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Revised By:

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 ofpacreaticductand acini acini secrete diagestive enzymes which are are:o Proteases(trypsinand chymotrypsin): Protein digestion

o Amylase: Carbohydrate digestion

o Lipase: Fat digestion

pancreatic lipase will diagest triglyceride to monoglyceride and free fatty acid. histoligicallyExocrine 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 ofislet of langerhansthat 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 cellsthat secrete glucagon

2- Beta cellsthat secrete insulin

3- deltacellsthat secrete somatostatin

4- Gcellsthat secrete gastrin

.

somatostatin

also called growth hormone inhibitor.

its secreted from two sites: delta cellsof pancreas and from hypothalamus.

somatostatin inhibit releasing of growth hormone from anterior pituitary.

gastrin causes stomach to produce acid(HCL)

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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 stimu-late 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 pancreasThere are three types of exocrine part diseases:

1- cystic fibrosis(fibrocystic disease) of pancreas

2- Pancreatitis(acute and chronic)

3- Tumors and tumor-like lesionof 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 glandsconcentration of electrolytes in eccrine glands Changes result from obstruction by viscid secretions

MucoviscidosisIt is viscid mucus secretion Obstruct pancreatic ducts, sweat gland, salivary gland ducts,

lungs, and bronchi.

Cystic Fibrosis Organs AffectedSalivary Glands

Obstruction of ductsDilatation

FibrosisGlandular atrophy

Sweat Glands

Hypersecretion of sodium chloridevaculation of eccrine gland cellsRespiratory Tract

Bronchitis, bronchiectasis, bronchiolitis, pneumonia, nasal polypsLiver

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 beobstruction of ductsthat will result inrupture, ruptureof duct will

lead torelease pancreatic enzyme into surround tissueresulting inautodigestionto pancreas and

surrounding (hemorrhage).

This obstruction of pancreatic duct resulting fromstone, tumor, ormetaplasiaof pancreatic lining.

Releasing of lipase in pancreas will causeEnzymatic fat necrosis(peripancreatic and omental fat

necrosis)

Released fatty acids combine with calcium to giveInsoluble 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 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)

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 shocko Infection

o Acute renal failure

o DIC "disseminated intravascular coagulopathy

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.

causing 80% of acute pancreatitis

The type of calcification in acute pancreatitis is dystrophic calcification

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.

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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. diabetesand 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...

Microscopic appearance of chronic pancreatitis

Ducts:o Fibrosis of wall lead to

o Luminal protein plugs or stones lead to Obstructiono 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

pseudocysts is somthing like cyste but without lining.

pseudocysts is part of pancreas have been swelling and out-pouched with empty lumen.

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.

Predisposing Factors of pancreatic cancer:

Smoking

Diet ( calories & protein) Chemicals (-naphthylamine, benzidine, nitrosamines)

Diabetes Mellitus

Hereditary Chronic Pancreatitis

Gallbladder disease

ductal adenocarcinoma

two types:1- serous "serous cystadenocarcinoma "(arising from acini)

2- mucinous"mucinous cystadenocarcinoma" (arise from pancreatic duct itself that havemucin 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"

microscopic appearance of ductal adenocarcinoma

irregular glands with malignant criteria (Invasive disordered malignant glands) Large ,polymorphic& hyperchromatic nuclei , prominent nuclei , mitosis Usually poorly differentiated

Pancreatic cancer most commonly arise from the head of pancreas which is close to am-

pulla 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).

Pancreatic cancer is mostly adenocarcinoma (ductal adenocarcinoma)

Trausseau's sign (Migratory Thrombophlebitis):Cancer head of pancreas until prove the otherwise

can happen with any tumor but more common in pancreatic carcinoma

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Islet Cell Neoplasms

They are either benign (adenoma) or malignant (carcinoma).

Insulinomao arise from cellso cause Insulin ... and so will cause hypoglycemiao mostly benign , only 5-10% malignant

Glucagonoma(cells) Glucagon Gastrinoma(G cells) ..Gastrin Somatostatinoma(delta cells) Somatostatin

Grossly

sharply circumscribed tumor mass with Smooth homogeneous surface.(unlike adenocarcinoma of the head which is hard infiltrated mass)

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 Glucagonoma Somatostatinoma Gastrinoma

Hypoglycemia Mild diabetes mellitus Diabetes mellitus Gastric hyperacidity

Mental confusion Anemia Steatorrhea Peptic ulceration

Loss of consciousness Necrotizing skin erythema Hypochlohydria

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 pancreas2- gastric hyperacidity3- scattered ulcers in duodenum and stomach

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.

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.

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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, 5thto 6thdecades- 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 Arthritiso Liver (enlargement, cirrhosis(100%), cancer, liver failure)

o Pancreas (possibly causing diabetes75-80%)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 gran-

ules Inflammation characteristically absent Demonstrated by iron stains (Prussian blue = Berlin blue)

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primary DM

1\ Type I DM also calledJuvenile orinsulin dependent DM. 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 sustibilityo enviromental(viruses or chemicals)

Islets Changes in type I:

1- decrease in number and size of islets2- decrease cell degranulation and depletion of insulin secretory stores.

3- Insulitis: Lymphocytic infiltration & edema of islets

4- Fibrosis

2\Type II DM usuallly seen inoverweightpatient 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.

pathogenesis:o Relative insufficiency of insulin relative to glucose load .. And / or

o Inability of peripheral tissues to respond to insulin (insulin resistance)

Islets Changes in type II:o Only Amyloid deposition

clincal features of type II DM:o thirst (polydepsia)

o polyuriao nocturia

o blurring of vision

o weight losso malaiseo liable to recurrent infection (recurrent skin, gum, and bladder infection)

o dry itchy skin

o peripheral neuritiso loss of sensation in feet & numbness (tingling) feet

Type I Patient depends on insulin for survival

Risk factors of type II DM arehereditaryandoverweight.

some said: insulin resistance is due to decrease in number of insulin receptors.

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)

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Complications of DiabetesIntroduction:(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 maylead to rupture, aneurysm, or atherosclerosis. this lesion called diabetic microangiopathy.

if injury affect intima of large vessels, it will called diabetic macroangiopathy.

1\DM complication on CVSa- Atherosclerosis (as result of intima injury)

b- secondary Hypertension

c- Myocardial infarction (ischemic heart disease)

d- Gangrene of limbs (as result from ischemia, commonly seen as dibeteic foot)

.

.

2\DM complication on CNSa- Cerebral Hemorrhage

b- Infarctionc- Coma (due to Ketoacidosis)

d- Peripheral Neuritis (neuropathy)

Diabetic microangiopathy is the pathogenesis or mechanism of DM complications.

usually we till patient with DM, dont cut the whole nail, because they might cause to them-

selves 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.

CNS complications is mainly due to vascular insufficiency.

Commonly DM cause diabetic tripathy

(MCQ)

diabetic tripathy consist:

1- diabetic nephropathy2- diabetic neuropathy3- 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 occulara- Diabetic Retinopathy (most important one)

b- Glaucoma( increase ocular pressure)c- Cataract

4\DM complication on RSthey result as result of lowering of patient resistance to infections. These complications are:

a- Bronchitis and Bronchopneumonia

b- Lung Abscess and Gangrenec- Pulmonary TB (in form of military TB or cavitary TB)

5\DM complication on kidneya- Glomerulosclerosis which will cause Nephrotic Syndrome, which include

o heavy Proteinuria

o Hypoalbuminemia

o generlized Edema

b- Pyelonephritisc- Necrosis of Renal Papillaed- Renal arteriolosclerosis (renal hypertension)

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

Cataract is Opacification of lens (Progressive increase in insoluble proteins).

it occur with normal old a e eo le.

in diabetic retinopathy there is

1hemorrhage 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 detachmentthat might lead to

blindness.

3-neovascularization : new blood vessel formationrapturehemorrhage.

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.

cavitary TB of lung usually affect the apex

all these complication (a,b,c,and d) can lead to chronic renal failure.

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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 andglomerular capsule (hyaline cap) or Bowmans capsule (capsular drop).

there is thickening of basement membrane.

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

thickening of basement membrane seen by using Massons trichrome stain.

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

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

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 amyloiddeposition in islet of pancreas

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)