Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/662

Click to flip

662 Cards in this Set

  • Front
  • Back
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; Alzheimer’s
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
Barrett’s 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
γ-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
Bruton’s 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
Langerhan’s 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 α 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 γ-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 Starling’s forces
Starling’s 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
Venous thrombus
fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)
Heparin/warfarin
anticoagulants that prevent venous clot formation
Arterial thrombus
endothelial injury; platelets held together by fibrin
Aspirin
prevents platelet thrombus in arteries
Pulmonary thromboembolism
femoral vein site of origin
Systemic thromboembolism
majority from left heart
Fat embolus
long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia
Amniotic fluid embolism
DIC; lanugo hair in maternal pulmonary arteries
Diving
1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue
Decompression sickness
release of N2 gas from tissue with rapid ascent; ischemic damage
Dyspnea, chest pain underwater
pulmonary embolus
Dyspnea, chest pain rising to surface
spontaneous pneumothorax
Hypovolemic shock (blood loss)
↓ CO and LVEDP; ↑ PVR
Cardiogenic shock
↓ CO; ↑ LVEDP and PVR
Septic shock
↑ CO (↑ venous return); ↓ PVR (vasodilation)
Kidneys
most susceptible organ in shock; straight portion proximal tubule most susceptible
Shock complications
ischemic ATN, multiorgan failure, ↑ AG metabolic acidosis
Tumors
parenchyma neoplastic component
Benign tumors
epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)
Carcinoma
epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma
Basal cell carcinoma
invades but does not metastasize
Squamous cell carcinoma
lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix
Adenocarcinoma
distal esophagus → colon, kidney, liver, pancreas, prostate, breast, lung, endometrium
Transitional cell carcinoma
renal pelvis, ureter, bladder
Sarcoma
malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)
Liposarcoma
MC sarcoma in adults
Embryonal rhabdomyosarcoma
MC sarcoma in children
Teratoma
ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
Hamartoma
normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp
Choristoma
normal tissue aberrant tissue location; pancreatic tissue stomach wall
Mixed tumor
different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid
Leukemia
malignancy of stem cells in bone marrow
Lymphoma
malignancy of lymph nodes
Extranodal lymphoma sites
stomach (MC), Peyer’s patches
Malignant tumors
invade and metastasize; benign tumors do not
Upregulate telomerase
increases telomere length; found in all neoplastic cells
Monoclonality
key finding in neoplastic vs. normal cells
E-Cadherin
intercellular adhesion; lose adhesion in malignant cells
Malignant cells
receptors for laminin (basement membrane), fibronectin (ECM)
Invasion enzyme
type IV collagenase (basement membrane)
Angiogenesis
basic fibroblast growth factor, vascular endothelium growth factor
Metastasis
lymphatic, hematogenous, seeding; often more common than primary cancer
Carcinoma
lymph node -> hematogenous
Vessel invading carcinomas
renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
Sarcoma
hematogenous
Seeding
ovarian cancer, periphery lung, CNS via spinal fluid
Sites where metastasis more common primary cancer
lung, bone, brain, liver, adrenal
Sites where primary cancer more common than metastasis
GI tract, kidney, urogenital
Bone metastasis
osteoblastic (radiodense); osteolytic (radiolucent)
Bone sites metastasis
vertebra MC (Batson venous plexus)
Osteoblastic metastasis
prostate cancer; increased serum AP, hypercalcemia
Osteolytic metastasis
breast cancer
EM neurosecretory granules
carcinoid tumors, small cell carcinoma, neuroblastoma
EM thin and thick myofilaments
rhabdomyosarcoma
EM Birbeck granules
histocytic neoplasms (Langerhan’s histiocytosis)
Primary prevention
stop smoking; sun screen; high fiber diet
Cancers in children
leukemia (MC), CNS tumors, Burkitt’s, Ewing’s, neuroblastoma
Cancer vaccine
hepatitis B vaccine; prevents hepatocellular carcinoma
Cancer incidence men
prostate → lung → colorectal
Cancer incidence women
breast → lung → colorectal
Cancer mortality men
lung → prostate → colorectal
Cancer mortality women
lung → breast → colorectal
Gynecologic cancers
endometrium → ovary → cervix
Cervical Pap smear
decreased incidence of cervical cancer; detects cervical dysplasia
Malignant melanoma
fastest increasing in world
Southeast China
nasopharyngeal carcinoma (EBV)
Southeast Asia
hepatocellular carcinoma (HBV + aflatoxin)
Japan
stomach cancer
Africa
Burkitt’s lymphoma, Kaposi sarcoma (HHV-8)
Squamous dysplasia oropharynx, larynx, bronchus, cervix
risk for squamous cell carcinoma (SCC)
Chronic irritation sinus orifices, third degree burn scars
risk for SCC
Actinic (solar) keratosis
risk factor for SCC
Glandular metaplasia of esophagus (Barrett’s)
risk factor for adenocarcinoma
Endometrial hyperplasia
risk factor for adenocarcinoma
Glandular (intestinal) metaplasia of stomach (Helicobacter)
risk factor for adenocarcinoma
Chronic ulcerative colitis
risk factor for adenocarcinoma
Villous adenoma of rectum
risk factor for adenocarcinoma
Tubular adenoma of colon
risk factor for adenocarcinoma
Scar tissue in lung
risk factor for adenocarcinoma
Regenerative nodules in cirrhosis
risk factor for hepatocellular carcinoma
Complete hydatidiform mole
risk factor for choriocarcinoma
Dysplastic mole
MC risk factor for malignant melanoma
UVB light
MC risk factor for BCC, SCC, melanoma
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; Alzheimer’s
Exocrine gland atrophy in CF
duct obstruction by thick secretions
Labile cells
stem cells (skin, marrow, GI tract) →←→⇦à
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
Barrett’s 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
γ-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
Bruton’s 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
Langerhan’s 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 α 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 γ-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 Starling’s forces
Starling’s 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
Venous thrombus
fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)
Heparin/warfarin
anticoagulants that prevent venous clot formation
Arterial thrombus
endothelial injury; platelets held together by fibrin
Aspirin
prevents platelet thrombus in arteries
Pulmonary thromboembolism
femoral vein site of origin
Systemic thromboembolism
majority from left heart
Fat embolus
long bone fractures; delayed symptoms (48 hrs); thrombocytopenia, hypoxemia
Amniotic fluid embolism
DIC; lanugo hair in maternal pulmonary arteries
Diving
1 atmosphere pressure increase with 33 foot descent into water; N2 gas dissolved in tissue
Decompression sickness
release of N2 gas from tissue with rapid ascent; ischemic damage
Dyspnea, chest pain underwater
pulmonary embolus
Dyspnea, chest pain rising to surface
spontaneous pneumothorax
Hypovolemic shock (blood loss)
↓ CO and LVEDP; ↑ PVR
Cardiogenic shock
↓ CO; ↑ LVEDP and PVR
Septic shock
↑ CO (↑ venous return); ↓ PVR (vasodilation)
Kidneys
most susceptible organ in shock; straight portion proximal tubule most susceptible
Shock complications
ischemic ATN, multiorgan failure, ↑ AG metabolic acidosis
Tumors
parenchyma neoplastic component
Benign tumors
epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)
Carcinoma
epithelial origin; squamous cell carcinoma, adenocarcinoma, transitional cell carcinoma
Basal cell carcinoma
invades but does not metastasize
Squamous cell carcinoma
lower lip, oral pharynx, larynx, lung, esophagus, skin, cervix
Adenocarcinoma
distal esophagus → colon, kidney, liver, pancreas, prostate, breast, lung, endometrium
Transitional cell carcinoma
renal pelvis, ureter, bladder
Sarcoma
malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)
Liposarcoma
MC sarcoma in adults
Embryonal rhabdomyosarcoma
MC sarcoma in children
Teratoma
ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
Hamartoma
normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp
Choristoma
normal tissue aberrant tissue location; pancreatic tissue stomach wall
Mixed tumor
different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid
Leukemia
malignancy of stem cells in bone marrow
Lymphoma
malignancy of lymph nodes
Extranodal lymphoma sites
stomach (MC), Peyer’s patches
Malignant tumors
invade and metastasize; benign tumors do not
Upregulate telomerase
increases telomere length; found in all neoplastic cells
Monoclonality
key finding in neoplastic vs. normal cells
E-Cadherin
intercellular adhesion; lose adhesion in malignant cells
Malignant cells
receptors for laminin (basement membrane), fibronectin (ECM)
Invasion enzyme
type IV collagenase (basement membrane)
Angiogenesis
basic fibroblast growth factor, vascular endothelium growth factor
Metastasis
lymphatic, hematogenous, seeding; often more common than primary cancer
Carcinoma
lymph node -> hematogenous
Vessel invading carcinomas
renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
Sarcoma
hematogenous
Seeding
ovarian cancer, periphery lung, CNS via spinal fluid
Sites where metastasis more common primary cancer
lung, bone, brain, liver, adrenal
Sites where primary cancer more common than metastasis
GI tract, kidney, urogenital
Bone metastasis
osteoblastic (radiodense); osteolytic (radiolucent)
Bone sites metastasis
vertebra MC (Batson venous plexus)
Osteoblastic metastasis
prostate cancer; increased serum AP, hypercalcemia
Osteolytic metastasis
breast cancer
EM neurosecretory granules
carcinoid tumors, small cell carcinoma, neuroblastoma
EM thin and thick myofilaments
rhabdomyosarcoma
EM Birbeck granules
histocytic neoplasms (Langerhan’s histiocytosis)
Primary prevention
stop smoking; sun screen; high fiber diet
Cancers in children
leukemia (MC), CNS tumors, Burkitt’s, Ewing’s, neuroblastoma
Cancer vaccine
hepatitis B vaccine; prevents hepatocellular carcinoma
Cancer incidence men
prostate → lung → colorectal
Cancer incidence women
breast → lung → colorectal
Cancer mortality men
lung → prostate → colorectal
Cancer mortality women
lung → breast → colorectal
Gynecologic cancers
endometrium → ovary → cervix
Cervical Pap smear
decreased incidence of cervical cancer; detects cervical dysplasia
Malignant melanoma
fastest increasing in world
Southeast China
nasopharyngeal carcinoma (EBV)
Southeast Asia
hepatocellular carcinoma (HBV + aflatoxin)
Japan
stomach cancer
Africa
Burkitt’s lymphoma, Kaposi sarcoma (HHV-8)
Squamous dysplasia oropharynx, larynx, bronchus, cervix
risk for squamous cell carcinoma (SCC)
Chronic irritation sinus orifices, third degree burn scars
risk for SCC
Actinic (solar) keratosis
risk factor for SCC
Glandular metaplasia of esophagus (Barrett’s)
risk factor for adenocarcinoma
Endometrial hyperplasia
risk factor for adenocarcinoma
Glandular (intestinal) metaplasia of stomach (Helicobacter)
risk factor for adenocarcinoma
Chronic ulcerative colitis
risk factor for adenocarcinoma
Villous adenoma of rectum
risk factor for adenocarcinoma
Tubular adenoma of colon
risk factor for adenocarcinoma
Scar tissue in lung
risk factor for adenocarcinoma
Regenerative nodules in cirrhosis
risk factor for hepatocellular carcinoma
Complete hydatidiform mole
risk factor for choriocarcinoma
Dysplastic mole
MC risk factor for malignant melanoma
UVB light
MC risk factor for BCC, SCC, melanoma
HHV-8
MC risk factor for Kaposi’s sarcoma
EBV
MC risk factor for nasopharyngeal carcinoma
Polycyclic hydrocarbons
MC risk factor for larynx (SCC), lung cancers
Asbestos
MC risk factor for mesothelioma
Polycyclic hydrocarbons
MC risk factor for oral cavity, mid-esophagus SCC
Barrett’s esophagus
MC risk factor for distal esophagus adenocarcinoma
H. pylori
MC risk factor for stomach adenocarcinoma and lymphoma
Tubular adenoma, villous adenoma
MC risk factors for colon adenocarcinoma
HBV and HCV
MC risk factors for hepatocellular carcinoma
Vinyl chloride
MC risk factor for liver angiosarcoma
Gallstones, porcelain gallbladder
MC risk factor for gallbladder adenocarcinoma
Polycyclic hydrocarbons
MC risk factor for pancreas adenocarcinoma
Polycyclic hydrocarbons
MC risk factor for renal cell carcinoma
Polycyclic hydrocarbons
MC risk factor for urinary bladder
HPV + lack of circumcision
MC risk factor for penis SCC
Age
MC risk factor for prostate adenocarcinoma
Cryptorchid testis
MC risk factor for seminoma
Age >50 with excess estrogen exposure
MC risk factor for breast and endometrial carcinoma
HPV 16/18
MC risk factor for vulva, vagina, cervix SCC
DES
MC risk factor for vagina/cervix clear cell carcinoma
Nulliparity
MC risk factor for surface derived ovarian cancer
Complete mole
MC risk factor for choriocarcinoma
Turner syndrome (XO)
MC risk factor for dysgerminoma of ovary
Turner syndrome (XO/XY)
gonadoblastoma of ovary
Ionizing radiation
MC risk factor for papillary cancer of thyroid
Family history (MEN IIa/IIb)
MC risk factor for medullary carcinoma thyroid
Hashimoto’s thyroiditis
MC risk factor for malignant lymphoma thyroid
Ionizing radiation
MC risk factor for osteogenic sarcoma
EBV
MC risk factor for primary CNS lymphoma in AIDS and Burkitt’s lymphoma
Ionizing radiation
MC risk factor for acute/chronic myelogenous leukemia
EBV
MC risk factor for Burkitt’s lymphoma
HTLV-1
MC risk factor for T cell leukemia/lymphoma
Bacterial causes of cancer
H. pylori (stomach adenocarcinoma and lymphoma)
Parasitic causes of cancer
S. hematobium (SCC bladder), C. sinensis (cholangiocarcinoma)
Carcinogenesis
mutations involving regulatory genes
Regulatory genes
proto-oncogenes, suppressor genes, anti-apoptosis genes
Types mutations
point mutation MC, translocation, amplification (↑ copies), overexpression (↑ activity)
Translocations
Burkitt’s t(8;14); CML t(9;22); follicular lymphoma t( 14;18); APL leukemia t( 15;17)
Key cancer genes
TP53 suppressor gene, RAS protooncogene
Point mutation
inactivates suppressor genes (e.g., TP53), activates proto-oncogenes (e.g., RAS)
Amplification
activates ERB-B2
Overexpression
enhances activity of BCL-2
S/S POC
function-growth factor synthesis; mutation-overexpression
ERB-B2 POC
function growth factor receptor; activation bad prognostic sign for breast carcinoma
RAS POC
function-GTP signal transduction; point mutation; 30% of all human cancer
ABL POC
function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML
MYC POC
function nuclear transcription; translocation (8; 14) causing Burkitt’s lymphoma
Inactivation suppressor genes
majority are point mutations; loss of suppression
Sporadic retinoblastoma
two hit theory; two separate point mutations of RB suppressor gene on
AD retinoblastoma
one hit theory; one already inactivated in germ cells
TP53 suppressor gene functions
G,-S phase inhibition, DNA repair, activation BAX apoptosis gene
Inactivation TP 53 suppressor gene
inactivation causes majority of human cancers
RB suppressor gene function
G1-S phase inhibition
Inactivation RB suppressor gene
retinoblastoma, osteogenic sarcoma
APC suppressor gene function
prevents nuclear transcription by catenin
Inactivation APC suppressor gene
familial polyposis (FAP)
BRCA1/2 suppressor genes function
DNA repair Inactivation
BRCA 1/2 suppressor genes
breast, ovarian cancers
BCL-2 function
anti apoptosis gene (keeps cytochrome c in mitochondria)
BCL-2 gene
t(14;18) translocation of heavy chain causes overexpression; follicular B cell lymphoma [think t(14;18) = t(l4;lB) for foLLicular B]
Xeroderma pigmentosum
AR; defect in DNA repair enzymes; ↑ risk for UVB light cancers
Hereditary non-polyposis syndrome (HNPCC)
AD; inactivation DNA mismatch genes; colorectal cancer
Chromosome instability syndromes
AR; susceptibility to DNA damage; leukemias, lymphomas
Examples chromosome instability
Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome
Carcinogens
chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar)
Polycyclic hydrocarbons
key chemical carcinogen (cigarette smoke)
Aflatoxins
produced from Aspergillus; hepatocellular carcinoma
Asbestos
lung cancer, mesothelioma
Thorium dioxide
hepatocellular carcinoma, cholangiocarcinoma
Aniline dyes
transitional cell carcinoma
Vinyl chloride
angiosarcoma of liver
Benzene
leukemia
Cyclophosphamide
transitional cell carcinoma of bladder
EBV
Burkitt’s; CNS lymphoma (AIDS); Hodgkin’s mixed cellularity; nasopharyngeal carcinoma
HBV and HCV
hepatocellular carcinoma
HPV
cervical, penis, and anorectal squamous cancers
HHV-8
Kaposi sarcoma
UVB cancers
basal cell carcinoma, squamous cell carcinoma, malignant melanoma
Key host defense
cytotoxic CD8 T cells (type IV hypersensitivity)
Cachexia
due to tumor necrosis factor-α
Most common anemia
anemia chronic disease
Most common coagulopathy
hypercoagulability
Most common COD in cancer
gram negative infection
Acanthosis nigricans, seborrheic keratoses
possible markers for gastric adenocarcinoma
Clubbing
possible marker for lung cancer
Non-bacterial thrombotic endocarditis mitral valve
possible marker for pancreatic cancer
TNM staging
metastasis more important than nodal involvement
AFP
hepatocellular carcinoma, yolk sac tumors
PSA
prostate cancer
CEA
recurrence colorectal cancer
BJ (Bence-Jones) protein
multiple myeloma
β-human chorionic gonadotropin
choriocarcinoma
Calcitonin
medullary carcinoma thyroid; hypocalcemia
Small cell carcinoma lung
ADH (hyponatremia), ACTH (ectopic Cushing’s)
Renal cell carcinoma
EPO (polycythemia), PTH-related peptide (hypercalcemia)
Hepatocellular carcinoma
EPO (polycythemia), insulin-like factor (hypoglycemia)
Medullary carcinoma of thyroid
calcitonin (hypocalcemia), ACTH (ectopic Cushing’s)
Squamous cell carcinoma of lung
PTH-related peptide (hypercalcemia)