Goljan 1 - Goljan Flashcards
PO2
driving force for diffusion of O2 into tissue
SaO2
percent heme groups occupied by O2
Cyanosis
decreased O2 saturation (SaO2); O2 content
Oxygen
electron acceptor in oxidative pathway
Hypoxia
inadequate O2 leads to ATP depletion
Ischemia
decreased arterial (or venous) blood flow
Respiratory acidosis
retention of CO, always decreases PaO2
Ventilation defect
impaired delivery of O2 to alveoli; intrapulmonary shunting of blood (e.g., RDS)
Perfusion defect
absent blood flow to alveoli; increased alveolar dead space (e.g., pulmonary embolus)
Diffusion defect
O2 cannot cross alveolar-capillary interface; interstitial lung disease (e.g., sarcoidosis)
Methemoglobin
? SaO2; heme Fe+3; oxidizing agents (sulfur/nitro drugs); Rx with IV methylene blue
Clinical methemoglobinemia
cyanosis not corrected by O2; chocolate colored blood
Carbon monoxide
? SaO2; left-shift O2 binding curve; inhibits cytochrome oxidase
Causes carbon monoxide poisoning
car exhaust, space heaters, smoke inhalation
S/S carbon monoxide poisoning
headache; cherry red color skin
Cyanide
inhibits cytochrome oxidase; systemic asphyxiant
Carbon monoxide + cyanide poisoning
house fires
Left-shifted O2 curve
? 2, 3 BPG, carbon monoxide, alkalosis, HbF, methemoglobin, hypothermia
Right-shifted O2 curve
? 2, 3 BPG, high altitude, acidosis, fever
High altitude
respiratory alkalosis enhances glycolysis; ? synthesis 2,3 BPG
Mitochondrial poisons
damages membrane and drains off protons; alcohol, salicylates
Uncoupling agents in mitochondria
drain off protons; dinitrophenol, thermogenin (brown fat)
Complication mitochondrial poisons/uncoupling agents
hyperthermia
Decreased ATP
impaired Na+/K+ ATPase pump (cellular swelling); reversible
Anaerobic glycolysis
ATP synthesis in hypoxia; lactate ? intracellular pH, denatures proteins
Irreversible injury hypoxia
membrane/mitochondrial damage
Mitochondrial damage
release cytochrome c activates apoptosis
Irreversible injury hypoxia
? cytosolic Ca2+ activates phospholipase, proteases, endonuclease
Free radicals
unpaired electron in outer orbit; damage cell membranes and DNA
Free radicals
superoxide, hydroxyl, peroxide, drugs (acetaminophen)
Superoxide dismutase
neutralizes superoxide
Glutathione
neutralizes peroxide, drug FRs
Catalase
neutralizes peroxide
Lipofuscin
indigestible lipid of lipid peroxidation; brown pigment increased in atrophy and FR damage
Reperfusion injury in heart
superoxide FRs + calcium
Mitochondrial injury
cytochrome c in cytosol initiates apoptosis
SER hyperplasia
alcohol, barbiturates, phenytoin
Complications SER hyperplasia
increases drug metabolism (e.g., oral contraceptives); low vitamin D
Chediak-Higashi
membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles
Chediak-Higashi
AR; giant lysosomes
I cell disease
absent enzyme marker in Golgi apparatus (mannose 6-phosphate); empty lysosomes
Rigor mortis
stiff muscles after death due to ATP depletion
Fatty change in liver
MCC alcohol (increase in NADH); DHAP ? G3P ? TG
Fatty change in liver
VLDL pushes nucleus to side
Causes fatty change
? synthesis TG/FAs, beta-oxidation of FAs, synthesis apoproteins/release VLDL
Fatty change in kwashiorkor
? synthesis of apoproteins
Ferritin
primary iron storage protein; soluble in blood; serum level reflects marrow storage iron
Hemosiderin
insoluble ferritin degradation product visible with Prussian blue stain
Atrophy
reduction in cell/tissue mass by either loss or cell shrinkage
Brain atrophy
ischemia; AlzheimerÕs
Exocrine gland atrophy in CF
duct obstruction by thick secretions
Labile cells
stem cells (skin, marrow, GI tract) ?????
Stable cells
in G0 phase (smooth muscle, hepatocytes); can enter cell cycle (growth factors, hormones)
Permanent cells
cannot replicate; cardiac/striated muscle; neurons
Hypertrophy
increase in cell size (structural components, DNA)
LVH
increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis)
RVH
pulmonary hypertension
Bladder smooth muscle hypertrophy
prostate hyperplasia constricts urethra
Removal of kidney
hypertrophy of remaining kidney
Hyperplasia
increase in number of cells
Endometrial hyperplasia
unopposed estrogen (obesity, taking estrogen)
RBC hyperplasia
increased EPO (blood loss, ectopic secretion, high altitude)
Prostate hyperplasia
increased dihydrotestosterone (DHEA)
Gynecomastia
hyperplasia male breast tissue; normal in newborn, adolescent, elderly
Metaplasia
one adult cell type replaces another cell type
Squamous metaplasia in bronchus
smoking
Intestinal metaplasia in stomach
Paneth cells, goblet cells; H pylori chronic atrophic gastritis
Squamous metaplasia bladder
Schistosoma hematobium infection
BarrettÕs esophagus
glandular metaplasia of distal esophagus; due to GERD
Dysplasia
atypical hyperplasia and metaplasia are precursors for cancer
Squamous dysplasia in cervix
human papilloma virus
Squamous dysplasia in bronchus
smoking
Necrosis
death of groups of cells
Coagulation necrosis
preservation of structural outline (due to ? lactic acid)
Infarction
pale (e.g., heart, kidney); hemorrhagic (e.g., lung, small bowel); dry gangrene
Liquefactive necrosis
brain infarct, bacterial infections; wet gangrene
Caseous necrosis
variant coagulation necrosis; granulomas due to TB/systemic fungi
Granulomas
activated macrophages (epithelioid cells); multinucleated giant cells; CD4 TH1 cells
Epithelioid cells
?-interferon released by CD4 T cells activates macrophages
Multinucleated giant cells
fusion of epithelioid cells
Granulomas
type IV hypersensitivity
Enzymatic fat necrosis
associated with pancreatitis; soap formation (Ca2+ + fatty acids)
Fibrinoid necrosis
necrosis of immune reactions (immune vasculitis/endocarditis)
Postmortem necrosis
autolysis; no inflammatory reaction
Dystrophic calcification
calcification of damaged tissue; normal serum calcium
Dystrophic calcification
pancreatitis; atherosclerotic plaque
Metastatic calcification
calcification of normal tissue; increased serum calcium or phosphorus
Nephrocalcinosis
metastatic calcification of collecting tubule basement membranes
S/S nephrocalcinosis
polyuria due to nephrogenic diabetes insipidus; renal failure
Apoptosis
gene regulated individual cell death
Signals activating apoptosis
mullerian inhibitory factor, tumor necrosis factor, hormone withdrawal
Signal modulators of apoptosis
TP53 suppressor gene, BCL-2 genes
BCL-2 genes
anti-apoptosis gene; prevents cytochrome c from leaving mitochondria
Caspases
responsible for enzymatic cell death in apoptosis; proteases and endonucleases
Markers of apoptosis
eosinophilic cytoplasm, pyknotic (ink dot) nucleus
Apoptosis
loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells
Histamine
key chemical in acute inflammation; mast cell; arteriole vasodilation; ? venular permeability
Rubor acute inflammation
redness; arteriole vasodilation (histamine)
Calor acute inflammation
heat; arteriole vasodilation (histamine)
Tumor acute inflammation
swelling; ? vessel permeability (histamine)
Dolor acute inflammation
pain; bradykinin, PGE
Acute inflammation
neutrophil dominant; ? IgM
Initial vessel events
transient vasoconstriction ? arteriolar vasodilation ? ? venular permeability
Neutrophil rolling acute inflammation
due to selectins
Integrins
neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination
CD11/CD18
markers for integrins
Endothelial cell adhesion molecules
activated by IL-1 and TNF
ICAM
intercellular adhesion molecule
VCAM
vascular cell adhesion molecule Leukocyte adhesion molecule defect
Activation neutrophil adhesion molecules
neutrophilic leukocytosis; corticosteroids
Activation neutrophil adhesion molecules
neutropenia; endotoxins
Chemotaxis
directed movement; C5a and LTB4
Opsonizing agents
IgG, C3b; enhance phagocytosis
Neutrophils, monocytes, macrophages
receptors for IgG, C3b
O2-dependent MPO system
most potent microbicidal system; neutrophils, monocytes
ProductionofsuperoxidefromO2
NADPH oxidase with NADPH cofactor; produces respiratory burst
Nitro blue tetrazolium (NBT)
test for respiratory burst
Superoxide dismutase
converts superoxide to peroxide
Myeloperoxidase
lysosomal enzyme that combines peroxide + Cl to form bleach (HOCl)
Microbicidal defects
chronic granulomatous disease childhood (XR), myeloperoxidase deficiency (AR)
Chronic granulomatous disease
absent NADPH oxidase; no respiratory burst
Chronic granulomatous disease
Staphylococcus aureus not killed (catalase positive)
Chronic granulomatous disease
Streptococcus killed (catalase negative)
Myeloperoxidase deficiency
AR; respiratory burst present; no bleach produced
Opsonization defect
BrutonÕs agammaglobulinemia (XR, decreased IgG)
Phagocytosis defect
Chediak-Higashi (see cell injury); also has defect in microtubule polymerization
COX inhibitors
non-steroidals (non-selective), selective COX-2 inhibitors
PGE2
vasodilation, fever
PGI2
vasodilator; prevent platelet aggregation
Nitric oxide
vasodilator; FR gas from conversion arginine to citrulline
IL-1 and TNF
fever, synthesis acute phase reactants in liver, leukocytosis
IL-6
stimulated by IL-1; stimulates synthesis of acute phase reactants
Acute phase reactants
fibrinogen, ferritin, C-reactive protein
Bradykinin
kinin produced in conversion of factor XII to factor XI
Bradykinin
pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors
Anaphylatoxins
C3a and C5a; directly stimulate mast cell release of histamine
Prostaglandin I2
synthesized by endothelial cells; vasodilator, inhibits platelet aggregation
Lipoxygenase
hydroxylation of arachidonic acid
Zileuton
inhibits lipoxygenase
Zafirlukast, montelukast
block lipoxygenase receptor
LTC4, -D4, -E4
bronchoconstrictors
TXA2
synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction
Dipyridamole
inhibits thromboxane synthase
Corticosteroids
inhibits phospholipase A2, activation neutrophil adhesion molecules
Corticosteroids
neutrophilic leukocytosis, lymphopenia, eosinopenia
Fever
right shift OBC; hostile to bacterial/viral replication
Chronic inflammation
monocyte/macrophage; ? IgG; repair by fibrosis
Granuloma
cellular immunity; macrophages interact with TH1 class cells (memory cells)
Positive PPD
LangerhanÕs cells process PPD and interact with TH1 class cells
Suppurative inflammation
abscess; Staphylococcus aureus (coagulase)
Cellulitis
subcutaneous inflammation; Streptococcus pyogenes (hyaluronidase)
Pseudomembranous inflammation
toxins from Corynebacterium diphtheriae, Clostridium difficile
Cell cycle
key checkpoint G1 to S phase
TP53 and RB suppressor genes
arrests cell in G1 phase for DNA repair or apoptosis
BAX gene
stimulates apoptosis; activated by TP53 suppressor gene if too much DNA damage
Extracellular matrix
basement membrane, interstitial matrix
Complete restoration
cell must be capable of duplication, no damage to basement membrane
Scar tissue
end-product of repair by connective tissue
Collagen
triple helix of cross-linked ? chains
Collagen
cross-links at points of hydroxylation (lysyl oxidase) increase tensile strength
Type I collagen
bones, tendons
Type II collagen
early wound repair
Type IV collagen
basement membrane
Type X collagen
epiphyseal plate
Laminin
key basement membrane glycoprotein
Fibronectin
key interstitial matrix glycoprotein
Angiogenesis in repair
basic fibroblast growth factor, vascular endothelial growth factor
Key event in wound repair
granulation tissue formation; fibronectin responsible
Granulation tissue
becomes scar tissue
Collagenases
zinc cofactor (metalloprotease); type III collagen replaced by type I collagen
Tensile strength of healed wound
80% original strength
Inhibition wound healing
infection (MCC S. aureus), zinc deficiency, DM
Ehlers-Danlos syndrome
defects in collagen synthesis and structure; hyperelasticity
Scurvy
? collagen tensile strength by decreasing cross-links at points of hydroxylation
Keloid
excessive type III collagen; common in blacks
Pyogenic granuloma
exuberant granulation tissue; bleeds when touched
Healing by primary intention
clean wound; appose wound margins with suture
Healing by secondary intention
infected wound; leave wound open; myofibroblasts important
Liver injury
regenerative nodules; abnormal cytoarchitecture
Lung injury
type II pneumocyte repair cell
CNS injury
astrocyte and microglial cell repair cells; gliosis
WBC alterations in acute inflammation
neutrophilic leukocytosis, left shift, toxic granulation
Erythrocyte sedimentation rate
increased fibrinogen enhances rouleaux
C-reactive protein
indicator of acute inflammation and inflammatory atheromatous plaque
Polyclonal gammopathy
diffuse ? of ?-globulins; ? IgG; chronic inflammation
Total body water
ECF (plasma, interstitial fluid) + ICF (cytosol)
Osmosis
H20 shift between ECF and ICF; controlled by serum Na+ and glucose
Edema
increased fluid in interstitial space or body cavities; transudate, exudate, lymph
Transudate
protein and cell-poor fluid in interstitial space/body cavity; alteration StarlingÕs forces
StarlingÕs forces
oncotic pressure (albumin) keeps fluid in vessels, hydrostatic pressure pushes fluid out
Pitting edema
decreased oncotic pressure and/or increased hydrostatic pressure
? Hydrostatic pressure
pulmonary edema in LHF; pitting edema of legs in RHF; portal hypertension
Renal retention sodium and water
? hydrostatic pressure and ? oncotic pressure
Causes of renal retention of sodium/water
? cardiac output (activation RAA system), primary renal disease
? Oncotic pressure (hypoalbuminemia)
kwashiorkor; nephrotic syndrome; cirrhosis
Ascites in cirrhosis
? oncotic pressure, ? hydrostatic pressure
Exudate
protein and cell rich (pus); acute inflammation with ? vessel permeability
Lymphedema
radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor)
Thrombus
endothelial injury, stasis, hypercoagulability