SPECIAL: CARDIO AND LYMPH

Question 1

General structure and classification of blood vessels

Answer 1

Opening bitch:

• Blood vessels are an integral component of the circulatory system.
• The five types of blood vessels are (in order of circulation):
  
  • Arteries
  • Arterioles
  • Capillaries
  • Venules
  • Veins.
• Large blood vessels (i.e., arteries and veins)
  
  • The primary function:
    
    • Is the transport of blood to and from the heart
• Smaller blood vessels (e.g., capillaries)
  
  • Enable substance exchange between the cells and blood.
• Arteries
  
  • Carry oxygen-rich blood from the heart to the periphery.
    
    • Exceptions:
      
      • Pulmonary artery
      • Umbilical arteries of fetal circulation
• Capillary bed
  
  • Enables the delivery of oxygen and nutrients to the surrounding tissues.
• Postcapillary venules join together to form veins,
  
  • Which deliver oxygen-poor blood back to the heart.

Both arteries and veins are composed of the same three layers of tissue: Overview:

1- Tunica intima: endothelium, basal lamina of endothelial cells, subendothelial layer

2- Tunica media: smooth muscle layer

• In arteries: internal and external elastic membrane (fernistrated, in circular concentric layers
• Containing variable amounts of elastin reticular fibers proteoglycans between the layers of smooth muscle

3- Tunican adventita: longitutally arranged collagenous tissue with elastic fibers

• In large arteries and viens:
  
  • Vasa vasorum, supplying to the vascular walls
  • Nervi vascularis: controls contracrion of smooth muscle

Tunica Intima

• Endothelium:
  
  • Simple squamous endothelial cells resting on basal lamina
  • Longitudinal dirrection
• Subendothelial layer:
  
  • Loose connective tissue with isolated smooth muscle cells
    
    • Longitudinal arrangement
    • (fibroblasts, smooth muscle cells, ECM)
• Internal elastic membrane:
  
  • Feristraed elastic material
  • Only in arteries
    
    • Boundry between tunica media and intima
  • Technically part of the tunica intima but composed of elastic fibers produced by smooth muscle cells in the tunica media.

Tunica media

• Muscular layer:
  
  • Circullarly arranged smooth muscle cells
  • Smooth muscle cells secrete: intercellular mass with reticular and elastic fibers, ECM
  • Contains alpha and beta adrenergic receptors.
    
    • Innervated primarily by the sympathetic nervous system.
    • Stimulation of the alpha receptors produces contraction of the smooth muscles.
    • Stimulation of the beta receptors produces dilatation of the vessel
• Pericytes – correspond to tunica media in capillaries and postcapillary venules
• External elastic membrane:
  
  • This layer usually only appears in large arteries.

Tunica adventitia

• Collagen and elastic fibres, longitudinal orientation
  
  • Attaches vessel to neighboring structures
• Vasa vasorum – penetrate through tunica adventitia into tunica media lymphatic capillaries – media of veins and adventitia of arteries
• Nervi vasorum
  
  • autonomic nerve branchs
  • contril contraction of smooth muscle

Arteries VS Viens:

• Blood pressure
  
  • A:High
  • L: Low
• Intima
  
  • A: No valves
  • L: Forms valves to prevent retrograde blood flow
• Media
  
  • A: The thickest layer
    
    • Contains more smooth muscle cells or elastic fibers depending on the type of the artery
  • V: Fewer smooth muscle cells
• Adventitia
  
  • A: Relatively thin
  • V:Thick compared to other layers
• Absent external elastic lamina
• Internal and external elastic membrane:
  
  • A: well visable border
  • V: absent

Extra… diffrent questions tachles

Arteries varations:

• Location
  
  • Elastic arteries:
    
    • Vessels close to the heart (aorta , pulmonary trunk, and their large branches)
  • Muscular arteries
    
    • Vessels farther from the heart (e.g., brachial artery, femoral artery)
• Components of the tunica media
  
  • Elastic arteries:
    
    • Primarily elastic fibers
  • Muscular arteries
    
    • Primarily smooth muscle
• Function
  
  • Elastic arteries:
    
    • Absorb energy of left ventricular contraction of the heart during systole → dampen pulsatile blood flow to reduce the difference in blood pressure between systole and diastole
  • Muscular arteries
    
    • Regulate blood flow through the lumen by changing vascular resistance (i.e., resistance vessels)

Endothelial cells:

• Simple SQ, polygonal shape, lines all vessels and heart cavities
• Alinged with direction of blood flow
• Sitiated on basal lamina, joined together by tight junctions with partial ability to contract
• Function:
  
  • Selective permiabilty barrier between blood and tissues
  • Antithrombogenic surface: prevent platlet aggregation- cloting)
  • Enzymatic functions: inactivation/activation of mediators, lipolysis of lipoproteins
  • Secretion of vasoactive factors, modulation of blood flow
    
    • endothelin- constricor
    • nitric oxide (NO)- vasodilator
  • Passage of cells – diapedesis

Question 2

Structure of the capillaries, types of arrangement of the capillary bed FML!

Answer 2

Opening

• Blood vessels are an integral component of the circulatory system.
• The five types of blood vessels are (in order of circulation):
  
  • Arteries
  • Arterioles
  • Capillaries
  • Venules
  • Veins.
• Large blood vessels (i.e., arteries and veins)
  
  • The primary function:
    
    • Is the transport of blood to and from the heart
• Smaller blood vessels (e.g., capillaries)
  
  • Enable substance exchange between the cells and blood.
• Arteries
  
  • Carry oxygen-rich blood from the heart to the periphery.
  • Exceptions:
    
    • Pulmonary artery
    • Umbilical arteries of fetal circulation
• Capillary bed
  
  • Enables the delivery of oxygen and nutrients to the surrounding tissues.
• Postcapillary venules join together to form veins,
  
  • Which deliver oxygen-poor blood back to the heart.

Capillaries- General:

• Are the terminal branchs of blood stream, forming network between cells in tissues
• Function:
  
  • Exchange of gases and nutrients with tissue (density of distribution of capillaries varies depending on the region/organ)
  • Capillary bed:
    
    • Site of substance capillary fluid exchange between blood and tissue in accordance with Starling forces
• Charactersitcs
  
  • Large total cross-sectional area
  • Low blood flow velocity
  • Short diffusion path composed of a single layer of endothelial cells and a basal lamina

Structure (from inner to outer layer)

• Endothelial cells (single layer)
• Pericytes
• Basement membrane
  
  • Not all capillaries have a continuous basement membrane.
• The exact structure of capillaries depends on the required substance exchange of the surrounding tissue

1- Endothelium

• One layer of flattened cells, polygonal shape, lines all vessels and heart cavities
  
  • Various types of endothelial cells
  • Connected by zonula adherens and tight junctions, which enable the intercellular transport of substances according to junction permeability.
  • (e.g Endothelium makes up part of the blood-brain barrier. The dense tight junctions between endothelial cells prevent paracellular transport through the brain capillaries.)

2- Basal lamina

Not all capillaries have a continuous basement membrane.

3- Pericytes

​Pericytes rest on the outside of the endothelium and form a discontinuous wall.

• elongated vell body
• many proturusions around vessel
• medium eosiniphillic
• contaction capability: actin, myosin, tropomyosin in cytoplasm
• have their own basal lamina

Classification of capillaries

1) Continuous (somatic) capillaries
2) Visceral capillaries:
- fenestrated (with diaphragm)
- fenestrated (without diaphragm)
- sinusoidal capillaries (discontinuous)

1) Continuous (somatic) capillaries

• Predominant capillary type in most organs
• Continuous endothelium without capillaries and pores
• BL: continous, non interupted
• Brain, skin, lung, muscle, thymus

​

2) Visceral capillaries:

• Fenestrated (with diaphragm)
  
  • Endothelium contains fenestrations
    
    • Fenestrations are spanned by a diaphragm with a negative charge
      
      • Diaphragm fromed from glycocalyx from the pincotytoic vessels (incomplete membrane)
  • Basal lamina is continuous
  • Function:
    
    • Passage of water and hydrophilic molecules possible
      
      • Passage of plasma proteins difficult because of their negative charge
  • Location:
    
    • Intestine, endocrine glands, kidney (peritubular)
      
      • Sites of fluid and metabolite absorption
• Fenestrated (without diaphragm)
  
  • Endothelial cells contain pores
    
    • Pore= true opening which is not covered or sipported by anything
  • Continous basal lamina
  • Location:
    
    • Glomeruli, capillary beds found in the Bowman’s capsule of the kidneys
• ​​Sinusoidal capillaries (discontinuous)
  
  • Endothelium cells contain fernistrations and pores
  • Basal lamina is not continuous
  • Larger lumen, more irregularrly shaped
  • Function:
    
    • Passage of macromolecules
    • As a result of their discontinuous wall structure, sinusoidal capillaries enable the transfer of cells produced in the bone marrow into the blood, for example.
  • Location:
    
    • Liver, bone marrow, placenta, and spleen
• Specillized cells in liver that occur in association with the endothelial cells.
  
  • Kupffer cells (stellate sinusoidal macrophages)
  • Ito Cells: vitamin A storing (hepatic stellate cells)

Endothelial cells:

Simple SQ, polygonal shape, lines all vessels and heart cavities

Alinged with direction of blood flow

Sitiated on basal lamina, joined together by tight junctions with partial ability to contract

Function:

Selective permiabilty barrier between blood and tissues

Antithrombogenic surface: prevent platlet aggregation- cloting)

Enzymatic functions: inactivation/activation of mediators, lipolysis of lipoproteins

Secretion of vasoactive factors, modulation of blood flow

endothelin- constricor

nitric oxide (NO)- vasodilator

Passage of cells – diapedesis

Question 3

Structure of the arterial wall

Answer 3

Opening

• Blood vessels are an integral component of the circulatory system.
• The five types of blood vessels are (in order of circulation):
  
  • Arteries
  • Arterioles
  • Capillaries
  • Venules
  • Veins.
• Large blood vessels (i.e., arteries and veins)
  
  • The primary function: Is the transport of blood to and from the heart
• Smaller blood vessels (e.g., capillaries)
  
  • Enable substance exchange between the cells and blood.
• Arteries
  
  • Carry oxygen-rich blood from the heart to the periphery.
  • Exceptions:
    
    • Pulmonary artery
    • Umbilical arteries of fetal circulation
• Capillary bed
  
  • Enables the delivery of oxygen and nutrients to the surrounding tissues.
• Postcapillary venules join together to form veins,
  
  • Which deliver oxygen-poor blood back to the heart.
• Both arteries and veins are composed of the same three layers of tissue

1- Tunica intima: endothelium, subendothelial layer

2- Tunica media: smooth muscle layer

3- Tunican adventita: loose CT

Tunica Intima

• Endothelium:
  
  • Simple squamous endothelial cells resting on basal lamina
  • Longitudinal dirrection
• Subendothelial layer:
  
  • Loose connective tissue with isolated smooth muscle cells
  • Longitudinal arrangement
  • (fibroblasts, smooth muscle cells, ECM)
• Internal elastic membrane:
  
  • Feristraed elastic material
  • Only in arteries
  • Boundry between tunica media and intima
  • Technically part of the tunica intima but composed of elastic fibers produced by smooth muscle cells in the tunica media.
• Tunica media
  
  • Muscular layer:
    
    • Circullarly arranged smooth muscle cells
      
      • Smooth muscle cells secrete: intercellular mass with reticular and elastic fibers, ECM
    • The thickest layer in arteries
      
      • Contains more smooth muscle cells or elastic fibers depending on the type of the artery
      • Less developed in viens
      • Contains alpha and beta adrenergic receptors.
        
        • Innervated primarily by the sympathetic nervous system.
        • Stimulation of the alpha receptors produces contraction of the smooth muscles.
        • Stimulation of the beta receptors produces dilatation of the vessel
  • External elastic membrane:
    
    • This layer usually only appears in large arteries.
• Tunica adventitia
  
  • Collagen and elastic fibres, longitudinal orientation
  • Attaches vessel to neighboring structures
  • Thin layer in arteries, in viens more prominent
    
    • Vasa vasorum – penetrate through tunica adventitia into tunica media lymphatic capillaries – media of veins and adventitia of arteries
    • Nervi vasorum
      
      • Autonomic nerve branchs
      • Contraction of smooth muscle

​

Arteries varations:

Elastic, muscular, arterioles

• Location
  
  • Elastic arteries:
    
    • Vessels close to the heart (aorta , pulmonary trunk, and their large branches)
  • Muscular arteries
    
    • Vessels farther from the heart (e.g., brachial artery, femoral artery)
• Components of the tunica media
  
  • Elastic arteries:
    
    • Primarily elastic fibers
  • Muscular arteries
    
    • Primarily smooth muscle
• Function
  
  • Elastic arteries:
    
    • Absorb energy of left ventricular contraction of the heart during systole → dampen pulsatile blood flow to reduce the difference in blood pressure between systole and diastole
  • Muscular arteries
    
    • Regulate blood flow through the lumen by changing vascular resistance (i.e., resistance vessels)

​

Arterioles

• 50-300 μm, 1-5 layers of smooth muscle cells
• Thin tunica adventita

Question 4

Structure of the venous wall

Answer 4

Opening

• Blood vessels are an integral component of the circulatory system.
• The five types of blood vessels are (in order of circulation):
  
  • Arteries
  • Arterioles
  • Capillaries
  • Venules
  • Veins.
• Large blood vessels (i.e., arteries and veins)
  
  • The primary function: Is the transport of blood to and from the heart
• Smaller blood vessels (e.g., capillaries)
  
  • Enable substance exchange between the cells and blood.
• Arteries
  
  • Carry oxygen-rich blood from the heart to the periphery.
  • Exceptions:
    
    • Pulmonary artery
    • Umbilical arteries of fetal circulation
• Capillary bed
  
  • Enables the delivery of oxygen and nutrients to the surrounding tissues.
• Postcapillary venules join together to form veins,
  
  • Which deliver oxygen-poor blood back to the heart.

As I said…

Veins main function:

• Transportation of venous (deoxygenated) blood from the periphery to the heart
• Exceptions:
  
  • Pulmonary veins
  • Umbilical veins of fetal circulation
• Course: capillary → venule → vein
• Characteristic feature:
  
  • Veins are known as capacitance vessels because they are capable of storing a significantly larger volume of blood than arteries due to their large lumen and high compliance.

Structure:

• Tunica Intima
  
  • Endothelium:
    
    • Simple squamous endothelial cells resting on basal lamina
    • Longitudinal dirrection
  • Subendothelial layer:
    
    • Loose connective tissue with isolated smooth muscle cells
    • Longitudinal arrangement
    • (fibroblasts, smooth muscle cells, ECM)
  • Forms valves to prevent retrograde blood flow
  • *** No internal and external feristraed elastic material
• Tunica media
  
  • Muscular layer:
    
    • Circullarly arranged smooth muscle cells
    • Smooth muscle cells secrete: intercellular mass with reticular and elastic fibers, ECM
    • **The thickest layer in arteries
    • Less prominet in veins, fewer smooth muscle cells
      
      • Contains alpha and beta adrenergic receptors.
      • Innervated primarily by the sympathetic nervous system.
        
        • Stimulation of the alpha receptors produces contraction of the smooth muscles.
        • Stimulation of the beta receptors produces dilatation of the vessel
  • Pericytes – correspond to tunica media in capillaries and postcapillary venules WTF?
• Tunica adventitia
  
  • Collagen and elastic fibres, longitudinal orientation
  • Attaches vessel to neighboring structures
  • Thick compared to other layers and in comparison to arteries
    • Vasa vasorum – penetrate through tunica adventitia into tunica media lymphatic capillaries – media of veins and adventitia of arteries
    • Nervi vasorum
      
      • autonomic nerve branchs

Classification of viens:

• Venules
  
  • Diameter as small as 0.1 mm.
  • Function:
    
    • Collect blood from capillaries to transfer to veins
  • Further classification:
    
    • Postcapillary venules
      
      • Are located directly following a capillary bed
      • Structure resembles that of capillaries (allowing high permeability and substance exchange)
    • Collecting venules :
      
      • Precede the collecting veins
      • Structure resembles that of larger blood vessels (i.e., with three layers)
    • High endothelial venules
      
      • Possess special surface molecules for leukocyte recognition, which are the sites of leukocyte extravasation into or from lymphatic organs
• Small veins, collecting viens
  
  • Less then 1 mm in diameter and are continuous with muscular venules.
• Medium veins
  
  • Represent most of the named veins in this category.
  • They usually are accompanied by arteries and have a diameter of as much as 10 mm.
• Large veins
  
  • Usually have a diameter greater than 10 mm.
  • Examples of such veins include the superior and inferior vena cava and hepatic portal vein.

Venules

• Postcapillary venules: diameter up to 50 μm, pericytes

Common type veins

Muscular type veins

• Inferior and superior VC, portal, brachiocephallic, renal viens
• collapsed lumen
• Intima: endothelium, subeldothelial tissue
• Media: CT, smooth muscle cell in lognitduinal ??
• Adventita: thickest layer, loose CT, bundles of smooth muscle cells ???

Question 5

Structure of the heart, conducting system of the heart

→

Innervated by the phrenic nerve

Answer 5

Opening:

• The heart is a muscular organ located in the middle mediastinum that pumps blood through the circulatory system.
• Characteristics of the heart:
  
  • Two ventricles and two atria, which connect the pulmonary circulation with the systemic circulation
  • Four valves, which ensure that blood flow occurs in only one direction
  • Roughly the size of a fist
  • Surrounded by pericardium (a fibroserous, fluid-filled sac)
  • Location: in the middle mediastinum between the lungs

Layers of the heart

The heart wall itself consists of three layers (from inside to outside):

• Endocardium
• Myocardium
• Epicardium:
  
  • Connective tissue layer attached to the outside of the myocardium,
  • i.e., visceral layer of serous pericardium
• Pericardium: membrane that directly surrounds the heart

1- Endocardium

• Innermost layer of heart tissue: lining of the heart chambers, corrisponds to tunica intima of vascular walls
• Consisting of the following sublayers:
  
  • Endothelium (innermost):
    
    • Simple squamous epithelium
  • Subendothelial layer:
    
    • A layer of loose connective tissue
  • Myoelastic layer/ elastic-muscular layer:
    
    • Another layer of loose CT, differs from the pervious layer by the pressence of elastic fibers and myofibroblasts
  • Subendocardium (outermost):
    
    • Loose connective tissue containing:
    • Veins and nerves
    • Cardiac Purkinje cells
      
      • Specialized/modified cardiomyocytes that are part of the conducting system of the heart
      • Contain fewer contractile myofibrils and more mitochondria, glycogen, and gap junctions than normal cardiomyocytes.

2-Myocardium

• Sheets of myocardium separated by perimysial loose connective tissue
  
  • Myocardium of the atria is substantially thinner than that of the ventricles.
  • Atria: receive blood from the large veins and deliver it to adjacent ventricles: requires relatively low pressure.
  • Ventricles: require higher pressure to pump the blood through the pulmonary and systemic circulations
• Cardiomyocytes:
  
  • Atriated muscle cells containing a single, centrally located nucleus
  • Contain many mitochondria, which produce ATP for contraction.
  • Connected by intercalated discs to form long fibers.
    
    • They contain adherent junctions (transmit mechanical stimuli) and gap junctions (transmit electrical stimuli)
• Fibroblasts (these become myofibroblasts after injury)
• Extracellular matrix: collagen, elastin, and glycosaminoglycans
• Damaged myocardial tissue is replaced by noncontractile scar tissue (fibrosis) that does not conduct electrical impulses well and, thus, predisposes to cardiac arrhythmias.

3-Epicardium:

• =The visceral layer of serous pericardium
  
  • Outermost layer of the heart wall
  • Separated from the parietal layer of the serous pericardium by the pericardial cavity.
  • Subepicardial layer: adjacent to myocardium
    
    • Loose CT with significant amount of adipose cells
    • Contain blood vessles and nerves supplying heart
      
      • numerous coronary blood vessels (15), which vary in amount in different regions of the heart.
  • ​Lamina propria
    
    • Loose CT with elastic fibers, nerves and capillaries
  • Mesothelium- most outer!
    
    • secrete a small amount of serous fluid, which lubricates the sliding friction of the epicardium against the parietal pericardium during contraction and relaxation of the heart

EXTRA———————————————–

Pericardium= Fibroserous- serous membrane enclosing the heart

• Due to the seperation by the pericardial cavity, it is not condiered a layer of the heart
• Pericardial layers
  
  • Visceral layer of serous pericardium (epicardium)
    
    • Pericardial cavity:
      
      • space between the visceral and parietal layers of the serous pericardium that contains serous, pericardial fluid
  • 1- Serous pericardium (innermost)
  • 2- Parietal layer of serous pericardium: Fibrous pericardium (outermost)

Septums:

• Interventricular septum
  
  • Composed of:
    
    • Membranous septum:
      
      • Consists of tough collagenous fibrous connective tissue
      • serve as an attachment for some cardiac muscle fibers.
    • Myocardial septum:
      
      • Located in the lower part of the interventricular septum
      • Continuous with the myocardium of the heart,
      • Covered on both sides by the endocardium.
      • The membranous septum c, lying on the upper part of the interventricular septum. This constitutes
• Interatrial septum ????????
  
  • thinner
  • center layer of cardial muscle (EXCEPT fibrous area?)
  • lined by endothelium

​————————

Skeleton:

• The cardiac skeleton is made of dense fibrous ligament, to which the myocardium is attached together with all the valves .
• Separates the atrial myocardium from the ventricular myocardium
  
  • ​(the only link between the atrial myocardium and the ventricular myocardium is the so-called His bundle passing through the trigonum fibrosum dextrum).
• Structure:
  
  • 4 fibrous rings, dense irregular CT
  • supporting heart valves, cardiomyocytes and electrical isolation of atrial from ventricles
• Cardiac valves:
  
  • Atrioventricular valves= the tricuspid and mitral
    
    • Atrial side: (superficial to deep)
      
      • Endothelium
      • Thick layer of elastic connective tissue
        
        • Composed of elastic fibers and fibroblasts.
    • Ventral side: (deep to superfical)
      
      • 1- Plate of dense fibrous connective tissue
        
        • Bundles of collagen fibers and a small amount of fibroblasts.
        • This dense connective tissue is penetrated by the fibrous chordae tendineae
          
          • Fibrous thread like chords also covered woth endothelium
          • Which connect the valve flaps to the papillary muscles of the ventricles.
          • The core of the chordae tendineae is composed of bundles of collagen fibers parallel to the long axis, with scattered fibroblasts.
          • The surface of chordae tendineae is invested by a layer of endothelium.
      • 2- Endothelium
• The inner surface of the ventricle also contains prominent muscular (myocardial) ridges called trabeculae carneae (10) that give rise to the papillary muscles (11).
  
  • The papillary muscles (11) via the chorda tendineae (8) hold and stabilize the cusps in the atrioventricular valves of the right and left ventricles during ventricular contractions

Conducting system of the heart

• Contraction of heart are without direct stimulous of nervous system
• Special cardiomyocytes:
  
  • Capable of producing and conducting a stimulus nesseary for initiation of cardiac activity: myocardial contraction
  • Staining: Less epsinophillic than working cardiomyocytes, myofibirls only viable a the end
  • Contain more glycogen around ncl
  • Connections by desmosomes and gap junction, no intercalated discs
• Contraction cycle
  
  • Initiated from atria→
    
    • SA (sinoatrial node)= pacemaker of heart
      
      • near junction of SVC and right atrium →
    • AV node (atrioventicular)
      
      • impulse from SA picked up here→
      • AV bunddle of HIS:
        
        • specilized cardiac mucle cells, larger than nodes
        • carries across fibrous skeleton to ventricles →
      • Right and Left branches→
      • Subendothelial branchs,
        
        • AKA purkinjie fibers
        • round ncl. and larger than cardiac msucle
          
          • intercalated discs apprent, byt variable in apperance and number
          • PAS possitive (large amount of glycogen)

size 50*150μm, voluminous sarcoplasm rich in glycogen, numerous gap junctions - fast conduction, isolated from surrounding myocardium by connective tissue

WTF

Regeneration of the myocardium

• Regeneration is limited – eg. Myocardial infarction – healing through fibrous scar

From a histological perspective, the interatrial conduction pathway is a series of parallel strands of myocardium traveling in the subepicardiac layer. The myocytes within Bachmann’s bundle are encased in thin septa made of tightly packed collagen fibrils. This uninterrupted sheath also forms inter-septal connections (the function of which is not yet clear). There are five identified cell types found within the interatrial pathway. These are:

Myofibril-rich cells – which are the same as regular cardiomyocytes.

Myofibril-poor cells – resemble Purkinje cells; are numerous in the pathway.

P cells – like those described in the sinuatrial node.

Slender transitional cells – short and narrow.

Broad transitional cells – longer and wider than slender transitional cells.

The presence of these specialized cells facilitates rapid conduction of the action potential across the left atrium, minimizing the delay in depolarization between the atria. Bachmann’s bundle receives its blood supply from the sinuatrial nodal branch of the coronary artery.

Physiology of the conducting system

Conduction speed:

• SA – 50-70 impulses/min
• Atrial myocardium 0,5m/s
• AV node 0,05m/s
• Bundle of His and bundle branches 1m/s Purkynje fibers 3m/s
• Working myocardium 1m/s

Variable morphology and different connexin molecules

• AV node connexin 45, Purkynje fibers connexin 40, working myocardium connexin 43

Question 6

Overview of the immune system

Cell-mediated immunity

• Handles intracellular pathogens.
• Once a cell has been exposed to the microbe, the antigen can be reflected on the cell surface (i.e. antigen presenting cells).
• T lymphocytes are able to bind to major histocompatibility complexes (MHCs) that are found on all cell surfaces.
  
  • Types of MHCs
  • Type 1 and type 2.
  • MHC I molecules
    
    • Found on all nucleated cells in the body as well as platelets.
    • They are bound by CD8 positive T lymphocytes.
  • MHC II
    
    • Normally present on antigen presenting cells
      
      • Bound by CD4 positive T lymphocytes.
      • The CD8 positive cells are also referred to as cytotoxic T lymphocytes; they bind to the antigen presenting cell and induce apoptosis.
    • Other antigen presenting cells present in the circulation include the previously discussed dendritic cells, follicular dendritic cells in the lymph nodes, and macrophages.
    • Of note, there are also regulatory T lymphocytes that downregulate the proliferation of more T lymphocytes when necessary.

Answer 6

OPENING:

• Immune system=
  
  • Consists of groups of cells, tissues, and organs
    
    • That monitor body surfaces and internal fluid compartments and react to the presence of potentially harmful substances.
      
      • Prevents negative effects of antigens (bacteria, viruses, products of tissue decomposition, foreing cells, proteins and other macromolecules).
• Included in this system are:
  
  • The diffuse lymphatic tissue,
  • lymphatic nodules,
  • lymph nodes,
  • spleen,
  • bone marrow,
  • thymus

Types of immunity

***All activities of the innate and adaptive immunity are coordinated by cytokines.

1- Innate (nonspecific):

• Composed of physical, chemical, cellular, and humoral defense mechanisms against pathogens.
• Present at birth and does not require imprinting or adaptation to specific antigens.
  
  • Also referred to as nonspecific immunity.
• Response to pathogens is rapid, occurring within minutes to hours of exposure.
• OVERVIEW:
  
  • physical barriers (skin, mucosas),
  • chemical defense (e.g. low pH),
  • secretions (lysozyme, defensisn, interferons, complement),
  • phagocyting cells
    
    • Macrophages
      
      • Monocytes that migrate into specific tissue are subsequently referred to as macrophages
      • Can also be seen in the absence of an infectious or inflammatory process
      • After macrophages engulf the invading microbes, they are able to present fragments of the pathogen’s protein on their surface= antigen presentation
    • Monocytes
      
      • ability of these cells to engulf and destroy the pathogens
      • develops from the common myeloid progenitor cells under the influence of granulocyte macrophage colony stimulating factor (GM-CSF).
      • myeloblasts→ monoblasts→ promonocytes →monocytes
    • neutrophils,
    • eosinophils),
  • NK cells.

2- Adaptive (specific):

• Provides an antigen-specific response
  
  • Following exposure to a microbial pathogen or foreign substance (e.g., antigen).
  • Initiates sequence of reactions involving activated cells of the immune system and produces memory lymphocytes.
• Involves
  
  • B cells, T cells, and circulating antibodies
  • all of which mount a targeted immune response to a particular antigen/invading pathogen.
• An important component of adaptive immunity is immunologic memory,
  
  • A mechanism by which the immune system forms memory B cells and memory T cells.
  • These cells are able to trigger a more rapid and extensive response following subsequent antigen exposure.
• ANAKDOTOT
  
  • Autoimmunity=
    
    • A disorder of the adaptive immune system and is characterized by immune responses to the body’s own tissue.
  • Immunodeficiency conditions,
    
    • in which a compromised immune system leaves the body highly susceptible to infections,
      
      • can be either congenital (see the learning card on congenital immunodeficiency disorders for more information)
      • or acquired (e.g., HIV infection, iatrogenic immunosuppression).
• Types of specific immunity
  
  • Humoral:
    
    • Antibody secretion that mark invaders for distruction,
    • Antobodies are produced by B lymphocytes and plasma cells
  • Cellular immune response:
    
    • mediated by T lymphocytes (cytotoxic “killer cells”)
    • destroying foreign, transformed or virus infected cells

Cells of addaptive immunity:

1. Antigen-presenting cells ,APC

• Recognize and bind foreign antigens
• Connects the innate and adaptive immune systems
  
  • Macrophages (lymph nodes)
  • Epithelial reticular cells in thymus
  • Specillized dendritic cells: (spleen, lymph nodes..)
    
    • phagocytosis, express MCH I (for all cells), signal centroblast diffrentiation
  • B-lymphocytes

MCH molecules:

• Major histocompatibility gene complex
• Display short fragments of digested protiens on surface of cell
  
  • I: on all nucleated cells and platlets
    
    • T8 cytotoxic T tymphocytes
  • II: expressed on surface of APC
    
    • present peptide to T helper, 4
      
      • ​B lymophocytes and NK

2. Lymphocytes

• T lymphocytes
  
  • Compleate differentiation in the thymus
  • Cell mediated immunity, antigen specific
    
    • can be activated by APC
  • 60-70% of lymphocytes
  • T cell receptors: TCRs
  • Classifications:
    
    • CD4+Helper
    • Production of cytokines:
      
      • promoting dfferentiation of plasma cells,
      • Activation of macrophages and cytotoxic cells;
    • Some of them persist as memory cells
    • Only recognize antigens when attched to MCH II molecule
    • CD8+: Cytotoxic T- cells
      
      • Kill target cells: virus/cancer/ parasite infected cells
        
        • similar to NK, but more specific
      • Only recognize antigens when attched to MCH I molecule
• Regulatory T- cells : (CD4+ CD25+)
  • Suppress excessive immune response, maintain unresposiveness to self antigens.

B lymphocytes

• Compleate differentiation in the bone marrow
• Involved in production and sectertion of antibodies- immuniglobulins (Ig)
  • assosiated with humoral immunity
• Don’t need MCH complex to bind to antigens
  
  • Once phagoctyosis, it can express the antigen on MCH II for T cells
  • Activation of T cell helps B cell to mature into plasma cell, that can secret antibodies (immunoglobulins)
  • Antibodies have the same specifity of the original B cell
    
    • C- cell receptor in a secreted form, can dirculate in the non cellular part of the blood- attaching to pathogens and marking them for distruction- hemoral immunity
• Some of them remain as long - lived memory cells.
• Maturation:
  
  • formed in bone marrow (during lymphopiesis)- naive B cell
  • travel to peripheral lymph organ to encounter antigens
    
    • old antigen: will be transormed to plasmoblast, miargate to marginal zone of lymph nodule, and give rise to plasmocytes
    • new:

immunoglobulins (antibodies) produced by plasma cells

• Humoral response:
• IgA –
  
  • found in exocrine secretions (milk, saliva, tears, mucus),
  • prevents the proliferation of mikroorganisms
• IgE –
  
  • bound to receptors of mast cells and basophils, its complex with antigen triggers the liberation of histamine, heparin, leukotrienes.
• IgD –
  
  • acts as antigen receptor (together with the IgM) in triggering B-cell activation
• IgG –
  
  • represents 75%-85% of immunoglobulin in the blood, crosses the placental barrier;
  • complement activation, opsonization of microorganisms
• IgM – complement activation, antigen receptor

NK cells

• Compleate differentiation in the bone marrow
• Large lymphocytes with granules
• kill target cells: cancer/ virus cells?
• release cytotoxic granules dirrectly in the target cell
• 5-10%
• innate immune system?

​———————–

GO OVER IN GENERAL

EXAMPLES INNATE

1- Physical, chemical, and biological mechanisms

• Intact outer skin and mucous membranes (physical barrier)
  
  • Tight junctions between epithelial cells
  • Ciliary function of the respiratory tract
  • Normal flora (commensal microorganisms): harmless microorganisms that protect against pathogens
    
    • Imbalances in natural flora can lead to various diseases: e.g., oral thrush, bacterial vaginosis, pseudomembranous colitis
• Mucus (chemical barrier) contains nonspecific and specific protective substances against infection.
  
  • Lysozyme: enzyme formed from neutrophils, granulocytes, and macrophages that can lyse linkages in peptidoglycans
  • Lactoferrin: exhibits enzyme‑like properties and binds iron
  • Immunoglobulins: (particularly IgA) bridge the innate and adaptive immune responses
• Coughing and sneezing (reflex) protect airways
• Defensins
  
  • An antimicrobial peptide secreted by Paneth cells of the small intestine as part of the innate immune response.
• Exocytosis of cytotoxic molecules and proteins
  
  • Major basic protein: produced by eosinophils in response to antibody-dependent processes (IgE, antibody-dependent cell-mediated cytotoxicity) and important in the defense against helminthic infections.
  • IgE coat pathogens; major basic protein
  • Toxic products of respiratory burst:
    
    • ​Definition: generation of reactive oxygen species (free radicals) in phagocytes (e.g., neutrophils, monocytes) for the destruction of ingested pathogens in phagosomes
• 2- Cells
  
  • Granulocytes
  • Neutrophils
  • Eosinophils
  • Basophils
  • Mast cells
  • Antigen-presenting cells
  • Mononuclear phagocyte system
  • Dendritic cells
  • B cells

=

• Initial reaction: inflamation- non specific defense
  • Neutrophils: physiclly digest it with enzymes
  • Macrophage: phagocytosis
    
    • can lead to presentation of antigen- causing specific immune resposne

​

Development- classification of lymph organs

• Primary (central) lymphatic organ
  
  • bone marrow, GALT, thymus
  • lymphocytes diffrentiate into immunocompenentcells in these organs
• Secondary lymphatic organs
  
  • Immunocompenent lymphocytes organize around reticular cells and fibers to form effector lymphatic tissue and organs:
  • Secondary (periphreal) lymph organs
    
    • Lymphatic nodules, lymph nodes, tonsils, spleen, MALT
      
      • ​MALT (tonsils, Peyer patches, appendix)
  • Programmed to recongize a single antigen: antigen- independent proliferation and diffrentiation

Question 7

Lymph node, structure and function

Secondary lymphatic organs

The secondary lymphatic organs are the spleen, lymph nodes, and mucosa-associated lymphatic tissue,e.g., the Peyer patches and tonsils. It is in the secondary lymphatic organs that antigen presentation occurs. They are also the site of differentiation of mature, naive lymphocytes into effector cells.

Answer 7

The lymphatic organs

• include the thymus, lymph nodes, tonsils, and spleen, and are involved in lymphocyte production, immune responses, or both.
• Lymphatic organs are composed of lymphatic tissue, aggregates of lymphocytes and macrophages
• Supported by a framework of reticular tissue, which is formed of reticular fibers and reticular cells.

Lymph node:

Kidney bean shaped lymphoid organ located in the circulation of lymphatic vessels

• Secondary lymphoid organ
  
  • In which immune cells interact with extrinsic antigens to generate an antigen-specific response.
• Function
  
  • Lymph filtration: macrophages within lymph node
  • Storage of B and T cells
  • Immune system activation:
    
    • Antigen presentation induces differentiation and proliferation of B lymphocytes
    • And activation of T lymphocytes.
• Location:
  
  • Throughout the body in close proximity to organs and large vessels
• Structure
  
  • Bean-shaped organ surrounded by fibrous capsule with trabeculae
  • Numerous afferent lymphatic vessels enter through the capsule.
  • The trabecular sinus leads lymph from the subcapsular sinus to the medullary sinus.
  • The hilus allows blood vessels and efferent lymphatic vessel to enter or leave the lymph node
  • The entering artery and vein branch into a large capillary network, which forms the post-capillary high endothelial venules.
• Function: biological filter of lymph
• • Lymph flow:
    
    • Afferent lymph vesseles: twards node
    • EF: away from node and leave the hilum
• armbit, groin, near large jugular vessels, abdominal cavity

Structure:

1- Capsule: dense CT

• Hilum:
  
  • Point of entry for
    
    • blood vessels
    • nerves,
    • EF lymph vessels
• Trabeculae: extened from capsule into substance of node

2- Stroma:

• Reticular CT (reticular cells: secrete collagen III)
• Dendritic cells:
  
  • bone marrow derived APC, monitor local enviorment for foreign substances and present to specific T cells (using MCH I and II)
  • Macrophages: phagocytotic and antigen presenting (MCH I, II), less efficent APC than dentritic cells. high endocytosis.
  • Follicular dentritic cells:
    
    • in gernimal center
    • multiple cytoplamsic processes that integrate between B cells
    • antogen-antibody complex adheres to dendritic cytoplasmic processes with Fc receptor )not APC)
• Sinus:
  
  • Spaces, where lymph from AF vessels flow, endothelial lining is not continous- Placment for filtration
  • The system of lymph sinuses consists of three parts:
    
    • subcapsular (marginal) sinus
      
      • the space between outer cortex and capsule;
    • intermediate (cortical) sinus
      
      • the space between cortical nodule and trabecula that separates the cortex into incomplete compartments;
    • medullary sinus
      
      • the space between medullary cords.
• Cortex: (B-cell zone):
  
  • located directly inder the capsul and the marginal sinus
  • Lymphocytes organized into primary/secondary nodules
    
    • ​Lymphoid follicles: site of B lymphocyte storage, differentiation, and proliferation
    • Primary follicle (inactive): aggregates of naive B lymphocytes, basophillic nucleus and condensed chromatin
    • Secondary follicle (active): dense mantle zone surrounding a pale germinal center
• ​Paracortex (T-cell zone) :​
  
  • T lymphocytes and high endothelial venules
    
    • Free of nodules
  • Site of T-cell activation
• Medulla
  
  • Inner most part of lymph node,
    
    • Between paracortical zone and hilum
  • Lymphatic tissue: medullary chords seperrated by medullary sinuses
    
    • Medullary cords: mainly B cells, macrophages, dendritic, plasma
    • Medullary sinuses drain into efferent lymphatic vessels
  • Reticular cells and fibers transvers the medullary chords and sinuses and forms the frame work for the parnechyma
• Anastomotic chords of lymphatic tissue?
  
  • High occurence of machrophages with phagocytosed material

EXTRA

Lymph nodules:

• Primary: without germinal centers, non activated
• Secondary
  
  • Active, lighter center
  • Germinal center:
    
    • develops when a lymphocyte as recongnized an antigen.
    • Follicular dendrtitic cells FDCs also present
      
      • Dark zone: proliferating centroblasms (densly clustered nuclei
      • Light zone: centrocytes
  • Mantel layer: outer ring, naive B lymphocytes
  • Marginal zone: plasmoblasts and memory cells
• Locations:
  
  • Tonsils
    
    • ring of lymphatic tissue in entrance of oropharynx
    • Pharyngeal tonsils: roof pharynx
    • Palatine tonsils: between palatopharyngeal arch and palatoglossus
      
      • in mucous membrane- on wall of tonsilar crypt
      • dont contain afferent lymph vessels
    • Lingual tonsil: base of tounge
  • Peypers patchs
    
    • in ileum
    • in additon there is single/ solitary lymph nodules along large and small intestines
  • Veriform appendix
    
    • Cecum
    • lamina proproa

Question 8

Thymus, structure and function

Answer 8

General:

• Primary lymphoid organs in superior mediastinum, Retrosternal
  
  • A lymphoid organ that generates mature lymphocytes from immature progenitor cells.
• Function:
  
  • maturation and differentiation of T lymphocytes
• Develops from the endoderm of the 3rd pharyngeal pouch
  
  • Precursors of lymphocytes originating in the bone marrow migrate there from the 9th week of pregnancy.
  • Fully formed and functional at birth
    
    • Large organ until puperty
    • After:
      
      • T cells diffrentiation and proliferation are reduced and most lymphatic tissue is replaced by adipose tissue
      • AKA: Involution of the thymus
        
        • Thining of the cortex
        • Enlargement of Hassall corpuscles (aggregates of stromal epithelial cells)
        • Replacement of active tissue by adipose tissue.
    • Organ can be restimulated under conditions that demand rapid T cell proliferation

Structure:

• Left and right lobe
• Fibrous capsule
  
  • Fibrous septum/trabeculae that
    
    • Incomplete septa (s)
      
      • Establish lobules
      • Contain arteries branching into cortical capillaries, venules are of HEVs type.
      • The capsule, septa and vessels are insulated from lymphocytes by epithelial stromal cells (blood-thymus barrier).
• Cortex
  
  • Cortex
    
    • Dark, densely packed, immature T lymphocytes (thymocytes)
      
      • Closly packed developing T- Lymphocytes with intensly stained nuclei (AKA thomocytes); Basophillic
      • Mitoticlly active and immature, more in periphery
      • Lymphocytes gradually mature twards corticomedullary junction
    • Macrophages: phagocytosis of cells that dont meet requirenmts
    • ​Meshwork of reticular epithlium
      
      • ​​Cover the blood vessles with their processes: forming barrier
• Medulla
  
  • Light, fewer cells; Mature T lymphocytes and Hassall corpuscles
  • Epithelioreticular cells
    
    • Do not fully cover the blood vessels, no barrier is needed due to the fact that T cells already encountered antigen
      
      • Thought to produce inerleukins: function in diffrentiation and education of T cells
      • Contain keratohyalin granules, IF, lipid droplets and joined. by desmosomes
  • Hassels corpusles (VI)
    
    • oval structures consisting of round or spherical aggregations (whorls) of flattened epithelial cells.
      
      • VI reticular epithlium
    • The thymic corpuscles also exhibit calcification or degeneration centers that stain pink or eosinophilic. The functional significance of these corpuscles remains unknown.

Blood- Thumus barrier

• Physical barrier
• Protects the proliferation and maturation of thymocytes from exposure to antigens
  
  • Endothelium lining capillary wall:
    
    • occulding junctions
  • Basal lamina of endothelial cells and occasional pericytes
  • Perivascular compartment:
    
    • containing machrophages
  • Type I epithelioreticular cells+basal lamina
    
    • containing occluding junctions
    • in cortex

T cell development

• T cells originate from lymphoid progenitor cells in the bone marrow and mature in the thymus (hence “T cells”).
• The thymus is a primary lymphatic organ that arises from the ventral wings of the third branchial pouches.
  
  • The thymus grows during childhood after which it begins to atrophy (thymic involution).
  • In young children, thoracic x-ray normally shows a prominent thymic shadow.
• Positive selection of T cells ensures that the thymus produces functional T cells.
  
  • Takes place in the thymic cortex
    
    • Dense, peripheral region of the thymus
    • Predominantly contains immature T cells
  • Thymic cortical cells express MHC class I and MHC class II antigens.
    
    • Tests if T-cell receptors can bind MHC appropriately (not too strongly or too weakly)
      
      • T cells (CD4+ / CD8+) receive survival signal.
      • Dysfunctional T cells then undergo apoptosis.
  • Negative selection of T cells ensures that the thymus does not produce self-reacting T cells.
    
    • Takes place in the thymic medulla
      
      • Central, pale region of the thymus
      • Predominantly contains mature T cells
    • Tests if T cells bind to tissue-restricted self-antigens presented on MHC by thymic medullary cells
      
      • T cells that do not bind receive survival signal.
      • Dysfunctional T cells undergo apoptosis.
        
        • Mediated by the autoimmune regulator protein (AIRE)
• Additionally, T cells bind with their cluster of differentiation (CD).
  
  • The type of CD that the T cell has a higher affinity for is kept while the other is downregulated to either (CD4+ / CD8-) or (CD4- / CD8+).
    
    • CD4 binds to MHC II
    • CD8 binds to MHC I

Immunocompetent (but still naive) T cells leave the thymus and migrate within and between peripheral tissues, blood vessels, and secondary lymphoid organs (e.g., lymph nodes, spleen, MALT).

Question 9

Spleen, structure and function

Answer 9

OPENING:

• The spleen is a fist sized organ located in the left upper quadrant of the abdomen.
• It is the largest lymphoid organ and thus the largest filter of blood in the human body.
• The spleen has a unique location, embryological development and histological structure that differs significantly from other lymphoid organs.
• Functions:
  
  • Filtering blood
  • Maintaining immune response
  • Balance and recycling iron.
  • Reservoir for additional blood in situations of acute or chronic blood loss (such as bleeding or anemia),
  • As well as an alternative site for hematopoiesis (formation of blood cells and platelets) outside of bone marrow.
  • Even though the spleen has a few unique functions that can’t be replaced by other lymphoid organs, it is not a vital organ and people can live without it.
• filters blood anf recats immunologiclly to blood bonre antigens

Strucutre

• Tunica serosa
  
  • Being an intraperitoneal organ, the spleen is covered by a layer of visceral peritoneum.
    
    • Loose CT and mesothelium

Underneath the peritoneum is the capsule of the spleen, encasing its parenchyma.

• Capsule/ tunica fibrosa
  
  • Dense irregular connective tissue with myofibroblasts
    
    • contractile cells:
      
      • Help to discharge the blood stored within the spleen into the circulation.
      • Also allows the spleen to significantly increase in size when necessary and discharge a large amount of blood to contribute to the tissues oxygenation, like during physical exercise.
  • Hilium: entry site of arteries and nerves, exit of viens and efferent lymph
  • Trabeculae splinae
    
    • Columnar projections from capsule, do not branch
    • Penetrate into the parenchyma of the spleen and partly divide its tissue, accompanied by arteries
    • Contain myofibroblasts
      
      • contractile cells producing extracellular CT fibers

Stroma of the spleen

• is composed mainly of a network of reticular connective tissue.
• This mesh provides support for blood cells and cells of the immune system (lymphocytes, macrophages, and dendritic cells).

Parenchyma of the spleen

• Is divided into two functionally and morphologically distinct compartments
  
  • Red pulp and white pulp
• Divided by a tissue layer called the marginal zone.
  
  • Outside the marginal zone is the perifollicular zone which contains sheathed capillaries and blood-filled spaces without endothelial lining.
• White splenic pulp: (25%)
  
  • Periarteriolar lymphatic sheath (PALS)
    
    • Surrounds the arterioles
    • Dense lymphoid tissue containing T lymphocytes
    • Branchs of splenic artery enter white pulp → when inside them called central artery → lymphocytes aggrigate around the central artery- PALS
      
      • Thymus dependent zone
      • Can respmble a lymphatic nodule, not to be confused!
  • Follicles
    
    • Main component of white pulp, splenic nodules
      
      • Lymph nodule- teritory of B cells
      • Germinal centers
    • Close to PALS
    • Contain B lymphocytes
    • Most nodules found in the spleen are secondary nodules that arise from primary follicles as the lymphocytes mature and increase in size.
      
      • They differ from primary follicles by featuring a distinctive centrally positioned zone called the germinal center.
      • The germinal centers are the sites where lymphocytes mature and acquire the ability to produce antibodies.
      • So, seeing the germinal center is a sign that lymphatic tissue is responding to an antigen.
      • Other than B lymphocytes, the germinal centers also contain follicular dendritic cells (FDC) which also increase in number after antigen activation. They support B lymphocytes, initiate and modulate their immune response.
  • Marginal zone
    
    • Located between the red pulp and white pulp
    • Contains antigen-presenting cells (APCs):
      
      • Higher amount of macrophages and dendritic cells and the expense of lymphocytes

basophillic: dense herterochormatin in nuclei

• Red pulp (75%)
  
  • Majority of the stromal tissue of the spleen.
  • Spleen sinusoids:
    
    • Fenestrated vessels that prevent old or malformed RBCs/platelets from re-entering venous circulation
    • special sinusoidal vessels lined by rod shape endothelial cells
    • Dont contain continuous basal lamina
    • staines with silver impregnamtion or PAS
    • Intercellular spaces that allow blood to pass in and out process of macrophages extened between the spaces to monitor passing
  • The cords of Billroth (splenic cords)
    
    • Cellular aggregations supported by the reticular connective tissue.
    • They appear as stripes and consist of macrophages, plasmocytes and blood cells.
      
      • Filled with blood and give the red pulp its distinguishable red appearance.
      • Macrophage- phagocytosis dammaged RBC, and begin the breakdown of hemoglobin and iorn reclamation.
    • Blood slowly flows through the sinusoids→ where it is exposed to macrophages from the cords of Billroth→ patiently waiting for foreign antigens that can appear in the blood.
      
      • Functions as a blood filter for various toxins, destroying them before they enter systemic circulation and get the chance to spread throughout the body and damage other organs.

​————————–

Vascular supply: open circulation

• exposes blood more efficiently to machrophages in red pulp
• splenic artery→
• central artery→ ​
  
  • Branchs to
  • white pulp
  • marginal sinuses of white pulp
  • central artery coninues to→
• Red pulp→ penicilliar arterioles→ continue as atrieal capillaries
• Some of these capilaries are surrounded by marcophages:
  
  • These capillaries are surrounded by clusters of macrophages and are called sheathed capillaries​
• sheathed capilaries empty into reticular mesh of splenic chords→ exposing to more machrophages goes to splenic sinuses
• From this point on, blood travels freely through the venous sinuses of the red pulp.
• The endothelial cells of the sinusoids have special histological features; they are elongated, spindle-shaped and don’t have characteristic cellular junctions to adjacent cells.
• From the maze made of venous sinuses, the blood flows into trabecular veins and eventually exits the spleen through the splenic vein.

——-

EXTRA:

Functions

• One of the most important functions of the spleen is blood filtering. It is considered a “graveyard for red blood cells” because it removes old and damaged erythrocytes from circulation. This function is mostly due to the unique structure of the blood vessels and macrophages present in the red pulp. The macrophages phagocyte and destroy erythrocytes and then recycle their iron from hemoglobin. Eventually, iron ends up stored and reused in bone marrow.
• Despite being the best-known destroyer of blood cells, the spleen can also be a site of their production. During fetal development, before bone marrow fully develops, the spleen is an important site of hematopoiesis. After birth, blood is produced in the spleen only during some pathological conditions such as severe bacterial infections. The spleen also stores a certain amount of blood in its blood vessels that can be released in a state of acute and severe blood loss.
• Being the largest lymphoid organ, the spleen is one of the major sites of initiating and modulating the immune response. It can detect and present specific pathogens in the blood and produce an immune response to defend the body against them. The specific structure of the spleen makes it a key spot for defense against encapsulated bacteria. This is why people without a spleen are predisposed for some bacterial infections like pneumonia.