pathology of infectious diseases I - lecture notes - julia

Question 1

what are the epithelial barriers to disease in the different regions where disease can enter (meaning what types of cells in the skin, resp tract, GI tract, genitourinary tract)?

Answer 1

epithelial surfaces

• skin - stratified squamous epithelium
• respiratory tract - ciliated columnar epithelium
• GI tract - columnar epitheilium with mucous secretion
• genitourinary tract - squamous and columnar epithelium, plus urinary epithelium - have specific receptors on them and some organisms have specialized themselves to adhere to them

Question 2

what sorts of bacteria will be in an anatomic site?

Answer 2

the normal flora, which varies based on the site potential pathogens opportunistic pathogens

Question 3

what can be the negative consequence of antibiotics on the normal flora?

Answer 3

can disturb the normal balance of bacteria by killing some of the ones we want to live

Question 4

what are opportunistic pathogens? what are some examples?

Answer 4

• largely sit in our normal flora, hardly ever cause disease, unless the host has some major defect in immune mechanisms
• they require some opportunity to become disease-causing eg pneumocystis jirovecci
• usually in peoples lungs - discovered when AIDS became common cytomegalovirus
• 70% of us have been exposed, might have had a cold or something, but if people have immunosuppression, can reactivate and cause severe and potentially lethal disease

Question 5

what are potential pathogens? what is an example?

Answer 5

organisms capable of causing disease but can also sit around on mucosal surfaces and do nothing and be part of the normal flora but can break out of that and cause disease eg. streptococcus pneumonia

Question 6

what are obligate pathogens? what is an example?

Answer 6

bacteria that, if they’re there, they always cause disease - not part of the normal flora bordetella pertussis

Question 7

how do bacteria invade?

Answer 7

usually through epithelium or into organs some can invade into individual cells

Question 8

what are virulence factors?

Answer 8

toxins that bacteria produce that make them capable of causing disease

Question 9

what are endotoxins?

Answer 9

virulence factors often in cell walls - lipopolysaccharide

Question 10

what are exotoxins?

Answer 10

virulence factors that are secreted - may mimic intra cellular signaling molecules

Question 11

what are adhesins?

Answer 11

virulence factors that allow bacteria to adhere to cell types

Question 12

what types of enzymatic virulence factors can be made?

Answer 12

• proteases
• collagenases
• phospholipases

all can disrupt cells and tissues

Question 13

how do bacteria and host cells compete for nutritional factors?

Answer 13

• major one appears to be iron
• bacteria release virulence factors that include iron binding proteins

Question 14

what is hepicidin?

Answer 14

appears to be the major protein regulating iron levels - peptide hormone that depresses the amount of iron that’s available

Question 15

what is acute suppuration?

Answer 15

production of pus - acute inflammation

Question 16

what are some forms of acute suppurative inflammation?

Answer 16

• pnemonia
• endocarditis
• pyelonephritis
• appendicitis

Question 17

what cells are involved in acute suppartive inflammation?

Answer 17

polymorponuclear leukocytes - cause production of pus

Question 18

what causes bacterial pneumonia?

Answer 18

streptococcus pneumoniae has polysaccharide capsule - main virulence factor prevents phagocytosis makes proteases that breaks down mucosal antibodies has cell wall

Question 19

what are the steps in the progression of pneumonia?

Answer 19

• normal colonizer invades bloodstream (bacteremia) or tissue (pneumonia, menigitis)
• recruitment of PMNs at the site of infection by integrin-mediated (CD18) and other processes

Question 20

what will lobar pneumonia look like? (xray, gross)

Answer 20

large white area in one lobe of lung when fixed, lobe will be light, dense, not spongy as it should be = consolidation

Question 21

what are the pathologic stages of pneumonia?

Answer 21

1: edema - leakage of fluid from vessels = serous
2: acute inflammation - recruitment of PMNs and platelets => activation of complement and coagulation cascade
3: consolidation - red and grey hepatization
4: if patient survives, get resolution that restores at least some of the normal architecture of the lung

Question 22

what is consolidation?

Answer 22

• hepatization
• lung which ought to be spongy and pink turns into something that’s not spongy and is grey and looks like liver
• can be red and grey depending on cellular comsitituents of infiltrate
• earlier stage has more RBCs and is red

Question 23

what will the edema stage of pneumonia look like histologically?

Answer 23

• serous exudate
• protein-containing fluid leaks out of vessels
• alveoli are filled with pink fluid
• if look at excudate, will be PMNs, gram positive bacteria, often in pairs

Question 24

what does the acute inflammation stage of pneumonia look like histologically?

Answer 24

• see series of other cells being recruited
• lots of cells with irregular nuclei = PMNs
• cells with more cytoplasm probably macrophages - but they’re not the predominant population
• vessels become congested - lots of RBCs in what should be really thin vessel walls
• granular pink stuff = serous fluid - was already pink - major protein in that begins to be activated by all of the parts of coagulation cascade and begins to coagulate into fiber so get pink clumps - important to allow PMNs to have something to move on

Question 25

what is the importance of the formation of fibrin in the inflammatory response?

Answer 25

PMNs can't "swim" - need structure to move one formation of fibrin provides a matrix for them to move within the site of infection

Question 26

what does the resolution stage of pneumonia look like?

Answer 26

* alveolar wall not quite normal yet * most of the inflammatory cells are macrophages cleaning up the dead cells, debris, fibrin * normal architecture of alveolar space left

Question 27

what is necrotizing pneumonia?

Answer 27

when organisms release enzymes that break down the tissue and therefore never get resolution - so never get normal architecture back, just get necrosis and scaring

Question 28

what is endocarditis?

Answer 28

infection of the heart valve

Question 29

what should the mitral valve look like? what does it look like with endocarditis? (gross)

Answer 29

thin and glistening if infected, covered in yellow stuff

Question 30

what bacteria often cause endocarditis?

Answer 30

infections from mouth acute most frequently caused by more virulent pathogens like staphylococcus aureus

Question 31

how does staphylococcus aureus cause pathogenicity?

Answer 31

* multiple virulence factors encoded by "pathogenicity island" * all can be turned on at the same time =\> very invasive and pathogenic

Question 32

how does staph aureus endocarditis start and progress?

Answer 32

* some sort of damage to heart valve that results in removal of the normal endothelial cells =\> fibrin deposited on valve =\> bacteria can now stick to it =\> massive infiltration of PMNs vegitation formed * - can destroy valve * - can make valve incapable of closing = hemodynamic deompensation * vegetations can break apart and go to lung, brain, kidneys, etc as tiny, infected emboli

Question 33

what does a normal valve look like histologically?

Answer 33

mostly collagen, underlayed by fibrous and mucsuloskeletal structure

Question 34

what does a valve with endocarditis look like?

Answer 34

* lighter pink = fibrin * darker pink = collagen of valve * dark smudges/irregular blue clumps = inflammatory cells or masses of bacteria

Question 35

what will periphearl emboli due to endocarditis look like?

Answer 35

painful nodules that you can see can also see lesions in small vessels in retina

Question 36

what does a septic infarct look like? what can cause it?

Answer 36

* clump in vessel, bacteria and inflammatory inflitrate around it * emboli from endocarditis

Question 37

what is pyelonephritis? what causes it?

Answer 37

* acute inflammation of kidney due to bacteria * frequently, these bacteria can come from members of bowel flora but more frequently associated with anatomic * often escherichia coli - member of bowel/enteric G- flora * strains that cause it seem to have specialization that allow it to adhere to the epithelium of urinary tract - allows them to ascend the ureters and get into the kidney

Question 38

what does pyelonephritis look like (grossly)?

Answer 38

red inflamed area

Question 39

what are the complications of E. coli pyelonephritis?

Answer 39

* increased risk of UTI because adheres to urinary epithelium, colonizes urethra * papillary necrosis * pyonephrosis (pus in the renal pelvis) * perinephric abscess

Question 40

what does pyelonephritis look like histologically?

Answer 40

* interstitial inflammation (in area between collecting tubules) * lots of PMNs * glomerulus won't be really involved since this doesn't come through the vascular channels * collecting tubules will be full of PMNs, then these will get out into the interstitium

Question 41

what are some possible etiologies of abdominal abscess?

Answer 41

* intestinal infection with rupture * diverticulitis * G U infections

Question 42

what types of bacteria cause abdominal abscess?

Answer 42

usually due to mixed bacterial populations

Question 43

what is the difference between peritonitis and abscess?

Answer 43

role of coagulation of serum proteins in walling off infectious process and providing framework for cellular motility

Question 44

what bacteria cause apendicitis?

Answer 44

combined infection including e. coli and baxteroides fragilis

Question 45

what are the consequences of apendicitis?

Answer 45

* full-thickness necrosis of blood vessel walls =\> serositis (peritoneal inflammation) * can also =\> abscesses

Question 46

can you treat abscesses with antibiotics? why or why not? how would you treat an abscess?

Answer 46

* no blood vessels, so can't get antibiotics to it * center also aerobic and acidic so many antibiotics don't usually work * need cell surfaces or ECM for PMN migration and phagocytosis * so treat by draining abscess and antimicrobial therapy

Question 47

what does apendicitis look like?

Answer 47

* serosal inflammation * mucosal wall being shredded, coming off

Question 48

what is an abscess?

Answer 48

when all of the pus is in one place

Question 49

what determines whether abscesses are formed in appedicitis?

Answer 49

* propensity of the two types of bacteria to form abscesses depends on virulence factors of B. fragilis * promoted by foriegn materia (vegetable fiber or barium in experimental models)