urethral obstruction (eg, prostate hyperplasia& hypertrophy in men, BPH benign prostatic hyperplasia), spastic bladder, flaccid bladder

cells multiplying, pressure on sac pushes on urethra and prostate, causing them to contract more.

spinal cord injury (at or above the level of S2) strokes (brain attacks) (bladder disorders persist longer than one year in about15% of stroke patients), traumatic brain injury, multiple sclerosis (bladderdisorders are reported in 40-90% of individuals with MS)

bladder distention, hesitancy, straining, small and weak stream, frequency, feeling of incomplete bladder emptying; increased frequency of attempting to urinate.

straight, collapsible tube made of smooth muscles(about 25cm) that lies behind the trachea and functions primarily as the passage of food from the pharynx to the stomach.  It opens into the stomach through the cardiac orifice.

forms the middle portion of the digestion tract consists of the duodenum (22 cm/10in long, connects the stomach to the jejunum and contains the opening for the common bile duct and the main pancreatic duct, bile and pancreatic juices enter through these ducts) and the jejunum and ileum (together are 7 m/23 ft and are folded onto themselves to fit into the cavity, here food is digested and absorbed)

(mucosal & parietal cells) – essential for B12 absorption, helps RBCs mature by transcribing DNA correctly.

(HCl; pH 1.0 mucosal and parietal cells)

gastric analysis - effect of histamine (* increases gastric acid secretion) histamine attaches to same receptor sites as gastrin. Triggers hypersecretion of gastrin

loss of appetite can be due to loss of smell, emotional factors, drugs, and disease.  Often a forerunner of nausea, and most conditions that cause nausea and vomiting also produce anorexia

- ill -defined and unpleasant subjective sensation of stimulation of the medullary vomiting center that often precedes or accompanies vomiting, and stimuli (food and drugs) that cause anorexia is small doses usually produce nausea in large doses.  A common cause is distention of the duodenum of upper small intestinal tract.  Frequently accompanied by autonomic nervous system manifestations such as watery salivation and vasoconstriction with pallor, sweating, and tachycardia.  May function as an early warning signal of a pathological process

forceful expulsion of food and fluid; protective mechanism; effect of hypoxemia on vomiting center.  The chemoreceptor trigger zone is located in a small area of the floor of the fourth ventricle, where it is exposed to both blood and cerebrospinal fluid.  It is thought to mediate the emetic effects of blood-borne drugs and toxins.  The act of vomiting consists of taking a deep breath, closing the airways, and producing a strong, forceful contraction of the diaphragm and abdominal muscles along with relaxation of the gastroesophageal sphincter.  Respiration ceases.  May be accompanied with dizziness, lightheadedness, a decrease in blood pressure, and bradycardia.

Hematemesis

Melena

Dysphagia

Esophageal Diverticulum

Tears (Mallory-Weiss Syndrome)

Achalasia

Gastroesophageal reflux

Hiatal hernia

Oropharyngeal Cancer 

difficulty in swallowing or perception of difficulty swallowing ,  typically from cancer or scarring of esophagus

 Longitudinal tears in the esophagus at the esophagogastric junction, most common in people with chronic alcoholism after a bout of severe vomiting/retching, but may also occur during acute illness w/ severe vomiting.  Inadequate relaxation of the esophageal sphincter during vomiting, with stretching and tearing of the esophageal junction at the moment of propulsive expulsion of gastric contents.  Infection may lead to inflammatory ulcer or mediastinitis.

(accounts for about 40% of GERD), Type 1 and Type 2 – could happen from wretching. thoracic cavity and abdominal cavity is separated by the diaphgram and a hole.

Hernia when tissue moves from where it should be to where it shouldn’t be. Stomach antrum fundus, lower tntrum sphincter. Type 1 medically managed, type two must be surgically fixed =l

                      1.     Partial herniation of stomach through diaphragm into thorax

                      2.     Conditions predisposing toward herniation -

                              a.     Congenital or acquired weakness of hiatal muscle

                              b.     Increased intrabdominal weakness of hiatal muscle

                              c.     Congenital or acquired shortening of esophagus 

hole was took big -  = frat boys “ where the party at?totlling hiatal hernia less tight.  Balloon of food form bubbles. Lots of pressure on the food in bubbles tumor outside HCl would get out and leak all over wall and heart and esophagus. Surgery is very invasive.

                                              3.     S and SX are similar to gastroesophageal reflux:  Pain, heartburn after meals                

                                                      (at-night pain that may be confused with angina), sour taste in mouth

1.           increasingly considered an STD also caused by tobacco & alcohol

                      2.     evidence of prior oral HPV infection -16. = a 32-fold increased risk of mouth/throat CA.;

                              risk is almost nine times higher for people who reported oral sex with more than six

                              partners; HPV-16 accounts for 72% of all cases in those ≤ 50; prognosis mixed….

oral HPV seen in 10% of men and 4% of women in US {26jan2012, JAMA}, HPV-16 in 1%: now recommend the use of barrier protection during oral sex & ‘deep kissing’

watery, non-bloody diarrhea & abdominal

cramping, fever. (note: rotavirus’ #1 cause of severe diarrhea in children world wide, fecal-oral transmission, infections/spread peak in winter, GOOD HANDWASHING). Benign and self limiting. Most bacteria don’t have adhesion molecules. They increase bowel motility and adults mostly bacterial, kids mostly viral

1.                     Peptic ulcer - term used to describe upper GI tract ulcerative disorders

                                              2.     Most common - duodenum (duodenal ulcers) and stomach (gastric ulcers)

                                              3.     Predisposing factors

                         c.   presence of Helicobacter pylori (H.pylori) is the leading cause (80-90%) most are antral.

1.           common in gastric fundus (remember effect of histamine upon parietal cells?)much lower pH, histamine attaches to receptor sites of

                                              2.     risk factors: major histamine release, massive trauma, severe burns, sepsis, liver failure, major surgery, NPO  

                                              3.     may result from ischemia, tissue acidosis, and bile salts etc.

                                              4.     manifestation: epigastric pain & upper-GI tract bleeding (large volume)

1.           Common in 50-70 age group

                                              2.     Risk factors - genetic predisposition, carcinogenic factors in diet (smoked food, nitrites, HCAs), atrophic gastritis, gastric polyps, etc.

                                              3.     Common site: antral region & adjacent to pyloris (ie, related to H.pylori)

                                              4.     Usually asymptomatic or vague indigestion symptoms 

a functional gastrointestinal disorder characterized by a variable combination of chronic & recurrent intestinal symptoms not explained by                                       structural or biochemical abnormalities”

hyperactive, generally lower (small) intestine. Regional is more than one spot, become lactose intolerant because it dairy products trigger inflammation, this causes protein deficiency

                                              1.     recurrent inflammatory response, slowly progressive, relentless, and often disabling disease - related to hyperactivity in immune system -- (HLA-II proteins are used on the surface of WBCs so they can identify each other, alterations in these proteins are associated with DR1 risk- ineffective way of communicating, cells get confused and send the wrong messages)

                                              2.     all layers involved (transmural), eventually becomes thickened and inflexible. Most common site: ileum; onset 15-25 years of age, women more than men

                                              3.     clinical manifestations - intermittent diarrhea, severe colicky pain, weight loss, malaise, low-grade fever, bleeding, malabsorption, mild leukocytosis.

                                              4.     complications - intestinal obstruction, abdominal and perianal abscess formation, fistula (rectocutaneous, etc.) formation, arthritis/arthralgias, iritis, aphthous ulcers(oral “canker sores”), cholelithiasis, lactose intolerance, etc. 

a lot less bleeding than Crohn's, happens in the descending colon- typically in the sigmoid colon, 3 or more lesions from the mouth to the anus, lower left quadrant cramping and diarrhea

                                              1.     nonspecific inflammatory condition of colon/rectum

                                              2.     usually submucosal-mucosal layers only, necrotic, ulcerate, small amount bleeding, diarrhea,

                                                      fever, acute abdominal pain, anorexia, weakness, abdominal cramping

1.         complications - cancer, toxic megacolon, others similar to regional enteritis

1.      Active/severe phase- ulcers are bright red, massive amounts of diarrhea (3 or more diarrhea stools a day with severe abdominal cramping and spontaneous expulsion full of digestive enzymes) 20% mortality in the first two years due to hypovolemia and shock

2.      Moderately active phase- symptoms are less severe, but still a lot of diarrhea

diverticulosis- the condition of having at least one diverticula, ~1% of the population, vs. diverticulitis- inflammation typically in the sigmoid colon)

                                              1.     A diverticula is defined as a ‘herniation of mucosal layer occurs through muscularis layer’

                                              2.     most common site:  Sigmoid colon

                                              3.     risk factors - diet (lack of insoluble fiber; too many processed foods which make us suck water out of the gut), decreased physical activity, poor bowel habits (ignoring the urge to defecate, and, not squatting to defecate, effects of aging that slow bowel

4.     ill-defined left lower abdominal discomfort, diarrhea, constipation, bloating, flatulence, maybe severe pain with fever & bleeding

Noninflammatory diarrhea, watery and nonbloody stools, cramps, bloaring, nausea, or vomiting.  Commonly caused by toxin producing bacteria (E. coli, S. aureus, Vibrio cholerae) or viruses that disrupt the normal absorption or secretory process in the small bowel.  Prominent vomiting suggests viral enteritis or S. aureus food poisoning.  Although typically mild, the diarrhea (which originates in the small intestine) can be voluminous and result in dehydration with hypokalemia and metabolic acidosis (cholera).  Because tissue invasion does not occur, leukocytes are present in the feces

Inflammatory diarrhea is usually characterized by the presence of fever and blood diarrhea (dysentery).  It is caused by invasion of intestinal cells (Shigella, Salmonella, Yersinia, and Campylobacter) or the toxins associated with the previously described C. difficile or E. coli infection.  Because infections associated with these organisms predominantly affect the colon, the diarrhea is small in volume (<1L/day) and is associated with left lower quadrant cramps, urgency, and tenesmus.  Infectious dysentery must be distinguished from acute ulcerative colitis, which may present with bloody diarrhea, fever, and abdominal pain.  Diarrhea that persist for 14 days is not attributable to bacterial pathogens, and the person should be evaluated for chronic diarrhea

Persons with this usually have symptoms directly referable to the gastrointestinal tract that include diarrhea, steatorrhea, flatulence, bloating, abdominal pain, cramps, weakness, muscle wasting, weight loss, and abdominal distention.  Wight loss often occurs despite normal or excessive caloric intake. 

            Steatorrhatic stools contain excess fat.  Along with loss of fat in the stools, there is failure to absorb the fat-soluble vitamins.  This can lead to easy bruising and bleeding (Vitamin K deficiency), bone pain, a predisposition to the development of fractures and tetany (Vitamin D and Calcium deficiency), anemia and glossitis (folic acid deficiency).  Neuropathy, atrophy of the skins, and peripheral edema may be present

                                      1.     impaired absorptive function – especially noticeable malabsorption of vitamins & minerals

                                      2.     causes are multiple - includes small bowel disorders (Celiac Disease& Non-celiac gluten intolerance [NCGI] – which affect 1:100 and 1:10 Americans respectively)

                                    3.     manifestations are dependent upon cause.  Commonly diarrhea with alternating

                                            constipation, dehydration, weight loss, steatorrhea and abdominal discomfort

                                      4.     failure of absorption with vitamins A, B12, D, E & K cause manifestations              

                                              specific to lack of each (e.g. K lacking = easy bruising and bleeding)

3rd most common site & 2nd most fatal cancer in both women and men in the U.S.** precursor is usually the presence of adenomatous polyps- precancerous polyps in the colon (by age 45-50, about 20% of the U.S. population has one or more adenomatous polyps [an adenoma is a benign but often pre-cancerous tumor originating from epithelial tissue])

familial adenomatous polyposis (FAP) & hereditary non-polyposis colorectal cancer (NHPCC) together account for about 5% of cases, family history of cancer, ulcerative colitis, low-fiber & high-fat diet, cigarette smoking, over age 50; AND beef & heterocyclic amines (HCAs) [see syllabus p.56]; seventeen different HCAs have been identified that are carcinogenic in humans.

i.                      muscle meats cooked at temperatures above about 325o F

             ii.   flame-grilled, broiled, or pan-fried meats

    iii.  muscle meats cooked for long periods of time (ie, barbeque)

 iv.        meats -- beef #1, then pork, poultry, fish

early symptom:  bleeding into stool other symptoms = change in bowel habits, pain is a late symptom

Largest organ
Dual blood supply – 400cc hepatic artery, 1200cc portal veins to ____ 

(at 4 mmHg pressure);  and then hepatic vein to IVC from ____.

excessive destruction (hemolysis) of RBC's (major cause), decreased uptake of bilirubin by liver, decreased conjugation of bilirubin by liver, obstruction of bile flow (gall stones) out of liver

Inflammation of the liver due to reaction to drug and/or toxins; from infections such as malaria or from virus

blood borne infection, carrier state moreserious (about 50% of acute infections become chronic), 1% result in ‘fulminant’ form; vaccine available (HBV has smallest genome of any human DNA virus) ‘serum hepatitis-passed through the blood’, non-lytic (not killing the host cell, body activates T cells) & enveloped virus (become chronic), incubation period 60-170/d

Liver collapses on itself, will lose hundreds of thousands of hepatocytes, collapsing plates on blood vessels that have low pressure, causes cirrhosis (liver failure), changes shape/anatomy, portal hypertension

similar to B, usually less serious acutely but more may become carriers (ie, chronic infections in ≥80%; cirrhosis ≥13%)‘serum hepatitis-passed through the blood’, non-lytic & enveloped virus, incubation period 60-170/d

Liver collapses on itself, will lose hundreds of thousands of hepatocytes, collapsing plates on blood vessels that have low pressure, causes cirrhosis (liver failure), changes shape/anatomy, portal hypertension

may follow hepatitis B & C in Arizona, 40% of all liver failure is from chronic Hep. C infections, HCV is “the most common chronic [active] blood borne infection in the U.S.”

caused by alcohol ETOH (ethanol; grain alcohol) abuse

                                    Distilled alcohol has no carbohydrates, only alcohol sugars (when metabolized in the liver, don’t turn into glucose, only turn into cholesterol-triglycerides).  So drinking any hard alcohol will turn into fat in the liver and the hepatocytes will be damaged and will accumulate alcohol and fat because they are trying to turn the alcohol sugar (sorbitol) into fat.  Hepatocytes require more energy when they are filled with sorbitol Hepatocytes will then swell and fill up with water and the membrane will start to tear and eventually rupture.  The more you drink, the more hepatocytes will be killed, which will further impair the loss of the liver, and lead to cirrhosis…(as opposed to drinking beer/wine which partially turns into glucose, and increases HDL).  Glucose is a tiny crystalline structure that can sometimes cut/damage other cells and proteins.  Sorbitol is a HUGE crystalline structure that always bumps into other cells and damages them.

25% of alcoholics develop cirrhosis

vague at first, fatigability, weight loss, abdominal pain in URQ,

                                                              diarrhea or constipation, palpable liver, easy bruising (failure of liver to               

                                                              make clotting proteins), nausea & vomiting, esophageal varices (GI                    

                                                              bleeding), external hemorrhoids (varicosities at the level of the lower                  

                                    rectum or anus), ascites (a function of portal hypertension and liver failure, intraperitoneal edema-when fluid gets into the peritoneal space, there is no way to get the fluid back, so it fills the peritoneal space and it will never be recovered by the client, so much water can accumulate that you look pregnant), jaundice (secondary to bilirubin [unconjugated or conjugated tells if it’s a gall bladder or liver problem]), pruritus (itching, but not due to the skin, tells you that something is wrong with toxins building up), hepatic encephalopathy-something wrong with the nervous system due to the liver(secondary to ammonia-extremely poisonous, ammonia test both hands start flapping),  hepatorenal dysfunction –kidneys are failing because the liver failed (multiorgan system dysfunction), gynecomastia (increased testosterone), amenorrhea (due to increased testosterone, and loss of estrogen)

surgery, chemotherapy, 5-fluorouracil (5 FU), methotrexate

regularly secretes 800cc’s of bile which is full of bile salts which helps with the emulsification of fats, also in the bile is junk (including cholesterol) which is transferred to the stool.

cells that make and secrete chemicals that are dumped into the duodenum

both endocrine and exocrine organ

                                      pancreatic enzymes secreted in in/active forms - proteolytic enzymes like amylase, lipase, so pancrease does not (normally) digest itself

            large functional reserve:  symptoms occur late  

big relationship to morbidity/mortality in many diseases (central obesity- a waist circumference of >30 in women, and >40 in men, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, hypertension, hyperglycemia [if you meet 2 of the 5 criteria for metabolic syndrome, you are 4 times more likely to die of a fatal heart attack or stroke, 3 criteria=9x more likely, 4 criteria=14x more likely, therefore there is an interactive effect, creates an exponentially greater risk when presented together] with/without insulin resistance)

  34% of US residents ≥20 years of age

          exceed three or more of the Metabolic Syndrome criteria

test used: total protein/serum-albumin level…deficiencies # 1 complication/cofactor, huge correlation between this level and their survival rate "A systematic review of cohort studies (1997) estimated that for each 2.5 g/l

                              decrement decrease in serum albumin concentration the risk of death increases by

                                    between 24% and 56%."

Cortisol, controlled by ACTH secretion, effect on:

glucose & protein & fat metabolism

anti-inflammatory action

psychic effect

‘permissive effect’ 

female fetus masculinized

autosomal recessive, where androgen precursors are not converted into cortisol/aldosterone

 increased levels of ACTH lead to adrenal hyperplasia & increased androgens

                    ranges from simple virilizing CAH to complete salt-losing enzyme deficiency

 (low Na; which is seen with deficiency of 21-hydroxylase enzyme only; converts 17-OHP) 

 a relatively rare disorder in which all the layers of the adrenal cortex are destroyed.  Autoimmune destruction is the most common cause in the US.  Rare causes include metastatic carcinoma, fungal infection, cytomegalovirus infection, amyloid disease, and hemochromatosis.  Bilateral adrenal hemorrhage may occur in persons taking anticoagulants, during open heart surgery, and during birth or major trauma.  Adrenal infufficiency can be caused by acquired immunodeficiency syndrome, in which the adrenal gland is destroyed by a variety of opportunistic infectious agents.  Drugs that inhibit synthesis of cause excessive breakdown of glucocorticoids can also result in adrenal insuffiency.  Addison’s is a chronic metabolic disorder that requires lifetime hormone replacement therapy.  The adrenal cortex has a large reserve capacity, and the manifestations of adrenal insufficiency usually do not become apparent until approximately 90% of the gland has been destroyed.

chronic metabolic disorder - requires lifetime hormone replacement therapy 

life threatening [‘salt, sugar, steroid’ replacement]

lifetime replacement glucocorticoid therapy;
IV glucose and saline acutely

Diabetes (means to pass through quickly) Mellitus (to taste like honey)
THE SEVENTH LEADING CAUSE OF DEATH IN THE UNITED STATES IN 2009
disorder of carbohydrate, fat, and protein metabolism resulting from an imbalance between insulin availability and insulin need.  Ranges from absolute deficiency or the insulin produced is not active or is destroyed too soon, etc.

11.3% of U.S. residents age 20 or above had diabetes (diagnosed + undiagnosed) at the end of 2010 “X factor” -- 35% of U.S. residents age 20 or above were “pre-diabetic”, based on fasting glucose and/or hemoglobin A1C levels, at the end of 2008 

“The American Diabetes Association has noted, from the 2003 assessment of the National Center for Chronic Disease

Prevention and Health Promotion (Centers for Disease Control and Prevention), that [‘at current increasing incidence rates’]

1 in 3 Americans born after 2000 will develop diabetes in their lifetime.” 

{insulin production of 0.6 units per Kg per day = need 42 units/day in a healthy 70 kilo adult}

                      HLA-II : DR, DP, DQ : 1, 2, 3, ……….

make and secrete a chemical called somatostatin, which blocks the action of insulin and glucagon and the hyperglycemic effects of epinephrine, caffeine, and nicotine

blood sugar less than 50 mg/decaliter of blood (normal is between 70 and 90, but if its below 50 not enough neurons are getting to the brain, not efficient enough, lack of ATP, level of consciousness begins to deteriorate, neurons in the brain do not store in glucose in the brain which means if there isn’t enough in the bloodstream then they are completely out) (typically happens when there are other physiological problems)
When the blood sugar falls below 40, the person loses consciousness
When the blood sugar falls below 30, the neurons die

Any unconscious patient that we assume of being diabetic probably has this (give them sugar) 

Onset and rapid progression (vs slow onset hypoglycemia generally) 

Autonomic nervous system responses (e.g. sweating, skin pale & cool, anxiety, confusion, tingling in the lips) in addition to other endogenous efforts to restore blood glucose 

William Osler. (1892). Principles and Practice of Medicine. New York: D.Appleton and Company.

1:100,000 and 1-2 cases of type 2 per 100,000

2 to 3 cases of diabetes per 100,000 population in Europe and North America

at the end of 2010, 11,300 cases of diabetes per 100,000 population ≥20 years of age in the USA

The American Diabetes Association,

“at current increasing incidence rates,”

33,333 per 100,000 Americans born after 2000 will develop diabetes in their lifetime

1 out of every 3 could be a type 2 diabetic

Polyol pathway (glucose -->  sorbitol -->  fructose)

Formation of abnormal glycoproteins producing structural defect in basement membrane
 

Problems with tissue oxygenation (accelerated atheroma formation)

Nephropathies (mircovascular)

rapidly progression chronic arterial disease

risk factor with type 1 - both age and duration of diabetes correlate
Foot ulcers - effects of both neuropathy and vascular insufficiency (Most common cause of non-traumatic limb amputations in U.S. (the limb was dead so it must be amputated) 

Stub their toe and get injured but they don’t know they got injured, so it happens again, and gets worse and worse, spreads, and can eventually call off
Have been reported as the most common complication leading to hospitalization for people with diabetes, it represents the effect of neuropathy and vascular insufficiency.  Distal symmetric neuropathy is a major risk factor for foot ulcers.  People with sensory neuropathies have impaired pain sensation and often are unaware of the constant trauma to the feet.  Neuropathy prevents people from detecting pain.  Motor neuropathy with weakness of the intrinsic muscles of the foot may result in foot deformities, which lead to focal areas of high pressure.  When the abnormal focus of pressure is coupled with loss of sensation, a foot ulcer can occur.  Common sites of trauma are back of the heel, the plantar metatarsal area, or the great toe, where weight is borne during walking.

inside the tunica albuginea (visceral peritoneum) & tunica vaginalis

        (parietal peritoneum- regulates where the testicle is in relation to body temperature, since the testicles are rested against the tunica, which rests against the abdomen, if the tunica is hit, that wave of energy will spread into the lower abdomen), muscles in abdomen control movement for thermoregulation; sperm need to be 4-5o Fahrenheit below normal body temperature
Testicles were made in the abdomen, but are held outside because sperm don’t like 98.6 body temperature, the y need to be 4-5 degrees less than this.  In the floor of the pelvis there are inguinal rings or canals that will cause the testes to descend if they haven’t already 

inflammation of the skin covering the glans penis (foreskin)…Infants with uncircumcised penises that the foreskin tore and then they wore a diaper

undescended testes, they stay in the crypt and fail to descend (incidence is increasing;

directly related to birth weight, gestational age - most children descend within 6 months (actually, 95% descend during third trimester of fetal life), if not, surgery is indicated to cause fertility problems 

In babies:
congenital defect, injury or disorder of scrotum, can also be from infections

Adults:
infectious process (e.g. gonorrhea), neoplasm, trauma to the scrotum.

condition of having functional tissue outside of uterus, very painful
 cause unknown; co-factors include:  early menarche, 27 days or less cycle, longer duration cycle, heavier flow, increased menstrual pain

Can be caused by retrograde flow of uterine cells in which it goes back through the fallopian tube instead of out through the vagina, they leak out the ovaries and implant elsewhere

ovarian cysts are quite common in women during their childbearing years.  During ovulation, a follicle (graafian follicles) grows but may fail to rupture and release

an egg.  Instead of being reabsorbed, the fluid within the follicle then persists and forms a ‘functional cyst’.  A woman can develop one cyst or many cysts (PCOS), and the majority of cysts disappear without treatment within a few months. 

Ovarian cysts are found on transvaginal ultrasound images in nearly all reproductive-age women 

Some may cause severe symptoms (pelvic pain, abnormal uterine bleeding) because of twisting, bleeding, and rupture; and some cysts may become cancerous (at least 10% of ovarian cancers start this way).

bulging of uterus into vagina (1st, 2nd, 3rd degree)

family history (may be genetic; for example, altered NRG1 [neuregulin-1] gene [a tumor-suppressor gene] is seen in over 50% of breast cancers, Edwards et al., Oncogene, October 2009); over 50 years of age (rare <25, 77% after age 50, average age = 64); “long, uninterrupted menstrual life” (early onset of menarche, having no full term pregnancy, first child after age 30, late menopause, etc); low fat diet ?, alcohol abuse ?,  over-consumption of meats that are well-done/fried, etc.

Estrogen receptors (“ER”) on cancer cells lead to better treatment outcomes -- anti-estrogen therapies (tamoxifen/Nolvadex, for example) will be more effective (ER+ cells seen in about 75% of all breast cancers); Progesterone receptors (“PR”) on cancer cells leads to better treatment outcomes --

with  nonsteroidal aromatase-inhibors like anastrozole (about 65% of ER positive cancers are also PR positive)

ERBB2 gene alteration occurs with aging, and presence of HER2 proteins means that the cancer will responed

well to Herceptin (trastuzumab) treatment in combination with other chemotherapy drugs (HER2/neu stands for

“Human Epidermal growth factor Receptor 2”, and is seen in about 30% of breast cancers).  Approximately 10
17% of breast cancers are “triple-negative”, are associated with the BRCA1 gene, and have a

poorer outcome to therapy 

Hypertrophy,dystrophy anaplasia

Human papilloma viruses need to get to the BASAL membrane to infect. If It gets to top layer it can be shed off.

1 and 2 cause plantar warts, they get worn off a lot. You can see individual cells.

In dry skin, T cells can get under infected cells and basal cells can accumulate and push the wart off.

Genital warts in mucosal tissue, mucopolysaccharides make it porous. As cell enlarges, it imbeds in basement membrane. Some genital warts can go all the way to the bone.

Most cells are so big they have vasculized and have a blood vessel in them and nerve – they have their own circulatory system and can be incredibly painful. 

Gardasil approved June 2006 - designed for HPV-6, -11, -16, & -18;

Cervarix approved October 2009 - designed for HPV-16 & -18

* BOTH are cross-protective against 31, 33, 45 for individuals without previous infection

(Malagon et al., October 2012, The Lancet - Infectious Diseases)

HSV-I when spread from cold sore; HSV II (most common; and chronic form)
Herpes Simplex Virus (HSV) (a viral pathogen)

HSV-1 chronic oral herpes = HHV-1 [cold sores = aphthous ulcers]
HSV-2 chronic genital herpes = HHV-2 [herpes genitalis]

Attach to basal cell of mucosal cells or skin cells. They are lytic viruses, unlike HPV. Causes cell to rupture and leak out proteolytic enzymes and necrose cells around and get into submucosal or dermal layers.  Once you have it you never get rid of it!! There is a protein that can stick to nerves. 

2 to 10 days.  prodromal symptoms (prior to evident ulcer outbreak) include itching, burning, tingling at the site of future lesions (viral sheading occurs during this prodromal period).  nerve involvement causes tingling, itching, and pain in the genital area, mucocutaneous replication results in small pustules and vesicles forming, which may rupture & ulcerate within five days and exacerbate the nerve irritation.  seen in cervix and urethra in 80% of women with primary infection, leading to dysuria, dyspareunia, and urine retention.  systemic symptoms include fever, headache, malaise, muscle ache, and lymphadenopathy; primary infections are debilitating.  if left untreated symptoms get worse for 10-14 days and then usually self-limit and last 2 to 4 weeks (total) during which the lesions crust over and then heal.

primary infection is defined as someone who is symptomatic but seronegative; nonprimary infection seen in seropositive individual with recurrence of symptoms.  nonprimary outbreaks are usually less severe and shorter in duration as the individual ages.  virus is shead before, during, and after (for about a month) an active lesion.