Pathophysiology

1. The hepatic
pathology
Associate Professor of Pathophysiology Department
Arsenteva Ekaterina vladimirovna
Ev.arsenteva@yandex.ru
1

2. A hepatic anatomy structure
2

3. The hepatic functions
. 1. A participation in the digestion – the
hepatic produces bile acids which
emulsify lipids in an intestine,
activate the enzymes of a pancreas
(a lipase), a fermentation and a
absorption of liposoluble
substances (Vit. A,D,E,K).
 2. A deintoxication – in a liver we can
observe a formation of nontoxic
tandem connection with glukuronic
and sulphuric acids; an inactivation of
the ammonia, the indole, the
skatoles, the phenols and other
connection arriving from a GIT
(gastrointestinal tract) and from the
outside.
 3. A regulation of a hemostasis
system maintains the equilibrium (a
contents and an activity) – the factors
by a blood coagulation and a blood
anticoagulation systems.
3

4. The hepatic functions
4
 4. A metabolism regulation:
 of a carbohydrates – the participation in a
glycogenesis and in a glycogenolysis, in a
gluconeogenesis.
 of a lipids exchange, the oxidation of lipid
acids, a formation of ketone bodies.
 a protein metabolism – the synthesis of
proteins, including a plasma, their deposition,
their transamination and their deamination, an
synthesis of an urea and a creatine.
 a synthesis of the majority of the enzymes
providing a metabolism
 a deposition and an exchange of many
vitamins (A, PP, D, B, K), a deposition of iron
ions, of a copper, of a zinc, of a manganese,
of a molybdenum.
 5. A hemopoiesis at a fetus
 6. A participation in reactions of the immune
system, because in a liver there are the
phagocytes of Kupffer.
 7. The biliation.
4

5. The general etiology of hepatic diseases
Infectious hepatic damages (viruses, protozoa, bacteria, helminths, mushrooms).
Toxic hepatic damages – the effect of hepatotoxic substances (polycyclic
aromatic hydrocarbons, chlorine - and organophosphorous pesticides, the
ethanol and its substitutes, Phenolums, the bonds of phosphorus, salts of heavy
metals, CCl4, the toxins of a plant origin (a death angel), the hepatotoxic
medicines: anesthetics (Chloroformium), psychoactive (Aminazine), non-narcotic
analgesics (Indomethacinum, Paracetamolum), the antituberculous drugs.
Physical impacts (radiation, mechanical damages).
Nutritional factors (the rising of consumption of animal fats, the deficiency of the
lipotropic factors and proteins).
Disturbance of a liver blood flow: local (a clottage of a liver artery, portal vein,
cirrhosis) and systemic.
Endocrine disorders – are followed by a metabolic disorder (diabetes mellitus,
thyrotoxicosis, etc.)
Tumors (primary and metastasises).
Congenital defects – anomalies of hepatic development (cavernomatosis of a
vena portae), the disturbance of a metabolism (glycogenoses), heriditary enzyme
defect.
Autoimmune processes in a liver.
5

6. The liver failure
The liver failure is the
typical pathological
process which is
characterized by
permanent disturbance of
one, several or all
functions of a liver that is
followed by the
disturbance of vital
organism activity.
6

7. The liver failure forms are alocated
1. by origin:
 hepatocellular - primary damage of hepatocytes
 shunting (collateral) is the disturbance of blood current
in a liver, i.e. its dumping on the portacaval
anastomoses into the general blood circulation
2. by the quickness of its emergence and its
development:
 fulminant
 acute
 chronic
3. by the damage scale:
 partial
 total
4.by the reversibility of hepatocytes damage:
 reversible
 irreversible 7

8. The main reasons of a liver
failure
1-hepatic: the failure caused by the
processes localized in a liver and
biliary tracts:
A) hepatitises (virus, bacterial,
toxic)
B) hepatoses (dystrophias)
C) cirrhosis
D) tumors
E) parasitogenic damages
E) genetic defects
G) stones, inflammatory processes
of the biliary tracts
2-extrahepatic pathological
processes:
A) a shock (including the
postsurgical shock)
B) a cardiac failure
C) a general hypoxia
D) a renal failure
E) a proteinic starvation
E) a hypovitaminosis E
G) a deficiency of a selenium
H) endocrinopathies: an adrenal
insufficiency, a pathology of
parathyroid glands, etc.
I) metastasises of tumors in a liver
8

9. The hepatitis
9

10. The hepatic distrophy
10

11. The cirrhosis
11

12. The hepatic tumor
12

13. The parasitogenic hepatic
damages
13

14. The disturbed circulation
14

15. The general pathogenesis of the liver failure
THE DAMAGING FACTOR
A partial or full
destruction of
membranes + a
rising of their
permeability
Activation of
immune and
autoimmune
reaction in a
liver
The
development
of
inflammatory
The
intensifying
of the free
radical lipid
peroxidation
An exit from
lysosomes
of their
hydrolyzing
enzyme
The massive destruction of
liver cells
LIVER INSUFFICIENSY
Each of this pathogenetic links can be dominant at the certain stage of the liver
failure development. 15

16. The hepatic cell failure -
Cytolysis and necrosis of hepatocytes →↑
in a blood of active enzymes of
alaninaminotranspherases (ALAT),
aspartate aminotransferases (ASAT),
glutaminaminotranspherases (GLAT) of the
marker of cytolytic process
The disturbances of
metabolic hepatic function:
•a protein metabolism
•a carbohydrate metabolism
•a fats metabolism
•a weakening of antitoxic function of a liver
•a weakening of barrier function
•a toxemia
•an imbalance of hormones
16

17. The disturbance of the protein metabolism
A hypoalbuminemia
and a disproteinemia
The development of
edemas and the
formation of an ascites
The augmentation in a
blood and in an urine
of amino acids
A rising of the
ammonia
concentration in a
blood and that leads
to decrease an urea
in a blood
An ammoniacal
toxicosis
The depression of
efficiency of an
amino acids
deamination
An urea
synthesis
suppression
hypocoagulation
A development of a
hemorrhagic syndrome (the
hemorrhages in a tissue, the
escapes of blood ).
It is promoted also by
decrease of an absorption in
an intestine of liposoluble
vitamin K
The inhibition
of hemostasis
system proteins
synthesis
procoagulums
(a prothrombin,
a proaccelerin,
a proconvertin)
The disturbance
of an albumins
synthesis
17

18. The disturbance
of LDL (low density lipoprotein)
metabolism
The disturbance
of HDL (high density lipoprotein)
synthesis
The rising in a blood plasma a
cholesterol level
A fatty hepatosis
And
atherosclerosis
The disturbances of a lipid metabolism
18

19. The suppression
of the glycogenesis
The depression
of the glycogenolysis
efficiency
The disturbances
of glucoses formation
A fasting
hypoglycemia
A hyperglycemia after
meal
The disturbances of the carbohydrate
metabolism
19

20. VITAMINS
Absorption A,D,E,K
↓ transformation of
provitamins in vitamins
(for example, Carotinum
in vitamin A);
Inhibitions of formation of
coenzymes from vitamins
(for example, from
pantothenic acid - acetyl A
coenzyme, from B1
vitamin - a pyruvate
cocarboxylase).
The disturbance
of the metabolism
MINERAL
SUBSTANCES
An iron
A copper
A chrome
The other disturbances of the
metabolism
20

21. The disturbance of the
antitoxic (barrier) hepatic
function
A neutralization depression by the
LIVER:
 a) the intestinal poisons
 b) the toxicant metabolites
 c) the exogenous poisons
The autointoxication
21

22. The disturbance of the
biliation
The JAUNDICES
22

23. The icterus
The JAUNDICE is the
syndrome which is
characterized by yellow
coloring of skin, mucosas
and scleras, by change of
coloring of secrets and
excretas, because there is
an augmentation in a blood
of the bilirubin which is a
sign of the pigmental
exchange disturbance
(bilirubin exchange).
23

24. The bilirubin metabolism
red blood cells
destruction
hemoglobin
a heme
biliverdin
Indirect bilirubin
Direct bilirubin
urobilinogen
stercobilinogen
blood
liver
intestine
erythrocytes
RES cells
Indirect
bilirubin
Direct bilirubin
BLOOD
Indirect
bilirubin
Urobilinogen
Urobilinoge
n
Stercobilinoge
n
Stercobilin in
FECES
Urobilin
(trases)
UREA
Absence of
bilirubin
24

25. The jaundices
The jaundices
hemolitic ("suprahepatic")
mechanical
("subhepatic")
hepatic
25

26. The hepatocellular jaundice
erythrocyte
s
RES
cells
Direct bilirubin
Indirect
bilirubin
BLOOD
Urobilinogen
Urobilinogen
UREA
Direct bilirubin
Urobilin
Stercobilinoge
n
Stercobilin in
FECES 26

27.  the "leaking" through the damaged cellular membrane in a blood of
hepatic transaminases (an aspartate, alaninaminotranspherases, etc.);
 a loss of ability of hepatic cells to enzymatic destruction of the
urobilinigen, arriving on a portal vein, and to development of an
urobilinogenemiya and urobilinogenuriya;
 depression of quantity of a stercobilinogen in excrements.
THE MAIN LINKS OF THE PATHOGENESIS AND IMPLICATION I
STAGE of the HEPATOCELLULAR JAUNDICE
A DECREASE OF THE
ENZYMES ACTIVITY OF
THE UROBILINIGEN
DESTRUCTION
A DAMAGE OF
THE
HEPATOCYTES
MEMBRANES
THE DECREASE
OF THE ACTIVITY
OF GTF *
The
manifestation
UROBILINOGENEMIYA
Increase of
enzymes level in
blood
Increase of
potassium
level in blood
urobilinuria
27

28.  A depression of formation intensity of a direct bilirubin from indirect. "The bilirubinic
conveyor": a protein of hepatocytes – a ligand – a glyukoruniltranspheraza is broken.
 There are in a blood the bile acids (a cholemia). It is promoted by a compression of cholic
capillaries by edematous hepatocytes that complicates a normal evacuation from them of a
bile and creates the conditions for augmentation of its resorption in circulatory capillaries.
 These disturbances are followed by a decrease of a bile entering in the intestine, and we can
observe the depression of a stercobilinogen maintenance in blood and feces (the urine
brightens, and the feces can become almost colourless).
THE MAIN LINKS OF THE PATHOGENESIS AND IMPLICATION II
STAGE of the HEPATOCELLULAR JAUNDICE
An AGGRAVATION OF
ALTERATION OF GTF
(guanosine triphosphate)*
AND OTHERS
ENZYMES
AN INCREASE OF
MEMBRANES
DAMAGE
A PRELUM OF
CHOLIC
CAPILLARIES
The manifestation
A cholehemia A bilirubinuria
Increase of
enzymes level in
blood
A DECREASE OF
UROBILINOGENEMIYA and
UROBILINOGENURIYA
DEGREE
A DEPRESSION OF THE
STERCOBILINOGEN
MAINTENANCE IN THE
BLOOD, URINE, FECES
28

29. A decrease of the activity of the hepatocytes
glukoruniltranspherase, a disturbance of transmembrane transfer
of a direct bilirubin in hepatocytes and to inhibition of a
glyukoronisation processes of a bilirubin.
In a blood: an indirect bilirubin, a direct bilirubin, a stercobilin and
an urobilin, a cholemia, an enzymes level, a potassium level, a
liver failure, a coma.
THE MAIN LINKS OF THE PATHOGENESIS AND IMPLICATION III
STAGE of the HEPATOCELLULAR JAUNDICE
The inactivation of GTF in
a progress
AN INCREASE OF hepatocytes
DAMAGE
The manifestation
An INCREASE OF LEVEL
OF THE INDIRECT
BILIRUBIN IN THE
BLOOD
A DEPRESSION OF A
DIRECT BILIRUBIN
MAINTENANCE IN THE
BLOOD
A cholemia Increase of
enzymes level in
blood
Increase of
potassium
level in blood
THE
UROBILINOGENEMIYA'S/UREMIYA's
DECREASE
A DECREASE OF THE
STERCOBILINOGEN MAINTENANCE IN
BLOOD, URINE, FECES
29

30. The enzymopathic jaundices
a Gilbert's syndrome (a benign familial icterus)
1
a Dubin– Johnson syndrome
2
a Crigler-Najjer syndrome
3
a Rotor syndrome
4
30

31. A GILBERT'S SYNDROME
1. A long rising of the
unconjugated bilirubin level.
2. A depression of the
stercobilinogen level in a
blood, an urine, feces (at
certain patients).
It is an icterus with the disturbance of active capture and transport of an indirect
bilirubin from a blood in a liver cell
31

32. A DUBIN–JOHNSON SYNDROME
1. A rising of the conjugated
bilirubin level in a blood.
2. The expressed content of
the unconjugated bilirubin in
a blood (at the expense of a
decompensation of the
hepatobiliary system).
3. The gastrointestinal
disorders.
This type of an jaundice arises owing to
defect of the enzymes participating in an
excretion of a conjugated bilirubin
through a membrane of a liver cell in
cholic capillaries.
32

33. A CRIGLER-NAJJAR DISEASE
•A rising of maintenance of the
unconjugated bilirubin in a blood
(especially at the first type).
•A depression of a stercobilinogen level in
a blood, an urine and a feces.
•The significant increase in a maintenance
of a bilirubin monoglyukoronid in bile.
•A kernicterus at children (at the first type).
This type of an enzymopathic jaundice
develops owing to deficiency of a
glyukoroniltranspherase which is a key
enzyme of transformation of a free bilirubin
in connected.
33

34. A ROTOR SYNDROME
1. A rising of a maintenance of
the conjugated bilirubin.
2. The augmentation of level
of the general
coproporphyrin in urine
A pigmental hepatosis or the Rotor syndrome is
the hereditary disease caused by a
bilirubinemia without a depression of
enzymatic activity of a liver, but with the
dysfunction of transportation of a bilirubin
from hepatocytes and not ability of its normal
capture by a sinusoidal pole of hepatic cells
34

35. A hemolytic jaundices
erythrocyte
s
RES cells
Indirect
bilirubin
Indirect
bilirubin
Direct
bilirubin
Urobili-
nogen
Urobilinogen
Stercobilinoge
n
UREA
Absence of
bilirubin
Urobilin
Stercobilin in
FECES
BLOOD
35

36. The reasons
INTERNAL AND
EXTRAVASATED
HEMOLYSIS OF
ERYTHROCYTES
HEMOLYSIS OF
ERYTHROCYTES AND
THEIR PRECURSORS IN
BONE MARROW
FORMATION OF EXCESS OF the
UNCONJUGATED BILIRUBIN AT:
• INFARCTS OF TISSUES
•HEMORRHAGES
SYNTHESIS OF the
UNCONJUGATED
BILIRUBIN FROM THE NOT
hemoglobinous HEME IN
THE LIVER AND IN THE
BONE MARROW
The manifestation
THE SIGNS OF ERYTHROCYTES
HEMOLYSIS
THE SIGNS OF THE HEPATOCYTES
DAMAGE
(AT THE CHRONIC CURRENT)
An anemia
A hemic
hypoxia
A gemoglobinuria
UROBILINOGENEMIYA,
- URIYA
A RISING IN THE BLOOD OF
THE UNCONJUGATED
BILIRUBIN LEVEL
THE AUGMENTATION OF
THE STERCOBILIN LEVEL
IN THE BLOOD, THE
URINE, THE FECES
THE SYMPTOMS OF
THE liver failure
THE SYMPTOMS OF
THE
PARENCHYMATOUS
ICTERUS
The main reasons of the hemolytic jaundice
12
36

37. The obstructive jaundice
erythrocyte
s
RES cells
Direct bilirubin
Direct bilirubin
Direct
bilirubin
Obturation
or
compressio
n of
common
bile duct
BLOOD
URINE
Urobilinogen is absent
Stercobilin in
FECES is
absent
indirect
bilirubin
37

38. The main manifestation of the obstructive
jaundice
A cholaemia
syndrome An acholia
syndrome
A high level of
conjugated bilirubin
in a blood
A hyperirritability
and an excitability
A hypercholesterolemia
A skin
itching
a brachycardia
An arterial
hypotension
Steatorhea
А DYSBACTERIOSIS.
INTESTINAL
AUTOINFECTION
AND INTOXICATION
A
polyhypovita
minosis
a light-colored feces
13
38

39. the markers А norm Hemolytic
jaundice
Obstructive
jaundice
Hepatocellular jaundice
Stage I Stage II Stage III
blood
urine
feces
blood
urine
feces
blood
urine
feces
blood
urine
feces
blood
urine
feces
blood
urine
feces
indirect bilirubin
+ - - ↑ - - N - - N - - N - - ↑ - -
direct bilirubin
+ + - N - - ↑ + - - - - ↑ + - ↓ ↓ -
Urobilinogen,
stercobilinogen
+ + + ↑ ↑ ↑ - - - N N N ↓ ↓ ↓ - - -
the bile acids
- - - - - - ↑ + - - - - + + - + + -
the hepatic
enzymes
N - - N - - ↑ + - ↑ + - ↑ + - ↑ + -
39

40. a liver cirrhosis
a classification by the morphological types :
- hepatoportal
- postnecrotic
-biliary
The etiology:
-the consequence of a viral hepatitis
-an alcoholism
-the autoimmune hepatitises
-the disturbance of a metabolism (a hemochromatosis, a failure of alfa-1-
antitrypsin, the glycogenoses)
-the diseases internal and extrahepatic cholic ways (primary and
secondary biliary cirrhosis)
This is a normal liver Тhis is a liver at the cirrhosis
40

41. The cirrhosis pathogenesis – «a chain
reaction»
the necrosis of
hepatocytes
the formation of
cicatrixes
the disturbance of a blood supply of
a liver pulp
the disturbance of a
blood outflow
a formation of a portacaval anastomoses
41

42. The role of lipocytes in development of a liver fibrosis
42

43. The manifestation of the
cirrhosis
 the portal hypertension.
 a hepatomegalia and splenomegalia (the dysfunction of a lien
on elimination from a blood and to destruction of old
formulated elements of a blood (an anemia, a leukopenia, a
thrombocytopenia) becomes perceptible. (The result of
difficulty of a blood outflow and regional hypoxia).
 the ascites
 the hepatocellular jaundice and hemorrhagic diathesis (аn
angiostaxis of the nose mucous and gums, the hypodermic
petechias and hemorrhages).
 a dysproteinemia (a hypoalbuminemia, a hyper-γ-globulinemia),
a rising of activity of hepatic transaminases and concentration
of a direct bilirubin in a blood, ↑ an ESR (erythrosyte
sedimentation rate).
 a pain syndrome (dyskinesia of cholic ways or necrosis of a
liver).
 The liver failure (expressed in different degree) with a
hepatocerebral syndrome.
43

44. a portal hypertension
Portosystemic anasnomosis
•veins of an esophagus, of a
cardial department of a
stomach,
•veins of a forward abdominal
wall (the “Medusa head”),
• hemorrhoidal veins.
44

45. The ascites
45

46. THE COMPLICATIONS OF THE
PORTAL HYPERTENSIA
- a bleeding from varicose veins of an
esophagus, of a stomach, of a rectum
- a liver encephalopathy
46

47. The liver encephalopathy
is an end-stage of a liver failure. It is characterized by the
metabolic disturbances in a brain which are shown by the
disturbance of mentality and motor and vegetative activity
(a neuro and mental syndrome).
The stages of a liver encephalopathy:
- Prodromal
- Precoma
- Stupor
- Coma
The coma is characterized by a loss of consciousness,
by a fading of reflexes, by periodic respiration that lead to death
47

48. The liver coma. Reasons
A shunting coma
An organism intoxication by
metabolism products
and the exogenous
substances, as result of
their hit in the general
blood circulation
The liver
coma
A parenchymal
coma
The intoxication of an
organism is lied with the
damage or death of
appreciable hepatic part,
and also a loss of
disintoxication function.
48

49. A pathogenesis of the hepatic
coma
Etiology
acute
hypoglycemi
a
acidosis intoxication
Ionic
imbalanse
Disorders of
microcirculation
COMA
49

50. The main factors of the neurotoxicity at the hepatic
encephalopathy
An intestinal flora
A tryptophan,
a tyrosine, a
phenylalanine
a tyramine, an
octopamine
An indole,
a skatole
bilirubin
NH3
Inhibition of
synthesis of
Dofaminum and
Noradrenalinum;
serotonin
synthesis
intensifying
a false mediator
The
toxins
A gamma-
aminobutyric
acid
50

51. The hepatic syndromes
The hepato-enteral
syndrome
The hepato-
lienal
syndrome
The disturbances of
an angiotensinogen
formation
The hypotension.
The disturbances of a
kidneys filtration.
An oliguria.
The hepato-renal
syndrome
The disturbance of a
circulation in portal
system,
the dysfunction of a lien
on elimination from a
blood and the destruction
of old formulated
elements of a blood
The disturbance of
cavitary and parietal
digestion, disturbance
of a blood outflow of a
blood from a gastro-
intestinal tract, the
emergence of erosions
of a gastro-intestinal
tract mucosa.
51

52. Thank you for your
attention!
To your success!
Send me your question
Ev.arsenteva@yandex.ru
52