UTA 3366 Patho Exam #2

Impetigo

an eruption of blisters usually around nose & mouth that are itchy, crusty, and contagious

Innate Resistance

AKA "natural", defense mechanisms we are born with

1st Line Of Defense

the body's physical barriers which are immediate and non-specific

2nd Line Of Defense

inflammation, also immediate and non-specific

Acquired Immunity

AKA "adaptive", being able to resist certain diseases or conditions due to immunocyte involvement

Acquired Immunity is

delayed and specific

What is the First Line of Defense?

physical/mechanical and biochemical barrier and what breach them

What type of resistance is the First Line of Defense?

innate resistance

What are examples of the First Line of Defense?

skin and it's glands, and membranes/glands of body openings

Immunocytes are

lymphocytes (B-cells and T-cells)

Defense roles of the Skin and its glands

-protects more vulnerable areas underneath from simple hazards

-desquamation of skin(shedding of skin cells therefore bacteria too)

-glands secrete sweat which has antibacterial and antifungal properties

Antibacterial and antifungal properties of sweat

-attack cell walls of certain bacteria

-contribute to making the skin actually acidic making it inhospitable to most bacteria

Stressors that can breach the 1st Line of Defense

lacerations, abrasions, punctures, etc.

Eyes Defense Mechanism

-Tears: blinking causes lacrimal glands to spread tears over eyes=washing eye regularly

-Eyelashes

Stressors the can breach the Eye's Defense

-dry eye syndrome

-Sjorgren's syndrome

Dry Eye Syndrome

manufacturing of tears slows down' happens to some degree to almost everyone as they age

Sjorgren's Syndrome

autoimmune disease that dries up all lubricating fluids in the body

Respiratory System Defenses

-viscosity of mucus in nose

-hair traps bacteria

-cilia of cells sweep away foreign bodies

-cough reflex: foreign body inhaled reaches the carina>cough reflex stimulated

Stressors that can breach the Respiratory System Defenses

-cigarette smoking changes bronchial cells- no more cilia (metaplasia)

-cough reflex suppression such as in head injury or stroke

Gastrointestinal (GI) System Defenses

-saliva contains protective enzymes

-stomach: HCl destroys most microbes

-gag reflex/vomiting rids of injurious agents

-bowels (good gut flora and defecation)

Normal bowel are referred to as "good flora" because

they are microbes that live in harmony with us by keeping out malicious microbes by competing for food in the gut

Defecation

gets rid of injurious agents such as harmful bacteria

Stressors that can breach the Gastrointestinal (GI) System

-Sjorgren's: dry up saliva=less protection in mouth

-anything that changes bowel flora (ex: antibiotics)

Genitourinary System Defenses

-flow of urine washes away microbes

-vaginal secretions slightly acidic-kills bacteria

Stressors that can breach the Genitourinary System (GU) Defenses

-decreased urine flow (ex: kidney stones/failure)

-anything changing vaginal acidity such as douching

Expected manifestations of 2nd Line of Defense

Swelling, Heat, Erythema, and Pain (SHEP)

Because inflammation is an uncomfortable process it is often mistakenly though of as

an abnormal state

A normal inflammatory process is usually

acute and short-lived

Purpose of Inflammatory Response

to facilitate shifting of substances from blood into injured/irritated tissue

Inflammatory mediators

a subset of biochemical mediators- substances that act on the body in a variety of ways

2nd Line of Defense: Step 1 (way 1)

irritated/injured cells undergo disruption to metabolic pathway=loss of cell membrane integrity=leakage of fluid/other substances from all injured cells in the area

2nd Line of Defense: Step 1 (way 2)

Mast Cell Degranulation Occurs

specialized cell (Mast Cells) are stimulated by an irritant/injury and degranulate (leak) HLP (histamine, leukotriene, and prostaglandins)

2nd Line of Defense: Step 1 (way 3)

HLP causes vasodilation leading to the capillary becoming more permeable then "leaks" plasma containing neutrophils, clotting factors and fibrin

If MORE inflammation is needed, what comes the the affected area?

SYSTEMIC inflammatory mediators (acute phase reactants)

What are the Systemic Inflammatory Mediators?

Acute Phase Reactants (C-reactive protein, complement, circulating prostaglandins)

2nd Line of Defense: Step 2

neutrophils(phagocytic WBCs from the blood) and macrophages(phagocytic cells in the tissue) phagocytize any dirt, debris, dying tissue, and/or microbes they might find in the tissue area

Examples of Acute Phase Reactants (APR)

C-reactive protein (CRP), circulating prostaglandins, kinins, cytokines, complement, and more clotting elements like factors

If inflammation is occurring, there is always going to be a degree of

vasodilation and increased capillary permeability "leakiness"

Mast Cells

WBCs that are found in tissue instead of blood

Macrophages

-start life as circulating monocytes, and end up in the tissues as their home

-another type of

permanent" WBC of the tissue

-phagocytize microbes and other duties

Neutrophils

circulating phagocytes- kill microorganisms in blood and tissue

Lymphocytes

T-lymphocytes and B-lymphocytes; AKA the immunocytes

Exudate

combination of plasma, phagocytes, dead tissue cells, bacteria, fibrin, etc.

Serous Exudate

little microbe involvement, clear gold color

Serosanguinous Exudate

serous exudate with some blood

Purulent Exudate

AKA pus, microbe and WBC involvement, thick and whitish/yellowish

2nd Line of Defense: Step 3

if bacteria, viruses, or other microbes are a part of the serous exudate, macrophages will have phagocytized and processed them and now need help from the 3rd line of defense (the lymphocytes) to help kill the microbes but also create memory of the microbe

To involve the lymphocytes, the macrophages will

-secrete chemotactic substances to "call immunocytes (usually T cell/CD4 cell lymphocytes) to come to the are via the bloodstream

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

Chemotactic substances

biochemical mediators that summon OTHER substances to a certain area, or to increase in amount

2nd Line of Defense: Step 4

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

Degranulation

breaking apart of mast cells with spillage of granules of biochemical mediators into tissue

Granulating

tissue-pink, healthy, healing tissue

Granuloma

a hunk of tissue that has been chronically inflamed and is now essentially just scar tissue

The inflammatory response can be either

local or systemic

Local External Inflammatory Response Example

laceration or abrasion to skin

Local Internal Inflammatory Response Example: Appendicitis

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

Local Internal Inflammatory Response Example: Pleuritis

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

Local Internal Inflammatory Response Example: Thyroiditis

thyroid is inflamed because of an autoimmune attack

When tissues get irritated/injured, local cells leak and mast cell

degranulate biochemical mediators (Histamine, Leukotriene, and Prostaglandins)

HLP causes capillaries to

vasodilate and "LEAK"

Capillaries vasodilating and leaking allows phagocytes (mostly neutrophils) and coagulatory substances to

leak out and reach the injured area of tissue to help begin the healing process

Normal Systemic Inflammatory Response

same as local, but without a specific focus

S&S of Systemic Inflammation

-malaise, aches, and pains

-fever (from response to increased prostaglandins & acute phase reactants)

Purpose of Fever

has beneficial effect of directly killing some microorganisms but can also have deleterious effects

Deleterious effects of fevers

-can dilate blood vessels too much resulting in low blood pressure

-increases metabolic rate which may cause decompensation in very ill, debilitates, and/or elderly patients

Typical Systemic Inflammation Lab Tests

-CBC shows increased WBCs (leukocytosis)

-usually most increased is neutrophils (neutrophilia)

Lab Report showing Leukocytosis/Neutrophilia

total WBCs count= 15,000 K/ul (norm~5-10,000)

percentage of neutrophils=88%

(norm~50-75%)

Serum CRP will often be elevated during systemic inflammation because

it is an acute phase reactant (fuel on fire)

Anyone with not enough inflammation will be

extra susceptible to infections

Examples of "Not enough" inflammation include

defects in phagocytic functions and complement deficiencies

The 2 types of defects in phagocytic functions are

quantitative and qualitative

Quantitative defect in phagocytic functions (example from chemotherapy)

leukopenia (deficiency in WBCs) and neutropenia (deficiency in neutrophils)

Quantitative defect in phagocytic functions

-stem from genetic defect in synthesis of complement proteins

-pt's who have defects in these problems have problems that are very similar to those seen in pt's with antibody deficiencies (will be extra susceptible to infections)

Examples of inflammation going into overdrive (too much inflammation)

-SIRS

-Sepsis

-Septic shock

-chronic inflammation disorders

Shock

low BP that causes S&S; usually lower than 80 or 90 systolic

Systemic Inflammatory Response Syndrome (SIRS)

-occurs when normal systemic inflammatory response goes into overdrive

-contributes to widespread impaired tissue function and organ damage

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

-unexplained change in mental status (confusion, not as awake/alert)

-fever of more than 100.4

-increased heart rate

-increased respiratory rate

-abnormal white blood cell count

Sepsis

known/suspected infection+SIRS

Septic Shock

sepsis+low blood pressure

high levels of systemic inflammatory mediators trigger widespread extreme vasodilation> floppy arterial tone (vasomotor tone)>blood pools in periphery instead of circulating>low blood volume reduced amount of O2 being brought to tissues as well as decreasing BP

S&S of Septic Shock

-SIRS: change in mental status, fever, increased heart rate, increased respiratory rate, abnormal white blood cells

+

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

Chronic Inflammation

lasts weeks or longer, regardless of cause

Histamines, Leukotrienes, & Prostaglandins contribute to

vasodilation & increased vascular permeability = SHEP

Systemic Mediators Response

-help further lysis of bacteria

-enhance opsonization (identify and destroy) of bacteria

-attract more neutrophils as needed

-activate coagulation cascade so that clots can form and fibrin mesh can be established at site of injury

-contribute to vasodilation and permeability of blood vessels

-cause more pain

-help to attract lymphocytes cells as needed (CD 4 cells specifically since they are introducer cells)

3rd LOD Primary Immune Response

Initial exposure to microbe.

-CD4 acts as introductory cells

-CD4 accepts phagocytized remnants of antigen from macrophages and accept remnants

-CD4 displays antigen remnants on its cell membrane and decides what is the best response to deal with this particular pathogen (cell-mediated T cell response or humoral B cell response)

3rd LOD Secondary Response

Much more rapid and effective than primary response because they have immunity to antigen now

-cell mediated (T-cell): if same virus invades body, antigen-specific memory cells will immediately recognize it and very quickly send CD8 cells to area of invasion and kill it

-humoral (B-cell): if same bacteria invades again, the antigen specific B cells will immediately recognize it & differentiate into plasma cells which very quickly send out appropriate antibodies to area of invasion and destroy bacteria

MOA of non-medicinal interventions for inflammation: Protected Ice

cold numbs pain, coolness vasoconstricts the blood vessels of the area, this swelling & pain

MOA of medicinal therapeutics: Antiinflammatoriees

suppress the effects of prostaglandins (which works well in suppressing inflammation but can result in side effects)

What are the two types of anti-inflammatory drugs?

Steroids and NSAIDS (non-steroidal anti-inflammatory drugs)

Where are prostaglandins (PGs) created in the body?

most cells

Prostaglandins (PGs) are created in a series of steps called the

Arachidonic Pathway

What are the 2 general categories of Prostaglandins?

Protective or proinflammatory

Proinflammatory Prostaglandins

stimulate further inflammation

How do pro-inflammatory PGs stimulate further inflammation?

by increasing vascular permeability and inducing fever & pain

Most side effects due to inflammatory drugs are because what type of prostaglandin being suppressed?

protective prostaglandins

What would be the ideal effect of anti inflammatory drugs?

to be specific and suppress the proinflammatory prostaglandins ONLY

Arachidonic Pathway- "Birth Pathway" of Prostaglandins

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

What is the enzyme that catalyzes the creation of arachidonic acid from the phospholipids of the cell membrane?

phospholipases

Where in the arachidonic pathway do steroids work?

in the cell membrane by suppressing the phospholipase enzyme

What is the most common naturally occurring steroid?

cortisol

Synthetic examples of drugs based on the structure of cortisol

prednisone & solumedrol