Lectures 1-5 Flashcards
what is cytopathology?
evaluation of cells removed from organ or fluid, usually via needle
describe lymphocyte morphology
large nucleus, barely any cytoplasm
describe plasma cell morphology
nucleus off to the side
describe macrophage morphology
small nucleus, big granular cytoplasm
labile cells
continuously dividing
define hypertrophy
increase in size of cells
causes of physiologic hypertrophy
increased functional demand or hormonal stimulation
increased size of skeletal muscle of weight lifting athlete and uterus during pregnancy are examples of what?
physiologic hypertrophy
enlargement of cardiac muscle due to hypertension is an example of what?
pathologic hypertrophy
define hyperplasia
increase in number of cells
enlargement of female breast at puberty and in pregnancy is an example of what?
physiologic hyperplasia
regeneration of liver after partial resection is an example of what?
physiologic hyperplasia
causes of pathologic hyperplasia
excessive stimulation by growth factors or hormones
what cellular adaptation increases risk for cancer?
pathologic hyperplasia
skin warts and mucosal lesions associated with papilloma virus is an example of what cell adaptation?
pathologic hyperplasia
what organ undergoes both hyperplasia and hypertrophy?
uterus
define atrophy
decrease in size of cell
define metaplasia
one cell type is replaced by another cell type that is better able to handle stress
Barrett esophagus
-example of metaplasia -squamous epithelium becomes glandular epithelium (stomach cells), protects against reflux of stomach acid -predisposes to development of adenocarcinoma
what is the difference between hypoxia and ischemia?
hypoxia is the inadequate oxygenation of blood and ischemia is lack of blood supply to a site
in what type of cell injury do you see karyorrhexis and karyolysis?
necrosis
in what type of cell injury do you see nuclear shrinkage?
necrosis
what kind of necrosis results from hypoxic/anoxic injury due to ischemia?
coagulative
cause of coagulative necrosis
hypoxic/anoxic injury due to ischemia
where does coagulative necrosis occur?
in all solid organs except the brain
dead cells with intact outlines but smudgy appearance, no nuclei –> what kind of necrosis?
coagulative
common causes of liquefactive necrosis
1) bacterial/fungal infections 2) brain infarcts
dead cells with no outlines, karyorrhexis (fragments of nuclei) –> what kind of necrosis?
liquefactive
white/yellow raised focal abscesses on surface of organ –> what kind of necrosis?
liquefactive
granuloma: what it looks like, what kind of necrosis?
amorphous granular material surrounded by a border of inflammatory cells; caseous
term used for ischemic coagulative necrosis of lower or upper extremity
gangrenous necrosis
wet gangrene
ischemic coagulative necrosis with bacterial infection, also has liquefactive characteristics
necrosis commonly seen in acute pancreatitis
fat
necrosis associated with vasculitis syndromes
fibrinoid
cell death in which plasma membrane stays intact
apoptosis
intrinsic apoptosis pathway: mechanism
Bcl-2 proteins increase permeability of the mitochondria and allow cytochrome C to enter cytoplasm –> caspase activation
common endpoint of intrinsic and extrinsic apoptosis pathways
both activate initiator caspases –> executioner caspases –> break down of cytoskeleton –> apoptotic body
two types of reversible cell injury
fatty change, hydropic change/vacuolar degeneration
when does fatty change happen?
when there is toxic and hypoxic injury in cells dependent on fat metabolism
common example of fatty change
fatty liver secondary to excess alcohol
mechanism of fatty change in fatty liver secondary to excess alcohol
hepatocytes are injured –> intracellular accumulation of triglycerides –> liver enlargement and increased liver enzymes (they leak from injured hepatocytes)
hydropic change/vacuolar degeneration: cause, why do vacuoles appear, what happens to cell size
results from failure of membrane pump to maintain homeostasis so membrane blebs; vacuoles appear in cells corresponding to distended ER; cell swells
what happens when there is mitochondrial damage?
ATP depletion, influx of calcium, anaerobic glycolysis, increased production of ROS and pro-apoptotic proteins
effects of influx of calcium in a cell
ER swelling, membrane and nuclear damage, increased mitochondrial permeability and therefore less ATP
why is there clumping of nuclear chromatin after mitochondrial damage?
mitochondrial damage causes increased anaerobic glycolysis –> decreased pH –> clumping of nuclear chromatin
does ischemia or hypoxia injure tissues faster? why?
ischemia (decreased blood flow), because there is no delivery of substrates for glycolysis (in hypoxia anaerobic glycolysis continues)
what cell type is particularly sensitive to lack of oxygen?
neurons
reperfusion injury: mechanism, in what organs does it frequently occur?
ischemia causes incomplete reduction of oxygen, so when oxygen is restored it allows for production of free radicals which lead to tissue damage; brain and heart
lipofuscin: what is it, in what organs is it found?
indigestible material resulting from lipid peroxidation, “wear and tear” pigment that occurs predominantly with aging; heart, liver, brain
Tay-Sachs disease: type of disease, mechanism
lysosomal storage disease; increased gangliosides because of lack of enzyme to degrade it, leads to decrease in cognitive function and death
what happens to mitochondria during starvation and alcohol consumption?
starvation: atrophy alcohol: enlarge
example of disease with cytoskeleton abnormalities and its mechanism
Alzheimer’s: accumulations of neurofibrillary tangles –> apoptosis
hemosiderin: what is it, where is it found
hemoglobin-derived pigment containing iron; occurs locally where there has been hemorrhage. if a patient has many blood transfusions systemic deposition can occur
characteristics of dystrophic pathologic calcification
occurs in dying tissues, typically inflammatory process, normal serum calcium
what kind of pathologic calcification occurs on aortic valves in the elderly?
dystrophic
what kind of pathologic calcification occurs with atheromas?
dystrophic
characteristics of metastatic pathologic calcification
occurs in normal tissues because of hypercalcemia due to increased parathyroid hormone, destruction of bone, or renal failure
what kind of pathologic calcification occurs with renal failure?
metastatic
what kind of pathologic calcification occurs with increased parathyroid hormone?
metastatic
CD4 T cells recruit/activate what cells and by what mechanisms?
macrophages and B cells by cytokine secretion or CD40:CD40L interaction
clonal expansion of T cells is driven by what cytokine?
IL-2
role of TH1 cells
produces IFN-gamma, defends against intracellular microbes
role of TH2 cells
produce IL-4, -5, -13, allergies
role of TH17 cells
produce IL-17, -22, chemokines, defends against extracellular bacteria, fungi
activates classical complement pathway
IgM and IgG
role of IgM
low affinity, activates classical complement pathway
role of IgG
main workhorse, abundant in blood, opsonize antigens, activates classical complement pathway, ADCC
antibody responsible for ADCC
IgG
role of IgA
produced in gut and respiratory tract, neutralize mucosal microbes and toxins
role of IgE
allergy via mast cell degranulation, parasites
starting point of alternative complement pathway
C3b
live attenuated vaccination induces what type of response?
T cell
inactivated vaccination induces what type of response?
B cell
central tolerance: mechanism
after positive selection, any immature T/B cells that recognize high avidity self antigens presented on MHC are killed through apoptosis
peripheral tolerance mechanisms
apoptosis via Fas/Fas ligand, anergy by APCs that lack costimulatory molecules, suppression by Tregs
APECED: mechanism
defect in AIRE gene which normally induces expression of self antigens by thymic cells to lead to the deletion of self-reactive T cells
low calcium, low PTH, low cortisol
APECED
skin bronzing, fungal infections
APECED
characterized by autoimmune adrenal and parathyroid disease
APECED
ALPS: mechanism
mutations in Fas or Fas ligand; Fas normally transmits pro-apoptotic signals that result in lymphocyte death
diffuse lymphadenopathy, splenomegaly, hemolytic anemia, high double negative T cells, hypergammaglobulinemia
ALPS
IPEX: mechanism
mutation in Foxp3 –> loss of T regulatory cells
IBD, severe eczema and food allergies, hemolytic anemia, high IgG and IgE
IPEX
type 1 hypersensitivity: mechanism, examples
immediate hypersensitivity, IgE-mediated, requires TH2 cells; allergic rhinitis, asthma, eczema, food allergies
type 2 hypersensitivity: mechanism, examples
antibody-mediated hypersensitivity: antibodies are made to self proteins –> complement activation (which may lead to lysis of RBCs), crosslinking of Fc receptors on macrophage/neutrophils, phagocytosis (of platelets in ITP); myasthenia gravis, Grave’s disease, acute rheumatic fever
acute rheumatic fever: mechanism, hypersensitivity type
virulence factors expressed by S. pyogenes are structurally similar to heart muscle –> antibodies are made against heart muscle; 2
JONES criteria: what disease and what does it stand for
acute rheumatic fever: joints, heart, nodules, erythema marginatum, Syndenham’s chorea (major manifestations)
antibodies against proteins in intracellular junctions of epidermal cells causing skin vesicles
pemphigus vulgaris
pemphigus vulgaris: mechanism, hypersensitivity type
antibodies against proteins in intracellular junctions of epidermal cells causing skin vesicles; 2
antibodies against basement membranes of kidney glomeruli and lung alveoli causing nephritis and lung hemorrhages
Goodpasture’s syndrome
Goodpasture’s syndrome: mechanism, hypersensitivity type
antibodies against basement membranes of kidney glomeruli and lung alveoli causing nephritis and lung hemorrhages; 2
antibodies against acetylcholine receptor
myasthenia gravis
myasthenia gravis: mechanism, hypersensitivity type
antibodies against acetylcholine receptor; 2
antibodies against TSH receptor
Graves’ disease
Graves’ disease: mechanism, hypersensitivity type
antibodies against TSH receptor; 2
antibodies against intrinsic factor of gastric parietal cells causing macrocytic anemia
pernicious anemia
pernicious anemia: mechanism, hypersensitivity type
antibodies against intrinsic factor of gastric parietal cells causing macrocytic anemia; 2
treatment of antibody-mediated diseases
IVIG, corticosteroids (Prednisone), rituximab (kills B cells), plasmapharesis
type 3 hypersensitivity: what is it called?
immune complex-mediated
11 criteria of SLE
4 skin-related: discoid rash, malar rash, photosensitivity, oral/nasal ulcers 4 organ-related (-itises): arthritis, serositis, cerebritis, nephritis 3 lab: ANA, immune (dsDNA, anti-Sm), autoimmune cytopenias must have 4 out of 11 to be diagnostic
antibodies against hepatitis B surface antigen causing vasculitis
polyarteritis nodosa
polyarteritis nodosa: mechanism, hypersensitivity type
antibodies against hepatitis B surface antigen causing vasculitis; 3
antibodies against streptococcal cell wall antigens causing nephritis
poststreptococcal glomerulonephritis
poststreptococcal glomerulonephritis: mechanism, hypersensitivity type
antibodies against streptococcal cell wall antigens causing nephritis; 3
type 4 hypersensitivity: what is it called?
immediate type (T cells)
high ESR/CRP
rheumatoid arthritis
rheumatoid arthritis: mechanism
T cells in synovial space activate monocytes, macrophages, and synovial fibroblasts which then release IL-1, IL-6, and TNF
rash on eyelids, bridge of nose, cheeks, scaly plaques on knuckles, MCP, elbows, knees, toes, proximal muscle weakness, dilation of capillaries in nail bed, high AST, ALT, CK
dermatomyositis
dermatomyositis: symptoms
rash on eyelids, bridge of nose, cheeks, scaly plaques on knuckles, MCP, elbows, knees, toes, proximal muscle weakness, dilation of capillaries in nail bed, high AST, ALT, CK
dermatomyositis: mechanism
perivascular inflammatory infiltrate with CD4 T cells, necrosis of muscle in periphery (perifascicular atrophy)
differences between polymyositis and dermatomyositis
polymyositis has diffuse muscle fiber death next to normal fibers (damage is spotty throughout muscle, not perifascicular) and is mediated by CD8 T cells not CD4
chronic granulomatous disease: mechanism
absence of respiratory burst in neutrophils due to defect in an NADPH oxidase subunit
absence of respiratory burst in neutrophils due to defect in an NADPH oxidase subunit
chronic granulomatous disease
infant with adenopathy, liver abscesses, infection with catalase-positive organisms (Staph, Aspergillus, Nocardia)
chronic granulomatous disease
chronic granulomatous disease: clinical presentation
infant with adenopathy, liver abscesses, infection with catalase-positive organisms (Staph, Aspergillus, Nocardia)
diagnostic test for chronic granulomatous disease
dihyrorhodamine (DHR) test
leukocyte adhesion deficiency: mechanism
mutation in common beta chain of LFA-1 preventing leukocyte adhesion to endothelium
skin ulcers without pus, high neutrophil count
leukocyte adhesion deficiency
leukocyte adhesion deficiency: clinical presentation
skin ulcers without pus, high neutrophil count
late complement deficiency: mechanism
deficiency in C5-C9 which form the membrane attack complex, leads to increased susceptibility to Neisserial infections
increased susceptibility to Neisserial infections
late complement deficiency
X-Linked Agammaglobulinemia (XLA): mechanism
mutation in Btk = no B cells
X-Linked Agammaglobulinemia (XLA): clinical presentation
early onset recurrent otitis, sinusitis, pneumonia
bronchiectasis: what it is, which diseases it is seen in
widening of bronchi due to recurrent infections; X-Linked Agammaglobulinemia (XLA) and Common Variable Immunodeficiency (CVID)
difference between XLA and CVID
XLA is early onset, CVID can be diagnosed at any age
common variable immunodeficiency (CVID): diagnosis
low IgG AND low IgA or IgM
low IgG AND low IgA or IgM
CVID
CVID cause of death
pulmonary disease
why can deficiency in IgA cause false positive pregnancy tests?
increased incidence of heterophile antibodies
specific antibody deficiency: mechanism
developmental delay in antibody response to polysaccharide antigens
specific antibody deficiency: clinical presentation
“abnormal” specific antibody response to immunization (especially polysaccharide antigens); recurrent sinopulmonary infections; normal IgG, IgA, IgM, normal T cell function
X-linked SCID: mechanism
mutation in common gamma-chain of IL-2 receptor (shared component with other IL receptors) = lack of T cells and NK cells, B cells present but not functional
mutation in common gamma-chain of IL-2 receptor
X-linked SCID
SCID: clinical presentation
onset in infancy (4-5 mo), pneumonia, otitis media, thrush, intractable diarrhea, failure to thrive
screening test for SCID; describe
TRECs are a surrogate marker for numbers of normal, naive T cells and is low for all forms of SCID
onset in infancy (4-5 mo), pneumonia, otitis media, thrush, intractable diarrhea, failure to thrive
SCID
DiGeorge syndrome: mechanism
microdeletion in chromosome 2q11.2: field defect first to sixth pharyngeal pouchs; deletion of TBX1 underlies many of the abnormalities
DiGeorge syndrome: clinical presentation
CATCH22 mnemonic: cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, 22nd chromosome
cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia
DiGeorge syndrome
all infants with congenital heart disease/significant heart defects should be tested for what?
DiGeorge syndrome
DiGeorge syndrome: diagnostic test
chromosome microarray/DNA duplication deletion test
