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Introduction:
pancreas present in abdominal cavity. the head of pancreas is located in concavity of duodenum, its related to second part of duodenum. pancreas long 15 cm and wight 100 grams. pancreas consist of: head, neck, body, and tail. in the center of pancreas, there is pancreatic duct which lined by glandular epithelium. pancreatic duct will join common bile duct, and then will open in second part of duodenum by ampulla of Vater. pancreas have two component: 1- exocrine 2- endocrine

exocrine part
Exocrine part is consist of pacreatic duct and acini acini secrete diagestive enzymes which are are: o Proteases (trypsin and chymotrypsin): Protein digestion o Amylase: Carbohydrate digestion o Lipase: Fat digestion pancreatic lipase will diagest triglyceride to monoglyceride and free fatty acid. histoligically Exocrine part is divided into rhomboid lobules composed of acini Separated by thin fibrous septa containing blood vessels, nerves, and ducts

Endocrine part
endocrine part consist of islet of langerhans that secrete hormones. islet of langerhans is collection of cells in periphery of pancreatic duct. islet of langerhans consist of four types of cells: 1- Alpha cells that secrete glucagon 2- Beta cells that secrete insulin 3- delta cells that secrete somatostatin 4- G cells that secrete gastrin gastrin causes stomach to produce acid(HCL)

somatostatin also called growth hormone inhibitor. its secreted from two sites: delta cells of pancreas and from hypothalamus. somatostatin inhibit releasing of growth hormone from anterior pituitary. .
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alpha & beta cells

they have role in regulation of blood sugar (glucose) when blood contain high blood sugar (hyperglycemia) normally pancreas will secrete insulin (from beta cells) which will increase cellular uptake to glucose (especially fat cells uptake) .... result in reducing blood glucose and so achieving normal glucose level. in case of low blood sugar (hypoglycemia), pancreas will release glucagon that will stimulate liver to convert glycogen to glucose (glycogenolysis) ... increase blood glucose and so achieve normal glucose level. There is reciprocal mechanism between insulin & glucagon

Diseases of exocrine portion of pancreas

There are three types of exocrine part diseases: 1- cystic fibrosis (fibrocystic disease) of pancreas 2- Pancreatitis (acute and chronic) 3- Tumors and tumor-like lesion of pancreatic duct and acini 1-

cystic fibrosis (fibrocystic disease) of pancreas

commenst disease of this type is Mucoviscidosis. Hereditary Autosomal recessive Homozygous defect in chromosome 17 Viscid secretions in exocrine glands concentration of electrolytes in eccrine glands Changes result from obstruction by viscid secretions

Mucoviscidosis It is viscid mucus secretion Obstruct pancreatic ducts, sweat gland, salivary gland ducts, lungs, and bronchi.

Cystic Fibrosis Organs Affected

Salivary Glands Obstruction of ducts Dilatation Fibrosis Glandular atrophy Sweat Glands Hypersecretion of sodium chloride vaculation of eccrine gland cells Respiratory Tract Bronchitis, bronchiectasis, bronchiolitis, pneumonia, nasal polyps Liver Bile canaliculi plugged by viscid mucous, diffuse fatty change, portal fibrosis, ductal proliferation Pancreas Gross cysts, fatty replacement, maintained lobular architecture, interlobular fibrosis

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pancreatitis

(v.common)

1\acute pancreatitis
it is fetal disease.. patient will present with sever acute abdominal pain. Pathogenesis: in acute pancreatitis there will be obstruction of ducts that will result in rupture, rupture of duct will lead to release pancreatic enzyme into surround tissue resulting in autodigestion to pancreas and surrounding (hemorrhage). This obstruction of pancreatic duct resulting from stone, tumor, or metaplasia of pancreatic lining. Releasing of lipase in pancreas will cause Enzymatic fat necrosis (peripancreatic and omental fat necrosis) Released fatty acids combine with calcium to give Insoluble calcium soaps (whitish-yellow calcification) diagnosis: - serum amylase in first 24 hours. - serum lipase after 3-4 days (more specific).

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causes of acute pancreatitis: Alcoholism Cholelithiasis

causing 80% of acute pancreatitis

Trauma Ischemia Shock Extension of inflammation from adjacent tissues Blood-borne bacterial infections and viral infections Drugs (thiazides, sulfonamides, oral contraceptives) Hypothermia Hyperlipoproteinemia Hypercalcemia due to hyperparathyroidism

Acute pancreatitis grossly

pancreas is swollen and edematous. black-red hemorrhagic necrosis. Chalky whitish-yellow nodules of fat necrosis (calcification on top of fat necrosis) The type of calcification in acute pancreatitis is dystrophic calcification Peritoneal cavity typically contains blood-stained ascitic fluid White flecks of fat necrosis can involve omentum. mesentry & peripancreatic tissue

Microscopic appearance of acute pancreatitis

neutrophilic infiltration area of fat necrosis area of dark-blue calcification Necrosis of pancreatic lobules and ducts Necrosis of arteries with areas of hemorrhage

Death in acute pancreatitis

High mortality (20-30%) Cause of death: o Hypotensive shock o Infection o Acute renal failure o DIC "disseminated intravascular coagulopathy in DIC, patient will have hypofibrinogenemia resulting from consumption of fibrinogen in thrombosis formation. Any sever infection is liable to cause septicemia followed by DIC.

Acute Hemorrhagic Pancreatitis Acute Pancreatic Necrosis

Severe form of acute pancreatitis Characterized by Acute inflammation with fat necrosis and massive hemorrhage in and around the pancreas.

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2\Chronic Relapsing Pancreatitis

resulting from Repeated mild and subclinical pancreatitis. Pathogenesis there will be progressive destruction of pancreas (every time the attack of mild pancreatitis will cause damage to small part of pancreas, until (after years) destructed area of pancreas become large and patient will suffer from manifestion of loss of pancreatic enzymes and hormones (ex. diabetes and steatorrhea) patient present with Weight loss and Jaundice Etiology: o alcohol consumption o Common bile duct stones or stenosis o Familial hereditary pancreatitis (uncommon)

Gross appearance of chronic pancreatitis fibrosis (pancreas become fibrotic and hard) pancreatic duct dilated and filled with whitish calcified secretions Pancreas enlarged in early-stages (but in end-stage become shrunk), firm and nodular Cut surface smooth gray (loss of lobulations) Foci of calcification Tiny concretions or larger stones (frequent) Pseudocysts may be seen ... MCQ... pseudocysts is somthing like cyste but without lining. pseudocysts is part of pancreas have been swelling and out-pouched with empty lumen.

Microscopic appearance of chronic pancreatitis Ducts: o Fibrosis of wall lead to o Luminal protein plugs or stones lead to Obstruction o Squamous metaplasia o Mild dilatation of some inter and intra-lobular ducts o Residual duct Acini: o Atrophic with increase in interlobular fibrous tissue Chronic inflammatory infiltrate around lobules and ducts Islet tissue (involved in late stages only) o beta cells more affected and will result in DM

Loss of islets = Diabetes Loss of acini = Steatorrhea fat in stools)

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Pancreatic Carcinoma
"From exocrine portion" Frequency: most common in Head, then Body, and then Tail. Pancreatic cancer most commonly arise from the head of pancreas which is close to ampulla of Vatet, so cancer in it will obstruct ampulla and so will cause obstructive jaundice. Manifestation of pancreatic cancer in the head is early, but in the tail is so so late (appear after metastasis). Predisposing Factors of pancreatic cancer: Smoking Diet ( calories & protein) Chemicals (-naphthylamine, benzidine, nitrosamines) Diabetes Mellitus Hereditary Chronic Pancreatitis Gallbladder disease Pancreatic cancer is mostly adenocarcinoma (ductal adenocarcinoma) ductal adenocarcinoma two types: 1- serous "serous cystadenocarcinoma " (arising from acini) 2- mucinous " mucinous cystadenocarcinoma" (arise from pancreatic duct itself that have mucin secreting cells) pancreatic cancer of the head Head is the commonest site for pancreatic cancer.(70%) it is Hard fixed mass with poorly defined (irregular) infiltrative margin early Extension to ampulla and common bile duct leading to obstructive jaundice, and so early detectable. Body and tail pancreatic cancer characterize by silent growth and early metastasis (especially to liver and spleen) patient are at high risk of Multiple Migratory thrombosis in superficial and deep veins of the lower limb(Trausseau's sign) "MCQ" Trausseau's sign (Migratory Thrombophlebitis): Cancer head of pancreas until prove the otherwise can happen with any tumor but more common in pancreatic carcinoma microscopic appearance of ductal adenocarcinoma irregular glands with malignant criteria (Invasive disordered malignant glands) Large ,polymorphic& hyperchromatic nuclei , prominent nuclei , mitosis Usually poorly differentiated

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Islet Cell Neoplasms

They are either benign (adenoma) or malignant (carcinoma). Insulinoma o arise from cells o cause Insulin ... and so will cause hypoglycemia o mostly benign , only 5-10% malignant Glucagonoma ( cells) Glucagon Gastrinoma (G cells) .. Gastrin Somatostatinoma (delta cells) Somatostatin

60-90 malignant

grossly or microscopically we cant differentiate between Insulinoma, Glucagonoma, Gastrinoma, and Somatostatinoma, to differentiated between them we need measure level of hormone in blood. Grossly sharply circumscribed tumor mass with Smooth homogeneous surface. (unlike adenocarcinoma of the head which is hard infiltrated mass) We cant differentiate between malignant and benign tumors of islet cells by morphology. i.e. Behavior is not predicted by morphology unless there is metastasis. usually islet cell tumor that is < 2 cm tend to behave in a benign fashion. islet cell adenoma it is encapsulated mass contain Nests of homogenous endocrine cells (similar to normal glands) with Round uniform nuclei and granular eosinophilic cytoplasm separated by ductal cells.

Insulinoma Hypoglycemia Mental confusion Loss of consciousness

Glucagonoma Mild diabetes mellitus Anemia Necrotizing skin erythema

Somatostatinoma Diabetes mellitus Steatorrhea Hypochlohydria

Gastrinoma Gastric hyperacidity Peptic ulceration

somatostatinoma its hormonal effect is low because the hormone also secreted by thalamus. its effect mainly due to pressure that will applied on the surrounding leading to destruction of beta cells, alpha cells, and G cells. the effect will appear as DM due to destruction of beta cells. gastrinoma it will give us Zollinger-Ellison Syndrome Zollinger-Ellison Syndrome component ...MCQ...: 1- gastrinoma in pancreas 2- gastric hyperacidity 3- scattered ulcers in duodenum and stomach
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Diabetes Mellitus (DM)

DM is Metabolic disorders of glucose utilization, Characterized by: hyperglycemia and glycosurea. islet of langerhans & blood sugar normally, high blood sugar promote insulin release from pancreas, insulin will stimulate formation of glycogen in liver and glucose uptake so reduce blood sugar to normal level. normally, low blood sugar stimulate pancreas to release glucagon, glucagon stimulate glycogenolysis in liver (breaking down glycogen) so glucose will reproduced and release to blood .. so blood sugar will elevated to normal level. Types of DM 1- primary DM a- Type I ((Juvenile, insulin dependent, treated by insulin) 10-20% b- type II (Adult, non-insulin dependent, treated by oral hypoglycemic) 80-90% Type II patient will take insulin drug, only in case of stress, infection, or surgery. 2- secondary DM a- Chronic pancreatitis b- Pancreatectomy c- Hormone-producing tumors (that produce anti-insulin action hormones) o especially pituitary adenoma (acromegaly, increase secretion of growth hormone) o glucagonoma o tumor causing hyperthyroidism o Caushing syndrome, which release cortisol(steroid) d- Drugs (corticosteroids) e- Hemochromatosis

Iron Metabolism
1-2 mg of iron enters and leaves the body every day Hemochromatosis: Excessive accumulation in parenchymal cells, especially liver & pancreas The body has no mechanism to clear excess iron

Normal deposition of iron in cells (due to hemolysis) called hemosiderosis.

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Iron Storage Abnormalities:

Secondary hemochromatosis hemosiderosis (Overload)
- Hemolytic anemia - Repeated blood transfusions - intake

Primary hereditary hemochromatosis (autosomal recessive)

- Defect in regulation of intestinal absorption of dietary iron - Males, 5th to 6th decades - iron is stored in tissues, specifically liver, heart, pancreas, skin, joints (bronzed diabetes) Hemochromatosis genetically determined disease characterized by increase iron absorption. iron absorption occur in terminal ileum. iron will be stored in tissues (espically in liver, heart, and pancreas) manifestation of Hemochromatosis: (essay) o Arthritis o Liver (enlargement, cirrhosis(100%), cancer, liver failure) o Pancreas (possibly causing diabetes 75-80%) o Heart (arrhythmia or congestive heart failure) o Abnormal skin pigmentation )75-80% (gray or bronze), and so it called bronzed diabetes. o Thyroid deficiency/adrenal glands damage Slightly enlarged chocolate colored , later: micronodular cirrhotic pigmented liver Iron in Kupffer cells, hepatocytes, biliary epithelium as golden yellow hemosiderin granules Inflammation characteristically absent Demonstrated by iron stains (Prussian blue = Berlin blue)
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primary DM
1\ Type I DM
also called Juvenile or insulin dependent DM. Type I Patient depends on insulin for survival usually affect young people less than 20 y. patient usually have normal weight. Pathogenesis: insulin producing cells are destroyed and so sever lack of insulin. so there is decrease in beta-cells mass due to: o autoimmune (there is anti-insulin antibodies that will attack and damge beta-cells). o genetic sustibility o enviromental (viruses or chemicals)

Islets Changes in type I: 1- decrease in number and size of islets 2- decrease cell degranulation and depletion of insulin secretory stores. 3- Insulitis: Lymphocytic infiltration & edema of islets 4- Fibrosis

2\Type II DM
usuallly seen in overweight patient that are older than 30 y. there is hereditary factor so if parents have type II DM usually their son will get diabetes in adulthood.

Risk factors of type II DM are hereditary and overweight. pathogenesis: o Relative insufficiency of insulin relative to glucose load .. And / or o Inability of peripheral tissues to respond to insulin (insulin resistance) some said: insulin resistance is due to decrease in number of insulin receptors. Islets Changes in type II: o Only Amyloid deposition

amyloid is waxy substance deposited in wall of blood vessels, interstitial tissue of different organs. amyloid deposition result from antibody-antigen reaction, is either primary (with unknown cause) or secondary ( commonly seen in chronic disease such as TB, type II DM, malignant tumors, and chronic suppurative lung disease like bronchoectasis and lung abscess) clincal features of type II DM: o thirst (polydepsia) o polyuria o nocturia o blurring of vision o weight loss o malaise o liable to recurrent infection (recurrent skin, gum, and bladder infection) o dry itchy skin o peripheral neuritis o loss of sensation in feet & numbness (tingling) feet

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Complications of Diabetes
Introduction:(imp.) mostly all complication of diabetes is as result of increase glucose blood level. blood vessels (especially small vessels) are the most tissue influenced by increase glucose level. high glucose level will cause irritation and injury to intima of small blood vessel, which may lead to rupture, aneurysm, or atherosclerosis. this lesion called diabetic microangiopathy. if injury affect intima of large vessels, it will called diabetic macroangiopathy. Diabetic microangiopathy is the pathogenesis or mechanism of DM complications.

1\DM complication on CVS

abcdAtherosclerosis (as result of intima injury) secondary Hypertension Myocardial infarction (ischemic heart disease) Gangrene of limbs (as result from ischemia, commonly seen as dibeteic foot) usually we till patient with DM, dont cut the whole nail, because they might cause to themselves lesion (injury), if injury happen, they will get gangrene due to decrease their resistance and ischemia with presence of bacterial putrefaction. . usually gangrene start in big toe, and if it sever will extend to all foot, and if it more sever it will extend up to leg. Gangrene is treated by amputation of big toe, foot, or lower knee amputation according to its extending. .

2\DM complication on CNS CNS complications is mainly due to vascular insufficiency.

abcdCerebral Hemorrhage Infarction Coma (due to Ketoacidosis) Peripheral Neuritis (neuropathy) Commonly DM cause diabetic tripathy (MCQ) diabetic tripathy consist: 1- diabetic nephropathy 2- diabetic neuropathy 3- diabetic retinopathy

Diabetic ketoacidosis ~for understanding~ if there is insufficient insulin,1) muscle cells will release amino acid, 2) fatty cells will release glycerol and fatty acid, 3) increase in glucagon. Amino acid and glycerol will go to liver and converted there to glucose. also glycogen chain of liver will converted to glucose due to increased glucagon (glycogenolysis). fatty acids will go to liver and will be converted there to ketoacids (ketogensis). so glucose and ketoacids will be increased in blood. increase ketoacids in blood will decrease the Ph (acidic blood), acidic blood is toxic, and this condition called diabetic ketoacidosis. diabetic ketoacidosis happen in uncontrolled DM.

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3\DM complication on occular

a- Diabetic Retinopathy (most important one) b- Glaucoma( increase ocular pressure) c- Cataract Cataract is Opacification of lens (Progressive increase in insoluble proteins). it occur with normal old age people. in diabetic retinopathy there is 1 hemorrhage in retina 2- microaneurysm of retinal blood vessels, it liable to rapture causing hemorrhage, with time this hemorrhage will heal by fibrosis. this fibrosis will cause multiple retinal detachment that might lead to blindness. 3- neovascularization : new blood vessel formation rapture hemorrhage. Diabetic patient should regularly visit ophthalmologist for retinal check-up. if patient have diabetic retinopathy, this mean diabetes is uncontrolled. Patient with diabetic retinopathy (even after treatment) will have decreased visual acuity.

4\DM complication on RS
they result as result of lowering of patient resistance to infections. These complications are: a- Bronchitis and Bronchopneumonia b- Lung Abscess and Gangrene c- Pulmonary TB (in form of military TB or cavitary TB) cavitary TB of lung usually affect the apex

5\DM complication on kidney

a- Glomerulosclerosis which will cause Nephrotic Syndrome, which include o heavy Proteinuria o Hypoalbuminemia o generlized Edema b- Pyelonephritis c- Necrosis of Renal Papillae d- Renal arteriolosclerosis (renal hypertension) all these complication (a,b,c,and d) can lead to chronic renal failure.

Diabetic Glomerulosclerosis there is three types: 1- nodular (Kimmelsteil-Wilson Lesion) this lesion is the only specific lesion for diabetes . present in 10-35% of diabetic Glomerulosclerosis Nodular deposits of matrix within mesangial core in periphery of Glomerulos. there is Obliteration to capillary lumen

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2- difused affect whole glomerulus characterized by Linear hyalinized thickening of basement membrane and Diffuse mesangial matrix + mesangial cell proliferation thickening of basement membrane will affect capillaries loop , bowman capsule, and membranes of tubules and vessels. there will be decrease in number of podocytes. 3- Exudative characterized by Hyaline deposits with eosinophilic material in capillary lumen and glomerular capsule (hyaline cap) or Bowmans capsule (capsular drop). there is thickening of basement membrane. thickening of basement membrane seen by using Massons trichrome stain.

6\DM complication on skin

with DM there is increase liability to Infection especially in area of Friction with cloths, especially in the back of neck.. infection of skin present as Carbuncle/Cellulitis Carbuncle is localized suppurative inflammation similar to abscess but is larger and contain multiple cavities that open to skin by multiple sinuses discharging pus.

Stress of infection\surgery increase insulin requirement, so patient with type I DM will increase dose, and patient with type II DM will take insulin temporarily with oral hypoglycemic.

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Q1/ Pseudocysts common seen in: a- pancreatic stone b- chronic pancreatitis c- gall bladder stone d- acute cholecystitis

Q2/alpha cell tumor : a- cause gastric hyperacidity b- associated with Zollinger-Ellison Syndrome. c- associated with increase serum insulin level d- cause hyperglycemia

Q3/according to primary DM which is correct : a- type II is insulin dependent and affect adult b- with type II, there is fibrosis in islet of pancreas c- type I is insulin dependent and affect children d- with type I, there is amyloid deposition in islet of pancreas

Q4/according to islet tumors which is correct : a- insulinoma mostly malignant b- gastrinoma cause decrease serum gastrin. c- somatostatinoma have great pathological hormonal effect d- glucagonoma cause mild DM

Q5/commonest site of pancreatic cancer is : a- head b- body c- tail d- neck

Q6/beta cell tumors : a- cause increase in gastrin level b- cause hyperglycemia c- cause hypoglycemia d- cause Zollinger-Ellison Syndrome

Key answer: 1 (b), 2 (d), 3 (c), 4(d), 5(a), 6 (c) 14 | P a g e