• cytotoxic chemotherapy
• radiation therapy
• graft-versus-host disease (GVHD)

• HSV
• CMV
• fungal infections (Candida)

• Esophagitis

• sliding hiatal hernia
• alcohol
• cigarette smoking
• obesity
• CNS depressants
• pregnancy
• delayed gastic emptying
• increased gastric volume

• leukoplakia
• ulcers
•  fibrosis
• esophageal stricture which lead to dysphagia.

Barrett esophagus

- predisposed to:

- common w/

• Predisposes to: adenocarcinoma
• Common in:   males between 40 and 60

• can cause variable degrees of 
  • epigastric pain
  • nausea
  • vomiting

• aspirin
• NSAIDs
• alcohol
• cigarettes
• Helicobactter (H. pylori) infection

• presence of neutrophils in acute gastritis above the basement membrane in direct contact with epithelial cells is abnormal in all parts of the GI tract and signifies active inflammation. 
• With more severe mucosal damage, erosions and hemorrhage develop.

• loss of the superficial epithelium, generating a defect in the mucosa that is limited to the lamina propria, a thin layer of vascular connective tissue beneath the epithelium
• Hemorrhage may occur and cause dark punctae or spots like coffee grains.

Bleeding  

• Most frequent complication ; may be 1st indication

Perforation 

• Accounts for two thirds of ulcer deaths ; 

Obstruction 

• Mostly in chronic ulcers ; Secondary to edema or scarring; associated with pyloric channel ulcers ;May occur with duodenal ulcers 

Chronic gastritis

- due to:

• Cause: H.pylori inf or Autoimmune gastritis
  • Clinical of H. pylori
    • less severe but more persistent than acute
    • Nausea 
    • upper abdominal discomfort
    • sometimes with vomiting
    • hematemesis is uncommon
  • Atrophic gastritis
  • • Due to autoimmune gastritis, with a loss of parietal cell mass.
    • Clinical:
      • Leads to pernicious anemia

H. Pyloris Gastritis

- most common ulcers where?

- complications of it?

• H. pylori organisms are present
  • duodenal ulcers *most
  • gastric ulcers 
  • chronic gastritis (antrum- 90% of cases)
• Complications of H. Pyloris Gastritis:
  • Peptic Ulcer disease (also seen in chronic)
  • increases the risk of gastric cancer

Autoimmune gastritis

- characterized by

- associated with

- more common where

• characterized by 
  • (1) antibodies to parietal cells + loss of intrinsic factor +  achlorhydria 
  • (2) vitamin B 12 def - pernicious anemia. May cause atrophic glossitis and peripheral neuropathy
• Pernicious anemia and autoimmune gastritis associated with?
  •  Hashimoto thyroiditis
  • insulin-dependent (type 1) diabetes mellitus
  • Addison disease
  • Graves disease
  • vitiligo
  • myasthenia gravis
• In body of stomach; Spares the antrum + hypergastrinemia

Peptic Ulcer Disease

- due to

- location

- develops as a background to?

- what can make it work?

-clinical

• associated with H. pylori-induced chronic gastritis + NSAIDs use
• Location:
  • Duodenum >Antrum of Stomach
• Path-phys-
  • develops on a background of chronic gastritis
  • cigarette smoking (impairs blood flow to the gastric mucosa) 
  • high dose corticosteroid therapy (suppresses prostaglandin synthesis and impairs healing)
• Clinical
  • perforation, hemorrhage, and pyloric stricture (due to fibrosis)
  • epigastric pain, or aching pain
  • iron deficiency anemia may result

• Causes: nonbacterial infectious gastroenteritis
• Get it by:
  • Contaminated food or water, schools, hospitals, nursing wards, and cruise ships. 
• Clinical
  • Nausea, vomiting, watery diarrhea, and abdominal pain.

• stricture due to fibrosis and obstruction 
• inc risk to intestinal cancer

• Inflammation limited to the mucosa of colon and the superficial submucosa
• Due to: genetic factors
• Clinical
  • Crypt abscesses
  • bleeding, cramps, blood diarrhea
  • moderate anemia with moderate colitis
  • dehydration, electrolyte depletion, massive hemorrhages
• Increased risk for:
  • colon cancer. 

• Embolism or thrombosis 
• hernia intussusception
• volvulus

• Marked dilation or varicosity of hemorrhoidal venous plexus
• very common
• less common cause is obstruction of portal circulation in liver cirrhosis.

• Squamous cell carcinoma
• China-esophageal cancer belt with incidence 30-70 x greater
• distribution suggests environmental factors 
• Clinical
  • alcohol, cigarette smoking, nitrosamines, 
  • Plummer Vinson syndrome, chronic esophagitis, achalasia, esophageal stricture
  • dysphagia, cachexia, anorexia, poor survival

• In Japan, Chile, Costa Rica, and Eastern Europe the incidence = 20x higher. US rates dropped.
• Dietary and environmental factors:
  • N-nitroso compounds used w/ smocked meats or fish, pickled vegetables
• Risk inc w/:
  • H. pylori infection in chronic gastritis
  • Barrett esophagus 
  • multifocal mucosal atrophy and intestinal metaplasia
• Clinical
  • early symptoms include: dyspepsia, dysphagia, and nausea. 
  • Loss of E-cadherin

• signet-ring cell morphology
  • contain vacuoles mucin that expand the cytoplasm and push the nucleus to the periphery
• desmoplastic reaction 
  • fibrous CT that stiffens the gastric wall
• linitis plastica
  • Leather bottle appearance due to diffuse rugal thick. + rigid thick wall (from large areas of infiltration) 
• most powerful prognostic indicators for gastric cancer
  • depth of invasion + extent of nodal and distant metastasis 
• Local invasion:
  •  duodenum, pancreas, and retroperitoneum 
• Five year survival- adv gastric cancer <20 %.

• Lesions pedunculated or flat base (sessile)
• Found: 
  • colon* most
  • can be seen in esophagus, stomach, SI
• Neoplastic polyp
  • adenoma (can progress into cancer)
• Non-neoplastic polyps 
  • inflammatory
  • hamartomatous
  • hyperplastic

• benign tumor-like nodule 
• It is an overgrowth of mature cells + tissues normally present in the affected part, but with disorganization and with one element predom
• occur 
  • sporadically 
  • genetically determined
  • acquired syndromes

• focal malformations of the mucosal epithelium + lamina propria
• Clinical
  • sporadic or in clinical syndromes
  • Typically pedunculated
  • Most in the rectum
  • Most with rectal bleeding
  • Dysplasia occurs in a small proportion of juvenile polyps

 
Autosomal dominant juvenile polyposis syndrome = increased risk of colon adenocarcinoma.

• Auto dominant syndrome  
• multiple GI hamar polyps + mucocutaneous pigmentation
• Who: 
  • median age of 11
• Clinical
  • SI and pedunculated
  • Brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region. 
• Complictions:
  • increased risk of wide variety of cancers 
  • The GI adenocarcinomas arise independently of the hamartomatous polyps

• Epithelial proliferations that represent a "piling up" of goblet cells and absorptive cells
• found in:
  • People in their 60s, 70s
•  Lesions = without malignant potential

• Most clinically important neoplastic polyps:
  • colonic adenomas, benign polyps that are precursors to colorectal adenocarcinomas.

• intra-epithelial neoplasms 
• Range: small, pedun polyps to large, sessile 
• Found in: 
  • 50% of Western world by age 50 
  • no gender preference
• Three types
  • Colorectal adenomas 
  • Tubular
  • Villanous

• Men and women equal affected
•  Peaks at 60 to 70; 20 % of cases before age 50
• Etiology 
  • low fiber diet, high fat diet, high anaerobic bacterial content, genetic predisposition, Crohn disease
• Protective measures include 
  • colonoscopy, cruciferous vegetables, calcium, selenium, and aspirin (as COX-2 inhibitor)
• distributed equally over the entire length of the colon
• Colon cancer can metastasize to the lymph node, lung, liver, and brain
• Elevated carcinoembryonic antigen (CEA) is seen in about 25% of patients.

• Size 
  • ie, while cancer is extremely rare in adenomas less than 1 cm in diameter, some studies suggest that nearly 40 % of lesions larger than 4 cm in diameter contain foci for cancer
• high-grade dysplasia is a risk factor for progression to cancer.

Blood flows from the triad, through the sinusoids to the central vein; outside of lobule to inside

• the pancreatic and terminates in the ampulla 
• Vater on the duodenal surface

• glucose homeostasis
• fatty acids converted to triglycerides and secreted as lipoproteins
• amino acid metabolism

• glycogen
• triglycerides
• Fe, Cu
• lipid soluble vitamins

leak out of damaged liver cells–

• AST (Aspartate aminotransferase; SGOT); 
• ALT (alanine aminotransferase)

actively produced by damaged bile duct cells,

• e.g., alkaline phosphatase
• gamma glutamyltransferase

The majority of bilirubin comes from degradation of RBC within the macrophages of the spleen

(Hgb–>Heme–>biliverdin–>bilirubin)

• Hyperbilirubinemia, unconjugated jaundice
• due to 
  • hemolysis
  • hemolytic anemia
  • multiple transfusions 
• Path-Phys: 
  • liver can not handle the overload the excess of unconjugated bilirubin

• Hyperbilirubinemia unconj bilirubin jaundice
• due to 
  • generalized liver cell injury
  • viral hepatitis
  • drugs

• Crigler - Najjar syndrome
• Gilbert syndrome

• Hyperbilirubinemia; mix of conj/unconj bilirubin; jaundice 
• Due to:
  • hepatocellular injury
  • viral or alcoholic hepatitis
  • impairment of canalicular or ductal bile flow 

• Sustained increase in the portal venous pressure
• Due to:
  • obstruction of the blood flow somewhere in the portal circuit

Portal hypertension:

Etiology and Pathogenesis: 

• prehepatic obstruction like a thrombosis or tumors  portal vein
• intrahepatic obstruction e.g., liver cirrhosis,  hepatic shistosomiasis
• posthepatic obstruction: e.g., obstruction of hepatic vein (Budd-Chiari syndrome); compression or obstruction of inferior vena cava; severe right- sided heart failure
• acute or chronic: all produce acute or chronic passive congestion of the liver; CPC and “cardiac” fibrosis in the liver

• splenomegaly and hypersplenism
• opening of collaterals to the inferior vena cava 
• caput medusae
• ascites
• heart failure
• encephalopathy 

• Due to accumulation of fluid in the abdominal cavity which has the nature of transudate. 
• The mechanism is complex + involves:
  • increase in the portal pressure, 
  • pooling of blood in the mesenteric capillary bed
  • exudation of lymph from the liver
  • decreased oncotic pressure in association with a decrease in albumin production by the liver
  • increased renal absorption of sodium and water.

• In response to injury:
  •  viral hepatitis
  •  cirrhosis
  • toxic liver injury

• hypoglycemia, decreased production of albumin, globulin and prothrombin
• flapping tremor of the outstretched hand
• respiratory, circulatory and renal failure; 
• ascites
• peptic ulcers

• End-stage chronic liver disease resulting in destruction of normal hepatic architecture by fibrous bands that surround regenerating nodules of hepatocytes
• Results from persistent liver necrosis.

• Micronodular cirrhosis 
• involves fatty change, necrosis, Mallory bodies in the hepatocellular cytoplasm, neutrophils, and fibrosis in response to the toxic effect of alcohol. 
• The fibrosis surrounds small nodules of cells and destroys the architecture, and thus the function, of the liver.

• Micronodular cirrhosis
• Ascites, washed-out appearance, jaundice, esophageal varices, hepatic failure, heart failure, predisposition to gram negative infections, renal failure, central nervous system derangements, increased tendency for peptic ulcers, increased incidence of hepatocellular carcinoma. 
• Many patients progress to end- stage disease.

• Micronodular cirrhosis 
• Scarring interlobular bile ducts ->portal triads. 
• Primary form: 
  • autoimmune; 
  • mostly in women; 
  • both humoral and cell mediated immune destruction of tissues; 
  • 95% have anti-mitochondrial antibodies - AMA
  • fibrosis follows tissue destruction. 
• The liver is swollen and bile stained; 
• Dilated ducts may rupture and form bile lakes
• followed by inflammation and fibrosis

Biliary cirrhosis - Clinical

= what enzymes are released?

• Micronodular cirrhosis 
• Depends on the etiology and amount of tissue destruction
• Cholestasis enzymes: 
  • actively produced by damaged bile duct cells
  • e.g., alkaline phosphatase, gamma glutamyltransferase are elevated.

• Micronodular cirrhosis 
• Excessive accumulation of iron due to: 
  • 1) increased absorption from the intestine, e.g., hereditary hemochromatosis
  • 2) secondary: due to diet, supplements, multiple transfusions, hematologic disorders (thalassemia), alcoholism. 

Hereditary Hemochromatosis (HHC)

- what kind of genetic disorder

- clinical hallmark?

- complication of it?

• autosomal recessive disorder 
• accumulation in the parenchyma of the liver, heart, and pancreas
• In this disease, 20-40 g of iron may accumulate in the body
• The clinical hallmark of advanced HHC is cirrhosis (micronodular), diabetes (bronze diabetes), skin pigmentation, and cardiac failure.
•  male, 40-60
• Hepatocellular carcinoma 

Macronodular cirrhosis

- aka

- what is it

- associated w/

- increases risk of:

• AKA postnecrotic cirrhosis
• Large tracks of connective tissue surrounding more than a single hepatic lobule. 
• chronic active hepatitis /hepatotoxic agents. 
• Increased incidence of heparocellular carcinoma.

• Liver cell adenoma: rare, associated with the use of oral contraceptives. 
• Hemangioma: most common benign tumor seen in all ages

a. Hepatocellular carcinoma

b. Cholangiocarcinoma (Bile duct carcinoma)

Hepatocellular carcinoma:

- due to

- clinical

• From hepatocytes. 
• Etiology associated with 
  • history of HBV infection
  • history of HCV infection
  • alcoholic or postnecrotic cirrhosis
  • exposure to aflotoxin B
• The clinical presentation may include: 
  • hepatomegaly
  • ascites
  • portal vein thrombosis
  • occlusion of hepatic veins
  • esophageal varices
  • cachexia
  • hepatic failure
  •  elevated levels of alpha- fetoprotein (an oncoprotein).

• From biliary epithelium any where in the duct system. 
• Usually in older individuals of both sexes.

• More common than primary neoplasia 
• The liver and lungs are most often involved in the metastatic spread of cancers.
• The most common primary sources producing hepatic or liver metastases are those of the colon, breast, lung, and pancreas. 
• Any cancer in any site of the body may spread to the liver, including leukemia, melanoma, and lymphoma. 
• Typically, multiple nodular metastases are found that often cause striking hepatomegaly and may replace over 80% of existent hepatic parenchyma. Thus, metastatic tumors to the liver are a major cause of hepatomegaly.

Gall bladder - Cholelithiasis

- play role in what diseases:

- may predispose to:

• etiology of 
  • cholecystitis
  • obstructive jaundice 
  • obstruction of the common bile duct
• may predispose to carcinoma of the GB.

Gall bladder - Cholelithiasis- Etiology

- most frequently affected:

- other factors:

•  fat, female, fertile, and forty (the 4F population)
• Other factors: 
  • heredity, e.g., 75% of Pima Indian women affected by age of 25 and 90% by age of 60; 
  • estrogen- increases secretion of cholesterol and may decrease the secretion of bile acids; 
  • pregnancy-GB empties slowly in last trimester
  • obesity-via increase in biliary cholesterol secretion
  • hemolytic disease- favors pigmented stone formation (bilirubinate stones).

• Most common stones (3/4 of all)
•  If the bile contains excess cholesterol, or it is deficient in bile acids, the bile becomes supersaturated and cholesterol precipitates as solid crystals
• The stones are usually round, yellow to tan color, single or multiple and contain over 50% cholesterol

Calcium bilirubinate gall stones

- how does it form?

- associated w/?

• Composed of calcium bilirubinate (pigmented stones)
• Pathogenesis - increased unconjugated bilirubin in the bile which precipitates as calcium bilirubinate
• associated with hemolytic diseases, e.g., sickle cell anemia, thalassemia
• The stones are usually multiple and jet black in color

Brown pigmented stones

- associated w/?

• Contain calcium bilirubinate mixed with cholesterol; 
• found most commonly in the intrahepatic and extrahepatic bile ducts
• almost always associated with bacterial cholangitis in which E. coli is the predominant organism

• Bacterial infections
• chemical injury, e.g., bile stasis
• stones

Acute form:

• Abdominal pain in the right upper quadrant (RUQ)
• biliary colic
• mild jaundice
•  fever and leukocytosis
• nausea
• vomiting

Chronic form:

• presents mildly with non specific abdominal symptoms; due to chronic presence of stones; wall is fibrotic

Adenocarcinoma of the Gall Bladder:

- associated w/?

• Adenocarcinoma = most common
• F >M
• it is associated with cholelithiasis and chronic cholecystitis
• the 5-year survival rate is 3%

• Mixed exocrine-endocrine gland
• Located transversely in upper abdomen
• The head lies in the concavity of the duodenum, 
• The body includes most of the gland
• The tail ends in the hilum of the spleen
• retroperitoneal and inaccessible to physical examination
• The major pancreatic duct usually drains into the common bile duct immediately proximal to the ampulla of Vater. 
• The acinar cells (exocrine funx) synthesize some 20 different enzymes secreted into the duodenum following hormonal (cholecystokinin, secretin) and neural (vagal) stimulation
• The major hormones produced endocrine pancreas are insulin and glucagon

Acute pancreatitis

- causes:

• Starts abruptly, usually following a heavy meal or excessive alcohol intake
• Associated with alcoholism (M) or biliary disease (F)
• Middle age - peak incidence at 60 
• Pathogenesis: 
  • Injury of acini or ducts results in the release 
  • often hemorrhagic
• Causes: 
  • gallstones, bile reflux, ethanol, viruses, drugs, blunt trauma, etc. 
• Clinical: 
  • severe epigastric pain, nausea, vomiting; 
  • the enzymes enter abdominal cavity -->peripheral vascular collapse+ shock
• Elevation of serum amylase after 24-72 hrs of onset is diagnostic of acute pancreatitis.

• Progressive destruction of the parenchyma with fibrosis
• Major cause is alcohol abuse. 
• Chronic calcifying pancreatitis is the most common form. 
• Presents with persisting abdominal pain radiating to the back. 
• Complications include diabetes, malabsorption, weight loss.

Pancreatic Neoplasms:

Benign

Pancreatic Neoplasms - malignant like Adenocarcinoma

- high incidence among

- etiology

-pathogenesis

- clinically:

• male in younger groups; same male: female incidence older; highest incidence in NZ among the Maoris; USA - Native and African 
• Etiology
  •  smoking (it is dose-dependent)
  •  exposure to chemical carcinogens
  • high dietary fat consumption
  • diabetes mellitus
  • chronic pancreatitis
• pathogenesis 
  • k-ras mutations, overexpression of erbB2, deletions on chromosome #18
• Most frequent location is in the head (60%)
• Clinical: 
  • weight loss, pain radiating to the back, jaundice
  • biliary obstruction due to tumor in head (more symptomatic)
• Half of the patients die within 6 weeks of diagnosis; the 5-year survival rate is 1%. 

• Zollinger-Ellison syndrome from G cells
• secrete gastrin
• may be benign but the majority are malignant; 
• associated with increased gastric hypersecretion and peptic ulceration

• Neurologic disorders: confusion, lethargy, coma, personality changes 
• Ascites 
• Peptic ulcers
•  Respiratory, circulatory and renal failure (hepato-renal syndrome)

• Function: Stores, concentrates and releases bile (conjugated bilirubin, bile salts, phospholipids, cholesterol) 
• Cholelithiasis: Stones within the lumen of the gall bladder or extraheptic biliary tree 
• Common Types: Cholesterol, Calcium bilirubinate
• Cholecysitis: Acute or chronic inflammation of the gall bladder 
• Etiology: bacterial infections, chemical injury, stones 
• Neoplasms 
• Benign tumors are rare 
• Adenocarcinoma is the most common malignant tumor (F>M)

• Normally a person has 3 to 4 g of iron, 2/3 of which is in the form of Hgb; 
• the rest is stored as soluble feritin in the cytoplasm of all cells
• most of the iron storage is in the bone marrow and liver
• Hemosiderin is a product of degradation of feritin; it is insoluble.

• Secondary form: 
  • extrahepatic biliary obstruction associated with gallstones
  • cancer
  • external compression by enlarged lymph nodes
• The liver is swollen and bile stained; 
• Dilated ducts may rupture and form bile lakes
• followed by inflammation and fibrosis

• Neoplasia - results in hypersection
• hyperplasia  - results in hypersection
• Hemodynamic alterations
  • hemorrhage, necrosis 
  •  results in hyposection
• Congenital disorders
  • e.g., aplasia, hypoplasia
  • results in hyposection 
• Inflammation 
  • results in hyposection
• Pressure from adjacent 
  • tumors results in hyposection

• Dysphagia
•  Hoarseness
•  Congestion of the head and neck veins 
• T4 and T3 levels are normal 
• TSH levels are usually normal

• Elevated body temperature, heat intolerance, perspiration 
• Increased cardiac contractility: direct effect on fibers 
• Increased blood volume via renin/angiotensin pathway 
• Elevated heart rate and systolic pressure; increased cardiac output

• Irritability 
• Tremor of hands 
• Weight loss 
• Muscle weakness

Due to bacterial or viral infections from the pharynx or upper respiratory tract

Transient hypothyroidism

• Mineralocorticoid - hormones similar to aldosterone (thus, retain water and salt)
• Glucocorticoids - aka cortisol: inc sugar in blood, suppress immune system, dec bone formation
• Sex hormones

• Making glucose from non carb, deposition of glycogen
• Break down of fats
• Gastric secretion 
• Bone resorption 
• Neural excitability 
• Suppress immune functions

• Adenoma of the cortex of adrenal gland(90%)
• Hyperaldosteronism
• Clinical
  • Hypertension 
  • Potassium loss: muscle weakness, cardiac arrhythmias, paresthesia, renal tubular degeneration 
  • Renal damage: polyuria

Waterhouse-Friedrichsen Syndrome

- due to?

- clinically seen:

• Acute form of Adrenal cortex Hypofunction
• Etiology:
  • Abrupt withdrawal of corticosteroid therapy 
  • Hemorrhage into the gland
  • Extensive burns
  •  Infections (Meningococcal septicemia)
• Clinical
  • sudden hypotension
  • shock
  • fever
  • purpura
  • DIC (disseminated intravascular coagulation)

 Addison disease

- what is it

- cause by:

• Chronic form of Adrenal Cortical Hypofunction 
• Hypoaldosteronism
• Caused by:
  • Autoimmune
  • Tuberculosis:
• Clincal
  • hypotension
  • hyperpigmentation
  • weakness, weight loss
  • GI symptoms- like diarrhea

Pheochromocytoma

- what is it

- may be apart of:

• Hyperfunction of the Adrenal medulla
• Benign tumor - episodes sporadically
• Catecholamine overproduction 
• Clinical
  • Paroxysmal hypertension 
  • Tachycardia Sweating, trembling, anxiety
  • severe throbbing headache
  • sudden death from MI or stroke
  • May be part of MEN 1 and 2 syndromes

• usually benign, like adenomas
• But significant for 3 reasons: 
  • 1) size- pressure on adjacent structures, 
  • 2) hypersecretion of hormones
  • 3) destruction of gland tissue.

• Benign tumor of pituitary gland
• Hyperpituiary - too much prolactin
• clinical: 
  • female — amenorrhea, galactorrhea, infertility;
  •  male— decreased libido and impotence
  • due to prolactin inhibiting gonadal sex hormones

• Hyperfunction of Pituitary gland due to tumor
• Tumors secrete growth hormone (GH);
• Clinical: 
  • in children, see gigantism because b4 epiphyses close
  •  in adults, after epiphyses have fused, tumor results in acromegaly
• Clinical of Acromegaly:
  • coarse facial features with broadening of the lower face
  • overgrowth of the mandible (prognathism) and maxilla
  • spaces between the upper incisors
  • large hands and feet

• secondary (not primary) diabetes
• decreased glucose tolerance
• hypertension 
  • can lead to LV mass and congestive heart failure
• Thyroid, liver +adrenals = can also enlarge 

• hyperfunction of the pituitary gland due to tumor
• hypersecretion of ACTH 
  • stimulates the adrenal to produce excess of cortisol (Cushing’s disease which results in Cushing Syndrome)) 

Craniopharyngioma

- what is it

- what needs to be present clinically?

• Suprasellar Hypofunction of the pituitary gland
• Seen in :children and young adults; older adults 
• due to destruction of pituitary proper or the hypothalamus due to large tumor size
• Clinical: 
  • impinging on the optic chiasma results in impaired vision
  • headaches
  • growth retardation
  • Diabetes insipidus (from posterior pituitary) results in ADH deficiency

Post-partum necrosis

- what is it

- aka

• Hypofunction of the Pituitary gland
• Due to loss of blood to PG (causing necrosis) after woman gives birth
• AKA Sheehan SYNDROME
• Anterior PG more affected than Posterior PG

• Hypofunction of the Pituitary gland
• Due to congenital disease causing lack of GH (during time when epiphyses have not closed)

• Hypofunction of the Pituiary Gland/ Hypothalamus
• due to deficiency of ADH (secreted by the posterior pituitary; under the influence of the hypothalamus) 
• Clinical presentation: 
  • polyuria
  •  polydipsia
  • (no polyphagia as in DM)

• Originates from endoderm at root of tongue and descends to its normal position in the anterior neck
•  Remnants of tissue in the path of descent can result in thyroglossal (duct) cysts, or ectopic glands
• T 3 (major effector) + T 4 cause increased O2 consumption in tissues, affect all tissues, and increase both anabolic and catabolic functions
• C cells: secrete calcitonin (decreases Ca concentration).

• Non-toxic goiter when there is no change in T3/ T4 levels!!
• Cause:
  • Impairment of iodine utilization
  • exaggerated response to TSH
  • autoantibodies
  • dietary goitogens
• T3 normal; T4 normal; TSH normal
• Clinical
  • dysphagia
  • dyspnea
  • hoarseness
  • congestion of the head and neck

Virtually all long standing simple goiters convert to multinodular goiters, which are:

Dental issues:

•  thyrotoxicosis (toxic multinodular goiter with elevated thyroid hormone levels)
•  Extreme enlargement due in part to 
  • intermittent periods whereby dietary iodine increases
• When demand for thyroid hormone decreases:
• the stimulated follicular epithelium and the thyroid follicle involute
• Dental management- use of epinephrine  to patients with thyrotoxicosis. 

• Inc in T3 and T4; presence of toxic goiter
• state of hypermetabolism and hyperactivity
• All cases of hyperthyroidism present with:
  • elevated body temperature
  • increased cardiac output due to decreased systemic vascular resistance
  • increased blood volume through activation of the renin-angiotensin system
  • increased cardiac contractility
  • and elevated heart rate and systolic pressure
  • heat intolerance
  •  continuous perspiration
  •  marked irritability and tremor of the hands
  • weight loss but increased appetite
  • and muscle weakness.

• Hyperthyroidism with goiter
• due to Autoimmune antibodies activating TSH receptors in Thyroid; heredity, sex, emotional factors.
• Clinical:
  • goiter 
  • hyperthyroidism 
  • exophthalmos 
  • pretibial myxedema of the skin
  • thyroid follicles are filled with colloid
  • Histologically,  too many cells. 
  • increase uptake of iodine by the thyroid (reflective of increased thyroid hormone synthesis) 
  • elevated serum levels of T3 and T4

• Hyperfunction of the thyroid gland
• due to benign tumor causing enlargement of one solitary part of the gland
• clinical
  • hot nodule
  • milder than Graves 
  • symptoms do not present until the tumor is large
  • not dependent on TSH

Due to:

• defective synthesis of TH 
• inadequate functioning of thyroid parenchyma as a result of thyroiditis or surgical resection
• inadequate secretion of TSH 

Clinical symptoms depend on the degree of hypofunction of the gland.

• Hypothyroidism in childhood
• Lack of T3, T4 due to 
  • errors in hormone synthesis
  • unresponsiveness to TSH
  • thyroid dysgenesis 
• Clinical: 
  • cretins are dwarfs
  • ossification, epiphyseal union, and dentition formation abnormal
  • enlarged protruded tongues
  • large abdomen
  • low body temperature; pale cold skin
  • mental retardation
  • serum levels of TSH elevated and low serum levels of T3 and T4.

Myxedema

• Hypothyroidism in adults
• Lack of T3, T4 due to:
  • may be of autoimmune origin
  • end stage of Hashimoto’s disease (autoimmune hypothyroidism)
• Clinical
  • myxedema, e.g., boggy facies,  puffy eyelids, edema of hands and feet, enlarged tongue, hoarseness
  • decreased cardiac contractility, prolonged diastolic relaxation, decreased heart rate
  • Myxedema heart- results in decreased cardiac output; may lead to pericardial effusion
  • atherosclerosis
  • Cardiac tamponade apparently does not occur.

• Hypothyroidism 
• due to autoimmune
• Clinical: 
  • Initially - Euthyroid state
    • gland often diffusely enlarged, painless, symmetric, and rubbery
  • Eventually - Atrophied hypothyroid state
    • lymphocytic infiltrates, plasma cells, and well developed germinal centers
  • Women

• Thyroid epithelial cells (thyrocytes) produce thyroid globulin
• This is subsequently iodinated and stored as thyroid hormone in the colloid containing follicles of the thyroid gland
• Sensitization of autoreactive CD4+ T cells to thyroid antigens appears to be the initiating event for thyroid cell death  
• In the usual clinical course of Hashimoto thyroiditis, the hypothyroidism develops gradually
• In some cases, may be preceded by transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones
• During this secondary phase, T3 and T4 levels are thus elevated, TSH is diminished, and radioactive iodine uptake is decreased. 
• As hypothyroidism supervenes, however, T3 and T4 levels progressively fall, accompanied by a compensatory increase in TSH—reflective of a decrease in the biosynthesis of thyroid hormone. 

Subacute thyroiditis

- aka

- due to

• Hypothyroidism 
• aka Granulomatous/De Quervain
• due to:
  • viral infections from pharynx and upper respiratory tract 
    • Coxsackievirus, mumps, measles, adenovirus
•  Clinical
  • transient (gone after 2-6 weeks)

• Hypothyroidism aka Papillary carcinoma
• due to non-functional carcinoma
  • possibly from exposure to ionizing radiation
• Clinical
  •  (“cold nodules”) 
  • form solitary nodules
  • can destroy the gland
  • usually slow growing and are slow to metastasize
  • women
  • Hoarseness, dysphagia, cough, or dyspnea suggests advanced disease
  • In a minority of patients, hematogenous metastases are present at the time of diagnosis, most commonly in the lung.

• consists typically of 4 glands on the posterior surface of the thyroid
• PTH regulates calcium and phosphate metabolism: 
  • bone-increases bone resorption; 
  • kidney-decreases phosphate reabsorption with resulting phosphaturia, enhances calcium reabsorption, and increases vitamin D production in the kidney; 
  • intestine- increased absorption of calcium due to enhanced vitamin D production. 
  • Vitamin D regulates serum calcium.

Primary

• usually due:
  • Adenoma- accounts for 85% to 95 % of cases. 
  • Hyperplasia--all glands are enlarged and hypercellular and occurs in 15% of cases. 
  • Carcinoma-rare

Secondary

• usually due to:
  • kidney failure
  • intestinal disease
  • renal cell carcinoma

• Renal disease: 
  • inability of kidney to secrete out phosphate
  • initially, hypocalcemia
• vitamin D deficiency
• malabsorption

Clinical of Secondary -  

• hyperplasia of all four parathyroid glands 
• compensatory hypersecretion of PTH

• Due to renal failure
  • kidney can't excrete phosphate (hyperphosphatemia)
  • Pt becomes hypocalcemic initially 
  • Pt can't make active Vit D either 
• The Hypocalcemia:
  • Results in parathyroid starts to secrete PTH
• Inc of PTH:
  •  osteoclasts are recruited to resorb bone -osteoporosis in bone 
  • Cystic lesions due to  osteoclast-mediated resorption-  osteitis fibrosa cystica
• Calcium rises in blood. But phosphate still can't be excreted into urine.
  • Elevated levels of serum phosphate are “driving force” 
  • Serum phosphate directs the elevated levels of serum calcium  back into the bone 
    • osteosclerosis, or thickening of the bone
• Result of less active Vit D
  • osteomalacia
• renal osteodystrophy (changes in bone due to secondary hyperpara in renal failure)
  • Osteoporosis
  • osteitis fibrosa cystica 
  • osteomalacia
  • osteosclerosis 
  • Bone likely to fracture

Hypoparathyroidism

- what is seen clinically

• Due to accidental removal of glands during surgery
• Clinical:
  • All produce depressed serum calcium and elevated serum phosphate. 
  • tetany, laryngeal spasms, neuromuscular irritability, cataract formation
  • Tetany, neuromuscular irritability, is the hallmark of hypocalcemia.

• Hyperfunction of the Adrenal Cortex
• due to 
  • functional adenoma in pituitary gland; inc in ACTH
  • adenoma/carcinoma in the adrenal cortex; Inc of cortisol secretion
  • Paraendocrine tumors (cancer in lung that secretes ACTH)
  • Exogenous source: chronic glucocorticoid drug therapy
• Clinical
  • moon face, buffalo hump, 
  • edema, hypertension (due loss of Na)
  • muscular weakness (due to loss of K)
  • increased susceptibility to infection
  • diabetes mellitus due to increased gluconeogenesis and glucose intolerance
  • osteoporosis
  • violaceous striae (purple striae on skin)
  • easy bruising 
  • congestive heart failure
  • atherosclerosis (due to inc fat metabolism)
  • gastric ulcers (inc in gastric secretions)

•  Hyperaldosteronism in Adrenal Cortex
• due to excess of aldosterone produced by adenoma of the cortex (90%) but bilateral hyperplasia cases are increasing
• Clinical--
  • hypertension -sodium reabsorption and water retention leads to 
  • hypokalemia leads to muscular weakness, cardiac arrhythmias, paresthesia (numbness); 
  • renal damage--polyuria due to lack of response to ADH due to tubular degeneration.

• Hyperfunction of adrenal cortex that deals w/ sec hormones
• Get: excess of androgenic hormones
• May be seen with or without Cushing syndrome.

INC production of Ca2+

DEC production of Phosphate

• exophthalmos (enlargement of extraocular muscles within the orbit, due to mucinous edema [due to accumulation of proteoglycans or mucopolysaccharides], fibroblast, and lymphocytic accumulation); 

whereby the skin is thickened and scaly (due to infiltration with glycosaminoglycans or proteoglycans, and lymphocytes)

• hypercalcemia + hyophosphatemia
• Inc bone resporption
  • Osteoporosis
  • Osteitis Fibrosis Cystica w/ Brown tumors
  • Loss of lamina dura
• Metastatic calcifications
  • nephrocalcinosis = kidney stones
  • cataracts (calcium in eye)
• PTH stimulates secretion of Gastrin hormone
  • peptic ulcers

• It is not a single disease 
• It is a group of metabolic disorders sharing the common underlying feature of hyperglycemia
• Chronic hyperglycemia may be associated with secondary damage in multiple organ systems

• normal-70 to 109 mg/dL 
• Impaired fasting glucose, or “Pre-diabetes”, 110—125 mg/dL 
• Two HBA1c tests greater than 6.5%. 
•  A fasting glucose > 126 mg/dL 
• A random glucose > 200 mg/dL
• OGTT), in which the glucose is > 200 mg/dL

• (primary diabetes) 
• is characterized by an absolute deficiency of insulin caused by pancreatic Beta-cell destruction
• It accounts for approximately 3% to 5% of cases.

• (primary diabetes) 
• is caused by a combination of peripheral resistance to insulin action and an inadequate secretory response by the pancreatic Beta-cells 
• Approximately 95% of patients have type 2 diabetes

• occurs in approximately 4 % of women during pregnancy 
• insulin resistance caused by placental hormones

•  kidneys, eyes, nerves, and blood vessels

Pathogenesis of Type 1 DM

- pathogenesis, genetic suscept, env suscept

• autoimmune (Type IV immune response) 
• islet destruction is caused primarily by T lymphocytes, reacting against as yet poorly defined Beta-cell antigens, or fragments of endogenous insulin
• Genetic susceptibility—class II MHC (HLA) locus on chromosome 6p21 (HLA-D) 
• Environmental factors—CMV, Coxsackie virus B

• The two metabolic defects:
  • (1) a decreased ability of peripheral tissues- insulin resistance
  • (2) Beta-cell dysfunction that is manifested as inadequate insulin secretion
• Insulin resistance -  loss of function of the insulin receptor, loss of intracellular signals

• Profound hyperglycemia – diabetic coma 
• Ketoacidosis (KDA)—life threatening 
• Insulin shock—too much insulin, not enough food, increase in exercise, or a combination thereof—life threatening

• Placenta produces hormones to sustain pregnancy; these hormones (cortisol, progesterone, prolactin) make cells resistant to insulin
• and as the placenta grows larger during the second and third trimesters, it is even harder for the maternal insulin to work effectively—insulin resistance 
• mother may need three times as much insulin to control her blood sugar 
• fetal pancreas to make extra insulin; the maternal insulin does not cross the placenta; however, the maternal glucose does 
• the extra energy is stored as fat—macrosomia or a “fat” baby 
• obesity and adults who are at risk for type 2 diabetes 

• Macrovascular disease—large and medium-sized muscular arteries 
• Microvascular disease—capillary dysfunction in target organs 
• Macrovascular disease causes - accelerated atherosclerosis ,MI, stroke, and lower extremity gangrene 
• Microvascular disease causes retinopathy, nephropathy, and neuropathy

• Control of blood sugar - delays microvascular disease
• Chronic hyperglycemia leads to microvascular complications (eye, kidney, nerve) 
• Control of blood pressure and cholesterol, -- macrovascular disease, MI and stroke.

• form as a result of nonenzymatic reactions between intracellular glucose and cross-linking with extracellular matrix proteins
  • i.e., collagen and laminin
• are resistant to proteolytic digestion. Thus, cross-linking decreases protein removal while enhancing protein (collagen) deposition, e.g., thickening of basement membrane, as in diabetic nephropathy
• AGE-modified matrix components also trap, e.g., LDL. In large vessels (the aorta), trapping of LDL retards its efflux from the vessel wall and enhances the deposition of cholesterol in the intima, thus accelerating atherosclerosis.

• Fasting Blood Sugar 
• Glycosylated Hemoglobin (HbA1c)
  • 4 month assessment - target 7%
• Postprandial (post-meal) blood sugar
  • one to two hours
  • hyperglycemic spikes
  • may be associated in the long term with chronic renal failure

CYE HAReee

• 
  
• Infectious mononucleosis (EBV) can cause mild hepatitis during acute phase 
• Cytomegalovirus (CMV) infection in newborn or immunosuppressed 
• Yellow fever (yellow fever virus) important in tropical countries
•  Others: adenovirus, rubella, enterovirus, herpesvirus infrequently cause this in children and immunosuppressed

• Symptomatic vs asymptomatic 
• Constitutional symptoms: anorexia, nausea, vomiting, fatigue, myalgia, arthalgia, headache, photophobia, pharyngitis, cough, coryza 
• May precede jaundice by 1-2 weeks 
• Dark urine and clay colored stools 
• Low grade temp
• Change in smell and taste 
• Weight loss

• clinical prodrome diminish 
• Liver increases in size and is tender – hepatomegaly with RUQ pain 
• Elevation in AST, ALT, alkaline phosphatase, bilirubin 
• Level does not correlate with liver damage 
• Bilirubin > 2.5 mg/dL 
• Neutropenia and lymphopenia transient then lymphocytosis 
• Drop in albumin is rare in acute

• ss RNA 
• Hepatovirus, related to picornavirus 
• Incubation 2-4 or 3-6 weeks 
• Contaminated food or water 
• Fecal-oral spread, rare sexual 
• No chronic carrier state so no chronic liver disease 
• Cellular immunity: CD8+ T cells create injury 
• Diagnose with anti-HAV antibody 
• Protect with vaccination

• Vaccine or IG 
• Immunoglobulin IG usually used in patients who are immune compromised 
• Patients with other hepatitis infections should be vaccinated

Clinical outcomes possible: 1-5 

• 1) Acute recovery and clearance of surface Ag 
• 2) Non-progressive chronic disease 
• 3) Progressive disease, to cirrhosis 
• 4) Fulminant hepatitis
•  5) Asymptomatic carrier 
• *chronic disease necessary for progression to hepatocellular carcinoma

• Partial ds DNA 
• Incubaton 4-26 weeks, average 8 weeks 
• 42 nm virion is spherical double stranded 
• “Dane particle” 
• Contains outer surface envelope of protein, carbohydrate and lipids containing 28 nm hexagonal electron dense core 
• Parenteral, sexual, perinatal transmission 
• Diagnose: HBs Ag or anti-HBVc antibody 
• 10% chronic disease 
• Prevent with HBV vaccine 
• Nucleocapsid core protein: HBc Ag = Hepatitis B core Antigen remains in hepatocyte 
• Envelope glycoproteins: HBsAg = Hepatitis B surface Antigen 
• Longer polypeptide precore + core antigen known as HBeAg or Hepatitis B e Antigen; measures ‘infectivity’ since directed into blood 
• *DNA polymerase for reverse transcriptase activity 
• *HBV- X needed for replication (transcriptional transactivator) 
• Presence in hepatocytes does not cause damage 
• Damage is by CD8+ cytotoxic T cells on virus infected cells 
• Vaccine: HBs Ag is grown in yeast cells; injected to stimulate antibody production in series of 3 shots 
• Vaccine cannot cause disease

• HBs Ag 
• Appears before symptoms 
• Peaks during overt disease 
• Disappears in 3-6 months 
• PERSISTS IN CARRIER 
• Anti-HBs is HB surface antibody 
• Seen after acute disease 3-6 months after HBs Ag disappears 
•  LIFELONG PROTECTION usually

• Circular defective ss RNA 
• Defective sub viral particle in Deltaviridae family 35 nm 
• HD Ag (delta Ag) resembles HBV 
• Incubation 4-26 weeks 
• Parenteral transmission 
• Diagnose with IgM + IgG antibodies, HDV RNA serum, HD Ag in liver 
• IgM anti-HDV antibody shows recent infection
• Co-infection when HBV and HDV infection occur together; 5% chronic disease 
• Super-infection when HBV infection is followed by HDV, less than 70% chronic disease 
• HB vaccine prevents B+D

• ss RNA virus
• Flaviviridae family I
• ncubation 7-8 weeks 
• Parenteral transmission, intranasal cocaine is risk factor 
• 80% chronic liver disease 
• Diagnose with PCR for HCV RNA; 3rd generation ELISA for antibody detection 
• No vaccine

• ss RNA Calcivirus 
• Fecal-oral 
• Incubation 4-5 weeks 
• No chronic disease 
• Diagnose with PCR for HEV, IgM and IgG anti-HEV Ab 
• Zoonotic disease with animal reservoirs: monkeys, cats, dogs, pigs 
• 20% mortality in pregnant patients

• PAN: polyarteritis nodosum is systemic necrotizing vasculitis of medium or occasionally small muscular arteries 
• Segmental transmural inflammation 
• Affects middle aged or older adults 
• Pathogenesis: idiopathic 
• Some occur in HBV especially IVDU, HCV, hairy cell leukemia 
• In HB, immune complexes may play a role

• Mononeuritis with motor and sensory deficits 
• Asymmetric 
• Progress to branches 
• Renal involvement is common 
• HTN may develop 
• Skin lesions and motor weakness (wrist or foot drop) 
• No diagnostic lab test 
• Dx by biopsy 
• Arteriogram see microaneurysms and abrupt cut off 
• Rule out other diagnoses based on organ involvement and absence of other antibodies like ANCA, anti smooth muscle Ab seen in other diseases

Addison Dz

Crigler Najjar Syndrome

Gibert syndrome

Dubin-Johnson SyndromeBlack liver

Rotor's Syndrome

CONJUGATED bili

found in alcoholic hep/ cirr

Wilson Dz

Biliary cirrhosis

hep carcinoma

small intestine

Pedunculated

Auto dom.

Multiple GI hamar polyps and MUCOTANEOUS Pigmentation!!

Not neoplastic!!

but it inc risk to bunch of cancers (like PANCREATIC CANCER)

non caseating granuloma

Skip lesions (cobblestone appearance) 

Fistulae

Creeping fat

Earliest lesion- APHTHOUS ULCER

loss of E caderin

signet cell ring

Linitis plastica (thickening wall, leather

also des... wall

tetany

laryngeal spasms

neuromus irrit

cataract formation

• muscle weakness
• cardiac arrhythmias
• paresthesia
• renal tubular degeneration 

predominantly in the rectosigmoid colon. 
large
(sessile)
elevated lesions
60 % are larger than 2 cm in diameter; 
commonly 1/3 of villous adenomas contain foci of carcinoma 
higher potential for malignant transformation to colorectal carcinoma than tubular adenomas