Pathology

it isia protective response, it attempts to eliminate the initial cause of cellular injury and necrotic cells, it is involved in the process of repair, and it has the potential to cause further harm. It has two components, Vascular and Cellular.

vasodilation and structural changes that result in increased permiablility

emigration of leukocytes to from the circulation to the point of injury.

stimuli - infectious, physical, chemical, immunologic, and necrotic agents. characteristics - short, exudation of fluids and protiens, emigration of WBC's, stereotypic pattern and platelets.

edema is excess interstitial or serous cavity fluid, and the other is fluid rich in leukocytes and cellular debris.

protein content. exudate has SG higher than 1.015

(it occurs in the venules) histamine, leukotrienes, etc.
(toxins, burns, chemicals in all vessels)

(in venules and capillaries) cytokines, IL-1, TNF, hypoxia

Leukocytes are swept against the vascular wall in post-cappilary venules due to flow dynamics and stick as they roll along. (because of selectins)

receptors on leukocytes (L-selectins) and endothelium (E-selectins)Histamine causes E-selectins to go to surface of cell so when a leukocyte rolls by, it binds to the L-selectins to slow it down so it can come out of circulation. They have a very low affinity

cell surface receptors that bind to the ECM & mediate intracellular signals. Define cell shape, motility, and cycle. Also aid in cell to cell attachments. They also transduce signals

migration of a leukocyte through a vessel wall at an intercellular junction.Mediated by PECAM-1

Locomotion along a chemical gradient. Can be endogenous or exogenous.

they cause the migration of WBC's and the activation of leukocytes. The leukocytes produce arachadonic acid metabolites. It also causes them to degranulate, secrete lysosomal enzymes and cause the modulation of adhesion molecules

Microbes, products of necrotic cells, and mediators.

recognition( by opsonins, or microbes or dead cells) and attachment, engulfment (triggered by binding of the Fc part of IgG with the opsonin), and degradation

oxygen dependant-dependent on NADPH and reactive oxygen species such as hydrogen peroxide.
oxygen independant- granule release

the products of the phagolysosome are released into the extracellular space and cause damage.

Neutropenia (low WBC count), adhesion, phagocytosis, migration, chemotaxis, and microbial activity

amplification, they are short lived, they are from the plasma and are produced locally, and they may target one or many types of cells

short half-lives. Inflammation triggers stop signals - switch from pro leukotrienes to anti lipoxins, TGF-beta is released from macrophages, Neural impulses that inhibit the production of TNF from macrophages

released by mast cells, basophils and platelets. Causes dilation of arterioles and increases vascular permiability (Gap formation)

IgE reactions (asthma), Anaphylactoxins (C3a and C3b) leukocyte proteins, cytokines IL-1 and IL-8

released from platelets when they aggregate

classical starts with an activated IgM or IgG molecule. C3a, C5a, and C4a become an anaphalactic toxin. C3b becomes opsoinin and is responsible for splitting C5.
C5a also becomes a chemotactic factor for granulocytes and monocytes, and activates the lipoxygenase pathway. C5b contiunes on the pathway

Fc portion of IgG and C3b, opsonins are binding enhancers for phagocytosis

short half life, proteolytic inactivation, binding of active components, and cell membrane associated molecules

increases vascular permiability by releasing bradykinins, causes smooth muscle contraction and blood vessel dilation and PAIN.

alternate binds to a cell starting at C3. Classical starts at C1 with an activated IgG or IgM.

Factor 12a from the clotting system

it increases vascular permiability.

causes vasodilation and inhibits platelet aggregagation

causes vaso constriction and promotes platelet aggregagation

causes vasoconstriction, bronchspasm (asthma) and vascular permiability

arachadonic acid

produced by mast cells and causes platelet aggregagation and release and bronchoconstriction, vasodilation, increased permiability, much more potent than histamine

fever, sleepy, less appetite, shock, neutrophilia

increased leukocyte adherance by stimulstting endothelial cells to produce adhesion molecules, PG1 synthesis, procoagulant activity, and decreased anticoagulent activity, and induces repair of damaged area

produced by endothelial cells, macrophages, and neurons. Causes vasodilation and inhibits platelet aggregagation. It is toxic for microbes!

prolonged acute inflammation, fungi, TB, foreign bodies, persistent infections, autoimmune diseases

tissue destruction and attempted healing by connective tissue (Scar formation), angiogenesis, and fibrosis

monocyte/macrophage (also see B and T cells, mast cells, eosinophils, and neutrophils)

at the sight of injury or inflammation

chronic infection where giant cells are formed. Can occur because of foriegn diesease or can happen spontaneously

thin fluid with few cells (blister)

large ammount of fibrin, leads to a scar

has dead cells and debris and WBC in the fluid (pus)

fever and leukocytosis (and a little bit of leukopenia as well)

labile - proliferating throughout life
quiescent - normally don't replicate, but can if needed to
nondividing - no proliferation after birth

stem cell division. Doesn't lead to the same thing can become something different with each replication

a change in stem cell differentiation from one cell type to another

cell replication, migration, differentiation, and synthesis if specialized proteins. (have pleiotropci effects) they target the function of protooncogenes

autocrine - stimulates same cell
paracrine - stimulates cells nearby
endocrine - into vessels to go elsewhere

receptors with (causes dimerization of the receptor and autophosphorylation) and without (recruit cytosolic kinases or activate other plathways to generate a 2nd messenger) intrinsic kinase activity, and G protein-linked receptors

cell surface, cytoplasm, in the nucleus

Ras activation and MAP-kinases. (also IP3 and PI3 pathways and phopholipase C)

control the entry and progression of the cell through the cell cycle. Cylcins also form complexes with the cyclin dependant kinases so they can perfom their function too.

DNA replication, Depolymerization of nuclear lamina, and formation of mitotic spindles

surveillance. If a critical transition occurs, the cell will stop proliferation and fix the problem, if the problem can't be fixed, the cell will undergo apoptosis

Uses the same receptor as Transforming Growth factor-alpha.

causes migration and proliferation of fibroblasts, smooth muscle cells, and monocytes

the basic (FGF-2) one induces angiogenesis (new blood vessel formation). It also plays a role in wound repair, development, and hematopoeisis

in lowel concentrations, it promotes growth by inducing the synthesis and secretion of PDGF. In high concentrations, it inhibits PDGF receptors, inhibiting growth.

angiogenesis

induces fibroblast chemotaxis and proliferation, that stimulates the synthesis of collagen and collagenase

disease present at birth, does not mean it is genetic (not all genetic diseases are congenital as well)

genome is the loss or gain of chromosomes, chromosomal is the rearrangement of genetic material

change in a single nucleotide thay may lead to achange in an amino acid.
conservsative- little or no change in function
nonconservative- big change in function

creates a stop codon

leads to an alteration in the reading frame of the DNA strand. (deletion or insertion of 1,2,etc, not 3)

amplification of a sequence of 3 nucleotides. The degree of amplification increases in gametogenesis

exact mutiple of 23 chromosomes.
not exact multiple of 23

% of individuals with an autosomal dominant gene that express the trait.

a single gene mutation may lead to many phenotrophic effects in one patient

variety of different problems from patient to patient with the same autosomal dominant disease

manifested in heterozygous state. one parent affected. Both sexes effected equally and both can transmit. Each child has 50% chance of getting it if one parent is effected. Onset can be delayed

proteins involved in the regulation of complex metabolic pathways (membrane receptors and transport proteins), and key structural proteins.

usually homozygous. both parents posess gene, but don't demonstrate disorder. Child has 25% chance. Onset usually early in life. Usually effects enzymes

usually recessive. transmitted by heterozygous female, usually only seen in sons. Father doesn't pass to sons, but all daughters will be carriers.

spaces between cells and connective tissue, and between epithelia and supporting vascular and smooth muscle.

around eepithelial cells, edothelial cells, and smooth muscle cells. It is synthesized by epithelium and mesenchymal cells. Type 4 collagen.

mechanical support, the polarity of the cell,

fibrous structural protiens, adhesive glycoproteins, proteoglycans and hyaluronic acid

triple helix of 3 polypeptide alpha chains.
I- everywhere
II- articular cartilage
III- early scar formation
IV- basement membrane

provides the ability to stretch and recoil.

fibronectin, lamininm and integrins

associated with cell surfaces, basement membranes, and pericellular matrices. It binds ECM components and to cells, and regulates the sensetivity of cells to growth factors.

Laminin - (cross) binds to cell receptors on one side, and to matrix components on the other (connects cells to connective tissue). It alters growth, survival, morphology.

integrins

progressive loss of body fat and lean body mass accompanied by profound weakness and anemia. It can appear before the tumor is clinically evident.

TNF - causes decreased appetite
IL-1
IFN-gamma

symptoms that cant be explained by local or distant spread of the tumor, or by the elaboration of hormones indiginous to the tissue from which the tumor arose.Can represent the earliest manifestation of a malignancy, and may mimic metastatic diseases, and occurs in 10-15% of people that are malignant.

Cushing's syndrome, lung disease. Because tumor in lung is producing ACTH w/o any inhibitors

osteolysis caused by a tumor in the bone itself, releasing Ca into the blood.
paraneoplastic - tumor somewhere else producing PTH

thrombi appear in the veins and release thrombogenic factors

increased fluid in the interstitial tissues, abnormal accumulation of fluid within body cavities.

severe general edema

collection of fluid in the abdominal cavity

collection of fluid in the pleural cavity

fluid in the pericardial sac

increased hydrostatic pressure
reduced plasma oncotic pressure
sodium retention
lymphatic obstruction
inflammation

venous obstruction, caused by a thrombosis, external compression, or inactivity of the lower extremity

congestive heart failure, constrictive pericarditis, and cirrhosis

albumin loss because of renal disease-nephrotic syndrome or protein losing gastroenteropathy, and a decreased synthesis of albumin due to liver disease

neoplastic or inflammatory obstruction, surgery, radiation, or parasitic infection

excessive salt and renal insufficiency, decreased renal perfusion

edema effected by gravity and body position

blushing caused by increased blood flow and arteriole dilation (active)

impaired outflow of venous blood (passive)

hemorrhagic shock, loss of more than 20% of blood volume

systemic hypoperfusionowing to a reduction in either cardiac output or in the effective circulating blood volume.

cardiac failure. - can happen because of myocardial damage, ventricular arrhythmias, extrinsic compression, outflow obstruction

systemic microbial infection (mostly gram negative, but can be positive or fungal too)

hypotension, tachycardia, cool clammy skin, oliguria, change in mental status

brain- encephalpathy
kidneys- acute tubular necrosis
heart- contraction band necrosis
lungs- respiratory distress syndrome

decreased vascular flow, embolize, obstruct blood flow

endothelial injury, changes in laminar blood flow, hypercoagulability

A detached intravascular mass that is carried to a distant site from its point of origin

superficial or deep veins of the leg. deep are more likely to embolize at or above the knee

deep veins of the leg (95%)

occludes the main pulmonary artery, and branches into the left and right pulmonary arteries

60%

arterial emboli - come from the heart, from aortic aneurysms, plaques or vegetations on the valves

1st - lower extremity
2nd - brain

microscopic fat globules that enter the blood stream after an injury or fracture to the long bones.

shortness of breathe, difficulty breathing, or painful breathing

fast breath rate

starts 1-3 days after injury, dyspnea, tachypnea, tachycardia, irritable, coma, thrombocytopenia

obstectric procedures, chest wall injury, Iatrogenic, decompresion sickness

100cc

air inhaled at high pressure is dissolved in tissues, when depressured, it bubbles out of solution into the blood

acute decompression sickness, painful gas bubbles form in skeletal muscles and around joints. The bubbles can cause ischemia in other tissues

Caisson Disease - persistence of gas emboli in the skeletal system

amniotic fluid enters the vascular system of mother. develops sudden dyspnea, cyanosis, and hypotensive shock

localized area od ischemic necrosiscaused by obstruction of arterial supply or venous drainage, most commonly caused by arterial thrombosis or emboli

hemorrhagic - occurs in venous occlusions, in loose tissues (spleen), dual circulated organs, previously congested tissues, when flow is reestasblished to a site of previous occlusion and necrosis

anemic, arterial occlusions in solid organs

wedge shaped, has a rim of hyperemia, inflammation, and is usually replaced by a scar

dual blood supply (anastamosis), rate of development (longer gives more time to create other vessels),

persistent regenerative cell replication, hyperplastic and dysplastic proliferation, chronic atrophic gastritus, leukoplakia of oral cavity, vulva, or penis, solar keratosis

products of mutated oncogenes and tumor suppressor genes, overexpressed proteins, tumor antigens from viral infection, oncofetal antigens,

cytotoxic T lymphocytes

natural killer cells, activated by IL-2, can also be activated dependent

secretion of reactive metabolites

activation of the complement system and induction of ADCC by natural killer cells

selective outgrowth of antigen-negative variants, reduced expression of HLA antigens, lack of costimulation, immunosuppression, apoptosis of cytotoxic T-cell

people in nondiseased population

number of cases of a disease in a certain population at a certain time.

number of NEW cases of a disease in a population during a specified time period

probability that a lab test is positive in the presence of disease

probability that a lab test will be negative in the absence of disease

true - # of diseased patients correctly classified by test
false- # of patients w/o a disease miscalssified by test

true- # of patients w/o disease correctly classified by test
false- # of patients w/ disease misclassified by test

probability that a lab result accurately reflects the presence or absnece of a disease

reproductability

the mean is lower than the mode

the mean is higher than the mode

2 humps in the graph

threshold values for lab test results, when value is beyond decision level, the clinician should respond in some way.

disease explained in a cause and effect manner

if patient is less than 60 years old, try to attribute all abnormal lab values to a single cause

test positive/ (true positive + false negatives)

true negative/ (true negative +false positives)

1- activates lipoxygenase pathway for arachadonic aicd metabolism.
2- causes mast cells to degranulate histamine
3- is a chemotactic factor for WBC's