Pathology Objectives

Front 1

Define disease

Back 1

Disease = absence of health, deviation from normal, dyshomeostasis, imbalance

Front 2

Factors that influence occurrence of disease:
Host (7)
External (6)

Back 2

Host Factors: heredity, age, sex, immunity, nutrition, mental status, species
External Factors: management, climate, microorganisms, chemicals, physical factors, nutrition

Front 3

Disease outcomes (3)

Back 3

return to health
ongoing disease
death

Front 4

Levels of study (7)

Back 4

Levels of study:
population – epidemiology
Animal – clinical signs
Organs and tissues – gross path
Cellular – histopath
Chemical – clin path
Molecular – molecular path, DNA
Etiological – cause: genetic, infectious, chemical, nutritional,

Front 5

Define pathogenesis

Back 5

pathogenesis = process of initiation and development of disease

Front 6

Define diagnosis (2)

Back 6

diagnosis=
process to understand a disease

final conclusion made about the disease

Front 7

Cytosol

Back 7

cytosol = fluid component of cytoplasm that surrounds cell contents

place of most intermediary metabolism

free ribosomes produce proteins

Front 8

Mitochondria

Back 8

energy production –oxidative phosphorylation

derived from intracellular prokaryote: Rickettsia prowazekii

Front 9

Endoplasmic reticulum

Back 9

membrane bound space continuous with outer nuclear membrane

produces proteins, lipids, and carbohydrates: incorporated into organelles or secreted; sequester into vesicles, bud, fuse

rough: ribosomes that produce proteins, most glycosylated before leaving ER (proteins formed in cytosol are not glycosylated)

smooth: lipid synthesis, detoxification of lipid soluble toxins into water soluble nontoxic substances (biotransformation); abundant in hepatocytes for lipoprotein prod and detox and in muscle for sequestering Ca from cytosol (sarcoplasmic reticulum)

Front 10

Golgi apparatus

Back 10

stacks of membrane-bound sacs near nucleus

modifies, packages, sorts, exports products from ER – control center

Front 11

Lysosomes
primary and secondary

Back 11

membrane bound sacs of enzymes that degrade

primary lysosomes newly formed by budding off golgi
secondary lysosomes - from fusion of primary lysosomes with vesicles, morphologically more variable than primary, content more heterogeneous with hydrolases and substrates

Front 12

Peroxisomes

Back 12

small vesicles with enzymes that conduct oxidative reactions

bud off smooth ER

catalase – converts H2O2 into water

detoxification and breakdown of fatty acids

major site of O2 utilization but don’t produce energy – remnants of organelle that O2 metabolism before mitochondria developed?

Front 13

Cytoskeleton

Back 13

shape, org, movement

microfilaments - thin actin and thick myosin

microtubules - tubilin

intermediate filaments

Ca conc regulates assembly/disassembly

Front 14

Nucleus

Back 14

location of cellular DNA

nuclear envelope – double membrane of 2 lipid bilayers; outer is continuous with ER; inner has nuclear pores

histones – DNA-binding, regulate folding
1% of mammalian genome is involved in coding for essential proteins

Gene is piece of chromosome

Genome is DNA from all chromosomes

Site of DNA replication and RNA synthesis

Nucleolus – aggregate of DNA

Front 15

Ectoderm derivatives

Back 15

CNS and PNS
epidermis

Front 16

Mesoderm derivatives

Back 16

mesenchyme: connective tissue, fibroblasts, osteoblasts
Muscle
Kidney (part of it)
Heart and blood

Front 17

Cell Cycle
G1

Back 17

G1 phase = growing and priming itself for division

Front 18

Cell Cycle
S

Back 18

S phase = DNA synthesis (doubles DNA content, 2 identical sets of chromosomes)

Front 19

Cell Cycle
G2

Back 19

G2 phase = gap between DNA synthesis and cell division

Front 20

Cell Cycle
M

Back 20

M phase = cell division

mitosis is nuclear division
cytokinesis is cytoplasmic division

2 genetically identical cells

Front 21

Cell Cycle
G0

Back 21

G0 phase = resting; exited cell cycle and not directing metabolism towards replication

Front 22

Cell Cycle - complex regulation
Movement between phases controlled by concentrations of ___________________ in cell – proteins that are synthesized at specific times during cycle; mediated thru complexes with ____________-dependent _______________

Back 22

Movement between phases controlled by concentrations of CYCLINS in cell – proteins that are synthesized at specific times during cycle; mediated thru complexes with CYCLIN-dependent KINASES

Front 23

Labile cells

Back 23

Labile cells = always in cell cycle; intestinal epithelium (8hr), bone marrow, epidermis

Front 24

Stable cells

Back 24

Stable cells = remain in G0 until stimulated; hepatocytes, fibroblasts

Front 25

Permanent cells

Back 25

Permanent cells = highly differentiated and do not divide, do not enter into cell cycle; neurons, cardiac myocytes (?)

Front 26

Mechanisms for cell aging (3)

Back 26

alterations in gene expression – cumulative change

telomere shortening – short DNA sequences at ends of chromosomes maintained by telomerase, telomerase is not in somatic cells

progressive metabolic injury – oxidative processes damage membranes; lipofuscin is wear and tear pigment

Front 27

Morphology of aging cells (4)

Back 27

irregular nuclei
vacuolated mitochondria
lipofuscin accumulation
abnormal metabolic products

Front 28

Apoptosis
def and sig

Back 28

apoptosis = physiological cell death; programmed

damage to the cell makes it a liability, remove damaged cells

maintains homeostatic balance

Front 29

Major components of ECM (3)

Back 29

structural: collagen and elastin

absorptive: glycosaminoglycans and proteoglycans

adhesive: fibronectin and laminin

Front 30

Cell's major responses to injury (3)

Back 30

adaptation
sublethal damage (injured)
death

Front 31

Major causes of cell injury (4)

Back 31

changes in stimulation or demands – hormone stimulation, functional demands

changes in nutrients available – too few (O2), too many (glucose)

genetic alterations

injury – reversible (metaplasia) or irreversible non-lethal injury, lethal injury (necrosis)

Front 32

Define hyperplasia

Back 32

increase in number of cells

Front 33

define physiologic hyperplasia
example

Back 33

physiologic hyperplasia = replicate to fulfill functional responsibilities; transient stimuli; cell numbers return to normal

endometrium during pregnancy
mammary while lactating
fibroblast during healing

Front 34

define pathologic hyperplasia
example

Back 34

pathologic hyperplasia = replicate in response to persistent, excessive, or inappropriate stimuli; detrimental; response often normal but result contributes to damage; stimuli and hyperplasia long-term and persistent; enlarged tissue or organ

parathyroid hyperplasia secondary to renal disease
goiter

Front 35

define hypertrophy

Back 35

hypertrophy = increase in size of a cell; sometimes with hyperplasia, stimuli the same

Front 36

define physiologic hypertrophy
example

Back 36

physiologic hypertrophy = enlarge to fulfill functional responsibilities; transient stimuli; return to normal size

uterine smooth muscle during pregnancy
mammary during lactation

Front 37

define pathologic hypertrophy
example

Back 37

pathologic hypertrophy = enlarge due to persistent, excessive, or inappropriate stimuli; cell response contributes to disease instead of maintaining homeostasis; long-term and persistent; enlarged organ or tissue

cardiac myocyte in failing heart contribute to abnormal flow

Front 38

define atrophy

Back 38

atrophy = decrease in size of cell, also decrease in number of cells; cell is smaller

Front 39

define physiologic atrophy
example

Back 39

physiologic atrophy = shrink b/c decreased stimulation or decreased demand; termination of physiologic event and atrophy returns cell/tissue to its normal resting state

aging

endometrium after parturition
myocytes when stop training

Front 40

define pathologic atrophy
example

Back 40

pathologic atrophy = shrink b/c inappropriate loss of stimuli or detrimental events; long-term or permanent; shrunken tissue/organ; small cells with otherwise normal appearance

muscle after denervation due to trauma

Front 41

define metaplasia

most common

Back 41

metaplasia = replacement of one mature cell type with another; local stem cells change pattern of differentiation; occurs in tissue; response to irritation/injury

columnar/cuboidal to squamous epithelium

Front 42

3 major mechanisms of cell injury

Back 42

loss of membrane integrity
loss of ability to produce energy
genetic damage

Front 43

3 major pathways to loss of membrane integrity

Back 43

free-radical induced injury
phospolipase-induced injury
direct membrane damage

Front 44

Protective mech against free radicals

Back 44

vit E, A, C
iron and copper binding proteins
superoxide dismutase
catalase

Front 45

phospholipase activation (losing membrane integrity)

Back 45

decreased energy -->
membrane pumps can't maintain gradients -->
cytoplasmic Ca increases -->
phospholipase activated

Front 46

Major changes in cells depleted of energy

Back 46

failure of energy-dependent pumps
cell swelling
decreased intracellular pH
decreased protein synthesis
degradation of cytoskeleton
membrane degradation
leakage organelle contents
organelle dysfunction

Front 47

3 major morphologic features of sublethal cell injury

Back 47

cell swelling
fatty change
intracellular accumulations

Front 48

define mutation

Back 48

mutation = permanent change in DNA from damage that is not repaired

Front 49

4 categories of genes that are commonly affected in cells that undergo neoplastic transformation
(genes involved in major life events)

Back 49

genes that:
promote cell growth
inhibit cell growth
regulate apoptosis
regulate DNA repair

Front 50

define pleomorphism

Back 50

variable cell size and shape

feature of neoplastic cells

Front 51

2 pathways of cell death

Back 51

apoptosis
necrosis

Front 52

Apoptosis requires _____
apoptosis does not have _____

Back 52

apoptosis requires energy
apoptosis does not have tissue damage/inflammation

Front 53

final pathway of apoptosis mediated by ________-ases

Back 53

final pathway of apoptosis mediated by caspases

Front 54

end point of apoptosis

Back 54

membrane-bound vesicles/apoptotic bodies that are removed by phagocytosis

Front 55

morphologic features of necrosis

Back 55

disruption of membranes
degeneration of nucleus
mitochondrial swelling
"ground glass" smooth homogenous cytoplasm
vacuolation

=tissue damage

Front 56

postmortem autolysis

Back 56

postmortem = all cells are affected and all at same stage, no evidence of host response/inflammation

Front 57

antemortem autolysis (necrosis)

Back 57

antemortem (necrosis) = groups of affected and non-affected cells, various stages, evidence of host response

Front 58

basic patterns of disease (6)

Back 58

developmental
metabolic
vascular
inflammation
immunologic
neoplasia

Front 59

coagulative necrosis

Back 59

coagulative necrosis = cell death due to hypoxia and inability to maintain energy (apoptosis if energy is available); basic outline of cell/tissue retained, not normal but can still recognize, ghost-like

Front 60

liquefactive necrosis

Back 60

liquefactive necrosis = infiltration of lots of leukocytes; occurs with infectious agents like bacteria that attract leukocytes; normal tissue replaced with liquefactive debris due to proteolytic activity of leukocyte and dying cells enzymes

pus = area of liquefactive necrosis

Front 61

caseous necrosis

Back 61

caseous necrosis = chronic inflammation; infectious agents that cause chronic granulomatous inflammation

a form of coagulative necrosis where necrotic cells have fragmented into amorphous debris mass

original tissue structure gone

Front 62

gangrenous necrosis

Back 62

gangrenous necrosis = ischemia

coagulative necrosis with subsequent infection of dead tissue by bacteria and putrefaction, anaerobes

involves large amount of tissue

Front 63

fat necrosis

Back 63

fat necrosis = lipase action on adipose tissue; pancreatic necrosis

Front 64

ways that damaged ECM cause tissue injury

Back 64

increased destruction of ECM – inflammation/immune responses; lysosomal enzymes

decreased production of ECM –dermatosporaxis; vitaman C deficiencies

excessive production of ECM –healing response for irreversibly damaged tissue; fibrosis forms scar tissue and collagen; permanent damage

deposition of abnormal substances - amyloidosis

Front 65

what is amyloid

Back 65

pink, acellular, amorphous material

fibrillar protein

Front 66

define amyloidosis

Back 66

Amyloidosis = deposition of amyloid with its B-pleated sheet structure, abnormal folding; 95% consists of fibril proteins; 18 forms of amyloid

Front 67

2 forms of amyloid
(AL and AA)

Back 67

Amyloid light chain AL – immunoglobulin light chains, prod by plasma cells

Amyloid associated proteins AA – from serum amyloid-associated protein SAA, produced by liver, acute phase protein in response to inflammation

Front 68

primary amyloidosis

Back 68

Primary amyloidosis = immunologic dyshomeostasis and AL protein; plasma cell neoplasmas like multiple myeloma in bone marrow; not common

Front 69

secondary amyloidosis

Back 69

Secondary amyloidosis = chronic inflammation and AA protein; often systemic; fairly common; cytokines

Front 70

2 kinds of calcification

Back 70

dystrophic
metastatic

Front 71

dystrophic calcification

Back 71

dystrophic calcification = deposition of calcium in necrotic tissue

calcium, phospholipids, and phosphate form microcrystal

indicates tissue damage has occurred

serum calcium normal

Front 72

metastatic calcification

Back 72

metastatic calcification = deposition of calcium in normal, viable tissue

calcium dyshomeostatis secondary to hypercalcemia (hyperparathyroidism, vit D dys, bone neoplasia)

form microcrystal like dystrophic

basement membranes, pleura, kidneys

systemic calcium dyshomeostasis (not tissue dysfunction)

Front 73

major morphologic features of injured tissues (2)

Back 73

cell injury - necrosis

ECM injury - loss of normal architecture by fibrosis, calcification, amyloidosis

Front 74

developmental disease:
due to abnormal ________ or postnatal _________

Back 74

due to abnormal embryogensis or postnatal development

Front 75

congenital

Back 75

manifested at birth

Front 76

acquired

Back 76

apparent later in development

Front 77

developmental disease causes
__% unknown
__% genetic
__% environmental

Back 77

65% unknown (multifactorial)
70% genetic
30% environmental

Front 78

autosomal dominant

Back 78

in every generation but onset later in life

Front 79

autosomal recessive

Back 79

not every generation but onset earlier in life

Front 80

x-linked recessive

Back 80

asymptomatic females transmit to sons

hemophilia

Front 81

Mech that result in abnormal development

Back 81

arrest of inhibition of development
persistence of fetal structures
failure of closure of fetal grooves and fissures
growth in aberrant locations
duplications
lack of coordiation of tissue differentiation

Front 82

amelia

Back 82

limbs absent

Front 83

hemimelia

Back 83

limbs partially absent

Front 84

arthrogryposis

Back 84

limbs abnormally contracted, flexed, rotated

Front 85

chondrodysplasia

Back 85

lack of coordinated bone and joint development

normal appositional growth
abnormal endochondral growth

Front 86

osteopetrosis

Back 86

thick bone

have hemologic problems because no marrow

Front 87

anencephaly

Back 87

absence of brain

Front 88

hydrocephalus

Back 88

hydrocephalus = dilation of lateral ventricles and accumulation of fluid; cerebrum normal but atrophied

Front 89

hydrancephaly

Back 89

hydranencephaly = cerebrum fails to develop properly, absence of cerebral tissue, cerebral hemispheres are cystic cavities; fetal viral infection

Front 90

major causes of metabolic disease (3)

Back 90

genetic
nutrition
hormonal regulation

Front 91

Nutrition
inadequate _____ (3)

Back 91

inadequate diet: deficiency, excess
inadequate uptake
inadequate absorption