Thyroid is one of the largest
endocrine glands found in the neck, below the Adam's Apple with the
function of regulating the body use of energy, make of proteins by
producing its hormones as a result of the stimulation of
thyroid-stimulating hormone (TSH) produced by the anterior pituitary.
Thyroid disease is defined as a condition of malfunction of thyroid.
Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones.
Hypothyroidism is a condition in which the thyroid gland is under active and produces very little thyroid hormones
. Thyroid cancer is defined as condition in which the cells in the thyroid gland have become cancerous.
Thyroid hormone resistance syndrome
Thyroid hormone resistance syndrome is defined as a condition of which affected individuals have elevated serum thyroid hormone levels and
inappropriately normal or elevated thyroid-stimulating hormone (TSH) but
are usually clinically euthyroid and require no treatment. Selective
pituitary resistance to thyroid hormone (PRTH) is characterized by
resistance in the pituitary gland but not in peripheral tissues(a).
A. Symptoms
1. hyperactivity, emotional lability, a below average intelligence quotient, and short stature
Thyroid hormone resistance
mutations are associated with a wide variety of phenotypes and
subsequent treatment challenges. Among the more common symptoms are
hyperactivity, emotional lability, a below average intelligence
quotient, and short stature(1).
2. Hyperthyroid symptoms
There is a first
case report of a
resistance to
thyroid hormone
in a neonate presenting with hyperthyroid symptoms born to a mother
with Graves' disease and treated with methimazole and iodine(2). such as Sudden weight loss, rapid heartbeat (tachycardia), increased appetite, nervousness, anxiety and irritability, tremor, etc(3).
3. Psychiatric disorders
There is a report of six children from five unrelated families with
esistance to
thyroid hormone (RTH). All patients grew normally and presented variable symptoms that were
treated according to need. Two patients developed psychiatric disorders.
Only one of the four affected parents exhibited clinical signs of RTH
(tachycardia and depression)(4).
4. Other symptoms
According to the study by the Northwestern University Medical School,, clinical effects of RTH can include short stature, delayed bone
maturation, hyperactivity, learning disabilities, and hearing defects,
as well as variable features of hyper- and hypothyroidism(5). Others indicated that RTH symptoms include failure to thrive, growth retardation and attention-deficit
hyperactivity disorder in childhood, and goitre and thyrotoxic cardiac
symptoms in adults(5a).
B. Causes
Genetic mutation
Thyroid hormone resistance occurs when a genetic mutation in the
thyroid hormone receptor leads to reduced
hormone binding affinity; the concentration of free
thyroid hormone in the circulation is inversely correlated with the
hormone binding affinity of the mutant receptor(6),
such as mutation in the THRbeta gene, A317T(7) and E333D(8). According to the study of Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination by the University of Chicago, Mutations in MCT8 and SECISBP2 have also been associated with this condition(9) and a patient with the unusual coincidence of two rare
congenital disorders, lingual ectopy of the
thyroid gland and
resistance to
thyroid hormone (RTH), resulting in impaired
thyroid hormone production and action, respectively(10). Thyroid hormone resistance syndrome affect approximately 1 in 40,000
live births and of of which over 100 different mutations have been
identified.
B.2. Risk factors
1. Dominant inheritance
Resistance to
thyroid hormone (RTH) is an inherited
syndrome of reduced tissue responsiveness to
thyroid hormone. To date, all individuals expressing the RTH phenotype have been found to harbor mutations in the
thyroid hormone receptor beta (TR beta) gene that impair T3-mediated function(11). Others reported a baby at age 70 days, an R243W mutation in
thyroid hormone
receptor β was detected in our patient; while absent in his mother, the
mutation was present in his father, who never showed any symptoms(12).
2. Graves' disease
Resistance to
thyroid hormone is a
syndrome caused by
thyroid hormone receptor β mutations, which are usually inherited in an autosomal-dominant pattern. There is a report of a
resistance to
thyroid hormone
in a neonate presenting with hyperthyroid symptoms born to a mother
with Graves' disease and treated with methimazole and iodine(12).
3. Minor alterations at the
DNA level
Mutations in the
thyroid hormone
receptor (TR) beta gene are responsible for RTH and 122 different
mutations have now been identified belonging to 300 families. With the
exception of one family found to have complete deletion of the TRbeta
gene, all others have been demonstrated to have minor alterations at the
DNA level, according to the study by the Stoke Mandeville Hospital(13).
C. Complications and diseases associated to Thyroid hormone resistance
C.1. Complications
1. Growth retardation/short stature and skeletal dysplasia
There is a report of a first human cases (female, age 6 y; father and daughter, ages 47 and 11
y, respectively) with growth retardation/short stature, skeletal
dysplasia, constipation, and defective
thyroid receptor α (TRα)(14).
2. Thyroxine excess and inappropriate TSH secretion
Resistance to
thyroid hormone (RTH) is an uncommon inherited cause of hyperthyroxinemia with inappropriate TSH secretion, according to the study by the University of Cambridge, Addenbrooke's Hospital, United Kingdom(15).
3. Cardiovascular risk
RTH patients show evidence in this study of increased augmentation index
consistent with an increase in arterial stiffness compared with
euthyroid controls. They also demonstrate elevated LDL-cholesterol
levels. Both these measures may lead to increased cardiovascular risk(16).
C.2. Diseases associated to Thyroid hormone resistance
1. Differentiated thyroid cancer (DTC)
There are reports of four unusual cases of DTC associated with TSHoma (2 cases), RTH (1
case), and an elevated TSH of unknown etiology (1
case)(17).
2. A pituitary tumor
There is a report of a woman in whom the standard evaluation for inappropriate TSH secretion
was insufficient to distinguish these entities. The patient had a
low-normal TRH stimulation test and an unmeasurable alpha-glycoprotein
subunit level; however, a pituitary magnetic resonance imaging (MRI)
revealed an adenoma. More testing using a T3 suppression test supported a
RTH diagnosis and a R438H mutation was found in the TR-beta gene. To
our knowledge, this represents the first report of an apparently
incidental pituitary adenoma in the setting of documented
resistance to
thyroid hormone. As such, it raises the question of whether RTH predisposes to pituitary hyperplasia and adenoma. development(18).
3. Papillary thyroid carcinoma
There is an association of
thyroid hormone resistance syndrome and papillary
thyroid carcinoma(19).
4. Immune thrombocytopenic purpura (ITP)
There is a report of a 9-year-old girl presented with ITP and features of hypothyroidism in the
form of goiter and growth retardation. She was subsequently found to
have RTH. High-dose
thyroid hormone replacement was required to overcome the
resistance that not only ameliorated the features of hypothyroidism but also brought an apparent remission of ITP(20).
5. Postpartum thyroiditis
there is a repopt of a report of a unique
case
of a woman affected by RTH, due to a novel mutation V283A in THRB, who
experienced PPT with a severe thyrotoxic phase after both her
pregnancies. The association between RTH and PPT has never been reported
in the literature. In particular, the marked suppression of TSH
occurring when levels of TH are particularly elevated is not a frequent
condition during RTH(21).
6. Chronic thyroiditis
There is a report of the five-year medical history of a Japanese woman and her father with RTH and coincidental chronic thyroiditis(22).
D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
1. Hyperthyroidism
There is a report of an isolated
case
of RTH initially misdiagnosed as hyperthyroidism, and detail the
investigations which ultimately led to the correct diagnosis(23).
2. Falsely diagnnosis
There is a report of a 63-year-old woman was referred because of suspected SITSH. Laboratory
tests showed a normal TSH (0.52 μIU/L; normal range: 0.5-5.0) measured
by sandwich Elecsys, and elevated FT4 (3.8 ng/dL; normal range: 0.9-1.6)
and FT3 (7.6 pg/mL; normal range: 2.3-4.0), determined by competitive
Elecsys. To exclude possible assay interference, aliquots of the
original samples were retested using a different method (ADVIA Centaur),
which showed normal FT4 and FT3 levels. Eight
hormone levels, other than
thyroid
function tests measured by competitive or sandwich Elecsys, were higher
or lower than levels determined by an alternative analysis. Subsequent
examinations, including gel filtration chromatography, suggested
interference by substances against ruthenium, which reduced the
excitation of ruthenium, and resulted in erroneous results(24). Other suggested that patients with TSH-secreting pituitary tumors(TSHoma) also manifest SITSH.
Thus, the differential diagnosis of RTH vs. TSHoma is sometimes
difficult and challenging. In this review article, the etiology of RTH
and
diagnostic approach for SITSH are explained and an algorithm for differential diagnosis of RTH vs. TSHoma is proposed(25).
3. Coexistence of mutation genes
There is a report of the coexistence of THRB and TBG gene mutations in the same
individual (mother of the proband), whereas other affected family
members had only 1 of the 2 genes mutated. The
case illustrates the difficulty that might be encountered in the interpretation of
thyroid function tests when different genetic defects affecting
thyroid function coexist(26).
4. Grave's disease
RTH is often misdiagnosed as Graves' disease. However, these disorders
can coexist, and the concurrent presence of both disorders in a patient
can present diagnostic challenges. A previous report of a patient with
Graves' disease associated with RTH was published before gene sequencing
could be used to confirm diagnosis of RTH. There is a report of a patient with
Graves' disease and concurrent RTH that was confirmed by gene
sequencing, showing a mutation in the
thyroid hormone receptor beta gene(27).
D.2. Diagnosis
If you are experience certain symptoms of the above and your doctor suspects that you have developed acute thyroiditis, after
recording the past and present history and completing a physical
exam, the
tests which your doctor orders
may include
1. Urinary test
Urinary cortisol metabolites are altered both quantitatively and qualitatively in
thyroid
dysfunction. According to the study by the Showa University, the ratio of the urinary concentrations of cortisol metabolites, THE/THF, appears to be a good marker for peripheral
thyroid hormone resistance(28).
2. Blood test
Unfortunately, the blood test results of the disorder can also be found in other disorders such as TSH-oma (pituitary adenoma), or other pituitary disorders. According to the study by the Nagoya University, almost all patients with RTH manifest unsuppressed thyrotropin (TSH)
despite elevated free-T4 and free-T3 levels. This abnormal finding in
the
thyroid function test is termed "
syndrome
of inappropriate secretion of TSH" (SITSH) or "central
hyperthyroidism". Patients with TSH-secreting pituitary tumors(TSHoma)
also manifest SITSH. Thus, the differential diagnosis of RTH vs. TSH-oma
is sometimes difficult and challenging(29)
3. Identifying a mutation of the thyroid receptor
Resistance to
thyroid hormone (RTH) is a rare condition usually diagnosed in patients with classic
thyroid function tests (TFTs) of elevated
thyroid hormone levels with nonsuppressed TSH. According to the study by the, At least six major steps are required for secreted thyroid hormone (TH)
to exert its action on target tissues. Mutations interfering with three
of these steps have been so far identified. The first recognized defect,
which causes resistance to TH, involves the TH receptor β gene and has
been given the acronym RTH(30).
E. Treatments
E.1. In conventional medicine perspective
1. The table
Table. Suggested therapeutic approaches for resistance to thyroid hormone (RTH) patients.
| ___________________________________________________________________ |
| Drugs | Untoward effects and limitations |
| ___________________________________________________________________ |
| TRIAC | Effective in almost all patients |
| D-T4 | Effective in almost all patients |
| T3 | Production of daily peaks of very high T3 concentrations, which |
| contribute to maintain clinical hyperthyroidism |
Bromocriptine | Transient effect owing to TSH escape from inhibition |
| Sms analog | Transient effect owing to TSH escape from inhibition |
| Corticosteroid | Cause of severe inhibition of hypothalamic-pituitary-adrenal
axis function and cushingoid features |
| Antithyroid drugs | Cause of further increase in TSH circulating level with consequent
increase of goiter size and to hyperplasia at pituitary thyrotroph level |
| b-blockers | Effects limited to b-adrenergic blockade.
Propranolol inhibits peripheral conversion of T4 to T3, causing a
worsening of tissue hypometabolic state. Cardiac selective compounds,
such as atenolol devoid of effect on peripheral T4 conversion, appear to
be more useful(31). |
2. Limitation
According to the study by the Fitzsimons Army Medical Center, the
thyroid hormone resistance syndromes are disorders in which the body's tissues are resistant to the effects of
thyroid hormone. Generalized
resistance to
thyroid hormone (GRTH) is characterized by
resistance in the pituitary gland and in most or all of the peripheral tissues. Affected individuals have elevated serum
thyroid hormone levels and inappropriately normal or elevated
thyroid-stimulating
hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary
resistance to
thyroid hormone (PRTH) is characterized by
resistance in the pituitary gland but not in peripheral tissues. Patients have elevated serum
thyroid hormone
levels and normal or elevated TSH levels and are clinically thyrotoxic.
Therapy is usually necessary, but current choices are not completely
satisfactory. Selective peripheral
resistance to
thyroid hormone (PerRTH) is characterized by
resistance in peripheral tissues but not in the pituitary. The only patient thus far described had normal serum
thyroid hormone and TSH levels but was clinically hypothyroid and improved with
thyroid hormone
administration. All of these disorders are probably more common than is
generally recognized and are often misdiagnosed and inappropriately
treated. GRTH, in most cases studied, results from a mutation in the
thyroid hormone receptor beta gene causing an amino acid substitution in or a partial or complete deletion of the
thyroid hormone-binding domain of the receptor. The causes of PRTH and PerRTH remain to be determined(32). Other studies indicated that in this age of rapidly advancing knowledge, it is reasonable to expect
that the not too distant future will bring specific treatments for RTH.
This will probably not be in the form of gene therapy as the dominant
expression would require excision of the defective gene. The most
simple genetic approach, one within the realm of current technology, is
the selection of an oocyte from the affected mother that does not
harbor the abnormal allele for
in vitro fertilization
followed by implantation into the donor. This insures a fetus without
RTH but does not guarantee a normal pregnancy and fetal development.
The development of TH agonists and antagonists that are TR-isoform
specific would allow the stimulation or blockade of specific tissue
effects that are perturbed in a given individual with RTH(33).
Sources
(a)
http://www.ncbi.nlm.nih.gov/pubmed/8475937
(1)
http://www.ncbi.nlm.nih.gov/pubmed/18622209
(2) http://www.ncbi.nlm.nih.gov/pubmed/22905724
(3) http://www.ncbi.nlm.nih.gov/pubmed/20151830
(4) http://www.ncbi.nlm.nih.gov/pubmed/21870171
(5) http://www.ncbi.nlm.nih.gov/pubmed/8594618
(5a) http://www.ncbi.nlm.nih.gov/pubmed/9350446
(6) http://www.ncbi.nlm.nih.gov/pubmed/18622209
(7) http://www.ncbi.nlm.nih.gov/pubmed/19227423
(8) http://www.ncbi.nlm.nih.gov/pubmed/17177139
(9) h
ttp://www.bprcem.com/article/S1521-690X%2807%2900026-7/abstract
(10)
http://www.ncbi.nlm.nih.gov/pubmed/16053391
(11)
http://www.ncbi.nlm.nih.gov/pubmed/8954015
(12)
http://www.ncbi.nlm.nih.gov/pubmed/22905724
(13)
http://www.ncbi.nlm.nih.gov/pubmed/17132274
(14)
http://www.ncbi.nlm.nih.gov/pubmed/23940126
(15)
http://www.ncbi.nlm.nih.gov/pubmed/7998483
(16)
http://www.ncbi.nlm.nih.gov/pubmed/18803680
(17)
http://www.ncbi.nlm.nih.gov/pubmed/23553855
(18)
http://www.ncbi.nlm.nih.gov/pubmed/11327621
(19)
http://www.ncbi.nlm.nih.gov/pubmed/23457315
(20)
http://www.ncbi.nlm.nih.gov/pubmed/23382302
(21)
http://www.ncbi.nlm.nih.gov/pubmed/23134553
(22)
http://www.ncbi.nlm.nih.gov/pubmed/16723809
(23)
http://www.ncbi.nlm.nih.gov/pubmed/16445164
(24)
http://www.ncbi.nlm.nih.gov/pubmed/22673200
(25)
http://www.ncbi.nlm.nih.gov/pubmed/23214067
(26)
http://www.ncbi.nlm.nih.gov/pubmed/23633200
(27)
http://www.ncbi.nlm.nih.gov/pubmed/20151830
(28)
http://www.ncbi.nlm.nih.gov/pubmed/8257864
(29)
http://www.ncbi.nlm.nih.gov/pubmed/23214067
(30)
http://www.bprcem.com/article/S1521-690X%2807%2900026-7/abstract
(31)
http://www.hotthyroidology.com/editorial_79.html
(32)
http://www.ncbi.nlm.nih.gov/pubmed/8475937
(33)
http://jcem.endojournals.org/content/84/2/401.full
Euthyroid sick syndrome
Euthyroid sick syndrome is defined as a condition of low T
3 low T
4 syndrome. According ot the study by the Mayo Clinic, in other word this is the abnormalities of
thyroid hormone
concentrations seen commonly in a wide variety of nonthyroidal
illnesses, resulting in low triiodothyronine, total thyroxine, and
thyroid stimulating
hormone concentrations(a). Decreased triiodothyronine (T
3) levels are most common. Patients with more severe or prolonged illness also have decreased thyroxine (T
4) levels. Serum reverse T
3 (rT
3) is increased. Patients are clinically euthyroid and do not have elevated thyroid-stimulating hormone (TSH) levels(b). Causes of euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, sepsis, trauma, cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, chronic renal failure, cirrhosis, and diabetic ketoacidosis and inflammatory bowel disease(c). Others, in the study of classified
SES into 3 subgroups according to the different alterations seen in the values of T3, T4, FT3, FT4, TSH, rT3 and TBG suggested that in
SES type I
the diseases seen, in order of frequency, were: obstructive chronic
bronchopneumopathy with acute respiratory failure, diabetic
ketoacidosis,
neoplasms,
ischemic heart disease, cardiac failure, chronic renal failure, liver
diseases, acute cerebral vasculopathies, sepsis and collagenopathies.
The disease seen in the 2 cases of
SES type II was obstructive chronic bronchopneumopathy with acute respiratory failure. In
SES
type III the diseases seen were, in order of frequency: diabetic
ketoacidosis, lung diseases, ischemic heart disease, cardiac failure,
peripheral arteriopathies, acute cerebral vasculopathies,
neoplasms, liver diseases, acute renal failure(d).
Euthyroid sick syndrome as a result of pneumonia
Pneumonia is defined as a condition of the inflammation of the lung as a result of infection, caused by bacteria, such as bacteria Streptococcus pneumoniae or influenza viruses in most cases. Fungi, such as Pneumocystis jiroveci, certain medication such as PPI Stomach Acid Drugs and other conditions such as impaired immune systems.
According to Author: V. Dimov, M.D. and S. Randhawa, M.D. There is report of a 57-year-old female with a past medical history (PMH) of SLE,
hypertension (HTN) and depression was transferred from an outside
hospital for work-up and treatment of a change in mental status and
fever. That admission was preceded by a one-week history of diffuse
joint pain, weakness, and fatigue. On transfer, she was diagnosed with multilobar pneumoni...(1).
1. Pneumonia - Viral causes of Pneumonia
2.
Pneumonia - Bacterial causes of Pneumonia
3.
Fungi and parasites causes of Pneumonia
4.
Pneumonia - The Risk factors
5. Pneumonia - The Misdiagnosis
6.
Pneumonia - Diseased associated to pneumonia
7. Pneumonia - The Complications
8.
Pneumonia - The Diagnosis
9. Preventions
9.1.
Pneumonia Preventions- The do and do not's list
9.2.
Diet to prevent pneumonia
9. 3. Phytochemicals to prevent pneumonia
9.4.
Antioxidants to prevent pneumonia
10. Treatments
10.1. Pneumonia Treatments In conventional medicine perspective
10.2.
Pneumonia Treatments In Herbal medicine perspective
10.3. Pneumonia Treatments In traditional Chinese medicine perspective
Sepsis
Sepsis is defined as a condition caused by chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body as a result of severe infection(a)(b). according to the study by the University of Utah, s
epsis is the commonest cause of admission to medical ICUs across the world. Mortality from
sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to
sepsis, complications arising from
sepsis-related immunoparalysis contribute to the morbidity and mortality from
sepsis(c).
A. Symptoms
1. Chilly periphery, fever, jaundice, platelet and hemoglobin
I(n the study to o explore the risk factors, clinical symptoms, hematological parameters,
causative pathogen and antibiotic susceptibility of neonatal
sepsis in a Chinese NICU, found that the clinical symptoms or laboratory results such as chilly periphery,
fever,
jaundice, platelet and hemoglobin also had between-group differences.
The most common responsible pathogenic bacteria species present in EOS
group was Coagulase-negative Staphylococcus (CoNS)(1).
2. Abnormalities of blood pressure, respiration, temperature, and heart rate, and less well-known changes in heart rate variability
Early detection of late-onset neonatal
sepsis, before the onset of obvious and potentially catastrophic clinical signs, is an important goal in neonatal medicine.
Sepsis causes a well-known series of physiologic changes including abnormalities of blood pressure, respiration, temperature, and
heart rate, and less well-known changes in
heart rate variability, according to the University of Virginia(2).
3. Significantly decreased urine output but accumulative fluid balance had a weak correlation with delta sequential
organ failure assessment score (r = 0.32, P = 0.001) and lung injury
score (r = 0.13, P = 0.02) and negative correlation with PaO2/FIO2 ratio
(r = -0.28, P = 0.001)(3).
4. Abrupt change in mental status, difficult breathing and abnormal blood circulation
Early recognition of
sepsis
and septic shock in children relies on obtaining an attentive clinical
history, accurate vital signs, and a physical examination focused on
mental status, work of breathing, and circulatory
status, according to the study by the University of Colorado School of Medicine(4).
B. Causes and Risk factors
B.1. Causes
1. Bacteria infection
In the study of Neonates admitted to the neonatal intensive care unit (NICU) at National
Taiwan University Hospital (NTUH) between January 2001 and December
2006, found that in n early-onset
sepsis,
the most common pathogens responsible included group B streptococci
(GBS) (36%) and Escherichia coli (E. coli) (26%). GBS was associated
with more meningitis involvement but lower incidence of mortality
compared with E. coli. The most common causative microorganisms in
late-onset
sepsis were coagulase-negative staphylococci (CONS) (40%) and Candida (15%). The
sepsis-related mortality rates were higher in early-onset
sepsis (10%) than in late-onset
sepsis (7%)(5).
Other study indicated that Burkholderia cepacia has rarely been reported in Honolulu. Its emergence
as a nursing home-acquired pathogen with high mortality rate is
concerning. This
case report describes a local nursing home patient who was diagnosed with B. cepacia
sepsis in 2012(6).
2. Renal infection (Acute pyelonephritis (APN))
IOn the study to assess the risk factors for septic shock by multivariate logistic regression analysis of 69 patients with obstructive APN associated with upper urinary tract calculi who were admitted to the hospital, indicated that patients with obstructive APN associated with upper urinary tract
calculi who have decreases in platelet count and serum albumin level
should be treated with caution against the development of septic shock(7).
3. Pneumonia
Klebsiella (K.) pneumoniae is a common cause of
pneumonia-derived
sepsis, according to the study by the University of Amsterdam(8).
4. Bloodstream infection
In the study to determine the independent risk factors on mortality in patients with community-acquired severe
sepsis and septic shock, found that in addition to the severity of illness, hypoalbuminemia was identified as
the most important prognostic factor in community-acquired
bloodstream infection with severe
sepsis and septic shock(9).
5. Abdominal infection
In the study to investigate the alteration of complement system in patients with severe
abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients, indicated that complement C3 depletion was found to be connected to poor prognosis in severe
abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated
infection during
sepsis, which should be paid close attention in critical care(10).
6. Dementia in elders
In the
population-based
cohort study, in analyzing 41,672 older (≥ 65 years) patients, including
3,487 (8.4%) with dementia, from the first-time admission claim data
between 2005 and 2007 for a nationally representative sample of one
million beneficiaries enrolled in the Taiwan National Health Insurance
Research Database, found that In hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe
sepsis
and hospital mortality. However, after intervention using life-support
treatments, dementia only exhibited a minor role on short-term
mortality(11).
7.
Drug-resistant bacteria
In the study to identify the frequency of bacterial isolates in early-onset neonatal
sepsis (EONS) and their antimicrobial
resistance pattern, found that K. pneumoniae was the predominant causative
bacteria of EONS followed by E. cloacae and E. coli. There was a high
resistance to ampicillin. Imipenem had the maximum overall activity against the causative
bacteria. Continuous surveillance is needed to monitor the changing epidemiology of pathogens and antibiotic sensitivity(12).
8.
Weakened immune systems
Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the
immune response to
sepsis provide the opportunity to develop more effective therapies. The
immune response in
sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent
immune-suppressive
phase. Patients fail to eradicate invading pathogens and are
susceptible to opportunistic organisms in the hypo-inflammatory phase.
Many mechanisms are responsible for
sepsis-induced immuno-suppression, including apoptotic depletion of
immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion(13).
B.2. Risk factors
1. Term infants, while very low birth weight (VLBW) and preterm infants
According to the study by the Taipei City Hospital, total of 109 episodes of
sepsis were identified in 100 neonates. The incidence of
sepsis was 4.06% among all NICU admissions. Most neonates with early-onset
sepsis were term infants, while very low birth weight (VLBW) and preterm infants accounted for the majority of cases of late-onset
sepsis(14).
2. Obesity, operative vaginal delivery and age <25 years
In the study to describe the risk of maternal
sepsis associated with obesity and other understudied risk factors such as operative vaginal delivery, found that ontrolling for mode of delivery and demographic and clinical factors, obese women had twice the odds of uncomplicated
sepsis
(OR 2.12; 95% CI 1.14-3.89) compared with women of normal weight. Age
<25 years (OR 5.15; 95% CI 2.43-10.90) and operative vaginal delivery
(OR 2.20; 95% CI 1.02-4.87) were also significant predictors of
sepsis. Known risk factors for maternal
sepsis were also significant in this study (OR for uncomplicated and severe
sepsis
respectively): multiparity (OR 6.29, 12.04), anaemia (OR 3.43, 18.49),
labour induction (OR 3.92 severe only), caesarean section (OR 3.23,
13.35), and preterm birth (OR 2.46 uncomplicated only)(15).
3. Elder
If you are elder, you are at increased risk of sepsis
4. Patient in intensive care and with weakened immune system
Intra-abdominal infections are a common problem for the general surgeon
and major sources of morbidity and mortality in the intensive care unit(16). Other indicated that severe
sepsis has emerged as a major cause of admission and mortality for hospitalized
HIV/AIDS patients, significantly affecting short- and longer-term survival of critically ill
HIV/AIDS patients(17).
5. Invasive devices
There is a study of indwelling
intravenous polyethylene
catheters as factors influencing the risk of microbial colonization and
sepsis(18).
6. Obesity and alcpholism
A multivariate analysis revealed that obesity (adjusted odds ratio [aOR]
21.4; 95% confidence interval [CI] 1.8-257.5) and alcoholism (aOR 6.5;
95% CI 1.3-32.8) were important predictive factors for spinal
sepsis(18a).
C. Complications and diseases associated to Sepsis
C.1. Complcations
1. Impaired wound healing
Sepsis is one of the main
causes for morbidity and mortality in hospitalized patients. Moreover,
sepsis associated complications involving impaired wound healing are common(19).
2. Damage to Peripheral nerves and skeletal muscles
Among the
critical illness myopathies, three main types have been identified: a non-necrotizing "cachectic" myopathy (
critical illness
myopathy in the strict sense), a myopathy with selective loss of myosin
filaments ("thick filament myopathy") and an acute necrotizing myopathy
of intensive care. Clinical manifestations of both
critical illness myopathies and CIP include delayed weaning from the respirator, muscle weakness, and prolonging of the mobilization phase, according to the study by Ruprecht-Karls University, Heidelberg(20).
3. Organs failure
Bacterial translocation is the invasion of indigenous intestinal
bacteria through the gut mucosa to normally sterile tissues and the
internal
organs. Bacterial translocation may be a normal phenomenon occurring on frequent
basis in healthy individuals without any deleterious consequences. But
when the immune system is challenged extensively, it breaks down and
results in septic complications at different sites away from the main
focus. The factors released from the gut and carried in the mesenteric
lymphatics but not in the portal blood are enough to cause multi-organ
failure, according to Postgraduate Institute of Medical Education and Research(21).
4. Morbidity and mortality
Acute kidney injury (AKI) is a common and often catastrophic complication
in hospitalized patients; however, the impact of AKI in surgical
sepsis
remains unknown. We used Risk, Injury, Failure, Loss, End stage (RIFLE)
consensus criteria to define the incidence of AKI in surgical
sepsis and characterize the impact of AKI on patient morbidity and
mortality(22). Other study indicated that in patients with
sepsis who are admitted to an ICU, cardiac troponin T elevations are independently
associated with in-hospital and short-term mortality but not long-term mortality(23).
C.2.
Diseases associated to Sepsis
1. Staphylococcal infections
Preterm infants are especially susceptible to late-onset
sepsis that is often due to Gram-positive bacterial
infections resulting in substantial morbidity and mortality(24).
2. Elevated central venous pressure
Elevated central venous
pressure is associated with impairment of microcirculatory
blood flow in
sepsis(25).
3. Neonatal cellulitis
there is a report of a case of late onset neonatal invasive group A streptococcal disease characterized with rapidly progressing cellulitis and development of sepsis(26).
4. Methicillin-resistant Staphylococcus aureus
There is a report of the spectrum of community-acquired S. aureus infections and to compare the patients infected with methicillin-susceptible or methicillin-resistant strains among patients aged <20 years. Overall, 90 cases of community-acquired S. aureus were detected in an 11-year period(27).
5. Bladder infection
Bladder bacteria is common but unique cause for
sepsis(28).
6. Urinary tract infection
In the study to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants, found that seven days of Lactobacillus GG supplementation starting with the first
feed is not effective in reducing the incidence of UTIs, NEC and
sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations(29).
7. Venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus)
According to the study b ythe UC Davis School of Medicine, there was increased risk of AbVTE early (<90 days; hazard ratio [HR]
5.4 [confidence interval (CI), 2.3-12.5]), but not late (≥90 days; HR
1.5 [CI, 0.9-2.6]) after splenectomy. There was increased risk of VTE
both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after
splenectomy. The cumulative incidence of
sepsis
was 11.1% among the ITP patients who underwent splenectomy and 10.1%
among the patients who did not. Splenectomy was associated with a higher
adjusted risk of
sepsis,
both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on
comorbidities). ITP patients post splenectomy are at
increased risk for AbVTE, VTE, and
sepsis(30).
8. Hydroureteronephrosis
Hydroureteronephrosis without vesicoureteral reflux or
lower-urinary-tract obstruction is uncommon in infants. There has been
considerable interest in and controversy over the cause and management
of this entity. We have cared for three neonates with severe
hydroureteronephrosis after acute urinary tract infections, who were
treated without operation, according to Pais VM, and Retik AB(31).
9. Osteomyelitis
Sepsis and osteomyelitis about the ankle joint present a challenging clinical problem. Osteomyelitis
usually follows open fracture of the distal tibia, often with a pilon
fracture component. Treatment of subsequent osteomyelitis and sepsis,
including the authors' experiences, is discussed. Septic ankle
arthritis can occur hematogenously. In some patients, the optimal
treatment for concomitant osteomyelitis and sepsis is a below knee amputation(32).
10. Necrotizing fasciitis
There is a report of a case of necrotizing fasciitis and
sepsis caused by Aeromonas hydrophila after crush injury of the lower extremity(33).
11. Phlebitis
There is a report of a case of Septic pulmonary emboli secondary to internal jugular vein
phlebitis (postanginal
sepsis) caused by Eikenella corrodens(34).
12. Lymphedema
There is a report of a patient with congenital penoscrotal
lymphedema complicated by cellulitis, lymphangitis, and severe
sepsis
associated with a streptococcal infection. This case represents the
importance of obtaining a detailed clinical history and physical
findings(35).
13. Vancomycin-Resistant Enterococci (VRE)
The prevalence of the VRE that caused bacteraemia increased from 2003 to
2010. This increase might be attributed to the clonal spread of VREfm
belonging to ST18 and ST414. The all-cause 14 day mortality rate was
lower in patients with bacteraemia due to VREfm isolates that belonged
to ST414(36).
D. Misdiagnosis and diagnosis
D.1. Misdiagosis
1. Delayed diagnosis
There is a report of encountered a
case where the diagnosis of malarial infection in a woman with acute puerperal
sepsis was significantly delayed(37). Others report a case of Necrotizing fasciitis (NF), a rare polymicrobial infection that can be
life-threatening. It is a rapidly progressive inflammatory process
affecting the deep fascia, with secondary necrosis of the subcutaneous
tissue.
Misdiagnosis and delayed treatment can result in death from
sepsis, mediastinitis, carotid artery erosion, jugular vein thrombophlebitis, or aspiration pneumonia(38).
2. Delirium
There is a report of three cases of a 65-year-old woman, admitted
for malnutrition, has significant mood-related symptoms that resemble
depression, a 50-year-old male, admitted with an abscess, necrotizing
fasciitis and
sepsis,
appears to be suicidal and 61-year-old male, admitted with pneumonia,
has auditory hallucinations. All three patients turned out to have a
delirium(39).
3. Fatal sepsis
There is a report of a case of fatal
sepsis
caused by infection with Klebsiella variicola, which is an isolate
genetically related to Klebsiella pneumoniae. The patient's condition
was incorrectly diagnosed as common
sepsis
caused by K. pneumoniae, which was identified using an automated
identification system, but next-generation sequencing and the
non-fermentation of adonitol finally identified the cause of
sepsis as K. variicola(40).
4. Shigella sonnei
There is a report of a
case of
sepsis,
caused by a commensal inactive Escherichia coli, which had been
repeatedly misidentified as Shigella sonnei by VITEK 2 compact(41).
D.2. Diagnosis
According to the study by the Mustafa Kemal University, in cases of severe
sepsis and septic shock, lactate clearance early in the hospital course may indicate a resolution
of global tissue hypoxia and is associated with decreased
mortality
rate. Patients with higher lactate clearance after 6 hrs of emergency
department intervention have improved outcome compared with those with
lower lactate clearance(42).
If you are experience certain symptoms of the above and your doctor suspects that you have developed
Sepsis, after
recording the past and present history and completing a physical
exam, the
tests which your doctor orders
may include
1. The table of sepsis diagnostic criteria
Table 1. Diagnostic criteria for sepsis
[Levy
M, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM,
Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis
Definitions Conference. Crit Care Med 2003;31:1250-6]
| Infection, documented or suspected*, and some of the following: |
| General variables |
Fever (> 38.3 °C)
Hypothermia (< 36 °C)
Tachycardia (heart rate > 90/min, or >2 SD above the normal value for age)
Tachypnea (increased respiratory rate)
Altered mental status
Significant edema or positive fluid balance (> 20 mL/kg over 24 hrs)
Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetes
|
| Inflammatory variables |
Leukocytosis (WBC count > 12,000/uL
Leukopenia (WBC count < 4,000/uL
Normal WBC count with > 10% immature forms
Elevated plasma C-reactive protein (CRP)
Elevated plasma procalcitonin (PCT)
|
| Hemodynamic variables |
Arterial hypotension
SvO2 (mixed venous oxygen saturation) > 70%
Elevated cardiac index (>3.5 L/min/m2)
|
| Organ dysfunction variables |
Arterial hypoxemia
Acute oliguria (reduced urine output)
Creatine increase
Coagulation abnormalities (elevated D-dimer, prolonged PT, reduced protein C)
Ileus (absent bowel sound)
Thrombocytopenia (platelet count < 100,000/uL)
Hyperbilirubinemia
|
| Tissue perfusion variables |
Elevated blood lactate
Decreased capillary refill or mottling
|
(44).
2. The Laboratory tests
The aim is the test is to identify the infectious agent causing the infections. According to the study by the Stanford University School of Medicine, definitive diagnosis depends on cultures of blood or other normally
sterile body fluids. Abnormal hematological counts, acute-phase
reactants, and inflammatory cytokines are neither sensitive nor
specific, especially at the onset of illness. Combinations of
measurements improve diagnostic test performance, but the optimal
selection of analytes has not been determined. The best-established use
of these
laboratory tests
is for retrospective determination that an infant was not infected,
based on failure to mount an acute-phase response over the following 24
to 48 hours(43).
E. Preventions
E.1. Diet to prevent sepsic
1.
Onions
The onion is a plants in the genus
Allium, belongs to the family Alliaceae, a close relation of garlic. It
It is often called the "king of vegetables" because of its pungent
taste and found in a large number of recipes and preparations spanning
almost the totality of the world's cultures. Depending on the variety,
an onion can be sharp, spicy, tangy, pungent, mild or sweet. Since it contains high amount of antioxidants, onion enhances the
immune system in fighting against the forming of free radicals and
foreign invasion, thus eeducing the symptoms of inflammatory conditions
such as arthritis and gout and infection caused by bacteria, including
E.coli and salmonella,etc., according to the study of Antibacterial
and
antioxidant activities of quercetin oxidation products from yellow
onion (Allium cepa) skin." by Ramos FA, Takaishi Y, Shirotori M, Kawaguchi
Y, Tsuchiya K, Shibata H, Higuti T, Tadokoro T, Takeuchi M., posted in
PubMed(45).
2. Blueberries
Blueberry
is a flower plant, belong to the family Eriaceae and native to
Northern America. It can grows from 10 cm to 4 meters tall.
a. Antioxidant Capacity
In the investigation of Blueberry
and blackberry wines commercially available in Illinois and theirs
potential health benefits, found that fruit wines made from
blueberries
and blackberries may have potential health applications and therefore
could contribute to the economy of the wine industry. Practical
Application: The majority of wines are produced from grapes, but wine
can also be produced from other fruits including
blueberries and blackberries, which contain phenolic compounds that may contribute to human health, according to "
Comparison of Chemical Composition and Antioxidant Capacity of Commercially Available Blueberry and Blackberry Wines in Illinois" by Johnson MH, Gonzalez de Mejia
E.(46).
b. Inflammatory bowel diseases
In the study of blueberries and broccoli in mdr1a(-/-) mice (IBD mouse model) for theirs effect gastrointestinal tract, found that
blueberry-
and broccoli-supplemented diets increased colon crypt size and the
number of goblet cells per crypt. Only the broccoli-supplemented diet
significantly lowered colonic inflammation compared to mice fed the
control diet, according to "
Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in mdr1a(-/-) mice, a model of inflammatory bowel diseases" by Paturi G, Mandimika T, Butts CA, Zhu S, Roy NC,
McNabb WC, Ansell J.(47).
3. Mushroom
Mushroom is a standard name of white button
mushroom, the fleshy, spore-bearing fruiting body of a fungus produced
above ground on soil or on its food source, It is a genus A. Muscaria
and belong to the family Amanitaceae and has been cultivation in many cultures all over the world for foods and health benefits.
In the analyzing White button mushrooms (WBM) and its effect in immune response, found that WBM
promote DC maturation and enhance their antigen-presenting function.
This effect may have potential in enhancing both innate and T
cell-mediated immunity leading to a more efficient surveillance and
defense mechanism against microbial invasion and tumor development,
according to "White button mushroom enhances maturation of bone marrow-derived dendritic cells and their antigen presenting function in mice" by Ren Z, Guo Z, Meydani SN, Wu D.(48).
4. Green Tea
a. Immune system
In the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK(49), researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout.
b. Antimicrobial activities
a. In the investigation of Antimicrobial
activities of green of the study of "
Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus"
by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N.(50),
researchers found that flavonoids in green tea has exerted its ability
in protective effects against Bacillus cereus.
2. Phytochemicals and antioxidants to prevent sepsis
1. Vitamin A and Immunity as antioxidants
Vitamin A occurs in the form retinol and is best known for its function
in maintaining the health of cell membrane, hair, skin, bone, teeth
and eyes. It also plays an important role as an antioxidant as it
scavenges free radicals in the lining of the mouth and lungs; prevents
its depletion in fighting the increased free radicals activity by
radiation; boosts immune system in controlling of free radicals;
prevents oxidation of LDL and enhances the productions of insulin
pancreas(51).
2.
High dose of vitamin C and Immune system
In the first comparative analysis of the ex vivo and in vitro molecular and
cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP, found that in comparison to IFN-α, high-dose AA treatment has superior ex vivo and
in vitro cell death-inducing, antiproliferative and immunomodulatory
anti-HTLV-1 effects. Differential pathway activation by both drugs opens
up avenues for targeted treatment in specific patient subsets(52).
3. Vitamin E and Immunity
Vitamin E is the most important chain-breaking, lipid-soluble
antioxidant present in body tissues of all cells and is considered the
first line of defense against lipid peroxidation and it is important for
normal function of the immune cells. However, vitamin E deficiency
is rare in well-nourished healthy subjects and is not a problem, even
among people living on relatively poor diets, both T- and B-cell
functions are impaired by vitamin E deficiency. While immune
cells are particularly enriched in vitamin E because of their high
polyunsaturated fatty acid content, this point puts them at especially
high risk for oxidative damage, according to the study by Dr. Pekmezci D. at the University of Ondokuz Mayıs(53).
4. Allyl sulfides and Immune system
According
to the article of "GARLICTHE BOUNTIFUL BULB" by Carmia Borek, Ph.D.
posted in Life extension magazine, the author indicated that human
studies confirm immune stimulation by garlic. Subjects receiving aged
garlic extract at 1800 mg a day for three weeks showed a 155.5%
increase in natural killer immune cell activity that kills invaders and
cancer cells. Other subjects receiving large amounts of fresh garlic
of 35g a day, equivalent to 10 cloves, showed an increase of 139.9%.
In six weeks, patients with AIDS receiving aged garlic extract showed
an enhancement of natural killer cells from a seriously low level to a
normal level(54).
5. Allicin is phytochemical containing sulfur in the class of organosulfur compound, found abundantly in onion and garlic.
Antibacterial activities
In the comparison of those of allicin
and several clinically useful antibiotics using two representative
bacteria commonly found in the human environment, Gram-positive S.
aureus and Gram-negative Escherichia coli, indicated that The garlic
extract had more potent anti-staphylococcal activity than an equal
amount of allicin. In terms of antibiotic potency against Gram-positive and Gram-negative bacteria, authentic allicin
had roughly 1-2% of the potency of streptomycin (vs. S. aureus), 8%
of that of vancomycin (vs. S. aureus), and only 0.2% of that of
colistin (vs. E. coli), according to "Antibacterial potential of garlic-derived allicin and its cancellation by sulfhydryl compounds" by Fujisawa H, Watanabe K, Suma K, Origuchi K, Matsufuji H, Seki T, Ariga T.(54).
6. Cinnamon
a. Immunomodulatory effect
In
administration of popular herb used in traditional medicine to treat
various disorders such as chronic gastric symptoms, arthritis, and the
common cold and its immunomodulatory effect found that observations
provided evidence that CWE was able to down-regulate IFN-γ expression
in activated T cells without altering IL-2 production, involving
inhibition of p38, JNK, ERK1/2, and STAT4, according to the study of "Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation" by Lee BJ, Kim YJ, Cho DH, Sohn NW, Kang H.(55)
b. Antimicrobial Activities
In the observation of three natural essential oils (i.e., clove bud oil, cinnamon oil, and star anise oil) and their antimicrobal effects found that the cinnamon
oil-chitosan film had also better antimicrobial activity than the
clove bud oil-chitosan film. The results also showed that the
compatibility of cinnamon oil with chitosan in film formation was better than that of the clove bud oil with chitosan, according to the study of "Synergistic Antimicrobial Activities of Natural Essential Oils with Chitosan Films" by Wang L, Liu F, Jiang Y, Chai Z, Li P, Cheng Y, Jing H, Leng X.(56)
c. Anti-inflammatory activity
In
the investigation of Myristicin
(1-allyl-5-methoxy-3,4-methylenedioxybenzene) is an active aromatic
compound found in nutmeg (the seed of Myristica fragrans), carrot,
basil,cinnamon,
and parsley and it anti-inflammatory effects found that Myristicin
significantly inhibited the production of calcium, nitric oxide
(NO),interleukin (IL)-6, IL-10, interferon inducible protein-10,
monocyte chemotactic protein(MCP)-1, MCP-3, granulocyte-macrophage
colony-stimulating factor, macrophage inflammatory protein (MIP)-1α,
MIP-1β, and leukemia inhibitory factor in
dsRNA[polyinosinic-polycytidylic acid]-induced RAW 264.7 cells (P <
0.05), according to the study of "Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinic-polycytidylic acid" by Lee JY, Park W.(57)
F. Treatments
E.1. Treatments in conventional medicine perspective
1. Antibiotics
Most case of sepsis are treated with combination of two or three antibiotics given at the same time.
High doses of
vancomycin
were administered in order to rescue patients from septic shock. Plasma
drug concentration dropped while clinical condition of patients
worsened. Conversely, drug levels increased spontaneously once the
infection was reverted. The theoretical model provided greater insight
into pharmacokinetic features related with the use of
vancomycin in septic patients(58). Other study indicated that patients with
sepsis
do not seem to have the same level of impairment of tissue distribution
as described for patients with septic shock. A 25% lower dose of
piperacillin administered by continuous infusion seems to maintain
higher trough concentrations compared with standard bolus dosing. It is
likely that the clinical advantages of continuous infusion are most
likely to be evident when treating pathogens with high minimum
inhibitory concentration, although without therapeutic drug monitoring
and subsequent dose adjustment, infusions may never achieve target
concentrations of organisms with very high minimum inhibitory
concentrations in a small number of patients(59).
2. IV Fluids
In the study to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe
sepsis, found that continuous administration of beta-lactam
antibiotics
achieved higher plasma antibiotic concentrations than intermittent
administration with improvement in clinical cure. This study provides a
strong rationale for further multicenter trials with sufficient power to
identify differences in patient-centered endpoints(60). Other study suggested that routine use of prolonged infusion of time-dependent
antibiotics
for the empiric treatment of gram-negative bacterial infections offers
no advantage over intermittent infusion antibiotic therapy with regard
to treatment success, mortality, or hospital length of stay. These
results were confirmed after controlling for potential confounders in a
multivariate analysis(61).
E.2. Treatments in herbal medicine perspective
1. Taraxacum coreanum
Taraxacum coreanum Nakaiis a dandelion native to Korea and is widely consumed as an edible and medicinal
herb. Treatment of primary macrophages with Taraxacum coreanum chloroform fraction(TCC) in vitro significantly
inhibited all of the inflammatory parameters measured, including
LPS-induced NO and PGE2 production, iNOS and COX-2 expression, IκBα
degradation, IKK phosphorylation, and MAPK and STAT1 activation. In a
mouse model of LPS-induced septic shock, TCC inhibited the production of
tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and
increased survival by 83%.Standard compounds (gallic acid, syringic
acid) of Taraxacum coreanum were qualified by HPLC analysis, according to Kyung Hee University(62).
2. Chamaecyparis obtusa
β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. According to the study by the Chia-Nan University of Pharmacy and Science, the potential of β-thujaplicin in treatment of inflammation and
sepsis.
These effects occur through an efficient blockage of TNF-alpha and iNOS
production. β-thujaplicin efficacy is comparable to that of
indomethacin thus it can be a substitution but bear less depletion of
PGE2, making this compound very promising in clinical applications(63).
3. Angelica sinensis
A low-molecular-weight (<10 kDa) fraction of A. sinensis extract
significantly attenuated endotoxin-induced HMGB1 release in part through
interfering with its cytoplasmic translocation in macrophage cultures.
Prophylactic administration of an aqueous extract of A. sinensis
significantly attenuated systemic HMGB1 accumulation in vivo, and
conferred a dose-dependent protection against lethal endotoxemia.
Furthermore, delayed administration of A. sinensis extract beginning 24 h
after CLP attenuated systemic HMGB1 accumulation, and significantly
rescued mice from lethal
sepsis.
Taken together, these data suggest that A. sinensis contains
water-soluble components that exert protective effects against lethal
endotoxemia and experimental
sepsis in part by attenuating systemic accumulation of a late proinflammatory cytokine, HMGB1, according to the New York University School of Medicine(64).
4. Green tea
Intraperitoneal administration of EGCG protected mice against lethal endotoxemia, and rescued mice from lethal
sepsis
even when the first dose was given 24 hours after cecal ligation and
puncture. The therapeutic effects were partly attributable to: 1)
attenuation of systemic accumulation of proinflammatory mediator (e.g.,
HMGB1) and surrogate marker (e.g., IL-6 and KC) of lethal
sepsis;
and 2) suppression of HMGB1-mediated inflammatory responses by
preventing clustering of exogenous HMGB1 on macrophage cell surface, according to the study by the North Shore University Hospital-New York University School of Medicine(65).
E.3. Treatments in traditional Chinese medicine perspective
1. Cortex lycii Cortex lycii with both highest affinities was selected out from one hundred and fourteen traditional Chinese herbs. In subsequent experiments, chromatography was utilized and coupled with
the biosensor to purify fractions with a higher affinity for LPS and
CpG DNA. In line with affinity assay, these fractions were shown to
neutralize LPS and CpG DNA and inhibit their activity in vitro and in
vivo. Lastly, the contributing monomer Kukoamine B (KB) was purified. KB
neutralized LPS and CpG DNA in vitro. It inhibited TLR4, TLR9 and MyD88
mRNA expressions up-regulated by LPS and CpG DNA, and also attenuated
the LPS and CpG DNA elicited nuclear translocation of NF-κB p65 protein
in RAW264.7 cells. It also protected mice from lethal challenge of
heat-killed E. coli, a mixture of LPS and CpG DNA(66).
2. Magnolia officinalis
Magnolol is a compound extracted from the Chinese medicinal
herb Magnolia officinalis. In the study to evaluate the effects of magnolol on
sepsis
induced by intravenous (i.v.) administration of lipopolysaccharide
(LPS; 10 mg/kg) in anaesthetized Wistar rats with Magnolol (4 microg/kg,
i.v.) was administered at 30 min after LPS injection, found that post-treatment with magnolol significantly attenuated the deleterious
haemodynamic changes (e.g., hypotension and bradycardia) caused by LPS.
Meanwhile, magnolol significantly inhibited the elevation of plasma
levels of tumor necrosis factor alpha, glutamate-oxaloacetate
transaminase, glutamate-pyruvate transaminase and blood urine nitrogen
caused by LPS. The induction of inducible nitrous oxide (NO) synthase
and the overproduction of NO and superoxide anions by LPS were also
significantly reduced by post-treatment with magnolol. Moreover, the
plasma level of the thrombin-antithrombin complex following
administration of LPS was also reduced by post-treatment with magnolol(67).
3. Terminaliachebula Retz
Terminaliachebula Retz was found to possess the highest capability of
binding lipid A. With CER (cation-exchange resin) and HPLC, the extracted from Terminaliachebula Retz, and named
them TCR1, TCR2 and TCR3 respectively was found that the TCR3 was the
most capable candidate to bind lipid A. We also studied the biological
activities of TCR3 against
sepsis
in vitro and in vivo. in vitro, TCR3 could significantly inhibit LPS
(lipopolysaccharide)-induced LAL (Limulus amoebocyte lysate)) from
agglutination and decrease TNFalpha (tumour necrosis factor alpha)
release from RAW264.7 cells induced by LPS in a dose-dependent manner.
in vivo, TCR3 could significantly protect mice against a lethal
challenge with LPS and heat-killed Escherichia coli 35218 in a
dose-dependent manner(68).
4. Scutellaria baicalensis Georgi (Huang Qin)
2',5,6',7-tetrahydroxyflavanonol (THF) from S. baicalensis Georgi under
the direction of neutralization of LPS and reducing proinflammatory
cytokines. In vitro, THF directly bound to LPS and neutralized its
activity. THF not only down-regulated TNF-alpha mRNA expression but also
decreased TNF-alpha and IL-6 release from RAW264.7 cells induced by LPS
in a dose-dependent manner. THF-mediated inhibition on proinflammatory
cytokine release is probably associated with downregulation of
LPS-induced TLR4 mRNA augmentation. In vivo, THF could significantly
protect mice against a lethal challenge with heat-killed E. coli 35218
(E. coli 35218) in a dose-dependent manner, and decreased the plasma LPS
level in endotoxemia mice, according to Third Military Medical University(69).
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http://www.ncbi.nlm.nih.gov/pubmed/1089891
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http://www.ncbi.nlm.nih.gov/pubmed/11232476
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http://www.ncbi.nlm.nih.gov/pubmed/18687029
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http://www.ncbi.nlm.nih.gov/pubmed/6383158
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http://www.ncbi.nlm.nih.gov/pubmed/22618861
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http://www.ncbi.nlm.nih.gov/pubmed/24032986
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http://www.ncbi.nlm.nih.gov/pubmed/23790808
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http://www.ncbi.nlm.nih.gov/pubmed/23449877
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http://www.ncbi.nlm.nih.gov/pubmed/22029193
(42)
http://www.ncbi.nlm.nih.gov/pubmed/15286537
(43)
http://www.ncbi.nlm.nih.gov/pubmed/20569816
(44)
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http://www.ncbi.nlm.nih.gov/pubmed/19127724
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http://www.ncbi.nlm.nih.gov/pubmed/21985858
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Sources
(a)
http://www.ncbi.nlm.nih.gov/pubmed/9086580
(b)
http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/thyroid_disorders/euthyroid_sick_syndrome.html
(c)
http://en.wikipedia.org/wiki/Euthyroid_sick_syndrome
(d)
http://www.ncbi.nlm.nih.gov/pubmed/8028742
(1)
http://clinicalcases.org/2004/05/sick-euthyroid-syndrome-in-patient-with.html
Malignancy
Malignancy is defined as a medical condition of the the cells of the body have become cancerous, with the tendency to spread to other part of the body. For most comon types of cancer, please visit
*What is Cancer
Euthyroid sick syndrome and cancers
1. Euthyroid sick syndrome and Skin cancer
2. Euthyroid sick syndrome and
bone or soft tissue cancers
According to the study by the University Hospital, Rotterdam,
Cytokines have been implicated in the pathogenesis of the euthyroid sick
syndrome. Isolated limb perfusion (ILP) with recombinant human tumor
necrosis factor alpha (rTNF) and melphalan in patients with melanoma or
sarcoma is accompanied by high systemic(1) http://www.ncbi.nlm.nih.gov/pubmed/10094108
*Bladder Cancer
*Bladder Cancer In Traditional Chinese Medicine Perspective
*Bone Cancer (Osteosarcoma and Other Types)
*Bone Cancer In Traditional Chinese Perspective
Brain and Spinal Cord Cancer
Cancer of Esophagus/Esophageal Cancer
*Cervical Cancer
Bowel Cancer (Colon and rectum)
*Breast Cancer
*Cancer with unknown primary site (CUP)
*Choriocarcinoma and Hydatidiform Mole(Tumors and Placenta)
*Cancer of Endometrium ( Womb)
*Esophagueal cancer
*Hodgkin's diseases
*Kaposi's Sarcoma
*Kidney Cancer (Renal cell Carcinoma)
*Larynx (Voice Box) Cancer/Laryngeal Cancer
Pharynx (Throat) Cancer
Leukemias
*a. Lymphoblastic leukemia- Chronic lymphoblastic leukemia (CLL)
b. Myelogenous leukemia - Chronic myelogenous leukemia (CML)
c. Lymphoblastic leukemia - Acute lymphoblastic leukemia (ALL)
d. Myelogenous leukemia - Acute myelogenous leukemia (AML)
Liver Cancer (Hepatocellular carcinoma)
*Lung cancer
(Non-small-cell and small cell lung cancer)
*Lymphoma (No-Hodgkin's Lymphoma(The Indolent Lymphomas and The high grade Lymphomas)
*Melanoma skin cancer ( Malignant Melanoma)
*Mouth ( Oral ) cancer
*Myeloma (Multiple Myenoma)
Ovary
Ovarian Cancer - Sex cord stromal ovarian cancer
*Ovarian Cancer - Epithelial ovarian Cancer
Ovarian Cancer - Germ Cell Ovarian Cancer
*Pancreatic Cancer (Exocrine Cancers)
*Prostate Cancer
Others
*Sarcomas of the soft tissues
Skin cancers (excluding Melanoma)
*Stomach cancer
*Testicular cancer
*Thyroid
Small Lung cancer
In the study to determine the frequency of sick euthyroid syndrome (SES) among
patients diagnosed as non-small cell lung cancer (NSCLC) and its
association with the stage of the disease of enrolled 80 consecutive patients with newly diagnosed NSCLC, indicated that of out of 80 patients, sick euthyroid syndrome (SES) were identified in 28
(35%). SES was more frequent among stage III (26%) and stage IV (62%)
cases. The body mass index (BMI), KI and serum albumin level were
detected to be significantly low in cases with SES when compared to
cases without SES. SES was found to be negatively correlated with BMI,
KI and serum albumin level, and it was positively correlated with
disease stage. SES was frequently seen in cases with NSCLC. SES can be
used as a predictor of poor prognosis.
http://www.ncbi.nlm.nih.gov/pubmed/18701976http://www.ncbi.nlm.nih.gov/pubmed/18701976
Thyroid cancer
and Multiple myeloma
Heart failure
Heart failure (HF), or congestive heart failure, is defined as a condition as a result of damaged or
weakened by the diseases of the heart such as heart attacks. HF occurs when the heart is unable to provide sufficient pump action to maintain blood flow to meet the needs of the body, especially during increased
activity or under stress(a)(b).
A. Symptoms
1. Depression
Depression is common in patients with cardiac disease, especially in patients with
heart failure, and is associated with increased risk of adverse health outcomes(1).
2. Edema
There is a report of a case of 71-year old lady with a dual chamber demand pacemaker, who developed acute pulmonary
edema
due to an acute left ventricular (LV) dysfunction and worsening in
mitral valve regurgitation after atrioventricular nodal ablation for
uncontrolled atrial fibrillation(2).
3. Hyponatremia
In the review analyses the mechanisms relating
heart failure and hyponatremia, indicated that patients with
heart failure
often develop hyponatremia owing to the activation of many
neurohormonal systems leading to decrease of sodium levels. A large
number of clinical studies have associated hyponatremia with increased
morbidity and mortality in patients hospitalized for
heart failure or outpatients with chronic
heart failure(3).
4. Shortness of air
according to the study by the McGill University, certain health-related indices and environmental conditions affect self-reported health and
shortness of breath in CHF patients, although larger studies are needed to confirm these findings(4).
5. Fatigue
Fatigue is a prominent and poorly understood symptom of
heart failure with reduced ejection fraction (HFrEF)(5).
6. Irregular and Rapid heart beat
Patients with congestive
heart failure had significantly higher
beat-to-
beat QRS amplitude variability compared to controls in resting supine posture. This may partly be due to myocardial disease or
irregular respiration in this patient group(6).
7. Reduced ability to exercise
The minute ventilation-carbon dioxide production relationship VE/VCO2 slope, as an index of ventilatory response to
exercise,
is an excellent prognostic parameter and improves the risk
stratification of CHF patients. It is easier to obtain than parameters
of maximal
exercise capacity and is of equivalent prognostic importance than peak VO2(7).
8. Cough and night sweats and
Cough was more frequent in class I or II patients (28%) than in class III (4.1%, p<0.01) and class IV (0%, p<0.01) patients(8). Other study reported a case of 66-year-old woman with a history of myocardial infarction 2 months prior presented to our
respiratory
department with several days of dry cough and night sweats. Chest X-ray
and thoracic CT showed ground glass opacities or consolidation
spreading from the hilar area to the peripheral area, suggesting central
redistribution. Although neither rales nor abnormal
heart sounds were noted, she was tentatively diagnosed with congestive
heart failure based on those radiological findings(9).
9. Cardiac asthma
Cardiac asthma has been defined as
wheezing, coughing and orthopnea due to congestive
heart failureThe incidence of enalapril-induced
cough was evaluated in 199 patients with congestive
heart failure(10).
10. Abdominal complaints
Abdominal complaints are a common component of the presenting symptom
complex of CHF in pediatric dilated cardiomyopathy in all age groups. In
adolescents, abdominal complaints occur more frequently than
respiratory complaints and often in the absence of any other symptoms.
Unlike CHF in adults,
chest pain, arrhythmia, or cardiac arrest occurs
rarely at presentation in pediatric patients. Recognition of the
different presenting symptoms of
heart failure in children by primary providers is crucial to ensuring prompt diagnosis and timely initiation of therapy(11).
11. Constitutional symptoms
Constitutional symptoms such as
nausea,
lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing
heart attempts to maintain adequate function(12).
12. Cerebral hypoperfusion
Cerebral hypoperfusion such as dizziness, hearing difficulties, and vision problems including blurring, dimming, or a total “blackout." Cerebral hypoperfusion is common in
heart failure
(HF) and believed to underlie poor neurocognitive outcomes in this
population. Up to 42% of HF patients also exhibit depressive
symptomatology that may stem from reduced cerebral blood flow, according to the study by the Kent State University(13).
13. Elevated blood pressure
It is well established that
elevated blood pressure constitutes a major risk factor for coronary
heart disease, arrythmias,
heart failure, cerebrovascular disease, peripheral artery disease and renal
failure(14).
B. Causes and Risk Factors
B.1. Causes
Heart failure (HF), or congestive heart failure, is caused by damaged or
weakened by the diseases of the heart such as heart attacks.
1. Mitochondrial DNA
Heart failure
is a leading cause of morbidity and mortality in industrialized
countries. Although infection with microorganisms is not involved in the
development of
heart failure in most cases, inflammation has been implicated in the pathogenesis of
heart failure, according to the study by the Osaka University Graduate School of Medicine(15).
2.
B.2. Risk Factors
C. Complications and Diseases associated to heart failure
C.1. Complications
C.2. Diseases associated to Postoperative hypothyroidism
D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
D.2. Diagnosis
E. Prevention
F. Treatments
Anorexia nervosa
Sources
(a)
http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3484065/k.C530/Heart_disease__Heart_failure.htm
(b)
http://en.wikipedia.org/wiki/Heart_failure
(1)
http://www.ncbi.nlm.nih.gov/pubmed/22851113
(2)
http://www.ncbi.nlm.nih.gov/pubmed/24109499
(3)
http://www.ncbi.nlm.nih.gov/pubmed/24109495
(4)
http://www.ncbi.nlm.nih.gov/pubmed/19131052
(5)
http://www.ncbi.nlm.nih.gov/pubmed/22939040
(6)
http://www.ncbi.nlm.nih.gov/pubmed/17137652
(7)
http://www.ncbi.nlm.nih.gov/pubmed/20657715
(8)
http://www.ncbi.nlm.nih.gov/pubmed/18606471
(9)
http://www.ncbi.nlm.nih.gov/pubmed/24001730
(10)
http://www.ncbi.nlm.nih.gov/pubmed/23234454
(11)
http://www.ncbi.nlm.nih.gov/pubmed/23380118
(12)
http://www.ncbi.nlm.nih.gov/pubmed/22227365
(13)
http://www.ncbi.nlm.nih.gov/pubmed/24022882
(14)
http://www.ncbi.nlm.nih.gov/pubmed/24026758
(15)
http://www.ncbi.nlm.nih.gov/pubmed/22535248
hypothermia, myocardial infarction, chronic renal failure, cirrhosis,
and diabetic ketoacidosis and inflammatory bowel disease(c). inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, atherosclerosis, such as osteoprotegerin (OPG), are associated with elevated mortality, especially from cardiovascular diseases(d)
http://en.wikipedia.org/wiki/NF-%CE%BAB
http://www.jci.org/articles/view/7771
II.2. Hyperthyroidism
Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones.
A. Symptoms
B. Causes and Risk Factors
C. Complications and Diseases associated to Postoperative hypothyroidism
C.1. Complications
C.2. Diseases associated to Postoperative hypothyroidism
D. Misdiagnosis and Diagnosis
E. Prevention
F. Treatments
Thyroid stormGraves' disease
Toxic thyroid nodule
Toxic nodular struma (Plummer's disease)
Hashitoxicosis
III. Nodular abnormalities - Goitre
Endemic goitre
Diffuse goitre
Multinodular goitreLingual thyroid
Thyroglossal duct cyst
IV.
Deficiencies
Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones (congenital hypothyroidism) usually due to maternal hypothyroidism.
