GI Flashcards
Layers of GI
-Epithelium thrown into folds
-muscularis mucosa
-submucosa
-submucoasl pplexus
-Circular
Myenteric plexus
longitudinal
serosa
PANS
Vagal is a mixed nerve and supplies the mid and foregut
- Hindgut is supplied by pelvic nerves
- release Ach and active peptides (VIP and substance P)
- Synapse on enteric nervous system in two plexuses and modulates action
- Vasovagal responses and reflexes
SANS
short presynaptic and long postynaptic
- Celiac
- Superior Mesenteric
- Inferior Mesenteric
- Hypogastic (supplies GU for sexual response)
- Sensory and motor
Enteric
Intrinsic and can funtion in the absence of the other two
- Plexuses
- Also gets input from local receptors
Omphalocele
- Gut contents fail to return to gut after they extend into yolk sac through vitelling duct
- Covered by peritoneum
- Surgical Repair
- Commonly see elevated AFP on triple screen
- Can be associated with Beckwith Wiederman and other congenital anomalies
- Midline
Gastroschesis
- Failure of the lateral body folds to close, often associated with vascular injury during birth
- There will be no peritoneum covering gut contents
- Elevated AFP
- Occurs lateral to the umbilicus
Malrotations
Most commonly involves the cecum being located in the RUQ
- Adhesions that attempt to make it go secondarily retroperitoneal lead to LADD bands that compress duodenum
- Lad bands cause bilious vommiting
- Also can be a nidus for volvulus
Midgut Volvulus
- Winding of midgut around SMA leading to compresssion and ischemia
- Bilious vommiting and necrosis of bowel
- Necrosis with widespread air fluid levels in the bowel
Duodenal Atresia
- Failure to recanalize duodenum after endodermal proliferation
- Highly associated with Downs
- Bilious Vomitting and may present with polyydramnios from impaired swallowing
- Can also be non billious depending on location
- Associated with other defects
Pyloric Stenosis
Hypertrophy of pyloric sphincter that leads to inability to empty stomach
- Palpable olive commonly
- Nonbillious vommiting
- Polyhydramnios
- Seen more commonly in firstborn males
Pancreatic Divism
- Normally ventral bud migrates around to the back and joins with dorsal bud
- Most of organ is in the dorsal bud, but the main pancreatic duct is in the ventral bud
- Divisim can be assymptomatic or can lead to stenosis of the accessory duct and pancretittis
- Also, malrotation can lead to annular pancreas that compresses duodenum
TE fistula
- Esophagus ends in blind pouch and then fistualizes with traches
- Cyanosis, bubbling, and drooling at birth
- Emergency, risk of aspiration pneumonia and cyanosis
- Will also see air int he stomach
Arcuate Line
- Location where the transversalis fascia goes from passing posterior to passing anterior of the rectus
- Location where epigastrics enter rectus
Inguinal Canal
- Deep Ring is lateral to epigastrics and is formed with transversalis fascia
- Internal oblique forms the cremaster
- External oblique forms the superficial ring that is medial to the epigastrics
Femoral Canal
Inferior to inguinal ligament
- Contains femoral sheath with artery and vein (vein being medial) (venous by penis)
- Nerve passes laterally and outside of sheath
- Lymphatics and saphenous pierce
Retroperitoneal
- 2 (Descending), 3 transverse, and 4 (ascending) duodenum
- Head, body of pancreas
- rectum, ascending and descending colon
Intraperitoneal
1st duodenum (bulb)
tail of pancreas
Sigmoid (redundant mesentery that is liable to volvulus)
Lesser Sac
-Epiploi foramen that contain the common bile duct, portal vein, and hepatic artery
Lateral Hypothalamus
- Causes hunger and food seeking behaviors
- Is inhibited by leptin
- Destuction leads to apathy and anorexia
DM hypothalamus
- Causes satiety
- Destruction leads to aggression and hyperphagia
- Leptin stimulates
Salivary Glands
Stimulated by PANS (watery) and SANS (Viscous)
-Flow rate determines ioinic conentation
-Higher flow is more hypertonic
-Lower flow is mor hypotonic
-Major regualation by absortion of Na
-HCO3 is constant and rich in hypotonic souatin
-Normally Cl and Bicarb predominate
-Lipase can digest through stomah
-Amylase can’t
-CN7 controls submandibular (seromucous) and sublingual (mucous)
CN9 does parotid (serrous)
Esophagus
Superior is skeletal muscle from 4th pharyngeal pouch contraolled by vagus at ambiguus
- Inferior is smooth muscle controlled by vagus and dorsal motor 10
- Squamous epithelium
Swallowing
- Esophagus has negative rpessure, UES prevents air and LES prevents gastric
- Primary peristalsis is from overiding vagal
- Secondary is local reflex archs
- Retching is vomitting against closed UES so food returns to stomach
Stomach Anatomy
- Fundus is superior (Short gastrics)
- Cardia
- Body (Parietal and Chief Cells)
- Antrum: Mucous Cells and G Cells
Digestions
- Intrinsic rate is determined by interstitial cells of cajal
- MMC (motilin) causes contraction every 90-120 mins
- Cephalic phase is mediated by the vagus nerve
- Gastic Phase is mediated by stomach distension
- Intestinal phase is mediated by amino acids, chyme in intestine
Parietal Cells
- CA produces H and HCO3
- The H is exchanged with H/K exchangers and HCO3 is sent into blood (To keep electroneutrality, Cl is sent into stomach with H)
Parietal Cell Stimulation
- Vagal stimultion via Gq M3
- Gastrin Stumlation via Gq (released from G cells in antrum and dudodenal cells)
- H2 works through Gs
- PG and somatostatin are Gi
Receptive relaxation
-Dilation of body and fundus to receive food, mediated by vagal and CCK
Gastrin
- Released in response to distension of stomach and peptides in GI
- Inhibited by GIP
- Also inhibited by secretin, VIP, and somatostatin
Absorption
Can absorb alcohol and aspirin (weak acid is protonated in GI and can traverse membranes) -Treat overdose with HCO3 to trap in tubule
Duodenum
1st: peritoneal, duodenal ulcer may bleed though gastroduodenal
2nd: AMpula of vater. Mid and foregut difference
3: Crosses midline, SMA goes over (SMA syndrome)
4: Ascending, ligament of trietz
Brunner GLands
Intestinal glands that secete a heavily alkaline mixture
Paneth
Innate immunity, protect stem cells in crypts
Fe
Fe 2+ in duodenum. Put there by vitamin C
Folate
Jejunum
B12
terminal ileum (IF receptors)
CCK
I Cells: Stimulates receptive relaxation, increases gallbladder contraction and pancreatic secretions
-Slows gastric emptying
Secretin
S Cells
-Trophic for panreas, HCO3
GIP
K Cells inhibits gastrin and stimulates insulin
Motilin
ECL cells
VIP
Released from vagus
- Motility and increased Secretions from intestine
- decreases gastin
Colonc
Site of bacterial fermentation that generates vitamin K
Can secrete K and HCO3
-There is no MMC in colon
-1-3 times per day there is a large mass movement that propels food into rectum to initiate the recto-defecation reflex
Exocrine Pancreas
Stimulated by secretin, CCK, Vagal
Secretes inactive precursors that are activated by trypsin
-Typrsinogen is activated by enterokinase (only necessary peptidase)
Liver
Hepatocytes: Zone 1 is periportal and zone 3 is perivenous (Centrilobular)
Bilirubin
- Transported back to blood via a Na/Bile transporter
- Heme is converted to water soluble biliverdin in tissues by heme oxygenase
- Biliverdin is then converted to bilirubin by biliverdin hydroxylase and transported on albumin to hepatocytes
- Carrier mediated entry into hepatocytes where in the ER it is conjugated to glucuronide to be secreted
- Secreted in bile
- Oxidized by intestinal bacteria to urobilinogen. majoirty is excreted as sterobilin in the feces, 10% is resorbed and secrteted as urobilin in the urine
Bile
Cholesterol is made into cholesterol acids where it is then conjugated to taurine and glycine to make watersolube/ amphipathic
Then sent through biliary ducts to be stored in gallbladder
-Gallbladder has columnar epithelium that concentrates (Na/K ATPase) and secretes in response to vagal and CCK. Inhibited by somatostatin
-Emulsifies fats, needs to work with co-lipase and then resorbed in the terminal ileum 95%
Mouth Lesions
Lichen Planus
- Oral Candidiasis scaping off will cause bleeding, but can be scraped off
- Hairy Oral Leukoplakia: EBV, lateral tongue, can’t be scraped off
- Leukoplakia: Precursor to SCC
- SCC associated with smoking and alcohol
- Melanoma also a possible cancer
Salivary Tumors
- Warthins: Associated with smoking: Lymphocytic infiltrate that forms germinal centers. Good prognosis, but can recur
- Pleiomoprhic Adenoma: Multiple cell types but usually include cartillage. Good prognosis and is benign, but may recur
- Mucoepidermoid: Mucinous cells that stain with mucous stains. Malignant and worse prognosis of them all. May be painful because of involvment of the facial nerve
Infections
- S ureus is the most common
- Mumps also causes parotiditis
Sjogrens
-Causes dry eyes and dry mouth
SS-A/B Ro/La
Can cross placenta and cause heart block in neonate
Esophageal diverticula
-Zenkers is the most common, and occurs above the cricopharyngeous which is inferior pharyngeal constrictor, below thyopharyngeus. UES is same as inferior pharyngeal constrictor
False diverticulum which is a pulsion diverticulum with only the mucosa protruding through
-Can be false near LES or true midesophageus (associated with TB or chronic inflammation
Achalasia
- Loss of myenteric plexus is key inciting event
- Can be congenital or secondary to Chagas Disease
- Scleroderma also causes a similiar picture
- Loss of VIP and NO from vagal inputs to myenteric plexus
- Low tone above LES and high tone at LES, but LES is usually normal
- Risk factor for SCC because of inflammation
- Inability to swallow solids or liquids
- May also be secondary to cancer, TB, sarcoidosis
GERD
- Loss of LES tone and increase in pressure (Pregnancy, obesity) leads to reflux of gastric contents
- Pain, cough, and adult onset asthma is a risk for intestinal metaplasia
Barrett’s
Intestinal metaplasia of esophagus secondary to chronic inflammatoin from GERD
- Bile acids may play a role
- Eosinophils will be present as well as basal layer hypertrophy and increased size of papillary projections
- HerbB2 +
Adenocarcinoma
-Occurs in distal 1/3 of esophagus and is associated with Barrett’s as are risk factors
Squamous Cell Carcinoma
- Associated with inflammation and occurs in upper 1/3
- Achalashia, Zenkers, Chemical ingestion, infections, Smoking, alcohol, hot drinks
- Both cancers tend to spread locally and have a poor prognosis
Esophageal Infection
- Generally occurs in the context of immunodeficecny
- Candida causes a white membrane
- CMV causes linear ulcerations and HSV causes punched out ulcerations
Esophageal Varicies
- Portal hypertension leads to dilation of left gastric vein and portocaval anastamoses
- Bleeding occurs in lower 1/3 of esophagus
- Treat with vasopressin and octreotide acutely and beta blockers for prophylaxis
Mallor Wies
- Linear tear in mucosa leading to hematemasis
- Occurs at the GE junction
- Boorhaves is a full thickness tear that can be associated with pneumomediastinum and is an emergency
Esophageal Strictures
- Can be from chemical ingestion or benign grwoth
- Will be inability to swallow solids, but liquids will be fine
Plummer Vinson Syndrome
- Severe Fe deficency anemia (konilocytosis)
- Esophageal strictures
- Glossitis
- Seen in post menopausal women or in celiacs sprue (fe absorbed from duodenum)
Hital Hernia
- Sliding is most common and is associated with increased risk of GERD
- Paraesophageal is less common but can cause strangulation
Acute Gastritis
-Loss of mucosal barrier or increased acid production leads to ulceration
-NSAID’s loss of PGE1
-H Pylori
-Alcohol
Cushings: TBI leads to increased vagal and increased Ach
-Curlings: Burns leads to hypovolemia leading to sloughing of mucosa. All patietns in ICU are on PPI
-Stress
-Uremia
-Treat with PPI, can give misoprostol to replenish PGE is patients are on NSAIDs
Eicosanoid Pathway
- AA
- HTBE converts to leukotrienes
- COX 1 and 2 convert to PGH
- H then converted to E and D ( E is implicated in gastritis)
- H to I
- H to TXA2
Chronic Type A
Autoimmune Gastritis
- Predominantyl involves the body and the fundus (no parietal cells in the antrum)
- Autoantibodies to parietal cells (IF or H/K ATPas)
- Leads to achlorhydria, loss of IF and pernicous Anemia, increase risk for adenocarcinoma
- Gastrin levels will be elevated because of inabilty to produce H
Chronic B
- H Pylori
- Leads to loss of mucosal protection
- Primarily involves the antrum and lesser curvature
- Treat with erradication of H pylori
- Increased risk for intestinal type adenocarcinoma
Mentrier Disease
- Unknown cause leads to hyperplasia of mucous cells
- Leads to protein losing enteropahty
- Achlorhydria
- Increased risk of gastric cancer
- Rugal hypertrophy is characteristic lesion
Gastric Peptic Ulcers
- Well demarcated boundaries
- Cause by NSAID’s of H Pylori (all things that can lead to gastritis)
- Decreased Gastric acid secretion. Pain with meals leading to N/V and weight loss
- Increase risk for intestinal type gastic cancer
- Majority are located in antrum and lesser curvature
- Close to left gastric artery and may perforate and cause bleeding
Duodenal Ulcers
- Almost all are caused by H pylori, some ZE syndrome
- Increased acid production.
- Pain is less after meals
- Malignant transformation is rare, but perforation and bleeding into gastroduodenal is possible
Zollinger Ellison
Gastrin secreting tumor of the pancreas that leads to hypertrophy of parietal cells and increased gastric acid secretion
- Think of MEN1 if see this (Pancreas, Pituitary, PTH)
- G cells will be atrophied in antrum and parietal cells will be hyperplasia in fundus and body
Intestinal Type Adenocarcinoma
- Most common and seen in older patients
- Will present as an ulcerated appearing lesion with not clean edges
- Risk factors: Nitrosamines, H pylori and chronic gastritis, achlorhydria (Mentrieres)
- Commonly follows intestinal metaplasia and is commonly seen in the lesser curvature and antrum
- Increased risk with FAP mutaion
Diffuse Type
- More commonly occurs in younger patients and is not related to H pylori
- Signet ring cells, Krukenberg tumor
- OFten causes desmoplastic proliferation leading to linitis plastica and a thickened stomach
Gastric Cancer
Very common and second leading cause of death worldwide
- Spread to lymph nodes
- Sister Mary Joseph is periumbilical that causes umbilical protrusion
- Virchow’s node is left supraclavicular
- Kruckenberg is with diffuse type
Celiacs Sprue
- DR2 and 8. Autoimmune disease to gliadin. Positive for endomysial, tissue transglutaminase, gliadin. Accumulation of lymphocytes in lamina propria
- Involves the distal duodenum and proximal jejunum with major pathology in the jejunum
- Presents with diahhrea and failure to thrive with several vitamin deficencies
- Associated with dermatitis herpetiformis on the extensor surfaces
- Removal of gluten from diet is currative
- Increased risk for T cell lymphoma
Disacharidase deficency
- Most commonly lactose, often is genetic but can be acquired and appear after a viral illness or diahrrea
- Osmotic diahrrea with normal vili
Whipples Disease
- Infection with gram positive microrganism that leads to PAS positive macrophages in lamina propria that leads to malabsorption
- Presents with other problems including constitutional, migrating polyarhalgias, heart and neurologic dysfunction
- Treat with TMP/SMX
Tropic Sprue
Similiar to whipples although no microrganism ID
- Treat with tetracyclines
- Appears simlar to ciliac on microscopy with blunting of vili
Abetalipoproteinemia
- Loss of production of B-48 and B-100. 48 can’t make chylomicrons leading to fat engorged enterocytes. 100 can’t make VLDL leading to engorged liver
- Associated with fat soluble vitamin deficencies and normally presents in kids with acanthosis, eye problems and vision loss, and ataxia
Lymphectasia
-portal HTN and scites lead to impaired lymph function
Pancreatic Insufficency
- Chronic pancretitis, CF, or cancer
- Malabsorption of fat soluble vitamins
Divertiula
- Most are caused by pulsion forces and more commonly effect the distal large intestin arround the sigmoid colon
- False divertiuculum with the submucose and mucosa protruding through the muscularis externa
- True (Meckels)
Meckels
- True diverticula
- Can cause volvulus and intususeption. can also be a sight of ectopic gastric and pancreatic tissue that leads to ulceration and bleeding
- Differentiate from omphalomesenteric cyst
Diverticulosis
-Infectino and inflammation of diverticul, most commonly due to fecolith
-Causes left sided appendicitis with leukocytosis, fever, pain
-May perforate and treat with antibiotics
-May fistula with bladder leading to pneumouria
-Most commonly seen in sigmoid colon
Can cause rectal bleeding elading to Fe deficecny anemai
Intuseseption
- Telescoping of bowel segments
- OCcurs most commonly in kids, if adults think of cancer or polyps
- most common at ileocecal valve
- Causes ischemia and leads to pain, currant jelly sputum, and often palpable mass
- Surgical emergency
- Presentation is often 10-20 minutes of severe pain followed by relief and the cycle repeats
Hirschprungs
- Failure of neural crest cells to migrate into both submucosal and myenteric plexus
- Leads to tonic constriciton that always effects rectum and then proximal
- Failure to pass meconium, bilious vomiiting and bowel distension
- Increased risk with downs, wardenberg syndrome and commonly males
- RET oncogene
IBD
- Commonly presents in mid20’s as recurrent abdominal crampy pain and diahrrea
- UC always has blood, crohns only sometimes has blood
- Treat with immunosupressants
- Increased risk for CRC
- Commonly seen with B27 and autoimmune disorders
Crohns Disease
- Transmural destruction leading to fissures and fistulas
- Th1 mediated with the presence of many non casseous granulomas
- Always involves terminal ileum but has skip lesions
- Inflammation and healing leads to fibrosis and creeping fat, also narrows lumen leading to string sign
- Malabsorption and nutritional deficencies are common
- Terminal ileum involvment means decreased B12 absorption and cholesterol absorption
- Increased risk for gallstones because of bile loss
- Increased oxalate absorption leads to kidney stones
- Treat with sulfasalazine, TNF-a inhibitors, and surgery is not currative, but often improves symptoms
- Associated with migratory polyartritis, erythema nodosum, `
Ulcerative Colitis
- Always involves rectum and ascends along distal colon
- Always has bloody diahrrea
- Characterized by TH2 mediated crypt abceses confined to mucosa and submucosa. NO transmurain inflammation
- Pseduopolyps are the characteristic lesion
- Risk of megacolon
- Major increased risk for CRC
- Colectomy is currative, but other treatements are immunosupressants, sulfasalazine
- Lead pipe appearance from loss of haustra
- P-ANCA positive and associated with sclerosing cholangitis and pyoderma gangrenosum
Irritable bowel syndrome
- Changes in fecal frequency and consistency that pain is relieved with defectation
- There is no idetifiable cause. treat symptoms
Appendicitis
- RLQ pain due to inflammation of appendix
- In adults is caused by fecalith
- in kids it is from lymphoid hyperplasia
- Be sure to rule out ectopic pregnancy or diverticular disease in elderly
Pseudomembranous colitis
- C dif releases AB toxins that attract neutrophils and cause actin polymerization leading to pseudomembran
- Usually not invasive and usually not bloody
- Occurs secondary to antibiotics (Clinda, Amicilin)
- Treat with metronidazole or vanco
- Don’t give antidiarrheals, could risk accumulation of toxin and also increased risk of toxic megagolon which is biggest risk
Typhoid Fever
Salmonella Typhi that enters through M cells and can live inside cells and polymerize actin
- Ulcerations of GI, bacteremia and splenomegally
- Classic rose spots on abdomen
- Colonizes gallbladder and becomes able to carrier
Entaemeb histolytica
- Protozoan that caues amebic dysentery
- Invades/burrows into small bowel and colonic mucosa and enters portal system
- Can cause abcesses in liver
- RBC seen ingested
- Flask ulcers where entered
Giardia
- Adheres to small bowel wall and causes malabsorption leading to foul smelling stools
- IgA deficency
- Treat with metronidazole
Meconium Ileus
CF
Necrotizing enterocolitis
- Increased risk with prematurity
- Nerosis of bowel often secondary to bacterial invasion (immature host defenses)
- Risk of perforation and peritonitis
Ischemic Colitis
- Atherosclerosis leads to ichemia and infarciton in watershed zone of large intestine (SMA and IMA) alsong spleni flexure
- Can also occur in the rectum
- Leads to pain with eating and possible necrosis
Adhesions
Most common post surgery
-Most common cause of small bowel blockage
Angiodysplasia
- Dilated blood vessels generally in the right bowel
- Ileum, cecum, and ascending colon
- HHT
- Common cause of hematochezia
Benign Polyps
-Hyperplastic polyps are common and occur most commonly in the rectosigmoid and harbor minimal risk
Juvenile Polpys
- Hamartomas that occur most commonly in the rectum
- Growth of lamina propria
- If sinlge there is little risk of malignancy, if multiple, there is increased risk
Puetz-Hugh-Juegers
- AD
- Nonmalignant hamartomas throughout GI
- ASsociated with hyperigmentation of Mouth, Genitals and hands
- Increased risk of colon cancer and other visceral mlaignancies including thyroid
Adenomatous Polyps
- Occur most commonly in the left colon, Left colon most commonly presents as a mass lesion that obstructs flow
- Right sided more often bleed
- Malignant potetntial a function of architecture
- Tubular is pedunculated with minimal fingerlike projections and is more likely to be benign
- Villous has many vilous like fingerlike projections and carries a much greater risk of malignancy
FAP
- AD mutation in APC on chromomse 5
- APC is a TSG in the beta kaetanin pathway
- Thousands of polyps throughout colon always involvig the rectum
- Will always get colon cancer, and colectomy is often performed
Gardners Syndrome
-AD, loss of FAP leading to increased risk of colon cancer and also an increased risk of a number of soft tissue malignancies including osteomas and pigment changes in the eye
Turcots
- AR Colon cancer and CNS cancer (GBM)
- Only hereditery sydrome that is AR instead of AD
HNPCC
AD
Microsattelite instabilitty
-Increased risk of cancer that more commonly involves the right or proximal colon
CRC Progression
-15% are microsatelite instability
CRC Progression
Majority along the APC tract
- inital mutation in APC (TSG/Beta Kaetenin) leading to the presence of polyps
- Then there is mutation in KRAS that increases the growth of polyps
- THen mutation in P53 and other genes leads to cancer
- COX2 overexpression is a common feature
- DCC (Deleted in colon cncaer is also another common mutatoin)
CRC
-Most commonly involves rectosigmoid and then ascendinga nd descending colon
-Left sided is most commonly a mass lesion that causes obstruction and hematochezia
-RIght sided is ore likely to ause anemia from occult bled
Strep bovis endocarditis is sometimes seen
-Lesions will show apple core or ostructive sions
-CEA is a good marker for progression, but not for screening
Carcinoud Tumor
- Most common tumor of the smal bowel. Generally involves the appendix, illeum, rectum
- Neuroendocrnie cells (S100) leads to release of seretonin
- If confined to GI tract, seretonin will be metabolied
- If malignant (Liver most commonly) seretonin can go systemic and cause seretonin syndrome
- DIahhreas, flushing, and right sided valvular issues
- Seretonin is metabolized by MAO-A in the liver to 5-HIAA
- Treatment is octerotide
Alcohol
AST>ALT, acetylaldehyde is the toxic compound
- Increases NADH to NAD ratio (NAD is cofactor in adehydrogenases)
- Leads to stop of glycolysis and decreased utilation of glucose
Steatosis
- Reversible change with macrovesicular bodies
- NAFLD wil have elevated ALT
- Hep B is ground glass hepatocytes from increased levels of protein expression. HBsAg
- Hep C will show microvesicular change
- Cell death from hep viruses is mediated by CTL response to intracellular virus
Hepatitis
- Painful hepatomegally
- Mallory bodies of ubiquitinated intracellular intermediate filaments
- Microvesicular fatty change
- Swollen and necrotic hepatocytes with neutrophilic infiltrate
- Acetylaldehyde is the main toxic metabolite
Infiltrate
-If viral there will be lymphocytic infiltrate if acoholic there will be neutrophilic infiltrate
Cirrhosis
- FIbrotic sclerosing bands that are laid down by stellate cells that transform into fibroblasts under the influence of tgf-b
- Bands of fibrosis and regnerating cells leads to small nodular liver
- Sclerosis is most prominent around central vein
Cirrhosis
- Liver dysfunctino
- Decreased glucose and albumin and clotting factors
- pHTN and varicies etc (Treat with octerotid)
- Hepatic encephalopathy caused by inability to run urea cycle leads to accumulation of amonia in blood and hepatic encephalopathy (NH3 from bacterial and GI metabolism of dietary AA is sent to liver that can’t keep up with urea cycle. Leads to increased NH3 in blood. Treat with lactulose, which is fermented to an acid that traps NH3 in GI and destresses the urea cycle.)
- Spider angiomata, gnecomastia etc
- Thrombocytopenia can occur because of splenomegally
- Treat hepatic encephalopathy with neomycin (decrese bacteria) and lactulose
Markers of hepatic disease
- ALT is liver specific and AST is in other tissues
- ALP is seen in obstructive liver disease, HCC and biliary tree disorders
- GGT is specific for the liver and can be used to detect alcoholism and ALP for liver origin
Reyes Syndrome
- Aspirin given to child with viral illness results in mitochondrial dysfunction, decreased beta oxidation of fats and microvesicular fatty change
- Also leads a coma and is potentially fata
- Do not give kids with viral illness aspirin (Distinguish with kawasaki)
- Large mitochondria on histology
- Short chain FA will accumulate and cerebral edema is major pathology along with hyperanmmonemia
Hepatocellular Carcioma
-Commonly a consequence of long term cirrhosis
-Can also be caused by aphlatoin from sapergillous
-Leads to hepatic dysfunctoin
Early metastsis via hematogenous spread
-Can Cause Budd Chiari
-EPO is a common neopplastic process
-Elevations in AFP are a marker
Macronodular cirrhsois carries an increased risk
Cavernous Hemangioma
-Highly vascular tumor that is idioathic, don’t biopsy becaues can bleed everywhere
Heptic Adeoma
Associated with OCP and steroid use
- Spontanously regresses after discontinuation
- Hepatic Blastoma can occur in kids
- Focal Nodular Hyperplasia seen in women and not associated with OCP, can ID with elevated tech scan uptake due to presence of kupfer cells
Angiosarcoma
-Associated wtih PVC and arsenic (Lipoic acd inhibitor that stops PDH and alpha ketoglutarate)
Cholangiosarcoma
- Tumor of bile canaliculi epitheliuum
- Often secondary to longstatanding billiary disease, especially primary billiary cirrhosis
- Also increased risk in clonorci infection
Nutmeg Liver
- Central venous congestion leading to hypoxic cell death of central region. Centrolobular necrosis
- Can be a consequece of right heart failure
- Can also be a consequence of budd chiari syndrome
Budd Chiari
- Thrmobosis of the hepatic vein that leads to hepatic parenchymal congestion and also rapid onset of portal hypertension
- Rapid onset of ascites, varicies etc , and SPLenomegally
- Commonly seen in hypercoagulble states, pregnacy, polycythemia, HCC
- Will appear like cardiac cirrhosis but there will be no JVD.
- Can also be form an occlusion of the IVC
- Visible abdominal and neck veins
Alpha one antitrypsin
-Codominant trait that results in misfolded protein that accumulates in the ER of hepatocytes and leads to PAS positivit
-Assocaited with panacinar emphysema
Heterozygotes will be at increased risk and homozygotes will get the trait (codominance)
Indirect Bilirubin
- Hemolysis or impaired Bile formation
- Hemolysis can increase risk of pigmented gall stones
- Or impaired production (HCC)
Direct Bilirubin
- Caused by blockage (Gallstone, parasite)
- Decreased Transport
Physiologic of Newborn
- Relative decrease in action of UDP gluconyl transfase elads to accumulation of indirect bilirunin that is water insoluble and accumulates in BG (Kernicterus)
- Treat with phototherapy to increase solubility
- Same reason for Gray Baby
GIlbert’s Disease
-Genetic decrease in UDP transferase or decrease in uptake of unconjucated bilirubin from bloodstream leads to transient inconsequental jaundice at times of stres
DubinJohnson
- AR defect in MRP-2 that can’t transport conjugated bilirubin into bile duct
- LEads to a grossly black liver, but physiologically inconsequental
- Rotor is a milder syndrome
Criggler Najar
- Type 1 is severe and is a complete lack of UDP transferase, does not respond to phenobarbitol
- Type 2 is paritial that wil cuase sequale, but can be treated with phenobarbitol
- Increase in UCB leads to deposition in brain and kernicteus
Wilsons Disease
- Chromosome 13 AR
- Defect in ATB7 that leads to a loss of Cu loading and increase in serum free copper, also impairs Cu excretion in Bile
- Decreased cerruloplasmin and increased Cu
- Deposition in BRain (BG causing dementia and parkinsons)
- Cornea, Joints
- Liver Causing Cirrhosis
- Treat with penicilamine
Hemochromatosis
- AR associated with HLA A-3
- HFE mutation leading to increased Fe absorption that is not regulated
- Fe deposits in tissues as hemosderin leading to hemosiderosis, diseaese is hemochromatosis
- Elevated Ferretin, Fe, Decreased TIBC and icnrease saturation
- Acuumlates in Pancreas (DM1), Joints, Testes, LIver, SKin leading to increased melanin
- Also deposits in heart leading to heart filaure
- Treatment is phlebotomy or defuroamin
- Can be secondary to chronic transfusions
- PResentsearlire in men because women lose iron in menses
Secondary Billiary Cirrhosis
- Backup of bile intraheatically leads to cirrhosis
- Classic presentation is elevated cholesterol, ALK P, Direct Bilirubin
- Also see pain, pruritis, Jaundice, pale stool (no stercobilinogen)
- Can be a nidus for ascening cholangitis
Primary Billiary Cirrhosis
- Autoimmune disease detected by elevated anti mitochodrial Ab
- ALso associated wit elevated IgM (Cryoglobulin), seen in patietns with other autoimmune disease (middle aged women)
- PResentation of elevated cholesterol, direct bilirubni, and alk P (May also be elevated late in pregnancy)
- Lymphocytic infiltrate with granuloma formatoin
Primary Sclerosing Cholangitis
- Unkown mechanism causing alternating fibrosis and ectasia of bile duct
- Associated with IBD and P-ANCA
- Can lead to secondary Billiary Cirrhosis
- Can also see hypergammaglobulin with elevated IgM and cryoglobulinemia
Cholelithiasis
- If there is an imbalnace in the ratio of bile acids to chilesterol or bilirubin stones will form. Generaly, a decrease in bile production leads to bad balance
- Choleserol are radioopaque and most common, althoruhg mied have same presnttion and are even mroe common
- Pigmented occurs with hemolysis, cirrhosis or infection
- Black is from elevated conjugated bilirubin
- Brow is from infecctoin
- Can cause inflammation and cholecystitis
- Can cause blockage leading to colic and if block ble duct lead to pancreatitis or pancreatic insufficency
- Can also serve as a nidus for ascending cholangitis
- Can form fistula with small intestine and lead to gall stone illeus that is stuck on the illeocecal valve with the presence of air in the gallbladder
- Biliary sludge is a complication of CF, rapid weight loss and perenteral nutrition
- Increased risk with estrogen (Women fat, fertile) estrogen increases LDL receptor on heps and increases cholesterol concenratino
- Native AMerican, overweitht, CF, Clofibrates
- Rockitoff Antsky bodies occur when there is blockage that leads to diverticula in the gallbladder
- Longstanding can lead to porcelin gallbladder, calcification and increased risk for gallbladder carcinoma
Cholecystitis
- INflammation of the gallbladder generally secondary to gallstones
- Fever, RUQ pain, Jaundice
- Ascendign cholangitis can also be a cause
- Increase in Alk Phos that is released from billiary tract
Acute Pancreatitis
- Ethanol, Hypercalcemia, hypertriglyceridemia, trauma, CF, gallstones, steroids, mumps, autoimmune
- Elevations in amylase and lipase
- EPigastric pain that radiates to the back
- Soponification and fat necrosis taht leads to hypocalcemia
- Can also lead to ARDS and DIC
- Pseudocyst formation which is a cyst that is lined by granulation tisse that can ruptture and lead to massive hemorrhage
Chronic Pancreatitis
- Most commonly due to multiple bouts of acute
- CF alcohol are common causes
- Pancreas will become calcified and dysfunctional with often and dilated duct
- Dysfunctionl pancrease leads to malabsorption and fat soluble vitamin deficency
- CAN lead to new onset DM1
- Risk factor for andenocarcinoma of the pancreas
Pancreatic Adenocarcioma
-Tumor of the pancreatic epithelium
Most commonly arises in the head of the pancreas
-Risk factors are age, smoking, chronic pancratitis,
-Tumor marker is CA-19-9 and can be CEA, but not as specific
-Pain radiates to back, and often presents with signs and symptoms similiar to acute pancreatitis
-Commonly causes galbladder obstruction resulting in a dilated and palpable gallbladder
-Can also cause torsseaus sign of migrating thrombophlebitis that is painful
-Can be a cause of aeseptic endocarditis
-Poor prognosis
