Monday, 4 July 2016

LES - drugs, alcohol, CAFFEINE, and chocolate

Pathophysiologic Bases of Health Deviation 437

Gastrointestinal System

Pharynx:  Oropharynx (palatine tonsils)
·         Important for immunity
·         Considered “lymph nodes”
·         First line of defense
·         Viruses can cause pus on tonsils as well as bacteria (strep can cause abdominal pain and enlarged nodes, but so can viruses).
·         Peritonsillar abscess:  105 degree fever, tonsil covered with pus.  May need to hospitalize for IV antibiotic therapy
·         If tonsils are not symmetrical, think lymphoma.
·         Should not have to treat “strep” for months
Pharynx:  Nasopharynx (adenoids or pharyngeal tonsils)
·         Adenoids are located in front of the Eustachian tubes
·         Adenoiditis à snoring à poor sleeping à decreased production of growth hormone
·         Can remove adenoids without taking out tonsils
Pharynx:  Laryngopharynx (epiglottis)
·         Incidence of epiglottitis is decreasing….? Due to H. flu vaccine?
·         S/S of epiglottitis:   tripod position, drooling, elevated temperature.  DON’T lie the person down, and DON’T use a tongue blade.  This is an emergency…have an airway ready
Relationship of the pharyngeal musculature with CN IX (glossopharyngeal) and CN X (vagus)
·         Uvula should hang straight down
·         CN IX and X help you to handle secretions.  They work together in the head and neck.
·         Palate closes off the nasopharynx…have the patient say K-K-K.  If able to do this OK, then IX and X are working OK (patients with cleft palate can’t do it)
·         Guillain-Barre:  if onset is bulbar (brainstem), NOT peripheral, it will be in CN IX (can occur after gastroenteritis with Campylobacter jejuni or after EBV)
·         CN X = Vagus; goes through the mediastinum.  A branch of the nerve, the recurrent laryngeal nerve, flips back up to supply the vocal cords.  Hoarseness occurs with irritation or compression of this nerve.
·         Causes of hoarseness:
·         Lung cancer
·         Thyroid enlargement, thyroid Ca, inadvertent nerve damage during thyroid surgery
·         Laryngitis
·         Ca of larynx
·         Aneurysm of arch of aorta (will also have pulsating bulge at 2nd ICS)
·         Angioedema (angioneurotic edema)
·         = side effect of ACE-inhibitor (-pril)
·         = localized anaphylaxis in the back of the throat
·         Happens in 2% of patients placed on –prils
·         It is an allergic reaction, so IgE-mediated
·         If severe, treat with epinephrine
·         If this reaction occurs, the patient should consider all “-prils” as allergy

The tongue

·         Reservoir for water, so can check it for dehydration and hypothyroidism (can’t get rid of CO2 and water…vocal cords will also swell, so voice deepens and tongue swells (look for indentations on edge of tongue where teeth are)
·         In Down’s syndrome, the tongue is not too big…the mouth is too small
·         Thrush (Candida) due to drugs such as steroid inhalers and antibiotics, diabetes mellitus, and immunosuppression
·         Sublingual vessels:  blood supply from portal system (could see varices with increased pressure here before bleed occurs)
·         Must have saliva under tongue in order to absorb nitroglycerin.  Saliva is produced due to CN VII stimulation by ACh.  Elderly on anticholinergics have decreased amount of saliva, so need to use nitro spray


·         Petechiae on palate may be due to
·         Intense vomiting due to bulimia, anorexia nervosa, alcoholic
·         Strep throat (20% of time)
·         Subacute bacterial endocarditis (SABE)
·         May also have petechiae on conjunctiva and fundus; splinter hemorrhages under nails, low grade temp, SOB, malaise, fatigue

Associated glands

·         Parotid glands = Stenson’s ducts
·         Sublingual glands = Worten’s ducts
·         Functions of the glands:  production of saliva (1.5 L/day), regulation of water balance (saliva)
·         Parotid gland secretes amylase (extracellular enzyme also produced by the pancreas)


·         LES = lower esophageal sphincter = cardiac sphincter
·         The LES is a physiologic, not an anatomic, sphincter
·         Tightened by ACh (vagus nerve)…does most work at noc when reclining, especially between 4-6 am
·         Loosened by dopamine
·         GERD (gastroesophageal reflux disease) = reflex esophagitis
·         Causes
·         Anticholinergics
·         Bronchodilators loosen the sphincter
·         Nocturnal cough is often result of GERD
·         Bronchodilator opens LES à allows acid to move up into esophagus à vagus nerve responds by clamping esophagus, but also causes bronchoconstriction à patient uses bronchodilators again to help breathing à LES opens more à vicious cycle!
·         Acid backup, so need to reduce acid
·         Need to decrease acid before bedtime with histamine-2 blocker.  If no response, use proton pump inhibitor (omeprazole [Prilosec], Prevacid, AcipHex, Nexium)
·         Other causes of LES relaxation:
·         Drugs:  nitroglycerin, calcium channel blockers, beta-agonists, anticholinergics
·         Alcohol
·         Caffeine
·         Smoking (take nicotine patches off at noc)
·         Chocolate
·         Peppermint
·         Fatty foods
If asthma symptoms at noc, check for GERD (may start to cough as they lie back on the exam table)
If nocturnal cough and no GERD, have severe asthma.


·         Fundus = location of gastric bubble
·         Antrum = where acid is produced
1.       Gastric cells produce:
  1. gastrin
  2. gastric alcohol dehydrogenase (one line of alcohol metabolism)
Females have 30-50% less of this than males, so in females, alcohol goes straight to blood (bolus to brain and liver), so females get cirrhosis a decade earlier than males
2.       chief cells produce pepsinogen, a protease enzyme which breaks down protein
3.       mucus cells produce mucus
  1. mucus is produced because of prostaglandins
  2. prostaglandins also produce bicarbonate to balance acid
  3. NSAIDs à decreased mucus à gastric ulcers
Causes of gastric ulcers:  NSAID use and H. pylori (stress may contribute, but NSAID use or H. pylori would need to be present)
4.       parietal cells produce HCl and intrinsic factor, the glycoprotein needed for vitamin B12 absorption (B12 needed for RBC/WBC production and nervous system function)
  1. Intrinsic factor is destroyed by 1) autoimmune disease (pernicious anemia) and 2) gastrectomy
  2. With pernicious anemia, needs IM B12.  If no supplemental B12 à peripheral neuropathy and severe dementia, like Alzheimer’s. 
  3. Treatment: 1000 mcg daily X 4 weeks, then 1X/week X 1 month, then monthly.  Improve in 2-4 weeks
Small Intestine:  receives chyme from the stomach, pancreatic juices from the pancreas, and bile from the gall bladder.  Major function is the digestion of foodstuffs.
·         Duodenum
·         Produces CCK (cholecystokinin), the hormone of satiety (“fullness”)
·         Animals pay attention to “full”, but humans often don’t
·         Organ of nausea due to serotonin release; can be blocked by Zofran
·         Jejunum and ileum
·         Puts out 5,500 cc of fluid/day
·         Celiac sprue = gluten allergy to wheat; increased risk of cancer of small intestine
·         Crohn’s disease = one type of inflammatory bowel disease
·         Can occur anywhere from esophagus to anus, but 60% occurs in ileum
·         A disease of the entire thickness of the bowel wall (ulcerative colitis is of the superficial layer only)
·         Cause:  ? mycobacterium (organism close to TB)
·         Treatment:  currently prednisone, Imuran; surgery not successful
·         Current research:  treat with INH and rifampin
·         S/Sx mimic appendicitis:  diarrhea, weight loss, RLQ pain, B12 deficiency (= anemia of malabsorption)
·         Increased risk of cancer of bowel, but even higher risk with ulcerative colitis
·         Appendix
·         Has immune function, but not essential to immune system
·         S/Sx:  RLQ pain, rebound tenderness, (+) psoas sign
·         If appendicitis is walled off, the WBC will be OK

Large Intestine

  • Normal flora takes 3 months to appear
  • Clostridium difficile from antibiotic therapy
  • Net absorption of water in large intestine is 1,300 cc (higher in small bowel)
  • Secretion of K+ from large bowel (in hyperkalemia, can give Kayexolate enemas)
  • Glandular cells produce mucus
  • Glandular cells (“Adeno”-) can become cancerous (= adenocarcinoma)
  • Movement/storage of feces via ACh (needed to move drugs through system as well)
  • Decreased peristalsis from:
    • Anticholinergics
    • Calcium channel blockers (Verapamil causes constipation in 30% of patients; don’t give to the elderly (occurs because calcium helps muscle to contract; if blocked by medication, peristalsis also blocked)
    • Elavil (very anticholinergic)
  • Nicotine increases peristalsis (so if stop smoking, may become constipated)
  • Opiates decrease peristalsis (--> constipation, obstipation).  Codeine is very constipating.
    • Lomotil, an opiate-derivative, stimulates Mu receptors in the brain, leading to euphoria.  Immodium is the same thing without the CNS effects.
  • Ulcerative colitis
    • Etiology is multifactorial (infectious, genetic, immunologic, psychologic)
    • Clinical manifestations:  bloody diarrhea, low back pain, tenesmus (spasmodic contraction of anal sphincter with pain and persistent desire to empty the bowel, with involuntary ineffectual straining efforts), iron-deficiency anemia
    • Treatment:  sulfasalizine (antibiotic), Rauwosa enemas
    • High risk of cancer (the longer the length of time with the disease, the higher the risk of cancer)
    • Monitor with sigmoidoscopy every 6 months:  look for dysplasia, may be low grade or high grade.  If high grade, needs surgery. (regeneration --> hyperplasia --> metaplasia --> dysplasia --> cancer)
    • Can get both Crohn’s and ulcerative colitis
  • Adenocarcinoma of the bowel
    • Etiology: 3X higher risk due to genetics
    • Larger polyps:  increased risk of cancer in situ (not through base membrane)
    • Fat is a carcinogen to the bowel wall.  If stool sits in the distal colon due to lack of fiber, it can take 10 days to pass through, increasing the risk of cancer.  Also, the pressure can cause diverticulosis.
      • GI transit time:  With high fiber, lo-fat diet:  18-72 hours.  With lo fiber, high-fat diet:  72 hours to 7-10 days
      • Need 20-24 gm fiber/day
  • Gastrocolic reflex
  • Irritable bowel syndrome – hyperactive nerves to the GI tract


  • S3-S5 rectal nerve supply
  • Anal wink used to check bowel and bladder function in neurology for spinal cord injury and nerve problems
  • Site for herpes
  • Portal of entry for HIV (mucosa easily torn)
  • Human papilloma virus (HPV) causes genital warts; also an oncogenic virus.  Has led to > 450% increase in the last 10 years of squamous cell carcinoma of the rectum, vagina, vulva, and cervix

The Liver
  • Has capacity to regenerate (can remove up to 80% of the organ and it can still regrow)
  • Most of the liver is located to the right side of midline
  • If enlarged, the liver pushes on the diaphragm, causing referred pain to the shoulder (all referred pain is embryonic in origin)
  • Major functions of the liver include:
    • Conjugation of bilirubin and excretion into bile ducts
    • Production of albumin
    • Synthesis of clotting factors
    • Inactivation of hormones, toxic substances, drugs
    • Extramedullary hematopoiesis (normal RBC production in the fetus)
    • Metabolic functions (production of lipoproteins)
    • Storage functions via macrophages, also stores blood
  • Bilirubin
    • Waste product of RBC destruction by spleen.  Made water soluble by the liver
    • Conjugated (direct) bilirubin (water-soluble) in liver --> bile ducts --> GI tract (stool) – plus small amount reabsorbed --> enterhepatic circulation --> kidneys (urine)
    • Unconjugated (indirect) bilirubin (lipid-soluble):  from spleen --> lymph system --> blood vessels
    • Direct bilirubin goes up in biliary disease
    • Bilirubin has to go up to 2 for clinical jaundice to occur (5 in a neonate) – jaundice will first appear under the tongue and on the palate
  • Production of albumin
    • Normal range 3.5-5.0 gm/dL
    • Albumin holds water in the vascular system (osmotic pressure)
    • If hypoalbuminemic --> can’t keep fluid in vascular system --> third spacing (ascites)
    • Albumin is the major protein which binds drugs, such as digoxin, Coumadin (Caution:  albumin is decreased in the elderly)
    • Albumin tells you how much of drug is bound and how much is free
  • Synthesis of clotting factors
    • Synthesizes II, VII, IX, and X
    • Factor VII is inhibited by Coumadin (takes 4 days to occur following initiating Coumadin therapy)
  • Inactivation of substances
    • Metabolizes substances to an inactive form (except Demerol, which is metabolized to normeperidine.  This metabolite causes hallucinations in the elderly.  Don’t give more than 48 hours in patients --> CNS toxicity --> hallucinations, possible seizures
    • If liver is not working, body cannot inactivate hormones:
      • Increased estrogen in male --> gynecomastia, shrinkage of penis/testicles
      • Increased estrogen in female --> palmar erythema, spider angioma (dilated end arterioles)
      • Increased aldosterone --> retain Na+ and water --> volume overload (treat with aldosterone blockers, such as spironolactone)
      • Increased ADH --> retain fluid
    • If unable to rid body of ammonia --> encephalopathy (S/Sx “liver flap”)
  • Extramedullary hematopoiesis
    • In the fetus, the liver produces RBCs
    • Liver and spleen retain ability to produce RBCs after birth
    • In severe long-standing sickle cell anemia, the liver and spleen kick in and start producing RBCs (teardrop RBCs which will show in a peripheral smear)
  • Production of lipoproteins
    • HDL = “good cholesterol” – carries cholesterol to the GI tract to be excreted
    • LDL = “bad cholesterol” – carries cholesterol to the arteries
    • VLDL – carries triglycerides
    • Total cholesterol: HDL ratio
      • If > 4, person is at high risk for heart disease
      • The total cholesterol: HDL ratio is more indicative in females
      • In males, need to look at LDL and risk factors
    • HMG CoA reductase is an enzyme important for LDL production by the liver.  It works at night.  Stress in the AM --> release of cholesterol from the night --> cholesterol levels in the AM
      • HMG CoA reductase is inhibited by the –statin drugs:  lovastatin (Mevacor), simvastatin (Zocor) pravastatin (Pravachol), fluvastatin (Lescol).  Lipitor decreases both LDL and VLDL
    • Ways to increase HDL levels
      • Exercise
      • Estrogen
      • Vitamin E
      • Eat right (beans, fiber, tuna, salmon, halibut)
      • Ethanol (but only if in limited amount: 1 beer/day, 4-8 oz wine/day, or 1 oz liquor/day)  Exceptions to this:  alcoholics, liver disease, and diabetics (alcohol increases triglyceride levels)
        • Tannins in red wine:  vasodilator, decreases platelet aggregation, plasminogen activator)
    • Screen early for diabetes mellitus (C-peptide, proinsulin) and for thyroid
  • Storage function
    • Kupffer cells store iron, B12
    • If liver is lacerated --> DIC due to release of all the clotting factors
  • 70% of the blood supply to the liver is venous; almost impossible to infarct a liver because it doesn’t use much oxygen

Liver Enzymes

  • Hepatocellular enzymes: do work in the hepatocytes (elevation indicates problem in liver parenchyma)
    • AST (formerly SGOT) - found in liver, heart, skeletal muscle, brain, spleen, pancreas, lung, and renal tissue
    • ALT (formerly SGPT) - 99% found in liver
  • Hepatobiliary enzyme:  indicates a Biliary problem, usually requiring gallbladder surgery
    • Alkaline phosphatase - found in cells lining biliary tree, also bone
  • If jaundiced:
    • Alk. phos. increases 8X and AST/ALT 2X = surgical:  obstructive problem
    • AST/ALT increase 10X = medical:  probably liver problem (hepatitis due to virus like CMV, EBV, or toxoplasmosis, drug-induced, alcohol, or obesity (fatty liver --> -itis)
  • Normals for both AST and ALT are about 50.
  • AST is especially sensitive to alcohol.  In patients with alcoholic liver disease, the AST level is at least twice the level of ALT.
  • AST/ALT ratio > 1 in alcohol-induced hepatitis (AST > ALT)
  • AST/ALT ratio < 1 in viral or drug-induced hepatitis (AST < ALT)
  • Acetaminophen is liver toxic, especially with patients on DepaKote or Depakene (synergistic in killing liver).
  • Many herbal medicines are hepatotoxic, so ask patients about “health foods” they may be taking.
  • Increased alk. phos. and jaundice are found in biliary cirrhosis, an autoimmune problem found primarily in women.  To assess for this problem, check antimitochondrial antibodies.  Patients with this problem cannot get a new liver.
  • Alk. phos. is also found in bone being actively laid down:
    • 6X normal level - during 1st year of life and in teenagers
    • 20X normal level - osteoblastic sarcoma, breast/prostate cancer metastasized to bone (causes osteoblastic stimulation)
    • Multiple myeloma - stimulates osteoclasts; will have normal or low alk. phos.
“Portal” means “large vein that connects 2 capillary beds”.  There are 2 portal systems:
1.       GI --> liver
2.       hypothalamus --> pituitary

Portal hypertension

  • Due to hardening of the liver (liver cirrhosis, liver fibrosis, liver sclerosis)
  • Types of cirrhosis
    • Alcohol (Laeneec’s) cirrhosis:  females affected 10 years earlier than males
    • Biliary cirrhosis:  seen in babies as Biliary atresia, in women as an autoimmune disease, and in cystic fibrosis
    • Post-necrotic cirrhosis:  secondary to drugs, toxins, viruses (e.g. Hepatitis B & C)
  • Liver hardens --> blood backs up --> liver swells --> varices, ascites (third spacing occurs, meaning the fluid is pushed out; physiologically inactive)
  • Treatment of varices:
    • Sclerotherapy
    • Compression therapy (tamponade)
    • Pitressin
    • Beta-blockers to decrease cardiac output (works in 15% of cases of varices)
    • Magnesium/lactulose given to decrease ammonia due to breakdown of blood in colon after varice bleeds (ammonia --> encephalopathy)
    • Surgical: portal systemic shunt


  • Early S/S:  headache, malaise, anorexia, flatus, change in bowel habits, N, V, dull ache RUQ, smokers lose interest in smoking
  • End stage liver failure looks the same regardless of the type of cirrhosis
  • Late S/S due to liver cell failure and portal hypertension:
    • Jaundice
    • Elevated estrogen causes spider angiomas, gynecomastia, palmar erythema, loss of secondary sex characteristics
    • Bleeding tendencies
    • Anemia
    • Ascites
    • Peripheral edema
    • Hepatic fetor (liver breath, or mousy odor to breath)
    • Coma
    • Portal hypertension with esophageal varices
    • Caput medusae (varicose veins on the stomach)
    • Hemorrhoids
    • Splenomegaly


  • Should not be palpable in adults unless 3X normal size
  • Is palpable in neonates and up to 1 year of age
  • Can regenerate up to age 12 (within 6 weeks)
  • Important for humoral immunity; try not to remove if possible
  • Kehr’s sign:  left shoulder pain with spleen rupture or enlargement or bleeding under capsule


  • Has two parts:  head and tail
  • The head of the pancreas is the exocrine portion, which releases enzymes into the 2nd portion of the duodenum
    • Pancreatic enzymes (amylase, lipase) are extracellular.
      • Amylase is found in the pancreas and the parotid gland.
      • Amylase is elevated in:
        • acute pancreatitis (12,000-60,000) due to alcohol, gallstones (if gallstones, alk. phos. will also be increased), or hypertriglyceridemia
        • mumps (elevated with mumps orchitis)
  • The tail of the pancreas is toward the back, and handles the endocrine function (Islets of Langerhans)
  • Acute pancreatitis usually doesn’t affect blood sugar.  The “autodigestion” which occurs, starts at the head of the pancreas, where the exocrine function is located
    • S/S:  severe epigastric pain, may refer to back, N, V, low grade fever, acute tubular necrosis
    • Causes:  80% of cases due to alcohol or gallstones, other causes include high triglycerides (as in diabetes mellitus), estrogen-containing birth control pills (estrogen causes cholestasis)
    • Treatment:  low on fluid (third spacing may be as high as 6 liters) so hydrate
      • Don’t use morphine for pain (causes spasm of Sphincter of Oddi)
      • Use:  Dilaudid
    • Two types
      • Hemorrhagic
      • Non-hemorrhagic
    • Check lipase and amylase (lipase is only in the pancreas)
    • May have low calcium:  Lipase chews through fat into the mesentery --> calcium moves in the fat.  This is why they watch for calcifications on breast mammograms…indicate something (cancer) has chewed through the fatty breast tissue.  Calcifications can also be caused by trauma.

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