ch8 immune system + wound healing

what are the possible sources of disease? (5)

• genetic

• acquired

• multifactorial

• idiopathic

• latrogenic

what is a genetic disease? (2 types)

• congenital (present at birth)

• noncongenital (evidence later in life), e.g., cystic fibrosis

what does idiopathic disease mean?

origin of disease is not known

what does latrogenic disease means?

resulting from medical intervention, treatment, procedure or error

define signs

observable phenomena that can be verified

define symptoms

 factors verbalized by the patient and frequently noted by the chief complaint in the physician's history and physical examination

define outcome (in terms of disease)

referred to as the sequelae of disease

Possible outcomes: cure, remission, chronic disease, or death

define prognosis

 refers to the expected or usual outcome

how do cells become injured (4 main categories)

• Physical injury- burns, mechanical trauma

• Infection- microbial

• Deficiency- hypoxia, nutrients, genetic abnormalities

• Excess- toxins, nutrients, genetic abnormalities

what are the main 4 ways cells react to injury and disease?

• cellular accumulation

• abnormal cell growth or development

• cell degeneration or death (necrosis)

• inflammatory response

what do we mean by cellular accumulation?

Ex: fat in liver, pooling blood in hematoma, amyloid plaques in brain

what are the 5 different cellular alterations that may occur?

• atrophy

• hypertrophy

• hyperplasia

• metaplasia

• dysplasia

define atrophy and its common causes (several)

 results from a decrease in cell size

Common causes: decreased workload, loss of innervation, diminished blood supply, inadequate/deficient nutrition, loss of hormonal stimulation, aging

define hypertrophy

defined as an increase in cell size

Can be due to increased functional demand or hormonal stimulation

define hyperplasia

overall cell number increases

define metaplasia

occurs when disease or injury results in displacement of one cell type by another that may be less mature

examples:

Environmental toxins (e.g., air pollution) --> respiratory epithelial cells

Chronic inflammation - Barrett's esophagus from chronic gastric reflux

Vitamin A deficiency: urinary and respiratory epithelial cells

what 3 things must be true for an infection to be at play?

• Pathogen must be present

• Host must be susceptible to the infection

• Environment must be conducive to proliferation of pathogen

susceptibility to infection is influenced by what factors

age, gender, nutritional status, physical activity, hormones, and stress

what are the stages of infection (4)

• incubation

• prodomal

• acute

• recovery/covalescence

what is incubation stage

the time between entry of the microorganism and appearance of any clinical signs or symptoms.

what is prodromal stage

when the individual begins to experience the first, even vague, symptoms of infection

what is acute stage

peak of the infection; clear, strong signs of specific disease appear

what is recovery/convalescence stage

Immune system starts to win, symptoms fade, body returns to normal

what are the 2 types of cell death

necrosis and apoptosis

what is necrosis

refers to the cellular changes that occur during cell death (not normal)

define apoptosis

pattern of cell death genetically programmed, which allows for removal of cells in a systematic, orderly fashion

what things contribute to host resistance (what does you body have that helps resist infections)? (3 main)

• Intact skin and mucous membranes form physical and chemical barriers

• Body secretions such as saliva, tears, and gastric juices

• Effective immune system, inflammatory response, and absence of underlying disease

what are the central organs of the immune system

bone marrow and thymus

what are the peripheral organs of the immune system

spleen and lymphatic system, MALT, GALT, BALT

what are the functions of the immune system (3)

• Defends body from pathogens

• Actively promotes homeostasis

• Provides surveillance

what are the 4 basic requirements of the immune system?

• Specificity

• Diversity

• Adaptivity

• Ability to respond to new stimuli

what are the 2 types of immunity?

innate and acquired/adaptive

what is innate immunity

first line of defense --> nonspecific

• cellular response is inflammation

what is acquired/adaptive immunity

immune response that results from exposure to an antigen or immunoglobulin

recognize and respond to specific foreign material

what is an antigen

any substance that can bind to immune cell or antibodym

most antigens are ______; some can be ___________-

immunogens ; a piece of bacterium or virus or other cell

what are immunogens

substance that always triggers immune response 

immune cells are (main name)

WBC (leukocytes)

what are the type of immune cell categories?

• macrophage/monocyte

• neutrophils

• basophils

• eosinophils

• lymphocytes

what are macrophages/monocytes? (function)

• ingest and destroy bacterial, aged cells, and neoplastic cells in a process called phagocytosis

• They can break down antigens into small pieces that they “present” on their cell surface for other cells of the immune system to recognize and respond to—that is, they serve as antigen-presenting cells

what are polymorphonuclear leukocytes?

Neutrophils, eosinophils, and basophils

Act as the body's rapid responders to infection and inflammation

Neutrophils, eosinophils, and basophils are distinguished by

 the shape of the nucleus and the stains taken up by the granules

what are other cells that are derived from myeliod stem cells? (3)

Mast cells, dendritic cells, and Langerhans cells

what are mast cells?

release histamine and TNF-alpha when triggered due to innate immunity and allergic reactions

the lymphoid precursor differentiates into cells that make what system?

adaptive immune system

what are the 3 types of lymphocytes?

T cells, B cells, and natural killer cells

what are the type of T cells? (3)

helper T cells (CD4+), cytotoxic T cells (CD8+), and regulatory T cells

what is the function of B cells (main)

make antibodies to fight infection

types of antibodies?

IgG,  IgA, IgM, IgD, and IgE

what molecules can detect the difference between our cells and those of antigens and communicate it to other cells? (2 types)

Major histocompatibility complex (MHC) and human leukocyte antigens (HLA)

what do Major histocompatibility complex (MHC) and human leukocyte antigens (HLA) do?

• Play a role in susceptibility to some autoimmune and infectious disease

• How the detection of antigens (detect a cell different from our own) can be communicated to other cells

these molecules are on APC (antigen-presenting cells) like for example the macrophage that takes the antigen and presents it to helper T cell (macrophage is APC; MCH molecule is what selects the fragment and brings it to cell surface for T cell to read)

what are the 2 types of mediators that assist the immune system’s cells in their function?

cytokines and complement cascade

what is the complement cascade?

“complement immune response”

• The complement proteins are a system of proteins that are activated by other elements of the immune response and react in a tightly regulated cascade and are involved in destroying infected cells and some pathogens.

• Final product: membrane attack complex (MAC)--> lyses cells by making holes in target cells; triggers inflammation and phagocytosis

what are cytokines?

Small proteins or glycoproteins that are signal molecules that are produced by cells (primarily T cells and macrophages)

they are proteins produced in cells that, in small amounts, affect behavior of other cells

cytokine function?

affect behavior of other cells

The target cell may be activated, stimulated to proliferate, or stimulated to differ entiate into another cell.

ex: interleukin (IL-1, IL-6), tumor necrosis factor (TNF), interferon (INF)

how to cytokines work?

An inducing stimulus causes a cell to make a cytokine which binds to surface receptor on target cell. The result is altered biological activity in the target cell

cytokines work where?

Autocrine and paracrine effects; Cytokines aka "local hormones"

Rarely endocrine effects

what is the complement cascade?

a system of plasma proteins that react in tightly regulated cascades activated by antibodies or specific molecules found on pathogens

how does complementary cascade work?

• Plasma proteins that react to antibodies or pathogens in a tightly regulated cascade

• Final product: membrane attack complex (MAC)--> lyses cells by making holes in target cells; triggers inflammation and phagocytosis

what innate immunity?

first line of defense--> nonspecific, cellular response in inflammation

which cells are important for innate immune system? (4)

macrophages, monocytes, natural killer cells, and leukocytes (neutrophils)

these cells react how fast and to what?

React immediately with any antigen or in response to injury (nonspecific)

react with any antigen—→ they can thus react immediately

what is the response of innate immunity?

localized or acute systemic inflammation

what are the signs of imflammation?

Signs and symptoms are redness, warmth, swelling, and pain resulting from hyperemia (increased blood flow) and vascular permeability

how does inflammation occur (steps)

• A break in the skin introduces bacteria, which reproduce at the wound site. Activated resident macrophages engulf the pathogens and secrete cytokines and chemotaxins

• Activated mast cells release histamine which dilates local blood vessels and widens the capillary pores

• vasodilation increases blood delivery to injury site and increased permeability of pores leads to fluid accumulation —→ redness, heat, swelling, pain

• cytokines cause neutrophils and monocytes to stick to vessels and chemotaxins attract neutrophils and monocytes which squeeze between cells (diapedesis) and migrate to the site

• Monocytes enlarge into macrophages. Newly arriving macrophages and neutrophils engulf the pathogens and destroy them

what are the 3 types of inflammation?

• inflammation

• acute inflammatory response

• chronic inflammatory response

inflammation

• location

• response time

• responses (bodily)

• localized

• seconds to minutes

• redness, heat, swelling, pain

acute inflammatory response

• location

• response time

• responses (bodily)

• systemic

• hours to days

• fever, neutropenia, anorexia, fatigue; labs: increase WBC, CRP, fibrinogen, ESR

chronic inflammatory response

• location

• response time

• responses (bodily)

• systemic

• months to years

• increased CRP, fibrinogen, ESR, NF, IL-6, TNF-a

mediators of inflammation

nitric oxide function in inflammation

destroys toxic microbes

lactoferrin function in inflammation

secreted by neutrophils; bins to iron and prevents its use by invading bacteria

histamine function in inflammation

 increase blood flow and vascular permeability, allowing fluid an proteins to see from blood into interstitial spaces

ROS function in inflammation

toxic for microorganisms but also damage body tissues

interleukins and TNF function in inflammation

 pro inflammatory cytokines that help trigger blood clotting and T,B cell activation, lower BP, trigger fever, release of prostaglandins, decrease iron availability, and stimulate CRP release

CRP function in inflammation

acute phase protein that works to enhance phagocytosis by targeting bacterial cells for destruction; used as serum marker for inflammation

PGs function in inflammation

 increase vascular permeability and influence platelet aggregation

leukotrienes function in inflammation

prolong the response and has vasoactive properties

what are the 3 classes of drugs often used to combat inflammation?

steroids, NSAIDs, and COX-2 drugs

what are the function of steroid (for inflammation)

Interrupt formation of arachidonic acid, which is the precursor to many lipid mediators of inflammation—> reduce pain and swelling from inflammation

ex: prednisone

what are the function of NSAIDS

they are non-selective COX inhibitors (inhibit both COX-1 and COX-2 pathways) and stop the prostaglandin production from arachidonic acid

ex:  ibuprofen, aspirin, naproxen

what is the function of COX-2 inhibitor drugs?

Inhibit enzyme pathways for generation of prostaglandins but allow for COX-1 protection

ex: celecoxib (Celebrex)

how have we used nutrition for inflammation prevention

changes in micronutrients during inflammation (table)

• Increased:

  • Copper carrying protein (ceruloplasmin) increases which helps immune cells use copper to kill pathogens

  • Ferritin and hepcidin increases because iron production increases, and it traps it so that pathogens cannot use it

  • Thiamin increases because energy needs increase, and B1 is needed for citric acid cycle and ATP production

• Decreased:

  • Iron decreases because hepcidin traps it

  • Zinc is removed from blood and into liver and tissues to help make new cells

  • Selenium decreases because protein that makes it decreases in levels

  • Vit C is a antioxidant so it is used very quickly by WBC

  • Fat soluble vitamins decrease because liver stops making their carrier proteins

complications to inflammation and wound healing (3)

Dehiscence, adhesions, contractures

what is dehiscence

partial or total separation of previously closed wound edges

aka: wound reopens

what are adhesions

result when two previously unconnected tissues are abnormally joined together

what are contractures

permanent tightening, shortening, or thickening of skin, muscles, tendons, or joint capsules which severely restrict normal range of motion

ex: healed burns

define wound healing

Process by which structure and function are restored

what are the stages to wound healing?

• Inflammatory

• Proliferation

• Remodeling

inflammatory stage of wound healing: how long does this stage last?

• begins at the time of injury

• continues for about 4-6 days

inflammatory stage of wound healing: what happens in this stage?

• Coagulation cascade and fibrin clot formation control bleeding

• Vasodilation and increased capillary permeability occur

• Neutrophils phagocytize bacteria

• Macrophages remove debris and necrotic tissue and secrete growth factors

proliferation stage of wound healing: duration

• Begins about the 3rd to 5th day

• continues for 2-3 weeks

proliferation stage of wound healing: what occurs?

• Epithelial cells form a protective covering and framework over the wound

• Angiogenesis produce collagen and matrix protein, forming granulation tissue

• Collagen deposition and cross-linking begin to strengthen the wound

• Myofibroblasts induce wound contraction and the wound begins to close

remodeling stage of wound healing: duration

Begins about 2-3 weeks after injury and can continue for up to 2 years

remodeling stage of wound healing: what happens?

• Collagen maturation and stabilization occur

• Fibrous scar tissue matures (decreases in fibroblasts and vascularization) but skin and fascia never regain full strength

MNT for wound healing: kcals

• Function:

  • adequacy required to preserve muscle and maintain weight

• Reference intake (general; not for wound healing):

  •  NA

• Nutrition assessment reccs:

  • monitor weight closely for unexplained losses

• Recc intake (wound healing/deficiency noted):

  • goal of 30-35kcal/kg for those who are malnourished or at risk of malnutrition depending on the type of wound

• Additional notes:

  • Monitoring actual kcals received is essential

  • Kcal goals should be adjusted for ebb and flow phases of the hypermetabolic response, severity of wound, respond to healing, comorbidities, and other factors that affect metabolic rate

for wound healing, what are the nutrition assessment reccomendations to determine kcals

monitor weight closely for unexplained losses

recommended Kcal for wound healing

goal of 30-35kcal/kg for those who are malnourished or at risk of malnutrition depending on the type of wound

what should be monitored (for kcals)

Monitoring actual kcals received is essential