8/13/2019 Infection Diseases http://slidepdf.com/reader/full/infection-diseases 1/28 VIRAL INFECTIONS POLIOMYELITIS Poliomyelitis (Greek: polios – “grey”. myelos – “spinal cord”) Is a acute viral infection of the motor nerve endings, commonly of grey matter of anterior horns of spinal cord. his is a childhood infection. Cause: uncoated single!stranded "#$ %icornaviridae viruses Pathogenesis: &roplet and smear infection occurs through direct contact 'ith affected persons. Incuation !e"io# : usually of ! days, *ut may last for month. he permanent immunity is conferred after %oliomyelitis. $ virus initially replicates in the tissue at the point of entry, i.e. pharyn+ and ileum and in the local lymphoid tissues. ommonly vtrus is confined in lymphoid follicles and giving rise to the ina!!a"ant form of poliomyelitis. -atent immunity is undou*tedly conferred *y this pharyngitis 'ithout a spread of the infection to the central nervous system. ther'ise virus can penetrate the local lymph nodes (mesenterial and neck lymph nodes), 'hich is follo'ed *y primary viremia and a central focus of virus proliferation. &isseminated in different organs, virus progresses to secondary viremia, causing $isce"al or ao"ti$e form of manifestation of disease. his is characterised *y degenerative, necro*iotic and inflammatory changes in *rain, skin and meningeal layers. nly in / of cases virus can involve the central nerve system, passing through hemato!encephalic *arrier. he virus spreads *y the a+is!cylinders of the pyramidal tracts to the #0. 1very part of the central nervous system may *e affected2 lesions are seen mainly in the asal ganglia% mi#"ain% me#ulla% co"# and !e"i!he"al ne"$es& here, they cause necrosis of the ganglion cells and a reactive perivascular inflammatory infiltrate that initially contains granulocytes and later lymphocytes and plasma cells. -ater reactive proliferation of glial cells occur. he glial cells phagocyti3e the remains of the ganglion cells – neu"ono!hagy develops. his is later follo'ed *y "e!a"ati$e gliosis of the anterior horn. hus paralysis and neurotrophic atrophy of skeletal muscles are developed. here are the follo'ing forms of poliomyelitis: • Ina!!a"ant 'o"m( • Visce"al o" ao"ti$e 'o"m( • Meningeal 'o"m( • Pa"alytic 'o"m& Inapparant, visceral and meningeal forms are termed non)!a"alytic 'o"ms and appear in 44/ of all cases of poliomyelitis. Ina!!a"ant 'o"m is characterised *y involvement of pharyngeal and intestinal lymphoid tissues. Visce"al 'o"m disease can *e manifested *y catarrhal inflammation of respiratory and gastro! intestinal tract. Meningeal 'o"m appears as serous meningitis. he most serious form of poliomyelitis, 'hich characterised *y spinal paralysis is Pa"alytic 'o"m . here are 5 stages of %aralytic form: 1. Preparalytic; 2. Paralytic; 3. Recovery; 4. Residual. 1
Poliomyelitis (Greek: polios – “grey”. myelos – “spinal cord”) Is a acute viral infection of the motornerve endings, commonly of grey matter of anterior horns of spinal cord. his is a childhoodinfection.Cause: uncoated single!stranded "#$ %icornaviridae virusesPathogenesis: &roplet and smear infection occurs through direct contact 'ith affected persons.Incu ation !e"io# : usually of ! days, *ut may last for month. he permanent immunity isconferred after %oliomyelitis.$ virus initially replicates in the tissue at the point of entry, i.e. pharyn+ and ileum and in the locallymphoid tissues. ommonly vtrus is confined in lymphoid follicles and giving rise to theina!!a"ant form of poliomyelitis. -atent immunity is undou*tedly conferred *y this pharyngitis'ithout a spread of the infection
to the central nervous system.ther'ise virus can penetrate the local lymph nodes (mesenterial and neck lymph nodes), 'hich isfollo'ed *y primary viremia and a central focus of virus proliferation. &isseminated in differentorgans, virus progresses to secondary viremia, causing $isce"al or a o"ti$e form of manifestation ofdisease. his is characterised *y degenerative, necro*iotic and inflammatory changes in *rain, skinand meningeal layers.
nly in / of cases virus can involve the central nerve system, passing through hemato!encephalic *arrier. he virus spreads *y the a+is!cylinders of the pyramidal tracts to the #0. 1very part of the central nervous system may *e affected2 lesions are seen mainly in the asalganglia% mi# "ain% me#ulla% co"# and !e"i!he"al ne"$es& here, they cause necrosis of the
ganglion cells and a reactive perivascular inflammatory infiltrate that initially contains granulocytesand later lymphocytesand plasma cells. -ater reactive proliferation of glial cells occur. he glial cells phagocyti3e theremains of the ganglion cells – neu"ono!hagy develops. his is later follo'ed *y "e!a"ati$e gliosis of the anterior horn. hus paralysis and neurotrophic atrophy of skeletal muscles are developed. here are the follo'ing forms of poliomyelitis:
Inapparant, visceral and meningeal forms are termed non)!a"alytic 'o"ms and appear in 44/ of allcases of poliomyelitis.Ina!!a"ant 'o"m is characterised *y involvement of pharyngeal and intestinal lymphoid tissues.Visce"al 'o"m disease can *e manifested *y catarrhal inflammation of respiratory and gastro!intestinal tract.Meningeal 'o"m appears as serous meningitis.he most serious form of poliomyelitis, 'hich characterised *y spinal paralysis is Pa"alytic 'o"m .here are 5 stages of %aralytic form:
1. Preparalytic stage is associated 'ith a sore throat, cough, a raised temperature, increased pulse!rate and meningeal symptoms. his period lasts 6!7 days. 8icroscopic e+amination of neuronsreveals: loss of tigroid matter and thus paleness of nerve cells, necrosis of fe' neurons.2. Paralytic stage. he lesions are seen in the motor neurons of *asal ganglia, mid*rain, medulla andanterior horns of cord. 8any nerve cells sho' chromatolysis due to the direct action of the virus.%erivascular infiltration, and all stages of nerve degeneration and a*sor*tion *y the glial
neuronophagic cells ! reparative gliosis are 'ell seen. he infiltration is mainly lymphocytic though acertain num*er of polynuclear cells are to *e found round the vessels. 0mall hemorrhages 'ithedema are visi*le in the grey matter.
his period lasts from several days to !6 'eeks. $ccording to localisation of pathomorphologicalchanges in #0, paralytic form is also su*divided into 5 clinical form: spinal, bulbar, pontial andmixed .
Spinal orm is the commonest, and characterised *y the damage, limited to the anterior horns ofspinel cord. %atients e+hi*it paralysis, usually in the e+tremities. "espiratory paralysis can *e fatal,due to respiratory insufficiency, atelectasis, circulatory distur*ances, 'hich is clinically seen asattacks of dyspnea and choking. here is neurotrophic atrophy of attended skeletal muscles.
!ulbar orm. -esion occurs in medulla o*longata, 'here situated the important nerve centers. hisis fatal condition. &ysphagia can *e associated 'ith choking 'hen s'allo'ing is attempted. heattacks of dyspnea, 'ith respiratory insufficiency also occur. Pontial orm. &ue to localisation of nuclei of 9II cranial nerve in pons, poliomyelitic lesion ischaracterised *y facial paralysis, and atrophy of dependent mimetic muscles.
"ixed orm occurs rarely and is manifested *y ponto!*ul*ar!spinal symptoms.3. Recovery stage may last from months to ,7 year. $t the site of neuronophagial nodules thegliosis takes place. he necrotic areas of *rain matter are replaced *y cysts. &estroyed functionscan *e partly recovered.4. Residual stage is characterised *y the complications as: paralysis, atrophy of skeletal muscles,deformation and osteoporosis of *ones, contracture of ;oints ! disa*ility appears.
INFL*EN+A
Influen3a is a contagious viral infection of the respiratory tract that causes coughing, *reathingdifficulty, fever, headache, muscle aches and 'eakness.
Pathogen: In'luen,a Vi"us is RNA $i"us of A% -, and C types, related to O"thomy.o$i"i#ae . ype$ is usually responsi*le for the large out*reaks and is a constantly changing virus. #e' strains ofype $ virus develop regularly and cause ne' epidemics every fe' years. ype < causes smallerout*reaks, and ype usually causes mild illness.
E!i#emiology& Influen3a is transmitted from person to person via contagious droplets that are spread'hen an infected person snee3es or coughs. $ transplacental transmission from mother to em*ryoalso occurs. Pathogenesis: &roplet infection leads to adhesion of the virus to the ciliated epithelium *y means oft'o surface proteins it uses as “spikes.” hese include neuraminidase, 'hich e+poses sugar, andhemagglutinin (viral lectin), 'hich leads to adhesion of the virus to the e+posed sugars (glycophorin$). he virus then migrates into the cytoplasm 'hen the viral fusion peptide is released *y lysosomal
proteolysis. his results in the formation of giant cells from infected host cells. <ecause of the genetic insta*ility of the virus, its antigenicity vary from one epidemic to the ne+t.herefore there is effectively no immunity against it.
$ virus initially replicates in the *ronchial and alveolar epithelium. his is follo'ed *y primaryviremia. &ue to organotropism, virus is disseminated in nasal, laryngeal, tracheal and *ronchialmucosal epithelium, leading to catarrhal inflammation of them.
Incu ation !e"io# lasts from a fe' hours to ! days.
Mo"!hology: &ue to cytopathic and vaso!paralytic peculiarities of influen3a virus, a hemorrhagicnecroti3ing inflammation develops. here are hyperemia, edema, inflammatory infiltrations anddiapedesis hemorrhages in mucosa and su*mucosa. he epithelium undergo to necrosis anddes=uamation. &ue to de!epithelisation and immune!depressive action of viruses secondary *acterialinfection is superadded.
$ccording to severity there are 6 forms of influen3a: mild, medial and severe forms.Mil# or am ulato"y in'luen,a is the fre=uent form. he process involves upper respiratory tract,'ith development of catarrhal rhinitis, pharyngitis, tracheitis and *ronchitis. o+emia is also mild.8ucosal and glandular epithelium undergo to hydropic degeneration and des=uamation. 0ymptomsare fever, chills, headache, nasal discharge, cough, sore throat and loss of appetite.
his form lasts for one 'eek only, 'ith complete resolution.he most common method for diagnosis of influen3a is the detection of cytoplasmic inclusions *y
tests, 'hich are done on nose and throat (nasopharyngeal) secretions *y s'a**ing.here are t'o cytoplasmic inclusions, characteristic for influen3a :
• oxyphilic substances ! the destruction materials of epithelium2• basophilic substances ! the cytoplasmic microcolonia of viruses.
Me#ial 'o"m of influen3a lasts for one month and usually results in complete resolution.Inflammatory process e+tends do'n'ard to the lo' respiratory 'ays. In the upper respiratory 'ays,hemorrhagic and necrotic tracheo*ronchitis develops. *struction of *ronchi and *ronchioles *ye+udative masses forms focuses of emphysema. &ue to the destruction of second type of
alveolocytes, 'hich produce a surfactant, leads to focal lung collapse or atelectasis. In alveoles thereis serous e+udate 'ith red cell mi+ture, alveolar septa are thickened *y inflammatory infiltration ! adiffuse interstitial pneumonia develops.In children also may appear hyaline mem*ranes. $ll these changes are referred to as in'luen,a!neumonia& he further immune suppression leading to postviral superinfection may lead to developing ofsevere influen3a.Se$e"e 'o"m of influen3a 'ith sudden onset, is associated 'ith a prolonged high fever and severemalaise. It may develop in t'o variant:• Se$e"e gene"al to.emia 2• Pulmona"y com!lications , due to superimposed secondary infections.
Se$e"e gene"al to.emia occurs *ecause of cytopathic and vasopathic action of influen3a virus. Inthis condition the follo'ing changes occur in respiratory tract: the necrotic changes of mucosaepithelium and serous!hemorrhagic pneumonia.
&ue to virusemia and vasoparalytic action of influen3a virus, congestion, edema, diapedesis,hemorrhages in serous, mucous coverings, skin and internal organs appear. #emorrhagicencephalitis is one of the manifestation of severe influen3a infection. &amages the microvasculature,lead to disseminated hemorrhages. <leeding may occur in the form of diapedesis, focal *leeding ormassive hemorrhages, 'hich *y itself may *e fatal. he diapedesis leads to disseminated tissuenecrosis and eventually to fatal cere*ral edema.
Pulmona"y com!lications of severe influen3a develop due to superimposed secondary infections.his form of severe disease appears *ecause of immune!suppressive action of influen3a virus.
%ostviral superinfection 'ith staphylococci, streptococci, pneumococci or *lue pus *acillus canchange the clinic of disease: necrotic pan*ronchitis 'ith sloughing of epithelium and purulent
*ronchopneumonia take place. -ungs *ecome enlarged and get motley appearance ) / La"ge motleyin'luen,a lung/ . %leura may also *e involved, 'ith the resultant empyema development.
he *oth severe forms of influen3a are accompanied 'ith severe dyscirculatory changes of all
organs2 in heart, lungs and liver occur edema, hemorrhage, degenerations, interstitial inflammations,destruction of intramural nerves and throm*ophle*itis. In *rain ! serous!hemorrhagic meningitis,encephalitis and edema develops.
Com!lications of influen3a are usually developed in lung, heart and - " organs. he most seriousvariants are: chronic pneumonia, chronic *ronchitis, *ronchiectasis, emphysema, carnification,
pneumosclerosis2 in children along 'ith a*ove complications, meningitis and croup 'ith asphy+ia arecommon as 'ell. ertain individuals are at higher risk from complications of influen3a: %eople aged 7> or older,
people 'ith conditions such as heart disease, lung disease such as asthma, kidney pathologies,transplant recipients, people 'ith ?I9, and especially children, 'hich immune system is lessadapted.
%aramy+oviridae%arainfluen3a 9irus%athogen that causes flu and croup syndrome.linical presentation and morphology: hese viruses (types I!I9 a and *) are genetically sta*le.hey multiply in the respiratory ciliated epithelia, damaging it and causing flu!like disorders andcroup syndrome, primarily in children (
MEASLES
8easles or 8or*illi (-atin: morbus – illness2 greek: rubeola ) is an acute highly contagious viraldisease, 'hich usually involves children aged from months to 7 years old. It is characteri3ed *yfever, @" (upper respiratory tract) catarrhal inflamation, AoplikBs spots and maculopapules.
Pathogen : Measles Vi"us ! a paramy+ovirus. it is spherical in appearance. It has an outer envelopecomposed of 8!protein, ?!protein, C!protein, and internal core is "#$.Incu ation !e"io#: >!day.E!i#emiology: It is a strict anthroponosis and the patients only are the source of infection &0pread
*y droplet infection. he permanent immunity ac=uire after disease.Pathogenesis: he ? antigen of viral envelope, causes hemagglutination. he virus uses also its Cantigen to penetrate the ciliated respiratory epithelium, inducing infected cells to fuse 'ith uninfectedcells to form giant cells. he virus replicates 'ithin these giant cells, causing primary viremia andinfecting primarily the cells in lymphatic organs. his then leads to secondary viremia and generalto+ic symptoms.8easles can *e detected from *lood and nasal, pharyngeal secretions. Mo"!hology: Clinical !"esentation& 8easels develops in 5 stages: Incu ation stage% !"o#"omal stage% e"u!tionstage% con$alescent stage &•
Incu ation stage lasts appro+imately > days.• P"o#"omal stage is characteri3ed *y fever, catarrhal inflammation of @" – rhinitis, laryngitis,tracheitis, *ronchitis, con;unctivitis, general to+ication, cough2 and enanthema – AoplikBs spots.
E!i#emiology: ?I9 is a se+ually transmitted disease. Infection is aided *y -angerhans cells inmucosal epithelial surfaces 'hich can *ecome infected. ?I9 can also *e spread via *lood or
*lood products, most commonly 'ith shared contaminated needles used *y persons engaging inintravenous drug use. 8others 'ho are ?I9 infected can pass the virus on to their fetuses inutero or to infants via *reast milk.
ther transmission methods are rare and include accidental needle in;ury, artificial insemination 'ithdonated semen, and through a donated organ.
Pathogenesis: he &5 !lymphocytes have surface receptors to 'hich ?I9 can attach to promoteentry into the cell. he infection e+tends to lymphoid tissues 'hich contain follicular dendriticcells that can *ecome infected and provide a reservoir for continuing infection of &5 !lymphocytes.
Ehen ?I9 infects a cell, it must use its reverse transcriptase en3yme to transcri*e its "#$ to hostcell proviral &#$. It is this proviral &#$ that directs the cell to produce additional ?I9virions 'hich are released. he genome of ?I9 contains genes, 'hich direct the formation of the *asic components of?I9. hese genes directs production of the outer envelope glycoprotein, 'hich is responsi*lefor tropism to &5 receptors, and transmem*rane glycoprotein, 'hich cataly3es fusion of?I9 to the target cellHs mem*rane. In addition to the &5 receptor, a coreceptor kno'n as achemokine is needed for ?I9 infection. here are strains of ?I9 kno'n as !tropic strains'hich selectively infect lymphocytes. he 8!tropic strains of ?I9 infect macrophages. &ualtropic ?I9 stains have *een identified. he presence of a mutation may e+plain the
phenomenon of resistance to ?I9 infection in some cases. ver time, mutations in ?I9 mayincrease the a*ility of the virus to infect cells via these routes.
Clinical !"esentation& $I&0 develops in 5 period:
• Latent !e"io#(• ;ene"ali,e# lym!ha#eno!athy(
• P"e)AI5S(
• AI5S&
Latent !e"io#& &isease *egins 'ith ?I9 infection. %eople infected 'ith ?I9 may have nosymptoms for ten years or longer, *ut they can still transmit the infection to others during thissymptom!free period. <lood analysis reveals ?I9 and anti!?I9 anti*odies.
;ene"ali,e# lym!ha#eno!athy& his stage lasts appro+imately 6!7 years. &ifferent groups of lymphnodes *ecome s'ollen ! a chronic lymphadenopathy syndrome is developed. 8icroscopice+amination of lymph nodes reveals non!specific follicular hyperplasia of <!3ones.
P"e)AI5S . 8ean'hile, the immune system gradually 'eakens and asymptomatic form develops toearly symptomatic ?I9 infection, 'ith such common symptoms as fever, s'eat (particularly atnight), lymphadenopathy, chills, 'eakness, 'eight loss, flu!like symptoms and diarrhea.
AI5S& his is a very advanced ?I9 infection Ehen the &5 lymphocyte count drops *elo'>> microliter, then the stage of clinical $I&0 has *een reached. In peripheral *lood the anti!?I9anti*odies almost have not *een revealed, *ut ?I9 are in a large amount. his is the point at 'hich,
due to of complete failure of immune system, the characteristic opportunistic infections andneoplasms of $I&0 appear.
<ecause of impairment of lymphoid tissue, lymph nodes are reduced, even hardly detected.
In central nerve system P"og"essi$e multi'ocal leu1oence!halo!athy develops. he process usually
involve the su*cortical nuclei and 'hite matter of *rain. he little glial nodules, vacuoli3ation andsoftening focuses appear at this sites. hese changes result in a =uick decline in cognitive and motorfunctions. $I&0 &ementia ! 'orsening and slo'ing of mental function occurs as 'ell.
he symptoms of $I&0 are primarily the result of Fopportunistic infections.F hese diseases in theimmunocompromised host appear as an over'helming infection, that no respond to treatment
he most fre=uent infection is %neumocystis carinii pneumonia, F% % pneumoniaF. therinfections, caused *y such pathogens as ?erpes 0imple+ myco*acteria, yeasts, ?erpes 3oster,o+oplasma, ytomegalovirus are also common.
he most common tumors developed in $I&0 are: AaposiHs sarcoma and lymphomas. AaposiHssarcoma typically produces one or more reddish purple nodules on the skin, 9isceral involvement'ith AaposiHs sarcoma in $I&0 is also common.
#on!?odgkinHs lymphomas, essentially <urkitBs lymphoma is usually seen in $I&0.
$ccording to prevalence of clinical appearances in organs systems, there are the follo'ing clinicvariants of $I&0:
• Pulmona"y 'o"m 6<=>7(• Ce"e "al 'o"m(
• ;ast"o)intestinal 'o"m(
• Fe$e" o' un1no?n etiology .
RIC0ETTSIAE
"ickettsiae comprise a group of microorganisms that phylogenetically occupy a position *et'een *acteria and viruses. hey are o*ligate intracellular gram!negative cocco*acillary forms that multiply
'ithin eukaryotic cells."ickettsiae are a rather diverse collection of organisms 'ith several differences. $ generalcharacteristic of rickettsiae is that mammals and arthropods are natural hosts. "ickettsioses areusually transmitted to humans *y arthropods.
he epidemiology of human diseases caused *y rickettsiae is intimately related to the *iology of thevector that transmits it. "ickettsial diseases 'idely vary in severity from self!limited mild illnesses tofulminating life!threatening infections.
"ickettsial illnesses, caused *y organisms 'ithin the genus of rickettsiae, are recogni3ed and can *edivided into the follo'ing 6 *iogroups:
• Sc"u ty!hus iog"ou! 6Tsutsugamushi #isease7: he 6 ma;or serotypes are Aarp, Gilliam,and Aato.
"ickettsiae microorganisms appear to e+ert their pathologic effects *y adhering to and theninvading the endothelial lining of the vasculature 'ithin the various organs affected. he adhesinsappear to *e outer mem*rane proteins that allo' the rickettsia to *e phagocytosed into the host cell.nce inside, the rickettsial organisms either multiply and accumulate in large num*ers *efore lysingthe host cell (typhus group) or they escape from the cell, damaging its mem*rane and causing theinflu+ of 'ater (spotted fever group).
"ickettsiae rely on the cytosol of the host cells for gro'th. o avoid phagocytosis 'ithin the cells,they secrete phospholipase & and hemolysin , 'hich disrupt the phagosomal mem*rane, allo'ingfor rapid escape.
he most important pathophysiologic effect is increased vascular permea*ility 'ith conse=uentedema, loss of *lood volume, hypoal*uminemia, decreased osmotic pressure, and hypotension. nthe other hand, disseminated intravascular coagulation is rare and does not seem to contri*ute to the
pathophysiology of rickettsiae.
EPI5EMIC TYP8*S
-ouse!*orne typhus is the more fre=uent rickettsiosis. his is anthroponosis and transmitted *y%ediculus humanus, the *ody louse. he head louse does not transmitthis infection.Pathogen& "ickettsia pro'a3ekii.E!i#emiology& ?umans are the reservoir for ".pro'a3ekii, and infection passes from one person toanother as the lice pass *et'een people.1pidemic disease occurs 'hen infection is introduced into a large group of people not previouslye+posed. hese are usually relatively poor, displaced people cro'ded in unsanitary conditions."efugee camps present an ideal situation for such epidemics.1pidemics have occurred in 1urope, $sia, and $frica. $frican countries, especially 1thiopia and
#igeria.8ale gender more prone to epidemic typhus.Pathogenesis& $fter taking a *lood meal the louse defecates,and ". pro'a3ekii in the faeces of aninfected louseis scratched into the *ite site or a*rasions in the skin.hese organisms replicate 'ithin vascular endothelial cells of small vessels, especially in capillaries
in many organs and tissues.-eakage of protein!rich fluid from the vascular compartment into the interstitium causeshypovolaemia, hypotension and reduced tissue perfusion. tic lesions he vascular lesions 'iththrom*osis can affect all organs2 they most readily are found in the skin, adrenals, #0, heart, liver,especially in severe cases. 9asculitic responses and *lood vessel damage underlie the pathogenesis and clinical presentations.he effect of *lood vessel damage is a "ash that may *ecome purpuric and haemorrhagic, evenecchymotic.
-ymphocytes phagocyted the 'eakened pathogens as Fimmunological memory cellsF remain inlymph nodes and supply the immunity for a long time. Immunity disappears 'hen these lymphocytescan *e destroyed. "ecidivation of disease lead to appearance of <rill!Jinsser disease i.e, relapsing
$ccording to clinical course there are subclinical, severe, medial, mild and ulminant forms ofdisease.Incu ation !e"io# lasts usually a*out ! 5 days. ?eadache and mild fever are the usual initialsymptoms, follo'ed after 5K hours *y a sharp rise in temperature to 5>L , 'hich is sustained.on;unctival suffusion is seen. 8eningism and photopho*ia also occur.
he vascular changes are common in skin and medulla o*longata.
<iopsies sho' evidence of throm*osis and necrosis of capillaries, as 'ell as perivascularmononuclear cell infiltration.$s the vasculitis consists of 6 components: throm*osis, necrosis and cellular proliferations. &ue to
prevalence of any component, there are the follo'ing types of vasculitis:• 1ndothrom*ovasculitis2• %roliferative vasculitis2• #ecrotic vasculitis2• 8i+ed vasculitis.
Cocal areas of endothelial proliferation and perivascular mononuclear cell infiltration causeformation of e!i#emic ty!hus g"anulomas&
1pidemic typhus granulomas of skin lead to formation of rashes. he rash occurs on a*out the th day and *egins as red macular lesions on the a+illary folds andtrunk, spreading on to the lim*s, 'ith the palms, soles and face affected in the most severe cases. herash may evolve through purpuric stages to form ecchymoses.
$n addition of menongoencephalitis, a #eli"ium , i.e. a state of e+citement and mental confusion,accompanied *y hallucinations occurs. he proliferative interstitial myocarditis, 'ith acute heart insufficiency may develop.
Initial *radycardia progresses to tachycardia in hypotensive patients. ?aemorrhagic manifestations and hypotension lead to renal involvement, 'ith rising *lood urea andfalling urine output.
8ild cases get *etter in the second 'eek of the disease, *ut severe cases may go into the third 'eek
*efore recovery *egins.Com!lications: 8yocarditis, heart insufficiency,cere*ral involvement, throm*ophle*itis, real
failure, secondary purulent inflammation focuses, gangrene 'ith loss of fingers and toes etc. mayappear.5eath from shock, cere*ral involvement , heart insufficiency or renal failure occurs in the second orthird 'eek.Mo"tality "ates in untreated cases correlate 'ith the patientHs age. he mortality rate isappro+imately >/ in young adults *ut approaches >!M>/ in patients older than 7> years.
his is acute infectious disease. $lthough may occur in any age group, it usually affect children.his is typical anthroponosis: the reservoir of infection is an infected human (patient and *acteria!carrier).Pathogen : Neisse"ia meningiti#es or meningococcus or #i!lococcus .Pathogenesis: he pathogen is spread *y droplet infection. he entry of infection is upper respiratorytract, especially nasal and pharyngeal mucosa, 'here it can cause a nasopharyngitis in >! 7/ ofcases. 1ndoto+in released *y meningococcus causes disorders of coagulation system, to+ic microvascularin;ury, necrosis of endothelium and fi*rinoid necrosis of vessel 'all. <iogenic amines, also produced
*y action of endoto+in, lead to degeneration and necrosis in different organs and tissues.?yaluronidase released *y the pathogen, causes an increasing of permea*ility of vessels and tissuemem*ranes.
?yaluronidase allo's *acteria to pass through mem*ranes into *lood, and cause a *acteremia.Immune!supression (in >,7! / of cases) may lead to the penetration of hemato!encephalic *arrierand meningitis develops.
$s the hemato!encephalic *arrier of children younger 7 years old, is not completely formed, theyare much more suscepti*le to meningeal involvement. $long 'ith hematogenous mechanism,
*acteria can reach the *rain *y transmission of *acteria from ear or nasal suppurative inflammation inthe su*arachnoid space of the *ase of the *rain.
&irect infection may occur secondarily, *y the penetrating craniocere*ral trauma. helymphogenic spreading is also supposed. In e+tremely de*ilitated persons, generalisation of infection ! meningococcal se!sis –Meningococcemia develops. o+emia is superimposed to *acteremia. 8eningococcal endoto+in cancause paralytic dilation of capillary vessels, stasis, diapedesis, throm*osis and micro!infarcts.8eningococcal sepsis is usually manifested in the form of septicopyemia. he most severemanifestation of meningococcal sepsis is 'ulminant meningococcemia , 'hich is usually fatal.o+emia may lead to lethal complications, as cere*ral hypertension and cere*ral edema.Clinical !"esentation: In spite of clinical!morphological polymorphism the most fre=uentmanifestations of meningococcal infections are the follo'ing: 9& Meningococcal naso!ha"yngitis%& Pu"ulent meningitis% & Meningococcemia&Incu ation !e"io#: appro+imately 'eek and can *e follo'ed *y nasopharyngitis.
MENIN;OCOCCAL NASOP8ARYN;ITIS or acute nasopharyngitis, usually harmless diseaseof the respiratory tract, and is characteri3ed *y catarrhal mucinous!purulent inflammation. he nasalmucosa and the dorsal pharyngeal 'all is congested, edematous, lymphoid follicles are hyperplastic.here is lympho!leukocytic infiltration of mucosa and su*nucosa. &isease lasts for 'eek.P*R*LENT MENIN;ITIS ! suppurative inflammation of the central nervous system 'ith focalmanifestation in the meninges. 8eningitis may follo' nasopharyngitis, or can develop
primarily.Infection 'ith #eisseria meningitidis triggers suppurative inflammation in thesu*arachnoid space primarily through the conve+ities, producing a hood!like pattern of metastaticmeningitis. he inflammation spreads to ad;acent *rain tissue, resulting in causingmeningoencephalitis.Sym!toms occur due to involvement of the central nervous system: nausea and vomiting, fever,
severe headache, sensitivity to light ! photopho*ia are present in almost all the cases. thermeningeal symptoms are neck stiffness (from irritation of spinal nerve roots), and cloudedconsciousness ! stupor, tonoclonic spasms also occur.
8icroscopic e+amination: at the *eginning of disease the process of a serous character. 0everal dayslater a neutrophilic e+udate involves the meninges, vessels are prominent dilated, 'ith the *rainedema. Ci*rinous e+udate also may mi+ and fi*rinous!purulent inflammation appears.
Inflammation of pia mater is termed as le!tomeningitis . If inflammation involves the dura mater !!achymeningitis develops. Involvement of the *oth meninges is called as meningitis . heinflammation may reach the *rain tissue ! meningoence!halitis , and *rain ventricles and central
canal of cord! e!en#ymitis .In practice leptomeningitis is fre=uent. &uring the meningoencephalitis due to increasing of permea*ility of vessels there are multiplediapedesis, i.e. hemorrhages and degenerative changes of *rain tissue.&ue to edema and thedescri*ed a*ove changes of *rain tissue meningoencephalitis usually fatal.Com!lications: "esolution of purulent inflammation occurs completely, *ut fi*rinous mass may *efollo'ed *y adhesive arachnoiditis 'ith o*literation of su*arachnoid space leading to distur*ances ofcirculation of cere*ro!spinal fluid, 'ith o*structive hydrocephalus or epileptic spasms.MENIN;OCOCCEMIA is the meningococcal sepsis, may follo' nasopharyngitis or associated'ith meningitis. his type of sepsis is characterised *y to+emia and proper clinic symptoms,secondary purulent focuses. In all organs and tissues there are the generalised microvascular in;uries !vasculitis and perivascular diapedesis ! petechial rash. -ater symptoms and signs can include: hanging level of consciousness, shock, large areas ofhemorrhage and throm*osis under the skin, &I (a severe *leeding disorder), necronephrosis andadrenal collapse all predispose the patient to a poor prognosis 'ith possi*ility of a death.
&evelopment of sepsis occurs *ecause of depression of immune system, hypersensitive reaction of *ody to antigens of pahogen. Com!lications are: &isseminated intravascular coagulopathy (&I )and throm*osis, to+ico!allergic shock , serous or purulent arthritis , suppurative pericarditis , profuse
*leeding into tissue and diffuse cutaneous hemorrhage in the form of suggillations of ecchymoses –e+anthemas, *ilateral hemorrhagic adrenal necrosis leads to acute hypocorticism ($ddisonBs crisis)'ith electrolyte im*alance and spontaneous hypoglycemia. he latter is called &aterhouse'(riderichsen Syndrome. here are the follo'ing clinical forms of meningococcemia: acute and chronic. $ccording thecourse acute meningococcemia may *e of lo) !, middle !, high severity and ulminant . Culminantmeningococcemia leads to death due to cardiovascular insufficiency, acute renal insufficiency andshock.
5IP8T8ERIA
&iphtheria is a *acterial droplet infection. his infectious disease may affect human of any age, *utusually occurs in children till M. It is a typical anthroponosis and is characterised *y the formation offi*rinous inflammation of upper respiratory 'ays, to+emia, to+ic in;uries of cardiovascular, and
nerve system.Pathogen: Gram!positive rods ) Co"yne acte"ium #i!hthe"ia& he entry of *acteria is nasal, pharyngeal and tracheal mucosa. 1+oto+in ela*orated *yco"yne acte"ium% can penetrate the *loodstream and causes all clinical and morphologicalmanifestations, as cytopathic, vasoparalytic and neuropathic changes. 1+oto+in primarily damagesthe heart, microvascular system, nerves and adrenals.Pathogenesis: he pathogenBs e+oto+in causes irreversi*le *lockage of cellular protein *iosynthesis.his leads to cell death, tissue necrosis, and fi*rinous pseudomem*ranous necroti3ing inflammation,'hich is characteri3ed *y formation of 'hitish!greyish pseudomem*rane on the mucosa. hethickness of this mem*rane depends on type of epithelium (stratified or one!layered) and depth ofnecrosis.
Incu ation !e"io#: ! > days.Clinical !"esentation and mo"!hology is differ and dependes on locali3ation of inflammation.here are t'o clinical!morphological forms of diphtheria:
9& 5i!hthe"ia o' !ha"yn.(& 5i!hthe"ia o' u!!e" "es!i"ato"y t"act&
5i!hthe"ia o' !ha"yn.
Pathogenesis: $s the pharyn+ is lined *y stratified s=uamous epithelium the inflammatory necrosise+tends to the su*mucosa, causing erosion of the su*mucosal vessels and resulting in the escape offi*rinous e+udate over a 'idearea. he e+udate spreads over the surface of the mucosa, forming a #i!hthe"ic !seu#omem "ane'ith root!like adhesions in vascular *ranches of the su*mucosal tissue. his causes *leeding 'henthe pseudomem*rane is forci*ly removed. In this form the local and general changes are evident.
• *ocal changes occur on throat, pharyn+ and tonsils. he regional lymph nodes are painful,congested, edematous and necrotic, 'ith the hemorrhages.• +eneral changes include: to+emia and changes of internal organs, especially heart, vessels,nerves, kidneys and adrenals.
8ea"t : to.ic inte"stitial myoca"#itis develops. here are lympho!leukocytic infiltration, hyperemia,edema in perivascular spaces and myocardial interstitium. 8yocardiocytes undergo to
parenchymatous proteinaceous, and fatty degenerations,myolysis. ?eart cham*ers are dilated, softand opa=ue. hese changes may lead to death, at the *eginning of the second 'eek of the disease,due to acute heart insufficiency, 'hich is called /Ea"ly hea"t !a"alysis/& "ecovery is resulted indiffuse cardiosclerosis.Ne"$e system involvement is characterised *y changes of peripheral nerves and vegetative ganglialocalised in neck, i.e. nodous ganglion of n.vagus, ganglion stellate, facial, vagal, glossopharyngeal,
phrenic and intercostal nerves. #erve cells undergo to degeneration, karyolysis, karyorhe+is. In peripheral nerves Pa"enchymatous neu"itis develops. he lesions are perivascular *ut they e+tend
to the sheath, giving rise to damages the surrounding myelin and a+ons , i.e. a characteristic 3one of'ell!marked demyelination of nerve fi*res. his is follo'ed *y paralyses of dependent muscles in,7! month. &ue to impairment of heart innervation, the patient may die 'ith acute cardiacinsufficiency ! /Late hea"t !a"alysis/&0i#ney : nec"one!h"osis ! necrosis of epithelium of pro+imal and distal convoluted tu*ules occurs.linically it is manifested *y acute renal insufficiency.A#"enals: in medulla hyperemia, diapedesis is evident. ells in *oth ! corte+ and medulla, undergoto degeneration and necrosis. $drenalin synthesis is destroyed, leading to collapses.Com!lications are divided in t'o groups: speci ic and non'speci ic .• Speci ic complications include: myocarditis, polyneuritis, early and late heart paralysis, peripheral paralysis, to+ic shock, nephrotic syndrome, acute renal insufficiency etc.
• %on'speci ic complications include: pneumonia, otitis, lymphadenitis etc., due to superimposedsecondary infections.
5i!hthe"ia o' the u!!e" "es!i"ato"y t"act
In this form of Infection lesions are localised in laryn+, trachea and large *ronchi. his is aninfre=uent form, and usually affects the infants ( !7 years).he disease is characterised *y evident local signs. General to+ic changes are uncommon.Pathogenesis : Initially there is only serous inflammation, 'ith hyperemia, edema, lymphocytic and
plasmacytic infiltrationof the mucosa. he respiratory tract is lined *y the one!layer cylindric epithelium, and in;ury involvesonly upper part of mucosa. his is follo'ed *y a 'ide area of fi*rinous e+udate on the *asementmem*rane of the largely de!epitheliali3ed mucosa, 'ith the formation of a grayish!'hite c"ou!ous
pseudomem*rane that can *e easily removed 'ithout *leeding.
Clinical !"esentation: he disease *egins as nasal diphtheria and spreads to the laryn+, trachea, and *ronchi, 'ith development of easily removed pseudomem*rane, 'hich can *e detached duringcoughing and is clinically manifested as C"ou!&
he lesion in laryngeal diphtheria is genuine c"ou!& linically it is an inflammatory stenosis of thelaryn+ 'ith shortness of *reath, a 'histling sound during inspiration ! st"i#o"% a loss of voice )a!honia and a / a"1ing/ cough.
hese inflammatory lesions may e+tend do'n'ard to the lo'er respiratory 'ays, 'ith developmentof pneumonia ! F #escen#ing c"ou!/ .Com!lications include as!hy.iation% 'hich can re=uire an emergency tracheotomy . <acterialsuperinfection due to this procedure in the form of suppurative perichondritis, phlegmon ormediastinitis may also happen. $long 'ith the descri*ed a*ove t'o forms of diphtheria, there may *e the least fre=uent forms ofdisease ! diphtheria of ear, eye diphtheria, 'ound diphtheria, um*ilical diphtheria of ne'*orn etc.
SCARLET FEVER
Sca"latina is an acute childhood infectious disease, and commonly affects children 6!M years old.It is typical anthroponosis. Illness usually *egins 'ith a fever and sore throat. It may *e accompanied
*y chills, vomiting, a*dominal pain, malaise, lymphadenitis and general to+emia.Pathogen: group $ *eta!hemolytic streptococci.E!i#emiology: he reservoir is the infected person. <acteria are spread *y direct contact 'ithinfected persons or *y droplets e+haled *y an infected person. $fter recovery the anti!*acterial andanti!to+ic immunity is conferred.Incu ation !e"io#: 7 to days.Pathogenesis: 1ntry for *acteria is throat and tonsils, 'here *acteria can *e fi+ated and proliferatecreating to+ins. $ll the follo'ing to+ic manifestations of disease are developed, *ecause of theseto+ins. he erythrogenic to+ins damage capillary 'alls and cause hemolysis, producing patchyerythematous rash on the skin ! e.anthema .Clinical !"esentation is developed in t'o consecutive periods:
• P"ima"y !e"io# occurs in second 'eek of disease, and develops due to action ofstreptococcal to+ins. his period is characterised *y local and general pathological changes.• Secon#a"y !e"io# develops in 6!7 'eeks of disease, and occurs due to sensiti3ation oforganism *y to+ins and destruction products of *acteria. hese immune!pathological changes canlead to vasculitis, acute and chronic glomerulonephritis, polyarthritis, endocarditis, otitis etc.
$t the entry site of *acteria develops firstly ! catarrhal , then the necrotic tonsillitis, 'hich is termed!"ima"y sca"latinal a''ect or !"ima"y sca"latinal 'ocus . Inflammatory process e+tends to attachedlymph vessels ! lym!hangitis and regional lymph nodes ! lym!ha#enitis . $s a result the !"ima"ysca"latinal com!le. is formed.
If the *acterial entry is localised in the other site (lung, 'ound,endometrium etc) this form istermed as e.t"a uccal scarlatina. $cute hyperemia and congestion giving rise to a red and *right coloration of throat ! F 'lamingth"oat/% then can e+tend to pharyn+, tongue ! /st"a? e""y/ tongue, middle ear and esophagus. In afe' days necrotic changes on tonsils ! necrotic tonsillitis appear. n esophageal and gastric mucosaerosions are formed. "egional lymph nodes *ecome inflamed ! lymphadenitis. he gene"al changes appear due to to+emia. he streptococcal to+in causes a "ash) e.anthema thatappears one to t'o days after the onset of illness. he rash usually first appears on the neck andchest, then spreads over the *ody. It is descri*ed as /san#!a!e"y/ in =uality. Ehile the rash is stillred, on the patientHs *ody may appear:Filato$2s t"iangle ! the pale area 'ithout rash *et'een nose and nasola*ial folds, resem*lingtriangle
PastiaBs lines ! *right red coloration of the creases under the arm and in the groin. he rash can lastfor up to !6 'eeks *efore it is fully resolved. $s the rash fades, peeling (des=uamation) may occuraround the finger tips, toes, and groin area.
8icroscopic e+amination reveals edema and perivascular lympho!histiocytic infiltration. Inepidermis there is local hyperemia, parakeratosis. In !6 'eeks necrosis and des=uamation develop.
?eart, kidney and liver are most fre=uently affected, 'ith parenchymatous proteinaceous and fattydegenerations, interstitial to+ic inflammation. -ymphoid organs and nerve system can also *einvolved.
$ccording to clinical course 0carlatina may *e of mino"% me#ial and ma o" severity. 0carlet feverof a mino" severity is the most fre=uent, characterised *y the only local changes. 0ore throat 'ithoutnecrosis, lasts for 5!7 days. "ash fades in 6!5 days.
0carlatina of me#ial severity occurs in 6>/ of cases. $ll the descri*ed a*ove local and generalchanges are o*viously indicated.he disease of a ma o r severity is rare no'adays, due to anti*iotic therapy. $ccording to pathogenicmechanism this form develops in 6 variants:
• Severe toxic scarlatina. he most severe form, is characterised *y to+emia, may lead to deathin !6 days.
• Severe septic scarlatina occurs in de*ilitated patients (usually in children),is manifested assepsis, 'ith multiple purulent focuses in organs and tissues. here is hyperplasia of lymphoidtissue and splenomegaly.
• Severe mixed scarlatina is characterised *y to+ic and septic changes.
&ifferential diagnosis of ulcers of the small *o'el should distinguish *et'een typhoid ulcers, 'hichdevelop along the longitudinal a+is of the *o'el, and transverse tu*erculosis ulcers.
5YSENTERY
<acterial dysentery is the acute *acterial infection, affecting the distal part of large intestine, i.e.rectum, sigmoid sometimes the lo'er part of colon. his is the strict anthroponosis.Pathogen: Shigella #ysente"ia&
E!i#emiology& ut*reaks of shigella dysentery is associated 'ith poor sanitation, inade=uate 'atersupplies, contaminated food, cro'ded living conditions.
Pathogenetic 'acto"s: 0higella can adhere and penetrate the colonocytes *y surface antigens andendoto+in, 'hich is a part of the lipopolysaccharide comple+ integrated into the *acteriumBs outermem*rane. 0higella also can ela*orate enteroto+in, 'hich has the cytoto+ic, enteroto+ic,
vasoparalytic and neuroparalytic action. &ue to cytoto+ic activity colonocytes can *e destructed andulceration occurs.
1nteroto+in causes an increasing of secretory activity of intestine. 9asoparalytic action leads toincreasing of permea*ility of vessels and inflammatory infiltration of intestinal mucosa, resulting infi*rinous colitis. #europaralytic action causes the destruction of intramural nerve ganglia of *o'el.Incu ation !e"io# is an average of 6 days.$ccording to clinical manifestations there are the follo'ing forms of dysentery:A& Acute #ysente"y develops in a several variants:
• Colitis ! typical dysentery 'ith colitis and to+emia.• ;ast"oente"ocolitis is characterised *y the superadding of gastritis and enteritis to previous
form.• ;ast"oente"itis ! this variant occurs 'ithout colitis. he last t'o variants are the atypical
dysentery.-& Ch"onic #ysente"y is characterised *y recidivations and remissions2
C& Su clinic #ysente"y ! this is the *acterial! carriage condition.$ll morphological changes are su*divided into groups: Local and gene"al&Local mo"!hological changes usually occur in large intestine, i.e. in rectum!proctitis, and insigmoid colon – sigmoiditis. hese changes develop in 5 stages:9& Cata""hal colitis(& Fi "inous colitis(
& *lce"ati$e colitis(& Reco$e"y .Cata""hal colitis& linical manifestations are characterised *y colitic syndrome %(consisting offre=uent *o'el movements ! diarrhea 'ith cramps or colicky a*dominal pain , pain on defecationtenesmus), and toxemia (including neurologic symptoms, high fever etc). $nti*iotic therapy maylead to recovery at this stage, 'ithout passage to the follo'ing stages. 0uch manifestation is calledthe abortive orm of dysentery.Fi "inous colitis or #i!hthe"ic colitis is characterised *y formation of pseudomem*rane over theepithelium. Inflammation reaches the intestinal su*mucosa, destroys the epithelium of the crypts,
#ecrosis spreading to the su*mucosal vessels, results in fi*rin permeation and demarcation *yleukocytes. he e+udate spreads over the surface of the eroded mucosa, forming a diphtheric
pseudomembrane 'ith root!like adhesions in vascular *ranches of the su*mucosal tissue. his causes *leeding 'hen the pseudomem*rane is *eing removed during intestinal movements. Intramural nerve ganglia are destroyed as 'ell, 'hich can *e manifested as spastic colitis. his stagelasts 7! > days, and passes to conse=uent stage.*lce"ati$e colitis develops in >! days. 8ultiple ulceration occur in the intestinal 'all, due todemarcation and removing of necrotic tissue during peristaltic movements. $s the pseudomem*raneis of diphtheritic character, sloughing of this thick mem*rane leads to multiple hemorrhages, even to
perforation of intestinal 'all. linically this stage is manifested *y *loody stools.Reco$e"y stage *egins at the end of second 'eek and lasts 'eeks. "estitution and su*stitutionoccur. 0mall and superficial ulcers can *e *eing completely recovered. &eep lesions are replaced *yscar. &iffuse sclerosing can result in cirrhosis ! the narro'ing and deformation of intestine.$long 'ith ty!ical changes, descri*ed a*ove, aty!ical changes also may occur. 1.g. in immune!depressive patients. anaero*ic flora may *e superimposed to the dysentery and gangrene of intestinemay develop. 0ometimes the e+ogenic and endogenic factors, such as immune deficiency,hypovitaminosis, inade=uate treatment or secondary infections lead to delayed recovery and lastsmore than 'eeks. his condition is characterised *y formation of pseudopolipi, patchy atrophy anddeformation of crypts of the colonic mucosa. 0ome scientists term these changes as ch"onic#ysente"y .;ene"al mo"!hological changes occur in other tissues and organs, due to circulation of shigellato+ins in *lood. $ll these disorders are non!specific. General morphological changes in dysentery aresu*divided into t'o groups:
9& 8y!e"!lasia o' lym!hoi# tissue !enlargement of spleen, mesenteric and regional lymph nodes.8etaplasia of lymphoid tissue and lymphadenitis is common2& 5egene"ati$e an# nec"otic changes in o"gans: $long 'ith parenchymatous lipid degenerationof heart, liver and kidneys, there are small necrotic focuses in liver and kidneys. he sympathetic
paraverte*ral ganglia also undergo to degenerative changes. &ehydration and disorders of electrolyte *alance is characteristic for chronic dysentery.
Com!lications may *e /ntestinal and extra'/ntestinal :• /ntestinal complications : most of them occur in ulceration stage ! phlegmona of intestine, *leeding, perforation, peritonitis, paraproctitis, to+ic dilation of intestine2 other complications canoccur after recovery stage ! e.g. cirrhosis of large intestine. #o'adays intestinal complicationsdevelop rarely.• 0xtra'intestinal complications$ to+ic and dehydration shock, secondary infection leads to tu*ulo!interstitial nephritis, pyelitis, pyelonephritis, pneumonia, otitis, pyelonephritis, liver a*scesses,secondary amyloidosis in chronic dysentery etc.
holera is an acute =uarantine infection. his is a strict anthroponosis, 'hich characteri3ed *ysevere dehydration of patient due to 'atery diarrhea and vomiting. holera occurs in epidemics 'henconditions of poor sanitation, cro'ding, 'ar are present. 1ndemic areas include some regions of
India, $sia, $frica, the 8editerranean, entral $merica, and 8e+ico.Pathogen: Vi "io chole"ae ! short!curved Gram!negative, rod! shaped *acteria.E!i#emiology& holera is highly contagious infection. ?umans are the reservoir of the pathogen.he pathogen is transmitted in contaminated or untreated drinking 'ater and food, and multiplies inthe lumen of the small intestine ! duodenum. $nti!to+ic immunity is ac=uired after recovery.Pathogenesis: he *acteria ela*orate to+ins, 'hich cause increased secretion of 'ater and chlorideions in the intestine, producing massive diarrhea *y the follo'ing mechanisms: here the <component of its enteroto+in ! chole"agen allo's it to adhere to the intestinal enterocytes. he $component of the cholera enteroto+in invades the cell 'here it activates adenylate cyclase,stimulating chronic production of c$8%. his in turn results in permanent protein kinase stimulation,successively leading to chronic opening of the ion channels and e+cessive passage of electrolytes and'ater from the enterocytes into the lumen of the *o'el.Clinical !"esentation : %atients present 'ith diarrhea and vomiting. Cecal discharge is cloudy and'atery, contains massive =uantities of pathogens, and reaches a volume of up to > l per day.
ehydration or exicosis , also e+cessive loss of electrolytes can occur. #ypovolemia %hypotension,hypothermia, microcirculatory disturbances, tissue hypoxia, anuria, uremia and shoc follo'.$ccording to the proportion of lost fluid, there are 5 degree of dehydration:I degree ( !6/)2 II degree (5! /)2 III degree (N!4/) and Iv degree (more 4/). $ccording tointensity of clinical appearances, there are 6 forms of cholera: lo', medial and high severity. hereare 6 stages of cholera:9& Stage o' chole"ic ente"itis(& Stage o' chole"ic gast"o)ente"itis(& Algi# stage&Chole"ic ente"itis is characteri3ed *y serous inflammation of small intestine, 'ith congestion,edema, punctual hemorrhages and inflammatory infiltrastions of mucosa, hydropic degeneration ofcovering and glandular epithelium. 1nteritis appears 'ith diarrhea and dehydration of Odegree.Chole"ic gast"o)ente"itis& $long 'ith enteritis catarrhal inflammation occurs in stomach. 9omitingis superadded to the diarrhea (up to 7! > times per day) and aggravate the dehydration (II degree). 8icroscopic e+amination reveals catarrhal inflammation and hydropic degeneration of smallintestine and stomach.Algi# stage . Increasing of *lood viscosity and hypovolemia lead to hypothermia ! decreasing of
*ody temperature (67 >!65 > ). &ehydration *ecomes severe (III ! Iv degree).
&eath can result from the severe dehydration *rought on *y the diarrhea.Sym!toms:
• #ippocratic ace ! the sallo' facial e+pression, 'ith listless staring eyes, often regarded asdenoting approaching death2• +lassy or sun en eyes , no tears
• *ethargy ! unusual sleepiness or tiredness 2
• 0kin and mucus mem*ranes *ecome dry. he skin lose its normal turgor and elasticity. &ry skinsag *ack into position slo'ly 'hen pinched up into a fold *y the doctor - holeric olds 2 0kin ofhands *ecomes dry, pale and 'rinkled – -*aundress5s hands .
• ther symptoms are e+cessive thirst, lo' urine output, a*dominal cramps, rapid pulse and heartrate, convulsions, aphonia, shock.
$lgid stage is usually fatal.Com!lications can *e specific and non!specific.• S!eci'ic com!lications: choleric typhoid and post!choleric uremia. holeric typhoid can developin de*ilitated patients, characterised *y diphtheritic colitis, typhoid e+anthemas, and septic changes.
Post'choleric uremia occurs due to multiple necrosis or infarctions in cortical layer of kidney.• Non)s!eci'ic com!lications include uremia, acute renal insufficiency, coma, shock andsecondary infections (pneumonia, a*scesses, sepsis etc.). &eath is usually caused *y severe dehydration and complications. 1+amination of corpses of
patients in autopsy reveals: orpse rigor appears rapidly after death and lasts longer. Cle+ors areinvolved more than e+tensors, and *ody get a gladiator posture . $ll changes occuring in algidstage remain after death also: F #ippocratic ace F!, +lassy eyes , - holeric olds 2-*aundress5shands etc. -ivories are pale and form later. 0kin, serous and mucosal surfaces are dry. In contrast to otherinfections, spleen is shrunken, 'ith 'rinkled capsule. Internal organs undergo to proteinaceous andlipid degeneration, necro*iotic and necrotic changes. $s the liver fail to produce *ile, gall *laddercontains translucent *ile ! /?hite ile/& Aidney is also shrunken, capsule is easily stripped, necroticnephrosis develops. <lood in the vessels is reduced and viscous. here is a less mucoid fluid *et'eenthe intestinal loops. In the gut lumen the fluid of a rice )ater appearance 'ith FfishyF odor isseen.
T*-ERC*LOSIS
u*erculosis is the chronic infectious disease. It is characteri3ed *y formation of caseousnecrosis and granulomatous inflammation around the lesion, i.e. tu*erculous granuloma ) tu e"cleappears.
u*erculosis is related to group of “ S!eci'ic in'lammation . It remains prevalent indeveloping countries, affecting *oth children and adults of *oth gender.
Pathogen& 8yco*acterium tu*erculosis (tu*ercle *acillus: .<.), an organism 'hich has aresistant 'a+y component in its structure, and is acid and alcohol fast. here are 5 types of <:P ".#ominis or ". uberculosisP ".!ovisP ".6viumP "./ntracellulare
8. u*erculosis and 8.<ovis are pathogenic for humans.u*erculosis has the several peculiarities:
P u*erculosis is u iGuitous or common in'ection(P linic manifestations are differ, depending on immunological status of organism2P hronic disease, 'ith the alternation of e+acer*ation and remission phases.
E!i#emiology& u*erculosis transfers mostly as air!droplet infection. he patient and carrier persons are the reservoir of disease. he lungs are more commonly affected *y tu*erculosis than anyother organ. u*erculosis is common infection usually in childhood. In advanced countries 'here theincidence is lo'er the initial lesions of tu*erculosis may *e delayed until adult life and certainly theserious forms of this disease are usually found in older individuals.
-ess commonly an individual catches the infection *y alimentary 'ay (*y the contaminatedfood and milk), 'ith the locali3ation of primary tu*erculous focus in distal part of ileum. "arely <may enter *y the other 'ays: tonsils, skin lesion, placenta.
SeGuence of development of granuloma: 9. ! days ! occurs infiltration *y !olymo"!hs .& In a 'eek polymorphs are replaced *y mac"o!hages .& In 'eeks macrophages are converted to e!ithelioi# cells ! elongated and arranged around
central focus of caseous necrosis, producing a tu*ercle.he granuloma consists of caseation at the centre, surrounded *y ! -ymphocytes, -anghans
giant cells, epithelioid cells, Q fe' collagen strands.$ccording to pathogenetic, clinical and morphological peculiarities, there are three forms of
tu*erculosis:P P"ima"y tu e"culosisP 8ematogenic tu e"culosisP Secon#a"y tu e"culosis
PRIMARY T*-ERC*LOSIS
@sually seen in non!immune children in first contact 'ith tu*erculosis. %rimary site is usuallysituated at the periphery of the right lung ( 47/)2 *ut primary site may *e also occasionally in thesmall intestine (5/) or pharyn+, tonsil or skin ( /).
here are the follo'ing peculiarities of the P"ima"y tu e"culosis:P $ppears in first contact 'ith pathogen2P @sually children and teenagers are involved2P &ue to a*sence of immunity against the <, the morphogenesis is distinctive, 'ith formation of
the PRIMARY COMPLEH(P ?ypersensitivity reaction of immediate type occurs, 'ith development of e+udative and necrotic
processes at involved site2P he process is prone to generali3ation2P &uring the remission phase the para!specific changes as %onse rheumatism, develop.
Mo"!hology& "acroscopically PRIMARY COMPLEH is seen, 'hich consists of threecomponents (Cig. . ):
9& P"ima"y tu e"culous 'ocus or P"ima"y a''ect(& Caseous lym!hangitis(& Lym!ha#enitis&
P"ima"y a''ect ! the focus ( ! Rm), 'here *acilli insert the tissue2 usually the III, 9OOO, I+ andS su*pleural segments in mid!3one of right lung. "apid development of small aggregate of tu*ercles'ith caseation is formed. he elastic and reticulin fi*ers remain at this site for years. he ;8ON'ocus the final result.
Lym!hangitis : u*ercles form along lymphatic tracks, e+tending from affect to local, i.e. hilarlymph nodes, ! caseous lym!hangitis appears.
Lym!ha#enitis& "apidly the process spreads to local (hilar) tracheo!*ronchial, *ifurcationaland mediastinal lymph nodes.In gastro!intestinal tract primary affect is located in lymphoid follicles of ileum and caecum,
and seen as ulceration on the intestinal 'all2 and process spreads to mesenterial lymph nodes.
Su seGuent 5e$elo!ment $a"iants o' P"ima"y tu e"culosis&A& 8ealing 2-& Ch"onicity o' the P"ima"y Tu e"culous In'ection(C& E.tension o' the P"ima"y Tu e"culous In'ection&8ealing . his is the commonest result. 8ost commonly primary tu*erculosis is self!limited.
1+udative process is firstly alternated *y proliferative reaction, then is replaced *y connective tissue
'ith the further calcification, leaving fi*rotic small ;hon 'ocus . %roceeding calcification results inossi'ication at this site.Inflammatory reaction resolves in the follo'ing se=uence:
9& ;ene"alise# hematogenic tu e"culosis(& 8ematogenic tu e"culosis con'ine# to the lungs(& E.t"a)!ulmona"y hematogenic tu e"culosis&;ene"alise# hematogenic tu e"culosis&?ematogenic tu*erculosis is usually a generalised condition, 'ith dissemination of process
throughout the *ody. his is the most serious form of disease. In de*ilitated persons the 'ulminant
tu e"culous se!sis develops, 'hich is the fatal condition. 0ometimes spreading of process indifferent organs, 'ith granuloma production is called acute common milia"y tu e"culosis&hronicity also may occur. If lesions are larger the Common la"ge)'ocus tu e"culosis develops.
8ematogenic tu e"culosis con'ine# to the lungsIf the infection originated from 0imon focus, invades a *ranch of a pulmonary artery the
condition may *e confined to the lungs initially.ther organs are not involved, or a fe' focuses occur. @sually the lesions are more numerous
and appear in *oth lungs.$ccording to the clinical course, process may *e acute or ch"onic .&ue to the si3e of involved area, the tu*erculous focus may *e of millia"y or la"ge)'ocus type.
"acroscopically$ he lungs are intensely congested.8iliary tu*ercles, all are of roughly same si3e to mm, more numerous in the upper lo*es. $t
first translucent and grey, later *ecome larger, opa=ue and yello'. "icroscopically$ here are tu*ercles in 'alls of alveoli and *lood vessel, ad;acent alveoli
su*se=uently fill 'ith macrophages, giant cells usually a*sent. u*ercles caseate and caseationspreads to surrounding alveoli.
hronicity of process is complicated *y emphysema, pneumosclerosis and Fcor pulmonaleF !hypertrophy of right ventricle.
E.t"a)!ulmona"y hematogenic tu e"culosis&his form of hematogenic tu*erculosis is characterised *y the preferential involvement of
different organs systems. $ccording to prevalence of tu*erculous process the follo'ing forms arerecognised:
u*erculous meningitis develops in the form of le!tomeningitis , 'ith the Involvement of piamater. %rognosis is usually fatal.
he preferential sites of osteoa"ticula" involvement are: spondylitis ! inflammation ofverte*rae, gonitis ! the in;ury of knee ;oint, coxal arthritis ! involvement of hip ;oint. $s a resultdeformation of skeleton appears.
u*erculous involvement of uro!genital tract: salpingitis, prostatitis, endometritis etc.hese lesions are originated from the hematogenic disseminated focuses of primary
tu*erculosis at the same localisations.
SECON5ARY T*-ERC*LOSIS
his is a recurrence of tu*erculous infection in later life. his occurs in older children andadults 'ho have had a primary infection or have received <. .G. vaccination *y 'hich a varia*ledegree of immunity to the tu*ercle *acillus has *een esta*lished.
Pathogenesis& 'o theories have *een suggested:9& E.ogenism or Re)in'ection& his theory ($*ricosov $.I.) suggests recurrence of tu*erculous
process due to re!infection *y tu*ercle *acilli2& En#ogenism or Reacti$ation& In apparently 'ell healed tu*erculosis, tu*ercle *acilli can
survive for many years in scarred and calcified tissues and it is thought (0htelko 9.G., 0trukov$.I) that they are sa*le to re!esta*lish active disease ! "eacti$ation of the primary tu*erculosismay occur.
he evolution of the disease is much slo'er than in the primary infection. Gradually progressive disease destroys lung tissue, If the individualHs immunity is impaired for any reason.
C8RONIC CAVERNO*S T*-ERC*LOSIS occurs as a chronicity of acute cavernoustu*erculosis.#e' cavities form and coalesce to form large irregular spaces. he caseous materialmay *e completely discharged, leaving a smooth 'alled 'i "ous ca$ity&
avernous cavityHs 'all has the follo'ing 6 layers: inte"nal) caseous material of greyish to *lack color, me#ial laye" ! a granulation tissue , e.te"nal ! fi*rous tissue of 'hitish color. here is perifocal emphysematous focuses. $s the lesion e+tends, sooner or later the necrotising process 'ill
involve a larger *ronchiole or *ronchus. @sually 'hen caseous material is discharged from a chronictu*erculous cavity into a *ronchus there is no danger of *ronchopneumonia. ell!mediated immunityhas destroyed most of the *acilli and their carriers the macrophages. <ut de*ilitating of patients leadsto immune supression 'ith appearance of caseous pneumonia focuses in *oth lungs.
CIRR8OTIC T*-ERC*LOSIS . in this condition the *odyHs reparative mechanism isdominant *ut not sufficient to ensure complete healing ! a slo' progressive fi*rosis 'ith scarringresults. -ocal vessels undergo endarteritis 'ith formation of fi*rous cords. Ci*rosed arteriesfre=uently resist the caseous process and can *e seen as ridges in the 'alls of cavities.
Ci*rosis not only occurs around the cavities *ut also more diffusely throughout the lung. -ungslost the normal anatomic structure 'ith deformation and *ecome shrunken. he pleura is usuallythickened. his condition is often referred to as 'i "oi# !hthisis& .
T*-ERC*LOSIS AN5 T8E PLE*RA
Infection may spread to the surface of the lung in the very early stage of tu*erculous infection.he tu*ercles on the visceral pleura cause gross pleuraI effusion.
%leural fluid is usually clear *ut may *e 'i "inous or haemo""hagic 2 0parse lymphocytes are present as 'ell.
he effusion disappears spontaneously leaving little trace of its occurrence.In chronic secondary tu*erculosis the pleura *ecomes greatly thickened. $dhesions are
common and the pleural cavity may *e completely o*literated.
Com!lications• 8aemo""hage an# 8aemo!tysis
he *lood vessels in the tu*erculous lesions are usually o*literated *y endarteritis *utoccasionally small vessels may rupture giving rise to haemo!tysis . $neurysms may form in largervessels due to 'eakening of the 'all, rupture of 'hich may ensue 'atal haemo""hage&
• Tu e"culous ulce"s of the intestine and la"yn. sometimes result from direct infection *ysputum.
• Secon#a"y amyloi#osis of organs is a common and serious effect of chronic• Pneumotho"a.• Pleu"al e''usion• Caseous "oncho!neumonia (Cig. . )• Cache.y
0epsis (Greek: Sepsis ! supuration) ! is generali3ed infection, occurs due to specific relationship *et'een human organism and microorganism, and its development depends on virulence ofmicroorganisms (high virulence) and immune response of *ody (hypersensitivity reaction). 0epsisdiffers from other infections and has specific features.
Etiologic 'eatu"es : 0epsis – poly!etiologic disease2 may *e evoked *y all microorganisms,e+cept viruses.
Pathogenetic 'eatu"es : 0epsis doesnBt independent disease – appears secondarily ascomplication to other primary infection.
Clinical 'eatu"es: linical appearances in sepsis are similar in infections caused *y all types ofmicroorganisms. here is no e+act duration of disease. 0epsis can proceed several days or months,even years.
Mo"!hological 'eatu"es: 0epsis hasnHt characteristic morphological features2 all these changesmay occur in other infections as non!specific appearances.
E!i#emiological 'eatu"es : It does not transfer from one patient to another. It is impossi*le toreproduce the disease in e+periment.
Immunological 'eatu"es: 0epsis doesnBt confer immunity.%ortal of entry may *e in any organ or tissue. $ccording to this features there are the follo'ing
the"a!eutic (digestive system and respiratory tract), su"gical (medical manipulations), ute"inese!sis (o*stetrics manipulations), um ilical (in ne'*orn), c"y!togenic (unkno'n cause) sepsis.
Clinical classi'ication o' se!sis:• Fulminant se!sis• Acute se!sis• Su acute se!sis• Ch"onic se!sis
his is the most fre=uent form of sepsis and is haracterised *y the follo'ing peculiarities:• he most serious condition 'ith se$e"e to.aemia% shoc1 and #istu" e# immune mechanisms 2 •
8ost common in children2• %ortal of entry is unkno'n ! C"y!togenic se!sis 2• Loal changes not evident. here are not purulent metastases in tissues and organs2• ;ene"al mo"!hological changes in organs are o*vious2
o egenerations (protein and lipid),o %ecrosis ,o /nterstitial in lammations –t oc+ic myocarditis, hepatitis, pneumonia, tu*ule!
8aemo""hagic syn#"ome (skin, mucous and serous coverings, internal organs, &isseminatedintravascular coagulation syndrome)2• Clinical a!!ea"ances: $nemia, leukocytosis, ;aundice, general hemosiderosis.
SEPTICOPYEMIA
• he mild form of sepsis2• ;ene"al mo"!hological changes and into+ication not evident2• Local lesions 'ith formation of Se!tic com!le. are o*vious2• hrom*o!*acterial em*olism, 'ith se!tic in'a"ctions are common.(Cig. .5)2•
Se!tic s!leen develops2• 8ultiple purulent metastases, i.e. !yemic a scesses are seen in organs and tissues ! *rain, heart,
of septic infarction. Septic focus(usually staphylococcal
&hrombosis of "enules incorporatingbacteria
Showers of micro!emboli
'ultiple pyaemic abscesses in organs(ig.11.7 The route of Pyaemic abscesses
SEPTIC EN5OCAR5ITIS
-ACTERIAL or INFECTIO*S endocarditis is a special clinic!morphological form of sepsis.he follo'ing characteristic features are present:
• -ocal lesions occur on heart valves, commonly on aortic valves2• <acteria usually settle on previously diseased heart valves (ac=uired diseases – rheumatic fever or
pneumococcus, 1. coli, andida etc. he most common causative agent is staphylococcus aureus.he *acteria proliferate and, mi+ed 'ith fi*rin, platelets and leukocytes in varying proportions,form the large vegetations.
• 0eptic endocarditis may *e:o Primaryo Secondary
• $ccording to clinical course the follo'ing forms of septic endocarditis are marked out:
o Ch"onic$cute and 0u*acute forms are most common.
• $ccording to locali3ation three types of pathomorphological changes can *e defined:o 8ea"t changes(o Visce"al changes an# $ascula" lesions(o Pe"i!he"al changes&
8ea"t changes : commonly occur in aortic valves, 'here polypous!ulcerative endocarditis 'ithulceration and destruction of valves develop. $s a result valves *ecome sclerosed, deformationappears. %rimary endocarditis occurs on intact valves. 0econdary endocarditis appears on previouslydiseased heart valves. $long 'ith valvular changes interstitial myocarditis also appears.
Visce"al changes an# $ascula" lesions: generalised vasculitis (especially vessels of small andmedium cali*res), haemorrhagic syndrome in organs, con;unctiva and skin. Interstitial inflammationof internal organs, splenomegaly, arthritis.
Pe"i!he"al changes include:• 8ane)ay lesions are flat, painless, red to *luish!red spots on the palms and soles2• Splinter hemorrhages ! small dark lines under the fingernails2• 9sler5s nodes ' red, painful intradermal nodes in the pads of the fingers and toes2• *ibman'*u in spots ' %etechial hemorrhages on con;unctiva at the level of lo' eyelid2• rumstic or clubbed ingers;• 8aundice.
C8RONIC SEPSIS
hronic sepsis may proceed several years and is characterised *y the follo'ing peculiarity:• hronic purulent in lammatory oci in organs;• egeneration;• +eneralised interstitial in lammation and vasculitis,• 6trophy and sclerotic changes )ith lipo uscinosis;• #aemolysis, anemia, haemosiderosis o organs;• 6myloidosis;• achexia etc.
