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 Responsiveness Movement 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

Cell Membrane

Phospholipid bilayer w/ proteins 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  Blood Glucose Snickers Pancreas  Insulin Secretion  glucose transport  glycogen storage  Blood Glucose  Hunger

Methods of Communication Endocrine Hormones Nervous Neurotransmitters

Nervous Endocrine Wireless Wired 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 Post-synaptic 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 Constriction ( Peripheral Vascular Resistance)  Contractility  Automaticity (heart rate) 1 Bronchodilation Vasodilation Inhibit further NE Discharge 2

General Response to Injury Cellular Adaptation Mechanisms of Cell Injury Manifestations of Cell Injury Cellular Death

Cellular Adaptation Atrophy Hypertrophy Hyperplasia Dysplasia Metaplasia

Atrophy  Size of organelles  Workload (or disease state)  Efficiency -OR-  Functionality in disease state  Energy Usage

Hypertrophy  Size  # of organelles  contractility  Workload (or disease state)  Functionality in disease state  ability to meet demands! -OR-  contractility

Hyperplasia  tissue size by  # of cells  rate of cell division  Workload Physiological state  rate of cell division  tissue size by  # of cells 2 types: Compensatory & Hormonal  ability to meet demands! ...  functionality

Hyperplastic endometrium

Dysplasia Epithelial Pathological Tissue Mutation Normal Cells Abnormal Shape & Size Mutation

Cerical Dysplasia Normal Tissue Abnormal Tissue

Metaplasia Ex: Cigarette Pathological Smoking Normal Cells Abnormal Replacement

Mechanisms of Injury Hypoxic Chemical Structural Infectious (trauma…tons next semester!) Infectious Immunologic / Inflammatory

Hypoxic Injury Most Common Cause of Cellular 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  Na+ Pump Function... Vacuolization of mitochondria  ATP Synthesis  Glycolysis (anaerobic metabolism)...  mitochondrial function

Hypoxic Injury (pathway 2)  Na+ Pump Function...  protein synthesis E.R. Dilation  cellular function!  intracellular Na+  extracellular K+  intracellular Ca++  intracellular H2O Cellular Swelling & rupture

Hypoxic Injury (pathway 2)  Glycolysis (anaerobic metabolism)... Release of Lysosomal (Digestive) Enzymes  Glycogen Stores  Lysosome Swelling Cellular Digestion (autodigestion)  Lactic Acid

Na+ K+ ATP pump Na+ ATP ADP ATP K+

Chemical Injury oxyhemeglobin Saturation Carboxy- hemeglobin Pressure

Manifestations of Injury Cellular Swelling Cool Graphics To come!

Physiological Cell Death Apoptosis ‘Programmed Suicide’ Normal to process of cell Replacement & Development! Balance between the “DO IT!” and “DON’T DO IT!” voices… Ex: induced apoptosis during Immune response Ex: endometrial sloughing during menstruation

Necrotic Cell Death (pathological) Necrotic Cell Death Coagulative Gelatinous, transparent protein Firm & opaque Liquefactive Brain & neurons Walled-Off Liquid Goo Caseous Mycobacterium tuberculosis ‘Cased’-Off Cheese Globules Fatty Breast, pancreas Opaque, Chalky Soapy

Coagulative Necrosis - Kidney

Liquefactive Necrosis - brain

Caseous Necrosis Necrosis Typical of TB tubercule

Fatty Necrosis - pancreas

Cirrhosis of the liver Necrosis Note nodular surface

Gangrene Caused by severe hypoxic injury Dry Coagulative Wet Liquefactive Gas Clostridium Release gas into tissue Tissues not just cells!

Dry Gangrene

Wet Gangrene 2º to diabetes Necrosis w/ liquefactive component

Web Resources Cell Membrane: Sodium Potassium ATP pump: http://www.d.umn.edu/~sdowning/Membranes/lecturenotes.html#anchor360899 Sodium Potassium ATP pump: http://arbl.cvmbs.colostate.edu/hbooks/molecules/sodium_pump.html Kimbal’s Biology Page(s): You want it, he’s got it!: http://www.ultranet.com/~jkimball/BiologyPages/T/TOC.html

Web Resources Virtual Library of Cell Biology: http://vl.bwh.harvard.edu/  On-line pathophysiology course: http://sonser4.nur.uth.tmc.edu/patho/