Inflammation

Definition

Inflammation is a protective physiological response initiated when the body is exposed to harmful stimuli, such as pathogens and irritants, or as a result of an autoimmune response. It may result in either a helpful or harmful process. When it is helpful to the body it is considered a healing process but when it is more harmful to the body it may be considered a disease or a disorder.

At a histological level, the process results in the stimulation of macrophages at the site of the injury, including dendritic cells, endothelial cells, and mastocytes, which release inflammatory mediators that generate a cascade of events within the body. These events may be categorized into a vascular and a cellular response, each of which ultimately serves to clear the body of invading pathogens or irritants and/or to begin the process repairing damaged tissue.

The vascular response is mediated largely by vasodilators, inflammatory mediators that cause an increase in blood flow to the injured region, leading to the characteristic redness and heat of inflammation. Vasodilators also cause increased permeability of vascular walls, allowing plasma to move into the surrounding tissue. This mechanism leads to swelling and serves to dilute the pathogen or irritant that triggered the response. There are also a variety of plasma-derived cascade systems that use different sets of mediators to develop and propagate the inflammatory response. These include the complement system, which increases removal of pathogens, the kinin system, which propagates vasodilation, the coagulation system, which initiates clotting at the site of injury, and the fibrinolysis system, which counterbalances clotting.

The cellular component of the inflammatory response occurs as a direct result of the vascular response and results in an increased concentration of leukocytes at the site of injury. Leukocytes, immune cells that include phagocytes, granulocytes, monocytes, and lymphocytes, are designed to destroy invading pathogens, making them invaluable components of the inflammatory response. Normally leukocytes are not provided much opportunity to move from blood vessels into tissue, as the flow of blood moves them swiftly through the blood vessels. Following the vascular response, however, the concentration of cells in the blood increases and the speed of blood flow decreases, allowing leukocytes to extravasate into surrounding tissue at an increased rate. Once in the tissue the process of chemotaxis gradually directs them toward the site of injury where they may finally go to work destroying pathogens.

Finally, inflammation may be classified as either acute or chronic. Acute inflammation is characterized by immediate onset in response to injury or the presence of pathogens and persists only as long as that injury or pathogen persists. In contrast, chronic inflammation is a delayed response to persistent foreign bodies, non-degradable pathogens, or an autoimmune response and can last for months or years.

Inflammation may be diagnosed by a variety of methods depending on the symptoms described by the patient. For instance, inflammation due to a puncture wound may only require a physical examination while abdominal pain caused by an inflamed appendix or an autoimmune disease would likely require a more in-depth battery of tests and imaging techniques.

Acute inflammation is typically treated with short-acting anti-inflammatory agents, such as ________, and antibiotics to prevent infection. Treatment of chronic inflammation is more complicated, often requiring longer-lasting anti-inflammatory drugs, such as steroids and _______. Finally, inflammation caused by autoimmune disease requires a more comprehensive treatment plan designed to reduce inflammation and prevent tissue damage over the course of a patient’s life.

Celsus 200 years ago – rubor calor dolor tumor laesio function (Virchow (1821 -1902

Hyperemia calor

Radiation Hepatitis – Hyperemia

The straight line and the hyperemia are characteristis features radiation induced change22975 Courtesy Ashley Davidoff MD

Principles

Acute Inflammation

Hallmarks – Celsius

Tumor

Rubor

Calor

Dolor

Laesio Functio

Acute Cholecystitis

This is a high power photomicrograph of mucosa and muscular layer of a gallbladder with acute cholecystitis. Just a bit of the lumen is shown, indicated by the empty slit at one side of the picture. The fronds are flat, and a single layer of epithelium can be seen (at the edge of the slit). The epithelium is interrupted by acute inflammatory exudate which is extruding from the mucosa into the lumen. Hemorrhage is present beneath the epithelium, and there is acute inflammation through the wall.11926.8s  gallbladder cholecyctitis pathology histopathology Courtesy Barbara Banner MD

Hemorrhagic Congestion in the Gallbladder Wall

00151 gallbladder wall inflammation acute cholecystitis histopathology

Bile Inciting Inflammation

This photomicrograph shows a small piece of bile, in its yellow natural color, surrounded by foreign body type giant cells, surrounded in turn by a sea of WBCs and foamy histiocytes. The latter contain bile and lipid salts. The bile and the foamy histiocytes account for the yellow color seen grossly in xanthogranulomatous cholecystitis. The “granulomas” are true foreign body-type granulomas composed of phagocytes trying to break down chunks of bile which have worked their way into the gallbladder wall during inflammatory disruption of the mucosa. 11938.8  gallbladder dx cholelithiasis histopathology Courtesy Barbara Banner MD

Acute Calculous Cholecystitis

This is a photograph of a resected gallbladder opened longitudinally. The gallbladder is being held open by hemostats, as the inflammatory process made the wall thicker and stiffer than normal. Note that the cut face of the wall between the hemostats is about 3 – 4 mm thick. The dark red color is imparted by hemorrhage in the wall. The multiple gallstones are probably causing some degree of obstruction.11927.8s  gallbladder cholecytitis grosspathology Courtesy Barbara Banner MD

Cystic Arterioles in the Submucosa – Hyperemia

82006c04.8s liver gallbladder blood supply hepatic artery cystic artery cystic arterioles submucosa wall edema hyperemic mucosa red = hepatic artery green = lumen of the gallbladder CTscan Courtesy Ashley Davidoff MD Copyright 2008

Cystic Arterioles and Venules in the Submucosa

82006c05.8s liver gallbladder blood supply hepatic artery cystic artery cystic arterioles submucosa wall edema hyperemic mucosa red = hepatic artery green = lumen of the gallbladder CTscan Courtesy Ashley Davidoff MD Copyright 2008

Arteries, Veins and Lymphatics in the Gallbladder Fossa

00140 gallbladder wall gallbladder fossa normal artery duct liver interface histopathology

Swelling

Transudation and Exudation Causing Swelling

71695c02 colon splenic flexure fx fat induration dirty fat Gerotas fascia lateral conal fascia thickened thickening of the interstitium acute inflammation inflammatory exudate diverticulitis large bowel CTscan Davidoff MD 71695c01

Swelling Supraorbital Region and Maxillary Sinus

48717b01 skin bone swelling acute traumatic injury inflammation fracture inferior orbital wall roof of maxillary sinus trauma 3D volume rendering CTscan Davidoff MD

Hyperemia

Acute Calculous Cholecystitis wit Gallbladder Wall Edema and Hyperemia

72365c01 gallbladder wall fluid in gallbladder fossa positive sonographic Murphy’s sign inflammation mechanical obstruction infection hyperemia hypervascularity dx acute calculous cholecystiis Davidoff MD

Acute Cholecystitis with Transmural Induration

16203c01.8s gallbladder edematous wall hyperemic wall distended gall bladder edema in the wall fluid in the fat surrounding the gallbladder indurated fat acute cholecystitis stones visible on CT scan CTscan Courtesy Ashley Davidoff MD copyright 2008

Acute Cholecystitis

16141c01s.8 gallbladder stones cholelithiasis hyperemic wall edematous wall small filling defects in dependant position in the infundibulum distended gall bladder edema in the wall fluid in the gallbladder fossa gbf normal bile duct MRI T1 weighted image with gadolinium and fat saturation T2 weighted MRCP normal pancreatic duct Courtesy Ashley Davidoff MD copyright 2008

The Normal (left) and Abnormal (right) Red and Swollen GE junction – Reflux Esophagitis

01239b01.800 esophagus stomach GE junction gastroesophageaal junction inflammed inflammation GERD red swollen reflux esophagitis grosspathology Courtesy Ashley Davidoff MD

Chemical Peptic Esophagitis

73405 esophagus redness patches inflammation chemical acute esophagitis endoscopy Courtesy Joshua Namias

Before and After Acute Pncreatitis

Swelling of the Pancreas from Edema and Leakage of Pancreatic Fluid

70369c01 pancreas time acute pancreatitis before after enlarged fluid interstitial fluid inflammation kidney obstruction CTscan Davidoff MD 70369c02

Acute Pancreatitis

This patient presented with acute abdominal pain following an alcoholic binge. The pancreas shown in pink in image b, looks relatively normal, but is surrounded by a exudate (red ) which is characteristic of this entity. The exudate has extended around the colon (white surrounded by red ring on the left side)

. 40396c02 Courtesy Ashley Davidoff MD code abdomen colon colon cutoff sign code pancreas pancreatic tail fx induration exudate code anterior pararenal space left colic gutter Gerota’s fascia lateral conal ligament fx thickened lcode liver hypodensity dx steatosis fatty liver code dx acute alcoholic pancreatitis with fatty change in the liver and colonic narrowing imaging radiology plain film CTscan acute inflammation mechanical

Chemical Inflammation

Before and After Acute Pncreatitis

Swelling of the Pancreas from Edema and Leakage of Pancreatic Fluid

70369c01 pancreas time acute pancreatitis before after enlarged fluid interstitial fluid inflammation kidney obstruction CTscan Davidoff MD 70369c02

Reflux Esophagitis

12253.800 esophagus cellular infiltrate inflammation stratified columnar epithelium reflux esophagitis histopathology Courtesy Barbara Banner MD

Left Maxillary Sinusitis Complicated by Brain Abscess – MRI

71604.c03 40 year old female with headache brain maxillary sinus frontal lobe fx air fluid level parafalcine falx cerebri a= T1 weighted b= T2 weighted c = T2 weighted d= FLAIR dx acute on chronic left maxillary sinusitis with brain abscess air fluid level thickened mucosa of maxillary sinus MRI Davidoff MD 71604.c02 71604.c03 71604.c04 71604.c02b

CNS

Sarcoidosis Involving the Basal Meninges

40406c Courtesy Ashley Davidoff MD code lung fx interstium fx thickening dx interstitial lung disease ILD code pancreas abdomen lymph nodes fx calcified code brain meninges fx calcifications code dx sarcoidosis imaging radiology CT scan code inflammation immune

CVS

Sarcoidosis of the Heart

49740c01 34 male with sarcoidosis presents with dizzineess and complete heart block cardiac heart LV sarcoidosis complete heart blosk early gadolinium delayed gadolinium enhancement of the LV wall left ventricle inflammation MRI T1 Davidoff MD

Calcific Myocarditis

This is a CT of the chest at the level of the heart filmed on narrow windows showing a dense ventricular septum. The autopsy specimen showed calcific myocarditis. Courtesy Ashley Davidoff MD 24672 code heart septum dense calcific calcified calcification myocarditis inflammation cardiac imaging radiology CTscan

Takayasu’s Aortitis

16917b aorta fx irregular fx narrow dx Takayasu arteritis imaging radiology MRI Courtesy Ashley Davidoff MD DB

Takayasu’s Arterirtis

The series of images are from the angiogram of a 14 year old female who presented with seizures and an elevated blood pressure. Images a and b show multiple stenoses within the carotids best seen at the level of the bifurcation into external and internal arteries. In addition in b, the aortic arch shows non critical narrowing just after the origin of the left common carotid vessel. Note that the right subclavian artery is not seen and presumably is accluded at its origin. The abdominal angiogram shows a significant narrowing of the left renal artery with post stenotic dilitation, and stenotic disease in the infrarenal abdominal aorta. The multicentric nature of the disease in a young female is athognomonic of Takayasu’s arteritis. 35155c Courtesy of Laura Feldman MD. code CVS artery aorta arteritis inflammation Takayasu’s carotid thorax arch renal abdomen pulseless

Kawasaki Arteritis and Coronary Artery Aneurysm

07587 heart cardiac aneursym coronary artery Kawasaki’s areteritis grosspathology Courtesy Ashley Davidoff MD

Takayasu’s Arterirtis

Polyarteritis Nodosa

Occlusive Vascular Disease: Causes of Vascular Occlusion – Polyarteritis Nodosa. This is a medium power photomicrograph from a bowel in a patient with Polyarteritis Nodosa. Bowel is commonly affected in this disorder. The medium sized artery seen here has undergone a deeply eosinophilic (fibrinoid) change. Notice that there is a surrounding inflammatory infiltrate of WBCs and formation of aneurysmal dilatation. This can result in massive hemorrhage if the aneurysm ruptures. colon large bowel artery small bowel fx aneurysm inflammation dx polyarteritis nodosa histopathology Courtesy Barbara Banner MD 12889

Henoch Schonlein Arteritis Segmental Spasm with Hemorrhage

Young female presents with GI bleed hemorrhage bleeding blood small bowel colon SMA superior mesenteric artery jejunal branches ileocolic artery fx arterial spasm fx contrast extravasation RLQ in cecum dx arteritis angiitis vasculitis arteriopathy dx Henoch -Schonlein arteritis angiography angiogram Courtesy Ashley Davidoff MD 28514 28515 28516 28517 surgical specimen showed plaque like ulcers in the bowel consistent with chronic ischemia

Acute

Acute Pneumonitis Secondary to Chemotherapy – Drug Reaction

47095 lung chest fx lobar infiltrates fx air bronchogram dx chemotherapy related pneumonitis acute inflammation CTscan Davidoff MD

Bronchovascular Inflammation

47170c01.800 bronchocentric inflammation lung bronchovascular bundle chest inflammation peribronchial halo air trapping mosaic perfusion ground glass changes alveolar change air bronchogram acute bronchovascular inflammation ddx allergic collagen vascular disease infection CTscan

Scleroderma

This coronally reformatted CT of the posterior aspect of the chest shows interstitial lung disease within the lower lobes in this patient with scleroderma. The upper lobes were relatively spared. Courtesy Ashley Davidoff MD. 30476 code lung pulmonary interstitium interstial disease thickening lower lobes chronic inflammation fibrosis scleroderma collagen vascular disease imaging radiology CTscan

Necrotizing Granuloma

72372c03 60 female with long history of smoking lung nodule slow growth SUV 1.3 right lower lobe dx necrotizing granuloma Most necrotizing granulomas are related to infection. Wegener’s granulomatosis Churg-Strauss syndrome – vasculitis sarcoidosis usually non necrotizing CTscan PETscan Davidoff MD

Subacute Inflammation

Chronic Inflammation

Environmental Causes of Chronic Inflammation

Asbestosis

47060c01 chest lung fx shaggy heart border reticular changes interstitial lung disease interstitium honeycombing pleural calcification fibrosis dx asbestosis CTscan Davidoff MD

End Stage Fibrosis – IPF

47145c01 lung interstitium interstitial disease parenchymal destruction shaggy heart border fx honeycombing interstitial pulmonary fibrosis IPF CTscan Davidoff MD

GIT

Normal GE Junction and Ulcerating Esophagitis

02464b Normal Davidoff MD01239 Ashley Davidoff MD code esophagus ulcer ulcerating inflammed inflammation red congested esophagitis grosspathology

Normal and Quinidine Ulcer

39562b01 esophagus single contrast barium wallow normal anatomy Davidoff MDCourtesy Ashley Davidoff MD 01258 esophagus + quinidine ulcer barium swallow inflammation upper GI UGI imaging radiology contrast X-Ray

Radiation Induced Esophagitis – Fixed Narrowing

This series of esphageal images from a double contrast barium swallow shows a long segment stenosis in mid esophagus assocated with punctate accumulations of contrast. The patient is known to have lung carcinoma and hasirradiation and the findings are consistent with radiation esophagitis. Courtesy Ashley Davidoff MD 38394c code GI esophagus radiation esophagitis ulceration

13 mm stricture in Esophagus

49430c01 esopagus GE junction stricture hiatis hernia barium swsllow upper GI size Davidoff MD

Stricture of the Esophagus

73406.800 esophagus narrowing stenosis stricture distal esophageal stricture peptic stricture endoscopy Courtesy Joshua Namias

Normal Antrum and Stomach with Hemorrhagic Gastritis

01978b stomach gastric pylorus duodenum junction normal anatomy12263 code stomach gastric + hemorrhagic gastritis grosspathology

Hemorrhagic Gastritis

12264 code stomach gastric + hemorrhagic gastritis grosspathology

Linear Erosions of Antral Gastritis

49746b01 normal01323 01323b01 code stomach + linear erosions erosive gastritis + upper GI UGI imaging radiology contrast X-Ray inflammation

Normal Antrum, Pylorus and Duodenum

01978b stomach gastric pylorus duodenum junction normal anatomy

Normal Bulb and Crohn’s Duodenitis

33637b02 normal

01954 duodenum fx thickened folds dx duodenitis Crohn’s disease upper GI UGI imaging radiology contrast X-Ray Courtesy Ashley Davidoff MD DB

Normal and Denuded Ulcerating Mucosa with Cobblestone of the Terminal Ileum in Crohn’s Disease

12231 colon large bowel cecum ileocecal valve appendix fx normal anatomy Courtesy Barbara Banner MD02477b02 small bowel terminal ileum mucosa fx inflammation ulceration fx nodules fx cobble stone thick walled dx Crohn’s disease ileocecal valve grosspathology Courtesy Dr Gutkin MD DB

Normal and Cobblestone

32525b01 small bowel terminal ileum colon ileocecal valve large bowel normal anatomy UGI SBFT Courtesy Ashley Davidoff MD

43159 small bowel fx ileum fx nodular mucosa fx cobblestone fx thickened folds fx narrowed lumen dx Crohns UGI SBFT Courtesy Ashley Davidoff MD AFD AFD

Cobblestone of the Terminal Ileum

43159 small bowel fx ileum fx nodular mucosa fx cobblestone fx thickened folds fx narrowed lumen dx Crohns UGI SBFT Courtesy Ashley Davidoff MD AFD AFD

02477b02 small bowel terminal ileum mucosa fx inflammation ulceration fx nodules fx cobble stone thick walled dx Crohn’s disease ileocecal valve grosspathology Courtesy Dr Gutkin MD DB

Terminal Normal terminal Ileum and Ileum Chronic Inflammation with Secondary Narrowing

Gross photomicrograph of a terminal ileum from a patient with Crohn’s disease. Notice the stricture which tapers to a maximum at the ileocecal valve. Notice also the irregular linear longitudinal ulcers with tufts of remaining mucosa between them. Notice the sharp segmental cutoff to more normal-appearing ileum as you move away from the ileocecal valve. Notice that the bowel wall in the involved area is thickened. code small bowel ileum fx thickening fx linear ulcers dx Crohns disease Crohn’s disease grosspathology Courtesy Barbara Banner MD12231 colon large bowel cecum ileocecal valve appendix fx normal anatomy Courtesy Barbara Banner MD 12287 l

Ileum Chronic Inflammation with Secondary Narrowing and USscan of the Terminal ileum

12287 l

Stenoses in Bile Ducts Caused by Sclerosing Cholangitis

24209.800 76 male with jaundice liver bile duct fx narrowed fx multicentric narrowing Dx sclerosing cholangitis chronic inflammation pancreas pancreatic duct ampulla fx normal MRI T2 weighted Davidoff MD

Cholecysto-duodenal Fistula

26909c04.8s gallbladder air stomach duodenum thickened dx penetrating ulcer dx cholecystoduodenal fistula IVC inferior vena cava filteer small prominent folds valvulae conniventes ascites CTscan C+ Courtesy Ashley Davidoff MD copyright 2008

Before and After Acute Pncreatitis

Swelling of the Pancreas from Edema and Leakage of Pancreatic Fluid

70369c01 pancreas time acute pancreatitis before after enlarged fluid interstitial fluid inflammation kidney obstruction CTscan Davidoff MD 70369c02

Hemorrhagic Pancreatitis

16851b04 Courtesy Ashley Davidoff MD code pancreas + fx mass hemorrhage acute pancreatitis acute hemorrhagic pancreatitis imaging radiology CTscan inflammation

Skin

Laceration

82875.800 trauma hand knuckle carpal bones skin abrasion blood coagulation redness inflammation vein Davidoff MD Davidoff photography

Types

Hemorrhagic Inflammation

Hemorrhagic Pancreatitis

16851b04 Courtesy Ashley Davidoff MD code pancreas + fx mass hemorrhage acute pancreatitis acute hemorrhagic pancreatitis imaging radiology CTscan inflammation

Complex Pleural Effusion Thickened Pleura Chronic Inflammation Dystrophic Calcification

74243b01 74242 74242b01 88 year old male complex effusions pleura pleural space thickened pleura thickening unilateral atelecactasis pleural calcification calcified CTscan Courtey Ashley DAvidoff MD

Metaplasia – Sign of Chronic Inflammation

This medium power photomicrograph shows gallbladder mucosa with an inflammatory infiltrate of mononuclear cells. The lumen is the clear area, and a tiny part of muscular layer can be seen at the opposite side of the picture. Look carefully and you will find one area near the lumen with goblet cells, like intestinal epithelium. This is intestinal metaplasia. Deeper in the mucosa near the muscular layer is a cluster of a few glands which do not have a tall columnar epithelium. They resemble gastric glands, and in fact this is gastric metaplasia. Metaplastic epithelium occurs frequently throughout the biliary and gastrointestinal tracts in chronic inflammatory conditions. In the gallbladder it has no significance other than being part of the changes due to chronic inflammation.11932.8s gallbladder chronic cholecystitis histopathology Courtesy Barbara Banner MD

Chronic

Porcelain Gallbladder – Variant of Chronic Inflammation

This is a specimen xray of a resected gallbladder. The walls were thin, fibrotic and heavily calcified, accounting for the radiodense (white) areas on the radiograph. This variant of chronic cholecystitis is a risk factor for development of carcinoma.11939.8s gallbladder porcelain gallbladder X-ray Courtesy Barbara Banner MD

Porcelain Gallbladder – Variant of Chronic Inflammation

This photomicrograph at low power shows most of the full thickness of the wall of a gallbladder. The lumen is the clear area at one side of the picture. The pale homogeneous area down the middle is fibrous replacement of the wall. The little nubbin of tissue and cholesterol clefts along the lumen represents what is left of the mucosa. The darker, zig-zag structure at the side opposite the lumen represents where the gallbladder wall is calcified. This calcification and fibrosis of the entire gallbladder wall is the diagnostic feature of porcelain gallbladder.11940.8s gallbladder porcelain gallbladder histopathology Courtesy Barbara Banner MD