1. Gastrointestinal Diseases

2. Esophagus

3. Selected disorders of the esophagus
Motor disorders: Achalasia
Esophagitis: Reflux, infections, drugs, irradiation
Barrett’s esophagus

4. Achalasia (failure to relax)
Incomplete relaxation of lower sphincter during swallowing leading to functional obstruction and proximal dilatation
Aperistalsis, incomplete relaxation, increased resting tone
Ganglion cells of the myenteric plexus are diminished or absent
Clinical picture: dysphagia, regurgitation and aspiration
Histology: Inflammation in the area of M. plexus
Hypotheses: autoimmune, viral infections
May occur secondary to Trypanosoma cruzi infection (Chagas disease)
5% develop squamous cell carcinoma, at younger age
Loss of inhibitory innervation to the sphincter
Because it is a mechanical disorder, I have no picture for it, it is detected by the clinical picture and pressure measurement of the lower sphincter. T.Cruzi infection is a parasite that is transmitted by mosquito and leads to destruction of myenteric plexus in esophagus, stomach, colon and ureter

5. Esophagitis Reflux esophagitis Infections
Crohn disease, acute graft versus host disease
Prolonged gastric intubation
Ingestion of irritant substance
Chemotherapy and irradiation

6. Reflux esophagitis Reflux of gastric contents into esophagus
Possible etiologies: inadequate function of lower sphincter; sliding hiatal hernia
CP: “heart burn”
Complications: ulceration, bleeding, stricture, Barrett esophagus

7. Infection-induced esophagitis
More common in patients with impaired immunity
Fungal : Candida
Viruses: Herpes and Cytomegalovirus

8. Barrett esophagus A complication of long standing reflux esophagitis
Replacement of squamous epithelium by columnar epithelium with goblet cells
30- to 40-fold greater risk to develop adenocarcinoma

9. Stomach 2 1 3 1) Cardia 2) Body: Parietal and Chief cells
Parietal cells secrete acid and intrinsic factor; while Chief secrets digestive enzymes like pepsin
Gastrin stimulates the secretion of acid from parietal cells
1) Cardia
2) Body: Parietal and Chief cells
3) Antrum: Mucin secretion and G-cells that secrete gastrin

10. Selected disorders of the stomach
Gastritis
Peptic ulcers

11. Chronic Gastritis
Infiltration of the mucosa by chronic inflammatory cells (lymphocytes and plasma cells)
Causes:
Helicobacter pylori: G-ve bacilli;
Autoimmune: rare disease, autoantibodies to parietal cells (decreased acid and intrinsic factor)
Helicobacter pylori is present in 70-90% of patients with gastric and duodenal ulcers, respectively
Look for intestinal (goblet cell) metaplasia as a precancerous lesion

12. Helicobacter pylori and associated disorders
H. pylori
Gastric ulcer
Gastritis (chronic and acute), peptic (gastric and duodenal) ulcers
Gastric adenocarcinoma, intestinal type
Gastric lymphoma

13. Mechanisms of H. pylori-induced pathology
Although the organism is not invasive, it induces intense inflammatory and immune response: cytokines and B-cell activation
Enhances gastric acid secretion
Bacterial products such as urease, lipases and proteases that induce epithelial injury

14. Acute gastritis
Injury to the gastric mucosa (erosions) with no significant participation of inflammatory cells
Causes include:
Non-steroidal antiinflammatory drugs
Alcohol
Hypovolemia
Shock
Stress
Uremia
Enterogastric reflux
It is a major cause for hematemesis especially in alcoholics. 25% of presons who take daily aspirin for Rh arthritis develop acute gastritis at one point. Erosions are breach of the superficial mucosa and can heal rapidly as opposed to ulceration

15. Peptic ulcer Location: stomach or first portion of duodenum
More frequent in patients with alcoholic cirrhosis, chronic obstructive pulmonary disease, chronic renal failure and hyperparathyroidism.
Causes include: H. pylori and causes of acute gastritis (especially NSAID)
Clinical features: Epigastric pain (worse at night and relieved by food), bleeding (30%) and perforation (5%; accounts for 2/3 of deaths).
Cirrhosis: alcohol; smoking: decrease blood flow and healing, CRF and HPTH increase Ca and acid

16. Small and large bowel Developmental: Meckel diverticulum Vascular
Diarrheal disease:
Infections: viruses, bacteria, protozoa
Idiopathic inflammatory bowel disease
Malabsorption
Diverticular disease

17. Types and causes of diarrheal illness
Secretory diarrhea: loss of intestinal fluid that is isotonic with plasma and persists during fasting
Viruses: rotavirus
Toxin-mediated: Vibrio cholera, E.coli (need time)
Preformed toxin: Stapylococcus aureus (immediate effect)
Excessive laxatives
These organisms need time to proliferate within the bowel to produce their toxin, so if the symptoms appear right after eating, one should not think of those kinds of bacteria

18. Types and causes of diarrheal illness, continued
Osmotic diarrhea: secondary to intraluminal fluids with high osmolarity; it abates with fasting.
Specific therapies:
Lactulose therapy: used for constipation and hepatic encephalopathy
Gut lavage before endoscopy
Antacids

19. Types and causes of diarrheal illness, continued
Exudative diarrhea: purulent bloody stool (inflammation of the mucosa and/or hemorrhage)
Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica
Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis
Idiopathic inflammatory bowel disease
Salmonella causes half a million case of food poisoning contaminated eggs, chicken.

20. Types and causes of diarrheal illness, continued
Exudative diarrhea: pruluent bloody stool (inflammation of the mucosa and/or hemorrhage)
Infections causing tissue damage: Shigella, Salmonella, Entamoeba histolytica
Infections causing both tissue damage and toxins: Clostridium difficile; with antibiotic therapy, leading to pseudomembranous colitis
Idiopathic inflammatory bowel disease
Salmonella causes half a million case of food poisoning contaminated eggs, chicken.

21. Idiopathic inflammatory bowel disease
Ulcerative colitis
Colon only
Continuous involvement
Superficial inflammation
No granulomas
Good response to surgery
Increased risk for cancer
Crohn disease
Small bowel and colon (mostly right side)
Patchy involvement
Transmural inflammation, fistulas, strictures, serositis
Non-caseating granulomas
Poor response to surgery
Increased risk for cancer

22. Types and causes of diarrheal illness, continued
Malabsorption diarrhea (steatorrhea): voluminous bulky stool with increased osmolarity resulting from unabsorbed nutrients and excess fat; usually abates on fasting.
Malabsorption syndromes

23. Malabsorption syndromes
Defective intraluminal digestion:
pancreatic insufficiency
Defective bile secretion
Mucosal abnormalities:
Disaccharide deficiency (lactose intolerance)
Reduced surface area
Gluten-sensitive enteropathy (Celiac disease)
Surgical resection
Infections: Tropical sprue, whipple disease

24. Selected malabsorption syndromes
Gluten-sensitive enteropathy (celiac disease): 1:300 persons are affected, hypersensitivity to gliadin, a component of gluten (present in wheat flour) leading to blunted villi and increased intraepithelial lymphocytes. Increased risk for lymphoma.
Tropical sprue: malabsorption and diarrhea after a visit to the tropics. Infectious etiology, responds to antibiotics.
Whipple disease: systemic disease that affects GIT, nervous system and joints. Caused by T. whippelii (gram-positive actinomycete).

25. Clinical features of malabsorption syndromes
Hematopietic system:
Anemia: iron, folate and B12 deficiency
Bleeding: vitamin K deficiency
Musculoskeletal system:
Osteopenia: calcium and vitamin D deficiency
Endocrine system:
Amenorrhea, impotence, infertility
Skin:
Purpura: vitamin K deficiency
Dermatitis: vitamin A deficiency
Nervous system:
Peripheral neuropathy: folate and B12 deficiency.

26. Meckel diverticulum A blind pouch located in distal small bowel
The most common congenital anomaly of the small intestine; results from failure of the involution of the omphalomesenteric (vitelline) duct
The rule of 2’s:
2% of the population, 2 inches in length, 2 feet proximal to the ileocecal valve, 2 types of heterotopic tissue (pancreas and stomach); 2% are symptomatic.
Symptoms are rare:
Overgrowth of bacteria that depletes vitamin B12 leading to anemia
“Peptic” ulcer and bleeding

27. The Pancreas

28. The Pancreas 85% exocrine: enzymes for digestion
Acute and chronic pancreatitis
15% endocrine: insulin, glucagon and others
Diabetes

29. Pancreatic exocrine enzymes

30. Acute pancreatitis

31. Acute pancreatitis
Clinical presentation: abdominal pain radiating to the back, elevated serum amylase and lipase, hypocalcemia
Rise in serum lipase is more specific for pancreatitis.
Complications: infections, abscess, pseudocyst
Mortality is high: 20-40%, from shock, sepsis or acute respiratory failure, acute renal failure, disseminated intravascular coagulation

32. Chronic pancreatitis
Progressive destruction of pancreatic parenchyma and its replacement by fibrosis
Predisposing factors: alcohol, hypercalcemia or idiopathic
30% of idiopathic cases have been found to have mutation in CFTR gene
Complications: Pseudocyst, malabsorption, 2ry diabetes
Diagnosis: abdominal pain, malabsorption, calcifications on X-ray

33. Diseases of the liver

34. Liver Maintaining body metabolic homeostasis:
Lipid and carbohydrate metabolism: production and secretion of glucose
Protein synthesis: albumin, coagulation factors
Detoxification and drug metabolism
Conjugation and excretion of bilirubin
Synthesis and excretion of bile salts

35. Liver anatomy and histology
It has enormous functional reserve and regeneration occurs as long there is no extensive damage to the connective tissue framework. Surgical removal of 75% of liver produces minimal hepatic impairment and regeneration restores liver size in a few weeks

36. Patterns of hepatic injury
Inflammation
Steatosis: accumulation of fat droplets within hepatocytes
Cell death: those cells closer to the central vein are more susceptible to ischemia, toxins and drugs leading to “centrilobular” necrosis
Fibrosis: Irreversible, affect blood flow and hepatocyte function
Cirrhosis: End stage liver disease with diffuse fibrosis and regenerating nodules

37. Steatosis Alcohol Obesity Diabetes Hyperlipidemia Clinical picture:
Silent, or fatigue, malaise, right upper quadrant discomfort

38. Liver cirrhosis
Definition: bridging fibrous septa and parenchymal nodules with disruption of architecture. End stage for many diseases affecting the liver
Mechanism: cell death, regeneration and fibrosis

39. Clinical consequences of liver disease (life-threatening complications are in yellow)
Hepatic dysfunction:
Decrease synthesis capacity leading to :
Hypoalbuminemia: edema, ascitis, muscle wasting, weight loss
Hypoglycemia: weakness and syncope
Coagulation factor deficiency: bleeding
Decrease detoxification capacity leading to:
Hyperammonemia and increase toxic metabolites: Encephalopathy (altered behavior and disturbances in consciousness that may lead to deep coma and death)
Injury to other organs by active toxins
Hepatorenal syndrome:
Renal failure without intrinsic or functional causes of renal failure. ? Altered blood flow to the kidney.

40. Clinical consequences of liver disease, continued
Jaundice: yellow discoloration of skin and sclera due to accumulation of bilirubin
Cholestasis: systemic accumulation of bilirubin in addition to bile salts and cholesterol (usually secondary to obstruction)
Portal hypertension in cirrhosis: increased resistance to portal blood flow
Esophageal varices
Ascitis
Splenomegaly
Hemorrhoids
Malignancy on top of cirrhosis

41. Jaundice
Accumulation of bilirubin in tissue leading to yellow discoloration of skin and sclera (icterus)
Normal serum level: mg/dl; jaundice appears with levels above mg/dl
Source of bilirubin: the breakdown of senescent red blood cells in the spleen releases heme that changes into bilirubin by specific enzymes.

42. Bilirubin
Conjugation is a function of the liver by adding glucuronic acid to bilirubin
Unconjugated
Albumin bound
Insoluble in water, toxic
Conjugated
Loosely bound to albumin
Water soluble, non-toxic, excreted in urine

43. Laboratory evaluation of liver disease
Hepatocyte function:
Serum albumin
Prothrombin time: measuring coagulation factors (II, V, VII, X); prolonged in liver cirrhosis
Serum ammonia
Hepatocyte injury (enzymes normally present inside the hepatocytes and released with injury):
Serum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Serum lactate dehydrogenase
Biliary excretory function:
Serum bilirubin
Serum alkaline phosphatase
Serum gamma-glutamyl transpeptidase

44. Laboratory evaluation of liver disease
Searching for etiology:
Hepatitis viral antigens and antibodies
Autoimmune antibodies: for autoimmune hepatitis
Tissue iron and copper: for hemochromatosis and Wilson disease

45. Biliary disease
Secondary biliary cirrhosis: secondary to extrahepatic bile obstruction by stones, atresia or tumors
Primary biliary cirrhosis: immune-mediated destruction of intrahepatic bile ducts, more in females, presence of anti-mitochondrial antibodies
Primary sclerosing cholangitis: chronic fibrosis of intra- and extra-hepatic bile ducts; more in men, association with ulcerative colitis
Pruritis due to deposition of bile acids in skin, increased alkaline phosphatase, conjugated bilirubin, skin xanthomas due to decreased secretion of cholesterol, inadequate absorption of fat-soluble vitamins, A, D, E, K