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Hyperplasia
Metaplasia
Dysplasia
- Reversible
- Reversible
- Reversible
- Pathologic hyperplasia
can progress to cancer
- Etiology:
- Etiology:
- Etiology:
Physiologic (ex Vit A deficiency
Long standing
pregnancy)
(keratomalacia,
pathologic hyperplasia
Pathologic (ex - )
myositis ossificans)
or metaplaisa
Cellular stress (barret's
esophagus)
Processes
Properties
Hyperplasia
and
Hypertrophy
Atrophy
Metaplasia
Aplasia
Hypoplasia
Fig keratomalacia.
3.
-
3. Explain necrosis
Necrosis occurs as a result of acute inflammation to a large group of cells and is always pathologic
Types
1. Coagulative necrosis
2. Liquefactive necrosis
3. Gangrenous necrosis - dry and wet
4. Caseous necrosis
5. Fat necrosis
6. Fibrinoid necrosis
4. Describe coagulative necrosis
- Cell and organ structure is preserved by coagulation of cellular proteins
- Characteristic of ischemic infarction of any organ except brain
Fig - right is normal glomerulus and left is coagulative necrosis of glomerulus. Note cellular
and organization structure is preserved with loss of nucleus.
- Area of infracted tissue is often wedge shaped and pale. Wedge points to the blocked blood
vessel.
5. When does red infraction (hemorrhagic infraction) occur?
Red infraction occurs when blood reenters a loosely organized tissue. Ex - ischemia of testis, lungs.
(is red infraction a type of coagulative necrosis?)
6. Describe liquefactive necrosis
- Necrosis in which enzymatic lysis of cells and proteins result in liquefaction
- Characteristic of brain (microglial cells destroy the tissue), abscess (neutrophils contain hydrolytic
enzyme that destroy the tissue), and pancreatitis (pancreatic enzyme digest the pancreas and
liquify; however surrounding fat will have fat necrosis)
7. Describe gangrenous necrosis
- It is coagulative necrosis that resembles mummified tissue (dry gangrene). If infection occurs on
dry gangrene, liquifactive necrosis occurs and is called wet gangrene.
- Characterstic of ischemia of lower limb and GI tract
8.
-
11. What are mechanism by which calcium can deposit in human tissue?
- Dystropic calcification
- Metastatic calcification
12. What is dystropic calcification?
- It's a mechanism by which Ca deposits in a human body (it's abnormal as calcium is not supposed
to just randomly accumulate). Mechanism - when there's a dead tissue, calcium can accumulate
even if serum Ca is normal. Ex - in fat necrosis, in tumor as center of tumor might not get enough
blood supply and die.
13. What is metastatic calcification?
Cellular injury Page 3.3
1.5 Amyloidosis
1. What is amyloid?
Misfolded proteins that accumulates in extracellular space and damages tissue. Amyloid can't be
removed and damaged organs must be transplanted
2. What are characters of amyloid?
Misfolded proteins have B-sheet arrangement
Amyloid are congo red positive (appear apple-green under polarized light)
Chapter 2: Inflammation,
Inflammatory Disorders, and Wound
Healing
1. What is inflammation?
Process by which inflammatory cells, plasma proteins and fluid exit blood vessel to enter
interstitial space
2. Explain acute inflammation
- Characterized by edema and neutrophil in tissue (presence of neutrophils define acute
inflammation)
- Arises in response to infection or necrosis (necrosis is always followed by acute inflammation (HY))
- Goal is to clear pathogen or necrotic debris
- Part of innate immunity (very quick response)
3. How does TLR work?
- Toll like receptors (TLR)- present on cells of innate immune system (macrophage, dendritic cells)
and adaptive immune system. In innate system, TLR recognize PAMP (pathogen associated
molecular patterns)and DAMP (damage associated molecular pattern). Ex - CD14 (aka TLR-4) is a
TLR on macrophage that recognizes lipopolysaccharide (LPS) which is shared by gram negative
bacteria. (HY)
3.1 What chemical is upregulated by TLR?
- NF-KB- NF-KB is a molecular switch that turns on acute inflammation (master regulator for both
innate and adaptive immunity).
- Type 1 interferon (alpha and beta) - inhibit viral replication in cells
Arachidonic acid metabolism
4. Explain production and metabolism of arachidonic acid (AA).
- Phospholipase A2 releases AA from phospholipid cell.
- AA can then be metabolized by cyclooxygenase or 5-lipooxygenase.
5. What are the products of cyclooxygenase pathway and what are their functions.
- Cyclooxygenase pathway produces prostaglandins (PG) - PGI2, PGD2 and PGE2. They increase
vascular permeability and vasodilation. PGE2 also mediates feeeever and pain. Note that
vasodilation happens at arteriole level and vascular permeability at post capillary venule level.
6. What are the products of lipooxygenase pathway and what are their functions
- 5-Lipooxygenase pathway produces leukotrienes (LT). LTB4 attracts and activates neutrophils.
LTC4, LTD4 and LTE4 mediate smooth muscle contraction (vasoconstriction, bronchospasm, and
increased vascular permeability (contraction of pericytes opens up space between endothelial
cells)).
7.
-
Mast cells
7. What are 3 ways that activate mast cells?
- Mast cells are found throughout connective tissue of body and are activated by Inflammation Page 1.1
- Mast cells are found throughout connective tissue of body and are activated by Tissue trauma
Complement proteins C3a and C5a
Cross linking of cell surface IgE by antigen (2 or more IgE on a mast cell binds same antigen)
8. What is acute response of mast cells activation?
- Histamine is released which causes vasodilation and increased vascular permeability.
- Release proteolytic enzymes that kill bacteria or inactivate toxins
9. What is delayed response (after 4-5 hrs) of mast cells activation?
- Mast cells produces arachidonic acid metabolites, particularly leukotrienes. (HY)
Complement
10. What are three pathways of complement activation?
- Classic pathway - C1 protein binds to IgG or IgM which is bound to antigen (pneumonic - GM
makes classic cars)
- Alternative pathway - microbial products directly activate complement
- Mannose binding lectin (MBL) pathway - MBL binds to mannose on microorganisms and activate
complement
11.
-
12.
-
13. What is hageman factor (aka factor 12 in coagulation cascade)? What systems does it activate?
- It's inactive proinflammatory protein produced in liver that's activated by exposure to
subendothelial or tissue collagen, and during severe gram negative sepsis
- Plays imp role in DIC (disseminated intravascular coagulation - pathologic activation of coagulation
cascade) and severe gram negative sepsis (sepsis activates hageman factor which in turn results in
DIC) (HY).
- It activates complement system, coagulation and fibrinolytic system (this results in DIC), and kinin
system
13.1. Explain kinin system.
- Kinin system cleaves high molecular weight kinin to bradykinin. Bradykinin results in vasodilation,
increased vascular permeability and pain). Note - bradykinin system has histamine + pain functions
14. What two molecules mediate pain?
- Prostaglandin E2 (cause feeever and pain)
- Bradykinin
Cardinal signs of inflammation - rubor, calor
15. What causes rubor (redness) and calor (warmth)?
- Vasodialation due to arteriole relaxation mediated by - histamine (primary), bradykinin and PG.
16. What causes tumor (swelling)?
Inflammation Page 1.2
remaining half are stuck to endothelium of lung. Due to loss of adhesion, circulating
neutrophils will increase.
- Recurrent bacterial infection but lack pus formation (HY) - Pus is dead neutorphil in fluid. If
neutrophils can't get into tissue, pus can't form.
9. Where do neutrophils exit blood vessel?
- Post capillary venule.
10. How does phagocytosis occur?
- Neutrophils engulf stuff and make phagosome. Phagosome merges with lysosome to make
phagolysososme. (C3b and IgG are major opsonins)
11. What is Chediak-Higashi syndrome?
- It's an autosomal recessive protein trafficking defect (microtubule railroad tracks in the cells
are defective).
12. What are sign/symptoms of Chediak-Higashi syndrome? (HY)
- It's symptoms are based on impaired microtubule railroad tracks
Immune fingings Neutropenia (impaired cell division so low neutrophils)
Giant granules in leukocytes (newly made granules from golgi won't travel well to
other parts of cell and pile up)
Increased pyogenic infections (phagosome merging with lysosome is impaired, so
immune cells are less efficient at killing pathogens).
Defective primary hemostasis (granules in platelets won't move well)
Albinism (a melanocyte supplies melanin to about 25 keratinocytes. As railroad
transport is defective, it's melanin won't be transported to other keratinocytes)
Peripheral neuropathy - stuff from cell body of neuron won't be transported to axon
endings well.
in CGD.
6. What is nitroblue tetrazolium (NBT) test?
It's a screening test for CGD. In the test, solution turns blue if superoxide radical is present. It tests
if NADPH oxidase is functional.
7. What is clinical significance and NBT test result for people with myloperoxide (MPO) deficiency?
Most MPO patients are asymptomatic but have increased risk for candida infection.
They have normal NBT test.
8. Explain oxygen independent phagocytosis.
It's less effective and occurs via enzyme in secondary granules (ex - lsyozome and major basic
protein).
9. Describe the resolution phase of acute inflammation.
Within 24 hours of resolution of inflammatory stimulus, neutrophils die by apoptosis. It creates
pus. Pus is dead neutrophils in fluid.
10. Describe macrophage phase of acute inflammation.
It peaks 2-3 days after inflammation begins.
When monocytes get into tissue, they are called macrophage. They come to tissue in same steps
as neutrophils.
11. Contrast phagocytosis of macrophage with that of neutrophil.
Phagocytotic killing of macrophage is mainly oxygen independent - via the enzymes in secondary
granules. Lysozyme is main enzyme.
Phagocytotic killing of neutrophil is mainly oxygen dependent.
12. What happens after fluid, neutrophil and macrophage phase of acute inflammation? (HY)
Macrophage are managers which come in to check after 2-3 days of acute inflammation if
neutrophils did a good job at clearing the damage.
If good job is done, macrophage secrete IL-10 and TGF-B. They are anti-inflammatory and induce
healing.
If job is done poorly, macrophage secrete IL-8. It calls additional neutrophils to the site.
If macrophage sense that the offending organism needs to walled off, they create abscess.
Abscess is walled off area of inflammation.
If macrophage sense that neutrophils can't do the job well (ex- neutrophils don't work well in viral
injury), they initiate chronic inflammation by presenting antigen in MHC-2.
Fig - chronic inflammation. Note the absence of multilobed neutrophil. Cell on left is lymphocyte.
Middle cell is plasma cell (nucleus pushed to side, slight perinuclear halo). Cell on right is
macrophage (clock face nucleus).
TH2 cause eosinophil rich inflammation and/or reduce inflammation by secreting IL4, IL5 and IL10.
IL 4 cause class switching to IgG and IgE
IL5 attracts and activates eosionophil, helps in maturation of B cells to plasma cells and cause class
switching to IgA
Il10 (antiinflammatory cytokine) inhibits TH1 phenotype.
8. How do CD8 T cells kill cells?
They secrete perforins that make holes in host cell and secrete granzymes that activate caspase
and induce apoptosis.
They express Fas ligand which binds to Fas receptor on host cell that activates apoptosis.
8.1. How is a self-reactive T-cell killed?
- If there's a self-reactive T-cell, it will bind to MHC-antigen but the second signal won't be present.
It will result in apoptosis or anergy.
B cells
9. How are B cells produced?
Immature B cells are produced in bone marrow. Nave B cells express IgM and IgD.
10. How are 2 ways by which B cells activated? How does isotype switching occur?
Binding of antigen to IgM or IgD activates B cells. Then they become IgM or IgD secreting plasma
cells.
B cells can phagocytose and present antigen to CD4 cells via MHC II. CD40 on B cell can bind to
CD40L on helper T cell providing 2nd signal for activation.
TH2 Helper T cell will secrete IL4 and IL5. IL4 and IL5 help in isotype switching of B cells, somatic
hypermutation (aka affinity maturation), and maturation to plasma cells.
Granulomatous inflammation
11. What is granulomatous inflammation?
Its a type of chronic inflammation. It's defined by presence of epitheloid histiocytes (macrophage
with abundant pink cytoplasm and elongated nuclei) (HY). You may also see multinucleated
macrophages. In healthy tissue, macrophage have clear (aka foamy) cytoplasm.
Granulomas are surrounded by rim of lymphocytes and giant cells.
Only a certain conditions give granuloma so they help to identify diseases.
12. What cause noncaseating granulomas?
Defining feature of noncaseating granuloma is lack of central necrosis.
Causes:
Reaction to foreign material - ex- leaking of breast implants
Sarcoidosis - hallmark of sarcoidosis is production of non-caseating granuloma in multiple
organs (mainly lungs)
Beryllium exposure
Crohn disease - hallmark of Crohn is noncaseating granuloma. (hallmark of UC is crypt
abscess)
Cat scratch disease - give star shaped granuloma in neck
Fig - noncaseating granuloma. Not abundant lymphocytes in periphery that indicates chronic
inflammation. Note multinucleated cell. Presence of nucleus in epitheloid histiocytes means
they are alive - making this noncaseating granuloma.
13. What causes caseating granuloma?
Characteristic of TB and fungal infections. If you see caseating granuloma, do AFB stain to look for
TB, and GMS silver stain to look for fungal infections.
especially viral.
Note pt with celiac disease usually have IgA deficiency.
13. What is Hyper-IgM syndrome?
Pt have too much IgM.
14. What is pathophysiology of Hyper-IgM syndrome? What is presentation?
Patient has mutation in CD40 or CD40 receptor. Due to this, B cells can't activate CD4. In lack of good CD4, cytokines
necessary for Ig class switching is not produced. Pt will have low IgA, IgG, and IgE.
Presentation is recurrent pyogenic infections, especially at mucosal sites. IgG is a opsonin, low amount results in more
formation of pus.
15. What is Wiskott-Aldrich syndrome (WAS)? What causes it? (just memorize)
Pt have thrombocytopenia, eczema, and recurrent infections. Pt have defective humoral and cellular immunity.
Happens due to mutation in WASP (Wiskott-Aldrich syndrome protein) gene and is x-linked.
16. What are the consequence of the following complement deficiencies? (just memorize)
Deficiency from C5-C9 - increased risk of Neisseria infection (HY)
C1 inhibitor deficiency - hereditary angioedema characterized by edema of skin (especially periorbital) and mucosal
Systemic Lupus
4. What happens in Lupus?
- Lupus is a systemic autoimmune disease in which autoantibodies can cause type II (cytotoxic antibody bind and kill cells) or type III hypersensitivity reaction (antigen-antibody complex form
and deposit in tissue causing damage).
5. What are clinical features of lupus?
- Malar 'butterfly rash' upon exposure to sunlight is classic sign
- Diffuse proliferative glomerulonephritis commonly occurs; other nephritic/nephrotic symptoms
can occur too. Renal damage is common cause of death
- Pleuritis and pericarditis, myocarditis, endocarditis
- Libman-Sacks endocarditis - vegetations on both side of valve
- Antibodies against blood result in - anemia, thrombocytopenia or leukopenia. Infections due to
loss of immune system also a common cause of death.
- CNS psychosis due to inflammation of CNS
- Fever and weight loss (fever is sign of inflammation)
- Arthritis
8.
-
What are three common drug that cause lupus? How do we diagnose? How do we treat?
Hydralizine, procainamide and isoniazid
Antihistone antibodies are specific for drug induced lupus
Removal of drug causes remission of disease
9.
-
What is antiphospholipid syndrome associated with SLE? What lab tests does it affect?
Antibodies are made against proteins bound to phospholipid.
Anticardioliptin antibody give false positive syphilis test.
Lupus anticoagulant antibodies give falsely elevated PTT lab study but makes pt hypercoagulable.
16.
What is diffuse type scleroderma? What are clinical presentation? How do you diagnose?
Patient has diffuse skin and early visceral organ involvement.
Esophagus most commonly affected - see solid and liquid dysphagia
Diagnosis made by ANA and anti-DNA topoisomerase I antibody (aka SCL-70 antibody). SCL stands
for scleroderma.
17. What is localized type scleroderma? What are clinical presentation? How do you diagnose?
- Patient has local skin and late visceral organ involvement.
- Presentation (CREST) Calcinosis (calcification of skin), anti-centromere Ab
Raynaud phenomena
Esophageal dysmotility- see solid and liquid dysphagia
Sclerodactyly
Telangiectasis of skin
- Diagnosis made by anti-centromere antibody
Mixed connective tissue disease
18. What is mixed connective tissue disease? How is it diagnosed?
- It is autoimmune tissue damage with mixed features of SLE, scleroderma and polymyositis
(autoimmune damage of proximal muscles). Think of patient with bunch of autoimmune
condition.
- Diagnosis made by presence of antibodies against U1 ribonucleoprotein.
1. What is regeneration?
- It's replacement of damaged tissue with native tissue.
2. What is repair?
- Repair is replacement of damaged tissue with fibrous scar. It occurs when tissue lacks
regenerative capacity or regenerative stem cells are lost.
3. What are 3 different types of tissue based on regeneration capacity?
- Labile tissue - they are continuously regenerating
Intestine - stem cell in mucosal crypt
Skin - stem cell in basal layer (most bottom layer of epidermis)
Bone marrow - hematopoietic stem cells (HSC). (HY - You can't identify HSC by microscope.
Presence of CD34 molecule tells it's HSC)
Lungs - stem cell is type 2 pneumocytes
Skeletal muscle
Neurons
4. What is granulation tissue (different from granuloma which occurs in chronic inflammation)?
What are 3 important cell types in it?
- It's present in early phase of repair. It contains Fibroblasts (deposit type 3 collagen)
Capillaries
Myofibroblast (contract wound)
Fig - granulation tissue showing blood vessels, collagen and fibroblast. Contrast it with granuloma
in chronic inflammation file.
5. What happens when granulation tissue is replaced by scar? What cofactor is needed?
- Collagenase removes type 3 collagen and replaces with type I collagen. It needs zinc as cofactor
(HY).
6.
-
7. How do regeneration and repair happen? What are some key molecules?
- They occur by paracrine signaling via growth factors. Some of them are
Fibroblast growth factor (FGF) - powerfully induces angiogenesis and skeletal development
VEGF - angiogenesis
PDGF - induces growth of endothelium, smooth muscle and fibroblast
TGF alpha - epithelial and fibroblast growth factor
TGF beta - inhibits inflammation, important fibroblast growth factor
8. Contrast wound healing by primary vs secondary intention.
- In primary intention, wound edges are brought together and there's minimum scar formation
- In secondary intention, edges are far away and granulation tissue fills the gap. Due to presence of
myofibroblasts, wound shrinks quite a lot.
9. Explain formation and structure of collagen.
- Collagen is formed as multiple alpha strands inside cells. Multiple alpha strands intertwine to
make procollagen and come outside cell.
- Structure of alpha strand is Gly-X-Y, where X and Y are proline and lycine.
- In extracellular space, multiple procollagen are crosslinked via hydroxyl groups in proline and
lycine to make collagen.
Inflammation Page 7.2
3.1 Neoplasia
1. Define the following
Neoplasia
Desmoplasia - Process by which tumor becomes firm (it is because neoplastic cells induce
fibroblasts within the stroma to form abundant collagen)
Carcinoma in - (aka high-grade dysplasia) - when dysplastic changes involve entire
site
thickness of epithelium (earliest form of epithelial malignancy)
2. What are two ways to determining monoclonality?
- G6PD or androgen receptor isoforms,
- Ig light chain phenotype for lymphomas.
Malignant neoplasia
Remain localized and do not Invade locally and have potential to metastasize (don't
metastasize
have to be already metastasized)
Slow-growing
Rapid growing
Distinct
Infiltrative
Mobile
Benign
Malignant (cancer)
Epithelium
Adenoma
Adenocarcinoma
Papilloma
Papillary carcinoma
Mesenchyme Lipoma
Liposarcoma
Angioma
Angiosarcoma
Chondroma
Chondrosarcoma
Osteoma
Osteosarcoma
Lymphocyte
Melanocyte
Children
1. Cardiovascular disease
1. Accidents
2. Cancer
2. Cancer
Male
1. Prostrate 2. Lung
Female 1. Breast
Cancer by death tolls Male
1. Lung
Female 1. Lung
2. Lung
3. Colorectal
3. Colorectal
2. Prostrate 3. Colorectal
2. Breast
3. Colorectal
- Table excludes squamous cell and basal cell carcinoma of skin - very common and
malignant but rarely metastasize. Detected early and easily treatable.
- Lung cancer doesn't have easy screening test like others. It's usually detected late.
10.
-
Detection
Pap smear
Mammography
- Breast cancer
- Ductal carcinoma in-situ
- Colorectal cancer
- Detect blood in stool (hemoccult test)
Cancer
Remarks
Aflatoxins
Alkylating
agents
- Leukemia
- Lymphoma
- Found in chemotherapy
drugs
Alcohol
Arsenic
Asbestos
Cigarette
Nitrosamine
Napthylaine
Vinyl chloride
- Angiosarcoma of liver
- Occupational exposure
(used to make PVC pipes)
Nickel,
chromium,
beryllium, or
silica
- Lung cancers
- Occupational exposure
Cancer type
EBV
- Nasopharyngeal carcinoma (Classic pt - Chinese male, African person) Neoplasia Page 2.1
EBV
- Nasopharyngeal carcinoma (Classic pt - Chinese male, African person) metastasizes early; classic presentation is neck mass
- Burkitt lymphoma (Classic pt - African kids)
- CNS lymphoma in AIDS
HHV-8
- Hepatocellular carcinoma
HTLV-1
Cancer types
MOA
Ionizing (nuclear
reactor,
radiotherapy)
- AML
- CML
- Papillary thyroid carcinoma
(Cherbonyl kids have lots of
papillary cancer)
Nonionizing (UBV
from sun most
common)
- In xeroderma pigmentosum, restriction endonuclease is bad and pt has high risk of BCC, SCC and
melanoma of skin
5. What is most common cause of ionizing radiation in USA?
- Radon (formed by decay of uranium) - present in soil and accumulates in closed space (basement)
2nd most common cause of lung cancer in USA
Protooncogenes
2. What are protooncogenes and how can they cause cancer?
- Proto-oncogenes are essential for regular cell growth and differentiation
- Mutation produces oncogenes that leads to unregulated cell growth
3.
-
Function of
protooncogene
MOA of cancer
- Astrocytoma
- Platelet derived
growth factor
Overexpression,
autocine loop
ERBB2
(HER2/neu)
- Subset of breast
cancer
Epidermal growth
factor receptor
Amplification
RET
- MEN2A, MEN2B
- Sporadic MTC
Point mutation
KIT
- Gastrointestinal
stromal tumor
Point mutation
GTP-binding protein
Point mutation
ABL
- CML
- Some ALL
Tyrosine kinase
Translocation - t(9,22)
with BCR
- Burkitt lymphoma
Transcription factor
Growth factor
PDGFB
Growth factor
receptors
Signal
Transducers
Nuclear
regulators
C-MYC
C-MYC
- Burkitt lymphoma
Transcription factor
N-MYC
- Neuroblastoma
Transcription factor
Amplification
L-MYC
- Lung carcinoma
(small cell)
Transcription factor
Amplification
CCND1 (cyclin
D1)
Mantle cell
carcinoma
Cyclin
CDK4
Melanoma
Cyclin dependent
kinase
Melanoma
Cell-cycle
regulators
Malignant neoplasia
Slow-growing (years)
- Organized growth
- Uniform nuclei
- Lack of invasion
- Invasion
- No metastatic potential
Fig: Follicular thyroid adenoma (left) - note organized cell growth with colloid in between cells,
uniform nuclei with lots of cytoplasm, minimum mitotic activity. Anaplastic thryoid carcinoma
(right) - disorganized growth (cells look nothing like thyroid), large nuclei:cytoplasm ratio, nuclear
pleomorphism, mitotic figure (very dark nuclei cell).
3. What's the absolute distinguishing feature between benign and malignant tumors?
Neoplasia Page 4.1
3. What's the absolute distinguishing feature between benign and malignant tumors?
- Potential to metastasize (benign tumors never metastasize, malignant tumors can metastasize)
3.5 What are some ways of identifying cell types in tumor?
- Immunohistochemistry
- Serum tumor markers
4. What is intermediate filament? How is immunohistochemistry of intermediate filament helpful in
grouping cancer? (HY)
- Intermediate filament are a type of cytoskeletal protein; different intermediate filament are
present in different cell types. - Immunohistochemistry of intermediate filament helps in identifying cell types in tumor.
Cell type
Epithelium
Keratin
Desmin
Neuroglia
GFAP
Neurons
Neurofilament
Immunohistochemistry
molecule
Prostrate
Breast epithelium
ER (estrogen receptor)
Thyroglobulin
Chromogranin (HY)
Melanoma
S-100
What does tumor grading of well differentiated and poorly differentiated mean?
Well differentiated - tumor resembles parent tissue - good prognosis
Poorly differentiated - tumor doesn't resemble parent tissue - poor prognosis
Look at cellular architecture and nuclear morphology to classify differentiation
8.
-
CMAP summary
Quantitative disorders
8. What is idiopathic thrombocytopenic purpura (ITP)?
- Most common cause of thrombocytopenia in kids and adults. Autoimmune production of IgG
against platelet antigens (ex- GP IIB/IIIA)
- Antibodies are made in spleen, and tagged platelets are phagocytosed by spleen macrophages.
Low platelets cause purpura (bleeding spots in skin)
Corticosteroids
Kids respond well to corticosteroids, adults may show early response but
usually relapse
Hemostasis Page 2.2
usually relapse
IVIG (IV
immunoglobulins)
Used for symptomatic bleeding. spleen macrophages will eat them instead
of immunoglobulins bound to platelets.
Splenectomy for
severe cases
Fig - schistocyte - the two pointy things at the end is classic appearance of cut RBC
12. What is thrombotic thrombocytopenic purpura?
- There are lots of thrombus in blood vessels that result in low platelet (thrombocytopenia) and
purpura (skin bleeding due to low platelet).
13. What causes thrombotic thrombocytopenic purpura (HY)?
- Caused due to deficiency ADAMTS13 enzyme. ADAMTS13 normally cleaves VWF multimers into
smaller monomers for eventual degradation. Bad ADAMTS13 = too much VWF = more platelet
adhesion resulting in microthrombi.
- Low ADAMTS13 is usually due to acquired autoantibody and most commonly seen in adult
females
13. What is hemolytic uremic syndrome (HUS)?
- Platelet microthrombi causes hemolysis. This mainly occurs in kidney leading to uremia and in
brain.
14. What causes HUS (HY)?
- Classically seen in children with E Coli 015:H7 dysentery - results from exposure to undercooked
beef. Dysentery = bloody diarrhea
- E Coli verotoxin damages endothelial cells in kidney and also reduces ADAMTS13 resulting platelet
microthrombi
15. What are clinical findings of TTP and HUS?
- Skin and mucosal bleeding
- Microangiopathic hemolytic anaemia
Hemostasis Page 2.3
- No agglutination
- Yes agglutination
20. What is treatment for vWF disease? What's the mechanism? (HY)
Desmopressin - they increase vWF release from Weibel Palade bodies of endothelial cells (primary
site of VWF storage, another substance in Weibel palade bodies = P selectin).
21. What is the function of vit K in coagulation cascade? How does coumadin work?(HY)
They are necessary for gamma carboxylation of factor 2,7,9,10, factor c, factor s
Vit K is activated by epoxide reductase in liver (coumadin blocks epoxide reductase and prevents
activation of vit K)
22. What causes vitamin K deficiency?
Vit K is generated by bacteria in our gut. So deficient pt either take less vit K or have abnormal
bacteria.
Newborns (their gut is not well inhabited by bacteria) - newborns are prophylactically given
vit K.
Long term antibiotic therapy
Hemostasis Page 3.2
Hyperactive plasmin
7. How is plasmin formed? What are its functions? How is it inactivated?
- Normally, plasminogen is converted to plasmin by tPA (tissue plasminogen activator).
- Plasmin's function dissolves the cross-linked fibrin,
cleaves and destroys fibrinogen
destroys coagulation factors,
blocks platelet aggregation.
- Plasmin is inactivated by alpha-2-antiplasmin
8. What happens if plasmin is hyperactive? What are some conditions that give rise to hyperactive
plasmin?
- It prevents clot formation due to destruction of coagulation factors and fibrinogen
- Radical prostatectomy - releases urokinase that activates plasmin
- Cirrhosis of liver - it causes reduction if production of alpha 2 antiplasmin
9. What is clinical presentation of hyperactive plasmin?
- Presentation is same as DIC
10.
-
What are lab findings in hyperactive plasmin? Contrast it with DIC lab findings.
Increased PT and PTT
Increased bleeding time with normal platelet count (DIC has low platelet count)
Increased fibrinogen split products without D-dimers (low D-dimer as there's no fibrin to cleave)
4.4 Thrombosis
Fig - lines of Zahn (the alternate layer of RBC and fibrosis - marked by R & f) is characteristic
of thrombosis
3. What are 3 main risk factor of thrombosis (virchow's triad)? Give examples of each.
- Disruption of blood flow - stasis or turbulence of flow. Ex - immobilization, cardiac wall
dysfunction, MI, aneurism (there's turbulence in an aneurism)
- Endothelial damage. Ex - artherosclerosis, vasculitis, high level of homocysteine (vit B12 or folate
deficiency or homocystinurea)
- Hypercoagulable state (excess procoagulant or defective anticoagulant)
4. How does intact endothelium prevents thrombosis?
- It blocks exposure of tissue collagen and tissue factors from coagulation factors and platelets
- It makes prostaglandin I2 (prostacyclin) that blocks platelet aggregation. It's function is opposite of
thromboxane A2 made by platelets.
- It secretes heparin like molecules (HLM). HLM activate antithrombin 3.
- It's makes t-PA that activates plasmin.
- It makes thrombomodulin. Thrombomodulin enhances activation of protein C by thrombin.
Protein C is inhibitor of coagulation factors - 5 and 8.
5. Why does vit B12 or folate deficiency causes high level of homocysteine?
- Because vit B12 and folate are needed to convert homocysteine to methionine.
- MOA - Folate becomes tetrahydroflorate in body. It gets activated by giving its methyl group to vit
B12. It then participates in DNA synthesis. Vit B12 gives the methyl group to homocysteine and
homocysteine becomes methionine.
- High level of homocysteine is damaging to the endothelium
Homocystinurea
6. What is homocystinurea (aka cystathione beta synthase (CBS) deficiency)?
- Disease with high level of homocystine caused due to deficiency in Cystathione beta synthase
enzyme. CBS converts homocystine to cystathionine.
Hemostasis Page 5.1
7.
-
4.5 Embolism
1. What is embolism?
- It's a intravascular mass that travels and occludes downstream vessels.
- Thromboembolism is most common type (>95%) - embolus will have line of Zahn?.
2. What is atherosclerotic embolus?
- It's an atherosclerotic plaque that dislodges. It's characterized by presence of cholesterol
clefts in embolus.
Fig - presence of cholesterol crystal (three white columns) indicates that this embolus is
artherosclerotic and not thrombotic.
3. When does fat embolus occur? What is its clinical presentation?
- Associated with bone fractures - while the fracture is present or shortly after repair
- The embolus mostly travels to lung so classic signs are dyspnea and petechiae on skin
overlying the chest
- Presents with 'bends and choke' - respiratory problem and joint, muscle pain due to embolus
in lungs, muscle and joint.
5. What is Caisson disease (aka diver's disease)?
- Chronic form of gas embolus disease. Presents with multifocal ischemic necrosis of bone.
6. What is amniotic fluid embolus?
- Amniotic fluid enters maternal circulation usually during labor and cause embolus.
- Classic presentation is SOB, neurologic symptoms due to embolus in lung and brain. Pt also
might get DIC (disseminated intravascular coagulation disease- pathologic activation of
coagulation cascade).
7. Why do patient with amniotic fluid embolus at high risk for DIC?
- Because amniotic fluid is filled with tissue thromboplastin which activates factor 7 that leads
to activation of extrinsic coagulation cascade.
8. What is characteristic finding in amniotic fluid embolus?
- Embolus will have squamous cell and keratin debris from baby's skin.
Fig - amniotic fluid embolus in a blood vessel near alveoli. Note presence of keratin debris
(squiggly lines) inside the blood vessel.
9. What is most common cause of pulmonary embolism (PE). What is its most common clinical
presentation?
- Most common due to thromembolus from DVT.
- Most PE are clinically silent as lung has dual supply from pulmonary artery and bronchial
artery. Also, the embolus are usually small and self-resolve.
9. What increases chance of pulmonary infraction from PE? What is the gross feature of
infraction?
- Obstruction of large or medium sized artery
- Pre-existing cardiopulmonary compromise
- Hemorrhagic wedge shaped infraction (hemorrhagic because tissue in lung is loosely
organized and reperfusion occurs from the dual arterial supply).
10.
-
CMAP summary
5.1 Anemia
9:23 PM
Fig: microcytic anemia. Normal RBC size is equal to size of nucleus of lymphocyte. Notice that multiple
RBC are smaller than that. Also notice variability in size of RBC and increased pallor in center of RBC
Fe deficiency anemia
4. What is epidemiology Fe deficiency anemia.
- Fe deficiency is the most common nutritional deficiency in the world making this the most common type
of anemia (1/3rd of world is deficient in Fe)
5. Describe digestion and storage of Fe (HY).
- Fe is absorbed in duodenum (HY). Protein called FERROPORTEIN plays a key role in Fe transport from
lumen to enterocyte to blood.
- TRANSFERRIN transports iron in blood and takes it to liver and bone marrow macrophage for storage
- Stored intracellular iron is bound to FERRITIN
- There is no real way to get rid of Iron from body. So absorption by enterocytes is regulated. (some lost
during skin sloughing off and menstruation)
- Iron is always bound to something because free Fe generates free radical by fenten reaction.
6. What are lab measurement for Fe in body?
- Serum Fe measures Fe in blood (most of it is bound to transferretin)
- TIBC (total iron binding capacity) tells total transferritin in blood. Normally, 1 in every 3 transferritin in
blood is bound to Fe.
- % saturation % saturation of transferritin by Fe
- Serum ferritin indication of how much Fe is in storage sites
- When ferritin, TIBC and vice versa(liver makes more TIBC to search for more Fe)
7. What are some etiologies of Fe deficiency anemia?
- Malabsorption
o Celiac
o Gastrectomy (HY) Fe 2+ is absorbed easily (Fe 2 goes INTO the body). Acidic environment
promotes Fe 2 conformation. When stomach is resected, due to lost acidity, more Fe will be in 3+
and Fe wont be absorbed well.
RBC disorders Page 3.2
9.
-
- Poikilocytosis (variable shapes), anisocytosis (variable size), cigeratte shaped RBC (classic finding), tear
drop RBC
- Microcytic anemia (note RBC smaller than lymphocyte nucleus)
13. What is treatment of Fe deficiency anemia?
- Iron supplement Ferrous sulfate
- Rule out any risk factors (ex if old people, rule out colon carcinoma)
14. What is Plummer-Vinson syndrome?
- Iron deficiency anemia with esophageal web and atrophic glossitis (smooth tongue due to lack of white
papillae- beefy red appearance)
Anemia of chronic
disease
Transferrin/TIB
C
Serum Fe
Ferretin
Fig: ringed sideroblasts seen in bone marrow biopsy (purssian blue stain marks Fe)
8. What are steps of heme synthesis?
Acquired
10. What are clinical features of lead poisoning leading to sideroblastic anemia?
- Pt at old house with chipped paint at high risk
- Mnemonic LEAD:
o L - Lead lines on gingivae and metaphyses of long bones (aka Burton lines)
o E - Erythrocyte basophilic stippling and encephalopathy (lead inhibits rRNA degradation causing
RBCs to retain aggregates of rRNA seen as basophilic stippling)
o A - sideroblastic Anemia, Abdominal colic
o D - Dimercaprol and EDTA for treatment; Wrist and foot Drop
o Succimer used for chelation in kids - sucks to be kid that eats lead
Fig: From right to left - basophilic stippling; Burton lines on gum; metaphysis
11. What are lab findings in sideroblastic anemia? What's its treatment?
- Lab findings based on Fe overload as they cant attach to portoprophyrin
- As Fe increase in erythroblast, cells die due to free radical produced by Fenten reaction. Fe leaks out and
is taken by macrophage.
- ferritin, TIBC
- serum Fe, % saturation
- Very similar lab findings as hemochromatosis
- Treatment:
o Pyrodoxine (B6 - cofactor for ALAS)
bsubunit
Developmental
stage
HbF
HbA
Adult
HbA2
What causes alpha thalassemia? What chromosome is alpha gene located in?
Alpha thalassemia is caused due to gene deletion of alpha chain of hemoglobin.
Normally, 4 alpha alleles are present on chromosome 16 (2 allele per chromosome)
'a in alpha looks like d (deletion); if you rotate b in beta, you get m (mutation).
4 alpha allele
deleted - Hb Bart
Hydrops fetalis
- Severe anemia
- Lethal in utero
(hydrops
fetalis)
formed, B chain
tetramers(aka
tetramers (aka HbH) are Hb Barts) are
formed (4 B combine
formed
due to bad A)
- HbH can be seen on
electrophoresis
- Hb Barts seen
on
electrophoresis
6. What causes beta thalassemia? What chromosome is beta gene located in?
- Beta thalassemia is caused due to mutation of beta chain of hemoglobin. Mutations result in absent (aka
B0) or diminished (aka B+) production of B-globin chain.
- Normally, 2 beta alleles are present on chromosome 11 (1 allele per chromosome)
7. What are subtypes of beta thalassemia?
B/B+
B0/B0
- MOA- due to reduced hemoglobin in edge of RBC, the membrane in center gets floppy and some
hemoglobin comes to stay there.
9.
-
Fig: chipmunk face (left) and crewcut appearance (right) seen in massive erythroid hyperplasia
10. What is treatment of beta thalassemia major? What's it's complication?
- Treatment is chronic blood transfusion; splenectomy for swollen spleen and iron chelation to prevent
secondary hemochromatosis
Megaloblastic anemia
Vit B12 and Folate deficiency
2. Describe relationship between folate and Vit B12.
- Folate comes to body as methylated tetrahydrofolate (M-THF).
- THF is the active form. M-THF donates it's methyl group to Vit B12. Vit B12 then gives methyl
group to homocysteine. Homocysteine now becomes methionine.
Fig: hypersegmented neutrophils with large RBC (aka macroovalocyte) on the left- classic
finding in megaloblastic anemia
4. What is difference between megaloblastic anemia and macrocytic anemia that's not
megaloblastic?
- In macrocytic anemia that's not megaloblastic, hypersegmented neutrophils and megaloblastic
changes (ex - large intestinal epithelial cells) won't be seen. Large RBC will be seen.
5. Compare dietary information of folate and vit B12.
Folate
Vit B12
Food
Absorption
Jejunum
Ileum
Deficiency
Causes of
deficiency
6. Compare clinical and lab findings of folate and Vit B12 deficiency.
RBC disorders Page 6.2
6. Compare clinical and lab findings of folate and Vit B12 deficiency.
Folate deficiency
- Glossitis (inflammation of
- Glossitis
tongue - due to less turnover of
tongue cells)
- Low serum folate
7. What are two important reactions that Vit B12 participate in?
- DNA precursor synthesis (with folate)
- Conversion of methylmalonic acid to succinyl Co. A
Orotic aciduria
Defn
Defn
Causes - Alcoholism
- Liver disease
- Hypothyroidism
- Reticulocytosis
3. How can reticulocyte be falsely elevated in anemia? How is reticulocyte count corrected?
Reticulocytes are measured as percent of total RBC. In anemia, total RBC goes down. It will
elevating the percent of reticulocytes.
Its corrected by multiplying reticulocyte percent x hematocrit/45.
Total RBC
Total
Reticulocyte
% of
reticulocyte
Normal pt 100
(given)
2 (given)
2%
Anemic
pt
2(given)
4%
50 (given)
HCT
Corrected
reticulocyte
23 (given)
4 x 23/50 = 2%
In this example, if we only look at % of reticulocyte, it looks as if bone marrow is normal. But from
corrected reticulocyte, we know that anemic pts bone marrow is not producing adequate
reticulocytes.
4. How can reticulocyte count differentiate cause of anemia?
If corrected reticulocyte >3%
Hereditary spherocytosis
1. What is hereditary spherocytosis? What are the mutations?
- In the disease, tethering proteins that attach RBC cytoskeleton to RBC membrane are mutated.
RBC membrane blebs and are lost over time. RBC becomes more spherical.
- Most common mutations are in proteins - ankyrin, spectrin, or band 3.
2.
-
Fig: spherocytes with high RDW (note variability in RBC sizes and loss of central pallor)
3. What is one feared complication?
- Increased risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
4. How is diagnosis of hereditary spherocytosis made?
- Osmotic fragility test - cells bursts in hypotonic solution very easily because cell doesn't have
much membrane to expand out
5. What's it's treatment?
- Splenectomy (having spherocytes isn't problem, spleen eating them is problem)
- Anemia resolves but spherocytes persist and Howell-Jolly bodies are seen
6. What's Howell-Jolly bodies?
- Some RBC's are impefectly made with little nucleus or nuclear material left. It's job of spleen to
take them out or kill the defective RBC. Howell-Jolly bodies are RBC with nuclear remnant. It
indicates splenic dysfunction
Hemoglobin composition
Trait (one mutated and one normal B chain) 55% HbA, 43% HbS, 2% HbA2
HbS sickle cell hemoglobin (in 22 protein, both copies of are mutated)
2. What is pathogenesis of sickle cell anemia?
HbS polymerizes when deoxygenated (reversible). The polymers accumulate into needle shaped
structures and make RBC sickle cell.
Sickling and de-sickling damages membrane leading to both intravascular and extravascular
hemolysis (spleen eats damaged RBC); sickled RBC cause vaso-occlusion; massive erythroid
hyperplasia to replace RBC.
Sickling increases with hypoxemia, dehydration and acidosis.
HbF protects against sickling. Kids protected for first few months of life.
Hemoglobinemia, hemoglobinuria
Hemosiderinuria after few days
Target cells - hemoglobin leaks out due to membrane damage and extra membrane
produces target cells
Massive erythroid hyperplasia (to compensate hemolysis and anemia):
Hematopoiesis in skull and facial bones (crewcut on X-ray and chipmunk face)
Extramedullary hematopoiesis (in liver, giving hepatomegaly - pt don't have spleen so don't
get splenomegaly)
Risk of aplastic crisis with parvo B19 infection
Fig: chipmunk face (left) and crewcut appearance (right) seen in massive erythroid
hyperplasia
Extensive sickling leads to vaso-occlusion
5.
What are some physical findings in sickle cell disease due to vaso-occlusion?
All findings based on infraction
Dactylitis due to vasoocclusive infaracts in bones common in infants
Autosplenectomy shrunken, fibrotic and calcified spleen
Increased risk of encapsulated organism infection (staph aureus, strep pneumo,
haemophilus influenza)
Salmonella paratyphi osteomyelitis (encapsulated) - most common cause of osteomyelitis
is staph aureus; in sickle cell, it's salmonella.
Howel-Jolly bodies on blood smear - nucleated RBC
Acute chest syndrome (vaso-occlusion of pulmonary microcirculation)
Often precipitated by pneumonia
Presents with chest pain, SOB, lung infiltrates
Pain crisis
Renal papillary necrosis presents as gross hematuria and proteinuria
Fig: vaso-occlusive complications of sickle cell disease - from left to right - autosplenectomy - small
calcified spleen; renal papillary necrosis; dactilytis; Howel-Jolly bodies
6. Whats the most common cause of death in sickle cell patients?
Kids
Adults
Adults
Hemoglobin C
1. What is hemoglobin C?
- Hemoglobin C is formed due to mutation in Beta chain of hemoglobin (autosomal recessive).
- Glutamic acid is changed to lysine (lyCne for hemoglobin C) - think Gingiva - Glutamic acid to
lyCine as gingiva is C shaped)
- Less common than sickle cell disease
2. What is presentation of hemoglobin C?
- Mild anemia due to predominant extravascular hemolysis
- HbC crystals on blood smear (HY)
Blood
smear
- DAF (decay accelerating factor) and MIRL (membrane inhibitor of reactive lysis) are present in
RBC, WBC and platelets. They block complement fixation in RBC. DAF decays C3 convertase.
- Protein called GPI (glycosylphophatidylinositol) anchors MIRL and DAF to cells.
2. What causes paroxysmal nocturnal hemoglobinuria?
- It's acquired (not congenital mutation) defect in myeloid stem cell so that GPI is absent in myeloid
stem cells. Complement fixation lyses RBC, WBC and platelets
3. What is presentation of PNH?
- Symptoms are seen paroxysmally at night because breathing becomes swallow and mild acidosis
activates complement at night.
- Dark urine early morning
- Hemoglobinura, hemoglobinemia
- Hemosiderinura seen few days after hemolysis (after tubular cells slough off)
- Thrombosis - due to release of clotting factors from lysed platelets
4. What is main cause of death in PNH?
- Thrombosis of hepatic, portal or cerebral veins - due to release of clotting factors from lysed
platelets
5. What are complications of PNH?
- Fe deficiency anemia (due to chronic loss of Hb in urine)
- Acute myeloid leukemia (10% of patients)
6. How is diagnosis of PNH made?
- Screening - Sucrose test
- Confirmatory test - acidified serum test or flow cytometry to test lack DAF (aka CD55) on RBC
Glucose-6-Phosphatase dehydrogenase (G6PD) deficiency - aka favism
1. What is G6PD deficiency? What's it's pathophysiology
- X linked recessive disorder (see in men) that results in low half-life of G6PD.
- G6PD is first enzyme in pentose phosphate pathway and is required to make NADPH. NADPH is
important to reduce oxidative stress.
- G6PD deficiency presents as increased oxidative stress including hemolytic anemia.
2. What are two major variants of G6PD deficiency?
African variant
Mediterranean variant
5.
-
- Hemolysis is usually extravascular - tagged RBC are eaten - Hemolysis is usually extravasculartagged RBC are eaten
- Warm agglutination - IgG binds to RBC in warm temp
(central parts of body).
- Splenic macrophage phagocytose tagged RBC leading to
formation of spherocytes (when RBC are eaten only
halfway, remaining RBC makes sphere)
- Associated with:
- Lupus - pt have anti-blood Ab
- Associated with:
Mycoplasma pneumoniae
RBC disorders Page 9.2
Mycoplasma pneumoniae
(cold agglutination test)
infectious mononucleosis (+ve
haterophile agglutination - Ab
made against sheep blood)
CLL
- Treatment
Stop offending drug
Steroids
IVIG (distract spleen)
Splenectomy - spleen is the one that eats RBC
3. How do you diagnose IHA?
Direct coombs test
Fig - schistocytes (helmet cells) - has mostly two acute angle and loss of about 50% of RBC;
contrast bite cells that have usually >2 acute angles and almost entire volume of RBC is present.
Malaria
1. How does malaria cause anemia?
- Plasmodium infects and replicates in RBC. RBC ruptures as merozoites (a stage in their lifecycle)
RBC disorders Page 9.3
- Plasmodium infects and replicates in RBC. RBC ruptures as merozoites (a stage in their lifecycle)
are released
- Spleen also consumes infected RBC causing some extravascular hemolysis
Erythroblastosis fetalis
Defn
- Maternal IgG crossing placenta and attacking fetal RBC (ex - Rh -ve mother carrying
two consecutive Rh +ve babies)
Present - See extramedullary hematopoiesis (ex - in liver) because RBC are damaged
4.
-
Aplastic anemia
1. What is aplastic anemia?
- Aplastic anemia is damage to hematopoietic stem cell resulting in pancytopenia (anemia,
leukopenia, thrombocytopenia)
2. What are etiologies of aplastic anemia?
- Etiologies:
Drugs or chemicals, radiation
Viral infection - parvo B19, HIV, EBV, HCV
Autoimmune damage
Fanconi anemia (inherited DNA repair defect that causes bone marrow failure) - high risk of
leukemia later
3. What are biopsy finding in aplastic anemia?
- Empty fatty marrow
Fig: Aplastic anemia (left) vs normal bone marrow on right. Note the depletion of marrow and
replacement by fat globules on left.
4.
-
Myelophthisic process
1. What are melophthisic process?
- Pathologic processes that replace bone marrow (ex - cancer)
- Hematopoiesis is impaired resulting in pancytopenia
1. Spleen
- PALS (periarteriolar lymphatic sheath) - has T cells (drink tea with pals) - in white pulp
- Germinal center - has B cells - in white pulp
CMAP summary
1.
2.
3.
4.
5.
6.
2.
-
Leukopenia
1. List the differences between neutropenia and lymphopenia.
Neutropenia
Lymphopenia
Causes:
- Drug toxicity- Chemotherapy - Damage
stem cell and decreased production of
WBC, specially neutrophil
- Severe infection- Neutrophils move to
tissue
- Lupus
Causes:
- Immunodeficiency - HIV, DiGeorge syndrome
- High cortisol - Induces apoptosis of lymphocytes
- Autoimmune destruction - Lupus
- Whole body radiation - Lymphocytes are highly
sensitive to radiation; lyphopenia is earliest change to
emerge after whole body radiation
Neutrophilic
leukocytosis
- Bacterial infection or tissue necrosis (also see left shift which have decreased Fc receptors
(CD16)
- High cortisol state - impairs neutrophil adhesion; marginated pool is released to blood
(marginated pool - leukocytes that are attached to vessel wall and hang there like bats)
Monocytosis
Eosinophila
Basophilia
Basophilia
Lymphocytic
leukocytosis
- Viral infection
- Bordetella pertussis (whopping cough)- (exception because bacteria usually increase
neutrophil)
Infectious mononucleosis
1. What causes mono?
- EBV (most common), CMV (less common)
2. What's presentation of EBV infection?
- Mono has classic triad of lymphadenopathy, fever and exudative pharyngitis
- Other:
T cell hyperplasia
Lymphadenopathy due to hyperplasia in paracortex (location IMP to know)
Splenomegaly due to hyperplasia in periarterial lymphatic sheath (PALS)
Hepatitis
3. Describe the screening test for mono (monospot test)?
- Test detects haterophile antibodies (haterophile = loves others) - detects IgM Ab that cross-react with horse or
sheep RBC
- Test turns positive after 1 week of infection
4. What are two cases where person has mono but monospot test is negative?
- Mono is caused by CMV (only EBV mono will have positive monospot test)
- Test is done within 1 week of infection
5. What's definitive diagnosis for EBV infection?
- Serologic test for EBV viral capsid Ag.
6.
-
- Types:
Acute lymphoblastic leukemia (ALL) - presence of >20% lymphoblast stem cell
Acute myeloid leukemia (LML) - presence of >20% myeloid stem cell
2. What is presentation and clinical findings in acute leukemia?
- Normal hematopoiesis is disturbed:
Anemia (tired)
Thrombocytopenia (bleeding)
Neutropenia (infection)
- Note that WBC count is high due to presence of lots of blasts in blood
- Blast cell appear as large immature cells with punched out nucleoli.
Fig: blast cells with punched out nucleolus (as if punched via punching machine) - notice lots of
them (gives high WBC count)
Acute lymphoblastic leukemia
1. How do you distinguish if acute leukemia is from myeloblast of lymphoblast?
Acute lymphoblatsic leukemia +ve nuclear staining for TdT (a DNA polymerase)
Pt popn
Prognosis
- t(12;21) has better prognosis (girl with 1 wand and tutu looking at her reflection)
- Excellent response to chemotherapy - chemo girl kissing on the last figure
- Give prophylactic chemo to testes and CNS - bottom left figure guy hitting enemy
on head and testes
Markers
Cause
Acute
megakaryoblastic
leukemia (MPO ve)
Myelodysplastic syndrome
7. What is myelodysplastic syndrome?
- Dysplasia of myeloid stem cells. It increases risk of AML.
- Presents as
>3% but <20% blasts (if it's >20%, it's acute leukemia)
abnormal maturation of cells and increased blasts because cells can't fully differentiateWBC disorders Page 4.3
abnormal maturation of cells and increased blasts because cells can't fully differentiatethat's why increased risk of AML
Most pt die from infection or bleeding (some progress to AML)
Cytopenia and hypercellular bone marrow (cells are stuck in bone marrow and not going
out)
- Ex - Pseudo-Pegler-Huet anomaly - neutrophils with bilobed nuclei typically seen after
chemotherapy
1.
-
Remarks
CaLL - CLL
Epid
resistant acid
phosphatase) and
hairy cytoplasm) hairs trap; mature
people are hairy
Picmonic:
1.
-
Dominant cell
Mutation
Chronic myeloid
leukemia (CML)
Granulocytes (neutrophil,
eosinophil, basophil); increased
basophil (HY)
Polycythemia vera
(PV)
RBC
Essential
thrombocythemia
(ET)
Platelets
Myelofibrosis
Megakaryocytes
4. How do you distinguish CML from lukemoid reaction (reactive neutrophilic leukocytosis)?
CML
Lukemoid reaction
No increase in basophil
t(9;22) present
t(9;22) absent
CML
Camel
Fig: polycythemia presentation - from left to right: dural sinus thrombosis, Erythromelalgia, facial
plethora, itching, hepatosplenomegaly, gout
2.
-
Reactive polycythemia
Myelofibrosis
Presentation
Presentation:
- increased risk of thrombosis and/or
- Increased risk of thrombosis and/or bleeding,
bleeding (low platelet due to too
infection
much thrombosis)
- Hepatosplenomegaly - they will produce blood
cells as marrow is fibrosed (MOST COMMON
- Splenomegaly - spleen has to eat
too much platelets
CAUSE OF SPLENOMEGALY IN PT >55 YEAR
- Rarely progress to marrow fibrosis
OLD)
or acute lukemia
- Marrow fibrosis (due to PDGF production from
megakaryocytes) will impinge on bone and
- Rare risk for hyperuricemia or gout
WBC disorders Page 6.4
- Diagnosis:
Tear drop RBC
Bone marrow tap will be dry; see fibrosis in
biopsy
- Treatment:
Asprin for low risk pt to prevent
clot
Hydroxyurea , interferon alpha to
reduce megakaryocyte formation
Plateletpheresis - take excess
platelet from circulation in
emergency condition
- Treatment:
Stem cell transplant - replace fibrosis
Transfusion to give blood cells thats missing
1. What is lymphoma?
- Neoplastic proliferaion of lymphoid cells that makes a mass; may arise in lymph node or extranodal tissue.
Non-Hodgkin lymphoma
Frequency
40%
60%
Malignant cells
Reed-Sternberg cells (owl eye cells) - B cells induce inflammation and fibrosis
Mass
composition
Clinical
- Painless lymphadenopathy
- B symptoms
- Bimodal: classically seen in young adult
and >55 yrs
- Painless lymphadenopathy
- Classically seen in late adults
Spread
Staging
Guides therapy
Radiation mainstray treatment
Limited importance
Occurs
Association
EBV
Characters
Nodular sclerosis
Fig: band of fibrosis (left), lacunar cells (a variant of Reed sternberg cells - right)
Mixed cellularity
Lymphocyte rich
Remarks
WBC disorders Page 8.2
NH lymphoma Cause
Remarks
Follicular
lymphoma
Mantle cell
lymphoma
Burkitt
lymphoma
Diffuse large
B-cell
lymphoma
- Arise sporadically or transformation of low grade lymphoma (exfollicular lymphoma, chronic lymphocytic leukemia)
Multiple myeloma
1. What is multiple myeloma? What is molecular mechanism?
- MM is malignant proliferation of plasma cells in bone marrow. It's most common primary
malignancy of bone.
- Serum IL-6 (aka RANK-L) may be increased that induces plasma cell growth and Ig production.
2. What are clinical features of MM?
Bone pain with
hypercalcemia
Elevated serum protein (M - Classically due too much IgG (55% of cases) or IgA (25%)
spike present in serum
production
protein electrophoresis SPEP)
Rouleaux formation on
blood smear
(rouleau = cylindrical
packet of coins)
Anemia
Primary AL amyloidosis
Generalized lymphadenopathy
- Treatment:
Plasmapheresis to remove IgM from serum
Clinical presentations
Malignant
proliferation of
Langerhans cells
Eosinophilic granuloma
Benign
proliferation of
Langerhans cells
in bone
Hand-Schuller-Christian disease
Malignant
proliferation of
Langerhans cells
Exopthalmos
- Classic features:
If you see person's name, it's malignant and you see rash
if disease has 2 person's name, pt is <2 year old
If disease has 3 person's name, pt is >3 years
Vasculitis
Temporal Arteritis
Polyarteritis nodosa
Wegner granulomatosis
Microscopic polyangiitis
Churg-Strauss
Henoch-Schonlein
Granulomatous vasculitis
Vessel is affected segmentally. Therefore, take a long segment out for biopsy. Negative biopsy doesn't
rule out disease.
Fig - temporal arteritis biopsy. M is the media, I is the intima, F is the area of fibrosis between media and
intima that has narrowed the lumen, circle above M shows giant multinucleated cells, circle left of F
shows inflammation.
7. What is treatment of temporal arteritis (HY)?
Corticosteroid. Treat soon because of high risk of blindness due to involvement of ophthalmic artery.
8. Contrast symptoms of temporal arteritis with Takayasu arteritis (aka pulseless disease) - a type of large
vessel arteritis?
Takayasu arteritis is same as temporal arteritis with a couple of exceptions Affects mainly adults <50. Classic pt is young asian female
Affects aortic arch at branch point instead of branches of carotid artery
Visual and neurologic symptoms
Weak or absent pulse in upper extremity (therefore disease called pulseless disease)
ESR is elevated, vasculitis is granulomatous
Treat with corticosteroids
Medium vessel arteritis
9. What is polyarteritis nodosa (a type of medium vessel arteritis)?
Necrotizing vasculitis that affects vessels in many organs but spares the lungs
10. What is clinical presentation of polyarteritis nodosa? What chemical is it associated with?
Classic pt is young adults
Symptoms depend on vessel involved Renal artery involvement cause hypertension
Mesenteric arteries - abdominal pain with melena
CNS arteries - neurologic disturbances
ESkin lesions
Associated with serum HBsAG (hepatitis B surface antigen)
11. Correlate pathophysiology of polyarteritis nodosa with imaging.
Vascutis, HTN Page 1.2
Fig - the red marking showing fibrinoid necrosis seen in polyarteritis nodosa.
Coronary artery
Complication thrombosis with MI (3 year old kid with MI) - due to endothelial damage and exposure of collagen
and tissue factor
aneurysm with rupture
((imagine a kid driving kawasaki bike with his hands and legs, his HR goes up - so the disease affects heart
mainly)
13. What is treatment of Kawasaki disease?
Asprin to prevent thrombosis (antiplatelet drug - prevents formation of thromboxane A2)
IVIG (intravenous immunoglobulins)
Disease is self-limited
14. Why don't you give asprin to kids with viral disease?
Because they can get Rye syndrome - encephalopathy and massive liver necrosis.
15. What is Buerger disease (medium vessel vasculitis)? How do you treat it?
It's necrotizing vasculitis involving digits. Presents with ulceration, gangrene, and autoamputation of
fingers and toes.
Disease associated with Raynaud phenomenon - pale to blue to red color change in digits due to
exposure to cold. Pale and blue color are due to vasospasm; red is due to return of circulation.
Disease is associated with smoking - treatment is smoking cessation (HY)
Small vessel vasculitis (wegner granulomatosis, microscopic polyangitis, chug-strauss, and Henoch Schonlein)
The first 3 of these disease can lead to RPGN.
Henoch Schonlein has IgA deposition and can lead to IgA nephropathy
Wegner Granulomatosis
Microscopic polyangiitis
Necrotizing vasculitis
Necrotizing vasculitis
Granulomas absent
C-ANCA positive
P-ANCA positive
Churg-Strauss
Henoch-Schonlein purpura
Necrotizing vasculitis
P-ANCA positive
Affects multiple organs including lung and GI involvement can cause GI pain bleeding
heart
Treat by steroids if necessary. Disease self limited.
Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys. (think weCner's diseaseand imagine a 'C' in a human body passing through nasopharynx, lungs and kidneys).
17. What is presentation of Wegner Granulomatosis?
Usually affect middle-aged males
Sinusitis or nasopharyngeal ulceration
Hemoptysis with bilateral nodular lung infiltrates
Hematuria due to RPGN (HY)
Serum C-ANCA level correlate with disease activity
18. How do you diagnose Wegner Granulomatosis? How do you treat it?
Pt are C-ANCA (cytoplasmic - anti neutrophil cytoplasmic antibodies) positive.
Biopsy shows large necrotizing granuloma with adjacent necrotizing vasculitis.
Treatment is Cyclophosphamide and corticosteroids. Relapse is common.
Fig - large necrotizing granuloma seen in Wegner granulomatosis. Granulomas are absent in microscopic
polyangiitis.
19. What is microscopic polyangiitis (type of small vessel vasculitis)? Contrast this disease with Wegner
granulomatosis (WG).
Necrotizing vasculitis involving multiple organs (hence the name polyangiitis), especially lung and kidney
(similar to WG).
It's very similar to WG but nasopharyngeal involvement and granulomas are absent.
Serum P-ANCA (perinuclear - anti neutrophil cytoplasmic antibodis) correlate with disease activity instead
of C-ANCA.
Treatment is same as WG - corticosteroids and cyclophosphamide. Relapses are common.
20. What are C-ANCA and P-ANCA?
In C-ANCA, anticytoplasmic antibodies mainly target cytoplasm away from nucleus. In P-ANCA,
anticytoplasmic antibodies mainly target cytoplasm in perinuclear area (hence the name - perinuclear).
21. What is Churg-Strauss syndrome ( a type of small vessel vasculitis)?
Necrotizing granulomatous vasculitis with eosinophils.
Involves multiple organs, especially lungs and heart.
Asthma and peripheral eosinophila.
P-ANCA correlate with disease activity.
Microscopic Polyangiitis
No eosinophila or asthma
Hypertension
Malignant
Clinically silent
Arteriosclerosis
Artherosclerosis
2. Describe histology of artherosclerosis.
- Artherosclerosis is an intimal plaque that obstructs blood flow. It contains necrotic lipid core with
a fibromuscular wall. The lipid core can undergo dystropic calcification.
Fig - artherosclerosis. M is the media, I is the intima, the circle represents the necrotic lipid core
with cholesterol crystals. The necrotic core is surrounded by a fibromuscular wall.
3. What are 4 most common sites for artherosclerosis?
- Note artherosclerosis occurs in large and medium sized vessels Abdominal aorta
Vascutis, HTN Page 3.1
Abdominal aorta
Coronary arteries
Popliteal artery
Internal carotid artery
Modifiable
Non-modifiable
HTN
Age
Hypercholesteremia (LDL
increases risk and HDL reduces)
Smoking
Diabetes
5. What is pathogenesis of artherosclerosis?
- Intima is damaged --> lipids gets between intima and media -->lipid is oxidized and then
phagocytozed by macrophage --> this makes fatty streak. Fatty streak is seen as early as
teenagers.
- Inflammation, healing and increased deposition of lipid occurs. A fibromuscular cap occurs due to
inflammation and healing.
6.
a)
from lumen. As artherosclerotic plaque increases, it creates diffusion barrier resulting in atrophy
of media and adventitia.
Arteriolosclerosis
7. What is arteriolosclerosis?
- Narrowing of small arterioles.
- Causes - deposition of hyaline or hyperplastic media.
8. What is hyaline arteriolosclerosis?
- Proteins leaking into vessel wall causes vascular thickening
- Seen as pink hyaline on microscopy
Fig - flea bitten kidney classic of hyperplastic arteriolosclerosis due to pin point hemorrhage leads to ARF. Contrast glomerular scarring in chronic renal failure due to arterionephrosclerosis
Monckeberg medial calcific sclerosis
14. Describe Monckeberg medial sclerosis.
- Calcification of media
- Does not obstruct lumen, therefore not clinically significant
- Seen as incidental finding in X-ray or mammography
Fig- Enclosure shows monckeberg medial sclerosis. Note how it's limited to media and doesn't
have much effect on lumen diameter.
Fig - normal aorta (left); tree bark like aorta in tertiary syphilis (right)
9.
-
10. What is the most common site of abdominal aortic aneurysm (AAA)? Why is this the most
common site?
- Below the renal arteries and above aortic bifurcation
- Vasa vasorum stops at the level of renal artery bifurcation. Therefore, artherosclerosis of aorta
below this level leads to high level of media atrophy due to poor diffusion of nutrient and gases.
The weak aortic wall leads to aneurysm. (note - most common location of artherosclerosis in
human is abdominal aorta).
Fig: normal abdominal aorta (left); AAA (right) - note calcification of vessel wall and thrombosis
11. What is presentation of AAA?
- >60 year old smoker male with HTN
- Pulsatile abdominal mass that grows with time
12. What is complication of AAA?
- Rupture, especially when >5cm in diameter
- Presents with triad of hypotension, pulsatile abdominal mass and flank pain.
Fig - unstable angina in coronary artery. Note the dark thrombus. The thrombus has high chance of
growing and leading to MI.
7.
-
- Hallmark of irreversible damage to cell is membrane leak. So, cardiac enzymes will leak.
- Troponin I - most sensitive and specific marker
Rises 2-4hrs post infraction
Peaks at 24 hrs
Returns to normal 7-10 days
- CK-MB - useful for detecting reinfarction
Rises 4-6 hrs after infraction
Peaks at 24 hrs
Returns to normal by 72 hours
14.
-
Fig - the box shows necrotic myocytes (no nuclei) and the circles show contraction band necrosis
15. Describe time frame of MI (HY)
Time
Complication
<4 hrs
none
none
- Cardiogenic shock
- CHF
- Arrhythmia
Dark discoloration
1-3
weeks
Months Fibrosis
White scar
- Aneurysm
- Mural thrombosis
- Dressler syndrome (autoimmune pericarditis)
(HY)
Arrhythmia doesn't happen post 24 hrs because the conduction system is already damaged and necrosis
occurs < 1 day.
Fibrinous pericarditis only occur with transmural infaract
Papillary muscles are fed by right coronary artery
Dressler syndrome - inflammation of pericardium and exposure of pericardial antigen can cause
autoimmune attack to pericardium
<1 day
1 day - 1 week
1 week- 1 month
>1 month
Coagulative necrosis
Granulation tissue
Scar tissue
Dark discoloration of
heart
Yellow pallor
Fig - fibrinous pericarditis (fibrin exudate during neutrophil rich stage (day 1-3 post MI) rubs when hear
contracts producing and characteristic friction rub). Only see during transmural infraction
Fig - 1-3 weeks post MI. The yellow pallor is central area of necrosis (granulation tissue?) surrounded by
emerging blood vessels from edge of infaract
- HTN
- Dilated cardiomyopathy
- MI
- Restrictive cardiomyopathy
1.
-
2. If there's a left-right shunt in heart, which direction does it initially present? Why does it reverse?
- Early shunt is left to right due to reduced resistance in pulmonary circulation.
- Shunt later becomes right to left - pulmonary circulation increases resulting in pulmonary HTN and
hypertrophy of pulmonary vessels
3. What is Eisenmenger syndrome (aka tardive cyanosis)?
- Serious hypoxemia caused by reversal of left-to-right shunt is called Eisenmenger syndrome.
- It can be present during atrial septal defect, VSD or patent ductous arteriosus
4.
-
VSD
1. What's most common congenital heart defect? What is it associated with (HY)?
- Ventricular septal defect
- It's associated with fetal alcohol syndrome
- Aorta arises from right ventricle and pulmonary artery arises from left ventricle. Right side does
systemic circulation and left side does pulmonary curculation
- Left and right sided blood never mix (early cyanosis)
- Association:
ASD alone or ASD + VSD
Coarctation of aorta
1. What's coarctation of aorta? What are two types?
- Coarctation of aorta is narrowing of aorta
Infantile type
Adult type
Aortic stenosis
1. What are some causes of aortic stenosis?
- Normal wear and tear of valve
- Bicuspid aortic valve (speeds up wear and tear)
- Chronic rheumatic fever
2. What is its presentation?
- Presents in late adulthood (>60 years)
- Crescendo-decrescendo murmur with systolic ejection click (click is when the valve opens?)
3. How do you distinguish stenosis from chronic rheumatic fever vs normal wear and tear?
- In chronic rheumatic fever, there is fusion of commissures of aortic valves. Also, we see mitral
stenosis.
4.
-
8.5 Endocarditis
1. What is endocarditis?
- Inflammation of endocardium (mostly valves) usually due to bacterial infection.
Pathogen
1.
-
S. viridans
S. aureus
S. epidermidis
Strep bovis
Cause endocarditis in pt
with colorectal carcinoma
(HY)
HAECK organism
Hemophilus,
Actinobacillus,
Cardiobacterium,
Eikenella, Kingella
Nonbacterial
thrombotic
endocarditis
Occurs if pt is
hypercoagulable or has
adenocarcinoma
Libman-Sacks
endocarditis
Sterile vegetations on
both side of mitral valve
Coxiella burnetti
Fig - roth nodules (retinal hemorrhage); osler and roth nodules are immunologic.
Endocarditis may lead to glomerulonephritis and positive Rheumatic factor.
6. How does endocarditis lead to low blood iron.
- Acute phase reactant proteins are made (hepsidin being one major one). Hepsidin traps iron in
storage site. This leads to high ferritin. Also, bone marrow takes iron from blood because hepsidin
is trapping iron in storage site. Thats how serum iron decreases.
7. Describe nonbacterial thrombotic endocarditis.
- It is sterile vegetation seen on valves during hypercoagulable state or underlying adenocarcinoma.
Cardiac Page 5.2
8.6 Cardiomyopathy
1.
-
2.
-
Fig - myocarditis; notice the presence of lymphocytes. Most common cause is coxcakie virus;
acutely, it can cause death; in chronic cases, it can cause dialated cardiomyopathy
3. What is treatment for dialated cardiomyopathy?
- Nothing; pt need transplant
Hypertrophic cardiomyopathy
4. Describe hypertrophic cardiomyopathy.
- Massive hypertrophy of left ventricle
- Most common cause (HY): due to autosomal dominant mutations in sarcomere proteins
5.
-
Myxoma
Rhabdomyoma
Metastasis
Benign hamartoma of
cardiac muscle
Fig: rhabdomyoma
Metastasis
1. What is most common type of cardiac tumor?
- Metastasis (more common than primary tumors)
2. What are common sites of metastasis?
- Breast, lung carcinoma, melanoma and lymphoma
3. What is its most common presentation?
- Most commonly affects pericardium and seen as pericardial effusion
Nasopharynx
1. Differentiate angiofibroma and nasopharyngeal carcinoma.
Defn
Angiofibroma
Nasopharyngeal carcinoma
Biopsy
Rhinitis
Nasal polyp
Rhinovirus no 1 cause
Laryngeal carcinoma
Defn
Benign papillary tumor of vocal cord SCC of epithelial lining of vocal cord
Cause
Acute epiglottitis
laryngotracheobronchitis (croup)
xray
Fig: vocal cord nodule (usually bilateral and seen on true vocal cord)
Bronchopneumonia
- Cause is mostly
bacterial
- Cause is mostly
bacterial
- Most common
cause:
Strep.
Pneumoniae
(95%)
Klebsiella
pneumoniae
H influenziae
Bacterial causes:
- Mycoplasm pneumoniae
- Chlamydophilla
- Legionella (pathoma puts legionella in broncho)
Treat: ceftriaxone
Treatment:
Fig - lobar pneumonia (right), bronchopneumonia (middle), interstitial pneumonia (left). Note lack of alveolar
exudate in interstitial pneumonia
Pulmonary Page 2.1
Klebsiella pneumoniae
Broncho pneumonia
bacteria
Association
Staph aureus
Haemophilus
influenzae
Pseduomonas
aeruginosa
Moxarella catarrhalis
Legionella
pneumophila
Atypical pne
organism
Association
Mycoplasma
pneumoniae
Chlamydia
pneumoniae
Respiratory
Most common cause of pneumonia in infants
syncytial virus (RSV)
Cytomegalovirus
(CMV)
Influenza virus
Coxiella burnetti
Pneumonia with high fever (Q fever; generally, pneumonia has low fever)
Associated with farmers and veterinarians
Coxiella is different from rickettsia in 3 ways: causes pneumonia, does not require
arthropod for transmission (transmitted as spores), does not produce rash
Tuberculosis
1. Describe presentation of primary TB.
Caused by inhalation of bacteria.
Presentation:
Focal caseating necrosis classically in lower lobe and hilar lymph nodes
The foci undergo fibrosis and calcification resulting in Ghon complex
Mostly asymptomatic
Leads to positive PPD
Fig: Ghon complex (calcified and fibrosed lung): classic location is subpleural region near hylar nodes
1. Describe presentation of secondary TB (aka reactivated TB).
Commonly seen due to immunosuppression, AIDS, or old age
Presentation:
Usually affects upper lobes
Forms many focal caseating necrosis, or miliary TB or TB bronchopneumonia
Symptoms:
Fevers and night sweats
Cough with hemoptysis
Weight loss
9.
Chronic bronchitis
Fig: Cross section of chronic bronchitis. Top right portion has respiratory epithelium, bottom left
has cartilage. It's clearly visible that mucus glands make >50% thickness of airway.
Emphysema
8. What is emphysema?
Destruction of alveolar air sac and multiple sacs combine to become one.
Due to loss of elasticity of air sacs, lung becomes like a shopping bag, not effectively expelling air
out.
Also, elasticity of air sacs attached to bronchioles keep the bronchiole open during expiration.
When the sacs are gone, then bronchioles collapse during expiration.
Fig: Histology of emphysema showing multiple air sacs combining to make one.
9. What is pathophysiology of emphysema?
Imbalance between protease and antiprotease. Inflammation induces high protease activity. So,
smoking leads to inflammation which leads to emphysema.
10. Differentiate two classic causes of emphysema (destruction of alveolar air sacs).
Smoking (no. 1 cause of emphysema)
PiMZ
PiZZ
- Homozygous mutant
- Significant risk for panacinar emphysema and cirrhosis
15.
-
IL-5
Attracts eosinophils
IL-10
- IgE coats mast cells and next time same allergen is encountered, massive mast cell degranulation
occurs.
- Histamines (arteriolar vasodilation and increase vascular permeability) and leukotriene
(vasoconstriction, increased vascular permeability (by constricting pericytes), and
bronchoconstriction) are released by mast cells.
Pulmonary Page .4
1.
-
Complication
Presentation
Berylliosi Beryllium
s
miners
Aerospace
workers
Asbestos Construction
is
workers
Plumbers
Shipyard
workers
Fig: A: Asbestos body (ferritin and hemosiderin coated asbestos particle); B: pleural plaque on
diaphragmatic pleura; C: Silicotic nodule, notice lots of collagen with minimum inflammation
5. What is presentation of sarcoidosis?
- Sarcoidosis is non-caesating granuloma in multiple organs (most commonly localized in lungs and
hyalar lymph nodes)
- Presentation: non specific - fatigue, wt loss, joint pain and arthritis
- Others: uveitis, erythema nodosum, cardiac sarcoidosis, neurosarcoidosis (affects CN often)etc
- Hypercalcemia (HY) 1 alpha hydroxylase activity of epithelial histiocytes convert vit D to active form
- Asteroid bodies are seen in biopsy (not-specific; can be seen in giant cells of any granulomas)
Hemosiderin
Intracellular protein that acts as buffer against Fe overload or Intracellular complex made of
shortage (protein can be secreted too)
Ferretin and other stuff
Fe in Ferretin can be given out when needed
Pulmonary Page .2
to body
Plasma Ferretin correlates well with total Fe in body; so serum
ferretin a common test to access anemia.
Fig: hyaline membrane seen on alveoli represents ARDS (right); diffuse whiteout seen in Xray in
ARDS (left)
2. What are causes of ARDS?
- Mechanism is activation of neutrophils that induces protease and free radical damage of type I
and II pneumocytes.
- It's occurs secondary to (100's of causes)
Sepsis
Infection
Shock
Trauma
Aspiration
Pancreatitis
DIC
Hypersensitivity reactions
Drugs
3.
-
2.
-
3.
-
S.N
Cancer type
Remarks
Subtype
Squamous cell carcinoma
Adenocarcinoma
Broncheoalveolar carcinoma (Adenocarcinoma in situ)
Large cell carcinoma
(Bronchial) carcinoid tumor
3
Mesothelioma
Metastasis
- related to asbestos
Paraneoplastic
syndrome
Undifferentiat Excellent
ed and poor prognosis
prognosis
- Small cell
carcinoma
(poorly
differentiated
NE cells)
- Squamous cell
carcinoma
(PTHrp)
- Small cell
carcinoma
- (Bronchial)
- Bronchioalveola - Small cell carcinoma (male
carcinoid tumor r carcinoma
smokers)
(well
(adenocarcinom
differentiated
a in situ)
NE cells)
- Bronchoal
veolar
carcinoma
- Small cell
- Large cell
carcinoma
carcinoma
(ADH, ACTH, Ab
for Ca channel)
- Adenocarcinoma (most
- Large cell
common in female smokers carcinoma (Band non-smokers) HCG)
broncheoalveolar carcinoma
not associated with smoking
- Large cell carcinoma
9. Describe the following types of cancer.
Cancer
Histology
Association
Location
Remarks
- Associated with 5A and 1B
- Produces ACTH
- Produces ADH
- Produces Ab for EatonLambert syndrome
Lambert syndrome
(presynaptic Ca channel Ab)
(paraneoplastic syndromes)
- Anti-neuronal antibody
syndrome (limbic encephalitis,
cerebellar degeneration,
opsoclonus, GI dysmotility,
poly radiculopathy)
- Amplification of myc
oncogene
- LOVES TO GO TO BRAIN - give
prophylactic cranial
irraditation
- MOST AGGRESSIVE TYPE OF
LUNG CANCER
- Most common
tumor in
nonsmokers and
female smokers
Peripheral
- Most common
tumor in male
smokers
Central
Figintracellular
bridge
Central or
peripheral
Central or
- MOST COMMON PRIMARY
peripheral
LUNG CANCER IN CHILDREN
(when central, - Low grade malignancy; rarely,
can cause carcinoid
makes polyp
like mass in
syndrome - caused due to
bronchus)
release of vasoactive
substance (mainly serotonin) flushing, diarrhea, restrictive
cardiomyopathy due to
- Not related to
smoking
- Poor prognosis
- Poor response to
chemotherapy; remove
surgically
- Paraneoplastic - may secrete
B-HCG
Carcinoid
tumor
(when central,
makes polyp
like mass in
bronchus)
Peripheral
- Excellent prognosis
- Pneumonia like consolidation
on imaging
Canon-ball
nodules on
imaging
- Highly associated
with asbestos
exposure (lung
cancer more
common in
asbestos
exposure)
- Malignant tumor of
mesothelial cells
(mesothelium is a membrane
of simple squamous cells that
lines body cavities: pleura ,
peritoneum, mediastinum and
pericardium)
- Tumor encases the lung
- Small cell carcinoma is poorly differentiated neuroendocrine tumor; carcinoid tumor is well differentiated
neuroendocrine tumor.
- Neuroendocrine cells have neurosecretory granules; chromogranin stains positive for neurosecretory granule.
Pulmonary Page 7.4
- Neuroendocrine cells have neurosecretory granules; chromogranin stains positive for neurosecretory granule.
9.9 Pleura
Tension pneumothorax
Cause
Due to failure of facial prominence to fuse one superior, two from sides and two from
inferior - in early pregnancy
Apthous
ulcer
Behcet
syndrome
Oral herpes - Dew drops in petal appearing painful - HSV 1 - usually occur in childhood
ulcer
- Virus remains dormant in trigeminal
ganglia; stress and sunlight can activate
virus and cause ulcers again
2. Describe the squamous cell carcinoma of oral cavity.
Description
Risk factor
Common site
- Floor of mouth
Precursor
lesions
- Leukoplakia
White plaque that can't be removed (unlike candida) - represents
dysplasia
- Erythroplakia (red plaque)
Vascularized leukoplakia and highly suggestive of squamous cell
dysplasia
Fig: erythroplakia (right), leukoplakia (middle), hairy leukoplakia (left - not precancerous)
GI Page 1.1
Cause
Labs
Risk
- Increased amylase
(can be from
pancreas too)
Sterility,
especially in
teenagers
Epidemiology
Location
Composition
Pleomorphic
adenoma
Most common
tumor of SG
Mostly in
parotids
Warthin
tumor
2nd most
common tumor
of SG
Mostly in
parotids
Mucinous and
squamous cell
GI Page 2.1
Presentation
- Involves CN 7
10.3 Esophagus
Description
Presentation
- Vomiting,
- polyhydroamnio
s,
- aspiration,
- abdominal
distension
Esophageal
web
- Dysphagia for
poorly chewed
food
Plummer
venson
syndrome
Zenker
diverticulum
- Halitosis (rotting
food in
diverticulum)
- Dysphagia
- Obstruction
Mallory
- Painful
GI Page 3.1
Mallory
Weiss
syndrome
Boerhaave
syndrome
- Painful
hematemesis
Esophageal varices
Definition
Anatomy
Etiologies
Clinical
features
GI Page 3.2
Risk factor
- Hiatal hernia
- EtOH, tobacco
- Obesity, fat rick diet
- Caffeine
Barret's esohagus
Definition
Fig: squamous epithelia on left, columnar epithelia with goblet cells (right) - barret's
esophagus
Esophageal carcinoma
Adenocarcinoma
Risk factor
- Barret esophagus
GI Page 3.3
Vinson synd)
- Esophageal injury (ex - lye
ingestion)
- Very hot tea
Prognosis
Presentation
Lymph node
involvement
Cervical nodes
Middle 1/3rd
Mediastinal or tracheobronchial
nodes
Lower 1/3rd
GI Page 3.4
10.4 Stomach
Sections of stomach
Omphalocele
Epidemology - M>F
- Presents after 2 weeks of birth
Presentation - Visible peristalsis and projectile non-bilious (non-green) vomiting after eating
- Olive like mass on abdomen
Chronic gastritis
- T cell mediated damage to gastric parietal cells (type 4 - H pylori produces urease to create basic environment; and
hypersensitivity)
protease damages mucosal defense - acidic damage to
stomach
Epi.
Cli.
Feat.
- Atrophy of mucosa and intestinal metaplasia (stomach - Intestinal metaplasia - high risk of intestinal type
biopsy looks like intestine) - high risk of stomach
adenocarcinoma of stomach
adenocarcinoma
- Epigastric abdominal pain
- Achlorhydria (low acid) with increased gastrin levels
- Increased risk of ulceration
and antral G cell hyperplasia
- Megaloblastic anemia (pernicious anemia) due to lack
of IF
Lab
Treat.
Comp.
type)
MALToma
Duodenal ulcer
Gastric ulcer
Cause
Present.
Location
Risk
Biopsy
Risk of
carcinoma
- Duodenal ulcers almost never malignant (duodenal carcinoma - May be caused by gastric
extremely rare)
carcinoma (intestinal subtype)
Presentatio - Presents late with weight loss, abdominal pain, anemia and early satiety
n
- Rarely presents as acanthosis nigricans (hyperplasia and darkening of epidermis) and Leser-Trelat sign (lots of
seborrheic keratosis)
GI Page 4.3
Intestinal type
Diffuse type
Diffuse type
More common
Location
Risk
factor
Histology
- Signet ring cells that diffusely infiltrate the gastric mucosa - nucleus pushed to
edge as tumor cell produces lots of mucin - looks like ring
GI Page 4.4
Mets
GI Page 4.5
Association
- Down syndrome
- Outpouching of all three layers of bowel wall (true diverticulum) due to failure of vitelline
duct to involute (partial involution)
Anatomy
- Developing midgut receives nutrients through vitelline duct from yolk sack
- Vitelline duct forms in 4th week and involutes in 7th week
Partial involution of vitelline duct Merkel diverticulum
No involution
Rule of 2
- Seen in 2% of population
- 2 inches long
- 2 feet away from ileocecal valve
- Presents within first 2 year of life
Volvulus
Intussusception
GI Page 5.1
ischemia
Cause
Pres
Cause
Transmural
infraction
Mucosal
infraction
- Hypotension
Lactose intolerance
Defn
Presentation - Lactose osmotically active (abdominal distension and diarrhea after eating milk products)
Cause
Celiac disease
Defn
Genetics
Pathophys - Gliadin pathogenic component in gluten. After absorption, its deamidated by tissue
transglutaminase (tTG). Deamidated gliadin is presented by APC. CD4 T cells mediate tissue
damage.
Presentati - Chlidren present with failure to thrive, abdominal distention diarrhea
on
- Adults present with chronic diarrhea and bloating
- Dermatitis herpetiformis - small, herpes like vesicles on skin due to IgA deposition on
dermal papillae
GI Page 5.2
dermal papillae
- IgA deficiency may be seen
- All symptoms resolve with gluten free diet
Lab
findings
Biopsy
Fig - Flattened villi with crypt hyperplasia in Celiac (left) and normal villi (right)
Complicati - Small bowel carcinoma and T cell lymphoma despite good dietary control
on
Tropical sprue
Defn
Difference from - Damage most prominent in jejunum and ileum (Vit B12 and folate deficiency - I fuck
celiac
bitches in France) - In Celiac, damage is mostly in duodenum
- Arises after infectious diarrhea and responds to antibiotics
- Occurs in tropical regions - ex-Caribbean
Whipple disease
Defn
GI Page 5.3
Fig - PAS stain in whipple disease (mucin in goblet cells and bacteria inside macrophages
are staining pink)
Abetalipoproteinemia
Defn
Clinical
features
Carcinoid
syndrome (HY)
Presentati - Bronchospasm
on
- Facial flushing
- Diarrhea
- Carcinoid heart disease - right sided endocardial fibrosis, especially in
tricuspid valve and pulmonary valve (not seen in left heart due to
presence of MAO in lungs)
GI Page 5.4
Cause
Presen
- Periumbilical pain, fever, nausea - pain eventually localizes to right lower quadrant
(McBurney point)
- Rupture results in peritonitis that presents with guarding and rebound tenderness
GI Page 5.5
Ulcerative colitis
Chorn disease
Wall
- Mucosal and submucosal layers - Full thickness with knife like fissures
involve
ment
Locatio - Begins at rectum and
n
continuously moves back
anywhere up to cecum
Inflam - Crypt abscess with neutrophils - Lymphoid aggregated with noncaseating granuloma in 50% of
mation
cases
Gross - Psudopolyps
- Cobblestone mucosa
appear - Los of haustra lead to lead pipe - Creeping fat
ance
sign on imaging
- Strictures
GI Page 6.1
GI Page 6.2
10.8 Colon
Hirschprung disease
Definition
Cause
GI Page 7.1
Angiodysplasia
Acquired malformation of mucosal and Autosomal dominant disorder resulting thin walled
submucosal capillary beds
blood vessels, especially in mouth and GI tract
Mostly seen in cecum and right colon
due to high wall tension
Rupture of capillary beds present as
hematochezia in old adults
Cause
Cause
GI Page 7.2
Colonic polyps
1. Differentiate hyperplastic and adenomatous polyps.
Hyperplastic polyp
Adenomatous polyp
Occur due to hyperplasia of glands (polyclonal) serrated appearance on microscopy - both are
identical
Presentation
Gene function
APC (adenomatous
polyposis coli gene) sporadic or germline
increases risk of
polyp formation
K-ras
leads to formation
of polyp
GI Page 8.1
- Autosomal dominant
- APC mutation (chromosome 5)
Turcot
syndrome
FAP + CNS tumor (medulloblastoma and glial tumor) - you put turban on head
Juvenile polyp
Juvenile polyposis
GI Page 8.2
Peutz-Jeghers syndrome
(aka heriditary intestinal
Sporadic or AD (mutation in
SMAD - dont need to know)
Inherited - autosomal
dominant
- Multiple hamartomatous
polyp in GI tract
- Hyperpigmentation (freckle
like spots) on lips, oral
mucosa and genial skin
Colorectal cancer
1. What is colorectal cancer and what's its epidemiology?
- 3rd most common cause of cancer related death
- Peak incidence in 60-70 year olds (both men and women)
2. What are the two molecular pathways that cause CRC?
- Adenoma-carcinoma sequence (most common)
3. Describe microsatellite instability's role in CRC. What disorder is associated with microsatellite
instability?
- Microsatellites are repeating sequences of noncoding DNA; their number is maintained during
cell division (i.e. they're stable)
- Instability indicates defect in DNA mismatch repair enzymes
- Disorder associated:
Heriditary non-polyposis colorectal carcinoma (HNPCC) - aka Lynch syndrome
CRC is de novo (not from adenomatous polyps) at early age and usually right sided.
Adenoma-carcinoma sequence
HNPCC
Seen early
GI Page 8.3
Seen early
Cancer is usually right sided
- Right sided - usually see raised lesion; presents as iron deficiency anemia due to
bleeding and vague pain. Older adult with Fe deficiency anemia has colorectal
cancer until proven otherwise
- Left sided napkin ring lesion:
decreased stool caliber,
left lower quadrant pain,
blood streaked stool
Staging
Serum
marker
- CEA - used to assess assessing treatment response and detecting recurrence; not
useful for screening
GI Page 8.4
Pompe (pump)
Cori (coral)
- Type 2
- Type 3
- Type 5
- Glucose-6-phosphatase
deficiency (last enzyme in
glycogenolysis)
- Lysosomal alpha 1, 4,
glucosidase aka acid maltase
deficiency
- Alpha 1, 6, glucosidase
deficiency (glycogen
debranching enzyme)
- Muscle glycogen
phosphorylase deficiency
- Presentation:
High glycogen in liver
Enlarged kidney
- Presentation:
Cardiomegaly
- Presentation:
Stunted growth
- Presentation:
Severe muscle cramp
during exercise
Myoglobinuria
Increased glycogen in
muscle
Hepatomegaly
- Hepatomegaly
Hepatomegaly
- Severe hypoglycemia
- Hypoglycemia
- Lactic acidosis
- Hypotonia
- Deficiency in lysosomal alpha 1,4 glucosidase (lysol bottle with wand (1), fork (4), glue and daisy bottle) aka acid
maltase (maltese with lemon)
Presentatio - Normal blood glucose - lysosomal breakdown pathway not major source to maintain blood glucose
n
- Hepatomegaly
- Cardiomegaly
- Hypotonia - hippo with tonic
3. Cori's disease (coral)
- Deficiency in glycogen debranching enzyme alpha 1, 6 glucosidase (saw cutting branch, and afro, wand, saxaphone,
glue with daisy)
Presentatio - Normal blood lactic acid level (body can go gluconeogenesis and some glucose can be taken off glycogn) - lake acid
- n
with no up arrow
- Hepatomegaly - glycogen accumulates in liver due to lack of debranching enzyme
- Stunted growth - because body can't mobilize energy source - C clamp
- Hypoglycemia - due to lack of debranching enzyme (hippo-glue bottle)
4. Mcardles disease
- Deficiency in muscle glycogen phosphorylase. Enzyme essential for first step in glycogen breakdown. (muscle glider
with phosphate p)
Presentatio - Increased glycogen in muscle (up arrow in glycogen muscle) - glycogen is trapped in muscle
n
- Painful muscle cramps with exercise (clamps on muscle man) - due to insufficient glucose to muscle
- Myoglobinuria (mayo globe urinal) - dark, brown urine - without enough glucose, muscle breaks down and releases
myoglobin
- Normal lactic acid (lime with bell curve) - Disease localized only to skeletal muscle and body's overall metabolism
isn't severely affected
GI Page 9.3
Hurlers syndrome
- X-linked recessive
- Iduronate sulfatase deficiency
- Alpha-L-iduronidase deficiency
Presentation:
No corneal clouding
Aggressive behavior
Presentation:
Corneal clouding
Developmental delay
Gargoylism
Airway obstruction
Hepatosplenomegaly (due to
accumulation of molecules)
a. Hunters syndrome
Genetics
MOA
GI Page 10.1
b. Hurlers syndrome
- Mucopolysaccharidoses disease - a set of disease where body can't break down long
sugar and they accumulate in various tissue and cause disease
MOA
Presentati - Gargoylism - flat face, depressed nasal bridge, bulging forehead - gargoyl
on
- Airway obstruction - due to craniofacial abnormalities and glycosaminoglycan
deposition in neck tissue
- Corneal clouding
- Developmental delay
- Hepatosplenomegaly
c. Tay Sachs disease (tie with saxophone)
GI Page 10.2
Genetics
- Mutation in hexosaminidase A (hexagon tires with mini A) which breaks down GM2
ganglioside (GM2 car)
- Seen more in Ashkenazi jewish population - jew gangster
MOA
MOA
GI Page 10.3
MOA
GI Page 10.4
Presentatio - Gaucher cells - macrophage with glucocerebroside that look like crumpled tissue
n
paper - crumpled paper
- Hepatosplenomegaly due to glucocerebroside accumulation.
Anemia due to RBC destruction in spleen
Leukopenia and thrombocytopenia
- Bone crisis (crying bone) - severe pain in joints and bone due to glucocerebroside
accumulation
- Erlenmeyer flask deformity - aseptic necrosis of femur that makes it look like
Erlenmeyer flask (necrosis crow with femur)
Fig: Gaucher cell (left), Erlenmeyer flask deformity (middle), normal femur (right)
GI Page 10.5
MOA
Presentati - Globoid cells on histology - enlarged macrophage with multiple nuclei - globe
on
- Developmental delay - due to myelin damage- DD bus
- Peripheral neuropathy - damaged nerves
- Optic atrophy - damage to optic nerve fibers - optic atrophy glasses
GI Page 10.6
Inheritance X linked
MOA
MOA
Presentatio - Globoid cells on histology - enlarged macrophage with multiple nuclei - globe
n
- Developmental delay - due to myelin damage- DD bus
- Peripheral neuropathy - damaged nerves
- Optic atrophy - damage to optic nerve fibers - optic atrophy glasses
GI Page 10.8
Fig - liquifactive necrosis of pancreas with fat necrosis of surrounding fat in pancreatitis
2.
-
- Pancreatic pseudocyst Pt has abdominal mass with persistent increased in amylase after acute pancreatitis.
Pseudocyst rupture cause release of enzyme and digestion and hemorrhage of gut.
- Pancreatic abscess
Usually due to E.Coli. Pt presents with persistently increased amylase.
- DIC - enzymes get on blood, digest coagulation factors
- ARDS - enzymes get to blood, go to lungs and damage alveoli-capillary interface
Chronic pancreatitis
4. What causes chronic pancreatitis?
- Chronic pancreatitis is fibrosis of pancreatic parenchyma which occurs after multiple bouts of
acute pancreatitis
- Etiology
EtOH (most common in adults)
Cystic fibrosis (most common in kids)
Idiopathic
- These etiologies cause repeated attack to pancreas. Other etiology of acute pancreatitis (ex hypercalcemia, scorpion bite etc happen only once or so.
5. What are features of chronic pancreatitis?
- Epigastric pain radiating to back
- Pancreatic insufficiency (small fibrosed pancreas)
Leads to malabsorption with steatorrhea
Fat soluble vitamin deficiency
- Dystrophic calcification of pancreas
- 20 DM in late phase - due to damage of islet cells
- High risk of pancreatic carcinoma
6. Why are serum lipase and amylase not good marker for chronic pancreatitis?
- Because in chronic pancreatitis, pancreas don't produce much enzyme so enzymes aren't
elevated in blood.
Pancreatic adenocarcinoma
7. Describe pancreatic adenocarcinoma, it's risk factor and patient population.
- It's adenocarcinoma arising from pancreatic ducts
- Most commonly seen in elderly
- Major risk factor (HY) Smoking and chronic pancreatitis
8. What is presentation of pancreatic adenocarcinoma?
- If tumor in head of pancreas - obstructive jaundice with pale stool, palpable gallbladder (blocking
of common bile duct)
- If tumor in body or tail or pancreas - 20 DM
- Acute pancreatitis - due to obstruction of duct
- Migratory thrombophelebitis Swelling, erythema and tenderness of extremities
- Serum tumor marker is CA 19-9
If you see thin old pt with sudden onset diabetis, suspect pancreatic adenocarcinoma. Because DM is
usually disease of fat people with onset during middle age, and pancreatic adenocarcinoma is disease of
old people.
9. What is prognosis and treatment of pancreatic adenocarcinoma?
- Very poor prognosis (1 year survival <10%)
Liver and pancreas Page 1.2
3.
-
Cholesterol
stones
Pigment stones
- Black
stones
- Brown
stones
- Risk factors
Extravascular hemolysis (increased bilirubin)
Biliary tract infection (bacteria deconjugates conjugated bilirubin)
6. What are some complications of gallstones? (each are described with questions
below)
- Biliary colic
Pt has waxing and waning RUQ pain (pain starts when gall bladder
contracts against stone; pain goes away when bladder stops contraction)
- Acute pancreatitis and obstructive jaundice
Due to blockage of biliary tree
- Acute and chronic cholecystitis
- Ascending cholangitis
- Gallstone ileus - stone obstructing the intestine lumen
- Gallbladder cancer
Complications of gallstones
7. Describe acute cholecystisis and its presentation?
- Acute cholecystis occurs due to pressure build up in gall bladder due to biliary
tree blockage by stone. Pressure causes squeezing of vessels in gall bladder
wall --> ischemia and bacterial growth
- Presentation
RUQ pain that radiates to scapula (HY)
Fever with elevated WBC count
Increased serum alkaline phosphatase (cell lining biliary tree and gall
bladder contain alk phosphatase)
Risk of rupture if untreated
8. Describe chronic cholecystisis.
- Chronic inflammation of gall bladder due to chemical irritation from long
standing cholelithiasis.
- Hallmark - formation of Rokitansky-Aschoff sinus. (HY)
Note: conjugated bilirubin and direct bilirubin are same thing; non -conjugated and indirect are same.
Disease
Lab values
Etiology
Clinical features
Extravascular hemolysis
(aka ineffective
hemolysis)
High UCB
Physiologic jaundice of
newborn
High UCB
Gilbert syndrome
High UCB
Gilbert syndrome
High UCB
Crigler-Najjar syndrome
High UCB
Absent UGT
Dubin-Johnson
syndrome
High CB
Rotor syndrome
High CB
High CB
High alk
phosphatas
e
Low urine
urobilin
Viral hepatitis
Notes
- Unconjugated bilirubin can't be excreted by urine as it's fat soluble. It floats in blood until it finds exit.
- Conjugated bilirubin is water soluble, can leak out to blood and will go to urine and make it dark
Indication
Choleangitis
Pruritus
Cholestasis
5.
6.
Viral hepatitis
1. What are some causes of viral hepatitis?
- Hepatitis virus A-E (most hep C leads to chronic hepatitis; Hep A,E mainly acute only)
Acute hepatitis can progress to chronic cases
Other causes include CMV and EBV
2. Describe presentation of viral hepatitis.
- Presentation Jaundice (mixed CB and UCB) with dark urine (due to CB)
Fever, malaise and nausea
Elevated liver enzyme (ALT>AST)
Symptoms last < 6 months (if >6 months, it's called chronic hepatitis)
3. Describe histology and pathophysiology of acute viral hepatitis.
- Histology Viral damage occurs both in between hepatocytes and in portal tracts.
- Pathophysiology For Hep virus, it's not the virus that causes the damage; it's the CD8 cells that kill
hepatocytes.
4. What is a common complication and histology of chronic hepatitis?
- Complication - Cirrhosis
- Histology - Inflammation predominantly involves portal tract; not much damage to liver
parenchyma.
Fig - L is liver parenchyma, P is portal tract. Note inflammation is mainly in portal tract only.
5. Describe Hep virus A and E.
Transmission
Hep A
Hep E
- Feco-oral
- Common in
travelers
- Feco-oral
- Commonly acquired from uncooked seafood or contaminated
water
- See Hep E
marker
Describe Hep D.
It can't infect by itself and depends on HBV for infection.
Coinfection - if HBV and HDV infect at same time
Superinfection - if HBV infects pt with preexisting HDV (more severe than coinfection)
Fig - note the regenerative nodules with fibrosis in between - characterstic of cirrhosis.
(normal liver surface is smooth)
2. What mediates fibrosis?
- Stellate cells (that lie below endothelial cells) secrete TGF-beta which mediates the fibrosis.
3.
-
Wilson's disease
Mutation in gene that regulates enterocyte Mutation in ability to excrete Cu into bile and ability to
Fe metabolism
load Cu in ceruloplasmin
9. Describe hemochromatosis.
- Excess iron deposition (hemosiderosis) leads to tissue damage (hemochromatosis)
- Damage due to generation of free radical by Fenten reaction (HY).
10. Describe the MOA of primary hemochromatosis.
- Almost all Fe from diet is absorbed and stored by enterocytes. They regulate how much Iron to
supply to body.
- There's no real way to get rid of Iron (bile and bleeding excretes little bit)
- In hemochromatotis, the regulatory mechanism of enterocytes is lost and all Fe is absorbed.
- Mutation in HFE gene (most commonly c282y) leading to disregulation of enterocytes leads to 1 0
hemochromatosis.
11. What are some secondary causes of hemochromatosis?
- Receiving blood transfusion
12.
-
Hepatic cancer
19. Describe hepatic adenoma.
- Benign tumor of hepatocytes
- Associated with oral contraceptive use; tumor goes down with cessation of drug (HY)
- Risk of rupture because tumor is right below liver capsule - lead to hemorrhage, especially during
pregnancy
20. What are risk factors for hepatocellular carcinoma?
- Chronic hepatitis (usually caused by hep B and C)
- Anything that leads to cirrhosis - hemochromatosis, wilson's, NAFLD, EtOH FLD, alpha-1 antitrypsin
deficiency
- Aflatoxins derived from Aspergillus (HY) - countries that store grains can have Aspergillus grow on
them and they have high incidence of hepatocellular carcinoma
Aflatoxin causes mutation in P53 mutation
21. What's relationship between hepatocellular carcinoma and Budd-chiari syndrome?
- Hepatocellular carcinoma loves to invade hepatic vein and cause Budd-chiari
- Presents with painful hepatomegaly and ascites (SAAG <1.1 g/dl)
22. What is prognosis of hepatocellular carcinoma?
- Poor; tumor are detected late as symptoms are masked by cirrhosis
23. What's a serum marker for hepatocellular carcinoma?
- Alpha-fetoprotein
24.
-
Fig - multinodular liver is classic presentation of liver metastasis and can be felt on physical exam
12.1 Congenital
Dysplastic kidney
1. What is presentation of dysplastic kidney? Is it inherited?
- Mostly unilateral and non-inherited malformation of renal parenchyma with cysts and abnormal
tissue (ex-cartilage).
- Congenital but non-inherited
- If bilateral, must be distinguished from polycystic kidney disease
Fig: dysplastic kidney. Circle on left is cyst; circle on right shows growing cartilage
Polycystic kidney disease (PKD)
1. What is presentation of polycystic kidney disease?
Renal Page 1.1
- Presents in infants as worsening renal - Presents in young adults with HTN (due to increased
failure and hypertension
renin), hematuria and worsening renal failure
- Newborns may have potter sequence
- Associated with (HY):
congenital hepatic fibrosis (see
signs of portal HTN) and
hepatic cysts
- Associated with:
berry aneurysm in brain - family history of renal
disease and brain related death
hepatic cysts, and
mitral valve prolapse
- Think as cyst in kidney, liver and brain.
- Mutation in APKD1 (adult polycystic kidney disease 1)
or APKD2; cysts develop over time
a) Classify the types of acute renal failure (azotemia) and its presentation.
- Pre-renal azotemia
- Intra-renal azotemia
Acute tubular necrosis (most common cause of ARF)
Acute interstitial nephritis
- Post-renal azotemia
- Presentation
Azotemia - hallmark (increase BUN in blood; uremia is symptoms due to increased BUN)
Oliguria (if we make <500ml urine/day, we can't excrete solid waste)
b)
-
Fig- ATN - T are tubules that are clogged up by dead cells. G is glomerulus.
c)
-
Fig - effacement of foot process. Bottom part is capillary; black blobs are RBC.
3. Describe presentation of FSGS.
Most common cause of nephrotic syndome in hispanics and blacks.
Risk factors - most common in people with AIDS, heroin and sickle cell disease (HY). However,
most disease are idiopathic.
Diagnosis - No serology, do biopsy. See focally segmental glomerulus.
Treatment - not great but treat with steroids, immunosuppresants, control BP
4. Describe biopsy finding in FSGS
Glomerulus is sclerosed (hardened) by hyalinosis (proteins and lipid deposition) in focal (only
some glomerulus affected - <50%) and segmental (only a part of glomerulus is affected) pattern.
Fig - notice the small spikes and holes on PAS or silver stain. Holes are immune deposits as
they don't bind to silver. Spikes are new basement membrane laid on top of holes. They bind
to silver and stain dark.
Small and frequent deposits seen in EM. Immune deposition is subepithelial (below
epithelium - podocytes also called epithelium)
Pathology
Description
Post Strep GN
IgA
Alport syndrome
Goodpasture
Fig - cellular crescent seen in RPGN. Note crescent made of fibrin and macrophage (inflammatory
stuff - not collagen)
8. What are etiologies of RPGN?
Etiologies can be distinguished based on immunofluorescence pattern
IF Pattern
Disease
Linear (anti-basement
membrane Ab)
Goodpasture syndrome
Negative IF (pauci-immune)
Comment
s
eosinophila, asthma)
9. Describe Goodpasture syndrome
Antibodies are made against collagen in glomerulur and alveolar basement membrane
Pt presents with hematuria and hemoptysis
Classically seen in young adult males
10. Describe diffuse proliferative glomerulonephritis (nephritic syndrome).
Diffuse Ag-Ab deposition in sub-endothelial location
Most common type of renal disease in SLE (lupus) (VHY) - most common cause of death in lupus
patients is renal failure
11. How do you distinguish Wegner granulomatosis vs Goodpasture syndrome?
Both of them may have hemoptysis and hematuria with RPGN. However, if you see sinus
problems, then suspect Wegner. Because in Wegner's, nasopharynx is affected.
Distinguish by IF as well
13. Describe IgA nephropathy (nephritic)
Most common nephropathy worldwide
IgA deposition seen in mesangium - gives granular IF
Seen due to vesiculoureteral reflux (in chidren) or obstruction - malformation of ureter entering
bladder increases can increase chances of vesiculouretal refux
9. What are clinical features of chronic pyelonephritis?
See cortical scarring with blunted calyces
Scarring of upper and lower pole is characterstic of vesiculoureteral reflux
Histology
See "thyoidization of kidney" - atrophic tubules have proteinaceous mateiral resembling
thyroid follicles.
Waxy casts may be present in urine
12.6 Nephrolithiasis
Causes
Calcium
oxalate
and/
Calcium
Phosphate
Most common
type
(usually see in
adults)
Treatment
Comments
Staghorn
stone - nidus
for infection
Aka struvite
stone
Uric acid
Third most
common (5%)
Radiolucent
(others are
radiopaque)
Cysteine
Rare; most
commonly
seen in
children
Hydration and
alkalinization of urine
May form
staghorn
stone
Notes:
In Chron's, damage to small intestine causes increased absorption of oxalate. This results in high
chance of forming calcium oxalate in urine
Fig - staghorn AMP stone. If you see staghorn stone in adult, think uric acid stone; if you see
in kid, think cysteine stone.
Questions
Is acute kidney injury, acute renal failure and uremia the same thing?
Angiomyolipoma
1. What's angiomyolipoma? What's its associated with?
- Hamartoma made up of blood vessels, smooth muscle and adipose tissue (clear from name)
- It's associated with tuberous sclerosis (HY) (syndrome with benign tumor primarily in brain, eyes,
heart, kidney, skin and lungs. Common presentation: seizures, developmental delay, intellectual
disability and autism)
Wilm's tumor (nephroblastoma) (most common malignant renal tumor in children; average age 3
years)
1. What's histologic hallmark of Wilm's tumor?
- Blastema (primitive kidney mesenchyme cells that make glomerulus, tubules and stromal cells)
Denys-Drash
syndrome
Beckwith-Wiedemann syndrome
W = Wilm's tumor
- Wilm's tumor
A = Aniridia (lack of iris)
- Progressive
G = genital abnormalities
glomerular disase
R = Retardation (developmental - Male
and motor)
pseudohermaphro
ditism
- Wilm's tumor
- Neonatal hypoglycemia
- Muscular hemihypertrophy (big muscles
on one side of body)
- Organomegaly (specially tongue)
- Mutation of WT1
gene
Heriditary tumor
Fig: gross feature (left) and microscopic feature (right) of renal cell carcinoma
Risk factor
Common
location
Bladder.
Adenocarcinoma
Bladder
Fig: extrophy
- Urachal remnant - urachus is remnant of channel between bladder and umbilicus (urine drains this way in
fetus during 1st trimester of pregnancy). It's lined by glandular cells. From 12th week of gestation, it's called
median umbilical ligament.
2. What are clinical characters of urothelial carcinoma?
- Generally seen in older adults as painless hematuria
- Tumor are multifocal and recur (entire urothelium is mutated via mechanism called field defect - ex- cigarette
smoking hits entire urothelial lining)
3. What are two pathways of urothelial carcinoma (HY)?
Flat
Papillary
LP is lamina propria
13.1 Vulva
1. Describe the following conditions about vulva.
Anatomy
Skin and mucosa outside hymen (labias, mons pubis and vestibules)
Histology
Bartholyn cyst
Condyloma
Lichen sclerosis vs
lichen simplex
chronicus
Lichen sclerosis
Vulvar carcinoma
Epidemiology
Epidemiology
Cause
Presentation
Pathophys of
HPV cases
- Presence of malignant epithelial cells in epidermis of vulva (carcinoma in situ) usually no underlying malignancy (contrast to Paget disease of nipple where
there's underlying carcinoma)
Presentation
Fig: paget disease of nipple vs vulva (can occur in scrotum and other places
too)
Distinguish
Paget cells - PAS+ve, keratin +ve and S100 -ve
from melanoma Melanoma - PAS-ve, keratin -ve and S100 -ve (PAS - shows mucus)
13.2 Vagina
1. What type of cell lines the vagina?
- Non-keratinizng squamous epithelial cell
2. Describe vaginal adenosis.
Definition
Cause
Pathophys
Cause
13.3 Cervix
1. What are differences between exocervix and endocervix?
Exocervix
Endocervix
Progression
- Can progress to carcinoma in situ and invasive squamous cell carcinoma of cervix
- Progression not inevitable
Grades of
dysplasia
HPV
Prognosis - Mostly affects lower genital tract, especially cervix in transformation zone
- Infection usually eradicated by acute inflammation; persistent infection can lead to cervical
dysplasia and cervical intraepithelial neoplasia (CIN)
- Most common cause of SCC of genitourinal tract
Pathophys - Produces proteins:
E6 - inactivates p53
E7 - inactivates Rb
Vaccinatio - HPV 6, 11
n
Prevent against condolymata acuminata
- HPV 16, 18
Prevent against CIN and cervical cancer
Cervical carcinoma
Types
- Cervical cancer went from being the most common to one of least common gynecologic cancers in US
Goal
Frequency
Process
Confirmatory
test
Limitations
- Pap smear great for squamous cell carcinoma but not for adenocarcinoma of cervix
- If transformation zone not sampled, then false negative results may be seen
Normal
histology and
pap smear
Fig: right - normal squamous epithelial cells (small nuclei with abundant cytoplasm) present
in exocervix; left normal squamous epithelial cells (red arrows), normal columnar
epithelial cells from endocervix blue cytoplasm and cilia sometimes seen
Abnormal pap
Abnormal pap
smear
Fig: black arrows indicate normal squamous epithelial cells with small round nuclei. Red
arrow - koliocytes - abnormally large and pleomorphic nuclei
Myometrium
Hormone cycle of
endometrium
Proliferative
phase
Estrogen driven
Endometrium grows
Menstrual
phase
Endometrium falls
Due to loss of
progesterone
Anovulatory
cycle
- Lack of ovulation
- Due to lack of ovulation, corpus luteum doesn't develop and progesterone isn't
made. Endometrium develops by estrogen but fails to be maintained; so it falls
off
- Common cause of dysfunctional uterine bleeding during menarche and
menopause
Chronic endometritis
Cause:
- Usually due to retained product of
conception (after delivery or
miscarriage) - serves as nidus of
infection
Causes:
- retained products of conception,
- IUD,
- TB, or
- pelvic inflammatory disease (gonorrhea,
chlamydia)
Endometrial polyp
Definition
Endometriosis
Definition
- Endometrial glands and stroma outside uterine endometrial lining (the glands
follow normal menstruation cycle)
Cause
Common
sites
Cause
- Unopposed estrogen
Obesity
Polycystic ovary syndrome
Estrogen replacement
Sporadic pathway
- Risk factors are increased estrogen - Carcinoma arises sporadically in atrophic endometrium
exposure:
without any evident precursor lesion
Early menarche/late
- P53 mutation common; tumor is agressive
menopause
Nulliparity (no babies)
Infertility with anovulatory
cycle
Obesity
- Average age of presentation 60
years
Cause
13.5 Ovary
Location
+ve
stimulus
Response
Granulosa
cells
FSH
Theca cells
Surround Granulosa
cells
LH
Produce androgens
- Estradiol surge causes LH surge which leads to ovulation (beginning of secretory phase of
endometrial cycle)
- After ovulation, follicle becomes corpus luteum which primarily secretes progesterone (drives
the secretory phase and prepared endometrium for possible conception)
2. Define hemorrhagic corpus luteal cyst and follicular cysts.
Cyst type
Presentation/cause
Hemorrhagic corpus - Caused by hemorrhage into corpus luteal cyst. (Corpus luteal cysts are
luteal cyst
formed if corpus leutem fails to disintegrate and instead persists)
- Normal; commonly found during early phase of pregnancy
Follicular cyst
Epidemiology/remarks
Surface
epithelium
Germ cells
Oocytes
Placental - Choriocarcinoma
tissue
Sex cord
stroma
Fetal
tissue
- Embryonal carcinoma
- Cystic teratoma (most common
germ cell tumor)
Yolk sac
- Granulosa-theca
tumor
- Sertoli-Leydig cell
tumor
- Fibroma
Fibroblasts
Borderline
- In between feature between benign - Has complex cyst with thick, shaggy lining
ad malignant
- Better prognosis than malignant but
has malignant potential
(30-40 years)
(60-70 yrs)
Endometroid tumor
Brennor tumor
Mostly malignant
Mostly benign
4. Describe the following features of surface epithelial tumors of female reproductive tract.
Distant metastasis Peritoneum (via direct contact) - see omental caking
Serum marker
Choriocarcinoma
Embryonal
carcinoma
Malignant tumor
composed of
cytotrophoblasts and
syncytiotrophoblasts
Malignant
Malignant (trophoblasts
are very invasive
Malignant
(aggressive)
Malignant
Fig: Schiller-Duval
bodies (glomerulus like
structure) classically
seen on biopsy.
Cystic teratoma
- High Beta-HCG
characterstic (made by
syncytiotrophoblasts) may lead to thecal cysts
in ovary
- Hyperthyroidism in case of
Struma ovarii (teratoma
mainly composed of
thyroid tissue)
Fibroma
Benign tumor
Cells may produce androgens:
- Associated with pleural effusions and
- See hirsuitism and virilization (more ascites (meigs syndrome) - syndrome
masculine)
resovles with removal of tumor
Presentation
Krukenberg tumor
- Mucinous tumor
- Mostly bilateral (if unilateral, think primary mucinous
carcinoma of ovary)
Mucinous tumor of
appendix
Mucinous tumor of
appendix
Risk
Presentation - Lower quadrant abdominal pain a few weeks after a missed period
Prognosis
Spontaneous abortion
Definition
Teratogens
1. What is common timewise effect of teratogen exposure?
0-2 weeks of gestation Spontaneous abortion
3-8 weeks
3-9 months
Teratogen
Effects
Alcohol
Cocaine
Thalidomide
- Limb defects
- Spontaneous abortion
- Hearing and visual impairment
Tetracycline
- Discolored teeth
Warfarin
- Fetal bleeding
Phenytoin
Placental abruption
Placenta accreta
Placenta implants
and closes cervical
- Presents as
- Presents as painful 3rd trimester
painless 3rd
bleeding and fetal insufficiency
trimester bleeding
- Often requires Csection delivery
Eclampsia
HELLP
- Warrant
immediate
delivery
- Sleeping on stomach
- Exposure to cigarette smoke
- Prematurity
Presentation
Classification
Treatment
- Suction curettage
- Monitor B-HCG subsequently to ensure entire mole is removed
completely
Complication
Complete mole
Genetics
Fetal tissue
Present
Absent
Risk for
choriocarcino
ma
2-3%
Minimal
14.1 Penis
Presentation
Cause
Priaprism
Hypospadis
- Due to failure of
urethral folds to close
Epispadias
- Due to abnormal
positioning of genital
tubercle
- Associated with bladder
exstrophy (bladder
located outside body
cavity)
Phimosis
- HPV 6, 11
Characterized by
Condyloma
acuminatum
- Characterized by
koliocytic changes
- Chlamydia trachomatis
(serotype L1-L3)
Precursor
lesions:
14.2 Testicle
Notes
Yes
Mumps
Autoimmune orchitis
- Characterized by granulomas
involving seminiferous tubules
Yes
Testicular torsion
Definition
Cause
Presentatio Sudden testicular pain and absent cremasteric reflex (nerves present in cord)
Male GU Page 2.1
Presentatio Sudden testicular pain and absent cremasteric reflex (nerves present in cord)
n
Hydrocele
Spermatoce
le
Cause
- Incomplete closure of
processus vaginalis and
its communication with
peritoneal cavity - in kids
- Blockage of lymphatic
drainage - adults
- Do radical orchiectomy (mass not biopsied due to risk of seeding the scrotum)
Sex cord
stroma
(mostly
benign)
Seminoma
Non-seminoma
Most common
testicular tumor
55% of germ cell
tumors
Highly responsive to
radiotherapy
Metastasize late
Metastasize early
Excellent prognosis
Poor prognosis
Include teratoma, embryonal carcinoma, endodermal sinus tumor,
choriocarcinoma and mixed germ cell tumor
Teratoma
Embryonal
carcinoma
Most common
testicular tumor
Malignant
Endodermal sinus
(yolk sac)
Choriocarcinoma
Most common
testicular tumor in
children
Malignant (in
Malignant
females, it's mostly
benign)
Malignant
Malignant; spreads
early
- Immature cells
that may
produce glands
- Forms
hemorrhagic
mass with
necrosis
- Schiller-Duval
- Tumor of
bodies on histology cyncytiotrophoblasts
(glomerulus like)
and cytotrophoblasts
(placenta like tissue
but absent vilil)
- B-HCG rarely
increased
- AFP or B-HCG
incresed
- AFP increased
- AFP or B-HCG
increased
- B-HCG increased
(syncytiotrophoblasts
produce it)
- Alpha subunit of HCG
similar to FSH, LH and
TSH; may see
hyperthyroidism and
gynecomastia
14.4 Prostate
Chronic prostatitis
- Causes:
Chlamydia and gonorrhoeae in young adult
E coli and pseudomonas in old adults
- Presentation:
Dysuria with fever and chills
On DRE, prostate is tender and boggy
- Presentation:
Dysuria with pelvic or lower back
pain
- Prostatic secretion:
WBC high
+ve bacterial culture
- Prostatic secretion:
WBC high
-ve bacterial culture
Clinical
features
Labs
- Slightly increased prostate specific antigen (PSA) - made by prostatic glands and it
liquefies semen (still <10 ng/ml)
Treatment
Prostate adenocarcinoma
Diagnosis
Biopsy:
See small invasive glands with prominent nucleoli
Ducts maybe only one layer thick instead of having basal and laminal layer
Metastasis
Treatment
Hormones by hypothalamus
4. Growth hormone
5. Somatostatin
3.
-
Fig - rough sketch of terminal duct (TD) and lobular unit (LU)
Hypopituitary
8. When do we see hypopituitarism?
- When >75% of pituitary parenchyma is lost
9. What are some causes of hypopituitarism?
- Pituitary adenoma (common cause in adults ) - mass effect or apoplexy (bleeding in adenoma)
reduces hormone production
- Carniopharyngioma (common cause in kids) - same reason as above
- Sheehan syndrome (HY) - during pregnancy, there's high need of hormones so pituitary doubles in
size but its blood supply doesn't. Blood loss during parturition can trigger pituitary infraction.
Presents as poor lactation, loss of pubic hair (HY) and fatigue.
- Empty sella syndrome - herniation of arachnoid or pia into pituitary can damage pituitary.
Can occur congenitally too
Posterior pituitary
10. What are clinical presentation and causes of central diabetic insipidus? What is diagnosis and
treatment?
- Presentation (based on loss of free water)
Polyuria and polydipsia
Hypernatremia and high serum osmolality
Low urine osmolality and specific gravity
- Causes - damage (tumor, trauma, infection or inflammation) to hypothalamus or pituitary
Endocrine Page 1.2
15.3-15.7 Thyroid
1. Differentiate T3 and T4
T4 (thyroxine)
T3 (triiodothyronine)
T1/2 = 7 days
T4--> T3 conversion reduced in severe illness
2.
-
3. How are T3 and T4 made in thyroid gland? What is the key enzyme?
- Key enzyme is thyroid peroxidase
- Thyroglobulin are long chain of tyrosine that's stored as colloid in thyroid gland. T3/T4 are made
from it.
- Steps
Iodine is oxidized to oxidized iodine by thyroid peroxidase (oxidation step)
Oxidized iodine reacts with tyrosine to make monoiodotyrosine
Oxidized iodine reacts with monoiodotyrosine to make diiodotyrosine
The last two steps are called organification
Monoiodotyrosine + diiodotyrosine = triiodothyronine
Diiodotyrosine + diiodotyrosine = thyroxine
The last two steps are called coupling
4. What are functions of thyroid hormones?
a. Increase or decrease gene transcription by binding to nuclear receptor
b. Imp in development (Cretinism is mental retardation and dwarfism caused due to
impairment of brain and skeletal development due to hypothyroidism)
c. Increase BMR, O2 consumption and free radical formation
d. Exacerbate diabetes mellitus (increase glycogenolysis and increase hepatic gluconeogeneis)
(hyperthyroid = DM)
e. Increase LDL receptors (hyperthyroidism = low serum LDL)
f. Increase ionotropy (contractility), chronotropy (HR),
g. Increase sensitivity to catecholamine for B1 receptors(hyperthyroidism = hyperactive SANS)
h. Pulm - maintains hypoxic and hypocapnic drive (hypothyroid = hypoventilation and
respiratory arrest)
i. GI - increase gastric motility (hypothyroid= constipation, hyperthyroid = diarrhea)
j. Skeletal - increase bone reasborption and decrease bone formation (hyperthyroid =
osteopenia)
k. Neuromuscular - (hyperthyroid = increased reflex, anxiety, hyperactivity; hypothyroid =
decreased reflexes, fatigue and sluggish)
5. What causes thyroglossal duct cyst? (HY)
- Thyglossal duct is a path for descent of thyroid from tongue to its location in neck. The cyst dies
Endocrine Page 2.1
- Thyglossal duct is a path for descent of thyroid from tongue to its location in neck. The cyst dies
out normally; if it persists, it may cause cystic dilation and seen as anterior neck mass.
6. What causes lingual thyroid?
- If thyroid tissue persists at base of tongue, it's present as a mass.
Hyperthyroidism (thyrotoxicosis)
7. What are presentation of hyperthyroidism?
a. Increased basal metabolic rate (due to increased synthesis of Na/K pump) (HY) i. wt loss despite increase hunger
ii. Tremor, anxiety, insomnia, and heightened emotions
iii. Heat intolerence and sweating
b. Increased SANS (due to increased expression and activity of B1 s)
i. Cardiac - tachycardia, arrhythmia (esp in elderley)
c. Hyperglycemia (increased gluconeogenesis and glycogenolysis) (HY)
d. Hypocholesteremia and low serum LDL (increased LDL receptors) (HY)
e. Diarrhea and malabsorption (increased GI motility)
f. Osteopenia and hyercalcemia (increased bone reabsorption)
g. Decreased muscle mass and weakness
h. Oligomenorrhea
8. What is epidemiology of Grave's disease? What is it?
- Most common cause of hyperthyroidism
- Classically occurs in women of childbearing age (this group has high incidence of autoimmune
disease)
- Grave's is autoantibody IgG generation that stimulates TSH receptor leading to hyperthyroidism
(type II hypersensitivity)
9. What are clinical presentation of grave's disease?
- Diffuse goiter - TSH hormone is a trophic hormone that leads to hyperplasia and hypertrophy
- Tibial myxedema and exopthalmus
10. What causes exopthalmos and pretibial myxedema (characterstic finding) in grave's?
Fibroblast behind eye and in tibia has TSH receptors. Excitation leads to glycosaminoglycan
(chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis, and edema.
Myxedema feels like dough. And myx refers that edema is not caused by water.
11. What is histology of Grave's?
- Histology shows irregular follicle and scalloped colloid and chronic inflammation
Fig - Thyroid in grave's. Notice irregular follicles. Also, the white space between colloid and
thyroid tissue is called scalloped and is classic occurrence in Grave's.
12. What is treatment of Grave's?
- B-blockers
- Antithyroid durgs (methimazole, propylthiouracil, thyoamide) - concentrate in thyroid and block
thyroid peroxidase; also prevent T4 --> T3 conversion in peripheral tissue
- I-131 - thyroid takes it and gets destroyed (permanent hypothyroidism major complication)
- Total thyredctomy
12.5. What are lab findings in Grave's?
- Increased total and free T4
- Decreased serum TSH
- Hypocholesteremia (HY)
- Hyperglycemia (HY)
13. Differentiate thyroid storm vs myxedema coma
Thyroid storm (hyperthyroid emergency)
Myxedema coma
(hypothyroid emergency)
Presentation- mental
status change from
confusion to coma
Hypoglycemia,
hypothermia,
hypothermia,
hypoventilism
Treatment
- B-blockers, propylthiouracil, and steroids
- give Iodine salt (wolff-chaikoff block - increased iodine in
blood leads to decreased iodine uptake by thyroid and
decreased production of thyroid hormones)
14.
-
17. What's classic findings in myxedema (hypothyroidism in old kids and adults)?
a. Myxedema - classically in tongue (large tongue) and larynx (gives deep voice) (HY) - due to
increased TSH
b. Decreased BMR and decreased SANS
i. Wt. gain despite normal activity
ii. Cold intolerane and decreased sweating
iii. Bradycardia
c. Hypoventilation and respiratory arrest - thyroid maintains respiratory drive
d. Slow mental activity
e. Muscle weakness
f. Hypoglycemia, hypercholesteremia
g. Oligomenorrhea (seen in both hyper and hypothyroidism)
h. Constipation
18.
-
- Drugs (lithium)
Thyroiditis
19. What is presentation of hashimoto's thyroiditis? What chemical is is associated with? What are lab
results?
- It's an autoimmune attack to thyroid peroxidase and thyroglobulins
- Associated with HLA-DR5 (HY)
- Initially see increase T3/T4 (and low TSH) due to gland destruction. Later on, we see decreased
T3/T4 (and high TSH) due to gland destruction.
- Suspect other autoimmune disease - type 1 DM, pernicious anaemia, rheumatic disease.
- Lab results - anti TPO, anti-thyroglobulin, anti-microsomal antibodies, high TSH, low T3/T4
20. What is histologic appearance of Hashimoto's thyroditis? (HY)
- Chronic inflammation (see lymphocytes) with germinal cells.
- Presence of Hurthle cells (eosinophilic metaplasia of cells that line follicles).
Clinically mimics anaplastic carcinoma but pt are younger and usually female(in anaplastic,
pt are older)
Thyroid cancer
24. What are basics of thyroid cancer?
- Most nodules are distinct and solitary
- Most nodules are likely to be benign than malignant
25. What causes positive and negative in radioiodine uptake study?
- Positive is when thyroid takes radioiodine injected in blood - Graves, nodular goiter
- Negative - adenoma and carcinoma (do biopsy by FNA)
26.
-
Fig - follicular adenoma. Red line is the capsule that divides adenoma (bottom half) from
normal thyroid (top half)
27. What are 4 types of thyroid carcinomas (malignant stuff)?
a. Papillary carcinoma
b. Follicular carcinoma
c. Medullary carcinoma
d. Anaplastic carcinoma
28.
-
What is epidemiology, risk factor, prognosis and histologic feature of papillary carcinoma?
Most common thyroid carcinoma (80% of thyroid carcinoma)
Major risk - exposure to ionizing radiation in childhood
Prognosis - excellent even though often spreads to cervical nodes
Histology - Papillae of cells seen (so called papillary carcinoma
- Diagnosis is made by nuclear features Coffee bean nucleus (presence of nuclear groove)
Orphan eye annie nucleus (nucleus has white stuff resembling white of eye)
Psammomma bodies (concentric calcification of papillaes).
Fig - Papillary carcinoma. red circles indicate orphan eye annie nucleus. Turquoise circle
shows coffee bean nucleus.
Fig - follicular carcinoma. Red line shows the capsule and the break in it.
30.
-
Fig - MTC biopsy. All the pink stuff seen is calcitonin amyloid.
32. Describe familial cases of MTC (HY). What's significance of RET oncogene (HY)?
- Often associated with MEN 2A or 2B phenotype. (MEN = muliple endocrine neoplasia)
- MEN 2A - often see MTC, pheochromocytoma and parathyroid adenomas
Endocrine Page 2.8
33.
-
Fig - highly malignant cells in anaplastic carcinoma that don't resemble anything seen in thyroid
usually
15.8 Parathyroid
1.
-
5.
-
Constipation, peptic ulcer, acute pancreatitis (HY) - think Ca as an enzyme activator that
activates pancreatic enzymes.
Osteitis fibrosa cystica - massive reabsorption of bone leading to fibrosis and cyst
formation
- Treatment - surgery
9.
-
Secondary hyperparathyroidism
10. What are some causes for 20 hyperparathyroidism?
- Most common is chronic renal failure (HY)
Decreased phosphate excretion --> reduced free calcium in blood as most of it is bound
to phosphate ---> increased PTH production and increased bone reabsorption
11. What are lab findings in 20 hyperparathyroidism?
- Increased PTH
- Decreased serum Ca (remember that the whole process is driven by high PO4. It binds to free
serum Ca and reduces it)
- Increased serum PO4
- Increased alkaline phosphatase (increased PTH leads to increase alk phos)
Hypoparathyroidism
12. What are causes of hypoparythoroidism?
- Autoimmune
- DiGeorge syndrome (failure of develop 3rd and 4th pharyngeal pouch. Parathyroids develop
from 3rd and 4th pharyngeal pouch).
13.
-
Pseudohypoparathyroidism
14. What causes pseudohypoparathyroidism?
- Caused due to end organ resistance of PTH
- Hypocalcemia with increased PTH level (also see this is secondary hyperparathyroidism; but 20
hyperparathyroidism has increased serum phosphate levels too)
- Autosomal dominant form (mutation of Gs) associated with short stature and short 4th and
5th digit
Type 1 DM
2. Explain Type 1 DM
- Autoimmune destruction of B cells by T lymphocytes (type 4 hypersensitivity) - see inflammation
of islets
- Autoantibodies against insulin - can be seen years before disease
- Associated with HLA DR3 and DR4
3. What's presentation of type 1 DM?
- Classically seen in children
- Presentation (of insulin deficiency)
High blood glucose
Weight loss despite polyphagia (high hunger), low muscle mass - due to unopposed
catabolic action of glucagon
Polyuria, polydipsia, glycosuria
- Treatment - lifelong insulin
4. Explain mechanism of DKA (feared complication of type 1 DM)
- Excess serum ketoacids; often triggered by stress (ex-infection)
- Epinephrine increases glucagon that exacerbates lipolysis. Free fatty acids generated go to liver
and get converted to ketones.
5.
-
6.
-
Type 2 DM
7. Explain type 2 DM.
Endocrine Page 4.1
7.
-
Fig - amyloid deposition in Islets in type 2 DM. Amyloid is made of amylin - a protein
produced with insulin.
9. What is presentation and diagnosis of type 2 DM?
- Polyuria, polydipsia, hyperglycemia, often clinically silent
- Diagnosis
Random glucose (>200 mg/dl)
Fasting glucose (>126 mg/dl)
Glucose tolerance test (>200/dl two hours after glucose load)
10.
-
11.
-
12. What are two major complications of diabetes? Give examples of diseases.(HY)
- Non enzymatic glycosilation (NEG) of vascular basement membrane
NEG of large and medium vessels lead to artherosclerosis - ex - peripheral vascular disease
leading to amputation
NEG of small vessel leads to hyaline arteriolosclerosis - ex - diabetic nephropathy (nephrotic
syndrome)
NEG of hemoglobin leads to HbA1c - long term marker of glycemic control
- Osmotic damage
Endocrine Page 4.2
- Osmotic damage
Some cells in body can take sugars without insulin
Schwann cells - aldose reductase reduces glucose to sorbitol in Schwann cells. Sorbitol
leads to osmotic damage. Leads to peripheral neuropathy.
Pericytes of retinal blood vessel - sorbitol cause osmotic damage and pericytes die.
Leads to anurysm of retinal blood vessel. Rupture leads to blindness.
Lens - sorbitol build up leads to cataract.
Glucocorticoid (Cortisol)
Zona reticularis
Sex steroids
Both atrophied
Both large
Both large
8. How do you distinguish between cushing's due to ACTH made by pituitary vs pituitary made somewhere
esse (paraneoplastic)?
- Do a dexamethasone suppression test. ACTH produced by pituitary will go down but not the
paraneoplastic one.
9.
-
Adrenal insufficiency
14. What is presentation of Waterhouse-Friderichsen syndrome (acute adrenal insufficiency)?
- Commonly seen in kid with Niserria meningitis infection that causes DIC and then bilateral necrosis of
adrenal glands
- See massive hypotension
16.
-
17.
-
Fig - pheochromocytoma. Yellow parts seen in left and right are adrenal cortex.
18. What are presentation of pheochromocytoma?
- Episodic HTN, headache, palpitation
- Orthostatic hypotension may be seen - because alpha receptors are sensitized to high levels of
Endocrine Page 5.3
- Orthostatic hypotension may be seen - because alpha receptors are sensitized to high levels of
catecholamines
- Diagnosis o increased serum metanephrines
o Increased urine metanephrines and VMA
o Epi and NE are metabolized to metanephrine and normetanephrine respectively. MAO converts
both of them to VMA.
- Treatment - surgery (HY - give phenoxybenzamine (irreversible alpha 1 blocker) before surgery because
mechanical stress of adrenal can leak out epi and NE giving pt HTN and too much bleeding).
19.
-
16.1 Introduction
Presentation
Treatment
Acute
mastitis
- Erythematous breast
- Purulet nipple
discharge
- May have abscess
- Continue
drainage
- Dicloxacill
in
Periductal
mastitis
Mammary
- Chronic inflammation that causes dilation
duct ectasia (ectasia) of subareolar duct
(dialation)
1. Describe the following benign tumor and fibrocystic changes in the breast.
Epidemiology
Fibrocystic
change
Presentation
Intraductal
papilloma
2. What are the different types of fibrocystic changes and their associated breast cancer risk?
Breast cancer risk
Presentation
No increased risk
2x increased risk in
both breasts
Atypical hyperplasia
5x increased risk in
both breasts
Papillary carcinoma
Ductal
carcinoma in
situ
Histology
Mass? Remarks?
- No mass
Invasive lobular - Cells characteristically grows in single file (aka Indian file) and may show
carcinoma
signet ring morphology - cells don't make duct because they lack Ecadherin
- Usually bilateral
Fig: Small runs of invasive lobular carcinoma (arrows) with two adjacent
foci of LCIS.
3. What are the prognostic factors for breast cancer?
- TNM staging
Metastasis is most important prognostic factor but pt present early so not very useful
Spread of tumor to axillary lymph nodes (N) is most useful prognostic factor - Sentinel lymph node biopsy used to assess axillary
lymph nodes
4. What is sentinel lymph node biopsy?
- Many years before, doctors use to take out all lymph nodes in axilla to check for spread of breast cancer. In many patients, there was no
Breast Page 4.2
- Many years before, doctors use to take out all lymph nodes in axilla to check for spread of breast cancer. In many patients, there was no
spread and they had to suffer upper extremity edema due to lack of lymph nodes
- Then doctors started to inject dye in tumor and check which lymph nodes in axilla the dye moved to. If the lymph nodes with dyes didn't
had metastasis, the doctors didn't take out all the lymph nodes. If the nodes had metastasis, they would then proceed to take out all lymph
nodes. This process is called sentinel lymph node biopsy.
5. What are the predictive values of breast cancer treatment?
- Imprtant predictive values of treatment are presence of absence of overexpression of estrogen receptor (ER), progesterone receptor (PR),
and HER2/neu receptor. (HER2/neu are receptors in RAS/MAPK pathway).
Presentation
Mutations
- BRCA1- breast (medullary carcinoma - type of invasive ductal carcinoma) and ovarian carcinoma
(serous carcinoma)
- BRCA2 - breast carcinoma in males
Common type
Presentation
- Subareolar mall in older males (most breast tissue in males is in subareolar area - in females, it's in upper outer
quadrant of breast)
- May have nipple discharge
Genetic
associations
- Incomplete closure of neural tube due to folate deficiency prior to conception. Two types
Anencephaly
Spina bifida
- Types:
a. Spina bifida occulta (asymptomatic)- Vertebra is not fused because the plates of spinal arch can't
fuse because neural tube didn't close properly
- Asymptomatic; dimple of patch of hair overlying vertebral
defect
Detecti - Can be detected by elevated alpha-fetoprotein (AFP) in amniotic fluid and maternal blood.
- AFP most abundant protein in young fetus blood (albumin of fetus) - made by fetal liver and yolk sac.
on
- AFP elevated in other cases too - hepatocellular carcinoma, liver metastasis, yolk sac tumor, germ cell tumor.
Anatom - Neural plate invaginates early in gestation to make neural tube
- Walls of neural tube - makes CNS
y
- Hollow lumen of neural tube - makes ventricles and spinal cord canal
- Neural crest - makes peripheral nervous system
Defn
- Stenosis of cerebral aqueduct (of sylvius) - connects 3rd and 4th ventricles; leads to
hydrocephalous
- CSF is made by choroid plexus lining the ventricles
Epid
- CSF leaks from 4th ventricle to subarachnoid space via foramen of Magendie
(middle) and foramen of Luschka (lateral)
Dandy walker malformation
Defn
Arnold-Chiari malformation
Defn
Seringomyelia
Defn
- Cystic degeneration of spinal cord usually on C8-T1 that affects the spinothalamic
(anteriolateral) pathway and later on affects anterior horn (motor neurons) and
lateral horn (SANS)
- Typically spares dorsal column pathway (fine touch and position)
Presentati - Sensory loss of pain and temperature in upper extremities and 'cape like'
on
distribution (anterior white commissure of spinothalamic tract)
- Muscle atrophy and weakness (anterior horn damage)
- Horner's (lateral horn - hypothalamospinal tract damage)
Poliomyelitis
Defn
Cause
Pathophys - Frataxin gene imp for mitochondrial iron regulation; loss results in iron buildup with
free radical damage
Presentati - Loss of multiple spinal tracts:
on
Loss of vibration and proprioception
Muscle weakness in lower extremities
Loss of deep tendon reflex
- Presents in early childhood; pt are wheelchair bound in few years
17.3 Meningitis
Defn
Cause
- Lumbar puncture
SC ends at L2; put needle between L4 and L5 - level of iliac crest; cauda equina
continues to S2
CSF findings
Cells
Bacteria Neutrophils
Glucose Protein
Low
Virus
Lymphocytes Normal ?
Fungal
Lymphocytes Low
Stroke
Epdm
Types
- Regional ischemia that causes focal neurological defects lasting >24 hours
- If symptoms last <24 hours, it's called transient ischemic attack (TIA)
Thrombotic
Cause
Embolic
Lacunar
- Due to hyaline
arteriolosclerosis
(complication of HTN
and diabetes)
ion
infraction
- If internal capsule
involved --> pure motor
stroke
- If thalamus involved -->
pure sensory stroke
1-3 days
- Neutrophil infiltration
3-7 days
- Microglial infiltration
2-3 weeks
HEMORRHAGIC STROKE
Intracerebral hemorrhage
Defn
- Bleeding to subarachnoid space (blood vessels are outside pia but inside the arachnoid layer)
Presentation
Cause
17.5 Trauma
Subdural hematoma
Defn
Cause
- Herniation
- Herniation
Tonsilar herniation
Subfalcine herniation
Uncal herniation
- Cerebellar tonsils
herniates under
foramen magnum
- Cingulate gyrus
herniates under falx
cerebri
Presenta - Compression of
- Compression of
tion
brainstem can lead to anterior cerebral
cardiopulmonary
artery leads to
arrest
infraction
Leukodystrophy
Defn
Epid
Genetics
Diagnosis
Imaging
1.
Alzhimers
2. What is clinical presentation of Alzhimer's (no. 1 cause of dementia)?
Begins with short term memory loss and then long term memory loss
Loss of motor skills and language
Change in behavior and personality
Pt become mute and bed ridden; infection is common cause of death
Focal neurologic defect in late stage
Fig: Neuritic plaques (left) and neurofibrillary tangles (tau tangle) on right
5. How are A-beta (AB) amyloid plaques formed?
AB amyloid is made from amyloid precursor protein (APP) encoded by chromosome 21. If APP
undergoes beta cleavage instead of normal alpha cleavage, AB amyloid is fomed.
AB amyloid formation increases due to mutation in APP or trisomy 21.
Fig: C is caudate (makes head that ends at lateral ventricle floor), P is putame. C+P = striatum
(called striatum because there's stripe running in between C and P).
Fig: Cross section of huntington's pt brain showing small caudate that leads to hydrocephalus ex
vaculo (hydrocephalous due to loss of brain mass)
15. What is presentation of huntington's disease?
Average age of presentation: 40
Presents with chorea and progresses to dementia and depression
16. What is common cause of death in huntington's disease?
Suicide
Normal pressure hydrocephalous
17. What is presentation of normal pressure hydrocephalous? How can you improve symptoms?
Can causes dementia (idiopathically)
Increased CSF leading to dilation of ventricles - causes stretching of corona radiata (nerve fibers
runing at side of ventricles).
3 W's caused due to stretching of corona radiata wet (urinary incontinence)
Wobbly (gait disturbance)
Wacky (personality changes)
Symptoms improve with lumbar puncture. Treatment is VP shunt (ventricle-peritoneum shunt)
Spongiform encephalopathy
18. What is pathophysiology of spongiform encephalopathy?
PrPc is normal CNS protein which is in alpha helical structure. It's converted to PrPsc which is in
beta pleated shape.
PrPsc is congo red +ve (amyloid).
PrPsc is resistant to damage by autoclave or sterilization or by proteases. Also, it can convert other
PrPc to PrPsc.
19. What are biopsy findings in spongiform encephalopathy?
Intracellular vacuoles (called spongiform changes)
Kid (infratentorial)
Astrocytes
Oligodendrocytes
- Oligodendroglioma (M)
- Ependymoma (M)
Neurons
Meninges
- Craniopharyngeoma (B)
B = benign; M = malignant
Adult tumors
1. Glioblastoma multiforme (GBM)
Defn
Epid.
Fig: butterfly glioma (left); pseudopallisading tumor cells (middle); GFAP stain on right
Prognosis
2. Oligodendroglioma
Defn
3. Meningioma
Defn
Epid.
Presentation - Histology:
Whorled pattern of cells
Psammoma bodies may be present
- Seen as round mass attached to dura on imaging - can cause seizure by compression
Cause
Features - If present within the cranium, most frequently involves CN 8 (presents as loss of hearing and tinnitus)
- Tumor cells S-100 +ve
1. Pilocytic astrocytoma
Defn
Epid.
2. Ependymoma
Defn
Presentati - Biopsy:
on
perivascular pseudorosette is characteristic (pseudorosette because the central structure isnt
part of the tumor. Originally, pseudorosette meant any rosette that didnt have a truly empty
lumen)
True ependymal rosette - rosette with central lumen as tumor's attempt to make CSF
- Tumor can result in hydorcephalous
Fig: bottom right- perivascular pseudorosette; top left: true ependymal rosette .
3. Medullobastoma
Defn
Presentation - Histology:
Homer-Wright rosettes may be present (type of true rosette)
Small, round, blue cells on biopsy
Prognosis
- Poor; tumor rapidly grows and spreads via CSF giving 'drop metastasis in cauda equina
4. Craniopharyngioma
Defn
- Benign tumor that arises from epidermal remnant of Rathke's pouch (makes parts of pituitary
gland)
Presentation - Supratentorial mass in child or young adult (only supratentorial kid tumor we study)
- Can cause bitemporal hemianopsia due to compression of optic chiasm
- Calcifications can be seen - derived from 'teeth like' tissue
Source
Virtigo
minutes)
age old male with PMH of ..... presents with .... most concerning with...
Presen.
Osteopetrosis (bone-that-is-like-stone)
Defn
- Poor osteoclast function leading to abnormally thick and heavy bone that fractures
Musculoskeletal Page 1.1
Defn
- Poor osteoclast function leading to abnormally thick and heavy bone that fractures
easily like a piece of chalk
Pathophy - Multiple pathways but one is mutation in carbonic anhydrase II that leads to loss of
s.
acidic microenviroment required for bone reabsorption
Presen.
- Bone fractures
- Anemia, thrombocytopenia, leukopenia with extramedullary hematopoiesis - due to
bony replacement of marrow (myelophthisic process)
- Hepatosplenomegaly - extramedullary hematopoiesis
- Vision and hearing impairment - due to impingement of cranial nerves
- Hydrocephalous - due to narrowing of foramen magnum
- Renal tubular acidosis - seen if carbonic anhydrase mutation present; CA important
for tubular reabsorption of HCO3- in tubules
Vit D
biochem
Vit D
function
Picmonic
Picmonic
- Reduction of bone density due to loss of trabecular (spongy) bone that increases risk
of fracture
Risk
- Risk based on peak bone mass (attained ~30 years) and rate of bone loss after that
- Peak bone mass depends on genetics (Vit D receptor variation), diet and exercise
- Rate of bone loss is <1% per year after that. Bone loss increases due to lack of
exercise (space travel), poor diet and lack of estrogen
Clinic.
features
- thick, sclerotic bone that fractures easily due to imbalance between osteoblast and
osteoclast activity; first osteoclast overactive, then both equal activity, then
osteoblast overactive.
Epid
- Mostly seen in >60 year olds (most common cause of isolated increase in alk
phosphate in >40 year olds)
Etiology
Clinic
features
Types
Causes
- Staph aurues
- Neisseria gonorrhoeae
- Salmonella
- Pseudomonas
- Pasteurella
Causes
Benign tumors
Osteoma
Chondroma - Divided as enchondroma (seen on medulla, mainly on small bones of hand and feet) or juxtacortical
chondroma (seen on bone surface)
- Benign tumor of osteoblast with osteoid core (radiolucent) most commonly seen on diaphysis
- Size <2cm
- Localized pain, most severe at night, is an almost universal complaint
- Pain is relieved by asprin
Size >2cm
Pain not relieved by asprin
Osteochond - Most common benign tumor of bone
roma
- Tumor of bone with overlying cartilage cap; arises from lateral part of metaphysis and bone is
contineous with marrow space
- Overlying cartilage can rarely transform to chondrosarcoma
Giant cell
tumor
Malignant tumors
Osteosarco
ma
Defn
- Malignant tumor of osteoblast that has two peak incidence - most common in teenagers,
then in elderly
Risk
factors
- Familial retinoblastoma
- Paget disease (during the osteolbastic hyperactivity phase)
- Radiation exposure
Presentati - Occurs mostly in metaphysis of long bones (distal femur or proximal tibia mainly)
on
- Imaging shows destructive mass with 'sunbrust' appearance due to periosteal reaction
and lifting of periosteum by adjacent tumor(codman triangle)
Chondrosa - Malignant tumor of cartilage seen in medulla that can grow out through cortex to make sessile
rcoma
paracortical mass
- Seen mostly in central skeleton or pelvis
Ewing
sarcoma
Defn
- Small round blue cells that resemble lymphocytes (can be confused with lymphoma or
chronic osteomyelitis) (presence of homer wright rosettes indicate neural differentiation)
Cause
- Often associated with 11;22 translocation (ewing sarcoma gene (EWS) on ch 22 merges
with transcripton factor gene; precise pathophys unknown)
Musculoskeletal Page 2.3
Malignant
tumors
18.3 Joint
DJD
RA
Spondyloarthropathy
Risk factors
- Obesity
- Age
- Trauma
Clinical
features
Pathologic
features
Fig: from left to right - characterstic fibrillation of articular cartilage; 1=bone eburnation, 2
=subchondral cyst, 3 = normal articular cartilate; joint mice; osteophytes
Fig - osteophytes leading to heubordin-bouchard notes on the left x-ray. Right is normal hand xray
Rheumatoid arthritis
Defn
- chronic systemic autoimmune joint disease that causes symmetrical polyarthritis and mainly
Musculoskeletal Page 3.1
Defn
- chronic systemic autoimmune joint disease that causes symmetrical polyarthritis and mainly
affects PIP and MCP joints
- Classically seen in middle age woman
Genetics
Complicaio - Anaemia ns
chronic inflammatory state produces hepsydin (acute phase protein). Hepsydin blocks ability
to use iron that's stored in macrophage. Results in anemia
- Secondary amyloidosis (liver makes acute phase protein SAA that gets converted to AA amyloid
deposition)
Seronegative Spondyloarthropathy
7. What are clinical features of spondyloarthropathy? Explain its types.
- Negative rheumatoid factor (aka seronegative)
- Affects axial skeleton
- Associated with HLA-B27
- Types
Ankylosing spondyloarthritis
Seen in young adult males
Presents with sacroiliitis and ankylosis of spine (bamboospine)
Uveitis - eye inflammation
Aortitis (weak aorta can lead to aortic regurgitation)
Reiter syndrome (reactive arthritis)
Can't see (conjuctivitis)
Can't pee (urethritis - pains with urination)
Can't climb tree (arthritis)
Usually seen in young males a week after GI or C trachomatis infection.
Psoriatic arthritis
Affects 10% of psoriatic patients
Affects axial and peripheral joints
Affects DIP of hands and feet (leads to sausage finger and toes) (HY)
Infectious arthritis
Most commonly seen with Neisseria gonorrhea (young adults)
Staph aureus (old people or kids).
Pt usually have only one joint affected - only the knee
Musculoskeletal Page 3.2
Dearmatomyositis vs polymysosits
Dermatomyositis
Polymyositis
Defn
Cause
Lab
Biopsy
- Degenerative disease with muscle wasting due to bad dystrophin protein and replacement of
muscle by fat
dystrophin gene
- Presents as proximal muscle weakness at 1 year age; distal
muscles involved later
Calf pseudohypertrophy characteristic finding (filled
with fat)
- Death due to cardiac or respiratory failure; myocardium
commonly involved
Neuromuscular junction
Myasthenia gravis vs Lambert-Eaton syndrome
Myasthenia gravis
Lambert-Eaton syndrome
Defn
Pt popn
Lipoma
Liposarcoma
Fig: Top left - arrow points to scalloped nucleus in liposacoma; bottom left scalloped definition; right - normal adipose tissue biopsy
Rhabdomyoma - Benign tumor of skeletal muscle
- Cardiac rhabdomyoma is associated with tuberous sclerosis
Rhabdomyosarc - Malignant tumor of skeletal muscle
- Most common soft tissue tumor in children
oma
- Rhabdomyoblast is characterstic cell - desmin positive
- Most common site is eyes, head and neck; vagina is classic site in young girls
Character
Stratum basalis
Statum spinosum
INFLAMMATORY DERMATOSES
Atopic dermatitis and contact dermatitis
1. Differentiate atopic dermatitis and contact dermatitis.
Atopic dermatitis
Contact dermatitis
Same presentation
and edema
- Type I hypersensitivity reaction; associated with
asthma and allergic rhinitis
- Usually start in face in infancy; seen mostly on
flexor surface afterwards
Acne vulgaris
Presentation - Comedones (whitehead and blackheads), pustules, and nodules
- Very common in adolescents
Cause
Psoriasis
Presentation
Histology
Treatment
- Corticosteroids
- UV-A light with psoralen
- Immune modulating therapy
Lichen planus
Presentation - Pruritic, purple papules with reticular white lines on surface (wickham striae)
- Commonly seen on wrists, elbow, and oral mucosa
Histology
Etiology
- Unknown
- Associated with Hep C infection
Bullous pemphigoid
Linear immunofluorescence
Histology -
Presentation
Nikolky sign
- Potentially fatal
Immunofluorec Fish net immunofluorescence pattern- IgG surrounding keratinocytes
ence
Presentaiton
Immunofluoresce
nce
Dermatitis herpetiformis
Cause
Association
Treatment
Cause
Stevens-Johnson
syndrome (SJS)
Toxic epidermal
necrolysis
Cause
Histology
Leser-Trelat
sign
Acanthosis nigricans
Presentation - Epidermal hyperplasia with symmetric darkening of skin (velvet like skin)
- Often presents in axilla, neck, groin
Association
Epidemi
ology
Risk
Progres
sion
Histolog
y
Treatm - Excision
ent
- Metastasis is uncommon
- Excision
- Metastasis is uncommon
- Keratoacanthoma - well differentiated SCC that develops rapidly and regress spontaneously;
presents as cup shaped tumor filled with keratin debris
Basal layer
Albinism
Freckle
- Localized loss of
skin
pigmentation
- Due to
autoimmune
damage of
melanocytes
Mesalma
- Mass like
hyperpigmentation of
cheeks
- Congenital enzyme
defect (tyrosinase) of
melanin production
pathway
- May involve eyes only
or eye and skin
Prognosis
- Most common acquired nevi appear in early childhood; evaluate lesions after 20
years age
- Nevi changes is normal. Ex - hormones, pregnancy
- Dysplasia is precursor to melanoma
Melanoma
Definition
Epidemiology - Significant risk of metastasis (contrast to basal cell carcinoma and SCC of skin)
Skin pathology Page 4.1
Epidemiology - Significant risk of metastasis (contrast to basal cell carcinoma and SCC of skin)
Risk
Growth types - Radial - horizontal growth across epidermis; low risk for metastasis
- Vertical - growth to deep dermis
Depth of extension (Breslow thickness) most important prognostic factor
for metastasis
Genetics
Often associated with BRAF V600E kinase mutation (55% of cases) (HY)
Treatment
Variant of
Skin pathology Page 4.2
Variant of
melanoma
Superficial spreading
Nodular
Acral lentiginous
Cellulitis
Presentati - Erythematous macules that progress to - Red, tender, swollen rash with fever
on
pustules; rupture of pustules causes
honey crusted skin
Cause
Pathophysiology
Molluscum contagiosum
Presentation - Firm, pink, umbilicated papules
Cause
- Poxvirus infection
Histology
Classic pt
- Kids
- Sexually active adults
- Immunecompromised individuals
Dermatologic morphology