Respiratory Failure. (Simplified version of Pathophysiology)

 Respiratory Failure

PKGhatak, MD

 Lungs are vital for survival. Disease, congenital abnormality, advanced age, or environmental condition produce changes in the structural and functional state of the lung to a degree that sustaining life becomes precarious and the condition is called respiratory insufficiency. When respiratory insufficiency, producing a low partial pressure of oxygen of arterial blood at or below PaO2 50 mmHg or partial pressure of arterial blood carbon dioxide PaCO2 of 50 mmHg or above, usually both at the same time, is known as respiratory failure.

Lack of Oxygen: It is widely understood that oxygen is essential for cellular respiration and normal bodily functions. Brain cells are particularly venerable to low O2, next are the heart, kidneys and liver.

Why CO2 accumulation is bad: CO2 when dissolves in the blood forms an organic acid CO2 + H2O = H2CO3. The H2CO3 immediately breaks down to  H2CO3 = H +HCO3. [H+] enters the cells (RBC) and K[+] is pushed out from the RBC into plasma and excreted in urine; the [HCO3-] combines with Na[+] inside the RBC and forms Na + HCO3 = NaHCO3. NaHCO3 reenters the plasma of blood. The enzyme carbonic anhydrase helps this reaction both ways. By this action, the blood manages to keep the pH at an optimal 7.4. When this Bicarbonate buffer system is overwhelmed by the rapid accumulation of CO2, two other blood buffers namely Phosphate buffer and Protein buffer try to maintain pH. The more CO2 accumulates the pH becomes lower and lower 7.3 ->  7.2->  7.1. And at this acid pH most cells function poorly and soon will die if the condition persists.

Effects of high CO2 in alveolar O2: Air entering the lung becomes fully saturated with water vapor. That means air pressure is 760-47 = 713 mmHg. The partial pressure of alveolar air O2, PAO2 is 20% of 713 = 160 mmHg. O2 is diluted further by CO2, as CO2 enters the alveoli from blood. Normal PaCO2 is 40 mm Hg. The O2 pressure now is 160 - 40 = 120 mmHg and arterial PaO2 is 110 mmHg (120 to 110) happens during the transition called A-a gradient. Oxygen saturation at PaO2 110 mmHg is 100 %.

In acute respiratory failure, assume that the CO2 is 70 mmHg, and the PAO2 will be 160-70=90 mmHg. At PAO2 90 mmHg arterial blood oxygen saturation is 87 %. That is hypoxemia. (the normal O2 saturation of arterial blood is 93 to 100 %).

 A simplified version of the lung is like a bellow seen in a blacksmith workshop. Lungs expand, taking in the fresh air and blowing out stale air by breathing out. Lungs are encased in an elastic box made up of vertebrae, ribs, intercostal and abdominal wall muscles and a muscular diaphragm. The respiratory center is situated in the hindbrain (actually three in number, inspiratory, exploratory in the medulla and pneumotactic center in the pons). The aortic body monitors O2, CO2 and pH of the blood and Carotid bodies monitor O2. The motor nerve for the diaphragm is the phrenic nerve, the neurons are situated in the cervical 4^th and a few in C3 and C5 spinal cord segments and spinal motor nerves for the respiratory muscles are supplied by the thoracic T1 to T12 and lumber L2 segments of the spinal cord.

The heart pumps blood to the lung alveoli to pick up oxygen before the oxygen can be distributed to all living tissues of the body and at the same time accumulated waste product of energy generation is carbon dioxide and which must to eliminated. Like a heat exchanger, the lung capillaries exchange CO2 of blood for O2 of the air in the alveoli. The transfer of gases is governed by laws of differential pressure gradient and solubility coefficient. O2 has a high affinity for hemoglobin and CO2 is forced out by an enzyme carbonic anhydrase.

Like a well lubricated machine, the airways of the lungs are kept moist and free of debris by mucus, and the airspace inside of the alveoli is kept open by surfactant. Any malfunction, of the above components or a combination of some of them, will cause respiratory insufficiency that may eventually lead to respiratory failure. Respiratory failure may develop suddenly as in strangulation or drowning called Acute Respiratory failure or after a prolonged period of an illness called Chronic Respiratory Failure as seen in pulmonary emphysema or kyphoscoliosis.

 Common causes of Respiratory Insufficiency that may lead to Respiratory Failure.

A. Chest wall: Multiple broken rib fractures and fracture of the sternum produce a frail chest wall limiting patients' ability to inhale. Pleurisy, herpes zoster and other painful chest wall pain can produce respiratory insufficiency. Severe spinal deformities, either congenital or acquired, usually lead to respiratory failure.

B. Reduced Space in the chest cavity: Massive pleural effusion, hemorrhagic effusion, empyema makes less space available for the lungs to expand.

C. Space occupying lesions: Thymoma, Lymphoma.

D. Loss of Lung volume: Pneumonectomy, pulmonary emphysema with bullous formation, pneumothorax, extensive cavitary disease of the lung.

E. Consolidation of lungs: Pneumonia specially in elderly in nursing homes. If pneumonia is bilateral, usually viral pneumonia like COVID, the alveolar surface area available for gas exchange becomes limited, accumulated secretion in the airways prevents normal air turnover in the lungs. That results in low O2 and accumulation of CO2 respectively.

F. Airway obstruction: Obstruction of the trachea by a foreign body, tumors, hemorrhage, large peritonsillar abscess.

G. Airway disease:  COPD, Asthma, cancers of main bronchus and trachea. These conditions produce limitations of air entry and exit in the lungs.

H. External pressure on major airways: Strangulation, invasive carcinoma of the thyroid gland.

I. Diseases of mucus and mucus clearance mechanism.: Cystic fibrosis, ciliary dyskinesia, bronchiectasis. Microorganisms flourish under those conditions, producing pneumonia and destruction of lung tissues.

J. Reduced capillary bed: Emphysema, recurrent pulmonary emboli, micro-platelet thrombi in covid, ATTP. Pulmonary fibrosis. These conditions prune surface areas of alveoli and capillaries making O2 transfer difficult.

K. Ventilation - Circulation Mismatch: a segment of the lung may have limitations of air entry due to airway disease or produce reduced blood circulation due to emboli, consolidation, or atelectasis. That will lead to wasted ventilation or transfer of O2.

L. Liquid filled alveolar space: Congestive heart failure, pulmonary edema, intrapulmonary hemorrhage, drowning. Air from the alveoli is pushed out by the liquids.

 M. Pump failure: Acute left ventricular failure, massive pericardial effusion, or traumatic pericardial effusion.

 N. Diseases of the nerves supplying respiratory muscles: Poliomyelitis, Gillian Berry syndrome, ascending polyneuritis. Succinylcholine intentional use. Botulinum poisoning. Paralysis of muscles that move the chest wall in and out results in ventilatory failure.

 O. Central nervous diseases: Respiratory centers are robust and keep functioning as long the blood supply to the respiratory center remains intact. Herniation of the brain from pressure following a massive brain hemorrhage, or removal of CSF by a spinal tap in inappropriate conditions. Opioid overdose.

An abnormal condition of alveolar capillaries, severe iron deficient anemia, emboli in the lung and pulmonary fibrosis, and loss of surface area of alveoli produce low arterial oxygen, whereas, under the same circumstances CO2 easily crosses from blood to alveolar air. That is because before any gas has to combine with hemoglobin or leave hemoglobin for the air in alveoli, that gas has to dissolve in the blood first. And CO2 is 160 times more soluble in blood than O2. The only way CO2 can accumulate in blood if the exchange of air in the alveoli lags behind. That is known as Ventilatory Failure. When a low O2 in arterial blood is present it is called Hypoxemia.

Respiratory Failure.

The common causes of Chronic Respiratory Failures are - advanced COPD, Pneumonia in chronic renal, hepatic, or cardiac failure and pneumonia in the elderly in debilitated conditions. In patients surviving more than 3 days with acute respiratory failure, the kidneys start generating bicarbonate and turn acute to chronic respiratory failure, into chronic respiratory failure. 

The common cause of Acute Respiratory Failure is – COPD with pneumonia, Narcotic overdose, sudden myocardial infarction, cardiac arrest and massive hemorrhage, and pulmonary edema.

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Near Drowning

 Near Drowning

PKGhatak, MD

Some drowning victims are rescued in time and revived by cardiopulmonary resuscitation (CPR). They are designated as Near Drowning.

  The World Health Organization reported 236,000 drowning deaths in 2019. Drowning is the 3rd leading cause of accidental death in the world. Many believe that the number is actually over 500,000 because of a lack of information from less developed countries.

  Submersion is when upper airways are underneath the liquid cutting off the air supply. Immersion is when the body is underneath the liquid and the upper airways are above the liquid maintaining an open path for air to reach the lungs. Both submersion and immersion generate a number of changes in the body, some are reflexes and others are biochemical and pathophysiological. Biological changes due to submersion are discussed here.

 Near Drowning may take place in warm water or cold water. The effects of water temperature have profound effects on the body.

 Diving Reflex.

 Disruption of air supply to the lungs in submersion causes a reflex attempt to breathe and a small amount of water enters the airway. That produces laryngospasm. The water in the airway immediately produces closure of the glottis. By these actions, further water entry into the lungs is prevented. The breath holding continues as long as the face is completely underwater. Subsequent events differ from warm water submersion and cold water submersion.

 The afferent nerve in the diving reflex is the sensory division of the Trigeminal and Glossopharyngeal nerves. The sensory information is related to the Nucleus Tactus Soliterious of the Vagus. The motor efferent action originates in the dorsal nucleus of the vagus and carries out by the recurrent laryngeal branch of the Vagus, and motor fibers of the Glossopharyngeal nerve. It results in the closure of the larynx and glottis,

 The autonomic efferent cholinergic fibers of the vagus to the heart originate in the nucleus ambiguous of the vagus and alpha1 fibers of sympathetic nerves to the artery and muscarine fibers of the vagus to the main pulmonary artery.

 Warm water submersion produces vasodilatation and hypotension; which result in sinus tachycardia and tachypnea.

 Coldwater submersion produces vasoconstriction and bradycardia, increases peripheral vascular resistance, reduces blood flow to muscles and proportionally increases blood flow to the brain due to cerebral hypoxia and hypercarbia.

 The respiratory center in the brain stem produces breath withholding as long as submersion continues. The aortic and carotid bodies sense hypoxia and produce vasoconstriction by alpha1 sympathetic nerves.

 Effect of Divining Reflex,

 Glottis closer prevents aspiration of water during submersion, slow heart rate decreases the oxygen demand of heart muscles. Increased arterial peripheral resistance decreases blood flow to muscles, lowering oxygen demand and redistribution of blood volume by increasing cerebral supply.

 Continued submersion produces cerebral anoxia, in spite of increased blood flow, and anoxia in vital neuronal centers results in the relaxation of muscles of the larynx and glottis, followed by water entry into the stomach and to the lungs. Underwater seizures may take place. Anorexic cerebral function loss is extensive, some are reversible others are not.

  Other injuries and effects of water submersion.

 Shallow water diving can produce fractures of cervical vertebrae, skull and ribs. Weeds and other vegetation may enter the mouth and throat. Fresh water in the lung alveoli washes away surfactant and leads to atelectasis. Saltwater pulls water from capillaries due to higher osmotic pressure and then destroys the surfactant. Atelectasis causes a mismatch of ventilation and circulation and increases intrapulmonary shunt. In general, about 100 to 200 ml of water entry in the lungs. That much water does not increase blood volume or electrolyte imbalance as previously thought, nor does significant hemolysis take place.

 Hypothermia is common and the core body temperature depends on the water temperature and duration of submersion. Effects on the heart in cold water submersion are sinus bradycardia, A-V nodal block, atrial tachycardia and atrial fibrillation; ventricular arrhythmias are less common. The cardiac arrest also happens.

 Bacteria, viruses and parasites are usually found in lakes and tanks. Various infections should be anticipated. Aspiration of gastric content happens during or after resuscitation and produces anaerobic pneumonia.

 Non-Cardiac Pulmonary Edema: In saltwater drowning hypertonic water draws water out of pulmonary capillaries and disrupts endothelial cells of alveoli capillaries. Plasma enters the alveolar space and pulmonary edema develops. The amount of seawater of 3 to 4 ml /Kg body weight can produce pulmonary edema,

 Cardiac collapse may develop after bringing the victim out of the water and cardiopulmonary resuscitation (CPR) started. In deep water drowning, water pressure around the thorax increases cardiac output. CPR increases cardiac output further causing cardiovascular collapse.

 CPR in Near Drowning is different from CPR for heart victims. The primary goal of CRP in Near Drowning is to correct hypoxemia as fast as possible and then correct other abnormalities deliberately paced and not so fast but are very vigilant and patients should be monitored continuously for cerebral hypoxia.

 Red Cross publicizes CPR instructions for the general public and provides advanced training for the first responders. CPR should be started as soon as the victim is brought to shallow water or on land by the rescuer and then call for help.

 No attempt should be made to drain water from the stomach. Those maneuvers only promote aspiration. Delay defibrillation because the carotid pulse is difficult to palpate on the cold and clammy skin of victims. Without an ECG (EKG) confirmation, no attempt should be made to diagnose asystole or VF (ventricular fibrillation), and the chilled heart does not respond properly to external electric jolts. Wet clothing should be removed and the body should be wrapped in a warm blanket.

 Warming the victim should only be done in hospitals equipped with extracorporeal heating and extrapulmonary membrane oxygenation facilities.

 All Near Drowning victims should be admitted to the hospital. Correcting hypoxia, hypercarbia, and acidosis in presence of cerebral anoxia calls for Pulmonary / Critical care specialists. One should not use PEEP (positive end respiratory pressure) without the input of PCWP (pulmonary capillary wedge pressure). Significant cerebral dysfunctions should be anticipated and addressed promptly and may require rehabilitation services upon discharge. Convulsion, hypoxia. Cerebral anoxia, hypotension, cardiac arrhythmia, pneumonia, and noncardiac pulmonary edema should be treated properly.

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