(pathology)

(pathology)

1. 1. etiology

   • study of cause of disease
   • is there a cause?
     • yes
       • usually there are a combination of factors contributing to a cause
       • 3 categories of etiology
         • ginas cooking? appauling
         • genetic
           • genes pass on defect ex: cystic fibrosis
           • genes cause a defect. what kinds of defects are there?
             • structural and functional
               • plasma membrane
                 • separation
               • nucleus
                 • management
               • ER
                 • production
                 • rough (RER)
                   • synthesize fatty acids and phospholipids enzymes detoxify hormones, drugs, toxins
                   • ribosomes
                     • sites where amino acids polymerized to form proteins
                 • smooth
                   • synthesizes plasma membrane, organelle, and secreted proteins
                   • NO ribosomes, but is contineous with RER
               • golgi complexes
                 • packaging, processing, distribution
                 • vesicles that LEAVE golgi can become either
                   • lysosomes
                     • degrades waste
                   • fused to cell membrane
                     • secreted molecules, membrane components
               • lysosomes
                 • maintenance
               • mitochondria
                 • ENERGY
               • cytoskeleton
                 • structural network of filamentous proteins (3) within the cytoplasm
                 • 3 classes of protein fibers
                   • microfilaments (actin) intermediate fibers microtubules
               • separation... management,,, production..... packaging/processing/distribution..... maintenance.... energy.... structural
               • CHECK LISTS THAT DONT FIT!!
         • congenital
         • acquired
     • no
       • idiopathic

2. 2. pathogenesis

   • sequence of events that form the cell or tissues response to the etiological agent sequence goes from initial stimulus to ultimate expression of disease

3. 4 aspects of the disease process

   • 3. morphological changes
     • STRUCTURAL alterations induced in cells/organs.
     • either or:
       • ???? need better explanation
       • characteristic of disease
       • diagnostic of etiological process
   • 4. clinical significance
     • FUNCTIONAL consequences of morphological changes
     • the morphological change influences the normal function and, therefore, produces signs and symptoms

4. pathophysiology

   • pathology WITH emphasis on medical procedures and patient care

5. cell injury

   • 7 BROAD CATEGORIES OF CELL INJURY
     • c
       • chemical agents
       • may damage cells by altering membrane permeability or enzyme integrity but almost any chemical can cause cell injury
         • pollutants. poison. insecticides.
     • o
       • oxygen deprivation
       • hypoxia interferes with aerobic oxidative respiration
         • hypoxia =oxygen deficiency
         • possible causes
           • ischemia ~most common~
             • loss of blood supply in tissue due to impeded (hindered) arterial flow    
           • inadequate oxygenation of blood
             • pneumonia
           • reduction in oxygen carrying capacity of blood
             • anemia and CO poisoning
     • r
       • immunologic (r)eactions
       • whether intended or incidental, can cause cell injury
         • incidental =auto immune disorers like lupus intended= epi pen use (needed)
     • n
       • nutritional imbalances
       • insufficiency of
         • protein-calorie
       • specific _____ ______
         • vitamin deficiencies
       • excess of
         • nutrients
     • p
       • physical agents
       • examples
         • trauma radiation electric shock temperature extremes & sudden changes in atmospheric pressure
     • i
       • infectious agents
       • examples
         • submicroscopic virus bacteria fungi protozoans tape worms
     • g
       • genetic defects genetic abnormalities can have very distinct cell damage
   • biochemical mechanisms of cell injury
     • ATP DEPLETION
     • oxygen deprivation or generation of reactive oxygen species
       • oxygen deprivation
         • lack of oxygen underlies cell injury in ischemia
       • generation of reactive oxygen species
         • partially reduced oxygen species... (free radicals)... cause what?
           • massive damage to LIPIDS in cell membraneS
           • lipids in cell membranes
   • response to cell injury
     • adaptive responses
       • cells reversably adapt to allow for normal function
       • adaptive ->reversible
       • alternative metabolism
         • if oxygen is limited..
           • some cells can use glycolysis to make ATP instead of  oxidative phosphorylation
       • alteration of size
         • hypertrophy
           • cell/organ enlargement in response to increased demand... ex: myocardial cells increase in size in response to pumping through narrowed heart valve
         • hyperplasia
           • increase in # of cells in tissue/organ in response to demands
           • due to hormonal or growth factor stimulation
           • hyper TROPHY is whole organ or cell enlargement because like a trohpy, you get the whole thing. plasia is #
         • atrophy....(remember A-trophy -> A-utophagosomes)
           • shrinking of cell. the reduction in size lowers energy/metabolic requirements. ex: ur muscle if u were bed ridden for a year
           • most commonly because
             • disuse atrophy which is just reduced workload
             • cells shut down specialized functions by...
               • reducing organelle number via lysosomal enzymes (autophagosomes)
         • metaplasia
           • replacing the normal cell type with another cell type that can better withstand the environment
           • happens with epithelial cells
     • production of stress proteins
       • found in cells exposed to low oxygen; originally found in cells stressed by heat
     • organelle changes
       • livers can produce more smooth ER to have more enzymes to degrade toxic chemicals  some cells can produce more mitochondia to address increased ATP demands
     • cell/tissue accumulations
       • happens because injury disrupts either: cell metabolism protein synthesis... substances accumulate in cell
       • hydropic change
         • keyword "hydro"
           • cells fill up with water in response to decrease of atp (the energy currency)
       • fatty change: steatosis;
         • steve oh he is fatty. 
         • diabetes, obesity, anoxia, toxins CCl4
         • fat accumulates as small droplets, turn into huge masses, then....
           • cell swells entire organ can enlarge cells can rupture  fat forms deposits in organs
           • organs that use fat as energy or help synthesize lipids are susceptible
             • kidney heart liver (usually alcohol) DUE TO LOW OXYGEN OR INTOXICATIONS
       • residual bodies
         • undigested materials left behind after phagocytosis because not enough of ...?
           • not enoguh lipofuscin granules or a resistance to them
           • lipofuscin granules are lipid containing residues of lysosomal digestion
         • when u get a tatoo, pigment is encapsulated into residual bodies
       • hyaline change
         • accumulatiion of the pink staining protein
   • most common injury to cell is hypoxia (not enough o2)
   • irreversible cell injury- when the stressor exceeds the cells ability to reversibly adapt
     • damage to cell membranes (plasma and organelle)
     • mitochondrial damage
     • irreversible? membranes and mitochondria
     • what happens after irreversible cell damage? options
       • function at a less than normal level
       • die
         • 2 principle patterns of cell death (thought to be some overlap)
           • necrosis
             • always pathologic. neyo is a pathological liar cells suffer injury. lysosomal enzymes releades into cytoplasm to degrade cell.
             • coagulation necrosis
               • tissues coagulate (become firm)
               • may produce gangreneous necrosis
                 • foul smelling gases from bacteria 
                 • putrefaction
                   • bacteria gain access to area of damage and proliferate =PROCESS OF DECAYING 
               • may produce characteristic cheese like appearance; caseous necrosis
                 • necrosis... tuberculosis 
             • also.. lysosomal cells from immigrant leukocytes help
           • apoptosis
             • not always pathologic = PROGRAMMED CELL DEATH
             • internally regulated series of alterations of cytoplasm/nucleoplasm
               • form masses that become membraneous fragments that are engulfed by ADJACENT cells
   • differential vulnerability to injury? check #1 notes
   • INFLAMMATION
     • a complex reaction in VASCULARIZED C.T. induced by cell injury
     • HEALING
     • designed to eliminate 1. initial cause of injury 2.necrotic cells
     • MAKES WOUND HEALING POSSIBLE
     • 2 basic patterns
       • acute inflammation
         • few minutes to days
         • immeadiate and early response to cell injury
         • A CUTE delivery man named luke broke my mic. i broke down, i needed a tissue
           • designed to deliver leukocytes to site of injury to clear invading microbes and break down necrotic tissue 
         • 5 local signs of acute inflammation: what A CUTE pair of SLIPpeRs
           • S = swelling
           • L= loss of function
           • I= increased heat
           • P= pain
           • R= redness= ERYTHEMA
         • 2 major components (VC= very crucial)
           • V= vascular changes
             • Acute Vascular? AV. Arteriolar vasodilation
               • results in increased blood flow
                 • increased blood ENGORGES down-stream capillary beds
                   • this causes redness and heat
             • micro-vasculature becomes more permeable
               • results in:
                 • exudate
                 • edema
                   • water moves into EXTRA vascular tissue
                 • stasis
                   • increasing blood viscosity/ slows circulation
                   • stasis- slows circulation
           • C= cellular event
             • leukocytes move from microcirculation to injury site
               • includes chemotaxis
             • chemotactic factors induce degranulation
               • degranulation= release of lysosomal enzymes
             • interaction with pathogen induces phagocytosis and degranulation
             • leukocytes can further damage injured tissue. ex: rheumatoid arthritis
           • CONTROL OF V AND C (control of acute inflammatory response
             • both are induced by INITIATORS
               • initiators initiate the inflammatory response IN-directly through chemical mediators
               • chemical mediators
                 • cell-derived
                   • held in cell. cell is activated and histamine is produced by mast cells/platelets
                   • result of encountering cold, heat, trauma, or pathogen......... also from interaction with allergens because antihistamines block histamine action
                   • cause BRIEF increase in venule permeabilit
                 • PLAsma-derived "PLAy in waterfall"- "play in cascades"
                   • plasma derived mediators are produced as a result of 4 cascades that are activated by the circulating protein known as HAGEMAN FACTOR
                   • cascades lead to clotting, pain, complement (membrane attack complex)
                   • proteins in cascade can mediate: vascular dilation, permeability, chemotaxis, phagocytosis, histamine release
         • excessive inflammation can be modified by TED talks, which are like THERAPY
           • a cute teddy bear
           • T emperature
             • reduces swellinh (vasoconstriction and reduced exudate formation just like E +P)
             • do not go beyond 10 mins or
               • cold induces MAST cell degranulation
               • hot induces PHAGOCYTOSIS "hot phag"
             • alternate b/w hot and cold
           • E levation (+pressure)
             • elevating damaged limbs REDUCES BLOOD FLOW and promote DRAINAGE which reduces SWELLING,  pressure with constrictive wrappings can do the same 
           • D rug therapy
             • antihistamines, aspirin, acetomenaphne
       • chronic inflammation
         • days to years
         • when ACUTE response is unable to remove or neutralize the agent the response continues and becomes CHRONIC
         • lasting 6 weeks or more
         • substances involved:
           • microorganisms
             • myobacterium tuberculosis
           • foreign bodies
             • asbestos, silica
         • characterized by ANGIOGENESIS; new blood vessels, tissue destruction, accumalation of macrophages and lymphocytes

6. basic clinical evaulation

   • B_SIC
     • B= begin with history and their personal account of symptoms
       • things clinician cannot detect like pain
     • S= signs; patient gets examined
     • I= Investigation; lab tests or exploratory surgery and findings/results clarify full clinical picture
     • C=conclusion; diagnosis or therapy or prognosis; identification of diease; prognosis is a prediction of disease outcome
       • 4 common approaches for identifying specific type of cell that is injured so can give a proper DIAGNOSIS and appropriate THERAPY
         • FRED wants to know what type of cell he's injured
           • functional release electrical direct (biopsy)
           • F
             • assessment of (F)unctional loss;  observation (bone injury limiting mobility) or a lab test (elevated bilirubin in blood is a liver problem
           • R
             • detection of (R)elease of cell constituents from injured cells;  high k+ in blood means widespread tissue damage bc they were (wrongly) released into blood
           • E
             • monitoring (E)lectrical activity to detect changes from normal
             • electrocardiogram
               • heart problems
             • electroencephalogram
               • activity of brain (encephalus) like if someone has a seizure or is in a coma
             • electromyogram
               • muscle contractions evaluate muscle weakness or paralysis
           • D
             • direct biopsy