Transcript Homeostasis: Functions of the liver - mf011

HOMEOSTASIS:
THE LIVER AND PANCREAS
CHAPTER 2.2
Overview

Mammalian Liver


Anatomy
Functions






Chemical classification of Hormones




Lipid Regulation
Protein and Amino Acid Regulation
Blood Sugar regulation
Bile production
Other functions
Water and lipid soluble hormones
Hormonal Feedback loop
Antagonistic Hormones
Mammalian Pancreas

Blood sugar regulation
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.

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
Functions of the Liver

Over 500 functions. Most importantly
 Regulation
 Lipids
of 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
Functions of Liver
 Regulation
of amino acids and proteins
 Non-essential
 Excess
aa can be synthesised by transamination
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
+ ATP
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.
Functions of Liver
 Regulation
 Excess
of blood sugar level
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.


Glycogen
phosphorylase
is stimulated
by glucagon
Hexokinase
is
stimulated
by insulin
Functions of Liver
 Regulation
 In
of blood sugar level
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-6phosphotase.
 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.
Cori Cycle
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

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
Fig. 45-3
Water-soluble
Lipid-soluble
0.8 nm
Polypeptide:
Insulin
Steroid:
Cortisol
Amine:
Epinephrine
Amine:
Thyroxine
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 cellsurface receptors
Lipid-soluble hormones diffuse across cell
membranes, travel in the bloodstream bound to
transport proteins, and diffuse through the
membrane of target cells
Fig. 45-5-2
Fat-soluble
hormone
Watersoluble
hormone
Transport
protein
Signal receptor
TARGET
CELL
Cytoplasmic
response
(a)
OR
Gene
regulation
NUCLEUS
Signal
receptor
Cytoplasmic
response
(b)
Gene
regulation
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
Fig. 45-11
Pathway
–
Example
Stimulus
Low pH in
duodenum
S cells of duodenum
secrete secretin ( )
Endocrine
cell
Blood
vessel
Target
cells
Response
Pancreas
Bicarbonate release
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
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
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)
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)
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
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
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
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
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
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
You should now be able to:
1.
2.
3.
4.
5.
6.
Note the anatomy and function of the liver lobules
and their components
Difference in canaliculi and sinusoid.
Distinguish between the major functions of the liver
especially lipid, protein, amino acids and glucose
regulation.
Describe the difference between water-soluble and
lipid-soluble hormones
Explain how the antagonistic hormones insulin and
glucagon regulate carbohydrate metabolism
Distinguish between type 1 and type 2 diabetes