2,166 terms

Goljan HY

driving force for diffusion of O2 into tissue
percent heme groups occupied by O2
decreased O2 saturation (SaO2); O2 content
electron acceptor in oxidative pathway
inadequate O2 leads to ATP depletion
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)
↓ 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
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
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
neutralizes peroxide, drug FRs
neutralizes peroxide
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
membrane protein defect in transferring lysosomal enzymes to phagocytic vacuoles
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
primary iron storage protein; soluble in blood; serum level reflects marrow storage iron
insoluble ferritin degradation product visible with Prussian blue stain
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
increase in cell size (structural components, DNA)
increased preload (valve regurgitation), increased afterload (hypertension, aortic stenosis)
pulmonary hypertension
Bladder smooth muscle hypertrophy
prostate hyperplasia constricts urethra
Removal of kidney
hypertrophy of remaining kidney
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)
hyperplasia male breast tissue; normal in newborn, adolescent, elderly
one adult cell type replaces another cell type
Squamous metaplasia in bronchus
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
atypical hyperplasia and metaplasia are precursors for cancer
Squamous dysplasia in cervix
human papilloma virus
Squamous dysplasia in bronchus
death of groups of cells
Coagulation necrosis
preservation of structural outline (due to ↑ lactic acid)
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
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
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
metastatic calcification of collecting tubule basement membranes
S/S nephrocalcinosis
polyuria due to nephrogenic diabetes insipidus; renal failure
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
responsible for enzymatic cell death in apoptosis; proteases and endonucleases
Markers of apoptosis
eosinophilic cytoplasm, pyknotic (ink dot) nucleus
loss Mullerian epithelium in male fetus; thymus involution; killing cancer cells
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
neutrophil adhesion molecules; C5a and leukotriene B, activate; neutrophil margination
markers for integrins
Endothelial cell adhesion molecules
activated by IL-1 and TNF
intercellular adhesion molecule
vascular cell adhesion molecule Leukocyte adhesion molecule defect
Activation neutrophil adhesion molecules
neutrophilic leukocytosis; corticosteroids
Activation neutrophil adhesion molecules
neutropenia; endotoxins
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
NADPH oxidase with NADPH cofactor; produces respiratory burst
Nitro blue tetrazolium (NBT)
test for respiratory burst
Superoxide dismutase
converts superoxide to peroxide
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
vasodilation, fever
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
stimulated by IL-1; stimulates synthesis of acute phase reactants
Acute phase reactants
fibrinogen, ferritin, C-reactive protein
kinin produced in conversion of factor XII to factor XI
pain, vasodilator, vessel permeability; cough/angioedema, ACE inhibitors
C3a and C5a; directly stimulate mast cell release of histamine
Prostaglandin I2
synthesized by endothelial cells; vasodilator, inhibits platelet aggregation
hydroxylation of arachidonic acid
inhibits lipoxygenase
Zafirlukast, montelukast
block lipoxygenase receptor
LTC4, -D4, -E4
synthesized by platelets; platelet aggregation, vasoconstriction, bronchoconstriction
inhibits thromboxane synthase
inhibits phospholipase A2, activation neutrophil adhesion molecules
neutrophilic leukocytosis, lymphopenia, eosinopenia
right shift OBC; hostile to bacterial/viral replication
Chronic inflammation
monocyte/macrophage; ↑ IgG; repair by fibrosis
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)
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
triple helix of cross-linked α chains
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
key basement membrane glycoprotein
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
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
↓ collagen tensile strength by decreasing cross-links at points of hydroxylation
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)
H20 shift between ECF and ICF; controlled by serum Na+ and glucose
increased fluid in interstitial space or body cavities; transudate, exudate, lymph
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
protein and cell rich (pus); acute inflammation with ↑ vessel permeability
radical mastectomy; filariasis; inflammatory carcinoma (lymphatics plugged by tumor)
endothelial injury, stasis, hypercoagulability
Venous thrombus
fibrin clot with entrapped RBCs, WBCs, platelets; deep veins below knee (stasis)
anticoagulants that prevent venous clot formation
Arterial thrombus
endothelial injury; platelets held together by fibrin
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
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)
most susceptible organ in shock; straight portion proximal tubule most susceptible
Shock complications
ischemic ATN, multiorgan failure, ↑ AG metabolic acidosis
parenchyma neoplastic component
Benign tumors
epithelial (e.g., adenoma) or connective tissue (e.g., lipoma, leiomyoma)
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
distal esophagus → colon, kidney, liver, pancreas, prostate, breast, lung, endometrium
Transitional cell carcinoma
renal pelvis, ureter, bladder
malignancy of connective tissue origin; e.g., osteogenic sarcoma (bone)
MC sarcoma in adults
Embryonal rhabdomyosarcoma
MC sarcoma in children
ectoderm, endoderm, mesoderm derivatives; bone/teeth visible on x-ray
normal tissue, normal site; bronchial hamartoma, Peutz Jeghers polyp
normal tissue aberrant tissue location; pancreatic tissue stomach wall
Mixed tumor
different morphologic patterns, same germ cell layer; pleomorphic adenoma parotid
malignancy of stem cells in bone marrow
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
key finding in neoplastic vs. normal cells
intercellular adhesion; lose adhesion in malignant cells
Malignant cells
receptors for laminin (basement membrane), fibronectin (ECM)
Invasion enzyme
type IV collagenase (basement membrane)
basic fibroblast growth factor, vascular endothelium growth factor
lymphatic, hematogenous, seeding; often more common than primary cancer
lymph node -> hematogenous
Vessel invading carcinomas
renal cell carcinoma (renal vein, vena cava), hepatocellular carcinoma
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
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)
stomach cancer
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
MC risk factor for Kaposi's sarcoma
MC risk factor for nasopharyngeal carcinoma
Polycyclic hydrocarbons
MC risk factor for larynx (SCC), lung cancers
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
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
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
MC risk factor for vagina/cervix clear cell carcinoma
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
MC risk factor for primary CNS lymphoma in AIDS and Burkitt's lymphoma
Ionizing radiation
MC risk factor for acute/chronic myelogenous leukemia
MC risk factor for Burkitt's lymphoma
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)
mutations involving regulatory genes
Regulatory genes
proto-oncogenes, suppressor genes, anti-apoptosis genes
Types mutations
point mutation MC, translocation, amplification (↑ copies), overexpression (↑ activity)
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)
activates ERB-B2
enhances activity of BCL-2
function-growth factor synthesis; mutation-overexpression
function growth factor receptor; activation bad prognostic sign for breast carcinoma
function-GTP signal transduction; point mutation; 30% of all human cancer
function-non-receptor tyrosine kinase activity; translocation (9;22) causing CML
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
chemicals (MC), viruses, radiation, H. pylori, physical (squamous cancer in bum scar)
Polycyclic hydrocarbons
key chemical carcinogen (cigarette smoke)
produced from Aspergillus; hepatocellular carcinoma
lung cancer, mesothelioma
Thorium dioxide
hepatocellular carcinoma, cholangiocarcinoma
Aniline dyes
transitional cell carcinoma
Vinyl chloride
angiosarcoma of liver
transitional cell carcinoma of bladder
Burkitt's; CNS lymphoma (AIDS); Hodgkin's mixed cellularity; nasopharyngeal carcinoma
hepatocellular carcinoma
cervical, penis, and anorectal squamous cancers
Kaposi sarcoma
UVB cancers
basal cell carcinoma, squamous cell carcinoma, malignant melanoma
Key host defense
cytotoxic CD8 T cells (type IV hypersensitivity)
due to tumor necrosis factor-α
Most common anemia
anemia chronic disease
Most common coagulopathy
Most common COD in cancer
gram negative infection
possible marker for lung cancer
Non-bacterial thrombotic endocarditis mitral valve
possible marker for pancreatic cancer
TNM staging
metastasis more important than nodal involvement
hepatocellular carcinoma, yolk sac tumors
prostate cancer
recurrence colorectal cancer
BJ (Bence-Jones) protein
multiple myeloma
β-human chorionic gonadotropin
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)
synthesized in peritubular capillaries
Reticulocyte count
measure of effective erythropoiesis; correct for degree of anemia
Extramedullary hematopoiesis
hematopoiesis outside bone marrow (e.g., spleen)
Newborn physiologic anemia
drop in Hb due to replacement of HbF RBCs with HbA
Hb and Hct decreased; greater increase in plasma volume than RBC mass
normal O2 saturation and arterial PO2
average volume of RBCs; useful for anemia classification
average Hb concentration in RBCs
↓ in microcytic anemias; ↑ in spherocytosis
↓ MCV, ↑ RBC count
RBC size variation; ↑ iron deficiency; normal in other microcytic anemias
Mature RBC
anaerobic glycolysis; no mitochondria or HLA antigens
Total iron binding capacity
↑ iron deficiency; ↓ anemia chronic disease, sideroblastic anemia
% Saturation
↓ iron deficiency, anemia chronic disease; ↑ sideroblastic anemia
Serum ferritin
↓ iron deficiency; ↑ anemia chronic disease, sideroblastic anemia; normal thalassemia
Microcytic anemias
iron deficiency MC, anemic chronic disease, thalassemia, sideroblastic anemia
Iron deficiency child
MCC Meckel's diverticulum
Iron deficiency woman < 50
MCC menorrhagia
Iron deficiency man < 50
MCC peptic ulcer disease
Iron deficiency men/woman > 50
MCC colon cancer
Stages iron deficiency
↓ ferritin; ↓ Fe and % saturation, ↑ TIBC; normocytic then microcytic anemia
Anemia chronic disease
MC anemia in malignancy and alcoholics
α-Thalassemia trait
AR; two α-globin gene deletions; normal Hb electrophoresis
HbH disease
three α-globin gene deletions; hemolytic anemia; four β-globin chains
Hb Bart's disease
four α-globin gene deletions; four γ-globin chains
β-Thalassemia minor
AR; DNA splicing defect; ↑ HbA2 and F; ↓ HbA
β-Thalassemia major
nonsense mutation with stop codon; hemolytic anemia; ↑↑ HbF, ↑ HbA2
Sideroblastic anemia
defect in mitochondrial heme synthesis producing ringed sideroblasts
Causes sideroblastic anemia
alcohol, pyridoxine deficiency (isoniazid Rx of TB), Pb poisoning
Pb poisoning
inhibition ferrochelatase, d-aminolevulinic acid dehydrase, ribonuclease
S/S Pb poisoning children
growth retardation; Pb in epiphyses (lead lines); abdominal colic; encephalopathy
S/S Pb poisoning adult
peripheral neuropathy; proximal renal tubule damage (Fanconi's syndrome)
Lab Pb poisoning
coarse basophilic stippling RBCs; ↓ MCV; ↑ blood Pb; ↑ d-aminolevulinic acid
Vitamin B12
animal products; requires intrinsic factor for reabsorption in terminal ileum
Vitamin B12
transfers methyl group to homocysteine
R factor
binds with B12 in mouth, removed by pancreatic enzymes in small intestine
Vitamin B12
involved in propionate metabolism; end-product succinyl CoA
Causes B12 deficiency
vegan, pernicious anemia MC, fish tapeworm, pancreatitis, bacterial overgrowth, Crohn's disease
Pernicious anemia
autoimmune destruction parietal cells; chronic gastritis body/fundus; achlorhydria; ↑ gastrin
Causes folate deficiency
alcohol MCC, poor diet, drugs, malabsorption, pregnancy, goat milk
Drugs and folate deficiency
alcohol, OC, phenytoin, methotrexate, trimethoprim, 5-fluorouracil
Intestinal conjugase in folate metabolism
inhibited by phenytoin
Jejunal uptake of monoglutamate form of folate
inhibited by alcohol and OC
Dihydrofolate reductase
inhibited by methotrexate, trimethoprim
Thymidylate synthetase
inhibited by 5-fluorouracil
Folate deficiency
MCC of increased serum homocysteine
Lab in B12/folate deficiency
pancytopenia; hypersegmented neutrophils; ↑ homocysteine
Lab findings unique to B12 deficiency
↑ gastrin (pernicious anemia), ↑ methylmalonic acid
B12 reabsorbed absorbed after administration of intrinsic factor
B12 reabsorbed absorbed after administration of antibiotics
bacterial overgrowth
B12 reabsorbed absorbed after administration of pancreatic extract
chronic pancreatitis
Acute blood loss
initially normal Hb and Hct; 0.9% saline uncovers RBC deficit
Aplastic anemia
drugs (e.g., phenylbutazone); infection (e.g., parvovirus); benzene
Lab findings aplastic anemia
pancytopenia; hypocellular bone marrow
Anemia in renal disease
normocytic; decreased EPO
Extravascular hemolysis
macrophage phagocytosis of RBCs; ↑ unconjugated bilirubin and urine UBG
Intravascular hemolysis
↓ serum haptoglobin; hemoglobinuria; hemosiderinuria
Congenital spherocytosis
AD; defect in spectrin; extravascular hemolysis; splenomegaly
Blood findings in spherocytosis
normocytic anemia; dense RBCs, ↑ MCHC, ↑ osmotic fragility
missing decay accelerating factor; complement destruction RBCs, neutrophils, platelets
pancytopenia; hemoglobinuria; positive sugar water test and acidified serum test
AR; missense mutation (valine for glutamic acid 6th positive β-globin chain)
Causes of sickling
↑ deoxyhemoglobin (hypoxemia, acidosis); HbS > 60%
inhibits sickling; hydroxyurea ↑ HbF
Pathophysiology HbSS
vasoocclusive crises, hemolytic anemia (extravascular)
HbSS children
dactylitis (6-9 months); Streptococcus pneumoniae sepsis (dysfunctional spleen)
HbSS osteomyelitis
Salmonella paratyphi
HbSS complications
aplastic crisis (parvovirus B-19), acute chest syndrome, autosplenectomy, calcium bilirubinate gallstones, priapism, aseptic necrosis
microhematuria from sickling in renal medulla; renal papillary necrosis
Hb electrophoresis
HbAS-HbA 55-60%, HbS 40-45%; HbSS-HbS 90-95%, HbF 5-10%
Blood findings in HbSS
sickle cells; target cells; Howell-Jolly bodies (nuclear remnants)
G6PD deficiency
XR; oxidant damage (peroxide) to Hb (e.g., primaquine; dapsone; fava beans)
Blood findings G6PD deficiency
Heinz bodies (denatured Hb; special stain); bite cells
Pyruvate kinase deficiency
↓ ATP; RBCs dehydrated; ↑ 2,3-BPG (right-shifted OBC)
Warm type AIHA
IgG; extravascular hemolysis; e.g., SLE, drugs
Cold type AIHA
IgM intravascular hemolysis; e.g., CLL, Mycoplasma
IgG antibody against penicillin attached to RBC (type II hypersensitivity)
drug alters Rh antigens; IgG antibody against Rh antigens (type II hypersensitivity)
drug-IgM IC; intravascular hemolysis; type III hypersensitivity
Lab findings AIHA
positive direct Coombs'; spherocytes
Micro-macroangiopathic hemolysis
mechanical damage causing intravascular hemolysis
Causes of micro/macro hemolysis
aortic stenosis (MCC), DIC, TIP, HUS
Peripheral blood findings micro/macro hemolysis
schistocytes; iron deficiency from hemoglobinuria
intravascular hemolysis correlates with fever; falciparum-ring forms and gametocytes
Leukemoid reaction
exaggerated WBC response to infection; usually due to infection
Leukoerythroblastic reaction
marrow infiltrative disease peripheralizes myeloblasts/nucleated RBCs
Causes of leukoerythroblastic reaction
bone metastasis MCC, myelofibrosis
type I hypersensitivity (e.g., penicillin reaction); invasive helminthic infection
Helminthes not producing eosinophilia
pinworms, adult worms in ascariasis
Atypical lymphocytes
mononucleosis; CMV; toxoplasmosis; viral hepatitis; phenytoin
due to EBV; EBV attaches to CD21 receptors on B cells
Clinical findings mono
exudative tonsillitis, generalized lymphadenopathy, hepatosplenomegaly
Lab findings mono
atypical lymphocytosis; IgM heterophile antibodies against horse RBCs
T cell deficiencies (HIV); combined B/T deficiency (adenine deaminase deficiency)
viral infections, whooping cough
lymphopenia, eosinopenia, neutrophilia
Chronic MPD
neoplastic stem cell disorder; splenomegaly; marrow fibrosis; risk for leukemia
Examples of MPD
polycythemia vera, myelofibrosis and myeloid metaplasia
Relative polycythemia
↓ plasma volume; ↑ RBC count; normal RBC mass
Absolute polycythemia
↓ RBC count and RBC mass
Appropriate polycythemia
hypoxic stimulus for EPO to generate RBCs
Causes of appropriate absolute polycythemia
lung disease, cyanotic heart disease, high altitude
Appropriate absolute polycythemia
normal plasma volume; ↑ RBC mass; ↓ SaO2; ↑ EPO
Inappropriate absolute polycythemia
no hypoxic stimulus for EPO
Causes of inappropriate polycythemia
ectopic secretion EPO, polycythemia vera
Polycythemia vera
↑ plasma volume and RBC mass; normal SaO2; ↓ EPO
Ectopic EPO (renal cell carcinoma)
normal plasma volume; ↑ RBC mass; normal SaO2; ↑ EPO
Myelofibrosis myeloid metaplasia
marrow fibrosis; extramedullary hematopoiesis; splenomegaly
Lab findings in myelofibrosis
tear drop RBCs; dry bone marrow aspirate (marrow fibrosis)
Essential thrombocythemia
MPO with increase in abnormal appearing platelets
Myelodysplastic syndrome
severe anemia in elderly; 30% develop leukemia; ringed sideroblasts
aplastic anemia; acute leukemia
Leukemia by age
ALL, newborn-14; AML, 15-60; CML, 40-60; CLL, >60
Acute vs. chronic leukemia
acute, blasts >30% in bone marrow; chronic, blasts <10% in bone marrow
Auer rods in myeloblasts
Acute promyelocytic leukemia
t(15;17); defect in retinoic acid; Rx retinoic acid (↑ maturation); DIC
Acute monocytic leukemia
gum infiltration
t(9;22) of ABL POC; Philadelphia chromosome 22; ↓ alkaline phosphatase score
early pre-B (80%); CALLA (CD10) and TdT positive; CNS and testicle involvement
t(12;21) offers good prognosis
B cell neoplasm; ↓ γ-globulins; MCC generalized lymphadenopathy patients> 60-yrs-old
Adult T cell leukemia
HTLV-1; CD4 T cells; skin infiltration; lytic bone lesions with hypercalcemia
Hairy cell leukemia
positive TRAP stain; splenomegaly; Rx with purine nucleosides
Nodal sites
germinal follicles, B cells; paracortex, T cells; sinuses, histiocytes
Testicular cancer
metastasizes to para-aortic nodes
Stomach cancer
metastasizes to left supraclavicular nodes (Virchow node)
atypical lymphocytosis
Cat scratch disease
Bartonella henselae; granulomatous microabscesses
Follicular B-cell lymphoma
t(14;18); overexpression of BCL-2 anti-apoptosis gene
Burkitt lymphoma
t(8;14); EBV association; common childhood NHL; "starry sky" appearance
Extra nodal lymphomas
risk factors H. pylori (stomach); Sjogren's syndrome
Mycosis fungoides
CD4 T cell neoplasm; skin lesions with Pautrier's microabscesses
Sezary syndrome
leukemic phase of mycosis fungoides
Polyclonal gammopathy
sign of chronic inflammation
Monoclonal gammopathy
M component (spike); sign of plasma cell disorder
Confirmatory tests
serum and urine immunoelectrophoresis; bone marrow aspirate
Bence Jones protein
light chains in urine; predictive of a malignant plasma cell disorder
Multiple myeloma
M spike; lytic bone lesions; pathologic fractures; hypercalcemia; renal failure
MC monoclonal gammopathy; may progress to myeloma
Findings in MGUS
elderly patient; no BJ protein; no malignant plasma cells
Waldenstrom's macroglobulinemia
lymphoplasmacytic lymphoma; IgM M spike; hyperviscosity
Hodgkin's lymphoma
neoplastic component, Reed Stemberg (RS) cell; CD15 CD30 positive
Lymphocyte predominant Hodgkin's
infrequent classic RS cells
Nodular sclerosing Hodgkin's
female dominant; supraclavicular nodes + anterior mediastinal nodes
Mixed cellularity Hodgkin's
male dominant; numerous RS cells; EBV association
Hodgkin's prognosis
stage of disease and type of Hodgkin's most important factors
Alkylating agents in Rx of Hodgkins
↑ risk for second malignancies (leukemia; NHL)
Langerhan's histiocytes
CD1 positive; Birbeck granules
Letterer-Siwe disease
malignant histiocytosis <2 yrs old; diffuse eczematous rash; organ involvement
Hand-Christian-Christian disease
malignant; lytic skull lesions, diabetes insipidus, exophthalmos
Eosinophilic granuloma
benign histiocytosis; lytic bone lesions with pathologic fractures
Mast cells
release histamine (pruritus; swelling); metachromatic granules positive with toluidine blue
Urticaria pigmentosum
localized mastocytosis; skin lesions swell and itch with scratching
twisted β-sheet; apple green birefringence with Congo red
Primary amyloidosis
AL amyloid derived from light chains; plasma cell disorders
Secondary amyloidosis
AA amyloid derived from serum-associated amyloid; chronic infections
Alzheimer's disease
amyloid precursor protein gene product chromosome 21; amyloid-β
Gaucher's disease
macrophages have fibrillary appearance; deficiency glucocerebrosidase
Niemann Pick's disease
macrophages have soap bubble appearance; deficiency sphingomyelinase
splenomegaly; peripheral blood cytopenias; portal hypertension MCC
Splenic dysfunction
Howell Jolly bodies; susceptible to Streptococcus pneumoniae sepsis
tissue plasminogen activator, heparin, PGI2 ATIII, protein C/S
enhances ATIII activity (neutralizes all factors except V, VIII, fibrinogen)
Protein C/S
neutralize V and VIII
coagulation factors, thromboxane A2 (platelet aggregation, vasoconstrictor)
Protein C and S
inactivate factors V and VIII; enhance fibrinolysis
von Willebrand factor
complexes with factor VIII to enhance VIII:C activity; platelet adhesion
receptors for von Willebrand factor and fibrinogen; synthesize thromboxane A2
platelet receptor for von Willebrand factor
platelet receptor for fibrinogen
Extrinsic system factor
Intrinsic system factors
Final common pathway factors
X, V, prothrombin (II), fibrinogen (I)
Factor XIII
cross-links insoluble fibrin; strengthens fibrin clots
Vitamin K-dependent factors
prothrombin, VII, IX, X, protein C and S
Factors consumed in a clot
fibrinogen, prothrombin, V, VIII; fluid is called serum
cleaves fibrinogen and insoluble fibrin into degradation products
Bleeding time
evaluates platelet function (adhesion, release reaction, aggregation)
MCC of a prolonged bleeding time
Tests for vWF
ristocetin cofactor assay; vWF antigen assay; agar electrophoresis
evaluates extrinsic pathway to fibrin clot
evaluates intrinsic pathway to stable fibrin clot
Fibrinolysis tests
fibrin(ogen) degradation products; D-dimers (cross-linked insoluble fibrin)
S/S platelet dysfunction
cannot form temporary plug; epistaxis; petechiae; bleeding from scratches
Idiopathic thrombocytopenic purpura (ITP)
children; antibodies against GpIIb:IIIa; no splenomegaly
Chronic autoimmune thrombocytopenic purpura
SLE; antibodies against GpIIb:IIIa receptors
thrombocytopenia due to IgG antibody against heparin attached to PF4 on platelets
heparin neutralizing factor
thrombocytopenia MC hematologic abnormality; similar to ITP
platelet thrombi develop in areas of endothelial damage in small vessels; consumption of platelets
fever, thrombocytopenia, renal failure, hemolytic anemia with schistocytes, CNS deficits
Lab findings TTP
thrombocytopenia, prolonged bleeding time, normal PT and PTT
similar to TTP; endothelial injury from Shiga-like toxin of 0157:H7 E. coli in undercooked beef
S/S factor deficiency
no stable fibrin clot-late rebleeding; menorrhagia; GI bleeding; hemarthroses
Hemophilia A
XR; hemarthroses; prolonged PTT, ↓ factor VIII activity, normal VIII antigen
von Willebrand's disease
AD; platelet adhesion defect + factor VIII deficiency
Lab findings in VWD
↓ vWF, VIII antigen, and VIII:C; prolonged bleeding time
Desmopressin acetate
Rx of choice for mild von Willebrand's disease and hemophilia A
Circulating anticoagulants
antibodies destroy coagulation factors
Lab finding in circulating anticoagulant
prolonged PT and/or PTT corrected with mixing studies
Vitamin K deficiency
↓ epoxide reductase activity (↓ function vitamin K); hemorrhagic diathesis; ↑ PT
Causes vitamin K deficiency
antibiotics MC, newborn, malabsorption, warfarin
activation coagulation system from release of tissue thromboplastin and/or endothelial cell damage
consumption coagulation factors by fibrin clots; patient also anticoagulated
septic shock MCC, rattlesnake bite, massive trauma, amniotic fluid
bleeding from all scratches, holes, needle sites
Lab findings DIC
thrombocytopenia, ↑ PT and PTT, D-dimers (best test), anemia
Antiphospholipid antibodies
lupus anticoagulant and anticardiolipin antibodies; vessel thrombosis
inhibits epoxide reductase; PT best test but PTT also prolonged
full anticoagulation in 3 days when -carboxylated prothrombin disappears
ingredient in rat poison; danger to children in households with grandparents on warfarin
Rx warfarin over anticoagulation
intramuscular vitamin K (6-8 hrs), fresh frozen plasma (immediate)
enhances ATIII; PTT best test but PT also prolonged
estrogen ↑ coagulation factor synthesis and ATIII; predisposes to thrombosis
Factor V Leiden
MC hereditary thrombosis; resistant to degradation by protein C/S
ATIII deficiency
no prolongation of PTT with administration of heparin
Hemorrhagic skin necrosis
post-warfarin therapy in patient with heterozygote protein C deficiency
M cells
specialized cells that transfer foreign antigens to lymphocytes in Peyer's patches
Blood group O
some patients have anti-AB-IgG antibodies; increased incidence duodenal ulcers
Blood group A
increased incidence of gastric carcinoma
do not have natural blood group antibodies at birth (e.g., anti-A-lgM)
may lose natural blood group antibodies; no hemolytic reaction to mismatched blood
Rh antigens
inherited in autosomal codominant fashion; Rh antigens include D, C, c, E, e
Atypical antibodies
antibodies against Rh or non-Rh blood group antigens (e.g., anti-D)
Duffy antigen
receptor for Plasmodium vivax; blacks often lack Duffy antigen
Antibody screen
indirect Coomb's test; detects atypical antibodies in serum
MC infection transmitted by blood transfusion; MC antibody
Hepatitis C
MCC of post-transfusion hepatitis
Major crossmatch
patient serum reacted against donor RBCs; does not guarantee RBC survival
Universal donor
blood group O; no antigens on the surface of RBCs
Universal recipient
blood group AB; no natural blood group antibodies in serum
Packed RBC transfusion
raises Hb by 1 gm/dL and Hct by 3%
fibrinogen and factor VIII
Fresh frozen plasma
replacement for multiple factor deficiencies (e.g., cirrhosis, DIC)
Allergic transfusion reaction
type I IgE-mediated hypersensitivity reaction
Febrile transfusion reaction
recipient anti-HLA antibodies react against donor leukocytes
Intravascular HTR
transfusion of ABO incompatible blood (e.g., A person receives B blood)
Extravascular HTR
antibody attaches to donor RBCs; macrophage phagocytosis and hemolysis
Positive direct Coomb's test
present in both types of hemolytic transfusion reactions
jaundice, no increase in Hb, hemoglobinuria
mother O and baby A or B; transplacental passage of maternal anti-AB-IgG
positive direct Coomb's test; spherocytes; MCC unconjugated hyperbilirubinemia first 24 hrs
mother Rh (D antigen) negative and fetus Rh (O antigen) positive
no hemolysis in first Rh incompatible pregnancy
maternal anti-D crosses placenta; potential for hydrops fetalis; high risk for kernicterus
Rh immune globulin
anti-D; coats D antigen site on fetal RBCs in maternal circulation
Rh HDN lab
positive direct Coomb's; severe anemia and hyperbilirubinemia
protects mother from Rh sensitization (development of anti-D antibodies)
O Rh negative mother with A Rh positive baby
A+ cells destroyed by mothers anti A-lgM
Blue fluorescent light
converts unconjugated bilirubin in skin into harmless water soluble dipyrrole
MV auscultation
TV auscultation
left parasternal border
AV auscultation
right 2nd intercostal space
PV auscultation
left 2nd intercostal space
closure MV and TV
closure AV and PV
split in A2 and P2; due to increased blood in right side of heart
abnormal; due to blood entering volume overloaded ventricle in early diastole
Causes S3
valve regurgitation; congestive heart failure
abnormal; due to blood entering non-compliant ventricle with atrial contraction in late diastole
Causes S4
volume overloaded ventricle, hypertrophy
stretching valve ring or damage to valve
increases right sided abnormal heart sounds and murmurs
increases left sided abnormal heart sounds and murmurs
Stenosis murmurs
problem in opening valve
Regurgitation murmurs
problem in closing valve
Valves opening in systole
AV and PV
Valves opening in diastole
MV and TV
Valves closing in systole
MV and TV
Valves closing in diastole
AV and PV
primary vehicle for carrying cholesterol
primary vehicle for carrying liver-synthesized triglyceride
Familial hypercholesterolemia (type II)
AD; deficiency of LDL receptors; ↑ LDL
Type III hyperlipoproteinemia
deficiency apo E; ↑ remnants (chylomicron, intermediate density)
Type IV hyperlipoproteinemia
↑ VLDL; alcoholics
Apo B deficiency
deficiency apo B48 (chylomicrons) and B100 (VLDL); ↓ CH and TG
Clinical findings in apo B deficiency
malabsorption; hemolytic anemia
reaction to injury of endothelial cells
Risk factors
smoking, ↑ LDL, ↑ homocysteine, Chlamydia pneumoniae infection
Cells involved
platelets, macrophages, smooth muscle cells, T cells with cytokine release
Fibrous plaque
pathognomonic lesion of atherosclerosis
C-reactive protein
marker of an inflammatory atheromatous plaque
Inflammatory atheromatous plaque
predisposes to platelet thrombosis
Increased plasma homocysteine
↑ vessel thrombosis; folate (MC)/vitamin B12 deficiency
Hyaline arteriolosclerosis
small vessel disease of DM and hypertension; excess protein in vessel wall
Mechanisms hyaline arteriolosclerosis in DM
non-enzymatic glycosylation
Non-enzymatic glycosylation
glucose attaches to amino acids in BM; causes ↑ permeability to protein
Mechanisms hyaline arteriolosclerosis in hypertension
pressure pushes proteins into vessel wall
Abdominal aortic aneurysm rupture
due to atherosclerosis; flank pain, hypotension, pulsatile mass
Syphilitic aneurysm
vasculitis of vasa vasorum of aortic arch; aortic regurgitation
Aortic dissection
due to hypertension and collagen tissue disorders (e.g., Marfan)
Cystic medial degeneration
elastic tissue degeneration creates spaces filled with mucopolysaccharides
Intimal tear in aorta
due to wall stress from hypertension and structural weakness
Types of dissection
proximal (MC); distal or combination of both
S/S proximal aortic dissection
chest pain radiating to back, lack of pulse; cardiac tamponade MC COD
AD; fibrillin defect; aortic regurgitation/dissection; lens dislocation; MVP with sudden death
MC COD Marfan's and Ehlers Danlos
aortic dissection
stasis of blood flow; deep veins below knee MC site
Pulmonary thromboembolism
emboli originate from femoral veins
Superficial migratory thrombophlebitis
sign of carcinoma of head of pancreas
Thoracic outlet syndrome
absent radial pulse with positional change
Turner's syndrome
lymphedema hands/feet in newborn; preductal coarctation
Spider telangiectasia
arteriovenous fistula; due to hyperestrinism (cirrhosis, pregnancy)
Capillary hemangioma in newborn
regress with age; do not surgically remove
Kaposi's sarcoma
HHV-8; vascular malignancy; MC cancer in AIDS
Bacillary angiomatosis
Bartonella henselae; vascular infection in AIDS
Small vessel vasculitis
palpable purpura; e.g., Henoch Schonlein purpura
Muscular artery vasculitis
vessel thrombosis with infarction; e.g., classical polyarteritis nodosa
Elastic artery vasculitis
absent pulse, stroke
Takayasu's arteritis
pulseless disease; young Asian woman
Giant cell arteritis
temporal artery granulomatous vasculitis; ipsilateral blindness (ophthalmic artery)
Classical polyarteritis nodosa
muscular artery vasculitis with vessel thrombosis infarction
Path findings
vessel inflammation at different stages; aneurysms from vessel weakness
infarctions in kidneys, skin, GI tract, heart; HBsAg in 30%
angiography identifies aneurysms and thrombosis
Kawasaki's disease
coronary artery vasculitis/thrombosis/aneurysms in children
chest pain; desquamating rash; swelling hands/feet; cervical lymphadenopathy
IV γ-globulin
Buerger's disease (thromboangiitis obliterans)
smoker's digital vasculitis; digital infarction
Raynaud's syndrome
digital vasculitis in PSS and CREST syndrome
digital pain; white-blue-red color changes
protein gels in cold temperature; Raynaud's syndrome; HCV association
acral cyanosis relieved by coming indoors
Wegener's granulomatosis
association with c-ANCA; sinusitis, lung infarction, crescentic GN
Microscopic polyangiitis
palpable purpura; crescentic GN; association with p-ANCA
Henoch-Schönlein purpura
IgA-anti-IgA ICs; palpable purpura buttocks/legs; arthritis; IgA GN
Serum sickness vasculitis
e.g., horse antivenin in Rx of rattlesnake envenomation
Rocky Mountain spotted fever
tick borne
sepsis causes petechia/ecchymoses; potential for Waterhouse Friderichsen syndrome
Essential HTN blacks
defect in renal excretion of sodium; ↑ plasma volume, ↓ PRA
Renovascular HTN
atherosclerosis renal artery in men; fibromuscular hyperplasia renal artery women
epigastric bruit; ↑ PRA affected kidney, ↓ PRA unaffected kidney
Endocrine HTN
1º HPTH, Graves/hypothyroidism, Cushing's, 1º aldosteronism, phaeochromocytoma
LVH MC complication; AMI MC COD followed by stroke and renal failure
resistance ventricles contract against
volume ventricles must eject
Concentric LVH
increased afterload; e.g., essential HTN, aortic stenosis
LVH with dilation/hypertrophy
increased preload; e.g., valve regurgitation; left to right shunts
forward failure; pulmonary edema, pillow orthopnea, paroxysmal nocturnal dyspnea
Systolic dysfunction
LHF due to decreased ventricular contractility (ischemia)
Diastolic dysfunction
LHF due to decreased ventricular compliance (hypertrophy)
backward failure; ↑ venous hydrostatic pressure; neck vein distention, hepatomegaly, edema
ACE inhibitors
decrease afterload and preload in heart failure
Diuretics in CHF
reduce preload
Non-pharmacologic Rx in CHF
restrict salt and water
MC COD in United States; left anterior descending coronary artery thrombosis MCC
Exertional angina
coronary artery atherosclerosis; subendocardial ischemia; ST depression
Prinzmetal's angina
coronary artery vasospasm; transmural ischemia; ST elevation
Sudden cardiac death
death within 1 hr of symptoms
Path findings
severe coronary artery atherosclerosis; absence of occlusive thrombosis
LAD coronary artery
anterior portion left ventricle, anterior 2/3rds IVS
posterior portion left ventricle and papillary muscle, inferior 1/3rd IVS, right ventricle
rupture of inflammatory plaque produces platelet thrombus
Ventricular fibrillation
no gross changes until 24 hrs
retrosternal pain radiating down arms, diaphoresis
AMI ruptures
3rd-7th day
Anterior wall rupture
MC type; LAD thrombosis; cardiac tamponade
Posteromedial papillary muscle rupture
RCA thrombosis; mitral regurgitation with LHF
IVS rupture
LAD thrombosis; left to right shunt; RHF
Mural thrombus
anterior AMI; danger embolization
first week in transmural AMI; 6 wks later autoimmune
friction rub; leaning forward relieves pain
Ventricular aneurysms
late manifestation of AMI; precordial systolic bulge; CHF MC COD
Right ventricular infarction
RCA thrombosis; hypotension, RHF, preserved left ventricular function
Diagnosis of AMI
CK-MB and troponins; CK-MB absent by 3 days; troponins last 7-10 days
LDH isoenzymes
no longer used; LDH 1/2 flip indicates AMI
reappearance CK-MB after 3 days
ECG findings in AMI
inverted T waves; ST elevation; Q waves
Ejection fraction
EF = stroke volume/left ventricular end-diastolic volume; 80/120 = 0.66
By-pass surgery
use internal mammary artery and saphenous veins ("arterialize" after 10 yrs)
Angioplasty complication
localized dissection with thrombosis
Umbilical vein
highest O2 saturation
Ductus arteriosis in fetus
shunts blood from pulmonary artery to aorta; PGE keeps it open
Ductus arteriosus in newborn
closes and becomes ligamentum arteriosum
Eisenmenger's syndrome
cyanosis due to reversal of left to right shunt
MC congenital heart disease; ↑ SaO2 right ventricle (RV), pulmonary artery (PA)
patent foramen ovale; ↑ SaO2 right atrium (RA), RV, PA; MC adult congenital heart disease
Down syndrome
endocardial cushion defect (combined ASD and VSD)
machinery murmur; close with indomethacin; ↑ SaO2 PA
Tetralogy of Fallot
degree of pulmonic stenosis determines if cyanosis is present
Tetralogy of Fallot
↓ left ventricle, aorta
Tetralogy of Fallot
ASD and PDA are cardioprotective
Complete transposition
cyanosis; aorta empties RV; PA empties left ventricle
Complications cyanotic heart disease
2° polycythemia; infective endocarditis; metastatic abscesses
Pre-ductal coarctation
Turner's syndrome
Post-ductal coarctation
constriction distal to ligamentum arteriosum
upper extremity HTN; claudication; rib-notching; activation RAA also causes HTN
Acute rheumatic fever
type II hypersensitivity; group A streptococcus pharyngeal infection
Acute rheumatic fever
sterile vegetations mitral valve (regurgitation); myocarditis with Aschoff nodule
polyarthritis (MC), carditis, erythema marginatum, rheumatoid nodules, chorea
Mitral stenosis
chronic rheumatic fever; opening snap followed by mid-diastolic rumble
Mitral stenosis
left atrial dilation hypertrophy - atrial fibrillation, thrombus, pulmonary edema, RHF
myxomatous degeneration of mitral valve; common in Marfan syndrome, Ehlers Danlos
mid-systolic click followed by a murmur; palpitations, chest pain, rupture of chordae
MVP click/murmur close to S1
decrease preload (stand, Valsalva, anxiety)
MVP click/murmur close to S2
increase preload (supine, squat, clench fist)
Mitral regurgitation
pansystolic murmur; S3 and S4 common
LHF, infective endocarditis, acute rheumatic fever
Aortic stenosis
systolic ejection murmur; syncope and angina with exercise; hemolytic anemia
Aortic stenosis murmur increased preload
worsens obstruction and increases murmur intensity
Aortic stenosis murmur decreased preload
decreases obstruction and decreases murmur intensity
bicuspid aortic valve; age-related sclerosis
Aortic regurgitation
bounding pulses; early diastolic blowing murmur
Austin Flint murmur
diastolic murmur; regurgitant flow on anterior leaflet mitral valve
Significance Austin Flint murmur
sign for AV replacement
Causes aortic regurgitation
essential HTN, infective endocarditis, acute rheumatic fever, dissection
Tricuspid regurgitation
pansystolic murmur ↑ intensity with inspiration
endocarditis IV drug abuse; RHF; carcinoid heart disease
Carcinoid heart disease
tricuspid regurgitation, pulmonic stenosis
Infective endocarditis (IE)
Streptococcus viridans MCC; Staphylococcus aureus MCC IVDA
IE prosthetic heart valve
Staphylococcus epidermidis (coagulase negative)
IE ulcerative bowel disease
Streptococcus bovis
IC vasculitis-Roth spot, splinter hemorrhages; regurgitant murmurs; metas1atic abscesses
Lab findings
positive blood culture Libman Sacks endocarditis
MCC of myocarditis (lymphocyte infiltrate in myocardium) and pericarditis
Parasitic cause myocarditis
leishmania in Chagas disease
Pericardial effusion
all chamber pressures are uniformally increased
muffled heart sounds, pulsus paradoxus, inspiratory neck vein distention
Dx and Rx
echocardiogram, pericardiocentesis, respectively
Pulsus paradoxus
drop in blood pressure >10 mmHg with inspiration
Constrictive pericarditis
TB MCC worldwide; pericardial knock
Congestive cardiomyopathy
generalized chamber enlargement; low ejection fraction
postpartum, cardiotoxic drugs, hypothyroidism, alcohol
Hypertrophic cardiomyopathy
MCC of sudden death in young person (due to conduction defects)
Site of obstruction
anterior leaflet mitral valve drawn against asymmetric thickened IVS
Effect decreased preload on systolic murmur
worsens obstruction and increases murmur intensity
Effect increased preload on systolic murmur
reduces obstruction and decreases murmur intensity
Restrictive cardiomyopathy
decreased compliance
iron, amyloid, glycogen; sarcoidosis; tropical endocardial fibrosis
Cardiac myxoma
benign tumor left atrium; embolization; syncope
Cardiac rhabdomyoma
childhood tumor; association with tuberous sclerosis
U wave
hypokalemia; MCC diuretic therapy (e.g., thiazides; loop diuretics)
Peaked T wave
hyperkalemia; MCC renal failure
ST depression
subendocardial ischemia (e.g., classical angina pectoris)
ST elevation
transmural ischemia (e.g., AMI), pericarditis, ventricular aneurysm
Atrial fibrillation
MC chronic arrhythmia; absent P waves; danger for embolization
Ventricular premature beats
wide QRS complexes; MC arrhythmia in coronary care unit
Ventricular fibrillation
MCC of death in an AMI
Anterior AMI
Q waves in I and V1-V4
Inferior AMI
Q waves in II, III, and aVF; right coronary artery thrombosis.
short PR interval with normal P wave; delta wave on upstroke of R wave
Alveolar O2 calculation
% O2 breathing (713) - PCO2/0.8
Increased A-a gradient
primary lung disease; left to right shunts in heart
Forced vital capacity
total amount of air expelled after a maximal inspiration
Forced expiratory volume/1 second (FEV1)
amount of air expelled in I second after maximal inspiration
Choanal atresia
cyanotic when breast feeding; turns pink when crying
Nasal polyps
allergic (MC; adults only), aspirin, cystic fibrosis
Nasal polyp in a child
requires sweat test to exclude cystic fibrosis
Triad asthma
patient on aspirin (pain syndrome) with nasal polyps, asthma
Obstructive sleep apnea (OSA)
snoring with intervals of apnea (respiratory acidosis with hypoxemia)
danger cor pulmonale; requires sleep test; Rx. O2 with continuous positive airway pressure
maxillary sinusitis MC in adults; ethmoiditis MC in children; S. pneumoniae MC
Nasopharyngeal carcinoma
association with EBV; metastasize to cervical nodes
Laryngeal carcinoma
smoking MCC; hoarseness; squamous cell carcinoma
Resorption atelectasis
MCC of fever 24-36 hours after surgery
↓ percussion; absent fremitus, breath sounds; inspiratory lag; elevated diaphragm
decreased production surfactant; airway collapse; hyaline membranes
Type II pneumocytes
synthesize surfactant (lecithin, phosphatidylcholine); stored in lamellar bodies
reduces surface tension in airways; ↑ synthesis cortisol, thyroxine; ↓ synthesis insulin
Causes RDS
prematurity, maternal diabetes, C-section
Maternal diabetes
maternal hyperglycemia → fetal hyperglycemia → fetal insulin which ↓ surfactant
Complications RDS
O2 FR injury (blindness, bronchopulmonary dysplasia); necrotizing enterocolitis
Typical community acquired pneumonia
Streptococcus pneumoniae MCC
Typical pneumonia
bronchopneumonia, lobar pneumonia
productive cough; consolidation - ↓ percussion, ↑ tactile fremitus
Atypical community acquired pneumonia
interstitial pneumonia; Mycoplasma pneumoniae MCC
low grade fever, non-productive cough, no signs consolidation
Nosocomial pneumonia
Pseudomonas, aeruginosa MCC (respirators); others - S. aureus, E. coli
MCC common cold; hand to mouth transmission
Respiratory syncytial virus
MCC pneumonia and bronchiolitis in child
Parainfluenza virus
MCC croup in child; trachea area of obstruction
basophilic intranuclear inclusion surrounded by halo
superimposed pneumonia with S. aureus increases mortality
Warthin-Finkeldey multinucleated giant cells
Chlamydia pneumoniae
atypical pneumonia; association with coronary artery disease
Chlamydia trachomatis
pneumonia in newborns; staccato cough; wheezing
Coxiella burnetii
only rickettsia without a vector
Mycoplasma pneumoniae pneumonia
crowded condition; cold agglutinins; azithromycin
Streptococcus pneumoniae pneumonia
gram positive diplococcus; azithromycin
Staphylococcus aureus pneumonia
tension pneumatocysts in children with cystic fibrosis
Corynebacterium diphtheriae
toxin produces ADP ribosylation of elongation factor 2
Haemophilus influenzae
exacerbation chronic bronchitis; acute epiglottis in children
Inspiratory stridor child
croup, epiglottitis
Pseudomonas aeruginosa
MCC of pneumonia and death in cystic fibrosis; green sputum
Klebsiella pneumoniae
mucoid sputum in alcoholic
Legionella pneumophila
silver stain; water coolers/mist (grocery produce, restaurants, zoo rain forest)
Mycobacterium tuberculosis
strict aerobe; MC COD due to infectious disease worldwide
Candida albicans
vessel invader; yeasts and pseudohyphae
Cryptococcus immitis
pigeon excreta; narrow-based bud
Aspergillus fumigatus
septate hyphae with fruiting body; fungus ball, extrinsic asthma, vessel invader
Mucor species
non-septate; vessel invader; frontal lobe abscess in diabetic ketoacidosis
Coccidioides immitis
Southwest deserts; inhale arthrospores in dust; spherule with endospores
erythema nodosum (painful nodules lower legs)
Histoplasma capsulatum
Ohio/central Mississippi river valley; excreta bats (spelunker), chickens
H. capsulatum
simulates TB; yeasts phagocytosed by macrophages
Blastomyces dermatitidis
overlaps histoplasmosis; broad-based buds; skin lesion simulates cancer
Pneumocystis carinii
cysts and trophozoites; pneumonia in HIV; Rx. trimethoprim/sulfamethoxazole
Primary TB
upper portion lower lobe, lower portion upper lobe
Primary TB
Ghon focus (subpleural caseation); Ghon complex (spread to hilar nodes)
Reactivation TB
cavitating lesion in upper lobe; kidney MC extrapulmonary site
Mycobacterium avium intracellulare (MAI)
atypical TB; MC TB in AIDS
AR; 3 nucleotide deletion chromosome 7; defective CFTR (degraded in Golgi apparatus)
pneumonia, malabsorption, males sterile; + sweat test; P. aeruginosa pneumonia MC COD
Lung abscess
MCC aspiration oropharyngeal material (mixed aerobe/anaerobe); x-ray - air/fluid level
Aspiration sitting
posterobasal segment right lower lobe
Aspiration supine
superior segment right lower lobe
Aspiration right side
right middle lobe, posterior segment right upper lobe
Pulmonary thromboembolism
most derive from femoral vein
Bronchial artery
branch of aorta/intercostal artery; protects against developing pulmonary infarction
Saddle embolus
sudden death due to acute right heart strain
S/S pulmonary infarction
dyspnea and tachypnea; pleuritic chest pain; pleural effusion
ventilation/perfusion scan; respiratory alkalosis; hypoxemia
Pain on inspiration
pleuritic inflammation; pulmonary embolus, pneumonia, pneumothorax
Pathogenesis pulmonary hypertension (PH)
hypoxemia and respiratory acidosis
Hypoxemia + respiratory acidosis
vasoconstriction pulmonary vessels; vasodilation cerebral vessels
Causes PH
1° lung disease (COPD, restrictive), recurrent emboli, mitral stenosis, OSA, left-right shunts
Cor pulmonale
dyspnea; accentuated P2 (PH); parasternal heave (RVH)
Restrictive lung disease
↓ compliance, ↑ elasticity; interstitial fibrosis/edema
Restrictive lung disease (RLD)
↓ all volumes and capacities; ↑ FEV1sec/FVC ratio
RLD; non-cardiogenic pulmonary edema due to alveolar injury
neutrophil destruction of type I and II pneumocytes; hyaline membranes
septic shock (MC), aspiration gastric contents, severe trauma
inhalation mineral dust causing interstitial fibrosis; particles <0.5 μm to reach alveoli
Caplan syndrome
pneumoconiosis + rheumatoid nodules in lungs
Coal worker's
"black lung" disease; progressive massive fibrosis; no increased incidence cancer or TB
quartz; nodular opacities; foundry workers; ↑ incidence cancer and TB
Sources asbestos
roofing material, old buildings (9/11), pipe-fitter shipyard
Ferruginous bodies
asbestos fiber coated by iron
benign pleural plaques (MC); bronchogenic carcinoma (MC cancer); mesothelioma
malignancy of serosa; no smoking association
RLD; MC non-infectious lung and liver granulomatous disease
dyspnea, hilar adenopathy (non-caseating granulomas), uveitis, nodular skin lesions
Lab findings
↑ ACE, hypercalcemia (macrophages synthesize 1-α-hydroxylase)
Kveim test
intradermal injection sarcoid antigens causes skin reaction
Farmer's lung
RLD; lung reaction against thermophilic bacteria in moldy hay
Silo filler's disease
RLD; reaction against nitrogen dioxide in fermenting corn
RLD; reaction against cotton, linen, hemp products in textile industry
Goodpasture's syndrome
RLD; anti-BM antibodies; begins in lungs and ends in renal failure
Collagen vascular RLD
SLE, rheumatoid arthritis, systemic sclerosis
Drugs RLD
amiodarone, bleomycin, busulfan, cyclophosphamide, methotrexate, nitrofurantoin
Obstructive lung disease
↑ compliance, ↓ elasticity
Obstructive lung disease
↑ RV, TLC; ↓ TV, VC; ↓ FEV1sec and FVC; ↓ FEV1sec/FVC ratio
Obstructive lung disease
asthma, emphysema, chronic bronchitis, bronchiectasis
extrinsic (type I hypersensitivity) and intrinsic types
expiratory wheezing (inflamed terminal bronchioles); LTC4,-D4,-E4 bronchoconstrictors
Charcot-Leyden crystals
derive from crystalline material in eosinophil granules
Lab findings
initial respiratory alkalosis; respiratory acidosis requires intubation
destruction elastic tissue respiratory unit; lung hyperinflation; smoking MCC; pink puffer
Respiratory unit
respiratory bronchiole, alveolar duct, alveoli
Radiograph emphysema
↑ AP diameter; depressed diaphragms; vertical heart
↓ AAT, ↑ neutrophil destruction of elastic tissue
Centriacinar emphysema
destruction/distention respiratory bronchioles upper lobe in smokers; THINK
Panacinar emphysema
destruction/distention entire respiratory unit lower lobes; AAT deficiency
Paraseptal emphysema
upper lobe destruction/distention alveolar ducts, alveoli; pneumothorax
Lab findings
normal to decreased PCO2 (respiratory alkalosis)
Chronic bronchitis
productive cough 3 months/2 consecutive years; blue bloater (cyanosis)
Site of obstruction
terminal bronchioles (proximal to respiratory unit)
Lab findings
respiratory acidosis/hypoxemia
obstruction/infection key causes; dilated bronchioles extend to periphery
CF MCC, TB, immotile cilia syndrome
Immotile cilia syndrome
absent dynein arm in cilia; sinusitis, infertility, bronchiectasis, situs inversus
Central lung cancers
squamous cancer and small cell cancer; men > women
Peripheral lung cancers
adenocarcinoma; women > men
Squamous lung cancer
cavitate; secrete PTH-related protein
Small cell carcinoma
neuroendocrine tumor; secrete ACTH and ADH
Bronchioloalveolar carcinoma
no smoking relationship; lung consolidation resembling pneumonia
Scar carcinoma
usually adenocarcinoma developing in old TB scar
Bronchial carcinoid
low grade malignant; hemoptysis; rare cause carcinoid syndrome
Metastatic lung cancer
more common than primary cancer; breast cancer MCC
Pancoast tumor
squamous carcinoma posterior mediastinum; destruction superior cervical ganglion
Horner's syndrome - lid lag, miosis, anhydrosis; lower brachial plexus injury
Solitary coin lesion
granuloma MCC
Superior vena caval syndrome
primary lung cancer obstructs vessel; venous congestion
Anterior mediastinal masses
thymoma; nodular sclerosing Hodgkin's; teratomas
Posterior mediastinal masses
usually neurogenic tumors of ganglia
Myasthenia gravis
B cell hyperplasia of thymus MC abnormality; association with thymoma
association with hypogammaglobulinemia, autoimmune disease, pure RBC aplasia
Pleural effusions
transudates or exudates; CHF MCC
Spontaneous pneumothorax
rupture subpleural or intrapleural bleb; air/pleural cavity pressure same
pleuritic chest pain, dyspnea, tracheal shift ipsilateral side, absent breath sounds
Tension pneumothorax
flap-like pleural tear; increased pleural cavity pressure; compression atelectasis
as above except tracheal shift to opposite side
Cleft lip/palate
failure of fusion of facial processes
Herpes labialis
multinucleated giant cell with acidophilic intranuclear inclusions on Tzanck prep
Hairy leukoplakia
EBV glossitis; pre-AIDS defining lesion; not precursor to cancer
bilateral parotitis; unilateral orchitis; ↑ amylase
pseudomembrane pharynx and trachea with cervical lymphadenopathy
Congenital syphilis
notched central incisors
anaerobic gram + filamentous bacteria; complication extracted dental abscess
draining sinuses with sulfur granules
Exudative tonsillitis
majority are viral; 20% group A streptococcus
Oral thrush
common in newborn; pre-AIDS defining lesion; yeasts and pseudohyphae
Dental caries
Streptococcus mutans
Peutz-Jegher's syndrome
mucosal pigmentation; hamartomatous polyps
biopsy to rule out squamous dysplasia or cancer
Squamous cell carcinoma
smoking and alcohol association; lower lip MC site
Smokeless tobacco
verrucoid squamous cell carcinoma
Gum hyperplasia
phenytoin, pregnancy, scurvy
Pleomorphic adenoma
MC benign tumor of salivary glands; parotid MC site
Mucoepidermoid carcinoma
MC malignant tumor major and minor salivary glands
Dysphagia for solids only
lesion obstructing esophagus; e.g., cancer, web
Plummer-Vinson syndrome
iron deficiency anemia causes esophageal web, glossitis, achlorhydria (↓ HCl in gastric acid)
Dysphagia for solids and liquids
motor abnormality; e.g., achalasia MCC, PSS or CREST syndrome
TE fistula
polyhydramnios; proximal esophagus ends blindly; distal esophagus derives from trachea
VATER syndrome
vertebral abnormalities, anal atresia, TE fistula, renal disease/radius abnormality
Zenker's diverticulum
MC pulsion diverticulum of esophagus; halitosis (stinky breath, food gets stuck); near UES
relaxation of lower esophageal sphincter (LES) with acid reflux
MCC nocturnal cough and asthma
AIDS esophagitis
Candida MC, CMV, HSV
Barrett's esophagus
glandular metaplasia distal esophagus in GERD
Complications of Barrett's
precursor for adenocarcinoma, stricture
Esophageal varices
dilated left gastric vein; sign of portal hypertension due to cirrhosis
Mallory Weiss syndrome
tear of distal esophagus from retching in alcoholic or bulimic
Boerhaave's syndrome
rupture of distal esophagus from retching; pneumomediastinum
Hamman's mediastinal crunch
pneumomediastinum (air in subcutaneous tissue)
LES ganglion cells
contain VIP - relaxes LES
failure of LES relaxation (no VIP); absent ganglion cells in the myenteric plexus
aperistalsis/dilation of esophagus; regurgitation of undigested food at night
X-ray achalasia
bird's beak appearance
Acquired achalasia
Chagas' disease; leishmania destroy ganglion cells
Distal adenocarcinoma esophagus
MC primary cancer; due to Barrett's esophagus
Squamous cell carcinoma of esophagus
smoking MCC; alcohol also causes
sign of upper GI bleed; acid changes Hb to hematin; peptic ulcer disease MCC
vomiting blood; peptic ulcers MCC
Congenital pyloric stenosis
hypertrophy pyloric muscle; vomiting non-bile stained fluid in 2-4 weeks
Acute hemorrhagic (erosive) gastritis
Mucous barrier stomach
maintained by PGE; misoprostol PGE analog
Type A chronic gastritis
due to PA; achlorhydria with ↑ serum gastrin
Type B chronic gastritis
due to H. pylori; involves pylorus and antrum
H. pylori
curved rod; urease producer; MCC PUD, adenocarcinoma, gastric lymphoma
Gastric ulcer
lesser curvature pylorus and antrum; poor defense against acid; food aggravates pain
Duodenal ulcer
never malignant; ↑ acid production; food relieves pain
Perforated peptic ulcer
air under diaphragm causes pain in left shoulder
Menetrier's disease
giant rugal hyperplasia; protein loss from increased mucus
Zollinger-Ellison syndrome
malignant islet cell tumor secreting gastrin; part of MEN I syndrome
PUD in usual locations; sometimes multiple ulcers
ZE, achlorhydria, gastric distention, H2 or proton blockers; renal failure
MC benign tumor of stomach
Intestinal type adenocarcinoma
H pylori related; ↓ incidence; lesser curvature pylorus/antrum
Diffuse type adenocarcinoma
linitis plastica; signet ring cells; Krukenberg tumors ovaries
Gastric lymphoma
stomach MC site for extranodal lymphomas; H. pylori associated
steatorrhea; chronic pancreatitis, bile salt deficiency, small bowel disease
Causes bile salt deficiency
liver disease, bile salt resins, cholestasis, bacterial overgrowth, Crohn's
D-xylose screen
failure to reabsorb xylose indicates small bowel disease
Calcification of pancreas
chronic pancreatitis cause of malabsorption
Celiac disease
autoimmune disease; antibodies against gliadin in gluten; flat villi
Celiac disease
association with dermatitis herpetiformis
Whipple's disease
systemic infection; foamy macrophages with bacteria (PAS+ inclusions) in small bowel submucosa
fever, polyarthritis, skin pigmentation
Invasive diarrhea
Campylobacter jejuni MCC; positive fecal smear for leukocytes
Secretory diarrhea
loss isotonic fluid; enterotoxins from E. coli and V. cholerae
Osmotic diarrhea
hypotonic loss fluid; laxatives, lactase deficiency
MCC diarrhea in children
Norwalk virus
MCC diarrhea in adults
common cause diarrhea in AIDS; MCC cholecystitis and pancreatitis in AIDS
Staphylococcus aureus
preformed toxin causes food poisoning; culture food
Bacillus cereus
preformed toxin in fried rice and tacos; gram positive rods in stool
Clostridium botulinum (adult)
preformed neurotoxin (blocks acetylcholine release); paralysis and mydriasis
Clostridium botulinum (child)
colonization of bowel with release of neurotoxin; eating honey
Clostridium difficile
pseudomembranous colitis; post-antibiotics; toxin assay stool; Rx metronidazole
Shigella sonnei
produces dysentery (bloody diarrhea); associated with HUS
Salmonella enteritidis
gastroenteritis; animal reservoirs - poultry, turtles
Salmonella paratyphi
sepsis; osteomyelitis in HbSS
Salmonella typhi
typhoid fever; human transmission; bradycardia, neutropenia, splenomegaly
Carrier state site
M. tuberculosis
MCC intestinal TB in United States (swallow TB); Peyer's patch site of infection
Enterotoxigenic E. coli
secretory diarrhea (traveler's diarrhea); toxin stimulates guanylate cyclase
Vibrio cholerae
secretory diarrhea; toxin stimulates adenylate cyclase to produce cAMP
Oral Rx cholera
solution must contain glucose to reabsorb Na+ (co-transport)
Yersinia enterocolitica
mesenteric lymphadenitis; sepsis in iron overload states
Entamoeba histolytica
dysentery; trophozoites phagocytose RBCs; liver abscess; Rx metronidazole
Cryptosporidium parvum
MCC diarrhea in AIDS; acid-fast oocysts
Giardia lamblia
MC protozoal cause of diarrhea; cause of malabsorption; Rx metronidazole
Trichuris trichiura
rectal prolapse in children
Enterobius vermicularis
anal pruritus; urethritis in girls; no eosinophilia
Ascaris lumbricoides
intestinal obstruction due to adult worms; no eosinophilia
Necator americanus
hookworm; iron deficiency anemia
Strongyloides stercoralis
rhabditiform larvae in stool not eggs
Diphyllobothrium latum
fish tapeworm; vitamin B12 deficiency
Signs of small bowel obstruction
colicky pain; constipation and obstipation
Radiograph small bowel obstruction
air-fluid levels on x-ray
MCC small bowel obstruction
adhesions from previous surgery
Duodenal atresia
vomiting bile-stained fluid at birth; double bubble sign; Down syndrome
Hirschsprung disease
absent ganglion cells in submucosal/myenteric plexus rectosigmoid
proximal bowel dilated but peristalses; no stool in rectal vault
Hirschsprung association
Down syndrome; Chagas disease
terminal ileum telescopes into cecum; obstruction plus bloody diarrhea
Meconium ileus
complication of cystic fibrosis
Indirect inguinal hernia
second MCC of small bowel obstruction; common in weight lifting
Gallstone ileus
obstruction of small bowel with gallstone + air in biliary tree
MC due to sigmoid colon twisting around mesentery
Direct inguinal hernia
protrudes through center of triangle of Hesselbach; no obstruction
Umbilical hernia
common in black children; may entrap bowel in adults
Sigmoid colon
MC site for polyps, cancer, diverticula
Small bowel infarction
diffuse abdominal pain with bloody diarrhea
Causes small bowel infarction
embolism (atrial fibrillation), thrombosis SMA or SMV
Ischemic colitis
splenic flexure pain with bloody diarrhea
Mesenteric angina
pain in splenic flexure 30 minutes after eating
submucosal dilation of venules in cecum; cause of hematochezia
massive loss of blood per rectum; diverticulosis MCC
Meckel's diverticulum
persistence omphalomesenteric duct
bleeding MC (iron deficiency in children), diverticulitis
Meckel's diverticulitis
mimics acute appendicitis; cannot differentiate without radionuclide scan
Sigmoid diverticulum
diverticulitis MC complication; MCC hematochezia and fistula formation
"left-sided acute appendicitis"
Ulcerative colitis
mucosal/submucosal ulceration; starts in rectum; crypt abscess; ↑ risk adenocarcinoma
left lower quadrant crampy pain with bloody diarrhea
UC associations
primary sclerosing cholangitis, seronegative HLA B27 + spondyloarthropathy
Crohn's disease
transmural inflammation; terminal ileum involved 80%; granulomas; skip lesions
colicky pain and diarrhea; fistulas (anal, bowl to bowel)
Carcinoid tumor
appendix MC site; terminal ileum MC site for carcinoid syndrome
Carcinoid syndrome
liver metastasis; flushing/diarrhea due to serotonin; increased urine 5-HIAA
Tubular adenomas
precursor lesion colon cancer; size and number determine risk of malignancy
Villous adenoma
greatest risk for colon cancer (30%); secrete mucus rich in protein and potassium
Familial polyposis
AD with 100% penetrance for developing colon cancer
Gardner's syndrome
AD, polyposis plus osteomas and desmoid tumors
Turcot's syndrome
AD, polyposis plus brain tumors
Colorectal cancer
second MC cancer and cancer killer in adults
Left-sided colorectal cancer
obstruct; MC location rectosigmoid
Right-sided colorectal cancer
Acute appendicitis
due to lymphoid hyperplasia in children and obstruction by fecalith in adults
External hemorrhoids
Internal hemorrhoids
bleed; prolapse out of rectum
Urobilinogen (UBG)
breakdown product CB in bowel (color of stool)
enterohepatic circulation to liver and kidney (color of urine)
Alcoholic liver disease
serum AST>ALT; ↑ serum GGT
Viral hepatitis
serum ALT>AST
Cholestasis markers
serum AP and GGT
Unconjugated bilirubin
macrophage degradation of heme; lipid soluble; never in urine
Conjugated bilirubin (CB)
water soluble; never normal in urine
% CB <20% (unconjugated)
Gilberts, spherocytosis, physiologic jaundice newborn, ABO/Rh HDN
Gilbert's disease
AD; ↓ uptake and conjugation; bilirubin increases with fasting
Physiologic jaundice newborn
unconjugated hyperbilirubinemia; begins on day three
% CB 20-50%
viral/alcoholic hepatitis
% CB >50%
bile duct obstruction (intra or extrahepatic); carcinoma head of pancreas
Negative urine bilirubin + trace urobilinogen
normal urine
Positive urine bilirubin, absent urobilinogen
obstructive jaundice
Positive urine bilirubin + increased urobilinogen
Negative urine bilirubin + increased urobilinogen
extravascular hemolytic anemia
Markers of severity of liver disease
albumin, PT
Hepatitis A
protective antibodies; day care centers, jails, homosexuals, traveling; not chronic
Hepatitis B
protective antibodies; accidental needle stick, IVDA; hepatocellular carcinoma
Hepatitis C
no protective antibodies; post-transfusion hepatitis; chronic state; hepatocellular carcinoma
Hepatitis D
no protective antibodies; requires HBsAg to replicate
Anti-HBs alone
Anti-HBs + anti-HBc-IgG
recovered from HBV
HBsAg + HBeAg + HBVDNA + anti-HBc-IgM
acute HBV/chronic HBV infective carrier if >6 months
Anti HBc-IgM alone
serologic gap; not infective
HBsAg + anti-HBc-IgM
chronic HBV healthy carrier
Fulminant hepatic failure
viral hepatitis and acetaminophen MCCs
Spontaneous peritonitis
E. coli in adults; S. pneumoniae in children; complication of ascites
Granulomatous hepatitis
TB MC bacteria
Entamoeba histolytica; flash shaped ulcers in cecum; liver abscess; Rx
Echinococcus granulosis; sheep dog definitive host; man intermediate host
Schistosoma mansoni; adult worms in portal vein; "pipe stem cirrhosis"
Clonorchis sinensis; ingesting encysted larvae in fish; cholangiocarcinoma
Congestive hepatomegaly (centrilobular necrosis)
"nutmeg" liver; RHF MCC
Hepatic vein thrombosis
Budd-Chiari syndrome; painful hepatomegaly; ascites; portal hypertension
Portal vein thrombosis
ascites, portal hypertension, no hepatomegaly
Alcohol related disorders
fatty change; alcoholic hepatitis; cirrhosis
Hypertriglyceridemia in alcoholics
↑ synthesis of glycerol 3P (substrate for TG synthesis)
Hypoglycemia in alcoholics
↓ gluconeogenesis (↑ NADH causes pyruvate to convert to lactate)
Ketoacidosis in alcoholics
↑ lactate, ↑ ßOHB (acetyl CoA converted to AcAc and then ßOHB)
Primary biliary cirrhosis
granulomatous destruction triad bile ducts; anti-mitochondrial antibody
Primary sclerosing cholangitis
association with ulcerative colitis; MCC of cholangiocarcinoma
Extrahepatic biliary atresia
neonatal cholestasis
Drugs causing hepatitis
acetaminophen, isoniazid, halothane
Anabolic steroids
intrahepatic cholestasis
Estrogen/oral contraceptives
intrahepatic cholestasis; hepatic adenoma (intraperitoneal hemorrhage)
liver fibrosis, fatty change
Liver angiosarcoma
vinyl chloride
AR; increased iron reabsorption; liver target organ
cirrhosis; "bronze diabetes" - skin pigmentation + destruction of islet cells; malabsorption
↑ serum ferritin, iron, % saturation; ↓ TIBC
Wilson's disease
AR disease; defect in copper excretion in bile and synthesis of ceruloplasmin
cirrhosis, movement disorder (necrosis in putamen), Kayser Fleisher ring (Descemet's membrane)
↓ ceruloplasmin (causes ↓ total copper); ↑ serum/urine free copper
HELLP syndrome
pre-eclampsia; Hemolytic anemia, ELevated transaminases, Low Platelets
AAT deficiency in child
AR, cannot secrete AAT from liver cell; cirrhosis; hepatocellular carcinoma
Reye syndrome
coma and microvesicular fatty change post viral infection; increased ammonia
irreversible fibrosis; regenerative nodules; portal hypertension
Causes cirrhosis
alcohol (MC), HBV/HCV, hemochromatosis, Wilson's, AAT deficiency, 1° biliary
Hepatic encephalopathy
mental status changes; ↑ serum ammonia
Portal hypertension
ascites; varices; splenomegaly; hemorrhoids; caput medusae
Cause of ascites
portal hypertension; hypoalbuminemia; secondary aldosteronism
use aldosterone blocker (acidosis increases loss ammonium in stool)
Hyperestrinism in men
gynecomastia; spider angiomas; female hair distribution
Lab findings cirrhosis
↓ BUN, glucose, sodium, potassium, calcium (↓ vitamin D); ↑ PT
Liver cell adenoma
estrogen related (steroids, oral contraceptives); intraperitoneal hemorrhage
Liver cancer
metastasis MC cancer; lung cancer MC primary site
Hepatocellular carcinoma
chronic HBV and HCV MCC; ↑ AFP; hepatic/portal vein invasion
primary sclerosing cholangitis MCC, C.C sinensis
Pathogenesis of cholesterol stones
bile with too much cholesterol and too little bile salts
Black pigment stones
sign of extravascular hemolytic anemia (spherocytosis, HbSS)
Acute cholecystitis
stone impacted in cystic duct; right upper quadrant colicky pain with radiation to shoulder
Chronic cholecystitis
chemical inflammation
Gallbladder cancer
risk factors - cholelithiasis and porcelain gallbladder
Acute pancreatitis
causes - alcohol and gallstones; ↑ amylase and lipase (more specific)
epigastric pain with radiation into back
Sentinel loop
localized ileus of duodenum due to acute pancreatitis
Pancreatic pseudocyst
abdominal mass; persistence of ↑ serum amylase >1 week
Chronic pancreatitis
alcohol abuse, CF; malabsorption, pain, type I diabetes
Pancreatic cancer
smoking MCC
jaundice/acholic (gray/pale) stools; palpable gallbladder; superficial migratory thrombophlebitis (Trousseau's sign); ↑ CA 19-9
First sign tubule cell dysfunction
inability to concentrate urine
Fixed specific gravity
chronic renal failure; cannot concentrate or dilute urine
Negative urine bilirubin + trace urobilinogen
normal urine
Positive urine bilirubin, absent urobilinogen
obstructive jaundice
Positive urine bilirubin + increased urobilinogen
Negative urine bilirubin + increased urobilinogen
extravascular hemolytic anemia
Positive urine nitrite + positive urine leukocyte esterase
urinary tract infection
Sterile pyuria
positive urine leukocyte esterase but negative standard culture; TB, C. trachomatis
Prerenal azotemia
↑ BUN and creatinine; ↓ renal blood flow (e.g. heart failure, hypovolemia)
Renal azotemia
↑ BUN and creatinine due to intrinsic renal disease (acute tubular necrosis)
Postrenal azotemia
↑ BUN and creatinine due to obstruction to urine flow
Serum BUN:creatinine ratio
<15:1 (renal failure); >15:1 (prerenal or postrenal azotemia)
BUN 80 mg/dL:creatinine 8 mg/dL
ratio 10/1 - renal failure
BUN 80 mg/dL:creatinine 2 mg/dL
ratio 40/1 - prerenal azotemia or postrenal azotemia
Creatinine clearance
measures GFR
important sign of renal dysfunction
RBC casts
nephritic type of glomerulonephritis
WBC casts
acute pyelonephritis, acute tubulointerstitial nephritis
Fatty casts with Maltese crosses
nephrotic syndrome
Hyaline casts
normal unless associated with proteinuria
Renal tubular cell casts
acute tubular necrosis
Waxy or broad casts
chronic renal failure
hexagonal crystals
Horseshoe kidney
Turner's syndrome; lower poles fused
Renal dysplasia
MC childhood cystic disease; abnormal development; flank mass
Maternal oligohydramnios
fetal juvenile polycystic kidney disease; Potter's facies in newborn
Adult polycystic kidney disease
AD; hypertension MC sign; cerebral berry aneurysms
Visceral epithelial cells
synthesize basement membrane
Glomerular BM
negative charge due to heparan sulfate
Nephritic syndrome
oliguria; RBC casts; hypertension; mild to moderate proteinuria
Nephrotic syndrome
proteinuria >3.5 g/day; ascites and pitting edema; fatty casts; fusion of podocytes
linear (anti-glomerular BM antibodies); granular (IC deposition)
MC GN; usually nephritic; episodic hematuria; mesangial IC (lgA-anti-IgA) deposits
Post-streptococcal GN
nephritic; subepithelial deposits; skin/pharyngeal infections; anti-DNAase B
SLE type IV GN
nephritic; subendothelial deposits; anti-DNA antibodies
Crescentic GN
crescents from parietal cell proliferation; worst GN; Goodpasture's, Wegener's
nephritic; anti-BM antibodies (glomerular + pulmonary capillary); crescentic GN
young male with hemoptysis progressing to renal failure
Minimal change disease (lipoid nephrosis)
MCC childhood nephrotic syndrome
Lipoid nephrosis
podocyte fusion; loss of negative charge in glomerular BM
Focal segmental glomerulosclerosis
nephrotic syndrome; AIDS and IV heroin abuse
Membranous GN
MCC adult nephrotic syndrome; subepithelial deposits; epimembranous spikes
Causes membranous GN
HBV, ACE inhibitors, cancer
nephrotic; subepithelial deposits; HCV association; tram tracks
nephrotic; C3 nephritic factor; intramembranous ICs (dense deposit disease)
DM nodular glomerulosclerosis
microalbuminuria first sign
DM glomerulosclerosis
nodules with collagen in mesangium; hyaline arteriolosclerosis of arterioles
ACE inhibitors
inhibit angiotensin II vasoconstriction of efferent arterioles
Alport's syndrome
XD hereditary nephritis with sensorineural hearing loss
Ischemic ATN
prerenal azotemia MCC; renal tubular cell casts; BUN:creatinine ratio <15:1
Ischemic ATN
disruption of BM in proximal tubule and thick ascending limb
Nephrotoxic ATN
aminoglycosides, IVP dye, Pb/mercury poisoning
Nephrotoxic ATN
proximal tubule dysfunction; intact BM
prerenal azotemia, ATN, glomerulonephritis, postrenal azotemia
Acute pyelonephritis
vesicoureteral reflux with ascending infection; WBC casts, fever, flank pain
Chronic pyelonephritis
U-shaped scars overlying blunt calyces
Drug-induced tubulointerstitial nephritis
type I/IV reaction; e.g., penicillin
ARF, fever, rash, eosinophilia, eosinophiluria, WBC casts
Analgesic nephropathy
aspirin plus acetaminophen; renal papillary necrosis; IVP with ring defect
Myeloma kidney
BJ protein produces foreign body reaction in tubules
Urate nephropathy
prevent by giving allopurinol prior to chemotherapy
fixed specific gravity; BUN:creatinine <15:1; waxy and broad casts
Renal osteodystrophy CRF
hypovitaminosis D (no 1-α-hydroxylase); produces osteomalacia
Renal osteodystrophy CRF
osteoporosis from metabolic acidosis
Renal osteodystrophy CRF
secondary HPTH with increased osteoclastic activity
pericarditis, prolonged bleeding time, normocytic anemia, pathologic fractures
Benign nephrosclerosis
kidney of hypertension; shrunken kidneys due to hyaline arteriolosclerosis
Malignant hypertension
renal failure; encephalopathy; BP >210/120 mm Hg; IV nitroprusside
Renal findings
necrotizing arteriolitis; "flea bitten" kidney; hyperplastic arteriolosclerosis
Renal infarction
pale infarcts; hematuria; common in polyarteritis nodosa
renal stone MCC; atrophy of cortex/medulla; postrenal azotemia
Renal stones
most contain calcium (calcium oxalate/phosphate); hypercalciuria MC risk factor
colicky pain radiating into groin, hematuria; x-ray usually shows stone
Staghorn calculus
due to urease producing organisms (Proteus); alkaline urine pH; ammonia smell
hamartoma; associated with tuberous sclerosis
Renal cell carcinoma
smoking MCC; invasion renal vein/vena cava; lung, bone mets; yellow colored
flank mass, hematuria; ectopic hormones (EPO, PTH related peptide), left-sided varicocele
Renal pelvis transitional cell carcinoma
smoking MCC, phenacetin, aniline dyes, cyclophosphamide
Wilm's tumor
hypertension, unilateral abdominal mass in child; aniridia/hemihypertrophy in AD types
Urine draining from umbilicus
persistent urachus
Retroperitoneal fibrosis
produces hydronephrosis
Bladder extrophy
abdominal wall defect + epispadias
Bladder diverticula
most commonly due to prostatic hyperplasia with urethral obstruction
Acute cystitis
E. coli; females > males; no fever, flank pain, or WBC casts
Bladder transitional cell carcinoma
smoking MCC, aniline dyes, cyclophosphamide; papillary
hematuria; hydronephrosis
Bladder adenocarcinoma
risk factors persistent urachus, extrophy
Bladder squamous cell carcinoma
Schistosoma hematobium infection
ventral opening on penis due to failure closure of urethral folds
dorsal opening on penis due to defect in genital tubercle
Peyronie's disease
painful curvature penis due to fibromatosis
persistent/painful erection; HbSS
Squamous cell carcinoma penis
HPV and lack of circumcision most important risk factors
undescended testis; risk for seminoma applies to cryptorchid testis and normal testis
mumps usually unilateral (infertility uncommon)
<35 - N. gonorrhoeae, C. trachomatis; >35 - E. coli, P. aeruginosa
scrotal pain relieved by elevation of scrotum (Prehn's sign)
left-sided scrotal mass; spermatic vein drains into left renal vein; infertility common
may be due to invasion of left renal vein by renal cell carcinoma
persistent tunica vaginalis; scrotum transilluminates
Torsion of testicle
testicle high in canal; absent cremasteric reflex
Testicular cancer
unilateral painless mass that does not transilluminate
Risk factors
cryptorchid testis, Klinefelter's, testicular feminization
MC cancer; radiosensitive; large cells with lymphoid infiltrate; small percentage have ↑hCG
Spermatocytic variant
>65 yrs of age
Embryonal carcinoma
hemorrhage/necrosis; hematogenous spread before lymphatic; ↑AFP, hCG
Yolk sac tumor
MC testicular cancer in boys; ↑AFP
most aggressive testicle cancer; ↑hCG
more often benign in children than adult
teratoma + embryonal carcinoma
Malignant lymphoma
MC type in elderly; metastasis not primary cancer
DHT derived stimulation embryo; periurethral area - hyperplasia; peripheral area - cancer
perineal pain, fever; WBCs at end of voiding
Benign prostatic hyperplasia
DHT/estrogen-mediated; glandular/smooth muscle hyperplasia
all men develop; urethral obstruction MC (hesitancy, dribbling, nocturia), hematuria, dysuria Rx
Prostate cancer
DHT-mediated; palpable with rectal exam; osteoblastic metastasis (↑ AP)
sensitive but not specific for prostate cancer; ↑ in hyperplasia
Kallmann's syndrome
absent GnRH, anosmia, absence of taste
failure to sustain an erection; psychogenic in most cases (erections present at night)
parasympathetic response
sympathetic response
Leydig cell failure
↑ LH; ↓ testosterone, sperm count; normal FSH
Seminiferous tubule failure
↑ FSH (↓inhibin); ↓ sperm count; normal LH and testosterone
Leydig and seminiferous tubule failure
↑ FSH and LH; ↓ testosterone and sperm count
Y chromosome
determines genetic sex
develops seminal vesicles, epididymis, vas deferens
Dihydrotestosterone (DHT)
develops prostate and male external genitalia
Male pseudohermaphrodite
genetic male; phenotypically female
Testicular feminization
XR; deficient androgen receptors; MCC male pseudohermaphrodite
Klinefelter's syndrome
XXY; 1 Barr body; female secondary sex characteristics
Herpes genitalis
recurrent painful vesicles; multinucleated squamous cells with intranuclear inclusions
Human papilloma virus
condyloma acuminata; koilocytosis (wrinkled nuclei surrounded by a halo)
Chlamydia trachomatis
metaplastic squamous cells with vacuoles containing elementary bodies
non-specific urethritis, cervicitis, PID, ophthalmia neonatorum
Neisseria gonorhoeae
urethritis, cervicitis, PID; ophthalmia neonatorum, gram negative diplococcus
Ophthalmia neonatorum first week
N gonorrhoeae
Ophthalmia neonatorum second week
C. trachomatis
Lymphogranuloma venereum
C. trachomatis subtype
scrotal/vulva lymphedema; granulomatous microabscesses; rectal strictures in females
painful ulcer, adenopathy, Hemophilus ducreyi
Granuloma inguinale
Calymmatobacterium granulomatis; raised ulceration but no lymphadenopathy
Treponema pallidum
spirochete; produces vasculitis of arterioles (plasma cell infiltrate)
Primary syphilis
painless chancre
Secondary syphilis
rash on palms/soles; condyloma lata; generalized adenopathy
Tertiary syphilis
neurosyphilis (e.g., tabes dorsalis), aortic arch aneurysm, gummas
reagin antibodies against cardiolipin; ↓ titer with Rx of syphilis
false positive with anticardiolipin antibodies (common in SLE)
confirmatory test for syphilis; not distinguish active from treated disease
remains positive after Rx
Trichomonas vaginalis
flagellate protozoan; cervicitis/vaginitis; Rx metronidazole both partners
Gardnerella vaginalis
vaginal pH >5; bacterial vaginosis; clue cells; Rx metronidazole
Candida vaginitis
white, curd-like discharge; DM, antibiotics, pregnancy; Rx fluconazole
Vulvar squamous cancer
MC vulvar cancer; HPV association
Vulvar leukoplakia
biopsy to R/O squamous dysplasia/cancer
Lichen sclerosis vulva
epidermal atrophy; slight risk for squamous cancer
Squamous hyperplasia vulva
leukoplakia; no cancer risk
Paget's disease
intraepithelial adenocarcinoma (mucin production) of vulva
Malignant melanoma
vulva location; similar to Paget cells but not mucin positive
Gartner's duct cyst
lateral wall vagina; persistent mesonephric duct
Embryonal rhabdomyosarcoma
bloody, grape-like vaginal mass young girl
Vaginal adenosis
maternal exposure to DES; precursor clear cell adenocarcinoma vagina
Vaginal squamous cancer
usually extension of cervical cancer
absence of vagina and uterus
Nabothian cysts
endocervical glands covered by metaplastic squamous epithelium
Pathologic cervicitis
trichomonas, HSV-2, C. trachomatis (follicular cervicitis)
Cervical Pap
superficial squamous (estrogen), intermediate (progesterone), parabasal (no hormone)
70% superficial, 30% intermediate
100% parabasal cells
100% superficial cells
100% intermediate cells
Endocervical cells
sign of adequately performed Pap smear
Cervical polyp
bleeding after intercourse; non-neoplastic
Cervical dysplasia
begins in transformation zone; associated with low and high risk HPV
Risk factors cervical dysplasia/cancer
early onset sexual activity; multiple partners; smoking; OC
cervical intraepithelial dysplasia; mild, moderate, severe (in-situ)
Cervical cancer
↓ incidence (Pap smear); 45-yr-old; COD renal failure from obstruction of ureters
cervical discharge; bleeding after intercourse
Sequence to menarche
breast budding, growth spurt, pubic hair, axillary hair, menarche
Proliferative phase cycle
estrogen-dependent; ↑estrogen inhibits FSH and stimulates LH
day 14-I6; LH surge; subnuclear vacuoles; ↑body temperature
Secretory phase cycle
drop in estrogen/progesterone stimulates apoptosis; plasmin prevents clotting
stimulates follicle and aromatase synthesis in granulosa cells
stimulates androgen synthesis in proliferative phase and progesterone synthesis in secretory phase
Day 21
day of implantation of fertilized egg
↑plasma volume > RBC mass; ↑GFR; ↑thyroxine/cortisol (increased binding proteins)
LH analogue produced by syncytiotrophoblast
stimulates corpus luteum of pregnancy to synthesize progesterone for 8-10 weeks
estrogen of postmenopausal woman; aromatization of adrenal androstenedione
estrogen of non-pregnant woman in reproductive life; aromatization of testosterone
estrogen of pregnancy
↑ FSH (best screen; due to ↓estrogen), ↑LH
secondary amenorrhea, hot flushes
↑ hair in normal areas
hirsutism + male secondary sex characteristics (clitoromegaly)
Test for hirsutism/virilization
↑ testosterone - ovarian source; ↑DHEA-sulfate - adrenal source
Polycystic ovarian syndrome (POS)
↑ LH; ↓ FSH; ↑ estrogen and androgens
hirsutism, oligomenorrhea, infertility; enlarged ovaries with subcortical cysts; LH:FSH >2:1
excess menstrual flow; MCC iron deficiency in women
painful menses; 1° PGF2α, 2° endometriosis
bleeding related to hormone rather than anatomic causes
Anovulatory DUB
menarche and perimenopause; estrogen excess without progesterone
Ovulatory DUB
irregular shedding, inadequate luteal phase
Primary amenorrhea
no menses by 16 years old
Secondary amenorrhea
no menses for 3 months
Amenorrhea-hypothalamic/pituitary dysfunction
↓ FSH/LH; e.g., hypopituitarism
Amenorrhea-ovarian dysfunction
↑FSH/LH; e.g., Turner's syndrome
Amenorrhea-end-organ disease
normal FSH/LH; e.g., imperforate hymen
Asherman syndrome
surgical removal of stratum basalis
Primary amenorrhea-normal secondary sex characteristics
constitutional delay MCC
Primary amenorrhea-lack secondary sex characteristics
Turner's syndrome
XO; no Barr bodies; XO/XY types have gonadoblastomas; streak gonads (no eggs)
newborn with lymphedema hands/feet; cystic hygroma in neck (web); short stature; 1° amenorrhea
Secondary amenorrhea
pregnancy MCC; prolactinoma; anorexia nervosa; pituitary adenoma
Asherman syndrome
removal of stratum basalis causing scarring; secondary amenorrhea
group B streptococcus; intrauterine device (Actinomyces); chronic - plasma cells
Endometrial polyp
menorrhagia; not a precursor for endometrial cancer
functioning endometrial glands and stroma in myometrium; enlarged uterus
functioning glands and stroma outside uterus; reverse menses; ovary MC site
dysmenorrhea, painful stooling, bowel obstruction; "powder burn" appearance
Endometrial hyperplasia
unopposed estrogen; simple/complex types; precursor endometrial cancer
obesity, estrogen Rx, polycystic ovarian syndrome
Endometrial cancer
obesity, nulliparity, estrogen Rx, early menarche/late menopause; OC protective
bleeding in postmenopausal woman
Leiomyoma uterus
menorrhagia, obstructive delivery; not a precursor for leiomyosarcoma
MC sarcoma
Ectopic pregnancy
PID MC risk factor; intraperitoneal hemorrhage; screen with ß-hCG
Follicular cyst
MC ovarian mass in young woman
Risk factors ovarian tumors
nulliparity and genetic factors; OC protective
Serous ovarian tumors
surface-derived; ↑ bilaterality; psammoma bodies in malignant type
Mucinous ovarian tumors
surface-derived; pseudomyxoma peritonei in malignant type
Endometrioid carcinoma
resembles endometrial cancer; association with endometriosis
Cystic teratoma
MC benign germ cell tumor (<1% malignant); hair/teeth; calcifications
MC malignant germ cell tumor; associated with streak gonads of Turners
Yolk sac tumor
MC germ cell tumor young girl; ↑AFP; Schiller-Duval bodies
Meigs syndrome
ovarian fibroma, ascites, right-sided pleural effusion
Granulosa tumor
low grade malignant; hyperestrinism, Call Exner bodies
benign; yellow color; hyperestrinism
Leydig cell and Sertoli cell tumors
XY phenotype of Turner's
Krukenberg tumors
metastatic stomach cancer; signet ring cells
Single umbilical artery
↑ incidence congenital defects
lining of villi; produces hCG and human placental lactogen
Human placental lactogen
responsible for mild glucose intolerance in pregnancy
Abruptio placenta
retroplacental clot; painful bleeding; hypertension, cocaine, smoking
Placenta previa
placenta implanted over cervical os; painless bleeding
Placenta accreta
direct implantation into myometrium without intervening decidua; hysterectomy
Twin placenta
monochorionic always identical twins; dichorionic may be identical or fraternal
Siamese twins
monoamniotic monochorionic twin placenta
Enlarged placenta
DM, Rh HDN, syphilis
Complete mole
benign neoplasm of chorionic villi; dilated villi; no embryo; 46 XX (both male)
preeclampsia in first trimester; ↑ incidence choriocarcinoma
Partial mole
embryo present; 68 XXY; no transformation into choriocarcinoma
malignancy of trophoblastic tissue (syncytiotrophoblast, cytotrophoblast)
Risk factors
complete mole (MC), spontaneous abortion, normal pregnancy
↑hCG; lung metastasis; good prognosis
group B streptococcus (S. agalactiae) infection
abnormal placentation causing placental ischemia; ↑ in vasoconstrictors (ATII)
hypertension, proteinuria, pitting edema; begins in third trimester
Spontaneous abortion
50% have karyotype deformity (trisomy 16)
Amniotic fluid
fetal urine
TE fistula, duodenal atresia, open neural tube defects
infantile polycystic disease
↑ Serum AFP
open neural tube defect
↓ Serum AFP
Down syndrome
Urine estriol
fetal adrenal, placental, maternal liver involved in its production
Down syndrome triad
↑ ß-hCG, ↓ serum AFP, ↓ urine estriol
Fibrocystic change
MC breast mass <50-yrs-old; atypical hyperplasia cancer risk; lumpy, painful breasts
Sclerosing adenosis
component of FCC; involves terminal lobules often has microcalcifications
benign stromal tumor; MC movable mass in women <35-yrs-old
Intraductal papilloma
benign tumor lactiferous duct/sinus; MCC bloody nipple discharge <50-yr-old
Invasive ductal cancer
MCC breast mass in woman >50-yrs-old
Breast cancer risk
unopposed estrogen; family history first-degree relatives
Breast cancer
painless mass upper outer quadrant in woman >50-yrs-old
screening test to detect non-palpable masses
Palpable breast mass
order fine needle aspiration (not a mammogram)
Ductal carcinoma in situ
necrotic centers (comedo); microcalcifications common
Paget's disease of breast
invasive ductal cancer into nipple; Paget's cells similar to vulvar Paget's
Medullary carcinoma
bulky tumor with large cells and lymphoid infiltrate; more common in Pt with BRCA 1 mutation
Inflammatory carcinoma
orange peel appearance; lymphatics blocked by tumor (lymphedema)
Lobular cancer
MC cancer of terminal lobule; ↑ bilaterality
Phyllodes tumor
low grade malignant tumor of stroma
ER-PR positive tumors
tumors responding to hormones; candidate for tamoxifen (anti-estrogen)
ERB-B2 oncogene positive breast cancer
aggressive breast cancer
estrogen stimulation of male breast
normal in newborn, puberty (no surgery), old age; (micronodular) cirrhosis MC pathologic cause
Overactive endocrine syndrome
most often adenomas; use suppression tests (most do not suppress)
Tumors that suppress
prolactinoma (bromocriptine), pituitary Cushings (high dose dexamethasone)
Underactive endocrine syndrome
autoimmune destruction MCC; stimulation tests
Hypopituitarism adults
non-functioning adenoma MCC, Sheehan's postpartum necrosis (stop lactation)
Hypopituitarism in children
craniopharyngioma (Rathke's pouch remnant) MCC; visual field defects
S/S ↓ FSH and LH
amenorrhea, ↓ testosterone in male
Growth hormone functions
muscle growth, gluconeogenesis; release of insulin growth factor (IGF)
synthesized in liver; bone and cartilage growth
S/S ↓ GH/IGF in children
growth retardation; ↓ height and weight
Sleep and arginine infusion
stimulation tests for GH and IGF
S/S ↓ GH/IGF in adults
secondary hypothyroidism; ↓ T4, ↓ TSH; muscle weakness, dry skin
secondary hypocortisolism; ↓ cortisol, ↓ ACTH; fatigue; hypoglycemia
stimulation test for ACTH reserve
blocks adrenal 11-hydroxylase → ↑ ACTH and 11-deoxycortisol (proximal to block)
Metyrapone test ↓ ACTH and 11-deoxycortisol
pituitary/hypothalamic dysfunction
Metyrapone test ↑ ACTH and 11-deoxycortisol
Addison's disease
Diabetes insipidus
loss ADH (central), refractory to ADH (nephrogenic); always diluting urine
Central diabetes insipidus (CDI)
↓ UOsm and ↑ POsm with water deprivation; vasopressin causes ↑ UOsm > 50%
Causes CDI
pituitary stalk transection, hypothalamic lesion (site for ADH synthesis)
Nephrogenic diabetes insipidus (NDI)
↓ UOsm and ↑ POsm with water deprivation; vasopressin causes ↑ UOsm < 50%
Causes NDI
lithium, demeclocycline, nephrocalcinosis, severe hypokalemia
GH secreting pituitary adenoma before epiphyses have fused
GH secreting pituitary adenoma after epiphyses have fused
S/S acromegaly
cardiomyopathy; large hands, feet, jaw; hyperglycemia
inhibited by dopamine
MC pituitary tumor; secondary amenorrhea and galactorrhea; prolactin inhibits GnRH
surgery or bromocriptine (dopamine analog)
Other causes hyperprolactinemia
primary hypothyroidism, drugs
Inappropriate ADH syndrome
hyponatremia <120 mEq/L; ↑ UOsm (always concentrating urine)
small cell carcinoma lung, CNS injury, chlorpropamide
restrict water; demeclocycline in small cell carcinoma
Serum T4
↑ or ↓ in free hormone or thyroid binding globulin (TBG)
↑ Serum T4 and normal TSH
↑ TBG; due to ↑ in estrogen
↑ Serum T4 and ↓ TSH
↓ Serum T4 and normal TSH
↓ TBG; due to anabolic steroids
↓ Serum T4 and ↑ TSH
primary hypothyroidism
↓ Serum T4 and ↓ TSH
secondary hypothyroidism
negative feedback with T4 and T3; best screening test
I131 uptake
↑ in Graves; ↓ in thyroiditis, patient taking excess thyroid, hypothyroidism
Cold nodule
non-functioning nodule; no uptake I131
Hot nodule
functioning nodule; ↑ uptake I131
Thyroglossal duct cyst
midline cystic mass
Branchial cleft cyst
cyst in anterolateral neck
Acute/subacute thyroiditis
painful thyroid; early thyrotoxicosis; ↓ I131 uptake
Hashimoto's thyroiditis
MCC hypothyroidism; HLA Dr3/Dr5; inhibitory IgG TSH receptor antibody
Hashimoto's thyroiditis
↑ anti microsomal and thyroglobulin antibodies
muscle weakness, periorbital puffiness, ↓ reflexes, diastolic hypertension, constipation, dry skin
↓ T4, ↑ TSH
maternal hypothyroidism before fetal thyroid developed, genetic disorder
mental retardation; short stature and increased weight; coarse skin
any cause ↑ thyroid hormone activity; Graves disease, excess hormone, thyroiditis
↑ synthesis thyroid hormone; Graves disease and toxic nodular goiter
Graves disease
autoantibody against TSH receptor (type II reaction); HLA Dr3