Block B Path

Front 1

Rubella

Back 1

1. Maternal disease causing congenital heart disease
2. PATENT DUCTUS ARTERIOSUS- causes a left to right shunt
3. cataracts
4. microcephaly

Front 2

Teratogenic drugs causing congenital heart disease

Back 2

1. antimetabolites
2. thalidomide
3. trypan blue

Front 3

Cytogenic defects causing congenital heart disease

Back 3

1. Down's - trisomy 21
2. Turners syndrom - XO

Front 4

Down's Syndrome - Congenital Heart Disease

Back 4

1. increased ostium primum defects (ASD)
2. endocardial cushion defects
3. higher risk of common A-V canal

Front 5

Turner's syndrome - Congenital HEart Disease

Back 5

coarctation of the aorta

Front 6

Etiologic agents that cause Congenital Heart Disease

Back 6

1. maternal disease - Rubella
2. Teratogenic drugs
3. Genetics
- cytogenic defects
- single gene defects
4. environmental

Front 7

high altitude and congenital heart defect

Back 7

risk of a patent ductus arteriosus for people born at high altitudes

Front 8

septation defects

Back 8

when the walls between the atria or ventricles fail to develop normally resulting in ASD or VSD

Front 9

Rotation defects

Back 9

great vessels do not rotate properly and therefore do not fit properly

Front 10

endocardial cushion defects

Back 10

1. can lead to obstructions or abnormal communications

2. Types
a. stenosis, coarctation
b. VSD
c. Common A-V canal
d. Malformed valves
e. Truncus arteriosus

Front 11

Aortic Arch Defects

Back 11

1. persistence of the aortic arches that normally disappear

2. defects where persistence of arches form a network of vessels around structures of the neck – vascular rings

Front 12

Left to Right Shunt

Back 12

1. produces chronic right-sided overload
2. leads to right sided cardiac enlargement with pulmonary hypertension and pulmonary artery dilatation

Front 13

Ventricular Septal Defect

Back 13

1. most frequent type of congenital heart disease
2. most common site for VSD is high in the septum in the area of the membranous septum, which is part of the endocardial cushions

Front 14

ostium primum ASDs

Back 14

defined as low lying atrial septal defect within:
1. intact ventricular septum
2. separate atrioventricular valve rings

usually a cleft in the aortic leaflet of the mitral valve associated with abnormal chordae tendineae

occasionally a cleft in the septal leaflet of the tricuspid valve

Front 15

Lutembacher's syndrome

Back 15

1. ASD + mitral stenosis
2. exaggerated left to right shunt

Front 16

ASD types

Back 16

1. ostium primum
2. Lutembacher's syndrome
3. Common Atrioventricular Canal

Front 17

Common atrioventricular canal
(persistent atrioventricularis communis)

Back 17

1. endocardial cushion failure with an exaggerated ASD

2. involves a high VSD where the AV valves do not meet and instead form a large ring around AV valve area
3. MOST COMMONLY FOUND IN DOWN'S SYNDROME

Front 18

Patent Ductus Arteriosus

Back 18

Left to right shunt

Ductus areteriosus remains open long after birth

abnormal communication between the pulmonary artery and the aorta

etiology: Rubella and high altitude

Front 19

Heart Defects without Shunt or Cyanosis

Back 19

1. pulmonary stenosis
2. coarctation of the aorta

Front 20

pulmonary stenosis

Back 20

1. hypertrophy of RV
2. increased pressure in right atrium
3. increased pressure in RA may cause foramen ovale to remain open --> causing right to left shunt

Front 21

Coarctation of the aorta

Back 21

narrowing and constriction of the aorta

Front 22

Coarctation of the aorta - infantile form

Back 22

1. called pre-ductal tubular hypoplasia
2. occurs proximal to the origin of the ductus arteriosus
3. not compatible with life
4. the only blood that enters the systemic circulation passes from the pulmonary artery through the ductus arteriosus but this blood is not oxygenated causing cyanosis in these tissues

Front 23

adult coarctation - post ductal

Back 23

1. constriction occurs distal to the origin of ductus arteriosis
2. due to precence of collaterl circulation, is compatible with life
3. blood pressure will be significantly higher in the upper extremeities than lower

Front 24

Common clinical features of cyanotic heart disease

Back 24

1. clear lung fields
2. polycythemia
3. cyanosis
4. clubbing of fingers

Front 25

Tetralogy of Fallot

Back 25

Most common cause of cyanotic heart disease

Made up of 4 Components
1. High ventricular septal defect
2. pulmonary stenosis
3. dextroposed aorta (Overriding aorta)
4. Right Ventricular Hypertropy

Front 26

Blalock-Taussig surgery

Back 26

1. creates an artifical ductus arteriosus

2. a branch from subclavian is hooked up to the aorta
- allows poorly oxygenated blood coming from the aorta to go to the lungs to get oxygenated
- creates a left to right shunt

Front 27

Tricuspid atresia

Back 27

1. valve is absent - blood is unable to flow from right atrium to right ventricle

2. blood is shunted through foramen ovale and the lung is supplied by collateral flow

3. patent ductus ateriosus is needed to get oxygenated blood

Front 28

Transposition of the great vessles

Back 28

caused by failure of the spetum to form normally

Front 29

Taussig-Bing Heart

Back 29

(1) complete transposition of the great vessels with (2) pulmonary artery overriding a VSD

Front 30

Truncus arteriosus

Back 30

common trunk fails to divide into aorta and pulmonary artery during development

often assocated with septal defects

Front 31

Cor Trilocular Biatriatum

Back 31

two atria w/ a single ventricle

frog heart

Hint 31

frog heart

Front 32

Hypoplastic left ventricle

Back 32

mitral and aortic atresia

Failure of the left side of the heart to develop

Front 33

Eisenmenger’s syndrome

Back 33

Congenital Heart Disease with cyanosis developing later in life

a. is similar to Tetralogy of Fallot but without pulmonary stenosis

Front 34

Causes of reversal of left to right shunts

Back 34

long-standing ductus arteriosus

long standing atrial septal defects

Front 35

Complications of congenital Heart Disease

Back 35

Failure to thrive
mental retardation
Fatigue
Bacterial Endocarditis
brain abscess - due to right to left shunts
cyanosis - which will lead to polycythemia which increases chance of arterial thrombus
hypoxia

Front 36

Epstein's anomaly

Back 36

downward displacement of the tricuspid valve

Front 37

Complications that can occur to an atherosclerotic lesion

Back 37

1. hemorrage into the lesion
2. thrombosis superimposed on the lesion
3. degeneration of the media beneath the intimal lesion

Front 38

hallmarks of atherosclerosis

Back 38

1. intimal lesion
2. characterized by the accumulation of fat

Front 39

ateriosclerosis

Back 39

thickening, fibrosis, hyalinization, and narrowing of arterioles with HTN

some arterioles are more predisposed than others --> most frequently in the kidney

Front 40

Clinical significance of Atherosclerosis

Back 40

1. main underlying cause of coronary heart disease
2. sets stage for occulsion
3.weakening of the media --> aneurysm
4. thrombi can form upon these plaques --> emboli

Front 41

atherosclerosis as a precurosor of cardiovascular disease

Back 41

1. underlying cause of 95% of CHD (coronary heart disease)
2. cause of most casese of most common form of stroke (atherothrombotic cerebral infarct)
3. cause of peripheral vascular disease
4. direct cause of most ABDOMINAL aortic aneurysms

Front 42

HTN (interrelated with Atherosclerosis)

Back 42

1. HTN is one of big 4 risk factors for CHD
2. HTN is aggravating factor for most major forms of stroke
3. key to intracerebral hemorrage
4. Accelerates atherosclerosis and arteriolar sclerosis throughout the body

Front 43

Atherosclerosis
(arteries involved)

Back 43

1. large elastic arteries
2. medium sized muscular

Front 44

Atherosclerosis
(accumulations)

Back 44

1. connective tissues
2. various blood products
3. lipids

Front 45

Moncckenberg's Sclerosis
(arteries involved)

Back 45

1. muscular arteries
2. arteries of the extremities --> the radial artery

Front 46

angina pectoris

Back 46

coronary arteries are stenotic or occluded

Front 47

most common form of stroke

Back 47

atherothrombotic cerebral infarction

Front 48

Endothelial dysfunction and activation manifestations

Back 48

1. increased endothelial permeabilty
2. enhanced leukocyte adhesion
3. alterations and expression of a number of endothelial gene products

Front 49

Right to Left Shunts

Back 49

1. Tetralogy of Fallot
2. Tricuspid atresia
3. Transposition of the great vessels
4. Taussig-Bing heart
5. Truncus arteriosus
6. Total anomalous pulmonary venous return

Front 50

Causes of Cyanosis Later in Life

Back 50

Eisenmerger’s Syndrome
long standing PDA
long standing ASD

Front 51

Left to Right Shunts

Back 51

1. VSD
2. ASD
3. PDA

Front 52

Transmural MI

Back 52

1. solid
2. distribution of narrowed or occluded coronary artery
3. may lead to shock
4. pericarditis frequent; fibrinous usually
5. may result in aneurysm

Front 53

Subendocardial MI

Back 53

1. Patch
2. Circumfrential: inner 1/3 of myocardium
3. often result of shock
4. No pericarditis
5. no aneurysm formation

Front 54

Hyperthyroidism

Back 54

1. increased heart rate
2. decreased perfusion

Front 55

Catecholamines

Back 55

can cause coronary artery spasm

Front 56

Rt. Coronary artery distribution

Back 56

1. posterior left ventricle
2. posterior interventricular septum

Front 57

Lt. Anterior descending artery distribution

Back 57

1. anterior left ventricle
2. anterseptal myocardium
3. apex of left ventricle

Front 58

Circumflex coronary artery distribution

Back 58

lateral wall of left ventricle

Front 59

Complications of MI

Back 59

1. contractile dysfunctions
2. arrhythmias
3. myocardial rupture
4. Pericarditis
5. Mural thrombus with or without embolus
6. Ventricular aneurysm

Front 60

Stable angina

Back 60

associated with underlying atherosclerotic lesion

Front 61

Unstable angina

Back 61

associated with ruptured plaque or superimposed thrombus

Front 62

Prinzmetal angina

Back 62

associated with vasospasm

Front 63

Ischemic Heart Disease risk factors

Back 63

Major
1. hyperlipidemia
2. hypertension
3. smoking

Minor
1. Diabetes
2. Gout
3. Obesity
4. Type A Personality

Front 64

Aortic arch defects

Back 64

a. persistence of the aortic arches that normally disappear
b. double arches
c. defects where persistence of arches form a network of vessels around structures of the neck – vascular rings

Front 65

Myocarditis

Back 65

inflammation of the myocardium

presents with symptoms similar to cardiac failure

Front 66

Inflammation of mycocarditis

Back 66

1. results in elevated cardiac enzymes
2. can be due to viral causes

Front 67

Viral Myocarditis

Back 67

1. short acute inflammatory phase
2. striking mononuclear phase
3. eosinophilic myocarditis
4. lipofuscin present
5. survivors will often have fibrosis scattered through the myocardium

Front 68

eosinophilic myocarditis

Back 68

numerous eosinophils in viral myocarditis

Front 69

Giant Cell Myocarditis

Back 69

1. idiopathic
2. numerous giant cells and a mononuclear infiltrate

Front 70

Infectious Endocarditis

Back 70

1. due to bacterial infection that can embolize to the coronary system and cause abscess in the myocardium

2. called septic myocarditis

3. can be caused by sepsis or bacteremia

Front 71

Cardiomyopathy

Back 71

1. caused by concentric or eccentric hypertrophy

2. Three types
a. dilated cardiomyopathy
b. hypertrophic cardiomyopathy
c. restrictive cardiomyopathy

Front 72

Dilated cardiomyopathy

Back 72

1. most are idiopathic
- can be casued by chronic alcoholism, chemotherapy, postpartum

2. eccentric hypertrophy

3. Results in systolic dysfunction as the floppy walls can’t pump out enough blood; the walls are susceptible to mural thrombi

4. Classic finding is a dilated heart

Hint 72

EDucation = eccentric hypertrophy for dilated cardiomyopathy

alcohol causes decreased contraction --> dilates

Front 73

Hypertrophic cardiomyopathy

Back 73

1. also called Idiopathic Hypertrophic Subaortic Stenosis (IHSS)

2. Results in an increased septal wall thickness while the free wall maintains its normal thickness.

3. There is disorder of the myocardial fibers

4. Diastolic dysfunction with a high ejection fraction, but low volume --> due to poor ventricular filling

5. Patients have
a. exertional dyspnea,
b. harsh systolic ejection murmur,
c. and mural thrombi


6. Common cause of sudden death in young athletes

Hint 73

muscles hypertrophy in young athletes --> common cause of sudden death

poor filling because of increased septal wall thickness --> not enough blood can get in

Front 74

Restrictive Cardiomyopathy

Back 74

1. usually affects both ventricles; sometimes atria

2. diastolic dysfunction

3. Results in Dyspnea, fatigue, CHF

4. caused by RASH
a. amyloid
b. sarcoid
c.hemochromatosis
d. radiation

5. Results in:
a. endomyocardial fibrosis
b. loffler endomyocarditis
c. endocardial fibroelastosis

Front 75

Endomyocardial Fibrosis

Back 75

ventricular fibrosis seen in sub-Saharan African children

Front 76

Loffler endomyocarditis

Back 76

fibrosis in adults with reactive or neoplastic eosinophilia

Front 77

Endocardial Fibroelastosis

Back 77

Left ventricular fibrosis in kids with congenital heart disease

Front 78

Right Ventricular hypertrophy

Back 78

1. it’s an abnormal communication between the right and left ventricles

2. usually caused by a lung problem

Front 79

Hypertension
(results in)

Back 79

1. Results in:
a. cardiomegaly
b. left ventricular hypertrophy
c. myocyte hypertrophy

Front 80

Findings in hypertrophy as a reflection of hypertension

Back 80

1. hyalin or hyperplastic arteriolosclerosis

Front 81

HTN is a risk factor for

Back 81

1. atherosclerosis
2. Renal failure
3. Granular kidneys
4. Hypertrophied heart
5. Hypertension hemmorage in brain

Front 82

Arteritis biospy shows

Back 82

i. Inflammation in the walls of arteries
ii. Inflammatory cells
iii. Giant cells
iv. Thrombi
v. Elastic disruption

Front 83

Takayusu Arteritis

Back 83

1. affects aorta and large arteries --> subclavian and carotids

2. get granulomatous arteritis with fibrosis and vessel narrowing

3. idiopathic

4. sen in younger people

5. sometimes get a pulseless disease where you have no pulse in one arm, but a pulse in the other

Hint 83

True Love
1. heart skips a beat --> pulselessness

2.Large arteries --> aorta and carotids and subclavian

3. seen in young people--> young love

Front 84

Temporal(Giant Cell) arteritis

Back 84

1. affects muscular arteries --> temporal, opthalmic, and cranial arteries

2. results from destruction of elastic fiber in the intima and media; giant cells come in an eat up the elastin scraps

3. symptoms
a. visual changes
b. head aches
c. occasionally you get thrombi

4. can often palpate a nodule in superficial temporal artery

5. affects elderly people; very rare to see this before age 50

Front 85

Poly arteritis Nodosa

Back 85

1. affects muscular arteries --> those of GI tract, mesentery, liver, gallbladder, pancreas, and muscle

2. lots of fibrinoid necrosis

3. iodiopathic, but can be immunological

4. affects all layers of the vessel with a fibrinoid necrosis and periarterial inflammation

Front 86

Kawasaki's Arteritis

Back 86

1. leading cause of acquired heart disease in children

2. affects arteries in kids

3. presents with
a. fever and lymphadenopathy --> like a viral infection
b. rash on feet
c. edema
d. cardiac anomalies

3. looks like polyarteritis nodosa early on

4. later on results in coronary aneuryms--> usually self limiting

Front 87

Wegner’s Granulomatous Arteritis

Back 87

a. Affects small arteries and veins esp. those of the lungs, kidneys, and upper respiratory tract

b. Acute necrotizing vasculitis with fibrinoid necrosis of the vessel wall proximal to the granuloma

c. Usually along the midline

Front 88

Hypersensitivity Angitis

Back 88

a. Affects small vessels, capillaries, and arterioles in all organs and tissues

b. Results in an acute necrotizing vasculitis of the entire wall

c. Often result in thrombi

Front 89

Buerger’s Arteritis

Back 89

a. Affects young male smokers

b. Affects the arteries veins and nerves of the extremities, esp. the lower extremity

c. unlike diabetic or atherosclerotic vasculitis, this one hurts

d. Can get microabcesses, acute inflammatory reaction penetrating the arterial wall, but the underlying architecture is preserved.

e. Will eventually go away after cessation of smoking

Front 90

Syphilitic (leutic) Aneurysms

Back 90

1. Results from tertiary syphilis-rarer now than in the past; usually tertiary syphilis kills patients now

2. Affects the ascending aorta and the aortic arch

3. Destruction of the media following endarteritis obliterans
a. Destroys the elastic fibers and causes the aorta to bulge out

4. Grossly shows irregular wrinkling of the aorta early on, called tree marking

5. Can often involve the aortic ring which will lead to aortic valvular insufficiency

Front 91

Atherosclerotic aneurysms

Back 91

1. Usually occur in the abdominal aorta, can sometimes occur in the common iliacs, rarely in the thoracic aorta

Front 92

Dissecting hematomas

Back 92

1. another word for ruptured aneurysm

2. not usually tied to dilatation

3. cystic medial degeneration is part of the pathogenesis - seen in Marfan's

4. results in intimal tears in 85-90% of cases

5. types A and B

6. of results from hypertension

7 patients will complain of a tearing sensation in their back

Front 93

Dissecting hematomas Type A

Back 93

involves the ascending aorta

1. Important because it usually ruptures into the pericardium and you get hemopericardium, cardiac tamponade, and death

Front 94

Dissecting hematomas Type B

Back 94

does not involve the ascending aorta

1. May rupture into the peritoneum, pleura, or back into the aorta (double barrel aorta)

Front 95

Berry Aneurysm

Back 95

A. Usually occurs at bifurcation of the cerebral arteries in the Circle of Willis

B. Is a discontinuity of the smooth muscle of the media at the point of bifurcation

C. Can result in a subarachnoid hemorrhage

Front 96

Mycotic Aneurysm

Back 96

A. An infection arteritis

B. Occurs secondary to a direct invasion of the bacteria or fungi into the vessel

C. Wall weakens because of inflammation and you get the aneurysm

Front 97

Ventricular aneurysm

Back 97

A. Occurs secondarily to myocardial ischemia

B. Mostly affects the coronary arteries

Front 98

Ischemic heart disease causes

Back 98

1. diminshed blood supply
2. increased oxygen demand
3. decreased oxgyen availability

Front 99

Causes of increased oxygen demand

Back 99

1. hypertension - can cause hypoxic changes in the myocardium
2. valvular stenosis with/without insufficiency
3. Hyperthyroidism - increases heart rate
4. catecholamines

Hint 99

hvhc

Front 100

Categories of Ishcemic Heart Disease

Back 100

1. Angina Pectoris
2. Sudden Cardiac Death
3. Chronic Ischemic Heart Disease with Failure
4. Myocardial Infarct

Front 101

end results of Rheumatic Fever

Back 101

thickening and fusion of the mitral valve

Front 102

common myeloid stem cell

Back 102

1. develops into
eosinophils
neutrophils
basophils
macrophages
platelets
erythrocytes

Front 103

common lymphoid stem cells

Back 103

develop into
B cells
T cells
NK cells

Front 104

B cells

Back 104

1. located in follicles of lymph node

Front 105

T cells

Back 105

located deep to the follicle in the paracortex

Front 106

sinusoids

Back 106

1. located outside the follicles and beneath the fibrous capsule where the lymphatics empty into

2. lined by histiocytes

Front 107

plasma cells

Back 107

loacted deeper in the medullary cords of the lymph node

Front 108

tingible body macrophages

Back 108

macrophages that have phagocytosed something

large clear cells within follicles or germinal centers

Front 109

Evaluation of LAD (lymphadenopathy)

Back 109

1. size
2. pain/tenderness
3. Consistency
4. location

Front 110

LAD Pain/Tenderness

Back 110

1. usually indicates an inflammatory process

2. malignancy could present with pain if there is any necrosis or hemorrhage involved

3. Tenderness is not a reliable method to differentiate benign from malignant

Front 111

LAD consistency

Back 111

1. Firm or hard nodes
- are generally associated with malignant tumors and often metastatic

2. Soft nodes
- are normally found with inflammatory or infectious processes

3. Suppurant
- means contain pus
- often termed fluctuant which means rubery

4. Shotty
- term describing small nodes felt just beneath the skin that resembles the feel of a buckshot
- ofthen seen in children with viral infections

5. Matted
- series of enlarged nodes that seem connected and often move as a unit
- may be benign, sarcoid, or associated with malignancy

Front 112

Cat Scratch Disease

Back 112

enlarged cervical/axillary nodes after being scratched by a cat on the extremity

Front 113

Age and enlarged supraclavicular lymphadenopathy

Back 113

1. in population over 40, there is a 90% chance this is malignant

2. under 40 --> risk drops to 25%

Front 114

Acute Nonspecific Lymphadenitis

Back 114

1. reaction to UNKNOWN microbial agents

2. most often cervical due to oral cavity/pharynx infections
- also found in inguinal nodes due to injury of lower extremeties

3. nodes are tender, fluctuant, and the overlying skin is reddened

4. see a collection of neutrophils

5. nodes are rarely biospsied because can be identified with a good history

Front 115

Chronic Nonspecific Lymphadenitis

Back 115

1. when nodes remain enlarged for extended periods of time with no known etiologic agent

2. frequently biopsied and one of three conditions is often revealed
a. follicular hyperplasia
b. paracortical lymphoid hyperplasia
c. Sinus Histiocytosis

Front 116

Follicular hyperplasia

Back 116

1. occurs when exciting Ag stimulates B cells

2. preservation of lymphnode architecture --> so benign
- well defined germinal centers
- tingible body Macrophages

3. presence of dark/light zones within the follicle

4. hallmark feature of this condition is the precense of an eccentric cuff of lymphocytes or polarized mantle zone

5. often seen in patients with early HIV, Rheumatoid arthritis, toxoplasmosis

Front 117

Paracortical lymphoid Hyperplasia

Back 117

1. exciting Ag stimulates T cells

2. often seen with reactions to drugs or viral infections

3. NO preservation of lymph node architecture

4. hypertrophy of sunusoidal endothelial cells

Front 118

Sinus histiocytosis

Back 118

1. high levels of phagocytosis by large histiocytes that line the sinusoids

2. seen in lymph nodes that are draining areas of cancer
- most often found in axillary nodes in a patient who has undergone a mastectomy
- Histiocytes proliferate as they are being presented with tumor antigen

3. Not much germinal center activity or lymphocytes left, but marked proliferation of histiocytes.

Front 119

aleukemic leukemia

Back 119

normal WBC or perhaps even lower WBCs but their bone marrow has been replaced by enlarged multiple blasts

Front 120

Characteristics of Lymphoid Neoplasms

Back 120

1. ALL primary neoplasms of lymph nodes are MALIGNANT

2. Divided into two categories: Hodgkin and non-Hodgkin Lymphoma

3. Disorders range from being indolent (chronic disease where the patient can survive a long time) to very aggressive in behavior
- Indolent lymphomas can acquire further mutations and transform into a more aggressive type

4. Majority (80-85%) are of B cell origin

5. All derived from a single cell that became malignant -they are MONOCLONAL

Front 121

Lymphoid Neoplasms Treatment and prognosis basis

Back 121

a. Dominant cell type and its biologic behavior (indolent vs. aggressive)
b. Stage of disease (extent of spread)
c. Underlying health of the patient separate from the malignant lymphoma

Front 122

Lymphoma Classifications

Back 122

1. Rapparpot Classification
- based solely on light microscopy

2. WHO classification
- based on morphology, cytogenetics, molecular markers

Front 123

WHO lymphoid Neoplasm Classification

Back 123

1. Non Hodgkin Lymphomas
- further divided into:
a. B-cell neoplasms
b. T- and NK-cell neoplasms

2. Hodgkin Lymphoma

Front 124

Hodgkin Lymphoma

Back 124

1. will begin in a single group of nodes and then orderly spread to the next adjacent chain of lymph nodes

2. Rarely involves Mesenteric nodes and Waldeyr's tonsillar ring

3. Extranodal involvement is uncommon (but be aware that it can occur)

4. Primarily treated with radiation and chemotherapy is only used in widespread disease

Hint 124

hodgkin are more limited.... not extranodal, begin as a single group of nodes, spread adjacently

Front 125

2. Non-Hodgkin Lymphoma

Back 125

a. Frequently involves multiple sites of lymph nodes

b. Spread is noncontiguous, that is it may spread from the neck to the inguinal nodes without any indication of disease between the two

c. Mesenteric and Waldeyer’s ring are commonly involved

d. Extra-nodal involvement is common

e. Radiation has little use and chemotherapy must be used
i. These patients often have widespread disease at the time of diagnosis

Front 126

WHO’s Classification of B Cell Neoplasms

Back 126

1. Precursor B Cell Neoplasms
2. Mature B Cell Neoplasms

Front 127

Precursor B Cell Neoplasms

Back 127

a. Can be either a leukemia or lymphoma but most seen in patients are leukemias

b. This includes acute lymphoblastic leukemia (leukemia of childhood)

Front 128

Mature B Cell Neoplasms

Back 128

a. Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL)
i. Involve the same cell but named according to where disease process starts

Front 129

amalgam

Back 129

1. a silver-containing material for cavity fillings

2. if it gets incorporated into the tissue, the silver darkens and loos like a black macule
-resembles a melanoma
-gets biopsied often

Front 130

Tooth Formation

Back 130

1. teeth start forming in the embryo as early as 6 weeks

2. teeth are derived from ectoderm

3. at birth, the crowns of teeth are formed

4. 20 baby teeth - 5 per quadrant

5. At 6 months of age, the incisors come in (usually the lower ones erupt first).

6. By age 2, all of the teeth except molars are present, though the crown of the first molar is starting to erupt. While this is happening, permanent teeth are forming

7. All 20 baby teeth will be replaced by permanent teeth, plus there will be an additional 3 molars behind the baby teeth in each of the 4 quadrants of the mouth. Thus, there is a total of 32 permanent teeth

8. At the age of 6 years, front baby teeth start to fall out & get replaced by permanent teeth - 1st permanent teeth begin to erupt

9. The 2 baby molars are replaced in the adult by premolars/bicuspids.

10. Around the age of 12, the 2nd permanent molars come in.


11. The 3rd and final molars (“wisdom teeth”) come in around age 18,

Front 131

tooth bud

Back 131

an invagination of the oral ectoderm into the surrounding mesoderm

2. becomes a tooth and starts to calcify, beginning at the top

Front 132

Crown

Back 132

1. predominantly enamel, which is ectodermally-derived

2. mineralizes first and extends downward to the root

Front 133

Root

Back 133

made mostly of dentin

Front 134

dentin

Back 134

1. can be made throughout life, BUT ENAMEL CANNOT

2. makes up most of the root

3. is more like bone because it's organic and has a matrix (unlike enamel)

Front 135

Fully- formed Tooth

Back 135

1. Enamel covers the crown and ends at the junction with the gums

2. beneath the enamel is dentin

3. Peridontal ligament is the outer layer that connects the tooth root to the bone

4. collagen fibers from bone are inserted into this layer to anchor the root to the bone

Front 136

Enamel

Back 136

mostly mineralized

Front 137

Peridontal ligament

Back 137

outer layer that connects the tooth root to the bone

Front 138

Dental caries

Back 138

1. caused by Streptococcus mutans

2. oraganisms break down carbohydrates from the diet and produce lactic acid that demineralizaes teeth.

3. S. Mutans is able to live in the acid

4. when it gets into dentin, it tends to spread laterally

Front 139

pulp

Back 139

1. consists of nerves and blood vessels that come in from the apical foramen

2.untreated streptococcus mutans can extend all the way into the pulp

Front 140

pulpitis

Back 140

toothache

infection that reached the pulp

Front 141

periapical granuloma

Back 141

1. cyst

2. pulpitis that extends through the apical foramen

3. cysts are epithelial lined structures
-Epithelial remnants from tooth formation are left behind and proliferate in response to inflammation, resulting in a cyst

Front 142

xanthogranulomas

Back 142

lots of macrophages and cholesterol-containing foam cells,

Front 143

Causes of tooth loss
(most common first)

Back 143

1. normal shedding of baby teeth that are then replaced by permanent teeth.

2. Dental caries are the most common PATHOLOGICAL cause of tooth loss

3. Extraction by dentists

Front 144

orocutaneous fistula

Back 144

an infection in the MOLARS that extended through the apical foramen in the root, through the mandibular bone, into the adjacent tissue, and through the skin

Front 145

Peridontal Disease

Back 145

1. Periodontitis - inflammation of the gums surrounding teeth

2. With severe & rapidly progressive types of this disease, there is likely to be an underlying immune problem (e.g., AIDS

Front 146

gingiva

Back 146

oral mucosa that invests teeth and overlies bone

Front 147

hyperplasia of the gingiva

Back 147

1. predisposition caused by food particles collected around the teeth & formed plaques

2. enlarged and red

3. happened in diabetic patient on the slide

4. promoted by the drug Dilantin

Front 148

acute necrotizing ulcerative gingivitis

Back 148

1. caused by spirochete & fusiform organisms in the mouth

2. Immunosuppressed patients are susceptible to this

3. necrosis of the gingiva between the teeth

4. pink gingiva
is flat because it underwent necrosis

Front 149

stomatitis

Back 149

swelling & inflammation of the mouth

Front 150

Reactive lesions

Back 150

1. pseudotumors in the oral cavity called “fibromas” are actually just fibrous hyperplasia

2. secondary to trauma usually

3. the most common biopsies that oral pathologists see

Front 151

Types of Reactive lesions

Back 151

1. pyogenic granuloma
2. Giant Cell granulomas

Front 152

pyogenic granuloma

Back 152

1. a collection of granulation-type tissue that is very vascular

2. arises from the mucosa

3. Pregnant women & kids in puberty are at higher risk for this lesion due to hormonal changes

4. somewhat polypoid and the surface of this lesion often ulcerates

Front 153

Giant Cell Granulomas

Back 153

1. vascular & rust-colored due to hemosiderin-laden macrophages

Front 154

Brown Tumor

Back 154

1. developed by patients with hyperparathyroidism which usually affects bone

2. looks just like giant cell granulomas

Front 155

herpetic gingivostomatitis

Back 155

1. ulceration of the gingiva & oral mucosa

2. caused by an acute infectiion of herpes simplex virus (HSV) type I in childhood

3. A smear of a lesion reveals polykaryon cells with multiple nuclei & central clearing

4. pateints suffer from fever, lethargy, loss of appetite, & lymphadenopathy, and usually recover in about 3 weeks.

5. HSV enters the trigeminal ganglia and becomes latent

Front 156

Uclers

Back 156

1. fairly common and not very significant, but can be associated with a more serious disease

2. Types
a. minor aphthous ulcer
b. Major aphthous ulcers

Front 157

minor aphthous ulcer

Back 157

1. no organism associated with these lesions.

2. They are thought to be due to T cell cytotoxicity, which occurs when there is a change in the CD4:CD8 ratio

3. seem to occur in times of stress or after trauma

4. patients can be given tetracycline or steriods

Front 158

Major aphthous ulcers

Back 158

1. a lot bigger and last a lot longer than minor aphthous ulcers, but less common

2. seen more often in the elderly

Front 159

Systemic diseases associated with uclers

Back 159

1. stomatitis
2. Inflammatory bowel disease
3. intestinal lymphoma - also associated with aphtous ulcers

Front 160

mucosal fold

Back 160

seen with chron's disease

Front 161

granulomas

Back 161

related to bowel disease

Front 162

Hutchinson incisors

Back 162

1. screwdriver shaped” incisors

2. associated with congenital syphilis
a. At the time of birth, the permanent incisors have already started to develop. If a fetus contracts syphilis, then in the 3rd trimester it interferes with the development of the incisors.
b. 6-year molars also begin developing in the 3rd trimester, so those teeth can be malformed too.

Front 163

candidiasis

Back 163

1. can be contracted in the mothers birth canal

2. types
a. torus palatinus
b. angular stomatitis

Front 164

Torus Palatinus

Back 164

a hard overgrowth (developmental anomaly) in the midline of the palate.

Front 165

angular stomatitis

Back 165

1. type of candidiasis

2. involves in the corners of the mouth

3. people who don't have teeth are predisposed to this

Front 166

leukoplakia

Back 166

adherent white plaques or patches on the mucous membranes of the oral cavity

Front 167

Stomatitis nicotina

Back 167

1. type of leukoplakia

2. seen in smokers and tobacco chewers

3. NOT considered a pre-malignant lesion

4. hard palate is a common site for this but not SCC
- soft palate is a high risk area for SCC

Front 168

high-risk areas for oral cancer.

Back 168

the lateral tongue,
floor of the mouth,
& soft palate

Front 169

Oral areas less associated with cancer

Back 169

The hard palate,
gingiva,
& buccal mucosa

Front 170

Erythroplakia

Back 170

1. a flat red patch or lesion on the mouth

2. is more likely to be malignant than leukoplakia

3. Probably near 80% of these lesions will show carcinoma in situ or invasive cancer (vs. somewhere near 20% for leukoplakia

Front 171

Carcinoma of the tongue

Back 171

1. has about a 50% overall survival rate

2. may metastasize to cervical lymph nodes and the lungs

3. Sometimes it is called “hairy tongue,” because of the extension of filiform papillae.

Front 172

Spindle cell carcinoma of oral cavity

Back 172

1. more malignant type of SCC

2. consists of elongated spindle-shaped cells
- (look like sarcoma cells), but they are actually squamous cells

Front 173

Verrucous carcinoma of Oral Cavity

Back 173

1. a type of SCC in the mouth

2. may begin as leukoplakic lesions

3. looks like warts.

4. It can spread through the mouth, especially the mucosa

5. is more indolent & slow-growing than spindle cell carcinoma

Front 174

Cysts

Back 174

viral (e.g., adenovirus) or allergic-type processes

Front 175

Tumors in the sinuses

Back 175

A. Carcinoma
B. Lymphoma
C. Plasmacytoma

Front 176

Tumors in Larynx

Back 176

A. Laryngitis
B. Laryngeal carcinoma
- seen on the true vocal cords, which consist of squamous cells
- 50% survival rate

Front 177

Tumors in ear

Back 177

1. Outer ear
- Sun exposure can lead to squamous cell carcinoma and basal cell carcinoma

2. Middle Ear
- squamous cell carcinoma --> a more serious condition

Front 178

nasopharynx

Back 178

1. site of inflammatory processes due to viruses

Front 179

Repeated bouts of inflammation can lead to hyperplasia of tissues in the upper airway and edema.

Back 179

can lead to the formation of polyps that obstruct orifices (e.g., antrum), and this in turn increases the susceptibility to infection (e.g., sinusitis).

Front 180

hairy leukoplakia

Back 180

Epstein-Barr virus):

often along the lateral border of the tongue; oral manifestation of systemic disease seen in immunocompromised patients

Front 181

aphthous ulcers

Back 181

ulceration covered by a thin exudate and rimmed by a narrow zone of erythema

Front 182

Dentigerous Cyst

Back 182

1. cyst that forms around the crown of unerupted tooth

2. frequently the the third molar

3.second most common jaw cyst

4. makes bone weak and susceptible to fracture upon trauma

5. Treatment - cysts are removed and tooth is take out

6. seen in people in late 20s

7. cyst is a stratified squamous-lined structure - usually associated with inflammation

Front 183

dental root-end cyst

Back 183

most common jaw cyst

Front 184

odontogenic keratocyst

Back 184

1. has specific appearance

2. pallisading basal cell layer, 5 cells thick with corrugated (wavy) surface

3. gets bigger and has a higher rate of recurrence than other cysts

Front 185

Gorlin syndrome

Back 185

1. multi system Autosomal dominant disorder

2. characteristic nevoid basal cell carcinoma

3. can include multiple lesions including
- ovarian fibromas,
- bifid ribs,
- changes on palms of hands

Front 186

Ameloblastoma
(adults)

Back 186

1. usually benign tumor of jaw bone that can produce deformation of the bone

2. A true neoplasm of basaloid cells that rarely shows metastasis

3. More often in the mandible, but tumors in the maxilla can extend up into the cranium

4. Treatment - surgery
- high recurrence rate if the tumor is not taken out completely

5. Tumor tends to be cystic and multilocular

Front 187

Ameloblastoma
(kids - under 20)

Back 187

1. more “treacherous” because it is unilocular cyst

2. and looks more like a dentigerous cyst.
- So if you treat it as a dentigerous cyst, it can cause a lot of destruction to bone

Front 188

Odontoma

Back 188

1. probably Hamartomas of tooth tissue

2. surrounded by follicle

3. most common dental tumor

4. can be associated with other tumors, such as ameloblastomas

Front 189

Nasal Polyp

Back 189

A. Can occur as a result of repeated inflammation/chronic infection of the nasal cavities and sinuses

B. Can obstruct airways and lead to bacterial infection

C. Microscopic slide shows:
1. a lot of eosinophils, lymphocytes,
2. the normal pseudostratified ciliated columnar epithelium,
3. and lots of edema due to chronic infection of the airways

Front 190

Nasopharyngeal Angiofibroma

Back 190

1. very Vascular; it can look like erectile tissue

2. Can cause nose bleeds (epistaxis) and blood loss

3. very big locally and cause destruction of tissue

4. common in adolescent boys

Front 191

Inverted Papilloma

Back 191

1. finger-like projections are directed inward, into the tissue
- Normally a papilloma is a warty extension from a surface epithelium into a lumen

2. usually arise from the lateral nasal wall

3. can get very big and have a high recurrence potential

4. have important potential to develop into carcinoma

Front 192

Carcinoma of Maxillary Sinus

Back 192

swelling on the side of his face (reaching the eye)

2. include
- squamous cell carinoma,
- lymphoma,
- and plasmacytomas
a. histologically malignant, but rarely go on to multiple myeloma

Front 193

Nasopharyngeal Carcinoma
(types)

Back 193

1. Keratinizing squamous cell nasopharyngeal carcinoma
2. Non-Keratinizing squamous cell nasopharyngeal carcinoma
3. Undifferentiating squamous cell nasopharyngeal carcinoma

4. neoplasms can metastize while still very small,

Front 194

Undifferentiating cell nasopharyngeal carcinoma

Back 194

1. malignant cells are epithelial cells that are very undifferentiated, very pale, light pink, vesicular, and they have micronucleoli

2. radio-sensitive tumors so they can be treated effectively with X-ray therapy

3. associated with Epstein Barr Virus

Front 195

Things associated with Epstein Barr Virus

Back 195

mononucleosis,
hairy leukoplakia,
Brukitt’s lymphoma,
inflammatory pseudotumor of spleen,
Undifferentiating cell nasopharyngeal carcinoma

Front 196

Squamous cells carcinomas on the larynx

Back 196

A. Risk factors: smoking and drinking
B. Results in persistent hoarseness
C. Behaves like other squamous cell carcinomas, but has a better prognosis

Front 197

Angioinvasive T cell lymphoma

Back 197

1. thought to be due to NK T cell lymphoma

2. blood vessel undergoing necrosis with large atypical basophilic lymphoid cells in the surrounding area (the necrotic vessel is in the middle of the slide)

3. can result in Mid-Face Necrotizing Disease

Front 198

Conditions that can result in Mid-Face Necrotizing Disease

Back 198

Angioinvasive T cell lymphoma

Wegener’s granulomatosis,

EBV,

or fungal infections; in particular mucormycosis in a diabetic

Front 199

Necrotizing Sialometaplasia

Back 199

A. This condition is benign

B. It also causes necrotizing lesions in the midline; patient may say, “The roof of my mouth fell out”

C. results in metaplasia of salivary ducts into squamous cells. See invasion of squamous cells, remember this is particular condition is not cancerous (it can be mis-diagnosed as cancer)

D. This is self-healing, so you will not need to treat it

Front 200

Thyroglossal Duct Cyst

Back 200

1. While the thyroid begins development at the base of the tongue and migrates down the midline, cysts can develop anywhere along this tract (including the lips)

2. Microscopically this will show squamous or respiratory-type epithelial lining and perhaps lymphoid tissue or thyroid tissue in it

3. Be very cautious about removing this cyst because a patient may have an ectopic thyroid on the posterior tongue, called a lingual thyroid, and you do not want to remove their only thyroid tissue!

Front 201

Periganglioma Carotid Body Tumor

Back 201

A. Occurs in the bifurcation of the carotid
B. Also called chemodectoma
C. This tumor is parasympathetic (whereas its counterpart in the adrenal medulla produces sympathetic catecholamines)

D. Microscopically you will see “endocrine appearance,” which shows capillaries outlining masses of homogenous cells

E. these tumros are unpredictable- their behavior cannot be predicted based on their histology

Front 202

Cholesteatoma

Back 202

A. Cyst that develops in the middle ear from chronic ear infections (chronic otitis media)

B. Characterized by proliferation of squamous epithelium and development of lots of keratin

C. These can be extensive and cause destruction

D. Misnomer because it does not usually contain cholesterol, but it can be locally destructive

Front 203

Sialoliths/Salivary Stone

Back 203

A. Located in the mouth where salivary duct and submandibular gland come out (under tongue)
B. Can cause gland obstruction which leads to inflammation of the gland, called sialadenitis

Front 204

Salivary Mucocele

Back 204

Usually due to trauma to the mucosa in which the salivary duct is severed.

Mucus leaks into the surrounding tissue and causes an inflammatory reaction, resulting in a lesion called a mucocele

common in children

Front 205

Ranula

Back 205

mucocele of the floor of the mouth

Front 206

Sjögren’s Syndrome

Back 206

A. Autoimmune disease where salivary glands, lacrimal glands, and parotid glands are destroyed by lymphocytes
B. Lose protection of saliva resulting in dental carries even around the necks of teeth (where they normally do not occur)
C. Symptoms: Difficulty swallowing, Dry eyes, Dry mouth, Swollen parotid glands (see bilateral enlargement in photo)
D. If you biopsy the lactrimal or parotid glands, you will see a “sea” of lymphocytes replacing the acini
E. These patients are candidates for malignant lymphoma
F. Diagnostic tool: Schirmer test measures amount of tear production in the eye

Front 207

Keratoconjunctivitis Sicca

Back 207

Sjögren’s Syndrome when not associated with another autoimmune disease

Front 208

Tumor of the Parotid Gland

Back 208

Most salivary gland tumors occur in the superficial parotid gland

Front 209

Warthin tumor

Back 209

Papillary Cystadenoma Lymphomatosum

1. Only seen in parotid gland, which is the most common site for salivary tumors
2. Occurs more often in men
3. 8% of the time found bilaterally (see unilateral swollen side of face in photo)
4. Benign condition
5. LYN: Epithelium is similar to ductal epithelium but appears bright red with a lot of mitochondria. These epithelial cells are called oncocytes. It has papillary formations and a prominent lymphoid tissue component

Front 210

Acinic Cell Carcinoma

Back 210

1. another type of salivary tumor

2. can present in multiple sites

3. This can be in parotid or submandibular gland and contains cells that have serous granules like in the parotid gland

Front 211

Pleomorphic Adenoma/Mixed Tumor

Back 211

1. Most common gland tumor

2. most often found in the parotid gland - but can be found in any other gland in the mouth

3. Thought to originate from myoepithelium contractile cells of the ductal structures

4. Produces many different types of tissue (for example, cartilage is seen)

5. Typically have a capsule

6. These tumors are benign

Front 212

Intraoral Salivary Tumors

Back 212

a. Palate (off of the midline) is most common site for oral tumors

b. Inside the mouth, salivary tumors are more likely to be malignant than those occurring in the parotid gland

Front 213

Pleomorphic Adenocarcinoma

Back 213

1. Microscopically looks like squamous cell

2. Over a short time, cancer developed and grew quickly

Front 214

Mucoepidermoid Tumor

Back 214

A. The most common malignant salivary gland tumor

B. composed of mucin producing and squamous or epidermoid cells

C. Low grade tumors tend to be cystic with less of the squamous component, good prognosis

D. High grade tumors tend to be more solid (less cystic) with more squamous components, fewer mucin cells, more mitoses visible, more necrosis; not so good prognosis

Front 215

Adenoid Cystic Carcinoma

Back 215

A. The third most common malignant salivary gland tumor

B. Very low-growing malignant tumors that tend to grow up nerves and get very large

C. They were previously thought to be benign because they grow very slowly

D. Microscopically shows peculiar net-like pattern with dark cells in between
1. These can have a more tubular appearance as well

Front 216

ACP (amorphous calcium phosphate)

Back 216

1. Supposed to prevent caries in mouth
2. Supposed to produce re-mineralization of enamel (like fluoride which can reverse small lesions in enamel)

Front 217

Time is Tooth

Back 217

1. This just means that the more quickly you can get treatment for a knocked out tooth, the more likely you are to have healing/restoration

2. If a child’s tooth is knocked out, first try to set it back in its socket and pad with gauze, or in the gutter of the mouth (if the child won’t swallow it). Otherwise, put it in cold milk and get to the dentist!
1. If the tooth is “cemented” back into place within 30 minutes-1 hour it might “take”

Front 218

require antibiotic prophylaxis

Back 218

Having an artificial valve or a history of infective endocarditis

MITRAL VALVE PROLAPSE DO NOT REQUIRE PROPHYLAXIS

Front 219

Bisphosphonates

Back 219

1. relieves symptoms of osteoperosis or multiple myloma

2. cause severe necrotic procsses in the jaw

Front 220

Upper esophageal sphincter

Back 220

1. located at the level of cricopharyngeus muscle; at the cricoid cartilage

2. Most common site of foreign body impaction (70%) is at the UES

Front 221

Aortic arch crossover

Back 221

1. in the middle esophagus

2. 15% of foreign bodies become lodged in the mid esophagus

Front 222

Lower esophageal sphincter (LES):

Back 222

1. where the esophagus crosses the diaphragm

2. 15% of foreign bodies become lodged at the LES

Front 223

Esophagus
(Anatomical Consideration)

Back 223

1. three narrow points
a. UES
b. Aortic arch cross over
c. LES

2. Muscularis propria of the proximal esophagus contains striated muscle

3. throacic esophagus lacks a serosa

Front 224

Muscularis propria of proximal esophagus

Back 224

contains striated from the cricopharyngeus
- explain why skeletal muslce disorders can cause esophageal dysfunction

Front 225

thoracic esophagus and lack of a serosa

Back 225

1. outermost connective tissue layer lacks a mesothelial lining and is called adventitia

2. this facilitates the rapid dissemination of infections and tumors into the mediastinum

Front 226

Esophageal Congenital anomalies

Back 226

1. Agenesis
2. Atresia
3. Stenosis
4. Duplications

Front 227

Esophageal Agenesis

Back 227

it never formed

Front 228

Esophageal Atresia

Back 228

1. lack of canalizatoin of a segment of the esophagus

2. most common contains a proximal blind pouch connected to the pharynx and a lower pouch leading to the stomach
a. Usually associated with a fistula connecting the esophagus (lower or upper pouch) with a bronchus or the trachea
b. In most cases (87%) there is a blind proximal esophageal segment (from the mouth) and a fistula connecting the distal (to the stomach) segment with the trachea or mainstem bronchus

3. usually at the level of the tracheal bifurcation

4. Complications
a. food aspiration
b. suffocation
c. pneumonia

5. other congenital anomalies are present in 50% of infants with esophageal atresia

Front 229

Esophageal Stenosis

Back 229

1. narrowing or stricture of the esophageal lumen
- fibrous thickening of the esophageal wall (particularly the submucosa with atrophy of the muscularis propria

2. Results in progressive dysphagia (difficulty swallowing);
- first to solids then to solids and liquids

3. More commonly acquired than congenital

Hint 229

think like stenosis of the arteries and valves --> IT's PROGRESSIVE

Front 230

Acquired esophgeal stenosis

Back 230

1. Peptic - 70 to 80% of all cases; caused by GERD

2. Pill esophagitis (Drug/pill induced)- potassium chloride, ferrous sulfate, aspirin (NSAIDS), tetracycline, quinidine, ascorbic acid, bisphosphonates

3. Complications of radiation therapy, sclerotherapy (injection of a sclerosing agent into esophageal varices), nasogastric intubation, esophagoscopy

4. Caustic - ingestion of caustics such as lye (strong alkali)

5. Connective tissue disorders - especially scleroderma

6. tumors

Front 231

Esophageal Duplications

Back 231

1. double esophagus, two lumens

2. two types
a. closed
b. open

3. Present as masses usually in the lower esophagus (60%)

4. Diagnosis is often early in childhood with

5. Digestive symptoms: dysphagia, vomiting, and failure to thrive

6. Respiratory symptoms due to reflux: dyspnea, wheezing, and coughing spells

Front 232

Closed esophageal duplications

Back 232

1. closed at both ends - duplication cyst
- most common presentation

2. usually in lower portion of the esophagus

Front 233

Open esophageal duplications

Back 233

1. Open at ONE end (giant diverticulum)

2. Open at BOTH ends (double esophagus)

Front 234

Esophageal Webs

Back 234

1. ridge like mucosal protrusions into the esophageal lumen; not circumferential

2. Semicircumferential or eccentric,

3. usually occur in the upper/cervical esophagus

4. More frequent in women over age 40

5. May cause dysphagia to solids

Hint 234

think of spiders --> they're webs are high up, and they catch solid things

think of charolette's web--> spider was female

Front 235

Esophageal Webs - Etiology

Back 235

1. uncertain
- some probably congenital
- some associated with Plummer-Vinson Syndrome

Hint 235

plumbers get webs of hair out of the drain

Front 236

Plummer- Vinson Syndrome

Back 236

1. Also called the Paterson-Brown Kelly syndrome or sideropenic dysphagia

2. Characterized by an upper esophageal web, dysphagia, and iron deficiency anemia (sideropenia)

3. Occurs mostly in women

4. May have an autoimmune etiology or may occur in association with autoimmune diseases

5. Other components [14]
• Cheilosis—angular stomatitis • Atrophic glossitis—• Koilonychias—• Achlorhydia—

6. Risk for squamous cell carcinoma in the upper/cricopharyngeal region of the esophagus (hypopharynx and proximal esophagus)

7. May respond to iron supplementation or balloon dilatation

Front 237

Cheilosis

Back 237

angular stomatitis; inflammation at the corners of the mouth

Front 238

Atrophic glossitis

Back 238

inflamed, flattened, and enlarged tongue

Front 239

Koilonychias

Back 239

abnormal concavities of fingernails and toenails; “spoon nails

Front 240

Achlorhydia

Back 240

lack of hydrochloric acid from gastric juice; lack of gastric acidity

Front 241

Rings (Schatzki ring)

Back 241

1. circumferential (diaphragm-like) mucosal protrusions
- Concentric plates of tissue protruding into the lumen of the distal esophagus

2. Occur in the lower esophagus; thicker then webs

3. No sex predilection - no sexual preference

4. Most patients are older then 40

5. Etiology uncertain
a. Some probably congenital
b. Some may be associated with GERD
c. Some associated with medications that induce esophagitis and stenosis

6. May cause dysphagia to solids

Hint 241

both rings and webs cause dysphagia to solids

Front 242

Achalasia

Back 242

1. Failure to relax

2. Characterized by:
a. increased resting tone of LES
b. incomplete relaxation after swallowing
c. absent of defective peristalsis

2. characteristics cause progressive dilatation of the esophagus leading to megaesophagus

3. Two types
a. primary
b. secondary

4. results in a FUNCTIONAL DISORDER
a. fluctuant (fluctating) dysphagia for solids and liquids
b. regurgitation, nocturnal coughing spells
c. aspiration of food

5. risk for squamous cell carcinoma

Front 243

primary Achalasia

Back 243

most cases are idiopathic

Front 244

Secondary Achalasia

Back 244

1. caused by damage to the myenteric pelxus

2. Occurs with:
a. Chagas disease (Trypanosoma cruzi; prevalent in South America) *
b. Diabetic neuropathy*
c. Amyloidosis
d. Sarcoidosis
* only ones mentioned in class

Front 245

Hiatal hernia

Back 245

1. herniation of the stomach through the esophageal hiatus

2. characterized by separation of the diaphgragmatic crura and widening of the space between the muscular crura and esophageal wall

3. may be congenital or acquired

Front 246

Acquired hiatal hernias are secondary to:

Back 246

1. Muscle weakness, aging (prevalence increases with age)

2. Increased abdominal pressure
a. Central obesity, pregnancy (due to the pressure from the pregnancy itself and/or progesterone levels), constipation

3. Can cause or can be caused by GERD
a. Esophageal shortening (associated with GERD inducing fibrosis and repair) can cause a hernia
b. Hernia disrupts the LES mechanism inducing GERD

Front 247

Two major types of hiatal hernia

Back 247

1. sliding (Axial) hernia

2. Paraesophgeal (rolling, non axial) hernia

Front 248

Sliding (axial) hernia

Back 248

1. the esophagus slides together with the stomach in the same axis

2. Protrusion of the stomach above the diaphragm creates a bell-shaped dilation, bounded below by the diaphragmatic narrowing

3. 90% or more of hiatal hernia cases

4. Most are asymptomatic

5. Some associated with GERD symptoms and ulcers on the lesser curvature where the diaphragm impinges on the stomach (Cameron ulcers)

Front 249

Paraesophageal (rolling, nonaxial) hernia

Back 249

1. stomach rolls/protrudes alongside the esophagus
a. A separate portion of the stomach (usually along the greater curvature) enters the thorax through the widened foramen

2. Most are symptomatic
i. Dysphagia, postprandial discomfort,(after eating) dyspnea

3. Susceptible to gastric volvulus (twisting/rotating) and strangulation can occur

4. Early surgical repair is recommended

Front 250

Gut Diverticula

Back 250

A. Outpouching or envagination of the gut anywhere in the intestine

B. Classified as
1. “True” or congenital diverticula: contain all visceral layers in the protrusion (mucosa, submucosa, muscularis propria, etc.); example is the Meckel diverticulum in the ileum; rare
2. “False” or acquired diverticula: contain only mucosa and submucosa; they project through the muscularis propria; most esophageal and gastrointestinal diverticula

Front 251

Esophageal Diverticula

Back 251

1. Zenker diverticulum

2. Traction diverticulum

3. Epiphrenic diverticulum

* may develop in the 3 parts of the esophagus

Front 252

Zenker diverticulum

Back 252

1. located immediately above the UES
i. Herniation between thyrophargyngeus and cricophyrangeus

2. Also called a pharyngoesophageal diverticulum

3. May be caused by incomplete relaxation of the UES

4. Results in:
• Sensation of mass in the neck
• Regurgitation of undigested food (spontaneously or by applying pressure externally on the neck)
• Risk of aspiration
• Halitosis—bad breath

Front 253

Traction diverticulum

Back 253

1. near the midpoint of the esophagus

2. May be caused by scarring/fibrosis resulting from mediastinal lymphadenitis
- this is caused by TB and histoplasmosis
(as with tuberculosis and histoplasmosis lymphadenitis)

3. Usually asymptomatic

Front 254

Epiphrenic diverticulum

Back 254

1. immediately above the LES; point where esophagus crosses the diaphragm

2. May be caused by esophageal spasm or hypertensive LES

3. May result in regurgitation

Hint 254

phrenic nerve causes spasms... and innervates the diaphragm --> LES

Front 255

Esophageal Lacerations

Back 255

1. Mallory-Weiss tear

2. Boerhaave syndrome

Front 256

Mallory-Weiss tear

Back 256

1. Non-transmural (mucosal) laceration/tears at esophagogastric junction or gastric cardia
- it affects the mucosa only

2. Superficial tear

3. Associated with persistent forceful retching (following an alcoholic binge)
- classically described after an alocoholic binge --> because you puke

4. Life threatening hematemesis --> most lethal complication

Front 257

Boerhaave syndrome

Back 257

1. Transmural rupture/perforation of the esophagus following forceful emesis

2. Tear goes all the way through the esophagus (esophageal rupture)

3. Causes severe hematemesis, shock, mediastinitis, and sepsis

4. High mortality (35%)

5. Considered the most lethal perforation of the GI tract

Front 258

Esophageal Varices

Back 258

1. Varicose dilatation of mucosal and submucosal veins; tortuous dilated veins

2. Mostly caused by portal hypertension
a. Portal blood flow is diverted through the gastric coronary veins and into the esophageal plexus

3. Rupture causes massive hematemesis; bleed has been associated with high mortality

4. Re-bleeding occurs frequently

5. Treatment advances has substantially improved the outcomes of these patients
i. Banding—ligation with plastic bands
ii. Sclerotherapy—injection with thrombotic agents
iii. Embolization
iv. Balloon tamponade—inflatable balloon positioned in the lumen of the esophagus
v. Portosystemic shunts—communication surgically created between the portal vein and the systemic circulation to alleviate portal hypertension

6. Varices develop in 90% of cirrhotic patients and are most often associated with alcoholic cirrhosis

Front 259

Esophagitis

Back 259

1. inflammation of the esophageal mucosa

2. High prevalence

3. GERD

Front 260

GERD

Back 260

1. reflux esophagitis

2. Excessive reflux of
i. Stomach contents (acid reflux)
ii. Duodenal contents (bile reflux)

3. Caused by
a. Decreased LES tone (aging)
b. Hiatal hernia: can cause the reflux or can be caused by the reflux
c. Smoking, alcohol, medications that relax the LES (Ca2+ channel blockers, beta blockers, nitrates)
d. Central obesity, pregnancy (from pressure and progesterone)
e. Delayed gastric emptying: due to eating fat-rich, protein-rich meals, especially late at night

4. Symptoms are not closely correlated with the severity of the gross/microscopic findings and include:
a. Heartburn
b. Regurgitation
c. Dysphagia

5. May result in
a. Erosion and ulceration
b. Stenosis
c. Shortening of the esophagus; creating or worsening a hiatal hernia
d. Barrett esophagus and adenocarcinoma

Front 261

GERD histology

Back 261

1. Dilatation of intercellular spaces; loss or defective intercellular junctions

2. Papillary hyperplasia: elongation of lamina propria papillae (papillae extending into the top third of the epithelial layer)

3. Basal zone hyperplasia: basal cell zone exceeding 20% of the epithelial thickness; in response to the acidity

4. Intraepithelial infiltration by inflammatory cells (particularly eosinophils)

Front 262

Barrett esophagus

Back 262

1. Associated with columnar (intestinal) metaplasia of the distal/lower esophagus (normally squamous epithelium)

2. Long-segment Barrett: metaplasia 3cm or more above the gastroesophageal junction

3. Short-segment Barrett: within 3 cm of the gastroesophageal junction

4. Reddish mucosa located between the smooth pearly white esophageal squamous mucosa and the lighter brown gastric mucosa

5. Consequence of long-standing reflux esophagitis
i. The columnal epithelium is more resistant to acid/peptic injury

6. risk of dysplasia and adenocarcinoma

7. single most important risk factor for esophageal adenocarcinoma

Front 263

Infectious Esophagitis

Back 263

1. Occurs mostly in immunocompromised or debilitated individuals; can occur in the immunocompetent

caused by:
1. Candidiasis
2. Herpres
3. cytomegalovirus

Front 264

Candidiasis Infectious Esophagitis

Back 264

a. White-gray patches; yeast forms within

b. Can be anywhere; particularly in mucosal areas (oral and genital)

Front 265

Herpes Infectious Esophagitis

Back 265

a. Small punched out mucosal ulcerations

b. Viral inclusions in squamous epithelial cells at ulcer margins

Front 266

Cytomegalovirus Infectious Esophagitis

Back 266

a. Viral inclusions located in the submucosa, capillary endothelium (unlike the epithelial inclusions of the herpes virus), and in the stromal cells at the base of the ulcers

b. Broad large ulcers; “giant” mucosal ulcerations

Front 267

Benign Neoplasms in the Esophagus

Back 267

1. they are infrequent

2. Leiomyomas are the most common

3. Squamous papillomas (some may be associated with HPV)

Front 268

Carcinomas of the esophagus

Back 268

1. two main types are squamous cell carcinoma and adenocarcinoma

2. Trends
a. Declining incidence in US of squamous cell carcinoma
b. Increasing incidence of adenocarcinomas; especially white males
c. Worldwide, squamous cell cancers constitute 90%
d. In the us, adenocarcinoma represents up to 50% of all cases

3. Most cases of esophageal cancer (regardless of type), are diagnosed after invasion and dissemination
- so poor prognosis

4. Extension into adjacent mediastinal structures occurs early

5. Poor prognosis regardless of type

Front 269

Squamous cell carcinoma
(Of esophagus)

Back 269

1. Male > female

2. Black > white; most common type among blacks

3. More commonly found in the middle third (50%) of the esophagus; while 20% occur in the upper third (perhaps associated with Plummer-Vinson syndrome) and 30% in the lower third

4. Invasive carcinoma follow squamous dysplasia and squamous carcinoma in situ

5. High incidence in eastern and southern Africa, eastern and central Asia

Hint 269

squamous cells are squished in the middle of the esophagus

Webs are flat...like squamous cells

Front 270

Risk factors of Esophageal squamous cell carcinoma

Back 270

i. Smoking and alcohol (strong independent and synergistic effect)
ii. Vitamin deficiency: Vit A, C, riboflavin, thiamine, pyridoxine
iii. Other micronutrient deficiency: zinc, molybdenum
iv. Chronic esophagitis
v. Achalasia
vi. Plummer-Vinson syndrome
vii. Mold contaminated grains (Fusarium moniliforme)
viii. Nitrosamines
ix. Human papilloma virus
x. Drinking “yerba mate” (a hot beverage in South America)
xi. Betel nut chewing (India and other places in Asia)

Front 271

Esophageal Adenocarcinoma

Back 271

a. Men > female

b. White > black; most common type in US among whites, particularly white males

c. Most occur in the lower third of the esophagus

d. Invasive carcinoma follows Barrett esophagus (intestinal metaplasia) and dysplasia

e. Risk factors
i. Those associated with reflux esophagitis and Barrett esophagus --> so anything that's going to decrease LES tone and cause increased abdominal pressure

Hint 271

mostly occurs in the lower esophagus because it's associated with reflux esophagitis

Front 272

Stomach Congenital Anomalies

Back 272

1. heterotopias

2. pyloric stenosis

Front 273

Heterotopias

Back 273

1. misplaced tissue

2. synonymous with ectopic

Front 274

Heterotopias - types

Back 274

1. pancreatic heterotopia

2. gastric heteroptopia

Front 275

pancreatic heterotopia

Back 275

1. ectopic pancreatic nodules in the wall of the stomach or intestine

2. usually in the submucosa, but can penetrate through the wall

3. contents of the pancreatic tissue drain into the stomach

Front 276

Gastric hetertopia

Back 276

1. patches of ectopic gastric mucosa

2. locations
i. Proximal/upper esophagus (inlet patch)
• Patch of reddish mucosa (should be pearly white)
ii. Duodenum
• Can be ectopic but more commonly heteroplastic because of the acidity (acid gets into the duodenum and stimulates the cells to shift from intestinal to gastric)
• Associated with peptic ulcers in duodenum
iii. Meckel diverticulum
• Located in the distal ileum
• Diverticulum can also have gastric mucosa inside

Front 277

Congenital Pyloric Stenosis

Back 277

1. Results from hypertrophy and hyperplasia of the muscularis propria of the pylorus

2. Occurs in newborns and manifests in the 2nd or 3rd week of life

3. boys > girls (3-4:1)

4. Familial occurrence; high rate of concordance in monozygotic twins

5. Results in:
a. Regurgitation
b. Nonbilious (not green), projectile vomiting

6. Physical signs
a. Visible peristalsis
b. Firm, ovoid palpable mass in region of the pylorus; feel olive mass in pylorus

7. Treatment of surgical muscle splitting (pyloroplasty); curative

Front 278

Pyloric Stenosis in the Adult

Back 278

1. acquired and rare

2. Idiopathic and hypertrophic

3. Gastric outlet obstruction caused by:
a. Chronic gastritis
b. Peptic ulcers
c. Cancer

Front 279

Gastritis
(definition)

Back 279

inflammation of the gastric mucosa

Front 280

Acute gastritis

Back 280

1. Acute in onset but can last a long time; associated with acute “stress” ulcers

2. Transient or dominated by congestion, edema, PMN infiltrate (mostly neutrophils)

3. Manifestations are variable and may be asymptomatic

4. One of the major causes of massive hematemesis and melena

5. May cause mucosal erosions and ulcerations

6. Bleeding can be massive and can be fatal

Front 281

Acute Gastritis
(Etiology)

Back 281

1. Drug-induced: Prostaglandin inhibitors (aspirin and NSAIDS); steroids; cancer chemotherapy

2. Ethanol-induced

3. Stress gastritis: trauma, burns, surgery (medicate prophylactically to prevent stress ulcers)

4. Ischemic gastritis: shock

5. Acute corrosive gastritis: ingestion of acids and alkali; accidental, suicide attempts

6. Bile reflux gastritis: distal gastrectomy with gastroenteroanastomosis

7. Uremia: uremic gastropathy

8. Hyperparathyroidism: hypercalcemia stimulates hypergastrinemia and acid secretion

Front 282

Erosions

Back 282

defect does not go beyond the muscularis mucosae; superficial; small, < 5 mm

Front 283

Ulcers

Back 283

defect that goes beyond the muscularis mucosae; > 5 mm

Front 284

Acute “stress” ulcers

Back 284

1. manifestations of acute gastritis

2. Occur in patients in shock, with extensive burns, sepsis, or severe trauma, any condition that raises intracranial pressure (trauma, brain surgery, etc.)

3. Types
i. Curling ulcers: associated with severe burns or trauma
ii. Cushing ulcers: associated with intracranial injury, operations, or tumors

4. Morpholgy
i. Small; less then 1 cm
ii. Often multiple; no specific location throughout the stomach and duodenum
iii. Gastric rugal pattern is essentially normal
iv. Margins and base of the ulcer are not indurated; punched-out appearance
v. Heal with complete re-epithelialization

Front 285

Chronic Gastritis

Back 285

1. presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and intestinal metaplasia, usually in the absence of erosions

2. Chronic “peptic” ulcers

3. Long-lasting and dominated by lymphocytes and plasma cells
a. Variable participation of acute inflammatory cells (neutrophils)
b. Presence of neutrophils within the glandular and surface epithelial layer signifies “active” inflammation (chronic “active” gastritis)

Front 286

Chronic Gastritis
(Subtypes)

Back 286

Non-atrophic

atrophic - environmental

atrophic - autoimmune

Front 287

Non-atrophic Gastritis

Back 287

i. Associated with
• Helicobacter pylori infection
• Hyperacidity (hyperchlorhydria)
• May develop distal ulcers in the pyloric channel and the first part of the duodenum

ii. NOT associated with developing an intestinal metaplasia, dysplasia or gastric cancer (may be protective for unknown reasons)

iii. Dominant type except in minority populations

iv. Treatment with antacids and proton pump inhibitors because H. pylori loves acid

Front 288

toluidine blue

Back 288

a special stain for H. pylori

Front 289

atrophic - evironmental gastritis

Back 289

i. Atrophy (loss of glands)

ii. Associated with
• Helicobacter pylori infection
• Minority populations; especially Asian
• Hypochlorhydria (low acidity)
• Gastric ulcers (proximal to the pyloric channel)
• Intestinal metaplasia, dysplasia and adenocarcinoma

iii. Usually found proximal to the pyloric channel

iv. Associated with gastric cancer (adenocarcinoma) where there is an increase in goblet cells [LYN]

v. Ulcers are related to the atrophy, not the increased acidity; proton pump inhibitors will not help these ulcers

Front 290

Autoimmune gastritis

Back 290

1. also known as “type A” gastritis

i. Atrophy of oxyntic (acid-producing) mucosa; form of atrophic gastritis

ii. Autoantibodies to parietal cells including antibodies against:
• Intrinsic factor
• H+-K+ ATPase
• Gastrin receptor

iii. Familiar occurrence (suggested autosomal dominant inheritance); especially Northern European descent

iv. Associated with
• Loss of intrinsic factor causes vitamin B12 deficiency and pernicious anemia (megaloblastic anemia)
• Severe hypochlorhydria that induces marked hypergastrinemia (low acidity signals cells to release gastrin); hypergastrinemia induces neuroendocrine cell hyperplasia and carcinoid tumors
• Intestinal metaplasia, dysplasia, and adenocarcinoma
• Other autoimmune disorders: Hashimoto thyroiditis, Addison disease, type I diabetes

v. Increased risk of gastric cancer, possibly due to chronic inflammation and intestinal metaplasia

Front 291

Peptic ulcer disease

Back 291

a. Chronic ulcers that are manifestations of chronic gastritis

b. Morphology
i. Small with nice margins; confluent with the surrounding tissue
ii. Most are less then 4 cm in diameter
iii. Sharp, punched out walls
iv. Not raised or indurated signifies most likely a benign lesion
v. Smooth, clean base (due to peptic digestion)
vi. Patent or thrombosed blood vessels may be evident
vii. Scaring causes puckering or radiation of mucosal folds from the ulcer crater

Front 292

Peptic ucler disease
(Subtypes)

Back 292

1. separated by location

i. First portion of the duodenum (usually the anterior wall) and pyloric channel ulcers

ii. Stomach proximal to the pyloric channel (usually on the lesser curvature, at incisura angularis)

iii. Multiple sites simultaneously involved (stomach, duodenum, jejunum)

Front 293

Peptic ulcer - First portion of the duodenum (usually the anterior wall) and pyloric channel ulcers

Back 293

• Associated with:
1. Non-atrophic gastritis

2. Hyperacidity (hyperchlorhydria)

3. Helicobacter pylori infection

Front 294

Peptic ulcer - Stomach proximal to the pyloric channel

Back 294

• Associated with:
1. Helicobacter pylori infection
2. Atrophic gastritis
3. Hypochlorhydria

Front 295

Peptic ulcer disease - Multiple sites simultaneously involved

Back 295

• Associated with:
1. Zollinger-Ellison syndrome: gastroma overproduces gastrin (hypergastrinema) which increases acid production; the increased acid results in multiple ulcers everywhere

Front 296

Histological Zones of Peptic ulcer disease

Back 296

i. Superficial layer of necrotic debris

ii. Fibrinopurulent exudates: inflammatory exudates, neutrophils

iii. Granulation tissue

iv. Fibrous or collagenous scar, thickened vessels occasionally thrombosed (deepest layer)

Front 297

Complications of Peptic ulcer disese

Back 297

i. Bleeding

ii. Perforation

iii. Obstruction from edema and scarring

iv. Tendency to recur, particularly if H. pylori is not eradicated

Front 298

Helicobacter pylori

Back 298

A. Bacteria that is very well adapted to the gastric microenvironment

B. Adaptations:
1. Produce urease: brakes endogenous urea into ammonia which buffers the gastric acidity
2. Flagella: allow motility through the viscous mucous
3. Adhesins such as BabA: allows binding to epithelial cells; does not invade the epithelial cells
4. Cytotoxins such as CagA and VacA: injure the epithelium as a source of nutrients; the organism does not invade the mucosa

C. Mostly acquired in childhood through fecal-oral and oral-oral routes

D. High prevalence of infection which increases with age
1. ~ 50% adults over age 50 are seropositive
2. Even higher among minority populations

E. Not clear why the same organism causes non-atrophic gastritis (no risk for cancer) in some individuals while in others it causes atrophic gastritis (risk for cancer)

F. Responsible for most peptic ulcers (gastric and duodenal)

G. Contributes to the pathogenesis of gastric carcinomas and lymphomas

H. Diagnosis based on:
1. Gastric biopsies
a. Rapid urease test: used in the enodoscopy suite to test a piece of mucosa for the presence of H. pylori
b. Special stains: Steiner, Giesma, Toluidine blue, Alcian yellow
2. Urea breath test: can also give a patient urea and if urease is present the metabolites can be detected in the breath
3. Measuring antibodies against the organism (serology)
4. Detection in feces (PCR)

Front 299

Bezoars

Back 299

A. Luminal concretions of indigestible ingested material (foreign bodies trapped in the stomach)
1. Phytobezoars: derived from plant/vegetable material
2. Trichobezoars: hairballs

B. Occur in
1. Dysmotility (gastroparesis): alteration of normal stomach movement after a partial gastrectomy or in diabetes
2. Partial gastric outlet obstruction
3. Children or patients with neuropsychiatric disorders: eat anything and everything including objects that can’t pass through the duodenum

Front 300

Benign Gastric Tumors

Back 300

Polyps - any nodule or mass that projects above the level of the surrounding mucosa and into the lumen

Front 301

Gastric polyps

Back 301

a. Hyperplastic polyps: non neoplastic

b. Adenomatous polyps: neoplastic

Front 302

Hyperplastic polyps

Back 302

i. >90% of gastric polyps

ii. No malignant potential

iii. Hyperplastic surface epithelium

iv. Non-neoplastic

Front 303

Adenomatous polyps

Back 303

i. Dysplastic epithelium

ii. Similar to colonic adenomatous polyps

iii. Malignant potential

iv. neoplastic

Front 304

Malignant gastric tumors

Back 304

1. adenocarcinoma

2. Lymphomas

3. Carcinoid tumors

4. Gastrointestinal stromal tumors (GIST):

Front 305

Gastric Adenocarcinoma

Back 305

1. 90-95% of all tumors

2. Decreased incidence and mortality rate in the USb.

3. Still the 2nd most common cause of cancer death worldwide

4. More common in lower socioeconomic groups and racial minorities, particularly blacks, Asians, and Hispanics

5. Successive migrant generations acquire the level of risk that prevails in the new locales

Front 306

Gastric Adenocarcinoma
(subtypes)

Back 306

1. Intestinal (expanding) type

2. Diffuse (infiltrative) type

Front 307

Intestinal (Expanding) type Adenocarcinoma

Back 307

1. Very similar to ones seen in colon

2 Forms tumoral glands

3 Grow with a cohesive expanding pattern

4. Mean age 55

5. Male to female ratio 2:1

6. Decreasing in incidence worldwide

7. Related to chronic gastritis and H. pylori infection

8. Related to environmental factors and shows geographic variation in incidence

9. Preceded by intestinal metaplasia-dysplasia sequence

Front 308

Important environmental factors

Back 308

1. Infection by H. pylori

2. Lack of refrigeration/electricity; consumption of preserved, smoked, cured, pickled and salted foods

3. Lack of fresh fruit and vegetables that contain antioxidants such as ascorbate (vitamin C), alpha-tocopherol (vitamin E), and beta-carotene

4. Water contamination with nitrates that generate carcinogenic nitrosamines (common in Andes mountains)

5. Common throughout the Andes and volcanic areas (Chile, Columbia, Nicaragua), Costa Rica, Japan, Korea; in the US it is found particularly in California and areas of the southwest

Front 309

Diffuse (infiltrative) type of Gastric Adenocarcinoma

Back 309

1. Does not form glands

2. Infiltrative growth pattern of scattered individual cells or small groups of cells

3. Some of the cells may have loss of cytoplasm

4. Signet ring conformation may occur (signet ring cell carcinoma) due to the accumulation of mucin inside the cells

5. Seen in the younger population, mean age 48

6. Equal male to female ratio

7. No change in incidence

8. Not related to environmental factors and there is very little geographic variation in incidence

9. Not related to chronic gastritis or H. pylori infection

10. No clear premalignant conditions

Front 310

Other risk factors for Gastric Adenocarcinoma

Back 310

1. Partial gastrectomy: favors reflux of bilious fluid

2. Blood group A individuals have a slightly increased risk

3. Family history of gastric cancer

4. Hereditary nonpolyposis colon cancer syndrome

5. Autoimmune gastritis

6. E-cadherin gene mutations: associated with diffuse gastric carcinomas and lobular breast carcinomas

Front 311

Gross morphology of Gastric Adenocarcinoma

Back 311

i. Most located on the lesser curvature at the level of the incisura angularis of the stomach

ii. An ulcer outside of the lesser curvature (on the greater curvature) is more likely to be malignant than benign because benign tumors tend to occur at the lesser curvature as well; in other words, benign and malignant are both more commonly found on the lesser curvature but a lesion found outside the lesser curvature is most likely malignant

iii. Malignancy ulcers have (compared to peptic ulcers):
• Heaped-up, beaded, indurated margins
• Shaggy, necrotic bases
• Larger in size (>4 cm)

iv. Growth patterns can be exophytic (grows outward), flat/depressed, or excavated/ulcerated

Front 312

Linitis plastica

Back 312

1. Diffuse type of gastric carcinoma may induce dense fibrosis (described as scirrhous or desmoplastic) and may infiltrate a broad region of the gastric wall or the entire stomach creating a ridge

2. Extensive thickening of the wall of the stomach

3. Leather bottle-like stomach

Front 313

Early gastric carcinoma

Back 313

1. Lesion confined to the mucosa and submucosa

2. Good prognosis regardless of the presence or absence of lymph node metastases

3. Very high survival rate

Front 314

Advanced gastric carcinoma

Back 314

1. Lesion extends beyond the submucosa and penetrates the muscularis mucosa

2. Very poor prognosis and very poor survival

Front 315

Virchow’s node:

Back 315

1. gastric carcinomas may metastasize to a left supraclavicular lymph node as the first clinical manifestation

2 Solitary, palpable, superclavicular lymphadenopathy, especially on the left side

3. Sentinel lymph node is indurated and is often associated with lung caner (can be on either side)

4. A sign of presumptive occult visceral malignancy; historically indicative of gastric adenocarcinoma

Front 316

Sister (Mary) Joseph’s node

Back 316

1. gastric carcinomas may metastasize to the periumbilical region

2. Not really a lymph node but a soft tissue metastasis

3. Historically associated with mostly gastric cancer but now more likely associated with ovarian carcinomas in females

4. Named after a nun/nurse who noted this lesion as a marker of metastatic caner

Front 317

Krukenberg tumor

Back 317

gastric signet-ring cell type carcinoma metastatic to the ovary, usually bilateral

Front 318

Lymphomas

Back 318

a. Low and high grade lymphomas of mucosa-associated lymphoid tissue (MALTOMAS)

b. Related to H. pylori infection

c. Low grade lymphomas may regress after successful eradication of the infection

Front 319

Carcinoid tumors

Back 319

1. gastric neuroendocrine cell tumors

2. Rare, tend to be infiltrative

3. Metastasize in about 33% of cases

Front 320

Gastrointestinal stromal tumors (GIST)

Back 320

1. stromal tumors originating in the stomach and intestine with variable malignant potential

2. Originate in interstitial cells of Cajal (the GI pacemaker cells)

3. look like spindle-cell neoplasms and resemble benign sarcomas

4. 95% express C-kit (CD 117), a membrane tyrosine kinase (transduction protein)

5. Location
i. Stomach 50-70%
ii. Small intestine 33%
iii. Colon 5-15%

6. Poor prognosis if the lesion is large, has high mitotic activity, and if tumor necrosis is present

7. Unresectable tumors are now treated with Gleevac, a drug that inhibits C-kit (also used to treat myelogenous leukemia)

Front 321

Congenital anomalies of the intestine

Back 321

1. Atresia

2. Anorectal anomalies

3. Duplication

4. Malrotation

5. Omphalocele, Gastroschisis

6. Meckel Diverticulum

7. Hirschprung Diseases

Front 322

Intestinal Atresia and Stenosis

Back 322

1. More common in the duodenum than elsewhere in intestine

2. Atresia occurs as an imperforate mucosal diaphragm, string-like segment, or interruption
a. Types: diaphragm, cord, gap, apple peel, multiple gaps

3. Due to developmental failure or ischemia

Front 323

Anorectal anomalies

Back 323

(imperforate anus)

1. Etiology:
a. Failure of the anal membrane to involute
b. Failure of the urorectal septum to split the cloacal cavity (distal hindgut)
c. Failure of the hindgut (intestine portion supplied by the inferior mesenteric artery) to descend

2. Incidence: 1 in 5000; high frequency (50-60%) of association with other congenital abnormalities

3. Classified in relation to the puborectalis m.:

Front 324

low imperforate anus

Back 324

1. below the puborectalis

2. Anal stenosis

3. Anal atresia
• Thin membrane residing within normal anal sphinter
• Resolved by puncturing the membrane

4. Anal agenesis with an externally visible fistula (perineal, vestibular)
• LYN: Girls: anovestibular, anocutaneous fistula (latter is an ectopic anus)
• Boys: anocutaneous fistula

Front 325

intermediate imperforate anus

Back 325

1. at the level of the puborectalis

2. Rectal atresia (isolated with normal anus)

3. Anorectal agenesis with an externally visible or hidden fistula (genitourinary [GU])
• LYN: Girls: rectovestibular, rectovaginal fistula
• Boys: rectourethral fistula (bulbar urethra)

Front 326

high imperforate anus

Back 326

1. above the puborectalis

2. Anorectal agenesis with hidden fistula (internal; goes into vagina in girls, prostatic urethra in boys)

*. So, agenesis occurs in all locations and may or may not show a fistula.

Front 327

Intestinal Duplication

Back 327

1. Error in enteric canalization, forming:
a. Enterogenous cysts (closed duplication with cystic structure paralleling true intestinal lumen) in 75% of cases
b. Short or long tubular duplications that may communicate with the main lumen
• Giant diverticulum if open (communicating) at one end
• Ileum duplex if open at both ends

2. Most common in jejunum and ileum
a. Most common in the distal small intestine

3. Presents with obstruction, mass, or bleeding

Front 328

Intestinal Malrotation

Back 328

1. Nonrotation or incomplete embryologic rotation of the gut, resulting in lack of proper fixation of the cecum to the right lower quadrant

2. the cecum needs to rotate to its normal position in the lower right quadrant

3. Predisposes patient to obstruction by:
a. Volvulus (twisting of the intestine) causing strangulation of the SMA and necrosis
b. Ladd bands (fibrous bands between the cecum and right side of the abdominal wall that compress the duodenum when the cecum has not crossed the duodenum)
i. Fibrous bands cross over the duodenum and cause obstruction

Front 329

Nonrotation

Back 329

cecum remains in left upper quadrant, leaving the small intestine on right side

Front 330

Incomplete rotation

Back 330

cecum stops in right upper quadrant (subhepatic) after crossing duodenum anteriorly or posteriorly

Front 331

Defects in the abdominal wall

Back 331

1. omphalocele

2. gastroschischis

* both are herniations

Front 332

Omphalocele

Back 332

1. Abdominal wall defect allowing herniation
of viscera into the base of the umbilical cord

2. Prolapsed organs covered by outer layer of amnion
and inner layer of peritoneum

3. Frequently (>50%) associated with
other serious congenital defects

Front 333

Gastroschisis

Back 333

1. Abdominal wall defect adjacent but not involving
the umbilicus (almost always to right)

2. Prolapsed organs not covered
by membranes, amnion, nor peritoneum

3. Infrequently associated with
other congenital anomalies

Front 334

Meckel diverticulum

Back 334

1. True (congenital) diverticulum in the small intestine consisting of all layers of the intestine(mucosa, submucosa, and muscularis propria)

2. Due to incomplete involution of the vitelline duct (aka omphalomesenteric duct), which connects the intestinal lumen with the yolk sac

3. Heterotopic gastric mucosa or pancreatic tissue present in 50% of cases may cause peptic ulceration and massive GI bleeding

4. Antimesenteric location within 2 feet of the ileocecal valve

5. Predisposes patient to volvulus

6. Most are asymptomatic (not detected until adult goes in for abdominal surgery for other reason)

7.2 inches long, 2 feet from the end of the ileum, 2% incidence in population, 2 types of tissue may be present

Front 335

Hirschsprung disease

Back 335

1. congenital aganglionic megacolon; a neurocrestopathy

2. Congenital aganglionosis (absence of ganglion cells) in Meissner (submucosal) and Auerbach (myenteric) plexuses

3. Caused by an arrest in the migration of neural crest cells, which normally migrate from proximal to distal

4. Aganglionic section does not have normal peristalsis

5. Defect begins in anus and moves proximally, so that most cases of Hirschsprung disease only involve the rectum and sigmoid colon

Front 336

short-segment aganglionosis

Back 336

due to a late migration stop

more common in boys

classic Hirschprung

Front 337

long-segment aganglionosis

Back 337

1. migration stopped early)

2. affects a longer segment (often the entire colon) and

3. is traditionally considered more common in girls

Front 338

aganglionosis controversy

Back 338

1. long-segment form seems to be more common in boys, but total colonic aganglionosis is more common in girls.

2. As the aganglionosis moves proximal, the frequency of girls affected increases.

3. May involve entire intestine, but small bowel involvement is rare

Front 339

Hirschprung disease - Symptoms

Back 339

1. Failure to pass meconium

2. Obstipation (severe constipation)

3. Massive distention of the colon (megacolon) proximal to the aganglionic segment**
i. The dilated portion has ganglia; the non-dilated portion lacks ganglia.**

4. Superimposed enterocolitis

5. Perforation, most often at the cecum

Front 340

Hirschprung disease
(demographics)

Back 340

1. Most cases are sporadic, but familial forms do exist.

2. Association with Down Syndrome (10% of cases)

3. Familial forms have been traced to defects in genes regulating neurogenesis, in particular the RET oncogene and its ligands.** (7 other genes have been implicated)

5. Male:female ratio is 4:1

Front 341

Dysentery

Back 341

diarrhea with blood and mucus; associated with pain, tenesmus, and fever

Front 342

Steatorrhea

Back 342

bulky/greasy/pale stools with excess fat (malabsorption diarrhea with impaired absorption of fat and fat-soluble vitamins

Front 343

Gastroenterities, enterocolitis

Back 343

A. Nonspecific terms implying inflammation of the gastrointestinal tract

B. Major manifestation: diarrhea

Front 344

Diarrhea

Back 344

1. an “increase in stool mass volume,

2. decrease in stool consistency,

3. increase in frequency of bowel movements

Front 345

Diarrhea Classifications

Back 345

1. Exudative

2. Secretory

3. Osmotic

4. Malabsorption

5. It is common to see mixed mechanisms

Front 346

Exudative Diarrhea

Back 346

1. Inflammatory (>10 WBC per 10 high power fields microscopically, typically many PMNs)

2. Dysentery-like (diarrhea with blood and mucus, associated with pain and fever)**

Front 347

Secretory diarrhea

Back 347

isotonic, watery, voluminous (>500mL), noninflammatory, persists with fasting

Front 348

Osmotic diarrhea

Back 348

1. voluminous, hyperosmolar (ingestion of nonabsorbable solutes, i.e. cathartics and laxatives),

2. abates with fasting

3. Caused by antacids, sugar substitutes, fat substitutes

Front 349

Malabsorption diarrhea

Back 349

1. defective absorption of ingested food items;

2. also qualifies as osmotic (nutrients remaining in the intestine draw water into the lumen)

Front 350

Diarrhea classifications based on infections v. non-infections processes

Back 350

1. Infectious mostly secretory-type diarrhea

2. Infectious mostly exudative-type diarrhea

3. Non-infectious mostly secretory-type diarrhea

4. Non-infectious mostly exudative-type diarrhea

5. Non-infectious mostly osmotic-type diarrhea

6. Non-infectious mostly malabsorptive-type diarrhea

Front 351

Infectious mostly secretory-type diarrhea

Back 351

1. watery, isotonic, and voluminous

2. Do not expect to see fever

3. Mostly small bowel conditions (80% of fluid absorption normally occurs in the small intestine)

4. Viral:
• Rotavirus (the most common in infants)
• Norwalk virus (older children, adults)

5. Toxigenic bacteria: produce cytotoxins that cause the diarrhea (not invading)
• E. coli, enterotoxigenic (most common cause of traveler’s diarrhea)
• Vibrio cholerae (causes very voluminous, isotonic diarrhea; “rice water”)

6. Parasites:
• Giardia (also causes malabsorption; discussed below)
• Cryptosporidium (discussed below)

Front 352

Infectious mostly exudative-type diarrhea

Back 352

1. Mostly large bowel involvement, dysentery-like, leukocytes and blood in stool

2. Invasive bacteria: destroying the mucosa so that bloody stools
• Campylobacter (most common in U.S.)
• E. Coli, enteroinvasive
• Shigella
• Salmonella
• Yersinia

4. Toxigenic bacteria:
• Clostridium difficile
• E. coli, enterohemorrhagic
• Shigella

5. Invasive parasites: Entamoeba organisms (discussed below)

Front 353

Non-infectious mostly secretory-type diarrhea

Back 353

1. Most common cause: neoplasms (mostly neuroendocrine tumors [pancreatic or carcinoid] that elaborate hormonal peptides that cause diarrhea)

2. Polyposis with lymphatic obstructin (protein-losing enteropathy)

3. Microscopic colitis, collagenous colitis (discussed below)

Front 354

Non-infectious mostly exudative-type diarrhea

Back 354

Ulcerative colitis (

Front 355

Non-infectious mostly osmotic-type diarrhea

Back 355

1. Laxatives

2. Antacids (MgSO4 and other magnesium salts)

3. Sugar and fat substitutes (dietetic food, chewing gum, sorbitol, mannitol, olestra)

Front 356

Non-infectious mostly malabsorptive-type diarrhea

Back 356

1. Disaccharidase (lactase) deficiency

2. Abetalipoproteinemia

3. Steatorrhea
i. Pancreatic insufficiency with lack of pancreatic digestive enzymes
ii. Bliary obstruction with lack of bile salts required for fat emulsification and absorption

4. Sprue

5. Crohn disease

6. Short bowel syndrome (any process that shortens the small intestine, particularly ileal resection)

Front 357

Salmonella enteritidis

Back 357

1. major source is Animal feces-contaminated poultry

2. causes dysentery

Front 358

S. typhimurium

Back 358

1. major source is Animal feces-contaminated poultry

2. causes dysentery

Front 359

Salmonella typhi

Back 359

1. found in humans with no animal reservoir

2. Causes :
i. Disseminated typhoid fever
ii. Chronic gallbladder infections
iii. Asymptomatic carrier state (“Typhoid Mary”)

Front 360

Enterohemorrhagic E. coli

Back 360

1. verocytotoxin-producing E. coli

2. particularly type O157:H7

3. May cause hemolytic uremic syndrome (HUS),

Front 361

hemolytic uremic syndrome (HUS)

Back 361

1. endothelial injury characterized by

2. Microangiopathic hemolytic anemia

3. Renal failure

4. Thrombocytopenia (abnormally small number of circulating platelets in blood because platelets trapped in capillaries)

Front 362

Shigella, Salmonella, Campylobacter, Yersinia

Back 362

1. may also cause HUS

2. Shiga-like toxins precipitate the syndrome by endothelial damage.

Front 363

Reiter syndrome

Back 363

1. reactive arthritis, urethritis, and conjunctivitis

2. particularly in susceptible individuals (HLA-B27 genotype

3. caused by Shigella, Salmonella, Campylobacter, Yersinia

Front 364

Giardia lamblia

Back 364

1. localizes mostly in the duodenum

2. Diagnosed by duodenal biopsy, duodenal aspirate, finding cysts in stool

3. May cause blunting of the villi and malabsorption with diarrhea lasting for months to years
a. Diarrhea may be secretory or malabsorptive.

4. Resistant to chlorination of water but not to sand filtration

5. Secretory IgA is important to control the infection (agammaglobulinemic individuals are severly affected)

Front 365

Cryptosporidiosis

Back 365

1. mostly affects the small intestine, causing chronic secretory diarrhea**

2. Mostly seen in immunosuppressed individuals

3. Outbreaks associated with poorly cooked hamburgers

Front 366

Entamoeba histolytica

Back 366

1. populates the colon, causing exudative diarrhea**

2. Causes colitis, flask-shaped ulcers (narrow opening, wide base), and dysentery.
a. Diagnose by identifying trophozoites

3. Amoeba may invade the intestine, migrate to the liver, and cause liver abscesses (lungs may be next migration site).

Front 367

types of non-infectious enterocolitis

Back 367

1. Necrotizing enterocrolitis (NE)

2. Pseudomembranous (antibiotic-associated) colitis

3. Microscopic colitis

4. Inflammatory bowel disease (IBD)

Front 368

Necrotizing enterocrolitis (NE)

Back 368

1. Acute, necrotizing inflammation predominantly affecting the terminal ileum and ascending (proximal) colon
a. Full thickness of the intestinal wall undergoes gangrenous necrosis

2. Primarily affects neonates (especially preemies and low birth weight babies)
a. NE is the most common GI emergency in neonates

3. Peak incidence on initiation of oral feeding

4. Etiology: unknown but postulated
a. Abnormal response to gut colonization with bacteria and exposure to toxins on onset of oral feeding
b. Immature gut immune system
c. Deranged intestinal blood flow causing ischemia

5. May require extensive resections, so that the babies may develop short intestine syndrome with malabsorption due to decreased surface area.

Front 369

Pseudomembranous (antibiotic-associated) colitis

Back 369

1. Disruption of the normal flora by broad-spectrum antibiotics allows resistant toxin-forming bacterial strains to flourish and cause diarrhea
a. Inflammation in glands and crypts erupt, forming a mushrooming fibrinopurulent exudates that adheres to the damaged surface
i. Gross appearance: visible, yellowish plaque overlying colonic mucosa
b. Most implicated bacteria: C. difficile
c. Most implicated antibiotic: clindamycin
i. Really, any antibiotic can be associated
ii. Rarely occurs in the absence of antibiotic therapy

2. Diagnosis by detection of increased levels of C. difficile exotoxins (A and B) in stool

3. Endoscopy shows pseudomembrane that is fibrinopurulent exudate adherent to the mucosa

4. Treatment: vancomycin

Front 370

C. difficile

Back 370

i. Produces exotoxins A and B, which damage the intestinal mucosa

ii. Rarely are other microorganisms implicated

Front 371

Microscopic colitis

Back 371

1. Chronic (weeks to months), secretory-type diarrhea of unknown etiology

2. Normal gross (endoscopic) appearance

3. Positive microscopic findings:
a. Band-like collagen deposition under the epithelial surface (“collagenous colitis”)
i. Diagnosed when collagen is 5+ microns thick
ii. This form is 10x more common in women (particularly older women) than men.
b. Prominent intraepithelial infiltrate of lymphocytes (“lymphocytic colitis”)
i. Associations: sprue (discussed below), autoimmune diseases (autoimmune gastritis, thyroiditis)
ii. This form affects men and women equally.

Front 372

Inflammatory bowel disease

Back 372

1. Chronic, idiopathic, inflammatory condition causing intermittent exudative-type diarrhea attacks

2. Two entities
a. Crohn’s disease (CD, aka regional enteritis)
b. Ulcerative colitis

Front 373

Inflammatory bowel disease

(Postulated Mechanisms)

Back 373

1. Exaggerated immune response to normal flora

2. Defects in the epithelial barrier function

3. Genetic predisposition
i. HLA-DR1/DQw5 allelic combination (seen in 27% of North American white patients with the disease)
ii. HLA-DR2 increased in patients with ulcerative colitis
iii. HLA-B27 occurs in high frequency in patients with IBD and ankylosing spondylitis

4. Failure to down-regulate mucosal immune response (shows clinical improvement following immunosuppressive therapy)

5. Questionable autoimmune mechanisms

Front 374

Crohn’s disease (CD, aka regional enteritis)

Back 374

i. Sharply delineated involved segments with intervening unaffected (skip) areas
• Terminal ileum is most commonly affected site
• Small intestine alone affected in 40% of cases
• Small intestine and colon (30%)
• Colon alone (30%)
• May also involve the mouth, esophagus, stomach, duodenum, and anus

ii. Anti-saccharomyces cerevesiae antibody (ASCA**) more commonly seen in CD than ulcerative colitis (UC)
• Marker

Front 375

Crohn’s disease
(microscopically)

Back 375

1. Transmural inflammation
i. See (lymphoid aggregates (from mucosa through serosa) at all levels of the bowel wall)**

2. Noncaseating granulomas (characteristic but not pathognomonic; in 50% of cases)**

3. Cryptitis (accumulation of acute exudates in crypts) and crypt abscesses (accumulation of neutrophils in crypt lumen) (less often than with UC)

4. Characteristic linear ulcers that are narrow, slit-like, and deeply penetrating
i. Like knife cuts
ii. Can generate fistulous tracts

5. Predisposition to cancer (dysplasia-carcinoma sequence) but less often than with UC

Front 376

Crohn’s disease
(grossly)

Back 376

1. Long, linear ulcers and deeply-penetrating narrow fissures
i. Sometimes creating fistulous tracts into other loops of bowel, the urinary bladder, vagina, perianal skin, localized abscesses

2. Segments of rubbery and thick (garden hose) intestinal wall with narrowed lumens
i. So thick that it is difficult to open

3. Creeping fat: mesenteric fat wraps around involved segments; due to transmural inflammation

4. Sharply demarcated skip lesions between involved segments

5. LYN Aphthous ulcers (small mucosal ulcers resembling canker sores), cobblestone mucosa

Front 377

Crohn’s disease
(Demographics)

Back 377

1. Seen most frequently in western populations, whites, Jewish ancestries

2. Females slightly more often affected than males

3. Incidence increasing

4. Peak detection in teens and twenties (minor peak in 50 and 60 year olds)

5. Smoking is a strong exogenous risk factor and worsens the condition

Front 378

Crohn's disease
(assocaited conditions)

Back 378

1. Malabsorption of vitamin B12 causing pernicious anemia

2. Malabsorption of bile salts causing steatorrhea

3. Migratory polyarthritis (MP), sacroilitis (SI), ankylosing spondylitis (AS)

4. Erythema nodosum—inflammation of fat cells under the skin causing tender, red nodules, usually seen on both shins

5. Uveitis—inflammation of the iris and choroid

6. Primary sclerosing cholangitis (very strongly associated with IBD; UC more strongly than CD)

7. Gastrointestinal cancer 5- to 6-fold increased risk compared to age-matched populations (lower than with UC)

Front 379

Migratory polyarthritis

Back 379

temporary migrating inflammation of the large joints, usually starting in the legs and moving upwards

Front 380

sacroilitis

Back 380

inflammation of the sacroiliac joint

Front 381

ankylosing spondylitis

Back 381

arthritis of the spine

Front 382

Ulcerative colitis

Back 382

1. Limited to the colon

2. Begins at the rectum and extends in a continuous fashion proximally
• Rectum always involved
• No skip lesions
• Severe case shows pancolitis with slight back-wash inflammation of terminal ileum

3. Perinuclear anti-neutrophil cytoplasmic antibody (pANCA) more common in UC than CD**

Front 383

Ulcerative colitis
(Microscopic)

Back 383

1. Affects the superficial intestine
i. Predominantly the mucosa, possibly also the submucosa**
ii. LYN diagnostic criteria: cannot be transmural

3. Granulomas are rare (suspect CD when present)

4. Very common but nonspecific crypt abscesses with cryptitis**

5. Extensive ulceration (ulcers are wide and shallow in comparison to CD)

6. Dysplasia-carcinoma sequence (much more than with CD)
i. Characteristic architectural disarray: glands are disorderly.

Front 384

Ulcerative colitis
(Grossly)

Back 384

1. No skip lesions

2. Wall is not thickened

3. Serosa is uninvolved and normal (no creeping fat nor fistulous tracts)

4. Involvement begins and is more severe in the rectum, extending proximally for a variable distance

5. Broad-based ulcerations of the mucosa

6. Islands of regenerating mucosa between the ulcers bulge upward to create pseudopolyps
i. Reactive process
ii. Abundant hyperplasia

7. In the most severe cases, the colon swells and becomes gangrenous (toxic megacolon); it can perforate.

Front 385

Ulcerative colitis
(Demographics)

Back 385

1. More common in whites than blacks

2. Women more often affected the men

3. Onset peaks between 20 and 25 years

4. Smoking may improve the outcome

Front 386

Ulcerative colitis
(Associated Conditions)

Back 386

1. Migrating polyarthritis, sacroilitis, ankylosing spondylitis

2. Erythema nodosum

3. Uveitis

4. Primary sclerosing cholangitis (more often than with CD)

5. Strong association with cancer. Risk highest in patients with pancolitis of 10+ years duration (20-30 fold increased risk compared to age-matched population)

Front 387

Malabsorption Syndromes

Back 387

1. Whipple disease

2. Disaccharidase (lactase) deficiency or absence

3. Abetalipoproteinemia (acanthocytosis)

4. Celiac sprue

5. Tropical sprue

Front 388

Whipple Disease

Back 388

1. Rare

2. Malabsorption with chronic osmotic steatorrhea and weight loss

3. Macrophages loaded with Periodic acid-Schiff positive rod-shaped bacilli (Tropheryma whippelii) accumulate predominantly in the proximal small intestinal mucosa, which has a gross appearance of white surface discoloration
a. Also found in lymph nodes (causing lymphadenopathy), synovial membranes (polyarthritis), and brain (obscure CNS symptoms)
b. Arthropathy (any disease affecting joints) is commonly the initial presentation.

4. Predominantly found in Caucasians with a strong male predominance (10:1)
a. Typical patient: white male in his 30s-40s

5. Responds quickly to antibiotic therapy (the difficulty is diagnosing it)

Front 389

Disaccharidase (lactase) deficiency or absence

Back 389

1. Common

2. Incomplete breakdown of lactose causes osmotic diarrhea and excessive intestinal gas

3. Can be:
a. Congenital (rare, with symptoms on initiation of milk feeding)
b. Acquired (common, with incidence increasing with age)
i. Particularly frequent among descendants of cultures more recently introduced to dairy farming (Asians, African Americans, Hispanics, Native Americans)
ii. As we age, we lose some ability to metabolize lactose.

4. LYN: Lactose hydrogen breast test—bacterial fermentation leads to increased hydrogen production that can be measured in exhaled air by gas chromatography

Front 390

Abetalipoproteinemia (acanthocytosis)

Back 390

1. Rare

2. Autosomal recessive inability to synthesize apolipoprotein B**
a. Complete absence of lipoproteins that contain apolipoprotein B—chylomicrons, VLDL, LDL
b. Free fatty acids and monoglycerides enter the enterocytes, are re-esterified, but cannot be assembled into chylomicrons
i. Results in vacuolation of enterocytes and steatorrhea**
ii. Small intestine appears frothy.

3. Manifest in infancy as failure to thrive, diarrhea, and steatorrhea

4. Lipid membrane abnormalities result in acanthocytic erythrocytes** (burr cells)
a. Spiky RBCs on peripheral smear

Front 391

Celiac sprue

Back 391

1. aka Celiac disease, gluten-sensitive enteropathy, non-tropical sprue

2. Hereditary intolerance to gluten-derived dietary proteins (in wheat, rye, barley, oat), particularly the gliadin fraction
a. Rice and corn proteins are not toxic
b. Gluten toxicity causes secondary small intestinal injury, leading to malabsorption
i. **Morphology: marked villous atrophy with hyperplastic and elongated crypts (overall mucosal thickness unchanged; small intestine resembles colon)
ii. More marked in the proximal small intestine than distal because the duodenum and jejunum are exposed to the highest concentration of dietary gluten

3. Demographics: largely in whites; rare to nonexistent in native Africans, Japanese, and Chinese

4. Diagnosis uses circulating antibodies (anti-gliadin; anti-endomysial; anti-tissue translutaminase)

5. Malabsorption symptoms and intestinal lesions reverts after gluten exclusion from the diet
a. Patients who adhere to a gluten-free diet remain well

Front 392

Celiac Sprue
(etiologies)

Back 392

1. Cell-mediated immunity, especially sensitized intramucosal T cells
i. Increased intraepithelial cytotoxic T cells
ii. Increased lamina propria helper T cells sensitized to gliadin

2. Genetic predisposition—95% of patients express HLA-DQw2, HLA-DR3 on chromosome 6

3. Adenovirus (cross-reactivity of gliadin with a fragment of the E1b protein of type 12 adenovirus)

Front 393

Celiac Sprue
(associations)

Back 393

1. Dermatitis herpetiforumis**—chronic, blistering disease of the skin by a symmetric itching eruption of vesicles and papules that occur in groups; relapses are common

2. Long-term risk of malignant disease
i. Intestinal lymphomas, particularly T cell lymphomas**
• Contrast with the fact that most intestinal lymphomas originate from B-cells
ii. GI, particularly esophageal squamous cell, carcinoma
iii. Breast cancers

Front 394

Tropical Sprue

Back 394

1. (post-infectious sprue)

2. Malabsorption within days of acute diarrheal enteric infection
a. Injury evident at all levels of the small intestine (contrast with proximal involvement in celiac sprue)

3. Frequently causes folate and vitamin B12 deficiency--> megaloblastic change

4. Seen in people living in or visiting the tropics, but no specific causal agent identified
a. Epidemic outbreaks, endemic forms
b. Enterotoxigenic organisms have been implicated

5. Treatment: broad-spectrum antibiotics, folate, vitamin B12

Front 395

Other malabsorptive etiologies to remember

Back 395

1. pancreatic insufficiency,

2. biliary obstruction,

3. Crohn disease,

4. short bowel syndrome

Front 396

Vascular Disorders

Back 396

1. Ischemic Bowel Disease

2. Angiodysplasia

3. Hemorrhoids

Front 397

Ischemic Bowel Disease Classifications

Back 397

1. occlusive v. Non-occlusive

2. Transmural(gangrenous) v. Nontransmural (non-gangrenous)

3. Acute v. Subacute/Chronic

4. Small intestine v. Colonic

Front 398

Ischemic Bowel Disease
(Occlusive)

Back 398

1. Arterial^: thrombotic or embolic
(emboli usually arise from thrombi
of left side of heart)
i. Affected area usually sharply defined

2. Venous^: thrombotic
i. Affected area fades into adjacent bowel

Front 399

Ischemic Bowel Disease
(Non-occlusive)

Back 399

Caused by shock, as seen in toxic pathology

Front 400

Ischemic Bowel Disease
[Transmural (gangrenous)]

Back 400

1. Acute total occlusion of large vessels
caused by sudden complete occlusion of the
celiac trunk, superior mesenteric artery,
or inferior mesenteric artery

2. Involves all layers of the bowel

Front 401

Ischemic Bowel Disease
[Non-transmural (non-gangrenous)]

Back 401

1. Insidious or incomplete occlusion of large vessels
or
Occlusion of smaller vessels
(“flea bites of hemorrhage” grossly)

2. Superficial bowel affected; gross lesions may be absent.


3. Mural infarction involves the mucosa and submucosa;


4. Mucosal infarction extends only to mucosa.

Front 402

Ischemic Bowel Disease
(Acute)

Back 402

1. Sudden, complete occlusion of large vessels

2. Often results in transmural infarction

3. Sudden, severe abdominal pain

4. Sudden bowel evacuation of bloody stools

5. Possible perforation

6. Rapid shock and vascular collapse
(within hours of onset)

7. High mortality (50-75%)

Front 403

Ischemic Bowel Disease
(Subacute/Chronic)

Back 403

1. Insidious, partial occlusion of small vessels

2. No visible effect
or
Non-transmural infarction

3. Intermittent episodes of bloody diarrhea, mimicking IBD

4. Mostly seen in elderly, more difficult to diagnose.

Front 404

Ischemic Bowel Disease
(Small Intestinal v. Colonic)

Back 404

Colonic is more common

Front 405

Ischemic Bowel Disease
(Important points)

Back 405

1. ^Regardless of whether arterial or venous, bowel infarctions appear hemorrhagic because of blood re-flow into the damaged area through numerous collaterals

2. `Compared to the small intestine, the colon has fewer collaterals, less arterial blood supply, and greater intraluminal pressure.
i. **Two colonic areas are particularly vulnerable to ischemic injury: the splenic flexure (most exposed; watershed of the SMA and inferior mesenteric a.) and the cecum
ii. Case: older individual with bloody diarrhea? investigate ischemic bowel disease (likely not inflammatory because of elderly age at onset), especially at the splenic flexure

Front 406

Angiodysplasia

Back 406

1. Tortuous dilations of the submucosal and mucosal blood vessels in the cecum and/or right colon
a. Ectatic (dilated) veins, venules, and capillaries can bleed easily.

2. Attributed to:
a. Wall tension
i. LaPlace’s law—tension in the wall of a cylinder is a function of intraluminal pressure and diameter
• The cecum has the widest diameter of the colon, so it develops the greatest wall tension.
b. Vascular degenerative changes relating to aging (after 50s) and possibly genetics
i. Most patients are older than 60 years

3. Causes 20% of all significant lower intestinal bleeding**
a. Bleeding may be chronic/intermittent or acute/massive
b. Dilated vascular channels may be separated from the intestinal lumen by only the vascular wall and attenuated epithelial cells, hence the propensity for bleeding

4. Treatment: cauterization of bleeding areas

Front 407

Hemorrhoids

Back 407

1. variceal dilatations of the anorectal venous plexuses

2. Classification
a. external
b. internal
c. mixed/Combined

3. Predisposing influences:
a. Low fiber diet, constipation, long periods sitting, obesity, venous stasis of pregnancy,
b. Rarely, hemorrhoids reflect collateral anastomotic channels developing due to portal hypertension

Front 408

External Hemorrhoids

Back 408

1. involve the inferior hemorrhoidal plexus, below the anorectal (dentate/pectinate) line; somatically innervated

2. Complication: painful thrombosis after an episode of constipation or in young individuals related to heavy exercise
• Treatment: surgical excision if pain does not subside after 48 hours

3. Not prone to bleeding due to squamous epithelium covering**

Front 409

Internal Hemorrhoids

Back 409

1. superior hemorrhoidal plexus; viscerally innervated

2. Complications are nonpainful bleeding and prolapse
• Treatment: diet modification, banding, infrared coagulation, electrocoagulation, hemorrhoidectomy

3. Colonic mucosal covering

4. More prone to bleeding due to columnar epithelium

Front 410

Mixed/Combined Hemorrhoids

Back 410

both plexuses are affected

Front 411

Colonic diverticula (diverticulosis)

Back 411

1. Acquired, false (only involve herniation of the mucosa and submucosa and NOT the muscular layers) diverticula of the colon which bulge out into the serosa [Slides 4 and 5]

2. Occur through weak points (where the vasa recta penetrate the inner circular layer of smooth muscle) alongside the taenia coli (outer longitudinal bands of smooth muscle of the colon)

3. In general, most cases of diverticulosis are asymptomatic or present with non-specific symptoms

4. Complications that arise in about 10-25% of individuals include
a. (most common) inflammation (diverticulitis); associated with obesity and red meat consumption
b. (in more serious cases) involves perforation of the colon; perforation would lead to peritonitis, pericolonic abscesses, fistulas, and/or sepsis
c. hemorrhage (usually occurs in diverticula originating on the right side of the colon); a total colectomy required in situations of uncontrollable bleeding

5. In western societies, since diverticulosis generally occurs on the left side, symptoms will simulate a "left-sided appendicitis"

Front 412

Colonic diverticula
(Epidemiology)

Back 412

1. Very prevalent; frequency increases with age, low fiber diets, diets higher in red meats, and low physical activities

2. More common in western, industrialized societies; in these societies, diverticula commonly occur in the left distal colon (sigmond and descending colon) and rarely occurs in the rectum

3. In Asian and non-industrialized societies, diverticula (in the rare instances when seen) are found in the right colon (commonly the cecum)
a. Find right side diverticula in certain patient populations -->particularly in the cecum

Front 413

Mechanical Intestinal Obstruction

Back 413

A. A clinical syndrome with the following symptoms

1. Colic

2. Distention of the abdomen

3. Vomiting

4. Failure to pass feces or gas

Front 414

Four Most common Causes of Intestinal Obstruction

Back 414

1. Hernias
2. Intestinal adhesions
3. Intestinal intussusception
4. Volvulus

*account for 80% of all obstructions

* masses (benign or malignant) can also cause obstruction

Front 415

Hernias

Back 415

1. protrusions (usually a loop of bowel) through a weak point in the peritoneal wall that end up in a pouch (hernial sac) formed by the peritoneal lining and protruded soft tissue

2. Types
a. Inguinal hernia
b. Umbilical hernias
c. Femoral hernias
d. Obturator hernias
e. Incisional hernias (iatrogenic)

Front 416

Inguinal Hernias

Back 416

1. Most common type in both men and women;

2. more common in men (9:1)

3. Types: Direct and indirect or combined

Front 417

Direct inguinal hernias

Back 417

1. above the inguinal ligament,

2. pass medially to the inferior epigastric vessels;

3. do not go through the deep inguinal ring but instead push through layers of transversalis fascia to enter the inguinal canal;

4. do not end up in the spermatic cord

5. Occurs above the inguinal ligament

Front 418

Indirect inguinal hernias

Back 418

1. make up 75% of all inguinal hernias)

2. occur along the inguinal canal;

3. do pass through the deep inguinal ring,

4. lateral to the inferior epigastric vessels;

5. actually do end up in the spermatic cord

Front 419

Umbilical hernias

Back 419

1. Most are congenital;

2. commonly seen in infants;

3. involve protrusions into umbilicus

4. Most of these are small and close spontaneously by the age of 4-5 years

Front 420

Femoral hernias

Back 420

1. Pass through femoral canal medial to femoral vein

2. Will notice these in the upper medial portion of the thigh

3. Femoral hernias occur almost exclusively in females (HOWEVER inguinal hernias are the more common type of hernias that occur in females)

4. Since the femoral canal is very narrow, these are prone to incarcerate (get stuck) and then strangulate (compromise vascular supply)

Front 421

Obturator hernias

Back 421

1. Pass through the obturator canal

2. Are NOT palpable nor are visible externally thus may present as an intestinal obstruction of unknown cause

3. More common in women than men (6:1)

Front 422

Incisional hernias (iatrogenic)

Back 422

1. Breakdown of surgical sutures with the intestines herniating through the open incision

Front 423

Hernias, in general, can be

Back 423

i. Reducible
ii. Incarcerated
iii. Strangulated

Front 424

Reducible

Back 424

the intestines can be replaced, either manually or spontaneously

Front 425

Incarcerated

Back 425

the hernias are no longer reducible (stuck)

Front 426

Strangulated

Back 426

the vascular supply is compromised and infraction is occurring; a surgical emergency
• Risk of Gangrene

Front 427

Intestinal adhesions

Back 427

1. can also cause intestinal obstruction, and are relatively common

2. These are fibrous bands that form between two intestinal loops, OR between an intestinal loop and the abdominal wall

3. Mostly complications of previous surgeries, infection, or endometriosis

4. On rare occasions, can be congenital (called Ladd bands) and are associated with malrotation

5. Most are secondary to
i. Previous surgeries
ii. Infections
iii. endometriosis

6. Any kind of inflammation in the abdominal cavity can cause adhesions
i. Commonly caused by endometriosis

7. Can result in volvulus, obstruction, and strangulation

Front 428

endometriosis

Back 428

occurs when the endometrial glands and stroma are found in areas outside of the uterus; this abnormality can happen anywhere in the abdominal cavity, though commonly in lower abdomen and pelvis

Front 429

Intestinal intussusception

Back 429

1. when a section of intestine telescopes into the immediately distal segment;

2. can be extensive in that it can extend all the way to the anus

3. leading point is the portion of intestines that telescopes most distally inside the other porti

4. Most common cause of intestinal obstruction in young children, especially male infants

5. Often occurs in the terminal ileum in two different ways
i. Ileo-ileal - a part of the ileum telescopes into another part of the ileum
ii. Ileo-colic - the terminal ileum telescopes into the cecum

6. Associated symptoms
i. Colic
ii. "Currant jelly" stools - classic description of jelly-like, red, mucoid stools
iii. Any symptoms that result from general intestinal obstruction

Front 430

Intestinal intussusception
(causes)

Back 430

1. idiopathic in general;

2. it has been speculated that the leading point may actually be the areas of the ileum that have lymphoid hyperplasia;
i. recall that children have prominent lymphoid follicles (Peyer's patches) in the terminal ileum;
ii. these areas when exposed to vaccinations or viral infections are prone to lymphoid hyperplasia which may somehow result in intussusception

3. On the rare occasion intussusception occurs in adults:
i. The leading point may be either a polyp in the lumen, a tumor, or an enlarged lymph node
ii. May result in intestinal obstruction and strangulation (trapping of mesenteric vessels)

Front 431

Volvulus

Back 431

1. a twisting of the intestines ≥180 degrees along the mesenteric axis [slide 17]

2. Results in obstruction and infarction; also strangulation

3. Occurs in the mobile parts of the colon (ex. sigmoid and cecum, and even in transverse colon); this commonly occurs in elderly people, most likely due to constipation

4. In newborn and infants, the small intestine is the more common site; commonly caused by Meckel's diverticulum OR adhesions

5. Types
i. Gastric volvulus
ii. Colonic (sigmoid, cecum)
iii. Small intestine

Front 432

Gastric volvulus

Back 432

1. occurs in adults in cases of a hiatal hernia of the paraesophageal (rolling) type

2. a small intestine volvulus

Front 433

Colonic Volvulus

Back 433

1. (sigmoid, cecum)

2. Elderly

3. Constipation

Front 434

Small intestine Volvulus
(children)

Back 434

• Malrotation (mid-gut volvulus) the most common volvulus
• Meckel diverticulum
• Adhesions

Front 435

Tumors of the Intestines

Back 435

1. Polyps
2. Colorectal Adenocarcinoma
3. Carcinoid tumors
4. Gastrointestinal lymphomas

Front 436

Polyps (Classifications)

Back 436

1. sessile, which lack a stem (pedicle)

2. OR pedunculated, which have a stem

Front 437

non-neoplastic (non pre-malignant) polyps
(types)

Back 437

1. Inflammatory polyps

2. Hyperplastic polyps

3. Hamartomatous polyps

Front 438

Inflammatory polyps

Back 438

1. Not that common

2. Are considered pseudopolyps since they are non-neoplastic

3. Formed by granulation tissue and hyerplastic epithelium reacting to an inflammatory insult

4. Macroscopically - look like polypoid mass

Front 439

Hyperplastic polyps

Back 439

1. hyperplasia of the intestinal crypts

2. Very common (more common in men),

3. and are usually small (<5 mm) and sessile

4. Have glandular lumens that have star-shaped, or serrated profiles which is the hallmark of hyperplastic polyps
i. Have hyperplasia of the mucosa

5. Prevalence increases with age

6. Locations are similar to those of adenomatous polyps (ex. the sigmoid and rectum)

7. Most of these are asymptomatic and are found incidentally; rarely are they large enough to cause a problem

8. Though these are classified as non-neoplastic and generally have no significant malignant potential, there is some controversy associated with the classification as some (including Dr. Ruiz) feel that these polyps may progress to malignancy

Front 440

Hamartomatous polyps

Back 440

1. hamartomas are proliferation of structures in the tissue of its origin

2. Types
i. Juvenile polyps (or retention polyps)
ii. Peutz-Jeghers polyps

Front 441

Juvenile polpys
(Retention polyps)

Back 441

1. Cystically dilated glands;

2. abundant stroma disproportionate to the number of glands

3. Are often large, inflamed, pedunculated, and have a smooth, non-lobulated surface that is usually ulcerated

4. You have a lot of inflammation on the surface, which results in the ulceration

5. Sporadic and single

6. Most occur in rectum

7. Have no malignant potential

8. Majority occur in children < 5 years old

9. Most occur in the rectum
- will present with bright red blood either during or after a bowel movement

10. Rarely multiple

Front 442

Melena

Back 442

1. black feces

2. Because the blood has been exposed to gastric digestive juices
i. so bleeding is proximal to stomach

Front 443

When Juvenile polyps are Multiple

Back 443

1. part of an autosomal dominant syndrome called juvenile polyposis;

2. these patients do have a higher risk for colorectal adenocarcinoma

Front 444

Hematochezia

Back 444

more distal GI bleeding that has not been exposed to gastric acids and appears bright red

Front 445

Peutz-Jeghers polyps

Back 445

1. another Harmatomatous polyps

2. Have an arborizing (branching) proliferation (seen histologically) of the muscularis mucosae

3. Are large and pedunculated; the cap of the polyp, UNLIKE the juvenile polyps, is lobulated; also their epithelium is usually NOT ulcerated

4. Like the juvenile polyps, can be single or a few and sporadic

Front 446

Multiple Peutz-Jeghers polyps

Back 446

1. part of the autosomal dominant Peutz-Jeghers syndrome

2. Involves mutations in the STK11 tumor suppressor gene

3. These patients have multiple polyps in the jejunum and ileum, and also (less commonly) in the duodenum, stomach, and colon

4. Can also have pigmented macules (lentigo, lentigines, lentiginosis) in the lips, oral mucosa, genitalia, palms of hands, soles of feet, and the face;
i. these can be very discrete so be observant;
ii. tend to fade as kids grow older;
iii. in elderly people may only occur in oral cavities

5. The patients with this syndrome have increased risk of carcinomas in areas OTHER THAN the GI tract such as the lung, pancreas, breast, testicle, ovary and uterus;
i. while there many be an increased risk of malignancy in the digestive tract (esophageal and gastrointestinal carcinomas), the risk in the aforementioned regions are more significant

Front 447

Neoplastic polyps with pre-malignant potential

Back 447

1. Adenomatous polyps

2. Serrated adenomas

Front 448

Adenomatous polyps

Back 448

1. By definition are dysplastic polyps;

2. can have varying degrees of dyplasia
i. in low-grade dyplasia, nuclei are small and are at the basement membrane, and plenty of goblet cells are present;
ii. at higher grades, the nuclei increase in size and begin to pseudostratify and pile up

3. Can be sessile or pedunculated

4. Most occur in the colon
i. Occur in the small intestine on one occasion
• in the periampullary region of the duodenum;
• generally the small intestine, despite its large size, seems to be protected against adenomatous polyps and adenocarcinomas

5. More frequent in men; prevalence increases with age; most are asymptomatic

6. Most adenocarcinomas arise from adenomatous polyps; the malignant transformation takes many years allowing for the chance for intervention; importance of screening; risk of malignancy depends on size of polyp and whether it is villous or tubular
i. If entirely tubular and <1 cm, low risk for cancer
ii. If >4 cm and is villous, 40% risk for cancer

7. Carcinogenesis is slow

Front 449

Adenomatous polyps
(subtypes)

Back 449

i. tubular (the most common type)
• glands are essentially round
• can be pedunculated or sessile

ii. villous (with long villous projections; are generally large and sessile)

iii. tubulovillous (a combination of tubular and villous)
• the more villous the polyp the greater the risk of already having an adenocarcinoma

Front 450

Serrated adenomas

Back 450

1. relatively new concept that is generally disregarded by physicians

2. Combine features of adenomatous polyps and hyperplastic polyps

3. These are becoming more important due to their link to a specific carcinoma that develops in the proximal (right) colon, especially due to increased incidence of right sided colon cancers (though left sided colon cancers are still more prevalent);

4. it is postulated that a carcinoma that is proximal to the splenic flexure may be more related to serrated adenomas than one that is distal

Front 451

Familial adenomatous polyposis (FAP)

Back 451

1. An autosomal dominant disease syndrome that is common in our community

2. Occurs when a patient has more than 100 adenomatous polyps in their colon at a young age; at least 100 polyps are necessary to be considered the classic syndrome

3. Linked to a gene on chromosome 5 called adenomatous polyposis coli gene (APC)
a. Defect in APC gene 5q21

4. The mutation in this gene is thought to be one of the first steps in carcinoma development

5. Polyps are not limited to the colon, but can also be found in the periampullary area of the duodenum, and even the stomach

6. Progression to adenocarcinoma [Slides 40 and 41] is nearly 100%; patients usually undergo a prophylactic colectomy around 19-20 years of age to prevent cancer from developing

7. An attenuated type of FAP presents with about 30 polyps located mostly in the proximal colon, with a lifetime cancer risk of 50% [LYN]

Front 452

Colorectal Adenocarcinoma
(incidence and mortality)

Back 452

1. Third in incidence in males behind prostate and lung cancer

2. Third in incidence in females behind breast and lung cancer

3. Second in mortality in males behind prostate

4. Third in mortality in females behind breast and lung cancer

Front 453

Colorectal Adenocarcinoma
(risk Factors)

Back 453

1. Frequency increases with age, peaking at 60-79 years

2. Associated with excess caloric intake, obesity and decreased physical activity; these are generally factors seen in societies of higher socio-economic status and that are more urbanized

3. Colorectal cancer is also associated with a high intake of animal fat, and proteins (associated with red OR white meat consumption)

4. Also associated with a decreased intake of folate and calcium

5. Smoking increases the risk of colorectal adenocarcinoma and adenomatous polyps

6. Alcohol intake also increases the risk of cancer, mainly in the rectum

7. Colorectal adenocarcinoma is also associated with inflammatory bowel disease (IBS)

8. Polyposis syndromes and chromosomal abnormalities may also be risk factors

Front 454

Primary prevention of colorectal cancer

Back 454

1. Decrease caloric intake, stop smoking, stop drinking alcohol, etc.

2. Taking NSAIDS such as aspirin, piroxicam, and sulindac
a. These drugs have been shown to prevent the emergence of polyps and regress polyps
b. The downside is that these drugs also increase the risk of GI bleeding and cardiovascular events

3. Fiber, fruits, and vegetables may help prevent colorectal cancer, but not as strongly as the NSAIDs

4. Providing post-menopausal hormonal supplements (estrogen AND progesterone) for women can decrease risk of cancer; the downside is these hormones can lead to an increased risk for endometrial cancer, breast cancer, thromboembolism, and coronary heart disease

5. Removal of polyps:

Front 455

Secondary prevention (early detection)

Back 455

1. Fecal occult blood test, yearly

2. Fecal DNA test, yearly

3. Sigmoidoscopy, every 5 years

4. Double-contrast barium enema , every 5 yaers

5. CT colonography (virtual colonoscopy, every 5 years

6. Colonoscopy every 10 years

Front 456

REMEMBER, adenomatous polyps can lead to adenocarcinoma

Back 456

1. The prevalence of adenomatous polyps mirrors that of colorectal cancer

2. The anatomical distribution of adenomatous polyps is comparable to that of colorectal cancer

3. The peak incidence of adenomatous polyps comes before (about 10 years earlier) the peak incidence for colorectal cancer, allowing time for intervention

4. Early invasive carcinoma is often surrounded by adenomatous tissue

5. The risk of cancer is directly related to the number of adenomatous polyps

6. Removal of adenomatous polyps reduces the incidence of colorectal cancer

7. Much more common in distal (left) colon, though now also found in right colon

Front 457

Multi-hit concept of Carcinogenesis

Back 457

1. The APC/Beta-catenin pathway (suppressor pathway)

2. The microsatellite instability pathway and Hereditary Non-polyposis Colorectal Cancer (HNPCC, Lynch Syndrome)

Front 458

The APC/Beta-catenin pathway (suppressor pathway)

Back 458

1. Hypothesis - an accumulation of mutations that lead to malignancy

2. steps:
i. The APC gene is lost (same gene affected in FAP described above)
ii. Followed by beta-catenin mutations
iii. Then K-ras genes are activated
iv. SMAD genes are then lost
v. Then p53 is lost
vi. Telomerases are then activated

Front 459

The microsatellite instability pathway and Hereditary Non-polyposis Colorectal Cancer (HNPCC, Lynch Syndrome)

Back 459

1. This pathway is not as frequent

2. This has to do with carcinomas that are proximal to splenic flexure (right-sided); possible association with serrated adenomas

3. The process goes like this:
i. Starts with defect of DNA mismatch repair genes
ii. This defect in DNA mismatch repair genes results in microsatellite instability

4. In general, this pathway is associated with the autosomal dominant condition called hereditary non-polyposis colorectal cancer syndrome (Lynch Syndrome); occurs more often in right colon
i. This is also associated with extra-intestinal cancers, in particular, endometrial cancer
ii. Called NON polyposis because originally it was thought that these carcinomas developed without polyps; now there is shown to be a link to the serrated adenomas (discussed above)
iii. The cancers caused by this syndrome occur at a young age

Front 460

trends of colorectal cancer

Back 460

1. Incidence
i. Incidence is higher in men than women
ii. Though no major racial differences between whites and blacks in terms of incidence, there has been a decreased incidence in white males which may lead to a racial difference in incidence eventually; while the decrease in incidence in whites is occurring in all anatomical areas, it is mainly seen in left-sided sigmoid and rectal cancers
2. Mortality
a. Mortality is greater in men than in women
b. More mortality in blacks than whites
c. Mortality in whites is decreasing in both males and females (again, in carcinomas located on the left side such as the sigmoid, rectum)

Front 461

Left-sided cancer vs. right-sided colorectal cancer

Back 461

1. Right-sided cancer is more common among African Americans, and elderly individuals; thus it is important to recommend colonoscopies, not just sigmoidoscopies

2. Anatomic differences
a. Location of carcinomas are related to different molecular events (the two pathways above), and also to different morphologies

Front 462

Right-sided colorectal tumors

Back 462

1. Carcinomas in the cecum and proximal colon are more exophytic in that they grow INTO the lumen, and outwards;

2. the right sided colon is more voluminous than the left resulting in less likely occurrence of obstruction

3. Generally result in the loss of a small amount of blood and the patient will probably present with mild anemia; detect with an occult blood test

Front 463

Left-sided colorectal tumors

Back 463

i. Are more endophytic, infiltrative
ii. Are more annular (circle around the circumference of the colon rather than protrude into it)
iii. The term apple core, or napkin ring, describes the radiographic appearance of these cancers as the lumen gets smaller
iv. Obstruction commonly result; and patients will present with a change in bowel habits
v. Bleeding in is very common (but not in left-sided diverticula)
vi. Worse prognosis than right-sided cancers

Front 464

Iron-deficiency anemia and colorectal cancer, VERY IMPORTANT CONCEPT

Back 464

a. In an elderly man presents with iron-deficiency anemia, GI cancer considered initially
b. In an elderly woman, uterine bleeding should be considered before colorectal cancer

Front 465

Markers for colorectal cancer

Back 465

carcinoembryonic antigen (CEA); can also be used as a marker in other cancers

b. Used for monitoring patients with resected colon cancer NOT for diagnosis

Front 466

Prognosis determinants of colorectal cancer

Back 466

a. The most important factor in prognosis is the stage, how widespread the tumor is
b. Evaluate local lymph nodes, other organs, etc. in order to stage colorectal cancer (TMN system)
c. There are many systems designed to stage cancers, the system designed for colorectal cancers is the Duke's system

Front 467

Carcinoid tumors

Back 467

1. are common in the stomach and are associated with hypergastrinemia

2. Develop from neuroendocrine cells such as the enterochromaffin cells of Kulchitsky

3. Majority arise in the gastrointestinal tract, but can also arise from lungs (second most common), liver, bile ducts, pancreas, or ovary

4. In the GI tract, mostly found in the ileum (since cancers rarely develop in the small intestine except in the periampullary area of the duodenum, a tumor found here is most likely a carcinoid one) and appendix (usually found in the tip); less often seen in stomach, colon, and rectum

5. Are yellow-tan in color AFTER fixation

6. Are SUBMUCOSAL (intramural); do not usually affect the mucosa (generally intact) or cause ulceration [Slide 60]

7. The cells are monotypic (very monotonous and very similar to each other); can be arranged in discrete islands, trabeculae, or glands; can look like plasma cells

Front 468

Carcinoid tumor growth

Back 468

1. grow very indolently, they are capable of metastasizing and invading; size and deep local penetration correlates with metastasis;

2. small bowel carcinomas are most often associated with metastasis

3. If tumor is ≥2 cm and is penetrating deeply, has potential to metastasize (80% chance)

4. Carcinoids in the appendix or rectum, despite appearance, very rarely metastasize

5. Carcinoids in the ileum do metastasize (very slowly) and may lead to death

Front 469

Substances produced by carcinoids

Back 469

1. Serotonin (5-hydroxytryptamine) and other histamine-like substances

2. These substances normally go into the circulation and are removed or inactivated by the liver

Front 470

Carcinoid syndrome

Back 470

occurs when the liver is overwhelmed with products secreted by carcinoid tumors

2. Can occur when tumors are very large, resulting in overproduction of these substances

3. Can also occur when they metastasize to the liver, compromising normal liver function

4. Also occurs when the tumor is located outside the portal system, thus the venous supply from that organ does not drain immediately into the liver

5. Symptoms
i. Vasomotor disturbances like flush
ii. Intestinal hypermotility resulting in diarrhea, cramps, nausea, vomiting
iii. Broncho-constrictive attacks (similar to an asthma attack)
iv. Pulmonic and tricuspid valve thickening
v. Endocardial fibrosis (mainly in the right ventricle)

Front 471

Carcinoid Tumors
(Prognosis)

Back 471

1. Prognosis is excellent with no metastases

2. Even with metastases to the liver and with carcinoid syndrome, prognosis is promising (10-15 years)

Front 472

Gastrointestinal lymphomas

Back 472

1. Lymphomas of mucosa-associated lymphoid tissues, MALTOMAS;

2. can be low or high grade

3. GI tract is the most common location for primary, extranodal lymphomas (the ones that originate in the lymph nodes); the most common location in the GI tract is the stomach and also the small bowel

4. Most of the primary GI lymphomas are of the B-cell type (>95% of them all)

5. GI T-cell lymphoma is associated with celiac-sprue and are located in the proximal small bowel; are very aggressive and have poor prognosis

6. They destroy glandular structures, break into the muscular layers, and eventually metastasize

Front 473

Gastrointestinal lymphomas
(risk factors)

Back 473

1. Helicobacter pylori - depend on cytokines produced by H. pylori reactive T-helper cells to stimulate growth; antibiotics can be used to remove this infection, allowing for regression of cancer (in some instances, not all)

2. Immunocompromised patients, particularly HIV+ patients, are at an increased risk

3. To reiterate, celiac disease is a risk factor for GI T-cell lymphomas

Front 474

Gastrointestinal lymphomas
(Prognosis)

Back 474

1. In general, prognosis is better than normal lymphomas, with the gastric lymphomas having the best prognosis
a. Better than nodal
b. Better than intestinal or coloic

2. T-cell lymphomas have poor prognosis

3. Grade and stage (more important) of dissemination are major determinants of prognosis

Front 475

Mediterranean Lymphoma

Back 475

1. Immunoproliferative small intestinal disease (IPSD) - a massive infiltration of lymphocytes and plasma cells in the proximal small intestine mostly; overt B-cell lymphoma

2. Cause malabsorption and diarrhea

3. Associated with Campylobacter jejuni; antibiotics has occassionaly shown regression of the cancer

4. Associated with a specific type of immunoglobulin, IgA, with a heavy chain that is truncated in the variable portion and devoid of a light chain; also called "Alpha heavy chain disease"

5. Endemic in Middle East and Mediterranean

Front 476

Diseases of the appendix

Back 476

1. Acute appendicitis

2. Mucoceles of the appendix

Front 477

Acute Appendicitis

Back 477

1. This is very frequent

2. It mostly affects young adults (possibly due to prominence of lymphoid structures in the area), and mostly young men (1.4: 1)

3. Most common cause is obstruction from a fecalith, a piece of feces occluding the lumen of the appendix; some other cases involve obstruction due to seeds, etc.

4. Inflammation in the muscularis propria is diagnostic

5. Appendicitis is more common in west because of low fiber diets

6.Histologically, must see neutrophils in the mucosa, submucosa, muscularis propria, serosa

7. Complications
a. Rupture; this can result in suppurative peritonitis
b. Pylephlebitis or inflammation of the portal vein; this can result in thrombosis of the vein, liver abscesses, and general portal hypertension

Front 478

Mucoceles of the appendix

Back 478

1. cystic dilatation of the appendix by inspissated (thickened) mucus

2. Rare; can be caused by obstruction of the appendix

3. 25% of cases results from a hyperplastic epithelium or polyp that secretes copious amounts of mucin into the lumen creating distention of the appendix

4. 60% of cases are caused by (benign) mucinous cystadenomas which similar to a common ovarian neoplasm; cause the greatest dilatation of the appendix;

5. 20% of mucinous cystadenomas have mucus that permeate the appendix and then extravasate into the abdominal cavity resulting in a condition called pseudomyxoma peritonei where patients present with distended abdomens full of massive amounts of mucoid material

Front 479

mucinous cystadenocarcinomas

Back 479

1. Malignant counterpart to mucinous cystadenomas

2. account for 10-15% of mucocele cases;

3. mucus AND malignant cells permeate the wall of the appendix;

4. this condition is also called pseudomyxoma peritonei

Front 480

pseudomyxoma peritonei

Back 480

1. used to describe both the benign and malignant conditions;

2. in general, a very serious condition that is difficult to control;

3. if it is malignant, it can consistently recur and cause intestinal obstruction which can lead to death;

4. even the benign form can lead to death

Front 481

Liver Functional Reserve

Back 481

80-90% of the organ must be lost before insufficiency ensues. Consequently, many processes remain subclinical for long periods of time.

Front 482

Liver Functions

Back 482

1. Metabolism
2. Protein synthesis
3. Detoxification
4. Bile excretion

Front 483

Liver function tests

Back 483

1. Serum proteins-most serum proteins are produced by the liver
a. Total and albumin (both should be diminished in liver disease)

2. Coagulation factors
a. Prothrombin time (PT)-prolonged in disease; impairment in the synthesis of coagulation factors II, VII, IX and X (has to do with vitamin K, we will see why this is later)

3. Aminotransferases
a. Aspartate (AST), alanine (ALT)-Liver damage causes these enzymes to be released so there is an increase in the levels of these enzymes with hepatcellular damage.

4. Alkaline phosphatase (ALP) and Gamma-glutamyl transpeptidase (GGT)
a. ALP and GGT are stored in the bile ducts, so when there is damage to the liver their levels will increase.

5. Bilirubin (increased in disease)

Front 484

Liver
(Anatomic Considerations)

Back 484

1. Enlargement of the liver
a. Normal adult weight: 1,400-1,600 gm
b. Normal (percussion, palpatory) span:
i. Midclavicular line: 6-12 cm
ii. Midsternal line: 4-8 cm
iii. You must perform both procedures to measure the liver. Why is this important? In diseases like emphysema the diaphragm is pushed downwards, but there is no hepatomegaly.

c. In a normal adult the liver should not protrude 2 cm or more below the costal margin.

d. If you can palpate the liver, the patient may already have a tumor or cirrhosis although he/she may be asymptomatic.

e. Often, there is accompanying splenomegaly with hepatomegaly.

Front 485

Hepatic microarchitecture

Back 485

1. Lobules – centered on terminal hepatic venules (central venules) with portal triads (hepatic artery, portal vein, and bile duct) at the periphery.

2. Acini – zone 1 (peripheral or periportal), 2 (midzonal area), 3 (pericentral or centrilobular
a. Acinar zone 3 is most susceptible to toxins, hypoxia, and shock.
b. Although Zone 1 is the first to be exposed to toxins, it is not necessarily the most susceptible b/c Zone 3 contains the enzymes that detoxify the toxins and so zone 3 is most susceptible