Bone , Cartilage & Ossification ( The Histology Guide )

 Bones & Cartilage

Bones

•  Bone is a specialized connective tissue composed of calcified intercellular material,  bone,matrix, and three cell types. 

•  Is a specialized connective tissue. 

•  Highly vascular.

•  Hard, rigid, somewhat resilient 

•  Constantly changing. 

•  Have regenerating capacity (Cartilage doesn’t have) 

•  Characteristic growth mechanism – apposition only 

•  Canalicular system for transportation of nutrients.  

•  In adults, red marrow is limited to the spongy bone in the skull, ribs, sternum, clavicles, vertebrae & pelvis.

Functions of bones

Support - Provide rigid framework for the entire body

Movement - Muscles attach by tendons and use bones as levers to move

Protection -   Skull : brain  ,  Vertebrae : Spinal cord  ,  Rib cage : Thoracic organs

Mineral storage - Calcium and phosphorus , Released as ions into blood as needed

Blood cell formation and energy storage - bone marrow : Red makes blood (Yellow stores fat)

Bone tissue 

Bone classification

Bone Cell types

Osteocytes

•  Main cellular component of bone lie in the lacunae. 

•  Cytoplasmic processes extend from these cells, into canaliculi. 

•  Are in contact with processes of adjacent cells. 

•  Apposing cell surfaces forming communicating junctions 

•  The cells are separated from the walls of the lacunae and canaliculi by a thin layer of unmineralized matrix.

•  Contain poorly developed endoplasmic reticulum mitochondria and ribosomes and inconspicuous golgi complex.

•  Osteocytes do not secrete matrix material.

Osteoblasts

•  Located on the surface of the bone tissue & resemble epithelium(endosteum & periosteum)

•  immature bone cells which secrete the organic bone matrix - osteoid tissue.  

•  cells are ovoid, 15-20 in size with long tapering processes in contact with similar processes of adjacent cells.

•  cytoplasm is basophilic with a large amount of rough endoplasmic reticulum and a well developed Golgi.

•  cytoplasm has abundant alkaline phosphatase. 

•  Osteoblasts trapped in the osteoid matrix forms osteocytes. 

•  Osteoblasts also synthesize and secrete the organic matrix of bone. 

•  Has mesenchymal origin .

•  Cytoplasm is basophilic.

Osteoclasts

•  Found on bone surfaces where resorption of bone is taking place. (Bone growth & remodeling)

•  Are large multinucleate giant cells

•  Lie in shallow depressions known as Howship’s lacunae on the surface of the bone.          •  Cytoplasm is acidophilic.

•  Appears foamy with numerous mitochondria and lysosomes 

•  Surface of the cell adjacent to the bone being resorbed has numerous cytoplasmic processes.

•  Mitochondria tend to accumulate near this border. 

•  Origin of osteoclasts is uncertain. 

•  May be that they arise by a fusion of mononuclear cells.

Compact bone -

Lamellae may show three different patterns.

1. Haversian systems or osteones

•   Most of the lamellae are arranged as cylindrical units they run parallel to the long axis of the bone. (Osteon)

•  Are the unit structure of the bone. 

•   Each osteon consists of 8 to 15 concentric lamellae around a canal - Haversian canal 

•  It contains a neurovascular bundle. 

•  Osteons appear round or oval in transverse section.

•  Haversian canals of different osteons communicate with one another by oblique and transverse channels.

•  They also communicate with the periosteal and endosteal surface by a second system of canals, Volkman’s canals

•  Blood vessels in the Haversian canals communicate with the blood vessels of the marrow cavity via those canals

•  Canaliculi system – help in transportation of nutrient 

•   Adjacent canaliculi open into Haversian canals 

•  All the lacunae are in communication with the canal.

2. Interstitial lamellae

•  In between the osteons are irregular areas of lamellae bone 

•  Osteons and interstitial lamellae are demarcated from neighboring systems by a strongly basophilic cement line or reversal line

•  It is not traversed by canaliculi.

3. Circumferential lamellae

Outer - lies immediately beneath the periosteum. extend almost completely around most of the shaft of the bone.

Inner - A less developed system of lamellae lines the endosteum.

Between two circumferential systems, lies numerous Haversian systems and interstitial lamellae.

havasien system

Cancellous bone/ Spongy bone-

•  (Branching bone) trabeculae and spicules are thin 

•  are not traversed by blood vessels. 

•  Osteons are therefore not seen 

•  bone contains fragments of lamellar bone

Periosteum

•  Vascular membrane covering the outer surface of the bone 

•  Has the potential to form bone during bone growth and healing. 

•  Easily stripped off in young bones.

•  In adult bones it is firmly adherent particularly at the site of insertion of tendons and ligaments.

•  Periosteal fibres penetrate the surface layers of the bone as perforating fibres of Sharpey.

•  Nutrients reach the bone through vessels that enter through the nutrient foramina 

•  During growth this layer contains osteogenic cells - osteogenic layer. 

•  Periosteum has two layers.

Outer layer-

      Dense connective tissue , collagen and elastic fibres , blood vessels and nerves

Inner layer-

     More cellular, more osteoprogenitor cells, divide (mitosis) into Osteoblasts. , loose connective tissue.

Endosteum

•  Lines all internal cavities within the bone.

•  Composed of single layer of flattened osteoprogenitor cells with small amount of connective tissue.

Matrix of bone

•  Bone matrix has organic and inorganic components [contain type 1 collagen fibres 

•  It is the calcified extracellular material of bone. 

•  Compact bone consists almost entirely of extracellular substance. 

•  Osteoblasts deposit the matrix in the form of thin sheets which are called lamellae.

Bone ossification

•  Commences in fetal life by replacement of pre-existing connective tissue 

•  Controlled by GH, thyroid hormone, sex hormones

Intramembranous ossification

( Formed directly on primitive mesenchyme. Eg: Clavicle, Vault of the skull(Membranous bones) Most bones of the body )

1. All the ossification centers appear in the fibrous connective tissue

 • Mesenchyme become richly vascularized 

• proliferating actively.

• Some cells become osteoblast and secrete matrix

2. Bone matrix ( osteoid ) is secreted within fibrous membrane 

• Osteoblast entrapped in the matrix - become osteocytes 

• Initially soft & unmineralized (consists of collagen fibres & ground substance) 

• Rapidly undergoes calcification

3. Woven bone and periosteum form 

• Accumulating osteoid – between embryonic blood vessels – form network of trabeculae

• Vascularized mesenchyme condenses – become periosteum

4. Bone collar of compact bone forms & red marrow appears 

• Trabeculae just deep to the periosteum - thicken – form woven bone collar – later replaced with mature lamellar bone

• Sponge bone consisting distinct trabeculae 

• Persists internally and its vascular tissue becomes red marrow

Endochondral ossification

• Hyaline cartilaginous model is formed during embryonic life. 

• Commence at primary Centre of ossification in diaphysis 

• Condrocyte enlarge

• Matrix between the lacunae is reduced to thin fenestrated plates 

• Matrix become calcified

• Diffusion of the nutrient through calcified matrix is reduced,

• Leads to degeneration of chondrocytes and die 

• leaving large inter connecting space

At the same time,

1. Perichondrium become an osteogenic, 

2. Lays down a layer of bone around the calcified cartilage(periosteal collar) 

3. Bone formed thicken and lengthens 

4. Periosteal collar maintains the strength of the shaft 

5. Perichondrium become periosteum 

6. Vascular periosteal tissue – periosteal bud invade the calcified cartilage 

7. Buds contain blood vessels and osteogenic cells which transform to osteoblast 

8. With the death of cartilage cells , calcified cartilage erode bye osteoclasts 

9. Thin partition or trabeculae between lacunae break down forming cavities (primary marrow spaces)

10. The osteoblast arrange themselves on the surface of the calcified cartilage remnants and lay down osteoid matrix which later mineralized

11. Earliest trabeculae have a core of cartilage covered by a layer of bone 

12. With the removal of calcified cartilage by osteoclasts, the cavity expands, medullary or marrow cavity develops in the shaft

13. From primary ossific centre the process of one formation extends towards end of the model.

14. Remnant cartilage of Epiphysis continues to grow by interstitial growth resulting in an increase in length of model (mcq)

15. Secondary ossific centres – epiphyseal centers appear, usually after birth 

16. Bone formation extends all the directions 

17. At extreme end a layer of cartilage remains as articular cartilage.

Epiphyseal plate

•  Plate of cartilage persist between the epiphyseal center and the diaphyseal center 

•  Responsible for growth in length of bone.(Interstitial growth) 

•  Contain hyaline cartilage 

•  Several zones (from epiphyseal end to diaphyseal end)

Zone of resting

•  Made up of hyaline cartilage 

•  Initially long 

•  Slow growth region

Zone of proliferation

•  Active proliferation of chondrocytes 

•  Cells arrange in columns in flattened lacunae,separated by small amount of matrix  

•  Bone increases in length- interstitial growth

Zone of hypertrophy 

• Cells enlarge and accumulate glycogen

Zone of calcification

•  Thin septa calcified by deposit of hydroxyapatite 

•  Most chondrocytes die leaving spaces

Zone of ossification

•  Calcified matrix is invaded by vascular mesenchyme containing osteogenic cells 

•  The part of the diaphysis adjacent to the epiphyseal plate where bone is being laid down is the metaphysis 

•  Growth in length ceases when epiphyseal plate is replaced by bone 

•  Zone of union – epiphyseal line

Bone repair

•  When a bone fractures blood clot forms at the site

•  Capillary loops and mesenchymeal cells invade the clot and collagen is laid down forming granulation tissue

•  Mesenchymal cells differentiate into chondroblasts and osteoblasts 

•  Fibrous granulation tissue is replaced with hyaline cartilage and woven fibred bone to form provisional callus, which strengthen by deposition of calcium

•  Osteogenic cells of the endosteum and periosteum also lay down a mesh work of woven bone

•  within and around the provisional callus to form a bony callus 

•   Later by osteoclastic and osteoblastic activity lamellar bone is laid down at the site of fracture and the original form is restored

Bone healing

•  4 steps, 

1. Hematoma (fibrin clot, platelet deposition) 

2. Fibrocartilagenous callus (PMNs, macrophages, lymphocytes) 

3. Bony callus (reepithelialisation, angiogenesis, fibrogenesis) 

4. Remodelling by osteoclasts/osteoblasts (vessel regression, collagen remodelling)

Bone remodelling

•  Bone is always active and continually renews itself. 

•  Sum of osteoblastic and osteoclastic activity leads to bone growth. 

•  Spongy bone is replaced every 3-4 years. 

•  Compact bone is replaced every 10 years.

Cartilages

•  Cartilage consists of,

   * Chondrocytes (cartilage cells) 

   * Intercellular matrix 

   *  Perichondrium

•  Surrounded by a connective tissue membrane - perichondrium that contains densely arranged collagen connective tissue in outer fibrous region. Inner layer is cellular and has the potential to differentiate into young cartilage cells- chondroblasts.

•  Continued growth of perichondrium is important for the growth of cartilage 

•  Avascular, nourished by diffusion 

•  Semi rigid 

•  Predominant group substance 

•  Low metabolic activities 

•  Continued growth

Classification of cartilages

According to the nature of its fibres into

 1. Hyaline cartilage

2. White fibrocartilage 

3. Yellow elastic cartilage

Hyaline cartilage

•  Covers the articular surfaces of most synovial joints 

•  Not covered by perichondrium  Bluish purple homogenous  basophilic matrix in H & E sections 

•   Its elasticity allows to break any force applied to it. 

•   Its smooth surface allows ease of movement.

•  Eg: Most articular surfaces (epiphysis), nasal septum, tracheal ribs

White fibrocartilage

•  Similar to hyaline cartilage except that there are excessive amounts of collagen type 1 in addition to type 2 fibres in the EC matrix.

•  Few chondrocytes arranged in rows. 

•  Eg: Tendon insertion, Intervertebral disc, Pubic symphysis

Yellow elastic cartilage

•  Has a network of branching and anastomosing elastic fibres 

•  Type 2 collagen present 

•  Eg: External ear, Epiglottis, external auditory meatus.

Describe the stabilizing factors of the knee joint. (25 marks)

 Knee joint 

Introduction :-

Knee joint is the largest and most complex joint of the body, located between thigh and leg. It is a synovial joint.

Articular surfaces :-

There are three articular surfaces 

1. Condyles of the femur

2. Condyles of the tibia 

3. Patella

There is a condylar joint between the condyles of femur and tibia. 

There is a saddle joint between patella and femur.

Stability

Stability of any joint is inversely proportional to its mobility. Thus, stability of the knee joint is inversely proportional to its mobility.

Stabilizing factors :

Stability of a joint mainly depends on,

1. Shape of the articulating surfaces 

2. Ligaments 

3. Muscles around the joint

Muscles around the knee joint are the most important stabilizing factor of knee joint. They are,

• Medially - Sartorius, gracillis, semimembrinosus, semitendinosus

•  Laterally - biceps femoris , tendon of origin of popliteus

•  Posteromedially and posterolaterally - by heads of gastrocnemus

Ligament of the knee joint can be divided into two classes as intracapsulaar and extracapsular. Fibrous capsule, anterior and posterior cruciate ligaments, medial and lateral menisci and transeverse ligament are intracapsular while ligamentum patellae, tibial and fibular collateral ligaments, oblique popliteal ligament and arcuate popliteal ligament are extracapsular.

Capsule

It is very thin and weak. 

It is deficient anteriorly and replaced by quadriceps femoris, patella and ligamentum patellae. 

Capsule is attached to the margins of articular surfaces but communicate with busa around the knee joint.

capsular ligament is strengthened

•  Anteriorly - by the medial and lateral patella retinacula which are extensions from vastus medialis and lateralis.

•  Laterally - by ileotibial tract

•  Medially - by expansions from the tendons of Sartorius and semimembrinosus and by medial collateral ligament.

•  Posteriorly - by the oblique popliteal ligament.

Cruciate ligaments

-Anterior cruciate ligament begins from anterior part of intercondylar area of tibia and attached to the lateral condyle of femur. It prevents forward displacement of tibia on the femur.

-Posterior cruciate ligament begins from the posterior part of the intercondylar area of tibia and attached to the medial condyle of femur. It prevents posterior dislocation of tibia on the femur.

Menisci

They are two crescent shape fibrocartilaginous discs

They deepen the articular surfaces of the condyles of tibia.

•  Medial meniscus is larger and C shaped and attached to the capsule.

•  Lateral meniscus is smaller and circular and not adherent to the capsule

Transverse ligaments 

It connects anterior ends of medial and lateral menisci.

Ligamentum patellae

It is the continuation of quadriceps femoris tendon. It is attached above to the patella and below to the tibial tuberosity.

Tibial and fibular collateral ligaments.

Tibial collateral ligament is attached above to the medial epicondyle of the femur and below to the tibia. It is attached to the medial meniscus and to the joint capsule which prevents medial dislocation. 

Fibular collateral ligament is attached above to the lateral epicondyle of the femur and below to the head of the fibula. It is not attached to the lateral meniscus and to the joint capsule which makes lateral dislocation more common.

Oblique popliteal ligament.

Expansion from the tendon of the semimembrinosus. It blends with the posterior surface of the capsule.

Arcuate popliteal ligament

Expansion from the fibular collateral ligament arches over the tendon of popliteus to attach to the tibia.

Briefly describe the structure of skin and state how to differentiate between thick and thin skin (30 marks )

 Skin

✏  Heaviest organ in the body 

✏  Composed of epidermis and dermis

✏  Classified as thick or thin skin depending on thickness of epidermis 

✏  Keratinized stratified squamous epithelium 

✏  Regenerated by the keratinocyte stem cells in the basal layer which differentiate as they move outwards

Functions

👀  Protection: physical, biological, against UV light, from dehydration 

👀  Regulation of body temperature 

👀  Synthesis of vitamin D with UV absorption

👀  Sensory organ

Layers of Skin

Epidermis

Surface layers that are keratinized Consists of 5 layers or strata,

        1. Stratum basale (Deepest)

        2. Stratum spinosum 

        3. Stratum granulosum 

        4. Stratum lucidum 

        5. Stratum corneum (Surface)

1. Stratum Basale

👀  Single layer of columnar or cuboidal keratinocyte stem cells, which are mitotically active. 

👀  Deepest layer

👀  Attached to basement membrane by hemidesmosomes 

👀  Attached to each other with desmosomes.

👀  Melanocytes and Merkel cells present 

2. Stratum Spinosum

👀  Several layers of cuboidal, polygonal and slightly flattened cells, with a central euchromatic nucleus, mitotically active

👀  Concentrated tonofilaments in the cytoplasm 

👀  Langerhans cells 

👀  Projections of melanocytes 

👀  Cytoplasm is rich in tonofilaments that terminate with desmosomes in spiny projections, hence “spinosum” they hold the cells together and help to protect the skin from abrasions. Shrinkage of the keratinocytes reveals the spines.

3. Stratum Granulosum

👀  3to 5 layers of flattened polygonal cells 

👀  Cells accumulate keratohyalin granules with phosphorylated proteins, “granulosum” contain lamellar granules which are lipid and protein rich

👀  Are discharged extracellularly to produce a “cement” that seals the skin to foreign objects & water

👀  Most superficial layer in which nuclei are present, but no cell division occurs

4. Stratum Lucidum

👀  A translucent thin layer of extremely flattened eosinophilic cells

👀  Nuclei and organelles not present 

👀  Filaments and desmosomes retained 

👀  Cells contain eleidin, a transformation product of keratohyalin

5. Stratum Corneum

👀  Outermost layer

👀  Composed of 15 to 20 layers of cells 

👀  Flattened, non-nucleated, keratinized cells  

👀  Filled with filaments of keratin  Surface cells continuously desquamated

Epidermis - specialized cells,

Langerhans cells:

•  bone marrow derived monocyte / macrophage cell that is antigenpresenting

•  present in all layers, but predominantly in stratum spinosum

•  pale nuclei, granular cytoplasm, processed

•  increase in number in chronic inflammatory skin diseases

Merkel’s cells:

•  rare in thin skin , in the stratum basale

•  contain small dense granules

•  may function as sensory mechanoreceptors or as neuroendocrine cells

Melanocytes:

•  In the stratum basale 

•  Pale “halo” of cytoplasm 

•  Developed from neural crest 

•  Produce melanin and pass it on to nearby keratinocytes

•  Melanin covers nuclei of keratinocytes

•  Skin colour depends on activity of cells, rather than number

Dermis

👀  Dense fibro-elastic connective tissue containing glands and hair 

👀  Type I collagen  Networks of elastic fibres

👀  Blood vessels nerves & nerve endings 

👀  In old age cross linking of fibres increase and number of elastic fibres decreases 

👀  Blood vessels in skin important in blood temperature and pressure regulation

Dermal Papillae:

•  Interdigitations of the dermis and the epidermis which counteract shearing force between the two layers

•  Prominent in areas that grip or experience friction e.g. fingertips, palms, soles of feet

Layers:

•  papillary layer - loose CT that forms the dermal papillae, loops of small blood vessels and capillaries, nerve endings

•  reticular layer - dense irregular CT that forms bulk of dermis, with blood vessels and a-v shunts - for thermal regulation, lymphatics and nerves

Special Structures-Dermis

Sweat gland

1. Eccrine sweat glands (aka merocrine)

•  distributed in skin throughout the body, 

•  particularly abundant on forehead, scalp, axillae, palms and soles

•  simple coiled tubular

•  sweat is hypotonic, watery, neutral or slightly acidic

2. Apocrine sweat glands

•  large specialized sweat glands localized in axilla, areola, circumanal region 

•  begin to function in puberty and respond to hormones 

•  large coiled secretory portion: inner cuboidal cells, outer flat cells on basement membrane, wide lumen, myoepithelial cells present but not prominent

•  empty into hair follicles 

•  innervated by adrenergic fibers 

•  produce viscid milky secretions in response to external stimuli such as fear or sexual excitement

Meissner’s corpuscle

•  A specialized structured nerve ending 

•  Touch receptor 

•  Confined to dermal papillae 

•  Most numerous on hands and feet

Pacinian corpuscle

•  An encapsulated nerve ending 

•  Pressure receptor 

•  Found in deep dermis or hypodermis 

•  General Skin Nerve supply:

             • Free nerve endings detect pain and temperature 

             •  Innervation by sympathetic nervous system controls blood flow and hair

Hypodermis

👀  Loose connective tissue consisting largely of adipose tissue

Thick vs Thin skin

Thick skin:

•  on the palms, fingertips or the soles of the feet

•  lacks follicles, sebaceous glands, erector pili muscles

Thin skin:

•  is over most of the body, contains hair follicles, sebaceous glands and erector pili muscles

•  thinner epidermis

•  less well developed strata granulosa and lucida,

•  the stratum corneum may be quite thin

Sebaceous glands

👀  distributed over most of the body 

👀  on face, forehead and scalp 

👀  acinar glands with several sacs 

👀  most have short ducts that empty into neck of hair follicle, or onto the skin directly (eyelids, lips, glans penis and glans clitoris )

Hair

👀  made of keratin 

👀  follicle derived from epidermal epithelium 

👀  begins deep in dermis

👀  connective tissue sheath 

👀  sebaceous glands 

👀  medulla, cortex and cuticle 

👀  errector pili muscle -bundles of smooth muscle attached to hair follicles in dermis and papillary layer of dermis

👀  contraction elevates hairs - goose bumps

Nail

•  located on dorsal distal phalanx of each finger and toe 

•  nail plate composed of hard keratin lying on nail bed 

•  the stratum corneum of the epidermis that overlies the nail root forms the eponychium (cuticle)

•  hyponychium or nail plate consists of the stratum corneum of the underlying nail bed, and so is a keratinized epithelial layer

•  nail bed epidermis has only strata basale and spinosum 

•  growth due to cells in nail matrix at nail root

Skin anatomy

Briefly describe the blood supply of the spinal cord. (25 marks)

 Blood supply of the spinal cord

❤  Posterior spinal arteries (2) – Posterior 1/3 

❤  Anterior spinal artery – Anterior 2/3

❤  This blood supply is reinforced by; 

           1. Segmental spinal arteries (Anterior and Posterior Radicular Arteries) 

           2. Feeder arteries (Eg : Great anterior medullary artery of Adamkiewicz)

                           *  Uni lateral. 

                            * In majority, enter the spinal cord in the left side

                            * Arises in lower thoracic or upper lumbar region from aorta.

                 Spinal cord is mainly supplied by the anterior spinal artery and posterior spinal arteries. Anterior spinal artery is formed by the union of two arteries each of which are given off by vertebral arteries. It supplies the anterior 2/3 of the cord and runs in the anterior median fissure.

                There are 2 posterior spinal arteries. Each is a branch of the vertebral artery or the posterior inferior spinal artery of that side. They supply the posterior 1/3 of the spinal cord and run on either side of the posterior median sulcus.

                 Anterior and posterior spinal arteries are reinforced by small segmental arteries that lie outside the vertebral column at each inter vertebral foramen. E.g. - deep cervical, intercostal and lumbar arteries. These arteries give rise to anterior and posterior radicular arteries which follow the anterior and posterior nerve roots.Veins of the spinal cord drain into 6 longitudinally running tortuous channels which communicate with veins of the brain and venous sinuses. They drain into internal vertebral venous plexus. This plexus is valve less. It communicates with superior vena cava and inferior vena cava.

Blood supply of the spinal cord 

Describe the relations and arterial supply of the spleen. (25 marks)

 Spleen

Introduction

👀  Spleen is the largest lymphatic organ connected to blood vessels 

👀  It is wedge shaped, soft, highly vascular and dark purple in colour. 

👀  It lies between the fundus of the stomach and the diaphragm, obliquely along the long axis of 10th rib, related to 9th -11th ribs.

Relations

👀  Anteriorly, it is related to stomach. 

👀  Posteriorly, it is related to left diaphragm which separates it from pleura, left lung and 9th, 10th & 11th ribs.

👀  Inferiorly & medially , it is related to splenic flexure of colon & left kidney respectively.

👀  It has 4 impressions for related structures,

                  1.Gastric impression : for fundus of stomach

                  2. Renal impression : for left kidney

                  3. Colic impression: for splenic flexure of colon

                  4. Pancreatic impression : for tail of pancreas

👀  On inferomedial part of gastric impression, it transmits vessels and nerves. 

👀  It gives attachments to,

                    1. Gastrosplenic ligament which extend from stomach to spleen. It carries short gastric and left gastroepiploic vessels.

                    2. Lienorenal ligament which extend from kidney to spleen. It contains splenic vessels and pancreatic tail.

Blood supply

👀  Spleen is supplied by splenic artery which is the largest branch of coeliac trunk. 

👀  It is tortuous in its course. 

👀  It passes through the lienorenal ligament to reach the hilum of spleen. 

👀  It divides into trabecular arteries that runs along the trabeculae into the splenic pulp

👀  When they leave the trabeculae to enter the parenchyma, they branch into central arteries which are enveloped Periarteriolar lymphoid sheath (PALS ).

👀  Each central artery leaves the white pulp & enters the red pulp, branching into penicillar arteries, which are right angles to central arteries.

👀  Near the termination, they form ellipsoid arteries. 

👀  Beyond them are sheath capillaries which are small blind ended capillaries with no endothelial lining, surrounded by aggregate of macrophages.

👀  Blood flow through splenic red pulp can take either of two,

Closed circulation :- Capillaries open directly to sinusoids. Blood always inside vessels.

Open circulation :- Prolongation of penicillar arteries into splenic cords & blood passes through spaces between cells to reach sinusoids.

Microscopic structure of spleen 

Describe the microscopic structure of the spleen. (25 marks)

 Spleen

Introduction

👀  Spleen is an encapsulated secondary lymphoid organ in the body.

👀  It consists of connective tissue capsule, trabeculae & cellular parenchyma/ Splenic pulp.

Capsule

👀  Spleen is surrounded by a capsule of dense connective tissue with smooth muscle fibers.

👀  Short trabeculae extend from there dividing parenchyma into incomplete compartments.

👀  Large trabeculae originate at the hilum – carrying blood vessels, nerves &lymphatics. 👀  Inter trabecular space is filled by reticular fibers/cells.

Splenic parenchyma

👀  Splenic pulp has 2 components, lymphoid aggregation, called white pulp & vascular tissue, called red pulp.

👀  White pulp consists of Periarteriolar lymphoid sheath (PALS ) & Lymphoid nodules.

👀  The splenic artery divides into trabecular arteries that runs along the trabeculae into the splenic pulp.

👀  When they leave the trabeculae to enter the parenchyma, they branch into central arteries which are enveloped by a sheath of T lymphocytes called, Periarteriolar lymphoid sheath (PALS ) which is a part of white pulp.

👀  After coursing through the parenchyma for variable stretches, the PALS receive large collections of B lymphocytes, forming Lymphoid nodules.

👀  Therefore, lymphocytes in the nodules are B lymphocytes. 

👀  In growing nodules the central artery is pushed to an eccentric position. 

👀  Marginal zone is the interphase between lymphoid nodule & red pulp & it consists of many blood sinuses & loose lymphoid tissue.

👀  Each central artery leaves the white pulp & enters the red pulp, branching into penicillar arteries, which are right angles to central arteries.

👀  Near the termination, they form ellipsoid arteries. 

👀  Beyond them are sheath capillaries which are small blind ended capillaries with no endothelial lining, surrounded by aggregate of macrophages.

👀  Red pulp consists of Splenic sinusoids which are thin wall, wide venous vessels & Splenic cords

👀  Splenic Sinusoids are lined by elongated endothelial cells with highly discontinuous basal lamina.

👀  Splenic cords(Billroth’s cords), are cell cords lying between sinusoids. 

👀  It consists of mainly macrophages & reticular fibers & rich in B & T lymphocytes, plasma cells, granulocytes & platelets.

👀  Blood flow through splenic red pulp can take either of two,

Closed circulation 

                Capillaries open directly to sinusoids. Blood always inside vessels.

Open circulation

                 Prolongation of penicillar arteries into splenic cords & blood passes through spaces between cells to reach sinusoids.

👀  Lymph vessels originate mainly in trabeculae. 

👀  Veins derived from parenchyma. 

👀  From the sinusoids, blood drains into red pulp veins & then into trabecular veins, which in turn form the splenic vein.

Cross section of the spleen

Describe the gross anatomy of the middle ear. (25 marks)

 Middle ear

                 Middle ear is an air filled space in the petrous part of the temporal bone. It is cube – shaped with six sides namely the roof, medial wall, lateral wall, anterior wall & the posterior wall. Inside it is lined by mucus membrane, within the cavity 3 ear ossicles maleus, incus and stapes are seen, along with tensor tympani and stapedius which are the muscles of the middle ear.

👀  The roof of the cavity separates the middle ear from the middle cranial fossa and the temporal lobe of the brain. It is formed by a thin bony plate called Tegmen tympani. This surface is also known as Tegmental wall.

👀  The floor is also formed by a thin plate of bone beneath which lies the superior bulb of the mental jugular vein. The tympanic branch of the Glossopharyngeal nerve pierces the floor to form the tympanic plexus.

👀  Lateral wall is formed by the Tympanic membrane and it separates the middle ear from the external auditory meatus. Malleus is attached to this surface.

👀  Medial wall or the labyrinthine wall separates this cavity from the inner ear. It has an oval window, to which the foot piece of stapes attached, round window which is closed by the secondary tympanic membrane, “promontory” formed by the 1st part of the cochlea and also a prominence formed by the facial canal.

👀  Anterior wall is formed by the approximation of lateral & medial walls and the roof descending. It separates the cavity and the internal carotid artery upper most part has an opening for the tensor tympani muscle. In the middle there is another opening for the auditory tube.

👀  The posterior wall allows direct communication of the middle ear and the mastoid antrum via the auditus (Mastoid antrum is an air filled space in mastoid process). In this surface there are numerous prominences formed by facial canal, pyramidal eminence, tendon of stapedius & chorda tympani.

👀 Infections of the middle ear could get spread to mastoid air cells, cerebellum or sigmoid sinus since they are posterior relation of the cavity and are open via auditus.

Middle ear

Describe the course and distribution of the facial nerve.

                       Cranial Nerves

12 pairs of cranial nerves. Passes through the foramina, fissures in the skull.

1. Olfactory nerve - cribriform plate of ethmoid

2. Optic nerve - optic canal

3. Oculomotor nerve - superior orbital fissure

 4. Trochlear nerve - superior orbital fissure

5. Trigeminal nerve 

     i. Ophthalmic - superior orbital fissure

     ii. Maxillary - foramen rotundum

    iii. Mandibular Pons - foramen ovale

6. Abducent nerve - superior orbital fissure

7. Facial nerve - internal acoustic meatus, facial canal, stylomastoid foramen

8. Vestibulocochlear nerve - internal acoustic meatus

9. Glossopharyngeal nerve - jugular foramen 

10. Vagus nerve - jugular foramen

11. Accessory nerve - jugular foramen

12. Hypoglossal nerve - hypoglossal canal

👀 Some cranial nerves are sensory  Eg: 1,2,8

👀 Some cranial nerves are motor  Eg: 3,4,6,11,12

👀 Some cranial nerves are both  Eg: 5,7,9,10

 Cranial nerves have NO SYMPATHETICS. Some possess parasympathetics

 Eg:

         i. Oculomotor nerve  - Edinger Westphal nucleus

        ii. Facial nerve  - Superior salivatory and lacrimal nuclei 

        iii. Glossopharyngeal nerve  -  Inferior salivatory nucleus 

         iv. Vagus nerve  -  Dorsal nucleus of vagus

 Optic nerve is an outgrowth of brain that emerges from the diencephalon – not from the brainstem as other cranial nerves

 There are only 9 pairs of cranial nerves that emerge solely from the brainstem

                          Facial Nerve

Sensory and motor

3 nuclei

1. sensory 

            In upper part of tractus solitarius (7,9,10) - supplies taste fibres from anterior 2/3 of tongue, floor of mouth & palate

2. main motor

           In lower part of pons -muscles of facial expression, auricular

muscles, Stapedius, posterior belly of digastric, stylohyoid

3. parasympathetic

         *  lacrimal nucleus – lacrimal gland

         *  Superior salivatory nucleus - submandibular gland, sublingual gland,nasal & palatine glands

Facial Nerve

👀  The facial nerve consist of a motor and a sensory root. The fibers of the motor root first travel posteriorly around the medial side of the abducent nucleus.

👀 Then they pass around the nucleus beneath the facial colliculus in the floor of the 4 th ventrical and finally pass anteriorly to emerge from the brain stem between the pons and medulla oblongata.

👀  They pass laterally in the posterior cranial fossa with the vestibular cochlear nerve and enter in to internal acoustic meatus.

👀  At the bottom of the meatus, the nerve enters the facial canal and runs laterally through the inner ear.

👀  On reaching the medial wall of the tympanic cavity, the nerve expand to form the sensory geniculate ganglion and tern sharply backward above the promontory.

👀  At the posterior wall of the tympanic cavity the facial nerve tern downward on the medial side of the aditus of the mastoid antrum, descend behind the pyramids, and emerge from the stylomastoid foramen.

👀  At the geniculate ganglion, lacrimatory fibers of the superior salivatory and lacrimatory nucleus get separated and form the greater petrosal nerve.

👀  Then it enter in to middle cranial fossa and leave it through foramen lacerum. 

👀 At the midway of the foramen lacerum it enter in to pterigoid canal with deep petrosal nerve.

👀  Then it enter in to pterigoid ganglion and supply to the lacrimal glands. 

👀  Main motor fibers of the facial nerve supply to the stapedius muscle before emerge from the stylomastoid foramen.

👀  Chorda tympani nerve runs through middle ear between malleus and incus and enter in to infra temporal fossa.

👀  Then it accompanies the lingual nerve.

👀  Fibers from the tractus solitarius nucleus supply to anterior 2/3 of tongue and Fibers from superior salivatory nucleus supply to both sublingual and submandibular gland.

👀  After emerge, between stylomastoid foramen motor fibers supply to the stylohyoid, posterior belly of digastrc, auricular muscles, and whole facial expression muscles exept levator palpebrae superioris.

Clinical

Supranuclear (UMN) lesion

                    - As the upper part of the face receives corticonuclear fibres from both cerebral hemispheres(bilateral innervation)

                    - Only lower part of opposite side of face is paralyzed.                                                                  - Loss of taste

Infranuclear (LMN) lesion

                     - Whole face of same side get paralyzed.                                                                                           - Lower eyelid will drop.                                                                                                                       - Wrinkles disappear in forehead.                                                                                                       - Food accumulate teeth & cheek.

Anatomy of the cavernous sinus.

                  Cavernous Sinus 

                Cavernous sinus is a dural venous sinus situated in the middle cranial fossa between the two layers of Dura mater. There are two sinuses on either side of the body of the sphenoid bone. They are connected to each other via anterior and posterior inter cavernous sinuses running on either side of the pituitary stalk on the diaphragma sellae. The inside of the sinus is divided into spaces by trabaculae. Each sinus extends from the superior orbital fissure to the apex of the petrous part of temporal bone. Internal carotid artery surrounded by sympathetic nervous plexus and the abducent nerve runs through the middle of the sinus. Abducent nerve is inferolateral to the artery. They are separated from the blood by the endothelial lining of the sinus.

                            Optic nerve, Trochlear nerve, Ophthalmic nerve and Mandibular nerve run in the lateral wall of the sinus from top to bottom in order. They lie between the endothelial ling and the Dura mater.

                             Superior and inferior ophthalmic veins, inferior cerebral veins, the sphenoparietal sinus and the central vein of the retina drain into it. The cavernous sinus posterior drains into superior and inferior petrosal sinuses and inferiorly in to pterygoid venous plexus through emissary veins.

                               Cavernous sinus is superiorly related to optic tract, optic chiasma, internal carotid artery and olfactory tract. It is medially related to pituitary gland and sphenoidal air sinus. It is inferiorly related to foramen lacerum and laterally related to temporal lobe.

Cavernous sinus

Clinicals

👀 Thrombosis of cavernous sinus

               - Caused by sepsis in dangerous area of face, nasal cavities, paranasal air sinuses                 - Nervous symptoms – Severe pain in eye and forehead (ophthalmic nerve)                              Paralysis of ocular muscles (3rd, 4th and 6th cranial nerves)

               - Venous symptoms – Oedema of eyelids, cornea, root of nose Exophthalmos

👀 Pulsating exophthalmos

               - In head injury, a communication between cavernous sinus and internal carotid                   artery may occur.

              - Eyeball protrudes and pulsates with each heartbeat.

Venous sinuses

*  Lie between the inner meningeal and outer endosteal layers of dura mater – except inferior sagittal & straight sinuses (between inner layers)

*  Receives all the blood from the Brain, Meninges, Bones of skull

 *  Communicates with diploe veins of the skull and veins of scalp via emissary veins

 *  Lined interiorly by endothelium 

*  Do not contain valves 

*  No muscle tissue in walls

1.Superior sagittal sinus

  Inferior sagittal sinus

2. Straight sinus

3. Transverse sinus

4. Sigmoid Sinus

5. Occipital sinus

6. Basilar plexus

7. Cavernous sinus 

Describe the structural adaptations of the skin to its function.

❤ The main functions of the skin are protection, regulation of body temperature and synthesis of vitamin D.

❤ It also functions as sensory organ. 

❤It consists of 3 layers known as epidermis, dermis and hypodermis. 

❤ The epidermis is of stratified squamous keratinized type of epithelia. 

❤ It consists of 5 layers. They are, 

❤ Stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, stratum corneum from deep to the most superficial.

❤The stratum basale is the deepest layer. It consists of a single layer of columnar or cuboidal cells.

❤ Keratinocyte stem cells are scattered among other cells. The cells are attached to the basement membrane by hemidesmosomes while they are attached to eachother by desmosomes.

❤This firm attachment to membrane and to eachother provides protection. 

❤ Melanocytes and Merkel cells are also present. 

❤ Melanocytes produce pigment melanin that determines the skin colour. 

❤ Merkel cells aid the skin to act as a sensory organ by functioning as sensory mechanoreceptors.

❤The stratum spinosum consist of several layers of polygonal cells which are mitotically active. They contain concentrated tonofilaments.

❤Langerhan cells are scattered among the polygonal cells. 

❤ They are antigen recognizing and processing cells and help to protect the body against antigens. Processes of melanocytes project into the layers of this stratum.

❤The polygonal cells are attached to each other by desmosomes and this firm attachment protects the skin against abrasions.

❤The stratum granulosum consists of 3-5 layers of flattened polygonal cells which contain keratohyalingranules. The cells are not mitotically active.

❤The stratum lucidum is a translucent thin layer of extremely flattened eosinophilic cells. 

❤They do not contain nuclei or any organelles. 

❤Filaments and desmosomes are retained. 

❤ Cells contain eleidin. 

❤Stratum corneum is the outermost layer and is composed of 15-20 layers of cells. 

❤The cells are flattened, non-nucleated and keratinized. 

❤The cells are filled with keratin filaments. 

❤ Keratinization aids in providing protection against abrasions. 

❤The dermis is formed from dense irregular connective tissue.  Interdigitations of the dermis and the epidermis are called dermal papillae. 

❤ They are important in opposing shearing forces between the two layers thus ensuring protection. There are two layers in the dermis as the papillary layer and the reticular layer.

❤ The papillary layer consist of loose connective tissue, loops of small blood vessels, capillaries and nerve endings.

❤The reticular layer consists of dense irregular connective tissue, blood vessels that form av shunts, nerves and lymphatics.

❤ The blood vessels aid in temperature regulation. 

❤ While the nerve endings acting as a sensory organ. 

❤Meissner’s corpuscles, which are confined to dermal papillae act as touch receptors further enabling the skin to act as sensory organ.

❤Pacinian corpuscles, which are found in deep dermis or hypodermis act as pressure receptors. It also enhances the ability of skin to act as a sensory organ. 

❤ Sweat glands are also present in the dermis and aid in temperature regulation.

Describe the macroscopic and microscopic structure of the intervertebral dis.

          Intervertebral disc which lies between adjacent vertebral bodies,is primarily composed of fibrous cartilage.It attaches to the vertebrae via thin layers of hyaline cartilage,which are called end plates. It has two components; the peripheral annulus fibrosus and central nucleus pulposus.Nucleus pulposes occurs more towards the posterior margin of the disc.Intervertebral disc acts as a lubricated cushions and shock absorbers in the spinal cord.

Nucleus pulposus and annulus fibrosis 

Nucleus pulposus 

Gelatinous. Has more ground substance rich in hyaluronic acid.Consisted of notocordal cells.Avascular and nourished via the cartilaginous end plates.Important as a shockabsorber.

Anulus fibrosis 

Is made of fibrocartilage.Rich in bundles of type 1 collagen.Those fibers create sheets.The peripheral fibers attach to the anterior and posterior longitudinal ligaments.The matrix contains less ground substance.Cartilagenous cells are less numeric.Only the outer part of annulus fibrosus has a blood supply.Is derived from sclerotomal cells.