Goljan Live Notes Day 1

Hypoxia – inadequate oxygenation of tissue

Oxygen for oxygenation phosphorylation in mitochondria pathway ETC, last reaction is oxygen is an electron acceptor. Protons are being kicked off the electron transport system, going back to the membrane to form ATP.

ATP is mainly generated in the mitochondria

What carries oxygen? Hemoglobin is the most important times the oxygen saturation plus partial pressure of arterial oxygen

Hemoglobin – O2 to heme group saturation of O2 and partial pressure of arterial oxygen

O2 content – hemoglobin times O2 saturation plus Arterial Oxygen

Partial Pressure of oxygen – Amount of oxygen dissolved in plasma

Iron has to be plus 2 to carry oxygen

If all 4 heme groups are occupied with red blood cells and oxygen the saturation is 100 percent

The oxygen flows in the following direction 1. Alveoli – diffuses through the red blood cell membrane and attaches to the

heme group on red blood cell on the hemoglobin2. If the partial pressure of oxygen decrease, o2 saturation is decreased as well

When you retain CO2 – respiratory acidosis, P02 goes down CO2 high = PO2 low

Acidosis = CO2 = PO2 down hypoxemia

Ventillation defect = RDS – Hyaline membrane Disease No ventilation, but there is perfusion Recognize on exam – patient on hypoxemia and given 100% oxygen but PO2

didn’t increase because there is a shunt. Intrapulmonary Shunting

Perfussion defects – pulmonary embolis – prolong flights. Stasis from immobilization Increases the dead space Given 100% oxygen PO2 goes up!

Diffusion Defect – Fibrosis halts oxygen transportation

Pulmonary Edema – fluid restricts oxygen movement Cardiac Failure – fluid restricts the transportation of oxygen to vital regions Fluid in interstitial of the lung causes irritation to the J receptors causing

dyspnea

Anemia – Oxygen Content?

Decreased Hemoglobin, Normal Respiration – P02 normal O2 saturation is normal

Tissue hypoxia = exertional dyspnea – exercise intolerance

Carbon Monoxide – a heater in a wintertime, room heaters have combustible material and inhaling can cause CO2 poisoning. House fire is another big cause of CO2 poisoning. Another house fire related is cyanide poisoning from the insulation.

People in housefires have both cyanide and CO2 poisoning.

Co2 very high affinity for hemoglobin and highly diffusible, O2 saturation goes down because CO2 is very high affinity to hemoglobin. It dissociates O2 from the heme region because CO2 is taking up space on the HEME group. O2 saturation is down. Treatment is 100% oxygen which increases O2 saturation.

Decrease of oxygen saturation = cyanosis. Why don’t we see that in CO2 because cherry red appearance masks it. The most common symptom is headache.

Methhemaglobin – its iron in plus 3 state, oxygen cannot bind to it. Oxygen saturation is decreased, chocolate colored blood because no O2 on heme groups. The P02 is normal, the hemoglobin is normal.

RBC – methemoglobin reductase system – convert Fe iron in plus 3 state back to plus 2 state.

Nitrites and Nitrates in drinking water are oxidizing agents, which oxidizes hemoglobin and iron to plus 3 state, which causes methemoglobinemia, treatment is IV blue.

Dapsone – sulfur and nitro drugs – produce methemoglobin and potential to increase G6PD and hemolytic Anemia, oxidizing agents causing increase in peroxide which destroys RBC.

Methemoglobenemia with HIV – Treatment Pneumocystis carinii potential side affects is methemoglobenemia

Right shift curve – Hemoglobin with decrease affinity to oxygen, what moves the curves to the right 2-3 BPG

o Fevero Low Ph o High altitude – right shift curve, resp alkalosis, hyperventilate o Decrease CO2 – respiratory alkalosis = right shift because of high

altitude causes increase of 2-3 BPG

Left Shift CO2 Methemoglobin Decrease 2-3BPG Alkalosis

Cytochrome Oxidase – last enzyme before it transfers the electron to the oxygen electron acceptor Cyanide and CO2 inhibit Cyctochrome Oxidase

Uncoupling – ability for the mitochondria to synthesize ATP – Inner mitochondrial membrane is permeable to protons, ATP synthase carrier is where proton is suppose to travel to form ATP.

Dinitrophenol – chemical to preserve woodAlcohol – protons to go right through the membrane and very little ATP generation

Uncoupling agents – protons leaking out of the membrane pores without going through the ATP synthase so there is no generation of ATP and therefore the decrease of ATP causes severe energy depletion in the human body, all the reactions start increase to make more NADPH and more electron transport chain to produce more protons, the body can go into hyperthermia as compensation.

If you’re an alcoholic on a hot day increases chances of heat stroke, because alcoholics are so susceptible to heat stroke because they are already having uncoupling agents destroy the mitochondria and therefore are very susceptible to heat stroke.

Respiratory Acidosis – hemoglobin is normal, oxygen saturation and PO2 decreased Partial pressure of oxygen in arterial decreasedAnemia – Oxygen saturation and PO2 is normal only hemoglobin conc is decreased CO2 and Methemoglobenemia – O2 saturation affected decreased, Hemoglobin is normal and P02 is normal. Treatment – 100% 02 for C02 and IV blue for Methemoglbenemia and ascorbic acid.

Decrease in ATP – tissue hypoxia – Anaerobic Glycolysis triggered, end product is Lactic Acid.

Pyruvate is converted to Lactic Acid due to increase in NADH.

Need to make NAD for feedback in the glycolytic cycle to make 2 more ATP

Mitochondria makes all ATP, one place where you can get 2 atp without going to mitochondria is anaerobic glycolysis without oxygen.

Mitochondrial system shutdown – anaerobic glycolysis forms only 2 ATP causes buildup of Lactic Acid and increase anion gab metabolic acidosis, within a cell it causes denature protein due to increase in acid. Denaturing is altering its configuration and in terms of enzymes its denatured as well. The cell cant autodigest itself because of buildup of enzymes and is caused coagulation necrosis.

Coagulation Necrosis Gross Infarction through buildup of acid in the cell which denatures the structure and enzymes of the cell. The ATPase pump is broken and Na/K pump is ineffective in anaerobic glyclosis, Na comes into the cell and causes cellular swilling because water comes into the cell with sodium

This is a reversible injury. Cellular swelling because of tissue hypoxia causes sodium potassium pump causes sodium and water to into the cell and causes reversible injury. Adding oxygen will remove sodium and bring cell back to natural healthy state.

In mature red blood cells don’t have mitochondria, so normally have anaerobic glycolysis is always going on.

a cell without o2 is going to cause irreversible injury Biggest agents is calcium, activates phospholipases in cell membrane and

causes damage to cell membrane Activates enzyme in nucleus causes pyknosis and nuclear chromosome

disappears Goes into mitochondria – destroys the mitochondria Hypercalcemia produces acute pancreatitis, activate pancreas enzyme. Cell membrane damage is hallmark of irreversible damage, mitochondria the

energy producing factory destroyed is also irreversible.

Free radical injury – Brownish Pigment in older people organ called atrophy lipufushcin.

When you have free radical damage end product is lipufuschin, unbreakable lipid.

what is a free radical? A compound that has an unpaired electron