MOD #15 Dr Putthoff Fri 4/25/03 9AM Scribe: Rosaline Sharifi **Because Dr. Putthofff does not review scribes please email me if you find any corrections that need to be made** REVIEW/DISCUSSION CELLULAR PATHOLOGY I Dr. Putthoff was late to class. Class started at 9:15 AM. Reminders before class started: Monday morning: Dr. Putthoff’s review 9-10AM Dr. Wasson’s review 10-11AM 11-12PM CIL/quiz (for a grade) **His powerpoints are in regular print, comments he added are italicized. He said to especially know his rhetoric questions that are in his powerpoints. He said he is going straight from Robbins, so refer to the book for figures** I. Chapters 1 and 2, Robbin text - Cell Injury and Cell Death ( Chapter 1) o Can see cell injury through microscopes and sometimes grossly o Grossly- will see it as a scar on surface on skin. Scar composed of fibrous tissue and collagen - Adaptations, Intracellular Accumulations, Cell aging (Chapter 2) II. Chapter 1: Cell Injury and Cell Death - Define and review discussion of: 1) Etiology or cause o Example: microorganism that is non-pathogenicimmunocompromise o Toxins: example- overdose of tylenol and aspirin 2) Pathogenesis (define)… o a sequence of events , starts out with an etiologic events, not just one element you can point to o What is the toxin’s mechanism of injury? o Etiologic process 3) Morphologic changes o Early changes (cellular swelling) through involution of cells w/ loss of cellular material (karyoxis) 4) Functional derangements and clinical significance (How are signs and symptoms related to this?) Know difference between ischemia and hypoxia!! Ischemia more injurious to cell than hypoxia. Mitochondria extremely susceptible to hypoxia and ischemia. 5) Other under “definitions” o Ex: hypertrophy, atrophy, metaplasia, hyperplasia o Hypertrophy (increase in size of individual cells) vs. hyperplasia (increase in number of cells) III. Definitions or terms for fundamental understanding - Normal homeostasis - Cellular adaptive responses: physiologic or pathologic - Hypertrophy (vs. hyperplasia?) - Atrophy o Can use it on macroscopic and microscopic level o Hypoplastic- smaller than normal - Cell injury (Table 1-1, pg 4) Important concepts to know o reversible irreversiblecell death LOOK AT FIG1-1 PG 3 - What is it? What does it show? Myocardial infarction What does it mean to a patient? How did this likely present clinically? Table 1-1, pg 4 IV. Two principal patterns of cell death - What are the common reasons or etiologies of cell death? o Ischemia is most common - Necrosis (types?) o Definition: cell death o Know coagulative vs liquefactive vs caseous necrosis - Apoptosis o Definition: Programmed cell death Physiologic example: embryogenesis, menses Pathologic example: cancer population of cells - Overlap?- “oncosis” o overlap of cells as they approach for the potential of irreversible cell death V. Cellular Pathology I -Causes of Cell Injury o Oxygen deprivation ** most important** (hypoxia vs. ischemia) o o o o o o VI. - Examples: Coronary artery disease, stroke, pulmonary fibrosis, peripheral vascular disease Physical agents Mechanical trauma Chemical agents and drugs All drugs have some sort of side effects related to them Ex: Tylenol and aspirin overdose Infectious agents Immunologic agents Example: Autoimmune Disease- Lupus 1. Affects more woman than men 2. Antibody that attacks double stranded DNA Genetic derangements Nutritional imbalances Not as big of a problem in U.S, but is big problem in other areas of world Many children have variety of nutritional problems. 1. Example: don’t get enough protein 2. Lead intoxication- cognitive defects and peripheral neuropathies result from this Cell Injury and Necrosis “ The cellular response to injury depends on the type of injury, its duration, and its severity” “The consequences of injury depend upon the type, state, and adaptability of the injured cell” VII. Four intracellular systems particularly vulnerable to injury - Outer cell membrane o What happens in outer cell membrane? 1. Na/K ATPase pump 2. Ca2+ balance - Aerobic respiration Oxidative phosphorylation occurs in mitochondria - Protein synthesis Proteins or proteins complexed with other substances that are biologically active - Nuclear DNA Complexed with histones so somewhat protected but still vulnerable to injury Example: UV radiation VIII. Cell Injury and Necrosis (continued) - “The structural and biochemical elements of the cell are so closely interrelated that whatever the precise point of initial attack, (significant) injury at one locus (often) leads to wide-ranging secondary effects” Liver- capable of tremendous regeneration, giant biochemical factory - “The morphologic changes of cell injury become apparent only after some criticial biochemical system with the cell has been deranged” IX. General Biochemical Mechanisms- Know what they are! - Injurious agents, toxins - Particularly vulnerable a. Glycolysis b. Citric acid cycle- not as important as the other (a or c) c. Oxidative phosphorylation Glycolysis and oxidative phosphorylation particularly important because this is where most of ATP comes from X. - XI. General Biochemical Mechanisms (Continued) Examples of injurious agents: cyanide, Clostridium perfringens a. What is Clostridium perfringens and what does it cause? gangrene Not all injurious elements are well defined or understood in terms of their primary biochemical attack locus, etc Cellular Pathology I - ATP depletion (what two major mechanisms/sites generate ATP?) Oxidative phosporylation and glycolysis - Oxygen and oxygen- derived free radical As a cause of aging or mutation - Intracellular Ca2+ and loss of Ca2+ homeostasis (subsequent events?) May cause cell death - Defects in membrane permeability - Irreversible mitochondrial damage Will cause a loss of oxidative phosphorylation Sidenote: Dr. Putthoff went through figures out of Robbins. Fig 1-2 Fig 1-3 + Fig 1-4 These may appear on his exams, but he said they are more for System II courses and not necessarily Mechanisms of Disease (Figure 1-3) i. villi on cell, probably a glandular cell, means that it secretes something ii. Figure shows effect of increased Ca2+ on the cell iii. Ca2+ will activate different enzymes to carry out functions XII. - Mitochondria (Fig 1-4) There are 2 major types of injury to the mitochondria 1) 2) Toxins a) Cytochrome c- causes variety of injuries b) Mitochondrial Permeability transition- ingress for various injurious substances to damage both the outer and inner mitochondrial membrane c) Can tell what a cell does by the shape of the mitochondria Ischemia or hypoxia (Ischemia more common)