All You Need To Know About Small Fibre Neuropathy

Today's post from ncbi.nlm.nih.gov (see link below) tells you all you need to know about small fibre neuropathy and how it's treated. It includes all the references because they are important to the relevance of all the facts and it's quite a read! However, if you've been diagnosed as having small fibre neuropathy, or suspect that your neuropathy may fall under that heading, it's worthwhile ploughing through it because you'll learn so much about what gives you so many problems in daily living. Small fibre sensory neuropathy (SFSN) is a disorder in which only the small sensory cutaneous nerves are affected and as such can be classified as being different to other forms of neuropathy but it's important to realise that the results are pretty much the same and that goes for the treaments too. It's so confusing for patients when they are confronted by so many terms describing their neuropathy. Here, we're talking about the small sensory nerves and other neuropathies apply to single nerves, or longer axons but whatever you've been given as a label, this post will apply to you in many ways. Worth a read but clear your head first! (n.b. the US spelling of fibre is 'fiber' - it's not a typo!)

Diagnosis and Treatment of Pain in Small Fiber Neuropathy
Alexandra Hovaguimian and Christopher H. Gibbons
Author information ► Copyright and License information ►
The publisher's final edited version of this article is available at Curr Pain Headache Rep
Abstract

Small fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting pain, allodynia, and hyperesthesia. Diagnosis of small fiber neuropathy is determined primarily by the history and physical exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve fiber density can provide diagnostic confirmation. Management of small fiber neuropathy depends on the underlying etiology with concurrent treatment of associated neuropathic pain. A variety of recent guidelines propose the use of antidepressants, anticonvulsants, opioids, topical therapies, and nonpharmacologic treatments as part of the overall management of neuropathic pain. Unfortunately, little data about the treatment of pain specifically in small fiber neuropathy exist because most studies combine mixed neuropathic pain syndromes in the analysis. Additional studies targeting the treatment of pain in small fiber neuropathy are needed to guide decision making.

Introduction

Peripheral neuropathy is an expanding public health problem, seen in nearly 40 million individuals in the United States [1]. Many of these individuals will have specific damage to small myelinated and unmyelinated nerve fibers, either in isolation or in combination with injury to larger myelinated nerve fibers. There are a variety of diseases that may result in a small fiber neuropathy, including diabetes and other glucose dysregulation syndromes (eg, impaired glucose tolerance and metabolic syndrome), thyroid dysfunction, sarcoidosis, vitamin B12 deficiency, HIV, neurotoxic medications (including many chemotherapeutic agents and antiretroviral agents), celiac disease, paraneoplastic syndromes, and paraproteinemias [2•]. Despite extensive diagnostic evaluation, up to 50% of individuals with small fiber neuropathy ultimately may be given a diagnosis of “idiopathic” [3•]. Regardless of the underlying etiology, pain is a common and often problematic feature of small fiber neuropathies. Therefore, therapy is tailored toward identification and treatment of the underlying cause of the neuropathy, when possible, while simultaneously managing symptoms of pain.

Definition of Small Fiber Neuropathy

A small fiber neuropathy occurs when damage to the peripheral nerves predominantly or entirely affects the small myelinated (Aδ) fibers or unmyelinated C fibers. The specific fiber types involved in this process include both small somatic and autonomic fibers. The sensory functions of these fibers include thermal perception and nociception. These fibers also are involved in a number of autonomic and enteric functions.

Most small fiber neuropathies occur in a length-dependent fashion, resulting in loss of function in a stocking distribution in the lower extremities. When the condition is more advanced, a glove-like loss in the upper extremities also may occur. In rare cases, a non–length dependent neuropathy results in symptoms involving the trunk, face, proximal limbs, or other focal areas [2•, 3•].

Anatomically, the small nerve fibers may be damaged or destroyed in these conditions, resulting in a loss of small nerve fibers and/or abnormal nerve fiber morphology. However, the pathogenesis of injury to small nerve fibers is not well understood. Small nerve fiber neuropathies can occur without large nerve fiber involvement, but in some cases they occur concomitantly or progress to involve large nerve fibers.

Symptoms of Small Fiber Neuropathy

Symptoms of small fiber neuropathy can vary widely in severity. Many individuals report the gradual onset of distal symptoms that include vague disturbances of sensation in the feet. These symptoms may include the feeling of a wrinkle in a sock that cannot be removed or of small pebbles or sand in the shoe. Others may report a cold-like pain, tingling or a pins and needles sensation. More severe symptoms of small fiber neuropathy may include burning pain that often is persistent, although it may vary in intensity throughout the day. Many patients also report transient electric shock–like pain, usually lasting only seconds, but quite severe and potentially multiple times per day. Many symptoms worsen during periods of rest and at night. In addition to spontaneous pain, many individuals report allodynia and hyperesthesia. Patients with small fiber neuropathy frequently complain that the bedsheets are exquisitely painful, and therefore, wear socks or use “foot tents” to keep the sheets from making physical contact with the feet.

Small nerve fiber neuropathies also may result in autonomic and enteric dysfunction. Patients often do not identify the relationship of these symptoms to their sensory complaints; however, when asked, they may report dry eyes, dry mouth, postural lightheadedness, presyncope, syncope, abnormal sweating, erectile dysfunction, nausea, vomiting, diarrhea, constipation, early satiety, difficulty with urinary frequency, nocturia, and/or voiding [4, 5].

Examination Findings in Small Fiber Neuropathy

One of the hallmarks of a pure small fiber neuropathy is a normal or near normal physical and neurologic examination. The coordination, motor, and reflex examinations will be normal. Light touch, vibratory sensation, and proprioception also may be normal, resulting in diagnostic confusion in some situations. Patients may have decreased pinprick, decreased thermal sensation, or hyperalgesia in the affected region. There may be mildly decreased vibratory sensation in some individuals. Associated skin changes in affected areas may include dry, cracked, or shiny skin, with decreased moisture on the surface of these affected areas as well.

Causes of Small Fiber Neuropathy

Diabetes and prediabetes (including both impaired glucose tolerance and impaired fasting glucose) frequently are associated with pure small fiber neuropathy; however, concomitant large fiber involvement is seen more often [6]. Nearly half of all subjects with idiopathic small fiber neuropathy have abnormal 2-hour glucose tolerance tests or abnormal fasting glucose levels [6, 7]. The abnormal glucose testing may be seen despite normal glycosylated hemoglobin. Several studies have also established a link between pain in small fiber neuropathy and abnormal glucose metabolism [8, 9]. There also is a large overlap between prediabetes and metabolic syndrome. The metabolic syndrome is comprised of hyperlipidemia, hypertension, and obesity in addition to abnormal glucose metabolism with insulin resistance. Each of these separate factors appears to convey an increased risk of developing a small fiber neuropathy [10]. Individuals with diabetes and metabolic syndrome appear to have twice the risk of developing a small fiber neuropathy compared to those with diabetes alone [11]. Recent reports now are suggesting that the single largest contributing factor to neuropathy development is hyperlipidemia [12•, 13••]. Some patients with diabetes also may experience an acute painful small fiber neuropathy associated with rapid glycemic control, also referred to as insulin neuritis or treatment-induced neuropathy [14•].

Other conditions associated with acquired small fiber neuropathy include HIV [15, 16], inflammatory neuropathies (such as Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy) [17, 18], celiac disease [19, 20], hepatitis C [21], restless legs syndrome [22], complex regional pain syndrome type I [23], paraproteinemia [24], neurotoxic drug use [25–27], systemic lupus erythematosus [28], Sjogren’s syndrome [29], abnormal thyroid function [2•], amyloidosis, and paraneoplastic syndromes [30, 31]. This list is not comprehensive and there are many case reports describing small fiber neuropathies in other diseases. In addition, there are inherited conditions which cause small fiber neuropathies, such as Fabry’s disease and the hereditary sensory and autonomic neuropathies.

Diagnosis of Small Fiber Neuropathy

The history and physical examination findings still are considered the gold standard against which all tests are compared when making a diagnosis of a small fiber neuropathy. A detailed review of the symptoms, rate of progression, and complaints suggestive of autonomic fiber involvement is necessary. Generally, if a patient presents with a compelling history for a small fiber neuropathy and an appropriate clinical exam, further testing to confirm the diagnosis may be unnecessary. This scenario is particularly likely in the context of an associated disease, such as diabetes. However, in many cases, the diagnosis may be less clear and ancillary testing may provide additional guidance. Patients should always be screened for other treatable causes of small fiber neuropathy. Recently, scoring examinations have been developed, and may aid in diagnosis of small fiber neuropathies [32•]. In addition, the specific types of pain experienced by patients with small fiber neuropathy may need to be characterized. The Neuropathic Pain Symptom Inventory differentiates various aspects of neuropathic pain, and may aid in selection of treatments as clinical trials begin to select specific aspect of neuropathic pain as targets [33].

Quantitative Sensory Testing

Quantitative sensory testing (QST) is an extension of the physical examination that can provide a threshold for detection of thermal sensation, thermal pain, and vibratory sensation. QST has been used in a number of longitudinal studies and clinical trials of neuropathy and is widely available [34]. There are some well-recognized limitations to QST; abnormalities in either the central or peripheral nervous system can result in the same deficit. In addition, QST requires conscious integration from the patient, and in conditions of cognitive impairment (due to disease or medication), the reliability of the test results are in question. Finally, QST is unable to distinguish between feigned and true loss of sensation [35].

There are few trials utilizing QST in the study of isolated small fiber neuropathies, most trials include patients with large fiber involvement as well [34, 36]. Heat or heat-pain detection thresholds are considered the most useful and specific for evaluation of a small fiber neuropathy. Cold and cold-pain detection are transmitted through lightly myelinated Aδ fibers, while vibration detection thresholds are detected through large myelinated Aα and Aβ sensory fibers. Recent reports of contact heat evoked potentials (CHEPs), a device that provides rapid cycles of heat resulting in evoked potentials measured by electroencephalogram, show a linear correlation between CHEP amplitude and cutaneous nociceptive nerve fiber density [37]. Further study is required to determine the utility of new variations of QST on the diagnosis of a small fiber neuropathy.

Quantitative Sudomotor Axon Reflex Testing

There are a variety of methods to quantify sudomotor function. The most frequently utilized and well-known test is quantitative sudomotor axon reflex testing (QSART), a measure of postganglionic sympathetic cholinergic function. Local sweating is produced through iontophoresis of acetylcholine; this method uses a mild electrical current to draw acetylcholine (a charged substance) into the skin, causing activation of local sweat glands. The stimulation also triggers an axon reflex resulting in neighboring sweat glands, not stimulated by acetylcholine, to produce sweat. The axon reflex–mediated sweat output is detected by passing dry gas over the nonstimulated region and quantifying the change in humidity of the gas. A study of patients with small fiber neuropathy revealed that QSART was abnormal in 74% of patients, and that sudomotor dysfunction may be the earliest manifestation of a distal small fiber neuropathy [38]. Another study reported QSART to be abnormal in 73% of patients with painful feet from a small fiber neuropathy. A variety of other tests, including sweat imprint tests, thermoregulatory sweat testing, and quantitative direct and indirect sudomotor testing, also detect abnormalities in patients with a small fiber neuropathy. To date, no prospective controlled study has evaluated the ability of these tests to diagnose a small fiber neuropathy.

Skin Biopsy

Skin biopsy has become a widely accepted technique to investigate the structural integrity of small nerve fibers [39]. A standard 3-mm dermatologic punch biopsy can be taken from any location on the body, but typically is performed on sites of interest in evaluation of a distal small fiber neuropathy (the lateral distal leg, the lateral distal thigh, and the lateral proximal thigh to look for a length-dependent pattern). For clinical investigation, bright field immunohistochemistry is used with antibodies against protein gene product 9.5, a marker for all peripheral nerve fibers. The number of fibers crossing the dermal/epidermal junction is quantified through standardized means, and results are expressed as the number of intraepidermal nerve fibers per millimeter. Recently revised consensus statements have highlighted the utility of skin biopsy in the evaluation of small fiber neuropathy [40•]. The sensitivity (78%–92%) and specificity (65%–90%) of skin biopsy for diagnosing a small fiber neuropathy is fairly high across all studies. In early or mild cases of small fiber neuropathy, morphologic abnormalities of nerve fibers may aid in diagnosis if nerve fiber density is not reduced [41]. Unfortunately, there are no data on the utility of skin biopsy to diagnose the etiology of the small fiber neuropathy.

Electromyography and Nerve-conduction Studies

Electromyography and nerve-conduction studies are well-established neurophysiologic techniques used to assess the integrity of larger myelinated sensory and motor fibers. These studies often are normal in pure small fiber neuropathies. If there is question of possible larger fiber involvement causing symptoms or occurring concomitantly with a small fiber neuropathy, these studies can clarify if larger sensory and/or motor nerve fibers are involved.

Treatment of Pain in Small Fiber Neuropathy

Treatment of any underlying causative etiology of a small fiber neuropathy is likely to be the most effective treatment of pain, when possible. Many cases of small fiber neuropathy will remain idiopathic, or will still require treatment of pain. There is very limited evidence for specific medications in the treatment of pain from small fiber neuropathies. Most clinical studies have examined drugs in the treatment of many neuropathic pain syndromes (such as postherpetic neuralgia and painful diabetic neuropathy). In some trials, the spectrum of neuropathic pain can be broad and include diagnoses such as central neuropathic pain, radiculopathy, or carpal tunnel syndrome. These disorders may respond to treatment differently than pain from small fiber neuropathy. This is a challenge when developing treatment recommendations for small nerve fiber pain because comparative effectiveness across different pain states is not known.

This issue is further complicated by evidence suggesting that some diseases causing neuropathic pain respond differently to the same medications. Neither HIV nor chemotherapy-related neuropathic pain respond to treatments that are effective for other forms of neuropathic pain. It is unclear if these discrepancies are methodological or due to differences in the underlying disease state. In addition, head-to-head trials of medications and long-term outcome data for small fiber neuropathies are lacking. When possible, disease-specific treatment guidelines should be selected for management of pain in small fiber neuropathy (eg, diabetes, HIV, or chemotherapy).

In patients with idiopathic small nerve fiber neuropathy pain physicians must select treatments based on evidence of safety, efficacy in other neuropathic conditions, tolerability, drug interactions, comorbid conditions, and cost [42]. There are a number of recent consensus guidelines for the treatment of neuropathic pain [43, 44, 45•, 46, 47 48••]. None of the guidelines specifically examine treatment of pain secondary to small fiber neuropathy. Several provide recommendations based on patterns of pain or underlying disease. Most of these guidelines are based on reviews of available randomized clinical trials published in MEDLINE and the Cochrane database, although some used additional resources. The criteria used to establish the guidelines varied somewhat, although all used randomized control trials. Other variables such as safety, efficacy, tolerability, number needed to treat (NNT), side-effect profile, comorbid conditions, effect on quality of life, cost and, ease of use also were considered. Certain guidelines also addressed population-specific issues such as availability and genetic features. These guidelines were published between 2006 and 2010; the older publications do not include the most recent trials. There is significant agreement about medications among these recommendations, although classifications of first-, second-, and third-line agents vary. Table 1 highlights the recommendations of these recent guidelines and consensus statements [43, 44, 45•, 46, 48••].



Table 1

Summary of Guidelines

There are several different classes of medications commonly used to treat neuropathic pain. These include antidepressants, anticonvulsants, opioids, and topical treatments. Tricyclic antidepressants (TCAs) consistently are recommended as first tier drugs across all guidelines [43, 44, 45•, 46–48]. The criterion for study inclusion varies amongst the guidelines; however, the number of studies for neuropathic pain reviewed ranged from 2 to 17. The NNT was 2.1 to 2.5 based on the type of TCA. None of the studies specifically treated patients with small fiber neuropathy. TCAs consistently were selected as first-tier choices based on their efficacy and other factors such as cost and availability. Their mechanism of action is inhibition of serotonin and norepinephrine reuptake. TCAs also have anticholinergic effects that can cause significant side effects for some patients, and specifically should be avoided in elderly adults. They are contraindicated in patients with a significant cardiac history, glaucoma, or recent monoamine oxidase–inhibitor (MAOI) use. Guidelines note that safety and tolerability factors may limit the use of TCAs.

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are another class of antidepressants commonly used for the treatment of neuropathic pain. Both duloxetine and venlafaxine are recommended as second-line agents in most guidelines. For duloxetine, most guidelines reviewed two to three studies [43, 44, 45•, 46, 47, 48••]. It has been found to be effective in painful diabetic neuropathy and the NNT was 5.2. It has not been studied for other forms of neuropathic pain; therefore, it is frequently recommended as second- or third-line treatment. It has a rapid onset of action and is generally well tolerated. It should be avoided in patients with uncontrolled narrow-angle glaucoma or those being treated with MAOIs. In rare cases it has been associated with abnormal bleeding, hepatotoxicity, and serotonin syndrome.

Venlafaxine is another SNRI that typically is recommended as a second-line agent. Two studies have found it to be effective for painful diabetic neuropathy and for mixed neuropathy with a NNT of 4.6 [43, 44, 45•, 46, 47, 48•]. In a study that compared imipramine and venlafaxine head to head, the imipramine group had a higher proportion of responders [49]. Generally, venlafaxine is well tolerated, but should be avoided in patients being treated with MAOIs. In some cases, it has been noted to increase blood pressure and cause ECG changes. Rare adverse events including bleeding, hyperlipidemia, and pulmonary complications (interstitial lung disease and eosinophilic pneumonia) have been reported. Due to differences in the NNT, TCAs are recommended over SNRIs in most guidelines except in elderly patients or others at risk for adverse events.

In addition to antidepressants, anticonvulsants also are routinely recommended for the treatment of neuropathic pain. Gabapentin frequently is utilized as a first-line treatment of neuropathic pain. Most guidelines reviewed two to four studies and the NNT was 3.9 to 4 [43, 44, 45•, 46, 47, 48••]. It is effective for neuropathic pain (specifically postherpetic neuralgia and painful diabetic neuropathy). The mechanism of action is believed to be via the voltage-gated α2δ calcium channel, modifying the release of excitatory neurotransmitters. It is well tolerated and not known to cause significant drug–drug interactions. In rare circumstances, it has been associated with Stevens-Johnson syndrome.

Pregabalin is another anticonvulsant frequently used for first-line treatment of neuropathic pain. In the included guidelines, two to six studies on pregabalin in different types of neuropathic pain (postherpetic neuralgia, painful diabetic neuropathy, or both) were reviewed. For some guidelines, several studies were excluded based on concern that the methodology included enriched enrollment. The calculated NNT was 4.2 [43, 44, 45•, 46, 47, 48••]. Pregabalin’s mechanism of action also is believed to be through the voltage-gated α2δ calcium channels and is a presynaptic inhibitor of the release of glutamate, substance P, and calcitonin gene–related peptide (CGRP). It also is typically well tolerated, but should be used with caution in patients with congestive heart failure. Angioedema rarely has been described as a side effect.

Topical lidocaine frequently is recommended as a first- or second-line treatment of focal neuropathic pain. These recommendations are typically for the lidocaine patch, although there also is evidence available for lidocaine gel. The guidelines included three or four studies (primarily for postherpetic neuralgia) and the NNT is 4.4 [43,44, 45•, 46, 47, 48••]. It is generally most effective for patients with focal regions of pain and offers the advantage of less systemic side effects and drug interactions. It also may be used for breakthrough pain. It is believed to act by decreasing neuronal membrane permeability to sodium ions. Topical lidocaine is more expensive than some of the other treatments, but is generally well tolerated. It should be avoided in regions of skin breakdown. Rare allergic or anaphylactic reactions can occur.

Lastly, opioids and tramadol frequently are recommended as second- or third-line medications across all guidelines. Among expert opinions, there is consistent concern about the use of opioids for nonterminal neuropathic pain due to dependence. Some guidelines review different types of opioids (oxycodone, morphine, methadone, and levorphanol) as well as different types of neuropathic pain (painful polyneuropathy and post-herpetic neuralgia). The number of studies included ranged from five to eight and the NNT ranged from 2.5 to 2.7 based on the type of neuropathic pain and the drug [43, 44, 45•, 46, 47, 48••]. Some guidelines suggest that opioids, typically oxycodone, be used for severe breakthrough pain either for acute exacerbations or during titration of another agent. While effective for pain, opioids pose the potential for many side effects as well as overdosing and dependence.

Tramadol is consistently recommended as a second- or third-line choice for treatment of neuropathic pain. Concerns for dependence also are raised with tramadol use. The number of reviewed studies ranged from two to three among the guidelines and included painful diabetic neuropathy, mixed polyneuropathy, or postherpetic neuralgia. The NNT ranged from 3.4 to 4.8 based on the type of neuropathic pain and criteria applied [43, 44, 45•, 46, 47, 48••]. Tramadol and its active metabolite bind to central μ-opiate receptors and inhibit ascending pain pathways. Tramadol also causes serotonin and norepinephrine–reuptake inhibition, another potential mechanism of pain relief. Side effects of tramadol can include dyspnea and respiratory depression, and it is rarely associated with myocardial infarction, pancreatitis, seizure, and serotonin syndrome. It should be avoided in patients who are actively using central nervous system depressants such as alcohol, hypnotics, opioids, or psychotropic drugs. In addition, tramadol does have the potential to interact with most antidepressant medications, and care is required due to the potential duplicative serotonin- and norepinephrine-reuptake inhibition. Also, up to 10% of Caucasians are poor cytochrome P450 2D6 metabolizers and, therefore, are unable to metabolize the drug effectively, resulting in poor efficacy [50].

In the only published study specifically examining treatment of small fiber neuropathy, both gabapentin and tramadol were found to be effective [51]. This study used an enrichment crossover design. Participants were included if they had biopsy-proven small fiber neuropathy and were self-identified as gabapentin responders. Patients first were treated with single-blinded gabapentin at their prestudy dose as well as matching diphenhydramine placebo, 50 mg, capsules for 1 week. Participants with a pain intensity score of 7.5 or higher were then allowed to continue to the second phase, in which patients were tapered off their gabapentin dose during the first week and continued on the diphenhydramine placebo for 2 weeks. Pain scores were assessed during the second week, and those participants with a pain score of 3 or higher and a 30% or greater increase from their initial phase pain scores then were randomized into a double-blind crossover phase. During the last phase of the trial, patients were randomized to three 2-week double-blind treatment periods with1-week washout periods between each treatment phase. Overall, 18 participants were treated in a randomized crossover design with 3 treatments: gabapentin at their prestudy dose, tramadol, 50 mg four times daily, and diphenhydramine 50 mg at bedtime. Three participants withdrew before completing all three treatment periods. There was a statistically significant improvement in pain scores for both gabapentin and tramadol groups when compared to diphenhydramine. The NNT for gabapentin was 4.6. The NNT for tramadol was 4.0. There was no statistically significant difference between the average pain scores during the gabapentin and tramadol treatment phases. There were no reported significant adverse events in either treatment group.

Other classes of medications have been used for the treatment of neuropathic pain including antiarrhythmics. This class typically is excluded from expert panel recommendations due to the large number of potential side effects. Selective serotonin reuptake inhibitors also are excluded as first- or second-line recommendations due to limited data on efficacy. For detailed descriptions of the guidelines, included studies, drugs and dosing, please refer to the recently published guidelines for neuropathic pain listed in Table 1 [43, 44, 45•, 46, 47, 48••].

Nonpharmacologic options also are important for pain management. Some patients may benefit from cool or warm soaks, soft socks, and foot tents. Other treatments such as transcutaneous electrical nerve stimulation, acupuncture, physical therapy and massage also have been used, but have not been examined in clinical trials for small fiber neuropathic pain [43, 44, 45•, 46, 47, 48••].

Conclusions

Small fiber neuropathy frequently is associated with neuropathic pain. The clinical history and physical examination often are sufficient to make the diagnosis of a small fiber neuropathy; however, additional functional and pathological tests may help to confirm the diagnosis. Patients should be carefully screened for reversible causes of small fiber neuropathy. A variety of medications for treatment of pain exist, and there are a number of available consensus guidelines that can aid clinicians in selecting appropriate treatments. For some conditions, such as painful diabetic neuropathy, there are additional treatment guidelines available. However, additional studies specifically targeting the pain in small fiber neuropathy are necessary to support clinical decision making. With the advent of new medications coming to market, further review of the literature will be necessary.

Acknowledgement

This work was supported in part by a grant from the National Institutes of Health (NINDS K23 NS050209 [CHG]).

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086960/

All about urine

All about urine

URINARY SYSTEMS – All about urine

Water is essential for survival of life. The water we take washes and

cleans our body and comes out as urine. Water usually is lost from our body through skin, lungs faeces and urine. Our body’s outer surface is kept clean by bathing with water and cleaning of inner organs and tissues are done by blood plasma by the process of osmosis or electrolyte transportation between tissues with our water intake. This blood plasma is filtered by kidneys and liver and kept clean and perfect. The waste product thus filtered out by the kidneys is urine.

Drinking water and pissing (process of urination) is inevitable for every animal or human being. There is a saying that “we can well control our bouts of anger, but not the urine”. Everyone might have experienced the pleasure of passing urine after controlling it for a long time. Children do pissing as an art. A newborn has to urinate within 12 hours of the birth time or otherwise it should be seriously investigated. Urination is so much important for our body to maintain it clean and make it non-toxic. The digestive tract or stool habit can go on strike (without passing stool) for days, sometimes even for a week, but our kidneys cannot take rest even for a single day.

Urine can indicate 
1. Urinary tract infection with lab analysis

2. Systemic illness with increased frequency and volume of the urine, such as renal excretory disorders, hypertension (in initial stage, by natural process, urination frequency and volume of urine is increased, so automatically blood volume as well as blood pressure gets lowered), anaemia,etc.

3. Metabolic disorders with increased frequency and volume of the urine with glucose (diabetes), increased elimination of fructose (fructosuria), uricosuria (gout), etc.

4. Pregnancy in women. It can also show adulteration in foods (food colours, presence of toxic substances, etc.), chemicals in water, etc. when analysed in a lab

5. It can also show the culprit or cheat who takes steroids in sports. Likewise, it can also help to identify persons who have ingested alcohol or drugs

Urine often cautions one about a disease in the early stages itself. If we do not take care, the disease will get rooted and expand leading to damage of the inner organs. Nowadays, everyone hears about old people or devotees or leaders or their followers or diseased people drinking their own urine to stay healthy or cure their problems. Is it needed for cleaning the bowels, as said by urine therapists? Does urine contain active ingredients or has medicinal values? What is urine? How it is formed? Why does it get eliminated? Does disease get reflected in urine? What are all the diseases or conditions that get reflected in urine? What is to be noted during urination? Someone complains about yellowish urine and someone else about hot urine. Does this denote body heat or is there any inference from it? How to test it? Why is urine analysed in a lab? We shall analyse these questions one by one.

What is urine? Urine is a body’s eliminating fluid which is supposed to be a waste product. It usually contains waste or excess materials from our body, toxic substances, etc. Its main constituent is water.

Normal composition of urine is water – 95 per cent, other major and common constituents are sodium – 0.4 per cent, ammonia – 0.05 per cent, phosphates – 0.6 per cent, urea – 2 percent, sulfate – 0.2 per cent and creatine, urobilinogen, casts, etc. in minute quantities. Normally, soluble substances are excreted in the urine.

How it is formed?
Urine is produced by the kidneys as a process of cleaning the blood and excreting the unwanted soluble waste products from the body. Millions of nephrons in the kidney filter out the waste products, toxins, excess water and mineral salts from the bloodstream. Kidney, the leader of water balance mechanism, eliminates nitrogenous wastes in a non-toxic concentrated form. To maintain fluid balance, it filters, cleans and purifies about 150-180 litres of blood and recycles it daily. The urine formed in the kidney is drained by ureter into the bladder for storage. The urethra brings out the urine from the bladder, when time and place permit. Urination is normally controlled by a reflex phenomenon with urinary sphincters.

Since kidneys work as an eliminator and absorber with their permeability, they can also control the blood volume by adjusting urine volume to control blood pressure naturally. When there is dehydration, it reabsorbs the water from distal tubules and balances the blood volume. In case of hypertension or excess fluid intake, it eliminates the water and reduces blood volume and blood pressure. So, till the urine gets into the bladder from the kidney, it has control over urine in every aspect. The kidneys maintain blood acidity by excreting excessive alkaline salts for controlling infection in the blood. The action of the kidney is mainly controlled by endocrinal glands.

Why does it get eliminated?
Urine is eliminated because it is considered a waste product or an excess product. So, nature cares for its elimination, to avoid overdose or toxicity and compels the kidney to do the elimination process i.e. elimination of urine. In order to maintain blood acidity, excess alkaline salts are filtered in the kidney. The filtered product should be excreted anyway, so with the vehicle of water medium these salts are excreted in the urine.

Is it needed for cleaning the bowels, as said by urine therapists?
No, it is not necessary. The water we take is enough for the business in the bowels.

Does urine contain active ingredients or has any medicinal value?
No. Nothing has been proved like that till now. Since urine is decided as an unnecessary waste product by nature or the body, it gets eliminated from the body by or as natural process, so we do not need to recycle it for any purpose.

People who follow urine therapy mainly claim by quoting that the amniotic fluid that surrounds babies in the womb is supposed to be primarily the urine of the embryo which has quick healing effects on abrasions or bruises or cuts or any lesion, like sea water.
Till now, with active research, no medicinal value is evaluated as such.

Do diseases get reflected in urine?
Yes, most of the diseases in the initial or final period reflect their nature in colour, volume, sp gravity and contents of the urine. Most of the diseases of the bladder or urinary tract are often faced by women than men since the male urethra is 6-8 inches long whereas the female urethra is only 1½ inches long. So any infection can easily enter into the bladder and ascend to the kidney to disturb the urine and its constituents. Also the urethra of women is very close to the vagina, so any infection of one can spread to the other.

Diseases often reflect their occurrence or presence with the following symptoms or problems:

• Dark, scanty and strong smelling urine – in case of infection (cystitis- infection of the bladder, nephritis – infection of the kidney, urethritis – infection of the urethra, ureteritis – infection of ureter, etc.)
• Burning urination, difficulty in urination and painful urination – infection and obstruction
• Reduced volume (oliguria) – infection, obstruction, renal stones, kidney failure, etc.
• Increased volume of urine (polyuria) – hypertension, diabetes, nephrotic syndrome, intake of beer or alcohol or drugs, endocrinal disorders
• Absence of urine (anuria) – obstruction or kidney failure or stenosis
• Sweetish smell of urine or sugar in the urine (glycosuria) – diabetes, kidney damage due to drugs, toxins, etc.
• Offensive urine or proteins in the urine (proteinuria) – diabetes, kidney damage due to drugs, toxins, etc.
• Bloody urine (haematuria) – infection or renal stones
• Yellowish urine with bilirubin in the urine – liver disorder – jaundice, cirrhosis, etc.
• Semen in urine with great exhaustion (semonorrhoea) – prostate problems
• Backache early in the morning – infection, renal stones (due to fullness of kidney, pelvis)
• Urinary tract infection with Leucorrhoea in females – due to spread of infection into the urinary tract (honeymoon cystitis occurs in newly-married females due to overindulgence in sex)
• Fatigue and exhaustion – Renal problems when excreting needed constituent in urine
• Lower abdominal pain or supra pubic pain – due to infection or stones

What are the diseases or conditions that get reflected in urine?
Diabetes, hypertension, metabolic disorders, renal disorders, liver disorders, jaundice, urinary tract infection, high fever, etc., can reflect their presence in urine. Nervous disorders like paralysis, paraplegia, cerebral lesion & cerebellar lesion can hinder bladder emptying capacity and reflect in stagnation and infection. Conditions like increased sweat, summer, air-conditioned room, heavy exercises can also reflect in urine in its concentration and volume.

What is to be noted during urination?
Force, flow, frequency, control, volume, pain, colour, odour and gravels or deposits.

Force, flow, frequency and control of urine – Always talk to a doctor and get the urine analysed, if there is any intermittent flow, uncontrolled urine, difficulty in starting the urine stream, spraying of urine during urination, lack of a force in stream of urination, dribbling urination, slow thin stream of urination, etc. The common problems affecting force and flow of the urine are urinary tract infection, urinary obstruction, urethral stricture, phimosis, renal stone, congenital abnormalities like narrow urethral opening (meatal stenosis), etc.

Frequency of the urine is often found when there is increased intake of water or in diseased condition like diabetes, hypertension, etc. Small bladder and urinary tract infection can also cause frequency of the urine due to early fullness or irritability due to infection and a disability to hold the urine for a long time. Here also, there won’t be any satisfaction after passing the urine since the weak bladder cannot constrict fully to empty the urine. The stagnated urine further irritates the bladder and produces the impulse for urination and makes the person go to the toilet often. Urinary incontinence or uncontrollability can be seen in nervous affections like paralysis or paraplegia or autism or cerebral lesion or cerebellar lesion or spinal injury causing damage to spinal nerves. To treat these types of ailments, the complaints should be evaluated in a detailed manner to attain diagnosis and treatment. Anxiety and tension in mind also causes frequent urination due to increased blood circulation.

Normal volume of urine excreted is 800 ml – 2200 ml/24 hrs. It varies with the intake of the water or fluids. Urine volume normally reflects the organism hydration state. It is according to body activity or exercise, but usually ¾ th of the ingested liquid should be excreted as urine. It is mostly regulated by ADH (anti diuretic hormone). The increased amount of water intake will induce increased excretion of urine (polyuria). In case of increased water intake and increased urine elimination, the excreted urine will be very much diluted or has low concentration of solutes. In a dehydrated state or during diarrhoea or vomiting, the anti-diuretic hormone gets increased in circulation and increases the permeability of the renal collecting tibule epithelium, so that maximum amount of water is re-absorbed. Hence, urine formed in this occasion will be scanty and very much concentrated with solutes.

The volume of urine usually increases in case of increased fluid intake, diabetes, hypertension (BP) and decreased in case of reduced fluid intake, low blood pressure, nephritis, fever, diarrhoea, vomiting, shock, burns, etc. The volume of the urine mainly depends on the presence of sodium, which in turn depends on aldosterone – a mineralocorticoid hormone secreted by the adrenal glands. Sodium holds water in plasma itself, so only in case of odema or hypertension doctors often advise reduced salt intake.

Colour – It is normally pale yellow or amber or clear depending upon a person’s health, water intake and diet. Even an uneducated man would get suspicious if there is any change in colour of the urine. Change in colour is mainly due to bilirubin. It may also change due to drugs, colours, dyes and chemicals used in sweets, foods, etc.

• Yellowish urine indicates presence of bilirubin (jaundice) or excess of vitamin-B
• Cloudy turbid urine always denotes infection and loads of bacteria
• Smoky urine indicates the presence of blood cells or any other chemicals
• Red or brown urine indicates the presence of blood (renal stones, infection, etc.)
• Whitish urine indicates the presence of phosphate of lime

Frothy urine is often passed in case of jaundice or renal damage. It indicates the presence of bile salts or albumin.

Odour – Urine mostly has the odour of ammonia, due to the nitrogenous wastes present in the urine. Aromatic foods can also affect the odour (large amount of asparagus intake can cause a putrid odour during urination). Urine may smell like sweet or fruit in case of diabetes and large amount of ketone bodies excretion. Usually, adult urine is smellier than children’s since adults take a higher protein diet. The bacteria present in the urine usually reduce nitrate to nitrite with the presence of ammonia in the urine. This gives it the smell. Normally, this bacterial action needs 4-5 hours to occur. So, morning urine or concentrated and stagnated urine is smellier than normal, frequently passed, diluted urine.

Gravels or deposits – are minute sediment particles present in the urine. They are noticed when the urine is much concentrated and are seen at the bottom of the sample or found like sand in the urine. They can be viewed easily after getting centrifuged in the lab. They are supposed to be coagulated protein casts, cell debris, RBCs, WBCs, bacteria, pus cells, tiny stone gravels, etc.

Somebody may often complain about yellowish urine and some others about very hot urine. What is the inference?

Actually, yellowish urine denotes its concentration. It is always seen in cases of scanty urine, especially after heavy exercises or long distance travel or sunbath. Urine is scanty and concentrated due to an alternative pathway of water elimination, i.e., through sweat, to maintain the thermostat of the body. If sweat is more, then urine will be concentrated more due to less availability of water to carry solutes. If water intake is increased, the concentration automatically gets diluted and the colour will resume to normal. But if you find yellowish urine even after plenty of water intake, it is better to rule out jaundice.

Usually, morning urine is more concentrated than at other times since we do not drinking water at night. So, to maintain the water balance of our body, less water is excreted and thus the urine becomes more concentrated.

Hot urine is a reflection of the body’s internal temperature, i.e., it is felt more during the cold weather (where the body maintains internal temperature as warm as it can) or after violent exercises (where the body temperature is high due to increased body metabolism).

How to test urine?
By urinalysis

What for it should be analysed in the lab?
Urine tests are simplest, painless, cheapest, non-invasive and highly informative, which can guide treatment. In all urinalysis, normal value varies with age, sex, time, device used, solvents or kit used, analyser, sample collecting techniques (after fasting, before fasting, etc.), etc.

Even though urinalysis is mostly done in case of a urinary tract infection and renal complaints, it is necessary to do in all cases of prolonged complaints or diseases, to rule out any systemic complication. Also, it should be made part and parcel of routine periodic health examination to analyse our body condition.

How should urine be analysed?
For analysis, urine samples must be collected in a proper way, i.e. care must be taken in collecting the sample in a clean, fresh, sterilised bottle or container without any contamination. The best urine sample is midstream of first (morning) urine.

Most of the laboratories are now doing urine test and blood test with automated analyser which gives report in printed colour strip form. They measure everything electronically.

Investigations
Microscopic examination – urine should always be evaluated microscopically for the presence of casts, crystals, cells and bacteria.

Lab or chemical analysis of urine – is done for evaluating pH, specific gravity, sugar, albumin, ketone bodies, bile salts, pigments, blood, etc.

pH – (hydrogen ion concentration which helps in denoting acidity or alkalinity of the solution variation from 1-14 i.e. from most acid to most alkali). Urine is usually slightly acidic i.e. below 7 (indicated by blue litmus paper turning red on getting dipped) but normal range is between 5.5- 8.0. Occasionally, it becomes alkali (red litmus paper turns blue) during infection where pH is raised.
pH of urine in case of child – 6.2 – 6.8
pH of urine in case of adult – 5.2- 8.0

Specific gravity of the urine changes according to the volume of the urine and solute present in the urine. In case of reduced volume of the urine in normal excreting solutes, the sp gravity is raised; whereas in increased volume of urine with normal excreting solutes, it is lowered. Increased level of protein in the urine also elevates the sp gravity.

Humans are soft-skinned persons who sweat more to produce more hypertonic (highly concentrated) urine. Insects, spiders, reptiles, birds and other animals excrete less hypertonic urine since they have hard body protective surface or hair or feathers which usually protect loss of fluids from sweat. Fish and other water animals always pass hypotonic (less density) urine. Also, humans take a good amount of sodium salt in diet which will hold or retain water content in the body. The distal renal tibules in humans are also designed in such a way to reabsorb most of the water and salts to maintain our body water balance which causes urine to be more hypertonic.
Specific gravity normally ranges from – 1.001 – 1.035
Normal sp gravity of urine in children – 1.002
Normal sp gravity of urine in adult – 1.030

Sugar or glucose in urine – Glucose is always absorbed more

rapidly than water. If there is excess glucose in the blood due to lack of insulin (which is essential for glucose metabolism in the body) or when there is kidney damage due to drugs or toxins, glucose can occur in urine (glycosuria). In this case, urine test for glucose should be done in 12 hours fasting time and also, after two hours of food intake (post prandial) to analyse it thoroughly. The presence of sugar is now analysed by two methods, i.e., one by old Benedict’s reagents and another by latest dipsticks. In case of Benedict’s test, if results shows
Blue colour – Nil
Green colour – + (0.1- 0.5 g/dl)
Yellow colour – ++ (0.5- 1.0 g/dl)
Orange colour – +++ (1.0- 1.5 g/dl)
Brick red colour – ++++ (1.5- 2.0 g/dl)

Protein in urine (proteinuria) – Acceptable normal excretion range of protein in urine is below 0.15 gms/24 hours of urine. This occurs usually due to day-to-day activities or exercises where protein metabolism is used for energy. Proteins occur in urine in diseases like kidney disorders (nephrotic syndrome, renal failure, pyelonephritis, etc.) heart failure, gout, malignant hypertension, toxicity of high fever, drugs, eclampsia (convulsive disease due to high BP and proteinuria in pregnant women), etc. They usually appear as casts in urine, which can be confirmed by their coagulation or white precipitation while heating.

Albumin – Normal range of albumin in urine is <3.5mg/mmol. Test for Microalbuminuria (increased elimination of albumin) is most important test to be done in diabetic patients to rule out kidney involvement or damage. Since albumin level varies with day-to-day activities and exercises, it is better to test after overnight rest. It is often traced in cases of heart failure, renal failure, hypertension, urinary tract infection, etc.

Urea – is the end product of protein metabolism. A high protein diet will increase urea level (normal 20-40 mg /100ml) in blood and urine. It will be abnormally high in cases of kidney disorders (where there is defect in filtration and elimination) and diabetes (due to use of protein metabolism for energy since glucose metabolism is impaired). Normal acceptable range of urea in urine is 180-600mmol/24 hours.

Ketone bodies (Acetone) – normal level in urine is <500mg/24 hours – starvation and uncontrolled diabetes can elevate the levels.

Bile salts and bile pigments – give yellow colour to urine when they occur during jaundice

Urobilinogen – is excreted in increased amount in case of liver disorders.

Other normal levels
Sodium – 100 -200mmol / 24 hours
Potassium – 25 – 100mmol / 24 hours
Calcium level – 0 – 300 mg / 24 hours
Phosphates – 15 -50mmol / 24 hours
Urate 1.2 -3.0mmol / 24 hours
Copper – <.6micromol / 24 hours

Pus cell and bacteria should be absent in urine. Their presence always indicates infection (pyelonephritis, urethratitis, uretitis, cystitis, etc.). If there are pus cells and bacteria, culture must be done to rule out infection. Pus cells can be easily identified after centrifuge and sedimentation.

Urine culture – Normally, kidney-filtered or bladder-stored urine is sterile. The small number of bacteria present in the urine while passed is due to contamination of bacterial flora in the urethra. If the result denotes more than 10,000 colonies of bacteria, then it is said to be confirmed bacterial infection or otherwise it may be due to urethral flora contamination. The common bacteria which infect are Coliforms, Enterococci, Gram negative rods, etc.

Bacteria will not sediment by centrifuge, so to identify it, culture or growth of bacteria in a medium is usually followed which can easily show the type of bacterial infection. Nowadays culture tests are done with sensitivity tests, so that the correct drug can be administered in the initial period itself.

Casts are coagulated proteins seen as sediments in urine, so proteinuria is the precursor of cast formation. The blood cells (RBCs & WBCs) and epithelial cells can get lodged to this and form erythrocyte casts, leucocyte casts and epithelial casts. In normal conditions, casts will not be seen in urine.
Hyaline casts – are protein casts which occurs usually after violent exercises and also in case of chronic kidney failure
Leucocytes casts occur after urinary tract infection
Erythrocyte casts occur in hypertension, anaemia, renal stones, urinary tract infection etc.
Epithelial casts show inflammation and degeneration of kidney

Crystal formation occurs in the urine when it gets supersaturated with the solutes. It can produce uroliathiasis: for example – stone formation from increased excretion of uric acid which may sediment and form crystals or stones. Likewise are the cystines and oxalates.

Round, brick red/orange sediment in the urine of children indicates Xanthine.
Pink or yellow colour crystals – cystines
Smooth and chalky – phosphates
Dark brown – oxalates

Red urine – The high intake of beetroot usually resemble blood in the urine; another factor which can mimic bloody urine is dyes and chemicals used in sweets. In diseased conditions, bloody urine (Haematuria) may occur due to infection or stones in kidney or bladder or ureter or urethra or due to infection of the prostate. Everyone should be ever careful if blood cells are present during urination since it indicates that the condition is serious. Most of the time, it is passed as microscopic haematuria (i.e. blood in the urine may not be visualised normally). But sometimes, in case of massive bleeding, urine appears as bloody or pinkish or smoky or deep brown, alarming the person. Even though we might pass 1-3 RBCs (red blood cells), elevated levels will usually indicate internal diseases or complications. The RBCs occur in the urine in abnormal conditions like kidney stones, cancer of the kidney or bladder or prostate, heavy urinary tract infection, sickle cell anaemia, etc.

Gravindex test for pregnancy – following a missed period, even within a week or so, pregnancy can be confirmed by detecting the presence of HCG (human chorionic gonadotrophin) in the urine. This lab test is now simplified by colour card test where everyone can use to test urine for pregnancy at home itself.

Even though urinalysis indicates a problem, finally to evaluate and analyse the effects and complication of the disease imaging studies like ultrasound scan, IVP, CT scan and MRI may be necessary to confirm and proceed to the treatment.

for new hope

Dr. S. Chidambaranathan, BHMS, MD (Homeo)

Laxmi Homeo Clinic

24 E. New Mahalipatti Road

Madurai, TN 625 001

India

Tel:  +91-452-233-8833 | +91-984-319-1011 (Mob)

Fax: +91-452-233-0196

E-mail:  drcheena@yahoo.com

www.drcheena.com  / www.drcheena.in

(Disclaimer - The contents of this column are for informational purpose only. The content is not intended to be a substitute for professional healthcare advice, diagnosis, or treatment. Always seek the advice of healthcare professional for any health problem or medical condition.)