Unit 2 Stuff

Acute inflammatory process sequences

* Congestion:
* Tissue begins with a normal histological appearance
* Blood capillaries will dilate (vasodilation or vasodilatation)
* Blood vessels becomes permeable (vascular permeability/venules and some arterioles)
* Exudation:
* Leakage of exudate (plasma leaks)
* Margination, rolling, adhesion of neutrophils (only in post-capillary venules or veins)
* Monocytes will follow 2-3 days later
* Transmigration through endothelium of vessel (diapedesis)
* Chemically attracted to areas outside of circulation (chemotaxis)
* PMN activation to release lysosomal substances
* Suppuration (pus/pyogenic)
* A protein-rich fluid containing white blood cells and cell debris
* Phagocytosis: the process whereby the WBC recognizes, attaches, engulfs, and destroys pathogen
* If there is not a need for extra leukocytes to fight an infection, this step may not occur
* Resolution
* The termination of the inflammatory response with the affected part returning to its normal state
* Could be complete resolution to normal histology
* Or scar tissue formation
* Or chronic inflammation (fibrosis)

3 PMNs (polymorphonuclear), i.e. the granulocytes

* Eosinophils
* Basophils
* Neutrophils

“Every boy needs (granulocytes) mom’s love (agranulocytes)”

The 3 PMNs are all…

Granulocytes

* Eosinophils
* Basophils
* Neutrophils

Agranulocytes

* Monocytes
* Lymphocytes

“Every boy needs (granulocytes) mom’s love (agranulocytes)”

Monocytes have an ___ in their nucleus

Indentation

Steps of the inflammatory response

1. Damaged tissues release histamines, increasing blood flow to the area
2. Histamines cause capillaries to leak, releasing phagocytes and clotting factors into the wound
3. Phagocytes engulf bacteria, dead cells, and cellular debris
4. Platelets move out of the capillary to seal the wounded area

Acute inflammatory process sequences (order)

Congestion → Exudation → Suppuration (pus/pyogenic) → Resolution

Acute inflammation

* Vessel dilation causes endothelial “gaps”
* Plasma leakage with protein “proteinaceous” is an exudate (more severe dilation)
* Leakage of water is transudate
* Extravasation of PMNs

Extravasation of PMNs

1. Margination


1. WBC normally flowing in center of lumen are attracted to the peripheral wall of the vessel


1. i.e. WBC are pressed up against the wall of the capillaries
2. Rolling


1. Roll, tumble, and heap on themselves
3. Adhesions


1. Adhere to vessel wall
4. Transmigration
5. Pathogens


1. WBC engulf

Exudate

* "The “ooze” coming out of wounds
* Fluid mixture of protein, leukocytes, and tissue debris
* Proportion of protein and inflammatory cells vary

Serous exudate

* Primarily fluid
* Seen in blisters (from friction) and pericarditis (inflammation of the heart)
* Clear
* Little protein
* Separates epidermis and dermis (so you don’t wanna pull on/break the blisters!!)

Serosanguineous exudate

* Clear
* Thin
* Pink

Sanguineous exudate

* Thin
* Watery
* Reddish

Purulent exudate

* Opaque
* Milky and green (pus)

Hemopurulent exudate

* Purulent
* Red tinged

Fibrinous exudate

* Rich in fibrinogen
* Coagulates and forms fibrin
* Produces a sticky film on surface of inflamed tissue

Catarrhal exudate

* Cloudy mucous
* Rhinorrhea (runny nose)

Adhesions exudate

Bands of fibrous tissue that bind adjacent tissue together

Hemorrhagic exudate

Increased red blood cells (red and thick)

Clinically, exudate is quantified as:

1. Non present: wound is dry
2. Scant: wound is moist with no evidence on bandage/dressing
3. Small/minimal: exudate covers less than 25% of bandage
4. Moderate: wound is wet with 25%-75% of exudate covering bandage
5. Large/copious: wound is seeping and covers over 75% of bandage

Inflammatory lesions: Abscess

* A circumscribed collection of pus
* Surrounded by a wall of inflammatory tissue

Inflammatory lesions: Ulcer

* An open sore or lesion of the skin or a mucous membrane accompanied by sloughing of inflamed necrotic tissue
* E.g. Decubitus ulcer (bed sore)

Inflammatory lesions: Furuncle

* A *specific* type of abscess
* An abscess or pyogenic (pus-producing) infection of a sweat gland or hair follicle

Inflammatory lesions: Carbuncle

* Several communicating boils (accumulation of dead and pus types of tissue, all tied together) with the production and discharge of pus and dead tissue
* Often located deep in the subcutaneous tissues of the neck or buttocks

Inflammatory lesions: Cellulitis or Phlegmon

* A diffuse, non-circumscribed, inflammatory infiltration of the tissues
* Subcutaneous forming pus pockets

Inflammatory lesions: Pustule

* A small, circumscribed elevation on the skin containing pus
* Pimple

Inflammatory lesions: Vesical

* A small, circumscribed elevation of the skin containing a thin, non-purulent fluid
* Blister

True culprit of inflammation (what causes all the nasty and pain)

PGs (prostoglandins)

In response in inflammation, you release

Arachidonic acid (AA)

Arachidonic acid (AA) produces

Prostaglandin G2

* Subsequently, Prostaglandin H2

Toll-like receptors (TLR’s)

* Present in the membrane of our immune cells
* Activated by pathogen-associated molecular patterns (PAMP’s)
* Macrophages recognize a PAMP on the outer membrane of gram-negative bacteria
* Activate and up-regulate NF-kB, a nuclear transcription factor that will activate an immune response and multiple immune mediators

NSAID

***Non-steroidal anti-inflammatory drugs*** (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down a high temperature

* E.g. Aspirin, Ibuprofen

Arachidonic acid (AA)

Acted upon by cyclooxygenase (COX) to produce a class of eicosanoids responsible for inflammatory responses

* These eicosanoids (AA derivative) include…
* Prostaglandin
* Thromboxanes
* Leukotrienes
* Lipoxins

Chemical mediators of inflammation

Mediators: chemical agents that intensify the inflammatory process

* Cell-derived mediators
* Mast cells: specialized connective tissue cells with granules filled with histamine, a vasodilator
* Histamine and serotonin: also in blood platelets
* Prostaglandins
* Leukotrienes: synthesized from arachidonic acid
* Mediators from blood plasma
* Bradykinin
* Complement
* Activated by antigen-antibody reaction
* Series of proteins that interact in a regular sequence

Prostaglandin (PGs)

Hormone-like substances found in almost every tissue of the body that can cause events as:

* Vasodilation or vasoconstriction of blood vessels
* Platelets to aggregate or disaggregate (stick or not stick)
* Induction of labor and delivery
* Pyretic (fever producer)
* Brochodilation and bronchosconstriction
* Hyperalgesic (increase pain)
* Most common prostaglandin in the body is PGE2, which is responsible for a majority of the list above

Infection

Inflammatory process caused by disease-producing organisms

Plasms cells come from

B cells

Infection: Cellulitis

Acute spreading of infection at any site

Infection: Abscess

Infection associated with breakdown of tissues, formation of pus

Infection: Septicemia

Overwhelming infection where pathogenic bacteria gain access to bloodstream

Infection: Pathogenic

Capable of producing disease

Infection: Virulence

A measure of severity of disease

Infection: Host

Affected individual or animal

Cancer is the ___ leading cause of death in the U.S.

2nd

Neoplasm

An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissues and persists in the same excessive manner after cessation of the stimuli which invoked the change

In situ

* Tumor remains in 1 location and does not invade basement membrane, which all cells are anchored to
* Abnormal cells are present but have not spread to nearby tissue

Infiltrating

Tumor invades basement membrane

Benign

Structure: Resemblance to normal cells (well differentiated)

Growth rate: Slow

* Organized growth

Mitoses: Few

* Uniform nuclei


* Low nuclear to cytoplasmic ration


* Minimal mitotic activity

Growth: Usually expansive

Growth duration: May stop growing

Encapsulation: Usually

* Lack of invading basement membrane

Metastasis: None

* No metastatic potential, cannot spread by invasion and only grow locally

Effect on host: Slight harm, due to location or complication

Malignant

Structure: Abnormal; less similarity to normal cells (anaplastic)

Growth rate: Rapid

* Disorganized growth

Mitoses: Relatively common

* Nuclear pleomorphism
* Nuclear hyperchromasia
* High nuclear to cytoplasmic ratio
* High mitotic activity and atypical

Growth: Invasive

* Invasion of basement membrane

Growth duration: Rarely stop growing

Encapsulation: Rarely (not well encapsulated, meaning it can spread elsewhere)

Metastasis: Frequent

* Invade neighboring tissues, enter blood vessels, and metastasize to different sites

Effect on host: Significant harm, due to invasion and metastasis

Pancoast Tumor

* Space occupying, benign lesion
* Cancers that start in the top part of the lung

Plasia

Formation, growth, and development

Reversible plasia: Hyperplasia

Increased number of cells

Reversible plasia: Hypertrophy

Increased size of cells

Reversible plasia: Metaplasia

Change in cells

Reversible plasia: Dysplasia

Disorderly proliferation

Irreversible plasia: Neoplasia

Abnormal new growth

Irreversible plasia: Anaplasia

Lack of differentiation

Irreversible plasia: Desmoplasia

Fibrous tissue formation in response to neoplasm

Irreversible plasia: Tumor

Originally meant any swelling, but now equated with neoplasia

Irreversible plasia: Metastasis

Growth at a distant site

Horner’s Syndrome

* Miosis: Constricted pupils


* Ptosis: Dropping of the eyelid
* Anhidrosis: Absence of sweating
* Due to a disruption in the sympathetic nerve supply

Epithelial tissue: Adenoma

* Glandular (live, kidney, bile duct)
* Can form from non-glandular epithelium (nephron epithelium)

Epithelial tissue: Pipilloma

Stratified squamous (HPV warts)

“oma”

Benign tumor

Connective (mesenchymal) and muscle:

* Fibroma
* Lipoma
* Chondroma
* Osteoma
* Hemangioma
* Leiomyoma (fibroids- smooth muscle)
* Rhabdomyoma (fibers of skeletal muscle)

Carcinoma

Involves epithelial tissue

* Most common: 85% of all tumors found in skin, large intestine, glands, stomach, lungs, prostate
* Metastasis: principally through lymph vessels and lymphatic route
* Subtypes:
* Adenocarcinoma: neoplasia of epithelial tissue that has a glandular origin
* Squamous cell carcinoma (skin)

SCC (Squamous cell carcinoma)

* Common form of skin cancer that develops in the squamous cells (in the epidermis) that make up the middle and outer layers of the skin
* Kind of where hair follicles are
* UV light exposure (e.g. tanning)
* Must excise it

BCC (Basal cell carcinoma)

Basal cells produce new skin cells as old ones die

Melanoma

* Melanoma is a disease in which malignant (cancer) cells form in melanocytes (cells that color the skin)
* Symptoms might include a new, unusual growth or a change in an existing mole

Signs and characteristics of moles/melanoma (ABCDEs)

* Asymmetry: When half the mole doesn’t match the other half
* Border: When the border (edge) of the mole are ragged or irregular
* Color: When the color of the mole varies throughout
* Diameter: If the mole’s diameter is larger than a pencil’s eraser
* Elevation: Changes in the height of the mole

Dyscrasia

An abnormal or disordered state of the body or of a bodily part (esp of the blood)

Sarcoma

* A tumor that occurs in the bones and soft tissues.
* Arising from connective tissues, such as fat, bone, cartilage, muscle

2 types of sarcoma

Bones and soft tissue

* Less common, but spreads more rapidly via hematogenous route
* Little differentiation; anaplasia (lack of form)
* Metastasis: bloodstream

Leukemia

* Neoplasm of blood cells
* Usually does not form solid tumors
* Instead, proliferates diffusely within bone marrow, overgrow, and crowd out normal blood-forming cells (e.g. red blood cells)
* Neoplastic cells spill over into the bloodstream, and large number of abnormal cells circulate in the peripheral blood

Ewing’s Sarcoma (ES)

* 2nd most common type of primary bone cancer
* Median age of 15 years
* Commonly seen in Caucasian male population
* Primarily seen on long bones of the lower extremity and pelvis
* Sx of pain, swelling, fever, weight loss, and fatigue
* MRI shows lesion in the diaphysis or metaphysis
* Periosteum shows an “onion skin” appearance
* Primary metastatic site is lungs
* CT of lungs to rule out mets
* Bone aspiration needle bx is performed to confirm dx
* Should be performed by trained surgical oncologists to ensure the retrieval of the cancer cells are not seeded elsewhere
* 20-30% of patients that receive initial dx have mets to the lungs

Angiogenesis

Tap into blood supply and invade vessels

Localized

Cancer is limited to the place where it started, with no sign that it has spread

Regional

Cancer has spread to nearby lymph nodes, tissues, or organs

Distant

Cancer has spread to distant parts of the body

Unknown

There is not enough information to figure out the stage

How to determine the stage of cancer

T, N, M results

___ stages of cancer

4

Stage 0 cancer:

* Cancer in situ, which means “in place.”
* Stage 0 cancers are still located in the place they started and have not spread to nearby tissues
* This stage of cancer is often highly curable, usually by removing the entire tumor with surgery

Stage 1 cancer:

* This stage is usually a small cancer or tumor that has not grown deeply into nearby tissues
* It also has not spread to the lymph nodes or other parts of the body
* Early-stage cancer

Stage 2/3 cancer:

* Indicate larger cancers or tumors that have grown more deeply into nearby tissue
* They may have also spread to lymph nodes but not to other parts of the body

Stage 4 cancer:

* Cancer has spread to other organs or parts of the body
* May also be called advanced or metastatic cancer

Tumors derive blood supply from…

Tissues they invade

* Malignant tumors frequently induce new blood vessels to proliferate in adjacent normal tissues to supply the demands of the growing tumor
* Malignant tumor may outgrow its blood supply; the part of the tumor with the poorest blood supply undergoes necrosis
* Depending on the location of the tumor, the blood supply will be rich or poor

Non-specific diagnosis of tumors: laboratory procedures

* Examination of rectum and colon
* Vaginal examination and pap smear in women
* Examination of esophagus and stomach
* X-ray

Specific diagnosis of tumors: laboratory procedures

* Tumor-associated antigen tests (TAA):

Some cancers secrete substances that can be detected in the blood by lab tests

Specific diagnosis of tumors: laboratory procedures

* Abnormal smear:

Slides of abnormal cells shed from surface of tumors

Specific diagnosis of tumors: laboratory procedures

* Cytologic diagnosis:

From smears, needle aspiration, biopsy

Specific diagnosis of tumors: laboratory procedures

* Frozen section:

Slides prepared and stained for rapid histologic diagnosis

Specific diagnosis of tumors: laboratory procedures

* Carcinoembryonic antigen (CEA):

* Normally produced in the Gl tract or fetus and stops before birth
* Present in amounts related to size or tumor and its possible spread
* Produced by most malignant tumors or the colon, rectum, pancreas, breast

Specific diagnosis of tumors: laboratory procedures

* Alpha-fetoprotein (AFP)

* Normally produced by fetal liver tissue
* In adults, elevated in primary carcinoma of the liver (70% of liver cancers)

Specific diagnosis of tumors: laboratory procedures

* Human chorionic gonadotropin (HCG)

Normally produced by placenta; elevated in testicular carcinoma

Specific diagnosis of tumors: laboratory procedures

* Acid phosphatase (AP):

Normally produced by prostate epithelial cells, may be elevated in prostate cancer

Tumor grading (TMN system)

T: size and extent of the main tumor

* Main tumor is usually called the primary tumor

N: number of nearby lymph nodes that have cancer

M: whether the cancer has metastasized; this means that the cancer has spread from the primary tumor to other parts of the body

Primary tumor (T)

* TX:
* T0:
* T1, T2, T3, T4:

* TX: main tumor can’t be measured
* T0: main tumor can’t be found
* T1, T2, T3, T4: refers to the size and/or extent of the main tumor; the higher the number after the T, the large the tumor or the more it has grown into nearby tissues
* T’s may be further divided to provide more details (e.g. T3a and T3b)

Regional lymph nodes (N)

* NX:
* N0:
* N1:
* N2:
* N3:

* NX: lymph nodes cannot be assessed
* N0: no regional lymph node metastasis
* N1: regional lymph node metastasis present; at some sites, tumor spread to closest or small number of regional lymph nodes
* N2: tumor spread to an extent between N1 and N3
* N3: tumor spread to more distant or numerous regional lymph nodes

Distant metastasis (M)

* MX:
* M0:
* M1:

* MX: metastasis cannot be measured
* M0: cancer has not spread to other parts of the body
* M1: cancer has spread to other parts of the body