Most people with kidney disease are asymptomatic (have no symptoms) or may present with nonspecific complaints such asanorexia, fatigue and malaise. Because of this, many patients present to a specialist only when advanced kidney disease has developed. More specific symptoms of kidney disease include hypertension, nocturia, polyuria, hematuria (blood in urine), edema, or dark-colored urine. A medical history of diabetes and hypertension has an important diagnostic value. A history of recurrent urinary tract infections or kidney stones or a family history of kidney disease is also very important and should be mentioned when seeking medical advice.

High blood pressure or hypertension is very important because there is a vicious cycle between hypertension and kidney disease. Hypertension leads to arterial and capilar damage and blood vessels, and when this affects the arteries and capilaries inside the kidney, the kidney ability to remove properly the excess sodium and water from the body. As sodium and water accumulate, the blood pressure is raised even further,leading to an increased damage to the kidneys and so on.

Edema, or the swelling of the body parts, is also an important sign of kidney disease. The edema in kidney disease presents as a facial swelling and a puffy aspect of the skin around the eyes upon awakening, or swelling of the feet and ankles. Edema is a common symptom of other conditions as well, this being the reason why kidney problems may be overlooked. When the kidneys are distressed, they are unable to eliminate the excess of water and the toxins efficiently. As the amount of water in the body increases edema occurs, as the water infiltrates the subcutaneous tissue (the tissue under the skin).


Fatigue may be another early symptom of kidney disease. This symptoms occurs because the production of erythropoetin, a hormone which stimulates the production of red blood cells. The red blood cells transport the oxygen throughout the body. If the kidneys are impaired, the production of erythropoetin decreases and the number of erythrocytes (red blood cells) declines causing a condition named anemia, leading to hypoxia and a loss of energy.

Another  early sign of kidney disease is represented by the changes in the volume of urine eliminated daily (the urinary output). These changes include the need to urinate more frequently or less often or waking up during sleep. A low output of urine when still feeling the need to urinate accompanied by change in urine color, should determine one to go to a specialist immediately.

Phosphorus, which is normally eliminated in the urine, accumulates in the  body of  the patients with kidney failure. The build up of phosphorus chemical compounds may cause the skin to itch. Bad breath or bad taste in the mouth may also be determined by kidney disease because of the urea and waste products (resulted from the proteic metabolism) which may accumulate in the saliva.

Hirsutism, acne, chronic anovulation with consequent menstrual disorders are symptoms speciffically associated with disorders affecting androgen hormones production and metabolism in adolescent girls. In both the prepubertal boys and girls the androgen excess leads to premature pubarche ( the early development of pubic and axillary hair, acne, and/or adult-type apocrine odor which occurs before the age of eight years in girls and nine in boys.

Hyperandrogenemia is generally determined by the excessive androgen secretion by the adrenal gland's cortex, by the ovaries (in girls), or testes (in boys). Other clinical manifestations of hyperandrogenemia are represented by menstrual disorders, the enlargement of the clitoris, breast atrophy, masculine body habitus, voice changes and male-pattern baldness. The magnitude of the signs and symptoms of androgen excess are not always correlated with the serum androgen concentrations.

The symptoms of polycystic ovary disease usually begin around menarche . Premature pubarche, the result of early secretion of adrenal steroids, may be heralding the following disturbances. Almost 80% of the girls with polycystic ovary disease first notice the hirsutism.

Hirsutism representss the presence of excessive  hair growth which appears in a male pattern in women.It usually presents as the appearance of coarse terminal hairs in areas known as androgen-dependent in a female. The parents and the patients often consider hirsutism as a strictly cosmetic problem and may postpone seeing a physician.



The women with polycystic ovary disease often have a LH hypersecretion which commonly leads to chronic anovulation which most often manifests as oligomenorrhea (less than nine menses with a reduced menstrual flow per year) or amenorrhea. An increased risk of endometrial hyperplasia may occur due to these menstrual abnormalities.  There should be made a difference between primary amenorrhea and secondary amenorrhea. Primary amenorrhea represents the absence of menarche (the first period) by the age of 16 in the presence of normally developed breast and pubic hair.

The absence of menses for three  months (consecutively) after a period or regular (relatively regular) menses represents secondary amenorrhea. The anovulatory cycles may have as a consequence dysfunctional uterine bleeding and lead to a decreased fertility and later in life miscarriage or ectopic pregnancy can occur due to the endometrial abnormalities

A great amount of women with polycystic ovary disease are overweight; even obese. Even though obesity is not considered to be the most relevant feature of the disease, the excess weight can lead to an exacerbation of the associated metabolic disturbances characterising the disease.

The teenage  and adult women with polycystic ovary disease have a higher risk to develop the metabolic syndrome. This syndrome consists of a wide range of disturbances including hypertension, insulin resistance, and dyslipidemia.  The insulin resistance will lead to an increased risk for impaired glucose tolerance and diabetes mellitus type 2.

Phenylketonuria (PKU disease) is an autosomal recessive genetic disorder which determines a deficiency in the enzyme named phenylalanine hydroxylase, necessary in the metabolism of phenylalanine. If phenylalanine hydroxylase is deficient, phenylalanine will accumulate and it will be converted into phenylpyruvate. The degree of enzyme deficiency, and as a consequence, the severity of the disease depends on the specific mutation and it varies among patients. At the moment, there is no cure for this disease, but some treatments are available.

The early diagnosis of the disease is very important and a genetic routine screening should be performed in every newborn , because at birth most newborns with the disease are clinically normal and do not display any . The clinical features of PKU disease will become obvious over several months as phenylalanine and phenylpyruvirate accumulates.

The typical sign of untreated PKU disease is severe mental retardation. Children also tend to be hyperactive and may develop a rash similar to infantile eczema. Albinism may occur due to the impaired synthesis of melanin (the pigment that gives the colour of the skin, eyes and hair) , but it may go unnoticed in the milder forms of the disease when the babies are considered to have blonde hair and blue eyes.

Other signs of nervous system function disturbances may be more subtle such as more active muscle tendon reflexes and an increased muscle toneor be more obvious such as seizures.

The untreated children may also have: microcephaly (smaller than normal head), proeminent zygomatic and maxilar bones, widely spaced teeth, poor development of tooth enamel, a delayed growth. With treatment and a good dietary control, the disease impact on the physical and mental development are minimized. Recent studies however indicate that the loss of dietary control during chilcdhood can have a great impact on cognitive development. These studies show that the people with PKU should maintain a strict dietary control throughout their lifetime. If development problems arise and dietary causes are suspected an intervention should be instituted as soon as possible

The excess of phenylacetic acid in perspiration leads to a specific odour of the babies diagnosed with the PKU disease. This smell has been described as musty or mousey.

The dermatological features of the disease are: an eczematoid skin rash, coarse skin and reduced pilosity. Other skin problems are represented by dry skin and severe itching.

The women with PKU disease who want to have a baby must to follow the PKU diet in order to avoid the high levels of phenilalanine which may affect the future physical and mental development of the fetus but they should also get enough nutrients to support the fetus.

Scurvy is a  serious disease determined by vitamin C defficiency , a substance of extreme importance in the synthesis of collagen. The impaired collagen syntetis results in the weakening of the small blood vessels (capillaries), which causes , bleeding of the gums, loosening of the teeth and tissue hemorrages with consequent anemia, fatigue and general debility. The disease has been mentioned in ancient documents (Hippocrates) , but the discovery of the link between the diet and the disease has not been made until the experiences of the 18 th century sailors have been studied. The simple observation that  the consumption of fresh fruit helped to prevent the disease was made by James Lind in his book, A Treatise of the Scurvy (1753)

Nowadays scurvy still occurs primarily in teenagers with anorexia or in the elderly, isolated individuals with alcoholism.

The main vitamin C deficiency sign is represented by the impaired production and maintenance of collagen, affecting all fibrous tissues: the matrix of cartilages, the matrix of the bones, the dentine and the vascular endothelium (the non-epithelial structures). As a result the capilaries will develop an increased permeability to the red blood cells, leading to hemorrhages. As the disease progresses, affecting the collagen from the bone matrix, the formation of new bone tissue is stopped but the bone absorption keeps going on and so the bones will become more fragile and friable at the growing ends. The impaired collagen formation will also affect the skin, leading to and increased time for wound healing and an increased risk of infection. In other situations, the collagen structures formed due to the process of wound healing will be absorbed and the wounds will reopen.

Other important symptoms of the disease are the gradual weakening, sunken eyes, tender gums, even loosening and loss of teeth , pain in the skeletal muscles,  and internal bleeding leading to anemia and its symptoms.

Psoriasiform hyperplasia is a characteristic dermatological clinical aspect of scurvy accompanied by the pallor of the lower half of the epidermis.Other dermatological manifestations of the disease are: a rash determined by tiny bleeding spots around the hair follicles, hyperkeratosis and the fact that the skin of the people with scurvy bruises easily.

In the more advanced stages of the disease more symptoms occur. The general edema and oligurai are determined by kidney damage.

Bone involvement is a typical sign for infantile scurvy. The bone becomes brittle with consequent microscopic fractures of the spicules between the shaft and calcified cartilage. Subperiosteal hemorrhage will also occur, because these microscopic fractures loosen the periosteum.

Petechial hemorrhage of the skin and mucous membranes may occur, but only in the severe cases, signs of severe internal bleeding (hematuria, hematochezia, and melena ) have been documented.

HBSC disease or sickle-cell disease, (also known as sickle-cell anaemia, siclemia, or drepanocytosis), is a life-long hemoglobinopathy characterized bya biochemical lesion consisting in the replacement of the glutamic acid from the sixth position of the beta chain of hemoglobin with valin, resulting a new type of hemoglobin, with new properties, and so, the red blood cells will have an abnormal, sickle shape. This form has as a consequence a decreased cell flexibility and a risk of various complications. The life expectancy in people with siclemia is shortened, and the studies performed have reported an average life expectancy of 42 years for men and 48 years for women. The disease is determined by a mutation in the hemoglobin gene.

The symptoms of HbSC disease (or sickle-cell disease) depend on whether the patient is homozygot for the mutated gene or not.

The heterozygotic form is usually asymptomatic , the carriers being accidentally discovered on the ocasion of medical investigations for other conditions. There should be known that in some situations such as diving or general anaesthesia thrombosis may occur, leading to infarction affecting virtually any organ.

The homozygotic form has the signs and symptoms determined by two causes: hemolysis and occlusion.

The hemolysis determines the chronic hemolytic anemia which is responsible of the aspect of the characteristic aspec of the children with HbSC disease: short body, long legs and arms, lumbar lordosis and cranial abnormalities. The jaundica is variable, depending on the degree of hemolysis. The spleen does not develop normally due to the reccurent infarctions and in adult life the atrophy and fibrosis will lead to a condition called autosplenectomy.

Almost 30% of the patients will also develop pigmentary gallstones. In these cases the cholecistectomy ia not indicated, unless the colic pain occurs.  The differential diagnosis in this case must be made between the pain produced by acute cholecystitis and the pain from cholelithiasis determined by siclemia.

Splenomegaly may occur if the HbSC disease is associated with other blood disorders.

The occlusion ofthe blood vessels may affect any organ or tissue, leading to infarction. The vaso-occlusive crisis is determined by the sickle-shaped red blood cells  obstructing the capillaries and restricting the blood flow to a tissue or organ, resulting in pain and ischemia leading to organ damage. The severity and duration of these crises vary considerably.

Another classic form of sickle crisis is the acute chest syndrome, a syndrome characterised by fever, dyspnea (shortness of breath) , chest pain and pulmonary infiltrate on a chest X ray. Given the fact  that pneumonia and sickling in the lung have all these symptoms the patient should be  treated for both conditions. This syndrome may be triggered by respiratory infections,  atelectasis, opiate administration, bone-marrow embolisation, or , possibly, by surgery.

Hashimoto's thyroiditis, Hashimoto's disease or chronic lymphocytic thyroiditis are medical terms reffering to a thyroid autoimmune disorder in which the body's own T-cells attack the folicular thyroid cells. Hashimoto's disease is the first documented autoimmune disease and it is considered to be the most common cause of hypothyroidism in the United States where almost 2 in 1000 people develop this disease. This disorder affects far more  women than men ( 20 :1), and its prevalence peaks between 45 and 65 years of age. In Europe a form of atrophic autoimmune thyroiditis is more frequent than Hashimoto's disease.


The underlying specific immune mechanisms of systemic destruction of the thyroidian cells has not been clearly determined. There has been documented the presence of various autoantibodies may be present against TSH receptors and thyroglobulin even though a small percentage of the people who develop the disease may not have these antibodies. Another small percentage of the general population may have these antibodies in their blood but without ever developing the disease. Many patients have a family history of thyroid disorder and the studies have shown that the incidence of the disease is increased in the people with chromosomial disorder, especially 21 trisomy (Down's syndrome), X trisomy , Klinefelter's syndrome, X monosomy (Turner Syndrome)



The disease has an insidious onset and it consists in a slow, constant destruction of the thyroid cells resulting in the gland's inability to produce sufficient thyroid hormone - hypothyroidism. During the course of the disease there may be periods when the thyroid function may spike, even leading to a temporary hyperthyroidism, followed invariably by returns to hypothyroidism. These variations and bouncing between hypothyroidism and hyperthyroidism is a characteristic feature of Hashimoto's disease. So, for example, periods specific to hyperthyroidism with symptoms such as anxiety, insomnia, diarrhea, weight loss may be followed by depression, fatigue, constipation and weight gain.

Many patients do not have any  symptoms and seek medical assistance just because of the specific sign of the disorder - the goiter.  The goiter (the gradual enlargement of the thyroid gland) is usually asymptomatic and painless, but in some cases the patients complain of a feeling of local pressure, voice changes (hoarseness) and dysphagia (pain or difficulty while swallowing).
In the early stages of the disease depression and anxiety may occur but an underlying depression may also be aggravated by Hashimoto's disease.



The disease leads to hypercolesterolemia (high colesterol levels) with consequent predisposition to heart disease but heart disease may be determined also by the impact of the low levels of thyroid hormones on the cardiac activity, leading to contraction and rhythm disorders.Other clinical features of the disease are dry brittle hair and nails, hair loss, osteoarticular pain, insomnia, fatigue and weight changes.

The severity of the disease may decrease during pregnancy and there have also been documented very few cases of thyroid disorders in pregnant women, due to the fact that the immune system is slightly depressed during pregnancy in order to protect the fetal development. However, during the postpartum period the disease may increase in severity in the post partum period. There should be known that hypothyroidism may affect fetal development, leading to an increased risk of miscarriage or malformations (such as cleft lip or cleft palate) or to an impaired psychomotor development and a lower IQ.

The disorders affecting the gallbladder and the biliary tract are extremely common. The main role of the gallbladder  and biliary tract is to transport the bile into the intestine, which is essential for the digestion and absorbtion of fat. The symptoms of gallbladder disease are determined not only by the disease but also by the impact of the disease on normal digestion.

The most common gallbladder disorder is represented by gallstones, and some studies studies performed in the USA and Europe, have shown that about 15% of adults have gallstones. Most people with gallstones do not have any symptom (about 60%), in up to 30% of the people biliary colic or chronic cholecystitis will occur, and almost 15%  will develop acute complications. The main cause of all the clinical features of gallstone disease is represented by the obstruction of the biliary tract, obstruction which may occur at any level of biliary tract ( the cystic duct, common hepatic duct, common bile duct or ampulla of Vater).

The symptoms occur due to the contraction of the gallbladder during a transient obstruction by gallstones, but a persistent obstruction  leads to an inflammation or an infection of the gallbladder leading to consequent acute colecystitis. Biliary colic represents the common symptom of gallbladder disease and it presents as an intermittent pain which occurs in the right-upper quadrant. The other symptoms may be  nonspecific and include: nausea and vomiting .

Chronic cholecystitis refers to the "nonacute" symptoms determined by the presence of gallstones over a longer period of time (days or even years). Biliary pain is represented  typically by a steady ache in the epigastric region or in hte right upper quadrant, with a sudden onset.  Nausea and vomiting may occur, as well as  nonspecific symptoms such as dyspepsia, fatty food intolerance, heartburn, bloating and flatulence.



Acute cholecystitis consists in the distention, inflammation, edema and secondary infection of the gallbladder, as a result of the obstruction of the biliary tract by gallstones, by cancer or  by sludge. The characteristic clinical feature of acute cholecystitis is the acute onset of pain in the right upper quadrant, lasting for several hours. The severity of the pain increases, and the pain tends to localize to the epigastrium or right hypochondrium radiating to the right lumbar, scapular areas.  Other common features are nausea, vomiting and mild fever and in some cases a mild jaundice may be observed.

Acute (suppurative) cholangitis is a life-threatening infection and inflammation of the biliary tract determined by choledocholithiasis. The classic clinical manifestation are Charcot's triad : abdominal pain,  fever and jaundice. This disorder is a medical/surgical emergency and if untreated it has a fast evolution towards sepsis, shock, and death.

Primary sclerosing cholangitis is an idiopathic condition  which consists in a chronic inflammatory fibrosis and consequent obliteration of the hepatic bile ducts. The clinical manifestations of primary sclerosing cholangitis are various and range from asymptomatic patients with abnormal levels of liver enzymes  to recurrent  fever,  abdominal pain, chills, and jaundice.

Coughing up blood or hemoptysis is a serious sign because it frequently indicates a serious underlying lung disease. Because many of the lung disease heralded by this sign are treatable, systematic and through evaluation is required in order to discover hemoptysis etiology.

The first step when evaluating hemoptysis is to establish if it is really hemoptysis (blood from the bronchial tree or lungs) or from other sites, mimicking hemoptysis. In most cases, the patient's clinical history suggests that the expectorated blood is indeed being coughed up from the lungs or respiratory tract but in some cases there may occur difficulties in distinguishing whether the blood source is  the respiratory system or two other sites: bleeding in the sinuses, upper respiratory tract or in the nasopharynx, or blood which originates the gastrointestinal tract and was regurgitated. A patient medical history of frequent nosebleeds and hoarseness or other voice changes suggests bleeding from the upper respiratory tract. The presence of gastrointestinal symptoms usually suggests hematemesis. Moreover, an emesis (vomit) with a coffee ground aspect may be determined if the blood from a respiratory source has been swallowed.

The most common cause of hemoptysis is tuberculosis. The hemoptysis resulting from this disease is usually mild to moderate and is commonly associated with other signs and symptoms such as unexplained weight loss, purulent sputum (thick, yellowish- white discharge) and a history of exposure to Mycobacterium tuberculosis.

Bronchitis, the inflammation and swelling of the bronchi represents another common cause of hemoptysis. In this case. the blood originates from recurrent coughing which irritates and eventually breaks the respiratory mucosal lining. The hemoptysis in bronchitis is usually mild and is usually associated with a purulent sputum , low-grade fever and wheezing.

Bronchiectasis, the chronic dilation with a consequent infection of the bronchioles and bronchi determined by the bronchial obstruction is another cause of hemoptysis. The patients with bronchiectasis often present with a mild to moderate hemoptysys, a severe cough accompanied by a  chronic purulent sputum. Lung cancer and bronchogenic carcinoma are important causes of hemoptysis. In these cases, the bleeding is the result of the necrosis of the tumor ), the rupture of  some small blood vessels in the tumor area, of the tumor invading activity of one of the pulmonary blood vessels (in which case massive bleeding occurs).

In pneumonia ( lung infection determined by a vaste variety of microorganism) other symptoms beside hemoptysis are: a high fever, cough, and chest pain.Other less common causes of hemoptysis are: pulmonary infarction or embolism, pulmonary AVM, trauma, heart diseases, vascular disorders, drug use, anticoagulant medication, pulmonary endometriosis, aspergilosis, and autoimmune disorders.

Acid reflux disease, or more correctly, gastroesophageal reflux disease is the result of the failure of the body's normal antireflux mechanism to protect against the effortless movement of the gastric content from the stomach to the upper pars of the digestive tract (esophagus). Gastroesophageal reflux is a normal physiological process, with no signs, symptoms or consequent mucosal damage but in gastroesophageal reflux disease symptoms of heartburn and acid regurgitation occur.

The signs and symptoms of gastroesophageal reflux disease may be esophageal (heartburn , acid reflux, odynofagia) or extraesophageal.

The classical symptom for this disorder is heartburn.


The patients usually complain of a burning heeling rising from the stomach or epigastric area toward the neck and throat. This symptom usually manifests or exacebates postprandially, especially if the patient has eaten spicy foods, fats, chocolate or drank alcohol. Heartburn may also be exacerbated by bending over or recumbency, and , if it occurs at night it will interfere with sleeping. Inspite of the fact that this symptom is an important diagnostic clue, its intensity, frequency and duration is not a parameter in order to evaluate the severity and the degree of mucosal damage.

Another common symptom of gastroesophageal reflux disease is acid regurgitation. The postprandial effortless regurgitation of acid fluid, especially if exacerbated by recumbency is a very suggestive feature of gastroesophageal reflux disease. Most patients presenting with this symptom have a associated gastroparesis and a reduced LES (lower esophageal sphincter) pressure. In time, most of the patients will also develop esophagitis.

More than 40% of the patients complain of dysphagia which begins as a longstanding heartburn progressing slowly towards a dysphagia for solid foods. Still, most of them have a normal appetite and so weight loss occurs only rarely (in about 5% of the patients, most of them with severe esophagitis).

Waterbrash is a less common symptom of the disease and it consists in the spontaneous, sudden apparition of a salty or sour fluid which is caused by the salivary glands's  response to the disease.

Odynophagia or pain in swallowing may occur after the development of ulcerative esophagitis but it may be caused by a variety of other disorders, most of them with an infectious etiology. It is highly important that the underlying cause of odynophagia be sought.Other less common symptoms of gastroesophageal reflux disease are nausea,  hiccups, burping and vomiting.

The extraesophageal manifestations of the disease are: noncardial chest pain mimicking angina pectoris and which usually worsens after meals, chronic cough, asthma (there have been studies suggesting that gastroesophageal disease may have an impact on triggering and/or aggravating asthma),  posterior laringitis, vocal cord ulcers and granulomas, and dental erosion.

Peptic ulcers are lesions in the gastrointestinal lining, extending through the layer called muscularis mucosae. These lesions usually persist and are dependent on the acid-peptic characteristics of the gastric juice. The most important causes of this disease are the infection with Helicobacter pylori and the use of nonsteroidal antiinflamatory drugs (NSAID), including ibuprofen and aspirin but the patogenesis is multifactorial, the disease being favored by a variety of internal and environmental factors (gastric ph, hereditary factors, alcohol use, smoking, infectious agents and so on).

The classic ulcer symptom is acid dyspepsia, characterized as a burning epigastric pain with a strong tendency to occur when gastric juice is secreted in the absence of a food buffer (hunger pain), especially at night, Antisecretory drugs and food relief the pain, so many authors say that the patients "feed their ulcers".


The pain is localized in the epigastrium but it may also localize in the upper left quadrant or hypochondrium. the pain may also radiate to the back. Even after up to 3 years after the infection with Helybacter pilory has been eradicated, many patients complain of dyspepsia, probably related to sensitization of the nerve endings as a response to tissue injury.

Gastroesophageal reflux disease ) occurs in up to 60% of the patients with peptic ulcer disease. The disease is evident by esophagitis, heartburn and acid relux and there is well known that the obese patients are more predisposed to gastroesophageal reflux disease.

If the patient has not been using nosteroidal antiinflammatory drugs, the complications are mainly associated with a chronic peptic ulcer and mainly consist in the development of ulcer symptoms or in a change in the previous symptom pattern.
The most common complication of peptic ulcer is represented by penetrating ulcers. A penetrating ulcer usually presents with a more localized and intense pain (unlike in uncomplicated disease where the pain is perceived more as a vague visceral one). In pyloric outlet obstruction vomiting is a classical symptom and perforation is indicated by a diffuse, severe abdominal pain, with a sudden onset. Dizziness, melena (tarry, black stools), nausea and hematemesis (vomiting blood) may herald a hemorrhage.

Penetrating ulcers may also lead to fistulae. In the penetrating ulcers localized on the anterior gastric wall colonic fistulae may occur, and the patient presents halitosis (bad-smelling breath), feculent vomiting, dyspepsia, weight loss and postprandial diarrhea. A posterior perforation of an ulcer will have an insidious onset, with protean symptoms (which mainly consist in upper abdominal pain), caused by a localized retroperitoneal abscess or the contamination of by the peritoneal cavity. Hepatic penetration has also been documented.