Homeostasis: the liver and pancreas

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Homeostasisthe liver and pancreas

• CHAPTER 2.2

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Overview

• Mammalian Liver
• Anatomy
• Functions
• Lipid Regulation
• Protein and Amino Acid Regulation
• Blood Sugar regulation
• Bile production
• Other functions
• Chemical classification of Hormones
• Water and lipid soluble hormones
• Hormonal Feedback loop
• Antagonistic Hormones
• Mammalian Pancreas
• Blood sugar regulation

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Liver Bodily Metabolic Centre

• Largest gland in the body with many metabolic and
  regulatory roles
• Lies on the upper right section of the abdominal
  cavity, under the diaphragm
• Receives plentiful blood supply where substances
  are extracted for processing. 2 main vessel-
• Hepatic artery brings oxygenated blood from
  dorsal artery
• Hepatic portal vein bring nutrient rich blood
  from small intestines
• Hepatic vein - Blood from liver is brought back
  to heart via this vein and posterior vena cava.
• Liver cell/hepatocytes are undifferentiated and
  structurally identical.

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• Contains approximately 0.1 millions lobules that
  serve as structural and functional units
• Each lobe contains rows of liver cells

1. Liver artery arm 2. Bile duct 3. Bile duct
arm 4. Portal vein a. Lobe (simplified) b.
Hepatocyte
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Functions of the Liver

• Over 500 functions. Most importantly
• Regulation of lipids
• Lipids used for energy for cellular functions
  (more energy than glucose)
• Liver responsible for proper lipid concentrations
  in the blood.
• Lipids removed from blood by liver cells or
  transported to fat storage areas in the form of
  adipose tissue or lipoproteins for brain and
  nerve tissue synthesis
• Cholesterols removed and some converted to bile
  salts
• Fatty acids conversion to acetyl-coA via fatty
  acid spiral/lipolysis
• Lipid synthesis cholesterol synthesis
  (Mevalonate pathway) and lipogenesis
• Abnormally high lipids arthrosclerosis,
  coronary thrombosis

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Functions of Liver

• Regulation of amino acids and proteins
• Non-essential aa can be synthesised by
  transamination
• Excess aa and proteins cannot be stored in the
  body. Any excess in returned to the liver for
  catabolism through deamination into
  non-nitrogenous and nitrogenous parts (amino
  group - NH2)
• The non-nitrogenous, keto acid is converted into
  glucose in the liver to be stored as glycogen or
  broken down to release heat.
• The nitrogenous ammonia, is potently toxic.
  Hence, it is converted into urea using the urea
  or ornithine cycle
• This is transported by the blood the kidneys for
  excretion

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ATP
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Functions of Liver

• Bile production
• Bile comprises of bile salts and bile pigments
  that is stored in the gall bladder till needed in
  fat digestion
• Bile salts are synthesized from cholesterol
• Bile pigments (yellowish-green) are from the
  incorporation of the by-products of red blood
  cell disassembly
• Gallstones are an accumulation of cholesterol
  crystals that can cause blockage of the
  bile/biliary duct and increase pressure of the
  gall bladder.
• Accumulation stems from bile constituents
  imbalance.

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Functions of Liver

• Regulation of blood sugar level
• Excess glucose is either converted by pancreatic
  insulin for storage as glycogen or broken down
  into H2O CO2 heat
• When the body has excess glucose, glycogenesis is
  the synthesis of glycogen from glucose that is
  stimulated in the presence of the pancreatic
  hormone insulin.
• Prevention of glucose from falling below the
  crucial level is performed by a process called
  glycogenolysis.
• Glycogenolysis is the catabolism of glycogen that
  requires the activation of hepatic enzyme
  glycogen phosphorylase by pancreatic hormone
  glucagon.

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• Hexokinase is stimulated by insulin

• Glycogen phosphorylase is stimulated by glucagon

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Functions of Liver

• Regulation of blood sugar level
• In skeletal muscles, glycogen cannot be converted
  into glucose directly through glucose-6-phosphate
  route as in the liver due to the lack of the
  enzyme glucose-6-phosphotase.
• Instead it is channeled through glycolysis and
  converted into pyruvate. Consecutively, processed
  through aerobiosis or anaerobiosis.
• In anaerobiosis, lactate that will be carried to
  the liver for conversion firstly, to glucose
  and then glycogen using the Cori cycle.

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Cori Cycle
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Functions of Liver

• Thermoregulation
• Liver is large
• Plenty of blood and high metabolic rate
• Hence, easy to release excess heat to maintain
  body temperature.
• Detoxification of blood Kupffer cells
• Elimination of steroids
• Storage of blood
• Formation of red blood cells in foetus
• Production of plasma protein (fibrinogen, albumin
  and globulin)
• Storage of vitamins and minerals

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Chemical Classes of Hormones

• Three major classes of molecules function as
  hormones in vertebrates
• Polypeptides (proteins and peptides)
• Amines derived from amino acids
• Steroid hormones
• Lipid-soluble hormones (steroid hormones) pass
  easily through cell membranes, while
  water-soluble hormones (polypeptides and amines)
  do not
• The solubility of a hormone correlates with the
  location of receptors inside or on the surface of
  target cells

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Fig. 45-3
Water-soluble
Lipid-soluble
0.8 nm
Steroid Cortisol
Polypeptide Insulin
Amine Epinephrine
Amine Thyroxine
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Cellular Response Pathways

• Water and lipid soluble hormones differ in their
  paths through a body
• Water-soluble hormones are secreted by
  exocytosis, travel freely in the bloodstream, and
  bind to cell-surface receptors
• Lipid-soluble hormones diffuse across cell
  membranes, travel in the bloodstream bound to
  transport proteins, and diffuse through the
  membrane of target cells

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Fig. 45-5-2
Fat-soluble hormone
Water- soluble hormone
Transport protein
Signal receptor
TARGET CELL
OR
Signal receptor
Cytoplasmic response
Gene regulation
Cytoplasmic response
Gene regulation
NUCLEUS
(a)
(b)
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Negative feedback and antagonistic hormone pairs

• Hormones are assembled into regulatory pathways
• Hormones are released from an endocrine cell,
  travel through the bloodstream, and interact with
  the receptor or a target cell to cause a
  physiological response
• A negative feedback loop inhibits a response by
  reducing the initial stimulus
• Negative feedback regulates many hormonal
  pathways involved in homeostasis

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Fig. 45-11
Pathway
Example

Stimulus
Low pH in duodenum
S cells of duodenum secrete secretin ( )
Endocrine cell
Negative feedback
Blood vessel
Target cells
Pancreas
Bicarbonate release
Response
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Insulin and Glucagon Control of Blood Glucose

• Insulin and glucagon are antagonistic hormones
  that help maintain glucose homeostasis
• Glucose that is absorbed from the gut into the
  hepatic portal vein, increases the blood glucose
  concentration. This is detected by the pancreas
• The pancreas has clusters of endocrine cells
  called islets of Langerhans with alpha cells that
  produce glucagon and beta cells that produce
  insulin

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Pancreas Endo- and Exocrine Functions

• Lies deep within the abdominal cavity, on the
  posterior of the abdominal wall
• Elongated and somewhat flattened organ with endo-
  and exocrine functions.
• As an exocrine gland, it functions in the
  digestive system due to the secretion of
  pancreatic juice via the ducts to the small
  intestines.
• As an endocrine gland, it function in the
  secretion of hormones (insulin, glucagon and
  somatostatin)
• This is thanks to the cells on the islet of
  Langerhans

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Fig. 45-12-1
Insulin
Beta cells of pancreas release insulin into the
blood.
STIMULUS Blood glucose level rises.
Homeostasis Blood glucose level (about 90 mg/100
mL)
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Fig. 45-12-2
Body cells take up more glucose.
Insulin
Beta cells of pancreas release insulin into the
blood.
Liver takes up glucose and stores it as glycogen.
STIMULUS Blood glucose level rises.
Blood glucose level declines.
Homeostasis Blood glucose level (about 90 mg/100
mL)
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Fig. 45-12-3
Homeostasis Blood glucose level (about 90 mg/100
mL)
STIMULUS Blood glucose level falls.
Alpha cells of pancreas release glucagon.
Glucagon
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Fig. 45-12-4
Homeostasis Blood glucose level (about 90 mg/100
mL)
STIMULUS Blood glucose level falls.
Blood glucose level rises.
Alpha cells of pancreas release glucagon.
Liver breaks down glycogen and releases glucose.
Glucagon
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Fig. 45-12-5
Body cells take up more glucose.
Insulin
Beta cells of pancreas release insulin into the
blood.
Liver takes up glucose and stores it as glycogen.
STIMULUS Blood glucose level rises.
Blood glucose level declines.
Homeostasis Blood glucose level (about 90 mg/100
mL)
STIMULUS Blood glucose level falls.
Blood glucose level rises.
Alpha cells of pancreas release glucagon.
Liver breaks down glycogen and releases glucose.
Glucagon
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Target Tissues for Insulin and Glucagon

• Insulin reduces blood glucose levels by
• Promoting the cellular uptake of glucose
• Slowing glycogen breakdown in the liver
• Promoting fat storage (lipogenesis)
• Glucagon increases blood glucose levels by
• Stimulating conversion of glycogen to glucose in
  the liver
• Stimulating breakdown of fat and protein into
  glucose

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Diabetes Mellitus

• Diabetes mellitus is perhaps the best-known
  endocrine disorder
• It is the failure of glucose homeostasis
• It is caused by a deficiency of insulin or a
  decreased response to insulin in target tissues
• It is marked by elevated blood glucose levels

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Diabetes Mellitus

• Type I diabetes mellitus (insulin-dependent)
  (30) is an autoimmune disorder in which the
  immune system destroys pancreatic beta cells
• Type II diabetes mellitus (non-insulin-dependent)
  (70) involves insulin deficiency or reduced
  response of target cells due to change in insulin
  receptors

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You should now be able to

1. Note the anatomy and function of the liver
   lobules and their components
2. Difference in canaliculi and sinusoid.
3. Distinguish between the major functions of the
   liver especially lipid, protein, amino acids and
   glucose regulation.
4. Describe the difference between water-soluble and
   lipid-soluble hormones
5. Explain how the antagonistic hormones insulin and
   glucagon regulate carbohydrate metabolism
6. Distinguish between type 1 and type 2 diabetes