung cells breathing is
compromised hypoxia (diminished O2 to cells) reliance on glycolysis lactic acidosis further
disturbance in function of lung cells & other cells of body (body’s cells “hate” acidosis!) etc.
II.
Hypoxia (decrease in oxygen)—effect on cellular-level function
A.
simply
Overview of hypoxia: has a spectrum of etiology and seriousness: from
overworked muscles in extreme exercise (the muscles use up
16
immediate available
oxygen), to someone who is having difficulty
breathing & therefore cannot
get enough oxygen to the heart to circulate
it to the tissues, to someone
whose artery in the arm is cut, so the
tissues distal to the trauma cannot get
oxygen, and so on.
B.
Sequelae of hypoxia (see page 2 of concept map)
1.
if there is hypoxia:
a.
cellular metabolism has to “recycle” through glycolysis rather
than
continue down the usual aerobic pathway
Aerobic–
b.
this
is
because glycolysis is the only step that can operate
O2 is present
(this
is
the
under
normal, aerobic conditions, AND can also operate
ideal, “normal”
under
anaerobic
conditions
situation).
positive side to anaerobic glycolysis:
Anaerobic– low 2.
or absent O2.
a.
it can give 2 molecules of ATP per molecule of glucose to give
energy
to the cell.
b.
thus, it is a temporary stop-gap measure that keeps your body
going
until the cells can get more O2 so that aerobic
metabolism
can
be
reestablished.
acidosis—a state
of greater-than3.
negative side to anaerobic glycolysis:
usual
a.
2 molecule of ATP is not enough to keep going for a long time.
concentration of
acidic
b.
also, every time the metabolic process must “recycle” through
substances in
glycolysis, multiple molecules of pyruvate (pyruvic acid)
the blood and
accumulate,
resulting in acidosis.
4.
summary: two main sequela result from hypoxia:
Key physiologic principle:
a.
The byproducts of the
body’s normal metabolic
activities are slightly more
electrical
cell
acidic
than alkaline.
To
counteract
that
acidic
electrical impulses will
tendency, the body “likes”
b.
to keep a very narrow and
slightly alkaline pH range of
the blood—
7.35 to 7.45 (Know
this range “now &
5.
deficiency of ATP for cellular functions; ex—without ATP, the
Na / K pump of each cell cannot maintain normal
membrane status and propagation of
be
disrupted.
altered acid/ base balance, especially acidosis; significance:
acidosis from something like hypoxia or reliance on
gluconeogenesis (more on this in next section) can
dangerously tip body pH out of its narrow, desirable range
fairly quickly
all the above can cause damage and death to tissues (more on
“altered tissue” in another RRD).
refer to concept map
III.
Effect of nutritional alterations on cellular-level function.
A.
Overview
1.
cells have certain nutritional needs to carry on normal metabolic
function
a.
glucose is obtained from carbohydrates to begin the cellular
metabolic
pathway that leads to energy provision in the form of
ATPs
b.
vitamins (and other substances) provide the “support staff”
for the metabolic pathway.
2.
process of glucose access & usage depends on cellular metabolic
needs at any given moment.
B.
A review of NORMAL glucose use and back-up systems:
17
1.
if you have just eaten, glucose in the blood normally goes up, a
Glycogen is a large
molecule thatstate
is too of
temporary hyperglycemia; this triggers the pancreas to
big to be used for
secrete
insulin
energy as it is, but
when necessary it
to circulate to cells and assist in getting glucose molecules from the
can be stimulated
blood
to break down into
small glucose
into the cells to use as the main source of cellular energy.
molecules that can
2.
if intake of food / glucose is greater than immediate cellular energy
be used more
effectively.
Think
needs,
of it as “stored
insulin directs the excess glucose to be stored as glycogen_ in the
glucose.”
liver. This is called _glycogenesis (genesis = “creation of”).
The processes above are considered to be “regulatory:” insulin triggers regulatory,
“building up” processes of 1) glucose entering cells, & 2) the creation of glycogen
3.(glycogenesis).
later, if you don’t eat and / or the availability of glucose is less than
cellular
sugar)usually exists.
a.
triggered
3)
4)
energy needs, a state of _hypoglycemia (low blood
certain hormones called the counterregulatory hormones are
by low blood glucose:
AKA, stress hormones
1)
epinephrine from the adrenal medulla
because hypoglycemia is
stressful for the body, so
2)
cortisol from the adrenal cortex
they come “to the
growth hormone (GH) from the pituitary rescue.”.
glucagon from the pancreas.
b.
roles of these hormones include:
1)
“alarms”—sensations of hunger, shakiness, sweating,
irritability
—these are telling you to “EAT!”
BACK UP
PLAN
2)
if you don’t eat, the body takes the first step in its “back-up
#1:
plan:” the counterregulatory hormones stimulate
Glycogenolysis
the conversion
of glycogen to glucose.
a)
this process is called glycogenolysis (lysis =
“breakdown”) &
results in a higher blood sugar, correcting the
hypoglycemia &
making glucose available to the cells for energy use.
b)
many times a day if our body needs some glucose & we
cannot immediately take it orally, glycogenolysis
takes
place as a “stop gap measure” till we can
take in glucose.
c.
the next step in body’s normal “back-up plan”
1)
if glucose is either unavailable or cannot get into the cell to
BACK UP
participate
in the
metabolic pathway, and glycogenolysis has
PLAN
#2:
already exhausted a
person’s store of glycogen, the body breaks
Gluconeoge
down fats and protein.
nesis
2)
this is called gluconeogenesis--the use of any other substance
besides carbohydrates for cellular energy; this means
breaking down fats and proteins for energy.
3)
one of the breakdown products of fats and proteins is ketones
a)
“good” characteristic of ketones: they can offer the
FYI: 3 main ketones:
body some energy—usually enough to be a “stop gap”
a) acetoacetic acid
b) beta-hydroxybutyric
till glucose is available.
acid
b)
two “bad” characteristics of ketones:
c) acetone (another acid)
(1)
they are acids-- over time there is a danger of
acidosis
(2)
they can’t be used by brain cells—brain cells
MUST have glucose for energy.
18
***If you’ve ever felt dizzy, dull-witted or cognitively challenged when hypoglycemic, it’s because your brain cells are
ESPECIALLY reliant on glucose for energy. If brain cells are deprived of glucose, they can become electrically disturbed and a
person can become unconscious, have a seizure, and / or even die. Clinical significance: Often when a patient presents with
an altered level of consciousness, one of the first things we do is test the blood sugar.
Summary: Glycogenolysis & gluconeogenesis are considered to be “breaking-down,”
“counterregulatory” processes triggered by the counterregulatory hormones when
hypoglycemia is present.
C.
Examples of disease processes related to cellular metabolism “back-up plans”
1.
glycogen storage diseases -- abnormalities in glycogenesis or
glycogenolysis
a.
ex-- McArdle’s disease—an autosomal recessive
disease in which
which normal ability to breakdown glycogen
(glycogenolysis) is diminished.
b.
S&S that might occur in a person with this kind of disease-muscle
weakness & cramps during exercise because of no
energy reserves.
2.
Type I diabetes: gluconeogenesis taken to extreme: (gluconeogenesis is
normal
body back-up process, but if disease process alters it or
causes sustained usage,
then has potentially detrimental
consequences)
a.
people with Type I diabetes mellitus do not make insulin
without insulin, glucose unable to get into cells, glycogen is
eventually used
up, (so BACK-UP PLAN #1 is used up), and body
turns to sustained
gluconeogenesis (BACK-UP PLAN #2) as its
main energy pathway.
b.
this is ok for awhile, but eventually sustained gluconeogenesis
causes
ketone over-accumulation, resulting in hyperketonemia
(high levels of
ketones in the blood)
c.
FYI: Of course, a
diabetic would also have
high serum glucose (no
insulin = no ability to
move be
glucose
from
called
bloodstream into cells =
hyperglycemia) and
glucosuria (glucose
spilling into urine), but
urine);
right now
we are just
discussing
hyperketonemia —the
“downside” of sustained
hyperketonemia is manifested by:
1)
blood test showing high serum ketones.
2)
AND usually the following as well:
a)
blood test showing LOW (<7.35) blood pH—this would
ketoacidosis—a form of acidosis;
and/or
b)
urine test which shows ketonuria (ketones spill into
and/or
c)
S&S such as acetone breath (excretion via lungs).
D.
Examples of other disorders / problems that can contribute to disruption in
metabolic pathway:
1.
alterations in vitamin & mineral access or usage
a.
overview
1)
glucose begins the metabolic pathway, but certain other
FYI—dietary iron can be
obtained in liver, molecules
salmon, beans, eggs;
thiamine is in lean
meats, fish, milk. Also
many of our grocery
19
such as vitamins & minerals are necessary to maximize the
creation of ATP—they are nutrients of which we need only
small amounts but which are crucial to our bodies’ well-being
[as can be seen in concept map, page 2…niacin (B3),
thiamine (B1), riboflavin (B2); iron (Fe).]
2)
in most cases sufficient amounts cannot be made by our
bodies and must be supplied by diet.
3)
in underdeveloped countries, vitamin deficiencies are often
due to complete lack of availability of certain foods; in U.S.,
vitamin deficiencies occur usually as a result of poor dietary
habits or chronic disease
b.
example of a type of patient that nurses often see who would be
high risk for vitamin deficiencies: an alcoholic.
1)
often an alcoholic has very poor diet—obtains minimal iron
and B vitamins such as thiamine (as well as countless other
deficiencies)
2)
as a sequela of iron deficiency, may develop iron-deficiency
anemia; seeing iron’s role in the metabolic pathway, what
kinds of S&S do you think might this patient have? (S&S
related to low ATP & low oxygenation—weakness, fatigue
SOB),
3)
thiamine deficiency is called beriberi & sequelae include
neuro problems:
a)
because B1 is particularly important in the functioning
CLARIFICATION: Beriberi is
the disease name of general
of neurologic cells (including brain tissue), many S&S of
thiamine deficiency.
depletion of this vitamin (& other B vitamins) show up
Wernicke-Korsakoff
syndrome is a group of
as neurologic problems
neurologic S&S especially
b)
examples of neurologic issues associated with thiamine
seen in alcoholics with
deficiency:
(1)
Wernicke-Korsakoff syndrome – classically
associated with alcoholism and manifested as
paresthesia--“pins &
needles” feeling (like when
memory loss and ataxia (staggering,
your foot falls asleep &
uncoordinated gait)
“wakes up”)
(2)
paresthesia--numbness & tingling or other
unusual sensations, usually in legs (this is seen in
B12 deficiency too).
2.
various drugs, both medicinal & street drugs.
3.
poisons; ex—cyanide
a.
cyanide present in insecticides, rodenticides, metal polishes,
FYI—when I make long
lists like this, it is not
burning
wool
&
silk, certain drugs such as nitroprusside; now
always important to
memorize the items
considered potential
bioterrorism drug.
specifically… most of
them time it is a certain
b.
S&S
of
toxicity
include
headache,
agitation,
confusion, vomiting,
concept that I want you
to “get”… if you have
eventually
respiratory problems & death.
questions about what to
know for a test in a
c.
mechanism
of action-- inhibits cytochrome oxidase (look on
“listing” case like this,
concept map)
IV.
Alterations in solute status
***Before getting into the alterations in solute status, carefully look over the following info (sections A, B, & C,
between the dotted lines below)—this is A&P stuff, not tested per se, but you still must have a good grasp of it to
understand the patho material.***
20
A.
A&P overview of select solutes (solute are molecules that have been dissolved in a fluid—in this case in
the fluid of the blood, which is mostly water)
1.
proteins
a.
found:
1)
in the plasma; examples: albumin and lipoproteins.
2)
in the cells—proteins are abundant intracellular anions
b.
a few of their most important functions are:
1)
helping with electrical balance across cell membrane.
.
2)
helping with fluid compartment balance; this is especially true of albumin, which is
the
most abundant protein in the plasma.
3)
serving in many other roles such as immunoglobulins (antibodies) and as
coagulation
factors such as prothrombin, thrombin, etc
3.
glucose—common solute in the blood & cells; important for energy, but also can cause fluid shifts.
4.
electrolytes (electrolytes are molecules that, once in fluid, separate into charged atoms called
ions)
a
sodium-- Na+:
1)
the most abundant cation in extracellular fluids
2)
the key electrolyte that drives water movement—generally speaking,
“where Na+ goes, H2O follows”
3)
most often travels in the blood as sodium chloride—NaCl
b
chloride--Cl-: also tends to “follow” Na—they easily form a bond and usually
travel together in the bloodstream as NaCl until they get to cells, where they
dissociate
in order to go in and out of cell membrane ion channels.
c.
potassium-- K+: the main cation in the intracellular fluid; one of most important functions
balance Na+
1)
the kidneys use Na & K to offset each other in the process of maintaining
is to
homeostasis
a)
ex--if there is not enough Na and / or water in the body, aldosterone is
by the adrenal gland--this stimulates the kidneys to “hold
b)
the opposite happens if we need to “hold on” to K or if we need to get rid
secreted
on” to Na and excrete K
of Na.
2)
also, the Na / K pump keep Na & K in the ratios needed to drive appropriate cell
membrane electrical impulse propagation
a)
Na/K “pumps” are part of cell membranes and pump out 3 Na ions for
every 2
K ions that come into cell—ie, because more cations are
being pumped out than
are staying inside, the inside of the cell is
slightly negative with respect to the
outside.
b)
this is what keeps the cell membrane slightly & confers a resting
membrane
potential (RMP) of ~ -90mV to most cell membranes
d.
calcium-- Ca+:
1)
a cation that has many important uses in the body, including:
a)
Ca+ is an important part of muscle cell contraction; ex-(1)
it affects the normal entrance of Na into the cells
(2)
effect on Na+ is an inverse one:
--less calcium in the body more Na will go into cell.
--more calcium less Na will go into cell
b)
Ca+ is one of the factors needed to clot blood properly
c)
also has great importance in bone growth & maintenance.
2)
regulated by activation of vitamin D, by PTH (parathyroid hormone), and by the
kidneys.
e.
phosphorous-- usually exists as phosphate-- PO4- :
1)
the main intracellular anion
2)
balances Ca+ --generally, when one is high, the other is low.
f.
important ions / molecules in acid/base balance:
1)
the “acid gang:” hydrogen—H+ & carbon dioxide-- CO2
2)
the “alkali guy:” bicarbonate--HCO3-.
B.
A&P overview of normal electrical function of cells –
again, carefully look over the info
in this box during your pre-lecture notes review as well info in Prep #2—we will go over this “normal
electrical function” material only briefly in class, and you MUST understand it in order to understand the
patho
1)
normal resting membrane potential (RMP) of most cells is about -90mv; it is negative because
in the resting state of a cell there are slightly more anions than cations inside the cell
membrane.
2)
normal depolarization point (point at which cell contracts) for most cells is about +30mv
3)
consider these numbers as a “normal” polar status
4)
think of the term “polar” as two points that are “apart”— one point is the RMP of -90 and
one point is the “goal” of the cell—to reach +30, the point at which it can contract
21
This is the blood flowing in capillaries throughout tissue. It has a certain
number-- “normal” – of electrolyte levels (ie, normal balance of cations &
anions).
This represents a single cell of
the tissues. K+, Na+ are
cations (I randomly put 5 of
them inside the cell). The
anions inside the cell are
represented by DASHES and
there are six of them.
5)
K+ K+ K+ Na+
Na+
------
Normal balance of tissue cell cations & anions …
note that there are normally more anions than
cations inside the cell, giving the RMP its normal
negative charge.
-90mv (normal RMP…the
resting state of the cell)
When an electrical signal reaches the resting cell,
it changes the balance of cations & anions in the
cell—
more cations flood the cell. This increases the
positivity of the cell membrane until it reaches ~
+30 mV. This is the “goal charge” for cell
membranes to achieve in order to depolarize
(contract).
+ 30 mV (normal depolarization
point—the contraction point-- the
cell can now contract-- “go to
work”)
K+ K+ K+ Na+
Na+
_____
This lightning bolt represents
an electrical signal coming
from a nerve or previous cell
that increases flow of cations
into “our” representative
cell, thus changing the
membrane charge from
to +30mV.
C.-90mVA&P
of body fluid
1.
the fluid)
Cations like Na+
flood into cell &
begin changing
90mV to a more
positive charge; ie,
compartments [NOTE:
basically
“fluid”
-90 starts
becoming
more positive
2 basic fluid compartments—extracellular
& intracellular
a.
Normal “POLAR GAP
STATUS”..
The dotted line arrow
stands for the
distance from the
RMP (one pole) to its
“goal charge” of
+30mV (the other
pole). It must reach
-90mv
this charge of +30 so
(normal
that the cell can
depolarize (contract)
RMP)
—“go to work”.
When there is a
normal RMP of
around -90mV, there
is a “normal” distance
translates to “water”]
to +30mV – ie, a
“normal” polar gap.
intracellular fluid compartment is the fluid-filled space inside cells (solutes are dissolved in
extracellular compartment has 2 components:
1)
the interstitial fluid compartment—fluid-filled space between cells and blood
vessels (solutes
are dissolved in the fluid)
2)
the plasma fluid compartment
a)
this is the fluid-filled space between the walls of blood vessels; we tend to
talk about this compartment as THE BLOOD
b)
however, there are several other commonly used terms for the plasma
compartment, besides “the blood,” which YOU MUST UNDERSTAND: the
main ones are vasculature, bloodstream, “in the vascular system,”
“in the blood vessels,” “in the circulatory system,” “blood
volume,” plasma, blood, circulation
2.
Solute movement and fluid shifts:
a.
as explained above, there are 3 fluid compartments; however in the clinical setting, we
tend to think in terms of the compartments most relevant to us, to how we view our
patients.
b.
for instance, though cells & interstitial spaces are separate compartments, we often lump
them together and call it “TISSUE.” Example: If the blood is diluted with extra
water, fluid moves from the plasma space to the interstitial space & eventually into the
cells. But often a short cut is used in talking about this phenomenon: I will often say “fluid
moves from the blood to the tissue.”
c.
so whether talking about solute diffusion or fluid shifts, think in terms of two compartments
involved in the “action:” BLOOD (“B” for short in the notes) and TISSUE (“T”).
d.
THE PATHO OF FLUID SHIFTS WILL BE DISCUSSE MORE IN RR #2.
D.
b.
Cellular electrical problems secondary to alterations in electrolyte balance
1.
overview
22
a.
before discussing specific pathologic electrical changes in cells,
let’s look at how electrolyte balance in the body compartments gets
“altered” in the first place to result in electrical pathologies:
1)
homeostasis, or balance, of solutes in the body means there
are
approximately the same sum of ions & other solutes
inside each fluid
compartment compared to the compartment “next door.”
2)
so if there is an alteration in the solution composition in one
compartment, a domino effect begins—diffusion of the solute
Remember that
solute molecules
particles results in changes in the next compartment, then the
usually follow the
next, etc. (This occurs because the body is always striving to
property of diffusion
—they want to go to a
return to a normal, even, homeostatic composition of solutes
compartment where
in each compartment.)
there are LESS
particles.
3)
as a general rule (and for simplicity purposes in this class)
ALWAYS think of these changes in solute & fluid balance as
occurring first in the plasma compartment (ie, blood, “B”),
then spreading to the tissue (interstitial fluid & cells-- “T”).
4)
or in
the changes / imbalances exist until the body can “right” itself
some cases, get medical intervention as needed.
b.
specific example of “domino effect” of solute shifts from
compartment
to compartment (this is a therapeutic example,
not a pathologic one, but the
same fundamental principle applies to any situation):
1)
if a person is taking potassium (K+) pills, the pills are digested
and then absorbed into the blood vessels in the lining of the
stomach and duodenum
Here’s what I mean
2)
then the K+ enters into the blood stream and increases the K+
by the change
occurring FIRST in the
level there—in a sense, this creates an electrolyte imbalance,
blood compartment…
since now there is more K+ in one compartment (the blood)
than usual.
3)
as the blood (with its now more-than-normal-number of K+)
circulates to various tissues, the K+ will eventually diffuse
INTO the tissue, because initially the tissue held a LESSER
number of K+ than the changed blood.
c.
for simplicity sake, we will discuss only cation movement between
blood and tissue; the particular cations & related
terminology are:
a.
potassium (K+); higher-than-normal numbers of K in blood is
called
hyperkalemia; lower-than-normal numbers of K in blood is
called hypokalemia.
b.
sodium (Na+); high Na+ = hypernatremia; low =
hyponatremia.
c.
calcium (Ca+); high Ca+ = hypercalcemia; low =
hypocalcemia.
2.
how electrolyte imbalances change electrical status of cells
as noted in the A&P section (pg 7 of these notes) “normal”
electrical status exists when there is a normal distance-- ie normal
“polar gap status”-- between the two poles of:
#1-- the RMP of ~90mV (when a cell is “resting” between each of
its contractions, the charge on its membrane is -90mV).
#2-- the “goal” charge of +30mV (the charge usually needed in
order for a cell to contract to “go to work,” do its “job;” that
job depends on what kind of cell it is—cardiomyocyte, deltoid
muscle cell, eyelid muscle cell, brain cells, etc)
b.
if, however, a disorder/disease/situation disrupts the normal balance
of electrolytes in the blood, eventually the balance of cations &
anions in the tissue cells will be affected
SEE
PODCAST –
it will help
you
visualize
2)
23
a.
1)
this causes a resetting of the cells’ resting membrane
potential (RMP) to a more positive number or a less positive
number
if the RMP is reset to a MORE positive
number than normal, it will shorten
the polar status —this is called
hypopolarization
3.
increased
3)
if the RMP is reset to a LESS positive
number than normal, it will lengthen the
polar status—this is called
hyperpolarization
HYPOPOLARIZED states: situations in which membranes of cells have
been reset to a MORE positive number than normal, shortening the polar
gap status & making them more sensitive
a.
examples of states in which cells become hypopolarized:
hyperkalemia,
hypernatremia, hypocalcemia
b.
mechanisms of action:
1)
hyperkalemia & hypernatremia are easy to understand: more
cations in the blood mean that eventually more cations will
diffuse from blood into cells
a)
within the cell, this creates a more “positive” state, ie,
positivity since more cations have moved in
b)
so instead of the usual RMP of -90mV, the cell
membrane is RESET to more positive RMP
c)
for instance it might increase its positivity to -60 mV;
the polar gap has shortened now (-60 is closer to
+30mV than -90 was) and we say the cell is
HYPOpolarized.
d)
now, when stimulated by an incoming electrical signal,
there is less distance for the cells’ charge to get to the
depolarization point (ie, to contract)
e)
the cell is now much more sensitive than normal and
will “go to work” (contract) quicker.
So remember:
hypocalcemia has
the peculiar
property of causing
more Na+ to go INTO
cells, so that cells
have abnormally
MORE cations inside
them
hypopolarized.
2)
hypocalcemia is a little harder to understand:
a)
the very presence of low calcium levels in the blood as
the blood circulates in tissue beds triggers an INCREASE
in permeability of cell membranes to Na+ so that MORE
Na+ is allowed INTO the cell than normal
b)
so now the situation is exactly like any other in which
there are more cations entering the cell  increased
cations in cell =
increased positivity (decreased negativity)=
_hypopolarization.
c.
S&S of hypopolarization:
1)
pathologic hypopolarization of cells manifests clinically as
muscles that
are too sensitive – ie, hyperactive, “irritable”
2)
they contract with smaller-than-normal stimulation, often
resulting in muscle tics or spasms (example—positive
Chvostek’s sign)
24
http://www.youtube.com/watch?v=cQ-xMeNAqys-- example of Chvostek’s: When the cheek is touched,
the cells of the muscles and nerves in the area HYPERreact, are HYPERsensitive, due to the HYPOpolarization
from problems such as hyperkalemia, hypernatremia, and especially HYPOcalcemia. The cheek involuntarily
contracts.
tetany.
3)
if the spasms are severe and/or unrelenting, this is called
**** increased positivity = hypopolarization (shortened polar gap) = hyperactivity of
cells****
4.
HYPERPOLARIZED states: situations in which membranes of cells have
been reset to a LESS positive number than normal, lengthening the polar
gap status & making them less sensitive
a.
examples of states in which cells become hyperpolarized:
hypokalemia,
hyponatremia, hypercalcemia
b.
mechanisms of action:
1)
hypokalemia & hyponatremia are easy to understand: less
cations in the blood mean that eventually more cations will
diffuse out of the cells into the blood
a)
within the cell, this creates a LESS “positive” state, ie,
decreased positivity, since more cations have moved
out.
b)
so instead of the usual RMP of -90mV, the cell
membrane is RESET to less positive RMP
c)
for instance it might decrease its positivity to -120 mV;
the polar gap has lengthened now (-120 is further from
+30mV than -90 was) and we say the cell is
HYPERpolarized.
d)
now, when stimulated by an incoming electrical signal,
there is more distance for the cells’ charge to get to
the depolarization point (ie, to contract)
e)
the cell is now much less sensitive than normal and it
will take longer for it to “go to work” (contract).
2)
hypercalcemia (like hypocalcemia) is a little harder to
understand:
a)
the very presence of high calcium levels in the blood as
the blood circulates in tissue beds triggers an
DECREASE in permeability of cell membranes to Na+ so
that LESS Na+ is allowed INTO the cell than normal
b)
so now the situation is exactly like any other in which
there are more cations LEAVING the cell  decreased
cations in cell = decreased positivity =
hyperpolarization.
c.
S&S of hyperpolarization:
1)
pathologic hyperpolarization of cells manifests clinically as
muscles that
are less sensitive than usual– ie, hypoactive.
2)
they contract more slowly, often resulting in patients
complaining of fatigue, lethargy, mental slowness.
25
**** decreased positivity = hyperpolarization (lengthened polar gap) = hypoactivity of
cells****
Summary: When given a solute-change situation, this is what should go on in your mind:
1.
I have been given a scenario in which there is a change in solute composition of the body and must
figure out how
that affects cellular electrical status.
2.
The first thing I must do is figure out what has happened in the blood—are there now MORE solutes
or LESS in the blood now?
3..
Based on the change above, and the process of diffusion: When the blood circulates to the tissue, will
solutes go
from blood to tissue or tissue to blood?
4.
Let’s assume the solutes are cations …. If diffusion takes them from B to T: they will be making cells
more
electrically positive than normal …If diffusion takes them from T to B, then the cells will become LESS
positive.
Going further: when trying to figure out whether a cell has become hypopolarized or hyperpolarized, ask
yourself:
1.
As a result of a disorder & resultant diffusion, are there now MORE cations than usual in the cell or
LESS than
usual?
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
~~~~~~~~
IMPORTANT INFO ABOUT ABGS:
o
o
“ABGs” stands for arterial blood gases—a measurement of oxygenation & acid/base balance in the blood.
Some of the measurements are indeed actually “gases”—PCO2, PO2 in particular. But for now we will be
concentrating on metabolic issues that focus on two measurements that aren’t gases: pH & HCO3
--pH is a measurement of “how acidic is this person?” The LOWER the pH, the more acidic the person’s blood
is.
The HGHER the pH, the more alkali the person’s blood is. The acidity of someone’s blood reflects in general
how acidic the rest of the body is—other fluids, cells, etc.
-- HCO3 is the chemical name for bicarbonate.
Here are some principles to remember (see also, ABGs chart):
o
o
For our purposes in this class, think of CO2 & H + as the main members of the “ACID GANG” and HCO3 as the
“ALKALI GUY.”
--Too much CO2 or H+ in the blood = too much acid gang = acidosis. Too little CO2 or H += alkalosis.
--Too much HCO3 in the blood – too much alkali guy = alkalosis. Too little HCO3= acidosis.
Also, think of the lungs controlling or “ruling” CO2; they have little control of HCO3. Think of the kidneys as
controlling or “ruling” HCO3 & H+. (These principles are somewhat simplistic, but they are a good start for
E.
Acid / base sequelae of solute imbalance, ie, acid / base imbalance
1.
acidosis
a.
overview
1)
most often clinically measured as part of ABGs—arterial blood
gases; acidosis exists when the blood pH is < 7.35.
2)
as noted before, body needs narrow range of slightly alkaline
to counteract an overall tendency of metabolic activities
***Do memorize
towards
and remember,
acidosis, which is a state not well tolerated by the
“now
and forever,”
body.
all ABG values. This
includes: pH: 7.357.45
3)
4)
respiratory
b.
acidosis can cause variety of S&S, including:
a)
headache, disorientation
b)
nausea, vomiting
(Don’t
memorize–
c)
muscle pain, cramps.
is just listed for
d)
shortness of breath
perspective
e)
low blood pressure (BP), shock
on how
f)
organ failure, death.
damaging
types of acidosis are based generally on what caused the
acidosis: the
two types are metabolic and
26
metabolic acidosis (think of the word metabolic in the ABGs context
as
the
lungs
meaning that the acid/ base imbalance is related to a problem in
kidneys and/or any other disorder/body system EXCEPT the
(respiratory system).
Heavy acid gang (say,
too much H+)
overwhelms alkali guy
—this makes HCO3
“light”—ie, have a LOW
number. When the
acid gang takes over
like this, the pH
becomes low.
1)
2)
3)
exercising tooalkali guy is
in reliance onlight
because
needs.
the acid
gang has
“chased
him out of
acid gang
is heavy,
normal
making
are converted
pH low
acid (lactic
bala acid is full
nce
converted
needs—but
or systemically,
tissues and /or organ
4)
are
caused by a metabolic problem that results in one or more of
the following:
a)
excess accumulation of H+ (and other acids) in the body
b)
not enough excretion of H+ in the urine.
c)
not enough HCO3 being made.
d)
too much HCO3 being excreted in the urine.
any of the above can create a state of _LOW pH and low HCO3
an example of a metabolic acidosis etiology
a)
available O2 in a muscle is used up from
hard: hypoxia in those tissues results
anaerobic glycolysis for energy
b)
as a result, the pyruvate (AKA pyruvic acid) molecules
that are created during glycolysis do not undergo
processing via the Kreb’s cycle and instead
to another type of acid called lactic
of H+ ions)
c)
lactic acid can be a friend for awhile—it can be
to glucose in the liver for emergency energy
if acid levels get too high either locally
they become
“irritating” to the
systems.
other examples of processes that may result in metabolic
acidosis:
a)
kidney failure: because sick kidneys can’t excrete H+ or
make HCO3 acid accumulation acidosis.
b)
diabetic ketoacidosis: ketones have accumulated
because body is in sustained gluconeogenesis_
c)
poisons, drug overdose, alcohol: breakdown products
acidotic
Compensation (“fixing”):
--The lungs or the kidneys are the means of compensation to restore normal acid/base balance.
--If the original problem is metabolic, the lungs will “fix” (by controlling CO2 as a gas). Think like this: If the
kidneys are “sick” (as manifested by metabolic acidosis or alkalosis), they can’t do the fixing—the lungs must do the
fixing.
--If the original problem is respiratory, the kidneys will fix in various ways. Think like this: If the lungs are “sick”
(as
manifested by respiratory acidosis or alkalosis), they can’t do the fixing—the kidneys must do the fixing.
--To figure out HOW they will fix the problem, ask yourself, “what needs to happen to get back to normal pH?”
--Also, BE CAREFUL to clearly separate PROBLEM from COMPENSATION. When given a scenario, for example, FIRST
figure out what the PROBLEM is—metabolic vs respiratory acidosis or alkalosis. THEN figure out the COMPENSATORY
response.
********************
27
c.
respiratory
acid)acidosis
5)
compensation for metabolic acidosis (the body’s attempt to
return
to normal acid/base balance):
a)
the primary means of compensating for metabolic
acidosis is via the lungs.
b)
the lungs try to decrease the acid gang in the body by
increasing the amount of CO2 that is exhaled
c)
they do this by increasing the rate & / or depth of
respirations.
d)
end result is that the pH is increased back to normal.
respiratory acidosis
1)
state of low pH caused by a ventilation problem such as
diminished effectiveness of breathing or decreased
rate (more on this in pulmonary lecture).
2)
this results in retention of CO2 (accumulation of an
3)
compensation is by the kidneys: HCO3 production by the
kidneys will be increased to buffer the situation, ie, to
counteract the acid (CO2) that has accumulated from poor
ventilation.
Please note that there is a difference between talking about CO2 (an acid in the body) and PCO2 (partial pressure of CO2 as a gas).
But, FOR THIS SET OF READINGS AND THIS TEST, DON’T WORRY ABOUT PCO2 IN THE ABGS FOR NOW. We will come back to it in the
pulmonary section. But DO think of CO2 (without the “P” in front) as an acid. Anytime it accumulates, it will cause acidosis. If it
accumulates as a result of a metabolic problem, it will drive down the pH and the HCO3. If it accumulates as a result of a respiratory
problem, it will still drive down the pH but not affect the HCO3).
2.
alkalosis:
a.
overview
1)
clinically considered alkalosis when blood pH is > 7.45
heavy alkali
2)
alkalosis is a much less common abnormality than acidosis,
guy outweighs
light acid
though both can be very serious.
gang, making
3)
types of alkalosis: metabolic and respiratory, depending on
the pH high
cause
b)
metabolic alkalosis
1)
etiology-- a metabolic problem that results in one or more of
acid gang
the following:
light, pH
a)
excess accumulation of HCO3 in the body
high
b)
not enough excretion of HCO3 in the urine.
c)
too much acid (H+ and others) being excreted in the
alkali
urine or lost in other metabolic ways.
guy
heavy
d)
not enough acid being made
2)
any of the above can create a state of high pH and high HCO3
3)
some causes of metabolic alkalosis:
a)
large amount of vomiting.
b)
over-ingestion of bicarbonate (HCO3).
4)
compensation is via lungs, by decreasing rate & depth of
respirations.
c.
respiratory alkalosis
1)
of
CO2 in the
this in
2)
3)
3.
in
For test 1,
concentrate
mostly on
metabolic ABGs
alterations as
reflected in pH &
HCO3; there
might
be an
renal
answer choice for
respiratory
acidosis
in or
alkalosis, but look
> 7.45.
at the HCO3 and
if itproblem
has changed
out of the norm,
you know the
imbalance is
metabolic. In test
go up to
3 material, we will
encompass all
this info, adding
28
state of high pH caused by hyperventilation—increased rate
breathing results in “blowing off” more CO2— less
blood = LESS ACID GANG = higher pH. (more on
pulmonary lecture).
example of a cause of respiratory alkalosis: _anxiety (when
someone is anxious, they begin to hyperventilate)_.
compensation is via kidneys, by _decreasing amount of
HCO3
made or increasing its excretion.
summary of acid /base imbalances:
a.
respiratory acidosis: the cause is some sort of respiratory problem
which not enough CO2 is exhaled  CO2 is retained & causes
the pH to drop to < 7.35.
b.
metabolic acidosis: the cause is some sort of metabolic problem
usually related to anaerobic metabolism and /or the kidneys not
being
able to get rid of H+ or to make HCO3 (such as in
failure)—this causes the pH to drop to < 7.35.
c.
respiratory alkalosis: the cause is some sort of respiratory problem
which too much CO2 is exhaled and causes the pH to go up to
d.
metabolic alkalosis: the cause is some sort of metabolic
usually related to too much HCO3 ingestion, sick kidneys not getting
rid of HCO3, or vomiting too much acid—this cause the pH to
> 7.45.
e.
re: compensating for an acid/base imbalance: the kidneys
compensate for an imbalance caused by a respiratory
problem; the
lungs compensate for an imbalance caused
by a metabolic problem
(remember, “metabolic” includes
kidneys).