Synopsis of Anatomy / Physiology / Pathophysiology / Pharmacology

Arranged by body system: Dr. Kelner Gastrointestinal Pathophysiology and Pharmacology I. Basic anatomical and physiologic concepts A. Gross Anatomy and Physiology 1. The GI tract consists of a long tube (the alimentary canal) that extends from the mouth to the anus. 2. There are accessory organs that connect to this tube along the way a. Liver i) Responsible for initial metabolism of nutrients and drugs ii) Receives blood supply from gut via the large portal vein iii) After processing is done, the blood leaves the liver via the hepatic vein and empties into the inferior vena cava iv) The liver also produces Bile necessary for the emulsification of lipids v) The liver is the site of production of many proteins including albumin and clotting factors b. Gallbladder (GB) i) located below and somewhat behind the liver ii) stores bile that is initially produced in the liver iii) bile exits the gallbladder via the cystic ductthis joins with a similar structure leaving the liver called the hepatic ductafter coming together.they form a singular common bile duct (CBD) c. Pancreas i) the pancreas is both an endocrine and exocrine organ. The endocrine function involves the secretion of insulin and glucagon into the vascular system. The exocrine function involves the secretion of digestive enzymes and bicarbonate into the duodenum. ii) the pancreatic duct and the CBD empty into the duodenum via the ampulla of vater iii) pancreatic enzymes consist of peptidases (catabolize proteins), amylase (catabolizes carbohydrates), lipase (lipids) and nuclease (nucleic acids). Note that the amylase produced by the pancreas is not exactly similar to that produced by the salivary glands iv) HCO3- (bicarb) is secreted into the proximal duodenum in response to Secretin. This hormone is released by the duodenum in the presence of low pH v) The duodenum also releases cholecystokinin (CCK) in response

2 to the presence of lipids. The release of CCK stimulates the GB to release bile into the duodenum. 3. The alimentary canal follows this path: epiglottis hiatus/ GES pyloris hepatic flexure Mouth Pharynx Esophagus Stomach duodenum ileocecal valve splenic flexure colon descending colon sigmoid rectum anus Vol. and invol. sphincters B. Digestive physiology and histology 1. Chemical digestion begins in the mouth where the salivary glands release amylase 2. The process of swallowing is called Deglutination 3. The epiglottis closes off the opening of the trachea during deglutination. Problems with this process lead to aspiration. Remember that the Gag reflex is controlled primarily by the ninth cranial nerve (Glossopharyngeal). 4. The bolus of food swallowed is pushed along the esophagus by peristalsis. Remember that there are muscles that are arranged both longitudinally along the esophagus and also circumferentially 5. The esophagus travels through the diaphragm in an opening called the esophageal hiatus. The gastroesophageal sphincter (GES) connects the esophagus to the stomach and prevents retrograde flow during contraction of the stomach. If incompetent, it allows such retrograde flow up into the esophagus which is termed reflux. 6. In the stomach, both chemical and mechanical digestion occurs. a. the parietal cells lining the stomach produce hydrogen ions (protons) which are secreted into the lumen of the stomach. Here they join Cland form HCl. The chemical apparatus in the parietal cell that generates the protons is called the proton pump. b. Acid production and secretion are increased in response to: stimulation of H2 receptors on the stomach the presence of protein in the stomach gastrin release (by the chief cells in the stomach) Jejunum Ileum Cecum ascending colon transverse

3 c. The stomach is protected from its own acid by a protective layer of mucus that coats the stomach wall. The production of this mucus is dependent on the production of certain prostaglandins by an enzyme called cyclo-oxygenase I (COX I). Inhibition of this enzyme by nonspecific NSAIDs is what leads to NSAID related gastritis and PUD. d. Minimal absorption does occur in the stomach. Substances known to be absorbed here include H2O, ASA and ETOH e. The chyme (partially digested food) exits the stomach through the pyloric valve. Rarely, this valve is congenitally stenotic (mostly in males) and leads to dysphagia and projectile vomiting early in life. This is called Pyloric stenosis and needs to be corrected surgically. This usually occurs at about six to eight weeks of age. 7. The duodenum is adherent to the posterior peritoneal wall via ligaments and other connective tissue. 8. The mucosal lining of the GI tract mostly consists of ciliated columnar epithelium. The mucosa forms outcroppings called Villi which serve to increase the absorptive surface area. **For further anatomical and physiologic information, see my notes and/or the text** II. Pathophysiology and pharmacology highlights A. Gastro-intestinal bleeding (GIBs) 1. GIBs are somewhat arbitrarily defined as upper GIBs and lower GIBs. The anatomic structure that defines upper from lower is the ligament of Trietz (one of the structures that holds the duodenum to the back wall). This is located about halfway down the duodenum. 2. Upper GIBs are usually the result of PUD, gastritis, esophageal varicies or malignancy. a. the TYPICAL upper GIB is characterized by the presence of melena (dark tarry stools). This occurs because blood that leaks into the stomach is acted upon by pepsin (a peptidase) found in the stomach. This catabolism results in the formation of pigmented by-products(from catabolism of HgB). Other findings include the possibility of hematemesis, elevated serum BUN (from the previously mentioned digestion). b. if the bleeding is OCCULT (slow enough to occur for some time without being noted), the patient will become anemic and develop fatigue and SOB. c. Rapid acute upper GIBs will lead to hematochezia (bright red or burgundy rectal bleeding) as the blood travels down the GI tract too fast to be catabolized.

4 3. Lower GIBs are usually the result of diverticular disease, internal or external hemorrhoids, polyps or malignancy. a. typical lower GIBs are characterized by hematochezia b. similarly to OCCULT upper GIBs, lower GIBs that are occult will lead to symptomatic anemia 4. Most complete physical exams include a rectal exam. As part of this exam, the examiner should test stool for the presence of blood. This is called a Guaiac test and the brand name is frequently called hemoccult. B. Obstruction 1. Obstructive processes are divided into simple (actual mechanical obstruction) and functional (physiologic cessation of peristalsis). The functional type is called an ileus, or sometimes a paralytic ileus. It is more common then the simple type. An ileus frequently occurs after intra-peritoneal surgery, with chronic illness or severe acute illness. 2. Obstruction is usually heralded by abdominal pain and distention, minimal (if any) bowel sounds, lack of rectal output and occasionally emesis. 3. Simple mechanical obstructions frequently require surgical repair. 4. An ileus is usually treated with initial decompression of the GI tract using an Ng tube hooked up to suction, then slowly advancing a PO diet (starting with clear liquids). 5. If unable to advance diet, the patient may require temporary TPN (total parenteral nutrition) .feeding the patient intravenously. This situation is not beneficial if it lasts for weeks. If a patient requires TPN, most hospitals have a TPN team or nurse that coordinates this therapy. Surgical placement of a large bore central venous catheter is required. 6. Acute absence of bowel sounds in a patient who previously demonstrated them and/or has no obvious reason for an ileus to occur is considered a SURGICAL EMERGENCY. Delay of acute treatment in this situation can lead to perforation or rupture of the GI tract.which usually results in significant morbidity or death. C. Peptic ulcer disease (PUD) 1. PUD is a characterized by a spectrum of abnormalities, ranging from irritation of the stomach or duodenal mucosa with minimal inflammation to erosion / ulceration of the mucosa with perforation. 2. PUD occurs due to: an increase in acid secretion a decrease in production or maintenance of protective mucus a combination of these two factors 3. Risk factors are delineated in the power point notes

5 4. Most cases of persistent or chronic PUD are associated with the presence of a gram negative bacteria called helicobacter pylori (H. Pylori) a. definitive treatment therefore consists of anti ulcer medications plus a regimen of antibiotics b. diagnosis of H pylori involves biopsy and culture (best way) or a breath test that checks for the presence of hydrogen sulfide gas. This is produced by bacterial metabolism of urea by an enzyme called urease 5. Treatment of PUD involves modification of risk factors and pharmacologic therapy. This section is from the GI power point handout (note: there are a few changes which are highlighted):

PUD Treatment

Classes of anti-ulcer drugs

Antibiotics Anti-secretory agents

PUD Treatment

Mucosal protectants Antacids

Histamine 2 Receptor antagonists Proton pump inhibitors

Histamine (H2) Blockers

Inhibit gastric acid secretion by completely blocking H2 receptor on parietal cells Suppress nocturnal and Basal gastric acid secretion by 90-95% and meal stimulated acid secretion by 70-80% Indirectly inhibits pepsin activity All four H2 Blockers are equally effective when taken in equipotent doses

H2 Blockers

Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid)

PUD Treatment

H2 Blockers

PUD Treatment
H2 Blockers (cont.)
Actions Pharmacokinetics Adverse effects Drug interactions Therapeutic uses

Ranitidine (Zantac) Cimetidine (Tagamet) - PROTOTYPE Famotidine (Pepcid) Nizatidine (Axid) All H2 receptor blockers require a dosage reduction in patients with significantly decreased renal or hepatic function

Gastric and duodenal ulcers Gastroesophageal reflux disease Zollinger-Ellison syndrome Aspiration pneumonitis Heartburn, acid indigestion, and sour stomach

Preparations, dosage, and administration

H2 Blockers
Actions
suppress secretion of HCl by parietal cells of stomach can be give orally or intravenously bind to androgen receptors resulting in reversible gynecomastia, reduced libido and impotence

H2 Blockers

Drug Interactions

reduces the activity of hepatic cytochrome P450 -the family of drug metabolizing enzymes

particular concern w/ warfarin, phenytoin, theophylline & lidocaine

antacids decrease absorption w/ po more problems w/ cimetidine

PUD Treatment

Cimetidine (MOST SIDE EFFECTS)

Many drug interactions Anti-androgenic effects with cimetidine

CNS effects with cimetidine

Gynecomastia, reduced libido, impotence

PUD Treatment

Confusion, hallucinations, lethargy, restlessness

There are two mechanisms to decrease the amount of HCl secreted in the stomach decrease the amount of HCl secreted by the parietal cells of the stomach (using H2 blockers) decrease the amount of HCl produced & therefore available

PROTON PUMP INHIBITORS

Drug of choice for hypersecretory conditions Rapid healing of erosive esophagitis and refractory Adverse effects: Headache, nausea, abdominal pain, vomiting, dyspepsia, flatulence Proton pump inhibitors (PPI):

PUD Treatment

Omeprazole (Prilosec) most effective Lansoprazole (Prevacid) Esomeprazole (Nexium)

PUD Treatment

Inhibit activity of the proton pump in the parietal cells Activation of proton pump is final step in acid secretion Abolishes gastric acid secretion in response to any type of stimulus

Omeprazole (Prilosec) most effective

Minimal side effects with short-term therapy; with long-term, concern about possible carcinogenesis

Other PUD Drugs

Mechanism of action Pharmacokinetics Therapeutic use Adverse effects Preparations, dosage, and administration

Mucosal defense agents

Binds selectively to ulcerated mucosa and forms a barrier Protects ulcer from gastric acid and pepsin Allows ulcer to heal from within

MUCOSAL DEFENSE ENHANCERS

Sucralfate (Carafate) Binds selectively to ulcerated mucosa and forms a barrier Protects ulcer from acid and pepsin Allows ulcer to heal from within Adverse effects: constipation Separate doses of this and antacids by 2 hrs Other PUD Drugs Sucralfate (Carafate) Effective with minimal side effects and lack of significant drug interactions Mechanism of action Pharmacokinetics Therapeutic uses Adverse effects Drug interactions Preparations, dosage, and administration Note: Pepto-bismol is a bismuth based agent that acts to assist the mucus layer protection of the stomach. Using this drug will lead to darkening of the stools which can mimic melena. Bismuth also shows up on x-ray. The agent misoprostol (Cytotec) is rarely used any more because of adverse effects. It is a prostaglandin type agent that contributes to the mucus protection. This chart shows OTC meds available for PUD treatment including the neutralizing antacids:

Bismuth (Pepto-Bismol) Sucralate (Carafate)

D. Inflammatory Bowel Disease 1. Consists of Ulcerative Colitis and Crohns disease 2. There are many similarities between these two disorders and also a few important differences. The following chart is helpful in delineating these differences

Comparison of Ulcerative Colitis and Crohn's Disease

Feature
Distribution Rectum Depth of Inflammation

Ulcerative Colitis
Diffuse, distal predominance Always involved Mucosal

Crohn's Disease
Segmental or diffuse, often proximal predominance ILEAL INVOLVEMENT Often spared Often focal Transmural Often present Often present Often present FISTULA FORMATION

Microscopic Distribution Diffuse

Sinus Tracts and Fistulae Absent Strictures Granulomas COMPLICATIONS Absent Absent Toxic Megacolon

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Ulcerative Colitis Information regarding the etiology of IBD:

Crohns Disease

The causes of ulcerative colitis and Crohn's disease are not known. However, a reasonable hypothesis for the pathogenesis of inflammatory bowel disease can be presented. As yet unidentified antigens, possibly a mycobacterium, paramyxovirus, or components of cigarette smoke, activate resting macrophages to release a wide variety of cytokines. 3 Cytokines is a collective term for a group of low-molecular-weight peptides that are active at low concentrations and bind to specific receptors to produce autocrine, paracrine, and endocrine effects. The most abundant cytokine is interleukin-1 (IL-1), which not only causes diarrhea but also acts as a pyrogen. Other cytokines activated in the inflammatory process are IL-6, tumor necrosis factor a (TNF-), and the chemokine IL-8. Cytokines cause differentiation of lymphocytes to different types of T cells. Helper T cells, type 1 (Th-1), are associated principally with Crohn's disease, whereas Th2 cells are associated principally with ulcerative colitis. These cytokines serve to stimulate the immune system and cause an inflammatory reaction, thus producing tissue damage in the intestinal mucosa.

This is a summary from this URL: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/inflam matory-bowel-disease/ Summary

Ulcerative colitis is characterized by mucosal inflammation of the colon, whereas Crohn's disease is characterized by transmural inflammation involving any part of the gastrointestinal tract. The diagnosis of ulcerative colitis or Crohn's disease is based on a constellation of positive endoscopic, radiographic, and histologic findings, with negative stool cultures. The differential diagnosis of irritable bowel syndrome includes infectious colitis, celiac sprue, intestinal lymphoma, radiation enteropathy, NSAID use, and ischemic colitis. First-line therapy for ulcerative colitis patients includes 5-aminosalicylic agents, and some patients also may need corticosteroids, immunosuppressives, and biologic agents. First-line therapy for Crohn's disease patients often includes budesonide, and some patients also may need other corticosteroids agents, immunosuppressives, antibiotics, and biologic agents. Colorectal cancer risk is an important concern for patients with ulcerative colitis or Crohn's colitis.

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The 5-aminosalicylic agents include: Oral Aminosalicylates Sulfasalazine (Azulfidine) Rectal Aminosalicylates Mesalamine

These agents are actually useful in both Crohns and UC. The treatment approach for IBD is a stepped approach and is well documented in this image:

E. Portal Hypertension the sections in the GI DISORDERS handout regarding Portal HTN / Ascites / Hepatic Encephalopathy / Jaundice are concise and outline the material well. I will not redo that here. F. Viral hepatitis 1. There are many types of viral hepatitis. They are pretty much all categorized by marked elevation of the liver enzymes (AST and ALT) and bilirubin levels. Most hospitals have a lab panel called a liver or hepatic profile that consists of these measurements. The panels may also include a few other values like Alkaline phosphatase and GGT (gamma-glutamyl transferase). Elevation of these substances can also occur in viral hepatitis, but can also occur in a number of other conditions. 2. For our purposes, we will focus on types A, B and C. a. Type A is mostly transmitted by the food borne route (ie. fecaloral transmission). In almost all cases, Hep A is self limiting (goes away on its own with supportive treatment) and does NOT result in Chronic hepatitis. Outbreaks of this type of hepatitis frequently occur secondary to tainted food supplies and/or poor hygiene by food service workers. b. We will look at types B and C together. there are a few differences, but for the most part they have similar courses. These types of viral hepatitis are primarily transmitted venereally (through body fluids). These types of viral hepatitis are associated with promiscuity, unprotected sex and IV drug use. They can also be transmitted via poorly screened blood that is transfused. Both type B and C can lead to Chronic hepatitis with subsequent hepatic failure. Liver

12 cancer risk is also markedly increased in patients with types B/C. Most hospitals have a Viral Hepatitis Profile which is used to characterize the specific type of viral hepatitis that is present in a given patient. It should be noted that IgG antibodies, when present alone, do not signify acute disease. The presence of IgG antibodies, in the absence of other types, usually signifies past disease or HEP B vaccination. The presence of IgM antibodies along with other specific antibodies signifies acute disease. Treatment for chronic viral hepatitis involves immune suppressive therapy and Interferon alpha. Interferon is a type of cytokine released from lymphocytes that has anti-viral properties. It is given parenterally, very expensive and frequently causes severe flu-like adverse effects. Patients often become noncompliant due to these factors. The most aggressive form of therapy is liver transplant. This surgery is plagued with many issues. The patients who are to be considered must demonstrate documented sobriety for at least six months and usually a year. After successful documentation is received, the patient is then out on the transplant list. The waiting period is often lengthy and the patient frequently worsens during this period and/or relapses on alcohol and/or drugs. The above information regarding viral hepatitis is sufficient, the other information in the power point outline can be ignored for now. Regarding Cirrhosis, alcoholic cirrhosis, cholelithiasis, cholecystitis and pancreatitis (acute), the information in the outline does not need to be repeated here. I will list a few important points however: 1. On physical exam, the patient with cirrhosis will have a very small NONPALPABLE liver. 2. Remember that patients with end stage liver disease have clotting issues (elevated PT/INR) due to insufficient production of clotting proteins. They will also be globally edematous secondary to markedly decreased oncotic pressure. This occurs secondary to inability of the diseased liver to produce albumin. 3. Almost all gallstones are made of precipitated and crystallized cholesterol. 4. Remember that these patients often demonstrate an exacerbation of their symptoms after a meal containing lipids. They may also have right scapular pain that is referred. Treatment is almost always laparoscopic cholecystectomy. 5. Acute pancreatitis is most commonly due to alcoholism or cholelithiasis. It presents as severe mid-epigastric pain often associated with vomiting. Diagnosis is usually made when a patient presents with the previously discussed risk factors

13 and symptoms combined with elevated serum Lipase and Amylase. Treatment involves gut rest usually maintained with an Ng tube hooked up to suction, followed by a slow advancement of their diet. Recurrent acute pancreatitis can result in chronic pancreatitis, which is associated with significant morbidity and mortality. Regarding the anti-emetic drugs, refer to this list :

Promethazine (Phenergan)
Promethazine is also known as phenergan and mepergan. It is also used to treat motion sickness, reduce allergic symptoms, and for sedation. It is one of the drugs of the phenothiazine type. In addition to other qualities, it is an antihistamine. Promethazine is given in doses of 12.5 to 25 mg every 4 hours if injected into the muscle or as a suppository. As a syrup, 25 mg should be given every 4 to 6 hours. Doses for children vary by age, weight, and severity of condition. Patients taking promethazine may experience a large number of side effects, including drowsiness, ringing in the ears, a lack of coordination, problems with vision, fatigue, euphoria, nervousness, tremors, seizures, a catatonic-like state, and hysteria. These effects are usually reversible. At high doses, patients may also exhibit extrapyramidal reactions. Extrapyramidal reactions can briefly be described as agitation (jitteriness, sometimes insomnia), muscle spasms, and/or pseudo-Parkinson's (a group of symptoms including, but not limited to, drooling, tremors, and a shuffling gait).

Prochlorperazine (Compazine)
Prochlorperazine is also known as compazine. Like promethazine, it is a member of the class of phenothiazines. Unlike promethazine, however, prochlorperazine also belongs to the class of drugs known as antipsychotics, or neuroleptics. Antipsychotic drugs are used to treat psychoses and other psychiatric disorders. In addition to its use as an antiemetic and anti-psychotic drug, prochlorperazine is also used to treat non-psychotic anxiety. Generally, the dose is 5 to 10 mg, 3 to 4 times per day. However, the effect of medication varies widely from patient to patient, so the dose should be tailored to each individual. Prochlorperazine is available as a syrup, tablet, 25 mg slow-release capsule, and in injectable form. Prochlorperazine has many side effects, including low blood pressure, dizziness, blurred vision, skin reactions, and jaundice. Two other (rare) disorders, tardive dyskinesia and neuroleptic malignant syndrome (NMS), are also associated with antipsychotic drug use. Serotonin Receptor Antagonists The serotonin receptor antagonists include granisetron (kytril), dolasetron (anzemet), and ondansetron (zofran). These drugs are used for postoperative nausea and emesis as well as nausea and vomiting associated with chemotherapy, and are often used in combination with a corticosteroid. Ondansetron is approved for nausea and vomiting associated with radiation therapy. The use of these agents in the treatment of nausea not associated with surgery and/or chemotherapy is becoming more common. These agents antagonize serotonin receptors directly within the hypothalamic emesis center. They are often

14 effective in cases where phenergan and/or compazine are not effective. The major drawback of these agents is cost. The primary information that I want you to be aware of concerning the anti-emetics is the category of drug (eg. phenothiazine), primary adverse effects and the fact that phenergan and compazine are much lower in cost compared to Zofran and other serotonin drugs. Laxatives regarding the laxatives, know the four primary types, how they work and an example of each. This information is found in the GI outline and can be further reinforced here: http://en.wikipedia.org/wiki/Laxative Anti-diarrheal agents both agents that are commonly used to control diarrhea are opiate derivatives. Remember that opiate pain medications generally have constipation as a side effect. The two agents are Diphenoxylate (Lomotil) and Loperamide (Imodium). For some reason, these are listed in the outline as non-opioids.but that is not accurate. These agents will sometimes lead to positive results for opiates on a drug screen. Musculoskeletal / Rheumatologic Pathophysiology and Pharmacology Notes on normal anatomy and physiology: 1. Remember that bone is in general a very vascular and metabolically active tissue. It serves as a repository for calcium and phosphorus. Osteocytes are mature bone cells. Osteoblasts build bone, and osteoclasts break it down. 2. Long bones (such as the femur) have three main sections. The ends of the bone are lined with articular cartilage and are called the epiphysis. The shaft is called the diaphysis and between those two sections, one finds the metaphysis, also known as the growth plates. By the time one reaches their early twenties (or before), the metaphyseal regions are completely calcified. 3. Most joints in the body fall into one of two categories. Either they are non-synovial (like the skull joints) or synovial (knees, hips, elbows, fingers, etc). The synovial joints are characterized by the presence of synovial capsules surrounding the joint and containing synovial fluid. This fluid acts as lubrication.

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These joints are more flexible then non-synovial joints and provide more protection and cushion then non-synovial joints. The downside is that the synovial tissue is the tissue attacked in patients with rheumatoid arthritis. 4. Healing bone (after a fracture) forms a CALLUS around the fracture site. This is the only term that you need to understand from this page. 5. Remember that muscle tissue contracts secondary to actin sliding over myosin. It takes energy, in the form of ATP, to relax after contraction. This is why patients who expire have a period of Rigor Mortis. No lifeno ATP..no muscle relaxation. Also, muscle uses creatinine phosphate as an energy carrier, in addition to ATP. FRACTURES A fracture is another term for a broken bone. There is NO difference between a fracture and a break. Some fractures are COMPLETE meaning that extend through the cortex on both sides of the diaphysis.some fractures are termed GREENSTICK FRACTURES, meaning that they extend through only one side of the cortex (similar to trying to break a branch of a tree that is still living). Another term(s) that describes the character of a fracture is simple (closed) or compound (open). Fractures that are termed open are exposed to the outside world through a break in the skin surface. An open fracture is considered an orthopedic emergency. They absolutely need to be evaluated by an orthopedic surgeon. Most of the time, these patients will go to the OR to have the fracture site cleaned and repaired. Obviously the biggest risk in this situation is infection. In the evaluation of ANY extremity injury (fracture, dislocation, laceration, etc...), THE FIRST THING THE NURSE MUST DO IS EVALUATE FOR NEUROVASCULAR INTEGRITY DISTAL TO THE INJURY. Feel for pulses and make sure that the patient has intact motor and sensory function. This evaluation is critical as a patient with impaired neurovascular integrity will require IMMEDIATE intervention. This evaluation

16 will also most likely be ordered every few hours after the injury is repaired. Again, if the limb was neurovascularly intact after repair of the injury and now is not....This requires IMMEDIATE evaluation. Damage to the nerve and/or limb ischemia can lead to permanent disability if not recognized and treated immediately. Regarding the types of fractures, here are a few notes in addition to the information found on the power point outline (which is also up on sonis). 1. As noted, a COMMINUTED fracture means that there are MORE THEN TWO bone fragments. When somebody says, I shattered my ankle...this is what they mean. Here are some images of different types of fractures:

2. A torus fracture., also called a buckle fracture is seen primarily in children. The cortex of their bone is not fully calcified and therefore it is soewhat elastic in nature. When a fracture occurs, the cortex buckles out instead of completely fracturing into two fragments. Here is an image of TORUS fracture of the radius:

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Sometimes, you can not even make out the fracture line, you only see evidence of a buckle as you follow the cortex. These can missed easily if you do not know what to look for. I should also note here that when evaluate bony injuries in children, it can be very difficult to tell the difference between a fracture and an incompletely ossified metaphysis. One trick is to order the same x-ray view of the unaffected limb and compare them. If you see additional lines on one side...it is probably a fracture. This is a NORMAL x-ray of a childs elbow:

18 You can see how difficult it might be to differentiate a fracture from a normal nonossified growth plate. 3. Spiral fractures require a twisting mechanism of injury to occur. If one notes a spiral fracture in a child with a history not consistent with a twisting motion, for example, if the parents state that the child fell off the couch, and there x-ray looks like this:

It is considered CHILD ABUSE...until proven otherwise. All suspected abuse HAS TO BE EVALUATED. Children services will usually be called. This is a very difficult situation, especially if there is no abuse....but more often then not....a spiral fracture accompanied by a history not consistent with a twisting motion....means abuse! This image shows the different types of fractures very well:

4. A PATHOLOGIC fracture means that a fracture occurs without an appropriate amount of force to produce such fracture. In other words, the fracture would not

19 have occured if there was not underlying bone disease (eg. osteoporosis, bony tumor,etc...). When you here of an elderly lady who broke her hip by just getting out of bed...this implies a pathologic fracture. One can see a fracture in the midtibia here. There is an underlying tumor, which weakened the bone and made it possible for a fracture to occur without the force that would be required if the bone was not diseased:

5. A STRESS fracture is often very subtle and occurs due to repeated stress at a specific anatomic location. For example, an athlete who is training for a marathon and runs several miles per day on hard surface may suffer a strees fracture to one of the metatarsals:

Many times the only way to diagnose a stress fracture is to obtain a nuclear bone scan. In this test, the patient is injected with nuclear contrast material that will

20 show up under a nuclear camera. It will LIGHT UP in areas where there is increased metabolic activity like a healing fracture or a malignancy. This bone scan shows a stress fracture of the calcaneus that did not show up on plain xray:

You can obviously see how the calcaneus lights - up. Dislocation / Subluxation The difference between these two terms is that a subluxation implies that the bone that is displaced from the joint is still partially in contact with the joint. A dislocation implies that there is no contact between the displaced bone and the joint. In the real world, these terms are often confused and used interchangably. Many times chiropracters will use the term subluxation to imply that there has been some movement between the articulating surfaces (articulating means that they are forming a joint). This may or may not be accurate...and many times the angle that they point out to the patient is perfectly normal....but just looks angled. Like any profession, there are good ones and bad ones....just be careful. This is an x-ray of a complete dislocation of a shoulder:

You can see how the head of the humerus is completely out of the glenoid joint. This is a subluxation of the same joint:

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You can see that is some contact (albeit minimal) between the humerus and the joint. Remember, as with any limb injury, the first thing that must be done on initial evaluation of a patient with a suspected dislocation or subluxation, is to evaluate the limb distal to the injury for neurovascular integrity. If you are the primary evaluating person, always get an x-ray of a suspected dislocation/subluxation, even if the patient states that this has happened many times before, becuase occasionally a fracture can occur ALONG WITH a dislocation. If you try to reduce the dislocation (put it back into place) and there is an associated fracture...you can cause permenant damage. Also, I should state here, that the term REDUCTION implies either putting a dislocated bone back into the joint or aligning the fragments of a fractured bone before casting it. In regards to the fracture, the reduction can either be described as an open reduction or a closed reduction. The difference is that in an open reduction, the patient is taken to the operating room and surgical reduction is required (usually with the placement of pins or a plate or wire to hold it in place). Most fracture reduction are of the closed type and are done without surgery, although conscious sedation may be required. When you look at the chart of many nursing home residents, especially females, you will see this as part of there history: ORIF right or left hip. This is an abbreviation for Open Reduction with Internal Fixation and is very common in patients who have had a hip fracture. Sprains and Strains There is technically a difference between these terms, but in the real world they are used interchangably. Therefore, you do not need to differentiate between them. You should, however, know the difference between a ligament and a tendon. Often, a severe sprain can more difficult to heal then a fracture. For

22 example, the ligaments on the outside of the ankle, called the deltoid ligaments, are so strong, that when the ankle is inverted (twisted with the plantar surface of the foot pointing medially), the distal part of the tibia is avulsed (torn away) rather then the ligament tearing. In this x-ray, you can see that the tip of the tibia is avulsed from the shaft:

The treatment of sprains and strains can be summarized by the word RICE (REST, ICE, COMPRESSION and ELEVATION). Most of the time, we do not rest the injury long enough and it remains unstable for life....and will become sprained even with minimal force. Remember also, that NSAIDs are very helpful in the treatment of these injuries. One should use them on a scheduled basis for 3 - 5 days. This builds up a blood level and will help to relieve the swelling. Using them only PRN for pain does not really acheive this. OSTEOPOROSIS This disease of bone mineralization is very common. It occurs much more frequently in women as they require a certain level of estrogen to mineralize their bones. This is a good basic summary of osteoporosis: Osteoporosis, which means "porous bones," causes bones to become weak and brittle so brittle that even mild stresses like bending over, lifting a vacuum cleaner or coughing can cause a fracture. In most cases, bones weaken when you have low levels of calcium, phosphorus and other minerals in your bones.

23 A common result of osteoporosis is fractures most of them in the spine, hip or wrist. Although it's often thought of as a women's disease, osteoporosis also affects many men. And aside from people who have osteoporosis, many more have low bone density. This is a good summary of causes: Throughout ones lifetime, old bone is removed (resorption) and new bone is added to the skeleton (formation). During childhood and teenage years, new bone is added faster than old bone is removed. As a result, bones become larger, heavier, and denser. Bone formation outpaces resorption until peak bone mass (maximum bone density and strength) is reached around age 30. After that time, bone resorption slowly begins to exceed bone formation. For women, bone loss is fastest in the first few years after menopause, and it continues into the postmenopausal years. Osteoporosiswhich mainly affects women but may also affect menwill develop when bone resorption occurs too quickly or when replacement occurs too slowly. Osteoporosis is more likely to develop if you did not reach optimal peak bone mass during your bone-building years. RISK FACTORS:

Risk factors you cannot change:

Gender. Your chances of developing osteoporosis are greater if you are a woman. Women have less bone tissue and lose bone faster than men because of the changes that happen with menopause. Age. The older you are, the greater your risk of osteoporosis. Your bones become thinner and weaker as you age. Body size. Small, thin-boned women are at greater risk. Ethnicity. Caucasian and Asian women are at highest risk. African American and Hispanic women have a lower but significant risk. Family history. Fracture risk may be due, in part, to heredity. People whose parents have a history of fractures also seem to have reduced bone mass and may be at risk for fractures.

Risk factors you can change:

24 Sex hormones. Abnormal absence of menstrual periods (amenorrhea), low estrogen level (menopause), and low testosterone level in men can bring on osteoporosis. Anorexia nervosa. Characterized by an irrational fear of weight gain, this eating disorder increases your risk for osteoporosis. Calcium and vitamin D intake. A lifetime diet low in calcium and vitamin D makes you more prone to bone loss. Medication use. Long-term use of glucocorticoids and some anticonvulsants can lead to loss of bone density and fractures. Lifestyle. An inactive lifestyle or extended bed rest tends to weaken bones. Cigarette smoking. Smoking is bad for bones as well as the heart and lungs. Alcohol intake. Excessive consumption of alcohol increases the risk of bone loss and fractures.

This Site has an excellent summary...I will not copy it here: http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/default.asp

Important: 1. Prevention involves adequate calcium and vitamin D intake, especially during the pre-menopausal years in women. 2. Pathologic fractures and vertebral compression fractures are very common in patients with osteoporosis. Multiple vertebral compression fractures can cause kyphosis (dowagers hump) in women and height loss.

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COMPRESSION FRACTURES:

Kyphosis:

3. A bone density test (non-invasive) is used to diagnose osteoporosis:

26 This produces a report which compares the patients results to normalized values and also, over time, allows one to compare their density with previously done tests. The most common agents used in the treatment of osteoporosis are shown in the following table:

How It Works Bisphosphonates are antiresorptive medicines, which means they slow or stop the natural process that dissolves bone tissue, resulting in maintained or increased bone density and strength. 1 This may prevent the development of osteoporosis. If osteoporosis already has developed, slowing the rate of bone thinning reduces the risk of broken bones.

27 Biphosphanates should not be used by non-ambulatory patients. After taking these medicines, one should move around for awhile to prevent the medication from being in contact with the same stomach area for an extended period of time as this can cause erosion and ulcer symptoms. These medications are also indicated for Pagets disease, which is a disease of impaired bone remodeling. It is not very common, but does appear on exams (not just mine). So remember to associate Pagets disease with the word remodeling.

This x-ray of the leg bones in a paget with long term Pagets disease shows obvious problems with bone mineralization and remodeling:

There are currently some new treatments for vertebral compression fractures that involve the injection of an acrylic like material into the vertebrae to restore height. Pain secondary to the fracture is usually decreased as well.

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Occasionally calcitonin is used to treat osteoporosis. Osteomyelitis is the term for bone infection and used to be much more common then it is now. More soldiers died of this then anything else during the civil war. This pathology is much more common in patients with vascular perfusion impairment...like those with diabetes. Patients with long term skin and soft tissue infection can develop osteomyelitis as the infection spreads to the bone. These infections are often very hard to eradicate and usually require at least 6 weeks of IV antibiotics. This is frequently done at home using a long term central venous catheter (PIC line) and home health care nurses. Here are a few images of osteomyelitis:

On bone scan:

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In the OR:

Osteoarthritis Osteoarthritis Also called Degenerative joint disease or wear and tear arthritis Noninflammatory Does not involve synovia Risk factors include age , prior trauma and genetics Primary defect is loss of articular cartilage Symptoms include pain and stiffness Diagnosis is made via H+P and xray studies Treatment includes NSAIDs, Tylenol and surgery * This type of arthritis is much more common then rheumatoid arthritis * This is the type of arthritis that one gets from chronic strain to a particular joint. * Remember...it is non-inflammatory....anti-inflammatories may help the pain, but they will not change the course of disease * This is the type of arthritis that one frequently hears the phrase, bone on Bone in the description of the xray findings. This means that the articular cartilage is completely worn away and the joint space is markedly

30 reduced. This finding associated with pain and/or disability usually precedes joint replacement surgery. This is good xray image:

Rheumatoid Arthritis Autoimmune destruction of synovial joint structures Affects all age groups, although in pediatric group, called Juvenile RA(Stills Disease) More common in females Symptom include: Joint pain, stiffness and swelling Systemic symptoms such as fever, rash, malaise, Raynauds phenomena Joint deformity Rheumatoid nodules Treatment includes: Rest Hot/cold packs Physical Therapy NSAIDs and/or Corticosteroids DMARDs (disease modifying anti-rheumatoid drugs)

31 Surgery As noted above, this type of arthritis is of autoimmune etiology. There IS significant swelling of the affected joints. Systemic symptomatology is also seen very commonly. This includes fever, rash, night sweats, LAD and others. The blood work will show evidence of marked generalized inflammation such as an elevated ESR (erythrocyte sedimentation rate)...also known as a sed rate. Patients frequently also have a positive test for Rheumatoid Factor (RF) in there blood, although not all patients with RA have RF. This disease freqeuntly leads to long term bone and joint deformities and disability. Here is an image showing swelling of the synovial membrane:

These images show common upper extremity deformities on x-ray and externally (ignore the fact that rheumatoid is spelled wrong on the lower image!):

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Treatment of RA involves the use of anti-inflammatory agents (steroids and NSAIDs), immune suppresants and agents that are classified as DMARDs (disease modifying anti-rheumatoid drugs). This last category will help slow down the progression of the disease, but most of the agents are expensive, injectable and associated with adverse effects.

This is brief summary of a few of the DMARDs:

Traditional DMARDs can be grouped in different categories and include: Anti-malaria medications, particularly Plaquenil Arava Organ antirejection drugs, such as cyclosporine Miscellaneous drugs, such as Azulfidine and gold Chemotherapy drugs, such as methotrexate, Imuran, and Cytoxan

Here is a little specific information on some agents specifically:

Gold Gold has been used as a medical treatment for centuries and was a mainstay of RA treatment from the 1920s to the mid 1980s. Currently it is a rarely used treatment for RA as newer medications are more effective.

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Gold works by decreasing inflammation in the joints, although doctors don't know how it does this. Gold is given orally or by injection into the muscle. The injection is more effective than the oral version. Possible side effects include skin rash, anemia, low white blood cell count, or liver and kidney problems. Methotrexate The most commonly used DMARD is methotrexate. Since the early 1980s, methotrexate has gained prominence as an effective treatment for RA. It also has advantages in having dose flexibility, as higher doses may be used for worse disease, and it is easy to monitor for side effects by testing for liver function and blood counts. Side effects of methotrexate include rash, mouth sores, hair loss, fatigue, liver inflammation, and bone marrow toxicity. The risk of side effects can be reduced by taking daily folic acid. Imuran Imuran (azathioprine) is a chemotherapy drug that can be effective for RA, particularly for complications such as vasculitis. It is an oral tablet. Side effects include nausea, vomiting, rash, mouth sores, liver and blood count abnormalities, and increased risk of infection. Regular blood test monitoring is mandatory. Anti-malaria Drugs (Plaquenil) Plaquenil (hydroxychloroquine) is a drug used to treat malaria. It was discovered that it worked for arthritis when people taking the drug for malaria reported improvements in their arthritis. The drug affects the immune system, although doctors do not know precisely how it works to improve rheumatoid conditions. Usually Plaquenil is used when other RA treatments fail. It can be given along with steroid treatment to reduce the amount of steroid needed. It is also given to treat the facial rash of lupus. Plaquenil is given by mouth daily. Side effects include low white blood cell counts, blood or protein in the urine, nausea, and skin rashes. High doses can rarely cause injury to the back of the eye (retina); therefore, patients on this drug should see an eye doctor every six to 12 months.

34 The newest class of drugs used in the treatment of RA are the Biological Response Modifiers. Most of these agents interfere with the action of inflammatory mediators like Tumor Necrosis Factor (TNF) and others:

Biologic response modifiers Biologic response modifiers, also known as biologics, are medications that were designed to prevent or reduce the inflammation that damages joints. Biologics target molecules on cells of the immune system, joint, and the products that are secreted in the joint, all of which can cause inflammation and joint destruction. There are several types of biologics, each of which targets a specific type of molecule involved in this process (tumor necrosis factor, interleukin-1, and cell surface molecules on T and B lymphocytes). (See "Overview of biologic agents in the rheumatic diseases"). Biologics that bind tumor necrosis factor (TNF), called antiTNF treatments, include Etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade). These are called anti-TNF agents. Anakinra (Kineret) inhibits interleukin-1. Anakinra is significantly less potent than TNF inhibitors in most people with rheumatoid arthritis. It is occasionally recommended for selected individuals who do not respond to anti-TNF agents. Anakinra cannot be used at the same time as antiTNF agents due to the risk of infection. Abatacept (Orencia) interferes with the activation of T cells. Abatacept is usually recommended only for people with moderate or severe rheumatoid arthritis that is not controlled with methotrexate and an anti-TNF agent. (See "T cell targeted therapies for rheumatoid arthritis"). Rituximab (Rituxan) depletes B cells. Rituximab is usually recommended only for people with moderate or severe rheumatoid arthritis that is not controlled with methotrexate and an anti-TNF agent. (See "Rituximab and other B cell targeted therapies for rheumatoid arthritis").

35 Summary of primary points: 1. RA is a systemic autoimmune disease that is characterized by immune and inflammatory destruction of the synovial tissue. 2. It often lead to significant deformity and disability 3. Systemic symptoms are frequently present 4. Treatment involves the use of steroids, NSAIDs, DMARDs and Biologic response modifiers. Ankylosing Spondylitis This disease is not very common, but when you see a patient with it...you will not forget them. This disease eventually causes complete calcification of the intervertebral discs, leading to an inability to bend over at all. The spine deformity as seen radiographically is termed, bamboo spine. Chronic, inflammatory disease involving fusion of the joints of the spine and sacroilium Genetic basis (HLA-B27) More prevalent in men Here is a radiographic image of the lower spine:

Note how the intravertebral discs are as dense as the vertebrae themselves. So, in summary, Ankylosing spondylitis is a genetic disease seen usually in young males. The genetic marker that is tested for is called HLA - B27. This test is specific for this disease. Finally, calcification of the inter-vertebral discs is the primary symptomatic pathology.

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GOUT Arthritis caused by precipitation of uric acid in the joint structures Uric acid deposits called Tophi Seen more frequently in males Uric acid comes from metabolism of purines Trauma is aggravating factor Clinical Manifestations: Hyperuricemia Gouty arthritis Tophaceous gout (crystal deposition) Renal Calculi Most common joint involved is the metatarsophalangeal joint of the great toe

Treatment: NSAIDs Allopurinol (lowers uric acid levels) Colchicine Corticosteroids Narcotics Patients with gout usually have elevated serum uric acid, but not always. This is an image of acute gout in the MTP joint of the great toe:

Pretty....isnt it?! You can see why this is very painful. The diagnosis is usually made on history and physical alone. Rarely, aspiration of the affected joint is required. If this

37 aspirate contains uric acid crystals, they will look like this under a polarizing microscope:

The treatment of gout involves both acute and prophylactic treatment. Prophylactically, in patients with chronically elevated serum uric acid levels, we will use a drug called allopurinol (Zyloprim ). This drug is taken orally,

usually two to three times per day. This drug acts by inhibiting enzymes in the uric acid production pathway...thus leading to decreased serum uric acid. The acute treatment of gouty attacks involves NSAIDs (frequently a very old one called Indomethacin (Indocin ). This agent is often combined with another drug that has been around for quite a while called Colchicine. The dosing of this agent is unusual. Usually we have the patients take two tablets followed by one every hour until diarrhea starts. They then stop and repeat the process in about twelve hours. Rarely, colchicine can cause Aplastic Anemia, which is complete bone marrow suppresion. If the patient notices bruising or bleeding...they need to be seen and tested immediately.
Fibromyalgia Fibromyalgia Characterized by diffuse musculoskeletal pain, fatigue and trigger points Much more common in women Etiology unknown Diagnosis made when all other differential diagnoses are rules out (see Table 41-8, pg. 1401)

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Treatment: NSAIDs Rest / exercise Tricyclics Fibromyalgia is a very controversial diagnosis. As noted, there is no specific test for this disorder. The diagnosis is usually made when all other disorders have been ruled out. This disorder is most likely a combination of different disorders with the commonality of trigger point muscle pain and fatigue. In some patients, there may be associated psychiatric issues like depression...although this can not be said for all patients with fibromyalgia. For those interested, this is an excellent, up to date summary of this disorder: http://www.mayoclinic.com/health/fibromyalgia/DS00079 Finally, I want to discuss hormone replacement therapy (HRT) in postmenopausal women and the controversial issues surrounding it. First of all...lets look at estrogen and its role in female physiology:

Estrogen contributes to the development of secondary sex characteristics, which are the defining differences between men and women that dont relate to the reproductive system. In women, these characteristics include breasts, a widened pelvis, and increased amounts of body fat in the buttock, thigh and hip region. Estrogen also contributes to the fact that women have less facial hair and smoother skin then men. Estrogen is an essential part of a womans reproductive process. It regulates the menstrual cycle and prepares the uterus for pregnancy by enriching and thickening the endometrium. Two hormones, the luteinizing hormone (LH) and the follicle stimulating hormone (FSH), help to control how the body produces estrogen in women who ovulate. Estrogen is manufactured mostly in the ovaries, by developing egg follicles. In addition, estrogen is produced by the corpus luteum in the ovary, as well as by the placenta. The liver, breasts and adrenal glands may also contribute to estrogen production, although in smaller quantities. Estrogen can be broken down into three distinct compounds: estrone, estradiol and estriol. During a womans reproductive life, which starts with the onset of menstruation and continues until menopause, the main type of estrogen produced is estradiol. Enzymatic actions produce estradiol from

39

androgens. Testosterone contributes to the production of estradiol, while the estrogen estrone is made from andostenedione.
Now...progesterone:

Progesterone is sometimes called the "hormone of pregnancy",[25] and it has many roles relating to the development of the fetus: Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the vaginal epithelium and cervical mucus, making the mucus thick and impermeable to sperm. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to menstruation. Normal menstrual bleeding is progesterone withdrawal bleeding. During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy. Progesterone decreases contractility of the uterine smooth muscle.[25] In addition progesterone inhibits lactation during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production. A drop in progesterone levels is possibly one step that facilitates the onset of labor.

The fetus metabolizes placental progesterone in the production of adrenal steroids.

This explains why progesterone only oral contarceptive pills (OCPs) work. They basically fool the body into believing that it is pregnant.

The use of postmenopausal hormone replacement therapy (HRT) has changed markedly over the last ten years. About eight years ago, two major studies were done that showed that HRT is associated with a marked INCREASE in the frequency of strokes and cardiac events. Prior to that, it

40 was believed that HRT protected women from cardiovascular disease and stroke. Now, the decision to place a woman on HRT depends on developing an individualized risk/benefit profile for that patient. The potential benefits of HRT are relief of vasomotor symptoms (hot flashes), mood fluctuations and vaginal atrophy and/or dryness. Also, there is some protection given against the worsening of osteoporosis. So, in summary, one must weigh these potential benefits against the potential risks in light of the degree of the patients symptoms and how much they interfere with her life, the family risk of MI and CVA, smoking history and osteoporosis prevalence in the family. RENAL / UROLOGIC PATHOPHYSIOLOGY and PHARMACOLOGY

Kidney Stones Kidney Stones (also called urolithiasis and nephrolithiasis) relatively common problem seen more frequently in men than women. Stones can be formed out of many different substances, however in order of frequencythese are the most common: Calcium Oxalate (and other salts of calcium) - > 75% Struvite bacterial products that harden Uric acid usually in patients with high serum levels of uric acid like patients with Gout. When a stone acutely obstructs the flow of urine (in the ureter), this causes intense pain. Difficulty urinating may also occur. Acute symptoms include lower abdominal pain (frequently radiating to the groin and back), hematuria and diaphoresis. A patient who develops kidney stones will often have reoccurrences. The most common methods of making the diagnosis are helical CT scan and/or an intravenous pyelogram (IVP). In the IVP, the patient is injected with x-ray contrast material (usually iodinated) and xray images are obtained at several intervals after the contrast is administered. Images are obtained from several different angles as well. Obstruction of a ureter usually appears as Hydroureter ( a large dilated ureter) and/or hydronephrosis (a large dilated kidney).

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Once the diagnosis is made, treatment depends upon the size and location of the stone. Most stones less then 5mm will be passed without need for intervention. Depending on many factors, the patient can be treated in the hospital or at home. They are instructed to drink lots of water, take pain medicine as prescribed and strain the urine. This is done in order to chemically evaluate the stone and then provide preventive therapy depending on the underlying issues. If the stone is not passed or the pain is severethe urologist will surgically retrieve the stone. A stent is then placed in the ureter to prevent further obstruction due to spasm. This is removed after 4 to 6 weeks. Chronic obstruction of urine flow will lead to chronic kidney infection and eventual renal failure.

Vasovagal syncope (or idiopathic orthostatic hypotension) this is a condition that occurs infrequentlybut usually affects females less then 30 years of age. They have dizziness and light headedness that arises when they stand up. This may lead to frank syncope. This condition is usually diagnosed after a long work-up looking for more common disorders. The test used to make this diagnosis is called the Tilt Table Test. This changes the patients body position and they are assessed for the development of symptoms as described and changes in vital signs. Once diagnosed, patients are often treated with a medication called:

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Fludrocortisone (Florinef) - Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions. The consequence of these three primary effects together with similar actions on cation transport in other tissues appear to account for the entire spectrum of physiological activities that are characteristic of mineralocorticoids. In small oral doses, fludrocortisone acetate produces marked sodium retention and increased urinary potassium excretion. It also causes a rise in blood pressure, apparently because of these effects on electrolyte levels. In summary, this medication increases the intravascular volume by increasing NA+ and H20 retention (like aldosterone), and this improves cerebral perfusion when standing.

Know the major indications and adverse effects for the antibiotic metronidazole (FLAGYL) Interferon alpha is an agent that occurs naturally as a cytokine (interleukin). We use it to treat chronic viral hepatitis. It often produces severe and debilitating flu-like adverse effects. Know the indications, mechanism of action and adverse effects associated with the statin drugs like lovastatin (Mevacor) Know the indications, mechanism of action and adverse effects associated with nitroglycerine. Understand the major differences in bacterial coverage between the first generation and later generation cephalosporins Repeating the information listed on the previously distributed Final Exam Study Guide, make sure that you review the cardiovascular material including: o inotropes and chronotropes (what they are and some examples of eac h) o Goals of treatment for CHF o Basic issues regarding the use of Digitalis o Ace inhibitors and ARBs o Basic issues concerning the diuretics (HCTZ, K+ - sparing and loop diuretics) o Use of warfarin (Coumadin ) and Heparin (non-fractionated and lovenox) o Differential diagnosis of chest pain o Angina and MI presentation, diagnosis (including serum tests and EKG findings) and basic treatment Side effects of tetracycline

43 Pulmonary physiology, disorders, diagnosis and treatment o COPD o PFTs o Asthma (including prophylactic and acute treatment) o - 1 antitrypsin deficiency o Pulmonary embolus Basic facts regarding Anemia: defined as a condition that results in impaired oxygen carrying capacity and delivery of blood. General symptoms include fatigue, SOB, pale skin There are many different types and etiologies For our purposes, they are grouped into two sets of two: MACROCYTIC / HYPERCHROMIC large, very red erythrocytes and MICROCYTIC / HYPOCHROMIC small, pale erythrocytes. In the basic CBC test, you will find the MCV (mean corpuscular volume) and the MCHC (mean corpuscular hemoglobin concentration). The MCV gives us information regarding the SIZE of the RBC. The MCHC gives us information regarding the color (or richness of hemoglobin) of the RBC. So, in a patient with a macrocytic/hyperchromic anemia, the MCV and MCHC will be elevated. In a patient with a microcytic/hypochromic anemia, the MCV and MCHC will both be low. The macrocytic/hyperchromic examples we should remember are B12 deficiency anemia (also called pernicious anemia) and Folate deficiency anemia. I realize that some of your references may have categorized the size and/or color of the RBC as somewhat differentbut after these disorders are present for some time in a patient, these size and color features will be present. The microcytic/hypochromic examples include iron deficiency anemia and anemia of chronic disease. B12 deficiency anemia used to be very common before we understood the issues and sources of B12. During the last decade, cases of B12 deficiency are increasing due to the frequency of surgery for Crohns disease (where they might remove the ileum this is where B12 is absorbed) and gastric bypass surgery. Bariatric surgery can lead to B12 deficiency secondary to loss of a protein produced in the stomach called intrinsic factor (IF) which is

44 very helpful in terms of the absorption of B12. Since the stomach is bypassed in this surgery, IF can not be released into the gut and accompany vitamin B12 to the ileum where it absorbed. Patients who have had bariatric surgery will need to take large amounts of B12 orally for the rest of their lives to make sure that deficiency does not occur. Even though they do not have the benefit of IF, they can absorb enough B12 orally to prevent deficiency. Patients who have had their ileum removed due to Crohns disease (or anything else) NEED to have monthly B12 IM injections. B12 deficiency anemia produces the general symptoms of anemia as delineated above, however, if present for more the 7 or 8 years, B12 deficiency leads to irreversible neuropsychiatric issues similar to Alzheimers Disease and schizophrenia. It has been suggested that more then 25% of patients who were kept in insane asylums in the 1800s had B12 def. psychosis. Folate deficiency is best known for the fact that if women are pregnant and folate deficient during the first trimester, there is a much higher risk for the development of neural tube birth defects like spina bifida. For this reason, it is recommended that ALL women of child bearing age take a daily multivitamin with folate as they may become pregnant and be unaware that they are for several weeks after conception. Iron deficiency is relatively rare in developed society as iron is found in protein rich foods. This includes cheap foods like Mcdonalds,etcThe most common etiology of iron deficiency in developed countries is NOT DIETARY DEFICIENCY but menorrhagia (or heavy periods). Even women whose menstrual period flow is on the upper side of normal can become significantly iron deficient. Also, occult GI bleeding like colon cancer and polyps can end up iron deficient. Treatment includes fixing the underlying problem (like giving hormone pills to women to regulate their periods). and then providing supplemental iron. Anemia of chronic disease is extremely common and occurs in those with any chronic disease including COPD/Cancer/ Heart disease, etcMost nursing home residents probably have this to some degree. The degree of anemia seen with this disorder is not as dramatic as with the other anemias. For all intensive purposes, it looks a lot like iron deficiency anemia.but the patients iron stores (reflected in serum Ferritin concentration) are NORMAL. They have iron.they just can not utilize it. This condition is

45 usually not treated unless their hemoglobin level drops enough to cause symptoms. A Few Renal Issues:

Renal hormones

Vitamin D activated through reaction in kidneys Erythropoietin stimulates bone marrow to produce RBC in response to hypoxia
Released from kidneys in response to renal tissue hypoxia Lack of it Anemia of chronic renal failure

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