Kamis, 26 April 2012

english scenario blok 11


Scenario:
Profile:
55 years old woman
Loss of memory and weakness
History illness:
4 years ago à total gastrectomy for adenocarcinoma of the stomach
Px Examination:
BP: 110/70 mmHg
Pulse: 96/ minutes
Palpation of her abdomen: no masses, liver and spleen were not palpable
Lab Examination:
Hb: 9 gr/dL
MCV: 110 fl
WBC: 3400/ microliter
Neutrophils hypersegmentation, macrocytosis, poikilocytosis, anisocytosis

Hai memed, this is our scenario for the english tutorial tomorrow. Let’s see what mimin can share for memed. First, maybe there are some terms which are still unfamiliar, such as:

  • Gastrectomy: Surgical excision of all or more commonly part of the stomach. It is performed to remove a chronic peptic ulcer, to stop hemorrhage in a perforating ulcer, or to remove malignancy.
  • Adenocarcinoma: Any one of a large group of malignant, epithelial cell tumors of the glands.

Next step, the problems based on the scenario:

  1. 1.      What are the causes of loss of memory and weakness?
  2. 2.    Is there any relation between the condition of that woman (loss of memory and weakness) with her history illness?
  3. 3.     What is the interpretation of the lab examination? And it’s relation with her condition
  4. 4.      How about the longrange effect of  total gastrectomy for adenocarcinoma of the stomach?

Form those questions, we can analyze them on this step

Reversible causes of memory loss

It’s important to be aware of ways that your health, environment, and lifestyle may contribute to memory loss. Sometimes, even what looks like significant memory loss can be caused by treatable conditions and reversible external factors.
·      Side effects of medication. Many prescribed and over-the-counter drugs or combinations of drugs can cause cognitive problems and memory loss as a side effect. This is especially common in older adults because they break down and absorb medication more slowly. Common medications that affect memory and brain function include sleeping pills, antihistamines, blood pressure and arthritis medication, antidepressants, anti-anxiety meds, and painkillers.
·    Depression. Depression can mimic the signs of memory loss, making it hard for you to concentrate, stay organized, remember things, and get stuff done. Depression is a common problem in older adults—especially if you’re less social and active than you used to be or you’ve recently experienced a number of important losses or major life changes (retirement, a serious medical diagnosis, the loss of a loved one, moving out of your home).
·   Vitamin B12 deficiency. Vitamin B12 protects neurons and is vital to healthy brain functioning. In fact, a lack of B12 can cause permanent damage to the brain. Older people have a slower nutritional absorption rate, which can make it difficult for you to get the B12 your mind and body need. If you smoke or drink, you may be at particular risk. If you address a vitamin B12 deficiency early, you can reverse the associated memory problems. Treatment is available in the form of a monthly injection.
·     Thyroid problems. The thyroid gland controls metabolism: if your metabolism is too fast, you may feel confused, and if it’s too slow, you can feel sluggish and depressed. Thyroid problems can cause memory problems such as forgetfulness and difficulty concentrating. Medication can reverse the symptoms.
·     Alcohol abuse. Excessive alcohol intake is toxic to brain cells, and alcohol abuse leads to memory loss. Over time, alcohol abuse may also increase the risk of dementia. Because of the damaging effects of excessive drinking, experts advise limiting your daily intake to just 1-2 drinks.
·      Dehydration. Older adults are particularly susceptible to dehydration. Severe dehydration can cause confusion, drowsiness, memory loss, and other symptoms that look like dementia. It’s important to stay hydrated (aim for 6-8 drinks per day). Be particularly vigilant if you take diuretics or laxatives or suffer from diabetes, high blood sugar, or diarrhea.

Total gastrectomy for adenocarcinoma of the stomach
The most common metabolic defect appearing following gastrectomy is anemia. Two type have been identified: one is related to a deficiency in iron and the other is related to an impairment in vitamin B12 metabolism.
Megaloblastic anemia can also occur following gastrectomy, especially when more then 50% of the stomach is removed. Because gastric juice produce some instrinsic factor secrete  which has a relation with the produce of vitamin B12. Vitamin B12 is one of factor in folic acid metabolism, so when patien get vitamin B12 deficiency, she will get lack of folic acid. Vitamin B12 and folic acid are subtances that in charge in eritopoiesis.
Factors associated with increassed risk of developing stomach cancer
Nutritional:
Low fat or protein consumption
Salted meat or fish
High nitrate consumption
High complex-carbohydrate consumption
Environmental:
Poor food preparation (smoked, salted)
Lack of refrigeration
Poor dringking water (well water)
Smoking
Medical:
Prior gastric surgery
H. Pylori infection
Gastric atrophy and gastritis
Adenomatous polyps
Male gender

Neutrophil
The mature neutrophil is easily recognize by its unique morphology. Hypersegmented Neutrophils are larger than normal neutrophils with five or more segmented nuclear lobes. They are commonly seen with folic acid or vitamin B12 deficiency. 

A hypersegmented neutrophil is a clinical laboratory finding. It is visualized by drawing blood from a patient and viewing the blood smeared on a slide under a microscope. Normally, the number of segments in the nucleus of a neutrophil increases as it matures and ages, after being released into the blood from the bone marrow. Whereas normal neutrophils only contain three or four  lobes (the "segments"), hypersegmented neutrophils contain six or more lobes.
Hypersegmented neutrophils have classically been thought to be pathognomonic of the class of anemias called megaloblastic anemia (anemias caused by failure of bone marrow blood-forming cells to make DNA, often caused by vitamin B12 or folate deficiencies, or DNA-replication poisons). However, in seeming contradiction to this, several studies have strongly associated neutrophil hypersegmentation with iron deficiency anemia.[2] In one study 81% of children with iron deficiency had hypersegmented neutrophils, vs. 9% of controls.[3] The mechanism for hypersegmentation in iron deficiency is not yet clear, but has been suggested to be concurrent iron and vitamin deficiency.
One of the earliest, notable changes in the peripheral blood in megaloblastic processes is the appearance of hypersegmented neutrophils. Because of the short life-span of neutrophils, these abnormal hypersegmented neutrophils characteristically appear even before the onset ofanemia in megaloblastic processes.Such neutrophils are less often seen in the other classes of anemia, which together are far more common than megaloblastic types of anemia. However, as noted, the use of hypersegmented neutrophils to diagnose type of anemia is limited by the fact that different types of nutrient deficiency anemia may coexist.

Anemia

You get anaemia when you don't have enough red blood cells. This makes it difficult for your blood to carry oxygen, causing unusual tiredness and other symptoms.
The number of red blood cells can drop if there :
1.      a reduction in the number of red blood cells produced
2.      an increase in the loss of red blood cells.

Red blood cells and oxygen

Through its pumping action, the heart propels blood around the body through the arteries.
The red blood cells take up oxygen in the lungs and carry it to all the body's cells. Your cells use this oxygen to fuel the combustion (burning) of sugar and fat which produces the body's energy.
During this process carbon dioxide is created as a waste product. It binds itself to the red blood cells that have delivered the oxygen.
The red blood cells then transport the carbon dioxide back to the lungs. We exchange this carbon dioxide for fresh oxygen by breathing.
This process is called oxidation.

Why does vitamin B12 deficiency cause anaemia?

Red blood cells are made in the bone marrow and circulate in the blood. They only have a life expectancy of about four months.
The body needs iron, vitamin B12 and folic acid(one of the B group of vitamins) to produce more red blood cells. If there is a lack of one or more of these nutrients, anaemia will develop.
Anaemia due to a lack of vitamin B12 is also called pernicious anaemia.
Vitamin B12 is essential for the nervous system, which is why a deficiency can also cause inflammation of the nerves (neuritis) and dementia (mental deterioration).
eldery poeple are particularly at risk of vitamin B12 deficiency, although it may also be present in the young women.

What causes this type of anaemia?

·      Not eating enough foods that contain vitamin B12. A vegetarian or vegan diet can cause deficiency because vitamin B12 is only found in foods of animal origin, such as meat, fish, eggs and milk.
·      Inability of the small intestine to absorb vitamin B12. The stomach produces a substance called intrinsic factor to absorb vitamin B12 from food. In the UK, the most common cause of B12 deficiency is a lack of intrinsic factor.

What causes a low production of intrinsic factor?

·      Antibodies can form against the cells that produce intrinsic factor. The cells then die, leading to B12 deficiency and anaemia.
·      Stomach canncer and ulcers can take up so much room in the stomach that there are too few cells left to produce intrinsic factor.
·      Diseases of the small intestine, fish tapeworm and the after-effects of bowel surgery can all result in the surface of the small intestine being too small to absorb B12 and intrinsic factor effectively.

What are the symptoms of this type of anaemia?

If a person is otherwise healthy, it can take some time for the signs of anaemia to appear.
·     The first symptoms will be tiredness and palpitations (awareness of heartbeat).
·     Shortness of breath and dizziness (fainting) are also common.
·      If the anaemia is severe, it can result in angina (chest pain), headache and leg pains (intermittent claudication).
·      Red, sore tongue and mouth.
·      Weight loss.

How is pernicious anaemia diagnosed?

A bloos sample is taken and sent off to the laboratory. An analysis of the red blood cells is usually included with the result of the test.
In cases of vitamin B12 deficiency, the red blood cells will be the usual colour but larger than normal.
If the blood test shows a low vitamin B12 count, it must be established whether it is pernicious anaemia or if there is some other cause.
The Schilling test measures the body's ability to absorb vitamin B12 from the bowel. This will show whether the anaemia is caused by a lack of intrinsic factor.
Blood tests will also confirm if you have any antibodies to intrinsic factor.
People with a history of diabetes, thyroid upset or vitiligo (depigmentation of the skin), whether in themselves or in there family, are at higher risk of developing intrinsic factor antibodies and pernicious anaemia.

What can be done to avoid vitamin B12 deficiency?

·     Eat a varied diet. Good sources of vitamin B12 are liver, fish and eggs.
·     Vegans should take vitamin B12 supplements to avoid deficiency.
·     If a family member has pernicious anaemia, you should take extra care to prevent deficiency.
·     Anyone who has undergone surgery in their small intestine or stomach should pay attention to any of the symptoms mentioned above.

 

Megaloblastic anemias are a heterogeneous group of disorders that share common morphologic characteristics. The morphological hallmark of megaloblastosis is a megaloblast. Megaloblasts are large cells with an increased nuclear/cytoplasmic ratio in which nuclear maturation is delayed, while cytoplasmic maturation is more advanced. Peripheral smears reveal that RBCs are macrocytic and occasional megaloblasts are present. Megaloblasts are usually abundant in bone marrow aspirates. Megaloblastic changes are not limited to RBCs since hypersegmented neutrophils can be seen on peripheral smears, and pancytopenia occurs in megaloblastic anemias.
Megaloblastosis is a generalized disorder involving most rapidly growing cells, such as gastrointestinal and uterine cervical mucosal cells. The etiology of megaloblastosis is diverse, but a common basis is impaired DNA synthesis. The most common causes of megaloblastosis are cobalamin (vitamin B-12) and folate deficiency.
Serious organ failure can occur in individuals with megaloblastosis. Both vitamin B-12 and folate deficiencies can cause memory loss, depression, personality changes, and psychosis, as well as peripheral neuropathy. Vitamin B-12 deficiency can cause subacute combined dorsal and lateral spinal column degeneration, in which patients develop ataxia, become weak, and lose proprioceptive and vibratory senses. If not treated, mental and neurological changes can become permanent.
The requirement for folic acid increases during pregnancy due to increased metabolism and cell turnover. Serious neural tube defects and other developmental abnormalities can occur in the fetus if additional folate has not been provided prenatally.

Pathophysiology

The common feature in megaloblastosis is a defect in DNA synthesis in rapidly dividing cells. To a lesser extent, RNA and protein synthesis are impaired. Unbalanced cell growth and impaired cell division occur since nuclear maturation is arrested. More mature RBC precursors are destroyed in the bone marrow prior to entering the blood stream (intramedullary hemolysis).
The most common causes for megaloblastosis are cobalamin (Cbl) and folate deficiencies, medications, and direct interference of DNA synthesis by HIV infections and myelodysplastic disorders.

Cobalamin

The primary sources of vitamin B-12 (a cobalt-containing vitamin) are meat, fish, and dairy products. Cyano - Clb is not a natural form but is an in vitro artifact. 5’-Deoxyladenosyl-Clb, methyl-Clb, and hydroxo-Clb are active forms and occur naturally.
Complex interactions between cobalamins (5’-deoxyladenosyl-Clb, methyl-Clb) and folates (pterolylpolyglutamates [PteGlus]) are important for the synthesis of methionine and thymidine and, hence, DNA synthesis. Perturbation in the availability and the metabolism of cobalamin and folate are the primary causes for the impairment of DNA synthesis in megaloblastosis. An in-depth review of this subject is beyond the scope of this article but is detailed in several references.The mechanisms for patchy demyelination and other neurological consequences of cobalamin deficiency appear to be independent and different from those responsible for the development of a megaloblastic anemia.
The uptake of cobalamin is complex. Dietary cobalamin binds nonspecifically to proteins, and gastric digestion at a low pH releases cobalamin from these proteins. Released cobalamin then binds to R-proteins. As the cobalamin-R-protein complexes enter the duodenum, R-proteins are degraded by pancreatic enzymes and cobalamin is released. Cobalamin released from R-proteins is free to bind to intrinsic factor (IF). IF is produced in the gastric fundus and cardia. The role of IF is to stabilize cobalamin and transport it to the terminal ileum. Cobalamin-intrinsic factor complexes are processed by receptors in the terminal ileum, and cobalamin is released and absorbed.
The absorbed cobalamin is bound to transcobalamin II (TC II). TC II transports cobalamin to cells that internalize and use cobalamin for DNA synthesis. Transcobalamin I (TC I) might be involved in cobalamin storage and is elevated in leukocytes in patients with chronic myelogenous leukemia. Cobalamin is the only water-soluble vitamin stored in the body. About 3 mg of cobalamin are stored, of which 1 mg is stored in the liver.
The sources of folates or PteGlus are ubiquitous, and folates are found in vegetables, fruits, and animal protein. Both monoglutamate and polyglutamate forms exist in nature.

Uptake of folates

Physiological folate absorption and transport is receptor mediated. There is no equivalent of intrinsic factor to stabilize and transport ingested folate. Uptake occurs in the jejunum and throughout the small intestine.

Etiology

Major causes for cobalamin deficiency

The daily requirement cobalamin is about 5-7 µg/d. As mentioned, large amounts of cobalamin are stored in liver and other sites. Therefore, cobalamin deficiency only develops about 3-4 years after the cessation of cobalamin uptake.
Dietary cobalamin deficiency rarely causes megaloblastic anemia, except in strict vegetarians who avoid meat, eggs, and dairy products. Atrophic gastritis and achlorhydria commonly occur in elderly persons.These conditions are responsible for the impaired release of protein-bound cobalamins and, hence, can interfere with cobalamin uptake. This is a common problem in elderly persons.
There is a failure in intrinsic factor (IF) secretion in pernicious anemia, owing to autoimmune destruction of gastric parietal cells. Pernicious anemia is the best-known cause for cobalamin deficiency. Cobalamin is not absorbed in the absence of IF. Pernicious anemia is diagnosed in about 1% of people older than 60 years, and the incidence is slightly higher in women than in men. It should be noted that H2 antagonists can inhibit IF secretion.
In pancreatic insufficiency, pancreatic enzymes are not available to facilitate the release of cobalamins from R-proteins and thus cobalamins are not absorbed. In Zollinger-Ellison syndrome, the secretion of large amounts of acid inactivates pancreatic enzymes.
Disorders of the terminal ileum can result in cobalamin deficiency. Because the terminal ileum is the site of uptake of cobalamin-IF complexes, tropical sprue, inflammatory bowel disease, lymphoma, and ileal resection can lead to cobalamin deficiency. Tropical sprue is more severe than nontropical sprue (celiac disease) and can be associated with both cobalamin and folate deficiencies. It takes several years for cobalamin deficiency to develop after the onset of these disorders because of the time required to deplete cobalamin reserves.
Blind loop syndrome can result in cobalamin deficiency. Bacterial colonization can occur in intestines deformed from strictures, surgical blind loops, scleroderma, inflammatory bowel disease, or amyloidosis. Bacteria then compete with the host for cobalamin.
The fish tapeworm Diphyllobothrium latum can compete with the host for ingested cobalamin. This organism is most often found in Canada, Alaska, and the Baltic Sea.
Nitrous oxide exposure can cause megaloblastosis by oxidative inactivation of cobalamin. Prolonged exposure to nitrous oxide can lead to severe mental and neurological disorders.
The details of hereditary disorders are beyond the scope of this review, but information can be found in other references.
A partial list of medications that can cause cobalamin deficiency includes purine analogs (6-mercaptopurine, 6-thioguanine, acyclovir), pyrimidine analogues (5-fluorouracil, 5-azacytidine, zidovudine), ribonucleotide reductase inhibitors (hydroxyurea, cytarabine arabinoside), and drugs that affect cobalamin metabolism (p -aminosalicylic acid, phenformin, metformin).

Major causes for folate deficiency

The daily requirement for adults is about 0.4 mg/d. Storage is limited, and folate deficiency develops about 3-4 weeks after the cessation of folate intake.
Dietary folate deficiency is a cause. In the United States, most people obtain sufficient folate from fortified foods. However, alternate diets may contain little folate. The preparation of foods is a major cause for folate deficiency, especially in elderly persons. Folates are very thermolabile. Therefore, excessive heating can lead to inactivation, especially when foods are diluted in water.
Failure to increased folate supplementation in response to increased demand can result in deficiency. There is an increased need for folate in the face of hemolysis, pregnancy, lactation, rapid growth, hyperalimentation, renal dialysis, psoriasis, and exfoliative dermatitis.
Intestinal disorders that impede folate absorption include tropical sprue, nontropical sprue (celiac disease or gluten sensitivity), amyloidosis, and inflammatory bowel disease.
With alcoholism, the bioavailability of folate and folate-dependent biochemical reactions can be impaired.
A partial list of medications that can cause folate deficiency includes phenytoin, metformin, phenobarbital, dihydrofolate reductase inhibitors (trimethoprim, pyrimethamine), methotrexate and other antifolates, sulfonamides (competitive inhibitors of 4-aminobenzoic acid), and valproic acid.
The details of hereditary disorders that cause folate deficiency are beyond the scope of this review, but information can be found in other references).

Other causes for megaloblastosis

Megaloblastosis in HIV infection and myelodysplastic disorders is due to a direct effect on DNA synthesis in hematopoietic and other cells.


Author: Zulva
Reference:

  1.   Hillman, Robert S. 2005. Hematology in Clinical Practice.America:Mc Graw Hill
  2. Townsend, Courtney M.2004. Textbook of Surgery.USA: Elsevier
  3. http://www.netdoctor.co.uk/diseases/facts/anaemiab12.htm
  4. http://www.helpguide.org/life/prevent_memory_loss.htm
  5. http://emedicine.medscape.com/article/204066-overview#a0156

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