Presentation 4

Diseases of hematopoietic system Anemia  Reduction in hb concentration accompanied by reduction in red cell mass  Develops w/n rate of RBC production fails to keep pace with that of RBC destruction or loss  Based on underlying mechanism anemia divided in to two  Anemia of blood loss or RBC destruction( hemorrhage, hemolytic anemia )  Anemia of impaired RBC production Hemolytic anemia  Characterized by the ff features  Shortening of the normal RBC life span & premature destruction  Accumulation of products hb catabolism in the body  Marked increase in erythropoiesis within the bone marrow  Classified in to

1

 ↑Hereditary & acquired  Extravascular hemolysis  Occurs within the mononuclear phagocyte system(spleen, liver, bone marrow)  Account majority of hemolytic anemia  Cause anemia, jaundice, heposplenomegally  Intravascular hemolysis  Occures within the vascular system  Cased by mechanical injury, autoimmunity, exogenous factors  Causes hemoglobinemia, hemoglobinuria. jaundice  In all types of hemolytic anemia the marrow become hyperplastic  Megaloblastic anemia  Impaired DNA synthesis with megaloblastic change  Caused by deficiency of vit B12 or follic acid  RBC shows an ↑ in size 2

 Iron deficiency anemia  Most common medical disorder  Causes include  Inadequate dietary source  Impaired intestinal absorption of fe  Loss of Fe dueto hemorrhage or intravascular hemolysis  RBCes appear small (microcytic) and appear much pailure ( hypochromic )  Aplastic anemia  is a disorder characterized by  the suppression of multipotent myeloid stem cells  with resultant anemia, thrombocytopenia, and neutropenia (pancytopenia)  In more than half of cases, aplastic anemia is idiopathic.  In other cases, exposure to a known myelotoxic agent can be identified, such as  whole-body irradiation (as may occur in nuclear plant accidents) or  use of myelotoxic drugs.  Drugs and chemicals are the most common causes of secondary aplastic 3

 Morphology  The bone marrow typically is markedly hypocellular, with greater than 90% of the intertrabecular space being occupied by fat.  A number of secondary changes may accompany marrow failure.  Hepatic fatty change may result from anemia, and  thrombocytopenia and granulocytopenia may give rise to hemorrhages and bacterial infections, respectively.  POLYCYTHEMIA  denotes an increased concentration of RBCs, usually with a corresponding increase in Hb level.  Such an increase may be  relative, when there is hemoconcentration caused by decreased plasma volume, or  absolute, when there is an increase in total RBC mass.  Relative polycythemia results from any cause of dehydration, such as deprivation of water, prolonged vomiting, diarrhea, or excessive use of diuretics. 4

Bleeding Disorders  are characterized clinically by abnormal bleeding  may either be spontaneous or become evident after some inciting event (e.g., trauma or surgery).  Abnormal bleeding may have as its cause  (1) a defect in the vessel wall,  (2) platelet deficiency or dysfunction, or  (3) a derangement of coagulation factors.  Abnormalities of vessels can contribute to bleeding in several ways.  Increased fragility of the vessels is associated with  severe vitamin C deficiency (scurvy)  systemic amyloidosis  chronic glucocorticoid use,  rare inherited conditions affecting the connective tissues, and  a large number of infectious and hypersensitivity vasculitides. include meningococcemia, infective endocarditis, the rickettsial diseases,

5

 A hemorrhagic diathesis that is purely the result of vascular fragility is characterized by  (1) the apparently spontaneous appearance of petechiae and ecchymoses in the skin and mucous membranes (probably from minor trauma),  (2) a normal platelet count and tests of coagulation (PT, PTT), and  (3) a bleeding time that is usually normal.  Deficiencies of platelets (thrombocytopenia)  characterized by  spontaneous bleeding,  a prolonged bleeding time, and  normal PT and PTT.  A platelet count of 100,000/μL or less is generally considered to constitute thrombocytopenia  spontaneous bleeding does not become evident until the count falls below 20,000/μL. 6

 causes  A decrease in the production with marrow failure or injury;  idiopathic aplastic anemias,  drug-induced marrow failure, and  marrow infiltration by tumors.  Accelerated destruction of platelets  is often immunologically mediated,  resulting from formation of antiplatelet antibodies or adsorption by platelets of immune complexes formed in the circulation.  may be associated with well-known autoimmune diseases such as SLE, or  it may appear as an apparently isolated derangement (idiopathic thrombocytopenic purpura .

7

Coagulation disorder  result from either congenital or acquired deficiencies of clotting factors.

 Acquired coagulation disorders are usually associated with deficiencies of multiple clotting factors.  vitamin K deficiency may be associated with a severe coagulation defect, because this nutrient is essential for the synthesis of prothrombin and clotting factors VII, IX, and X.  The liver is the site of synthesis of several coagulation factors  parenchymal diseases of the liver are common causes of hemorrhagic diatheses.  Hereditary deficiencies have been identified for each of the coagulation factors.  These deficiencies characteristically occur singly.  Hemophilia A, resulting from deficiency of factor VIII, and  hemophilia B (Christmas disease), resulting from deficiency of factor IX,  Both are transmitted as X-linked recessive disorders  most others are autosomal disorders .

8

White Cell Disorders Disorders of white cells may be associated with  a deficiency of leukocytes (leukopenias) or  proliferations that may be reactive or neoplastic. Leukemias Malignant neoplasms of WBC and their precursors There is reversal the usual ratio of red to white blood cells (↑ wbc ) They are characterized by  Diffuse replacement of bone marrow by leukemic cells  Appearance of abnormal immature wbces in the peripheral circulation  Wide spread infiltration of the liver, spleen, LN, 7 other tissues throughout the body Classification  Lymphocytic leukemia involve lymphocytes & may be acute or chronic  Myelocytic involve the bonemarroow & interfer with maturation of all blood cells except lymphocytes

9

 ALL most frequent leukemia in childhood ( peak b/n 2 to 4 year )  AML seen mostly b/n 13 to 39 years and CML b/n ages 30 & 50 years  CLL is disorder of older persons  Cause  the cause of acute leukemia remains unknown in the majority of patients  several risk factors related to an increased incidence have been identified.  radiation exposure  Benzene exposure  Exposure to phenylbutazone, arsenic, and chloramphenicol  Cytotoxic therapy  RNA viruses  Clinical manifestation  Leukemic cells are immature & mobile  They are capable of ↑ rate of proliferation & prolonged life span  They are unable to perform the functions of leukocytes ( ineffective in phagocytosis & immune function )

10

 They tend to interfere with maturation of the normal bm cells ( RBC, platelets )  They are able to travel throughout the circulatory system, cross the blood brain barrier , infiltrate many body organs  Lyphomas  are two types  Hodgkin’s disease  Malignant neoplasm of the lyphatic structure  Charactrized by painless & progressive enlargement of lyphoid tissue  Usually a single or groups of nodes involved  It has a characteristic neoplastic cell, the Reed-Sternberg cell  an excellent response to treatment, with the large majority of patients being cured.  The cause of Hodgkin's lymphoma remains unclear but suspected is EBV  Clinical Manifestations  usually manifested as lymphadenopathy  typically in the cervical, axillary, or mediastinal areas,

11

Diseases of the gastrointestinal system SALIVARY GLAND DISEASES Sialadenitis  Inflammation of the major salivary glands  may be of viral, bacterial, or autoimmune origin.  Dominant among these causations is the infectious viral disease mumps,  produce enlargement of all the major salivary glands  predominantly the parotids.  the dominant cause is a paramyxovirus, an RNA virus related to the influenza and parainfluenza viruses.  It usually produces a diffuse, interstitial inflammation marked by edema and a mononuclear cell infiltration and, sometimes, by focal necrosis.  Bacterial sialadenitis  most often occurs secondary to ductal obstruction resulting from stone formation (sialolithiasis)  The sialadenitis may be largely interstitial or cause focal areas of

12

Salivary gland tumors  About 80% of tumors occur within the parotid glands  most of the others in the submandibular glands.  Males and females are affected about equally, usually in the sixth or seventh decade of life.  In the parotids 70% to 80% of these tumors are benign,  whereas in the submaxillary glands only half are benign.  The dominant tumor arising in the parotids is the benign pleomorphic adenoma, which is sometimes called a mixed tumor of salivary gland origin.  Much less frequent is the papillary cystadenoma lymphomatosum (Warthin tumor).  Collectively, these two types account for three fourths of parotid tumors.  Whatever the type, they present clinically as a mass causing a swelling at the angle of the jaw.

13

 Among the diverse cancers of parotid glands, the two dominant types are  (1) malignant mixed tumors arising either de novo or in preexisting, benign, pleomorphic adenomas and  (2) mucoepidermoid carcinoma (containing adenocarcinomatous and squamous cell carcinomatous features). Diseases of the esophagus  Achalasia  Incomplete relaxation of the lower esophageal sphincter in response to swallowing.  The three major abnormalities in achalasia are  (1) aperistalsis,  (2) partial or incomplete relaxation of the lower esophageal sphincter with swallowing, and  (3) increased resting tone of the lower esophageal sphincter

14

 in primary achalasia there is loss of intrinsic inhibitory innervation of the lower esophageal sphincter and smooth muscle segment of the esophageal body.  Secondary achalasia may arise from pathologic processes that impair esophageal function.  In most instances achalasia occurs as a primary disorder of uncertain etiology.  Achalasia is characterized clinically by  dysphagia and inability to completely convey food to the stomach.  Nocturnal regurgitation and aspiration of undigested food may occur.  ESOPHAGITIS  Injury to the esophageal mucosa with subsequent inflammation  The inflammation may have many origins:  prolonged gastric intubation,  uremia, ingestion of corrosive or irritant substances, and  radiation or chemotherapy, among others.

15

 presumed contributory factors are:  Decreased efficacy of esophageal antireflux mechanisms  Inadequate or slowed esophageal clearance of refluxed material  The presence of a sliding hiatal hernia  Increased gastric volume, contributing to the volume of refluxed material  MORPHOLOGY  Mild esophagitis  appear macroscopically as simple hyperemia  virtually no histologic abnormality.  severe esophagitis exhibits  confluent epithelial erosions or total ulceration into the submucosa.

16

 ESOPHAGEAL CARCINOMA  are two types:  squamous cell carcinomas and adenocarcinomas  risk factors for squamous cell carcinoma  Long-standing esophagitis  Achalasia  Alcohol consumption  Tobacco abuse  Deficiency of vitamins (A, C, riboflavin, thiamine, pyridoxine)  MORPHOLOGY  Squamous cell carcinomas  Early overt lesions appear as small, gray-white, plaquelike thickenings or elevations of the mucosa.  In months to years, these lesions become tumorous, taking one of three forms:  (1) polypoid exophytic masses that protrude into the lumen

17

 (2) necrotizing cancerous ulcerations that extend deeply and sometimes erode into the respiratory tree, aorta, or elsewhere and  (3) diffuse infiltrative neoplasms that impart thickening and rigidity to the wall and narrowing of the lumen.  Whichever the pattern, about  20% arise in the cervical and upper thoracic esophagus,  50% in the middle third, and  30% in the lower third.  Adenocarcinomas  appear to arise from dysplastic mucosa in the setting of Barrett esophagus.  they are usually in the distal one third of the esophagus and may invade the subjacent gastric cardia.  Initially appearing as flat or raised patches on an otherwise intact mucosa,  they may develop into large nodular masses or exhibit deeply ulcerative or diffusely infiltrative features 18

 Clinical Features.  Esophageal carcinoma is insidious in onset and  produces dysphagia and obstruction gradually and late.  Weight loss, anorexia, fatigue, and weakness appear, followed by pain, usually related to swallowing.  Diagnosis is usually made by imaging techniques and endoscopic biopsy Diseases of the stomach  GASTRITIS  inflammation of the gastric mucosa. 

majority of cases are chronic gastritis,

 occasionally, distinct forms of acute gastritis are encountered. 3. Chronic Gastritis  defined as the presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia  Causes are chronic infection by the bacillus Helicobacter pylori & autoimmune gastritis

 Morphology  the inflammatory changes consist of  a lymphocytic and plasma cell infiltrate in the lamina propria,  occasionally accompanied by neutrophilic inflammation of the neck region of the mucosal pits.  The inflammation may be accompanied by variable gland loss and mucosal atrophy  Read about acute gastritis  GASTRIC ULCERATION  Ulcers are defined as a breach in the mucosa of the alimentary tract that extends through the muscularis mucosae into the submucosa or deeper.  This is to be contrasted to erosions, in which there is a breach in the epithelium of the mucosa only.  Erosions may heal within days, whereas healing of ulcers takes much longer.  Although ulcers may occur anywhere in the alimentary tract, none are as prevalent as the peptic ulcers that occur in the duodenum and stomach.

20

Peptic Ulcers Peptic ulcers are chronic, most often solitary, lesions occur in any portion of the gastrointestinal tract exposed to the aggressive action of acid-peptic juices.  At least 98% of peptic ulcers are either in the first portion of the duodenum or in the stomach, in a ratio of about 4:1 Pathogenesis. There are two key facts.  First, the fundamental requisite for peptic ulceration is mucosal exposure to gastric acid and pepsin.  Second, there is a very strong causal association with H. pylori infection.  induced by an imbalance between the gastroduodenal mucosal defenses and the countervailing aggressive forces that overcome such defenses,

21

 host mechanisms that prevent the gastric mucosa from being digested  Secretion of mucus  Secretion of bicarbonate  Rapid gastric epithelial regeneration  Robust mucosal blood flow  Mucosal elaboration of prostaglandins  Among the "aggressive forces,"  H. pylori  NSAIDs  Cigarette smoking  Alcohol  Morphology  they are defects in the mucosa that penetrate at least into the submucosa, and often into the muscularis propria or deeper.  Most are round, sharply punched-out craters 2 to 4 cm in diameter 22

 Clinical Features.  epigastric gnawing, burning, or boring pain  a significant minority first come to light with complications such as hemorrhage or perforation.  The pain tends to be worse at night and occurs usually 1 to 3 hours after meals during the day.  Classically, the pain is relieved by alkalis or food, but there are many exceptions.  Nausea, vomiting, bloating, belching, and significant weight loss (raising the specter of some hidden malignancy) are additional manifestations  Read about Gastric Carcinoma

23

Disease of intestine INFLAMMATORY BOWEL DISEASE

 including ulcerative colitis and Crohn's disease,  are chronic inflammatory diseases of the gastrointestinal tract.  ulcerative colitis  The inflammatory response is largely confined to the mucosa and submucosa,  is confined to the colon, and colectomy is a curative procedure.  Crohn's disease  the inflammation extends through the intestinal wall from mucosa to serosa.  can involve any part of the gastrointestinal tract,  the distal end of the small bowel and the colon are most commonly involved.  Resection of the inflamed segment is not curative of Crohn's disease, and inflammation is likely to recur. 24

 Pathology  In ulcerative colitis,  inflammation begins in the rectum,  extends proximally a certain distance,  and then abruptly stops, with a clear demarcation between involved and uninvolved mucosa.  In mild disease, there are superficial erosions, whereas in more severe disease, ulcers may be large but superficial and penetrate the muscularis mucosa only in very severe disease.  Inflammatory polyps or pseudopolyps may be present.  In Crohn's disease,  the bowel wall is thickened and stiff.  The mesentery, which is thickened, edematous, and contracted, fixes the intestine in one position.  Transmural inflammation may cause loops of intestine to be matted together..

25

 All layers of the intestine are thickened, and the lumen is narrowed.  “Skip lesions” with two involved areas separated by a length of normal intestine suggest Crohn's disease.  Colonic inflammation with rectal sparing is more consistent with Crohn's disease than with ulcerative colitis

26

 Colorectal Carcinoma  A great majority (98%) of all cancers in the large intestine are adenocarcinomas.  almost always arise in adenomatous polyps that are generally curable by resection.  About 25% of colorectal carcinomas are in the cecum or ascending colon, with a similar proportion in the rectum and distal sigmoid  Tumors in the proximal colon tend to grow as polypoid, exophytic masses that extend along one wall of the capacious cecum and ascending colon  carcinomas in the distal colon are tend to be annular, encircling lesions that produce so-called napkin-ring constrictions of the bowel and narrowing of the lumen  Clinical Features.  Colorectal cancers remain asymptomatic for years;

27

 In Cecal and right colonic cancers  fatigue,  weakness, and  iron deficiency anemia.  In Left-sided lesions  occult bleeding,  changes in bowel habit, or  crampy left lower quadrant discomfort.

28