L441) Enumerate the functions of hepato-biliary system: - liver: Synthetic function = 5 things. Metabolic functions = 7Bile secretion 2Detoxicating and protective functionMiscellaneous function-gallbladder: Storage and concentration of bile Control of flow of bile following a mealReduces alkalinity of the stored bile- pH decreases from 8.6 to 7.4Regulates equalization of pressure in biliary systemSecretes mucin (mucus) which makes bile thick (viscous)-Bile: bile salts helps in digestion and absorption of fatsNeutralization of acid chyme from the stomachExcretion- it removes many drug, pigments and various inorganic substances like copper , zinc , mercurySolubility of cholesterol-cholesterol micelle in bile allows transport of cholesterol

2) discuss composition bilebile salts, water, bilirubin, cholesterol, fatty acids, lecithin, Na, K, ca, CL (ALKALINE PHOSPTASE)

3) mechanism of bile secretiontwo stages: secretion by hepatocytessecretion by bile duct

4) explain factors affecting flow of bile nervous regulation hormonal : secretin and CCK cholerctic substancescholagogues substances

5) role of enterohepatic circulation of bile The quantity of bile secreted by liver each day is highly dependent on availability of bile salts. The greater the quantityof bile salts in the enterohepatic circulation(about 2.5 g), the greater the rate of bile secretion.

biochemistryL41

1) formation of fatty acid from stored triacylglycerol

trigacylglycerol ===> di,monoglyecerol ===> will give glycerol + fatty acids

*by hormone sensitve lipase

*glycerol cant be metoblized by adipose tissues, go to liver, converted to glycerol phosphate for: #TAG synthesis #converted to dihydroxyacetone phosphate. for glycolysis & gluconeogensis

*fatty acid bound to albumin except RBC , brain cells (cant use FA)

2) beta oxidation process in mitochondria produce: acetyl coA, NADH, FADH2

1) in cytoplasm, fatty acid ===> acyl coA by acyl synthase. 2) transport to mitochondria, by carnitine shuttle (rate limiting transport) acyl coA ==> carnitine ==> acyl Cantonby outer membrane: carnitine acyl coA Transfarese I acyl carnitine ==> carnitine ==> acyl coA by Inner membrane: carnitine acyl coA Transfarese II 3) beta oxidation happens in 4 steps 1) oxidation 2) hydration3) oxidation 4) cleavage

3) stoichiometry of beta oxidation of fatty acids

palmitic acid 16C = 7 rounds, 7 NADH, 7 FADH, 8 Acetyl coA 7X3 = 217X2 = 148X12 =96

= 131 , ATP used= 2 so net production is 129

* note : very long chain fatty acids oxidized in peroxisomes * alpha oxidation when there is methyl group at beta carbon * phytanic acid is 20 carbon = 19 pristinic acid by alpha oxidation. * omega oxidation is in endoplasmic reticulum, important when medium chain acyl dehydrogenase

deficiency * carnitine deficinecy = go back to slides.

L461-Describe process of ketone body formation in liverKetogenesis is the process by which ketone bodies are produced as a result of fatty acid breakdown.in liver, mitochondrial matrix.Acetyl CoA is the precursorketone bodies are: 1) acetoacetate 2) Acetone 3) 3-OH butyrate (doesnt posses a keto group)

2) Describe the process of ketone body utilization in peripheral tissues RBC cant utilize ketones.occur when starvation (lack of glucose) and diabetes mellitus Thiophorase is absent in liver, can’t utilize it.

3) understand the importance of diverting acetyl coA for ketogensisThis causes an overproduction production of Acetyl coA which cannot be fully handled by citric acid cycle.Furthermore, the TCA cycle is impaired due to deficiency of oxaloacetate, (diverted to gluconeogenesis)The result is accumulation of acetyl coA and its diversion to overproduction of KB.

4) Regulation of Ketogenesis

Promoters of Ketogenesis : Glucagon, Fatty acids, Ketogenic Amino acids – Leucine, Lysine

Inhibitors of Ketogenesis: Insulin, Glucose, Glycerol, Glucogenic amino acids – Glycine, Alanine, Serine. etc

L461- reactions synthesise tyrosine from phenylalanineglucogenic and partly ketogenic.Phenylalanine is essential and Tyrosine is non-essential

it needs o2, and 2 H To form H2O it will get 2H from H4 Biopterin. NADPH+H is needed to get H2 Bioterin to H4 Again.

thiophrase

2- catabolism of Tyrosine

3- Special product formed from phenylalanine and Tyrosine* Melanin – Skin Pigment. * Catecholamines – Dopamine, Nor-Adrenaline (Nor-Epinephrine) andAdrenaline (Epinephrine)*thyroxine – Thyroid Hormone.( look at the reactions if you have time :)4- metabolic defectsThere are 5 types of PKU:Type I – Deficiency of Phenylalanine hydroxylase.Type II & III – Deficiency of Dihydrobiopterine reductase.Type IV & V – Deficiency of Tetrahydrobiopterine.Guthrie Test, Ferric Chloride test, DNA Probes

PKU

Tyrosinemia II

alkaptounria

Tyrosinemia III

Tyrosinemia I

L57 -compounds with large negative Eo are strong reducing agents. positive= oxidizing NAD, NADH - FAD, FADH = REDUCING AGENTS O2, H2O, CYTOCHROME B Fe3, Fe2= oxidizing

1) what are the co enzymes derived from vitamins B1,B2,B3 and what is their role in redox actions?

# B1 = TPP = thiamine pyrophosphate : (metabolism of carbohydrates)1- oxidative decarboxylation of pyruvate to acetyl coA (PDH enzyme) 2- oxidative decarboxylation of alpha ketoglutarate to succinyl coA ( alpha ketoglutarate dehydrogenase enzyme) # B2 = FMN, FAD 1- NADH Dehydrogenase (FMN- FMNH2)2- Succinate dehydrogenase (FAD-FADH2)3- Glycerol phosphate dehydrogenase (FAD-FADH2) 4- Xanthine oxidase (FAD-FADH2) 5- L-amino acid oxidase (FMN-FMN2) # B3= NAD- NADP1- (PDH enzyme) NAD-NADH 2- alpha ketoglutarate dehydrogenase enzyme) 3- Lactate dehydrogenase 4- Malate dehydrogenase (Glucose 6 phosphodehydrognase (NADP) Not utilized in ETC

2) describe Respiratory chain complexes ● Complex - 1 – catalyzes electron transfer from NADH to ubiquinone. = 4 protons

(HYDROGEN) - FMN, Iron sulfur proteins as co enzymes, 2 electrons. ● Complex -11 – catalyzes electron transfer from succinate to ubiquinone = FAD+ Iron sulfur … ,

no protons. 2 electrons. ● Complex -111 – catalyzes electron transfer from ubiquinone to cytochrome c. , 4 protons ● Complex - 1v – catalyzes electron transfer from cytochrome c to O₂. , 2 protons● Complex - v –ATP synthase – ATP is synthesized from ADP.

inhibitors of electron transport are : retenone, antimycin A , cn or co .

L69 VITAMIN A: chemistry: poly isoprenoid compounds having a beta ionone ring system.

absorption vA: with fat and require bile saltIn Intestine beta carotene is cleaved by dioxygenase to form retinal.Retinal ! Retinol. In the mucosal cell, Retinol is re-esterified with fatty acid, incorporated into chylomicrons and transported to liver. In the liver vitamin A is stored as Retinol palmitate. transport: to peripheral tissues as trans retinol by the retinol binding protein (RBP).The retinol-RBP complex binds to specific receptors on the retina, skin, gonads and other tissues.Inside the cytoplasm of cells, vitamin binds to cellular retinoic acid binding protein (CRBP) and finally to hormone responsive elements of DNA. FUNCTION: 1. Retinal helps in vision ! Wald’s Visual cycle.2. Retinoic acid acts like steroid hormone and helps in regulation of gene expression and differentiation of tissues.3. Retinol is necessary for the reproductive system.4. Anti-oxidant property: Prevents Cancer, Heart attacks.5. Maintenance of normal epithelium and skin.

deficiency: 1. Night blindness 2. Xerophthalmia. 3. Bitot’s spots 4. Keratomalacia. 6. Skin and Mucous membrane lesions.

Toxicity: Anorexia, Irritability, Headache, Peeling of skin, Drowsiness and vomiting., Hypercarotenemia

VITAMIN Achemistry: The tocopherols are derivatives of 6-OH Chromane ring with isoprenoid side chain. 8 tocopherols , α tocopherol is the most active. antioxidant property = OH groupabsorption: with fat, bile salt is requiredtransport: in liver incorporated into lipoproteinstorage: liver, muscles and adipose tissueplasma level less than 1mg\dlFUNCTION: 1_preserves and maintains the germinal epithelium of gonads for proper reproduction functions2_Anti-sterility vitamin3_optimum absorption of aminoacids from the intestine.4_synthesis of nucleic acid5_protects liver from being damaged by toxic compounds6_essential for the membrane structure and integrity of the cell7_prevents the peroxidation of PUFA in various tissues and membranes.8_ protects RBC from hemolysis by oxidising agents9_most important: antioxidantDeficiency: Sterility, Degerative changes in muscle, Megaloblastic anemia, Neuropathy, Fragility of RBC – hemolytic anemia.

VITAMIN K chemistry: Naphthoquinone derivatives with long isoprenoid side chain.absorption: SAME ABOVE , stored in liver and can be synthesized by intestinal bacteria. function: 1) co enzyme for gamma carboxylase2) The proteins require vitamin k activity are: Clotting factors 11,v11,1x and x. , Bone remodelling proteins , Structural proteins of kidney, lung ,spleen.3) anticoagulants for treating the patients.toxicity: Hemolysis, Hyperbilirubinemia, Kernicterus, Brain damagedeficiency: Hemorrhagic disease of the new bornin adults: bruising, echymosis, mucus membrane bleeding, pos traumatic bleeding, internal bleeding.*

* L58: combined process of electron transport chain and ATP synthesis is called (oxidative phosphorylation)

* ATP synthase (complex v) has two domains: F0 , F1* F0 = integral membrane complex : has proton pore , sensitive to oligomycin * F1 = Peripheral = = : binding site of ATP & ADP * P:O ratio 3H+ For 1ATP produced , 1H+ for transport ADP&ATP&Pi = 4H+ Translocated for each

1ATP *

* Substrate level phosphorylation: (direct) * two reactions of substrate level phosphorylation in glcolysis and one in citric acid cycle: * 1.3-Bisphosphoglycerate ==> 3-Phosphoglycerate, By the enzyme Bisphospoglycerate kinase.* Phosphoenol Pyruvate ==> Pyruvate, By the enzyme Pyruvate kinase.* Succinyl coA ==> Succinate. By the enzyme Succinate thiokinase.

uncouplers • Oligomycin - binds to the stalk of ATP synthase, closing the Proton channel

– No re-entry of protons• Uncoupling Proteins:

– Physiologically present– Allow leak of protons

• UCP1 (thermogenin) – Brown Fat (90% of respiratory energy is wasted as heat)• UCP 2 and UCP3

– Synthetic uncouplers:• 2,4 dinitrophenol• High doses of Salicylates like aspirin

MICRO L70 PROTOZOAS;1)Entamoeba hisolytica = * affect large intestines, Protozoa, causes Amoebic dysentery two stages: cyst (INFECTIVE form) and trophozite, source is humans, feco-oral transmissionlab diagnosis: stool: trophozoites and ingested RBC also cysts, anchovy sauce pus in hepatic abscess.

2) Giardia lamblia = *protozoa, affect small intestines. causes Traveller’s diarrhoea infective stage is cyst outside the body. transmission is by uncholrinated water, oral anal sex. stools are greasy, watery, semisolid, bulky and foul smelling.

3) Cryptosporidium parvum, sources is animal or humans. causes watery diarrhoea in AIDS patients. modified ZN stain.

-1- Ascaris lumbricoides = SI, nematode, commonest, female is longer than male, produces oviparous then dies. ingestion of eggs ==> Larva hatch penetrate intestines note that eggs can live in soils for 1 month. + (Heart lung cycle)complications include: appendicitis, pancreatitis, acute biliary obstruction, pneumonitis, loffeler syndrome. treatment of choice is mebendazole.

2- Hook worms nematode, FILARIFORM LARVAE is infective form by skin penetration (walk without shoes) life cycle = egg in faces = mature in soil == develop to filariform == penetrate == go everywhere. it sucks blood with the aid of anticoagulant so anemia, itch skin (erythema, prutitis), loefeller pneumonia = mebendazole.

3- Strongyloids skin penetration by rhabditiform larvaeinternal autoreinfection

4- Taenia Saginata cestodes (tape), cause taeniasis, consumption of beef(life cycle)

5-tenia soluim pork, cysticerci is infective form, causes cysticerosis, neurocystecreosis, opthalmocystecrosis.

6- eneterobius vermicularis nematodes,cold climate,perianal itching , scotch test. 7- Fasciola hepatica in liver,

L72 rotavirus, non enveloped double standard RNAfeco oral route, cold temperaturepathogensis; ingestion infect epithelial cells of SI. shortening and atrophy of villi, decrease digestive enzyme production, malabsorption state.lab diagnosis; ELISA, PCR (most senstive), antibody to rotavirus IgM, IgG (M In acute), Electron microscopy. Calcivirus ss RNA, major cause of non bacterial epidemic gastroenteritisLAB; RTPCR, EM, ELISAHEPTITIS A,E; E CAN be transmitted by blood and vertical transmission املقارنة*candidia esophagitis AIDS indicator diseae. , white patches. see lab diagnosis.

l631)Identify normal flora of GIT: Duodenum, jejunum and upper ileum: Enterococci and lactobacilli Lower ileum, ceacum and large intestine: Fecal flora96-99% fecal flora are Anaerobes Bacteroides fragilis, Fusobacterium spp, Clostridium spp (C perferingens), Anaerobic lactobacilli, Anaerobic streptococci (Peptostreptococci) 1-4% are Coliform (e.g. E. coli, Klebsiella ), Enterococci, Pseudomonas

2) Explain the beneficial of microbial flora of GIT

– Competition for receptors or binding sites on host cells, – Competition for nutrients, – Mutual inhibition by metabolic or toxic products – The intestinal bacteria produce several B vitamins and vitamin K – Development & function of the mucosal immune system – Certain bacteria metabolize dietary carcinogens

3) Broad spectrum antibiotics associated with C. difficile infectionClindamycin, Flouroquinolones, second- and third-generation cephalosporins

*The C. difficile cause the disease known as “Pseudomembranous colitis” or “antibiotic associated diarrhea” complication of this disease is megacolon.

L76

Non typhoidal salmonella infections* animal food products and fresh food contaminated with animal waste* Mechanism: charactrized by massive neutrophil infiltration into both large and small bowel

mucosa, degranulation and release of toxic substances by neutrophils result in damage the mucosa causing inflammatory diarrhoea. 6-48 h after ingestion. self limited 3-7 days.

Vibrio Cholera (watery diarrhoea) * Exotoxin (cholera toxin) is produced. has two subunits, A,B* Mechanism: B Bind to Gm1 receptor, delivers A Inside the cell * A increases cyclic AMP * CAMP inhibits sodium transport system in villus cells + activates chloride secretion * accumulation of sodium, chloride in I lumen = water moves from cell to lumen by osmosis * 24-48 h , cloudy fluid with flecks of mucus, it has no bad door * Complications: 1) dehydration=> hypovolemic shock 2) renal failure Bacillary dysentery (shigella) * gram - bacilli . feco oral and can be transmitted in food (outbreaks), flies, RBC+WBS++* mechanism: by invasion to clonic epithelial cells => multiplication => spread to cells =>

inflammatory cells recruitment => destruction of mucosa * 1-4 days. tenesmusHemolytic uremic syndrome * caused by S. dysentrie type 1* mechanism: inhibits cell protein biosynthesis => cell death * ,mechanism of the disease: shiga toxin enters the circulation and binds to Gb3 receptors on

vascular endothelium. >toxin move into cell, inhibits cell protein biosynthesis => cell death* injury activates blood platelets and clot formation (thrombocytopenia), hemolysis , kidney failure. E.coli * enterotoxic: Enterotoxin like cholera toxin watery diarrhea ( TRAVELLER DIARRHEA)* enteropathgenic in young children (OUTBREAKS OF INFANTILE DIARRHEA)

* enterohemorrhgic cytotoxin like shiga toxin (hemolytic uremic s), verotoxin , unpasteurized milk (attach to epithelium (cytolysis) , hemorrhagic colitis

* enteroinvasive invasion, dysentry CAMPYLOBACTER* GNR. motile and curved* found in animal GI food, House pets .. don't cause it to host. * by invasion Staphylococcus food poisoning * enterotoxin. heat stable. 2-6h. dairy, meatBacillus * B. CEREUS, gram + spore produce rods not well cooked food. (under 100) 10-50 c =

germination * toxin : 1) emetic toxin(nausea + vomiting) 1-6 h 2) diarrheal toxin 8-16h L66* TYPES OF GIT INFECTIONS: 1) Endogenous: normal flora , predisposing factors (dental extraction, peritonitis by E.coli, high sugar intake, weak immunity)2) exogenous: contaminated food* LAB diagnosis of food poisoning : 1)gram staining 2) culture (s.aureus : mannitol salt agar &

hemolytic agar - what will u see?) cereus (egg yolk phenol red polymyxin agar MYPA) 3)rapid toxin detection 4)PCR

* NON inflammatory diarrhoea (cholera, enterotoxigenic E.coli)= in low socioeconomic countries and floods (water borne)

* LAB DIAGNOSIS for NID: stool examination, microscopy, culture (TCBS medium = v.cholera) (McConky agar=Ecoli), serology (ELISA) = ECOLI. (slide agglutination V.cholera)

* anaerobes usually by bacteroids fragilis = appendictis, peritonitis, hepatic and subphrenic abscess

* H.PYLORI : oral oral, feco oral. LAB: 1)endoscopic biopsy 2)culture 3)urease test 4)ELISA 5)urease breath test

ANATOMY L40 1-muscles of the posterior abdominal wall Quadratus lumborum = lumbar plexus. action: It fixes or depresses the 12th rib during respiration. lateral flexion of the vertebral column origin: iliolumbar ligament + the iliac crest+ the transverse processes of the lower lumbar vertebraeinsertion: lower border of the 12th rib+ transverse processes of the upper 4 lumbar vertebrae.

Psoas major = lumbar plexus. action: Flexion of the thigh at the hip joint.Flexion of the trunk on the thigh. origin: Transverse processes, bodies, & intervertebral discs of T12- L5insertion: With iliacus into lesser trochanter of femur Iliacus = Femoral nerve. origin: Iliac fossa

shigella campylobacter (inflammatory diarrhoea)

short incubation period & short illness long

only human to human animal to human

in children adults

gay bowel syndrome + survives Acidic pH seagull appearance , microaerophilic conditions

2- Aorta • Enters the abdomen : Aortic opening of the diaphragm in front of the T12.• Branches:• 3 anterior visceral branches : Celiac artery, Superior mesenteric artery, & Inferior mesenteric

artery• 3 lateral visceral branches: Suprarenal artery, Renal artery, & Testicular or Ovarian artery• 5 lateral abdominal wall branches: The inferior phrenic artery and four lumbar arteries• 3 terminal branches: the two common iliac arteries (L4) and the median sacral artery

3-Inferior vena cava• Formed by the union of the common iliac veins behind the right common iliac artery at the

level of the 5th lumbar vertebra . • Tributaries: • A. Anterior visceral tributaries: 2 Hepatic veins. B. Lateral visceral tributaries: 1. Right suprarenal vein 2. Right gonadal vein 3. Renal veins. C. Lateral abdominal wall tributaries: Inferior phrenic vein, 4 lumbar veins D. Veins of the origin: Two common iliac veins and the median sacral vein

4- lumbar plexus I Get Lemon On Fridays 2 from 1 origin : iliouinguinal, iliohypogastric (L1) 2 from 2 origin : Gentiofemoral (L1,2) . Lateral cutaneous nerve (L2,3) 2 from 3 origin : Obturator . Femoral nerve (L2,3,4)Anterior: G. Lateral: I, L,FMedial border: O

L43 1-Describe porta hepatisIs hilum (door) of the liver found on the posteroinferior surface and lies between the caudate and quadrate lobes.Structures in it:Right and left hepatic ducts.Right and left branches of hepatic artery.Portal vein.Sympathetic and parasympathetic nerve fibresA few hepatic lymph nodes.

2-Identify components of hepato-biliary systemRight and left hepatic ductsCommon hepatic duct (CHD)Cystic ductBile duct

3-Tributaries of the portal veinSplenic veinInferior mesenteric veinSuperior mesenteric veinLeft gastric veinRight gastric vein

Cystic veins

*portal vein Drains blood from Lower 3rd of esophagus to ½ of anal canal.Spleen, pancreas and gall bladder4-Porto-systemic anastomosis# normal conditions portal vein will drain into IVC by hepatic vein # smaller communications exist between the portal and systemic systems, and they become important when the direct route becomes blocked:

At the lower 3rd of esophagus Halfway down the anal canal The paraumbilical veins The veins of the ascending and descending colon, duodenum, pancreas and liver and liver (portal) anastomose with renal, lumbar and phrenic veins what is the anatomy of gallbladder?

pathology L49 ACUTE HEPTITIS: Gross Changes: Enlarged, reddened liver Microscopic changes: Hepatocyte injury: swelling (ballooning degeneration)•Cholestasis: bile plugs•HCV: mild fatty change of hepatocytes•Hepatocyte necrosis: Cytolysis (rupture) or apoptosis (shrinkage)

• If severe: bridging necrosis (portal-portal, central-central,• portal-central)• Lobular disarray: loss of normal architecture

•Regenerative changes: hepatocyte proliferation•Sinusoidal cell reactive changes•Accumulation of phagocytosed cellular debris in Kupffer cells•Influx of mononuclear cells into sinusoids•Portal tracts: Inflammation: predominantly mononuclear

• Inflammatory spillover into adjacent parenchyma, with hepatocyte• necrosis

Chronic: Hepatocyte injury, necrosis, apoptosis, and regenerationSinusoidal cell reactive changesPortal tracts: Inflammation. Confined to portal tracts, or Spillover into adjacent parenchyma Bridging inflammation and necrosisFibrosis: Portal deposition, or Portal and periportal deposition, or Formation of bridging fibrous septaHBV: ground-glass hepatocytes (accumulation of HBsAg)HCV: bile duct epithelial cell proliferation, lymphoid aggregateformation. (see pics)

The hallmark of chronic liver damage is the deposition of fibrous tissue.- portal fibrosis, linking of fibrous septa (bridging fibrosis

L51* The pathogenesis is attributed to T cell–mediated autoimmunity, in which hepatocyte injury is

caused by IFN-γ produced by CD4+ and CD8+ T cells* a female predominance* classified into types 1 and 2 * Type 1 is characterized by the presence of antinuclear (ANA), anti–smooth muscle (SMA), anti–

actin (AAA), and anti–soluble liver antigen/liver-pancreas antigen (anti-SLA/LP) antibodies.* Type 2 autoimmune hepatitis are anti–liver kidney microsome-1 (ALKM-1) antibodies, which are

mostly directed against CYP2D6, and anti–liver cytosol-1 (ACL-1).* associated with the HLA-DR3 , 4 serotype.* it is marked by prominent inflammatory infiltrates of lymphocytes and plasma cells. * elvated gamma globulin and IgG

l47 what are the causes of liver cirrhosis?

what are the morphological change? fibrosis, nodules, lose of architecture, increase portal hydrostatic pressure and sinusoidal hypertension and reduction of the cells.

Perisinuodial stellate cells is the source of collagen in cirrhosiswhat are the clinical manifestations ? and complications? investigations?

L55 acute liver failure: interval between onset of illness and appearance of encephalopathy <26 wfulminant : encephalopathy rapidly develop within 2 weekssub fulminant: jaundice for 3 months(causes) (symptoms)???

Encephalopathy stages associated with liver failure ■ Stage 1: day-night reversal, mild confusion, somnolence■ Stage 2: confusion, drowsiness■ Stage 3: stupor■ Stage 4: coma*herniation is the mc cause of death in fulminant liver failure

L67three forms of alcohol liver diseases: 1) fatty liver 2) alcoholic hepatitis 3) Alcoholic cirrhosis *Gender, Ethnic differences, Genetic and environmental factors, Co-morbi conditions like iron over load, HBV HCV and consumption amount of alcohol. * most common type of ALD is HEPTIC STEATOSIS * What it the pathogenesis? three substrates from alcohol: 1) acetate 2) acetyl coA 3) nadh+H

== inhibits beta oxidation. * what is the pathogenesis of hepatitis? acetaldehyde forms a complex with a protein. the

complex will damage the heptocytes and stimulate the collagen synthesis by Ito cells = leads to perivenular fibrosis. damaged heptocytes will release neutrophills = further damage.

* microscopic findings of alcoholic hepatitis? 6 findings, 1- neutrophils infiltration 2- Mallory bodies (important) 3- focal liver cell necrosis 4- hepatocytes swelling 5- perivenular fibrosis 6- fatty changes

* what are the clinical features and complications ? * alcoholic cirrhosis : fibrous septa, micronodules, shrunken liver. (Masson trichome) L68Classify common benign liver tumors Neoplastic lesions: 1.Hemangioma (Cavernous) 2.AdenomaNon neoplastic lesions: 1-focal nodular hyperplasia 2-cysts

* focal nodular hyperplasia is confused with nodular regenerative hyperplasia, common in young and middle age, its caused by long use of anabolic hormones, contraceptive, (central stellate scar), light and yellowish. WHAT’S THE MORPHOLOGY? 1)central gray white 2)stellate scar with fibrous septa 3)lymphcytes infiltrate 4)bile duct proliferation 5) normal hepatocytes with regeneration

* CYSTS Associated with polycystic kidney, infections. * Cavernous hemangioma is the most common benign liver tumor, fibrous stroma trapping bile

duct, thrombosis, vascular spaces lined with endothelial cells * ADENOMA : neoplastic hepatocytes with no portal tract, central vein or bile duct. more common

in women who have used oral contraceptive, regress if stopped. pathogenesis hormonal stimulation , muation in genes and glycogen storage disease. it’s encapsulated usually right lobe. NOTE: PORTAL TRACTS ABSENT

L71*Hepatoma or Hepatocellular carcinoma is the most common primary liver cancer in adults.60years*predominance in males, what are the causes? risk factors? ….* Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or

cirrhosis* pathogenesis: a mutation to the cellular machinery that causes the cell to replicate at a higher

rate and/or results in the cell avoiding apoptosis* Fibrolamellar HCC affect young people, prognosis is better, it’s a single tumor with fibrous bands* contains bile. green. * MORPHOLOGY: HCC can be unifocal, multi, or diffusely infiltrative cancer or Well-differentiated

HCCs, Moderate- differentiated HCC, Fibrolamellar-HCC* What are the histological findings? metastasis clinical features and complications? l62,l73. go see

Possible mechanism Risk factor

Integration into host genome lead to.disruption& activation proto-oncogenes

Hepatitis-1 B

.Persistent inflammation & cirrhosis .HCV core induced genetic modulation

Hepatitis-2 C

Genetic, mutation of p53 gene Aflatoxin -3B1