Built from GI Lecture 33 (LOs 1–5). Close notes. Fill from memory. Reveal only after a genuine attempt.

LO 1 & 2

ON EXAM — hexagonal classic lobule, portal triad (hepatic a., portal v., bile duct), central vein, zones 1/2/3, directionality of blood flow (triad → central) vs bile flow (hepatocyte → canaliculus → triad), acetaminophen hits zone 3.

Three lobule models

Model	Center	Periphery	Purpose
Classic lobule
Portal lobule
Acinus of Rappaport

Portal triad — 3 components

Structure 1

Structure 2

Structure 3

Hepatocyte on H&E — key features

Cell shape

Nucleus features

Cytoplasm (eosinophilic or basophilic?)

Arrangement (plates/cords)

Two "faces" of hepatocyte

Blood flow directionality

Blood enters at

Blood exits at

Portal vein pressure (mmHg)

Hepatic artery pressure

% of blood from each source

Bile flow directionality (OPPOSITE of blood)

Bile produced by

Collected in

Then to ______ of Hering

Eventually to bile duct at

Zones 1, 2, 3 — function & vulnerabilities

Zone	Location	Key function	Most vulnerable to
Zone 1 (periportal)
Zone 2 (midzonal)
Zone 3 (centrilobular)

Cholangiocytes

What they line

Epithelium type

Secrete (ion) → alkalinize bile

🪤 TRAP: Acetaminophen toxicity, ischemic injury (shock liver), and alcoholic hepatitis all hit ZONE 3 (centrilobular) — it is farthest from oxygenated blood. Zone 1 (periportal) is hit first by viral hepatitis and toxins entering from the portal triad.

LO 3

ON EXAM — discontinuous (sinusoidal) capillary with fenestrations + NO basement membrane, Space of Disse (between hepatocyte and sinusoid endothelium), Kupffer cells = liver macrophages, Ito (hepatic stellate) cells = store vitamin A + become myofibroblasts in cirrhosis.

Hepatic sinusoid — 5 defining features

Feature 1 — endothelium

Feature 2 — basement membrane

Feature 3 — blood mixture

Feature 4 — contained cells

Feature 5 — size/caliber

3 capillary types — compare

Type	Endothelium	Basement membrane	Example organ
Continuous
Fenestrated
Sinusoidal (discontinuous)

Space of Disse (perisinusoidal)

Location (between what 2 things?)

What sits in it (cell type)

Why important (function)

Kupffer cells — 4 functions

Function 1

Function 2

Function 3

Function 4

Cell lineage / origin

Appearance on H&E

Ito (hepatic stellate) cells — quiet vs activated

State	Appearance	Function
Quiet (healthy)
Activated (cirrhosis engine)

Ito cell activation — 6-step cascade in cirrhosis

Step 1 — insult

Step 2 — Kupffer activation

Step 3 — Ito proliferation

Step 4 — transdifferentiation

Step 5 — deposit

Step 6 — consequence

4 clinical consequences of cirrhosis

⚠️ In cirrhosis, activated Ito cells deposit COLLAGEN in the Space of Disse → "capillarization" of sinusoids (they become like regular capillaries WITH basement membrane + no fenestrations) → impaired hepatocyte-blood exchange → portal HTN.

LO 4

ON EXAM — 3-layer wall (NO submucosa, NO muscularis mucosae), simple columnar with microvilli, Rokitansky-Aschoff sinuses = mucosal diverticula, concentrates bile 5–10× by NaCl/H2O reabsorption, CCK triggers contraction + relaxes sphincter of Oddi.

Gallbladder anatomy

Location on liver

3 parts

Cystic duct to where?

Hartmann pouch

3-layer wall (atypical — NO submucosa, NO muscularis mucosae!)

Layer 1 (inner)

Layer 2 (middle)

Layer 3 (outer)

Epithelium

Epithelium type

Surface specializations

Function of microvilli

Rokitansky-Aschoff sinuses

Definition

Pathologic significance (2)

Bile concentration — 4-step mechanism

Step 1 (active transport)

Step 2 (passive movement)

Step 3 (H2O)

Step 4 (net result)

Hepatic bile vs gallbladder bile

Component	Hepatic bile	Gallbladder bile
Volume/concentration
Concentration factor

CCK — 5 functions

Trigger for release

Gallstone types

Stone type	Composition	Risk factor
Cholesterol
Pigment (black)
Pigment (brown)

Acute cholecystitis & porcelain GB

Pathogenesis

Imaging findings

Murphy sign

Porcelain gallbladder — definition/risk

🪤 TRAP: Gallbladder lacks a muscularis mucosae and submucosa. So any mucosal cancer invasion has direct access to the muscularis externa → poor prognosis at diagnosis.

LO 5

ON EXAM — acinar cells (basophilic base, eosinophilic apex = zymogen granules), centroacinar cells begin duct, 4-level duct system (intercalated → intralobular → interlobular → main pancreatic duct), sphincter of Oddi.

Pancreas — quick anatomy

Parts (4)

Retroperitoneal except for...

Main duct name

Accessory duct name

Ampulla = joins bile duct at

Exocrine vs endocrine — % and structure

Component	% of gland	Functional unit	Product
Exocrine
Endocrine

Acinus — histology

Cell shape (arrangement)

Basal cytoplasm (color + why)

Apical cytoplasm (color + contents)

Nucleus location

Zymogen granule contents

Inactive digestive enzymes — 4 examples

Key active enzyme (already active)

Activation — where/how trypsinogen activated

Centroacinar cells

Location

Appearance

Secrete

4-level duct system

Level 1 (smallest)

Level 2

Level 3

Level 4 (largest)

Regulation — secretin vs CCK

Hormone	Trigger	Effect on pancreas
Secretin
CCK

Acute pancreatitis — "pancreas eats itself"

Top 2 causes

Enzyme first activated

Cascade — 3 results

Classic lab findings

Histology findings

LO 5

ON EXAM — islets of Langerhans (pale on H&E), β-cells (insulin, ~70%, central), α-cells (glucagon, ~20%, periphery), δ-cells (somatostatin). T1DM = insulitis + β-cell destruction. T2DM = amyloid deposition. Islet tumors: insulinoma, gastrinoma, glucagonoma, VIPoma, somatostatinoma.

Islet of Langerhans — spotting on H&E

Color relative to acini

Shape

How many/mm²

Location of α vs β cells

Islet cell types

Cell	% of islet	Hormone	Main action
α (alpha)
β (beta)
δ (delta)
PP (F cells)

β-cell insulin release — 5-step cascade

Step 1 — glucose entry

Step 2 — metabolism

Step 3 — ATP closes

Step 4 — depolarization

Step 5 — Ca²⁺ influx triggers

Insulo-acinar portal system

What it is

Why important

Diabetes — histology signatures

Type	Islet histology	Mechanism
T1DM
T2DM

Islet cell tumors

Tumor	Cell of origin	Classic syndrome
Insulinoma
Gastrinoma
Glucagonoma
VIPoma
Somatostatinoma

Pancreatic ductal adenocarcinoma (PDAC)

Location (most common)

Tumor marker

Classic signs (3)

Molecular — most common driver mutation

Prognosis

⚠️ Insulinoma: Whipple triad = (1) symptoms of hypoglycemia, (2) documented low glucose at symptom time, (3) relief with glucose. ↑C-peptide (endogenous) distinguishes from exogenous insulin use.

LOs 1–5

Q1: Liver directionality

In the classic hepatic lobule, what is the direction of blood flow and bile flow, respectively?

A) Both flow from central vein → portal triad
B) Both flow from portal triad → central vein
C) Blood: triad → central vein; Bile: hepatocyte → triad (opposite directions)
D) Blood: central vein → triad; Bile: triad → hepatocyte
E) Both flow in canaliculi

Correct Answer: C

Blood flows INTO the lobule at the portal triad (from hepatic a. + portal v.), through sinusoids, out via central vein → hepatic veins → IVC. Bile flows OPPOSITE — hepatocyte → canaliculus → bile ductule (canals of Hering) → bile duct in portal triad.

Q2: Acetaminophen zone

A 22-year-old woman presents with fulminant hepatic failure after acetaminophen overdose. Biopsy will most likely show necrosis in which region?

A) Zone 1 (periportal)
B) Zone 2 (midzonal)
C) Zone 3 (centrilobular, around central vein)
D) Space of Disse
E) Portal triad

Correct Answer: C

Zone 3 is farthest from oxygenated portal blood → most susceptible to ischemic and toxic injury. Also the zone with the most CYP450 → converts acetaminophen to the toxic NAPQI metabolite. Acetaminophen, ischemia ("shock liver"), and alcohol all target zone 3.

Q3: Sinusoid features

The hepatic sinusoid is classified as which type of capillary?

A) Continuous with tight junctions
B) Fenestrated with intact basement membrane
C) Sinusoidal (discontinuous) — fenestrations + NO basement membrane
D) Lymphatic
E) Arteriole

Correct Answer: C

Hepatic sinusoids are discontinuous capillaries — large fenestrations AND no basement membrane → allows plasma proteins and macromolecules free access to hepatocytes across the Space of Disse.

Q4: Ito cell function

Which cell type, located in the Space of Disse, stores vitamin A in its quiescent state and transforms into collagen-producing myofibroblasts in cirrhosis?

A) Kupffer cell
B) Hepatocyte
C) Cholangiocyte
D) Hepatic stellate (Ito) cell
E) Pit cell (liver NK)

Correct Answer: D

Ito (hepatic stellate) cells — store vitamin A in lipid droplets (why chronic vit A toxicity → ↑ cirrhosis). When activated by Kupffer cell cytokines (TGF-β, PDGF), they transform into myofibroblasts → deposit type I collagen → fibrosis & cirrhosis.

Q5: Gallbladder wall

Which layer is ABSENT from the gallbladder wall (distinguishing it from typical GI tract)?

A) Mucosa
B) Submucosa (and muscularis mucosae)
C) Muscularis externa
D) Serosa
E) Adventitia

Correct Answer: B

The gallbladder lacks a submucosa and muscularis mucosae. It has only 3 layers: mucosa (simple columnar w/ microvilli), muscularis externa, and serosa/adventitia. This means mucosal cancers quickly invade deep — one reason gallbladder adenocarcinoma has such poor prognosis.

Q6: Rokitansky-Aschoff sinuses

A cholecystectomy specimen shows mucosal herniations extending through the muscularis externa. What are these called?

A) Crypts of Lieberkühn
B) Brunner glands
C) Rokitansky-Aschoff sinuses
D) Peyer patches
E) Plicae circulares

Correct Answer: C

Rokitansky-Aschoff sinuses = outpouchings of mucosa through the muscularis externa, characteristic of chronic cholecystitis. Think "cholesterolosis" or gallbladder "diverticula."

Q7: Acinar cell H&E

A pancreatic acinar cell shows intensely BASOPHILIC base and EOSINOPHILIC apex on H&E. What accounts for the basophilia at the base?

A) Zymogen granules
B) Rough endoplasmic reticulum (abundant rRNA)
C) Lipofuscin pigment
D) Mitochondria
E) Glycogen

Correct Answer: B

Basal basophilia = extensive rough ER (for protein/enzyme synthesis) — rRNA is acidic and binds basic dyes. Apical eosinophilia = zymogen granules (pre-packed digestive enzymes). This "polarity" is the hallmark of a serous secretory acinar cell.

Q8: T1DM histology

An autopsy of a 14-year-old boy with a 2-year history of type 1 diabetes shows islets with a lymphocytic infiltrate and profound loss of one cell type. Which cells are destroyed?

A) α-cells (glucagon)
B) β-cells (insulin)
C) δ-cells (somatostatin)
D) PP cells (pancreatic polypeptide)
E) Acinar cells

Correct Answer: B

Type 1 DM = autoimmune destruction of β-cells → insulitis (lymphocytic infiltrate, especially CD8+ T cells). α, δ, and PP cells preserved. Type 2 DM → amyloid deposition (islet amyloid polypeptide / amylin) within islets, β-cell dysfunction.

Q9: Zollinger-Ellison

A patient has refractory peptic ulcers in unusual locations (e.g., jejunum), chronic diarrhea, and elevated serum gastrin. Which islet cell tumor is responsible?

A) Insulinoma (β-cell)
B) Gastrinoma (non-β islet / duodenal)
C) Glucagonoma (α-cell)
D) VIPoma
E) Somatostatinoma

Correct Answer: B

Zollinger-Ellison syndrome = gastrinoma (often duodenal wall or pancreas), causing hypergastrinemia → ↑ gastric acid → multiple, recurrent, distally located ulcers + diarrhea. ~25% of gastrinomas occur in MEN1 (3 P's: Pituitary, Parathyroid, Pancreas).

Q10: PDAC molecular

A 68-year-old smoker presents with painless jaundice, weight loss, and a mass in the pancreatic head. Which is the most commonly mutated oncogene in pancreatic ductal adenocarcinoma?

A) BRAF V600E
B) KRAS
C) EGFR
D) APC
E) BCR-ABL

Correct Answer: B

KRAS activating mutation is present in >90% of PDAC — the earliest driver. Subsequent losses: CDKN2A (p16), TP53, SMAD4/DPC4. PDAC marker = CA 19-9. Classic signs: painless jaundice, Courvoisier sign (palpable non-tender gallbladder), Trousseau sign (migratory thrombophlebitis).

Histology: Liver, Gallbladder & Pancreas — Active Recall