Download 4.2.1 Excretion part 1 – The liver

OCR A2 UNIT F214 EXCRETION and THE
LIVER
4.2.1 Excretion part 1
Specification Statements:

Define the term excretion

Explain the importance of removing metabolic wastes, including
carbon dioxide and nitrogenous waste, from the body

Describe, with the aid of diagrams and photographs, the histology
and gross structure of the liver

Describe the formation of urea in the liver, including an outline of
the ornithine cycle

Describe the roles of the liver in detoxification

Definition of Excretion
Excretion is the removal of metabolic waste products from the body
Main Metabolic Waste Products


Carbon dioxide from decarboxylation reactions in cell respiration
Nitrogen containing waste products such as urea, ammonia, uric
acid and creatinine. Urea is the main nitrogenous waste in terrestrial
(land based) mammals
Organs Involved in Excretion
1. Lungs for removal of carbon dioxide
2. Liver

For detoxification of ingested toxins

For urea production from excess amino acids
3. Kidney

For filtration of urea from blood plasma
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
For formation of urine containing a high concentration of urea, for
excretion from the body, in solution
Importance of Removing Metabolic Wastes from the Body
Carbon dioxide and nitrogenous waste products are toxic and therefore must
be excreted.
Details of Toxicity of Carbon Dioxide:
1. Excess carbon dioxide in blood plasma may cause respiratory
acidosis
Carbon dioxide dissolved in blood plasma can combine with water to
form carbonic acid. This acid dissociates to form hydrogen and
hydrogen carbonate ions.
CO2 +
H2O


H2CO3
H+
+
HCO3-
The hydrogen ions lower blood plasma pH. Although plasma proteins
buffer pH changes and the medulla oblongata responds to small pH
reductions by causing increased breathing rate, if blood pH drops
below 7.35, respiratory acidosis occurs with slowed breathing,
drowsiness, headache and confusion
2. Increased carbon dioxide reduces the affinity of haemoglobin for
oxygen binding and oxygen transport in red blood cells.
There are two reasons for this effect:

Most of the carbon dioxide that diffuses into red blood cells reacts with
water to form hydrogen carbonate ions and hydrogen ions. The
equations are shown above. In red blood cells, these reactions are
catalysed by carbonic anhydrase. Hydrogen ions compete with oxygen
for binding space to haemoglobin

Also, carbon dioxide in red blood cells, directly combines with
haemoglobin to form carbaminohaemoglobin, a compound that has a
lower affinity for oxygen than haemoglobin
Details of Toxicity of Nitrogen Containing Wastes

Excess amino acids (those in excess of the body’s requirements for
protein synthesis) cannot be stored in the body

The amine group (NH2) is removed from each excess amino acid and
initially forms ammonia. Ammonia is very toxic because it is very
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soluble in body fluids forming an alkaline solution that increases pH
and changes the tertiary structure of proteins (including enzymes)

Ammonia is rapidly converted into urea in the liver. Urea is still
toxic but less toxic than ammonia, because it is less soluble than
ammonia.
The Liver
Location of the Liver
The liver is a large organ situated in the abdomen to the right of the stomach.
When viewed from the front of the body (as in the diagram below) it is located
to the left of the stomach.
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Blood Supply to and from the Liver
The liver receives blood from two sources:

Oxygenated arterial blood via the hepatic artery (a branch of the
aorta)

Venous blood rich in nutrients via the hepatic portal vein that drains
blood directly from the stomach, the pancreas, the spleen, the small
and large intestines
The liver drains blood into the hepatic vein. The hepatic vein transports its
blood into the (inferior) vena cava.
Liver Structure – Gross Structure and Histology (tissue structure)

The liver is made up of several lobes

Each lobe is further divided into cylindrical lobules, separated by
connective tissue
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
In the portal regions [see figures on page 4], blood from branches of
the hepatic artery and hepatic portal vein enters the lobules into wide
capillaries called sinusoids.

Sinusoids receive a mixture of arterial and venous blood to supply
the hepatocytes (liver cells) with oxygen and nutrients

The sinusoids are lined by an incomplete layer of endothelial cells.
This allows blood to reach the hepatocytes, improving gas exchange
and nutrient supply

Blood from the sinusoids drains into venules, branching from the
hepatic vein. These venules are shown in diagrams (b) and (c) on
page 4, in the centre of each lobule and labelled ‘branch of hepatic
vein’.

Hepatocytes synthesise bile from bile salts and bile pigments
(breakdown products of haemoglobin). Bile enters little
channels/canals called canaliculi within the lobules. Bile then drains
into bile ductules which drain into bile ducts. The bile ducts transport
bile to the gall bladder for storage. A bile duct also transports bile from
the gall bladder to the duodenum, where bile salts are important in the
emulsification of fats
Note: you should learn how to label diagrams of liver histology
Liver Cells/Hepatocytes

Hepatocytes are cuboidal cells with many microvilli to increase their
surface areas for absorption and secretion

Hepatocytes are very active cells and have many mitochondria for ATP
synthesis and dense cytoplasm, with other organelles
Functions of the Liver
The liver is metabolically very active and has many important functions. In
this part of the specification, it is only necessary to include detail of the liver’s
role in deamination of excess amino acids and its role in detoxification.
However, you should recall some other functions that are relevant to other
parts of the specification as follows:
1. Temperature Regulation [F214/4.1.1 (f)]
The metabolic rate in the liver is influenced by impulses from the
thermoregulatory centre in the hypothalamus.
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If core body temperature is too low, the liver will increase its metabolic rate
to produce more thermal energy from respiration. If core temperature is too
high, liver metabolic rate will decrease
2. Synthesis of Cholesterol and Bile Salts
Cholesterol is an important lipid that
 Reduces the fluidity of plasma membranes
 Is a component of high density and low density lipoproteins that
transport non-polar lipids in blood plasma
 is the parent molecule needed for the synthesis of steroid
hormones in the body and bile salts
Bile salts are produced by the liver, stored in the gall bladder (a structure
associated with the liver) and released into the duodenum. Bile salts emulsify
fats (break up large fat droplets into smaller ones). This increases the surface
area of the fat droplets for lipase activity
3. Control of Blood Plasma Glucose Concentration [F214/4.1.3
(e)]
Hepatocytes have receptors for the hormones insulin, glucagon and
adrenaline on their plasma membranes. Hepatocytes therefore respond to
these hormones and are involved in controlling blood plasma glucose
concentrations.
Insulin stimulates liver cells to synthesise glycogen from glucose whereas
glucagon and adrenaline stimulate the breakdown of glycogen to glucose,
by liver cells.
4. Urea Formation in the Liver from Excess Amino Acids

Excess amino acids are amino acids in excess of the daily
requirements for protein synthesis

We cannot store excess amino acids in our bodies, since the amine
groups make them potentially toxic

Excess amino acids are deaminated in the hepatocytes (removal of
the amine group). This reaction is an oxidation producing ammonia
and an organic acid that can enter respiration directly (Krebs cycle)
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
Ammonia is very soluble in water and very toxic (increases cell pH
levels). To remove ammonia in hepatocytes, ammonia combines with
carbon dioxide to form urea via the ornithine cycle, as summarised
below. ATP is required for urea synthesis
2NH3
+
CO2

CO(NH2)2
+
H2O
Name each molecule in the reaction above. It is not necessary for
you to learn the chemical equation

The ornithine cycle is shown in more detail on page 8

Urea is also soluble in water but is less toxic than ammonia

Urea is transported from the liver via the hepatic vein into the vena
cava and returned to the heart

Urea is transported to the kidneys in the renal arteries and filtered out
of the blood plasma in the kidneys

Urea is excreted in urine from the kidneys
The Ornithine Cycle
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You don’t need to know about carbamyl phosphate but should
appreciate where ammonia, carbon dioxide and ATP are used and where
water is used and released
Ornithine Cycle from A2 Textbook
5. Detoxification in the Liver
The liver detoxifies many compounds such as:

Hydrogen peroxide produced in cells as a waste product of cell
respiration
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
Ethanol consumed in the diet (detailed below)

Lactate produced from anaerobic respiration in muscle tissue

Medicinal and recreational drugs, such as paracetamol, steroids and
antibiotics
The processes of detoxification may involve reduction (as in hydrogen
peroxide breakdown by catalase enzyme), oxidation (as in ethanol
breakdown), methylation or combination with another compound.
Detoxification of Ethanol


Ethanol is oxidised to ethanal in hepatocyte cytoplasm, using
ethanol dehydrogenase. NAD accepts the hydrogen released
forming reduced NAD

Ethanal is further oxidised to ethanoate (acetate) in mitochondria,
using ethanal dehydrogenase. NAD accepts the hydrogen released
forming reduced NAD

Ethanoate product combines with coenzyme A to form acetyl CoA

Acetyl CoA enters Krebs cycle

Reduced NAD is re-oxidised in mitochondria in oxidative
phosphorylation. This results in ATP synthesis

NAD is also used to oxidise fatty acids for use in respiration. If too
much NAD is used in ethanol detoxification, more fatty acids are
converted to lipids and stored in liver cells. This condition is called
‘fatty liver’ and can result in liver cirrhosis, damage to hepatocytes
and deposition of connective tissue. Liver cirrhosis is common in
alcoholics. The fatty acids are not available for respiration
Detoxification of Lactate

Muscle cells produce lactate when they respire anaerobically
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
Lactate is transported from muscle cells by blood plasma, to
hepatocytes where the following reaction occurs
Lactate

Pyruvate
 Glucose

Hepatocytes metabolise lactate rather than muscle cells because
hepatocytes can tolerate the low pH better than muscle cells.
Hepatocytes also have the enzyme to catalyse the lactate to pyruvate
reaction. (which is?........................................................)

Conversion of lactate also requires oxygen (why?................................)
which is in short supply in anaerobic muscle tissue
The following pages include OCR questions on the liver, structure and
function
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11
12
13
14
(ii) State which one of vessels, A, B or C, would be most likely to
have the highest concentration of
Carbon dioxide……………………………………………………
Oxygen…………………………………………………………….
Insulin……………………………………………………………..
Glucose soon after eating………………………………………….
Glucose 12 hours after eating……………………………………..
Answers to the OCR questions
Page 10 (a) A sinusoid
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B branch of bile duct
C branch of hepatic portal vein
D branch of hepatic artery
Page 11 (d) (i) reduction/oxidation/dehydrogenation/redox
(ii) ethanal
(iii) combines with CoA/forms acetyl CoA
enters Krebs cycle/combines with oxaloacetate
production of ATP
Page 12 (a) (i) A = sinusoid
B = canaliculus
C = branch of hepatic vein
(ii)arrow (in sinusoid) poiting towards C
(iii) bile
Page 13 (a) (i)
(ii)
X = urea
Y = ornithine
converts NH3 to urea
less toxic
(iii) ornithine cycle
Page 14 (a) (i) A = hepatic vein
B = hepatic portal vein
(ii) A, C, B, B, A
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