Jumat, 26 Juni 2009

IRFT VALLEY FEVER

RIFT VALLEY FEVER


PENDAHULUAN


Rift Valley fever adalah penyakit infeksi akut yang ditularkan melalui vektor yang merupakan penyakit viral pada domba dan sapi yang menyebabkan keguguran dan menyebabkan kematian tinggi pada domba muda dan anak sapi. Ciri khasnya yaitu periode ingkubasi yang singkat, demam leukopenia, nekrosi pada hati, dan inklusi asidofilik inti sel hati. Rift Valley Fever merupakan zoonosis yang diasumsikan dapat menyebar dari lembah Rift Kenya ke daerah Dfrika lainnya yang menyebabkan penyakit serius pada manusia dan hewan.

Henning (1952,1956) menjelaskan penyakit yang lainnya di Afrika Utara yang hampir mirip dengan Rift Valley Fever yang disebabkan oleh agen yang dinamkan virus Wesselbron.

Hubungan serologis telah dibuktikan antara Rift Valley Fever dan Zinga virus, yang kemungkinannya adalah strain virus Rift Valley Fever, dan berdasarkan hal ini kedua virus tidak dapat dibedakan.


ETIOLOGI


Virus ini dikategorikan kedalam famili Bunyaviridae yang berdasarkan morfologi dan karakteristik biokimia, dan juga pada cross reaksi serologi dengan virus grup demam phlebotomus. Bentuk virus tersebut spiral, berdiameter 90 sampai 100nm, dan memiliki proyeksi permukaan yang hampir sama yang diemukan pada virus bunyaviridae. Virus dapat tumbuh dengan biakkan sel kultur, kecuali lymphoblastosid sel line, dan pertumbuhannya dapat dilihat dengan menggunakan teknik fluorescent antibody (FAT).

Virus pada famili Bunyaviridae dicirikan dengan adanya RNA rantai tunggal dengan tiga segmen unik, protein nukleokapsid yang berasosiasi dengan RNA, dan amplop yang mengandung minimal satu virus spesifik glikoprotein. Ukuran strain viscerotropik diteliti dan tidak ditemukan perbedaan signifikan dari bentuk neurotropik (Naude et al, 19454)

Pertumbuhan virus Rift Valley Fever pada fibroblast tikus dicirikan dengan 6 jam priode latent, kejadian titer virus dari kedua sel bebas dan sel asosiasi virus adalah selama 16 dan 20 jam, dan fase pelepasan virus lebih kurang selama 48 jam (Johnson dan Orlando 1968).

Teknik Fluorescent Antibody digunakan untuk mendeteksi antigen virus Rift Valley Fever pada kultur jaringan setelah inkubasi selama 5 jam. Pewarnaan fluorescent selalu pada sitoplasma (Easterday dan Jaeger 1963).


EPIZOOTIOLOGY


  1. Distribusi Geografis

Penyakit ini pertama kali dilaporkan di lembah Rift Kenya dan terletak pada daerah Afrika.

Sellers (1981) menjelaskan sebelumnya mengenai kejadian epizootik pada hewan domestik dan epidemik pada manusia di Afrika pada tahun 1979. Beberapa faktor yang mempengaruhi epizootik meliputi iklim, vektor, perpindahan reservoir, dan reservoir hewan domestik.

Epizootik RVF terjadi di Kenya pada tahun 1961 – 1962 ( Coackley et al. 1976a) dan pada tahun 1978-79 (Davies dan Highton 1980). Karena tingginya kejadian aborsi yang diamati selama kejadian penyakit, RVF diduga sebagai penyebabnya (Scott et al 1963).

Davies dan Onyango 1978 mengatakan bahwa kera vervet (Cerophitecus aethiops) kemungkinan bukan sebagai host reservoir virus RVF di Kenya. Sepuluhpersen dari abortus diteliti melalui diagnosis lavoratorium di zimbabwe dalam periode 1 tahun ditemukan sebagai RVF ( Shone et al 1958). Pada tahun 1983 dan 1976 kejadian penyakit RVF dilaporkan di Sudan (Eisa et al 1980).

Hingga tahun 1976-1977, RVF dinyatakan zoonosis dilaporkan hanya di Sub-saharan Afrika, tetapi tahun 1977 kejadian penyakit terjadi di Mesir (Peters dan Meegan 1981).





  1. Penularan


Virus Rift Valley Fever ini ditularkan ke sapi dan domba muda melalui gigitan arthtropoda; nyamuk kemungkinan yang menjadi vektor penting. Infeksi pada manusia disebabkan melalui makanan yang terkontaminasi atau karena material laboratorium.

Virus Rift Valley Fever kemungkinan ditransmisikan secara biologis dan mekanis oleh vektor hematophagos. Meskipun manusia dapat terinfeksi, hampir semua hewan dapat trinfeksi melalui vektor nyamuk (Meegan et al 1980). Rift Valley Fever diisolasi dari Culex Theileri, Aedes linneatopennis, Anopheles coustani, Aedes dentatus, dan Eretmapocites quinquevittatus pada waktu epizootik di Afrika Utara. Hali ini disimpulkan bahwa Culex theileri merupakan vektor penting pada anan sapi dan domba.


GEJALA KLINIS


Sindrom klinis diklasifikasikan atas perakut, akut, subakut, dan ringan . Keparahan dari tanda yang terjadi tergantung pada spesies dan umur Host. Sindrom yang paling parah telah diamati pada anak domba, anak sapi, dan domba dewasa. Gejala utamanya tidak spesifik dan meliputi demam, leleran hidung, dan aborsi. Pada sapi maupun domba, bukti yang menunjukkkan penyakit kemungkinannya adalah aborsi. Angka kematian kemungkinan mencapai 70% pada anak domba dan anak sapi. Pada sapi maupun domb, bukti yang menunjukkan penyakit kemungkinannya adalah aborsi.

Pada manusia, RVF mungkin bermanifestasi pada salah satu seperti penyakit benign yang ditandai dengan demam, sakit kepala dan malaise atau sperti sindrom akut yang disirikan dengan hepatik, sistem saraf pusat, dan komplikasi okular.

Pada domba dewasa, secara acak timbul penyakit akut meliputi vomitting, leleran mukopurulen dari hidung, pulsus cepat, aborsi dan angka kematian 20 sampai 30%. Bentuk subakut juga biasa terjadi pada hewan dewasa dan dicirikan dengan demam, anoreksia, kelmahan umum, dan aborsi. Pada bentuk ringan, hanya trjadi reaksi febrile. Pada domba muda , biasa terjadi dengan bentuk perakut. Sindrom tersebut memiliki periode ingkubasi 12 jam dan menyebabkan kematian lebih bersifat variabel pada kambing dan timbul dalam bentuk kurang parah (Easterday 1965).

Gejala RVF pada anak sapi tidak tentu, penghambatan laktasi, salivasi, diare, dan demam merupaan tanda yang dilaporkan (Easterday 1965).

Rift Valley Fever pada menusia dalam bentuk akut, febrille, sindrom swlf-limiting yang terkadang menyebabkan kematiankaren ademam berdarah. Skit self limiting bukan komplikasi memiliki masa ingkubasi 2 sampai 6 hari (Peters an Meegan 1981). Pada manusia penyakit ini dicirikan dengan demam, sakit kepala, sakit pada otot, lemah, mual, dan malaise dengan rentang waktu 1 sampai 4 hari. Kasus lebih lanjut berhubungan dengan sindrom yang lebih parah meliputi demam berdarah, nekrosis hepatik, enchepalitis dan kopmplikasi okular (Easterday 1965).


PATOLOGI


Virus Rift Valley Fever menyebabkan perubahan patologis yang sama pada tiap hewan domestik dan laboratorium. Sifat pathognomonis dari sindrom ini meliputi nekrosis hepatik focal atau conflluent, inklusi inti sel, dan subkutan, serosal , dan mukosal hemoragis. Encephalittis terjaddi pada hewan laboratorium yang teerinfeksi strain neurotroppik yang dicirkan dengan nekrosis jaringan saraf pertumbuhan inklusi aasidofilik intisel dan gliosis. Lesi okular dengan hemoragis vasulitis, dan retinitis diamati pada beberapa kasus di manusia.

Pada studii sementara mengenai perkembangan lesi pada anak domba secara eksperimental diinfeksikan dengan virus RVF, yang ditemukan warna abu-abu hingga foci biru kekuningan, berdiameter 00,5 hingga 1mmm, terbentuk di parenkim hati dalam waktu 28 dan 40 jam setelah inokulasi. Foci ini memmbesar tiap 12 jam dengan pembesaran 2 sammpai 2,5 mm. Pada lesi-lesi diamati perubahann histolois yng terjadi termasuk degenerasi hepatocyte dan necrosis pembentukan muural thrombii, pembentukan badan inklusi inti sel aidofilik, dan infiltrasi leukocytes dan histiocytes (Easterday1965).

Perubahan pada hati pada domba yang baru lahir berlanjut dari focal, lesi primer, dan necrotik hepatocyes dengann badan asidofilik dalam 6 sampai 12 jam untuk pembesaran foci primer dan degenerasi parenkim dalam 30 sampai 36 jam ( Coetzer dan Ishak 11982)

Kasus fatal yang terjadi pada manusia terjadi pada saat epidemic RVF 1977 di Mesir yaitu nekrosis hati parah,, pneumonia intestnal, dan degeenerasi myokardiaal ( Abdel- Wahabb et al 1978)


VAKSINASI


Vaksin yang disiapkan dari strain neurotropik yang disebarkan melalui serial intraserebral pada mencit tidak cukup memiliki immunogenik dan menyebabkan keguguran ketika dimasukkan ke dalam ewes hamil. Manusia yang divaksinasi dengan virus RVF yang tumbuh pada kultur jaringan dan kemudian diinaktivasi dengan foalin. Pada hewan, injeksi tunggal dengan vaksin yang sama menginduksi titer antibodi netralisasi yang rendah yang tidak selalu mengakibatkan keguguran atau mengakibatkan viremia. Karena itu, multipel injeksi vaksin yang mengandung virus dan adjuvant sangat direkomendasikan. Perkembangan anomalies berhubungan dengan penggunaan vaksin yang digabung virus RVF dengan virus wesselbron; yang nantinya virus tersebut menjadi agen pennyebab.

Vaksin yang diproduksi melalui otak tikus atau melalui embrio telur mengakibatkan aborsi pada ewes bunting dan bersifat immunogenik lemah ( Easterday 1965). Anak sapi yang divaksin RVF strain neurotropik meengakibatkan respon serum antibody nutralizing berlevel rendah, tetapi tetap memiliki derajat immunitas yang sama ketika di bandingkan dengan virus pantropik 28 bulan kemudian. Beberapa anak sapi yang terlahir dari induk yang divaksin memiliki antibodi didalam serumnya yang sebelumnya menyusu dari kolostrum. Serum anak sapi dan domba yang terinfeksi virus pantropik mengadung antibodi level tinggi yang berangsung selama 2,5 dan 3 tahun ( Coackley et al. 1967 a,b).

Vaksin RVF poten aman diterapkan bagi manusia . Vaksin tersebut disiapkan dari rhesus dan kultur sel ginjal monyet hijau Afrika yang diinnfeksikan dengan strain pantropik dan diinaktifkan dengan formalin. Vaksin ini sangat stabil untuk potensi immunogenik dan terbukti efektiff mencegah dari resiko tinggi pekerja laaboratorium ( Radall ett al. 1963, 1964).

Efek dari berbagai dosis dan kombinaasi vaksin hidup dan vaksin mati dapat dilihat pada anak sapi. Respon antibodi pada injeksii pertama dari salah satu vaksin tersebut responnya buruk ketika dipastikan melalui serum virus neutralisasi dan Hemaglutinin Inhibisi test, tetapi dosis pendorong dari vaksin inaktif menghasilkan respon anamnestik yang baik. Anak sapi yang divaksin dengan vaksin hidup tetapi negatif RVF dalam tesst serologis dapat kebal ketika di coba dengan virus RF virulent ( Barnard 1979 ).



DIAGNOSIS


Gejala yang menandakan peyakit terseebut adalah:

  1. Mortalitas tingi pada domba dan sapi

  2. Tingginyaangka aboruuss

  3. Lesi hepatik

Lesi hepatik dan hemorags merupakan tanda diagnostik yang pentng. Beberapa uji yag dipakai untuk tujuan diagnosis yaitu serum netralisasi, Hemaglutinin Inhibisi, dan CF test.


PENCEGAHAN


Rift Vlley Feverdapat dicegah meelaluii vaksinasi pada anak sapi dan omba Vektor penyebab dapat dicegah dengn penggunaan pestisida, insktisida.








Daftar Pustaka.


-Lesos, George.1986. Infectius Tropical Disease Of dometik animal. Churcill Living Stone Innc. Newyork. United States of Amerika

-Henning, M. W.,1952. Rift Valley Fever, J.S. Afr. Vet. Med. Ass, 23 (2); 65-78

-Nande, W. du. T., Madsen,T. and Polsen, A., 194. Difernt – sized infektive particles f Rift Valley Fever virus, Nature. 173: 1051-2

-Soehasono. 2002. Zoonosis Penyakit Menular Dari Hewan Ke Manusia. Kanisius. Jogjakarta.




























test toefl

Test TOEFL


Menulis Ejaan Yang Baik dan Benar


Section 2

YOUR TIME IS

25 Minute


This section is designed to measure your ability to recognize language that is appropriate for standard written English. There are two types of questions in this section, with special directions for each type.


Part A


Direction: In part A each problem consists of an incomplete sentence. Four word or phrases, marked (A), (B), (C), (D), are given beneath each sentence. You are to choose the one word or phrase that best completes the sentence. Then, on your answer sheet, find the number of the problem and mark your answer.


Example 1.


We got a lot of exercise during our holiday in the Swiss Alps………….skiing every day.

(A) to (C) in

(B) by (D) on


Sample answer: A “B” C D (the answer is B)


In English you should read, “ We got a lot of exercise during our holiday in the Swiss Alps by skiing every day.” Therefore, you should choose (B).


Example II.


Los Angeles never gets snowstorms and Honolulu……………

(A) is too (C) isn’t either

(B) does too (D) doesn’t either


The Answer is (D)


The sentence should read, “Los Angeles never gets snowstorms and Honolulu doesn’t either.” Therefore, you should choose (D).









Now try this asshole.


  1. While formerly a member of the sports club, Mr. Teeters………………tennis there regularly.

(A) is used to playing (C) used to play

(B) was used to play (D) used to playing


  1. Some scientists say it is essential that mankind………the amount of air pollution in big cities.

(A) reduce (C) be reduced

(B) reduced (D) will reduce


  1. Having arrived at the football stadium barely in time, ……….

    1. the two teams were just starting as we sat down.

    2. we reached our seats just as the game started.

    3. the officials had already blown the whistle for the game to start.

    4. the gatekeeper took our tickets as we passed.


  1. ……..the rhinoceros is carefully protected, it will soon go the way of other extinct species.

(A) If (C) As long as

(B) Therefore (D) Unless


  1. Most of the courses at the banquet were completely consumed, but there…………food still remaining.

(A) were few (C) were a few

(B) was little (D) was a little

  1. A person probably picks up any language most easily……….it is a child outside a classroom.

(A) learn (C) by learning

(B) to learn (D) for learning


  1. The boy’s father built them a large sandbox………..

(A) to play in (C) to play in there

(B) to play in it (D) in which to play in there


  1. This beach is usually closed………a rainy day.

(A) in (C) at

(B) on (D) while


  1. The movie was very boring and many people began to leave early. By the end, most people…………..

(A) had already left (C) were already left

(B) were already leaving (D) had already been leaving


  1. The little boy first took off one shoe and then took off…………

(A) other (C) the other

(B) another (D) each other


  1. That’s not the butcher we always buy our meat from; you’ve gone to…….one

(A) wrong (C) the wrong

(B) wrong (D) some wrong

  1. After years of great unhappiness in her life, Mrs. Palmer one day just seemed to go…………….

(A) mad (C) madder

(B) madly (D) madness


  1. The police are accusing this businessman of having his store………up so that he could collect the insurance.

(A) blow (C) blew

(B) blown (D) blowing


  1. Hardly ever………get a good job these days without a good education.

(A) people might (C) people can

(B) do people (D) have people


  1. The Joneses’ corn did very well this year, so at harvest time they gave us quite…………

(A) many of them (C) much of it

(B) a few of them (D) a lot of it



Part B


Direction : In questions 16-40 each sentence has four words or phrases underlined. The four underlined parts of the sentence are marked (A), (B), (C), (D). You are to identify the one underlined word or phrase that should be corrected or rewritten. Then, on your answer sheet, find the number of the problem and mark your answer.


Example I.

One of Mrs. Wilson’s (A)daughters (B)doesn’t play the piano as (C)skillful as the other one (D)does.


Answer is (C) , the underlined adjective skillful, would not be accepted in carefully written English. The adverb skillfully should be used instead. Therefore, the sentence should read: “One of Mrs. Wilson daughters doesn’t play piano as skillfully as the other one does.





Example II:

The woman (A)said she (B) had saw the robbery (C)take place (D)on the previous day.


Answer is (B). The form seen should be used after had. Therefore, the sentence should read, “The woman said she had seen the robbery take place on the previous day.” To answer the problem correctly, you would choose (B).


Try this bastard smart ass



  1. Nelson (A)could of won (B)the fight, with a little more (C)training and (D)a better manager.


  1. The cost of (A)fruits and vegetables (B)go up (C)and down partly (D)because of seasonal factors.


  1. Professor Watford (A)asked his students to explain (B)himself more (C)clearly than they (D)had so far done.


  1. It was on the second (A)days of our (B)camping trip (C)that the storm suddenly (D)struck and destroyed much or our equipment.


  1. (A)While in Los Angeles, visitors have the chance to (B)do many interesting things, (C)such as attending concerts and (D)seen Hollywood and Disneyland.


  1. (A)Pedestrians should (B)across this wide boulevard only (C)when they have (D)the green light.


  1. (A)Between Mt. Everest and Mt. Kilimanjaro, (B)the (C)former is the (D)highest.


  1. At the (A)busiest airports, flights are often (B)delayed (C)as result of (D)very heavy traffic.


  1. The policeman found (A)out the burglar hiding in the (B)basement of the (C)jewelry shop while the alarm was (D)still ringing.


  1. (A)It is commonly (B)understand that one kilogram (C)is equal (D)to about 2.2 pounds.


  1. Yugoslavia has been one nation (A)for many years, (B)even though it is composed (C)by people of several (D)different nationalities, languages and religions.


  1. (A)In sport, (B)as in war, the side with the greater (D)strength usually (D)win.


  1. (A)Lack of a certain chemical (B)in the blood of some people makes (C)it is impossible for bleeding to stop in the event of (D)an injury.


  1. (A)When (B)a country’s currency (C)is devalued, imports from abroad then (D)more cost.


  1. In (A)recent years, the (B)best-known Japanese firms (C)have managed to outperform (D)those of the majority of their foreign competitors.


  1. (A)Heart attacks and strokes can be (B)caused by clots that block arteries and (C)resulting in great damage (D)to the heart or brain.


  1. (A)The world War I (B)began (C)in 1914 after Archduke Ferdinand of Austria-Hungary (D)had been assassinated.


  1. Antarctica has (A)so cold temperatures that (B)no one is (C)able to live there (D)permanently.


  1. Human health and (A)the environment must (B)be protected, but many countries emphasize more the need (C)to economic (D)development.


  1. The decision to raise (A)or lower the (B)world price of oil is (C)very up to OPEC; it is really not (D)for other countries to make.


  1. The theory (A)behind foreign aid (B)is that richer countries have (C)an obligation to do something (D)to the poorer ones.


  1. American universities have been cutting (A)their costs (B)by (C)reducing the percentage of full-time teaching positions and increasing the part-time (D)one.


  1. Mrs. Carter and Mrs. Reagan (A)they became (B)well-known for their efforts to (C)deal with serious (D)social problems.


  1. The child received many (A)lovely gifts (B)on her birthday, probably more than (C)it was good (D)for her.


  1. Mrs. Lincoln was (A)sitting (B)besides the President when he was (C)shot (D)at Ford’s Theater in Washington in 1865.

,

The answer would be do correction after the question sent to this blogg.


Kamis, 25 Juni 2009

istilah patologi

1. Apoptosis--programmed cell death. Ugeskr Laeger. 1999 Oct 18;161(42):5778-82.

The health of multicellular organisms depends not only on the body's ability to produce new cells but also on controlled cell death. Apoptosis, or programmed cell death, is the opposite of mitosis. It is an active process for destruction of unwanted and superfluous cells. Changes in cell survival contribute to the pathogenesis of such varied disorders as cancer, many viral infections, neuropathies and immunopathies. The growing understanding of apoptosis forms the basis for development of new therapeutic strategies controlling cell death. This article describes mechanisms involved in the programmed cellular suicide.

Apoptosis is the elimination of unwanted cells with minimum disruption of the surrounding tissue.

This physiological death is caused by the activation of internal mechanism.

Morphologically there is condensation and fragmentation of the chromatin.

Apoptosis occurs in single or small clusters of cells with elimination of unwanted cells during embryogenesis and in various physiological and pathological states.

Separation of apoptotic cells from its adjacent normal cells is caused by fragmentation of its nucleus and cytoplasm and removal by shedding or lysis after phagocytosis.

Example: (i) Healthy adult tissue ; (ii) Embryonic development ; (iii) Malignant tumours - spontaneous or induced regression by therapy ; (iv) Involution and atrophy of tissues and organs.

2. Autolysis

If enzymatic degradation is the dominant element then dead cells are likely to be completely removed.

This process may be accomplished by the activation of enzymes which are normally present within the affected cell.

This process of self-digestion is known as autolysis.

The enzymes are derived largely from lysosomes.

The precise sequence of events leading to the activation and release of lysosomal enzymes is not known, but it is likely that a decrease in the intracellular pH is an important factor.

Release of lysosomal enzymes in cell death can be inferred from the following:

- Ultracentrifugal fractionation of dead cells shows that lysosomal enzymes are no longer particle-bound but appear in the supernatant.

- There is evidence of enzymatic digestion of cell components in the loss of both DNA and RNA protein and glycogen.

3. Caseous necrosis is found characteristically in tuberculosis

It is a form of coagulative necrosis, in that no liquefaction has occurred, but microscopically the affected tissue appears completely structureless, under the microscope and exhibits a greater than usual affinity for acidic dyes such as eosin.

It owes its name (caseous=cheese-like) to its macroscopic appearance, large areas of caseous necrosis bearing some resemblance to white, crumbly goat cheese.

On chemical analysis, large amounts of lipid are found to be present in these necrotic areas in addition to the coagulated protein.

4. cell injury

Cells encounter many stresses as a result of changes in their internal and external environments.

The patterns of response to this stress constitute the cellular basis of disease.

If an injury exceeds the adaptive capacity of the cell, it dies.

Pathology is the study of cell injury and the expression of a pre-existing capacity to adapt to such injury, on the part of either injured or intact cells.

Causes of Cellular Injury:

Diagram showing Structural Changes in Reversible and Irreversible Cell Injury: click here

1. Lack of O2 supply (Hypoxia)- e.g. Ischemia, Cardio-respiratory failure.

2. Loss of O2 carrying capacity of blood as in Anemia, CO poisoning

3. Physical agents - heat, cold, radiation etc. Hypothermia ; Hyperthermia.

4. Chemical agents including - acids, alkali, drugs, insecticides etc.

5. Infections - bacteria, virus, fungus, parasites etc. Infectious Disease Online

6. Immunologic reactions such as autoimmune diseases

7. Genetic disorders: chromosomal alteration or mutation - e.g. Sickle cell disease

8. Nutritional injury [e.g. Protein Calorie Malnutrition (Kwashiorkor), Vitamin A Deficiency causing Xerophthalmia, Keratomalacia and Night blindness].Nutritional Pathology Online

Normal cell contains higher K+ and low Na+ than extra-cellular fluid maintained by Sodium Pump (ATP dependent Cell membrane Transport system).

A cell needs ATP to maintain its normal metabolic functions:

i) Membrane transport system (Failure of Na pump causes swelling of cell).

ii) Protein synthesis (Reduced protein synthesis causes lipid deposition).

iii) Phospholipid turnover (lack of peroxidation causes damage of cell membrane).

Lesions:

Gross features:

The organ involved is pale and increased in weight.

Microscopic features:

Injured cells show cellular swelling due to increased volume of water, sodium and potassium and are characterized by a large, pale cytoplasm and a normally located nucleus called hydropic or vacuolar degeneration. Lipid vacuoles appear later mainly in cells participating in metabolism (e.g. hepatocytes, myocardial cells).

Ultrastructural Structures:

i) Plasma membrane shows alteration, blebbing, blunting or distortion of microvilli and loosening of intercellular attachment.

ii) Mitochondria show swelling and there is appearance of phospholipid-rich amorphous densities.

Reversible cell injury:

These are the pathologic changes that can be reversed when the stimulus is removed or if the cause of injury is mild.

Reversible cell injury is characterized by the cellular swelling with accumulation of fat, protein and other substances e.g. steatosis, cholesterosis, glycogen, and others. If the injury persists the changes become irreversible.

Irreversible cell injury (Cell Death):

Injury to cell causes:

1. Change in mitochondria : Swelling and abnormal cristae.

2. Damage of the plasma membrane causing leakage of soluble enzymes (detected in serum in myocardial injury).

3. Fragmentation of the nuclear membrane.

Cell death: This means the series of morphological changes which occur in relation to a cell or group of cells following lethal injury. It is the element of time and the action of enzymatic degradation and protein denaturation which determine the differences between functional cell death and cell death as morphologically defined.

Two main types:

1. Necrosis

2. Apoptosis

5. coagulative necrosis

In coagulative necrosis, denaturation of intra-cytoplasmic protein is the dominant process.

The dead tissue becomes firm and slightly swollen.

The protein molecules within the cytoplasm becomes unfolded and this renders the tissue both more opaque than normal and more reactive to certain dyes such as eosin.

Microscopically, the cells show the signs of nuclear death , but the most noteworthy feature is the retention of the general architectural pattern of the tissue, despite the death of its constituent elements.

Coagulative necrosis occurs typically in ischemic injury, such as may occur in the heart and kidney.

However, for reasons which are not clear, ischemic injury in the central nervous system leads to necrosis dominated by enzymatic digestion and liquefaction of the dead tissue.

7. fat necrosis

This is almost exclusively seen in the female breast especially, if the breast is heavy and pendulous.

Essentially it results from the rupture of adipocytes with release of their contents.

The released fat undergoes lipolysis and is converted to fatty acids and glycerol.

Clinically the lesion appears as a hard lump in the breast, which may give the impression that a malignant neoplasm is present.

On slicing the excised specimen one may see a small central cystic area in which some oily droplets are present. At the periphery the adipose tissue is much firmer and also more opaque than usual.

Histological examination of conventionally prepared material shows the presence of numerous granular macrophages which contain phagocytosed lipid. Fatty acid crystals are also often present and these excite a foreign body giant cell reaction (multinucleate cells formed as a result of the fusion of macrophages).

8. Gangrene:

Gangrene is characterized by extensive necrosis superadded with putrifaction. Visit: Necrosis

Dry gangrene (mummification):

This is due to arterial obstruction, commonly in old age with atherosclerosis followed by thrombosis of the large and medium size arteries of the limbs, slowly over a long period. Venous drainage is normal. Visit: Hemostasis and Thrombosis

Dry gangrene usually starts in the most distal part of the extremities.

Skin of the affected areas is dry, shrivelled and black like that of mummy due to diffusion of hemoglobin from small vessels into the extra-vascular space (Example: Senile gangrene, diabetic gangrene).

Gangrene extends upwards till it reaches a point where circulation is sufficient to keep the part alive.

This junction of living and dead tissue is called line of demarcation and consists of granulation tissue formed due to irritation of dead tissue.

Granulation tissue erodes the dead tissue finally causing complete detachment (spontaneous amputation).

In younger age, it is seen in thrombo-angiitis-obliterans (Buerger’s disease)- due to inflammatory occlusion of both artery and vein.

Wet Gangrene:

This is due to obstruction of vein with intact arterial supply (Example: strangulated loop of gut in hernia, prolonged application of tourniquet etc).

Gangrene is distal to the site of obstruction.

Marked edema allows rapid growth of bacteria often with gas formation.

Absorption toxin causes profound toxemia.

Gas Gangrene: Gas Gangrene:click here

This is rapidly spreading tissue necrosis, often involving muscle as in crush injury in road accident.

This is due to infection by saccharolytic and proteolytic Clostridia along with other pyogenic bacteria.

This may be rarely seen in suppurative appendicitis, strangulated loop of intestine, puerperium.

Affected muscles and soft tissues are edematous, crepitant on palpation due to gas bubbles in the tissue and commonly develops profound toxemia and septicemia.

Microscopic features of Gangrene:

i) Absence of inflammation.

ii) Cell shrinkage.

iii) Chromatin -condensation and fragmentation.

iv) Cellular blebbing and fragmentation are followed by removal by shedding or phagocytosis by macrophage.

9. Edema:

Diagram showing Capillary System and Mechanisms of Edema Formation

Edema is the increased fluid in the interstitial tissue spaces or body cavities [e.g. hydrothorax, hydropericardium, hydroperitoneum (ascites)] .

Edema may be:

i) Localized due to isolated venous or lymphatic obstruction or

ii) Systemic (generalized)

Severe generalized edema with marked subcutaneous tissue swelling is called anasarca as seen in heart failure.

Causes of edema:

1. Increased capillary permeability.

(disebabkan karena panas yang ekstrim ex : tersiram air panas)

2. Increased capillary hydrostatic pressure.

(Disebabkan panas dalam tubuh yang meningkat, penyakit kekurangan gizi ex: kwarsiokhor)

3. Decreased colloid osmotic pressure of blood plasma (oncotic pressure)

(Disebabkan hipoproteinemia)

4. Lymphatic obstruction

(disebabkan oleh virus hepatitis, parasit yang bermigrasi, tumor)

5. Increased tissue osmotic pressure

6. Retention of Na+ in tissues.

1. Increased capillary permeability:

Normally capillary walls are permeable to water and electrolytes but impermeable to plasma proteins which maintain the colloid osmotic pressure of the blood. When capillaries are damaged by toxic or anoxic causes, it becomes permeable to proteins. Plasma proteins move into tissue space lowering the colloid osmotic pressure of blood and raising that of the tissue. As a result there is escape of more fluids which is retained in the tissue by the protein molecules. Example: Acute inflammation, burns, severe anemia, allergic reactions etc

2. Increased capillary hydrostatic pressure of blood:

- Capillary hydrostatic pressure depends upon venous pressure and not upon arterial pressure. So, when there is obstruction in venous return, capillary hydrostatic pressure rises at both ends of the capillaries, resulting in more output of fluid at arterial end and no absorption at venous end ( more over some fluid may come out at venous end). This causes retention of fluid in tissue leading to edema e.g.

- Congestive cardiac failure

- Constrictive pericarditis

- Cirrhosis of liver

- Venous thrombosis etc

3. Decreased colloid osmotic pressure of blood:

Colloid osmotic pressure of blood is the force that retains fluid in the capillaries against the driving force of capillary hydrostatic pressure. Colloid osmotic pressure of blood depends partly on total amount of plasma proteins and partly on their relative proportion. Colloid osmotic pressure depends upon the number of molecules per unit volume of solution. Hence, of the protein, albumin having the smallest molecular weight exerts greater influence than globulins (albumin exerts 4 times stronger effect than globulins). Loss of proteins particularly albumin results in edema. When total proteins go below 4 gm% or there is loss of albumin with alteration of Albumin : Globulin ratio, from normal 2-3:1 to 1:1, edema will result.

Examples:

Cirrhosis of liver

Severe protein malnutrition as in Kwashiorkor (reduced synthesis),

Protein losing glomerulopathies (Nephrotic syndrome)

Protein losing gastroenteropathies

4. Lymphatic obstruction:

Some of the intercellular fluid is drained out by lymph vessels and any obstruction in its outflow will usually cause local edema e.g.

Filariasis : It often causes massive lymphatic obstruction in inguinal region. This edema extends to external genitalia and lower limbs producing elephantiasis. Long standing edema causes proliferation of connective tissue causing solid edema.

Breast carcinoma: After removal and/or irradiation of breast, there may be severe edema of the arm and the overlying skin may show accentuation of the depression of hair follicles -called “peau d’orange” (orange peel).

5. Increased Tissue Osmotic Pressure:

In acute inflammation there is increased tissue colloid osmotic pressure due to break down of tissue proteins into osmotically active small particles and leakage of serum proteins through damaged capillary walls raising colloid osmotic pressure of tissue.

6. Primary Sodium retention:

Retention of Na+ & water causes both increased hydrostatic pressure and reduced osmotic pressure. This occurs in excessive salt intake with renal insufficiency, such as acute renal failure. Retention of Na+ also causes increased renin-angiotensin-aldosterone secretion.

10 Morphology of Edema:

Diagram showing Capillary System and Mechanisms of Edema Formation

(i) Localized (e.g. Pulmonary edema ; Inflammatory edema ; Cerebral edema).

(ii) Generalized (e.g. Cardiac edema ; Renal edema).

Edema is most commonly seen in subcutaneous tissue.

Subcutaneous Edema may be diffuse or mainly at the dependent part of the body e.g. legs when standing, sacrum when recumbent (influenced by gravity). This is characteristically seen in congestive heart failure.

Renal edema due to nephrotic syndrome is more severe and affects all parts of the body equally. However, initially it may affect loose connective tissue, such as eyelids causing periorbital edema.

Finger pressure displaces interstitial fluid and leaves finger shaped depression, called pitting edema.

Pulmonary Edema is typically seen in - ( Visit: Pulmonary Edema )

Diagram showing pathogenesis of Pulmonary Edema: click here

i) Left ventricular failure, but also seen in

ii) Over transfusion,

iii) Inhalation of poisonous gas,

iv) Nephritic syndrome

v) Adult respiratory distress syndrome, ( Visit: Acute Respiratory Distress Syndrome )

vi) Infections and

vii) Hypersensitive reactions.

Fluid not only accumulates in tissue spaces but also in lung alveoli. As a result gaseous exchange is interfered leading to death.

Gross features: Lungs are two to three times normal weight. Sectioning reveals a frothy blood tinged mixture of air and edema fluid.

Microscopic features : Widening of alveolar septal wall with congestion of the alveolar capillaries. Protein-rich edema fluid in the alveoli are almost cell-free.

Renal edema: 2 types-

1. Nephritic edema in acute nephritis: Edema is not extensive, does not depend on the gravity and protein content is low. Moderate edema is seen as puffiness of face and eyelids. This is due to the retention of Na+ and water due to oliguria resulting from damage of glomeruli. Na+ retention causes increased secretion of renin followed by angiotensin and aldosterone. Congestive cardiac failure is due to associated hypertension, also contribute to edema. (Visit: CONGESTIVE HEART FAILURE )

2. Nephrotic edema in nephrotic syndrome: Hypoproteinemia due to massive proteinuria causes low osmotic pressure of plasma resulting in edema. Associated hyper-aldosteronism releases renin-angiotensin-aldosterone in the system causing edema.

Cerebral edema:

It may be:

1. Localized to the site of injury (Example: abscess, neoplasm) or

2. Generalized ( Example: encephalitis, hypertensive crisis, obstruction to the venous outflow of brain ).

Grossly, brain is swollen with narrowing of sulci and flattening of gyri due to pressure of swollen brain against the skull.

Cardiac edema: (Visit: Cardiac Path Online )

Cardiac edema is due to congestive cardiac failure. Edema is influenced by gravity and is seen in the depending parts of the body (i.e. dorsum of the foot, ankle). Protein content of the edema fluid is low (2%). (Visit: CONGESTIVE HEART FAILURE )

Mechanisms: 3 factors-

1. Reduced left heart output (forward failure) causes diminished renal blood flow producing increased aldosterone secretion with retention of Na+ and water followed by increased blood volume resulting in edema.

2. Right ventricular failure (backward failure) causes increased capillary hydrostatic pressure with increased outflow of fluid from capillary and diminished absorption of tissue fluid producing edema.

3. Retention of tissue metabolites increases tissue osmotic pressure produce edema.

11. Hyperemia and Congestion:

Hyperemia and congestion mean increased volume of blood in a particular site.

Hyperemia is an active process: There is increased blood inflow caused by arteriolar dilation. (Example: skeletal muscle during exercise or at sites of inflammation).

Tissues are redder due to engorgement with oxygenated blood.

Normally, a fraction of the capillaries of an organ or tissue functions, others remain closed. When capillaries are injured (toxic or anoxic) or when more blood is required due to functional over activity, all the capillaries open up resulting in more blood in the part.

In chronic cases the capillary may rupture. This may cause focal hemorrhage and breakdown of erythrocytes at these sites. Hemosiderin-laden macrophages are often present.

Parenchymal cell atrophy or death may cause scarring.

Gross features: The involved organs appear brown with contraction and fibrosis - Example: Lungs ; Liver.

Congestion is a passive process: It is caused by impaired outflow from a tissue.

Isolated venous obstruction may cause local congestion.

Systemic venous obstruction occurs in congestive heart failure.

Tissues acquire a blue-red color (cyanosis) due to accumulation of deoxygenated hemoglobin.

Long-standing stasis may result in cell death. (Visit: CONGESTIVE HEART FAILURE )

Causes: (Visit: Cardiac Path Online ; Pulmonary Pathology Online )

a) Heart: Mitral valve disease (Example: stenosis/incompetence). Congenital heart disease (e.g. pulmonary stenosis, tricuspid regurgitation) and Myocardial infarct ; Cardiomyopathy.

(Visit: congenital heart disease ; CARDIOMYOPATHY ; Myocardial infarction )

b) Lung: Emphysema ; Pulmonary fibrosis. It causes reduction of pulmonary circulatory bed producing right heart failure leading to passive venous congestion.

Morphology:

Heart: In mitral stenosis heart shows hypertrophy and dilation of left atrium with formation of ball thrombus.

Lungs:

Gross features:

Grossly, lung is voluminous with impression of ribs, pits on pressure, dark brown in color, and feels firm.

Microscopic features:

Microscopically, alveoli contain edema fluid with intra alveolar hemorrhage (cause of hemoptysis) and "Heart failure cells" (hemosiderin filled macrophages).

Histopathology Image of Heart Failure Cells: click here

(Hemolysis of alveolar RBC liberates hemosiderin and bilirubin. Alveolar phagocytes engulf hemosiderin and carry them throughout the framework of lung, which stimulates fibrosis producing brown induration of lung and bilirubin cause latent jaundice).

Liver:

Gross features:

Liver is enlarged and soft. Cut surface shows alternate dark and pale areas ("Nutmeg liver") - dark area represent congested centrilobular zone and pale areas represent fatty middle zone and normal periportal areas. Macroscopic image of Nutmeg Liver: click here

Microscopic features: Histopathology Image of Liver showing Nutmeg Pattern due to Congestion around the Central Veins: click here

1. In centrilobular zone central vein and sinusoids are distended with blood and liver cells show necrosis (due to anoxia and pressure).

2. Mid zone shows fatty change.

3. Periportal zone is relatively normal (better oxygenated due to their proximity to hepatic arterioles.

In long-standing cases central vein is thickened with extension of fibrous tissue in to the surrounding lobules

Persistent hypoxia prevents regeneration of liver cells hence called cardiac sclerosis instead of cardiac cirrhosis.

12 Hemostasis and Thrombosis:

Hemostasis is a normal physiologic process. It maintains blood in fluid condition and clot-free state in normal vessels by inducing a rapid and localized hemostatic plug at sites of vascular injury.

Thrombosis represents a pathologic state in which there is formation of intra-vascular solid mass (thrombus) from the elements of circulating blood. The vessel may be uninjured or with minor injury.

Thrombosis:

Three primary factors influence thrombus formation (Virchow’s triad):

1. Endothelial injury.

2. Slowing of blood flow.

3. Hyper coagulability of blood.

1. Endothelial injury commonest cause, mainly in the heart and arterial circulation (e.g. Myocardial infarction, endocarditis, ulcerated atherosclerosis). Injury may occur from diverse causes e.g. hemodynamic stress (hypertension or turbulent flow in aneurysms), radiation, products absorbed from cigarette smoke, extensive burn etc.

2. Slowing of circulation (alteration in normal blood flow):

Normal blood flow is laminar (i.e., the cellular elements flow centrally inside the vessel, separated from endothelium by a clear zone of plasma).

Stasis and turbulence disrupt laminar flow and bring platelets into contact with the endothelium.

They prevent dilution of activated clotting factors by fresh flowing blood, retard the inflow of clotting factor inhibitors and permit the build-up of thrombi.

Stasis is important in causing thrombosis in veins, cardiac chambers and arterial aneurysms.

Hyperviscosity syndrome - Example: In polycythemia or deformed RBC as in sickle cell anemia causes stasis in small blood vessels predisposing to thrombosis.

3. Hypercoagulability of blood may be due to heritable gene mutation or acquired.

Example: Severe burn, shock, oral contraceptive, increased hepatic synthesis of coagulation factors and reduced synthesis of anti-thrombin III.

Mechanism:

Normally, in a blood vessel, cellular elements flow centrally, forming axial stream separated from endothelium by a clear, cell-free, plasmatic zone. Due to slowing of the circulation, platelets come in contact with endothelium and are activated to liberate tissue factors. Tissue factors recruit more platelets, which are deposited in the form of ridges at right angles to the blood flow forming corrugations, known as line of Zahn. Coming in contact with sub-endothelial collagen, platelets are activated to release ADP, Thromboxanes etc. ADP aggregate more platelets.

Thromboplastin, liberated from platelets and injured endothelium initiate precipitation of fibrin on the surface of platelets. Fibrin network may entangle RBC and leucocytes.

A thrombus is thus formed, on the basis of platelets and fibrin, with varying number of RBC and leucocytes.

Thrombi may form anywhere in the cardiovascular system.

Aortic and cardiac thrombi are typically nonocclusive (mural) as a result of rapid and high-volume flow.

Smaller arterial thrombi may be occlusive.

All these thrombi usually begin at sites of endothelial injury (e.g. atherosclerotic plaque) or turbulence (vessel bifurcation).

Venous thrombi characteristically occur in sites of stasis and are occlusive.

At sites of origin, thrombi are generally firmly attached. Arterial thrombi tend to extend retrograde from the attached point, where as venous thrombi extend on the direction of blood flow. The propagating tail may not be well attached and may fragment to create an embolus.

Sites of thrombus formation:

Cardiac and arterial thrombi are formed slowly in rapid circulation. They are pale-gray and tend to have gross and microscopic lamination (lines of Zahn) produced by pale layers of plates and fibrin alternating with darker red cell-rich layers. These are mostly seen in the left ventricle overlying an infarct, ruptured atherosclerotic plaques, and aneurysmal sacs.

Venous thrombosis (phlebothrombosis) often created a long red-blue cast of the vein lumen as it occurs in a relatively slow circulation. The thrombus contains more enmeshed erythrocytes among sparse fibrin strands (red or stasis thrombus).

Fibrin and attachment to the vessel wall distinguish stasis thrombus from postmortem clot. Phlebothrombosis is most commonly (more than 90 %) seen in the veins of the lower extremities.

Thrombi may also form on heart valves. In infective endocarditis, bacteria or fungi form large infected thrombi (vegetations), causing underlying valve damage and systemic infection. Sterile vegetations (nonbacterial thrombotic endocarditis) can also develop on noninfected valves in patients with hypercoagulable states, particularly in those with disseminated cancer. Noninfective, verrucous(Libman-Sacks) endocarditis is seen in patients of SLE due to circulating immune complex.

Heart:

i) Ball thrombus is seen in left atrium in mitral stenosis. It is large and spherical.

ii) Mural thrombus is seen over the wall of heart in cardiac infarct, cardiomyopathy

iii) Agonal thrombus is seen in right ventricle in case of death due to pneumonia.

iv) Vegetations over the cardiac valves are seen in endocarditis.

Artery:

i) On the atheromatous patch in coronary, cerebral, spleen, and renal arteries.

ii) Laminated thrombus is seen in aneurysmal sac.

iii) Marasmic thrombus is seen in marasmic children, in mesenteric artery (stasis)

Vein:

Veins are the commonest sites of thrombus formation due to slow circulation.

Other causes of venous thrombosis are:

i) Trauma, burn, due to reduced physical activity, injury to vessels and release of pro-coagulants from tissue.

ii) Puerperal and postpartum thrombosis occurs mainly due to amniotic fluid infusion into blood and hypercoagulability in late pregnancy and in postpartum period. .

iii) Disseminated cancer, due to release of tumour-associated -procoagulants.

iv) Advanced age, bed rest, immobilization, reduced physical activity diminishes milking action of muscle.

v) Thrombophlebitis is the inflammation of the venous wall due to septic thrombus.

Example: a) Pelvic veins in puerperal sepsis ; b) Portal vein in acute appendicitis ; c) Cavernous sinus in facial infection

Fate of a thrombus:

Septic thrombus causes abscess formation.

Aseptic thrombus may show:

i) Propagation causing complete vessel obstruction.

ii) Dissolution by fibrinolytic action.

iii) Detachment- with embolism.

iv) Organization and recanalization, re-establishing vascular flow by in-growth of endothelial cells, smooth muscle cells and fibroblasts to create through-and through capillary channels or by incorporating the thrombus as a sub-endothelial swelling of the vessel wall.

Effect of thrombosis:

Septic: Forms abscess and may cause pyaemia.

Aseptic: Effect will depend upon the vessel involved and efficiency of the collateral circulation of the area.

1. Arterial thrombus - in a small vessel is occlusive and usually causes infarction. This is particularly seen when it involves organs supplied with end-arteries (Example: cerebral, coronary, splenic, mesenteric and renal arteries).

2. Venous thrombosis - rarely causes infarction, as collateral channels soon enlarge to maintain the venous drainage.

Superficial venous thrombosis, as in varicose saphenous veins, causes local edema and impaired venous drainage, predisposing to skin infection and varicose ulcer.

Deep thrombi in larger leg veins above the knee (Example: popliteal, femoral and iliac veins), have good collateral circulation but commonly embolize (about 50 % cases).

Occlusive venous thrombi with poor collateral channels cause increased venous and capillary pressure forming edema (Example: ascites in portal vein thrombosis).

Beneficial effect of thrombosis:

Thrombosis causes hemostasis and sealing of the vessel wall after erosion by malignant tumours and attempts to prevent hematogenous spread.

Blood clot: Coagulation of dead blood (Example: in a test tube, in a blood vessel after death or after ligature).

Types of clot:

1. Current jelly clot (soft and red) forms rapidly in great vessels or heart. All the elements of blood are involved.

2. Chicken fat clot (lower part dark, upper part yellow) forms slowly, RBC settles at the bottom and pale upper part consists of leucocytes and fibrin.

13 Embolism:

1)Diagram showing Sources of Arterial Emboli: click here

2)Diagram showing Sources of Venous Emboli: click here

Embolism is the intra-vascular impaction of an undissolved material (solid, liquid or gaseous) carried by the blood stream to a site distant from its point of origin.

Material impacted is called embolus.

Most (99%) emboli arise from thrombi, hence the term thromboembolism.

Other forms include droplets of fat, gas bubbles, atherosclerotic debris ( atheroemboli ), tumour fragments, bone marrow, or foreign bodies such as bullets.

Emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion and ischemic necrosis of the distal tissue ( infarction ).

Pulmonary Thromboembolism:

In more than 95 %, pulmonary emboli originate from deep leg vein thrombi. Depending on the size, a pulmonary embolus may occlude the main pulmonary artery, impact across the bifurcation (saddle embolus), pass into smaller arterioles.

Multiple emboli may occur, either sequentially or as a shower of small emboli from a single large mass. In general, one pulmonary embolism puts a patient at risk for more.

Rarely, emboli pass through atrial or ventricular defects into the systemic circulation (paradoxical embolism) - Example: cerebral embolism with hemiplegia due to puerperal thrombosis of pelvic veins.

Fat Embolism:

Air Embolism:

Decompression Sickness:

Amniotic Fluid Embolism:

Source of Emboli:

Left Cardiac thrombi (80 %) are mural thrombi in myocardial infarct and thrombi in left atrium in rheumatic mitral valve disease.

Systemic artery thrombi, from aortic aneurysm, and ulcerated atherosclerotic plaques in aorta and other arteries are impacted in organs like liver, brain, viscera and in extremities.

Venous and right cardiovascular thrombi produce pulmonary embolism e.g. detached venous thrombi, tumour cells invading veins, fat embolism, air embolism amniotic fluid embolism.

Portal and mesenteric vein thrombi due to inflammation in gastrointestinal tract are impacted in liver.

Effects of Embolism: Depends on the type and site of embolism.

i) Septic emboli produce abscess.

ii) Tumor emboli cause metastatic tumor

iii) Organ with end-arteries/poor collateral circulation produces infarct.

iv) Condition of heart and collateral circulation e.g., femoral artery with sound heart causes temporary paresis with re-establishment of circulation by collaterals.

Femoral artery embolism with feeble heart in old age causes dry gangrene

Retrograde Embolism:

Normally emboli move in the direction of the flow.

If it moves to opposite direction and gets impacted, it is called retrograde embolism.

Examples:

i) Virchow’s gland-(deep supra-clavicular lymph node) in gastric carcinoma.

ii) Inguinal lymph nodes in testicular tumour.

iii) Krukenburg’s tumor in mucoid carcinoma of gastrointestinal tract.

14. Infarct

Infarction: Infarct is an area of ischemic necrosis due to occlusion of arterial supply in most cases.

Diagram showing common sites of Systemic Infarction from Arterial Emboli: click here

The word "infarction" comes from the Latin "infarcire" meaning "to plug up or cram."

- Total occlusion of an artery produces an area of coagulative necrosis called an infarct.

- Partial occlusion - that is, stenosis - occasionally causes necrosis, but more commonly leads to a variety of degenerative cell changes. These changes include vacuolization of cells, atrophy, loss of muscle cell myofibrils, and interstitial fibrosis. Infarction of vital organs such as the heart, brain, and intestine may be life-threatening.

If the individual survives, the infarct heals with a scar, which is the common occurrence in less vital organs.

Most cases of infarction are due to thrombosis or embolism. Rarely, there are other causes - Examples: vasospasm, extrinsic compression of a vessel by tumour, edema, or entrapment in a hernia sac, and twisting of vessels, such as testicular torsion or bowel volvulus. Traumatic vessel rupture is a very rare cause.

Occluded venous drainage (e.g. venous thrombosis) can cause infarction but more often induce congestion only (due to rapid blood flow through collaterals).Infarcts due to venous thrombosis are more likely in organs with single venous outflow, such as testis or ovary.

Pulmonary Infarction ; Myocardial Infarction

Factors that influence development of an infarct:

1. Pattern of vascular supply:

Organs with dual circulation (lung, liver) or anastomosing circulation (radial and ulnar arteries, circle of Willis, small intestine) protect against infarction.

Organs supplied with end arteries (spleen, kidneys) usually develop infarct after occlusion of the arterial supply.

2. Rate of development of occlusion:

Slowly developing occlusions less often cause infarction by providing time to develop alternate perfusion pathways.

(Example: collateral coronary circulation).

3. Changes due to hypoxia:

Neurons undergo irreversible damage after 3 to 4 minutes of ischemia, myocardial cells die only after 20 to 30 minutes.

In contrast, fibroblasts within ischemic myocardium are viable even after many hours.

4. Oxygen content of blood:

Anemia, cyanosis, or congestive heart failure (with hypoxia) may cause infarction.

Infarct morphology:

Morphologically, the necrotic tissue of an infarct swells, and the infracted area often protrudes above the surface of the organ.

As an infarct ages it undergoes fibrosis, reduces in size, and ultimately shrinks below the surface of the organ.

A fresh infarct is pale because of the loss of red blood cells, an appearance reflected in the terms white or pale infarct.

Infarcts can also be red (hemorrhagic), particularly in the lung and the intestine.

With time, the tissue surrounding an infarct forms granulation tissue rich in sprouting capillaries that bleed easily. Therefore, the border of a healing infarct frequently is hemorrhagic.

Infarcts may also be either septic or bland

Red infarcts occur:

- In venous occlusion ( Example: ovarian torsion)

- In loose tissues (such as lungs, placenta)

- In tissues with dual circulation (Example: lungs and small intestine)

- In tissues previously congested because of sluggish venous outflow.

- At a site of previous occlusion and necrosis when flow is re-established.

White infarcts occur in solid organs - Examples: heart, spleen and kidney, with end arterial circulation.

Pathogenesis and pathology:

Arterial obstruction causes fall of distal blood pressure to capillary pressure with dilation of capillaries causing injury due to anoxia. This is the commonest cause.

Blood from the veins accumulates in the dilated and injured capillaries with outpouring of fluid and RBC into the surrounding tissue.

Thus, the area becomes red, engorged and even hemorrhagic with venous blood, hence the term infarction.

Gross features:

-All infarcts tend to be wedge-shaped, the occluded vessel marks the apex, and the organ periphery forms the base.

-Lateral margins may be irregular reflecting the pattern of adjacent vascular supply.

Microscopic features:

- Features of ischemic coagulative necrosis.

- An initial inflammatory response. This may last for hours to days.

- This is followed by a reparative response. This may last from days to weeks.

- The changes usually begin in the preserved margin.

- In stable or labile tissues, some parenchymal regeneration may occur where the underlying stromal architecture is spared.

- Most infarcts are ultimately replaced by scar tissue. The brain is an exception. In the brain there is liquifaction followed by absorption and cyst formation.

- Septic infarctions occur with embolization of infected cardiac vegetations or when microbes seed an area of necrosis.

- The infarct becomes an abscess.

- Abscess slowly organize to scar.

15. Hemorrhage

Hemorrhage (i.e. bleeding) is a discharge of blood from the vascular compartment to the exterior of the body or into nonvascular body spaces.

The most common and obvious cause is trauma - usually accidental, but often by the surgeon's scalpel.

A blood vessel may be ruptured in ways other than laceration.

For instance, severe atherosclerosis may so weaken the wall of the abdominal aorta that it balloons to form an aneurysm, which then bleeds into the retroperitoneal space. The aneurysm may complicate a congenitally weak cerebral artery (berry aneurysm) and lead to cerebral (subarachnoid) hemorrhage.

Certain infections - for example, pulmonary tuberculosis erode blood vessels ; a similar vascular injury is caused by invasive tumours.

Hemorrhage also results from damage at the level of the capillaries - for instance, the rupture of capillaries by blunt trauma.

Increased venous pressure also causes extravasation of blood from capillaries in the lung. Pulmonary Hemorrhage (Eg. Goodpasture's Syndrome)

Vitamin C deficiency is associated with capillary fragility and bleeding, owing to a defect in the supporting structures.

It is important to recognize that the capillary barrier by itself is not sufficient to contain the blood within the intravascular space.

The minor trauma imposed on small vessels and capillaries by normal movement requires an intact coagulation system to prevent hemorrhage.

Thus, a severe decrease in the number of platelets (thrombocytopenia) or a deficiency of a coagulation factor (Eg: Factor VIII in hemophilia) is associated with spontaneous hemorrhages unrelated to any apparent trauma.

An individual may exsanguinate into an internal cavity, as in the case of gastrointestinal hemorrhage from a peptic ulcer (arterial hemorrhage) or esophageal varices (venous hemorrhage).

In such case large amounts of fresh blood fill the entire gastrointestinal tract.

When a large amount of blood accumulates in soft tissue, it is known as hematoma.

Such a collection of blood can be merely painful, as in a muscle bruise, or fatal, if located in the brain.

Diffuse superficial hemorrhages in the skin are termed purpura or ecchymoses.

Following a bruise or in association with a coagulation defect, an initially purple discoloration of the skin turns green and then yellow before resolving, a sequence that reflects the progressive oxidation of bilirubin released from the hemoglobin of degraded red blood cells.

A good example of an ecchymosis is a "black eye".

A minute punctuate hemorrhage, usually in the skin or conjunctiva, is labelled a petechia.

This lesion represents the rupture of a capillary or arteriole and is seen in conjunction with coagulopathies or vasculitis ,the latter is classically associated with bacterial endocarditis. ( Visit: INFECTIVE ENDOCARDITIS )