Shigella – Pathogenesis
Entry: Invades via M cells overlying ileal Peyer patches
Spread: Accesses basolateral surface → infects enterocytes → spreads cell-to-cell
Damage:
Cell death & ulceration
Bloody, mucoid diarrhea (dysentery)
Aspergillus
Aspergillus species contaminate foods with aflatoxin B1,
a potent hepatocarcinogen that causes characteristic TP53 codon mutations and markedly increases risk of HCC
Pseudomembranous Colitis
Clostridioides difficile colitis
Risk factors
Recent antibiotic use
Hospitalization
Gastric acid suppression (eg, PPI)
Pathogenesis
Disruption of intestinal flora → C difficile overgrowth
Toxin A: Diarrhea (enterotoxin).
Toxin B: Cytotoxic, mucosal necrosis → pseudomembranes.
disrupt cytoskeleton integrity & stimulate inflammation
Pseudomembrane formation IMPORTANTTT
Yellow-white pseudomembranes (neutrophils, fibrin, bacteria, necrotic epithelium).
Clinical presentation
Profuse watery diarrhea (most common)
Leukocytosis (~15,000/mm3)
Fulminant colitis/toxic megacolon IMPORTANTT
Diagnosis IMPORTANTTT
1)) Nucleic Acid Amplification Test (NAAT / PCR)
Detects toxigenic genes (e.g., toxin B gene)
High sensitivity and specificity
Limitation: Cannot differentiate active infection vs colonization
2))Enzyme Immunoassay (EIA)
Detects toxins or bacterial antigens
Toxin EIA: Highly specific but poor sensitivity (needs high toxin levels)
Glutamate dehydrogenase (GDH) EIA: Sensitive but cannot distinguish toxigenic strains
Treatment
Oral fidaxomicin or oral vancomycin
IV metronidazole added for fulminant disease
Normal Gut Flora
> 400 bacterial species in the healthy GI tract.
Facultative anaerobes (~10%): E. coli, Klebsiella, Lactobacillus, Bacillus.
Strict anaerobes (majority): Bacteroides, Fusobacterium.
Suppress pathogens by competing for nutrients and adhesion sites.
Disruption of Microbiome → C. difficile Infection
Causes: Antibiotics, PPIs (gastric acid suppression).
CMV
Cytomegalovirus esophagitis can occur in transplant patients
usually presents with odynophagia or dysphagia that can be accompanied by fever or burning chest pain.
Endoscopy typically shows linear and shallow ulcerations in the lower esophagus,
histology usually shows enlarged cells with intranuclear inclusions.
H. pylori → duodenal vs gastric disease
Microbiology: Motile, spiral, gram‑negative; lives in mucus layer; urease generates ammonia → local alkalinization + epithelial injury; host inflammation adds damage.
Antral‑predominant infection: ↓ somatostatin (D cells) → disinhibited G cells → ↑ gastrin → ↑ parietal cell acid (direct via CCK‑B; indirect via ECL histamine) + ↓ duodenal HCO3− from bacterial toxins → increased acid load to duodenum → duodenal ulcers.
Corpus‑predominant infection: Chronic inflammation → multifocal atrophic gastritis with loss of parietal cells → low/normal acid; delta cells preserved → ulcers from direct mucosal injury/inflammation; higher risk of metaplasia and malignancy (gastric lymphoma, adenocarcinoma).
Key contrasts: Antrum = hyperacidity → duodenal ulcers;
Corpus = hypochlorhydria/mucosal damage → gastric ulcers + cancer risk.
Definition
Extranodal marginal zone B-cell lymphoma involving mucosa-associated lymphoid tissue (MALT).
Arises from post–germinal center memory B cells.
Markers: CD19, CD20, CD22.
Pathogenesis
Chronic immune stimulation (bacterial, viral, or autoimmune).
Most common trigger (stomach): Helicobacter pylori.
HPV AND SCC
Anal squamous cell carcinoma
Risk factors
Human papillomavirus (types 16 & 18)
Receptive anal intercourse
Immunocompromised state (eg, HIV, organ transplant)
Female sex
Smoking
Manifestations
Rectal bleeding/pain, pruritus, mass sensation
Ulcerated or nodular anal mass
Histology
Islands of large, eosinophilic, hyperchromatic squamous cells with scant cytoplasm & nuclear atypia
Prominent keratinization &/or keratin pearls
HHV AND Kaposi sarcoma
Etiology * Endothelial tumor caused by human herpesvirus type 8
* Most common malignancy in patients with untreated HIV
* Endemic in certain African & Mediterranean regions
Manifestations * Cutaneous lesions:
o Violaceous, red, or brown flat lesions → papules
o Most common along skin folds
o Pruritus, pain & friability are rare
o Lymphedema distal to lesions
- Visceral lesions:
o Lungs & gastrointestinal tract most common
o May cause life-threatening bleeding
Histopathology
* Proliferation of spindle-shaped endothelial cells
* Slit-like vascular spaces
* Extravasated red blood cells
HEPATITIS A AND D
Hepatitis A Virus (HAV)
Transmission: Fecal–oral (contaminated water/food, raw or steamed shellfish) IMPORTANT
Incubation: ~30 days
Clinical Features
Acute onset: Malaise, fatigue, anorexia, nausea, vomiting, mild abdominal pain
Key clues: Hepatomegaly, aversion to smoking
Labs: Early ↑ aminotransferases → later ↑ bilirubin & ALP
Marker of active disease: Anti-HAV IgM
Course
Self-limiting (3–6 weeks)
No chronicity: does not progress to chronic hepatitis, cirrhosis, or HCC
hepatitis D virus (HDV):
The hepatitis B surface antigen of hepatitis B virus must coat the hepatitis D antigen of hepatitis D virus before it can infect hepatocytes and multiply.
Hepatitis C AND B
Hepatitis C virus (HCV):
Transmission: Blood-borne; mainly injection drug use, pre-1992 blood transfusions.
Treatment: Direct-acting antivirals (DAAs) targeting specific HCV enzymes:
RNA-dependent RNA polymerase inhibitors (eg, sofosbuvir) – block viral genome replication.
Protease inhibitors (eg, simeprevir) – prevent polyprotein cleavage into functional viral proteins.
NS5A inhibitors (eg, ledipasvir) – block viral replication and assembly.
Genotypes
> 6 genotypes and multiple subgenotypes.
High variability in envelope glycoprotein genes (hypervariable regions).
Replication
No proofreading 3′→5′ exonuclease activity in the RNA-dependent RNA polymerase.
High replication error rate → numerous viral quasispecies within one host.
Clinical Impact
Immune evasion & difficulty developing vaccines.
Chronic infection more likely than with other hepatitis viruses
Hepatitis B Virus (HBV) :
Main Transmission Routes:
Sexual (heterosexual partners, men who have sex with men — most common in developed countries, >70%).
Percutaneous (IV drug use, needlestick, blood transfusions).
Vertical (mother-to-child; more common in high-prevalence areas).
Acute HBV Infection:
Symptoms: Tender hepatomegaly, abnormal liver function tests.
HBsAg present in serum (marker of active infection).
Bacteroides fragilis & Intraabdominal Abscesses
(B. fragilis)
Clinical Context: Perforated appendicitis → intraabdominal abscess (often polymicrobial).
Key Organism: Bacteroides fragilis – anaerobic gram-negative bacillus; part of normal colonic flora.
Unique Feature: Surface polysaccharides promote abscess formation.
Other Common Isolates: E. coli, enterococci, streptococci (all from normal colon flora).
Cryptosporidiosis
Pathogenesis
Fecal-oral transmission (eg, contaminated water, animal contact)
Oocyte ingestion → sporozoite attachment to intestinal epithelium → intraluminal meront formation → fecal oocyte shedding
Clinical manifestations
Immunocompetent: self-resolving, watery (noninflammatory) diarrhea <2 weeks
Immunosuppressed (eg, AIDS, transplant recipient): prolonged, severe diarrhea with weight loss/malabsorption
Diagnosis
Stool PCR testing
Stool microscopy: acid-fast staining oocysts or immunofluorescent assay
Histology: basophilic Cryptosporidium organisms on intestinal brush border, small intestine villous blunting, lamina propria inflammation
Hepatic Abscess
Clinical Clues
Fever, chills, right upper quadrant pain
Fluid-filled liver cavity on imaging
Common Causes
Developing countries: parasitic (e.g., Entamoeba histolytica, Echinococcus)
United States: mostly bacterial (~80%)
Routes of Bacterial Access to Liver
-Biliary tract: ascending cholangitis
-Portal vein: pyemia from bowel/peritoneum
-Hepatic artery: hematogenous spread (e.g., Staphylococcus aureus from distant site)
-Direct extension: peritonitis, cholecystitis
-Penetrating trauma or injury
Schistosomiasis
Hepatosplenic Schistosomiasis
Cause: Parasitic blood fluke infection (Schistosoma species) – common in rural sub-Saharan Africa & East Asia.
Transmission: Contact with freshwater contaminated by infected snails; cercariae penetrate skin → migrate to liver → mature to adults → spread via portal circulation → deposit eggs in venules of bowel/bladder.
Pathogenesis: Chronic egg deposition → activation of hepatic stellate cells → periportal collagen deposition → periportal fibrosis → portal hypertension.
Clinical Features:
Portal hypertension → esophageal varices & splenomegaly.
Anemia (intestinal/variceal bleeding).
Thrombocytopenia (splenic sequestration).
Eosinophilia (response to helminth infection).
Schistosoma species:
1) S haematobium
North Africa
Sub-Saharan Africa
Middle East
Urinary schistosomiasis
Terminal hematuria, dysuria & frequent urination
Hydronephrosis, pyelonephritis & squamous cell carcinoma of the bladder
2) S mansoni
Sub-Saharan Africa
Middle East
South America
Caribbean
Intestinal schistosomiasis
3) S japonicum
Asia, particularly China
Philippines
Japan
BOTH 2 AND 3 :
Diarrhea & abdominal pain
Intestinal ulceration → iron deficiency anemia
Hepatic schistosomiasis
Hepatomegaly, splenomegaly
Periportal fibrosis & subsequent portal hypertension
Chagas disease
Epidemiology
Caused by protozoan Trypanosoma cruzi
Vector: triatomine (“kissing”) bug
Endemic in Central & South America
Cardiac manifestations
Dilated cardiomyopathy with biventricular failure
Apical wall thinning with aneurysm ± mural thrombus
Ventricular arrhythmias
Gastrointestinal manifestations IMPORTANT
Megacolon
Megaesophagus (secondary achalasia) immune-mediated cross-reactivity between the parasite and the enteric ganglia lead to destruction of the submucosal (Meissner) and myenteric (Auerbach) plexus.
Infant botulism
Pathogenesis
Ingestion of Clostridium botulinum spores (eg, environmental dust/soil, honey)
Spores colonize the immature gastrointestinal tract & produce toxin
Toxin inhibits presynaptic acetylcholine release IMPORTANT
Clinical presentation
Age <12 months
Constipation, poor feeding, hypotonia
Oculobulbar palsies (eg, absent gag reflex, ptosis)
Symmetric, descending paralysis
Diagnosis
Classic presentation
Confirmation by stool C botulinum spores or toxin IMPORTANTT
Strongyloides stercoralis
Epidemiology & Transmission
Endemic: Tropical/subtropical areas (Southeast Asia, Africa, Western Pacific)
Transmission: Filariform larvae in contaminated soil penetrate skin (often walking barefoot)
Life Cycle
Skin penetration → bloodstream/lymph → lungs → alveoli → trachea → swallowed
Intestinal stage: Larvae burrow into mucosa, mature into adult worms
Eggs hatch in intestine → rhabditiform larvae (noninfective) → excreted in stool
Autoinfection: Rhabditiform → filariform larvae → reinfect host via intestinal mucosa or perianal skin
Clinical Features
Often asymptomatic
Pulmonary: Dyspnea, wheezing, dry cough
Gastrointestinal: Constipation, diarrhea, abdominal pain
Dermatologic: Linear, pruritic, erythematous streaks (larva currens) on thighs/buttocks
Diagnosis
Serology (IgG): Supports infection, may persist after eradication
Stool: Identification of rhabditiform larvae confirms active infection
Intestinal biopsy: Rarely shows eggs/adults
