Miscelania Flashcards
Where are AAs and monosaccharides absorbed?
Duodenum and Jejunum
Where are Cobalamine (B12) and bile salts/acids absorbed?
ileum
cells of Cajal
regulate electrical signals, can influence amplitude, but not frequency. Use Ca and K
enterochromaffin cells
use 5HT to signal myenteric plexus about the gut situation
parasympathetic and sympathetic
- Parasympathetic: mostly cholinergic of vagus nerve; stimulates activity of the enteric plexuses, increases GI motility and secretory activity.
- Sympathetic: mostly adrenergic, generally inhibits activity of the enteric plexuses, decreases GI motility, contracts GI sphincters, constricts GI microvasculature
Acetylcholine
primary excitatory transmitter from sensory cells and from motoneurons to muscle, epithelium, secretory cells and at interneuronal junctions. increases intracellular Ca++
Gastrin releasing peptide
released from vagal nerve endings to stimulate G cell secretion of gastrin.
Substance P
(tachykinin) - an excitatory transmitter generally co-released with acetylcholine.
Vasoactive Intestinal Peptide
(VIP) – Promotes motility
Relaxes smooth muscle in esophagus and stomach
Stimulates fluid secretion and promotes dilation of the GI vasculature. increases cAMP
Nitric Oxide
an inhibitory transmitter co-release with VIP from inhibitory motoneurons, hydrophobic- intracellular targets.
Gastrin
Gastrin – G cells in antrum of stomach detect amino acids leading to pepsinogen and H+ release by parietal cells.
Cholecystokinin (CCK)
I cells in D/J detect fat and amino acids, secretion of pancreatic enzymes and bile salts involved in fat uptake
Secretin
S cells primarily in D/J detect acid stimulates secretion of pancreatic juice including bicarbonate and inhibits gastric motility.
Gastric Inhibitory Peptide or Glucose-Dependent Insulinotropic Peptide (GIP)
K cells in D/J detect carbohydrates and fat to inhibit gastric acid secretion and stimulate insulin release from pancreas.
Motilin
secreted by endocrine cells; released cyclically during fasting state to initiate Migrating Motor Complex
respiratory quotient
CO2/02
Fat has the lowest RQ, Carbs the highest
Protein metabolism
1g protein= 6L O2 and 4.8L CO2
Nerve influences on saliva
Parasympathetic (glossopharyngeal and facial): acts through VIP and acetylcholine on muscarinic receptors to increase secretion of watery saliva.
Sympathetic (cervical sympathetic chain) acts through norepinephrine on β1- and α1 adrenergic receptors to secretion of viscous saliva
Xerostomia
subjective sensation of dryness of the oral mucosa
alpha and beta pancreatic cells
beta release insulin, alpha release glucagon (in response to high protein levels)
Intestinal epithelial cells
Convert glutamine, glutamate and aspartate from the diet to a-ketoglutarate.
Colonocytes
Use short chain fatty acids produced by gut bacteria.
glucagon receptor binding
Ligand binding causes activation of adenylate cyclase, production of cAMP, and activation of PKA
PKA activation in hepatocyte:
Glycogen synthase is phosphorylated and inactive.
Glycogen phosphorylase kinase is phosphorylated and active.
Glycogen phosphorylase is phosphorylated and active.
gluconeogenesis chemistry
The ATP to power gluconeogenesis comes from the FAD(2H) and NADH reduced by fatty acid beta oxidation.
The acetyl CoA produced by fatty acid beta oxidation is a substrate for ketone body synthesis.
muscle and fasting
Skeletal muscle
Proteolysis produces free amino acids. Branched chain amino acids are used by the muscle as fuel. Alanine and glutamine are exported for use as gluconeogenic substrates by the liver.
As the fast prolongs, skeletal muscle can use ketone bodies for energy.
Cardiac muscle
Fatty acid beta oxidation increases; glycolysis decreases.
Hypercatabolism chemistry
Lots of catecholamines for the first day, then they decrease sharply, glucagon spikes immediately, slowly peters off, cortisol slowly increases over a day or so
Amylase
Amylase activity is highest in the duodenum.
Amylase is an endoglycosidase. It cuts a-1,4 bonds in polysaccharides.
Malrotation
Midgut herniates at 4th week and returns approx. 10th week. Rotates around the axis of SMA 270 degrees in counterclockwise direction Final Position (ligament of Treitz LUQ/cecum RLQ)
Complete nonrotation is the most frequent
Forming no C-Loop, the ligament of treitz on the right side of the abdomen and does not cross midline.
Presentation First month of life Bilious emesis Lethargic Toxic (if late)
Diagnosis
Plain abdominal x-ray
Upper GI contrast study
Duodenum the right side of abdomen with birds beak
Management IV fluid resuscitation Placement of nasogastric tube Foley catheter placement Ladd’s procedure
Ladd’s procedure Evisceration and detorsion Division of ladd’s bands (ascending colon to duodenum) Broadening of the mesentery appendectomy
Pyloric Stenosis
1st born males
Improper innervation of pyloric smooth muscle
Projectile, non-bilious vomiting
May have recent history of “formula intolerances”
Baby acts hungry
Eventually will become dehydrated
No tears when baby cries
Infrequent wet diapers
Lethargy
Nature of emesis:
What color is it?– the most important question to ask
Non-bilious, curdled milk/formula, could have rust tint if presentation has been delayed
Bilious… not pyloric stenosis, could be midgut volvulus
Can be catastrophic (fatal) if not recognized
Intussusception
Clinical Triad of Symptoms:
Colicky abdominal pain
Bilious emesis
“Currant jelly” stools
Management– Barium Enema
Meckel’s Diverticulum
Small bowel diverticulum— TRUE diverticulum
2% of population Within 2 feet of ileocecal valve 2 types of heterotopic tissue: gastric (50%) and pancreatic 2 inches in length 2 year old
Hirschsprung’s Disease
Absence of Ganglion cells in the myenteric and submucosal plexus
Aganglionosis always involves distal rectum
Abdominal distention
Bilious emesis
Failure to pass meconium in the first 24 HRs
Omphalocele
abdominal contents sticking out WITH a sac
Gastroschisis
abdominal contents sticking out WITHOUT a sac
Acinar cells
secrete digestive enzymes
Gastric phase: activated by parasympathetic efferents (ACh) from vagal centers in the brain and secondary to gastrin release
Intestinal phase: activated by vago-vagal reflex and
by fat/amino acids in duodenum- I cells release CCK
Ca most important for signaling
Centroacinar cells
dilute pancreatic enzymes and make rich in sodium and bicarbonate
duct cells
dilute pancreatic enzymes and make rich in sodium and bicarbonate
H+ ions cause S cells to release secretin activating ductal cell secretion of bicarbonate
Regulation of CCK
During cephalic and gastric phases, vagal stimulation causes release of pancreatic enzymes including Monitor Peptide.
During intestinal phase, amino and fatty acids cause release of CCK-RP.
CCK-RP and Monitor Peptide causes release of CCK from I cells into the blood.
CCK increases release of Monitor peptide and pancreatic enzymes.
Pancreatic enzymes digest luminal nutrients, CCK-RP, and Monitor peptide turning off CCK secretion
Activation of Pancreatic Enzymes
Enteropeptidase from duodenal brush border membranes cleaves trypsinogen to its active forms trypsin.
Trypsin then activates lipases and endopeptidases chymotrypsin and elastase.
Pancreatitis
Causes:
Cystic fibrosis
Occlusion of pancreatic duct: gallstones, malignancy
Alcohol can be metabolized into products that cause hyperstimulation of acinar cells resulting in intracellular trypsin activation and cell death.
Effects:
Upper abdominal pain from autodigestion of pancreatic tissue can lead to vomiting and sympathetic activation
Enzymes spill over into circulation- elevated serum amylase and lipase levels.
Malabsorption of fat and fat-soluble vitamins (A,D,E,K) steatorrhea
Malignancy, Diabetes, and Infections
GLP-1
an incretin -> increased insulin and decreased glucagon
Oral glucose leads to higher insulin than IV glucose since glucose causes a release of glucagon-like peptide-1 (GLP-1) from intestinal L cells and glucose-dependent insulinotropic peptide (GIP) from K cells
satiety signalling cytokines
GLP1, CCK, Insulin, and Leptin
Ghrelin
a peptide hormone produced in fundus of stomach during fasting stimulates appetite (orexigenic) and decreases energy expenditure through neuropeptide Y and agouti-related peptide
Kupffer cells
type of macrophage
Stellate cells
produce collagen
and store lipids like vitamin A
gallbladder contraction
During intestinal phase, CCK and vagal efferents activate gallbladder contraction and relaxation of the sphincter of Oddi
Cholestasis
- impaired bile secretion
Primary Biliary Cirrhosis (destruction of cholangiocytes)
Primary Sclerosing Cholangitis (inflammation of bile ducts)
Pregnancy- progesterone reduces gallbladder smooth muscle tone
Effects:
Bile accumulates in liver leading to metabolic dysfunction
Itching associated with bile regurgitate into the plasma
bile salts can be excreted into the urine
Hypercholesterolemia- cholesterol aggregation “lipoprotein X”
Deficiency of fat soluble vitamins
Cholelithiasis
Range from grain of sand to golf ball size (20% of population);
Symptoms: upper right quadrant abdomen pain, fever, many people lack symptoms
- Cholesterol stones- due to increased cholesterol or decreased bile acids treat with bile acid- ursodeoxycholic acid,
Less common pigment stones (calcium salts of unconjugated bilirubin)
Hemolytic anemia, infection of biliary tract leads to deconjugation
Outcome of blockage depends on where blockage is occurring jaundice, steatorrhea, and bleeding disorders
Hartnup disease
Inherited mutations in the SLC6A9 transporter (Bo) result in Hartnup disease. This condition results in the symptoms of pellagra because tryptophan is not absorbed or resorbed and can not be used to synthesize niacin.
AMPK
Activation of AMPK inhibits protein synthesis and promotes autophagy.
mTORC1
The mTORC1 complex activates protein synthesis and inhibits autophagy.
ApoB-48 o
ApoB-48 is the major apoprotein of chylomicrons. It is encoded by the same gene as ApoB-100, the apoprotein of VLDL.
RNA editing produces ApoB-48 in intestinal epithelial cells. The unedited transcript produces full length ApoB-100 in hepatocytes
After chylomicrons enter the blood, they receive ApoCII and ApoE from high density lipoprotein (HDL).
Fatty acids and cholesterol taken up by the liver from chylomicron remnants can be repackaged with ApoB100 as very low density lipoprotein (VLDL).
VLDL serves a similar function as chylomicrons: To deliver fatty acid fuels to the tissues of the body.
Lipoprotein lipase (LPL)
Lipoprotein lipase (LPL) is an extracellular lipase in the capillary beds of muscle and adipose tissue. It is activated by ApoCII
ApoB100
RNA editing produces ApoB-48 in intestinal epithelial cells. The unedited transcript produces full length ApoB-100 in hepatocytes
After chylomicrons enter the blood, they receive ApoCII and ApoE from high density lipoprotein (HDL).
Fatty acids and cholesterol taken up by the liver from chylomicron remnants can be repackaged with ApoB100 as very low density lipoprotein (VLDL).
VLDL serves a similar function as chylomicrons: To deliver fatty acid fuels to the tissues of the body.
Aphthous ulcers
(canker sores): very common, shallow, superficial mucosal ulcerations, usually painful and often recurrent. Etiology is uncertain, with a variety of causes suggested (including minor trauma, local food sensitivity, and stress), but some may be associated with celiac disease or inflammatory bowel disease. Typically spontaneously regress within several weeks.
Fibroma (irritation fibroma)
reactive proliferation of squamous mucosa and underlying subepithelial fibrous tissue, typically secondary to chronic irritation.
Pyogenic granuloma
polypoid red lesion, composed of lobular reactive proliferation of capillaries (eruptive hemangioma). Usually occurs on the gingiva in children, young adults, pregnant women.
Glossitis
defined as inflammation of the tongue, but also used to describe the beefy-red appearance of the tongue encountered in certain deficiency states, such as vitamin B12 deficiency. Red appearance is secondary to atrophy of the papillae of the tongue and thinning of the mucosa. Combination of iron-deficiency anemia, glossitis, and esophageal dysphagia associated with esophageal webs is known as the Plummer-Vinson syndrome.
Geographic tongue
(benign migratory glossitis): migratory “map like” appearance of the tongue, due to focal loss of the papillae with formation of smooth red patches. Microscopically, intraepithelial neutrophilic inflammation is present. Patients are usually asymptomatic, but some may experience a mild burning sensation. Etiology is unknown; however, this condition does tend to run in families so there may be a genetic component.
Bisphosphonate-related osteonecrosis of the jaw
Bisphosphonate medications (such as Fosamax) are used to treat osteoporosis. One side effect with the use of this class of medication is focal mandibular and maxillary osteonecrosis. In some cases, the osteonecrosis occurs following minor trauma (such as a dental procedure).
Odontogenic cysts and tumors
odontogenic derived epithelial lined cysts of the jaws are common. Most common cysts include dentigerous cyst (originates around the crown of an unerupted tooth), odontogenic keratocyst (typically locally aggressive with high rate of recurrence), and periapical cyst (inflammatory). Many types of odontogenic tumors exist, with the most common and significant tumors being ameloblastoma and odontoma
Hairy leukoplakia
White, confluent patches of “fluffy” hyperkeratosis on the lateral sides of the tongue. Unlike thrush (candida infection), the lesion cannot be scraped off.
Occurs in immunocompromised individuals (HIV infection, treated cancer patients, organ transplant patients) secondary to EBV infection.
May be the first presenting sign of HIV infection.
Squamous papilloma
Exophytic papillary proliferation of squamous mucosa with fibrovascular core.
Some are associated with HPV infection; others may represent reaction to trauma/irritation.
Some squamous papillomas can undergo malignant transformation to in-situ and invasive squamous cell carcinoma.
Actinic cheilitis
Leukoplakic lesion of the lower lip with loss of the distinct demarcation between the lower lip vermilion border and the skin of the lip (above right, arrows); histologic findings include disordered maturation of the epithelium with cytologic atypia, increased mitotic activity, hyperkeratosis, and connective tissue solar changes
Nasopharyngeal angiofibroma
benign neoplasm composed of admixture of vascular and fibrous tissue. Occurring almost exclusively in young adolescent males and men before the age of 25. Most common clinical complaints are persistent nasal obstruction and epistaxis.
Sinonasal (Schneiderian) papillomas
typically occuring in adults, these are benign neoplasms arising from the sinonasal (Schneiderian) mucosa and are composed of a squamous or columnar epithelial proliferation. These papillomas occur in three forms: exophytic (septal), inverted, and oncocytic (columnar). The first two types can sometimes be associated with HPV. All of these papillomas can recur if incompletely excised, but the inverted type, which arises from the lateral nasal wall, is especially prone to recurrence to due its inverted growth pattern. Malignant transformation can also occur in the inverted and oncocytic papillomas
Nasopharyngeal carcinoma
rare tumor in the USA, but common in Africa (one of the most frequent childhood cancers in that location) and common in southern China (typically adults, rare in children at that location). There are three patterns of nasopharyngeal carcinoma: keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, and undifferentiated carcinoma. The last two patterns exhibit a strong association with EBV, and components of the EBV genome can be detected in the tumor cells. These tumors are frequently occult, and the first presentation can be metastasis in the cervical lymph nodes.
Laryngeal squamous papillomas
benign papillary squamous neoplasms, often times caused by HPV.
Xerostomia
defined as dry mouth due to decrease in the production of saliva. Causes include Sjogren’s syndrome, previous radiation therapy, and side effect of prescribed medications.
Sialadenitis
defined as inflammation of the salivary glands. Many causes, including trauma, bacterial or viral infections (e.g. mumps), and autoimmune disease (e.g. Sjogren’s syndrome). Sialolithiasis (stone in the salivary duct) can lead to obstruction and secondary bacterial infection (often Staphylococcus aureus or Streptococcus viridans).
Mucocele
results from either blockage (retention mucocele) or traumatic injury (extravasation mucocele) to a minor salivary gland, with leakage of contents into the surrounding connective tissue stroma. Presents as a fluid filled mucosal nodule with varying degrees of inflammation. A ranula is a mucocele that arises when the sublingual duct is damaged. Ranulas can become quite large and dissect into the neck (plunging ranula).
Lymphoepithelial sialadenitis
Autoimmune disease involving the salivary glands.
Many of the cases (50%) represent salivary gland manifestations of Sjogren’s syndrome, a systemic autoimmune disease which can have involvement of the major and minor salivary glands and the lacrimal glands (dry mouth and dry eyes (keratoconjunctivitis sicca).
Pathologic features are polyclonal lymphoid inflammation of the salivary gland, leading to gland enlargement and characteristic lymphoepithelial lesion.
Other entities can cause morphology similar to LESA, such as HIV-associated sialadenitis (benign lymphoepithelial cysts).
Pathologic findings of LESA need to be distinguished from primary lymphoma of the salivary gland, many of which have the morphology of B-cell MALT lymphoma (although other types of lymphoma can occur).
Pleomorphic Adenoma
Most common salivary gland tumor; usually found in the parotid gland.
Benign tumor consisting of a mix of proliferating epithelial (ductal and myoepithelial) cells, associated with a mesenchymal matrix of myxoid, hayline, and chondroid (cartilaginous-like) tissue. It may be that all neoplastic tissue elements in this tumor may be of ductal or myoepithelial origin, hence the term pleomorphic adenoma.
Tumors typically present as painless, discrete masses. While seemingly well circumscribed, they have small extensions or protrusions such that simple enucleation of the tumor will lead to a recurrence rate of 25%.
Rarely, a carcinoma will arise in a pleomorphic adenoma. This typically occurs in tumors of long duration, and the carcinoma is often times poorly differentiated and high grade. Such tumors are called “carcinoma ex pleomorphic adenoma” or “malignant mixed tumor.”
Warthin Tumor
Second most common salivary gland tumor, found almost always in the parotid gland.
Multifocal in 10% and 10% are bilateral. Smokers have 8 times the risk of developing this tumor than nonsmokers.
This benign tumor is well encapsulated with a distinct microscopic appearance, demonstrating a papillary, cystic lesion with a dual layer of bland, neoplastic, eosinophilic (oncocytic) epithelium, associated with reactive lymphoid stroma.
Mucoepidermoid carcinoma
Most common malignant salivary gland tumor and the most common malignant salivary gland tumor in children.
Approximately 60-70% occur in the parotid gland.
Composed of a variable mixture of squamous cells, mucus-secreting cells, and intermediate cells.
While tumors grossly appear encapsulated, they often infiltrate at the margins microscopically.
Clinical course is dependant on the grade of the tumor: low grade tumors recur in about 15% of cases, and have a 5-year survival rate of more than 90% due to low frequency of metastases; high grade tumors recur in 25-30% of cases with a 5-year survival rate of only 50%.
Vitamin A
In the body, the alcohol of trans-retinol can be converted to:
aldehyde
carboxylic acid
ester with fatty acid (e.g. palmitate)
Found in: Red, yellow, orange fruits and vegetables.
Retinoic acid is soluble enough to be transported in the blood associated with albumin. Retinyl-fatty acid esters are transported in chylomicrons.
Stellate cells in the liver serve as the reservoir for Vitamin A storage.
Hepatocytes mediate retinol homeostasis in the body.
Retinyl esters go in. Sources:
Dietary: Chylomicrons
Stored: Stellate cells
Retinyl esters go out to. . .
Stellate cells (storage)
VLDL (to tissues)
Retinol goes out to serum in complex with transthyretin and retinol binding protein (RBP).
Retinoic acid goes out to serum complexed to albumin.
Retinol is important for vision, and vitamin A deficiency can manifest as night blindness. Vitamin A toxicity can result in blurred vision.
cis-retinal bound to the protein opsin is the photoreceptor rhodopsin. Light causes conversion to trans-retinal. Rhodopsin bound to trans-retinal activates a heterotrimeric G protein, closure of a Na+ channel, hyperpolarization of the rod cell, and signaling to the neuron.
Retinoic acid acts as a ligand for the retinoic acid receptors (RAR), retinoic X receptors (RXR) and some peroxisome proliferator activated receptor (PPARb and PPARd).
RAR, RXR, and PPAR act as ligand activated transcription factors.
Vitamin A deficiency: anorexia retarded growth increased susceptibility to infections alopecia keratinization of epithelial cells eyes: night blindness xeropthalmia (dry eye due to keratinization) Bitot’s spots
Doses in vast excess of this can cause. . . nausea vomiting blurred vision headache desquamation of skin alopecia ataxia liver damage (from excess stellate cell growth and proliferation) conjunctivitis, eye pain
Adenoid cystic carcinoma
Slow growing, often relentless salivary gland carcinoma with predilection for neural invasion.
While this tumor can occur in the major salivary glands, approximately 50% occur in the minor salivary glands (most common malignant tumor of the minor salivary glands).
Despite surgical resection, 50% disseminate to lungs, bone, liver, and brain, often decades after removal. While 5-year survival rate is 60-70%, survival drops to 30% at 10 years and 15% at 15 years.
Acinic cell carcinoma
Malignant salivary gland tumor composed of neoplastic epithelial cells resembling salivary gland acinic cells.
Survival at 5 years is approximately 90%, but drops to 60% at 20 years.
Salivary gland adenocarcinomas
Salivary duct carcinoma: microscopically resembles ductal breast carcinoma, typically seen in the elderly in the major salivary glands.
Polymorphous low-grade adenocarcinoma: usually seen in the minor salivary glands, often in the palate.
Esophageal mucosal webs
protusions of mucosa that can cause obstruction; usually seen in the upper esophagus; upper esophageal webs associated with chronic iron-deficiency anemia, glossitis, oral leukoplakia, and spoon nails is known as the Plummer-Vinson syndrome.
Esophageal rings (Schatzki rings)
like webs but thicker and circumferential; may contain muscularis propria; located in the lower esophagus.
Zenker’s diverticulum
Located above the upper esophageal sphincter as an outpouching of mucosa and submucosa through a weakend posterior cricopharyngeus muscle; not a true diverticulum.
This diverticulum can become large enough to accumulate food, producing a mass and symptoms of painful swallowing, halitosis, regurgitation, and diverticulitis.
