Study Guide N230A Advanced Pathophysiology

Exam 1 Fall 2013

50 Multiple Choice test questions

5 Short Answer/Case Study questions

Multiple Choice
14 questions/Cellular adaptation & injury (Chapter 2):

1. Know effects of different cell injury

a. Hypoxia: Lack of sufficient oxygen; single most common cause of cellular injury. The
initial insult in hypoxic injury is usually ischemia
i. Ischemia = the cessation of blood flow into vessels that supply the cell with
oxygen and nutrients. Gradual onset allows for myocardial adaptation.
ii. Anoxia = total lack of oxygen - an acute obstruction can cause myocardial cell
death within minutes
iii. Effects: Decrease in ATP, causing failure of sodium-potassium pump and
sodium calcium exchange; cellular swelling; continual loss of essential
enzymes, proteins and ribonucleic acids through the very permeable
membrane of the cell. Increased glycolysis decreases the pH, leading to
protein denaturation, nuclear chromatin clumping and lysosomal swelling and
enzyme release and cellular digestion. Reperfusion injury is caused by
restoration of oxygen and is concerned with transplants and in myocardial,
hepatic, intestinal, cerebral, renal and other ischemic syndromes. During
reperfusion with oxygen, free radicals are released and increase in cell/tissue
damage.
iv. Other causes
1. lack of oxygen in the air
2. loss of hemoglobin or hemoglobin function
3. decreased production of red blood cells
4. diseases of respiratory and cardiovascular systems
5. poisoning of the oxidative enzymes (cytochromes)
b. Radiation-Ionizing radiation: any radiation removing orbital electrons from atoms.
Ex: x-rays, gamma rays, alpha/beta particles
i. direct: cells targeted affect DNA and cells with rapid mitosis i.e. skin cells,
testicular seminiferous epithelium, intestinal mucosa, ovarian follicles, stem cell
ii. indirect: damage to cells after the initial radiation; usually around the injured
cell or cells that replicate from the damaged cell.
iii. Effects can be acute or delayed
1. Acute - skin redness, skin damage
2. Delayed - somatic (leukemia, cancers), genetic (mutations in offspring),
fetal (damage to fetus)
iv. Greatest sensitivity is when the cell is in G2 phase
c. Free radical damage: Membrane damage; difficult to control and initiate chain
 reactions. May be initiated within cells by absorption of UV light or x-rays, oxidative
reactions that occur during normal metabolism and enzymatic metabolism of
exogenous chemicals or drugs.
i. Free radicals can cause
1. lipid peroxidation or the destruction of unsaturated fatty acids
2. alterations of proteins causing fragmentation of polypeptide chains
3. alterations in DNA by breakage of single strands
ii. A free radical is an electrically uncharged atom or a group of atoms having an
unpaired electron. To gain stability, the radical gives up an electron to another
molecule or steals an electron. These radicals can bond with proteins, lipids
and carbohydrates, key molecules in membranes and nucleic acids.
iii. Reactive Oxygen Species (ROS) - a type of free radical that causes oxidative
stress when there’s excess ROS → overwhelms the body’s antioxidant system
causing membrane damage and mitochondrial overload.
iv. Free radicals major role in initiation and progression of cardiovascular diseases
such as hypertension, ischemic heart disease, chronic heart failure,
hyperlipidemia, and also diabetes mellitus.

2. Differentiate different types and causes of necrosis:

a. Necrosis: is the sum of the changes after local cell death and includes the processes
of inflammation and cellular autolysis (self-digestion).
i. accidental cell death that occurs after severe and sudden injury
ii. signs of irreversible injury and progression towards necrosis:
1. clumping and disruption of genetic material
2. disruption of plasma membrane and organelle membranes
iii. in later stages of necrosis most organelles are disrupted
1. karyolysis - nuclear dissolution and chromatin lysis due to hydrolytic
enzymes (irreversible)
2. pyknosis - clumping of the nucleus (cell nucleus shrinks and becomes
small, dense mass of genetic material)
3. karyorrhexis - fragmentation of the nucleus into smaller particles or
“nuclear dust”; allows for clean up by neighboring cells
b. Five Types of Necrosis: 1. Caseous 2. Coagulative 3. Liquefactive 4. Fat 5.
Gangrenous Necrosis
i. Caseous:
1. Cause: Commonly results from tuberculous pulmonary infection,
particularly by Mycobacterium tuberculosi; is a combination of
coagulative and liquefactive necrosis.
2. Where is it found: tuberculosis pulmonary infections
3. What does it look like: Tissues appear soft and granular and resemble
clumped cheese, which gives this type of necrosis its name.
ii. Coagulative:
1. Cause: Protein denaturation. Commonly results from hypoxia caused by
 severe ischemia or hypoxia caused by chemical injury (especially
ingestion of mercuric chloride)
2. Where is it found: kidneys, heart, adrenal glands
3. What does it look like: Protein denaturation causes protein albumin to
change from a gelatinous, transparent state to a firm, opaque state,
similar to that of a cooked egg white.

iii. Liquefactive
1. Cause:
a. Ischemic injury to neurons and glial cells; hydrolase
b. bacterial infections (staph, strep, and E. coli) - in these cases,
hydrolases are released from lysosomes of neutrophils
2. Where is it found: brain
3. What does it look like: As the cells are digested by their own
hydrolases, the tissue becomes soft, liquefies, and is walled off from
healthy tissue, forming cysts.

iv. Fat
1. Cause: cellular dissolution caused by powerful enzymes called lipases.
Lipases break down triglycerides, releasing free fatty acids, which then
combine with calcium, magnesium, and sodium ions, creating soaps (a
process known as saponification)
2. Where is it found: breast, pancreas, and other abdominal structures;
places where you would find a great deal of fat
3. What does it look like: opaque and chalk white

v. Gangrenous Necrosis: preludes to gangrene: A term used in surgical

clinical practice, refers to death of tissue.
1. Cause: Death of tissue, results from severe hypoxic injury commonly
occurring because of arteriosclerosis of major arteries (esp. in the lower
leg), followed by bacterial invasion.
a. Dry Gangrene: coagulative necrosis; Skin is dry, shrinks, results
in wrinkles, and color changes to black or dark brown.
b. Wet Gangrene: Develops when neutrophils invade the site,
causing liquefactive necrosis. Usually occurs in internal organs,
causes site to become cold, swollen, and black. Pus produces a
foul odor and death can ensue if systemic symptoms are severe
enough. Diabetic patients.
c. Gas Gangrene: Caused by infection of injured tissue by one of
many species of Clostridium. These bacteria are anaerobic and
produce hydrolytic enzymes and toxins that destroy connective
tissue and cellular membranes. They also cause gas bubbles to
form in muscle cells. This can be fatal if enzymes lyse the
membranes of red blood cells, destroying their capability to carry
 oxygen. Death is the result of shock. Gas gangrene is a special
type of gangrene and is treated with antitoxins and supplemental
oxygen delivered in a hyperbaric chamber.

3. Effects of cell breakdown including hemosiderin deposits

a. Hemosiderin: yellow-brown pigment derived from hemoglobin
b. Effects of cell breakdown: phagocytosis by macrophages. red blood cells break down
and hemosiderin accumulates, resulting in the release of the iron in the heme
c. Accumulation of hemosiderin often occurs in areas of bruising and hemorrhage and in
the lungs and spleen after congestion caused by heart failure.

4. Examples of how these occur in tissues and the differences between:

a. Hyperplasia: is an increase in the number of cells resulting from an increased rate of
cellular division; controlled response to stimulus ceases after stimulus removed
i. What tissues:
1. Compensatory Hyperplasia: Epidermal and intestinal epithelia,
hepatocytes, bone marrow cells, and fibroblasts (and some hyperplasia
is noted in bone, cartilage and smooth muscle cells) Enables organs,
such as the liver, to regenerate after a loss of substance.
2. Hormonal Hyperplasia: estrogen dependent organs (uterus and breast)
3. Pathologic Hyperplasia: abnormal hyperplasia resulting from excess
hormone secretion; endometrium
b. Hypertrophy: increases cell size and size of the affected organ allows cell to achieve
an equilibrium between demand and function. Increase in cell components related to
an increased rate of protein synthesis; may be related to limitations in blood flow
i. What tissues:
1. Striated muscles of the heart and skeletal muscles: can be pathologic or
physiologic response (the cells cannot adapt to the increase in
metabolic demands by mitotic division so they instead enlarge);
Myocardial hypertrophy can lead to heart failure.
2. Epithelial tissues of the kidneys (ex. when a kidney is removed)
c. Dysplasia: abnormal changes in size, shape, appearance and organization of mature
cells (aka atypical hyperplasia). It is possibly reversible after the irritating cause has
been removed. Dysplasia does not indicate cancer and may not progress to cancer.
i. What tissues:
1. Epithelial tissue of the cervix, oral cavity, and respiratory tract: they are
strongly associated with neoplastic growths and adjacent to cancerous
cells (In females, changes may progress to breast neoplastic disease)
2. Associated with persistent severe chronic irritation or injury. Caused by
herpetic lesions (and other causes)
d. Metaplasia: reversible replacement of one mature cell by another (sometimes by a
less differentiated cell type). It allows for replacement with cells that are better able to
tolerate environmental stresses. The type of cell that replaces it must be within its
same tissue class. (epithelial cells cannot change to connective tissue cells)
 i. What tissues:
1. Epithelial cells of the bronchial airway lining (Smoking induces
replacement of columnar ciliated epithelial cells with stratified squamous
epithelial cells that can’t secrete mucous- loses protective function)
2. Associated with chronic irritation or injury (less extreme than Dysplasia)
e. Atrophy: is a decrease or shrinkage in cellular size. Atrophy in a sufficient number of
organ’s cell, the entire organ then also shrinks or becomes atrophic.
i. What tissues: Organs/Tissues (heart, secondary sex organs, the brain, skeletal
muscles)
ii. Mechanism: ↓ protein synthesis, ↑ protein catabolism, or both.
iii. Lack of use (bedridden) is disuse atrophy. Also associated with aging,
malnutrition, denervation (occurs in paralyzed limbs), lack of endocrine
stimulation, ischemia and other diseases

5. Characteristics of apoptosis (p. 84)

a. What is it: An active process of cellular self-destruction (programmed cell death).
Unlike necrosis, apoptosis affects scattered, single cells and results in shrinking of a
cell; whereas in necrosis, cells swell and lyse.
b. Implicated in: normal and pathologic tissue changes
c. How it works:
i. Generally:
1. Cell Receives Apoptotic Signal
2. Initiator Caspase
3. Effector Caspase- cuts up other proteins in the cell
4. Death Substrates
5. Simultaneously signals Apoptosis:
a. Disablement of DNA repair and cell survival proteins
b. Condenses chromosome and fragment DNA
c. Disassembles cell structure
ii. Specifically (as per the videos from class, not sure how much we need to
know) an inhibitory signal is initiated through a series of controlled chain
enzymatic reactions to inhibit the bcl-2 protein(which inhibits apoptosis) in the
mitochondrial membrane to function)
1. Killer T cell approaches the diseased cell
2. When the plasma membranes of both cells come together, the death
ligand of the killer T cell attaches to the death receptor of the diseased
cell, which then moves into the diseased cell’s cytoplasm
3. Adaptor proteins then attach, and procaspase 8 is recruited
4. Caspase 8 is then activated and released , which in turn activates
Caspase 3
5. After this point the rapid breakdown of other proteins inside the cell by
the caspase occurs
6. The growing signal cascade then approaches the mitochondria, which
stimulates the mitochondria to release cytochrome-c
 7. The cytochrome-c then activates Apaf-1, which recruits Caspase 9, to
create the apoptosome
8. The apoptosome activates caspase 3, which then in turn cleaves the
actin cytoskeleton (which is made of proteins)
9. The cell is then broken down and “repackaged”, where they are then
engulfed by phagocytes
EG: Prion PC (a protein) kills by signaling apoptosis in neuronal cells

16 questions/Fluid & electrolytes (Chapter 3):

6. Know regulation, effects, and abnormalities, and cause of abnormalities for Na+, K+,
and Ca++:
General Guidelines/Concepts for Sodium and Water:
● Sodium - most abundant ECF cation
○ Regulated by Renal effects of Aldosterone from the adrenal cortex and natriuretic
peptides
○ Renin-Angiotensin-Aldosterone system - when blood volume or blood pressure is
low, aka Blood Flow to the glomerulus (kidneys) drops → Juxtaglomerular cells (in
kidney) secrete Renin into the bloodstream → Renin travels to the liver → Renin
converts Angiotensinogen in the liver to Angiotensin I → Angiotensin I travels to the
lungs → Angiotensin I is converted into the lungs into Angiotensin II → Angiotensin II
travels to the adrenal glands → Angiotensin II stimulates the adrenal glands to produce
Aldosterone → Aldosterone causes the kidneys to retain Sodium and water → Sodium
and water retention leads to increase in fluid volume and sodium levels
■ Angiotensin has 2 purposes
● Stimulates Aldosterone secretion
 ● Vasoconstriction - Elevate systemic blood pressure and restores renal
perfusion
■ The restoration of sodium levels and fluid volume INHIBITS further renin
release
○ Natriuretic peptides - atrial natriuretic peptide (ANP) and brain natriuretic peptide
(BNP) - DECREASE blood pressure and INCREASE sodium and water secretion, aka
antagonists to the Renin-Angiotensin-Aldosterone system
● Water
○ Regulated by antidiuretic hormone ADH from posterior pituitary
○ Figure 3-4 page 102 of text: When increased Plasma Osmolality or Decreased
Circulating Fluid Volume → Increased Thirst, Increased ADH Secretion, Increased Fluid
Intake, and Decreased Water Excretion → Increased Water Retention → Increased
Circulating Fluid Volume → Decreased Plasma Osmolarity → Decreased ADH and
Decreased Plasma Osmolarity → Decreased ADH and Decreased Thirst

a. Na+ (high) - Hypernatremia: (serum sodium levels >147 mEq/L) may be caused by an
acute increase in sodium or a loss of water. Normal levels 135-145 mEq/L. Water travels
from ICF → ECF [Cells Shrink aka Crenation]. Can be treated in clinical settings with
solution of water containing 0.9% NaCl (normal concentration in blood plasma) in order
to increase levels of water in the body.

i. Regulation: Chiefly by the RAA system. Release of Aldosterone from the

Adrenal gland causes kidneys to increase reabsorption of Na+ and H2O. ADH
effects H2O levels (influence Na+).
ii. Effects:
1. High [Na+] results in a hypertonic vasculature. Water moves from ICF
to ECF, resulting in cellular dehydration from increased osmotic
pressure.
2. Increased excitability of excitable cells (i.e. neurons, muscles).
Increased concentration of extracellular Na+ results in a steeper
gradient across the membrane. Threshold is achieved more quickly.
iii. Abnormalities:
1. Increased Na+
a. Seizures (excitability)
b. Coma, Confusion (cellular dehydration)
c. Pulmonary Edema (fluid excess)
d. Thirst, Fever, Dry membranes (cellular dehydration)
2. Water Deficit (Hypovolemia, Deprivation or Loss)
a. Weak Pulse, Tachycardia (= Rapid pulse), hypovolemia (from
 dehydration), Hypotension (workbook says hypertension, but
most likely causes hypotension due to hypovolemia)
b. Coma, Confusion, weight loss, irritability (cellular dehydration)
c. Thirst, Fever, Dry membranes (cellular dehydration)
iv. Cause of Abnormalities:
1. Inadequate free water intake
2. Inappropriate administration of hypertonic saline (IV)
3. Over-secretion of Aldosterone
a. Primary Hyperaldosteronism
b. Syndrome - cause excessive Adrenocorticotropic Hormone
(ACTH) which increases Aldosterone secretion
b. Na+ (low) - Hyponatremia: (serum sodium concentration <135 mEq/L) usually causes
movement of water into cells. [Water from ECF → ICF] … Cells Swell
i. Regulation: Chiefly by the RAA system. Release of Aldosterone from the
Adrenal gland causes kidneys to increase reabsorption of Na+ and H2O. ADH
effects H2O levels (influence Na+).
ii. Effects:
1. Decreases ECF osmotic pressure and water moves into cell. Na deficits
cause plasma hypoosmolality and cellular swelling.
a. Pure sodium deficits
b. Low intake
c. Hypoosmolar hyponatremia
2. Hypertonic hyponatremia- shift of water from ICF to the ECF as in
hyperglycemia, hyperlipidemia, and hyperproteinemia. Plasma increase
in glucose lipids or proteins displace water volume and dilutes sodium
and other electrolyte concentrations.
iii. Abnormalities:
1. Behavior and neurological changes
a. lethargy, headache, confusion, apprehension, seizures, coma,
absence of thirst, decreased body temperature, rapid pulse,
hypotension, nausea, vomiting
2. Pure Sodium loss- loss of ECF causing isotonic hypovolemia
a. hypotension, tachycardia, decreased urine output
b. hematocrit and plasma protein levels may be elevated, urine
specific gravity less than 1.010 when renal function is normal.
3. Dilutional hyponatremia eg SIADH- weight gain, edema, ascites, jugular
vein distension. Hyponatremia due to gaining water and things being
out of proportion is one example (SIADH), other kinds exist.
iv. Cause of Abnormalities:
1. Pure Sodium deficits caused by diuretics and extrarenal losses
(vomiting, diarrhea, gastrointestinal suctioning, or burns)
2. Inadequate intake- low sodium diet
3. Dilutional hyponatremia
 a. excess of TBW in relation to total body sodium diets.
b. shift of water from the ICF to ECF space
c. use of excess hypotonic saline
d. excess of sweating which stimulates thirst and water. Seen in
endurance exercise when only pure water is replaced
c. K+ (high) - Hyperkalemia: (potassium levels >5.5 mEq/L) may be caused by
increased potassium intake, (RARE). A shift of K+ from ICF to ECF, or decreased
renal excretion. Decrease in pH due to more H+ entering ICF.
i. Regulation:
1. Na+/K+ Pump
2. Kidneys … [Distal tubule urine flow]
3. Hormones:
a. Aldosterone → increased secretion of K+
b. Insulin → increases activity of Na+/K+ ATPase pump → K+ →
liver & muscle
c. Catecholamines: (epinephrine & norepinephrine)
[-𝛽1 - K+ → ICF] [-𝛼 - K+ → ECF]
ii. Effects / Abnormalities:
1. Paresthesia (tingling)
2. Increased Excitability
3. Diarrhea
4. Nausea
5. Metabolic Acidosis
6. Severe: Paralysis
7. Acute: Flaccid Paralysis
8. Muscle weakness is most common characteristic, or paralysis and
changes in the electrocardiogram. Mild attacks--neuromuscular
irritability may be manifested--tingling lips and fingers, restlessness,
intestinal cramping, and diarrhea. Severe--muscle weakness, loss of
muscle tone and paralysis.
iii. Cause of Abnormalities: Decreased renal function, increased intake or shift of
potassium from cells to ECF--from cell trauma or a change in cell membrane
permeability, acidosis, insulin deficiency, or cell hypoxia.
iv. Manifestations: Metabolic acidosis
d. K+ (Low) - Hypokalemia: (serum potassium concentration <3.5 mEq/L) indicates loss
of total body potassium, although ECF hypokalemia can develop without losses of total
body potassium and plasma K+ levels may be normal or elevated when total body
potassium is depleted.
i. Regulation:
1. Na+/K+ Pump
2. Distal tubule urine flow
3. Hormones:
 a. Aldosterone → increased secretion of K+
b. Insulin → Na+/K+ ATPase pump → K+ → liver & muscle
c. Catecholamines: -𝛽1 - K+ → ICF
-𝛼 - K+ → ECF
ii. Abnormalities:
1. Cardiac Irritability
2. Dysrhythmias
3. vomiting
4. paralytic Ileus (no peristalsis)
5. Thirst
6. Inability to concentrate urine
7. Decreased muscle excitability (RMP more negative with less K+)
iii. Cause of Abnormalities:
1. reduced potassium intake
2. increased ICF to ECF potassium concentration
3. loss of potassium from body stores
4. increased aldosterone secretion
5. increased renal excretion
iv. Manifestation: Metabolic alkalosis
e. Ca++ (high) - Hypercalcemia: (serum calcium concentration >10.4 mEq/L) can be
caused by a number of diseases, including hyperparathyroidism (overactive PTH main
cause), bone metastases, sarcoidosis, and excess vitamin D.
i. Regulation: 3 Hormones
1. Calcitonin (decreases plasma calcium)
2. Vitamin D (Increases calcium absorption)
3. Parathyroid Hormone (PTH) (Increases plasma calcium levels)
ii. Treatment: Rehydration, increase urinary excretion, administering oral
phosphates, calcitonin, and corticosteroids
iii. Effects: Muscle weakness, increased bone fractures, kidney stones,
constipation, brachycardia
iv. Abnormalities: (?) Increases block of sodium into the cell, which causes a
decrease in neuromuscular excitability. This makes the nerves less able to fire
signals. Threshold potential more positive and cell membrane loses
excitability. Shortened QT segment on ECG and depressed, widened T waves
v. Cause of Abnormalities:(?) Increased block of sodium due to high serum
calcium levels.
vi. Other Information: Calcium is located in the bone as hydroxyapatite.
vii. Used for the following:
1. Blood clotting
2. Bones and teeth
3. Cell receptor function
4. Hormone secretion
 f. Ca++ (low) - Hypocalcemia: (serum calcium concentration <8.5 mg/dl) is related to
inadequate intestinal absorption, deposition of ionized calcium into bone or soft tissue,
blood administration, or decreased PTH and vitamin D levels.
i. Regulation: Treat with oral calcium replacement. Decrease phosphate for long-
term management, severe symptoms can be treated with 10% intravenous
calcium gluconate
ii. Effects: Chvostek sign, Trousseau sign, convulsions, tetany (muscle spasm
that interferes with breathing), muscle cramps
iii. Abnormalities:
1. Increases the sodium going into the cell.
2. neuromuscular excitability so nerves fire more easily.
3. Depolarizes nerve and muscle so smaller stimulus is required for
initiation.
4. ECG has prolonged QT interval.
iv. Cause of Abnormalities:
1. Due to inadequate intestinal absorption,
2. Excessive deposition of ionized calcium into bone or soft tissue,
3. Blood transfusion
4. Vitamin D deficiency.

7. Water movement between ICF and ECF (osmosis, oncotic pressure, hydrostatic
pressure)
a. Osmosis: the movement of water “down” a concentration gradient, that is, across a
semipermeable membrane from a region of “higher” water concentration to a “lower”
water concentration. (p.27)
b. Oncotic Pressure: (aka colloid osmotic pressure) The overall osmotic effect of
colloids, such as plasma proteins (eg albumin), creates pressure by large molecules
such as plasma proteins that cannot penetrate the membrane and pulls water towards
the proteins. (p.28)
c. Hydrostatic pressure: the mechanical force of water pushing against cellular
membranes. Filtration is the movement of water and solutes through a membrane
because of a greater pushing pressure (force) on one side of the membrane that on
the other side. eg. In the vascular system, hydrostatic pressure is the blood pressure
generated in blood vessels by the contraction of the heart. Blood reaching the capillary
bed has a hydrostatic pressure of 25 to 30 mmHg, which is enough force to push water
across the thin capillary membranes into the interstitial space. (p.26)

8. Dehydration (signs and symptoms & people at risk) (pg. 104)

a. People at risk
i. Pure water deficits (hyperosmolar or hypertonic dehydration) are rare because
most people have access to water
ii. Individuals who are comatose or paralyzed continue insensible water losses
through the skin and lungs with a minimal obligatory formation of urine.
iii. Hyperventilation by fever also may precipitate water deficit
 iv. Obese people are at greater risk for dehydration than lean people because
adipose cells contain little water; fat is water-repelling
v. The most frequent cause of water loss is increased renal clearance of free
water as a result of impaired tubular function or inability to concentrate the
urine, as with diabetes insipidus
vi. Infants- Renal mechanisms (regulating fluid/ electrolyte conservation) may not
be mature enough to counter losses in body fluids causing rapid dehydration
(p.97)

b. Signs and symptoms

i. Headache, Thirst, Dry skin and mucous membranes, Elevated temperature,
Weight loss, and Decreased or concentrated urine (with the exception of
diabetes insipidus)
ii. Decreased skin turgor may be present
iii. Symptoms of hypovolemia (tachycardia, weak pulses, postural hypotension)
may be present
iv. In cases of moderate water loss, an elevated hematocrit and serum sodium
concentration may occur in addition to clinical signs and symptoms

9. stimulation of thirst perception (figure 3-4, page 102)

a. Thirst perception (created by Osmoreceptors) can be stimulated by:
i. dry mouth, plasma hyperosmolality, and plasma volume depletion (when water
loss equals 2% of individual’s body weight)
ii. osmoreceptors also stimulate release of ADH

10. Movement of Na and water in and out of cells in response to injury

a. (pg. 53) Injury leading to ischemia results in reduced mitochondrial oxygenation and
thus reduced ATP production. This causes the plasma membrane’s sodium-potassium
pump and sodium-calcium exchange to fail, leading to an intracellular accumulation of
sodium and calcium and diffusion of potassium out of the cell. Sodium and water then
can enter the cell freely and cellular swelling results. With continued hypoxia, the entire
cell becomes markedly swollen, with increased concentrations of sodium, water, and
chloride and decreased concentrations of potassium.

11. Syndrome of inappropriate ADH (SIADH)

a. Syndrome of Inappropriate ADH Secretion. ADH is secreted in absence of
hypovolemia or hyperosmolality. Decreased urine formation and/or compulsive water
drinking may occur.
i. ADH makes you retain water and decreases urine output
ii. Inappropriate amount means too much ADH is being secreted and fluid is
being retained
b. Clinical conditions associated with stress result in SIADH: fear, pain, acute infection,
brain trauma, surgery, drugs, and ADH-secreting tumor cells (lungs, pancreas)
c. Clinical manifestation
 i. Acute SIADH: cerebral edema, w/confusion and convulsion
ii. Chronic SIADH: weakness, nausea, muscle twitching, headache, and weight
gain
d. withholding fluid for 24 hours is an effective treatment if there are no convulsions

12. Aldosterone, ADH, & natriuretic peptides as mechanisms of Na control

a. Aldosterone: Triggered by decreased Na+ levels, increased K+ levels, and decreased
renal perfusion. The release of aldosterone increases Na+ reabsorption and K+
secretion in the urine.
b. ADH: Released from the pituitary gland when triggered from ↑ Na+, ↓ water, ↓ BP,
↓ circulating blood volume. ADH increases water reabsorption.
c. Natriuretic peptides: 3 types - Atrial natriuretic peptide (ANP), brain natriuretic
peptide (BNP), urodilatin. Natriuretic peptides decrease BP, allowing for sodium/water
excretion. They’re natural antagonists of the renin-angiotensin-aldosterone system.

13. SIADH (Syndrome of inappropriate ADH) and the effects on fluid/electrolyte balance
a. SIADH (please see #11)
b. SIADH’s effects on fluid/electrolyte balance: SIADH not cause by excess water intake
but by decreased renal excretion of water. Contributes to excess water, thus
hyponatremia occurs.

14. Na & K and repolarization and resting membrane potential (p. 32-33, Chapter 1)
a. This picture may be helpful: http://hyperphysics.phy-
astr.gsu.edu/hbase/biology/imgbio/actpot4.gif
b. Membrane potential steps:
i. Resting membrane potential (RMP): All cells are electrically polarized; inside
of the cell more negatively charged than the outside. The difference in charge
(voltage) is the resting membrane potential (Approx. -70 to -85 millivolts [mV]).
ECF: High [Na+] (sodium concentration) OUTSIDE cell. ICF: High [K+] INSIDE
cell.
1. Concentration difference is maintained by the Sodium-Potassium
(Na+-K+) pump: Pump transports Na+ OUT of cell and K+ INTO cell.
(At RMP, always an excess of anions inside of cell, which creates the
negative charge)
ii. Action Potential: Cell’s response to electrochemical stimuli. A stimulus that
exceeds the membrane threshold value causes a rapid change in the resting
membrane potential ⇒ leads to action potential
1. Resting cell stimulated through voltage-regulated channels
2. Cell membranes become more permeable to SODIUM
3. Depolarization:
a. Net movement of sodium INTO cell
b. Membrane potential decreases (“moves forward”) from a
 negative charge (mV) to zero
c. Depolarized cell is more positively charged; its polarity is
“neutralized”
4. Threshold potential: The critical value (Approx depolarized at +15 to
+20 mV) that must be reach in order to generate an action potential.
a. Threshold is reached, Sodium gates open, Na+ rushes INTO
cell and ↑ positivity of charge
b. Cell continues to depolarize (increase charge to about +30 to
+40 mV)
5. Repolarization: Negative polarity charge gets reestablished.
a. Voltage-gated-sodium channels close, membrane permeability
↓ Na+, but ↑ K+
b. Na+-K+ Pump restores resting potential
c. Absolute Refractory period: During most of action potential, plasma membrane
cannot respond to additional stimulus (only one action potential wave at a time).
related to changes in permeability to sodium
d. Relative Refractory period: Latter phase of action potential. When permeability to
potassium increases and stronger-than normal stimulus can evoke an action potential.
e. Hyperpolarized cell: more NEGATIVE membrane potential (charge difference across
membrane). Less excitable cell (greater charge difference, therefore needs a larger-
than-normal stimulus to reach threshold potential)
f. Hypopolarized cell: more POSITIVE membrane potential. More excitable cell (since it
needs a smaller than normal stimulus to reach its threshold potential)

2 questions/Acid-base balance (Chapter 3):

15. Know interpretation of ABGs

a. Basic interpretation of Arterial Blood Gases (ABGs) involves pH, CO2, HCO3-. pH is a
measure of Acidity/Alkalinity. CO2 is considered an acid and is indicative of
Respiratory conditions. HCO3- is considered a base and is indicative of a Metabolic
issue. Analysis of these levels is used to diagnose conditions of Acidosis/Alkalosis
and distinguish between Respiratory/Metabolic issues.
b. Normal:
i. pH = 7.35 - 7.45
ii. CO2 = 35 - 45 mmHg
iii. HCO3- = 22 -26 mEq/L
c. Procedure:
(Likely to only be confusing in text. Search for videos or find a friend.)
16. Signs and symptoms of:
a. Metabolic acidosis: headache and lethargy are early symptoms. Anorexia, nausea,
vomiting, diarrhea, and abdominal discomfort are common.
b. Metabolic alkalosis: some common symptoms, such as weakness, muscle cramps,
and hyperactive reflexes.
 c. Resp acidosis: initial symptoms include headache, restlessness, blurred vision and
apprehension followed by lethargy, muscle twitching, tremors, convulsions, and coma.
d. Respiratory alkalosis: dizziness, confusion, tingling of extremities (paresthesias),
convulsions, and coma. Deep and rapid respirations (tachypnea) are primary
symptoms.
17. Ratio of Bicarbonate Ion to Carbonic Acid is: 20:1
12 questions/Genetics (Chapters 4 & 5):

18. DNA replication (action of DNA polymerase, transcription) (p. 129)

a. DNA polymerase: Enzyme that travels along single DNA strand, adding correct
nucleotides to the free end of the new strand. It also proofreads by checking if the
bases match, and will correct it if they don’t match, thus enhancing the accuracy of
DNA replication.
b. Transcription: Transcription is the process by which DNA specifies a sequence of
mRNA. A specific portion of DNA is “transcribed” into mRNA. Much of the RNA
sequence is spliced from the mRNA before the mRNA leaves the nucleus. The excised
sequences are called introns, and those that remain to code for proteins are called
exons.
c. Basic steps: DNA Replication (DNA polymerase) → Transcription (formation of mRNA
strand by replicating 1 DNA strand) → Translation (Process of “translating” mRNA into
proteins. Involves tRNA, Ribosomes, codons, amino acid formation, proteins)

19. Chromosome disorders

a. Nondisjunction:
i. Usually the cause of aneuploidy
ii. Failure of homologous chromosomes or sister chromatids to separate normally
during meiosis or mitosis.

b. Aneuploidy: Somatic cells that do not have a multiple of 23 chromosomes are

aneuploid. Aneuploidy is usually the result of nondisjunction.
i. Monosomy is a type of aneuploidy in which only one chromosome is present
instead of the typical pair of sister chromatids.
ii. Trisomy is a type of aneuploidy in which one chromosome is present in three
copies in somatic cells. A partial trisomy is one in which only part of a
chromosome is present in three copies.
iii. In general, monosomies cause more severe physical defects than do trisomies,
illustrating the principle that the loss of chromosome material has more severe
consequences than the duplication of chromosome material.
iv. Most aneuploidies of the sex chromosomes have less severe consequences
than those of the autosomes.
v. The most commonly observed sex chromosome aneuploidies are the 47,XXX
karyotype, 45,X karyotype (Turner syndrome), 47,XXY karyotype (Klinefelter
 syndrome), and 47,XYY karyotype.

c. Polyploidy: a condition in which a euploid cell has some multiple of the normal
number of chromosomes. Humans have been observed to have triploidy (three copies
of each chromosome) and tetraploidy (four copies of each chromosome); both
conditions are lethal.

d. Translocation: simultaneous breaks in two chromosomes from different pairs

(nonhomologous chromosomes) with exchange of chromosome parts. Segments are
joined in an abnormal arrangement.
i. This is different and not to be confused with inversion. Inversion is 2 breaks
within the SAME single chromosome, and the arms switch to opposite sides of
the centromere.

20. Characteristics of
a. Down syndrome:
i. Best-known example of aneuploidy
1. Trisomy 21
ii. 1:800 live births
iii. Risk increases with maternal age
iv. Manifestations
1. Mentally retarded
2. Low (flat) nasal bridge
3. Epicanthal folds
4. Protruding tongue
5. Poor muscle tone
b. Turner syndrome:
i. Females with one X chromosome
ii. Manifestations
1. Absence of ovaries (sterile)
2. Short stature (~4’7”)
3. Webbing of the neck
4. Edema
5. Underdeveloped breasts; wide nipples
6. High number of aborted fetuses
7. X is usually inherited from mother

c. Klinefelter syndrome:
i. Individuals with at least two Xs and one Y chromosome
ii. Some individuals can be XXXY and XXXXY; the abnormalities will increase
with each X
iii. Manifestations
1. Male appearance
2. Develop female-like breasts
 3. Small testes
4. Sparse body hair
5. Long limbs

d. Fragile X syndrome: X linked disorder with a fragile site on the X chromosome

i. Site on the long arm of the X chromosome
1. A small region of the gene undergoes repeated duplication, resulting in
a longer gene which is susceptible to methylation, a chemical process
that results in inactivation of the FMR1 gene
ii. Associated with mental retardation; Second most common cause of mental
retardation after Down’s
iii. Higher incidence in males because they have only one X chromosome, but can
affect females too

21. Genetic principles of

a. penetrance: the % of individuals with a specific genotype who exhibit the expected
phenotype
b. expressivity: Extent of variation in phenotype for a particular genotype. Ex: polydactyl
fingers or toes

22. Examples of auto recessive, auto dominant diseases

a. Auto recessive diseases
● Phenylketonuria (PKU)
● Tay-Saks Disease
● cystic fibrosis
● sickle cell anemia
b. Auto dominant diseases
● Brugada Syndrome
● von Recklinghausen disease
● Huntington disease

23. Autosomal recessive inheritance (see pg 151-152)

a. What is it: Abnormal allele is recessive and a person must be homozygous for the
abnormal trait to express the disease. Manifested only when both copies of the gene
pair are affected. Both parents may be unaffected but are carriers (both have
heterozygous genotype) of the defective gene.
i. The age of onset is usually early in life. The trait usually appears in the
children, not the parents
ii. Affects the genders equally because it is present on a pair of autosomes
b. Recurrence risk of autosomal recessive trait: When two parents are carriers of an
autosomal recessive disease, the occurrence and recurrence risks for each child are
25%

24. Autosomal dominant form of breast cancer (& which genes are responsible?)
 a. What is it: Abnormal allele is dominant, normal allele is recessive, and the genes
exist on a pair of autosomes
b. Recurrence risk of an autosomal dominant trait: When one parent is affected by an
autosomal dominant disease and the other is normal, the occurrence and recurrence
risks for each child are one half (50%)
i. However, there can be a wide variation in gene penetration and expression (ex.
reduced penetrance, incomplete penetrance, and variable expressivity)
c. Breast Cancer:
i. BRCA 1 (chromosome 17) and BRCA 2 (chromosome 13) genes involved in
autosomal dominant breast cancer. Accounts for about 5% of breast cancers.
50%-80% lifetime risk of developing breast cancer. 20-50% lifetime risk of
developing ovarian cancer.

6 questions/Stress & Disease (Chapter 10):

25. know the response of the adrenal cortex to stress; what does it secrete
a. Under stress, ACTH is released by the anterior pituitary to trigger the activation of the
adrenal cortex in your adrenal glands. Cortisol is, therefore, released by the adrenal
cortex into the blood plasma causing multiple physiological effects (see below #26C &
pg. 343, table 10-4).

26. role of hormones & catecholamines (ACTH, norepinephrine, cortisol)

a. ACTH (= Adrenocorticotropic hormone): From anterior pituitary gland. Stimulates the
cortex of the adrenal gland to release cortisol.
b. Norepinephrine: Regulates blood pressure as primary constrictor of smooth muscle in
all blood vessels. During stress, norepinephrine raises blood pressure by constricting
peripheral vessels: dilates pupils of eyes, increases sweat gland action in the armpits
and palms. Little norepinephrine reaches distal tissues, thus effects of norepinephrine
during stress response primarily elicited from sympathetic NS.
c. Cortisol: The primary role of cortisol is to increase blood glucose levels. One of the
main ways it achieves this is through stimulation of gluconeogenesis. Here, the liver
forms glucose from non-carbohydrate sources (amino acids, fatty acids). Figure 10-2
has a good breakdown (pg. 341)
i. Other roles:
1. Protein metabolism - increase in plasma amino acids
a. anabolic action in the liver
b. catabolic action in muscle tissue, skin, bone, lymph tissue,
adipose tissue
2. Lipids -
a. chronic cortisol promotes lipogenesis (lipid formation) in the
abdomen, trunk, and face
b. can also promote lipolysis (fat breakdown) by increasing
catecholamine and growth hormone effects. occurs in adipose
 tissue and extremities
3. Anti-inflammatory effects - can be used as drug therapy (high doses)
to suppress the inflammatory response
a. cortisol stimulates the activity of Th2 cells (T-helper 2) which
leads to the anti-inflammatory response
i. anti-inflammatory response leads to decreased:
lymphocytes, eosinophils, monocytes/macrophages,
kinins, prostaglandins, and histamines
4. Immunosuppression - cortisol can also lead to immunosuppression
a. cortisol, in collaboration with epinephrine, suppress the activity
of Th1 cells (T-helper 1), leading to the immunosuppressed
stage and also the proinflammatory response. (figure 10-4, page
346)

27. Know the three stages of the General Adaptation Syndrome (GAS) and the
pathophysiological response in each and the role of the HPA axis.
a. What is GAS?: Term used to describe the body’s short-term and long-term reaction to
stress.
b. Stage 1 + pathophys response: The Alarm Stage: In which the central nervous system
(CNS) is aroused and the body’s defenses are mobilized (i.e., flight or fight)
c. Stage 2 + pathophys response: The Stage of Resistance or Adaptation: During which
mobilization contributes to flight or fight.
d. Stage 3 + pathophys response: The Stage of Exhaustion: In which continuous stress
causes the progressive breakdown of compensatory mechanisms (acquired
adaptations) and homeostasis. The stage of exhaustion, Selye believed, marked the
onset of certain diseases he called diseases of adaptation.
e. What is an HPA Axis (Hypothalamic-pituitary-adrenal (HPA) Axis) (p. 338):
An endocrine system including interactions among the hypothalamus, pituitary gland,
and adrenal gland. Nonspecific physiologic response identified that consists of
interaction among the sympathetic branch of the autonomic nervous system (ANS)
and other neural signals that activate the endocrine system.
i. Role of HPA Axis: May produce indirect effects on the CNS that modulate
immune responses.

Short Answer questions

1. Be able to describe the 4 causes of edema and explain each mechanism (8 points)
a. Edema: the excessive accumulation of fluid within the interstitial spaces. It is a
problem of fluid distribution and does not necessarily indicate a fluid excess.
b. (See Figure on page 100)
c. Cause 1: Increased capillary hydrostatic pressure
i. Explain: Otherwise known as an increase in blood pressure, it can be due to
venous obstruction, salt and water retention, or heart failure. Alone or in
conjunction with increased sodium or H2O renal retention can lead to edema
d. Cause 2: Decreased plasma oncotic pressure
i. Explain: This can occur either due to decreased production of plasma proteins
(cirrhosis, malnutrition) or increased capillary permeability (burns, allergic
inflammatory reactions) that also result in a loss of plasma proteins.
e. Cause 3: Increased capillary membrane permeability
i. Explain: This results in the loss of plasma proteins leading to decreased
capillary oncotic pressure. The loss of plasma proteins concurrently increases
tissue oncotic pressure (which itself can lead to edema) and decreases the
transport of capillary filtered protein (leading to lymph obstruction).
f. Cause 4: Lymphatic Obstruction
i. Explain: This results in the decreased absorption of interstitial fluid, leading to
edema. Lymphatic system normally absorbs interstitial fluid and small amount of
proteins that pass. When lymphatic channels are blocked (because of infection
 or tumor) or are surgically removed, proteins and fluid accumulate in the
interstitial space ⇒ \t lymphedema.

2. Be able to describe the clinical manifestations (signs: of hypercalcemia (6 points)

a. Hypocalcemia Signs: http://www.youtube.com/watch?v=kvmwsTU0InQ
i. Chvostek sign (cheek twitch) and Trousseau sign (holding chopsticks). (pg
112): Chvostek sign is elicited by tapping on the facial nerve just below the
temple. A positive sign is a twitch of the nose or lip
ii. Trousseau sign is contraction of the[hand and fingers when the arterial blood
flow in the arm is occluded for 5 minutes
iii. Prolonged QT interval in ECG (p.112)
b. Hypocalcemia Symptoms: convulsions and tetany, cramps, confusion
c. Hypercalcemia Signs: Kidney stones, Constipation (sign or symptom?), Bone
Fractures, anorexia, and shortened QT segment & depressed widened T waves in
ECG (p.113)
d. Hypercalcemia Symptoms: fatigue, weakness, lethargy (sign or symptom?), nausea,
and constipation are common.
assd
Case Studies
Given a case study with lab values, be able to describe and interpret fluid and electrolyte findings
AND ABG findings (metabolic/respiratory; acidosis/alkalosis; compensated/uncompensated or
partially compensated) (3 cases, 10, 10, and 6 points)

How to Master ABG's

For reference:
Acidic←------------------------------I------------------------------------>Basic
(Acidosis) 7.40 (Alkalosis)

Normal Ranges:
PH → 7.35---7.45
PaCO2→ 45---35 (Respiratory)
HCO3→ 22--26 (Metabolic)

Examples:

1. PH= 7.55
PaCO2= 20
HCO3=19

ACID NORMAL BASE

HCO3=19 PH =7.55

PaCO2=20

We know PH (7.55) is Alkalosis because it falls above the normal range of 7.35 and 7.45 (see chart
above).
CO2 is Respiratory because it falls below the Normal range of 45 and 35. Since both PH and CO2
are on the Base side, we would say, it is Respiratory Alkalosis.
HCO3 is on the Acid side because it is lower than the normal range of 22 to 26 (see chart above). So,
it Partially Compensate the PH and CO2.

The correct answer is Partially Compensated Respiratory Alkalosis.

For reference:
Acidic←------------------------------I------------------------------------>Basic
(Acidosis) 7.40 (Alkalosis)

Normal Ranges:
PH → 7.35---7.45
PaCO2→ 45---35 (Respiratory)
HCO3→ 22--26 (Metabolic)

2. PH= 7.54
PaCO2= 24
HCO3=25

ACID NORMAL BASE

HCO3=25 PH =7.54

PaCO2=24

Since we know that PH and CO2 falls under Base (see chart above) and CO3 is within the normal
range the answer will be Uncompensated Respiratory Alkalosis.

For reference:
Acidic←------------------------------I------------------------------------>Basic
(Acidosis) 7.40 (Alkalosis)
Normal Ranges:
PH → 7.35---7.45
PaCO2→ 45---35 (Respiratory)
HCO3→ 22--26 (Metabolic)

3. PH= 7.15
PaCO2=46
HCO3=34

ACID NORMAL BASE

PH =7.15 HCO3=34

PaCO2=46

In this scenario, PH and CO2 are on the acid side. This becomes Respiratory Acidosis. Remember:
CO2 is Respiratory and if it is under the acid side with the PH it is Respiratory Acidosis! Since the
CO3 is on the Base side this example becomes Partially Compensated Respiratory Acidosis.

For reference:
Acidic←------------------------------I------------------------------------>Basic
(Acidosis) 7.40 (Alkalosis)

Normal Ranges:
PH → 7.35---7.45
PaCO2→ 45---35 (Respiratory)
HCO3→ 22--26 (Metabolic)

4. PH= 7.33
PaCO2=22
HCO3=21

ACID NORMAL BASE

PH =7.33 PaCO2=22
HCO3=21

In this scenario CO3 and PH are on the Acid side and with CO2 on the Base side. We know that CO3
is Metabolic and PH is acidosis. Since CO2 is partially compensating PH and Co3, the answer is
Partially Compensated Metabolic Acidosis.

For reference:
Acidic←------------------------------I------------------------------------>Basic
(Acidosis) 7.40 (Alkalosis)

Normal Ranges:
PH → 7.35---7.45
PaCO2→ 45---35 (Respiratory)
HCO3→ 22--26 (Metabolic)

5. PH= 7.17
PaCO2=35
HCO3=12

ACID NORMAL BASE

PH =7.17 PaCO2=35

HCO3=12

In this example we have a PH of 7.17 which is below the normal range and thus, acidic. We have
CO3 which is also acidic at 12 and CO2 within normal range. Since there is nothing to compensate
PH and CO3 on the acidic side, the answer will be Uncompensated Metabolic Acidosis.

This may also help you with future examples:

PH and CO2 on Base side= Respiratory Alkalosis

PH and CO2 on Acid side= Respiratory Acidosis
PH and CO3 on Base side= Metabolic Alkalosis
PH and CO3 on Acid side= Metabolic Acidosis

To figure out whether or not it is uncompensated/compensated/partially compensated look at

the loner ABG (i.e., either CO2 or CO3).
PH+CO2 on Base side and CO3 on Acid side= Partially Compensated Respiratory Alkalosis
PH+CO2 on Acid Side and CO3 on Base side= Partially Compensated Respiratory Acidosis
PH+CO3 on Base Side and CO2 on Acid side= Partially Compensated Metabolic Alkalosis
PH+CO3 on Acid side and CO2 on Base side= Partially Compensated Metabolic Acidosis

PH+CO3 on Acid side and CO2 in Normal range= Uncompensated Metabolic Acidosis
PH in normal range but slightly leaning towards Base***** + CO3 on Base and CO2 on Acid=
Compensated Metabolic Alkalosis
PH in normal rage but slightly leaning towards Acid + CO3 on Acid and CO2 on Base side=
Compensated Metabolic Acidosis.

*****A PH of 7.40 would be the midpoint. So if an example is given where you had a PH
between the normal range (7.35 to 7.45), a CO2 either in base or acid range, and a CO3 in
either base or acid range based on your PH you would determine if it is closer to acid or base.

For example, a PH of 7.36 is closer to acid and a PH of 7.44 is closer to base. Based on that, you
would say whether it is “respiratory or metabolic.”