Transcript General Principles of Pathophysiology

General Principles of
Pathophysiology
The Normal Cell
Homeostasis
Cellular & Tissue Response to Injury
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
Levels
Cellular Functions
• Organization
• Metabolism
– Catabolism
– Anabolism
• Responsiveness
– Conductivity
• Movement
•
•
•
•
•
•
Reproduction
Growth
Differentiation
Respiration
Secretion
Excretion
Cell Kingdoms
• Prokaryotes
– bacteria
• Eukaryotes
– plants, animals, fungi
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
• 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
•
•
•
•
•
Phospholipid bilayer
Membrane proteins
Cytoplasm
Nucleus
Ribosomes
• Mitochondria
• Endoplasmic
Riticulum
• Golgi Apparatus
• Lysosomes
Generic Eukaryotic Cell
Generic Eukaryotic Cell
Cell Membrane
Fluid Mosaic Model
Phospholipid bilayer w/ proteins
System Integration
• Homeostasis
• Homeo = alike, same
• Stasis = always, staying
Energy Needs of Homeostasis
•
•
•
•
Endothermic vs Exothermic Reactions
Spontaneous vs Nonspontaneous Reactions
‘Coupling’
Metabolism
– Catabolism
– Anabolism
Feedback Loops
• Negative
– Opposes a change
• Positive
– Enhances a change
Feedback Loop Example
Snickers
Snickers
 Blood Glucose
 glucose transport
 glycogen storage
Pancreas  Insulin
Secretion
 Blood Glucose
 Hunger
Methods of Communication
• Endocrine
– Hormones
• Nervous
– Neurotransmitters
Nervous
Endocrine
Wired
Wireless
Neurotransmitters
Hormones
Short Distance
Long Distance
Closeness
Receptor Specificity
Rapid Onset
Delayed Onset
Short Duration
Prolonged Duration
Rapid Response
Regulation
Mechanism of Action
Synaptic Transmission
Synapse
Postsynaptic
Membrane
Pre-synaptic
Membrane
Neurotransmitter
Nervous System
Central N.S.
Autonomic N.S.
Brain
Sympathetic
Spinal Cord
Parasympathetic
Autonomic Nervous System
Sympathetic
Parasympathetic
‘Fight or Flight’
‘’Feed or Breed’
Activation
Restoration
Thoracolumbar
Craniosacral
Adrenergic
Cholinergic
Norepinephrine
Acetylcholine
Sympathetic Receptors
alpha
beta
1
Constriction
( Peripheral
Vascular
Resistance)
 Contractility
 Automaticity
(heart rate)
2
Inhibit further
NE Discharge
Bronchodilation
Vasodilation
General Response to Injury
•
•
•
•
Cellular Adaptation
Mechanisms of Cell Injury
Manifestations of Cell Injury
Cellular Death
Cellular Adaptation
•
•
•
•
•
Atrophy
Hypertrophy
Hyperplasia
Dysplasia
Metaplasia
Atrophy
 Workload
(or disease state)
 Functionality
Efficiency
in disease
-OR- state
Size
Size
organelles
of oforganelles
 Energy Usage
Hypertrophy
 Workload
(or disease state)
 ability to
 Functionality
meet demands!
in disease state
-OR-
Size
Size
organelles
 #of# oforganelles
 contractility
Hyperplasia
 Workload
Physiological state
types:to
2ability
Compensatory
&
meet demands!
Hormonal
...
 tissue
 rate ofsize
by cell
 division
# of cells
 functionality
Hyperplastic endometrium
Dysplasia
Epithelial
Tissue
Pathological
Mutation
Normal Cells
Abnormal
Shape & Size
Cerical Dysplasia
Normal
Tissue
Abnormal
Tissue
Metaplasia
Ex: Cigarette
Smoking
Pathological
Normal Cells
Abnormal
Cells
Replacement
Mechanisms of Injury
• Hypoxic
• Chemical
• Structural
– (trauma…tons next semester!)
• Infectious
• Immunologic / Inflammatory
Hypoxic Injury
 Atmospheric Oxygen
 Respiratory Function
Loss of Hb
 Cardiovascular Function
 Hb function (CO)
 erythropoiesis
Most Common Cause of
Cellular Injury!
Hypoxic Injury (pathway 1)
Elevated
“Markers”
ex CK, CKMB
Loss of
Phospholipids
Membrane
Damage
Release of
Enzymes
Hypoxic Injury (pathway 2)
 mitochondrial
oxygenation
Vacuolization
of mitochondria
 Na+ Pump
Function...
 ATP
Synthesis
 mitochondrial
function
 Glycolysis
(anaerobic
metabolism)...
Hypoxic Injury (pathway 2)
 protein
synthesis
 Na+ Pump
Function...
E.R.
Dilation
 intracellular Na+
 extracellular K+
 intracellular Ca++
 intracellular
H2O
 cellular
function!
Cellular Swelling
& rupture
HypoxicInjury
Injury(pathway
(pathway2)2)
Hypoxic
 Glycolysis
(anaerobic
metabolism)...
Release of
Lysosomal (Digestive)
Enzymes
 Lysosome
Swelling
 Glycogen
Stores
Cellular Digestion
(autodigestion)
 Lactic Acid
+
Na
+
K ATP
pump
Na+
ADP
ATP
K+
Chemical Injury
oxyhemeglobin
Carboxyhemeglobin
Pressure
Manifestations of Injury
• Cellular Swelling
Cool
Graphics
To come!
Physiological Cell Death
Apoptosis
‘Programmed Suicide’
Normal to process of cell
Replacement & Development!
Balance
Ex:Ex:
endometrial
induced
between
apoptosis
the
sloughing
“DOduring
IT!”
during
and
“DON’T
Immune
menstruation
DO response
IT!” voices…
Necrotic Cell Death
Necrotic Cell Death
(pathological)
Coagulative
Gelatinous,
Firm
transparent
& opaque
protein
Liquefactive
Walled-Off
Brain & neurons
Liquid Goo
Caseous
Mycobacterium
‘Cased’-Off
Cheese
tuberculosis
Globules
Fatty
Opaque, Chalky
Breast, pancreas
Soapy
Coagulative Necrosis - Kidney
Necrosis
Liquefactive Necrosis - brain
Necrosis
Caseous
Necrosis
Typical of TB
tubercule
Necrosis
Fatty Necrosis - pancreas
Necrosis
Cirrhosis of the liver
Necrosis
Note nodular
surface
Gangrene
Caused by severe hypoxic injury
Dry
Coagulative
Wet
Liquefactive
Gas
Release
Tissues
Clostridium
gas
not into
just cells!
tissue
Dry Gangrene
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/