الرحيم الرحمن الله الرحيم بسم الرحمن الله بسم

Introduction Introduction

Of pathophysiologyOf pathophysiology

Prof Dr : Yehia El-AlfyProf Dr : Yehia El-Alfy

BIOPSYBIOPSY:: The use of the diseased tissue or cells for diagnostic The use of the diseased tissue or cells for diagnostic

purposes .purposes .

I-TissueI-Tissue : :

1-Tru-cut needle biopsy1-Tru-cut needle biopsy: is carried out with a : is carried out with a wide needlewide needle introduced in introduced in the suspected area to bring a core of tissue (e.g. liver and breast).the suspected area to bring a core of tissue (e.g. liver and breast).

2-Incision biopsy2-Incision biopsy:: It means sampling of a It means sampling of a portion of the diseased tissueportion of the diseased tissue (Punch biopsy) from a mass in lips,skin, nose…..ect).(Punch biopsy) from a mass in lips,skin, nose…..ect).

3-Excision biopsy3-Excision biopsy: The : The entire diseased tissueentire diseased tissue is completely removed is completely removed surgically, surgically,

4- Whole diseased organ4- Whole diseased organ: as breast and its lymph nodes.: as breast and its lymph nodes.

II- CellsII- Cells: Cytological examination are obtained as follow: : Cytological examination are obtained as follow: 1-Aspirated body fluids1-Aspirated body fluids as ascitis, pleural effusion and C.S.F. as ascitis, pleural effusion and C.S.F. 2-Exfoliated cells2-Exfoliated cells in sputum, urine, stools, vaginal and buccal smears. in sputum, urine, stools, vaginal and buccal smears. 3-Fine needle aspiration (FNA)3-Fine needle aspiration (FNA): is the use of a : is the use of a fine needlefine needle to bring cells to bring cells

for cytological examination.for cytological examination.

Growth disordersGrowth disorders

andand

AdaptationAdaptation

Disorders of growth and Disorders of growth and adaptatuinadaptatuin

((1)Increased cellular growth1)Increased cellular growth:: - Hyperplasia.- Hyperplasia. - Hypertrophy.- Hypertrophy.

(2)Decreased cellular growth(2)Decreased cellular growth:: -Agenesis.-Agenesis. -Atrophy.-Atrophy.

(3)Abnormal cellular Differentiation(3)Abnormal cellular Differentiation:: -Metaplasia.-Metaplasia. -Dysplasia.-Dysplasia.

(4)Abnormal purposeless uncontrolled cell growth:(4)Abnormal purposeless uncontrolled cell growth: - - NeoplasiaNeoplasia..

* * Enumerate the disorders of growth and discuss one of them in detailsEnumerate the disorders of growth and discuss one of them in details??

Increased GrowthIncreased Growth**1-1- HypertrophyHypertrophy - Definition- Definition : : IncreaseIncrease in the in the size and weightsize and weight of organs and of organs and

tissues due to increase in the tissues due to increase in the sizesize of their constituent cellsof their constituent cells

- Types- Types : :

1-Physiological hypertrophy1-Physiological hypertrophy (A) Uterine muscles in pregnancy.(A) Uterine muscles in pregnancy.

(B) Skeletal muscles in asthelets(B) Skeletal muscles in asthelets.. 2-Pathological hypertrophy2-Pathological hypertrophy A- Adaptive hypertrophy: As in hollow muscular organs after a chronic partial obstruction. e.g. * Hypertrophy of urinary bladder due to prostatic enlargement, * Hypertrophy of the stomach in pyloric stenosis . * Hypertrophy of Left ventricle in case of hypertension. B- Compensatory hypertrophy: * Best seen in paired organs e.g. after nephrectomy, the other kidney

enlarge in size due to hypertrophy.

**

**2-Hyperplasia2-Hyperplasia

* * DefinitionDefinition: : IncreaseIncrease in the in the size of an organsize of an organ or tissue due to increase or tissue due to increase in the in the numbernumber of its constituent cellsof its constituent cells..

* * Types:Types: 1- Physiological hyperplasia1- Physiological hyperplasia: : e.g.hyperplasia of the breast at puberty and during pregnancy and lactation. e.g.hyperplasia of the breast at puberty and during pregnancy and lactation.

2- Pathological hyperplasia2- Pathological hyperplasia: :

– Compensatory hyperplasiaCompensatory hyperplasia: e.g. formation of regenerating nodules in : e.g. formation of regenerating nodules in liver cirrhosis.liver cirrhosis.

– Hormonal hyperplasiaHormonal hyperplasia: e.g. gynecomastia is marked enlargement of : e.g. gynecomastia is marked enlargement of male breast in adults or due to administration of estrogen in cases of cancer male breast in adults or due to administration of estrogen in cases of cancer prostate.prostate.

– Irritation hyperplasiaIrritation hyperplasia: e.g. hyperplasia of lymphoid tissue in infections : e.g. hyperplasia of lymphoid tissue in infections .. -- Hyperplasia of the covering epitheliumHyperplasia of the covering epithelium::

-After chronic irritation or ulceration in mouth, GIT and respiratory tract-After chronic irritation or ulceration in mouth, GIT and respiratory tract

* Prognosis:* Prognosis: Hyperplasia occurs in response to a Hyperplasia occurs in response to a specific stimulusspecific stimulus, , when it is removedwhen it is removed, the tissue , the tissue

tends to convert to its normal size. Thus it differs from neoplasia in this respect. tends to convert to its normal size. Thus it differs from neoplasia in this respect.

Differentiation between hyperplasia and neoplasiaDifferentiation between hyperplasia and neoplasia

In HyperplasiaIn Hyperplasia: cells are of normal size : cells are of normal size and shape, may have a useful and shape, may have a useful function and stops proliferation on function and stops proliferation on removal of the stimulus.removal of the stimulus.

In neoplasiaIn neoplasia : # # # # # : # # # # #

Diminished growthDiminished growth

Developmental:Developmental:(1) (1) AgenesisAgenesis: complete failure of development.: complete failure of development.

(2) (2) HypoplasiaHypoplasia: failure of development to full mature : failure of development to full mature size. size.

AcquiredAcquired::(1) (1) AplasiaAplasia: : acquired extreme hypoplasia after the acquired extreme hypoplasia after the organ reaches its full maturation, e.g bone marrow.organ reaches its full maturation, e.g bone marrow.

(2) (2) AtrophyAtrophy:: decrease in size and weight of organs decrease in size and weight of organs or tissues due to reduction in size or number of its or tissues due to reduction in size or number of its constituent cells.constituent cells.

AtrophyAtrophyDefinitionDefinition: : DDecreaseecrease in size and weight of organs or tissues in size and weight of organs or tissues

due to reduction in due to reduction in size or numbersize or number of its constituent cells. of its constituent cells.

TypesTypes:: ((1)Physiologic Atrophy1)Physiologic Atrophy: ( due to loss of physiologic : ( due to loss of physiologic

function)function)

11-- Uterus after delivery. Uterus after delivery. 2- Breasts after lactation.2- Breasts after lactation. 3- Gonads after menopause3- Gonads after menopause..

((2)Pathologic atrophy2)Pathologic atrophy::

1-Generalized Atrophy1-Generalized Atrophy::

(1)Starvation atrophy(1)Starvation atrophy: : iin anorexia, malignant cachexia .n anorexia, malignant cachexia .

(2)Senile atrophy(2)Senile atrophy: due to atherosclerotic narrowing of the : due to atherosclerotic narrowing of the arteries.arteries.

(3)Toxic atrophy(3)Toxic atrophy: in chronic wasting diseases as cancers, TB : in chronic wasting diseases as cancers, TB and diabetes.and diabetes.

(4)Endocrine atrophy(4)Endocrine atrophy: as in hypopiuitarism.: as in hypopiuitarism.

22--Localized atrophyLocalized atrophy

(1) Ischemic atrophy(1) Ischemic atrophy:: gradual vascular obstruction --> cerebral gradual vascular obstruction --> cerebral atheroma.atheroma.

(2) Pressure atrophy(2) Pressure atrophy: : pressure --> progressive occlusion of bl. V. pressure --> progressive occlusion of bl. V. asas

-atrophy of vertebrae in syphilitic aortic aneurysm.-atrophy of vertebrae in syphilitic aortic aneurysm.

-brain atrophy in meningioma.-brain atrophy in meningioma.

-Kidney atrophy in hypernephroma.-Kidney atrophy in hypernephroma.

-livercell atrophy in amyloidosis.-livercell atrophy in amyloidosis.

(3) Disuse atrophy(3) Disuse atrophy : : muscle atrophy in casted leg.muscle atrophy in casted leg.

(4) Neuropathic atrophy(4) Neuropathic atrophy : paralysed muscles in poliomyelitis.: paralysed muscles in poliomyelitis.

(5) Endocrine astrophy(5) Endocrine astrophy : : breast atrophy after oopharectomy.breast atrophy after oopharectomy.

))6) Idiopathic atrophy6) Idiopathic atrophy

Abnormalities in cell differentiationAbnormalities in cell differentiation

1-Metaplasia1-MetaplasiaDefinitionDefinition.:.: It is change of one type of differentiated tissue It is change of one type of differentiated tissue

to another type of to another type of the same classthe same class of tissue of tissue..

Causes:Causes: 1 1 -Chronic irritation. 2- Chronic infection.-Chronic irritation. 2- Chronic infection. 3 -Deficiency of certain factors as Vit. A3 -Deficiency of certain factors as Vit. A

Types:Types:(1) Epithelial metaplasia. (2) Connective tissue (1) Epithelial metaplasia. (2) Connective tissue

metaplasia.metaplasia.(3) Mesothelial metaplasia.(3) Mesothelial metaplasia. (4) Tumor (4) Tumor

metaplasia. metaplasia.

Epithelial metaplasiaEpithelial metaplasia(1)Columnar epithelium into squamous epithelium(1)Columnar epithelium into squamous epithelium

-in chronic cholecystitis with stones-in chronic cholecystitis with stones..(2)Transitional epithelium into squamous epithelium(2)Transitional epithelium into squamous epithelium

-in urinary bladder with bilharziasis.-in urinary bladder with bilharziasis.

(3) Pseudostratified columnar ciliated to squamous(3) Pseudostratified columnar ciliated to squamous::--In chronic bronchitis with smoking and infection.In chronic bronchitis with smoking and infection.

22--DysplasiaDysplasiaDefinitionDefinition:: It is a disordered cellular proliferation. It is a disordered cellular proliferation.

Characters of dysplastic cellsCharacters of dysplastic cells::-Pleomorphism (Variation in size and shape(.-Pleomorphism (Variation in size and shape(.-Loss of polarity (orientation)-Loss of polarity (orientation)-Hyperchromatic nuclei ( deep basophilic staining).-Hyperchromatic nuclei ( deep basophilic staining).-Presence of mitosis.-Presence of mitosis.

* Usually associated with chronic irritation* Usually associated with chronic irritation..

FateFate: : Although it is potentially reversible it is a premalignant lesion Although it is potentially reversible it is a premalignant lesion that can progress into cancer.that can progress into cancer.

Grading of dysplasiaGrading of dysplasia **Grade IGrade I dysplasia taking dysplasia taking lower 1/3lower 1/3 of the thickness of cells. of the thickness of cells. **Grade IIGrade II dysplasia taking dysplasia taking lower 2/3lower 2/3 of the thickness of cells. of the thickness of cells. **Grade IIIGrade III dysplasia taking dysplasia taking the wholethe whole thickness of cells. thickness of cells.

Examples of dysplasiaExamples of dysplasia

1-1-Dysplasia of the Dysplasia of the urinary bladderurinary bladder with with bilharziasis.bilharziasis.

2-Dysplasia in 2-Dysplasia in uterine cervixuterine cervix with chronic cervicitis with chronic cervicitis

3-Dysplasia in 3-Dysplasia in gall bladdergall bladder with chronic with chronic cholecystitis.cholecystitis.

4-Dysplasia in 4-Dysplasia in bronchial epitheliumbronchial epithelium with with ch.bronchitis.ch.bronchitis.

5-Dysplasia in the 5-Dysplasia in the oral cavity oral cavity inin dental caries.dental caries.

Cell InjuryCell Injury DefinitionDefinition:: Metabolic and Morphological changes in the cells , Metabolic and Morphological changes in the cells ,

may be reversible (injury may be reversible (injury not enoughnot enough to damage to damage nucleinuclei and and cause cell death), or irreversible ( cell death).cause cell death), or irreversible ( cell death).

Types:Types: 1-Reversible1-Reversible: : Caused by mild injury and can be reversed by Caused by mild injury and can be reversed by

repair mechanismsrepair mechanisms2-Irreversible2-Irreversible: : Caused by severe injury which results in cell Caused by severe injury which results in cell

death by one of two mechanisms : a- necrosis (cells simply die)death by one of two mechanisms : a- necrosis (cells simply die)

b- apoptosis (programmed cell deathb- apoptosis (programmed cell death) ) Causes of Cell InjuryCauses of Cell Injury (1)Hypoxia(1)Hypoxia: : decrease of bl. supplydecrease of bl. supply (2)Physical(2)Physical : : mechanical trauma, burn.electric.mechanical trauma, burn.electric. (3)Chemicals(3)Chemicals: : drugs, drugs, Strong acids or alkalines,smoke,heavy metalsStrong acids or alkalines,smoke,heavy metals.. (4)Microbiologic(4)Microbiologic : : Bacteria,viruses, parasitresBacteria,viruses, parasitres…… ((5)Immunologic Reactions5)Immunologic Reactions (6)Radiation(6)Radiation : : ionizing rad.,x-rays, microwavesionizing rad.,x-rays, microwaves..

(7)Nutritional(7)Nutritional : : malnutrition, obesitymalnutrition, obesity..

Mechanisms of cell injuryMechanisms of cell injury: :

It depends on the type of injury, its duration, and severity , Cell type, state, and It depends on the type of injury, its duration, and severity , Cell type, state, and adaptability are also responsible. adaptability are also responsible.

These mechanisms includeThese mechanisms include::

1-ATP depletion1-ATP depletion: :

It leads to defects in vital cellular processes (membrane transport and protein It leads to defects in vital cellular processes (membrane transport and protein synthesis). It's a common sequence of ischemic and toxic injury due to defects in synthesis). It's a common sequence of ischemic and toxic injury due to defects in oxidative phosphorylation of ADP. oxidative phosphorylation of ADP.

2-Free radical damage (Oxygen derived free radicals2-Free radical damage (Oxygen derived free radicals)):: *Source*Source: : are generated as products of are generated as products of normal cell metabolism (normal cell metabolism (in many oxidative in many oxidative

processes in the cells as a products of mitochondrial respiration ) processes in the cells as a products of mitochondrial respiration ) ** Free Radical Injury Contributes ToFree Radical Injury Contributes To::

– Chemical and radiation injuryChemical and radiation injury– Oxygen and other gaseous toxicityOxygen and other gaseous toxicity– Cellular agingCellular aging– Microbial killing by phagocytic cellsMicrobial killing by phagocytic cells– Inflammatory damageInflammatory damage– Tumor destruction by macrophagesTumor destruction by macrophages– OthersOthers

* Examples* Examples: as superoxide, hydrogen peroxide, hydroxyl ions and nitric acid .and inactivated by some : as superoxide, hydrogen peroxide, hydroxyl ions and nitric acid .and inactivated by some body enzymes as: catalase and glutathione peroxidase.body enzymes as: catalase and glutathione peroxidase.• Exogenous sourcesExogenous sources of free radicals include tobacco smoke, pollutants, radiation, … of free radicals include tobacco smoke, pollutants, radiation, … • Free radical injury has Free radical injury has a key rolea key role in the normal aging process, beside a number of diseases as in the normal aging process, beside a number of diseases as

diabetes mellitus, AS, cancer, Alzheimer’s dis., and RH. Arthritisdiabetes mellitus, AS, cancer, Alzheimer’s dis., and RH. Arthritis . .

* * Free Radical Cell Injury Mechanism:Free Radical Cell Injury Mechanism: 1- 1- Damage of membrane lipids. 2- Damage of cellular proteins.Damage of membrane lipids. 2- Damage of cellular proteins. 3- Mutation of cellular DNA.3- Mutation of cellular DNA.

3- Disturbance of intracellular calcium 3- Disturbance of intracellular calcium : : Ischemia and some toxins cause early increase Ischemia and some toxins cause early increase in cytoplasmic calcium by increase Ca influx across the plasma membrane and release of Ca in cytoplasmic calcium by increase Ca influx across the plasma membrane and release of Ca from mitochondria from mitochondria It activates enzymes causing cell damaging as, phospholipases, It activates enzymes causing cell damaging as, phospholipases, proteases proteases ..

4- Defects in membrane permeability4- Defects in membrane permeability: : It's a feature of all forms of cell injuryIt's a feature of all forms of cell injury. It is due to either direct damage of cell membrane e.g. . It is due to either direct damage of cell membrane e.g.

bacterial toxins or ATP depletionbacterial toxins or ATP depletion. .

5- Mitochondrial damage5- Mitochondrial damage:: Mitochondria are targets for all types of injurious stimuliMitochondria are targets for all types of injurious stimuli e.g. hypoxia and oxidative stress. e.g. hypoxia and oxidative stress.

Damage is reversible in early stages but if the injurious agent persists, it becomes irreversible Damage is reversible in early stages but if the injurious agent persists, it becomes irreversible leading to cell death through disturbance of oxidative phosphorylationleading to cell death through disturbance of oxidative phosphorylation

General morphological changes in cell General morphological changes in cell injuryinjury::

A- Nuclear changes:A- Nuclear changes: Consist of clumping of Consist of clumping of chromatinchromatin and smaller but more numerous and smaller but more numerous

nucleolinucleoli with loss of their granular component, which indicates with loss of their granular component, which indicates impaired synthesis of ribosomal material . Detected by light impaired synthesis of ribosomal material . Detected by light microscopymicroscopy..

B- Cytoplasmic changes: B- Cytoplasmic changes: 1- Evidence of hyperfunction1- Evidence of hyperfunction: Increase the number and : Increase the number and

complexity of cell organelles.complexity of cell organelles. 2- Evidence of hypofunction2- Evidence of hypofunction: loss of ribosomes leading to : loss of ribosomes leading to

impaired protein synthesis. Mitochondria are swollen with icreased impaired protein synthesis. Mitochondria are swollen with icreased calcium content calcium content decrease oxidative phosphorylation. decrease oxidative phosphorylation.

3- Evidence of altered function3- Evidence of altered function: e.g. cilia may develop in cells : e.g. cilia may develop in cells not normally ciliated (cells of olfactory mucosa).not normally ciliated (cells of olfactory mucosa).

4- Abnormal accumulation of substances4- Abnormal accumulation of substances in the cells: e.g. in the cells: e.g. lipids.lipids.

5- Degenerative changes5- Degenerative changes: Focal cytoplasmic degeneration and : Focal cytoplasmic degeneration and autophagocytic vacuoles are increased in number. autophagocytic vacuoles are increased in number.

1-REVERSIBLE CELL INJURY1-REVERSIBLE CELL INJURY

DefinitionDefinition: : It is reversible morphological changes that affect It is reversible morphological changes that affect

cells. they includecells. they include:: I)- Changes associated with disturbance of water I)- Changes associated with disturbance of water

metabolismmetabolism

a-a- Cloudy swellingCloudy swelling- It is a reversible cell damage characterized by accumulation of It is a reversible cell damage characterized by accumulation of

waterwater inside the cells (cellular edema) inside the cells (cellular edema).It is due to .It is due to mitochondrial injurymitochondrial injury

b -Hydropic (vacuolar) degenerationb -Hydropic (vacuolar) degeneration -- It is closely related to cloudy swelling but there is It is closely related to cloudy swelling but there is marked marked

increase in the permeability of the cell membrane to water inside increase in the permeability of the cell membrane to water inside the cell, which appears either in the form of multiple small droplets the cell, which appears either in the form of multiple small droplets or as a single large vacuole which distends the cells.or as a single large vacuole which distends the cells.

* It may occur in epidermal cells in burns, liver cells in virus * It may occur in epidermal cells in burns, liver cells in virus hepatitis, islets of Langerhans in some cases of diabetes.hepatitis, islets of Langerhans in some cases of diabetes.

II)- Changes associated with disturbances of fat II)- Changes associated with disturbances of fat metabolismmetabolism

a- Fatty change (steatosis)a- Fatty change (steatosis) It means abnormal accumulation of neutral fat It means abnormal accumulation of neutral fat (Triglycerides)(Triglycerides)

within parenchymal cells mainly liver, and includes: within parenchymal cells mainly liver, and includes:

1-Fatty degeneration1-Fatty degeneration : (Damaged cells can not metabolize : (Damaged cells can not metabolize lipids ) lipids )

2-Fatty infiltration:2-Fatty infiltration: (Increase of fat entry to the cells). (Increase of fat entry to the cells). Pathogenesis of fatty change in the liverPathogenesis of fatty change in the liver : : 1-Excessive starvation1-Excessive starvation mobilization of fat to liver from fat mobilization of fat to liver from fat

stores.stores. 2-Viral hepatitis2-Viral hepatitis: : Diseased liver cells can not metabolize normal Diseased liver cells can not metabolize normal

reaching fat to the liver.reaching fat to the liver. 3- Defeciency of lipotropic factors3- Defeciency of lipotropic factors as choline and as choline and

methionine. which transform neutral fat to a form most of the body methionine. which transform neutral fat to a form most of the body cells can utilize it.cells can utilize it.

22 - -Irreversible cell injury (Cell death)Irreversible cell injury (Cell death) Types of cell deathTypes of cell death : 1- Apoptosis. 2- Necrosis : 1- Apoptosis. 2- Necrosis..1- APOPTOSIS:1- APOPTOSIS: DefinitionDefinition:: It is a programmed ( controlled) cell death occurs with aging and It is a programmed ( controlled) cell death occurs with aging and

normal wear and tear of the cellnormal wear and tear of the cell ApoptosisApoptosis may be a mechanism to may be a mechanism to eliminate damaged cellseliminate damaged cells. Certain viruses as . Certain viruses as

(Epstein Barr virus) may activate apoptosis within an infected cell, thus killing both (Epstein Barr virus) may activate apoptosis within an infected cell, thus killing both the host cell and infecting virusthe host cell and infecting virus..

ApoptosisApoptosis may involve the activation of certain ( suicide genes) which in response may involve the activation of certain ( suicide genes) which in response to certain chemical signals activate and lead to cell lysis and destructionto certain chemical signals activate and lead to cell lysis and destruction..

It has been theorized that It has been theorized that cancercancer may arise as may arise as a failurea failure of normal apoptosis in of normal apoptosis in

damaged or mutated cellsdamaged or mutated cells..

Types of apoptosis:Types of apoptosis:(1) Physiological apoptosis(1) Physiological apoptosis::

Hormone-dependent involution, such as endometrial breakdown during the Hormone-dependent involution, such as endometrial breakdown during the menstrual cycle. menstrual cycle.

(2) Pathological apoptosis(2) Pathological apoptosis::

- Cell death produced by a variety of injurious stimuli as radiation, and - Cell death produced by a variety of injurious stimuli as radiation, and cytotoxic anticancer drugs damage DNA, and if repair mechanisms cytotoxic anticancer drugs damage DNA, and if repair mechanisms cannot cope with the injury, the cell kill itself by apoptosis.cannot cope with the injury, the cell kill itself by apoptosis.

- Cell injury in certain viral diseases as viral hepatitis.- Cell injury in certain viral diseases as viral hepatitis.

* * Fate of apoptosisFate of apoptosis Phagocytosis of apoptotic cells or cell bodies by macrophages. The Phagocytosis of apoptotic cells or cell bodies by macrophages. The

adjacent healthy cells migrate or proliferate to replace the space occupied adjacent healthy cells migrate or proliferate to replace the space occupied by the apoptotic cell. The plasma membranes remain intact during by the apoptotic cell. The plasma membranes remain intact during apoptosis, until the last stages, then it become permeable to normally apoptosis, until the last stages, then it become permeable to normally retained solutes.retained solutes.

2- NECROSIS2- NECROSIS * * DefinitionDefinition:: It is local death of small or large groups of cells in It is local death of small or large groups of cells in

a living tissue.a living tissue.

* * Causes:Causes: 1- Cut of blood supply1- Cut of blood supply 2- Trauma2- Trauma 3- Bacterial toxins3- Bacterial toxins 4- Physical and chemical agents4- Physical and chemical agents 5- Hypersensitivity reactions 5- Hypersensitivity reactions

Types of necrosisTypes of necrosis

1- Coagulative necrosis1- Coagulative necrosis: :

- It is due to cut of blood supply by thrombosis and embolism.- It is due to cut of blood supply by thrombosis and embolism.

2- Liquefactive necrosis2- Liquefactive necrosis:: -AS in pyogenic abscess, amoebic abscess and CNS infections.-AS in pyogenic abscess, amoebic abscess and CNS infections.

3- Caseous necrosis3- Caseous necrosis::

- AS in T.B. infection. The term caseous is derived from the cheesy white - AS in T.B. infection. The term caseous is derived from the cheesy white appearance of the necrotic area. appearance of the necrotic area.

4- Fat necrosis4- Fat necrosis::

- It describes focal areas of fat destruction, typically occurring as a result of - It describes focal areas of fat destruction, typically occurring as a result of acute pancreatitis due to release of activated pancreatic enzymes into the acute pancreatitis due to release of activated pancreatic enzymes into the substance of the pancreas or the peritoneal cavity. The enzymes liquefy substance of the pancreas or the peritoneal cavity. The enzymes liquefy fat cell membranes, and split the triglyceride esters. fat cell membranes, and split the triglyceride esters.

Cells of inflammationCells of inflammation**1-1- Polymorphnuclear leucocytesPolymorphnuclear leucocytes (PNLs) or (microphages): (PNLs) or (microphages):

They phagocytose bacteria and necrotic tissue.They phagocytose bacteria and necrotic tissue.

*2- *2- MacrophagesMacrophages: derived from blood monocytes and tissue : derived from blood monocytes and tissue histiocytes: histiocytes: a- Attack bacteria with fatty sheath as T.B. as a- Attack bacteria with fatty sheath as T.B. as they contain enzyme lipase. they contain enzyme lipase.

b- Phagocytose necrotic tissue.b- Phagocytose necrotic tissue.

C-Formation of giant cellsC-Formation of giant cells..

*3-*3-EosinophilsEosinophils : in allergic and parasitic inflammation. : in allergic and parasitic inflammation.

*4- *4- LymphocytesLymphocytes: Give rise to plasma cells. : Give rise to plasma cells.

*5*5- - Plasma cellsPlasma cells : form antibodies. : form antibodies.

*6-*6- Foreign body giant cellsForeign body giant cells: formed by fusion several : formed by fusion several macrophages and phagocytose foreign bodies.macrophages and phagocytose foreign bodies.

55 Cardinal Signs of InflammationCardinal Signs of Inflammation

1-Redness1-Redness <- vasodilatation and Hyperaemia.<- vasodilatation and Hyperaemia.

2- Hotness2- Hotness <– Increased blood flow and Hyperaemia. <– Increased blood flow and Hyperaemia.

3-Pain3-Pain <– irritation of nerve endings by products of <– irritation of nerve endings by products of inflammation and pressure by inflammatory exudate.inflammation and pressure by inflammatory exudate.

4-Swelling4-Swelling <– Inflammatory Exudate +vasodilatation. <– Inflammatory Exudate +vasodilatation.

5-Loss of Function5-Loss of Function due to pain and tissue damage.due to pain and tissue damage.

Varieties of acute inflammationVarieties of acute inflammation A- Non-suppurative inflammationsA- Non-suppurative inflammations:-:- 1. Catarrhal inflammation as: 1. Catarrhal inflammation as: Rhinitis.Rhinitis. 2. Fibrinous inflammation as : 2. Fibrinous inflammation as : Lobar pneumoniaLobar pneumonia.. 3. Serous inflammation : as: 3. Serous inflammation : as: BurnsBurns.. 4. Serofibrinous inflammation as: 4. Serofibrinous inflammation as: PPPPPP 5. Membranous inflammation5. Membranous inflammation as: as: Diphtheria.Diphtheria. 6. Allergic inflammation as:6. Allergic inflammation as: Urticaria Urticaria.. 7. Hemorrhagic inflammation7. Hemorrhagic inflammation as: In as: In betahaemolytic betahaemolytic

Strep.infectionStrep.infection 8. Necrotizing inflammation.as : 8. Necrotizing inflammation.as : gangrene.gangrene.

B- Suppurative inflammationsB- Suppurative inflammations:-:- 1-Localized (abscess, boil, carbuncle)1-Localized (abscess, boil, carbuncle) 2-Diffuse (cellulitis)2-Diffuse (cellulitis)

Healing by 1st intentionHealing by 2nd intention

The 2 ends are approximatedThe 2 ends are non approximated

Clean woundInfected wound

No necrotic tissueNecrotic tissue is found

Tissue deprisNo tissue depris

Short time to be healedLong time to be healed

Small scarMuch larger scar

Epithelial growth is the firstGranulation tissue is the first

Cytokines Definition :Soluble proteins secreted by lymphocytes

(lymphokines), monocytes-macrophages (monokines).-Act as effector molecules affecting the behavior of B cells, T cells, NK cells, monocytes, macrophages, and other cell types.

Examples: Interleukins "1 to 8", Interferons "(IFN-α), (IFN-β), (IFN-γ)" and Tumor necrosis factors "(TNF-α), (TNF-β).

LymphokinesLymphokines- - A soluble proteins secreted by lymphocytes.A soluble proteins secreted by lymphocytes.1. Chemotactic factors1. Chemotactic factors: : - Attracts neutrophils and macrophages.- Attracts neutrophils and macrophages.2. Migration inhibition factor (MIF):2. Migration inhibition factor (MIF): - Helps in granuloma formation.- Helps in granuloma formation.3. Mitogenic factor3. Mitogenic factor:: - Stim.mitoses of lymphocytes- Stim.mitoses of lymphocytes

4. Cytotoxic factor4. Cytotoxic factor: : - Destroying cells, causing caseous necrosis of epithelioid - Destroying cells, causing caseous necrosis of epithelioid

cells of T.B.cells of T.B.5. Transfer factor5. Transfer factor: : - Transfer sensitization to new lymphocytes.- Transfer sensitization to new lymphocytes.6. Interferon6. Interferon: antiviral.: antiviral.

InterferonsInterferons Proteins usually produced by virally infected cellsProteins usually produced by virally infected cells

* * Types of interferonsTypes of interferons::1- Alpha interferon : 1- Alpha interferon : Secreted by macrophagesSecreted by macrophages

Induced by viruses or polynucleotide.Induced by viruses or polynucleotide. 2- Beta interferon: 2- Beta interferon: Secreted by fibroblasts, viruses, Secreted by fibroblasts, viruses, 3- Gamma interferon: 3- Gamma interferon: secreted by T- lymphocytes and specific secreted by T- lymphocytes and specific

antigensantigens

* * Protective action of interferonsProtective action of interferons:: 1) Activate T-cells1) Activate T-cells 2) Activate macrophages2) Activate macrophages 3) Activate NK3) Activate NK

Risk GroupsRisk Groups11 . .Homosexual males (60%)Homosexual males (60%)

22 . .Intravenous drug abusers (24%)Intravenous drug abusers (24%)33 . .Hemophiliacs (1%)Hemophiliacs (1%)

44 . .Other blood recipients (2%)Other blood recipients (2%)55 . .Heterosexual partners of other high-risk Heterosexual partners of other high-risk

group members group members66 . .children of parents from groups 1.-3children of parents from groups 1.-3..

..

3 Clinical stages of HIV(1) Acute phase stage:(1) Acute phase stage:(2)Asymptomatic (2)Asymptomatic

stage(Latent phase)stage(Latent phase)(3) Symptomatic or (3) Symptomatic or

(AIDS stage)(AIDS stage)

- 2-4 - 2-4 weeks after weeks after infection.infection.

- Symptoms of acute - Symptoms of acute illness.

(Fever,fatigue…)…)

-Transient reduction of -Transient reduction of CD8+, CD4+ number.CD8+, CD4+ number.

-Symptoms disappear -Symptoms disappear later later asymptomatic asymptomatic

- - Long period 5-10 Long period 5-10 years) free of infection years) free of infection

symptoms.symptoms.

- - Slow persistent Slow persistent destruction of destruction of

immune cellsimmune cells decrease number of decrease number of

circulating CD4+ circulating CD4+ lymphocytes and CD8+ lymphocytes and CD8+

lymphocytes lymphocytes

- - Marked decrease in Marked decrease in CD4+ lymphocytesCD4+ lymphocytes

-AIDS-related complex -AIDS-related complex (ARC): fever, night (ARC): fever, night

sweats, diarrhea andsweats, diarrhea and

**opportunistic opportunistic infectionsinfections

1-1-Tumors: Kaposi' Tumors: Kaposi' sarcomasarcoma

2-2-Neurologic: Neurologic: dementia complex dementia complex Loss of memoryLoss of memory, ,

MalignantMalignantNot well cirumscribed,Not well cirumscribed, Usually larger in size,Usually larger in size, Fast growing, Fast growing, non capsulated, non capsulated, Invasive & Infiltrate Invasive & Infiltrate Hge and necrosis.Hge and necrosis. Metastasize. Metastasize. poorly differentiated, poorly differentiated, Suffix “Carcinoma” or Suffix “Carcinoma” or

“Sarcoma”“Sarcoma”

BenignBenign Well circumscribed,Well circumscribed, Usually small in size,Usually small in size, Slow growing,Slow growing, capsulated, capsulated, Non-invasive Non-invasive No hge. and necrosisNo hge. and necrosis do not metastasize, do not metastasize, well differentiated, well differentiated, suffix “oma” eg. suffix “oma” eg.

Fibroma.Fibroma.

Signs of malignancySigns of malignancy

CellularCellular Dysplasia Dysplasia (different (different

from tissue of origin)from tissue of origin) DisorganizationDisorganization Loss of polarity.Loss of polarity. Pleomorphism Pleomorphism

(variable in size and (variable in size and shape)shape)

Loss of cohesionLoss of cohesion.. Presence of giant Presence of giant

cellscells

NuclearNuclear Large nucleiLarge nuclei Hyperchromasia.Hyperchromasia. N/C ratio high.N/C ratio high. Pleomorphic Pleomorphic

nuclei.nuclei. Prominent Prominent

nucleoli.nucleoli. Frequent mitoses.Frequent mitoses. Abnormal mitotic Abnormal mitotic

figures.figures.

Functional: Loss of normal function of the cell

Spread of Spread of malignant tumoursmalignant 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.

What is a “Tumor MarkerWhat is a “Tumor Marker?”?”

A A tumor markertumor marker is a substance present in or produced by a is a substance present in or produced by a tumor or by the tumor’s host in response to the tumor’s tumor or by the tumor’s host in response to the tumor’s presence presence

It can be used:It can be used:• • to differentiate a tumor from normal tissue or to differentiate a tumor from normal tissue or• to determine the presence of a tumor.• to determine the presence of a tumor.

Such a substance can be found in:Such a substance can be found in:• cells• cells• tissues• tissues• body fluids• body fluids

It can be measured qualitatively or quantitatively by:It can be measured qualitatively or quantitatively by:• chemical• chemical• immunological• immunological• molecular biological methods• molecular biological methods

Types of Tumor MarkersTypes of Tumor Markers Cellular Cellular (tissue tumor markers): (tissue tumor markers):

detected in tissuesdetected in tissues.. Humoral Humoral (present in blood and (present in blood and

body fluids:body fluids:– HormonesHormones (hCG; calcitonin; gastrin; prolactin; (hCG; calcitonin; gastrin; prolactin;

growth hormone, etc.)growth hormone, etc.)

– EnzymesEnzymes (acid phosphatase; alkaline (acid phosphatase; alkaline phosphatase; PSA)phosphatase; PSA)

– Proteins & GlycoproteinsProteins & Glycoproteins (CA 125; CA (CA 125; CA 15.3; CA 19.9, etc.)15.3; CA 19.9, etc.)

– Oncofetal antigensOncofetal antigens (CEA, AFP) (CEA, AFP)– ReceptorsReceptors (ER, PR, EGFR) (ER, PR, EGFR)– Oncogenes Oncogenes (Ras; Myc; abl-bcr)(Ras; Myc; abl-bcr)– Tumor suppressor genesTumor suppressor genes (BRCA1; (BRCA1;

p53; Rb)p53; Rb)

Characteristics of the “Ideal” Tumor Characteristics of the “Ideal” Tumor MarkerMarker

11--Measured easily, reliable, and Measured easily, reliable, and cost-effectivelycost-effectively

22--High sensitivityHigh sensitivity

33--High specificityHigh specificity..

44--Organ specificity.( PSA for Organ specificity.( PSA for prostate…….)prostate…….)

55--Correlated with tumor stageCorrelated with tumor stage..66--Corelated with prognosisCorelated with prognosis

Clinical Uses of Tumor Clinical Uses of Tumor MarkersMarkers

••ScreeningScreening for cancer for cancer (Alfa feto protein for (Alfa feto protein for liver cancer) liver cancer)

••DiagnosingDiagnosing cancer cancer – (pelvic mass)– (pelvic mass)••Evaluating prognosisEvaluating prognosis of cancer- of cancer-(CEA in (CEA in

colon cancer)colon cancer)••Tumor stagingTumor staging--

••Detecting Tumor Recurrence or Detecting Tumor Recurrence or remissionremission--

••Localizing tumorLocalizing tumor and directing chemo- or radio-and directing chemo- or radio-

therapeutic agents-therapeutic agents- ••Monitoring the effectivenessMonitoring the effectiveness of cancer of cancer

therapytherapy

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

4-4-Luteinizing hormone (LH).Luteinizing hormone (LH).

Stimulates testosterone production and induction of Stimulates testosterone production and induction of ovulation ( secretory function of the corpus luteum)ovulation ( secretory function of the corpus luteum)..

5- 5- Follicle-stimulating hormone (FSH)Follicle-stimulating hormone (FSH) . . Help spermatogenesis and maturation of ova.Help spermatogenesis and maturation of ova.

6-6-Prolactin (PRL).Prolactin (PRL).

- - Initiates and maintains milk production in the mammary Initiates and maintains milk production in the mammary glands postpartum.glands postpartum.

))BB ( (Hormones of the posterior pituitaryHormones of the posterior pituitary

1-1- (Oxytocin)(Oxytocin):: On uterusOn uterus : : Stimulates contraction of uterine Stimulates contraction of uterine

smooth muscle during labor.smooth muscle during labor. On breastOn breast : : stim. milk ejection from the stim. milk ejection from the

mammary glandsmammary glands

2-2- Antidiuretic hormone (ADHAntidiuretic hormone (ADH, , vasopressinvasopressin) ) - Stimulate water reabsorption in - Stimulate water reabsorption in the collecting ducts of the kidney.the collecting ducts of the kidney.

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.

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

Growth hormone hypersecretion 1-Gigantismresults 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).

TreatmentSurgical removal of tumor.Radiation therapy of the tumor if surgery is not feasible.

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

Diabetes insipidusB- Decreased production of ADH.

Etiology :Decreased ADH is due to defects in the hypothalamus/ pituitary

axis or from a tumor or trauma.Manifestations

Polyuria : Excessive production of very dilute urine. Polydypsia : Excessive thirst.

Dehydration : Increased plasma osmolarity. Hypotension and reflex tachycardia.

Treatment* Administration of ADH and ADH analogues like lypressin and desmopressin * ADH itself is administered by S.C. or I.M. injection, whereas lypressin and

desmopressin are administered as an intranasal spray. * An oral form of desmopressin is also now available.

Alterations of thyroid functionAlterations of thyroid functionHypothyroidism.Hypothyroidism.1- Primary condition1- Primary condition : : Resulting from a defect within the thyroid gland Resulting from a defect within the thyroid gland

itself ( surgical removal, infection, tumour , itself ( surgical removal, infection, tumour , radiation…..)radiation…..)

2- Secondary :2- Secondary : 1-Due to defect in hypothalamus or pituitary 1-Due to defect in hypothalamus or pituitary

glandgland 2-Dietary deficiency of iodine 2-Dietary deficiency of iodine hypertrophy hypertrophy

of the thyroid gland that presents as a goiterof the thyroid gland that presents as a goiter

Manifestations of hypothyroidismManifestations of hypothyroidism:: 1-In fetal life ( Cretinism).1-In fetal life ( Cretinism). 2-In adults ( Myxedema).2-In adults ( Myxedema).

– 1- 1- CretinismCretinism– Occurs during fetal development as a result of congenital Occurs during fetal development as a result of congenital

defect in thyroid development and characterized by defect in thyroid development and characterized by Poor overall development and growth retardation.as Poor overall development and growth retardation.as * Serious retardation of mental and physical development * Serious retardation of mental and physical development

(dwarf, thick,flabby waxy skin,flat nose, protruded (dwarf, thick,flabby waxy skin,flat nose, protruded tongue ,pot-belly abdomen,loss of teeth and hair,umbilical tongue ,pot-belly abdomen,loss of teeth and hair,umbilical hernia)hernia)

2-Myxedema2-Myxedema Hypothyroidism in the adultHypothyroidism in the adult May result from autoimmune destruction of the thyroid or May result from autoimmune destruction of the thyroid or

thyroid injury or removal.thyroid injury or removal. Presents with signs of Presents with signs of hypometabolismhypometabolism including: including: Cold intolerance, Weight gain, Fatigue, Bradycardia, Cool, Cold intolerance, Weight gain, Fatigue, Bradycardia, Cool,

dry skin, Anorexia, Constipation, Edema of the face dry skin, Anorexia, Constipation, Edema of the face (swelling around the eyes), hands and ankles; drooping (swelling around the eyes), hands and ankles; drooping eyelidseyelids

* * These changes are reversible with thyroid hormone These changes are reversible with thyroid hormone therapytherapy

TreatmentTreatment Thyroid hormone replacement therapy.Thyroid hormone replacement therapy. A variety of synthetic and natural T3 /T4 preparations are A variety of synthetic and natural T3 /T4 preparations are

available for use orally.available for use orally.

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)

Grave's diseaseGrave's disease

DefinitionDefinition: : It is autoimmune disease that considered as It is autoimmune disease that considered as

one of the most common causes of hyperthyroidismone of the most common causes of hyperthyroidism.. MechanismMechanism: : Autoantibodies Autoantibodies that bind TSH receptors that bind TSH receptors

on the thyroid and mimic the actions of TSH on the thyroid and mimic the actions of TSH excess excess production of thyroid hormones.production of thyroid hormones.

ManifestationsManifestations1-Increased basal metabolic1-Increased basal metabolic rate rate Increased heat Increased heat

production, patient always feels production, patient always feels ""hot",hot", Tachycardia, Tachycardia, Increased catecholamine sensitivity; patients are at risk Increased catecholamine sensitivity; patients are at risk for cardiac arrhythmias, Increased appetite, Weight loss, for cardiac arrhythmias, Increased appetite, Weight loss, Enhanced bowel activityEnhanced bowel activity diarrhea diarrhea..

2- Nervousness , excitability and bad dreams2- Nervousness , excitability and bad dreams..

TreatmentTreatment

1-Antithyroid drugs1-Antithyroid drugs (propyl-thiouracil, carbimazole (propyl-thiouracil, carbimazole block production of thyroid hormones. block production of thyroid hormones.

2-Beta -Blockers2-Beta -Blockers drugs to blunt the effects of drugs to blunt the effects of excess adrenergic stimulation.excess adrenergic stimulation.

3-Radioiodine3-Radioiodine: It is given orally.: It is given orally.

4-Surgical ablation4-Surgical ablation of a portion of the thyroid ( of a portion of the thyroid ( partial thyroidectomy).partial thyroidectomy).

Diabetes mellitusRisk Factors for Diabetes Mellitus

1.Obesity.

2.Familial history of diabetes mellitus.

3.Increasing age.

4.Dietary factors.

Types of diabetes mellitusType 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)

4- 4- Weakness and fatigue: Weakness and fatigue:

* * Due to poor energy utilization and skeletal muscle Due to poor energy utilization and skeletal muscle catabolismcatabolism

5-Diabetic ketoacidosis : 5-Diabetic ketoacidosis : * Accumulation of acidic ketone bodies in the blood due * Accumulation of acidic ketone bodies in the blood due

to a lack of insulin-stimulated fatty acid utilizationto a lack of insulin-stimulated fatty acid utilization).).

TreatmentTreatment Insulin replacement therapyInsulin replacement therapy Dietary managementDietary management

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

Mechanisms of Tissue Injury inChronic 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.

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

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.

5. Diabetic retinopaathy5. Diabetic retinopaathy1-1- Retinal damage due chronic hvpoxemia,Retinal damage due chronic hvpoxemia,

2-Hemorrhage of eye capillaries and chronic 2-Hemorrhage of eye capillaries and chronic inflammation inflammation increases in intraocular pressure increases in intraocular pressure that scar the retina and impair vision that scar the retina and impair vision blindness. blindness.

3-Diabetes is also associated with an increased 3-Diabetes is also associated with an increased incidence of glucoma and cataract formation.incidence of glucoma and cataract formation.

A- Genetic Defects1-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.

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.

*Gastro-esophageal refluxDefinition :-Backflow of gastric contents into the esophagusCause :- 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 ulceration3-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.

Treatment:-Medical treatment1-Eating of small frequent meals 2-Sleeping with elevated head3-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.

Peptic ulcersDefinition:- 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

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 rate5-G.I.T obstruction (fibrosis)

Treatment of peptic ulcer :-1-Avoidance of alcohol ,smoking and NSAIDS2-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

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 cytokinesPathology :- -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 .

Manifestations :-1-Anorexia ,nausea and vomiting 2-Fever3-Bloody diarrhea. 4-Abdominal pain 5-Loss of weight from malabsorption6-Fibrosis and intestinal obstruction 7-Abdominal fistula ,between colon and abdominal wallTreatment :- 1-Nutritional support and total parenteral nutrition in severe cases.2-Anti-inflammatory drugs 3-Blocking the action of cytokines by drugs or antibodies.

 

Ulcerative colitisDefinition:-Chronic ulcero-inflammatory diseases affects the distal colon (rectum and colon) and extends backward (back-wash ileitis)Etiology :- 1-Idiopathic2-Genetic or immunologic disordersPathology :- 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 anemia4-The possibility of perforated intestine ,blood loss and cancer colon.

Treatment :-1-Nutritional support 2-Surgical resection of the diseased part to reduce incidence of cancer3-Anti-inflammatory drugs and salicylates to suppress inflammation.4-Sulfasalazine drug (sulfa and aminosalicylate) 5-Nicotine exerts a protective effect in ulcerative colitis .

ItemItemCrohn`s Crohn`s diseasedisease

U.colitisU.colitis

Age of onsetAge of onset

LocationLocation

InflammationInflammation

Skip lesions Skip lesions

Layers Layers involved involved Bloody stool Bloody stool MalabsorptioMalabsorptionn

UlcersUlcers

Crypt Crypt abscessesabscesses

Propensity Propensity for for malignancy malignancy

20-40 years20-40 years

Any part of GIT at ileo-Any part of GIT at ileo-cecal regioncecal region

Granulomatous Granulomatous inflamm. inflamm.

presentpresent

Through the wallThrough the wall

RareRare

RareRare

Rare,but transmural Rare,but transmural fissuresfissures

(+)(+)

(+) (+)

10-30 years10-30 years

at recto-segmoid at recto-segmoid proximally proximally

Non granulom. Non granulom.

Absent Absent

Mainly mucosalMainly mucosal

CommonCommon

CommonCommon

Common ,and Common ,and pseudo-polypspseudo-polyps

(+++)(+++)

(+++) (+++)

Diverticular disease of colonDefinition :- 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 flatulence3-Infection (diverticulitis ) perforated intestine peritonitis

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 circulation4-Hepatorenal syndrome :- renal failure caused by liver failure 5-Jaundice:- due to liver damage6-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

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

Portal hypertensionDefinition :- 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.

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 cholecystoscopyManifestations 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 stone4-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 .

III-Chronic diffuse glomerulonephritisIII-Chronic diffuse glomerulonephritis ((endend stage kidney):-stage kidney):-DefinitionDefinition :- End pool of many different renal :- End pool of many different renal diseases ,characterized by chronic inflammatiodiseases ,characterized by chronic inflammatio-n of the glomeruli. -n of the glomeruli. Etiology :-Etiology :- 1-It may arises as chronic Gnitis from the start 1-It may arises as chronic Gnitis from the start ((de novo)de novo)2-Associated with other chronic diseases 2-Associated with other chronic diseases as as chronic hypertension and D.M chronic hypertension and D.M Clinical presentation ;-Clinical presentation ;- 1-It may be 1-It may be asymptomatic asymptomatic . . 2-Presented by 2-Presented by proteinuria and hematuria proteinuria and hematuria . . 3-It ended by 3-It ended by renal failurerenal failure. . Manifestations of glomerulonephritis :-Manifestations of glomerulonephritis :-1-Proteinuria1-Proteinuria :- Passage of protein ( albumin ):- Passage of protein ( albumin ) in urinein urine2-hematuria:2-hematuria:- - Passage of blood in urine.Passage of blood in urine.3-Oligouria3-Oligouria : :- Decreased urine volume output- Decreased urine volume outputDue to renal insufficiency and renal failureDue to renal insufficiency and renal failure4-Hypertension4-Hypertension :-Due to activation of renin – :-Due to activation of renin –angiotensin system (ischemia) angiotensin system (ischemia)

TreatmentTreatment :- :- 1-Antibiotic therapy1-Antibiotic therapy ;- In ;- In

casescasesof infection of infection 2-Immunosuppressive 2-Immunosuppressive

drugsdrugs :- In :- In cases with autoimmune cases with autoimmune

destructiondestruction of glomeruli of glomeruli 3-Management of 3-Management of

complicationscomplications :- :- As :-As :-1-Edema 1-Edema 2-Electrolyte imbalance 2-Electrolyte imbalance 3-Systemic hypertension .3-Systemic hypertension .

II- Urinary tract infectionsII- Urinary tract infectionsManifestationsManifestations :- :- 1-1-DysuriaDysuria :- :- Painful passage of urine .Painful passage of urine .2-Urgency and increased frequency 2-Urgency and increased frequency of urination .of urination .3-Cystitis3-Cystitis (inflammation of urinary bladder) (inflammation of urinary bladder)4-Pyelonephritis 4-Pyelonephritis (pyelitis =inflammation of renal pelvis)(nephritis(pyelitis =inflammation of renal pelvis)(nephritis =inflammation of interstitial tissue of the kidney )(pyelonephritis=inflammation of interstitial tissue of the kidney )(pyelonephritis =inflammation of the kidney either acute or chronic =inflammation of the kidney either acute or chronic Scarring andScarring and possible loss of kidney functionspossible loss of kidney functions5-Fever5-Fever & &rigorsrigors associated with associated with pyouria pyouria (presence of pus cells in urine)(presence of pus cells in urine)6-Bilateral renal pain 6-Bilateral renal pain (flank or lion pain)(flank or lion pain)6-Recurrent 6-Recurrent U.T infections U.T infections may refers to presence of U.T obstruction or may refers to presence of U.T obstruction or

urine refluxurine reflux..

III-Renal calculi (renal stones)III-Renal calculi (renal stones)-In any part of the kidney even pelvis or calyces-In any part of the kidney even pelvis or calyces-Composed mainly of -Composed mainly of calcium salts ,uric acid calcium salts ,uric acid ,phosphate and cystein ,phosphate and cystein Predisposing factorsPredisposing factors :- :- 1-U.T infection 1-U.T infection stone formation stone formation U.T U.T

infection again.infection again.2-Change of urine pH 2-Change of urine pH ,predispose for preci-,predispose for preci-pitation of urinary salts .pitation of urinary salts .3-↓Urine volume 3-↓Urine volume concentrate salts.concentrate salts.4-Excess salt secretion 4-Excess salt secretion which increase saltswhich increase salts precipitations (as urates or ca .oxalate). precipitations (as urates or ca .oxalate). 5-U.T obstruction 5-U.T obstruction and and urine stasis urine stasis infection infection and salts precipitationsand salts precipitations6-Bilharzial infestation 6-Bilharzial infestation bilharzial ova act as abilharzial ova act as a nucleus of stone formation nucleus of stone formation Manifestations Manifestations :-:-1-May be 1-May be asymptomaticasymptomatic unless the stone obstructs unless the stone obstructs the kidney structures .the kidney structures .2-Small stone2-Small stoneRenal colic Renal colic and severe pain and severe pain 3-Large stone 3-Large stone Urinary retention .Urinary retention .4-Infection ,fever & chills and pyouria 4-Infection ,fever & chills and pyouria 5-Hematuria5-Hematuria 5-G.I.T symptoms 5-G.I.T symptoms (nausea and vomiting )(nausea and vomiting )7-Damage of renal structures 7-Damage of renal structures renal failure.renal failure.

Diagnosis of renal calculi Diagnosis of renal calculi 1-Measurement of stone -forming 1-Measurement of stone -forming substances in blood and urine substances in blood and urine 2-Detection of stones by X- rays2-Detection of stones by X- rays( or I.V.Pilography or ultrasono-( or I.V.Pilography or ultrasono-graphy (US)graphy (US)TreatmentTreatment :- :-1-1-Preventive measuresPreventive measures asas

1-Increase fluid intake 1-Increase fluid intake 2-Change urine pH 2-Change urine pH 3-Reduction of serum uric acid.3-Reduction of serum uric acid.

2-Surgical2-Surgical :-removal of stones :-removal of stones3-3-LithotripsyLithotripsy--Ultrasonic destru-Ultrasonic destru-ction of stones ,and the fragmentedction of stones ,and the fragmented stones will pass with urine .stones will pass with urine .

VI- Renal failure (R.F)VI- Renal failure (R.F)

DefinitionDefinition :- :- A significant loss of renal function in A significant loss of renal function in both kidneys both kidneys to the point where to the point where GFRGFR is lowered to is lowered to less than less than 10-20%10-20% of normal . of normal .

Types :-Types :-

1-Acute renal failure1-Acute renal failure :- A rapidly progressing loss of :- A rapidly progressing loss of renal function . renal function .

2-Chronic renal failure2-Chronic renal failure :-Slow progressing loss of :-Slow progressing loss of renal function over a number of years renal function over a number of years

Acute renal failureAcute renal failure :-:-Sudden ↓in renal function ,due to Sudden ↓in renal function ,due to pre-renal pre-renal intra-renal or post-renal intra-renal or post-renal causes . It is a causes . It is a reversible process until renal damage occurs.reversible process until renal damage occurs.Causes Causes :-:-Pre-renal causesPre-renal causes Impaired renal blood flow in cases of Impaired renal blood flow in cases of shockshock ,hypertension , sepsis and anaphylaxis ,hypertension , sepsis and anaphylaxis ,perman-,perman-ent renal damage will occur unless blood flowent renal damage will occur unless blood flow and hypoxia are corrected .and hypoxia are corrected .2-Intra-renal causes2-Intra-renal causesa-Acute damage to renal structuresa-Acute damage to renal structuresb-Acute glomerulonephritis b-Acute glomerulonephritis c-Acute pyelonephritis c-Acute pyelonephritis d-Acute tubular necrosis (d-Acute tubular necrosis (ATNATN) by toxins ) by toxins solvents ,drugs and heavy metals ,the mostsolvents ,drugs and heavy metals ,the most common cause of acute renal failure.common cause of acute renal failure.3-Post-renal causes3-Post-renal causes Conditions that block urine outflow by :-Conditions that block urine outflow by :-calculi ,tumors ,prostatic hypertrophy calculi ,tumors ,prostatic hypertrophy renal renal failure.failure.

Manifestations :-Manifestations :- 1-Oliguria (reduced urine output)1-Oliguria (reduced urine output)2-Edema and fluid retention 2-Edema and fluid retention 3-Elevated blood urea nitrogen and 3-Elevated blood urea nitrogen and

serum creatinine (Azotemia)serum creatinine (Azotemia)4-Disturbances in serum electrolytes .4-Disturbances in serum electrolytes .Treatment Treatment :-:- Preventive measures Preventive measures through :-through :-1-Support of blood pressure and blood1-Support of blood pressure and blood volumevolume2-Correction of fluid and electrolytes2-Correction of fluid and electrolytes imbalancesimbalances3-Renal dialysis 3-Renal dialysis 4-Low protein and high CHO in diet to4-Low protein and high CHO in diet to reduce nitrogenous wastesreduce nitrogenous wastes

Chronic renal failureChronic renal failureIt is the end result of many progressive kidney diseasesIt is the end result of many progressive kidney diseasesCausesCauses :- :-

11-Chronic glomerulonephritis-Chronic glomerulonephritis22-Chronic pyelonephritis -Chronic pyelonephritis 33-Obstructive uropathy-Obstructive uropathy44-D.M-D.M55-Hypertension -Hypertension 66-Exposure to chemical toxins or nephrotoxic drugs as aminoglycoside and -Exposure to chemical toxins or nephrotoxic drugs as aminoglycoside and antibiotics (as streptomoycin ,gentamycin and kanamycin ) mostly inantibiotics (as streptomoycin ,gentamycin and kanamycin ) mostly in elder patients with renal insufficiency .elder patients with renal insufficiency .77-Atherosclerosis of the renal artery (-Atherosclerosis of the renal artery (nephrosclerosisnephrosclerosis))

Stages of chronic renal failureStages of chronic renal failure Stage 1Stage 1 :-Diminished renal reserve :-Diminished renal reserve GFR decreased to GFR decreased to 35-50%35-50% of of normalnormalStage 2Stage 2:- Renal insufficiency :- Renal insufficiency GFR decreased to GFR decreased to 20-35%20-35% of normal of normal Stage 3Stage 3 :- Renal failure :- Renal failure GFR decreased to GFR decreased to < 20% < 20% of normal of normal Stage 4Stage 4:-End stage renal failure :-End stage renal failure GFR is less than GFR is less than 5%5% of normal of normal

ManifestationsManifestations :- Renal failure is a multi-system disease ,it has different bad effects on body :- Renal failure is a multi-system disease ,it has different bad effects on body systemssystems

SystemSystem EffectEffectCauseCause

Body fluidsBody fluids

HematologicHematologic

Cardiovascular Cardiovascular

G.I.TG.I.T

Neurologic Neurologic

Musculo-skeletal Musculo-skeletal

1-Polyuria1-Polyuria

2-Metabolic acidosis 2-Metabolic acidosis Abnormal levels of Abnormal levels of Na+,K+, Ca2+,pO4—Na+,K+, Ca2+,pO4—

Anemia ,excess bleeding Anemia ,excess bleeding

––Hypertension &edema-Hypertension &edema-Anorexia, nausea Anorexia, nausea

Uremic encephalopathy –Uremic encephalopathy –

Muscle and bone weakness Muscle and bone weakness ((renal osteodystrophyrenal osteodystrophy))

Inability to concentrate Inability to concentrate urine. urine.

Reduced H+ excretion Reduced H+ excretion caused by loss of tubular caused by loss of tubular function function

Impaired erythropoietinImpaired erythropoietin

Activation of R.A.SActivation of R.A.S

Accumulation of metabolic Accumulation of metabolic wasteswastes

Accumulation of ammonia Accumulation of ammonia and nitrogenous wastesand nitrogenous wastes

Loss of calcium and Loss of calcium and minerals.minerals.

Treatment :-Treatment :-

1-Careful management of fluids and electrolytes. 2-Careful use of diuretics.3-Restriction of protein and increase CHO consumption in diet.4-Giving erythropoietin to treat anemia. 5-Hemodialysis. 6-Renal transplantation .