Introductory Pathology 5-13 Flashcards

0
Q

What is Pitting Oedema?

A

With severe diffuse subcutaneous oedema, a finger pushed into the expanded interstitium leaves an indentation.

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1
Q

Describe Dependent Oedema

A

In generalised oedema, the fluid tends to sink with gravity so that the ventral abdomen and limbs are mainly affected.

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2
Q

What is Hydrothorax/ hydropericardium?

A

Accumulation of oedema fluid in the pleural cavity/ pericardial sac

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3
Q

What is Ascites?

A

Accumulation of oedema fluid in the peritoneal cavity

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4
Q

Describe Anasarca?

A

Severe, generalised oedema involving cavities and subcutis

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5
Q

Name the four main mechanisms which underpin the development of oedema?

A

Increased blood hydrostatic pressure,, increased vascular permeability, decreased plasma colloidal-osmotic pressure, lymphatic obstruction.

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6
Q

Describe the main differences between transudate and excudate

A

Transudate: clear or pale yellow, thin and serous, 0.05-0.5% protein, no coagulation as no fibrinogen, very low cell content, mesothelial cells, some macrophages/lymphocytes
Exudate: Dark yellow, red or brown, often cloudy, viscous, usually 2-4% protein but can be higher, contains fibrinogen so will coagulate, more macrophages/lymphocytes/neutrophils, usually caused by inflammation.

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7
Q

Describe the most common cause of septic shock.

A

Mediated by vascular and inflammatory mediators released in response to bacteria or fungal elements The most common cause is endotoxin, a lipopolysaccharide (LPS) in the cell wall of gram negative bacteria. LPS is a pattern associated molecular pattern (PAMP). It binds CD14 and toll like receptor 4. TLRs are membrane molecules that allow a wide range of microbes to activate cells. Effect of LPS is to activate macrophages and release of TNF, Il-1, Il-6, IL-8, and activate factor XII.

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8
Q

Describe the Clinical and morphological Features of shock

A

Hypotension, Weak pulse and tachycardia, hyperventilation, decreased urine production, hypothermia. Lesions depend on initiating trigger, congestion and pooling of blood, oedema and haemorrhageg, thrombosis, cellular necrosis.

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9
Q

Describe the Non progressive stage of Shock.

A

The body compensates by increasing sympathetic nervous output, leading to increased cardiac output and arteriolar vasoconstriction, raising blood pressure. Blood flow maintained to critical organs, heart kidneys and brain. Renin angiotensin system stimulated.

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10
Q

Describe the progressive stage of shock.

A

Progressive Stage: prolonged or severe hypovolaemia overcomes compensatory mechanisms. There is blood pooling, tissue hypoperfusion and cellular injury. The cell shifts to anaerobic respiration leading to lactic acid production and decreased ATP production, cell membranes damaged, lysosomal enzymes released and necrois.

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11
Q

Describe Irreversible shock

A

Irreversible: mechanisms aimed at vasoconstriction are overcome, widespread vasodilation and multiorgan failure.

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12
Q

Describe a thromboembolism

A

The most common type - fragments of thrombi detach and spread throughout the circulation. Examples include in bacterial endocarditis of heart valves in large animals fragments break off the infected valvular thrombus - infective emboli in the circulation - multifocal abscesses in other organs eg kidneys.

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13
Q

Describe a Gas embolism

A

If a large enough volume of air is injected into the circulation it can accumulate in the pulmonary trunk and form a fatal airlock.

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14
Q

Describe a fat embolism.

A

Adipocytes from the bone marrow may be released into the circulation following bone fractures. Especially affects the CNS and pulmonary circulation.

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15
Q

Describe a tumour cell embolism.

A

Malignant neoplasms may erode into the veins and lymphatics forming friable thrombi and embolic fragments breakoff and circulate to other sites (metastasis) tumour emboli lodge in capillary beds such as lung, spleen, liver and kidney where they grow to produce secondary tumours.

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16
Q

Describe how parasites can be a type of emboli.

A

Heartworms in dogs may embolize into the pulmonary trunk when they die following anthelmintic treatment. Strongyle larvae in horses, filarial worms in cattle and cats and aberrant fluke larvae in cattle and sheep may all embolise and the significance depends on their final location.

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17
Q

How may a foreign body act as an emboli?

A

Fragments of skin/hair; fibrocartilagenous emboli of degenerate disc material etc.

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18
Q

What is ischaemia?

A

Ischaemia is reduced blood flow to a tissue/organ and results in tissue hypoxia. Usually arteries or arterioles are involved. Venous thrombosis may cause infarction but typically causes congestion. Arteriospasm - arterial trauma, ergotism. Compression of vessels - ligatures, tumours, torsion. Thromboembolism - obstruction by embolic fragments.

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19
Q

The extent and consequences of Ischaemia depend on several factors such as;

A

Degree of occlusion (partial or complete), speed of occlusion (sudden onset or gradual), presence of collateral circulation and vulnerability of tissues to ischaemia (eg neurones and cardiac mycocytes more susceptible than fibrous tissue).

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20
Q

What is Infarction?

A

A segmental or localised area of ischaemic necrosis due to occlusion of the blood supply. The embolus may be bland, infective or neoplastic. The affected area typically has a wedge shape. The colour depends on the degree of vascular engorgement and co-existing inflammation or infection.

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21
Q

Describe the microscopical process of Infarction.

A

Coagulative necrosis occurs so the outline of the coagulated cells is preserved, there is increased eosinphilia of affected area and loss of cellular detail. Denaturation of the structural proteins and enzymes is the primary cause of necrosis and there is no proteolysis of the cell. Necrotic tissue is removed and replaced by either regeneration or fibrosis which forms a scar. In the brain infarcts cause liquefactive necrosis and necrotic tissue is digested.

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22
Q

What is Disseminated intravascular Coagulation?

A

DIC is characterised by the activation of coagulation within the vascular system resulting in deposition of fibrin in the small blood vessels and consumption of coagulation factors and platelets. The fibrin deposition within blood vessels lads to vascular obstruction and microinfarction. The fibrinolytic system is activated which removes some fibrin but also uses up clotting factors and forms fibrin degradation products. The process begins as hypercoagulability with a tendency to infarction which progresses to a severe, bleeding tendency. (haemorrhagic diathesis).

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23
Q

What is Dysplasia?

A

An abnormal pattern of tissue growth

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24
Q

Describe Benign neoplasia vs malignant neoplasia.

A

Benign is well differentiated, uniform cell size and shape, normal nuclear morphology, few mitosis, encapsulated, no metastases. Malignant are poorly differentiated, variable cell size and shape (pleomorphic), abnormal nuclear morphology, increased mitoses, some bizzarre, non-encapsulated and infiltrative, metastasises.

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25
Q

Describe Ovine pulmonary Adenocarcinoma

A

This is a lung neoplasm in sheep which is caused by infection with a virus known as Jaagsiekte sheep retrovirus. The neoplastic cell is either the clara cell found in the terminal bronchioles of the lung or the type II pneuomocyte which lines the alveoli of the lung. Both of these are surfactant producing cells - overproductino of surfactant is one of the obvious clinical signs of the disease. Grossly the tumour forms firm grey nodules in the lungs. Histologically the neoplastic epithelial cells form clusters of papillary and acini structures within the lungs. They rarely metastasise. JSRV has its own oncogene which causes a cell to become neoplastic.

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26
Q

Describe Squamous Cell Carcinoma

A

This is malignant neoplasm of squamous epithelium. It can be found in different organs including the skin, oral cavity, larynx, oesophagus, stomach, urinary tract, penis and vulva. They are locally invasive and do metastasise, usually to the draining lymph nodes. They are nodular, proliferative and sometimes ulcerated lesions. Histologically they are made up of cords or whorls of pleomorphic epithelial cells. Sometimes they have keratin pearls at the centre o f the whorls. They are normally found on nonpigmented or sparsely haired skin, as UV light is an important cause of genetic damage to epithelial cells.

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27
Q

Describe Feline Vaccine Associated Sarcoma

A

This neoplasm occurs at vaccine sites in cats, in the interscapular region and lateral thorax. The neoplasms can be fibroblastic, myoblastic, chondroblastic, or osteoblastic. They are malignant, spread into surrounding tissue and can metastasise. They can b e very difficult to remove from interscapular region.

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28
Q

What is the Tasmanian Devil facial tumour?

A

Malignant neoplasms were found on the face and mouth of Tasmanian devils, they consisted of poorly differetiated highly pleomorphic, malignant schwann cells. The neoplasm seemed to be transmitted between devils. (an allograft). The tumour cells from another animal were not being recognised as non self - may be because Tasmanian devils lack genetic diversity and have very similar MHCs.

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29
Q

What are the effects of the Renin-angiotensin and aldosterone system?

A

Main role is in maintaining the Effective circulating volume. Renin is produced by specialised juxtaglomerular cells in the glomerular afferent arteriole. Renin is released in response to decreased renal perfusion due to decreased blood pressure and decreased volume. Renin converts angiotensinogen to angiotensin I which then converts to angiotensin II. Angiotensin II increases aldosterone production by the adrenal cortex and enhances renal Na absorption.

30
Q

Describe the effects of increased blood hydrostatic pressure

A

If increased, oedema may arise. Oedema may be generalised or localised due to focal obstruction. Generalised is usually the result of cardiac failure which leads to an increase in venous pressure. Left sided failure causes pulmonary congestion and pulmonary oedema. Right sided failure causes systemic congestion and generalised oedema. The failing heart fails to keep up with blood being returned to it.

31
Q

Describe oedema caused by increased vascular permeability.

A

This is really the oedema of inflammation - fundamental to this mechanism is the opening of inter endothelial gaps allowing leakage of plasma proteins as well as inflammatory cells. This oedema has a higher protein content than the other forms.

32
Q

Describe oedema caused by decreased plasma colloidal pressure

A

This is a measure of the ability of colloidal solutes to draw water towards them. The most important is albumin. Decreased plasma colloid osmotic pressure is usually due to hypoalbuminaemia. hypoalbuminaemia usually results from inadequate albumin production or loss of albumin from kidney or Gi tract.

33
Q

Describe Haemodynamic pulmonary oedema.

A

This is usually due to increased hydrostatic pressurer, typically secondary to left heart failure and backing up of blood in the pulmonary vein and then pulmonary capillary bed.

34
Q

Describe Microvascular Injury pulmonary oedema.

A

This is when the capillaries in the pulmonary vascular bed are damaged. Typically the endothelial cells are damaged and hydrostatic pressure is normal. The pathogenesis of pulmonary oedema, regardless of cause, tends to follow this sequence: Fluid exceeds lymphatic drainage accumulates in interlobular septa, alveolar walls fill with fluid, alveolar spaces fill with fluid.

35
Q

What is hyperaemia?

A

Hyperaemia occurs when arteriolar dilation increases blood flow to a tissue an active process which leads to tissue erythema.

36
Q

What is congestion?

A

Congestion is due to reduced outflow of blood from a tissue (a passive process). Chronic vascular congestion can contribute to the development of oedema.

37
Q

Describe the process of haemostasis and fibrinolysis

A

Vascular Injury - arteriolar vasoconstriction followed by platelet adherence and activation.
Activated Platelets - change from small rounded discs to flat plates to increase surface area. Tissue factor aka factor III is exposed at the point of vascular injury. This procoagulant glycoprotein acts to initiate coagulation cascade. Thrombin converts fibrinogen into fibrin.Forms a plug. Activation of coagulation cascade simultaneously activates the fibrinolytic cascade.

38
Q

What is thrombocytopenia?

A

Decreased platelet numbers - may be due to decreased production or increased destruction/utilisation of platelets.

39
Q

What is thrombus?

A

A thrombus is a layered mass containing red blood cels, granular leucocytes and platelets held together by fibrin. The process by which it is formed is known as thrombosis.

40
Q

What is the difference between an antemortem thrombus and a postmortem clot?

A

An antemortem thrombus is granular dry, dull, firm, white or cream/red/pink, attached to vessel wall or chordae tendinae in heart. A postmortem clot is smooth, moist, shiny, elastic, homogenous, dark red, conforms to vessel and is not adherent.

41
Q

What is an embolus?

A

A solid or gaseous mass carried by the bloodstream from its point of origin to a distant site within the circulation. This process is called embolism - stops when it arrives at a blood vessel of smaller diameter than itself.

42
Q

What is Cardiogenic shock?

A

This results from failure of the heart to adequately pump blood. Possible causes include myocardial infarct, arrhythmias etc. Stroke volume and cardiac output decrease and the compensatory mechanisms cannot cope, leading to stagnation of blood and tissue hypoxia.

43
Q

What is Hypovolaemic shock?

A

This is due to reduced circulating volume resulting from blood loss or fluid loss. Haemorrhage, vomiting diarrhoea or burns. This leads to hypotension and hypoperfusion. Some initial compensation protects the kidneys heart and brain.

44
Q

Describe shock due to Blood maldistribution?

A

This is characterised by decreased peripheral vascular resistance and pooling of blood in peripheral tissues. It is usually caused by neural or cytokine induced vasodilation and potential causes include trauma, hypersensitivity and endotoxaemia. Blood volume remains normal but microvascular area increases substantially so ECV reduces. Three main types - Neurogenic, anaphylactic and septic shock.

45
Q

Describe Neurogenic Shock

A

Usually induced by trauma, generally to the nervous system, electrocutin, fear, emotional stress. Autonomic discharges > vasodilation > venous pooling.

46
Q

Describe Anaphylactic shock?

A

Generalised type I hypersensitivity commonly caused by insect or plant allergens, drugs or vaccines. The inciting substance interacts with IgE bound to mast cells > widespread mast cell degranulation > release of histamine > systemic vasodilation and increased vascular permeability > hypotension and hypoperfusion.

47
Q

Describe septic shock.

A

This is the most common form of shock due to maldistribution. It is mediated by vascular and inflammatory mediators released in response to bacteria or fungal elements. The most common cause is endotoxin, a LPS in the cell wall of gram negative bacteria. LPS is a pattern associated molecular pattern. It binds to CD14 and TLr4. Causes the activation of macrophages, Activation of factor XII > coagulation.

48
Q

What characterises a granulomatous disease?

A

Granulomatous diseases are characterised by granulomatous inflammation. This is inflammation in which macrophages predominate. Granulomatous diseases are usually caused by irritants or agents that are persistent and not easily degraded by macrophages.

49
Q

What is the difference between a granuloma and granulomatous disease?

A

Some but not all granlomatous diseases cause granulomas. Granulomas are focally discrete, closely packed aggregates of macrophages. Classical granulomas consist of focally discrete closely packed aggregates of macrophages surrounded by a zone of lymphocytes and an outer rim of fibroblasts.

50
Q

What are the cells present in granulomatous disease?

A

Granulomatous disease - macrophages predominate, also giant cells and lymphocytes.
Eosinophilic granulomatous disease - macrophages plus eosinophils. Pyogranulomatous disease - macrophages plus neutrophils.

51
Q

Describe how bacteria can cause granulomatous disease

A

Bacteria that have the ability to survive inside macrophages cause granulomatous diseases such as mycobacteria, salmonella, rhodococcus.

52
Q

Describe other aetiology of granulomatous diseases?

A

Parasites - most tissue invasive parasites elicit a granulomatous response. Fungi, Viruses - viruses do not often cause granulomatous inflammation - two examples are feline coronavirus and porcine circovirus, foreign material, toxins, idiopathic.

53
Q

What is feline infectious peritonitis?

A

FIP is caused by the coronavirus feline infectious peritonitis virus. FIPV is very closely related to feline enteric corona virus. Most cats are asymptomatically infected with FECV. In some cats the 3c gene mutates and virus becomes FIPV. It can now enter and replicate in macrophages.

54
Q

What is Porcine Circovirus?

A

Porcine circovirus 2 causes a number of different diseases which are classified as PCV-2 associated diseases (PCVAD). One of the key features is not all pigs develop disease. Most common PCVADs is post weaning multisystemic wasting syndrome (PMWS). - weight loss, jaundice, difficulty breathing. Granulomatous lesions in lymph nodes, liver, etc. Porcine dermatitis and nephropathy syndrome is another.

55
Q

Describe how foreign material can cause granulomatous disease.

A

Most foreign material will induce a granulomatous response as it is difficult to impossible for macrophages to breakdown/phagocytose it, eg suture material, silica, feed dust. hair shafts, aspiration pneuomonia.

56
Q

Describe an idiopathic granulomatous disease?

A

Granulomatous meningoencephalomyelitis is an idiopathic disease which causes granulomatous disease in the CnS of small breed dogs and causes neurological signs. There are few lesions grossly, histologically there is inflammation and necrosis of the white matter with many macrophages, lymphocytes and plasma cells present.

57
Q

What is Mycobacteria and how does it cause granulomatous disease?

A

Mycobacteria have a very specialised cell wall which allows them to survive inside phagosomes within cells. Once the bacteria is within macrophages an efficient cell mediated immunity is needed to keep it suppressed. A granuloma forms and walls off the infection. Infection can reactivate, the granuloma fails to wall off infection and the bacteria can spread.

58
Q

What are the causes of neoplasia?

A

A single inherited mutated gene, multiple inherited genes, acquired somatic mutations. Causes of the acquired somatic mutations may be intrinsic factors - reactive oxygen species, DNA polymerase errors, or extrinsic factors - chemicals, radiation, viruses.

59
Q

What are the main routes a neoplasm can metastasis?

A

Haematogenous, lymphatic, transcoelomic - seeding body cavities.

60
Q

What are the direct effects of neoplasia?

A

Compress tissue, compress blood vessels, block tubular structures, organ rupture, haemorrhage, tumour emboli leading to infarcts.

61
Q

What is the bodies immunity against neoplasia?

A

Includes CD8+ Cytotoxic lymphocytes, NK cells, macrophages.

62
Q

what are are the molecular determinants of neooplasia?

A

Growth promoting oncogenes - Ras
Growth inhibiting tumour suppressor genes - p53, RB, APC
Apoptosis genes - P53
DNA repair genes - BRCA.

63
Q

What is angiogenesis?

A

The formation of new blood vessels. Neoplasms can’t grow more than 1-2mm diameter without a blood supply. Neoplastic cells alter the balance between pro angiogenic and anti angiogenic substances to promote blood vessel growth.

64
Q

Describe Canine mast cell tumours.

A

One of the most common neoplasms of the skin. Occurs in the dermis and subcutaneous tissues. Probably a result of multiple cumulative genetic changes. Mutations in one gene - the c kit gene are very common. C-kit gene encodes for the KIT protein. KIT is a cell surface growth factor which signals cells to proliferate.

65
Q

Describe how a bronchoalveolar lavage/transtracheal wash/pleural peritoneal or synovial fluid sample would be collected.

A

BAL/TTW, pleural, peritoneal and synovial fluid are submitted in an EDTA tube for cytology and cell counts, plus a plain sterile tube for microbiology and biochemistry. Make smears as well.

66
Q

How are urine samples collected for cytology?

A

Submitted in a sterile universal contained for routine analysis but place a sample in EDTA if cytology is required. Dipstick tests should be carried out on the whole urine. Wet preps will detect RBCs, WBCs, Crystals, casts, bacteria, fat droplets etc. Dried smears from the ETA sample are made for cytology if inflammation or abnormal cells are suspected.

67
Q

What are skin scrapings used for?

A

Used for the same samples as impression smears but collect more cells. Suitable for rapid diagnosis of some external lesions and excised tissues which may subsequently be examined by histopathology. Also used for parasitology. Use a scalpel perpendicular to the skin.

68
Q

What are fine needle aspirates used for?

A

Suitable for cutaneous masses, internal masses and organs, lymph nodes etc. Avoids superficial contamination and collects samples from deep within the lesion/tissue. There is a risk of coming out of small lesions or missing them altogether.

69
Q

What are swabs used for?

A

Suitable for tissues which are not readily reached e.g vagina, fistulous tracts, use cotton swab moistened in 0.9NaCl. Roll swab down middle of the microscope slide.

70
Q

What are the uses of Diff-Quik Staining?

A

Ideal for in house haematology and cytology. Does not stain some granules in cell walls, especially mast cell granules. It is easier to examine slides if you coverslip them by placing a few drops of DPX mounting fluid on the cover slip, inverting the slide on top to pick up the cover slip, placing it the right way up again on the bench and letting the coverslip dry on.

71
Q

What is a cyst?

A

Contains fluid and few cells e.g sweat gland cyst, prostatic cyst. The fluid is usually low in protein, with a small number of cells, often with reactive macrophages predominating.

72
Q

Describe the criteria of malignancy.

A

Pleomorphism - variable size, shape and nucleus.
Anisocytosis, macrocytosis - marked variation in cell size
Hypercellularity - increased cell exfoliation
Disordered alignment of the cells in clusters

73
Q

Describe the criteria of malignancy of the Nucleus

A

Anisokaryosis - marked variation in nuclear size
Macrokaryosis - increased nuclear size
Increased nucleus: cytoplasm ratio - >1:2 (normal in lymphoid tissue). Multinucleation - multiple nucleation in a cell, especially important if nuclei vary in size. (exception - osceoclasts)