9/21 Flashcards
Morphological Types of Acute Inflammation
Neutrophils appear first then macrophages come, neutrophils have nuclei with multiple lobes
- Serous Fluids: clear fluid with few/no cells, transudate, erythematous vesicles or blisters
- Fibrinous: bread and butter pericarditis, Cell poor and protein rich
- Purulent: cloudy exudate, cell/protein rich
Has cell debris, fibrin, bacteria, neutrophils
Staphylococcus bacteria like pneumonia and the clap
Bronchopneumonia has exudate (fibrin and neutrophils) in alveoli, leptomeningitis
- Pseudomembranous: colitis from C. difficile, fibrino-purulent yellow/gray exudate mushrooms on colon/pharanyx, neutrophil/macrophages and fibrin on top of epithelial cells
- Ulcers: epithelial surface that is excavated by shedding of inflamed necrotic tissue, can be due to acute/chronic inflammation
Common in skin, GIT, bladder, can also be on cornea
Leptomeningitis
Fever, headache, vomit, stiff neck, photophobia, confusion
Purulent exudate in the subarachnoid space, see neutrophils and macrophages
Lumbar puncture shows increased protein content and neutrophils (exudate)
E. Colinfor infants, Strep. pneumoniae for infant/elderly, N. meninglitidis for teens/young adults
Pulmonary Abscess
Liquefactive necrosis rich in cell debris, fluid, macrophages, neutrophils
Nice round red nodule surrounded by blue
Necrosis is walled off by a fibrin wall, forms circle
Caused by Staph, Strep, and fungi
Infiltrative Inflammation (Non-Granulomatous)
Dominated by humoral adaptive immune response
- Macrophages: very light purple, pale chromatin and red nucleolous
- Lymphocytes: mainly dark purple, scant cytoplasm and dark round nuclei with prominent nucleoli
- Plasma Cells: light purple cytoplasm and dark purple nucleus, clock-face nuclear chromatin, amphophilic cytoplasm
- Eosinophils: bunch of bright pink cytoplasm dots and dark purple nucleus
Viral/bacterial Pneumonia Histology
Viral: Edema in the alveoli, light pink spaces instead of white, few mononuclear cells
Death of epithelial cells lining the alveoli results in cell poor exudate that coagulates into dark pink hyaline membrane
Bacteria: fibrin and neutrophils fill alveoli, more purple cell things filling alveoli than viral
Granuloma Histology
Macrophages form outer ring around epithelioid cells, lymphocytes near macrophages as well, fibroblast cells on the outside
Large pink oval surrounded by sea of purple dots
Granulomatous Inflammation
Noncaseating: foreign body, fungus, parasite, immune
Caseating: M. tuberculosis, Bartonella henselae
Necrotizing: fungus, immune
Different Types of Granulomas
Caseating: from bacteria, Langerhans type giant cells have pearl necklace of nuclei, foreign body giant nuclei if all bunched up in middle
Sarcoidosis: non-caseating granuloma Inflammation that lacks a known etiologic agent
Necrotizing Granuloma: coin lesion in chest, from fungal infections, light purple circle surrounds pinkish purple circle in middle
Granulomas from Fungus: use methenamine silver to identify yeast
Parasitic Schistosomiasis: form non-caseating granuloma, ova in tissue
Acute Phase Response
Collection of endocrine, metabolic, or neurological changes that are shortly observed after infection, microbial products, and inflammation
Characterized by fever, increased/decreased synthesis of plasma proteins by liver, behavioral changes, and increase in leukocytes
IL-1, IL-6, TNFalpha, and IFN activate immune cells and also act on liver to produce certain acute phase proteins
IL-6 is main cytokine mediator of acute phase response
Hypothalamus starts endocrine to make glucocorticoids that increase liver response to IL-6
Acute Phase Response Proteins
C-reactive protein
Serum amyloid protein
Mannose-binding lectin
Alpha-2 macroglobulin
Proteins that reduce iron availability: hepatoglobulin, ferritin, hepcidin, ceruplasmin
Alpha1 anti-trypsin/chymotrypsin
Coagulation proteins
Complement proteins
C-Reactive Protein
Produced in liver, no specific marker of inflammation
Binds to bacteria/fungi cell wall, also to PCs on dead/damaged human cells
Activates classical/alternative pathways of the complement system
Bind to Fc receptors and act as opsonin, activates macrophages to produce cytokines
Serum Amyloid A
Made in liver, associates with HDL
Binds to TLR to activate cells, chemotactic to neutrophils/mast cells
Stimulate cytokine synthesis, involved in pathogenesis of amyloid A-type amyloidosis and chronic inflammation
Random Acute Phase Response Proteins
- Alpha-2-Macroglobulin: inhibits proteases involved in coagulation and fibrinolysis
Iron limiting proteins- prevent bacteria from getting iron since needed for growth
- Haptoglobin: binds Hemoglobin
- Ferritin: binds iron
- Hepcidin: prevents iron release from ferritin in macrophages and intestines
- Ceruloplasmin: oxidizes iron
6/7. Alpha 1 Anti-trypsin/chymotrypsin: downregulate inflammation
- Coagulation Proteins: prothrombin, von Wilbrand Factor, fibrinogen, plasminogen
- Complement Proteins
Erythrocyte Sediment Rate
Increased fibrinogen levels during acute Phase Response causes RBCs to adopt Rouleaux formation and stack
ESR above 20 mm/hr denotes inflammation, is no specific indicator of inflammation though like C-reactive protein levels
Normal vs. Fever
Body temp. is controlled by hypothalamus
Diurnal variation: low 6 AM, high 4-6 PM
Fever: increase in body temp. That exceeds diurnal variation and occurs in conjunction with increase in hypothalamic set point, pyrogens reset the set point
Hyperpyrexia: temp. above 40 °C, severe infections and CNS hemorrhage
Hyperthermia (heat stroke): no intrinsic body pyrogens or altered set point
Mechanism of Fever
Infection/Inflammation activates NF-kappaB in leukocytes/endothelial cells, makes secrete pyrogenic cytokines (IL-1beta, IL-6, TNF-alpha, IFN) into circulation
Pyrogenic cytokines induce PGE2 synthesis, binds to EP3 receptors on neurons and causes glial cells to release cAMP to activate neuronal endings from the thermoregulatory center of the hypothalamus
Thermostatic set point raised, heat conservation and fever ensue
Phases of Fever
Initiation Phase: elevation of set point brings chills, shivering, rigor
Plateau Phase: core body temperature equals set point and minimal chills, shivering, and rigors
Defervescence: core body temperature is above set point, patients feel warm and are sweating, recovery phase
Impact of a Fever
Positive:
Increase IFN-gamma production
Stimulate antibody synthesis
Stimulate leukocyte motility and phagocytosis
Inhibit bacterial growth by limit Fe, Cu, Zn
Increase cell death in virally infected cells
Negative:
Heart rate increases but decreased cardiac output
Decreased blood flow to brain, seizures and CNS damage
Acidosis from higher respiratory rate, oxygen consumption, and metabolic rate
Behavioral Responses to Fever
Mediated by IL-1, IL-6, TNF-alpha, IFN-gamma
Malaise
Pain (PGE2)
Sleepiness (PGD2)
Anorexia (PGE2)
White Blood Cell Count
Normal WBC level: 5-10k/uL
Leukocytosis: increase in WBCs (15-25k/uL)
Leukemoid Reaction: markedly increased leukocyte count (40-100k+), resembles leukemia
Neutrophilia: increase in neutrophils, from bacterial infections
Eosinophilia: seen in asthma, hay fever, parasites
Lymphocytosis: viral infections, chronic inflammatory states
Leukopenia: decreased WBCs from certain infections/diseases like viruses, Rickettsia, Protozoa, TB, and cancers
Left Shift: bacterial infection/acute inflammation increase neutrophils, bands appear in blood and are precursor cells to the mature neutrophils
Bone marrow sends bands into blood stream that mature to neutrophils there, also called bandemia
Leukocyte Adhesion Deficiency
Recessive disease, defects in leukocyte Adhesion to endothelial cells, presented in kids
Delayed umbilical cord detachment, omphalitis
Severe recurrent bacterial infections to skin/mucosal surfaces, no pus formation, gingivitis and periodontitis common
Neutrophilia from labs, neutrophils can’t transmigrate
Treatment: antibiotics and bone marrow transplant if severe LAD 1
LAD I: structural defects in neutrophil integrins, mutation in CD18
LAD II: absence of selectin on surface, Golgi GDP-fucose transporter defect
LAD III: defect in integrin activation process
Chronic Granulomatous Disease
Mutations in genes for NADPH oxidase, phagocytes can’t make hydrogen peroxide or superoxide to kill microbes via oxidative burst
Genetically heterogenous with 70% X-linked recessive and 30% autosomal recessive, rare
Infections-
Common sites: lung, skin, lymph nodes, liver
Normal response to viral infections
Staph aureus are common bacterial infections, Aspergillus (fungi) commonly infect but make only a little sick so hard to diagnose
Diagnosis-
Tissue biopsy: look for granulomata
Oxidative burst test (Flow cytometry), Nitroblue tetrazolium test is old method, confirm via genetic testing
Treatment: antibiotics/antifungal prophylaxis, INF-gamma or bone marrow transplant
