Download phys Learning Objectives Chapter 70 [10-31

Jimmy Kimber
LECOM – Seton Hill OMS1
Physiology Chapter 70: The Liver as an Organ
Learning Objectives
1. Describe the physiologic anatomy of the liver
Functional Unit: Liver Lobule – a cylindrical structure numbering about 50,000-100,000
The lobule contains a central vein that goes to the hepatic veins to the vena cava.
Central vein  hepatic vein  vena cava
The liver lobule is composed of many liver cellular plaes that radiate from the central vein like
spokes of a wheel. Each plate is 2-cells thick and between each are small bile canaliculi that
empty into bile ducts in the fibrous septa.
In the septa are small portal venoules that flow into flat branching hepatic sinusoids. The septa
also contain hepatic arterioles that supply arterial blood to the tissues between the adjacent
lobules and empty directly into the hepatic sinusoids. The venous sinusoids also contain two
other types of cells: endothelial cells and large Kupffer cells.
Lymph: beneath the endothelial lining of the sinusoidsare narrow spaces called spaces of Disse
(also perisinusoidal spaces). These connect with lymphatic vessels.
2. Describe hepatic flow and resistance. How does cirrhosis affect these?
The liver has high blood flow: about 1050 mL of blood each minute. The liver has low vascular
resistance. The pressure leading in the portal vein leading into the liver averages about 9
mmHg, and the pressure in the vena cava is 0 mmHg. Thus, resistance is very low.
Cirrhosis: liver parenchymal cells are destroyed and replaced with fibrous tissues that constrict
around the blood vessels. This greatly increases the resistance. Occasionally, the portal system
is blocked by a large clot that develops in the portal vein or one of its branches. The result is
portal hypertension and the patient usually dies because of excessive loss of fluid from the
capillaries into the lumens and walls of the intestines.
Cirrhosis is caused by alcoholism but also by ingestion of poisons like CCl4, viral diseases like
hepatitis, obstruction of the bile ducts, and infectious processes in the bile ducts.
Jimmy Kimber
LECOM – Seton Hill OMS1
3. How is the liver a blood reservoir?
The liver is an expandable organ, and blood can be stored in its blood vessels. It normally holds
about 450 mL (10% of the body’s blood volume). When pressure is high in the right atrium, the
liver expands, and 0.5 – 1 L of extra blood can be stored here. This is the case of cardiac failure.
4. Describe lymph flow of the liver
Pores in the hepatic sinusoids are very permeable and allow passage of fluid and proteins into
the spaces of Disse. So, the lymphatic flow is high and contains an protein concentration only
slightly less than plasma.
5. What is ascites?
When the pressure in the hepatic veins rises 3- 7mmHg above normal, fluid begins to transudate
into the lymph and leak through the outer surface of the liver capsule directly into the
abdominal cavity. This is almost pure plasma. At vena cava pressures of 10-15 mmHg, hepatic
flow increases up to 20x normal, and the transudation becomes so great that large amounts of
free fluid fill the abdominal cavity – ascites.
6. What factors are involved in liver regeneration?
HGF – hepatocyte growth factor – important for causing liver cell division and growth, it is
produced by mesenchymal cells in the liver and other tissues but not by hepatocytes
IL – 6
TGF-β – transforming growth factor that acts as a potent inhibitor of liver cell proliferation. It is
the main terminator of regeneration.
7. Describe the functions of the liver in carbohydrate and fat metabolism
Carbohydrates:
- Storage of large amounts of glycogen
- Conversion of galactose and fructose to glucose
- Gluconeogenesis
- Formation of chemical compounds from intermediates of metabolism
One of the most important roles of the liver is to buffer glucose concentration
Fat:
- Oxidation of fatty acids to supply energy for other body functions: fatty acids are split by
beta-oxidation into 2-carbon acetyl radicals that form Acetyl-CoA
- Synthesis of large quantities of cholesterol, phospholipids, and most lipoproteins:
cholesterol is converted into bile salts which are secreted in the bile or transported
throughout the body.
- Synthesis of fat from proteins and carbohydrates
8. Describe the functions of the liver in protein metabolism
Jimmy Kimber
LECOM – Seton Hill OMS1
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Deamination of amino acids: required before they can be used for energy or converted into
carbohydrates or fats (also occurs in the kidneys, but to a much less extent)
Formation of urea for removal of ammonia from the body fluids: ammonia is formed by the
deamination process and by bacteria in the gut
Formation of plasma proteins:all of the plasma proteins with the exception of some gamma
globulins are formed by hepatic cells
Interconversions of the various amino acids and synthesis of other compounds from amino
acids: nonessential amino acids, transaminations
9. List and Describe the other functions of the liver
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Storage Site for Vitamins: vitamin A (10 months), vitamin D (3-4 months), vitamin B12 (1
year)
Storage of Iron: liver hepatic cells contain large amounts of apoferritin, which is capable of
combining binding reversibly with iron. Apoferritin-ferritin acts as a blood iron buffer as
well as an iron storage medium.
Liver forms a large proportion of blood substances used in coagulation: fibrinogen,
prothrombin, accelerator globulin, Factor VII, and other factors.
Liver removes or excretes drugs, hormones, and other substances: hormones secreted by
the endocrine glands are also chemically altered or excreted by the liver, including thyroxine
and essentially all the steroid hormones (estrogen, cortisol, and aldosterone).
10. Describe degradation and excretion of heme
Heme is broken into the greenish yellow pigment bilirubin in the following pathway:
Heme  biliverdin  bilirubin  CONJUGATION TO bilirubin glucoronide or bilirubin sulfate 
- Bacteria conjugates bilirubin into urobilinogen (highly soluble) and excreted by kidneys.
Exposure to air changes urobilinogen to urobilin.
- Alternatively in the feces, urobilinogen becomes oxidized to form sterocobilin
11. What is jaundice?
Jaundice is a yellowish tint to the body tissues that includes a yellowness of the skin as well as
the deep tissues. The usual cause of jaundice is large qntities of bilirubin in the ECF, either free
or conjugated bilirubin. The normal plasma concentration of bilirubin is 0.5 mg/dl of plasma.
The skin appears jaundiced when the concentration rises above 3x normal (1.5 mg/dl).
Causes: increased destruction of red blood cells, obstruction of the bile ducts or damage to the
liver cells so that even the usual amounts of bilirubin cannot be excreted. There are two types
of jaundice: hemolytic jaundice, and obstructive jaundice.
12. Differentiate between hemolytic and obstructive jaundice
Obstructive:
- Caused by either obstruction of the bile ducts when a gallstone or cancer blocks the
common bile duct, or by damage to hepatic cells. The rate of bilirubin formation is normal,
but the bilirubin formed cannot pass from the blood into the intestines.
- Bilirubin is mostly conjugated type
Hemolytic:
Jimmy Kimber
LECOM – Seton Hill OMS1
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Caused by red blood cells hemolyzed so rapidly that the hepatic cells can’t excrete the
bilirubin as quickly as it is formed. The plasma concentration of free bilirubin rises to above
normal levels. The rate of urobilinogen formation in the intestine is greatly increased.
Differentiating clinically:
- Hemolytic = free bilirubin
- Obstructive = conjugated bilirubin
* Test called “van den Bergh reaction” can differentiate
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Total obstructive jaundice – no bilirubin can reach the intestines to be converted into
urobilinogen by bacteria, so no urobilinogen is reabsorbed by the blood and none can be
excreted by the kidney. Therefore TOTAL UROBILINOGEN IS NEGATIVE
Kidneys can excrete small quantities of conjugated bilirubin but not albumin-bound free
bilirubin. So, in severe obstructive jaundice, significant quantities of conjugated bilirubin
appear in the urine. TEST BY SHAKING URINE SAMPLE AND OBSERVING FOAM –intense
yellow color.