Mechanisms of disease Flashcards

Question

In a lung suffering from a pulmonary embolism, what colour will the tissue be?

Answer 1

It will be red. The lung has a dual blood supply. Occlusion of the main blood supply causes an infarct. The collateral arterial supply is insufficient to rescue the tissue but does allow blood to enter the dead tissue creating a red infarct. Also the lung has loose stroma which allows bleeding to occur into the infarct.

Answer 2

Immune thrombocytopenic purpura – an idiopathic condition that presents with a purpuric rash and low platelets. Patients produce autoantibodies against platelet membrane glycoproteins. The onset is abrupt but often preceded by a viral illness. It usually resolves spontaneously in 6 months.

Answer 3

Carcinoembryonic antigen (CEA).

Answer 4

**Formation of adhesions** : Compromising organ function or blocking tubes, e.g., intestinal obstruction following abdominal surgery **Loss of function:** Due to replacement of specialised functional parenchymal cells by scar tissue, e.g., healed myocardial infarction with non-contracting area of myocardium

Answer 5

**_VASOACTIVE AMINES_** **Histamine**: Mast cells, basophils + platelets **Serotonin (5-HT)**: Platelets **_VASOACTIVE PEPTIDES_** **Bradykinin:** From plasma precursor kininogen**,** causes: ↑ vascular permeability, dilatation of blood vessels and pain **Prostaglandins:** From membrane phospholipids by cyclo-oxygenase, vasodilatation **Factors from neutrophils and platelets:** C3a, C5a, IL-1, f

Answer 6

It is characterised by activation of coagulation resulting in formation of microthrombi in the microcirculation. There is consumption of clotting factors and platelets and activation of fibrinolysis. This in turn leads to haemorrhage. The following processes come into play: * Microthrombi formation causing tissue ischaemia . * Haemorrhage – this may be very severe and is seen from mucous membranes and into the skin or internal organs including the brain. * Microangiopathic haemolytic anaemia – as red blood cells squeeze through vessels narrowed by microthrombi.

Answer 7

The media of the aorta is weakened by atheroma and no longer has elastic recoil as elastin fibres are destroyed by atherosclerosis. Laplace’s law – for a given pressure, increased radius requires increased wall thickness to accommodate a stable wall tension.

Answer 8

**1. Pyrexia** - Bacterial endotoxins - Pyrogenic cytokines, e.g. TNF, IL-2, from macrophages and neutrophils, act on anterior hypothalamus, ↑ synthesis of prostaglandin E2 (why aspirin reduces fever) **2. Leucocytosis** (↑ WCC) – Macrophages + endothelial cells release colony-stimulating factors so BM produces more leucocytes – IL-1 and TNFa accelerate release from BM – Bacterial infections = ↑neutrophils – viral = ↑lymphocytes **3. Acute phase response in liver** Constitutional symptoms (malaise, anorexia, nausea) – acute phase proteins: fibrinogen, CRP (C-reactive protein), alpha1 antitrypsin, Haptoglobin, Serum amyloid A protein – reduced protein synthesis **4. Shock** = circulatory failure (clinical syndrome) • Due to spread of microorganisms and toxins (septic shock). Often fatal

Answer 9

**Lobar pneumonia** affects all or part of a lobe with other areas generally normal. **Bronchopneumonia** is especially seen in young and old patients. It has a patchy distribution and generally involves more than one lobe.

Answer 10

1. Single node/groups 2. Two or more groups on the same side of the diaphragm 3. Disease both sides of the diaphragm 4. Involvement of extralymphatic organs, e.g. liver, lung, bone marrow

Answer 11

* Epidermal growth factor * Vascular endothelial growth factor * Platelet-derived growth factor * Granulocyte colony stimulating factor

Answer 12

Underproduction or malproduction of LDL clearance receptor in the liver.

Answer 13

Defective conversion of procollagen to tropocollagen

Answer 14

**Cervical Screening** - 25-64 year old women **Breast Screening** - 50 -70 year old women every 3 years **Bowel Cancer Screening** - 60-69 year old men and women. **Bowel scope screening programme** - 55 year olds

Answer 15

Gastric adenocarcinoma. MALT (mucosa associated lymphoid tissue) lymphoma.

Answer 16

A growth, usually benign, with a stalk, protruding from a mucus membrane.

Answer 17

ROLLING: **selectins** expressed by endothelial cells bind to carbohydrate ligands (sLex) on neutrophils. Increased by several cytokines secreted by macrophages, mast cells and endothelial cells e.g. **IL-1** and **TNF** ADHESION: **integrins** expressed by neutrophils bind to integrin ligands on the endothelium. **C5a**, **leukotriene** **B4**, **IL-1** and **TNF** increase expression. DIAPEDESIS: **chemotaxins** e.g. **C5a**, leukotriene **B4**, bacterial peptides stimulate neutrophils to migrate through the inter-endothelial cell junctions

Answer 18

1. Denaturation of intracellular proteins 2. Enzymatic digestion by lysosomes inherent to the dying cell and lysosomes of leukocytes that are part of the inflammatory reaction

Answer 19

The clinical term used to describe visible necrosis. May be wet, dry, or gaseous

Answer 20

Fibroblasts that develop a contraction phenotype. They resemble smooth muscle cells and are intermediate between fibroblasts and smooth muscle cells. They contract and help close the wound

Answer 21

* Potent inducer of blood vessel development (vasculogenesis) and role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing

Answer 22

**Vascular** **spasm** **Primary** **haemostasis** - formation of unstable platelet plug **Secondary** **haemostasis** - stabilisation of plug with fibrin (blood coagulation system) Dissolution of clot and vessel repair **(fibrinolysis)**

Answer 23

A process for taking a biopsy of the endometrium using a plastic tube (the pipelle ) inserted through the cervical os and which uses suction to obtain endometrial tissue.

Answer 24

Neutrophils migrate to site of injury by chemotaxis Phagocytose and kill microorganisms Eliminate foreign material and necrotic tissue Produce growth factors for repair

Answer 25

Bloom-Richardson grading system which assesses tubule (glandular) formation, nuclear pleomorphism and mitotic rate within the tumour, i.e. how well differentiated the tumour is.

Answer 26

Retains stains even on treatment with a mixture of acid and alcohol.

Answer 27

altered adhesion, stromal proteolysis and motility

Answer 28

Gleason grading – based on the pattern of glandular differentiation.

Answer 29

Adenocarcinoma

Answer 30

Swelling of the cell

Answer 31

* Local mediators involved in cell proliferation * Coded by proto oncogenes * Polypeptides that act on the cell surface * Local hormones * They stimulate cell proliferation but may also affect cell locomotion, contractility, differentiation and angiogenesis.

Answer 32

Considerable wound contraction must take place to close wound Substantial scar formation, new epidermis often thinner than usual Takes longer than healing by primary intention

Answer 33

**Endothelial cell contraction:** Chemical mediators e.g. histamine, C5a, NO **Endothelial cell injury:** Direct e.g. trauma, chemicals, microbial toxins or ndirect e.g. toxic oxygen species and proteolytic enzymes from neutrophils **Structural** **re-organisation** **of** **cytoskeleton****:** Cytokine mediated e.g. interleukin-1, TNF **Transcytosis**: VEGF induces ↑ channels in endothelial cells

Answer 34

Variation in size and shape, occurs in neoplastic cells and nuclei.

Answer 35

Lack of differentiation (‘to form backwards’).

Answer 36

* Detachment of tumour cells from one another by unzipping of the anchor protein E-cadherin. * Degradation of the extracellular matrix by collagenase attacking the collagen fibres of the basement membrane * Loss of adhesion of cells from integrins: this process should induce apoptosis but fails to in tumour cells. * Migration of tumour cells through the extracellular matrix.

Answer 37

Inflammation is limited to mucosa and submucosa Crypt abscesses common Distorted crypt architecture very common Significant increased risk of colon cancer Often most severe in distal colon Colectomy often indicated

Answer 38

Pyrexia Leucocytosis (↑ WCC) Acute phase response in liver Shock = circulatory failure (clinical syndrome)

Answer 39

1. Formation of primary haemostat plug 2. Platelets adhere to subendothelial structures via von Willebrand factor (VWF) 3. adhere to each other (aggregation) 4. form a platelet plug held to together by insoluble fibrin

Answer 40

It is an initiator and a promoter (it is proinflammatory). It generates free radicals. It absorbs toxic elements onto the fibres.

Answer 41

pkynosis karyorrhexis karyolysis

Answer 42

Hypertrophy of granulation tissue that grows above the surface of the surrounding skin and blocks reepithelialisation . It is treated by cautery or surgical removal.

Answer 43

1. Neutrophils migrate to site of injury by chemotaxis 2. Phagocytose and kill microorganisms 3. Eliminate foreign material and necrotic tissue 4. Produce growth factors for repair 5. Activated neutrophils may release toxic metabolites and enzymes causing damage to normal host tissue

Answer 44

* Stored in platelet alpha granules and released on platelet activation * Also produced by macrophages, endothelial cells, smooth muscle cells and tumour cells * Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes

Answer 45

Dukes staging for colorectal cancers Ann Arbor staging for lymphomas

Answer 46

1. Rare type of cancer that usually affects the bones of children and adolescents – **Ewing’s sarcoma** 2. Benign tumour of cartilage – **chondroma** 3. Often produces CEA – **colon cancer** 4. Commonest cause of cancer death in the UK – **lung cancer** 5. Has a known association with Aspergillus flavus – **hepatocellular carcinoma** 6. Tumour that can produce 5HT – **carcinoid tumour** 7. Tumour that is usually benign in the ovary and malignant in the testis – **teratoma** 8. Associated with EBV – **Burkitt’s lymphoma** 9. Malignant tumour of blood vessels – **angiosarcoma** 10. A cancer of the skin that rarely metastasises – **basal cell carcinoma** 11. Malignant tumour of skeletal muscle – **rhabdomyosarcoma** 12. Benign tumour of melanocytes – **naevus** 13. Produces vanillyl mandelic acid – **phaeochromocytoma** 14. Another name for nephroblastoma – **Wilm’s tumour** 15. Tumour, often within the skin and frequently associated with HIV infection – **Kaposi’s sarcoma** 16. Tumour of the thyroid gland that can produce calcitonin - **medullary carcinoma** 17. Common tumour of the bladder– **transitional cell carcinoma** 18. Associated with asbestos exposure – **malignant mesothelioma** 19. Often produces human chorionic gonadotropin – **choriocarcinoma** 20. Type of lung tumour most often associated with ectopic production of ADH – **small cell carcinoma**

Answer 47

It is the increased risk of thromboembolism in disseminated cancers. It occurs as tumours produce inflammation and tissue injury causing release of procoagulants. Some also produce and release mucin which is also a procoagulant.

Answer 48

are abnormally activated versions of normal genes called proto-oncogenes. Only one allele of each proto-oncogene needs to be activated to favour neoplastic growth.

Answer 49

Healing by first intention - the healing that is seen in a clean wound opposed by sutures. The wound consists of a narrow space and there is limited epithelial and soft tissue destruction.

Answer 50

1. Ectopic secretion of PTH-related protein in a paraneoplastic syndrome: * Paraneoplastic syndrome = a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumour cells or by an immune response against a tumour. * Seen in carcinomas of breast, lung (especially squamous cell bronchogenic carcinoma), kidney and ovary. • = humoral hypercalcaemia of malignancy. 2. Destruction of bone tissue: * Primary tumours of bone, e.g. multiple myeloma, leukaemia. * Diffuse skeletal metastases, e.g. breast cancer.

Answer 51

Aspirin / NSAIDs e.g. naproxen, meloxicam Antihistamines Corticosteroids Leukotriene antagonists e.g. Montelukast TNF alpha antagonists e.g. Infliximab

Answer 52

* Inactive enzymatic proteins (e.g. C3a, C5a) made in liver, present in blood * Activated by variety of mechanisms: proteolytic enzymes from necrotic cells, anitgen-antibody complexes in infection, gram -ve bacterial (classic and alternate pathways, respectively) and by products of kinin and fibrinolytic systems.

Answer 53

Healing with the formation of fibrous connective tissue.

Answer 54

Serum calcium concentration and serum angiotensin converting enzyme (ACE) levels are both raised in sarcoidosis.

Answer 55

Triple negative cancers do not express oestrogen receptor (ER), progesterone receptor (PR) or Her2 receptors. Therefore, these cancers do not respond to endocrine treatment or treatment with Herceptin (trastuzumab). However, they often show a better response to chemotherapy than some other breast cancers.

Answer 56

i. Loss of the electron transport chain (inner mitochondrial membrane) ii. Cytochrome C leaking into cytosol (activates apoptosis)

Answer 57

Because collateral venous channels open up to aid circulation.

Answer 58

tumours arise from precursor cells and are composed of cells with immature characteristics seen in developing (embryonic) stages. Generally a tumour of infants /children. eg nephroblastoma, neuroblastoma, pulmonary blastoma, retinoblastoma

Answer 59

degradation of tissue by enzymes

Answer 60

Langhans type giant cells – seen in tuberculosis. Touton giant cells – seen in lesions containing a lot of fat. Foreign body giant cells – generated in response to the presence of a large foreign body

Answer 61

An apoptotic cell (also called Councilman bodies in the liver).

Answer 62

protein denaturation

Answer 63

**Haematoma**: fills gap and surrounds injury **Granulation tissue forms**: cytokines activate osteoprogenitor cells **Soft callus:** at 1 week, fibrous tissue and cartilage within which woven bone forms **Hard callus**: after several weeks, initially woven bone –weaker and less organised than lamellar bone but can form quickly **Lamellar bone:** replaces woven bone, remodelled to direction of mechanical stress, bone not stressed is resorbed and outline is re-established

Answer 64

Respiratory compromise – there is a non-perfused but ventilated area of lung, i.e. a ventilation-perfusion mismatch which results in hypoxaemia. Haemodynamic compromise – there is an increased resistance to pulmonary blood flow due to obstruction of the pulmonary vessels by the embolus. This results in acute right sided heart failure (acute cor pulmonale).

Answer 65

* **Vasodilatation**: histamine, prostaglandins, bradykinin, NO * **Increased vascular permeability**: histamine, bradykinin, C5a + C5b, NO leukotrienes * **Neutrophil chemotaxis, recruitment and activation**: C5a, LTB4, bacterial peptides * **Phagocytosis**: Fc (e.g. IgG antibody) and C3b = opsonins * **Fever**: IL-1, TNF, prostaglandins * **Itching + Pain**: bradykinin, serotonin and prostaglandins

Answer 66

**Lymphocytes** – specific immune response, cytokine production. **Macrophages** – phagocytosis, cytokine production. **Plasma cells** – antibody production.

Answer 67

Tamoxifen is one of a class of drugs called selective oestrogen receptor modulators (SERMS). It is antioestrogenic and used to treat women who have had oestrogen receptor positive breast cancers. In these tumours it antagonises the oestrogen receptor and blocks the proliferative action of oestrogen. However, within the endometrium, tamoxifen has some oestrogenic activity and acts as an agonist at oestrogen receptors (as it acts as an antagonist at some receptors and an agonist at others it is a partial agonist). It can therefore cause endometrial hyperplasia.

Answer 68

**Skin** – erythema nodosum, pyoderma gangrenosum. **Liver** – pericholangitis , sclerosing cholangitis, hepatitis, cirrhosis. **Eye** – iritis, uveitis, episcleritis. **Joints** – ankylosing spondylitis, arthritis

Answer 69

Characterised by the microscopic appearances which are much more variable than acute inflammation. Granulation tissue.

Answer 70

Coagulative necrosis.

Answer 71

Malignant tumour of plasma cells.

Answer 72

* Endometrial hyperplasia and endometrial carcinoma. * Increased risk of DVT and PE.

Answer 73

Limited calf muscle contraction during immobility which reduces the milking action of the calf muscles. This leads to stasis of blood within the veins and then thrombosis. This may be compounded by other risk factors such as smoking, obesity, pregnancy, the oral contraceptive pill, and dehydration (which can be induced by drinking alcohol).

Answer 74

destruction to adipocytes as a consequence of trauma or secondary release of lipases from damaged pancreatic tissue

Answer 75

Chronic inflammatory synovitis. Erosion of articular cartilage.

Answer 76

Polypeptide alpha chains synthesised in ER of fibroblasts and myofibroblasts Enzymatic modification steps including vitamin C dependent hydroxylation Alpha chains align and cross-link to form procollagen triple helix Soluble procollagen is secreted After secretion procollagen cleaved to give tropocollagen Tropocollagen polymerises to form microfibrils and then fibrils

Answer 77

deposits of "immune complexes" together with fibrin that has leaked out of vessels

Answer 78

1. Changes in blood flow - ↑ blood flow 2. Exudation of fluid into tissues 3. Infiltration of inflammatory cells **1 and 2 = Vascular phase 3 = Cellular phase**

Answer 79

**1. Congestion** – the lobe is heavy, red and boggy. There is vascular congestion. Proteinaceous fluid, scattered neutrophils and many bacteria are present in the alveoli. **2. Red** **hepatisation** – occurs after a few days. The affected lung has a liverlike consistency. The alveolar spaces are packed with neutrophils, red cells and fibrin. There is a fibrinous or fibropurulent exudate (pus) on the adjacent pleura. **3. Grey** **hepatisation** – the lung tissue is dry, grey and firm. Red cells get lysed, fibrous exudate persists within alveoli. **4. Resolution** – the exudate is enzymatically digested and resorbed or expectorated. The basic architecture of the lung is left intact.

Answer 80

Women aged between 47 and 73 years. They are screened with two view mammograms (x-rays of the breast). Every three years.

Answer 81

Progression through the cell cycle, and particularly the G1/S transition, is tightly regulated by proteins called cyclins and associated enzymes called cyclin-dependent kinases (CDKs). CDKs become active by binding to and complexing with cyclins.

Answer 82

A **hypertrophic scar** is a raised scar but one that doesn’t grow beyond the boundaries of the original wound. It can regress. A **keloid scar** grows beyond the edges of the wound and doesn’t regress.

Answer 83

A calcified tuberculous granuloma in the lung.

Answer 84

amorphous debris surrounded by histocytes resulting in granulomatous formation

Answer 85

Healing by secondary intention.

Answer 86

Paralysis of one side of the body

Answer 87

We measure blood levels of intracellular macromolecules that leak out of fatally injured myocardial cells through damaged cell membranes. Now we measure primarily cardiac troponin T (TnT). Other proteins that can be measured are troponin I (TnI), creatine kinase (CK, CK-MB), lactate dehydrogenase (LDH) and myoglobin. Troponins are proteins that regulate contraction of muscle. They are increased in the blood at 2-4 hours post-MI and peak at 48 hours. They remain elevated for 7-10 days

Answer 88

A common form of intracranial aneurysm, they are congenital or secondary to blood vessel injury. They commonly occur within the circle of Willis and the adjacent arteries. After rupture, the blood accumulates in the subarachnoid space.

Answer 89

growth factor withdrawal loss of matrix attachment glucocorticoids viruses free radicals ionising radiation

Answer 90

* The cells must degrade basement membrane and stroma to invade. This involves altered expression of proteases, notably **matrix metalloproteinases (MMPs).** * Malignant cells take advantage of nearby non-neoplastic cells, which together form a **cancer niche**. * These normal cells provide some growth factors and proteases. * Altered motility involves changes in the actin cytoskeleton. Signalling through integrins is important and occurs via small G proteins such as members of Rho family.

Answer 91

This is broadly based on how a tumour resembles its parent tissue.

Answer 92

Usually X-linked disease, therefore patients usually male Type IV collagen abnormal Dysfunction of glomerular basement membrane, cochlea of ear and lens of eye Presents with haematuria in children/adolescents progressing to renal failure

Answer 93

Peripheral fat converts adrenal androgens to oestrogens and therefore obese women have higher levels of serum oestrogens than thinner women. High levels of oestrogen cause proliferation of the endometrium.

Answer 94

1. Vascular stasis causes neutrophils to line up along endothelium = **MARGINATION** 2. Roll along endothelium = **ROLLING** 3. Stick avidly to endothelium = **ADHESION** 4. Emigrate through the endothelium= **MIGRATION / DIAPEDESIS**

Answer 95

Men and women aged 60-69 years, every two years.

Answer 96

Rheumatoid nodules. There is fibrinoid necrosis surrounded by a giant cell granulomatous reaction.

Answer 97

Full blood count (platelets) **Prothrombin time (PT)** - measures the EXTRINSIC PATHWAY (factors VII, X, V, II and fibrinogen) **Activated partial thromboplastin time (APTT)** - measures the INTRINSIC PATHWAY (factors I (fibrinogen), II (prothrombin), V, VIII, IX, X, XI and XII. ).

Answer 98

1. soft 2. gelatinous 3. deep red - deoxygenated 4. higher cell content

Answer 99

Dysplasia is a precancerous condition: cells which are very similar to cancer cells grow in an organ but have not yet acquired the ability to invade into tissue or metastasize

Answer 100

* **C3b** that functions as an opsonin * **C5a** that attracts neutrophils. * **C5-9** **complex** ("membrane attack complex”) that attaches to the cell causing lysis by cell membrane perforation.

Answer 101

Fatty liver, also known as fatty liver disease (FLD), is a REVERSIBLE condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis.

Answer 102

There is myocyte hypertrophy but no increase in capillary numbers, therefore there is increased oxygen demand but no increase in oxygen supply. This results in relative anoxia. Also there is often deposition of fibrous tissue (interstitial fibrosis) in the myocardium in ventricular hypertrophy and this can cause arrhythmias and cardiac failure.

Answer 103

Atrophy is the shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells. i. Involution is the normal programmed shrinkage of an organ, e.g. during embryogenesis ii. Hypoplasia is the congenital underdevelopment or incomplete development of an organ

Answer 104

Repeated obstruction by gall stones Repeated acute inflammation leads to chronic inflammation Fibrosis of gall bladder wall Chronic inflammatory cells

Answer 105

**Oxygen-dependent** – Oxygen derived free radicals are released into the phagosome – Toxic oxygen species (Superoxide) is converted to hydrogen peroxide by myeloperoxidase from neutrophil granules (H2O2-myeloperoxidase-halide system –\> hypochlorite) – Oxygen or respiratory burst **Oxygen-independent** – Enzymes e.g. lysozyme, protease, nuclease, phospholipase from neutrophil granules can form holes in microbial membranes

Answer 106

Sepsis is the body’s overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure, and death. In other words, it’s your body’s over active and toxic response to an infection

Answer 107

Ascending cholangitis – the bile duct becomes inflamed usually as a result of biliary obstruction complicated by bacterial infection. The bacterial infection can then spread into the liver where an abscess forms.

Answer 108

Polycyclic aromatic hydrocarbons, e.g. benzo[a]pyrene are most often implicated.

Answer 109

More than 90% are due to Streptococcus pneumoniae.

Answer 110

1. Iron deficiency due to chronic external haemorrhage (hypochromatic, microcytic). 2. Anaemia of chronic disease: • Low serum iron and low erythropoietin secondary to cytokine production. • Normocytic and normochromic or hypochromic and microcytic. • There is normal stored iron. 3. Myelophthisic anaemia – seen with space occupying lesions that destroy bone marrow. 4. Aplastic anaemia secondary to irradiation or drugs. 5. Megaloblastic anaemia secondary to folate acid antagonists (antimetabolites). 6. Immunohaemolytic anaemia secondary to reaction to tumour or drugs.

Answer 111

**Antithrombin III** - serine protease inhibitor - Inhibits thrombin and 10a **Protein C** - Vit K dependent zymogen, activated into serine protease by thrombin binding to endothelial receptor thrombomodulin - Cleaves co factors Va and VIIIa - Protein S is a co factor of Protein C

Answer 112

A screening test for tuberculosis. It is a delayed hypersensitivity reaction where purified Mycobacterial tuberculosis protein derivative is injected intradermally. 48-72 hours later patients who have been exposed to the bacteria develop a delayed hypersensitivity reaction seen as inflammation in the dermis.

Answer 113

Fever, night sweats, weight loss. They indicate a worse prognosis.

Answer 114

A lesion that occurs after a nerve has been severed when there is poor alignment of the cut ends of the nerve or if distal tissue has been amputated. It is the result of a disordered proliferation of axons which results in a tangled mass of axons. It can cause a painful nodule.

Answer 115

A malignant tumour of cells lining the pleura, peritoneum or pericardium.

Answer 116

The clot dries and forms a scab. The scab contracts as it dries and shrinks. Granulation tissue forms and contracts. The epidermis regenerates and grows in from the sides and then from the base up. There is fibrous repair of the dermis. The scar matures.

Answer 117

Patients develop (at birth or soon after) 500-2,500 colonic adenomas that carpet the mucosal surface. May also have polyps elsewhere in the gastrointestinal tract, e.g. ampulla of Vater, stomach. Most polyps are tubular adenomas. Progression to colon cancer occurs in approximately 100% of patients by the age of 50 years. The disease needs early detection and prophylactic colectomy – also in siblings and first degree relatives

Answer 118

A venous embolus that causes systemic artery infarction by passing through an interatrial in interventricular defect

Answer 119

A neoplasm is “An abnormal growth of cells that persists after the initial stimulus is removed”

Answer 120

defect in Factor VIII FVIII (‘antihaemophilic factor’) not a protease, but stimulates the activity of FIXa, a serine protease. Normal activity of FVIII increased by proteolysis by thrombin and FXa. Positive feedback amplifies clotting signal, accelerates clot formation. Reduced/absent FVIII results in reduced/absent clotting and prolonged bleeding. **Treatment with recombinant FVIII**

Answer 121

Should have a suppressive effect on tumour growth as it acts as an antagonist at the oestrogen receptor (ER) and decreases cell replication.

Answer 122

They form by fusion of macrophages. They arise as a result of frustrated phagocytosis

Answer 123

keratinocytes Actinic keratosis

Answer 124

Patient information - hydration and early mobilization Risk assessment for VTE and bleeding Anti-embolism stockings (AES) Intermittent pneumatic compression Foot impulse devices Subcutaneous low molecular weight heparin (LMWH) Direct oral anticoagulants

Answer 125

As groups of foam cells in the dermis and tendons.

Answer 126

shear force and turbulence surveillance and attack from immune cells (NK Cells) lack of substratum, entrapment in capillary bed

Answer 127

* Cardiac mural thrombi especially in association with a myocardial infarction or atrial fibrillation * Thromboemboli arising in arteries over atheromatous plaques within carotid arteries, the aortic arch or vertebral arteries * Calcific material or vegetations from heart valves * Fragments of atrial myxoma * The venous system if there is a patent foreman ovale

Answer 128

Typically well defined, rounded pushing outer edge, with capsule or pseudocapsule Expansile growth, local effects on the organ or adjacent tissues may be significant Microscopically cells resemble the tissue of origin closely

Answer 129

* **HISTAMINE** – Mast cells, basophils + platelets * **Serotonin** (5-HT) – Platelets * **Vasoactive amines** Immediate early response Response to many injurious stimuli e.g.physical damage immunologic reactions, C3a, C5a, IL-1, factors from neutrophils and platelets Cause vascular dilatation, ↑ venular permeability (endothelial cell contraction) + pain

Answer 130

Pyknosis → karyorrhexis → karyolysis

Answer 131

**What process has occurred?** Haemorrhagic (red) infarction. **Why is the intestine this** **colour** **?** Because numerous vascular anastomoses are present within the small bowel. Occlusion of the main blood supply causes an infarct. The collateral arterial supply is insufficient to rescue the tissue but does allow blood to enter the dead tissue creating a red infarct. **Explain why might this have happened?** Due to loss of blood supply which can be caused by: * Embolism from an atrial or ventricular mural thrombus * Thrombosis of a mesenteric artery secondary to atherosclerosis * Intestinal adhesions wrapped around the bowel occluding the blood supply * Volvulus with resulting occlusion of blood supply

Answer 132

TB in vertebrae.

Answer 133

Melanoma – malignant tumour of cells derived from neural crest

Answer 134

Movement of fluid across vessel wall governed by a balance of forces hydrostatic and colloid osmotic pressure between intravascular and extravascular space.

Answer 135

- naturally occurring anticoagulant - potentiates effect of antithrombin III - mixture of glycosaminoglycan chains extracted from porcine mucosa - antidote = protamine sulphate

Answer 136

**Consists of:** Developing capillaries Fibroblasts and myofibroblasts Chronic inflammatory cells

Answer 137

Constricts to limit blood loss (mechanism not fully understood) Secretes von Willebrand factor which initiates platelet plug formation

Answer 138

**Vasoactive amines**, e.g. histamine, serotonin **Vasoactive peptides**, e.g. bradykinin **Chemokines** (large family of chemotactic proteins) and cytokines (messengers) e.g. IL-1, TNF. Made by WBCs, particularly macrophages. **Arachidonic acid metabolites** from plasma membrane phospholipids e.g. prostaglandins and leukotrienes e.g. LTB4. Anti-inflammatory drugs (e.g. aspirin, NSAIDS, corticosteroids) work by inhibiting their synthesis. • **Nitric** **oxide**

Answer 139

Massive activation of inflammation, widespread vasodilatation, loss of fluid from the vascular spaces into the extracellular space

Answer 140

Scurvy Ehlers-Danlos syndrome Osteogenesis imperfecta Alport syndrome

Answer 141

**_1. Chronic endothelial injury_** * Raised low density lipoprotein (LDL) * Hypertension * Haemodynamic stress * ‘Toxins’ e.g., cigarette smoke **_2. Endothelial dysfunction_** * Platelet adhesion and release of platelet derived growth factor (PDGF) * Monocyte accumulation within intima with release of growth factors and cytokines * T lymphocytes attracted to area **_3. Smooth muscle emigration from media into_** **_intima_** **_4. Macrophages and smooth muscle cells engulf_** **_accumulated,_ _oxidised_** **_lipid and form foam cells_** **_5. Smooth muscle proliferation in response to cytokines and growth factors, collagen and matrix deposition,**_ _**neovascularistaion_**

Answer 142

This is disseminated tuberculosis, wide spread dissemination of tuberculosis throughout the human body resulting in tiny lesions (1–5 mm) which are especially seen on chest x-ray where they appear as tiny spots distributed throughout the lung fields. They resemble millet seeds hence ‘miliary’ tuberculosis. Miliary TB may infect any number of organs, including the lungs, liver, and spleen.

Answer 143

There are six types of necrosis: Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat necrosis Fibroid necrosis Gangrenous necrosis

Answer 144

Schwann cells

Answer 145

Incised, closed, non-infected and sutured wounds Disruption of basement membrane continuity but death of only a small number of epithelial and connective tissue cells Minimal clot and granulation tissue

Answer 146

Inactive enzymatic proteins (e.g. C3a, C5a) made in liver, present in blood Activated by variety of mechanisms: proteolytic enzymes from necrotic cells, anitgen-antibody complexes in infection, gram -ve bacterial (classic and alternate pathways, respectively) and by products of kinin and fibrinolytic systems. The complement cascade generates: * C3b that functions as an opsonin * C5a that attracts neutrophils. * C5-9 complex ("membrane attack complex”) that attaches to the cell causing lysis by cell membrane perforation.

Answer 147

**Coagulative** **necrosis** is characterized by the formation of a gelatinous (gel-like) substance in dead tissues in which the architecture of the tissue is maintained, and can be observed by light microscopy. Coagulation occurs as a result of protein denaturation, causing albumin to transform into a firm and opaque state. This pattern of necrosis is typically seen in hypoxic (low-oxygen) environments, such as infarction. Coagulative necrosis occurs primarily in tissues such as the kidney, heart and adrenal glands. Severe ischemia most commonly causes necrosis of this form. **Liquefactive** **necrosis** (or colliquative necrosis), in contrast to coagulative necrosis, is characterized by the digestion of dead cells to form a viscous liquid mass. This is typical of bacterial, or sometimes fungal, infections because of their ability to stimulate an inflammatory response. The necrotic liquid mass is frequently creamy yellow due to the presence of dead leukocytes and is commonly known as pus. Hypoxic infarcts in the brain presents as this type of necrosis, because the brain contains little connective tissue but high amounts of digestive enzymes and lipids, and cells therefore can be readily digested by their own enzymes. **Gangrenous** **necrosis** can be considered a type of coagulative necrosis that resembles mummified tissue. It is characteristic of ischemia of lower limb and the gastrointestinal tracts. If superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene) **Caseous necrosis** can be considered a combination of coagulative and liquefactive necrosis, typically caused by mycobacteria (e.g. tuberculosis), fungi and some foreign substances. The necrotic tissue appears as white and friable, like clumped cheese. Dead cells disintegrate but are not completely digested, leaving granular particles. Microscopic examination shows amorphous granular debris enclosed within a distinctive inflammatory border. Granuloma has this characteristic. **Fat necrosis** is specialized necrosis of fat tissue, resulting from the action of activated lipases on fatty tissues such as the pancreas. In the pancreas it leads to acute pancreatitis, a condition where the pancreatic enzymes leak out into the peritoneal cavity, and liquefy the membrane by splitting the triglyceride esters into fatty acids through fat saponification. Calcium, magnesium or sodium may bind to these lesions to produce a chalky-white substance. The calcium deposits are microscopically distinctive and may be large enough to be visible on radiographic examinations.To the naked eye, calcium deposits appear as gritty white flecks. **Fibrinoid necrosis** is a special form of necrosis usually caused by immune-mediated vascular damage. It is marked by complexes of antigen and antibodies, sometimes referred to as "immune complexes" deposited within arterial walls together with fibrin.

Answer 148

Faecal occult blood (FOB) test kits are sent to the person’s home. After completing the test the person sends the kit to a laboratory for analysis.

Answer 149

Genetic deficiency in one of components of NADPH oxidase responsible for generating superoxide. Engulfment of bacteria does not result in activation of oxygen-dependent killing mechanisms. X-linked or autosomal recessive. Chronic suppurative granulomas (collections of macrophages surrounded by mononuclear cells) or abscesses affecting the skin, lymph nodes, sometimes lung and liver and osteomyelitis. Neutrophils and macrophages affected.

Answer 150

Tumor depth (T), as described by Breslow's thickness (expressed in millimeters)

Answer 151

Extremely rare autosomal dominant inherited deficiency of C1-esterase inhibitor (component of compliment system) – there is decreased function or decreased levels of the enzyme. Patient experiences attacks of non-itchy cutaneous angio-oedema (rapid oedema of dermis, subcutaneous tissue, mucosa and submucosal tissues) (no urticaria/hives), may last up to 72 hours.

Answer 152

1. **Vitamin K** to overcome the vitamin K antagonism and allow synthesis of vitamin K dependent clotting factors 2. **Prothrombin complex concentrate** (PCC – a mix of factors II, VII, IX and X) if immediate reversal needed

Answer 153

Raised serum amylase in first 24 hours. Raised serum lipase from 72-96 hours. In 10% see glycosuria. Hypocalcaemia possible – due to precipitation of calcium salts in fat necrosis

Answer 154

Hypoxia impairs oxidative phosphorylation resulting in decreased ATP. Low ATP disrupts key cellular functions including the Na+/K+ pump, resulting in sodium and water buildup in the cell. The excess water due to excess sodium is what causes the cell to swell

Answer 155

1. Transient vasoconstriction of arterioles 2. Followed by vasodilatation of arterioles and then capillaries -\> ↑ blood flow 3. ↑ vascular permeability -\> exudation of protein-rich fluid into tissues and slowing of circulation 4. Vascular stasis (because blood is more viscous due to increased concentration of red cells in vessels from leaked fluid)

Answer 156

A calcified tuberculous granuloma in the lung together with granulomas in a hilar lymph node.

Answer 157

**Endothelial cell contraction** -Chemical mediators e.g. histamine, C5a, NO **Endothelial cell injury** - Direct e.g. trauma, chemicals, microbial toxins - Indirect e.g. toxic oxygen species and proteolytic enzymes from neutrophils **Structural** **re-organisation** **of cytoskeleton** -Cytokine mediated e.g. interleukin-1, TNF **Transcytosis** -VEGF induces ↑ channels in endothelial cells

Answer 158

Purulent e.g. meningitis Haemorrhagic/serosanguinous eg malignancies Serous eg: blister Fibrinous: eg: fibrinous pericarditis

Answer 159

1. RUBOR (redness) 2. TUMOR (swelling) 3. CALOR (heat) 4. DOLOR (pain) 5. FUNCTIO LAESA (loss of function)

Answer 160

Eosinophil. The malignant cells (Reed Sternberg cells) release factors that attract them.

Answer 161

Discontinuous distribution Affects any part of the gastrointestinal system ‘Cobblestone’ appearance to bowel mucosa classically seen Granulomas often present Anal lesions common Bowel fistulae likely

Answer 162

Phagocytosis and destruction of debris & bacteria Processing and presentation of antigen to immune system Synthesis of cytokines.- IL, TNF Control of other cells by releasing: EGF, FGF, PDGF (fibrosis and angiogenesis)

Answer 163

WHITE INFARCT: * caused by arterial insufficiency * not reperfused * single blood supply RED INFARCT: * caused by venous insufficiency * reperfused * dual blood supply

Answer 164

Organised collection of epithelioid cells.

Answer 165

1. difficulties in determining dose – this has to be done empirically in each patient with frequent monitoring the INR (measure of prothrombin time). 2. narrow therapeutic window 3. drug/diet interactions 4. delay in efficacy as pre-existing factors is still available for use.

Answer 166

A genetically inherited disorder. The liver produces a version of the protein α1- antitrypsin that is incorrectly folded. This cannot be packaged by the endoplasmic reticulum and accumulates within this organelle and is not secreted by the liver. The systemic deficiency of the enzyme means that proteases within the lung can act unchecked and patients with the condition develop emphysema as lung tissue is broken down.

Answer 167

The irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.

Answer 168

Bacillus Calmette-Guérin This is a vaccine against tuberculosis that is prepared from a strain of the attenuated (virulence-reduced) live bovine tuberculosis bacillus, Mycobacterium bovis that has lost its virulence in humans.

Answer 169

**Lysis** - complete dissolution of thrombus **Propagation** - progressive spread of thrombosis **Organisation** - growth of fibroblasts and capillary proliferation (similar to granulation tissue), which result in the attachment of the thrombus to the vessel wall **Recanalisation** - one or more channels formed through organising thrombus, bloodflow re-established but usually incompletely **Embolism** - part of thrombus breaks off travels through bloodstream lodging at distant site

Answer 170

* Mitogenic for epithelial cells, hepatocytes and fibroblasts * Produced by keratinocytes, macrophages and inflammatory cells * Binds to epidermal growth factor receptor (EGFR)

Answer 171

1. EXUDATE of [oedema] FLUID 2. INFILTRATE of [inflammatory] CELLS

Answer 172

Embolism of atheroma or thrombus to the legs causing acute ischaemia . Aortic dissection causing acute aortic occlusion or aortic rupture. Aorto-caval or aorto -duodenal fistulae.

Answer 173

Virchow's triad describes the three broad categories of factors that are thought to contribute to thrombosis. Hypercoagulability Hemodynamic changes (stasis, turbulence) Endothelial injury/dysfunction

Answer 174

Ulcer = breach in mucosa to level of submucosa or deeper.

Answer 175

Extent of tumour at the primary site (**T status**). Regional metastasis (Lymph nodes-**N status**) Distant metastasis (**M status**)

Answer 176

A rapid onset of cerebral deficit (usually focal) lasting more than 24 hours or leading to death, with no cause apparent other than a vascular one.

Answer 177

* **Transudate** = low protein content e.g. heart failure (increased hydrostatic pressure but vessel intact and don’t leak plasma proteins so colloid osmotic pressure static) * **Exudate** = high protein content, e.g. acute inflammation

Answer 178

Hypertension

Answer 179

**Ziehl-Neelsen stain** – stains mycobacteria. **Polymerase chain reaction** – a process that can be used to identify small amounts of DNA. In this case mycobacterial DNA. **Culture** **of the tissue** – in an attempt to grow mycobacteria.

Answer 180

* Modulate the inflammatory response * Short-lived * Endogenous (derived from plasma proteins, leucocytes and local tissues) or exogenous (e.g. endotoxin from gram negative bacteria) * Every mediator has an inhibitor

Answer 181

**Unipotent** Most adult stem cells Only produce one type of differentiated cell, e.g. epithelia **Multipotent** Produce several types of differentiated cell, e.g. haematopoietic stem cells **Totipotent** Embryonic stem cells Can produce any type of cell and therefore any tissues of the body

Answer 182

1. pale 2. granular 3. lines of Zahn 4. lower cell content

Answer 183

* MTB enters macrophages by endocytosis * MTB replicates within phagosome. It can do this as it blocks the fusion of phagosome and lysosome. It then proliferates in pulmonary alveolar macrophages and airspaces. Bacteraemia develops and there is seeding of multiple sites (the illness at this stage is asymptomatic or gives symptoms of a mild flu-like illness) * Approximately 3 weeks after infection T helper cell response against MTB is mounted that activates macrophages to become bactericidal (T helper cells produce IFNγ) * Activated macrophages produce TNF (tumour necrosis factor), this recruits monocytes which differentiate into ‘epithelioid histiocytes’ forming granulomas. In many this contains the illness. * In some infection progresses. The immune response results in tissue destruction due to caseation and cavitation.

Answer 184

* α-fetoprotein (AFP) – non-seminomatous germ cell tumours especially yolk sac tumour. * Human chorionic gonadotropin (HCG) – non-seminomatous germ cell tumours; marked elevation if choriocarcinomatous elements are present; approximately 15% of seminomas have syncytiotrophoblastic giant cells and a minimal increase in HCG levels.

Answer 185

Ulceration due to imbalance of acid and pepsin attack and mucosal defence. Sites- antrum, first part of duodenum Causes- Helicobacter pylori (HP gastritis), hyperacidity Drugs-NSAID, genetic

Answer 186

Fatty streak Simple plaque Complicated plaque

Mechanisms of disease Flashcards

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