Liver Failure and Hepatopulmonary Syndrome - Essay Example

Student name: Institution: Date: Liver failure is a condition that affects the proper functioning of the liver. It occurs when the liver is damaged beyond repair thus cannot accomplish its tasks appropriately. The liver is a vital organ in the body since it detoxifies chemicals and metabolizes drugs, it also produces bile and proteins responsible for blood clotting. However, cirrhosis and hepatitis can cause liver failure hence resulting in various symptoms such as hepatopulmonary syndrome and renal failure. Liver failure is characterised by such clinical symptoms as vomiting, jaundice, nausea, weight loss and fatigue (Friedman and Keeffe, 2012). Among the pulmonary conditions associated with chronic liver diseases are the hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). The frequency of HPS is patients is higher than that of POPH. Hepatopulmonary syndrome (HPS) refers to a syndrome characterized by shortness of breath and hypoxemia caused by the broadening of the blood vessels in the lungs of patients with liver disease (. According to the recent medical reports, HPS has been observed in 4-32% of adults with end stage liver diseases and in 9-20% of children. Hepatopulmonary syndrome comprises majorly of three components which include; liver disease, intrapulmonary vascular dilation and arterial hypoxemia (Kennedy et al., 1977). The liver disease, also called hepatitis has various causes. Liver disease is caused by viral hepatitides such as Hepatitis A and Hepatitis B viruses transmitted during child birth. Excess alcohol consumption can also cause liver diseases such as liver cancer, cirrhosis, alcoholic hepatitis and alcoholic fatty liver disease. The alcoholic liver disease begins with the accumulation of fatty acids in the liver caused by reduced fatty acids break down and increases the formation of triglycerides. As the disease progresses, it causes inflammation of the liver due to excess accumulation of the fatty acids. Scarring, caused by the body’s efforts to heal leads to cirrhosis. HPS occurs mostly in patients with cirrhosis and portal hypertension. The second component of HPS is the arterial hypoxemia that refers to the low concentration of oxygen in the arteries. Blood oxygen concentration is directly linked with the partial pressure of oxygen (PO2). The partial pressure of oxygen in the arterial blood reduces with advancing age and the minimum requirement for adults is 60mmHg. The importance of arterial hypoxemia in causing tissue hypoxia is critical. The arterial oxygen is utilized by the tissues of the body for the production of adenosine triphosphate (ATP) in a process called oxidative phosphorylation. Another component of HPS is the intrapulmonary vasodilation. It is a phenomenon in which the pulmonary arteries broaden in the presence of oxygen. Intrapulmonary vasodilation in patients can be detected by lung perfusion scanning, contrast echocardiography and pulmonary angiography. The two dimensional transthoracic contrast echocardiography is mostly used since it is more sensitive in detecting intrapulmonary vasodilation than perfusion scanning. Vasodilation refers to the increase in the diameter of the lumen of large arteries and veins caused by the relaxation of the muscular walls of these blood vessels. Vasodilation ensures that blood is supplied to all parts of the body. There are different mechanisms of vasodilation of the blood vessels. First is the temperature induced vasodilation. Exposure to cold, for example, causes the blood vessels to contract to minimising heat loss from the body. Exposure of a person to heat causes the blood vessels to dilate thus releasing the excess heat to the environment. Pulmonary vasodilation occurs as a result of the broadening of the pulmonary blood vessels. When vasodilation occurs in the arteries, the pressure of the blood in this vessels is reduced due to decreased vascular resistance. Vasodilation is important in the arteries since it reduces chances of hypertension. Therefore, heart conditions are treated using chemical arterial vasodilators. Dilation of the veins also reduces the blood pressure in the veins hence help in curbing cardiac output. One of the vasodilators in HPS is the nitric oxide, produced by the endothelial cells lining the blood vessels. The synthesis of nitric acid in the lungs is proliferated by the smooth muscle cells, vascular endothelium and the epithelial cells. Synthetically, the gas is produced by an enzyme called the NO synthase that combines oxygen with the amino acid L- arginine. The nitric oxide gas stimulates the solubility of guanylate cyclase, allowing conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP) that reduces intracellular calcium thus causing vasodilation. Another group of vasodilators in HPS are the prostacyclins such as prostaglandin I-2 and prostaglandin E-1. They are produced naturally as metabolites of arachidonic acid in the vascular epithelium. The prostacyclins help in the stimulation of the soluble adenylate cyclase in the vascular smooth muscle cells, thus converting adenosine triphosphate to cyclic adenosine monophosphate (cAMP). The protein kinases then causes a cAMP to induce a decrease in the intracellular calcium resulting in relaxation hence vasodilation. Nitric acid donors can also be administered to patients with vasoconstricted blood vessels to reduce the blood pressure in such vessels thus reduce hypertension. In this method, nitric acid is produced synthetically by the action of specified enzymes or spontaneously. The nitric oxide is delivered to the required site of the vascular smooth muscle where it facilitates vasodilation. Some nitric acid donor drugs administered to patients to help in vasodilation can also substitute nitric acid. An example is the sodium nitroprusside, a short term vasodilator used for the treatment of adverse hypertensive crisis. Ventilation is the movement of air between the atmosphere and the alveoli as well as its distribution within the lungs to maintain the required levels of oxygen and carbon dioxide in the blood (Kent, 2000). Ventilation is caused by inspiration and expiration. Contraction of the inspiratory muscles occurs as a result of the pressure difference between the airway and the alveoli, causing a reduction in the intrathoracic pressure. The alveoli then expand minimising the alveoli pressure and inspiration occurs. The pulmonary conditions that influence ventilation are pulmonary vascular engorgement, excess fluid in pleural space and obesity. The movement of blood through the pulmonary capillaries is called perfusion. Perfusion occurs in three major areas called zones of perfusion (Barash, 2009). Zone 1 is the alveolar dead space where there is no blood flow, blood flow occurs during systole in zone two while blood flows in zone three throughout the cardiac cycle. Blood from the heart moves to the lungs as pulmonary blood flow from the right ventricle. The sizes of pulmonary capillaries are smaller than the red blood cells. The gaseous exchange begins in the functional pulmonary capillaries. Since the alveoli are found within the network of pulmonary capillaries, the red blood cells spend about 0.75 seconds in the capillaries at rest and even less during exercise. The ventilation/ perfusion ratio is the ratio of the amount of air entering the alveoli and the quantity of blood that entering the lungs. The matching of ventilation and perfusion takes place at the alveolar capillary level. Ventilation/perfusion mismatch occurs when there is an imbalance between the blood flow and the alveoli air flow. An increase in the V/Q ratio result in the formation of the alveoli dead space, resulting in pulmonary emboli, vasoconstriction of the pulmonary blood capillaries, tumours and collapse of the alveoli. An alveolar dead space is described as an area in the respiratory tract where there is gaseous flow with inadequate circulation for gaseous exchange (Barash, 2009). Fig 1: showing ventilation and perfusion mismatch in hepatopulmonary patients Source: downloaded from www.pintrest.com From the above diagram, alveolar ventilation and pulmonary blood flow in a healthy person are uniform, hence allowing the efficient diffusion of oxygen in the blood vessels as shown in the first panel. The second panel shows ventilation/perfusion mismatch in patients with hepatopulmonary syndrome. The blood capillaries are dilated thus causing lack of uniformity in blood flow. Diffusion of oxygen into the tissues is hence reduced. A decrease in the V/Q ratio causes intrapulmonary shunting. The occurrence of an intrapulmonary shunt is associated with considerable alveolar hypoventilation in relation to normal perfusion. As a result. Low oxygen concentrated blood returns to the left heart causing oxygenation problems. The lungs of normal people with uniform ventilation and perfusion have capillary diameter sizes ranging from 8to 15micrometres, allowing efficient oxygen diffusion in the vessel hence a perfect balance between ventilation and perfusion. Arteriovenous shunting is the creation of an abnormal connection between an artery and a vein. It can either be congenital or can result from surgery. Also called arteriovenous fistula, this condition allows the exchange of blood between the veins and arteries involved without having to pass through the capillaries (Lanzer and Topol, 2002). For small arteries and veins, this shunting does not create many problems. However, for larger blood vessels, the connection is problematic and must be corrected through surgery. Arteriovenous shunts cause clinical symptoms such as the swelling of veins that appear similar to varicose veins. It can also cause fistula in the lungs thus requires urgent treatment. Patients diagnosed with the hepatopulmonary syndrome, however, have many dilated capillaries thus causing a non-uniform blood flow. It causes ventilation/ perfusion mismatch as a primary clinical manifestation. The ultimate result is decreased diffusion of oxygen into these blood vessels that can cause tissue hypoxia. The causes of ventilation and perfusion mismatching are uneven resistance to airflow caused by inflammation, collapsed airways and constriction of the bronchioles as well as the lack of uniform compliance in the lungs caused by pulmonary vascular congestion, fibrosis and atelectasis. Hepatorenal syndrome refers to the renal failure in patients with portal hypertension. The condition occurs specifically in the kidney, where glomerular infiltration is reduced and tubular reabsorption and urine concentration is increased by regulatory mechanisms, hence causing uraemia (Friedman and Keeffe, 2012). The syndrome is observed mostly in patients with ascites. There are two different types of Hepatorenal syndrome. Type 1 HRS is caused by the reduction in the effective circulating volume resulting from splanchnic arterial vasodilation and reduced cardiac output. Type 2 HRS is caused by sow progression of renal failure such that the primary clinical manifestation is refractory ascites rather than acute renal failure. The therapeutic treatment for Hepatorenal syndrome is a liver transplant. The eligibility of patients for liver transplants differ. Ineligible patients can be treated using terlipressin plus albumin. The recovery of the renal functions can be achieved in less than 50% of patients and the problem can reoccur in patients who have been responding well to treatment. Hepatic portal hypertension is a condition caused by the increased blood pressure within a system of veins called the portal venous system that leads to the liver. It is caused by chronic liver diseases, structural changes that causes increased hepatic resistance and increased portal venous blood flow as well as obstruction of blood flow in the veins. Undisturbed vascular channels are smooth. Cirrhosis, however, makes the vascular channels irregular and rough thus causing a resistance to blood flow. The result is increased pressure causing dilation of the veins and their tributaries. The portal system pressure is characterized by the input from the blood flow in the portal vein and the resistance of the hepatic system to the outflow of blood (Humbert et al., 2013). The portal vein pressure exceeds the vein- free hepatic pressure by 4mmHg and the right arterial pressure by 6mmHg. Pressures beyond these limits characterize hypertension. The primary symptom of hepatic portal hypertension is gastrointestinal bleeding in the early stages. However, patients with adverse liver conditions present ascites, jaundice, hepatic encelophalopathy and spider angiomata. Hepatic portal hypertension is caused by suprahepatic abnormalities such as inferior vena cava thrombosis or webs, cardiac diseases and hepatic etiology. Alteration of the portal blood flow is also a major cause of hypertension. It is also known to be caused by cytokines such as tumour necrosis factor alpha that stimulates endothelial vasodilators such as nitric oxide and prostacyclin as well as non-endothelial vasodilators such as glucagon. The splanchnic circulation comprises of the gastric, intestinal, colonic, pancreatic, spleen and hepatic circulation in a parallel arrangement. The blood from the gut, pancreas and the spleen flows into the hepatic system through the portal vein (Pinsky et al., 1995). The blood then flows through the liver sinusoids, re-entering the systemic circulation through the hepatic veins. The splanchnic circulation is important since it allows the removal of harmful bacteria by the reticuloendothelial system of the sinusoids. Splanchnic blood flow is influenced by the normal blood circulation, degree of collateral blood flow and exposure to exogenous and endogenous neuro-humoral factors. Normal splanchnic blood circulation is important in immune function, nutrient absorption and maintenance of intestinal motility (Pinsky et al., 1995). The intrinsic factors that influence splanchnic circulation are metabolic and myogenic factors. For instance, accumulation of metabolites during hypoxia causes vasodilation this restoring blood flow. When the oxygen supply is increased in the tissues, vasoconstriction occurs. The extrinsic factors that affect splanchnic blood flow are the autonomic nervous system and circulating vasoactive substances. The splanchnic circulation comprises of three arteries; the coeliac artery that is the primary blood supply to the stomach, upper duodenum, the spleen and the pancreas, the superior mesenteric artery that supplies blood to the lower duodenum, ileum, colon, caecum and appendix and the inferior mesenteric artery that supplies blood to the upper rectum and descending colon. The development of the Hepatorenal syndrome is explained by the underfill theory. The underfill theory suggests that formation of ascites occurs as a result of a threshold of imbalance in the Starling’s forces across the splanchnic and hepatic beds. Consequently, increases amounts of lymph is produced exceeding the capacity of the thoracic cavity for its return to the systemic circulation (Gerbes 2011). It explains that ascites associated with renal hypertension causes hypovolemia thus minimising the portal pressure and the retention of sodium and water. The increased sodium concentration causes a rise in the portal pressure and the plasma volume. Underfill is also caused by the low systemic vascular resistance in patients with cirrhosis and ascites. The low resistance is associated with the formation of systemic arteriovenous shunts and resistance vessel vasodilation caused by the circulating vasodilators. The effective plasma volume is reduced by this combination of the physical and haemodynamic factors (Kuntz, 2008). The low effective blood volume stimulates the sympathetic nervous system, activates the renin- angiotensin- aldosterone system hence increased renal sodium and water retention. The abnormal accumulation of fluids in the abdominal cavity is called ascites. Patients with cirrhosis often develop ascites at some stages of the disease. Ascites formation is caused by changes in the hepatic and intestinal lymph formation as well as changes in the ability of the kidney to handle sodium (Gerbes, 2011). Hepatic sinusoidal hypertension results in increased formation of lymph. Intrahepatic hypertension causes increased portal pressure thereby helping in fluid collection in the peri-toneal cavity. Patients with cirrhosis have an increased return rate of the lymph though the thoracic duct compared with the normal patients (Barash, 2009). The lymphatic return through the thoracic duct in cirrhosis is five times greater and may reach 20 litres in a day for cirrhosis patients with ascites. The two major theories that have been used to explain the development of ascites are the underfill and the overflow theories. The overflow theory suggests that the formation of ascites is due to retention of sodium by the kidneys leading to increased fluid retention hence increased plasma volume that overflows into the extravascular space. The evidence that is used in the support of this theory is that patients with cirrhosis have lower plasma renin activities and aldosterone levels compared to the normal individuals. Ascites is a common clinical problem in most patient with liver cirrhosis and is a leading sing of portal hypertension (Gerbes, 2011). The clinical diagnosis of ascites in hepatorenal syndrome involves assessing the protein concentration and granulocyte counts in the patients’ blood. Sodium restriction and diuretics are used in the management of ascites, although additional therapy is offered to patients that are not responsive to these modes of treatment. Hepatorenal syndrome and hepatopulmonary syndrome are dangerous diseases of the liver that affect the respiratory system. If not properly checked, these diseases can cause permanent malfunctioning of the liver hence leading to transplants through surgery. Healthy living, therefore, requires that the consumption of alcohol, which is a primary cause of cirrhosis, be reduced to enable proper functioning of the renal system. References Barash, P. G. (2009). Clinical anaesthesia. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. Falk Symposium, Gerbes, A. L., & Paumgartner, G. (2001). Hepatology 2000: Symposium in honour of Gustav Paumgartner: proceedings of the Falk Symposium 117 held in Munich, Germany, May 4-6, 2000. Dordrecht: Kluwer Academic. Friedman, L. S., & Keeffe, E. B. (2012). Handbook of liver disease. Philadelphia, PA: Elsevier/Saunders. Gerbes, A. L. (2011). Ascites, hyponatremia, and hepatorenal syndrome: Progress in treatment. Basel: Karger. Handler, C. E., & Coghlan, G. (2012). Pulmonary hypertension. Oxford: Oxford University Press. Humbert, M., In Evgenov, O. V., & In Stasch, J.-P. (2013). Pharmacotherapy of pulmonary hypertension. Kent, M. (2000). Advanced biology. Oxford: Oxford University Press. 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