Pathology Lectures 5 And 6

Front 1

how long does it take for a PMN to develop?

Back 1

about two weeks

Front 2

six morphological stages that PMNs pass through during development?

Back 2

1) myeloblast
2) Promyeloblast
3) myelocyte
4) metamyelocyte
5) non-segmented (band) neutrophils
6) segmented neutrophils (mature cells)

Front 3

When are neutrophil granules generated and what is there use?

Back 3

-Generated during cell differentiation and produced for storage

Front 4

Three main types that the content of neutrophil granules can be divided into?

Back 4

Primary (azurophil) granules
Secondary (specific) granules
tertiary (small storage) granules

Front 5

Primary (azurophil) granules

Back 5

contain:
-myeloperoxidases
-defensins
-elastase
-phospholipase A2
-etc.

Front 6

Secondary (specific) granules

Back 6

contains:
-lysozyme
-lactoferrin
-collagenase
-phospholipase A2
-Etc

Front 7

Tertiary (small storage) granules

Back 7

contain:
-gelatinase
-cathepsins
-glucutonidase
-mannosidase
-etc

Front 8

Monoctyes

Back 8

possess migratory, chemotactic, and phagocytic activities as well as PRRs and receptors for opsonins such as IgG Fc domains, CRP and C3b

Front 9

Macrophages

Back 9

-possess migratory, chemotactic and phagocytic activities to a greater extent than those of the monocyte
-possess similar receptors

Front 10

normal macrophages

Back 10

-histocytes of CT
-kupffer cells of liver
-Alveolar macrophages
-Pleural and peritoneal macrophages

Front 11

M1 inflammatory macrophages

Back 11

-aggressively destroy miccroorganisms and tumor cells
-release proinflammatory cytokines
-process and present antigens

Front 12

M2 inflammatory macrophages

Back 12

-remove dead and dying cells
-promote angiogenisis
-promote tissue remodeling
-may be involved in tumor cell survival

Front 13

Mast cells of CT

Back 13

granules contain heparin

Front 14

mast cells associated with mucosal surfaces of the respiratory systems

Back 14

smaller and contain chondroitin sulfate

Front 15

Immune mediated degranulations of mast cells?

Back 15

-type 1 hypersensitivity
-IgE (cytophilic for mast cells and basophils) binds by Fc domain
-Antigen binding results in cross linking of IgE molecules and triggers degranulation

Front 16

nonimmune mechanisms of degranularion of mast cells?

Back 16

-Physical injury (heat trauma)
-fragmens of the complement system (C3a and C5a)
-Toll receptors binding PAMPS (TLR-2, TLR-4, etc)
-Leukocyte derived histamine releasing proteins
-neutropeptides (subtance P, etc)
-Cytokines (IL-1, IL-8 etc)

Front 17

What other inflammatory mediators do mast cells produce other than those produced by degranulation?

Back 17

-prostaglandins and leukotrienes
-cytokines, esp TNF
-platelet activating factor

Front 18

How are basophils different than mast cells?

Back 18

-they are normally found in circulation rather than in the tissue
-they arise from bone marrow progenitor cells and follow different maturation pathways.
-synthesize significant amounts of interleukin IL-4

Front 19

function of basophils?

Back 19

-allergic reactions (anaphylaxis)
-defense against parasites
-major source of IL-4 (development of Th2 type immunity-humoral immunity)

Front 20

Eosinophils are characteristic of what type of reactions?

Back 20

IgE mediated reactions:
-hypersensitivity
-allergic
-asthma responses

Front 21

Which WBC is the primary defense against fungi, protazoa and parasitic worms (pathogens too large to consume by endocytosis)?

Back 21

Eosinophils

Front 22

ECF

Back 22

-Eosinophilic chemotactic factor
-released by activated mast cells and basophils
-attracts eosinophils to sites of allergic inflammation

Front 23

What do eosinophils produce

Back 23

-prostaglandins
-leukotrienes
-cytokines (IL-1, IL-6, IL-8 and TNF), -granules that contain hydrolytic enzymes
-MBL (major basic protein) and cationic protein which are toxic to parasites

Front 24

MBL

Back 24

-major basic protein
-toxic to parasites
-also toxic to other cells and is thought to play a role in airway damage in asthma

Front 25

Main functions of eosinophils

Back 25

-IgE mediated reactions
-cytotoxic to tumors
-modulates allergic inflammation (release enzymes that break down histamine and some leukotriens)
-antigen presenting cells
-primary defense against large pathogens

Front 26

Which category of lymphocytes to Natural killer (NK) cells belong to? Why?

Back 26

-Null cells (non T and non B)
-lack surface T and B receptors
-are fully functional as soon as they are formed (innate immunity)

Front 27

What are NK receptors called?

Back 27

-killer inhibitory receptors (KIRs)

Front 28

What do killer inhibitory receptors (KIRs) do?

Back 28

-binds to class I MHC
-binding = inhibition on killing so normal cells are spared but infected/stressed cells have reduced class I MHC molecules so they are killed by NK cells

Front 29

What surface molecules would promote killing by NK cells?

Back 29

MICA and MICB (MHC I Class related sequence A and B)

Front 30

What is the mechanism of a NK cell when killing another cell?

Back 30

-release perforins and granzymes which make pores in cells
-enzymes enter cell and activate apoptosis

Front 31

Activated NK cells are major sources of what?

Back 31

-cytokins such as IFNy and TNF

Front 32

What does ADCC stand for and what does NK cell participation in ADCC result in?

Back 32

-ADCC = antibiody dependent cell cytotoxicity
-results in killing of cells, including bacterial cells, bound with surface antibiods

Front 33

What do Platelets look like? where do they arise from?

Back 33

-anucleate disc shaped cell fragments
-arise from megakaryocytes in the bone marrow

Front 34

Were do platelets arise from?

Back 34

megakaryoctyes in the bone marrow

Front 35

function of platelets?

Back 35

-mainly homeostasis
-formation of homeostatic plug
-initiation and regulation of clot formation
-inflammatory mediators, including vasoactive substances

Front 36

Dense or delta granules

Back 36

(platelets)
-histamine
-serotonin
-calcium
-ADP

Front 37

Alpha granules

Back 37

(platelets)
-fribrinogen and various other clotting factors
-platelet derived growth factor (PDGF) promotes fibroblast proliferation and activity in repair
-Transforming growth factor beta (TGF-B) promotes epitherlial and fibroblast development

Front 38

lamba granules

Back 38

(platelets)
-typical lysosomes contaiing various hydrolytic enzymes

Front 39

How do platelets function in inflammation?

Back 39

-platelet adherence
-aggregation and degranulation following contact with vascular injury or thrombin
-degranulation happens after release of serotonin and histamine

Front 40

Margination

Back 40

-brings leukocytes into contact with endothelial cells
-BP drops with vasodilation and increased permeability
-blood flow slows (esp in postcapillary venules)
-leukocytes move to peripheral region (plasma zone)

Front 41

Tethering

Back 41

rolling motion of leukocytes as they move along the endothelial surface

Front 42

Mechanisms of tethering?

Back 42

-selectins interact with endothelial cells and leukocyte surface membrane mucin like glycoproteins

Front 43

What mediators will cause tethering/ expression of selectins in blood vessels?

Back 43

-inflammatory mediators (histamine, IL-1, TNF as well as thrombin
-(integrins are other attachment molecules that are also activated by inflammatory mediators)

Front 44

___ and ___ selectins on endothelial cells reversibly bind leukocyte glycoproteins

Back 44

E and P selectins

Front 45

binding

Back 45

firm attachment of leukocytes to the endothelium

Front 46

Tethering

Back 46

rolling motion of leukocytes as they move along the endothelial surface

Front 47

Mechanisms of tethering?

Back 47

-selectins interact with endothelial cells and leukocyte surface membrane mucin like glycoproteins

Front 48

What mediators will cause tethering/ expression of selectins in blood vessels?

Back 48

-inflammatory mediators (histamine, IL-1, TNF as well as thrombin
-(integrins are other attachment molecules that are also activated by inflammatory mediators)

Front 49

___ and ___ selectins on endothelial cells reversibly bind leukocyte glycoproteins

Back 49

E and P selectins

Front 50

binding

Back 50

firm attachment of leukocytes to the endothelium

Front 51

intravascular activation by leukocytes when bound to PAMPs?

Back 51

involves chemotactic factors (esp. IL-8), that result in the full expression of leukocyte cell surface integrins

Front 52

extravascular activation by leukocytes when bound to PAMPs?

Back 52

at site of injury, PMNs are stimulated and undergo:
-Degranulation and release of lysosomal contents
-generation of the oxidative burst
-production of eicosanoids
-productions of cytokines

Front 53

unenhanced attachment for endocytosis?

Back 53

-surface membrane proteins recognize PAMPS common in microbial walls but not humans. (peptidoglycan, techoic acids, lipopolysaccharide, mannans, & glucans)
-
-

Front 54

enhanced attachment for endocytosis?

Back 54

-opsonization
-opsonins (C3b, CRP, and antibodies IgG and IgM) attach to and coat microbial surfaces
-Phagocytic cells have surface receptors for these molecules

Front 55

Internalization in endocytosis?

Back 55

-attachment initiates internalization in which pseudopods form and enclose the particle or fluid
-membrane fluid forms a vacuole

Front 56

Oxygen dependent mechanisms in killing during endocytosis

Back 56

respiratory or oxidative burst of activity characterized by a sudden increase in oxygen consumption with the production of toxic reactive oxygen metabolites.

Front 57

toxic reactive oxygen metabolites produced during O2 dependent killing

Back 57

-superoxide (O2-)
-Hydrogen peroxide (H2O2)
-Hypochlorous acid (HOCl)
-Hydroxyl radical (OH)

Front 58

5 oxygen independent mechanisms in killing during endocytosis

Back 58

-lysosomal hydrolytic enzymes
-Bactericidal / permeability increasing protein
-Defensins
-Lactoferrin
-Lysozyme

Front 59

Bactericidal/permeablity increasing protein?

Back 59

-cationic proteins that is bactericidal for many gram-neg bacteria.
-non toxic to gram-pos bacteria or eukaryotic cells

Front 60

Defensins

Back 60

-cationic proteins contained in Primary granules of PMNs and the lysomes of macrophages
-can kill a wide variety of bacteria, fungi, and some viruses

Front 61

5 examples of leukocyte defects

Back 61

-Chronic granulomatous disease
-Chediak - Higashi disease
-Leukocyte adhesion deficiency
-Lazy leukocyte syndrome
-Myeloperoxidase deficiency

Front 62

Chronic granulomatous disease

Back 62

-Microbal killing defect
-lack of NADPH oxidase (needed to produce hydrogen peroxide and the superoxide radical)
-autosomal recessive and X linked forms

Front 63

Chediak - Hiashi disease

Back 63

-dysfunction of the microtubules resulting in poor chemotaxis and failure of the lysocomes to fuse with phagosomes
-Autosomal recessive inheritance

Front 64

Leukocyte adhesion disease

Back 64

-Adhesion molecule deficiencies (there are several forms) that infterfere with cell adhesion prior to emigration
-autosomal recessive inheritance

Front 65

Lazy leukocyte syndrome

Back 65

-cytoskeletal defects that interfere with cell movement including chemotaxis.
-unknown inheritance

Front 66

Myeloperoxidase deficiency

Back 66

-Defect in microbial killing due to the lack of production in HOCL
-least serious

Front 67

reactive lymphadenitis

Back 67

-enlarge lymph nodes
-caused by delivery of antigen presenting cells by lymph circulation

Front 68

lymphangitis

Back 68

-inflammation involving lymphatic vessels

Front 69

Lympbadenitis

Back 69

-inflammation involving lymphatic nodes

Front 70

4 possible outcomes of inflammation

Back 70

-resolution
-regeneration
-non functional repair
-chronic inflammation

Front 71

examples of tissues with non-functional repair

Back 71

fibrosis, gliosis, scarring, cicatrix formation, cicatrization

Front 72

Phase 1 of metabolism

Back 72

-hydrolysis
-oxidation and reduction

Front 73

phase 2 of metabolism

Back 73

(water soluble compounds are readily excreted)
-Methylation
-Sulfation
-Glucuronidation
-Conjugation

Front 74

Mechanisms of toxicity

Back 74

exposure --> absorption at portals of entry --> toxic metabolites --> distribution to body --> interaction with proteins, DNA, RNA, receptors --> **TQ** toxic effects (genetic, carcinogenic, reproductivity and immunotoxicity)

Front 75

**pollutants in air

Back 75

chemical vapors, organic or chemical dusts, heavy metals, tobacco smoke and microorganisms.

Front 76

**6 pollutants that the EPA sets upper limits for

Back 76

-sulfur dioxide
-carbon monoxide
-ozone
-nitrogen dioxide
-lead and particulate matter
(smog)

Front 77

**how is ozone formed?

Back 77

nitrogen oxides of automobile exhaust

Front 78

**smog?

Back 78

Ozone + particulate matter

Front 79

**How does smog effect ppl?

Back 79

Production of free radicals from ozone--> toxicity --> injure epithelial cells of respiratory tract and type 1 alveolar cells. Highly detrimental to pts with asthma

Front 80

indoor air pollutants?

Back 80

CO, nitrogen dioxide, tabacco smoke, asbestos, wood smoke, radon.

Front 81

whats in wood smoke?

Back 81

various oxides and carbon particles containing carcinogenic hydrocarbons

Front 82

**radon

Back 82

-radioactive gas widely present in soil and in homes

Front 83

**Bioaerosols

Back 83

microbiologic agents (causing infections) and allergens e.g. pet dander, dust mites, fungi, molds (**sick building syndrome)

Front 84

Effects of indoor air pollution?

Back 84

-Chronic brochitis and asthma
-pneumoconioses
-Cancer-cigarette smoking exposure to asbestos, radioactive dusts

Front 85

**Anthracosis

Back 85

accumulation of carbon dust in lungs --> emphysema especially in the smoker

Front 86

**silicosis

Back 86

silica dust-sand blasters, glass workers, miners and metal grinders, cement workers

Front 87

**chronic exposure in silicosis?

Back 87

-Pulmonary Fibrosis with solicotic nodules. Silica is a potent lung irritant and stimulates fibrosis
-gradual reduction in lung capacity --> dyspnea.
-increased risk of TB

Front 88

**Caplan syndrome

Back 88

-silicosis + rheumatoid arthritis
-acute exposure to large quantities of silica
-exudative pneumonitis with respiratory failure and death within 1-2 yrs

Front 89

Coal workers pneumoconiosis?

Back 89

-accumulation of coal dust in lungs
-fibroblast stimulation and inflammatory response to macrophage injury
-Silicosis and TB may occure
-severe stage = -progressive massive fibrosis (PMF)--> prgressive dyspnea

Front 90

**black lung disease

Back 90

-coal workers pneumoconiosis morphologic
-fibrosis with black nodules
-emphysema with obliterative vasculitis

Front 91

**complications of Coal workers pneumoconiosis/black lung disease?

Back 91

-pulmonary hypertension (PHT) --> RV hypertrophy with **Cor Pulonale (hard lung)

Front 92

Asbestosis

Back 92

Chronic exposure to asbestos fibers.

Front 93

persons at risk for asbestosis?

Back 93

-shipyard, roofing, brake lining and insulation workers
-ppl exposed to older buildings --> **school children

Front 94

**Interstitial pneumonitis

Back 94

-asbestosis
-chronic diffuse interstitial fibrosis of lungs

Front 95

morphological features of Asbestosis?

Back 95

-Interstitial pneumonitis
-thickened pleura with pleural plaques, some calcifies
-beaded asbestos bodies with clubbed ends in macrophages

Front 96

**Complications of Asbestosis?

Back 96

-Bronciectasis, **cor pulmonale and cancer
-**mesotheliomas occure in 10% of heavily exposed persons, all die within one year
-Bronchial carcinomma 5 times more likely to occur
-increased incidence of cancer of stomach, colon, kidneys and lymphomas

Front 97

** other diseases caused by smoking?

Back 97

-chronic bronchitis, emphysema, PUD, osteoporosis, thyroid diseases (graves disease, ocular disease (macular degeneration and cataracts)

Front 98

Effects of alcohol: Liver

Back 98

fatty liver with heptamegaly, cirrhosis leading on to hepatic cancer

Front 99

Effects of alcohol: pancreas

Back 99

Acute and chronic pancreatitits leading on to pancreatic insufficiency and stones

Front 100

Effects of alcohol: heart

Back 100

Alcoholic Cardiomyopathy, a form of dilated cardiomyopathy (beer-drinkers heart). Alcoholics are more susceptinle to arrthymias and sudden death

Front 101

Effects of alcohol: Skeletal muscle

Back 101

-muscle weakness leading on to debilitating chronic myopathy.
-Acute alchoholic rhabdomyolosis can be fatal.

Front 102

Effects of alcohol: endocrine system

Back 102

feminization of male alcoholics: loss of libido, gynecomastia and female estucheon develops. Impaired estrogen metabolism, low levels of testosterone and **testicular atrophy are also seen.

Front 103

Effects of alcohol: GI tract

Back 103

Direct toxic effect on mucosa of esophagus and stomach (chronic gastritis); also causes hypersecretion of gastric HCL. Reflux esophagitis and peptic ulcers more common

Front 104

**Mallory-Weiss Syndrome

Back 104

tears at esophago-gastric junction, may cause severe hemorrhage.

Front 105

Effects of alcohol: blood

Back 105

-Megaloblastic anemia
-due to folate and B12 deficiency and hypersplenism may cause hemolytic anemia

Front 106

Effects of alcohol: immune system

Back 106

Alcoholics are prone to many infections, may be due to immuno-supression.

Front 107

Effects of alcohol: bone

Back 107

-increase risk of osteoporosis in alcoholics esp. postmenopausal women.
-increase incidence of aseptic necrosis of head of femur in male alcoholics

Front 108

Effects of alcohol: Nervous system

Back 108

-general cortical atrophy
-nutritional deficiency

Front 109

**Wernicke Encephalopathy

Back 109

-mental confusion, ataxia,polyneuropathy (B1 deficency), disturbed cognition, ophthalmoplegia

Front 110

**Korsakoff syndrome

Back 110

retrograde amnesia and confabulatory symptoms

Front 111

**central pontine Myelinolysis

Back 111

-Progressive weakness of bulbar muscles--> respiratory paralysis.
-caused by electrolyt imbalance, usually after electrolyte therapy

Front 112

Drug abuse

Back 112

-Marijuana, cocaine and heroin can cause sudden death: pulmonary edema, respiratory failure and cardiac arrest
-IV use --> bacterial infections of skin, viral infections (e.g. hepatitis, AIDS), endocarditis and brain abscess

Front 113

**Heavy metals

Back 113

Arsenic mercury and lead

Front 114

**Mercury

Back 114

acute poisoning - contaminated fish, grain --> renal acute tubular necrosis, cerebral edema. Ch. poisoning - from fungicides, dermatologic ointments

Front 115

**Lead

Back 115

exposure from paint spraying, batteries, highway work,
-lead paints = chief source of toxicity in children

Front 116

**Effects of lead poisoning?

Back 116

-neurotoxicity, peripheral neuritis (foot wrist drop), lethargy, ataxia, encephalopathy. **Gingival "lead line", Renal proximal tubular acidosis (Fanconi syndrome), abdominal pain (lead colic), Anemia, Basophilic stippling of RBCs

Front 117

**Adverse reaction to therapeutic or diagnostic agents (idosyncrasy and hypersensitivity)

Back 117

-skin eruptions
-hepatic fatty change
-cholestasis
-hepatitis
-massice liver cell necrosis
-interstitial nephritis,
-renal papillary necrosis
-liver failure

Front 118

**asprin overdose

Back 118

vomiting, hypokalemia, acidosis, bleeding, coma

Front 119

**Reye syndrome

Back 119

asprin in usual doses in children with viral illness, causing rashes, jaundice, severe anaphylaxis, coma

Front 120

**High radiosensitivity

Back 120

-bone marrow
-lymphoid system
-hair follicles
-germ cells
-epithelium (e.g. GI)
-lung

Front 121

**Active radiation sickness

Back 121

(High radiosensitivity )
-hair loss
-nausea, vomiting dirrhea
-infection
-bleeding tendency
-anemia

Front 122

**Moderate radiosensitivity

Back 122

body tissues such as:
-connective tissues
-blood vessels
-breast
-bladder
-brain

Front 123

**Low radiosensitivity

Back 123

organs such as:
-kidney
-liver
-pancreas
and tissues such as:
-muscle, bone and nerve
-When these organs are within therapeutic radiation field, only gradual loss of function results

Front 124

Tumor cell types: High radiosensitivity

Back 124

-germ cell tumors
-lymphomas
-leukemia

Front 125

**Tumor cell types: Moderate radiosensitivity

Back 125

-Carcinoma skin
-cervix
-breast
-lung
-esophagus
-pancreas
-bladder
-neuroblastoma

Front 126

**Tumor cell types: Low radiosensitivity

Back 126

-gliomas
-sarcomas
-melanoma
-renal cell carcinomas

Front 127

Lactoferrin

Back 127

-An iron binding protein found in the secondary granules of PMNs
-Its iron sequestering activity deprives certain iron requiring bacteria, thus interfering with their growth

Front 128

Where are Lysozymes found?

Back 128

-found in many tissues + primary and secondarys graunules of PMNS, & lysosomes of monocytes and macrophages

Front 129

How do lysozymes work?

Back 129

-degrade peptidoglycans of the gram-positive bacterial cell walls. (Gram-neg bacteria are resistant to its action)

Front 130

During endocytosis, how does digestion work?

Back 130

Primary lysosomes containing hydrolytic enzymes fuse with the phagosome to form the phagolysosome (secondary lysosome) in which digestion takes place

Front 131

Nuetrophil extracellular traps (NETs)

Back 131

-web like structures released by PMNs that can trap microorganisms
-comprised of web fibers composed of chromatin and serine proteases that trap, isolate and kill microbes extracellularly

Front 132

4 ways PMNs can damage host cells and tissues

Back 132

-Cell death
-frustrated phagocytosis
-regurgitation
-autoimmune diseases

Front 133

How does cell death damage host cell tissues?

Back 133

-if not by apoptosis can release hydrolytic enzymes, toxic oxygen metabolites and other potentially damaging substances into adjacent tissues

Front 134

How does frustrated phagocytosis damage host cell tissues?

Back 134

-if targets cannot be ingested then degranulation and release of damaging substances occurs

Front 135

How does regurgitation damage host cell tissues?

Back 135

-leakage of damaging substances during phagocytosis

Front 136

**polyneuropathy

Back 136

direct toxic effect and vitamin deficiecies. Numbness, pain weakness and ataxia

Front 137

**Arsenic

Back 137

chronic toxicity due to exposure in fruit sprays, weed killers, industrial compounds.
-Cause skin pigmentation, malaise, paralysis.
-increased incidence of liver and lung cancer

Front 138

acteaminophen

Back 138

hepatic necrosis and liver failure (esp in large doses)

Front 139

Phenacetin

Back 139

analgesic nephropathy --> renal papillary necrosis

Front 140

steroid hormones

Back 140

estrogens: prolonged use --> endometrial Ca

Front 141

DES (diethylstilbestrol)

Back 141

use by mother during pregnancy --> carcinoma of vagina in daughters

Front 142

oral contraceptives

Back 142

gallstones, MI, cerebral thrombosis, DVT, pulmonary embolism.