MODULE 2-3

THE NORMAL CELL

(LIVER CELL MODEL)

The normal cell is a restless microcosm constantly pulsating, modifying its shape
and altering its constitution in response to changing demands and stresses. But unless
these stresses become too severe, the cell tends to maintain a relatively constant or
narrow range of structure that we come to recognize as the norm.

It is important to review the normal structural components of a normal cell to

appreciate the significance of some degenerative changes.

CELL STRUCTURES AND FUNCTIONS

CELL MEMBRANE (PLASMA MEMBRANE OR PLASMALEMMA)

Cell membrane comprises of a lipid bilayer and associated proteins. It functions as

a selective barrier, which determines which substances may enter or leave the cell,
thereby controlling the composition of the cytoplasm. Has interface with environmental
factors (receptors for certain molecules like hormones and neurotransmitter are integral
cell membrane proteins; some membrane proteins are enzymes). Fortification – extrinsic
membrane proteins may strengthen the membrane or hold other membrane proteins in
position.

ORGANELLES OF PROTEIN SYNTHESIS

Protein synthesis is programmed by nuclear DNA and is completed in the cytoplasm.

1. RNA MOLECULES (mRNA, rRNA and tRNA) move through the nuclear pores to
enter the cytoplasm where they collaborate to produce peptides and proteins.

2. RIBOSOMES can be found free in the cytoplasm or attached to the membranes

of the Endoplasmic reticulum. They are the engines of protein synthesis. Their
total number is directly related to the rate of protein synthesis.

3. ROUGH ENDOPLASMIC RETICULUM synthesizes proteins for secretion and

lysosomal enzymes. Also synthesizes proteins, carbohydrates and lipids for
membranes.

4. GOLGI APPARATUS finally processes and packages the newly synthesized

proteins from the rough endoplasmic reticulum.
 59

OTHER MEMBRANOUS ORGANELLES

1. LYSOSOMES - membranous vesicles that contain many different hydrolytic

enzymes for intracellular digestion. Lysosomes in neutrophils are especially well
adapted in killing bacteria while lysosomes in thyroid cells assist in the release
of thyroid hormone.

2. PEROXISOMES (MICROBODIES) - small vesicles that contain oxidative

enzymes including peroxidase and catalase. They are largest and most
numerous in the liver and kidney. They are used for peroxide formation, fatty
oxidation and gluconeogenesis, bactericidal action and detoxification.

3. SMOOTH ENDOPLASMIC RETICULUM - involved in lipid metabolism or

specialized movement of certain ions (calcium, chloride), metabolism of lipid-
soluble substances and glycogen metabolism.

4. MITOCHONDRIA - spherical or ovoid to very elongated, thread like shaped and

are formed of two membranes, one within the other. They are for cellular
respiration, steroid biosynthesis and calcium concentration.

NUCLEUS

Nucleus may be said as the heart or perhaps more properly the brain of the cell.
It is a restricted region containing the genetic material known as deoxyribonucleic acid
(DNA). Its contents, collectively called nucleoplasm are separated from the rest of the
cell, which is the cytoplasm by a double-layered membranous envelope.

1. NUCLEOPLASM contains the chromatin and nucleolus.

2. CHROMATIN consists of DNA and proteins.

3. NUCLEOLUS is a spheroidal structure that is the site of ribosomal RNA (rRNA)

production.

4. NUCLEAR ENVELOPE consists of two membranes that are fused at many points
forming the nuclear pores. It separates the nucleus from the cytoplasm.
DISCUSSION

1. GENERAL ORGANIZATION OF THE LIVER

A. STROMA AND VASCULARITY

The STROMA of the liver comprises primarily of thin connective tissue capsule and
its continuation into portal canals between liver lobules. The liver receives its nutrient
blood supply from the hepatic artery and its functional blood supply from the portal vein.
Blood from the terminal afferent branches of the hepatic artery and portal vein mixes in
the hepatic sinusoids, toxin and other substances from the sinusoidal blood.

1. PORTAL CANALS contain branches of the hepatic artery, portal vein, lymph
vessels and interlobular bile ducts.

a. Interlobular portal venules in portal canals are connected to sinusoids via

distributing venules.

b. Interlobular hepatic arterioles give rise to capillaries that supply the

interlobular connective tissue. They also give rise to capillaries connected to
sinusoids.

c. Lymph vessels that drain the capillaries located in the interlobular connective
tissue running parallel with the blood vessels.

d. Interlobular bile ducts

2. Distinct interlobular septa are present only in pigs.

B. LIVER LOBULES have been defined in different ways.

1. Hepatic lobules (traditional functional subunit of the liver) are roughly

hexagonal columns drained by one central vein. Portal canals lie at angles
of the lobule. Within each hepatic lobule, the polyhedral parenchymal cells are
arranged in anastomosing plates that radiate from a central vein. These plates
are separated from by sinusoids, which receive blood from branches of both
the hepatic artery and portal vein and which drain into the central vein.

2. Portal lobules are triangular columns drained by the bile duct in a portal
canal. The portal canal is the center and a central vein lies at each corner.

3. Liver acinus (anatomic subunit of when the liver is viewed as a bile

secreting gland) comprises the roughly diamond-shaped column supplied by
 61

a terminal branch of the hepatic artery and a corresponding branch of the

portal vein.

2. HISTOLOGIC ORGANIZATION

A. HEPATOCYTES

Hepatocytes are arranged in branching plates that radiate from the terminal
hepatic venule (central vein). Hepatic plates are separated by vascular sinusoids. The
membrane has many specialized features like the microvilli and bile canaliculi formed
between 2 adjacent heptocytes to form a lumen for bile secretion.

1. ORGANELLES AND INCLUSIONS. Hepatocytes contain numerous

mitochondria, abundant rough endoplasmic reticulum and smooth
endoplasmic reticulum, extensive Golgi complexes, lysosomes, peroxisomes,
lipids and glycogen.

a. STORAGE. Carbohydrates are stored in close association with sER in the

form of glycogen, which is broken into glucose when the demand arises.
Lipids are stored as triglycerides in lipid droplets.

b. TOXIFICATION AND INACTIVATION of variety of lipid-soluble drugs

and substances such as barbiturates, antihistamines and steroids are
performed by the sER.

c. BILE SECRETION by hepatocytes involves absorption of blood-borne

components, their conjugation in the sER and excretion in the bile
canaliculi. Bile is composed of water, bile acids, bilirubin, cholesterol
inorganic ions and constituents.

PURPOSES OF BILE SECRETION

1. Excretory – bile is the major route of excretion of many of the body’s

waste products such as surplus cholesterol, bilirubin and metabolized
xenobiotics.

2. Facilitation of digestion – bile acids are the major metabolites of

cholesterol metabolism and the predominant organic solute in the bile.

BILIRUBIN is a metabolic product of the degradation of

hemoglobin, heme protein (myoglobin) and hepatic hemoproteins
(cytochromes).
 Within the Phagocytes

1. The globin portion is degraded and the constituent amino acids are
returned to the amino acid pool.
2. The heme iron is transferred to iron-binding proteins such as
transferring for recycling.
3. The remaining portion of the heme molecule is oxidized by heme
oxygenase to biliverdin.
4. Biliverdin reductase converts biliverdin to bilirubin.
5. Bilirubin is released from the phagocytes into the blood.
6. Before conjugation in the liver, it is bound to albumin to make it more
soluble.

THREE (3) PHASES OF BILIRUBIN ELIMINATION

1. UPTAKE - hepatocytes remove the bilirubin bound to albumin from the

circulation.

2. CONJUGATION – combined with polar molecule such as glucuronic

acid to make bilirubin diglucuronide, which is water-soluble and more
easily secreted into the bile.

3. SECRETION – conjugated bilirubin is transported into the bile

canaliculus for delivery into the bile ductular system.

Within the Gastrointestinal Tract

1. Conjugated bilirubin is converted to urobilinogen by bacteria

2. Fraction of urobilinogen is reabsorbed from the ileum into the portal
blood and returned to the liver by the enterohepatic circulation.
3. Majority of urobilinogen that is absorbed from the gastrointestinal tract
is resecreted into bile.
4. Urobilinogen is freely filtered through the glomerulus because of its low
molecular weight, so it is found in the urine in little concentration.
5. Urobilinogen that is not absorbed from the intestines becomes oxidized
to stercobilin responsible for the color of the feces.

d. SYNTHESIS OF PLASMA PROTEINS (albumin and fibrinogen) and

lipoproteins involves the sER, rER and Golgi complex.
 63

B. SINUSOIDS

1. Function for the exchange between blood and parenchyma. Sinusoids are lined
by a discontinuous and porous endothelium with a basal lamina that is
discontinuous or absent. Thus, the fluid portion of blood has free access to
the perisinusoidal space, into which hepatocytes microvilli project.

2. Stellate macrophages (Kupffer cells) are present among the endothelial cells.

3. Perisinusoidal stellate cells (Fat storage cells) are present in the perisinusoidal
space. They are believed to store Vitamin A and give rise to fibroblast.

C. BILIARY SYSTEM

Biliary system commences as canaliculi within the centrilobular (periacinar)

areas of the hepatic lobule. Just outside the limiting plate, canaliculi drain into
cholangioles (Canals of Hering) that are lined by low cuboidal epithelium.
Cholangioles converge into interlobular bile duct located in the portal areas. Bile
then flows into the main hepatic ducts that unite to form the common bile duct
by which bile is carried to the duodenum.

1. Intralobular bile ductules, which are lined with simple squamous epithelium,
drain the bile canaliculi.

2. Interlobular bile ducts, in portal canals are lined by cuboidal to columnar

epithelium and drained the intralobular ductules.

3. Extrahepatic bile ducts

a. The hepatic duct, cystic duct and bile ducts are lined by simple columnar
epithelium, which may contain goblet cells in ruminants. Mucous glands
are present in the lamina propria.

b. The gall bladder (absent in horse and rat) has a highly folded mucosa-
submucosa that forms gland like crypts. The simple columnar epithelium
has a microvillus surface and contains goblet cells in pigs and ruminants.
Mucous or mixed glands are present in ruminants. Diffuse or nodular
lymphatic tissue is often present.
CONSEQUENCES OF HEPATIC DYSFUNCTION AND FAILURE

1. Disturbances of bile flow with resultant hyperbilirubinemia.

2. Hepatic encephalopathy.
3. Metabolic disturbances including hyperammonemia, hypoglycemia and acidosis.
4. Vascular and hemodynamic alterations such as shunting of portal blood into the
systemic circulation thus bypassing the hepatocytes.
5. Cutaneous manifestations such as epidermal necrosis syndrome in dogs and
photosensitization.