liver functions & jaundice (W1)

Functions of liver

-Protein metabolism:

-Synthesis of albumin, alpha and beta globulins

-Synthesis of coagulation factors

-Synthesis of urea from ammonia

-Carbohydrate metabolism:

-After meals: Glycogenesis and lipogenesis

-During fasting: Glycogenolysis and gluconeogenesis

-Lipid metabolism:

-Synthesis and excretion of cholesterol

-Synthesis and degradation of triglycerides

-Synthesis of lipoproteins

Bile pigments metabolism:

-Uptake, conjugation with glucuronic acid and excretion

-Bile salts metabolism:

-Synthesis from cholesterol and excretion

-Detoxification of drugs and toxins

-Endocrine functions:

-Catabolism of hormones as estrogen, aldosterone and ADH

-Production of somatomedin, angiotensinogen and erythropoietin

-Production of hormone binding proteins

-Activation of Vitamin D

Hematopoietic functions:

-During fetal life and in certain diseases

-Immune functions

-Biosynthesis of 80–90% of innate immune proteins, including complement components

-Kupffer cells, which account for 80–90% of the total population of fixed tissue macrophages, are a critical component of the mononuclear phagocytic system.

-Storage of vitamins and minerals

Diff between ALT AND AST

ALT: Liver specific, cytoplasmic,

AST: liver, heart, muscles, kidneys and brain , a mitochondrric protein that can be raised incasea of muscle injury, MI, HF,…

AST;ALT RATIO

Anti mito ab (AMA) for

PBC

Anti nuclear, smooth muscle (actin), microsomal ab for

Autoimmune hepatitis

Anti neutrophil cytplasmic ab (pANCA) FOR

Primary sclerosing cholangitis

ALP and GGT

Cases if incr and normal

ALP: liver, bone and placenta

GGT: liver only

(If ALP incrr and GGT ince → liver disease eg cholestasis)

(If ALP incrr and GGT normal → bone disease eg pagets)

(If n ALP and incr GGT → ALCOHOLIC)

In peds what happens to ALP

Incr normal physiology

How can we know if ALP incrr due to liver disease (gher l GGT)

Check serum 5 nucleotidase (found in liver)

What does liver cirrhosis do to the blood

Thrombovytopenia

In alvcohol excess ,RBCs are macrocytic

Alpha1 antitrypsin def causes … to the liver

Cirrhosis

IG4 is raised incase of

Pancreatitis and cholangitis

What type of immunoglobulins incr in PBC, autoimmune hepatitis and pancreatitis/cholangitis

PBC —> IgM

Autoimmune haptitis → IgG

Pancreatitis/cholangitis → IgG4

Tests used to detect liver fibrosis

APRI (aspartate aminotransf to platlet ratio)

Fibrotest

Hyaluronic acid

Procollagen III

TIMP-1

ELF test

Hepatic stiffness fibroscan (transient elastographyy)

Results

Contraindiations

Affected by

Low freq and amplitude vibrations

If fibrotic → incr stiffness → incr speed

Cant be used in morbid obesity and asites

Affected by inflam tissues and congestion

Radionuclide imag (scintiscanning)

How is it done?

For?

Technetium-labelled substance is taken up by the hepatocytes and excreted rapidly into the biliary system.

 eg. (biliary atresia)

Capsule endoscopy can identify

Small intestinal varices

Contraindications for liver biopsy

-low plts <60×10^9

-ascites

-prolonged INR>1.5

-uncooperative patient

-extrahepatic cholestasis

Complications of liver biopsy

ØMost complications of liver biopsy occur within 24 hours (usually in the first 2 hours). They are often minor and include abdominal or shoulder pain that settles with analgesics. Minor intraperitoneal bleeding can occur but this settles spontaneously.

Rare complications include major intraperitoneal bleeding, haemothorax and pleurisy, biliary peritonitis, haemobilia and transient septicaemia.

Hemobilia def and symptoms

Within .. days of the biopsy

Haemobilia: bleeding into the biliary tree that may reach the duodenem

It produces biliary colic, jaundice and melaena within 3 days of the biopsy.

Bilirubin conjugation

Hemolytic jaundice

Incr in both unconj and conjugated bilirubin, however the unconj incr more (Water insoluble) cant reach urine → normal urine color (since darker urine is caused by conjugated bilirubin )

-incr in conj bilirubin → incr urobilinogen → incr stercobilin → dark stools

-normal AL, transferases and albumin

-serum haptoglobin is low

Serum hapttoglobin function

High or low icase of hemolytic cause of jaundice

Haptoglobin catches free HB

Incase of hemolysis → incr free hb → haptoglobin are working → low haptogloobins in case of hemolysis

Gilbert vs crigler najjarr

Gilbert:

-Reduced levels of UDP glucuronosyl transferase (UGT1A1 promotor gene mutation)

-normal reticulocyte count to exclude hemolysis

Crigler

Type1: absence of UGT → AR

Type2: decr UGT → AD

Dubin johnson and rotors syndromes

-conjugated bilirubin problem

-defects in bilirubin handling

-AR

-liver is black in dubin johnson

Benign recurrent intrahepatic cholestasis

-AR

-doesnt progress to chronic liver disease

-BRIC1 caused by ATP8B1 mutation

BRIC2 caused by ABCB11 mutation

-jaundice, pruritis, steatorrhea, weight loss

-may be treated by nsaobiliary drainage

Progressive familial intrahepatoc cholestasis syndrome

-AR

-defective bile acids secrretion → cirrhosis

-3 types

-liver transplant is the only cure

Intrahepatic vs extrahepatic cholestasis

• Extrahepatic cholestasis is due to obstruction of bile flow at any point in the biliary tract distal to the bile canaliculi.

• Intrahepatic cholestasis occurs because of failure of bile secretion, which may be caused by intrinsic defects in bile secretion or inflammation in the intrahepatic ducts.

ØClinically, in both types, there is jaundice with pale stools and dark urine, and the serum bilirubin is conjugated (Cholebilirubin is prevented from reaching the intestine so it regurgitates into blood à increased direct and total bilirubin –> Cholebilirubin appears in urine à dark urine

ØBile salts regurgitates into blood à pruritus and bradycardia

Bile does not reach intestine à pale sools and steatorrhea

When bile salts regurgitate into blood, cause …?

Pruritis and bradycardia

When bile salts dont reach intestines

Pale stools and steatorrhea

Main quest asked for HAV

Outbreak of jaundicE

TRAVELING HISTORY

Liver surface in hepatitis vs cancer/ cirrhosis

A smooth, tender liver is seen in hepatitis and in extrahepatic obstruction,

but a knobbly, irregular liver suggests metastases or cirrhosis.

Spenomegaly indicates

Portal HTN

Tipped spleen indicates

Viral hepatitis

Intrahepatic vs extrahepatic in AST,ALTM,ALP,..

AST AND ALT INC IN INTRAHEPATIC

ALP INCR IN EXTRAAHEPATIC

Pt and albumin n longstanding liver disease

Pt prolonged

Serum albumin is low

2 most useful tests in jaundice

Virial markers

US (mainly to check for extrahepatic obstruction)

In hemolytic jaundice

Reticulocytes incr or dec

Incr

Leucopenia in?

Viral hepatitis

Main ques for HBV and HCV

-country of origin (B+C)

-IV drug users, injections tattoos (B+C)

-men having sex with men / female sex workers

R ratio is

If AL/ALP (R<2) investigations

-US +-CT, MRI ..

-liver biopsy +- genetic study

-MRCP

-AMA. ANA. IgG4

If AL/ALP (R>5) investigations

-abdominal US

-liver biopsy

-viral markers

-autoimmune profile

-metabolic disorders and hereditary (WILSON, A1AT , HH)