Pathophysiology of Pulmonary Disorders PDF

Pathophysiology of pulmonary disorders Prof. azza fekry 17-10-2024 1  Learning objectives of lecture Background of respiratory diseases. Common signs & symptoms. Pathophysiology of pulmonary disorders. Medical knowledge about: H...

Pathophysiology of pulmonary disorders Prof. azza fekry 17-10-2024 1  Learning objectives of lecture Background of respiratory diseases. Common signs & symptoms. Pathophysiology of pulmonary disorders. Medical knowledge about: Hypoxia, dyspnea(its scale) cyanosis, hyperventilation, hyperpnoea. Hypercapnia, sleep apnea( its types), Peripheral & central chemoreceptors. Kidney- lung relation ( acidosis & alkalosis). 2  Lung Diseases Overview Lung Diseases Affecting the Airways: Asthma, COPD, Chronic bronchitis, Emphysema. Acute bronchitis, Cystic fibrosis, Lung Diseases Affecting the Air Sacs (Alveoli): Pneumonia, Tuberculosis, Emphysema, Pulmonary edema, Lung cancer, ARDS, Pneumoconiosis. Lung Diseases Affecting the Interstitium: Interstitial lung disease, sarcoidosis, idiopathic pulmonary fibrosis, and autoimmune disease. Lung Diseases Affecting Blood Vessels: Pulmonary embolism(PE). Pulmonary hypertension. 3  Continue of respiratory diseases Lung Diseases Affecting the Pleura: Pleural effusion, Pneumothorax. Lung Diseases Affecting the Chest Wall: Obesity hypoventilation syndrome. Neuromuscular disorders. ( Amyotrophic lateral sclerosis and myasthenia gravis are examples of neuromuscular lung disease 4  Medical terms Hypoxia. Tachypnea. Cyanosis. Tachycardia. Bradypnea. Eupnoea. Dyspnea. Apnea Hyperventilation. Cheyenne-Stokes Hypercapnea. Kussmaul’s sign Hypoventilation. Sleep apnea. Hyperpnoea. 5  Symptoms of lung disease Breathlessness Feeling like you're not Coughing. getting enough air. Weight loss. Decreased ability to Fatigue. exercise. Wheezing. A cough that won't go A chest infection. away. Mucus production. Pain or discomfort when coughing up blood. breathing in or out. Chest pain. 6  Physiologic Median O2 Levels in Organs and Tissues hypoxia is associated with various pathophysiological conditions including chronic obstructive pulmonary disease, pulmonary hypertension, congenital heart disease, cerebral ischemia, and cancer. Defining Hypoxia States* Duration Extent Acute Hypoxia Low tissue oxygen from minutes to hours, due to ~ 1-2% O2 temporary limitations in blood flow Chronic Low tissue oxygen from hours to days, due to Anoxia limitations in the diffusion of oxygen to distant ~ 0.02% O2 and below tissues 7 What are the 4 types of hypoxia? For oxygen to make it to the cells in your tissues, you need: Enough oxygen in the air you breathe in. Healthy lung function to get oxygen to your alveoli. Healthy heart and circulatory functions to get oxygen- rich blood to your tissues. Enough red blood cells to deliver oxygen. Tissue cells capable of using oxygen. The four types of hypoxia are each caused by a lack of oxygen in any one of these areas. Hypoxemic hypoxia Low amounts of oxygen in the blood (hypoxemia) can lead to hypoxemic hypoxia, the most common cause of hypoxia. 8  Hypoxemia vs. Hypoxia Both terms refer to an insufficient Refers To amount of oxygen in the body Both conditions can result in fatal Result in damages Both can be diagnosed by measuring Diagnosis blood oxygen saturation Both are related to each other as Relation hypoxemia can cause hypoxia 9 10 Effects of Hypoxia on the Body: Hypoxia, if severe enough, can cause death of cells throughout the body, but in less severe degrees it causes principally: 1. Depressed mental activity, sometimes culminating in coma. 2. Reduced work capacity of the muscles. 3. confusion, restlessness, difficulty breathing, rapid heart rate, and bluish skin. 11 12 Effects of hypoxia on systemic and pulmonary circulation 13  How is hypoxia diagnosed? Pulse oximetry: Your healthcare provider places a sensor over your finger to measure the amount of oxygen in your blood. This procedure is noninvasive and painless. Arterial blood gas test (ABG) A thin needle is used to draw blood from your wrist, arm, or groin to check your oxygen levels. Pulmonary function test (PFT): You blow out and breathe in to a mouthpiece attached to a machine that measures how well your lungs work. Six-minute walk test (6MWT):You walk on a flat surface for six minutes to see how far you can walk in that time. This test helps your healthcare provider evaluate lung and heart function. Imaging: X-rays, CT scans, and V/Q scans all use special equipment to get images of your internal organs. Imaging can help your provider determine the cause of hypoxia. 14 Pulmonary Function Testing  Pathophysiology of Specific Pulmonary Abnormalities Hypoxia: Is deficiency in the amount of oxygen reaching the tissues. The following is a descriptive classification of the causes of hypoxia: 1. Inadequate oxygenation of the blood in the lungs because of extrinsic reasons as: a. Deficiency of oxygen in the atmosphere. b. Hypoventilation (neuromuscular disorders). 2. Pulmonary disease as: a. Hypoventilation caused by increased airway resistance or decreased pulmonary compliance. b. Abnormal alveolar ventilation-perfusion ratio (including either increased physiologic dead space or increased physiologic shunt). c. Diminished respiratory membrane diffusion. 16 3. Venous-to-arterial shunts (“right-to-left” cardiac shunts). 4. Inadequate oxygen transport to the tissues by the blood as: a. Anaemia or abnormal haemoglobin. b. General circulatory deficiency. c. Localized circulatory deficiency (peripheral, cerebral, coronary vessels). d. Tissue oedema. 5. Inadequate tissue capability of using oxygen as: a. Poisoning of cellular oxidation enzymes. b. Diminished cellular metabolic capacity for using oxygen, because of toxicity, vitamin deficiency, or other factors. 17  Cyanosis Cyanosis is a bluish discoloration of the skin, mucous membranes, tongue, lips, or nail beds and is due to an increased concentration of reduced hemoglobin (Hb) in the circulation. Clinically evident cyanosis typically occurs at an oxygen saturation of 85% or less. It is easier to identify under natural lighting and is typically more difficult to detect in patients with mild cyanosis, dark skin pigmentation, or anemia. Long-term complications of chronic cyanosis include clubbing, polycythemia, stroke, brain abscess, platelet abnormalities, lower-than-expected IQ, scoliosis, and hyperuricemia. 18 Hemoglobin (Hgb or Hb) is the primary carrier of oxygen in humans. Approximately 98% of total oxygen transported in the blood is bound to hemoglobin, while only 2% is dissolved directly in plasma. 19  PATHOPHYSIOLOGY Normally, there is ~ 2 g/dL of reduced (or deoxygenated) Hb in the circulation, and clinically evident cyanosis occurs when the concentration of reduced Hb reaches 5 g/dL. Therefore, the total amount of Hb is critical to the development of cyanosis. Oxygenated blood returns to the heart and is distributed throughout the body by way of the systemic vasculature. Oxygen is carried in the blood in two forms. Most oxygen in the blood is bound to hemoglobin within red blood cells, while a small amount of oxygen is physically dissolved in the plasma. 20 21 22 Hypercapnia (Excess Carbon Dioxide in the Body Fluids): CO2 retention is known as hypercapnia. Hypercapnia is usually due to hypoventilation or increased dead space in which the alveoli are ventilated but not perfused. In a state of hypercapnia or hypoventilation, there is an accumulation of CO2. The increased CO2 causes a drop in pH, leading to a state of respiratory acidosis. The chemoreceptor reflex is important in allowing the body to respond to changes in pO2, pCO2, and pH. 23 Chemoreceptors can be categorized as peripheral or central: Peripheral chemoreceptors Central chemoreceptors Positioned in the carotid and aortic Located near the ventrolateral bodies. surfaces of the medulla. Sensitive to changes in pCO2 and Sensitive to changes in mostly O2 pH. and CO2 and pH to a lesser degree. The glomus cells in the carotid and On the other hand, central aortic bodies detect states of chemoreceptors take longer to hypoxia, hypercapnia, and acidosis. detect a change in arterial pH On the other hand, central because H+ does not cross the chemoreceptors do not detect states BBB. of hypoxia. They detect a change in When a state of hypercapnia is introduced, central PCO2 very rapidly because CO2 chemoreceptor activity is increased. As a result, the sympathetic diffuses through the blood-brain outflow to the and barrier (BBB) vasculature into the is CSFincreased, and efforts are made to increase easily. the respiratory rate. 24  One might suspect, on first thought, that any respiratory condition that causes hypoxia would also cause hypercapnia. However, hypercapnia usually occurs in association with hypoxia only when the hypoxia is caused by hypoventilation or circulatory deficiency. The reasons for this are the following: Hypoxia caused by too little oxygen in the air, too little haemoglobin, or poisoning of the oxidative enzymes has to do only with the availability of oxygen or use of oxygen by the tissues. Therefore, it is readily understandable that hypercapnia is not a concomitant of these types of hypoxia. 25  In hypoxia resulting from poor diffusion through the pulmonary membrane or through the tissues, serious hypercapnia usually does not occur at the same time because carbon dioxide diffuses 20 times as rapidly as oxygen. If hypercapnia does begin to occur, this immediately stimulates pulmonary ventilation, which corrects the hypercapnia but not necessarily the hypoxia. Conversely, in hypoxia caused by hypoventilation, carbon dioxide transfer between the alveoli and the atmosphere is affected as much as is oxygen transfer. Hypercapnia then occurs along with the hypoxia. And in circulatory deficiency, diminished flow of blood decreases carbon dioxide removal from the tissues, resulting in tissue hypercapnia in addition to tissue hypoxia. However, the transport capacity of the blood for carbon dioxide is more than three times that for oxygen, so that the resulting tissue hypercapnia is much less than the tissue hypoxia. 26  When the alveolar Pco2 rises above about 60 to 75 mm Hg, an otherwise normal person by then is breathing about as rapidly and deeply as he or she can, and “air hunger,” also called dyspnoea, becomes severe. If the Pco2 rises to 80 to 100 mm Hg, the person becomes lethargic and sometimes even semi comatose. Anaesthesia and death can result when the Pco2 rises to 120 to 150 mm Hg. At these higher levels of Pco2, the excess carbon dioxide now begins to depress respiration rather than stimulate it, thus causing a vicious circle: 1. more carbon dioxide. 2. further decrease in respiration. 3. then more carbon dioxide, and so forth culminating rapidly in a respiratory death. 27 Clinical Significance: Patients with hypercapnia can present with tachycardia, dyspnea, flushed skin, confusion, headaches, and dizziness. If the hypercapnia develops gradually over time, symptoms may be mild or may not be present at all. Other cases of hypercapnia may be more severe and lead to respiratory failure. In these cases, symptoms such as seizures, papilledema, depression, and muscle twitches can be seen. If a patient with COPD presents with signs and symptoms of hypercapnia, immediate medical attention should be attained before CO2 reaches life- threatening levels. Hypercapnia should be managed by addressing its underlying cause. A non- invasive positive pressure ventilator may provide support to patients who are having trouble breathing normally. If a non-invasive ventilator is not efficient, intubation may be indicated. Bronchodilators may also be used in patients suffering from an obstructive airway disease. In recent studies, the use of the oesophageal balloon in managing hypercapnia in a patient with acute respiratory distress syndrome was also shown to be effective. 28 29 30 31 32 Related Testing: An arterial blood gas (ABG) is needed to evaluate patients with suspected hypercapnia. Hypercapnia is defined as the PaCO2 being greater than 42 mm Hg. If the PaCO2 is greater than 45 mm Hg, and the PaO2 is less than 60 mm Hg, a patient is in hypercapnia respiratory failure. 33 Dyspnoea: Dyspnoea means mental anguish associated with inability to ventilate enough to satisfy the demand for air. A common synonym is air hunger. At least three factors often enter into the development of the sensation of dyspnoea: (1) Abnormality of respiratory gases in the body fluids, especially hypercapnia and, to a much less extent, hypoxia. (2) the amount of work that must be performed by the respiratory muscles to provide adequate ventilation. (3) state of mind. 34  Grades of dyspnea (dyspnea scale): 35 Sleep Apnea: Sleep apnea is a chronic disorder that can occur in children or adults, and is characterized by the cessation of breathing during sleep. These episodes may last for several seconds or several minutes, and may differ in the frequency with which they are experienced. Sleep apnea leads to poor sleep, which is reflected in the symptoms of fatigue, evening napping, irritability, memory problems, and morning headaches. In addition, many individuals with sleep apnea experience a dry throat in the morning after waking from sleep, which may be due to excessive snoring. 36 Types of sleep apnea: Obstructive sleep apnea Central sleep apnea Caused by: an obstruction of the The respiratory centers of the airway during sleep, which can occur at brain do not respond properly different points in the airway, to rising carbon dioxide levels depending on the underlying cause of and therefore do not stimulate the obstruction. the contraction of the For example, the tongue and throat muscles of some individuals with diaphragm and intercostal obstructive sleep apnea may relax muscles regularly. excessively, causing the muscles to As a result, inspiration does push into the airway. not occur and breathing stops Another example is obesity, which is a for a short period. known risk factor for sleep apnea, as excess adipose tissue in the neck region can push the soft tissues towards the lumen of the airway, causing the trachea to narrow. 37 Hyperpnea: is an increased depth and rate of ventilation to meet an increase in oxygen demand as might be seen in exercise or disease, particularly diseases that target the respiratory or digestive tracts. Hyperventilation: is an increased ventilation rate that is independent of the cellular oxygen needs and leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH. 38  Kidney-Lung Relation Mutual Functions: Lung and kidney functions are intimately related in both health and disease. They work closely on:  The regulation of acid–base equilibrium (If the lungs or kidneys are malfunctioning, your blood’s pH level can become imbalanced.  Disruption in your acid-base balance can lead to medical conditions known as acidosis and alkalosis.  modification of partial pressure of carbon dioxide and bicarbonate concentration,  the control of blood pressure and fluid homeostasis  All closely depend on renal and pulmonary activities 39 Buffering (Acid-Base balance): The human body is built to naturally maintain a healthy balance of acidity and alkalinity. The lungs and kidneys play a key role in this process. A normal blood pH level is 7.40 on a scale of 0 to 14, where 0 is the most acidic and 14 is the most basic. This value can vary slightly in either direction. A buffer is a substance that can reversibly bind hydrogen ions. An acid is a molecule that releases hydrogen ions in solution. A base is a molecule that can accept a hydrogen ion. 40 Renal role: The kidneys have two very important roles in maintaining the acid–base balance:  They reabsorb bicarbonate from urine.  They excrete hydrogen ions into urine.  The kidneys are slower to compensate than the lungs, but renal physiology has several powerful mechanisms to control pH by the excretion of excess acid or base.  The major, homeostatic control point for maintaining a stable pH balance is renal excretion. 41 Lung Role: The lungs control your body’s pH balance by releasing carbon dioxide.  Carbon dioxide is a slightly acidic compound. It’s also a waste product produced by cells in the body as they use oxygen. The cells release it into your blood, and it’s taken to your lungs.  When you exhale, you’re expelling that carbon dioxide, a process that also helps regulate your body’s pH balance by reducing acidity.  The amount of carbon dioxide you exhale is a function of how deeply you inhale or exhale. Your brain constantly monitors this in order to maintain the proper pH balance in your body.  A blood pH imbalance can lead to two conditions: acidosis and alkalosis.  Acidosis refers to having blood that’s too acidic, or a blood pH of less than 7.35. Alkalosis refers to having blood that’s too basic, or a blood pH of higher than 7.45.  There are different types of acidosis and alkalosis based on the underlying cause.  When acidosis or alkalosis is caused by a lung disorder or issue with exhalation, it’s referred to as “respiratory.” When acidosis or alkalosis is caused by a problem with the functioning of the kidneys, it’s referred to as “metabolic.” 42 43 44 Lung dysfunction’s effect on acid-base: Respiratory acidosis: Respiratory acidosis is caused by your lungs not being able to remove enough carbon dioxide when you exhale. This can occur when your lungs are affected by a disease or other disorder. Some conditions that could lead to respiratory acidosis include:  Asthma.  Emphysema.  pneumonia (severe).  Respiratory acidosis can also be caused by taking narcotics or sleep medications. Brain and nervous system disorders that cause breathing problems may also lead to respiratory acidosis. 45 46  QUESTIONS Mention different types of lung diseases. Respiratory acidosis resulting from ( causes of it). Enumerate manifestation of lung diseases. Define each of the following: a) Hypoxia. b) Hyperventilation. Mention types of sleep apnea. Compare between resp. & metabolic alkalosis. Mention manifestation of hypercapnia. Can you explain the relation between lung & kidney in regulating acid-base balance. 47