Histology Flashcards

1
Q

What cells are present in cartilage?

A

Chondroblasts and chondrocytes

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2
Q

What is the cartilage matrix?

A

hydrophilic condroitin sulphate-rich amorphous jelly, compressible - made up of glycoaminoglycans (GAGS)

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3
Q

Describe hyaline cartilage?

A

joints - glassy amorphous matrix

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4
Q

Describe elastic cartilage?

A

(similar structure to hyaline and fibrous): pinna of ear and epiglottis -visible elastic fibres within matrix. Able to spring back to its original shape more
easily than other types of cartilage

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5
Q

Describe fibrous cartilage?

A

intervertebral discs - visible collagen fibres within the matrix. Collagen fibres
are arranged in order, parallel to each other > gives extra strength

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6
Q

What cells are present in bone and what are their roles?

A

Osteoblasts: actively synthesise bone
• Osteocytes: maintain bone & regulate calcium levels
• Osteoclasts: break down bone and aid in remodelling bone [from a different stem
cell to that of osteoblasts & osteocytes]

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7
Q

What is present in the matrix of bone?

A
  • Organic: mostly collagen (type 1)

* Inorganic: calcium mostly in the form of crystalline hydroxyapatite

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8
Q

Describe simple squamous epithelium?

A

Single layer of flattened cells with parallel oval nucleus. They have a very thin cytoplasm, giving a large plate like cell, with a bulge where the nucleus is -plate like/fried egg in shape

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9
Q

Describe simple cuboidal epithelium?

A

single layer of cells, roughly square in profile, with a round nucleus. Found in the collecting ducts of kidneys and ducts of glands

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10
Q

Describe simple columnar epithelium?

A

Single layer of cells taller than wide with an oval, perpendicular nucleus.
Is the epithelium that lines the inside of the intestines, gall bladder
and some airways (bronchus). Microvilli or cilia may be present.

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11
Q

Describe Stratified Squamous Non-Keratinised Epithelium?

A

found in the mouth, oropharynx, oesophagus & vagina. Basement
membrane lies between epithelium & supportive connective tissue.

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12
Q

Describe Squamous Keratinised Epithelium?

A

Found on outside of body as hairy or non-hairy skin. Cells on surface of skin are dead, have no nuclei and are full of keratin

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13
Q

Describe Pseudostratified Epithelium?

A

stretchable, cells piled up on a basement membrane. Looks like layers of cells when actually there’s only one layer

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14
Q

What are microvilli?

A

regular finger-like projections from the apical surface of absorptive cells

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15
Q

What are cilia?

A

regular motile appendages on the apical surface of cells of parts of the respiratory and female reproductive tracts

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16
Q

What are adherent(tight) junctions?

A

band-like fusions between cells that are impervious to most molecules

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17
Q

What are desmosomes?

A

plaques that form physical joint between cells and

connect the cytoskeletons of adjacent cells

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18
Q

What are gap junctions?

A

Electrical junctions that permit the transfer of small molecules

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19
Q

Which collagen is present in the basement membrane?

A

Type IV

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20
Q

What are the three types of muscle?

A

Voluntary(skeletal) muscle, involuntary (smooth/visceral) muscle, and cardiac muscle

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21
Q

What are the three types of connective tissue?

A

Fibrous, Hard, and Fatty

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22
Q

Where would you find the core types of collagen?

A

Type 1: Skin, tendon, organs, and bone

Type II: cartilage

Type III: liver

Type IV:Basement membranes

Type V: Placenta

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23
Q

What is white fatty tissue?

A

large cells with single fat globule in
each cell. Usually appears empty (white) in slides
since fat is extracted during processing

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24
Q

What is brown fatty tissue?

A

Cells with many globules of fat. Found across shoulders and down back of newborn - important in neonatal-thermoregulation since they generate heat on breakdown

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25
Q

What are the features of the pulmonary circulation vessels?

A

The pulmonary circulation has to only transfer blood a short distance from the right ventricle of the heart to the capillary system of the lung , and from there back to the left atrium of the heart. Distances are short compared to those involved in the more complex systemic circulation , pressures within the pulmonary circulation are much lower and the vessel walls are generally thinner.

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26
Q

What are the three identifiable layers of blood vessels?

A

Intima, Media and Adeventitia

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27
Q

Describe the intima?

A

• The intima composed of aligning layer of highly specialised multi functional flat and epithelial cells termed endothelium.
• sits on a basal lamina; beneath this is a very thin subendothelial layer of fibro collagenous support tissue containing occasional contractile cells with some of the properties of smooth muscle cells but which are also capable of synthesising collagen and elastin and which can also have phagocytic properties.
these cells are called myointimal cells and become very important in the development of the most common arterial disease atheroma

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28
Q

Describe the media?

A

• the media is the middle layer in a blood vessel wall and is composed predominantly of smooth muscle reinforced by organised layers of elastic tissue which form elastic laminae
• the media is particularly prominent in arteries, being relatively indistinct in veins and virtually nonexistent in very small vessels
• in vessels that are close to the heart, receiving the full thrust of this systolic pressure wave, elastic tissue is very well developed hence the term elastic arteries
• in muscular arteries and arterials the prominent elastic lamina just below the intima is termed the internal elastic lamina
Media contains abundant concentric sheets of elastin

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29
Q

Describe the adventitia?

A
  • the outer layer of blood vessels. It is composed largely of collagen but smooth muscle cells may be present particularly in veins.
    • often the most prominent layer in the walls of veins
    • Within the adventitia of vessels with thick walls are small blood vessels the vasa vasorum which send penetrating branches into the media to supply it with blood. these are not seen in thinner vessels, which obtain their oxygen by diffusion from the lumen
    • carries autonomic nerves which innervates the smooth muscle of the media
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30
Q

What is the endothelium?

A

The endothelium is highly specialised, with endocrine, exocrine, cell adhesion, clotting and transport functions

• In routine histologically sections the cytoplasm of most endothelial cells is barely visible and only the small flat and nuclei are seen
• ultrastructurally, each cell can be seen to be anchored to an underlying basal lamina; individual cells are anchored together by adhesion junctions including prominent tight junctions which prevent diffusion between cells 
• a prominent feature of endothelial cells is the presence of many pinocytotic vesicles Which are involved in the process of transport of substances from one side of the cell to the other. In small blood vessels of the nervous system the endothelial cells expressed transport proteins, which are responsible for the active transport of all substances into the brain 
• Ultrastructurally, and the fuel cells also contain smooth and rough endoplasmic reticulum and free ribosome's with occasional mitochondria and variable numbers of microfilaments. the characteristic cytoplasm organelle of the endothelial cell is an electron dense ovoid structure called the Weibel-Palade body 
• endothelial cells are able to send changes in blood pressure oxygen tension and blood flow by as yet unknown mechanisms 
• in response to changes in local factors they respond by secreting substances which have powerful effects on the tone of vascular smooth muscle (endothelins, nitric oxide and prostacyclin, PGI2). Substances that cause relaxation of vascular smooth muscle increased local blood flow by causing vasodilation.
• endothelial cells important for control of blood coagulation and under normal circumstances the individual surface prevents blood clotting. This is done by high expression of factors that prevent blood clotting and low expression of factors that activate this process
• cells are bound together by junctional complexes and have many pinocytotic vesicles
• Cells have many functional roles despite their apparent structural simplicity 
• normally secretes factors which prevent blood clotting 
• normally secretes factors which maintain the tone of vascular smooth muscle  can be activated by cytokines to express cell adhesion molecules which allow white blood cells to stick
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31
Q

What are elastic arteries? And what is their structure?

A

• elastic arteries are characterised by multiple elastic laminae in the media
• elastic arteries are the largest arteries and receive the main output from the left ventricle thus they are subjected to the high systolic pressures of 120-160 mmHg
• these large vessels are adapted to smooth out the surges in blood flow
• the elastic tissue in their walls provides the resilience to smooth out the pressure wave
• the intima of large elastic arteries is composed of endothelium with a thin layer of underlying fibro collagenous tissue
• elastic arteries have a thick highly developed media of which elastic fibres are an important component. These are arranged in circumferential sheets between the layers of smooth muscle fibres throughout the thickness of the media. in the largest artery the aorta there are often 50 or more layers
• elastic fibres are arranged so that they run circumferentially rather than longitudinally in order to counteract the tendency of the vessel to over distend during systole
• Return of the elastic fibres from the stretched to the UN stretched state during diastole maintains a diastolic pressure within the author and large arteries of about 60-80mmHg
• interposed between the elastic layers are smooth muscle cells and some collagen
the adventitia of the large vessels carries vasa vasorum and nerves

examples include large arteries near the heart and the pulmonary arteries

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32
Q

What are muscular arteries? and what is their structure?

A
  • Media comprises layers of smooth muscle
    • Little elastin in the media
    • E.g. Radial artery
    • Splenic artery
    • Although they are muscular, elastin sheets are still present
    • Further away from the heart, vessels get smaller
    • muscular arteries have a media composed almost entirely of smooth muscle
    • Large elastic arteries gradually merge into muscular arteries by losing most of their medial elastic sheets usually leaving only two layers an internal elastic lamina and an external elastic lamina at the junction of the media with the intima and the adventitia
    • these arteries are highly contractile
    • that degree of contraction or relaxation being controlled by the autonomic nervous system as well as by endothelium derived vasoactive substances
    • note that a few fine elastic fibres are scattered among the smooth muscle cells but I’m not organised into sheets
    • muscular arteries vary in size from about 1 centimetre in diameter close to their origin at the elastic arteries to about 0.5 millimetres in diameter. in the larger arteries there may be 30 or more layers of smooth muscle cells whereas in the smallest peripheral arteries there are only two or three layers the smooth muscle cells are usually arranged circumferentially at right angles to the long axis of the vessel
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33
Q

What are arterioles and what is their structure?

A
  • Resistance vessels
    • Arbitrarily defined as having 3 or fewer muscle layers in their media
    • Up to 100 microns
    • Elastic laminae poorly defined
    • arterioles are the smallest branches of the arterial tree:
    • range from 30 micrometres to 400 micrometres
    • intima composed of endothelial cells lying on a basement membrane with an underlying fine internal elastic lamina in the larger arterioles
    • The arteriolar media is composed of one or two layers of smooth muscle cells. as the arterials become smaller the continuous layers of smooth muscle become progressively discontinuous in the smallest arterials the endothelial cells have basal processes which pierced the basement membrane and make junctional Contacts with the smooth muscle cells
    • adventitia is insignificant
    • arterials are very responsive to vasoactive stimuli and make a major contribution to vascular resistance
    • the microvasculature starts at the level of the arterioles
    • it is composed of small diameter blood vessels with partly permeable thin walls that permit the transfer of some blood components of the tissues and vice versa. Most of this exchange between blood and tissues occurs in the extensive capillary network, the smallest arterioles (metarterioles) emptying into the capillar system. The capillary networks drain into the first components of the venous system, the venules
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34
Q

What are capillaries and what is their structure?

A

specialised for diffusion of substances across their wall:
• smallest vessels of the blood circulatory system 5 to 10 micrometre in diameter and form a complex interlinking network
• have the finished walls of all blood vessels and all the major sites of gaseous exchange, permitting the transfer of oxygen from blood to tissues, and carbon dioxide from tissues to blood. Fluids containing large molecules pass across the capillary wall in both directions
• the capillary wall is composed of endothelial cells, a basement membrane, and occasional scattered contractile cells called pericytes
• capillaries with continuous endothelium are the most common type
• Capillaries with fenestrated endothelium are seen most commonly in the gastrointestinal mucosa, endocrine glands and renal glomeruli. The endothelial cell cytoplasm is pierced by pores which extend through its full thickness. In some fenestrations there is a thin diaphragm which is thinner than the cell membrane
• To regulate size of capillaries, they must be changeable
• This is done by pericytes
• In some capilaries, vascular endothelia is incomplete, this creates windows for movement of material out of the capillaries and into the surrounding cells, these are fenestrated capillaries
• Composed entirely of thin walled endothelial cells with no surrounding muscle or connective tissue
• Most tissues have closed capillaries but some tissues e.g. Kidney and liver have more fenestrated ones

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35
Q

What are sinusoids? And what is their structure?

A

large-diameter channels with thin walls:
• Highly specialised vascular channels, called sinusoids, are seen in some organs such as the liver an spleen
• they are endothelia lined channels with a larger diameter than capillarys and discontinuous or absent basement membrane
• the endothelia cells are commonly highly fenestrated and there may be substantial gaps between the cells

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36
Q

What are venules? And what is their structure?

A
  • Capillaries drain into post-capillary venules, which are the smallest venules (10-25 micrometers in diameter). They resemble capillaries but contain more pericytes
    • Postcapillary venules drain into large collecting venules 20-50 micrometers in diameter, in which the pericyte layer becomes continous and surrounding collagen fibers appear
    • As the collecting venules become larger bore the pericytes are progressively replaced by smooth muscle cells, which form a layer one to two cells thick and a fibrocollagenous adventitia becomes identifiable; these are muscular venules and are 50-100 microns in diameter. Muscular venules drain into the smallest veins
    • Associated with arterioles
    • Thin walled
    • Contractile pericytes wrap around outside of endothelial cells and form a complete layer as venules get larger
    • Pericytes replaced by smooth muscle as venules become veins
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37
Q

What are veins and what is their structure?

A
  • have thin walls and carry blood at low pressure:
    • vary in size from less than one millimetre to 4 centimetres in diameter. in comparison with arteries of comparable external diameter, veins have a larger lumen and a relatively thinner wall, and are therefore commonly collapsed in histological sections
    • small veins are a continuation of the muscular venules and have a similar wall structure but are larger with more clearly defined muscle cell and outer fibro collagenous tissue
    • medium sized veins of 1 to 10 millimetres in diameter. they have a inner layer of endothelial cells on a basement membrane. This is separated by a narrow zone of collagen fibres from an indistinct condensation of elastic fibres producing a thin discontinuous internal elastic lamina. the inner layer is fairly consistent in structure, differing only in quantity of collagen and elastic fibres between the endothelium and the condensation of elastic fibres. The outer layers vary considerably in thickness proportion of collagen, elastic fibres and smooth muscle and in the orientation of the muscle fibres in particular
    • large veins have an inner layer similar to that of medium sized veins but there are usually more collagen and elastic fibres between the endothelial basement membrane and the elastic lamina which is generally discontinuous. external to the elastic lamina there is a layer of smooth muscle imbedded in collagen and outside this is a thick layer of collagen in which there are bundles of longitudinally oriented smooth muscle fibres some elastic fibres do intermingle with the collagen
    • Valves in enlarged veins assist the flow of blood to the heart
    • venous circulation of blood is maintained by the contraction of venous smooth muscle, supplemented to varying degrees by external pressure from the contraction of the surrounding skeletal muscle responsible for arm and leg movement
    • the veins in the arms and legs, which carry blood against gravity are equipped with these valves to prevent blood flowing back down the vein. These valves are thin flaps of intima that project into the lumen, the free edges of the valve flaps pointing towards the heart: this allows blood to flow through the heart but prevents back flow. Incompetence of the valves in the veins of the legs causes varicose veins
    • valves are also present in other medium and large veins their number depending on whether or not the vein is carrying blood against gravity
    • Only endothelium and basement membrane
    • In veins-lumen is larger, media is thinner, no external elastic lamina
    • Large veins are thick walled relative to venules
    • Thin walled compared to artery
    • Smooth muscle in wall may be circular or longitudinal
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38
Q

What are arteriovenus anastomoses and what is their structure?

A
  • allow blood to bypass capillary beds
    • As well as the microvasculature there are additional vessels that bypass the capillary bed allowing arterials to communicate directly with manuals these are arteriovenous anastomoses
    • at its arteriolar end, an arterial venous anastomosis is thick walled due to an abundant smooth muscle coat which is richly innervated
    • contraction is the thick muscle layer closes off the lumen of the anastomosis at its origin and divert blood into the capillary bed
    • relaxation opens up the lumen allowing blood to flow directly into of annual and thereby bypassing the capillary network
    • they are most common in certain regions such as the fingertips lips nose ears and toes
    • they are thought to play important role in the skins thermoregulatory function
    • closure of the anastomosis diverts blood into the extensive dermo capillary system and permits heat loss and opening of the vessel closes the capillary bed and conserves heat
    • in the fingertips there is a highly specialised type of arteriovenus anastomosis, the glomus body, which has a prominent arterial end (Sucquet-Hoyer canal) connecting directly to the venular end. the canal is surrounded by modified smooth muscle cells which are richly innervated by the autonomic nervous system
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39
Q

What is the efferent innervation of blood vessels?

A
  • Blood vessels that can significantly alter their lumen size by contraction and relaxation of their smooth muscle fibres have a major supply of adrenergic sympathetic fibres, stimulation of which causes muscle contraction and vasoconstriction
    • some blood vessels in skeletal muscle also have a cholinergic sympathetic innervation capable of producing vasodilation
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40
Q

What is the afferent innervation of blood vessels?

A
  • in certain areas blood vessels have an afferent innervation which provides information about the lumenal pressure (baroreceptive information) and blood gas (i.e. Carbon dioxide and oxygen) levels (chemoreceptive information). These are mainly located in the carotid sinuses, and in the region of the aortic arch, pulmonary artery and large veins entering the heart
    • Afrin fibres from the carotid sinus receptors travel in the glossopharyngeal nerve to the cardio respiratory centres in the brain stem
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41
Q

What is a portal system?

A
  • portal circulations are venous channels that connect one capillary system with another and do not depend on the central pumping action of the heart
    • the nature of portal connecting vessels varies from side to side for example the vessels of the hepatic portal system which connects capillaries in the intestines of the capillary like sinusoids in the liver are Venus in nature being small venules adjacent to the capillary bed and medium and large size of veins in between. in the other main portal system between the hypothalamus and the posterior pituitary the connecting vessels are large capillaries and venules
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42
Q

What are the features of lymphatics?

A

• Thin walled, similar to capillaries and veins
Have valves
• Do not contain blood
• Contains eosinophilic lymph and may contain lymphocytes
• Lymphocytes tend to travel in the blood (worth noting)
• Note that the lumen contains protein rich lymph scattered with lymphocytes, thin media, thin adventitia
• the lymphatic system carries fluids that drains from the intercellular space of tissues:
• The intercellular spaces of almost all tissues contain small endothelial line tubes which are blind ending but otherwise identical in structure to blood capillaries. these are lymphatic pillories not permeable to fluids and dissolved molecules in the interstitial fluid
• in some areas the lymphatic capillaries have a fenestrated endothelium and a discontinuous basement membrane
• The lymphatic capillary network acts as a drainage system , removing surplus fluid from tissue spaces. Lymph is normally a clear colourless fluid , but lymph draining the intestine during absorption is often Milky in appearance because of its high lipid content, this is called chyle
• the lymphatic capillarys merge to form thicker walled vessels which resemble venules and medium sized veins
• lymph moves sluggishly from the capillary network into the larger lymphatic vessels back flow is prevented by numerous flap like valves similar to those in veins
• on its way to the largest vein like lymphatics from the smaller lymphatics lymph passes through one or more lymph nodes. he answers the lymph node at its convex periphery and leaves it through one or two lymphatic vessels at the concave hilum. during this passage any antigens in the lymph can be processed by the immune system. activated lymphocytes which are important to immune defence are added to the lymph
• the larger lymphatic vessels have muscular walls and pump the lymph into the following two main lymphatic vessels:
○ the thoracic duct- empties limp into the venous system at the junction of left internal jugular and left subclavian veins
○ the right main lymphatic duct- empties into the junction between the right internal jugular and right subclavian veins

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43
Q

What is plasma?

A

Plasma is blood minus all of the cells and comprises:
• Water
• Salts and minerals
• Plasma proteins (albumins, globulins, fibrinogen)
• Hormones, signal molecules
• Other clotting factors
Serum is plasma minus clotting factors

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44
Q

Describe the structure of bone marrow?

A

• Occupies the space between the trabeculae of medullary bone and consists of highly branched vascular sinuses and a reticulin scaffolding, with the interstices packed with hemopoietic cells
• Contains fixed macrophagic cells which remove aged and defective red cells from the circulation by phagocytosis. It also plays a central role in the immune system as it is the site of B lymphocyte maturation
• Outside the endothelium and basement membrane of the marrow sinusoids is a discontinuous layer of fibroblast like support cells known as reticular cells that synthesise collagenous reticulin fibres, extracellular matrix materials, and certain growth factors
by accumulating lipid the reticular support cells may transform into the adipocyte found in bone marrow

45
Q

What cell type do basophils, neutrophils, and eosinophils all come from?

A

Myeloblasts

46
Q

Describe erythropoiesis?

A

• Reducing cell size
• Haemoglobin production
• Reduction and loss of organelles
• Basophilia in early precursors changes to eosinophilia in late precursors
• Loss of nucleus
• Mediated by erythropoetin (EPO)
• red cells are the terminal differentiated progeny of 1 cell line of pluripotent bone marrow stem cells which is committed to erythropoesis only
• CFU-GEMM Cells give rise to progenitor cells that form bursts of erythroids cells in culture and these give rise to cells responsive to the growth factor erythropoietin
• Differentiation of these stem cells into mature red cells is associated with:
○ Decreasing cell size
○ Haemoglobin production
○ Gradual decrease and eventual loss of all cell organelles
○ Changing cytoplasmic staining, from intense basophilia due to large number of polyribosomes to eosinophilia due to haemoglobin
○ Condensation and eventual extrusion of the nucleus
• Along the path of red cell differentiation, certain morphologic cell types can be distinguished in routine marrow smears: proerythroblasts , basophilic erythroblast, polychromatic erythroblast, orthochromatic erythroblast and reticulocyte
• Red cells are formed in smaller erythroblastic islands insisting of one or two specialised macrophage is surrounded by bread so progenitor cells. the macrophage is have long cited plasma processes and deep invaginations to accommodate the dividing erythroid cells, which migrate outwards along the cyto plasmic process as they differentiate
• when mature the red cell Contacts nearby sinusoidal and the filium and passes out to enter the circulation
the term erythron describe the whole mass of mature red cells and their progenitors. it functions as a dispersed organ, the number of red cells and circulating blood being regulated to meet oxygen carrying needs, and the rate of red cell production varying with changing rates of their removal from the circulation . this behaviour is mediated by a number of factors but particularly by the growth factor erythropoeitin, whcih adjusts red cell production to match oxygen demand. Erythropoietin is secreted mainly by the kidneys in adults by the liver in the fetus

47
Q

Describe granulopoiesis?

A

• Morphology similar to neutrophils, eosinophils, and basophils
• Increasing number of granules
• Increasingly complex shape of the nucleus
• Large pool of stored mature neutrophils in marrow
• Pool can be mobilised rapidly when there is a disease process
• Eosinophils are derived from CFU-Eo progenitor cells under the influence of cytokines. Eosinophil myeloblasts resemble neutrophil myeloblasts, and there are comparable subsequent development stages. Eosinophils are readily distinguishable from neutrophils at the early myelocyte stage by the appearance of their larger granules, most of which are eosinophilic, but a few are initially basophilic.
• Basophils are formed from CFU-B progenitor cells. Basophil myeloblasts resemble neutrophil myeloblasts; development then proceeds through analogous stags to those of neutrophils and eosinophils. Basophil granules are distinguishable at the early myelocyte stage
• Monocytes leave the marrow soon after formation with no marrow pool
• The bone marrow is the site of formation of primitive lymphocuyte precursors which subsequently give rise to both T and B lymphocytes at different stages:
○ B cells undergo inititial maturation in the bone marrow and move on to colonise peripherial lymphoid tissues
○ T cells migrate to the thymus gland, where they undergo initial maturation before moving on to colonise peripheral lymphoid tissues
• Megakaryocytes are the largest cells seen in bone marrow aspirates, and produce platelets by cytoplasmic fragmentation
• The precursor of the megakaryocyte in bone marrow is the megakaryoblast, which duplicates its nuclear and cytoplasmic constituents up to seven times without cell division. Each causing increased ploidy, nuclear lobulation and cell size

48
Q

What is the pericardium?

A

Outer most layer of the heart
Layer of mesothelial cells resting on thin layer fibrous connective tissue
Single layer of squamous mesothelial cells
Visceral(outer surface) and parietal (layer of cells on inner surface)
The heart is enclosed within the pericardial sac, which is composed of compact fibro collagenous and elastic tissue and lined internally by a layer of flat mesothelial cells, termed the parietal pericardium. This smooth mesothelial layer reflects over the outer surface of the heart to form the visceral pericardium also termed the epicardium.

49
Q

What is the epicardium?

A

Fatty connective tissue
Sometimes used interchangeably with pericardium
Strictly it is the underlying adipose connective tissue, vessels and nerves
Contains mixture of vessels and nerves
Between pericardium and myocardium

50
Q

What is the myocardium?

A

Thickest layer of the heart
Specialised cardiac muscle
Striated
Central nuclei
Branching
Intercalated discs( can be seen as pale areas between adjacent myocytes on H&E stains, specialised connections between myocytes that join them together into long and branched chains. Not seen in any other form of muscle)
Loose fibrous connective tissue between the muscle fibres which may contain very small number of lymphocytes (endomysium)
Largest myocytes in wall of left ventricle
Atrial myocytes are smaller than those in the ventricle
Contain perinuclear neuroendocrine granules (atrial natriuretic peptide)
The heart is an endocrine organ secreting atrial natriuretic peptide
The myocytes of ventricles do not secrete this

51
Q

What are cardiac intercalated discs?

A

Connect adjacent cardiac myocytes

Contain gap junctions, adhering junctions, and desmosomes

52
Q

What is the SAN?

A

The SA node is located where the main vein from the upper part of the body (the superior vena cava) enters the right atrium.
composed of an irregular meshwork of muscle fibres three to four microns in diameter
considerably smaller than normal atrial cardiac muscle fibres
do not have intercalated discs but connect with each other by desmosomes. they contain few myofibrils and lack an organised striation pattern
cells of node are embedded in a bulky fibro collagenous support tissue containing numerous blood vessels, including a prominent central artery, the nodal artery
Numerous nerve fibres can be seen peripherally

53
Q

What is the AVN?

A

Located beneath endocardium of medial wall of right atrium, just in front of the opening of the coronary sinus and immediately above the tricuspid valve ring. It is thus situated at the base of the interatrial septum, at the junction between atria and ventricles, and between the central fibrous body and endocardium
Histologically composed of a network of small muscle fibres identical to those of the SA node, but less haphazardly arranged. As in the SA node, the fibers of the AV node are embedded in a fibrocollagenous stroma and have rich blood and nerve supplies

54
Q

What is the bundle of His?

A

The small fibers at the anterior end of the AV node are more regularly arranged and eventually become a distinct bundle of parallel fibers that forms the main bundle conducting the impulse from the AV node to the ventricles. This conducting bundle, the bundle of His, penetrates the collagen of the central fibrous body and then runs anteriorly for a short distance along the upper border of the muscle of the interventricular septum before dividing into right and left bundle branches
The left bundle arises fan-like over a broad area as individual fibres, which leave the bundle of His; the remaining fibers form a distinct right bundle branch
The left bundle branch fascicles run down beneath the endocardium of the left side of the interventricular septum in two mai group, a posterior group and a smaller anterior group
The right bundle branch runs down beneath the endocardium of the right side of the interventricular septum as a single bundle

55
Q

What are the purkinje fibres?

A

The right and left bundle branches connect with a complex network of specialised conduction fibres, the Purkinje fibres, which are large muscle fibres with a vacuolated cytoplasm owing to a high glycogen content, and scanty myofibrils. They lie in clusters of up to about six fibres
Subendocardial
Large vacuolated muscle cells
Found immediately below the endocardium, difficult to find on H&E slides
Pale on H&E
PAS highlights the glycogen risk cytoplasm of purkinje fibres magenta

56
Q

What is the endocardium?

A

Innermost layer of heart
Thin layer of fibrous connective tissue
Endothelial cells(SIMPLE SQUAMOUS)
Composed of three layers:
delay in direct contact with the myocardium
the middle layer
the innermost layer
The outermost layer is composed of irregularly arranged collagen fibres that merge with collagen surrounding adjacent cardiac muscle fibres. this layer may contain some Purkinje fibres, which are part of the impulse conducting system
The middle layer is the thickest endocardial layer and is composed of more regularly arranged collagen fibres containing variable numbers of elastic fibres, which are compact and arranged in parallel and deepest part of the layer. Occasional myofibroblasts are present
The inner layer is composed of flat endothelial cells, which are continuous with the endothelial cells lining the vessels entering and emerging from the heart

57
Q

What are Weibel-Palade bodies?

A

the storage granules of endothelialcells, thecellsthat form the inner lining of the blood vessels andheart. They store and release two principal molecules, von Willebrand factor and P-selectin, and thus play a dual role in hemostasis and inflammation.

58
Q

What is the histological structure of heart valves?

A

Regulate direction of blood flow
Covered by endothelium
Attach to central fibrous body
3 separate layers:
Fibrosa(dense fibrous CT)
Spongiosa (loose fibrous CT)
Ventricularis (collagen and elastin)
Both sides of cardiac valves are covered by vascular endothelial cells
During contraction of the ventricles (systole), blood is prevented from flowing back into the atria by two valves:
The right atrioventricular (tricuspid) valve between the right atrium and right ventricle
The left atrioventricular (bicuspid or mitral) valve between the left atrium and left ventricle
Similarly to prevent blood flowing back into the two ventricles at the end of their contraction, there are valves between the ventricles and the large vessels into which they empty:
The pulmonary valve between the right ventricle and its outflow vessel, the pulmonary artery:
The aortic valve between the left ventricle and its outflow vessel, the aorta
The heart has a fibrocollagenous skeleton, the main component being the central fibrous body, located at the level of the cardiac valves
Extensions of the central fibrous body surround the heart valves to form the valve rings, which support the base of each valve. The valve rings on the left side of the heart surround the mitral and aortic valves and are thicker than those on the right side, which surround the tricuspid and pulmonary valves
A short downward extension of the fibrocollagenous tissue of the aortic valve ring forms a fibrous septum between the right and left ventricles called the membranous interventricular septum. This is a minor component of the septum between the right and left ventricles, most of which is composed of cardiac muscle covered on both sides by endocardium. The membranous part is located high in the septal wall beneath the aortic valve
The outflow valves of the right and left ventricles, the pulmonary and aortic valves, are composed of three cup-like cusps that fit closely together when closed. Because of their shape they are sometimes called semilunar valves
The base of each valve is attached to a fibrocollagenous valve ring. The junctions between the cusps and are called commissures
The atrioventricular valves are thin flaps attached to their respective valve ring at the base, and tethered on their undersurface by the chordae tendinae. This prevents eversion of the valve leaflets into the atrium during ventricular contraction
The heart valves all have the same general structure with a dense fibrocollagenous central plate (the fibrosa), which is an extension of the fibrocollagenous tissue of the central fibrous body and the fibrocollageous valve ring. The fibrosa is covered on both surfaces by a layer of fibroeleastic tissue, and is covered by outer layers of flat endothelial cells. The thickness of the layers varies between valves, and between sites within the same valve, and with age

59
Q

Where in the heart will you find the nodules of Arantius?

A

Aortic Valve Cusps

60
Q

Describe cardiac muscle?

A
  • form of striated muscle but differs significantly from skeletal muscle
  • Like skeletal muscle, cardiac muscle is a type of striated muscle and is characterised by a similar arrangement of actin and myosin filament to mediate contraction. important differences between cardiac muscle and skeletal muscle are as follows:
    • cardiac muscle cells are mononuclear and much shorter than those of skeletal muscle;
    • long cardiac muscle fibres are produced by linking numerous cardiac muscle cells end to end via anchoring type cell junctions;
    • population of stem cells, analogous to satellite cells of skeletal muscle is not present in cardiac muscle and so regeneration following damage cannot occur.
  • individual cardiac muscle cells are linked into long chains by specialised cell junctional systems:
  • in the adult, a cardiac muscle cell is about 15 micrometres in diameter and about 100 micro metres long , with essentially position nucleus. Intercellular junctions, which can be seen in light microscopic preparations as faint lines running transversely across fibers, are termed intercalated disks. These contain three types of cell junction:
    • Desmosomal junctions tightly link adjacent cells via anchors involving the intermediate filament
    • adherence type junction’s anchor the acting fibres of sarcomeres to each end of the cell
    • communicating gap junctions facilitate the passage of membrane excitation and thereby synchronisation and muscle contraction
  • contraction of cardiac muscle cells is regulated by cytosolic CA2+ ion concentration in a manner virtually identical to that for skeletal muscle but:
    • the cardiac muscle transversed tubular system consists of much wider invaginations of the cell surface
    • sarcoplasmic reticulum associated with the T tubules is neither as regular nor as well organised as in skeletal muscle
    • Hey chill myocardial fibres are smaller than those of the ventricles and contain small neuroendocrine granules, which are usually sparse and located close to the nucleus; they are most numerous in the right atrium. these granules secrete atrial natriuretic hormone when the atrial fibers are stretched excessively.
    • Atrial natriuretic hormone increases the excretion of water and sodium and potassium ions by the distal convoluted tubule of the kidney. It also decreases blood pressure by inhibiting renin secretion by the kidneys and aldosterone secretion by the adrenals
61
Q

What is respiratory epithelium?

A

Lines the tubular portions of the respiratory tract
• Pseudostratified ciliated columnar epithelial cells (all cells are in contact with the basement membrane)
• interspersed with goblet cells

62
Q

What are the features of the histology of the nose?

A

• Function of filtration, humidification, warming & olfaction
• Keratinising & non-keratinising squamous epithelium
• Respiratory epithelium
• Richly vascular lamina (so it can rapidly warm and humidify
air - rapid heat exchange) containing seromucinous glands
- The nose - olfaction:
• Roof of the nasal cavity, extending down septum and lateral wall
• Pseudostratified columnar epithelium of olfactory cels
• Serous glands of bowman
• Richly innervated lamina propria
(picture)
• Olfactory receptor cells (picture) - bipolar neurones - dendrite extends to surface to become club-shaped ciliated olfactory vesicle

63
Q

What are the features of the histology of the nasopharynx?

A
function of Gas transport, humidification, warming & olfaction
• Lined by respiratory epithelium
64
Q

What are the features of the histology of the nasal sinuses?

A

Lower the weight of the skull
• Add resonance to voice
• Humidify & warm inspired air
• Lined by respiratory epithelium

65
Q

What are the features of the histology of the larynx?

A

Cartilaginous box
• Voice production
• Lined by respiratory epithelium
• Loos fibrocollagenous stroma with seromucinous glands

66
Q

What are the features of the histology of the vocal cords?

A

• Voice production
• Stratified squamous epithelium overlying loose irregular
fibrous tissue (Reinke’s space)
• Almost no lymphatics

67
Q

What are the features of the histology of the trachea?

A
  • Conducts air to and from the lungs
  • Lined by respiratory epithelium
  • Seromucinous glands in submucosa
  • Tracheal muscle posteriorly
  • C-shaped cartilaginous rings
68
Q

What are the features of the histology of the bronchi and bronchioles?

A
  • Clara cells - many large ribosome, ER & granules
    • Most numerous in terminal bronchioles
    • Contain; mitochondria, smooth ER, secretory
    granules, no cilia, vesicular cytoplasm
    • Secretory function
69
Q

What are the features of the histology of the respiratory bronchioles?

A
• First part of distal respiratory tract
• Gas exchange as well as transport
• Link terminal bronchioles and the
alveolar ducts
• Cuboidal ciliated epithelium
• Spirally-arranged smooth muscle
• No cartilage
70
Q

What are the features of the histology of the alveoli?

A
• 150-400 million/lung
• GAS EXCHANGE
- Alveoli Type 1 pneumocyte:
• 40 % of cell population
• 90% of surface area
• Flattened cells, flattened nucleus, few
organelles - main gas exchangers
71
Q

What are the features of the histology of the alveoli type 2 pneumocytes?

A
• 60 % of cell population
• 5-10% of surface area
• Rounded cells, round nucleus, rich in
mitochondria, smooth and rough ER
• PRODUCES SURFACTANT
72
Q

What are the features of the histology of the alveolar macrophages?

A
  • Luminal cells, also present in the interstitium
  • Phagocytose particulates including dust and bacteria
  • Enter lymphatics or leave via mucociliary escalator
73
Q

What are the features of the histology of the alveoli blood-air barrier?

A
  • 1 pneumocyte thick
  • Fused basement membrane of pneumocyte and capillary
  • Vascular endothelial cell
  • 200-800nm thick
74
Q

What are the features of the histology of the visceral pleura?

A
  • Flat mesothelial cells
  • Loose fibrocollagenous tissue
  • Irregular external elastic layer
  • Interstitial fibrocollagenous layer
  • Irregular internal elastic layer
75
Q

Describe the histology of the mouth (what is present and what kind of epithelium)?

A

The lip displays a mucosal covering typical of the mouth (stratified squamous non-keratizing epithelium) and its abrupt transformation into skin (stratified squamous keratized epithelium) at its margin.

The epithelial lining sits on a connective tissue layer (submucosa) containing collagen and elastic fibres. The deeper layers often contain glands and skeletal muscle fibres that help to change the shape of the oral cavity.

Many small blood vessels lie in the submucosa and fluid from these helps to keep the epithelium moist.
There is an abrupt transition to a stratified squamous keratinising epithelium at the margin of the lips

76
Q

Describe the histology of the tongue (What is present and what kind of epithelium)?

A

The tongue is covered by a stratified squamous epithelium that remains non-keratinized on its ventral surface but is often heavily keratinized on its dorsal surface due to constant abrasion of this surface.

Inside, it contains coarse bundles of skeletal muscle that run in different directions. Some of these insert onto the lower jaw (extrinsic fibres) while others attach only to the fibrous connective tissue underlying the mucosa (intrinsic fibres).

Many mixed sero-mucous salivary glands are embedded within the tongue. So too are lymph nodules, particularly in the posterior thirdof the tongue (e.g. lingual tonsils).

77
Q

Describe the histology of the papillae and taste buds (What is present)?

A

The dorsum of the tongue is thrown into complex folds known as papillae. Tall, pointed filiform papillae are the most common and cover the whole of the anterior two thirdsof the tongue, producing a rasp-like surface.

Less numerous mushroom shaped fungiform papillae are found at the tip and sides of the tongue.

Pale-staining taste buds are embedded in the epithelium on the lateral sides of these papillae.

A V-shaped row of dome-shaped circumvallate papillae separate the anterior two thirdsand the posterior thirdon the tongue’s surface. These too bear taste buds.

78
Q

Describe the histology of the oesophagus (Function, what is present, and what kind of epithelium)?

A

Swallows food

The oesophagus is mostly lined by a stratified squamous non-keratinized epithelium. Underneath this is a thin lamina propria and a narrow muscularis mucosa of smooth muscle.

This muscle layer becomes thicker and more prominent at the distal (gastric) end of the tube. Below the thoracic diaphragm the epithelium is often transformed into a simple columnar type similar to that which lines the cardiac region of the stomach. This region of the oesophagus can become the site of pathological change.

The submucosa contains many sero-mucous glands whose secretions help to lubricate the oesophagus. At the distal end of the oesophagus the submucosal layer contains many large, thin-walled veins. These may become the site of oesophageal varicosities.

At the proximal end of the oesophagus the outermost layer of muscle (muscularis externa) is composed mainly of skeletal muscle but at the distal end it is composed mostly of smooth muscle.

79
Q

Describe the histology of the stomach (what is present, what is the function, what kind of epithelium)?

A

Digests food

The stomach can be divided into 4 regions:

  1. the cardia
  2. the fundus
  3. the body
  4. the pyloric

The fundus and body show very similar histological structure particularly with respects to their gastric glands. The cardia and pylorus have a different histological appearance.

Throughout the stomach the mucosa is thrown into visible longitudinal folds known as rugae.
The stomach is lined by a simple columnar epithelium punctuated by gastric pits into which the gastric glands drain.

The muscular coat (muscularis propria) is threelayers thick. Compared with the rest of the gut tube it has an additional oblique layer of fibres closest to the mucosa that helps to churn up the food within the stomach.

The mucosa of the stomach contains many tubular glands within its mucosa. These fill the lamina propria and discharge their secretions into gastric pits that communicate with the lumen of the stomach.

There are threemain types of cell within the glands of the fundus and body of the stomach, (i) mucous neck cells that provide a lubricatory, acid-resistant mucus, (ii) parietal cells that secrete HCl and intrinsic factor and (iii) chief cells that produce digestive enzymes, notably pepsin (which is secreted in an inactive form - pepsinogen).

Full gastric glands are present in the wall of the body and fundus of the stomach. Glands of the cardia and pylorus also have gastric glands but they are devoid of parietal and chief cells. The remaining mucous neck cells provide protective and lubricatory secretions.

The stomach is lined by a simple columnar epithelium. These tall cells produce a special acid-resistant mucin that protects the lining of the stomach.

The surface epithelium also has deep invaginations called gastric pits, (openings shown by green arrows) at the bottoms of which are the gastric glands. Several tall straight or branched glands open into each gastric pit. The glands contain different types of secretory cell. These glands fill the lamina propria.

The submucosa consists of loose connective tissue often with prominent blood vessels.

The muscularis propria consists of thick bands of smooth muscle often subdivided into threelayers.

The gastric glands of the cardiac and pyloric regions of the stomach are shorter than those of the body or fundus and are coiled rather than straight. They are composed mainly of mucous neck cells. These are similar to those seen in the glands of the body and fundus where they are confined to a narrow band at the entrance to each gland.

Scattered among the neck cells of the pyloric region are isolated cells that produce gastrin and a bombesin-like peptide. Furthermore, throughout the whole of the gastric mucosa there are scattered pale-staining endocrine cells that produce serotonin, somatostatin and vasoactive intestinal peptide (VIP). Together these cells play an important role in regulating the breakdown and delivery of foodstuffs to the duodenum which occurs during the digestion process.

80
Q

Describe the histology of the intestine in general?

A

Digest food
Absorb food
Absorb water
Resist bugs

Contain endocrine cells

Made up of lumen, mucosa, submucosa, muscularis propria, and serosal surface

All smooth muscle

Ganglion cells are visible
Hirschsprung’s disease-where ganglion cells aren’t present so no movement in section of the bowel

Interstitial cells of Cajal- in muscular wall of the bowel, they are the pacemaker cells in the bowel,Can stain them,Can form tumours. Called gastrointestinal stromal tumour (GIST)

The lining of the intestine is thrown into circular folds that are visible with the naked eye. These are known as plicae circulares. They are most numerous in the jejunum and least numerous in the distal part of the colon. They increase the surface area of the gut available for absorption.

The surface area is the small intestine is further augmented by microscopic leaf-like or finger-like projections of the mucosa known as intestinal villi.
The villi are covered by a simple columnar epithelium with twomain cell types, enterocytes (absorptive cells) and goblet cells (mucus secreting cells). These cells are short lived but are replaced by cells that originate in the crypts.

Each villus contains in its core a small arteriole, a thin walled venule and a blind-ended lymphatic (lacteal). They also contain smooth muscle cells that rhythmically shorten the villus thereby “milking” the blood and lymph from the villus. The venules and lacteals carry absorbed nutrients to the liver.

Between the villi are straight tubular glands known as crypts of Lieberkuhn. These contain a stem cell population. Newly formed cells migrate from the crypts on to the surface of the villi and are eventually sloughed off from the tips, the whole process taking about fivedays.

Enterocytes are the major absorptive cell of the small (and large) bowel.

Each cell possesses about 300 short, closely packed processes known as microvilli on its apical surface.
These processes can not be seen individually with a light microscope buten massegive rise to a brush border.

Arising from the outside surface of these microvilli is a well-developed glycocalyx that acts as a filter and as an anchorage for exo-enzymes.

Most nutrients are aborbed across this epithelium although water and some glucose is able to be taken up via pathways between the cells.

The presence of high concentrations of hexose sugars within the glycocalyx means that the brush border (like the goblet cell) stains intensely by the Periodic Acid Schiff (PAS) procedure.

81
Q

Describe the histology of the duodenum (what is the function, what is present)?

A

Digests food
Absorbs food
Resists bugs

Key is to maximise surface area
Villi, Microvilli, length of the small intestine etc

The duodenum is the first of the three segments that make up the small intestine. As the name suggests it is 12 inches (30 cm long). It has a relatively smooth lining with few plicae circulares.

The villi are broad leaf-like structures and the epithelium has relatively few goblet cells. (However, it may be worth noting that the shape of the villi is not sufficient information by itself to determine whether the tissue is from the duodenum or jejunum. Histopathologists look for the presence of Brunner’s glands to determine whether this is duodenum or jejunum.)

The submucosa of the duodenum is filled by a mucous secreting Brunner’s gland. Its alkaline secretion helps to neutralise the chyme emerging from the stomach.

Duodenal crypts, like those of the rest of the intestine contain newly formed enterocytes and goblet cells. In the small intestine these cells migrate on to the villi. In the large intestine where there are no villi, the cells simply spread out over the flattened surface of the gut.
The stem cells in the crypts give rise to each of the differentiated cell types that populate the crypts and villi. Dividing cells can be recognised by their compact very dark staining nuclei or by sets of chromosomes if the nuclear membrane has broken down.

At the bottom of the crypts are a population of differentiated Paneth cells. These secrete lysozyme, an enzyme important for the breakdown of bacterial cell walls. They play an important part in regulatiing the bacterial flora of the gut. The cells can be recognised by their bright pink-staining cytoplasmic granules.

Note the bright pink staining granules in the Paneth cells.

82
Q

What is the histology of coeliac disease?

A

Villi get lost in the duodenum and therefore are unable to absorb
Villous atrophy
Crypt hyperplasia
Mass of extra lymphocytes reacting to glyodine

83
Q

Describe the histology of the jejunum (function, what is present)?

A

Also set up for maximising absorption

The jejunum is the second (middle) section of the small intestine. It has close-packed plicae circulares, the villi are long and narrow and the crypts are relatively short. Many goblet cells are present within the epithelium.

The submucosa is variable in thickness but is generally very loose so that the mucosa is almost detached from the muscularis externa outside it. Unlike the duodenum, the jejunum does not have Brunner’s gland in its submucosa nor does it have the large lymph nodules (Peyer’s patches) characteristic of the ileum. The absence of these 2 features helps to distinguish this part of the small intestine from the other two sections.

Lymph nodules are present in the lamina propria but they do not normally penetrate into the submucosa.

84
Q

Describe the histology of the ileum (function, what is present)?

A

Also set up for maximising absorption

The ileum is the third and last segment of the small intestine. Here the plicae circulares are not as closely packed as in the jejunum and the villi are not as tall. Goblet cells increase in number towards its distal end.

Large patches of lymphoid tissue (Peyer’s patches) are present in the submucosa and in places these can be seen to erupt through the muscularis mucosa into the lamina propria.

Note too that the villi are generally not as tall as those of the jejunum

85
Q

Describe the histology of the appendix (function, what is present)?

A

No one knows what it does
May possibly replace the good flora after a colonic infection

The vermiform appendix arises from the caecum, the first part of the large intestine. It is lined by a simple columnar epithelium with goblet cells but with no villi and only a few rudimentary crypts.

The lamina propria and submucosa are filled with lymphoid tissue. The amount of lymphoid tissue present is large in children but declines with age.
There is no muscularis mucosa but the muscularis externa shows twolayers of smooth muscle similar to the rest of the intestine. The taenea coli originate at the base of the appendix and run the whole length of the large intestine

86
Q

Describe the histology of the colon (function, what is present)?

A

Absorbs food
Absorbs water
Resists bugs

No villi
Flat mucosal surface

The colon has foursegments: ascending, transverse, descending and sigmoid colon. These segments together with the caecum at its proximal end and the rectum that follows it all have a similar histological appearance.

There is very little macroscopic folding of the lining of the large bowl.

There are no intestinal villi in the large intestine. Instead, the mucosa consists of close packed intestinal crypts that mainly contain enterocytes and abundant goblet cells. The lamina propria is restricted in volume due to the packed nature of the crypts but a prominent muscularis mucosa separates the mucosa from underlying tissues.

The mucosa and submucosa frequently have lymph nodules embedded within them, part of the GALT system of immunologic defense.

The muscularis externa consists of a thickened inner circular layer of smooth muscle and an outer layer that is drawn up into

threelongitudinal bands (ribbons) known as taeniae coli. These brands are clearly visible in a fresh gross specimen.

87
Q

Describe the histology of the anus/rectum(function, what is present)?

A

The rectum has a similar histological appearance to the colon, being lined by a simple columnar epithelium. The anal canal, on the other hand, is lined mainly by a stratified squamous epithelium that becomes keratinized at its distal end.

The submucosa contains fat and a prominent (internal) plexus of veins that may give rise to anal varicosities.

The smooth muscle of the mucularis externa is thickened to form the internal anal sphincter and is surrounded by striated muscle of the external anal sphincter (derived from the pelvic bowl).

The peri-anal skin contains hair follicles and modified sebaceous glands.

88
Q

Describe the blood supply of the liver?

A

Hepatic Artery
Oxygenated
25%
The hepatic artery perfuses the liver with oxygenated blood from the coeliac axis branches of the aorta

Hepatic Portal Vein
Deoxygenated
75%
The hepatic portal vein carries blood from the digestive tract and spleen to the liver; the blood from the digestive tract being rich in amino acids, lipids and carbohydrates absorbed from the bowel, and that from the spleen being rich in haemoglobin breakdown products.

89
Q

Describe liver vasculature?

A

In the liver, the two input circulations(terminal branches of the portal vein and hepatic artery) discharge their blood into a common network of anastomosing small vascular channels, the sinusoids surrounding hepatic cells

Blood leaves the liver via the hepatic vein which eventually drains into the inferior
vena cava - this blood is deoxygenated, detoxified & contains the normal homeostatic nutrient levels

The terminal parts of the hepatic portal and arterial systems run together in a connective tissue framework called portal tracts, which also contain bile ductules
After entering the liver at the porta hepatis, the portal vein divides within the liver into progressively smaller branches (interlobar, segmental, and interlobular branches) which then branch further, eventually forming an extensive anastomosing network of terminal portal venules. Lateral side branches (inlet venules) of the terminal portal venules empty blood into the sinusoids, where it blends with blood from the terminal hepatic artery branches

The hepatic artery divides into successively smaller branches, the terminal elements running with the terminal branches of the hepatic portal vein before emptying into the hepatic sinusoids by short side branches (the arteriosinusoidal branches)

A peribilliary plexus of small arterial branches supplies oxygenated blood into the larger intrahepatic bile ducts before draining into the sinusoids, where it blends with blood from the portal venous system

The sinusoids are surrounded on all sides by hepatocytes. In this way, blood following through the liver is exposed to a massive surface area of liver cells
Perisinusoidal space of Disse is the main site where material is transferred between the blood-filled sinusoids and hepatocytes. This transfer is in both directions, with some material being taken up by hepatocytes as well as being secreted

The hepatic sinusoids are partly lined by phagocytic cells (Kupffer cells), which are a form of macrophage and are derived from circulating blood monocytes
Blood which has passed through the functioning liver parenchyma enters terminal hepatic venules (central veins of the lobules), which in turn unite to form intercalated veins; these then fuse to form larger hepatic vein branches. Hepatic veins are devoid of valves and open separately into the inferior vena cava as it passes through the liver on its way to the right atrium

Lymphatic fluid drains from the liver to the thoracic duct
Fluid drains from the space of Disse into the portal tracts, in which it travels in fine channels. These lymphatic channels increase in size as the branches of the portal tracts merger towards the hepatic hilum. Finally, lymph drains into the thoracic duct. Such is the extent of the lymph production by the liver that it comprises about half of the total lymph flow in the body under resting conditions

90
Q

Describe Sinusoids?

A

Highly specialised blood vessels

Thin discontinuous fenestrated endothelium

No basement membrane

Endothelial cells interspersed with fixed macrophages and Ito cells.

The capillary wall is often too thin and/or collapsed against the adjoining hepaocytes to be resolved. These vessels sit on a delicate meshwork of reticulin (collagen type III fibres) and are separated from the cords of hepatocytes by the space of Disse, from which blood cells, but not plasma are normally excluded
Included within the lining endothelium of the sinusoids are specialised macrophages known as Kupffer cells

They phagocytose and destroy many blood borne pathogens that pass through the liver. They are also responsible (in part) for the production of bilirubin that is subsequently taken up and excreted by the hepatocytes.

Their presence in the liver can be demonstrated by the uptake of coloured products or dyes.

This has been stained against macrophages

91
Q

What are the functions of hepatocytes?

A

Bile synthesis and secretion

Excretion of bilirubin

Protein metabolism

Carbohydrate metabolism

Storage

Conjuction and elimination

92
Q

Describe Bile Synthesis and secretion in the hepatocytes?

A

liver produces bile, which is an alkaline secretion containing water, ions, phospholipids, bile pigments (mainly bilirubin glucuronide) and bile acids (glycocholic and taurocholic)

93
Q

Describe excretion of bilirubin in the hepatocytes?

A

Bilirubin is produced in the spleen from the breakdown of the haem component of haemoglobin. In the liver the bilirubin is conjugated with glucuronic acid, and the conjugate (bilirubin glucorinide) is excreted in the bile and thence the faeces

94
Q

Describe protein metabolism in the hepatocytes?

A

The liver is centrally involved in protein metabolism. It brings about deamination of amino acid; it produces urea from circulating ammonia; it also interconverts amino acids and produces the so-called non-essential amino acids. The liver synthesises many proteins including most of the plasma proteins such as albumin, blood clotting factors such as fibrinogen, and prothrombin
(the profile of proteins secreted by the liver can be influenced by cytokines circulating in the blood. In patients with inflammatory disorders, circulating cytokines can increase the concentration of several liver-produced proteins in the blood, such as fibrinogen, transferrin, and serum amyloid A protein. The production of some other proteins is downregulate, for example albumin. This is called an acute-phase response)
the deamination of amino acids and the production of urea

95
Q

Describe carbohydrate metabolism in the hepatocytes?

A

Lipids and amino acids are converted into glucose in liver by gluconeogenesis. The liver makes and stores glycogen as well as forming intermediary compounds in carbohydrate metabolism

96
Q

Describe storage in the hepatocytes?

A

The liver acts a store for vitamins A, D, and B12. It stores iron as ferritin. the creation and storage of energy in the form of glycogen and fats

97
Q

Describe conjugation and elimination in the hepatocytes?

A

The SER of the liver possesses large numbers of enzymes that break down or conjugate metabolites or toxic substances. Certain hormones are eliminated by the liver

98
Q

What is the portal triad?

A

At the outer corners of the lobule are portal triads, a collection of vessels that includes (a) a small muscular arteriole carrying oxygenated blood from the hepatic artery, (b) a thin walled vein carring deoygenated but nutrient rich blood from the intestine and a bile ductule that carries bile away from the hepatocytes to the gallbladder and bile duct.

99
Q

What are the features of hepatocytes?

A

Intimately associated with sinusoids

Are polyhedral cells with Three important surfaces:
Sinusoidal (70%) (permits exchange of material with blood, Space of Disse)
Canalicular (15%) (permits excretion of bile)
Intercellular (15%)

Space of Disse is important as it contains reticulin and Ito cells (hepatic stellate cells)

Nuclei are large, spherical and central, and contain scattered clumps of chromatin and prominent nucleoli. Many cells are binucleate, and nuclei are frequently polyploid; progressively more tetraploid nuclei develop with age

The hepatocytes usually store large quantities of glycogen (starch) and triglycerides (lipid) within their cytoplasm, both of which can be easily demonstrated histochemically but which are not easy to see using routine H&E staining.

Golgi is large and active, or small and multiple, and is mainly seen near the nucleus, with an extension lying close to the canalicular surface

Vesicles and tubules of the abundant SER and RER are continuous with the Golgi. There are numerous free ribosomes in the cytosol, as well as large glycogen deposits and some lipid droplets, the glycogen often being closely related to the smooth endoplasmic reticulum.

Lysosomes of various sizes are numerous, some containing lipofuscin and lamellated lipoprotein. They are particularly large and numerous near the canalicular surface

Peroxisomes usually number 200-300 per cell
Mitochondria are also abundant, numbering more than 1000 per cell, and are randomly scattered. This vast mitochondrial component gives the hepatocyte cytoplasm its eosinophilic granular appearance in H&E-stained paraffin sections

Sinusoidal surfaces account for 70% of total hepatocyte surface(site where material is transferred between the sinusoids and hepatocyte)

Canalicular surfaces are the surfaces across which bile drains from the hepatocytes into the canaliculi. Canalicular surfaces are 15% of hepatocyte surface and are closely apposed except at the site of a canaliculus, which is a tube formed by the exact opposition of two shallow gutters on the surface of adjacent hepatocytes.

Canaliculi are about 0.5-2.5 microns in diameter, being smaller close to the terminal hepatic venule, and are lined by irregular microvilli arising from the canalicular surfaces of the hepatocytes

Cell membrane around canalicular lumen is rich in alkaline phosphatase and adenosine triphosphate, and the canalicular lumen is isolated from the rest of the canalicular surface by junctional complexes
The intercellular surfaces are the surfaces between adjacent hepatocytes that are not in contact with sinusoids or canaliculi.

Intercellular surfaces account for about 15% of the hepatocyte surface. They are comparatively simple, but specialised for cell attachment and cell-to-cell communication via communicating junctions

Glycogen particles (rosettes) and lipid droplets are almost always evident within the cytoplasm of these cells.

100
Q

Is there spatial variation hepatocyte metabolic profiles?

A

Hepatocytes have different metabolic profiles depending on how close they are to portal tracts

101
Q

What are the two functional organisations of hepatocytes?

A

Lobular concept (Most nomenclature in disease uses the lobular concept)

The liver can be functionally divided into structures called acini

102
Q

Describe the lobular concept?

A

In the lobule, three main zones of hepatocytes are identified, termed centrilobular, periportal, and mid zones.
Hepatocytes close to the portal tracts are exposed to blood that contains the highest oxygen concentration and contain enzymes involved in oxidative reactions. These cells make and store glycogen and produce and secrete proteins.
Hepatocytes furthest away from the portal tracts- those adjacent to the central venules- are most distant from the oxygenated arterial blood supply. These hepatocytes have little capacity for oxidative activities and contain many esterases, being involved in conjugating and detoxifying reactions
Hepatocytes in between these extremes have intermediate metabolic properties
The outer layer of periportal hepatocytes adjacent to the portal tract is called the limiting plate; it is the first group of hepatocytes to be damaged in inflammatory liver disorders that primarily involve the portal tracts
By convention, liver divided into classic lobules

Classic lobule:
Area drained by one central hepatic venule
An artificial construct for understanding hepatic architecture
Roughly hexagonal
Some hepatocytes will be more richly oxygenated than others (not all hepatocytes are equal)
Those nearer to the portal vein and hepatic artery will be better supplied
Those near centre of lobule are most deprived

103
Q

Describe the acinar concept?

A

3 zones
Zone I: those hepatocytes closest to the portal tract which synthesise proteins and glycogen
Zone II: hepatocytes between zones I and III
Zone III: Those hepatocytes adjacent the central venule which contain esterases and conjugating enzymes

The acinus:
Architectural concept based around the blood supply rather than drainage
An artificial construct for understanding hepatic architecture

104
Q

Describe the intrahepatic biliary tree?

A

The bile canaliculi carry the bole back to the portal tracts

As the canaliculi approach the bile ductules in the portal tracts, they open into the short passages lined by small cuboidal cells (the canals of Hering). From here, bile flows into the bile ductules in the portal tract

Bile ductules anastomose freely, fuse, and increase in size to form larger ducts, the trabecular ducts
Many of these ducts fuse to from large intrahepatic ducts, which converge near the liver hilum into the main hepatic ducts

The small tributaries of the intrahepatic biliary tree fuse to become increasingly larger channels, eventually fusing to become two large ducts, the right and left lobar bile ducts. These join at the hilum of the liver to form the common hepatic duct, which is the first part of the extrahepatic bile duct system
About 3-4cm after leaving the liver from the common hepatic duct receives the cystic duct and becomes the common bile duct

The common bile duct is about 6-7cm long and opens into the duodenum at the ampulla of Vater, having passed through the head of the pancreas and combined with the pancreatic duct

The biliary tree is lined throughout by a cuboidal epithelium. In the smaller vessels it is a single layered (simple) epithelium but towards distal end it often becomes stratified.

105
Q

Describe the histology of the gallbladder?

A

Gallbladder is an ovoid sac with a muscular wall and is capable of moderate distension. It concentrates and stores bile, receiving dilute watery bile from the common hepatic duct and emptying thick, concentrated, variably mucoid bile into the common bile duct

Concentrates and stores bile

Expels bile via common bile duct into duodenum

Simple columnar resting on a basement membrane

Bile is transported in and out of the gallbladder through a short duct, the cystic duct. This duct contains a spirally arranged outgrowth of mucosa, which forms the spiral valve of Heister

The gallbladder wall has a mucosa which comprises an absorptive epithelium resting on a highly vascular lamina propria. There is no muscularis mucosa. The muscle layer is normally thin and apparently haphazardly arranged but with a tendency to be circumferential. There is an outer dense fibrous layer which is partly covered by peritoneal serosa, but partly loosely binds one aspect of the gallbladder to the underside of the liver.

The lining cells have numerous microvilli on their luminal surfaces and complex interdigitations of their lateral walls. These differently specialised surfaces are separated by junctional complexes

Gallbladder epithelial cells are adapted for salt and water absorption, and have abundant basal and apical mitochondria, and Na+ and K+ transport ATPases in their lateral walls

Na+ and Cl- ions are actively pumped out of the cell cytoplasm into the lateral intercellular space to produce an osmotic gradient between it and the gallbladder lumen. Water is therefore drawn into the space from the lumen and then enters the abundant capillary network in the lamina propria

Gallbladder epithelium is thrown up into folds or plicae, which flatten when the gallbladder is distended

Concentrated and compacted bile products (gallstones) may be present in the lumen of the gallbladder

106
Q

Describe exocrine pancreas features?

A

Synthesise and secrete enzymes and bicarbonate-rich fluid into the duodenum

Poorly defined fibrous capsule with septa dividing gland into lobules

Epithelial cells arranged in acini

The exocrine portion of the pancreas accounts for over 90% of the mass of the gland. It is a wholly serous gland (watery secretion, enzyme rich). It produces a range of digestive enzymes that are synthesized alongside each other in the same cells and packaged together in secretion granules in the upper part (apex) of each cell

Following stimulation from food entering the duodenum they are induced to release their stored enzymes that only become activated when they reach the alkaine environment of the duodenum.

Stimulation with secretin induces the release an alkaline fluid which is mainly produced by centro-acinar cells and small duct cells

Stimulation with CCK causes the release of the enzymes from the cells by exocytosis

107
Q

Describe pancreatic acinar cells?

A

Epithelial

Pyramidal shape

Basally- rich in RER

Apically-Zymogen granules (enzyme precursors) towards apex of the cell

108
Q

Describe the histology of the pancreatic duct system?

A

Centroacinar cells (located in the centre of the acinar)

Intercalated ducts

Interlobular ducts

Main pancreatic duct

The pancreas resembles a bunch of grapes. Each acinus (grape) has a narrow stalk-like intercalated duct that connects it to the main duct. Eventually the larger ducts form one or two main ducts that enter with the common bile duct into the secondpart of the duodenum

The ducts are lined by a simple cuboidal epithelium that may become stratified at its distal end. The duct cells produce most of the fluid component of the secretion