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Case 9: Histophysiology (Liver) - Coggle Diagram
Case 9: Histophysiology (Liver)
Liver
Describe the structure of the Liver
Liver is the heaviest gland in the human body, it weighs about 1.4 kg
Liver histologically consists of Stroma and Parenchyma
Parenchyma are also known as the Liver cells called Hepatocytes
Stroma is a capsule of fibrous connective tissue
Stroma is surrounded by a collagen-elastic fibre containing Capsule of Glisson
Stroma has Trabeculae or Septa which are formed by the continuation of the Glisson capsule that extends into the liver and surrounds individual lobules
Glisson Capsule is absent or appears in very small amount in humans and portal tracts
Stroma has a Network of Reticular fibres that surrounds the Hepatocytes and Sinusoids of the Liver
Blood Supply of the Liver
Outline the Blood Supply of the Liver
Liver receives blood from two sources
75% of the Blood is from the Hepatic Portal Vein
25% of the Blood is from the Common Hepatic Artery
Hepatic Portal Vein receives Nutrient-rich, Oxygen-poor blood from the organs of the GIT such as the Stomach, Intestines, Pancreas and Spleen
Nutrients may be endocrine secretions or toxins ingested from the GIT
Hepatic Portal Vein then transports the Nutrient-rich Blood to the Liver
Therefore, the liver is perfectly placed in the body to receive nutrients and detoxify blood
Common Hepatic Artery which is the branch of the Coeliac Trunk of the Thoracic Aorta receives Oxygen-rich Blood from the Aorta
The Common hepatic Artery then transports the Oxygen-rich blood to the liver
Blood from the Common Hepatic artery is used to sustain the Hepatocytes of the liver
Deoxygenated blood produced by the liver is then transported out of the Liver by the Hepatic Vein
Hepatic vein then drain the deoxygenated blood into the Inferior vena Cava
Liver produces Bile, which is released into the Bile Duct
Bile duct then carries the Bile liquid from the Liver to the GIT
Bile in the Liver is transported into the opposite direction to Blood
Blood Supply to the Liver
Describe the movement of blood within the Liver
Liver receives blood from two sources:
Oxygenated blood from the Hepatic Artery
Nutrient-rich, Deoxygenated Blood from the Hepatic Portal vein
The Blood then enter and mix in the Hepatic Sinusoids
As a result, deoxygenated blood then drains from the Hepatic Sinusoids into the Central Vein
Central Veins of each of the Hepatic Lobules then all drain into the Hepatic Vein
Hepatic Vein then drains the deoxygenated blood into the Inferior vena Cava, which drains into the Right Atrium of the heart
Liver
Describe the Cellular Structure of the Liver
The connective tissue of the Liver divides each lobe of the liver into approximately 100 000 Hepatic Lobules
The Structural and Functional Unit of the Liver is the Hepatic Lobule
Each Hepatic Lobule is roughly 1 mm in diameter
The adjacent Hepatic Lobules are separated by an Interlobular Septum formed by the Glisson Capsule
Hepatic Lobule consists of:
Hepatocytes
Hepatocytes in a Liver lobule form a series of irregular plates arranged like the spokes of a wheel
Plates are only one cell thick
Exposed hepatocyte surfaces are covered with short microvilli
Sinusoidal Spaces
Within a lobule, Sinusoids within adjacent plates empty into the Central Vein
Bile Canaliculi
Bile produced in the Liver are transported into the Bile Canaliculi passages
Bile canaliculi passage then drain into the Branch of the Bile Duct
Central Vein
Central vein passes down the core of the Hepatic Lobule
Portal Triad
Portal Triad is made up of three structures:
Branch of the Bile Duct
Branch of the Hepatic Portal vein
Branch of the Hepatic Artery
Lymphatic vessels may also be present within this regions
Describe some of the histological structures seen in the Liver
Stroma
Central vein
Hepatic Lobule
Portal Triad:
Branch of the Hepatic Portal Vein
Vein has a large, irregular lumen and thin walls
Branch of the Proper Hepatic Artery
Artery has a small, regular round lumen
Artery has thicker muscular walls (Tunica media)
Branch of the Bile Duct
4 Lymphatic Vessels
Lymphatic vessel comes up as an empty space
Portal Tract is located at the periphery of the Hepatic Lobules
Portal Space (Tract)
Outline the structures in the Portal Space
Portal Space is located within the hepatic Lobules
Hepatocyte plates are formed by a single row of Hepatocytes that are branched together with multiple nuclei
Branches of Hepatocyte plates leave spaces in between them containing Sinusoids
The multiple Sinusoids of a single Hepatic Lobule then converge(drain) into a single Central Vein
Central vein is located at the core of the Lobule
Border of Hepatocytes that separate the Hepatic Lobule from the Portal Tract are called the Limiting Plate
Injuries to the limiting plate indicate Hepatitis
Bile produced by the hepatocytes gets released into the narrow passages called Bile Canaliculus
Bile canaliculi are located between the opposing surfaces of your hepatocytes
Bile flows from the Canaliculi into the Canal of Hering
From the Canal of Hering, bile crosses the limiting plate and drains into the the Bile duct
Canal of Hering is lined by simple squamous to cuboidal epithelial cells
Canal of Hering have contractility activity which assist in the passage of bile out of the liver into the bile duct
Space of Mall
Space of Mall is located at the Periphery of the Hepatic Lobule
Space of Mall is continuous with the Space of Disse
Space of mall is drained by lymphatic vessels
Space of Disse
Space of Disse separates basolateral domain of hepatocyte from blood circulating in hepatic sinusoids
Space of Disse is a structure that makes sure the blood from the Hepatic Artery and Hepatic Portal Vein do not come into contact with the Hepatocytes
Hepatic Sinusoids
Describe the structure of Hepatic Sinusoids
Hepatic Sinusoids are highly permeable blood capillaries, with a fenestrated, discontinuous Basement Membrane
Large openings between the Endothelial Cells and the Basement Membrane allow for solutes as large as plasma protein to pass out of the bloodstream and into the spaces surrounding the Hepatocytes.
Hepatic Sinusoids have two cell types:
Single layer of Squamous Epithelial Cells
Kupffer Cell
Kupffer cells are called Stellate Reticuloendothelial cells
Kupffer cells are fixed macrophages that sample the blood and engulf pathogens, cell debris, and damaged blood cells
Stellate macrophages also store iron, some lipids, and heavy metals that are absorbed by the GIT
Hepatic Sinusoids receive oxygenated blood from the Hepatic Artery and Nutrient-rich deoxygenated blood from the Hepatic Portal Vein
Hepatic Sinusoids of a single Lobule deliver Deoxygenated Blood to a Central Vein
Bile Canaliculi
Describe the structure of a Bile Canaliculi
Bile Canaliculi is located between two opposed surfaces of adjacent Hepatocytes
Hepatocytes secrete bile into the Bile Canaliculi
Bile flows in the opposite direction to Blood
Bile flows from the Bile Canaliculi into the peripheral Bile Ducts called Canals of Hering and then into the Bile Ducts of the portal space
Bile Ducts then merge to form a Right and Left Hepatic Duct
Right and Left Hepatic Ducts then unite as they exit the Liver to form a Common Hepatic Duct
Common Hepatic Duct then joins the Cystic Duct of the Gallbladder to form the Common Bile Duct
Bile enters the Duodenum of the Small Intestine at the Major Duodenal Papilla
Functional Views of Hepatic Lobule
List the types of Functional Views of Hepatic Lobule
There are three structural-functional organizations of the Hepatocytes, Bile-Duct system and Hepatic Sinusoids
Hepatic Lobule (Classic)
Portal Lobule
Hepatic Acinus (Liver Acinus)
Hepatic Lobule (Classic)
Describe the Hepatic Lobule (Classic)
Classical Hepatic Lobule is an anatomical model which is used to indicate the flow of blood towards the Central Vein
The Classical Hepatic Lobule is Hexagonal in Shape
The Classical Hepatic Lobule is defined as having a Central Vein with Hepatocytes radiating from it in the form of plates
Terminal Branches of the Hepatic Artery, Hepatic Portal Vein and Bile Ductules are located at the angles of the Hepatic Lobule boundary, known as the Portal Triad
Portal Lobule
Outline the Portal Lobule
Portal Lobule is an anatomical model that is used to indicated the flow of Bile towards the Bile Duct of the Portal Triad
Portal Lobule is Triangular in shape
Boundaries of the Portal Lobule are the Central Veins of the three Classical Hepatic Lobules
The centre of the Portal Lobule is the Bile Duct collecting bile from the Bile Canaliculi
It emphasizes the exocrine function, namely Bile secretion, which includes the portions of lobules whose bile canaliculi drain into the same bile duct
Hepatic Acinus
Outline the Hepatic Acinus
Hepatic Acinus is an anatomical model which indicates the flow of arterial blood
Hepatic Acinus is oval in shape
Short axis is between two adjacent Lobules
Long axis is between two adjacent Central Veins
The Boundaries of the Hepatic Acinus are determined by the Terminal Branch of Hepatic Artery
The flow of arterial blood in the Venous Sinusoids creates gradients of Oxygen and Nutrients
As a result, the concentration of oxygen and nutrients in the liver changes as you move from Close to the Portal Tract to the Central Vein
3 Zones are defined by a Metabolic Gradient from the Portal Tract to the Central vein
Zone 1
Zone 1 is called the Peri-Portal Zone
It is the most metabolically active zone
It is the most active regenerative zone
The Oxygen concentration in the Sinusoidal Blood is high
Zone 1 also has a high toxin level
Zone 2
Zone 2 is called the Intermediate Region
There are intermediate levels of Oxygen and Toxins in the blood
Zone 3
Zone 3 is called the Peri-Central Zone
Zone 3 has the poorest Oxygen concentration of blood.
Zone 3 has the lowest toxin levels
It is the most susceptible zone to ischemic damage
Hepatocytes (Hepat=Liver: Cyte=Cell)
Describe the characteristics of the Hepatocytes
Hepatocytes are the Functional Cells of the Liver
Hepatocytes make up 80% of the Volume of the Liver
Hepatocytes are the Function exocrine and endocrine cells of the Hepatic Lobule
Hepatocytes form a 3D complex arrangement called the Hepatic Laminae
Hepatic Laminae contains:
Cuboidal Hepatocyte Cells
Plates of Hepatocytes that are one cell thick
Branch or anastomoses, leaving a space contain venous sinusoids
Hepatocytes
Describe the structure of the Hepatocytes
Hepatocytes have Polarity, meaning that there is a difference in shape, type and size of organelles in the different regions of the cell
Therefore, changes in structure directly relate to changes in function
Hepatocytes have 2 Cellular Domains:
Basolateral Domain
Apical Domain
Apical Membrane borders the Bile Canaliculi
It is lined by microvilli
And it is sealed at its sides by Tight Junctions, to prevent the leakage of Bile from the Bile Canaliculi
Basolateral Membrane
Basolateral Membrane faces the Space of Disse
It has abundant microvilli, to increase the rate and surface area for absorption.
Lateral aspect of the Basolateral membrane is the part between the adjacent Hepatocytes and it contains Adherens and Gap Junctions
Basolateral domain participate sin the absorption of blood-borne substances, secretion of plasma proteins such as Albumin, Fibrinogen, Prothrombin and Coagulation Factors V, VII and IX
Space of Disse
Outline the Space of Disse
Space of Disse is a passage which separates the Basolateral Domain of the Hepatocytes from the blood of the Hepatic Artery and Hepatic Portal Vein circulating in Hepatic Sinusoids.
Space of Disse contains Quiescent Stellate Cells (or Eto or Hepatic Cell) which:
Store Vitamin A in lipid droplets which is then subsequently released as Retinol
Produce extracellular matrix (Collagen Type I)
In response to Liver injury the Quiescent Stellate Cells will become activated and differentiate into Myofibroblasts.
Differentiated Stellate cells secrete Collagen Type I, Glycoproteins and Proteoglycans
Differentiated Stellate cells will also lose the lipid droplets and as result will lose the ability to store Vitamin A.
In the case of Chronic Liver injury, the Stellate Cells will remain differentiated and continue to secrete Collagen Type I to form Extracellular Matrix
As a result, the Liver will become Fibrotic, and lose the function of the Hepatocytes
Reticular fibres such as Type III Collagen and Reticulin form a scaffolding within the Space of Disse
Reticulin fibres are stained black
The scaffolding formed by the Reticular Fibres gives the Lobule integrity
Majority of the Lymph in the body is formed in the Liver
Due to the fenestrations in the Hepatic Sinusoids, tissue fluid and proteins flow freely in the Space of Disse forming Lymph
The Lymph then flows through the Space of Disse and collects in the Lymphatic Capillaries of the Portal Tract
Structure and Function of the Hepatocytes
Describe the cellular structure and function of the Hepatocytes
Hepatocytes have the following cellular structures:
Nucleus
Large, pale Nucleus with abundant euchromatin
This indicates the high transcriptional activity of the Hepatocytes, which further indicates the metabolic activity of the cell.
Numerous Mitochondria
Numerous mitochondria produce ATP
ATP (energy) is required for ATP Transporters in the Apical membrane which transport Bile into the Bile Canaliculi
Mitochondria also play a role in the process of Ammonia Detoxification in Urea cycle
Rough Endoplasmic Reticulum and Golgi Apparatus
Rough ER is responsible for the synthesis of plasma proteins
Golgi Apparatus is responsible for the Glycosylation of secreted Proteins
Peroxisomes
Peroxisomes contain Oxidases and Catalases which are important in the detoxification process of the liver such as breaking down of Alcohol.
Peroxisomes are also responsible for Beta-oxidation of Fatty Acids and the production and breakdown of Hydrogen Peroxide
Zellweger Syndrome is having decreased or non-functioning peroxisomes
Individuals with this syndrome have impaired neuronal migration and brain development
Well developed Smooth Endoplasmic Reticulum
Well developed Smooth ER is responsible for the synthesis of Glycogen, Lipids and Detoxification
Enzymes inserted into the membrane of the Smooth ER are responsible for the:
Synthesis of Cholesterol and Bile Salts
Breakdown of Glycogen into Glucose
Esterification of Fatty Acids to Triglycerides
Abundant Glycogen
Abundant glycogen is used in gluconeogenesis
Lysosomes
Lysosomes store Iron in the form of Ferritin
Lysosomes also degrade aged plasma glycoproteins
Bile Synthesis
Describe the Synthesis of Bile
Hepatocytes produce 600-1200 ml of Bile per day
Bile contains:
Mostly Water
Bile Salts, (Bile acids)
Bilirubin
Glucuronide (Bile pigment)
Phospholipids
Lecithin
Cholesterol
Plasma Electrolytes (especially Sodium, Bicarbonate, and excess Calcium)
IgA
List the Functions of Bile
Bile contributes to Fat Absorption by enterocytes in the Intestinal Lumen
Bile transports IgA to intestinal mucosa
Bile eliminates approximately 80% of Cholesterol synthesized by the Liver
Bile excretes Phospholipids, Conjugated Bilirubin, and Electrolytes
Bile is responsible for the excretion of metabolic products of drugs and heavy metals
Conjugated Bile Acids inhibit bacterial growth
Hepatocyte Exocrine Function
Describe the Exocrine Function of the Hepatocyte
Exocrine Function of the Hepatocyte is Bile production and secretion
The transport of Bile from the Hepatocytes via the Apical membrane to the Bile Canaliculi is an ATP-mediated process
The membrane of the Bile Canaliculi has 4 ATP-dependent Transporters
Each of the 4 ATP-dependent Transporter are responsible for the actively transporting either Cholesterol, Bilirubin, Bile Salts or Phospholipids
The Membrane also has
an Ion Exchanger which exchanges HCO3- ion and Cl- ion into Bile Canaliculi
Hydrolytic ectoenzymes such as Nucleotidase, Peptidase and ATPase
Metabolism of Bilirubin
Explain the Metabolism of Bilirubin
Free Bilirubin is Neurotoxic
In the Spleen, the unconjugated Bilirubin is formed from the breakdown of Heme
In the macrophage Heme is converted to Biliverdin
Biliverdin is in turn is reduced to Bilirubin
Unconjugated Bilirubin is then transported out of the macrophage into the Circulatory System
Excessive amounts of Unconjugated Bilirubin is what can cause excessive destruction of Red Blood Cells and leads to Jaundice
In the Blood, the Albumin binds to Bilirubin, thus causing the Bilirubin to become Water soluble
As a result, the Bilirubin-Albumin complex is too large and it cannot be excreted by Urine
This bilirubin can enter the brain and cause neurological disorders
In the Hepatic Sinusoids, Bilirubin is detached from Albumin
Bilirubin is then transported across the plasma membrane of the hepatocyte and into the Hepatocyte
In the hepatocyte, Bilirubin binds to Ligande, an intracellular Protein Carrier
Forming a Bilirubin-Ligande complex
In the Hepatocyte:
Bilirubin-Ligande complex is chaperoned to Smooth Endoplasmic Reticulum
Free Bilirubin is released from Smooth ER
Glucuronic Acid then attached to Bilirubin, causing it to become Conjugated Bilirubin
In the Bile Ducts, the Conjugated Bilirubin is transported from the hepatocyte to Bile Canaliculi where it is secreted into the Bile
In the Duodenum, Conjugated Bilirubin is converted to Urobilinogen by bacteria
Urobilinogen is excreted
Liver functions
List the differ net functions of the Liver
