This document provides an overview of pathophysiology concepts including biopsy, growth disorders, cell injury, and inflammation. It can be summarized as: 1) Biopsy is the use of diseased tissue or cells for diagnostic purposes, including different types of tissue and cell biopsies. 2) Growth disorders include increased growth like hypertrophy and hyperplasia, decreased growth like atrophy, and abnormal cell differentiation like metaplasia and dysplasia. Cell injury can be reversible or irreversible and cause cell death through necrosis or apoptosis. 3) Inflammation is characterized by redness, heat, pain, swelling, and loss of function, and involves processes like increased blood flow and the migration

26. Healing by 2 nd intention Healing by 1 st intention The 2 ends are non approximated The 2 ends are approximated Infected wound Clean wound Necrotic tissue is found No necrotic tissue No tissue depris Tissue depris Long time to be healed Short time to be healed Much larger scar Small scar Granulation tissue is the first Epithelial growth is the first

30. 3 Clinical stages of HIV (1) Acute phase stage: (2)Asymptomatic stage(Latent phase) (3) Symptomatic or (AIDS stage) - 2-4 weeks after infection. - Symptoms of acute illness.(Fever,fatigue …) -Transient reduction of CD8+, CD4+ number. -Symptoms disappear later  asymptomatic - Long period 5-10 years) free of infection symptoms. - Slow persistent destruction of immune cells  decrease number of circulating CD4+ lymphocytes and CD8+ lymphocytes - Marked decrease in CD4+ lymphocytes -AIDS-related complex (ARC): fever, night sweats, diarrhea and * opportunistic infections 1- Tumors: Kaposi' sarcoma 2- Neurologic: dementia complex Loss of memory ,

33. Spread of malignant tumours Local (Direct) spread : - Aided by loss of cell cohesion . - Along lines of least resistance . Distant spread : 1- Lymphatic spread: -Lymphatic embolism . Groups of cell travel through lymphatics to regional L.Ns. -Lymphatic permeation . Tumors cells grow within lymphatics as solid cords. 2- Blood spread: 3- Transcoelomic spread: peritoneal cavity, plleura, pericardium, ventricular system of the brain.

37. Clinical Uses of Tumor Markers • Screening for cancer (Alfa feto protein for liver cancer) • Diagnosing cancer – (pelvic mass) • Evaluating prognosis of cancer- (CEA in colon cancer) • Tumor staging - • Detecting Tumor Recurrence or remission - • Localizing tumor and directing chemo- or radio-therapeutic agents- • Monitoring the effectiveness of cancer therapy

38. Hormones of the Pituitary (A) Hormones of anterior pituitary 1- Growth hormone (GH). Stimulates growth of long bones, organs and muscle during development 2- Adrenocorticotrophic hormone (ACTH). Stimulates the adrenal cortex to produce adrenal hormones such as cortisol 3- Thyroid-stimulating hormone (TSH). Regulates secretion of thyroid hormones T 3 and T 4

41. Hypopituitarism: *-Decreased activity of the pituitary gland due to hyposecretion of one or more pituitary hormones. - If all pit.hs. are lacking,  panhypopituitarism . *-Manifestations are highly variable and depend on the hormone or hormones that are lacking . Etiology : Pituitary damage due to: 1- Trauma. 2- Infection. 3- Ischemia. 4- Tumors.

42. Disorders of the anterior pit. gland Growth hormone hyposecretion Manifestations  In children :  short stature ( dwarfism ).  In adults :  Muscle weakness and obesity . Treatment: GH replacement therapy

43. Growth hormone hypersecretion 1- Gigantism  results from the excess production of GH before fusion of the epiphyseal plates of the long bones (around puberty). * Manifestations : Extremely tall stature due to excessive growth of the long bones . 2- Acromegaly  GH excess occurs after fusion of the epiphyseal plates of the long bones . * Manifestations : Overgrowth of C.T. , Bones grow more in width than in length  patients presented with thickening and deformation of the hands, face, skull and feets. 3- C.N.S. disturbances (headache, vision changes). 4- C.V.S. disease: As(hypertension , coronary artery disease). Treatment Surgical removal of tumor. Radiation therapy of the tumor if surgery is not feasible .

44. Disorders of the posterior pituitary A- Increased Production of ADH . - Caused by pituitary tumors or injury or transiently due to physiologic stress. Manifestations  Excessive fluid retention  Generalized oedema (Weight gain).  Incrased in serum sodium level. Treatment  Fluid restriction.  Diuretics.  Removal of tumor if present

50. Hyperthyroidism - It is hyperfunction of the thyroid gland due to over secretion of thyroid hormones. Causes : 1- Primary hyperthyroidism : Overactive gland ( Grave’s dis . Or secondary toxic goiter or functioning adenoma or carcinoma). 2- Secondary hyperthyroidism : a- Excessive stim. of thyroid by excess TSH (Pit.Tum.) or b-By tumour outside thyroid gland that produce thyroid hormones or TSH ( paraneoplastic syndromes)

53. Diabetes mellitus Risk Factors for Diabetes Mellitus 1 . Obesity. 2.Familial history of diabetes mellitus. 3.Increasing age. 4.Dietary factors.

54. Types of diabetes mellitus Type I diabetes (insulin-dependent diabetes ).  Due to progressive autoimmune destruction of the pancreatic  cells, idiopathic, or following viral infections.  'Little or no insulin secretion occurs . Manifestations: 1-Hyperglycemia. 2- Weight loss. 3-The three "polys“. - Polydypsia, (increased thirst), - Polyphagia (increased appetite), - Polyuria (increased urine output )

56. Type II diabetes mellitus (non-insulin-dependent diabetes) 1- More than type I diabetes. 2 -Unknown cause. 3-There is "insulin resistance," (lack of responsiveness by tissues and the pancreas itself to insulin). 4-Abnormalities of insulin receptors, intracelluar signaling pathways or glucose transporters. -Increased levels of free fatty acids-)stimulate insulin secretions and inhibit glucose uptake by tissues

57. Mechanisms of Tissue Injury in Chronic Diabetes Mellitus 1- Glycosylation of proteins : Attachment of glucose to proteins in the eye, blood vessel walls, and kidney membranes  change their structure  altered function and eventual damage of these tissues 2- Formation of alcohol sugars (example: sorbitol )  do not easily diffuse out of tissues  swelling and damage of tissues. 3- Poor blood flow and oxygen delivery to tissues :  reduce overall blood flow to tissues  ischemic injury.

58. Long-term complications of diabetes mellitus 1. Diabetic neuropathy : is due to ischaemia . 1-Abnormality of nerve conduction and function, affects peripheral nerves. 2-Numbness, pain or sensory /motor impairment. 2. Diabetic nephropathy  Thickening of the glomerular basement membrane and glomerulosclerosis due to trrapping of Glycosylated protein in the glomeruli  Glomerular filtration decreases  albuminuria

59. 3 . Vascular disease 1-Coronary artery disease, cerebrovascualr disease and peripheral vascular injury due to:elevated serum lipid levels,enhanced atherogenesis (formation of athero-sclerotic leions). 2-Peripheral vascular disease  gangrene and amputations (particularly of the toes and feet). 4.Impaired healing and increased infections risk due to poor blood flow -  limits the delivery of leukocytes and oxygen to the injured area  ) impairing removal of debris and infectious organisms.  The high glucose levels serve as a nutrient to support the growth of microorganisms .

61. A- Genetic Defects 1-Hemophilia: Caused by a genetic deficiency or lack of certain clotting factors . Type A hemophilia :  Most common form (80% or more).  X-linked recessive disorder Results from a deficiency of clotting factor VIII (8). Type B hemophilia (Christmas disease):  Second most common form of hemophilia (10 to 15%)  X-linked autosomal recessive disorder.  Results from a deficiency of clotting factor IX (9) Type C hemophilia (Rosenthal's disease):  Least common of all hemophilia cases (<5%).  Results from a deficiency of clotting factor XI (11).  Autosomal recessive disorder.

62. Manifestations of hemophilia  May present as a-mild, moderate or severe bleeding disorder depending on the activity of the clotting factors  Excessive bleeding with trauma or surgery.  Bleeding into soft tissues, muscles and joints. Treatment of hemophilia  Avoidance of injury, prevention of bleeding.  Replacement with recombinant clotting factors.

63. *Gastro-esophageal reflux Definition :- Backflow of gastric contents into the esophagus Cause : - 1-It results from weakness or incompetence of the cardiac sphincter 2-It may be caused by a hiatus hernia Manifestations :- 1-Burning sensation at gastric region ( heart burn )aggravated by alcohol ,caffeine ,smoking and lying down. 2-Esophagitis and esophageal ulceration 3-Dysphagia and poor nutrition 4-Chronic esophagitis and possibility of esophageal cancer. Complication:- It leads to irritation and inflammation  ulceration of lower end of esophagus by its acidic contents.

64. Treatment: - Medical treatment 1-Eating of small frequent meals 2-Sleeping with elevated head 3-Consumption of fluids with foods 4-Use of anti-acids or proton pump inhibitors to reduce gastric acidity Surgical treatment Surgical correction of the present hiatus hernia .

65. Peptic ulcers Definition:- It is mucosal loss of any part in G.I.T. Mucosal loss of gastric mucosa  called gastric ulcer. Causes :- 1-Infection with Helicobacter pylori (in 80-95% of cases) ,that damage the protective mechanisms of the G.I.T . 2-Stressful conditions 3-Damage of mucus secreting cells 4-Excessive acid production in the stomach (increase gastrin hormone  increase acid secretion )( Zollinger – Ellison syndrome ) 5-Chronic use of aspirins and NSAIDS Complications :- 1-Hemorrhage :- Hematemesis and melena . 2-Gastric perforation :- Leading to peritonitis. 3-Fibrosis : Obstruction of duodenum and hour glass deformity of the stomach . 4-Malignant transformation :- 1-2% of cases  gastric carcinoma

66. Manifestations of peptic ulcer disease :- 1-Attacks of remission and exacerbation 2-Pain is relieved by eating(doudenal ulcer) ,or by anti-acids( gastric ulcer) 3-G.I.T bleeding (hematemesis&melena) (20-25% of cases) 4-Perforation of ulcer  ↑ mortality rate 5-G.I.T obstruction (fibrosis) Treatment of peptic ulcer :- 1-Avoidance of alcohol ,smoking and NSAIDS 2-Antibiotic therapy for H.P 3-Anticholinergic and antiacids 4-H2 receptors antagonists (proton -bump inhibitors) 5-Mucosal protective measures 6-Resection of tumor in pancreas

67. Crohn`s disease :- Definition :- Chronic transmural (affecting all layers of terminal ileum and colon  terminal ileitis),non-caseating granulomatous inflammatory reaction , charact-erized by skip lesions. Etiology :- 1-Idiopathic 2-Auto-immune disease 3-Post- infection ,mediated by inflammatory cytokines Pathology :- -The disease is commonly found in certain populations as in Jews , U.S ,Western Europe and Scandinavia in 20-40 years,with intermittent attacks of remission and exacerbation . -The disease can affects any region of G.I.T,but it is commonly seen in distal ileum and colon at ileocecal valve. -It form a transmural granulomatous inflammation of the affected parts,with distinctive cobble stone appearance to the mucosa -Areas of inflammations are separated by non inflammed (skip) areas .

68. Manifestations : - 1-Anorexia ,nausea and vomiting 2-Fever 3-Bloody diarrhea. 4-Abdominal pain 5-Loss of weight from malabsorption 6-Fibrosis and intestinal obstruction 7-Abdominal fistula ,between colon and abdominal wall Treatment :- 1-Nutritional support and total parenteral nutrition in severe cases. 2-Anti-inflammatory drugs 3-Blocking the action of cytokines by drugs or antibodies.

69. Ulcerative colitis Definition :- Chronic ulcero-inflammatory diseases affects the distal colon (rectum and colon) and extends backward (back-wash ileitis) Etiology :- 1-Idiopathic 2-Genetic or immunologic disorders Pathology :- 1-The disease affects individuals between 10-30 years especially who has family history of the disease with attacks of remission and exacerbation 2-The disease is commonly found in mucosa with continuous fashion (no skip areas) . Manifestations:- 1-Fever & abdominal pain 2-Chronic bloody diarrhea. 3-Weight loss and anemia 4-The possibility of perforated intestine ,blood loss and cancer colon.

70. Treatment :- 1-Nutritional support 2-Surgical resection of the diseased part to reduce incidence of cancer 3-Anti-inflammatory drugs and salicylates to suppress inflammation. 4-Sulfasalazine drug (sulfa and aminosalicylate) 5-Nicotine exerts a protective effect in ulcerative colitis .

71. U.colitis Crohn`s disease Item 10-30 years at recto-segmoid  proximally Non granulom. Absent Mainly mucosal Common Common Common ,and pseudo-polyps (+++) (+++) 20-40 years Any part of GIT at ileo-cecal region Granulomatous inflamm. present Through the wall Rare Rare Rare,but transmural fissures (+) (+) Age of onset Location Inflammation Skip lesions Layers involved Bloody stool Malabsorption Ulcers Crypt abscesses Propensity for malignancy

72. Diverticular disease of colon Definition :- Multiple sac-like protrusions of the intestinal wall . Types :- a-True diverticula :- Involves all layers of the intestinal wall B-False diverticula :- Involves only the mucosa . Etiology :- 1-In elder patients with chronic constipation 2-In individuals who consume a low fiber diet (chronic constipation) 3-Any condition that increase intraluminal pressure (constipation ) with weakened wall especially at sites of penetration of nutrient arteries or due to congenital weakeness in bowel wall . Manifestations :- Treatment : - 1-Increased bulk of diet and its fiber content 2-Antibiotics for diverticulitis 1-Asymptomatic 2-Changes in bowel habits and flatulence 3-Infection (diverticulitis )  perforated intestine  peritonitis

73. Manifestations of alcohol cirrhosis :- 1-Hepatosplenomegaly :- enlarged sizes of liver and spleen . 2-Ascites :- Caused by portal hypertension and hypoalbuminemia 3-Portal hypertension :-Increased blood pressure in portal circulation 4-Hepatorenal syndrome :- renal failure caused by liver failure 5-Jaundice:- due to liver damage 6-Hepatic encephalopathy :- Caused by accumulation of ammonia and other toxins in circulation  by pass hepatic detoxication  can reach the brain  Neurological dysfunction . 7-Esophageal varices :- Ruptured ,distended veins at lower end of the esophagus  hematemesis . Distended abdominal veins around umbilicus is called  caput medusa and in rectum  Piles 8-Reduced metabolism of sex hormones :- Hyperestrogenemia  gynecomastia in male,menstrual irregularities in females and abnormal sexual function of both ( loss of libido ) 9-Liver failure

74. 8-Reduced metabolism of sex hormones :- Hyperestrogenemia  gynecomastia in male,menstrual irregularities in females and abnormal sexual function of both ( loss of libido ) 9-Liver failure

75. Portal hypertension Definition :- Elevated blood pressure in portal circulation Causes : due to pre-hepatic ,hepatic and post – hepatic obstructive causes . Effects :- 1-The increased portal pressure causes stagnation of blood in spleen (splenomegaly) 2-The collateral blood vessels of the abdomen and esophagus are dilated forming varices. Symptoms :- 1-Bleeding of varices 2-Hepato-splenomegaly 3-Possibility of pancytopenia ( due to hypersplenism ) 4-Ascites due to portal hypertension and hypoalbuminemia Treatment of cirrhosis:-. 1-Nutritional supplementation with vitamins and reduction of protein diet to decrease ammonia 2-Diuretics to relieve fluid retention 3-Shunting operation to relieve bleeding from accessory collaterals 4-Management of symptoms of liver failure.

76. Gall stone formation (cholelithiasis) Bile composed of water,bile salts ,cholesterol and bilirubin -Gall stones are hardened precipitate of bile that predominantly contain cholesterol -Their sizes varies . - Contributors of gall stone formation -Gall stones may be detected by radiography ,ultrasonography and cholecystoscopy Manifestations of gall stones. 1-Nausea ,vomiting ,fever and chills . 2-Acute and severe biliary colic ( in small migratory stone) 3-A large sized stone  obstructs bile ducts  Jaundice . Treatment :- 1-Preventive measures;- low fat diet 2-Surgical treatment:-Cholecystectomy (surgically removed G.B.) 3-Endoscopic removal of the stone 4-Lithotripsy :- Breakdown of the stone by sound waves -Aging and sex (common in females) -Excess cholesterol or bilirubin -Obesity -Sudden dietary changes or abnormal fat metabolism .