(1,2) introduction of pathophysiology+ cell injury copy

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(1,2) introduction of pathophysiology+ cell injury copy

  1. 1. بسم الله الرحمن الرحيم <ul><li>Introduction </li></ul><ul><li>Of pathophysiology </li></ul><ul><li>Prof Dr : Yehia El-Alfy </li></ul>
  2. 2. <ul><li>BIOPSY : The use of the diseased tissue or cells for diagnostic purposes . </li></ul><ul><li>I-Tissue : </li></ul><ul><li>1-Tru-cut needle biopsy : is carried out with a wide needle introduced in the suspected area to bring a core of tissue (e.g. liver and breast). </li></ul><ul><li>2-Incision biopsy : It means sampling of a portion of the diseased tissue (Punch biopsy) from a mass in lips,skin, nose…..ect). </li></ul><ul><li>3-Excision biopsy : The entire diseased tissue is completely removed surgically, </li></ul><ul><li>4- Whole diseased organ : as breast and its lymph nodes. </li></ul><ul><li>II- Cells : Cytological examination are obtained as follow: </li></ul><ul><li>1-Aspirated body fluids as ascitis, pleural effusion and C.S.F. </li></ul><ul><li>2-Exfoliated cells in sputum, urine, stools, vaginal and buccal smears. </li></ul><ul><li>3-Fine needle aspiration (FNA) : is the use of a fine needle to bring cells for cytological examination. </li></ul>
  3. 3. <ul><li>Growth disorders </li></ul><ul><li>and </li></ul><ul><li>Adaptation </li></ul>
  4. 4. Disorders of growth and adaptatuin <ul><li>( 1)Increased cellular growth : </li></ul><ul><li> - Hyperplasia. </li></ul><ul><li> - Hypertrophy. </li></ul><ul><li>(2)Decreased cellular growth : </li></ul><ul><li> -Agenesis. </li></ul><ul><li> -Atrophy. </li></ul><ul><li>(3)Abnormal cellular Differentiation : </li></ul><ul><li> -Metaplasia. </li></ul><ul><li> -Dysplasia. </li></ul><ul><li>(4)Abnormal purposeless uncontrolled cell growth: </li></ul><ul><li> - Neoplasia . </li></ul><ul><li>* Enumerate the disorders of growth and discuss one of them in details ? </li></ul>
  5. 5. Increased Growth <ul><li>* 1- Hypertrophy </li></ul><ul><li>- Definition : Increase in the size and weight of organs and tissues due to increase in the size of their constituent cells </li></ul><ul><li>- Types : </li></ul><ul><li>1-Physiological hypertrophy </li></ul><ul><li>(A) Uterine muscles in pregnancy. </li></ul><ul><li>(B) Skeletal muscles in asthelets . </li></ul><ul><li>2-Pathological hypertrophy </li></ul><ul><li>A- Adaptive hypertrophy : </li></ul><ul><li>As in hollow muscular organs after a chronic partial obstruction. e.g. </li></ul><ul><li>* Hypertrophy of urinary bladder due to prostatic enlargement, </li></ul><ul><li>* Hypertrophy of the stomach in pyloric stenosis . </li></ul><ul><li>* Hypertrophy of Left ventricle in case of hypertension. </li></ul><ul><li>B- Compensatory hypertrophy : </li></ul><ul><li>* Best seen in paired organs e.g. after nephrectomy, the other kidney enlarge in size due to hypertrophy. </li></ul>
  6. 6. <ul><li>* </li></ul><ul><li>* 2-Hyperplasia </li></ul><ul><li>* Definition : Increase in the size of an organ or tissue due to increase in the number of its constituent cells . </li></ul><ul><li>* Types: </li></ul><ul><li>1- Physiological hyperplasia : </li></ul><ul><li>e.g.hyperplasia of the breast at puberty and during pregnancy and lactation. </li></ul><ul><li>2- Pathological hyperplasia : </li></ul><ul><ul><li>Compensatory hyperplasia : e.g. formation of regenerating nodules in liver cirrhosis. </li></ul></ul><ul><ul><li>Hormonal hyperplasia : e.g. gynecomastia is marked enlargement of male breast in adults or due to administration of estrogen in cases of cancer prostate. </li></ul></ul><ul><ul><li>Irritation hyperplasia : e.g. hyperplasia of lymphoid tissue in infections . </li></ul></ul><ul><li>- Hyperplasia of the covering epithelium : -After chronic irritation or ulceration in mouth, GIT and respiratory tract </li></ul><ul><li>* Prognosis: </li></ul><ul><li>Hyperplasia occurs in response to a specific stimulus , when it is removed , the tissue tends to convert to its normal size. Thus it differs from neoplasia in this respect. </li></ul>
  7. 7. Differentiation between hyperplasia and neoplasia <ul><li>In Hyperplasia : cells are of normal size and shape, may have a useful function and stops proliferation on removal of the stimulus. </li></ul><ul><li>In neoplasia : # # # # # </li></ul>
  8. 8. Diminished growth <ul><li>Developmental: </li></ul><ul><li>(1) Agenesis : complete failure of development. </li></ul><ul><li>(2) Hypoplasia : failure of development to full mature size. </li></ul><ul><li>Acquired : </li></ul><ul><li>(1) Aplasia : acquired extreme hypoplasia after the organ reaches its full maturation, e.g bone marrow. </li></ul><ul><li>(2) Atrophy : decrease in size and weight of organs or tissues due to reduction in size or number of its constituent cells. </li></ul>
  9. 9. Atrophy <ul><li>Definition : D ecrease in size and weight of organs or tissues due to reduction in size or number of its constituent cells. </li></ul><ul><li>Types : </li></ul><ul><li>( 1)Physiologic Atrophy : ( due to loss of physiologic function) </li></ul><ul><li> 1 - Uterus after delivery. </li></ul><ul><li> 2- Breasts after lactation. </li></ul><ul><li> 3- Gonads after menopause . </li></ul><ul><li>( 2)Pathologic atrophy : </li></ul><ul><li>1-Generalized Atrophy : </li></ul><ul><li>(1)Starvation atrophy : i n anorexia, malignant cachexia . </li></ul><ul><li>(2)Senile atrophy : due to atherosclerotic narrowing of the arteries. </li></ul><ul><li>(3)Toxic atrophy : in chronic wasting diseases as cancers, TB and diabetes. </li></ul><ul><li>(4)Endocrine atrophy : as in hypopiuitarism. </li></ul>
  10. 10. 2-Localized atrophy <ul><li>(1) Ischemic atrophy : gradual vascular obstruction --> cerebral atheroma. </li></ul><ul><li>(2) Pressure atrophy : pressure --> progressive occlusion of bl. V. as </li></ul><ul><li>-atrophy of vertebrae in syphilitic aortic aneurysm. </li></ul><ul><li>-brain atrophy in meningioma. </li></ul><ul><li>-Kidney atrophy in hypernephroma. </li></ul><ul><li>-livercell atrophy in amyloidosis. </li></ul><ul><li>(3) Disuse atrophy : muscle atrophy in casted leg. </li></ul><ul><li>(4) Neuropathic atrophy : paralysed muscles in poliomyelitis. </li></ul><ul><li>(5) Endocrine astrophy : breast atrophy after oopharectomy. </li></ul><ul><li>) 6) Idiopathic atrophy </li></ul>
  11. 11. Abnormalities in cell differentiation <ul><li>1-Metaplasia </li></ul><ul><li>Definition .: It is change of one type of differentiated tissue to another type of the same class of tissue . </li></ul><ul><li>Causes: 1 -Chronic irritation. 2- Chronic infection. </li></ul><ul><li> 3 -Deficiency of certain factors as Vit. A </li></ul><ul><li>Types: </li></ul><ul><li>(1) Epithelial metaplasia. (2) Connective tissue metaplasia. </li></ul><ul><li>(3) Mesothelial metaplasia. (4) Tumor metaplasia. </li></ul><ul><li>Epithelial metaplasia </li></ul><ul><li>(1)Columnar epithelium into squamous epithelium </li></ul><ul><li>-in chronic cholecystitis with stones . </li></ul><ul><li>(2)Transitional epithelium into squamous epithelium </li></ul><ul><li>-in urinary bladder with bilharziasis. </li></ul><ul><li>(3) Pseudostratified columnar ciliated to squamous : </li></ul><ul><li>- In chronic bronchitis with smoking and infection. </li></ul>
  12. 12. 2-Dysplasia <ul><li>Definition : It is a disordered cellular proliferation. </li></ul><ul><li>Characters of dysplastic cells : </li></ul><ul><li>-Pleomorphism (Variation in size and shape(. </li></ul><ul><li>-Loss of polarity (orientation) </li></ul><ul><li>-Hyperchromatic nuclei ( deep basophilic staining). </li></ul><ul><li>-Presence of mitosis. </li></ul><ul><li>* Usually associated with chronic irritation . </li></ul><ul><li>Fate : Although it is potentially reversible it is a premalignant lesion that can progress into cancer. </li></ul><ul><li>Grading of dysplasia </li></ul><ul><li>* Grade I dysplasia taking lower 1/3 of the thickness of cells. </li></ul><ul><li>* Grade II dysplasia taking lower 2/3 of the thickness of cells. </li></ul><ul><li>* Grade III dysplasia taking the whole thickness of cells. </li></ul>
  13. 13. Examples of dysplasia <ul><li>1- Dysplasia of the urinary bladder with bilharziasis. </li></ul><ul><li>2-Dysplasia in uterine cervix with chronic cervicitis </li></ul><ul><li>3-Dysplasia in gall bladder with chronic cholecystitis. </li></ul><ul><li>4-Dysplasia in bronchial epithelium with ch.bronchitis. </li></ul><ul><li>5-Dysplasia in the oral cavity in dental caries. </li></ul>
  14. 14. Cell Injury <ul><li>Definition : Metabolic and Morphological changes in the cells , may be reversible (injury not enough to damage nuclei and cause cell death), or irreversible ( cell death). </li></ul><ul><li>Types: </li></ul><ul><li>1-Reversible : Caused by mild injury and can be reversed by repair mechanisms </li></ul><ul><li>2-Irreversible : Caused by severe injury which results in cell death by one of two mechanisms : a- necrosis (cells simply die) </li></ul><ul><li>b- apoptosis (programmed cell death ) </li></ul><ul><li>Causes of Cell Injury </li></ul><ul><li>(1)Hypoxia : decrease of bl. supply </li></ul><ul><li>(2)Physical : mechanical trauma, burn.electric. </li></ul><ul><li>(3)Chemicals : drugs, Strong acids or alkalines,smoke,heavy metals . </li></ul><ul><li>(4)Microbiologic : Bacteria,viruses, parasitres … </li></ul><ul><li>( 5)Immunologic Reactions </li></ul><ul><li>(6)Radiation : ionizing rad.,x-rays, microwaves . </li></ul><ul><li>(7)Nutritional : malnutrition, obesity . </li></ul>
  15. 15. <ul><li>Mechanisms of cell injury : </li></ul><ul><li>It depends on the type of injury, its duration, and severity , Cell type, state, and adaptability are also responsible. </li></ul><ul><li>These mechanisms include : </li></ul><ul><li>1-ATP depletion : </li></ul><ul><li>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 oxidative phosphorylation of ADP. </li></ul><ul><li>2-Free radical damage (Oxygen derived free radicals ) : </li></ul><ul><li>*Source : are generated as products of normal cell metabolism ( in many oxidative processes in the cells as a products of mitochondrial respiration ) </li></ul><ul><li>* Free Radical Injury Contributes To : </li></ul><ul><ul><li>Chemical and radiation injury </li></ul></ul><ul><ul><li>Oxygen and other gaseous toxicity </li></ul></ul><ul><ul><li>Cellular aging </li></ul></ul><ul><ul><li>Microbial killing by phagocytic cells </li></ul></ul><ul><ul><li>Inflammatory damage </li></ul></ul><ul><ul><li>Tumor destruction by macrophages </li></ul></ul><ul><ul><li>Others </li></ul></ul>
  16. 16. <ul><li>* Examples : as superoxide, hydrogen peroxide, hydroxyl ions and nitric acid .and inactivated by some body enzymes as: catalase and glutathione peroxidase. </li></ul><ul><ul><li>Exogenous sources of free radicals include tobacco smoke, pollutants, radiation, … </li></ul></ul><ul><ul><li>Free radical injury has a key role in the normal aging process, beside a number of diseases as diabetes mellitus, AS, cancer, Alzheimer’s dis., and RH. Arthritis . </li></ul></ul><ul><li>* Free Radical Cell Injury Mechanism: </li></ul><ul><li>1- Damage of membrane lipids. 2- Damage of cellular proteins. </li></ul><ul><li>3- Mutation of cellular DNA. </li></ul><ul><li>3- Disturbance of intracellular calcium : Ischemia and some toxins cause early increase in cytoplasmic calcium by increase Ca influx across the plasma membrane and release of Ca from mitochondria  It activates enzymes causing cell damaging as, phospholipases, proteases . </li></ul><ul><li>4- Defects in membrane permeability : </li></ul><ul><li>It's a feature of all forms of cell injury . It is due to either direct damage of cell membrane e.g. bacterial toxins or ATP depletion . </li></ul><ul><li>5- Mitochondrial damage : </li></ul><ul><li>Mitochondria are targets for all types of injurious stimuli e.g. hypoxia and oxidative stress. Damage is reversible in early stages but if the injurious agent persists, it becomes irreversible leading to cell death through disturbance of oxidative phosphorylation </li></ul>
  17. 17. <ul><li>General morphological changes in cell injury : </li></ul><ul><li>A- Nuclear changes: </li></ul><ul><li>Consist of clumping of chromatin and smaller but more numerous nucleoli with loss of their granular component, which indicates impaired synthesis of ribosomal material . Detected by light microscopy . </li></ul><ul><li>B- Cytoplasmic changes: </li></ul><ul><li>1- Evidence of hyperfunction : Increase the number and complexity of cell organelles. </li></ul><ul><li>2- Evidence of hypofunction : loss of ribosomes leading to impaired protein synthesis. Mitochondria are swollen with icreased calcium content  decrease oxidative phosphorylation. </li></ul><ul><li>3- Evidence of altered function : e.g. cilia may develop in cells not normally ciliated (cells of olfactory mucosa). </li></ul><ul><li>4- Abnormal accumulation of substances in the cells: e.g. lipids. </li></ul><ul><li>5- Degenerative changes : Focal cytoplasmic degeneration and autophagocytic vacuoles are increased in number. </li></ul>
  18. 18. <ul><li>1-REVERSIBLE CELL INJURY </li></ul><ul><li>Definition : It is reversible morphological changes that affect cells. they include : </li></ul><ul><li>I)- Changes associated with disturbance of water metabolism </li></ul><ul><li>a- Cloudy swelling </li></ul><ul><li>It is a reversible cell damage characterized by accumulation of water inside the cells (cellular edema) .It is due to mitochondrial injury </li></ul><ul><li>b -Hydropic (vacuolar) degeneration </li></ul><ul><li>- It is closely related to cloudy swelling but there is  marked increase in the permeability of the cell membrane to water inside the cell, which appears either in the form of multiple small droplets or as a single large vacuole which distends the cells. </li></ul><ul><li>* It may occur in epidermal cells in burns, liver cells in virus hepatitis, islets of Langerhans in some cases of diabetes. </li></ul>
  19. 19. <ul><li>II)- Changes associated with disturbances of fat metabolism </li></ul><ul><li>a- Fatty change (steatosis) </li></ul><ul><li>It means abnormal accumulation of neutral fat (Triglycerides) within parenchymal cells mainly liver, and includes: </li></ul><ul><li>1-Fatty degeneration : (Damaged cells can not metabolize lipids ) </li></ul><ul><li>2-Fatty infiltration: (Increase of fat entry to the cells). </li></ul><ul><li>Pathogenesis of fatty change in the liver : </li></ul><ul><li>1-Excessive starvation  mobilization of fat to liver from fat stores. </li></ul><ul><li>2-Viral hepatitis : Diseased liver cells can not metabolize normal reaching fat to the liver. </li></ul><ul><li>3- Defeciency of lipotropic factors as choline and methionine. which transform neutral fat to a form most of the body cells can utilize it. </li></ul>
  20. 20. 2- Irreversible cell injury (Cell death) <ul><li>Types of cell death : 1- Apoptosis. 2- Necrosis . </li></ul><ul><li>1- APOPTOSIS: </li></ul><ul><li>Definition : It is a programmed ( controlled) cell death occurs with aging and normal wear and tear of the cell </li></ul><ul><li>Apoptosis may be a mechanism to eliminate damaged cells . Certain viruses as (Epstein Barr virus) may activate apoptosis within an infected cell, thus killing both the host cell and infecting virus . </li></ul><ul><li>Apoptosis may involve the activation of certain ( suicide genes) which in response to certain chemical signals activate and lead to cell lysis and destruction . </li></ul><ul><li>It has been theorized that cancer may arise as a failure of normal apoptosis in damaged or mutated cells . </li></ul><ul><li>Types of apoptosis: </li></ul><ul><li>(1) Physiological apoptosis : </li></ul><ul><li>Hormone-dependent involution, such as endometrial breakdown during the menstrual cycle. </li></ul>
  21. 21. <ul><li>(2) Pathological apoptosis : </li></ul><ul><li>- Cell death produced by a variety of injurious stimuli as radiation, and cytotoxic anticancer drugs damage DNA, and if repair mechanisms cannot cope with the injury, the cell kill itself by apoptosis. </li></ul><ul><li>- Cell injury in certain viral diseases as viral hepatitis. </li></ul><ul><li>* Fate of apoptosis </li></ul><ul><li>Phagocytosis of apoptotic cells or cell bodies by macrophages. The adjacent healthy cells migrate or proliferate to replace the space occupied by the apoptotic cell. The plasma membranes remain intact during apoptosis, until the last stages, then it become permeable to normally retained solutes. </li></ul><ul><li>2- NECROSIS </li></ul><ul><li>* Definition : It is local death of small or large groups of cells in a living tissue. </li></ul><ul><li>* Causes: </li></ul><ul><li>1- Cut of blood supply </li></ul><ul><li>2- Trauma 3- Bacterial toxins </li></ul><ul><li>4- Physical and chemical agents </li></ul><ul><li>5- Hypersensitivity reactions </li></ul>
  22. 22. <ul><li>Types of necrosis </li></ul><ul><li>1- Coagulative necrosis : </li></ul><ul><li>- It is due to cut of blood supply by thrombosis and embolism. </li></ul><ul><li>2- Liquefactive necrosis : </li></ul><ul><li>-AS in pyogenic abscess, amoebic abscess and CNS infections. </li></ul><ul><li>3- Caseous necrosis : </li></ul><ul><li>- AS in T.B. infection. The term caseous is derived from the cheesy white appearance of the necrotic area. </li></ul><ul><li>4- Fat necrosis : </li></ul><ul><li>- It describes focal areas of fat destruction, typically occurring as a result of acute pancreatitis due to release of activated pancreatic enzymes into the substance of the pancreas or the peritoneal cavity. The enzymes liquefy fat cell membranes, and split the triglyceride esters. </li></ul>
  23. 23. Cells of inflammation <ul><li>* 1- Polymorphnuclear leucocytes (PNLs) or (microphages): They phagocytose bacteria and necrotic tissue. </li></ul><ul><li>*2- Macrophages : derived from blood monocytes and tissue histiocytes: a- Attack bacteria with fatty sheath as T.B. as they contain enzyme lipase. </li></ul><ul><li>b- Phagocytose necrotic tissue. </li></ul><ul><li>C-Formation of giant cells . </li></ul><ul><li>*3- Eosinophils : in allergic and parasitic inflammation. </li></ul><ul><li>*4- Lymphocytes : Give rise to plasma cells. </li></ul><ul><li>*5 - Plasma cells : form antibodies. </li></ul><ul><li>*6- Foreign body giant cells : formed by fusion several macrophages and phagocytose foreign bodies. </li></ul>
  24. 24. 5 Cardinal Signs of Inflammation <ul><li>1-Redness <- vasodilatation and Hyperaemia. </li></ul><ul><li>2- Hotness <– Increased blood flow and Hyperaemia. </li></ul><ul><li>3-Pain <– irritation of nerve endings by products of inflammation and pressure by inflammatory exudate. </li></ul><ul><li>4-Swelling <– Inflammatory Exudate +vasodilatation. </li></ul><ul><li>5-Loss of Function  due to pain and tissue damage. </li></ul>
  25. 25. <ul><li>Varieties of acute inflammation </li></ul><ul><li>A- Non-suppurative inflammations :- </li></ul><ul><li>1. Catarrhal inflammation as: Rhinitis. </li></ul><ul><li>2. Fibrinous inflammation as : Lobar pneumonia . </li></ul><ul><li>3. Serous inflammation : as: Burns . </li></ul><ul><li>4. Serofibrinous inflammation as: PPP </li></ul><ul><li>5. Membranous inflammation as: Diphtheria. </li></ul><ul><li>6. Allergic inflammation as: Urticaria . </li></ul><ul><li>7. Hemorrhagic inflammation as: In betahaemolytic Strep.infection </li></ul><ul><li>8. Necrotizing inflammation.as : gangrene. </li></ul><ul><li>B- Suppurative inflammations :- </li></ul><ul><li>1-Localized (abscess, boil, carbuncle) </li></ul><ul><li>2-Diffuse (cellulitis) </li></ul>
  26. 26. Healing by 2 nd intention Healing by 1 st intention The 2 ends are non approximated The 2 ends are approximated Infected wound Clean wound Necrotic tissue is found No necrotic tissue No tissue depris Tissue depris Long time to be healed Short time to be healed Much larger scar Small scar Granulation tissue is the first Epithelial growth is the first
  27. 27. <ul><li>Cytokines </li></ul><ul><li>Definition : Soluble proteins secreted by lymphocytes (lymphokines ), monocytes-macrophages (monokines) . </li></ul><ul><ul><li>-Act as effector molecules affecting the behavior of B cells, T cells, NK cells, monocytes, macrophages, and other cell types . </li></ul></ul><ul><ul><li>Examples : Interleukins &quot;1 to 8&quot;, Interferons &quot;(IFN-α), (IFN-β), (IFN-γ)&quot; and Tumor necrosis factors &quot;(TNF-α), (TNF-β ). </li></ul></ul><ul><ul><li>Lymphokines </li></ul></ul><ul><li>- A soluble proteins secreted by lymphocytes. </li></ul><ul><li>1. Chemotactic factors : </li></ul><ul><li>- Attracts neutrophils and macrophages. </li></ul><ul><li>2. Migration inhibition factor (MIF): </li></ul><ul><li>- Helps in granuloma formation. </li></ul><ul><li>3. Mitogenic factor : </li></ul><ul><li>- Stim.mitoses of lymphocytes </li></ul>
  28. 28. <ul><li>4. Cytotoxic factor : </li></ul><ul><li>- Destroying cells, causing caseous necrosis of epithelioid cells of T.B. </li></ul><ul><li>5. Transfer factor : </li></ul><ul><li>- Transfer sensitization to new lymphocytes. </li></ul><ul><li>6. Interferon : antiviral. </li></ul><ul><li>Interferons </li></ul><ul><li>Proteins usually produced by virally infected cells </li></ul><ul><li>* Types of interferons : </li></ul><ul><li>1- Alpha interferon : Secreted by macrophages </li></ul><ul><li>Induced by viruses or polynucleotide. </li></ul><ul><li>2- Beta interferon: Secreted by fibroblasts, viruses, </li></ul><ul><li>3- Gamma interferon: secreted by T- lymphocytes and specific antigens </li></ul><ul><li>* Protective action of interferons : </li></ul><ul><li>1) Activate T-cells </li></ul><ul><li>2) Activate macrophages </li></ul><ul><li>3) Activate NK </li></ul>
  29. 29. Risk Groups <ul><li>1. Homosexual males (60%) </li></ul><ul><li>2. Intravenous drug abusers (24%) </li></ul><ul><li>3. Hemophiliacs (1%) </li></ul><ul><li>4. Other blood recipients (2%) </li></ul><ul><li>5. Heterosexual partners of other high-risk group members </li></ul><ul><li>6. children of parents from groups 1.-3. </li></ul><ul><li>. </li></ul>
  30. 30. 3 Clinical stages of HIV (1) Acute phase stage: (2)Asymptomatic stage(Latent phase) (3) Symptomatic or (AIDS stage) - 2-4 weeks after infection. - Symptoms of acute illness.(Fever,fatigue …) -Transient reduction of CD8+, CD4+ number. -Symptoms disappear later  asymptomatic - Long period 5-10 years) free of infection symptoms. - Slow persistent destruction of immune cells  decrease number of circulating CD4+ lymphocytes and CD8+ lymphocytes - Marked decrease in CD4+ lymphocytes -AIDS-related complex (ARC): fever, night sweats, diarrhea and * opportunistic infections 1- Tumors: Kaposi' sarcoma 2- Neurologic: dementia complex Loss of memory ,
  31. 31. <ul><li>Malignant </li></ul><ul><li>Not well cirumscribed, </li></ul><ul><li>Usually larger in size, </li></ul><ul><li>Fast growing, </li></ul><ul><li>non capsulated, </li></ul><ul><li>Invasive & Infiltrate </li></ul><ul><li>Hge and necrosis. </li></ul><ul><li>Metastasize. </li></ul><ul><li>poorly differentiated, </li></ul><ul><li>Suffix “Carcinoma” or “Sarcoma” </li></ul><ul><li>Benign </li></ul><ul><li>Well circumscribed, </li></ul><ul><li>Usually small in size, </li></ul><ul><li>Slow growing, </li></ul><ul><li>capsulated, </li></ul><ul><li>Non-invasive </li></ul><ul><li>No hge. and necrosis </li></ul><ul><li>do not metastasize, </li></ul><ul><li>well differentiated, </li></ul><ul><li>suffix “oma” eg. Fibroma. </li></ul>
  32. 32. Signs of malignancy <ul><li>Cellular </li></ul><ul><li>Dysplasia (different from tissue of origin) </li></ul><ul><li>Disorganization </li></ul><ul><li>Loss of polarity. </li></ul><ul><li>Pleomorphism (variable in size and shape) </li></ul><ul><li>Loss of cohesion. </li></ul><ul><li>Presence of giant cells </li></ul><ul><li>Nuclear </li></ul><ul><li>Large nuclei </li></ul><ul><li>Hyperchromasia. </li></ul><ul><li>N/C ratio high. </li></ul><ul><li>Pleomorphic nuclei. </li></ul><ul><li>Prominent nucleoli. </li></ul><ul><li>Frequent mitoses. </li></ul><ul><li>Abnormal mitotic figures. </li></ul>Functional: Loss of normal function of the cell
  33. 33. Spread of malignant tumours Local (Direct) spread : - Aided by loss of cell cohesion . - Along lines of least resistance . Distant spread : 1- Lymphatic spread: -Lymphatic embolism . Groups of cell travel through lymphatics to regional L.Ns. -Lymphatic permeation . Tumors cells grow within lymphatics as solid cords. 2- Blood spread: 3- Transcoelomic spread: peritoneal cavity, plleura, pericardium, ventricular system of the brain.
  34. 34. What is a “Tumor Marker”? <ul><li>A tumor marker is a substance present in or produced by a tumor or by the tumor’s host in response to the tumor’s presence </li></ul><ul><li>It can be used: • to differentiate a tumor from normal tissue or • to determine the presence of a tumor. </li></ul><ul><li>Such a substance can be found in: • cells • tissues • body fluids </li></ul><ul><li>It can be measured qualitatively or quantitatively by: • chemical • immunological • molecular biological methods </li></ul>
  35. 35. Types of Tumor Markers <ul><li>Cellular (tissue tumor markers): detected in tissues . </li></ul><ul><li>Humoral (present in blood and body fluids: </li></ul><ul><ul><li>Hormones (hCG; calcitonin; gastrin; prolactin; growth hormone, etc.) </li></ul></ul><ul><ul><li>Enzymes (acid phosphatase; alkaline phosphatase; PSA) </li></ul></ul><ul><ul><li>Proteins & Glycoproteins (CA 125; CA 15.3; CA 19.9, etc.) </li></ul></ul><ul><ul><li>Oncofetal antigens (CEA, AFP) </li></ul></ul><ul><ul><li>Receptors (ER, PR, EGFR) </li></ul></ul><ul><ul><li>Oncogenes (Ras; Myc; abl-bcr) </li></ul></ul><ul><ul><li>Tumor suppressor genes (BRCA1; p53; Rb) </li></ul></ul>
  36. 36. Characteristics of the “Ideal” Tumor Marker <ul><li>1-Measured easily, reliable, and cost-effectively </li></ul><ul><li>2-High sensitivity </li></ul><ul><li>3-High specificity. </li></ul><ul><li>4-Organ specificity.( PSA for prostate…….) </li></ul><ul><li>5-Correlated with tumor stage. </li></ul><ul><li>6-Corelated with prognosis </li></ul>
  37. 37. Clinical Uses of Tumor Markers • Screening for cancer (Alfa feto protein for liver cancer) • Diagnosing cancer – (pelvic mass) • Evaluating prognosis of cancer- (CEA in colon cancer) • Tumor staging - • Detecting Tumor Recurrence or remission - • Localizing tumor and directing chemo- or radio-therapeutic agents- • Monitoring the effectiveness of cancer therapy
  38. 38. Hormones of the Pituitary (A) Hormones of anterior pituitary 1- Growth hormone (GH). Stimulates growth of long bones, organs and muscle during development 2- Adrenocorticotrophic hormone (ACTH). Stimulates the adrenal cortex to produce adrenal hormones such as cortisol 3- Thyroid-stimulating hormone (TSH). Regulates secretion of thyroid hormones T 3 and T 4
  39. 39. <ul><li>4- Luteinizing hormone (LH). </li></ul><ul><li>Stimulates testosterone production and induction of ovulation ( secretory function of the corpus luteum) . </li></ul><ul><li>5- Follicle-stimulating hormone (FSH) . </li></ul><ul><li>Help spermatogenesis and maturation of ova. </li></ul><ul><li>6- Prolactin (PRL). </li></ul><ul><li>- Initiates and maintains milk production in the mammary glands postpartum. </li></ul>
  40. 40. (B) Hormones of the posterior pituitary <ul><li>1- (Oxytocin) : </li></ul><ul><li>On uterus :  Stimulates contraction of uterine smooth muscle during labor. </li></ul><ul><li>On breast :  stim. milk ejection from the mammary glands </li></ul><ul><li>2- Antidiuretic hormone (ADH , vasopressin ) - Stimulate water reabsorption in the collecting ducts of the kidney. </li></ul>
  41. 41. Hypopituitarism: *-Decreased activity of the pituitary gland due to hyposecretion of one or more pituitary hormones. - If all pit.hs. are lacking,  panhypopituitarism . *-Manifestations are highly variable and depend on the hormone or hormones that are lacking . Etiology : Pituitary damage due to: 1- Trauma. 2- Infection. 3- Ischemia. 4- Tumors.
  42. 42. Disorders of the anterior pit. gland Growth hormone hyposecretion Manifestations  In children :  short stature ( dwarfism ).  In adults :  Muscle weakness and obesity . Treatment: GH replacement therapy
  43. 43. Growth hormone hypersecretion 1- Gigantism  results from the excess production of GH before fusion of the epiphyseal plates of the long bones (around puberty). * Manifestations : Extremely tall stature due to excessive growth of the long bones . 2- Acromegaly  GH excess occurs after fusion of the epiphyseal plates of the long bones . * Manifestations : Overgrowth of C.T. , Bones grow more in width than in length  patients presented with thickening and deformation of the hands, face, skull and feets. 3- C.N.S. disturbances (headache, vision changes). 4- C.V.S. disease: As(hypertension , coronary artery disease). Treatment Surgical removal of tumor. Radiation therapy of the tumor if surgery is not feasible .
  44. 44. Disorders of the posterior pituitary A- Increased Production of ADH . - Caused by pituitary tumors or injury or transiently due to physiologic stress. Manifestations  Excessive fluid retention  Generalized oedema (Weight gain).  Incrased in serum sodium level. Treatment  Fluid restriction.  Diuretics.  Removal of tumor if present
  45. 45. <ul><li>Diabetes insipidus </li></ul><ul><li>B- Decreased production of ADH . </li></ul><ul><li>Etiology : Decreased ADH is due to defects in the hypothalamus/ pituitary axis or from a tumor or trauma . </li></ul><ul><li>Manifestations </li></ul><ul><li> Polyuria : E xcessive production of very dilute urine. </li></ul><ul><li>Polydypsia : Excessive thirst. </li></ul><ul><li> Dehydration : Increased plasma osmolarity. </li></ul><ul><li>Hypo tension and reflex tachycardia. </li></ul><ul><li>Treatment </li></ul><ul><li>* Administration of ADH and ADH analogues like lypressin and desmopressin </li></ul><ul><li>* ADH itself is administered by S.C. or I.M. injection, whereas lypressin and desmopressin are administered as an intranasal spray. </li></ul><ul><li>* An oral form of desmopressin is also now available. </li></ul>
  46. 47. Alterations of thyroid function <ul><li>Hypothyroidism. </li></ul><ul><li>1- Primary condition : </li></ul><ul><li>Resulting from a defect within the thyroid gland itself ( surgical removal, infection, tumour , radiation…..) </li></ul><ul><li>2- Secondary : </li></ul><ul><li>1-Due to defect in hypothalamus or pituitary gland </li></ul><ul><li>2-Dietary deficiency of iodine  hypertrophy of the thyroid gland that presents as a goiter </li></ul>
  47. 48. <ul><li>Manifestations of hypothyroidism : </li></ul><ul><li>1-In fetal life ( Cretinism). </li></ul><ul><li>2-In adults ( Myxedema). </li></ul><ul><ul><li>1- Cretinism </li></ul></ul><ul><ul><li>Occurs during fetal development as a result of congenital defect in thyroid development and characterized by  </li></ul></ul><ul><li>Poor overall development and growth retardation.as  </li></ul><ul><li>* Serious retardation of mental and physical development (dwarf, thick,flabby waxy skin,flat nose, protruded tongue ,pot-belly abdomen,loss of teeth and hair,umbilical hernia) </li></ul>
  48. 49. <ul><li>2-Myxedema </li></ul><ul><li>Hypothyroidism in the adult </li></ul><ul><li>May result from autoimmune destruction of the thyroid or thyroid injury or removal. </li></ul><ul><li>Presents with signs of hypometabolism including: </li></ul><ul><li>Cold intolerance, Weight gain, Fatigue, Bradycardia, Cool, dry skin, Anorexia, Constipation, Edema of the face (swelling around the eyes), hands and ankles; drooping eyelids </li></ul><ul><li>* These changes are reversible with thyroid hormone therapy </li></ul><ul><li>Treatment </li></ul><ul><li>Thyroid hormone replacement therapy. </li></ul><ul><li>A variety of synthetic and natural T3 /T4 preparations are available for use orally. </li></ul>
  49. 50. Hyperthyroidism - It is hyperfunction of the thyroid gland due to over secretion of thyroid hormones. Causes : 1- Primary hyperthyroidism : Overactive gland ( Grave’s dis . Or secondary toxic goiter or functioning adenoma or carcinoma). 2- Secondary hyperthyroidism : a- Excessive stim. of thyroid by excess TSH (Pit.Tum.) or b-By tumour outside thyroid gland that produce thyroid hormones or TSH ( paraneoplastic syndromes)
  50. 51. Grave's disease <ul><li>Definition : It is autoimmune disease that considered as one of the most common causes of hyperthyroidism . </li></ul><ul><li>Mechanism : Autoantibodies that bind TSH receptors on the thyroid and mimic the actions of TSH  excess production of thyroid hormones. </li></ul><ul><li>Manifestations </li></ul><ul><li>1-Increased basal metabolic rate  Increased heat production, patient always feels &quot; hot&quot;, Tachycardia, Increased catecholamine sensitivity; patients are at risk for cardiac arrhythmias, Increased appetite, Weight loss, Enhanced bowel activity  diarrhea . </li></ul><ul><li>2- Nervousness , excitability and bad dreams . </li></ul>
  51. 52. <ul><li>Treatment </li></ul><ul><li>1-Antithyroid drugs (propyl-thiouracil, carbimazole  block production of thyroid hormones. </li></ul><ul><li>2-Beta -Blockers drugs to blunt the effects of excess adrenergic stimulation. </li></ul><ul><li>3-Radioiodine : It is given orally. </li></ul><ul><li>4-Surgical ablation of a portion of the thyroid ( partial thyroidectomy). </li></ul>
  52. 53. Diabetes mellitus Risk Factors for Diabetes Mellitus 1 . Obesity. 2.Familial history of diabetes mellitus. 3.Increasing age. 4.Dietary factors.
  53. 54. Types of diabetes mellitus Type I diabetes (insulin-dependent diabetes ).  Due to progressive autoimmune destruction of the pancreatic  cells, idiopathic, or following viral infections.  'Little or no insulin secretion occurs . Manifestations: 1-Hyperglycemia. 2- Weight loss. 3-The three &quot;polys“. - Polydypsia, (increased thirst), - Polyphagia (increased appetite), - Polyuria (increased urine output )
  54. 55. <ul><li>4- Weakness and fatigue: </li></ul><ul><li>* Due to poor energy utilization and skeletal muscle catabolism </li></ul><ul><li>5-Diabetic ketoacidosis : </li></ul><ul><li>* Accumulation of acidic ketone bodies in the blood due to a lack of insulin-stimulated fatty acid utilization ). </li></ul><ul><li>Treatment </li></ul><ul><li> Insulin replacement therapy </li></ul><ul><li> Dietary management </li></ul>
  55. 56. Type II diabetes mellitus (non-insulin-dependent diabetes) 1- More than type I diabetes. 2 -Unknown cause. 3-There is &quot;insulin resistance,&quot; (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
  56. 57. Mechanisms of Tissue Injury in Chronic Diabetes Mellitus 1- Glycosylation of proteins : Attachment of glucose to proteins in the eye, blood vessel walls, and kidney membranes  change their structure  altered function and eventual damage of these tissues 2- Formation of alcohol sugars (example: sorbitol )  do not easily diffuse out of tissues  swelling and damage of tissues. 3- Poor blood flow and oxygen delivery to tissues :  reduce overall blood flow to tissues  ischemic injury.
  57. 58. Long-term complications of diabetes mellitus 1. Diabetic neuropathy : is due to ischaemia . 1-Abnormality of nerve conduction and function, affects peripheral nerves. 2-Numbness, pain or sensory /motor impairment. 2. Diabetic nephropathy  Thickening of the glomerular basement membrane and glomerulosclerosis due to trrapping of Glycosylated protein in the glomeruli  Glomerular filtration decreases  albuminuria
  58. 59. 3 . Vascular disease 1-Coronary artery disease, cerebrovascualr disease and peripheral vascular injury due to:elevated serum lipid levels,enhanced atherogenesis (formation of athero-sclerotic leions). 2-Peripheral vascular disease  gangrene and amputations (particularly of the toes and feet). 4.Impaired healing and increased infections risk due to poor blood flow -  limits the delivery of leukocytes and oxygen to the injured area  ) impairing removal of debris and infectious organisms.  The high glucose levels serve as a nutrient to support the growth of microorganisms .
  59. 60. <ul><li>5. Diabetic retinopaathy </li></ul><ul><li>1- Retinal damage due chronic hvpoxemia, </li></ul><ul><li>2-Hemorrhage of eye capillaries and chronic inflammation  increases in intraocular pressure that scar the retina and impair vision  blindness. </li></ul><ul><li>3-Diabetes is also associated with an increased incidence of glucoma and cataract formation. </li></ul>
  60. 61. A- Genetic Defects 1-Hemophilia: Caused by a genetic deficiency or lack of certain clotting factors . Type A hemophilia :  Most common form (80% or more).  X-linked recessive disorder Results from a deficiency of clotting factor VIII (8). Type B hemophilia (Christmas disease):  Second most common form of hemophilia (10 to 15%)  X-linked autosomal recessive disorder.  Results from a deficiency of clotting factor IX (9) Type C hemophilia (Rosenthal's disease):  Least common of all hemophilia cases (<5%).  Results from a deficiency of clotting factor XI (11).  Autosomal recessive disorder.
  61. 62. Manifestations of hemophilia  May present as a-mild, moderate or severe bleeding disorder depending on the activity of the clotting factors  Excessive bleeding with trauma or surgery.  Bleeding into soft tissues, muscles and joints. Treatment of hemophilia  Avoidance of injury, prevention of bleeding.  Replacement with recombinant clotting factors.
  62. 63. *Gastro-esophageal reflux Definition :- Backflow of gastric contents into the esophagus Cause : - 1-It results from weakness or incompetence of the cardiac sphincter 2-It may be caused by a hiatus hernia Manifestations :- 1-Burning sensation at gastric region ( heart burn )aggravated by alcohol ,caffeine ,smoking and lying down. 2-Esophagitis and esophageal ulceration 3-Dysphagia and poor nutrition 4-Chronic esophagitis and possibility of esophageal cancer. Complication:- It leads to irritation and inflammation  ulceration of lower end of esophagus by its acidic contents.
  63. 64. Treatment: - Medical treatment 1-Eating of small frequent meals 2-Sleeping with elevated head 3-Consumption of fluids with foods 4-Use of anti-acids or proton pump inhibitors to reduce gastric acidity Surgical treatment Surgical correction of the present hiatus hernia .
  64. 65. Peptic ulcers Definition:- It is mucosal loss of any part in G.I.T. Mucosal loss of gastric mucosa  called gastric ulcer. Causes :- 1-Infection with Helicobacter pylori (in 80-95% of cases) ,that damage the protective mechanisms of the G.I.T . 2-Stressful conditions 3-Damage of mucus secreting cells 4-Excessive acid production in the stomach (increase gastrin hormone  increase acid secretion )( Zollinger – Ellison syndrome ) 5-Chronic use of aspirins and NSAIDS Complications :- 1-Hemorrhage :- Hematemesis and melena . 2-Gastric perforation :- Leading to peritonitis. 3-Fibrosis : Obstruction of duodenum and hour glass deformity of the stomach . 4-Malignant transformation :- 1-2% of cases  gastric carcinoma
  65. 66. Manifestations of peptic ulcer disease :- 1-Attacks of remission and exacerbation 2-Pain is relieved by eating(doudenal ulcer) ,or by anti-acids( gastric ulcer) 3-G.I.T bleeding (hematemesis&melena) (20-25% of cases) 4-Perforation of ulcer  ↑ mortality rate 5-G.I.T obstruction (fibrosis) Treatment of peptic ulcer :- 1-Avoidance of alcohol ,smoking and NSAIDS 2-Antibiotic therapy for H.P 3-Anticholinergic and antiacids 4-H2 receptors antagonists (proton -bump inhibitors) 5-Mucosal protective measures 6-Resection of tumor in pancreas
  66. 67. Crohn`s disease :- Definition :- Chronic transmural (affecting all layers of terminal ileum and colon  terminal ileitis),non-caseating granulomatous inflammatory reaction , charact-erized by skip lesions. Etiology :- 1-Idiopathic 2-Auto-immune disease 3-Post- infection ,mediated by inflammatory cytokines Pathology :- -The disease is commonly found in certain populations as in Jews , U.S ,Western Europe and Scandinavia in 20-40 years,with intermittent attacks of remission and exacerbation . -The disease can affects any region of G.I.T,but it is commonly seen in distal ileum and colon at ileocecal valve. -It form a transmural granulomatous inflammation of the affected parts,with distinctive cobble stone appearance to the mucosa -Areas of inflammations are separated by non inflammed (skip) areas .
  67. 68. Manifestations : - 1-Anorexia ,nausea and vomiting 2-Fever 3-Bloody diarrhea. 4-Abdominal pain 5-Loss of weight from malabsorption 6-Fibrosis and intestinal obstruction 7-Abdominal fistula ,between colon and abdominal wall Treatment :- 1-Nutritional support and total parenteral nutrition in severe cases. 2-Anti-inflammatory drugs 3-Blocking the action of cytokines by drugs or antibodies.  
  68. 69. Ulcerative colitis Definition :- Chronic ulcero-inflammatory diseases affects the distal colon (rectum and colon) and extends backward (back-wash ileitis) Etiology :- 1-Idiopathic 2-Genetic or immunologic disorders Pathology :- 1-The disease affects individuals between 10-30 years especially who has family history of the disease with attacks of remission and exacerbation 2-The disease is commonly found in mucosa with continuous fashion (no skip areas) . Manifestations:- 1-Fever & abdominal pain 2-Chronic bloody diarrhea. 3-Weight loss and anemia 4-The possibility of perforated intestine ,blood loss and cancer colon.
  69. 70. Treatment :- 1-Nutritional support 2-Surgical resection of the diseased part to reduce incidence of cancer 3-Anti-inflammatory drugs and salicylates to suppress inflammation. 4-Sulfasalazine drug (sulfa and aminosalicylate) 5-Nicotine exerts a protective effect in ulcerative colitis .
  70. 71. U.colitis Crohn`s disease Item 10-30 years at recto-segmoid  proximally Non granulom. Absent Mainly mucosal Common Common Common ,and pseudo-polyps (+++) (+++) 20-40 years Any part of GIT at ileo-cecal region Granulomatous inflamm. present Through the wall Rare Rare Rare,but transmural fissures (+) (+) Age of onset Location Inflammation Skip lesions Layers involved Bloody stool Malabsorption Ulcers Crypt abscesses Propensity for malignancy
  71. 72. Diverticular disease of colon Definition :- Multiple sac-like protrusions of the intestinal wall . Types :- a-True diverticula :- Involves all layers of the intestinal wall B-False diverticula :- Involves only the mucosa . Etiology :- 1-In elder patients with chronic constipation 2-In individuals who consume a low fiber diet (chronic constipation) 3-Any condition that increase intraluminal pressure (constipation ) with weakened wall especially at sites of penetration of nutrient arteries or due to congenital weakeness in bowel wall . Manifestations :- Treatment : - 1-Increased bulk of diet and its fiber content 2-Antibiotics for diverticulitis 1-Asymptomatic 2-Changes in bowel habits and flatulence 3-Infection (diverticulitis )  perforated intestine  peritonitis
  72. 73. Manifestations of alcohol cirrhosis :- 1-Hepatosplenomegaly :- enlarged sizes of liver and spleen . 2-Ascites :- Caused by portal hypertension and hypoalbuminemia 3-Portal hypertension :-Increased blood pressure in portal circulation 4-Hepatorenal syndrome :- renal failure caused by liver failure 5-Jaundice:- due to liver damage 6-Hepatic encephalopathy :- Caused by accumulation of ammonia and other toxins in circulation  by pass hepatic detoxication  can reach the brain  Neurological dysfunction . 7-Esophageal varices :- Ruptured ,distended veins at lower end of the esophagus  hematemesis . Distended abdominal veins around umbilicus is called  caput medusa and in rectum  Piles 8-Reduced metabolism of sex hormones :- Hyperestrogenemia  gynecomastia in male,menstrual irregularities in females and abnormal sexual function of both ( loss of libido ) 9-Liver failure
  73. 74. 8-Reduced metabolism of sex hormones :- Hyperestrogenemia  gynecomastia in male,menstrual irregularities in females and abnormal sexual function of both ( loss of libido ) 9-Liver failure
  74. 75. Portal hypertension Definition :- Elevated blood pressure in portal circulation Causes : due to pre-hepatic ,hepatic and post – hepatic obstructive causes . Effects :- 1-The increased portal pressure causes stagnation of blood in spleen (splenomegaly) 2-The collateral blood vessels of the abdomen and esophagus are dilated forming varices. Symptoms :- 1-Bleeding of varices 2-Hepato-splenomegaly 3-Possibility of pancytopenia ( due to hypersplenism ) 4-Ascites due to portal hypertension and hypoalbuminemia Treatment of cirrhosis:-. 1-Nutritional supplementation with vitamins and reduction of protein diet to decrease ammonia 2-Diuretics to relieve fluid retention 3-Shunting operation to relieve bleeding from accessory collaterals 4-Management of symptoms of liver failure.
  75. 76. Gall stone formation (cholelithiasis) Bile composed of water,bile salts ,cholesterol and bilirubin -Gall stones are hardened precipitate of bile that predominantly contain cholesterol -Their sizes varies . - Contributors of gall stone formation -Gall stones may be detected by radiography ,ultrasonography and cholecystoscopy Manifestations of gall stones. 1-Nausea ,vomiting ,fever and chills . 2-Acute and severe biliary colic ( in small migratory stone) 3-A large sized stone  obstructs bile ducts  Jaundice . Treatment :- 1-Preventive measures;- low fat diet 2-Surgical treatment:-Cholecystectomy (surgically removed G.B.) 3-Endoscopic removal of the stone 4-Lithotripsy :- Breakdown of the stone by sound waves -Aging and sex (common in females) -Excess cholesterol or bilirubin -Obesity -Sudden dietary changes or abnormal fat metabolism .
  76. 77. <ul><li>III-Chronic diffuse glomerulonephritis ( end </li></ul><ul><li>stage kidney):- </li></ul><ul><li>Definition :- End pool of many different renal </li></ul><ul><li>diseases ,characterized by chronic inflammatio </li></ul><ul><li>-n of the glomeruli. </li></ul><ul><li>Etiology :- </li></ul><ul><li>1-It may arises as chronic Gnitis from the start </li></ul><ul><li>( de novo) </li></ul><ul><li>2-Associated with other chronic diseases as </li></ul><ul><li>chronic hypertension and D.M </li></ul><ul><li>Clinical presentation ;- </li></ul><ul><li>1-It may be asymptomatic . </li></ul><ul><li>2-Presented by proteinuria and hematuria . </li></ul><ul><li>3-It ended by renal failure . </li></ul><ul><li>Manifestations of glomerulonephritis :- </li></ul><ul><li>1-Proteinuria :- Passage of protein ( albumin ) </li></ul><ul><li>in urine </li></ul><ul><li>2-hematuria: - Passage of blood in urine. </li></ul><ul><li>3-Oligouria : - Decreased urine volume output </li></ul><ul><li>Due to renal insufficiency and renal failure </li></ul><ul><li>4-Hypertension :-Due to activation of renin – </li></ul><ul><li>angiotensin system (ischemia) </li></ul><ul><li>Treatment :- </li></ul><ul><li>1-Antibiotic therapy ;- In cases </li></ul><ul><li>of infection </li></ul><ul><li>2-Immunosuppressive drugs :- In </li></ul><ul><li>cases with autoimmune destruction </li></ul><ul><li>of glomeruli </li></ul><ul><li>3-Management of complications :- </li></ul><ul><li>As :- </li></ul><ul><li>1-Edema </li></ul><ul><li>2-Electrolyte imbalance </li></ul><ul><li>3-Systemic hypertension . </li></ul>
  77. 78. <ul><li>II- Urinary tract infections </li></ul><ul><li>Manifestations :- </li></ul><ul><li>1- Dysuria :- Painful passage of urine . </li></ul><ul><li>2-Urgency and increased frequency of urination . </li></ul><ul><li>3-Cystitis (inflammation of urinary bladder) </li></ul><ul><li>4-Pyelonephritis (pyelitis =inflammation of renal pelvis)(nephritis </li></ul><ul><li>=inflammation of interstitial tissue of the kidney )(pyelonephritis </li></ul><ul><li>=inflammation of the kidney either acute or chronic  Scarring and </li></ul><ul><li>possible loss of kidney functions </li></ul><ul><li>5-Fever & rigors associated with pyouria (presence of pus cells in urine) </li></ul><ul><li>6-Bilateral renal pain (flank or lion pain) </li></ul><ul><li>6-Recurrent U.T infections may refers to presence of U.T obstruction or urine reflux </li></ul><ul><li>. </li></ul>
  78. 79. <ul><li>III-Renal calculi (renal stones) </li></ul><ul><li>-In any part of the kidney even pelvis or calyces </li></ul><ul><li>-Composed mainly of calcium salts ,uric acid </li></ul><ul><li>,phosphate and cystein </li></ul><ul><li>Predisposing factors :- </li></ul><ul><li>1-U.T infection  stone formation  U.T infection again. </li></ul><ul><li>2-Change of urine pH ,predispose for preci- </li></ul><ul><li>pitation of urinary salts . </li></ul><ul><li>3-↓Urine volume  concentrate salts. </li></ul><ul><li>4-Excess salt secretion which increase salts </li></ul><ul><li>precipitations (as urates or ca .oxalate). </li></ul><ul><li>5-U.T obstruction and urine stasis  infection </li></ul><ul><li>and salts precipitations </li></ul><ul><li>6-Bilharzial infestation  bilharzial ova act as a </li></ul><ul><li>nucleus of stone formation </li></ul><ul><li>Manifestations :- </li></ul><ul><li>1-May be asymptomatic unless the stone obstructs </li></ul><ul><li>the kidney structures . </li></ul><ul><li>2-Small stone  Renal colic and severe pain </li></ul><ul><li>3-Large stone  Urinary retention . </li></ul><ul><li>4-Infection ,fever & chills and pyouria </li></ul><ul><li>5-Hematuria </li></ul><ul><li>5-G.I.T symptoms (nausea and vomiting ) </li></ul><ul><li>7-Damage of renal structures  renal failure. </li></ul><ul><li>Diagnosis of renal calculi </li></ul><ul><li>1-Measurement of stone -forming </li></ul><ul><li>substances in blood and urine </li></ul><ul><li>2-Detection of stones by X- rays </li></ul><ul><li>( or I.V.Pilography or ultrasono- </li></ul><ul><li>graphy (US) </li></ul><ul><li>Treatment :- </li></ul><ul><li>1- Preventive measures as </li></ul><ul><ul><li>1-Increase fluid intake </li></ul></ul><ul><ul><li>2-Change urine pH </li></ul></ul><ul><ul><li>3-Reduction of serum uric acid. </li></ul></ul><ul><li>2-Surgical :-removal of stones </li></ul><ul><li>3- Lithotripsy - Ultrasonic destru- </li></ul><ul><li>ction of stones ,and the fragmented </li></ul><ul><li>stones will pass with urine . </li></ul>
  79. 80. <ul><li>VI- Renal failure (R.F) </li></ul><ul><li>Definition :- A significant loss of renal function in both kidneys to the point where GFR is lowered to less than 10-20% of normal . </li></ul><ul><li>Types :- </li></ul><ul><li>1-Acute renal failure :- A rapidly progressing loss of renal function . </li></ul><ul><li>2-Chronic renal failure :-Slow progressing loss of renal function over a number of years </li></ul>
  80. 81. <ul><li>Acute renal failure :- </li></ul><ul><li>Sudden ↓in renal function ,due to pre-renal </li></ul><ul><li>intra-renal or post-renal causes . It is a </li></ul><ul><li>reversible process until renal damage occurs. </li></ul><ul><li>Causes :- </li></ul><ul><li>Pre-renal causes </li></ul><ul><li>Impaired renal blood flow in cases of shock </li></ul><ul><li>,hypertension , sepsis and anaphylaxis ,perman- </li></ul><ul><li>ent renal damage will occur unless blood flow </li></ul><ul><li>and hypoxia are corrected . </li></ul><ul><li>2-Intra-renal causes </li></ul><ul><li>a-Acute damage to renal structures </li></ul><ul><li>b-Acute glomerulonephritis </li></ul><ul><li>c-Acute pyelonephritis </li></ul><ul><li>d-Acute tubular necrosis ( ATN ) by toxins </li></ul><ul><li>solvents ,drugs and heavy metals ,the most </li></ul><ul><li>common cause of acute renal failure. </li></ul><ul><li>3-Post-renal causes </li></ul><ul><li>Conditions that block urine outflow by :- </li></ul><ul><li>calculi ,tumors ,prostatic hypertrophy  renal </li></ul><ul><li>failure. </li></ul><ul><li>Manifestations :- </li></ul><ul><li>1-Oliguria (reduced urine output) </li></ul><ul><li>2-Edema and fluid retention </li></ul><ul><li>3-Elevated blood urea nitrogen and serum creatinine (Azotemia) </li></ul><ul><li>4-Disturbances in serum electrolytes . </li></ul><ul><li>Treatment :- </li></ul><ul><li>Preventive measures through :- </li></ul><ul><li>1-Support of blood pressure and blood </li></ul><ul><li>volume </li></ul><ul><li>2-Correction of fluid and electrolytes </li></ul><ul><li>imbalances </li></ul><ul><li>3-Renal dialysis </li></ul><ul><li>4-Low protein and high CHO in diet to </li></ul><ul><li>reduce nitrogenous wastes </li></ul>
  81. 82. <ul><li>Chronic renal failure </li></ul><ul><li>It is the end result of many progressive kidney diseases </li></ul><ul><li>Causes :- </li></ul><ul><ul><li>1 -Chronic glomerulonephritis </li></ul></ul><ul><ul><li>2 -Chronic pyelonephritis </li></ul></ul><ul><ul><li>3 -Obstructive uropathy </li></ul></ul><ul><ul><li>4 -D.M </li></ul></ul><ul><ul><li>5 -Hypertension </li></ul></ul><ul><ul><li>6 -Exposure to chemical toxins or nephrotoxic drugs as aminoglycoside and </li></ul></ul><ul><ul><li>antibiotics (as streptomoycin ,gentamycin and kanamycin ) mostly in </li></ul></ul><ul><ul><li>elder patients with renal insufficiency . </li></ul></ul><ul><ul><li>7 -Atherosclerosis of the renal artery ( nephrosclerosis ) </li></ul></ul><ul><li>Stages of chronic renal failure </li></ul><ul><li>Stage 1 :-Diminished renal reserve  GFR decreased to 35-50% of </li></ul><ul><li>normal </li></ul><ul><li>Stage 2 :- Renal insufficiency  GFR decreased to 20-35% of normal </li></ul><ul><li>Stage 3 :- Renal failure  GFR decreased to < 20% of normal </li></ul><ul><li>Stage 4 :-End stage renal failure  GFR is less than 5% of normal </li></ul>
  82. 83. <ul><li>Manifestations :- Renal failure is a multi-system disease ,it has different bad effects on body systems </li></ul>Cause Effect System Inability to concentrate urine. Reduced H+ excretion caused by loss of tubular function Impaired erythropoietin Activation of R.A.S Accumulation of metabolic wastes Accumulation of ammonia and nitrogenous wastes Loss of calcium and minerals. 1-Polyuria 2-Metabolic acidosis Abnormal levels of Na+,K+, Ca2+,pO4— Anemia ,excess bleeding – Hypertension &edema-Anorexia, nausea Uremic encephalopathy – Muscle and bone weakness ( renal osteodystrophy ) Body fluids Hematologic Cardiovascular G.I.T Neurologic Musculo-skeletal
  83. 84. <ul><li>Treatment :- </li></ul>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 .

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