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 hemoglobin
2. 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
didnt 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 dont 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 Fever
o 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 wood
Alcohol 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 youre 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 decreased
Anemia 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 dont 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