Guyton Physio Ch 70

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The basic functional unit of the liver is the

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liver lobule. The human liver contins 50,000 to 100,000 individual lobules

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Liver lobule is constructed around a

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central vein -> heptaic veins -> vena cava

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The liver cellular plates

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radiate from central vein. Each is usually 2 cells thick.

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Between the cellular plates lie small

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bile canaliculi that empty into bile ducts in the fibrous septa

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In the septa are small portal venules that receive their blood

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mainly from the venous outflow of the GI tract via portal vein.

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from the portal venules, blood flows into

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hepatic sinusoids between hepatic plates and then into the central vein

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Hepatic arterioles are in

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the interlobular septa.

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In addition to the hepatic cells, the venous sinusoids are lined by two other types of cells:

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1) endothelial cells and 2) Kupffer cells (aka reticuloendothelial cells).

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Kupffer cells are

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resident macrophages that line sinusoids

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Beneath the endothelial lining, between the endothelial cells & hepatic cells are narrow tissue spaces called

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the spaces of Disse, aka perisinusoidal spaces

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spaces of Disse connect with

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lymphatic vessels in the interlobular septa. So excess fluid in these spaces is removed through the lymphatics

Front 12

The large pores in the endothelium allow substances in plasma to

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move freely into the spaces of Disse

Front 13

The liver has ___ blood flow and ___ vascular resistance

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The liver has high blood flow and low vascular resistance. 1050 ml of blood flows from portal vein into liver sinusoids each minute & an additional 300 ml flows into the sinusoids from the hepatic artery, averaging 1350 ml/min. 27% of resting cardiac output

Front 14

Cirrhosis of the liver

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when liver cells are destroyed, are replaced with fibrous tissue which contracts around blood vessels. Impedes flow of portal blood through liver.

Front 15

Cirrhosis of liver is usually caused by alcoholism but can also be from

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ingestion of poisons such as carbon tetrachloride, viruses, obstruction of bile ducts & infections in bile ducts

Front 16

If portal system is suddenly blocked by a large clot that develops in the portal vein or major branches, Blood from intestines and spleen is tremendously impeded resulting in

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portal hypertension and increasing the capillary pressure in intestinal wall to 15 to 20 mmHg above normal. Patient often dies within a few hours because of excessive loss of fluid from capillaries into the lumens and walls of the intestines.

Front 17

Liver is expandable & large quantities of ___ can be stored

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Blood can be stored in its blood vessels. Normal blood volume about 450 ml or almost 10% of body's total blood volume

Front 18

With high pressure in the R atrium,

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The liver expands and 1/2 to 1 L of extra blood is occasionally stored in hepatic veins and sinuses. Esp in cardiac failure

Front 19

The lymph draining from the liver usually has a

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high protein concentration and high flow. 1/2 of all the lymph formed in the body under resting conditions arises in the liver

Front 20

When pressure in hepatic veins rises 3-7 mm Hg above normal

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excessive amounts of fluid begin to transude into the lymph and leak through the outer surface of the liver capsule directly into the abdominal cavity. Almost pure plasma (with plasma proteins).

Front 21

At vena caval pressures of 10 to 15 mm Hg, hepatic lymph flow increases

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to as much as 20 times normal and the "sweating" from the surface can be so great that is causes large amounts of free fluid in the abdominal cavity "ascites"

Front 22

Blockage of portal flow through the liver also causes high capillary pressures in the entire portal vascular system of the GI tract, resulting in edema of the gut wall and transudation of fluid through the serosa of the gut into the abdominal cavity. aka

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aka "ascites"

Front 23

Partial hepatectomy, in which up to 70% of the liver is removed causes

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the remaining lobes to enlarge and restore the liver to its original size. Rapid. Hepatocytes replicate once or twice.

Front 24

HGF

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hepatocyte growth factor appears to be an important factor causing liver cell division and growth. HGF is produced by mesenchymal cells in the liver & other tissues, but not by hepatocytes.

Front 25

In liver diseases associated with fibrosis, inflammation, or viral infections, the regenerative process of the liver

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is severely impaired

Front 26

A sample of portal vein blood before it enters the liver

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almost always grows colon bacilli when cultured. Blood flowing through the intestinal capillaries picks up many bacteria from the intestines

Front 27

In carbohydrate metabolism, the liver performs:

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1) storage of glycogen
2) conversion of galactose and fructose to glucose
3) gluconeogenesis
4) forms many chemical compounds from intermediate products of carbohydrate metabolism

Front 28

Excess glucose in the blood

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is stored as glycogen in the liver.

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Glucose buffer function of the liver

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When blood glucose concentration falls low, glycogen is broken down. However, excess glucose is stored.

Front 30

Gluconeogenesis in the liver

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gluconeogenesis occurs to a significant extent only when the glucose concentration falls below normal. Then large amounts of amino acids and glycerol from triglycerides are converted into glucose.

Front 31

specific functions of the liver in fat metabolism:

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1) oxidation of FA to supply energy for other body functions
2) synthesis of large quantities of cholesterol, phospholipids and most lipoproteins
3) synthesis of fat from proteins and carbs

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To derive energy from neutral fats,

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the fats first split into glycerol and FA. then FA are split by beta-oxidation into 2-carbon acetyl radicals that form acetyl coenzyme A (acetyl-CoA).

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The acetyl-CoA enters

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the citric acid cycle & then is oxidized for energy.

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Beta oxidation can take place

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in all cells of the body, but it occurs especially rapidly in the hepatic cells.

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Two molecules of acetyl-CoA condenses to form

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acetoacetic acid. A highly soluble acid that passes from hepatic cells into the EC fluid & is then absorbed by other tissues.

Front 36

In the body, the acetoacetic acid

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reconvert the acetoacetic acid into acetyl-CoA and then oxidize it in the usual manner. So the liver is responsible for a major part of the metabolism of fats.

Front 37

about 80% of the cholesterol synthesized in the liver is converted to

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bile salts, which are secreted into the bile. Remainder is transported in the lipoproteins and carried by the blood to the tissue cells everywhere in the body.

Front 38

Phospholipids are

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synthesized in the liver and transported principally in the lipoproteins.

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Both cholesterol and phospholipids are

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used by the cells to form membranes, intracellular structures, and multiple chemical substances for cellular function.

Front 40

Fat synthesis from carbs and proteins

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also occurs in the liver.

Front 41

After fat is synthesized in the liver

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it is transported in the lipoproteins to the adipose tissue to be stored.

Front 42

The most important functions of the liver in protein metabolism:

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1) deamination of amino acids
2) formation of urea for removal of ammonia from body fluids
3) formation of plasma proteins
4) interconversions of the various amino acids and synthesis of other compounds from amino acids

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deamination of amino acids

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is required before they can be used for energy or converted into carbs or fats. small amt in other tissues & kidneys, but mostly in liver.

Front 44

formation of urea by liver

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removes ammonia from body fluids. ammonia is also formed in gut by bacteria and then absorbed into the blood. So if liver does not form urea, the plasma ammonia concentration rises rapidly and results in hepatic coma and death. Shunts (blood away from liver) can cause excessive ammonia in the blood tool.

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essentially all the plasma proteins with the exception of part of the ____ _____ are formed by the hepatic cells

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exception of part of the gamma globulins

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plasma proteins formed by the liver

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accounts for 90%. The remaining gamma globulins are the antibodies formed mainly by plasma cells in the lymph tissue of the body.

Front 47

Plasma protein depletion causes ____ of the hepatic cells

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plasma protein depletion causes rapid mitosis of the hepatic cells and growth of the liver to a larger size. With chronic liver disease, plasma proteins, such as albumin, may fall to very low levels, causing generalized edema and ascites

Front 48

The nonessential amino acids

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can all be synthesized in the liver

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The liver stores vitamins. In greatest quantity are

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vit A. but large quantities of D and B12 are stored as well. Vit A can be stored to prevent deficiency for 10 months. D for 3-4 months. B12 for 1 year to several years

Front 50

Except for the iron in the ________ in blood, the greatest proportion of iron in the body is stored in the liver in the form of ________

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Except for the iron in the HEMOGLOBIN in blood, the greatest proportion of iron in the body is stored in the liver in the form of FERRITIN

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The heptaic cells contain large amounts of a protein called ________ which is capable fo combining reversibly with iron

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apoferritin
(therefore when iron is available in the body fluids in extra quantities, it combines with apoferritin for form ferritin and is stored within the hepatic cells.)

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Blood iron buffer

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apoferritin-ferritin system of the liver

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Substances formed in the liver that are used in the coagulation process include

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fibrinogen, prothrombin, accelerator globulin, Factor VII, and several other important factors. Vit K is req'd by the metabolic processes fo the liver for the formation of several of these substances, especially prothrombin and Factors VII, IX and X. In absence of vit K, the concentrations of all these decrease markedly and this almost prevents blood coagulation

Front 54

The liver can detoxify or exrete into the bile, many drugs including

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sulfonamides, penicillin, ampicillin and arythromycin.

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Several of the hormones secreted by the endocrine glands are either chemically altered or excreted by the liver,

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including thyroxine and essentially all the steroid hormones, such as estrogen, cortisol and aldosterone. Liver damage can lead to excess accumulation of one or more of these & cause overactivity

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Major route for excreting calcium

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secretion by the liver into the bile, then into the gut, then lost in feces

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Bilirubin excretion

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bilirubin is excreted in the bile then eliminated in the feces. It is a major end product of hemoglobin degradation. It provides a valuable tool for diagnosing both hemolytic blood diseases and various types of liver deseases.

Front 58

When RBC become too fragile (120 days) cells rupture. Released hemoglobin is phagocytized by tissue macrophages (reticuloendothelial system) in the body. The hemoglobin is first split into

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globin and heme. The heme gives 1) the free iron which is transported in blood by transferrin and 2) a straight chain for 4 pyrrole nuclei which is the substrate from which bilirubin will eventually be formed.

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The straight chain of 4 pyrrole nuclei which is the substrate from which bilirubin will eventually be formed. The first substance is

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biliverdin. rapidly reduced to free bilirubin which is gradually released from macrophages into the plasma.The bilirubin immediately combines with plasma albumin. This combo is absorbed into hepatocytes.

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Then the bilirubin/albumin is absorbed into the hepatocytes, it is released from the albumin. 80% will be conjugated with glucuronic acid to form

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bilirubin glucuronide. 10% with sulfate to form bilirubin sulfate. 10% with other substances. Then the conjugated bilirubin is excreted from hepatocytes by active transport process into the bile canaliculi and then into the intestines.

Front 61

In the intestines, 1/2 the conjugated bilirubin is converted by bacteria into

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urobilinogen which is soluble. Some is reabsorbed through intestinal mucosa back into blood. Most is re-excreted by liver into the gut but 5% is excreted by kidneys into the urine. In urine, urobilinogen becomes oxidized to urobilin. In feces, altered and oxidized to stercobilin.

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The usual cause of jaundice is

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large quantities of bilirubin in the extracellular fluids, either free or conjugated.

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Normal plasma concentration of bilirubin which is almost entirely the free form, averages .5 mg/dl of plasma. In certain abnormal conditions, this can rise to as high as

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40 mg/dl and much of it can be the conjugated type.

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The skin usually begins to appear jaundiced when the concentration of bilirubin rises to

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about 3 times normal. that is, above 1.5 mg/dl.

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Common causes of jaundice are

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1) increased destruction of RBC with rapid release of bilirubin into the blood.
2) obstruction of the bile ducts or damage to the liver cells so that even the usual amounts of bilirubin cannot be excreted into the gastrointestinal tract.

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Two types of jaundice

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1) hemolytic jaundice
2) obstructive jaundice

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Hemolytic jaundice

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RBCs are hemolyzed so rapidly that hte hepatic cells simply cannot excrete the bilirubin as quickly as it is formed.

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Obstructive jaundice

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Obstruction of the bile ducts (most often occurs when a gallstone or cancer blocks the common bile duct) or damage to the hepatic cells (hepatitis). the rate of bilirubin formation is normal, but the bilirubin formed cannot pass from the blood into the intestines. Here, most biliruin in the plasma becomes the conjugated type rather than the free type.

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Diagnostic differences between hemolytic and obstructive jaundice

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hemolytic jaundice, almost all the bilirubin is in the free form.
In obstructive jaundice, it is mainly in the conjugated form. The van den Bergh reaction can differentiate between the two.

Front 70

In total obstructive jaundice

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tests for urobilinogen in the urine are completely negative. and the stools become clay colored owing to a lack of stercobilin & other bile pigments. Happens because no bilirubin can reach the intestines to be converted into urobilinogen by bacteria. so NO urobilinogen is reabsorbed into the blood and none can be exreted by the kidneys into the urine.

Front 71

The kidneys can excrete small quantities of the highly soluble conjugated bilirubin but not the _____ bilirubin.

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Not the albumin-bound free bilirubin. Therefore, in severe obstructive jaundice, significant quantities of conjugated bilirubin appear in the urine. Shake the urine & observe the yellow foam.