Objectives  Types and causes of therapy and toxicity  Definition, causes and factors affecting Hypoxia

 Definition: O2 deficiency at the tissue level . Anoxia: absence of O2 (is not possible in the body during life)  Types of hypoxia 1) Hypoxic hypoxia

. PaO2 2) Anemic hypoxia

. Normal PaO2, Hb. 3) Stagnant or ischemic hypoxia

. Normal PaO2 & Hb, blood flow 4) Histotoxic hypoxia

. Normal PaO2 , Hb & blood flow,  oxidative enzymes

Causes: Hypoxic hypoxia (most common case of hypoxia)

1)  PO2 of inspired air . High altitude. 2) Hypoventilation . Respiratory center (depression) . Nerves (myesthenia gravis) . Muscles (myopathy) . Thoracic cage (kyphosis, scoliosis) . (obstructive & restrictive lung diseases) 3) Alveolo-capillary block . Pulmonary congestion, fibrosis, and edema 4) Disturbed V/Q ratio . Collapse, pneumonia, 5) Shunting venous to arterial blood Anemic hypoxia 1) Quantitative: . Anemia 2) Qualitative: . CO & metHb Stagnant hypoxia 1) Generalized: . CCF . Shock. . Polycythemia. 2) Localized: . Thrombosis, embolism. . Vascular spasm Histotoxic hypoxia 1) Cytochrome oxidase . Cyanide 2) Dehydrogease . Alcohol, narcotics Hypoxia & cyanosis

Normal Hypoxic Anemic Stagnant Histotoxic All N PO 100  2 N N N O2 19.8    N N arterial     % 97%  N N N

   PO2 40 ↑  O2 15.2    ↑ % 75%    Venous        ↑

No Cyanosis  No  red hypoxia Chemical Chemical Chemical Chemical O2 therapy ↑ Physical ↑ Physical ↑ Physical ↑ Physical ↑ CO poisoning red hypoxia

1) HbO2  HbCO (same site of O2 binding) 2) Shift O2-Hb dissociation curve to the left. 3) Affinity of Hb to CO is 230 times that of O2 4) Dissociate slowly from Hb.  Symptoms 1. Red (HbCO-red cherry color) 2. Respiration is not stimulated 3. Death (70% carboxy-Hb) headache, nausea &  judgment.  Treatment 1. Terminatation of exposure. 2. Artificial respiration. 3. 95% O2 + % CO2 4. Exchange blood transfusion

Met-Hb (bluish)  Another cause of anemic hypoxia  Caused by oxidizing agents Sulph-Hb (bluish)  Another cause of anemic hypoxia (rare)  Caused by exposure to sulfur compounds (drugs or occupational)

Oxygen therapy  Highly useful . Hypoxic hypoxia (except venous to arterial shunt) . CO poisoning  Less useful anemic and stagnant hypoxia  Not useful histotoxic hypoxia Oxygen toxicity

 Free O2 radicals damage (oxidative enzymes & nervous symptoms)

 Pure O2 . 8 hours: irritation of upper respiratory tract . 24-48 hours: damage to the lung .  48 hours: CNS symptoms  In premature infant may cause blindness (↑ O2 in eye vessels  vasoconstriction of retinal blood vessels) retinal fibrosis

 Hyperbaric O2 accelerate onset of toxicity . Useful in CO poisoning and gas gangarene (anerobic bacteria)

Cyanosis  Definition: bluish discoloration of skin and mucous membrane due to reduced Hb in capillary (5g/100ml)  Cause:

. Hypoxic hypoxia and stagnant hypoxia (PO2) . Asphyxia (PO2, PCO2 & acidosis)  Relation to hypoxia . Absent in anemic hypoxia & histotoxic hypoxia  Types of cyanosis . Generalized . Localized (peripheral)  Factors affecting cyanosis . Skin: thickness (clear in thin skin e.g. lips) and pigmentation (less clear in dark skin individual) . Capillary: direct proportional to blood flow . Hb: total (polycythemia, anemia), reduced (metHb, sulf-Hb), abnormal (lipemia)

Asphyxia  In asphyxia (occlusion of the airway), acute hypercapnia and hypoxia develop together → pH drop.  Pronounced stimulation of respiration, with violent respiratory effort.  ↑Catecholamine secretion → ↑Blood pr & HR.  Eventually the respiratory efforts cease, the blood pr and HR  (asphyxiated animals can be revived at this point by artificial respiration).  If artificial respiration is not started, cardiac arrest occurs in 4- 5minutes.  Drowning is suffocation by immersion (water).  In 10% of drowning, the first gasp of water after losing struggle not to breathe triggers laryngospasm, and death result from asphyxia without any water in the .  In 90% the glottic muscles eventually relax and fluid enters the lungs.