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IntroPatho

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IntroPatho Powered By Docstoc
					   General Principles of
   General Principles of
    Pathophysiology
     Pathophysiology


          The Normal Cell
          The Normal Cell
            Homeostasis
            Homeostasis
Cellular & Tissue Response to Injury
Cellular & Tissue Response to Injury
                  Topics
                  Topics
• Discuss the structure and function of normal
  cells
• Describe the mechanisms for the general
  maintenance of homesostasis
• Discuss the general responses to injury
Structural
Structural
 Levels
  Levels
           Cellular Functions
           Cellular Functions
• Organization      •   Reproduction
• Metabolism        •   Growth
  – Catabolism      •   Differentiation
  – Anabolism       •   Respiration
• Responsiveness    •   Secretion
  – Conductivity
                    •   Excretion
• Movement
               Cell Kingdoms
               Cell Kingdoms
• Prokaryotes
  – bacteria
• Eukaryotes
  – plants, animals, fungi
      Building Blocks of Life
      Building Blocks of Life
• Amino Acids -> Proteins
  – Structure & Function
• Nucleic Acids -> DNA / RNA
  – Information Transmission, energy storage
• Simple Sugars -> Polysaccharides
  – Energy Sources, structure
• Fatty Acids -> Lipids
  – Structure, Energy Source
       Human Genome as a Book
       Human Genome as a Book
• There are 23 chapters, called CHROMOSOMES
• Each chapter contains several thousand stories,
  called GENES
• Each story is made up of paragraphs, called
  EXONS
• Each story is interrupted by advertisements called
  INTRONS
• Each paragraph is made up of words, called
  CODONS.
• Each word is written in letters called BASES
Speaking of DNA…
           Cellular Components
           Cellular Components
•   Phospholipid bilayer   • Mitochondria
•   Membrane proteins      • Endoplasmic
•   Cytoplasm                Riticulum
•   Nucleus                • Golgi Apparatus
•   Ribosomes              • Lysosomes
     Generic Eukaryotic Cell
     Generic Eukaryotic Cell

Generic Eukaryotic Cell
Cell Membrane
Cell Membrane
   Fluid Mosaic Model
   Fluid Mosaic Model

Phospholipid bilayer w/ proteins
          System Integration
          System Integration
• Homeostasis
• Homeo = alike, same
• Stasis = always, staying
    Energy Needs of Homeostasis
    Energy Needs of Homeostasis
•   Endothermic vs Exothermic Reactions
•   Spontaneous vs Nonspontaneous Reactions
•   ‘Coupling’
•   Metabolism
    – Catabolism
    – Anabolism
             Feedback Loops
             Feedback Loops
• Negative
  – Opposes a change
• Positive
  – Enhances a change
    Feedback Loop Example
    Feedback Loop Example
          Snickers     ⇑ Blood Glucose
                       ⇑ Blood Glucose
        Snickers




⇑ glucose transport
⇑ glucose transport   Pancreas ⇑ Insulin
⇑ glycogen storage
 ⇑ glycogen storage      Secretion




 ⇓ Blood Glucose           ⇑ Hunger
                           ⇑ Hunger
   Methods of Communication
   Methods of Communication
• Endocrine
  – Hormones
• Nervous
  – Neurotransmitters
    Nervous
    Nervous             Endocrine
                        Endocrine


     Wired
     Wired               Wireless
                         Wireless

Neurotransmitters
Neurotransmitters       Hormones
                        Hormones

 Short Distance
 Short Distance       Long Distance
                      Long Distance

   Closeness
   Closeness        Receptor Specificity
                    Receptor Specificity

  Rapid Onset
  Rapid Onset         Delayed Onset
                      Delayed Onset

 Short Duration
 Short Duration     Prolonged Duration
                    Prolonged Duration
Rapid Response
Rapid Response          Regulation
                        Regulation
Mechanism of Action
Mechanism of Action
            Synaptic Transmission
            Synaptic Transmission
  Synapse
  Synapse                               Post-
                                         Post-
                                        synaptic
                                         synaptic
                                        Membrane
                                         Membrane




Pre-synaptic
Pre-synaptic
Membrane
Membrane
                     Neurotransmitter
                     Neurotransmitter
      Nervous System
      Nervous System

Central N.S.
Central N.S.    Autonomic N.S.
                Autonomic N.S.




  Brain
  Brain          Sympathetic
                 Sympathetic

Spinal Cord
Spinal Cord    Parasympathetic
               Parasympathetic
Autonomic Nervous System
Autonomic Nervous System
 Sympathetic
 Sympathetic          Parasympathetic
                      Parasympathetic

 ‘Fight or Flight’
  ‘Fight or Flight’    ‘’Feed or Breed’
                        ‘’Feed or Breed’

    Activation
    Activation           Restoration
                         Restoration

 Thoracolumbar
 Thoracolumbar          Craniosacral
                        Craniosacral

   Adrenergic
   Adrenergic            Cholinergic
                         Cholinergic

 Norepinephrine
 Norepinephrine         Acetylcholine
                        Acetylcholine
    Sympathetic Receptors
    Sympathetic Receptors
        alpha
        alpha               beta
                            beta
     Constriction
      Constriction      ⇑ Contractility
                        ⇑ Contractility
     (⇑ Peripheral
      (⇑ Peripheral
1
1                       ⇑ Automaticity
                        ⇑ Automaticity
        Vascular
        Vascular          (heart rate)
                           (heart rate)
        Resistance)
        Resistance)


     Inhibit further    Bronchodilation
                        Bronchodilation
2
2     Inhibit further
     NE Discharge       Vasodilation
                        Vasodilation
      NE Discharge
      General Response to Injury
      General Response to Injury
•   Cellular Adaptation
•   Mechanisms of Cell Injury
•   Manifestations of Cell Injury
•   Cellular Death
          Cellular Adaptation
          Cellular Adaptation
•   Atrophy
•   Hypertrophy
•   Hyperplasia
•   Dysplasia
•   Metaplasia
                      Atrophy
                      Atrophy

   ⇓ Workload
   ⇓ Workload                        ⇓⇓Size
                                      ⇓⇓Size
                                         Size
                                          Size
(or disease state)
 (or disease state)                 oforganelles
                                of oforganelles
                                of organelles
                                       organelles




   ⇓ ⇑ Efficiency
      ⇑ Efficiency
   ⇓Functionality
      Functionality
   in disease state
         -OR-
          -OR-
    in disease state             ⇓ Energy Usage
                                 ⇓ Energy Usage
               Hypertrophy
               Hypertrophy

   ⇑ Workload
   ⇑ Workload                  ⇑⇑⇑Size
                               ⇑ Size
                                  Size
                                   Size
(or disease state)
 (or disease state)     ⇑ #⇑⇑ofoforganelles
                        ⇑ # organelles
                             ## organelles
                            ofof organelles



     ⇑ ability to
      ⇑ ability to
   ⇓ Functionality
   ⇓ Functionality
   meet demands!
    meet demands!
   in disease state
    in disease state
         -OR-
          -OR-               ⇑ contractility
                             ⇑ contractility
              Hyperplasia
              Hyperplasia

   ⇑ Workload
   ⇑ Workload
Physiological state
Physiological state
                        ⇑ tissueofsize
                           ⇑ rate of
                            ⇑ rate
                       by ⇑ # of cells
                          cell division
                          cell division



    ⇑2ability to
       types:
     ⇑2ability to
        types:
  Compensatory &
   meet demands!
  Compensatory &
   meet demands!
    Hormonal
         ...
     Hormonal
          ...               ⇑ functionality
                            ⇑ functionality
Hyperplastic endometrium
Hyperplastic endometrium
               Dysplasia
               Dysplasia

Pathological                   Epithelial
Pathological                    Tissue




                    Mutation
  Normal Cells                   Abnormal
                                Shape & Size
         Cerical Dysplasia
         Cerical Dysplasia

Normal              Abnormal
Tissue               Tissue
           Metaplasia
           Metaplasia

Pathological                   Ex: Cigarette
Pathological                     Smoking




  Normal Cells                     Abnormal
                                     Cells
                 Replacement
        Mechanisms of Injury
        Mechanisms of Injury
• Hypoxic
• Chemical
• Structural
  – Tramua
• Infectious
• Immunologic / Inflammatory
              Hypoxic Injury
              Hypoxic Injury

⇓ Atmospheric Oxygen
⇓ Atmospheric Oxygen    ⇓ Respiratory Function
                        ⇓ Respiratory Function
Loss of Hb
Loss of Hb              ⇓ Cardiovascular Function
                        ⇓ Cardiovascular Function
⇓ Hb function (CO)
⇓ Hb function (CO)
⇓ erythropoiesis
⇓ erythropoiesis


             Most Common Cause of
             Most Common Cause of
                Cellular Injury!
                 Cellular Injury!
Hypoxic Injury (pathway 1)
Hypoxic Injury (pathway 1)

                                 Elevated
                                 Elevated
    Loss of
     Loss of                   “Markers”
                                “Markers”
  Phospholipids
  Phospholipids              ex CK, CKMB
                              ex CK, CKMB


                  Membrane
                  Membrane
                   Damage
                   Damage

                              Release of
                              Release of
                              Enzymes
                               Enzymes
    Hypoxic Injury (pathway 2)
    Hypoxic Injury (pathway 2)

              ⇓ mitochondrial     ⇓ Na++Pump
                                  ⇓ Na Pump
              ⇓ mitochondrial
                oxygenation        Function...
                                   Function...
                 oxygenation




 Vacuolization
  Vacuolization      ⇓ ATP
                     ⇓ ATP
of mitochondria
 of mitochondria    Synthesis
                    Synthesis

                                  ⇑ Glycolysis
                                  ⇑ Glycolysis
               ⇓ mitochondrial
               ⇓ mitochondrial     (anaerobic
                                    (anaerobic
                  function
                   function      metabolism)...
                                 metabolism)...
            Hypoxic Injury (pathway 2)
            Hypoxic Injury (pathway 2)
        ⇓ Na++Pump                       ⇓ protein
                                         ⇓ protein
        ⇓ Na Pump
         Function...                     synthesis
                                          synthesis
         Function...
                             E.R.
                              E.R.
                            Dilation
                            Dilation
⇑ intracellular Na++
⇑ intracellular Na                       ⇓ cellular
                                         ⇓ cellular
⇑ extracellular K++
⇑ extracellular K                        function!
                                          function!
⇑ intracellular Ca++
⇑ intracellular Ca++


          ⇑ intracellular
          ⇑ intracellular              Cellular Swelling
                                       Cellular Swelling
               H22O
                HO                        & rupture
                                           & rupture
     Hypoxic Injury (pathway 2)
      Hypoxic Injury (pathway 2)
     Hypoxic Injury (pathway 2)
 ⇑ Glycolysis
 ⇑ Glycolysis                         Release of
                                      Release of
  (anaerobic
   (anaerobic                    Lysosomal (Digestive)
                                 Lysosomal (Digestive)
metabolism)...
metabolism)...                         Enzymes
                                       Enzymes

                 ⇑ Lysosome
                 ⇑ Lysosome
                   Swelling
                   Swelling
⇓ Glycogen
⇓ Glycogen
  Stores
   Stores
                                   Cellular Digestion
                                   Cellular Digestion
                                    (autodigestion)
                                     (autodigestion)
                 ⇑ Lactic Acid
                 ⇑ Lactic Acid
  + K+ ATP pump
Na + K+ ATP pump
Na

                   Na++
                   Na




         ATP
         ADP
         ATP
         ADP
                   K++
                   K
             Chemical Injury
             Chemical Injury

                               oxyhemeglobin
Saturation




                                 Carboxy-
                                 hemeglobin




                   Pressure
      Manifestations of Injury
      Manifestations of Injury
• Cellular Swelling
                             Cool
                           Graphics
                           To come!
Physiological Cell Death
Physiological Cell Death

Apoptosis
Apoptosis                   Programmed Suicide’
                           ‘‘ProgrammedSuicide’



        Normal to process of cell
        Normal to process of cell
      Replacement & Development!
      Replacement & Development!



        Ex: induced apoptosis during
      Ex: endometrial sloughingIT!”and
     Balanceinducedapoptosis duringand
      Ex: endometrial the “DOIT!”
     Balancebetween the “DO during
        Ex: between sloughing during
                menstruation
              Immune response
         “DON’T DO response
          “DON’T DOIT!” voices…
               Immune IT!” voices…
                 menstruation
Necrotic Cell Death
               Death
Necrotic Cell Cell Death
     Necrotic
(pathological)
(pathological)
                           Firm
                        Gelatinous,
                            Firm
                         Gelatinous,
 Coagulative
 Coagulative             & opaque
                    transparent protein
                         & opaque
                     transparent protein
                      Walled-Off
                      Walled-Off
 Liquefactive
 Liquefactive       Brain & neurons
                    Brain & neurons
                      Liquid Goo
                       Liquid Goo
                     ‘‘Cased’-Off
                       Cased’-Off
                    Mycobacterium
                     Mycobacterium
  Caseous
  Caseous             tuberculosis
                    Cheese Globules
                       tuberculosis
                    Cheese Globules
                    Opaque, Chalky
                    Opaque, Chalky
    Fatty
    Fatty           Breast, pancreas
                    Breast, pancreas
                        Soapy
                         Soapy
Coagulative Necrosis -- Kidney
Coagulative Necrosis Kidney

                       Necrosis
Liquefactive Necrosis -- brain
Liquefactive Necrosis brain

                        Necrosis
Caseous
Caseous         Necrosis

Necrosis
Necrosis


Typical of TB
  tubercule
Fatty Necrosis -- pancreas
Fatty Necrosis pancreas
                        Necrosis
Cirrhosis of the liver
Cirrhosis of the liver
                         Necrosis
                Note nodular
                  surface
        Gangrene
        Gangrene
  Caused by severe hypoxic injury
  Caused by severe hypoxic injury



Dry
Dry                           Coagulative
                              Coagulative


Wet
Wet                           Liquefactive
                              Liquefactive


Gas
Gas                           Clostridium
                         Tissues not just tissue
                         Release gas into cells!
                              Clostridium
Dry Gangrene
Dry Gangrene
Wet Gangrene 2º to diabetes
Wet Gangrene 2º to diabetes

                   Necrosis
                w/ liquefactive
                 component
               Web Resources
• Cell Membrane:
   – http://www.d.umn.edu/~sdowning/Membranes/lecturen
     otes.html#anchor360899
• Sodium Potassium ATP pump:
   – http://arbl.cvmbs.colostate.edu/hbooks/molecules/sodiu
     m_pump.html
• Kimbal’s Biology Page(s): You want it, he’s got
  it!:
   – http://www.ultranet.com/~jkimball/BiologyPages/T/TO
     C.html
             Web Resources
• Virtual Library of Cell Biology:
  – http://vl.bwh.harvard.edu/
• On-line pathophysiology course:
  – http://sonser4.nur.uth.tmc.edu/patho/

				
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posted:2/11/2012
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