Cholestatic liver disease or  primary biliary cirrhosis is an autoimmune liver disease  which leads to a process of progressive destruction of the bile canaliculi (small bile ducts) within the liver.  As a consequence of the destruction of these  ducts,  cholestasis occurs (bile builds up in the liver ) and in time the hepatic tissue is being damaged. This process will lead to hepatic fibrosis and cirrhosis. This disease affects to 1 in 3-4,000 people and it affects women more frequently than men, the sex ratio being around  9:1 (women to men).

The signs and symptoms of cholestatic liver disease are mainly common to all the chronic liver diseases.

Fatigue occurs in about 65% of the patients with cholestatic liver disease and in many cases is the first reported symptom. It exacerbates after meals and it may be associated with sleep abnormalities such as excessive daytime somnolence probably due to the disturbance of the  hypothalamic-pituitary-adrenal axis. Depression and obsessive-compulsive behavior may also be associated to this symptom.

Pruritus (itching) may occur in any liver disease but it occurs more commonly in primary biliary cirrhosis and in sclerosing cholangitis. In
some patients with  cholestatic liver disease the generalized itching may limit normal activities, lead to sleep deprivation, and it may a major impact on the overall quality of life. The pruritus, especially if severe may lead to skin excoriations which may become superinfected. The pathogenesis of pruritus is not well known but it seems to be related to the increased central opioidergic tone.

The patients with cholestatic liver disease will also have a higher risk of acquiring an infection. There have been performed many studies showing that incidence of bacterial infections in these patients is very high, and the incidence of nosocomial bacterial infection (infection acquired while being admitted into a hospital) is much higher than in the general population. It appears that these patientstend to develop many infections determined by gram-negative bacilli especially in the patients who have decreased gastric motility. This change (the decreased gastric motility) will lead to changes in the intestinal flora which will increase the risk of gram-negative bacteremia, through the disruption of the intestinal permeability barrier. Another cause which may predispose to bacterial translocation is gut wall edema, hypoalbuminemia and ascites fluid.

Cachexia and malnutrition are seen in many  patients with primary biliary cirrhosis. There are many factors contributing to the development of this sign: malabsorption of nutrients due to the intestinal edema, diarrhea the decreased bile flow, and the reduced hepatic deposits of  hydrosoluble vitamins. Anorexia results from fatigue and nausea, and the early satiety due to ascites , the decreased gastric emptying, and the psychological discomfort determined by the frequent hospitalizations will lead to a poor food intake. Moreover, the patients with primary biliary cirrhosis have an impaired intermediary metabolism as a result of increased  levels of proinflammatory cytokines and the altered balance of the hormones maintaining the metabolic homeostasis.

Other clinical manifestations of cholestatic liver disease are right upper quadrant discomfort (pain or tenderness -10%), hepatomegaly (increased size of the liver-25%), splenomegaly (spleen larger than normal -9%), hyperpigmentation (25%), xanthomas (cholesterol deposits seen in the palmar creases or above the eyes- 10%), and jaundice (10%).

Parkinson's disease is a motor system disorder, which is the result of the destruction of dopamine-producing neurons. The four major symptoms of Parkinson disease consist in tremor, ( trembling in arms, hands, legs, jaw) stiffness of the arms, legs and trunk (rigidity); bradykinesia, (the slowness of movement); and postural instability (impaired balance and lack of coordination). As the disease progresses and the symptoms become more obvious, patients will have trouble walking, talking, or completing simple tasks. Parkinson disease usually occurs people over 50 but there have been reported cases of early onset Parkinson disease.
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Early symptoms of Parkinson disease are subtle and develop gradually, going unnoticed even for years and the speed with whic the disease progresses varies from one patient to another.  As the disease progresses, the tremor, which affects Most of the Parkinson Disease patients,  may begin to interfere with their daily routine.  The tremor is characteristic: a rest tremor ( with a maximal intensity when the limb is resting and it disappears with voluntary movement and sleep); which it consists in a pronation - supination movement that is described as "pill-rolling" or "coin counting". Tremor affects in a greater extent the distal part of the limb and at the onset of the disease is usually unilateral.

Rigidity, determined by the muscular hypertonia (increased muscle tone) and articular stiffness, combined with the tremos produces a the typycal "cogwheel rigidity" a ratchety type of rigidity which occurs when the limb is passively moved. Joint pain may occur, frequently representing the first sign of the disease.

Bradykinesia (the slowness of movement) and akinesia (the absence of movement) will also occur as the disease aggravates. Bradykinesia is the most specific clinical aspect of Parkinson disease and it impairs not only the execution of a voluntary movement but also it affects the planning and the initiation of movement The performance simultaneous or sequential movements is also affected.The amplitude of the movements decreases too. Motor blocks, or gait freezing are a specific manifestation of akinesia . It represents a sudden episode of inability to move the feet and legs lasting  less than 10 seconds. Its intensity and duration may increase cluttered spaces usually when the patient approaches a destination.

The speech and the swallowing are also impaired, Parkinson Disease leading to : soft speech (hypophonia), monotonic speech (hoarse, soft speech), Drooling (determined by a weak swallow)most likely caused by a weak, infrequent swallow. The difficulties to swallow (dysphagia); which occurs in Parkinson Disease is probably determined either by an inability in initiating the swallowing reflex or by an impaired laryngeal or oesophageal movement (prolonged swallowing movements).

The neuropsychiatric features are either determined by the disease (dementia, loss of short term memory, difficulties in: differential allocation of attention,  set shifting, prioritizing and impulse control) or are a consequence of the impact hat the disease has on the patient's life and the life of his/her family (depression).