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Nursing 3366 Pathologic Processes: Implications for Nursing (ONLINE COURSE)

REQUIRED READING DOCUMENT #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:

Outline for Lecture: a. Information in a sidebar box is added knowledge for you, or a review of
previous info or sometimes some A&P info, etc
I. Overview b. If the info in the box is prefaced by “FYI,” you won’t be responsible
A. Physiology for it on a test.
B. Pathophysiology c. If there is no “FYI” preface, the information IS eligible for test
material. DO NOT FORGET TO STUDY THESE SIDEBAR NOTES!
C. Examples
II. Some basic physiologic concepts. Some standard language usage
A. Homeostasis clarifications:
B. Compensation and decompensation o “AKA” means “also known as.”
o “IE” or “ie” means “in other
III. Pathophysiologic concepts & terminology words.”
A. Disease vs disorder vs syndrome o “eg” means “for example.”
B. Terms relating to elements leading up to a disease o this sign before a word means
C. Terms relating to causes of a disease “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
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II. Some basic physiologic concepts.

A. 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” daily-life
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.
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III. 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 to
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
(***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. 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), malaise (“I
feel dragged out” or “awful all over”), systemic
lymphadenopathy
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d. 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 insidious and
last longer and/or wax and wane over months or years.
a) remissions—periods when S&S disappear or diminish
significantly (wane)
b) 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.”
e. terms relating to location of manifestations:
1) central
a) usually refers to problem, situation, etc, that is occurring
towards the center, or “core,” of the body
b) often used when referring to essential organ systems
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.
c) 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
Basic definition of i. ex—if we lose a lot of blood, the blood vessels of
“shock:” the periphery often constrict so that not a lot of
low BP plus S&S blood can circulate into those areas (mainly arms
of not getting
& legs)
enough blood to
different parts of ii. thus there is more blood going to central areas
the body (ex— such as the heart, brain, lungs, and kidneys—
confusion from blood has been shunted to those areas
not getting blood iii. this is why sometimes a sign of shock is cool, pale
to brain).
extremities.
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b)the more peripheral an area or problem is, or further
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.”
2. 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 & the
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.”
D. _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
sequela of getting pneumonia was that the patient stopped smoking;” but
most of time “sequela” is used with a negative connotation.
3. severity of sequela varies; examples of sequelae with various degrees of
seriousness:
a. sequela of rheumatic fever can sometimes be a bad heart valve.
b. possible sequela of chicken pox scarring
c. possible sequela of stroke weakness on one side of the body
**************************************************************

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.

 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.
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 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)

************************************
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: 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-Manual” if
 remission
 homeostasis you would like to know how to do a
 exacerbation
 compensation “flashcard concept map.” The emphasis in
 central
 decompensation
 peripheral doing flashcards this new way is to realize
 etiology
 proximal that knowing a word and its definition (rote
 risk factors
 distal memorization) is not enough—you must
 prognosis
 etiology understand its CONTEXT. That’s what gives
 comorbidity
 precipitating factor
 sequela it true meaning & application potential.
 idiopathic
 acute / acuity
 iatrogenic
 chronic
 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

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 multi-
purpose 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.
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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).
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Outline for Reading & Studying Genetic Influence in Disease:

A. Overview
1. definition of genetic disorders
2. categorizing genetic disorders
3. mitochondrial DNA disorders
4. multifactorial
5. chromosomal
6. single-gene
B. Single-gene disorders
1. overview/ categories: autosomal recessive, autosomal dominant, sex-linked
2. autosomal recessive
a. overview
b. example of autosomal recessive disorder--sickle cell anemia
3. autosomal dominant
a. overview
b. example of autosomal dominant disorder—polycystic kidney disease
4. sex-linked—example is hemophilia
C. 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 explanations
of terms:
1) example of inherited disorders—sickle cell disease is caused by an
“Environmental” inherited, altered (AKA, “mutated”) gene (see below)
is used here to 2) example of spontaneous—high level of exposure to radiation causes a
mean any
influence other
mutation in a gene becomes an “oncogene” which causes rapid, wild
than inherited. proliferation of cell growth skin cancer develops.
“Onco” prefix b. other ways to categorize include using the following four groupings: disorders
means “cancer-
related”
of mitochondrial DNA, multifactorial, chromosomal, single-gene.

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 here

4. multifactorial genetic disorders -- combination of environmental triggers and

variations / mutations of genes, plus sometimes inherited tendencies; examples:
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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:
a) fetal alcohol syndrome (FAS) occurs because toxicity of alcohol
causes gene mutations during gestational development.
b) “thalidomide babies” – born with abnormal arms and legs due
to mothers taking the drug thalidomide for nausea during early
pregnancy.

5. chromosomal disorders (AKA, chromosomal aberrations)

a.
FYI: chromosomal
disorders occur in ~1% of
live births (2% for women
older than 35 years) & are
leading known cause of
mental retardation & b.
miscarriage--about 50% of
all recovered first-semester
spontaneous abortions
(miscarriages) have major
chromosome abnormalities
that would have made
them not viable.
Putting things together: One of the
subcategories of chromosomal
disorders is aneuploidy. Trisomy 21
(Down’s) is a polysomic aneuploidy.
Did you understand that?
c.
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’ functionality is disrupted and they
don’t code proteins correctly, giving rise to the phenotype (S&S) of the
disorder.
alteration to NUMBERS of chromosomes is called an aneuploidy.
1) aneuploidies have the suffix “somy;” for instance, a generic term for
“more than usual numbers of chromosomes” would be polysomy--
Down’s syndrome is an example of a polysomy
2) Down’s is a disorder of abnormal numbers of chromosomes 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.
a) thus the other name for this type of Down’s is trisomy 21.
b) phenotype of trisomy 21 includes mental retardation and typical
physical characteristics such as low-set ears, epicanthic fold to
the eyes, short limbs, and a larger-than-normal tongue.
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.
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6. single-gene disorders – discussed below….

B. 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. single-gene disorders are inherited in recognizable patterns: autosomal
recessive, autosomal dominant, and sex-linked.
2. autosomal recessive disorder
a. overview
1) an autosomal recessive disorder occurs when a mutated (“diseased”),
FYI: other examples: recessive (“weak”) gene partners up with an allele that is also
phenylketonuria (PKU), recessive & diseased; those alleles are notated with two lower-case
cystic fibrosis, Tay-Sachs
disease, Wilson’s disease,
letters.
and many more. 2) the protein that they code for will then malfunction & an 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 of
KEY to drawings: alleles has the job of coding for the creation of normally shaped
= mutated gene
hemoglobin (Hgb)
= normal gene b) but if during fertilization a person inherits a sickle-cell disease
gene from mom – ie, a recessive, mutated Hgb-coding gene –
and ALSO inherits a sickle-cell disease gene from dad:
(1) this person would have a homozygous genotype of the
s s 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) those abnormal recessive alleles will code for abnormally-

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.”
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)
(3) 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.

2) phenotype—a person who has an ss genotype will HAVE the disease

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.
(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)
3. autosomal dominant disorders
a. overview
1)
2)
b. example of autosomal dominant disorder—polycystic kidney disease
(PKD)
FYI: other examples:
Huntington’s disease
1)
neurofibromatosis,
Marfan’s syndrome
When assigning notations
for autosomal dominant
diseases, the “big” letter will
be the dominant, diseased
allele, and the “little” letter
will be the normal, non-
diseased allele.
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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
(2) 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 disease gene
from one parent but a normal Hgb-coding gene from the other
parent, the person’s genotype for Hgb would be: _Ss_
b) we call this a “heterozygous genotype for sickle cell anemia” &
we know that because the NORMAL gene is dominant over the
sickle-cell recessive gene, the person will NOT have the disease
but they may pass on the gene to offspring.
(1) this is called being a carrier; so Ss is a sickle cell carrier.
(2) rarely, a carrier will have a milder phenotype of the
disease—ie, mild S&S; this situation is called “having the
trait.” (Someone with sickle cell trait has the genotype
Ss but has mild S&S of sickle cell disease.)
c) 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.”
occurs when a person inherits a mutated, diseased gene that is
dominant
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)
genotype & patho development
a) at a certain locus on a certain pair of chromosomes, a pair of
alleles has the job of coding for the creation of normal kidney
tissue
b) if during fertilization a person inherits a kidney tissue gene
that has a mutation, that gene will “want” to code for abnormal
kidneys.
c) in a dominant disease such as PKD, the mutated gene is the
strong one, so even if it is paired with a normal allele, it will
override the normal allele’s coding.

see if you can draw & label all 3 possible
allele pairing combinations for this
autosomal dominant 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?
4. sex-linked disorders
a.
When assigning
notations for X-
linked recessive
diseases, use XX
for women & XY
for men. Then
attach letters to
the X’s.
The “big” letter
will be dominant,
normal, non-
diseased allele, b.
and the “little”
letter will be the
diseased allele.
c.
FYI: Other examples
include certain types of
muscular dystrophy.
d.
12
d) in PKD, this results in the kidney tissue developing cysts,
which can reduces various kidney functions and lead to kidney
failure as a person goes through life.
2) genotype notation
a) if we use the letter “P” to designate PKD, the genotype for
someone that HAS the disease would look like this: PP or Pp.
b) only a person with a genotype of pp
(homozygous recessive) would NOT have the disease
or or
3)
S&S
a) hematuria (blood in urine), proteinuria, frequent kidney infections
b) pain at costovertebral angles and abdomen
c) kidney stones
normal physiology of sex chromosomes:
1) The two X’s in a woman work just like autosomal chromosomes – a
gene on one X has a partner allele at the same locus on the other X
that usually code for the same trait.
2) But in a male the genes on his X have no comparable partner allele on
his Y.
3) We notate these as such: Xl Xl (homozygous female); XL Xl
(heterozygous female); Xl Y or XL Y for the male.
types of sex-linked disorders:
1) possibilities include X-linked dominant, X-linked recessive, & Y-linked.
2) X-linked dominant and any kind of Y-linked diseases are rare—sex-
linked 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.”
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 chromosome, because
he only has a Y chromosome
3) therefore, the phenotype of most X-linked disorders is usually
expressed in male offspring.
example of sex-linked disorder—hemophilia
1) there are several types of hemophilia, each caused by different
gene mutations on the X chromosome.
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.
 13
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

I. Overview IMPORTANT NOTE: As you come across various numbers in your
A. Alterations in cellular-level function reading, be aware that very few of them will need to be memorized.
Exceptions include numbers that I feel will be very useful to know in your
B. Etiology of these disruptions nursing practice. Those numbers I will indicate with wordage such as
II. Hypoxia’s effect on cellular-level function “know now and forever.” That means they may come up again at any
A. Overview of hypoxia time in the semester and you will STILL need to know them. Please feel
free to ask me about this issue and any other.
B. Sequelae of hypoxia
III. Effect of nutritional alterations on cellular-level function.
A. Overview
B. A review of NORMAL glucose use and back-up systems
 14
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
A. A&P overview of select solutes This is A&P review info & won’t be tested as
such. However, understanding it is CRUCIAL
B. A&P overview of normal electrical function of cells to understanding the patho.
C. A&P overview of body fluid compartments
D. Cellular electrical problems secondary to alterations in electrolyte balance
E. Acid / base sequelae of solute imbalance, ie, acid / base imbalance
~~~~~~~~~~~~

Again, please review and understand the concept map

I. Overview “THE METABOLIC PATHWAY & DISTURBANCES.”

A. 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. Overview of hypoxia: has a spectrum of etiology and seriousness: from simply

overworked muscles in extreme exercise (the muscles use up 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
 15
Aerobic–
O2 is present b. this is because glycolysis is the only step that can operate under
(this is the ideal, normal, aerobic conditions, AND can also operate under anaerobic
“normal” conditions
situation).
Anaerobic– low 2. positive side to anaerobic glycolysis:
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 re-
acidosis—a state of
established.
greater-than-usual 3. negative side to anaerobic glycolysis:
concentration of
acidic substances
a. 2 molecule of ATP is not enough to keep going for a long time.
in the blood and b. also, every time the metabolic process must “recycle” through
cells.
glycolysis, multiple molecules of pyruvate (pyruvic acid) accumulate,
resulting in acidosis.

4. summary: two main sequela result from hypoxia:

Key physiologic principle: The
byproducts of the body’s
normal metabolic activities are
slightly more acidic than
alkaline. To counteract that
acidic tendency, the body
“likes” to keep a very narrow
and slightly alkaline pH range of
the blood—
7.35 to 7.45 (Know this
range “now & forever.”)
a. deficiency of ATP for cellular functions; ex—without ATP, the
Na / K pump of each cell cannot maintain normal electrical cell
membrane status and propagation of electrical impulses will be
disrupted.
b. 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

5. 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:

Glycogen is a large 1. if you have just eaten, glucose in the blood normally goes up, a state of
molecule that is too temporary hyperglycemia; this triggers the pancreas to secrete insulin
big to be used for
energy as it is, but to circulate to cells and assist in getting glucose molecules from the blood
when necessary it can into the cells to use as the main source of cellular energy.
be stimulated to break
down into small 2. if intake of food / glucose is greater than immediate cellular energy needs,
glucose molecules insulin directs the excess glucose to be stored as glycogen_ in the liver. This
that can be used
more effectively. is called _glycogenesis (genesis = “creation of”).
Think of it as “stored
glucose.” The processes above are considered to be “regulatory:” insulin triggers regulatory,
“building up” processes of 1) glucose entering cells, & 2) the creation of glycogen (glycogenesis).
 16
3. later, if you don’t eat and / or the availability of glucose is less than cellular
energy needs, a state of _hypoglycemia (low blood sugar)usually exists.
a. certain hormones called the counterregulatory hormones are triggered
by low blood glucose: AKA, stress hormones
1) epinephrine from the adrenal medulla because hypoglycemia is
2) cortisol from the adrenal cortex stressful for the body, so
they come “to the rescue.”.
3) growth hormone (GH) from the pituitary
4) glucagon from the pancreas.
b.
roles of these hormones include:
1) “alarms”—sensations of hunger, shakiness, sweating, irritability
BACK UP PLAN #1: —these are telling you to “EAT!”
2) if you don’t eat, the body takes the first step in its “back-up
Glycogenolysis plan:” the counterregulatory hormones stimulate 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”

BACK UP PLAN 1) if glucose is either unavailable or cannot get into the cell to participate
#2: in the metabolic pathway, and glycogenolysis has already exhausted a
person’s store of glycogen, the body breaks down fats and protein.
Gluconeogenesis 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
FYI: 3 main ketones: a) “good” characteristic of ketones: they can offer the body some
a) acetoacetic acid energy—usually enough to be a “stop gap” till glucose is
b) beta-hydroxybutyric acid available.
c) acetone (another acid) b) two “bad” characteristics of ketones:
(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.
***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.
 17
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. hyperketonemia is manifested by:

FYI: Of course, a diabetic 1)
would also have high serum 2)
glucose (no insulin = no
ability to move glucose from
bloodstream into cells =
hyperglycemia) and
glucosuria (glucose spilling
into urine), but right now we
are just discussing
hyperketonemia —the
“downside” of sustained
gluconeogenesis.
blood test showing high serum ketones.
AND usually the following as well:
a) blood test showing LOW (<7.35) blood pH—this would be called
ketoacidosis—a form of acidosis;
and/or
b) urine test which shows ketonuria (ketones spill into urine);
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.
FYI—dietary iron can be
obtained in liver, salmon,
beans, eggs; thiamine is in
lean meats, fish, milk. Also
many of our grocery
products are fortified with
these & other vitamins &
minerals.
b.
overview
1) glucose begins the metabolic pathway, but certain other molecules
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
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:
 18
CLARIFICATION: Beriberi is the a) because B1 is particularly important in the functioning of
disease name of general thiamine neurologic cells (including brain tissue), many S&S of depletion
deficiency. Wernicke-Korsakoff
syndrome is a group of of this vitamin (& other B vitamins) show up as neurologic
neurologic S&S especially seen in problems
alcoholics with beriberi.
b) examples of neurologic issues associated with thiamine
deficiency:
(1) Wernicke-Korsakoff syndrome – classically associated
paresthesia--“pins & needles” with alcoholism and manifested as memory loss and
feeling (like when your foot ataxia (staggering, uncoordinated gait)
falls asleep & “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
FYI—when I make long lists
a. cyanide present in insecticides, rodenticides, metal polishes, burning wool &
like this, it is not always
important to memorize the
silk, certain drugs such as nitroprusside; now considered potential
items specifically… most of
them time it is a certain
bioterrorism drug.
concept that I want you to
“get”… if you have
b. S&S of toxicity include headache, agitation, confusion, vomiting, eventually
questions about what to
know for a test in a “listing”
respiratory problems & death.
case like this, just ask.
c. mechanism of action-- inhibits cytochrome oxidase (look on 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.***

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 is to
balance Na+
1) the kidneys use Na & K to offset each other in the process of maintaining homeostasis
a) ex--if there is not enough Na and / or water in the body, aldosterone is secreted
by the adrenal gland--this stimulates the kidneys to “hold on” to Na and excrete K
b) the opposite happens if we need to “hold on” to K or if we need to get rid of Na.
2) also, the Na / K pump keep Na & K in the ratios needed to drive appropriate cell
membrane electrical impulse propagation
 19
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

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 Normal balance of tissue cell cations & anions …note
tissues. K+, Na+ are cations (I K+ K+ K+ Na+ Na+ that there are normally more anions than cations inside

------
randomly put 5 of them inside the the cell, giving the RMP its normal negative charge.
cell). The anions inside the cell are
represented by DASHES and there
are six of them. -90mv (normal RMP…the
resting state of the cell)

5) When an electrical signal reaches the resting cell, it + 30 mV (normal depolarization

changes the balance of cations & anions in the cell—
point—the contraction point-- the cell
more cations flood the cell. This increases the positivity of
the cell membrane until it reaches ~ +30 mV. This is the can now contract-- “go to work”)
“goal charge” for cell membranes to achieve in order to Normal “POLAR GAP
depolarize (contract). STATUS”..
K+ K+ K+ Na+ Na+ 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
This lightning bolt represents an -90mv this charge of +30 so
electrical signal coming from a that the cell can
nerve or previous cell that
(normal RMP) depolarize (contract)—
Cations like Na+ flood “go to work”. When
increases flow of cations into into cell & begin there is a normal RMP of
“our” representative cell, thus changing 90mV to a around -90mV, there is
changing the membrane charge more positive charge; a “normal” distance to
from -90mV to +30mV. ie, -90 starts becoming +30mV – ie, a “normal”
polar gap.
more positive
 20
C. A&P of body fluid compartments [NOTE: basically “fluid” translates to “water”]
1. 2 basic fluid compartments—extracellular & intracellular
a. intracellular fluid compartment is the fluid-filled space inside cells (solutes are dissolved in the fluid)
b. 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. Cellular electrical problems secondary to alterations in electrolyte balance

1. overview
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
Remember that solute compartment, a domino effect begins—diffusion of the solute particles
molecules results in changes in the next compartment, then the next, etc. (This
usually follow the
property of diffusion— occurs because the body is always striving to return to a normal, even,
they want to go to a homeostatic composition of solutes in each compartment.)
compartment where
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) the changes / imbalances exist until the body can “right” itself or in
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 by
the change occurring 2) then the K+ enters into the blood stream and increases the K+ level
FIRST in the blood there—in a sense, this creates an electrolyte imbalance, since now
compartment…
there is more K+ in one compartment (the blood) than usual.
 21
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

a. 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
SEE tissue cells will be affected
PODCAST –
it will help
you visualize 1) this causes a resetting of the cells’ resting membrane potential (RMP)
to a more positive number or a less positive number

2) if the RMP is reset to a MORE positive 3) if the RMP is reset to a LESS positive number
number than normal, it will shorten the than normal, it will lengthen the polar
polar status —this is called hypopolarization status—this is called hyperpolarization

3. 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, increased
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
 22
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: 2) hypocalcemia is a little harder to understand:

hypocalcemia has the
peculiar property of
causing more Na+ to
go INTO cells, so that
cells have abnormally
MORE cations inside
them hypopolarized.
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)
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.

3) if the spasms are severe and/or unrelenting, this is called tetany.

**** 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)
 23
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.

**** 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?
2. More cations have moved into cell = RMP is more positive than usual= shorter distance to +30 = hypopolarized
= more sensitive to stimulation = “hyperactive” S&S (muscle spasms, positive Chvostek’s sign, possible tetany, etc)
OR….
3. More cations have moved OUT of cell= RMP is less positive than usual= longer distance to +30 = hyperpolarized =
less sensitive to stimulation = “hypoactive” S&S (fatigue, lethargy, mental slowness).

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

IMPORTANT INFO ABOUT ABGS:

o “ABGs” stands for arterial blood gases—a measurement of oxygenation & acid/base balance in the blood.
o 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 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.
o 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 learning how to interpret ABGS.)
 24
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
***Do memorize and to counteract an overall tendency of metabolic activities towards
remember, “now and acidosis, which is a state not well tolerated by the body.
forever,” all ABG 3) acidosis can cause variety of S&S, including:
values. This includes:
a) headache, disorientation
pH: 7.35-7.45
HCO3: 22-26 b) nausea, vomiting (Don’t memorize–
pCO2: 35-45 c) muscle pain, cramps. is just listed for
pO2: 80-100 d) shortness of breath perspective
SaO2: 97% - 100% on how damaging
e) low blood pressure (BP), shock
acidosis can be.)
f) organ failure, death.
4) types of acidosis are based generally on what caused the
acidosis: the two types are metabolic and respiratory
b. metabolic acidosis (think of the word metabolic in the ABGs context as
meaning that the acid/ base imbalance is related to a problem in the
kidneys and/or any other disorder/body system EXCEPT the lungs
(respiratory system).
Heavy acid gang (say, too
1) caused by a metabolic problem that results in one or more of
much H+) overwhelms the following:
alkali guy—this makes a) excess accumulation of H+ (and other acids) in the body
HCO3 “light”—ie, have a
LOW number. When the
b) not enough excretion of H+ in the urine.
acid gang takes over like c) not enough HCO3 being made.
this, the pH becomes low. d) too much HCO3 being excreted in the urine.
2) any of the above can create a state of _LOW pH and low HCO3
3) an example of a metabolic acidosis etiology
a) available O2 in a muscle is used up from exercising too
alkali guy is hard: hypoxia in those tissues results in reliance on
light because anaerobic glycolysis for energy needs.
the acid
gang has b) as a result, the pyruvate (AKA pyruvic acid) molecules
acid gang is
“chased him that are created during glycolysis do not undergo normal
out of town”
heavy, processing via the Kreb’s cycle and instead are converted
making pH
low to another type of acid called lactic acid (lactic acid is full
balance
of H+ ions)
c) lactic acid can be a friend for awhile—it can be converted
to glucose in the liver for emergency energy needs—but
if acid levels get too high either locally or systemically,
they become “irritating” to the tissues and /or organ
systems.
4) 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_
 25
c) poisons, drug overdose, alcohol: breakdown products are
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.

********************
NOTE: when we talk about compensation in this context, we are referring to the BODY’s attempt to return things to homeostasis.
In the medical setting, however, we provide more immediate and different means to correct the problems. Many of you who are in
the medical field already may trip yourself up on a test by thinking about how we can jump in and help the patient with a drug or
intervention. ALL questions will be based on how the BODY compensates on its own.

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.
c. respiratory acidosis
1) state of low pH caused by a ventilation problem such as
diminished effectiveness of breathing or decreased respiratory
rate (more on this in pulmonary lecture).
2) this results in retention of CO2 (accumulation of an acid)acidosis
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 guy
outweighs light 2) alkalosis is a much less common abnormality than acidosis,
acid gang, though both can be very serious.
making the pH 3) types of alkalosis: metabolic and respiratory, depending on
high
cause
b) metabolic alkalosis
1) etiology-- a metabolic problem that results in one or more of
acid gang
light, pH high
the following:
a) excess accumulation of HCO3 in the body
b) not enough excretion of HCO3 in the urine.
c) too much acid (H+ and others) being excreted in the
alkali guy
heavy urine or lost in other metabolic ways.
d) not enough acid being made

c.
3. summary of acid /base imbalances:
a.
For test 1,
concentrate mostly
on metabolic ABGs
alterations as b.
reflected in pH &
HCO3; there might
be an answer choice
for respiratory
acidosis or alkalosis,
but look at the c.
HCO3 and if it has
changed out of the
norm, you know the d.
imbalance is
metabolic. In test 3
material, we will
encompass all this
info, adding PO2 &
PCO2 then. e.
26
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.
respiratory alkalosis
1) state of high pH caused by hyperventilation—increased rate of
breathing results in “blowing off” more CO2— less CO2 in the
blood = LESS ACID GANG = higher pH. (more on this in
pulmonary lecture).
2) example of a cause of respiratory alkalosis: _anxiety (when someone
is anxious, they begin to hyperventilate)_.
3) compensation is via kidneys, by _decreasing amount of
HCO3 made or increasing its excretion.
respiratory acidosis: the cause is some sort of respiratory problem in
which not enough CO2 is exhaled  CO2 is retained & causes
the pH to drop to < 7.35.
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 renal
failure)—this causes the pH to drop to < 7.35.
respiratory alkalosis: the cause is some sort of respiratory problem in
which too much CO2 is exhaled and causes the pH to go up to > 7.45.
metabolic alkalosis: the cause is some sort of metabolic problem
usually related to too much HCO3 ingestion, sick kidneys not getting
rid of HCO3, or vomiting too much acid—this cause the pH to go up to
> 7.45.
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).