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W6 - Iron Regulation & Liver Function - Coggle Diagram
W6 - Iron Regulation & Liver Function
Functions of Iron in the Body
Component of Hb
Binding of O2 in Hb of RBC for transport
Component of cytochrome & myoglobin
Regulation of Body temp
Muscle activity
Catecholamine (adrenal hormones) metabolism
Immune system
Brain Development & Function
Thyroid Function
Iron in the Body
Total body iron in a 70kg human is about 4g
Maintained by a balance between absorption & body losses in proximal small intestine (duodenum)
Iron Storage
Ferritin
Consists of a protein shell of light & heavy chains surrounding an iron core
Occurs in nearly all body cells & stores iron in a form that is unable to cause oxidative damage
Ferritin in hepatocytes & macrophages provides a reserve of iron that is available for synthesis of Hb & other heme proteins
Hemosiderin
An end point for intracellular storage of iron, formed when ferritin is aggregated & its protein component degraded
Insoluble
Clinical Significance
Iron deficiency & iron overload are major disorders of iron metabolism.
Abnormal distribution of iron or abnormal production of iron-related proteins may play a role in other heritable or acquired disorders
Iron Related Diseases
Iron Deficiency Anaemia
Caused by insufficient dietary intake & absorption of iron, or iron loss from bleeding
Hemochromatosis
Accumulation of iron in the body from any cause
Anemia of chronic disease
Produce massive elevation of IL-6 ,which stimulates hepcidin production & release from the liver
Porphyria cutanea tarda (PCT)
Results from low levels of the enzyme responsible for the 5th step in heme production
Thalassaemias
Inherited blood disorders that result in the abnormal formation of Hb
Megaloblastic anaemia
Anemia that results from inhibition of DNA synthesis during RBC production, due to deficiency of VitB12 and/or folic acid
Hemolytic anemia
Due to hemolysis, the abnormal breakdown of RBCs, either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular)
Physiological Regulation of Erythropoiesis
Tissue O2 levels
EPO
Iron - heme synthesis
Folic acid & VitB12
Nuclear hormones
Measuring Iron Related Parameters
Serum iron
Iron-Binding Capacity
Transferrin saturation
Serum ferritin
Liver
Role
Metabolism
Digestion
Detoxification
Elimination of substances from body
Main types of injury
Hepatocellular (Hepatitis)
Release of liver enzymes into the blood
Intrahepatic cholestasis
Damage to biliary canilculi
Extrahepatic cholestasis
Damage of obstruction of large bile ducts
Mixed
Hepatic & cholestasis (bile) show damage/obstruction
Hepatitis
Inflammation of liver
Mostly caused by infection with hepatic viruses (Hep A, B, C, D, E)
Other causes: toxins, autoimmune, alcohol, metabolic disease
Progression
Acute hepatitis
Chronic hepatitis
Cirrhosis
Jaundice
Yellowish pigmentation of the skin & white of the eyes due to high bilirubin levels
Levels of bilirubin in blood are normally below 1.0 mg/dL (17 umol/L) & levels over 2-3 mg/dL (34 - 51 umol/L) typically result in appearance of jaundice
Liver Function Panel (LFT)
Total Protein
Albumin
Globulins
Bilirubin
Total & conjucated bilirubin are elevated in cholestasis
Elevated total bilirubin - possible pre-hepatic cause
Elevated conjugated bilirubin - liver problem
ALP
Found: Most organs
ALT
Found: Liver
Most specific than AST
Assayed on day
AST
Found: Liver, heart, skeletal muscle, kidney, brain, RBCs
Not highly specific
GGT
(Gamma Glutamyl Transferase)
Alcoholic Liver Disease
(ALD)
Almost all patients will have
elevated liver enzymes
(higher AST than ALT)
Leads to
fatty liver (hepatic steatosis) & alcoholic hepatitis, both reversible
if alcohol abuse is stopped
NAFLD
(Non alcoholic fatty liver disease)
Accumulation of hepatic fat
Mildly
increased ALT
AST, GGT, ALP & ferritin may also be increased
Biopsy
Obesity, fatty liver
NASH
(Non-alcoholic steatohepatitis)
Accumulation of
hepatic fat with inflammation
May progress to fibrosis, cirrhosis & liver failure
Mild but persistent
increased ALT
Biopsy
Haemochromatosis
HFE mutation
Absorb and store too much iron
Excessive storage in Liver - cirrhosis of liver
High ferritin levels
High transferrin saturation