Main clinical symptoms in chronic enteritis and colitis.

Defence of Case History.

Main symptoms and syndromes in kidney diseases – acute and chronic glomerulonephritis and pyelonephritis. Syndrome of renal failure

I. Chronic diseases of small intestine: (Crohn’s disease:

aetiology, diagnosis, differential diagnosis, treatment, complications).

 

Crohn’s disease (CD) and ulcerative colitis (UC) are characterized by chronic inflammation at various sites in the GI tract. Both cause diarrhea, which may be profuse and bloody. Certain differences in disease patterns justify a distinction between Crohn’s disease and ulcerative colitis, although groupings and subgroupings are somewhat artificial. Some cases are difficult, if not impossible, to classify.

The term colitis applies only to inflammatory disease of the colon (eg, ulcerative, granulomatous, ischemic, radiation, or infectious colitis). Spastic or mucous colitis is a misnomer often applied to a functional disorder that is more properly described as ir­ritable bowel syndrome.

CROHN’S DISEASE –

A nonspecific chronic transmural inflammatory disease that most commonly af­fects the distal ileum and colon but may occur in any part of the GI tract.

Etiology and Epidemiology

The fundamental cause of Crohn’s disease is unknown. Evidence suggests that, a genetic predisposition leads to an unregulated intestinal immune response to an environ­mental, dietary, or infectious agent. However, no inciting antigen has been identified. Cigarette smoking seems to contribute to the development or exacerbation of Crohn’s dis­ease.

Pathology

The earliest mucosal lesion of Crohn’s disease is crypt injury in the form of inflamma­tion (cryptitis) and crypt abscesses, which progress to tiny focal aphthoid ulcers, usually located over nodules of lymphoid tissue. In some cases, these lesions regress; in others, the inflammatory process evolves with influx and proliferation of macrophages and other inflammatory cells, occasionally forming noncaseating granulomas with multinu­cleated giant cells.

Transmural spread of inflammation leads to lymphedema and bowel wall thickening, which may eventually result in extensive fibrosis. Development of patchy mucosal ul­cers and longitudinal and transverse ulcers with intervening mucosal edema frequently creates a characteristic cobblestoned appearance. The attached mesentery is thickened and lymphedematous; mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge. Transmural inflammation, deep ulceration, edema, muscular proliferation, and fibrosis cause deep sinus tracts and fistulas, mesenteric abscesses, and obstruction, which are the major local complications. Granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the rowel wall and are occasionally seen at laparotomy or laparoscopy as miliary nodules. Although pathognomonic, granulomas are absent in up to 50 % of patients and are therefore not essential to diagnose Crohn’s disease. They appear to have no definitive bearing on the clinical course.

Segments of diseased bowel are characteristically sharply demarcated from adja­cent normal bowel (“skip areas”)—thus the name regional enteritis. Of all cases of Crohn’s disease, about 33% involve the ileum ileitis); about 45% involve the ileum and co­lon (ileocolitis), with a predilection for the right side of the colon; and about 15 % involve the colon alone (granulomatous colitis). Occasionally, the entire small bowel is involved jejunoileitis), and rarely, the stomach, duodenum, or esophagus. The perianal region is also affected in 1/4 to 1/3 of cases.

VIDEO 1 (normal intestine)

 

         The spectrum of Crohn disease presentations includes (a) gastroduodenitis (7% of patients), (b, c) jejunoileitis and ileitis (33% of patients), (d) ileocolitis (45% of patients), and (e) colitis (15% of patients).

Symptoms, Signs, and Complications

Chronic diarrhea with abdominal pain, fever, anorexia, weight loss, and a right lower quadrant mass or fullness are the most common presenting features. However, many patents are first seen with an acute abdomen that simulates acute appendicitis or intestinal obstruction. About 1/3 of patients have a history of perianal disease, especially fissures and fistulas, which are sometimes the most prominent or even initial complaint. In children, extraintestinal manifestations frequently predominate over GI symptoms. Arthritis, fever of unknown origin, anemia, or growth retardation may be a presenting symptom, and abdominal pain or diarrhea may be absent.

The most common patterns of Crohn’s disease pathology are (1) inflammation char­acterized by right lower quadrant abdominal pain and tenderness; (2) recurrent partial ob­struction caused by intestinal stenosis and leading to severe colic, abdominal distention, constipation, and vomiting; (3) diffuse jejunoileitis, with inflammation and obstruction resulting in malnutrition and chronic debility; and (4) abdominal fistulas and ab­scesses, usually late developments, often causing fever, painful abdominal masses, and generalized wasting.

Enterocutaneous fistulae in Chrohn’s disease

 

Obstruction; development of enteroenteric, enterovesical, retroperitoneal, or enterocutaneous fistulas; and abscess formation are common complications of inflamma­tion. Intestinal bleeding, perforation, and small-bowel cancer develop rarely. When the colon alone is affected, the clinical picture may be indistinguishable from that of ulcer­ative colitis.

 

         Endoscopic spectrum of Crohn disease includes (a) aphthous ulcerations amid normal colonic mucosal vasculature; (b) deeper, punched-out ulcers in ileal mucosa; (c) a single colonic linear ulcer; and (d) deep colonic ulcerations forming a stricture.

Extraintestinal manifestations are cat­egorized as:

     Complications that usually parallel the activity of the intestinal disease and possibly represent acute immunologic or microbiologic concomitants of the bowel inflam­mation: peripheral arthritis, episcleritis, aphthous stomatitis, erythema nodosum, and pyoderma gangrenosum. These manifestations may be reported by > 1/3 of patients hospitalized with inflammatory bowel disease. They are twice as common when colitis is present as when disease is confined to the small bowel. When extraintestinal manifestations  occur, they are multiple in about 1/3 of patients. Disorders associated with inflammatory bowel disease but running an  independent course: ankylosing spondylitis, sacroiliitis, uveitis, and primary sclerosing cholangitis. The genetic association of these syndromes and of Crohn’s disease (and ulcerative colitis) with the HLA antigen B27 is discussed under the extracolonic complications of ulcerative colitis, below. Complications that relate directly to dis­rupted bowel physiology: kidney stones from disorders of uric acid metabolism, impaired urinary dilution and alkalinization, and excessive dietary oxalate absorption; urinary tract infections, especially with fistulization into the urinary tract; and hydroureter and hydronephrosis from ureteral compression by retroperitoneal extension of the intes­tinal inflammatory process. Other bowel-related complications include malabsorption, especially in the face of extensive ileal resection or bacterial overgrowth from chronic small-bowel obstruction or fistulization; gallstones, related to im­paired ileal reabsorption of bile salts; and amyloidosis, secondary to long-standing inflammatory and suppurative disease. Thromboembolic complications may oc­cur, usually with severe disease activity, as a result of hypercoagulability associated with altered levels of clotting factors and platelet abnormalities.

Diagnosis

Crohn’s disease should be suspected in a patient with the inflammatory or obstructive symptoms described above and in a patient without prominent GI symptoms but with perianal fistulas or abscesses or with otherwise unexplained arthritis, erythema no­dosum, fever, anemia, or stunted growth (in a child).

Laboratory findings are nonspecific and may include anemia, leukocytosis, hypoalbuminemia, and increased levels of acute-phase reactants reflected in elevated ESR, C-reactive protein, or orosomucoids. Elevated alkaline phosphatase and γ-glutamyltranspeptidase accompanying colonic disease often reflect primary sclerosing chol­angitis.

Definitive diagnosis is usually made by x-ray. Barium enema x-ray may show reflux of barium into the terminal ileum with irregu­larity, nodularity, stiffness, wall thickening, and a narrowed lumen.

              X-ray showing abnormal terminal ileum in Crohn’s disease

 A small-bowel series with spot x-rays of the terminal ileum usually most clearly shows the nature and extent of the lesion. An upper GI series without small-bowel follow-through usually misses the diagnosis.

In advanced cases, the string sign may be seen with marked ileal strictures and sepa­ration of bowel loops. In earlier cases, x-ray diagnosis may sometimes be difficult, but air double-contrast barium enema and enteroclysis may show superficial aphthous and linear ulcers. In questionable cases, colonoscopy and biopsy may help confirm the diagnosis of Crohn’s colitis and allow direct visualization and biopsy of the terminal ileum. Upper GI endoscopy may identify gastroduodenal involvement in Crohn’s disease patients with upper GI symptoms. Although CT can detect extramural complications (eg, fistulas, abscesses, masses), it is not routinely needed for initial diagnosis. Ultrasound may help delineate gynecologic pathology in women with lower abdominal and pelvic pain.

Differential Diagnosis

Differentiation from ulcerative colitis may be difficult in the 20% of cases in which Crohn’s disease is confined to the colon (Crohn’s colitis). The principal differential diagnoses are acute infectious (self-limited) colitis and ulcerative colitis. Acute infec­tious colitis is best established by stool culture, rectal biopsy, and watchful waiting. Dif­ferentiating ulcerative colitis is detailed in Table 1. Although perinuclear antineutrophil cytoplasmic antibodies are present in 60 to 70% of ulcerative colitis patients and in only 5 to 20% of Crohn’s disease patients, and anli-Saccharomyces cerevisiae antibodies are relatively specific for Crohn’s disease, these tests are not sufficiently refined in routine clinical application as to reliably separate the two diseases.

Crohn’s disease of the small bowel (ileitis) requires differentiation from other inflam­matory, infectious, and neoplastic disorders in the right lower quadrant. If in the acute presentation a prior history of chronic bowel symptoms has not been elicited, ileitis may be first diagnosed during surgical exploration for suspected acute appendicitis. Periappendiceal abscess may produce more chronic symptoms and thus be more difficult to diagnose clinically.

Pelvic inflammatory disease, ectopic preg­nancy, and ovarian cysts and tumors also produce right lower quadrant inflammatory signs and must be ruled out when considering Crohn’s disease in women. Cancer of the cecum, ileal carcinoid, lymphosarcoma, systemic vasculitis, radiation enteritis, ileocecal TB, and ameboma may mimic the x-ray findings of Crohn’s disease. AIDS-related opportunistic infections (eg, Mycobacterium avium-intracellulare, cytomegalovirus) must also be considered as causes of localized il­eitis. Yersinia enterocolitica enteritis must be excluded if an inflamed, edematous terminal ileum and associated mesenteric adenitis are seen during surgery for acute right lower quadrant pain. Although Yersinia enteritis is self-limited without chronic intestinal se­quelae, the initial clinical picture may be indistinguishable from Crohn’s disease, so ap­propriate serologic and bacteriologic studies are necessary. In questionable cases, a 3-mo follow-up x-ray of the terminal ileum is valuable, because Yersinia enteritis will usually resolve completely by this time but Crohn’s disease will not.

Nongranulomatous ulcerative jejunoileitis has features of both Crohn’s disease and sprue, with malabsorption, small-bowel ulceration, and villous atrophy, but it lacks granulomatous pathology, fistulization, and extraintestinal manifestations of Crohn’s disease. Eosinophilic gastroenteritis generally has prominent gastric involvement (rare in Crohn’s disease) and is often associated with peripheral eosinophilia, which is the clue to diagnosis.

Prognosis

Although spontaneous remission or medical therapy may result in a prolonged asymptomatic interval, established Crohn’s disease is rarely cured but instead is characterized by intermittent exacerbations. In the absence of surgical intervention, the disease never extends into new areas of small bowel beyond its initial distribution at first diagnosis. With judicious medical and, where appropriate, surgical therapy, most patients with Crohn’s disease function well and adapt successfully. Disease-related mortality is very low and continues to decrease.

GI cancer, including cancer of the colon and small bowel, is the leading cause of Crohn’s disease-related death. Patients with long-standing Crohn’s disease of the small bowel are at increased risk of small-bowel cancer, with bowel in continuity as well as in bypassed loops. Furthermore, patients with Crohn’s disease of the colon have a long-term risk of colorectal cancer equal to that of ulcerative colitis, given the same extent and duration of disease.

Approximately 70% of Crohn’s disease pa­tients ultimately require surgery. Furthermore, Crohn’s disease is likely to recur even after resection of all clinically apparent disease.

 

 

II. Chronic diseases of large intestine: irritable bowel syndrome (aetiology, diagnosis, differential diagnosis, treatment, complications).

EPIDEMIOLOGY

         The symptoms associated with irritable bowel syndrome (IBS) are experienced by up to 20% of the population in the West. Although most sufferers will not consult a doctor, the condition still represents 50% of referrals to gastroenterologists. It is a transcultural condition and and is recognised in Africa, India and China. It is more common in urban populations, and is twice as prevalent in women. Symptoms tend to begin in the teens and twenties and decrease with age but the condition may be lifelong.

 

CLINICAL FEATURES (Fig. 1)

There is a host of symptoms that are associated with IBS but the following are the most important.

 

Fig. 1 Clinical features of IBS.

Abdominal pain

         This is the central feature and is usually described as colicky or constant, particularly in the lower abdomen or left iliac fossa. However, the pain may take on a variety of qualities and may be located anywhere within the abdomen. The intensity of the pain varies from intermittently, mildly annoying to extremely severe. It may be present at any time of day or night but it is unlikely to awaken sufferers from their sleep. It is frequently worsened by eating and relieved by defaecation.

Altered bowel habit.

It is worth remembering that the range of normality for defaecation is between once every 3 days and three times a day. The bowel habit in IBS is most often alternating in that sufferers describe periods of infrequent, hard often ‘pellet-like’ motions interspersed with increased frequency of looser stools. It is usually possible to determine a diarrhoea-or constipation- predominant IBS type, which has implications for treatment strategies. There is often urgency, a feeling of incomplete evacuation and passage of mucus associated with defaecation. Rectal bleeding, steatorrhoea and nocturnal defaecation are not features of IBS and warrant further investigation. Passage of mucus is often described as being increased by sufferers but a mechanism for this has not been found nor has it been reliably documented.

Bloating.

A sensation of abdominal distension is often described although it is quite difficult to demonstrate this consistently in IBS sufferers. Younger women report that they feel as if they are 9 months pregnant. This symptom may be the result of increased intestinal gas, which is probably swallowed air, but may also reflect altered intestinal motility.

Non-colonic gastrointestinal symptoms.

Frequent associated symptoms are of heartburn, nausea, postprandial fullness and pain which may be attributable to the gallbladder or biliary tree. This may be due to a generalized smooth muscle abnormality.

Extra-intestinal symptoms.

These include urinary frequency and dysuria. Dyspareunia may be present if specifically enquired about, and there may be features of fibromyalgia or chronic fatigue syndrome. Psychological factors may be relevant as there does appear to be an increased incidence of depressive illness and neuroticism amongst sufferers. In order to try to standardise the diagnosis, first Manning in 1978 described a series of symptoms which positively discriminated for IBS and subsequently in Rome these symptoms were refined (Table 1). However, these symptoms commonly occur in other organic gut conditions.

PATHOPHYSIOLOGY

                  

Table 1 Rome criteria for the diagnosis of IBS

Perhaps because of the heterogeneous nature of the condition and lack of a definitive diagnostic test, elucidating the cause or causes of symptoms has been unsuccessful. Although no single, consistent feature has been identified, abnormalities have been detected in:

• gastrointestinal motility – there are shorter transit times and hypomotility in diarrhoea-predominant IBS, and reduced, high  amplitude, peristaltic contractions in constipation-predominant IBS. The observed motility changes, however, do not correlate well with clinical features.

• altered visceral sensation – increased sensitivity to inflated balloons in both small and large bowel has been demonstrated and increased rectal sensitivity is a common finding.

• psychological abnormalities – both sufferers and doctors recognise the effect of psychological stress on the symptoms, but quantifying this is difficult. Psychological symptoms are more prevalent in IBS sufferers, particularly in those referred to hospital and up to 60% may fulfil diagnostic criteria for mental disorders such as depression and anxiety. Disease phobia and bodily preoccupation are also more common. Some patients describe the onset of their symptoms following an episode of gastroenteritis and there does not appear to be a major psychological component to their condition.

• endocrine changes – many women recognise that the symptoms of IBS are more marked during menstruation. No obvious hormonal correlations have been made but there are increased levels of prostaglandin E2 and F2 around this time and this may be important. Symptoms often worsen following hysterectomy which is presumably not explained by hormonal changes but may be due to damage to pelvic nerves at the time of surgery. Unfortunately, some patients undergo hysterectomy when the pain is actually caused by IBS which persists after the operation – a problem that needs to be recognised by gynaecologists.

MANAGEMENT

A thorough history is of prime importance because of the lack of a diagnostic test and broad differential diagnosis that the symptoms of IBS create. It was formerly taught that the diagnosis should be made positively and not by excluding other conditions, but some diagnoses are excluded by the history and examination and others excluded by simple tests. During the history-taking, special attention should be  given to ensure that sinister symptoms such as marked weight loss, rectal bleeding, steatorrhoea, nocturnal diarrhoea, and associated skin or joint symptoms are not present. In addition to a general examination, sigmoidoscopy should be carried out and a rectal biopsy taken, particularly in diarrhoea-predominant IBS. Blood investigations should include full blood count, biochemistry, liver function tests, and the inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). With a good history and a normal result from the above investigations, a positive diagnosis of IBS can be made, particularly in the younger age group (<40 years). It is prudent to include further colonic examination such as barium enema studies in the older age group to exclude colonic neoplasia. Over-investigation may simply serve to convince sufferers that the physician is not sureof the diagnosis and is best avoided. Occasionally, factors will confound the diagnosis such as a slightly raised CRP which will usually warrant further GI investigations but may be due to many non-GI  conditions.

TREATMENT

Successful treatment of sufferers with IBS takes considerable skill on the part of the physician. The approach taken at the time of diagnosis will have long-term effects on how patients view their condition. Careful discussion of possible mechanisms of the causes of pain and relevant trigger factors such as diet and anxiety and the universal nature of the condition will often serve to reassure sufferers.

THERAPEUTIC OPTIONS

Dietary manipulation An increase in dietary fibre has been favoured advice for years but makes as many sufferers worse as it does better. It is most useful in constipation-predominant IBS but may worsen bloating. Exclusion diets whereby various food types are removed then subsequently reintroduced into the diet until triggers are found may be beneficial in some cases but are a protracted and rather arduous treatment. Lactose intolerance may affect 10% of the population and contribute to symptoms of diarrhoea and bloating. Exclusion of dairy products from the diet is probably the easiest way to confirm this although a lactose breath test can also be used. Patients will often experiment with their diet themselves and may try unsubstantiated protocols such as low yeast diets which will usually do no harm.

Drugs

         Anticholinergics such as dicyclomine and hyoscine may help pain and diarrhoea but can have side-effects with urinary retention and effects on intraocular pressures. Antispasmodics such as mebeverine and peppermint-based products (particularly for constipation-dominant IBS) may help pain and bloating and are widely used as they do not have anticholinergic side-effects. Antidepressants have long been used in patients with severe IBS and it may be most appropriate to consider a tricyclic for diarrhoea-predominant IBS and a selective serotonin reuptake inhibitor for constipation-predominant IBS. Prokinetics may help post-prandial fullness, bloating and constipation but worsen diarrhoea-predominant IBS. If constipation does not respond to adequate bulking of the stool or an osmotic laxative then a stimulant laxative may be required. Likewise, only if diarrhoea is intractable and troublesome should constipating agents such as loperamide be used.

Complementary therapies

Hypnotherapy, stress management, psychotherapy and acupuncture have all been used and may help some sufferers.

 

III. Chronic diseases of large intestine: Ulcerative colitis

 (aetiology, diagnosis, differential diagnosis, treatment, complications).

ULCERATIVE COLITIS –

A chronic, inflammatory, and ulcerative disease arising in the colonic mucosa, characterized most often by bloody diarrhea.

Etiology and Epidemiology.

The cause of ulcerative colitis is unknown. Evidence suggests that a genetic predisposition leads to an unregulated intestinal immune response to an environmental, dietary, or infectious agent. However, no inciting antigen has been identified. The evidence for a specific microbial etiology for ulcerative colitis is even less convincing than for Crohn’s disease, and the familial tendency is less pro-nounced. Unlike in Crohn’s disease, current cigarette smoking appears to decrease risk. Like Crohn’s disease, ulcerative colitis may afflict people at any age, but the age-onset curve shows a bimodal distribution, with a major peak at ages 15 to 30 and a second smaller peak at ages 50 to 70; however, this later peak may include some cases of ischemic colitis.

Pathology.

Pathologic changes begin with degeneration of the reticulin fibers beneath the mu­cosal epithelium, occlusion of the subepithelial capillaries, and progressive infiltration of the lamina propria with plasma cells, eosinophils, lymphocytes, mast cells, and polymorphonuclear leukocytes. Crypt abscesses, epithelial necrosis, and mucosal ulceration ultimately develop. The disease usually begins in the rectosigmoid and may extend proximally, eventually involving the entire colon, or it may involve most of the large bowel at once. Ulcerative proctitis, which is localized to the rectum, is a very common and more benign form of ulcerative colitis. It is often refractory to treatment and undergoes late proximal spread in about 20 to 30% of cases.

Symptoms and Signs

Bloody diarrhea of varied intensity and duration is interspersed with asymptomatic in­tervals. Usually an attack begins insidiously, with increased urgency to defecate, mild lower abdominal cramps, and blood and mucus in the stools. However, an attack may be acute and fulminant, with sudden violent diarrhea, high fever, signs of peritonitis, and profound toxemia. Some cases develop following a documented infection (eg, amebiasis, bacillary dysentery).

When ulceration is confined to the rectosigmoid, the stool may be normal or hard and dry, but rectal discharges of mucus loaded with RBCs and WBCs accompany or occur between bowel movements. Systemic symptoms are mild or absent. If ulceration extends proximally, stools become looser and the patient may have > 10 bowel movements/day, often with severe cramps and distressing rectal tenesmus, without respite at night. The stools may be watery, may contain mucus, and frequently consist almost entirely of blood and pus. Malaise, fever, anemia, anorexia, weight loss, leukocytosis, hypoalbuminemia, and elevated ESR may be present with extensive active ulcerative colitis.

Complications

         Bleeding is the most common local complication. Another particularly severe com­plication, toxic colitis, occurs when transmural extension of ulceration results in localized ileus and peritonitis. As toxic colitis progresses, the colon loses muscular tone and begins to dilate within hours or days. Plain x-rays of the abdomen show intraluminal gas accumulated over a long, continuous, paralyzed segment of colon—a result of lost muscle tone.

         Toxic megacolon (or toxic dilation) exists when the diameter of the transverse co­lon exceeds 6 cm. The severely ill patient has a fever to 40° C (104° F), leukocytosis, ab­dominal pain, and rebound tenderness. This condition usually occurs spontaneously in the course of especially severe colitis, but some cases may be precipitated by overzealous use of narcotic or anticholinergic antidiarrheal drugs. Treatment must be given in the early stages, preferably before full-blown megacolon occurs, to avert dangerous complications (eg, perforation, generalized peritonitis, septicemia). With prompt, effective treatment, the mortality rate can be held at < 4% but may be > 40% if perforation occurs.

         Major perirectal complications, such as those in granulomatous colitis (eg, fistulas, abscesses), do not occur.

         The incidence of colon cancer is increased when the entire colon is involved and the disease lasts for > 10 yr, independent of disease activity. After 10 yr, the cancer risk in extensive colitis appears to be about 0.5 to 1%/yr. Although cancer incidence is highest in cases of universal ulcerative colitis, the risk is significantly increased with any extent of ulcerative colitis above the sigmoid. There is probably no higher absolute cancer risk among patients with childhood-onset colitis, independent of the longer duration of disease. The long-term survival after diagnosis of colitis-related cancer is about 50%, a figure comparable to that for colorectal cancer in the general population.

         Regular colonoscopic surveillance, preferably during remission, is advised for pa­tients whose disease duration (as 8 to 10 yr) and extent (beyond rectosigmoidal) place them at high risk of developing colon cancer. Endoscopic biopsies should be taken throughout the colon and reviewed by an experienced pathologist. Any grade of definite, confirmed dysplasia is a strong indication for colectomy because the likelihood of concomitant or imminent colorectal cancer may be as high as 80 %. In such cases, corrob­oratory pathologic interpretation is important to distinguish between definite neoplas- tic dysplasia and reactive or regenerative atypia secondary to inflammation. However delaying colectomy in favor of repeated follow-up surveillance is unwise if dysplasia is unequivocal. Pseudopolyps have no prognostic significance but may be difficult to distin­guish from neoplastic polyps; thus, any suspicious polyp should undergo excision biopsy.

Extracolonic problems.

Extracolonic problems include peripheral arthritis, ankylosing spondylitis, sacroiliitis, anterior uveitis, erythema nodosum, pyoderma gangrenosum, episcleritis, and in children, retarded growth and development. Peripheral arthritis, skin complications, and episcleritis often fluctuate with the colitis whereas spondylitis, sacroiliitis, and uveitis usually follow a course independent of the bowel disease. Most patients with spinal or sacroiliac involvement also have evidence of uveitis, and vice versa. These latter condi­tions may precede the colitis by many years and tend to occur more commonly in persons with the HLA-B27 antigen.

Erythema nodosum on the skin

 

 

Pyоderma gangrenosum seen in UC

 

Minor changes in liver function tests are common, but clinically apparent liver dis­ease occurs in only 3 to 5% of patients. Liver disease may manifest as fatty liver or more seriously as autoimmune hepatitis, primary sclerosing cholangitis, or cirrhosis. Primary sclerosing cholangitis (PSC) occurs in 5% of ulcerative colitis patients, most commonly in those who were young when the colitis began. PSC may precede symptomatic ulcerative colitis by many years and is mort reliably diagnosed by endoscopic retrograd-cholangiography than by liver biopsy. Some investigators believe that signs of subclinics ulcerative colitis, if systematically sought, could be found in all patients with PSC. A late complication of ulcerative colitis-associated PSC is cancer of the biliary tract which may appear even 20 yr after colectomy. More than 50% of PSC and cholangiocarcinoma cases in Western countries occur in patients with Crohn’s disease or ulcerative colitis.

Diagnosis

         The history and stool examination permit a presumptive diagnosis of ulcerative colitis that should always be confirmed by sigmoidoscopy, which provides a direct, immediate indication of disease activity. Total colonoscopy is not usually necessary before treatment and may be hazardous in active stages because  of the  risk  of perforation. In early cases, the mucous membrane is finely granular and friable, with loss of the normal vascular pattern and often with scattered hemorrhagic areas; minimal trauma (friability) causes bleeding in multiple pinpoint spots.

 

VIDEO 3 (Colonoscopy. Ulcerative colitis)

         The endoscopic spectrum of ulcerative colitis includes (a) mucosal edema, erythema, loss of vasculature; (b) granular mucosa with pinpoint ulceration and friability; (c) regenerated (i.e., healed) mucosa with distorted mucosal vasculature; and (d) regenerated mucosa with typical postinflammatory pseudopolyps

 

         The mucosa soon breaks down into a red, spongy surface dotted with many tiny blood- and pus-oozing ulcers. As the mucosa becomes progressively involved, the inflam­mation and hemorrhage extend into the bowel muscle. Large mucosal ulcers with copious purulent exudate characterize severe disease. Islands of relatively normal or hyperplastic inflammatory mucosa (pseudo-polyps) project above areas of ulcerated mucosa. Biopsies may be nonspecific and sometimes cannot exclude acute infectious (self-limited) colitis; however, features that suggest chronicity (eg, distorted crypt architecture, crypt atrophy, a chronic inflammatory infiltrate) support the diagnosis of ulcerative colitis. Even during asymptomatic intervals, the sigmoidoscopic appearance is rarely normal; some degree of friability or granularity almost always persists. There is loss of the normal vascular pattern, and bi­opsy shows evidence of chronic inflammation.

         Plain x-rays of the abdomen sometimes help to judge the severity and proximal ex­tent of the colitis by showing loss of haustration, mucosal edema, and absence of formed stool in the diseased bowel. Barium enema, like colonoscopy, is not usually necessary before treatment and may be hazardous in active stages because of risk of perforation. Later in the course of disease, however, the entire colon should be evaluated to deter­mine the extent of involvement. Total colonoscopy is the most sensitive and widely used method, although barium enema can be informative. Barium studies show loss of haustration, mucosal edema, minute serrations, or gross ulcerations in severe cases. A shortened, rigid colon with an atrophic or pseudopolypoid mucosa is often seen after several years’ duration.              

         Colonoscopy with biopsy is mandatory to evaluate the nature of a stricture. Biopsy may also help distinguish ulcerative colitis from Crohn’s disease if the inflammation is highly focal or if a granuloma is seen.

Prognosis

         Usually, ulcerative colitis is chronic with repeated exacerbations and remissions. A rapidly progressive initial attack becomes fulminant iearly 10% of patients, with complications of massive hemorrhage, perforation, or sepsis and toxemia. Complete recovery after a single attack may occur in another 10%; however, there always remains the possibility of an undetected specific pathogen.

         Nearly 1/3 of patients with extensive ulcerative colitis require surgery. Total proc­tocolectomy is curative: Life expectancy and quality of life are restored to normal, and the risk of colon cancer is eliminated.

         Patients with localized ulcerative proctitis have the best prognosis. Severe systemic manifestations, toxic complications, and malignant degeneration are unlikely, and late extension of the disease occurs in only about 20 to 30%. Surgery is rarely required, and life expectancy is normal. The symptoms, however, may prove exceptionally stubborn and refractory. Moreover, because extensive ulcerative colitis may begin in the rectum and spread proximally, localized proctitis should not be definitively diagnosed until it has stayed localized for > 6 monthes. Localized disease that later extends is often more severe and more refractory to therapy.

Treatment

       Avoiding raw fruits and vegetables limits mechanical trauma to the inflamed colonic mucosa and may lessen symptoms. A milk-free diet may help but need not be continued if no benefit is noted. An anticholinergic drug or loperamide 2.0 mg or diphenoxylate 2.5 mg orally 2 times a day to 4 times a day is indicated for relatively mild diarrhea; higher oral doses of loperamide (4 mg in the morning and 2 mg after each bowel movement) or diphenoxylate (б mg 3 times a day or 4 times a day), deodorized opium tincture 0.5 to 0.75 mL (10 to 15 drops) every 4 to 6 hours, or codeine 15 to 30 mg every 4 to 6 hours may be required for more intense diarrhea. These antidiarrheal drugs must be used with extreme caution in more severe cases because they may precipitate toxic dilation.

       In mild or moderate disease that does not extend proximally beyond the splenic flex­ure, remission may sometimes be achieved with a hydrocortisone enema instead of with oral corticosteroid therapy. Initially, hydrocortisone 100 mg in 60 mL of isotonic solution is given rectally once or twice/day. It should be retained in the bowel as long as possible; instillation at night, with the patient’s hips elevated, may prolong retention and extend distribution. Treatment, if effective, should be continued daily for about 1 wk, then every other day for 1 to 2 wk, then discontinued gradually over 1 to 2 wk. Because systemic side effects may occur as with oral corticosteroids, enema preparations of new corticosteroid analogs such as budesonide, which is topically potent but less systemically active, are becoming more widely used outside the USA.

         Mesalamine may also be given by enema and is beneficial in many cases of refractory proctosigmoiditis and left-sided colitis. The standard dose is mesalamine 4 g in 60 or 10 mL of solution giveightly, although recent studies suggest that 1 g may be equally effective. Suppositories of mesalamine 500 mg are also effective in treating proctitis, or ever proctosigmoiditis, and are preferred by patients. After clinical and endoscopic remission has been established (usually within a few weeks), frequency of administration car be tapered, although a topical or oral long–term maintenance regimen is often required to prevent relapse.

         More extensive mild or moderate disease as well as localized disease may respond to oral sulfasalazine. Because GI intolerance common, the drug should be given with food and, if necessary, in the enteric-coated form. To minimize common side effects (eg, nausea, dyspepsia, headache), dosage should initially be low (eg, 0.5 g orally 2 times a day) and gradually increased over several days to 3 to 6 g/day in divided doses. Reversible de­creases in sperm count and motility may occur in up to 80% of men. More serious side effects (eg, blood dyscrasias; hemolytic anemia; paradoxical exacerbation of colitis, rarely, hepatitis) may prevent use of sulfasalazine.

         Once remission is achieved, long-tem maintenance therapy with sulfasalazine 1 to 3 g/day is indicated to prevent relapse. The sulfapyridine component of sulfasalazine; interferes with folic acid absorption, so folate supplementation of 1 to 2 mg /day is generally recommended. Patients with chronic fecal blood loss may also require iron to prevent anemia. New oral analogs of sulfasalazine have been developed to eliminate the sulfapyridine moiety, which is responsible most of the common side effects, while allowing delivery of mesalamine to diseased reas of the small intestine and colon. Clinical trials have shown that olsalazine, a mesalamine dimer, is effective in treating mild-to-moderate colitis and maintaining remission. Like sulfasalazine, olsalazine depends on an azo- bond to prevent рrоxymal absorption of the mesalamine and to keep іt in the intestinal lumen until the azo- bond hydrolyzed and active mesalamine геleased by the enzymatic action of bacterial flora in the lower ileum and colon. Bacterial cleavage of the compound releases twice quantity of mesalamine without any sulfonamide. Another mesalamine-based azo compound, balsalazide, has also proven effective and has been approved in many countries.

Moderately severe disease in ambulatory patients usually requires systemic cortico­steroid therapy. Relatively intensive therapy with oral prednisone 40 to 60 mg/day in either single or divided doses frequently induces dramatic remission. After 1 to 2 wk, the daily dose may be gradually reduced by about 5 to 10 mg/wk. Sulfasalazine (2 to 4 g/ day in divided doses) may be added when prednisone 20 mg/day is controlling the colitis; very gradual tapering and ultimate withdrawal of the corticosteroid may then be possible.

Severe disease, manifested by > 10 bloody bowel movements per day, tachycardia, high fever, or severe abdominal pain, requires hospitalization. If the patient had been re­ceiving corticosteroid treatment > 30 days at the time of admission, hydrocortisone 300 mg/day should be given by continuous I/V drip. In patients who have not received recent corticosteroids, ACTH 75 to 120 U/day by continuous i/v drip has been reported to be a slightly more effective initial therapy, but adrenal hemorrhage is occasionally a complication. In either event, treatment is given for 7 to 10 days while the response is monitored by recording the nature and frequency of bowel movements. An initial ab­dominal x-ray should be obtained to assess the extent and severity of colonic involve­ment, and the patient must be observed closely for the development of toxic mega­colon.

       Unless dehydration resulting from diarrheal losses is imminent, use of hydrocorti­sone or ACTH in I/V 0.9% sodium chloride solution is not usually advised because edema is a frequent complication. Potassium chloride 20 to 40 mEq/L added to the I/V fluids usually helps prevent hypokalemia. Anemia may require transfusions. Parenteral hyper­alimentation is sometimes used for nutri­tional support but is of no value as primary therapy; in fact, patients who can tolerate food will do better if they eat.

Oral prednisone 60 mg/day may be substituted after remission has been achieved with the 7- to 10-day course of parenteral treatment. A patient who remains well on the oral regimen for 3 to 4 days may leave the hospital, and the corticosteroid dosage may be gradually reduced at home under close medical supervision.

Immunomodulatory drugs.

Immunomodulatory drugs are acceptable for some patients with refractory or corticosteroid-dependent ulcerative colitis. Azathioprine and 6-mercaptopurine inhibit T-cell function, and a decline in the activity of both natural killer cells and cytotoxic T cells is correlated with a clinical response. The full benefit of azathioprine 2 to 3.5 mg/ kg/day or 6-mercaptopurine 1.5 to 2.5 mg/ kg /day may not be seen for 3 to 6 monthes because these drugs are slow-acting. Complications include pancreatitis (an absolute contrain­dication to continued use) and reversible neutropenia, which simply requires a lower dose with regular monitoring of WBC counts.

Cyclosporine has a rapid onset and is primarily indicated for acute severe ulcerative colitis unresponsive to high-dose IV corticosteroids. Continuous W infusion of cyclo­sporine can induce remission and avert surgery in about 80% of such cases. An additional 6 mo of treatment with oral cyclosporine, ultimately shifting to azathioprine or 6-mercaptopurine, may sustain longer-term remissions in 50 to 60% of cases. Because serious and even fatal complications (eg, renal toxicity, seizures, opportunistic infections) may occur, patients generally are not offered cyclosporine unless the safer curative option of colectomy is infeasible or inappropriate. Candidates for cyclosporine therapy should be referred to centers experienced in its use.

 

The scheme of Case History.

 

 

Sequence of interviewing.

The Case History consist of such components as: the identifying data, the main complaints, the history of present illness, the past medical history, the review of systems. The outlined compounds of a case history, being used in the correct order, help to obtain the organized set of data about patient’s condition and disease.

 

Identifying Data and their diagnostic value

Identifying Data include at least age, sex, race, place of birth, present address, marital status, occupation (profession).

 

Patient¢s complaints and their detalization

You should collect main patient’s complaints, when possible, in patient’s own words, and then describe their characteristics. The principal symptoms should be described in terms of their location, quality, quantity or severity, timing (i.e., onset, duration, and frequency), setting, factors that have aggravated or relived these symptoms, and associated manifestations. Then find out and analyze the general complaints. For example, weakness, high body temperature, etc. 

The chief complaint represents the specific reason for the patient’s visit to the clinic, office, or hospital. The chief complaint may be viewed as the theme, with the present illness as the setting of this problem. Six guidelines determine appropriate recording of the chief complaint: (1) it consists of a brief statement, (2) it is restricted to one or two symptoms, (3) it refers to a concrete complaint, (4) it is recorded in the patient’s or parent’s own words, (5) it avoids the use of diagnostic terms or translations, and (6) it states the duration of the symptoms.

The doctor elicits the chief complaint by asking open-ended neutral questions such as, “Tell me what seems to be the matter?”, “How may I help you?” or “What brings you here?”  Labeling-type questions such as, “How are you sick?” should be avoided, since it is possible that the reason for the visit is not because of illness. For example, the visit may be for a routine health assessment, or the chief complaint may be of a nonphysical nature.

Examples of properly recorded chief complaints for a variety of situations may be: (1) ambulatory clinic – “My patient has had a runny nose and sore throat for 4 days, but today it is worse”, (2) hospital admission – “I need to have my tonsils fixed”, sore throat and repeated earaches for 5 years, and (3) health center – “We are here for a routine checkup”, last visit 1 year ago.

If the visit is for  examination, one can ask, “Before we begin, is there anything of particular concern that you would like to discuss?”. This type of statement encourages the parent (or patient) to bring up an issue that may not surface during routine interviewing.

Occasionally it is difficult to isolate one symptom or problem as the chief complaint because the parent may identify many. In this situation it is important to be as specific as possible when asking questions. For example, asking informants to state which one problem or symptom caused them to seek help now may help them to focus on the most immediate concern.

 

 

Patient’s present illness history

The history of present illness is a clear,  chronological narrative  account  of the problems which the patient is seeking care for. It should include the onset of the problem, the setting in which they was developed, their manifestations,  treatment, their impact upon the patient’s life, and meaning to the patient. Relevant data from the patient’s chart, such as laboratory reports, also belong in the present illness.

The history of the present illness is a narrative of the chief complaint from its earliest onset through its progression to the present. Its four major components are (1) details of onset, (2) complete interval history, (3) present status, and (4) reason for seeking help now. The focus of the present illness is on all those factors that are relevant to the main problem, even if they have disappeared or changed during the onset, interval, and present.

Analyzing a symptom. Since pain is often the most characteristic symptom denoting onset of a physical problem, it is used as a prototype for analysis of a symptom. The doctor should assess pain for (1) type, (2) location, (3) severity, (4) duration, and (5) influencing factors. The type or character of pain should be as specific as possible.

By type  pain may be sharp, throbbing, dull, aching, stabbing, and so on. Whatever words they use should be recorded in quotes.

The location of the pain also must be specific. “Stomach pains” is too general description. Sometimes it is necessary to ask to “point with one finger to where it hurts”. The doctor can also determine if the pain radiates by asking, “Does the pain stay there or move? Show me where it goes with your finger“.

The severity of pain is best determined by finding out how it affects the patient’s usual behavior. It is preferable to record pain in terms of interference with activity.

Duration of pain should include the duration, onset, and frequency of attacks. Influencing factors are anything that causes a change in the type, location, severity, or duration of the pain. These include (1) precipitating factors (those that cause or increase the pain), (2) relieving factors (those that lessen the pain, such as medications), (3) temporal events (times when the pain is relieved or increased), (4) positional events (standing, sitting, lying down, and so on), and (5) associated events (meals, stress, coughing, and so on).

A standard method of analyzing a symptom is listed in the following outline. These three categories – onset, characteristics, and course since onset – comprise the essential data for the present illness. Although the analysis of a symptom has concentrated on discussion of physical complaints, the same process of description and investigation can be used for emotional or psychosocial problems.

 

Analysis of a symptom

                   I.      Onset

a)          Date of onset,

b)         Manner of onset (gradual or sudden),

c)          Precipitating and predisposing factors related to onset (emotional disturbance, physical exertion, fatigue, bodily function, pregnancy, environment, injury, infection, toxins and allergens, therapeutic agents, and so on).

               II.       Characteristics

a)            Character (quality, quantity, consistency, or others),

b)           Location and radiation (of pain),

c)            Intensity or severity,

d)           Timing (continuous or intermittent, duration of each, temporal relationship to other events),

e)            Aggravating and relieving factors,

f)             Associated symptoms.

III. Course since onset

a)           Incidence

·          Single acute attack.

·          Recurrent acute attacks.

·          Daily occurrences.

·          Periodic occurrences.

·          Continuous chronic episode.

b)           Progress (better, worse, unchanged),

c)           Effect of therapy.

 

Past history:

The general state of health:

Previous diseases including viral hepatitis, sexual-transmitted diseases, infectious diseases within the last month, AIDS-risk factors

2. Immunizations: tetanus, diphtheria, polio etc.

3. Adult illness, operations, injuries, allergies.

4. Current medications, including home remedies, nonprescription drugs, and medicines borrowed from family or friends. When patient seems likely to be taking one or more medications, survey one 24-hour period in detail.

5. Diet.

6. Sleep Patterns. Including times that the person goes to bed and awakens, difficulties in failing asleep or staying asleep, and daytime naps.

7. Habits, including exercise and the usage of coffee, alcohol, other drugs, and tobacco.

8. The Family History:

The age and health, or age and cause  of death of each immediate family member (i.e., parents, siblings, and patients). Data on grandparents or grandchildren may also be useful.

The occurrence in the family of any of the following conditions: diabetes, tuberculosis, heart disease,  high blood pressure, kidney disease, cancer, arthitis, anemia, headaches, mental illness, or symptoms like those of the patient.

Social History: assessment of the home and job environment, professional hazards.

  Review of Systems: the relevant items are limited, but expand as the patient’s age increases.

 Systems ‘reviewing:

Carrying out the reviewing of systems you should pay attention to the following:

  1. General state of health: weight, recent weight change, weakness, fatigue, fever.

2. Skin: Rashes, lumps, itching, dryness, color changes, changes in hair or nails.

3. Head: Headache, head injury.

4. Eyes: Vision, glasses or contact lenses, last eye examination, pain, redness, excessive tearing, double vision, glaucoma, cataracts.

5. Ears: Hearing, tinnitus, vertigo, earaches, infection, discharge.

6. Nose and sinuses. Frequent colds, nasal stuffiness,   hay  fever, noseblends, sinus trouble.

7.  Mouth and throat. Condition of teeth,  last  dental  examination, sore tongue, frequent sore throats.

8. Neck: Lumps ieck swollen glands, pain in the neck.

9. Breasts: Lumps, pain, nipple discharge, self-examination

10. Respiratory system: Cough, sputum (color, quantity), hemoptysis, wheezing, asthma, bronchitis, emphysema, pneumonia, tuberculosis, pleurisy, tuberculin test; last chest x-ray film.

11. Cardiovascular system: high blood pressure, rheumatic fever, heart murmurs; dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema; chest pain, palpitations; past electrocardiogram or other heart tests

         12. Gastrointestinal system: Appetite, nausea, vomiting, vomiting of blood, indigestion, frequency of bowel movements, change in bowel habits, rectal bleeding or black tarry stools, constipation, diarrhea; abdominal pain, food intolerance, meteorism, hemorrhoids; jaundice, liver or gallbladder trouble, hepatitis.

13. Urinary: Frequency of urination, polyuria, nocturia, dysuria, hematuria, urgency, hesitancy, incontinence; urinary infections, stones.

14. Genito-reproductive:

Male: Discharges, history of venereal disease and its treatment, hernias, testicular pain; sexual difficulties.

Female: Age at menarche; regularity, frequency, and duration of periods; amount of bleeding, bleeding between periods or after intercourse, last menstrual period; dysmenorrhea; age of menopause, menopausal symptoms, post-menopausal bleeding. Discharge, venereal disease and its treatment; Number of pregnancies, number of abortions (spontaneous and induced);complications of pregnancy; sexual difficulties.

15. Musculoskeletal system: Joint pains or stiffness, arthritis, backache..Muscle pain.

16. Periferal vessels: Intermittent claudication, cramps, varicose veins, thrombophlebitis.

17. Nervous system: Fainting, blackouts, paralysis, local weakness, tremors, memory.

18. Endocrine system: Thyroid trouble, heat or cold intolerance, excessive sweating, diabetes, excessive thirst, hunger, urination.

19. Hematologic: Anemia, easy bruising or bleeding, past transfusions and possible reactions and antibiotics.

 

A Scheme of Inquiry Questioning a patient (Interrogatio)  General information about a patient (Praefatio) Name, surname Sex Age Permanent address Occupation Place of employment The name of referral institution Date of admission to the hospital Date of discharge from  the hospital Patient’s complaints (Molestia aeqroti, Querellae aeqroti) The main complaints are the main patient’s problems which he is suffered for. Every complaint should be defined with determination of its location, quality, quantity, severity, timing (onset, duration, frequency), the setting in which they occur, factors that have aggravated or relieved them, associated manifestations, any changes of these characteristics in dynamics, appearance of new symptoms. Full description of complaints should be noted once for do not appaering need of searching different detalis in other parts of the Case History. A curator describes complaints of every system and details them concerning  main suffering system(s). Then a curator describes in detalis the secondary complaints. To define them is possible only when a doctor asks patients additional questions because these complaints are not so severe. Review of systems (Status praesens subjectivus) Cardio-vascular system Does the patient feel pain  in the heart region? If yes, you should define the following characteristics:            –location (behind the sternum, above the apex, over the whole heart area);            –when does it develop (on physical exertion, emotional overstrain, at rest);                    –its irradiation (to the left arm, neck, left part of the neck, low jaw, intercapular space, left shoulder-blade);            -characteristics of pain (acute, dull, constricting, stabbing, burning, pressing, boring, arching, or  a sense of heaviness); –intensity (slight, of moderate intensity, strong, severe);            –timing (persistent, periodical), if periodical – the frequency of its appearance  a day;            –duration (during some minutes, hours, days);              -associated manifestations ;            -provoking factors (physical or emotional overstrain);            –factors that relieve or remove  pain; -patient’s behavior during pain attack,body position that relieves pain. Palpitation. If yes, what are its:            –frequency (constant, paroxismal);            -if periodical – duration of an attack, in what time and under what conditions does the attack develop: at physical overload, emotional overstrain, at rest, due to change in posture, without any  reason; -when does it disappear?            Is it followed by heart intermissions (a sense of  heart arrest,  heart disposition)? If yes-      what is the reason of these unpleasant feelings on the patient’s own opinion?      Frequency of attacks a day, their duration, factors that relieve or remove the symptom.   Feeling of pulsations in different parts of patient’s body: its -location, frequency, duration; -relation to palpitation, heart intermissions, pain; -provoking factors; –factors that relieve or remove  symptom.   Does the patient complain of dyspnea? If yes, what is            -the setting of its development (on exertion, during conversation, emotional overstrain, at rest)?            -Its type (expiratory,  inspiratory or mixed);            -is it attack-like or constant?            -Is it more intensive in recumbent or upright position of the patient? -Relation of dyspnea to body position (upright, recumbent), physical loading.     Suffocation: if present, define its            –time of appearance (in day-time, at night);            -frequency of attacks;            -duration;            -factors, that relieve the symptom;            -what time and under what conditions does it develop (on exertion, emotional exertion, at night)?   Cough: time and condition of its appearance (in the morning, in the evening, at night);            –timing (is it permanent or periodical), in the last case – duration and frequency of attacks;            -loudness and intensity of cough (inssiculation, slight, of moderate intensity, loud);            –character of cough (dry or with expectoration of sputum (moist);            -under the what conditions does cough develop or become more severe, its relations to respiration, physical loading, singing, conversation etc.); -factors that relieve or remove cough.   If cough is moist, define amount of sputum discharged per day and in one split;            –peculiarities of discharging (is it heavy or easy, at what day time and in what body position sputum may be best discharged);            -colour of sputum (greish, reddish);            -smell of sputum;            -are there any admixtures of blood in sputum, if yes, what is the degree of bleeding (blood streaks in sputum, sputum mixed with blood, pure blood in several splits, pronounced bleeding). Colour of  sputum should be clarified (light-red, dark), frequency of bleedings, duration, provoking factors, under the what conditions does bleeding become less intense  or disappear.   Edema: if present, what is its location?            –time of appearance (in the morning, in the evening, all time);            -under the what conditiond does in develip or become more pronounced (physical loading etc.)?            –Factors, that relieve the symptom (due to usage of diuretics or on its own).            -Relation of edema to water and salt intake. Claudicatio intermittens: the time of appearance, relieving factors. The signs of spasm of perypheral arteries: pain in the limbs, feeling of “freezing”, “numbness” of fingers, feeling of “dead” finger, headache, flickering before eyes.   Respiratory system Does the patient breathe through the nostrils freely  or have any  difficulty in breathing ? Dryness in the throat or behind the sternum (indicate, if present). Does he (she) feel pain  in the chest, if yes, desribe, please, its location (with indication of topographic zones and lines); -irradiation (toward which zone);            –characteristic (acute, dull, stabbing, arching, pressing, boring, stretching, gnawing);            –intensity (slight, of moderate intensity, strong, severe);            –timing (constant, paroxismal)? In the last case – time of appearance;            –provoking factors, especially the relation of pain to breathing movements, coughing, changes of body position;            -factors that relieve or remove pain.   If patient complains of cough, you should determine its            -time and condition of appearance (in the morning, in the evening, at night);            -timing (is it persistent or fitlike), in the last case – duration and frequency of attacks;            -loudness and tembre of cough (weak, of moderate loudness, loud, barking, loudless);            -hacking cough (inssiculation);            –character of cough (dry or with expectoration of sputum (moist).   If cough is moist, define: volume of sputum discharged per day and in one split;            –peculiarities of discharging (is it heavy or easy, at what day time and in what body position is sputum discharged);            -colour of sputum (greyish, yellowish, greenish, reddish);            -does it smell of putridity?            -Are there any admixtures of blood in sputum, if yes, what is the degree of bleeding (blood streaks in sputum, sputum mixed with blood, pure blood in several splits, pronounced bleeding);            -colour of blood in sputum (light-red, dark, with raspberry hue, rusty).   Dyspnea: if present, define  following:            -setting of its appearance (at rest or on exertion, degree of loading which conducts dyspnea);            -is it permanent or periodical, in the last case – duration of attacks;            -type of dyspnea (expiratory,  inspiratory or mixed);            –provoking factors (smells, emotional strain, overcooling, physical exertion).   Suffocation; if present, define the following points:            -aura: have been the patient ever noticed any previous symptomes like itching, dyspnea, nasal catarrh, sneezing or other before the attack?            -When does the attack  occur?            -Patient’s behavior and posture during the attack?            –Duration, frequency, intensity  of attacks;            -relieving factors (if the patient feels better after usage of medicines –  define the form of  usage: inhalations or injections).   Digestive system What is patient’s appetite (good, moderate, increased, lack of appetite,  supressed, deranged, distaste for some kind of food (indicate it), fear of food intake). Saturation: moderate, quick, permanent, constant feeling of hunger. Mastication: deranged or preserved, pain at mastication (yes, no). Does the patient complain of thirst? If yes, indicate its timing (constant or intermittent), when does it occure, relieving factors. The volume of water drunk per day.  Salivation: its periodicity (permament or periodical), duration, when does it occure, relation to food intake, relieving factors. Dryness in the mouth, pain and burning sensation in the tongue (yes, no). Taste in the mouth:   normal, sour, bitter, metallic, sweet, deranged, perverted. Swallowing and passage of food portion through the esophagus (painful, impossible or  difficult (does the difficulty depend on the sort of food – solid, liquid)?   Does the patient complain of pain in abdominal region? If yes, define its            -location;            -under which conditions does it appear?            -Relation to the time of food intake (immediatelly after eating, in some minutes, 20-30 min, 40-50 min, in some hours,  “fasting” and “night” pain);            -to the sort of food (fat, fried, spicy, milk, coarse, sweet) and its amount; -characteristics of pain: acute, knife-like, dull, burning, boring, girdle, feeling of heaviness in the certain abdominal zone);            -its intensity (slight, of moderate intensity, strong, severe);            -irradiation;            -time relationship (permament, periodical, undulate, seasonal);            -duration of attacks (during some minutes, hours, days);            -under what conditions does pain develop or become more intensive?            –Relieving factors (vomiting, food intake, medications, intake of soda, applying of heat or  cold). In which body position does pain decrease?            -Associated manifestations (changes of skin colour, urine, feces etc.).   Nausea: if present, detail the following:            -does it preceed vomiting or not?            -Is there any relation of nausea occurence to food intake (yes, no) and the sort of food (if yes, indicate the sort of food)?   If the patient complains of vomiting it is necessary to define the following:            -time of its appearance (on the empty stomach, relation to  food intake: immediately after or late). Frequency of occurence, relation to pain;            -provoking factors; relation to food intake, to the sort of food, relieving factors, does vomiting relieve patient’s condition?            -Volume and character of emesis (with digested or indigested food, as a coffee ground, with admixtures of fresh blood, bile, mucus, foamy);            -smell of the vomit if any (ammonia, bitter oil, acid, putrid, fecal, without any smell);            -does vomiting relieve patient’s condition?   Regurgitation: if the patient suffers for, define the following:            -time of its appearance (immediately after meals, some time after meals, after change of body position, on straining effort etc.);            -character of regurgitation (gaseous, food, bitter or acid belching, musty smelling);            -its duration, intensity, relieving factors.   In the case of heartburn define the frequency of its attacks,             -relation to food intake and the sort of food (immediately afer meals, after change of a position of the body);            -relieving factors (taking baking soda, water, any drugs etc.).   Meteorisms: (present or absent);            -does the patient feel abdominal murmur, fluctuation? If yes,  indicate  their location, under what conditions they develop or become more intensive, relation to food intake (indicate the sort of food) and to pain. Relieving factors;            -passage of gasses through the intestine: free, difficult or impossible. Their smell (sharp, putrefied, acid). Relation to food intake, the kind of food and defecation.   Stool: define the following:            –frequency of  defecation (frequent, regular, irregular, constipation, after enema);            -a feeling of incomplete emptying of the bowels after defecation;            –volume and consistence of stool (formed, fragmentation, semiliquid, ribbon shaped, watery, rie-water);            -сolour (brown, light, tarry)  and smell of feces;            –admixtures if any (mucus, blood, pus, helminths, indigested food, foreign bodies);            -in the case of blood discharging –does it occur during or after defecation; are feces mixed with blood or blood is present on the surface of feces;            -tenesmus if any.     Itching, anal pains if any: timing, duration, intensity, relation to defecation.   Urinary system Pain in the lumbar region: its  character (dull, aching, acute, colicky);            -is it permanent or attack-like?            -Its irradiation, duration;            –provoking and relieving factors.   Urination: define the following:            -is urination normal or painful?            -Frequency of urinations per day (general and separately during day- and  night-time);            –the volume of water taken per day and discharged urina per day; correlation between daily and night diureses;            -colour of urine (straw-yellow, “meat wastes”, “beer”);            -smell  of urine;            -urine sediment (present or absent, colour of sediments).            Urinary incontinence if any: is it permanent or periodical, in the last case- its provoking factors (laughing,  coughing, drinking water etc.).   Endocrine system Ask patient about the following: Impairment from normal body growth and (or) fortmation of body build. Any changes of body weight during last years, months (obesity, weight gain or loss, cachexia). Ask about presence of the following signs: permanent thirst, hunger, dryness in the mouth, frequent urination, profuse urination, skin itching, white discharge, irritability, teafulness, palpitation, tremor of hands, inhibition. Impairment of initial and secondary sexual signs. Has the  patient ever noticed any changes of skin (profuse swetting or dryness, red skars, purulent rash of thre skin, “tanny” skin)? Hair growth pattern:  pathological, excessive, baldness (indicate if any). Female should be asked about first menstrual period, the duration and regularity of mensrual period, bleeding between periods or during menopause, menstrual cycle disorders, subjective senses associated with menopause (headache, depression, hot flashes). Absence of menses, sterility if any. Evaluation of libido.   Musculo-skeletal apparatus  Pain in joints, bones, muskces: yes, no. If yes, define the following:            -location; “wandering” pain if any;            -timing, duration of pain, its intensity;            -under what conditions does it develop or  aggravate: motion, depending on meterological factors etc.;            -relieving factors;            -pain in the backbone at motions (in which zones)?            -Have the patient ever beeoticed puffiness of joints or changes of their configuration, any deformations? Changes of skin above joints (reddness, glitter, tension, local rising of skin temperature (indicate the afflicted joint)?            –Is the patient satisfyed with volume of movements in upper, lower limbs?            -Joint and vertebral columne stiffness (location, duration, under what conditions does it develop  or aggravate, when does it disappear).   Nervous system and sensory organs Does the patient feel headache? If yes, define the character, location, intensity, timing, duration of headache. What factors do relieve or remove  it? Dizziness: when does it occure, its duration, timing, frequency, intensity. Sleep: its deepness, duration, character of dreams (normal, deep, insomnia). Does the patient sleep well? Any unususal, expressive dreams. Work capacity: preserved or  reduced. Mood: its changes, excessive erritability, tearfulness, apathy, peculiarities of behavior and  speech. Convulsions, muscular tremor, dizziness, loosing of consciousness (indicate if present). Feeling of weakness in limbs. Deranged sensitivity (parestesias and the like), disorders of gait. Disorders of sense organs: changes of vision, hearing, smell, taste, desire to eat inedible substances. Noise in the ears if any.   Blood system Pain in bones (indicate its location),  in the right or left hypochondrium: when does it occur, its character, time relationship, duration, intensity, provoking and relieving factors. Bleeding, hemorrhagic rash on the skin and mucous membranes (their location, character, frequency of occurence, duration). Provoking and relieving factors. Enlargement of perypheric lymph nodes if any: (their location, consistency, painfulness). Condition of skin and mucous membranes (itching, pain, change of colour, necrotization). Enlargement of the abdomen in the projection of liver and spleen.   General complaints (molestia communis): rise of body temperature (indicate the time and limits of its fluctuation during a day, relieving factors); character of fever and its duration. Chills and their frequency. Sweating: its intensity and time of occurence (night sweating). General indisposition, weakness, fatigue, decreasing of work capacity, other complaints.   History of present illness (Anamnesis morbi) When and  under the what conditions did the first signs of the disease appeare? What was the beginning (onset) of the disease (acute, gradual)  What were the first signs of the disease? What is the main cause of the disease on the patient’s own opinion? What preceded the disease (overcooling, infection, stress, physical examination or other factors)? Did the first symptoms change in dynamics? Did new symptoms occur from the beginning of the disease till the moment of admission? (rising, aggravation, releising or removing of new symptoms should be described in chronologic sequence). Did the patient receive any treatment before the admission to the hospital? If yes, what was it (self-treatment, ambulatory or long-standing hospital treatment)? What kind of medicines or another therapeutical agents did the patient receive? What was the result of previous treatment (did the patient feel him better, worse or without any  changes)? Have the patient been ever examined before present admission to the hospital? If yes, what are the results of examination? In the case of chronic disease following should be detalized: the first attack of the disease (its detail describtion – onset, duration, severity etc), course (frequency, duration of exacerbations, results of their treatment, patient’s self-being after treatment and during remissions),  diagnosis, that was made at previous examinations. The last exacerbation should be described literally. Data about course of the disease during present treatment in the hospital should be recorded too (till the moment of the beginning of curation). Patient’s work-status (medical insurance) before the hospitalization is than clarified as well as  reasons of hospitalization. Dynamics of symptoms after present admitting till the moment of examination is given.    Patient’s life history (Anamnesis vitae) The main data about patient’s life should be presented in a short form. Physical and phsychomotor development of the patient in childhood. Progress in studing process at school: what were the skills in theoretical subjects and physical training (excellent, good, bad), the interest for education and contact with school friends, hobby). The beginning of work activity and following professional way (which professions was the patient dealt with and how long, the kind of activity (physical, mental), labor conditions, probably harmful professional factors). Present labor conditions: strong noise, vibrations, high ambient temperature, draftes, moistness, character of illumination, cold (work in the open), some chemical and radiation agents. The mode of work activity: duration of work, breaks, holidays, leave. Are there any tensions at work? If any professional disease is suspicted professional anamnesis should be taken more detaily (see appendix 2). Material and housing conditions in different periods of patient’s life and nowadays: what is the area of house (flat), which floor does the flat occupy, character of heating, moistness, draftes. Composition of family, family budget, any tensions in the family. How does the patient   spend his leisure time: is it enough time for sleep, rest, walks in the open. Gardening, sport (what kind of sports and exercises does he go in for). Nutritional mode: regular or irregular feeding, frequency of meals, does the patient eat in the housing conditions or out of home. The character of meals, nutritional habits,  dry meals. Harmful habits: smoking – if yes, indicate, in which age did the patient start to smoke, the quantity of  sigarettes smoked per day, smoking on empty stomach and at night; –            alkohol consumption – if yes, ask about the following: in which age did the patient start to drink alkohol, how often and how much does he drink, the sort of drink, how does the patient tolerate alkohol; –            coffeiemania – does the patient drink coffee, if yes – how often and in which day time; –             drug abuse, toxicomania. Any diseases, traumas, contusions, wounds in the past – if yes, enumerate all of them in chronological sequence with indication of the following: in which patient’s age did the mentioned above conditions take place, their duration, severity, complications; treatment should be indicated as well. Special attention should be paid to infectious diseases (thyphus, hepatitis etc.) as well as to veneral diseases, AIDS, tuberculosis in the patient and his relatives. AIDS-risk factors: residence in  endemic regions, multiple sexual relations and perversions, repeated hemotransfusions, operations. If  there is suspicion on infectious disease – infectious anamnesis should be taken more detaily (see appendix 3).  Family anamnesis: In female patient it should include the following information:   –when did the first menstruation (menarche) take place, character of menses (regularity, duration, volume of discharged blood). The age of marriage and beginning of sexual life. Number of  pregnancies and  their results: abortions, inevitable abortions (in which reason), miscarried fetus, delivery, premature birth, jaundice of newborns;   -breach of menstrual function: painful, premature, delayed, protracted, excessive menstruations, bloody discharges between menstruations. Inflammation of female reproductive system organs;   -if menstruation had disappearted (climax), it should be recorded in which patient’s age did it take place, were (are) there any unpleasant feelings during climax (headache, reddening of the face, irritability etc.). In male patients in should be indicated the following information: breach of descent of testes (monirchodoism, cryptorchism), inflammatory diseases  of testes, prostate; sexual problems. Allergological anamnesis: Allergic reactions (urticaria, Quincke’s edema, anaphylactic shock etc.) to different kind of food, medicines, industrial or domestic allergens, trees’ blooming, feather etc.  Allergic diseases of relatives. Have any transfusions of blood or blood substitutes been ever given, if yes – has the patient showed  any reactions on them? Genetic anamnesis: Can the patient remind any genetic diseases in his family? What is  the state of health or cause of death of close relatives (if somebody of relatives had died  – indicate in which age it took place). Has (had) somebody of relatives diabetes mellitus, bronchial asthma or another chronic hereditary-predisposed  diseases? Special attention should be paid for diseases with clinical manifestation similiar to these in the patient.

 

 

Diseases of the urinary system

 

 

Diseases of the urinary system come among the first in the list of diseases the most frequently occurring. In some cases the kidneys may be the locus of primary pathology. These are comparatively rare congenital abnormalities and genetic nephropathies. Inflammatory affections of the renal parenchyma, such as diffuse glomerulonephritis of infectious allergic nature, pyelonephritis arising in inflammatory processes of the urinary tract (cystitis, pyelitis) due to extension of inflammation onto the renal parenchyma, and focal nephritis in sepsis occur more commonly. The group of metabolic-dystrophic diseases of the kidneys includes their acute affections in various poisonings with nephrotoxic substances, in shock, and also chronic diseases such as amyloidosis and, to a certain extent, nephrolithiasis. The kidneys are often the site of tumours (especially frequently hypernephroid cancer or hypernephroma). Affections of the renal vessels are not infrequent. Traumatic affections of the kidneys often occur in surgery and treatment of urinary diseases.

The other group includes affections of the kidneys that are secondary to diseases of the other organs and systems: essential hypertension, atherosclerosis, diabetes mellitus, gout, collagenosis, general infections, etc.

In many untreated or improperly treated cases, primary or secondary affections of the kidneys cause dystrophic changes iephrons, development of connective tissue with its subsequent cicatrization and cirrhosis of the kidneys (nephrosclerosis) which is manifested clinically by signs of progressive renal failure.

 

 

 

Diffuse Glomerulonephritis

 Video: palpation of kidneys.mpg

Diffuse glomerulonephritis is the general infectious allergic disease with predominant affection of the glomerular vessels. Acute and chronic glomerulonephritis are distinguished.

Aetiology. Acute diffuse glomerulonephritis usually develop after acute infectious diseases, such as tonsillitis, scarlet fever, acute respiratory diseases, pneumonia, and otitis. Especially important are disease caused by group A haemolytic streptococcus, most frequently of type XII. But nephritis can arise also after infectious diseases caused by other bacteria e.g. pneumococci or staphylococci. Acute nephritis sometimes develops following overcooling, especially in damp weather. Cases were reported acute nephritis developing after vaccination.

Pathogenesis. Acute nephritis typically arises not during an infectious disease but only following a period of time, usually 2-3 weeks later. Attempts to isolate the streptococcus from the kidney tissue end in failure. Thus, the onset of acute nephritis usually coincides with the period antibodies to streptococcus are produced. This indicates that acute nephritis is not simply an infectious disease but an infectious al disease.

It is suggested that bacterial antigens, that get into the blood during infection, injure the kidney tissue, whose affected proteins art as an antigen to stimulate the production of the corresponding antibodies in the reticuloendothelial system. The antigen-antibody complexes are fixed in the endothelial and epithelial cells of the renal glomeruli and also in the  basal membrane of the glomerular capillaries to cause their injury. Both kidneys are always involved in acute diffuse glomerulonephritis and all glomeruli are equally affected. This distinguishes the affection from focal nephritis and confirms its allergic nature.

It is necessary to note that both the glomerular capillaries and vessels of the other organs and tissues are affected in acute glomerulonephritis. Nephritis is thus the general vascular disease. Cases have been described when in the presence of a marked clinical picture of the disease (oedema, hypertension), the urinary symptoms were insignificant or absent. But as a rule the glomerular apparatus of the kidneys is affected in acute nephritis which is explained by the specific character of their function as the excretory organ.

Clinical picture. The clinical picture of acute glomerulonephritis is quite specific and is determined by the main three syndromes: oedema, arterial hypertension, and changes in the urine (haematuria and proteinuria). The patients would usually complain of oedema, which arise first on the face, under the eyes, and then extend onto the entire body and the extremities. Development of oedema is explained by disordered capillary permeability and aldosterone hypersecretion by the adrenal cortex. Headache and heaviness in the head are frequent symptoms. They are explained by increased arterial pressure and, in some cases, intracranial pressure. Vision can be deranged due to spasm of the retinal vessels and haemorrhages into the retina. Many patients complain of general fatigue and reduced work capacity.

In the presence of a pronounced oedema and massive pleural effusion, and when the heart muscle is overloaded due to markedly increased arterial pressure, patients with acute nephritis suffer from severe dyspnoea, sometimes with attacks of asphyxia (like in cardiac asthma).

Edema

 

The patient with acute nephritis would often complain of dull lumbar pain. The gravity of the disease depends on the degree of oliguria. The diuresis decreases while the patient may have frequent tenesmus. Complete anuria occurs in some cases. If haematuria is marked, the urine looks like meat wastes.

Inspection of the patient reveals his specific appearance: pallid skin, edematous face, swollen eyelids, and oedema of the trunk. Some patients assume the forced semireclining or sitting position because of pronounced dyspnoea. Renal eclampsia occurs in grave cases. The onset of an eclampsia attack is heralded by increasing arterial pressure and a severe headache. The extent and the character of oedema can be established by palpation. The pulse of the patient should also be felt. Acute nephritis is characterized by a tense pulse which is sometimes slow. The apex beat is somewhat shifted to the left and increased due to myocardial hypertrophy which soon develops in the presence of arterial hypertension.

Percussion of the chest in the presence of generalized oedema reveals free fluid in the pleural cavity (transudate) and congestion in the lung root region (dulled tympany). The left border of the heart extends beyond the corresponding midclavicular line.

Normal or harsh respiration is heard by auscultation. In the presence of pronounced congestion, dry and moist congestive rales are heard.

Auscultation of the heart reveals bradycardia (due to the reflex transmitted in increased  pressure from the aorta onto the vagus nerve through n. depressor).

The first sound is sometimes decreased at the apex. If the heart muske is much overloaded, the gallop rhythm is heard. The second sound isd usually accentuated over the aorta due to increased arterial pressure.

Viseo: Pasternatsky’s symptom.mpg

 

X-ray studies of the chest confirm the presence of pleural effusion and congestion in the lung roots. Dilatation and hypertrophy of the left ventricle are clearly determined (the heart apex is rounded). Sphygmomanometry is of great help in establishing a diagnosis. It reveals one of the main symptoms of acute nephritis, i.e. arterial hypertension. Systolic pressure increases to 200—220 mm Hg, but in some cases it is not so high. Diastolic pressure increases to 100-160 mm Hg almost in all cases.

Electrocardiography reveals signs of hypertrophy and overload of the left-ventricular myocardium. The amplitude of ECG waves decreases in pronounced oedema of the trunk.

Kidney at ultrasound examination

 

Changes in the urine are characteristic of acute nephritis. During development of oedema, diuresis usually decreases to oliguria. The urine of patients with acute nephritis usually contains much protein and erythrocytes due to the increased permeability of the renal capillaries. If haematuria is pronounced, urine can be reddish-brown (the colour of meat wastes). Microscopy of the urinary sediment usually reveals the presence of casts (mainly hyaline casts) and cells of renal epithelium. The nitrogen excretory function of the kidneys is usually not affected in acute nephritis. Nitrogenous slags can only accumulate in the blood in serious cases attended by anuria. The clearance tests reveal more or less considerable reduction of glomerular filtration.

 

The infectious allergic character of acute glomerulonephritis is confirmed by immunological shifts: the content of a₂– and b-globulins in the blood increases during the acute period.

Active leucocytes in urine

 

Acute glomerulonephritis often proceeds without pronounced symptoms which make it difficult to identify it and hence to prescribe the appropriate treatment. But mild and indistinct forms of glomerulonephritis, like acute forms of this disease with classical clinical symptoms, give rise to chronic glomerulonephritis, unless the appropriate therapy is given.

 

Renal scanogram in a healthy individual (1) and pyelonephritis (2)

 

Contrast X-ray examination of kidneys

Plaine X-ray, contrast excretory urogram, radionucleic examination of kidneys

 

Renal eclampsia. The gravest and even dramatic complication of acute glomerulonephritis is renal eclampsia which occurs in 4-10 per cent of patients (mostly in children and women). During a convulsive attack, the patient may be heavily contused or his ribs may be fractured. Cases reported where patients died from cerebral circulatory disorders or oedema; true, such cases are rare. Attacks of eclampsia usually leave no consequence. It is interesting to note that eclampsia sometimes serves, .is a stimulus to a rapid regress of the disease and patient’s recovery.

 

Degree of nephroptosis (I, II, III)

 

 

Selective transfemoralnal angiogram. The right renal artery shows nephroptosis

 

Course. Acute glomerulonephritis usually lasts only a few weeks or months. The first sign of beginning recovery is resolution of oedema and further decrease in arterial pressure. Small haematuria and proteinuria can persist for months following disappearance of the main symptoms. Some patients do not recover completely and the disease becomes chronic.

Treatment. Patients with acute nephritis should be taken to hospital. It is important that the air in the ward should be warm and dry; drafts should be absent. Sodium chloride intake should be restricted to 0.5-1.5 g a day, which promotes resolution of oedema and normalization of arterial pressure. Protein intake should also be slightly decreased (at the expense of meat protein).

Prednisolone and other corticosteroid hormones having anti-allergic and anti-inflammatory properties are efficacious means of pathogenetic therapy of acute nephritis. Hypotensive preparations are given to control hypertension; furocemid and other diuretics should be given to remove oedema.

Prophylaxis. Hardening of the body and also thorough sanation of the infection foci (carious teeth, chronic tonsillitis, sinusitis, and the like) are required.

CHRONIC GLOMERULONEPHRITIS

Aetiology and pathogenesis. Chronic diffuse glomerulonephritis is a relatively common disease. It is often secondary to the acute form of this disease if the patient is not timely and properly treated. In other patients, chronic glomerulonephritis occurs suddenly, without acute nephritis in their anamnesis, but it can be suspected that the chronic disease was preceded by acute nephritis which however was latent, without manifest symptoms, and therefore not identified in proper time.

Chronic diffuse glomerulonephritis can sometimes be secondary to nephropathy of pregnancy which was not treated properly.

Great importance is now attached to the auto-immune mechanism in the pathogenesis of chronic glomerulonephritis. Antibodies to altered proteins of the renal tissue are probably formed in patients with the disease, in addition to formation of antibodies to streptococcus. This maintains the inflammatory process in the kidneys and is the cause of chronic progressive course of the disease.

Pathological anatomy. The kidneys are not enlarged, or enlarged only slightly during the first period of the disease, which lasts several years. In the final stage of the disease, the kidneys are markedly diminished in size, their surface is granular, the renal tissue is firm (arteriosclerotic kidney). Microscopy in chronic nephritis reveals mostly intracapillary inflammation in the glomeruli with gradual obliteration of the capillary loops and the capsule cavity and conversion of the glomerulus into a scar or hyaline node. Dystrophic changes occur in the epithelium of the renal tubules.

Clinical picture. Two periods can be easily distinguished in the of the disease: the first period, when the nitrogen secretory function of the kidneys is impaired only insignificantly (the stage of renal compensation), and the second period, during which this function is affected substantially (the stage of renal decompensation).

The symptoms of the first period are the same as in acute nephritis. The patient may complain of weakness, more or less persistent headache, dizziness, and oedema. But the gravity of these symptoms is usually less significant than in acute nephritis. The disease is often asymptomatic and is only revealed accidentally, during out-patient examination. Objective studies help to establish increased arterial pressure and hypertrophy of the left ventricle. Urinalysis reveals proteinuria and cylindruria. The presence of waxy casts is especially important diagnostically. The urinary sediment usually contains a small quantity (less frequently, considerable quantity) of leached erythrocytes. The blood serum cholesterol content is increased. More or less significant  hypoproteinaemia is observed due to permanent teinuria.

Symptoms of the second, or final, period of the disease gradually due to the progressive nephrosclerosis. Low indices of clearance tests indicate decreased quantity of functioning kidney tissue. The filtration capacity of the kidneys remains unchanged for a long time and only decreases during exacerbation of the process. The concentration capacity of the kidneys gradually decreases along with the decrease in the specific gravity of the urine. Removal oitrogenous slags from the body is maintained during this period by polyuria (evacuation of much liquid from the body). Nocturnal diuresis increases by the compensatory mechanism as well: it is two thirds-one half of the daily diuresis (nycturia). As the concentration capacity of the kidneys is affected to a greater extent, the specific gravity of the urine becomes low and its variations between 1.009 and 1.011 during the course of the day (and under the effect of dry food) are insignificant (isohyposthenuria). The content of nitrogenous slags in the blood of patients (urea, creatinine, indican) increases during this period.

Symptoms of uraemia develop: weakness becomes more considerable, the patient complains of lassitude, headache, nausea, skin itching, unpleasant ammonium breath, and impaired vision. Not long before death, the patients develop uraemic coma.

Facies nephritica

 

Course. Chronic nephritis usually lasts from 2-3 to 10-15 years. The first period of the disease (renal compensation) is long; the second period (decompensation) is shorter. During the course of the disease, there occur more or less prolonged periods of exacerbation, which are usually provoked by cooling or infections; exacerbations are followed by remissions.

Several clinical forms of chronic glomerulonephritis are differentiated by the character of its course and prevailing symptoms. The nephrotic form is characterized by oedema, the urinary syndrome, and a comparatively rapid course. The hypertensive form is comparatively benign and is characterized by the hypertensive syndrome and insignificant changes in the urine. The mixed form is characterized by oedema, changes in the urine, and arterial hypertension. This form of glomerulonephritis is the gravest and comparatively rapid: a pronounced renal failure develops in 2-3 years. Finally, there is the latent form of the disease, which is not manifested by oedema or pronounced hypertension; the changes in the urine are only insignificant; renal failure develops at late terms, often only in 10- 15 years. As a rule, the patient dies of renal failure.

Treatment. Patients with exacerbations are prescribed bed-rest, a dairy and vegetable diet with restricted sodium chloride (to 1.5-2.5 g/day) and containing at least 1 g/kg protein. The daily protein intake in the nephrotic form and hypoproteinaemia should be slightly increased. Foci of chronic infection (carious teeth, tonsillitis, etc.) should be treated. Infectious foci are treated with antibiotics. Good effect in the treatment of exacerbated nephritis (nephritic form of diffuse glomerulonephritis) is attained with prolonged use of chloroquine diphosphate (in the absence of marked hypertension or azotaemia). The course of treatment continues for several months. Stable clinical remission and even recovery of patients can sometimes be obtained with this therapy.

Symptomatic therapy in hypertensive and oedematous forms of chronic nephritis includes hypotonics and diuretics (hypothiazide, furocemid). Sanatorium therapy is often very helpful to patients with hypertensive and nephrotic forms of glomerulonephritis with compensated renal function.

Control of azotaemia is important in the treatment of uraemia. The intake of animal protein (meat) should be limited to 18-30 g/day. Broad spectrum antibiotics and also sour milk products (yoghourt, soar milk) are given to inhibit the putrefactive process in the intestine. In the absence of tendency to oedema, ample liquid is indicated. Group B vitamins, ascorbic acid, glucose, repeated blood transfusions, gastric lavage with sodium hydrocarbonate, sodium hydrocarbonate enema are used to control toxicosis. Peritoneal dialysis and haemodialysis (artificial kidney) are more effective means to control uraemic toxicosis. These means do not remove the cause^,of uraemia but only prolong the patient’s life. More prospective treatment of severe forms of chronic nephritis is transplantation of the kidneys.

Hemodialisis

 

Prophylaxis. Prophylaxis consists in timely treatment of acute and chronic focal infections (tonsillitis, sinusitis, carious teeth, paradontosis, etc.). Patients with chronic glomerulonephritis should he regularly inspected.

 

Pyelonephritis

Pyelonephritis is a serious bacterial infection of the kidney that can be acute or chronic.

Description of Pyelonephritis

One of the most common renal diseases, acute pyelonephritis is a sudden inflammation caused by bacteria. It primarily affects the interstitial area and the renal pelvis or, less often, the renal tubules.

 

Chronic pyelonephritis is persistent kidney inflammation that can scar the kidneys and may lead to chronic renal failure. This disease is most common in patients who are predisposed to recurrent acute pyelonephritis, such as those with urinary obstructions or vesicoureteral reflux.

Causes and Risk Factors of Pyelonephritis

Doctors believe that the bacterial infection causing pyelonephritis may sometimes develop elsewhere in the body and travel through the bloodstream to the kidney. Far more commonly, however, the infection is the result of bacteria from outside the body traveling back up the urinary stream through the urethra to the bladder and eventually to the kidneys, in which case it is known as an ascending infection. This may explain why women, whose urethras are short and in close proximity to the anus, a potential source of bacteria, have four times as many cases of pyelonephritis as men.

The flow of urine backward is known as reflux and may be caused by an anatomical defect or by an obstruction. In the former case, instead of a tight valve between the bladder and the ureter, there is a wide opening. When the bladder contracts during urination, the urine goes both ways, out through the urethra and back up through the ureters. The defect is not easy to correct and those who have it are subject to repeat infections.

Obstructions that cause reflux in women are commonly in the form of a stricture, or scar tissue, itself formed from infection or inflammation in the urethra. In young men, such strictures form less often and usually are a consequence of a sexually transmitted infection. In older men, the prostate is commonly responsible for obstruction to the flow of urine.

Reflux can also be caused by the insertion of catheters or instruments such as cystoscopes for diagnosis or treatment. The introduction of any foreign body into an area of obstruction is fraught with danger of infection which can be more difficult to treat.

Symptoms of Pyelonephritis

No matter what the underlying cause, the symptoms of acute bacterial pyelonephritis are often the same. The first indications are usually shaking chills, accompanied by a high fever and pain in the joints and muscles including flank pain. Attention may not be drawn to the kidneys at all.

The situation may be especially confusing in children, when high temperature may suddenly bring on a seizure or a change in mental state, or in the aged, where fever may bring confusion, or the infection may be masked by generalized aches and pains.

There may be irritative voiding symptoms (burning when urinating, a sense of urgency, or increased frequency of urination).

In acute infections, the symptoms develop rapidly, the fever noted first, followed by possible changes in the color of the urine, and then tenderness in the flank. As the kidney becomes more inflamed, pain, loss of appetite, headache, and all the general effects of infection develop. This type of kidney pain differs from renal colic pain of kidney stones in that it is continuous and does not come in waves, stays in one spot, and may be worse by moving around.

While patients with chronic pyelonephritis may have acute infections, sometimes there are no symptoms, or the symptoms may be so mild that they go unnoticed. This carries the risk that the infectious inflammatory disease may progress slowly undetected over many years until there is enough deterioration to produce kidney failure. Thus, hypertension (high blood pressure) or anemia or symptoms related to renal insufficiency may be the first indication of trouble. Unfortunately, irreversible damage may have already taken place.

Diagnosis of Pyelonephritis

Your physician will take a medical history, perform a physical exam, and recommend tests including blood tests and blood cultures, urinalysis and urine culture, and possibly an ultrasound study of the kidneys.

Treatment of Pyelonephritis

Treatment centers on antibiotic therapy appropriate to the specific infecting organism, after identification by urine culture. When the infecting organism cannot be identified, therapy usually consists of a broad-spectrum antibiotic. Symptoms may disappear after several days of antibiotic therapy. Although urine usually becomes sterile within 48 to 72 hours, the course of such therapy is 21 days. Patients with severe infections or complicating factors require hospitalization at least initially. In some patients, surgery may be necessary to relieve obstruction or correct an anatomical anomaly. Follow-up treatment includes reculturing the urine several weeks after drug therapy stops in order to rule-out reinfection.Patients at high risk of recurring urinary tract and kidney infections – such as those with prolonged use of an indwelling (Foley) catheter- require long-term follow-up.Diseases of the urinary system come among the first in the list of diseases the most frequently occurring. In some cases the kidneys may be the locus of primary pathology. These are comparatively rare congenital abnormalities and genetic nephropathies. Inflammatory affections of the renal parenchyma, such as diffuse glomerulonephritis of infectious allergic nature, pyelonephritis arising in inflammatory processes of the urinary tract (cystitis, pyelitis) due to extension of inflammation onto the renal parenchyma, and focal nephritis in sepsis occur more commonly. The group of metabolic-dystrophic diseases of the kidneys includes their acute affections in various poisonings with nephrotoxic substances, in shock, and also chronic diseases such as amyloidosis and, to a certain extent, nephrolithiasis. The kidneys are often the site of tumours (especially frequently hypernephroid cancer or hypernephroma). Affections of the renal vessels are not infrequent. Traumatic affections of the kidneys often occur in surgery and treatment of urinary diseases.

The other group includes affections of the kidneys that are secondary to diseases of the other organs and systems: essential hypertension, atherosclerosis, diabetes mellitus, gout, collagenosis, general infections, etc.

In many untreated or improperly treated cases, primary or secondary affections of the kidneys cause dystrophic changes iephrons, develop­ment of connective tissue with its subsequent cicatrization and cirrhosis of the kidneys (nephrosclerosis) which is manifested clinically by signs of progressive renal failure .

ACUTE GLOMERULONEPHRITIS

Aetiology. Acute diffuse glomerulonephritis usualy develops acute infectious diseases, such as tonsillitis, scarlet fever, acute respii diseases, pneumonia, and otitis.’Especially imp7)TtanTare diseases c by group A haemolytic streptococcus, most frequently of type XI nephritis can arise also after infectious diseases caused by other bat e.g. pneumococci or staphylococci. Acute nephritis sometimes de¹ following overcooling, especially in damp weather. Cases were repor acute nephritis developing after vaccination.

Pathogenesis. Acute nephritis typically arises not during an infe disease but only following a period of time, usually 2-3 weeks late jtempts to isolate the streptococcus from the kidney tissue end in fi Thus, the onset of acute nephritis usually coincides with the period antibodies to streptococcus are produced. This indicates that nephritis is not simply an infectious disease but an infectious a disease.

It is suggested that bacterial antigens, that get into the blood dur fection, injure the kidney tissue, whose affected proteins act as an a  to stimulate the production  of the corresponding  antibodies  I reticuloendothelial system. The antigen-antibody complexes are fi  the endothelial and epithelial cells of the renal glomeruli and also ‘   basal membrane of the glomerular capillaries to cause their injury kidneys are always involved in acute diffuse glomerulonephritis a glomeruli are equally affected. This distinguishes the affection fron nephritis and confirms its allergic nature.

It is necessary to note that both the glomerular capillaries and ves / the other organs and tissues are affected in acute glomerulonep Nephritis is thus the general vascular disease. Cases have been des when in the presence of a marked clinical picture of the disease (oe hypertension), the urinary symptoms were insignificant or absent. B rule, the glomerular apparatus of the kidneys is affected in acute ne which is explained by the specific character of their function as t cretory organ.

Pathological anatomy. The kidneys of those who died from acute nephritis are of size or slightly enlarged; their colour is brown or greyish-brown. Malpighi corpuscle form of small tubercles, can be seen on section. Microscopy of the renal tissue in th stage of the disease reveals enlarged and hyperaemic glomeruli; during further progrei disease, microscopy reveals ischaemia of the glomeruli due to spasm of the capillar fibrinoid swelling of the capillary walls, proliferation of their endothelium, accumul coagulated proteinous exudate in the space between the capillary loops and the glo capsule, blood stasis, thrombosis of the capillary loops, and haemorrhages. Path changes occur in both kidneys in all cases. Epithelium of the renal tubules is affe   larkedly. Intra- and extracapillary glomerulonephritis is mostly differentiated; depending on le character of the inflammation, glomerulonephritis may be exudative (serous, fibrinous, nd haemorrhagic) and productive.

At later stages of the disease, inflammatory phenomena subside in renal tissue, prolifera-lon of endothelium in glomerular loops decreases, and patency of the capillaries is restored.

Clinical picture. The clinical picture of acute glomerulonephritis is mite specific and is determined by the main three syndromes: oedema, irterial hypertension, and changes in the urine (haematuria and pro­linuria). The patients would usually complain of oedema, which arise first an the face, under the eyes, and then extend onto the entire body and the extremities. Development of oedema is explained by disordered capillary permeability and aldosterone hypersecretion by the adrenal cortex, Headache and heaviness in the head are frequent symptoms. They are ex­plained by increased arterial pressure and, in some cases, intracranial pressure. Vision can be deranged due to spasm of the retinal vessels and  haemorrhages into the retina. Many patients complain of general fatigue and reduced work capacity.

In the presence of a pronounced oedema and massive pleural effusion, and when the heart muscle is overloaded due to markedly increased arterial pressure, patients with acute nephritis suffer from severe dyspnoea,sometimes with attacks of asphyxia (like in cardiac asthma).

The patient with acute nephritis would often complain of dull lumbar pain. The gravity of the disease depends on the degree of oliguria. The  diuresis decreases while the patient may have frequent tenesmus. Complete anuria occurs in some cases. If haematuria is marked, the urine looks like meat wastes.

Inspection of the patient reveals his specific appearance: pallid skin, oedematous face, swollen eyelids, and oedema of the trunk. Some patients assume the forced semireclining or sitting position because of pronounced dyspnoea. Renal eclampsia occurs in grave cases. The onset of an^;eclarrtp-sia attack is heralded by increasing arterial pressure and a severe headache. The extent and the character of oedema can be established by palpation. The pulse of the patient should also be felt. Acute nephritis is characterized by a tense pulse which is sometimes slow. The apex beat is somewhat shifted to the left and increased due to myocardial hypertrophy which soon develops in the presence of arterial hypertension.

Percussion of the chest in the presence of generalized oedema reveals free fluid in the pleural cavity (transudate) and congestion in the lung root region (dulled tympany). The left border of the heart extends beyond the corresponding midclavicular line.

Normal or harsh respiration is heard by auscultation. In the presence of pronounced  congestion,   dry   and  moist  congestive  rales  are heard.

Auscultation of the heart reveals bradycardia (due to the reflex transmitted in increased pressure from the aorta onto the vagus nerve through n. depressor).

The first sound is sometimes decreased at the heart apex. If the heart muscle is much overloaded, the gallop rhythm is heard. The second sound is usually accentuated over the aorta due to increased arterial pressure.

X-ray studies of the chest confirm the presence of pleural effusion and congestion in the lung roots. Dilatation and hypertrophy of the left ventricle are clearly determined (the heart apex is rounded). Sphygmomanome-try is of great help in establishing a diagnosis. It reveals one of the main symptoms of acute nephritis, i.e. arterial hypertension. Systoiic pressure increases to 200—220 mm Hg, but in some cases it is not so high. Diastolic pressure increases to 100-160 mm Hg almost in all cases.

Electrocardiography reveals signs of hypertrophy and overload of the left-ventricular myocardium. The amplitude of ECG waves decreases in pronounced oedema of the trunk.

Changes in the urine are characteristic of acute nephritis. During development of oedema, diuresis usually decreases to oliguria. The urine of patients with acute nephritis usually contains much protein and erythrocytes due to the increased permeability of the renal capillaries. If haematuria is pronounced, urine can be reddish-brown (the colour of meat wastes). Microscopy of the urinary sediment usually reveals the presence of casts (mainly hyaline casts) and cells of renal epithelium. The nitrogen ex­cretory function of the kidneys is usually not affected in acute nephritis. Nitrogenous slags can only accumulate in the blood in serious cases attended by anuria. The clearance tests reveal more or less considerable reduction of glomerular filtration.

The infectious allergic character of acute glomerulonephritis is con­firmed by immunological shifts: the content of a₂– and 7-globulins in the blood increases during the acute period.

Acute glomerulonephritis often proceeds without pronounced symptoms which make it difficult to identify it and hence to prescribe the appropriate treatment. But mild and indistinct forms of glomerulonephritis, like acute forms of this disease with classical clinical symptoms, give rise to chronic glomerulonephritis, unless the appropriate therapy is given.

The gravest  and  even  dramatic  (Tareev)  complication  of acute

         glomerulonephritis is renal eclampsia which occurs in 4—10 per cent of patients (mostly in children and women). During a convulsive attack, the patient may be heavily contused or his ribs may be fractured. Cases were reported where patients died from cerebral circulatory disorders or lung oedema; true, such cases are rare. Attacks of eclampsia usually leave no consequence. It is interesting to note that eclampsia sometimes serves as a stimulus to a rapid regress of the disease and patient’s recovery.

Course. Acute glomerulonephritis usually lasts only a few weeks or months. The first sign of beginning recovery is resolution of oedema and  : further decrease in arterial pressure. Small haematuria and proteinuria can persist for months following disappearance of the main symptoms. Some patients do not recover completely and the disease becomes chronic.

Treatment. Patients with acute nephritis should be taken to hospital. It is important that the air in the ward should be warm and dry; drafts should be absent. Sodium chloride intake should be restricted to 0.5-1,5 g a day, which promotes resolution of oedema and normalization of arterial pressure. Protein intake should also be slightly decreased (at the expense of meat protein).

Prednisolone and other corticosteroid hormones having anti-allergic and anti-inflammatory properties are efficacious means of pathogenetic therapy of acute nephritis. Rauvolfia is given to control hypertension; furocemid and other diuretics should be given to remove oedema.

Prophylaxis. Hardening of the body and also thorough sanation of the infection foci (carious teeth, chronic tonsillitis, sinusitis, and the like) are required.

CHRONIC GLOMERULONEPHRITIS

Aetiology and pathogenesis. Chronic diffuse glomerulonephritis is a relatively common disease. It is often secondary to the acute form of this disease if the patient is not timely and properly treated. In other patients, chronic glomerulonephritis occurs suddenly, without acute nephritis in their anamnesis, but it can be suspected that the chronic disease was preceded by acute nephritis which however was latent, without manifest symptoms, and therefore not identified in proper time.

Chronic diffuse glomerulonephritis can sometimes be secondary to nephropathy of pregnancy which was not treated properly. Chronic nephritis is one of the three classical forms of Bright’s disease.

Great importance is now attached to the auto-immune mechanism in the pathogenesis of chronic glomerulonephritis. Antibodies to altered pro­teins of the renal tissue are probably formed in patients with the disease, in addition to formation of antibodies to streptococcus. This maintains the inflammatory process in the kidneys and is the cause of chronic progressive course of the disease.

Pathological anatomy. The kidneys are not enlarged, or enlarged only slightly during the first period of the disease, which lasts several years. In the final stage of the disease, the kidneys are markedly diminished in size, their surface is granular, the renal tissue firm (arteriosclerotic kidney). Microscopy in chronic nephritis reveals mostly intracapiilary inflam­mation in the glomeruli with gradual obliteration of the capillary loops and the capsule cavity and conversion of the glomerulus into a scar or a hyaline node. Dystrophic changes occur in the epithelium of the renal tubules.

Clinical picture. Two periods can be easily distinguished in the coi of the disease: the first period, when the nitrogen secretory function of kidneys is impaired only insignificantly (the stage of renal compensate and the second period, during which this function is affected substant (the stage of renal decompensation).

The symptoms of the first period are the same as in acute nephritis. patient may complain of weakness, more or less persistent headache, tigo, and oedema. But the gravity of these symptoms is usually less sig cant than in acute nephritis. The disease is often asymptomatic and is revealed accidentally, during out-patient examination. Objective st\ help establish increased arterial pressure and hypertrophy of the left ve cle. Urinalysis reveals proteinuria and cylindruria. The presence of i «asts^is especially important diagnostically. The urinary sediment us contains a small-quantity (less frequently, considerable quantity) of le ed erythrocytes. The blood serum cholesterol content is increased. Mo less significant hypoproteinaemia is observed due to permanent teinuria.

Symptoms of the second, or final, period of the disease de\ gradually due to the progressive nephrosclerosis. Low indices of clear tests (especially insulin and PAH clearance tests) indicate decreased qu -ty of functioning kidney tissue. The filtration capacity of the kidney /mains unchanged for a long time and only decreases during exacerbatic the process. The concentration capacity of the kidneys gradually decn along with the decrease in the specific gravity of the urine. Remov; nitrogenous slags from the body is maintained during this perioi polyuria (evacuation of much liquid from the body). Nocturnal diures creases by the compensatory mechanism as well: it is two thirds^jone ha the daily diuresis (nycturia). As the concentration capacity of the kidne affected to a greater extent, the specific gravity of the urine becomes and its variations between 1.009 and 1.011 during the course of the (and under the effect of dry food) are insignificant (isohyposthenuria). content of nitrogenous slags in the blood of patients (urea, creatinine dican) increases during this period.

Symptoms of uraemia develop: weakness becomes more consider! the patient complains of lassitude, headache, nausea, skin itching, unj sant ammonium breath, and impaired vision. Not long before death patients develop uraemic coma.

Course. Chronic nephritis usually lasts from 2-3 to 10-15 years, first period of the disease (renal compensation) is long; the second pe (decompensation) is shorter. During the course of the disease, there o more or less prolonged periods of exacerbation, which are usually pro ed by cooling or infections; exacerbations are followed by remissions

Several clinical forms of chronic glomerulonephritis are differentite character of its course and prevailing symptoms. The nephrotic is characterized by oedema, the urinary syndrome, and a corn-lively rapid course. The hypertensive form is comparatively benign is characterized by the hypertensive syndrome and insignificant ges in the urine. The mixed form is characterized by oedema, changes e urine, and arterial hypertension. This form of glomerulonephritis is gravest and comparatively rapid: a pronounced renal failure develops -3 years. Finally, there is the latent form of the disease, which is not ifested by oedema or pronounced hypertension; the changes in the e are only insignificant; renal failure develops at late terms, often only 0-15 years. As a rule, the patient dies of renal failure, treatment. Patients with exacerbations are prescribed bed-rest, a dairy vegetable diet with restricted sodium chloride (to 1.5-2.5 g/day) and taining at least 1 g/kg protein. The daily protein intake in the nephrotic it and hypoproteinaemia should be slightly increased. Foci of chronic :ction (carious teeth, tonsillitis, etc.) should be treated. Infectious foci treated with antibiotics. Good effect in the treatment of exacerbated ihritis (nephritic form of diffuse glomerulonephritis) is attained with ilonged use of chloroquine diphosphate (in the absence of marked >ertension or azotaemia). The course of treatment continues for several j tnths. Stable clinical remission and even recovery of patients cari netimes be obtained with this therapy.

Symptomatic therapy in hypertensive and oedematous forms of chronic-phritis  includes hypotonics  (reserpin)  and  diuretics  (hypothiazide, rocemid). Sanatorium therapy is often very helpful to patients with pertensive and nephrotic forms of glomerulonephritis with compensated nal function.

Control of azotaemia is important in the treatment of uraemia. The hi­ke of animal protein (meat) should be limited to 18—30 g/day. Broad lectrum antibiotics and also sour milk products (yoghourt, sour milk) are ven to inhibit the putrefactive process in the intestine. In the absence of ndency to oedema, ample liquid is indicated. Group B vitamins, ascorbic :id, glucose, repeated blood transfusions, gastric lavage with sodium ydrocarbonate, sodium hydrocarbonate enema are used to control tox-;osis. Peritoneal dialysis and haemodialysis (artificial kidney) are more ef-ective means to control uraemic toxicosis. These means do not remove the ause of uraemia but only prolong the patient’s life. More prospective reatment of severe forms of chronic nephritis is transplantation of the adneys.

Prophylaxis. Prophylaxis consists in timely treatment of acute and chronic focal infections (tonsillitis, sinusitis, carious teeth, paradontosis, stc). Patients with chronic glomerulonephritis should be regularly inspected.

ACUTE PYELONEPHRITIS

Aetiology and pathogenesis. Acute pyelonephritis arises as a result of infection spreading from the renal pelvis onto the kidney tissue in acute pyelitis, or as a result of infection of the kidney or its pelvis via haematogenic route in the presence of infectious foci in the patient’s body (chronic tonsillitis, osteomyelitis). It may also develop during acute infec­tious diseases (acute tonsillitis, sepsis, typhoid fever, etc.). Penetration of the bacteria into the kidney and the pelvis does not always provoke acute pyelonephritis or focal nephritis: bacteriuria without symptoms of involve­ment of the renal tissue is often observed. Difficult urine outflow from the kidney (stone in the ureter, twisting of the ureter) stimulates development of pyelonephritis.

Pathological anatomy. The kidneys are slightly enlarged, the mucosa of the renal pelvis is inflamed and oedematous, ulcerjatior+ls-possible. If urine outflow is obstructed, the pelvis containxpus. Inflammatory infiltration of the renal tissue develops and purulent foci can be found in some parts of the kidney.

Clinical picture. The patient’s condition is grave: high irregular fever, chills, dull lumbar pain. If inflammation spreads over onto the urinary bladder and the urethra, the patient feels tenesmus and sharp pain during urination.

Study of the urine reveals pyuria and bacteriurin. In complete obstruc­tion of the ureter and unilateral affection there may be no changes in the urine. Obliterated forms of acute pyelonephritis may also be observed (usually in the presence of grave general diseases). In such cases the kidney affection can only be suspected from the urinalysis.

Treatment. Antibiotics, sulpha and nitrofuran drugs (furadonin) are recommended.

CHRONIC PYELONEPHRITIS

Aetiology and pathogenesis. Pyelonephritis often arises in patients with chronic pyelitis due to transition of the inflammatory process from the renal pelvis onto the renal tissue. Nephrolithiasis facilitates fixation of the infection in the pelves and its spreading onto the renal tissue. Chronic pyelonephritis is usually caused by conventionally pathogenic flora, in­testinal escherichia; less frequently the disease is provoked by enterococ-cus, Proteus, or other infection. As infection spreads from the renal pelvis onto the renal parenchyma, the papillae are first affected, and then the medullar and cortical layers of the kidney. The kidney contracts as a The process is often unilateral. If both kidneys are involved, the e> affection may differ.

Clinical picture. Involvement of the renal tissue in the process al clinical picture of pyelitis to make it similar to that of < glomerulonephritis: hypertension develops, the concentrating andexcreting functions of the kidneys are gradually deranged, and u develops. But as distinct from chronic glomerulonephritis, pyelon< is characterized by involvement of only one kidney or asymmetrica tion of the kidneys. This can be revealed by intravenous or retr pyelography, separate study of the urine from the right and left kidn tained by catheterization of the ureters, and also by separate stu sorae substances excreted by the kidneys. Clearance tests are useful they can reveal early signs of involvement of the distal tubules delayed excretion of phenol red and decreased excretion coefl Radiographic methods, such as renography and scanning, are also u; the purpose.

Pyelonephritis is characterized by the signs of infectious inflamr of the renal pelves, i.e. by the presence of bacteriuria, leucot (especially the presence of active leucocytes known as Sternheimer-f cells in the urinary sediment), and also deformation of the renal pe revealed by pyelography. Bacteriological study of the urine is o! significance: (cultivation of the urine on a nutrient media, and dete tion of bacterial sensitivity to antibiotics). It should be rememben urine specimens from women should only be taken by catheterizal the bladder. Differential diagnosis is facilitated by puncture biopsy kidneys.

At the terminal stage, due to involvement of both kidneys and dc ment of nephrosclerosis, all functional tests for kidneys are not mative. Death of patients is in most cases caused by uraemia.

Treatment. Infection is treated by antibiotics, sulpha drug: nitrofuran derivatives. Symptomatic therapy is given to control  azotaemia (at the terminal stage).

 

Main Clinical Syndromes

Renal Oedema

Oedema of renal aetiology is quite specific in most cases and can easily be differentiated from oedema of other origin, e.g. cardiac oedema, by the affection of loose connective tissue (the eyelids, the face) rather than of the lower extremities. Renal oedema can develop and resolve quickly. In pro­nounced cases, oedema is usually uniform over the entire trunk and the ex­tremities (anasarca). Not only the skin but also subcutaneous fat and the internal organs become oedematous. The liver usually becomes oedematous and enlarged, but in renal diseases the enlargement of the liver is usually proportional to enlargement of the other ograns, and is never so pronounced as in cardiac oedema. Greater or lesser amount of fluid is ac­cumulated in the serous cavities, e.g. in the pleural, abdominal, and pericardial cavities. Oedema can be revealed by palpation. It can also be confirmed by the McClure-Aldrich test: 0.2 ml of isotonic sodium chloride solution is injected into the skin on the median surface of a forearm and the time of disappearance of the resulting weal is noted. In a healthy sub­ject, the weal is resolved within one hour. In the presence of a marked oedematous syndrome, the dynamics of oedema during treatment can be better assessed by repeating the test in several days with measurement of girths of the extremities and the abdomen at the same level, by determining the fluid level in the pleural and abdominal cavities, by weighing the patient, and also by determining daily diuresis and water balance of the body (the ratio of the taken and eliminated liquid during 24-hour period).

 

Nephrotic Syndrome

The nephrotic syndrome (symptom complex) is characterized by pTo-lunced proteinuria, hypoproteinaemia (mainly due to hypoalbumi-lemia), hyperlipidaemia (hypercholesterolaemia), and oedema.

The nephrotic syndrome occurs in chronic glomerulonephritis, nyloidosis, malaria, sepsis, tuberculosis, collagenosis, diabetes mellitus, id certain other diseases. Less frequently the cause of the nephrotic syn-rome cannot be established immediately, but in most cases a detailed nalysis of anamnestic data and a thorough examination of the patient :veal chronic glomerulonephritis. These forms of the nephrotic syndrome ccur mostly in children. Cases where the cause of renal dystrophy is nclear are identified as lipid nephrosis.

It is believed that the nephrotic syndrome is caused by metabolic lisorders, mostly upset fat and protein metabolism, with subsequent lerangement of trophies and capillary permeability in the glomeruli. Pro-ein and lipids contained in large quantity in primary urine of these patients nfiltrate the tubular wall to cause drastic dystrophy in the epithelial cells. rhe auto-immune mechanism is of great significance for the development of the chronic nephrotic syndrome. It has been proved by animal ex­periments: small doses of nephrotoxic serum provoke nephritis in rabbits; a picture characteristic of the nephrotic syndrome develops on administra­tion of large doses.

Pathological anatomy. The following morphological signs of the nephrotic syndrome develop, in addition to the changes characteristic for the main disease. The kidneys are enlarg­ed (“large white kidneys”) and their capsule is easily removed. Histological studies reveal dystrophic changes in the epithelium of the tubules, especially of the convoluted tubules. Lipid deposits can be found in the basal parts of the epithelial cells. The glomeruli are affected by dystrophy; especially specific are changes in podocytes and endothelial cells with which the disordered permeability of the glomerular membrane is associated.

Clinical picture. The main, and often the only complaint of patients is persistent oedema. It is especially pronounced on the face which becomes swollen and pallid, the eyelids are only a narrow slit, and the patient opens his eyes in the morning with difficulty. The legs, the loin, the skin of the abdomen and the hands are also affected by oedema. The oedema is mobile: when the skin is pressed by the finger, a depression remains in it which soon disappears. Fluid is accumulated also in the internal organs and the serous cavities. In typical cases the arterial pressure remains unchanged or even decreased.

As the oedema progresses, diuresis usually decreases and the patient often eliminates only 250-400 ml of urine a day. The specific gravity of the urine is high (1.030-1.040) and it contains much  protein, to 10-20 g/1 and more. Cases were reported where the urine contained 24 g/1 of protein. Fine dispersed molecules of albumins prevail among protein. It is believed that the increased filtration of the plasma protein through the glomerular capillary wall and also disordered reabsorption of protein molecules by the affected tubular epithelium are important in the aetiology of proteinuria in the nephrotic syndrome. Great quantity of hyaline, granular and\ waxy casts, and cells of renal epithelium are found in the urinary sediment. The presence of leucocytes and erythrocytes in the urinary sedimentyis not characteristic for the nephrotic syndrome. Doubly refracting cholesterol crystals are usually found, which are, as a rule, absent in renal diseases proceeding without the nephrotic syndrome.

A long-standing and persistent proteinuria causes protein depletion of the body and a stable reduction of its content in the blood plasma (1.5 and even 2 times). The albumins become especially deficient, and the albumin to globulin ratio, which is normally 1.2—2.0, decreases significantly. The content of a₂-globulins, and also 7-globulins, slightly increases. Pro­teinuria and hypoproteinaemia (especially hypoalbuminaemia) largely ac­count for oedema that develops in the nephrotic syndrome (see “Renal Oedema”). It has been established that the loss of protein in the urine is ag­gravated by the renal catabolism of plasma proteins (proteolysis of part of serum protein during its reabsorption in the tubules) and also, probably, by the increased protein loss through the alimentary tract.

Among the constant symptoms are pronounced hyperlipidaemia, increased blood serum concentration of cholesterol (to 13-15 mmol/1, i.e. 2 or 3 times as great), phospholipids, and neutral fat. These changes are probably secondary to upset protein metabolism and hypoproteinaemia. Laboratory studies reveal three characteristic signs of the nephrotic syn­drome: proteinuria, hypoproteinaemia, and upset lipid metabolism (hypercholesterolaemia).

The blood clearing function of the kidneys is not substantially affected in the nephrotic syndrome, and azotaemia does not develop for a long time. The main functional renal tests remaiormal for a long time, but the tubular secretion can decrease. Biopsy of the kidneys supplies valuable information concerning the nature of the nephrotic syndrome in chronic renal diseases.

Course. If the main disease does not progress, the nephrotic syndrome lasts foV years. Oedema and the urinary syndrome intensify at times usually when provoked by an attending infection. Patients with the nephrotic syn­drome are sensitive to coccal infection. They often develop recurrent pneumonia and erysipeloid inflammation of the skin. These patients usual­ly died before antibiotics were discovered. Vascular thrombosis is likely to occur in patients with the nephrotic syndrome. The prognosis depends mostly on the main disease and the attending infections.

Treatment. The main disease should be treated. In the presence of pro­ nounced hypoproteinaemia, the patient is prescribed a diet rich in proteins (2—2.5 g/kg body weight without reference to oedema) and poor in sodium chloride. Plasma or concentrated human albumin is given intravenously. Corticosteroids (prednisolone) and immunodepressants (imurane, etc.) are prescribed. If oedema is pronounced, the patient is given diuretics: furantril (furocemid), 0.04 g per os every other or third day, in combination with verosperon (0.075-0.15 g/day per os) to remove oedema. Sanatorium andhealth-resort therapy in dry climate (Central Asia) is recommended during relative remissions.

Renal Hypertension

Renal arterial hypertension is a symptojnatic hypertension caused by the affection of the kidneys or renal vessels and upset renal mechanism of arterial pressure regulation. Among all cases of arterial hypertension, renal hypertension makes about 10—15 per cent.

Many diseases of the kidneys, in the first instance acute and chronic glomerulonephritis, pyelonephritis, nephrosclerosis and various affections of the renal blood vessels are attended by elevated arterial pressure. This is underlain by the important role that the kidneys play in the regulation of arterial pressure. The juxtaglomerular apparatus of the kidneys, which is an accumulation of special cells at the vascular pole of the glomen the point where the artery nears the proximal end of the distal conv tubule, produces renin in the presence of ischaemia of the renal chyma. Renin acts on the liver-produced hypertensinogen, which is tion of a₂-globulin of plasma, to convert it into angiotensinogen. Th is converted enzymatically into angiotensin (hypertensin). Angi( stimulates hypersecretion of aldosterone, stenosis of arterioles, e creases arterial pressure. The current literature contains reports development of renal hypertension which is associated with hyposecretion of special hypotensive substances (e.g. prostaglandir It should be noted that due to diffuse spasm of arterioles, es hypertension also provides conditions  for atherosclerosis of the a disordered blood supply to various organs, the kidneys included, anc for the increased secretion of renin .

Headache is especially se /marked elevation of the arterial pressure. It is often attended by voi and paresthesia. As a rule, the work capacity is impaired ant deranged. The increased arterial pressure can be determined by feel pulse which appears to be tense. More accurately arterial pressure be measured instrumentally. Both systolic and diastolic pressure she measured; the latter pressure is sometimes very high. The second sc usually accentuated over the aorta.

High and persistent hypertension affects the heart. First, the ventricular muscle is hypertrophied due to constant overload. This determined by the increased apex beat, specific changes detecta X-rays (rounded heart apex) and electrocardiographically (deviation heart’s electrical axis to the left, a certain increase in the jR_t wave, an descent of the S-T_{ segment below the zero line, and the negative o phase r, ₂ wave).

At later stages, dystrophic changes occur in the myocardium beca vascularization lags behind the growth of the muscle weight to accoi the deficient blood supply; next, cardiosclerosis develops. At the time, atherosclerosis of the coronary vessels may develop due to upse metabolism, which is characteristic for arterial hypertension and other renal diseases attended by the nephrotic syndrome. Renal arterial hypertension involves specific changes in the fundus oculi I retinopathy). Anally, disorders in cerebral circulation with paralysis, deranged sen-sitivity, dysfunction of the pelvic organs, and also myocardial infarction can develop as a result of arterial hypertension and atherosclerosis.

It follows therefore that in certain kidney diseases, the renal hyperten­sion syndrome can be of primary significance in the clinical picture of the disease and can be decisive for its course and outcome.

Renal Eclampsia

Eclampsia (Gk ek, lampein to flash) usually develops in acute diffuse glomerulonephritis, but can also arise in aggravated chronic glomerulonephritis and nephropathy of pregnancy. The pathogenesis of eclampsia is largely underlain by increased intracranial pressure, Oedema of the cerebral tissue and cerebral angiospasm. Eclampsia in all these con­ ditions usually arises in pronounced oedema and increased arterial pressure. Attacks of the disease are provoked by salted food and excess liquid.

Renal Failure

Renal failure is toxicosis of the body caused by renal dysfunction (self-poisoning). yraemia_ is a severe form of renal failure. Renal failure and-uraemia occur in acute and chronic cases. Acute uraemia develops in poisoning with nephrotoxic substances (compounds of mercury and lead, carbon tetrachloride, barbiturates, etc.), in transfusion of incompatible blood, profuse haemolysis, and shock. Chronic uraemia develops in the final stage of many chronic renal diseases, such as chronic glomerulonephritis, pyelonephritis, amyloidosis, affections of the renal vessels, tumours of the kidneys, etc.

Pathogenesis. It consists in profound homeostatic disorders. It has been established that products of protein decomposition are accumulated in the blood of patients with uraemia. These are nitrogenous slags, such as urea, uric acid, creatinine, and other guanidiries. The content of indican, phenol and other aromatic substances that are formed in the intestine and pass into the blood through the intestinal wall (normally, these substances are eliminated from the blood by the kidneys) increases. Various compounds of sulphur, phosphorus, magnesium, and other substances are ac­cumulated; the ionic equilibrium is upset. Acidosis develops as a result of the accumulation of acid products and disordered production by the kidneys of ammonia that neutralizes the acids. Uraemia is attended by a grave affection of the liver and metabolic disorders.

Acute renal failure and acute uraemia develop due mainly to shock and the accompanying circulatory disorder (mostly in the kidneys). Anoxia develops to cause dystrophic changes in the renal glomeruli and tubules. In I other cases, when acute renal failure is due to poisoning or a grave in I tious disease, its pathogenesis is largely determined by the direct actioi I poisons and toxins on the renal parenchyma. In both cases glomer I filtration is deranged, diuresis decreases and oliguria develops; in se I cases anuria may occur. Salts of potassium, sodium, phosphorus, nit I     products and some other substances are retained in the body.

Acute renal failure rapidly develops and the patient’s cond I becomes grave: vomiting, mental confusion, deranged respiration upset heart activity are observed. The glomeruli are affected by ischa to raise the arterial pressure; oedema develops in anuria. The patient die unless anuria and azotaemia are removed during the first few da; the course of the disease is benign, diuresis increases but the concentr ^capacity of the kidneys remains impaired for some time; the renal fun gradually normalizes and the patient recovers.

Clinical picture. Acute renal failure varies slightly, depending o  character of the main disease. In many cases it proceeds with some ge symptoms which make a syndrome. Four stages of acute renal failui distinguished: (1) initial stage lasting from several hours to 6-7 da] clinical picture is characterized by the main symptoms of the di (traumatic or transfusion shock, severe infectious disease, poisoning, _ (2) oligoanuric stage characterized by changes in diuresis (to con / anuria), uraemic toxicosis, and water-electrolyte disorders. Proteh cylindruria, and erythrocyturia are revealed on examination, oligoanuric stage can end with death of the patient or his recovery. 1 latter case, diuresis suddenly or gradually increases (the third or poi stage). The specific gravity of the urine is low, the concentrate residual products of protein metabolism in the blood decreases, \ electrolyte balance is restored and the pathological changes in the disappear. The fourth stage, recovery, begins with normalizatic diuresis; it lasts from 3 to 12 months.

Development of chronic renal failure is determined by the progr affection of the kidney parenchyma. The latent period of chronic failure, when renal dysfunction has no clinical symptoms and can oi revealed by special laboratory methods, and the manifested pi characterized by the marked clinical picture of uraemia, are distirgui The latent period can only be revealed by special tests carried oi concentrating capacity of the kidneys and cold food and by the Zimi test. The patient’s urine is usually of low specific gravity (below 1 Variations in specific gravity are only insignificant (isohyposthenuria^ clearance tests reveal disordered reabsorption in the renal tubules a glomerular filtration. Mild renal dysfunction can be reveale radioisotope nephrography. It is believed that the first signs of renal f ents with chronic renal diseases only appear when the functioning :hyma diminishes to at least one fourth of its normal size. jgressive renal failure is attended by changes in the circadian varia-n urination: isuria or nycturia are observed. The concentration and >n tests reveal significant disorders in the concentrating capacity of Ineys, pronounced isohyposthenuria (the specific gravity of all urine lens varies from 1.009 to 1.011, i.e approaches the specific gravity of a ultrafiltrate, the “primary” urine). More pronounced disorders in jrption and glomerular filtration are determined by the clearance ind nephrography. Concentration of nitrogenous substances in the gradually increases. Residual nitrogen increases several times (its al content is 14.2-28.5 mmol/1 or 20-40 mg/100 ml). Laboratory :s reveal increased concentration in the blood of various products of in decomposition: urea (3.23—6.46 mmol/1 iorm and 10-15 and times higher in renal failure), creatinine (0.088-0.176 mmol/1 in and 1-1.3 mmol/1 in renal failure), indican (0.68-5.44/xmol/1 in i). It should be noted that the increased blood indican content is often irst and the most reliable sign of chronic renal failure, because its i content does not depend on the protein concentration of food and use it is not accumulated in tissues.

loderately increased concentration of products of nitrogenous decom-/ ion in the blood (azotaemia) may have no effect on the subjective-dtion of the patient for a certain period of time. But later some exter-;hanges become manifest and they can be used for the diagnosis of mia. Certain symptoms of uraemia depend on partial compensation of 1 failure by a more active involvement of the skin, mucosa, and the stive glands in the excretory processes. Decomposition of the urea (ex-:d by the mucosa of the air ways and the mouth) to ammonia by the eria accounts for the specific uraemic breath. In serious cases, the :mic breath can be felt by the physician as he approaches the patient’s . It is believed that the uraemic breath can be felt when the concentra-i  of residual  nitrogen  in the  blood  exceeds  70 mmol/1  (about mg/100 ml).

The nitrogenous substances, and in the first instance urea, are liberated :he gastric mucosa and decomposed to form ammonia salts. These salts tate the mucosa of the stomach and the intestine to stimulate nausea, niting (uraemic gastritis), and diarrhoea (uraemic colitis). Irritation of respiratory mucosa causes laryngitis, tracheitis, and bronchitis. Severe matogingivitis develops. The mucosa becomes affected by ulcers and :rosis. Urea crystals (as a white powder) can sometimes be seen on the ient’s skin. This is especially noticeable at the orifices of the sweat nds (at the base of hairs). Strong itching develops and the patient scratches his skin. Poisons accumulated in the blood are also liberated by the serous membranes. Uraemic pericarditis is especially characteristic. It can be revealed by auscultating the heart using a stethoscope: the specific coarse pericardial friction can be heard. This friction appears in the terminal period and is a sign of  approaching death.

Memory and sleep become deranged due to general poisoning; weakness, dull headache, somnolence, apathy and deranged vision are characteristic. Examination of the fundus oculi reveals narrowed arteries and dilated veins, oedema of the papilla of the optic nerve, and whitish local foci (retinopathy). Development of retinopathy is explained by trophic disturbances due toThe vascular spasm of the fundus oculi vessels and uraemic toxicosis which intensifies these changes. The pupils are usually narrowed.

Metabolic disorders are pronounced: the patient develops cachexia; the liver and bone marrow functions are affected by dystrophy; toxic uraemic anaemia develops which is usually attended by leucocytosis and throm­bocytopenia. The tendency to haemorrhages develops due to a decreased blood platelet count, disorders in the blood coagulating system and in­creased capillary permeability (as a result of toxicosis). Haemorrhages of the gastro-intestinal tract, urinary tract, uterus, and the nose may develop. Skin haemorrhages also occur. The body temperature slightly decreases.

Later, toxicosis increases, the patient’s consciousness becomes dimm­ed, and uraemic coma develops. Periods of stupor alternate with periods of excitation, hallucinations, and noisy slow breathing with very deep inspira- ₍ tions (Kussmaul’s breathing); respiration with alternating periods of hyperpnoea and apnoea (Cheyne-Stokes respiration) occurs less frequently. At the terminal stage the patient is in a deep coma; muscular twitchings occur at times and the patient dies.

There is no universally accepted classification of chronic renal failure at the present time. Three stages are usually differentiated: (1) the initial stage with insignificantly increased residual nitrogen and creatinine and moderately decreased glomerular filtration; (2) pronounced stages (IIA and IIB) with marked azotaemia and electrolyte disorders and (3) terminal stage with a pronounced clinical picture of uraemia.

Main principles of treatment. Patients with acute renal failure should be immediately taken to hospital. Treatment should be begun as early as possible and aimed at eliminating the main aetiological factors (removal of nephrotoxic substances or their detoxication, giving large doses of plasma or blood substitutes for hypovolaemic shock). The electrolyte equilibrium should be corrected simultaneously. Mannitol or furocemid should be given intravenously in the initial functional stage of acute renal failure to restore diuresis. Haemodialysis (artificial kidney) or peritoneal dialysis are necessary in grave cases.

The protein content of the diet is controlled in patients with chronic renal failure. Therapeutic action on the aetiological factor and pathogenic mechanisms should be attempted (antibacterial therapy in pyelonephritis, immunodepressants in chronic glomerulonephritis, etc.). The water-electrolyte equilibrium and acid-base balance are corrected simultaneously. The necessary symptomatic therapy with hypotensive, cardiovascular and other preparations should be carried out. In severe cases, permanent chronic haemodialysis is carried out or the kidneys are transplanted to prolong the patient’s life.