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. What are the causes of loss of memory and weakness?
- 2. Is there any relation between the condition of that woman (loss of memory and weakness) with her history illness?
- 3. What is the interpretation of the lab examination? And it’s relation with her condition
- 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:
- Hillman, Robert S. 2005. Hematology in Clinical Practice.America:Mc Graw Hill
- Townsend, Courtney M.2004. Textbook of Surgery.USA: Elsevier
- http://www.netdoctor.co.uk/diseases/facts/anaemiab12.htm
- http://www.helpguide.org/life/prevent_memory_loss.htm
- http://emedicine.medscape.com/article/204066-overview#a0156
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