Mandatory Review (does not include all material involved in picture only slides)

Pharynx

- Nasopharynx → pseudostratified columnar epithelial // cilia & mucus

- Oropharynx → non-keratinized stratified squamous epithelial
Posterior cervical triangles:
- Occipital – sensory cerv nerves, CNXI, brachial plexus trunks
- Omoclavicular – subclavian a./v., suprascapular a., supraclav nodes
Anterior cervical traingles:
- Submandibular – submandibular gland/nodes, facial a., CNXII
- Submental – small nodes, veins
- Carotid- carotid sheath, CNXI/XII, neck viscera, motor cervical nerves
- Muscular – neck strap muscles, neck viscera
McBurney point
- The point over the right side of the abdomen that is one-third of the distance from the anterior superior iliac spine to the
umbilicus
- Point roughly corresponds to the most common location of the base of the appendix where it is attached to the cecum
Anterolateral abdominal wall
- Rectus sheath – encloses rectus abdominis. epigastric a/v, lympathic vessel, T7-12 abdominal n.// b/w midline & midclav line
- Abdominal nerves – thoracoabdominal; anterior rami T7-11
- Arcuate line – occur 1/3 of distance from umbilicus to the pubic crest// horizontal line that demarcates the lower limit of
posterior layer of rectus sheath. Also, where inferior epigastric vessels perforate rectus abdominis
- Inferior epigastric vessels – branch of external iliac a.
- Superior epigastric vessels – from internal thoracic a.
Abdominal skeletal muscles (17)
- Somatic nervous system
o Somatic motor & somatic sensory carried on anterior rami of spinal n. from T7-11
o If skeletal muscle weakness of torso & lower limbs → must be prob including & below thoracic spinal nerve region
1. External abdominal oblique
2. Internal abdominal oblique
3. Transversus abdominis
4. Rectus abdominus
Actions =
o 1,2,3,4 → all compress and support abdominal viscera
o 1,2,4 → flex and rotate trunk
o 4→ stabilize and control pelvic tilt
Pancreas
- Posterior to the stomach
Vessels of posterior abdomen
- L renal vein (I think both renal v. honestly)→ artery lies posterior
Azygous system of veins
- Drain back and thoracoabdominal walls
- Azygous v. – collateral pthwy b/w SVC & IVC // runs on R side// drain into SVC
o IVC usu give rise to azygous v.
- Hemi-azygous v. – usu from L renal v., drain into azygous v.
Mediastinum
- lies with the thorax, posterior to sternum and anterior to vertebrae
- located between the lungs; enclosed on the right and left by pleurae
- it consists of four compartments
- major structures within the mediastinum: heart, esophagus, trachea, great blood vessels, thymus, phrenic/vagus nerves, thoracic duct
- anterior → posterior = thymus, veins, arteries, airway, alimentary tract, lymphatic trunks
Superior mediastinum
- BORDERS→ Superior: first rib, inferior: sternal angle (T4,5), anterior: manubrium of sternum, posterior: T1-4 vert, lateral:
mediastinal pleura
- Contents → esophagus, trachea (until sternal angle), arch of aorta, branches of arch, brachiocephalic v., SVC upper half, phrenic,
vagus n., azygous v./arch, thymus, thoracic duct, & recurrent laryngeal n.
o Esophagus → enter superior mediastinum b/w trachea and vertebral column, lie anterior to T1-4, compressed
anteriorly by root of left lung, thoracic duct usu lie on left side of esophagus // descends & passes through diaphragm at
esophageal hiatus // lies in more than one mediastinal compartment bc of vertical passing (superior to posterior
mediastinum)
o Trachea → enter superior mediastinum just right of medial plane
Diaphragm openings
- The caval opening lies at the level of the T8 vertebra in the central tendon.
o IVC & branches of the right phrenic nerve.
- The esophageal hiatus/opening lies at the level of the T10 vertebra in a sling of muscle fibers derived from the right crus at the left of
median plane.
o Esophagus, the right and left vagus nerves, the esophageal branches of the left gastric vessels & the lymph vessels.
- The aortic hiatus/ opening lies anterior to the body of the T12 vertebra between the crura.
o Aorta, thoracic duct & azygos vein.
Posterior Mediastinum
- BORDERS→ superior: sternal angle (T4,5), inferior: diaphragm (T12), anterior: posterior aspect of pericardium, posterior: T5-
T12 vertebrae, lateral: mediastinal pleura
- Contents → right vagus plexus (also superior media.), azygous v., esophagus, Lvagus plexus (also sup. Media.), descending aorta
(thoracic), & hemi-azygous v.
Lymphatic system
1. return of interstitial fluid to the circulation system (blood volume)
2. immune protection
o primary lymphatic organs
o secondary lymphatic structures
3. transport of dietary fats
- Return of overflow:
o Fluid in vessels: lymph
o Interstitial fluid travels into open lymphatic capillaries (open circulation)
o Lymph fluid in lymphatic vessels passes lymph nodes for immune surveillance before traveling into subclavian veins
o Afferent → LN→ efferent → trunk → ducts → subclav v.
o Travels towards the heart
- Lymphatic Trunks (Collecting Vessels)
o Jugular (paired) = drains head & neck
o Subclavian (paired) = drains upper limb
o Bronchomediastinal (paired)
o Lumbar (paired)
o Intestinal trunk (unpaired) = into cisterna chyli (dilated sac @ L1-L2)
▪ (lumbar trunk also drains into cisterna chyli)
Lymphatic Ducts
- Right lymphatic duct = receives lymph from R. subclavian trunk & R. jugular trunk and right bronchomediastinal
- Thoracic duct (left lymphatic duct) = starts at T12, roughly runs posterior to esophagus before moving left at T5; root of neck, lateral
towards left subclavian vein, cisterna chyli into thoracic duct
→ Both drain into subclavian veins (venous angle)
Spleen
- Secondary lymphoid organ
- Soft, purple organ with dense irregular CT capsule
- Immune cells supported by reticular fibers/network
- Located in LUQ or left hypochondriac region of the abdominal cavity
- Rich blood supply
- Dilated discontinuous capillaries called sinusoids which allow RBCs ro be filtered
- Functions =
o Filter blood & initiate immune response from antigens in white pulp
o Phagocytizes damaged/old RBC in the red pulp
o Hematopoiesis (fetus)
- Red pulp
o Sinusoids (leaky capillaries by design)
o Macrophages
o RBC slow down & old RNC destroyed by macrophages
- White pulp
o Location of B-cells, Tcells, & macrophages
o Promotes adaptive immunity when systemic pathogens
CNX (vagus n)
- parasympathetic (visceral) sensory to & autonomic motor from smooth muscle of vessels, respiratory, GI & GU/repro
- special sense for taste from epiglottis & palate
- branches of the vagus nerve supply somatic motor to skeletal muscles for speech & somatic sensory from some of the external ear
- At the base of the neck, the right and left nerves have differing pathways:
o The right vagus nerve passes anterior to the subclavian artery and posterior to the sternoclavicular (SC) joint, entering the
thorax.
▪ Posterior vagal trunk
o The left vagus nerve passes inferiorly between the left common carotid and left subclavian arteries, posterior to the
sternoclavicular joint, entering the thorax.
▪ Anterior vagal trunk
- create esophageal plexus, cardiac plexus, pulmonary plexus
- Enter abdomen: terminates by dividing into branches that supply the esophagus, stomach, SI & LI
- Cervical division
o Exit cranium and enter neck through jugular foramen, R/L vagus n enter carotid sheath & cont to root of neck
o Branches – superior laryngeal n (mixed), internal (snsory)/ external (motor) branches, & right recurrent laryngeal (mixed)
- Thoracic division
o Vagi enter thorax though superior thoracic aperture
o L vagus contribute to anterior esophageal plexus // R vagus contribute to posterior esophageal plexus
o Branches – L recurrent laryngeal n. (mixed): all distal branches convey PNS & visceral afferent fibers for reflex stimuli,
thoracic cardiac branches, pulmonary branches, esophageal plexus
o
Phrenic n.
 - R. phrenic, anterior to anterior scalene muscle (anterior to r subclav a.), posterior to R. subclav v. & SVC
Splanchnic nerves
- Sympathetic to abdomen
Autonomic nervous system
- Receptors located smooth muscle (tunica media) of arterioles: not all blood vessels have all receptors
o activated β2 receptors: lead to arterial vasodilation (decrease TPR)
▪ weak binding by NE, strong binding by EPI
▪ located on arterioles of skeletal muscle & coronary arteriole blood supply
o activated ⍺1 receptors (preferred) and ⍺2 receptors: lead to arterial vasoconstriction
▪ located on arterioles of most peripheral arterial & venous blood supply locations
▪ ⍺1 receptors promote strong vasoconstriction on arterial blood supply (increase TPR)
▪ less potent in arterioles to myocardium & brain
▪ large role in regulation of blood pressure by promoting arteriole vasoconstriction and venous capacitance
o activated muscarinic receptors (M2 & M3); lead to arterial vasodilation
▪ M3 coupled to formation of NO
BMS 8.1 The student will locate, describe the boundaries, and establish the significance of each of the following topographical
structures/spaces of the abdomen
** the GI tract is a continuous tube that extends from mouth to anus**
Alimentary canal
- Oral cavity to oropharynx → esophagus → stomach → small intestine (duodenum, jejunum, ileum) → large
intestine (cecum, descending/ascending/transverse colon, rectum (storage)) → anus (exit only)
Sphincters
- Bands of smooth muscle (* except *)
o Upper esophageal sphincter → proximal pharynx into esophagus
▪ Comprises striated muscle (Inferior pharyngeal constrictor) yet is not under conscious
control
▪ Opening of the UES is triggered by the swallow reflex
o Lower esophageal sphincter: distal esophagus into cardia of the stomach
▪ Cardia (part of stomach attached to the esophagus) overlaps w/ but does not contain the
lower esophageal sphincter (LES) (= cardiac sphincter, gastroesophageal sphincter,
inferior esophageal sphincter)
o Pyloric sphincter: pylorus of stomach into proximal duodenum
o Ileocecal sphincter: ileum into cecum/proximal ascending colon
o No colon sphincters → smooth muscle bands form haustra (sac like segments)
o Anal sphincters → internal anal sphincter & *external anal sphincter* (skeletal muscle) – most time
overrides internal anal sphincter
Mouth
- Mechanical: teeth (omnivore dentition) chewing
- Chemical:
o Salivary amylase for sugars
o Lipase for TGs
o Mucus/lubrication (bolus) for swallowing
o Oral hygiene (decrease bacterial build up/ washes mouth)
o Antimicrobial action
sec
4rate see
- Food & saliva forms a bolus which is swallowed
o Tongue helps to mix together
o Solubilize dry food

PNS Irate
o All processes are automatic from this point forward
- Autonomic control
o PNS stimulation to inc rate of secretion

RUQ
o SNS stimulation to mostly dec rate of secretion
o GI hormones
Four abdominal quadrants
- Used in physical exam & helps localize clinical systems
gus LUQ
-
-
RUQ, LUQ, RLQ, LLQ
Transumbilical line/plane reflux reflux
o Horizontal or transverse plane
o
o
Creates upper from lower quadrants
Passes through umbilicus pancreatitis relations
o b/w L3-L4 vertebrae
1. RUQ

2.
o
LUQ
Gastric reflux, gallbladder dz, hepatitis, kidney stones in hernia appendicitis
o Gastric reflux, pancreatitis, AD, kidney stones in herni

E
3. RLQ AFvertiano
o Appendicitis, inguinal hernia, kidney stones, ovarian cysts, ovarian torsion, testicular torsion
4. LLQ
o Inguinal hernia, diverticulitis, kidney stones, AAA, ovarian cysts, ovarian torsion, testicular torsion
9 abdominal regions
 - delineated by four planes: two sagittal planes (midclavicular planes to midinguinal points) & two transverse planes (subcostal planes
passing through the inferior border of costal cartilage)
o umbilical region → middle region named for umbilicus (navel) that lies in its center
o epigastric region → superior to umbilical region
o hypogastric/pubic region → inferior to the umbilical region
o R/L hypochondriac → inferior to costal cartilages and lateral to epigastric region
o R/L lumber (flank) → lateral to umbilical region
o R/L iliac (inguinal) → lateral to the hypogastric region
- Two vertical planes → R/L midclavicular line: midpoint of clavicle to midpoint of inguinal ligament
- Two horizontal planes:
o Subcostal plane (tenth costal cartilage on either side L3 vertebral bone) *** preferred over transpyloric plane***
▪ Horizontal plane
▪ Transverses the body at 10th costal space, cuts body of third lumbar vertebrae
o Transtubercular/intertubercular plane (tubercles of iliac crest on either side and the body of L5 vertebral bone)
▪ Passes through iliac tubercles
▪ Its plane cuts the body of 5th lumbar vertebra
- Transpyloric plane (Addison’s)
o Located ½ way b/w jugular notch and upper border of pubic symphysis
o Roughly hands breadth beneath xiphoid process of human sternum
o MC cuts though the pylorus of stomach
o Tips of 9th costal cartilages & lower border of first lumbar vertebra (L1)
Esophagus
- Enters superior mediastinum b/w trachea & vertebral column (right of thoracic duct)
- At tracheal bifurcation, esophagus enter posterior mediastinum
- Passes through the esophageal hiatus in the diaphragm
- 1/3 skeletal muscle (conscious control), 1/3 mixed, 1/3 smooth muscle (unconscious)
- Consists of two anatomically & physiologically distinct regions:
o Proximal striated muscle → cervical esophagus (conscious)
o Distal smooth muscle portion → inferior thoracoesophagus & abdominal esophagus
(unconscious)
- Based on type of innervation affected, they can be broadly classified into d/o:
o Inhibitory innervation – decrease inhibitory leads to diffuse esophageal spasm or achalasia
o Excitatory innervation
- Esophagus is for WEAR & TEAR → un-keratinized stratified squamous epithelium beginning to end
o b/w esophagus & rectum → secretion + absorption → simple columnar epithelium
- Layers → lumen, mucosa, submucosa, muscularis externa, adventitia
BMS 8.6 The student will locate the anatomic positions and describe the functional anatomy (histology) of the liver, gallbladder,
pancreas, spleen, kidneys, ureters, adrenals, stomach, duodenum, jejunum, and ileum of the small intestine, cecum, appendix, ascending,
transverse, descending and sigmoid aspects of the colon, and the rectum and the sphincters (valves).
Accessory GI organs
- Feed into tract
- Ability of GI tract to digest nutrients rests on the sequential exposure of the meal to a series of secretions.
- The first secretion encountered when food is ingested is saliva
- Saliva is produced by three pairs of salivary glands
o Three exocrine salivary glands have ducts the empty into the oral cavity → parotid, sublingual & submandibular
- Pancreas = exocrine
Salivary glands
- PNS carried on cranial nerves to salivary glands
- CNIX → parotid gland
- CNVII → submandibular & sublingual gland
- Smell, taste, sound, sight → higher centers → salivatory nucleus of medulla  sleep, fatigue, fear, pressure in mouth
o Parasympathetics → otic ganglion – ACh → parotid gland
→ submandibular ganglion f– ACh → submandibular gland
RESULT → inc salivary secretion via effects on acinar secretion & vasodilation
Greater Omentum
- Layers of peritoneal folds, ribbons of adipose tissue for cushioning
- Also prevents visceral peritoneum of intestines from sticking to parietal peritoneum lining
in abdominal wall
- Hangs off greater curvature of the stomach to transverse colon, hang like apron over
intestines
Lesser omentum
- Attached to lesser curvature of stomach to proximal duodenum to the liver
BMS 8.7 The student will explain the smooth muscle contraction physiology as it relates to
peristalsis in the GI tract.
Digestive process (6 fn of GI tract)
1. Ingestion: taking food into digestive system via mouth (IV glucose NOT ingested)
2. Secretion: 7L of product released into GI lumen per day
3. Mixing/propulsion: moving food through digestive tract, includes swallowing & peristalsis
o Swallowing – voluntary
 o Peristalsis – around constriction, involuntary, major means of propulsion by waves of contraction & relaxation of GI
tube, mixes and moves food (PNS)
4. Digestion: mechanical and chemical (mostly PNS)
o Mechanical – physical preparation of food for digestion, chewing (mouth), churning (stomach), segmentation (intestines)
o Chemical – catabolic steps where complex foods are chemically broken down into smaller molecules via activity of acid
and enzymes in GIT
5. Absorption
o Passage of digested particles into blood (monosacc, a.a nucleic acids) or lymph (fats) (FOR FIRST TIME)
o Small intestine = major site
6. Defecation
o Elimination of undigestible substances
BMS 8.8 The student will specify the cell type, anatomical location & function of the endocrine cells secreting gastrin, secretin, CCK,
somatostatin and Ghrelin
Control of Gut blood flow
- Blood flow proportional to local activity – meal = inc blood flow (2-3x) for 3-6 hrs
- Causes of activity induced blood flow
o Vasodilator hormones = gastrin, secretin, CCK
o Low oxygen (high adenosine)
- Nervous control of blood flow
o PNS = inc gut activity = inc blood flow
o SNS = directly dec blood flow, autoreg: escape, exercise, shock
ANS – smooth muscle innervation
- SNS
o Alpha-2 adrenergic receptors → causes GI sphincter smooth muscle contraction
o Alpha-1 adrenergic receptors → less important
o Beta-2 adrenergic receptors → causes GI tract smooth muscle relaxation
- PNS
o M1 cholinergic receptor → causes stomach & intestine smooth muscle contraction (inc GI motility): propulsion
o M3 cholinergic receptor → glandular cell activation (increase GI secretion)
Stomach (108-9)
- Food is stored in the stomach; mixed with acid, mucus, and pepsin & released at a controlled, steady rate into the duodenum
- Functions:
1. Storage: acts as a temporary reservoir for food
2. Secretion of hormones: gastrin & ghrelin
3. Secretion of H+ to kill microorganisms and activate pepsinogen
4. Secretion of intrinsic factor to absorb vitamin B12 (cobalamin)
5. Secretion of mucus and HCO3 to protect the gastric mucosa
6. Secretion of water for lubrication and to provide aqueous suspension of nutrients
7. Motor activity for mixing secretions (H+ and pepsin) with ingested food
8. Coordinated motor activity to regulate emptying into duodenum
Hunger hormone
- Stimulation of growth hormone secretion → ghrelin binds growth hormone secretagogue receptor (GHSR1a) in the anterior
pituitary resulting in the secretion of growth hormone
- Increase hunger → hypothalamic appetite regulation receptors
o Additionally, humans injected w/ ghrelin reported sensations of intense hunger
o Hippocampal receptors & regions known to be involved in reward systems
o Ghrelin appears to activate some of the same circuits that are involved in drug reward
- Ghrelin also appears to suppress fat utilization in adipose tissue
o Ghrelin is synthesized as a preprohormone, then proteolytically processed to yield a 28-amino acid peptide
- Stomach empty = inc ghrelin = inc appetite
- Stomach full = dec ghrelin = dec appetite
Ghrelin

gastric ans ghrelin

- Produced mainly by gastric cells of stomach
- Produced by cells of pancreas & adrenals
- Stimulates food intake (appetite regulation)
- Promote body weight gain
- Promote adipogenesis
- Levels increase before meals & decrease after meals
Leptin (def cause fat mouse)
- Produced by adipose tissue
-
-
Bind to neuropeptide neurons of hypothalamus, decreasing their activity
Signals brain that the body has had enough food to eat (satiety)
adipose tissue leptin
- Levels increase after meals
- Inhibits ghrelin secretion & suppresses ghrelin receptors
BMS 8.11 The student will identify and describe the vascular components of the abdomen including the course and major branches of the
abdominal aorta, the major arterial blood supply to each organ, various regions of the small intestines, cecum and colon, and the
anatomic organization and purpose of the portal venous system.
Abdominal Aorta (110-12)
- Celiac trunk branches → common hepatic a., left gastric a, splenic a.

3
celiac splenia
 domain
fine
a
o Celiac trunk supplies systemic blood to: esophagus entering stomach, stomach, proximal duodenum (1 st, 2nd parts), liver,
gallbladder, spleen & pancreas
- Common hepatic a. has two branches → proper hepatic a. (give rise to R/L hepatic a) & gastroduodenal a (R gastro-omental a. from
this)
o L gastro-omental a. from splenic a.
o Proper hepatic a. give rise to R. gastric a.
- Gastro-omental a. blood supply to greater omentum
BMS 8.20 The student will describe the overall role of the gastrointestinal system with respect to the whole-body balance of water,
electrolytes, carbohydrates, fats, and proteins including the processes of digestion, absorption, metabolic production, metabolic
consumption, secretion and excretion, especially their role in vomiting and diarrhea.
POLYMERS MONOMERS
1. Polysaccharides → disaccharides → monosaccharides
o Glycogen → sucrose → glucose & fructose
o Starch → maltose → glucose & glucose
Lactose → glucose & galactose
2. Lipids
o TG 3 f.a chains + glycerol
o Phospholipids 2 f.a chains, glycerol, & phosphate group
o Steroids 4 carbon rings (lipid but not lipid sol, hard to dissolve)
3. Proteins→ peptides → a.a: amino group, carboxyl group off central carbon, & side chain (NOT STORED, eat)
4. Nucleic acids nucleotides: 5C sugar, phosphate, & nitrogen base
Digestion of Carbohydrates (polysacc) → monosaccharides
1. Polysaccharides → disaccharides → monosaccharides
- Glycogen (amylase) → sucrose (Sucrase) →glucose & fructose
- Starch (amylase) → maltose (maltase) →glucose & glucose
Lactose (lactase) →glucose & galactose
- Final products of carbohydrate digestion are all monosaccharides, mostly glucose
- 80% glucose & 10% each of fructose and galactose
Absorption of Carbohydrates
- Absorption is RATE LIMITING STEP in carbohydrate assimilation (= digestion & absorption)
- Glucose & galactose need 2ndary active transport
o Compete for membrane carrier via SGLUT-1
o Energy from NAK ATPase
- Fructose needs facilitated diffusion via GLUT-5
o No energy req
o Req concentration gradient
Digestive enzyme production
POLYMERS DISACC MONOMERS
Salivary glands Pancreas Intestinal Mucosa
- Alpha Amylase - amylase -enterokinase
- Lingual lipase - trypsin -sucrase
Stomach - chymotrypsin -maltase
- Pepsin -carboxypeptidase -lactase
-elastase -trehalase
-lipase-colipase -alpha-dextrinase (isomaltase)
-phospholipase A2 -amino-oligopeptidase
-cholesterol esterase -dipeptidase
Ex) ^ protein→ peptide ^peptide → a.a
- Purple = carbs
- Green = proteins
- Yellow = TGs
Six main types of nutrients
- Primary fn of GI tract = serve as portal whereby nutrient and water can be absorbed into the body
- Examples of what is absorbed → water, carbs, lipids, proteins, minerals (inorganic), vitamins (organic substances req in small amnts
for normal metab→ fat sol = KADE, water sol = Bs & C)
- Essential nutrients cannot be made in sufficient amnts by body
Absorption- splanchnic circ
- Splanchnic () circulation (inward →GI tract)
- Circulation of gastric, small intestine, colon, pancreas, & spleen
- Arranged parallel with one another
- Extensive anastomose
- Three major arteries → celiac trunk, superior mesenteric a., inferior mesenteric a.
Sites of absorption
- Stomach → absorbs ethanol, NSAIDs, ASA
- Duodenum & jejunum → absorbs nutrients, vitamins, various ions, water & electrolytes
- Ileum → bile salts & vitamin B12 (of major clinical significance)
- Colon → absorbs extra water & electrolytes
- Rectum → absorbs drugs such as steroids & salicylates
Minerals
 - Inorganic elements constitute (4% of body mass)
- Regulate enzymatic reactions
- Serve as co-factors
o Non-protein molecules that help enzyme’s function/lower activation energy
o Can be either inorganic ions (like metal ions like iron, zinc, magnesium) or organic compounds
Vitamins
- Organic molecules req in small amnts (are essential = cannot be synthesized by humans & need to be ingested in the diet to maintain
health and prevent disease)
- Most function as CO-ENZYMES
o A specific type of cofactor that is an organic molecule (subset of co-factors)
o Coenzymes are specifically organic molecules, often derived from vitamins
o Often act as intermediate carrier of chemical groups or electrons during enzymatic rxns
- Provitamins – converted into a vitamin within the body
- DO NOT PROVIDE ENERGY → water sol vitamins NEEDED for energy RELEASE
- Antioxidant vitamins: C, E, & beta carotene (converts to A)
- Types
o Water sol: dissolve in water, needed for energy release, & too many water sol vitamins = excreted in urine
o Fat sol: dissolve in fat, remain in the body for periods of time, KADE, & too many can lead to toxic build up stored in
fatty tissues, liver & kidneys
1. Vitamin B1 = thiamine
o Water soluble → excreted in urine, half-life 10-20d
brown o Found in yeast, brown rice, legumes, whole grain cereals & pork
▪ Low in milk, fruits, veggies, white rice, or milled white cereals
yeast grains o Absorbed in small intestine → bound to albumin & transported to liver
▪ Highest concentration in skeletal muscles liver heart kidneys and brain

rice
leanmes
o Vitamin co-enzyme for initiation of nerve impulse propagation (no memories), carb metabolism, & branched chain
a.a metabolism
▪ BCAA essentials (leucine, valine, isoleucine) = inc muscle growth
▪ BCAAs found in eggs, dairy, meat & powder dietary supps
o Deficiency result in →
▪ Beriberi = infantile & adults have neuro sx
▪ Wernicke-korsakoff syndrome = lead to peripheral neuropathy → alcohol excess can lead to thiamine def
2. Vitamin B2 = riboflavin
o Water soluble → excreted in urine

fish
o Found in milk eggs meats fish green veggies yeast and enriched foods (fortified cereals and breads)

milk o
o
Absorbed in proximal small intestine → bound to riboflavin transport & transported to the liver & can cross BBB
Co-enzyme for energy producing respiratory pthwy/cellular respiration metabolic pthwys
▪ FAD (ETC) & synthesis of hemoglobin proximal
mythover o Riboflavin def (pure def is RARE)
▪ Usu acc by mult water soluble vitamin def such as anorexia nervosa, malabsorptive syndromes (celiacs, small
3. Vitamin B3 = niacin
malignancies)
intestine
o Water soluble → excreted in urine
o Found in yeast, meats (esp liver), salmon, beef, tuna, grains, legumes, corn treated with alkali (corn torilla), bran
and seeds
o Absorbed in small intestine → transported to & taken up by liver, kidneys & erythrocytes
o Coenzyme for:
▪ synthesis & metab of carbs, protein, & FA metab (energy and fat metab)
▪ energy producing respiratory pthwys → NAD (ETC)
o Niacin def
▪ Pellagra (raw skin) → 3Ds = dermatitis, diarrhea, and dementia
o Toxicity = flushing reaction (causes small capillaries in skin to dilate
o May be useful in Raynauds
4. Vitamin B9 = folate
o Water soluble → excreted in urine

afolate mash
▪ Folate considered in conjunction w/ B12

3
▪ High folate can MASK B12 def

atp gE
o Found in asparagus, brussels, leafy greens, beans, sunflower seeds, liver, & seafood

Bin DEF
▪ Folic acid = synthetic form
o Absorbed in small intestine → transported to the liver, kidneys, & erythrocytes
o Coenzyme for neuro function & hemtopoiesis
o Folate def = result from excess alcohol → macrocytic anemia (MCV > 100fl)
5. Vitamin B12 = cobalamin
o Water soluble → excreted in urine, some can be stored in liver
o Found in ANIMAL products → meat, poultry, fish, eggs, dairy
o
o
Absorption in ileum and REQ intrinsic factor
REQ for nucleic acid metabolic processes → growth and nerve fn B12 ileum 1Frea
o Cobalamin def → vegans typically largest at risk group

Mistress ▪
▪
Macrocytic anemia (MCV > 100fl)
Pernicious anemia
 6. Vitamin C = ascorbic acid
o Water-soluble → excreted in the urine
o Found in citrus fruits, strawberries, broccoli, brussels, & white potatoes
o Absorbed in distal small intestine

stamens o
o
Necessary for collagen synthesis, neurotransmitter synthesis, FA transport & an antioxidant
Ascorbic acid def
▪ Scurvy = bleeding gums and poor wound healing
[Link]
youth
▪ major cause of morbidity/death in Europe during great potato famine, US civil war, exploration of north pole &

▪
California gold rush
Can occur in drug or alcohol abusers
intestine
o Toxicity = bloating, inc risk of kidney stones, diarrhea
7. Vitamin A (Queen Meri’s fav vitamin)
o Lipid soluble→stored in liver
o Provitamin A carotenoids (beta carotene & others) are converted by body into Vitamin A
o Found only in animal products – liver kidney egg yolks and butter
o Absorbed in small intestine

iini
o Carotenes are a plant source of provitamin A → green leafy veggies and carrots (carotene palms like MERI)
▪ Conversion to vit A occurs in walls of the intestine, liver, and kidney
o Needed for visual pigments, epithelial cell growth/maintenance & reproduction
o Def = RARE in US
▪ Pop at risk are pt w/ d/o of fat malabsorption (pancreatic insuff, celiac, crohns, short bowel syndrome, s/p
bariatric sx), pt w/ liver dz, alcoholics, & those on fat free diets
o Toxicity = remember lipid sol can be store in adipose tissue so can accumulate over time
8. Vitamin D = calciferol
o Lipid soluble → stored in liver
▪ Req bile to be absorbed for storage in liver
▪ Liver & kidney needed to yield active vit D
▪ UV light converts 7-dehydrocholesterol → D3
▪ Still need enzymes to be converted correctly

metformin o

o
Found in animal fat/fat products → cheese, butter, fish, (very few foods naturally contain vit D, except fatty fish livers
do)
Absorbed in small intestine
o Essential for Ca & Phosphate balance (bone metab)
o Def leads to rickets (children) & osteomalacia (adults)
▪ Imperfect calcification
▪ Softening/distortion of bones, esp weight bearing long bones
o Production
▪ Vit D → enzymes in liver → 25-hydroxyvitamin D (major circ form)
▪ Kidney → 1,25 dihydroxyvitamin D (active form of vit D)
▪ serum level of 1,25 dihydroxyvit D have little-no relationship to vit D
stores
• reg primarily by PTH levels which in turn reg by Ca or vit
D
▪ Vit D levels = 25 hydroxyvitamin D concentration
• Vitamin D sufficiency, insufficiency, or deficiency (rickets,

o Rickets (vit D def)

osteomalacia)

K D
E

bilgtncgh [Link]
▪ Hypocalcaemic rickets is MC
▪ A group of disorders in which intestinal aborspotion of calcium is insufficient to match the Ca requirements for
bone growth
▪ Bow legged
9. Vitamin E = tocopherol
o Lipid soluble → stored in liver, req pancreatic and biliary fn
o Vit E is found in variety of foods including almonds, vegetable oils, and cereals
o Protects cell membranes from oxidation and destruction
o Vit E (as alpha-tocopherol) works as free radical scavenger, protecting polyunsaturated FA, major structural
component of cell membranes from peroxidation
o In adults and children, vitamin E def is uncommon BUT can cause neuromuscular d/o & hemolysis
o Toxicity = can cause major bleeding events, these can be serious including the potential for intracranial hemmorrhage
10. Vitamin K
o Lipid sol → stored in liver, requires pancreatic & biliary functions, absorbed in small intestine

siren
o in many foods = spinach (other leafy greens), cabbage, cauliflower, veggies and cereals
o Most obtained from that formed by intestinal bacteria → requires bile salts
o Necessary for formation of prothrombin, major role in coag pthwy → PT/INR prolonged with deficiency
o DEF= inability to form clots, easy bruising
Lactose
- Is a disaccharide
- Broken down into glucose + galactose by lactase
- Lactase enzyme located → enterocyte brush border enzyme
 -
maritima arm

As an adult → little of the enzyme is made at the brush border/microvilli of small intestine enterocytes /epithelial cells; enzyme
lactase needed for digestion of polysaccharides from mammalian milk
- Normal to down-regulate receptors for these as we get older
- NOT absorbed by the small bowel passes rapidly into the colon
- Some exceptions: humans exhibit unusual persistence of lactase throughout adulthood, northern European genetics, or other dairying
cultures

HDV LDU
Dietary sources of cholesterol
1. Saturated f.a
o Animal fats & tropical fats - butter, coconut oil, palm oil, whole milk, cheese, ice cream, coconut milk, coconuts, red
meat, egg yolks, chicken skin

uncut mono coconut peanut

→ RAISE LDL & HDL
2. Unsaturated f.a
- Monosat= canola oil, olive oil, peanut oil, nuts, avocados, olives
- Polysat= cottonseed oil, cottonseed oil, fish, corn, soybean
Pym sat wormseed com
→ both LOWER LDL & RAISE HDL (both forms unsaturated) (best is mono)

-
3. Trans f.a MHD
Margarines, vegetable shortening, deep fried chips, fast foods, commercial baked goods, partially hydrogenated vegetable oil
→ RAISE LDL (worst)
Statins (HMG-CoA inhibitors)
-
an
Reduce cholesterol production in the liver & increase ability of the liver to remove LDL from the blood
- Generally, target LDL but can help with TGs
Lipid macromolecules
- TGs = 3 FA chains + glycerol backbone

1
- 90% of dietary lipid
- Phospholipids = 2 FA chains + glycerol + phosphate group
- Steroids = 4 carbon rings
- Sphingolipids, fatty acids, & fat-soluble vitamins
Lipid transport: chylomicrons
- Resynthesized TGs
remnants
-
-
Degraded to remnant by the action of lipoprotein lipase (LpL)
Remnants are taken up by liver cells
Chylonitrons apt
Staff protein
- FA of 10-12 carbons = unmodified transported into portal blood
- FA >12 carbons = resynthesized into TG in enterocyte
Chyle micron
-
-
-
Coated with a layer of protein→ chylomicron
Enter LYMPHATICS (via lacteal)
Chylomicrons are NOT the same as micelles (micelles have added bile salt)
coated
Chylomicron Life cycle
- Formed in intestinal enterocyte & packaged by Golgi apparatus → secreted by exocytosis into interstitial space → enter central
lacteal of intestinal villi & transported via thoracic duct→ lipoprotein lipase (on capillary EC) works w/ apolipoprotein C to degrade
TG into FFA+glycerol w/in chylomicron → FFA + glycerol respired by cells or resynthesized to TGs for storage ORRRR chylomicron
remnant is phagocytized in hepatocytes
Lipoproteins: remnants of chylomicrons
- Chylomicron remnants → larger and heavier (MOSTLY TG) → VLDL
- Chylomicrons → largest and heaviest
- Higher % of lipid in lipoproteins = LOWER the density
- From largest/lightest to smallest/heaviest
1. Chylomicrons
▪ Transport dietary lipids absorbed in small intestines to liver
▪ FFA transported by LYMPH toward blood

B 48
▪ Mainly transport TGs
▪ In liver, release TGs → VLDL
▪ apoB-48 structural protein, also has apoA & apoC (I,II,II), and apoE
▪ apoB-48 lack LDL receptor binding domain → contribute to atherosclerosis
2. Very low-density lipoproteins (VLDL)→ atherogenic
▪ Transport triglycerides from liver cells (hepatocytes) to adipose tissue
▪ Remove enough TG = converted to LDL

B 100
▪ apoB-100 structural protein, also has apoC (I,II,II)
▪ b/c of apoB-100 → can bind to LDL receptor (still bad → atherogenic)
3. Low density lipoproteins (LDL)→ atherogenic
▪ Transport most cholesterol to cells
▪ Deposit cholesterol to smooth muscle of arteries (harder to breakdown)
▪ Product of VLDL catabolism
▪ Transport >60% cholesterol to cells & some TGs
• use receptor mediated endocytosis
• apoB-100 structural protein
• triggered by apoB-100 LDL receptor intrxn → receptor is recycled
• cholesterol intake down regs LDL receptor synthesis
• mutations of LDL receptors → inc plasma LDL levels → accel. Atherosclerosis
 ▪ LDL cholesterol when oxidized lead to → atheroma formation
▪ Deposit cholesterol to smooth muscle and arteries
4. High density lipoproteins (HDL)
▪ Transport cholesterol from body cells to LIVER for elimination
▪ Secreted by liver & small intestine
▪ Vehicle for transport of cholesterol from peripheral tissue to the liver (reverse cholesterol transport)
▪ LCAT enzymes in plasma req for HDL maturation → reduction of LCAT = dysfn of HDL
▪ Transport mainly esterified cholesterol from body cells → liver for elimination
▪ Able to REMOVE cholesterol from atheroma
▪ apoA-I structural protein, also apoA-II & apo-E (no contribute to atherosclerosis)

Saliva

I
- Ionic composition depends upon rate of secretion
- Composition (besides serous and mucus)
▪ Electrolytes: Na, Ca, Cl, K, HCO3
▪ Protective: immunoglobins, lysozymes, salivary peroxidase
▪ Other: urea, ammonia (nitrogen waste)
- Saliva is HYPOtonic
- Loss of saliva from body can lead to K depletion (aldosterone)
-
-
Serous fluid: watery secretion, contains alpha-amylase & lingual lipase (from mouth)
Mucus: contains mucin for lubrication hascapacith
mucus
- Thick secretion that is mainly water, electrolytes, and glycoproteins
- Mucus is essential for digestion b/c:
▪ Adherent (sticks to food & itself)
▪
▪
▪
Low resistance (lubrication)
Resistant to digestion
Has buffering capacity
buffer
- Salivary glands consist of blind end pieces (acini) that produce the primary secretion containing the organic constituents dissolved in a
fluid that is essentially identical in its composition to plasma
- Secrete 800-1500 ml/d of saliva
- Max rate of secretion → 4 ml/min
Histology of GI tract
- The intestine is composed if functional layers:
- Lumen: free space, in GI tract location of food & liquid substances
- Mucosa: (epithelial layer and opening), immediately adjacent to nutrients in the lumen is a single layer of epithelia cells;
MOST of Gi tract is lined by columnar epithelial cells
▪ Represents the barrier that nutrients must traverse to enter the body
▪ MOST superficial epithelial (superficial meaning inside the GI tract, so physically touching food)
▪ Vessels, lacteals, glandular cells
- Submucosa: (CT & blood supply) below the epithelium is a layer of loose CT known as the lamina propria & also some
smooth muscle
▪ Glands (duodenum), lymphoid nodules (ileum), nerve plexus
- Muscularis: muscle; typically, two concentric layers of smooth muscle, oriented circumferentially & then longitudinally
to the axis of the gut (circular & longitudinal muscle layers respectively)
▪ Mostly smooth muscle & nerve plexus
▪ Externa → inner circular & outer longitudinal layers (autonomic M1)
- Adventitia (CT) or Serosa (visceral peritoneum)
- Mesentery → support GI & blood supply (a/v, lymphatics, adipose)
Stomach → gastric mucosa
- Gastric mucosa contains many deep glands
- In cardia and pyloric region – glands secrete mucus
- In body of stomach + fundus – glands also contain parietal cells (acid, intrinsic factor) & chief cells (pepsinogen)
- Several glands open onto a common chamber → gastric pit → that opens in turn onto surface of mucosa
- Mucus + HCO3- secreted by mucus cells on surface of epithelium between glands
- Three cell types:
1. Mucous neck cells → mucus
2. Peptic cells (chief cells) → pepsinogen
3. Parietal cells → HCl and intrinsic factor (they produce HCl in response to below…)
- Gastric secretion (HCl) is stimulated by neural, paracrine and endocrine mechanisms:
▪ Histamine (via H2 receptors) – act by increasing intracellular cAMP
• HCl secretion
▪ ACh (M3 receptor) – inc intracellular Ca levels
• HCl secretion, mucus, pepsinogen, gastrin
▪ Gastrin (CCK2 receptors) – inc intracellular Ca levels
• HCl secretion (1500x more powerful than Histamine)
• Trophic activity
• Stimulate growth of mucosa of stomach, duodenal and colon

hormone
instomach
 • Surgical removal of stomach antrum causes atrophy of mucosa
• Pt w/ gastrin secreting tumor have mucosal hyperplasia & hypertrophy
- Both cAMP + Ca act via protein kinases to inc transport of acid into the stomach
- Somatostatin = inhibitor/stopper & decrease pH
Regulation of gastric secretion
- Vagal control
- Gastrin secretion not blocked by atropine
- Gastrin release peptide (GRP) – stimulates gastrin release from G-cell

-
-
- Somatostatin inhibits gastrin release from G-cell
Stomach acidification – pH <3 inhibits gastrin release
Small peptides and a.a. – directly stimulate gastrin release from G-cell
HU
Pepsinogen
-
-
-
Inactive secreted form of pepsin
HCl convert pepsinogen → pepsin
Pepsin converts more pepsinogen → pepsin
pepsinogen to pepsin
- Proteolytic enzyme, optimal pH (1.8-3.5), reversibly inactivated > pH 5, & irreversibly inactivated >pH 7-8
- Two signals stimulate secretion of pepsinogen → vagal stimulation (by ACh) & direct response to gastric acid pepsin
Intrinsic factor
- Stomach = dietary b12 bound by b12 binding proteins present in gastric juices
- Duodenum = pancreatic proteases digest binding proteins, releasing vitamin b12 which binds to intrinsic factor
-
-
In ileum = intrinsic factor + vitamin b12 complex absorbed
ONLY INDEISPENSABLE SUBSTANCE in gastric juice (we can’t replace it) ileum if Biz
Why doesn’t the stomach digest itself?
-
-
thick alkaline mucus
Rapid mitosis to replace dmg cells
absorbed
- Tight jn b/w cells to prevent acid leakage
- Trefoil factors are cytoprotective (TFF-3 or intestinal trefoil factor → help proteins fold in less susceptible way to acid)
- Only few fat soluble substances absorbed in stomach → alcohol, ASA, etc
BMS 8.21 The student will correlate the pathophysiology of commonly encountered GI diseases throughout the GI tract.
Gluten
- protein found in wheat barley and rye
- Gluten = Gliadin + Glutenin
o Gliadin = difficult for human digestive enzymes to break down
Gluten enteropathy
- Anything that dmg surface of small intestine, which alter nutrient absorption
- Celiac dz → gluten enteropathy results from hypersensitivity to gluten, a protein constituent of wheat barley and rye
- PATH→ gluten erroneously activates T-cell response (autoimmune) that dmg intestinal villi
o Malabsorption of iron, folic acid, & vit B12 → can lead to anemia
Gluten intolerance/sensitivity (non-celiac gluten sensitivity)
- Describes syndrome of sx responses to gluten ingestion in pt with NO serologic or histologic evidence of celiac dz
- Not autoimmune as in celiac dz & not IgE-mediated
- No tests or biomarkers
- Must r/o celiac dz, wheat allergy, or other possible causes of sx
o Adherence to gluten free diet is ONLY TX at this time
Sources of gluten
- Bread rolls, bagels, cakes, cereal, cookies, pasta/noodles, pastries/pies
- Possible → candy, communion wafers, drink mixes, gravy, imitation meat, seafood, sauce, soy sauce, seasonings, caramel
- GLUTEN FREE → grains and starches
o Amaranth, arrowroot, buckwheat, corn, flax, millet, montina, oats* (cross cotnam occasional*)
Nut allergies
- Several allergenic proteins
o Peanut, tree nuts, seed allergies some of MC food allergies in children & adults
o Nine major and minor allergenic proteins in peanut
- IgE mediated – Type 1 Hypersensitivity
o If systemic IgE:
▪ CV→ conduction dist
▪ Respiratory → sneezing, nasal congestion, laryngeal edema, wheezing, coughing
▪ GI tract → N/V/D, bloating, cramping
▪ Skin → flushing, pruritis
o If non-IgE mediated → atopic dermatitis
Metabolic disorders
- Impaired metabolism: both inborn errors or mutations
o Deficient or absent enzyme activity
o Changes in binding site of cofactor
o Precursors accumulated or impaired feedback inhibition
o Toxic metabolites produced as a result of the buildup or deficiency of needed end product
o 2ndary nutritional deficiencies
Lactose intolerance (lactase def or hypolactasia)
- Inability to digest & metabolize lactose (sugar found in milk)
- Lactose converted in COLON to short chain FA and hydrogen gas by the bacterial flora → sx of lactose intolerance
 lactose normally divested injejunum
- NOT AN ALLERGIC RXN b/c no immune response
took in wion mono
- Lactose (normally digested in the jejunum) passed along to the colon where Ecoli break it down into monosaccharides
o Disaccharides cannot be absorbed across wall of small intestine into blood stream, SO in absence of lactase, lactose
present in ingested dairy products remain UNCLEAVED and passes intact into colon
- E coli break down into monosaccharides producing large volumes of flatus
- Flatus distention of the colon causes pain
- E. coli breaks monosaccharides into FA which causes water movement into the colon = excess water in colon = diarrhea
Abnormalities of carbohydrate assimilation (= digestion + absorption)
- Lactose intolerance (acquired lactase def OR primary adult hypolactasia) → MC
o Genetically programmed to become lactose intolerant
o PATHO→ absence of brush border enzyme lactase of small intestine epithelial cells
o Lactose converted to short-chain FA

fructoseonly
- Lack of glucose/galactose carrier → RARE
Diagnosed at birth
SGLUT I
o
o Feed fructose
o Lacking SGLUT-1
Dysphagia
- Oropharyngeal = problems transferring the food bolus from the oropharynx to the upper esophagus
- Esophageal = impaired transport of the bolus through the body of the esophagus
- Difficulty swallowing, caused by either a pathological esophageal obstruction or an abnormal esophageal motility (functional d/o)
1. Pre-esophageal dysphagia
o Neurological disease (Parkinson’s, MS)
o Muscular disorder
o Autoimmune disorder (MG)
2. Esophageal motility d/o
o Spastic esophagus
▪ Diffuse esophageal spasm (or spastic DES) – in which contractions are uncoordinated
▪ Nutcracker spasms – in which contractions proceed in a coordinated manner, but the amplitude is excessive
▪ HTN LES – involve esophageal body & LES

VEHANEplexus
• Failure of normal relaxation of the LES assoc. w/ uncoordinated contractions of the thoracic
esophagus, resulting in functional obstruction and difficulty swallowing
• PATHO→ dysfunction of the ganglion cells of the myenteric plexus of the LES → relaxation

Msm o
o
LES
Ineffective esophageal motility
Achalasia 5
3. Obstructive dysphagia
o Stricture
- Esophageal dysphagia is almost always caused by disease in/or adjacent to the esophagus but occasionally the lesion is in the
pharynx or stomach
- in many of the pathological conditions causing dysphagia, the lumen becomes progressively narrowed and non-distensible
- Two plexuses = myenteric plexus and submucosal plexus
Achalasia
- Dilation/widening of esophagus, sphincter might not be working correctly, including LES not relaxing
- PATHO→ unclear but several factors can lead to inflammation, fibrosis, & ganglion cell dysfunction within the myenteric plexus
o Genetics, autoimmunity &/or autoantibodies, and viral infection
Esophageal stricture
- Narrowing of the esophageal lumen which interrupts normal passage from the esophagus to the stomach
o MC to affect passage of food but liquid may still be able to pass
- 3 categories:
o Intrinsic – GED that narrow the lumen through inflammation, fibrosis, or neoplasia
▪ GERD can lead to intrinsic stricture (major RF)
o Extrinsic – dz that compromises esophageal lumen by direct invasion or lymph node enlargement
To o Peristalsis – dz that disrupt esophageal peristalsis &/or LES fn
Mallory Weiss syndrome (esophageal tear)
- Longitudinal mucosal lacerations in distal esophagus or proximal stomach
o MC where esophagus and stomach meet (GEJ or EGJ)
- Usu associated with forceful retching
- Laceration can lead to (severe) bleeding from submucosal arteries
GERD
- Aka acid reflux
- Chronic digestive dz that occurs when stomach acid or bile flows back into your esophagus
- Classified by esophageal mucosa →
o Erosive – with mucosal injury (GERD)
o Nonerosive – w/o mucosal injury (NERD)
- Spitting up blood is result is result of submucosal damage
- PATHO→
o Healthy pt → angle at which esophagus enters stomach (angle of His) creates a valve that px duodenal bile, enzymes, and
stomach acid from traveling back into the esophagus where they can cause burning and inflammation of sensitive
esophageal tissue
▪ Poor angle or closure of the LES
 o Other factors influence severity of GERD:
▪ Frequency of acid reflux
▪ pH & clearance rate of gastric mucus
▪ secretion rate & pH of gastric mucus to neutralize acid
▪ integrity of mucosal barriers
▪ spicy/acidic food quantity
- Complications:
o Esophageal stricture – gradual narrowing of the lumen of esophagus
▪ In GERD, inflammation response of acid reflux → scarring will occur w/ repeated inflammation, benign
▪ Schatzki’s ring → LE ring typically at junction w/ stomach, narrow the LE and make swallowing difficult
o Esophagitis
▪ Inflammation (eosinophilic)
▪ Inflammation can damage esophageal layers leading to fibrosis
▪ Can also be caused by medication, reflux, & infection
▪ Infection – typically in immunocompromised pts→ CMV, HSV, Candida
• Esophageal candidiasis → fungal infxn MC source of esophageal infxn
• CMV esophagitis → common in AIDS when CD4 is <50
o Barrett’s Esophagus
▪ Chronic acid in lower esophagus
▪ Mucosa epithelial change from stratified squamous of distal esophagus to metaplastic columnar of
stomach at the Squamocolumnar junction (SCJ) (Z-line)
• Move from protective function to secretion function
• Cellular changes can lead to neoplasm (esp adenocarcinoma)
o Esophageal varices
▪ PATH→ enlarged hepatic portal veins from the LE
▪ Varices are result of inc portal HTN
• Dilated vein from hepatic portal system form vascular sprouts that connect high-pressure portal
venous system w/ low pressure systemic veins to try & correct an increase in portal resistance &/or
increase in portal inflow
o Esophageal neoplasm
▪ Among MC cancers & causes of death worldwide
▪ 2 major types account for 90% of cancers
• SCC

SCC
o Epithelial dysplasia → carcinoma in situ → invasive carcinoma
Phftication •
o Most are located ABOVE tracheal bifurcation
Adenocarcinoma
o Not MC but rapidly increasing in incidence
o Distal esophageal mucosa undergoes intestinal metaplasia → genetic alterations

adenocarcinoma distal
▪
o
o
Location = distal esophagus/EGJ
BELOW tracheal bifurcation
Epithelial change from stratified squamous of esophagus to metaplastic columnar of stomach at the SCJ
• Move from protective to secretion function
• Cellular changes can lead to neoplasm (esp adenocarcinoma)
Esophageal neoplasms
- Malignant growth can also lead to esophageal stricture
o Aggressive & high mortality
- Primary esophageal cancer
o SCC
▪ Typically, assoc with tobacco and alcohol use
keratosis ▪
▪
MC in middle esophagus (above trachea bifurcation)
arise from squamous cell epithelial lining of mucosa through repeated precursor lesions/insult such as:
• achalasia (chronic food stasis/inflamm), chronic esophagitis, smoking/chewing tobacco, alcohol,
diet low in fruit & vegetable (low antioxidant levels), possible role in HPV, genetic link w/

maintain autosomal dominant palmoplantar keratoderma (hyperkeratosis, RHBDF2 on chromo 2 –

a
protein code for EGF receptor)
o Adenocarcinoma
▪ Assoc w/ GERD, Barretts, tobacco use
▪ MC in distal esophagus
▪ Defined as columnar metaplasia w/ pseudogoblet & epithelial cells that replaces the stratified squamous
epithelium
• Pseudogoblet cells make an acidic mucin
▪ Genetic factors → mutation of TP53 gene (p53 protein) & aneuploidy (abnormal # of chromo in cells)
moused Gastroparesis
- Delayed gastric emptying
- Conditions producing symptomatic motor dysfunction:
o Hypertrophic pyloric stenosis
gastro ▪
▪
Pyloric muscular hypertrophy & hyperplasia
Multifactorial in infants

empty o Acute gastritis

nonte
 ga
7pm
dong none
▪ Inflammatory changes in the gastric mucosa erosion
▪ May involve entire stomach or only a region
▪ Erosive = dmg to mucosal defenses
▪ Nonerosive = caused by H. pylori
o Chronic gastritis
▪ Inflammation of inner lining of the stomach and atrophy
Diseases of the parietal cells
- Peptic ulcers
o Result from over acidity in stomach or duodenum
dara o
o
Defect in gastric or duodenal mucosa that extend through muscularis mucosa into deeper layers of wall
MC from NSAIDs & H. Pylori
- Pernicious anemia
autoab
-
o
Achlorhydria
Autoab directed against parietal cells or intrinsic factor cause a reduction in vitamin b12 absorption

Autoimmune dz of parietal cells

autoimmune
o
o Damaged parietal cells are unable to produce the req amount of gastric (HCl) acid
o Lead to inc in gastric pH, impaired digestion of food and inc risk of gastroenteritis
Heliobacter pylori
- Gram – bacteria, curved bacillus, motile (flagella), & high affinity for human gastric mucosa
- Produces urease – may be protecting H. pylori from acid dmg from gastric juices
- Most prevalent chronic bacterial infection
- PATHO→ bacteria invade epithelial cell surface (of mucosa) & cause dmg → toxins & LPS dmg mucosal cells → NH3 produced by
urease activity dmg cells
o Pangastritis is MC = high salt & low vitamins C & E → chronic inflammation + H. Pylori → result in atrophy of stomach
+ glands → hyposecretion of stomach acid → inc risk of gastric cancer
o Antral-type gastritis is LC = in antrum of stomach → inflammation + h. pylori → inc gastrin production → ulceration →
duodenal metaplasia → h. pylori infxn worsens → inflammation worsens
Gastrinoma: Zollinger-Ellison Syndrome

waiter
- Gastrin secreting tumor (MEN-1)
- Non-beta cell tumor of pancreas (MC) or G-cell tumors in deuodenum (LC)
- Continually secretes gastrin into blood → excess gastric acid in stomach & duodenum → sores → peptic ulcers
- Hypergastrinemia causes hypersecretion of acid
o Increased parietal cell mass & constant stimulation of hyperplastic mucosa → dec bile salts & lipase activity →

MEI
diarrhea, steatorrhea, hypokalemia
- a
Low pH inactivates pancreatic lipase & causes bile salts to precipitate → steatorrhea
- Hypokalemia → loss of GI secretions in stool
Gastroduodenal d/o
- Pathogenesis of many disorders tied to Helicobacter pylori:
1. Acute Gastritis (up to 92%) (MC)
2. Chronic Gastritis
3. Gastric Ulceration (up to 58-100%)
4. Duodenal Ulceration (up to 88-100%)
5. Gastric Cancer (up to 46-94%)
6. Gastric MALT lymphoma
Gastric Cancer
- MC gastric adenocarcinoma
- Primary malignancy
- Arise from gastric epithelium & can occur in any portion of the stomach
- 2nd MC cause of cancer death worldwide (bc usu asymptomatic until advanced)
- Poor prognosis
- Tumor infiltrates mucosa → can develop into the lumen → can penetrate adjacent organs (liver, pancreas, esophagus, duodenum)
Gastric adenocarcinoma
- Diffuse type gastric poorly differentiated adenocarcinoma more assoc w/ genetic abnormalities

f
o Germline mutations of CDH1 gene → encode E-cadherin (cell adhesion molecule in normal cell diff/tissue structure)
- Intestinal type gastric well-differentiated adenocarcinoma also influenced by env factors
o H. pylori, high salt consumption, low gastric acid (high gastric pH), inflammation (IL-1, TNF-a), strong expression of
TFF2 (trefoil factor family)
Intestinal gastric cancer
- Some mutated genes promoting dysplasia:
o Inactivated APC tumor suppressor gene (tsg)
o TP53 t.s.g
o KRAS oncogene (tobacco smoke mutate it)
o NF-kappa B activation (dna transcription factor for cytokines for inflamm, GF, anti-apopyoyic & promote angiogenesis)
- Some genes promoting adenocarcinoma:
o ERBB2 (HER2)
o Human epithelial GF receptor 2 (HER2) proto-oncogene OVER EXPRESSION
▪ Member of EGF receptor family
o Wnt/beta-catenin pthwy (cell-cell adhesion)
Gastric lymphoma
- RARE
 - Primary malignancy
- MC of primary gastric lymphomas are NH B-cell lymphomas consisting of mucosa assoc lymphoid tissue (MALT) & large B-cell
lymphoma
o NF-Kappa B activation
- Diffuse large B-cell lymphoma
o Bcl-6 oncogene over expression

GB biliaryducts
- Assoc w/ H. pylori, HIV, EBV, Hep B virus
BMS 8.8.
CCK peptide hormone can
-
-
Secretion targets the smooth muscle of the gallbladder and biliary ducts
Promoting the delivery of bile and pancreatic enzymes into duodenum from prox small intes
- CCK secreted from proximal small intestine primarily when fats (some a.a.) move into duodenum
- Physiological effects
o *Emptying Gallbladder* - contract smooth muscle wall of GB and relax hepatopancreatic sphincter (oddi)
o Pancreatic exocrine – potent stimulator of enzyme secretion & weak stimulator of HCO3 secretion (can potentiate
secretin effects)
o Inhibits gastric emptying – relaxation of proximal stomach & contraction of pylorus
- CCK distribution & release
o Released from I-cells in duodenum & jejunum → produces all effects of gastrin at high doses
o Stimuli for release → lipid containing foods, peptides/single a.a., acid
(weak stim)
Secretin
- Released from S-cells of duodenal mucosa
- Stimuli for release → acid in duodenum (pH <4.5) & protein and FA in duodenum
antacid -
-
Inhibited → somatostatin
Physiological effects: Natures antacid
o Inhibits gastric acid secretion
o Stimulates pancreatic – induces bicarb secretion → neutralizes acid

611hr
chyme creating optimal condition (pH 7-8) for digestive enzymes
o Stimulate bile bicarb secretion
o Stimulate pepsin secretion
o Trophic effect on exocrine pancreas
Bile
- Bile = bile acids + bile pigments + other substances in alkaline electrolyte solution
- Liver excretes lots per day
- Some components are REABSORBED in intestine & excreted again by the liver (enterohepatic circ)
- Role of bile: digestion & absorption of fats + excretory route for lipid soluble waste products
Bile salts
- Amphipathic nature enables bile to perform 2 fn essential for fat digestion & absorption
o Emulsification of lipids – detergent action, cause fat to remain as microscopic droplets to be digested effectively
o Transport of lipids – bile salts carry lipids (monoglycerides, FA, cholesterol) to intestinal wall in form of micelles
- Recycles via enterohepatic circulation
- Cholic acid (hydroPHOBIC) + glycine (hydroPHILIC) → glycholic acid (amphipathic)
BMS 8.10 The student will describe the anatomy of the parietal and visceral peritoneum, its lesser and greater sacs, mesenteries,
peritoneal ‘ligaments’, and the significance of the variable attachment of the ascending and descending colon to the posterior abdominal
wall.
Micelles
- Ingest dietary fats/neutral fat (TGs)
- FA are surrounded by bile salts
o Helps fat globule break into smaller pieces via emulsification micellesintestinal
o
o
Lipase enzyme works better on small fat globule to release FA from TGs
Bile salts surround the FA molecules & stops FA molecules from reforming into globules cells abs of
FA
o Micelle moves towards cells of the intestines for absorption of FA (bile salts are recycled)
- Bile acids & FA interact = micelle (cylindrical)
-
-
Contain FA (varying concentrations), cholesterol, & monoglycerides
FA can now be transported to intestinal enterocytes (intestinal epithelial cells)
enterghpati
- FA diffusion out of micelle & into mucosal cells

0
- Bile salts DO NOT enter intestinal cells but are recycled
Enterohepatic circulation
- Fate of ABSORBED bile salts:
o bilesalts Sm intes liver
Majority of bile salts circulate b/w small intestine & liver (recycled)
o Small amnt of bile salt move into systemic circ (incomplete hepatocyte uptake from portal blood)
o Small amnt of bile salts move into colon (excreted in feces)
BMS 8.11 The student will identify and describe the vascular components of the abdomen including the course and major branches of the
abdominal aorta, the major arterial blood supply to each organ, various regions of the small intestines, cecum and colon, and the
anatomic organization and purpose of the portal venous system.
Abdominal Aorta
- Celiac trunk → common hepatic a. → hepatic proper a. → R/L hepatic a. & R gastric a.
- Celiac trunk → common hepatic a. → gastroduodenal a.
- Celiac trunk → left gastric a.
 - Celiac trunk → splenic a. → pancreatic a.
Inferior Vena Cava
- Largest vein in the body
o R/L common iliac veins
o On R → 3 veins approx. at R kidney drains directly into IVC: R. renal v, R gonadal v., R suprarenal v.
o On L → at kidney level, only L. renal v. drains directly into IVC: L renal v. into IVC
▪ L gonadal v. into L renal v. → IVC

splanchniccirc
▪ L suprarenal v. into L renal v. → IVC
- Blood travels through IVC in the liver → DOES NOT TRAVEL IN PORTAL system
- R, middle, L hepatic veins drain into IVC at diaphragm
- Where are the veins draining systemic blood from the abdominal organs?
o Kidneys, suprarenal glands, gonads, diaphragm, posterior abdominal wall → directly into IVC (systemic circ)
o Veins that connect to these organs are draining systemic blood
BMS 8.12
Biliary obstruction
- Blockage of any duct that carries bile from liver to GB or from GB→ small intestine
o Cholestasis = failure of biliary flow
▪ Metabolic factors in hepatic cells (no known patho)
▪ Mechanical failure (intra/extrahepatic – below)
- INTRAhepatic (liver itself)
o Primary biliary cirrhosis
o Primary sclerosing cholangitis
- EXTRAhepatic
o Biliary atresia
o Gallstones
▪ Cholelithiasis – stones in GB, not considered a disease unless they cause symptoms
▪ Gallstone dz – refer to gallstones that cause sx
o Strictures – atresia, iatrogenic, inflammation (pancreatitis)
o Carcinoma of pancreatic head – CBD runs through head of pancreas
Primary Biliary cirrhosis
intralob -
-
Chronic cholestatic dz due to dmg to intralobular (intrahepatic) bile ducts by chronic granulomatous inflammation
Unable to excrete bile → present w/ malabsorption of fat-soluble vitamins & w/ evidence of portal HTN
- PATHO→

ayetana
o Characteristically a granulomatous destruction (scarring) of bile ducts
o Cu accumulates in hepatocytes due to chronic cholestasis
▪ Chronic inflammation in portal tracts
▪ Portal fibrosis progresses to cirrhosis
Primarily sclerosing cholangitis (PSC)
- Chronic cholestatic dz due to a non-specific inflammation & fibrosis of bile ducts, intrahepatic & extrahepatic ducts
o Inflammation, fibrosis, & strictures of biliary tree
- PATHO→
o Concentric fibrosis of bile ducts → may result in scar at site of duct
o Possible Cu accumulates in hepatocytes
o Usu scanty lymphocytic infiltrate
o Portal fibrosis progresses to cirrhosis
Cholangiocarcinoma (inside duct in liver)
- Cancer originating from epithelial lining of biliary tree (ducts)
- Rare but poor prognosis
- More likely to result in:
o Chronic problems w/ biliary tree – extrahepatic & intrahepatic ducts
o Primary sclerosing cholangitis
o HBV, HCV
- PATHO→
o No inherited
o Somatic genes:
▪ Extrahepatic CCA → TP53 t.s.g & KRAS oncogene
▪ Intrahepatic CCA (MC)→ TP53 t.s.g & KRAS oncogene (worst prognosis)
Extrahepatic Biliary Atresia
- Complete obstruction of bile flow due to destruction or absence of all or part of the extrahepatic bile ducts
- PATHO→
o Bile duct proliferation or loss of ducts
o Portal edema
o Fibrosis (may or may not be present)
o If untreated → cirrhosis
Neoplasia development
- Adenoma → BENIGN develop from glandular structures /tissue in epithelial tissue→ in hollow organs like digestive tract
adenoma grow into lumen
- *Carcinoma* → MALIGNANT develop from ectodermal or endodermal tissues (include all epithelia tissue cancers) →
carcinomas are majority of all cancers & generally divided into squamous cell or adenocarcinoma
 o Adenocarcinoma → further atypical, now MALIGNANT dev of glandular tissue (adenoma) esp of breast, uterus,
prostate, lung, esophagus, stomach, colon, rectum, pancreas → some adenomas transform into adenocarcinomas & more
common in mucus membrane (GI, resp, GU & Repro)
- Sarcoma→ MALIGNANT dev from mesodermal tissue thus predominantly CT cancers → cartilage, bone, blood (bone marrow)
Pancreatic cancer genetics
- Two basic types → endocrine vs exocrine
o Ductal carcinoma/adenocarcinoma → MC / EXOCRINE
▪ MC in ducts of head of pancreas
▪ Activation of oncogene→ ras family (KRAS)
▪ Inactivation of t.s.g. → CDKN2A (for p16), TP53 (p53 & cell signal), NOTCH (protein NOTCH1) & is under
control of p53 protein
• NOTCH also assoc w/ ALL & thyroid cancer
▪ Deregulation of signal pthwy of TGF-beta → SMAD4 gene
o Neuroendocrine tumors → ENDOCRINE
▪ Gastrinomas → found in duodenum, pancreas, or LN near head of pancreas 19
• Several gene assoc but recently linked to mutation in DNA repair gene BRCA2
▪ Assoc w/ multiple endocrine neoplasia type-1 (MEN-1)

[Link]
• MC MEN-1 tumors → PTH gland, pancreatic islets & pituitary gland
• Result of germline mutation of t.s.g MEN-1
o MEN-1 interacts with NF-kappaB
- Many germline mutations:
o BRCA2 t.s.g & helps repair dmg genes
▪ Inherited variants of BRCA gene lead to inc cancer risk
▪ Besides pancreatic cancer → inc risk of prostate, melanoma, [ovarian, breast, & uterine] [inherited BRCA2]

o
in ▪
▪
BRCA1 gene variants
BRCA1/2 assoc w/ hereditary breast and ovarian cancer → inc risk for female and male breast cancer
and ovarian cancer
PALB2 → work w. BRCA to help repair change in DNA → inc risk of breast cancer
o ATM t.s.g → inc risk of breast cancer
BMS 8.13 The student will describe the biliary system and the anatomic relationships between liver, gallbladder, pancreas and
duodenum with respect to this system.
Circulation through Liver
- A lot of cardiac output flows through liver with only 9mmHg difference in pressure
o Low resistance, low pressure, & high flow
o Blood reservoir function
o High lymph flow

cystic duct bile

o Macrophage system – Kupffer cells
o Cirrhosis increases resistance
Exocrine ducts
- Cystic duct, common hepatic duct, common bile duct, & pancreatic duct

-
-
o Major/ minor duodenal papilla, hepatopancreatic ampulla
Common bile duct → gastric duct + common hepatic duct
Liver = makes bile (not gallbladder)
Foster
- GB= bile is stored
- Cystic duct → bile goes both ways
- Pancreatic duct ENTERS, with the common bile duct (hepatopancreatic duct), into the duodenum* (ALWAYS)
Gallbladder (72)
- Controlled by CCK and ACh
- VIP (vasoactive intestine polypeptide) → promote fluid secretion
- Bile duct → non nerve transmission
Pancreas (104)
- Pancreatic acinar cells → EXOCRINE → pancreatic juice
- Pancreatic islets (of Langerhans) → ENDOCRINE → insulin & glucagon
BMS 8.14 The student will identify the position, key anatomic relations and histology of the lobes of the liver.
Liver
- Coronary ligament: peritoneal reflections that hold the liver to the inferior surface of the diaphragm
- Falciform ligament: derived from the ventral mesentery & forms a connection b/w the ventral abdominal wall & the liver, separation
between R/L lobes
- Round ligament of the liver (ligamentum teres or ligamentum teres hepatis): is a degenerative string of tissue that exists in the
free edge of the falciform ligament; it was the umbilical vein in neonate development
- Functions:
o Essential for life o Glycogen storage
o 1.5kg (2.5% body weight) o Hematopoiesis (fetus)
o Metabolic activity o Bile production
o Plasma proteins o Immunity
o Detoxify blood
- More functions:
o Carbohydrate metabolism o Synthesizes plasma proteins, non-essential
o Detoxifies endogenous and exogenous a.a., & vitamin A
toxins in plasma
 o Stores essential nutrients (vit K, D, B12, & o Secretes bile
Fe) o Processes Hgb for utilization of its iron
o Remove ammonia from body fluids (urea for content
excretion) o Regulate blood clotting
o Regulate BGL by storing glucose and
releasing as needed
- Now she says “Main functions:”
o Formation & secretion of bile
o Nutrient & vitamin metabolism
o Inactivation of various substances
o Synthesis of plasma proteins
o Synthesis of clotting factors
- Fissures: (visible on posterior view)
o Umbilical (left sagittal) fissure → separate left lobe from caudate lobe & quadrate lobe
o Porta hepatis → separate caudate lobe & quadrate lobe
o Right sagittal fissure → separate right lobe from caudate lobe & quadrate lobe
- Quadrate lobe is on the angled edge
- Caudate lobe is on the flat edge
Gallbladder
- Stores & concentrates bile
- 60ml of concentrated bile
- Concentrates bile salts – GB mucosa absorbs water and most electrolytes (not Ca)
- Cholecystectomy – surgical removal of the GB
Cholelithiasis (common) – gallstones in the GB W/O INFLAMM
- Majority are asymptomatic
- Five Fs→ fat, forty, female, fertile, (fair)
- Composition of bile: (most to least %) – bile salts, phospholipids, cholesterol, bile pigments, electrolytes, water
- If composition not ideal → cholesterol crystals (MC yellow) or bile stone formation from too much bili (brown/black)
o Sludge → microlithiasis; bile remains in GB for too long + mix w/ mucus → sludge on US
- Formation of gallstones →
o Cholesterol is highly INSOLUBLE & can precipitate in bile forming gallstones
▪ Imbalance of bile salt/cholesterol ratio
o Causes of cholesterol precipitation
▪ Too much→ water reabsorbed, absorption of bile salts or lecithin, or cholesterol
o Amount of cholesterol in bile related to fat intake → high fat diet = promote dev of gallstones
- Plain film view
o Contain Ca → radio opaque stones
o Contain cholesterol → radiolucent (cant be seen on plain films)

Cholecystitis – inflammation of GB due to gallstones

- Stasis of bile from persistent cystic bile duct obstruction leads to inflamm w/in GB
- Bile is prevented from leaving GB & acts as irritant
o Cellular infiltration w/in 3-4d
CYSTI o
o
GB enlarged and edematous
Lead to occlusion
DULT -
o Bile stasis can lead to necrosis of mucosal lining
Inflammation of GB by lysolecithin & nearby abdominal wall (not obstruction alone – need release of inflamm mediator)
o Lysolecithin →secretion promote inflammation
o Other pro-inflamm cytokines & PGs can also promote inflamm
- Can lead to bacterial infections→
o Gram + = enterococcus
o Gram - = K. pneumo (Enterobacteriaceae) or E. coli
- Inflamed GB stages (empyema, gangrene, perforation)
o Grayish and edematous, obstruction of cystic duct and GB begin to swell, no longer robin egg blue
o As progresses → become necrotic, speckled as wall begins to die (GB empyema ?)
o Rare → gangrenous change & very dark green or black, perforation occurs here → can lead to peritonitis

result
Complications of Gallstones
- Choledocholithiasis
o Gallstones in CBD
▪ Primary – stones FORMED w/in CBD, LC, caused by bile stasis (CF pts)

inappin o
o
▪ Secondary – stones PASS from GB into CBD, MC, associated duct dilatation
Result in inflamm or infxn of ducts
Complication is biliary pancreatitis
- Ascending cholangitis (bacteria travel from duodenum)
o Inflamed bile duct
o Biliary tract infxn usu due to CBD obstruction
o Inflamm/bacterial infxn superimposed on an obstruction of biliary tree

in19h1m
▪ MC occur w/ gallstones
▪ was
May be assoc w. neoplasm or stricture post-op
 o Biliary obstruction inc intrabiliary pressure → inc permeability of bile ductules → bacteria & toxins translocate from
portal circ into biliary tract
▪ If pathogen → MC = [Link], Klebsiella, & enterococcus
o Elevated pressure favor migration of bacteria from bile into SYSTEMIC CIRC
o Sphincter of Oddi reflux
- Pancreatitis (complication of CBD obstruction)

BMS 8.15 The student will describe the major functions of the liver including the production and secretion of bile salts and bilirubin.
Hepatic portal system → entrance to liver
- Created when two veins join → superior mesenteric v + splenic v.
o Inferior mesenteric v. joins splenic v. (drains into)
- Dual blood supply:
o Hepatic portal vein (MOST): nutrient rich & oxygen POOR blood from gut
o Hepatic artery (LESS): oxygen rich blood
- Blood drains into sinusoids for both hepatic portal v. & hepatic a. → toward central v. (liver lobules) → hepatic v. (R,M,L) → IVC
- Kupffer cells line sinusoids (immune defense)
- Interior mesenteric v. branches → L colic v, sigmoid v, superior rectal (portacaval anastomosis)
- Superior mesenteric v. branches → R. colic v., ileocolic v., middle colic v.
Hepatic portal system → exit
- 3 hepatic veins all drain into the IVC = R, middle, L hepatic v.
- Each liver lobule has 1 central v. → eventually drains into R,M,L hepatic v.
Liver vascular duct system
- Portal triad @ periphery of liver lobules:
o Branch of hepatic portal v.
o Branch of hepatic artery (hepatic artery is a SYSTEMIC artery)
o Bile duct
- Blood drains into the sinusoids:
o Branch of hepatic portal v. → oxygen poor but nutrient rich
o Branch of hepatic artery → systemic artery (oxy rich)
o Bile duct → carries bile towards hepatic ducts → flow in oppo direction as blood
Bilirubin
- Water INSOLUBLE product of heme metabolism (breakdown of RBCs & Hgb)
o Heme poorly water soluble so bound to albumin in plasma
- Taken up by liver + conjugated to become water SOLUBLE so it can be excreted in bile and bowel
o Released into gut in bile → most bile excreted in stool & some bile reabsorbed (reused)
o Released in circ to be excreted by kidneys
- Pt looks jaundiced if inc bili
- Kupffer cells = resident macrophage cells, helps in breakdown of heme
- Heme → biliverdin → bilirubin (all in RES) → bili-albumin →liver → conjugated bili → small intestine → urine or feces
o Stercobilin→ feces
o Urobilinogen → kidneys → urine
BMS 8.16 The student will describe the metabolism of bilirubin following RBC breakdown including subsequent excretion into the
intestinal tract via the biliary tree; differentiate conjugated from unconjugated bilirubin; and predict how this will manifest clinically
and with laboratory studies in the context of hypo- & hyperbilirubinemia and underlying disease processes.
Bili blood test
- Total bili = direct (conjugated) + indirect (unconjugated)
- Indirect = unconjugated

unconj insoluble
o Heme is released from Hgb converted to unconjugated bili
o Carried by albumin → liver
o Small amounts present in blood
o Water INSOLUBLE
- Direct = conjugated
o Formed in the liver when carbs are attached (conjugated) to bili (making it water SOLUBLE)

conj Soluble
o Secreted in bile and passes from liver to small intes → excreted in feces/urine (rate limiting step)
o Usu NO conjugated bili present in blood
- Accumulation of bili → jaundice
Direct & indirect bilirubin
- Prehepatic dz: (hemolysis), causes high bili which is unconjugated (indirect fraction higher)
- Hepatic dz: increased conjugated &/or unconjugated bilirubin
- Post-hepatic dz: (gallstones), have increased conjugated (direct) bilirubin & lead to dark urine & pale stool
Unconjugated hyperbilirubinemia
- Production exceeds elimination
- Result of:
o Increased bili formation → hemolysis or ineffective erythropoiesis (megaloblastic anemia or iron defieciency)
o Failure of bili uptake → gilberts dz = def glucuronyl transferase
o Failure of bili conjugation → neonatal jaundice or extensive hepatocellular disease (hepatitis, cirrhosis)
Conjugated hyperbilirubinemia
- Production exceed elimination
- Result of:
o Liver is able to conjugate bili but excretion is impaired
 o Failure of bili excretion by hepatocytes
o Obstruction to biliary flow (cholestasis – both intra/extrahepatic)
BMS 8.21 The student will correlate the pathophysiology of commonly encountered GI diseases throughout the GI tract.
Synthesis of plasma proteins by liver
-
-
Albumin = majority of plasma oncotic pressures into cap back
Acute phase proteins = synthesized & secreted in response to stressful stimuli
- Steroid/hormone transport proteins
- Clotting factors
o Coagulopathy = any disorder of blood coagulation
o ALL coag factors EXCEPT VIII & Ca are produced in the liver **********

SNOT
o Vitamin K dependent factors = II, VII, IX, X************
- Only class NOT synthesized by the liver → immunoglobulins
Digestion of proteins [enzymes b/w rxn]
- Proteins - - [pepsin] - → proteases, peptones, polypeptides - - - [trypsin, chymotrypsin, carboxypolypeptidase, proelastase] (from
pancreas) -- → polypeptides + a.a - - - [peptidases] -→ a. a.
- Proteolytic enzymes are activated and destroyed very rapidly

trypsinogenestrypsin
o Enterokinase → activate trypsinogen
o Trypsin is autocatalytic (activate trypsinogen → trypsin)
rhltimferitedapid o
o
Trypsin activates other proenzymes
Proteolytic enzymes digest themselves
Activation of proteolytic enzymes
- Trypsinogen → trypsin (by enterokinase, but also by trypsin)
- Trypsin = autocatalytic activation of chymotrypsin(ogen), pro(carboxypeptidase, and trypsin(ogen)
- Enterokinase – located on intestinal mucosal cells
o Mechanism to avoid activation of pancreatic proteases until they are in duodenal lumen
o When juice enter duodenal lumen, trypsinogen contacts enterokinase expressed on apical surfaces of enterocytes
o Trypsinogen → cleaved to trypsin → activate additional trypsin molecules as well as remaining proteolytic enzymes
- Pancreatic enzymes → activated by trypsin
o Trypsinogen → trypsin
o Chymotrypsinogen → chymotrypsin
o Proelastase → elastase
o procarboxypeptidaseA → carboxypeptidase A
o procaboxypeptidase B → carboxypeptidase B
Acute pancreatitis
Masis
pancremicenmmesactivnrgb [Link]
- Acute inflammatory process of the pancreas
-
-
Can be caused by anything that injures the acinar cells
I
Injury or disruption of pancreatic ducts (obs. Pancreatic outflow MC by gallstones) →leak of active pancreatic enzymes in pancreas
(secreted from acinar) → AUTODIGESTION (breakdown of cell membrane)
- Acinar cells are exocrine cell of pancreas → produce enzymes + transport them into pancreatic ducts
- Any acinar cell injury → pancreatitis →
Acinar cell injury → intracellular activation of pancreatic enzymes → autodigestion of pancreas → edema, interstitial

airfield
o
hemorrhage, coagulation, & cellular fat necrosis
-
-
Alcohol = inc sensitivity to CCK →stimulate production of pancreatic enzymes
PATHO→ an pancrearicemosme
o Premature activation of trypsin → autodigestion of pancreatic tissue → activate inflamm response → inflamm mediators
(vasodilation) & extravascular movement of albumin (pancreatic edema) → SHOCKKKKK
o Autodigestive effects of pancreatic enzymes:
▪
▪ D
Trypsin – digests the pancreas → mutation of PRSS1 gene (BAD)
Elastase – dissolve elastic fibers of blood vessels → hemorrhage a press lidelt
Pancreas by
▪ Phospholipase A – fat necrosis, lipoprotein metab from hyperTGemia
▪ Lipase – fat necrosis
Chronic Pancreatitis

trypsin
- Continuous, prolonged inflamm, & fibrosing process of the pancreas
o Toxic metabolites can upreg apoptotic genes
o Pancreas becomes destroyed as it is replaced by fibrotic tissue
o Strictures & calcifications can also occur
- Chronic calcifying pancreatitis
o Ducts are obs w/ protein precipitates
o Precipitates block pancreatic duct and eventually calcify
o Calcification → fibrosis & glandular atrophy n
BMS 8.22 The student will investigate the pathophysiologic mechanisms of the following manifestations of chronic liver disease
Hepatitis
- Inflammation of the liver
o Mononuclear response destroys liver architecture
o Necrosis of hepatocytes

bilirubin excretion
- Liver excretion of bili into intestine is interrupted
- Caused by:
o Viruses – hepatitis A, B, C, D, E
Other infxns (mononucleosis)
interrupted
o
o Autoimmune
 o Chemicals – alcohol & acetaminophen
- Acute = IgM is first ab made
- Chronic = IgG
- Acute infection secretes IgM ab & if chronic secretes IgG ab
- EBV, CMV, Herpes can all cause acute hepatitis esp in immunocompromised
EBV
- HHV-4
- Enveloped DsDNA virus

HHV'd - Herpesviridae family

brey UFA 3 ICAM 1

-
-
Icosahedral outer shell
b
Replicates in epithelial cells of oropharynx & in B lymphocytes
o Transmitted by exchange of saliva
- Primary agent of infectious mononucleosis
- Asymptomatic EBV shedder→ silent subclinical infxn for life
- The virus replicates continuously in the body at very low level (persistence)
o Down-regs cell adhesion molecules involved in immune recog → LFA-3 & ICAM-1
CMV
- HHV-5

HHV 5
- Enveloped, DsDNA virus
- Herpesviridae family
- Icosahedral outer shell
- Replicates mainly in salivary glands & kidneys (shed in saliva and urine) → replication is SLOW
- Chronic infxn = silent subclinical infxn for life
o The virus replicates continuously in the body at very low level (persistence)
Viral hepatitis A (HAV)
- Hep A (infectious hep or HAV)
- RNA virus
o Viral replication occurs in the hepatocyte cytoplasm
o Leads to apoptosis of hepatocytes (viral replication occurs in hepatocyte cytoplasm)
- Anti-hepatitis A IgM-HAV ab present during acute illness (host response to HAV)
o Dark urine/pale stool then jaundice
- No chronic sequalae (self-limited)
at - Fecal-oral transmission
Viral Hepatitis B (HBV)
- Serum hepatitis or HBV
- DNA virus ***
- Antibody HBsAg = surface antigen (indicates first sign of infxn)
o Anti-HBs = appears after clearance or vax
- Antibody HBeAg (envelope antigen) = indicates viral replication
o Anti-Hbe = antibody to HBeAg

MID
- HBcAg – core antigen
o Antibody to the core antigen = anti-HBc
o Anti-core IgM (IgM anti-HBc) → is present during acute phase
o Anti-core IgG (IgG anti-HBc) → indicates chronic infxn
- Hepatocellular necrosis occurs due to body’s rxn to the virus rather than due to the virus itself
- Acute illness = jaundice
- Chronic illness = can result in cirrhosis, hepatocellular carcinoma
- Transmission:
o Transfusion, transplant recipients
CS e aunte

196 EE chronic
o Mother-child
o Blood-exposure
- PATHO→
o Viral DNA (HBV) or RNA (HCV) is integrated into host cell genome
▪ HBV sequences are present in HCCs
o One gene may have important promotional role in hepatocarcinogenesis, but the mechanism is not yet known
Viral Hepatitis C
- Hepatitis C (HCV)
- RNA virus

RNA
o Acute infxn typically asymptomatic
o Chronic illness can result in cirrhosis & hepatocellular carcinoma
o Transmission: blood (needlesticks, transfusion), body piercing/tattoos, HIV infxn
o No vax available
o Chronic Hepatitis C & alcoholic liver dz is two MCC of liver dz
Hepatocellular Carcinoma
- Liver cancer
- Hepatocellular carcinoma (HCCs) are malignant (aggressive) tumors of liver parenchymal cells
o Occurs predominantly in pts w/ underlying chronic liver dz +/- cirrhosis
- Transformed cells
o Lose contact inhibition
o Continue to divide
 moreHcc
o
o
Form random aggregations
Can become invasive
Chronic Hep B
- PATHO→
o Hep B/C virus probable cause in most cases
o Chronic HBV infxn much MC in HCC cases
o Cirrhosis is closely related w/ chronic HBV infxn & most liver cancers occur in cirrhotic livers
o Some alterations in chromos & mutations in mult genes possible
Viral Hepatitis D (delta)

RNA -
-
-
Incomplete RNA virus
Needs HBV infxn (HBsAg) to infect (co-infxn)
low risk of chronic infxn
Viral Hepatitis E (HEV)
- RNA virus
- Uncommon in the US
- Acute infxn: generally self-limiting
- Transmission
RNA o
o
Fecal-oral (contaminated water)
Undercooked meat from infected animals
o Blood transfusion
Autoimmune Hepatitis
- Syndrome of chronic hepatitis in pt w/ heterogenous set of immunological abnormalities
- PATH→

fat in
o Dec # & fn of suppressor t lymphocytes

at hepatocytes
o Cytotoxic T-cells attack hepatocytes (VIRAL)
o Fibrosis (may or may not be present)
o Necrosis w/ lymphocyte infiltration
Cirrhosis
- Chronic liver disease in which normal liver cells are damaged & replaced by scar tissue
o Progression from liver fibrosis (stage prior to cirrhosis)

Hepc
o MCC→ HCV, alcoholic liver dz, & nonalcoholic liver dz
o Alcohol abuse leads to accumulation of fat w/in hepatocytes
o Fatty liver leads to steatohepatitis
▪
▪
Steatohepatitis = fatty liver + inflammation → scarring of liver and cirrhosis
Steatosis→ deposition of adipose
Cirrhosis
o When hepatocytes are destroyed, can regenerate but increases CT
- Four stages:

fibrosis
o Liver cell necrosis
o
o
Inflammatory cell infiltrate
Fibrosis (collagen deposition)
necrosis inflamm regen
o Nodular regeneration → macronodular (alcohol) or micronodular (viral) or mixed
- Complications
o Jaundice (yellow from bili retention)
o Portal HTN
o Ascites (fluid accum in abd)
o Peripheral edema (→ hypoalbuminenia)
o Bleeding esophageal varices (varicose veins in esophagus)
o Blood coag abnormalities
▪ Splenomegaly
o Hepatorenal syndrome
o Coma & death
Portal HTN
- Increase in portal venous pressure gradient
o
o
Defined as elevation of hepatic venous pressure gradient >/=5mmHg
Hallmark of cirrhosis 5mm Ng HTN
- Rise in intrahepatic vascular resistance
o
o
o
Increased BP in sinusoids
Loses low pressure character
blood can pool in splanchnic circulation
b
- hepatic portal veins LACK VALVES
o
o
elevated pressure transmitted backwards
backflow into spleen (splenomegaly) & portal-to-systemic vessels
cirrhosis
- Complications
o Variceal hemorrhage → due to portal HTN

2
▪ Varices – dilated submucosal veins at portal-systemic anastomoses
Portacaval anastomoses → where portal circulation meets systemic circulation
o Esophageal branch of L gastric v = esophageal varices
o Paraumbilical v. = caput medusa, opening of normally closed umbilical vein
 o Colonic v. & splenic v (splenorenal varices)
o Sup. Rectal v. = rectal varices
Hypoalbuminemia
- Decreased production/concentration of albumin
- PATHO→
o Decrease in plasma oncotic (colloid osmotic) pressure
o Increases pressure gradient towards filtration (&
decreases reabsorption)

RASDBOP BAP ▪ Leads to development of edema &

(fluid in peritoneal cavity)
ascites

o Elevated aldosterone secretion (from RAS)

▪ Low serum K
Ascites formation
- Accumulation of fluid in the peritoneal cavity
- PATHO→→→
Alcoholic liver disease & cirrhosis
- Inflammation of the liver due to excessive alcohol changes the in cells & environment (matrix) of the liver → fibrosis
- Associated w/
o Alcohol fatty/steatotic liver disease (ASLD)
o Alcoholic (steato)hepatitis (ASH)
o Cirrhosis
o Hepatocellular carcinoma
- Alcohol is significant RF for liver cancer in areas w/ low HBV & HCV incidence

- PATHO→
o Alcohol → cirrhosis → inc risk of HCC
all endothelins myofibrobla
o
o
Alcohol release → endothelins from sinusoidal endothelial cells
This induces myofibroblasts to contract, constricting sinusoids & leading to localized hypoxia, further damaging factor b
- Alcohol increases AST synthesis; vitamin B6 def inhibits ALT
Nonalc fatty liver disease
contrac
-
-
Prescence of hepatic steatosis when no other causes for hepatic fat accumulation are present
+/- inflammation or fibrosis b
hypoxia
- Subdivided into:
o NAFL – nonalcoholic fatty liver (no inflammation)
o NASH – nonalc steatohepatitis (inflammation)
- PATHO→ may be tied to insulin resistance
Hemochromatosis
- Hereditary hemochromatosis (HH) → too much iron in the blood
- Due to mutations in HFE gene
Feoverled -
o HFE protein plays an important role in the process by which duodenal crypt cells sense body iron stores
Autosomal recessive
- Increased intestinal iron absorption
o Increased serum Fe, increased hepatic Fe, increased total body Fe, progressive tissue injury → cirrhosis, organ failure
Wilson disease
- RARE, autosomal recessive disorder

anorerload
- Too much Cu
o ATP7B → copper transporting ATP ATP713
- Excessive deposition of copper in the liver and brain
o Also, in the cornea & kidney
o Can lead to splenomegaly, hemolytic anemia, portal HTN, neurologic, & psych abnormalities
- PATHO→
o Excessive absorption of Cu from the small intestine
o
o
Decreased excretion of Cu by the liver
Increased tissue deposition
Renans excretion tissue
Hepatic phagocytic system
- Liver RES is comprised of tissue macrophages (Kupffer cells)
- Kupffer cells (RE cells) are in liver sinusoids

unpferonsdetox
- Main cellular system for removal of particulate materials and microbes from circulation
- Removes 99% of bacteria from gut that flows to liver through portal system
Hepatic encephalopathy (portosystemic encephalopathy)
- Cirrhosis & portal HTN can lead to increased susceptibility hepatic encephalopathy
o Results in neuropsychiatric abnormalities
▪ Personality change
▪ Intellectual impairment
▪ Depressed level of consciousness
- PATHO→ portal blood diverted to systemic blood through collateral vessels
o Leads to neurotoxins damaging/passing the BBB such as ammonia
- Ammonia = toxic to CNS
o Freely permeable to cross BBB
o Primarily comes from colon & kidneys

NHz coloniidmys
o Lesser amounts from breakdown of RBCs & muscle metabolism

y
RBCS
 - Liver = only organ in which complete urea cycle is expressed
o Converts ammonia → urea → excretion through urine
BMS 8.4
Autonomic nervous system → GI
- External anal sphincters → somatic nervous system (skeletal muscle)
- Periarterial extensions can carry postsynaptic sympathetic & PNS
o Periarterial extensions → the spreading network of nerve fibers and ganglia that extend from major autonomic nerve
plexuses along the arteries, innervating the artery walls and surrounding organs. Continuation of nerve plexuses on arteries
- Abdominopelvic = Thoracic splanchnic (greater [T5-9], lesser [T9-10], least [T12] ) + Lumbar splanchnic nerves [L1-3] →
presynaptic SNS
- Vagus (CNX) + pelvic splanchnic nerves [S2-4] → PNS
- Splanchnic nerves
o Greater, lesser & least splanchnic nerves → derive from LOWER thoracic splanchnic nerves (SNS)
o Lumbar splanchnic nerves derived from abdominal part of sympathetic trunks (lumbar region of spinal cord, SNS)
o Pelvic splanchnic nerves → PNS (from sacral region of spinal cord)
o Splanchnic nerves
▪ Abdominopelvic
• Thoracic region (T5-12) → preganglionic SNS
• Lumbar region – coming off lumbar spinal cord not going to visceral organ→ preganglionic SNS
• Sacral region → preganglionic SNS
▪ Pelvic + CNX→ going to visceral organ → PNS
- Nerves to stomach & liver are from esophageal plexus
o Hepatic branch of CNX – from anterior vagal trunk & run w/ hepatoduodenal ligament
o Posterior & anterior gastric branches
o R/L CNX → vagal trunks
Innervation of colon
- SNS of descending & sigmoid colon
o Lumbar part of sympathetic trunk via LUMBAR splanchnic nerves → superior mesenteric plexus & peri-arterial
plexus following the inferior mesenteric a. & its branches
- PNS of descending & sigmoid colon
o Pelvic splanchnic nerves via inferior hypogastric (pelvic) plexus & nerves → ascend retroperitoneally from plexus
INDEPENDENT of arterial supply
Innervation of rectum
- SNS of rectum:
o Lumbar spinal cord via lumbar splanchnic nerves & hypogastric/pelvis plexus → use peri-arterial plexus of inferior
mesenteric & superior rectal a.
- PNS of rectum:
o S2-4 spinal cord level → via pelvic splanchnic nerves & L/R inferior hypogastric plexuses
BMS 8.6
Duodenum: Four parts
- Parts of the duodenum:
o First – superior part*
o Second – descending part (pancreas enzymes and bile dump in)
o Third – horizontal part
o Fourth – ascending part*
- Suspensory ligament of duodenum (ligament of Treitz - LOT) – surgical landmark
o Located in area of the 3rd/4th part of the duodenum
o Fibrous band by which the duodenojejunal junction is fixed to posterior wall of
abdominal cavity
▪ GI bleed: describe every form of hemorrhage in GIT from the pharynx to the
rectum
▪ UGIB: bleeding arising proximal to LOT
▪ LGIB: bleeding arising distal to LOT

Pliche circularis ISI

Small intestine: Mucosa or innermost layer (21-22)
- Mucosal layer – epithelium, vessels, lacteals, glands
o Mucosa of SI have villi that project into the lumen
o Villi ONLY in SI
- Circular folds – plicae circulares
Intestinal villi
villi
- Villi are projections (about 1mm) of the mucosa layer into the lumen predominantly w/ mature, absorptive
enterocytes, along w/ interspersed mucus-secreting goblet cells
- These cells live only for few days, die, and are shed into the lumen to become part of the material to be digested
and absorbed
- Increase SA 600x – 200-500m2
o Rugae (in stomach) : villi (SI) // gastric pit (stomach) : crypts (small/large inestines)
Small intestine crypt
- Crypts (of Lieberkukn)
- Villi are evagination while crypts are invaginations
- @ base of crypts are stem cells, which continually divide & provide the source of all the epithelial in the crypts & on the villi
- Small intestinal crypt Paneth cells w/ secretory granules, stem cells, enterocytes, & mucin secreting goblet cells
 SI crypt p anemons
hostdefense

- Paneth cells provide host defense against microbes in the small intestine – exposure to bacterial products leads to release of abx
peptides and proteins from Paneth cells
Kidney anatomy (41-42)
- Renal v → IVC
- Cortex = rine
Large intestine anatomy (61-62)
- Tenia coli → muscular band running length of cecum to rectum
- Haustra/haustral fold → pouches or small segmented area of colon due to folds of internal mucosa (visible on imaging)
Intraperitoneal (serosa) vs retroperitoneal (adventitia) organs

thanterseason
anammit

µg
stomach spleen
liver GB
Ileum
-
BMS 8.8
Jumps in and out of parietal layer, no visceral layer on those jejunum tail pancreas
Regulation
- Autonomic innervation
sigmoid
- Smooth muscle of muscularis externa → inner circular layer & outer longitudinal layer
- GI peptides (peptide hormones) → receptors are all G-protein coupled receptors (gastrin, CCK, secretin, GLIP/GIP, motilin, ghrelin)
- Hormones → endocrine cell from GIT → secrete → portal circ → liver → systemic circ → target cell
o gastrin, CCK, secretin, GLIP/GIP, motilin, ghrelin
o hormones use blood, have no ducts, and have to have receptor for it
- Paracrine → endocrine cell of GIT→ diffuse → target cell
o Somatostatin
o “Next to” → cell makes it and works on neighbor
- Neurocrine → neuron of GIT → action potential → target cell
o VIP
o Origin is nervous tissue
Chemistry of GI peptides (HORMONES)
- Two structurally related families:
o Gastrin family – gastrin & CCK
▪ 5C terminal AA identical
▪ Produce all effects of each other at HIGH doses
▪ Cholecystokinin – release pancreatic enzymes & trigger bile release
o Secretin family* - secretin, glucose dependent insulinotropic peptide (GLIP)/ gastric inhibitory peptide (GIP), &
glucagon
▪
▪
Some effects are shared
Secretin – neutralize acid GLIPGIP inhibgastricsec Stiminsuli
▪ GLIP/GIP – stimulate insulin secretion & inhibit gastric acid secretions (should be called GLIP)

in
- Enterogastrones – hormones released by upper intestinal mucosa (duodenum) in response to dietary nutrients
o Stimulated by → luminal FA, acid in duodenum, & hyperosmotic solutions
o Secretin, CCK, GLIP/GIP
- Motilin – chemistry = unrelated to other hormones
o Stimuli/release → released from M-cells in crypts of duodenum & proximal jejunum during fasting at intervals
▪ Stimulated by→ H+ in duodenum

minimum
o Physiological effects
▪ Stimulate upper GI motility (inc gastric emptying)
▪ Accounts for migrating motility complex, housekeeping contractions, improve
peristalsis & clear out gut to prepare for next meal
- Vasoactive intestinal peptide (VIP) (NEUROENDOCRINE)
vasodilation o
o
Chemistry – related to secretin
Stimuli/release → by H+ in duodenum
o Physiological effects: vasodilation, promote fluid secretion from bile duct, inhibit gastric

wind BMS 8.9

Incretins
secretion, & stimulate intestinal secretion

- GI hormones that work to increase insulin secretion:

o Substantially more insulin secreted in response to PO glucose vs IV glucose

ition insulinser
 lodecford
inhibit glucagon name
-
o Glucose activated a feedforward mechanism
Two main incretins:
o GLIP/GIP
delay gasticempty
o GLP-1 – glucagon like peptide 1 (35)
o Both hormones secreted by endocrine cells located in epithelial of small intestine
- Controlling eating
o GLP-1R agonist → mimic functions of natural incretin hormones in body that help lower post meal blood sugar levels
▪ Stimulate secretion of insulin
▪ Inhibits release of glucagon, gastric emptying, and food intake through inc satiety
- GLP-1 → works on intestines, stomach, pancreas, and brain
BMS 8.11

[Link] mesen suprec

Abdominal Blood supply (36-37)
BMS 8.17
Rectum arteries
- Superior rectal artery comes from inferior mesenteric a. (off abdominal aorta)
o Superior rectal a. descends into pelvis and its branches anastomose w/ middle + inferior rectal a.
- Inferior rectal a. comes from internal pudendel a.
o Internal pudendal a. is a branch of internal iliac a.
o Inferior rectal a. doesn’t have any branches but anastomose w/ middle + superior rectal a.
o Rectum also supplied by middle rectal a. which is branch of internal iliac a. – middle rectal a. often small or absent

mid Hu
Rectal anal lymph nodes
- Rectum:
o
intili
Superior rectal lymph → drain → inferior mesenteric lymph nodes
o Inferior rectal lymph → drains → internal iliac lymph nodes
- Anus:
o Above pectinate line → drain → internal iliac LN
o Below pectinate line → drain → superficial inguinal LN
Hemorrhoid cushion → rectal sinusoid plexus
- Hemorrhoid results from a dilation of veins
- Inferior rectal + middle rectal v. drain → internal iliac v.
- Superior rectal v → internal hemorrhoidal/rectal vein/plexus
Pectinate Line
- Anatomical anal canal → extends from the pectinate line to the anal verge (most is somatic)
- Surgical anal canal → begins at the anorectal junction; terminates at the anal verge (surgical repair area)
(top area is still autonomic)
- The pectinate (dentate) line also serves as clinical significance
o Above pectinate line, typically expect internal hemorrhoids & adenocarcinoma
▪ Internal hemorrhoids are not painful due to their visceral innervation (above pectinate)
▪ Lymphatics above pectinate → internal iliac nodes
o Below pectinate line, one can expect external hemorrhoids, anal fissures, & SCC
▪ External hemorrhoids are painful due to their somatic innervation (below pectinate)
▪ Lymphatics below pectinate → inguinal LN
BMS 8.18
Anterolateral Abdominal wall
- Linea alba = extend from xiphoid process to pubic symphysis
- Tendinous intersections – whitish looking fascia separating Rectus abdominis
Somatic nervous system → to skeletal muscle of abdomen
- Abdominal skeletal muscle actions on page 1
- Pyramidalis – (action) tenses linea alba
Hernia
- Hernia = abnormal weakness or hole in an anatomical structure which allows abdominal content to protrude through
o Commonly used to describe a weakness in the abdominal wall
o Due to weakened muscular wall/excessive strain, increase in intraabdominal pressure, congenital opening
- Hernias by themselves usu are harmless but nearly all have potential risk of having their blood supply cut off
- Locations =
o Inguinal (indirect – MC hernia// direct – MC acquired hernia)
▪ Direct inguinal (acq)→ near opening of inguinal canal, medial to inferior epigastric vessels

airfediastic
• Defect or weakness in the transversalis fascia area of the Hesselbach triangle or posterior wall of
inguinal canal of the anterior abdominal wall
▪ Indirect inguinal (congenital)→ at the opening of the inguinal canal, through internal ring (lateral to
inferior epigastric vessels)

o
o
•

Femoral – occur in the femoral canal, inferior to lingual ligament

Epigastric – upper abdomen at midline
11T
Inguinal canal opening fails to close completely by the time of birth, this allows a portion of fat
or intestine to slip through

o
o
Umbilical – at the naval
Incisional – at site of previous surgical incisional
epigasin
o Epigastric – upper abdomen at midline
- Hiatal – occurs when part of the stomach pushes through an opening (hiatus) in the diaphragm, the muscle that separates the chest
from the abdomen.
 - Femoral hernia – protrudes through the femoral canal; more likely to be incarcerated (thus more likely to require surgery)
o Bound by – inguinal ligament superiorly, femoral vein laterally, & pyriformis muscle and pubic ramus medially
- Umbilical hernia – results from improper closure of the abdominal wall defect where the umbilical cord was in utero
- Incisional hernia – abdominal wall defects that develop following abdominal operations
- Irreducible – usu painful & cannot be returned into the abdominal cavity on its own or when u push it
- Incarcerated – trapping of the abdominal content w/in the hernia sac (failure of the content to spontaneously reduce)
o Can progress to strangulated
- Strangulated – irreducible hernia where the entrapped intestine has its blood supply cut off (ischemia)
o Pain always present followed quickly by tenderness & sometimes sx of bowel obstruction (N/V)
o MEDICAL/ SURGICAL EMERGENCY

GAY
BMS 8.19
Peyer’s Patch in ileum
- Lymphocytes in the ileum peyer's

ir
2ndary lymphoid tissue → MALT

sutmuieloo ae
-

-
-
o MALT includes Gut associated lymphoid tissue (GALT)
Located in mucosa/submucosa path
Function → pick up antigen from intestinal lumen & present to lymphocytes (CD4, CD8, B cells)

0
- Located in mucosa (below the epithelium) in the ileum of the SI
Appendix
- 2ndary lymphoid tissue → MALT scattered along mucosal linings (includes GALT)
- Narrow, blind ended tube – attached at the opening of the cecum of large intestine
Acute appendicitis
- An inflammation of the vestigial vermiform appendix
- Obstruction of the lumen is the dominant causal factor
- Obstructing object can be → fecalith (appendicolith), lymphoid tissue hypertrophy, barium (from previous study), tumors, & seeds
BMS 8.20
Vomiting (emesis)
- Forceful expulsion of the contents of the stomach (& proximal small intestine)
o Toxin
o Incompatible food(s) – quality and quantity
o Chronic illness
o Normal body behavior (pregnancy)
- Voluntary or involuntary
- Categories of causes → GIT, sensory system, metabolic disturbances, pregnancy, drug rxns,
social cues, & self-induced
- PATHO →
o Stimulation of the area postrema chemoreceptors located on the floor of 4th
ventricle of the brain (brain stem controlled)
Water
- Stomach & colon absorb some water but MOST absorbed throughout SI → only 150mL
lost in feces daily
- 10L/d enter SI → 2L food/drink & 8L GI secretions (most absorbed across SI epithelium + 1L
enter colon)
- Any pathogenic alteration of INTESTINAL EPITHELIA greatly alter these #s → majority from acute infective diarrhea
Diarrhea
- Reflect increased water content of stool, either due to impaired water absorption & or active water secretion by the SI &/or
colon (water follows solutes into the blood capillaries)
o Lead to passage of abnormally liquid or unformed stools at an increased frequency
- From medical standpoint → diarrhea defined as stool weight of more than 200-250g in 24hrs
- CC of infectious diarrhea = MCC of diarrhea → most self-limiting
o Bacterial: (most are gram -)
▪ Cholera → Vibrio cholera, gram -, toxin producing strain, >200 serological groups
▪ Clostridium (Clostridiodes) difficile → gram +, toxin B more potent than toxin A,
▪ Traveler’s diarrhea:
• Shigella sonnei → majority infxn in US, gram –
• Enterotoxigenic E. coli → gram -, became pathogenic, MC traveler’s diarrhea
• Salmonellosis → salmonella typhi or paratyphi, gram –
• Campylobacter jejuni & coli → gram -, contaminated poultry
o Viral → Rotavirus
o Protozoa → Giardiasis (Giardia lamblia or duodenalis), also a form of traveler’s diarrhea
Types of chronic diarrhea
- > 4 weeks
 1. Osmotic diarrhea (malabsorption)
o Stool output PROPORTIONAL to intake of nonabsorbable substances
o Prescence of poorly absorbed luminal osmosis (i.e sorbitol) & extra amnt of water needed to dilute the ingested by
indigestible material (or retain fluid)
o Sorbitol = nonabsorbable solute, the lumen of colon
2. Secretory diarrhea (disordered electrolyte transportation)
o Entercolonic mucosa (epithelial cells) ion transport process turned into a state of active secretion
o Excess input of NaCl into lumen of colon → water follows salt
o Plasma dehydration & electrolyte imbalances are common
o Na is absorbed by epithelial cells (enterocytes) of SI → move toward/ through basal surface of cell → blood caps
o Water FOLLOWS Na + Cl in accordance w/ osmotic forces
o Decreased absorption of Na can lead to rapid Na depletion & DEATH
3. Inflammatory diarrhea (damage)
o Several mechanisms:
▪ Stimulated secretion & inhibited absorption due to release of cytokines / inflammatory mediators
• Stools → presence of leukocytes
▪ Stimulated enteric nerves causing propulsive contraction & stimulated secretion
▪ Mucosal destruction & increased permeability
▪ Nutrient mal-digestion malabsorption
o Crohn’s disease of the terminal ileum → inflammation damages the mucosa, reducing the SA for absorption
4. Motility related diarrhea (dysmotility causes)
o Large intestines not moving things through as they should
o Reduced contract time b/w luminal contents & bowel mucosa
o Increased bowel motility can lead malabsorption, urgency, & increased bowel sounds possible
o Post-vagotomy syndrome (dumping syndrome)
o Anxiety
o Bowel infection
5. Steatorrheal/reduced absorptive diarrhea
o Fat malabsorption → wt loss & vitamin def
o Increased fecal output caused by osmotic effects of FA
▪ Mucosal malabsorption → celiac dz
Colon
- Lacks microvilli, smaller SA → less absorption or secretion than SI → only transports about 1L of fluid per day
- Distention of colon stimulates contraction of the ileocecal valve to prevent fecal matter from moving back into the SI
- Movement through large intestine:
o Gastrolienal reflex → intensifies after a meal & occurs 3-4 times a day
o Haustral churning (pouches) → distension & contraction of haustra
o Peristalsis
o Mass peristalsis
Defecation reflex
- Loop diagram →
o Communication from the top down or bottom up (submucosal and myenteric
plexus)
o Help prevents from overstretching
- The urge to defecate is triggered when stool travels to lower rectum
- Spinal cord mediated PNS reflex
- Walls of sigmoid colon & rectum contract
- Internal anal sphincters relax w/ autonomics
- Feces forced into anal canal
- Brain notified → one chooses whether external voluntary anal sphincter should open
or constrict (somatic nervous system)
- Delayed defecation→ process can be mentally overridden →contraction of both sphincters → reverse peristalsis → drive poopie
back into sigmoid colon → remove stimuli to defecate
BMS 8.21
Small bowel obstruction
- Occurs when normal flow of intestinal contents is interrupted
- Obstructive PATHO→
o Progressive dilation of intestine proximal to blockage
o Decompression of bowel distal to blockage
o Bowel wall becomes edematous
 o Normal absorptive fn lost
o Can lead to dec perfusion, ischemia, necrosis, & perforation
- Mechanical (dynamic)
o Mechanical obstruction is one type of SBO preventing free passage of intraluminal material
o Partial or complete blockage in the intestine
o Blockage w/in the lumen or from outside of the lumen
o May be 2ndary due to →
▪ Extrinsic compression → adhesion, tumor, hernia (adhesion MC in adults)
▪ Bowel wall inflammation, edema, tumor, feces, intussusception, stricture, worms
- Non-mechanical (paralytic)

ileus
o Muscles &/or nerves w/ the intestine no longer functioning
▪ Causes → neuromuscular d/o or vascular d/o
- Intussusception
o One segment of intestines telescopes inside of another causing intestinal obstruction
o Rare, MC in kids <3yrs
o The intussusception telescopes into the intussuscipien → drag associated mesentery w/ it
o PATHO→
▪ Invaginated segment carried distally by peristalsis – possible imbalance in longitudinal force of contraction
(infants) or tumor changing normal peristalsis
▪ Mesentery blood & lymph vessels become involved w/ intraluminal loop & are squeezed w/in engulfing
segment
▪ Lead to venous & lymphatic congestion → edema → ischemia → necrosis
o Sign on CT/US → target sign or sausage shaped mass
Celiac disease (gluten sensitive enteropathy)
- Characterized by immune-mediated gluten-induced damage to mucosal villi of small intestine
- Inflammatory immunological intolerance to gluten (gliadin) that does not go away
- Even low amnt of gluten may cause villi histo changes w/o overt clinical symptoms → symptoms can resolve w/in days or wks but
damage WILL RECUR if gluten reintroduced into diet
- Increases risk for GI related cancers

Td
- HISTOLOGY
o Decreased intestinal enterocyte ht
o Villous atrophy
o Crypt hyperplasia (crypt in large or SI)
o Increased intraepithelial T-lymphocytes
o Histology = GOLD STANDARD to dx celiac in adulthood via EGD after + serum tissue tTG-IgA antibody test
- Genetics
o Strong MHC Class II HLA assoc → 35%
▪ HLA-DQ2 (MC)*******
▪ HLA-DQ8 (LC)
o First degree relative that is affected
- Other cont. factors: viral infection (rotavirus) or early life feeding patterns
- PATHO→
o Inappropriate adaptive immune mediated enteropathy caused by permanent sensitivity to gluten in genetically
susceptible pt
o Gliadin-induced autoimmune adaptive immunity CD4 T-cell reaction → T cell recognize gliadin peptide on HLA-
DQ2/8 APC

affair
o After gliadin-induced autoimmune activation of CD4 Tcell → clonal expansion of B-cells & production of
autoantibodies:
▪ Gliadins → IgG & IgA autoantibodies to protein in wheat, rye, and barley
▪ IgA antibody against reticulin CT around smooth muscle fibers (tissue transglutaminase → IgA autoantibody)
- Malabsorption of vitamins D, folic acid, Ca, & iron
o MC extra-intestinal mani is IDA
o Preferentially absorbed through proximal small intestine (esp. iron)
o Vitamins A, E, K also affected the longer condition cont
- Link b/w consumption of ultra processed food & higher levels of cellular oxidative stress & proinflammatory cytokines
o Several of these nutrient issues occur due to food choices on a GF diet (low fiber and high fat intake)
- LC deficiencies
o Thiamine (B1), pyridoxine (B6), and cobalamin (B12) → def may occur
o Mg, Cu, Zn, Selenium, & other minerals → can be low based on dz severity & diet
Inflammatory bowel disease
 - Heterogenous group of disorders characterized by various forms of chronic mucosal &/or transmural inflammation of the
intestine w/ abnormal immune response.
- Combination of env factors & genetic risk
- Two major (distinct) chronic inflammatory d/o’s:
CARD o Crohn’s disease – transmural (all layers) inflammation ****
▪ Majority in terminal ileum & proximal colon (r side), can affect entire GIT (from mouth to anus & also may
inflame Peyer patches)

Ghihesivion ▪
▪
Chronic inflammation process of thickening of bowel wall; can cause narrowing of the lumen
Due to:

[Link]
• Inherited CARD15 gene
o Three mutations on the CARD15 gene on chromosome 16 are assoc w/ some forms of
Crohn’s
o Prevent innate immunity, esp monocytes, from balancing resistance to the microbes in
gut → lead to uncontrolled inflammation & mucosal damage
• Autoimmune response (immune def) – dominant CD4 Th1 reaction induced
• Environmental factors – smoking, diet, infection, NSAIDs

mannitor o Ulcerative colitis – chronic mucosal inflammation

▪ MC in colon/rectum

Gongaemon
▪ Ulcers form where inflammation has limited the function of the cells that line the colon (mucosal layer
epithelial cells)→limited to the mucosal layer of the colon***
▪ Microscopic appearance:
• Inflammation is restricted to mucosa – active inflammation correlated w/ severity of symptoms
• Active phase → neutrophils activate
• Chronic phase → crypt atrophy & distortion
Irritable Bowel Syndrome (IBS)
- Functional bowel syndrome; spastic colon
- Alteration of bowel habits in absence of any detectable/organic cause → exact cause still unknown
o *Serotonin dysregulation*, visceral hypersensitivity*, GI motor disturbances*, bacterial overgrowth, brain-gut
interaction (central dysreg), genetic contribution, food sensitivity
- Subtypes: IBS-C or D or mixed
Neoplasm of SI
- Benign & malignant neoplasms are possible through the intestines
o Malignancy in small intestine = rare
- MC malignant forms of intestines (both more likely >60yrs)
o Adenocarcinoma
NEneum
amviform
▪ MC located in duodenum of SI (lots dump into the duodenum which increase risk)
▪ Most arise from benign adenoma

I
▪ Crohn’s dz inc risk
▪ Adenomatous polyposis syndrome increases risk of malignancy in both the small & large intestine
o NET – more common location in the ileum of SI
▪ Very small → secretes lots of hormones in excess (gastrin, etc)
Adenocarcinoma SI
- Loss of adenomatous polyposis coli (APC) gene (5q21) → thought to be first hit
- APC mutation can be inherited (^ apc)

mÑnFE fregen
- APC mutation can result from somatic mutations (occur spontaneously)
- Mutations of 3 more genes = adenoma → adenocarcinoma
o KRAS + SMAD + TP53
Adenomatous polyposis syndrome
KRAS smAd rp53
- Familial adenomatous polyposis = inherited
- Altered adenomatous polyposis coli gene (APC)
o Lead to multiple adenomatous polyps (adenoma)

aethtance ▪
▪
Germline inactivation of APC gene can also occur in intestines
APC member of Wnt/beta-catenin signaling pthwy (dysfn of cell-cell adhesion & abnormalities in DNA

Apdhvarion
mismatch repair)
o Adenomatous polyposis syndrome increases risk of malignancy in both small & large intestines
▪ More rapid turnover of cells in SI may play role in decreased incidence of SI adenocarcinoma compared to
colon adenocarcinoma
Adenomatous vs inflammatory
- Adenomatous → high likelihood of becoming NEOPLASTIC-INVASIVE carcinoma → adenomatous polyps need screening
- Inflammatory→ low likelihood of becoming neoplastic
Fistula: decreased SA
- Fistula allows luminal contents to bypass considerable small bowel mucosa
Constipation
- Disorder of movement of stool through colon &/or rectum
- IBS-C (irritable bowel syndrome w/ constipation)
o Chronic functional GI d/o
o PATHO→ Serotonin + its receptors
▪ NT of enteric nervous (splanchnic) system → 5HT helps control GI motility, sensations & secretion
• Plasma [ ] reduced w/ IBS-C & elevated w/ IBS-D
▪ Altered GI motility ***
▪ Visceral hypersensitivity***
▪ Post infectious reactivity, brain gut intrxn, alteration fecal microflora, bacterial overgrowth, food sensitivity,
COH malabsorption, & intestinal inflamm
- Functional defection disorders
o Dysynergic defecation (or pelvic floor dyssynergia) – inability to coordinate the abdominal & pelvic floor muscles
▪ 3 phenotypes:
• High anal sphincter pressure at rest
• Inadequate propulsive force
• Hybrid of both
▪ Lead to chronic constipation
- Slow transit
o Myopathy → motility decreases; pelvic floor/anal sphincter dysfunction
o Neuropathy → loss of sensory function; pelvic floor/anal sphincter dysfunction
o Idiopathic
- Secondary
o Metabolic → hypercalcemia, hypothyroidism
o Medications→ opiates, CCB, antipsychotics
o Neurological d/o’s → Parkinson’s, spinal cord injury, DM
o Colonic d/o’s → stricture, cancer, fissures
Fecal impaction
- Can result in chronic constipation (prolonged retention)
- Impaction results largely from persons inability to sense & respond to the presence of stool in the rectum
- Other causes → Immobility, dysregulation of nervous system, & medications (anticholinergic, narcotics)
Diverticular disease of the colon
- Diverticulum→ sac/pouch-like protrusion of a weakened area of the colonic muscular wall
- Diverticulosis→ describes the presence of diverticulum
- True diverticulum → contain ALL LAYERS of GI wall
o Mucosal layer → serosal layer
Diverticulitis = inflammation of diverticula
- Small % of diverticula become inflamed or experience a small tear leading to this
- PATHO→
o Inflamm of diverticulum occurs when thinning & breakdown of the diverticular wall
o May be caused by increased pressure within the colon or by hardened particles of stool, which become lodged w/in
diverticulum
o Large tear can lead to stool leakage into abdominal cavity → infxn (abscess) or inflammation in abdomen → peritonitis
Gas producing foods
- Beans, cabbage, legumes (pea, pnut, soybeans), cauliflower, broccoli, lentils, Brussels, raisins, onions, & bagels
Colon cancer vs colorectal cancer
- Colon cancer
o Screening is important (often asymptomatic)
o Can occur in different parts of the colon → ascending, transverse, descending, & sigmoid colon
- Colorectal cancer (higher chance of death, colon & rectum)
o Patho of progression of an adenomatous polyp → malignancy
o 3rd leading cause of cancer death in US
Colorectal carcinoma sequence

KRAS SMADTYPES
- Loss of APC gene → APC mutation can be inherited or as result of somatic mutations (spontaneous)
- APC/beta catenin plays role in regulation/coordination of cell-cell adhesion & DNA repair

LoseA PE
- Mutation of 3+ genes = adenoma formation → KRAS + SMAD (reg cell dev & growth) + TP53
Hirschsprung’s Dz (aganglionic megacolon)
- Neurogenic form of intestinal obstruction
 endothelin mesenteric submucosal plexus
- Absence of ganglion cells in myenteric & submucosal plexus

pay o Submucosal plexus → ACh→ within the submucosa layer → secretion for motility

HRSPÑʰ
o Muscularlis externa = two smooth muscle layers → b/w is the plexus (anywhere there is smooth muscle in the GI, can
communicate backwards and forwards in GI)
- Failure in relaxation of internal anal sphincter & affected bowel
- Upstream bowel becomes dilated 2ndary to functional obstruction
- PATHO→
o Chromosome 10
o RET protooncogene – RET protein interacts with growth factors & helps cell to grow appropriately
o Endothelin B gene
Toxic megacolon
- Colitis w/ neurogenic loss of motor control
-
- Hirschsprung’s &/or UC can lead to → toxic megacolon Hirsprungorno
Colon dilation → best seen in traverse colon, can affect whole colon
megacolva
- LIFE THREATENING*****
Hemorrhoids
- Arise from a plexus of dilated veins arising from the superior & inferior hemorrhoidal veins
- INTERNAL hemorrhoidal plexus → superior rectal v. drain → inferior mesentery veins (ABOVE pectinate)
- EXTERNAL hemorrhoidal plexus → inferior rectal v. drains → internal iliac v (BELOW pectinate)
- Vessels in submucosal layer in lower rectum
Anal fissure
- Typically, a tear in anoderm (epithelium lining anal canal) BELOW mucocutaneous junction (pectinate/dentate line)
- BENIGN
- Sensitive area to microtrauma → thus area dmg 2ndary to anal trauma from constipation or diarrhea
- Can form a tear w/ repetitive trauma or increased pressure
Anorectal fistula
- Abnormal communication (tracts) running outward from anorectal lumen
o Communications that connect two epithelial lined organs
- Tunnel that connects from inside the anus to somewhere through the skin around the anus
- Locations→ intestine
o Enterovesical – to urinary bladder
o Enterocutaneous – to skin
o Enteroenteric – to intestine
o Enterovaginal – to vagina
- +/- abscess
Anorectal abscess
- Pus-filled cavity in the anus &/or rectum → caused by bacteria invading a mucus secreting gland
- Area is rich in bacteria NORMALLY but internal sphincter acts as BARRIER
- Even w/ proper tx → abscess can lead to formation of an anorectal fistula
BMS 8.23
Ischemia Bowel Disease
- Any process that reduces intestinal blood flow
- Any process that reduces blood flow towards or away from small intestine &/or colon
o Arterial/venous occlusions or arterial vasospasms (nonocclusive mesenteric ischemia)
- Segment of intestine affected:
o Small bowel (small intestine) → mesenteric ischemia
o Large bowel (colon) → colonic ischemia
o Splanchnic (visceral) ischemia → intestine, liver, spleen & kidney
Acute mesenteric ischemia
- Inadequate blood flow (hypoperfusion) through the mesenteric vessels w/ acute onset
- Results in →
o Mucosal barrier disruption
o Bacteria/toxins/vasoactive substances released into systemic circulation
o Cyanotic tissue → bowel necrosis (8-12 hrs)
- Severity of injury related to →
o # of vessels involved
o Amnt of collateral circulation – organs usu compensate for a while w/ limited oxygenation
▪ arterial blood flow from SMA or IMA → less successful in venous system
o duration of ischemia
o systemic mean BP
 - PATHO→
o Thrombotic or embolic arterial occlusion
▪ Decreased/ lack of oxygenation and nutrients in area after occlusion → ischemia lead to ROS (dmg more
tissues, worse in arterial occlusions)
▪ MC occlusion w/in superior mesenteric artery
▪ Emboli commonly 2ndary to cardiac event
▪ Thrombosis MC due to atherosclerosis
o Thrombotic or embolic venous occlusion
▪ Static blood leads to increase in blood volume due to decrease in blood flow past occlusion in area B4
occlusion
• Hydrostatic pressure inc at level of capillaries → inc filtration → edema (worse in venous occlusion)
• w/ edema→ decrease in blood volume & bowel systemic arterial hypotension leading to arterial
ischemia
▪ MC occlusion w/in superior mesenteric vein
▪ Thrombosis often 2ndary to coagulopathy
Chronic mesenteric ischemia
- PATHO→
o Occurs more gradually w/ episodic intestinal hypoperfusion
o MC → diffuse atherosclerotic dz leads to decreased blood flow to tissue (episodic)
o Celiac a. compression syndrome → external compression of celiac trunk by median arcuate ligament or celiac ganglion
- Findings on CT→
o Thickening of intestine wall → ischemia = edema → infection/inflammation