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University of Manitoba
Biochem. and Medical Genetics
BGEN 3020
Jason Leboe- Mcgowan

CHAPTER 1: CELLULAR REACTION TO INJURY Key issues – hypoxia, cyanide poisoning, free radicals, apoptosis, growth alternations (i.e. hypertrophy, atrophy, hyperplasia, etc…) I. Hypoxia = inadequate oxygenation of tissue (same definition of as shock). Need O for oxidati2n phosphorylation pathway – where you get ATP from inner Mito membrane (electron transport system, called oxidative phosphorylation). The last rxn is O to r2ceive the electrons. Protons are being kicked off, go back into the membrane, and form ATP, and ATP in formed in the mitochondria A. Terms: 1. Oxygen content = Hb x O satn 2 partial pressure of arterial oxygen (these are the 3 main things that carry O in our blood) 2 In Hb, the O attaches to heme group (O sat’n) 2 2 Partial pressure of arterial O i2 O di2solved in plasma In RBC, four heme groups (Fe must be +2; if Fe+ is +3, it cannot carry O ) 2 Therefore, when all four heme groups have an O on it, the O sat’n is 100%. 2 2 2. O sat’n is the O IN the RBC is attached TO the heme group = (measured by a pulse 2 2 oximeter) 3. Partial pressure of O is2O dis2olved in PLASMA O 2low: from alveoli through the interphase, then dissolves in plasma, and increases the partial pressure of O , diffuses through the RBC membrane and attaches to the heme groups on the 2 RBC on the Hb, which is the O sat2n Therefore – if partial pressure of O is2decreased, O sat’n2HAS to be decreased (B/c O came 2 from amount that was dissolved in plasma) B. Causes of tissue hypoxia: 1. Ischemia (decrease in ARTERIAL blood flow ……NOT venous) MCC Ischemia is thrombus in muscular artery (b/c this is the mcc death in USA = MI, therefore MI is good example of ischemia b/c thrombus is blocking arterial blood flow, producing tissue hypoxia) Other causes of tissue ischemia: decrease in Cardiac Output (leads to hypovolemia and cardiogenic shock) b/c there is a decrease in arterial blood flow. nd 2. 2 MCC of tissue hypoxia = hypoxemia Hypoxia = ‘big’ term Hypoxemia = cause of hypoxia (they are not the same); deals with the partial pressure of arterial O 2O d2ssolved in arterial plasma, therefore, when the particle pressure of O is decrea2ed, this is called hypoxemia). Here are 4 causes of hypoxemia: a. Resp acidosis (in terms of hypoxemia) – in terms of Dalton’s law, the sum of the partial pressure of gas must = 760 at atmospheric pressure (have O , CO , a2d nit2ogen; nitrogen remains constant – therefore, when you retain CO , this 2s resp acidosis; when CO goes up, 2 pO 2AS to go down b/c must have to equal 760; Therefore, every time you have resp acidosis, from ANY cause, you have hypoxemia b/c low arterial pO ; increase CO = decrease pO , and vice versa in resp alkalosis). 2 2 2 b. Ventilation defects – best example is resp distress syndrome (aka hyaline membrane dz in children). In adults, this is called Adult RDS, and has a ventilation defect. Lost ventilation to the alveoli, but still have perfusion; therefore have created an intrapulmonary shunt. Exam question: pt with hypoxemia, given 100% of O for 20 m2nutes, and pO did not 2 increase, therefore indicates a SHUNT, massive ventilation defect. c. Perfusion defects – knock off blood flow MCC perfusion defect = pulmonary embolus, especially in prolonged flights, with sitting down and not getting up. Stasis in veins of the deep veins, leads to propagation of a clot and 3-5 days later an embolus develops and embolizes. In this case, you have ventilation, but no perfusion; therefore there is an increase in dead space. If you give 100% O for a 2 perfusion defect, pO wi2l go UP (way to distinguish vent from perfusion defect), b/c not every single vessel in the lung is not perfused. Therefore, perfusion defects because an increase in dead space, while ventilation defects cause intrapulmonary shunts. To tell the difference, give 100% O and see 2hether the pO 2 stays the same, ie does not go up (shunt) or increases (increase in dead space). d. Diffusion defect – something in the interphase that O cannot2get through…ie fibrosis. Best example–Sarcoidosis (a restrictive lung disea
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