Diagnosticul diferențial se face cu:

A. Afecțiuni toracice: nevragie, afecțiuni pulmonare, pleurale, costale;

B. Afecțiuni abdominale:
-criză ulceroasă: durere periodică în antecedente cu iradiere paravertebral stâng, ce
apare dupa o masa bogată în condimente și alimente acide, ce se atenuează în prezența
alimentelor alcaline,; ecografia și endoscopia confirmă diagnosticul.

- colică renouretrală dreaptă: prezentă în plus pe lângă durerea colicativă a tulburărilor

micționale (polakidisurie) și a modificărilor de sediment urinar cu apariția hematuriei și
cristaluriei; diagonosticul este confirmat prin radiografie sau ecografie cu evidențierea
calculilor.

-colică apendiculară: dureri în fosa iliacă dreaptă, grețuri, vărsături, constipație, ,

apărare musculară regională ce devine generalizată, care nu urmează mișcările respiratorii, plus
absența icterului.

-pancreatită acută: rareori apare independent de afectarea biliară; momentul

declanșator este același (prânz bogat în lipide), dar durerea iradiază "în bară"; diagnosticul se
pune prin determinarea amilazei și lipazei în ser și urină.

-afecțiuni hepatice: abces hepatic, formațiuni chistice hepatice, tumori hepatice etc.. Diagnostic
ecografic.

VII. Evoluția cazului

Fără tratament pacienta este predispusă la complicații precum:

 angiocolită (care poate evolua către stare septica, formarea de abcese hepatice și
insuficiență hepato-renală)
 fistule coledoco-digestive : solutii de continuitate intre coledoc si duoden, stomac,
colon, etc., cu posibilitatea apariției de ileus biliar
 inflamația sfincterului Oddi
 pancreatită acută de cauză biliară
 ciroză biliară (transformarea cirotică a ficatului în cazul obstrucțiilor coledociene
prelungite)

Tratamentul în acest caz se presupune a fi chirurgical, putându-se opta pentru mai

multe metode:
a. tratament edocsopic ERCP, urmat de colecistectomie laparoscopică sau clasică
b. laparoscopic se poate efectua colecistectomie și colenagiografie intraoperatorie
sau coledocolitotomie cu drenaj biliar extern
 c. prin tratament chirurgical clasic se poate efectua anastomoza biliodigestiva sau
colecistectomie
d. coledoctomie supraduodenală cu extracția calculilor și drenaj biliar extern sau
anastomoză biliodigestivă
Ca și risc anestezico-chirurgical trebuie să se ia în primul rând în considerare vârsta
pacientei de 76 de ani, ceea ce duce la o creștere a riscului anestezico-chirurgical prin
încetinirea procesului anabolic, tarele asociate și predispoziția la complicații in cadrul
procedurii. Prezența diagnosticului de HVC pune problema sângerării excesive în timpul
operației datorită deficienței în sinteza factorilor din cascada de coagulare și a complicațiilor
postoperatorii precum insuficiența hepatică. Dintre toate anestezicele administrate pe cale
respiratorie, halotanul și enfluranul par a reduce fluxul sangvin al arterei hepatice,
predispunând ficatul la ischemie. Halotanul este deasemenea asociat cu un grad mare de
hepatotoxicitate. Ca și agent de blocare neuromusculară se recomandă atracurium, neavând
metabolizare hepatică. Un pacient cu afectare hepatică de tipul HVC, necesită deasemenea
susținere prin corectarea coagulopatiei cu vitamină K și plasmă proaspătă pentru a aduce
timpul de protrombină la normal. Se ia în considerare și un numar de trombocite de peste 50-
100.000 și evitarea hipokaliemiei și a alcalozei metabolice, asociate cu monitorizarea riguroasă
intraoperatorie.[ CITATION Son09 \l 1048 ]
O alta patologie ce crește riscul anestezico-chirurgical este sindromul anemic al pacientei și
insuficiența venoasă cronică. Se recomanda a se corecta anemia prin transfuzii sangvine și a se
mentine o tensiune arterială sufficient de ridicată pre și intraoperator. Se recomanda
deasemenea o poziție declivă cranial a mesei de operație pentru a preveni staza venoasă
inferioară cu formarea de trombi, întru-cât nu se poate administra terapie antitrombotică
pacientei datorită coagulopatiei asociate.[ CITATION PFM93 \l 1048 ]

VIII. Terapie chirurgicala

ERCP combinat cu o colecistectomie ulterioară
1. ERCP(Coleangio-pancreatografie endoscopică retrogradă)
Înaintea procedurii pacientul va avea doar aport lichidian cu 24 de ore înaintea
intervenției. Întru-cât procedura are și scop terapeutic, se va efectua antibioprofilaxia
complicațiilor infecțioase. Medicamentele asociate patologiei cardiace sau venoase vor
fi administrate și în ziua procedurii. Anestezia pentru ERCP se va administra intravenos
pentru a produce relaxare musculară și o ușoară sedare. Se va practica și o anestezie
locală cu xilină la nivelul planșeului bucal pentru a inhiba reflexul de vomă. [ CITATION
Jay14 \l 1048 ]
ERCP-ul ca procedură de diagnostic presupune introducerea unei substanțe de contrast
radio-opace printr-un cateter prin endoscop pentru a crea radioopacitate în calea biliară
principală. Are loc pe o masă specializată de radiologie. Pentru a putea înlătura
formațiunea din calea biliară, trebuie efectuată întăi o sfincterotomie. Sfincterotomia
biliară presupune executarea unei incizii la nivelul muschiului ce inconjoară sfincterul de
deschidere a canalului coledician. Pentru înlăturarea pietrei se pot folosi diferite
balonașe și coșulețe atașate la catetere specializate ce se introduc prin intermediul
tubului endoscopului menite sa dilate CBP și să extragă calculul. [CITATION ASG \y \l 1048 ]
Complicațiile și riscurile ERCP includ[CITATION ASG1 \y \l 1048 ]:
 a. Cea mai frecventă complicație post-ERCP este pancreatita, deși deseori creșterea
enzimelor pancreatice post-procedură nu este asociată neapărat cu o pacreatită acută. Factorii
de risc pentru a dezvolta aceasta complicație sunt: antecedentele patologice de pancreatită,
vârsta, o disfuncție a sfincterului Oddi, bilirubină normală, dilatarea sfincterului biliar prin
balon, etc
b. O altă complicație este apariția hemoragiilor intraluminale sau a hematoamelor
spenice,hepatice, etc. Această complicație poate apărea atât intraoperator cât și până la doua
săptămâni după intervenție. Factorii de risc sunt: coagulopatiile( în cazul de față datorate
afectării hepatice cronice), terapia anticoagulantă administrată cu 72 de ore înainte.
c. Perforațiile din timpul procedurii
d. Infecții (colangită, colecistită) printr-un drenaj ineficient a substantei de contrast
sau a calculilor ce pot migra mai apoi
e. Alte complicații: abcese hepatice, diaree datorită antibioprofilaxiei,
pneumotorax, pneumomediastin, hematom dudenal, perforarea diverticulilor colonului, etc.

2. Colecistectomie
Hypoglycemia is a common finding. It is precipitated by fasting and strenuous exercise. 4) Muscle biopsy
reveals significant lipid vacuoles.

Treatment

Treatment of this disorder with pharmacological doses of oral carnitine is highly effective in correcting
the cardiomyopathy and muscle weakness as well as any impairment in fasting ketogenesis. All patients
must avoid fasting and strenuous exercise. Some patients require supplementation with medium-chain
triglycerides and essential fatty acids (eg, Linoleic acid, Linolenic acid). Patients with a fatty acid
oxidation disorder require a highcarbohydrate, low-fat diet.

Human Immunodeficiency Virus

HIV, the etiological agent of AIDS, belongs to lentivirus subgroup of the retroviridae family. This family of
viruses is known for latency, persistent viremia, infection of the nervous system, and weak host immune
responses. HIV has high affinity for CD4 T lymphocytes and monocytes. HIV binds to CD4 cells and
becomes internalized. The virus replicates itself by generating a DNA copy by reverse transcriptase. Viral
DNA becomes incorporated into the host DNA, enabling further replication. Besides HIV, the related
animal immunodeficiency viruses are also assigned to this group.

Structural Characteristics of HIV

HIV is a spherical enveloped virus of about 90-120 nm in diameter.(See Figure-1 below). There is a
lipoprotein envelop, which consists of lipids derived from the host cell membrane and glycoproteins
which are viral coded. The major virus coded envelop proteins are the projecting knob like spikes on the
surface and the anchoring transmembrane pedicles. The spikes, gp 120 constitute the major surface
component of the virus which binds to the cell CD4 receptors on susceptible host cells. These specific
receptors, known as cluster of differentiation- CD4 are present on certain cells in the body, the cells
possessing these receptors are called CD 4 + cells and these are -T helper cells, B lymphocytes
,macrophages, monocytes and dendritic cells. Transmembrane pedicles gp 41 cause cell to cell fusion.
Interior to the envelope is an outer icosahedral nuclear capsid shell and an inner cone shaped core
containing ribonucleoproteins.The enzymes integrase p32, protease p10, reverse transcriptase p55/66
and 2 copies of single stranded genomic RNA are present inside the core. (The proteins and
glycoproteins are indicated by their mass expressed as kilo Daltons) The reverse transcriptase enzyme is
characteristic feature of retroviruses. When the virus infects a cell, the viral RNA is transcribed by the
enzyme first in to single stranded DNA and then in to double stranded DNA (provirus), which is
integrated in to the host cell chromosome. The provirus can remain latent for long period though it
influences the host cell functions. At times in response to viral promoters, the provirus initiates viral
replication by directing the synthesis of viral RNA and other components.

88

Figure-1-A cross sectional schematic diagram of HIV virion, showing lipid bilayer in the form of viral
envelop, Nucleocapsid core, which includes a layer of a protein called p17 and an inner layer of a protein
called p24. The HIV genome consists of two copies of the single stranded RNA, which are associated with
two molecules of Reverse transcriptase p64, protease p10 and integrase p32. The outer viral proteins
are gp 120 and gp 41.

Genome of HIV

There are two types of genes analyzed,(See figure-2)

a) Structural genes encode for products which participate in formation of functional structure of virus1)
gag gene - encodes for core and shell of virus. The gene product is a precursor protein p55, which is
cleaved into p17, p24 and p15. The p24 antigen (major core antigen) can be detected in serum during
the early stages of infection till the appearance of the antibodies.

2) pol gene- encodes for the polymerase reverse transcriptase and other viral enzymes such as protease
and integrase. It is expressed as a precursor protein, which is cleaved in to components like p64 which
has reverse transcriptase and RNAse activity: p51 which has only reverse transcriptase activity: p10 is a
protease that cleaves gag precursor and p32 is an integrase.

3) env gene - determines the synthesis of envelop glycoprotein gp 160 which is cleaved into gp 120 and
gp 41 .Glycosylation occurs after cleavage. The antibodies to gp 120 are the first to appear after HIV
infection and are present in circulation till the terminal stage of infection.
89

b) Non structural and Regulatory genes 1) vif (Viral infectivity factor gene) influences infectivity of viral
particles. 2) vpr-stimulates promoter region of the virus 3) vpu(only in HIV-1 ) and vpx (only in HIV-2)
enhance maturation and release of progeny virus from cells. Detection of the type specific sequences
vpu and vpx is useful in distinguishing between infection by HIV type 1 and 2. 4) tat –( transactivating
gene) – (2 copies) having stimulatory effect on synthesis of all viral proteins . 5) rev - (Regulator of viral
genes) –(2 copies )–required for expression of structural genes. 6) nef ( negative factor gene) down
regulates viral replication. It may be responsible for the regulation of latent state of virus. 7) LTR - (long
terminal repeat) sequences flanking on both sides giving promoter, enhancer and integration signals.

Figure-2 schematic representation of HIV genome

Antigenic variations in HIV

Based on molecular and antigenic differences, two types of HIV have been recognized. The original
isolates of HIV and the related strains present all over the world belong to HIV type 1.The HIV strains,
first isolated from West Africa, which react with HIV type I antiserum very weakly or not at all have been
termed as HIV type 2. It has 40 % genetic similarity and is more closely related to Simian
immunodeficiency virus than to HIV-1.It can cause AIDS but is less pathogenic and is less common. It
infects mainly monkeys and other similar species and is largely confined to West Africa, though
isolations have been reported from some other areas, including Western and Southern India. The
envelop antigens of the two types are different though their core peptides show some cross reactivity.

HIV is a highly mutable virus and exhibits frequent antigenic variations as well as differences in other
features such as nucleotide sequences, cell tropism, growth characteristics and cytopathology. Not only
are there differences between isolates of HIV

90

from different races or persons but also between sequential isolates from the same person, and even
between those obtained from different sites of the same person at the same time. This great variability
is believed to be due to error prone nature of reverse transcription. Antigenic variation is most frequent
in respect of the envelop proteins, but is also seen with other antigens.

HIV-1 strains have been classified in to at least ten subtypes base on sequence analysis of their gag and
env genes. These subtypes have been are designated as A to J and constitute the Group M (For major),
which cause the large majority of HIV-1 infections worldwide. A few HIV-1 strains isolated from West
Africa do not fall within the major group and have been designated as group O ( For Outlier) Some later
isolates of HIV-1 distinct from M and O groups have been called Group N (for new)

Modes of transmission

HIV is transmitted when the virus enters the body, usually by injecting infected cells or semen. There are
several possible ways in which the virus can enter.
1) Sexual contact- In 75 % cases , transmission is by sexual contact. Most commonly, HIV infection is
spread by having sex with an infected partner. The virus can enter the body through the lining of the
vagina, vulva, penis, rectum, or mouth during sex. People who already have a sexually transmitted
disease, such as syphilis, genital herpes, chlamydial infection, gonorrhea, or bacterial vaginitis, are more
likely to acquire HIV infection during sex with an infected partner.

2) Parenteral- In 15 % cases, it is by blood transfusion or blood product transfusion. Blood products are
now tested to minimize this risk. Sharing of unsterilized needles or syringes in drug addicts
contaminated with blood from an infected person can also spread virus. HIV can be spread in health-
care settings through accidental needle sticks or contact with contaminated fluids. HIV can also spread
through organ transplantation. If tissues or organs from an infected person are transplanted, the
recipient may acquire HIV. Donors are now tested for HIV to minimize this risk.

3) From mother to child : Women can transmit HIV to their babies during pregnancy or birth, when
infected maternal cells enter the baby's circulation.30% of children born to infected mothers have the
acquired infection unless virus is treated by antiviral drugs before pregnancy. In nursing mothers
transmission can occur through breast milk.

Mortality/Morbidity

The course of HIV infection is characterized primarily by latency. Unfortunately, profound immune
suppression eventually develops and the illness appears to be almost uniformly lethal. More than
500,000 persons have died of AIDS in the United States. Progression from HIV infection to AIDS occurs 8-
10 years after infection without

91

antiretroviral treatment. In the recent past, most patients would not survive more than 1-2 years
following diagnosis of AIDS. However, since the introduction of highly active antiretroviral therapy
(HAART) and prophylaxis against opportunistic pathogens, death rates from AIDS have declined
significantly. An HIV-positive patient older than 50 years with a nearly undetectable viral load and a CD4
count more than 350 now has less than a 5% chance of dying or progressing to full blown AIDS within 3
years.

Age

Most AIDS cases occur in adults aged 25-49 years (70% of cases). Adolescents and young adults (aged
13-24 y) represent 25% of new cases. Young children represent fewer than 1% of AIDS cases in the
United States. Internationally, children younger than 15 years are estimated to account for close to 10%
of all HIV cases.

Pathogenesis

Infection is transmitted when virus enters the blood or tissues of a person and comes in to contact with
a suitable host cell, principally the CD4 lymphocytes. The virus may infect any cell bearing the CD4
antigen on the surface. Primarily these are the CD4 + helper T lymphocytes. Some other immune cells
possessing CD4 antigens are also susceptible to infection, like B lymphocytes, monocytes and
macrophages including specialized macrophages such as Alveolar macrophages in the lungs and
Langerhans cells in the dermis. Glial cells and microglia cells are also susceptible. Follicular dendritic cells
from tonsils can be infected by HIV without the involvement of CD4. The steps of viral entry in to the
host cell are as follows

1. Attachment of virus into the host cell –Specific binding of the virus to the CD4 receptors is by the
envelop glycoprotein gp120.

2. Cell to cell fusion – For infection to take place the cell fusion is essential. This is brought about by the
transmembrane glycoprotein gp 41. HIV-1 utilizes two major coreceptors along with CD4 to bind to, fuse
with, and enter target cells; these co-receptors are CCR5 and CXCR4, which are also receptors for certain
endogenous chemokines. Strains of HIV that utilize CCR5 as a co-receptor are referred to as macrophage
tropic viruses. Strains of HIV that utilize CXCR4 are referred to as T cell- tropic viruses. Many virus strains
are dual tropic in that they utilize both CCR5 and CXCR4. The infected CD4 cells express a high level of
gp 120 on their surface. The gp 120 on the surface of infected cells leads to fusion of these cells with
CD4 protein of uninfected neighboring cells with formation of multinucleated syncytial cells. The lysis of
fused cells finally occurs resulting in depletion of large number of uninfected cells from the