LECTURE 7 ACUTE INFLAMMATION DEF. RESPONSE OF VASCULARIZED TISSUE TO ENDO- OR EXOGENIC FACTORS

CELSUS; TUMOR, DOLOR, CALOR, RUBOR VIRCHOFF: FUNCTIO LAESA

1. DAMAGE 2. TRANSUDATE 3. PROLIFERATION INFLAMMATION

• Inflammation - a response triggered by damage to living cells/tissues. The inflammatory response is a defense mechanism that evolved in higher organisms to protect them from e.g. infection and injury. VASCULAR RESPONSE DISTURBANCES OF MICROCIRCULATION IN INFLAMMATORY FOCUS CELLULAR RESPONSE TO INFLAMMATION CELLULAR RESPONSE TO INFLAMMATION

MACROPHAGES – ACTIVATION AND ACTION ROLE OF MACROPHAGES

CHEMICAL MEDIATORS OF INFLAMMATION (NO) NITRIC OXIDE IN INFLAMMATION

• Nitric oxide (NO) is a signaling molecule that plays a key role in the pathogenesis of inflammation. • It gives an anti-inflammatory effect under normal physiological conditions. On the other hand, NO is considered as a pro-inflammatory mediator that induces inflammation due to over production in abnormal situations. NITRIC OXIDE IN INFLAMMATION • NO is believed to induce vasodilatation in cardiovascular system and furthermore, it involves in immune responses by - activated macrophages, which release NO in high concentrations. • In addition, NO is a potent neurotransmitter at the neuron synapses and contributes to the regulation of apoptosis. NO is involved in the pathogenesis of inflammatory disorders of the joint, gut and lungs. Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells. Five VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene. These isoforms differ in their molecular mass and in biological properties such as their ability to bind to cell-surface heparan-sulfate proteoglycans. The expression of VEGF is potentiated in response to hypoxia, by activated oncogenes, and by a variety of . VEGF induces endothelial cell proliferation, promotes cell migration, and inhibits apoptosis. In vivo VEGF induces angiogenesis as well as permeabilization of blood vessels, and plays a central role in the regulation of vasculogenesis. STAGES OF ANGIOGENESIS

ROLE OF VEGF AND bFGF Deregulated VEGF expression contributes to the development of solid tumors by promoting tumor angiogenesis and to the etiology of several additional diseases that are characterized by abnormal angiogenesis CLASSIFICATION OF

ALTERATIVE INFLAMMATION EXUDATIVE INFLAMMATION PROLIFERATIVE INFLAMMATION ACUTE INFLAMMATION (sometimes as FULMINATING) SUBACUTE, SUBCHRONIC INFLAMMATION CHRONIC INFLAMMATION CHRONIC EXACERBATING (EXACERBATION) INFLAMMATION

TERMINOLOGY OF INFLAMMATIONS: TO LATIN OR GREEK NAME OF THE ORGAN ADD THE ENDING - ITIS

DIABETES, type 1 – autoimmune mechanism ALTERATIVE INFLAMMATION A GROUP OF INFLAMMATIONS WITH DOMINATION OF INJURY OF TISSUE; CAUSE OF NECROSIS IT RARELY OCCURS IN THE ,,CLEAN”, PURE FORM

ACUTE ANTERIOR POLIOMYELITIS – EPIDEMIC HEPATITIS HEINE-MEDINA DISEASE HEINE-MEDINA DISEASE/POLIO • Polio, or called poliomyelitis or infantile paralysis, is an infectious disease caused by the poliovirus • In around 1 percent of infections, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying motor neurons within the spinal cord, brain stem, or motor cortex. This leads to the development of paralytic poliomyelitis, the various forms of which (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS affected. ACUTE ANTERIOR POLIOMYELITIS – HEINE-MEDINA DISEASE EXUDATIVE INFLAMMATION SEROUS INFLAMMATION

1. 2. 3.

1. TRANSUDATE 2. (SEROUS) 3. EXUDATE (HEMORRHAGIC)

SEROUS PLEURITIS EXUDATIVE INFLAMMATION CATARRHAL INFLAMMATION

CATARRHAL BRONCHITIS ASTHMA ASTHMA • Defined by the National Asthma Education and Prevention Program as a "chronic inflammatory disorder of the airways" in which many cells and cellular elements play a role - in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells • In susceptible individuals, causes episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early morning • Episodes are usually associated with widespread but variable airflow obstruction that is often reversible, either spontaneously or with treatment • Inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli • Very common, affects 14 - 15 million Americans -causes 3,000 US deaths annually status asthmaticus

The cut section of the hyperinflated lung of a patient dying in status asthmaticus appears essentially normal.

Status asthmaticus: unremitting attacks due to exposure to previously sensitized antigen; may be fatal, usually in patients with a long history of asthma EXUDATIVE INFLAMMATION CATARRHAL INFLAMMATION

INFLAMMATORY POLYPS OF NOSE HYPERTROPHY OF EPITHELIUM IN CHRONIC NOSE DURING CATARRHAL COLITIS A CHRONIC CATARRHAL INFLAMMATION

The acute inflammatory response in pericarditis can produce either serous or purulent fluid or a dense fibrinous material Neoplastic, tuberculous, and purulent pericarditis may be associated with large effusions that are hemorrhagic and exudative Prolonged pericarditis may result in persistent accumulation of pericardial fluid which may form a thick coating that surrounds the myocardium causing constrictive pericarditis SUPERFICIAL FIBRINOUS INFLAMMATION

FIBRINOUS COR VILLOSUM – PERICARDITIS FIBRINOUS HAIRY HEART PERICARDITIS (MICROSCOPY)

EXUDATIVE INFLAMMATION SUPERFICIAL FIBRINOUS INFLAMMATION

INFECTIOUS MONONUCLEOSIS FIBRINOUS PERITONITIS INFECTIOUS MONONUCLEOSIS • Infectious mononucleosis is a clinical entity characterized by sore throat, cervical lymph node enlargement, fatigue and most often seen in adolescents and young adults and lasting several weeks. • It can be caused by a number of pathogens, but often due to primary Epstein-Barr virus (EBV) infection. EBV is a γ-herpesvirus that infects at least 90% of the population worldwide. EXUDATIVE INFLAMMATION PROFOUND FIBRINOUS INFLAMMATION

UREMIC ENTEROCOLITIS PSEUDOMEMBRANOUS LARYNGOTRACHEITIS UREMIA • Uremia is a clinical syndrome associated with fluid, electrolyte, and hormone imbalances and metabolic abnormalities, which develop in parallel with deterioration of renal function. The term uremia means urine in the blood. • Uremia more commonly develops with chronic kidney disease (CKD), especially the later stages of CKD, but it also may occur with acute kidney injury (AKI) if loss of renal function is rapid. Urea itself has both direct and indirect toxic effects on a range of tissues. UREMIC ENTEROCOLITIS

• colitis characterized by hemorrhages in the mucosa, occurring in renal failure, possibly owing to the irritant effect of ammonia formed by breakdown of increased urea in the intestinal secretions. EXUDATIVE INFLAMMATION PROFOUND FIBRINOUS INFLAMMATION

FIBRINOUS PNEUMONIA PROFOUND FIBRINOUS COLITIS DIPHTHERIA • Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Signs and symptoms may vary from mild to severe. • They usually start two to five days after exposure. Symptoms often come on fairly gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat. • Complications may include myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets. In 2015, it resulted in 2,100 deaths EXUDATIVE INFLAMMATION PROFOUND FIBRINOUS INFLAMMATION: DIPHTHERITIC INFLAMMATION (ESCHAROTIC)

DIPHTHERITIC ANGINA GASTRITIS

CHRONIC HYPERTROPHIC GASTRITIS

CHRONIC ATROPHIC GASTRITIS

CHRONIC ATROPHIC GASTRITIS WITH INTESTINAL METAPLASIA SYDNEY CLASSIFICATION

• Inflammation • Activity • Atrophy • Intestinal Metaplasia • Dysplasia • Helicobacter pylori ULCERATIVE COLITIS

• Affects 4 - 12 per 100,000 in U.S., usually whites, peak onset ages 20 - 25 and 70 - 80 years; no gender preference • Almost always rectal involvement at disease onset but may develop rectal sparing and patchiness after treatment or chronic disease, resembling Crohn's colitis ULCERATIVE COLITIS • Symptoms: relapsing, bloody mucoid diarrhea (stringy mucus) with pain / cramps relieved by defecation; lasts days / months, then remission for months / years; initial attack may cause medical emergency for fluid and electrolyte imbalance • Complications: perforation, toxic megacolon (due to toxic damage to muscularis propria and neural plexus with shutdown of neuromuscular function), iliac vein thrombosis, carcinoma, lymphoma This gross appearance is characteristic for ulcerative colitis. The most intense inflammation begins at the lower right in the sigmoid colon and extends upward and around to the ascending colon. At the lower left is the ileocecal valve with a portion of terminal ileum that is not involved. Inflammation with ulcerative colitis tends to be continuous along the mucosal surface and tends to begin in the rectum. ULCERATIVE COLITIS Flattened mucosa with numerous pseudopolyps ULCERATIVE COLITIS (EROSIONS) ULCERATIVE COLITIS (CRYPTS ABSCESS ) EXUDATIVE INFLAMMATION (ORGANIZATION)

PERITONEAL ADHESIONS

CARNIFICATION OF LUNG AFTER PNEUMONIA FIBRINOUS EXUDATE

ORGANIZATION OF FIBRINOUS EXUDATE IN EPICARDIUM.

YOUNG GRANULOMATOUS TISSUE WITH A LARGE AMOUNT OF BLOOD CELLS WITH COLLAGEN FIBRES (RED) THANK YOU Thank you !