Photoreceptor Anatomy and Function

Photoreceptors

• Located in the outer retina and composed of cones and rods
• No rods are found in the fovea
• The periphery of the retina is dominated by rods
• Photoreceptors convert light energy into electrical energy

Photoreceptor Anatomy

• Spherule vs pedicle structure
• Dark current is present when in the dark, maintaining the resting potential of rods
• Depolarized at -40 mV, maintained by Na+/K+ ATPases in the inner segment
• Constant release of the excitatory neurotransmitter glutamate

Rod Activation

• Photons activate the phototransduction cascade
• Closure of the cGMP-Na+ channels
• K+ channels remain open
• Hyperpolarization of the photoreceptor membrane (-70 mV)
• Decrease in glutamate release

Phototransduction Cascade

• Step 1: Light photon activates rhodopsin, converting it to metarhodopsin II
• Step 2: Metarhodopsin II activates transducin, with GDP dissociating and GTP attaching
• Step 3: The alpha-subunit GTP complex binds to both ends of the phosphodiesterase (PDE) molecule, activating PDE
• Step 4: Activated PDE converts cGMP within the outer segment to GMP
• Step 5: Decrease in cGMP within the outer segment, leading to closure of cGMP-dependent channels and subsequent decrease in dark current

Phototransduction Cascade Deactivation

• Guanylate cyclase activating protein is involved in deactivation

Visual Cycle

• ABCR: ATP binding cassette transporter
• atRDH: all-trans retinol dehydrogenase
• IRBP: interphotoreceptor retinoid binding protein
• CRBP: cellular retinol binding protein
• LRAT: lecithin retinol acyl transferase
• RPE65: Retinal pigment epithelium-specific 65 kDa protein
• 11cRDH: 11-cis retinol dehydrogenase

Rods vs Cones

• Visual pigments: rods have rhodopsin, cones have S-cone/M-cone/L-cone (in humans)
• Functional differences: rods are more sensitive to light, rods saturate in moderately bright light – non-functional during daytime, cones remain photosensitive even in bright light, and rods take longer to recover
• Cone alternate recycling of all-trans-retinol

ON/OFF Channels

• ON: depolarize (i.e., turn on) with light onset, hyperpolarize (i.e., turn off) with light offset
• OFF: depolarize with light offset, hyperpolarize with light onset

Mammalian Retina

• The retina consists of several types of cells, including photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells.

Photoreceptors and Synapses

• Photoreceptors (rods and cones) transmit visual signals to bipolar cells through the outer plexiform layer.
• The photoreceptor/bipolar cell synapse is a ribbon synapse.
• Bipolar cells then transmit the signal to ganglion cells through the inner plexiform layer.

Bipolar Cells

• There are two types of bipolar cells: ON bipolar cells and OFF bipolar cells.
• ON bipolar cells have metabotropic glutamate receptor 6 (mGluR6) and are activated in the light and inactivated in the dark.
• OFF bipolar cells have ionotropic glutamate receptor types (AMPA and kainate) and are activated in the dark and inactivated in the light.

Ganglion Cells

• Ganglion cells are divided into ON and OFF types, which receive input from ON and OFF bipolar cells, respectively.
• ON bipolar cells and ON ganglion cells synapse at the inner plexiform layer (IPL) sublamina b.
• OFF bipolar cells and OFF ganglion cells synapse at the IPL sublamina a.
• Rod bipolar cells do not contact ganglion cells.

Ganglion Cell Subtypes

• There are several subtypes of ganglion cells, including:
  • Parasol cells: with larger receptive fields, input to magnocellular layers in the LGN, and detect low contrast and movement.
  • Midget cells: with smaller receptive fields, input to parvocellular layers in the LGN, and are involved in perception of color and fine detail.
  • Bistratified cells: with S cone pathway, proprioception, and IPL sublamina a.
  • Photosensitive cells: projecting to the superior colliculus.

Horizontal Cells

• Horizontal cells are interneurons with dendrites in the outer plexiform layer and cell bodies in the inner nuclear layer.
• They are involved in the lateral pathway.

Mammalian Retina

• The retina consists of several types of cells, including photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells.

Photoreceptors and Synapses

• Photoreceptors (rods and cones) transmit visual signals to bipolar cells through the outer plexiform layer.
• The photoreceptor/bipolar cell synapse is a ribbon synapse.
• Bipolar cells then transmit the signal to ganglion cells through the inner plexiform layer.

Bipolar Cells

• There are two types of bipolar cells: ON bipolar cells and OFF bipolar cells.
• ON bipolar cells have metabotropic glutamate receptor 6 (mGluR6) and are activated in the light and inactivated in the dark.
• OFF bipolar cells have ionotropic glutamate receptor types (AMPA and kainate) and are activated in the dark and inactivated in the light.

Ganglion Cells

• Ganglion cells are divided into ON and OFF types, which receive input from ON and OFF bipolar cells, respectively.
• ON bipolar cells and ON ganglion cells synapse at the inner plexiform layer (IPL) sublamina b.
• OFF bipolar cells and OFF ganglion cells synapse at the IPL sublamina a.
• Rod bipolar cells do not contact ganglion cells.

Ganglion Cell Subtypes

• There are several subtypes of ganglion cells, including:
  • Parasol cells: with larger receptive fields, input to magnocellular layers in the LGN, and detect low contrast and movement.
  • Midget cells: with smaller receptive fields, input to parvocellular layers in the LGN, and are involved in perception of color and fine detail.
  • Bistratified cells: with S cone pathway, proprioception, and IPL sublamina a.
  • Photosensitive cells: projecting to the superior colliculus.

Horizontal Cells

• Horizontal cells are interneurons with dendrites in the outer plexiform layer and cell bodies in the inner nuclear layer.
• They are involved in the lateral pathway.

Objectives and Introduction

• The objectives of the topic include blood overview, heart anatomy, lung anatomy, and cardiopulmonary system and the eye
• Blood is necessary for humans because it transports oxygen and carbon dioxide

Why Blood is Necessary

• Some organisms can oxygenate their cells through diffusion alone, but this requires a moist epithelial surface and low oxygen requirement
• Examples of organisms that use diffusion for oxygenation include jellyfish and sponges
• Some organisms, such as frogs, supplement their circulatory system with diffusion
• In humans, blood is necessary for transporting oxygen and carbon dioxide

What is Blood?

• Blood is a mixture of cellular and acellular fractions that transport nutrients and remove waste products
• The two main components of blood are cells and acellular fractions
• There are two main types of cells in blood: Red Blood Cells and White Blood Cells
• Red Blood Cells make up approximately 45% of blood volume

Blood Vessels

• Arteries receive blood from the heart and need to withstand high pressure, high flow, and high shear.
• Arteries have three tunics: intima, media, and adventitia.
• Intima consists of endothelium monolayer and internal elastic lamina, comprised of connective tissue (elastin).
• Media consists of smooth muscle, elastin, collagen, and external elastic lamina.
• Adventitia consists of connective tissue (collagen and elastin).

Artery Types

• Arteries branch (bifurcate) as they reduce in size.
• Elastic (conduit) arteries have large, very thick walls, elastin to buffer pulse, and collagen for strength (e.g., aorta, ~10mm diameter).
• Distributing (muscular) arteries have reduced medial thickness, contain elastin and collagen, and are involved in blood pressure regulation (e.g., carotid artery, 1-5 mm diameter).
• Arterioles (resistance arteries) have thin media and are involved in setting peripheral resistance (e.g., central retinal artery, ~200 µm).

Capillaries

• Capillaries are the smallest vessels (5-10 µm) with a single endothelial layer surrounded by a basement membrane.
• They are the site of gas and metabolite exchange.
• They represent the anastamosis between arterial and venous circulation.
• Capillaries can be continuous, fenestrated, or sinusoid (levels of leakiness).

Venules

• Venules are the smallest veins (5-15 µm) immediately downstream from capillaries.
• They have intima, very thin media, and adventitia.
• Venules are porous and fragile.
• They merge/coalesce to form veins (e.g., central retinal venule).

Veins

• Veins contain most of the blood in the body.
• They have lower blood pressure than arteries.
• They contain intima, thin media, and adventitia.
• Adventitia thickens with increase in size.
• Valves assist unidirectional blood flow to the heart.

Blood Flow

• In the aorta, blood travels at 30 cm/sec.
• In capillaries, blood travels at 0.3 mm/sec.
• Slowed flow due to overall diameter in all capillaries >> aorta.
• Laminar (smooth) flow is required in the capillary bed.
• Elastin in the arteries dampens pulse waves.

The Arterial Pulse Wave

• The heart pumps from the left ventricle, causing a rise in pressure as the new wave of blood leaves the heart.
• The peak pressure is called the systolic pressure.
• The left heart then begins to fill with blood (returned from the lungs) and pressure drops just before the next pulse (diastole).
• The dicrotic notch represents closure of the aortic valve.

Blood Pressure

• Mean arterial pressure is the average blood pressure in the arterial circulation.
• "Normal" blood pressure is dependent on activity and has a diurnal variation.
• Normal systolic pressure varies depending on the individual.

Blood Vessels

• Arteries receive blood from the heart and need to withstand high pressure, high flow, and high shear.
• Arteries have three tunics: intima, media, and adventitia.
• Intima consists of endothelium monolayer and internal elastic lamina, comprised of connective tissue (elastin).
• Media consists of smooth muscle, elastin, collagen, and external elastic lamina.
• Adventitia consists of connective tissue (collagen and elastin).

Artery Types

• Arteries branch (bifurcate) as they reduce in size.
• Elastic (conduit) arteries have large, very thick walls, elastin to buffer pulse, and collagen for strength (e.g., aorta, ~10mm diameter).
• Distributing (muscular) arteries have reduced medial thickness, contain elastin and collagen, and are involved in blood pressure regulation (e.g., carotid artery, 1-5 mm diameter).
• Arterioles (resistance arteries) have thin media and are involved in setting peripheral resistance (e.g., central retinal artery, ~200 µm).

Capillaries

• Capillaries are the smallest vessels (5-10 µm) with a single endothelial layer surrounded by a basement membrane.
• They are the site of gas and metabolite exchange.
• They represent the anastamosis between arterial and venous circulation.
• Capillaries can be continuous, fenestrated, or sinusoid (levels of leakiness).

Venules

• Venules are the smallest veins (5-15 µm) immediately downstream from capillaries.
• They have intima, very thin media, and adventitia.
• Venules are porous and fragile.
• They merge/coalesce to form veins (e.g., central retinal venule).

Veins

• Veins contain most of the blood in the body.
• They have lower blood pressure than arteries.
• They contain intima, thin media, and adventitia.
• Adventitia thickens with increase in size.
• Valves assist unidirectional blood flow to the heart.

Blood Flow

• In the aorta, blood travels at 30 cm/sec.
• In capillaries, blood travels at 0.3 mm/sec.
• Slowed flow due to overall diameter in all capillaries >> aorta.
• Laminar (smooth) flow is required in the capillary bed.
• Elastin in the arteries dampens pulse waves.

The Arterial Pulse Wave

• The heart pumps from the left ventricle, causing a rise in pressure as the new wave of blood leaves the heart.
• The peak pressure is called the systolic pressure.
• The left heart then begins to fill with blood (returned from the lungs) and pressure drops just before the next pulse (diastole).
• The dicrotic notch represents closure of the aortic valve.

Blood Pressure

• Mean arterial pressure is the average blood pressure in the arterial circulation.
• "Normal" blood pressure is dependent on activity and has a diurnal variation.
• Normal systolic pressure varies depending on the individual.

Lymphatic System Functions

• Fluid homeostasis: lymphatic system returns interstitial fluids back to circulation after fluid flows out of arterioles
• Two types of lymphatic vessels: initial lymphatics and collecting lymphatics
• Initial lymphatics have:
  • Monolayer endothelial cells
  • No continuous basement membrane
  • Discontinuous junctions
  • Endothelial cells considered as primary valve
  • Anchored to extracellular tissue matrix by protein fibrillin
• Collecting lymphatics have:
  • Monolayer endothelial cells
  • Surrounding basement membrane
  • Endothelial cells form continuous, zipper-like tight junctions
  • Contains 1-way valves

Immune System

• Bone marrow:
  • Two components: haematopoietic and vascular
  • Haematopoietic component: haematopoietic stem cells, haematopoietic progenitor cells
  • Vascular component: located in bone marrow stroma, non-haematopoietic progenitor cells differentiating into mesenchymal tissue
  • Provides microenvironment for T cell maturation in absence of thymus
• Immune cells in bone marrow:
  • CD4+ T cells: ~1.5%
  • CD8+ T cells: 2-2.5%
  • Regulatory T cells: ~0.5%
  • CD11c+ dendritic cells: 1-2%
  • B cells: ~1%
  • Plasma cells: ~0.5%
  • Natural killer T cells: 0.4-4%
  • Mesenchymal stem cells: 0.01-0.1%
  • Myeloid-derived suppressor cells: 20-30%
• Thymus: maturation of T cells from bone marrow
• Spleen:
  • Consists of red (~75%) and white (~25%) pulp
  • Red pulp filters old red blood cells, antigens, microorganisms
  • White pulp provides appropriate immune response to blood-borne pathogens
• Tonsils and adenoid: trap pathogens in the nasal and oral passage
• Lymph nodes: ~600 nodes along lymphatic vessels, filter lymph, store and transport B and T cells

Lymphatics in the Eye

• Lymphatic vessels in the eye:
  • Conjunctiva: previously thought to be the only ocular structure with lymphatic vessels
  • Eyelids: classic drainage pathways, but lymphoscintigraphy has cast question on the classical lymphatics system
  • Cornea: Cor LYVE-1 staining
  • Limbus: mice eye, CD31-strong Prox-1- (blood vessels, red); Prox-1+CD31-weak (lymphatics, green)
  • Schlemm's canal: limbal BV, collector channel, Schlemm's canal
  • Ciliary body: red-smooth muscle, blue-blood vessels, green-lymphatic vessels
  • Meninges: flat endothelial cells that lack basal lamina, directly contacting lymph vessel lumen
  • Choroid: general consensus is net-like structures with a "pseudo-vessel" appearance, but evidence for functional lymphatic vessels disputed

Ocular Complications

• Dry eyes: inflammatory disorder, chronic dry eyes can induce lymphangiogenesis in the cornea
• Ocular tumour: lymphoma can be localized or systemic, be aware of new 'bump on the eyelid'

Lymphatic System Functions

• Fluid homeostasis: lymphatic system returns interstitial fluids back to circulation after fluid flows out of arterioles
• Two types of lymphatic vessels: initial lymphatics and collecting lymphatics
• Initial lymphatics have:
  • Monolayer endothelial cells
  • No continuous basement membrane
  • Discontinuous junctions
  • Endothelial cells considered as primary valve
  • Anchored to extracellular tissue matrix by protein fibrillin
• Collecting lymphatics have:
  • Monolayer endothelial cells
  • Surrounding basement membrane
  • Endothelial cells form continuous, zipper-like tight junctions
  • Contains 1-way valves

Immune System

• Bone marrow:
  • Two components: haematopoietic and vascular
  • Haematopoietic component: haematopoietic stem cells, haematopoietic progenitor cells
  • Vascular component: located in bone marrow stroma, non-haematopoietic progenitor cells differentiating into mesenchymal tissue
  • Provides microenvironment for T cell maturation in absence of thymus
• Immune cells in bone marrow:
  • CD4+ T cells: ~1.5%
  • CD8+ T cells: 2-2.5%
  • Regulatory T cells: ~0.5%
  • CD11c+ dendritic cells: 1-2%
  • B cells: ~1%
  • Plasma cells: ~0.5%
  • Natural killer T cells: 0.4-4%
  • Mesenchymal stem cells: 0.01-0.1%
  • Myeloid-derived suppressor cells: 20-30%
• Thymus: maturation of T cells from bone marrow
• Spleen:
  • Consists of red (~75%) and white (~25%) pulp
  • Red pulp filters old red blood cells, antigens, microorganisms
  • White pulp provides appropriate immune response to blood-borne pathogens
• Tonsils and adenoid: trap pathogens in the nasal and oral passage
• Lymph nodes: ~600 nodes along lymphatic vessels, filter lymph, store and transport B and T cells

Lymphatics in the Eye

• Lymphatic vessels in the eye:
  • Conjunctiva: previously thought to be the only ocular structure with lymphatic vessels
  • Eyelids: classic drainage pathways, but lymphoscintigraphy has cast question on the classical lymphatics system
  • Cornea: Cor LYVE-1 staining
  • Limbus: mice eye, CD31-strong Prox-1- (blood vessels, red); Prox-1+CD31-weak (lymphatics, green)
  • Schlemm's canal: limbal BV, collector channel, Schlemm's canal
  • Ciliary body: red-smooth muscle, blue-blood vessels, green-lymphatic vessels
  • Meninges: flat endothelial cells that lack basal lamina, directly contacting lymph vessel lumen
  • Choroid: general consensus is net-like structures with a "pseudo-vessel" appearance, but evidence for functional lymphatic vessels disputed

Ocular Complications

• Dry eyes: inflammatory disorder, chronic dry eyes can induce lymphangiogenesis in the cornea
• Ocular tumour: lymphoma can be localized or systemic, be aware of new 'bump on the eyelid'

Lymphatic System Functions

• Fluid homeostasis: lymphatic system returns interstitial fluids back to circulation after fluid flows out of arterioles
• Two types of lymphatic vessels: initial lymphatics and collecting lymphatics
• Initial lymphatics have:
  • Monolayer endothelial cells
  • No continuous basement membrane
  • Discontinuous junctions
  • Endothelial cells considered as primary valve
  • Anchored to extracellular tissue matrix by protein fibrillin
• Collecting lymphatics have:
  • Monolayer endothelial cells
  • Surrounding basement membrane
  • Endothelial cells form continuous, zipper-like tight junctions
  • Contains 1-way valves

Immune System

• Bone marrow:
  • Two components: haematopoietic and vascular
  • Haematopoietic component: haematopoietic stem cells, haematopoietic progenitor cells
  • Vascular component: located in bone marrow stroma, non-haematopoietic progenitor cells differentiating into mesenchymal tissue
  • Provides microenvironment for T cell maturation in absence of thymus
• Immune cells in bone marrow:
  • CD4+ T cells: ~1.5%
  • CD8+ T cells: 2-2.5%
  • Regulatory T cells: ~0.5%
  • CD11c+ dendritic cells: 1-2%
  • B cells: ~1%
  • Plasma cells: ~0.5%
  • Natural killer T cells: 0.4-4%
  • Mesenchymal stem cells: 0.01-0.1%
  • Myeloid-derived suppressor cells: 20-30%
• Thymus: maturation of T cells from bone marrow
• Spleen:
  • Consists of red (~75%) and white (~25%) pulp
  • Red pulp filters old red blood cells, antigens, microorganisms
  • White pulp provides appropriate immune response to blood-borne pathogens
• Tonsils and adenoid: trap pathogens in the nasal and oral passage
• Lymph nodes: ~600 nodes along lymphatic vessels, filter lymph, store and transport B and T cells

Lymphatics in the Eye

• Lymphatic vessels in the eye:
  • Conjunctiva: previously thought to be the only ocular structure with lymphatic vessels
  • Eyelids: classic drainage pathways, but lymphoscintigraphy has cast question on the classical lymphatics system
  • Cornea: Cor LYVE-1 staining
  • Limbus: mice eye, CD31-strong Prox-1- (blood vessels, red); Prox-1+CD31-weak (lymphatics, green)
  • Schlemm's canal: limbal BV, collector channel, Schlemm's canal
  • Ciliary body: red-smooth muscle, blue-blood vessels, green-lymphatic vessels
  • Meninges: flat endothelial cells that lack basal lamina, directly contacting lymph vessel lumen
  • Choroid: general consensus is net-like structures with a "pseudo-vessel" appearance, but evidence for functional lymphatic vessels disputed

Ocular Complications

• Dry eyes: inflammatory disorder, chronic dry eyes can induce lymphangiogenesis in the cornea
• Ocular tumour: lymphoma can be localized or systemic, be aware of new 'bump on the eyelid'

Kidney Structure

• Kidney is bean-shaped and has three main regions: cortex, medulla, and papilla.
• The nephron is the functional unit of the kidney, consisting of a glomerulus and a renal tubule.

Glomerular Filtration Barrier

• The glomerular filtration barrier has three layers: endothelium, basement membrane, and epithelium.
• Endothelium has pores 70-100 nm in diameter, allowing fluid and dissolved solutes to pass through.
• Basement membrane is formed by the membranes of the endothelium and epithelium.
• Epithelium has podocytes with foot processes, forming filtration slits 25-60 nm in diameter.

Glomerular Filtration Barrier Function

• The glomerular filtration barrier prevents large molecules (e.g. proteins and cells) from passing through due to physical and electrostatic barriers.
• Negatively charged glycoproteins in the barrier repel negatively charged proteins.

Kidney Function

• The kidney's most important function is the reabsorption of sodium, which determines extracellular fluid volume.
• The kidney also regulates electrolyte and water homeostasis, blood pH, and waste clearance.
• It produces hormones including renin, erythropoietin, and vitamin D.

Diabetes

• Diabetes is a condition where insulin production or sensitivity is affected, leading to increased blood sugar levels.
• There are three types of diabetes: Type I, Type II, and Gestational.

Diabetic Retinopathy

• Diabetic retinopathy is a condition where high blood sugar levels damage blood vessels in the eyes.

Liver Structure

• The liver is the largest solid organ, weighing 1.5 kg in adults.
• It receives 75% of its blood flow from the portal vein and 25% from the hepatic artery.
• The functional unit of the liver is the liver lobule, which is cylindrical in shape and 0.8-2 mm in diameter.

Liver Cell Types

• Hepatocytes make up 80% of liver cells and perform basic liver functions, such as storing glycogen and vitamins, and metabolizing lipids and drugs.
• Hepatic stellate cells make up 5% of liver cells and store vitamin A and lipids.
• Kupffer cells are immune sentinels, and liver sinusoidal endothelial cells form a permeable barrier between blood cells and hepatocytes.

Liver Function

• The liver performs various functions, including glucose metabolism, lipid and cholesterol metabolism, protein synthesis, and haeme synthesis.
• It also produces bile, which aids lipid absorption and bilirubin excretion.
• The liver is responsible for red blood cell turnover and bilirubin storage.

Liver Function (continued)

• The liver metabolizes drugs in two phases: Phase 1 involves oxidation or hydroxylation, and Phase 2 involves conjugation.

Jaundice

• Jaundice is a condition where bilirubin builds up, causing yellow skin and conjunctiva.
• It is common in newborns and can be caused by liver damage, bile flow interference, or excess bilirubin production in adults.
• Treatment depends on the underlying cause.

Kidney Structure

• Kidney is bean-shaped and has three main regions: cortex, medulla, and papilla.
• The nephron is the functional unit of the kidney, consisting of a glomerulus and a renal tubule.

Glomerular Filtration Barrier

• The glomerular filtration barrier has three layers: endothelium, basement membrane, and epithelium.
• Endothelium has pores 70-100 nm in diameter, allowing fluid and dissolved solutes to pass through.
• Basement membrane is formed by the membranes of the endothelium and epithelium.
• Epithelium has podocytes with foot processes, forming filtration slits 25-60 nm in diameter.

Glomerular Filtration Barrier Function

• The glomerular filtration barrier prevents large molecules (e.g. proteins and cells) from passing through due to physical and electrostatic barriers.
• Negatively charged glycoproteins in the barrier repel negatively charged proteins.

Kidney Function

• The kidney's most important function is the reabsorption of sodium, which determines extracellular fluid volume.
• The kidney also regulates electrolyte and water homeostasis, blood pH, and waste clearance.
• It produces hormones including renin, erythropoietin, and vitamin D.

Diabetes

• Diabetes is a condition where insulin production or sensitivity is affected, leading to increased blood sugar levels.
• There are three types of diabetes: Type I, Type II, and Gestational.

Diabetic Retinopathy

• Diabetic retinopathy is a condition where high blood sugar levels damage blood vessels in the eyes.

Liver Structure

• The liver is the largest solid organ, weighing 1.5 kg in adults.
• It receives 75% of its blood flow from the portal vein and 25% from the hepatic artery.
• The functional unit of the liver is the liver lobule, which is cylindrical in shape and 0.8-2 mm in diameter.

Liver Cell Types

• Hepatocytes make up 80% of liver cells and perform basic liver functions, such as storing glycogen and vitamins, and metabolizing lipids and drugs.
• Hepatic stellate cells make up 5% of liver cells and store vitamin A and lipids.
• Kupffer cells are immune sentinels, and liver sinusoidal endothelial cells form a permeable barrier between blood cells and hepatocytes.

Liver Function

• The liver performs various functions, including glucose metabolism, lipid and cholesterol metabolism, protein synthesis, and haeme synthesis.
• It also produces bile, which aids lipid absorption and bilirubin excretion.
• The liver is responsible for red blood cell turnover and bilirubin storage.

Liver Function (continued)

• The liver metabolizes drugs in two phases: Phase 1 involves oxidation or hydroxylation, and Phase 2 involves conjugation.

Jaundice

• Jaundice is a condition where bilirubin builds up, causing yellow skin and conjunctiva.
• It is common in newborns and can be caused by liver damage, bile flow interference, or excess bilirubin production in adults.
• Treatment depends on the underlying cause.

ATP and Energy Production

• ATP (Adenosine Triphosphate) is the main energy unit in the body, with the human body using its body weight of ATP daily.
• The average lifespan of an ATP molecule is 1-5 minutes, and it can be recycled around 300 times a day.
• ATP is generated from the breakdown of glucose, proteins, and lipids.
• The citric acid (Krebs) cycle is involved in ATP production.

Glucose Homeostasis

• Glucose levels are regulated by hormones, including insulin (decreases blood glucose levels) and glucagon (increases blood glucose levels).
• Organs involved in glucose homeostasis include the pancreas, liver, and muscles.

Pancreas Functions

• The pancreas has exocrine (acinar) tissue, which produces enzymes for food digestion, and endocrine (islets) tissue, which produces hormones like insulin and glucagon.
• Islets in the pancreas produce hormones, including insulin and glucagon.

Insulin and Glucagon Secretion

• Insulin secretion is stimulated by high glucose levels, which increases intracellular ATP, closing β-cell KATP channels, and leading to insulin exocytosis.
• Glucagon secretion is stimulated by low glucose levels, which decreases intracellular ATP, opening KATP channels, and leading to glucagon exocytosis.

Diabetes Mellitus

• Diabetes mellitus is characterized by hyperglycaemia (high blood glucose levels).
• There are three types of diabetes mellitus: Type 1 (juvenile/insulin-dependent), Type 2 (mature/non-insulin-dependent), and Gestational diabetes.

Type 1 Diabetes Mellitus

• Type 1 DM is caused by the destruction of β-cells, resulting in no insulin production.
• It is an autoimmune disease with a low incidence (~1/400).
• Treatment options include insulin injection, pancreas transplant, and islet transplant.

Type 2 Diabetes Mellitus

• Type 2 DM is associated with obesity, which increases insulin resistance.
• It has a high incidence and is characterized by two main pathophysiological mechanisms: insulin resistance and reduced insulin secretion.
• Complications of Type 2 DM include acute and chronic complications, such as nonketotic hyperosmolar coma.

ATP and Energy Production

• ATP (Adenosine Triphosphate) is the main energy unit in the body, with the human body using its body weight of ATP daily.
• The average lifespan of an ATP molecule is 1-5 minutes, and it can be recycled around 300 times a day.
• ATP is generated from the breakdown of glucose, proteins, and lipids.
• The citric acid (Krebs) cycle is involved in ATP production.

Glucose Homeostasis

• Glucose levels are regulated by hormones, including insulin (decreases blood glucose levels) and glucagon (increases blood glucose levels).
• Organs involved in glucose homeostasis include the pancreas, liver, and muscles.

Pancreas Functions

• The pancreas has exocrine (acinar) tissue, which produces enzymes for food digestion, and endocrine (islets) tissue, which produces hormones like insulin and glucagon.
• Islets in the pancreas produce hormones, including insulin and glucagon.

Insulin and Glucagon Secretion

• Insulin secretion is stimulated by high glucose levels, which increases intracellular ATP, closing β-cell KATP channels, and leading to insulin exocytosis.
• Glucagon secretion is stimulated by low glucose levels, which decreases intracellular ATP, opening KATP channels, and leading to glucagon exocytosis.

Diabetes Mellitus

• Diabetes mellitus is characterized by hyperglycaemia (high blood glucose levels).
• There are three types of diabetes mellitus: Type 1 (juvenile/insulin-dependent), Type 2 (mature/non-insulin-dependent), and Gestational diabetes.

Type 1 Diabetes Mellitus

• Type 1 DM is caused by the destruction of β-cells, resulting in no insulin production.
• It is an autoimmune disease with a low incidence (~1/400).
• Treatment options include insulin injection, pancreas transplant, and islet transplant.

Type 2 Diabetes Mellitus

• Type 2 DM is associated with obesity, which increases insulin resistance.
• It has a high incidence and is characterized by two main pathophysiological mechanisms: insulin resistance and reduced insulin secretion.
• Complications of Type 2 DM include acute and chronic complications, such as nonketotic hyperosmolar coma.

Muscle Cells

• Specialized cells that contract, responsible for body movement and controlling shape/size of internal organs
• Elongated shape, arranged in parallel array

Muscle Types

• 2 classes: striated and smooth
• Striated muscles:
  • Exhibit cross striation, arranged in bundles
  • 2 subtypes: skeletal (attached to bone) and cardiac (heart muscle)
• Smooth muscles:
  • No cross striation, arranged in sheets
  • Found in internal organs (except heart)

Skeletal Muscle

• Elongated muscle cells embedded in connective tissue framework
• Comprises collagen fibers, fibroblasts, neurovascular bundles
• 40% of body weight, responsible for movement of limbs and digits, maintenance of body posture

Skeletal Muscle Fibers

• Categorized by diameter and natural color:
  • Red fibers: small, with large amounts of myoglobin, cytochromes, and mitochondria (slow twitch)
  • White fibers: large, with less myoglobin, fewer cytochromes and mitochondria (fast twitch)
  • Intermediate fibers: intermediate in size, with myoglobin, cytochromes, and mitochondrial numbers between red and white fibers

Cardiac Muscle

• Heart muscle, striated
• Differ from other muscle types:
  • Inherent rhythmicity, spontaneous contraction via sinus node in right atrium
  • Cellular membrane of myocytes intertwined, form intercalated discs – synchronized contraction

Smooth Muscle

• No striation
• Not under voluntary control, regulated by autonomic nervous system
• Organized as single unit (visceral) or multiunit
  • Visceral: muscle fibers joined by gap junction, contracts as single unit
  • Multiunit (e.g. iris): no gap junction, independent contraction

Neurons

• Classified morphologically
• Information passes from dendrite to axonal terminal
• Myelin sheath allows faster electrical impulse transmission

Neuron Functional Types

• Sensory neurons (afferent): receive sensory input at dendritic terminals, information moves towards CNS
• Motor neurons (efferent): send impulses to muscles, glands, other neurons, information moves away from CNS
• Interneurons: located within CNS, establish networks between sensory and motor neurons

Synapse

• Neurotransmitters have specific receptors, excitatory or inhibitory, promote or prevent action potential
• Common neurotransmitters: biogenic amines, amino acids, nucleotides, gases, neuropeptides

Glial Cells

• Non-neuronal, support cells in CNS and PNS
• CNS: astrocytes, oligodendrocytes, ependymal cells, microglia
• PNS: Schwann cells, satellite cells
• Functions:
  • Astrocytes: maintain blood-brain barrier (BBB) and extracellular homeostasis
  • Oligodendrocytes: myelinate axons
  • Ependymal cells: produce cerebrospinal fluid
  • Microglia: macrophage, clear cell debris and dead neurons
  • Schwann cells: myelinate PNS axons
  • Satellite cells: maintain extracellular homeostasis

Epithelial Tissue

• Avascular, composed of specialized junctions, apical surface, and basement membrane
• Two types: surface epithelium and glandular epithelium
• Origins: surface epithelium from ectoderm, mesoderm, and endoderm; glandular epithelium from ectoderm, mesoderm, and endoderm
• Functions: protection, secretion, transcellular transport, and absorption
• Polarity: most epithelial cells have a top (apical) and bottom (basal) surface

Classification of Epithelia

• Classified by number of cell layers and shape of cells in the surface layer
• Simple epithelia: one cell layer thick, squamous, cuboidal, or columnar
• Stratified epithelia: two or more cell layers, classified by the shape of cells in the surface layer

Simple Epithelia

• Found in interfaces for selective diffusion, absorption, and/or secretion
• Squamous: found in endothelial lining of blood vessels and mesothelial lining of body cavities
• Cuboidal: function in secretion/absorption, found in collecting tubules of the kidney, ducts draining exocrine glands, and under the anterior lens capsule
• Columnar: function in secretion/absorption/protection, found in the internal surface of the GI tract
• Pseudostratified: appears as if cells are not in contact with the basal lamina, found in the upper respiratory tract and vas deferens

Stratified Epithelia

• Mostly involved in providing protection
• Classified based on the most superficial cells
• Squamous: outer layer squamous cell, function in protection to mechanical stress and desiccation, keratinized or non-keratinized
• Columnar: inner layers can be other epithelial cell types, cells in apical layer connected by gap junctions and desmosomes, functions in protection/secretion
• Cuboidal: inner layers can be other epithelial cell types, cells in apical layer connected by gap junctions and desmosomes, main function: secretion
• Transitional/Transitional epithelium: cells can change shape depending on tissue distention, found in the epithelial lining of the lower urinary tract (urothelium)

Glandular Epithelium

• Simplest form: invagination of the surface epithelium
• Two groups: exocrine and endocrine
• Exocrine glands: release content onto an epithelial surface directly or via a duct, classified according to the nature of their secretion, mode of secretion, and number of cells
• Endocrine glands: release into the bloodstream, do not have ducts, major endocrine glands of the body include pituitary, adrenal, thyroid, parathyroid, pineal, and pancreas

Connective Tissue (CT)

• Provides support: general scaffolding, tensile strength, elasticity, and space filling
• Consists of cells surrounded by extracellular matrix (ECM)
• 3 classes: loose, dense, and specialized
• Loose CT: most common type, loosely packed fibers separated by large amount of ground substance, provides mechanical strength with physical and metabolic support
• Dense CT: high proportion of fibers, little ground substance, 2 subtypes: regular and irregular
• Regular dense CT: collagen bundles arranged in one general direction, maximal tensile strength, found in tendons and corneal stroma
• Irregular dense CT: collagen bundles oriented in various 3D arrays, enables tissue to withstand tension from different directions, found in dermis and sclera

Basement Membrane (BM)

• Specialized collection of connective tissue fibers and matrix located subjacent to the basal portion of epithelial cells
• Found between cell and underlying CT, also around endothelium, muscle cells, fat, and peripheral nerve cells
• 3 layers: lamina lucida, lamina densa, and lamina fibroreticularis/reticular lamina
• Functions: physically binds the epithelium to the underlying tissue, controls epithelial growth and differentiation, regulates permeability
• Components: type IV collagen, laminin, nidogen/entactin, fibronectin, glycoproteins, and proteoglycans

Epithelial Tissue

• Avascular, composed of specialized junctions, apical surface, and basement membrane
• Two types: surface epithelium and glandular epithelium
• Origins: surface epithelium from ectoderm, mesoderm, and endoderm; glandular epithelium from ectoderm, mesoderm, and endoderm
• Functions: protection, secretion, transcellular transport, and absorption
• Polarity: most epithelial cells have a top (apical) and bottom (basal) surface

Classification of Epithelia

• Classified by number of cell layers and shape of cells in the surface layer
• Simple epithelia: one cell layer thick, squamous, cuboidal, or columnar
• Stratified epithelia: two or more cell layers, classified by the shape of cells in the surface layer

Simple Epithelia

• Found in interfaces for selective diffusion, absorption, and/or secretion
• Squamous: found in endothelial lining of blood vessels and mesothelial lining of body cavities
• Cuboidal: function in secretion/absorption, found in collecting tubules of the kidney, ducts draining exocrine glands, and under the anterior lens capsule
• Columnar: function in secretion/absorption/protection, found in the internal surface of the GI tract
• Pseudostratified: appears as if cells are not in contact with the basal lamina, found in the upper respiratory tract and vas deferens

Stratified Epithelia

• Mostly involved in providing protection
• Classified based on the most superficial cells
• Squamous: outer layer squamous cell, function in protection to mechanical stress and desiccation, keratinized or non-keratinized
• Columnar: inner layers can be other epithelial cell types, cells in apical layer connected by gap junctions and desmosomes, functions in protection/secretion
• Cuboidal: inner layers can be other epithelial cell types, cells in apical layer connected by gap junctions and desmosomes, main function: secretion
• Transitional/Transitional epithelium: cells can change shape depending on tissue distention, found in the epithelial lining of the lower urinary tract (urothelium)

Glandular Epithelium

• Simplest form: invagination of the surface epithelium
• Two groups: exocrine and endocrine
• Exocrine glands: release content onto an epithelial surface directly or via a duct, classified according to the nature of their secretion, mode of secretion, and number of cells
• Endocrine glands: release into the bloodstream, do not have ducts, major endocrine glands of the body include pituitary, adrenal, thyroid, parathyroid, pineal, and pancreas

Connective Tissue (CT)

• Provides support: general scaffolding, tensile strength, elasticity, and space filling
• Consists of cells surrounded by extracellular matrix (ECM)
• 3 classes: loose, dense, and specialized
• Loose CT: most common type, loosely packed fibers separated by large amount of ground substance, provides mechanical strength with physical and metabolic support
• Dense CT: high proportion of fibers, little ground substance, 2 subtypes: regular and irregular
• Regular dense CT: collagen bundles arranged in one general direction, maximal tensile strength, found in tendons and corneal stroma
• Irregular dense CT: collagen bundles oriented in various 3D arrays, enables tissue to withstand tension from different directions, found in dermis and sclera

Basement Membrane (BM)

• Specialized collection of connective tissue fibers and matrix located subjacent to the basal portion of epithelial cells
• Found between cell and underlying CT, also around endothelium, muscle cells, fat, and peripheral nerve cells
• 3 layers: lamina lucida, lamina densa, and lamina fibroreticularis/reticular lamina
• Functions: physically binds the epithelium to the underlying tissue, controls epithelial growth and differentiation, regulates permeability
• Components: type IV collagen, laminin, nidogen/entactin, fibronectin, glycoproteins, and proteoglycans

Embryonic Development

• 4 stages of embryonic development:
• Fertilisation: sperm + egg forms a zygote
• Cleavage: multiple rounds of mitotic cell division, resulting in a blastula
• Gastrulation: rearrangement of cells to form embryonic tissue layers
• Organogenesis: organ and tissue formation
• At 5 days post-fertilisation, the embryo consists of an internal cell mass (forms the embryo) and trophoblasts/outer layer cells (forms the placenta)

Embryogenesis

• Occurs between 2-8 weeks post-fertilisation
• Inner cell mass differentiates into the embryo
• Bilaminar disc forms within the amniotic cavity, giving the embryo its first orientation (dorsal/epiblast and ventral/hypoblast axis)
• Gastrulation: proliferation and migration of epiblast into 3 germ layers, resulting in a trilaminar mass of cells (gastrula)

Germ Layers

• Ectoderm:
• Differentiates into 2 parts: surface ectoderm and neural tube
• Formations: retina, epithelial linings of iris and ciliary body, optic nerve, lens, corneal and conjunctival epithelium, eyelids
• Mesoderm:
• Formations: sclera, choroid, corneal stroma, vitreous, extraocular muscles
• Endoderm:
• Folds to form the subdivisions of the primitive gut (foregut, midgut, hindgut)
• Formations: pharynx, lower respiratory tract, esophagus, stomach, duodenum, liver, pancreas, small intestine, large intestine

Eye Development

• Week 4:
• Bilateral indentations form (optical grooves/sulci) on each side of the forebrain
• Optic vesicles develop and interact with surface ectoderm
• Lens placode forms, inducing the optic vesicle to thicken and form the retinal disc
• Week 5:
• Invagination of the optic vesicle forms the optic cup
• Development of the lens placode triggers invagination of the optic vesicle
• Optic fissure begins to close
• Week 6:
• Invaginating lens placode forms the lens vesicle
• The hyaloid artery wraps around the posterior lens
• Optic fissure closure continues
• Week 7:
• Retina develops from the dorsal neuroectoderm of the optic vesicle
• RPE (retinal pigment epithelium) forms a single layer of cuboidal cells
• Bruch's membrane (primitive) arises
• Sensory retina thickens
• Week 8:
• RPE matures
• Sensory retina: outer and inner neuroblastic layers develop
• Primary lens fibers form, obliterating the cavity within the lens vesicle
• Periocular mesenchyme: formation of choroidal vasculature, corneal stroma, endothelium, trabecular meshwork, and Schlemm's canal

Critical Period of Eye Development

• Week 4 to 8: critical period of eye development
• Vision is fine-tuned via visual input after birth

Embryonic Development

• 4 stages of embryonic development:
• Fertilisation: sperm + egg forms a zygote
• Cleavage: multiple rounds of mitotic cell division, resulting in a blastula
• Gastrulation: rearrangement of cells to form embryonic tissue layers
• Organogenesis: organ and tissue formation
• At 5 days post-fertilisation, the embryo consists of an internal cell mass (forms the embryo) and trophoblasts/outer layer cells (forms the placenta)

Embryogenesis

• Occurs between 2-8 weeks post-fertilisation
• Inner cell mass differentiates into the embryo
• Bilaminar disc forms within the amniotic cavity, giving the embryo its first orientation (dorsal/epiblast and ventral/hypoblast axis)
• Gastrulation: proliferation and migration of epiblast into 3 germ layers, resulting in a trilaminar mass of cells (gastrula)

Germ Layers

• Ectoderm:
• Differentiates into 2 parts: surface ectoderm and neural tube
• Formations: retina, epithelial linings of iris and ciliary body, optic nerve, lens, corneal and conjunctival epithelium, eyelids
• Mesoderm:
• Formations: sclera, choroid, corneal stroma, vitreous, extraocular muscles
• Endoderm:
• Folds to form the subdivisions of the primitive gut (foregut, midgut, hindgut)
• Formations: pharynx, lower respiratory tract, esophagus, stomach, duodenum, liver, pancreas, small intestine, large intestine

Eye Development

• Week 4:
• Bilateral indentations form (optical grooves/sulci) on each side of the forebrain
• Optic vesicles develop and interact with surface ectoderm
• Lens placode forms, inducing the optic vesicle to thicken and form the retinal disc
• Week 5:
• Invagination of the optic vesicle forms the optic cup
• Development of the lens placode triggers invagination of the optic vesicle
• Optic fissure begins to close
• Week 6:
• Invaginating lens placode forms the lens vesicle
• The hyaloid artery wraps around the posterior lens
• Optic fissure closure continues
• Week 7:
• Retina develops from the dorsal neuroectoderm of the optic vesicle
• RPE (retinal pigment epithelium) forms a single layer of cuboidal cells
• Bruch's membrane (primitive) arises
• Sensory retina thickens
• Week 8:
• RPE matures
• Sensory retina: outer and inner neuroblastic layers develop
• Primary lens fibers form, obliterating the cavity within the lens vesicle
• Periocular mesenchyme: formation of choroidal vasculature, corneal stroma, endothelium, trabecular meshwork, and Schlemm's canal

Critical Period of Eye Development

• Week 4 to 8: critical period of eye development
• Vision is fine-tuned via visual input after birth

Anatomy of the Skull and Orbit

• The skull consists of 22 bones united at immobile joints called sutures.
• The 22 bones are divided into:
  • Cranium (8 bones): protects the brain
  • Facial bones (14 bones): "hang" off the cranium
• Cranial bones:
  • Frontal bone x 1
  • Parietal bones x 2
  • Occipital bone x 1
  • Temporal bones x 2
  • Sphenoid bone x 1
  • Ethmoid bone x 1
• Facial bones:
  • Zygomatic bones x 2
  • Maxillary bones x 2
  • Nasal bones x 2
  • Lacrimal bones x 2
  • Vomer x 1
  • Palatine bones x 2
  • Inferior conchae x 2
  • Mandible x 1

The Orbit

• The orbit is a pyramidal/conical shaped cavity with dimensions of approximately 40mm x 40mm x 40mm.
• The eye occupies about 1/5 of the orbit, while the remaining 4/5 is occupied by:
  • Optic nerve
  • Extraocular muscles
  • Lacrimal gland
  • Nerves
  • Connective tissue (orbital fat)

Orbital Bones

• The 7 bones that make up the orbit are:
  • Maxillary bone
  • Zygomatic bone
  • Lacrimal bone
  • Ethmoid bone
  • Palatine bone
  • Sphenoid bone
  • Frontal bone
• These bones are designed to protect the globe.

Orbital Margin

• Supraorbital margin:
  • Formed by the frontal bone
  • Note supraorbital notch (open) or foramen (closed)
  • Allows passage of the supraorbital neurovascular bundle
• Infraorbital margin:
  • Formed by the zygomatic bone (laterally) and maxillary bone (medially)
• Lateral margin:
  • Formed by the zygomatic process of the frontal bone and frontal process of the zygomatic bone
• Medial margin:
  • Formed by the maxillary process of the frontal bone and frontal process of the maxillary bone

Walls of the Orbit

• Roof:
  • Composed of 2 bones: frontal bone and lesser wing of sphenoid
  • Contains optic canal
• Floor:
  • Composed of 3 bones: maxillary bone, zygomatic bone, and palatine bone
  • Very thin, most susceptible to fracture
• Medial wall:
  • Composed of 5 bones: ethmoid bone, lacrimal bone, body of sphenoid bone, frontal bone, and maxillary bone
  • Thin wall
• Lateral wall:
  • Composed of 2 bones: greater wing of sphenoid and zygomatic bone
  • Thickest wall for protection

Orbital Fracture

• Two theories: hydraulic and buckling
• History of blunt trauma
• Floor most susceptible to fracture, followed by medial wall
• Symptoms: bruising, tenderness, redness, double vision
• CT scans needed for diagnosis

Openings into the Orbital Cavity

• Optic canal:
  • Within the lesser wing of the sphenoid
  • Transmits the optic nerve and ophthalmic artery
• Superior orbital fissure:
  • Between the lesser and greater wings of the sphenoid
  • Transmits most of the other vascular and neural structures into the orbit
• Inferior orbital fissure:
  • Between the greater wing of sphenoid and maxillary bone
  • Mainly transmits inferior ophthalmic vein and maxillary division of the trigeminal nerve
• Foramina:
  • Anterior and posterior ethmoid
  • Transmit ethmoidal nerves and arteries

Nasal Cavity and Tear Drainage

• Nasal cavity:
  • Internal component of the nose
  • Contains 4 sinuses
  • Sinus functions:
    • Support immune defense
    • Humidify inspired air
    • Voice resonance
    • Lighten skull
• Tear drainage:
  • Punctum → lacrimal canaliculi → lacrimal sac → nasolacrimal duct → nasal cavity
  • Ducts may be blocked, lacrimal lavage to clear the blockage

Anatomy of the Skull and Orbit

• The skull consists of 22 bones united at immobile joints called sutures.
• The 22 bones are divided into:
  • Cranium (8 bones): protects the brain
  • Facial bones (14 bones): "hang" off the cranium
• Cranial bones:
  • Frontal bone x 1
  • Parietal bones x 2
  • Occipital bone x 1
  • Temporal bones x 2
  • Sphenoid bone x 1
  • Ethmoid bone x 1
• Facial bones:
  • Zygomatic bones x 2
  • Maxillary bones x 2
  • Nasal bones x 2
  • Lacrimal bones x 2
  • Vomer x 1
  • Palatine bones x 2
  • Inferior conchae x 2
  • Mandible x 1

The Orbit

• The orbit is a pyramidal/conical shaped cavity with dimensions of approximately 40mm x 40mm x 40mm.
• The eye occupies about 1/5 of the orbit, while the remaining 4/5 is occupied by:
  • Optic nerve
  • Extraocular muscles
  • Lacrimal gland
  • Nerves
  • Connective tissue (orbital fat)

Orbital Bones

• The 7 bones that make up the orbit are:
  • Maxillary bone
  • Zygomatic bone
  • Lacrimal bone
  • Ethmoid bone
  • Palatine bone
  • Sphenoid bone
  • Frontal bone
• These bones are designed to protect the globe.

Orbital Margin

• Supraorbital margin:
  • Formed by the frontal bone
  • Note supraorbital notch (open) or foramen (closed)
  • Allows passage of the supraorbital neurovascular bundle
• Infraorbital margin:
  • Formed by the zygomatic bone (laterally) and maxillary bone (medially)
• Lateral margin:
  • Formed by the zygomatic process of the frontal bone and frontal process of the zygomatic bone
• Medial margin:
  • Formed by the maxillary process of the frontal bone and frontal process of the maxillary bone

Walls of the Orbit

• Roof:
  • Composed of 2 bones: frontal bone and lesser wing of sphenoid
  • Contains optic canal
• Floor:
  • Composed of 3 bones: maxillary bone, zygomatic bone, and palatine bone
  • Very thin, most susceptible to fracture
• Medial wall:
  • Composed of 5 bones: ethmoid bone, lacrimal bone, body of sphenoid bone, frontal bone, and maxillary bone
  • Thin wall
• Lateral wall:
  • Composed of 2 bones: greater wing of sphenoid and zygomatic bone
  • Thickest wall for protection

Orbital Fracture

• Two theories: hydraulic and buckling
• History of blunt trauma
• Floor most susceptible to fracture, followed by medial wall
• Symptoms: bruising, tenderness, redness, double vision
• CT scans needed for diagnosis

Openings into the Orbital Cavity

• Optic canal:
  • Within the lesser wing of the sphenoid
  • Transmits the optic nerve and ophthalmic artery
• Superior orbital fissure:
  • Between the lesser and greater wings of the sphenoid
  • Transmits most of the other vascular and neural structures into the orbit
• Inferior orbital fissure:
  • Between the greater wing of sphenoid and maxillary bone
  • Mainly transmits inferior ophthalmic vein and maxillary division of the trigeminal nerve
• Foramina:
  • Anterior and posterior ethmoid
  • Transmit ethmoidal nerves and arteries

Nasal Cavity and Tear Drainage

• Nasal cavity:
  • Internal component of the nose
  • Contains 4 sinuses
  • Sinus functions:
    • Support immune defense
    • Humidify inspired air
    • Voice resonance
    • Lighten skull
• Tear drainage:
  • Punctum → lacrimal canaliculi → lacrimal sac → nasolacrimal duct → nasal cavity
  • Ducts may be blocked, lacrimal lavage to clear the blockage

Sclera

• Whish outer coat of the eye
• Derived from Greek "skleros" meaning hard
• Dense, irregular connective tissue (CT)

Functions of Sclera

• Protection: tough barrier separating intraocular structures from orbital walls and the outside world
• Refractive stability: keeps eye length stable during changes in intraocular pressure and blood pressure, and during eye movements and accommodation
• Conduit for nerves and vessels: allows nerve and vessel access to underlying ocular structures
• Anchor for extraocular muscles: provides stable anchorage for extraocular muscle tendons, contributing to stability of torsional movements
• Anchor for ciliary muscle: opposes contractile forces of ciliary muscle, allowing stable accommodation
• Facilitates ocular drainage: majority of aqueous outflow through intrascleral venous plexus to the episcleral plexus

Openings in the Sclera

• Minor foramina: allow blood vessels and nerves to pierce the eyeball
• Two major foramina: anterior scleral foramen (cornea) and posterior scleral foramen (scleral canal)

Layers of the Sclera

• Episclera: outermost layer, merges with the underlying scleral stroma
• Scleral stroma: dense, irregular CT
• Lamina fusca: innermost layer, regarded as part of choroid by some, but separated from choroid by perichoroidal space

Biochemical Composition of the Sclera

• Collagen (around 90% of scleral dry weight, predominantly type I)
• Proteoglycans and glycosaminoglycans (around 1% of dry weight)
• Glycoproteins (e.g. fibronectin)
• Fibroblasts, myofibroblasts, and some melanocytes
• Non-collagenous proteins (e.g. elastin, proteases, etc.)
• Water

Scleral Cells

• Fibroblasts: synthesise collagen, elastic, and reticular fibres, reside close to collagen matrices
• Myofibroblasts: modified fibroblasts, synthesise collagen, express contractile proteins (e.g. α-smooth muscle actin), present in mammals, including humans

Scleral Collagens

• Structural unit: tropocollagen/collagen (~3 intertwined polypeptide chains, rich in amino acids proline and hydroxyproline)
• Staggered collagen molecules assemble into a fibril

Scleral Proteoglycans

• ~0.7-0.9% of the total scleral dry weight
• Modulate collagen fibril assembly and arrangement
• Aggrecan, biglycan, and decorin: sequester water within the scleral ECM, highest concentration in the posterior sclera, possibly maintaining posterior pole flexibility