Introduction to Pathophysiology and Cellular Basis of Disease Part 2

○ ■ ■ ■ ■ ○ Metabolic acidosis ● HCO3- is LOW in both “primary disturbance” and “compensation” ○ This is the source of the problem. low HCO3- (base) = too acidic ■ To bring up pH → PCO2 (CO2 in blood) decreases by HYPERVENTILATION (get rid of CO2) Metabolic alkalosis ● HCO3- is HIGH in both ○ High HCO3- (base) = too alkaline ○ To lower pH → PCO2 (CO2 in blood) increases by HYPOventilation (retain CO2) Respiratory acidosis ● PCO2 is HIGH in both ○ High PCO2 (acidic) = too acidic ○ To increase pH → HCO3- (base) must increase Respiratory alkalosis ● PCO2 is LOW in both ○ Low PCO2 (acidic) = too basic ○ To decrease pH → HCO3- (base) must decrease ○ ■ MEMORIZE RANGE Example ■ ○ ○ ○ ● A Step 1: WHAT IS pH: acidosis, alkalosis, normal? 2. Evaluate CO2 ■ High CO2 = acidotic change ■ CO2 levels linked to respiratory ○ 3. Evaluate HCO3■ High HCO3- = basic change ■ HCO3- levels linked to metabolic ○ 4. Match CHANGE IN CO2/HCO3- to pH. ■ One of the two that has change that matches direction of pH → the cause ■ The change that does not match direction of pH = compensation Bc HCO3- = normal range → UNCOMPENSATED ○ Partially compensated - there’s been some compensation, but pH is still WITHIN ABNORMAL RANGE ■ Ex. if above was “HCO3- = 20” → acidotic change → partially compensated ○ Fully compensated - pH is back in NORMAL RANGE ■ ● ● D Cell metabolism ○ 3 basic steps of cell metabolism ■ Glycolysis (occurs in cytosol) ● ● Produces 2 ATP ■ Citric acid cycle/Krebs (mitochondria) ● Produces 2 ATP ■ Oxidative phosphorylation (mitochrondria) ● Produces 32 ATP → only step that requires O2 (final eacceptor) ● Shows importance of O2 in body ○ Control of cell transport ■ Passive transport ● Simple diffusion ● Osmosis ● Facilitated diffusion ■ Active transport ● Secondary active transport ● Primary active transport Cellular stress and injury ○ How body responds determines pathogenesis → leads to signs and symptoms ○ LOW LEVEL STRESSORS ■ Don’t cause immediate injury/cell death ■ Will change cell functions that bring up clinical manifestations ○ MILD and PERSISTENT stress ■ Adaptation of cells. Change function and clinical manifestations ● Ex. increase/decrease functional demand ● If stress isn’t reversed early, can become injuries to pt Mechanisms of cell injury ○ Hypoxic injury ■ ● ■ ■ ● ● Ischemia - reduction in blood flow that can cause hypoxia Anoxia - complete loss of oxygen → complete blockage of blood flow. Quickly precedes cell death ● Reperfusion injury - AFTER blood flow returns ○ Cell injury causes inflammation → blood flow carries inflammatory mediators when reperfusing → damages tissue ○ Free radical and/or reactive oxygen species injury → free radical - any element with unpaired electron in outermost shell. Will try to bind to anything to steal another e- (common source of free radicals = oxygen) ■ Lipid peroxidation ■ Disruption of polypeptide chains ■ DNA damage HYPOXIC INJURY ○ Obstruction of blood flow → ischemia → decrease ATP → ■ decrease Na pump → (increase intracellular Na and Ca, extracellular K) → water goes into cell to balance Na/Ca → acute swelling → endoplasmic reticulum dilates → ribosomes detach (NEVER RETACH → mitochondria loses function) → lipid deposition ■ Increase glycolysis → increase lactate → decrease pH → swelling of lysosomes (lysosome digests. If it opens up = digestive properties in cell) ○ FREE RADICALS ○ Reactive oxygen species (memorize) ■ ■ ● Peroxidation of membrane lipids (reactive oxygen steals e- from lipids) can have numerous effects: ● Increased membrane rigidity ● Decreased activity of membrane-bound enzymes (ex. Na pump) ● Altered activity of membrane receptors ● Altered permeability ○ Formation of free radicals ■ Causes: UV light, metabolism, inflammation, ionizing radiation, smoking, air pollution ● Result: lipid peroxidation, DNA damage, disruption of polypeptides Cell adaptation to stress and injury ○ Manifestations of cell injury ■ Atrophy ● Cell # same, but smaller cells. All intracellular content decreased as well ■ Hypertrophy ● Cell # same, but cell size increases. Intracellular content increase ■ Hyperplasia ● Cell # increases, but cell size same ■ Metaplasia ● As a result of chronic injury ● As cells continue to get damaged and REPLACED, replacement is cell that is less mature than others. ■ Dysplasia ● PRECANCEROUS ● Complete derangement of self control over tissue ● Cell changes in BOTH size and number ● NOT ADAPTIVE. ■ Hypertrophy and hyperplasia → response to INCREASE IN FUNCTIONAL DEMAND ○ Ex. diabetes → pancreatic cells undergo hypertrophy so they can release more insulin ATROPHY Examples Atrophied liver cells (protein/calorie deficit) ● DECREASED FUNCTIONAL DEMAND ● DECREASED NUTRITIONAL SUPPORT ● ■ ■ ■ ■ ● HYPERTROPHY examples ● Increased functional demand ● Increased hormonal stimulation ○ Hyperplasia example ● ● ● ■ ● Metaplasia vs dysplasia ● ● ○ Increased functional demand Increased hormonal stim Chronic injury/tissue repair Metaplasia - replacement of terminally differentiated cell type with a less differentiated stem cell (terminally differentiated cell = lose ability to divide. Most functionally mature) ○ Ex. smoking ■ Leads to thick mucus ■ Difficulty coughing up mucus ● Bc squamous cells don’t function like regular cillia (less mature) → loss of function = pathology of problems ● Dysplasia ○ Rapidly dividing cells with risk of mutations Other manifestations of cell injury ■ Accumulations (or infiltrations) - cells store things inside itself. Problem happens when storing too much. ● 1. Cell cannot digest what it is presented (soot) → store it ● 2. Digestive enzymes deficient/immobilized ● 3. Cell is overwhelmed by demand to store ○ Water ○ Lipids ○ Lipid accumulation in liver cells ■ Examples ■ Brain with TAY-SACHS DISEASE ● Deficiency in enzyme needed to digest certain lipid → vacuoles store lipids → interferes with function of cell if too much ■ ● Fatty liver ● Hepatocytes of liver accumulate fat ○ Ex. alcohol consumption. Ethanol metabolized by liver creates acetyl aldehyde → a.a. Blocks liver ability to digest fat → chronic heavy drinking = liver enzyme levels elevated Irreversible cell injury ○ Necrosis ■ Coagulative necrosis - general tissue death ■ ■ ● Liquefactive necrosis ● Caseous necrosis ● Not liquefactive bc it has more connective tissue ○ Partially liquify ○ Present in lymph nodes that have been attacked/die as result of TB infection in lungs ■ ○ ○ Fat necrosis ● Necrosis in tissues high in fat (pancreas) ● When intracellular content of cells die and release → react with fatty deposit → SOAPORIFATION → soapy deposits in tissue (laziness) ● PROGRAMMED CELL DEATH ■ APOPTOSIS ● Conditions that trigger apoptosis: ○ Viral infection ○ DNA damage ○ Certain kinds of membrane/mitochondrial damage ○ Cell stress (Endoplasmic reticulum) ○ Induction of immune cells ○ WBCs instruct cells to apoptosis if ABNORMAL ■ If cell notices hella DNA mutations → apoptosis ●