Nancy Caroline’s Emergency Care in the Streets, Ninth Edition

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Lecture Outlines

Chapter 9
Pathophysiology

Unit Summary
After students complete this chapter, they will have an understanding of cellular changes in response to
stressors. The understanding of what happens when the cellular system can no longer maintain
homeostasis is a key component of patient evaluation and treatment.

National EMS Education Standard Competencies

Pathophysiology
Integrates comprehensive knowledge of pathophysiology of major human systems.

Knowledge Objectives
1. Define pathophysiology, including its role in diagnosing and treating disease. (p 488)
2. Compare atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia as means of cellular
adaptation. (p 488)
3. List factors that can affect or upset homeostasis. (pp 489–490)
4. Explain the causes, clinical manifestations, assessment, and management of edema. (pp 490–491)
5. Discuss types of fluid deficits and potential resulting complications. (p 491)
6. Explain the physiologic consequences of electrolyte imbalances in sodium, potassium, calcium,
phosphate, and magnesium. (pp 491–494)
7. Compare respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis.
(pp 495–498)
8. Outline how cellular injury occurs in patients with hypoxia, chemical exposures, infection
(sepsis), immunologic exposures (hypersensitivity reactions), inflammatory conditions, genetic
disorders, nutritional imbalances, physical damage (mechanical injury), and other harmful
exposures, such as extremes of hot and cold. (pp 498–503)
9. Examine the concept of apoptosis. (p 503)
10. Define perfusion, including the physiologic consequences of hypoperfusion. (pp 504–505)
11. Analyze the mechanisms by which the body compensates for hypoperfusion. (pp 504–505)
12. Discuss the causes of central and peripheral shock, including cardiogenic, obstructive,
hypovolemic, and distributive shock. (pp 505–508)
13. Explain how to manage a patient in shock. (pp 508–509)
14. Describe multiple organ dysfunction syndrome. (pp 509–510)
15. Examine the body’s three defense mechanisms against pathogens: anatomic barriers, the immune
response, and the inflammatory response. (pp 510–523)
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16. Explain how plasma protein systems—the complement system, the coagulation (clotting) system,
and the kinin system—modulate the inflammatory response. (pp 519–520)
17. Compare wound healing by primary intention with wound healing by secondary intention. (pp
521–523)
18. Outline each of the four types of hypersensitivity reactions and mechanisms for immunologic
injury. (pp 524–526)
19. List several autoimmune reactions. (pp 526–527)
20. Compare inherited and acquired immunodeficiencies. (pp 527–529)
21. Analyze the controllable and uncontrollable risk factors that intersect to cause disease. (pp 529–
530)
22. Outline how incidence, prevalence, morbidity, and mortality data are used to analyze disease risk.
(p 530)
23. Recognize autosomal dominant and autosomal recessive patterns of inheritance. (pp 530–532)
24. Analyze risk factors for cancer and cardiovascular disease. (pp 533–537)
25. Describe how hematologic disorders occur. (pp 534–535)
26. Name common renal, gastrointestinal, and neuromuscular disorders. (pp 537–540)
27. List the stages of the general adaptation syndrome and explore the relationship between stress and
disease. (pp 541–544)

Skills Objectives
There are no skills objectives for this chapter.

Readings and Preparation

Review all instructional materials including Chapter 9 of Nancy Caroline’s Emergency Care in the
Streets, Ninth Edition, and all related presentation support materials.

Support Materials
 Lecture PowerPoint presentation
 Case Study PowerPoint presentation
 Human body diagram and cellular structure diagram
- Have several copies for each student, as they can serve as a template for many activities and
assessments.
 Pathophysiology: A Practical Approach, Fourth Edition, ISBN: 9781284205435

Enhancements
Direct students to visit Navigate.

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Content connections: Chapter 8, Anatomy and Physiology, has a direct correlation to this chapter. The
assessment of every patient depends on the student’s thorough understanding of anatomy and physiology.
Cultural considerations: Some diseases occur more often in men, and others occur more often in
women. Diseases such as lung cancer, gout, and Parkinson disease are more prevalent in men. Women are
more likely to have diseases such as osteoporosis, rheumatoid arthritis, and breast cancer. Some diseases
present differently in women compared with men. For example, the hormones found in a premenopausal
woman have been shown to have a protective effect in major head trauma and certain cardiac conditions.
Studies are under way to investigate this finding, which could lead to the possibility of administering
female sex hormones to male cardiac arrest patients to improve survival. Finally, genetic disorders are
related to a person’s sex when a defective gene is located on a sex chromosome. Most sex-linked
disorders are X linked. X-linked disorders may be either recessive or dominant.

Teaching Tips
 Images are integral to the retention of material. Prepare them ahead of time, and consider
incorporating web links or videos to enhance student learning.
 Choosing a variety of approaches, including charts, interactive exercises, and group- and self-
assessments, will allow students to organize the new information and identify areas needing more
review. Including multiple activities with visual components will reduce learning time and
increase retention. See the “Student presentation” and “Group activities” sections for suggestions.
This chapter is particularly visually friendly, and with instructor guidance, students can engage in
creative, fun learning.

Unit Activities
Writing activities: Using the systems researched in the “Group activities” section, or selecting another
system, structure, or organ, have each student or group of students write one or two paragraphs on an
illness and an injury that could directly affect the particular organ/structure. What would they expect to
see? Open up the presentations to class discussion if time allows.
Student presentations: Ask students to present their writing assignment to the class, requiring them to
also prepare a one-page self-assessment to be distributed with the presentation.
Group activities: Organize the class into groups. Assign each group to explain one of the following
imbalances: sodium, potassium, calcium, phosphate, or magnesium.
Alternative: After organizing the class into small groups, assign each group a common genetic disorder
encountered in the prehospital setting. Ask each group to prepare a short PowerPoint presentation
containing the following information:
 Description of the disorder
 Signs and symptoms
 Treatment
Visual thinking: Assign a cellular structure to each group with instructions to create a presentation for
the whole class on that system. Each group should be given the same guidelines and questions that must
be answered within the presentation. Questions to consider include:
 What is the location of the structure?
 How does each structure work independently?

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 How does each structure interact with the other parts of this system?
 What other systems interact with this structure?

Pre-Lecture
You are the Paramedic
“You are the Paramedic” is a progressive case study that encourages critical-thinking skills.
Instructor Directions
 Direct students to read the “You are the Paramedic” scenario found throughout Chapter 9
 You may wish to assign students to a partner or a group. Direct them to review the discussion
questions at the end of the scenario and prepare a response to each question. Facilitate a class
dialogue centered on the discussion questions and the Patient Care Report.
 You may also use this as an individual activity and ask students to turn in their comments on a
separate piece of paper.

Lecture

I. Introduction
A. The human body is made up of cells, tissues, and organs.
1. Biology is the study of living organisms with regard to their origin, growth, structure, behavior,
and reproduction.
B. Pathophysiology
1. Study of the physiology of altered functioning in the presence of disease
2. Derived from Greek words
a. Pathos: Suffering
b. Physis: Form
3. When the structure and function in cells, tissues, and organs break down in response to stressors
and the body can no longer maintain homeostasis, disease may result.
4. To understand disease processes, you must understand the ways disease alters the structure and
function of cells.

II. Adaptations in Cells and Tissues

A. When exposed to adverse conditions, cells undergo an adaptation process to attempt to
protect themselves from injury.
1. Change can be permanent or temporary.
2. Atrophy
a. Decrease in cell size due to a loss of subcellular components
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b. The actual number of cells remains unchanged.
c. Decreased size represents an attempt to cope with a new steady state with less-than-favorable
conditions or a lack of use.
3. Hypertrophy
a. Increase in the size of the cells due to synthesis of more subcellular components
4. Hyperplasia
a. Increase in the actual number of cells in an organ or tissue
5. Dysplasia
a. Alteration in the size, shape, and organization of cells
b. Most often found in epithelial cells with irregular, atypical changes
6. Metaplasia
a. Reversible, cellular adaptation in which one adult cell type is replaced by another

III. Disturbances in Fluid Balance

A. The human body is composed primarily of water.
1. All biochemical reactions taking place within the body are occurring in an aqueous environment.
a. Changes in fluid and electrolyte balance that disrupt homeostasis can either cause or
exacerbate various disease processes.
2. Homeostasis can be upset in a number of ways such as by excessive output or input of fluids:
a. Profuse sweating
b. Excessive salt intake
c. Dehydration
i. A person deprived of water for 3 days or more may die.
3. The degree of fluid imbalance required to compromise homeostasis and cause illness depends on
the patient’s:
a. Size
b. Age
c. Any underlying medical conditions
i. In healthy adults, loss of more than 30% of total body fluid is required.
ii. In a small child, a loss of only 10% to 15% of total body fluid could produce symptoms.
iii. Fluid therapy is a fundamental step in resuscitation.
B. Edema
1. Edema is an excessive amount of fluid in the interstitial space.
a. May have several causes:
i. Increased capillary hydrostatic pressure from:
(a) Arteriolar dilation
(b) Venous obstruction
(c) Increased vascular volume

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(d) Increased level of adrenocortical hormones
(e) Premenstrual sodium retention
(f) Pregnancy
(g) Environmental heat stress
(h) Effects of gravity from prolonged standing
ii. Decreased colloidal osmotic pressure in the capillaries from:
(a) Decreased production of plasma proteins
(b) Increased loss of plasma proteins
iii. Lymphatic vessel obstruction due to infection, lymphatic disease, or removal of
lymphatic structures (eg, lymph nodes)
b. Severe edema may be caused by long-standing lymphatic obstruction.
i. Peripheral edema (ankles and feet) is the most common form.
ii. Sacral edema may occur in bedridden patients.
iii. Ascites: Abnormal accumulation of fluid in the peritoneal cavity; also a type of edema
c. Clinical manifestations
i. May be local or generalized
ii. Pulmonary edema: Patients with cardiac disease or following submersion, narcotic
overdose, or high-altitude pulmonary edema (HAPE)
d. Assessment and management
i. Must perform an in-depth assessment including:
(a) Auscultation of breath sounds
(b) Evaluation for pedal or sacral edema and jugular venous distention
(c) Electrocardiogram (ECG) and vital signs
ii. Determine a patient’s medical history and current and past medications.
iii. Treatment dictated by patient’s chief complaint, presenting problem, and may include:
(a) Continuous positive airway pressure (CPAP)
(b) Supplemental oxygen
(c) Positional therapy
(d) Nitrates
(e) Diuretics
C. Isotonic fluid deficit
1. Decrease in extracellular fluid with proportionate losses of sodium and water
a. Most common form of fluid loss
b. Common causes of such deficits include:
i. Vomiting
ii. Diarrhea
iii. Loss of plasma or whole blood (eg, burns, hemorrhage)
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iv. Use of loop diuretics, fever, decreased oral fluid intake
v. Excessive sweating
c. Excessive sweating or combining increased physical exertion with other comorbidities may
complicate the fluid loss and cause additional problems.
2. Isotonic fluid excess: Proportionate increase in both sodium and water in the extracellular fluid
compartment
a. Causes include heart failure, cirrhosis, renal failure, steroids, and excessive sodium intake.
b. Manifestations of conditions depend on serum sodium level.
3. When dehydration exists, orthostatic hypotension and decreased urine output (oliguria) are
common.
4. When sodium level is very high, the patient is at risk for delirium and coma.

IV. Electrolyte Imbalances

A. Sodium
1. An element essential to the human body that is found primarily in the blood and fluid outside the
cells
2. Functions
a. Regulates fluid balance, total fluid volume, and blood pressure by controlling the movement
of water across cellular membranes
b. Facilitates muscle contraction and nerve impulse transmission
3. Abnormal sodium levels may result in nausea, weakness, confusion, and seizures.
a. Normal serum sodium levels are 136 to 142 mEq/L.
b. Hypertonic fluid deficit: Caused by excess body water loss without a proportionate sodium
loss
i. Results in hypernatremia (serum sodium level greater than 143 mEq/L)
c. Hypotonic fluid deficit: Caused by sodium loss in the body without a proportionate loss of
water (water excess)
i. Results in hyponatremia (serum sodium level less than or equal to 135 mEq/L)
4. Causes of hyponatremia include heart failure, cirrhosis, or renal failure, and a normal fluid
volume with hyponatremia can be caused by syndrome of inappropriate antidiuretic hormone
(SIADH).
a. Some patients experience fatigue, loss of appetite, nausea, muscle cramps, weakness,
abdominal discomfort or cramps, headache, confusion, seizures, and decreased BP.
b. Clinical findings typically depend not only on the absolute sodium level but also on when the
abnormality developed.
i. People who develop the abnormality acutely have more symptoms than people who
develop symptoms over a period of days.
B. Potassium

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1. The major intracellular cation is crucial to many cellular functions, such as:
a. Neuromuscular control
b. Regulation of the three types of muscles
c. Regulation of acid–base balance
d. Facilitation of intracellular enzyme reactions
e. Maintenance of intracellular osmolarity
i. Normal serum potassium levels are 3.5 to 5.0 mEq/L.
2. Hypokalemia: Decreased serum potassium level
a. Common causes include decreased potassium intake and absorption, potassium shifts into
cells, renal potassium losses, and extrarenal potassium losses.
b. Frequent symptoms include muscle weakness, fatigue, and muscle cramps.
c. Ascending paralysis, hyporeflexia, and tetany may occur.
d. Can be treated with IV potassium supplementation in the hospital setting
3. Hyperkalemia: Elevated serum potassium level
a. Common causes include:
i. Decreased excretion (from renal failure or medications)
ii. Shifts of potassium from within the cell (such as burns, crush injuries, metabolic acidosis,
and insulin deficiency)
iii. Excessive dietary intake of potassium
b. Interferes with normal neuromuscular function
i. May lead to fatigue, nausea, muscle weakness, abnormal sensations (paresthesias), and,
rarely, ascending paralysis
ii. ECG changes and cardiac dysrhythmias typically precede these signs.
C. Calcium
1. Majority (98%) is found in bone and teeth.
2. Provides strength and stability for the collagen and ground substance forming the matrix of the
skeletal system
3. Enters the body through the gastrointestinal tract
4. Absorbed from the intestine in a process that depends on the presence of vitamin D
5. Calcium is stored in bone tissue and ultimately excreted by the kidney.
6. Normal serum calcium level is 8.2 to 10.2 mg/dL.
7. Hypocalcemia: Decreased serum calcium level
a. Caused by:
i. Decreased intake or absorption (as in malabsorption and vitamin D deficit)
ii. Increased loss (such as in alcoholism and diuretic therapy)
iii. Endocrine disease (such as hypoparathyroidism)
iv. Sepsis
b. Signs and symptoms include:
i. Skeletal muscle spasm causing cramps and tetany
ii. Laryngospasm
iii. Seizures

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iv. Abnormal sensations (paresthesias) of the lips and extremities
c. Cardiac dysrhythmias may be observed on the ECG.
8. Hypercalcemia: Increased serum calcium level
a. Caused by:
i. Increased intake or absorption (such as with excess antacid ingestion)
ii. Endocrine disorders (such as primary hyperparathyroidism and adrenal insufficiency)
iii. Neoplasms (cancers)
iv. Miscellaneous causes (such as diuretics and sarcoidosis)
b. Signs and symptoms include:
i. Fatigue
ii. Weakness
iii. Nausea
iv. Constipation
v. Frequent urination (polyuria)
c. Treatment depends on addressing the underlying cause.
9. Refer to Figure 9-3.
D. Phosphate
1. Intracellular anion essential to many functions
2. Phosphate levels are regulated by the same mechanisms that regulate calcium.
3. Hypophosphatemia: Decrease in serum phosphate levels
a. Caused by:
i. Decreased supply or absorption, as can occur in starvation, malabsorption, or blocked
absorption (such as with aluminum-containing antacids)
ii. Excessive loss of phosphate in patients with hyperparathyroidism, hyperthyroidism, or
alcoholism
iii. Intracellular shift of phosphorus (such as after administering glucose, anabolic steroids,
or oral contraceptives, or in patients with respiratory alkalosis or salicylate poisoning)
iv. Electrolyte abnormalities, such as hypercalcemia and hypomagnesemia
v. Abnormal loss of nutrients followed by inadequate replenishment, as can occur in
patients with diabetic ketoacidosis or chronic alcoholism
b. Signs and symptoms include:
i. Dysrhythmias
ii. Hypotension
iii. Muscle weakness
iv. Altered mental status
v. Breakdown of muscle fibers (rhabdomyolysis)
vi. Loss of appetite
vii. Tremors
viii.Paresthesias
ix. Seizures, coma, acute blood disorders, and increased susceptibility to infection
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c. Treatment involves oral replenishment in mild to moderate cases and IV phosphate
replacement in severe cases.
4. Hyperphosphatemia: Increase in serum phosphate levels
a. Caused by:
i. Massive loading of phosphate into the extracellular fluid
(a) Excessive use of vitamin D, laxatives, or enemas containing phosphate
(b) IV phosphate supplements
(c) Chemotherapy
(d) Metabolic acidosis
ii. Decreased excretion into the urine (such as in renal failure and hypoparathyroidism, and
with excessive administration of growth hormone
(a) Results in acromegaly
b. Signs and symptoms include:
i. Tremor
ii. Paresthesia
iii. Hyperreflexia (overactive reflexes)
iv. Confusion
v. Seizures
vi. Muscle weakness
vii. Decreased mental status
viii.Coma
ix. Hypotension
x. Heart failure
xi. Prolonged QT interval
c. The normal range for serum phosphate is 2.3 to 4.7 mg/dL.
E. Magnesium
1. Second most abundant intracellular cation
a. Normal range of serum magnesium is 1.3 to 2.1 mEq/L.
2. Hypomagnesemia: Decreased serum magnesium level
a. Caused by:
i. Diminished magnesium absorption or intake (as occurs in alcohol use disorder, decreased
dietary consumption, malabsorption, or malnutrition)
ii. Increased renal loss of magnesium (related to thiazide diuretic use, chronic kidney
disease, primary aldosteronism, hypercalcemia, or genetic diseases)
iii. Increased GI loss of magnesium (related to diarrhea, vomiting, celiac disease,
inflammatory bowel disease, or proton pump inhibitor use)
iv. Miscellaneous causes, such as insulin administration and pancreatitis
b. Symptoms include:
i. Weakness
ii. Muscle cramps
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iii. Neuromuscular and central nervous system (CNS) hyperirritability, with tremors and
jerking
iv. Insomnia
v. Personality changes
vi. Hypertension
vii. Tachycardia
viii.Ventricular dysrhythmias
ix. Confusion and disorientation
3. Hypermagnesemia: Increased serum magnesium level
a. Results from kidney insufficiency and the inability to excrete the amount of magnesium taken
in
b. Symptoms include:
i. Muscle weakness
ii. Decreased deep tendon reflexes
iii. Altered mental status
iv. Cardiac dysrhythmias
v. Respiratory muscle paralysis (possible)
vi. Cardiac arrest (possible)

V. Disturbances of Acid–Base Balance

A. pH
1. Represents the concentration of hydrogen ions (H+) in a solution
a. A measure of the acidity or alkalinity of a solution
b. There is an inverse relationship between pH and H+ ion concentration: the lower the pH, the
higher the acidity.
B. Disturbances of acid–base balance
1. Acid and bases neutralize each other and must remain in balance.
a. Main patient issues you encounter as a paramedic will have this component.
b. Acidosis is an increase in extracellular H+ ions.
c. Alkalosis is a decrease in extracellular H+ ions.
2. Disturbances of acid–base balance are associated with disturbances in potassium balance.
a. Kidney transport system moves H+ and K+ in opposite directions.
i. Acidosis: Excretes H+ and resorbs K+.
ii. Alkalosis: Excretes K+ and resorbs H+.
3. Calcium ions also shift out of the cell in response to the influx of hydrogen ions.
C. Types of acid-base imbalance
1. Fluctuations in pH due to bicarbonate levels result in metabolic acidosis or alkalosis.
2. Fluctuations in pH due to respiratory disorders result in respiratory acidosis or alkalosis.

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3. When an acid–base disorder is not immediately correctable by the body’s buffering systems, the
body initiates compensatory mechanisms.
4. There are four main clinical presentations:
a. Respiratory acidosis
i. Always related to hypoventilation
ii. Compensatory mechanism is the renal buffer system
iii. Causes include upper airway disease (eg, aspiration, laryngospasm, obstructive sleep
apnea, airway obstruction); pulmonary disease (eg, asthma, chronic obstructive
pulmonary disease [COPD], acute respiratory distress syndrome, pneumonia, pulmonary
edema); miscellaneous causes (eg, muscular dystrophy, multiple sclerosis, obesity
hypoventilation syndrome, closed head injury, chest trauma, respiratory or cardiac arrest)
iv. Hypoventilation can quickly develop a potentially fatal acidosis making it impossible for
the slow reacting renal system to compensate.
v. Signs and symptoms include systemic or cerebral vasodilation (or both); headaches,
light-headedness, restlessness; warm, flushed skin; CNS depression; nausea and
vomiting.
vi. Chronic obstructive pulmonary disease (COPD) creates a respiratory acidosis over time.
b. Respiratory alkalosis
i. Associated with conditions that result in hyperventilation.
ii. Carbon dioxide levels in the blood drop, reducing the level of circulating carbonic acid.
iii. Renal system begins to retain H+ ions to rebalance the depleted acid level.
(a) H+ ions begin to shift from the extracellular fluid compartment to the intracellular
fluid.
iv. Causes of hyperventilation and respiratory alkalosis include medications, CNS
stimulation, pulmonary causes, and miscellaneous causes.
v. Signs and symptoms include light-headedness, carpopedal spasm, paresthesias of the lips,
face, and extremities, chest tightness, palpitations, vertigo, and blurred vision.
c. Metabolic acidosis
i. Any acidosis not related to the respiratory system
ii. Increased breathing rate (tachypnea) is the compensatory mechanism for this condition.
iii. The body attempts to restore acid–base balance by eliminating excess CO 2 through the
respiratory system.
iv. The kidneys attempt to compensate for the acidosis by retaining bicarbonate ions and
eliminating hydrogen ions in the urine.
v. Causes include:
(a) Lactic acidosis caused by anaerobic cellular respiration
(b) Ketoacidosis caused when cells metabolize fatty acids for energy because they are
unable to use glucose
(c) GI losses, which can precipitate metabolic acidosis
(d) Ingestion of some drugs or toxins, leading to metabolic acidosis
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vi. The clinical presentation of metabolic acidosis includes:
(a) Headaches, drowsiness
(b) Loss of appetite
(c) Tachypnea
(d) Nausea and vomiting
(e) Cardiac dysrhythmias
d. Metabolic alkalosis
i. Occurs when there is excessive loss of acid from increased urine output or decreased
gastric acid level in the stomach
ii. Common among chronically ill patients
iii. Several factors associated with upper GI losses can lead to metabolic alkalosis:
(a) Excessive vomiting
(b) Excessive water intake
(c) Nasogastric suctioning
(d) Excessive intake of alkaline substances, such as antacids or similar alkaline
substances
iv. Signs and symptoms include light-headedness, confusion, paresthesias, muscle tremors
and cramps, and possibly cardiac dysrhythmias.

VI. Cellular Injury

A. Overview
1. The manifestations of cellular injury or death depend on:
a. How many cells are damaged
b. Which types of cells are damaged
2. Various causes:
a. Hypoxia, ischemia, chemical injury, infectious injury, immunologic injury, physical damage,
and inflammatory injury
3. Manifestations occur at both the microscopic and functional levels.
a. Common microscopic abnormalities include cell swelling, rupture of cell membranes or
nuclear membranes, and breakdown of nuclear material.
b. Functional disturbances may include inefficient oxygen utilization, intracellular acidosis,
toxic waste accumulation, and derangement of nutrient metabolization.
4. Changes in individual cells often affect the entire organism.
a. Changes can be associated with only minor systemic abnormalities (eg, fever) or the entire
organ system may collapse.
b. Dysfunction in one system inevitably affects other systems.
5. Repair may occur up to a point, with proper treatment.
a. Irreversible injury will lead to cell death.
b. Cell death is followed by necrosis.
6. Refer to Figure 9-5.

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B. Hypoxic injury
1. Common cause of cellular injury
a. Often deadly
b. May result from decreased amounts of oxygen in the air or loss of hemoglobin function, a
decreased number of red blood cells, disease of the respiratory or cardiovascular system, or
loss of cytochromes
2. Cells that are hypoxic for more than a few seconds produce mediators that damage areas near or
far from the initial area of damage in the body.
a. A positive feedback cycle leads to more cell damage and more hypoxia.
3. The earliest and most dangerous mediators are free radicals.
a. Free radicals: Molecules missing one electron in the outer shell
i. Chemical instability causes random attacks on other cells and membranes.
ii. Results in widespread and potentially deadly tissue damage
C. Chemical injury
1. A variety of chemicals, including poisons, lead, carbon monoxide, ethanol, and pharmacologic
agents, may injure and ultimately destroy cells.
2. Common poisons:
a. Cyanide: Induces cell hypoxia by blocking oxidative phosphorylation in the mitochondria
and preventing the metabolism of oxygen
b. Pesticides: Block an enzyme preventing proper transmission of nerve impulses
3. Lead
a. Long-term ingestion leads to brain injury and neurologic dysfunction
b. The ability of lead to substitute for calcium (molecules of lead and calcium are a similar size)
is a common factor in many of its toxic actions.
4. Carbon monoxide
a. Binds to hemoglobin more easily than does oxygen
b. Low levels cause nausea, vomiting, and headache.
c. Higher levels result in death.
5. Ethanol
a. Lower levels, as found in drinking alcohol, cause inebriation.
b. Higher doses result in severe CNS depression, hypoventilation, and cardiovascular collapse.
6. Pharmacologic agents
a. Produce toxic products when metabolized in the body
D. Infectious injury
1. Infectious injury to cells occurs as a result of an invasion of bacteria, fungi, or viruses.
2. Bacteria may cause injury by:
a. Direct action on cells
b. The production of toxins

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3. Viruses often initiate an inflammatory response.
a. Leads to cell damage and patient symptoms
4. Virulence
a. Measures the disease-causing ability of a microorganism
b. Pathogenicity is a function of microorganism’s ability to reproduce and cause disease within
the human body.
c. Growth and survival of bacteria in the body depend on the:
i. Effectiveness of the body’s own defense mechanisms
ii. Bacteria’s ability to resist the mechanisms
d. Newborn infants, older adults, people with diabetes, and people with cancer or other chronic
diseases tend to have weaker immune systems.
5. Bacteria
a. Many possess a capsule that protects them from ingestion and destruction by white blood
cells.
b. Categorized depending on results of Gram staining
i. Gram staining: Suspension of bacteria is stained with a purple dye and then an iodine
solution
(a) Then decolorized with alcohol or another solvent
(b) Then stained with red dye
ii. Bacteria that resist decolorization are called gram-positive bacteria.
iii. Bacteria that accept the counterstain are called gram-negative bacteria.
c. Produce exotoxins or endotoxins that can injure or destroy cells
i. Exotoxins are produced within the cell and released into surrounding tissues or fluids.
(a) Poisonous
(b) Actions vary
(c) Inactive exotoxins are sometimes used for vaccines.
ii. Endotoxins are lipopolysaccharides that are part of the cell walls of gram-negative
bacteria.
(a) Cause inflammation, fever, chills, and malaise
(b) May cause septic shock if present in large amounts
(c) Remain active even after the bacteria are destroyed
d. White blood cells are attracted to the site of cell injury.
i. Release endogenous pyrogens (cause a fever to develop)
e. The body’s most common reaction to the presence of bacteria is inflammation.
f. Some bacteria have the ability to produce hypersensitivity reactions.
i. Bacteremia: Presence of bacteria in the blood
ii. Septicemia: Systematic disease caused by the proliferation of microorganisms in the
blood
6. Viruses
a. Intracellular parasites that take over the metabolic processes of the host cell and use the cell
to help them replicate
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b. Consist of a nucleic acid core of either RNA or DNA
c. Capsid: Layer of protein that protects the virus from phagocytosis
d. Replication occurs inside the host cell.
e. Viruses induce pathology by disrupting the normal metabolic processes, but are protected
from antibiotics by:
i. Living and replicating inside the host cell
ii. Effectively hiding from the medication
f. A symbiotic relationship between a virus and normal cells may be the cause of a persistent
unapparent infection.
E. Immunologic and inflammatory injury
1. Inflammation is a protective response occurring in the presence of cellular injury, including
trauma, infection, and hypoxia.
a. Infection is characterized by an invasion of microorganisms that causes cell or tissue injury
leading to the inflammatory response.
i. Can be triggered by an agent that is physical, chemical, or microbiologic
b. Local effects include dilation (expansion) of blood vessels and increased vascular
permeability.
c. Signs include heat, redness, tenderness, swelling, and pain.
d. Severe systemic effects include temperature elevation and increase in the number of
leukocytes (leukocytosis).
e. Outcome depends on amount of tissue damage:
i. Mild inflammation results in the return of normal tissue.
ii. More severe inflammation results in destroyed tissue that must be repaired.
(a) Scar tissue replaces large areas of tissue destruction.
f. Cellular membranes may be injured when they come in direct contact with the cellular and
chemical components of the immune or inflammatory process.
i. Potassium leaks out of the damaged cell and water flows inward, causing the cell to
swell.
2. Refer to Figure 9-7.
F. Injurious genetic factors
1. Genetic factors that may damage cells include:
a. Chromosomal disorders
b. Premature development of atherosclerosis
c. Obesity (sometimes)
2. An abnormal gene may develop:
a. If the gene mutates during meiosis
i. Affects newly formed fetus
b. By heredity
c. Due to other causes later in life

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3. Examples of diseases with a genetic link include trisomy 21 (Down syndrome) and rheumatoid
arthritis.
G. Injurious nutritional imbalances
1. Good nutrition is required to:
a. Maintain good health
b. Assist the cells in fighting off disease
2. Injurious nutritional imbalances include:
a. Obesity
b. Malnutrition
c. Vitamin excess or deficiency
d. Mineral excess or deficiency
3. These conditions lead to:
a. Alterations in physical growth
b. Mental and intellectual retardation
c. Death
H. Injurious physical agents or conditions
1. Physical agents include heat, cold, and radiation.
a. May cause injury
i. Burns, frostbite, radiation sickness, and tumors
b. Degree of cell injury is determined by the:
i. Strength of the agent
ii. Length of exposure
I. Apoptosis
1. Normal cell death
a. Genetically programmed into the cell as a part of normal development, organogenesis,
immune function, and tissue growth
b. Normal role in aging, early development, menses, lactating breast tissue, thymus involution,
and red blood cell turnover
2. During apoptosis:
a. Cells exhibit characteristic nuclear changes and die in well-defined clusters.
b. Activation of genes that encode for proteins known as caspases essentially leads to cell
suicide.
c. Controlled degradation allows their remnants to be taken up and reused by neighboring cells.
3. Can be prematurely activated by pathologic factors (cell injury)
a. Some forms of heart failure can result in early cell death.
b. Death of hepatocytes (liver cells) in patients with viral hepatitis, yellow fever, and other viral
diseases
c. Inhibition of normal function allows destructive cellular proliferation (cancer and rheumatoid
arthritis).
J. Abnormal cell death

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1. Necrosis: Term for tissue death
a. Result of the morphologic changes that occur following cell death in living tissues
b. Simple necrosis
i. Areas of necrosis where the gross and microscopic tissue and some of the cells are
recognizable
ii. May be caused by acute ischemia, acute toxicity, or direct physical injury
c. Derived necrosis
i. Caseation necrosis: Manifested by the loss of all features of the tissue and cells
ii. Dry gangrene: Results from invasion and putrefaction of necrotic tissue, after the blood
supply is compromised and the tissue undergoes coagulation necrosis
iii. Fat necrosis: Results from the destruction of fat cells, usually by enzymes
iv. Liquefaction necrosis: Results from coagulation necrosis followed by conversion of
tissues into a liquid form and invasion by putrefying bacteria

VII. Hypoperfusion
A. Perfusion is the delivery of oxygen and nutrients and removal of wastes from the cells,
organs, and tissues by the circulatory system.
1. Adequate circulation is dependent upon a pumping heart, intact vascular system, and an
appropriate amount of oxygen-carrying blood.
2. A deficiency in any of these areas will cause problems with perfusion.
B. Hypoperfusion occurs when the level of tissue perfusion decreases below normal.
1. When the body senses tissue hypoperfusion, it sets compensatory mechanisms into motion.
a. Signs of compensated and decompensated (hypotensive) shock appear in Table 9-2.
2. Response to hypoperfusion
a. The body releases catecholamines (epinephrine and norepinephrine), which produce:
i. Increased strength of cardiac contraction (positive inotropy)
ii. Increased pulse rate
iii. Vasoconstriction
iv. Increased systemic vascular resistance
b. The renin-angiotensin-aldosterone system (RAAS) is activated, and antidiuretic hormone is
released from the pituitary gland.
c. Actions trigger salt and water retention as well as peripheral vasoconstriction, thereby
increasing the amount of fluid in the vascular space and improving blood pressure and
cardiac output.
d. Fluid shifts from the interstitial tissues into the vascular compartment.
3. The overall response is to increase the preload, stroke volume, and heart rate to ensure adequate
cardiac output.
a. The result is often an increase in cardiac output and myocardial oxygen demand.
4. Persistence results in a continued increase in myocardial stress.
a. Compensatory mechanisms can no longer keep up with the increased oxygen demand.
i. Myocardial function worsens.
ii. Tissue perfusion decreases, causing impaired cell metabolism.
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iii. Fluid may leak from the blood vessels, causing systemic and pulmonary edema.
iv. Other signs may be present: dyspnea, dusky skin, low blood pressure, oliguria, and
impaired mentation.
5. In times of profound hypotension, blood flow through the capillary membrane decreases and the
hydrostatic push fails.
a. Postcapillary sphincters contract, blocking the outflow of blood from the capillary.
b. This mechanism attempts to increase the flow of plasma across the capillary membrane.
c. The consequent pooling of blood in the capillaries produces mottled skin.
C. Shock is an abnormal state associated with inadequate oxygen and nutrient delivery to
the metabolic apparatus of the cell.
1. Results in impairment of cellular metabolism and ultimately inadequate perfusion of vital organs
a. Prevents the body from properly using oxygen and glucose at the cellular level
i. Cells revert to anaerobic metabolism.
ii. Glucose impairment leads to elevated blood glucose levels as catecholamines and cortisol
are released.
iii. Fat breakdown (lipolysis) with ketone formation may occur.

VIII. Types of Shock

A. Shock occurs due to inadequacy of the central circulation or of the peripheral
circulation.
1. Central shock: Consists of cardiogenic shock and obstructive shock
2. Peripheral shock: Includes hypovolemic shock and distributive shock
B. Central shock
1. Cardiogenic shock
a. Occurs when the heart cannot circulate enough blood to maintain adequate peripheral oxygen
delivery
b. Most common cause is myocardial infarction
2. Obstructive shock
a. Occurs when blood flow becomes blocked in the heart or great vessels
i. Pericardial tamponade: Diastolic filling of the right and left ventricles is impaired due to
significant amounts of fluid in the pericardial sac surrounding the heart.
ii. Decreased ventricular filling associated with pericardial tamponade leads to a decrease in
the cardiac output.
iii. Aortic dissection leads to a false lumen with loss of normal blood flow.
iv. Left atrial tumor may obstruct flow between the atrium and ventricle and decrease
cardiac output.
v. Obstruction of the superior or inferior vena cava decreases cardiac output by decreasing
venous return.
vi. A large pulmonary embolus or a tension pneumothorax may prevent adequate blood flow
to the lungs, resulting in inadequate venous return to the left side of the heart.
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C. Peripheral shock
1. Hypovolemic shock
a. Circulating blood volume is insufficient to deliver adequate oxygen and nutrients to the body.
b. Two types: Exogenous and endogenous
c. External bleeding: Most common type of exogenous hypovolemic shock
d Endogenous shock occurs when the fluid loss is contained within the body.
2. Distributive shock
a. Occurs when there is widespread dilation of the resistance vessels, the capacitance vessels, or
both
i. Circulating blood volume pools in the expanded vascular beds, and tissue perfusion
decreases.
b. Three common types:
i. Anaphylactic shock (anaphylaxis)
(a) Histamine and other vasodilator proteins are released upon exposure to an allergen.
(b) Accompanied by wheezing and urticaria (hives)
(c) Widespread vasodilatation causes fluid to leak out of the blood vessels into the
interstitial spaces.
ii. Septic shock
(a) Result of widespread infection, usually bacterial
(b) If normal immune mechanisms become overwhelmed, the body produces many
substances that cause vasodilation and decreased cardiac output.
(c) If untreated, results in multiple organ dysfunction syndrome and death
iii. Neurogenic shock
(a) Usually results from spinal cord injury
(b) Loss of normal sympathetic nervous system tone and vasodilation
D. Management of shock
1. Most types of shock are characterized by reduced cardiac output, circulatory insufficiency, and
rapid heartbeat.
2. Determining the presence or absence of shock requires the evaluation of the presence and volume
of the peripheral pulses, and assessment of end-organ perfusion and function.
a. The strength of peripheral pulses is related to both stroke volume of the heart and pulse
pressures.
b. Normal skin perfusion is indicated by warm, dry extremities, fingers, and toes.
c. Shock may result in slow, delayed, or prolonged capillary refill time.
3. Mottling, pallor, peripheral or central cyanosis, and delayed capillary refill may signal the
presence of shock.
4. Measuring end-tidal carbon dioxide (ETCO2) may also be useful.
a. Interpret the effectiveness of perfusion based on changes in capnography and capnometry.
b. Decreasing levels of ETCO2 are an early indicator of shock.
c. Low levels of ETCO2, combined with other signs/symptoms of shock such as hypotension and
altered mental status, are ominous clinical findings.
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IX. Multiple Organ Dysfunction Syndrome (MODS)

A. MODS is a progressive condition that occurs in some critically ill patients.
1. Characterized by concurrent failure of two or more organs or organ systems that were initially
unharmed
a. Six organ systems surveyed in diagnosing: Respiratory, hepatic, renal, hematologic,
neurologic, and cardiovascular
b. The disease process often progresses in a cyclical manner, including multiple organ systems
and complicating factors.
c. Overall mortality rate varies widely depending on the underlying etiology and ensuing
diagnosis and treatment.
d. This condition is often reversible, particularly in patients who were healthy before the
physiologic insult occurred.
e. Major cause of death following sepsis, trauma, and burn injuries, with mortality rates as high
as 70%
2. Types include:
a. Primary MODS: Direct result of an insult
b. Secondary MODS: Slower, more progressive organ dysfunction
3. Results when injury or infection triggers a massive systemic immune, inflammatory, and
coagulation response accompanied by endotoxin release
a. Overactivation of the complement system further increases inflammation and cellular
damage.
b. Overactivation of the coagulation system causes uncontrolled coagulation in the venules and
arterioles
c. Bradykinin, a potent vasodilator, is released.
4. Net outcome is maldistribution of systemic and organ blood flow.
5. Typically develops hours to days following resuscitation
6. Signs and symptoms include hypotension, insufficient tissue perfusion, uncontrollable bleeding,
and multisystem organ failure.
a. During 14- to 21-day period, renal and liver failure can develop, along with collapse of the
gastrointestinal and immune systems.
i. Treatment focuses on minimizing the effects of liver damage.
b. Brain, adrenal glands, and heart are affected early on.
i. Hypotension cannot be controlled.
ii. Cardiovascular collapse and death typically occur within days to weeks of the initial
insult.

X. The Body’s Self-Defense Mechanisms

A. The immune system includes all structures and processes associated with the body’s
defense against foreign substances and disease-causing agents.
1. Three lines of defense: Anatomic barriers, the inflammatory response, and the immune response
B. Anatomic barriers

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1. Several decrease the chances of bodily invasion by foreign substances.
a. Skin
b. Hairs in the upper respiratory tract and the lining of the lower respiratory tract
c. Acid in the stomach
C. Immune response
1. Body’s defense reaction to any substance that is recognized as foreign
a. Directed toward invading microbes (bacteria or viruses)
b. Also triggered by foreign bodies and even abnormal cell growths
2. Involves only one type of white blood cells (lymphocytes)
a. Not all microbes can be destroyed.
b. Often succeeds in preventing severe disease following infection
3. The body responds to different kinds of immune challenges in remarkably similar ways.
a. The details depend on the particular challenge, but the basic pattern is the same:
i. The innate response starts first.
ii. The more specific acquired response reinforces the first response.
4. Consider what happens when bacteria enter the body.
a. If the bacteria are not encapsulated, then macrophages immediately ingest the bacteria.
b. If the bacteria are encapsulated, then antibodies must coat the capsule before it can be
ingested by phagocytes.
c. Components of the cell wall then activate the complement system.
d. Some components of the complement system (chemotaxins) attract leukocytes from the
circulation to help fight the infection.
e. The complement cascade ends with the formation of a set of proteins called the membrane
attack complex.
i. These molecules insert themselves into the bacterial membrane, weakening those areas in
the membrane.
ii. Ions and water enter the cell through the weakened areas.
iii. Process leads to lysis of the bacterium.
5. If antibodies to the bacteria are already present in the body, then these antibodies will neutralize
the bacterial toxins.
a. Memory B cells attracted to the infection site will be activated if a recognized antigen is
encountered.
b. If the infection is new to the body, then B cells will be activated.
i. Helper T cells and cytokines are then released, antibodies are produced, and memory B
and T cells are formed.
6. Characteristics of the immune response
a. Native and acquired immunity protect the body from infectious agents and foreign
substances.
b. Natural (native) immunity: Nonspecific cellular and humoral (antibody) response that
operates as the first line of defense against pathogens
i. Associated with the initial inflammatory response
c. Acquired (adaptive) immunity: Highly specific method by which cells respond to an immune
stimulant
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i. Activated when the body is exposed to a foreign substance or disease and produces
antibodies to that invader
ii. Passively acquired immunity is the receipt of preformed antibodies to fight or prevent
infection.
d. Primary (initial) immune response takes place during first exposure to an antigen (foreign
substance).
i. Secondary immune response occurs with reexposure to a foreign substance.
7. Antibody: Binds a specific antigen so the complex can attach itself to specialized immune cells
that destroy the complex or induce a response
a. Immunogen: An antigen capable of generating an immune response
i. Hapten: Substance that normally does not stimulate an immune response but that can be
combined with an antigen and, at a later time, initiate a specific antibody response on its
own
8. Humoral immune response
a. Humoral immunity: B cell lymphocytes produce antibodies (immunoglobulins) that react
with a specific antigen
b. B lymphocytes are born in the bone marrow (descended from stem cells).
i. Clonal selection theory: Each B cell makes antibodies that have only one type of antigen-
binding region.
ii. For B cells to produce antibodies, they must be activated.
(a) Most common way this occurs is via helper T cells.
(1) Macrophage engulfs the antigen via phagocytosis. It digests the antigen, pushing
discarded particles to the cell surface where they interact with B cells and a
helper T cell.
(2) Antigen binds to the B cell and the helper T cell, activating both.
(3) Helper T cells secrete a lymphokine, which stimulates the B cell to produce a
clone (group of identical cells formed from the same parent cell).
(4) Clone comprises two identical cells that have two different functions; plasma
cells make antibodies, and memory cells remember the encounter with the
antigen
iii. Major histocompatibility complex: Group of genes located on a single chromosome that
distinguishes between foreign substances and its own cells and tissues
iv. Human leukocyte antigen gene complex: The human major histocompatibility complex
that encodes for numerous antigens that are unique to a person
9. Immunoglobins are antibodies secreted by B cells.
a. Consist of a crystallizable fragment (Fc) portion and two antigen-binding fragment (Fab)
regions
i. Bind only a specific antigen
b. The basic antibody molecule has four chains linked into a Y shape.
i. Each side is identical with one light chain attached to a heavy chain.
c. Three main categories of antigens on antibodies
i. Isotypic antigenic marker occurs in all members of a subclass of an immunoglobin class.
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ii. Allotypic antigenic marker is found on some members of a subclass of an immunoglobin
class.
iii. Idiotypic antigenic determinant is a unique structure created on the light and heavy chains
of an immunoglobulin molecule.
d. Most antibodies are found in the plasma.
i. Make up approximately 20% of the plasma proteins in a healthy person
e. Antibodies make antigens more visible to the immune system in three ways:
i. Opsonization: An antibody coats an antigen to facilitate its recognition by immune cells
ii. Antibodies cause antigens to clump for easier phagocytosis.
iii. Antibodies bind to and inactivate some toxins produced by bacteria so macrophages can
ingest them.
f. Antibodies divided into five general classes of immunoglobulins:
i. IgG accounts for 75% of the antibodies in the blood.
ii. IgA accounts for 15% of the antibodies in the blood.
iii. IgM accounts for 5% to 10% of the antibodies in the blood.
iv. IgE accounts for less than 1% of the antibodies in the blood.
v. IgD accounts for less than 1% of the antibodies in the blood.
vi. Refer to Table 9-4.
g. Fetal immunity: Passively acquired immunity derived from maternal IgG and IgM antibodies
10. Cell-mediated immune response
a. Cell-mediated immunity: Characterized by the formation of a population of lymphocytes that
can attack and destroy foreign material
b. Main defense against virus, fungi, parasites, and some bacteria
c. Mechanism by which the body rejects transplanted organs and eliminates abnormal cells that
sometimes arise
d. T cell lymphocytes recognize antigens and contribute to the immune response in two ways.
i. Secrete cytokines that attract other cells
ii. Become cytotoxic and kill infected or abnormal cells
e. Five subgroups of T cells
i. Killer T cells: Destroy the antigen
ii. Helper T cells: Activate immune cells, including B cells and other T cells
iii. Suppressor T cells: Suppress the activity of other lymphocytes so they do not destroy
normal tissue
iv. Memory T cells: Remember the reaction for the next time it is needed
v. Lymphokine-producing cells: Work to damage or destroy cells infected with a virus
D. Inflammatory response
1. Response of the tissues of the body to irritation or injury characterized by pain, swelling, redness,
and heat
a. White blood cells are a major component of this response.
b. Inflammatory reaction and immune response are independent processes although they often
occur simultaneously.
c. Two most common causes: infection and injury

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2. Acute inflammation
a. Involves both vascular and cellular components
i. Initially, the arterioles constrict in an attempt to limit blood loss, but then dilate.
ii. Allows an influx of blood under increased pressure and causes blood vessel to expand
iii. Vessel walls become thinner and fluid leaks into interstitial spaces (edema).
iv. When enough pressure has been released, vessel wall contracts and the flow slows,
leading to pooling of blood.
3. A variety of blood cells participate:
a. White blood cells (leukocytes)
b. Platelets
c. Mast cells
d. Plasma cells (B lymphocytes)
e. Specific cell types include neutrophils, monocytes, lymphocytes, eosinophils, basophils, and
activated platelets.
f. Chemical mediators account for the vascular and cellular events that occur.
i. Include histamine, arachidonic acid derivatives, and cytokines
4. Mast cells
a. Degranulate and release a variety of substances
i. Primary stimuli for degranulation are physical injury (trauma), chemical agents (eg,
bacterial toxins), and immunologic substances (eg, interaction of an antigen and an IgE
antibody).
b. Release vasoactive amines
i. Histamine and serotonin: Increase vascular permeability, cause vasodilation, and can
cause bronchoconstriction, nausea, and vomiting
c. Synthesize leukotrienes (slow-reacting substances of anaphylaxis)
i. Family of biologically active compounds derived from arachidonic acid
ii. Participate in host defense reactions and pathophysiologic conditions (immediate
hypersensitivity and inflammation)
iii. Primarily endogenous mediators of inflammation
iv. Contribute to the signs and symptoms seen in acute inflammatory responses
v. Certain leukotrienes are bronchoconstrictors, stimulate airway mucus secretion, and are
very effective at increasing the permeability of postcapillary venules.
d. Synthesize prostaglandins
i. Substances derived from arachidonic acid
ii. Comprise a group of about 20 lipids that are modified fatty acids attached to a five-
member ring
iii. Found in many vertebrate tissues
iv. Act as messengers involved in reproduction, the inflammatory response to infection, and
pain perception
5. Plasma protein systems: Plasma-derived mediators that modulate the inflammatory response
a. Complement system

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i. Group of plasma proteins that attract white blood cells to sites of inflammation, activate
white blood cells, and directly destroy cells
ii. C3: Central compound, produced by one of the two pathways
(a) Classic pathway: Starts when an antigen–antibody complex binds to a complement
component
(b) Alternative pathway: Triggered by bacterial toxins and does not need antibodies to be
activated
iii. Components include:
(a) C3b: Coats bacteria, making it easier for macrophages to engulf them
(b) Anaphylatoxins (C3a, C4a, and C5a): Stimulate smooth-muscle contraction and
increase vascular permeability
(c) Membrane attack complex (C5b, C6, C7, C8, and C9): Bind to form a hollow tube
that can puncture into the plasma membrane of a cell
b. Coagulation system
i. Serves a vital role in the formation of blood clots in blood vessels
ii. Inflammation triggers the coagulation cascade, a series of reactions that encourage fibrin
formation.
(a) Fibrin: Protein that polymerizes (bonds) to form the fibrous component of a blood
clot
(b) Fibrinolysis cascade: Activated to dissolve the fibrin and create fibrin split products
c. Kinin system
i. Leads to the formation of the vasoactive protein bradykinin from kallikrein
(a) Kallikrein: Enzyme normally found in blood plasma, urine, and body tissue in an
inactive state
(b) Bradykinin: Increases vascular permeability, dilates blood vessels, contracts smooth
muscle, and causes pain when injected into the skin
ii. Hageman factor: Spurs the kinin system into action
(a) Triggers intrinsic clotting cascade, which occurs when blood is exposed to collagen
or other substances
6. Cellular components of inflammation
a. Goal: For inflammatory cells (specifically polymorphonuclear neutrophils [PMNs]) to arrive
at the sites within tissue where they are needed
b. Involves two major phases:
i. Intravascular phase: Leukocytes move to the sides of blood vessels and attach to the
endothelial cells.
ii Extravascular phase: Leukocytes travel to the site of inflammation and kill organisms.
c. Cellular event sequence
i. Margination: Loss of fluid causes blood to increase in viscosity
(a) Blood flow slows and produces stasis.
(b) PMNs, which usually travel toward the center of the vessel, settle toward the sides.
(c) Leukocytes move toward the sides of blood vessels and bind to endothelial cells.
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ii. Activation: Mediators trigger the appearance of selectins and integrins on the surfaces of
endothelial cells and PMNs.
iii. Adhesion: PMNs attach to endothelial cells.
iv. Transmigration (diapedesis): PMNs permeate the vessel wall, passing into interstitial
space.
v. Chemotaxis: PMNs move toward the site of inflammation in response to chemotactic
factors.
7. Cellular products of inflammation
a. Cytokines: Products of cells that affect the function of other cells
i. Interleukins (include IL-1 and IL-2): Attract white blood cells to the sites of injury and
bacterial invasion
ii. Interferon: Protein produced by cells when they are invaded by viruses
b. Lymphokines: Stimulate leukocytes
i. Macrophage-activating factor stimulates macrophages to engulf and destroy foreign
substances.
ii. Migration inhibitory factor keeps white blood cells at the site of infection or injury until
they can perform their designated task.
8. Injury resolution and repair
a. Normal wound healing involves four steps:
i. Repair of damaged tissue
ii. Removal of inflammatory debris
iii. Restoration of tissues
iv. Regeneration of cells
b. Healing after injury or loss depends on the type of cells that make up the affected organ.
i. Labile cells: Divide continuously so organs derived from these cells heal completely
ii. Stable cells: Replaced by regeneration from remaining cells
iii. Permanent cells: Cannot be replaced; scar tissue is laid down instead
c. Wounds can heal by:
i. Primary intention: Occurs in clean wounds with opposed margins
ii. Secondary intention: Occurs in large, gaping or infected wounds
(a) More pronounced and prolonged inflammatory phase
9. Dysfunctional wound healing
a. Factors that lead to dysfunctional wound healing may be local or systemic:
i. Local factors include infection, an inadequate blood supply, and foreign bodies.
ii. Systemic factors include poor nutritional intake and hematologic abnormalities.
(a) Diabetes and acquired immunodeficiency syndrome (AIDS) affect the cells of the
immune system, increasing the chance for infections.
(b) Corticosteroids suppress the initial inflammatory response required for the proper
formation of scar tissue and increase the risk of wound infection.
(c) Wound separation slows down the healing process as healing needs to start over to
some extent.
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E. Chronic inflammatory responses

1. Causes include:
a. Unsuccessful acute inflammatory response to a foreign body
b. Persistent infection
c. Presence of an antigen
2. Associated with an infiltrate (pus) containing monocytes and lymphocytes
3. Usually involve tissue destruction and repair (or scar formation)
4. Events are similar to those in acute inflammation process but also include the growth of new
blood vessels (angiogenesis)

XI. Variances in Immunity and Inflammation

A. Hypersensitivity is any response of the body to any substance to which a patient has
increased sensitivity.
1. Allergy: Hypersensitivity reaction to the presence of an agent (allergen)
2. Autoimmunity: Production of antibodies or T cells that work against the tissues of one’s own
body
3. Isoimmunity: Formation of T cells or antibodies directed against the antigens on another person’s
cells
a. Typically after the transplantation of an organ or tissues
4. Transient neonatal diseases: Present at birth but eventually resolve
a. Examples include transient neonatal hyperglycemia, transient neonatal myasthenia gravis,
and transient neonatal neutropenia.
b. Occur due to pathogenic immunoglobulins passing from the pregnant woman to the fetus
5. Hypersensitivity reactions may be immediate or delayed, depending on the antigen and the type
of response the body mounts against it.
a. Type I: Immediate hypersensitivity reactions
i. Acute reaction that occurs in response to a stimulus
ii. Involves interaction between the stimulus and a preformed antibody of the IgE type
iii. Severity of symptoms depends on the extent of mediator release
iv. Propensity may be diagnosed through skin tests and laboratory procedures
v. Treatment in the field includes administration of epinephrine via epinephrine auto-
injector or subcutaneous injection.
b. Type II: Cytotoxic hypersensitivity
i. Involves the combination of IgG or IgM antibodies with antigens on the cell membrane
ii. Cells are destroyed by complement fixation or by other antibodies.
iii. Occurs within a few hours of exposure
iv. Examples include transfusion reactions and newborn hemolytic disease.
c. Type III: Tissue injury caused by immune complexes
i. Involves IgG antibodies that form immune complexes with the antigen to recruit
phagocytic cells to a site where they can release inflammatory cytokines

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ii. Occurs within a few hours of exposure
iii. Reactions may be systemic or localized.
(a) Systemic form (serum sickness) results from a large, single exposure to an antigen
(b) Localized form (Arthus reaction) consists of a circumscribed area of vascular
inflammation (vasculitis)
d. Type IV: Delayed (cell-mediated) hypersensitivity
i. Primarily mediated by soluble molecules that are released by specifically activated T
cells
ii. Subtypes:
(a) Delayed hypersensitivity involves lymphocytes and macrophages.
(b) Cell-mediated cytotoxicity involves sensitized T cells (CD8 lymphocytes or killer T
cells).
e. Refer to Table 9-6.
6. Targets of hypersensitivity reactions
a. Allergic reactions: Target is an antigen or allergen
b. Autoimmune reactions: Target is person’s own tissues
i. Graves disease: Autoimmune disease caused by thyroid-stimulating or thyroid-growth
immunoglobulins
ii. Type 1 diabetes mellitus: Some agent causes the body to produce autoantibodies against
beta cells.
iii. Rheumatoid arthritis: Chronic systemic disease
(a) One of the most common forms is characterized by inflammation of the synovium
(connective tissue membrane lining the joint).
(b) Inflammatory cells release enzymes that cause damage to bone and cartilage.
iv. Myasthenia gravis: Acquired autoimmune disease characterized by attack on the nerve-
muscle junction
v. Neutropenia: Decrease in circulating neutrophils
(a) Decreases the body’s ability to fight infection
vi. Idiopathic (or immune) thrombocytopenia purpura (ITP): Blood disorder in which
antibodies form to blood platelets and cause their destruction
(a) Bleeding is the main symptom.
(b) Treatment is based on severity of symptoms and platelet count.
vii. Systemic lupus erythematosus (SLE): Body’s own immune system is directed against the
body’s own tissues
B. Immune deficiencies
1. Immunodeficiency: Abnormal condition in which some part of the body’s immune system is
inadequate
a. Resistance to infectious diseases is decreased.
2. Congenital immunodeficiencies
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a. Defects involve lymphoid stem cells and affects both T and B cells
b. Both forms of this disease are inherited.
i. X-linked agammaglobulinemia (XLA): One of the most common forms of inherited
primary immunodeficiency and occurs predominantly in males
ii. Results in:
(a) Decreases in the level of all immunoglobulins and mature B lymphocytes
(b) Decreased ability to produce antibodies
(c) Decreased ability to effectively protect against bacteria and viruses
iii. Isolated deficiency of IgA: Results from a block in the terminal differentiation of B
lymphocytes
(a) Most common form of immunodeficiency
(b) Most patients are asymptomatic, but can have chronic sinus infections.
3. Acquired immunodeficiencies
a. Contributors to this condition include:
i. Nutritional deficiency
ii. Stress of trauma
iii. Hypoperfusion or shock
iv. Mediator production
v. Damage to vital organs
vi. Decreased nutrition occurring during trauma states
b. Iatrogenic (treatment-induced) immunodeficiency: most frequently caused by medications
i. Often of therapeutic benefit—however, may lead to other diseases
ii. Physicians are usually cautious about prescribing this therapy for a prolonged period.
iii. Idiosyncratic reactions to antibiotics may cause bone marrow suppression.
c. Physical or mental stress has been shown to decrease white blood cell and lymphocyte
function.
d. AIDS
4. Treatment of immunodeficiencies includes:
a. Replacement therapy available for some types
i. Intravenous gamma globulin: Used in therapy for a number of immunologic disorders of
the nervous system
ii. Bone marrow transplantation: Used in persons with acquired causes of immunodeficiency
iii. Transfusions

XII. Factors That Cause Disease

A. Genetic, environmental, age-related, and sex-associated factors can cause or contribute
to disease.
1. Genetic factors are present at birth and are passed through a person’s genes to future generations.
2. Environmental factors include microorganisms, immunologic vulnerabilities, personal habits and
lifestyle, exposure to chemicals and other toxins, the physical environment, and the psychosocial
environment.
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3. Anatomic causes include malrotation of the colon, degenerative diseases of the spine, or aortic
stenosis.
4. An immunologic reaction can cause disease. An example is an agent that triggers an abnormal
immune response against myelin, leading to the development of multiple sclerosis.
B. Controllable versus uncontrollable risk factors
1. Uncontrollable factors include genetics and race.
2. Controllable factors include smoking, drinking alcohol, inadequate nutrition, lack of physical
activity, and stress.
3. Age-related risk
a. Risk of a particular disease often depends on the patient’s age.
i. Newborns at risk because immune system not fully developed
ii. Teenagers at risk because of injury due to trauma, use of illicit drugs, and alcohol
iii. Older adults have increased risk of cancer, heart disease, stroke, and Alzheimer disease.
4. Sex-associated factors
a. Sometimes sex is related to the risk of having a certain disease.
i. Note that a person’s physical sex and gender are not necessarily the same.
ii. In this discussion, we are referring to a person’s genetic sex.
b. Presentation of disease can differ from men to women.
c. Genetic disorders are related to a person’s sex when the defective gene is located on a sex
chromosome.
i. Most sex-linked disorders are X linked.
C. Analysis of disease risk
1. Causal risk factors: Factors that can directly cause a disease to develop
2. Noncausal risk factors: Factors that are associated with risk for a disease but not a direct cause
3. All studies should consider the incidence, prevalence, morbidity, and mortality of the disease.
a. Incidence: Number of new cases of a disease in a population
b. Prevalence: Number of cases in a particular population within a particular period
c. Morbidity: Presence of disease or incidence or prevalence of a disease
d. Mortality: Number of deaths from a disease in a given population, expressed as a proportion
4. Risk factors often interact.
5. Refer to Table 9-10.
D. Common familial diseases and associated risk factors
1. Genetic risk: One that is passed through generations by inheritance of a gene
2. Familial tendency: Cluster of diseases in family groups despite lack of evidence for heritable
gene-associated abnormalities
3. Autosomal recessive: Pattern of inheritance that involves genes located on autosomes (a person
needs to inherit two copies of a particular gene)
4. Autosomal dominant: A person needs to inherit only one copy of a particular form of a gene to
show that trait
5. Immunologic disorders

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a. Caused by either hyperactivity or hypoactivity of the immune system
b. Most that exhibit familial tendencies involve an overactive immune system (allergies,
asthma, and rheumatic fever)
c. Allergies: Acquired following initial exposure to an allergen; repeated exposures cause the
immune system to react.
i. Person who has an allergic tendency is atopic.
d. Asthma: Chronic inflammatory condition resulting in intermittent wheezing and excess
mucus production
6. Cancer
a. Describes the pathology associated with malignant growths (neoplasms) in various anatomic
areas of the human body
b. Prognosis often depends on the extent of its spread (metastasis) and the effectiveness of
treatment.
c. Lung cancer
i. Major risk factor is cigarette smoking
ii. Eight alterations in genetic material of lung cancer that may suggest a genetic tendency
(a) Other predisposing factors include exposure to asbestos, coal products, and other
industrial and chemical products.
iii. Symptoms include cough, difficulty breathing, blood-tinged sputum, and repeated
infections.
iv. Treatment depends on type, site, and extent.
(a) May include surgery, chemotherapy, and/or radiotherapy
d. Breast cancer is the most common type of cancer occurring among women.
i. Women whose first-degree relatives have breast cancer are more likely to develop the
disease.
ii. Risk varies with the age at which the affected relative was diagnosed.
iii. 5% to 10% of patients have a pattern of autosomal dominant inheritance.
iv. Symptoms:
(a) Early: Small painless lump, thick or dimpled skin, change in nipple
(b) Late: Nipple discharge, pain, and swollen lymph glands in the axilla
v. Treatment depends on location, size, and metastasis of the tumor.
e. Colorectal cancer: Third most common type of cancer in both men and women
i. Relatives of patients with colorectal cancer are more likely to have the disease
themselves.
ii. Symptoms: May be minimal (small amounts of blood in the stool)
iii. Treatment involves surgery and sometimes chemotherapy.
7. Endocrine disorders
a. Diabetes mellitus: Chronic disorder of metabolism associated with either partial insulin
secretion or total lack of insulin secretion by the pancreas
i. Symptoms include excessive thirst and urination, weight abnormalities, and the presence
of excessive glucose in the urine and blood.

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b. Ketoacidosis-prone (type 1) diabetes: Insulin-dependent diabetes mellitus
c. Non–ketoacidosis-prone (type 2) diabetes: Non–insulin-dependent diabetes
d. There is no cure for type 1; type 2 can occasionally be brought under control with weight
loss, regular physical activity, and medications.
8. Hematologic disorders
a. Hemolytic anemia: Characterized by increased destruction of red blood cells
i. Several causes: Rh factor blood transfusion reaction, disorder of the immune system,
exposure to bacterial toxins or chemicals
b. Hemophilia: Inherited disorder characterized by excessive bleeding
i. Sex-linked condition (occurring predominantly in males), passed from asymptomatic
mothers to sons
ii. One of the blood-clotting proteins is missing or is present in abnormally low amounts.
c. Hemochromatosis: Inherited (autosomal recessive) disease in which the body absorbs more
iron than it needs
i. Excess iron is stored in various organs.
ii. Can lead to diabetes, heart disease, liver disease, arthritis, impotence, and a bronzed skin
color
9. Cardiovascular disorders
a. Long QT syndrome: Cardiac conduction system abnormality resulting in a prolongation of
the QT interval on the ECG
i. Inherited in an autosomal dominant manner
ii. Sometimes associated with congenital hearing loss, hypertrophic cardiomyopathy, or
mitral valve prolapse (MVP)
iii. Most patients are asymptomatic until they have a dysrhythmia causing syncope or sudden
death.
iv. Consider syncope to be due to a life threat until proven otherwise under the following
conditions:
(a) Exercise-induced syncope
(b) Syncope associated with chest pain
(c) History of syncope in a close family member
(d) Syncope associated with startle
b. Cardiomyopathy: Diseases of the myocardium that ultimately progress to heart failure, acute
myocardial infarction (AMI), or death
i. Heart muscle becomes thin, flabby, dilated, or enlarged.
ii. Hypertrophic cardiomyopathy is genetically autosomal dominant.
(a) Excessive thickening of the heart muscle
(b) Symptoms may include shortness of breath, chest pain, palpations, or syncope;
sudden cardiac death is also possible.
(c) Treatment includes beta blockers in some cases, or surgery or an implantable cardiac
defibrillator.
c. Mitral valve prolapse (MVP): Mitral valve leaflets balloon into the left atrium during systole.

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i. Often benign and asymptomatic
(a) Only physical finding may be a clicking sound heard during cardiac auscultation.
ii. May lead to a mitral regurgitation
(a) Large amount of blood leaks backward through the defective valve.
(b) Can lead to thickening or enlargement of the heart wall
(c) Patients feel tired or short of breath.
(d) Treatment can be medication and in some cases surgery to repair or replace the valve.
d. Coronary heart disease
i. Typically from occluded coronary arteries from atherosclerotic plaque buildup
ii. Familial tendency
iii. Other risk factors include hypercholesterolemia, cigarette smoking, hypertension, age,
and diabetes.
iv. Hypercholesterolemia: Elevation of the blood cholesterol level
e. Hypertension
i. Associated with an increased risk of coronary artery disease and stroke
ii. Risk factors can be genetic or lifestyle related.
(a) Include age, race, sex, family history, obesity or being overweight, sedentary
lifestyle, tobacco use, diet, and stress
iii. Stroke risk factors are also genetic or lifestyle related.
(a) Include age (55 or older), race (African Americans, Hispanics, and American
Indian/Alaska Natives), sex (men), family history, obesity or being overweight,
sedentary lifestyle, hypertension, hypercholesterolemia, tobacco use, diabetes,
cardiovascular disease, use of birth control pills or hormone therapies, and excessive
alcohol consumption
10. Renal disorders
a. Gout: Abnormal accumulation of uric acid due to a defect in metabolism
i. Accumulates in the blood and joints, causing pain and swelling
ii. More common among men than women and usually has a genetic basis
iii. Left untreated, causes destructive tissue changes in the joints and kidneys
iv. Treatment includes diet and medications.
b. Kidney stones: Small masses of uric acid or calcium salts that form in any part of the urinary
system
i. Four main types:
(a) Calcium oxalate
(b) Uric acid
(c) Struvite
(d) Cystine
ii. Often cause severe pain, nausea, and vomiting when the body attempts to pass them
iii. Researchers have found a gene that causes the intestines to absorb too much calcium.
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iv. Uric acid stones often have a genetic basis.
11. Gastrointestinal disorders
a. Malabsorption disorders: Caused by defects in the function of the bowel wall that prevent
normal absorption of nutrients
i. Complex symptoms include loss of appetite, bloating, weight loss, muscle pain, stools
with high fat content, and diarrhea that may be bloody.
ii. Lactose intolerance: Defect or deficiency in the enzyme lactase
(a) Inability to digest lactose (milk sugar)
(b) Symptoms include bloating, flatulence, abdominal discomfort, nausea, and diarrhea
on ingestion of dairy or dairy products.
iii. Ulcerative colitis: Serious chronic inflammatory disease of the large intestine and rectum
(a) Shows a familial tendency
(b) Recurrent episodes of abdominal pain, fever, chills, and profuse diarrhea, with stools
containing pus, blood, and mucus
(c) Treatment consists of anti-inflammatory agents and in some cases surgery.
iv. Crohn disease: Chronic inflammatory condition that affects one or more areas of the GI
tract, most often affecting the terminal part of the small intestine
(a) Exact cause is unknown, but possible causes include bacterial, viral, allergic,
autoimmune, and undetermined gene abnormalities
(b) Symptoms include frequent episodes of diarrhea, abdominal pain, nausea, fever,
weakness, and weight loss.
(c) Management includes nutrition therapy, anti-inflammatory agents, antibiotics, and
sometimes surgery.
b. Peptic ulcer disease: Circumscribed erosions (ulcerations) in the mucous membrane lining of
the gastrointestinal tract (specifically esophagus, stomach, duodenum, or jejunum)
i. May be associated with excess acid production or from a breakdown in the normal
mechanisms protecting the mucous membranes
ii. Appears to have a genetic component, but major contributor is infection with the
bacterium Helicobacter pylori
iii. Symptoms include gnawing pain (often worsened when the stomach is empty, after the
person eats certain foods, or when the patient is under stress).
iv. Treatment includes avoidance of irritants, antibiotics, medications to decrease acidity, or
surgery.
c. Gallstones (choleliths): Stonelike masses in the gallbladder or its ducts caused by
precipitation of substances contained in bile
i. Contributing factors include abnormalities in the composition of bile, or stasis of bile.
ii. May be asymptomatic or cause inflammation of the gallbladder, pain in upper right
quadrant or epigastric area, or jaundice
d. Obesity: Unhealthy accumulation of body fat
i. Body mass index (BMI) of greater than or equal to 30 kg/m2
ii. Three classes (health risks increase with each increase in class):

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(a) Class 1: BMI of 30 kg/m2 to less than 35 kg/m2
(b) Class 2: BMI 35 kg/m2 to less than 40 kg/m2
(c) Class 2: BMI 35 kg/m2 to less than 40 kg/m2
iii. Morbid obesity: Body mass index of greater than or equal to 40 kg/m2
(a) Includes all the health risks of obesity but makes essential life functions such as
walking or breathing difficult
iv. Overweight: Body mass index of 25 to 29.9 kg/m2
v. Health risks include hypertension, hyperlipidemia, cardiovascular disease, glucose
intolerance, insulin resistance, diabetes, gallbladder disease, infertility, and cancer of the
endometrium, breast, prostate, and colon.
vi. Social and psychological effects include depression, anxiety, shame, rejection, and
discrimination.
vii. Although there may be a genetic predisposition to obesity, behavioral and environmental
factors are better known.
(a) Sedentary lifestyle, overeating, or choosing foods high in calories and low in
nutritional value
12. Neuromuscular disorders
a. Huntington disease (also called Huntington chorea): Hereditary condition characterized by
progressive chorea and mental deterioration, leading to dementia
i. Symptoms usually first appear in the third or fourth decade and progress to death often
within 15 years.
b. Muscular dystrophy: Generic term for a group of hereditary diseases of the muscular system
i. Characterized by weakness and wasting groups of skeletal muscles, leading to increasing
disability
ii. Various forms differ in age of onset, rate of progression, and mode of genetic
transmission.
iii. Duchenne muscular dystrophy: Sex-linked recessive disease (affecting only males)
c. Multiple sclerosis: Progressive disease in which the myelin sheath surrounding the nerve
fibers of the brain and spinal cord become damaged
i. Not directly inherited, but patients may have familial predisposition
ii. Usually appears in early adulthood and progresses slowly, with periods of remission and
exacerbation
iii. Symptoms include abnormal sensations in the face or extremities, weakness, visual
disturbances, ataxia, abnormal reflexes, tremors, difficulty urinating, and difficulty
walking.
iv. No specific treatment or cure; corticosteroids and other drugs are used to treat symptoms
d. Alzheimer disease: Unknown cause
i. Results in cortical atrophy and loss of neurons in the frontal and temporal lobes of the
brain. Additionally, as the brain ventricles become enlarged, a loss of brain tissue occurs.
ii. Studies of the genetics of inherited early-onset Alzheimer disease have been linked to
mutations on three genes.

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iii. Progressive disease
(a) Early symptoms include memory loss, lack of spontaneity, subtle personality
changes, and disorientation to time and date.
(b) Advanced symptoms include indifference to food, inability to communicate, urinary
and fecal incontinence, and seizures.
13. Psychiatric disorders
a. Schizophrenia: Group of mental disorders characterized by gross distortions of reality
(psychoses), withdrawal from social contacts, and disturbances of thought, language,
perception, and emotional response
i. Symptoms are highly varied.
ii. No identified cause
(a) Combination of hereditary or genetic predisposing factors is likely
b. Bipolar disorder: Mental disorder characterized by episodes of mania and depression
i. Evidence of role of genetics
ii. Treatment consists of psychotherapy plus antidepressants and tranquilizers.

XIII. Stress and Disease

A. Stress is the medical term for a wide range of strong external stimuli that can cause a
physiologic response.
1. Physiologic stress: A change that makes it necessary for the cells of the body to adapt
a. Three concepts include:
i. The stressor
ii. Stressor’s effects on the body
iii. Body’s response to the stress
b. Usually, response to stress is appropriate and beneficial.
i. Unchecked stress response can result in deleterious outcomes, including:
(a) Chemical dependency
(b) Heart attack
(c) Stroke
(d) Depression
(e) Headache
(f) Abdominal pain
B. General adaptation syndrome
1. Identified by Hans Selye in the 1920s
2. Comprises a three-stage reaction to stressors
a. Stage 1: Alarm
i. Body reacts by releasing catecholamines, such as epinephrine (adrenaline),
norepinephrine (noradrenaline), and dopamine

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(a) Adrenaline: Acts as a neurotransmitter in the CNS and as a hormone in the blood
(b) Noradrenaline: Primarily a neurotransmitter of the peripheral sympathetic nervous
system
ii. Catecholamines activate the sympathetic nervous system by binding to receptor sites.
(a) Alpha receptor activation results in vasoconstriction.
(b) Beta receptor activation results in increased heart rate, increased force of contraction,
and increased conduction velocity.
iii. Other effects include increased respiratory rate, decreased blood flow to the skin, smooth-
muscle constriction, and various effects on the liver that increase the body’s use of
glucose.
iv. Fight-or-flight response can either prepare the body to deal with stress or weaken the
immune system.
b. Stage 2: Resistance or adaptation
i. Body’s way of adapting to stressors
ii. Stimulates the adrenal gland to secrete two types of corticosteroid hormones that increase
blood glucose level and maintain blood pressure:
(a) Glucocorticoids
(b) Mineralocorticoids
iii. Hypothalamus stimulates the anterior pituitary gland to release adrenocorticotropic
hormone (ACTH).
(a) ACTH targets the adrenal cortex to release cortisol.
(1) Stimulates cells to increase energy production
(2) Increases serum glucose levels and impairs the use of glucose by peripheral
tissues
(3) Decreases protein reserves and permits mobilization of fatty acids
(4) Reduces inflammation when it has served its purpose
(5) Increases red blood cell production and affects electrolyte levels
(6) Decreases size of lymphoid tissue, which plays a role in immunity
iv. Other hormones related to stress include:
(a) Endorphins: Reduce pain and stress
(b) Growth hormone: Promotes cell and tissue growth and repair; reduced in times of
stress
(c) Prolactin: Levels increase more in people with ineffective coping mechanisms
(d) Testosterone: When cortisol levels are high, testosterone levels are low
v. Cortisol levels and sympathetic nervous system should return to normal during resistance
or adaptation stage.
vi. Continuation of stress and accompanying corticosteroid release lead to fatigue, lapses in
concentration, irritability, lethargy, depression, and a depressed immune system.
c. Stage 3: Exhaustion
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i. Adrenal glands become depleted, decreasing the level of blood glucose
ii. Results in:
(a) Decreased stress tolerance
(b) Progressive mental and physical exhaustion
(c) Illness
(d) Collapse
iii. The body’s immune system is compromised, significantly reducing the ability to resist
disease.
C. Effects of chronic stress
1. Hypothalamic-pituitary-adrenal axis: Major part of the neuroendocrine system that controls
reactions to stress
a Triggers a set of interactions among the glands, hormones, and parts of the midbrain that
mediate the general adaptation syndrome
b. Continued stress leads to loss of these normal control mechanisms
i. Continued production of cortisol exhausts the stress mechanism and leads to fatigue and
depression.
(a) Consistently high levels lead to suppression of the immune system.
2. Stress and depression have a negative effect on the immune system.
a. Causes the body to lose its ability to fight disease
b. Encourages the body to release fat and cholesterol into the bloodstream, eventually causing
heart attacks or stroke
c. Related conditions include:
i. Depression
ii. Headaches
iii. Insomnia
iv. Ulcers
v. Diuresis
vi. Acne
vii. Diabetes mellitus
viii. Rheumatoid arthritis
ix. Asthma
3. Coping mechanisms play a role in the physiologic response to stress.
a. Healthy person may manage stress with minimal adverse effects on the immune system.
b. Patient with ineffective coping mechanisms will have deleterious effects on immune status.
c. Effects are worse on a person with an already compromised immune system.
4. Immune suppression can be corrected with:
a. Psychotherapy
b. Medication
c. Other positive influences that restore hope and a feeling of self-esteem

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Post-Lecture
This section contains various student-centered end-of-chapter activities designed as enhancements to the
instructor’s presentation.

Assessment in Action
Assessment in Action is available to students in the Navigate course. This practice activity is designed to
assist the student in gaining a further understanding of issues surrounding the provision of prehospital
care. The activity incorporates both critical thinking and application of paramedic knowledge.

Assignments
A. Review all materials from this lesson and be prepared for a lesson quiz to be
administered (date to be determined by instructor).
B. Read Chapter 10, Life Span Development, for the next class session.

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