Cells type

1. Assessment of the liver function
 Major functions of
the liver
 Impaired functions
of the liver
 Liver function tests

2. Liver
85%
hepatocytes
15%
other cells
Kupffer cells are derived
from blood monocytes
Stellate cells
(space of Disse)
Liver

3. Functions of Kupffer cells
Uptake Remove Produce
Lipoproteins
and their
catabolism
Age and damaged
RBCs (erythroclastic
function)
Bacteria, viruses
Ag-Ab complexes
Endotoxins
Inflammatory
mediators
(local action
or may be released
into systemic
circulation

4. Functions of Stellate cells
Hepatocytes Kupffer cells
Cytokines
activate
Stillate cells
Myofibroblast
transformed to
matrix components
(eg.collagen)
produce
pathogenic factor
of cirrhosis

5. Functions of
hepatocytes
Storage
Glycogen
Vitamins (A, K, D, B12, Folic
acid)
Minerals (iron as ferritin)
Detoxification
(biotransformation)
Convert endo- and exogenous
toxic substances to
non-toxic (e.g. Ammonia to urea)

6. Functions of
hepatocytes
Metabolic
Carbohydrates: Glucose buffer
function
Lipids:
HDL and VLDL synthesis
CH synthesis and degradation to
bile acids, bile salts
Ketogenesis
Utilization of LPs
Amino acids:
Conversion of amino acids to
ketoacids (AST/ALT)

7. Functions of
hepatocytes
Synthetic
Synthesis of plasma proteins,
coagulation factors,
acute phase proteins, complement
Erythropoietic In intrauterine life: RBCs production

8. Functions of
the hepatocytes
Hormones
Degradation of steroid hormones and
polypeptide hormones
insulin, Ep, NE
Excretory
BDG, BMG, bile salts, bile acids,
cholesterol,
phospholipids into the bile

9. Impaired function
of the liver
Primary damage Secondary damage
(Hepatogenic factors) (Extrahepatogenic factors)
Pathological processes
which cause
directly injury
of the hepatocytes
Pathological processes
which
take place
extrahepatically
but cause secondary
injuryof the hepatocytes
Definition

10. Primary damage Secondary damage
Parazites
Cholestasis
Hepatitis
Direct toxic
effect of
toxins, drugs
Cirrhosis
Cancer (primary &
metastatic)
Hypoperfusion
Hypoxia
Endocrine diseases
Accumulation diseases
(eg. hepatosteatosis,
hemochromatosis,
Wilson's disease)
Hypo-, avitaminosis

12. Function Biochemical testing
Hepatocyte integrity
Plasma enzymes:
AST (sGOT)
ALT (sGPT)
LDH, LDH4 and LDH5
Biliary excretory function
Serum:
Total bilirubin
Direct (CB) bilirubin
Indirect (UCB) bilirubin
Damage of bile canaliculi
Urine:
Bilirubin
Urobilinogen
Plasma enzymes:
ALP
GGT
5'nucleotidase

13. Hepatocyte function
- Synthetic Serum:
Total protein
Albumin
Globulin
A/G ratio
PT (PRO TIME), PRO INDEX
Fibrinogen
- Detoxification Ammonia, urea
- Immune response Immunoglobulins
(IgA, IgM, IgG)

14. Serum albumin
 Is synthesized by hepatocytes only.
 Has a long half-life: 15-20 days (4%
degraded per day)
 Because of this slow turnover the serum
albumin is not a good indicator of acute or
mild hepatic dysfunction, only minimal
changes in serum albumin are seen in
acute liver conditions (eg.drug-induced)

15. Hypoalbuminemia
 Is more common in chronic liver
disorders (e.g.. cirrhosis, severe liver
damage)
 Is not specific for liver disease and
occurs in:
 Protein malnutrition
 Chronic infections
 Nephrotic syndrome, etc.

16. Serum globulins
Synthesis
liver B-cells
alpha-1
alpha-2
beta-
gamma-
gamma-globulins - chronic liver diseases (eg.
chronic hepatitis, cirrhosis)
Specific diagnosis
IgG - autoimmune hepatitis
IgM - primary biliary cirrhosis
IgA - alcoholic liver diseases

17. Coagulation factors
 Are made exclusively in hepatocytes.
 Their serum half-lives are shorter than
albumin: from 6 hours for factor VII to 5
days for fibrinogen
 Because of their rapid turnover
measurement of clotting factors is the
single best test of hepatic synthetic
function and helpful in diagnosis and
prognosis of acute parencymal liver
disease.

18. Prothrombin time, prothrombin
index
 Prothrombin is a protein, produced
by the liver from inactive pre-
prothrombin in the presence of
vitamin K.
 Prothrombin production depends on
adequate vitamin K intake and
absorption.

19. Final step of coagulation
Prothrombin
Pre-prothrombin
liver
vitamin K
Thrombin
factor Xa
Fibrinogen
Fibrin Stable
fibrin clot
Factor XIII
Factor XIIIa

20. Prothrombin time (PT, PRO
TIME) & Prothrombin index
 Definition: PT- is
time required for
clotting of citrated
plasma to which
optimum amounts
of thromboplastin
and Ca2+ are
added.
 Normal: 12-20sec.
Prothrombin
index
(PRO INDEX) PRO TIME (patient)
100%x=
Normal: 80-100%
PRO TIME (donor normal)

21. Interpretation of abnormal
Albumin/Prothrombin Time
 Albumin: Monitors slow changes in liver
 function (month to years)
 Reflects long-term liver
 dysfunction
 Protime: Monitors rapid changes in
 liver function ( hours to
 days/weeks)
 Reflects either short or long-term
 liver dysfunction

22. Serum enzymes
Lab.testing
Isolated increased
of bilirubin;
other LFTs-normal
UCB CB
Gilbert
syndrome
Crigler-Najjar
type I,II
Hemolytic disorders
Dubin-Johnson
Rotor syndrome
Hepatocellular
pattern
Cholestatic
pattern
ALT/AST
elevated out
of proportion
of ALP
ALP elevated
out of
proportion
of ALT/AST
Bilirubin increased
LFTs-abnormal

23. Transaminases
 AST (sGOT) ALT (sGPT)
 Many tissues Liver only
 Cyto-/mito Cito- only
 Enzymes of gluconeogenesis in liver and
synthesis of amino acids from ketoacids
 Require Vit B6 as cofactor
 Blood levels: 20-70 IU/L (depending on
method)

24. Transaminases
Alanine
+
Ketoglutarate
Pyruvate
+
Glutamate
ALT
Aspartate
+
Ketoglutarate
Oxaloacetate
+
Glutamate
AST
AST & ALT assay rate of hepatocytes destruction but NOT number
of hepatocytes left (liver function).

25. Transaminases & alcoholic
liver disease
 Alcoholics have: Vit.B6 (Pyridoxal-5-P) deficiency
 AST is affected less than ALT (AST>>ALT in
blood)
 AST/ALT
Ratio =2,4
P5P synthesis of AST & ALT enzymatic activities
P5P P5P
active enzyme
measured by
laboratory assays
enzymes without P5P poorly
measured by lab. analysis

26. Tests of cholelithiasis/ Reduced Bile
flow
 Enzymes released as
a consequence of
decreased bile flow:
 Alkaline phosphatase
(ALP)
 5’-nucleotidase
 Gama-glytamyl
transpeptidase
Long-standing bile duct obstruction: ALP 1.5 IU/L
Acute bile duct obstruction ALP 0,5 IU/L
Hepato-cellular disease ALP 0.2 U/L

27. ALP
 Not comletely specific because of
isoenzymes in other organs (bone,
intestine, placenta).
 Example: Bone disease, intestinal
obstruction, pregnancy

28. Interpretation of liver tests
 1. Consider nonhepatic causes of
abnormal tests
 2. Examine the pattern of LFT
 1. Cholestatic OR Hepatocellular
 2. Acute OR Chronic
 3. Decompensated OR Mild functional
 function impairment

29. Typical pattern of LFTs in
various liver diseases
Tests
Acute
hepatitis
Cronic
hepatitis
Cirrhosis Cholestasis Cancer
Total
bilirubin
N to N to NN to to
AST/ALT N to N to N to
ALP N to N toN

30. Typical pattern of LFTs in
various liver diseases
Tests
Acute
hepatitis
Cronic
hepatitis
Cirrhosis Cholestasis Cancer
Albumin N to NN to
Globulin
PRO TIME N to N to
N N to
N NN
N to N to
Igs Ig G
IgA
Ig G
IgA
Ig M
N