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Liver & liver function tests - Coggle Diagram
Liver & liver function tests
Facts
A. Largest organ in human body
B. In upper right quadrant of abdomen
C. Liver cells:
Hepatocytes/ Parenchymal cells 60%- bile formation, CHO & protein metabolism
Endothelial cells 30% - Kupffer cells lining hepatic sinusoids
The rest 10%- vascular supporting tissues & bile ducts
D. Liver is only organ in body that can regenerate itself.
Functions of liver
Metabolic functions
Carbohydrate metabolism
Lipid metabolism
Protein metabolism
Storage functions
Liver stores glycogen, many vitamins & minerals eg. Vitamin D3, B12 & iron
Excretory functions
Parenchymal liver cells conjugate bilirubin with glucoronic acid & excrete into bile duct
Liver excretes other natural (eg. Cholesterol) & foreign substances into bilary tract
Detoxification
Detoxifies numerous drugs & some excreted in bile
Ammonia enters urea cycle to be conv. to urea
Steroid hormones inactivated by conjugation with glucoronic acid & sulphate in liver & excreted in urine.
Benzoic acid detoxified by conjugation with glycine to form hippuric acid, which is excreted in urine
Hematological
Source of fibrinogen, prothrombin & other clotting factors
Protective
Contains kupffer cells, remove foreign materials
Circulatory
Regulate blood volume by serving a blood storage area
Major liver diseases
Hepatitis
Inflammation of liver due to viral, drugs, toxins, lipid accumulation, autoimmune, poisons, hereditary causes or alcohol intake.
Jaundice
Elevation of bilirubin in blood due to excessive break down of RBC’s, liver disease or obstruction of bile duct. Characterized by hyperbilirubinemia & yellow discoloration of skin & eye sclera with hyperbilirubinemia.
Fibrosis
A wound healing process due to inflammation of liver with formation of extracellular fibrous tissue. Although it could be reversed, if left untreated it could proceed to cirrhosis.
Cirrhosis
Formation of hepatic scars/ nodules due to persistence of fibrosis& is characterized by uncompensated liver with progressive loss of liver function.
Hepatocellular
carcinoma (HCC)
Liver cell cancer nodules due to cirrhosis, viral infection, toxins, etc.
Non Alcoholic
fatty liver &
Non alcoholic
Steato-heapatitis
Liver disorder characterized by excessive build up of lipids & fats on liver. If left untreated turns into NASH which would develop into fibrosis, cirrhosis & HCC
Haemochromatosis
Hereditary disease causing accumulation of iron in body, leading to liver damage & bronzed diabetes
Wilson’s disease
A hereditary disease which causes body to retain copper leading to liver damage & neurological degeneration
Cholestasis
Condition where bile cannot flow from liver to duodenum
Cholelithiasis
Presence of stones in gallbladder or common bile duct due to accumulation of cholesterol & calcium salts
Major pathological changes in liver diseases
May be acute or chronic diseases
Liver- cell damage
Main causes
Infections, mostly viral (hepatitis )
Toxins or drugs such as paracetamol, NSAIDS or Alcohol
Secondary to prolonged bilary obstruction
Effects of liver cell damage
Acute release of intracellular constituents into blood (non functional enzymes)
Sensitive indicators of such damage are plasma levels of enzymes AST(SGOT) &ALT (SGPT) & LDH5
S-GPT/ ALT
Name: Alanine aminotranferase/ Serum glutamic pyurvic transaminase
Mainly in cytoplasm of hepatocytes
Increase in acute liver disease eg. Acute hepatitis / liver da,age from drugs/chemicals. May reach 200-400 U/L
GPT is more marked inc. than GOT in liver disease
Interpretation: Normal values in serum 3-26 IU/L
Inc. activity of SGPT indicate acute liver disease as liver cell damage
S-GOT/ AST
Aspartate aminotransferase or serum glutamic oxaloacetic transaminase
Mainly in mitochondria of liver cells & heart muscle cells
Chronic liver disease as cirrhosis, liver cancer, chronic hepatitis & liver congestion & MI
In myocardial necrosis GOT inc. than GOT
Interpretation: Normal values in serum 4-36 IU/L
Inc. activity of SGOT indicate chronic liver disease or MI
Lactate dehydrogenase isoenzymes
Tetramer & catalyzes conversion of pyurvate to lactate with an unparalleled efficiency depending in type of subunits in each isoenzyme. LDH function gradually fades away as number of H over M chains increase.
LDH 1 (4H subunits) in heart & RBCs
LDH 2 (H3 M) in WBCs, also in heart & RBCs but less than LDH1
LDH 3 (H2 M2) lung tissue
LDH 4 (H M3) WBCs, kidney & pancreas cells, lymph nodes
LDH 5 (M4) found in liver & muscles of skeleton
Cholestasis: intra/extrahepatic
Obstruction of bile duct leading to failure of bile to reach the duodenum, leading to accumulation of some or all substances excreted by this route in plasma
Indicators
ALP (Alkaline Phosphatase)
Present in most tissue but high in
Osteoblasts of bone
Bile canaliculi of liver & small intestinal epithelium
Proximal tubules of kidney
Placenta & breasts during lactation
Leukocytes
Limited in heart & brain
Interpretation:
Normal values: 15-67 IU/L in adults
36-135 IU/L in children due to higher osteoblastic activity during growth of bones
ALP inc. in:
Bone diseases due to abnormal osteoblastic activity
Hyperparathyroidism
Obstructive jaundice either extrahepatic or intrahepatic
Physiologically during growth & during pregnancy & lactation
ALP dec. in:
Severe anemia
Scurvy
Arrested growth in children with cretinism
GGT (y-glutamyltranspeptidase)
Found in cell membranes of many tissues in liver, kidney, ducts, pancreas & bile with highest conc. found in liver.
Ref. Range of CGT 0-30 IU/L
GGT elevated in most disease that cause liver disease, mainly in cholestasis due to obstruction of bile duct
also cause by Alcohol, drugs, phenobarbital & phenytoin
a- & B- globulins due to inc. serum lipoprotein
Inc. in serum y-globulins is smaller
Reduced functioning tissue mass
Liver has great functional reserve & power of regeneration
In acute liver disease: decrease in excretory function & cell damage leading to increased bilirubin & GPT (more than GOT)
In chronic liver disease , dec. in functioning tissue mass resulting in impairment of synthetic & metabolic functions ,
result in dec. plasma albumin & albumin/globulin ratio
meanwhile
prothrombin time is prolonged
because
liver can not synthesize prothrombin & Vit K, also GOT inc.
Prothrombin time (PT)
Test to detect & diagnose
bleeeding disorder/ excessive clotting disorder
Normal value: 11 to 13.5 secs
Deficiency of fat soluble Vit. K
Leads to excessive bleeding & inc. PT
Corrected by parenteral administration of Vit. K
International normalized ratio
Ratio between PT value for patient divided by normal PT value,
Used to monitor blood thinning effect for certain medication eg. Anticoagulant warfarin
Healthy people INR: below 1.5
Warfarin users INR: 2-3 :
Albumin
Protein made by liver for,s 60% of total protein in blood
Maintains osmotic pressure
Tissue nourishment
Transport of drugs
Bilirubin
hormones
vitamins
calcium in blood
Albumin level decline after prolonged liver deterioration (late stage) during cirrhosis & liver cancer
AG ratio 1.5-2.5
in liver / renal disease it is less than 1, due to dec. albumin, inc. globulin
Other common liver function tests
Serum preotein electrophoresis
Gel electrophoresis applied to patient serum to separate major proteins eg. Albumin, a-globulin, B- globulingamma globulin
Evaluation of patients with abnormal liver functions, allows for direct quantification of multiple serum proteins
If y-globulin inc. autoimmune hepatitis
a- globulin alpha-q antitrypsin dificiency which could lead to cirrhosis
Inc. ferritin mean haemochromatosis & correlated with COVID 19npatiemts
Immunology
Blood test for
Virus causing hepatitis
Auto antibodies
5’ nucleotidase specific for cholestasis/damage to intra or extra hepatic billary system, can be substitute for GGT to confirm if inc. ALP is biliary or extra biliary
Blood ammonia
In hepatic encephalopathy (coma) meausure ammonia conc.
Not for all cases of hepatic coma May have other causes
Alpha- fetoprotein
Glycoprotein in developing fetus but decline after birth
In Adult male & non pregnant female, inc. AFP is indication of hepatocellular carcinoma
Normal range adults less than 15ng/ml
The Bile
Hepatic bile:
97% water
1% bile acid
1% Electrolytes
1% Other substances eg. Cholesterol, Phospholipid, bilirubin, proteins eg ALP
Hepatic bile output = 1L/day
A. Bile acids & Salts
Cholesterol —in liver cells—> choroid acid &chenodeoxychoilic acid —conjugate with glycine/taurine—>glycolic acid, taurocholic acid, glycochenodeoxycholic acid , taurochenodeoxyxholic acid —Na+, K+ —> Bile salts
Functions:
Lipid digestion: emuslisification of lipids so inc. SA subjected to pancreatic lipase
Activate pancreatic lipase
Essential for absorption of fat soluble vitamins (A,D, E, K
Hydrotropic effect: render cholesterol in bile more soluble so prevent precipitation of cholesterol in gall bladder so prevent gallstone
B. Bile pigments: mainly bilirubin
Hemoglobin — catabolism in reticuloendothelial cells—> Bilirubin — Combination with albumin—> unconjugated bilirubin
—> carried to liver
In liver conjugated with glucoronic acid via UDP glucuronyl transferase to give conjugated bilirubin, which excreted in bile to intestine, undergo decinjugation & oxidation to form urobilinogen
Urobilinogen partly further metabolised to produce stercobilinogen & stercobilin
give brown color to faeces
Partly reabsorbed & re-excreted in urine as urobilin
DB is water soluble & can appear in urine if
evel increase in blood
Total bilirubin= DB + IB
Jaundice
Hyperbilirubinemia
Clinical manifestations
Yellow discoloration of plasma , skin, sclera & mucous membrane due to bilirubin accumulation
Yellow discoloration apparent when serum total protein reaches 2-3 mg/dL
Hemolytic jaundice : Inc. IB only
Hepatic jaundice: Inc. IB & DB
Obstructive jaundice: Inc. DB only :
Classification
Hemolytic
Prod. Of bilirubin > than excretion by liver cells due to hemolysis
Inc. IB
DB normal
Inc. Total Bilirubin
Inc. Fecal stercobilinogen, urobilinogen
Urinary bilirubin absent
Urine color pale yellow
Stool: Dark
Obstructive
Obstruction of bile ducts leading to deficiency in bilirubin excretion due to gall bladder stones
Normal IB
Inc. DB
Inc. Total bilirubin
Dec. Fecal stercobilinogen & urobilinogen (more than hepatic)
Inc. urinary bilirubin (more than hepatic)
Urine color yellow green (cola color) Darker than hepatic
Stool clay (lighter than hepatic)
Neonatal
Causes: RBC destruction
immature hepatic handling of bilirubin
Result: inc. plasma level of unconjugated bilirubin in new born
Plasma conc. May be as high as 30 mg% & exceed plasma protein binding capacity so free unconjugated May pass BBB & deposit in brain causing kernicterus
Gilbert syndrome
Genetic disorder of bilirubin metabolism characterized by impaired conjugation of indirect bilirubin due to impaired due to
impaired UDP glucoronyltransferase 1A + limited uptake of Unconjugated Bilirubin
5% of population
Responsive to phenobarbital, it inc. UDPGT1A
Crigler- Najjar syndrome Type-I
Very rare, in infants
lacking
UDPGT1A, lead to elevated serum level of IB, pass BBB lead to kernicterus
more fatal than Gilbert, not responsive to phenobarbital
Cringler- Najjar syndrome Type-II
Uncommon, in infants with
partial defect
in UDPGT1A conjugation lead to slight inc. in IB less fatal than type I
responsive to phenobarbital
Dubin- Johnson syndrome
Genetic deficiency in excretion of conjugated bilirubin leading to inc. in conjugated bilirubin in blood. Black pigments in liver tissue w/ inc. coproporphyrin I/III ratio in urine
Jotor syndrome
Rare genetic disorder similar to Dubin Johnson, but mechanistic is still unknown & theres inc. DB in blood without black pigment
Hepatic
Deficiencies in bilirubin metabolism due to liver damage
Inc. IB
Inc. DB
Inc. total bilirubin
Dec. Fecal stercobilinogen & urobilinogen
Inc. urinary bilirubin
Urine color: Orange yellow
Pale stool
Enzymes in specific diseases
Acute hepatitis, viral hepatitis
^ AST
^^^ ALT
^ ALP
^ GGT
Albumin normal
^ Bilirubin
Alcoholic hepatitis
^ AST
^^ ALT
^ ALP
^^^ GGT
Albumin normal
^ Bilirubin
Chronic hepatitis
^^^ AST
^ ALT (less than AST)
^ ALP
^ GGT
Albumin normal/ starting to dec.
^ Bilirubin
Cirrhosis/ severe chronic
^^ AST
^ ALT (less than AST)
^ ALP
^ GGT
Albumin low, inverted A/G ratio
^ Bilirubin
Cholestasis
^ AST
^ ALT
^^^ ALP
^^^ GGT
Albumin normal
^ ^Bilirubin DB only
Hepatocellular carcinoma
^ AST
^ ALT (less than AST)
^ ALP
^ GGT
Albumin inverted
^ Bilirubin