BII

Question 1

What is haematopoiesis?

Answer 1

The process by which mature blood cells are generated from stem cells in the bone marrow

Question 2

Define pancytopenia

Answer 2

Low levels of all categories of blood cell types

Question 3

Where does haematopoiesis occur?

Answer 3

Non lymphoid cell generation is completed 95% in the bone marrow of ribs, long bones, sacrum etc., and 5% in the spleen

Question 4

Describe the development of blood cells

Answer 4

Stem cells generate progenitor cells
Progenitor cells generate morphologically identifiable progeny that progressively mature
As they mature they lose their ability to proliferate and become post-mitotic

Question 5

What are some of the different cells formed by haematopoiesis?

Answer 5

Neutrophils- life of 5-6 hours then move into tissues
T and B lymphocytes
Granulocytes
Macrophages
Erythrocytes- life of 120 days
Megakaryocytes- life of 5-6 days

Question 6

What are stem cell niches?

Answer 6

Endothelial and endosteal types that support the normal activities of stem cells.

Question 7

Where does haematopoietic tissue come from?

Answer 7

Cells of haemopoietic are generated from the mesoderm in blood islands of the yolk sac, to produce transient primitive blood cells, and then definitive cells emerge from the endothelium in the aorta-gonad mesonephros region. The site of haematopoiesis shifts to the fetal liver, and then to bone marrow.
The primitive haemagnioblasts proce haemopoietic and endothelial cells, whereas the endothelium produces only haemopoietic tissue

Question 8

How does our bone marrow change as we age?

Answer 8

In infancy, all bone marrow is haematopoietic, but there is progressive fatty replacement of marrow in the long bones, so that in adult life, haematopoietic tissue is only in the axial skeleton, and approx. 50% of this is replaced by fat. This is important as when diagnosing conditions we should be biopsying active marrow only

Question 9

What can happen to fatty marrow?

Answer 9

It can revert to haematopoietic tissue.

Question 10

Describe extramedullary haematopoiesis

Answer 10

The spleen and liver resume their fetal haematopoietic roles.

Question 11

Describe bone marrow in an adult

Answer 11

Includes trabecular bone, which contains fat and haematooietic tissue. Cellularity varies and decreases with age. Major cellular elements are haematopoietic cells and stromal cells, including fibroblasts, macrophages, fat cells and endothelial cells. They provide support and a microenvironment suitable, consisting of extracellular matrix, adhesion molecules and blood cells growth factors.
On slides, the pinkish stuff is bone, white spaces are fats and purple cells are the haematopoietic cells.

Question 12

What are the properties of haematopoietic stem cells?

Answer 12

Self renewal

Generation of one or more specialised cell types

Question 13

How do we measure HSCs?

Answer 13

They all express the antigen CD34 which can be used as a proxy

Question 14

What is the difference between immature and mature blood cells?

Answer 14

Immature are made in the bone marrow, while mostly only the mature ones are seen in circulation

Question 15

What are the major factors regulating haematopoiesis, and what do they do?

Answer 15

Transcription factors that switch on and off to control cell programming.
Cytokines, which are the most clinically useful. They are growth factors produced by the marrows, for which stem cells have receptors.
Includes EPO- increases RBCs
TPO- increases platelets
G-CSF- Increases neutrophils

Question 16

What are the main ways of assessing blood and bone marrow?

Answer 16

Peripheral blood count- full blood count. Usually automated, giving absolute numbers of cell types. Blood film can be examined to look at morphology
Bone marrow exam- aspirated at look at the liquid marrow, or trephine produces a core biopsy, good for histological exam of architecture. Usually taken from post iliac crest
Stem cells- assessed indirectly by colony assays and CD34 measurement

Question 17

Where can we source stem cells from?

Answer 17

Umbilical cord blood. There is 60-100mL of immunologically naive blood remaining in the cord

Question 18

Describe myelofibrosis

Answer 18

Scarring of marrow tissue, causing few marrow cells and lots of collagenous tissue. Patients develop hepato- and splenomegaly due to reversion to the fetal state, and show extramedullary haemapoiesis. (A similar thing happens in children with untreated thalassemia, but the bone marrow itself also expands).

Question 19

What are the main three properties of red blood cells?

Answer 19

Unique shape and deformability
No nuclei or mitochondria, but still need energy
Carry haemoglobin

Question 20

Why is the red blood cell’s shape and deformability important?

Answer 20

Allows gas exchange and movement through small capillaries
This propety is determined by membrane and cytoskeletal proteins. Inherited abnormalities of this membrane can cause decreased red cell lifespan due to haemolysis. It can cause anaemia if Hb drops.

Question 21

How do red blood cells produce energy?

Answer 21

They have glycolytic pathways, as well as an HMP shunt to produce NADPH and keep Hb reduced. Inherited defects in these pathways lead to increased haemolysis

Question 22

How do red blood cells carry haemoglobin?

Answer 22

In adults it is mainly done by using HbA. This consists of 2 alpha and 2 beta chains with a haem group. There are also small amounts of HbF and HbA2. Defective production of globin chains is qhat causes thalassemia, while irod deficiency causes reduced Haem production and low Hb.

Question 23

How do erythroids develop?

Answer 23

They start as part of the myeloid multilineage progenitor, and respond to growth factors including IL-2 and GM-CSF. They have erythroid burst forming units, and then colony forming units. They then reach the morphological stages, where they differentiate- there is progressive increase of Hb and chromatin, clumping, extrusion of the nucleus and loss of RNA
They take 7-10 days to develop, and so this is how long you must wait to see changes after treatment.
As they spend 2 days as reticulocytes, reticulocytes in the blood can be used to measure erythrocyte production- high in blood loss or haemolysis, or low in bone marrow failure

Question 24

What are the critical requirements of erythropoiesis?

Answer 24

Iron
Folate
B12

Question 25

What regulates erythropoiesis?

Answer 25

Erythropoietin- a glycoprotein produced in the kidney, especially in response to low oxygen

Question 26

What does erythropoietin do?

Answer 26

``` Acts through EPO receptors to stimulate PFU-E and CFU-E Increases haemoglobin synthesis Reduces RBC maturation time Increases reticulocyte release Increases Hb Increase O2 delivery ```

Question 27

What can some side effects of EPO be?

Answer 27

Renal failure patients can get low Hb | Can be used in clinics to treat anaemias, but has potential for abuse

Question 28

How are RBCs broken down?

Answer 28

Cells becomes less deformable and are removed in the spleen Broken down with release of Hb, which is then broken down into globin chains and haem Iron is carried by transferrin back to the bone marrow Protoporhyrin is coverted into bilirubn in the liver, and secreted as bile

Question 29

What is anaemia?

Answer 29

Reduction in Hb concentration in the blood, usually but not always accompanied by a fall in RBC count and packed cell volume Alterations in plasma volume (eg dehydration) can also mask anaemia or cause polycythemia.

Question 30

What are the clinical features of anaemia?

Answer 30

Increased SV and HR Right shift in the haemoglobin dissociation curve (making O2 more available to tissues) Can be asymptomatic, but eventually, patients will develop SOB, fatigue, pallor and congestive cardiac failure. Degree of symptoms depends on speed of onset, severity and age of patient.

Question 31

What are the different categories of anaemia?

Answer 31

Macrocytic | Microcytic

Question 32

What are the most common URTIs in NZ?

Answer 32

Colds, bronchiolitis, pharyngitis and influenza | Distantly followed by pneumonia and tuberculosis

Question 33

What is a URT?

Answer 33

Upper respiratory tract- everything above the level of the alveoli. Includes sinusitis, otitis media, pharyngitis, tracheitis, bronchitis and pneumonia.

Question 34

What are symptoms of a URTI?

Answer 34

The middle ear and sinuses are common sites The mucosa swells as fluids, antibodies etc filter into them. This can cause difficulty breathing through the nose, blockage of eustachian tube and fluid accumulation in the middle ear

Question 35

What are the common causes of respiratory infection?

Answer 35

Strep Pyogenes Strep Pneumoniae Haemophilus influenzae Rhinoviruses Coroaviruses Resp syncytial viruses Influenza virus

Question 36

What is the difference between Strep pyogenes and Strep pneumoniae in terms of presentation?

Answer 36

Pyogenes only causes pharyngitis Pneumoniae causes infection in the middle ear, maxillary and frontal sinus issues, alveolar issues. While it is the most important cause of sinusitis, bronchitis and pneumonia it is not a cause of pharyngitis

Question 37

What is pharyngitis?

Answer 37

Same as tonsilitis or sore throat. Can involve tonsils, soft palate, uvula, and cervical adenopathy

Question 38

What are the common causes of pharyngitis?

Answer 38

S. Pyogenes, rhinoviruses- about 50/50 each, Then Influenza Then EBV

Question 39

How can you differentiate between S. pyogenes and viruses for the causes of sore throat

Answer 39

Pyogenes causes a more severe illness with fever, pain, dysphagia and adenopathy, as well as a focal pharyngeal infection Viruses oftena ffect nose and throat, with hoarse voice, cough etc. but a less severe illness

Question 40

Describe S pyogenes as a bacteria

Answer 40

Gram positive Beta haemolysis Serogroup A

Question 41

Describe haemolysis and serogrouping

Answer 41

Haemolysis- a haemolysis will show green blood b haemolysis willl show clear g haemolysis will show nothing Lancefield serogrouping means that antibodies will do different things to different streps

Question 42

Describe infection with S pyogenes

Answer 42

Asymptomatic colonisation occurs in about 30% of nz population Does give risk of rheumatic fever Get sick soon after infection, but can stay as an asymptomatic infection for several months. Can have repeat infections as different types have different M type surface receptors

Question 43

Describe colds

Answer 43

Nasal discharge from ant and post nose, with nasal congestion Facial congenstion, fullness, pain and pressure Reduced or absent smell Fever

Question 44

Describe the causes of sinusitis

Answer 44

90-98% caused by viruses- rhinovirus, influenza, parainfluenza Bacteria cover the rest- strep pneumoniae and haemophilus influenzae. Can only be confirmed by sinus aspiration

Question 45

Give a general overview of causes and consequences of URTIS

Answer 45

Mostly caused by viruses but may be caused by bacteria- very difficult to distinguish Minimal benefit from antibiotics, but a very common cause of wasteful antibiotic treatment!

Question 46

What is cellulitis and how does it present?

Answer 46

An infection of the dermis and subcutaneous tissue, often seen around injury site or deep abscess. Presents and diffuse with small abscesses

Question 47

Describe impetigo and erysepelas

Answer 47

Impetigo- Pus filled lesions, which crust over. Very contagious Erysepelas- Acute infection of upper dermis and superficial lymphatics, presents with a clear line between healthy and inflamed skin

Question 48

Describe the inflammatory response to bacterial infection

Answer 48

Bacteria enters a wound Platelets release blood clotting proteins at wound site- this is important for containment of infection Mast cells mediate vasodilation for delivery of blood, plasma and cells to injured area by releasing heparin and histamine Innate immune mechanisms PAMP and compliment activate residential macrophages Neutorophils degrade and kill pathogens Neutrophils and macrophages phagocytose debris Macrophages secrete cytokines that attact immune cells and activate tissue repair cells This continues until the foreign material is eliminated and wound repaired

Question 49

Give an overview of PAMPS

Answer 49

Pathogen associated molecular patterns- recognized by pattern recognition receptors on the surface of macrophages to recognize most common receptors on gram positive and negative bacteria- LPS is most common negative one

Question 50

Describe diapedesis

Answer 50

Leukocytes travel through blood vessels, which have increased adhesion molecule expression (e. selectin). This slows neutrophils to a roll. The vessels have open endothelial junctions allowing cells to squeeze through, and follow a chemotactic gradient.

Question 51

What organisms can cause skin/subcutaneous tissue infection?

Answer 51

Strep pyogenes Staph aureus Viruses Some other bacteria and fungi

Question 52

Describe Streptococcus

Answer 52

Gram positive, catalase negative. Causes SSTI, systemic diseases, pharyngitis and potentially rheumatic fever. Group A serotype Found exclusively in humans.

Question 53

How does S pyogenes interact with the immune system?

Answer 53

it has with MSCRAMMS (microbial surface components recognising adhesive matrix molecuse), which are cell wall attached adnesins that bind to host ECM proteins. It has a hyaluronic acid capsule to prevent opsonisation and phagocytosis, M proteins (MSCRAMMS), secretes toxins - Streptolysins lyse immune cells C5a peptidase prevents cheotaxis DNAses degrade neutrophil extracellular traps SpyCEP also prevents chemotaxis

Question 54

How does S pyogenes spread?

Answer 54

Proteases, lipases, hyaluronidase and streptokinase help it to degrade tissues and move further in Streptokinase is an anticoagulant that activates plasminogen to cleave fibrin plugs If it gets deep enough it can cause necrotising fasciitis

Question 55

How do you diagnose the cause of skin infection?

Answer 55

Swab purulent materia, do a culture | Also do a blood cultures- if positive, can cause further complications

Question 56

How do you determine the category of bacteria?

Answer 56

Gram positive ar staph and strep Catalase test shows bubbling of H2O2 with staph, but not with strep Haemolysis can show part, full or no results Bacitracin susceptibility determines between groups A B and C strep

Question 57

How do you treat SSTIs?

Answer 57

Supportive care, rest and elevation, analgesia, antimicrobial drugs (s pyogenes is susceptible, but staph needs to be treated with a b lactamase resistant penicillin All pyogenes are susceptible, but only 10% of aureus are.

Question 58

How does penicillin work?

Answer 58

``` It binds to and prevents functioning of the transpeptidase enzyme, which cross links alternating sugars in the bacterial cell wall- this results in a weak, easily lysed cell wall They are a group of B lactam antibiotics, with each class having different side chains ```

Question 59

What are the distinguishing features between bronchitis and pneumonia?

Answer 59

Pneumonia shows focal signs in the lungs as well as rep distress. It causes increased resp rate due to hypoxia and nociception, crackles, consodilation, fevers and chills They can be differentiated by chests on X ray and tests of sputum Normal chest X ray will be able to follow the lung margins and follow the heart There will be shadowing and pleural effusion in pneumonia cases

Question 60

What are risk factors for pneumonia?

Answer 60

Smoking- damages cilia Age <2 or >65- larger number of bacteria in the lower lung aspirated from the nasopharynx hronic lung disease Immune dysfunction

Question 61

What are some of the defence mechanisms of the airways?

Answer 61

``` Ciliated epithelium Nasal turbinates Nasal secretions Saliva Epiglottis Goblet cells Airway lysozymes PAMs Surfactant Neutrophils ```

Question 62

What are the most likely causes of pneumonia?

Answer 62

Strep pneumoniae (3/4 of cases) Haemohilus influenzae Staph Aureus

Question 63

Describe streptococcus pneumoniae

Answer 63

Alpha haemolytic streptococcus group Colonises the nasopharynx in 5-10% of adults 20-40% of children. prevalence increases in winter Can cause pericarditis and endocarditis

Question 64

Describe the virulence factors of strep pneumoniae

Answer 64

Surphase protein A binds to epithelial cells and prevents deposition of C3b Choline binding protein binds to Ig receptor on epithelial cells, allowing transport into the cell Pneumolysin lyses neutrophils Polysaccharide capsule prevents phagocytosis and complement deposition Pili contribute to colonisation and cytokine production Surface protein C prevents activation of complement

Question 65

What is pneumococcal disease?

Answer 65

An infection of spinal fluid by strep pneumoniae

Question 66

What are the possible tests for pneumonia and describe some

Answer 66

``` CXR Sputum culture- but easily contaminated Nasopharyngeal swab if admitted Blood cultures if admitted Urite ICT- lacks sensitivity Serology ```

Question 67

What is treatment of pneumonia?

Answer 67

Antibiotics required for reduced duration and risk of death However, penicillin resistance is increasing- unlike MRSA, it can be partially susceptible Oral dosing may be inadequate, with IV dosing best

Question 68

How can antibiotics target ribosomes?

Answer 68

``` Prevents protein synthesis May target transpeptidation (macrodiles) Peptidyl transferase Initiation TRNA binding ```

Question 69

Describe macrolides and why they may present issues

Answer 69

They are a broad spectrum antibiotic with limited activity against gram negative bacteria. Theya re acctive against trep, staph and other causes of pneumonia, as well as chlamydia Can cause GI upset as they increase peristalsis, as well as sudden death (change electricity of heart) and drug interaction

Question 70

What is anaemia?

Answer 70

A reduction in the concentration of haemoglobin in the peripheral blood below the normal for the age and sex of the patient.

Question 71

What are the two different ways of classifying anaemia?

Answer 71

Pathologically- based on the cause of the anaemia. Can be impaired red cell formation, blood loss or excessive haemolysis, or a mix Morphological classification- based on red cell appearance, mean cell volume, or mean cell haemoglobin concentration

Question 72

Describe normocytic anaemias

Answer 72

The MCV is within the normal range, also usually normochromic with a normal MCHC (although mild hypochromia may also be present)

Question 73

Describe hypochromic microcytic anaemia

Answer 73

MCV is reduced, and MCHC is reduced. Often due to iron deficiency

Question 74

Describe macrocytic anaemias

Answer 74

MCV is increased. Most are normochromic but some mild hypochromia can also occur.

Question 75

What kind of lab tests can be done to determine anaemia's presence and cause?

Answer 75

``` Red cell count PCV MCV MCHC Also helped by blood film appearance, bone marrow biopsy, presence of other blood cells ```

Question 76

What are some of the causes of impaired RBC production?

Answer 76

Deficiency of substances needed for production (Iron, B12, folate) Genetic defect- thalassemia Failure of bone marrow- infiltration by cancer, radiation or drugs

Question 77

What are some causes of reduced RBC survival?

Answer 77

Blood loss- can be acute, but also can be slow, chronic loss (ie occult bleeding from the gut) - Haemolysis increased due to environmental or intrinsic RBC production. This also shows jaundice due to increased bilirubin.

Question 78

What are the causes of microcytic hypochromic anaemias?

Answer 78

Iron deficiency Chronic illness causing iron block Genetics (thalassemia)

Question 79

How do the causes of microcytic anaemia cause this disorder?

Answer 79

Iron deficiency and chronic inflammation mean iron is reduced in its transport, causing less haem formation, or else not delivered from the stores to the haemoglobin Thalassemia causes mutation meaning that either the alpha or beta globin chains are insufficient.

Question 80

How do you diagnose iron deficiency?

Answer 80

Measure the serum iron, binding capacity (transferrin) and iron saturation, as well as serum ferritin (stored form of iron) Rarely need to examine iron stores Remember that anaemia is a late consequence of iron deficiency

Question 81

What can iron studies tell us about potential diagnoses?

Answer 81

In iron deficiency, we will see low ferritin, low serum iron, high iron transport protein, and low iron saturation In chronic disease anaemia, we will see normal ferritin concentration, low serum iron, low transport protein and normal saturation In iron overload we will see high serum ferritin, high serum iron, and low iron transport.

Question 82

What are some potential causes of iron deficiency>

Answer 82

Diet Malabsorption (loss of proximal small bowel function) Increased demand (pregnancy) Chronic occult blood loss (GI or GU tract

Question 83

What are the most common forms of iron deficiency for different groups, and how do we treat them?

Answer 83

Premenopausal women: Imbalance between intake and menstrual blood loss of iron Children: Dietary Males/post menopausal females: Occult blood loss from GI tract Treated with oral iron replacement therapy Sometimes can see GI toxicity with constipation and diarrhoea. Can also give IV infusion Should see Hb increase 20g/L per 3 weeks

Question 84

Describe how anaemia of chronic inflammation can cause microcytic anaemia

Answer 84

It results in an iron block. It shows adequate iron storage, but this is retained in macrophages and marrow, rather than being given to erythrocytes. It also causes reduced free iron to prevent bacteria from using it Hepcidin produced in the liver normally stops iron transport from the macrophages to the serum. It is upregulated by cytokine IL6, and blocks absorption and release from macrophages

Question 85

Describe how thalassemia can cause microcytic anaemia

Answer 85

It is a mutation in alpha and beta globin. Can be widespread. causes 1 or both alpha or beta chains to not be present Heterozygotes have mild form, while homozygones have the severe form, necessitating lifelong transfusion. Untreated presents with hepato and splenomegaly, as well as bone marrow expansion to other sites Diagnosed by microcytic anaemia with exclusion of iron issue. Can then use haemoglobinopathy, and potentially other genetic testing

Question 86

What can cause macrocytic anaemia?

Answer 86

B12 deficiency Folate deficiency Liver disease, hypothyroid, excess alcohol

Question 87

What can the consequences of low B12/folate be?

Answer 87

Impaired DNA synthesis Affects all cell lineages if severe, but anaemia comes first Diagnosed by serum B12 and folate levels.

Question 88

What can cause low B12?

Answer 88

Diet (uncommon) Malabsoprtion due to gastrectomy, or immune issue (pernicious anaemia where antibodies against parietal cells/ intrinsic factor are produced) (body has stores of 3-4 years, so can take a while to present)

Question 89

What is haemolytic anaemia?

Answer 89

Anaemia due to increased destruction of red cells Presents with pallor, jaundice, splenomegaly Labs find raised bilirubin, reduced haptoglobins (proteins mopping up Hb- will all be taken up) Also features of increased RBC production (reticulocytosis) Also damaged red cells

Question 90

How can haemolytic anaemia be classified?

Answer 90

Intrinsic red cell defects- usually hereditary, eg. membrane defects Environmental, acquired- usually autoimmune Shortened survival

Question 91

What are the different categories of leukocytes?

Answer 91

- Phagocytes- include granulocytes (neutrophils, eosinophils and basophils) plus monocytes. Normally only mature phagocytes are seen in the blood - Lymphocytes

Question 92

Describe neutrophils

Answer 92

They circulate in the blood for 6-10 hours before moving into the tissues. They have a dense nucleus with 2-5 lobes and pale cytoplasm ith many pink or violet granules. These are termed primary in the promyelocyte stage, and secondary, appearing in the mature neutrophils. Primary granules contain lysosomal acid, enzymes and acid hydrolases, while secondaries contain lysosyme and acid phosphatase.

Question 93

What are the precursors of neutrophils?

Answer 93

Earliest recognizable is the myeloblast, which gives rise to promyelocytes, with primary granules, and then myelocytes, which have secondary granules. These then form metamyelocytes, then a band form of neutrophil, and finally mature neutrophils

Question 94

Describe monocytes

Answer 94

Larger than other leukocytes with a large central oval indented nucleus + clumped chromatin Cytoplasm is abundant and stains pale blue with many fine vacuoles. Granules often present. Precursors are difficult to distinguish from myeloblasts and monocytes

Question 95

Describe eosinophils

Answer 95

Similar to neutrophils but with coarser, redder granules and bilobed nuclei.

Question 96

Describe how eosinophils function

Answer 96

Function like neutrophils in that they are ameboid in motion and phagocytoze bacteria, particles and antigen-antibody complexes. Attractic by eosinophil chemotactic factor of anaphylaxis and histamine, released by mast cells and basophils. Also bind to parasites and respond to complement. Can clamp down allergic/hayfever reactions and so are prominent in these conditions

Question 97

Describe basophils and mast cells

Answer 97

- Basophils are found in small numbers with deep blue granules overlying the nucleus. Basophils are predominantly in the circulation and mast cells in the tissue Both have IgE attaachment sites, and when cross linked by an allergen it results in degranulation and histamine release, causing allergy symptoms

Question 98

Describe lymphocytes

Answer 98

Most are small cells with scanty cytoplasm and a central nucleus with coarse chromatin. Produced in the bone marrow and thymus. Larger lymphocytes can appear in peripheral blood, if challenged by antigens.

Question 99

How is granulopoiesis regulated?

Answer 99

They arise in the marrow from myeloid cells, take 6-10 days to mature, 6-10 hours to circulate and then move into tissues Regulated by GCSF particularly, which can be used post-chemotherapy and in congenital neutropenia to reduce the time taken to produce granulocytes.

Question 100

How are monocytes regulated?

Answer 100

Mature in the bone marrow in 6 days, then circulate for 20-40h. Enter the tissues and become macrophages Regulated by GM-CSF and M-CSF

Question 101

What are the different tissue-specific populations of macrophages?

Answer 101

Liver-Kupffer cells Lung- Alveolar macrophages Skin- Langerhans cells Brain- Microglial cells

Question 102

What are the overall functions of neutrophils?

Answer 102

Act against bacterial infections, performing phagocytosis, chemotaxis and antibody-dependent cell-mediated cytotoxicity

Question 103

What are the overall functions of monocytes/macrophages?

Answer 103

Act against parasitic, protozoal, fungal infections as well as tumours Perform immune surveillance, phagocytosis, chemotaxis, cytotoxicity and antigen presentation

Question 104

Describe chemotaxis

Answer 104

Phagocyte is attracted to the bacterir or site of inflammation by chemotactic substances released by damaged tissues, bacteria, prostaglandins, products of fibrinolytic and kinin genetrating systems, and complement components.

Question 105

Describe phagocytosis

Answer 105

The foreign material or dead/damaged cells of the host's body are phagocytosed. Recognition of the foreign particle is aided by opsonisation with Ig or complement, as neutrophils and monocytes have surface receptors for the Fc components of Ig and C3/other complement proteins

Question 106

Describe cell killing

Answer 106

Occurs by oxygen dependent and independent pathways Dependent: Superoxide and H2O2 are generated from O2 and NADPH. This reacts with myeloperoxidise and halides to kill the bacteria Non oxidative involves a fall in pH within phagocytic vacuoles into which lysosomal enzymes are released

Question 107

What can cause neutrophil leukocytosis?

Answer 107

Refers to an increase in neutrophils, often associated with a shift to the left where there are more immature cells in the blood Occurs reactively, due to bacterial infection, trauma, inflam, blood loss

Question 108

What can cause neutropenia?

Answer 108

Low neutrophil count Caused by congenital syndromes, drugs, immune issue, viral infection, recurrent infection Rarely it is due to neutrophil functional defects

Question 109

What can cause eosinophilia?

Answer 109

Caused by allergic and parasitic reactions

Question 110

What can cause monocytosis?

Answer 110

Chronic bacterial infections | Malignancy

Question 111

How o lymphocytes form and what are their types?

Answer 111

Lymphoid stem cells go to lymphoblasts go to lymph cells | Can be B, T cells or NK cells

Question 112

What are the primary lymphoid organs and what occurs here?

Answer 112

``` Bone marrow (maturation of B cells) and thymus (maturation of T cells) Lymphocytes acquire their repertoire of antigen receptors and learn to discriminate between self and nons elf ```

Question 113

What are some secondary lymphoid organs and what occurs here?

Answer 113

Include lymph nodes, spleen, and areas like peyer's patches | Lymphocytes migrate here. This is where antigens are presented

Question 114

Describe how the spleen functions in immunity

Answer 114

Spleen contains red pulp for removal of old red cells, and white pulp containing lymphoid tissue. This tissue is arranged around a central arterial, termed the periarteriolar lymphoid sheath (PALS) T cells are found directly surrounding it while B cells are beyond this.

Question 115

What can cause lymphocytosis?

Answer 115

Seen in viral infections in adults, malignant issues (chronic lymphocytic leukaemia) or in infants and young children in response to infection

Question 116

What can cause lymphopenia?

Answer 116

bone marrow failure, steroids, HIV, immunodeficiency syndromes Assoc. with increased risk of opportunistic infection

Question 117

What can cause lymphadenopathy>

Answer 117

Viral infection, local bacterial infection, lymphoma or metastatic cancer

Question 118

How are megakaryocytes produced?

Answer 118

It matures by a process of endomitotic synchronous nuclear replication, forming enlargement of the cytoplasm and increasing the number of nuclei by multiples of 2. Mature megakaryocytes contain 16-32N They then show cytoplasmic differentiation with production of fibrinogen, factor V, platelent factor 4, von willebrand factor, PDGF and glycoproteins

Question 119

How do platelets develop from megakaryocytes?

Answer 119

An extensive membrane system called demarcation membranes is formed by invagination of the plasma membrane. THe mature megakaryocyte is located next to bone marrow endothelial cells, and develops filopodia that extend into marrow capillaries. These then fragment to release mature platelets (approx. 4000 per megakaryocyte)

Question 120

What regulates the production of platelets?

Answer 120

Thrombopoietin (TPO). Some contribution from steel factor, IL-6 and IL-11

Question 121

How long do platelets last and how are their levels maintained in the body?

Answer 121

7-10 days. About 1/3 is kept in the spleen. | Consumption is by senescence and utilization

Question 122

Describe the structure of platelets

Answer 122

Discoid cells with an intricate system of channels continuous with the plasma membrane. This large surface area allows selective absorption of plasma coagulation proteins Glycoproteins on the surface coat allow adhesion and aggregation Submembranous area contains contractile filaments, and circumferential microtubules maintain the discoid shape.

Question 123

Describe the platelet cytoplasm

Answer 123

Have 3 distinct types of secretory granules, containing calcium, magnesium, ADP, ADP and vasoactive amines including serotonin Alpha granules contain coagulation factors, platelet derived growth factor, TGF-B, heparin antagonist, and other proteins Lysosomes contain hydrolytic enzymes Energy is provided by oxidative phosphorylation in mitochondria and utilization of platelet glycogen in anaerobic glycolysis

Question 124

What is primary haemostasis?

Answer 124

The process of forming a platelet plug at the site of vessel injury

Question 125

What are the three main phases of platelet function?

Answer 125

Blood vessel constriction then aggregation to form a loose platelet plug, then the clotting pathway stabilizes the plug

Question 126

Describe how platelets adhere to foreign surfaces and aggregate.

Answer 126

They adhere to exposed subendothelial collagen, and need to be supported by von Willebrand factor. VWF adheres to the collagen, causing it to undergo a conformational change, and bind to specific receptor sites called glycoprotein Ib IX V on the platelets. This rolls the platelet to the vessel wall, causing platelet shape change and activation The granules are released to activate more platelests The shape change also exposes integrin a IIb B3 receptors, which sticks to VWF and other platelets Prostaglandin synthesis causes thromboxane A to be produced, activating coagulation reactions and producing thrombin, recruiting other platelets and forming and obstructive plug Cofactors like fibrinogen binds these integrin receptors together.

Question 127

What are the functions of thromboxane A2 and how is it released?

Answer 127

Potentiates platelet aggregation, with powerful vasoactive activity Inhibited by substances such as prostacyclin, which increases cAMP in platelets, sythesised by vascular endothelial cells. This prevents deposition on normal endothelium Aspirin inhibits A2 production, allowing increased bleeding to happen

Question 128

What do ADP, fibrinogen and serotonin do in coagulation?

Answer 128

ADP and fibrinogen result in secondary aggregation by binding to receptors on the platelet surfaces. . serotonin mediates vasoconstriction.

Question 129

What are some platelet-vessel wall interactions that control haemostasis

Answer 129

Tissue factor initiates coagulation Prostacyclin and NO cause vasodilation, and hihibit platelet aggregation VWF causes the platelet collagen adhesion and carries factor VIII Antithrombin, and protein C inhibit blood coagulation Tissue plasminogen activator causes fibrinolysis

Question 130

What are some causes of thrombocytopenia?

Answer 130

Reduced production due to viral infection, drugs or bone marrow failure. Aplastic and leukaemic failure are typically pancytopenic. Carcinoma and megaloblastosis cause it in isolation Increased destruction due to immune thrombocytic purpura, autoimmune disorders, drugs, DIC, hypersplenism, transfusion or viral infection

Question 131

What can cause thrombocytosis?

Answer 131

Increased production, either due to infection, inflammation or myeloproliferative disorders

Question 132

Describe immune thrombocytopenia

Answer 132

Acute history of epistaxis, bruising, no lymphadenopathy or hepatosplenomegaly (showing no chronic issues) Need to exclude other vauses like viral illness, drugs, bone marrow issues If severe, treated with prednisone. This is normally enough for 2/3 of the population. If not, or it causes relapse, splenectomy helps in 3/4 of this population. The minority don't respond to either treatment, and need thrombopoetin receptor agonists- but this is an expensive lifelong treatment

Question 133

Describe platelet clumping as an artefact

Answer 133

Some people's platelets rect to the anti-clot factor in test tubes and clump, causing the appearance of thrombocytopenia

Question 134

Define petichiae, purpura and ecchymoses

Answer 134

Petichiae- pinprick bleeds Purpura- normal bruising Ecchymoses- huge bruises

Question 135

What is innate immunity?

Answer 135

Our physical barriers to infectious agents, our microbicidal factors in body fluids, and our phagocytic cells

Question 136

What is the difference between effector and regulatory immune responses?

Answer 136

Effector responses involve antibody production, antigen specific cytotoxicity, ADCC and NK cells Regulatory responses involve cytokines, TH cells and Treg cells

Question 137

What are MHCs?

Answer 137

``` Major histocompatibility groups Can be class I, controlled by genes HLA A/B/C inhumans and are found on all nucleated cells Can be class II, controlled by genes HLA DP/DQ/DR. Found on professional antigen presenting cells and B lymphocytes ```

Question 138

What promotes phagocytosis by neutrophils?

Answer 138

Bacterial cell wall components (weak) C3b complement components (high affinity) Fc region of antibodies (immune mediated opsonisation)

Question 139

What can the innate immune system recognise?

Answer 139

Pathogen associated molecular patterns recognized by pattern recognition receptors (PAMPs and PRRs) These recognise - common cell wall structures including lipopolysaccharides and peptidoglycans - bacterial metabolic products like N formylmethionine peptides (f-Met-leu-phe, formed by prokaryocytes exclusively) - heat shock proteins released by stressed cells These lead to danger cells alerting systems to do something

Question 140

What are acute phase proteins?

Answer 140

Plasma proteins produced early in infection as a response to alarm mediators like IL-1. Many are produced in the liver. They act to enhance host resistance, minimize tissue injury, promote resolution and repair of lesions, and form part of the complement cascade

Question 141

Give an overview of the different adaptive immune cells

Answer 141

B cells produce antibodies NK cells do ADCC to function in early anti viral and tumour immunity TH1 function in viruses and bacteria, with TH2 in parasites and allergies (intra vs. extracellular) TH17 does mucosal surfaces and inflammatory processes Treg down regulates inflammation 90% of these sit in the nodes, spleen and tonsils/adenoids/peyer's patches

Question 142

Describe lymphocyte circulation

Answer 142

about 10% circulate at any time They can migrate from the blood into the tissue through high endothlial venules, or can leaves into the lymph nodes They can then recirculate through the lymphoid system back to the blood, moving through lymphoid organs where they can contact processed antigens Not all classes circulate to the same extent

Question 143

How do antigens meet the adaptive immune system?

Answer 143

Non infectious is treated differently to infectious Intracellular agents will be treated differently to extracellularly They are taken up by APCs, leave and enter the lymph system, are transported to lymph nodes and presented to nodal lymphocytes

Question 144

What are the functions of APCs?

Answer 144

Collection, concentration, processing and presentation of antigens Co stimulation via cytokines and accessory surface molecules Induction of tolerance by teaching the immune system to tolerate particular antigens

Question 145

What is the endogenous pathway of antigen processing?

Answer 145

Done by class I MHC receptors Cytosolic proteins are degraded into fragments by proteosomes Peptides are inaccessible to MHC molecules, which are still bound on the ER Peptides are transported to the ER lumen and inspected by TAP bound MHC When a peptide binds tightly, the MHC folds around it and is transferred to the cell membrane

Question 146

What is the exogenous pathway of antigen presentation?

Answer 146

Antigen is taken up from outside the APC into intracellular vesicles. Acidification of vesicles activates proteases to degrade the antigen into peptide fragements Vesicles containing these fragments fuse with MHCII vesicles, and peptides with an affinity bind This peptide is transported to the surface by the MHCII

Question 147

Describe myaesthenia gravis

Answer 147

Autoimmune response against ACh receptors, causing defects at the NMJ- eg. causing diplopia at the eyes Also presents with fatigue, weakness and dysarthria

Question 148

Describe the pathway of platelet activation

Answer 148

Vessels vasoconstrict, reducing blood flow to the site of injury. Platelets stick to the exposed collagen via VWF, which attaches the GpIb receptor to the collagen. Aggregation follows, causing a shape change from a disc to a spiney sphere. This also causes release of vasoconstricting amines and adenine ucleotides that cause further activation of platelets, and initiate aggregation. Aggregation is mediated by fibrinogen, which binds platelets together via integrin aIIb B3.

Question 149

Desribe the coagulation cascade

Answer 149

The second stage of haemostasis, involving proteins rather than cells The activation of coagulation causes formation of fibrin, which webs around the platelet plug, stabilising the clot. The role of the coagulation pathway is in the generation of thrombin, which converts fibrinogen to fibrin. The pathway can be activated by contact activation on a charged surface, or one involving tissue factor (most physiologically relevant)

Question 150

Define thrombosis

Answer 150

Formation of an abnormal thrombus when vessels wall is intact.

Question 151

What is the difference between the makeup of venous and arterial thrombi?

Answer 151

Venous are formed of red cells and fibrin | Arterial are formed of platelets

Question 152

What is the importance of cofactors in the coagulation cascade?

Answer 152

They line up substrates with their proteases, so that the binding sites fit together and can react

Question 153

Give the steps of coagulation

Answer 153

Initial burst 1. Tissue factor is exposed on the subendothelial tissues. 2. Factor VII binds to TF, and changes shape to prep for activation 3. Activated VII activates X to Xa, IX to IXa. 4. Process is rapidly turned off by Tissue Factor Pathway Inhibitor, which accumulates due to platelet activation and binds to Xa and the VIIa complex Thrombin Feedback 5. Factor Xa has already converted a small amount of prothrombin to thrombin, in the presence of phospholipid to help binding, and calcium for shape control 6. Thrombin amplifies the coagulation pathway by activating V, VIII (increase speed) and XI 7. VIIIa, IXa, Ca and Phospholipid form a complex, which converts more X to Xa 8. Xa complexes with Va, Ca and Phospholipid, which rapidly convert prothrombin to thrombin 9. Thrombin converts fibrinogen to fibrin, as well as activating XI, which converts IX to IXa. It also activates factor XIII, which stabilises the chains (deficiency causes bleeding due to clot breakdown) 10. The fibrin is cross linked together, which forms a stable web.

Question 154

Describe the intrinsic pathway

Answer 154

Involves spontaneous conversion of XII to XIIa after contact with a negatively charged surface. XIIa activates XI and IX, initiating coagulation as above. It is linked to the bradykinin pathway Deificiency of XII doesn't necessarily cause bleeding because it is mainly relevant for lab tests However, it can be activated by the presence of central lines

Question 155

What are the contact factors involved in the coagulation cascade?

Answer 155

XII, XI, and two factors in the intrinsic pathway

Question 156

What are thrombin sensitive factors in the coagulation cascade?

Answer 156

Fibrinogen, V, VIII, XIII

Question 157

What are the vitamin K dependent factors in the coagulation cascade?

Answer 157

II (thrombin), VII, IX, X These all have a Gla domain held in shape by Ca2+ These need to be gamma carboxylated, which needs Vit K Warfarin inhibits vit K, which increases bleeding risk The same occurs in liver disease, and newborns, as these proteins are produced in the liver

Question 158

What are the roles of thrombin?

Answer 158

``` Activations of Platelets VIII V XI Fibrinogen to fibrin by removing the a / b chains from the end and allowing cross linkage XIII cross linkage of fibrin Protein C ```

Question 159

What are the inhibitors of the coagulation cascade?

Answer 159

Antithrombin Protein C Protein S TFPI

Question 160

Describe the action of antithrombin

Answer 160

Inhibits thrombin by forming a 1:1 complex. Also inhibits factor Xa and IX / XI

Question 161

Desribe the action of protein S and C

Answer 161

C is activated to form activated protein c (APC) by thrombin in the presence of thrombomodulin (found in endothelial cells). S is a cofactor that enhances its action These inactivate factors Va and VIIIa

Question 162

Describe the actions of the fibrinolytic system

Answer 162

Digests the clot so that normal vessels structure can re-emerge Converts plasminogen to plasmin using tPA and uPA This causes the clot to turn into D dimers, and fibrinogens into fibrinogen degradation products- seen in high levels in inflammation and clot formation

Question 163

What inhibits fibrinolysis?

Answer 163

Antiplasmin forms a 1:1 complex with plasmin Thrombin activated fibrinolysis inhibitor (TAFI). Activated by thrombin in the presence of thrombomodulin, and remvoes lysine from fibrin, preventing plasminogen from binding to the clot

Question 164

Describe the different haematologic malignancies

Answer 164

Myeloproliferative disorders like polycythaemia- mutation in stem cells causing proliferation of 1 or more types. show elevated RBCs, haematocrit and platelets Lymphomas- enlarged lymph nodes- can be reactive, immune, cancer or metastasised cancer Plasma cell disorders like myeloma- cancer of plasma cells causing lytic lesions in bones Leukaemia

Question 165

Describe leukaemia

Answer 165

Results from accumulation of abnormal, immature WBCs in the bone marrow, replacing normal elements and spilling over into the blood, resulting in marrow failure Anaemia, thrombocytopenia neutropenia, leukocytosis and infiltration of other organs Can be myeloid or lymphoid in origin

Question 166

What are the different leukaemias?

Answer 166

Acute- rapidly progressive ALL- due to B or T cell proliferation AML- subtypes based on genetics, phenotype and morphology Chronic- initially slow CML- myeloproliferative disorder CLL- related to lymphomas. Common in older people. Show palapable nodes and spleen, leukocytosis and smear cells

Question 167

What are the clinical features of the acute leukaemias?

Answer 167

Bone marrow failure, showing anaemia (pale and lethargic), neutropenia (fever, infection, slow healing) and thrombocytopenia (bruising and bleeding) Organ failure, showing tender bones, lymphadenopathy if lymphoid, hepato and splenomegaly, gum hypertrophy etc

Question 168

What are the lab findings of acute leukaemias?

Answer 168

Normochromic anaemia Increased WBC with blasts Thrombocytopenia Hypercellular bone marrow with >20% leukaemic blasts

Question 169

What are the causes of leukaemia?

Answer 169

Chromosomal issues- philadelphia chromosome (translocation between BCR and ABL on 9 & 22, forming a fusion protein that switches on downstream pathways), acquired mutations causing impaired differentiation and maturation, increased proliferation Predisposing factors include radiation (including for other tumours), familial issues, viral infections, aldylating agents, down syndrome Most are idiopathic Gene discovery can help prognosis and therapy decisions

Question 170

How are acute leukaemias managed?

Answer 170

Supportive care and cytotoxic therapy - Red cell transfusions, platelets and antibiotics (need indwelling central catheters) Cytotoxic drug therapy can be for remission, consolidation (mop up leukaemic cells) or maintenance (if ALL) ALL usually includes prophylaxis as there is increased relapse- so an easier but longer course AML is shorter but more intense

Question 171

Where do you source bone marrow transplants for leukaemic patients?

Answer 171

CCan have autologous- own cells when in remission | Allogenic- donated from sibling or unrelated. Can be from marrow, peripheral blood or cord blood.

Question 172

What are the three main coagulation factor screening tests?

Answer 172

APTT PR TCT

Question 173

Describe the APTT

Answer 173

Performed by collecting venous blood in citrate, which removes Ca2+ to stop clotting in the tube Sample is spun and plasma is collected Addition of an activator, phospholipid and Ca2+ Measure the time taken for a clot to form

Question 174

What does the APTT measure?

Answer 174

All factors except factor VII, but is most sensitive to XII nad XI Commonly prolonged in haemophilias due to lack of VIII / IX

Question 175

What is a 1:1 APTT and what does it indicate?

Answer 175

A repeat of the test done with a mixture of known normal plasma It will correct with factor deficiency It will not correct with lupus anticoagulant (possibly due to an antiphospholipid syndrome), acquired factor inhibitors, heparin, or dabigatram Not measuring natural inhibitors like protein C/S, antithrombin

Question 176

Describe lupus anticoagulant

Answer 176

An antibody mediated antiphospholipid syndrome that occurs transiently in unwell patients It doesn't cause bleeding as they bind to phospholipids and interfere with clotting in the lab only

Question 177

Describe the PR test

Answer 177

Ratio of prothrombin time to clot divided by normal clotting. It should be between .8-1.2 Performed by adding tissue factor to platelet poor plasmia in the persence of calcium Sensitive to vitamin K dependent factors, so useful in calculating INR for warfarin monitoring and looking at liver function

Question 178

Describe the TCT test

Answer 178

Adding thrombin to platelet poor plasma and measuring time for clot formation- normal depends on the conc of thrombin used Test only measures concentration or function of fibrinogen in the plasma. Also sensative to heparin, dabigatrain, FDPs

Question 179

How does heparin cause prolonged APTT?

Answer 179

It upregulates antithrombin, but corrects with a protease in the lab

Question 180

How does dabigatran cause a prolonged APTT?

Answer 180

It inhibits thrombin and doesn't react with protamine.

Question 181

Describe haemophilia A and B

Answer 181

They are X linked conditions with deformities in factor VIII (A) and IX (B). It severe cases, it can cause arthropathy, muscle bleeds, renal, GI, intracranial bleeding. This causes tissue and nerve damage, deformity, arthritis and joint destruction

Question 182

How is haemophilia treated?

Answer 182

Replacing the missing factor- almost always recombinants. Prophylactic is given in childhood to promote healthy joint development

Question 183

Describe Von Willebrand's disease

Answer 183

A defect of primary haemostasis, resulting from reduced or abnormal VWF. The screening test is platelet function assay. As it circualtes with factor VIII, this may also be reduced. Shows as mucosal bleeding, and rarely functional defects Commonly treated with DDAVP, which increases release of these components, or with plasma purified replacements in severe cases

Question 184

What can be told from PT combined with APTT?

Answer 184

Long APTT with normal PT must be factor VIII and IX deficiency if severe, XI if mild, or XII if asymptomatic Long PT with normal APTT must be factor VII (but occasionally can see mild deficiency in II, V, X and fibrinogen) Both long: Factors V, X, fibrinogen and thrombin, possibly multiple defect

Question 185

Describe multi-factor deficiencies

Answer 185

Due to - warfarin, or else vitamin K deficiency, causing factor II, VII, IX and X deficiency, with normal fibrinogen - Massive blood loss if also low fibrinogen - DIC- widespread coagulation activation causing thrombosis and then bleeding. Shows los factors as they are used up. Eg. meningococcal disease, as bacteria release toxins - Liver disease due to lack of production of all factors except VIII (as this is from endothelial cells)

Question 186

Describe virchows triad in relation to thrombi

Answer 186

Clots are caused by three mechanisms Stasis of blood flow, such as in immobility, pressure from a tumour or increased viscosity Hypercoagulability, such as in increased procoagulants or decreased inhibits, or changes to the vessel wall, like atherosclerosis, trauma, surgery, or prior thrombus

Question 187

What is hereditary thrombophilia and how can we test for it?

Answer 187

An inherited predisposition to blood clots- up to 1/2 of spontaneous cases are due to this Normally due to activated protein C resistance secondary to factor V gene mutation Factor V Leiden test: Direct DNA analysis. APCr is measured by coagulation based assay Factor V is resistant to cleavage by APC Can also be due to prothrombin 20210 mutation in promoter region, leading to excess prothrombin production Can also be due to antithrombin deficiency None of these are seen on regular coagulation tests

Question 188

How do we diagnose VTE/PE?

Answer 188

Include unilateral leg pain, swelling, discolouration and oedema PE shows shortness of breath, chest pain, tachycardia, tachypnoea and hypoxia High risk patients are tested further with radiology (ultrasound for DVT, CT for PE) Low risk patients have a D dimer test (breakdown product of fibrin)- if elevated, then onto imaging

Question 189

How de we treat VTE?

Answer 189

Anticoagulants including warfarin (reduces vit K factors but takes several days) If INR rises above 4 bleeding is at increased risk Heparin while we await warfarin's buildup. Often subcutaneous. Accelerates inhibition of activated thrombin and Xa. Requires antithrombin and heparin binds to it. Bleeding risk is higher in patients who are old, have renal impairment, prior haemorrhage or stroke, CHF or high alcohol intake

Question 190

How do we prevent bleeding in patients on warfarin

Answer 190

Warfarin can be easily reversed by IV vitamin K | Also can replace plasma coagulation factors (prothrombinex)

Question 191

What do dabigatran and rivaroxaban do?

Answer 191

Dabigatran- oral inhibitor or thrombin Rivaroxaban- inhibits Xa Would be used as warfarin has a large number of drug interactions These can be equal to warfarin for VTE and better in atrial fibrillation, with less IC haemorrhage. However, they are excreted renally and so aren't given to renal failure patients

Question 192

How do dabigatran and rivaroxaban alter the coagulation tests?

Answer 192

Dabigatran: TCT very long, and log APTT (1+1) and PR Rivaroxaban: Prolonged PR but APTT less so

Question 193

How do you reverse DOACs?

Answer 193

There is a monoclonal antibody that binds to dabigatran. Rivaroxaban doesn't have an antidote but can be helped by prothrombinex

Question 194

What is osteomyelitis?

Answer 194

Infection and inflammation of bone or bone marrow | Can be caused by skin/soft tissue infections as bacteria can arrive through the blood

Question 195

How does osteomyelitis occur?

Answer 195

Bacteria enter the bone through trauma, spreading from local infection or haematogeneously. They colonise and proliferate. Leukocytes infiltrate, and cause inflammation and formation of pus. Result is devascularisation, dead bone and abscesses. They can also invade bone cells and ivade immune responses They may also spread to the joint causing septic arthritis, especially if it occurs near a joint

Question 196

Who is at risk of osteomyelitis?

Answer 196

``` Diabetics with foot ulcers Patients with infections after trauma, bone surgery or joint replacement Root canal patients SSTI patients Children with chicken pox ```

Question 197

What are the bacteria that can cause osteomyelitis?

Answer 197

Staph aureus (most common) Strep pyogenes Group B strep (transferred by vaginal birth)

Question 198

How do you diagnose osteomyelitis?

Answer 198

Radiology (MRI confirms) Bone biopsy- specific but highly invasive) Blood sample if assoc with bateremia. Shows a high WBC, may be bacteria present

Question 199

What are the symptoms of osteomyelitis?

Answer 199

Pain, bone aches, redness, fever

Question 200

What are some lab tests that can determine bacteria of osteomyelitis?

Answer 200

Bacteria is gram positive for steph and strep, grm negative for others Catalase shows bubbles with staph and not with strep With staph, coagulase test is positive with aureus With strep, B haemolysis indicates pyogenes

Question 201

Describe staph aureus

Answer 201

Live transiently on skin and in nares of 20% of people Human to human transmission, commonly through community and hospital Causes SSTI, invasive disease, toxic shock. Gets under skin by cracks, splinters, hair follicles

Question 202

What are bacterial virulence factors?

Answer 202

Adhesins for binding to host tissue- called MSCRAMMs Spreding factors including staphylokinase, lipases, DNAses and cytolysins Immune evasion factors

Question 203

What are some immune evasion factors?

Answer 203

Cytolysins- lyce cells, leukocytes, erythrocytes Capsule- thick layer outside the cell wasll prevents opsonisation with Ig or C3b Slime layer (extracellular polysaccharide)- prevents antibiotics and immune components reaching the bacteria Protein A- binds IgG in the wrong orientation to prevent Fc reaching phagocytes, preventing opsonisation and phagocytosis Cell bound coagulase- binds prothrombin and induces fibrin polymerisation and deposition or the surface to prevent opsonisation and phagocytosis

Question 204

What are superantigens?

Answer 204

A faimly of heat resistant proteins that function as T cell mitogens to triger pro-inflam immune response Synergistic with endotoxin, and causes systemic inflammation with tissue destruction, vascular leakage, multiorgan failure and toxic shock

Question 205

How do you treat osteomyelitis?

Answer 205

Prolonged antibiotic treatment, although there is increasing resistance Possible surgical debridement

Question 206

Describe resistance to B lactam antibiotics

Answer 206

``` Resistant genes target part of the penicillin ring structure and deactivate it Methicillin cannot be destroyed by this, but there is now a class of staph that prevents it from binding, meaning it isn't recognized by penicillin. ```

Question 207

Describe impetigo

Answer 207

Infection of the skin from direct contact affecting young children, hot climates and areas of poor hygeine Secondary dermal spread by scratching is common

Question 208

What is the difference between folliculitis, furuncles and carbuncles?

Answer 208

Folliculitis is hair follicle infection with raised reddened follicle and pus Furuncle is an extension, with large, painful raised cutaneous nodules Carbuncle is a coalescence of furuncles, where the infection moves deeper and can cause systemic symptoms Treated with antibiotics and drainage

Question 209

Describe Staph scalded skin syndrome (ritter's disease)

Answer 209

Onset of perioral erythema moving to the whole body. Formation of large bullae, with no leukocytes. Affects neonates and young children

Question 210

Describe cellulitis

Answer 210

Rapidly spreading pyogenic inflammation of dermis after trauma, burn, surgery Area is tender, warm, red, swollen Risk increased by age, immune deficiency, diabetes

Question 211

Describe septic arthritis

Answer 211

Infection of joints, via the haematogenous, SSTI or trauma route

Question 212

Describe acute infectious endocarditis

Answer 212

Infection of inner heart tissue- mostly caused by S aureus

Question 213

Describe bacterial pneumonia

Answer 213

Inflammation of the lung after alveolar colonisation Can cause consolidation and abscess formation Necrotizing is a rare severe form caused by S aureus Most commonly due to S pneumoniae

Question 214

Describe toxic shock syndrome

Answer 214

Menstrual- caused by prolonged use of hyperabsorben tampons, allowing toxins into the blood via the vaginal mucosa Non menstrual- caused by superantigens as bacteria enter the blood through wounds and small cuts, causing systemic inflammation with high mortality

Question 215

Describe the structure of group A streptococcus

Answer 215

More than 100 types based on differing M proteins Fimbriae protrude through the capsule allowing adherence to epithelial cells Important active extracellular proteins from bacteria toxins and antigens

Question 216

Describe septic arthritis

Answer 216

Presence of infection from bacteria in bone and marrow / joint space. Occurs most frequently in childhood as they have predisposing growth plates. Symptoms include fever, malaise, swelling, erythema and tenderness, with the joint held in the position maximising intracapsular volume. Needs quick diagnosis but this can be difficult Diagnosed by joint aspirate Commonly S aureus and S pyogenes Needs drainage and washout with IV antibiotics

Question 217

Describe acute rheumatic fever

Answer 217

Occurs following throat infection with strep pyogenes, with a latent phase of several weeks Presents as generalised inflammation attacking the heart, joints, skin and brain Can cause damage to mitral/aortic valves in RHD

Question 218

What are the criteria for RHD?

Answer 218

2 major or 1 maj and 2 minor needed, plus evidence of preceding strep infection Major- carditis, polyarthritis, sydenhams chorea, erythema marginatum, subcutaneous nodules Minor- fever, polyarthralgia, RH history, raised CRP and ESR, prolonged PR interval

Question 219

How does RF produce arthritis?

Answer 219

Typically shows extremely painful joints unable to bear load, especially in the large joints Polyarthritis is asymmetrical and migratory It occurs as antibodies cross react with collagen or valvular endothelial antigens, then T cells infiltrate and cause damage Auto antibody mediated neuronal cell signalling in CSF may be part of chorea

Question 220

How do we test for strep?

Answer 220

Do antibody titres as msot ARF cases have a culture negative throat, and even when it is there it could represent carriage rather than confirming infection Use plasma antistreptolysin O and antideoxyribonuclease B titres ASO is highest 3-6 weeks post infection

Question 221

How do we treat ARF?

Answer 221

Use penicillin as streptococcus remains exquisitely sensitive to this IV has high speed, short action and a rapid high concentration Intramuscular injection has a low peak but a long duration of concentration, helpful for vascular areas

Question 222

What is the difference between septic arthritis and ARF?

Answer 222

SA occurs in any age groups with an active infection. Treated with clearing joint and using penicillin ARF occurs in school age and is an autoimmune antibody response to S pyogenes causing multisystem inflammatory disease. It is treated with penicillin in high dose and then prophylactically.

Question 223

Differentiate class I and class II HLA

Answer 223

Class I: HLA- DP/Q/R On all nucleated cells, and present peptides to CD8 CTcells Class II: HLA A/B/C On specialised APCs and B cells. Present antigens to CD4 Th cells Borth are codominantly expressed and polymorphic-

Question 224

Why is HLA important

Answer 224

They code for MHC receptors on cells, which present self and non self peptides. They determine our susceptibility to what we can and cannot respond to. This is because for immune activation to occur, we need to recognize peptides and MHC together

Question 225

What are some other structures involved in immune conversations?

Answer 225

Cell Surface Adhesion molecules- link cells together. Important in binding lymphocytes to APCs and directing lymphocytes and phagocytes to where they are needed. They are the first step in lymphocyte and T cell meeting Co-stimulator molecules- pass signals between linked cells through surface-surface interactions to trigger or inhibit antigenic effects Intracellular Cytokines- express specific cytokine receptors Hormones- modulate antigen activated cells

Question 226

What can happen if there is a defect in TAP genes?

Answer 226

Poor endogenous antigen processing Low HLA A/B.C Few CD8 cells with normal CD4 Recurrent respiratory viral infections as class 1 are required for CD8 cell function, which is crucial in resp infections.

Question 227

How do selectins help in immune communication?

Answer 227

They are adhesion molecules that show rapid association and dissociation. L are on leuocytes, P are in platelets, and E are on endothelial cells.

Question 228

How do integrins help in immune communication

Answer 228

Also adhesion molecules which match ligands called Ig superfamily molecultes. They show strong adhesion and help to maintain tissue integrity They have site specific adhesions to help direct cells around the body, and hold lymphocytes together for activation

Question 229

Describe how neutrophils move into the tissues

Answer 229

Endothelial cells with nearby infections epress more selectins and ligands to slow leukocytes where they are needed Spaces between the cells expand to allow ease of diapedesis Adhesion binding through selectins causes cells to roll This activates expression of integrins, which stronglyl bind and tether the cell, before it migrates through the capillary wall.

Question 230

Describe how co-stimulator molecules work using an example

Answer 230

Eg. B7 and CD28 B7 is only present on APCs when the antigen presented is foreign/dangerous. The helper T cells won't react unless B7 matches with CD28. An antigen presented without B7 causes anergy of the T cell, where it is paralysed to prevent self-reactivity

Question 231

Describe how co-inhibitor molecules work using an example

Answer 231

CTLA4 is expressed in regulatory T cells, but is up regulated in other T cells after activation. When it matches with B7 it acts as an off switch, binding with greater affinity that CD28 to enable it to compete for binding

Question 232

How do costimulator molecules help with B cell activation?

Answer 232

B cells express CD40, and if T cells have the appropriate CD40 Ligand, the trigger other processes, up regulating B cell B7, and causing its differentiation into memory and antibody forming cells

Question 233

Describe cytokines and give some of their main functions

Answer 233

They are chemical messengers produced by T helper cells. They move between cells- interleukins specifically move between leukocytes Can do pleiotropism- act on different cell types Used for redundancy with overlapping action Can do synergy where two or more work together Also have antagonistic actions where one inhibits the other.

Question 234

What are some of the important immune response cytokines?

Answer 234

Interferon a and b play important roles in interfering with viral replication. Cells detect that they are being used an increase interferon to cause transient viral resistance in nearby cells. It also acts on NK cells, promoting them to recognise and kill targets TNF and IL1/6 are important for bacterial infections as they produce a proinflammatory response. They are upregulated in early inflammation, and function for things like wound healing, tissue repair, fibroblast proliferation, bone resorption, prostaglandin and collagen synthesis, and neuroendocrine effects

Question 235

Describe chemokines

Answer 235

Produced at sites of inflammation promoting recruitment of neutrophils (IL8) or stimulating histamine release (MCP-1)

Question 236

What are haematopoietic cytokines?

Answer 236

Promote growth and differentiation of haematopoietic cells. Often termed CSFs Can be IL3 (multi CSF) G CSF, M CSF and GM CSF can stimulate granulocytes, monocytes or both IL5 stimulates eosinophils IL7 stimulates erythroblasts and megakaryocytes

Question 237

What are blood group antigens?

Answer 237

A series of glycoproteins and glycolipids present on the surface of RBCs. Their development is determined autosomally and codominatntly. They have unclear functions, although some are more obvious than others - Duffy antigens is the entry point for malaria, so a-b is malaria resistance. The mcleod phenotype is assoc with chronic granulomatous disease

Question 238

What are blood group antibodies?

Answer 238

Occur naturally, due to absence of exposure to corresponsing red cell antigen. They develop due to immune responses to substances in the environment with similar antigenic shapes, creating cross reactivity. These types are classically IgM Can occur following exposure to other types of blood antigens Eg. due to transfusion, transplacental haemorrhage or contaminated syringes. These are typically IgG, and can cause red cell destruction

Question 239

Differentiate between natural and immune stimulated blood group antibodies

Answer 239

Natural are glycolipid IgM antibodies that activate complement and destroy red cells intravascularly Immune mediated are glycoprotein IgG, that have only early phase complement activation and destroy red cells extravascularly.

Question 240

Describe the ABO system

Answer 240

Antigens found on red cells, platelets, granulocytes and epithelial cells Formed by addition of carbohydrates onto a base H antigen Can be OO (express anti A and B antibody) AA or AO (express anti B antibody) BB or BO (express anti A antibody AB (no antibodies)

Question 241

What is the clinical relevance of ABO blood groupings?

Answer 241

Don't normally appear in infants until 3-6 months Transfusion of incompatible cells leads to intravascular haemolysis, DIC and renal failure. Normally need same blood type to be matched for transfer, but blood group O can be transfused to anyone, while AB can receive anything. (Note this doesn't account for plasma as it is normally already removed from the red cell units).

Question 242

Describe the Rh blood grouping system

Answer 242

Restricted to red cells only. Individuals can be RhD positive or negative. Negative doesn't have the antibody. Positive being transfused to negative likely results in an anti D formation, which is unable to bind complement leading to extravascular destruction. The three gene sets that determine it are C, D and E. They are inherited together

Question 243

What is the relevance of Rh blood grouping?

Answer 243

Positive cells should never be transfused to negative women of childdbearing age due to risk of anti d formation, causing haemolytic disease of the newborn

Question 244

How do we detect red cell antibodies in the lab?

Answer 244

Use an agglutination technique. Red cells are incubated with serum. If the serum contains an antibody targeted against an antigen on the cell surface, it will clump. Serum ma be from a known antibody from a patient etc Red cells may have known antigens, obtained from donation or patient IgM leads to direct agglutination as it is large and a pentamer IgG is a dimer, so will sensitise cells to clump when anti human globulin is added (antibodies to IgG and C3)

Question 245

What is haemolytic disease of the newborn?

Answer 245

Red cell antibodies formed in the mother cross the placenta, resulting in fetal red cell destruction, and can result in severe anaemia and death. Most often occurs due to RhD compatibility. This happens when a first pregnancy exposes a negative mother to RhD positive cells during transplacental haemorrhage at delivery or abortion- anti d forms in her blood In subsequent pregnancy this crosses the placenta and damages fetal red cells

Question 246

How do we treat haemolytid disease of the newborn?

Answer 246

Use anti D immunoglobulin at the time of delivery for all negative women with a positive baby Treat infant with intrauterine transfusion All pregnant women have blood group determination and antibody screened Ultrasound and fetal blood sampling when a mismatch is checked

Question 247

What is ABO haemolytic disease?

Answer 247

Usually involves a group O mother and an A or B fetus/ However, this occurs less frequently due to ABO being poorly expressed in fetuses Antigens are also widely distributed in placental tissue, so any antibody attaches there instead

Question 248

What are other causes of haemolytic disease?

Answer 248

Anti c | Anti Kell

Question 249

How does red cell destruction harm the fetus in haemolytic disease?

Answer 249

Destruction increases bilirubin, which in fetuses can cross the BBB and cause inflammation and kerticterus (brain damage)

Question 250

What is important for a safe blood supply?

Answer 250

Use of voluntary and non remunerated blood donors Exclusion of donors whose behaviour or lifestyle increases their risk of blood borne viral infections Testing of all donated blood for blood borne viruses Use of physical and chemical methods to destroy any potential pathogens

Question 251

Why are voluntary non remunerated donors important?

Answer 251

Payment increases the likelihood that the donor will keep secret a behaviour or illness that would normally exclude, them, resulting in higher viral markers. Also, blood may be collected in the window period, where positive tests have not yet developed, and can cause transmission to the recipient even with a negative screening test

Question 252

What features are needed for a patient to donate blood?

Answer 252

Good general health 16-70yo Able to donate every 12 weeks Must complete questionnaire to protect recipient from medical and lifestyle risk factors, as well as protecting donor by identifying issues

Question 253

What is donated blood tested for and what happens if a test is positive?

Answer 253

``` ABO, RhD and antibody screen Hep B and C HIV I and 2 HTLV (human t cell lymphoblastic virus) syphillis If test is positive, the are permanently deferred, contacted and counselled. Hep B has the longest window period Remember that informed consent is needed for donation and transfusion ```

Question 254

What are blood products available in nz?

Answer 254

- Blood components- single donation or small pool of donors. All are leukodepleted prior to transfusion via filtration. Red cells are given for improvement of oxygen delivery in case of anaemia or blood loss Platelet concentrates are given to avoid bleeding in thrombopenic patients Fresh frozen plasma is for correction of abnormal coagulation in bleeding patients- immediate warfarin reversal, coagulation deficiency or DIC- NOT as volume expander or immunodeficiency correction

Question 255

How do the ABO reactions for plasma transfusion compare to RBC transfusion?

Answer 255

They are the opposite as it is the antibodies being transfused, not the antigens O is universal receiver, as they can have any group due to lack of self antigens AB can only have AB

Question 256

What is plasma derivative?

Answer 256

Manufacturesd from a pool of plasma, where blood is centrifuged, plasma is removed, and a preservative is added Can be transfused after a viral inactivation process

Question 257

What are some issues with blood transfusion?

Answer 257

Overuse Stored blood can cause adverse outcomes Also need to account for patient cariopulmonary reserve, volume of blood loss, O2 consumption and possible atherosclerotic disease

Question 258

What is the checklist used before prescribing transfusion?

Answer 258

``` What improvement do I am for Can I minimise loss before transfusing Any other treatments first? Specific indication? Benefit > risk? ```

Question 259

What are the five classes of Ig?

Answer 259

``` IgA IgD IgE IgG IgM ```

Question 260

Describe IgM

Answer 260

Large pentamer confined to the bloodstream. Made by new B cells Produced early in the primary antibody responses with good defence against bacterial spread Good agglutinator and complement activator

Question 261

Describe IgG

Answer 261

``` Small monomer diffusing easily out of the bloodstream. Made by memory cells. Major secondary response class Good complement activator, opsonin and Fc receptor mediated effector (good against viruses and toxins) ```

Question 262

Describe IgA

Answer 262

Predominant in seromucus secretions, like in airwas, gut and GU Defence of exterior surface

Question 263

Describe IgD

Answer 263

Highly sensitive to proteolysis | Received by virgin, antigen-sensitive B cells

Question 264

Describe IgE

Answer 264

Trace amounts elevated in parasite infections | High affinity Fc receptor on mast cells and basophils, so involved in allergy symptoms

Question 265

Give an overview of the general structure of antibodies

Answer 265

Made up of four polypeptide chains held together with disulfide bonds Light chains can be kappa or lambda Heavy chains can be gamma, mu, alpha, epsilon or delta (which determines the antibody class) They also have an Fc region, for which many cells have high affinity receptors (esp neutrophils) Each arm has two identical binding sites

Question 266

What can be indicated by lower than normal numbers of IgG, M and A (most common classes) ?

Answer 266

Suggests that antibodies are not being properly made With few B cells could be agammaglobulinaemia As we develop maternal IgG is given to us, which lasts several months after birth, so symptoms show up after birth. Our own IgG should rise along with IgM- IgA is produced more slowly Treated with widespread antibodies periodically Can also give bone marrow transplant (though issues with compatability)

Question 267

What is the process of triggering antibody production?

Answer 267

Surface Ig allows B cells to bind and internalise antigens This is processed and fragments are expressed by MHC II, to be presented to Th cells. CD40 and CD40L bind, allowing the B cell to differentiate into antibody forming plasma cells

Question 268

What is antibody class switching?

Answer 268

IM is the first class synthesised in a primary antibody response, but eventually declines t be replaced by IgG. The B cells switch from IgM to IgG. This is because T cels cause the removal of heavy chain components to bring the VJD region next to the gamma region of the heavy chain

Question 269

Describe how antibodies perform direct neutralisation

Answer 269

They can physically prevent adsorption to target cells, and inhibit the attachment of bacterial and plant toxins to cells They are also able to immobilise bacterial flagella

Question 270

Describe how antibodies perform agglutination

Answer 270

Antibodies like IgM have several binding sites that clump together multiple small particles for better phagocytosis

Question 271

Describe how antibodies perform opsonisation

Answer 271

Granulocytes and macrophages have surface Fc and C3b receptors. This means phagocytes can recognize and bind to antigen-antibody complexes with high affinity to increase their efficiency

Question 272

Describe antibody dependent cell mediated toxicity

Answer 272

Some K cells have Fc and C3b receptors, where they bind to the antibody-antigen complex and deliver short range cytotoxicity factors

Question 273

What is the complement system?

Answer 273

Can be activated by antigen-antibody complexes or by components of some bacterial cell walls and yeasts It results in a cascade of proteolytic enzymes which cleave other complement proteins into active forms, eventually resulting in the formation of the membrane attack complex

Question 274

Give the steps of the complement cascade

Answer 274

C3 is cleaved into C3a and C3b. C3a is an anaphylatoxin, which stimulates histamine, causing vascular permeability and vasodilation, as well as functioning as a chemotactic factor C3b Binds to other molecules or and cells nearby, with a short half life. It is recognised by receptors on phagocytic cells, resulting in enhanced phagocytosis. It also forms a focus for assembly of late complement components C5,6,7,8,9 also assemble to form the membrane attack complex and producing increased chemotactic factors

Question 275

Describe the alternative pathway in complement activation

Answer 275

Most important in the early stage of bacterial or yeast infetion Alternative C3 cleaving enzyme is Mg2+ dependent complex of C3b and Factor B, activated by Factor D. Initiated by trace amounts of C3b formed by small amounts of spontaneous C3 breakdown

Question 276

What is the difference between polyclonal and monoclonal antibodies?

Answer 276

Antibodies produced by B cells are polyclonal as several clones of B cells are activated to produce the repertoire of antibodies for a particular epitope Lab techniques have developed monolonal antibodies, where single antibody-forming cells can indefinitely produce them. These are used for diagnostic reagents and therapy

Question 277

How has a monoclonal antibody been used clinically?

Answer 277

Treatment of B- cell chronic lymphoid leukaemia, showing increased B cells, lymphadenopathy, splenomegaly, leukocytosis, and smear cells Treated with rituximab, which allows complement, opsoniation and NK cells- more effective than chemo as they target only the specific cancerous cells

Question 278

What are the steps involved in pretransfusion testing?

Answer 278

Correctly identify the patient with blood sampling and labelling at the bedside. Need name and DOB, confirmed with label Determine ABO and Rh type Antibody screen for irregular cell antibodies Select approproiate red cells and remove from fridge Final identity check and cross match

Question 279

What can go wrong with blood transfusion?

Answer 279

``` Wrong patient label on the sample Lab procedural mistake Blood issuing or storage error Wrong blood given to patient (mostly human error) ```

Question 280

What is an antibody screen and why is it important?

Answer 280

It aims to identify the presence of the msot important red cell antigens on the surface of red cells. The RBCs are incubated with IgG, washed, and tested with AHG. If present, the cells will agglutinate

Question 281

How are red cell units selected in normal and emergency situations?

Answer 281

Emergency- desperate need uses o neg when group is unknown. There can also be group-compatible or fully compatible blood used when there is time Normally- group and scan used before surgery, with antibody screening hopefully negative. If the antibody screening test is positive, we can do an immediate spin test to determine ABO incompatability, or computer crossmatching for a final ABO check

Question 282

What needs to be done if a transfusion reaction occurs?

Answer 282

Stop the transfusion, maintain the line with saline and seek advice

Question 283

What are the different complications of transfusion possible?

Answer 283

Immunological- Early reactions can be haemolytic, febrile non haemolytic, acute lung injury (TRALI) or reactions to proteins. Late reactions can be delayed haemolytic, post transfusion purpura or graft vs. host disease Non immunological can be bacterial or viral transmission

Question 284

What are the possible causes of acute transfusion reactions?

Answer 284

``` Bacterial sepsis Immediate haemolytic transfusion reaction Anaphylaxis Circulatory overload Febrile non haemolytic ```

Question 285

Describe bacterial sepsis and how it can be caused by transfusion

Answer 285

Rare but serious, assoc with contamination of blood with endotoxin-producing bacteria Presents as sudden hypotensive shock

Question 286

Describe how transfusion can cause an immediate intravascular haemolytic reaction

Answer 286

Rare but very serious. Usually due to ABO incomatability Complications include renal failure and DIC This is because the antibody-antigen complexes formed trigger complement, leading to haemolysis Symptoms are fever, restlessness, retrosternal or loin pain, increased temp, hypotension and uncontrolled bleeding

Question 287

Describe how transfusion can cause extravascular haemolytic reactions

Answer 287

Due to presence of IgG antibody in patient plasma, with no complement activation past the early phase. However, the complex does cause them to be digested by macrophages etc.

Question 288

Describe delayed haemolytic transfusion reaction

Answer 288

Due to memory immune response, occurring several days post transfusion Hb decrease with jaundice. The system has been sensitised by previous transfusion or pregnancy, but the antibody is too low to be detectable during screening

Question 289

Describe febrile non haemolytic transfusion reactions

Answer 289

Common, mostly in platelet transfusion. Fever starting during transfusion, assoc with rigors. Due to presence of antibodies within recipient serum, cytokines and other modifiers that accumulate with storage Need to investigate, exclude sepsis, give paracetomol and possibly antihistamine

Question 290

What is TRALI?

Answer 290

Transfusion related acute lung injury Onset of injury within 6 hours, as plasma containing white cell antibodies leads to agglutination of recipient neutrophils in pulmonary vasculature, as 3/4 of these are in the lungs.

Question 291

What is transfusion assoc circulatory overload?

Answer 291

Underlying cardiovascular function is low enough to risk volume overload Those at risk are those with compromised CV function, renal failure, CHF, high transfusion volumes, and the elderly Treat with diuretics

Question 292

Describe the allergic reactions that can happen in transfusion

Answer 292

Reactions to plasma proteins - Anaphylaxis is rare and early onset, with hypotension, dyspnoea and abdominal cramps- classically in an IgA deficient person with antibodies Urticarial- common reactions, should slow transfusion and give antihistamine. Specific to individual donation, so low recurrence risk

Question 293

How are HLA genes important in grafts?

Answer 293

A non matched graft will cause graft rejection due to CD8 cell activation. Memory cells are generated so that repeat grafts are rejected more quickly

Question 294

How are CD8 T cells activated?

Answer 294

Foreign antigen comes into contact with T cells/ Those with receptors that bind most strongly are selected and activated to respond Further signals are provided by TH cells, causing the cytotoxic cells to proliferate and differentiate into cytotoxic effector cells, which proceed to seek out and destroy matching cells This is due to cross-priming, where dendritic cells can be licenced to present their antigens to CD8 T cells, allowing both TH and TCT cells to be activated

Question 295

What mechanisms do CD8 cells use to kill other cells?

Answer 295

- Insert a complex called perforin into the membrane, which cause donut shaped holes to form - Release enzymes that digest the target cell membrane Release cytokines that bind to receptors on target cells to induce apoptosis

Question 296

What is the sequence of gene rearrangement in the development of B cells?

Answer 296

There are three sets of Ig genes- a heavy chain, k light chain and l light chain. 1. Heavy cell VDJ exons produce cytoplasmic M heavy chains, causing surface IgM expression Light chains initially try k and then l if k rearrangements fail IgM is tested for self-reactivity in the bone marrow If no self recognition then they reconstruct to IgD by removing the M component, and export to secondary organs The VDJ region is attached to the constant zone, which has the different Ig proteins on it. Class switching edits this region

Question 297

Describe central tolerance of B cells

Answer 297

As some receptors may recognise self antigens, receptors on immature B cells are tested for binding to common self antigens Those with IgM that respond to self antigens are deleted. This gives us immune tolerance to self antigens

Question 298

Describe the appearance of the thymus and what it means in terms of T cell development

Answer 298

The cortex appears darker than the medulla. The medulla expands as we age, as the acellular areas develop more as we get older. Differentiation starts in the cortex and moves into the medulla as T cells become more specific. Only T cells with appropriate receptors are allowed to fully mature

Question 299

What are the different loci for TCR polypeptides and what do they do?

Answer 299

there is alpha, beta, gamma and delta TCRgd are uncommon, found largely in the mucosa of the gut and skin, likely functioning as head shock proteins expressed in response to stress

Question 300

How are maturing T cells selected for and against?

Answer 300

Each thymocyte rearranges it ITCab or TCRgd genes in the thymus. Cortical thymocytes express both CD4 and CD8 accessory molecules, and they develop from being 'double positive' to 'single positive'. They must express TCR that recognize self MHC with low affinity so that they can recognize it with higher affinity when it is assoc with foreign epitopes. (positive selection) It must also not regognize it so strongly that it undergoes self reaction. (negative selection Our HLA determines our receptors and antibodies. There are conditions where we can have 'gaps' in our repertoires.

Question 301

What are the features of endocarditis?

Answer 301

Symptoms and signs of infection Embolic phenomena Abnormal heart valve

Question 302

What are some examples of embolic phenomena

Answer 302

Splinter haemorrhange- linear blood lines under the neail due to small emboli Also shows in hands, feet and lower lid Small clots block these vessels and cause them to leak

Question 303

Describe the changes to the heart valve and how this can cause embolic phenomena in endocarditis

Answer 303

Vegetations grow on the edges of the valve, and can perforate it. These have bits that can break off, and altered blood flow also increases risk of clots to the brain, kidneys and spleen, as well as causing inflammatory symptoms

Question 304

What is the pathogenesis of endocarditis

Answer 304

1. Turbulent flow through an abnormal due to congenital defects, RH nodules etc 2. Platelets and fibrin attach, forming sterile vegetations 3. Transient bacteraemia from the mouth, skin, gut, urinary tract etc. seed bacteria onto the sterile vegetations 4. Infected vegetation enlarges and sheds infected emboli, leading to valvular destruction and leakage

Question 305

What are the causes and consequences of endocarditis?

Answer 305

Caused by strep viridans, staph aureus or enterococcus faecalis Causes impaired valve function and heart failure as the ventricles dilate to accommodate the increased blood, as well as the formation of emboli causing infarcts There is 0% chance of host cure as neutrophils can't attach to the valves due to the speed of the blood

Question 306

How do we diagnose endocarditis?

Answer 306

Diagnose continuous bacteraemia, with all blood cultures over time positive with an endocarditis-causing bacteria. (at least 3 at least 20 mins apart) Perform an echo Look for evidence of emboli

Question 307

Differentiate true, contaminant and transient bacteraemia

Answer 307

True bacteraemia is when the pathogen is cultured with a clinically compatible infective source more than once Contaminant bacteraemia is when a skin commensal is cultured, and only one set is positive Transient bacteraemia is where gut or mouth bacteria is cultured, not an infective source, and the positive result only occurs briefly

Question 308

How do we treat endocarditis?

Answer 308

Antibiotics via IV, high dose, for at least 2 weeks. The one used depends on the cause of the infection Some are more sensitive or less sensitive, and the antibiotic must be bactericidal rather than bacteriastatic. Duration depends on speed of bacterial killing Generally we give the highest dose tolerable via IV (3mU 6hrly for 28 days) Sometimes synergy can be useful (eg. penicillin with gentamicin)

Question 309

How do we prevent development of endocarditis in those with abnormal heart valves?

Answer 309

Prophylactic antibiotics (eg when doing dental work)- usually only one dose of penicillin

Question 310

Differentiate between endocarditis and RHD

Answer 310

Rheumatic fever can only be caused by strep pyogenes, involves pharyngitis, and immunologic damage to valves Valves present with nodules. Treated with oral penicillin for 10 days, and intramuscular penicillin prophylactically for 10 years after Endocarditis is caused by strep viridans mainly, as well as other, including mouth commensals It involves infection of valves which show vegetations It is treated with a month of IV penicillin, and prophylaxis with oral penicillin during procedures such as dental work

Question 311

What are the symptoms of acute gastrointestinal illness?

Answer 311

Vomiting Diarrhoea, including acute watery, bloody, or severe (6+ per day) Abdominal pain/cramping Fever

Question 312

What can cause acute gastrointestinal illness?

Answer 312

Bacteria- colonise intestine and produce toxins, invade tissue, or the toxin itself is what is ingested Viruses Protozoa

Question 313

Describe the ways in which viruses cause gastrointestinal illness

Answer 313

They colonise the small intestine and generally produce forty eight hour, self limiting illness Can be due to norovirus, rotavirus (stimulates Cl- secretion into the gut) Treated with supportive treatment, and rehydration

Question 314

Describe the ways in which bacteria can cause gastrointestinal illness

Answer 314

- Colonisation of intestines and producing toxins- including clostridium dificile, shiga toxin producing E coli (STEC), shigella dyenteriae, E coli and vibrio cholerae- dysentery is common - Colonisation of intestines and invasion of tissue (yersinia, non typhoid salmonella) - Toxin produced in food and ingested with no infection. Result is food poisoning - Eg. staph aureus. Causes vomiting within 2-7hrs, with symptoms clearing in 1-2 days

Question 315

Describe the ways in which protozoa can cause acute gastrointestinal illness

Answer 315

Can colonise the small intestine- eg. giardia, cryptosporidium Mainly passed on by food and water contaminated by feces Incubation of 1 or more weeks with symptoms lasting 4-6 weeks Produces diarrhoea, flatulence, cramps Antimicrobials may be necessary cysts are reistant to disinfectants

Question 316

Describe how gastrointestinal illness is different between bacteria, viral and protozoal causes

Answer 316

Virus has an onset of hours/days while protozoa takes days/weeks Bacteria and protozoa have diarrhoea, where viruses may Viruses have vomiting, whereas bacteria and protozoa may Viruses show fever while bacteria and protozoa show more abdominal pain

Question 317

What is an outbreak?

Answer 317

2 or more cases linked to a common cause

Question 318

What are the sources of gastrointestinal illness transmission and what is being done to prevent this?

Answer 318

Animal or human fecal oral, either direct or indirect Animals Infected people and carriers Contaminated food or water Prevented by proper slaughtering and farming practices, food cooking and storage, and good hygeine

Question 319

What are risk factors for gastrointestinal illness?

Answer 319

Consuming food from retail premises At risk food Contact with farm animals, untreated water, faecal matter, symptomatic people, recreational water, travelling in the incubation period and contact with sick animals

Question 320

What are some diagnostic tests for gastrointestinal illness?

Answer 320

MacConkey lactose- differentiates E coli from salmonella, shigella and yersinia MacConkey sorbitol- differentiates STEC from E coli XLD differentiates salmonella and shigella from others Can also do antibodies and PCR for toxins

Question 321

What are complications of gastrointestinal illness?

Answer 321

``` Dehydration Bacteraemia Haemolytic uremic syndrome Guillain barre syndrome- cross reaction with AI attack of motor neurone sheath, causing (possibly temporary) paralysis Reactive (autoimmune arthritis) ```

Question 322

How do you treat GI illness?

Answer 322

Symptoms treated with fluid and electrolyte replacement, easily digestible foods, antimotility drugs for watery diarrheoa (but not other types as it concentrates the toxins) Antibiotics usually not required, esp for STEC as it increases toxin production. Only needed in C difficile and salmonella/campylobacter if patient is at risk

Question 323

How can GI illness be prevented?

Answer 323

Vaccines- limited | Sanitation, hygiene, effective cooking, food safety and avoidance of risk food is best option

Question 324

What is a fever?

Answer 324

A state of elevated core temperature in response to invasion of live or inactive matter recognized as pathogenic or alien by the host

Question 325

What is the key immune component responsible for fever?

Answer 325

IL-6, which is released by macrophages and the innate immune system. It causes the anterior pituitary to produce pyogens and then cryogens to help time the febrile response

Question 326

Why is fever useful?

Answer 326

It helps prevent replication of some pathogen Helps to enhance the immune response, esp for neutrophils Also causes sickness behaviour

Question 327

When should you investigate a fever?

Answer 327

If it has had a long duration, occurs in an immunocompromised individual, occurs in an unwell person, or if the patient is less than 12 months old

Question 328

Should we treat fevers in an otherwise well child?

Answer 328

Fevers under 41 degrees aren't dangerous by themselves Can show benign febrile convulsions- reducing the fever doesn't prevent this Mainly treated to make people feel better However, patients in the ICU with brain injury need fevers to be prevented

Question 329

What is the pathogenesis of meningitis?

Answer 329

The CSF contains bacteria, white blood cells, inflam proteins and cell debris Inflammation of the subarachnoid space leads to inflammation on the brain surface itself

Question 330

What can cause meningitis?

Answer 330

Viruses- a common, mild form Fungi- rare, due to AIDS or cancer Protozoa- rare, due to accidental ingestion Bacteria- common, and a serious medical emergency. Most likely due to N meningitidis, or strep pneumoniae

Question 331

What are the symptoms of meningitis?

Answer 331

``` Fever Drowsiness Photophobia Neck stiffness Headache ```

Question 332

Describe bacterial meningitis

Answer 332

Illness is preceded by nasopharyngeal colonisation, followed by bacteria entering the subarachnoid space and propagating

Question 333

How can meningitis be diagnosed?

Answer 333

Kernig's sign- when lifting the legs upwards, meningitis will show pain first in the head and neck as the meninges are stretched, rather than in in the hamstrings CSF sample, blood cultures, throat swab, or blood PCR for viral causes- often needed when meningitis doesn't present with a rash

Question 334

Describe the difference in CSF samples between bacterial and viral meningitis

Answer 334

Bacterial will have lower glucose, predominantly neutrophils instead of lymphocytes and may be positive gram or culture Both will have increased protein and WBCs

Question 335

How does meningicocal avoid the immune system?

Answer 335

It has a single layer of peptidoglycan cell wall but avoids the complement system by turning it off via factor H It also cleaves C3 convertase and produces huge amount of lipopolysaccharides to 'distract' the immune system In response to this, the neutrophils die and release DNA, forming sticky nets in the capillaries. This traps bacteria but leads to clotting and clogging, reducing organ perfusion, leading to shock

Question 336

What are the symptoms of shock?

Answer 336

``` Fever Bradycardia Low blood pressure Drowsiness Confusion and agitation Tachypnoea Oligouria Aches and pains Gray, clammy skin ```

Question 337

How is bacterial meningitis treated?

Answer 337

``` IV antibiotics Recuscitation Blood cultures Hospitalization Pain relief, fluids, droplet precautions Prophylaxis is given to contacts ```

Question 338

What are the medications used to treat meningitis?

Answer 338

Cephalosporins (ceftriaxone) or penicillins | Cephalosporins have a similar structure to penicillin but can be used in most penicillin-allergy patients

Question 339

What are the different cephalosporins used for?

Answer 339

Skin infection, pneumonia, UTI and GIT infections | Ceftaroline has activity against MRSaA

Question 340

How do you manage septic shock?

Answer 340

Maintain organ function using IV fluids and oxygen | Resolve the cause of the infection using antibiotics and surgery

Question 341

What is urethritis?

Answer 341

A condition occurring in symptomatic males with lots of polymorphic nuclear leukocytes. The symptoms are of an anterior urethritis, with discharge from littre's glands (pus and mucus) and dysuria.

Question 342

What are some causes of vaginal discharge?

Answer 342

Normal- cyclical variation or cervical mucus Cervicitis creates a purulent discharge due to endocervical infection, and also shows strawberry cervic Genital candidiasis and bacterial vaginosis also shows abnormal discharge

Question 343

Describe chlamydia

Answer 343

Commonly asymptomatic, mainly affects the serially monogamous Due to an intracellular bacteria that takes over the energy machinery of the cell, producing reticulate and alimentary bodies until the cells burst, causing inflammation, discharge and further infection

Question 344

What are the symptoms of chlamydia?

Answer 344

Male: Urethritis, epididimytis. proctitis, reiter's syndrome, conjunctivitis Female: Cervicitis, sterily pyuria, PID, perihepatitis, infertility, conjunctivitis Neonate: Conjunctivitis, pneumonia, otitis media

Question 345

How does chlamydia progress and how is it diagnosed?

Answer 345

Initial infection is mild, and short term immunity develops. Recurrent infections causes severe inflammation due to exaggerated host response, potentially causing an AI response due to a cross reacting heat shock protein. Diagnosed with nuclear acid amplification tests (NAAT) including PCR Specimens can be collected from urine in asymptomatic and symptomatic men, as well as a vulvovaginal swab for women

Question 346

How is chlamydia treated?

Answer 346

``` Typically doxycycline, but with pregnant/breastfeeding women we use azithromycin- but this has some side effects like GI, LQTS exacerbation & resistance Partner notification (all in last 60-90 days) and treatment ```

Question 347

What are some possible complications of chlamydia?

Answer 347

Men- epididymitis and infertility | Reiter's syndrome- sexually acquired arthritis

Question 348

Describe gonorrhoea

Answer 348

Caused by a gram negative diplococcus Infects non cornified epithelial cells Has several defence mechanism including pilin for adherence and neutrophil resistance

Question 349

How do you collect and diagnose gonnorrhoea?

Answer 349

Always taken from the site with symptoms Grown in a selective artificial medium- NYC medium for genital site, thayer martin for anal Representative colonies are oxidase positive An E test strip shows antibodies at different gradiations along a plate, allowing the amount of gonorrhea to be determined NAAT may also be used

Question 350

What are the symptoms of gonorrhea?

Answer 350

Most are symptomatic, with anterior urethritis and meatitis. It normally goes away in 6 months if untreated Women- coital bleeding, intermenstrual bleeding, discharge, dysuria etc Can also have symptomatic or asymptomatic rectal transmission (more common in women) or pharyngeal infection from oral sex

Question 351

How is gonorrhea treated?

Answer 351

If uncomplicated and sensitivity unknown, treated with ceftriaxone If known sensitive, treated with ciprofloxacin Concurrent antichlamydial treatment Also treat partners from last 30-90 days

Question 352

What are some complications of gonorrhea?

Answer 352

Males- Epididymitis- unilateral testicular pain and swelling Lymphangitis Rarely urethral stricture Females- PID

Question 353

Describe PID

Answer 353

Pelvic inflammatory disease Mild may have secondary dysmenorrhoea, intermenstrual or postcoital bleeding, vaginal discharge, cervical motion tenderness, uterine tendeness Moderate/severe is often due to mixed microbial infection can have perihepatic pain due to adhesions forming between the liver and diaphragm Treated with activity against gonococcus, chlamydia and anaerobes

Question 354

What are complications of PID?

Answer 354

Chronic pain Infertility Ectopic PID

Question 355

What is DGI?

Answer 355

Disseminated gonococci infection, occurring in up to 3% of cases Most commonly presents with dermatitis arthritis syndrome. Can occur in males but commonly in postmenstrual females, with complement deficiency

Question 356

What is non specific urethritis and what can cause it?

Answer 356

Urethritis not caused by chlamydia or gonorrhea Often caused by trichomonas vaginalis in women- only transiently symptomatic in men Also mycoplasma genitalium, adenovirus

Question 357

Describe trichomoniasis

Answer 357

Caused by a flagellated protozoan Diagnosed on wet film, culture, PCR. Difficult to detect in men (who are usually asymptomatic anyway) Sexually transmitted disease causing vaginitis, adverse pregnancy outcomes and transient vaginitis in the neonate

Question 358

What can cause lymphadenopathy?

Answer 358

Proliferation of lymphocytes in response to local infection Proliferation of metastasised malignant cells Proliferation of malignant lymphocytes Inflammation in nodes from killing of lymphocytes with a virus

Question 359

How do you investigate lymphadenopathy?

Answer 359

Look for adjacent infection/cancer Fine needle aspiration/excision to look at cell features Look at evidence of infection targeting lymphoid cells

Question 360

What can infect lymph nodes?

Answer 360

Bacteria: Staph aureaus, tuberculosis Viral: EBV, CMV, HIV

Question 361

Describe how the herpes viruses can affect the lymph nodes

Answer 361

They are DNA viruses that cause asymptomatic latent infection followed by reactivation Acute EBV for example shows a minor illness in childhood and severe when adolescent or older Transmitted by saliva will 1-2 week illness with fever, sore throat, cervical adenopathy, malaise and fatigue Shows increased lymphocytes, abnormal lymphocytes, EBV antibodies and antigens

Question 362

Describe the early symptoms of HIV

Answer 362

Recent exposure Glandular fever like illness Persistent viraemia and virus in genital secretions Antibodies to HIV in the blood

Question 363

How does HIV replicate?

Answer 363

GP120 binds to CD4 and its co receptor on the T cell Viral envelope fuses with host cell cytoplasmic membrane, Viral DNA copied into T cell DNA by reverse transcriptase HIV DNA taken into cell nucleus, cut and integrated, cuasing viral proteins to be synthesised GP41 and 120 are inserted into host cell membrane Proteins and viral RNA are assembled HIV cell buds off and goes on to infect more cells

Question 364

What is the course of HIV infection?

Answer 364

``` Infection Level of virus rises in blood T cells kill HIV infected T cells T cells fall HIV falls Glandular fever like illness B lymphocytes produce HIV antibodies Level of HIV stable for years T lymphocytes continue to fall T cell depletion severe AIDS HIV rises ```

Question 365

How do you test for HIV?

Answer 365

ELISA HIV antigen stuck in tube, with serum sample added Anti-human antigen added- attaches to serum antibody if present Reagent added- it is cleaved by an enzyme on the anti human antibody causing a color change More HIV will cause more of a change Light change can be due to EBV, CMV, HPV

Question 366

What are the different types of hypersensitivity reactions?

Answer 366

Type 1: IgE mediated allergy/atopy/anaphylaxis Type 2: IgG antibody mediated CT reactions Type 3: IgG immune complex mediated reactions (These two are the main autoimmune classes- Type 2 is organ specific and type 3 is systemic) Type 4: T cell mediated delayed immune reactions

Question 367

Describe type 1 hypersensitivity

Answer 367

Occurs when an allergen cross links two IgE molecules by their Fc receptors. This causes mast cell activations and degranulation, releasing histamine, chemotactic factors, heparin etc. Most sufferers have high IgE concs

Question 368

What are the different types of Type I hypersensitivity reactions?

Answer 368

Respiratory tract: Allergic rhinitis, sinusitis, asthma Eyes: Conjunctivitis Skin: Urticaria, angioedema Gut: Diarrhoea, cramps, vomiting Multiple organs: Anaphylaxis Generalised and severe asthmatic reactions can be fatal Bronchial reactions show immediate IgE and late IgG

Question 369

Describe type 2 hypersensitivity reactions

Answer 369

Antibodies bind to cell surface antigens and activate NK cells Due to complement fixation (Haemolytic disease of newborn) Followed by: ADCC- cells have receptors for the FC protion of Ig molecules

Question 370

How are type 1 hypersensitivity reactions treated?

Answer 370

``` Avoidance Antihistamines for mild forms Corticosteroids for chronic Na cromoglycotics to stabilize mast cells Adrenaline for anaphylaxis Desensitisation ```

Question 371

Describe type 3 hypersensitivity reactions

Answer 371

Antibodies and complementary antigens are high at the same time, allowing lots of binding and complement activation. Other immune cells are recruited The complexes deposit in the skin, causing rash, joints causing arthritis and the kidney causing nephritis It causes vascular damage Mechanism for SLE

Question 372

Describe Type 4 hypersensitivity reactions

Answer 372

Initial phase involves uptake, processing ant antigen presentation to T cells. This then produces cytokines, macrophages, etc. Upregulates adhesion molecules and MHC receptors Small molecules bind to normal proteins, modifying their shape and allowing their transport too. Eg. Mantoux reaction- protein derivative of tuberculin injected to test for mycobacterium exposure. Mechanism for contact sensitivity

Question 373

How do immune cells develop tolerance?

Answer 373

Clonal deletion- self reacting cells are tested and deleted while developing in the primary lymphoid organs Clonal anergy- self reacting lymphocytes still exist, but are resistant to stimulation- important for peripheral antigens Suppression- Self reactive lymphocytes are kept in check by Treg cells Immunological ignorance- Self reactive cells are there, but their antigens are in immune privileged sites or there is inadequate T cells help

Question 374

Describe autoantibodies

Answer 374

Usually IgM, low titre and low affinity, or directed against sequestered antigens Normally have a regulatory role to dispose of breakdown products. Autoimmunity is common, autoimmune disease is rare Antinuclear antibodies are high in old age and SLE. Antithyroid antibodies are common in thyroid disease and the elderly

Question 375

Describe cross reactions in immunity

Answer 375

Antibodies against viral RNA or DNA may cross react with self RNA or DNA Infection with some bacteria can result in reactive arthritis, endocarditis etc due to antigens cross reacting will cell surface antigens due to molecular mimicry

Question 376

What are some examples of autoimmune disease?

Answer 376

``` Thyrotoxicosis caused by TSH antibodies Pernicious anaemia Idiopathic thrombocytopenic purpura Addison's disease Myaesthenia grapvis Goodpastures syndrome Idiopathic diabetes melitus ```

Question 377

What can predispose a person to autoimmune disease

Answer 377

Ig genes TCR genes Complement (eg. SLE is due to deficient complement components, resulting in reduced complex clearance) MHC genes and types

Question 378

How are autoimmune diseases treated/

Answer 378

Replacement of factors lost through the disease- eg. insulin, thyroxin, glucocorticoids and mineralocorticoids Suppression with immunosuppression SLE- uses corticosteroids, azathioprine, cyclophsphamide RA: Suppressed with corticosteroids, NSAIDS

Question 379

What are the categories of immune mediated skin disease?

Answer 379

Some is caused by autoimmunity Some is caused by impaired skin barrier function Some is caused by immunosuppression

Question 380

What are three immune skin diseases assoc with autoimmunity?

Answer 380

Urticaria Bullous pemphigoid Pemphigus Vulgaris

Question 381

Deescribe urticaria

Answer 381

Commonly known as wheals. Angioedema is the deep form of this. Causes include physical, infectious immune related and sometimes due to classical autoimmunity

Question 382

Describe bullous pemphigoid

Answer 382

Usually presents in older patients with an itchy rash and then development of blisters Due to an autoimmune IgG reaction against proteins in the hemidesmosomes that stick the epidermis to the dermis. This causes the epidermis to loosen and split. Neural tissue has a similar antigenic shape to the hemidesmosome proteins and so neural damage can cause cross reactivity between these proteins

Question 383

Describe pemphigus vulgaris

Answer 383

Can involve the mucous membranes as well as the skin An AI reaction against proteins in the desmosomes that help keratinocytes to stick to each other within the layer of the epidermis. This produces shallow blisters and skin erosion

Question 384

How are bullous pemphigoid and pemphigus vulgaris distinguished?

Answer 384

Direct immunofluorescence. Fluorescent anti human antibodies are directed against the antibodies causing BP and PV, so in pemphigoid is shows fluorescence at the basment membrane, while pemphigus shows it in the epidermis itself

Question 385

Describe eczema

Answer 385

This is a disease of impaired skin barrier function, with some having a mtation in filaggrin, normally a natural moisturiser. This means that antigens can penetrate more easily, leading to immune reactions. Occupations such as hairdressing can predispose to a higher risk of allergic contact. Those with a background of atopic eczema are at high chance of allergic contact dermatitis in these professions Irritant contact dermatitis is due to wear and tear on the hands, and is not allergenic Patch testing is used to determine which antigens are important

Question 386

Describe how immunosuppression can cause skin disease

Answer 386

Can be immunosuppressants due to treatment of disease, an immunodeficient disease, or immunosuppression for organ transplatation Can cause either infection (treat clinically, then blood test, swab, culture) or neoplasia- those immunosuppressed are at increased risk of skin cancer as the normal immunological surveillance mechanisms are suppressed

Question 387

What is peritonitis and what are the different types of it?

Answer 387

Peritonitis in inflammation of the peritoneum in the abdominal cavity, which may be diffuse or localised/abscess It can be primary (spontaneous) due to infection without loss of GI integrity- assoc with liver disease It can be secondary, resulting from loss of GI integrity or infected viscera. It is most common, resulting from visceral pathology or surgery It can be teritary, which shows recurrent infection following therapy- due to defective immunity

Question 388

What can be the causative agents of peritonitis?

Answer 388

Polymicrobial with more than one species involved Bacterialcan be enterobacteriaceae, like E coli, or anaerobes like B. Fragilis. May come from the stomach/duodenum (aerobes/facultative anaerobes), jejunum/ileum (aerobes and anaerobes) or the colon (anaerobes and facultative anaerobes)

Question 389

How is bacteria transmitted to the peritoneum?

Answer 389

Via a perforation- can be ruptured appendix, ruptured inflamed diverticulum, ulcer, inflammation or abscess of visceral organs, PID, tubo-ovarian infection, necrotising enterocolitis, surgery Risk increased by liver disease, portal hypertension, ascites, surgery, immune deficiency, appendicitis, diverticulitis etc

Question 390

What happens in the peritoneum after infection?

Answer 390

Bacteria enter and are not fully cleared, allowing proliferation, inflammation and abscess formation

Question 391

What are the symptoms of peritonitis?

Answer 391

Fever, increased HR, RR, N&V, diffuse or localised pain, rebound tenderness, rigidity, and increased blood leukocytes

Question 392

How is peritonitis diagnosed?

Answer 392

CT ultrasound for fluid accumulation, aspiration, gram staining and culturing of pus Bacteroides are often overlooked but present in mixed infection Isolation, gram staining, chromatography and PCR may be used Often polymicrobial infections involve B fragilis (antiphagocytic capsule, eliciting fibrin to form an abscess, complement degradation, reduced O2 toxicity) and E coli- Haem Binding protein may be intercepted by fragilis

Question 393

How is peritonitis treated?

Answer 393

Symptoms with pain meds, fluid, pus drainage Source treated with establishing cause, removing pus, dead tissue and surgically repairing any leaks Bacteria treated with empiric broad spectrum antibiotics Triple therapy is best, targeting enterobacteriaceae, anaerobes and enterococcus Single therapy is better for liver/kidney disease patients Treated 1-2 weeks or 4-6 weeks + until symptoms and signs resolved Danger of C difficile infection with longer regimes.

Question 394

What does HIV and AIDS stand for?

Answer 394

Human immnodeficiency virus | Acquired immune deficiency syndrome

Question 395

What are some examples of illnesses that are only found with AIDS sufferers?

Answer 395

Strong assoc with oral candidas in the early stages Karposi's sarcoma (cancer of blood vessel cells due to chronic herpes virus infection Toxoplasma gondii brain abscesses Cryptococcus neoformans meningitis is also a common fungus

Question 396

How is HIV treated?

Answer 396

Antiviral drugs

Question 397

What are the types of fungal infection?

Answer 397

Can be common, minor skin and mucosal infections May be rare, serious deep tissue infection They can be yeasts (eg. candida albicans, cryptococcus) that reproduce by budding They may be moulds (eg. dermatophytes, aspergillus)

Question 398

Describe candida albicans

Answer 398

Commensal organism in the mouth, gut and vagina. Overgrowth occurs when there is antibacterial therapy (as bacteria keep it in check), immune suppression, hormones or foreign bodies. It can cause oral or vaginal thrush, cutaneous or nail candidasis, cathether related bladder infection, and sometimes systemic infection Intertigo is a form that occurs in damp damaged skin

Question 399

How is candida diagnosed and treated?

Answer 399

Shows as black yeasts with pseudo-hypae (longer cells) on gram stain of a blood agar Treated with topical pastilles or cream

Question 400

Describe cryptococcus neoformans

Answer 400

Rare, associated with environmental contamination Can cause pulmonary infection if inhaled Can spead to CSF and cause meningitis (including deterioration in mental state) Only an issue for those who are immunodeficient Diagnosed with india ink stain and antigen in CSF and serum Treated with IV amphotericin B and fluconazole

Question 401

Describe dermatophytes

Answer 401

Cause tinea, but never invasive Diagnosed on microscopy or culture Treated with topical azoles or oral (if nail fungus)

Question 402

Describe aspergillus fumigatus

Answer 402

Widespread in rotting vegetation A rare cause of severe disease (pneumonia with necrosis) in neutropenic patients Diagnosed on microscopy and culture Treated with Amphoteracin B, azoles, or surgery

Question 403

What are some causes of fever with headache and impaired thinking?

Answer 403

Meningitis- infection of meninges and CSF with virus, bacteria or fungi. Shows CSF WBCs, bacteria/viruses. and low glucose with high protein Brain abscesses Encephalitis

Question 404

Describe syphilis and how it presents

Answer 404

It is due to T pallidum, which acts to evade the immune system by entering immune privileges sites such as the eye, brain and testes, as well as intracellular sites. Its surface is inert Much of the clinical disease is due to an immune response It causes broad anogenital ulcers with oedematous edges, a rash (palmar and soles of feet), ocular legions and neurological signs

Question 405

Describe primary syphillis

Answer 405

Initially shows a n ulcer that is solitary and painless (unless infected or treated with topical steroids etc) Shows a rubbery inguinal node Diagnose with dark field microscopy or direct fluoresent antibody

Question 406

Describe secondary syphilis

Answer 406

Appears 4-10 weeks after primary, due to haematogenous spread causing systemic symptoms Shows a rash, potentially mucous membrane lesions and alopecia

Question 407

Describe late manifestations of syphilis

Answer 407

Disease is no longer infectious, but can be reactive even though there are not always symptoms Aortic disease, optic atrophy, pyramidal signs, cognitive change and gummatous change

Question 408

What happens if syphilis infects a fetus?

Answer 408

Half undergo midtrimester abortion or perinatal death | Most changes appear at 1-2 mos of age if baby lives. 80% are not detected early

Question 409

What are some tests for syphilis>

Answer 409

EIA- a screening test seeing if there is a reaction to syphilis antigens. Pregnancy can cause a biological false positive RPR and TPPA are coagulation tests that confirm the presence of syphilis. However, false positives can still be gotten due to the presence of antibodies against other treponemal organisms (leprosy EBV)

Question 410

How is syphilis treated?

Answer 410

Can be treated with benzathene penicillin for sufferer and all contacts, or doxycycline for a penicillin allergy

Question 411

Describe genital herpes and how it presents

Answer 411

There are two strains- HSV1 (normally found in mouth) and HSV2 (normally found in genitals). In their typical locations they show a hardier resistence to treatment Transmission through mucosa, and replicates in cells of epidermis, causing destruction and inflammation. Travels via unmyelinated sensory nerves to sacral paraspinal ganglia, where it remains latent.

Question 412

How does genital herpes get transmitted and shed?

Answer 412

Transmitted by contact with a blister or ulcer, or sexual contact with someone shedding the virus. Most symptomatic infection comes from an asymptomatic partner Transmission is higher to women than to men

Question 413

How is genital herpes treated and reduced

Answer 413

Transmission is reduced by using condoms (provide 50% protection) or undergoing antiviral therapy- reduces transmission risk, acquisition etc. Treated with Aciclovir

Question 414

Describe chlamydia trachomatis

Answer 414

Presents with a transient anogenital ulcer, inguinal abscess, cervicitis, fistulae, stricture, oedema Treated for particularly i symptomatic homosexual males when rectal chlamydia NAAT is positive

Question 415

Describe anogenital warts and what can occur from them

Answer 415

Due to infection with mucosotrophic HPV Hard to treat with spontaneous regression Assoc with anogenital neoplasia and causes significant patient anxiety

Question 416

Describe the HPV virus

Answer 416

A ANA virus that needs differentiating epithelium to grow Warts are of clonal organisms Infect basal cells, where virus is uncoated, transcribed and reproduced HPV induces hyperplasia in the stratum spinosum Viral particles are assembled in the stratum corneum

Question 417

How is HPV tranmitted?

Answer 417

Common infection in the sexually active, as the virus enters sites of microtrauma Most infections are subclinical Strong evidence for perinatal (vertical) transmission HPV may be latent, subclinical or clinical

Question 418

How is HPV treated?

Answer 418

Cosmetic, or to prevent progression, pre cancerous tissue or cancer Involves physical or chemical ablation, and some drugs

Question 419

What are some complications of HPV?

Answer 419

Some can develop high grade dysplasia and cause anogenital cancer Prophylactic vaccination is now being introduced

Question 420

Describe how chemotherapy for AML can cause neutropenia

Answer 420

Chemotherapy aims to eraticate the leukaemic cell population. However, it is nonsepecific so targets any rapidly dividing cell. This results in a drop in platelets, haemoglobin, qhite blood cels and neutrophils

Question 421

Describe febrile neutropenia

Answer 421

It presents as shivering and fever, with nothing in hitory or exam to suggest the site of infection Common in neutropenic patients as they have a high rate of bacteraemia Infections arise from endogenous gut and skin flora, with a very high mortality in those with gram negative bacteraemia Outcomes are improved with empiric antibiotic treatment

Question 422

Describe the risk of bacteraemia in someone who is neutropenic

Answer 422

It is more than 1% per day with a neutrophil count of less than .1. If on it for 1 weeks, it's 33%. If on it for 6 weeks, it's about 100%

Question 423

What causes febrile bacteraemia in terms of the species responsible? How is febrile neutropenia treated?

Answer 423

Mostly streptococcus, E Coli and staph aureus Treated with empiric antibiotics, and care about IV lines etc. Eg. Tazocin (active against almost all aerobic bacteria) with gentamicin (gram negative bacilli)

Question 424

What are some strategies that can be used to prevent febrile neutropenia?

Answer 424

Nursing patient in isolation (isolation doesn't help, but filtered air and single rooms does) Giving prophylactic antibiotics (reduces risk of death but reduces resistance) Using haematopoietic growth factors to stimulate more neutrophils (shortens and reduces neutropenia, but less commonly useful in myeloid leukaemias)

Question 425

What is cystitis and how is does it present?

Answer 425

It's urinary frequency, urgency and gramping pain. | It is technically bladder inflammation

Question 426

How do we determine the cause of dysuria in men and women?

Answer 426

Women- likely to be cystitis with burning urination as STDs don't tend to affect urethra Men- need to consider urethritis due to STD as a cause. Determined by taking more of a Hx to determine cramping, urgency, frequency, discharge

Question 427

How do we diagnose and treat cystitis?

Answer 427

Do a urine dipstick to see if there are WBCs in urine (pyuria). If so, treat If there are problems, reassess and send a midstream urine sample to the lab

Question 428

What are some of the risk factors for cystitis?

Answer 428

``` Dysfunctional bladder Postmenopause (more likely to have E coli not cleared by menstruation) Sexual intercourse Past UTI Homosexual male sex Neurological disease ```

Question 429

What are the drug options for cystitis and why are they used?

Answer 429

Drugs used should be cleared by the kidneys so they get to the bladder, as well as narrow spectrum, safe and cheap Trimethoprin is 80% effective and given once a night Nitrofuratoin is 99% effective, but has to be given 4x daily

Question 430

What does trimethoprin do?

Answer 430

Interferes with folic acid synthesis, preventing bacterial replication However, this means it is NOT indicated for pregnant women

Question 431

Describe pyelonephritis and how it is treated

Answer 431

Severe flank pain radiating while passing urine, haematuria, fever, nausea, tachycardia IV treatment of gentamicin, changing to oral treatment. Watch for septic shock

Question 432

Describe the most likely causes of liver disease

Answer 432

Most likely due to chronic alcohol overuse | Viral hepatitis can be more common in other places, like in Korea

Question 433

What are the 3 main Hepatitis viruses?

Answer 433

Hep A: RNA virus, faecal oral transmission. Almost always causes acute hepatitis and is commonly asymptomatic Hep B: Blood borne, can cause acute hepatitis but rarely chronic unless in children Hep C" Blood borne, causes mostly chronic hepatitis

Question 434

Describe the hepatitis A virus

Answer 434

RNA virus diagnosed by the presence of an IgM antibody against the hep A virus. Treatment not normally required, and supportive care is adequate unless fulminant hepatitis develops (then transplant) There is a vaccine to prevent it

Question 435

Describe the hepatitis B virus and how it is diagnosed

Answer 435

It's a DNA virus that uses reverse transcriptase to convert its DNA to RNA and back again Mostly acquired through vertical transmission Illness is caused by immune activity During viral replication a large amount of HBSAg is formed, which spreads into the blood- used to diagnose current infection Surface antigen, anti HBS antibodies, core antigens are used to determine Hep B status Presence of anti hepB alone indicates vaccination Presence of surface antigen, anti-HPC, and HBEAg (replication) shows current hep B with replication, while HBEAg negative shows current hep B with no replication

Question 436

Describe how HepB is cleared or treated

Answer 436

HBEAg is often cleared by 20-30 years of age, but HBSAg clearance is uncommon Withot treatment, if an adule is infected, up to 20% will develop cirrhosis, of which up to 25% will decompensate and up to 15% well get hepatocellular cancer It can be treated with suppression- reverse transcriptase inhibitors However, some infected cells will remain for life.

Question 437

Describe hepatitis C

Answer 437

An RNA virus that doesn't incoporate into chromosomes Its nonstructural proteins form viral polymerase enzymes that are the targets of effective drugs. The HCV antibody is used to diagnose past infection Treatment has an up to 95% chance of cure, depending on virus genotype and host immunity If left, it will cause cirrhosis after 20 yers in 10%, and 2-3% will decompensate or get carcinoma in the following 5 years

Question 438

Describe the presentation of measles

Answer 438

Highly infectious disease with 2-3 days of fever, starting with conjunctivitis, coryza (runny nose), kopliks spots (mucosal membrane rash) Rash occurs days 3-7, with most unwell feeling for duration of rash Complications are common, with 10% developing a secondary infection like otitis media, pneumonia, croup Rarely it can cause encephalitis or subacute sclerosing panencephalitis

Question 439

Describe the presentation of mumps

Answer 439

Enlargements of the salivary glands, potentially causing oophoritis, orchitis, and meningoencephalitis

Question 440

Describe the presentation of meningitis in infants, and what can cause it

Answer 440

High temperature, tachycardia/pnoea, floppy neck (not stiff in infants), potential eardrum infection Can show seizures, pus in the brain, irritability as each time they are moved the spinal cord stretches Needs blood culture, immediate Rx antibiotics and CSF sample Can be caused by - strep pneumoniae- gram positive cocci - Neisseria meningitidis (appears in front of eyes)- gram negative cocci - Haempphilius influenzae (in unvaccinated infants)- gram negative bacilli (also viral agents and tuberculosis)

Question 441

Why are the causative bacteria for meningitis so dangerous for children under 2?

Answer 441

Very young children only produce very weak antibody responses to polysaccharide antigens (as these agents posess), and have poor immunological memory to these antigens

Question 442

What does the polysaccharide issue mean for vaccination of children against hameophilus B/N meningitidus/ Step pneumoniae

Answer 442

They are conjugated with a toxoid (like tetanus) and now induces antibodies to the polysaccharide protein capsule. Strep has about 10 of the 90 possible serotypes in the vaccine N meningitidis also has this type of capsule- but the B serotype has a similar capsule to that of immature human neural cells- the body has deleted lymphocytes that can produce antibodies to it, and so is immunotolerant. Therefore, we target outer membrane proteins (but this only helps short term, rather than with memory) - MenzB vaccine

Question 443

What are the different ways of classifying immunodeficiency?

Answer 443

According to the part of the immune system affected (eg. complement) Congenital- due to genetic defect/in utero disease Acquired- HIV, secondary to drug therapy, secondary to systemic disease Primary- inherited Secondary- due to other acquired factor

Question 444

How do different types of clinical presentation indicate the type of immunological deficiency?

Answer 444

Infections with - Extracellular bactiera: IgM, IgG, Complement issue, phagocyte issue - Intracellular bacteria- T cell issue, macrophage issue - Viruses: T cell issue, IgG/IgA, Complement, Interferon - Parasites- T cells, IgE Eosinophils/mast cells - Fungi- T cells, IgA, neutrophils

Question 445

When should immunodeficiency be suspected?

Answer 445

When a patient has recurrent bacterial infections, infection with unusual organisms, is taking steroids/cytotoxic drugs, has a known major systemic disease, or has lifestyle risk factors for HIV

Question 446

How do the types of CD4 T cell affect the immune response

Answer 446

Based on the person's differing levels of each, different responses may be initiated - TH1 cells will make IgM and IgG, activated TCT cells, and do better for acute viral or bacterial infection - TH2 cell produce IgG and IgE, and increase mucosal immunity. They are good for chronic infection and parasites Th17 cells make mucosal immunity and promote inflammatory processes Treg downregulate other classes

Question 447

How do checkpoint regulators affect immune responses?

Answer 447

T cell responsiveness is turned on by costimulators. These can be excitatory or inhibitory Eg. some tumour cells have surface molecules that bind to inhibitory receptors on Ct cells, preventing themselves from being killed (Notes that there are monoclonal antibodies that prevent these receptors from being activated- they result in more tumour killing, but also can result in inflammation or development of AI

Question 448

How do environmental factors affect the immune response?

Answer 448

In the last 1000 years, we have moved from being exposed to small numbers of a wide variety of antigens to being exposed to large numbers of few antigens- this causes a Treg to not be used so much, meaning we have seen an increase in AI and allergic reactions

Question 449

How do antigens and anitbody properties affect the immune reponse?

Answer 449

Foreign antigens similar to self antigens may bot stimulate a good response Our HLA types affect how an antigen is processed and if the epitope is available for recognition Antibodies present at time of antigen expose can enhance response by opsonisation, or diminish response by leading to rapid antigen removal IgG negatively feeds back on antibody production, while IgM does positive feedback

Question 450

How does the nervous system affect the immune response?

Answer 450

The HPA axis affecte the endocrine system, which releases hormones that act on the immune system Lesions in the hypothalamus depresses antibodies and vice versa Corticosteroids have profound immunosuppressive effects (and can be used clinically for AI, immunoproliferative disorders, and rejection of transplated tissue) Sex hormones diminish in vivo responses Prolactin and growth hormone elevates responses The lymph nodes are innervated in T cell rich regions- increased symp stimulation depresses antibody responses, while increasd parasymp augments antibody responses Proinflammatory cytokines also affect the nervous system esp vagus nerve, as well as having IL-1 as a neurotransmitter in preoptic and hypothalamic neurons It also increases body temp, slow wave sleep, and ilness behaviours

Question 451

How does stress affect the immune system?

Answer 451

Cases release of cortisol, ACh and norepi, reducing inflammation, immune response, and proinflammatory cytoines, leading to reduced response to infection or tissue damage

Question 452

What are the benefits of vaccination?

Answer 452

Individual gets immunity to infection | Population gets reduced transmission of infection and reduced burden in vaccinated and unvaccinated people

Question 453

What are the different types of vaccine?

Answer 453

Live attenuated vaccines- contain live viruses/bacteria, activate antibodies and CD8 Ct cells Inactivated vaccines - Whole viruses or bacteria, or fractions - Protein based vaccines, like toxicoids, subunits or subvirion - Polysaccharide based vaccines- pure cell wall polysaccharide from bacteria - Conjugate polysaccharide vaccines- cell wall linked to a protein T cell dependent antibodies are stimulated by protein antigens, while T cell independent antibodies are produced by polysaccharide antigens

Question 454

Describe live vaccines

Answer 454

Modified virus or bacteria in the lab to produce immunity but not illness Gives lifelong immunity Like MMR, tuberculosis, rotavurus (reassorted) Can cause issues in the immunocompromised

Question 455

Describe inactivated vaccines

Answer 455

Killed antigen vaccines aren't lifelong and need repeating- may be whole viral (flu, polia) or bacteria (pertussis, cholera) Fractional vaccines may be subunits (hep B) or toxicoids (diptheria, tetanus)

Question 456

Describe recombinant vaccines

Answer 456

Segment of genes into a different expression system, or engineered vaccines that replicate in places other than where they cause disease Eg. hep B

Question 457

Describe how vaccines work in childhood (brief)

Answer 457

Not live viruses until past 1 year as we cannot be sure if child is immunocompromised All are component antigen vaccines, with polysaccharides attached to proteins, or recombinants

Question 458

Describe tetaunus

Answer 458

Clostridium tetani- anaerobic, spore-forming, gram positive- penicillin sensitive. Easily introduced at time of injury, especially deep penetrating dirty wounds Causes muscular rigidity due to toxin, resulting in characteristic arching of back and lockjaw Uncommon in developed world due to shots, so elderly are most at risk

Question 459

What is neonatal tetanus?

Answer 459

Entry of toxin via umbilicus or due to incompletely immunised mother Infant has no passive immunity, and mortality rate is more than 90% Reduced incidence by giving all women of child bearing age in high risk areas three doses of toxoid

Question 460

Describe how tetanus immunisation os done

Answer 460

Passive- human or equine immunoglobulin, neutralising unbound toxin and shortens the course and improves survival- required if a dirty wound is received and there is no previous tetanus immunisation Doesn't give long term protection, and may give serum sickness

Question 461

Describe pertussis

Answer 461

Results in whooping cough- common cause of death, with highest mortality in the first year of life Deposited in the resp tract by aerosol droplets from another person's cough- very infectious Resulsts in catarrhal phase of 1-2 weeks (runny nose, conjunctivitis, malaise) Then goes on to paroxysmal phase with short expiratory burst of rapid coughing, then inspiratory gasp and whoop Convalescent phase can take weeks to months

Question 462

Describe the complications and treatment of pertussis

Answer 462

Can cause pneumonia, encephalopathy, seizures and apnoea | Treated with erythromycin- shorten illness during first few weeks but do little in established illness

Question 463

Describe pertussis vaccination

Answer 463

An acellular vaccine with a number of virulence factors-- given in 3 doses with 2 boosters Infants are at higher risk of complications Only 50% get their 3rd dose at 5 months! Need importance of timeliness

Question 464

How has the pertussis vaccine helped reduce transmission?

Answer 464

Primary vaccination and booster vaccination results in good protection/ If additional boosters are gotten, adults are not susceptible, and so then cannot infect unvaccinated or partly vaccinated infants

Question 465

Who should get the pertussis vaccine (apart from children)

Answer 465

Parents and other adults living in households with young children Adults working with children Healthcare workers, especially those working with newborns

Question 466

Describe polio and its vaccine

Answer 466

A virus that destroys lmns resulting in paralysis Affects children under five and can cause respiratory difficulty and death Oral polio vaccine used where polio is endemic. Can cause rare, vaccine associated paralytic polio disease (1/2.4 million) In NZ, we have the inactivated vaccine, which is 99% effective but more safe

Question 467

Describe hyperIgM syndrome

Answer 467

Failure to thrive with recurrent infections. Shows high IgM and low concs of other antibodies, as well as few B cells, may T and NK cells T cells don't have CD40 due to a mutation in CD40 ligand, meaning T and B cells can't communicate Only an inital immune response (with IgM) is ever formulated, with very little memory response and no class switching

Question 468

Describe effectors vs regulators in terms of the immune cells

Answer 468

Effectors- B lumphocytes, antigen specific CT cells, NK cells and ADCC cells Regulators" CD4 cells. May be TH1 (intracellular agents), TH2 (multicellular agents), Treg (downregulate responses) or TH17 (mucosal immunity and inflammation)

Question 469

Describe what antibodies vs cytotoxic T cells are useful for targeting

Answer 469

Antibodies: Extracellular antigens including virus particles (AGM), toxins (GM), exctracellular bacteria (IMG) and parasits (EA) Ct cells: Effective against intracellular antigens like virus infections, tumours and transplated organs

Question 470

How do antibodies act at mucosal surfaces?

Answer 470

Bacteria produce PAMPs, which cause local inflammation, inducing phagocytosis and complement activation Surface IgA and complement system prevents andherence and reduces mobility, enhancing destruction and phagocytosis If it breaks through the surface layer, mast cells encouter the pathogen, and recruit IgG, complement, neutrophils and eosinophils. by releasing vasoactive and chemotactic factors onto blood vessels

Question 471

Describe natural killer cells and how they are used in immunity

Answer 471

They haev CD16 receptors and CD56 surface markers When they bind to cells with down-regulated MHCclass 1 they are triggered to kill them in a similar manner to CD8 cells. This is because cells with reduced MHC I are often virus infected or tumours. They can be enhanced by IL 2 and interferon- y They can also use their Fc receptors (CD16) to bind antibodies on target cells to become ADCCs

Question 472

How are CT cells used in infection?

Answer 472

They are important in pathogens with an intracellular cytoplasmic phase, and are therefore important in resolving viral infections, as they are activated by interferons rather than cytokines Antibodies produced for viral infections are only usefu in repeat infection

Question 473

What are the different types of pro-inflammatory cytokines used in infection and what are their purposes?

Answer 473

Pro-inflammatory cytokines are important in early processes by promoting inhibition, inactivation and removal of pathogens. They are also involved in temperature regulation (fever production) and behavioural changes, as well as promoting tissue repair, and activating T and B cells TNFa is good against bacteria, esp gram negative. Release is triggered by lipopolysaccharide, in bacterial cell walls IL1 is similar but doesn't help with tumour necrosis IL6 is for the acute phase reponse- adjustment of plasma proteins to respond to injury or infection. They may also perform opsonisation or help with blood clotting

Question 474

Describe chemokines and interferons and how they are used in inflammation

Answer 474

Chemokines- aid chemotaxis Interferons- important antivirals. there are gamma, produced by TH cells, as well as a ad B types, induced in most cells that undergo viral infection to induce a transient antiviral state in nearby cells by inducing cleavage of viral RNA by intracellular enzymes

Question 475

What are some common healthcare associated infections and what may cause them?

Answer 475

Risk of pneumonia as patient may have been ventilated or may not be breathing well Risk of UTI from catheters Risk of bacteraemia or sepsis from cannulas etc

Question 476

Dscribe what a biofilm is and how it can affect healthcare associated infection

Answer 476

An organised community of bacteria that produce ECM and protein Different bacteria have different roles, and they commonly occur on hte surfaces of devices. They are hard to treat! This is because they are often dormant, and most antibiotics target bacteria that are proliferating The bacteria deeper into the biofilm are more difficult to reach They all may have different gene expressions and can change their cell surface properties Resistance is difficult to gague Specialized survivor cells resistant to antibiotics may also be present

Question 477

Describe the factors that affect the development of a biofilm

Answer 477

Bacterial factors- hydrophobicity, electrostatic force, MSCRAMMS and polysaccharide intracellular adhesion Device factors include material used (PVC worst, silicon best), synthetic material worse, textured or irregular surfaces provide more likely sites Those with a longer duration in the body are more likely to become infected Its placement technique is also important

Question 478

What are common bacteria that cause device associated infection?

Answer 478

Staph epidermidis, staph aureus, e. coli. Fungi may be candida

Question 479

How do you treat and prevent device infections?

Answer 479

Treatment: Note infection site and swab pus, or culture blood- from the part of device internal, not the skin! The device must be removed if purulent Prevent by only using and keeping necessary devices, appropriate placement, hadnwashing and monitoring

Question 480

What is nosocomial diarrhoea and how does it develop?

Answer 480

Results from clostridium difficile infection after broad spectrum antibiotics. Results in explosive, watery bloodless diarrhoea that

Question 481

Describe how clostridium difficile infects the gut

Answer 481

It is part of the normal gut flora, but produces endospores that are dormant and antibiotic resistant wWhen broad antibiotics are given, all of the flora apart from the spores are wiped out, allowing C difficile to out compete the other kinds of bacteria when treatment is stopped.

Question 482

What are the consequences of c difficile infection?

Answer 482

It produces toxin A and B. These are endocytosed by the gut mucosa, and cause collapse of the cytoskeleton and depolymerization of actin Toxin A causes apoptosis, allowing toxin B and other bacteria to get into the wall of the gut. At end stage it can lead to toxic megacolon, where the barrier is near useless and likely to perforate

Question 483

How do you diagnose and treat c dificile?

Answer 483

Diagnosed on unformed stool and gram staining, and antibody based assays for toxins and cell surface antigens Treated by discontinuing predisposing antibiotic and giving metronidazole or vancomycin, and supporting fluid loss and pain

Question 484

What are risk factors for C difficile?

Answer 484

Hospital patients on antibiotics, longer than 1 week in hospital and treatments that disrupt the gut flora

Question 485

How can we prevent C difficile?

Answer 485

Paying attention to hygiene, antibiotic stewardship, autoclaving and sporicidal cleaners.

Question 486

What are some examples of infections more likely to be contracted in developing countries?

Answer 486

From contaminated water and food (human or animal feces)- Salmonella typhi/enteritidis, campylobacter jejuni, Hep A From infected vectors: Malaria, dengue fever

Question 487

What are the two main types of malaria and what is their vector?

Answer 487

Plasmodium falciparum (potentially fatal) and plasmodium vivax (benign). These are protozoa transmitted by the anopheles mosquito