Blood Coagulation
Blood coagulation involves the activation of various factors in the blood. There are two coagulation pathways. The first is the intrinsic pathway that begins in the circulation and is initiated by activation of circulating factor XII. The extrinsic pathway is activated by cellular lipoprotein called tissue factor that is exposed when the tissues are injured. Both pathways lead to the activation of factor X which activates the conversion of prothrombin to thrombin which activates the conversion of fibrinogen to the insoluble fibrin threads that hold the clot together (Porth, 2007).
Clot Retraction
Minutes after the clot is formed, the actin and myosin in the platelets are trapped in the clot and begin the contract like the vessel walls do in vessel spasm (Porth, 2007). During the contraction, the fibrin strands of the clot are pulled toward the platelets. This process squeezes the serum which is the plasma from the clot and causes it to shrink.
Clot Dissolution
The clot begins to dissolve shortly after it is formed. This process begins with the activation of plasminogen which is an inactive precursor of the proteolytic enzyme; plasmin. Large amounts of plasminogen are trapped in the clot when it is formed. The powerful activator called tissue plasminogen activator (t-PA) is slowly released from the injured tissues (Porth, 2007). This converts plasminogen to plasmin that digests the fibrin strands and causes the clot to dissolve.
The liver, plasma and endothelium of the vessel are the major sources of the physiologic activators. These activators are released due to vasoactive drugs, exercise and body temperature. The
Liver Failure 8
activators are unstable and rapidly inactivated by inhibitors like plasminogen activator inhibitor – 1 that is made by the liver and the endothelium. Chronic liver disease, for this reason, may cause altered fibrinolytic activity. This can lead to easier clot formation causing heart attacks or deep vein thrombosis (Kohler & Grant, 2000). Bleeding can also occur due to a decrease in platelets with the most commonly affected area of the body involving the gastrointestinal (GI) and genitourinary (GU) tract. Coagulation
factors like V, VII, IX, X, XI and XII, prothrombin and fibrinogen are synthesized in the liver. In liver disease, synthesis of these clotting factors is reduced and bleeding may result (Lisman & Leekek, 2007). The syntheses of these clotting factors are reduced due to lack of vitamin K. Vitamin K deficiency can be caused by liver disease. The presence of vitamin K is required for normal activation of these coagulation factors. Vitamin K is a fat soluble vitamin that is continuously being synthesized by intestinal bacteria, however, in liver disease absorption of vitamin K is impaired. The liver produces the clotting factor in an inactive form resulting in a possible GI and/or a GU bleed (Lisman & Leebek, 2007).
Manifestations
of Liver Disease
Two common manifestations of liver disease are ascites and hepatic encephalopathy. Ascites is an accumulation of fluid in the peritoneal cavity, and hepatic encephalopathy is a complex neurologic syndrome characterized by impaired cognitive function, flapping tremor, and EEG changes (McCance & Huether, 2006). Of the two manifestations the pathophysiology of ascites is better understood, but research is ongoing to determine the pathophysiology of hepatic encephalopathy.
Ascites
occurs as a result of several factors.
It is the result of pressure in the hepatic veins rising as little as
3-7 mm Hg above normal (0 mm Hg), which causes excessive amounts of fluid to
leak into the abdominal cavity (Guyton & Hall, 2006). The rise of pressure is
partly caused by the large amounts of fibrous tissue (caused by cirrhosis) in
the liver which impedes the flow of blood through the liver raising capillary
pressure (Guyton
& Hall, 2006).
Vasodilatation occurs due to an imbalance of
vasoactive substances favoring vasodilators. This causes a decrease in
effective circulating blood
volume,
which is perceived as hypovolemia. This causes the activation of various
vasoconstrictor systems, including the renin-angiotensin-aldosterone system,
the sympathetic nervous system, and arginine vasopressin, producing renal
vasoconstriction with an increase in renal sodium and water reabsorption, as
well as a decrease in glomerular filtration rate. Hepatic dysfunction also
enhances renal sodium retention through an undefined mechanism. Portal
hypertension then causes the excess fluid to
localize
in the peritoneal cavity (Yeung & Wong, 2002). Another factor in the development of ascites is decreased
production of albumin by hepatocytes, and the altered liver metabolism allows
an accumulation of the hormones that regulate the sodium and water balance.
This stimulates the various sodium channels and contributes to the ascites.
Hepatic
encephalopathy is complex and the pathophysiology that leads to it is not well
understood. There are several hypotheses
regarding this and the most common and most accepted is linked to ammonia,
which is what this paper will focus on. According to McCance (2006) hepatic
encephalopathy probably is the result of altered neurotransmission caused by a
combination of biochemical alterations.
Sargent (2006) states its cause is multifactorial, and can be attributed
to endogenous neurotoxins such as mercaptans (derivatives of methionine),
phenols, ammonia, and short and medium chain fatty acids, changes in
neurotransmitter and receptors, or an increase in permeability of the blood
brain barrier. When the liver fails it is unable to detoxify ammonia as it is
supposed to, leading to high levels of ammonia in the blood (Faint,
2006).
Skeletal
muscle can decrease blood ammonia by metabolizing ammonia to glutamine. Its
role is to buffer the ammonia produced in the intestines which does not get
metabolized by the liver. The kidneys determine levels of blood ammonia by
excreting urea in the urine and generating ammonia, playing an important role
in regulating blood ammonia levels. There has been an increase of generation of
ammonia by the kidneys shown after GI bleeding (Cordoba & Minguez, 2008). Once this
ammonia reaches the brain and seeps through the blood-brain barrier it can
alter cerebral energy metabolism, cause edema, or interfere with
neurotransmitters. A rise in blood ammonia may affect
brain function by inducing several disturbances
in astrocytes; these may impair mitochondria
and the glutamate-glutamine trafficking between neurons and astrocytes (Cordoba & Minguez, 2008). These disturbances are why the brain does not function as
it should and the clinical manifestations of encephalopathy are seen.
In addition to ascites and hepatic encephalopathy, splenomegaly and varices are common manifestations of liver disease. All of these manifestations are the result of portal hypertension. Portal hypertension is caused by disorders that obstruct or impede blood flow through any component of the portal venous system or vena cava. The most common cause of portal hypertension is obstruction caused by cirrhosis of the liver (Huether & McCance).
Splenomegaly, (enlargement of the spleen) is caused by increased pressure in the splenic vein, which branches from the portal vein. The spleen is a small organ located just below the rib cage on the left side. The spleen has many important functions. It filters out and destroys old and damaged blood
cells, along with storing blood and platelets (the cells that help your blood clot). It also plays a key role in preventing infection by producing lymphocytes (white blood cells), and acting as a first line of defense against invading pathogens. Treatment for the enlarged spleen focuses on relieving the underlying condition, in this case, liver disease resulting in portal hypertension.
Splenomegaly can reduce the number of healthy red blood cells, platelets, and white blood cells. This may cause anemia, increased bleeding, and increased susceptibility to infection. More serious is the risk of a ruptured spleen. Even healthy spleens are soft and easily damaged. When the spleen is enlarged, the possibility of rupture is greater. A ruptured spleen can cause life- threatening bleeding into the abdominal cavity (Mayo Clinic Staff, 2008).
Varices are distended, tortuous, collateral veins. They occur when there is long term portal hypertension. This prolonged elevation of pressure in collateral veins causes their transformation into varices. This often occurs in the lower esophagus and stomach, but can also occur in the rectum (Huether & McCance, 2008).
Vomiting of blood from bleeding esophageal varices is the most common clinical manifestation of portal hypertension (Huether & McCance, 2008). Once a bleeding episode has occurred, there is greater risk of it occurring again. In fact, up to seventy percent of people will have another bleeding episode within one year of the first (Mayo Clinic Staff, 2008). The risk of repeat bleeding is compounded if you are older, have liver or kidney failure, or drink alcohol.
Portal hypertension is often diagnosed at the time of variceal bleeding and confirmed by endoscopy and evaluation of portal venous pressure (Huether & McCance, 2008). Emergency management of bleeding varices includes the use of vasopressors and compression of the varices with an inflatable Senstaken-Blakemore tube, sclerotherapy, or variceal ligation. Surgical shunts may also be used to decompress the varices, but this can worsen encephalopathy of liver failure. Liver transplant is an alternative with end-stage liver disease (Huether & McCance, 2008). The first line of treatment for
hepatic encephalopathy is to discontinue the use of depressant drugs that are metabolized by the liver, and to correct fluid and electrolyte balances (McCance & Huether, 2006). A high blood ammonia content is one of the main causes of hepatic encephalopathy so lowering the ammonia levels is a major goal in its treatment. The colon is the focus for ammonia level control and patients are started on disaccharides such as Lactulose and lactiol (Bajaj, 2008) which is broken down to lactic acid and affects
the production and absorption of ammonia (Sargent, 2006). Antibiotics such as neomycin, rifaximin, and vancomycin are used to kill intestinal bacteria, however caution must be used because they can have severe secondary effects themselves (Cordoba & Minguez, 2008). Probiotic yogurts, synbiotics, and probiotics have all also been shown to help reverse hepatic encephalopathy, although the exact mechanism of action has not been found (Bajaj, 2008). A protein restricted diet used to be a mainstay of treatment as well, however recent research has shown that while high protein diets induce hyperammonemia, the reverse may not be true (Cordoba & Minguez, 2008). As a result of these findings, a protein restricted diet is no longer the recommendation for a patient with hepatic encephalopathy. Liver transplant has been thought to completely reverse the effects of hepatic encephalopathy however new studies are challenging that belief. According to Cordoba & Minguez (2008) hepatic encephalopathy may cause some irreversible neurological damage.
Malnutrition
in the alcoholic
Alcohol use can contribute to malnutrition in two ways. First of all, if the alcoholic is replacing nutrients with alcohol, the person will become malnourished. Secondly, even if a chronic alcoholic takes in enough nutrients, alcohol interferes with the absorption of many nutrients. It has been shown that alcoholics have deficiencies in certain vitamins, particularly thiamine, riboflavin, pyyridocine, ascorbic acid, and folic acid (Lieber, 2003 ). That is why often chronic alcoholics are given an intravenous solution containing thiamine, a multivitamin, and folic acid when they present to the hospital. As all vitamins are important to overall wellbeing, thiamine deficiency can lead to cerebral damage. Thiamine deficiency can lead to Wernicke’s encephalopathy, a neurologic disorder in which
the patient suffers from acute confusion, nystagmus, paralysis of the oculomotor nerve, ataxia and polyneropathy. Often the patient doesn’t know he has these symptoms, or they are taken for symptoms of a head injury (Dawood, 2008).
Nutrition therapy in the chronic alcoholic is aimed at correcting electrolyte disturbances and shedding access fluid. Protein is essential as it can help to regenerate functional liver tissue. Sodium
should be restricted to help reduce fluid retention. Foods should be soft, to avoid perforating an esophageal varice. Vitamins should be given to the patient in amounts almost twice that of what a healthy person should need. Lastly, and obviously, alcohol should be taken completely from the diet (Williams, 1999). Alcoholism at many points in time was thought to be a personality flaw or moral weakness. We now know that alcoholism is at least partly genetic. The specifics of which genes are involved and how they interact in the body has yet to be determined (McClearn et al., 1998). While many people can abuse alcohol, only a certain people’s biochemistry makes them very susceptible to alcoholism while others’ biochemistry makes them much less so. The addictive pull can be strong or weak, depending on the person’s genetic makeup.
There are also certain personality factors that can contribute to alcoholism. A quick temper, certain metabolic patterns, a willingness to take risks and high level of anxiety are a few of the known personality traits. If a person lives in a culture where alcohol is not available, even if they have a strong genetic affinity to become an alcoholic, the genetic factors will not manifest. If, however, a person is raised in an environment where alcohol is available, this person may become an active alcoholic. It depends also on the individual’s choices, personality and social influences.
As a young child, we may be born with the “genetic” factor to be an alcoholic but we display our parent’s interests and behaviors. As we mature and become independent, we begin to seek out our own environments that reinforce our biological, rather than familial, traits that we begin to see our genetic traits reinforced (Scarr, 1994). This has been seen in many studies with adoptive children when as children they reflect their adoptive parent’s interest and influences. When they begin to become
dependent, their genetic parents
influence is reinforced along with their individual personality and decisions.
A close example would be of Oskar Stohr and Jack Yufe who are identical twins
born of a Jewish father and Christian mother in
enjoyed the same spicy foods and sweet liquors, are absent-minded, have a habit of falling asleep while watching TV, think it’s funny to sneeze in front of a crowd of strangers, flush the toilet before using it, store rubber bands on their wrists, read magazines from back to front, dip buttered toast in their coffee and are domineering towards their wives. Their scores on psychological tests were very similar and personalities are remarkably similar.
According to Berger (2007), heritability refers to the variation in a particular trait, in a particular population, in a particular environment, and it expresses the degree to which that variation can be attributed to genetic differences among the members of the group. Whenever you encounter heritability estimates, they can never be applied to individual cases or used to assess trait differences between groups. Let us say that intelligence is between 50-75 percent heritability means that within a particular group, between 50-75 percent of an individual’s intelligence (as measured by IQ tests) is due to genes. In other words, it does not mean that 50-75 percent of an individual’s intelligence is inherited and the rest is due to environment. Within-group heritability may be fairly high, than between group differences. An average IQ may be attributable to environmental differences like socioeconomic, opportunities to learn and support that each group’s culture provide which the IQ measures.
It is quite clear that there is a complex influence that occurs between both genes and the environment on every aspect of development whether it’s a good sense of humor or a risk of becoming addicted to alcohol. Genes are a part of the determining outcome but they don’t determine the final story (Scarr, 1999).
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