patho sheet # 5 - Omar Alneaime

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patho sheet # 5 - Omar Alneaime

Post by Shadi Jarrar on 23/2/2011, 12:12 am

بسم الله الرحمن الرحيم

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patho 2.doc
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Portal hypertension:
Increased resistance to portal blood flow may develop from prehepatic,intrahepatic and posthepatic causes.
The dominant intrahepatic cause is cirrhosis, accounting for most cases of portal hypertension.
Portal hypertension in cirrhosis results from increase resistance to portal flow at the level of the sinusoids and compression of central vein by perivenular fibrosis and expanding parenchymal nodules.
Anastomosis between the arterial and portal systems in the fibrous bands also contributes to portal hypertension by imposing arterial pressure on the normally low pressure portal venous system.
The four major clinical consequences are :
1- Ascites
2- Formation of Porto systemic venous shunts
3- Congestive splenumegaly
4- Hepatic encephalopathy (as previously discussed)

Ascites:
Refers to collection of excess fluid in the peritoneal cavity.
It usually becomes detectable when at least 500 ml have accumulated, but many liters may collect and cause massive abdominal distention.
It is generally a serous fluid having ~ 3gm/dl of protein (langely albumin) and the same concentration of solutes as blood.
With longstanding ascots scepage of peritoneal fluid through Tran diaphragmatic lymphatic may produce hydrothoracs more often on the right side. (the side of liver in human body).
The pathogenesis of ascites is complex involving one or more of the following mechanisms: - sinusoidal hypertension: drives fluid into the space of disse which is then removed by hepatic lymphatic's.
-leakage of hepatic lymph into peritoneal cavity with cirrhosis hepatic lymphatic flow exceeds 20L/d exceeding the capacity of the thoracic duct.
-renal retention of sodium and water due to secondary hyperaldosteronisim, despite a total load body sodium greater than normal.(in cases of cirrhosis occurs activation to the renal-angeotenson system and also develop secondary hyperaldosteronisim.

Porto systemic shunts:
With the rise in portal venous pressure, by pass develop wherever the systemic and portal circulation share capillary beds:
-hemorrhoids in the rectum
-esophegogastric varices
-caput medusa (felciform ligaments and abdominal wall collaterals.

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Splenomegaly
Long standing congestion may cause splenomegaly,the degree of enlargement varies widely (usually less than or equal 1000gm) and is not nessecerally correlated with other features of portal hypertension.
Massive splenomagaly may induce hematologic abnormalities attributable to hypersplenism (due to massive congestion of the spleen, blood gathering in spleen so it develops patcytopenia which leads to deficiency in platelets which develops to bleeding disorder due to low platelets.
Jaundice and cholestasis
Jaundice is a common manifestation of liver disease, and results from the retention of bile.
It is yellow discoloration of skin and sclerae and occurs when systemic retention of bilirubin leads to elevated serum level above 2.0 mg/dl.
Cholestastasis is defined as systemic retention of not only bilirubin but also other solutes eliminated in bile (particularly bile salts and cholesterol).
(Cholesterol is disposed outside the body in bile, also bile salts are necessary to digest fat).
Jaundice occurs when the equilibrium between bilirubin production and clearance is disturbed by of of the following mechanisms:
1-exxecive production of bilirubin
2-reduced hepatic uptake
3-impared conjugation
4-decreased hepatocellular excretion
5-impared bile flow (both intrahepatic and extrahepatic obstruction)
The first three mechanisms result in unconjugated hyperbelirubenina
And the last two produce predominantly conjugated hyperbilirubinemia
More than one mechanism may separate to produce jaundice specially in hepatitis which may produce unconjugated and conjugated hyperbilirubinemia
Of the various causes of jaundice the most common are hepatitis, obstruction to bile flow and hemolytic anemia
Question asked by doctor : Hemolytic anemia causes conjugated or unconjugated hyperbilerubenemia? Do u know that liver do conjugate bilirube? To be excreted in bile(because it becomes water soluble) , from where the bilirubin comes from? It comes from the hemoglobin
So it is as follows : hemoglobin TO bileruben TO Liver then the liver conjugates bilerubin
In hepatitis cause both conjugated and unconjugated because the result is
injury to hepatocytes.


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hemolytic anemia causes conjugation because obstruction happens after conjugation so it is conjugation.
Because hepatic machinery for conjugating and exerting bilirubin does not fully mature until about two weeks of age, almost every newborn develops transient and mild uncojugated hyperbilirubinemia, termed neonatal jaundice or physiologic jaundice of the new born..
(بالعامية صفار وبالعراقي ابو صفار)
So physiologic jaundice happens in some newborn because their livers are not mature enough to conjugate bilirubin.
Physiological jaundice disappears with days.

Jaundice may result from inborn errors of metabolism including:

Gilbert syndrome: a relatively common benign inherited condition presenting as mild fluctuating unconjugated hyperbilirubinemia.
The primary cause is decreased hepatic level of glucuronosyltransferase. It affect up to 7% of the population, the hyperbilirubinemia may go undiscovered for years and does not have associated morbidity.

Dubin-Johnson syndrome: result from autosomal recessive defect in the transport protein responsible for hepatocelluar excretion of bilirubin glucuronides across the canalicular membrane. These patient develop conjugated hyperbilirubinemia. Other that having a darkly pigmented liver (from polymerized epinephrine metabolites, not bilirubin ) and hepatomegaly, patients are other wise without functional problem

cholestasis
which results from impaired bile flow due to hepatocellular dysfunction or intrahepatic and extrahepatic biliary obstruction. May also present with jaundice. However, sometimes pruritus (or itching in skin) in the presenting symptoms, presumably related to the elevation in plasma bile acids and their deposition in peripheral tissue especially the skin.
Skin xanthomas (focal accumulation of cholesterol), sometimes appear, the result of hyperlipidemia and impaired excretion of cholesterol.
A chracteristics laboratory finding is elevated serum alkaline phosphatase, an enzyme present in bile duct epithelium and in the canalicular membrane of hepatocytes (happens also in biliary obstruction jaundice).
Alkaline phosphatase also been secreted by Osteoblast in bone marrow.
Those are different isoenzymes, we can differentiate between them by special essays.
Extrahepatic biliary obstruction is frequently amenable to surgical alleviation, thus there is some urgency in making a correct diagnosis of the cause of jaundice and cholestasis.
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Its important to differentiate between hepatic, prehepatic, extrahepatic obstruction of bile duct. And also to know whether it is conjugated or unconjugated hyperbilirubinemia, when we have extrahepatic biliary obstruction, we can surgically remove the stone that obstruct the common bile duct.

Viral Hepatitis
Hepatitis A virus
Known for many years as infection hepatitis. Is a benign, self limited disease with the incubation period of 15 to 50 days (average 28 days).
HAV does not cause chronic hepatitis or a carrier state and only rarely causes fulminant hepatitis.
Case fatalities from HAV occur at a very low rate, about 0.1% and seam to be likely when the patient have preexisting liver disease from other causes such as HBV or alcohol toxicity.
HAV has the largest potential among the hepatitis viruses to cause epidemic and in endemic countries with poor hygiene and sanitation so that natives of such countries have a detectable antibodies to HAV by the age of 10 years. Unlike developed countries no antibodies detected.
Clinical diseases tend to be mild or asymptomatic (in children) and rare after childhood. HAV infection in adult may cause greater morbidity than innocuous childhood infection
HAV is spread by ingestion of contaminated water and foods and is shed in the stool for 2 to 3 weeks before and 1 week after onset of jaundice.
HAV is not shed in any significant amount in saliva, urine, or semen. Fecal-oral contamination during the period of fecal shedding accounts for most cases and explains outbreaks in institutional settings.
Because HAV viremia is transient, blood-borne transmission of HAV occurs only rarely, therefore, donated blood is specifically screened for this virus.(so we don’t check HAV In donated blood, we check only for HBV & HCV)
HAV is a small, non enveloped, single-stranded RNA picornavirus it reaches the liver from the intestinal tract after ingestion, replicates in hepatocytes, and is shed in the bile and feces.
The virus itself does not seen to be toxic in hepatocytes.
Igm antibodies appear in blood at the onset of symptoms detection of anti HAV Igm antibodies is the best diagnostic.
Marker for the disease, IgG antibody persist beyond convalescence and there are no routinely available tests for IgG anti HAV, and therefore the presence of this type of antibody is inferred from the difference between total and Igm anti HAV.
In the u.s the prevalence of seropositivly increases gradually with age, reaching 50% by age 50 years. Prevention and management include:

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1. Hygienic measures focused on disposed of human wastes and personal hygiene.
2. Passive immunization with immune serum globulin for individuals exposed to the virus or those traveling to high-exposure areas.
3. Preexposure prophylaxis using a virus-inactivated vaccine.


Hepatitis B virus (HBV):
HBV can produce
1. Acute hepatitis with recovery and clearance at the virus
2. Non progressive chronic hepatitis
3. Progressive chronic disease ending in cirrhosis
4. fulminant hepatitis with massive liver necrosis
5. Asymptomatic carrier state
HBV-induced chronic liver disease is an important precursor for the development of the hepatocallular carcinoma

HBV remains in blood during the last stages of prolonged incubation period (4-26 weeks) and during active episodes of acute and chronic hepatitis .it is also present in all physiologic and pathologic body fluids with the exception of stools.
HBV is a hardy virus and can withstand extremes of temperature and humidity .thus whereas blood and body fluids are the primary vehicle of transmission, the virus may also spread by contact with body secretions such as semen, saliva, sweat, tears, breast milk, and pathologic effusion.
In endemic region , vertical transmission constitute the main mode of transmission .in areas of low prevalence, horizontal transmission via transfusion ,blood products , dialysis ,needle sticks ,intravenous during abuse and sexual transmission (homo-sexual or hetero-sexual)constitute the primary mechanism of HBV infection.
HBV in adults is mostly cleaved, but vertical transmission produces a high rate of chronic infection.
HBV is a member of the hepadinaviridae a group of DNA containing viruses that cause hepatitis in many animals species
HBV replication does not involve the integration of the virus in the DNA of a host cell but integrated HBV is frequently found in cells.
The genome of HBV is a partially double stranded circular DNA molecule of 3200 nucleotides that encode:
-the precore/core region of a nucleocapsid "core" protein (HBcAg , hepatitis B core antigen )and a pre-core protein designated HBcAg (hepatitis B "e" antigen).HBcAg is retained in infected hapatocyte ; HBcAg is secreted into blood and essential for the establishment of persistent infection.

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-envelope glycoprotein(HBsAg) which maybe produced and secreted into blood in massive amounts .blood HbsAg is immunogenic and can be visualized as spheres or tubule

- a DNA polymerize with reverse transcriptase activity (genomic replication takes place into intermediate RNA known as pregenomic RNA) in this process mutant viral genome are frequently generated .

-HBV-X protein. which acts as a transcriptional transactivator for many viral and host genes .
HBV-X is requires for viral infectivity and may have a rate in the causation of hepatocellular carcinoma by regulating p53 degradation and expression.

After exposure to the virus there is along 45-160 days average (120 day) asymptomatic incubation period which may be followed by acute disease lasting many weeks to months.
The natural course of disease can be followed by serum markers:
-HBsAg appears before the onset of symptoms ,peaks during overt disease ,and then declines to undetectable level in (3-6 months) .
- anti HBs Ab does not rise until the acute disease is over and is usually not detectable for a few weeks to several months after the disappearance of HBsAg anti HBs may persist for life ,conferring protection this is the basis for current vaccination using noninfectious HbsAg.


Good luck



Sorry for being late 


7/2/2011
Done by
Omar Alneaime







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Shadi Jarrar
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عدد المساهمات : 997
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تاريخ التسجيل : 2009-08-28
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الموقع : Amman-Jordan

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