review 2 PP

Question 1

Which of the following substances are released by and activate platelets?

Answer 1

Both ADP and thromboxane A2

are released by activated platelets and cause further platelet activation. Histamine and serotonin are also released by platelets but they don’t activate platelets. ADP activates P2Y12 (GPCR) receptors on the platelet membrane to initiate signalling cascades that promote aggregation. P2Y12 is the target of the antithrombotic drug clopidogrel.

Question 2

Which of the following are two of the 12 clotting factors but are now identified by name rather than Roman numerals?

Answer 2

Calcium is factor IV and thromboplastin (or tissue factor) is factor III.

Question 3

A 64 year old with a known malignancy is found to have hypercalcaemia. A blood test reveals a high level of parathyroid hormone related protein.

Which neoplasm is this patient most likely to have?

Answer 3

Bronchial squamous cell carcinoma can produce parathyroid hormone related peptide.

Question 4

A 71 year old woman has a TIA. She had a myocardial infarction five years ago.

Which of the following physical examination findings is most likely to be related to her TIA?

Answer 4

Carotid bruit

Question 5

A 48 year old man is invited to see his GP for a health check. The man has a 30 pack-year history of smoking, a BMI of 42 and his blood pressure is 181/111 mmHg. The GP considers the man to be at risk of developing atherosclerosis.

What is a direct complication of this condition?

Answer 5

stroke

Question 6

A four year old boy is seen by a paediatrician as his parents are concerned about his vision. He is found to have a malignancy of the left eye. This is treated with radiotherapy. Two years later he develops a similar malignancy in the right eye.

What is the normal function of the protein that is altered in this condition?

Answer 6

This child’s history indicates that he has had bilateral retinoblastoma. In this condition there is mutation of the RB gene. The normal function of the RB protein is to inhibit cell cycle progression and hence it inhibits cell proliferation.

Question 7

The Ann Arbor classification system is used to stage a specific type of cancer. It is named after the city Ann Arbor, Michigan USA, where a committee met in 1971 to agree on the criteria.

Which type of cancer is staged by this system?

Answer 7

lymphoma

Question 8

A 56 year old man presents to his GP for a routine health check. The man has a BMI of 42, he is a smoker and has a blood pressure of 163/102 mmHg. The GP tells the man that he is at risk of developing atherosclerosis.

In which region of the artery wall does this condition first start to develop?

Answer 8

tunica intima

Question 9

A 62 year old woman has a myocardial infarction. A month later she has symptoms of left ventricular failure and an echocardiogram is performed. This demonstrates an area of non-functioning myocardium in the left anterior ventricular wall with an overlying thrombus.

Which site is this thrombus LEAST likely to embolise to?

Answer 9

lungs

Question 10

A 16 month old boy is referred to the ophthalmology unit for evaluation of bilateral leukocoria (white pupils), acute glaucoma and nonreactive pupils. Subsequent testing reveals that the boy has retinoblastoma, a disease resulting from mutation of the retinoblastoma gene.

Retinoblastoma

What is the role of the protein encoded by this gene?

Answer 10

Inhibits cell cycle progression until a cell is ready to divide

Question 11

A cell biologist is investigating the effects of a new anti-cancer drug on the cell cycle

At which point in this cycle are the chromosomes replicated?

Answer 11

S phase

Question 12

A 78 year old woman with a 10 year history of heart failure presents to A&E with dyspnoea, tachycardia, haemoptysis and pleuritic chest pain. She has a BMI of 31, her blood cholesterol is 6 mmol/L and she suffers from stage 3 hypertension. She also has a damaged aortic valve resulting from infective endocarditis 6 years previously. The woman is currently suffering from a pulmonary embolism that originated from a deep vein thrombus in her left femoral vein.

What factor in this patient’s history specifically increases her risk of venous thromboembolism?

Answer 12

CORRECT – Venous thromboembolism (VTE) is primarily driven by stasis and hypercoagulability and arterial thromboembolism is driven by endothelial damage and hypercoagulability. The woman’s obesity can lead to a hypercoagulative state. This is because the increased adipose tissue in obese patients can increase the aromatisation of endogenous androgens (e.g testosterone) into oestrogen. This increased oestrogen can increase clotting factor synthesis in the liver. However, hypercoagulability is not specific to VTE, instead it is the woman’s heart failure that increases her risk of VTE. The Heart failure decreases the cardiac output of the heart and leads to decreased venous return. This allows blood to accumulate in capacitance vessels in the venous system leading to stasis. Stasis is a critical factor in increasing a patient’s risk of VTE.

Question 13

An 18 year old woman undergoes genetic testing following diagnosis of her older sister with alpha-1 antitrypsin deficiency.

Which of the following conditions are classically seen in this disease?

Answer 13

Emphysema and cirrhosis

Alpha-1 antitrypsin deficiency is an autosomal recessive disorder in which there are low levels of alpha-1 antitrypsin, a protease inhibitor which deactivates enzymes released from neutrophils at the site of inflammation. Patients develop emphysema as proteases released by neutrophils within the lung act unchecked and destroy normal parenchymal tissue. The hepatocytes produce an abnormally folded version of the alpha-1 antitrypsin protein which polymerises and cannot be exported from the endoplasmic reticulum. This causes hepatocyte damage and eventually cirrhosis. Cutaneous angio-oedema and recurrent abdominal pain are features of hereditary angio-oedema. Recurrent infections and skin abscesses are features of chronic granulomatous disease. Haemoptysis and chest pain raise the possibility of tuberculosis or lung cancer. Arthralgia and enlarged lymph nodes are seen in sarcoidosis.

Question 14

A 72 year old man develops sudden onset abdominal pain and collapses. On admission to hospital he is found to have a leaking abdominal aortic aneurysm. He is taken to theatre and the aneurysm is repaired. In theatre he is transfused 10 units of blood. Four hours after the operation he is found to have a platelet count of 25 x 109/L.

What is the most likely explanation for his thrombocytopenia?

Answer 14

blood transfusion

Question 15

A 67 year old man presents with breathlessness on exertion and palpitations. On examination he is found to have a mid-systolic murmur heard best over the apex of the heart. Mitral valve stenosis is suspected and this is confirmed by echocardiography.

Which of the following is most likely to be seen in this condition?

Answer 15

left atrial hypertrophy

Question 16

A 57 year old man has a history of ischaemic heart disease secondary to coronary artery atherosclerosis.

Which of the following conditions can also occur secondary to atherosclerosis?

Answer 16

Colitis
Atherosclerosis can cause ischaemic colitis when arteries supplying the colon are narrowed or blocked by atherosclerotic plaques. Similar obstruction to the vessels can also occur secondary to embolism of plaque material or thrombus that has formed on a plaque more proximally in the arterial supply. Cirrhosis (a chronic liver disease with hepatocyte damage followed by fibrous scarring with nodular regeneration of hepatocytes) can be caused by, amongst a few other rarer conditions, excess consumption of alcohol, steatohepatitis (fatty liver), chronic hepatitis C or hepatitis B infection, reaction to drugs or toxins, autoimmune diseases and a number of hereditary conditions such as alpha 1-antitrypsin deficiency. Causes of nephritis (inflammation of the kidney) include autoimmune disorders, infections and toxins. Causes of pancreatitis can be remembered using the mnemonic ‘I GET SMASHED’ = Idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps/Malignancy, Autoimmune, Scorpion sting, Hypercalcaemia/Hypertriglyceridaemia, ERCP, Drugs. Thrombophlebitis is inflammation of a vein related to a blood clot. It occurs in people who have an increased risk of blood clotting, i.e., the triad of Virchow (endothelial damage, slow or turbulent blood flow, hypercoaguability).

Question 17

types of cartilage

Answer 17

Question 18

A 73 year old man presents with confusion and vomiting. Blood tests reveal a serum sodium concentration of 126 mmol/L (ref: 135-145) and a serum osmolality of 262 mOsm/kg (ref: 285-295). Other blood tests are normal.

Which of the following lung tumours is the patient most likely to have?

Answer 18

Small cell carcinoma
The patient has a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Of the lung tumours listed, small cell carcinoma is most likely to produce ADH. If lung squamous cell carcinomas produce an ectopic hormone it is usually parathyroid hormone related protein. Adenocarcinomas of the lung do not tend to produce ectopic hormones. Well-differentiated neuroendocrine carcinomas of the lung produce hormones less frequently than do well-differentiated neuroendocrine tumours of the GI tract. When they do so the hormones tend to be vasoactive amines such as serotonin and/or histamine. A hamartoma is a mass of disorganised but mature specialised tissue indigenous to the lung resulting from aberrant differentiation. It does not liberate hormones.

Question 19

A cell biologist is investigating a potential anti-cancer drug which works by restricting the cell’s ability to replicate DNA by preventing progression from the G1 (first gap phase) to S (synthesis phase) phase of the cell division cycle.

Which endogenous protein normally plays this role in the cell cycle?

Answer 19

Retinoblastoma (Rb)
CORRECT – The retinoblastoma protein is a tumour suppressor protein that is crucial for the regulation of the restriction point. The protein must be phosphorylated in order to allow for the progression of a cell through the checkpoint. It is phosphorylated by cyclin dependent kinases (e.g CDK2 and CDK4) which are activated by binding to cyclin proteins (e.g Cyclin D). The production of cyclins is activated by the stimulation of proteins that are coded for by proto-oncogenes like the RAS G-Protein. Another protein that inhibits progression through this checkpoint is the P53 protein.

Question 20

Which of the following is a granulocyte?

Answer 20

A granulocyte is a white blood cell with secretory granules within it’s cytoplasm. Neutrophils, eosinophils, basophils and mast cells are granulocytes. The granules contain enzymes that damage or digest pathogens. Platelets also contain granules and some would also classify them as granulocytes.

Question 21

A 48 year old man with type IIa familial hyperlipidaemia dies from a myocardial infarction after experiencing a central, crushing chest pain. A histological sample taken from his right coronary artery during post-mortem is processed for wax embedding before a section is stained and viewed under the microscope. The histopathologist viewing the section notes the presence of cholesterol clefts within an atherosclerotic plaque in the artery wall.

What is responsible for the formation of this type of cleft within an atherosclerotic plaque?

Answer 21

Tissue processing for microscopy
CORRECT – As a plaque grows, the cells in the centre of the plaque die and necrosis develops. The dead cells release cholesterol and cholesterol crystals appear in the plaque. The crystals are removed during tissue processing for microscopy leaving behind linear holes in the tissue section. These holes are cholesterol clefts.

Question 22

collagen

Answer 22

Question 23

A 22 year old man works in a textiles factory Bangladesh where his job is to make aniline purple dye. As part of this work, he is regularly exposed to the carcinogen, 2-napthylamine.

What specific cancer is the man at risk of developing due to this exposure?

Answer 23

transitional cell carcinoma of the bladder

Question 24

A 78 year old woman is diagnosed with breast cancer.

What marker would be most appropriate to monitor progression of her cancer and the effectiveness of any treatment?

Answer 24

CA 15-3

Question 25

Which of the following is a co-factor required for effective clotting?

Answer 25

calcium

Question 26

what is not found in haemophilia

Answer 26

PT is not raised as there is no defect in the extrinsic pathway.

Question 27

A 5 month old girl is referred to the Haematology department for evaluation of bleeding from her gums and the appearance of subcutaneous discolorations that look like bruising but are not related to any physical injury (ecchymosis). Her medical notes showed that she had been diagnosed with a urinary tract infection 2 weeks ago and that she is currently receiving ceftriaxone (a cephalosporin) treatment for this. Coagulation tests showed a prothrombin time (PT) of 60s (10–14 and an activated partial thromboplastin time (aPTT) of 144 s (20–36). Platelet count and platelet function tests were normal.

What is the most likely cause for this girl developing bleeding and ecchymosis?

Answer 27

CORRECT – Treatment with MTT side chain containing cephalosporins can result in a clinically relevant coagulopathy due to a deficiency in active vitamin K dependent clotting factors.

Question 28

A 56 year old woman is referred to the Oncology department after developing a lump in the upper outer quadrant of her left breast. Mammography revealed a 1.8 cm tumor which on biopsy was shown to be a HER2-positive infiltrating ductal grade 3 carcinoma. HER2 gene mutations are implicated in up to 25% of breast cancers.

Mutation of this gene enables which of the 6 hallmarks of cancer?

Answer 28

self sufficiency in growth signal

Question 29

A 57 year old man has a history of ischaemic heart disease secondary to coronary artery atherosclerosis.

Which other condition can occur as a direct result of atherosclerosis?

Answer 29

impotence

Question 30

A 58 year old man presents to the accident and emergency department with jaundice and abdominal tenderness. He also complains that he has been feeling wheezy and short of breath over the past year. Blood tests reveal that his α1-antitrypsin levels are below the normal range and subsequent genetic testing reveals that he has an inherited form of α1-antitrypsin deficiency.

Accumulation of which substance in this patient’s hepatocytes has led to his jaundice and abdominal tenderness?

Answer 30

Protein
CORRECT – α1-antitrypsin deficiency is an autosomal recessive disorder with varying levels of severity in which there are low levels of α1-Antitrypsin, a protease inhibitor which deactivates enzymes released from neutrophils at the site of inflammation. Patients with the disorder develop emphysema as neutrophil elastase released by neutrophils within the lung acts unchecked and destroys parenchymal tissue (α1-antitrypsin normally inhibits neutrophil elastase). Liver disease also occurs as the hepatocytes produce an abnormal version of α1-antitrypsin, which is incorrectly folded. This abnormal α1-antitrypsin polymerises and cannot be exported from the endoplasmic reticulum, meaning that it accumulates inside the liver cells. This causes hepatocyte damage and eventually cirrhosis.

Question 31

A 22 year old man fractures his tibia after falling off a Quad bike. A cast is applied in A&E and the man is sent home. Two days later he suffers an ischaemic stroke of his right middle cerebral artery. The man is not a smoker and his medical notes show no major medical diagnoses of note. He has a BMI of 21 and an LDL level of 2.2mmol/L.

What is the most likely cause of this man’s stroke?

Answer 31

Fat embolus passing from the broken leg to the cerebral vasculature
CORRECT – When a bone is fractured the bone marrow fat cells that are injured break up and release oil droplets. These coalesce over a period of a few days and are then sucked into gaping venules that have been torn by the fracture. Symptoms of fat embolism (respiratory distress and neurological symptoms) are therefore seen one to three days after the fracture. They are said to occur in 5-10% of patients with pelvic or long bone fractures and mortality is 10-15%. Respiratory symptoms are the result of emboli that lodge in the lungs. Some droplets however will pass through the lungs in a similar way to small thromboemboli and into organs such as the brain, kidneys and skin where they will cause symptoms such as a stroke.

Question 32

Ischaemia of an organ can result in either coagulative or liquefactive necrosis.

In which of the following organs is liquefactive necrosis most likely to be seen following ischaemia?

Answer 32

Brain
Liquefactive necrosis is classically seen either when large numbers of neutrophils are present (releasing proteases) or in soft organs without a collagenous framework. It is therefore seen in the brain with ischaemia. Coagulative necrosis is seen after ischaemia in the other organs listed.

Question 33

The attached picture is of the heart of a 72 year old man who died suddenly at home.

Which of the following is most likely to cause this appearance?

Answer 33

Mitral valve regurgitation
The picture shows left ventricular hypertrophy. The commonest causes of left ventricular hypertrophy are systemic hypertension, ischaemic heart disease, aortic stenosis, aortic regurgitation, mitral regurgitation (the correct answer to the question), hypertrophic cardiomyopathy and exercise. In mitral regurgitation the mitral valve is incompetent and during systole, as well as blood being ejected through the aortic valve, some will pass back into the left atrium through the incompetent mitral valve. The left ventricle will therefore have to work harder to maintain the systemic blood pressure and left ventricular hypertrophy is the result. Mitral valve stenosis leads initially to left atrial hypertrophy. Pulmonary hypertension and pulmonary valve stenosis cause right ventricular hypertrophy. Tricuspid valve stenosis causes right atrial hypertrophy.

Question 34

A 76 year old woman collapses suddenly and dies. A post mortem is performed and the cause of death is found to be a haemorrhagic stroke. The cerebral arteries are seen to show significant atherosclerosis.

Which other disease is most likely to be contributory to the cause of death?

Answer 34

Hypertension
Hypertension is a major risk factor for haemorrhagic stroke. It is particularly dangerous when cerebral blood vessel walls are weak, as for example in atherosclerosis. Atrial fibrillation is frequently associated with strokes but these are usually as a result of embolisation of thrombus that forms due to blood turbulence in the fibrillating atrium. Alzheimer’s disease, colonic cancer and left ventricular failure are not risk factors for haemorrhagic stroke.

Question 35

Speed of onset is important in acute inflammation.

Which of these chemical mediators is available immediately at the site of injury in an active form?

Answer 35

Histamine
Histamine is stored pre-formed in the granules of mast cells, basophils and platelets. Bradykinin is formed from circulating kininogen by the action of the enzyme kallikrein. C5a is produced when the membrane attack complex is formed from circulating proteins. FDPs are breakdown products of fibrinogen. Phospolipase acts on membrane phospholipids to produce arachadonic acid. Within white cells, this is metabolised by lipoxygenase to produce leukotrienes.

Question 36

A 74 year old man presents with a persistent cough and night sweats. On examination he is found to have an enlarged lymph node in his neck. A biopsy is taken and the histology report describes the presence of granulomas.

What needs to be observed in order to allow for a histological diagnosis of this type of chronic inflammation?

Answer 36

Epitheloid histiocytes
CORRECT – Epitheloid histiocytes are macrophages that have become modified to look like epithelial cells in that they are elongated, have eosinophilic cytoplasm and appear tightly packed together as epithelial cells do. They only present in granulomatous inflammation.

Question 37

A 67 year old man is prescribed aspirin after a transient ischaemic attack (TIA).

Which of the following is true regarding this drug?

Answer 37

It leads to a reduction in the syntghesis of thromboxane A2
Aspirin irreversibly inhibits cyclooxygenase-1. This enzyme produces thromboxanes from arachidonic acid. Thromboxane A2 activates platelets, therefore aspirin will reduce platelet agggregation and has an anti-coagulant effect. Steroids inhibit phospholipase. Warfain inhibits vitamin K.

Question 38

A 27 year old man is referred to the Haematology Department for evaluation of recurrent venous thromboses. Further testing reveals that the man has Factor V Leiden, a mutated form of factor V. Factor V is involved in the clotting cascade and is normally inhibited by an anticoagulant in blood which prevents the pro-clotting activity of factor V. This inhibition is lost in Factor V Leiden because the mutated protein it is no longer cleaved and degraded by the anticoagulant and this leads to a hypercoagulable state.

What is this anticoagulant?

Answer 38

Protein C
CORRECT – Thrombin can act as to inhibit its own production via a negative feedback loop. This gives greater endogenous control over the clotting cascade. A primary mechanism by which thrombin regulates its own production is via the production of Protein C. Thrombin is able to bind to Thrombomodulin, expressed on the surface of endothelial cells. This binding stimulates the production of Protein C, a protease which (using Protein S as a cofactor) is used to inactivate Factors Va and VIIIa. Factor V Leiden is an autosomal dominant disorder in which the Factor V protein is structurally changed in a way that means that Protein C is unable to efficiently inactivate it.
Protein_C

Question 39

A 64 year old man presents with difficulty swallowing and feeling that food is sticking in his chest. He has lost 8kg over the last month. An upper gastrointestinal endoscopy is performed and a tumour is seen in the patient’s mid oesophagus. This is biopsed. The picture is of the histology of the tumour.

What type of cancer is this?

Answer 39

Squamous cell carcinoma
All of these tumours can occur in the oesophagus although adenocarcinoma and squamous cell carcinoma are the commonest of the five. They have a roughly similar incidence, although the the incidence of adenocarcinoma is rising in Europe and the US. The cancer in the picture consists of nests of pale pink cells which show keratinisation in the centre of the nests. No glandular structures are present. This cancer is therefore a squamous cell carcinoma.

Question 40

what is this

Answer 40

artery thrombi
lines of zahn

Question 41

A 58 year old man with a history of chronic alcohol abuse and an IV drug use is admitted to A&E with severe confusion. Upon assessment it was determined that he had 6 necrotic toes and his fingers were turning purple. He also had haematuria, petechiae on his arms and legs and blood tinged secretions from his mouth and nose. Coagulation tests reveal a raised APTT, PT and bleeding time. Blood tests reveal raised D-Dimers, thrombocytopenia and haemoglobin below the normal range.

What condition most likely explains this man’s haematological abnormalities?

Answer 41

Disseminated Intravascular Coagulation
CORRECT – Disseminated intravascular coagulation (DIC) is a thrombohaemorrhagic disorder occurring as a secondary complication in a variety of conditions. In DIC clotting cascade is activated and microthrombi form throughout the circulation. This process consumes platelets, fibrin and coagulation factors and activates fibrinolysis. The patient may then experience haemorrhage due to the decreased clotting factors. The microvascular thrombosis results in conditions such as neurological impairment, gangrene of the skin, renal failure, respiratory distress and gastrointestinal ulceration. The haemorrhagic component results in conditions such as intracerebral bleeding, petechiae, haematuria, epistaxis and gastrointestinal bleeding. As the fibrinolytic system is activated FDPs such as D-dimer are released in large numbers and can be measured in the blood. Red blood cells are often traumatised and fragmented as they squeeze past the microthrombi, resulting in anaemia (microangiopathic haemolytic anaemia). DIC never occurs as a disease in itself but is always a complication of another condition, e.g., sepsis (especially gram negative sepsis as such bacteria produce endotoxin which activates clotting), severe trauma (especially to the brain as it contains large amounts of thromboplastin), extensive burns, complications of childbirth (e.g., amniotic fluid embolism, retained dead foetus), malignancy, snake bite, IV drug use.

Question 42

A 62 year old man with ischaemia of his right leg has a femoral embolectomy. The embolus is sent for histological examination and the histology report describes the presence of cholesterol clefts.

Which other condition is this man most likely to have?

Answer 42

Abdominal aortic aneursym
The correct answer is abdominal aortic aneurysm as the embolus contains cholesterol indicating that it is likely to have come from an atherosclerotic plaque. The majority of abdominal aortic aneurysms occur as the result of atherosclerosis from which atheroma can break off and embolise to the legs. Atrial fibrillation and left ventricular aneurysm can result in cardiac thrombi which can embolise but which do not contain cholesterol crystals. An atrial myxoma is a benign tumour of the heart, parts of which can embolise, but again the emboli wouldn’t contain cholesterol. Endocarditis (inflammation of the endocardium) usually involves the heart valves. It is characterised by vegetations on the valves which can embolise. The vegetations are composed of thrombus and microorganisms and again do not contain cholesterol crystals.

Question 43

A 74 year old man presents with a painful, pale and cold right foot. No pedal pulses can be felt. The signs and symptoms are thought to be due to a thromboembolism.

From where is the thromoboembolus LEAST likely to have arisen?

Answer 43

Femoral vein
This embolus must have lodged within an artery in order to cause ischaemia and must be of a significant size to result in an ischaemic foot. Systemic emboli of this size must arise from the left side of the heart or the arteries (as if they arose in a vein they would lodge in the small vessels of the lung and not make it to the arterial circulation). They can only arise from the veins when there is a connection between the right and left sides of the heart, e.g., patent foreman ovale or ventricular septal defect. Such emboli are rare. They are called paradoxical emboli. So in this case, the least likely origin of the embolus is the femoral vein. All the other options are much more likely.

Question 44

Which of the following molecules requires vitamin K for it’s synthesis?

Answer 44

Prothrombin
The vitamin K dependent clotting factors are II, VII, IX and X. Prothrombin is factor II. The anticoagulents protein C and protein S also require vitamin K for their synthesis.

Question 45

Which of the following substances does NOT circulate within the blood?

Answer 45

Fibrin
Fibrin is an insoluble protein that is formed from the soluble protein fibrinogen. Fibrinogen circulates within the blood but fibrin does not. All the other options circulate within the blood. Von Willebrand factor circulates in the blood bound to factor VIII. It stabilises factor VIII and slows its degradation. Von Willebrand factor is also present within the endothelium and platelets and in the subendothelial connective tissue.

Question 46

In acute inflammation prostaglandins are produced.

Which statement is true?

Answer 46

Prostaglandins are produced from cell membrane phospholipids
Prostaglandins can be produced by most cells. Phospholipase A2 produces arachidonic acid from plasma membrane phospholipids. Arachidonic acid is metabolised by cyclooxygenase to produce prostaglandins. Prostaglandins have an important role in vasodilatation and pain sensation. The membrane attack complex is produced by assembly of circulating polypeptides (the complement components). Bradykinin is produced by cleavage of circulating kininogen by the enzyme kallikrein. Cytokines, e.g., interleukins, interferons and tissue necrosis factor are secreted by macrophages. Histamine and seratonin are stored preformed in cells.