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RENAL DISEASE AND HYPERTENSION
RENAL DISEASES
I INTRODUCTION TO RENAL DISEASES
Kidneys incredibly complicated & diverse in structure, and function. Variety of diseases impact kidneys including:◦ High BP & kidney disease often related & cause deterioration• Ex. renal artery stenosis contributes to kidney damage DM is one of the main reason for end stage renal failure requiring dialysis Pyelonephritis(usually after bac infection) Glomerulonephritis (post-strep infection, immune complexes build up & damage kidney) Lupus & other autoimmune diseases damage kidneys Anatomical (structural) damage to kidneys▪ Large amount of reserve kidney function—can lose up to 90% function before signs/symptoms develop◦ Very redundant (all parts do the same thing) Not uncommon to have only one & be ok (not a problem to donate) 4 basic morphological components of kidneys: ◦ Vascular & immunologic diseases affect it• convoluted tubules  straight (junctional) tubules ascending and descending tubules of Henle’s loop Susceptible to toxins & BP changes◦ Enough damage & scarring causes kidney failure Renal failure leads to a host of manifestations including the following areas: Blood urea nitrogen (BUN) & creatinine are byproducts of normal metabolism (particularly protein metabolism) Monitor to see if kidneys are functioning Due to salt & water retention and increased renin Renin and angiotensin are two key components of controlling BP Renin/angiotensin system often target of BP meds Biochemical abnormality w/ increased BUN and creatinine (typically due to decreased glomerular filtartion rate—GFR) Prerenal – vascular problems like renal artery stenosis, hypotenstion Postrenal – obstruction of urine flow in ureters or bladder (causes pressure build up) Uremia (clinical term for renal failure)▪ Clinical signs/symptoms along w/ the biochemical changes of azotemia• fluid retention, edema, hypertension, acid/base imbalance, electrolyte imbalance, altered mental state, drowsiness, coma Inflammatory reaction in the glomeruli▪ Majority involve immune system malfunction/immune complexes◦ Ab's against self tissues complex w/ self & clog up glomeruli Group A beta hemolytic strep infection causes it Pt feels abrupt onset of low-grade fever, malaise Clinically shows up as “Nephritic syndrome” (nephritis)▪ An inflammatory condition resulting in:• oliguria (lack of urine flow) and retention of waste products Usually almost no protein loss in normals Low serum protein causes increased production of lipoproteins Caused by degradation in basement membranes of glomeruli increased permeability to proteins  decreased serum protein level lower osmotic pressure  fluid shift into the tissues Low serum protein also  increased production of lipoproteins▪ lipoproteins leak out of damaged basement membranes Diabetes frequently leads to renal disease Many lesions seen in kidneys due to long term effects of diabetes▪ Diabetes  vascular lesions of both large & small vessels▪ Macrovascular lesions – large plaques of cholesterol in arteries• Cholesterol effect magnified in diabetics Microvascular lesions – damage small vessels leading to leakage of endothelium and scaring• Nodular glomerulosclerosclerosis (scaring and thickening of the glomeruli)◦ Leads to proteinuria, and glomerular failure Mesangial sclerosis (diffuse thickening of the mesangium or area around the glomerulus)◦ Clinically: monitor diabetics for proteinuria as one of the first signs of renal disease▪ May not be excessively high but slightly elevated Also control BP more aggressively in DM pts• III. DISEASES OF THE TUBULES AND INTERSTITIUM Inflammation of the tubules and interstitium of kidneys, not primarily in glomeruli▪ Suppurative bacterial infection of kidneys typically spreading from lower urinary tract via bladder & ureters◦ Same pathogens as in bladder infection—E. coli & other GNRs Much more common in females (cystisis spreads up tract)▪ In males, may be because of anatomical predisposition Dilation of ureters due to high progesterone levels Smooth muscle & other tissues relaxes (more dilation of the ureters) Retrograde urine flow more common, bacteria travels up through ureters and into the kidneys Spikes quickly w/ chills, shivers, break out in sweat• Long term & intermittent infection usually related to either obstruction, or reflux disease◦ Reflux occurs as result of ureter not riding along surface of bladder▪ Causes eventual scaring of kidney, and renal failure Not diagnosed until major damage to kidney Tubules susceptible to damage from toxins, inadequate blood flow or infection causing ATN Characterized by destruction of tubular epithelial cells Seen in a variety of clinical settings (severe trauma, pancreatitis, septicemia, etc.) Typically due to a period of inadequate blood flow to the organs from hypotension and shock, or due to nephrotoxic substances (heavy metals, aminoglycosides, etc.)▪ Aminoglycosides are used w/ bad gram (-) rods but can damage kidneys Endotoxins from gram (-) rods cans also cause ATN W/ supportive care including dialysis, very high chance (90-95%) of near complete recovery▪ Ex. pt w/ eclampsia had diffuse intravascular coagulation causing hypotension & ATN Stone formation usually begins in kidneys▪ Solutes crystallize & can cause more crystallization Stones travel down ureters bladder▪ Some narcotics-seekers will put blood in urine sample to get drugs Urethra actually larger & less sensitive then ureters Stones made up of a variety of materials▪ Most commonly calcium oxalate and calcium phosphate (75%)• To prevent more stones recommend increased hydration 15% of stones are made up of magnesium ammonium phosphate (struvite)• Related to chronic urinary tract infections like chronic pylonephritis Must clear stone before infection can be cleared Smaller percentage made of either uric acid or cystine• Due to metabolic abnormalities in excretion of those substances Tx: Usually hydration & pain meds until stone is passed. If situation is severe & blockage causing damage removal or destruction of stone necessary via:▪ lithotripsy- ultrasound waves in bath of water directed at the stone Additionally an “s” shaped stent may be used to connect kidney to bladder to allow urine through Blockage of urine flow leads to dilation of the renal pelvis and calyces, and eventual atrophy of the renal tissues Blockage occurs for many reasons including:▪ Benign prostate hypertrophy is one of the most common causes◦ Painless swelling that cuts of urinary outflow Condition often painless/undetected until damage to kidneys▪ Removing obstruction often allows full return of kidney function if the obstruction hasn’t been there so long as to destroy much of the kidney Symptoms often minimal early on, with blood in the urine (hematuria) being the most common sign▪ Hematuria must be investigated in older pts.
• May be kidney stones, cysts, menstruation (for women), or result of blood thinners (coumadin) Eventually may experience flank pain, weight loss, anemia, etc.
Most common Transitional Cell carcinoma▪ Leads to hematuria which is usually painless Lesions usually superficial & easily treated w/ simple resection (often through a scope), and prognosis very good w/ close follow up• Melanoma can be more serious & needs to be caught early >50 million Americans warranting treatment Worldwide estimates of 1 billion persons affected 3/4 of people >70 years meet criteria for hypertension U.S. Department of Health and Human Services appointed a committee to evaluate impact of hypertension & best approaches to hypertension▪ The Joint National Committee.
Risk for heart attacks and strokes increase significantly w/ increasing blood pressure (both systolic and diastolic)• World Health Organization reports suboptimal BP (>115 mmHg SBP) is responsible for:• #1 attributable risk factor for death throughout the world Normal = Systolic less than 120, and Diastolic less than 80 Pre-hypertension = Systolic 120-139, and/or Diastolic 80-89▪ Used to be “high-normals” but this new name indicates risk Hypertension = Systolic 140+, and/or Diastolic 90+ Stage 1 = Systolic 140-159, and/or Diastolic 90-99 Stage 2 = Systolic 160+, and/or Diastolic 100+▪ Used to be 4 stages but this indicates how deadly the disease is Diabetics – greater than 135 systolic or 85 diastolic = hypertension▪ Tighter regulation because of impact on kidneys Majority of hypertension is Primary or “Essential Hypertension”▪ We don’t know why these people have hypertension (idiopathic hypertension)• Not entirely true, usually secondary to weight/inactivity Smaller percentage have secondary hypertension▪ Hypertension due to another condition such as renal artery stenosis, endocrine tumors, etc.
Usually occurs in younger otherwise healthy individuals Only investigate this if the pt has risk factors for one of the above The evaluation for patients diagnosed with hypertension includes basic screening tests including:▪ looks at electrolytes, blood sugar, kidney, & liver tests looking for proteinuria, hematuria, signs of nephritic or nephrotic syndrome Reveals many of more common causes of 2nd hypertension or congestive heart failure Main objective – reduce cardiovascular and renal morbidity and mortality▪ Primary focus on attaining the SBP goal below 140 • W/ diabetes or renal disease, the BP goal is <130/80 mmHg Over-medication may cause hypotension ▪ when you get up quickly blood has pooled in lower extremities, this creates a decrease of blood to brain until autonomic system kicks in May cause lightheadedness, black-out, fainting More susceptible to orthostatic hypotension when:• Attain and maintain normal body weight (5-20 mmHg) • Depending on how much weight is lost (50-60 lbs would be more significant) Adopt a DASH (Dietary Approaches to Stop Hypertension) eating plan (8-14 mmHg) • Lots of fruits vegetables, and low fat dairy products, and low in saturated and total fats Pt may prefer to die young & impact not that great >30 minutes of aerobic activity most days of the week May be underestimated in Dr. May's opinion◦ May have to cut out alcohol completely because of alcoholism The effect of these depends on if the pt. is near the goal or not For some pts we may have to go straight to step 2• Ex. if severe or pt already doing things in step 1 Used to use a “stepped care” approach to medications• Standard protocol that applied to everyone◦ Now try to individualize medication therapy depending on “compelling indications”• Partly due to variety of different additional affects of the different categories of medications Ex. diabetic pt should start on an ACE inhibitor to help protect kidneys from protein loss & progression of diabetic Ex. pt w/ benign prostate hypertrophy could be put on alpha blockers which will help w/ hypertension & bph If no compelling indicators & they're stage 1 generally start w/ thiazide type diuretic If stage 2 at least a 2 drug combo w/ one of them being a thiazide type diuretic Inexpensive and shown to reduce CV mortality◦ Can cause hypokalemia, especially at higher doses◦ Usually higher doses aren't more effective so not necessary Most other hypertension meds come w/ a diuretic already combined◦ Enhances effectiveness of other meds (synergistically) Shown to reduce risk for second heart attack◦ Standard to prescribe after someone has had a heart attack Sometimes used to treat arrhythmia or tremor◦ So if pt has arrhythmia or tachycardia give them beta blockers great for people w/ situational tremors (ex. proficiency) Can cause marked hypotension with the first dose◦ Recommended first dose at bedtime so they're laying down Help w/ angina/ spasms in coronary arteries Different ones raise or lower heart rate◦ Verapamil constipates people so helpful if pt has chronic diarrhea Used to reduce progression of kidney disease in diabetics
Multiple studies have shown to reduce mortality w/ congestive heart failure, or after a heart attacks
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so w/ diabetes or congestive heart failure think ACE inhibitors Many people can’t tolerate them due to a cough!◦ May be related to blocking angiotensin production which causes precursors to build up in lung tissue leading to irritation & a cough Like ACE inhibitors they reduce the impact of angiotensin, but instead of blocking the production of it, the block the receptors for it and therefore tend not to lead to cough Most of the benefits of ACE inhibitors have been shown with these also◦ Diabetic have slowed renal disease & help w/ congestive heart failure Some insurances will cover if they can't get over the cough Role of the Optometrist in hypertension◦ If measured above 140/90 should be rechecked w/in a year Above 160/100 should be evaluated at PCP w/in a mo If high (240/140) and end organ damage send them to ER Photo documentation of retinal vascular changes THE DIGESTIVE SYSTEM ORAL CAVITY
Apthous Ulcer (AKA Canker sore)
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Lesions are shallow, erythematous, painful ulcers Different ideas: bac, virus, autoimmune, stress Usually based off of what is believed to be the cause• Ex. if bac/viral brush & gargle regularly to clear infection Doesn't stick well unless using Orabase (helps stick in moist oral environment) Herpes Simplex (AKA cold sore or a fever blister)
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By middle-age ~75% of Americans have antibody evidence of infection Antiviral medications topically or orally& supressive meds to prevent• Antivirals work great for pts w/ prodrome◦ Begin using as soon as they notice prodrome Used for ocular herpes infections as well Thrush
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Superficial fungal infection of oral mucosa Appearance: White, adherent, curd-like plaque Often asymptomatic beyond the physical manifestation Common in infants & immunocompromised adults Antibiotics, or corticosteroids may cause it as well• Balance of strep, staph, haemophilis, fungus, etc. offset by antibiotic Paint on topical anti-fungal in infants, may require systemic anti-fungal, or a lozenge. If severe may require IV drugs Leukoplakia and Cancer
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Leukoplakia – Whitish patch on the mucosa caused by epidermal thickening (hyperkeratosis) Part of tissue (unlike thrush) & not inflamed (unlike aphthous ulcer) Associated w/ tobacco use, chronic friction, and alcohol abuse dysplasia – Disorderly, non-neoplastic proliferation of cells considered precancerous
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How often dysplastic tissue transforms to cancer depends on the insult & tissue type Dysplasia is what's looked for in Pap smears or moles 3-25 % transformation to squamous cell carcinoma Survival rates depend on stage at the time of diagnosis 5 year survival ~40% after treatment (surgery, radiation, and chemotherapy) if no recognized lymph node involvement at time of diagnosis• H/e because of rich lymphatic supply metastasis are seen early on W/ evidence of lymph node metastasis at time of diagnosis survival rate at 5 years <20%.
Some believe human pampilloma virus (HPV) may be involved ESOPHAGUS
TERMS –
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Reflux – spill of contents from one are to where they don't belong
For gastro-esophageal reflux disorder (GERD) stomach contents (typically acidic) into esophagus Symptoms usually referred to as heartburn• Symptoms include bitter taste associated w/ a burp Symptoms don't correlate well w/ severity Dysphagia – difficulty swallowing
Minor problem: lack of coordinated peristalsis◦ Major problem: narrowing of esophagus from cancer, strictures, etc Hematemesis – vomiting blood
could be from nosebleed, surgery, or internal bleeding in stomach, etc.
◦ If blood is partially digested in stomach will take on black, coffee ground appearance Hematochezia – rectal bleeding w/ fresh, red blood
Melena – digested blood passed rectally (black and tarry)
Hiatal hernia
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Portion of the stomach works its way into the chest above the diaphragm Negative pressure in this area causes stomach contents to reflux Only small percentage (10%) of affected have symptoms (many asymptomatic) Include heartburn, chest pains, cough and hoarse voice Acid may cause intense esophageal spasm which feel like heart pain◦ Break into sweat, feel nauseous, intense pain, panic attack Symptoms don't correspond well w/ severity Treatment of acid related GI conditions-
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↑ head of bed so gravity helps keep liquids down Cut back on acidic things: tomatoes, citrus, coffee, tobacco, & unique sensitivities Histamine receptors, type 2 found in stomach control acid secretions• Type 1 is the common histamine for allergies Prokinetic agents (metaclopramide, reglan) Enhance normal peristalsis of GI tract• Pushes things forward so they don't reflux sticks to & coats damaged tissue & allows it to heal Quickest, easiest, most effective means to reduce stomach acids available Prilosec now OTC Help most of the symptoms associated with reflux, hiatal hernia, gastritis, ulcers, etc.
Mallory Weiss tear
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Tear in mucosa at gastro-esophageal junction Could be severe if esophageal varices are present Esophageal Varices
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Scarred up liver causes pressure backup in portal venous system Leads to collateral bypass channels and therefore engorged esophageal veins Large veins can rupture, and result in profuse, life threatening bleeding Can be so fragile that tearing is spontaneous Blackmoore tube has 2 balloons at the end which when inflated which anchor it in the stomach & apply pressure to esophagus More common to use endoscope and then apply sclerosing agent or cauterizing the tear Esophagitis and Barrett Esophagus
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Inflammation of the esophagus can occur for many reasons In US most common is reflux of stomach acids (GERD) Could be from direct chemical irritation (drinking battery acid, NSAIDS, doxycycline) pain and a burning sensation in chest right behind heart Severity of symptoms is frequently not correlated with the severity of the inflammation Chronic Esophagitis (2-3 yrs) can lead to Barrett Esophagus Replacement of normal stratified squamous epithelium w/ abnormal metaplastic columnar epithelium• On endoscopy esophagus looks salmon colored & mottled (due to some places being normal & others not) More common in Caucasians than in other races• 30 – 100 fold increased risk of developing adenocarcinoma of the esophagus Usually Barret's has early onset so if they don't have it in 1st couple years not necessary to scope repeatedly• If they do have Barret's should be scoped regularly for esophageal cancer May be treated w/ cauterization (normal squamous tissue grows back) Esophageal cancer
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Worldwide, most cases of esophageal cancer are of the squamous cell variety In US recently adenocarcinoma passed squamous cell carcinoma in frequency Due to increased incidence of Barrett Esophagus• Normal squamous tissue not present in this case so cancer of new tissue Esophageal cancer lower in US than rest of world• Treatment almost always primarily surgical Not very susceptible to chemotherapy/ radiation If spread to lymph nodes prognosis not great If not spread—better but still have problems w/ losing esophagus• Gastritis
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high correlation w/ infection from Helicobacter pylori bac & age◦ 50% of Americans over 50 have H. pylori colonization A gram-negative s-shaped rod that grows well in acid Most people w/ chronic gastritis asymptomatic Significance: predisposition to progress to gastric ulcer or cancer Typically a more severe mucosal inflammation More prone to notice symptoms/signs (b/c of inflammation):◦ W/ H. pylori reduce stomach acid/use antibiotics◦ Ulcers
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Sore in mucosa extending through muscularis mucosa into submucosa or deeper▪ Could be annoying or devastating depending on depth & location May occur along a vessel & cause hemorrhaging (devastating) Strong association w/ infection of H. pylori, but worldwide only about 10 – 20% of people infected with H. pylori develop peptic ulcer Empty areas of stomach inflamed so smaller space=fuller quicker Acid reduction and trying to eradicate H. pylori if found• H. pylori not always easy to get rid of but possible Gastric Cancer
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Strongly associated with chronic gastritis, and infection with H. Pylori Decreasing in incidence in the United States▪ May be improved in countries where they look more for it because caught earlier Due to most people have metastasis already at the time of diagnosis Favored location: lesser curvature of the stomach▪ Ulcer here always deserves endoscopic evaluation—possibly biopsy LARGE AND SMALL INTESTINES
Gastroenteritis
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Term most commonly used to describe a diarrheal/vomiting illness Viral
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Rotavirus, Norwalk virus (common in preschoolers) Bacterial
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ingestion of toxins left from Staph. Aureus (not staph itself)◦ Food poisoning (usually quick onset & lasts 12-24 hrs) infection with toxigenic organism (E. coli, Cholera)◦ infection by enteroinvasive organisms like Salmonella or Shigella◦ antibiotic caused overgrowth of Clostridium dificil and toxin ◦ Protozoa
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Bowel Obstruction
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Normal passage of contents through intestines halted by mechanical obstruction Incarcerated hernia—Intestines pinched & blood supply/stool can't travel through the area Scar tissue (due to surgery or abdominal infections) bowel telescopes into itself and causes blockage bowel twists upon itself and again leads to a blockage Don't put anything in, give IV fluids, suck out gastric juices If not must be removed surgically or there may be ischemia of the bowel and necrosis of the tissues Tumors are another important cause of obstruction If not able to make up lost area colostomy bag may be necessary Appendix (in lower right abdomen)
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Swelling leads to compromised blood flow, and further swelling can lead to rupture Pain that begins in the periumbilical/epigastric area and migrates to the right lower quadrant Increased tenderness (bumps in car are awful)◦ Point where tenderness is felt is called Mc Burney’s point ~2/3 of between the belly button and the ant. sup. Iliac crest Inflammatory Bowel Disease
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Ulcerative Colitis and Crohn’s disease are referred to as Inflammatory Bowel Disease (IBD) Crohn’s disease—granulomatous colitis that may affect any part of the GI tract, but has predilection for terminal ileum & colon
More mechanical complications because more parts affected often develop fistulas (connections between one part of bowel and another) and a lot of adhesions• Avoid surgery because they just grow back Ulcerative Colitis—non-granulomatous colitis that only affects the colon, and leads to an increased risk for developing cancer of the
colon
May be cured w/ surgery if other methods aren't working May be accompanied by fever, joint pains, etc.
Polyps and colon cancer
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Tumorous mass that protrudes into lumen of the gut Can get same thing in flat ‘carpet area’ w/ same sort of pathology Adenomatous polyps – have abnormal epithelial lining • precancerous lesions and should be removed◦ Accounts for about 15% of cancer related deaths in the U.S. Annually Only lung cancer kills more (as far as cancer goes) Lucky if rectal bleeding early on (due to fragility of polyp)• Survival related to spread of disease at time of diagnosis Great survival if caught early & polyps removed Until recently staged using a classification system called Dukes, or Astler-Coller Now usually staged using the more universal TNM staging presence of distant Metastasis (M) of 0 or 1◦ Diagnosis before lymph node involvement makes a tremendous difference in the five year survival rates• Involvement of lymph nodes is the biggest factor in determining prognosis If there are distant metastasis at time of diagnosis prognosis is very poor This is why standard practice is to screen very aggressively for polyps and cancer using an endoscope, and to treat any rectal bleeding in an adult very seriously• Recommended age is 50 or when history of colon cancer present the age the person was diagnosed w/ it (if <50)◦ Old clinical maxim: any anemia in an older male is considered GI cancer until proven otherwise◦ Diverticulosis and Diverticulitis
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Diverticulum – blind pouch leading from lumen of gut By far more common in western societies where there tends to be a refined, low fiber diet• Main significance of this condition is that people w/ diverticolosis can develop acute diverticulitis• Inflammation of one or more of these diverticuli◦ Compromised blood flow, leads to more swelling as the diverticulum, thins out so it can rupture = spill of contents of colon into abdominal cavity and can be devastating If inflamed they can rupture, and be life threatening What causes transition from diverticulosous to diverticulitis is controversial Many believe dietary triggers are common causes of flare-ups Things that come through digestive tract undigested (in solid form) that make their way into these little pouches and lead to irritation as they get stuck in there and fester• tenderness in area of the diverticuli ◦ usually the left lower quadrant near sigmoid colon but can be anywhere in colon Usually antibiotics, liquid diet, & avoid eating things that could lodge in diverticulitis initially IF NOT TOXIC◦ V. LIVER AND BILLARY TRACT
Dysfunction of liver typically leads to stasis of bile ◦ Bile salts build up and leak into blood stream causing jaundice Routinely look at liver enzymes to assess liver status (ALT, AST)
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Liver function is better assessed by serum albumin levels/clotting factors (proteins produced by liver) and the protime test
Jaundice – yellow discoloration of skin and that occurs when systemic levels of bilirubin rise above normal◦ Cholestasis – systemic retention of bilirubin and other solutes (mainly bile salts) that are normally excreted by the liver leads to itching, rashes and variety of other things Cirrhosis
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If liver malfunctions & there has been lots of inflammation leads to scarring or cirrhosis In western countries cirrhosis is among top ten causes of death Anatomically, fibrous bands replace normal liver lobules Fibrosis is seen diffusely throughout the liver• Once fibrosis develops it is irreversible Most common cause is alcoholic liver disease When liver scars 2 different systems of blood flow through the liver: hepatic and venous system.
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When liver scars, the portal venous sys can’t work appropriately and blood flows backward causing dilation of portal veins. Back up influences liver, veins in abdomen, rectum and lower esophagus ◦ When veins around rectum get dilated we call it hemorrhoids
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When they get big and swollen called hemorrhoids See an enlargement of spleensplenomegaly▪ Big dilated veins in esophageal varices due to lack of flow through portal system As bile salts build up you get elevation in ammonia levels (normally cleared in liver) so you can see encephalopy (dementia)▪ One physical sign is a flapping type of tremor
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Holding hand backward causes it to flap in a weird way as an indication of their increased levels of ammonia and other waste products Liver isn’t able to process things, it weeps so you’ll see a build up of fluid in the abdomen and we call this ascities
Hepatitis
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Can be caused by alcohol abuse, other toxic exposures (tylanol od), viral infections, or metabolic conditions Clinically we detect this by jaundice, and elevated liver enzymes Only metabolic condition that causes hepatitis that you need to be aware of is Wilson’s disease• An inherited defect of copper metabolism ◦ Leads to a build up of copper w/ deposits in liver & eye▪ In eye characteristic appearance called Kayser-Fleischer rings iral hepatitis comes in a few different varieties• Vaccines for types A and B, but not for type C Hepatitis A
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Spread by ingestion of contaminated water or foods▪ Shed in the stool of infected individuals Typically a benign, self limited disease, but can occasionally be severe or even life threatening Does not cause chronic hepatitis or have a persistent carrier state.
Hepatitis B
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Acute disease but potential to cause chronic and progressive disease, as well as an asymptomatic carrier state 2/3 of people have subclinical disease Only small percentage that have chronic disease and chronic hep leads to cirrhosis. W/ chronic hep significantly increases risk of hepatocellular carcinoma Hepatitis C
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Recently been identified as a major cause of liver disease Like hepatitis B it is contacted by transfusion, sharing needles or having sexual relations with an infected individual Frequently an asymptomatic initial infection Often a decades long delay between initial infection and clinical disease which shows up as liver failure Hep C is a much more common cause of chronic hep cirrhosis than Hep B Tumors
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Liver and lungs: 2 most common organs involved in metastatic cancer Most common cancers in the liver are metastatic (from colon, lung, and breast most often) Primary liver cancer is uncommon in the U.S., but common is Asian countries due to increased rates of hepatitis B carrier state Hepatitis B carrier state gives a 200 fold increased risk of developing primary liver cancer Hepatitis C also carries an increased risk of leading to hepatic cancer Prognosis w/ primary liver cancer grim—death usually occurs w/in 6 mo of diagnosis A little better if cells rapidly dividing (responds better to chemo) Gall Stones
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Symptoms occur when stone tries to pass through the bile duct pain in the right upper quadrant of the abdomen that is colicky in nature, and radiates to the right shoulder blade• Obstructs flow of bile, and as gall bladder contracts, there’s a lot of crampy (colicy) pain, spasms of the drainage tubes and gall bladder Obstruction from stones is a common cause of pancreatitis Risk factors for cholelithiasis are the five Fs: Meds can reduce occurrence but they tend to come back Can be problem if obstructs common bile duct (leads to panceatitis) Recommended to remove gall bladder & then give steady drip of bile• The Pancreas and the Endocrine SystemIntroduction Substances produced are secreted via ducts• Ex. parotid gland has tubular structure secretes amylase for digestion to mouth Ex. csytic duct, hepatic duct, and pancreas all drain into common bile duct where digestive juices and end products of metabolism go into intestinal system Substances produced are secreted into the surrounding tissue• Autocrine – substance acts on the cell that secretes it Paracrine – substance affects cells in the immediate vicinity of the cell that released it Endocrine – substance released into the blood stream acts on target cells at a distance Secreted molecules in the endocrine system frequently called hormones Hormone classification based on nature of receptors (2 types)◦ Either interacts with cell-surface receptors▪ Peptide hormones – growth hormone, insulin Originally thyroid gland (controls metabolism) was thought to be central gland but then pituitary was found to control thyroid & others Bean shaped structure lies at base of the brain in sella turcica ◦ Enclosure can cause problems if pituitary expands (mass effect)▪ Hypothalamus (sup to pituitary) connects to pituitary via “stalk”◦ Hypothalamus secretes substances down stalk influencing ant or post pituitary gland Most problems don't occur in hypothalamus but the pituitary Central role of regulating most endocrine glands Composed of two functionally distinct components:◦ Anterior pituitary – releases trophic hormones▪ Hypothalamus secretes substances to cause ant pituitary to release hormones Posterior pituitary – axons from nerve cell bodies in hypothalamus extend here▪ Causes uterus to contract down to reduce bleeding after pregnancy Synthetic oxytocin (pitosin) given in delivery room Symptoms of disease due to problem with the gland:◦ Excessive secretion of trophic hormones• Usually manifests as a change in gland regulated by trophic hormone Usually due to anterior pituitary adenoma (tumor of gland—not cancer)• 1/4 of population though many assymptomatic Sheehan syndrome occurs postpartum—mother becomes hypotensive from blood loss which reduces blood flow causing ischemic necrosis to part of pituitary Surgery or radiation that destroys part of pituitary Doesn't secrete anything but hinders function Ex.of hypopituitarianism:Ant stops producing TSH & thryoid stops working causing hypothyroidism◦ When we see this we must discover if due to gladular issue, pituitary issue, or both May compress decussating fibers of the optic chiasm• Rarely due to excess or lack of hypothalamic factors Overactive pituitary secreting too much trophic hormone Most common cause: Pituitary adenoma (anterior lobe) ◦ Can be functional (produces hormone) or silent (not producing enough to manifest Amenorrhea, galactorrhea (discharge from breast), infertility, reduced sex drive Check blood count, chemistry panel, thyroid, prolactin level Gigantism occurs when epiphyseal plate hasn't sealed so bone grow long Acromegally occurs after epiphyseal plate has seadled so only hands, feet & jaw grow disproportionately▪ Problems w/ ACTH which affects adrenal gland All may lead to hypopituitarism via mass effect▪ If pituitary gets too big may damage or effect different areas than just the one w/ the tumor Posterior Pituitary Syndrome (only 2 hormones): Abnormal stimulation is not related to significant clinical abnormalities▪ Causes kidney to retain water (stop urination) Underproduction – diabetes insipidus▪ Overproduction - syndrome of inappropriate ADH secretion (SIADH)▪ Can be caused by small cell carcinoma of lung which produces this type of hormone Ischemic necrosis of the anterior pituitary Clinical features depend on which hormones are lacking Location: at base of neck between meeting of 2 sternocleidomastoid muscles◦ When enlarged creates goiter (seen in many old paintings) Up-regulation of carbohydrate/lipid catabolism▪ Therefore, increase in basal metabolic rate Hypothalamus releases thyrotropin releasing hormone (TRH) which causes ant pituitary to release TSH (thyrotropin) which stimulates the thyroid gland to release T4 (thyroxine—4 idodines) and T3 (triiodothyronine—3 iodines)◦ Control of thyroid via (-) feedback system▪ Too much T4/T3 at ant pituitary/ hypothalamus decreases production Can't shut down adenoma from producing too much or a thyroid adenoma (prodcuing T3/T4 uncontrolled) Excessive release of preformed thyroid hormone due to:▪ Pituitary gland problem (pituitary adenoma) Autoimmune stimulation of thyroid gland • Grave’s disease causes overstimulation of thyroid Thyroid derived from undersurface of mouth embriolocially• Occasionally tissue continues under tongue & down throat Heat intolerance, weight loss, warm skin▪ Cardiac – palpitations, tachycardia (>100 BPM) Neuromuscular – nervousness, tremor, antsy Ocular – wide, staring gaze, lid lag▪ Due to upper lid muscle overstimulation (says he.) Tests both hyperthyroidism & hypothyroidism Decreased production of thyroid hormone◦ Primary (problem w/ gland itself) – problem with thyroid Secondary (problem outside of gland) – hypothalamic/pituitary disease Himalayan mountains regions, Africa, China Pituitary continues to demand more production & thyroid becomes hyperplastic & grows to try & make more but can't TSH most sensitive screening test for this disorder Most common thyroiditis in areas where iodine levels are sufficient Because as Ab's destroy follicles in thyroid they release their contents May take 6 weeks to notice equilibrium◦ Must be careful not to cause hyperthyroidism—tachycardia, palpitations Infiltrative ophthalmopathy – exophthalmos▪ post. massive infiltrate of mononuclear cells Puts pressure behind eye and starts to push eye out Scaly thickening and induration of skin on lower aspect of leg Orange-peel texture due to skin pushing out under pressure Can cause exposure keratitis and conjunctivitis due to dry eye Due to impaired synthesis of thyroid hormone◦ Airway obstruction or cough (pushing on trachea) Suppressive therapy w/ thyroid hormone so the thyroid can be taken out of the picture Location: close to the upper and lower pole of each thyroid lobe Activity of gland controlled by free calcium in the blood not by the hypothalamus or pituitary gland Increases conversion of vitamin D to active form▪ Helps absorb calcium from the intestinal tract Phosphate & calcium counterbalance each other Autonomous, spontaneous overproduction of PTH Depression, psychosis, mental disturbances Nonparathyroid diseases and malignancy◦ Cancer causing high Ca in blood which shutsdown PTH Caused by chronic depression of serum calcium levels Most common cause – chronic renal failure▪ Decreased phosphate excretion -> depresses calcium levels ->elevated PTH Accidentally remove parathyroid w/ thyroid Secretes insulin, glucagon, somatostatin• A clearing factor: clears sugar from bloodstream Beta cells of the Islets of Langerhans • Secrete enzymatically inert proenzymes from pancreas to intestines• Trypsinogen inside intestinal tract cleaved into trypsin causes proenzyme activation Pancreas secretes bicarbonate , anti-trypsin & mucous to protect the duct◦ Enzymes activated by low pH (acid) so bicarbonate keeps it neutral Amylase and lipase are exceptions (go in live forms) Reversible if cause of inflammation removed Alcoholism, hyperlipoproteinemia (triglycerides should be <150) Pancreatic ducts dump into the duodenum via sphincter of Odii If there’s a problem with sphincter (gall stone blocks sphincter) it backs everything up inside pancreas some enzymes activated and cause acute inflammation in pancreas Amylase also made in parotid/salivary glands Irreversible impairment of pancreatic function Can be caused by repeated episodes of acute pancreatitis Lose both exocrine (digestive) and endocrine (glucagon/insulin) function Opiates cause sphincter of Odi to constrict When sphincter closes that also blocks the liver which produces bilirubin A group of metabolic disorders with a shared feature – hyperglycemia Due to defects in insulin secretion, insulin action, or both In the U.S. affects 21 million people (7% of the population) Non-traumatic lower extremity amputation▪ cut a toenail, gets infected, can’t resolve infection, and end up w/ amputation Increases risk of coronary artery disease and cerebrovascular disease Desired blood glucose level 65-99 (fasting or not) Glucose level from 100 – 125 mg/dl – impaired glucose tolerance NOT prediabetes◦ Increased risk of cardiovascular disease▪ Blood sugar too high can damage blood vessel endothelium, causing plaque to build up, leading to obstruction and damage to organ to which that blood vessel feeds Fasting glucose level of >or= 126mg/dl▪ Random glucose level of >or= 200mg/dl▪ Glucose level >or= 200mg/dl 2 hours after a standard carbohydrate load (75 gm of glucose) Glucose binds irreversibly to the RBC Hgb (called HgbA1C) RBC’s last 120 days with an average of about 60 days.
Measures average glucose level over the past 2-3 months▪ Checks compliance with medications, diet, and exercise Perform q3mo for insulin treated patients Perform q6mo for non-insulin treated patients Fasting glucose evaluates the glucose level at that moment Fructosamine (Glycated Serum Protein GSP )◦ Useful when HgbA1C cannot be used (due to hemoglobin problem) Measures average blood glucose for past 2-3 weeks Absolute deficiency of insulin secretion• Autoimmune attack causing Beta-cell destruction• takes a while for insulin to drop as cells are destoyed Combination of peripheral resistance to insulin action and inadequate insulin secretion• Metformin increase cell receptors’ sensitivity to insulin—makes it more conducive to reacting w/ insulin Normal glucose homeostasis is regulated by◦ Breakdown of glycogen stores via glucagon Actions of insulin and counter-regulatory hormones (glucagon) Increases glucose transport into cells▪ Affects striated and cardiac muscle cells and adipocytes Other sites, especially the brain, are independent of insulin Reduces production of glucose from the liver Binds to receptor site of cell which triggers intracellular response Glucose stimulates its synthesis and release Onset is abrupt though chronic attack on beta cells occurs for years before symptoms▪ Millions of beta cells take a while to destroy ketone bodies formed b/c can’t get sugar into our cells so metabolize other substances (If metabolizing fat ultimately breaks down into ketones) Overt diabetes occurs with increase insulin need – infection Blood sugar > 180 mg/dL sugar spills in urine & osmotic pressure pulls fluid w/ it Body needs to drink more because peeing more Body recognizes it's starving because of breakdown of fats, etc Ketone bodies form from fat breakdown & cause acidic state Type II – Non-insulin dependent diabetes◦ First-degree relatives including fraternal twins – 20-40% Decreased tissue response to insulin (insulin resistance)• tends to happen in individuals that are in nursing homes, that have had a stroke, that are not able to sense that they want Hyperosmolarity of blood b/c spill sugar in urine drawing fluid out & don’t realize that thirst factor so they start to dehydrate which develops into a hyperosmolar state Will affect the brain since it is so sensitive to pressure/osmolarity Concerned that if doing that, they’ve lost any sense of insulin secretion or response to insulin & hedging over towards type I diabetes. Diagnosis made after routine blood or urine testing or unexplained weakness or weight loss Glucose metabolized to sorbitol -> fructose• Fructose doesn't diffuse easily across cell membrane Leads to intracellular edema -> cellular dysfunction -> cellular death Not enough insulin so sugar can't enter muscle, fat, or liver High blood sugar spills out through kidney and urinate more Eat more since fats and proteins being broken down (hunger reflex) Lose weight because not metabolizing substances being taken in Unless blood sugar very elevated you can live w/ diabetes a long time Renal vascular insufficiency (kidney malfunction) Lazer treatments coagulating the area hoping to stop potential bleeding from hemorrhages Bed-ridden pts can't feel pain & move leads to ulceration Trouble if clip nails—can get infection w/o knowing & lose foot◦ Requires salami procedure—amputate until reach an area w/ enough blood supply to heal Women with Gestational DM are at greater risk for DM later in life Focus on eyes, heart, vascular system and neurological system SMAC: chemical panel for liver enzymes, electrolytes, and proteins Chest X-Ray: size of the heart—is it enlarged or is anything else going on there? Abnormal glucose levels as previously indicated Oral medications that stimulate insulin release Oral medications that affect insulin receptors Paired endocrine glands located on the superior pole of the kidney◦ Not interconnected w/ kidney—unique blood supply 3 layers (each one secretes a different hormone Aldosterone result of renin changing angiotensinogen to angiotensin I which causes angiotensin II which causes secretion of aldosterone Excess cortisol due to oversecretion of ACTH from ant pitiuitary• In clinical practice, usually iatrogenic• Centripetal swelling of tissue (going in) head & face coming into body Can mimic DM – gluconeogenesis and inhibits glucose uptake by cells Primary – aldosterone-producing adrenocortical neoplasm or primary adrenocortical hyperplasia (problem w/ gland itself) Secondary – response to activation of the renin-angiotensin system• Kidney senses pressure drop & secretes renin.,etc◦ Treat these (primary & secondary issues & problem solved) Sodium retention and potassium excretion• Increase sodium, increase fluid, increase volume within blood vessels  hypertension Due to progressive destruction of the adrenal cortex▪ Anorexia, nausea, vomiting, diarrhea, weight loss Any stress that taxes their limited physiologic reserves If on steroids for 3 mo, can't suddenly stop b/c shutdown adrenal glands Primary chronic – Addison’s disease◦ Progressive destruction of the adrenal cortex Disorder of the hypothalamus and pituitary gland Put them on different medications to prevent the blood pressure from going up

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