Pathology Flashcards
The exception to the rule that pathologic hyperplasia can lead to dysplasia cancer.
BPH: benign prostatic hyperplasia
Major cellular mechanism of cellular hypertrophy
Protein synthesis, gene activation and production of organelles (cytoskeleton, mitochondria)
Permnent tissues cannot undergo hyperplasia or hypertrophy. What are the 3 examples of permanent tissue in the body?
Hyperplasia
- Cardiac muscle
- Skeletal muscle
- Nerve
Classical example of pathologic hyperplasia leading to dysplasia and cancer (female)
Endometrial hyperplasia
Mechanism of atrophy (2)
- Apoptosis (decrease number of cells)
2. Ubiqiquitin-proteasome degradation of cytoskeleton; autophagy (cell size)
Metaplasia most often involves what body surfaces
Surface epithelium
Classical example of metaplasia (GIT)
Barret’s esophagus (squamous–> columnar w/ goblet cells)
What is the mechanism of metaplasia? Is it reversible?
Reprogramming of stem cells; yes
What is the exception to the rule that metaplasia can progress to dysplasia and cancer (female).
Apocrine metaplasia (Fibrocystic change of the breast)
Deficiency of what vitamin can lead to metaplasia, i.e. keratomalacia?
Vitamin A: keratomalacia
t(15, 17) translocation
APML (cells trapped in blast)
* Treatment with ATRA
Mesenchymal tissues can undergo metaplasia. The classical example is:
Myositis ossificans; caused by trauma
(Metaplastic production of bone in the skeletal muscle); look for ossificatiion within the skeletal muscle. This is not an osteosarcoma b/c there is distinct separation
How do you differentiate between osteosarcoma and myositis ossificans on an X-ray?
OS: part of bone
MO: distinct separation of bone from muscle
3 uses of vitamin A in the body
- Night blindness
- Immuno cells
- Specialized epithelium
T/F Dysplasia is reversible
True
Aplasia; classical example
Failure of cellular production during embryogenesis
Hypoplasia; classical example
Decrease in cell production during embryogenesis
Streak ovary in Turner Syndrome
Cell injury occurs when stress ___________
Exceeds a cell’s ability to adapt; type of stress, severity, type of cell affected
Slow progressive decrease in blood supply to the kidney results in _________; whereas a rapid decrease in blood supply results in _______
- Atrophy
2. Infarction
T/F Neurons are very susceptible to hypoxia.
True
Common causes of cellular injury
Inflammation, nutritional deficiency/excess, hypoxia, trauma, genetic mutations
Define hypoxia
Low oxygen delivery to tissue; low ATP; cellular injury
The 3 major causes of hypoxia
- Ischemia
- Hypoxemia
- Decreased O2 carrying capacity of the blood
Define ischemia. Through what 3 mechanisms can ischemia occur?
Decreased blood flow through an organ;
- Arterial flow blockage (atherosclerosis)
- venous outflow obstruction
- Shock (heart, hypovolemic, neurogenic, septic, anaphylactic)
What is Budd Chiari syndrome? What is the most common cause of Budd Chiari syndrome?
Thrombosis of the hepatic vein
* Polycythemia vera (most common cause of Budd Chiari)
What AI disorder is associated with Budd Chiari Syndrome?
SLE; lupus anti-coagulant
Define hypoxemia.
Low partial pressure of O2 in the blood ( PaO2< 60; < 90%)
Describe the sequence of events in oxygenation of the blood.
FiO2 –> PAO2 –> PaO2 –> SaO2
FiO2: high altitude
PAO2: CO2 build up, PAO2 goes down
PaO2: i/s fibrosis lung
Decreased O2 carrying capacity arises with Hb loss or dysfunction. Give several examples.
- Anemia: decrease RBC mass; PaO2 and SaO2 are normal
- CO poisoning [binds Hb 100X > O2]
- Methemoglobinemia
In CO poisoning, is PaO2 normal? Is SaO2 normal?
PaO2 = normal SaO2 = decreased
Exposures to CO
Fires, exhaust from cars, gas heaters
The classic sign of CO poisoning clinically. The first detectable symptom of CO poisoning – good for screening.
Sign: Cherry red appearance of the skin
Symptom: headache
Heme contains Fe2+ iron. Fe3+ cannot bind O2. Metheoglobinemia is seen clinically under these circumstances
Oxidant stress: sulfa drugs, nitrate drugs, newborns
Classic clinical finding in methemoglobinemia. Treatment is:
Chocolate-colored blood with cyanosis
Treatment: IV methylene blue which will reduce iron back to 2+ state
Hypoxia impairs oxidative phosphorylation. The key consequences is that this results in…
Decreased ATP
Low ATP disrupts 3 key cellular functions. Name them.
- Na-K pump [cell swelling]
- Ca pump [high IC Ca can activate enzymes = bad]
- Aerobic glycolysis [lactic acid can denature DNA and proteins]
The initial phase of cellular injury is reversible. What is the hallmark sign of reversible cell injury?
Cellular swelling; leads to loss of microvilli [like blowing up a glove], membrane blebbing [cytoskeleton pulled away from cell membrane] and swelling of RER [ribosomes pop off / decreased protein synthesis]
Reversible or irreversible cell injury: Loss of microvilli, membrane blebbing and swelling of RER (which leads to ribsome detachement and dereased protein synthesis)
Reversible cell injury
Hallmark of irreversible cell damage. The 3 membranes affected.
Cell membrane damage
- Plasma membrane (enzyme in blood, IC Ca increases)
- Mitochondrial membrane
- Lysosome
Where is the ETC? Inner or outer mitochondrial membrane?
The inner mitochondrial membrane
Within the mitochondria, cyotchrome c is present. If it leaks into the cytosol, it can activate…
Apoptosis
Why is high IC calcium dangerous?
It is an enzyme activator
Morphologic hallmark of cell death is…
Loss of nucleus; occurs via pynknosis, karyorrhexis, karyolysis
Pynknosis
Shink of nucleus (ink dot)
Karyorrhexis
Nucleus breaking up into big pieces
Karyolysis
Nucleus pieces broken into building blocks
The 2 mechanisms of cell death
- Necrosis (murder)
2. Apoptosis (suicide)
Necrosis is death of a large group of cells followed by…
Acute inflammation
T/F Necrosis is always pathologic
True
Coagulative necrosis
Necrotic tissue that remains firm; cell shape and organ structure are preserved by coagulation of cellular proteins
* Nucleus disappears; characteristic of all infarction except brain
What is the gross shape of a coagulative necrotic tissue?
Wedge-shaped and pale infarct; wedge points to the occlusion
What is red infarction?
Blood re-enters a loosely organized tissue. Classic example: testicle.
Liquefactive necrosis (3 examples)
Enzymatic lysis of cells and proteins
* Brain (microglial with hydrolytic enzymes), abscess (neutrophils with hydrolytic enzymes), pancreatitis (surrounding = fat necrosis)
Why do we see liquefactive necrosis in the brain?
Because the microglial cells have hydrolytic enzymes.
Gangrenous necrosis is…
Coagulative necrosis (ischemia of lower limb)
- Wet gangrene: superimposed infection (Liquefactive)
- Dry gangrene: mummified tissue
Caseous necrosis
Soft, friable necrotic tissue with cottage cheese like appearance. Combination of C & L necrosis; TB/fungal infection (granulomatous)
Fat necrosis (2 classic examples)
Chalky white appearance (chalky white appearance due to deposition of calcium); peripancreatic fat & trauma to the breast [giant cells, fat and calcification / can present as a mass]
Saponification
Fatty acids released by trauma or lipase join with calcium = dystrophic calcification
Dystrophic calcification
Calcium deposition on dead/dying tissue (serum Ca and PO4 normal); psammoma bodies (tumor cells outgrow blood supply)
Metastatic calcification
Serum Ca or PO4 elevated and has ability to force Ca into tissue and can precipitate
Fibrinoid necrosis. 2 examples
Necrotic damage to BV wall; leaking of proteins into blood vessel wall; results in bright pink staining. Characteristic of malignant hypertension or vasculitis.
In what circumstance would a 30 year old woman present with fibrinoid necrosis?
Pre-eclampsia (3rd trimester)
* Fibrinoid necrosis of the placental blood vessels
T/F Apoptosis is energy-dependent, genetically programmed cell death. Three classical examples.
True
Ex./ endometrium, embryogenesis (syndactly), killing of virally infected cells by CD8 T cells
Apoptotic bodies that fall from cells are removed by…
Macrophages
Apoptosis is mediated by caspases. These caspases activate 2 enzymes
- Protease (break down cytoskeleton)
2. Endonucleases (break down DNA)
The 3 pathways by which caspases are activated.
- Intrinsic mitochondrial (cellular injury, DNA damage, decreased hormonal stimulation) –> cytochrome c leaks and activates caspases
- Extrinsic receptor-lignad (FAS –> CD95 or death receptor) – TNF-TNFR [best example/ NEGATIVE SELECTION of T cells]
- CD8 T-cell pathyway (MHCI –> perforins; granzyme enters pores and activates caspases)
BCL-2’s role
Stabilize the mitochondrial membrane so that cytochrome c does not leak out
Oxygen with 1 e, 2 e, 3 e, 4 e. Which is the most damaging?
- Superoxide
- Peroxide
- Hydroxide (Most damaging)
- Water
Pathologic generation of free radicals
Ionizing radiation (OH), inflammation (PMN’s O2 dept mechanism with burst – NADPH oxidase), metals (copper and iron), drugs (acetaminophen, carbon tetrachloride)
What enzyme converts oxygen into superoxide in the respiratory burst?
NADPH oxidase
H2O2 is converted by ________ to water.
Myeloperoxidase
The fentin reaction generates…
The hydroxyl free radical
Underlying mechanism of damage in hemochromatosis or Wilson’s disease?
Tissue damage 2/2 free radical damage
Free radicals cause this type of damage to a cell
- Lipid peroxidation (membrane)
2. Oxidize DNA and proteins (oncogenesis)
Elimination of free radicals (3 mechanisms)
- Antioxidants (Vitamin A, C, E)
- Enzymes (SOD, glutathione peroxidase, catalase)
- Metal carrier proteins (Cu/cerruloplasmin and Fe/transferrin+ferritin)
Name each enzyme responsible for detoxifying: superoxide, hydrogen peroxide, hydroxyl radical?
- SO dismutase
- Catalase
- Glutathione peroxidase
Describe free radical injury: CCl4 [dry cleaning] and reperfusion injury
CCl4 –> CCl3 [P450] damages hepatocytes & fatty liver (inability to synthesize apolipoproteins that excrete fat)
- Re-perfusion injury: blood returns with oxygen and PMN’s leads to continued injury
Misfolded protein that deposits in EC space, often around blood vessels. What is this protein called?
Amyloid
Congo red stain with apple-green birefringence under polarized light.
Amyloid
Systemic amyloidosis: primary and secondary
Primary: AL (derived from Ig light chain); associated with plasma cell dyscrasia
Secondary: AA (derived from SAA protein – an acute phase reactant); chronic inflammatory states; malignancy; Familial Mediterranean fever
Familial Mediterranean fever
AR dysfunction of neutrophils; high SAA acute phase reactant during acute attacks deposits as AA amyloid; presents with episodes of fever and acute serosal inflammation (MI, appendicitis)
Amyloid classical clinical findings
Kidney = #1: nephrotic syndrome
- Restrictive CM/arrhythmia
- Tongue enlargement, malabsorption, HSM
Senile cardiac amyloidosis; what type of amyloid? Symptomatic?
ASYMPTOMATIC (25% patients > 80 years old); Non-mutated serum transthyretin deposits in the heart
Familial amyloid cardiomypoathy
Mutated serum transthyretin (5% AA) –> restrictive cardiomyopathy
DM2 amyloidosis
Amylin –> pancreas islets (derived from insulin)
Alzheimer’s amyloid plaques made up of
B-myloid precursor protein (a-beta); Chromosome 21 [Down’s Syndrome]
Dialysis associated amyloidosis; what type of amyloid?
Beta-2 microglobulin [component of Ig] deposits in joints; Builds up in blood
MTC amyloidosis
C-cell tumor (calcitonin)
An abscess will have this form of necrosis
Liquefactive
Progeria results from a defect in this protein
Lamin
Wermer syndrome is similar to Progeria, but patients live into their 50’s. The protein defect in these patients is:
Helicase
Lipofuscin deposition in aging cells is 2/2
Peroxidation of membrane liquids
What type of cells have the greatest amount of telomerase activity?
Germ cells
T/F Metastatic calcification can result from ESRD.
True
T/F During pregnancy, the myometrium undergoes smooth muscle hypertrophy
True
Mallory body vs. Councilman body
Mallory body: Intracytoplasmic intermediate filaments within hepatocytes
Councilman body: Extracytoplasmic; apoptosis of a hepatocyte
Define inflammation
Allow PMN’s & Lymphocytes & proteins into tissue space in response to infection
Acute inflammation is characterized by: (2 things)
Edema and PMN’s
Acute inflammation arises in response to (2 events)
Infection or tissue necrosis
Examples of innate responses
Epithelium, mucus, complement, mast cells, macrophages, neutrophils, eosinophils, basophils
Acute inflammation is mediated by several factors.
- TLR’s
TLR’s are present on macrophages and dendritic cells. They recognize ____________.
PAMPS (pathogen associated molecular patterns)
CD__ is present on macrophages and recognizes LPS on outer membrane of GN bacteria
CD14
TLR activation results in upregulation of: _______
NF-kappa B; molecular on-switch which turns on acute inflammatory response
Arachidonic acid is released from the cell membrane by….
PLA2
PGI, D, E mediate vasodilation and increased vascular permeability. Where along the blood vessels do these events occur?
Vasodilation (arteriole) increased vascular permeability (post-capillary venule)
PGE2 mediates…
Feeeeever and pain
LTB4
Attracts and activates PMN’s
LTC, D, E
Mediate vasoconstriction, broncospasm, increased vascular permeability
4 key mediators influencing neutrophil chemotaxis
LTB4, C5a, IL-8, bacterial products
What is a pericyte?
Contains contractile elements underneath endothelial cells. Think leukotrienes.
Where are mast cells? How are they activated (3 methods)?
C/T
- Tissue trauma
- C3a, C5a
- Cross-linking IgE by antigen
Histamine granules mediate (2 functions)
Vasodilation, increased vascular permeability
The delayed response of acute inflammation involves…
Leukotrienes (AA metabolites)
Classical complement
C1 to IgG or IgM bound to Ag
Alternative complemenet
Microbial products directly activate complement
Mannose-binding lectin pathway
MBL binds mannose on microorganisms and activates complement
Result of activation of complement
C3 –> C5 convertase –> MAC
C3a & C5a
C5a
C3b
MAC
C3a & C5a: Mast cell degran
C5a: chemotactic for neutrophils
C3b: opsonin
MAC: lyses microbes by creating holes in cell membrane
Hageman factor (Factor 12)
Activated upon exposure to subendothelial or tissue collagen; also activated in DIC
Hageman factor activates (3)
- Coagulation
- Complement
- Cleaves HMWK to bradykinin [similar to histamine + pain]
2 molecular mediators of pain
PGE2 [feeever/pain] & Bradykinin
Cardinal signs of inflammation and pathophysiology
- Red: vasodilation [histamine, PG, bradykinin]
- Pain: bradykinin and PGE2 – sensitize
- Swelling: vascular permeability (histamine, tissue damage)
- Warmth: vasodilation
- Fever: IL-1, TNF (macrophages) –> COX/hypothalamus (PGEEE2)
Describe the molecular basis of fever
Pyrogens –> Macrophages (IL-1, TNF) –> COX/hypothalamus –> PGE2 increases temperature
The 3 phases of acute inflammation.
- Fluid/Edema
- PMN (24 hours)
- Macrophage (2-3 days)
What is the first step of neutrophil arrival? Second step? Step 3? Step 4?
- Margination [vasodilation slows blood flow in post capillary venules]
- Rolling: cells slow down with selectin speed bumps
- Adhesion
- Transmigration
P-selectin is upregulated by
Weibel-Palade bodies on endothelial cells W = VWF; P = P-selectin
E-selectin is induced by
E-selectin: TNF, IL-1
Selectins bind to __________ on leukocytes
Sialyl Lewis X
Cellular adhesion occurs with CAMS which bind to ________ on neutrophils
Integrins (C5a, LTB4 upregulate)
Leukocyte Adhesion Deficiency
- Defect
- Mode of inheritance
- Classical clinical findings
AR recessive defect of integrins (CD18 subunit)
* Delayed separation of umbilical cord; increased PMN’s; recurrent bacterial infections that lack pus
What is pus?
Dead neutrophils sitting in fluid
Phagocytosis is enhanced by opsonins… (2)
IgG, C3b
Chediak-Higashi Syndrome defect and inheritance
AR protein trafficking defect; phagosome –> lysosome (RR system of MT are defective)
Chediak-Higashi Syndrome clinical features
Increased risk of pyogenic infections, neutropenia, giant granules in leukocytes, defective primary hemostasis, albinism, peripheral neuropathy
What are the 2 ways in which phagocytosed material is killed? Which is more effective?
- O2-dependent [more effective]; HOCl plays key role
2. O2-independent
Oxygen is converted to superoxide by:
NADPH oxidase
Superoxide is converted to H2O2 by:
Superoxide dismutase
H2O2 is converted to HOCL by:
MPO
CGD results in poor oxygen dependent killing 2/2
NADPH oxidase defect (XLR or AR)
CGD patients are most susceptible to infections by catalase positive organisms such as
S. aureus, Nocardia, Aspergillus, Pseudomas cepacia, S. marcessens; no longer have any source of H2O2 (could be salavaged from bacteria)
How do you screen for CGD?
Nitroblue tetrazolium test. Turns blue = NADPH oxidase in tact. Can you convert oxygen to superoxide?
Defective MPO results in an increased risk for what type of infection?
Candida [usually asymptomatic]; normal NBT test
O2 independent killing occurs via…
Enzymes present in 2ndary granules of leukocyte (lysozyme and MBP)
How do neutrophils die within tissue?
Apoptosis
How is acute inflammation resolved?
- Resolution & healing (IL-10 and TGF-beta)
- Continued acute inflammation (IL-8)
- Abscess
- Chronic inflammation
Which 2 cytokines shut down the acute inflammatory process?
IL-10 & TGF-beta
Chronic inflammation stimuli
Persistent infection, AI disease, foreign material, cancer
Activation of T cells requires 2 signals
- Binding of Ag/MHC
2. Second signal [B7 on APC binds to CD28 on CD4 T cell]
The second signal in activation of a CD4+ T cell
- EC Ag phagocytosed and presented via MHC2 (APC)
2. B7 (APC) on CD28 on CD4 T cell
Describe the B7/CD28 interaction
B7 on APC binds to CD28 on the CD4+ T cell
The 2 subsets of cytokines secreted by CD4+ T Cells
- TH1: CD8: IL2 (T cell growth factor), IFN-gamma (macrophages
- TH2: B-cells
IL-4 (IgG/IgE class switching, 5, 10 (inhibits TH1)
Class switching cytokine
IL-4
Role of IL-5
Eosinophil chemotaxis and activation; maturation of B cells to plasma cells and class switching to IgA
IL-10
Inhibits Th1 cells
CD8+ T cells are activated by intra/extracellular Ag
Intracellular Ag
CD8 T cells kill targets with
Perforins, granzyme (induces apoptosis)
- Activates caspase
- Expression of FASL which binds FAS (activates apoptosis)
Naive B cells express surface (2 Ig’s)
IgM and IgD
How are B cells activated? 2 ways
- Ag–> surface IgM
2. B-cell to MHC 2 CD4/ CD40/CD40L
Granulomatous inflammation: the defining feature
Subtype of chronic inflammation: key cell = epitheloid histiocyte [macrophage with abundant pink cytoplasm]; surrounded by giant cells and rim of lymphocytes
Non-caseating granulomas lack _______________. Several examples of NC granulomas.
Central necrosis:
- Reaction to foreign material (implant)
- Sarcoid
- Beryllium exposure
- Crohn’s disease
- Cat Scratch disease
A stellate shaped non-caseating granuloma is caused by… (think ID)
Cat scratch disease
The DDx (2) for a caseating granuloma.
TB (AFB) or Fungal (Silver/GMS)
How are granulomas formed? 3 steps (name the major cytokines)
- Macrophage:CD4+ interaction
- IL-12/TH1 –> IFN-gamma [occurs in both caseating and non-caseating granulomas]
- Macrophage to epitheloid histiocyte
DiGeorge Syndrome is a developmental failure of ____________ due to ____________
3rd and 4th pharyngeal pouches 2/2 22q11 microdeletion
DiGeorge Syndrome p/w
T-cell deficiency (lack of thymus); hypocalcemia (PTH); abnormal heart, great vessels, face
SCID results from defective:
Cell mediated and humoral immunity
Etiologies of SCID include (3)
- Cytokine receptor defects
* 2. ADA deficiency * - MCH Class 2 deficiency
Treatment of SCID
Isolation & stem cell transplant
X-linked agammaglobulinemia
* Most common mutation
Complete lack of Ig 2/2 disordered B-cell maturation
* Bruton tyrosine kinase signalling molecule
X-linked agammaglobulinemia p/w
Bacterial, enterovirus (IgA/mucosal surfaces), and Giardia infections after 6 months of life; live vaccines must be avoided
Common variable immunodeficiency due to:
Patients p/w
Patients at increased risk for
B-cell or T-helper cell defect
- Bacteria, enterovirus, Giardia
- Present late childhood
- AI + Lymphoma
IgA deficiency is the most common Ig deficiency; increased risk of…
Mucosal/viral infections
Which GI disease is associated with IgA deficiency?
Celiac disease
Hyper-IgM syndrome is due to…
Mutated CD40L or CD40 Receptor; second signal cannot be delivered to helper T-cells during B-cell activation * Cytokines necessary for Ig class switching are not produced; recurred pyogenic infections, especially at mucosal sites (IgA, IgG, IgE)
Wiskott-Aldrich Syndrome triad
TBOpenia, Eczema, Recurrent infections (humoral and cell-mediated)
Wiskott-Aldrich Syndrome inheritance and gene defect
X-linked WASP gene
C5-C9 deficiency increased risk for
Neisseria infection
C1 esterase inhibitor deficiency results in
Hereditary angioedema characterized by periorbital edema
The underlying principle of AI disorders
Loss of self-tolerance
Autoimmune polyendocrine syndrome triad
* Central tolerance goes awry AIRE mutation in the medullary epithelial cells in the thymus 1. Hypoparathyroidism 2. Adrenal failure 3. Candida
Positive selection; negative selection in the thymus. What part of the thymus does each occur?
Positive (Cortex): must recognize MHC and self-Ag
Negative (Medulla): bind self-Ag [dendritic cells and medullary epithelial cells]
Central tolerance in the bone marrow
- Receptor editing of light chain (RAG genes reexpressed)
2. Apoptosis
If central tolerance fails, the lymphocyte can still undergo negative selection in the periphery. How does this occur?
The second CD28/B7 signal does not occur. The CD4 T cell can undergo anergy or apoptosis.
CD95
FAS receptor (binds FAS Ligand) induces apoptosis
Autoimmune lymphoproliferative syndrome (ALPS)
- Loss of peripheral tolerance
Mutations in the FAS apoptosis pathway. [FAS, FAS-L, caspase-10]
Tregs suppress immune responses in 2 ways.
- Block CD4+ cells (CTLA-4 on T-reg blocks B7)
2. Cytokines: IL-10 (limits MHC 2 and co-stimulator molecules), TGF-beta (inhibits macrophages)
The 3 types of Tregs.
- CD4+
- CD25+ (IL-2 Receptor)
- FOXP3 (Transcription factor)
CD25 polymorphisms are assoicated with which AI conditions?
MS, DM1 [Tregs]
FOXP3 mutations result in…
IPEX (Immune polyendocrineopathy, X-linked)
* Islets, DM1, diarrhea
Why do AI conditions occur in women of child bearing age?
Estrogen reduces apoptosis of self-reactive B-cells.
PTPN22 gene polymorphisms can result in…
Loss of self tolerance
Tyrosine phosphatase –> signalling mechanisms go awry and AI develops
SLE summary (Type 3 Hypersensitivity)
Decreased CH50, C3, C4
* Ab directed against host nuclear material and the complexes deposit in tissues, activating complement
Early complement deficiency (particularly C2) is associated with..
SLE b/c you need the early complement components to initiate the immune complex clearing process
Aside from a malar rash upon exposure to sunlight, SLE patients can present with this type of rash.
Discoid rash
The pancytopenia seen in SLE patients is a T2 or T3 hypersensitivity reaction?
T2
In Libman-Sacks endocarditis, vegetations on valves are on one or both sides of valves.
Both sides of valves
The 3 anti-phospholipid antibodies that are commonly tested clinically with SLE:
- Anticardiolipin (VDRL/RPR)
- Lupus anticoagulant (falsely elevated PTT b/c interferes with the test)
- Anti-beta-2-glycoprotein I
Antiphospholipid Ab syndrome [associated with SLE, but more commonly not associated with SLE]
Antiphospholipid Ab + hypercoagulable state; Arterial and venous thrombosis
The 3 classic drugs associated with anti-histone Ab+ SLE
- Hydralazine
- Procainamide
- INH
Most common causes of death in SLE (2).
Renal failure (MN or DPGN) and infection
T/F SLE patients have accelerated coronary atherosclerosis.
True
Sjogren’s syndrome: what type hypersensitivity reaction?
Type 4: AI destruction salivary and lacrimal glands (dry eyes, dry mouth, dental caries)
The most common AI condition associated with Sjogren’s syndrome
RA (can have RF in blood)
Anti-ribonucleoprotein Ab
Anti-SSA and Anti-SSB
Sjogren’s syndrome
* associated with extragrandular manifestations
* Risk of neonatal lupus and congenital heart block
Anti-SSA and neonates
Neonatal lupus and congenital heart block
Lymphocytic sialadenitis
Sjogren’s syndrome
Important to biopsy to R/O sarcoidosis, amyloidosis
Sjogren’s syndrome have an increased risk for…
B-cell lymphoma (presents as unilateral enlargement of parotid late in disease course)
Systemic sclerosis (Scleroderma)
AI damage of mesenchyme leads to fibroblast proliferation and collagen deposition
* Endothelin, PDGF, TGF-B
CREST syndrome
Calcinosis (Anti-centromere Ab) Raynaud Esophageal dysmotility Sclerodactyly Telangiectasias of skin
DNA topoisomerase I Ab
Scleroderma
Most common cause of death in scleroderma
Lungs
Mixed connective tissue disease (name the Ab)
SLE, SS, polymyositis
ANA with serum Ab against U1 RNP
ANA with Anti-U1 RNP Ab
Mixed connective tissue disease
T/F Healing occurs via a combination of regeneration and repair.
True
Labile tissues continually regenerate. Give several examples and name where the stem cell layers are.
Bowl (crypts), skin (basal layer), bone marrow
CD34
Marker of hematopoietic stem cell
What is the marker of the hematopoetic stem cell?
CD34
What is the stem cell of the lung?
Type 2 pneumocyte
Stable tissues are quiescent, but can re-enter the cell cycle. Classic example is. Give a second example in the kidney.
Liver: compensatory hyperplasia 2/2 partial resection.
* Also PCT of kidney
Permanent tissues lack significant regenerative potential. The 3 examples:
Skeletal muscle, cardiac muscle, neurons
Repair replaces damaged tissue with a…
Fibrous scar
Why do scars appear on the skin?
Regenerative stem cells of the skin can be lost with a deep laceration
Granulation tissue consists of (3 components)
- Fibroblasts (collagen 3)
- Capillaries (nutrients)
- Myofibroblasts (contracts wound)
Eventually, collagen 3 is replaced with collagen type ___. What converts collagen 3? What is the co-factor?
1
Collagenase removes collagen 3 and requires Zn
Collagen 1
Bone
* Tensile strength
Collagen 2
Cartilage
Collagen 3
Pliable: BV (stretch), granulation tissue, embryonic tissue (stretch)
Collagen 4
Basement membrane
These factors are important in repair/healing. State their purpose. TGF-alpha TGF-beta PDGF FGF VEGF
TGF-alpha: epithelial, fibroblast TGF-beta: FGF, inhibit inflammation PDGF: endothelium, smooth muscle, FGF * FGF: angiogenesis *; skeletal development VEGF: angiogenesis
Healthing by primary intention
Wound edges sutured together (minimal scar)
Healing by secondary intention
Edges are not approximated; granulation tissue fills in the defect (big scar & contraction of wound by myofibroblasts)
Delayed wound healing causes (think biochemistry)
Infection (most common cause)
Vitamin C [hydroxylation proline, lysine] , Cu [lysyl oxidase], Zn (collagen 3–>1)
* foreign body, ischemia, DM, malnutrition
GLY-Proline-Lysine gets hydroxylated in collagen by what cofactor? Why is this necessary?
Vitamin C; necessary for cross-linking
Dehiscence
Rupture of wound; most commonly seen in abdominal surgery
Hypertrophic scar vs. Keloid
Hypertrophic: collagen 1 in a wound
Keloid: Excess collagen 3 outside of wound & way out of proportion (ear-lobe classic location)
How can you determine clonality of cancer cells? What about B cells?
G6PD isoforms (G6PD on X chromosome); Androgen receptor isotypes; Ig light chain [kappa: lambda 3:1]
What is the normal ratio of kappa:lambda in a B cell?
3:1
The 3 DDX for LAD.
- Infection (reactive hyperplasia)
- Lymphoma
- Metastatic cancer
Are benign tumors monoclonal?
Yes
Name the tumors (benign + malignant) Epithelium Mesenchyme Lymphocyte Melanocyte
Adenoma/Adenocarcinoma
Lipoma/Liposarcoma
( ) Lymphoma/Leukemia
Nevus/Melanoma
Causes of death in adults (3 major) & in children (3)
- Cardiovascular disease
- Cancer
- Cerebrovascular
- – - Accidents
- Cancer
- Congenital defects
Most common cancers in adults (incidence): 3
- Breast/prostate
- Lung
- Colorectal
Most common cancers in adults (mortality): 3
- Lung
- Breast/prostate
- Colorectal
Approximately how many cancer divisions occur before the earliest clinical symptoms arise?
30
T/F Each cancer division results in increased mutations. Cancers that do not produce symptoms until late will have undergone additional divisions and mutations. Cancers detected late have a poor prognosis
True
The 2 major goals of cancer screening.
- Catch dysplasia before it becomes carcnioma
2. Detect carcinoma before clinical symptoms arise
Tumor is driven by:
DNA mutations
Cancer: Aflatoxins
HCC
Cancer: Alkylating agents
L/L
Cancer: Alcohol
SCC OP, upper esophagus, pancreatic, HCC
Cancer: Aresnic
SCC skin, lung cancer, angiosarcoma liver
Cancer: Asbestos
Lung cancer; mesothelioma
Cancer: Cigarette smoke
OP cancer, esophagus, lung, kidney, bladder
Cancer: Nitrosamines
Stomach carcinoma
Cancer: Napthylamine
Urothelial carcinoma of bladder
Cancer: Vinyl chloride (PVC pipes)
Angiosarcoma of the liver
Cancer: Nickel, Chromium, Beryllium, Silica
Lung carcinoma
Cancer: EBV
NP carcinoma [Chinese, African], BL, CNS lymphoma (AIDS)
Cancer: HHV-8
KS [endothelial cells]
Cancer: HBV, HCV
HCC
Cancer: HTLV-1
Adult T-cell leukemia, lymphoma
Cancer: HPV 16, 18, 31, 33
SCC vulva, vagina, anus, cervix (AC cervix)
Cancer: ionizing radiation [nuclear reactor]
AML, CML, Papillary carcinoma of the thyroid [hydroxyl free radicals]
Cancer: nonionizing radiation (UVB)
Basal cell carcinoma, SCC, melanoma [pyrimidine dimers in DNA, normally excised by restriction endonuclease]
3 key regulatory systems disrupted in cancer
- Proto-oncogenes
- Tumor suppressor genes
- Regulators of apoptosis
Mutations of proto-oncogenes form…
Oncogene: unregulated cell growth
4 categories of oncogenes
- Growth factors (PDGF)
- Growth factor receptors (EGFR, RET, KIT)
- Signal transducers (RAS, ABL)
- Cell cycle (CDK) and nuclear regulators (MYC)
Cancer associated with PDGF-B mutation
Platelet dervied growth factor: Astrocytoma
Cancer associated with EGFR (Her2Neu) amplification
Breast cancer
Cancer associated with RET point mutation
MEN 2A, 2B [sporadic MTC]
Cancer associated with KIT point mutation
GIST
Cancer associated with RAS gene family
Carcinomas, melanoma, lymphoma (GTP binding protein – inability to cleave RAS GTP to make RAS GDP)
Cancer associated with ABL
t(9, 22) with BCR-ABL [CML and some forms of ALL]
Cancer associated with c-MYC TF
Burkitt’s Lymphoma t(14,18)
Cancer associated with N-MYC TF
Neuroblastoma
Cancer associated with L-MYC TF
SCLC
Cancer associated with cyclin D1
t(11,14) Mantle cell lymphoma
G1-S phase transition
RAS in OFF state = (GDP or GTP)
RAS-GDP
RAS in ON state = (GDP or GTP)
RAD-GTP
Cancer associated with CDK4
Melanoma
Histologic features of Burkitt’s lymphoma
Starry sky appearance
In a lymph node, the 3 areas of B cells include (think lymphoma)
Follicle, Mantle, Margin
The 2 major tumor supressor genes
p53, Rb
p53 regulates which transition in the cell cycle?
G1-S phase transition
BAX
Destroys BCL-2; allows cytochrome C to leak out of mitochondria and cause apoptosis (p53 allows)
Germline mutation in p53 results in what syndrome?
LiFraumeni syndrome: increased risk for multiple types of carcinomas and sarcomas
Rb regulates which transition in the cell cycle
G1-S phase
T/F Phosphorylated Rb is happy. It then releases E2F, which allows G1-S transition.
True
Who phosphorylates Rb?
Cyclin D
T/F A mutated Rb results in constitutively free E2F
True
Sporadic vs. Germline mutation of Rb; unilateral/bilateral
Sporadic: unilateral
Germline: B/L & osteosarcoma
BCL2 overespression occurs in what cancer?
Follicular lymphoma (t(14,18))
Telomerase is a necessary enzyme for cell immortality. Normally telomeres shorten and results in cellular senescence. Cancers have up/downregulated telomerase
Upregulated
T/F Angiogenesis is necessary for tumor growth survival
True
Why does immunodeficiency increase risk for cancer?
Downregulated MHC1 allows for evasion of immune surveillance
T/F Downregulation of e-cadherin can result in cancer spread. What are the next steps?
True
- Lamin (basement membrane)
- Collagenase 4
- Fibronectin
Which carcinomas spread via the blood?
RCC, HCC, choriocarcinoma, Follicular carcinoma thyroid
Omental caking is characteristic of
Ovarian carcinoma
T/F Immunohistochemistry is used to characterize different tumors.
True
Intermeidate filament immunohistochemical stain: Keratin
Epithelium
Intermediate filament immunohistochemical stain: Vimentin
Mesenchyme
Intermediate filament immunohistochemical stain: Desmin
Muscle
Intermediate filament immunohistochemical stain: GFAP
Neuroglia
Intermediate filament immunohistochemical stain: neurofilament
Neurons
Immunohistochemical stain: S-100
Melanoma
Immunohistochemical stain: Chromogranin [Differentiate between the best and worse differentiated types of this tumor]
Neuroendocrine cells
Best: Carcinoid
Worst: SCLC
Grading cancer takes into account the extent of
Differentiation
Staging cancer takes into account
Tumor size
Mets
Nodes
Paget’s disease of the breast indicates an underlying
Ductal carcinoma
Hemangioblastoma of retina, cerebellum, medulla with bilateral RCC
Von Hippel Lindau syndrome (Ch. 3)
Astrocytoma, Retinal Hamartoma, Hypopigmented spots and seizures
Tuberous sclerosis
Perivascular Homer-Wright Rosettes
Medulloblastoma
Pancoast tumor: SCC vs. Adenocarcinoma
SCC
Cafe au lait spots, Lisch nodule with a yellow-brown iris (Chromosome 17)
NF-1
B/L CN8 neuroma, juvenile cataracts (Chromosome 22)
NF-2
Port-wine stain with CN6 palsy
Sturge-Weber Syndrome
Colorectal & brain tumor
Turcot’s Syndrome
Colorectal polyposis and osteoma
Gardner’s syndrome
Microcephaly, micrognathia, polydactly, hypotonia
Patau Syndrome (Ch. 13)
Chromosome of Cri-du-Chat
5
Ank protein (ID)
Legionella
Thickened hyperpigmented skin with velvety texture
Basal cell carcinoma
Stable angina results in reversible/irreversible injury to myocytes?
Chest pain with exertion; reversible injury to myocytes
Stenosis at what % results in angina?
70%
Stable angina shows what on EKG?
ST depression
Which region of the heart muscle is most susceptible to ischemic damage?
Epi, Myo *** Endo
[Subendocardium]
The hallmark of subendocardial ischemia on EKG
ST-depression
Unstable angina results from…
Rupture of plaque: exposure of sub-endothelial collagen; partial occulusion
EKG findings unstable angina
ST-depression
Prinzmetal angina 2/2
Vasospasm of coronary artery
EKG findings Prinzmetal angina
ST-elevation [epicardium BV clamping down]
MI is 2/2
Necrosis of cardiac myocytes [rupture of plaque with TBX and complete occlusion]. Also due to vasospasm, emboli and vasculitis
The most common artery involved in an MI
LAD: anterior wall and anterior interventricular septum
The most sensitive cardiac enzyme marker for an MI
Troponin I [up for 7-10 days]
Why is CK-MB useful as a cardiac enzyme?
Detects reinfarction days after an MI; rises 6 hours after infarction, peaks at 24, normal by 3 days
Treatment of MI
ASA/heparin, O2, nitrates, beta-blocker, ACEi
Following an MI, fibrinolyis or angioplasty can cause… (2)
- Contraction band necrosis (Calcium returns to dead tissue)
- Reperfusion injury (free radicals); cardiac enzymes continue to rise
MI microscopic changes < 4 hours 4-24 hours 1-3 days 4-7 days 1-3 weeks 1 month
< 4 hours: none 4-24 hours: coag nex [dark discoloration] 1-3 days: PMN [yellow] 4-7 days: Macrophages [yellow] 1-3 weeks: Granulation
1 day: Coag nex
—pmns—
1 week: Macrophages
1 month: Scar
Key complication < 4 hours following an MI
Cardiogenic shock, CHF, arrhythmia
Key complication 4-24 hours following an MI
Arrhythmia
Key complication 1-3 days following MI
Fibrinous pericarditis (transmural infarction)
Key complication 4-7 days following MI
Rupture (cardiac tamponade, shunting, papillary muscle – MR)
The papillary muscle of the heart is fed by what artery?
RCA
3 major complications following a healed MI [6-8 weeks following an MI]
- Aneurysm
- Thrombus
- Dressler syndrome (anti-pericardium Ab)
Macroscopic changes following an MI < 4 hours 4-24 hours 1-3 days 4-7 days 1-3 weeks 4+ weeks
< 4 hours: none 4-24 hours: dark discoloration Through 1 week: yellow 1-3 weeks: red band (granulation) >4 weeks: white scar
Can you see fibrinous pericarditis with a subendocardial infarction?
No; only with a transmural infarction
90% of patients who present with sudden cardiac death have pre-existing
Severe atherosclerosis (MVP, CM, cocaine) * Due to sudden ventricular arrhythmia
L-sided CHF etiology
Ischemia, HTN, dilated CM, MI, restrictive CM
What are heart failure cells?
Hemosiderin-iron laden macrophages seen in the lung
The mainstay treatment of CHF
ACEi
What is the underlying pathophysiology of cor pulmonale?
Hypoxic vasoconstriction leads to an overworked RV
Nutmeg liver
RHF
Most common congenital heart defect. Associated with FAS
VSD
Eisenmenger syndrome
Reversal of a L-R congenital shunt: RVH, polycythemia, clubbing
Most common type of ASD. Which one is associated with Down’s Syndrome?
Ostium secundum
* Ostium primum
A split S2 on auscultation
ASD (delayed closure of pulmonic valve)
What is a paradoxical embolus?
DVT –> through an ASD into the systemic circulation
PDA is associated with which maternal infection?
Rubella
The ductus arteriosus connects…
Pulmonary artery and aorta
Holosystolic machine-like murmur
PDA
Eisenmenger syndrome of a PDA results in…
Lower extremity cyanosis
Which drugs close PDA vs. keeps it open
Close: indomethacin (decreases PGE –> PDA closure)
Tetralogy of Fallot results in what type of shunt?
PA stenosis, RVH, VSD, overriding aorta [R–>L]
* Relieved by squatting to increase arterial resistance
The degree of the _________ determines the extent of shunting and cyanosis in a TOF patient.
Stenosis
A boot shaped heart on CXR
TOF
Transposition of the great vessels can be managed (temporarily) with what treatment (non-surgical)
Aorta/Pulmonary artery switched: only survival –> maintain PDA with PGE2
Transposition of the great vessels is associated with what maternal condition?
Maternal diabetes
Truncus arteriosus
Single large vessel arising from both ventricles; truncus fails to divide
Tricuspid atresia is associated with what septal defect?
ASD
Infantile vs. Adult coarctation of the aorta
Infantile: PDA [proximal to the PDA]; associated with Turner syndrome [cyanosis LE]
Adult: not associated with PDA [HTN UE, hypotension LE]; rib notching
Infantile coarctation of the aorta is associated with what syndrome?
Adult form of coarctation of the aorta has what odd association?
Turner syndrome; bicuspid aortic valve
Most common overall cause of bacterial endocarditis.
S. viridans [infects previously damaged valves]
Describe the pathogenesis of subacute bacterial endocarditis
Exposure of subendothelial collagen; thrombotic vegetations (platelets and fibrin); transient bacteriemia leads to TRAPPING of bacteria in vegetations
IVDU acute endocarditis infects which valve?
Tricuspid valve
Key bug that causes endocarditis of prosthetic valves
S. epidermidis
Key bug that causes endocarditis in patients with underlying colorectal carcinoma
S. bovis
Culture negative endocarditis
HACEK
* Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella
Consequences of septic embolization of cardiac emboli.
Janeway lesions: painless
Osler nodes: painful IC deposition
Nonbacterial thrombotic endocarditis can be associated with… (2 conditions)
Hypercoagulable state, underlying adenocarcinoma
Most common form of cardiomyopathy.
Dilated (systolic/bi-ventricular)
High yield causes of dilated cardiomyopathy.
Genetic mutations (AD), myocarditis (Coxsackie), ETOH abuse, drugs (cocaine, doxorubicin), pregnancy
Treatment of dilated cardiomyopathy.
Transplant
AD cause of hypertrophic cardiomyopathy
Sarcomere (beta-myosin heavy chain)
Histologic hallmark of hypertrophic cardiomyopathy
Myofiber disarray
Causes of restrictive cardiomyopathy.
Amyloidosis, Sarcoidosis, Hemochromatosis, Loeffler syndrome (Ascaris), Endocardial fibroelastosis (children)
Loeffler syndrome
Ascaris; can p/w restrictive CM
Restrictive cardiomyopathy EKG findings
Low voltage EKG with diminished QRS amplitudes
Most common primary cardiac tumor in adults
Cardiac myxoma
* Benign mesenchymal proliferation with a gelatinous appearance; abundant ground substance on histology
Where does cardiac myxoma grow and what would the patient p/w?
Pedunculated mass in left atrium; syncope
Benign hamartoma of cardiac ventricular muscle (association with what syndrome – children).
Rhabdomyoma; associated with tuberous sclerosis
Mets to the heart usually results in
Pericardial effusion (breast, lung cancer, melanoma, lymphoma)
Acute rheumatic fever & molecular mimicry. Explain
M proteins resemble proteins in human tissues = molecular mimicry
JONES Criteria
J: Joint problems (mig poly) O: pan carditis N: nodules SC E: erythema marginatum S: chorea
Aschoff body with Anitzkow cells
Rheumatic fever myocarditis: focus of chronic inflammation with Anitzkow cells (histiocytes with caterpillar nucleus)
What is the one thing that will kill a patient with acute rheumatic fever?
Myocarditis; Aschoff body with Anitzkow cells
Chronic rheumatic valvular stenosis involves which valve?
Mitral valve; scarring of the valve with fusion of the commisures
Does bicuspid valve predispose you to AS?
Yes (think adult coarctation of the aorta)
In order to prove rheumatic heart disease, one valve MUST be involved: mitral or aortic.
Mitral
Can microangiopathic hemolytic anemia be caused by aortic stenosis?
Yes
What is the most common cause of aortic regurgitation?
Dilation of the aorta [think aortic aneurysm]
Early, blowing diastolic murmur
AR
Hyperdynamic circulation
Regurgitation of blood, SV increases, SBP increases, DBP decreaes (PP widens); bounding pulses, head bobbing, pulsatile nail beds
Eccentric hypertrophy vs. Concentric hypertrophy
Eccentric: volume overloaded
Concentric: pressure overload
Mitral valve prolapse
Associated with Marfan’s, EDS
Mid-systolic click
MVP
Holosystolic blowing murmur
Mitral regurgitation
Opening snap followed by diastolic rumble
Mitral stenosis
Innermost layer of a blood vessel; Middle and outermost
Tunica intima (endothelial cells on a BM), media (smooth muscle), adventitia (C/T)
Organ ischemia can occur through
Thrombosis, Fibrosis
Giant cell arteritis
> 50 y.o. females; branches of carotid artery [flu like, polymyalgia rheumatica]
Polymyalgia rheumatica
Giant cell arteritis
Bx findings giant cell arteritis
Granulomatous vascultis with intimal fibrosis; segmental vasculitis (negative bx doesn’t always R/O disease)
Takayasu arteritis
Same disease as GCA; adults < 50 years old (young Asian female)
- Aortic arch at branch points
- Pulseless disease
Which large vessel vasculitis is considered pulseless disease in young Asian females?
Takayasu arteritis
Medium vessels arteries involve (what type of artery)
Muscular arteries
Polyarteritis nodosa spares what organ? Is associated with what Ag?
Necrotizing vasculitis; lungs spared; HTN (renal); abdominal pain (mesenteric artery); HbSAg
A string-of-pearls appearance within a context of varying degrees of fibrinoid necrosis and fibrosis is characteristic of which vasculitis?
Polyarteritis nodosa (PAN)
Highlighter pink of a blood vessel wall is characteristic of which type of vascular injury?
Fibrinoid necrosis
Kawasaki disease
Asian children < 4 y.o.; fever, conjunctivitis, rash palms/soles, cervical LAD
* Thrombosis with MI/aneurysm with rupture
Treatment of Kawasaki disease
ASA, IVIG
Under what circumstance do you use ASA to treat a child with a ‘viral’-type illness?
Kawasaki disease
Which vasculitis in children is associated with a palmar/sole rash?
Kawasaki
Buerger disease
Necrotizing vasculitis involving digits; presents with ulceration, gangrene, autoamputation of fingers and toes
- Raynaud phenomenon is often present
- Highly associated with smoking
Wegener’s granulomatosis
Nasopharynx, lungs, kidneys (RPGN); C-ANCA+; cyclophosphamide
Large necrotizing granulomas with necrotizing vasculitis in NP, lungs, kidney; key treatment?
Cyclophosphamide (Wegener’s)
Microscopic polyangiitis is similar to Wegener’s. What are the differences?
Necrotizing vasculits involving multiple organs, lung and kidney
* No NP involvement and no granulomas (P-ANCA)
Churg-Strauss Syndrome is distinguised from microscopic polyangiitis with which 3 features? Both are p-ANCA positive.
- Granulomas
- Asthma
- Eosinophilia
Palpable purpura on buttocks and legs; gi pain/bleeding; hematuria; follows URTi
HSP / IgA Nephropathy
Renal artery stenosis (lab value of importance; finding on CT)
- Increased renin
* Unilateral atrophy
2 high yield causes of renal artery stenosis (elderly male vs. young female)
- Atherosclerosis
2. Fibromuscular dysplasia
Acute renal failure, headache, papilledema
Malignant htn emergency
3 pathologic patterns of arteriosclerosis
- Atherosclerosis [intima]
- Arteriolosclerosis
- Monckeberg medial sclerosis [media]
Hyaline vs. Hyperplasitc arteriolosclerosis
Hyaline: protein
Hyperplastic: smooth muscle
4 most common arteries affected by atherosclerosis
Abdominal aorta, Coronary, Popliteal, ICA
4 modifiable risk factors for atherosclerosis
- HTN
- HLD
- Smoking
- DM
Fatty streak in blood vessels
Seen in teenagers (early atherosclerosis)
Symptomatic atherosclerosis occurs with critical stenosis at what percentage?
70%
Hallmark of atherosclerotic embolus
Cholesterol cleft
Hyaline and hyperplastic; arteriolosclerosis causes
- Hyaline: proteins [pink] - benign HTN/DM (NEG-leaky)
2. Hyperplastic: malignant HTN
Glomerular scarring 2/2 benign HTN.
* Histologic hallmark of arteriole.
Hyaline arteriosclerosis of renal arteriole
Onion-skin hyperplastic arteriolosclerosis is 2/2
Malignant HTN
Flea-bitten appearance of kidney
Fibrinoid necrosis 2/2 malignant hypertension
Monckeberg medial calcific sclerosis
Non-obstructive; non clincally significant; incidental finding on X-ray or Mammography
Aortic dissection is 2/2
What is the histologic hallmark?
Intimal tear 2/2 HTN
* Occurs within the context of pre-existing weakness of the media
Vaso vasorum are present in which tunica in the proximal 10cm of the aorta?
Adventitia
Hyaline arteriosclerosis of vasovasorum; decreased Q to the outer part of blood vessel wall
Sharp, tearing, chest pain that radiates to the back; #1 cause of death
Aortic dissection; Cardiac tamponade (dissection backwards); rupture into mediastinum (hemorrhage); ruptre forwards (renal artery compression)
What is the highest yield cause of a thoracic aneurysm? Complications?
Balloon-like dilation of the thoracic aorta
- Tertiary syphillis; tree-bark appearance of aorta
- Aortic insufficiency (#1), compression of mediastinal structures, thrombosis/embolism
AAA occurs 2/2 atherosclerosis in what part of the aorta?
Below renal arteries, but above the bifurcation
A pulsatile abdominal mass that grows with time. What is the critical size most associated with rupture? What are the S/S of rupture?
AAA
> 5 cm; Hypotension, pulsatile mass, flank pain
T/F Hemangioma often regresses during childhood. Is it blanching?
True; Benign tumor of BV
Yes, blanches (vs. purpura which doesn’t blanch)
Angiosarcoma is a malignant proliferation of endothelial cells. Liver angiosarcoma is associated with…
PVC, Arsenic, Thorotrast
Low-grade malignant proliferation of endothelial cells. Is it blanching?
KS (HHV-8)
* Can involve skin/visceral organs [non-blanching]
KS is seen in… (3 different patient demographics). How do you treat each group?
E. European males (surgery), AIDS (ARV), transplant recipients (decreased IS)
Cystic tunica medial necrosis
Dissection
Rheumatic fever is associated with Aschoff bodies which are…
Noncaseating granulomas with giant cells
Most commmon cause of rhinitis
Adenovirus
Allergic rhinitis is associated with…
Asthma and eczema
Nasal polyps occur in… (3 conditions)
Cystic fibrosis, ASA-intolerant asthma, repeated bouts of rhinitis
Profuse epistaxis in adolescent males
Angiofobroma (benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue)
Nasopharyngeal carcinoma with cervical LAD is associated with which virus in which 2 demographics?
EBV: African children and Chinese adults [pleomorphic keratin-positive epithelial cells in the background of lymphocytes]
Acute epiglottitis caused by which microbe?
H. flu type B [high fever, sore throat, droling, dysphagia, acute airway obstruction]
Croup [hoarse barking cough and inspiratory stridor] is caused by…
Parainfluenza virus
Vocal cord nodules 2/2
Excessive use; myxoid degeneration [resolves with rest]
Laryngeal papilloma is due to which virus? Single/Double; Adults/Children
HPV 6 & 11 [single in adults; multiple in children]
Laryngeal carcinoma risk factors…
ETOH, tobacco
Parietal and visceral pleura are lined by what type of cells?
Mesothelial cells
Spontaneous PTX; tracheal shift
Rupture of emphysematous bleb in a young male [shift toward the side of PTX]
Tension PTX; tracheal shift
Shift to opposite side of injury 2/2 penetrating chest injury
Mesothelioma p/w
Recurrent pleural effusions, chest pain [massive encasement of the lung]
2/2 asbestos exposure
Pulmonary HTN histopathology
- Atherosclerosis of pulmonary trunk
- Smooth muscle hypertrophy
* * 3. Plexiform lesions tuft of capillaries**
Young female p/w exertional dyspnea
Pulmonary hypertension
Familial forms of pulmonary hypertension is associated with inactivating mutations of…
BMPR2 [leads to proliferation of vascular smooth muscle]
* Plexiform lesions
Recurrent PE can lead to…
Pulmonary HTN
ARDS histologic hallmark & CXR classical findings
Leaking of protein rich fluid: hyaline membranes
* White out
Ventilator setting in ARDS
PEEP: positive end-expiratory pressure
Recovery in ARDS can lead to interstitial fibrosis because…
You’ve knocked out the type 2 pneumocytes [stem cells]
Neonatal RDS arises 2/2
- X-ray finding
- Associated with
Inadequate surfactant levels
- Diffuse granularity of lung
- Prematurity L:S ratio (low <2), C-section, maternal DM
Major component of surfactant
Phosphatidylcholine = Lecithin
T/F Steroids promote the development of surfactant.
True
Insulin inhibits/promotes surfactant production
Inhibits
Hypoxemia in a neonate increases the risk for..
Supplemental O2 increases risk for…
Persistence of PDA, necrotizing enterocolitis; supplemental O2 increases risk of free radical injury [blindness]
Radon associated with which cancer…
Lung cancer
In the Western US, you would think of what infectious cause of a coin lesion?
Histoplasma
A benign mass of disorganized lung tissue + cartilage seen as a calcified mass on X-ray
Hamartoma
SCLC: surgical or radiotherapy
Radiotherapy
Lung cancer subtypes (NSCLC)
- Glands/Mucus:
- Keratin pearls/Intercellular bridges
- AC
- Squamous CC
- Large cell
Small cell
ADH, ACTH, LES
Tumors start with “s” are associated with …
- Smokers
- Cental
- Paraneoplastic
Squamous cell carcinoma is associated with which paraneoplastic syndrome?
PTHrP
Most common lung tumor in non-smokers and female smokers
Adenocarcinoma
Bronchioalverolar carcnioma arises from which type of cells?
Clara cells; not related to smoking (PNA like consolidation)
Chromogranin+ lung tumor
Carcinoid [polyp like tumor; nests of cells]
2 types of neuroendocrine tumor in lung
- SCLC (non-well-differentiated)
2. Carcinoid (well-differentiated)
Cannonball tumors on lung imaging is usually indicative of primary malignancy of … (2)
Breast, colon; Mets
Adrenal gland mets primary site of malignancy
Lung
Complications of lung cancer (based on the anatomy of the lung)
Pleural involvement, obstruction of SVC, involvement RLN, phrenic nerve; Horner’s
Which type of lung cancer most commonly spreads to involve the pleura (not mesothelioma)
Adenocarcinoma
Decreased TLC, very low FVC, FEV1, but increased FEV1:FVC is characteristic of…
Restrictive lung disease
Obesity can result in restrictive or obstructive lung disease.
Restrictive
Bleomycin, Amiodarone, Radiation therapy can cause…
(Idiopathic) pulmonary fibrosis
TGF-beta from injured pneumocytes can drive…
Idiopathic pulmonary fibrosis
Subpleural –> Diffuse honeycombing of lung is characteristic of which lung disorder?
Idiopathic pulmonary fibrosis
Pneumoconioses mediated by which cell in the lung?
I/S fibrosis 2/2 small particles chronic exposure; mediated by macrophages
Coal workers pneumoconoisis
Carbon dust seen in coal miners; black lung
Caplan syndrome
Coal workers pneumoconoisis associated with RA
Anthracosis
Build-up of carbon (not clinically significant)
Silicosis increaes risk for which infectious disease?
Exposure to sand-blasting and silica miners; impairs phagolysosome to form –> fibrotic nodules in upper lobes of lung; TB
Aerospace industry exposure: non-caseating granulomas in lung, hilum
Beryllium
Shipyard, construction, plumbers
- Fibrosis lung/pleura
2. Cancer lung/pleura
Long rod-shaped particles with brown beads in the lung (Ferrigunous body)
Asbestos
Asteroid body
Sarcoidosis non-caseating granuloma
AA female p/w dyspnea, cough, elevated ACE, hypercalcemia [1-alpha hydroxylase can activate vitamin D]
Sarcoidosis
Hypersensitivity pneumonitis
Granulomatous reaction to inhaled antigen; p/w fever, cough, dyspnea; chronic exposure to lead to I/S fibrosis
** Eosinophils
4 COPD disorders
Obstruction to getting air out of the lung
- Emphysema
- Chronic bronchitis
- Bronchiectasis
- Asthma
What is the only increased value on spirometry in COPD?
TLC
Chronic bronchitis Reid Index
> 50%
2 types of submucosal glands in the lung; normal ratio in the lung? What index is this called?
Serous, mucinous glands
< 40% [Reid index]
Blue bloaters
Chronic bronchitis
Destruction of alveolar air sacs occurs in what COPD? What is the underlying pathophysiology?
Emphysema
[loss of elastic recoil and collapse of the small airways; balloon vs. shopping bag]
What are the 2 values increased on spirometry in COPD?
TLC, FRC
Chronic bronchitis Reid Index
> 50%
2 types of submucosal glands in the lung; normal ratio in the lung? What index is this called?
Serous, mucinous glands
< 40% [Reid index]
Blue bloaters
Chronic bronchitis
Destruction of alveolar air sacs occurs in what COPD? What is the underlying pathophysiology?
Emphysema
[loss of elastic recoil and collapse of the small airways; balloon vs. shopping bag]
* Protease / anti-protease imbalance
Panacinar vs. Centriacinar emphysema; upper/lower lobes
Panacinar: A1AT deficiency [lower lobes] – ER of hepatocytes
Centriacinar: Smoking [upper lobes – smoke goes up]
Round, purple globules in hepatocytes; associated with emphysema; PAS+
A1AT deficiency
A1AT: accumulation of protein in what organelle of the hepatocyte
Endoplasmic reticulum
Curschmann spirals admixed with Charcot-Leyden seen in…
Asthma;
- Mucus plugging
- Eosinophilic MBP
Nasal polyps are classically seen in allergic rhitinis. Where else can they be seen in adults? Children?
ASA-intolerant: adults
CF: Children
FRC emphysema vs. fibrosis
Emphysema: increased
Fibrosis: decreased
Asthma is defined as…
Reversible airway bronchocontrsiction
T/F Allergens induce Th2 in asthma.
True: Il-4 (class switch), 5 (eosinophils), 10 (inhibts Th1)
Nasal polyps are classically seen in allergic rhitinis. Where else can they be seen in adults? Children?
ASA-intolerant: adults
CF: Children
Permanent dilation of bronchioles and bronchi (larger airways) 2/2 necrotizing inflammation with damage to airway walls
Bronchiectasis; blow out of a straw vs. blowing out of a pipe
T/F bronchiectasis can lead to secondary amyloidosis
True
Conjoined kidneys connected at lower pole; ascension stopped by what artery?
Horseshoe kidney (IMA)
Complication of unilateral renal agenesis
Hypertrophy of existing kidney; hyperfiltration increases risk of renal failure later in life
Oligohydramnios is associated with…
Bilateral renal agenesis; lung hypoplasia; flat face with low set ears (Potter Sequence)
Potter sequence is associated with…
Bilateral renal agenesis; lung hypoplasia, flat face with low set ears and extremity defects
Noninherited, congenital malformation of renal parencyhma characterized by renal cysts and abnormal tissue (cartilage)
Dysplastic kidney
- Non-inherited
What is on the differential for ARPKD?
Dysplastic kidney (non-inherited)
T/F ARPKD can p/w Potter Sequence
True
A baby p/w portal hypertension
ARPKD (hepatic fibrosis)
ADPKD extra-renal manifestations (3 key ones)
Berry aneurysm, hepatic cyst, MVP [increased renin]
AD defect: cysts in medullary collecting ducts w/ parenchymal fibrosis in shrunken kidneys
Medullary cystic kidney disease
Hallmark of acute renal failure
Azotemia
BUN:Cr ratio in pre-renal ARF
> 15; tubular function intact
BUN:Cr ratio in post-renal ARF
2%; urine osmolality < 500 (decreased ability to [urine]
Injury and necrosis of tubular epithelial cells: brown, granular casts in urine
ATN (BUN:Cr < 15)
2 major etiologies of ATN
Ischemic: B/S; PCT & Thick ascending limb of medulla
Toxic: PCT
Toxic etiologies of ATN
AG, lead, myoglobinuria, ethylene glycol, radiocontrast dye, urate
Drug induced hypersensitivity reaction of intersititum and tubules that results in ARF
Acute I/S nephritis
Chronic analgesic abuse, DM, SC disease, sever acute pyelo can cause
Acute papillary necrosis
Alkaline urine with ammonia scent UTI
Proteus
Pyuria with negative urine culture suggests
Urethritis 2/2 Chlamydia trachomatis or N. gonorrhoeae
Pt p/w fever, flank pain, WBC casts and leukocytosis
Pyelonephritis
Chronic pyelo in a child is usually 2/2
VUR
Renal cortical scarring with blunted calyces
Chronic pyelo
Scarring at upper and lower poles of kidney
Chronic VUR
Thyroidization of the kidney
Chronic VUR/pyelonephritis
Colicky pain with hematuria and unilateral flank tenderness
Kidney stone
Ca oxalate, Ca phosphate kidney stone
Most common; hypercalcemia; idiopathic hypocalciura
What type of kidney stone is seen in Crohn’s disease and why?
Ca oxalate stone; Increased absorption of oxalate (binds Ca)
AMP stone that results in a staghorn calculus is generally caused by..
Infection with Proteus, Klebsiella; can develop UTI’s –> surgical removal
Radiolucent kidney stone
Uric acid; treat with hydration and alkalinization of the urine
Cysteine stones are seen in children with
Cystinuria [can also form staghorn calculus]
Staghorn calculus in an adult vs. child
Adult: Proteus, Klebsiella
Child: Cystinuria
Most common causes of ESRF
DM, HTN, glomerular disease
Most common cause of chronic rejection in a lung transplant patient
Destruction of the small airways
Nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy, deposition of urea crystals in skin
Azotemia
EPO produced by what cells in the kidney?
Peri-tubular interstitial cells
2 reasons ESRF patients develop hypocalemia
- Vitamin D
2. HyperPO4 binds free Ca
Osteitis fibrosis cystica
2/2 hyper PTH
Osteomalacia vs. Osteoporosis
Cannot mineralize osteoid; buffered metabolic acidosis from bone Ca
T/F Patients with ESRF can develop cysts in the context of shrunken kidneys while on dialysis.
T
Renal hamartoma comprised of blood vessels, smooth muscle and adipose tissue is increased in frequency in patients with what disorder (also causes seizures)
Renal angiomyolipoma; Tuberous sclerosis
Triad of hematuria, palpable mass and flank pain
RCC
T/F RCC can p/w L varicocele
T (Spermatic vein drains into L renal vein)
What color is gross mass of RCC? Most common subtype?
Yellow; clear cell
Pathogenesis of RCC
Loss of VHL (3P) tumor supressor gene [increased IGF-1 and increased HIF VEGF and PDGF]
VHL disease inheritance & 2 cancers
AD; RCC & hemangioblastoma of cerebellum
RCC typically spreads to which nodes?
Retroperitoneal
Malignant kidney tumor comprised of blastema, primitive glomeruli and tubules and stromal cells in a child [p/w hematuria and HTN]
Wilms Tumor [WT1 mutation]
WAGR syndrome
Wilms, Aniridia, Genital abnormalities, mental and motor retardation
Beckwith-Wiedemann Syndrome
Wilms Tumor, neonatal hypoglycemia, muscular hemihypertrophy, organomegaly (tongue)
Most common type of Lower UT cancer; #1 risk factor
Urothelial carcinoma; polycyclic hydrocarbons, napthylamine, azo dyes, LTM cyclophosphamide, phenacetin
2 distinct pathways of urothelial carcinoma
- Papillary [low to high grade]
2. Flat [Begins as high grade]
Which subtype of urothelial carcinoma is associated with early p53 mutations?
Flat
Urothelial tumors typically display a field defect. What is this?
So many mutations develop over time leads to multifocal nature and recurrence
SCC of the bladder 2/2
Chronic cystitis, Schistosoma hematobium [Middle Eastern Male], long standing nephrolithiasis
Adenocarcinoma of bladder at the dome of the bladder arises 2/2
** Arises from urachal remnant **, cystitis glandularis, extrosphy
Urachus
Yolk sac to fetal bladder [lined by glanduar epithelium]; its remnant can lead to AC of the bladder
Hypercoagulable state in nephrotic syndrome 2/2
Loss of AT3
T/F Minimal change disease can be associated with Hodgkins Lymphoma
True
Disease: Effacement of foot processes of podocytes on EM 2/2 cytokine proliferation. What type of protein is lost?
Minimal change disease [selective loss of albumin]
Most common cause of neprotic syndrome in AA & Hispanics? Common diseases?
FSGS
HIV, heroin, SCD
FSGS immune complex deposits? Yes or No
No: negative IF
Kidney disease associated with HBV, solid tumors, SLE, drugs (ie. NSAIDS, penicillamine)
Membranous Nephropathy
Subepithelial spike and dome appearance; granular IF
Membranous nephropathy
Thick capillary membranes on H&E with tram-track appearance; granular IF [Type I & 2]
MPGN
Type I: subendothelial [HBV, HCV – more often assoc. w tram tracks]
Type II: within BM [Anti C3 nephritic factor Ab / stabalizing Ab]
Anti-C3 nephritic factor Ab (which stabilizes the C3 convertase and overactivates complement)
Type 2 MPGN
Preferential hyaline arteriosclerosis in DM nephropathy in which vessel: afferent or efferent? What treatment is indicated to slow progression of hyperfiltration induced damage?
Efferent; ACE inhibitor helps because you don’t want to squeeze down too much on efferent vessel.
M protein virulence factor and renal disease
PSGN
Subepithelial humps on EM
PSGN
RPGN IF
- GBM [linear]
- Granular
- Vasculitis [negative IF]
Crescent in RPGN is composed of…
Fibrin & macrophages
[Not collagen]
Granular IF means…
Immune complex deposition
Diffuse proliferative GN (with subendothelial deposits) is seen in what systemic AI disease?
SLE
CS vs. Microscopic polyangiitis
IN CS:
- Eosinophils
- Granulomatous inflammation
- Asthma
Isolated hematuria with sensory hearing loss and ocular disturbances
Alport syndrome; inherited defect in collagen 4 (X-linked); thinning and splitting of GBM
Developmental malformation; pancreas forms a ring around the duodenum; risk of duodenal obstruction
Annular pancreas
Premature activation of _____________ leads to activation of other enzymes in acute pancreatitis.
Trypsin
What types of necrosis do you see in acute pancreatitis?
Liquefactive necrosis of pancreas; fat necrosis of peri-pancreatic fat
2 most common causes of acute pancreatitis
- ETOH (contracts sphincter)
2. Gallstones (ampulla)
Automobile accident in child wearing a seatbelt can cause…
Acute pancreatitis.
Measles, mumps or rubella: Acute pancreatitis
Mumps
Lipase or amylase: which is better marker for acute pancreatitis?
Lipase [amylase from salivary gland]
Persisentece of elevated amylase in the face of resolved acute pancreatitis
Pancreatic pseudocyst, abscess
Most common causes of chronic pancreatitis [adults vs. children]
- ETOH: adults
2. CF: children
Pancreatic AC arises from…
Pancreatic ducts
2 major risk factors for pancreatic AC
- Smoking
2. Chronic pancreatitis
Pancreatic cancer at the head of the pancreas can p/w [vs. body/tail]
Painless jaundice, pale stools and a palpable gallbladder; 2ndary DM
Serum tumor marker for pancreatic AC
CA 19-9
Failure to form or early destruction of extrahepatic biliary tree p/w neonatal jaundice and cirrhosis
Biliary atresia
Precipitation of cholesterol or bilirubin in bile results in…
Gallstones; supersaturated, decreased lecithin or bile acids [solublize the choleterol]; stasis
What is the classical drug that can lead to gallstones?
Cholestyramine
Are cholesterol stones radiolucent or radioopaque?
Radiolucent
T/F Estrogen increases activity of HMG CoA reductase.
True
Bilirubin stones are radiolucent or opaque?
Opaque
6 key complications of gallstones
- Biliary colic [waxing/waning]
- Acute cholecystitis
- Chronic cholecysitis [Rokitishinky-Ashoff sinus]
- Gallbladder cancer
- Ascending cholangitis (GNR)
- Gallstone ileus
Lab value increased in acute cholecysitis [besides WBC]
Increased ALP
Rokitishinky-Ashoff sinus
Chronic cholecystitis; mucosa diving down into the smooth muscle
Late complication of chronic cholecystitis seen on X-ray
Porcelain gallbladder [dystrophic calcification]
A gallstone ileus can lead to …
Fistula formation b/t the gallbladder and duodenum
Cholecystitis in an elderly woman raises suspicion for…
Adenocarcinoma of the gallbladder
Is UC bilirubin water soluble?
No
Pitch black liver; what other condition has the same pathophysiology, but no black liver?
Dubin-Johnson Syndrome
* Rotor syndrome
Pruritis in obstructive jaundice is 2/2
Plasma bile acids
Viral hepatitis caused by viruses other than hepatitis…
EBV, CMV
Which hepatitis virus in a pregnant woman is most worrisome?
HEV
First serologic marker to rise in acute HBV infection; its presence >6 months defines chronic state
HBsAG
The presence of which Ab defines resolved or immunized HBV infection?
HBsAB IgG
HDV co-infection vs. superinfection. Which is more severe?
Superinfection (different times) is more severe than co-infection (same time)
Fibrosis in cirrhosis is mediated by which type of cell?
Stellate cell (TGF-beta)
Can cirrhosis lead to hypersplenism?
Yes
3 patterns of pathology seen in alcoholic liver disease
- Fatty liver
- ETOH hepatitis (acetaldehyde)
- Cirrhosis
Damaged intermediate filaments within hepatocytes
Mallory bodies
AST or ALT is located in the mitochondria?
AST
Damage in hemochromatosis is caused by…
Free radicals (Fenton reaction)
The key regulatory step in iron absorption
Enterocyte [C282Y mutation in HFE]
Cirrhosis, secondary DM, bronze skin, cardiac arrhythmia and gonadal dysfunction
Hemochromatosis
Brown pigment in hepatocytes; one stains blue with Prussian blue
Iron vs. Lipofuscin (not blue)
ATP7B gene mutated in…
Wilson disease
Treatment of Wilson disease
D-penicillamine
AI granulomatous destruction of intrahepatic bile ducts. Which antibody?
PBC; anti-mitochondrial Ab
Inflammation and fibrosis of intra and extra-hepatic bile ducts; leads to periductal fibrosis with onion-skin appearance, beaded on imaging
PSC
p-ANCA & UC association with which hepatic disease?
PSC
PSC patients have an increased risk for
Cholangiocarcinoma
Pathophysiology of Reye’s syndrome
Mitochondrial damage of hepatocytes
What type of benign tumor of hepatocytes is associated with OCP usage?
Hepatic adenoma
T/F HCC can lead to Budd-Chiari syndrome
T
Hepatomegaly with a nodular free edge of the liver raises suspicion for…
Mets to the liver
Failure of facial prominennces to fuse
Clef lip and palate
Painful, superficial ulceration of oral mucosa. Arises in relation to stress, but often recurs. Characterized by grayish base surrounded by erythema
Aphthous ulcer
Syndrome of recurrent aphthous ulcers, genital ulcers and uveitis. Due to immune complex vasculitis involving small vessels
Behcet syndrome
Virus that remains dormant in the ganglia of the trigeminal nerve.
Herpes-1
Major risk factors for SCC mouth (floor of mouth)
Tobacco, ETOH
Leukoplakia vs. Erythroplakia (Which is most associated with squamous dysplasia?
Must bx to r/o carcinoma.
Erythroplakia (angiogenesis)
Oral hairy leukoplakia on the lateral aspect of the tongue is due to what virus? Any risk for cancer?
EBV in AIDS patients (no increased cancer risk)
Orchitis, pancreatitis, aspetic meningitis associated with what virus?
Mumps
Does an elevated amylase in a patient with mumps suggest pancreatitis?
Not necessarily (salivary amylase)
Inflammation of salivary gland usually due to S. aureus infection is called
Sialadenitis
Benign tumor of stromal (cartilage) and epithelial (glands) tissue of salivary gland which presents as a mobile, painles, circumscribed mass at the angle of the jaw
Pleomorphic adenoma
Why is there a high rate of recurrence of a pleomorphic adenoma?
Irregular margins
Benign cystic tumor with abundant lymphocytes and germinal centers; arises in parotid
Warthin tumor
Malignant tumor composed of mucinous and squamous cells. Usually arises in parotid and involves the facial nerve
Mucoepidermoid carcinoma
Congenital defect resulting in connection between esophagus and trachea is called:
TEF; polyhydramnios
- Vomiting
- Polyhydramnois
- Abdominal distension
Thin protrusion of esophageal mucosa, most often in the upper esophagus results in obstruction. P/W dysphagia for poorly chewed food.
Esophageal web [increased risk SCC]
Esophageal web, beefy-red tongue (2/2 atrophic glossitis), severe iron deficiency anemia
Plummer-Vinson syndrome
Outpouching of pharyngeal mucosa through an acquired defect in the muscular wall; arises above UES at junction of esophagus and pharynx. P/W dysphagia, obstruction and halitosis
Zenker diverticulum
A Zenker diverticulum is a true or false?
False
Painful hematemesis in an alcoholic or bulemic patient
Mallory-Weiss Syndrome
Boerhaave syndrome
Rupture of esophagus; air in mediastinum (SC emphysema)
Dilated submucosal veins in the lower esophagus 2/2 portal hypertension. Painless hematemesis.
Esophageal varices
Most of the esophageal venous blood drains into the _________________ which then drains into the SVC
Azygous vein
The left gastric vein drains into the _______________________.
Portal vein
Painless vs. painful hematemesis
Painless: esophageal varices
Painful: MW
1 cause of death in cirrhosis
Esophageal varices
Disordered esophageal motility with inability to relax LES; 2/2 damaged ganglion cells in myenteric plexus. Known infectious association?
Achalasia [Bird-beak sign]
* Chagas disease
Bird beak sign on barium swallow
Achalasia
Where is the myenteric plexus?
In the muscularis layer between the inner circular and outer longitudinal muscular layers
Chagas disease an the esophagus
Achalasia
High LES pressure on esophageal manometry
Achalasia
Sliding hiatal hernia [hourglass appearance]
Stomach herniates upward into the esophagus
T/F Hiatal hernia is a risk factor for GERD
True
Para-esophageal hernia
Much less common; bowel sounds in lower lung fields.
Bowel sounds in lower lung fields as well as lung hypoplasia is usually due to:
Paraesophageal hiatal hernia
Adult onset asthma usually 2/2
GERD [heartburn, tooth erosion]
How can strictures appear in the esophagus?
Mucosal ulceration in GERD healed by fibrosis
Most common esophageal cancer worldwide
SCC esophagus [ETOH, tobacco, hot tea, achalasia, web, injury]
Lymph node spread: upper, middle, lower 1/3 esophagus
Upper: cervical
Middle: mediastinal or tracheobronchial
Lower: Celiac or gastric
Congenital malformation of the abdominal wall; leads to exposure of abdominal contents
Gastroschisis
Persistent herniation of bowel into the umbilical cord 2/2 failure of herniated intestines to return to body cavity. Contents are covered by peritoneum and amnion of UC
Omphalocele (Seeled)
Congenital hypertrophy of pylorus p/w projectile non-bilious vomiting 2 weeks. Visible peristalsis; olive-like mass in abdomen.
Pyloric stenosis
Acid damage to gastric mucosa 2/2 imbalance between mucosal defenses and acidic environment
Acute gastritis
Curling vs. Cushing ulcer
Curling: burn
Cushing: increased ICP
Why do critically ill patients get gastric ulcers?
- Hypovolemia leads to decreased clearance of acid and decreased mucosal protection
- Increased ICP: Inc. ACh
3 receptors on parietal cells that can increase acid production
- Gastrin
- Histamine
- ACh
Erosion vs. ulcer
Erosion: loss of epithelium
Ulcer: loss of mucosal layer
AI destruction of parietal cells of body/fundus. Type 4 hypersensitivity. Antibodies are a side-effect of the damage
Chronic gastritis
- Atrophy of mucosa
- Achlorhydria [increased gastrin and G cell hyperplasia]
What are the 4 key regions of the stomach?
Cardia, fundus, body, antrum
Chronic inflammation of the stomach increases risk for…
Intestinal metaplasia (Peyer’s pataches) and gastric AC
Describe the underlying reason for intestinal metaplasia in the stomach with chronic gastritis.
Peyer’s patches/inflammation
Does H. pylori invade? What is the most common location in the stomach?
No; antrum
What type of lymphoma is associated with H. pylori?
Marginal zone (MALT)
Epigastric pain that improves with meals
Duodenal ulcer
Brunner glands
Produce mucus; hypertrophied in duodenal ulcer
Posterior duodenal ulcer rutpure can lead to (2):
Acute pancreatitis; gastroduodenal artery bleeding
Which artery bleeds in a ruptured gastric ulcer?
Left gastric artery (lesser curvature)
2 subtypes of gastric AC & risk factors
Intestinal: large, irregular ulcer (lesser curvature of antrum) – metaplasia, nitrosamines smoked foods, blood type A
Diffuse: signet ring/linitis plastica (desmoplasia: reactive stromal response); not associated with H.pylori, nitrosamines, blood type A
Intestinal gastric AC is associated with blood type
A
Acanthosis nigricans [axillary] or Leser-Trelat sign [dozens of subheroic keratoses] can be associated with which type of cancer?
Gastric AC
Left supravlavicular LAD
Gastric AC
Krukenburg tumor seen with which subtype of gastric AC?
Diffuse gastric AC
Sister Mary Josheph nodule seen with which subtype of gastric AC?
Intestinal gastric AC
Congenital failure of small bowel to canalize is associated with what syndrome?
Duodenal atresia; Down Syndrome
Double-bubble sign on AXR
Duodenal atresia (bilious vomiting); polyhydramnios
Meckel diverticulum is a true/false?
True; arises due to failure of vitelline duct to involute [nutrients]
Passing meconium thorough the umbilicus
Failure of vitelline duct to involute 100%
Rule of 2’s
2% population, 2 inches long, 2 feet from IC valve; 2 y.o., bleeding/volvulus/intussuception/obstruction
Twisting of bowel along mesentary; classical locations in adult vs child
Volvulus (obstruction and infarction)
- Adult: sigmoid colon
- Child: cecum
Telescoping of proximal segment of bowel into distal. P/W currant jelly stools. Common causes in children and adults
Intussception; children = lymphoid hpyerplasia [ileum with many Peyer’s patches]; adults = cancer
T/F Small bowel is susceptible to ischemic injury
True; p/w abdominal pain, bloody diarrhea, decreased bowel sounds
Marked hypotension can result in transmural or mucosal infacrction of small intestine?
Mucosal
HLA DQ2, DQ8 is associated with which small bowel disease?
Celiac disease
The role of tissue transglutaminase in celiac disease?
Deaminates glaidin
Dermatitis herpetiformis
IgA deposition at tips of dermal papillae; Celiac disease
Anti IgA Ab: endomysium, TTG, gliadin [can tests IgG in IgA deficiency patients]
Celiac disease
Flattening of villi, hyperplasia of crypts with epithelial lymphocytes
Celiac disease
Damage in celiac disease is typically in what part of the intestine?
Duodenum
Small bowel carcinoma and T cell carcinoma can present in patients with…
Celiac disease (refractory despite good dietary control)
Enteropathy associated T cell lymphoma
Celiac disease
Damage in tropical sprue is most prominent in what part of intestine?
J, I. (Duodenum in celiac disease)
Folate abosrbed
Jejunum
B12 absorbed
Ileum
PAS+ organisms in macrophage lysosomes of the gut
Whipple disease [LP of small bowel]
Whipple disease p/w
Arthritis, valves, LN, CNS; Fat malabsorption & steatorrhea (lots of macrophages in LP, can’t bring in the chylomicrons)
Abetalipoproteinemia
B-48: chylomicron
B-100: VLDL, LDL
Chromgranin+ means
Neuroendocrine tumor
Neuroendocrine tumor of the gut occurs in what part of the gut
Carcinoid tumor; small bowel
Once a carcinoid tumor mets to the liver, it creates a patient who p/w
Bronchospasm, flusing, diarrhea [carcinoid syndrome]
What are 2 triggering factors of carcinoid syndrome?
ETOH, Emotional stress
Appendicitis in child vs. adult is 2/2
Child: lymphoid hyperplasia
Adult: fecalith
Lead pipe sign vs. string sign on imaging
Lead pipe: UC
String sign: Crohn’s
Smoking UC vs. Crohn’s
UC: protective
Crohn’s: increases risks
Crypt abscess on histology with pseudopolyps and loss of haustra
UC
P-ANCA is positive in what bowel disease?
?UC
Bloody diarrhea: UC or Crohn’s
UC
Granulomas: UC or Crohn’s
Crohn’s
Cobblestoning: UC or Crohn’s
Crohn’s
Stricturing and creeping fat: UC or Crohn’s
Crohn’s
Malabsorption: UC or Crohn’s
Crohn’s
Lead pipe sign in UC 2/2
Loss of haustra
Hirschsprung disease is associated with what syndrome?
Down Syndrome
Down Syndrome: small and large bowel
Small: duodenal atresia
Large: Hirschsprung disease
Congenital failure of ganglion cells to descend [neural crest]
Hirschsprung disese
Meissner’s vs.
Aurebach’s mysenteric plexus
Meissners: SM [blood flow, secretions]
Auerbach’s: peristalsis and relaxation
Rectal suction biopsy reveals a lack of ganglion cells in Hisrschprung disease because…
Must look at submucosa
Colonic diverticulum involves which layers?
Mucosa, Submucosa
Colonic diverticulum arises 2/2 in what location?
Wall stress, constipation, low fiber; where vasa recta traverse the muscularis propria – weakened wall [sigmoid colon]
Air or stool in the urine
Recto-vesico fistula 2/2 diverticulitis
Hematochezia in an older adult in Right colon 2/2 acquired malformation of mucosal and submucosal capillary beds
Angiodysplasia
AD disorder resulting in thin-walled blood vessels in nasopharynx and GIT
Hereditary teleangiectasia
Ischemic damage to the colon, usually at the splenic flexure 2/2
Atherosclerosis of SMA; post-prandial pain and weight loss
T/F Hyperplastic polyp of L colon is benign with no malignant potential. Has a serrated appearance on BX.
True
T/F Adenomtous polyp is premalignant
True
Describe the sequence of colon cancer development.
APC—>K-ras–>p53/inc. COX
APC is on chromosome
5
What over-the-counter drug can actually protect against colon cancer?
Aspirin (COX expression at the terminal end of adenoma-carcinoma sequence along with p53 mutation)
> 2cm, sessile, villous adenomatous colon polpy: increased or decreased theoretical cancer risk
Increased [villous = villian]
AD or AR: FAP
AD: Ch. 5
FAP with fibromatosis and osteoma
Gardner’s syndrome (retroperit + bone)
FAP with CNS tumors (medulloblastoma and glial tumor)
Turcot syndrome
Sporadic hamartomatous benign poly that arises in children <5 y.o.; usually presents as soliarty rectal polyp that prolapses and bleeds
Juvenile polyp [large numbers in stomach and colon raise cancer risk]
Hamartomatous polyps throughout the GIT with mucocutaneous hyperpigmentation on lips, oral mucosa and genital skin (AD)
Peutz-Jeghers Syndrome: increased risk for breast, colorectal and GYN cancer
2 pathways of colon cancer
- Adenoma-carcinoma
2. MSI (MMR)
Inherited mutation in DNA MMR repair enzymes; increased risk for colorectal, ovarian and endometrial carcinoma (Colorectal arises de novo R-sided)
HNPCC
Decreased stool caliber, LLQ pain, blood-streaked: L or R colon ca
L
Fe-deficiency anemia, vague pain: L or R colon ca
R
Serum tumor marker for colon ca
CEA
Breast is embryologically derived from
Skin
Breast tissue can develop anywhere along
Milk line
All ducts and lobules are lined by:
Luminal cell layer and myoepithelial cell
T/F Breast tissue is hormone sensitive
T
Anatomically, the highest density of breast tissue
UOQ
Acute mastitis 2/2 breast feeding usually caused by..
S. aureus
Subareolar mass with nipple retraction; Highly dependent on vitamin A; squamous metaplasia in the breast seen in a smoker.
Periductal mastitis
Green-brown nipple discharge; inflammation of subareolar duct presents in multiparous post menopausal woman [plasma cells]
Mammary duct ectasia
Fat necrosis [calcifications and giant cells] of breast that shows up as calcification on mammography 2/2
Trauma
Cystic dilation of mammary ducts and/or terminal duct in a pre-menapausal woman (lumpy bumpy blue dome cyst)
Fibrocystic change
Fibrocystic change: fibrosis, cysts and apocrine metaplasia. Any risk of ca?
No!
Fibrocystic change: ductal hyperplasia & sclerosing adenosis. Any risk of ca?
Yes: 2x invasive carcinoma in either breast
Fibrocystic change: atypical hyperplasia. Any risk of ca?
Yes: 5x invasive carcinoma in either breast
Can sclerosing adenosis be calcified on mammography?
Yes
Benign breast growth that bleeds in a pre-menapausal woman. What cells do you see?
Intraductal papilloma; fibrovascular core see both epithelial cells and myoepithelial cells
How do you differentiate a benign intraductal papilloma from papillary carcinoma?
Ca: only one cell type [no myoepithelial cells] also in an older woman
Tumor of fibrous tissue and glands; well circumscribed “mouse in the breast” that is estrogen sensitive in a pre-menopausal woman
Fibroadenoma
Fibroadenoma-like tumor with overgrowth of fibrous component; leaf-like projections in post menopausal women
Phyllodes tumor
Major risk factor for breast cancer
Estrogen exposure
* Female, age, early menarche/late menopause, obesity, atypical hyperplasia
DCIS that reaches the nipple
Paget’s disease of the breast
Major types of breast cancer
DCIS, LCIS
What type of DCIS has high-grade cells with necrosis and dystrophic calcification in center of ducts?
Comedo type of DCIS
How is DCIS seen on mammography?
Calcification
3 potential pathologies of calcification on mammography?
- Fat nex
- Sclerosing adenosis
- DCIS
Most common type of invasive carcinoma of breast that p/w breast mass detected by PE or mammography
Invasive ductal carcinoma
Duct-like structures in desmoplastic stroma of breast bx
Invasive ductal carcinoma
Subtypes of invasive ductal carcinoma
Tubular carcinoma
Mucinous carcinoma
Medullary carcinoma
Inflammatory carcinoma
Subtype of invasive ductal carcinoma with a good prognosis
Tubular carcinoma
Subtype of invasive ductal carcinoma with a good prognosis seen in elderly women
Mucinous carcinoma
Subtype of invasive ductal carcinoma that p/w an inflammed breast that does not resolve with ABX; bx cancer w/in dermal lymphatics
Inflammatory carcinoma
- Clincopathologic
- DDX acute mastitis
Subtype of invasive ductal carcinoma seen in pts with BRCA1 mutations
Medullary carcinoma
Underlying pathology in LCIS
Dyscohesive cells lacking e-cadherin
BRCA & E-cadherin
LCIS
Multifocal and B/L: DCIS or LCIS
LCIS
What type of breast cancer is often discovered incidentally?
LCIS [Tamoxifen and close follow-up]
Breast cancer that grows in single-file pattern?
E-cadherin / invasive lobular carcinoma
Most patients with BRCA don’t p/w mets. Therefore, the most useful factor in prognosis is…
Spread to axillary LN
T/F Her2Neu is a cell surface receptor proto-oncogene.
T
Triple negative cancer: positive or negative PGX. What demographic of women?
Negative: AA women
BRCA1 or BRCA2: Breast cancer in males. What other syndrome?
BRCA2; Klinefelter syndrome
BRCA1 mutations associated with which 2 cancers?
Breast, ovarian serous
Highest density of breast tissue in a male
Sub-areolar
Males develop ductal or lobular carcinoma
Ductal (males don’t develop lobules)
