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PATHOPHYSIOLOGY: A REVIEW OF KEY

CONCEPTS FOR EXAM PREPARATION

Marnie Kramer-Kile RN, PhD

PATHOPHYSIOLOGICAL REVIEW ALLOWS YOU

TO:

• Predict outcomes related to pathology

• Focus in on specific assessment findings

• Understand diagnostic testing for pathology

• Predict interventional strategies

• Understand potential outcomes for the client

KEY AREAS FOR REVIEW IN THIS LECTURE

• Cellular Injury

• Inflammation

• Hypersensitivity Reactions

• Mechanisms of Hypoxemia

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PART ONE: CELLULAR INJURY

CELLULAR RESPONSE TO INJURY

Reversible: mild or short lived injury

Adaptation: persistent but sub lethal injury that cause the cells to adapt (i.e. hypertrophy)

Cell death: due to prolonged and serve injury that is irreversible.

Results in: Necrosis or Apoptosis

CELLULAR INJURY - PATHOGENESIS

• Direct cellular injury

• Indirect cellular injury

Three mechanisms

1) Free radical formation

2) Hypoxia & ATP depletion

3) Disruption of intracellular calcium homeostasis

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CELLULAR INJURY – PATHOGENESIS –

1) FREE RADICAL FORMATION

• Unstable molecule –

unpaired electrons

• Free radicals bond with other

molecules to form stable

molecules

• Many metabolic processes

result in free radical

formation

• Oxygen radicals

http://www.healthchecksystems.com/antioxid.htm

CELLULAR INJURY – PATHOGENESIS –

FREE RADICAL FORMATION

• Oxygen radicals cause injury by:

• Lipid peroxidation

• Cell membrane permeability altered

• Oxidative modification of proteins

• Enzyme functions altered

• Fragmenting DNA

• Direction of cellular activities interrupted

• Mitochondrial damage

• Altered ATP production

WHY IS THIS IMPORTANT?http://edcenter.med.cornell.edu/CUMC_PathNotes/Cell.Injury/Cell_Injury.html

http://edcenter.med.cornell.edu/CUMC_PathNotes/Cell.Injury/Cell_Injury.html

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CELLULAR INJURY – PATHOGENESIS –

2) HYPOXIA & ATP DEPLETION

• Hypoxia

• ↓ oxygen in blood & tissues

• Wide spread effects throughout the body

• Ischemia

• ↓ blood flow to tissues

• ↓ oxygen delivery

• ↓ nutrient delivery

• ↓ waste removal

• Localized effects

CELLULAR INJURY: REVERSIBLE

• Hypoxia

• impaired aerobic respiration

• ↓ ATP (energy)

• anerobic glycolysis

• glycogen depletion

• accumulation of lactic acid

CELLULAR INJURY – PATHOGENESIS – HYPOXIA

& ATP DEPLETION

CHO CHON Fat

Pyruvate

Acetyl CoA

2 ATP

anae

rob

icC

ell c

yto

pla

smae

rob

icm

ito

cho

nd

ria

KrebsCycle

oxygen36 ATP

Cellular work

glycolysis

Rev

iew

of

Cel

lula

r M

etab

olis

m

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SODIUM/POTASSIUM PUMP

CELLULAR INJURY – PATHOGENESIS – HYPOXIA

& ATP DEPLETION

• Failure of Na+/K+ exchange pump

• ↑ intracellular Na+

• ↓ intracellular K+

• ↑ membrane permeability

• Water moves into cell

• ↓ mitochondrial function

NOTE_ this is also the cause of hydropic swelling

CELLULAR INJURY – PATHOGENESIS –

3) CALCIUM HOMEOSTASIS DISRUPTION

• Ca++/Mg++ pump is ATP dependent

• No ATP = ↑ intracellular Ca++

• Ca++ stimulates

• enzymes that destroy cell structures & membrane

• ATPases that further destroy ATP

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CELLULAR INJURY IN HYPOXIA – PATHOGENESIS

Adaptation

Na/K pump failureCellular swelling

Reversible Irreversible

Cell death

Enzyme & protein leakageCa/Mg pump failure

Time Line0 min ? min

CAUSES OF ISCHEMIA

• Interruption of blood flow to an area (embolic stroke,

coronary artery disease, compartment syndrome)

• Heart failure

• Lung disease

• RBC disorders

What causes temporary ischemia to be prolonged?

(Copstead et al., 2010, p.75)

COMPARTMENT SYNDROME

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MYOCARDIAL ISCHEMIA

CEREBRAL ISCHEMIA

USD316.K12.KS.US/.../VALERIE/HOMEFRAME.HTML

TEMPORARY VS PERMANENT ISCHEMIA

(EXAMPLE ISCHEMIC PENUMBRA)

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CLINICAL PRESENTATIONS OF HYPOXIA

(LEADING TO ISCHEMIA)

• Hypotension (sys less 90 mmHg)- will be seen if shock state

from hypoxia occurring

• Tachycardia (increased HR to increase blood supply)

• Tachypnea (to increase intake O2)

• Cold clammy or mottled skin (result of hypoxia start of shock

state)

• Decreased urine output (start of shock state)

• Confusion (low O2)

• PaO2 low (can also detect low SaO2)

PART TWO: INFLAMMATION

THE INFLAMMATORY RESPONSE HAS THREE

PURPOSES

1. Neutralize and destroy invading and harmful agents

2. To limit the spread of harmful agents to other tissue

3. To prepare any damaged tissue for repair

(Adams et al., 2010, p.197)

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INJURY LEADS TO :

Cardinal Signs of Inflammation

- Redness

- Swelling

-Heat

-Pain

- Loss of Function

6.Phagocytosis

5.Emigration of neutrophils &

macrophages into tissue

4.Vasodilation

3. Release of Chemokines

2. Release of vasoactive chemicals

1. Endothelial Binding of neutrophils & microphages

CHEMICAL MEDIATORS INVOLVED IN

INFLAMMATION

• Cytokines

• Complement

• Histamine

• Leukotrienes

• Kinins

• Prostaglandins

• Clotting Factors

• Localized response

• Exudate formation

• Abscess formation

• Ulcer formation

• Systemic response

• Acute phase response

• Fever

• Skeletal muscle

catabolism

• Lethargy

• Leukocytosis

ACUTE INFLAMMATORY RESPONSE

LOCALIZED VS. SYSTEMIC RESPONSE

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INFLAMMATORY RESPONSE

• Laboratory Diagnosis

• (serum bloodwork)

• C-reactive protein (CRP)

• ESR

• Erythrocyte sedimentation rate

CHRONIC INFLAMMATORY RESPONSE

• Persists beyond 2 weeks

• Etiology

• Repeated injuries

• Persistent low grade injury that does not

stimulate “full blown” acute inflammatory

response

CHRONIC INFLAMMATORY RESPONSE

• Pathogenesis

• Neutrophils do not move in

• Macrophages & lymphocytes persist

• Fibroblasts proliferate

• 2 types:

• Nonspecific chronic inflammation

• diffuse

• scar tissue formation

• Granulomatous chronic inflammation

• Macrophages + lymphocytes + collagen + fibrin = granuloma

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PART 3: HYPERSENSITIVITY REACTIONS

Type IgG IgA IgM IgD IgE

% of Total

Immunoglo-

bulins

75% 15% 10% 0.2% 0.004%

Part of the

body where

it is found

Action

Serum, tissues

Role in

bloodborne,

tissue infections,

enhances

phagocytosis

activates

complement

system

Body fluids

Protects

against GI,

Resp, GU

infections

Prevents

absorption

antigens from

food

Intra-vascular

serum

First immuno-

globulin

produced in

response to

bacterial and

viral infections

Activates

compliment

Serum

Role

unclear

May influ.

B cell

different-

itation

Serum

Allergic and

some hyper-

sensitivity

reactions

Combats

parasitic

infections

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Too big immune response!!!

exaggerated, inappropriate

HYPERSENSITIVITY DISORDERS

HYPERSENSITIVITY DISORDERS

(TABLE 10-2, COPSTEAD, 226)

• Antigen

• Protein particle capable of triggering immune response

• 4 types

• Type I hypersensitivity

• Type II hypersensitivity

• Type III hypersensitivity

• Type IV hypersensitivity

SUMMARY

Type I Type II Type III Type IV

Mediated by IgE IgM or IgG IgG T lymphocytes

Complement

Activation

No Yes Yes No

Peak Action 15-30 min 15-30 min 6 hrs 24-48 hrs

Causes of

reaction

T-cell

deficiency

Abnormal

mediator

feedback

Exposure Ag or

foreign tissue,

cells, or graft

Persistent

infection-microbe

Ag

Extrinsic Envir

Autoimmunity

Intradermal Ag

Epidermal Ag

Dermal Ag

Manifestations Asthma,

rhinitis, atopic

eczema, bee-

sting reaction

ABO transfusions,

hemolytic disease

newborn,

myasthenia gravis

Glomerulonephritis,

SLE

Vasculitis

TB test

Contact

dermatitis

MS

Guillain- Barre

disease

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HTTP://IMAGE.SLIDESHARECDN.COM/HYPERSENSITIVITYREACTIONSLECTURENOTES-110703093904-

PHPAPP02/95/HYPERSENSITIVITY-REACTIONS-LECTURE-NOTES-4-728.JPG?CB=1309686120

PART FOUR: HYPERCAPNIA AND

MECHANISMS OF HYPOXEMIA

NORMAL PULMONARY CIRCULATION

http://www.bg.ic.ac.uk/Staff/khparker/homepage/BSc_lectures/2002/_Cardiovascular_Mechanics_2003.html

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REVIEW

• Lungs

• Hgb releases CO2

• Hgb invites O2

• Body tissue

• Hgb releases O2

• Hgb invites CO2

• Overall

• CO2 and O2 move from an area of high concentration to an area of low concentration.

http://webschoolsolutions.com/patts/systems/lungs.htm

• Altered breath sounds

• Dyspnea

• Abnormal breathing

• Hypoventilation

• Hyperventilation

• Sputum

• Cough

• Hemoptysis

• Cyanosis

• Pain

• Clubbing

WHAT ARE CLINICAL MANIFESTATIONS OF

PULMONARY ALTERATIONS?

ARTERIAL BLOOD GAS INTERPRETATION

Ph (7.35- 7.45) Throughout Body

PaCO2 (35-45 Meq/L) Lungs

HCO3 (22-26 Meq/L) Kidneys

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ARTERIAL BLOOD GAS INTERPRETATION

Ph acidosis (7.35- 7.45) alkalosis

PaCO2 alkalosis (35-45 mmHg) acidosis

HCO3 acidosis(22-26 mEq/L) alkalosis

RESPIRATORY DYSFUNCTION

• Failure to maintain adequate oxygenation.

• Manifested with:

→ Hypercapnia leading to respiratory acidosis.

→ Hypoxemia (4 mechanisms)

1. Hypoventilation

2. Diffusion disturbances

3. Shunts

4. V/Q mismatch

• carbon dioxide in the blood.

• Measured by arterial blood gas (PaCO2).

• Causes:• Nervous system,

• Thoracic alterations,

• Airway obstruction:

• WOB.

• physiological dead space.

• Effects of hypercapnia:

• Respiratory acidosis

• Altered electrolytes

• Arrhythmias

• intracranial pressures

• Somnolence

• Coma

• Headache• Hypoxemia

HYPERCAPNIA

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K+K+

K+ K+

K+CO2 + H2O = HCO3 + H+

H+

K+

H+ and K+ exchange serum K+

Tissue Cell

EXAMPLE OF ALTERED ELECTROLYTES

HYPOXEMIA

• Deficient blood oxygen levels

• Measured by:

• PaO2 (mmHg).

• Oxygen saturation (%).

MECHANISMS OF HYPOXEMIA

1. Hypoventilation.

2. Diffusion Disturbance.

3. Shunt.

4. Ventilation/Perfusion Mismatch.

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MECHANISMS OF HYPOXEMIA

1. HYPOVENTILATION

Alveolar ventilation is insufficient to sustain alveolar & arterial PO2 .

air going into lungs

pressure gradient

Air

flow

PaO2 PaCO2

Venous Arterial

O2 CO2

100 40

O2 CO2

40 46

NORMAL PRESSURE GRADIENT

95 42

Lung/alveoliAlveolar

PAO2 = 100 mmHg

PACO2 = 40 mmHg

Venous

PvO2 = 40 mmHg

PvCO2 = 46 mmHg

Arterial

PaO2 = 95 mmHg

PaCO2 = 42 mmHg

http://www.lung.ca/copd/anatomy/normal.

html

A. Barkman (2004)

Venous Arterial

O2 CO2

60 45

O2 CO2

40 48

REDUCED PRESSURE GRADIENT

58 46

Hypoventilation Lung

A. Barkman (2004)

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HYPOVENTILATION

• Example of Causes

• Medications

• Pleurisy

• Thorax muscular weakness

• Management

• Narcotic antagonists

• ↑ inspired oxygen

• Mechanical ventilation

Pleurisy: Inflammation

of the pleura.

MECHANISMS OF HYPOXEMIA 2.DIFFUSION DISTURBANCE

Diffusion of gas across respiratory membrane normally depends on:

◦ Pressure gradient.

◦ Surface area through which diffusion occurs.

◦ Solubility of gas.

◦ Distance over which diffusion occurs.

Venous Arterial

DIFFUSION

Surface area

O2 CO2

Distance over which diffusion occurs

Lung

A. Barkman (2004)

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Venous Arterial

DIFFUSION

Surface area

O2 CO2

Distance over which diffusion occurs

Reduced surface area

Lung

A. Barkman (2004)

Venous Arterial

DIFFUSION

Surface area

O2 CO2

Distance over which diffusion occurs

Lung

A. Barkman (2004)

Venous Arterial

DIFFUSION

Surface area

O2 CO2

Distance over which diffusion occurs

Lung

Increased distance

A. Barkman (2004)

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DIFFUSION DISTURBANCE

• Example of Causes

• Alveolar cell carcinoma

• Interstitial Fibrous

• Pulmonary edema

Edema in the Lungs

DIFFUSION DISTURBANCE: INTERSTITIAL

LUNG FIBROSIS

http://www.umwa.org/blacklung/intro.shtml

Sarcoidosis

http://edcenter.med.cornell.e

du/CUMC_PathNotes/Respir

atory/RESPLIST.html

PULMONARY EDEMA

http://www.biovisuals.com/alveolus.html

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DIFFUSION DISTURBANCE

Management

◦ Correct cause.

◦ Administer oxygen.

◦ Manage fever, heart rate, activity etc.

◦ Correct distance & surface area

when possible.

MECHANISMS OF HYPOXEMIA3. SHUNT

• Blood which arrives at the left ventricle without coming in contact with ventilating alveoli.

TYPES OF SHUNTS

• Anatomical shunt: • Congenital cardiac heart

defects.

• Increased flow through bronchial veins.

• Physiologic shunt:• Mismatching of V/Q ratio.

• Cause:

• Destructive lung disease that impairs ventilation.

• Cardiac failure which interferes with movement of blood through the lungs.

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ANATOMICAL SHUNT

PHYSIOLOGICAL SHUNTHTTP://WWW.BELTINA.ORG/HEALTH-DICTIONARY/HEART-FAILURE-CONGESTIVE-SYMPTOMS-TREATMENT-DIAGNOSIS.HTML

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3. SHUNT

Jim McGraw -http://www.tccd.net/south/faculty/jmcgraw/ARDS/sld006.htm

3. SHUNT

• Examples

• Atelectasis

http://www.emedicine.com/med/topic180.htm

Atelectasis

www.path.vghtpe.gov.tw/ Museum/Mu-

0501.htm

Atelectasis: “Incomplete expansion or collapse

of alveoli, caused by hypoventilation, obstruction ”

of the airways, or compression (Day, 2007, p. 521)

PULMONARY

EDEMA

http://www.biovisuals.com/alveolus.html

http://yalenewhavenhealth.org/hwdb/images/

hwstd/medical/pulmonol/n1619.jpg

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Jim McGraw - http://www.tccd.net/south/faculty/jmcgraw/ARDS/sld012.htm

3. SHUNT

• Examples

• Atelectasis

• Pulmonary edema

• Localized pneumonia

Pneumonia: Inflammation or infection

in the lung structures.

Example: alveoli & bronchioles

LOCALIZED PNEUMONIA

http://www.sbpt.org.br/leigos/pneumonia.htm

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3.SHUNT

• Examples

• Atelectasis

• Pulmonary edema

• Localized pneumonia

• Aspiration

• Management

• ↓ amount of shunt

• Open up non-ventilating alveoli

• Treat causeAspiration: Drawing in

foreign material into the lungs

MECHANISMS OF HYPOXEMIA

4. VENTILATION/PERFUSION (V/Q) MISMATCH

Mismatch of ventilation to perfusion.

Most common cause of hypoxemia in chronic and acute lung disease.

Arises when some regions of the lungs are hypoventilated or hypoperfused.

• Management

• Administer oxygen

• Correct the cause

• Examples:

• Pulmonary edema

• Aspiration

• Atelectasis

• ARDS

• COPD

• Pleural abnormalities

MECHANISMS OF HYPOXEMIA

4. VENTILATION/PERFUSION (V/Q) MISMATCH

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SUMMARY OF KEY CONCEPTS

• Cellular injury

• Inflammation

• Hypersensitivity reactions

• Hypercapnia

• Mechanisms of Hypoxemia

QUESTIONS?

REFERENCES

Adams, M.P., Holland, L.N., Bostwick, P.M. & King (2010). Pharmacology for nurses: A pathophysiologic approach (Canadian ed). Toronto, ON: Pearson.

Copstead, L.C. & Banasik, J. L. (2010). Pathophysiology (4th ed.). St. Louis: Elsevier Canada.

Day, R., Paul, P., Williams, B., Smeltzer, S., & Bare, B. (2007, 2010). Brunner & Suddarth’s textbook of medical-surgical Nursing. Philadelphia: Lippincott Williams & Wilkins.