370: Pathophysiology Flashcards
1st Line of Defense
Physical, Mechanical and Biochemical Barriers
2ns Line of Defense
The inflammatory response
3rd line of Defense
Adaptive immunity
- Cell-mediated immunity
- Humoral immunity
Physical and mechanical barriers such as skin, low temperature, mucus membranes, mechanical cleansing, and cilia.
1st line of Defense
What are the 2 biochemical barriers?
- Epithelial-Derived Chemicals (cathelicidins, defensins, and collectins)
- Bacteria-Derived Chemicals
(Normal bacterial flora)
What are 3 main Epithelial-Derived Chemicals or antimicrobial peptides?
- Cathelicidins
- Defensins
- Collectins
What is the normal bacterial flora in the vagina?
Lactobacillus
What is the normal bacterial flora of the skin?
Pseudomonas aeruginosa
Why does a 3rd Degree burn increase risk for bacterial invasion?
1st line of Defense is removed (skin and anti-microbial)
Jump into the 2nd/inflammatory response
The inflammatory response
2nd Line of Defense
What are the properties of 2nd Line of Defense?
- inflammatory response
- non-specific
- intensity depends on severity of injury
What are the two responses of the 2nd Line of Defense ?
- Vascular Response
2. Cellular Response
What causes the inflammatory response?
- Infection
- mechanical damage
- ischemia
- nutrient deprivation
- temperature extremes
- Radiation
Etc
What are the goals of the inflammatory response?
- Neutralizes/diluted the inflammatory agent
- Remove necrotic material
- Establish environment for healing
What causes Redness in the 2nd Line of Defense?
Hyperaemia from vasodilation
What causes Heat in the 2nd Line of Defense?
Increased metabolism at inflammatory site
What causes Pain & tenderness in the 2nd Line of Defense?
- Change in pH
- Nerve stimulation by chemical mediators
- Increased fluid
What causes Edema in the 2nd Line of Defense?
- Fluid shift
2. Accumulation of fluid exudate
What causes loss of function in the 2nd Line of Defense?
Swelling and pain
Why does ph decrease due to cell damage?
Released potassium
Chemotaxis
Movement of leukocytes in response to chemical signal from area of injury
Margination
Free flowing leukocytes initiate close mechanical contact
Diapedesis
Movement of leukocytes to area of damage
Neutrophils
- First to arrive
- Phagocytosis
- Within 6 hours, only live for 24-48 hrs
BANDS released by bone marrow
- When demand of neutrophils is high
Also known as Left shift
Leukocytes involves in the 2nd Line of Defense
Neutrophils
Eosinophils
Basophils
Monocytes
(Nice Monkeys Eat Bananas)
Chemical mediator
Any messenger that acts on BVs, inflammatory cells or other cells to contribute to any inflammatory response.
Also involved in 2nd Line of Defense
Histamine
Stored in granules of basophils, last cells, platelets
Mechanism of action of histamine
Causes vasodilation and increased vascular permeability
Kinins
Arise from polypeptides that circulate in the blood in inactive form, Kininogens
Mechanism of action of Kinins
Cause contraction of smooth muscle and dilation of BVs —> pain
Complement components (C3a, C4a, C5a)
Anaphylatoxic agents generated from complement pathway activation
Mechanism of action of Complement components (C3a, C4a, C5a)
- Stimulate histamine release
2. Stimulate chemotaxis
Prostaglandins and Leukotrienes
Produced from arachidonic acid.
Contribute to vasodilation, capillary permeability, pain and fever, leukotriene B4 stimulates chemotaxis
Cytokines
Secreted by various cells
Effects vary
The characteristic vascular change at the site of an injury produce:
Increased permeability and leakage
3rd Line of defense
- Adaptive immunity
- Specific response, occurs more slowly than inflammatory response
- Can be induced by vaccination
A molecule that can react with antibodies or receptors on B and T cells
Antigen
An antigen that can trigger an immune response
Immunogenic antigen
The ability of a particular substance to provoke an immune response
Immunogenicity
Protein made specifically against an antigen
Antibody
What are the 2 forms of of adaptive immune system or 3rd line of defense?
- Humoral (antibody-mediated) immunity
2. Cell-mediated immunity
What are the 3 Antibody functions?
Direct: 1. Neutralization 2. Agglutination Indirect 3. Opsonization
Antibody neutralization
Block binding or inactive antigen to receptor on receptor cell
Agglutination
Link microns together
Clumped antigen then filtered out by blood, lymph, or phagocytosis more easily
Opsonization
Marking for ingestion by phagocytes.
Antibodies bind to cell membrane of pathogen.
Antibody titres
Blood test for amoun of antibodies.
Determines if patient is vaccinated and correlated to strength of immune response.
IgG
- Most prevalent
- Most of protective activity against infection
- Crosses the placenta
IgA
- Mostly in secretions
2. Most of protective activity in bonds secretions
IgE
- Most rare
- Mediator of many common allergic responses
- Defends against parasitic infections
IgD
- Not well known
2. Functions as one type of B-cell antigen receptor
IgM
- Largest
2. First antibody produced during the initial, or primary, response to an antigen
Which antibody is most prevalent in the body?
IgG
Which antibody is most rare in the body?
IgE
Which antibody is most protective against infection and crosses the blood brain barrier?
IgG
Which antibody is mediator for allergic responses and defends parasitic infections?
IgE
Latent phase of primary immune response
B-cell differentiation
Which antibody is found in saliva and other body secretions?
IgA
Which neurotransmitter is most prevalent in the brain?
Glutamate
Negative symptoms of schizophrenia
Decreased motivation
Blunted affect
Poor self-care
Social withdrawal
Positive symptoms of schizophrenia
Hallucinations
Delusions
Paranoia
Agitation
Cognitive symptoms of schizophrenia
Disordered thinking
Memory and learning
Lack of focus
Pathophysiology of schizophrenia
- Dysregulation of dopamine (up or down)
2. Imbalance of dopamine and serotonin
First generation antipsychotics (FGA)
- D2 antagonists (decrease dopamine transmission)
- Blockade on receptors for:
Acetylcholine Histamine Norepinephrine Serotonin Dopamine
- Classified by potency
Second generation antipsychotics (SGAs) aka Atypical agents
- Decreased serotonin transmission
- Low affinity for D2 receptors
(Serotonin has inhibitory effects on DA)
Medicated cooperative stage
1st week of antipsychotic action
Decreased agitation, hostility
Improved socialization stage
2-6 week of antipsychotic action
Obeys rules, attends meetings, etc
Elimination of thought disorder stage
2 weeks - months of antipsychotic action
Decreased delusions, hallucinations, thought disturbances
Maintenance Stage of antipsychotic action
Achieves baseline level of functioning
Positive symptoms of schizophrenia
Too much dopamine in MESOLIMBIC area
Treat with FGAs (D2 blockers) or SGAs
Negative symptoms of schizophrenia
Not enough dopamine in MESOCORTICAL area
Treat with SGAs (restore balance between serotonin and dopamine)
Protype of First Gen Antipsychotic
Chlorpromazine
Low potency agents of FGA
(Low D2 affinity, non selective)
Sedation, orthostatic hypotension, anticholinergic effects, weight gain
High potency agents of FGAs
(High D2 affinity/selectivity)
Extrapyramidal symptoms, prolactin release, arrhythmias
Prototype of high potency agent of FGA
Haloperidol
Extrapyramidal Symptoms
- Movement disorders
- Due to blockade of D2 receptors in nigrostriatal region
- Low DA, high Ach
Extrapyramidal movement disorders
High potency agents, occur early:
- Acute dystopia
- Parkinsonism
- Akathisia
Prolonged med use:
4. Tardive Dyskinesia
Severe spasm of muscles in tongue, face, neck, back
Acute dystopia
Treated with anticholinergics
Tremor, rigidity, slow shuffling gait
Parkinsonism
Treated with anticholinergics
Profound restlessness, pacing, movement
Akathisia
Treated with anticholinergics
Involuntary twisting, writhing movements of face, tongue; may be irreversible, no reliable treatment
Tardive Dyskinesia
Treated with anticholinergics
Anticholinergics
(Benztropine, diphenhydramine)
Restore balance between DA and Ach
Neuroleptic Malignant Syndrome (NMS)
- More likely with high potency antipsychotics
Sudden fever, muscle rigidity, sweating, increased HR, labile BP, altered LOC, confusion, seizures, coma, arrhythmia, death
D/c antipsychotics, no antidote
Prototype of Second Gen Antipsychotics
Olanzapine
Others: Risperidobe, Clozapine
Blockade of 5-HT2 receptors (restore DA/5HT balance)
Side effects: weight gain
Side effects of Second Gen Antipsychotics
Weight gain, diabetes, increased cholesterol, prolonged QT interval
Clozapine
Risk of agranulocytosis
Agranulocytosis
Drop in blood cell counts
Could be fatal due to sepsis
Monitor WBC and neutrophil counts
Monoamine hypothesis of depression
Deficit of one or more NE, 5HT, or DA neurotransmission
Principal symptoms of depression
Depressed mood, loss of interest/pleasure
Respond by 4 weeks