Pathophysiology Exam 3: Inflammation & Healing Study Set

**Which two defenses are nonspecific defenses?** **"On Exam"**)

First line and second line of defense

- They are not designed for anything new in nature; they have not been exposed to. Ex: COVID-19 (they have no memory of COVID-19, they are not equipped to fight this off because they know nothing about this)

Example: If you go to a country where there is a new disease, and your body has never been exposed to it. These two defense systems cannot fight off something new because they do not recognize it. They only do generalized protection.

*Innate immunity (First line of defense)*

The immunity you are BORN with... nonspecific defense

Innate protects us from the outside world. They are a physical barrier

**Everything outside of you before it enters your body must go through the first line of defense. The skin and the mucus in your nares and mouth, chemicals in the blood, and immune system are all a part of the first line of defense.

It protects whatever is outside of your body from entering

Refers to nonspecific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body

*Once a pathogen enters the body, what line of defense does this trigger?*

Second line of defense.

Once it crosses in, it will no longer be the first line of defense

*Once something enters your body that your body does not recognize, it will trigger*

Inflammation

Inflammation is what line of defense?

second line of defense

Inflammation is how your body?

Heals

If the second line defense fails and this is a new disease your body has been exposed to, what defense do you need to protect you?

Third line of defense

**What is the only specific defense?**

Third line of defense

What is the third line of defense?

Adaptive (acquired) (specific) immunity

It has the ability to create antibodies (antigens) using B-cells. They also have T-cells that will attack that new virus that came in.

The third line of defense job is to understand this new pathogen in your body, create memory for it, and suppress it all at the same time.

Why do infants have a weak immune system?

They do not have a strong third line of defense, and they do not have the ability to fight it. The T-cells and B-cells have not been well developed.

Why do the elderly have a weak immune system?

The B-cells and the thymus glands get smaller as we age so it is not as effective. Nature sets us up to DIE. The immune system weakens as you get older.

What does the innate immune system include? (**"Make sure to go over"**)

First line - Physical barriers (skin, mucous membranes, chemicals)... protects from outside

Second line - Cell-derived defenses (phagocytes, complement proteins, interferons, inflammation, fever)... components of inflammation - when something ENTERS the body

*What do the non-specific defenses in our body make up? What do they protect from?*

They make up the innate immune system. They are not SPECIFICALLY direct against any one pathogen; they provide a guard against all infections (generalized)

What is the most important nonspecific defense/ physical barrier of the human body?

Skin

What does the first line of defense also include that you may not think would be first line of defense?

Linings of the gastrointestinal, genitourinary, and respiratory tracts (mucus and cilia trap microorganisms are filters)

Expelled through coughing/sneezing, urination, vomiting/defecation

Secrete saliva, tears ( when something gets in your eye, you get teary-eyed to protect us) , earwax, sweat, and mucus

*On Exam*

If a patient coughs, if they have mucus buildup, urination, vomiting

They will get rid of it. This is all a part of the first line of defense

Mucus and Cilia

Once an allergen enters, the allergen will trigger us to have extra mucus

First Line of Defense (2 of 2)

•Lysozymes attack bacteria

•Lysozyme is a naturally occurring enzyme found in bodily secretions such as tears, saliva, and milk. It functions as an antimicrobial agent.

•Antimicrobial peptides kill bacteria, fungi, viruses

•Defensins and collectins

•Defensins are members of a large family of cationic antimicrobial peptides that form an essential element of innate immunity.

Collectins can interact with receptors on host cells. Binding of collectins to microorganisms may facilitate microbial clearance

*Interferons* (Important)

Group of signaling proteins made and released by host cells (a living cell in which a virus multiplies) in response to the presence of several viruses

Once something foreign comes in, it will signal all of the proteins that are a part of the immune system to be activated. They are letting it be known something is WRONG

**The first line of Defense (Select All that Apply)**

a. Nonspecific

b. Mechanical barrier

c. Unbroken skin and mucous membranes

d. Secretions such as tear and gastric juices

**The second line of defense (Select All that Apply)**

a. Nonspecific

b. Phagocytosis

c. Inflammation

**What is phagocytosis?**

The process by which certain living cells called phagocytes ingest or engulf other cells or particles.

WBC, macrophages, neutrophils that engulf the actually pathogens

**Third line of defense** (Ding, DIng, DIng)

Specific defense

Production of specific antibodies or cell-mediated immunity

**What makes up the third line of defense?**

lymphocytes

- T-lymphocytes

- B-lymphocytes

Lymphocytes (**must know**)

A type of white blood cell found in the blood or lymph nodes

**Made by bone marrow**

Example: If you have leukemia, nine times out of ten, you will die because that type of cancer suppresses the bone marrow. If the bone marrow is suppressed, you will be unable to produce T-cells and B-cells.

Reverse precautions for this patient. You will have to wear the mask because they have a weak immune system so we are a danger to them (3rd line defense suppressed, cancer in the bone marrow)

T-Lymphocytes (**Must know**)

Recognize antigens on pathogens and either attack them directly or coordinate the activity of other cells of the immune system

Cell mediated immunity... attack directly

DO NOT DEVELOP ANTIBODIES... role is to ATTACKWHat

On exam

Which lymphocyte attacks the cell directly? (cell-mediated)

T-lymphocytes/T-cells

On exam

Which lymphocyte creates antibodies?

B-lymphocytes/B-cells

When T-cells attack the cell

B-cells attach and download the information

B-lymphocytes (**Must know**)

Produce antibodies (having the disease)

Recognize antigens and produce special chemicals called antibodies

They tag antigens and formulate a "memory" for the body to know how to attack the antigen again in the future

If you are given a vaccine this means you have the

virus

On the Exam

The answer for fever is

systemic

3 lines of defense summary

On Exam

First Lines of Defense

How do histamines affect blood vessels?

**Vasodilate**

Increased capillary permeability (edema)(want WBC to come out of blood vessels to go to the site of injury). It opens up so everything comes out so we can fight off the infection.

Ding Ding Ding

Histamine is part of the inflammatory response. If you took an anti-histamine it will stop the whole inflammatory response.

What is extravasation?

Is the leakage of a fluid from its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the tissues surrounding them.

What are the five hallmark signs of inflammation - second line of defense? (**on exam**)(select all that apply)

1. Heat (capillary widening - increased blood flow)(in vasodilation the blood pressure drops)

2. Redness

3. Swelling (Increased permeability (muscle walls loosen) - fluid release into tissues)(Protein leaves which should not be going out because it pulls water with it)(Edema)

4. Tenderness (fluid build up is putting pressure on nervous system around site of injury)

5. Pain (tenderness and pressure)

What is inflammation?

Wide variety of physiologic and pathologic responses intended to eliminate the initial cause of cell injury (tissue injury), remove the damaged tissue, and generate new tissue

How the body responds to cell injury and how the body removes damage tissue

Inflammation can be healthy. It is only unhealthy if it is excessive.

Inflammation process sets the stage for...

The events that will eventually heal the damaged tissue.

Thus, inflammation is intimately interwoven with the repair processes that replace damaged tissue or fill in the residual defects with fibrous scar tissue

Antivirals only work on

Viruses

Antibiotics only work on

Bacterial

Anything ending with -itis... (**on exam**)

Means that that part of the body is going through the inflammatory process

EX: appendicitis, pericarditis, neuritis, pancreatitis

Causes of Inflammation

•Direct physical damage

•Examples: cut, sprain

•Caustic chemicals

•Examples: acid, drain cleaner

•Ischemia (reduced blood flow) or infarction

•Allergic reactions

•Extremes of heat or cold

•Foreign bodies

•Examples: splinter, glass

•Infection

Steps of inflammation (**on exam**)

1. Transient Vasoconstriction

2a. Release of bradykinin from injured cells

2b. Activation of pain receptors by bradykinin

3. Mast cells and basophils release histamine

4. Capillary dilation

5. Increased blood flow

6. Capillary permeability

7a. Neutrophil and monocytes come to injury site

7b. Neutrophils

8. Neutrophils phagocytize bacteria

9. Macrophages leave bloodstream for phagocytosis of microbes

First step of inflammation (**on exam**)

Transient vasoconstriction

Body vasoconstricts because it doesn't know if the body is actively bleeding or not. The body automatically does this in case you are bleeding to stop it.

Step 2a of inflammation (**on exam**)

Release of bradykinin from injured cells

Bradykinin is a vasodilator and a mild diuretic (lowers BP)

(**Ding, DIng, DIng, DIng**)

It increases capillary permeability and is also involved in the mechanism of pain.

On Exam

During inflammation which WBC will arrive first

Neutrophils

Macrophages follow neutrophils is to make sure it gets it out of the body

On Exam

The steps of inflammation answer choice *This was stated during lecture, she will review the answer during tutoring*

vasoconstriction-->vasodilation-->hyperemia

What is vascular permeability?

the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells (lymphocytes on their way to the site of inflammation) in and out of the vessel.

Step 2b of inflammation

Activation of pain receptors of bradykinin

Bradykinin triggers pain receptors because the body wants you to pay attention

Step 3 of inflammation (**on exam**)

Mast cells and basophils release histamine (**must know**)

Histamine (*on exam*)

Produces the dilation of blood vessels, which increases permeability and lowers BP within an immune response

Central role as a mediatory of itching

Also causes bronchial constriction while vasodilating... can be very dangerous if uncontrolled

Step 4 of Inflammation

Capillary dilation (bradykinin and histamine)

Step 5 of inflammation (*on exam*)

Increased blood flow (hyperemia)

Step 6 of Inflammation

Capillary permeability

- Fluid leaks out and we get edema

Neutrophil (step 7a of inflammation) (**on exam**)

The first cells to arrive on the scene when we experience a bacterial infection

They are a type of WBC.

Is a phagocyte

Is the primary phagocyte that arrives early at the site of inflammation, usually within 90 min of injury

On Exam

If you are working in the ER and the patient has a reaction and you suspect they have an infection. What lab values are the most important to look at?

WBC, specifically neutrophils. The body produces more neutrophils to fight off the infection

What are the main types of phagocytes

a. Monocytes

b. macrophages

c. neutrophils,

d. tissue dendritic cells, and

e. mast cells

Step 7b of inflammation (neutrophils)

Able to generate oxygen (hydrogen peroxide) and nitrogen products (nitric oxide [NO]) that assist in destroying the engulfed debris

The neutrophil count in the blood often increases (**on exam**) greatly during an inflammatory process, especially with bacterial infections.... It requires an increase in circulating WBCs, a condition called **leukocytosis**) which is frequently elevated with bacterial infections and tissue injury

Test Question- Patient Scenario

The patient is really sick and the WBC count is really high. What does the patient have?

Answer: Leukocytosis

Monocytes

A type of leukocyte, or WBC

Adaptive immunity is an immunity that occurs after exposure to an antigen either from a pathogen or a vaccination (activated when the innate immune response is insufficient)

This part of the immune system is activated when the innate immune response is insufficient to control an infection.

Macrophages (Step 9 of inflammation) (**very important**)

Special cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms

Step 8 Inflammation

Neutrophils phagocytize bacteria

Adaptive immunity is what type of defense?

Third line defense]

NOT INNATE

Phagocytosis (step 9 of inflammation)

The process by which certain living cells called phagocytes ingest or engulf other cells or particles

Phagosome (step 9 of inflammation)

A vesicle formed around a particle engulfed by a phagocyte via phagocytosis

*What does vascular permeability lead to?*

Edema

Proteins leak out... protein loss... decreased osmotic pressure, increases interstitial osmotic pressure (intravascular-->intracellular space)

Fluid fills up in the third spacing

Exam Question

What is the cause of edema?

It is due to vascular permeability

Vascular changes with inflammation

Begin soon after injury and are characterized by vasodilation, changes in blood flow, increased vascular permeability, and leakage of fluid into the extravascular tissues.

What changes blood flow?

-Vasodilation

**Vascular changes when tissue is first injured**

The small blood vessels in the damaged area constrict momentarily (vasoconstriction).

Following this transient event, which is believed to be of little importance to the inflammatory response, the blood vessels dilate which increases blood flow to the area

Erythema (*on exam*)

Redness caused by congestion in the area after vasodilation and warmth associated with acute inflammation

Difference between neutrophils and macrophages

Neutrophil is a type of )(a) WBC, (b) granulocyte, and (c) phagocyte =Inflammatory Response

Neutrophils supplement macrophages with molecules that enhance macrophage antimicrobial capacities

Neutrophils transfer to macrophages intracellular pathogens

(**on test**) neutrophils show up first and macrophages follow

Cortisol effect on the immune system (**on exam**)

*Ding, Ding, Ding**

a. Primary stress hormone

Suppresses the immune system by suppressing the Th-1 cell activity (T1 helper cells) (part of the adaptive immune system-3rd line of defense)

Increases glucose

**Cardinal signs of Inflammation** (Will be on the exam in different ways) (**on exam**)

a. Heat

b. Redness (Rubor)

c. Swelling

d. Tenderness

e. Loss of function (make sure to choose this answer; students often miss this answer choice)

Pain

What are the chemical mediators that vasodilate and increase capillary permeability?(**Must know**) (**on exam**)

a. Histamine

b. prostaglandins

c. bradykinin (kinin)

Vascular changes (Vasodilation) that happen with inflammation

1. An immediate transient response (minor injury)(immediate injury=vasoconstrict)

2. An immediate, sustained response (Occurs with more serious injury and continues for several days and damages the vessels in the area)

3. A delayed hemodynamic response (involves an increase in capillary permeability that occurs 4-24 hours after injury)

What are the two types of leukocytes participate in the acute inflammatory response?** (**on exam**)

Granulocytes

Monocytes (the largest of the WBCs)

**What is a granulocyte? What are the three types of granulocytes?** (**on exam**)

Type of WBC that has small granules (that contain proteins). The granules help release peroxide onto the pathogen to kill them.

basophils, Eosinophils, Neutrophils,

Remember it has BEN)

**What are monocytes?** (**on exam**)

largest white blood cells

Monocytes can turn into macrophages

When are eosinophils triggered? (**on exam**)

alerted in allergic reactions or fighting off parasitic infection

Contain a protein that is highly toxic to large parasitic worms that cannot be phagocytized

Granules are red

Basophils (**on exam**)

Contain histamines

Blue granules

Come from your bone/bone marrow and circulates in the blood

**Essential for the inflammatory response**

HIGHER LEVELS ARE PRESENT DURING INFLAMMATION BECAUSE THEY CONTAIN HISTAMINE

Binding of IgE triggers release of histamine and vasoactive agents from the basophil granules

**Basophils and mast cells bind to what antibody?** (**on exam**)

Immunoglobulin E (This is an antibody) (immunoglobulin E helps fight off infections and allergic reactions and will triffer histamine

Mast cells

Derive from same hematopoietic stem cells (are the stem cells that give rise to other blood cells) and **do not develop until they leave the circulation and lodge in tissue sites** (whatever site they are sent to fo injury that is where they actually develop

A resident cell of connective tissue that contains many granules rich in histamine and heparin

Activation of mast cells mediates inflammatory responses such as hypersensitivity (overreaction) and allergic reactions.

Which of the following molecules will induce endothelial cell retraction?

A. Omega-3 fatty acids

B. Leukotrienes

C. Histamine

D. VCAM

C. Histamine

Rationale: Histamine is the primary activator of endothelial retraction and increased permeability of the vessels

**What is serous exudate?** (**on exam**)

Watery, thin and colorless exudate

**What is purulent exudate?** (**on exam**)

Thick, yellow-green (opaque), contains more leukocytes (WBCs), cell debris, and microorganisms (such as bacteria)

An abscess... localized pocket of purulent exudate in solid tissue. Inside of this abscess it will have fluid.

**What is hemorrhagic exudate?** (**on exam**)

present when blood vessels are damaged

Any time you see puss...

Rich with WBCs

Mild fever (pyrexia) leads to...

Release of pyrogens (destroy the cells of the body and systemically you will have an inflammatory response)

pyrogens: Released either from bacteria or viruses or from destroyed cells of the body, are capable of raising the thermostat and causing a rise in body temperature

Pyrogens are substances that can produce fever

Are fevers local or systemic? (**on exam**)

Systemic

Local injury DOES NOT CAUSE A FEVER

One of the systemic effects of inflammation is a? (**on exam**)

Fever

Systemic effects of inflammation

1. mild fever (pyrexia)

2. Malaise (feeling unwell)

3. Fatigue

4. Headache

5. Anorexia

Normal core body temperature (**on exam**)

97.0-99.5

Low grade fever temperature range

100.4-102.2

this is a low-grade fever

DO NOT CALL A DOCTOR ABOUT A LOW-GRADE FEVER

Nursing intervention: monitor and give Tylenol

*Do fever increase or decrease the body temperature?*

Fevers increase body temperature and the core body temperature is stored in the hypothalamus

What are exogenous pyrogens?

Induce host cells to produce fever-producing mediators called endogenous pyrogens (once fever is caused, we call them endogenous pyrogens)

What happens after phagocytic cells of the immune system engulf the bacterial products?

Pyrogenic cytokines are released into the bloodstream for transport to the hypothalamus, where they exert their actio.

These cytokines induce prostaglandin E2 (PGE2)

What induces fever in the body? (**on exam**)

Prostaglandin E2 (PGE2) acts on the brain (hypothalamus) to induce fever (it tells the body to reset the temperature)

The hypothalamus then initiates shivering and vasoconstriction that raise the body's core temperature to the new set point, and fever is established

What is endogenous pyrogens?

Fever-producing actions

Inflammatory mediators that produce other signs of inflammation such as leukocytosis (increased levels of leukocytes in the blood), anorexia, and malaise

What is the role of Prostaglandin E2 (PGE2)?(**on exam**)

This triggers the increase in the core body temperatures because during a fever, your body is hot.

Vasoconstriction happens

The course of a fever process