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
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 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
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  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.
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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.
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 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 .

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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.

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  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

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  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.

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 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
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  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,

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 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
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 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

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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.

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 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

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 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;

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 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.

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