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This study guide was prepared by Fanconi.
THE GASTROINTESTINAL TRACT Esophagus · Dysphagia = difficulty swallowing · Heartburn = retrosternal burning pain · Hematemesis = vomiting of blood · Anatomic Anomalies o Atresia and fistulas § Most common = proximal esophagus ends in a blind pouch while the distal segment communicates with the trachea o Stenosis, webs, and rings § Stenosis = congenital or acquired § Webs = upper esophagus, smooth ledges of mucosa § Rings = Schatzki rings at gastroesophageal junction o Lesions Associated with Motor Dysfunction § Achalasia · Aperistalsis of esophagus · Relaxation of LES with swallowing · Increased resting tone of LES o Proximal esophageal dilation o Dysphagia o Regurgitation o Young adults o 2-7% carcinoma risk · Diminished myenteric ganglia · Thickened or thinned muscular wall · Secondary muscosal damage § Secondary Achalasia · Chagas dz = Trypanosoma cruzi · Disorders of vagal motor nuclei = polio, surgerical ablation · Diabetic autonomic neuropathy · Infiltrative disorders = malignancy, amyloidosis, sarcoidosis § Hiatal Hernia · Saclike dilation of stomach through protrusion above diaphragm, separation of diagrphragmatic crura · Sliding (axial) = 90%, short esophagus with traction on the stomach · Paraesophageal (rolling) = cardia of stomach dissects alongside esophagus into thorax, leading to strangulation and infarction § Diverticula · Pharyngeal (Zenker) = upper esophagus, the result of motor dysfn · Traction = more distal, from fibrosing mediastinal process or abnormal motility § Laceractions · Mallory-Weiss syndomre · Longitudinal tears in esophagus at esophagogastric junction · Assoc. with excessive vomiting, alcoholics · 5-10% of upper GI bleeding events o Esophagitis § Reflux Esophagitis · Reflux of gastric contents most common cause · Hyperemia and edema · Thickening of basal zone and thinning of superficial layers of stratified sq. epith. · PMN or eosinophilic infiltrate · Superficial necrosis and ulceration with adherent inflammatory exudates § Barret Esophagus · Replacement if normal distal esophagus epithelium with metaplastic columnar epithelium · Respose to prolonged injury · Pluripotent stem cells, in setting of lower pH, differentiate into more resistant types of epithelium · Red, velvety mucosa, irregular circumferential band at GEJ · Risk of adenocarcinoma 30X § Infectious and Chemical Esophagitis o Varices § 90% of cirrhotic pts, esp. alcoholics § Hepatic schistosomiasis § Severe portal HTN induces formation of collateral bypass channels · Rectal canal = hemorrhoids · Falciform ligament = caput medusa § Tortuous dilated veins within submucosa § 40% mortality with each episode of bleeding § 90% chance of recurrence/yr with survivors · Tumors o Benign Tumors § Intramural or submucosal = leiomyoma, fibroma, lipoma hemangioma, neurofibroma… § Mucosal = squamous papilloma, fibrovascular polyp, inflammatory polyp o Malignant Tumors § Squamous cell CA of esophagus = China, Iran, Russia, S. Africa · Dietary factors, · Lifestyle (alcohol, tobacco, urban) · Esophageal disorders · Predisposing Influences (celiac dz) · Most = middle 1/3 of esophagus · Most = polypoid § Adenocarcinoma = ˝ of esophageal cancers · Assoc. with Barret tmucosa · Overexpression of p53 · Loss of 17p · Most are distal 1/3 of esophagus · Signet ring cells · 5 yr. Survival < 30%
Stomach · Congenital Anomalies o Pancreatic Heterotopia · In gastic muscle wall o Diaphragmatic hernia · Stomach displaced into thorax, pulmonary hypoplasia o Pyloric Stenosis · Congenital = hypertrophy of muscularis propria · Male 4 : Female 1 · Acquired = complication of antral gastritis or malignancy · Gastritis o Acute Gastritis · NSAID use, alcohol, smoking, CA chemo, uremia, systemic infection, severe stress, ischemia and shock, ingestion of acid or alkali, radiation, trauma · Increased acid production, decreased bicarb buffer, disruption of mucus layer, sloughing of epithelium, hemorrhage o Chronic Gastritis · Mucosal atrophy and epithelial metaplasia · H. pylori infection · Immunologic = antibodies to parietal cells · Alcohol, tobacco o H. pylori · S-shaped GNR · Special traits = motility via flagella, elaboration of urease, buffering gastric acid, and binding to surface epithelial cells via adhesin · Some strains express cagA and vacA cytotoxins = proinflammatory peptides. · Strong assoc. with chronic gastritis and PUD · Possible assoc. with gastric carcinoma and lymphoma o Autoimmune Gastritis · Less than 10% chronic gastritis · Abs to gastric parietal cells and intrinsic factor · Assoc. with Hastimoto thyroiditis and Addison dz · Gastric hypochlorhydria and serum hypergastrinemia · 2-4% CA risk · Peptic Ulcer Disease o Peptic Ulcers · Usually solitary · 10% Am. men, 4% Am. women · NO genetic tendencies · Duodenal ulcer more common with · Alcoholic cirrhosis, COPD, CRF, hyperparathyroidism · 4 duodenum : 1 stomach · Ulcer promotion = gastric hyperacidity, NSAIDS chronic use, smoking, alcohol, corticosteroids, hypercalcemia · Microscopic appearance · Superficial necrotic debris · Zone of inflammation · Granulation tissue · Scar o Acute Gastric Ulceration · Curling ulcers = shock, burns, trauma · Cushing ulcers = ICP as in trauma or surgery · Impaired oxygenation, stimulation of vagal nuclei with hypersecretion of gastric acid, systemic acidosis · 5-10% of ICU patients, correct the underlying condition to treat o Bezoars = luminal concretions of indigestible material o Hypertrophic Gastropathy · Cerebriform enlargement of gastric rugal folds · Hyperplasia of mucosal epithelial cells · Menetrier dz = hyperplasia of surface mucosal cells · Hypertrophy-hypersecretory gastropathy = hyperplasia of parietal and chief cells · Gastric gland hyperplasia = secondary to gastrin secretion by gastrinoma · Excess secreted protein may cause hypoalbuminemia and protein-losing gastroenteropathy · Risk of adenoCA o Gastric Varices · Portal HTN · Less common than esophageal · Tumors o Benign Tumors · 90% gastric polyps are hyperplastic or inflammatory, no malignant potential · Gastric adenoma = true neoplasm · Dysplastic epithelium · Incidence with age · Background of chronic gastritis or familial polyposis syndromes o Gastric Carcinoma · 90-95% carcinoma · Incidence decreased 4-fold in past 60 yrs · Environmental influences · Host = H. pylori, autoimmune gastritis, partial gastrectomy permitting gastroduodenal reflux · Telomerase, c-met, K-sam, erb (growth factor receptor systems) · Most around pylorus and antru, · Intestinal = polypoid expansile growth · Difffuse = single signet ring cells, no change in incidence, linitis plastica = rigid, thickened stomach · Dissemination to ovaries = Krukenberg tumors o Less Common Gastric Tumors · Lymphomas = 5% gastric malignancies
Small and Large Intestines · Congenital Anomalies o Duplication, malrotation, emphalocele (musculature fails to form), gastroschisis (portion of abdominal wall fails to develop altogether) o Atresia and Stenosis · Intrauterine vascular accidents, intussusception, duodenum most commonly affected · Failure of cloacal diagraphm to rupture leads to imperforate anus o Meckel Diverticulum · Persistence of vitelline duct (connects yolk sac with gut lumen) · 30 cm from ileocecal valve · 2% normal popuation o Congenital Aganglionic Megacolon = Hirschsprung dz · Arrested migration of neural crest cells into gut · Aganglionic segment with obstruction · Assoc. with Down syndrome · Acquired megacolon in Chagas’ dz · Enterocolitis o Diarrhea and Dystentery · Dysentery is low-volume, painful diarrhea · Diarrhea = secretory, osmotic, exudative, deranged motility, malabsorption o Infectious Enterocolitis · Viral · Rotavirus gp A = dsDNA, 6-24 month old infants · Adenoviruses = dsDNA, kids < 2 · Astroviruses = ssRNA, kids, water, cold foods, raw shellfish · Norwalk = ssRNA, school-age kids to adults · Small intestine shows modestly shortened villi, lamina propria inflammation, damage to surface cells · Bacterial · Preformed toxin, toxigenic organisms, enteroinvasive organisms · Enterotoxins = secretagogues (stimulate fluid secretion) and cytotoxins (epithelial cell necrosis). E. coli produce both forms of toxins · Salmonella = ileum and colon, S. typhimurium causes typhoid fever (biliary tree, bones, joints meninges) · Shigella = colonic inflammation, erosion, exudates · C. jejuni = · Y. enterocolitica, pseudotuberculosis = necrotizing granulomas · V. cholerae = normal small intestine · C. perfringens = necrotizing enterocolitis · E. coli = cholera-like toxin, enterohemorhhagic causes shiga-like toxin · Necrotizing enterocolitis = low-birth-weight or premature neonates · Antibiotic associated colitis = pseudomenmbranous colitis (C. difficile), toxin detectable in stool o Collagenous and Lymphocytic Colitis · Chronic watery diarrhea in older women · Both benign (lymph. assoc. with celiac sprue) o Misc. Intestinal Inflammatory Disorders · Nematodes · Flatworms · Protozoa · In AIDS = microsporidia, cryptosporidia, Isospora belli · Transplantation · Drug-induced (esp. NSAIDS) · Radiation · Neutropenic colitis = typhilitis · Diversion colitis = after surgery · Malabsorption Syndromes o Celiac Sprue · Gluten-sensitive enteropathy (gliadin protein) · 90-95% patients express DQw2 and HLA B8 · Cross-reactivity to type 12 adenovirus · Severity decreases in proximal-to-distal intestin · 10-15% risk of T cell GI lymphoma o Tropical Sprue · Brunt of damage is distal, compared to celiac dz · More eosinophils than celiac · Enterotoxigenic E. coli o Whipple Disease · GI, CNS, joints · Tropheryma whippelii, gram-positive actinomycete · Distended macrophages in lamina propria, which contain bacilli · Absent inflammation · Responds to antibiotics o Disaccharidisase Deficiency · Lactose remains in lumen and exerts an osmotic pull, diarrhea and malabsorption · Acquired – N. America blacks · No abnormalities of mucosa o Abetalipoproteinemia · Autosomal recessive, can’t make apoproteins required for lipoprotein export form mucosal cells, TGs stored in cells cause lipid vacuolization · Burr cell appearance of RBCs · Low chylomicrons, VLDLs, and LDL · Presents in infancy with failure to thrive
· Idiopathic Inflammatory Bowel Disease o Crohn's Disease · Sharpy delimited and transmural inflammation · Noncaseating granulomas · Fissuring and fistula formation · Systemic manifestations · Ileum and colon · Skip lesions, creeping fat · Fat or vitamin malabsorption · Poor response to surgery o Ulcerative Colitis · Continuous inflammation proximally from rectum · No granulomas · Thin wall · Marked pseudopolyps · Good response to surgery o For CD and UC, no HLA types associated (?) · Vascular Disorders o Ischemic Bowel Disease · Arterial thrombosis = ASVD, vasculitis, hypercoagulable states · Arterial embolism = cardiac vegetations · Venous thrombosis = hypercoagulable states, cirrhosis, sepsis, trauma, neoplasms · Nonocclusive ischemia = cardiac failure, shock, dehydration · Transmural infarction more common in small bowel (completely dependent on mesenteric blood supply); large bowel has posterior abdominal wall collaterals o Angiodysplasia · Tortuous, abnl dilations of submucosal veins · LaPlace law = more often in cecum and ascending colon because of maximal wall tension because of greater diameter o Hemorrhoids · Variceal dilaation of anal and perianal submucosal venous plexuses · Diverticular Disease o Acquired divertoculosis in >50% of Americans > 60 yo o Occur alongside taeniae coli o Dissect into appendices epiploicae o Diverticulitis is a complication o Pathogenesis · Focal weakness in bowel wall at sites of penetrating blood vessels · Increased intraluminal pressure from exaggerated peristaltic contractions · Intestinal Obstruction o Hernias · Weakness or defect in the wall of peritoneal cavity permits protrusion of sac · Incarceration, strangulation o Adhesions · Localized peritoneal inflammation · Complications = internal herniation, obstruction, strangulation o Intussusception · Telescoping of one segment of intestine into immediately distal segment · Infants and kids = spontaneous and reversible · Adults = point of traction is usually a tumor o Volvulus · Twisting of bowel loop about its mesenteric base · Occurs most often in sigmoid colon · Tumors o Small Intestinal Neoplasms · Adenomas near ampulla of Vater, esp in polyposis syndromes o Tumors of the Colon and Rectum · Non-neoplastic polyps · Hyperplastic = found in ˝ of people > 60 · Juvenile = hamartomas · Peutz-Jeghers = syndrome of melanocytic pigmentation of mucosal and skin surfaces, increased risk of carcinomas · Adenomas · Epithelial proliferative dysplasia · Tubular · Villous · Tubulovillous o Risk of coexistent malignancy = polyp size, histologic architecture, severity of dysplasia · Familial syndromes · Familial adenomatous polyposis o AD, 5q21 o Prophylactic colectomy · Gardner syndrome o As above with osteomas, epidermal cysts, fibromatosis, abnormal dentition, higher frequency of duodenal and thyroid cancer · Turcot syndrome o Alimentary adenomas, CNS gliomas · APC gene = tumor-suppressor · HNPCC = faulty DNA proofreading · Loss of DNA methyl groups · K-ras gene mutation · Allelic loss on 18q, DCC = cell adhesion protein · Losses at 17p = p53 gene · Telomerase = expressed in cancers but not adenomas · Colorectal carcinoma · 98% adenocarcinomas · Most common sites = cecum/ascending colon and rectosigmoid colon · Polypoid or napkin-ring · Carcinoid tumors · Tumor of gut endocrine cell · Appendiceal, rectal carcinoids infrequently metastasize · Ileal, gastric, and colonic carcinoids are frequently aggressive · Yellow-tan tumors · Measure 5-HIAA in urine · GI lymphoma · Seen in chronic spruelike malabsorption syndromes, native of Mediterranean region, immunodeficiency states · B-cell lymphomas from MALT · Sprue-assoc = T-cell · Mediterranean = B-cell in kids · Mesenchymal tumors · Lipomas · Stromal tumors = spindle cell lesions · Kaposi sarcoma
Appendix · Acute Appendicitis o Most common abdominal condition requiring surgery o Periumbilical pain later localizing to RLL o Symptoms may be absent in very young and old o 20-25% false positive, 2% mortality untreated performation · Tumors of the Appendix o Mucocele o Mucinous cystadenoma = can rupture o Mucinous cystadenocarcinoma = jelly belly = psuedomyxoma peritonei
Peritoneum · Inflammation o Sterile peritonitis from bile spillage or pancreatic enzymes, endometriosis · Peritoneal Infection o Dull-gray membranes o Tuberculous = plastic exudates with myriad minute granulomas · Sclerosing Retroperitonitis o Dense fibromatous overgrowth of retroperitoneal tissues o Encroach on ureters = hydronephrosis o Methylsergide use for migraine headaches o Fibrosing disorders (mediastinal, sclerosing cholangitis, Riedel fibrosing thyroiditis) · Mesenteric Cysts o Sequestered lymphatics, pinched-off diverticula, congenital cysts of urogenital origin, walled-off infections · Tumors o Primary – rare mesothelioma o Secondary – common, diffuse seeding of surfaces
THE LOWER URINARY TRACT Ureters · Obstructive Lesions o Sclerosing Retroperitonitis § Begin of sacral promontory § Encircle lower abdominal aorta Urinary Bladder · Congenital Anomalies o Diverticula o Exstrophy = defect in anterior abdominal wall § adenocarcinoma risk · Inflammations o Acute and chronic cystitis o Interstitial cystitis = Hunner ulcer § Localized ulceration and inflammation of all layers of bladder wall § Chronic cystitis in women § Mast cells o Malakoplakia § Chronic bacterial cystitis § Targetoid intracellular structures ® Michaelis-Gutmann bodies = incompletely digested bacteria § E. coli most common causative organism § Cystitis glandularis and cystitis cystica · Intestinal metaplastia · adenocarcinoma risk · Neoplasms o Urothelial (transitional cell) tumors § 95% of bladder tumors § Factors in causation · Cigarette smoking · Industrial exposure to arylamines (esp. 2-naphthylamine) · Schostosoma haematobium infections (Egypt, Sudan) · Long term exposure to cyclophosphamide § 9p deletions ® tumor-suppressor gene p16 missing (inhibitor of cyclin-dependent kinase) § Deletions of 17p, in the region of p53 § 13q deletion, Rb gene § Tend to recur after excision
THE MALE URINARY TRACT Penis · Congenital Anomalies o Hypospadias, epispadias o Phimosis § abnormally small orifice in prepuce, often secondary to inflammation § Predisposes to infection and carcinoma · Inflammations o Nonspecific o Balanoposthitis = infection of glans · Tumors o Benign tumors § Condyloma acuminatum · HPV 6 and 11 · Sexual contact = mode of transmission · Koilocytosis (vacuolization of superficial epithelial cells) o Carcinoma in situ § Bowen disease · Men and women > 35 · Thickened gray-white plaque · Loss of normal surface maturation · Assoc with visceral malignancies § Erythroplasia of Queyrat · Shiny red velvety plaques on penis · No assoc. with visceral malignancies § Bowenoid papulosis · May mimic condyloma acuminatum grossly · Rarely evolves into invasive CA o Malignant tumors § SCC · incidence in uncircumcised · HPV 16, 18 · Mets to inguinal and iliac LN · Verrucous CA = giant condyloma = Buscke-Lowenstein tumor has low malignant potential Testis and Epydidymis · Congenital Anomalies o Cryptorchidism = 1% of 1 yo males o Failure of descent § Trisomy 13 § Hormonal abnormalities § Most cases are unilateral (75%) § Decr. Germ cell development, thickening and hyalinization of seminiferous tubules, sparing of Leydig cells § High prevalence of inguinal hernias, sterility, 5-10 fold increased in testicular neoplasms · Atrophy o Secondary o Primary in Klinefelter syndrome · Inflammations o Nonspecific epididymitis and orhcitis § Assoc. with infection of urinary tract § GNR § Chlamydia trachomatis and Neisseria gonorrhea in sexually active men < 35 § Leydig cells less severely affected o Granulomatous (autoimmune) orchitis § Unilateral testicular enlargement in middle aged men § Most be differentiated from tuberculosis o Gonorrhea § Retrograde extension of infection from urethra o Mumps § Orchitis one week after parotid inflammation § Not usually assoc. with sterility because it is unilateral and predominantly interstitial pattern of inflammation o Tuberculosis § Inflammation begins in epididymis § Granulomatous inflammation with caseous necrosis o Syphilis § Begins as orchitis in both congenital and acquired syphilis § Nodular gummas or diffuse interstitial inflammation · Vascular Disturbances o Torsion, with preexisting structural lesions · Testicular Tumors o Germ cell tumors § Seminoma · 50% of germ cell tumors · Peak incidence in 30s · Lobulated gray-white mass, no hemorrhage or necrosis · Abundant clear cytoplasm, large nuclei with prominent nucleoli · Human Chorionic Gonadotropin § Spermatocytic seminom · As above, but older patients · Indolent growths · Larger than classic seminoma § Embryonal Carcinoma · Peak in 20-30 · More aggressive than seminoma · Gray-white with hemorrhage and/or necrosis · With HCG and AFP both detected = mixed germ cell tumor with concomitant trophoblastic or yolk sac differentiation § Yolk sac tumor · Most common testicular neoplasam of infants and young children · AFP and a1-antitrypsin present within and around neoplastic cells · Good prognosis up to age 3 § Choriocarcinoma · Cytotrophoblastic + syncytiotrophoblastic elements · HCG · Dark nuclei in eosinophilic cytoplasm · Highly aggressive, small tumor size even with distant mets § Teratoma · Mature · Immature o Three germ layers · With malignant transformation o Usually carcinoma o Nongerminal tumors § Leydig (interstitial cell) tumors · Uncommon · Elaborate estrogens and / or testosterone · Homogenous, golden brown cut surface · Polygonal cells with eosinophilic cytoplasm and indistinct cell borders o Lipochrome pigment o Lipid droplets o Eosinophilc Reinke crystalloids § Sertoli cell tumors · Uncommon · May elaborate androgens · Most are benign § Testicular lymphomas · Most are diffuse large cell, non-Hodgkins lymphomas · Disseminate widely § Misc. lesions of tunica vaginals · Hydrocele · Hematocele · Chylocele · Spermatocele · Varicocele Prostate · Inflammations o Acute bacterial prostatitis § E. coli, Enterococcus, Staph aureus § Direct extension from urethra § Diagnosis based on urine culture o Chronic abacterial prostatitis § Most common § Sexually active men § Negative cultures despite leukocytes · Ureaplasma urealyticum, C. trachomatis · Nodular Hyperplasia o DHT mediates prostate growth (derived from T from 5a-reductase) o Nodules arise in periurethral area o Glands and fibromuscular stroma o Squamous metaplasia and infarcts o No relationship between nodular hyperplasia and prostatic CA · Carcinoma of Prostate o Familial susceptibility gene in white American men ® 1q24-25, 70% arise in peripheral prostate, esp. posterior region o Lymphatic mets in obturator nodes, OsteoBLASTIC mets to bones o Vast majority are adenocarcinomas, DNA ploidy = diploid is good o PSA bound to a1-antichymotrypsin good for differentiating prostatic CA from benign prostate diseases § % free PSA is lower in prostate cancer
THE KIDNEY Clinical Manifestations of Renal Disease · Acute nephritic syndrome = acute onset of grossly visible hematuria, mild-moderate proteinuria, and HTN (think post-strep GN) · Nephrotic syndrome = heavy proteinuria, hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria · Asymp. hematuria or proteinuria = manifestation of subtle glomerular dz · Acute renal failure = recent onset of azotemia with oliguria/anuria resulting from severe injury to one of the kidney’s compartments · Chronic renal failure = prolonged uremia · Renal tubular defects = polyuria, nocturia, and electrolyte disorders (metabolic acidosis). · UTIs · Nephrolithiasis = renal colic, hematuria, and recurrent stone formation
Renal Failure · Azotemia = BUN and creatinine, related to decr. GFR · Prerenal azotemia = hypoperfusion of kidneys · Postrenal azotemia = urinary outflow obstruction · Uremia = azotemia with constellation of symptoms (Table 20-1), sine quo non of chronic renal failure.
Congenital Diseases · Renal agenesis o Bilateral incompatible with life o Unilateral = compensatory hypertrophy of other kidney · Hypoplasia o Failure to develop to normal size, usu. Unilateral o No scars, reduced number of lobes and pyramids (<6) · Ectopic kidneys
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Above pelvic brim or within the pelvis · Horseshoe kidney o Fusion of upper and lower poles (usu. Lower – 90%), kidney continues across the midline anterior to great vessels
Cystic Diseases of the Kidney · Cystic Renal Dysplasia o Sporadic, nonfamilial o Abnormal metanephric differentiation o Obstructive abnormalities of ureter o Immature ducts, undifferentiated mesenchyme, focal cartilage formation · Autosomal Dominant Polycystic Kidney Disease o 10% of chronic renal failure, adults o PKD1 gene = 16p, 85% of cases § Protein polycystin 1, cell-cell and cell-matrix interactions § Repeated PKD domains o PKD2 gene = 4q, 10% of cases § Polycystin 2, integral membrane protein, homologous to calcium and sodium channel proteins o PKD3 gene = not yet mapped o 40% of patients have liver cysts, 10-30% have cerebral bery aneurysms, 25% have MVP · Autosomal Recessive Polycystic Kidney Disease o Kids, infants succumb rapidly to renal failure, o Liver almost always have cysts and congenital hepatic fibrosis · Medullary Sponge Kidney o Multple cystic dilations in the collecting ducts of the medulla, presenting in adults o Innocuous lesions, may predispose to calculi · Nephronopthisis-Uremic Medullary Cystic Disease Complex o Family of progressive renal disorders o Small cysts in the medulla o Four variants § Sporadic, non-familial = 20% § Familial juvenile nephrophthisis =50%, AR § Renal-Retinal dysplasia = 15%, AR § Adult-onset, 15%, AD · Acquired Cystic Disease o Dialysis related o Cortical and medullary cysts o Atypical hyperplastic epithelium ® renal cell CA · Simple Cysts o Commonly encountered, usually cortex o Smooth walls, clear serous fluid o Hemorrhage and stroma reaction ® flank pain
Glomerular Diseases · Pathogenesis of Glomerular Injury o Immune mechanisms § Anti-GBM nephritis · Abs bind noncollagenous domains of a3 chain of collagen type IV, linear pattern of staining by immunofluorescence § Heymann nephritis · Abs to megalin and receptor-associated protein, antigen on visceral epithelial cells · SUBepithelial deposits of Ag-Ab complexes = granular staining for IgG o Non-immune mechanisms § Glomerulosclerosis · Adaptive changes that occur in relatively unaffected glomeruli of diseased kidneys o Compensatory hypertrophy, hemodynamic changes like single nephron GFR, capillary and often systemic HTN § Tubulointerstitial injury · Better correlation of decline in renal fn with extent of TI damage than glomerular damage · Types of Glomerular Disease o Acute Proliferative, Posttreptococcal, Postinfections GN § Acute nephritic syndrome § Global hypercellularity § Granular IgG, IgM, C3 deposition § Subepithelial “humplike” depositions by EM ® immune complex deposition § 95% of kids recover o Rapidly Progressive (Crescetic) GN (RPGN) § Accumulation of cells in Bowman’s space § Type 1 RPGN · Anti-GBM dz, linear deposits of IgG · Goodpasture syndrome § Type 2 RPGN = immune complex –mediated · Post-infectious GN · Lumpy bumpy pattern of staining § Type 3 RPGN = pauci-immune · ANCA associated · Wegener granulomatosis · Microscopic polyarteritis nodosa · Nephrotic Syndrome o Excessive permeability of glomerular capillary wall to plasma proteins o Proteinuria > 3.5 gm/day o Vulnerability to infection o Thrombotic complications o Membranous GN § Major cause of nephrotic syndrome in adults § Diffuse thickening of the capillary wall § Diffuse granular GBM IgG staining § EM ® subepithelial deposits along GBM o Minimal Change Disease = Lipoid nephrosis § Major cause of nephrotic syndrome in kids § Uniform, diffuse effacement of foot processes of visceral epithelial cells by EM § T cells release substances increasing glomerular permeability o Focal Segmental Glomerulosclerosis § Sclerosis of some but not all glomeruli § A circulating factor is suspected as an initiator of the lesions, because this recurs after txplant § HIV patients ® collapsing variant of FSG o Membranoproliferative GN § Thickened capillary loops and proliferation of glomerular cells § Capillary has double-contour or tram track appearance § Type 1 · C3, C1q, C4, Ig’s stain in a granular manner in subendothelial deposits · SLE, Hep B/C with cryglobulinemia, schistosomiasis, a1-antitrypsin deficiency, chronic liver dz, some malignancies § Type 2 = dense deposit dz · IgG is absent as are early C’ components · C3 mephritic factor in serum, which is an Ab against C3 convertase o IgA Nephropathy (Berger dz) § One of the most common glomerular diseases § Major cause of recurrent glomerular hematuria § Mesangial proliferation and IgA deposition § Defect in immune regulation leading to increased IgA secretion § Similar IgA deposits seen in Henoch-Schonlein purpura in children § 50% develop renal failure over 20 years · Focal Proliferative Glomerulonephritis o Segments of only some glomeruli involved o Can be seen in three circumstances § Systemic disease § Component of known glomerular dz § Primary idiopathic focal GN · Chronic Glomerulonephritis o Glomeruli replaced by hyalinized connective tissue o Difficult to determine andecent lesion Glomerular Lesions Associated with Systemic Disease · SLE · Henoch-Schonlein purpura o Purpuric skin lesions, abdominal sxs, arthralgia, and GN. o Mesangial IgA deposition · Bacterial endocarditis · Diabetic glomerulosclerosis o Capillary BM thickening o Diffuse glomerulosclerosis o Nodular glomerulosclerosis = Kimmelstiel-Wilson dz · Amyloidosis · Miscellaneous
Hereditary Nephritis · Alport syndrome o GN, nerve deafness, lens dislocation, cataracts, corneal dystrophy o X-linked, mutation to a5 chain of collagen IV o Decreased a3 chain, so these patients do not recognize the Goodpasture antigen · Thin membrane disease o Familial hematuria o Genetic basis unclear
Acute Renal Failure · Acute Tubular Necrosis o From ischemia or nephrotoxins o Distal tubules and collecting ducts contain casts o Recovery = flattened tubular cells and mitoses
Pyelonephritis and Urinary Tract Infection · Pathogenesis o Bacterial colonization o Vesicoureteral reflux of organisms = congenital defects accentuated by cystitis o E. coli, Proteus, Enterobacter most frequent causes o Hematogenous seeding through septicemia (Staph and E. coli) · Acute Pyelonephritis o Patchy, suppurative inflammation, tubular necrosis, and neutrophilic casts o Advanced changes ® abscesses, necrotizing papillitis, pyonephrosis, perinephric abscesses, renal scars · Chronic Pyelonephritis and Refluex Nephropathy o Discrete, corticomedullary scars overlying dilated, blunted, deformed calyces § Obstructive · Chronic obstructive predisposes the kidney to infections, usu. caused by enteric bacteria § Reflux nephropathy · Most common cause · Begins in childhood · May present with hypertension § Xanthogranulomatous pyelomephritis · Uncommon form of CPN · Gram negative infections · Mixed inflammatory infiltrate with foamy macrophages ® large yellow, orange nodules that look like RCC on xray
Acute Drug-Induced Interstitial Nephritis · Methicillin, ampicillin, rifampicin, thiazides, NSAIDS, phenindione · Drugs act as haptens · Induce IgE and T-cell mediated immune reactions · Fever, eosinophilia, skin rash, hematuria, mild proteinuria, sterile pyuria, azotemia.
Analgesic Abuse Nephropathy · Chronic tubulointerstitial nephritis with papillary necrosis · Phenacetin-containing mixtures · Plyuria, headaches, anemia, GI sxs, pyuria, UTIs, HTN · Renal papillary necrosis · Increased incidence of transitional cell CA of renal pelvis
Other Tubulointerstitial Diseases · Urate nephropathy o Acute or chronic renal failure o Hematolymphoid malignancies who are undergoing chemotherapy · Hypercalcemia o Nephrolithiasis or nephrocalcinosis · Multiple Myeloma o Bence Jones proteinuria and cast nephropathy o Tamm-Horsfall protein = BJ proteins combine with urinary glycoproteins o Amyloidosis o Light-chain nephropathy o Hypercalcemia and hyperuricemia o Vascular disease Diseases of Blood Vessels · Benign Nephrosclerosis o Sclerosis of renal arterioles and small arteries o Thickening and hyalinization of the walls o Fibroelastic hyperplasia with medial and intimal thickening o Diffuse ischemic atrophy of nephrons ® small kidneys with granular surfaces o Blacks, those with severe HTN, people with DM do worse · Malignant Nephrosclerosis and Accelerated Hypertension o Usu. superimposed on preexisting benign essential HTN o Black men o Fibrinoid necrosis of vessel walls o Kidneys have “flea bitten” appearance o Onion-skinning of arterioles o Diastolic pressures > 130 mmHg · Renal Artery Stenosis o Unilateral ® 2-5% of cases of renal HTN o Excessive renin secretion from involved kidney o 70% - atheromatous plaque o 30% fibromuscular dysplasia o Surgery can be curative · Thrombotic Microangiopathies o Classic Childhood Hemolytic-Uremic Syndrome § After flu-like illness § Verocytotoxin-producing E. coli (shiga-like) · leukocyte adhesion · endothelin and decr. NO (both favor vasoconstriction) · Endothelial lysis o Adult HUS / Thrombotic Thrombocytopenic Purpura § Assoc. with infection, antiphospholipid syndrome, placental hemorrhage, vascular renal diseases, mitomycin and bleomycin § Fever, NEUROLOGIC SXS, hemolytic anemia, thrombi in afferent arterioles § Women < 40 yrs § Exchange transfusions, corticosteroids · Atheroembolic Renal Disease o From repair of AAAs or during intra-aortic cannulation · Renal Infarcts o 25% cardiac output o Atrial fibrillation or AMI complicated by mural thrombosis o Large infarcts of one kidney can cause HTN
Urinary Tract Obstruction · Urolithiasis o Can cause hydronephrosis o 75% calcium containing ® hypercalcemia o 15% triple (struvite) stones ® infection with urea splitting bacteria
Tumors of the Kidney · Benign Tumors o Renal papillary adenoma § Small yellow papules § Found at 7-22% of autopsies o Renal fibroma § Fibroblast-like cells and collagen o Angiomyolipoma § Seen in tuberous sclerosis § Hamartoma o Oncocytoma § Eosinophilic epithelial cells ® packed with mitochondria § From intercalated cells of collecting ducts § May be large but never metastasize · Malignant Tumors o Renal Cell CA § Von Hippel-Lindau syndrome · Gene = § Hereditary clear cell CA · Occurs without other manif. of VHL § Hereditary papillary carcinoma · AD · MET protooncogene § Major types of tumors · Clear cell = most common o Clear cytoplasm, nonpapillary o Deletion of 3p, a locus that harbors the VHL tumor-suppressor gene · Papillary CA o MET, chromosome 7 o PRCC, chrom. 1 ® large tumors in kids · Chromophobe o Prominent cell membranes with pale cytoplasm, halo around nucleus o Intercalated cells of collecting duct, good prognosis o Urothelial CA of Renal Pelvis § Present early because of obstruction § 50% of cases also have bladder tumor |
