Pathophysiology Exam 1 Study Guide:
Chapter 1: Concepts of Health and Disease
KNOW THIS:
- **Pathophysiology: is the study of the body’s response to dysfunction or disease;
“physiology of altered health”
o Example: Pathophysiology is the mechanism of high blood pressure
Aspects of the Disease Process:
- *Etiology: is the causes of disease
- *Pathogenesis: explains how the disease process evolves – it is the sequence of events
that take place from time of contact with etiologic agent until the expression of the
disease
- *Morphologic changes: refers to both gross anatomic and microscopic changes that are
characteristic of disease
- Clinical Manifestations: can be obvious or silent - for example an illness can cause
fever that makes it evident a person is sick, or there may be no symptoms and disease is
not discovered until it is advanced (many cancers)
- Diagnosis: is the designation of the cause of the health problem
- Clinical Course: describes the evolution of a disease, it may be acute or chronic
Disease Diagnosis and Predictive Factors
KNOW THIS:
*Sensitivity: measures the proportion of positive test results out of all truly positive samples;
(called a True Positive Result). A test’s sensitivity provides you with the percentage chance it
will correctly identify a person who has the disease and test positive on the test
- Sensitivity evaluates how good a test is at detecting positive disease
- Example: a test with 90% sensitivity will correctly return a positive result for 90% of
people who have the disease but will return a negative (** false negative**) for 10% of
people who have the disease and should have tested positive
- Test with 90% sensitive, it will correctly return a positive result for 90% of people who
have the disease
- Will return a negative, or false negative, for 10% of the people
Specificity: measures the true negative rate; (a true Negative Result). A test’s specificity
provides you with the percentage chance it will correctly identify a person who does not have the
disease
- Specificity can be calculated only from among people who do not have the disease- Example: a test with 90% specificity will correctly return a negative result for 90% of
people who don’t have the disease but will return a 10% (**false positive**) result for
people who don’t have the disease and should have tested negative
- False positive results are unduly stressful, and False Negative tests can delay diagnosis
and jeopardize the outcome of treatment
KNOW THIS:
- *A test that has high sensitivity, will have lower specificity
o An example of where you want to know the sensitivity and specificity is a
pregnancy test
Epidemiology
Epidemiology: the study of factors affecting the health and illness of populations; study of
disease occurrence in human populations, looks for patterns and factors in particular disorder and
disease
- Study risk factors for multifactorial disease such as heart disease and cancer in
populations
- “Whether something happens” rather than how
- Epidemiologic studies serve as a basis for clinical decision making, allocation of
healthcare dollars, and development of public health policies
Sources of Information for Epidemiologists:
*KNOW THIS: Know the difference between morbidity and mortality
- Morbidity: describes the effects an illness has on a person’s life
o Concerned with incidence, persistence, and long-term consequences
o *Significant impact on a person’s life; long term consequences of disease
o Ex: Arthritis has a low death rate but has a significant impact on a person’s life
- Mortality: pertains to the causes of death in a given population
o Statics to calculate leading causes of deathThree Levels of Disease Prevention:
*KNOW THIS: Know the difference between the three
- Primary: removing risk factors so disease does not occur
o No disease present
o Ex: folic acid to prenatal/pregnant women, counseling people how to adopt
healthy lifestyle, immunizations
- Secondary: early detection and treatment when disease is still curable
o Asymptomatic
o Ex: Paper smear, history taking, PE, labs, colonoscopy
- Tertiary: preventing further deterioration or reducing complication of disease
o Clinical course/intervention
o Ex: antibiotic use, b-adrenergic drugs to decrease death in MI, provision for eye,
foot, and cardio exams in people with DM
Evidence-Based Practice: the conscientious, explicit, and judicious use of current best evidence
in making decisions about the care of individual patients
- MUST be based on current evidence
Cross sectional studies: can be used to compare the prevalence of a disease in those with a
specific factor with the prevalence of a disease in those who are unexposed
- Example: Heart disease in smokers vs. nonsmokers
Case control studies: comparing two groups – those with a disease or condition (cases) and a
very similar group of people who do not have the disease or condition (controls)
- Example is the characteristics of maternal alcohol consumption in infants born with FAS
(cases) can be compared with those in infants born without the syndrome (controls)
- Another example would be lifeguards who developed facial skin cancers (cases)
compared to lifeguards who did not develop facial skin cancers (control)
Cohort studies (also known as Longitudinal studies): are followed over a period of time to
observe specific outcome
- May be a single group or two groups specifically selected where one group has been
exposed and the other has not, or a single exposed group in which the results are
compared with the general populationChapter 2: Cell and Tissue Characteristics
*KNOW THIS:
Transcription: occurs in the cell nucleus and is the process in which RNA is synthesized from
the DNA template; occurs when the DNA is copied into a complementary strand of mRNA
- *Messenger RNA (mRNA): is formed from DNA in a process call **transcription
- mRNA travels to ribosomes in the cytoplasm so the instructions can be used to make
proteins
- **transcription
Translation: after the mRNA is processed (adding nucleic acids to the ends and splicing out the
exons), it is a mature molecule and is passed into the cytoplasm of the cell, where translation
occurs. Translation is the synthesis of a protein using the mRNA template
- *Transfer RNA (tRNA): transports amino acids to ribosomes so that mRNA can be
turned into a sequence of amino acids, this is known as **translation, and uses mRNA
template to link amino acids to synthesized proteins
- The new polypeptide chain must fold up into its unique three-dimensional conformation
- Molecular Chaperones: special classes of proteins that assist in the folding of many
proteins to make more efficient
o Disruption of these chaperoning mechanisms causes intracellular molecules to
become denatured and insoluble
o These denatured proteins tend to stick together, precipate and form inclusion
bodies which is a pathological process that occurs in Parkinsons, Alzheimers,
and Huntington Disease
Functional Components of the Cell
KNOW THIS
- Protoplasm: the colorless material compromising the living part of the cell, including the
cytoplasm, nucleus, and other organelle; intracellular fluid; water (70-85%), proteins,
lipids, carbohydrates, electrolytes
-
o *Electrolytes within protoplasm include:
Potassium, Magnesium, Phosphate, Sulfate, and Carbonate Ions
o Small quantities of sodium, chloride, and calcium are present and participate in
reactions necessary for the cells metabolism and they help generate signals in
neurons, muscle cells, and other cells- Cytoplasm: includes the fluid and organelles excluding the nucleus but within the cell
membrane surrounding the cell; excludes nucleus
o Cytoplasm is a solution that contains water, proteins, lipids/fats,
carbohydrates, electrolytes. Pigments may also accumulate in the cytoplasm
One example is melanin, which gives skin its color
o Some pigments are not normal parts of cells. For example, when the body breaks
down old red blood cells, pigments in red blood cells are changed to the pigment
bilirubin, which the body can excrete; some conditions cause bilirubin to build up
in cells to cause jaundice, which is seen clinically by a yellowish discoloration of
the skin and sclera
o Cytoplasm also contains ribosomes, endoplasic reticulum, the Golgi complex,
mitochondria and other particles such as lysosomes which break down excess cell
parts and kind of clean up the cell
o The pH of the cytoplasm is approximately 5:
**Lysosomes require an acidic environment
o Organelles present; similar to organs in body
Organelles include: Ribosoms, ER, Golgi Complex, Mitochondria,
Lysosomes and Proteasomes
- Cytoskeleton: within cytoplasm is a cytoskeleton, which controls cell shape and
movement (by microtubles), it includes flagella and cilia
KNOW THIS
o *Flagella: only has one flagellum (Flagella is a single flagellum)
o Eukaryotic Flagella cells are classified as only having one flagellum
o In humans, sperm cells are the only cell type with flagella
Gamete
o *Cilia: contain large numbers of flagellum
o *Cilia are found on epithelial linings, including the nasal sinuses and bronchi in
upper respiratory system
o They help by sweeping out bacteria and dust trapped in mucus up the
airways to the mouth so they can be swallowed (mucus escalator)
Damage to ciliated cells causes a cough which is then used to remove
these substances from airway
- The Nucleus: “genetic material home”
o Can be thought of as the control center for the cell because it contains the
instructions to make proteins and proteins can then make other molecules needed
for cellular function and survival
The Nucleus contains DNA which contains genes and genes contain
instructions for cellular function and survival
o *Eukaryotic cells have at least one nucleus Some cells contain more than one nucleus such as osteoclasts (bone cells)
usually contain 12 nuclei or more
o *Prokaryotic cells (such as bacteria) lack a nucleus or nuclear membrane
KNOW THIS
- *Ribosomes: are the site of protein synthesis
o There are 2 subunits of ribosomes that are made up of rRNA and proteins
o During protein synthesis, the two subunits are held together by a strand of mRNA
- Mitochondria are the power plants of the cell because they contain the enzymes that can
change carbon-containing nutrients into energy that is easily used by cells, this is also
known as cellular respiration because it requires oxygen
o Mitochondria contain their own DNA and ribosomes, and they are self-replicating
o The DNA is different than chromosomal DNA, it is known as mtDNA – it is a
double stranded molecule that contains the instructions to make 13 proteins
needed for mitochondrial function
o mtDNA is inherited from the mother and is used to study inheritance from
the mother’s lineage
o Most cells in the body can be affected by mtDNA mutations
o Mitochondria function as the key regulators of apoptosis, or programmed cell
death
o **Too much or too little apoptosis is implicated in a wide range of diseases, such
as cancers where there is too little apoptosis and neurodegenerative diseases
where there is too much apoptosis
- Cell membrane: separates intracellular from the extracellular environment
o It is semi-permeable structure that helps determine what can and cannot enter the
cell; water can cross
o It contains receptors to hormones, and neurotransmitters, and helps regulate cell
growth and division
Cell Membrane Components: membrane is made up of lipids, cholesterol and proteins
- Lipids: the basic fluid structure of the membrane and serves as a semipermeable barrier
o Phospholipids with a hydrophilic head and a hydrophobic tail
- Proteins: span the entire lipid bilayer
o Ion Channels
- GlycocalyL: participates in cell-to-cell recognition and adhesionKNOW THIS
- Membrane Potential: electrical potentials across membranes as a result of ion
distribution
- Ion Channels: rapid signaling between electrically excitable cells; opens or closes ion
channels
- The electrical charge on ions such as Na and K make it difficult to cross the lipid layer of
the cell membrane (rapid movement is needed for many functions such as nerve activity)
- Ion channels are highly selective, some only allow for the passage of sodium ions, and
others are selective for potassium ions, calcium ions or chloride ions
- Concentrations are different on either side of membrane; difference in charge on either
side of membrane
- Some channels are gated, others remain open and are called leak channels (the types of
leakage channels with greatest significance in neurons are potassium and chloride
channels)
- Channels that have to be crossed, they can be gated, can remain open, rapid
movements of particles take place
Three Types are:
1. **Voltage gated: open and close with changes in membrane potential
a. This refers to the concentrations of ions on either side of the membranes which
lead to differences in charge on the two sides of a membrane
b. These differences create electrical potentials across the cell membranes of most
cells of the body, and these electrical potentials are called membrane potential
2. Ligand-Gated channels or chemically Gated channels: which open or close when
chemicals bind to the channels
a. These channels are also receptors and the chemicals that bind to the receptors are
called ligands (acetylcholine which is a neurotransmitter)
3. Mechanically Gated: open or close in response to mechanical stimulations such as
vibration, tissue stretching, temperature or pressure
Cell Receptors and Ligands:
- Ion Channel-Linked Receptors
o Rapid synaptic signaling between electrically excitable cells
- G Protein-Linked Receptors: rely on intracellular regulatory proteins to convert
EXTERNAL signals to INTERNAL signals
o The ON-OFF switch for signal transduction
o G Protein-Linked Receptors bind to GDP and GTP
o Activated “on” state, G protein binds GTPo “Off” state, G protein binds GDP
o GTP is bound - ACTIVE
o GDP is bound – INACTIVE
- Enzyme-Linked Receptors
o Stimulate cellular response
- Intracellular Receptors
The Cell Cycle and Cell Division
- Aerobic: with O2; pathway occurs in mitochondria
- Anaerobic: without O2; glycolic pathway occurs in cytoplasm
*KNOW THIS: Types of Cell Division
Types of Cell Division:
- *Mitotic Cell Division: cell division stage; occurs in somatic cells
- *Meiosis: occurs in gamete-producing organs (reproductive organs)
o Sex organs – sperm and egg
Movement of Substances Across the Cell Membrane:
Cell membrane is responsible for differences in composition of intracellular and
extracellular fluids
- Extracellular: more Sodium, Calcium, Chloride ions
- Intracellular: more Potassium, less Sodium (active transport needed)
Movement occurs in 3 ways:
- Simple Diffusion: following concentration of gradient
- Carrier Proteins: active transport; responsible for transporting only one type of
molecule
- Channel Proteins: transfer water-soluble molecules and serve as ion selectivity filter
- Passive Transport: chemical or electrical gradients and do NOT require energy
o Difference in number of particles across membrane creates a gradient (chemical
or electrical)- Diffusion: substances become widely dispersed and reach uniform concentration because
energy from spontaneous kinetic movements (ions move from higher to lower
concentration); move freely to become equally distributed across membrane (sodium
ions can diffuse from outside of cell to inside where sodium is in lower
concentrations)
o Facilitated Diffusion: glucose cannot pass through the membrane and need
assistance from a transport protein – uses insulin (if not enough insulin;
hyperglycemia will result)
- Osmosis: osmotically active particles regulate flow of water; movement of WATER
molecules across a semipermeable membrane
o Passive diffusion/no energy
o Seen in kidneys and in dialysis
- Active Transport: selected molecules are transported across membrane using energy
driven (Na/K -ATPas e Pump)
o Na/K Pump: moves 3 Na ions from inside to OUTSIDE cell; moves 2 K ions
from outside to INSIDE cell
o Moves AGAINST concentration gradient
o This process uses ATP and is therefore AEROBIC
- Endocytosis: “opening”; process by which cells surround and take in minerals from their
surroundings (ex: LDL uses to be carried into liver); membrane forms a vesicle that
engulfs particle and transports into cytoplasm and across membrane where it is released
o Pinocytosis: “small particles”
o Phagocytosis: “large particles”; engulfment and then killing microorganisms and
particulate matter
- Exocytosis: allows intracellular substances into extracellular spaces
o Important in removing cellular debris and releasing substances
Organization of Cells into Tissue:
- Epithelial: body’s surface and lines internal closed cavities; avascular
o Receive O2 and nutrients from capillaries of connective tissue which epithelial
rests on
*KNOW THIS
- Epithelial tissue: covers the body’s surface and lines the internal closed cavities,
including blood vessels, and body tubes that connect with the exterior of the body
(gastrointestinal, respiratory, genitourinary tracts)
o Also forms secretory portion of glands and their ducts
o There is no vascular supply, epithelial tissue receives oxygen and nutrients
from the capillaries of the connective tissue on which it rests- **Epithelial tissue must be kept moist, this is done on the skin by a waterproof layer
called **keratinocytes
- **Keratinocytes: waterproof layer on skin that keeps epithelial tissue moist; this
prevents evaporation of moisture from deeper skin cells
*KNOW THIS
- **Connective Tissue: can become connective tissue proper which includes loose,
adipose, reticular or dense connective tissue
o Or specialized connective tissue that functions to support soft tissues of the body
and store fat (cartilage, bone and blood cells)
Extracellular Matrix
*KNOW THIS
**Collagen: is the most common protein in the body
**Elastin: acts as a rubber band, it returns to its original form after being stretchedChapter 3: Cellular Adaptation, Injury, and Death
Cells adapt to changes in the internal environment:
- Cells adapt to increased work demands by changing in:
o Size (atrophy and hypertrophy)
o Number (hyperplasia)
o Form (metaplasia)
**KNOW THIS:
- Hyperplasia: 2 common types of hyperplasia are hormonal and compensatory –
NUMBER OF CELLS
o Hormonal Hyperplasia: breast and uterine enlargement during pregnancy are
examples of hormonal hyperplasia that results from estrogen stimulation
o Compensatory hyperplasia: liver regeneration after removal
- Metaplasia: usually occurs as a response to chronic inflammation or irritation and allows
for substitution of cells that are better able to survive under the circumstances; it is
an abnormal change in the nature of tissue – as cells are damaged, a hardier version
replaces the normal strata of cells
o During metaplasia: one cell may be replaced only by another cell of the same type
o An epithelial cell must replace an epithelial cell, it cannot be converted to a
connective tissue cell
- **Chronic GERD is a risk factor of Barretts esophagitis and esophageal cancers
- Barretts Esophagitis is the presence of a metaplastic columnar-lined esophagus
induced by GERD, and patients with BE have a 30-40% chance of developing BE
adenocarcinoma
Sources of Intracellular Accumulation:
**KNOW THIS: know about bilirubin and possible causes
- Abnormal Endogenous Products: when there are substances produced faster than the
metabolism or removal
o This can be a result from genetic disorders that disrupt the metabolism of certain
substance
- Jaundice: A buildup of bilirubin causes Jaundice
o This is a yellow discoloration of tissue due to the retention of bilirubin caused by
increased bilirubin production from red blood cell destruction, obstruction ofbile passage into the intestine, or toxic diseases that affect the liver’s ability to
remove bilirubin from the blood
- Exogenous Products: ex: carbon in the form coal dust which blackens the lung tissue
and can cause serious lung disease
- Metastatic Calcification: occurs in normal tissue
- Dystrophic Calcification: occurs in dead of dying tissue – prolonged ischemia
Mechanisms of Cell Injury:
- Be familiar with Mechanical aka TRAUMA; Extreme of temp aka hypothermia;
Electrical aka when electricity penetrates the skin and passes rapidly; Ionizing radiationimmediately kills cells; Ultraviolet radiaotion aka “xeroderma pigmentosum” - sunlight
induced skin damage; Non-ionizing radiation aka microwave
*KNOW THIS
- Free Radicals: free radicals can disrupt and damage cells
o Ex: formation of free radicals in liver from Tylenol – causes liver damage
o Ionizing and UV radiation can cause Reactive Oxygen Species production
o Can cause oxidative stress which is a condition that occurs when the generation
ROS exceeds the body’s ability to neutralize and eliminate ROS
o Oxidative stress is thought to play a role in the development of cancer
- Antioxidants: inhibit reactions of ROS or prevent the uncontrolled formation of ROS
o Include: Vitamin A, E, C, Glutathione, Flavonoids, Selenium and Zinc
Hypoxic Cell Injury:
- Hypoxia: the ultimate cause of cell death
o Causes powerful failure in the cell
o In some cases, cellular changes are reversible if O2 is restored in a timely manner
The longer tissue is hypoxic, the greater chance of irreversible cellular
injury
Impaired Calcium Homeostasis:
*KNOW THIS
- Calcium functions as an important second messenger and cytosolic signal for many cell
responses- In general, intracellular calcium ion levels are kept extremely low compared with
extracellular levels
- The low intracellular calcium levels are maintained by membrane associated
calcium/magnesium-ATPase exchange systems
- **Ischemia and certain toxins lead to an increase in cytosolic calcium because of
increased influx over the cell membrane and the release of calcium from
intracellular stores
- The increased calcium can inappropriately activate a number of enzymes with
potentially damaging effects
“First, calcium can activate certain enzymes that you might not necessarily want to activate, like
proteases that can slice up proteins and damage the cell’s cytoskeleton, which remember is the
structural framework that keeps the cell together. Also, endonucleases can be activated, which
can cut up DNA, the cell’s genetic material. Enzyme activation isn’t the only effect calcium can
have; calcium can get into the mitochondria, causing a cascade the leads the mitochondrial
membrane to be more permeable to small molecules and so it lets a molecule that usually stays in
the mitochondrial, cytochrome c, to leak out into the cytosol.
This is a big big red flag to the cell that things have gone south, and is kind of analogous to the
self-destruct button, and activates a process called apoptosis, or programmed cell death. This is a
bit like cellular suicide. At this point, the cell’s not in good shape, right? And all this happens
eventually because of a lack of oxygen, or because of hypoxia”.
*KNOW THIS
- Membrane Damage: membrane damage can result from
o Inactivation of the Na+/K+ ATPase
o Oxidation of phospholipid
o Ischemic activation of Ca2+-regulated protease
Programmed Cell Death:
*KNOW THIS
- Apoptosis: an orderly process that maintains balance in the body (equated with suicide);
cells have a programmed date of expiration
o This process eliminates cells that are worn out, been produced in excess,
developed improperly, and/or have genetic damage
- When there are cells that are precancerous, infected with a virus, or a cell’s DNA is
damaged, the cell will typically try to repair itself, but if the cell is damaged beyond
repair it will send itself into **apoptosis so that it does not pass on the damaged DNA
- If cells have damaged DNA but fail to undergo Apoptosis – they can continue to divide
and pass on the damaged DNA and that person **may be on their way to developing a
cancer- Cancer is a scenario where too little apoptosis occurs and results in malignant cells
that won’t die
- Apoptosis is important in the *immune system
- Psoriasis is an example of a decrease in apoptosis of keratinocytes
- Necrosis: refers to cell death in an organ or tissue that is still part of a living person
o Often interferes with cell replacement and tissue regeneration
o Gangrene occurs when a considerable mass of tissue undergoes necrosis
Chapter 4: Genetic Control of Cell Function and Inheritance
Stable DNA molecule
- Contains the information needed for control of cell structure and function
- Every cell in the body contains the same genetic information.
o Each cell type uses only a portion depending on its structure and function
- Four bases making up the alphabet of the genetic code:
o Adenine
o Cytosine
o Guanine
o Thymine
- Transcription creates a complimentary mRNA copy
- The nitrogenous bases carry the genetic info and are divided into 2 groups:
o Pyrimidine bases: thymine (T) & cytosine (C)
o Purine bases: adenine (A) & guanine (G)
- Base pairing rules: A with T and G with C: operate to assemble a new DNA strand;
these 4 bases make up alphabet for genetic code
*KNOW THIS
- *Transcription occurs in the cell nucleus and is in process in which RNA is synthesized
from the DNA template
o Transcription creates a complimentary mRNA copy- **mRNA** Messenger RNA: is the template for protein synthesis
- Each human has 23 pairs of different chromosomes
o 1 pair derived from mother and 1 pair derived from father
- Autosomes:
o 22 pairs of chromosomes alike in males and females
- Sex Chromosomes:
o Make up the 23rd pair, determining the sex of a person
o XX: female or XY: male
DNA Mutations:
*KNOW THIS
- Germ Cell: a cell that contains half the number of chromosomes of a somatic cell and is
able to unite with one from the opposite sex to form a new individual
- in simple terms: an egg cell or sperm cell
- Germ cells pass on the genes
o ONLY GERM CELL LINE MUTATIONS CAN BE PASSED TO
OFFSPRING
o To be transmitted to offspring, the mutation must be in the GERM cell line
- Somatic Cell: Only DNA changes (mutations) that occur in germ cells can be inherited
in offspring
Protein Synthesis:
*KNOW THIS pg. 80
- RNA interference RNAi: stops genes from making unwanted diseased proteins
o This is a naturally occurring process in which small pieces of double stranded
RNA suppress/block gene expression
o Scientists are approaching the problem of faulty gene activity by using RNAi for
treatment of gene-linked disorders; gives them the ability to practice reverse
genomics
Harnessing RNAi for HIV and Hep C treatment
o In viral infections RNAi would serve to control infection by preventing the
synthesis of viral proteinsGene Expression:
- Gene Expression: the degree to which a gene or particular group of genes is active
- Posttranslational processing: involves the proper folding of the newly synthesized
polypeptide chain into its unique three-dimensional conformation
o Molecular chaperones
o Combination of peptide chains
o Cofactors
o Enzymatic modification
*KNOW THIS
- The folding of many proteins is made more efficiently by special classes of proteins
called Molecular Chaperones
o They assist in the transport to the site in the cell where the protein will carry out
its function and help prevent misfolding of existing proteins
- *Disruption of these chaperone mechanisms causes intracellular molecules to
become denatured and insoluble
- These denatured proteins tend to stick to one another, precipitate and form inclusion
bodies, which is the pathologic process that occurs in:
o Parkinsons, Alzheimers and Huntington diseases (pg 69)
Cell Division:
*KNOW THIS pg. 73
- In the body, we have 46 chromosomes; 23 pairs
- Mitosis: occurs in somatic cells
o *Involves the replication of DNA to duplicate somatic cells in the body
o Results in formation of 23 identical pairs of chromosomes
- Meiosis: limited to replicating germ cells
o Results in formation of gametes or reproductive cells
o Only found in testes or ovaries and produces ovum and sperm
o Each has a single set of 23 identical pairs of chromosomes
*KNOW THIS
- Karyotype: the number and appearance/photographic of the chromosomes in the cell
nuclei (chromosomal appearance)o The arrangement of a person’s chromosomes; prepared by special lab techniques
in which cells are cultured, fixed and stained to display patterns
o *Simply put: the number and visual appearance of the chromosomes in the
cell nuclei
o *After the metaphase is stripped the chromosome
Gregor Mendel studied inheritance by experimenting on pea plants
- Mendels First Law: (law of segregation) inherited alleles are separated when producing
gametes
o During maturation, the primordial germ cells of both parents undergo meiosis,
dividing the number of chromosomes in half
o The two alleles from a gene locus separate; each germ cell receives only one
allele from each pair
- Mendel Second Law: (law of indep assort) alleles get distributed to offspring randomly
o The alleles from the different gene loci segregate independently and recombine
randomly in the zygote
- Mendelian Patterns of Inheritance: Punnet Square
*KNOW THIS
- Genotype: genetic information stored in the sequence of base pairs
o Inherited by parents
o Cannot see this
- Phenotype: refers to recognizable traits, physical or biochemical, that are associated with
specific genotype
o Influenced by genotype
o *Physical manifestation of genetic information (blood type, eye color, not
suffering from a disease/suffering from a disease, etc)
o People with brown eyes may have same phenotype but different genotype
- *Key difference: a genotype is inherited from the parents, the phenotype is not
- Phenotype is influenced by Genotype but they are not the same
- Haplotype map: identifies the slight variations in the human genome that affect a
person’s susceptibility to disease and responses to environmental factors such as
microbes, toxins, and drugs
Arrangement of Alleles:- Homozygotes: person whom the two alleles of a given pair are the same at gene locus
o AA or aa
o Either dominant OR recessive
o Code exact same gene product
- Heterozygotes: person whom the two alleles of a given pair are different
o Aa
o Have dominant AND recessive
- Recessive Trait: one expressed only in homozygous pairing (aa)
- Dominant Trait: one expressed in either a homozygous or heterozygous pairing (AA or
Aa)
- Carrier: person who is heterozygous for a recessive trait and does not manifest the trait
- Polymorphism: more than one normal allele (alternate forms at same locus)
Chapter 5: Genetic and Congenital Disorders
Genetic Factors, Environmental Factors, Intrauterine Factors (rare)
- Genetic Disorders: can affect a single gene (mendelian inheritance) or several genes
(polygenic inheritance)
o Single gene mutations may be present on an autosome or on the X chromosome as
dominant or recessive
Disorders of Single-Gene Inheritance (Mendelian)
*KNOW THIS
- Autosomal Dominant Disorder: affected parent has 50% chance of transmitting
disorder to each offspring; the unaffected do not transmit the disorder
- Individual only needs to inherit the mutated allele from one parent in order to
manifest the disease
o Age of onset: later in life
o Portray variable expressivity
o Marfan Syndrome
- Autosomal Recessive Disorder: both parents may also be unaffected but are both
carriers of the defective gene; affect both sexes
o Age of onset: earlier in life
o Include almost all inborn errors of metabolismo PKU is a metabolic disorder
- X-Linked Recessive: sex-linked disorders; always associated with X chromosome;
inheritance pattern is predominantly recessive
- Typically transmitted by unaffected mother who carries one normal X chromosome and
one mutant X chromosome
- Females are rarely affected because they have 2 XX (heterozygotes/carriers) and have the
presence of one normal X which is dominant over mutant X, whereas all males who
receive the gene are typically affected as they only have the mutant copy
o Females have 50% chance of transmitting mutant gene to son (X or X)
o Females have 50% chances of transmitting mutant gene as CARRIER (X or X)
o Male passes 100% mutated X to his daughters making them all carriers; male
does not transmit any carriers to his sons because Y genes are unaffected
*KNOW THIS
- Autosomal Dominant Disorder
o *Marfan Syndrome: a connective tissue disorder manifested by changes in the
skeleton, eyes, and cardiovascular system – mitrol valve prolapse & aortic
aneurysm
- Autosomal Recessive Disorder
o *Phenylketonuria: caused by a buildup of phenylananine; there is a defect in the
gene that helps create the enzyme that breaks down phenylananine
Intellectual delays, brain damage, behavioral symptoms and seizures
May have a musty odor to breath, skin and urine and may have skin
rashes
o Main treatment: low protein diet, these patients must avoid meats, nuts and dairy
- X-Linked Disorders the disease will affect both males and females that inhe3rite a copy
- of mutated X chromosome
o Fragile X: can cause mild to severe intellectually
o Females tend to have milder symptoms
Characteristics of Multifactorial Inheritance Disorders
- **Caused by MULTIPLE GENES AND ENVIRONMENTAL FACTORS
- Single and multiple genes
- Aneuploidy: abnormal number of chromosomes; this happens when there is a failure of
chromosomes to separate during oogenesis or spermatogenesisTypes of Chromosomal Disorders:
*KNOW THIS
- Monosomy: only 1 member of a chromosome pair
o Defects are severe and can cause miscarriage in utero
- Polysomy: presence of more than two chromosomes to a set XXXY
- Down Syndrome (Trisomy 21): caused by error in cell division during meiosis;
“meiotic nondisjunction”
o Several prenatal screening tests including: a-fetoprotein, AFP, hCG, and
Ultrasound which may show nuchal translucency
o Definitive diagnosis of Down Syndrome in the fetus is through chromosomal
analysis using Chorionic Villus Sampling, Amniocentesis, or Percutaneous
Umbilical Blood Sampling
o Risk increases with maternal age
o Characteristics: epicanthal folds, slanted eyes, flat facial profile, congenital heart
disease, acute lymphoblastic leukemia, growth failure-mental retardation, flat
occiput, big protruding wrinkled tongue, intestinal malformations, short, broad
hands with simian crease, wide gap between 1st and 2nd toes
- Turner Syndrome (Monosomy X): often not diagnosed until adolescence
o Females have absence of all or part of the X chromosome or all or part of the
chromosome is abnormal, or display a mosaicism
o Most women with Turner are infertile due to failure of ovarian development – 2%
of women do get pregnant but pregnancy can be dangerous if there are heart
issues – and they will have a 30% chance of having a fetus with birth defect
o There is no association between Turner Syndrome and advanced maternal age
o Short in stature but body proportions are normal
* pg 91- Klinefelter Syndrome (Polysomy X):
o Male is born with one or more extra X chromosomes (47, XXY), often not
diagnosed until adulthood or in some with mild signs it may never be diagnosed
o These patients produce little to no sperm and are often diagnosed until they seek
evaluation for infertility*
o *page 92
- Mitochondrial DNA Disorders: mitochondria contain their own DNA which is distinct
from nuclear DNA
o All mtDNA disorders are inherited on MATERNAL line
o Subject to mutations at a higher rate than DNA
o No repair mechanisms
o Deafness is associate with mtDNA mutations
Disorders caused by Environmental Influences:
*KNOW THIS
- **Teratogenic agents: can produce abnormalities during embryonic or fetal
development
o Radiation, drugs, chemical substances and infectious agents
- Organogenesis: the period of rapid differentiation and development of organs; time in
which embryo is most easily disturbed (most susceptible to teratogenic agents)
o 15 – 60 days after conception
o **Week 4 exposure to teratogenic toxins cause Heart and CNS deformities in a
fetus
*KNOW THIS
Fetal Alcohol Syndrome:
- Prenatal or postnatal growth retardation (wt or length below 10th percentile)
- CNS involvement
o Neurologic abnormalities
o Developmental delays
o Behavioral dysfunction
o Intellectual impairment
o Skull and brain malformation
- A characteristic face:
o Short palpebral fissures
o Thin upper lip
o Elongated, flattened midface and philtrum
o More prominent as infant develops but becomes less prominent in adulthood
Categories for Determining Safety of Drugs During Pregnancy:- Starts at Category A (least teratogenic/dangerous), B, C, D, and X (contraindicated
because of proven teratogenicity – cocaine and alcohol)
Other Contraindications During Pregnancy:
- Vitamin A Derivatives
- Folic Acid Deficiency
o Linked to Neural Tube Defects (NTD)
Components of Genetic Assessment for Fetal Abnormalities:
- Lab test: chromosomal analysis and biochemical studies often precede a definitive
diagnosis
TORCH Syndrome: any group of infections in newborns due to one of the TORCH infectious
agents having crossed the placenta during pregnancy
- Toxoplasmosis
- Other agents (Syphilis, Varicella, EBV, Listerosis, Leptospirosis, TB, and HIV)
- Rubella (or German measels)
- Cytomegalovirus
- Herpes Simplex
Clincal Manifestations:
- Growth retardation
- Brain abnormalities (micro/hydrocephalus)
- Eye and ear
- Liver (jaundice)
- Hemopoietic system
- Lungs and Heart
Chapter 6: Neoplasia
*KNOW THIS
- **Neoplasm: disorder of altered cell differentiation and growth
o Neoplasms do not obey the laws of normal cell growth like hypertrophy and
hyperplasia do
- **Cancer is a disorder of altered cell differentiation and growth- Differentiation: process of specialization; new cells acquire the structure and function of
cells they replace
The Cell Cycle
*KNOW THIS
- **Know that genetic information is duplicated during the cell cycle
- Genetic information is DUPLICATED during cell cycle
- Check points in cell cycle provide opportunities for monitoring the accuracy of DNA
replication
- The transition from G2 to M is considered to be one of the most important
checkpoints in the cell cycle
Tumors
- Neoplasm:
o Benign: contain well-differentiated cells that cluster together in a single mass;
grows by expansion without invading other tissues
o Malignant: less well-differentiated and have ability to break loose, enter
circulatory or lymphatic system and form secondary malignant tumors at other
sites; compress blood vessels and outgrow their own blood supply causing
ischemia and tissue necrosis
- Examples of Benign Neoplasms:
o Adenoma, Osteoma, Papillomas, Fribromas, Lipomas, Meningiomas,
Hemangiomas
- Examples of Malignant Tumors
o SCC, Adenocarcinoma, Carcinoma, Sarcoma, Fibrosarcoma, Liposarcomas,
Osteosarcomas, Neuroblastomas, Meningeal Sarcomas, Leukemias,
Hemangiosarcomas
Cancer Cell Differentiation
- Anaplasia: used to describe the loss of cell differentiation in cancerous tissues
- The closer the tumor cells look to a normal cell, the lower the grade
- Grade 1 Neoplasms: WELL differentiated
- Grade 5: POORLY differentiated and display marked anaplasia
Methods by Which Cancer Spreads- Direct invasion and extension
- Seeding of cancer cells in body cavities
- Metastatic spread through the blood or lymph pathways
- “Seeding”: occurs when a tumor sheds cells into these spaces
o Seen often in peritoneal cavity with ovarian cancer and can be seen in pericardial
cavity
o This is often a complication postoperatively after removal of cancers
Genes that Control Cell Growth and Replication
*KNOW THIS
- **Proto-oncogenes: a gene involved in normal cell growth
o Normal genes that become cancer causing oncogenes if mutations occur
o Bypass apoptosis
o **Mutations cause them to become oncogenes, which cause the growth of
cancer cells
- TSG: inhibit the proliferation of cells in a tumor
- Grading: according to histologic or tissue characteristics
- Staging: spread of disease
*KNOW THIS
- **Angiogenesis: the development of new blood vessels that must occur in order for
tumors to enlarge as this supplies the tumor with blood vessels necessary for survival
o **Angiogenesis is needed for metastasis
- Radiation: kills cancer cells or slows growth by damaging their DNA
o Radiation also damages healthy cells
o It targets tumors specifically, but it is not systemic like chemo so it has fewer side
effects
o Unfortunately, radiation therapy negatively affects normal tissue that is rapidly
proliferative similar to malignant cellso Tissues within the treatment fields that are most frequently affected are the skin,
the mucosal lining of the GI tract, and the bone marrow
*KNOW THIS: be familiar how these agents work
Direct and Indirect DNA-Interacting Agents:
- Direct DNA-Interacting Agents: include alkylating agents, antitumor antibiotics, and
topoisomerase inhibitors
o The Alkylating Agents exert their cytotoxic effects by transferring their alkyl
group to many cellular constitutes
- Indirect DNA-Interacting Agents: include the antimetabolites and mitotic spindle
inhibitors
o The antimetabolites (folic acid antagonists and purine and pyrimidine antagonists)
interrupt the biochemical pathways relating to nucleotide and nucleic acid
synthesis
*KNOW THIS: be familiar how these agents work
Targeted Therapy:
- Target Cancer Therapy: uses drugs that selectively attack malignant cells without
causing harm to normal cells
- It focuses on altered molecules and signaling pathways that allow cancer cells to grow
and spread in an uncontrolled manner
- Targeted therapies include small molecules that block specific enzymes and growth
factors involved in cancer cell growth
*KNOW THIS
**Characteristics of Childhood Cancer
- Most involve the hematopoietic system, nervous system, or connective tissue (soft
tissue, bone, or kidney)
- Heritable forms of cancer tend to have
o An earlier age of onset
o Higher frequency of multifocal lesions in a single organ
o Bilateral involvement of paired organs or multiple primary tumors*KNOW THIS: be familiar with types of solid tumors in childhood; rare but remain 2nd
leading cause of death among school aged children in US
Common cancers in children are:
- Brain and Nervous System Tumors – first most common
- Neuroblastoma – second most common
- Wilms Tumor (Nephroblastoma – tumor of kidney)
- Rhabdomyosarcome
- Embryonal Sarcoma
- Retinoblastoma
- Leukemia
- Non-Hodgkin and Hodgkin Lymphomas
- Bone Cancers (Osteo and Ewing Sarcomas)
- **A change in blood cell production is a warning sign of cancer in children, leading to
more frequent and severe infections, fatigue, and paleness
- **Neuroblastoma - child has a WHITE REFLEX in children
- Radiation is NOT a common treatment for CHILDHOOD cancer
Chapter 7: Stress & Adaptation
*KNOW THIS:- **Hemostasis: from the Greek word “same” and “steady”; refers to any process that
living things use to actively maintain fairly stable conditions
- The VERY TIGHTLY/CONTROLLED/PURPOSEFUL maintenance of stable
internal involvement that a “healthy” body strives to maintain
- State of steady internal physical and chemical condition maintained by living systems
*KNOW THIS: understand mechanism of negative feedback
- *Negative Feedback: when the monitored function or value decreases below the set
point of the system, the feedback mechanism cause the function or value to increase
- When the function or value is increased above the set point, the feedback mechanism
causes it to decreased
- This is the feedback mechanism for adaptation to stress-
Definitions of Stress & Adaptation
*KNOW THIS: know the definition and difference
- Stress: a state manifested by symptoms that arise from the coordinated activation of the
neuroendocrine and immune system (general adaptation syndrome)
o A state manifested by a specific syndrome of the body developed in response to
any stimuli that made an intense systemic demand on it
o Can be measured by ECG of the heart, BP, biochemical analyses hormone level,
measurements of urinary and plasma catecholamines, cortisol levels obtained
from salivary samples, blood cells to obtain immune cell (lymphocyte) counts
- Adaptation: the ability to respond to challenges of physical or psychological
homeostasis and to return to a balanced state
o Mechanisms that evolved for organisms to respond to or modify their
environments, habits, or both to achieve a way of life that is best suited for
their needs
o A lot of factors can affect your body’s ability to adapt (age, health status,
nutrition)
o ** If you are exhausted and haven’t been eating well and are overall feeling
very stressed out
**These factors can affect your body’s ability to adapt and return to
homeostasis*KNOW THIS: different types of stressors
- Endogenous Stress: comes from within the body
- Exogenous Stress: comes from outside stress
o Eustress: normal or psychological stress interpreted as being beneficial for the
experience
Positive experience: getting married or having a baby
o Distress: negative wear and tear on the body which makes it susceptible to
disease
*KNOW THIS:
- **Allostasis: the process by which the body responds to stressors in order to regain
homeostasis
o Mechanisms that respond:
Immune system
Endocrine system
Musculoskeletal system
Physiologic and Anatomic Reserve
*KNOW THIS: the difference between the two
- Physiologic Reserve: the ability of the body systems to increase their function given the
need to adapt
o RBCs and O2 (Hg and Hct)
o Liver cells and nutrient storage
o Bone and calcium storage
- Anatomic Reserve: paired organs that are not needed to ensure continued existence and
maintenance of the internal environment (**structural adaptation)
o You only need ONE lung, kidney, and adrenal to survive
o If one is damaged, you can survive without the other*KNOW THIS: some characteristics of PTSD
Posttraumatic Stress Disorder (PTSD):
- PTSD: chronic activation of the stress response as a result of experiencing a potentially
life-threatening event
- Cause by major catastrophic events
o Major weather-related disasters, airplane crashes, terrorist bombings, and rape of
child abuse
- **Characteristics of PTSD:
o Intrusion: the occurrence of “flashbacks” during the waking hours or
nightmares in which the event is relived, often in vivid and frightening detail
o Avoidance: the emotional numbing that accompanies this disorder and disrupts
important personal relationships
o Hyperarousal: the presence of increased irritability, difficulty concentrating,
exaggerated startle reflex, and increased vigilance and concerned over safetyChapter 8: Disorders of Fluid, Electrolyte, & Acid-Base Balance
Distribution of Body Fluids:
- Intracellular Compartment (ICF): consists of fluids contained within all the billions of
cells in the body
o 2/3 of the body water in health adults
o High concentrations of Potassium
o **Potassium is responsible for regulating the resting membrane potential
- Extracellular Compartment (ECF): consists of fluids outside the cells, including that in
the interstitial or tissue spaces and blood vessels
o 1/3 of remaining body water
o Higher concentration of Sodium
Diffusion & Osmosis:
*KNOW THIS
- Diffusion: the movement of charged or uncharged particles along the concentration
gradient from an area of higher concentration to lower concentration
- **Osmosis: the movement of water across a semi-permeable membrane from the side
of the membrane with the lesser number of particles and greater concentration of water to
the side with greater number of particles and lesser concentration of water
- The osmotic pressure is equal to the hydrostatic pressure needed to oppose water
movement across the membrane
Edema:
*KNOW THIS
- Edema: accumulation of fluid is extracellular space; water goes to path of least
resistance
o When patient is sitting all day and LE swell and then you lay them in the bed
the edema resolves
o Pitting edema
o Nonpitting edema
o Brawny edema
- Physiologic Mechanisms that Contribute to Edema:o Increased the capillary filtration pressure
o Decrease the colloidal osmotic pressure
o Increase capillary permeability
o Produce obstruction to lymph flow
- Assessing Edema:
o Daily Weights
o Visual Assessment
o Measurement of Affected Part
o Application of Finger Pressure to Assess for Pitting Edema
Physiologic Mechanisms Assisting in Regulating Body Water
*KNOW THIS: know that thirst is a regulator of water intake and ADH regulates water
output
- **Thirst: primary regulator of water intake
o Sensory neurons called osmoreceptors which are located in the thirst center in
or near the Hypothalamus, respond to changes in ECF extracellular fluid
osmolality by swelling or shrinking
o Thirst normally develops when there is as little as a 1-2% change in serum
osmolality
o Thirst is one of the earliest symptoms of hemorrhage and often is present before
other signs of blood loss appear
o **Thirst is a regulator of water intake
- **Antidiuretic Hormone: a regulator of water output
o Also known as “vasopressors”
o ADH levels are controlled by ECF volume and osmolarity
- Both mechanisms respond to changes in extracellular osmolality and volume
Disorders of ADH Expression
** KNOW THIS
- **Diabetes Insipidus: deficiency of or a decreased response to ADH; too little ADH
o Disorder of salt and water metabolism and is marked by intense thirst and heavy
urination
o It is caused by a hormonal abnormality and isn’t related to DM
o The large urine output is accompanied by excessive thirst
o As long as thirst mechanism is normal and fluid is readily available, there is little
or no alteration in the fluid levelso Problems occur in patients who are unable to communicate the need for water or
unable to get water, and this causes hypertonic dehydration and increased
serum osmolality
- **Syndrome of Inappropriate Antidiuretic Hormone: failure of the negative feedback
system that regulates the release and inhibition of ADH; too much ADH
o In people with this syndrome, ADH secretion continues even when serum
osmolality is decreased, causing marked water retention and dilutional
hyponatremia
o **SIADH is a failure of the negative system that regulates and inhibition of
ADH
Regulators of Sodium
*KNOW THIS:
- **Kidneys are main regulators of sodium
o Kidneys RETAIN sodium when arterial pressure is DECREASED
o Kidneys ELIMINATE sodium when arterial pressure is INCREASED
- Assessment of Body Fluid Loss
o Tachycardia, hypotension, decreased vein filling and increased vein refill time
o **In infants, you can see depressed fontanel or sunken eyes if there is a loss of
body fluid
Potassium Distribution and Regulation
*KNOW THIS:
- **Extracellular concentration of Potassium: 3.5 – 5.0 mEq/L
- Potassium directly affects membrane potential
*KNOW THIS:
Severe Hypokalemia: when K 3.5
- There may be muscle paralysis with life-threatening respiratory insufficiency
- Quadricepts more prominently affected
- Cardiac arrythmiasSevere Hyperkalemia: when K 5.0
- Most common cause is decreased renal function
- IV solutions that contain potassium should never be started until the urine output has
been assessed and renal function has been determined adequate
- The first symptoms associated with hyperkalemia is paresthesis/numbness and
tingling in fingers and toes
- Generalized muscle weakness or dyspnea due to respiratory muscle weakness
- Irregular HR/Cardiac Arrythmias because K is central to establishing and
maintaining the resting membrane potential of cardiac muscle cells – helps it keep
beating at the right pace
*KNOW THIS
Disorders of Acid-Base Balance
- You must determine whether the metabolic acidosis is due to Bicarbonate loss or Acidic
gain
- *Metabolic Acidosis: is caused by a pH decrease (pH 7.35) (increase in acidity) and a
Bicarbonate decrease (HCO3 22)
o Anytime there is an increase in acid, there is a decrease in Bicarb
o Bicarb loss: caused by diarrhea or renal problems
o Acid increase: caused by the addition of another acid into the serum (aspirin
toxicity, insufficiency of kidneys, carbs not metabolized)
o Acid Gain is usually grouped under the mnemonic MUDPILES
Methanol (wood grain alcohols)
Uremia
Diabetic Ketoacidosis
Paraldehyde
Isoniazid or iron
Lactic acid
Ethylene glycol
Salicylates
o Symptoms:
Tachypnea – Kussmaul breathing (body is trying to expel CO2)
Respiratory system tries to compensate by expelling CO2;
hyperventilation
Compensatory: you will see a decrease in CO2 because body is trying to
expel
o Treatment: supplement sodium bicarb is mainstay of treatment- *Metabolic Alkalosis: is caused by a pH increase (pH 7.45) (more alkalotic) and a
Bicarbonate increase (HCO3 26)
o Anytime there is a decrease in acid, there is an increase in Bicarb
o Hyperaldosterone, vomiting and NG suction, loop diuretics, alkai ingestion
o Symptoms:
Slow respirations (RR 12); you will see hypoventilation
Compensatory: you will see high CO2 because body is trying to keep
increasing the acidity of body (CO2 is acidic) to help bring down Bicarb
Many people have no symptoms or may have signs related to volume
depletion or hypokalemia
If neurological manifestations do occur, they include mental confusion,
hyperactive reflexes, tetany and caropedal spasms
Severe metabolic alkalosis can cause respiratory failure, cardiac
arrythmias, seizures and coma
- Normal pH: 7.35 – 7.45
- Normal Bicarb: 22 – 26
- Normal PCO2: 35 – 45 mm
- **Metabolic Acidosis: pH is low, Bicarb (HCO3) is low, and CO2 is low
- **Metabolic Alkalosis: pH is high, Bicarb (HCO3) is high, CO2 is high
Anion gap: evaluates states of metabolic acidosis by measuring the gab or difference between
the negatively charged and positively charged electrolytes- Respiratory Acidosis: is caused by a decrease in pH (pH 7.35) and increase in PCO2
(PCO2 45 mm)
o Occurs in acute or chronic conditions that impair effective alveolar ventilation
(Hypoventilation) and cause an accumulation of PCO2 (Partial Pressure of
Carbon Dioxide)
o Symptoms:
Bradypnea: anything that is affecting the body’s ability to breath
normally (hypoventilation causes the body to not expel PCO2 properly)
Mild forms can cause warm, flushed skin, weakness and tachycardia
Elevated levels of CO2 produce vasodilation of cerebral blood vessels
causing headaches, blurred vision, irritability, muscle twitching and
psychological disturbances
Can cause increase in CSF
o Treatment:
Improving ventilation
o Compensatory: Kidneys will try and release Bicarb (HCO3 26) to help increase
pH levels
- Respiratory Alkalosis: is caused by increase in pH (pH 7.45) and decreased in PCO2
(PCO2 35)
o Hyperventilation or respiratory rate in excess of that needed to maintain normal
plasma PCO2 level
o Symptoms:
Tachypnea: hyperventilation causes the body to become alkalotic because
you are breathing off PCO2 (which is acidic)
Hyperexcitability of nervous system and decrease in cerebral blood flow
Light headedness, dizziness, tingling, numbness of fingers and toes
Sweating, palpations, panic, air hunger
o Treatment:
Breathing into a paper bag
o Compensatory: Kidneys will excrete all this HCO3 through the urineChapter 25: Structure and Function of Cardiovascular System
Route of the blood through the heart:
*KNOW THIS
- Basic Circulatory Circuit: Deoxygenated blood from the right side of the body travels
to the right heart via the venous system
o Right is Receiving
o The right heart pumps this blood to the lungs via the Pulmonary Artery
- The lungs oxygenate the blood and send it to the left side of the heart through the
Pulmonary Veins
o This oxygenated blood is pumped by the left heart through the Aorta to the rest
of the body
o Pumped by Left Heart through Aorta
o Left is Leaving the Heart to rest of the body
- Right side pumps blood to lungs (Pulmonary Circulation)
- Left heart pumps blood to rest of body (Systemic Circulation)
- Arteries move oxygenated tissues to blood
- Capillaries are exchange system where transfer of gases, nutrients, and wastes take place
- Veins return deoxygenated blood to the heart
Circulatory System Pressure:*KNOW THIS
- Venous Pressure: propels blood through the lungs (Pulmonary Circulation)
- Arterial Pressure: propels blood to all tissues of the body (Systemic Circulation)
*KNOW THIS
- Laplace Law: describes the relation between wall tension, transmural pressure, and
radius
o States wall tension becomes greater as radius decreases
o Wall tension is also affected by wall thickness; it increases as the wall becomes
thinner and decreases as the wall becomes thicker
*KNOW THIS
- Compliance: the ability of a vessel to respond to an increase (or decrease) in pressure by
distending to increase (or decrease) the amount of volume it can hold; without recoiling
back to original size
o **A vein is 24x more compliant than a corresponding artery
Due to thinner walls
Cardiac Cycle:
*KNOW THIS
- *Systole: the period during which the ventricles are contracting
- *Diastole: the period during which the ventricles are relaxed and filling with blood
Cardiac Output:
*KNOW THIS
- **Cardiac Output: amount of blood the heart pumps each minute OUT OF THE
HEART; does NOT measure systemic flow through arteries and veins
o **CO = SV x HR
Stroke Volume x Heart Rate
- Blood Pressure = Cardiac Output x Peripheral Vascular Resistance
o CO is variable
o BP is variable but to lesser degree
o PVR is regulated by baroreceptor reflex in order to maintain pressure and
perfusionStructure and Function of the Microcirculation:
KNOW THIS
- Arterioles: resistance vessels for circulatory system
- **Capillaries: microscopic vessels that connect the arterial and venous segments;
interstitial fluid exchange
o Controlled by hydrostatic and osmotic pressures
o **Allow O2, nutrients, CO2, and waste products to pass to and from tissue
cells
o In the lungs, capillaries and alveoli’s is where gas exchange takes place
- Venules
- Edema: excess interstitial fluid in tissues
o Imbalance of any of the factors that control movement of water between the
vascular compartment and the tissue spaces
o Disproportionate increase in capillary fluid pressure or permeability, decreased
capillary colloidal osmotic pressure, or impaired lymph flow
- Baroreceptors: monitor BP
- Chemoreceptors: oxygenation, CO2 and pH
- Osmotic and Hydrostatic Forces:
o Capillaries
o Veins
o Arteries
o Lymphatic system
o VenulesChapter 26: Disorder of Blood Flow and Pressure Regulation
- Endothelium: is a multifunctional tissue that plays an active role in controlling vascular
function
o It is a semipermeable membrane that plays an essential role in maintaining
homeostasis
o The endothelium maintains proper dilation and constriction of blood vessels, this
largely determines a patient’s blood pressure
- Endothelial Dysfunction: is a condition in which the endothelial layer (the inner lining)
of the small arteries fails to perform its important functions; potentially reversible
- Endothelial dysfunction can be caused by HTN, diabetes, smoking, aging, physical
inactivity, and family history of premature atherosclerotic disease
- Whenever there is a cause, SMOKING will always be on the list
*KNOW THIS
- **Smoking a pack a day or more per day DOUBLES the damage to endothelium
- Quitting smoking reduces the risk of endothelial damage significantly
Mechanisms of BP Regulation
- Arterial blood pressure: represents the force that distributes blood to the capillaries
throughout the body
*KNOW THIS
- Systolic Pressure: Ventricular Contraction
o The highest arterial pressure is the systolic pressure
- This represents the volume of blood ejected from the ventricles with each beat, the rate
and force with which the blood is ejected, and the elasticity of the aorta and large arteries
- Systolic pressure often increases with aging as the aorta and large arteries lose their
elasticity and become more rigid
- Diastolic Pressure: Ventricular Relaxation
o Is the lowest pressure and reflects the closure of the aortic valve, the energy that
has been stored in the elastic fibers of the large arteries during systole, and the
resistance to flow through arterioles into the capillariesDisorders of Arterial System
- Dyslipidemia refers to the imbalance of lipid components in the blood
o Since elevated lipids are a risk factor for developing atherosclerosis, maintaining
low lipids is one goal of prevention of atherosclerotic disease
Triglycerides: energy metabolism
Phospholipids: important structural constituents of lipoproteins, blood
clothing components, the myelin sheath and cell membranes
Cholesterol: chemical activity similar to other lipid substances
Hyperlipidemia: elevated levels of one or all the above
- **Atherosclerosis (hardening of the arteries): denotes the formation of fibrofatty
lesions in the intimal (innermost) lining of the large and medium arteries such as the
aorta, coronary arteries and large vessels of the brain
o The main risk is hypercholesterolemia, specifically high LDL
o Hypercholesterolemia can be treated with diet and medications but there are some
factors such age, family history and gender (being male is a considered a risk
factor) that can’t be altered
o Men are at greater risk than pre-menopausal women for atherosclerotic coronary
vascular disease
o After menopause the incidence of atherosclerotic-related diseases increases and
the risk for MI is about the same
- Other risk factors for atherosclerosis are:
- Smoking, obesity and visceral fat, HTN, DM
- **Smoking a pack a day or more per day doubles the damage to endothelium
- **Quitting smoking reduces the risk of endothelial damage significantly
*KNOW THIS
- Goal is to have LOW levels of LDL and HIGH levels of HDL
- **LDL: bad cholesterol
o This is because LDL largely carries cholesterol to the periphery where it may be
incorporated into atherosclerotic lesions- **HDL: good cholesterol
o HDL mostly transports cholesterol back to the liver from the periphery for
metabolic breakdown
*KNOW THIS: difference between the two
- Dyslipidemia: serum cholesterol 240 or greater
o Primary Dyslipidemia: is inherited (familial)
Describes elevated cholesterol levels that develop independent of health
problems or lifestyle behaviors
o Secondary Dyslipidemia: caused by unhealthy lifestyle
*KNOW THIS: know about development of atherosclerosis
- **Atherosclerosis: the main risk factor is hypercholesteremia, specifically HIGH LDL
o Hardening of the arteries
o Denotes the formation of fibrofatty lesions in the intimal (innermost) lining of
the large and medium arteries such as the aorta, coronary arteries and large
vessels of the brain
- Fatty streaks
o Thin, flat yellow intimal discolorations that progressively enlarge
- Fibrous atheromatous plaque
o The accumulation of intracellular and extracellular lipids, proliferation of vascular
smooth muscle cells, and formation of scar tissue
- Complicated lesion
o Contains hemorrhage, ulceration, and scar tissue deposits
- Major Risk Factors:
o Smoking
o HTN
o Family History
o Age (men 45 years, women 55 years)
o HDL 40
o CRP Levels
- C-Reactive Protein: is an acute phase reactant protein of the inflammation process, it is
made in the livero The CRP levels increase when there is a condition causing inflammation
somewhere in the body. It is nonspecific, in addition to inflammation of the
arteries of the heart, CRP can be elevated with some types of infections,
inflammatory bowel disease, in auto-immune disorders like lupus and RA
Arterial Involvement in Atherosclerosis
*KNOW THIS know the important complications in large and mediums sized arteries
- **Medium-sized arteries: the important complications are those of:
o Ischemia and infarction due to vessel occlusion
- **Large-sized arteries: the important complications are those of:
o Thrombus formation and weakening of the vessel wall
- Arteries supplying the heart, brain, kidneys, lower extremities, and small intestine are
most frequently involved
**KNOW THIS
Clinical Manifestations of Atherosclerosis
- Ischemia: Vessel occlusion can partially or totally block circulation (in medium
