Dysphagia Definition A difficulty with any of the stages of swallowing; difficulty in passing food and/or liquid from the mouth to the
stomach. Causes Oropharyngeal Esophageal
Mechanical Functional 1. Oral cavity: inflammations,
dental problems, xerostomia 2. Pharynx: pharyngitis, tumors 3. Neurological disorders:
stroke, Parkinson, myasthenia gravis.
4. Radiotherapy to the area of head and neck cause extensive fibrosis.
5. Medications e.g. sedatives, hypnotics and anticonvulsants
Intraluminal obstruction a. Foreign bodies b. Webs (in some cases of Plummer-‐Vinson syndrome) Intramural obstruction a. Strictures, following reflux esophagitis, peptic ulceration, or ingestion of corrosive alkali b. Neoplasms of the esophagus: Benign or Malignant Extrinsic compression a. Abnormal arteries: dysphagia lusoria b. Enlarged left atrium (mitral stenosis) and pericardial effusion c. Aortic aneurysms d. Hypertrophic vertebral osteophytes e. Mediastinal cysts and neoplasms. F. Esophageal diverticulae
1. Achalasia of the cardia 2. Muscular dystrophies and
polymyositis may affect the striated muscle of the upper esophagus
3. Myasthenia gravis 4. Plummer-‐Vinson syndrome 5. Progressive systemic sclerosis
(scleroderma) due to replacement of esophageal muscle by fibrosis, causing failure of peristalsis
6. Diffuse esophageal spasm 7. Aging: abnormalities of
peristalsis occur in the elderly
Pathology Refer next page
Clinical presentation
1. Drooling. 2. A feeling that food or liquid is sticking in the throat. 3. Discomfort in the throat or chest (gastro esophageal reflux). 4. A sensation of a foreign body or "lump" in the throat. 5. Weight loss and inadequate nutrition due to prolonged or more significant problems with swallowing 6. Coughing or choking caused by bits of food, liquid, or saliva not passing easily during swallowing, and being
sucked into the lungs.
Complication 1. Coughing and choking. 2. Respiratory problems. If food or liquid enters respiratory airway (aspiration); pneumonia, lung abscess or
upper respiratory infections can occur 3. Malnutrition and dehydration
Diagnosis 1. Examination of mouth and throat which may be aided by flexible laryngoscope which provides vision of the
back of the tongue, throat, and larynx. 2. Speech assessment 3. An exam by a neurologist may be necessary if the swallowing disorder stems from the nervous system,
perhaps due to stroke or other neurologic disorders.
Management 1. medication 2. swallowing and speech therapy 3. surgery if needed
Nb Odynophagia is used when there is pain during deglutition.
Explanation Dysphagia results from Plummer-‐Vinson
Syndrome It consists of severe iron deficiency anemia, koilonychia, atrophic glossitis, and dysphagia with female preponderance resulting from menstrual blood loss.
1-‐ Atrophy of the pharyngeal mucosa. 2-‐ web-‐like mucosal folds present in the upper esophagus.
Reflux esophagitis
Regurgitation of gastric acidic secretions to the lower esophagus leading to lower mucosal inflammation and mucosal abnormality
Sclerosis and stricture
Tumors of the esophagus
Benign tumors are less common than malignant tumors. The most common are leiomyomas. Malignant tumors may be a.Carcinoma: most common Sq.cc at upper 2/3 Adenocarcinoma at lower 1/3 b.Lymphoma & other sarcomas: rare
Esophageal obstruction.
Esophageal diverticulae
Traction or true diverticulae develop in the esophagus due to external forces pulling in the wall Pulsion or false diverticulae forcible distension from inside (Zenker’s divert.
Permanently distention with retained food
Achalasia Incomplete relaxation of lower sphincter during swallowing and this leads to functional obstruction Ganglion cells of the myenteric plexus are diminished or absent leading to Loss of inhibitory innervations to the sphincter and (Spasm) of the sphincter with dilatation of the upper segment (megaesophagus).
Causes : autoimmune, viral infections May occur secondary to Trypanosoma cruzi infection (Chagas disease). Clinical picture: dysphagia, regurgitation and aspiration. Histology: Inflammation in the area of M. plexus Complications: 5% develop squamous cell carcinoma, at younger age.
Progressive systemic sclerosis:-‐
(scleroderms)
There’s widespread fibrosis and degenerative changes that affect the skin, gastro-‐intestinal tract especially the esophagus, heart, muscles and other organs.
Fibrosis of the esophagus → Narrowing and loss of prestalsis
Acute peptic ulcer Definition Transient mucosal inflammatory process that may be asymptomatic
cause variable degrees of epigastric pain, nausea, and vomiting. In more severe cases there may be mucosal erosion, ulceration, hemorrhage, hematemesis, melena, or, rarely, massive blood loss.
Causes Heavy use of NSAIDs particularly aspirin Excessive Alcohol Heavy smoking ttt with Cancer chemotherapy Hypovolemia
Ischemia and Shock Severe Stress (burns, surgery, strokes, post infarction) Uremia Enterogastric reflux Corrosives (may cause perforation) Mechanical trauma
Chronic peptic ulcer Definition An increase in the number of lymphocytes and plasma cells in the gastric mucosa.
Stages Mildest degree of chronic gastritis is chronic
superficial gastritis, which involves the subepithelial region around the gastric pits.
Severe cases involve the glands in the deeper mucosa; this is commonly associated with gland atrophy (chronic atrophic gastritis) and intestinal metaplasia.
Causes ♣ Helicobacter pylori :Type B involves the antrum and is associated with Helicobacter pylori infection ♣ Autoimmune: Type A involves the body and is associated with pernicious anemia; ♣ Psychologic stress, caffeine, alcohol, and tobacco use were considered the primary causes of gastritis
Site ♣ First part of duodenum ♣ Stomach ♣ Lower esophagus
♣ Meckel's diverticulum ♣ Stomal (marginal) ulcer (gastro-‐jujenostomy)
Stomach protective mechanism
The anatomic integrity of the mucosa: The mucosal cells have a specialized apical surface membrane that resists the diffusion of acid into the cell. Gastric mucus: Mucin and HCO3 secreted by surface epithelial cells create a mucous layer that has a pH gradient which is very acid in the lumen to nearly neutral near the cell surface. Prostaglandins (E series), which are synthesized and secreted by gastric mucosal cells, have a cytoprotective effect on the gastroduodenal mucosa. They act to increase bicarbonate secretion, gastric mucus production, mucosal blood flow, and the rate of mucosal cell regeneration. Mucosal blood flow: Ischemia of the mucosa decreases mucosal resistance
Pathogenesis Imbalance between erosive effect ( H.Pylori, NSAIDs, smoking, etc ) and protective mechanism leads to ulcer formation Morphology Usually solitary, round-‐to-‐oval in shape
Often large (larger than 1 cm, rarely larger than 5 cm) and usually found on the lesser curvature or pyloric antrum Margins are either flush with the mucosal surface or slightly raised because of edema. The edge is punched out, the floor of the ulcer is smooth, and its base is thick and firm because of fibrosis. The mucosa around the ulcer is either normal or—in the stomach—shows changes of chronic gastritis. The mucosal folds around the ulcer appear to radiate outward from it, which is an effect of fibrous contraction of the base of the ulcer Microscopically, the base of a chronic peptic ulcer is composed of :-‐ 1-‐ A surface of necrotic layer 2-‐ Acutely inflamed layer 3-‐ A zone of granulation tissue. 4-‐ Extensive fibrosis of the base, with extension of fibrosis into the muscle wall. 5-‐ The epithelium at the edge of the ulcer shows regenerative hyperplasia, which frequently demonstrates marked cytologic atypia, mimicking neoplastic change
Clinical feature Epigastric pain (worse at night and relieved by food), bleeding (30%) Perforation (5%; accounts for 2/3 of deaths).
Complications Hemorrhage Perforation, penetration. Fibrosis…stenosis, hour-‐glass stomach Duodenal diverticulum Malignancy, rare, gastric not deudenal
Malabsorption syndrome Definition It is a state of abnormal intestinal absorption of nutrients resulting in malnutrition, weight loss and
osmotic diarrhea. Causes Luminal phase Cellular phase
Inadequate digestion ♣ Postgastrectomy ♣ Deficiency of pancreatic lipase
o Chronic pancreatitis o Cystic fibrosis o Pancreatic resection
♣ Zollinger-‐Ellison syndrome (high acid inhibits lipase)
Hypomotility states ♣ diabetes, scleroderma, visceral myopathy, amyloidosis
Deficient bile salt concentration ♣ Obstructive jaundice ♣ Bacterial overgrowth (leading to bile salt deconjugation)
o Stasis in blind loops, diverticula ♣ Interrupted enterohepatic circulation of bile salts
o Terminal ileal resection o Crohns' disease o Precipitation of bile salts (neomycin, cholestyramine)
Primary mucosal abnormalities ♣ Surgical resection ♣ Celiac disease ♣ Tropical sprue ♣ Whipple disease ♣ Radiation enteritis ♣ Amyloidosis ♣ Lymphatic obstruction
e.g. lymphoma
Pathology Explanation M/E or characteristics Celiac disease (Gluten-‐sensitive enteropathy)
-‐ 1:300 persons are affected, hypersensitivity to gliadin, a component of gluten (present in wheat flour) leading to blunted villi and increased intraepithelial lymphocytes. -‐ Changes disappear with gluten-‐free diet. -‐ Increased risk for lymphoma.
Flattening of the duodenal villi, they are almost absent. Flattening of the villi greatly decreases the surface area available for absorption. Numerous intraepithelial lymphocytes
Tropical sprue Malabsorption and diarrhea occurring in travelers and natives in certain tropical areas . -‐ Infectious etiology, responds to antibiotics. -‐ Histological changes resemble celiac disease
Whipple disease
A systemic disease that affects GIT, nervous system and joints. Caused by T. whippelii (gram-‐positive organism ) The causative organism can be demonstrated inside the macrophages.
Widening of the intestinal villi with numerous macrophages seen throughout the lamina propria with fat cysts.
Crohn’s disease A chronic inflammatory disorder that most affects any part of the GIT, commonly the ileum and colon. It is characterized by involvement of discontinuous segments of intestine (skip areas), non caseating epithelioid cell granulomas, and transmural (full-‐thickness) inflammation of the affected parts Site: terminal ileum and right colon (any part of the GIT).
Skip lesion : affected segments separated by healthy ones. Transmural affection: All layers up to the serosa with marked thickening of the wall. Deep fissure ulcers with mucosal edema giving the cobble-‐stone appearance.
Acute pancreatitis
Chronic pancreatitis Definition It is a chronic disease characterized by progressive destruction of the parenchyma with chronic
inflammation, fibrosis, stenosis and dilation of the duct system, and eventually impairment of pancreatic function.
Causes • Alcoholism and biliary calculi…..most important causes • Following acute episodes. • Cystic fibrosis • In 30-‐40% of cases no apparent cause can be identified.
Pathological changes
• Stenosis of the ducts • Calculi within duct system • Atrophy of acini • Chronic inflammation • Fibrosis
• The pancreas is shrunken and fibrotic, and the dilated duct contains numerous stones
• Atrophic lobules of acinar cells are surrounded by dense fibrous tissue infiltrated by lymphocytes.
• The pancreatic ducts are dilated and contain inspissated proteinaceous material.
Complications • Pleural effusion • Pancreatic pseudocyst • Diabetes • Pain from perineal fibrosis
• Pancreatic calcification • Stones in pancreatic duct • Ascites • Fat malabsorption • Obstructive jaundice
Diarrheal disorders Definition Diarrhea = Increased frequency or volume of stool (more than 250 gm/day). Types Explanation Causes
Secretory diarrhea
Intestinal cells secrete more water than they absorb
• cholera toxins • E.coli • entero-‐virus infection • preformed toxins of staphylococcal food
poisoning Osmotic diarrhea Due to the presence of non-‐absorbable
substances which increase the intra-‐luminal osmotic pressure leading to influx of water and electrolytes into the lumen.
• Patients with genetic lactase deficiency: diarrhea after milk ingestion due to lactose osmosis.
• Malabsorption syndrome . • Sorbitol or manitol
Exudative diarrhea
Purulent bloody stool (inflammation of the mucosa and/or hemorrhage)
• Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica
• Infections causing both tissue damage and toxins: Clostridium difficile
• Idiopathic inflammatory bowel disease
Mixed causes Reduced
absorption time
Alcohol induced disease Effects of chronic
alcoholism • Fatty liver, alcoholic hepatitis, and cirrhosis, which causes portal hypertension and increases the
risk of development of hepatocellular carcinoma. • Increases the risk for acute and chronic pancreatitis. • Gastritis and gastric ulcers. • Peripheral neuropathy associated with thiamine deficiency. • Cardiomyopathy . • Cancers of the oral cavity, pharynx, larynx, and esophagus. The risk is greatly increased by
concurrent smoking.
Neoplasia Definition Abnormal mass of tissue growth which exceeds and uncoordinated with normal tissue and that persists in the
same excessive manner after cessation of the stimuli which evoked the change =autonomous new growth
Structure Parenchyma Stroma Proliferating neoplastic cell
Made of transformed or neoplastic cell Determine the biological behavior of tumor Results from clonal proliferation of a single cell (monoclonal)
It is host derived, non – neoplastic component of tumor Made of CT and blood vessel of tumor Vascularity is related to tumor – angiogenesis factors (TAFs)
Classification According to biological behavior According to tissue of origin Benign
Malignant Locally malignant
Epithelial : adenoma, papilloma Mesenchymal: sarcoma Miscellaneous
Differences between benign and malignant Benign tumor Malignant tumor
Definition A single mass formed of mature tissue, slowly growing, remain localized
A mass formed of immature tissue grows rapidly and invades surrounding structures, lymphatic and blood vessel to form 2ry tumor
Origin Normal cell of parent tissue De novo or from a pre-‐existing premalignant lesion Rate of growth
Slow Rapid
Mode of growth
By expansion ; pushing the surrounding normal tissue without invasion
By expansion and infiltration ; destroy and invade surrounding normal tissue
Gross feature Single Number Begin single and metastasize Usually small Size Reach a large size within short time Capsulated Capsule Absent, non -‐ capsulated
Uniform, no hemorrhage or necrosis Small, well circumscribed, rounded or oval
Cut section
Usually shows hemorrhage and necrosis Fixed to the surrounding structures with irregular
outlines
Microscopic feature
No cellular atypia: tumor cell resemble parent tissue cell in both cytology and
histology
Cellular atypia
Cellular atypia is characteristic of cancer. Cell changes in both cytology and histology
Resemble the mother cell of origin With minimal mitosis
Cytology Pleomorphism Hyperchromatism
Increase nuclear/cytoplasmic ratio Increase mitotic fissure with abnormal form
Tumor giant cell Prominent nuclei
=anaplasia The pattern of arrangement same to the
origin tissue Histology The pattern of arrangement is variable and depends on
tumor grade Excess with few blood vessels 2ry changes less common
Stroma Poor with prominent vascularity 2ry changes are common
Behavior and prognosis
Don’t spread Don’t recur if well excised Don’t endanger patient life except in following conditions 1. Located in vital organ 2. Located in tubular organ 3. Produce hormones 4. Change into malignant
Spread Recur after excision Fatal due to
1. Local organ destruction due to direct spread 2. Destruction of distant organs by distant spread 3. Obstruction of hollow organs by distant spread 4. Anemia 5. Cachexia
Differentiation Well differentiated Well differentiated to undifferentiated
Tumor grade It is degree or resemblance of tumor cell to their mother cell origin both morphologically and functionally Based on microscopic features ( cytology and histology )
Functional differentiation
Better differentiated the cell, the more completely it retains the function of a normal cell
Spread of malignant tumors
Local Blood Lymphatic
Trancoelomic Natural passages Implantation
Methods of spreading
Local invasion Distant metastasis
It is the presence of tumor cells away from their site of origin without loss of continuity with the primary Tumor cells follows the way of the tumor to the surrounding This leads to adhesion of the tumor to the surrounding It can cause severe hemorrhage and obstruction of hollow organ
It is the presence of tumor cell away from the primary w/o continuity with it Metastases occurs through
1. Lymphatic 2. Blood vessel 3. Transcoelomic & seeding of body cavities 4. Natural passages 5. Implantation
Detachment of tumor cell from each other -‐ This occur due to loss of the intercellular glue
substance ( E adheren ) -‐ It results in loosening up of tumor cell Attachment of tumor cell of ECM This ECM includes -‐ Basement membrane w’ contains lamiin and
interstitial CT to adhere to the BM & interstitial CT
Degradation of the extracellular matrix -‐ Tumor cell then secrete proteases w’ cause
degradation of the ECM (eg type IV collagenase)
Migration of tumor cell This step occurs under the effect of certain chemotactic factors -‐ Tumor cell derived cytokines -‐ Cleavage products of matrix components -‐ Some growth factors
Lymphatic Typical of carcinoma -‐ Lymphatic emboli -‐ Lymphatic permeation Haemotogenous spread Typical of sarcoma Veins with thinner walls are more susceptible to penetrate Liver and lungs most frequent 2ry involved site Homing of tumor cell -‐ Lung -‐ Liver -‐ Bone marrow -‐ Brain -‐ Adrenal gland Seeding of body cavities Occurs whenever malignant neoplasm penetrate into an open field -‐ Peritoneal cavity -‐ Pleural cavity -‐ Pericardiac cavity -‐ Subarachnoid space Transcoelomic Common in carcinomas arising in the stomach or GIT giving metastatic deposits on the surface of ovary ( Krukenberg tumor )
Systemic effect of cancer in the host Neoplastic syndrome Most cancer symptoms are due to local effects of primary tumor or its metastasis
Paraneoplastic syndrome
Cancer produce remote effects not attributable to invasion of metastasis Eg: fever, nephrotic syndrome, neorologia, hypercalcemia, skin manifestation, etc
Cachexia Definition Characteristic wasting syndrome in cancer patients
Eg: anorexia, weight loss lethargy Causes Inadequate food intake
Impaired digestion, absorption Competition between host and tumor for nutrition Increased energy requirement of cancer patient (↑ 𝐵𝑀𝑅) TNF, other cytokines
Dysplasia Definition Abnormal growth
Colorectal adenocarcinoma Etiology Genetic influence
-‐ Pre existence ulcerative colitis / FAP coli syndrome -‐ Several mutations to different genes : APC, K-‐ras, P53 -‐ Hereditary non polyposis colorectal cancer syndrome ( Lynch syndrome ) Environmental influence -‐ Low content of unabsorbable vegetable fiber -‐ Corresponding high content of refined CHO -‐ High fat content -‐ Decrease intake of protective micronutrients ( Vit A,C,E)
FAP Autosomal dominant, Average onset is 25 years old Mostly colorectal , Minimum of 100 polyps are necessary for diagnosis Genetic defect on chromosome 5q21, APC tumor suppressor gene Precancerous: virtually 100% will develop cancer within 10=15 years
Carcinogenesis Chromosome instability pathway (adenoma carcinoma sequence) -‐ Genetic defect at 5q21, APC -‐ Germ – line or somatic mutations of cancer suppressor genes -‐ Methylation abnormalities (hypomethylation) which cause inactivation of normal alleles -‐ This leads to chromosome instability and protooncogene mutations and activation -‐ Homozygous loss of additional cancer suppressor genes and over expression of COX2 -‐ More additional mutations
Mismatch repair pathway ( microsatellite instability ) -‐ Germ – line somatic mutations of mismatch repair genes -‐ Alteration of second allele by LOH, mutation and promoter methylation -‐ Hypermethylation cause inactivation of tumor suppressor gene and inactivation of DNA
repair gene -‐ Lead to microsatellite instability or mutator phenotype ( increase mutation rate ) -‐ Accumulation mutations in genes that regulate growth, differentiation and or apoptosis
Symptoms Right colonic cancers -‐ Fatigue -‐ Weakness -‐ Anemia (IDA) -‐ Internal bleeding
Left colonic cancers -‐ Occult bleeding -‐ Bowel habit alteration (melena, diarrhea,
constipation) -‐ Left – lower quadrant cramps and
discomfort Sites 50% malignant ulcers in sigmoid colon and rectum
15% napkin ring lesion in descending colon and causing obstruction 10% mesenteric lymph nodes 15% polypoid lesion in ascending colon 10% in caecum
Spread Hematogenous, LN ,Retroperitoneum Shape Annular ,Ulcerating ,Polypoid M/E Neoplastic cell and stroma with variable glandular differentiation with loss polarity
-‐ Appear disorganized and adhere to each other Neoplastic cell shows all cellular criteria of malignancy -‐ Pleomorphism, hyperchromatism, increase N/C, prominent nuclei, increase mitotic figure Tumor invades deeply into colonic mucosa Tumor cells may continue to produce mucin
Diagnosis Imaging, endoscopy and biopsy, increased serum carcino-‐embryonic antigen
Staging ( Duke system ) Stage Invasion of colonic wall LN metastases Distant metastases 5 year survival rate A Mucosa and submucosa No No >90% B1 Muscle wall thickness No No 67% B2 Full thickness of muscle wall No No 55% C1 Partial muscle wall thickness Yes No 40% C2 Full thickness of muscle wall Yes No 20% D All Yes or no Yes 10% or <
TNM staging T= size or direct extent of the primary
tumor N= lymph node M=metastases
Tx: tumor cannot be ecaluated Tis: carcinoma in situ T1: submucosa T2: muscularis propria T3: subserosa T4: perforates the visceral peritoneum, directly invades organ
Nx: lymph node cannot be evaluated N0: tumor cell asent from regional LN N1: one to three pericolic LN (near spread) N2: four or more pericolic LN (distant spread) N3: tumor spread more distant and numerous
M0: no distant metastases M1: distat organs metastases
Diagnosis of tumor Clinical examination Radiological Laboratory ( tumor marker )
Laboratory diagnosis of cancer Specimen sample -‐ Excision of biopsy -‐ Incision biopsy -‐ Needle aspiration -‐ Cytologic smear
Immunohistochemistry -‐ Specific monoclonal antibodies help to
identify cell products or surface markers -‐ Determination of origin of cell population -‐ Detection of prognosis and therapeutic
markers Tumor marker
Alpha fetoprotein Hepatocellular carcinoma Germ cell tumours
Human chorionic gonadotropin (HCG) Trophoblastic tumors
Acid phosphatase Prostatic carcinoma
Carcinoembryonic antigen (CEA) Gastrointestinal tract neoplasia
Hormone products Endocrine tumors
Acute Viral Hepatitis Chronic Viral hepatitis Cirrhosis Def It is inflammatory process of the liver It is continuity of hepatitis can be
symptomatic or biochemical (elevated enzymes or presence of viral antigens) without steady improvement for more than 6 months
Chronic diffuse irreversible progressive liver disease characterized by -‐ Hepatocellular necrosis -‐ Hyperplasia of the surviving hepatocytes
forming regenerating, vascular derangement and diffuse fibrosis
Cause HAV, HBV, HCV, HDV, HEV Viral: HBV (+-‐ HDV) , HCV or mixed Autoimmune Drug induced : INH, methyl dopa Metabolic: congenital 𝛼1 anti trypsin deficiency Cryptogenic: idiopathic
Patho Liver cell injury is caused by: -‐ Direct cytopathic effect of the
virus -‐ Cell mediated immune response
(by cytotoxic T lymphocytes) Systemic manifestations are caused by -‐ Circulating immune complexes
May be an auto – immune mechanism
1. Fibrosis is the key feature 2. Type I and III collagens are deposited in
the lobule, creating delicate or broad septal tracts
3. Deposition of collagen in the space of Dissed is with loss of fenestrations in the sinusoidal endothelial cells accompanied by hepatocytes hypoperfusion w’ increased liver damage.
Fate/ Effects
1. Classic case: complete recovery 2. Cases with diffuse necrosis:
death 70-‐90% 3. Chronicity that may progress to
cirrhosis 4. Chronic carriers in whom the
viral antigens are excess in hepatocytes and may reach the blood
5. Post – necrotic scarring may result in: PH, LCF, jaundice and increased risk of HCC
Effects 1. Loss of hepatocytes + disruption of portal
circulation leading to Ø Hepatocellular failure
2. Obstruction of portal circulation leading to Ø Portal hypertension
3. Liver cell hyperplasia leading to Ø Hepatocellular carcinoma
N/E Liver slightly enlarged Surface may be smooth or nodular
Size: shrunken (except in biliary cirrhosis) Consistency: firm Outer surface & cut surface: nodular -‐ Micro: less than 3mm -‐ Macro -‐ Mixed Color : sometimes indicate cause -‐ Yellow: nutritional cirrhosis -‐ Green: nutritional cirrhosis -‐ Red: congestion -‐ Dark brown: hemochromatosis
M/E Range from mild to severe according to
Grade: degree of inflammation a. Piecemeal necrosis b. Lobular necrosis c. Lobular inflammation d. Portal inflammation
Stage: extent of fibrosis
a. Portal fibrosis b. Portal and periportal fibrosis c. Septal fibrosis d. Bridging fibrosis e. Incomplete cirrhosis f. Cirrhosis
• Loss of normal hepatic architecture: replacement by regenerative nodules surrounded by fibrous tissue septa
• The regenerative nodules: the regenerative hepatocytes may be small, large, uni or binucleated
• The fibrous tissue septa: it replace the damaged hepatocytes and develops at certain site, eg: perivenular, perisinusoidal, pericellular and in relation to portal tracts. The fibrous septa contains proliferating bile ductules and chronic inflammatory cells
Hepatitis Pathological types Classic acute viral hepatitis
Acute viral hepatitis with diffuse necrosis (fulminant viral hepatitis) Clinical course 1. Incubation period
2. Pre – icteric phase: non specific constitutional symptoms a. Serum sickness like symptom b. Urtecaria, skin rash c. Arthiritis, glomerulonephritis
3. Icteric phase: jaundice, dark urine, light colored stool & pruritis 4. Convalescence stage: for few weeks
n/b of cirrhosis Major source of excess collagen in cirrhosis is the peri – sinusoidal stellate cells w’ is activated by the following factors
a. Activated Von Kupffer cell, endothelial cells, hepatocytes and inflammatory cells b. PDGF stimulates stellate cell proliferation c. TNF is a potent stimulant of stellate cells to change to myofibroblastic phenotype d. TGF-‐β stimulates stellate cells to secrete the ECM (fibrogenesis)
Classic acute viral hepatitis Incidence common and the same irrespective of causative agent
Fate Recovery is common N/E Slightly enlarged
Shows red (congested) areas and green (cholestatic) areas
M/E
Hepatocytes shows -‐ Ballooning degeneration -‐ Feathery degeneration (foamy cytoplasm with droplets of bile) -‐ Fatty change (with HCV) -‐ Apoptosis and councilman bodies -‐ Focal spotty nectosis -‐ Many hepatocytes are normal Inflammatory cells (macrophages and lymphocytes) -‐ In portal tracts and around the necrotic foci Acute cholestatasis: due to
a. Obstruction of bile canaliculi by swollen, degenerated hepatocytes b. Bile canaliculi above the obstruction are dilated and filled with bile. It may from bile plugs or thrombi c. Cholangiolitis ( inflammation of intralobular bile canaliniculi )
♣ Intracytoplasmic bile droplets accumulate in hepatocytes (feathery degeneration) and in Von Kupferr cells
Recovery -‐ Active Von Kupffer cells show hypertrophy and hyperplasia with increased phagocytosis -‐ There’s increased inflammatory cells
Hepatitis B virus (HBV) Structure Dane particle formed of DNA core covered by a lipoprotein coat
Mode of infection Parentral Sexual Vertical transmission
Age All ages are affected Incubation period 8-‐12 weeks Clinical picture Severe à recovery within 3-‐4 months
1. Chronic hepatitis • Found in 5% of patients • Indicated by hepatocytes having HBs Ag 6 months after the onset of the disease
2. Carrier state • 5% of cases • Their hepatocytes have ground glass cytoplasm and sanded nuclei
3. Hepatocellular carcinoma 4. Death: 10-‐20% due to panacinar necrosis
Hepatocellular failure Definition It is the ultimate fate of many liver diseases. It may be either acute or chronic
Sign , symptoms 1. Jaundice : hepatotoxic 2. Hepatic encephalopathy 3. Coagulation defects
-‐ Defective hepatic synthesis of clotting factors (prothrombin, factors VII, IX, and X. abonormal factors are produced)
-‐ Thrombocytopenia due to splenomegaly -‐ DIC due massive liver cell necrosis
4. Acute liver failure: fever and foeter hepaticus 5. Hypoproteinemia 6. Vitamin deficiency: vit A,K,B12, folic acid 7. Hypoglycemia: defects in CHO metabolism 8. Hormone disturbance 9. Hepatorenal failure 10. Chronic liver failure
-‐ Ascites and edema -‐ Hypothermia -‐ Hyperesternism
Hepatic encephalopathy Patho Results from inability of the liver to detoxify the neurotoxic nitrogenous bacterial products of the gut
(ammonia) w’ is absorbed, cross the portal to systemic circulation to reach the brain where it impairs neuronal functions and promotes generalized brain edema
Causes -‐ Massive liver cell damage -‐ Increased nitrogenous load due to high protein diet or GIT hemorrhage -‐ Porto – systemic anastomosis especially porto – caval. In this case, portal blood passes to the
hepatic vein prior to its detoxification in the liver Raised blood
ammonia level results in
• Psychiatric disturbance • Flabby tremors • Disturbance of consciousness • Coma and death
Hyperestrenism Cause Due to failure of estrogen degradation in the liver
Leads to a. Hypogonadism in both sexes b. Palmer erythema due to local vasodilatation of blood vessels of the skin of the palms of the hands c. Spider angiomas consisting of a central pulsating dilated arteriole from w’ small vessels radiate. They are found
in the skin of the face, neck and arms (areas drained by the superior vena cava) d. Testicular atrophy and gynaecomastia in males e. Menstrual irregularities, secondary amenorrhea and breast atrophy in females
Portal hypertension Definition Elevation of the portal venous pressure than normal ( N=7mmHg) Causes Pre-‐sinusoidal
1. Massive splenomegaly 2. Portal vein obstruction 3. Portal venular obstruction (fibrosis,
bilharziasis)
Sinusoidal 1. Cirrhosis
Post-‐sinusoidal 1. Veno-‐occlusive disease 2. Budd-‐Chiarri syndrome 3. Obstruction of major hepatic veins by tumor 4. RSHF and constrictive pericarditis
Effects 1. Ascites -‐ Definition: intra-‐peritoneal accumulation of transudate -‐ Causes:
a. Increased hydrostatic pressure in portal circualtaion b. Decreased osmotic pressure due to decrease albumin synthesis by the liver c. Na and water retention due to 2ry hyperaldosteronism and ADH secretion d. Leakage of hepatic lymph through hepatic capsule due to hepatic vein obstruction
2. Splenomegaly -‐ Due to chronic venous congestion. May lead to hypersplenism (splenomegaly and pancytopenia)
3. Varices -‐ Leads to esophageal varices, caput medusa ( varicosities of periumbilical veins ) , piles ( ano-‐rectal varices )
Pathology of shistosomiasis
Species S. Haematobium S. Mansoni S. Japonicum
Life cycle
1. Egg from host 2. Egg hatch release meracidia to water 3. Miracidia penetrate snail tissue 4. Miracidia is safely in sporocycst of snail (successive generation) 5. Cercaria released by snail into water and freely swimming (this is infective stage) 6. Cercaria penetrate the skin ( diagnostic stage) 7. Cercaria loses it tails during penetration and become shistosomulae 8. Shistosomulae will reach the circulation 9. It will migrate to portal blood in liver and mature into adults 10. Paired adult worm migrate to
-‐ Mesenteric venule of bowel/rectum (SH) à laying eggs that circulate to liver and shed in stools -‐ Venules plexus of bladder / urogenital plexus (SM)
Early tissue reaction
♣ Cercaria penetrate skin à rash called shistosome or swimmer’s itch ♣ Eggs laid in target organs release antigen à cause Katayama fever ♣ Fever ♣ Urticarial ♣ Malaise ♣ Diarrhea
=hypersensitivity 1
Late tissue reaction
Granulomatous inflammatory reaction -‐ inflammatory cell, macrophages, foreign
body, giant cell, lymphocyte, plasma cell and esinophils
Granulation tissue -‐ Newly formed blood vessels called angiomatoid
reaction and fibroblasts which mediates collagen deposition and fibrosis
Focal reacation -‐ Colon -‐ SM -‐ Morderate amount of ova -‐ Focal reaction forming a bilharzial nodule
Diffuse reaction -‐ Bladder -‐ SH -‐ Heavy deposition of ova -‐ Diffuse inflammatory reaction
1. Lesion of hollow organs 2. Bilharzial hepatic fibrosis
3. Bilharzial splenomegaly 4. Pulmonary bilharziasis
Lesion of hollow organ
1. Hemorrhagic spot caused by penetration of venules by ova 2. Congestion & edema caused by associated inflammatory cells 3. Granularitycaused by bilharzial inflammatory cells aggregates 4. Polyps 5. Sandy patches 6. Ulcers and erosion 7. Secondary bacterial infection 8. Closed lesion
Bilharzial cystitis Intestinal bilharziasis Hepatic bilharziasis Site Trigone Rectum Liver (portal tract)
Shistosoma Hematoium Mansoni Mansoni Characteristic Polyps are few in number
Sandy patches are common Linear fissure ulcer Contracted ladder Epithelial changes due to bilharzial reaction and secondary bacterial infection
Polyps are numerous Ulceration Sandy patches are not common Fissure ulcers are asent In closed lesion, pericolic mass Intestinal lumen is rarely narrowed
Diffuse hepatic periportal fibrosis Embbboli of ova and worms form the intestinal venous plexus induce an inflammatory reaction that ends with fibrosis Fibrosis not cirrhosis Not related to HCC
Epithelial changes /
pathogenesis
Hyperplasia Von Brunn’s nest Cystitis cystica Cystitis glandularis Ulcer Atrophy Squamous metaplasia Leukoplakia Squamous cell carcinoma
Pathogenesis Ova: venular and perivenular bilharzial reaction then fibrosis Worms: washed by the portal circulation to be impacted in the portal tracts Portal tracts: fibrosis, vascular and bile ductular proliferation Toxin: mild fatty change Kuppfer cells: dark brown pigment
Complication Anemia Obstructive uropathy Stone formation Carcinoma Pulmonary bilharziasis
Bilharzial hepatic fibrosis Microcytic hypochromic anemia Bilharzial dysentery Fibrosis stenosis is rare No relation to malignancy No malabsorption syndrome
Polyps : more common in colon
N/E M/E Small polyps is sessile and simple Large pedunculated and compound Soft with gritty sensation Mucosa in between is intact or ulceration
Core of connective tissue containing bilharzial reaction Mucosa maybe intact, hyperplastic or ulcerated
Sand patches More common in UB Mechanism : heavy deposition of ova caused which are dead and calcified à compressed blood vessels à leads to atrophy of overlying epithelium à appear as calcified ova shine through mucosa
N/E M/E Circumscribed, raised patch, rough, and dirty yellow ( wet sea sand ) Gritty sensation
Calcified ova with minimal or no bilharzial reaction fibrosis, mucosa is atrophied and maybe ulcerated
Ulcer Pathogenesis N/E 1. Passage of ova
2. Fissure of ulcer (linear) 3. Tip of a polyp 4. Twisting of polyp 5. Secondary to bacterial infection 6. Allergic necrosis 7. Over a sandy patches
1. Single or multiple 2. Small or large 3. Superficial or deep 4. Irregular margin 5. Sharp edge (wall of ulcer) 6. Granular floor 7. Indurated base
Closed lesion Severe fibrosis Closed lesion Contracted organ with obstructive syndromes Pericolic or perivesical mass Parasitic emboli liver and pulmonary bilharziasis
Failure of egg to go outside of body Cause intense fibrosis to deposit the trapped eggs Eggs will provoke granuloma reaction Eggs will go to other organ to infect
Epithelial changes in bilharzial cystitis Cystitis cystica Cystitis glandularis Squamous metaplasia Leukoplakia
Large size Lined by 1-‐2 layer of flat cell Contain watery secretion It is due to 2ry infection Not precancerous
Small size Lined by 1-‐2 layers of columnar cell Contain mucus It is due to metaplasia It is precancerous
Change of transitional epithelium to stratified squamous epithelium It is precancerous
A white patch on mucosa of UB It is formed of keratinized stratified squamous epithelium It is precancerous
Granulation tissue of hepatic bilharziasis Fine Coarse
Small portal tracts Less than 50%
Mild or moderate Few ova, no worm
Size decrease Fine granular
Large portal tracts More than 50%
Severe Many ova, or worm
Marked decrease in size Coarsely irregular
Portal hypertension Definition Increase resistance more than 7mmHg in portal vein Causes Pre hepatic
-‐ Thrombosis of portal vein -‐ Congenital atresia/stenosis -‐ Extrinsic compression
Hepatic -‐ Cirrhosis -‐ Shistosomiasis
Post hepatic -‐ Hepatic vein thrombosis -‐ Cardiac disease
Pathogenesis Vascular lesion
Pressure by fibrosis Intrahepatic porto – systemic anastomosis Extrahepatic portal and splenic vein thrombosis
Manifestations Ascites Caput medusa Esophageal varices Haemorrhoids Splenomegaly
Early splenomegaly Late splenomegaly Cause REC Hyperplasia in response to B antigen Portal hypertension (splenic congestin) Size Slightly increase (2x) Huge increase (10x)
Capsule Stretched Thick and whitish adherent Subscapular hemorrhage
ME Follicle hyperplasia Congested red pulp excess esinophils
Lymphoid follicle atrophy Prominent red pulp Fibrosidrotic nodules
Splenic vein Normal Dilated Hypersplenism Absent Present à active destruction of blood cells
and platelets Effects of
splenomegaly Compression Hypersplenism Irregular fever
Egyptian splenomegaly Pulmonary bilharziasis Intestinal bilharziasis Hepatic fibrosis Splenomegaly Anemia Leucopenia Irregular fever
May occur with SH Cercariae bronchopneumonia Ova lesions à vascular lesions & intestinal lesions Worm lesions à verminous pneumonia Effects : -‐pulmonary hypertension ( cor pulmonale) -‐pulmonary aneurysm: dilatation of pul. Artery
Diabetic nephropathy Lesions
encountered 1. Glomerular lesions 2. Renal vascular lesions mainly artherosclerosis 3. Pyelonephritis, including necrotizing papillitis
Risk factors ♣ DM Type & duration Ø 20% of type 1 after 20 years Ø 40% of type II any duration
♣ Poor diabetic control ♣ Hypertension ♣ Smokers ♣ Family history
Stage I (Very early diabetes) 1. Increased demand à increased GFR 2. Hyperglycemia leads to increased kidney filtration ( osmotic load and toxic effects of high sugar
levels on kidney cells ) 3. Enlarged kidneys
Stage II (developing diabetes : clinically silent phase) 1. Continued hyper filtration and hypertrophy 2. GFR remains elevated or returned to normal 3. Glomerular damage progress to significant microalbuminuria (small but above normal level of
the protein albumin in the urine) 4. Significant microalbuminuria will progress to end stage renal disease (ESRD). All diabetes
patients should be screened for microalbuminuria on a routine basis Stage III (overt or dipistick-‐positive diabetes)
1. Glomerular damage has progressed to clinical albuminuria 2. BM thickening due to AGEP 3. The urine is ‘’dipstick positive’’, containing more than 300mg o f albumin in a 24 hour period 4. Hypertension typically develops during stage 3
Stage IV (late stage diabetes) 1. Glomerular damage continues, with increased protein albumin in the urine 2. Kidney’s filtering ability began to decline 3. Steadily BUN and creatinine began to increase 4. GFR decreases about 10% annually. Almost all patients have hypertension at this stage.
Stage V (end stage renal disease, ESRD) 1. GFR has fallen to
Diabetic nephropathy effects GHF Glomerular hyper filtration
-‐ Glucose provides an osmotic diuretic effect result is increased renal filtration leading to glomerular hypertrophy
-‐ Glomerular pressure increases -‐ Kidney responds with hypertrophy of epithelium and endothelium -‐ Accelerates glomerular cell failure -‐ Result is premeature glomerulosclerosis
Metabolic changes Oxidant stress -‐ Related to glomerular hypertrophy and abnormal metabolism Non enzymatic glycosylation of macromolecules -‐ Particularly basement membrane à increased type IV collagen & decreased proteoglycans -‐ Both changes decrease the permeability of capillaries and disturb leucocyte diapedesis,
oxygen diffusion, nutrition and metabolic waste removal Activation of glucose metabolizing enzymes
Hormonal imbalance 1. Insulin deficiency 2. Elevated glucagon concentrations 3. Increased transforming growth factor (TGF-‐β) 4. Increased angiotensin II 5. Abnormally regulated thromboxanes and endothelins 6. Abnormal insulin like growth factor (IGF)-‐1 7. Elevated platelet derived growth factor (PGDF)
Histologic change 1. Mesangial expansion
2. GBM thickening throughout their entire length 3. Glomerular sclerosis due to intraglomerular HTN (renal VD and ischemic injury induced
by hyaline narrowing of the vessels supplying the glomeruli) In many advanced cases, there is also nodular glomerulosclerosis (Kimmelstiel-‐Wilson lesion) with round masses of GBM mesangial matrix material in the glomerular tufts. This histologic picture is highly characteristic of diabetes and it is usually present if the diabetes has been present for longer than 20 years ( sometimes much less)
Role of TGF-‐β 1. Stimulates ECM synthesis by increases ECM proteins 2. Inhibits ECM degradation 3. Up regulates protease inihibitors; down regulates matrix degrading enzymes 4. Stimulates synthesis of integrins (matrix receptor) 5. Key role in glomerular and tubuloepithelial hypertrophy, basement membrane thickening, and mesangial matrix
exoansion 6. Stimulates production of several growth factors (basic fibroblast growth factor, platelet derived growth factor)
that stimulates formation of ECM synthesis
Nephrotic syndrome Nephritic syndrome Rapid progressive glomerulonephritis
Chronic glomerulonephritis
Patho Wall of glomerular capillary esp the BM leading to increased permeability to plasma proteins
Damage of the glomerular capillary wall with decreased filtration and escape of red cells with urine
Epithelial proliferation of the parietal layer of Bowman’s capsule forming crescents
It is the end stage of most glomerular disease
C/P or characteris
tics
a. Proteinuria (>3-‐5g/day) b. Hypoproteinemia() d. Contains RBC and
pus cells e. Urinary casts mainly
red cell case, less common à hyaline, granular and epithelial
If it is severe, rapid onset of a. Hematuria b. Oliguria or anuria c. Hypertension d. Variable
proteinuria and edema
Characteristics 1. Moderate hypertension 2. Hypertensive retinopathy 3. Increase blood urea and
creatinin 4. Normocytic anemia
Cause Primary glomerular diseases -‐ Foot process disease -‐ Minimal change
glomerulopathy -‐ Focal segmental
glomerulosclerosis -‐ Membranous
glomerulopathy -‐ Membrano proliferative
glomerulonephritis
Primary glomerular disease -‐ Acute diffuse
proliferative (post strep) glomerulonephritis
Secondary glomerular disease -‐ Amyloidosis -‐ Diabetic glomerular disease -‐ SLE -‐ Drugs -‐ Infections -‐ Malignancy
Secondary glomerular disease -‐ SLE
N/E -‐ Kidney is contracted -‐ Firm -‐ Adherent capsule -‐ Finely granular surface with
small cyst -‐ Cortex and medulla are not
demarcated
M/E -‐ Glomeruli: some are fibrosed and hyalinized and others show compensatory hypertrophy
-‐ Tubules: atrophy -‐ Interstiitum: interstitial
fibrosis and chronic inflammatory cellular infiltration
-‐ Blood vessels: hypertensive changes
Membranous glomerulonephritis Explanation M/E
Most common cause of nephrotic syndrome in adults There is thickening of the basement membrane with subepithelial deposits of IgG and C3 and fusion of the epithelial foot processes
Minimal change GN Explanation E/M
Most common cause of nephrotic syndrome in children No changes by ordinary microscope By EM there is fusion of foot processes of podocytes
Kidney failure Causes Renal (1ry renal disease)
-‐ Congenital -‐ Acquired (glomerular/
tubulointerstitial)
Pre-‐renal (inadequate blood supply)
-‐ Heart failure – low cop -‐ Low renal perfusion -‐ Volume depletion -‐ Sepsis -‐ Severe bleeding
Post-‐renal(bilateral blood supply) -‐ Tumors, BPH (prostate)
ARF Is the sudden and severe reduction in previously normal renal function, may result from primary renal disease. Frequently have: metabolic acidosis, hyperkalemia, disturbance in body fluid homeostasis, 2ry effects on other organ system
CRF Is the gradual and progressive reduction in renal function. Failure may occur over weeks, months or years Effects Cardiopulmonary
a. High blood pressure with its problems b. Fibrinous pericaridits c. Accelerated atherosclerosis
GIT
a. Nausea and vomit b. GI bleeding – uremic gastritis, pinpoint bleeding in the stomach mucosa, uremic colitis c. Poor appetite and altered sense of smell d. Alterations in sense of taste ( low serum zinc) e. Pancreatitis
Bones Renal osteodystrophy that includes
a. Secondary hyperparathyroidism, with loss of calcium and eventually collagen from bones b. Osteomalacia (increase in unmineralized osteoid) mostly refractory to vit D ttt
Prostatic disease Inflammation Prostatic hyperplasia Neoplasia
Prostatic hyperplasia General features When sufficiently large, the nodules compress and narrow the urethral canal cause partial or
sometimes virtually complete obstruction of the urethra. It is not a premalignant lesion Etiopathogenesis 1. Under effect of a metabolite of testosterone ; DHT (ultimate mediator of prostatic enlargement)
♣ Stromal cells of prostate synthesized DHT à bind to nuclear androgen receptor and signal the transcription of growth factorà cause autocrine and paracrine effect on stromal cell and nearby epithelial cells à prostatic enlargement
2. Increase in estradiol level ♣ Estrogen induce in increase in androgen receptors à cells more liable to DHT
3. Heterogeniety of the disease
N/E ♣ Overall, gland is enlarged ♣ May reaching massive size ♣ Firm, rubbery in consistency ♣ Small odules are present throughout the gland, usually 0.5-‐1 cm in diameter but sometimes
much larger ♣ Some of the larger nodules show cystic change
M/E ♣ Glands are composed of a variable mixture of hyperplastic glandular elements and
hyperplastic stromal muscle ♣ The glands are larger than normal, variable in size and shape and lined by tall epithelium
that is frequently thrown into papillary projections ♣ The acini may contain numerous corpora amylacea
Clinical features Mainly obstructive symptoms due to
1. The hyperplastic nodules compress and elongate the prostatic urethra, distorting its course 2. Involvement of the peri-‐urethral zone at the internal urethral meatus interferes with the
sphinter mechanism
Consequences 1. Continued obstruction of the bladder outflow results in gradual hypertrophy of the bladder musculature
2. Trabeculation of the bladder wall develops due to prominent bands of thickened smooth muscle between which diverticula may protrude
3. Dilatation of the bladder occurs when the compensatory mechanism fails, this results in ♣ The ureters gradually dilated hydroureter allowing reflux of urine ♣ If untreated, bilateral hydronephrosis may develop, with dilatation of renal pelvis and
calyces ♣ Repeated infections predispose to the development of calculi often containing
development of calculi often containing phosphates, within the bladder ♣ Urinary incontinence
Complications 1. Bladder stones / lithiasis 2. UTI 3. Hematuria 4. Acute urinary retention 5. Bladder decompensation 6. Urinary incontinence 7. Upper urinary tract deterioration and
azotemia
8. Obstructive uropathy 9. Bladder hyperthrophy 10. Trabeculation 11. Diverticula formation 12. Hydroureter – bilateral 13. Secondary infection
Carcinoma prostate General features Age: the tumor is rare 50y.o
Risk factors 1. Endocrinologic factors: androgens 2. Racial factors: more common in aftrican 3. Environmental factors: high fat diet, exposure to polycyclic aromatic hydrocarbons 4. Genetic basis: familial cases ( ch 1 and 10 )
Etiopathogenesis PIN ♣ Definition: prostatic intraepithelial neoplasia
♣ Is a precursor lesion sugest that prostatic carcinoma may also be present. ♣ Consist of intra acinar proliferation of cells that demonstrate nuclear anaplasia foundin a single
acinus or small group of prostatic acini
Presenting features
1. Clinically silent and latent carcinoma: unexpected finding in autopsy 2. Incidental carcinoma: in 15-‐20% of TURP done for BPH 3. Clinical carcinoma: detected by PR, other investigations and is symptomatic 4. Occult carcinoma: presents with features of metastases but primary is not evident
N/E ♣ Peripheral zone in the posterior lobe of the gland
♣ Palpable in PR ♣ Multifocal, gritty and firm
M/E Back to back arrangement of the malignant glands, lining cells show prominent nucleoli
Invasion of stroma and perineural spaces
Grading Gleason grades (scores): based on the degree of differentiation among the cells
1 Small nodules of uniform glands, tightly packed 2 Glands show various shapes and sizes, closely packed 3 Glands with packed variation in size and shape, infiltrating normal prostatic tissue 4 Large, irregular, fused glands 5 No obvious glands, solid sheets of tumor cells spreading through prostatic tissue
Spread 1. Local spread: tends to invade nerves, seminal vesicles and adjacent pelvic organs ( local extension)
2. Lymphatic spreads: to para-‐aortic, iliac LN 3. Hematogenous metastates: most often found in the vertebrae & sacrum ; can also occur in
kidneys, lungs and brain 4. Bony metastases are often osteoblastic and are associated with elevated serum alkaline
phosphatase
Diagnosis 1. Digital rectal examination 2. Diagnostic imaging 3. Cystoscopy 4. Chemical pathology 5. Biopsy