UTA Pathophysiology Exam 2- NURS 3366

innate (natural) resistance

defense mechanisms we are born with

1st line: physical barriers that are immediate and non-specific

2nd line: inflammation, which is immediate and non-specific

(can also relate to our species, like we are naturally resistant to dog/cat specific diseases)

acquired (adaptive immunity)

3rd line of defense

-immunocyte (lymphocytes, B and T cells) involvement, this response is delayed and specific

-acquired through previous exposure to infections and other foreign agents

Neutrophils

-part of innate immunity

-primary phagocyte that arrives early at the site of inflammation (usually with in 90 minutes of the injury), in the blood count they will increase in number during the inflammatory process, especially with bacterial infections

-have a life span of 10 hours, so they will need to be replaced

Eosinophils

-part of innate immunity

-circulate in the blood and are recruited to tissues, similar to neutrophils

Macrophages

-part of innate immunity

-engulf larger and greater quantities of foreign material than the neutrophils,

-they live longer and signal the process of immunity to help resolve the inflammatory process and contribute to initiation of the healing process

Basophils

blood granulocytes with structural and functional similarities to mast cells of the connective tissue

first line of defense

physical/mechanical and biochemical barriers

-part of innate resistance

-includes skin and its glands, and membraces/glands of body openings

-responds immediate and non-specific

if stressor breaches the first line, 2nd and 3rd come into play

skin and its glands defense system

part of our first line of defense

-covering that protects us from heat, cold, environmental hazards

-the skin does desquamation (shredding of skin cells = bacteria sheds too)

-glands secrete sweat, which has antibacterial and antifungal properties

what are stressors that can breach the skin and its glands?

lacerations, abrasions, punctures, etc.

why does the desquamation of skin help us?

shedding of skin cells = bacteria sheds too

why does sweating help our immune system?

sweat has antibacterial and antifungal properties

-the chemical that sweat is made of can attack cell walls of certain bacteria

-it also helps make the skin acidic, which makes it inhospitable to most bacteria

membranes/glands of body openings (EYE'S DEFENSE)

part of the first line of defense

-tears: blinking causes lacrimal glands to spread tears over eyes & the tears drain into lacrimal ducts, washing the eye regularly

-eyelashes

what are stressors that can breach the eye's defense?

Dry Eye Syndrome- manufacturing of tears slows down, happens to some degree to almost everyone as they age

Sjogren's Syndrome- autoimmune disease that dries up all lubricating fluids in the body (mucus membranes can be dried)

membranes/glands of body openings (RESPIRATORY SYSTEM DEFENSES)

part of first line of defense

-viscosity of mucus (thick) in nose plus hair traps bacteria, same with wax and hair in the ears

-cilia of cells in bronchi can sweep away foreign bodies

-cough reflex: if a foreign body is inhaled and reaches the carina (which is where the right and left lung split), then cough reflex is stimulated

what are stressors that can breach the respiratory system's defenses?

cigarette smoking: changes bronchial cells, no more cilia (metaplasia)

cough reflex suppression such as in head injury or stroke

membranes/glands of body openings (GI SYSTEM DEFENSES)

part of first line of defense

-saliva: contains protective enzymes

-stomach: HCL destroys most microbes

-gag reflex/vomiting: gets rid of injurious agents like harmful bacteria

-the bowels have many good flora, microbes that keep out malicious microbes by competing for food

-defecation: gets rid of injurious agents like harmful bacteria

what are stressors that can breach the GI system defenses?

-Sjogren's also, because it dries up salvia and that equals less protection in the mouth

-anything that changes the bowel flora can leave us open to invading microbes (ex. of what might change the bowel flora is antibiotics)

membranes/glands of body openings (GENITOURINARY/GU SYSTEM DEFENSES)

part of first line of defense

-flow of urine washes away microbes (better in men usually, because they have a longer urethra)

-vaginal secretions: slightly acidic which kills bacteria

what are stressors that can breach the GU system?

-decreased urine flow, as in kidney stones or kidney failure

-anything that vaginal acidity, like harsh soaps or douching

second line of defense (normal inflammation process)

NORMAL inflammatory process

-inflammation is a state of INNATE defense characterized by being immediate and nonspecific AND

-expected manifestations such as a certain ("normal") degree of swelling, heat, erythema (redness) and pain

^SHEP

inflammation helps us defend against stressors, begins the healing process, AND it calls in the 3rd line of defense as needed

examples of normal inflammation

skin is breached by a cut from a knife -> area becomes red and sore as normal inflammation takes place -> immediately, certain processes take place which result in clot formation to stop bleeding -> fibrin components are weaved together to form a scab to seal the breach -> eventually, it becomes less painful as it heals

why is inflammation mistaken as abnormal?

because it is uncomfortable/painful

what is considered abnormal inflammation?

when it is out of control, occurs inappropriately, and/or becomes chronic and lasts longer than 2 weeks

What is the purpose of the inflammatory response?

to facilitate shifting of substances from blood into injured/irritated tissues to:

-clean up the area, begin the clotting process, and ultimately promote healing

-stimulate and enhance immunocyte response/3rd line of defense as needed

components of the inflammatory response (Step 1)

step 1: irritation/injury of tissue triggers same response anywhere in your body -> stimulates "leakiness" in three ways

what is the 1st way "leakiness" is stimulated by the inflammatory response?

irritated/injured cells that make up the tissue undergo disruption to metabolic pathway, that leads to loss of cell membrane integrity and leakage of fluid and other substances

then, what is the 2nd way "leakiness" is stimulated by the inflammatory response?

after the fluid is leaked by the injured cells...

MAST CELLS are nearby, and when the intracellular substances hit the mast cell it degranulates (which means they will leak granules)

-granules are local inflammatory mediators called histamine (H), leukotrienes (L), and local prostaglandins (P)

after HLP is leaked, what is the 3rd way "leakiness" is stimulated by the inflammatory response?

the HLP causes the local capillaries to vasodilate and "relax", which makes the capillary become more permeable and then leaks plasma into the tissue space

(this leaked plasma contains neutrophils, clotting factors, and fibrin)

What happens if it is a large inflammation and the local inflammatory mediators (HLP) can't solve the problem?

if more inflammation is needed, the neutrophils can call in the SYSTEMIC inflammatory mediators (AKA, acute phase reactants) come to the area via the bloodstream

examples are

-CRP (C-reactive protein)

-complement

-circulating prostaglandins (&many others)

what does the leaked plasma from the capillaries contain in the inflammatory response?

neutrophils, clotting factors, and fibrin

what are the granules that the mast cell leaks?

histamine, leukotrienes, and prostaglandins

components of the inflammatory response (Step 2)

(the leaked plasma contains neutrophils)

-Neutrophils (phagocytic WBCs from the blood)

AND

-Macrophages (phagocytic WBCs in the tissue)

WILL BOTH

-Phagocytize ("eat" & destroy) any dirt, debris, dying tissue, and/or microbes they might find in the tissue area

What is the result of the neutrophils and macrophages eating?

-the combination of plasma, phagocytes, dead tissue cells,bacteria, fibrin, etc, results in a thick fluid called *exudate ("inflammation soup")*

-depending on the problem, the exudate can have different colors (serous, serosanguinous, purulent)

What is the exudate called, and what is the color, when there is little microbe involvement?

-serous exudate

-clear gold color

What is the exudate called when there is blood involved?

-serosanguinous exudate

-light red color

What is the exudate called, and what is the color, when there is more microbe & WBC involvement (an infection)?

-purulent exudate (pus)

-thick, cloudy, and whitish or yellowish color

components of the inflammatory response (Step 3)

if bacteria, viruses, or other microbes are a part of the "mix", macrophages will have phagocytized & processed them and now need help from the 3rd line of defense

(the lymphocytes)

-will help to kill the microbes,

-also create memory (immunity) of the microbe

How do the macrophages involve the lymphocytes?

-secrete chemotactic substances (cytokine hormones) to “call” immunocytes (T cell/CD4 lymphocytes) to come to the area via the bloodstream

-display remnants of the microbes on their cell membranes as a guide to the T-lymphocytes

(“this is our enemy... now create some more defenses.”)

components of the inflammatory response (Step 4)

clotting factors, platelets, and fibrin come together in various ways in the area to create healing, granulating tissue

What is the difference between degranulation and granulating tissue?

Degranulation = When stimulated by an irritant or injury, the mast cell will degranulate—that is, “leak” chemical “granules” --these are local inflammatory mediators called, histamine, leukotrienes and prostaglandins (HLP)

Granulating tissue = Pink, healthy, HEALING tissue. The Last Step is when the Clotting Factors, Platelets and Fibrin come together to create healing – Granulating Tissue.

to review, what S&S and steps happen in ALL inflammation circumstances, no matter where it is located?

-swelling, heat, erythema & pain (SHEP)

-ALL the steps and components of the inflammation process will happen one way or another

Cardinal signs of inflammation are...

1. Redness

2. Swelling

3. Heat

4. Pain

5. Loss of function

inflammatory response can be...

-local (either local externally or local internally)

or

-systemic

example of local external inflammation

laceration or abrasion to skin, something you can see

examples of local internal inflammation

-appendicitis

-pleuritis

-thyroiditis

How are inflammatory conditions commonly named?

by adding the suffix "-itis"

appendicitis (local internal inflammation)

appendix gets irritated by a piece of food or microbe→ normal inflammation responds to the irritation→ appendicitis

(appendicitis becomes a disease process, because it is ultimately harmful to the body, but the initial inflammation was a normal defense of the body)

pleuritis (local internal inflammation)

inflammation of pleura when irritated by, for example, a lung cancer cell

-we will have leaking in the pleural space and that will cause issues for the patient

thyroiditis (local internal inflammation)

thyroid is inflamed because of autoimmune attack

NORMAL systemic inflammatory response

basically the same as local but without specific focus/area

-happens when the body needs the extra help system wide, like more leukocytes (leukocytosis) and more acute phase reactants (causing fever)

examples of normal systemic inflammatory response

1) a localized injury with infection of the big toe → local inflammation is initiated →local inflammatory mediators activate a systemic inflammatory response.

2) a localized infection of the bladder → local inflammation begins→ the microbe or the microbes toxins enter the bloodstream (bacteremia) → activates a systemic inflammatory response (cast of characters in the inflammatory mix: histamine,prostaglandin, leukotrienes, PLUS acute phase reactants such as CRP, large numbers of WBC's).

3) a traumatic injury occurs (car accident) → local inflammation is initiated → local inflammatory mediators activate a systemic inflammatory response.

S&S of systemic inflammation

-malaise, aches & pains

-fever

-lab tests like CBC will show increased WBCs - leukocytosis

Why does a fever happen, and what is it's purpose?

-happens from response to increased prostaglandins & acute phase reactants

-purpose of fever: has beneficial effect of directly killing some microorganisms

What can be some bad effects of a fever?

1) fever can dilate blood vessels→ too much vasodilation = low blood pressure

2) also, fever increases metabolic rate→ may cause decompensation in very ill, debilitated, and/or elderly patients

What would the lab tests show for systemic inflammation?

CBC (complete blood cell count) will show increased WBCs – leukocytosis

Why? Because

(1) leukocytes (WBCs) increase in number as they are “summoned” to the areas of inflammation

(2) The specific type of WBC that is usually most increased is neutrophils→ neutrophilia

(EX of lab report showing leukocytosis and neutrophilia:(1) total WBCs count = 15,000 K/ul (norm~5-10,000)

2) percentage of neutrophils = 88% (norm~50-75%))

serum CRP (C-reactive protein) will often be elevated because it is an acute phase reactant

Neutrophilia

elevated number of neutrophils in the bloodstream, as caused by systemic inflammation

2 different abnormalities of inflammation

"not enough" inflammation

"too much" inflammation

what will to people that have "not enough" inflammation?

they will be extra susceptible to infections

a couple of causes for "not enough" inflammation

-defect in phagocytic functions

-complement deficiencies

quantitative defect (defect in phagocytic functions)

1) leukopenia deficiency in WBCs

2) specific deficiency in neutrophils- neutropenia

example- from chemotherapy

qualitative defects (defect in phagocytic functions)

1) chemotactic defects—won’t respond appropriately when "summoned."

2) impaired function; ex—phagocytes damaged by diabetes mellitus have decreased ability to fight microbes

complement deficiencies

-these are a group of disorders that stem from a genetic defect in synthesis of complement proteins

-patients who have defects in these have problems that are very similar to those seen in patients with antibody deficiencies— they will be extra susceptible to infections

-these patients have issues with systemic inflammation, which means they might not have enough inflammation to fight off what is needed

complement/complement system (normal)

-complement: one of the acute phase reactants of inflammation

-the complement system: is a powerful effector mechanism of both innate and adaptive immunity that allows the body to localize infections and destroy invading microorganisms

"too much" inflammation examples

inflammation goes into "overdrive" and/or becomes chronic

-SIRS

-sepsis

-septic shock

-chronic inflammation disorders

SIRS (systemic inflammatory response syndrome)

-occurs when a normal systemic inflammatory response goes into overdrive (the normal "braking" system of the inflammatory process does not occur)

-instead, widespread systemic inflammation occurs in the entire body, not just in the original injured or inflamed ara

-this excessive systemic inflammation contributes to widespread impaired tissue function and organ damage

example of SIRS (big toe example)

localized infection in big toe -> local inflammation is initiated -> local inflammatory mediators activate a systemic response -> instead of healing, systemic inflammation goes into overdrive -> SIRS -> widespread tissue/organ damage

SIRS is present when 2 (usually more) of the following S&S are present

1) unexplained change in mental status (confusion, not as awake and alert as normal)

2) fever of more than 100.4°F

3) increased heart rate

4) increased respiratory rate

5) abnormal white blood cell count (WBC)

What is the body's NORMAL temperature?

98.6 °F

What would be a nurse's reaction of SIRS?

a nurse would know to monitor the patient as SIRS is a sign of caution, if SIRS occurs with an infection then you have issues (sepsis)

Sepsis

occurs when there is a known or suspected infection AND the person has SIRS

Sepsis = SIRS + infection

Why are nurse's key in the early recognition of S&S of SIRS and Sepsis?

-suspect sepsis and “save lives”

-mortality (death of a patient) increases by 10% every hour that treatment is delayed.

Why? Because treatment, within the first hour of sepsis S&S, prevents septic shock

Septic Shock

-occurs when sepsis (infection + SIRS) is complicated by low blood pressure

-“shock”: low BP that causes S&S = poor tissue oxygenation

-deadly for many patients

Why do patients die from septic shock?

high levels of systemic inflammatory mediators trigger widespread, extreme vasodilation

=

-no arterial vessel “tone” (which means good tension) → arteries become too relaxed, “floppy”→ blood pools in periphery instead of being part of circulation

→ eventually low blood volume reduces amount of O2 being brought to tissues as well as decreasing BP

S&S of septic shock

2) SIRS S&S

-change in mental status, fever

-increased heart rate

-increased resp rate

-abnormal white blood cells (WBCs)

2) low BP

-Low BP causes ischemia to organs so patient can have renal failure, respiratory failure, heart failure or death

Therapeutics for inflammation

-non-medicinal interventions

-medicinal therapeutics

non-medicinal interventions for inflammation

putting protected ice on the area of swelling

-cold numbs pain

-coolness vasoconstricts the blood vessels of the area, thus diminishing swelling & pain. (heat is the opposite—it vasodilates)

medicinal interventions for inflammation

anti-inflammatory medications

-suppress the effects of prostaglandins (can result in side effects, like suppressing the"protective" prostaglandin effect)

ex) STEROIDS, and NSAIDs "non-steroidal anti-inflammatory drugs"

prostaglandins (PGs)

-group of mediators that have a huge variety of functions

-created in the arachidonic pathway that takes place in most cell membranes

proinflammatory PGs -> contribute to vasodilation, capillary permeability, fever, pain

pro-protective PGs -> maintain

-appropriate clotting (Platelet)

-stomach lining (Gastric mucosa)

-good kidney function (Renal)

-appropriate vasomotor tone

-proper immunocyte function

What do most of side effects of anti-inflammatory drugs have to do with?

suppressing the “protective” prostaglandin effect as well as the “proinflammatory”

(ideal effect would be to be specific and suppress proinflammatory only)

arachidonic pathway

"birth pathway" of prostaglandins

-this is a process in the cell membranes of most cells which begins with generic phospholipids and ends with the creation of inflammatory mediators like prostaglandins and leukotrienes

what are the steps in how prostaglandins are made (the arachidonic pathway)?

1) the enzyme phospholipase interacts with the cell membrane's phospholipids -> makes arachidonic acid

2) the enzymes cyclooxygenase (COX 1 and COX 2) help make the 2 different kinds of prostaglandins, the protective (COX 1) and the pro-inflammatory (COX 2)

3) note that leukotrienes are also made here (that is the L in HLP), and they are also inflammatory mediators

What are the 2 types of prostaglandins and what are their functions?

proinflammatory: increase inflammatory response as needed

protective:

-have normal platelet clotting function (P)

-maintain the integrity of the gastric mucosa (G)

-promote healthy renal function (R)

-maintain appropriate vasomotor tone (V)

-maintain normal immunocyte function (I)

"Prostaglandins R Very Important"

What does "vasomotor" tone mean?

The ability of arteries to constrict when your body needs less blood supply to an area, and to dilate when your body needs more bloods supply. This responsiveness is a normal, healthy state of your arteries

Steroids are an anti-inflammatory, how do they work?

-they target the step in the arachidonic pathway where the phospholipase enzymes interact with the cell membrane phospholipids

-they suppress the phospholipase, prohibiting the creation of arachidonic acid

-they are non-specific and inhibit both the proinflammatory AND protective types of prostaglandins

What are examples of synthetic steroids (the drugs we take)?

prednisone & solumedrol

-based off the structure of cortisol, which is naturally occuring in our bodies

What is the most common naturally occurring steroid in our bodies?

cortisol

Why are steroids generally reserved for more severe inflammation?

-because they are the strongest and best anti-inflammatories since they work so high up in the arachidonic pathway (blocking both the prostaglandins and the leukotrienes)

-since they are the best, they can have a lot of side effects so we want to use them only when necessary

(acute back injuries, asthma, allergic reactions, bad rashes, lupus & other autoimmune diseases, etc.)

Why do steroids have bad side effects, and what are they?

because the prohibit the creation of the protective PGs as well as the pro-inflammatory PGs

-easier bleeding & bruising (no P help)

-risk for gastric or stomach ulcers (no G help)

-risk for kidney failure (no R help)

-risk for blood vessels to be vasoconstricted --> hypertension/HTN (no V help)

-higher risk for infections (no I help)

NSAIDS are an anti-inflammatory, how do they work?

-they suppress the COX enzymes, so they work at a lower part in the arachidonic pathway

-only suppress the prostaglandins, the leukotrienes are not affected

-they are not as powerful as steroids, nor do they have as bad of side effects

EX) aspirin, ibuprofen (Motrin), naproxen

3rd line of defense

normal immunocyte response (AKA acquired immunity)

involvement of immunocytes/lymphocytes

-T cells and B cells

this response is delayed (takes time to develop the ability to recognize and destroy microbes) and specific (immunocytes only respond fully to microbes that they recognize/have developed memory of)

What do T cells do, and what is the one we need to know?

T-lymphocytes (T cells) defend the body by direct attack against invading microbes

CD4 cells (aka, helper-T) act as "introductory" cells

-is the "general", directs the other types of lymphocytes

Where are T cells made, and where do they mature?

made in bone marrow, mature in thymus

How do B cells defend the body?

-once the B cell (B-lymphocyte) is called into action, it differentiates into plasma cells

-plasma cells create the antibodies to the microbe that has attacked the body (a particular set of antibodies now will always “remember” and “lay in waiting” for that specific microbe)

Antigens

blood molecule that can stimulate immunocyte reaction against them

-response to antigens that are foreign to our bodies is normal

-response to our own “self” antigens is abnormal

antigens are a "name tag" essentially, on the surface of the cells

Antibodies (IgG, IgE)

AKA- immunoglobulins

group of blood proteins that are made by the immune system in response to and defend against a specific antigen

Cell-Mediated Immunity

the T cell is "in charge" of developing immunity

-involves a primary response & a secondary response

Humoral Immunity

the B cell is "in charge" of developing immunity

-CD4 T cell is the "general" and organizes the B cell to take over

-B cell differentiate to plasma cells

-plasma cells create antibodies against specific antigens

involves a primary response & a secondary response

What is the primary response and the secondary response of both types of immunity?

primary response

-the first time the immunocyte/lymphocyte is introduced to the foreign invader, slower because takes time to "get to know" the foreign invader

secondary response

-if that same foreign invader comes back, this response is much quicker because the lymphocytes "remember" now and they can immediately defend against it

example of how the 1st, 2nd, and 3rd line of defense work together (B cell response)

Meningitis bacteria breach the mucous membranes (1st line of defense) in the nose and reach the meninges, causing inflammation. (2nd line of defense)

If local inflammation isn't enough, systemic inflammatory mediators are released.

1) Macrophages detect the microbe and call in CD4 T-cells, and displays the phagocytized remnant of the antigen on its membrane . (3rd line of defense)

2) The CD4 T-cell accepts and displays the antigen fragment and decides whether to use T-cells or B-cells.

3) Since the microbe is bacterial, B-cells are activated.

4) B-cells accept remnant from the T-cell, and differentiate into plasma cells and produce antibodies.

5) In the primary response, B-cells can’t fully defend, so the person will develop meningitis.

6) However, B-cells create "memory," so the person will be protected from future infections without symptoms.

The person has now developed antibodies and now has acquired immunity to the microbe

what are the other types of acquired immunity?

Active

-natural active

-artificial active

Passive

-natural passive

-artificial passive