I. Oral Cavity
Head and Neck Pathology
Fluoride
Gingivitis (Inflammation of gums)
Swollen Gums
Periodontitis
*Aphthous Ulcer
Glossitis
Macroglossia
Makes enamel resistant to degradation by
bacterial acids by forming Fluoroapatite.
Accumulation of Dental Plaque:
1) Normal oral flora
2) salivary protein
3) desquamated epithelial cells
Calculus (calcified plaque)
1) Phenytoin (anti-epileptic)
2) AML-M5 (Acute Monoblastic or Monocytic
Leukemia)
+ periodontitis
Infl. of periodontal ligament, cementum and
alveolar bone. Can lead to teeth loss/distant
infection (heart, lung, brain)
Can be assoc. w/ many IC dz.s
Causative org: Actinobacillus, Actinomycetes
Painful, single lesion, related to stress
Atrophy, not true infl.
1) B12 Deficiency-Pernicious Anemia
2) Kawasaki Dz
3) Plummer-Vinson Syndrome (GWAC)
ChildrenCretinism (Congenital
Hypothyroid)—presents at birth as large,
protruding tongue
Adults Amyloidosis
HSV
Multiple vesicular lesions
Candida
IC pt (Diabetes, chemo, HIV) can be scraped off
Erythema Multiforme
Steven-Johnson Syndrome
Pregnancy
Ludwig Angina
Rendu-Osler Weber Syndrome
Melanotic Pigmentation involving oral cavity:
Causes =
Maculopapular, vesiculobullous eruption that
occurs AROUND the mouth, not inside
Lesions look like targets.
Due to: Abx or Mycoplasma
Maculopapular, vesiculobullous eruption
involving mucosal surface of lips and cheeks
Ex) Prev. hx strep/pneumo + Abx Tx
Pyogenic granuloma—red, friable
Complication of Pancytopenia involv. extension
of severe oral inf. to the NECKCellulitis
Severe oral inf.—gingivitis, pharyngitis, tonsillitis
Autodom. disorder w/ mult. congenital
aneurysmal telangiectasis beneath mucosal surf
of oral cavity and lips. May have vesicular lesions
in brain Seizures
1. Addison Disease
2. Peutz-Jegher Syndrome + Mult. Polyps
3. Fibrous Dysplasia of Bone-Albright Snd
4. Hemochromatosis (Liver)
Hairy Leukoplakia
Tumor-Leukoplakia
Tumor-Erythroplakia
Squamous Cell Carcinoma
IC pt. Lateral border of tongue. Hyperkeratotic.
Can NOT be scraped off. Dysplasia, Malignancy.
Organism: EBV
Precancerous—ventral(under) surface of tongue.
Thickening of epithelium in Gingiva (white
plaques)—4 diff. presentations.
Can NOT be scraped off.
Inflammation and Vasodilation
Dysplastic lesion
Tobacco and HPV
3 Stages: 1) Hyperplasia/Hyperkeratosis
2) Moderate Dysplasia (p53 mutation)—Inc. N:C,
pre-malginant
3) SCC—disorderly cells entire thick, invade BM
II. Nose and Sinuses
Nasal Polyps
Sinusitis
Kartagener Syndrome
Wegner’s Granulomatosis
Necrotizing Lesions—Nose and URT
Squamous papillomas
Squamous Cell Carcinoma
Hyperplastic glands w/ Infl.
Due to recurrent rhinitis
Organisms: Bacteria EXCEPT in Diabetics
Mucormycosis
Due to chronic rhinitis/tooth infection
Sinusitis, situs inversus, Bronchiectasis, defective
or inadequate cilia + infertile M
Sinusitis, pneumocystis, glomerulitis
cANCA
Mucormycosis, Wegener, Extranodal NK T Cell
Lymphoma
Benign tumors of Nasopharynx
HPV 6, 11
Malignant tumor of Nasopharynx
AfricaChildren, AsiaAdults, rare in US
EBV found in tumor cells
Squamous cells in lymphoid background
III. Larynx
Laryngitis
Squamous Papillomas
Squamous Cell Carcinoma
Serious Form: Haemophilus Influenzae in
children. Can lead to Epiglossitis suffocation
from airway obstruction
Occur on TRUE vocal cords, no sequelae
Adults—Solitary lesion
Children—Multiple, recur, linked w/ HPV 6,11
KEY RF: Tobacco, gen. appear on vocal cord
Persistent Hoarseness for months
Late sx: Dysphagia, pain, hemoptysis (necrosis)
IV. Neck
Branchial Cyst
Thyroglossal duct cyst
Paraganglioma
Lateral, second branchial arch remnant
Midline, remnant of thyroid descent tract
Benign tumor w/ Neurosecretory
Carotid body, SNS and PSNS
V. Salivary Gland
Sial Adenitis
Chronic Sialadentiis
Anti-Ro in pregnancy
Pleomorphic Adenoma
Warthin Tumor
Oncocytic Cells
Mucoepidermoid Carcinoma
Mumps (RNA virus)
Children—No Sequelae
Adults Pancreatitis, Orchitis
Sjogren Syndrome
Risk of Lymphoma in salivary galnds
Anti-La (SSA) and Anti-RO (SSB)
High risk intrauterine heart block of fetus
Myoepithelial cells embedded in myxoid stroma
First Presentation Facial Nerve Palsy
Benign, most common (90%) tumor of salivary
gland, recurs; commonly in Parotid
Benign, Parotid; low recurrence (diff. from PA)
M>F, 40-60 yo, Smokers
Gross: encapsulated mass w/ cystic spaces
Micro: Benign Glands lined by double layer of
oncocytic cells surr. a lymphoid stroma
Cells w/ large number of mitochondria on EM
Malignant (most common malig.)-maj. Parotid
Gross: Large, poor circumscribed, mucinous
Miro: Squamous islets, mucous glandular struct.
Prognosis dep. on GRADE (90 v 50% survival)
Esophagus Pathology
Plummer-Vinson Syndrome
Achalasia
Chagas Disease
Food sticking in throat
Sliding Hiatal Hernia
Paraesophageal/Rolling Hiatal Hernia
Zenker Diverticulum
(Pharyngoesophageal)
Epiphrenic Diverticulum
Mallory-Weiss Syndrome
Boerhaave Syndrome
Esophageal Varices Pathogenesis
Reflux Esophagitis (GERD)
Upper webs, Iron Deficiency Anemia
(Microcytic), Glossitis and Cheilosis
Risk of post-cricoid Carcinoma
Partial or incomplete relax. of LES on
swallowing w/ increased resting tone
Biopsy: diminished myenteric ganglia in
body of esophagus/around LES
S/Sx: Progressive dysphagia
Sequelae: 5%-->Squamous Cell Carcinoma
Secondary Chagas Disease
Due to: Trypanosoma Cruzi
S/Sx: Achalasia, toxic megacolon, dilated
cardiomyopathy
Achalasia or Carcinoma
95% of All, Cardia herniates upward
(straight up—one line w/ esophagus)
Gen. Greater curvature herniates alongside
esophagus
Associated w/ previous surgery (operation
for sliding HH)
Sequelae: Strangulation or obstruction
Above the UES
Etiology: cricopharyngeal motor dysfx w/ or
w/o GERD and decreased lumen of UES
Accumulates food Regurgitation,
dysphagia, NECK MASS, aspiration pneumo
Above LES—due to discord. peristalsis/LES
relaxation
*Nocturnal regurgitation of lots of fluid
LONGITUDINAL tears of mucosa at EG jx
Bleeding that resolves
Alcoholics or with severe vomiting
Can penetrate mucosa
Complete perforation of the esophagus
assoc. w/ M-W syndrome
S/Sx: Pain radiating to back
Severe/prolonged portal HTDilated veins
beneath mucosa at Gastro-Esophageal
Anastomoses: Coronary V.s in stomach and
Plexi in distal esophagus
IF >5mm RuptureLife-Threat Hemorr.
(Hematemesis)
(50% of deaths in pt w/ adv. cirrhosis)
40-50% pt die in 1st bleeding episode
Most common cause, Adults >40yo
Etiology: sliding HH, Dec. LES tone
Inadequate or slowed esophageal clearance
of refluxed material  Achalasia
Reflux Esophagitis Micro
Reflux Esophagitis Clinical S/Sx
Relfux Esophagitis Clinical Outcomes
Barrett Esophagus
Barrett Esophagus Clinical Features
Herpes Esophagitis
Candida Esophagitis
Squamous Cell Carcinoma
SCC Pathogenesis
SCC Morphology
(same for Esophagus and Gastric
Carcinoma)
SCC Micro
Adenocarcinoma
Adenocarcinoma Appearance
Adenocarcinoma Clinical Sx
Infl. cells in epithelial layer
(neutrophils/Lymphocytes), basal zone
hyperplasia
Severity of sx does NOT correlate to degree
of histo changes
Heartburn, regurg. of sour brash, dysphagia
Severe: Hematemesis, Melena
Healing or Bleeding
Complications: Ulceration, stricture, Barrett
Esophagus ( Adenocarcinoma)
Metaplastic Change: SquamousColumnar
in LOWER esophagus
Complication of chronic GERD
Gross: Red, velvety appearance
Dx requires:
1) Endoscopy—columnar epi above GE jx
2) Biopsy—Intestinal Metaplasia
MOST Imp. RF for Adenocarcinoma
40-60 yo, White, M>F
30-40x Risk of Adenocarcinoma w >3cm BE
Multiple punched-out ulcers that occur
along ENTIRE length of esophagus
Occur in immunosuppressed pt
Dirty/gray pseudomemb. appearance
Immunosupp. or diabetics
Most common site: Middle 1/3
Adults > 50yo, M>F
Blacks, Asians, and US increased risk—diet ,
Alcohol, tobacco, nitrosamines
Poor prognosis due to insidious onset
can recur local and distally
Chronic EsophagitisDysplasiaCancer
Can metastasize to regional nodes or spread
by lymphatics locally
1) Exophytic/Protruded—60%
2) Flat (infiltrative)—15%
3) Excavated (necrotic ulceration)—25%
can fistulate into trachea or aorta
Pleomorphic, hypochromatic, large nuclei
w/ prominent nucleoli. Pink collagen in
cytoplasm. (signs of malignancy)
>40 yo, median of 60 yo, M>F, White>Black
p53 over-expression in Barrett
Esophagus or p53 functional inactivation
Lower 1/3 of esophagus
Start as flat/raised patchesLarge nodules
or infiltrate and ulcerate
Most prod. mucin—Intestinal-type Epi
Dysphagia, wt loss, hemorrhage, CP, vomit
Poor prog. in general, > if superfic./resected
Stomach Pathology
Structure
Cells
Heterotopic Rests (Congenital)
Diaphragmatic Hernia
Pyloric Stenosis
Acute Gastritis Pathogenesis
Acute Gastritis Assoc.
Chronic Gastritis
Chronic Antral Gastritis
Atrophic/Autoimmune Gastritis
Granulomatous Gastritis
GVHD Gastritis
Fx of PG Synthesis by Mucosal Cells
Peptic Ulcer
Cardia—Mucous Cells
Fundus-Parietal Cells and Chief Cells
Antrum—Muscous Cells and G Cells
G Cells-Endocrine-Gastrin
EcL-Produce Histamine
D Cells-produce Somatostatin
Mucous Cells-prod. Mucus and Pesinogen II
Parietal Cells—IF and HCl secretion
Many mitochondria, eosinophilic
Chief Cells: Pepsinogen I and II
Tissue that doesn’t belong there
Pancreatic—pylorusinflObstruction
Gastric—DuodenumulcerBleeding
Gastric—Upper EsophagusInfl., discomf.
Defective closure, gen. on left. Asx or
Respiratory problems in newborn
Congenital hypertrophy of musc. propria
Projectile vomiting at 2-3 weeks of age
Assoc. w/ Turner Syndrome, atresia; M>F
PE: palpable mass—feels like olive and
visible peristalsis
Together or individually:
↑Acid secr&Back diffusion + ↓ Bicarb buffer
+ ↓ blood flow  Disruption of mucus layer
or direct mucosal inj  Acute gastritis
1) AlcoholicsMassive Hemorrhage
2) Aspirin for RA, may bleed
Atrophy and metaplasia (w/o erosions)
Dysplasia  Neoplasia = complication
Due to H. Pylori (G- curved rods)
Hypochlorhydria NOT Anemia/Achlor.
↑Risk Gastric Carcinoma and Lymphoma
Diffuse damage of Body and Fundus
mucosa
Autoimmune: Ab to Parietal Cells, Gastrin
R, IF, and H+/K+ ATPase
Anti-ParietalPernicious Anemia +
Achlorhydria
↑Risk Gastric Carcinoma & Carcinoid
Crohn’s Disease or Idiopathic
Erosion of gastric mucosa
1) ↑ mucus and Bicarb. prod.
2) Vasodil., improved mucosal blood flow
3) Inhibit acid secr. by Parietal Cells
Breach in mucosa that extends into
submucosa or deeper
H. Pylori Duodenum and Stomach
Chronic, relapsing, Solitary EXCEPT in
Zollinger-Ellison Syndrome
H. Pylori Characteristics
H. Pylori Diseases
Pangastritis
Acute Gastric Ulceration
(NOT peptic ulcers)
Hypertrophic Gastropathy – 4 Types
1. Menetrier’s Disease
(Protein-losing gastropathy)
2. Parietal Cell Hypertrophy
Hyperplastic Polyp—Benign
Adenoma (Adenomatous Polyp)
Gastric Carcinoma
(50-60% in Pylorus and Antrum)
Risk Factors for Gastric Carcinoma
Zollinger-Ellison Syndrome
Complications: Bleeding, Perforation,
Obstruction from edema and scarring
Multiple ulcers of stomach and duodenum +
Diarrhea
Tumors of pancreas produce gastrin
(Gastrinoma) + Parietal Cells to secrete
HCl and Peristalsis
UreaseAmmonia and CO2 (Buffers gastric
acid) and Toxic compounds (NH4Cl)
PhospholipaseDamages surf. epith.
ProteinsImmunogenic
Adhesins
Mobility
Chronic gastritis, peptic ulcer, gastric
carcinoma, MALT lymphoma
High IL18 , PangastritisAtrophyCancer
Multiple lesions = erosions and ulcers
1. Curling Ulcers – assoc. w/ severe burns or
trauma, located in proximal Duodenum
2. Cushing Ulcers – assoc. w/ intracranial
injury, occur in stomach, duod., esoph. &
high incidence of perforation
Mucosal epithelial hyperplasiaelargement
/hyptertrophy of gastric rugae
Can MIMIC: infiltrative carcinoma/
lymphoma on physical exam
Excess acid secr. assoc↑risk peptic ulcer
Males 40-60 yo
Hyperplasia mucous cells, atrophy of glands
 Excess mucous and little acid in gastric
secretionsProtein loss = Hypoproteinemia
Assoc. w/ chronic use of acid secretion
inhibitors (Proton Pump Inhibitors)
Get: Parietal cell hypertrophy w/o excess
acid!
Common in chronic gastritis, NO malignant
potential—Req. Biopsy to diff. from Adeno
Proliferative dysplasia of epi w/ Malignant
potential. Gen. Single and in Antrum
Assoc w/ chronic gastritis w/ intestinal
metaplasia
90-95% malignant tumors of stomach
Japan, SA inc. risk due to salt in diet
Very Poor Prognosis
Linitis Plastica—leather bottle
Environmental—Nitrites (food)
Host—Chronic atrophic gastritis
Genetic: Blood Group A, FMHx
CDH1 and BRCA2Diffuse gastric cancer
Morphology of Gastric Carcinoma
Early Gastric Carcinoma
Advanced Gastric Carcinoma
Intestinal Type Carcinoma
Gastric Type Carcinoma
Gastric Carcinoma Clinical
Krukenberg Tumors
Virchow’s Nodes
MALT Lymphoma
Gastrointestinal Stromal Tumor
Carcinoid Tumors
Exophytic, Flat/depressed,
Excavated/Ulcerative—heaped up, beaded
margins and necrotic base (diff. from
chronic peptic ulcer which is well
demarcated, punched out lesion)
Confined to: Mucosa and Submucosa
regardless of LN met
Extending below submucosa into muscle,
regardless of LN met
Glandular, expansile growth
Mutations in β Catenin and APC
Infiltrating pattern of poorly diff. cells +
Signet ring conformation , Gastric-type
mucus cells that don’t form glands but
permeate the wall as indiv. cells or clusters
Insidious, Asx until late-wt loss, abd p,
anorexia, vomiting, altered bowel habits
Hemorrhage may occur due to necrosis
Metastasis to ovaries (In GC)
Metastasis to L Supraclavicular Node
often First clinical manifestation of GC
t11;18
Stomach is most common site for extranodal
lymphoma—EBV assoc. too
Mutation of gene encoding tyrosine kinase
cKIT
Most commonly in SI (Small bowel)
Gen. older adults-50-65 yo
Triad: Diarrhea, Flushing, Asthma
May hear tricuspid murmur via thickening
Dx Test: 5-HIAA (Breakdown of Serotonin)
Small Intestine Pathology
Blood Supply to SI
Special Glands of Duodenum
Heterotopia
Atresia -congenital
Stenosis-congenital
Meckel Diverticulum -congenital
Secretory diarrhea
Osmotic Diarrhea
Exudative Diarrhea
Rotavirus
Norwalk Virus
GVHD esp. bone marrow transplant
Radiation
Malabs. snd most common in US
Key Sx of Malabs:
Celiac Disease –Gluten-sensitivity
Required for Dx of Celiac Disease
Dermatitis Herpetiformis
Whipple Disease Malabs.
1. Duodenum – Gastroduodenal and SMA
2. Rest of SI Superior Mesenteric A.
Brunner’s Glands—Submucosal
Congenital Anomaly—gen. Pancreaticinfl.
maybe gastriculcers
Duodenal atresia most common
May be acquired via intussusception
Failure of vitelline duct (gut to yolk sac) to
involute. True Diverticulum. Heterotopic
rests in 50%. May see bleeding if ulcer.
Isotonic, >500mL/day. Rotavirus, E. Coli,
Cholera, villus adenomas, laxatives, VIPoma
>500mL/d, osmolality >plasma by 50mosm
Lactase deficiency, antacids
Purulent, bloody stool=Shigella, Salmonella
Outbreaks in infants
Outbreaks in school children and adults
Focal crypt cell necrosis Severe, watery
diarrhea
Endothelial cell inj.-->Ischemic fibrosis and
stricture.
Acute: Anorexia, cramping, malabs.
Chronic: Inflammatory enteritis
Pancreatic insuff., Celiac Sprue, Crohn’s
Anemia—B12, folate
Petechiae—Vitamin C
Skin Problems—Vitamin E (dermatitis)
Bone Pain/tetany--Calcium
Chronic, mucosal lesion of SI = malabs.
Caucasians, improves w/ remove wheat
HLA-DQ2 and DQ8
Anti-Gliadin or Anti-Endomysial AbIgA
T-Cell mediated HS (CD8, CD4+Gliadin)
Gross: flat mucosa
LM: marked atrophy of villi
*HIGH RISK OF LYMPHOMA
Malabs sx, SI biopsy, sx improve w/o gluten
*Dermatitis Herpetiformis
*Granular IgA deposit in dermal papillae
Vesicular lesions on extensor surfaces only
Systemic Disease-CNS, joints, GI
Trophyrema Whippeli (G+ actinomycete)
White, middle-aged Males
*Lamina propria laden w/ distended
MΦs PAS+ Rods
Lymphadenopathy + Hyperpigmentation
of skin, joint problems 1st sign
Abetalipoproteinemia
Infants: failure to thrive, steatorrhea
Inborn error of metab. (AR)
Ischemic bowel disease
Incarceration in hernia
Strangulation in hernia
Intussusception
Adenoma
Def. of β-Lipoprotein req. for transport of
intestinal chylomicrons.
↑TG Enterocyte Vacuolation
↓ LDL, VLDL, CM Acanthocytes (Burr
cells)
Histo: Coagulative necrosis
Transmural = Poor prognosis – perforation
quickly, sudden severe abd. P!, N/V/D/M
Edema from impaired Venous drainage
Compromised Arterial & Venous—infarct
Infants/ Young kids: Currant-Jelly Stool
Adults: neoplasms
Benign, Ampulla of Vater (obstructive
jaundice)
40-70 yo, maj. in Duodenum
Major RF: Infl. from Celiac Disease
↑ in familial polyposis
Clinical: Occult blood
FOR Small Intestine—UWORLD
LM Finding of intestinal Mucosa
1. marked atrophy of intestinal villi Celiac Disease
2. Distended MΦs in intestinal lamina propriaWhipple Disease
3. collections of neutrophils in crypt lumina Ulcerative Colitis
4. Intestinal infl. w/ scattered non-caseating granulomas Crohn Disease
5. massive infiltration of intestinal lamina propria w/ atypical lymphocytes
Gastrointestinal Lymphoma
Large Intestine Pathology
Blood Supply
(Know for vignettes assoc w/ thrombosis)
Hirschprung Disease
Pseudomembranous Colitis
Crohn’s Disease (IBD)
Ulcerative Colitis (IBD)
Crohn’s Disease
Ulcerative Colitis
IBD (Both)
Crohn’s Key Sx:
UC Key Sx:
Key Complications of Crohn’s
Key Complications of UC
Extra-Intestinal Manifestations of Crohn’s
Ascending/Proximal Transverse – Superior
Mesenteric A.
Rest of Colon to rectum – Inf. MA
Upper Rectum – Superior Hemorrhoidal A.
(off IMA)
Lower Rectum – Hemorrhoidal br.s off
Internal Pudendal A.
Absence of ganglion cells (Auerbach’s
and Meissner’s) in part of GI
Neural crest cell migration defect
Dilation proximal to aganglionic segment
Meconium Ileus—failure to pass meconium
in infants
C. Diff, can be w/o abx after surgery or
debilitating illness, + Exotoxins A,B,C
Plaque-like adhesions w/ fibrinopurulentnecrotic debris and mucus, adherent to
damaged mucosa.
Granulomatous infl. that can be found ANY
part of GI, esp. Ileum. Transmural Infl..
Skip Lesions. Ulcers, fissures.
*Non-Caseating Granuloma ↓ Th cells in
periphery = ↑risk viral and fungal inf.
String Sign on X-Ray(narrowed lumen)
Nongranulomatous, confined to
Colon/rectum. Superficial continuous
Infl(mucosa).
Ulcers, Pseudopolyps. *Crypt Abscesses
Cobblestones
HLA-DR1/DQw5
pANCA
HLA-DR2
HLA-B27 Ankylosing Spondylitis
AND inflammation is FINAL common
pathway
Diarrhea/fever/P! separated in time, may be
precipitated by stress
Bloody, mucoid, diarrhea-relapsing after
mo. to decade and persists days to months
Strictures
Fistulas
Malabsorption + Protein-Losing enteropathy
↑Risk cancer w/ pancolitis
Toxic Megacolon
Erythema Nodosum
Migratory Polyarthritis
Sacroilitis
Extra-Intestinal Manifestations of UC
Angiodysplasia
Peutz Jeghers Syndrome
Villous Adenoma
Familial Adenomatous Polyposis (FAP)
Gardner Snd
Turcot Snd
Multiple Hit for Adenoma-Carcinoma
Lynch Syndrome (HNPCC)
Adenocarcinoma =98% colon cancer
Carcinoid Tumor
Carcinoid Snd Sx:
Acute Appendicitis
Mucinous Cystadenocarcinoma in Appendix
Ankylosing Spondylitis
Primary Sclerosing Cholangitis (pANCA)
Clubbing of fingers
Uveitis, arthritis, DVT, pyoderma
gangrenosum, ankylosing spondylitis
Tortuous dil. of sumuc/muc BV
Sx: Hematochezia
Melanotic change incl. mouth + Polyps
Increased risk carcinoma of pancreas and
ovary NOT colon.
Increased risk of cancer
Hypokalemia—due to inc. SA for fluid secr.
APC gene on Chromosome 5
(Adenomatous polyposis coli)
Adenomatous polyps that carpet mucosa
Clinical: Presents in teens-20s
ALL have Adenocarcinoma in 10-15y
FAP + Osteoma (Mandible/skull/long bone)
Polyposis of colon + Gliomas
1st Hit—Abnormal APC
2nd Hit: Loss of normal APC
3rd hit: KRAS mutation
4th Hit: Inactivationg of p53 =Adenoma
DNA Mismatch Repair defect
60-79 yo
If in young: must suspect Hx of UC or
Polyposis snd.
55% Rectosigmoid
Proximal colon more dangerous, larger
lumen, meaning no obstruction until late.
Any pt >50yo w/ microcytic anemia (Iron
def. anemia)—GI cancer until proven
otherwise
Liver is primary site of met
Appendix MC site (w/ obstruction) then SI
RARELY met, but if so it’s extensive, to liver
= carcinoid Snd
Gross: Solid yellow/tan
Carcinoid Snd: 5-HIAA in urine and blood
(breakdown of serotonin)
Good prognosis if not spread
Flushing, hypermotile GI, Bronchoconstr.,
hepatomegaly, systemic fibrosis, tricuspid
murmur
MCC: Obstruction via fecolith. pinworms too.
Mainly Adolesc., young adults
Dx: NΦ in muscularis
Pseudomyxoma peirtoneii (mucin in
peritoneal cavity w/ rupture of appendix)
Liver Pathology
Jaundice
Unconjugated Hyperbilirubinemia
Hemolysis
Familial Unconj. Hyperbilirubinemia
Anemia + ↑LDH1 + ↓Haptoglobin + ↑Retic
Crigler-Najjar
2
3
↑LDH1 (Pre-hepatic)
1
Fatal
↓ Activity, Live
Gilbert Snd.
LDH1 specific to RBCs
Mut. of UGT
Promoter
Conjugated Hyperbilirubinemia
80% Direct Bilirubin
Obstruction
Familial Conjugated Hyperbilirubinemia
Extrahepatic
Intrahepatic
CA head of Pancreas
OR
Primary Sclerosing
Cholangitis
(pANCA )
CA of Ampulla of Vater
OR
Direct Bilirubin >5
Alk Phosphatase >500
Primary Biliary Cirrhosis
(Anti-Mitochondrial
Antibodies)
OR
Cholestasis in Pregnancy
Direct Bilirubin <5
Alk Phosphatase <500
Rotor
Dubin Johnson
Black Liver
Mixed Hyperbilirubinemia
Unconjugated
50%
Conjugated
50%
Parenchymal Disease
Hepatitis
Autoimmune
Infectious
Hepatitis B
Serology
Hepatitis A
Type I
Type II
Anti-SMA
Anti-KLM
Serology
Elevated Liver Enzymes:
ALT + AST+ LDH5
(In 1,000s due to necrosis)
Elevated Liver Enzymes:
ALT + AST +LDH5
(In 1,000s due to necrosis)
NOT Alk phosphatase
(No obstruction)
NOT Alk phosphatase
(No obstruction)
Heme Metabolism
Drug that impairs Bilirubin uptake in liver
Elevated Unconjugated Bilirubin
Elevated Conjugated Bilirubin
Elevated 50/50
LDH
Hepatocyte Integrity
Biliary Excretory Function
Hepatocyte Function
Acute Hepatic Failure
Chronic Hepatic Failure
Sx of Hepatic Failure
Hyperestrogenemia sx
Cause of Hepatorenal snd?
Morphology of Acute Viral Hepatitis
Hepatitis A (ssRNA-Picorna-N)
Hepatitis B (dsDNA-Hepadna-E)
HemeBiliverdin (Heme Oxygenase)
BiliverdinBilirubin (Biliverdin Reductase)
-Unconjugated BilirubinRifampin (may prevent binding to anion
binding protein)
Pre-hepatic problem
Obstruction
Parenchymal liver disease (problem with
hepatocytes)
LDH1 – Heart and RBC
LDH3 – Lungs
LDH5 – Liver
Cytosolic hepatocyte Enzymes:
AST, ALT, LDH
Direct Bilirubin
Plasma Membrane Enzymes:
Alkaline Phosphatase –Not specific
Hepatocyte Metabolism:
Serum Ammonia  Hepatic Failure
Proteins secreted into blood ( ↓ ):
Serum Albumin
Factors V, VII, X, PT, Fibrinogen PT Time
 Massive Necrosis
Drugs: Acetaminophen, Halothane, Rifampin
Toxins: Mushrooms, CCl4
Viral Hepatitis: Hep A and B
Caused by Cirrhosis
Cirrhosis requires?
1. Degen. of hepatocytes
2. Regen. of hepatocytes
3. Fibrosis
Jaundice, HYPOalbuminemia,
HYPERammonemia (w/ Hepatic
Encephalopathy), HYPERestrogenemia,
coagulopathies, hepatorenal snd
Palmar erythema, spider angiomas,
hypogonadism and gynecomasti in males
Tubular damage by bile plugs
(Large amt of bilirubin excreted in urine)
Hep B Ground glass hepatocytes (HBsAg)
Hep C Fatty change
Active Hepatitis Ballooning Degeneration
Maybe cholestasis (bile plugs in canaliculi)
Apoptosis Mallory Bodies
2-4 weeks incubation, fecal oral
Dx: IgM Ab  Acute Phase
Can be fulminant, Never chronic
1-4 month incubation,
Blood/Birthing/Baby-making
Dx: HBsAg or HBcAb
Hepatitis B (dsDNA-Hepadna-E)
Hepatitis C (ssRNA-Flavi-E)
Hepatitis E (RNA-Herpes-N)
Hepatitis D (RNA-Delta)
Other causes of Chronic Hepatitis
Major causes of death in Chronic Hepatitis
Auto-Immune Hepatitits
Type I Autoimmune Hepatitis
MCC Chronic Liver Disease
NAFL and NASH
Pathogenesis of NAFL and NASH
Hemochromatosis
Wilson’s Disease
3 Presentations:
1. Acute w/ resolution
2. Chronic - Cirrhosis or Carrier
3. Fulminant Hepatitis Fatal
Inc. Risk Hepatocellular CA
7-8 week incubation,
parenteral/IVD/Cocaine intranasal
Maj. Chronic
Fulminant is VERY rare
Dx: HCV Ab after 3-6 weeks (IgG) –for life
via ELISA or HCV RNA
↑risk Cirrhosis, Carcinoma
4-5 week incubation
High mortality in pregnant F
Dx: PCR, IgM and IgG Ab
Dx: IgM and IgG ab, HDV RNA serum, HDAg
liver
Wilson Dz, alpha-1 AT, Alcoholic, Drugs
(Isoniazid/methyldopa), Autoimm.
Cirrhosis, Liver Failure w/ hepatic
encephalopathy, Massive hematemesis from
varices, hepatocellular CA (HBV-esp.
Neonates or HCV)
Predom. F w/ ↑Risk RA, Thyroiditis, Sjogren,
UC; Elevated IgG; HLA-B8 or Drw3
responds well to anti-infl.
Associated with HLA-DR3
+ANA, SMA, AAA
Solube Ant-liver and Anti-Pancreas Ag Ab
(SLA/LP)
Non-Alcoholic Fatty Liver Disease-3 types
1. Simple hepatic steatosis 2. w/ min. infl.
3. non alcoholic steatohepatitis (NASH)Serious –can lead to cirrhosis
Obesity, Insulin-R/Hyperinsulinemia,
Dyslipidemia, Type II DM
Principal Cause of Cryptogenic Cirrhosis
2 Hit: 1. Hepatic fat accum. 2. oxidative
stress Lipid peroxidation ROSDmg
Due to def. of Hepcidin  deposition of iron
in parenchymal cells
Mutation of HFE (CysTyr = C282Y)
Activates Stellate Cells Collagen
Clinical Triad: Cirrhosis, DM, Bronze Skin
(due to ↑pituitary hormones!)
Also: Arthralgia, ED, Arrhythmia
Accumulation of Copper in tissues: Brain
(Basal Ganglia), Liver hepatocytes, Eye
Dx: Liver Biopsy
Presentation: Adolescent w/ diff. in school,
Alpha-1 Antitrypsin Deficiency
new onset ataxic gait, maybe tremors. Eye
exam shows green-yellow ring around
cornea.
Emphysema and Liver Disease
Histo: PAS + Intrahepatic inclusions
Intrahepatic Biliary Tract Diseases
Primary Sclerosing Cholangitis
Primary Biliary Cirrhosis
Secondary Biliary Cirrhosis
All 3 Lab Findings
M>F, IBD common, Beaded Intrahepatic
Ducts (US), +pANCA
Onion skinning of intrahepatic bile ducts
Sx: pruritis, jaundice, dark urine, light stool,
hepatosplenomegaly
Inc. Risk Extrahepatic bile duct CA
F>M, Autoimmune
Anti-Mitochondrial Ab
Sx: Extreme itching—bile salts in skin
Liver Biopsy: Granulomas around ducts w/
lymphocytic infiltrate in portal tracts
Extrahepatic bile duct obstruction, biliary
atresia, gallstones, stricture, CA of
pancreatic head
Sx: same as PSC
Conjugated Hyperbilirubinemia (obstruct.)
Inc. Alk Phos, Bile Acids, Choleset↑
Extrahepatic: Alk Phos >500, Bili >5
Intrahepatic: Alk Phos <500, Bili <5
Drug Induced Liver Diseases
Injury Pattern
Cholestasis
Morphologic Findings
Bland biliary plugs, no infl
Cholestatic Hepatitis
Cholestasis w/ lobular
necrosis and infl.
Macrovesicular
Steatosis
Steatohepatitis
Microvesicular, Mallory
Bodies
Fibrosis + Cirrhosis
Periportal and pericellular
fibrosis
Noncaseating epitheloid
granulomas
Sinusoidal Obstruction
Syndrome (Venous
occlusion)—Obliteration of
Central Veins
Granulomas
Vascular Lesions
Ex. of Agents
Estrogen (BC, steroids, postmenopause)
Antibioitics
Phenothiazines
ETOH, MTX,
Corticosteroids, Total
Parenteral Nutrition
Amiodarone
ETOH
Tetracycline
MTX, Isoniazid, Enalapril
(Iso is anti-Tb)
Sulfonamides
High Dose Chemo
Neoplasms
Budd-Chiari Syndrome =
Hepatic Vein Thrombosis
--medical emergency w/
severe abdominal pain
Oral Contraceptives
Sinusoidal Dilatation
Oral contraceptives, etc.
Peliosis Hepatis-blood
filled cavities NOT lined by
endothelial cells—can
rupture causing intraabd.
hemorrhage
Hepatic Adenoma
Anabolic steroids,
Tamoxifen
Hepatocellular Carcinoma &
Cholangiocarcinoma
Thorotrast
Angiosarcoma
Thorotrast and Vinyl
Chloride
Oral contraceptives,
Anabolic Steroids
Chronic anemia since childhood assoc. with Budd-Chiari (severe abd P!)—
Paroxysmal Nocturnal Hemoglobinuria
Pathogenesis of hepatic injury in Alcoholic Liver Disease
1. Steatosis due to shunting normal substrates away from catabolism and to lipid biosynthesis due to
1.  generation of NADH by alcohol dehydrogenase and acetaldehyde dehydrogenase;
2. Impaired assembly and secretion of lipoproteins
3.  peripheral catabolism of fat.
2. Induction of cytochrome p-450 that makes other drugs toxic
3. Free radical formation from microsomal ethanol-oxidizing system oxidizes alcohol and they react with cell membranes
4. Alcohol directly toxic to microtubular and mitochondrial function
5. Acetaldehyde induces lipid peroxidation and acetaldehyde-protein adduct formation disrupts cytoskeleton and membrane
Cellular Damage
6. Alcohol induces immunologic attack on hepatic neoantigens,
7. Collagen –Stimulated by inflammatory cytokines or those form Kupffer cells
Morphology:
Definition
Hepatic steatosis = fatty changeReversible if they abstain
alcoholic hepatitis= Necrosis (if continued exposure)  Fatty change and necrosis
cirrhosis = chronic damge  Nodular liver w/ fibrosis
Labs: AST/ALT/LDH –mild elevated; Alk Phos-Miled elevated (<500)
REQUIRES 3 comp: Degen, Regen, Fibrosis
w/ hepatitis + abstinence—resolves and left w/ fatty change
Gamma GtSensitive marker for alcohol exposure (Glutamyl transferase…) –Release is stimulated by alcohol, microsomal enzyme.
Elevated in binge drinking, relapsing alcoholics.
Causes of death are Hepatic coma, massive GI bleed, intercurrent infection, hepatorenal syndrome, hepatocellular carcinoma in
3-6%
Cirrhosis Definition:
1. Bridging fibrous speta- delicate bands of fibrous c.t. replace adjacent lobules
2. Parenchymal nodules – due to regeneration of encircling hepatocytes; small (micronod.)< 3cm – large (macronod.) several cm.
3. Disruption of entire liver architecture
4. Diffuse injury – has to be throughout liver
5. Nodularity – balance between regeneration and scarring
6. Fibrosis – irreversible
7. Vascular architecture reorganized – due to parenchymal injury and scarring, abnormal interconnections between vascular inflow
and hepatic vein outflow channels
Hepatic Dz. In pregnancy
Hepatic Adenoma
Child Malignancy
Adult Malignancy
Hepatocellular CA
Preclampsia and Eclampsia: HELLP Snd
 Hemolysis
 Elevated liver enz.
 Low Platelets
 DIC
Acute fatty liver of pregnancy
 MICROvesicular infiltration
Intrahepatic Cholestasis (Estrogen) -3rd Tri
 Extreme Pruritis
 Dark urine/Pale stool
 Jaundice
Presents w/ Severe RUQ
Assoc. w/ oral contraceptives—young F
Hepatoblastoma—chromosomal del.
Angiosarcoma—Vinyl chloride
Very aggressive
Assoc. w/ cirrhosis related to HBV/HCV
Other cause: Aflatoxins-long standing
consumption of food
Clinical Features: ill-defined
Elevated Serum Alpha-Fetoprotein = HCC
Metastatic Tumors—MCC liver CA
#1 = Colon
#2 = Breast
#3 = Lung
Usually multiple and necrotic
Very few clinical manifestation