Liver

2. ActualityActuality
 The diseases of liver and bile excretory system take considerable
specific weight in a general morbidity of the population, and last
decade the further growth of them was increased.
 Technological revolution and associated with it the negative
ecological shifts have resulted in useful increase of frequency and
spread spectrum of diseases of liver and cholic tracts. In
connection with urbanisation of life, hypokinesia, and also such
negative phenomenon as alcoholism, morbidity the hepatitis and
cirrhosis of liver, cholelithiasis and cholecystitis considerably has
increased.
 The chemicalization of effecting, agriculture, mode of life activities
and medicine promoted growth of frequency of toxic and
medicamental damages of liver. Sharp increase of medical
manipulations, blood transfusion have stimulated useful increase
of morbidity by serumal hepatitis.
 The main morphological types of damages of liver is hepatitis,
cirrhosis, cancer. Etiological value in formation of the majority of
acute and chronic diseases of liver have the agents many zymotic
and infection diseases (viruses, bacteria, spirochetes, pathogenic
fungi, elementary, helminths) and toxic substances - hepatotoxins,
including alcohol and medicine drugs.
 Therefore preventive maintenance encompasses them the broad
audience of problems. The pathogenetic treatment of diseases of
liver bases on knowledge of their mechanisms of disturbance of
structure and function of liver, which one are revealed with the help
biochemical, cytochemical, radioisotope and other method of
testings.

3. CONTENTCONTENT
1.1. Microscopic architecture of the liver parenchyma.Microscopic architecture of the liver parenchyma.
2.2. The liver is a big chemical laboratory.The liver is a big chemical laboratory.
Carbohydrate, Protein, and Lipid Metabolism.Carbohydrate, Protein, and Lipid Metabolism.
 The cases of liver pathology.The cases of liver pathology.
 Carbohydrate metabolism disorder in liver.Carbohydrate metabolism disorder in liver.
 Fat metabolism disorder. Liver fatty infiltration.Fat metabolism disorder. Liver fatty infiltration.
 Protein metabolism infringement.Protein metabolism infringement.
1.1. Microelements metabolism disorder in liver.Microelements metabolism disorder in liver.
2.2. Methods of experimental design of violations of function of liver.Methods of experimental design of violations of function of liver.
3.3. Functional insufficiency of liver, its etiology, pathogenesis, basic displays.Functional insufficiency of liver, its etiology, pathogenesis, basic displays.
4.4. A metabolic disturbance is at the diseases of liver.A metabolic disturbance is at the diseases of liver. Antitoxic liver function disorder.Antitoxic liver function disorder.
5.5. An exchange of bilirubin in an organism in a norm.An exchange of bilirubin in an organism in a norm.
6.6. Jaundices: classification, etiology, pathogenesis, basic clinical displays of separateJaundices: classification, etiology, pathogenesis, basic clinical displays of separate
kinds.kinds.
7.7. Enzymopathic jaundices (Gilbert's syndrome, CriglerEnzymopathic jaundices (Gilbert's syndrome, Crigler -- Nagar syndrome, Dubin-Nagar syndrome, Dubin-
Johnson syndrome).Johnson syndrome).
8.8. Differential diagnostics of separate types of jaundices is on the basis ofDifferential diagnostics of separate types of jaundices is on the basis of
information of laboratory researches of physiology liquids of organism.information of laboratory researches of physiology liquids of organism.
9.9. Hepatocerebral comaHepatocerebral coma: pathogenesis of basic displays, medical measures: pathogenesis of basic displays, medical measures
10.10. Cirrhosis of the liver.Cirrhosis of the liver.
11.11. Disorders of the gallbladder and extrahepatic bile ducts.Disorders of the gallbladder and extrahepatic bile ducts.

4. LiverLiver
• Largest internal organ
• Weighs about 1400-1800 gram
• Located on right side under
ribcage
• Ability to regenerate
• Has over 500 vital functions
• Involved in many digestive,
vascular and metabolic
activities

6. NN
OO
FIBROUSFIBROUS
TISSUETISSUE

7. Blood Supply of the Liver
Hepatic Arterial Autoregularity
Vasodilatation
Hepatic Arterial Autoregularity
Vasodilatation

8. The following processes takeThe following processes take
place in the liver:place in the liver:
1.1. The creation of bileThe creation of bile pigments synthesispigments synthesis of cholesterol,of cholesterol, synthesissynthesis
and secretion of bileand secretion of bile..
2.2. TheThe detoxicationdetoxication of toxic products, coming from gastrointestinalof toxic products, coming from gastrointestinal
tract.tract.
3.3. TheThe synthesis of proteinssynthesis of proteins (proteins of plasma of blood among(proteins of plasma of blood among
them), their deposition, transamination and desamination ofthem), their deposition, transamination and desamination of
aminoacids, the formation of urea, the synthesis of creatinine.aminoacids, the formation of urea, the synthesis of creatinine.
4.4. TheThe synthesis of glycogenesynthesis of glycogene from monosaccharides.from monosaccharides.
5.5. TheThe oxidation of fatty acidsoxidation of fatty acids, the formation of acetone (ketone, the formation of acetone (ketone
bodies).bodies).
6.6. TheThe deposition and exchangedeposition and exchange ofof vitaminsvitamins ((АА,, ВВ, D), the deposition, D), the deposition
ofof iron, copper, zinc ionsiron, copper, zinc ions..
7.7. TheThe regulationregulation of the balance betweenof the balance between coagulantcoagulant andand
anticoagulant blood systemanticoagulant blood system, the formation of heparine., the formation of heparine.
8.8. TheThe destructiondestruction of someof some microorganisms, bacterialmicroorganisms, bacterial and otherand other
toxinstoxins..
9.9. TheThe deposition of plasma of blooddeposition of plasma of blood, the regulation of a total amount, the regulation of a total amount
of blood.of blood.
110.0. HemopoiesisHemopoiesis in the fetus.in the fetus.

9. Functions of the LiverFunctions of the Liver
Type Function
Metabolic
Absorptive Period Converts glucose to glycogen and triglycerides; stores glycogen.
Converts amino acids to fatty acids or stores amino acids. Makes
lipoprotein from triglycerides and cholesterol.
Postabsorptive
Period
Produces glucose from glycogen (glycogenolysis) and fatty acids and
amino acids (glyconogenesis). Converts fats to ketones (accelerated
if fasting). Produces urea from protein catabolism.
Immunologic
Metabolic
Transformation
Macrophages filter blood.
Detoxifies or conjugates waste products, hormones, drugs.
Clotting Functions Produces several essential clotting factors.
Plasma Proteins Synthesizes albumin and other plasma proteins.
Exocrine
Functions
Synthesizes bile salts.
Endocrine
Functions
Involved in activation of vitamin D. Produces angiotensinogen. Secretes
insulin-like growth factors (somatomedin).

10. Liver Damage
Inflammation – immune
response
Fibrosis – development of
scar tissue
Cirrhosis – a process
where liver cells are
destroyed and replaced with
scar tissue
Hepatocellular Carcinoma
– type of liver cancer

11. DisordersDisorders
Liver FunctionLiver Function
Hepatic TestHepatic Test
JaundiceJaundice
Biliary Tract DiseaseBiliary Tract Disease
– Cholelithiasis-CholedocholithiasisCholelithiasis-Choledocholithiasis
– Cholecystitis-CholangitisCholecystitis-Cholangitis
– Biliary tract obstructionBiliary tract obstruction
Hepatic DiseaseHepatic Disease
– Hepatitis Acute & ChronicHepatitis Acute & Chronic A/B/C/D/E, ETOH/drugA/B/C/D/E, ETOH/drug
– CirrhosisCirrhosis
– Hepatic FailureHepatic Failure
Neoplasm (later section)Neoplasm (later section)

12. ETHIOLOGYETHIOLOGYETHIOLOGYETHIOLOGY
Infectious agentsInfectious agents – hepatitis virus, Koch’s bacillus, pale– hepatitis virus, Koch’s bacillus, pale
Spirochaeta, Actynomyces, Echinococcuses,Spirochaeta, Actynomyces, Echinococcuses,
Ascarides;Ascarides;
1.1. Hepatotropic poisons, including medicinesHepatotropic poisons, including medicines ––
tetracycline, PASA (paraaminosalycil acid),tetracycline, PASA (paraaminosalycil acid),
sulphanilamides, industrial poisons (CClsulphanilamides, industrial poisons (CCl44, arsenic,, arsenic,
chloroform); plants poisons (aphlatoxine,chloroform); plants poisons (aphlatoxine,
muscarine);muscarine);
2.2. Physical influencesPhysical influences – ionizing radiation;– ionizing radiation;
3.3. Biological substancesBiological substances – vaccines, serums;– vaccines, serums;
4.4. Blood flow violationsBlood flow violations – thrombosis, embolism,– thrombosis, embolism,
venous hyperemia;venous hyperemia;
5.5. Endocrine pathologyEndocrine pathology – diabetes mellitus,– diabetes mellitus,
hyperthyroidism;hyperthyroidism;
6.6. TumorsTumors;;
7.7. Hereditary enzymes pathologyHereditary enzymes pathology..

13. PATHOPHYSIOLOGY OF LIVER
• Ethiology of liver
functions violation
• In the prevailing majority of
cases, liver pathology is
presented by two processes:
1) Hepatitis – liver
inflammation;
2) Cirrhosis – the
intensified diffuse growth of
the new connective liver
tissue (stroma) on the
background of dystrophic
and necrotic hepatocytes
(parenchyma) damage.

14. Liver diseases pathogenesis is
characterized by two main mechanisms:
- the direct hepatocytes affection:the direct hepatocytes affection:
a)a) dystrophy,dystrophy,
b)b) necrosis;necrosis;
-- autoimmune injury of hepatocytes byof hepatocytes by autoantibodies,,
which are formed in response to hepatocyteswhich are formed in response to hepatocytes
antigens structure changed.antigens structure changed.
 Liver affection by any of the above described etiologicLiver affection by any of the above described etiologic
factors may lead to such state, when the liverfactors may lead to such state, when the liver
becomes not capable to execute its functions and tobecomes not capable to execute its functions and to
provide the homeostasis. That state is called theprovide the homeostasis. That state is called the liver
insufficiency..
 It may beIt may be total, when all functions are suppressed;, when all functions are suppressed;
 oror partial, when only some functions suffer, e.g., the, when only some functions suffer, e.g., the
bile-forming one.bile-forming one.

16. Metabolic function failureMetabolic function failure
 Liver is the central organ of the chemical homeostasis.Liver is the central organ of the chemical homeostasis.
It is placed between theIt is placed between the collar veincollar vein from one side,from one side,
and theand the systemic circulationsystemic circulation from the other. Itsfrom the other. Its
placement should be recognized as the optimal oneplacement should be recognized as the optimal one
for the execution of the metabolic function.for the execution of the metabolic function.
 All substances coming with food, excluding only those,All substances coming with food, excluding only those,
which are transported via mesentery lymphaticwhich are transported via mesentery lymphatic
vessels into the breast blood stream, must go throughvessels into the breast blood stream, must go through
the liver. Only in such way, with liver participation,the liver. Only in such way, with liver participation,
food is either decomposed, or expelled, or deposited.food is either decomposed, or expelled, or deposited.
 TheThe metabolic liver functionmetabolic liver function means livermeans liver
participation in the chemical elements metabolism ofparticipation in the chemical elements metabolism of
almost all classes – carbons, fats, proteins, enzymes,almost all classes – carbons, fats, proteins, enzymes,
vitamins.vitamins. HepatocytesHepatocytes affection negativelyaffection negatively
influences each of those metabolisms.influences each of those metabolisms.

17. Carbohydrate metabolism disorderCarbohydrate metabolism disorder
 GlycogenGlycogen synthesis and its splitting are the main regulatorysynthesis and its splitting are the main regulatory
processes, with the help of which liver keeps glucoseprocesses, with the help of which liver keeps glucose
homeostasis, particularly its level in blood. The slowing-downhomeostasis, particularly its level in blood. The slowing-down
of glycogen synthesis may happen at any hepatocytesof glycogen synthesis may happen at any hepatocytes
affection. That leads to the simultaneous limitation ofaffection. That leads to the simultaneous limitation of
glucuronic acid formation, which is indispensable inglucuronic acid formation, which is indispensable in
disintoxication of many exogenic poisons (industrial toxins)disintoxication of many exogenic poisons (industrial toxins)
and final metabolites (cadaverine, putrescine) andand final metabolites (cadaverine, putrescine) and
unconjugated bilirubin.unconjugated bilirubin.
 TheThe slowing-down of glycogen splittingslowing-down of glycogen splitting in liver is conditionedin liver is conditioned
by corresponding enzymes defect or their total absence.by corresponding enzymes defect or their total absence.
The diseases belonging to that group are calledThe diseases belonging to that group are called
glycogenosises, all being of inheritable origin. They areglycogenosises, all being of inheritable origin. They are
manifested by glycogen accumulation in liver, bymanifested by glycogen accumulation in liver, by
hepatomegaly and hypoglycemia. Several forms arehepatomegaly and hypoglycemia. Several forms are
distinguished among them, depending which enzymes is notdistinguished among them, depending which enzymes is not
synthesized.synthesized.

18. 1.1. The slowing-down of glycogenThe slowing-down of glycogen synthesissynthesis ((limitation oflimitation of
glucuronic acid formationglucuronic acid formation,, which leads to accumulation of manywhich leads to accumulation of many
exogenic poisons (industrial toxins) and final metabolitesexogenic poisons (industrial toxins) and final metabolites
(cadaverine, putrescine) and unconjugated bilirubin.(cadaverine, putrescine) and unconjugated bilirubin.
2.2. Slowing-down of glycogenSlowing-down of glycogen dissociation (dissociation (glycogenosisglycogenosis ––
hereditary diseaseshereditary diseases,, which is due towhich is due to enzymesenzymes abnormality andabnormality and
lead to deposit oflead to deposit of glycogenglycogen and carbohydrate liver dystrophyand carbohydrate liver dystrophy
ExamplesExamples::
Glycogenosis I typeGlycogenosis I type ((HirkeHirke’s’s diseasedisease) –) – defect of glucose-6-defect of glucose-6-
phosphatasephosphatase
Glycogenosis III typeGlycogenosis III type ((KorrKorry’sy’s disease, Forbsdisease, Forbs’s’s diseasedisease) –) – deficitdeficit
of amilo-1,6-glucosidaseof amilo-1,6-glucosidase
Glycogenosis VI type (Glycogenosis VI type (Gers’s diseaseGers’s disease)) –– deficit of liverdeficit of liver
phosphorilase complex – proteinkinase, phosphorilase kinasephosphorilase complex – proteinkinase, phosphorilase kinase
and phosphorilaseand phosphorilase
Manifestations:Manifestations: hepatomegalia and hypoglycemiahepatomegalia and hypoglycemia
Carbohydrate metabolism disorderCarbohydrate metabolism disorder

19. Glycogenosis of type I
• Type 1= Von Gierke’s:
– Shortly after birth: Severe
lifethreatening Hypoglycemia
– Lactic acidosis –due to isolated
glycolysis of glucose-6-phosphateglucose-6-phosphate
(G-6-Ph).
– Hyper-uricemia, hyper lipidemiaHyper-uricemia, hyper lipidemia
– Increased association with epistaxis
– *HepatomegalyHepatomegaly
– **Adverse response to Glucagon with
worsening Lactic acidosis
• Management requires IV glucose, and
then as outpt, close NG corn-starch or
glucose solution administration to achieve
close to nl glucose homeostasis.
• Frequent snacks and meals. Continuous
nighttime glucose infusions up to the age
of 2.

20. Glycogenosis of type IIIGlycogenosis of type III Glycogenosis of type IIIGlycogenosis of type III
((Korri disease, ForbsKorri disease, Forbs
diseasedisease, so called debrancher, so called debrancher
enzyme defect) is the deficit ofenzyme defect) is the deficit of
amilo-1,6-glucosidase, theamilo-1,6-glucosidase, the
enzymes, which breaks theenzymes, which breaks the
connections in the places ofconnections in the places of
glycogen molecule branching.glycogen molecule branching.
That is why the branchedThat is why the branched
molecule does not turn into amolecule does not turn into a
direct chain of glucosedirect chain of glucose
monomers.monomers.
 In response to the decrease ofIn response to the decrease of
glucose level in blood,glucose level in blood,
glycogen is rended only to theglycogen is rended only to the
branching areas. In the result ofbranching areas. In the result of
that, a lot of unsplittedthat, a lot of unsplitted
glycogen accumulates inglycogen accumulates in
hepatocyteshepatocytes.. Hepatomegalia,Hepatomegalia,
hypoglycemiahypoglycemia andand crampscramps
take place. However, some parttake place. However, some part
of glucose does come intoof glucose does come into
blood.blood.
Glycogen in the Liver (left stained
to show glycogen, right normal)
Glycogen in Muscle Cells

21. Type VІ glycogenosis – Hers’ diseaseType VІ glycogenosis – Hers’ disease
 Illness arises as result of insufficiency ofIllness arises as result of insufficiency of
hepatic phosphorilase complex. Glycogenhepatic phosphorilase complex. Glycogen
accumulates in liver. Typical sign isaccumulates in liver. Typical sign is
hepatomegalia.hepatomegalia.

22. Fat metabolism disorder. Liver fatty infiltration
• One of the most striking liver functions is the critical evaluation of the
correlation among food substances, which come to it from the stomach
via the collar vein. If there is no balance in food ingredients, the liver
reacts very peculiarly – it takes for a temporal depositing the surplus
substances and stores them until the necessary product appears to
construct macromolecules and to expel them into blood. At pathologic
conditions, liver stores mainly fats. That phenomenon is called the fats
liver infiltration.
• Exogenic triglycerides are hydrolyzed in the intestines, and in
enterocytes they are resynthesized and come into the liver as a part of
hylomicrones. They come into hepatocytes and are decomposed to fatty
acids and glycerin. Fatty acids are partly oxidized and partly participate
in the formation of triglycerides, phospholipids and cholesterin ethers.
The formed triglycerides are expelled by the liver into blood in the form
of lipoproteides of very low and of low density.
• The production of lipoproteides by the liver demands the close linkage
of the processes of lipidic and albumin synthesizes. The availability of
the starting products is also indispensable, but in the balance amount.
The reason of fats infiltration can be any agent, which violates this
balance in such way, that lipids amount become higher in the correlation
to albumins amount. In the result of that it is impossible to involve the
liver lipids into the synthesis of lipoproteides and to excreta them into
blood. A part of lipids deposits in liver.

23. FATTY
LIVER
Obesity
Diabetes
Toxic

24. Liver fats infiltration becomes possible in
such cases:
a) The increased lipolysis in the fat tissue, most often – at the
decompensated diabetes mellitus. The lipidic predecessors
of lipoproteides (fatty acids) are so high at diabetes patients,
that they have no time to start to participate in triglycerides
synthesis and the last – in lipoproteides synthesis.
b) Hypoglycemia (at starvation or glycogenosis) can provoke
the liver fats infiltration. In the conditions of glucose deficit,
the insulin production secondarily decreases and lipolysis is
activated. The excess of free fat acids, which come into the
liver, can exceed the abilities to join triglycerides into
lipoproteides. The incompatibility between the delivery and
synthesis processes provokes the fats infiltration.
c) Lipoproteides production and fats expelling from the liver
decrease in the conditions, when sources of aminoacids are
restricted (e.g., at albumin starvation), thus apoproteines
synthesis is decreased. Lipides, as raw material for
lipoproteides synthesis, remain unused because the deficit of
protein component.

25. Liver fats infiltration becomes possible in
such cases:
d) The fatty infiltration can be caused by the lipotropic
aminoacids deficit (choline and metionine) in food.
e) The same picture can be caused by B12 –
hypovitaminosis and folic acid deficit, because it is
caused by endogenic choline deficit.
f) The fatty infiltration can be also conditioned by toxins
influences, for example amanitotoxine, which blockes ß-
oxidixation of fatty acids in mitochondrias.
g) Hypoxia is believed to be one of the important
pathogenic links of fatty infiltration.
All factors, which cause the lasting hypoxia or suppress
mitochondrias, the limit of hepatocytes energy
synthezise, lead to the fatty distrophy of the liver.

27. Protein metabolism infringementProtein metabolism infringement
• The main consequences of albumin metabolism infringement
at the liver affection are as follows:
a) Hypoproteinemia is the result of blood level decrease of
albumins, α- and β-globulins, which are synthesized by
hepatocytes. It leads to hypooncia and as the result edema
develops.
b) Hyper-gamma-globulinemiais the result of gamma-
globulines synthesize increase by Kuffer’s cells and
plasmocytes.
c) Dysproteinemia is the result of macroglobulins and
crioglobulins accumulation.
d) Hemorrhagic syndrome in the result of the decreased
synthesis of blood coagulation factors (besides VIII factor).
e) The increase of blood RN (retarded nitrogen) in the result of
the decreased urea synthesis and ammonia accumulation.
That happens at 80% parenchyma affection.
f) Increase of enzymes level in blood (aminotranspherases).

28. Microelements metabolism disorder
• The well-known example is Wilson’s
disease, when copper deposits in
hepatocytes. Normally, the copper, which
comes into a hepatocyte, is distributed
among the cytoplasm and the subcellular
organels.
• There is a special albumin in the liver –
metall-thionein, which binds copper. It
functions as a temporal copper depositor. In
some time, the deposited copper enters the
metal-containing enzymes, or is withdrawn
with bile.
• Some persons have got metall-thionein with
very high relation to copper, which is
determined hereditary. That shifts of copper
liver pool balance in such a way that leads to
the drop of its secretion with bile and to the
decrease of its joining the ceruloplasmin, an
albumin that transports copper in blood.
• At the long-term copper accumulation by
abnormal metall-thionein, the binding centres
satiate, and copper excess is absorbed by
liver lysosomes. The metal is accumulated in
hepatocytes and leads to hepatomegalia.

30. Wilson’s DiseaseWilson’s Disease
• Pathogenesis:Pathogenesis:
– a rare treatable genetica rare treatable genetic disorder of copperdisorder of copper
metabolism.metabolism.
– There is an abnormal accumulation of copper inThere is an abnormal accumulation of copper in
the hepatocytes.the hepatocytes.
– This is a metabolic disorder affecting basalThis is a metabolic disorder affecting basal
ganglia, eyes, & kidney.ganglia, eyes, & kidney.
– An autosomal recessive defect (ATP7B gene) inAn autosomal recessive defect (ATP7B gene) in
ATP-mediated hepatocyte copper transport.ATP-mediated hepatocyte copper transport.
– Results in lack of Cu incorporation intoResults in lack of Cu incorporation into
ceruloplasminceruloplasmin..
– The serum ceruloplasm & copper are both lowThe serum ceruloplasm & copper are both low
(copper low because it can’t be carried)(copper low because it can’t be carried)

32. Antitoxic function disorder
• The antitoxic liver function aggravation is connected to the
violation of certain reactions directed to rendering harmless
the toxic substances, which are formed in an organism or
come from outside:
a) Urea synthesis disorder resulting in ammonia
accumulations.
b) Conjugation disorder, i.e. the formation of pair compounds
with glucuronic acid, glycin, cystine, taurine. In such way
unconjugated bilirubin, scatol, indol, phenol, kadaverin,
thyramin, etc. become harmless.
c) Acetylization disorder leading to
sulphamides accumulation at their long-
term usage.
d) Oxidization disorder leading to the
accumulation of aromatic carbons.
Deep disorders of the antitoxic liver
function bring forward liver
encephalopathy and liver comaencephalopathy and liver coma.

35. • The Hepatocerebral coma is a syndrome developing in the result of the
liver insufficiency. It is characterized by the deep affection of the central
nervous system (consciousness loss, reflexes loss, cramps, bleeding and
breathing disorders).
• The most frequent liver coma reasons are as follows:
viral hepatitis, toxic liver dystrophy, cirrhosis, portal hypertensia.
• The main mechanism of the central nervous system damage is the
accumulation of toxic neurotropic substances:
• a) Ammonia. In liver mytochondria urea is synthesized from ammonia.
• At liver affection, ammonia does not join the urea cycle (ornitative cycle).
Ammonia binds with α-ketoglutaric acid and forms glutaminic acid.
• Exclusion of α-ketoglutaric acid from Krebs cycle slows down ATP and
decreases energy outcome in neurons, decreases their repolarization and
function.
• b) Rotting products, which are absorbed from the large intestine – phenol,
indol, skatol, kadaverine, thyramine.
• c) Low-molecular fatty acids – oleic, capronic, valeric. They interact with
lipids of neurons membranes and slow down the excitement transfer.
• d) Pyroracemic acid derivatives – acetoine, butylenglicol.

36. Other pathogenic links:
a) Aminoacid disbalance in blood –
- the decrease of valine, leucine, isoleucine;
- the increase of phenylalanine, thyrosine, thryptophane,
metionine.
In the result of that, false mediators are synthesized –
oktopamine, β-phenilethyramine, which displace
noradrenaline and dophamine from synaptosomes and
block synaptic transfer to the central nervous system.
b) Hypoglycemia resulting from gluconeogenesis or
glycogenolysis weakening in hepatocytes that
additionally restricts ATP synthesis in the brain.
c) Hypoxia of haemic type in connection with the
blockage of the breathing surface of erythrocytes by
toxic substances.
d) Hypopotassiumia as the result of the secondary
aldosteronism.
e) Disorder of the acid-basic balance in neurones and
in intercellular liquid.

37. • Bile is made by all hepatocytes and
consists of water, bile salts, bilirubin,
cholesterol, fatty acids, lecithin, and
electrolytes. Except for water, the most
abundant substance in bile is bile salt.
• Bile salts are synthesized in the liver
from cholesterol that either has been
delivered to the liver from the small
intestine or synthesized directly by the
liver in the process of fat metabolism.
• All hepatic cells participate in making
bile and each secretes bile into the
small bile canaliculi that surround all
liver cells.
• The canaliculi empty into progressively
larger ducts that ultimately join into the
hepatic duct and common bile duct.
These ducts deliver bile either to the
gallbladder for storage or into the
intestine directly.
• Bile salts function in the digestion of
fat and are normally recycled after use
in the small intestine.
• Without bile, as much as 40% of fats in
the diet would not be absorbed across
the intestine and so would be lost in
the stool. The absorption of fat-soluble
vitamins across the small intestine
would be similarly affected.

39. Disorders of bile formation and secretion
• Liver cells secret bile. It consists of water, bile acids, bile pigments, cholesterine,
phospholipids, fat acids, mucin and other ingredients.
• The main indicator of bile formation and bile secretion is the secretion of bile
pigments, i.e. bilirubin and its derivatives. Bilirubin is formed in SMP cells (liver,
spleen, red bone marrow) from the gem by chipping-off iron by means of
hemoxygenase (biliverdin) and further renovation by biliverdin-reductase
(unconjugated bilirubin). Its paradoxical, but the transformation of biliverdin into
bilirubin decreases the substance solutability, and its secretion becomes problematic.
• Unmconjugated bilirubin is not soluble in water. In blood, 75 % of it binds with
albumin and circulates in such form. Unconjugated bilirubin approaches the
hepatocyte and binds with lipandin, the albumin placed on its surface, or with γ-
albumin, which might be identical to glutation-5-transpherase. Ligandin transports
unconjugated bilirubin to microsomes, where it binds with glucuronic acid
(conjugation). The reaction is catalized by microsomic UDP-glucuroniltranspherase
(uridine-dyphosphate- glucuroniltranspherase).
• Monoglucuronide and bilirubin dyglucuronide are formed. The conjugated
bilirubin is secreted into the duodenum and is removed from the organism as
stercobilin with feces and urine. A part of the conjugated bilirubin is restored up to
urobilinogen in liver ducts, gallbladder and small intestines under the influence of
microflore enzymes.
• Urobilinogen does not enter the general blood flow and normally is not excreted. It
is absorbed into the liver vein and is splitted by the liver to pirolites.
• The violation of bile formation and bile excretion is manifested by
characteristic syndromes: jaundice, cholemia and steatorrhea.

41. Disorders of bile formation
and bile excretion
Disorders of bile formation
and bile excretion
 Clinical syndromes
1. Jaundice (icterus) - means yellowish of skin, mucous
membranes and sclera in the result of bile
pigments deposit;
2. Cholemia - appears at obstructive and
parenchimatous jaundices, when bile comes into
the blood. It is caused by bile acids and the main
symptoms are bradycardia, arterial hypotension,
excitability, skin itch;
3. Steatorea - syndrome, which occurs due to violation
of digestion and fats absorption. Fats are excreted
with faeces. The fat-like vitamins А, D, Е, K are
being lost together with fat
 Clinical syndromes
1. Jaundice (icterus) - means yellowish of skin, mucous
membranes and sclera in the result of bile
pigments deposit;
2. Cholemia - appears at obstructive and
parenchimatous jaundices, when bile comes into
the blood. It is caused by bile acids and the main
symptoms are bradycardia, arterial hypotension,
excitability, skin itch;
3. Steatorea - syndrome, which occurs due to violation
of digestion and fats absorption. Fats are excreted
with faeces. The fat-like vitamins А, D, Е, K are
being lost together with fat

42. JaundiceJaundice
 Jaundice is the yellowish discoloration of Jaundice is the yellowish discoloration of
the skin and sclera of the eyes seen as a the skin and sclera of the eyes seen as a
result of excess bilirubin in the blood result of excess bilirubin in the blood
(greater than 1.2 mg/dL(greater than 1.2 mg/dL or <20,5 mcM/L or <20,5 mcM/L). ).
 Jaundice (icterus) is detectable clinically Jaundice (icterus) is detectable clinically
when the serum bilirubin is greater than 50 when the serum bilirubin is greater than 50
μμmol/L (3 mg/dL). mol/L (3 mg/dL).
 Bilirubin is a product of red blood cell Bilirubin is a product of red blood cell
breakdown. Jaundice is also referred to as breakdown. Jaundice is also referred to as
icterus. icterus.
 There are three main types of jaundice: There are three main types of jaundice:
1) 1) hemolytic jaundice, hemolytic jaundice,
2) 2) intrahepatic jaundice, intrahepatic jaundice,
3) 3) extrahepatic obstructive jaundice.extrahepatic obstructive jaundice.

46. Jaundice (icterus)
• This means yellowishing of skin, mucous membranes and sclera in
the result of bile pigments depositing in them. There are three types
of jaundice:
A. Hemolytic jaundice, conditioned by the surplus formation of
unconjugated bilirubin or by the violation of its transportation.
B. Parenchimatous jaundice, conditioned by hepatocytes pathology.
C. Obstructive jaundice, which takes place on the basis of the
insufficient bile outflow.
• The normal plasma concentration of bilirubin is maximally 17 μmol/L
(1,2 mg/dL). If it rises to more than 30 μmol/L, the sclera become yellow; if
the concentration rises further, the skin turns yellow as well (jaundice
[icterus]). Several forms can be distinguished:

47. • Appears, as a rule, in the result
of the excess erythrocytes
haemolysis. Its reasons are
the same as for the haemolytic
anaemia.
• The special features of bile
pigments exchange at this
jaundice are as follows:
1) in the blood – high level of
unconjugated bilirubin;
2) in the feaces – stercobilin
concentration is increased;
3) in the urine – stercobilin
concentration is increased too,
4) no cholemia.

49. Inheritable hepaticInheritable hepatic
jaundicejaundice
 The basis ofThe basis of inheritable hepatic jaundiceinheritable hepatic jaundice is theis the
violations of theviolations of the unconjugated bilirubinunconjugated bilirubin capture bycapture by
hepatocytes, its insufficient conjugation or itshepatocytes, its insufficient conjugation or its
insufficientinsufficient isolation of the conjugated bilirubin fromisolation of the conjugated bilirubin from
the hepatocytethe hepatocyte..
 The insufficient capture of the unconjugated bilirubinThe insufficient capture of the unconjugated bilirubin
brings forwardbrings forward Jilbert’s syndromeJilbert’s syndrome. The genetic. The genetic
defect means the blockage of ligandin (defect means the blockage of ligandin (γ-albuminγ-albumin))
synthesis, whichsynthesis, which transports unconjugated bilirubintransports unconjugated bilirubin
through the membrane to thethrough the membrane to the inside of theinside of the

50. Differential Diagnosis of Hereditary Jaundice with Normal Liver Differential Diagnosis of Hereditary Jaundice with Normal Liver
Chemistries & No Signs or Symptoms of Liver DiseaseChemistries & No Signs or Symptoms of Liver Disease
Unconjugated HyperbilirubinemiaUnconjugated Hyperbilirubinemia
Crigler-Najjar Syndrome
Gilbert’s Type I Type II
Incidence
Inheritance mode
Serum bilirubin
usual total (mg/dL)
Defect
Age at onset of
jaundice
<7% of pop’n Very rare Uncommon
AD AR AD
<3; <6 >20 <20
Mostly B1; inc. All indirect All indirect
with fasting
Hepatic UDP-glucuronyl transferase activity
Decreased Absent Marked dec.
Adolescence Infancy Childhood,
adolescence

51. Differential Diagnosis of Hereditary Jaundice with Differential Diagnosis of Hereditary Jaundice with
Normal Liver Chemistries & No Signs or Symptoms of Normal Liver Chemistries & No Signs or Symptoms of
Liver DiseaseLiver Disease
Unconjugated HyperbilirubinemiaUnconjugated Hyperbilirubinemia
Crigler-Najjar Syndrome
Gilbert’s Type I Type II
Usual clinical
features
Liver biopsy
Treatment
Appear in early Jaundice, Asymptomatic
adulthood; kernicterus in jaundice,
often 1st
re- infants, kernicterus
cognized w/ young adults rare
fasting
Normal Normal Normal
Not needed Liver transplant Phenobarbital

52. InheritableInheritable
hepatichepatic
jaundicejaundiceThe low intensity of conjugationThe low intensity of conjugation
depends on the defecit of UDP-depends on the defecit of UDP-
glucuroniltranspherasa ofglucuroniltranspherasa of
hepatocytes.hepatocytes. Krigler-NayarKrigler-Nayar
syndromesyndrome takes place.takes place.
At theAt the total absence of the enzymestotal absence of the enzymes ((type Itype I)), the classic, the classic
bilirubinousbilirubinous encephalopathy developsencephalopathy develops; at autopsy the nucleus; at autopsy the nucleus
jaundice is found out. Thejaundice is found out. The majority of sick children diemajority of sick children die, and, and
those, who don’t,those, who don’t, suffer with choreoathetosissuffer with choreoathetosis..
Child’s brainChild’s brain is especially disposed to the development ofis especially disposed to the development of
bilirubinous encephalopathybilirubinous encephalopathy within the first weeks orwithin the first weeks or
months of life.months of life.
AtAt type IItype II thethe conjugative ability of hepatocytesconjugative ability of hepatocytes
increasesincreases afterafter phenobarbitalphenobarbital introduction. Theintroduction. The
introduction this substance within 2-3 weeksintroduction this substance within 2-3 weeks
normalizes bilirubin level in blood.normalizes bilirubin level in blood.

53. Differential Diagnosis of Hereditary Jaundice with NormalDifferential Diagnosis of Hereditary Jaundice with Normal
Liver Chemistries & No Signs or Symptoms of Liver DiseaseLiver Chemistries & No Signs or Symptoms of Liver Disease
Conjugated HyperbilirubinemiaConjugated Hyperbilirubinemia
Dubin-Johnson Rotor’s Syndrome
Incidence
Inheritance mode
Serum bilirubin usual
total (mg/dL)
Defect
Urine total coproporphyrin
Age at onset of jaundice
Usual clinical features
Oral cholecystogram
Liver biopsy
Treatment
Uncommon
AR
2-7; < 25
Direct ~ 60%
Impaired biliary
excretion
Normal
Childhood,
adolescence
Asymptomatic
jaundice in young
adults
GB not visualized
Charac. Pigment
(black liver →
metabolites of
catecholamines)
Not needed
Rare
AR
2-7; < 20
Direct ~ 60%
Impaired biliary
excretion
Increased
Adolescence, early
adulthood
Asymptomatic
jaundice
Normal
No pigment
None

55. Inheritable
hepatic jaundice
 The laboured discard of the conjugated
bilirubin from the hepatocyte into the bile is
clinically displayed by two syndromes:
 The acquired liver jaundice is connected with the
hepatocytes affection by virus, toxic and other
agents.
 Its pathogenic mechanism is the decrease of
conjugation processes.
Dubin-JohnsonDubin-Johnson RotorRotor

56. Parenchymatous jaundice is
conditioned by endogenic
(inheritable) and outside
influences.
Parenchymatous jaundiceParenchymatous jaundice is
characterized by the following
violations of bile pigments
metabolism:
A) in the blood – the
unconjugated bilirubin
concentration is increased and the
conjugated bilirubin appears;
B) in the feces – stercobilin
drops;
C) in the urine – stercobilin drops,
the appearance of urobilin and
conjugated bilirubin.

57. Cholelithiasis (pigmental stones)
• Obstructive jaundice is connected with the
obstruction for bile outflow (tumour, cholelithiasis).
• Peculiarities of bile pigments metabolism at this type
of jaundice are as follows:
• in the blood – the conjugated bilirubin usually are
elevated; Blood levels of bile acids often are elevated
in obstructive jaundice.
• Feces – clay colored because of the lack of
bilirubin in the bile;
• Urine - is dark.
• Cholemic syndrome appears at obstructive and
parenchimatous jaundices, when bile comes into
blood. It is caused by bile acids and the main
symptoms are:
1. bradycardia,
2. hypotension,
3. excitability,
4. skin itch.
• Steatorea is a syndrome, which is based on the
violation of digestion and fats absorption. Fats
are excreted with feces. The fat-like vitamins are

58. Comparison of Jaundice Comparison of Jaundice
(Cholestatic & Hepatocelllular)(Cholestatic & Hepatocelllular)
Hepatocellular Cholestasis Infiltration
Disease example Acute viral hep. CBD stone Metastatic tumor
Serum bilirubin
(mg/dL)
4 – 8 6 – 20* Usually <4, often
normal
AST, ALT (U/mL) Markedly inc.,
often 500-1,000
May be sl. Inc., <
200
May be slightly
inc., < 100
Serum ALP 1-2x normal 3-5x normal 2-4x normal
PT Inc. in severe
disease
Inc. in chronic
cases
Normal
Response to
parenteral vit. K
No Yes
*Serum bilirubin > 10 mg/dL is rarely seen with CBD stone and
usually indicates carcinoma.

59. Liver Function Tests: Normal Values & Changes
TestsTests Normal ValuesNormal Values HepatocellularHepatocellular
JaundiceJaundice
UncomplicatedUncomplicated
ObstructiveObstructive
JaundiceJaundice
BilirubinBilirubin
DirectDirect
IndirectIndirect
0.1-0.3 mg/dL0.1-0.3 mg/dL
0.2-0.7 mg/dL0.2-0.7 mg/dL
IncreasedIncreased
IncreasedIncreased
IncreasedIncreased
Increased Increased
Urine bilirubinUrine bilirubin NoneNone IncreasedIncreased IncreasedIncreased
Serum albumin/ Serum albumin/
total proteintotal protein
Alb, 3.5-5.5 g/dLAlb, 3.5-5.5 g/dL
Tot, 6.5-8.4 g/dLTot, 6.5-8.4 g/dL
Albumin Albumin
decreaseddecreased
UnchangedUnchanged
Alk phosAlk phos 30-115 IU/L30-115 IU/L Increased (+)Increased (+) Increased (++++)Increased (++++)
Prothrombin timeProthrombin time INR of 1.0-1.4; 10% INR of 1.0-1.4; 10%
inc. after vit K in 24 inc. after vit K in 24
hrshrs
No response to No response to
parenteral vit. K; parenteral vit. K;
prolongedprolonged
Prolonged but Prolonged but
responds to responds to
parenteral vit. Kparenteral vit. K
ALT, ASTALT, AST ALT: 5-35 IU/LALT: 5-35 IU/L
AST: 5-40 IU/LAST: 5-40 IU/L
Inc. in hepato- Inc. in hepato-
cellular damage, cellular damage,
viral hepatitisviral hepatitis
Minimally increasedMinimally increased

62. What is Hepatitis?What is Hepatitis?
 Inflammation of the liverInflammation of the liver
 Caused by viruses, alcohol, medications, andCaused by viruses, alcohol, medications, and
other toxinsother toxins
 This training will focus on viral hepatitisThis training will focus on viral hepatitis
 Hepatitis A Virus (HAV)Hepatitis A Virus (HAV)
 Hepatitis B Virus (HBV)Hepatitis B Virus (HBV)
 Hepatitis C Virus (HCV)Hepatitis C Virus (HCV)
 Hepatitis D Virus (HDV)Hepatitis D Virus (HDV)
 Hepatitis E Virus (HEV)Hepatitis E Virus (HEV)
 Hepatitis F
 Hepatitis G (not confirmed yet).
These viruses all affect the liver but otherwise are unique

63. Acute HepatitisAcute Hepatitis
 Hepatitis can be defined
as a constellation of signs & symptoms resulting from
inflammation & hepatic cell necrosis
 In a previously asymptomatic individual the term
“acute” is applied
 Virus is the most common cause of hepatitis.
 Only occasionally can bacterial infections like
syphilis or TB be considered
 Most cases of acute hepatitis are sub-clinical &
usually undiagnosed

64. Hepatitis A (HAV)Hepatitis A (HAV)
At one time, hepatitis A was referred to as "infectious hepatitis"
because it could be spread from person to person like other viral infections.
Infection with hepatitis A virus can be spread through the ingestion of food
or water, especially where unsanitary conditions allow water or food to
become contaminated by human waste containing hepatitis
 Found in the stool (feces) of personsFound in the stool (feces) of persons
infected with hepatitis A virusinfected with hepatitis A virus
 HAV is usually spread by “fecal-oralHAV is usually spread by “fecal-oral
transmission”transmission”
– Putting something in the mouth (food,Putting something in the mouth (food,
water, hands) that has beenwater, hands) that has been
contaminated with the stool of acontaminated with the stool of a
person with hepatitis Aperson with hepatitis A
– Most infections come from contactMost infections come from contact
with a household member or sexwith a household member or sex
partner who has hepatitis Apartner who has hepatitis A
 Highly infectious and stable inHighly infectious and stable in
environment for monthsenvironment for months

65. Signs andSigns and
Symptoms of HAVSymptoms of HAV
 jaundicejaundice
 fatiguefatigue
 abdominal painabdominal pain
 loss of appetiteloss of appetite
 nauseanausea
 diarrheadiarrhea
 feverfever
Adults have signs and symptomsAdults have signs and symptoms
more often than childrenmore often than children
Incubation Period: 15-50 days
(average 28 days)

66. Hepatitis B (HBV)Hepatitis B (HBV)
Type B hepatitis was at one time referred to as "serum hepatitis," because it was
thought that the only way hepatitis B virus (HBV) could spread was through blood
or serum
About 6-10% of patients with hepatitis B develop chronic HBV infection (infection
lasting at least six months and often years to decades) and can infect others as
long as they remain infected. Patients with chronic hepatitis B infection also are at
risk of developing cirrhosis, liver failure and liver cancer.
 HBV is spread throughHBV is spread through

unprotected sex with an infectedunprotected sex with an infected
personperson

by sharing drugs, needles, orby sharing drugs, needles, or
"works" when using drugs"works" when using drugs

through needlesticks or sharpsthrough needlesticks or sharps
exposures on the jobexposures on the job

from an infected mother to herfrom an infected mother to her
baby during birthbaby during birth
 The best way to protect against HBVThe best way to protect against HBV
isis vaccinationvaccination

67. HBV Structure & AntigensHBV Structure & Antigens
Dane particleDane particle
HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr)
HBcAg = inner core protein (a single serotype)
HBeAg = secreted protein; function unknown

68. There are 4There are 4 open reading framesopen reading frames derived from the same strand (thederived from the same strand (the
incomplete + strand)incomplete + strand)
• SS - the 3 polypeptides of the surface antigen (- the 3 polypeptides of the surface antigen (preS1, preS2 and SpreS1, preS2 and S --
produced from alternative translation start sites.produced from alternative translation start sites.
• CC - the core protein- the core protein
• PP - the polymerase- the polymerase
• XX - a transactivator of viral transcription (and cellular genes?).- a transactivator of viral transcription (and cellular genes?).
HBx is conserved in all mammalian (but not avian) hepadnaviruses.HBx is conserved in all mammalian (but not avian) hepadnaviruses.
Though not essential in transfected cells, it is required for infectionThough not essential in transfected cells, it is required for infection
in vivo.in vivo.
Open Reading Frames

69. Type C hepatitis was previously referred to as "non-A, non-B hepatitis,
Patients with chronic hepatitis C infection are at risk for developing cirrhosis, liver
failure, and liver cancer.
The hepatitis C virus (HCV) usually is spread by shared needles among drug
abusers, blood transfusion, hemodialysis, and needle sticks. Approximately 90% of
transfusion-associated hepatitis is caused by hepatitis C
Hepatitis C (HCV)
Preventing HCV InfectionPreventing HCV Infection
 There isThere is nono vaccinevaccine
 Best prevention is behaviorBest prevention is behavior
changechange
 Do not shoot drugsDo not shoot drugs
 Do not share personal itemsDo not share personal items
such as razors or toothbrushessuch as razors or toothbrushes
 Avoid tattoos or body piercingAvoid tattoos or body piercing

70. Symptoms of HCVSymptoms of HCV
 jaundicejaundice
 fatiguefatigue
 dark urinedark urine
 abdominal pain abdominal pain
 loss of appetiteloss of appetite
 nauseanausea
80% of persons have no signs or symptoms80% of persons have no signs or symptoms
Incubation Period: 14-180 days (average 45 days)Incubation Period: 14-180 days (average 45 days)
• HCV disease does not appear to accelerate HIV diseaseHCV disease does not appear to accelerate HIV disease
• Higher toxicity fromHigher toxicity from Highly Active Antiretroviral TherapyHighly Active Antiretroviral Therapy
((HAART)HAART)
• As people live longer with HIV, manyAs people live longer with HIV, many more HIV deaths aremore HIV deaths are
caused by HCV-related end stage liver diseasecaused by HCV-related end stage liver disease
• There is still a lot of research to be done on these effectsThere is still a lot of research to be done on these effects
Potential Co-Infection Effect ofPotential Co-Infection Effect of HCVHCV on HIV Diseaseon HIV Disease

71. Types D, E, F, and G HepatitisTypes D, E, F, and G Hepatitis
There also are viral hepatitis types D, E, F (not confirmed yet), and G. The most
important of these at present is the hepatitis D virus (HDV), also known as the delta virus
or agent. It is a small virus that requires concomitant infection with hepatitis B to survive.
HDV cannot survive on its own because it requires a protein that the hepatitis B virus
makes (the envelope protein, also called surface antigen) to enable it to infect liver cells.
Hepatitis D OverviewHepatitis D Overview
Caused by hepatitis D virus (HDV)Caused by hepatitis D virus (HDV)
Coined “Delta Hepatitis”Coined “Delta Hepatitis”
Rarely seen in the United StatesRarely seen in the United States
FoundFound onlyonly in persons infected with HBVin persons infected with HBV
and has similar routes of transmission as HBVand has similar routes of transmission as HBV
Prevention is vaccination for HBVPrevention is vaccination for HBV
Hepatitis E OverviewHepatitis E Overview
Caused by hepatitis E virusCaused by hepatitis E virus
Primarily a disease of importPrimarily a disease of import
Very similar to hepatitis A with fecal-oral transmissionVery similar to hepatitis A with fecal-oral transmission
Transmitted like HAV with the same symptomsTransmitted like HAV with the same symptoms
No vaccination available

73. HbsAHbsA
gg
Anti-Anti-
HH
BsBs
Anti-Anti-
HH
BcBc
HBeHBe
AgAg
Anti-Anti-
HH
BeBe
InterpretationInterpretation
++ -- IgMIgM ++ -- Acute HBV, high infectivityAcute HBV, high infectivity
++ -- IgGIgG ++ -- Chronic HBV, high infectivityChronic HBV, high infectivity
++ -- IgGIgG -- ++ Late-acute or chronic HBV infection, lowLate-acute or chronic HBV infection, low
infectivityinfectivity
++ ++ ++ +/-+/- +/-+/- Heterotypic anti-HBs with HBsAg;Heterotypic anti-HBs with HBsAg;
usually indicates chronic HBV carrierusually indicates chronic HBV carrier
statestate
-- -- IgMIgM +/-+/- +/-+/- Acute HBV infection (anti-HBc window)Acute HBV infection (anti-HBc window)
-- ++ IgGIgG -- +/-+/- Recovery from HBV infectionRecovery from HBV infection
-- -- IgGIgG -- +/-+/- Low-level HBsAg carrier or remote pastLow-level HBsAg carrier or remote past
infectioninfection
-- ++ -- -- -- Immunization for HBV (with HBsAg)Immunization for HBV (with HBsAg)

74. Alcoholic HepatitisAlcoholic Hepatitis
 An acute or chronic illness involving the liverAn acute or chronic illness involving the liver
with necrosis, inflammation & scarringwith necrosis, inflammation & scarring
 95% develop a fatty liver which is a reversible95% develop a fatty liver which is a reversible
processprocess
 Encephalopathy & death 20%Encephalopathy & death 20%
 30% go on to cirrhosis within 6 month30% go on to cirrhosis within 6 month
 50% of those abstaining for 6 month recover50% of those abstaining for 6 month recover
completelycompletely

75. Alcoholic HepatitisAlcoholic Hepatitis
SymptomsSymptoms
 Most patients are symptomatic.Most patients are symptomatic.
 The most common complaints are:The most common complaints are:
 Anorexia, nausea, vomitingAnorexia, nausea, vomiting
 Abdominal pain (RUQ)Abdominal pain (RUQ)
 Fever (due to infection or inflammation of liver)Fever (due to infection or inflammation of liver)
 Weight loss due to anorexiaWeight loss due to anorexia
 Jaundice is usually mildJaundice is usually mild
 Diarrhea which is due to portal hypertensionDiarrhea which is due to portal hypertension

76. Alcoholic Liver DiseaseAlcoholic Liver Disease
Characteristics:Characteristics:
1.1. Hepatocyte swelling & necrosisHepatocyte swelling & necrosis
 ballooning due toballooning due to
accumulation of fat, water &accumulation of fat, water &
proteinsproteins
2.2. Mallory bodiesMallory bodies – eosinophilic– eosinophilic
cytoplasmic inclusions incytoplasmic inclusions in
degenerating hepatocytesdegenerating hepatocytes
3.3. Neutrophilic reactionNeutrophilic reaction ––
accumulate around degeneratingaccumulate around degenerating
hepatocytes (“satellitosis”)hepatocytes (“satellitosis”)
4.4. FibrosisFibrosis – (+) activation of– (+) activation of
sinusoidal stellate cells & portalsinusoidal stellate cells & portal
tract fibroblaststract fibroblasts
Alcoholic HepatitisAlcoholic Hepatitis

77. Histological features of
alcoholic hepatitis.
(B) (Black arrows) Mallory
bodies are irregular
eosinophilic cytoplasmic
structures with a rope-like
appearance. (Open
arrow) Ballooning
degeneration of
hepatocytes.

78. Alcoholic Hepatitis
Physical Findings
• Jaundice
• Spider angiomas
• Palmar erythema
• Clubbing of
fingers
• Gynecomastia
• Hepatomegaly
• Splenomegaly
• Pruritis
• Ascites
• Edema
• Caput medusa
• Testicle atrophy
• Dark urine, light

79. Alcoholic HepatitisAlcoholic Hepatitis
Damage to liver causesDamage to liver causes
Hepatic insufficiency:Hepatic insufficiency:
which is responsiblewhich is responsible
for the following:for the following:
– ComaComa
– JaundiceJaundice
– AscitesAscites
– AnemiaAnemia
– Hemorrhagic tendencyHemorrhagic tendency
– Ankle edemaAnkle edema
Hyperestrinism:Hyperestrinism: whichwhich
is responsible for:is responsible for:
– Spider neviSpider nevi
– AlopeciaAlopecia
– GynecomastiaGynecomastia
– Palmar erythemaPalmar erythema
– Testicle atrophyTesticle atrophy

80. Alcoholic Liver DiseaseAlcoholic Liver Disease
1.1. Alcohol through action of alcohol DH & acetaldehydeAlcohol through action of alcohol DH & acetaldehyde
DHDH  excess NADH + Hexcess NADH + H++
 increased lipidincreased lipid
biosynthesisbiosynthesis
2.2. Impaired assembly & secretion of lipoproteins +Impaired assembly & secretion of lipoproteins +
increased peripheral fat catabolismincreased peripheral fat catabolism  fatty liverfatty liver
3.3. Impaired hepatic methionine catabolismImpaired hepatic methionine catabolism  dec.dec.
intrahepatic glutathione (GSH) levelsintrahepatic glutathione (GSH) levels  inc. sensitivityinc. sensitivity
to oxidative injuryto oxidative injury
4. Induction of cytochrome P450
(a) CYP2E1  inc. alcohol catabolism in ER & inc.
conversion of other drugs to toxic metabolites
(b) production of reactive O2 species  damage
membrane hepatocellular dysfunction

81. Alcoholic Liver DiseaseAlcoholic Liver Disease
5. Impaired microtubular and mitochondrial function
6. Alcohol  acetaldehyde  (+) lipid peroxidation 
disrupt cytoskeletal and membrane function
7.7. Become a major caloric sourceBecome a major caloric source  displace other nutrientsdisplace other nutrients
 (+) malnutrition and vitamin deficiencies(+) malnutrition and vitamin deficiencies
8.8. Lead to chronic gastritis, intestinal mucosal damage andLead to chronic gastritis, intestinal mucosal damage and
pancreatitispancreatitis  impaired digestive functionimpaired digestive function
9.9. Induce release of bacterial endotoxin into portal circulationInduce release of bacterial endotoxin into portal circulation
from gutfrom gut  (+) liver inflammation(+) liver inflammation
10.10. Induce release ofInduce release of endothelinsendothelins from sinusoidal endothelialfrom sinusoidal endothelial
cellscells  (+) vasoconstriction & contraction of stellate cells(+) vasoconstriction & contraction of stellate cells 
dec. hepatic sinusoidal perfusiondec. hepatic sinusoidal perfusion  regional hypoxiaregional hypoxia
Alcohol EffectsAlcohol Effects

82. • Occurs in patients who are not heavy drinkersOccurs in patients who are not heavy drinkers
• Strong association withStrong association with obesity, dyslipidemiaobesity, dyslipidemia
and insulin resistance, and overt type 2 DMand insulin resistance, and overt type 2 DM
• Presents only with elevated serum amino-Presents only with elevated serum amino-
transferases and/or GGTtransferases and/or GGT
• (+) accumulation of triglycerides within(+) accumulation of triglycerides within
hepatocyteshepatocytes
• Progress toProgress to non-alcoholic steatohepatitisnon-alcoholic steatohepatitis
(NASH)(NASH)  CIRRHOSISCIRRHOSIS

83. Chronic HepatitisChronic Hepatitis
►Forms:Forms:
 A.A. Chronic Active HepatitisChronic Active Hepatitis::
►Refers to the form of CH were the liver test & histologyRefers to the form of CH were the liver test & histology
are compatible with active & progressive inflammation &are compatible with active & progressive inflammation &
necrosisnecrosis
 B.B. Chronic Persistent HepatitisChronic Persistent Hepatitis::
►Refers to the mild & histological non progressive CHRefers to the mild & histological non progressive CH
where the inflammation is confirmed only to the portalwhere the inflammation is confirmed only to the portal
tracts. The enzymes are normal or only moderatelytracts. The enzymes are normal or only moderately
elevated.elevated.

84. Inherited Chronic LiverInherited Chronic Liver
DisordersDisorders
A. Wilson’s diseaseA. Wilson’s disease
B. HemachromatosisB. Hemachromatosis
C. Alpha 1-antitrypsinC. Alpha 1-antitrypsin
deficiencydeficiency
D. Reye syndromeD. Reye syndrome

85. HaemochromatosisHaemochromatosis
 PathogenisisPathogenisis: A group of: A group of
disorders withdisorders with excessiveexcessive
absorption of iron.absorption of iron.
 The iron is layed down inThe iron is layed down in
liver, heart, pancrease,liver, heart, pancrease,
kidney, & skin (bronzekidney, & skin (bronze
diabetes)diabetes)

Primary is due to mutationPrimary is due to mutation
in the HFE gene, usuallyin the HFE gene, usually
C282YC282Y (cystein is replaced by(cystein is replaced by
tyrosine at amino acid 282)tyrosine at amino acid 282)

Secondary - Iron overloadSecondary - Iron overload ::
• Anemias; Cirrhosis;Anemias; Cirrhosis;
• DietaryDietary

DiagnosisDiagnosis::
• Lethargy, weakness inLethargy, weakness in
men 40-60 y.o.men 40-60 y.o.
• Skin hyperpigmentationSkin hyperpigmentation
• Diabetes 30-60% of pt’sDiabetes 30-60% of pt’s
• arthopathyarthopathy Treatment - phlebotomy

87. Alpha 1-AntitrypsinAlpha 1-Antitrypsin
DeficiencyDeficiency
In children associated liver diseaseIn children associated liver disease
In teenagers & adults, aIn teenagers & adults, a
progressive liver disease withprogressive liver disease with
pulmonary manifestationspulmonary manifestations
Pathogenesis:Pathogenesis: Alpha 1-trypsin is aAlpha 1-trypsin is a
potent protease inhibitor found inpotent protease inhibitor found in
the serum, body fluids, & tissuesthe serum, body fluids, & tissues
It is synthesized by the liver toIt is synthesized by the liver to
protect from tissue injury resultingprotect from tissue injury resulting
from protease like trypsinfrom protease like trypsin

89. Reye’s SyndromeReye’s Syndrome
 An illness seen in the pediatric age groupAn illness seen in the pediatric age group
associated with the fluassociated with the flu
 Symptoms: Nausea, vomiting, hyperactivity,Symptoms: Nausea, vomiting, hyperactivity,
confusion, seizures, & coma, Increasingconfusion, seizures, & coma, Increasing
drowsiness, Belly Painsdrowsiness, Belly Pains
 On liver biopsy there are fatty infiltrationOn liver biopsy there are fatty infiltration
 Chemistry: elevated liver enzymes, NH3Chemistry: elevated liver enzymes, NH3
******NEVERNEVER givegive AspirinAspirin to children withto children with
varicella infection (chicken pox), orvaricella infection (chicken pox), or
during flu sx.!!!!!!!!!!during flu sx.!!!!!!!!!!

90. Occurs in young children with viralOccurs in young children with viral
illness (Varicella or influenza) treatedillness (Varicella or influenza) treated
with Aspirinwith Aspirin
Mechanism: unknown, butMechanism: unknown, but
mitochondrial injury and dysfunctionmitochondrial injury and dysfunction
play an important roleplay an important role

91. REYE'S SYNDROME
• only happens in kids less than 15
years old.
• The cause is unknown, but it is
strongly associated with Aspirin
use during flu's.
• The liver becomes inflamed and
destroyed for unknown reasons.
• It is important because Reye's
syndrome kills about half of kids
who get it.
• NEVER give aspirin containing
medications to your kids under 15
years old for fever control.
• Use Acetaminophen/ Ibuprofen
instead.

92. Hepatic (Liver) FailureHepatic (Liver) Failure
 May result from:
 A. Slow deterioration as part of a chronic progress
 B. Rapid worsening after repeated injuries
 C. catastrophic event such as massive necrosis
 Causes:
 1. Functional liver failure without overt necrosis
 Reye’s syndrome, tetracycline toxicity
 2. Chronic liver disease
 Chronic active hepatitis
 Cirrhosis
 3. Fulminate failure: refers to acute severe
impairment of liver function with encephalopathy &
coma in patients who have had liver disease for less
than 8 weeks

93. Hepatic Failure
• Clinical features:
1. Jaundice
2. Hypoalbuminemia  peripheral edema
3. Hyperammonemia  cerebral dysfunction
4. Fetor hepaticus  “musty” or “sweet & sour” body
odor due to mercaptan formation by action of GI
bacteria on methionine (sulfur-containing)
5. Impaired estrogen metabolism  hyperestrogenemia
(a) palmar erythema – 2º to local vasodilatation
(b) spider angiomas – central, pulsing, dilated arteriole
from which small vessels radiate
(c) hypogonadism & gynecomastia in males
6. Multi-organ system failure - respiratory failure with
pneumonia, sepsis + renal failure  cause of death
7. Coagulopathy - impaired synthesis of factors II, VII, IX and
X  (+) bleeding tendency

95. Hepatic FailureHepatic Failure
• Complications:Complications:
1.1. Hepatic encephalopathyHepatic encephalopathy
 associated with increased blood ammonia levelsassociated with increased blood ammonia levels
 reversible if underlying hepatic condition can be correctedreversible if underlying hepatic condition can be corrected
 features:features:
(a)(a) change in consciousnesschange in consciousness
(b)(b) fluctuating neurologic signs – rigidity, hyperreflexia,fluctuating neurologic signs – rigidity, hyperreflexia,
asterixisasterixis
2.2. Hepatorenal syndromeHepatorenal syndrome
 renal failure in patients with chronic liver diseaserenal failure in patients with chronic liver disease
 main renal functional abnormalities:main renal functional abnormalities:
(a)(a) sodium retentionsodium retention
(b)(b) impaired free water excretionimpaired free water excretion
(c)(c) decreased renal perfusiondecreased renal perfusion
(d)(d) decreased GFRdecreased GFR

96. Hepatic FailureHepatic Failure
• Hepatic encephalopathyHepatic encephalopathy::
– A metabolic disorder of theA metabolic disorder of the
CNS system &CNS system &
neuromuscular system withneuromuscular system with
slight changes in the brainslight changes in the brain
(edema)(edema)
– Clinical FeaturesClinical Features::
• ConfusionConfusion
• Flapping tremorFlapping tremor
(asterixis)(asterixis)
• DrowsinessDrowsiness
• ComaComa deathdeath
Caused by elevated levels ofCaused by elevated levels of
NH3 (ammonia)NH3 (ammonia)

98. CirrhosisCirrhosis
• Most common cause is alcoholic liver disease
• Key features:
1. The parenchymal injury & consequent fibrosis are
diffuse.
2. The nodularity is part of the diagnosis  reflects
balance between regeneration and scarring.
3. Vascular architecture is re-organized by the
parenchymal damage and scarring  formation
of abnormal interconnections

99.  Etiology: triadEtiology: triad

1. necrosis1. necrosis

2. regenerating nodules2. regenerating nodules
 3. fibrosis3. fibrosis
 Categories:Categories:
 MajorMajor
• Alcoholic (#1 cause in western world)Alcoholic (#1 cause in western world)
• Post necroticPost necrotic
 MinorMinor
• Wilson’s diseaseWilson’s disease
• HaemochromatosisHaemochromatosis
• BiliaryBiliary
• Chronic hepatic congestionChronic hepatic congestion
 Budd-Chiari syndromeBudd-Chiari syndrome
• uncommon conditionuncommon condition
Induced by thromboticInduced by thrombotic
or nonthromboticor nonthrombotic
obstruction to hepatic venous outflowobstruction to hepatic venous outflow
 CardiacCardiac
• Right sided heart failureRight sided heart failure
• Tricuspid insufficiencyTricuspid insufficiency
CirrhosisCirrhosis

100. • Pathogenesis:
Progressive fibrosis & re-organization of vascular
micro-architecture of liver
Collagen deposition
(types I & III) in the
lobule
Loss of fenestration of
sinusoidal endothelial
cells
New vascular
channels in the
septae
Create delicate or
broad septal tracts
Impaired hepatocellular
protein secretion
(albumin, clotting factors,
lipoproteins)
Shunting of blood
around the
parenchyma

102. Pathophysiology of CirrhosisPathophysiology of Cirrhosis
Intrahepatic resistanceIntrahepatic resistance Splanchnic BFSplanchnic BF
Portal HPNPortal HPN Systemic HyperkineticSystemic Hyperkinetic
Circulation and HypotensionCirculation and Hypotension
SBPSBP PS-ShuntsPS-Shunts
Activ. NeurohumoralActiv. Neurohumoral
factorsfactors
Variceal formationVariceal formation
Hepatic EncephHepatic Enceph Sodium/Water retentionSodium/Water retention
Pulmonary HPNPulmonary HPN
Hepatorenal SynHepatorenal Syn AscitesAscites
Didier Lubrec MD, AASLD, 2001
Fibrosis

103. Mechanism ofMechanism of
fibrosis andfibrosis and
cirrhosis of thecirrhosis of the
liverliver

104. The characteristic diffuseThe characteristic diffuse
nodularity of the surface reflectsnodularity of the surface reflects
the interplay between nodularthe interplay between nodular
regeneration and scarring. Theregeneration and scarring. The
greenish tint of some nodules isgreenish tint of some nodules is
due to bile stasis.due to bile stasis.
Blind Man’sBlind Man’s
DiagnosisDiagnosis

105. • Complications associated withComplications associated with
cirrhosis:cirrhosis:
1.1. Hepatic failureHepatic failure
a) Multiple coagulation defects
b) Hypoalbuminemia due to decreased
albumin synthesis  pitting edema and
ascites
c) Hepatic encephalopathy
d) Increased serum ammonia due to
defective urea cycle

106. • Complications
associated with
cirrhosis:
2.Portal hypertension
a) Ascites
b) Congestive
splenomegaly
c) Esophageal varices
d) Hemorrhoids,
periumbilical
collateral circulation

107. CirrhosisCirrhosis
ComplicationsComplications
associated withassociated with
cirrhosis:cirrhosis:
3.3. HepatorenalHepatorenal
syndromesyndrome due todue to
decreased renaldecreased renal
blood flowblood flow
4.4. HyperestrinismHyperestrinism inin
malesmales
a)a) GynecomastiaGynecomastia
b)b) Spider angiomasSpider angiomas
c)c) FemaleFemale
distribution of hairdistribution of hair

108. Portal hypertension
Increased pressure in
peritoneal capillaries
Portosystemic
shunting of blood
Splenomegaly
Ascites
Development of
collateral channels
Caput
medusae
Esophageal
varices
Hemorrhoids
Shunting of ammonia
and toxins from the
intestine into the
general circulation
Hepatic
encephalopathy
Anemia
Leukopenia
Bleeding
Thrombocytopenia
Mechanisms of disturbed liver function relatedMechanisms of disturbed liver function related
to portal hypertensionto portal hypertension.

109. Portal hypertensionPortal hypertension
DDevelopment of portal hypertensionevelopment of portal hypertension
Characterized by, that displays byCharacterized by, that displays by
triad signtriad sign::
1)1) ascitesascites, (abdominal [peritoneal], (abdominal [peritoneal]
dropsy),dropsy),
2)2) capute medusaecapute medusae – varicose veins– varicose veins
of front wall of abdomen, veins ofof front wall of abdomen, veins of
gullet (esophagus), and rectal veins,gullet (esophagus), and rectal veins,
3)3) splenomegalysplenomegaly..

111. AscitesAscites Pathophysiology:Pathophysiology:
 Alteration of hepatic blood flow causing portal hypertension.Alteration of hepatic blood flow causing portal hypertension.
 Reduction in liver function:Reduction in liver function:
 Reduction in synthesis of albumin & coagulation proteinsReduction in synthesis of albumin & coagulation proteins
 Reduction in detoxification of bilirubin, ammonia, & drugsReduction in detoxification of bilirubin, ammonia, & drugs
 Complications of ascites:Complications of ascites:
DyspneaDyspnea vomitingvomiting
Decreased cardiac outputDecreased cardiac output hydrothoraxhydrothorax
Anorexia scrotal edemaAnorexia scrotal edema
Reflux esophagitisReflux esophagitis
 Treatment:Treatment:
 Improve hepatic functionImprove hepatic function
 Restrict sodium & fluid intakeRestrict sodium & fluid intake
 Aldactone which inhibits aldosteroneAldactone which inhibits aldosterone
 Paracentesis (removal of fluid with addition of IV albumin)Paracentesis (removal of fluid with addition of IV albumin)
 ShuntsShunts
 Abstain from alcoholAbstain from alcohol
 DiureticsDiuretics
 AldactoneAldactone
 LasixLasix

113. LFT’s/TransaminasesLFT’s/Transaminases
 Transaminases Aspartate-Transaminases Aspartate-ASTAST (SGOT) & Alanine-(SGOT) & Alanine-
ALTALT (SGPT)(SGPT)::
– AST (SGOT)AST (SGOT)
 is normally found in a diversity of tissues including liver, heart,is normally found in a diversity of tissues including liver, heart,
muscle, kidney, and brain. It is released into serum when any onemuscle, kidney, and brain. It is released into serum when any one
of these tissues is damaged.of these tissues is damaged.
– For example, its level in serum rises with heart attacks and with muscleFor example, its level in serum rises with heart attacks and with muscle
disorders.disorders.
 It is therefore not a highly specific indicator of liver injury.It is therefore not a highly specific indicator of liver injury.
– ALT (SGPT)ALT (SGPT)
 is, by contrast, normally found largely in the liver.is, by contrast, normally found largely in the liver.
 This is not to say that it is exclusively located in liver but that isThis is not to say that it is exclusively located in liver but that is
where it is most concentrated.where it is most concentrated.
 It is released into the bloodstream as the result of liver injury.It is released into the bloodstream as the result of liver injury.
 It therefore serves as a fairlyIt therefore serves as a fairly specific indicator of liverspecific indicator of liver

114. AST/ALTAST/ALT

 released into the circulation following hepatocyte injury orreleased into the circulation following hepatocyte injury or
death.death.
The ratio of AST:ALT can be helpfulThe ratio of AST:ALT can be helpful

AST:ALT > 2:1AST:ALT > 2:1 suggestingsuggesting alcoholic liver diseasealcoholic liver disease

AST:ALT < 1:1AST:ALT < 1:1 suggestingsuggesting viral hepatitisviral hepatitis..

They are sensitive, but non-specific for liver damage.They are sensitive, but non-specific for liver damage.

Need isoenzymesNeed isoenzymes

The normal range of values for AST (SGOT) is from 5 to 40The normal range of values for AST (SGOT) is from 5 to 40
units per liter of serum (the liquid part of the blood).units per liter of serum (the liquid part of the blood).

The normal range of values for ALT (SGPT) is from 7 to 56The normal range of values for ALT (SGPT) is from 7 to 56
units per liter of serum.units per liter of serum.
Normal range can vary according to a number of factors, includingNormal range can vary according to a number of factors, including
age and gender.age and gender.

115. AST/ALTAST/ALT
 TheThe highest levels of AST and ALThighest levels of AST and ALT are found withare found with
disorders that cause the death of numerous liver cellsdisorders that cause the death of numerous liver cells
(extensive(extensive hepatic necrosishepatic necrosis).).
 Although, the precise levels of these enzymes do notAlthough, the precise levels of these enzymes do not
correlate well with the extent of liver damage or thecorrelate well with the extent of liver damage or the
prognosisprognosis
 This occurs in such conditions asThis occurs in such conditions as acute viral hepatitisacute viral hepatitis
A or BA or B, pronounced liver damage inflicted by, pronounced liver damage inflicted by toxinstoxins
as from anas from an overdose of acetaminophenoverdose of acetaminophen (Tylenol), and(Tylenol), and
prolonged collapse of the circulatory systemprolonged collapse of the circulatory system (shock)(shock)
when the liver is deprived of fresh blood bringingwhen the liver is deprived of fresh blood bringing
oxygen and nutrientsoxygen and nutrients

116. Serum Alkaline Phosphatase-Serum Alkaline Phosphatase-
(Alk Phos)(Alk Phos)
 Derived from liver, intestines, bones &Derived from liver, intestines, bones &
placenta.placenta.
 Released causing high levels duringReleased causing high levels during
liver damage, particularly necrosis,liver damage, particularly necrosis,
cholestasis/ bile duct obstruction,cholestasis/ bile duct obstruction,
neoplastic,neoplastic,
infiltrative & granulomatous liver disease.infiltrative & granulomatous liver disease.
 Need isoenzymesNeed isoenzymes

117. Pathophysiology Underlying the Symptoms and Signs of Liver Disease
Symptoms/SignsSymptoms/Signs Pathophysiologic MechanismPathophysiologic Mechanism
Weakness, fatigue, anorexia, weight loss, muscle
wasting
Failure of multiple metabolic functions
Fever Liver inflammation, decreased reticuloendothelial
function with increased risk of infection
Bruising, increased bleeding Thrombocytopenia secondary to splenic enlargement,
decreased synthesis of clotting factors 1,11, V, VII,
VIII, IX. And X
Palmar erythema, cutaneous spider
telangiectases, irregular menses,
gynecomastia, impotence, female body hair
distribution in men, testicular atrophy
Altered metabolism of sex hormones, chronic
debilitation
Hepatic encephalopathy Abnormal protein metabolism
Fetor hepaticus Decreased detoxification
Pruritus Decreased bile salt excretion
Cyanosis Arteriovenous shunts in lungs, liver
Jaundice Biliary obstruction, decreased bilirubin synthesis,
decrease bilirubin excretion
Hyperdynamic circulation, wide pulse pressure,
tachycardia
Generalized vasodilation (? Hormonally mediated)
Ascites, peripheral edema Portal hypertension, sodium and water retention, low
serum albumin secondary to decreased hepatic
synthesis
Splenomegaly Portal hypertension

118. Pathophysiology Underlying the Symptoms and Signs of Liver Disease
Symptoms/SignsSymptoms/Signs Pathophysiologic MechanismPathophysiologic Mechanism
Hepatomegaly Cirrhosis (liver may be small), hepatitis, vascular
congestion, bile duct obstruction, infection,
benign infiltrative disease (e.g., fatty liver,
amyloidosis, hemochromatosis), malignant
infiltrative disease (e.g., metastatic cancer,
1ymphoma, large space-occupying lesions such
as neoplasm, abscess)
Varices (esophageal, gastric, rectal, ectopic)
or abnormal abdominal vascular pattern
(caput medusae, umbilical bruit)
Portal hypertension with collateral blood flow
around hepatic blockage
Osteomalacia, hypocalcemia, night
blindness, coagulopathy
Fat-soluble vitamin malabsorption and loss of fat-
soluble vitamine reserves A, D, and K; loss of
vitamin К metabolis (a cofactors for I, II, VII, VIII,
IX, and X)
Anemia Multifactorial: blood loss, chronic disease, vitamin
B12 deficiency splenic sequestration
Leukopenia Hypersplenism secondary to portal hypertension
Hypoglycemia Altered glycogenosis, gluconeogenesis
Hyperglycemia Portosystemic shunting with delayed hepatic
uptake of absorbed glucose
Hypercholesterolemia Obstructive jaundice with decreased cholesterol
excretion

119. ReferencesReferences
1.1. Robbins and Cotran Pathologic Basis of DiseaseRobbins and Cotran Pathologic Basis of Disease 88th edition / Kumar, Abbas, Fautoth edition / Kumar, Abbas, Fauto
20020077.. – Chapter 15. – P. 600– Chapter 15. – P. 600––630.630.
2.2. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.
Banasik // Elsevier Inc, 4th edition. – 2010. – P. 854–903.Banasik // Elsevier Inc, 4th edition. – 2010. – P. 854–903.
3.3. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.
Copyright ВCopyright В.. – Lippincott Williams & Wilkins – 2008. –– Lippincott Williams & Wilkins – 2008. – Chapter 17. – P. 574 – 602.Chapter 17. – P. 574 – 602.
4.4. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, GlennPathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn
Matfin. – New York, Milwaukee. – 2009. – P. 949–974.Matfin. – New York, Milwaukee. – 2009. – P. 949–974.
5.5. General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia:General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia:
Nova Knuha Publishers – 2011. – P.Nova Knuha Publishers – 2011. – P. 546546––566566..
6.6. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott WilliamsEssentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams
& Wilkins), Trade paperback (2003)& Wilkins), Trade paperback (2003) // Carol Mattson Porth, Kathryn J. GaspardCarol Mattson Porth, Kathryn J. Gaspard ––
ССhapter 28. – P. 494–516.hapter 28. – P. 494–516.
7.7. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicineSymeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine
Publishing. – 2010. – P. 434–459.Publishing. – 2010. – P. 434–459.
8.8. Russell JRussell J.. GreeneGreene.. Pathology and Therapeutics for Pharmacists. A basis for clinicalPathology and Therapeutics for Pharmacists. A basis for clinical
pharmacy practicepharmacy practice // Russell JRussell J.. Greene, Norman DGreene, Norman D.. Harris // Published by theHarris // Published by the
Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, LondonPharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London
SE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, USASE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, USA. –. –
Chapter 2. – P. 138–165.Chapter 2. – P. 138–165.
9.9. SilbernaglSilbernagl S.S. Color Atlas of PathophysiologyColor Atlas of Pathophysiology / S./ S. SilbernaglSilbernagl, F., F. LangLang //// ThiemeThieme..
StuttgartStuttgart.. New YorkNew York. –. – 20002000. – P. 162–175.. – P. 162–175.